Rare Cancer News & Clinical Trials » Adrenal Gland Cancer

Adrenal Gland Cancer (566 unread)

Agnostic Therapy in Rare Solid Tumors

Posted: October 14th, 2024, 11:00pm UTC

Conditions: Urachal Cancer; Parathyroid Carcinoma; Fibrolamellar Carcinoma; Angiosarcoma; Secretory Carcinoma of Breast; Anal Neoplasms; Metaplastic Breast Carcinoma; Translocation Renal Cell Carcinoma; Carcinosarcoma; Small Intestine Neoplasms; Cholangiocarcinoma; Sertoli-Leydig Cell Tumor; Adenoid Cystic Carcinoma; Mesothelioma; Neuroblastoma; Adrenal Gland Neoplasms; Penile Neoplasms; Apocrine Carcinoma; Fibrosarcoma; Cancer of Unknown Primary; Hemangioblastoma; Thyroid Neoplasms; Hepatoblastoma; Fallopian Tube Neoplasms; Leiomyosarcoma; Vaginal Neoplasms; Neurofibrosarcoma; Gallbladder Neoplasms; Osteosarcoma; Biliary Tract Neoplasms; Clear Cell Endometrial Cancer; Yolk Sac Tumor; Vulvar Neoplasms; Kaposi Sarcoma; Ovarian Epithelial Cancer; Soft Tissue Sarcoma; Urethral Neoplasms; Granulosa Cell Tumor; Primitive Neuroectodermal Tumor; Neuroendocrine Tumors; Trophoblastic Tumor
Interventions: Drug: Nivolumab
Sponsors: Instituto do Cancer do Estado de SÃ£o Paulo; Financiadora de Estudos e Projetos
Recruiting

SCINTIX [BgRT} Using RMRS in Solid and Soft Tissue Tumors

Posted: October 10th, 2024, 11:00pm UTC

Conditions: Thoracic Cancer; Head and Neck Cancer; Pelvic Cancer; Hepatobiliary Carcinoma in Situ; Retroperitoneal Cancer; Distributed and Orphan Tumors
Interventions: Device: RefleXion X1 Radiotherapy System [Imaging Only]
Sponsors: RefleXion Medical
Not yet recruiting

Atovaquone Combined with Radiation in Children with Malignant Brain Tumors

Posted: October 3rd, 2024, 11:00pm UTC

Conditions: High-grade Glioma; Medulloblastoma; Diffuse Intrinsic Pontine Glioma; Diffuse Midline Glioma, H3 K27M-Mutant
Interventions: Drug: Atovaquone; Radiation: Radiation Therapy
Sponsors: Emory University; Morningside Foundation/Peach Bowl LegACy Fund
Recruiting

Permalink for 'Trial for Local Ablative Treatment (LAT) Optimization in Patients With Advanced Non-Small Cells Lung Cancer (NSCLC) Presenting an Anaplastic Lymphoma Kinase (ALK) Rearrangement Treated by Brigatinib'

Trial for Local Ablative Treatment (LAT) Optimization in Patients With Advanced Non-Small Cells Lung Cancer (NSCLC) Presenting an Anaplastic Lymphoma Kinase (ALK) Rearrangement Treated by Brigatinib

Posted: October 1st, 2024, 11:00pm UTC

Conditions: NSCLC
Interventions: Biological: Blood samples for Hematology; Biological: Blood samples for Chemistry; Biological: Blood sample for liver function tests; Biological: Pregnancy test; Procedure: Tumour assessment; Procedure: Local Ablative Therapy (LAT)
Sponsors: Groupe Francais De Pneumo-Cancerologie
Not yet recruiting

Brain Irradiation for Childhood Cancer - Endocrine Monitoring During the First Years

Posted: September 30th, 2024, 11:00pm UTC

Conditions: Endocrine; Deficiency; Hypothalamo-Pituitary Disorder; Radiotherapy Side Effect
Interventions: Radiation: Blood sample, urine sample, osteodensitometry
Sponsors: University Hospital, Angers
Not yet recruiting

Mid-transverse Process Combined With Erector Spinae Block Versus Paravertebral Plane Block

Posted: September 30th, 2024, 11:00pm UTC

Conditions: Lung Cancer
Interventions: Procedure: Mid-transverse process to pleura block combined with erector spinae block; Procedure: paravertebral block
Sponsors: Cairo University
Not yet recruiting

Pathological Typeï¼ŒGene Mutation and Clinical Characteristics of Unilateral Primary Aldosteronism

Posted: September 19th, 2024, 11:00pm UTC

Conditions: Primary Aldosteronism
Interventions: Other: Tissue specimens were stained by histopathology of hematoxylin-eosin
Sponsors: Qifu Li
Recruiting

Permalink for 'To Quantify the Impact of Addition of the GAAD Score to Imaging in Patients with Chronic Liver Disease Eligible for HCC Surveillance.'

To Quantify the Impact of Addition of the GAAD Score to Imaging in Patients with Chronic Liver Disease Eligible for HCC Surveillance.

Posted: September 19th, 2024, 11:00pm UTC

Conditions: Cancer, Hepatocellular
Interventions: Diagnostic Test: GAAD score
Sponsors: Erasmus Medical Center
Recruiting

Phase II Study of PD-1 Antibody Combined with Radiotherapy in Recurrent or Metastatic Adrenal Cortical Carcinoma

Posted: September 9th, 2024, 11:00pm UTC

Conditions: Adrenocortical Carcinoma
Interventions: Drug: Triprolizumab; Device: rodiotherapy
Sponsors: Sun Yat-sen University
Not yet recruiting

A Randomized Clinical Trial About Use of 3D Laparoscopy Versus 2D Laparoscopy in Adrenal Surgery

Posted: August 28th, 2024, 11:00pm UTC

Conditions: Adrenal Mass; Adrenal Adenoma; Adrenal Gland Neoplasms
Interventions: Procedure: laparoscopic adrenalectomy
Sponsors: University of Palermo
Completed

Institutional Registry of Rare Diseases

Posted: August 27th, 2024, 11:00pm UTC

Conditions: Rare Diseases; Amyloidosis; Sarcoidosis; Phacomatosis; Pheochromocytoma; Paraganglioma; Von Hippel-Lindau Disease; Immunoglobulin G4-Related Disease; Demyelinating Diseases; Inborn Errors of Metabolism; Eosinophilic Gastrointestinal Disorders; Hypertrophic Cardiomyopathy; Gaucher Disease; Congenital Adrenal Hyperplasia; Hereditary Angioedema; Pulmonary Hypertension; Wilson Disease; Vascular Anomalies; Mastocytosis; Multiple Endocrine Neoplasia; Inflammatory Bowel Diseases; Prader-Willi Syndrome; Hirschsprung Disease; Cushing Syndrome
Sponsors: Hospital Italiano de Buenos Aires
Recruiting

Testicular Adrenal Rest Tumor in Congenital Adrenal Hyperplasia Patients Attending Assuit University Children Hospital

Posted: August 21st, 2024, 11:00pm UTC

Conditions: Testicular Adrenal Rest Tumor; Congenital Adrenal Hyperplasia
Sponsors: Assiut University
Not yet recruiting

Permalink for 'A Randomized Controlled Trial to Assess the Impact of Live and Recorded Music-Based Interventions on Pre-operative Stress, Mood, Pain and Biomarkers, in Neurosurgical Patients (Music-STAR Trial)'

A Randomized Controlled Trial to Assess the Impact of Live and Recorded Music-Based Interventions on Pre-operative Stress, Mood, Pain and Biomarkers, in Neurosurgical Patients (Music-STAR Trial)

Posted: August 5th, 2024, 11:00pm UTC

Conditions: Stress; Pain
Interventions: Other: Steinway Spirio M recording/player piano
Sponsors: M.D. Anderson Cancer Center
Not yet recruiting

Cadonilimab With Chemoradiation for Recurrent and Oligometastatic Endometrial Carcinoma

Posted: August 1st, 2024, 11:00pm UTC

Conditions: Endometrial Neoplasms; Neoplasm Recurrence, Local; Neoplasm Metastasis
Interventions: Drug: Paclitaxel and Cisplatin; Drug: Cadonilimab; Radiation: Radiotherapy
Sponsors: Shandong Cancer Hospital and Institute
Recruiting

Effect of a GnRH Analog on Hepatic Steatosis

Posted: July 26th, 2024, 11:00pm UTC

Conditions: Metabolic Dysfunction-Associated Steatotic Liver Disease; Nonalcoholic Fatty Liver; Endometriosis
Interventions: Drug: Goserelin Acetate 3.6 mg inj, implant
Sponsors: Aristotle University Of Thessaloniki; 424 General Military Hospital
Not yet recruiting

CRISAL Study:Cancer Risk In Secreting Adrenal Lesions

Posted: July 25th, 2024, 11:00pm UTC

Conditions: Adrenal Tumor; Adrenal Incidentaloma; Surgery
Sponsors: University of Roma La Sapienza
Recruiting

Impact of Antihypertensive Therapy on Recurrence Risk of Ovarian Cancer for Bevacizumab-associated Hypertension

Posted: July 23rd, 2024, 11:00pm UTC

Conditions: Ovarian Cancer; Antiangiogenic-Associated Hypertension; Adjuvant Bevacizumab; Hypertension
Interventions: Drug: arm A - angiotensin converting enzyme inhibitors (ACEi); Drug: arm B - calcium channel blockers (CCBs); Drug: arm R - angiotensin receptor blockers ARB
Sponsors: Groupe Hospitalier Pitie-Salpetriere; Dr Floriane Jochum, Principal Investigator; Institut Curie
Active, not recruiting

18F-Fibroblast Activation Protein Inhibitor ([18F]FAPI-74) PET Imaging for Cancer Detection

Posted: July 16th, 2024, 11:00pm UTC

Conditions: Pancreatic Ductal Adenocarcinoma; Cholangiocarcinoma; Gastric Cancer; Bladder Cancer; Hepatocellular Carcinoma; Pheochromocytoma; Ovarian Cancer
Interventions: Drug: [18F]FAPI-74; Drug: [18F]FDG
Sponsors: National Cancer Institute (NCI)
Not yet recruiting

The Plasma Metabolomics Profiling of Primary Aldosteronism

Posted: July 15th, 2024, 11:00pm UTC

Conditions: Primary Aldosteronism; Essential Hypertension; Idiopathic Aldosteronism; Aldosterone-producing Adenoma
Interventions: Diagnostic Test: liquid chromatography-mass spectrometry (LC/MS)
Sponsors: Third Military Medical University
Completed

Probiotics for Depression in Cancer Patients

Posted: July 11th, 2024, 11:00pm UTC

Conditions: Depression; Anxiety Disorder; Probiotics; Gastrointestinal Cancer; Quality of Life; Chemotherapy
Interventions: Dietary Supplement: Psychobiotics; Other: Placebo
Sponsors: Aristotle University Of Thessaloniki
Recruiting

Study of Preoperative Radiation Therapy in Participants With Resectable Recurrent Abdominal Adrenocortical Carcinoma

Posted: July 4th, 2024, 11:00pm UTC

Conditions: Adrenocortical Carcinoma (ACC); Recurrent Adrenocortical Carcinoma (ACC); Recurrent Abdominal Adrenocortical Carcinoma (ACC); Carcinoma, Adrenocortical; Carcinoma, Adrenal Cortical
Interventions: Radiation: Preoperative external beam radiation therapy (EBRT); Procedure: Surgical resection
Sponsors: National Cancer Institute (NCI)
Not yet recruiting

A Giant Myelolipoma.

Posted: June 28th, 2024, 11:00pm UTC

Conditions: Adrenal Myelolipoma
Interventions: Procedure: laparoscopic adrenalectomy
Sponsors: Instituto Mexicano del Seguro Social
Completed

Permalink for '[212Pb]VMT-Alpha-NET in Metastatic or Inoperable Somatostatin-Receptor Positive Gastrointestinal Neuroendocrine Tumors, Pheochromocytoma/Paragangliomas, Small Cell Lung, Renal Cell, and Head and Neck Cancers'

[212Pb]VMT-Alpha-NET in Metastatic or Inoperable Somatostatin-Receptor Positive Gastrointestinal Neuroendocrine Tumors, Pheochromocytoma/Paragangliomas, Small Cell Lung, Renal Cell, and Head and Neck Cancers

Posted: June 28th, 2024, 11:00pm UTC

Conditions: Head and Neck Tumors; Kidney Cancers; Small Cell Lung Cancers; Pheochromocytoma/Paragangliomas; Gastrointestinal Neuroendocrine Tumors; Somatostatin Receptor Positive
Interventions: Drug: 68Ga-DOTATATE; Drug: [203Pb]VMT-alpha-NET; Drug: [212Pb]VMT-alpha-NET
Sponsors: National Cancer Institute (NCI)
Not yet recruiting

Synergistic Effects of PD-1 Antibody and Chemotherapy Followed by Surgery in Limited-metastatic G/GEJ Adenocarcinoma

Posted: June 21st, 2024, 11:00pm UTC

Conditions: Gastric Cancer; GastroEsophageal Cancer
Interventions: Procedure: Radical surgery; Drug: PD-1 Monoclonal Antibody; Drug: XELOX Chemotherapy Regimen; Procedure: Local Treatment
Sponsors: Shanghai Zhongshan Hospital
Not yet recruiting

Permalink for 'The Incidence and Outcomes of Metabolically Active Brown Adipose Tissue (aBAT) in Patients With Pheochromocytoma or Paraganglioma (PPGLs)'

The Incidence and Outcomes of Metabolically Active Brown Adipose Tissue (aBAT) in Patients With Pheochromocytoma or Paraganglioma (PPGLs)

Posted: June 3rd, 2024, 11:00pm UTC

Conditions: Pheochromocytoma; Paraganglioma
Interventions: Diagnostic Test: FDG-PET Scan
Sponsors: King's College Hospital NHS Trust
Recruiting

Permalink for 'Study of the Value of hPG80 (Circulating Progastrin) for the Diagnosis of Neuroendocrine Tumours in Patients With an MEN1 Mutation'

Study of the Value of hPG80 (Circulating Progastrin) for the Diagnosis of Neuroendocrine Tumours in Patients With an MEN1 Mutation

Posted: May 27th, 2024, 11:00pm UTC

Conditions: Neuroendocrine Tumors; MEN1 Mutation
Interventions: Biological: blood sample
Sponsors: Centre Hospitalier Universitaire Dijon
Recruiting

Permalink for 'Somatostatin-Receptors (SSTR)-Agonist [212Pb]VMT-alpha-NET in Metastatic or Inoperable SSTR+ Gastrointestinal Neuroendocrine Tumor and Pheochromocytoma/Paraganglioma Previously Treated With Systemic Targeted Radioligand Therapy'

Somatostatin-Receptors (SSTR)-Agonist [212Pb]VMT-alpha-NET in Metastatic or Inoperable SSTR+ Gastrointestinal Neuroendocrine Tumor and Pheochromocytoma/Paraganglioma Previously Treated With Systemic Targeted Radioligand Therapy

Posted: May 24th, 2024, 11:00pm UTC

Conditions: Somatostatin Receptor Positive; Gastrointestinal Neuroendocrine Tumors; Pheochromocytoma; Paragangliomas
Interventions: Drug: 68Ga-DOTATATE; Drug: [203Pb]VMT-alpha-NET; Drug: [212Pb]VMT-alpha-NET
Sponsors: National Cancer Institute (NCI)
Not yet recruiting

A Study of Lower Radiotherapy Dose to Treat Children With CNS Germinoma

Posted: April 16th, 2024, 11:00pm UTC

Conditions: Basal Ganglia Germinoma; Central Nervous System Germinoma; Diabetes Insipidus; Pineal Region Germinoma; Suprasellar Germinoma; Thalamic Germinoma
Interventions: Radiation: 3-Dimensional Conformal Radiation Therapy; Procedure: Biospecimen Collection; Drug: Carboplatin; Drug: Etoposide; Radiation: Intensity-Modulated Radiation Therapy; Procedure: Lumbar Puncture; Procedure: Magnetic Resonance Imaging; Other: Questionnaire Administration; Procedure: Surgical Procedure
Sponsors: Children's Oncology Group
Recruiting

Complex Exploratory Study of Alcohol-Associated Hepatitis

Posted: April 10th, 2024, 11:00pm UTC

Conditions: Alcoholic Hepatitis
Sponsors: Pavol Jozef Safarik University; L Pasteur University Hospital; Hospital Agel Kosice-Saca; Technical University in Kosice; Western University; University of Roma La Sapienza
Not yet recruiting

Sphenopalatine Ganglion Block for Postop Pain Management

Posted: April 9th, 2024, 11:00pm UTC

Conditions: Pituitary; Pain, Postoperative
Interventions: Drug: Bupivacaine-Epinephrine 0.5%-1:200,000 Injectable Solution; Drug: Placebo
Sponsors: Hamilton Health Sciences Corporation
Not yet recruiting

$Permalink for 'Talquetamab in Combination With Iberdomide and Dexamethasone for Relapsed or Refractory Multiple Myeloma'$

Talquetamab in Combination With Iberdomide and Dexamethasone for Relapsed or Refractory Multiple Myeloma

Posted: April 4th, 2024, 11:00pm UTC

Conditions: Multiple Myeloma; Refractory Multiple Myeloma; Relapsed Multiple Myeloma
Interventions: Biological: Talquetamab; Drug: Iberdomide; Drug: Dexamethasone; Procedure: Bone Marrow Biopsy
Sponsors: Thomas Martin, MD; Bristol-Myers Squibb; Janssen Research & Development, LLC
Not yet recruiting

Detecting Mild Autonomous Cortisol Secretion in Patients With Adrenal Incidentaloma

Posted: April 3rd, 2024, 11:00pm UTC

Conditions: Mild Autonomous Cortisol Secretion (MACS)
Interventions: Diagnostic Test: Various labs and imaging tests
Sponsors: The Cleveland Clinic; Recordati Rare Diseases
Not yet recruiting

Phase 1 Study Evaluating Safety and Tolerability of SL-T10, GX-I7, and Pembrolizumab Triple Combination in mCRPC.

Posted: April 3rd, 2024, 11:00pm UTC

Conditions: Metastatic Castration-resistant Prostate Cancer (mCRPC)
Interventions: Biological: SL-T10; Biological: GX-I7; Biological: Pembrolizumab
Sponsors: SL VAXiGEN
Recruiting

The Optimal Number of Fiducial Marker for Stereotactic Body Radiotherapy

Posted: April 2nd, 2024, 11:00pm UTC

Conditions: Lung Cancer; Liver Cancer; Pancreatic Cancer; Renal Cell Carcinoma
Interventions: Radiation: SBRT
Sponsors: Peking University Third Hospital
Recruiting

Dostarlimab for Locally Advanced or Metastatic Cancer (Non-colorectal/Non-endometrial) With Tumor dMMR/MSI

Posted: March 27th, 2024, 11:00pm UTC

Conditions: Pancreatic Adenocarcinoma; Ampulla of Vater Carcinoma; Adrenocortical Carcinoma; Neuroendocrine Carcinoma; Soft Tissue Sarcoma; Small Bowel Adenocarcinoma; Duodenum Adenocarcinoma; Gastric Adenocarcinoma
Interventions: Drug: Dostarlimab; Drug: Chemotherapy
Sponsors: UNICANCER; National Cancer Institute, France; GlaxoSmithKline
Recruiting

Side-specific Factors for Conversion in Adrenalectomy for Pheochromocytoma.

Posted: March 26th, 2024, 11:00pm UTC

Conditions: Adrenal Tumor
Interventions: Procedure: laparoscopic right adrenalectomy
Sponsors: Zagazig University
Completed

Misoprostol Versus Oxytocin Infusion On Reducing Blood Loss During Abdominal Myomectomy

Posted: March 22nd, 2024, 11:00pm UTC

Conditions: Myoma;Uterus
Interventions: Drug: Misoprostol 200mcg Tab; Drug: Oxytocin
Sponsors: Cairo University
Recruiting

The Efficacy of Combining Platelet-rich Plasma With Crystallized Phenol in Pilonidal Sinus Disease

Posted: March 22nd, 2024, 11:00pm UTC

Conditions: Pilonidal Sinus
Interventions: Procedure: crystallized phenol + platelet rich plasma application; Procedure: crystallized phenol
Sponsors: Necmi KadÄ±oÄŸlu Hospital
Recruiting

Permalink for 'Neuroendocrine Mechanisms in Adiposity: An Integrated Approach to the Characterization of Potential Pharmacological Novel Targets Based on Experimental and Clinical Models'

Neuroendocrine Mechanisms in Adiposity: An Integrated Approach to the Characterization of Potential Pharmacological Novel Targets Based on Experimental and Clinical Models

Posted: March 22nd, 2024, 11:00pm UTC

Conditions: Endocrine Disorders; Adiposity; Pituitary Adenoma; Cushing Syndrome; Acromegaly; Hypopituitarism
Sponsors: IRCCS San Raffaele
Not yet recruiting

Targeting Chronic Stress for Reducing Risk Factors for Colorectal Cancer

Posted: March 21st, 2024, 11:00pm UTC

Conditions: Mindfulness; Colon Cancer; Females
Interventions: Behavioral: Mindfulness
Sponsors: University of Illinois at Chicago
Recruiting

Physical Attendance Versus Telephone or Video Follow-up in Patients With Non-functioning Pituitary Tumors.

Posted: March 7th, 2024, 1:00am UTC

Conditions: Non-Functional Pituitary Adenoma
Interventions: Behavioral: Telephone-/video follow-up; Behavioral: In-person follow-up
Sponsors: Zealand University Hospital
Not yet recruiting

Adrenal Project: Clinical and Epidemiological Characterization of Adrenocortical Carcinoma in a Brazilian Cohort

Posted: February 28th, 2024, 1:00am UTC

Conditions: Carcinoma Adrenal; Carcinoma, Adrenocortical Recurrent
Sponsors: Latin American Cooperative Oncology Group
Not yet recruiting

Prophylactic Double Thermal Ablation After Endoscopic Mucosal Resection of Large Non-Pedunculated Colorectal Polyps

Posted: February 22nd, 2024, 1:00am UTC

Conditions: Colorectal Cancer; Polyp of Colon
Interventions: Procedure: Hybrid Argon Plasma Coagulation (h-APC); Procedure: Snare tip soft coagulation (STSC)
Sponsors: Centre hospitalier de l'UniversitÃ© de MontrÃ©al (CHUM)
Recruiting

Effects of Erector Spina Plan Block and Epidural Analgesia in Whipple Surgery

Posted: February 12th, 2024, 1:00am UTC

Conditions: Pancreatic Cancer
Sponsors: Ankara City Hospital Bilkent
Completed

A Single Center Randomized Controlled Study on the Promotion of Rapid Recovery

Posted: February 9th, 2024, 1:00am UTC

Conditions: Nonfunctional Adrenal Cortex Adenoma; Primary Aldosteronism; Cushing Syndrome
Interventions: Procedure: Tubeless laparoscopic adrenalectomy; Procedure: Drainage tube
Sponsors: Zhe Meng
Recruiting

Evaluating the Functional Status of the Adrenal Glands With [68Ga]Ga-PentixaFor in Hyperaldosteronism and Hypercortisolism

Posted: February 7th, 2024, 1:00am UTC

Conditions: Hyperaldosteronism; Hypercortisolism; Cushing s Syndrome
Interventions: Drug: [68Ga]Ga-PentixaFor
Sponsors: National Cancer Institute (NCI)
Recruiting

Exercise Intensity on Brain & Mental Health in Stress

Posted: February 7th, 2024, 1:00am UTC

Conditions: Healthy Adults; Adults With Stress-related Symptoms
Interventions: Behavioral: Seated rest; Behavioral: Exercise at moderate intensity; Behavioral: Exercise at vigorous intensity
Sponsors: The Swedish School of Sport and Health Sciences; The Knowledge Foundation; Avonova; SATS; Itrim
Not yet recruiting

Susceptibility to Infectious Diseases in obEsity: an endocRine trAnslational socioLogic Evaluation, "SIDERALE"

Posted: February 1st, 2024, 1:00am UTC

Conditions: Obesity; Type2diabetes; Lipodystrophy; Infections; Obesity Associated Disorder
Interventions: Dietary Supplement: Mediterranean diet; Dietary Supplement: Melatonin supplementation
Sponsors: Federico II University; University of Roma La Sapienza; University of Pisa; UniversitÃ degli Studi del Piemonte Orientale "Amedeo Avogadro"; University of Rome Foro Italico
Recruiting

Comparison of Catecholamine Concentrations in Venous Blood During Selective Adrenal Artery Embolization

Posted: January 29th, 2024, 1:00am UTC

Conditions: Resistant Hypertension; Secondary Hypertension; Secondary Hypertension to Endocrine Disorders; Primary Aldosteronism
Interventions: Procedure: Selective adrenal artery embolization
Sponsors: First Affiliated Hospital of Chengdu Medical College
Recruiting

Development of Clinical Evidence for Optimal Management of Adrenal Diseases Based on Real-World Data

Posted: January 29th, 2024, 1:00am UTC

Conditions: Adrenal Tumor; Primary Aldosteronism; Cushing Syndrome; Pheochromocytoma; Adrenal Cortical Carcinoma
Sponsors: Seoul National University Hospital; Asan Medical Center; Seoul National University Bundang Hospital; Samsung Medical Center; Inha University Hospital; Chonnam National University Hospital; Nowon Eulji Medical Center
Recruiting

Cognitive Functioning and Health Related Quality of Life in Retinoblastoma Survivors

Posted: January 29th, 2024, 1:00am UTC

Conditions: Retinoblastoma; Neurocognitive Dysfunction; Health-Related Behavior
Interventions: Diagnostic Test: Neuropsychological assesment; Diagnostic Test: Psychosocial functioning and quality of life (questionnaires); Diagnostic Test: Parental psychosocial functioning (questionnaires)
Sponsors: Amsterdam University Medical Center
Enrolling by invitation

A Study of Participants With Cerebral Adrenoleukodystrophy (CALD) Treated With Elivaldogene Autotemcel

Posted: January 25th, 2024, 1:00am UTC

Conditions: Cerebral Adrenoleukodystrophy (CALD)
Interventions: Other: No Intervention
Sponsors: bluebird bio; Center for International Blood and Marrow Transplant Research
Recruiting

Hemodynamic Instability of Patient With Spontaneous Subarachnoid Hemorrhage

Posted: January 23rd, 2024, 1:00am UTC

Conditions: Subarachnoid Hemorrhage, Spontaneous; Subarachnoid Hemorrhage, Aneurysmal
Interventions: Diagnostic Test: biomarkers
Sponsors: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Recruiting

Effect of HIFU on Sleep Quality Measures in Obese Doubled Chin Women

Posted: January 22nd, 2024, 1:00am UTC

Conditions: OBESITY
Interventions: Device: high intensity focused ultrasound; Other: Doubled chin exercises
Sponsors: Cairo University
Recruiting

The NADage Study: Nicotinamide Riboside Replenishment Therapy Against Functional Decline in Aging

Posted: January 17th, 2024, 1:00am UTC

Conditions: Frailty; Frail Elderly Syndrome; Frailty Syndrome; Aging
Interventions: Dietary Supplement: Nicotinamide Riboside (NR); Other: Placebo
Sponsors: Haukeland University Hospital
Not yet recruiting

Stereotactic Ablative Radiotherapy in Synchronous and Metachronous Oligo-Metastatic Non Small Cell Lung Cancer

Posted: January 15th, 2024, 1:00am UTC

Conditions: NSCLC; NSCLC Stage IV; Oligometastatic Disease; Non Small Cell Lung Cancer; Non Small Cell Lung Cancer Metastatic; EGF-R Positive Non-Small Cell Lung Cancer; NSCLC Stage IV Without EGFR/ALK Mutation; Non-Small Cell Adenocarcinoma; Non-Small Cell Squamous Lung Cancer; Non-Small Cell Lung Cancer With Mutation in Epidermal Growth Factor Receptor; Synchronous Metastases; Metachronous Metastasis
Interventions: Radiation: Stereotactic Ablative Radiotherapy
Sponsors: Radiotherapy Oncology Centre "Santa Maria" Hospital; Paola Anselmo,MD; Michelina Casale,PhD; Fabio Trippa,MD
Recruiting

Permalink for 'Local Therapy for Oligometastatic Esophageal Squamous Cell Cancer Patients Treated With PD-1 Inhibitor: a Prospective, Randomized, Phase III Clinical Trial.'

Local Therapy for Oligometastatic Esophageal Squamous Cell Cancer Patients Treated With PD-1 Inhibitor: a Prospective, Randomized, Phase III Clinical Trial.

Posted: January 4th, 2024, 1:00am UTC

Conditions: Esophageal Squamous Cell Carcinoma; Oligometastatic Disease; Radiotherapy
Interventions: Combination Product: PD-1 inhibitor+/- chemotherapy combined with local therapy; Drug: systemic therapy alone
Sponsors: Fudan University
Recruiting

Upfront EUS CGN/CPN vs Conventional Step up Approach for Inoperable Painful Pancreatic Cancer

Posted: December 7th, 2023, 1:00am UTC

Conditions: Pancreatic Cancer Non-resectable; Tumor Pancreas; Pain Cancer
Interventions: Procedure: EUS-guided coeliac ganglion neurolysis / celiac plexus neurolysis
Sponsors: Chinese University of Hong Kong
Recruiting

Treatment of Advanced Endocrine Tumor With Iindividualized mRNA Neoantigen Vaccine (mRNA-0523-L001)

Posted: November 21st, 2023, 1:00am UTC

Conditions: Adrenal Cortical Carcinoma; Medullary Thyroid Cancer; Thymic Neuroendocrine Carcinoma; Pancreatic Neuroendocrine Tumor
Interventions: Biological: individualized mRNA neoantigen vaccine (mRNA-0523-L001)
Sponsors: Shanghai Jiao Tong University School of Medicine
Recruiting

Metastasis-directed Therapy for Oligometastases of Breast Cancer

Posted: November 16th, 2023, 1:00am UTC

Conditions: Breast Cancer; Oligometastasis; Metastatic Breast Cancer
Interventions: Drug: Systemic therapy for 12 weeks after primary registration; Procedure: Radiation therapy (SBRT/conventional RT); Procedure: Surgery; Drug: Same systemic therapy after secondary registration
Sponsors: Tokyo Medical and Dental University
Recruiting

Post-Operative Dosing of Dexamethasone in Patients With Brain Tumors After a Craniotomy, PODS Trial

Posted: November 15th, 2023, 1:00am UTC

Conditions: Low Grade Glioma; Malignant Brain Glioma; Malignant Brain Neoplasm; Meningioma
Interventions: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Dexamethasone; Procedure: Magnetic Resonance Imaging; Other: Questionnaire Administration
Sponsors: Emory University; National Cancer Institute (NCI)
Not yet recruiting

Water and Electrolytes Content in HYpertension (WHYSKI) in the SKIn

Posted: October 19th, 2023, 11:00pm UTC

Conditions: Hyperaldosteronism; Hypertension; Aldosterone-producing Adenoma; Aldosteronism; Aldosterone Disorder; Essential Hypertension; Bilateral Adrenal Hyperplasia; Conn Adenoma
Interventions: Procedure: Skin Biopsy; Procedure: Video-laparoscopic adrenalectomy
Sponsors: University Hospital Padova
Recruiting

Study of Radiotherapy and Pembrolizumab in People With Adrenocortical Carcinoma

Posted: October 4th, 2023, 11:00pm UTC

Conditions: Adrenocortical Carcinoma; ACC; Metastatic Adrenocortical Carcinoma
Interventions: Radiation: Ablative Radiotherapy; Drug: Pembrolizumab
Sponsors: Memorial Sloan Kettering Cancer Center
Recruiting

Tranexamic Acid in Nasal Mohs Reconstruction

Posted: September 28th, 2023, 11:00pm UTC

Conditions: Postoperative Bleeding; Skin Cancer Face
Interventions: Drug: Treatment (tranexamic acid and 1% lidocaine with 1:100,000 epinephrine); Drug: Control (1% lidocaine with 1:100,000 epinephrine)
Sponsors: Vanderbilt University Medical Center
Recruiting

MT2022-01: MSCs for ALD

Posted: September 11th, 2023, 11:00pm UTC

Conditions: Cerebral Adrenoleukodystrophy
Interventions: Biological: Mesenchymal stem cells (IV-MSC)
Sponsors: Masonic Cancer Center, University of Minnesota
Suspended

Core Stabilization Exercise Therapy in Chronic Lower Back Back Management in Community Dwelling Older Adults

Posted: September 8th, 2023, 11:00pm UTC

Conditions: Chronic Low-back Pain; Older Adults; Core Stabilization Exercise Therapy
Interventions: Behavioral: core stabilization exercise
Sponsors: The Hong Kong Polytechnic University
Recruiting

Phase 1 Study of 68Ga-R8760

Posted: August 21st, 2023, 11:00pm UTC

Conditions: Adrenocortical Carcinoma
Interventions: Drug: 68Ga-R8760 injection at pre-defined dose levels; Drug: 68Ga-R8760 injection
Sponsors: Radionetics Oncology
Active, not recruiting

Evaluation of the Efficacy of Addition of Progesterone to Standard Chemotherapy in Adrenocortical Carcinoma (ACC)

Posted: June 22nd, 2023, 11:00pm UTC

Conditions: Adrenocortical Carcinoma
Interventions: Drug: Etoposide, doxorubicin, cisplatin and Mitotane plus Megestrol Acetate 160 MG; Drug: Etoposide, doxorubicin, cisplatin and Mitotane plus Placebo
Sponsors: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Recruiting

Intercostal Cryoanalgesia for Acute Pain After VATS Lung Resection

Posted: June 9th, 2023, 11:00pm UTC

Conditions: Thoracic Surgery; Video-Assisted; Cryotherapy Effect; Paravertebral Block
Interventions: Procedure: Cryoanalgesia AND single-injection paravertebral block; Procedure: Single-injection paravertebral block
Sponsors: Centre hospitalier de l'UniversitÃ© de MontrÃ©al (CHUM)
Recruiting

Intercostal Cryoanalgesia for Chronic Pain After VATS Lung Resection

Posted: June 1st, 2023, 11:00pm UTC

Conditions: Cryotherapy Effect; Chronic Pain; Lung Cancer; Surgery
Interventions: Procedure: Cryoanalgesia AND single-injection paravertebral block; Procedure: Single-injection paravertebral block
Sponsors: Centre hospitalier de l'UniversitÃ© de MontrÃ©al (CHUM)
Recruiting

18F-FDGal PET/CT and PET/MRI in Patients With Hepatocellular Carcinoma

Posted: May 23rd, 2023, 11:00pm UTC

Conditions: Hepatocellular Carcinoma
Interventions: Diagnostic Test: 18F-FDGal PET/CT or PET/MRI
Sponsors: University of Aarhus
Recruiting

Intratumoral Gemcitabine, Paclitaxel, Carboplatine and Intravenous Nivolumab for Locally Recurrence of Head and Neck Cancers

Posted: April 28th, 2023, 11:00pm UTC

Conditions: Squamous Cell Carcinoma of the Head and Neck; Paclitaxel; Carboplatin; Nivolumab
Interventions: Drug: GCP intratumoral catheter
Sponsors: Centre Hospitalier Universitaire, Amiens
Not yet recruiting

Ramadan Fasting in Secondary Adrenal Insufficiency Patients

Posted: April 25th, 2023, 11:00pm UTC

Conditions: Secondary Adrenal Insufficiency; Fasting, Intermittent
Interventions: Behavioral: education and drug adjustement
Sponsors: Hopital La Rabta
Active, not recruiting

Colonoscopic Sucralfate Spray in Prevention of Delayed Polypectomy Bleeding

Posted: April 18th, 2023, 11:00pm UTC

Conditions: Bleeding
Interventions: Drug: Sucralfate
Sponsors: National Cheng-Kung University Hospital
Recruiting

A Study to Evaluate the Safety and PK of CRN04894 for the Treatment of Cushing's Syndrome

Posted: April 7th, 2023, 11:00pm UTC

Conditions: Cushing Syndrome; Cushing Disease; Ectopic ACTH Syndrome
Interventions: Drug: CRN04894
Sponsors: Crinetics Pharmaceuticals Inc.
Recruiting

Permalink for 'Single vs. Multiple Fraction Trial of Stereotactic Ablative Radiotherapy for Comprehensive Treatment of Oligometastases/Progression'

Single vs. Multiple Fraction Trial of Stereotactic Ablative Radiotherapy for Comprehensive Treatment of Oligometastases/Progression

Posted: March 24th, 2023, 11:00pm UTC

Conditions: Oligometastatic Disease; Oligoprogression; Toxicity Due to Radiotherapy; Quality of Life
Interventions: Radiation: Single fraction SABR; Radiation: Multiple fraction SABR; Other: QoL reporting alone; Other: QoL reporting, symptom screen and healthcare provider intervention
Sponsors: British Columbia Cancer Agency; London Regional Cancer Program, Canada; Tom Baker Cancer Centre; Princess Margaret Hospital, Canada
Not yet recruiting

Positioning of Molecular Markers in Clinical Routine for the Management of Patients With Adrenal Cancers/Tumors (COMETE-CARE)

Posted: March 6th, 2023, 1:00am UTC

Conditions: Cancer; Adrenal
Interventions: Other: Blood sample; Other: Urine sample; Other: Tumor sample
Sponsors: Assistance Publique - HÃ´pitaux de Paris; National Cancer Institute, France
Recruiting

The Effect and Safety of Omitting Preoperative Alpha-adrenergic Blockade for Normotensive Pheochromocytoma

Posted: January 27th, 2023, 1:00am UTC

Conditions: Pheochromocytoma; Paraganglioma; Adrenalectomy; Status; Adrenergics Causing Adverse Effects in Therapeutic Use
Interventions: Drug: Phenoxybenzamine
Sponsors: Seoul National University Hospital
Recruiting

Baby Detect : Genomic Newborn Screening

Posted: January 18th, 2023, 1:00am UTC

Conditions: Congenital Adrenal Hyperplasia; Familial Hyperinsulinemic Hypoglycemia 1; Phosphoglucomutase 1 Deficiency; Maturity Onset Diabetes of the Young; Cystic Fibrosis; Hypophosphatasia, Infantile; Congenital Hypothyroidism; Deficit in Anterior Pituitary Function and Variable Immunodeficiency; Pituitary Hormone Deficiency, Combined; Diamond Blackfan Anemia; Wiskott-Aldrich Syndrome; Fanconi Anemia; Hemophilia A; Hemophilia B; Glucose 6 Phosphate Dehydrogenase Deficiency; Alpha-Thalassemia; Sickle Cell Disease; Shwachman-Diamond Syndrome; Alpha 1-Antitrypsin Deficiency; Inflammatory Bowel Disease 25, Autosomal Recessive; Wilson Disease; Progressive Familial Intrahepatic Cholestasis; Crigler-Najjar Syndrome; Familial Chylomicronemia; Lysosomal Acid Lipase Deficiency; Familial Hemophagocytic Lymphocytosis; Griscelli Syndrome; Chediak-Higashi Syndrome; Severe Congenital Neutropenia; Severe Combined Immune Deficiency; Chronic Granulomatous Disease; Menkes Disease; Adrenoleukodystrophy; Smith-Lemli-Opitz Syndrome; Ataxia With Vitamin E Deficiency; Thiamine Metabolism Dysfunction Syndrome 5 (Episodic Encephalopathy Type); Thiamine Metabolism Dysfunction Syndrome 4 (Bilateral Striatal Degeneration and Progressive Polyneuropathy Type); Thiamine-Responsive Megaloblastic Anemia; Thiamine Metabolism Dysfunction Syndrome 2; Deficiency of GOT2; Cerebral Folate Transport Deficiency; Segawa Syndrome, Autosomal Recessive; Congenital Myasthenic Syndrome; Metachromatic Leukodystrophy; Sepiapterin Reductase Deficiency; Dopamine Beta Hydroxylase Deficiency; Glut1 Deficiency Syndrome; Late-Infantile Neuronal Ceroid Lipofuscinosis; Aromatic L-amino Acid Decarboxylase Deficiency; Charcot-Marie-Tooth Disease, Type 6C; Hereditary Hyperekplexia; Brain Dopamine-Serotonin Vesicular Transport Disease; Very Long Chain Hydroxy Acyl Dehydrogenase Deficiency; Tyrosinemia, Type I; Disaccharide Intolerance I; Beta Ketothiolase Deficiency; Phosphoglycerate Dehydrogenase Deficiency; Succinyl-Coa:3-Ketoacid Coa-Transferase Deficiency; Pyridoxine-5'-Phosphate Oxidase Deficiency; Pyridoxine-Dependent Epilepsy; Propionic Acidemia; Pompe Disease; Phenylalanine Hydroxylase Deficiency; Ornithine Transcarbamylase Deficiency; N Acetyl Glutamate Synthetase Deficiency; Riboflavin Deficiency; Maple Syrup Urine Disease; Medium Chain Acyl CoA Dehydrogenase Deficiency; Malonic Acidemia; Long-chain 3-hydroxyacyl-CoA Dehydrogenase Deficiency; Isovaleric Acidemia; Phosphoserine Aminotransferase Deficiency; Phosphoserine Phosphatase Deficiency; Hyperornithinemia-Hyperammonemia-Homocitrullinuria; S-Adenosylhomocysteine Hydrolase Deficiency; Mucopolysaccharidosis VII; Mucopolysaccharidosis VI; Mucopolysaccharidosis IV A; Mucopolysaccharidosis II; Mucopolysaccharidosis I; Transcobalamin Deficiency; Isolated Methylmalonic Acidemia; Cobalamin Deficiency; Homocystinuria; Holocarboxylase Synthetase Deficiency; Fanconi Bickel Syndrome; Glycogen Storage Disease; Glycine Encephalopathy; Glutaric Acidemia I; Glucose Galactose Malabsorption; Gaucher Disease, Type 1; Galactosemias; Fructosemia; Fructose-1,6-Diphosphatase Deficiency; Carbamoyl Phosphate Synthase 1 Deficiency; Citrullinemia Type II; Citrullinemia 1; Creatine Deficiency Syndrome; Systemic Primary Carnitine Deficiency; Carnitine Palmitoyltransferase Deficiency 2; Carnitine Palmitoyltransferase Deficiency 1; Carnitine Acylcarnitine Translocase Deficiency; Riboflavin Transporter Deficiency; Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency; Andersen Tawil Syndrome; Timothy Syndrome; Jervell-Lange Nielsen Syndrome; Catecholaminergic Polymorphic Ventricular Tachycardia; Familial Hypertrophic Cardiomyopathy Type 4; Pseudohypoaldosteronism, Type II; Pseudohypoaldosteronism Type 1; Primary Hyperoxaluria; X Linked Hypophosphatemia; Hereditary Nephrogenic Diabetes Insipidus; Cystinosis; Congenital Nephrotic Syndrome, Finnish Type; Alport Syndrome; Hereditary Retinoblastoma; Biotinidase Deficiency; Aciduria, Argininosuccinic; Argininemia; Acyl-CoA Dehydrogenase Family, Member 9, Deficiency of; 3-Hydroxy 3-Methyl Glutaric Aciduria; 3-Hydroxy-3-Methylglutaryl-CoA Synthase 2 Deficiency
Sponsors: Centre Hospitalier Universitaire de Liege; Centre Hospitalier RÃ©gional de la Citadelle; University of Liege; Sanofi; Orchard Therapeutics; Takeda; Zentech-Lacar Company; Leon Fredericq Foundation
Recruiting

Permalink for 'Propranolol in Combination With Pembrolizumab and Standard Chemotherapy for the Treatment of Unresectable Locally Advanced or Metastatic Esophageal or Gastroesophageal Junction Adenocarcinoma'

Propranolol in Combination With Pembrolizumab and Standard Chemotherapy for the Treatment of Unresectable Locally Advanced or Metastatic Esophageal or Gastroesophageal Junction Adenocarcinoma

Posted: December 15th, 2022, 1:00am UTC

Conditions: Clinical Stage II Esophageal Adenocarcinoma AJCC v8; Clinical Stage III Esophageal Adenocarcinoma AJCC v8; Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IV Esophageal Adenocarcinoma AJCC v8; Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8; Locally Advanced Esophageal Adenocarcinoma; Locally Advanced Gastroesophageal Junction Adenocarcinoma; Metastatic Esophageal Adenocarcinoma; Metastatic Gastroesophageal Junction Adenocarcinoma; Unresectable Esophageal Adenocarcinoma; Unresectable Gastroesophageal Junction Adenocarcinoma
Interventions: Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Fluorouracil; Drug: Leucovorin; Drug: Oxaliplatin; Biological: Pembrolizumab; Drug: Propranolol Hydrochloride; Other: Questionnaire Administration
Sponsors: Roswell Park Cancer Institute; United States Department of Defense
Recruiting

Efficacy and Safety of HYbrid Argon Plasma Coagulation Technique in Patients With Barrett's Esophagus-Related Dysplasia

Posted: December 9th, 2022, 1:00am UTC

Conditions: Barrett's Esophagus
Interventions: Device: Hybrid Argon Plasma Coagulation System
Sponsors: Istituto Clinico Humanitas
Recruiting

The Effects of oXiris in Cardiogenic Shock Requiring VA-ECMO

Posted: December 8th, 2022, 1:00am UTC

Conditions: Cardiogenic Shock
Interventions: Device: oXiris membrane; Diagnostic Test: Blood tests
Sponsors: Samsung Medical Center
Completed

A Multicentre Study on Features of the Gut Microbiota of Patients With Critical Chronic Diseases in China

Posted: December 6th, 2022, 1:00am UTC

Conditions: Essential Hypertension; Liver Cancer; Nasopharyngeal Cancer; Pancreatic Cancer; Lung Cancer; Chronic Kidney Diseases; Acute Coronary Syndrome; Epilepsy; Gastric Cancer; Primary Aldosteronism; Subclinical hypothyroÃ¯dism
Interventions: Other: no intervention
Sponsors: Zhujiang Hospital; National Natural Science Foundation of China
Recruiting

Permalink for 'A Phase II Study to Evaluate the Efficacy and Safety of Pembrolizumab in Combination With Mitotane in Patients With Advanced Adrenocortical Carcinoma'

A Phase II Study to Evaluate the Efficacy and Safety of Pembrolizumab in Combination With Mitotane in Patients With Advanced Adrenocortical Carcinoma

Posted: December 2nd, 2022, 1:00am UTC

Conditions: Adrenocortical Carcinoma
Interventions: Drug: Mitotane; Drug: Pembrolizumab
Sponsors: M.D. Anderson Cancer Center
Completed

Comparison of Three Different Puncture Techniques in EBUS-TBNA

Posted: November 28th, 2022, 1:00am UTC

Conditions: Lung Cancer; Sarcoidosis; Tuberculosis
Interventions: Procedure: Endobronchial ultrasound-guided transbronchial needle Slow-pull capillary sampling; Procedure: Endobronchial ultrasound-guided transbronchial needle aspiration; Procedure: Endobronchial ultrasound-guided transbronchial needle capillary sampling
Sponsors: Beijing Friendship Hospital
Recruiting

Effects of Acute and Chronic Exercise on Myeloid-Derived Suppressor Cells in Melanoma Patients

Posted: November 14th, 2022, 1:00am UTC

Conditions: Melanoma
Interventions: Other: AEP Group Walking Sessions; Other: CEP Group Walking Sessions
Sponsors: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Completed

Pulsed Radiofrequency of S2-4 Versus Ganglion Impar Neurolysis for Severe Perianal and Perineal Pain in Cancer Patients

Posted: October 24th, 2022, 11:00pm UTC

Conditions: Analgesia
Interventions: Procedure: Ganglion Impar Neurolysis; Procedure: Bilateral S2, S3 and S4 Pulsed radiofrequency
Sponsors: National Cancer Institute, Egypt
Completed

Molecular and Clinical Risk-Directed Therapy for Infants and Young Children With Newly Diagnosed Medulloblastoma

Posted: September 10th, 2022, 11:00pm UTC

Conditions: Medulloblastoma
Interventions: Procedure: Surgical resection; Procedure: Ommaya/VPS; Drug: Methotrexate; Drug: Cisplatin; Drug: Vincristine; Drug: Cyclophosphamide; Drug: Carboplatin; Drug: Topotecan; Drug: Etoposide; Drug: Pegfilgrastim; Drug: Filgrastim; Radiation: Irradiation; Other: Educational and Media Intervention; Other: SOC, Educational and Media Intervention
Sponsors: St. Jude Children's Research Hospital
Recruiting

Translational Research Center in Lung Cancer Disparities (TRACER) Project 2

Posted: August 5th, 2022, 11:00pm UTC

Conditions: Smoking; Smoking Behaviors; Smoking Cessation; Stress Reaction
Sponsors: Virginia Commonwealth University; City of Hope Medical Center; Medical University of South Carolina; National Cancer Institute (NCI)
Recruiting

Nivolumab and DAY101 for Treatment of Craniopharyngioma in Children and Young Adults

Posted: July 19th, 2022, 11:00pm UTC

Conditions: Craniopharyngioma, Child; Craniopharyngioma; Recurrent Craniopharyngioma
Interventions: Drug: Nivolumab; Drug: Tovorafenib
Sponsors: Sabine Mueller, MD, PhD; Bristol-Myers Squibb; Day One Biopharmaceuticals, Inc.
Recruiting

Postmortem Evaluation of Adrenal and Other Endocrine Tumors in Patients With Sudden Death

Posted: July 7th, 2022, 11:00pm UTC

Conditions: Primary Aldosteronism; Adrenal Cushing Syndrome; Pheochromocytoma; Endocrine Neoplasia
Interventions: Diagnostic Test: Adrenal aldosterone synthase (CYP11B2) staining; Diagnostic Test: Adrenal cortisol synthase (CYP11B1) staining; Diagnostic Test: Histopathological analysis
Sponsors: Helsinki University Central Hospital; Finnish Institute for Health and Welfare; University of Helsinki; Tampere University Hospital; Tampere University
Active, not recruiting

SPI-62 as a Treatment for Hypercortisolism Related to a Benign Adrenal Tumor

Posted: June 29th, 2022, 11:00pm UTC

Conditions: Autonomous Cortisol Secretion (ACS); ACTH-Independent Cushing Syndrome; ACTH-Independent Adrenal Cushing Syndrome, Somatic
Interventions: Drug: SPI-62 dose
Sponsors: Sparrow Pharmaceuticals
Active, not recruiting

Prebiotic and Probiotic Modulation of the Gut Microbiota-gut-brain Axis During Acute Stress

Posted: May 26th, 2022, 11:00pm UTC

Conditions: Stress Physiology
Interventions: Dietary Supplement: Probiotic; Dietary Supplement: Prebiotic; Other: Placebo
Sponsors: United States Army Research Institute of Environmental Medicine; United States Army Combat Capabilities Development Command Soldier Center; United States Air Force Research Laboratory
Recruiting

Non-interventional Study on Osilodrostat in Patients With Endogenous Cushing's Syndrome

Posted: May 19th, 2022, 11:00pm UTC

Conditions: Endogenous Cushing's Syndrome
Interventions: Drug: Osilodrostat
Sponsors: RECORDATI GROUP
Active, not recruiting

Endoscopic Ultrasound-guided Radiofrequency Ablation in Primary Aldosteronism

Posted: May 10th, 2022, 11:00pm UTC

Conditions: Primary Aldosteronism; Aldosterone-Producing Adenoma; Hypercortisolism
Interventions: Procedure: EUS-RFA of left adrenal tumour in PA with AVS-verified left lateralisation; Procedure: EUS-RFA of left adrenal tumour in PA, "debulking group"; Procedure: EUS-RFA of left adrenal tumour in MACS with AVS-verified left lateralisation; Procedure: EUS-RFA of left adrenal tumour in MACS with bilateral overproduction, "debulking group
Sponsors: Haukeland University Hospital
Recruiting

Survivorship Plan HEalth REcord (SPHERE) Implementation Trial

Posted: April 26th, 2022, 11:00pm UTC

Conditions: Cancer
Interventions: Behavioral: Survivorship Care Plan-Personal Health Record (SCP-PHR)
Sponsors: Indiana University; National Cancer Institute (NCI)
Recruiting

Tranexamic Acid During Colonic Endoscopic Resection Procedures

Posted: April 26th, 2022, 11:00pm UTC

Conditions: Colon Neoplasm
Interventions: Drug: Tranexamic acid; Drug: Standard
Sponsors: Assaf-Harofeh Medical Center
Recruiting

SPI-62 as a Treatment for Adrenocorticotropic Hormone-dependent Cushing's Syndrome

Posted: April 1st, 2022, 11:00pm UTC

Conditions: Cushing's Syndrome I; Cushing Disease Due to Increased ACTH Secretion; Cortisol Excess; Cortisol; Hypersecretion; Cortisol Overproduction; Ectopic ACTH Secretion
Interventions: Drug: SPI-62; Drug: Placebo
Sponsors: Sparrow Pharmaceuticals
Active, not recruiting

Bacteriostatic Saline as a Local Anesthetic in Minor Eyelid Procedures

Posted: March 24th, 2022, 11:00pm UTC

Conditions: Eyelid Tumor; Eyelid Bump; Eyelid Deformity; Eyelid Abscess; Eyelid Boil; Eyelid Papilloma; Anesthesia, Local; Ophthalmology
Interventions: Drug: 0.9% Bacteriostatic Local Anesthetic Injection; Drug: 1% Lidocaine with 1:100,000 epinephrine Local Anesthetic Injection; Procedure: Eyelid Lesion Removal
Sponsors: University of California, San Francisco
Completed

Tissue Procurement and Natural History Study of Neuroendocrine Neoplasms (NENs) Including Adrenocortical Carcinoma (ACC)

Posted: February 14th, 2022, 1:00am UTC

Conditions: Neuroendocrine Tumors; Carcinoma, Neuroendocrine
Sponsors: National Cancer Institute (NCI)
Recruiting

Dual-labeled anti-GD2 targeted probe for intraoperative molecular imaging of neuroblastoma

Fetched: October 16th, 2024, 2:00am UTC by Lauren Taylor Rosenblum

J Transl Med. 2024 Oct 15;22(1):940. doi: 10.1186/s12967-024-05728-0.

ABSTRACT

BACKGROUND: Surgical resection is integral for the treatment of neuroblastoma, the most common extracranial solid malignancy in children. Safely locating and resecting primary tumor and remote deposits of disease remains a significant challenge, resulting in high rates of complications and incomplete surgery, worsening outcomes. Intraoperative molecular imaging (IMI) uses targeted radioactive or fluorescent tracers to identify and visualize tumors intraoperatively. GD2 was selected as an IMI target, as it is highly overexpressed in neuroblastoma and minimally expressed in normal tissue.

METHODS: GD2 expression in neuroblastoma cell lines was measured by flow cytometry. DTPA and IRDye^Â® 800CW were conjugated to anti-GD2 antibody to generate DTPA-Î±GD2-IR800. Binding affinity (Kd) of the antibody and the non-radiolabeled tracer were then measured by ELISA assay. Human neuroblastoma SK-N-BE(2) cells were surgically injected into the left adrenal gland of 3.5-5-week-old nude mice and the orthotopic xenograft tumors grew for 5 weeks. ¹¹¹In-Î±GD2-IR800 or isotype control tracer was administered via tail vein injection. After 4 and 6 days, mice were euthanized and gamma and fluorescence biodistributions were measured using a gamma counter and ImageJ analysis of acquired SPY-PHI fluorescence images of resected organs (including tumor, contralateral adrenal, kidneys, liver, muscle, blood, and others). Organ uptake was compared by one-way ANOVA (with a separate analysis for each tracer/day combination), and if significant, Sidak's multiple comparison test was used to compare the uptake of each organ to the tumor. Handheld tools were also used to detect and visualize tumor in situ, and to assess for residual disease following non-guided resection.

RESULTS: ¹¹¹In-Î±GD2-IR800 was successfully synthesized with 0.75-2.0 DTPA and 2-3 IRDye^Â® 800CW per antibody and retained adequate antigen-binding (Kd = 2.39 nM for aGD2 vs. 21.31 nM for DTPA-aGD2-IR800). The anti-GD2 tracer demonstrated antigen-specific uptake in mice with human neuroblastoma xenografts (gamma biodistribution tumor-to-blood ratios of 3.87 and 3.88 on days 4 and 6 with anti-GD2 tracer), while isotype control tracer did not accumulate (0.414 and 0.514 on days 4 and 6). Probe accumulation in xenografts was detected and visualized using widely available operative tools (Neoprobe^Â® and SPY-PHI camera) and facilitated detection ofputative residual disease in the resection cavity following unguided resection.

CONCLUSIONS: We have developed a dual-labeled anti-GD2 antibody-based tracer that incorporates In-111 and IRDye^Â® 800CW for radio- and fluorescence-guided surgery, respectively. The tracer adequately binds to GD2, specifically accumulates in GD2-expressing xenograft tumors, and enables tumor visualization with a hand-held NIR camera. These results encourage the development of ¹¹¹In-Î±GD2-IR800 for future use in children with neuroblastoma, with the goal of improving patient safety, completeness of resection, and overall patient outcomes.

PMID:39407274 | DOI:10.1186/s12967-024-05728-0

AGO2 protein: a key enzyme in the miRNA pathway as a novel biomarker in adrenocortical carcinoma

Fetched: October 16th, 2024, 2:00am UTC by Anila Hashmi

Endocr Relat Cancer. 2024 Oct 1:ERC-24-0061. doi: 10.1530/ERC-24-0061. Online ahead of print.

ABSTRACT

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy characterised by diagnostic challenges, high recurrence rates, and poor prognosis. This study explored the role microRNA (miRNA) processing genes in ACC, and their potential role as diagnostic and prognostic biomarkers. We analysed the mRNA expression levels of miRNA machinery components (DROSHA, DGCR8, XPO5, RAN, DICER, TARBP2 and AGO2) utilising mRNA-Seq data from The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) projects. Additionally, protein levels were quantified in tissue samples from the Kolling Institute of Medical Research's tumour bank. Our results demonstrated that among all miRNA processing components, AGO2 exhibited significant overexpression in ACC compared to the normal adrenal cortex (NAC) and benign adrenal adenoma (AA) (p < 0.001). Kaplan-Meier survival analysis indicated that higher AGO2 expression correlated with significantly worse overall survival in ACC patients (HR 7.07, p < 0.001). Among 32 cancer types in TCGA, the prognostic significance of AGO2 was most prominent in ACC. This study is the first to report AGO2's potential as a diagnostic and prognostic biomarker in ACC, emphasising its significance in ACC pathogenesis and potential application as a non-invasive liquid biopsy biomarker.

PMID:39404265 | DOI:10.1530/ERC-24-0061

Permalink for 'A pathological complete response and adrenal insufficiency in a patient with advanced renal pelvic cancer treated with pembrolizumab'

A pathological complete response and adrenal insufficiency in a patient with advanced renal pelvic cancer treated with pembrolizumab

Fetched: October 16th, 2024, 2:00am UTC by Kotaro Suzuki

Int Cancer Conf J. 2024 Jul 2;13(4):391-394. doi: 10.1007/s13691-024-00695-1. eCollection 2024 Oct.

ABSTRACT

Metastatic upper tract urothelial carcinoma (mUTUC) often has poor prognosis. While systemic therapy is the standard care for mUTUC, lymph node dissection (LND) combined with radical nephroureterectomy (RNU) can be considered for patients with only clinical locoregional LN, resulting in a surgical cure. However, since pembrolizumab, an anti-PD-1 monoclonal antibody, was approved for mUTUC patients, prognosis of mUTUC has been improved and some patients with immune-related adverse events have experienced a clinical complete response and a long-lasting therapeutic response without surgery. Thus, clarifying the optimal patient selection and timing for RNU + LND is warranted to avoid unnecessary surgery. We herein report the first unique case with a clinical N + UTUC patient who underwent RNU plus LND and showed a pathological complete response after discontinuation of pembrolizumab due to adrenal insufficiency. We feel that our case may affect the treatment strategy for N + UTUC in the era of ICIs.

PMID:39398924 | PMC:PMC11464843 | DOI:10.1007/s13691-024-00695-1

Cushing's Storm: A Case of Paraneoplastic Cushing's Syndrome-Induced Seizures Treated With Continuous Etomidate Infusion

Fetched: October 16th, 2024, 2:00am UTC by Christopher B Marsalisi

Cureus. 2024 Sep 11;16(9):e69193. doi: 10.7759/cureus.69193. eCollection 2024 Sep.

ABSTRACT

A 67-year-old female presented with abdominal pain, nausea, vomiting, and unintentional weight loss. Further work-up revealed elevated serum cortisol, hypokalemia, and metabolic alkalosis in the setting of paraneoplastic Cushing's syndrome secondary to small lung cancer. The patient then developed refractory convulsive epileptic seizure despite being on multiple anti-epileptic medications. Here, we present a unique case where continuous etomidate infusion was used to lower serum cortisol, as adrenal insufficiency is associated with etomidate use. This case emphasizes how drug side effects can be used to achieve a desired treatment outcome.

PMID:39398809 | PMC:PMC11469216 | DOI:10.7759/cureus.69193

Privacy-friendly evaluation of patient data with secure multiparty computation in a European pilot study

Fetched: October 16th, 2024, 2:00am UTC by Hendrik Ballhausen

NPJ Digit Med. 2024 Oct 14;7(1):280. doi: 10.1038/s41746-024-01293-4.

ABSTRACT

In multicentric studies, data sharing between institutions might negatively impact patient privacy or data security. An alternative is federated analysis by secure multiparty computation. This pilot study demonstrates an architecture and implementation addressing both technical challenges and legal difficulties in the particularly demanding setting of clinical research on cancer patients within the strict European regulation on patient privacy and data protection: 24 patients from LMU University Hospital in Munich, Germany, and 24 patients from Policlinico Universitario Fondazione Agostino Gemelli, Rome, Italy, were treated for adrenal gland metastasis with typically 40 Gy in 3 or 5 fractions of online-adaptive radiotherapy guided by real-time MR. High local control (21% complete remission, 27% partial remission, 40% stable disease) and low toxicity (73% reporting no toxicity) were observed. Median overall survival was 19 months. Federated analysis was found to improve clinical science through privacy-friendly evaluation of patient data in the European health data space.

PMID:39397162 | PMC:PMC11471812 | DOI:10.1038/s41746-024-01293-4

Sudden Vision Loss in a Patient With Renal Cell Carcinoma: A Potential Indicator of Choroidal Metastasis

Fetched: October 16th, 2024, 2:00am UTC by Nadja KÃ¼hrer

Cureus. 2024 Oct 9;16(10):e71138. doi: 10.7759/cureus.71138. eCollection 2024 Oct.

ABSTRACT

Choroidal metastasis of renal cell cancer (RCC) is an exceptionally rare clinical occurrence. In most cases, sudden vision loss is the first symptom. Here we present the case of a 52-year-old male with papillary RCC first diagnosed in 2018. Three years later, a bronchoscopy with endobronchial ultrasound (EBUS) identified suspicious infracarinal lymph nodes. A biopsy confirmed metastasis from RCC, leading to the initiation of systemic first-line therapy with cabozantinib monotherapy. The patient confirmed an excellent response with complete remission. In 2023, the patient reported for the first time a bilateral decrease in vision. Initial management with corrective lenses was unsuccessful. Further staging indicated metastases in the liver, spleen, and adrenal gland. Consecutively, the therapy was switched to lenvatinib and pembrolizumab. Two months later, an ophthalmologic examination due to persisting vision loss confirmed bilateral choroidal metastases. The systemic therapy was continued, and the patient's vision significantly improved. In 2024, the patient developed immune-associated pneumonitis, initially treated with prednisolone. The pulmonary situation became worse. A CT scan confirmed additional metastases in the lung with lymphangiosis carcinomatosis. Due to a poor performance status, no further systemic therapy has been initiated to date. In conclusion, this case highlights the rarity of choroidal metastases in RCC and the challenges of diagnosis. Ophthalmologic examination in RCC patients experiencing sudden vision loss is essential to detect these specific metastases as soon as possible. Comprehensive documentation and awareness of these rare metastatic manifestations are essential to improving diagnostic accuracy and patient outcomes.

PMID:39391258 | PMC:PMC11465728 | DOI:10.7759/cureus.71138

Immunotherapy Induced Adrenal Insufficiency: An Underdiagnosed Cause of Persistent Hypotension in Cancer

Fetched: October 16th, 2024, 2:00am UTC by Nina H Cheng

J Community Hosp Intern Med Perspect. 2024 Jul 2;14(4):68-70. doi: 10.55729/2000-9666.1375. eCollection 2024.

ABSTRACT

Endocrinopathies following immunotherapy have infrequently been documented in the literature. Adrenal insufficiency is a rare consequence of pembrolizumab immunotherapy, with incidence reported to be between 0.98 and 1.3%. We present the case of a 34-year-old female with triple negative breast cancer on chemotherapy who presented with generalized weakness with tachycardia, tachypnea and hypotension unresponsive to fluids. Despite initial improvement with intravenous hydrocortisone and midodrine, the patient continued to be symptomatically hypotensive following discharge and required re-admission. AM cortisol level was found to be < 0.5 ug/dl and ACTH was <1.5 pg/dL, consistent with secondary adrenal insufficiency. CT abdomen and pelvis was unremarkable for adrenal pathology. Patient had been initiated on pembrolizumab (Keytruda) 4 months prior to presentation as part of neoadjuvant chemotherapy. The patient was provided supportive treatment with discharge on fludrocortisone, prednisone, and midodrine. This case reports an unusual consequence of immune checkpoint inhibitors, in which early diagnostic testing, identification, and management is critical.

PMID:39391114 | PMC:PMC11464065 | DOI:10.55729/2000-9666.1375

Nursing care during management of recurrent pheochromocytoma: A case study

Fetched: October 16th, 2024, 2:00am UTC by Minmin Chen

Nurs Crit Care. 2024 Oct 11. doi: 10.1111/nicc.13165. Online ahead of print.

ABSTRACT

BACKGROUND: Pheochromocytoma can occur in patients with multiple endocrine neoplasia type 2, placing them at increased risk of tumour recurrence after surgical resection. Therefore, management of pheochromocytoma in these patients is a clinical challenge.

AIMS: We aim to present and discuss the nursing management of patient with recurrent pheochromocytoma.

STUDY DESIGN: Case studies. We reviewed and retrieved the necessary information from the medical records.

RESULTS: A 34-year-old female with a history of medullary thyroid carcinoma and pheochromocytoma complicated by cardiomyopathy, who had undergone surgical resections 6 years ago, presented with abdominal pain for 1 day and was diagnosed with recurrent bilateral pheochromocytoma, hypertensive crisis, acute heart failure, and acute renal failure. Eight hours after hospital admission, she experienced sudden cardiac arrest and received cardiopulmonary resuscitations. She was then supported under extracorporeal membrane oxygenation and continuous renal replacement therapy (CRRT). The adrenal tumour was successfully treated with absolute ethanol ablation followed by gelatin sponge particle embolization, a management approach which has not been reported previously. She had a satisfactory recovery.

CONCLUSIONS: A comprehensive nursing management approach, including prone ventilation; safe transportation; close cardiopulmonary monitoring; pre-, intra- and post-procedure care; individualized early rehabilitation; and psychological supports, should be applied to improve the prognoses in patients with similar medical conditions.

RELEVANCE TO CLINICAL PRACTICE: Bilateral adrenal pheochromocytoma can be managed by absolute ethanol ablation followed by gelatin sponge particle embolization. Comprehensive nursing management, including a team effort regarding patient positioning, transportation, close monitoring, early rehabilitation and psychological support, should be provided during the peri-procedure period.

PMID:39390956 | DOI:10.1111/nicc.13165

Permalink for 'Bulky Isolated Adrenal Metastasis as First Presentation of Occult Hepatocellular Carcinoma (HCC) in a Patient with a Synchronous Squamous Carcinoma of the Tongue'

Bulky Isolated Adrenal Metastasis as First Presentation of Occult Hepatocellular Carcinoma (HCC) in a Patient with a Synchronous Squamous Carcinoma of the Tongue

Fetched: October 16th, 2024, 2:00am UTC by Marco Lodin

Endocr Metab Immune Disord Drug Targets. 2024 Oct 10. doi: 10.2174/0118715303337748240910093934. Online ahead of print.

ABSTRACT

BACKGROUND: The diagnostic workup of an adrenal mass should always rule out the possibility of an adrenal metastasis, especially in a patient followed-up for a known primitive cancer. Sometimes, however, the incidental finding of a bulky lesion in a cancer patient can lead to the unexpected diagnosis of metastasis from a second occult cancer. Here, we report the case of a voluminous, isolated left adrenal metastasis from unknown and persistently occult hepatocellular carcinoma (HCC), incidentally found during the follow-up for squamous carcinoma of the tongue.

CASE DESCRIPTION: A 72-year-old HBV/HCV-negative male patient with a history of alcohol abuse was referred to our hospital for gastric bleeding. Some weeks before, the patient was operated on for a locally advanced squamous cell carcinoma of the tongue, which required cervical lymph node neck dissection, temporary tracheostomy, jejunostomy, and plastic reconstruction. Subsequent diagnostic imaging revealed a left adrenal mass sized 9x15 cm with suspicious features. The hormonal workout was negative for pheochromocytoma and a hyperfunctioning adrenal lesion. The patient underwent laparotomic left adrenalectomy. The exploration of the liver was compatible with alcoholic cirrhosis and did not reveal any other palpable lesion. The adrenal mass histologically turned out to be a poorly differentiated G3 HCC. Subsequent radiological exams were unable to identify the primary liver lesion or any other neoplasms. Conversely, Î±-FP levels were initially high but reduced after treatment with sorafenib. After 2 years of follow-up, the patient is alive and well, albeit with evidence of locoregional inter-aortocaval lymphadenopathy. The primary HCC has never been identified, thus suggesting the hypothesis of a diffuse cirrhosis-like HCC.

CONCLUSION: The suspicion of an adrenal metastasis in a patient with primary cancer with a low potential for adrenal metastatic spreading must raise the diagnostic suspect for another synchronous occult cancer beyond that for primary adrenal cancer. HCC can rarely first manifest as a metastatic adrenal lesion.

PMID:39390833 | DOI:10.2174/0118715303337748240910093934

The molecular genetics of adrenal cushing

Fetched: October 16th, 2024, 2:00am UTC by Patricia Vaduva

Hormones (Athens). 2024 Oct 10. doi: 10.1007/s42000-024-00608-0. Online ahead of print.

ABSTRACT

Adrenal Cushing represents 20% of cases of endogenous hypercorticism. Unilateral cortisol-producing adenoma (CPA), a benign tumor, and adrenocortical carcinoma (ACC), a malignant tumor, are more frequent than bilateral adrenal nodular diseases (primary bilateral macronodular adrenal hyperplasia (PBMAH) and primary pigmented nodular adrenal disease (PPNAD)).In cortisol-producing adrenal tumors, the signaling pathways mainly altered are the protein kinase A and Wnt/Î²-catenin pathways. Studying components of these pathways and exploring syndromic and familial cases of these tumors has historically enabled identification of many of the predisposing genes. More recently, pangenomic sequencing revealed alterations in sporadic tumors.In ACC, mainly due to TP53 alterations causing Li-Fraumeni syndrome, germline predisposition is frequent in children, while it is rare in adults. Pathogenic variants in the DNA mismatch repair genes MLH1, MSH2, MSH6, and PMS2, which cause Lynch syndrome or alterations of IGF2 and CDKN1C (11p15 locus) in Beckwith-Wiedemann syndrome, can also cause ACC. Rarely, ACC is described in other hereditary tumor syndromes due to germline pathogenic variants in MEN1 or APC and, in very rare cases, NF1, SDH, PRKAR1A, or BRCA2. Concerning ACC somatic alterations, TP53 and genetic or epigenetic alterations at the 11p15 locus are also frequently described, as well as CTNNB1 and ZNRF3 pathogenic variants.CPAs mainly harbor somatic pathogenic variants in PRKACA and CTNNB1 and, less frequently, PRKAR1A, PRKACB, or GNAS1 pathogenic variants. Isolated PBMAH is due to ARMC5 inactivating pathogenic variants in 20 to 25% of cases and to KDM1A pathogenic variants in food-dependent Cushing. Syndromic PBMAH may be due to germline pathogenic variants in MEN1, APC, or FH, causing type 1 multiple endocrine neoplasia, familial adenomatous polyposis, or hereditary leiomyomatosis-kidney cancer syndrome, respectively. PRKAR1A germline pathogenic variants are the main alteration causing PPNAD (isolated or part of Carney complex).

PMID:39388056 | DOI:10.1007/s42000-024-00608-0

A novel model using leukocytes to differentiating mild autonomous cortisol secretion and non-functioning adrenal adenoma

Fetched: October 16th, 2024, 2:00am UTC by Xin Zhao

Sci Rep. 2024 Oct 9;14(1):23557. doi: 10.1038/s41598-024-74452-y.

ABSTRACT

BACKGROUND: Mild autonomous cortisol secretion (MACS) accounts for a significant proportion of adrenal incidentaloma. Current endocrinological screening tests for MACS are complex, particularly in areas with limited medical resources. This study aimed to develop a diagnostic tool based on leukocyte-related parameters to differentiate between MACS and non-functioning adrenal adenoma (NFA).

METHODS: Inthis retrospective case-control study, propensity score-matching was used to select 567 patients from a cohort of 1108 patients (201 MACS, 907 NFA). External validation cohort included 52MACS and 48 NFA from two hospitals, which did not overlap with the modeling cohort patients. Leukocyte-related parameters were evaluated, and the diagnostic efficacy of each parameter was assessed by calculating Youden's J index (J) and the area under the curve (AUC). The study population was divided into training and testing samples using a 10-fold cross-validation method. Machine learning (ML) and classification and regression tree (CART) model were established.

RESULTS: After propensity score matching, 567 patients were enrolled, including 197 MACS and 370 NFA. With the exception of basophil percentage, all other parameters differed significantly between the two groups. Lymphocyte count, lymphocyte percentage, eosinophils count, eosinophils percentage, and basophil percentage were lower in the MACS group compared to the NFA group. Eosinophils percentage demonstrated the highest AUC (0.650), with a sensitivity of 51.3% and specificity of 73.2%. The ML model, based on multiple parameters,exhibited better performance in diagnosing MACS (sensitivity 76%, specificity 77.4%, and AUC 0.818). A clinically usable CART model achieved an AUC of 0.872, with a sensitivity of 95% and a specificity of 75.7%. In the validation cohort, the prediction accuracy of the ML model and the CART model were 0.784 and 0.798, respectively.

CONCLUSION: TheCART diagnostic model, constructed based on leukocyte-related parameters, could assist clinicians in distinguishing between MACS and NFA.

PMID:39384846 | PMC:PMC11464552 | DOI:10.1038/s41598-024-74452-y

Non-functional muscle-invasive bladder paraganglioma-a case report

Fetched: October 16th, 2024, 2:00am UTC by Joshua S Jue

AME Case Rep. 2024 Sep 5;8:113. doi: 10.21037/acr-24-50. eCollection 2024.

ABSTRACT

BACKGROUND: Extra-adrenal pheochromocytoma (paraganglioma) of the urinary bladder is a rare tumor, accounting for 0.05% of bladder tumors and less than 1% of all paragangliomas. In the genitourinary tract, paragangliomas are most commonly found in the bladder. These tumors have aggressive malignant potential, so complete surgical resection for localized disease is important. Paragangliomas may be non-functional or functional with catecholamine secretions. Although these tumors are rare and difficult to distinguish from urothelial carcinoma (UC), intraoperative manipulation of these tumors may lead to a catecholamine surge and intraoperative complications. Preoperative or early intraoperative recognition of this tumor would facilitate appropriate alpha blockade to minimize morbidity.

CASE DESCRIPTION: Herein we report a rare non-functional paraganglioma arising from the bladder of a 46-year-old male. This case is notable for the location of the mass, requiring a 70-degree cystoscopic lens for complete visualization near the bladder neck, and for the identification of a golden-yellow sessile mass during the resection. Upon visualization of this mass, the operation should be paused for close hemodynamic monitoring and assess for signs of hypertensive crisis prior to continuing without alpha blockade.

CONCLUSIONS: Suspected localized bladder paraganglioma cases should be optimized hemodynamically and managed surgically. Visualization of a sessile bladder mass on gross examination with golden-yellow tumor during the resection should prompt suspicion for a paraganglioma. Biochemical evaluation with serum or urine catecholamines, metanephrines, and normetanephrines should be performed to assess for tumor functionality.

PMID:39380855 | PMC:PMC11459415 | DOI:10.21037/acr-24-50

Adrenocortical neoplasm in a 2-year-old child: Clinical approach and diagnostic imaging

Fetched: October 16th, 2024, 2:00am UTC by Nathalia Sofia Coral-Rivera

Radiol Case Rep. 2024 Sep 25;19(12):6417-6422. doi: 10.1016/j.radcr.2024.09.116. eCollection 2024 Dec.

ABSTRACT

Adrenocortical tumors in children and adolescents are rare and aggressive, accounting for only 0.2% of pediatric cancers, with most cases associated with Li-Fraumeni syndrome. The most common manifestation is virilization due to androgen excess. Imaging techniques are crucial in the diagnosis and management of pediatric adrenocortical carcinoma. CT and MRI are essential for differentiating between benign and malignant lesions and assessing tumor characteristics and extent. Correlating imaging findings with clinical and histopathological data is vital for optimal diagnosis and treatment, underscoring the need for a multidisciplinary approach to managing these rare but aggressive neoplasms. This report presents the case of a previously healthy 2-year-old boy who exhibited virilization symptoms and was diagnosed with adrenocortical carcinoma.

PMID:39380812 | PMC:PMC11460622 | DOI:10.1016/j.radcr.2024.09.116

Deleterious effects of social isolation on neuroendocrine-immune status, and cancer progression in rats

Fetched: October 16th, 2024, 2:00am UTC by Estherina Trachtenberg

Brain Behav Immun. 2024 Oct 6;123:524-539. doi: 10.1016/j.bbi.2024.10.005. Online ahead of print.

ABSTRACT

Accumulating evidence indicates that social isolation (SI) in humans and rodents is associated with increased cancer incidence and mortality, yet mediating mechanisms remain elusive. Here, we examine the neuroendocrine and immunological consequences of SI and its short- and long-term physiological impacts in naÃ¯ve and cancer-bearing rats. Findings indicate that isolated animals experienced a significant decrease in weight compared to controls. Specifically, females showed a marked weight decrease during the first week of isolation. Isolated rats had significantly higher numbers of MADB106 experimental pulmonary metastases. Although mortality rates were higher in isolated tumor-bearing rats, unexpectedly, they exhibited a reduced growth rate of orthotopically implanted MADB106 tumors. Transcriptomic analyses of these excised tumors indicated a major downregulation in the expression of various genes, including those associated with pro-metastatic processes (e.g., EMT). In naÃ¯ve rats (no cancer), levels of IL-6 increased, and total IgG levels decreased under SI conditions. A mixed effect was found for TNFÎ±, which increased in females and decreased in males. In the central nervous system, isolated rats showed altered gene expression in key brain regions associated with stress responses and social behavior. The paraventricular nucleus of the thalamus emerged as a significantly affected region, along with the bed nucleus of the stria terminalis. Changes were observed in the expression of oxytocin, serotonin, and dopamine receptors. Isolated rats also exhibited greater alterations in hypothalamic-pituitary-adrenal (HPA) axis-related regulation and an increase in plasma CORT levels. Our study highlights the profound impact of SI on metastatic processes. Additionally, the potential detrimental effects of SI on thermoregulation were discussed, emphasizing the importance of social thermoregulation in maintaining physiological stability and highlighting the need to avoid single-caging practices in research. We report neuro-immune interactions and changes in brain gene expression, highlighting the need for further research into these underlying processes to improve outcomes in animal models and potential interventions for cancer patients through increased social support.

PMID:39378972 | DOI:10.1016/j.bbi.2024.10.005

Metastatic Axillary Cutaneous Squamous Cell Carcinoma in an African-American Female: A Rare Case

Fetched: October 16th, 2024, 2:00am UTC by Shahriar Sharif

Cureus. 2024 Sep 7;16(9):e68892. doi: 10.7759/cureus.68892. eCollection 2024 Sep.

ABSTRACT

Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer, typically affecting older White males in sun-exposed areas, and metastasis is rare. We present a unique case of a 46-year-old obese African-American woman with a recurrent, deep abscess in her left axilla. It was initially treated with several incision and drainage procedures and antibiotics. Despite multiple interventions, the abscess recurred with severe pain and drainage. Subsequent biopsies revealed a high-grade malignant neoplasm, later confirmed as poorly differentiated cSCC with primary metastases to the lungs and secondary metastases to the adrenal glands and periaortic lymph nodes. Immunohistochemical staining supported the diagnosis. The patient's atypical presentation, including her race, a non-sun-exposed site, and younger age, highlights the need for vigilance in diagnosing cSCC in atypical cases. This case underscores the importance of early consideration of cSCC in differential diagnoses for persistent or recurrent abscesses, which can facilitate timely treatment, potentially preventing extensive metastasis and improving patient outcomes.

PMID:39376866 | PMC:PMC11458060 | DOI:10.7759/cureus.68892

Split-Course Adaptive Radioimmunotherapy for Oligometastatic Non-Small Cell Lung Cancer (SiCARIO): A Case Report

Fetched: October 16th, 2024, 2:00am UTC by Kyra N McComas

Cureus. 2024 Sep 7;16(9):e68868. doi: 10.7759/cureus.68868. eCollection 2024 Sep.

ABSTRACT

Current treatment paradigms for oligometastatic non-small cell lung cancer (NSCLC) utilize systemic chemotherapy alone or in combination with immune checkpoint inhibitors (ICIs). The addition of ICIs in NSCLC has led to significant improvements in survival; however, recurrence remains common. New methods are needed to enhance anti-tumor immune responses and improve patient outcomes. Here, we present the first case of utilization of the Ethos OART platform to deliver multi-site pulsed hypofractionated radiotherapy in a patient with oligometastatic disease on the single arm prospective clinical trial SiCARIO (Split-Course Adaptive Radioimmunotherapy in Oligometastatic NSCLC, NCT05501665). A 67-year-old man with stage IV NSCLC with metastases to bilateral adrenal glands, retroperitoneum, and mesentery was prescribed treatment of 40 Gy in 5 fractions on SiCARIO in combination with SOC chemoimmunotherapy. A multi-target single isocenter approach was utilized to treat nine distinct targets in five total isocenters. Treatment plans were generated using an isotopic approach prioritizing organ at risk (OAR) constraints with the goal of minimum coverage of at least 30 Gy in 5 fractions. CBCT was acquired with each fraction to generate new targets and OAR contours based on anatomic changes with the patient on the treatment table. A comparison of an adapted plan to a base plan was performed online with a selection of superior plans based on target coverage and OAR constraints. The adapted plan was deemed superior for all but 1 fraction of a single isocenter for this patient. The discussion will focus primarily on the bilateral adrenal isocenter, where bulk tumor shrinkage of greater than 80% was observed in this patient with corresponding significant dosimetric benefits. This case demonstrates a potential clinical benefit of OART in multi-metastasis RT. Further data is needed to confirm the safety and efficacy of this approach. Enrollment is ongoing.

PMID:39376864 | PMC:PMC11457801 | DOI:10.7759/cureus.68868

Laparoscopic excision of an incidental vascular tumor

Fetched: October 16th, 2024, 2:00am UTC by Sofia Boligo

J Surg Case Rep. 2024 Oct 5;2024(10):rjae624. doi: 10.1093/jscr/rjae624. eCollection 2024 Oct.

ABSTRACT

Anastomosing hemangioma (AH) is an exceedingly rare benign vascular tumor, often mistaken for malignant neoplasms due to its histological features. First described in 2009, AH has been documented in various sites, including the kidney, liver, and adrenal gland. This report presents a 64-year-old man who, following a bicycle accident, underwent imaging that revealed a nodule suspicious for a paraganglioma in the right para-caval region. Despite the high radiotracer uptake on 68Ga-DOTANOC PET scan, which suggested paraganglioma, the patient remained asymptomatic and laboratory tests ruled out excessive catecholamine secretion. Surgical excision led to a diagnosis of AH, distinguished by its unique anastomosing vascular pattern and histological similarity to angiosarcoma. This case underlines the diagnostic challenges and potential for overtreatment of AH, highlighting the need for heightened awareness and careful histopathological and imaging evaluation to avoid misdiagnosis and ensure appropriate management.

PMID:39376719 | PMC:PMC11456863 | DOI:10.1093/jscr/rjae624

TRPC5 controls the adrenaline-mediated counter regulation of hypoglycemia

Fetched: October 16th, 2024, 2:00am UTC by Jenny BrÃ¶ker-Lai

EMBO J. 2024 Oct 7. doi: 10.1038/s44318-024-00231-0. Online ahead of print.

ABSTRACT

Hypoglycemia triggers autonomic and endocrine counter-regulatory responses to restore glucose homeostasis, a response that is impaired in patients with diabetes and its long-term complication hypoglycemia-associated autonomic failure (HAAF). We show that insulin-evoked hypoglycemia is severely aggravated in mice lacking the cation channel proteins TRPC1, TRPC4, TRPC5, and TRPC6, which cannot be explained by alterations in glucagon or glucocorticoid action. By using various TRPC compound knockout mouse lines, we pinpointed the failure in sympathetic counter-regulation to the lack of the TRPC5 channel subtype in adrenal chromaffin cells, which prevents proper adrenaline rise in blood plasma. Using electrophysiological analyses, we delineate a previously unknown signaling pathway in which stimulation of PAC1 or muscarinic receptors activates TRPC5 channels in a phospholipase-C-dependent manner to induce sustained adrenaline secretion as a crucial step in the sympathetic counter response to insulin-induced hypoglycemia. By comparing metabolites in the plasma, we identified reduced taurine levels after hypoglycemia induction as a commonality in TRPC5-deficient mice and HAAF patients.

PMID:39375537 | DOI:10.1038/s44318-024-00231-0

Gut microbiota causally impacts adrenal function: a two-sample mendelian randomization study

Fetched: October 16th, 2024, 2:00am UTC by Tonghu Liu

Sci Rep. 2024 Oct 7;14(1):23338. doi: 10.1038/s41598-024-73420-w.

ABSTRACT

Some studies have reported that the gut microbiota can influence adrenal-related hormone levels. However, the causal effects of the gut microbiota on adrenal function remain unknown. Therefore, we employed a two-sample Mendelian randomization (MR) study to systematically investigate the impact of gut microbiota on the function of different regions of the adrenal gland. The summary statistics for gut microbiota and adrenal-related hormones used in the two-sample MR analysis were derived from publicly available genome-wide association studies (GWAS). In the MR analysis, inverse variance weighting (IVW) was used as the primary method, with MR-Egger, weighted median, and cML-MA serving as supplementary methods for causal inference. Sensitivity analyses such as the MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis were used to assess pleiotropy and heterogeneity. We identified 27 causal relationships between 23 gut microbiota and adrenal function using the IVW method. Among these, Sellimonas enhanced the function of the adrenal cortex reticularis zone (beta = 0.008, 95% CI: 0.002-0.013, P = 0.0057). The cML-MA method supported our estimate (beta = 0.009, 95% CI: 0.004-0.013, P = 2 Ã— 10^{- 4}). Parasutterella, Sutterella, and Anaerofilum affect the functioning of different regions of the adrenal gland. Notably, pleiotropy was not observed. Our findings revealed that the gut microbiota is causally associated with adrenal function. This enhances our understanding of the gut-microbiota-brain axis and provides assistance in the early diagnosis and treatment of adrenal-related diseases in clinical practice.

PMID:39375408 | PMC:PMC11458771 | DOI:10.1038/s41598-024-73420-w

Permalink for '68Ga-DOTA-FAPI-46 PET/CT Imaging for Restaging in a Patient With Metastatic Pheochromocytoma: Comparison With 68Ga-DOTA-TATE PET/CT'

68Ga-DOTA-FAPI-46 PET/CT Imaging for Restaging in a Patient With Metastatic Pheochromocytoma: Comparison With 68Ga-DOTA-TATE PET/CT

Fetched: October 16th, 2024, 2:00am UTC by Rahime Åžahin

Clin Nucl Med. 2024 Oct 4. doi: 10.1097/RLU.0000000000005481. Online ahead of print.

ABSTRACT

Pheochromocytomas (PHEOs) are neural crest-derived tumors originating from the chromaffin cells of the adrenal medulla and were recognized as one of the subtypes of paragangliomas by the World Health Organization in 2022. 68Ga-labeled somatostatin analog (68Ga-DOTA-NOC, 68Ga-DOTA-TOC, and 68Ga-DOTA-TATE) PET imaging has shown significant performance compared with 123MIBG scintigraphy in the diagnosis of paragangliomas. It is now known that fibroblast activation protein (FAP) is overexpressed by various cancer-associated fibroblasts, including PHEOs. We would like to present the findings of 68Ga-DOTA-FAPI-46 PET/CT and 68Ga-DOTA-TATE PET/CT imaging performed for restaging on a 42-year-old man diagnosed with metastatic PHEO.

PMID:39365092 | DOI:10.1097/RLU.0000000000005481

Permalink for 'Inhaled Corticosteroids Particle Size and Risk of Hospitalization Due to Exacerbations and All-Cause Mortality in Patients with Chronic Obstructive Pulmonary Disease. A Nationwide Cohort Study'

Inhaled Corticosteroids Particle Size and Risk of Hospitalization Due to Exacerbations and All-Cause Mortality in Patients with Chronic Obstructive Pulmonary Disease. A Nationwide Cohort Study

Fetched: October 16th, 2024, 2:00am UTC by Christian Kjer Heerfordt

Int J Chron Obstruct Pulmon Dis. 2024 Sep 29;19:2169-2179. doi: 10.2147/COPD.S453524. eCollection 2024.

ABSTRACT

BACKGROUND: Extra-fine particle inhaled corticosteroids (ICS) improve peripheral airway distribution, but their effect on risk of exacerbations and all-cause mortality in patients with chronic obstructive pulmonary disease (COPD) is unclear.

METHODS: This observational cohort study compares patients with COPD who received extra-fine particle ICS to those who received standard particle size ICS from 2010 to 2017 while followed in outpatient clinics. The primary outcome was the time to a COPD exacerbation that required hospitalization, with all-cause mortality as a secondary outcome. Data were analyzed using an adjusted Cox proportional hazards model and a competing risk analysis. Two predefined subgroup analyses of patients treated with pressurised metered dose inhalers (pMDIs) and patients with a previous exacerbation history, was carried out. Lastly, we created a propensity score matched cohort as a sensitivity analysis.

RESULTS: Of the 40,489 patients included, 38,802 (95.8%) received stand particle size ICS and 1,687 (4.2%) received extra-fine particle ICS. In total 7,058 were hospitalized with a COPD exacerbation, and 4,346 died. No significant protective effect of extra-fine particle ICS against hospitalization due to COPD exacerbations (HR 0.93, 95% CI 0.82-1.05, p=0.23) or all-cause mortality (HR 1.00, 95% CI 0.85-1.17, p=0.99) was found when compared to standard particle size ICS. However, in the subgroup analysis of patients treated with pMDIs, extra-fine particle ICS was associated with reduction in risk of exacerbations (HR 0.72, 95% CI 0.63-0.82, p<0.001) and all-cause mortality (HR 0.72, 95% CI 0.61-0.86, p<0.001).

CONCLUSION: The administration of extra-fine particle ICS was not associated with reduced risk of exacerbations or all-cause mortality in our primary analysis. A subgroup consisting of patients treated with pMDIs suggested potential protective benefits.

PMID:39364225 | PMC:PMC11448463 | DOI:10.2147/COPD.S453524

A rare well-differentiated renal retroperitoneal liposarcoma: a case report

Fetched: October 16th, 2024, 2:00am UTC by M Walid Sukkari

Ann Med Surg (Lond). 2024 Sep 10;86(10):6317-6321. doi: 10.1097/MS9.0000000000002560. eCollection 2024 Oct.

ABSTRACT

INTRODUCTION AND IMPORTANCE: Retroperitoneal liposarcomas (RPLPSs) are rare tumors that arise from mesenchymal cells in the peritoneum cavity. The sites of PRLPSs vary a lot, but renal PRLPSs are extremely rare (there are only 45 cases of Renal retroperitoneal liposarcomas on PubMed). In this case, the authors present a rare renal retroperitoneal liposarcoma case, describe the major concepts, and raise awareness about this rare tumor.

CASE PRESENTATION: A 44-year-old woman presented to the clinic with hirsutism and irregular menstruation; upon physical examination, a large abdominal mass was accidentally identified; the patient had Doppler ultrasound (Doppler US) and MRI, which both showed a mass arising from the right upper pole of the kidney, fine needle aspiration (FNA) confirmed the diagnosis of retroperitoneal liposarcoma, patient underwent surgical removal and her symptoms disappeared.

CLINICAL DISCUSSION: The retroperitoneum is a cavity behind the abdominal wall containing organs like the pancreas and kidneys. Retroperitoneal tumors (RPTs) are rare neoplasms, primarily of mesenchymal origin. Retroperitoneal liposarcomas (RPLPS) are the most common RPT, often asymptomatic until large, and rarely metastasize but frequently recur. Liposarcomas are classified into five subtypes, with well-differentiated liposarcoma being the most common and characterized by high local recurrence. The presence of specific oncologic mutations affects the prognosis and the response to treatment.

CONCLUSION: In rare cases, retroperitoneal liposarcomas can arise from sites near the kidney and compress the adjoining adrenal gland.

PMID:39359852 | PMC:PMC11444529 | DOI:10.1097/MS9.0000000000002560

Permalink for 'Influence of sex and functional status on the value of serum steroid profiling in discriminating adrenocortical carcinoma from adrenocortical adenoma'

Influence of sex and functional status on the value of serum steroid profiling in discriminating adrenocortical carcinoma from adrenocortical adenoma

Fetched: October 16th, 2024, 2:00am UTC by Yan Weng

Front Endocrinol (Lausanne). 2024 Sep 18;15:1435102. doi: 10.3389/fendo.2024.1435102. eCollection 2024.

ABSTRACT

BACKGROUND: It is challenging for clinicians to distinguish adrenocortical carcinoma (ACC) from benign adrenocortical adenomas (ACA) in their early stages. This study explored the value of serum steroid profiling as a complementary biomarker for malignancy diagnosis of ACC other than diameter and explored the influence of sex and functional status.

METHODS: In this retrospective study, a matched cohort of patients diagnosed with either ACC or ACA based on histopathology was meticulously paired in a 1:1 ratio according to sex, age, and functional status. Eight serum steroids including 11-deoxycortisol, 11-deoxycorticosterone, progesterone, androstenedione, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), 17-hydroxyprogesterone, and estradiol, were quantified by liquid chromatography tandem mass spectrometry. We conducted a comparative analysis of the clinical characteristics and serum steroid profiles of patients with ACC and ACA, with further subgroup analysis.

RESULTS: The study included 31 patients with ACC and 31 matched patients with ACA. Patients with ACC exhibited significantly larger tumor diameters, lower body mass index (BMI), and higher levels of 11-deoxycortisol, progesterone, and androstenedione than those with ACA. 11-deoxycortisol was the only valuable index for discriminating ACC from ACA, regardless of functional status and sex. Progesterone, DHEA, and DHEAS levels were higher in the functional ACC group than in the non-functional ACC group. Female ACC patients, especially in postmenopausal female exhibited higher levels of androstenedione than male patients. The area under the curve of tumor diameter, 11-deoxycortisol, and BMI was 0.947 (95% CI 0.889-1.000), with a sensitivity of 96.8% and specificity of 90.3%.

CONCLUSION: Serum steroid profiling serves as a helpful discriminative marker for ACC and ACA, with 11-deoxycortisol being the most valuable marker. For other steroid hormones, consideration of sex differences and functional status is crucial.

PMID:39359414 | PMC:PMC11445004 | DOI:10.3389/fendo.2024.1435102

Near-fatal pheochromocytoma crisis after beta-blocker and tumour haemorrhage

Fetched: October 16th, 2024, 2:00am UTC by Divya Madhavarapu

BMJ Case Rep. 2024 Oct 2;17(10):e260870. doi: 10.1136/bcr-2024-260870.

ABSTRACT

Pheochromocytomas are rare neuroendocrine tumors characterised by the secretion of catecholamines and their metabolites. While some patients may be asymptomatic, they can also present with various symptoms including hypertensive crisis, headaches, palpitations, diaphoresis or other signs of catecholamine toxicity. Adrenal haemorrhage, though rare, is a potentially fatal complication that is often diagnosed during autopsy. In all patients with suspected pheochromocytoma, regardless of whether haemorrhagic conversion has occurred, prompt diagnosis is imperative. Early identification allows for the timely initiation of treatment, preventing potentially life-threatening complications. This case report details the haemorrhagic conversion of an undiagnosed pheochromocytoma in a female patient in her 30s.

PMID:39357917 | DOI:10.1136/bcr-2024-260870

Factors associated with the distribution of brain metastases in lung cancer: a retrospective study

Fetched: October 16th, 2024, 2:00am UTC by Yixin Hu

Clin Exp Metastasis. 2024 Oct 1. doi: 10.1007/s10585-024-10315-0. Online ahead of print.

ABSTRACT

The distribution of brain metastases (BMs) in patients with lung cancer may be associated with the primary tumor-related factors and cerebral small vascular diseases (CSVDs). The aim of this study was to investigate the potential effects of the above factors on the distribution of BMs. A total of 5,788 lesions in 823 patients with BMs from lung cancer were enrolled. The numbers of BMs and CSVDs in 15 brain regions were determined. CSVDs include recent small subcortical infarcts (RSSIs), perivascular spaces, and lacunes of presumed vascular origin (LPVOs). We collected the number of CSVDs, and primary tumor-related factors (including clinical and imaging features) in lung cancer patients with BMs. Univariate and multivariate linear regression were utilized to analyze the potential influence of the above factors on the number of BMs in 15 brain regions. In addition, we performed subgroup analyses of all patients with adenocarcinoma (AD), female patients with AD, male patients with AD, and patients with small cell lung cancer. Univariate linear regression analyses showed that bone metastasis, adrenal metastasis, RSSIs, and LPVOs were associated with the number of BMs in over half of the examined brain regions. Only the independent association of LVPOs persisted in the multivariate linear regression analyses, and similar phenomenon was found in the subgroup analyses. In conclusion, the distribution of BMs in lung cancer patients appears to be associated with the presence of LVPOs, while primary tumor-related factors have less influence.

PMID:39352614 | DOI:10.1007/s10585-024-10315-0

Combined gastroscopic and laparoscopic resection of gastric metastatic adenosquamous carcinoma from lung: A case report

Fetched: October 16th, 2024, 2:00am UTC by Yin Lin

World J Gastrointest Surg. 2024 Sep 27;16(9):3065-3073. doi: 10.4240/wjgs.v16.i9.3065.

ABSTRACT

BACKGROUND: Primary lung cancer is the leading cause of cancer-related death worldwide. Common metastatic sites include the brain, liver, bones, and adrenal glands. However, gastric metastases from lung cancer are rare. This case may be the first report of a combined gastroscopic and laparoscopic resection for gastric metastatic adenosquamous carcinoma (ASC).

CASE SUMMARY: We report a case of gastric metastasis from lung cancer. The patient was a 61-year-old Han Chinese female who first attended our hospital complaining of a persistent cough, leading to the diagnosis of advanced-stage lung adenocarcinoma. After more than four years of chemotherapy, the patient began to experience epigastric pain. Endoscopy was performed, and pathological examination of biopsy specimens confirmed that the gastric lesion was a metastasis from lung cancer. The lesion was successfully resected by combined gastroscopy and laparoscopy. Histopathological examination of the resected gastric specimen revealed ASC.

CONCLUSION: Gastric metastases from lung cancer are rare. Endoscopy, histological and immunohistochemical staining are useful for diagnosing metastatic lesions. Surgical management may provide extended survival in appropriately selected patients.

PMID:39351550 | PMC:PMC11438818 | DOI:10.4240/wjgs.v16.i9.3065

Case Series: ATRX Variants in Four Patients with Metastatic Pheochromocytoma

Fetched: October 16th, 2024, 2:00am UTC by Briana N Cortez

Front Endocrinol (Lausanne). 2024 Sep 16;15:1399847. doi: 10.3389/fendo.2024.1399847. eCollection 2024.

ABSTRACT

Few reports have highlighted the rare presence of somatic ATRX variants in clinically aggressive, metastatic pheochromocytoma/paraganglioma (PCC/PGL); however, none have addressed detailed clinical presentation (including biochemistry and imaging) and management of these patients. Here, we address these clinical features and management based on four PCC patients with somatic ATRX variants from our National Institutes of Health PCC/PGL cohort. A total of 192 patients underwent exome sequencing (germline, somatic, or both), and four males were found to have somatic ATRX variants (with additional somatic VHL and FH oncogenic variants in patients 2 and 4, respectively). Per-lesion and per-patient comparisons were performed among functional imaging scans performed at the NIH. Biochemical phenotype and response to systemic treatment were evaluated. This mini-series supports prior studies showing aggressive/metastatic PCC in patients with somatic ATRX variants, as all developed widespread metastatic disease. All four PCC patients presented with noradrenergic biochemical phenotype, and some with significant elevation in 3-methoxytyramine. ¹⁸F-FDOPA PET/CT was found to be the superior functional imaging modality, with 100% lesion detection rate when compared to that of ⁶⁸Ga-DOTATATE, ¹⁸F-FDG, ¹⁸F-FDA, and ¹²³I-MIBG scans. While patients did not respond to chemotherapy or tyrosine kinase inhibitors, they responded to targeted radiotherapy using high-specific-activity ¹³¹I-MIBG (Azedra^Â®) or ¹⁷⁷Lu-DOTATATE (Lutathera^Â®).

PMID:39351526 | PMC:PMC11439680 | DOI:10.3389/fendo.2024.1399847

Hyper-realistic rendering-assisted laparoscopic adrenalectomy for giant adrenal tumors: a pilot study

Fetched: October 16th, 2024, 2:00am UTC by Jiamo Zhang

World J Urol. 2024 Sep 30;42(1):550. doi: 10.1007/s00345-024-05258-w.

ABSTRACT

PURPOSE: This study aimed to explore the application value of hyperrealistic rendering (HRR) in laparoscopic giant adrenal tumor resection.

METHODS: We retrospectively analyzed 25 patients with giant adrenal tumors from January 2021 to January 2024, with a median age of 56 (40.5, 58.5) years and a tumor median diameter of 7.20 (6.80, 8.50) cm. All patients underwent preoperative medical HRR based on enhanced computed tomography, followed by laparoscopic adrenal tumor resection.

RESULTS: HRR was used to initially determine the nature of the tumor and develop a detailed surgical plan, which was completed in 25 patients preoperatively. All 24 cases of tumors were located in the adrenal gland, 1 case was located in the retroperitoneum, and 13 and 12 cases were on the left and right side, respectively. Preoperative HRR 3D imaging was consistent with the intraoperative situation, and 25 cases had successful surgeries. The median operation time was 165 (120.0, 250.0) min, and median bleeding and blood transfusion volume were 200 (150.0, 450.0) and 200.0 (150.0, 450.0) mL, respectively. There were no collateral injuries to important organs and major vessels and no cases of conversion to open surgery.

CONCLUSION: For large retroperitoneal adrenal tumors, HRR for three-dimensional (3D) reconstruction imaging enables the operator to fully understand the relationship between the tumor and surrounding organs and blood vessels preoperatively, which can reduce intraoperative bleeding and collateral injuries, improve the success rate of laparoscopic resection, and safety of the operation.

PMID:39347828 | DOI:10.1007/s00345-024-05258-w

Experience and andrological follow-up after testicular tissue cryopreservation

Fetched: October 16th, 2024, 2:00am UTC by Romane Levade

Reprod Biomed Online. 2024 Jul 10;49(6):104374. doi: 10.1016/j.rbmo.2024.104374. Online ahead of print.

ABSTRACT

RESEARCH QUESTION: What is the experience and mid- and long-term andrological health follow-up of (pre)pubertal males who have undergone testicular tissue freezing (TTF)?

DESIGN: This single-centre longitudinal retrospective cohort study reports on the mid- and long-term andrological health follow-up of (pre)pubertal males and young adults who underwent TTF for fertility preservation between January 2007 and December 2018. Medical characteristics and questionnaire data collected more than 18 months after TTF were analysed.

RESULTS: Thirty-six patients were revisited during a medical follow-up consultation. During follow-up after TTF, 72.7% of patients could not recollect their counselling consultation prior to TTF but 42.4% of them found information about the TTF process useful and sufficient. Parents' or legal guardians' feedback was more positive about the counselling consultation and the TTF process. After TTF and treatment, the majority of patients (76.9%) who provided a semen sample had non-obstructive azoospermia. Higher serum concentrations of FSH and LH and lower serum concentrations of inhibin B were associated with non-obstructive azoospermia compared with patients with oligozoospermia (P = 0.0182, P = 0.0245 and P = 0.0140 respectively). During cancer treatment, about half of pubertal patients reported sexual dysfunction, decreasing to approximately 20% after treatment. However, two patients had children using sperm donation and one patient had a child through natural pregnancy.

CONCLUSIONS: The involvement of parents or legal guardians is crucial in the decision-making process for fertility preservation in (pre)pubertal boys. Regular follow-up, including the use of questionnaires, is essential to provide guidance for fertility preservation programmes and information on fertility restoration options and to address the psychosocial aspects of fertility preservation.

PMID:39342810 | DOI:10.1016/j.rbmo.2024.104374

Polyamine Pathway Inhibitor DENSPM Suppresses Lipid Metabolism in Pheochromocytoma Cell Line

Fetched: October 16th, 2024, 2:00am UTC by Hans K Ghayee

Int J Mol Sci. 2024 Sep 18;25(18):10029. doi: 10.3390/ijms251810029.

ABSTRACT

Pheochromocytomas (PCCs) are tumors arising from chromaffin cells in the adrenal medulla, and paragangliomas (PGLs) are tumors derived from extra-adrenal sympathetic or parasympathetic paraganglia; these tumors are collectively referred to as PPGL cancer. Treatment for PPGL primarily involves surgical removal of the tumor, and only limited options are available for treatment of the disease once it becomes metastatic. Human carriers of the heterozygous mutations in the succinate dehydrogenase subunit B (SDHB) gene are susceptible to the development of PPGL. A physiologically relevant PCC patient-derived cell line hPheo1 was developed, and SDHB_KD cells carrying a stable short hairpin knockdown of SDHB were derived from it. An untargeted metabolomic approach uncovered an overactive polyamine pathway in the SDHB_KD cells that was subsequently fully validated in a large set of human SDHB-mutant PPGL tumor samples. We previously reported that treatment with the polyamine metabolism inhibitor N¹,N¹¹-diethylnorspermine (DENSPM) drastically inhibited growth of these PCC-derived cells in culture as well as in xenograft mouse models. Here we explored the mechanisms underlying DENSPM action in hPheo1 and SDHB_KD cells. Specifically, by performing an RNAseq analysis, we have identified gene expression changes associated with DENSPM treatment that broadly interfere with all aspects of lipid metabolism, including fatty acid (FA) synthesis, desaturation, and import/uptake. Furthermore, by performing an untargeted lipidomic liquid chromatography-mass spectrometry (LC/MS)-based analysis we uncovered specific groups of lipids that are dramatically reduced as a result of DENSPM treatment. Specifically, the bulk of plasmanyl ether lipid species that have been recently reported as the major determinants of cancer cell fate are notably decreased. In summary, this work suggests an intersection between active polyamine and lipid pathways in PCC cells.

PMID:39337514 | PMC:PMC11432427 | DOI:10.3390/ijms251810029

Synchronous Seminoma of Testis and Renal Cell Carcinoma: A Rare Case Report

Fetched: October 16th, 2024, 2:00am UTC by Stasys Auskalnis

Medicina (Kaunas). 2024 Sep 23;60(9):1553. doi: 10.3390/medicina60091553.

ABSTRACT

Background and Objectives: Seminoma is the most common solid malignant tumour in young men. Clear-cell kidney carcinoma is the most common malignancy of the genitourinary tract. However, the synchronous occurrence of both of these tumours is rare. Case presentation: We present the case of a 36-year-old patient who presented to a medical facility at the end of 2019 with an enlarged right testicle. A unilateral orchofuniculectomy was performed, and a mass measuring 30 cm was removed. During histological examination, testicular seminoma pT2, R0, was diagnosed. An abdominal computed tomography (CT) scan showed a 6.4 cm Ã— 6.8 cm Ã— 6.7 cm tumour in the right kidney and a metastatic-like lesion in the right adrenal gland. A right nephrectomy and an adrenalectomy and paraaortic and paracaval lymphadenectomies were performed. A histological evaluation confirmed the presence of clear-cell renal carcinoma pT2aR0 G2, adrenal hyperplasia, and seminoma metastases in the removed lymph node. Chemotherapy with a Bleomycin, Etoposide, and Cisplatin (BEP) regimen was carried out. Three years after the last cycle of chemotherapy, a follow-up CT scan showed metastases in the left kidney, the right ischium, and the right lung. A well-differentiated clear-cell carcinoma G1 of the left kidney and metastasis of clear-cell carcinoma G2 in the right ischium were confirmed after the biopsy, and no tumour lesions were found in the lung tissue specimen. Treatment with targeted therapy with Sunitinib was started because the risk was favourable according to the Heng criteria. Genetic testing was performed, and the following genes were analysed: VHL, BAP1, CHEK2, FH, MET, MUTYH, APC, and STK11. The testing did not reveal any pathogenic or potentially pathogenic mutations or sequence changes of unknown clinical significance in the genes analysed. Conclusions: According to the authors, the occurrence of synchronous primary tumours is linked to one's genetic predisposition. DNA sequencing of tumour tissue could provide more information on the corresponding aetiopathogenesis.

PMID:39336594 | PMC:PMC11434273 | DOI:10.3390/medicina60091553

Cardiac Paraganglioma in a Young Patient Presents with Angina-like Symptoms: A Case Report and Literature Review

Fetched: October 16th, 2024, 2:00am UTC by Batool Wael Alnahar

Medicina (Kaunas). 2024 Sep 13;60(9):1495. doi: 10.3390/medicina60091495.

ABSTRACT

Paragangliomas are rare extra-adrenal neuroendocrine tumors originating from chromaffin tissue that present a diagnostic and therapeutic challenge due to their diverse clinical manifestations and low incidence. While these tumors often manifest as catecholamine-secreting functional tumors, their clinical presentation can vary, leading to delayed diagnosis and challenging management. This study presents the case of a 22-year-old patient with cardiac paraganglioma who initially presented with angina-like symptoms, highlighting the importance of considering this rare condition in young individuals with nonspecific complaints. Diagnostic imaging, including transthoracic echocardiography, CT angiography, and MRI, played a crucial role in identifying the tumor's location and vascularization. Surgical excision, including pulmonary artery graft and CABG, was the primary management approach, which was accompanied by intraoperative complications that later led to CCU admission, followed by postoperative complications, ultimately leading to the patient's death. This case highlights the significance of early recognition and management of complications following a surgical approach to treat paragangliomas.

PMID:39336536 | PMC:PMC11434372 | DOI:10.3390/medicina60091495

Permalink for 'Epinephrine, Pregabalin, and Crizotinib as Three Medicines with Polish Implications over Three Last Centuries and in View of Three Different Drug Discovery Approaches'

Epinephrine, Pregabalin, and Crizotinib as Three Medicines with Polish Implications over Three Last Centuries and in View of Three Different Drug Discovery Approaches

Fetched: October 16th, 2024, 2:00am UTC by Piotr Kawczak

Biomedicines. 2024 Sep 4;12(9):2021. doi: 10.3390/biomedicines12092021.

ABSTRACT

The discovery of epinephrine (adrenaline) and its subsequent implications in medicine owes significant contributions to Cybulski across different centuries, who, in 1894, was pivotal in identifying the adrenal medulla's role in blood pressure regulation and naming the active substance "nadnerczyna", known today as adrenaline. His work demonstrated the adrenal glands' critical function in the body's regulatory mechanisms beyond the nervous system. Cybulski's groundbreaking research laid foundational knowledge for future endocrinological studies and pharmaceutical advancements. In the late 20th century, Andruszkiewicz collaborated with Silverman at Northwestern University to develop pregabalin, the active ingredient in Lyrica. Their innovative synthesis of gamma-aminobutyric acid derivatives led to a significant advancement in treating epilepsy, neuropathic pain, and fibromyalgia. Andruszkiewicz's expertise in organic chemistry and enzymology was crucial in this collaborative effort, resulting in the successful development and commercialization of Lyrica. Additionally, Mroczkowski's leadership at Pfizer contributed to the development of crizotinib, a notable anaplastic lymphoma kinase and proto-oncogene 1 tyrosine-protein kinase inhibitor used to treat specific types of non-small cell lung cancer. Her work exemplifies the continuing influence of Polish researchers in pioneering drug discovery and advancing therapeutic treatments over the past three centuries. These contributions highlight Poland's significant role in global pharmaceutical innovations and medical research.

PMID:39335535 | PMC:PMC11428485 | DOI:10.3390/biomedicines12092021

Adrenal Insufficiency following Stereotactic Ablative Radiotherapy (SAbR) of Adrenal Gland Metastases

Fetched: October 16th, 2024, 2:00am UTC by Oksana Hamidi

Cancers (Basel). 2024 Sep 12;16(18):3140. doi: 10.3390/cancers16183140.

ABSTRACT

BACKGROUND: Adrenal metastases are often treated with stereotactic ablative radiation (SAbR). We aimed to assess the incidence, timing, and factors associated with the development of primary adrenal insufficiency (PAI) following SAbR.

METHODS: A retrospective cohort study comprised 66 consecutive patients (73% men, median age 61 years) who underwent SAbR for adrenal metastasis.

RESULTS: The series encompassed metastases from renal cell carcinoma (41%), lung tumors (38%), colorectal adenocarcinoma (9%), melanoma (5%), and others (7%). Median follow-up was 17 months from SAbR. Nine (14%) patients developed PAI at a median of 4.3 months (range, 0.7-20.2). The incidence of PAI was 44% in patients with prior adrenalectomy receiving unilateral SAbR, 44% with bilateral SAbR, 2% with unaffected contralateral gland, and 0% with bilateral metastases treated with unilateral SAbR. PAI was associated with prior adrenalectomy (odds ratio [OR] 32) and bilateral SAbR (OR 8.2), but not age, sex, metastasis size, or biological effective dose. Post-SAbR 6-month and 1-year local control rates were 82% and 75%, respectively.

CONCLUSIONS: Patients undergoing SAbR for adrenal metastasis are at high risk of developing PAI. PAI is associated with bilateral SAbR and contralateral adrenalectomy. PAI is unlikely with a remaining unaffected adrenal gland or in the setting of bilateral adrenal metastases with unilateral SAbR.

PMID:39335112 | PMC:PMC11429775 | DOI:10.3390/cancers16183140

Pharmacologically Targeting Ferroptosis and Cuproptosis in Neuroblastoma

Fetched: October 16th, 2024, 2:00am UTC by Ying Liu

Mol Neurobiol. 2024 Sep 27. doi: 10.1007/s12035-024-04501-0. Online ahead of print.

ABSTRACT

Neuroblastoma is a deadly pediatric cancer that originates from the neural crest and frequently develops in the abdomen or adrenal gland. Although multiple approaches, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, are recommended for treating neuroblastoma, the tumor will eventually develop resistance, leading to treatment failure and cancer relapse. Therefore, a firm understanding of the molecular mechanisms underlying therapeutic resistance is vital for the development of new effective therapies. Recent research suggests that cancer-specific modifications to multiple subtypes of nonapoptotic regulated cell death (RCD), such as ferroptosis and cuproptosis, contribute to therapeutic resistance in neuroblastoma. Targeting these specific types of RCD may be viable novel targets for future drug discovery in the treatment of neuroblastoma. In this review, we summarize the core mechanisms by which the inability to properly execute ferroptosis and cuproptosis can enhance the pathogenesis of neuroblastoma. Therefore, we focus on emerging therapeutic compounds that can induce ferroptosis or cuproptosis, delineating their beneficial pharmacodynamic effects in neuroblastoma treatment. Cumulatively, we suggest that the pharmacological stimulation of ferroptosis and ferroptosis may be a novel and therapeutically viable strategy to target neuroblastoma.

PMID:39331355 | DOI:10.1007/s12035-024-04501-0

Could CT Radiomic Analysis of Benign Adrenal Incidentalomas Suggest the Need for Further Endocrinological Evaluation?

Fetched: October 16th, 2024, 2:00am UTC by Alessandro Toniolo

Curr Oncol. 2024 Aug 25;31(9):4917-4926. doi: 10.3390/curroncol31090364.

ABSTRACT

We studied the application of CT texture analysis in adrenal incidentalomas with baseline characteristics of benignity that are highly suggestive of adenoma to find whether there is a correlation between the extracted features and clinical data. Patients with hormonal hypersecretion may require medical attention, even if it does not cause any symptoms. A total of 206 patients affected by adrenal incidentaloma were retrospectively enrolled and divided into non-functioning adrenal adenomas (NFAIs, n = 115) and mild autonomous cortisol secretion (MACS, n = 91). A total of 136 texture parameters were extracted in the unenhanced phase for each volume of interest (VOI). Random Forest was used in the training and validation cohorts to test the accuracy of CT textural features and cortisol-related comorbidities in identifying MACS patients. Twelve parameters were retained in the Random Forest radiomic model, and in the validation cohort, a high specificity (81%) and positive predictive value (74%) were achieved. Notably, if the clinical data were added to the model, the results did not differ. Radiomic analysis of adrenal incidentalomas, in unenhanced CT scans, could screen with a good specificity those patients who will need a further endocrinological evaluation for mild autonomous cortisol secretion, regardless of the clinical information about the cortisol-related comorbidities.

PMID:39329992 | PMC:PMC11431504 | DOI:10.3390/curroncol31090364

On the Origin of Abdominal Venous Leiomyosarcomas: The Role of the Sex-Hormone Drainage Pathways

Fetched: October 16th, 2024, 2:00am UTC by Usman Tarique

World J Oncol. 2024 Oct;15(5):758-768. doi: 10.14740/wjon1884. Epub 2024 Jul 18.

ABSTRACT

BACKGROUND: We hypothesized that abdominal venous leiomyosarcoma (AV-LMS) disproportionately originates in veins of the sex-hormone drainage pathway (SHDP). Our purpose was to classify the anatomical origin of AV-LMS in a large cohort using imaging and explore prognostic implications.

METHODS: A retrospective review of imaging of all patients presenting with abdominal non-uterine LMS at a single tertiary oncology center was performed. Inclusion criteria were a biopsy-proven LMS of non-uterine abdominal/pelvic origin with pretreatment enhanced computed tomography (CT)/magnetic resonance imaging (MRI). Patients with uterine LMS or prior radiation were excluded. LMS site of origin was assigned by one expert radiologist and indeterminate sites were reviewed with a second external expert radiologist. Locations of inferior vena cava (IVC) tumors were subclassified based on a modification of prior literature. SHDP was defined as originating from ovarian/testicular vein, distal left renal vein, adrenal vein or mid-IVC (IIA).

RESULTS: One hundred fifty-five (155) patients were included (92/152 (61%) female) with distant metastases found at presentation in 23/155 (14.8%). Most common organs of origins were veins (84/152, 55.3%), gastrointestinal (24, 15.8%), genital (11, 7.2%) and paratesticular/spermatic cord (11, 7.2%). For venous LMS, the adrenal (both sexes), mid-IVC (IVC IIA, females) and ovarian veins had the highest relative predilection for abdominal non-uterine LMS. Eighty-four (84/152, 55.3%) of tumors were SHDP. On multivariable analysis, both size and SHDP were significant predictors of distant metastases at presentation (P = 0.01), while sex, age, organ system/site and grade were not.

CONCLUSIONS: For both sexes, tumors arising from SHDP constitute the majority of AV-LMS and may impart a significantly lower risk of metastatic disease at presentation. Among veins, the adrenal veins had the highest predilection for LMS.

PMID:39328327 | PMC:PMC11424114 | DOI:10.14740/wjon1884

Case Report: Lung cancer with rare cardiac and other multiple metastases

Fetched: October 16th, 2024, 2:00am UTC by Li Chen

Front Cardiovasc Med. 2024 Sep 12;11:1417906. doi: 10.3389/fcvm.2024.1417906. eCollection 2024.

ABSTRACT

Metastasis to the left atrium is exceptionally uncommon, occurring at a rate of only 3.1%. The clinical manifestations of lung cancer metastasizing to the heart can vary widely. They range from paraneoplastic syndrome, dyspnea, and ST-segment elevation on an electrocardiogram to no clinically significant symptoms. Diverging from typical metastatic patterns observed in lung cancer, this case report presents a detailed description, from the perspective of the microenvironment, of a rare instance where lung cancer metastasized to the mediastinal lymph nodes, adrenal glands, brain, and notably, the left atrium, in a non-smoking female patient.

PMID:39328239 | PMC:PMC11424542 | DOI:10.3389/fcvm.2024.1417906

Recent advancements in new tracers from first-in-human studies

Fetched: October 16th, 2024, 2:00am UTC by Yuji Nakamoto

Ann Nucl Med. 2024 Sep 26. doi: 10.1007/s12149-024-01979-5. Online ahead of print.

ABSTRACT

Recent advancements in the development of positron emission tomography (PET) tracers have significantly enhanced our ability to image neuroinflammatory processes and neurotransmitter systems, which are vital for understanding and treating neurodegenerative and psychiatric disorders. Similarly, innovative tracers in oncology provide detailed images of the metabolic and molecular characteristics of tumors, which are crucial for tailoring targeted therapies and monitoring responses, including radiotherapy. Notable advancements include programmed death ligand 1 (PD-L1)-targeting agents for lung cancer, prostate-specific membrane antigen-based tracers for prostate cancer, chemokine receptor-targeting agents for hematological malignancies, human epidermal growth factor receptor 2 (HER2)-targeting tracers for various cancers, Claudin 18 based tracers for epithelial tumors, glutamine tracers for colorectal cancer, and ascorbic acid analogs for assessing cancer metabolism and therapy efficacy. Additionally, novel tracers have been developed for non-neurological and non-oncological applications, including adrenal imaging, amyloidosis, and human immunodeficiency virus (HIV) infection. This overview focuses on the newly developed tracers, particularly those used in neurology and oncology.

PMID:39325320 | DOI:10.1007/s12149-024-01979-5

A brain-body feedback loop driving HPA-axis dysfunction in breast cancer

Fetched: October 16th, 2024, 2:00am UTC by Adrian Gomez

bioRxiv [Preprint]. 2024 Sep 14:2024.09.13.612923. doi: 10.1101/2024.09.13.612923.

ABSTRACT

Breast cancer patients often exhibit disrupted circadian rhythms in circulating glucocorticoids (GCs), such as cortisol. This disruption correlates with reduced quality of life and higher cancer mortality ^1-3 . The exact cause of this phenomenon - whether due to treatments, stress, age, co-morbidities, lifestyle factors, or the cancer itself remains unclear. Here, we demonstrate that primary breast cancer alone blunts host GC rhythms by disinhibiting neurons in the hypothalamus, and that circadian phase-specific neuromodulation of these neurons can attenuate tumor growth by enhancing anti-tumor immunity. We find that mice with mammary tumors exhibit blunted GC rhythms before tumors are palpable, alongside increased activity in paraventricular hypothalamic neurons expressing corticotropin-releasing hormone (i.e., PVN ^CRH neurons). Tumor-bearing mice have fewer inhibitory synapses contacting PVN ^CRH neurons and reduced miniature inhibitory post-synaptic current (mIPSC) frequency, leading to net excitation. Tumor-bearing mice experience impaired negative feedback on GC production, but adrenal and pituitary gland functions are largely unaffected, indicating that alterations in PVN ^CRH neuronal activity are likely a primary cause of hypothalamic-pituitary-adrenal (HPA) axis dysfunction in breast cancer. Using chemogenetics (hM3Dq) to stimulate PVN ^CRH neurons at different circadian phases, we show that stimulation just before the light-to-dark transition restores normal GC rhythms and reduces tumor progression. These mice have significantly more effector T cells (CD8+) within the tumor than non-stimulated controls, and the anti-tumor effect of PVN ^CRH neuronal stimulation is absent in mice lacking CD8+ T cells. Our findings demonstrate that breast cancer distally regulates neurons in the hypothalamus that control output of the HPA axis and provide evidence that therapeutic targeting of these neurons could mitigate tumor progression.

PMID:39314280 | PMC:PMC11419152 | DOI:10.1101/2024.09.13.612923

On Route to Chimeric Antigen Receptor T-cell (CAR T) Therapy, Less Is More: Adaptive Bridging Radiotherapy in Large B-cell Lymphoma

Fetched: October 16th, 2024, 2:00am UTC by Hazim Ababneh

Cureus. 2024 Aug 23;16(8):e67572. doi: 10.7759/cureus.67572. eCollection 2024 Aug.

ABSTRACT

CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has appreciably advanced treatment for relapsed or refractory large B-cell lymphoma (LBCL). During the critical interim of four to six weeks, until CAR T-cells are ready, radiation therapy (RT) can be used to control the disease. We present the case of a 64-year-old female with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who received adaptive RT for bilateral adrenal masses as a bridging strategy before undergoing CAR T-cell therapy and enrolled in an adaptive RT clinical trial. A plan was developed to deliver up to five once-weekly fractions (5 Gy per fraction) of CT-based online adaptive RT (Varian Ethos with HyperSight imaging, Varian Medical Systems, Palo Alto, CA). The patient experienced rapid symptomatic relief, with no RT-related toxicities. The patient received RT at only half of the sessions (two out of four sessions) due to excellent tumor shrinkage on cone-beam CT (CBCT). As such, the patient was treated at a lower total dose (10 Gy) than she otherwise would have received with standard RT. Post-RT PET/CT showed significant disease regression, compatible with partial response, prior to CAR T-cell infusion. This case shows the successful application of adaptive RT as bridging therapy prior to CAR T-cell therapy, and we expect the results of this adaptive RT trial to guide the future of adaptive RT in relapsed/refractory B-cell lymphomas.

PMID:39310556 | PMC:PMC11416816 | DOI:10.7759/cureus.67572

Permalink for 'Pheochromocytoma/Paraganglioma Syndrome Type 1 Presenting with Atypical Symptoms and a Novel Pathogenic Variant in the SDHD Gene: A Case Report'

Pheochromocytoma/Paraganglioma Syndrome Type 1 Presenting with Atypical Symptoms and a Novel Pathogenic Variant in the SDHD Gene: A Case Report

Fetched: October 16th, 2024, 2:00am UTC by Elham Zohrehvand

Arch Iran Med. 2024 Aug 1;27(8):447-451. doi: 10.34172/aim.28810. Epub 2024 Aug 1.

ABSTRACT

This case report presents a 10-year-old patient diagnosed with pheochromocytoma/paraganglioma syndrome type 1 (PPGL1), underlined by a novel heterozygous pathogenic variant (c.154_161del, p.ser52Profster14) in the SDHD gene. Initially, the patient manifested symptoms unusual for pheochromocytoma, including polyuria and polydipsia; however, further diagnostic investigations revealed a pheochromocytoma (PCC) tumor in the adrenal gland. Subsequently, whole exome sequencing (WES) test identified a pathogenic frameshift variant in the SDHD gene, strongly suggestive of PPGL1. This study highlights the importance of considering atypical symptoms in diagnosing rare pediatric pheochromocytoma/paraganglioma tumors and underscores the value of genetic testing in identifying underlying genetic causes, thereby facilitating personalized management of the condition.

PMID:39306716 | PMC:PMC11416696 | DOI:10.34172/aim.28810

Amino polycarboxylic acids-modified abiraterone derivatives as potential injectable anti-prostate cancer agents

Fetched: October 16th, 2024, 2:00am UTC by Na Zhu

Bioorg Chem. 2024 Sep 14;153:107824. doi: 10.1016/j.bioorg.2024.107824. Online ahead of print.

ABSTRACT

Abiraterone (Abi), an effective cytochrome oxidase P450 C17 (CYP17) inhibitor, inhibits androgen synthesis in testes, adrenal glands, and prostate tumors. However, their low bioavailability and dissolution rate due to their poor solubility and toxic side effects have hindered their clinical applications. In this study, water-soluble and injectable Abi derivatives were developed by introducing amino polycarboxylic acids into Abi, and their antiproliferation effects in vitro, mechanism of action, antitumor activities in vivo, pharmacokinetics, and toxicity were investigated. Compared to Abi, the water-soluble derivative Abi-DTPA exhibited excellent antitumor activity in vitro and in vivo. It decreased cell migration, invasion, and mitochondrial membrane potential. A mechanistic study revealed that it still targeted the CYP17 enzyme and increased the expression levels of apoptosis-related proteins, including cleaved caspase 9, cleaved PARP, and cleaved caspase 3. Abi-DTPA was the main form in the plasma and exhibited lower toxicity after intravenous administration. These findings suggest that Abi-DTPA can be used as a novel injectable anti-prostate cancer agent.

PMID:39305608 | DOI:10.1016/j.bioorg.2024.107824

The Incidence of Cancers in Patients With Nonfunctional Adrenal Tumors: A Swedish Population-Based National Cohort Study

Fetched: October 16th, 2024, 2:00am UTC by Jekaterina Patrova

J Endocr Soc. 2024 Sep 13;8(10):bvae154. doi: 10.1210/jendso/bvae154. eCollection 2024 Aug 27.

ABSTRACT

CONTEXT: It is unclear if nonfunctional adrenal tumors (NFAT) are associated with higher cancer incidence.

OBJECTIVE: To analyze the cancer incidence in patients with NFAT.

METHODS: In this national register-based retrospective cohort study, consecutive patients with NFAT identified in Sweden 2005-2019 and matched control individuals without adrenal tumors were followed up to 15 years. Outcome data were collected from national registers and adjusted for confounders. Both cases and controls were followed until newly diagnosed malignancy, death, or until 2019. Individuals with adrenal hormonal excess or prior malignancy were excluded.

RESULTS: Among 17 726 cases, 10 777 (60.8%) were women, and the median age was 65 (IQR, 57-73) years. Among 124 366 controls, 69 514 (55.9%) were women, and the median age was 66 (IQR, 58-73) years. The incidence of any cancer was higher in patients with NFAT compared to controls (hazard ratio [HR] 1.35 95% CI 1.29-1.40; adjusted HR 1.31, 95% CI 1.26-1.37). NFAT was associated with a higher incidence of adrenal, thyroid, lung, stomach and small intestine, kidney, pancreatic, breast, and colorectal cancer. Sensitivity analyses did not change the overall results, but associations were not significantly increased after adjustment in patients with NFAT and appendicitis or gallbladder/biliary tract/pancreas disorders. Cancer incidence may have been underestimated by adjusting for unclear and benign tumors.

CONCLUSION: The incidence of cancer was increased in patients with NFAT. Long-term follow-up may be indicated.

PMID:39301313 | PMC:PMC11411210 | DOI:10.1210/jendso/bvae154

Unlocking the secrets of metabolic syndrome: retroperitoneal fat area as a novel predictor

Fetched: October 16th, 2024, 2:00am UTC by O A Savas

Eur Rev Med Pharmacol Sci. 2024 Sep;28(17):4255-4263. doi: 10.26355/eurrev_202409_36714.

ABSTRACT

OBJECTIVE: Metabolic syndrome (MetS) affects about one-fourth of the global adult population and is characterized by hyperglycemia, abdominal obesity, low HDL (high-density lipoprotein cholesterol) cholesterol, and high triglycerides and blood pressure. Its emergence in developed nations is linked to energy intake imbalances and sedentary lifestyles. There is a parallel between MetS and conditions marked by glucocorticoid excess, such as Cushing's syndrome (CS), sharing features like central obesity, hypertension, dyslipidemia, and insulin resistance. This study aimed to investigate the association between retroperitoneal fat area (RFA) and MetS components in patients undergoing laparoscopic lateral transabdominal adrenalectomy. While intra-abdominal visceral fat's role in MetS has been studied, the significance of RFA needs further exploration.

PATIENTS AND METHODS: The research involved 88 patients categorized into three groups: adrenal-dependent CS, subclinical CS (SCS), and nonfunctional adrenal incidentaloma (NFA). Parameters, including body mass index (BMI), RFA, waist circumference, blood pressure, lipid profile, and fasting glucose levels, were measured. The study used hormonal hypersecretion assessments, criteria for SCS diagnosis, and biochemical analyses. MetS components were determined based on established criteria, and RFA quantification used advanced imaging software on computed tomography (CT) scans. Previous studies on intra-abdominal fat and MetS were reviewed to contextualize the findings.

RESULTS: Patients with MetS had significantly higher BMI, waist circumference, and RFA compared to those without MetS. Positive correlations were observed between BMI, RFA, central obesity, and MetS. ROC curve analysis showed a significant relationship between RFA and MetS, with a cutoff value of 36.6 cmÂ² predicting MetS accurately in 95% of cases. The results were compared with existing literature on visceral fat's impact on MetS.

CONCLUSIONS: The study findings underscore the associations between anthropometric parameters, specifically RFA and MetS. RFA is a valuable tool for assessing metabolic risk, with implications for refining criteria for adrenalectomy in individuals with adrenal incidentalomas.

PMID:39297594 | DOI:10.26355/eurrev_202409_36714

Adrenal Insufficiency in Children

Fetched: October 16th, 2024, 2:00am UTC by Marissa J. Kilberg

2024 Oct 2. In: Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, de Herder WW, Dhatariya K, Dungan K, Hofland J, Kalra S, Kaltsas G, Kapoor N, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, LaferrÃ¨re B, Levy M, McGee EA, McLachlan R, New M, Purnell J, Sahay R, Shah AS, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000â€“.

ABSTRACT

Adrenal insufficiency (AI) is an uncommon but potentially life-threatening condition related to impaired secretion of cortisol by the adrenal gland. In general, this condition can be divided into primary (adrenal failure) and central (hypothalamic/pituitary) causes. In this chapter, we categorize the causes of adrenal insufficiency and systematically review the etiologies and associations to guide the laboratory evaluation and treatment, specifically as it pertains to the pediatric patient. Early diagnosis and treatment can prevent the development of adrenal crisis â€“ prompt recognition can be lifesaving. Understanding the manifestation of unique types of adrenal insufficiency can guide management with glucocorticoid +/- mineralocorticoids and guide further investigation for associated disorders. We discuss the treatment of adrenal insufficiency, reviewing both the acute (crisis) and chronic management. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:39401306 | Bookshelf:NBK608067

Development and Microscopic Anatomy of the Pituitary Gland

Fetched: October 16th, 2024, 2:00am UTC by Ian S. Scott

2024 Sep 28. In: Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, de Herder WW, Dhatariya K, Dungan K, Hofland J, Kalra S, Kaltsas G, Kapoor N, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, LaferrÃ¨re B, Levy M, McGee EA, McLachlan R, New M, Purnell J, Sahay R, Shah AS, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000â€“.

ABSTRACT

The pituitary gland is an organ of dual origin. The anterior part (adenohypophysis) arises from embryonic buccal mucosa, whereas the posterior part (neurohypophysis) derives from neural ectoderm. Precise spatial and temporal co-ordination of transcription factor expression in both structures is critical for pituitary gland formation and the differentiation of hormone-producing cells. Disruption of this regulation, for instance by transcription factor mutation, can lead to numerous developmental disorders and disturbances in endocrine function and regulation. We provide an overview of the molecular drivers of pituitary organogenesis and illustrate the anatomy and histology of the mature pituitary gland, comprising adenohypophysis (anterior lobe), neurohypophysis (posterior lobe), pars intermedia (intermediate lobe), and infundibulum (pituitary stalk). For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:28402619 | Bookshelf:NBK425703

Infections Of The Hypothalamic-Pituitary Region

Fetched: October 16th, 2024, 2:00am UTC by Sandra Pekic

2024 Sep 27. In: Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, de Herder WW, Dhatariya K, Dungan K, Hofland J, Kalra S, Kaltsas G, Kapoor N, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, LaferrÃ¨re B, Levy M, McGee EA, McLachlan R, New M, Purnell J, Sahay R, Shah AS, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000â€“.

ABSTRACT

Infections of the hypothalamic-pituitary region are rare lesions, accounting for less than 1% of all pituitary lesions. The clinical diagnosis of these infections can be difficult due to the nonspecific nature of the disease (in many patients without symptoms of infection) and may be misdiagnosed as other pituitary lesions. The risk factors for infections of the hypothalamic-pituitary region are meningitis, paranasal sinusitis, head surgery, and immunocompromised host (diabetes mellitus, Cushingâ€™s syndrome, HIV infections, solid organ transplantation, malignancy). Infections can develop in a normal pituitary gland or in pre-existing pituitary lesions (adenoma, RathkeÂ´s cleft cyst, craniopharyngioma). There are several modes of dissemination of the infection to the hypothalamic-pituitary region: hematogenous, iatrogenic (after neurosurgical procedures), and spread from paranasal or nasal cavity (through venous channels of the sphenoid bone). Hypothalamic-pituitary infections most commonly present with visual disturbances and headache, in some cases with fever and leukocytosis. A significant proportion of patients develop hypothalamic-pituitary dysfunction during the acute phase of the disease or months and years after successful antimicrobial therapy. Diagnosis can be challenging and the hypothalamic-pituitary infection with formation of abscess or granuloma may be misdiagnosed as a pituitary tumor. Transsphenoidal drainage followed by antibiotics, antimycotics, or anti-tuberculous drugs are usually efficient in successful treatment of these patients. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:30321013 | Bookshelf:NBK532083

Gravesâ€™ Disease and the Manifestations of Thyrotoxicosis

Fetched: October 16th, 2024, 2:00am UTC by David Toro-Tobon

2024 Sep 24. In: Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, de Herder WW, Dhatariya K, Dungan K, Hofland J, Kalra S, Kaltsas G, Kapoor N, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, LaferrÃ¨re B, Levy M, McGee EA, McLachlan R, New M, Purnell J, Sahay R, Shah AS, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000â€“.

ABSTRACT

Graves' disease (GD) is an autoimmune disorder characterized by hyperthyroidism and various systemic manifestations, including thyroid eye disease (TED) and, less commonly, dermopathy. This chapter provides an in-depth review of GD, covering its history, epidemiology, risk factors, and the molecular mechanisms underlying autoimmune hyperthyroidism. Emphasis is placed on emerging insights into the genetic, environmental, and immunological factors contributing to GD's multifactorial pathogenesis. The chapter also explores the pathogenic role of TSH receptor antibodies and their significance in diagnosis and treatment, alongside key clinical features of thyrotoxicosis. For complete coverage of all related areas of Thyroidology please visit our Free web-site https://www.thyroidmanager.org. For complete coverage of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:25905422 | Bookshelf:NBK285567

Familial Hypercholesterolemia: Genes and Beyond

Fetched: October 16th, 2024, 2:00am UTC by Bruce A. Warden

2024 Sep 23. In: Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, de Herder WW, Dhatariya K, Dungan K, Hofland J, Kalra S, Kaltsas G, Kapoor N, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, LaferrÃ¨re B, Levy M, McGee EA, McLachlan R, New M, Purnell J, Sahay R, Shah AS, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000â€“.

ABSTRACT

Genetic disorders resulting in familial hypercholesterolemia (FH) include autosomal dominant hypercholesterolemia (ADH), polygenic hypercholesterolemia, as well as other rare conditions such as autosomal recessive hypercholesterolemia (ARH). All of these disorders cause elevations in low-density lipoprotein (LDL)-cholesterol (LDL-C) and, as a result, greatly increase the risk of cardiovascular disease (CVD). Genetic loci involved in ADH include the LDLR, which codes for the LDL receptor (LDLR), APOB, which codes for apolipoprotein B-100 (apoB-100), the major protein component of LDL, PCSK9, which codes for Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9), the low abundance circulatory protein that terminates the lifecycle of the LDLR, and apolipoprotein E (APOE), which is an important constituent of triglyceride rich lipoproteins. Importantly, a large percentage of people with the severe hypercholesterolemic phenotype do not possess a readily identifiable gene defect and many likely have polygenic hypercholesterolemia. Thus, identification of a specific genetic pathologic variant is not a necessary condition for the diagnosis of a genetic hypercholesterolemia. Several formal diagnostic criteria exist for FH and include lipid levels, family history, personal history, physical exam findings, and genetic testing. As all individuals with severe hypercholesterolemia are at high risk for CVD, treatment is centered on dietary and lifestyle modifications and early institution of lipid-lowering pharmacotherapy. Treatment should initially be statin-based, but most patients require adjunctive medications such as ezetimibe and PCSK9 blocking monoclonal antibodies. Three large cardiovascular outcome trials have shown a reduction in atherosclerotic CVD when ezetimibe or PCSK9 blocking monoclonal antibodies were added to a background of statin therapy and consequently have assisted in shaping international guidelines and consensus recommendations. Novel therapeutics recently developed, include: inclisiran â€“ a small interfering ribonucleic acid (siRNA)-based gene-silencing technology that inhibits PCSK9 production, bempedoic acid â€“ an inhibitor of adenosine triphosphate (ATP)-citrate lyase with a large cardiovascular outcome trial demonstrating a reduction in CVD in patients with statin intolerance and is now FDA approved for a wide range of patients including heterozygous FH and patients with prior CVD (secondary prevention) or those at high-risk for CVD (primary prevention) and elevated LDL-C, and evinacumab â€“ a fully human monoclonal antibody inhibiting angiopoietin-like 3 (ANGPTL3) (FDA approved for homozygous FH only). Patients with extreme and unresponsive elevations in LDL-C will require more aggressive therapies such as lipoprotein apheresis and agents for the treatment of severe hypercholesterolemia such as microsomal triglyceride transfer protein (MTP) inhibitors and evinacumab. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:26844336 | Bookshelf:NBK343488

Lipodystrophy Syndromes: Presentation and Treatment

Fetched: September 4th, 2024, 2:00am UTC by Baris Akinci

2024 Aug 21. In: Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, de Herder WW, Dhatariya K, Dungan K, Hofland J, Kalra S, Kaltsas G, Kapoor N, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, LaferrÃ¨re B, Levy M, McGee EA, McLachlan R, New M, Purnell J, Sahay R, Shah AS, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000â€“.

ABSTRACT

Lipodystrophy syndromes are a heterogeneous group of diseases, characterized by selective absence of adipose tissue. In one sense, these diseases are lipid-partitioning disorders, where the primary defect is the loss of functional adipocytes, leading to ectopic steatosis, severe dyslipidemia, and insulin resistance. These syndromes have attracted significant attention since the mid-1990s as the understanding of adipose tissue biology grew, initially spurred by the discovery of the pathways leading to adipocyte differentiation and maturation, and then by the discovery of leptin. Although lipodystrophy syndromes are known since the beginning of the 20th century, significant progress in understanding these syndromes were made in the last two decades, placing these syndromes at the forefront of the translational metabolism field. Currently, more than 20 distinctive molecular etiologies have been attributed to cause human diseases most of which map to adipocyte differentiation or lipid droplet pathways. Seemingly acquired syndromes are recently reported to have a genetic basis, suggesting that our â€œpre-genomeâ€ understanding of the syndromes was inadequate and that we need to likely change our classification schemes. Regardless of the etiology, it is the selective absence of adipose tissue and its function, leading to the reduced ability to store long-term energy that perturbs insulin sensitivity and lipid metabolism. The treatment of these syndromes has also attracted considerable interest. The most successful example of the treatment of these syndromes came from the demonstration that leptin replacement strategy improved insulin resistance and dyslipidemia in the most severely affected forms of the disease, leading to an FDA approved therapy for generalized lipodystrophy syndromes. In the partial forms of the disease, the phenotypes are more complex, and the efficacy of leptin is not as uniform. Currently, standard treatment-resistant partial lipodystrophy is an EMA-approved indication, and numerous trials are in progress, either evaluating the efficacy of leptin in familial partial lipodystrophy or aiming to develop potential new treatments for the partial forms of the disease. These rare metabolic diseases are likely to continue to fuel novel breakthroughs in the field of metabolism in the foreseeable future. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:29989768 | Bookshelf:NBK513130

Adrenal tumours in patients with pathogenic APC mutations: a retrospective study

Fetched: September 4th, 2024, 2:00am UTC by Lyman Lin

Hered Cancer Clin Pract. 2024 Sep 3;22(1):17. doi: 10.1186/s13053-024-00289-1.

ABSTRACT

BACKGROUND: Adrenal tumours are associated with familial adenomatous polyposis (FAP). In the literature, most studies use the clinical definition of FAP (more than 100 adenomatous polyps found in endoscopic studies). However, not all patients that meet clinical criteria for FAP carry pathogenic mutations in the adenomatous polyposis coli (APC) gene, as there is genetic heterogeneity responsible for FAP with the polyposis sometimes explained by genetic and environmental factors other than pathogenic APC mutations. Reciprocally, not all the patients with pathogenic APC variants will fulfil the classic criteria of FAP.

OBJECTIVE: This study aims to investigate the characteristics of adrenal tumours in patients with pathogenic or likely pathogenic APC variants and explore the hormonal function of these patients.

METHOD: This is a retrospective cohort study. Patients with pathogenic or likely pathogenic APC variants were recruited and their radiological assessments were reviewed. Patient demographic data, APC variants, adrenal mass characteristics and hormonal testing results were collected.

RESULT: The prevalence of adrenal mass was 26.7% (24/90) among patients with pathogenic or likely pathogenic APC variants. Using the classic definition, the prevalence was 32.4% (22/68). Four patients had adrenal hormone testing, two of which had Conn's syndrome and two had nonspecific subclinical results.

CONCLUSION: In our cohort, the prevalence of adrenal tumours among patients with pathogenic and likely pathogenic APC mutations is at least twice to three times higher than the general population prevalence reported from international population-based studies. The hormonal functions of patients with pathogenic APC variants and adrenal tumours can be investigated with routine testing in further research.

PMID:39227904 | DOI:10.1186/s13053-024-00289-1

Kidney sparing during surgical treatment of an adrenocortical carcinoma with renal vein invasion in a cat

Fetched: September 3rd, 2024, 2:00am UTC by Stefano Nicoli

Can Vet J. 2024 Sep;65(9):894-899.

ABSTRACT

A 15-year-old domestic shorthair cat was presented with gastrointestinal signs, polyuria, polydipsia, and weakness. Abdominal bruit ("whooshing" sound from turbulent blood flow) and hypertension (systolic blood pressure: 200 mmHg) were present. A left adrenal gland mass was detected with abdominal ultrasonography; a subsequent CT examination identified a mass and a thrombus in the ipsilateral renal vein. Adrenalectomy and venotomy were completed but nephrectomy was not necessary. Histological diagnosis was an adrenocortical carcinoma. There were no clinical signs at a follow-up examination 30 mo after surgery. Key clinical message: This report describes successful surgical management of feline adrenocortical carcinoma with renal vein invasion without kidney damage. This case suggests that, after correct diagnosis and in well-selected cases, surgery to remove adrenal tumors and thrombi in cats, despite renal vein invasion, can be done with excellent short- and long-term outcomes.

PMID:39219601 | PMC:PMC11339906

Permalink for 'Multimodal Treatment With Nivolumab Contributes to Long-Term Survival in a Case of Unresectable Esophagogastric Junction Neuroendocrine Carcinoma'

Multimodal Treatment With Nivolumab Contributes to Long-Term Survival in a Case of Unresectable Esophagogastric Junction Neuroendocrine Carcinoma

Fetched: September 3rd, 2024, 2:00am UTC by Shunya Hanzawa

Cureus. 2024 Aug 1;16(8):e65981. doi: 10.7759/cureus.65981. eCollection 2024 Aug.

ABSTRACT

Advanced neuroendocrine carcinoma (NEC) has an extremely poor prognosis, partly explained by the rarity and diagnostic difficulty, for which the most appropriate treatment strategy has not been established. In this report, we discuss a case of unresectable advanced esophagogastric junction NEC, which was difficult to diagnose, that has achieved relatively long-term survival with multidisciplinary treatment centered on nivolumab. A man in his 60s was initially diagnosed with an advanced esophagogastric junction squamous cell carcinoma (SCC). The lymph node metastasis was detected in the regional lymph nodes and para-aortic region. We diagnosed the patient with T3, N3, M1 (Lym), stage IVB, and administered systemic chemotherapy. Due to the failure of first-line, fluorouracil, and cisplatin therapy, we administered nivolumab as the second-line therapy. This therapy demonstrated partial response, so we performed conversion surgery, however the postoperative diagnosis was NEC. Three years after treatment initiation, a single lymph node metastasis has recurred, which is under control with nivolumab and radiation therapy. However, 4.5 years after the start of treatment, with the advent of immune-related adverse events (irAE), nivolumab was discontinued and the patient was placed on surveillance. Six months after that, metastasis to the hilar lymph node and adrenal gland was observed. Both times that recurrence/metastasis appeared, they occurred while nivolumab was being discontinued, suggesting its significant systemic anti-cancer effect. Therefore, nivolumab in particular may be an effective treatment for advanced esophageal NEC, and this case suggests that it may contribute to prolonged progression-free survival.

PMID:39221328 | PMC:PMC11366065 | DOI:10.7759/cureus.65981

Permalink for 'From cortisol-producing adrenal adenoma to atrial myxoma, through nivolumab-induced hypophysitis: a complicated case report of Carney Complex'

From cortisol-producing adrenal adenoma to atrial myxoma, through nivolumab-induced hypophysitis: a complicated case report of Carney Complex

Fetched: September 2nd, 2024, 2:00am UTC by Ludovico Di Gioia

Endocrine. 2024 Sep 1. doi: 10.1007/s12020-024-03997-9. Online ahead of print.

ABSTRACT

PURPOSE: Carney complex (CNC) is a rare, autosomal dominant syndrome, most commonly caused by PRKAR1A gene mutations and characterized by pigmented skin and mucosal changes with multiple endocrine and non-endocrine tumours. This case report highlights the diagnostic challenges associated with CNC in a patient with multiple neoplasms and a complex medical history, including cortisol-producing adrenal adenoma, breast cancer, melanoma, and atrial myxoma.

METHODS: We report the case of a 41-year-old woman with a medical history of left adrenalectomy for cortisol producing adenoma (2005) with no sign of adrenal insufficiency at follow-up, right mastectomy for BRCA1/2 negative carcinoma (2013) and left parotid BRAF-V600E wild-type melanoma (2019), treated with nivolumab adjuvant therapy. In August 2019, following the fifth nivolumab administration, the patient developed central hypocortisolism due to iatrogenic hypophysitis, confirmed by brain MRI and properly treated with oral hydrocortisone. Nivolumab was discontinued due to the patient's decision. In October 2020 and April 2021, the patient had ischaemic strokes, requiring systemic thrombolysis. Echocardiographic examination then revealed a left atrial mass, with histological finding of myxoma.

RESULTS: Given the rarity of this neoplasm and the suspicion of a syndromic disorder, a genetic evaluation was conducted, which confirmed a PRKAR1A gene mutation and the diagnosis of Carney complex.

CONCLUSION: This case illustrates the diagnostic challenges in CNC, especially in patients with multiple tumourous manifestations and a wide spectrum of life-threatening clinical presentations. It underscores the importance of a multidisciplinary approach to diagnose and manage rare diseases, improving patient outcomes through timely genetic testing and coordinated care.

PMID:39217593 | DOI:10.1007/s12020-024-03997-9

Joint single-cell genetic and transcriptomic analysis reveal pre-malignant SCP-like subclones in human neuroblastoma

Fetched: September 2nd, 2024, 2:00am UTC by Thale K Olsen

Mol Cancer. 2024 Aug 31;23(1):180. doi: 10.1186/s12943-024-02091-y.

ABSTRACT

BACKGROUND: Neuroblastoma (NB) is a heterogeneous embryonal malignancy and the deadliest tumor of infancy. It is a complex disease that can result in diverse clinical outcomes. In some children, tumors regress spontaneously. Others respond well to existing treatments. But for the high-risk group, which constitutes approximately 40% of all patients, the prognosis remains dire despite collaborative efforts in basic and clinical research. While its exact cellular origin is still under debate, NB is assumed to arise from the neural crest cell lineage including multipotent Schwann cell precursors (SCPs), which differentiate into sympatho-adrenal cell states eventually producing chromaffin cells and sympathoblasts.

METHODS: To investigate clonal development of neuroblastoma cell states, we performed haplotype-specific analysis of human tumor samples using single-cell multi-omics, including joint DNA/RNA sequencing of sorted single cells (DNTR-seq). Samples were also assessed using immunofluorescence stainings and fluorescence in-situ hybridization (FISH).

RESULTS: Beyond adrenergic tumor cells, we identify subpopulations of aneuploid SCP-like cells, characterized by clonal expansion, whole-chromosome 17 gains, as well as expression programs of proliferation, apoptosis, and a non-immunomodulatory phenotype.

CONCLUSION: Aneuploid pre-malignant SCP-like cells represent a novel feature of NB. Genetic evidence and tumor phylogeny suggest that these clones and malignant adrenergic populations originate from aneuploidy-prone cells of migrating neural crest or SCP origin, before lineage commitment to sympatho-adrenal cell states. Our findings expand the phenotypic spectrum of NB cell states. Considering the multipotency of SCPs in development, we suggest that the transformation of fetal SCPs may represent one possible mechanism of tumor initiation in NB with chromosome 17 aberrations as a characteristic element.

PMID:39217332 | PMC:PMC11365129 | DOI:10.1186/s12943-024-02091-y

Immunotherapy and PD-L1 Tumor Expression in Moroccan Non-Small Cell Lung Cancer Patients with Various Metastasis

Fetched: September 1st, 2024, 2:00am UTC by Oussama Aazzane

Asian Pac J Cancer Prev. 2024 Aug 1;25(8):2841-2852. doi: 10.31557/APJCP.2024.25.8.2841.

ABSTRACT

INRODUCTION: The question of whether tumor expression of PD-L1 and the presence of distant metastasis could influence the efficacy of immunotherapy represents a major challenge and needs to be further elucidated. The aim of this study is to evaluate the predictive significance of tumor expression of PD-L1 as well as the number and site of metastasis in non-small cell lung cancer (NSCLC) among Moroccan patients treated with immunotherapy.

MATERIAL AND METHODS: Between January 2019 and February 2023, we recruited Moroccan patients with metastatic NSCLC. All were treated with immunotherapy, either as monotherapy or in combination with chemotherapy. Immunohistochemistry was used to assess PD-L1 (clone 22C3) and ALK (clone D5F3) status. EGFR status was established by qPCR. Tumor PD-L1 expression was classified into 2 levels: TPS <1% (negative expression) and TPS â‰¥1% (positive expression). Statistical analysis was performed using SPSS Statistics V.21 software.

RESULTS: The median age of patients (N=40) was 67 years (39- 92 years) and the sex ratio was 9. Disease dissemination revealed that 22.5% (N=9) of patients had a metastatic burden â‰¥ 3 (MBâ‰¥3). As for the sites of metastasis, the results showed that 20% (N=8), 10% (N=4), 42.5% (N=17), 22.5% (N=9), 27.5% (N=11), 45% (N=18) and 27.5% (N=11) of patients had developed lymph node, liver, bone, brain, pleural, contralateral lung and adrenal metastasis respectively. Positive PD-L1 expression was significantly associated with shorter overall survival (OS = 17.19 vs. 28.85 months, p=0.01). High metastatic burden (MB â‰¥ 3) was associated with lower objective response rate (ORR), shorter progression-free survival (PFS), and reduced OS, respectively (ORR = 0 vs. 58.06%, p=0.002; PFS = 10.23 vs. 25.27 months, p=0.001; and OS = 11.60 vs. 27.91 months, p=0.003). Only the presence of osseous metastasis was significantly associated with lower ORR, shorter PFS, and OS compared to other metastatic locations (ORR = 5.88 vs. 73.9%, p=0.000; PFS = 10.72 vs. 31.33 months, p=0.000; and OS = 11.39 vs. 36.17 months, p=0.000). Finally, the presence of hepatic metastasis was significantly associated with shorter PFS (10.75 months) compared to those without hepatic metastasis (22.53 months) (p=0.046). Finally, the results of the multivariate analysis revealed that the presence of bone metastasis was strongly correlated with a significant decrease in progression-free survival (p=0.001) as well as overall survival (p=0.002).

CONCLUSION: Our results suggest that tumor expression of PD-L1 and metastatic burden should play a significant role in predicting the response to immunotherapy. Furthermore, it is important to note that the presence of osseous and hepatic metastasis could negatively influence the clinical outcomes of immunotherapy.

PMID:39205582 | DOI:10.31557/APJCP.2024.25.8.2841

Expression Patterns of MOTS-c in Adrenal Tumors: Results from a Preliminary Study

Fetched: September 1st, 2024, 2:00am UTC by Kacper KamiÅ„ski

Int J Mol Sci. 2024 Aug 9;25(16):8721. doi: 10.3390/ijms25168721.

ABSTRACT

Adrenal tumors, such as adrenocortical carcinoma (ACC), adrenocortical adenoma (ACA), and pheochromocytoma (PCC) are complex diseases with unclear causes and treatments. Mitochondria and mitochondrial-derived peptides (MDPs) are crucial for cancer cell survival. The primary aim of this study was to analyze samples from different adrenal diseases, adrenocortical carcinoma, adrenocortical adenoma, and pheochromocytoma, and compare them with normal adrenal tissue to determine whether the expression levels of the mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c) gene and protein vary between different types of adrenal tumors compared to healthy controls using qPCR, ELISA, and IHC methods. Results showed decreased MOTS-c mRNA expression in all adrenal tumors compared to controls, while serum MOTS-c protein levels increased in ACA and PCC but not in ACC. The local distribution of MOTS-c protein in adrenal tissue was reduced in all tumors. Notably, MOTS-c protein expression declined with ACC progression (stages III and IV) but was unrelated to patient age or sex. Tumor size and testosterone levels positively correlated with MOTS-c mRNA but negatively with serum MOTS-c protein. Additionally, serum MOTS-c protein correlated positively with glucose, total cholesterol, HDL, LDL, and SHGB levels. These findings suggest disrupted expression of MOTS-c in the spectrum of adrenal diseases, which might be caused by mechanisms involving increased mitochondrial dysfunction and structural changes in the tissue associated with disease progression. This study provides a detailed examination of MOTS-c mRNA and protein in adrenal tumors, indicating the potential role of MDPs in tumor biology and progression.

PMID:39201408 | PMC:PMC11354279 | DOI:10.3390/ijms25168721

Role of Different Variants of Leptin Receptor in Human Adrenal Tumor Types

Fetched: September 1st, 2024, 2:00am UTC by Anna Klimont

Int J Mol Sci. 2024 Aug 9;25(16):8682. doi: 10.3390/ijms25168682.

ABSTRACT

The aim of the study was to evaluate the diagnostic and prognostic significance of leptin receptor isoforms in adrenal tumors. In a single-center study, 96 patients (19 with adrenal cortical carcinoma and 77 with benign tumors) underwent an adrenalectomy. A total of 14 unaffected adrenal gland tissues from kidney donors were used as controls. Fasting blood samples were collected for laboratory tests, and mRNA expressions of leptin receptor isoforms were assessed by RT-qPCR. The study analyzed correlations between mRNA expressions and clinical data and measured NCI-H295R cell proliferation via a real-time cell analyzer. All adrenal lesions expressed leptin receptor isoforms. Significantly lower LepR1 expression was observed in carcinoma tissues than in adenomas and controls (p = 0.016). Expressions of LepR3&LepR6 were correlated with overall survival (p = 0.036), while LepR2&LepR4 and LepR5 expressions were inversely related to morning serum cortisol levels (p = 0.041). Leptin reduced NCI-H295R cell proliferation (p < 0.0001). The study highlights the diagnostic and prognostic significance of leptin receptor isoforms in adrenal tumors. Specifically, LepR1 may serve as a diagnostic marker for carcinomas, while LepR3&LepR6 have potential use as prognostic markers.

PMID:39201370 | PMC:PMC11354735 | DOI:10.3390/ijms25168682

Permalink for 'Utility of Adrenal Vein Sampling With and Without Ultra-Low Dose ACTH Infusion in the Diagnostic Evaluation of Primary Aldosteronism'

Utility of Adrenal Vein Sampling With and Without Ultra-Low Dose ACTH Infusion in the Diagnostic Evaluation of Primary Aldosteronism

Fetched: September 1st, 2024, 2:00am UTC by Christopher A Preston

Endocrinol Diabetes Metab. 2024 Sep;7(5):e70001. doi: 10.1002/edm2.70001.

ABSTRACT

BACKGROUND: Adrenal vein sampling (AVS), integral to identifying surgically remediable unilateral primary aldosteronism (PA), is technically challenging and subject to fluctuations in cortisol and aldosterone secretion. Intra-procedural adrenocorticotropic hormone (ACTH), conventionally administered as a 250-Î¼g bolus and/or 50 Î¼g per hour infusion, increases cortisol and aldosterone secretion and can improve AVS success, but may cause discordant lateralisation compared to unstimulated AVS.

AIMS: To assess if AVS performed with ultra-low dose ACTH infusion causes discordant lateralisation.

METHODS: Here, we describe our preliminary experience using an ultra-low dose ACTH infusion AVS protocol. We retrospectively reviewed the results of consecutive AVS procedures (n = 37) performed with and without ultra-low dose ACTH (1-Î¼g bolus followed by 1.25 Î¼g per hour infusion).

RESULTS: Bilateral AV cannulation was successful in 70% of procedures pre-ACTH and 89% post-ACTH (p < 0.01). Sixty-nine percent of studies lateralised pre-ACTH and 55% post-ACTH, improving to 79% when both groups were combined. Lateralisation was discordant in 11 cases, including eight in which lateralisation was present only on basal sampling, and three in which lateralisation occurred only with ACTH stimulation.

DISCUSSION: Overall, the decrease in lateralisation rates with ACTH was higher than previously reported for some protocols utilising conventional doses of ACTH. Our results suggest that AVS performed with ultra-low dose ACTH can cause discordant lateralisation similar to AVS performed with conventional doses of ACTH.

CONCLUSION: Prospective studies directly comparing low and conventional dose ACTH AVS protocols and long-term patient outcomes are needed to help define the optimal ACTH dose for accurate PA subtyping.

PMID:39207956 | PMC:PMC11361314 | DOI:10.1002/edm2.70001

Elevated 131I Activity in Adrenal Cyst in a Patient With Thyroid Cancer

Fetched: August 29th, 2024, 2:00am UTC by Wei Liu

Clin Nucl Med. 2024 Oct 1;49(10):959-961. doi: 10.1097/RLU.0000000000005405.

ABSTRACT

A 23-year-old man with papillary thyroid cancer underwent radioiodine ( 131 I) treatment following total thyroidectomy and node dissection. Posttreatment 131 I SPECT/CT images revealed an additional focus of increased 131 I activity in the left adrenal gland, raising suspicion for possible adrenal metastasis. Ultimately, pathological examination confirmed the diagnosis of an adrenal cyst.

PMID:39192512 | DOI:10.1097/RLU.0000000000005405

Research progress of KCNJ5 gene in aldosterone-producing adenoma

Fetched: August 29th, 2024, 2:00am UTC by Guan-Jun Jia

Sheng Li Xue Bao. 2024 Aug 25;76(4):587-596.

ABSTRACT

Aldosterone-producing adenoma is a subtype of primary aldosteronism. Recent advancements in multi-omics research have led to significant progress in understanding primary aldosteronism at the genetic level. Among the various genes associated with the development of aldosterone-producing adenomas, the KCNJ5 (potassium inwardly rectifying channel, subfamily J, member 5) gene has received considerable attention due to its prevalence as the most common somatic mutation gene in primary aldosteronism. This paper aims to integrate the existing evidence on the involvement of KCNJ5 gene in the pathogenesis of aldosterone-producing adenomas, to enhance the understanding of the underlying mechanisms of aldosterone-producing adenomas from the perspective of genetics, and to provide novel insights for the clinical diagnosis and treatment of aldosterone-producing adenomas.

PMID:39192791

Integrative genomic analyses identify neuroblastoma risk genes involved in neuronal differentiation

Fetched: August 28th, 2024, 2:00am UTC by Matilde Tirelli

Hum Genet. 2024 Aug 27. doi: 10.1007/s00439-024-02700-2. Online ahead of print.

ABSTRACT

Genome-Wide Association Studies (GWAS) have been decisive in elucidating the genetic predisposition of neuroblastoma (NB). The majority of genetic variants identified in GWAS are found in non-coding regions, suggesting that they can be causative of pathogenic dysregulations of gene expression. Nonetheless, pinpointing the potential causal genes within implicated genetic loci remains a major challenge. In this study, we integrated NB GWAS and expression Quantitative Trait Loci (eQTL) data from adrenal gland to identify candidate genes impacting NB susceptibility. We found that ZMYM1, CBL, GSKIP and WDR81 expression was dysregulated by NB predisposing variants. We further investigated the functional role of the identified genes through computational analysis of RNA sequencing (RNA-seq) data from single-cell and whole-tissue samples of NB, neural crest, and adrenal gland tissues, as well as through in vitro differentiation assays in NB cell cultures. Our results indicate that dysregulation of ZMYM1, CBL, GSKIP, WDR81 may lead to malignant transformation by affecting early and late stages of normal program of neuronal differentiation. Our findings enhance the understanding of how specific genes contribute to NB pathogenesis by highlighting their influence on neuronal differentiation and emphasizing the impact of genetic risk variants on the regulation of genes involved in critical biological processes.

PMID:39192051 | DOI:10.1007/s00439-024-02700-2

Primary adrenal sarcomas: A national analysis of epidemiological trends, treatment patterns, and outcomes

Fetched: August 28th, 2024, 2:00am UTC by Bibek Aryal

J Surg Oncol. 2024 Aug 27. doi: 10.1002/jso.27836. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Primary adrenal sarcoma (PAS) is an exceedingly rare malignancy with limited data available on its epidemiology, management, and outcomes. This study aimed to characterize the national incidence, treatment patterns, and survival of PAS utilizing a National Cancer Database.

METHODS: The National Cancer Database was queried for patients diagnosed with primary adrenal tumors from 2004 to 2019. Cases with sarcoma histology were identified as PAS. Annual incidence trends, histological distribution, treatment modalities (surgery, chemotherapy, radiation therapy), perioperative outcomes, and overall survival (OS) were analyzed.

RESULTS: Of 7213 primary adrenal tumor cases, 332 (4.6%) were PAS. The most common histological subtypes were leiomyosarcoma (37.3%), hemangiosarcoma (27.1%), and sarcoma not otherwise specified (6.0%). Most cases (71.7%) presented as locoregional disease. Treatment included surgery alone (47.8%), surgery plus chemotherapy and/or radiation (27.1%), chemotherapy/radiation alone (13.3%), or no treatment (13.9%). For surgical cases, the median length of stay was 5 days, the 30-day readmission rate was 3.36%, and the 30/90-day mortality rates were 3.65% and 9.90%, respectively. The 5-year OS rate for surgery alone was 43%, with a median OS of 34.6 months. For surgery with radiation/chemotherapy, the 5-year OS rate was 37.3%, with a median OS of 35.4 months.

CONCLUSIONS: This largest analysis of PAS to date demonstrates that most cases present as locoregional disease amenable to surgical resection, with favorable outcomes. The role of adjuvant therapy remains unclear, as no significant survival difference was observed between surgery alone and multimodal treatment.

PMID:39190497 | DOI:10.1002/jso.27836

Permalink for 'Influence of humanistic care-based operating room nursing on safety, recovery, and satisfaction after radical surgery for colorectal carcinoma'

Influence of humanistic care-based operating room nursing on safety, recovery, and satisfaction after radical surgery for colorectal carcinoma

Fetched: August 28th, 2024, 2:00am UTC by Xian-Pu Wang

World J Clin Cases. 2024 Aug 26;12(24):5483-5491. doi: 10.12998/wjcc.v12.i24.5483.

ABSTRACT

BACKGROUND: Radical surgery is a preferred treatment for colorectal carcinoma, wherein nursing intervention is essential for postoperative recovery and prevention of complications. Recently, the application of humanistic care in medical care has attracted attention. Humanistic care emphasizes comprehensive care, with importance attached to patients' physical needs as well as psychological and emotional support to provide more humane and personalized care services. However, no clinical reports have examined the use of humanistic care in patients undergoing radical surgery for colorectal carcinoma.

AIM: To investigate the influence of humanistic care-based operating room nursing on the safety, postoperative recovery, and nursing satisfaction of patients who have undergone radical surgery for colorectal carcinoma.

METHODS: In total, 120 patients with rectal cancer who underwent surgery in Zhongnan Hospital of Wuhan University between August 2023 and March 2024 were selected and grouped based on the nursing methods employed. Of these patients, 55 were treated with routine nursing intervention (control group) and 65 were provided humanistic care-based operating room nursing (research group). The patients' vital signs were recorded, including systolic/diastolic blood pressure (SBP/DBP) and heart beats per minute (BPM), as well as serum stress indices, including norepinephrine (NE), adrenal hormone (AD), and cortisol (Cor). Postoperative recovery and complications were also recorded. Patients' negative emotions, life hope, and nursing satisfaction were evaluated using the Self-rating Depression/Anxiety Scale (SDS/SAS), Herth Hope Index (HHI), and self-developed nursing satisfaction questionnaire, respectively.

RESULTS: During emergence from anesthesia, SBP, DBP, and BPM levels were found to be lower in the research group than those in the control group, also serum Cor, AD, and NE levels were lower. In addition, the research group had shorter operative, awakening, anal exhaust, first postoperative ambulation, drainage tube removal, intestinal recovery, and hospital times. The total complication rate and the SDS and SAS scores were lower in the research group than those in the control group. The HHI and nursing satisfaction scores were higher in the research group.

CONCLUSION: Humanistic care-based operating room nursing can mitigate physiological stress responses, reduce postoperative complications, promote postoperative recovery, relieve adverse psychological emotions, and enhance life hope and nursing satisfaction in patients undergoing radical surgery for colorectal carcinoma, which can be popularized in clinical practice.

PMID:39188612 | PMC:PMC11269985 | DOI:10.12998/wjcc.v12.i24.5483

Lynch syndrome screening in patients with young-onset extra-colorectal Lynch syndrome-associated cancers

Fetched: August 28th, 2024, 2:00am UTC by Atsushi Yamada

Int J Clin Oncol. 2024 Aug 26. doi: 10.1007/s10147-024-02609-w. Online ahead of print.

ABSTRACT

BACKGROUND: Lynch syndrome (LS) is a hereditary cancer syndrome caused by pathogenic germline variants in mismatch repair (MMR) genes, which predisposes to various types of cancers showing deficient MMR (dMMR). Identification of LS probands is crucial to reduce cancer-related deaths in affected families. Although universal screening is recommended for colorectal and endometrial cancers, and age-restricted screening is proposed as an alternative, LS screening covering a broader spectrum of cancer types is needed. In the current study, we elucidated the rate of dMMR tumors and evaluated the outcome of LS screening in young-onset extra-colorectal LS-associated cancers.

METHODS: Immunohistochemistry for MMR proteins were retrospectively performed in a total of 309 tissue samples of endometrial, non-mucinous ovarian, gastric, urothelial, pancreatic, biliary tract, and adrenal cancers in patients < 50 years of age. Clinicopathological information and the results of genetic testing were obtained from medical charts.

RESULTS: There were 24 dMMR tumors (7.8%) including 18 endometrial, three ovarian, two urothelial, and one gastric cancer. Co-occurrence of colorectal cancer and family history of LS-associated cancers was significantly enriched in patients with dMMR tumors. Among the 16 patients with dMMR tumors who were informed of the immunohistochemistry results, five with endometrial and one with urothelial cancer were diagnosed as LS with positive pathogenic variants in MMR genes.

CONCLUSIONS: We report the outcome of immunohistochemistry for MMR proteins performed in multiple types of young-onset extra-colorectal LS-associated cancers. Our study demonstrates the feasibility of a comprehensive LS screening program incorporating young-onset patients with various types of extra-colorectal LS-associated cancers.

PMID:39187737 | DOI:10.1007/s10147-024-02609-w

Effectiveness of Robot-assisted Adrenalectomy for a Giant Adrenal Hemangioma: A Case Report

Fetched: August 28th, 2024, 2:00am UTC by Nanaka Katsurayama

In Vivo. 2024 Sep-Oct;38(5):2545-2549. doi: 10.21873/invivo.13728.

ABSTRACT

BACKGROUND: Adrenal hemangiomas are extremely rare benign tumors that often need to be distinguished from malignancies. Adrenal tumors >4 cm in size are treated surgically because the possibility of malignancy cannot be ruled out. Traditionally, open surgery has been the mainstay of treatment; however, in recent years, robot-assisted surgery has been increasingly used for tumors of larger size and suspected malignancy. Here, we report a case of robot-assisted adrenalectomy for an 11 cm adrenal hemangioma.

CASE REPORT: A 62-year-old male with lateral abdominal pain was referred to our hospital for further examination and treatment. His medical history was significant for hypertension, diabetes, and dyslipidemia. Computed tomography revealed an 11 cm left adrenal tumor, and all endocrinological screening tests were negative. Because the possibility of malignancy could not be ruled out, a robot-assisted adrenalectomy was performed. The operation time was 129 min, and the estimated blood loss was 7 ml. Pathological findings revealed an adrenal hemangioma. The postoperative course was uneventful, and patient's condition subsequently improved postoperatively.

CONCLUSION: Robot-assisted adrenalectomy was performed for a giant adrenal hemangioma without any complications. Robotic surgery is useful for resecting adrenal hemangiomas even exceeding 11 cm in diameter.

PMID:39187351 | PMC:PMC11363784 | DOI:10.21873/invivo.13728

Patterns of Growth of Tumors in Li-Fraumeni Syndrome by Imaging: A Case Series

Fetched: August 27th, 2024, 2:00am UTC by Roxana Azma

J Pediatr Hematol Oncol. 2024 Aug 26. doi: 10.1097/MPH.0000000000002928. Online ahead of print.

ABSTRACT

Although tumors of Li-Fraumeni syndrome (LFS) have a premalignant or dormant phase that could be exploited by early imaging detection, this has been underevaluated in the literature. We present a case series of patients with LFS followed by imaging over time to highlight patterns of growth of tumors and hotspots of missed tumors in this population. Clinical and imaging features were available for 29 tumors of 24 carriers of a germline TP53 pathogenic variant, developed between 1999 and 2023 were retrospectively reviewed in a single tertiary pediatric center. Imaging characteristics of tumors were evaluated with MRI, CT, and radiographs. Local invasion, time interval for developing primary cancer, and/or recurrent disease and metastasis, and factors that delayed the tumor diagnosis were assessed. In patients with multiple tumors the median time intervals for development of first, second, and third primary cancers were 45.9, 79.8, and 28.1 months, respectively. Hotspots of missed tumors included superficial soft tissues, areas close to bones, on the scalp, in tissues around the adrenal region and in small hypodense lesions on brain CT. In conclusion, the pattern of growth of tumors is variable and erratic in LFS patients with some tumors presenting with a dormant pattern.

PMID:39185882 | DOI:10.1097/MPH.0000000000002928

Inhibin subunit beta B (INHBB): an emerging role in tumor progression

Fetched: August 27th, 2024, 2:00am UTC by Ying Liu

J Physiol Biochem. 2024 Aug 26. doi: 10.1007/s13105-024-01041-y. Online ahead of print.

ABSTRACT

The gene inhibin subunit beta B (INHBB) encodes the inhibin Î²B subunit, which is involved in forming protein members of the transforming growth factor-Î² (TGF-Î²) superfamily. The TGF-Î² superfamily is extensively involved in cell proliferation, differentiation, adhesion, movement, metabolism, communication, and death. Activins and inhibins, which belong to the TGF-Î² superfamily, were first discovered in ovarian follicular fluid. They were initially described as regulators of pituitary follicle-stimulating hormone (FSH) secretion both in vivo and in vitro. Later studies found that INHBB is expressed not only in reproductive organs such as the ovary, uterus, and testis but also in numerous other organs, including the brain, spinal cord, liver, kidneys, and adrenal glands. This wide distribution implies its involvement in the normal physiological functions of various organs; however, the mechanisms underlying these functions have not yet been fully elucidated. Recent studies suggest that INHBB plays a significant, yet complex role in tumorigenesis. It appears to have dual effects, promoting tumor progression in some contexts while inhibiting it in others, although these roles are not yet fully understood. In this paper, we review the different expression patterns, functions, and mechanisms of INHBB in normal and tumor tissues to illustrate the research prospects of INHBB in tumor progression.

PMID:39183219 | DOI:10.1007/s13105-024-01041-y

A retrospective study of 96 cases of adrenal metastases

Fetched: August 27th, 2024, 2:00am UTC by D Cai

Zhonghua Nei Ke Za Zhi. 2024 Sep 1;63(9):855-860. doi: 10.3760/cma.j.cn112138-20240125-00074.

ABSTRACT

Objective: To analyze the clinical characteristics, etiological composition, imaging features, and prognosis of adrenal metastases. Methods: This study is a retrospective case series that included 96 patients with pathologically confirmed adrenal metastases who were treated at West China Hospital, Sichuan University, from 2007 to 2017. Clinical features such as sex, age, tumor size, biochemical tests, imaging characteristics, postoperative pathology, treatment methods, and prognosis were collected and analyzed. The prognosis of patients and its influencing factors were analyzed by Kaplan-Meier survival curve and single-factor Cox risk proportional model. Results: Among the 96 included patients, 64 were male and 32 were female, with a median age of 60 years. There were 89 cases of unilateral adrenal metastases, five cases of bilateral metastases, and two cases with unspecified laterality. The median diameter of the metastases was 3.5 cmÃ—2.9 cm, with an average CT value of 31 HU. Thirty-four cases of adrenal hormones were evaluated, and no abnormality was found.The primary tumor sites were as follows: lung (n=36), kidney (n=19), liver (n=12), pancreas (n=7), rectum (n=3), stomach (n=2), and one case each of tumor in the esophagus, skin, thyroid, left maxillary muscle, breast, bladder, cervix, chest wall, and gastrointestinal tract. There were three cases with unknown primary tumors. The most common pathological type was lung adenocarcinoma (20.8%, 20/96), followed by hepatocellular carcinoma (9.4%, 9/96) and high-grade invasive urothelial carcinoma of the kidney (8.3%, 8/96). Thirty-nine cases were diagnosed concurrently with the primary tumor, while 37 cases were diagnosed after the primary tumor, with a median interval of 15 months (range: 2-144 months). There was no significant correlation between the death risk of adrenal metastatic tumor patients and gender, age, and the size of the metastatic tumor (all P>0.05). There were 4 patients with radiotherapy and chemotherapy alone, 19 patients with surgery alone, and 6 patients with combined radiotherapy and chemotherapy. The median overall survival was 1, 3, and 7 years, respectively. Conclusions: Adrenal metastases were mostly diagnosed at the same time as the primary tumor or within 15 months after the diagnosis of the primary tumor. Unilateral metastasis is common. The lungs are the most common primary lesion, followed by the kidney and liver. CT is the preferred method for the diagnosis of adrenal metastases, and the plain CT value is more than 30 HU. The overall prognosis of adrenal metastases is poor. The prognosis was better for patients who underwent surgery combined with radiotherapy and chemotherapy than those who received only surgery or radiotherapy and chemotherapy alone.

PMID:39183157 | DOI:10.3760/cma.j.cn112138-20240125-00074

The value of serum dehydroepiandrosterone sulfate in the functional evaluation of adrenal space-occupying lesions in adults

Fetched: August 27th, 2024, 2:00am UTC by X J Rao

Zhonghua Nei Ke Za Zhi. 2024 Sep 1;63(9):849-854. doi: 10.3760/cma.j.cn112138-20240201-00092.

ABSTRACT

Objective: To evaluate the function of serum dehydroepiandrosterone sulfate (DHEAS) in adult adrenal space-occupying lesions. Methods: In this cross-sectional study, 395 patients with adrenal space-occupying lesions who had their DHEAS levels measured were collected from the First Medical Center of Chinese PLA General Hospital from January 2010 to June 2021. They were divided into the adrenal Cushing syndrome (ACS) group (n=100) and non-ACS group (n=295). The former was divided into the cortisol-producing adrenal adenoma (CPA) group (n=67) and primary bilateral macronodular adrenal hyperplasia (PBMAH) group (n=33). Clinical data of each group were collected and compared among groups by independent samples t-test, chi-square test, and Mann-Whitney U test. Serum DHEAS ratio corrected for age and sex was further constructed to identify the receiver operating characteristic curve and the optimal tangent point value for different adrenal occupation. Results: Patients in the ACS group were younger (44.9Â±13.7 vs. 49.9Â±12.5, P=0.001); had a larger proportion of women (79/100 vs.139/295, P=0.001); and had higher cortisol levels [8âˆ¶00Am, 497.31 (343.52, 606.50) vs. 353.11 (267.50, 487.91) nmol/L, P<0.001] than those in the non-ACS group. The serum DHEAS level and ratio in the ACS group were significantly lower than those in the non-ACS group [0.50 (0.40, 1.21) vs. 2.68 (1.56, 4.32) Î¼mol/L, 1.00 (0.43, 1.68) vs. 3.17 (2.21, 4.54), both P<0.001]. When the serum DHEAS ratio cut-off point was 1.29, the sensitivity and specificity for differential diagnosis of ACS and non-ACS were 72.0% and 91.5% respectively. The ratio of DHEAS in the CPA group was lower [0.58 (0.27, 1.05) vs. 1.14 (1.04, 2.40), P<0.001] than that in the PBMAH group. When the serum DHEAS ratio cut-off point was 0.99, the sensitivity and specificity for differential diagnosis of CPA and PBMAH were 64.2% and 81.2% respectively. Conclusion: Corrected age-sex DHEAS ratio can assist in the functional assessment of adrenal space-occupying lesions.

PMID:39183156 | DOI:10.3760/cma.j.cn112138-20240201-00092

Gangliocytic paraganglioma: A case report

Fetched: August 27th, 2024, 2:00am UTC by Ãlvaro Valverde MÃ¡rquez

Endocrinol Diabetes Nutr (Engl Ed). 2024 Aug-Sep;71(7):317-320. doi: 10.1016/j.endien.2024.03.023. Epub 2024 Aug 1.

ABSTRACT

Paragangliomas (PGLs) are rare and encapsulated neuroendocrine tumors (NET), located in the adrenal gland or the extra-adrenal paraganglia. Extra-adrenal PGLs may develop a gangliocytic component with ganglion cells which are called gangliocytic paragangliomas (GPs). The most common location is the duodenum, and they appear with digestive symptoms or as an incidental finding. We described a 43 years old patient, with epigastric pain, nausea and vomiting. The CT-scan reveals a nodular image in the duodenum. An ultrasound-guided FNA was performed and the pathological report revealed neuroendocrine cell groups and neural tissue. Surgery was the chosen treatment. As the patient did not present lymphatic or pancreatic parenchyma invasion, radiotherapy (RT) was not administered. The management of GPs is not well established and multidisciplinary team approach is recommended to lead to therapeutic options. Surgical resection is still key in the treatment, and adjuvant RT may be considered in cases of lymph node invasion.

PMID:39089969 | DOI:10.1016/j.endien.2024.03.023

Permalink for 'Sunitinib for the treatment of patients with advanced pheochromocytomas or paragangliomas: The phase 2 non-randomized SUTNET clinical trial'

Sunitinib for the treatment of patients with advanced pheochromocytomas or paragangliomas: The phase 2 non-randomized SUTNET clinical trial

Fetched: August 25th, 2024, 2:00am UTC by Vincenzo Nasca

Eur J Cancer. 2024 Sep;209:114276. doi: 10.1016/j.ejca.2024.114276. Epub 2024 Aug 9.

ABSTRACT

BACKGROUND: Metastatic Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors characterized by high morbidity and limited systemic treatment options, mainly based on radiometabolic treatments or chemotherapy. Based on the preclinical rationale that PGGLs carcinogenesis relies on angiogenesis, treatment with tyrosine kinase inhibitors (TKI) may represent another viable therapeutic option.

METHODS: We conducted a prospective phase II study in patients with metastatic or unresectable PGGLs. Patients received sunitinib (50 mg daily for 4 weeks, followed by a 2-week rest period) until progressive disease (PD), unacceptable toxicity or consent withdrawal. The primary endpoint was 12-month progression-free survival (PFS) rate; secondary endpoints were safety overall response rate (ORR) according to RECIST 1.1 criteria and overall survival (OS). EudraCT Number: 2011-002632-99.

RESULTS: Fifty patients were included. At a median follow-up of 71.7 months (IQR 35.4-100.1), the 1 year-PFS rate was 53.4 % (95 %CI 41.1-69.3) and median PFS was 14.1 months (95 % CI 8.9-25.7). ORR was 15.6 %, the median OS was 49.4 months (95 %CI 21.2-NA), and grade 3 or higher treatment-related adverse events were reported in 34 % patients. No significant correlation was found between specific genetic alterations or genomic clusters and sunitinib efficacy.

CONCLUSION: Sunitinib is an active drug in patients with advanced PGGLs, capable of inducing prolonged disease control with a manageable toxicity profile.

PMID:39128186 | DOI:10.1016/j.ejca.2024.114276

Permalink for 'Acute onset of hypertensive encephalopathy in a dog with right adrenal pheochromocytoma and neoplastic invasion of the caudal vena cava: Case report and review of the literature'

Acute onset of hypertensive encephalopathy in a dog with right adrenal pheochromocytoma and neoplastic invasion of the caudal vena cava: Case report and review of the literature

Fetched: August 24th, 2024, 2:00am UTC by Alessandra Recchia

Open Vet J. 2024 Jul;14(7):1716-1725. doi: 10.5455/OVJ.2024.v14.i7.21. Epub 2024 Jul 31.

ABSTRACT

BACKGROUND: Canine pheochromocytomas (PCCs) are rare tumors of the adrenal medulla. Clinical signs are often vague, resulting in intermittent catecholamine over secretion or neoplastic invasion of adjacent structures.

CASE DESCRIPTION: A 12-year-old Epagneul Breton dog with a 1-year history of chronic kidney disease, was examined for acute onset of severe neurological signs. Based on clinical and instrumental data, hypertensive encephalopathy was suspected. Cardiac and abdominal ultrasound were performed. Severe hypertensive cardiopathy and a right adrenal gland mass with invasion of the caudal vena cava were diagnosed. Computed tomography imaging confirmed the suspect of invasive malignant neoplasia. Emergency pharmacological therapy was started to reduce systemic pressure, improve clinical signs, and stabilize the dog in view of surgical resolution. After initial improvement, patient conditions abruptly worsened, and euthanasia was elected. Histology examination confirmed a right adrenal PCC, with caval invasion.

CONCLUSION: To the authors' conclusions, acute hypertensive encephalopathy is a peculiar manifestation of PCCs. Ultrasound is a useful, and rapid test to suspect PCC as it can detect adrenal alterations, caval invasion, metastasis, and cardiac sequelae consistent with the condition. PCC can mimic multiple affections, and be misinterpreted, especially when a concurrent disease has already been diagnosed. Veterinarians need to be aware that comorbidities could mask clinical signs and delay diagnosis. Furthermore, this clinical case reminds us to include PCC also in the differential diagnosis of dogs with an acute onset of severe neurological signs.

PMID:39175984 | PMC:PMC11338619 | DOI:10.5455/OVJ.2024.v14.i7.21

PRAP study - Partial versus Radical Adrenalectomy in hereditary Pheochromocytomas

Fetched: August 23rd, 2024, 2:00am UTC by Kai Xu

Eur J Endocrinol. 2024 Aug 22:lvae108. doi: 10.1093/ejendo/lvae108. Online ahead of print.

ABSTRACT

OBJECTIVE: Hereditary pheochromocytoma (hPCC) commonly develops bilaterally, causing adrenal insufficiency when standard treatment, radical adrenalectomy (RA), is performed. Partial adrenalectomy (PA) aims to preserve adrenal function, but with higher recurrence rates. This study compares outcomes of PA versus RA in hPCC.

METHODS: Patients with hPCC due to pathogenic variants in RET, VHL, NF1, MAX, and TMEM127 from 12 European centers (1974-2023) were studied retrospectively. Stratified analysis based on surgery type and initial presentation was conducted. Main outcomes included recurrence, adrenal insufficiency, metastasis, and mortality.

RESULTS: The study included 256 patients (223 RA, 33 PA). Ipsilateral recurrence rates were 9/223 (4%) after RA versus 5/33 (15%) after PA (P=0.02). Metastasis and mortality did not differ between groups. Overall, 103 patients (40%) underwent bilateral adrenalectomy either synchronously or metachronously (75 RA, 28 PA). Of these, 46% developed adrenal insufficiency after PA.In total, 191 patients presented with initial unilateral disease, of whom 50 (26%) developed metachronous contralateral disease, most commonly in RET, VHL, and MAX. In patients with metachronous bilateral disease, adrenal insufficiency developed in 3/4 (75%) when PA was performed as first operation followed by RA, compared to 1/7 (14%) when PA was performed as second operation after prior RA (P=0.09).

CONCLUSION: In patients with hPCC undergoing PA, local recurrence rates are higher than after RA, but metastasis and disease-specific mortality are similar. Therefore, PA seems a safe method to preserve adrenal function in patients with hPCC, both in cases of synchronous and metachronous bilateral disease, when performed as second operation.

PMID:39171965 | DOI:10.1093/ejendo/lvae108

Permalink for 'Primary Unilateral Macronodular Adrenal Hyperplasia With Concomitant Glucocorticoid And Androgen Excess And KDM1A Inactivation'

Primary Unilateral Macronodular Adrenal Hyperplasia With Concomitant Glucocorticoid And Androgen Excess And KDM1A Inactivation

Fetched: August 23rd, 2024, 2:00am UTC by Yasir S Elhassan

Eur J Endocrinol. 2024 Aug 22:lvae106. doi: 10.1093/ejendo/lvae106. Online ahead of print.

ABSTRACT

BACKGROUND: Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause of Cushing's syndrome. Individuals with PBMAH and GIP-dependent Cushing's syndrome due to ectopic expression of the gastric inhibitory polypeptide receptor (GIPR) typically harbour inactivating KDM1A sequence variants. Primary unilateral macronodular adrenal hyperplasia (PUMAH) with concomitant glucocorticoid and androgen excess has never been encountered or studied.

METHODS: We investigated a woman with a large, heterogeneous adrenal mass and severe ACTH-independent glucocorticoid and androgen excess, a biochemical presentation typically suggestive of adrenocortical carcinoma. The patient presented during pregnancy (22nd week of gestation) and reported an 18-month history of oligomenorrhoea, hirsutism, and weight gain. We undertook an exploratory study with detailed histopathological and genetic analysis of the resected adrenal mass and leukocyte DNA collected from the patient and her parents.

RESULTS: Histopathology revealed benign macronodular adrenal hyperplasia. Imaging showed a persistently normal contralateral adrenal gland. Whole-exome sequencing of four representative nodules detected KDM1A germline variants, benign NM_001009999.3:c.136G>A:p.G46S and likely pathogenic NM_001009999.3:exon6:c.865_866del:p.R289Dfs*7. Copy number variation analysis demonstrated an additional somatic loss of the KDM1A wild-type allele on chromosome 1p36.12 in all nodules. RNA-sequencing of a representative nodule showed low/absent KDM1A expression and increased GIPR expression compared to 52 unilateral sporadic adenomas and four normal adrenal glands. LH Receptor (LHCGR) expression was normal. Sanger sequencing confirmed heterozygous KDM1A variants in both parents (father: p.R289Dfs*7; mother: p.G46S) who showed no clinical features suggestive of glucocorticoid or androgen excess.

CONCLUSIONS: We investigated the first PUMAH associated with severe Cushing's syndrome and concomitant androgen excess, suggesting pathogenic mechanisms involving KDM1A.

PMID:39171930 | DOI:10.1093/ejendo/lvae106

Hypopituitarism Following Cranial Radiotherapy

Fetched: August 22nd, 2024, 2:00am UTC by Sandra Pekic

2024 Aug 17. In: Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, de Herder WW, Dhatariya K, Dungan K, Hofland J, Kalra S, Kaltsas G, Kapoor N, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, LaferrÃ¨re B, Levy M, McGee EA, McLachlan R, New M, Purnell J, Sahay R, Shah AS, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000â€“.

ABSTRACT

Radiation treatment is used for patients with secreting and non-secreting pituitary adenomas, with residual pituitary adenomas, or recurrent pituitary adenomas with the aim to achieve long term disease control. Radiotherapy is an integral component of the management of other tumors in the sellar region (craniopharyngiomas) and for certain types of cancers and lymphomas. Pituitary hormone deficiencies are the commonest late complication of radiotherapy, which usually occurs after several years. The development of hormone deficiencies with time varies in the published literature. Predictors for the development of hypopituitarism are the dose of radiation and the age at time of treatment. Different pituitary axes appear to have different radio-sensitivity with the somatotrophic axis being the most sensitive. Long-term endocrine evaluations are recommended in patients after cranial radiotherapy to identify new pituitary hormone deficiencies and introduce appropriate hormone replacement therapy. Clinical evaluation, baseline pituitary hormone assessment, and dynamic testing for growth hormone and adrenocorticotropic hormone (ACTH) deficiency should begin one year after cranial radiotherapy. Compared with conventional radiotherapy, advanced radiation technologies (stereotactic radiosurgery, cyber knife, fractionated stereotactic radiotherapy, proton beam therapy) are presumed to have the ability to deliver radiation to the tumor with remarkable precision minimizing its effects on healthy tissues. Results from larger series with longer length of follow-up are needed to help clinicians identify who will benefit most from advanced radiation techniques. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:30321012 | Bookshelf:NBK532082

Permalink for 'Deleterious ZNRF3 germline variants cause neurodevelopmental disorders with mirror brain phenotypes via domain-specific effects on Wnt/Î²-catenin signaling'

Deleterious ZNRF3 germline variants cause neurodevelopmental disorders with mirror brain phenotypes via domain-specific effects on Wnt/Î²-catenin signaling

Fetched: August 22nd, 2024, 2:00am UTC by Paranchai Boonsawat

Am J Hum Genet. 2024 Aug 16:S0002-9297(24)00260-X. doi: 10.1016/j.ajhg.2024.07.016. Online ahead of print.

ABSTRACT

Zinc and RING finger 3 (ZNRF3) is a negative-feedback regulator of Wnt/Î²-catenin signaling, which plays an important role in human brain development. Although somatically frequently mutated in cancer, germline variants in ZNRF3 have not been established as causative for neurodevelopmental disorders (NDDs). We identified 12 individuals with ZNRF3 variants and various phenotypes via GeneMatcher/Decipher and evaluated genotype-phenotype correlation. We performed structural modeling and representative deleterious and control variants were assessed using in vitro transcriptional reporter assays with and without Wnt-ligand Wnt3a and/or Wnt-potentiator R-spondin (RSPO). Eight individuals harbored de novo missense variants and presented with NDD. We found missense variants associated with macrocephalic NDD to cluster in the RING ligase domain. Structural modeling predicted disruption of the ubiquitin ligase function likely compromising Wnt receptor turnover. Accordingly, the functional assays showed enhanced Wnt/Î²-catenin signaling for these variants in a dominant negative manner. Contrarily, an individual with microcephalic NDD harbored a missense variant in the RSPO-binding domain predicted to disrupt binding affinity to RSPO and showed attenuated Wnt/Î²-catenin signaling in the same assays. Additionally, four individuals harbored de novo truncating or de novo or inherited large in-frame deletion variants with non-NDD phenotypes, including heart, adrenal, or nephrotic problems. In contrast to NDD-associated missense variants, the effects on Wnt/Î²-catenin signaling were comparable between the truncating variant and the empty vector and between benign variants and the wild type. In summary, we provide evidence for mirror brain size phenotypes caused by distinct pathomechanisms in Wnt/Î²-catenin signaling through protein domain-specific deleterious ZNRF3 germline missense variants.

PMID:39168120 | DOI:10.1016/j.ajhg.2024.07.016

Permalink for 'HSD3B1 genotype and outcomes in metastatic hormone-sensitive prostate cancer with androgen deprivation therapy and enzalutamide: ARCHES'

HSD3B1 genotype and outcomes in metastatic hormone-sensitive prostate cancer with androgen deprivation therapy and enzalutamide: ARCHES

Fetched: August 22nd, 2024, 2:00am UTC by Nima Sharifi

Cell Rep Med. 2024 Aug 20;5(8):101644. doi: 10.1016/j.xcrm.2024.101644.

ABSTRACT

HSD3B1 encodes 3Î²-hydroxysteroid dehydrogenase-1, which converts adrenal dehydroepiandrosterone to 5Î±-dihydrotestosterone and is inherited in adrenal-permissive (AP) or adrenal-restrictive forms. The AP allele is linked to castration resistance, mainly in low-volume tumors. Here, we investigate the association of HSD3B1 alleles with outcomes in ARCHES, a multinational, double-blind, randomized, placebo-controlled phase 3 trial that demonstrated clinical benefit with enzalutamide plus androgen deprivation therapy (ADT) in men with metastatic hormone-sensitive prostate cancer (mHSPC) compared to those treated with placebo plus ADT. There are no significant differences between genotypes for clinical efficacy endpoints. Enzalutamide significantly improves radiographic progression-free survival and overall survival vs. placebo irrespective of HSD3B1 status. Men with the AP genotype have higher post-progression mortality and treatment-emergent adverse events, including hypertension, cardiovascular events, and gynecomastia, but a lower fracture rate. Overall, enzalutamide is beneficial in men with mHSPC independent of the HSD3B1 genotype. Inherited polymorphisms of HSD3B1 may account for differential toxicities.

PMID:39168093 | DOI:10.1016/j.xcrm.2024.101644

Permalink for 'Dielectric characterisation of human adrenal glands and adrenal tumours for the development of microwave ablation technologies for hypertension treatment'

Dielectric characterisation of human adrenal glands and adrenal tumours for the development of microwave ablation technologies for hypertension treatment

Fetched: August 22nd, 2024, 2:00am UTC by Bilal Amin

Sci Rep. 2024 Aug 21;14(1):19451. doi: 10.1038/s41598-024-70476-6.

ABSTRACT

Adrenal gland-induced hypertension results from underlying adrenal gland disorders including Conn's syndrome, Cushing's syndrome, and Pheochromocytoma. These adrenal disorders are a risk for cardiovascular and renal morbidity and mortality. Clinically, treatment for adrenal gland-induced hypertension involves a pharmaceutical or surgical approach. The former presents very significant side effects whereas the latter can be ineffective in cases where the adrenal disorder reoccurs in the remaining contralateral adrenal gland. Due to the limitations of existing treatment methods, minimally invasive treatment options like microwave ablation (MWA) have received significant attention for treating adrenal gland disorders. A precise comprehension of the dielectric properties of human adrenal glands will help to tailor energy delivery for MWA therapy, thus offering the potential to optimise treatments and minimise damage to surrounding tissues. This study reports the ex vivo dielectric properties of human adrenal glands, including the cortex, medulla, capsule, and tumours, based on the data obtained from four patients (diagnosed with Conn's syndrome, Cushing's syndrome, and Pheochromocytoma) who underwent unilateral adrenalectomy at the University Hospital Galway, Ireland. An open-ended coaxial probe measurement technique was used to measure the dielectric properties for a frequency range of 0.5-8.5 GHz. The dielectric properties were fitted using a two-pole Debye model, and a weighted least squares method was employed to optimise the model parameters. Moreover, the dielectric properties of adrenal tissues and tumours were compared across frequencies commonly used in MWA, including 915 MHz, 2.45 GHz, and 5.8 GHz. The study found that the dielectric properties of adrenal tumours were influenced by the presence of lipid-rich adenomas, and the dielectric properties of Cushing's syndrome tumour were lowest in comparison to the tumours in patients diagnosed with Conn's syndrome and Pheochromocytoma. Furthermore, a notable difference was observed in the dielectric properties of the medulla and cortex among patients diagnosed with Conn's syndrome, Cushing's syndrome, and Pheochromocytoma. These findings have significant implications for the diagnosis and treatment of adrenal tumours, including the optimisation of MWA therapy for precise ablation of adrenal masses.

PMID:39169260 | PMC:PMC11339330 | DOI:10.1038/s41598-024-70476-6

Single-nucleus and spatial transcriptome reveal adrenal homeostasis in normal and tumoural adrenal glands

Fetched: August 22nd, 2024, 2:00am UTC by Barbara Altieri

Clin Transl Med. 2024 Aug;14(8):e1798. doi: 10.1002/ctm2.1798.

ABSTRACT

The human adrenal gland is a complex endocrine tissue. Studies on adrenal renewal have been limited to animal models or human foetuses. Enhancing our understanding of adult human adrenal homeostasis is crucial for gaining insights into the pathogenesis of adrenal diseases, such as adrenocortical tumours. Here, we present a comprehensive cellular genomics analysis of the adult human normal adrenal gland, combining single-nuclei RNA sequencing and spatial transcriptome data to reconstruct adrenal gland homeostasis. As expected, we identified primary cells of the various zones of the adrenal cortex and medulla, but we also uncovered additional cell types. They constitute the adrenal microenvironment, including immune cells, mostly composed of a large population of M2 macrophages, and new cell populations, including different subpopulations of vascular-endothelial cells and cortical-neuroendocrine cells. Utilizing spatial transcriptome and pseudotime trajectory analysis, we support evidence of the centripetal dynamics of adrenocortical cell maintenance and the essential role played by Wnt/Î²-catenin, sonic hedgehog, and fibroblast growth factor pathways in the adult adrenocortical homeostasis. Furthermore, we compared single-nuclei transcriptional profiles obtained from six healthy adrenal glands and twelve adrenocortical adenomas. This analysis unveiled a notable heterogeneity in cell populations within the adenoma samples. In addition, we identified six distinct adenoma-specific clusters, each with varying distributions based on steroid profiles and tumour mutational status. Overall, our results provide novel insights into adrenal homeostasis and molecular mechanisms potentially underlying early adrenocortical tumorigenesis and/or autonomous steroid secretion. Our cell atlas represents a powerful resource to investigate other adrenal-related pathologies.

PMID:39167619 | PMC:PMC11338279 | DOI:10.1002/ctm2.1798

Solitary Osseous Metastasis of Hepatocellular Carcinoma on SPECT/CT

Fetched: August 21st, 2024, 2:00am UTC by Sana Munir Gill

J Pak Med Assoc. 2024 Aug;74(8):1555-1556. doi: 10.47391/JPMA.24-65.

ABSTRACT

Hepatocellular carcinoma (HCC), sixth most common cancer world-over, commonly metastasizes to lung, lymph nodes and adrenal glands. Incidence of osseous metastases in HCC has been reported to be 3-20 % which occurs predominantly in the axial skeleton. It only rarely occurs in the appendicular skeleton and that too as the solitary focus of metastatic deposit.3,4 We present a case of HCC with solitary osseous metastases to the proximal tibia.

PMID:39160737 | DOI:10.47391/JPMA.24-65

A real-world drug safety surveillance study of lenvatinib from the FAERS database

Fetched: August 16th, 2024, 2:00am UTC by Yipin Yang

Expert Opin Drug Saf. 2024 Aug 21:1-13. doi: 10.1080/14740338.2024.2393284. Online ahead of print.

ABSTRACT

BACKGROUND: There is a need to determine lenvatinib-associated real-world adverse events (AEs) as its adverse effects may result in its discontinuation.

RESEARCH DESIGN AND METHODS: Lenvatinib-associated AEs were analyzed and quantified and risk signals from the first quarter of 2015 to the fourth quarter of 2023 were detected through data mining. Potential targets for lenvatinib-associated cholecystitis, cholangitis, and hepatic encephalopathy were identified by data mining.

RESULT: 68 Preferred Terms (PTs) with an important imbalance were kept. Unexpected AEs, such as immune-mediated hepatitis, portal vein thrombosis and adrenal insufficiency were associated with the use of lenvatinib use. Lenvatinib alone was more strongly associated with adrenal insufficiency than lenvatinib and pembrolizumab combination. Hepatic encephalopathy was more strongly correlated with drug use when Lenvatinib was administered to male patients with hepatocellular carcinoma. Most AEs occurred during the first month after treatment, with a median onset time of 41 days. FGFR4, PDGFRA, and KIT (Lenvatinib targets) are potentially linked to cholecystitis, cholangitis, and hepatic encephalopathy.

CONCLUSIONS: We identified Lenvatinib-associated AEs and discovered new AEs that will be useful for clinical monitoring and risk assessment.

PMID:39145923 | DOI:10.1080/14740338.2024.2393284

Permalink for 'Abscopal effect in a patient with advanced hepatocellular carcinoma upon resuming bevacizumab in combination with atezolizumab after radiotherapy'

Abscopal effect in a patient with advanced hepatocellular carcinoma upon resuming bevacizumab in combination with atezolizumab after radiotherapy

Fetched: August 15th, 2024, 2:00am UTC by Tasuku Nakabori

Clin J Gastroenterol. 2024 Aug 14. doi: 10.1007/s12328-024-02030-w. Online ahead of print.

ABSTRACT

Combining bevacizumab with atezolizumab enhances the antitumor effects of the treatment by activating an immune response. This combination is approved for the treatment of unresectable hepatocellular carcinoma (HCC). An abscopal effect is associated with an immune response triggered by radiation-induced immunogenic cell death, based on experimental models. Thus, combining radiotherapy and immunotherapy is expected to induce an abscopal effect. However, the clinical significance of immunotherapy in the abscopal effect remains unknown due to the rarity of clinical cases. Herein, we report a case of advanced HCC with lung and adrenal metastases. The antitumor efficacy of atezolizumab and bevacizumab (atezo/bev) was enhanced following stereotactic body radiotherapy (SBRT), although atezo/bev did not yield a sufficient therapeutic response pre-SBRT. Furthermore, an abscopal effect following SBRT was not observed during atezolizumab alone but was evoked after resuming bevacizumab in combination with atezolizumab, culminating in the patient achieving a complete response status. These findings suggest that immune activation following radiotherapy may be related to the induction of an abscopal effect in clinical practice as well as in experimental settings, and combining immunotherapy with bevacizumab post-radiotherapy could evoke an abscopal effect in a case of HCC, even though immune checkpoint inhibitor use alone may be insufficient.

PMID:39141191 | DOI:10.1007/s12328-024-02030-w

Characteristics of Adrenal Hemorrhage: A Single Clinic's Experience

Fetched: August 15th, 2024, 2:00am UTC by Siavash Åšwieczkowski-Feiz

Pol Przegl Chir. 2024 Apr 2;96(4):36-43. doi: 10.5604/01.3001.0054.4570.

ABSTRACT

Introduction: Adrenal hemorrhage (AH) is a very rare and potentially life-threatening disease which may be secondary to trauma or of non-traumatic etiology.Aim: The aim of the study was to present the characteristics and management of adrenal hemorrhage and show that adrenal hemorrhage is more common than expected and that the clinical symptoms are not specific.Materials and methods: This retrospective study involved 199 patients with postoperative diagnosis of adrenal hemorrhage.Discussion: The factors identified as potential causes of adrenal hemorrhage are adrenocortical carcinoma, pheochromocytoma, and adrenal adenoma. The study group included 199 patients with postoperative diagnosis of AH. It showed that all patients with postoperative diagnosis had pheochromocytoma (n = 54), adrenal adenoma (n = 68), or adenocarcinoma (n = 17). If we look more careful at the results, we can find only 30% of patients (n = 39) with preoperative diagnosis of AH. This group of 39 patients was prepared for expedited surgery. In this group of patients, the preoperative diagnosis of AH was pheochromocytoma 28% (n = 11), adenocarcinoma (n = 4), and adrenal adenoma (n = 9).Conclusions: Bleeding into adrenal tumors is still an insufficiently understood topic due to its unpredictability and, as can be seen in our material, of varying severity. Out of 199 patients, only 30% (n = 39) were prepared for surgery with a preoperative diagnosis of AH; most of them had pheochromocytoma. We suggest that is very important to prepare patients for surgery with a preoperative diagnosis of AH using Î±-adrenoreceptor antagonists. Prolongation of the diagnostic process (time between the imaging examination and the surgery) may result in the disease progressing and adrenal bleeding.

PMID:39138988 | DOI:10.5604/01.3001.0054.4570

Permalink for 'Surface functionalized nanomaterial systems for targeted therapy of endocrine related tumors: a review of recent advancements'

Surface functionalized nanomaterial systems for targeted therapy of endocrine related tumors: a review of recent advancements

Fetched: August 14th, 2024, 2:00am UTC by Limei Liu

Drug Deliv. 2024 Dec;31(1):2390022. doi: 10.1080/10717544.2024.2390022. Epub 2024 Aug 13.

ABSTRACT

The application of multidisciplinary techniques in the management of endocrine-related cancers is crucial for harnessing the advantages of multiple disciplines and their coordinated efforts in eliminating tumors. Due to the malignant characteristics of cancer cells, they possess the capacity to develop resistance to traditional treatments such as chemotherapy and radiotherapy. Nevertheless, despite diligent endeavors to enhance the prediction of outcomes, the overall survival rate for individuals afflicted with endocrine-related malignancy remains quite miserable. Hence, it is imperative to investigate innovative therapy strategies. The latest advancements in therapeutic tactics have offered novel approaches for the therapy of various endocrine tumors. This paper examines the advancements in nano-drug delivery techniques and the utilization of nanomaterials for precise cancer cures through targeted therapy. This review provides a thorough analysis of the potential of combined drug delivery strategies in the treatment of thyroid cancer, adrenal gland tumors, and pancreatic cancer. The objective of this study is to gain a deeper understanding of current therapeutic approaches, stimulate the development of new drug DDS, and improve the effectiveness of treatment for patients with these diseases. The intracellular uptake of pharmaceuticals into cancer cells can be significantly improved through the implantation of synthetic or natural substances into nanoparticles, resulting in a substantial reduction in the development of endocrine malignancies.

PMID:39138394 | PMC:PMC11328606 | DOI:10.1080/10717544.2024.2390022

ADRENOCORTICAL CARCINOMA: AN ORPHAN MALIGNANCY: FROM THE PATIENT TO THE BENCH AND BACK

Fetched: August 14th, 2024, 2:00am UTC by Margaret E Wierman

Trans Am Clin Climatol Assoc. 2024;134:113-122.

ABSTRACT

Adrenocortical carcinoma (ACC) is an orphan cancer with 35% five-year survival that has been unchanged for last five decades. Patients often present with severe hypercortisolism or with mass effects. The only Food and Drug Administration (FDA)-approved drug for ACC is mitotane, an insecticide derivative, which provides only limited additional months of survival, but with toxicities. Little progress in the field has occurred due to a lack of preclinical models. We recently developed new human ACC in vitro and in vivo research models. We produced the first two new ACC cell lines for the field, CU-ACC1 and CU-ACC2, which we have distributed for global collaborations. In addition, we developed 10 ACC patient-derived xenograft (PDX) and two humanized ACC-PDX models to test new therapeutics and examine the mechanism of mitotane action in combination with immunotherapy. These new preclinical models allow us to identify novel targets and test new therapeutics for our patients with adrenal cancer.

PMID:39135585 | PMC:PMC11316896

Permalink for 'Development and validation of a liquid chromatography coupled to a diode array detector (LC-DAD) method for measuring mitotane (DDD) in plasma samples'

Development and validation of a liquid chromatography coupled to a diode array detector (LC-DAD) method for measuring mitotane (DDD) in plasma samples

Fetched: August 14th, 2024, 2:00am UTC by Anna Sylvia Ferrari Marques

Clinics (Sao Paulo). 2024 Aug 10;79:100470. doi: 10.1016/j.clinsp.2024.100470. eCollection 2024.

ABSTRACT

INTRODUCTION: Mitotane (o,p'-DDD) is the drug of choice for Adrenocortical Carcinomas (ACC) and its measurement in plasma is essential to control drug administration.

OBJECTIVE: To develop and validate a simple, reliable and straightforward method for mitotane determination in plasma samples.

METHOD: Drug-free plasma samples were collected in potassium-ethylenediamine tetraacetate (K-EDTA) tubes and spiked with 1.0, 2.5, 10.0, 25.0 and 50.0 Âµg/mL of mitotane (DDD). The p,p'-DDD was used as an Internal Standard (IS) and was added at 25.0 Âµg/mL concentration to all samples, standards and controls. Samples were submitted to protein precipitation with acetonitrile and then centrifuged. 50 uL of the supernatant was injected into an HPLC system coupled to a Diode Array Detector (DAD). DDD and IS were detected at 230 nm in a 12 min isocratic mode with a solvent mixture of 60 % acetonitrile and 40 % formic acid in water with 0.1 % pump mixed, at 0.6 mL/min flow rate, in a reversed-phase (C18) chromatographic column kept at 28Â°C. The sensitivity, selectivity, precision, presence of carry-over, recovery and matrix-effect, linearity, and method accuracy were evaluated.

RESULTS: The present study's method resulted in a symmetrical peak shape and good baseline resolution for DDD (mitotane) and 4,4'-DDD (internal standard) with retention times of 6.0 min, 6.4 mim, respectively, with resolutions higher than 1.0. Endogenous plasma compounds did not interfere with the evaluated peaks when blank plasma and spiked plasma with standards were compared. Linearity was assessed over the range of 1.00-50.00 Âµg/mL for mitotane (R2 > 0.9987 and a 97.80 %â€’105.50 % of extraction efficiency). Analytical sensitivity was 0.98 Âµg/mL. Functional sensitivity (LOQ) was 1.00 Âµg/L, intra-assay and inter-assay coefficient of variations were less than 9.98 %, and carry-over was not observed for this method. Recovery ranged from 98.00 % to 117.00 %, linearity ranged from 95.00 % to 119.00 %, and high accuracy of 89.40 % to 105.90 % with no matrix effects or interference was observed for mitotane measurements. Patients' sample results were compared with previous measurements by the GC-MS method with a high correlation (r = 0.88 and bias = -10.20 %).

CONCLUSION: DDD determination in plasma samples by the developed and validated method is simple, robust, efficient, and sensitive for therapeutic drug monitoring and dose management to achieve a therapeutic index of mitotane in patients with adrenocortical cancer.

PMID:39128398 | PMC:PMC11366885 | DOI:10.1016/j.clinsp.2024.100470

Permalink for 'Development and validation of a model predicting adrenal lipid-poor adenoma based on the minimum attenuation value from non-contrast CT: a dual-center retrospective study'

Development and validation of a model predicting adrenal lipid-poor adenoma based on the minimum attenuation value from non-contrast CT: a dual-center retrospective study

Fetched: August 13th, 2024, 2:00am UTC by Hanlin Zhu

BMC Med Imaging. 2024 Aug 12;24(1):210. doi: 10.1186/s12880-024-01392-4.

ABSTRACT

OBJECTIVE: The early differentiation of adrenal lipid-poor adenomas from non-adenomas is a crucial step in reducing excessive examinations and treatments. This study seeks to construct an eXtreme Gradient Boosting (XGBoost) predictive model utilizing the minimum attenuation values (minAVs) from non-contrast CT (NCCT) scans to identify lipid-poor adenomas.

MATERIALS AND METHODS: Retrospective analysis encompassed clinical data, minAVs, CT histogram (CTh), mean attenuation values (meanAVs), and lesion diameter from patients with pathologically or clinically confirmed adrenal lipid-poor adenomas across two medical institutions, juxtaposed with non-adenomas. Variable selection transpired in Institution A (training set), with XGBoost models established based on minAVs and CTh separately. Institution B (validation set) corroborated the diagnostic efficacy of the two models. Receiver operator characteristic (ROC) curve analysis, calibration curves, and Brier scores assessed the diagnostic performance and calibration of the models, with the Delong test gauging differences in the area under the curve (AUC) between models. SHapley Additive exPlanations (SHAP) values elucidated and visualized the models.

RESULTS: The training set comprised 136 adrenal lipid-poor adenomas and 126 non-adenomas, while the validation set included 46 and 40 instances, respectively. In the training set, there were substantial inter-group differences in minAVs, CTh, meanAVs, diameter, and body mass index (BMI) (p < 0.05 for all). The AUC for the minAV and CTh models were 0.912 (95% confidence interval [CI]: 0.866-0.957) and 0.916 (95% CI: 0.873-0.958), respectively. Both models exhibited good calibration, with Brier scores of 0.141 and 0.136. In the validation set, the AUCs were 0.871 (95% CI: 0.792-0.951) and 0.878 (95% CI: 0.794-0.962), with Brier scores of 0.156 and 0.165, respectively. The Delong test revealed no statistically significant differences in AUC between the models (p > 0.05 for both). SHAP value analysis for the minAV model suggested that minAVs had the highest absolute weight (AW) and negative contribution.

CONCLUSION: The XGBoost predictive model based on minAVs demonstrates effective discrimination between adrenal lipid-poor adenomas and non-adenomas. The minAV variable is easily obtainable, and its diagnostic performance is comparable to that of the CTh model. This provides a basis for patient diagnosis and treatment plan selection.

PMID:39134939 | PMC:PMC11318272 | DOI:10.1186/s12880-024-01392-4

Permalink for 'Expression of Survivin, CK7, ASH1, HMGB3, L587S, and CLCA2 in Peripheral Blood of Lung Cancer Patients by Real-Time Polymerase Chain Reaction'

Expression of Survivin, CK7, ASH1, HMGB3, L587S, and CLCA2 in Peripheral Blood of Lung Cancer Patients by Real-Time Polymerase Chain Reaction

Fetched: August 13th, 2024, 2:00am UTC by Sweety Gupta

Cureus. 2024 Jul 12;16(7):e64386. doi: 10.7759/cureus.64386. eCollection 2024 Jul.

ABSTRACT

Introduction The objective of the present study was to identify gene expression in peripheral blood by a real-time polymerase chain reaction (PCR) technique in patients who have lung carcinoma. Material and methods Peripheral blood samples of patients with non-small cell and small cell lung cancer were collected. Target genes included survivin, CK7, ASH1, HMGB3, L587S, and CLCA2. Î²-Actin was the reference gene. If the mean CT (threshold cycle) value for a target gene is â‰¥40, the gene expression is considered undetectable. Results Fifty patients with lung carcinoma were included and 30 healthy controls. Out of the six genes, survivin showed 26.8 times fold change as compared to controls; ASH1 and L587S were 0.54 and 0.06, respectively; and HMGB3, CLCA2, and CK7 had non-significant fold change in comparison to controls. The overall detection rate of the six target genes examined in lung cancer was 84%, with 42 out of 50 patients testing positive. Higher stages and ASH1 (p = 0.031), CK7 (p = <0.001), and HMGB3, p = 0.011 were associated significantly. CLCA2 had higher expression in patients without adrenal metastases (p = 0.044). Conclusions Lifestyle and geographical variation might be a probable cause of variable gene expression as compared to other studies. However, further research is needed to determine the clinical implication of these markers, especially in larger groups of early-stage patients.

PMID:39130876 | PMC:PMC11317019 | DOI:10.7759/cureus.64386

Permalink for 'From Nonfunctioning Adrenocortical Cancer to Biochemically Silent Paraganglioma Associated with SDHB Mutation: An Uncommon Presentation of a Patient with a Retroperitoneal Mass'

From Nonfunctioning Adrenocortical Cancer to Biochemically Silent Paraganglioma Associated with SDHB Mutation: An Uncommon Presentation of a Patient with a Retroperitoneal Mass

Fetched: August 13th, 2024, 2:00am UTC by Izabella Freitas

Case Rep Endocrinol. 2024 Aug 2;2024:6664694. doi: 10.1155/2024/6664694. eCollection 2024.

ABSTRACT

The combination of clinical characteristics and diagnostic exams including imaging, laboratory, and molecular tests help in the differential diagnosis of retroperitoneal lesions. We report a 41-year-old male with a metastatic retroperitoneal lesion with atypical characteristics, displaying pathological findings consistent with both nonsecretory pheochromocytomas/paragangliomas and adrenal cortex carcinoma. The patient was examined for abdominal pain, weight loss, and hypertension. Abdominal computed tomography showed a 21 Ã— 8 Ã— 10-cm right retroperitoneal mass. He was initially diagnosed as pheochromocytoma/paraganglioma (PHEO/PGL). However, the diagnosis was later changed to adrenocortical carcinoma based on histopathological features of the metastatic lesions and the findings of normal urinary levels of catecholamines/metanephrines. Systemic chemotherapy and abdominal radiotherapy were performed, in addition to multiple surgical resections, with no satisfactory response. The indolent course of the disease and minimal impact on the patient's performance status led to a genetic evaluation which resulted in the identification of a germline mutation in the succinate dehydrogenase complex subunit B (SDHB). An immunohistology review of previous slides was consistent with the hypothesis of a neuroendocrine tumor. Forty percent of the patients with PHEO/PGL have an underlying germline mutation. SDHB mutation is frequently associated with metastatic disease and dominant secretion of noradrenaline and/or dopamine. In addition to the metastatic disease, few cases with the mutations can be a biochemically silent PHEO/PGL. We concluded that the patient presented a metastatic abdominal paraganglioma associated with an SDHB mutation and we reinforced the need to perform genetic screening for all adrenal/extra-adrenal lesions characteristic of PHEO/PGL.

PMID:39129823 | PMC:PMC11315972 | DOI:10.1155/2024/6664694

A rare association of pheochromocytoma, paraganglioma, and pituitary adenoma (3PA): A case report and literature review

Fetched: August 10th, 2024, 2:00am UTC by Rahem Rahmati

Medicine (Baltimore). 2024 Aug 9;103(32):e38928. doi: 10.1097/MD.0000000000038928.

ABSTRACT

RATIONALE: 3P association (3PA) is a rare condition with co-occurrence of pituitary adenoma and pheochromocytoma/paraganglioma. There have been less than a hundred documented cases of 3PA, which can be sporadic or related to genetic mutations. The present case report describes the first Iranian patient with 3PA and a 90th case of 3PA in the available literature.

PATIENT CONCERNS AND INTERVENTIONS: A 36-year-old Caucasian male was admitted with headache and sudden increase in blood pressure. An abdominal CT scan revealed a retroperitoneal mass posterior to the inferior vena cava, later removed and diagnosed as a pheochromocytoma. Four years later, he noticed occasional mild headaches and a painless mass on the right side of his neck. The ultrasonography evaluations suggested a carotid body tumor, which was surgically removed. About a month after his second surgery, the severity of the patient's headaches worsened, and he developed right homonymous hemianopia. A brain MRI showed a mass in favor of macroadenoma, craniopharyngioma, or meningioma, and elevated prolactin level led to the diagnosis of macroprolactinoma.

DIAGNOSES: Based on the provided history, this patient was diagnosed with 3PA, and a genetic study identified a positive succinate-dehydrogenase-complex subunit b mutation, possibly linked to his family history of carotid body tumor.

OUTCOMES: He has remained symptom-free during his visits every 3 months.

LESSONS: The number of cases diagnosed with 3PA worldwide is increasing. Using clinical and genetic assessments, we can timely diagnose and adequately monitor individuals with or at risk of 3PA.

PMID:39121253 | PMC:PMC11315567 | DOI:10.1097/MD.0000000000038928

A Rare Case of Metastatic Adrenal Melanoma

Fetched: August 10th, 2024, 2:00am UTC by Rohma R Khan

Cureus. 2024 Jul 9;16(7):e64182. doi: 10.7759/cureus.64182. eCollection 2024 Jul.

ABSTRACT

Metastatic melanoma presents a significant clinical challenge, characterized by its aggressive nature and propensity to spread to multiple organ systems. Despite advances in detection and treatment, managing metastatic disease remains complex. Here, we present the case of a 43-year-old male with metastatic melanoma displaying an unusual pattern of involvement, affecting the adrenal gland, liver, spleen, and bones. The diagnostic process was intricate, involving atypical hormonal profiles and a negative BRAF status, necessitating a comprehensive approach for accurate characterization and treatment selection. Immunotherapy demonstrated efficacy but also highlighted the emergence of immune-related adverse events, notably hyperglycemia. This case discusses the heterogeneous nature of metastatic melanoma and underscores the importance of a multidisciplinary approach, close monitoring, and consideration of evolving treatment strategies in its management.

PMID:39119371 | PMC:PMC11309760 | DOI:10.7759/cureus.64182

Bowel Obstruction as the Initial Presentation of Urothelial Carcinoma

Fetched: August 9th, 2024, 2:00am UTC by Francisco GirÃ£o de Caires

Cureus. 2024 Jul 8;16(7):e64056. doi: 10.7759/cureus.64056. eCollection 2024 Jul.

ABSTRACT

Bowel obstructions are one of the main causes of hospital admissions for acute abdominal pain. In addition, bladder cancer is one of the most common cancers in the world. This said, bowel obstruction and bladder cancer are very frequent diseases but the same cannot be said about the association between these two pathologies. We report a unique case of an 80-year-old patient admitted to the emergency room with a bowel obstruction caused by a urothelial carcinoma with adrenal metastasis. The patient underwent an urgent laparotomy, and intraoperative inspection of the peritoneal cavity confirmed a large tumorous mass suspected of gastrointestinal etiology. The mass infiltrated the ileum and sigmoid colon and was apparently in contact with the bladder wall. An en-bloc resection of the lesion was performed. An R0 excison was not possible and fragments of the lesion were excised from the bladder wall for separate analysis. Histopathological examination of the resected specimen described a high-grade, undifferentiated urothelial carcinoma that originated in the bladder and invaded the ileum and sigmoid colon. The presence of an invasive urothelial carcinoma presenting with bowel obstruction represents an unexpected diagnosis and, although rare, the surgeon must be aware of this possibility. This case should serve as a reminder that a broad differential diagnosis should be considered when investigating an abdominal tumor.

PMID:39114229 | PMC:PMC11304121 | DOI:10.7759/cureus.64056

The Clinicopathological Characteristics and Prognosis of 55 Patients With TFE3-Rearranged Renal Cell Carcinomas

Fetched: August 8th, 2024, 2:00am UTC by Yin-Miao Bai

Clin Genitourin Cancer. 2024 Jul 16;22(5):102165. doi: 10.1016/j.clgc.2024.102165. Online ahead of print.

ABSTRACT

OBJECTIVE: To explore the clinicopathological features and prognosis of TFE3-rearranged renal cell carcinomas (TFE3-rRCC).

METHODS: In this retrospective observational study, the data of patients with TFE3-rRCC admitted to Xijing Hospital from January 2010 to October 2023 were collected, encompassing the general information, pathological diagnosis, immunohistochemistry, and the results of FISH detection. The treatment information and survival data of the patients were recorded during the follow-up.

RESULTS: A total of 55 patients with TFE3-rRCC were enrolled, among whom 25 were males and 30 were females. TFE3 FISH assay suggested the disruption of the TFE3 gene. Fifty-four patients underwent surgical resection of kidney lesions, while 1 patient did not. By the end of follow-up in December 2023, 3 patients were lost to follow-up, 28 patients remained alive, and 24 patients had died. Among the 52 patients followed up, 31 developed metastases, involving lymph nodes, liver, bone, lung, peritoneum, pleura, adrenal gland, and brain. The 1-year and 5-year survival rates of the patients were 84.6% and 50.6%, respectively. In this study, there were 31 patients with TFE3-rRCC recurrence or metastasis. Median PFS was 7 and 13 months in the VEGFR-TKI and VEGFR-TKI+ ICI groups, respectively. The median OS was 12 months in the VEGFR-TKI treatment group. The median OS data of VEGFR-TKI+ ICI group has not been reached. The ORR and DCR was 25%, 66.7% in the VEGFR-TKI group. The ORR and DCR was 33.3%, 77.8% in the VEGFR-TKI+ ICI group.

CONCLUSION: TFE3-rRCC is a rare subtype of malignant renal tumor. The diagnosis mainly relies on pathological morphology, immunohistochemistry, and the detection of TFE3 gene disruption by FISH. In terms of treatment, surgery is the primary approach, and lymph nodes, liver, and bone are the main metastatic sites. VEGFR-TKI+ICI treatment might be an option of recurrent or metastatic TFE3-rRCC.

PMID:39111254 | DOI:10.1016/j.clgc.2024.102165

Permalink for 'Survival and Prognostic Factors after Adrenalectomy for Secondary Malignancy: A Combined Analysis of a French University Center Registry (Eurocrine Â®) of 307 Patients and a French Nationwide Study of 2,515 Patients'

Survival and Prognostic Factors after Adrenalectomy for Secondary Malignancy: A Combined Analysis of a French University Center Registry (Eurocrine Â®) of 307 Patients and a French Nationwide Study of 2,515 Patients

Fetched: August 8th, 2024, 2:00am UTC by Agathe RÃ©mond

Ann Surg. 2024 Aug 7. doi: 10.1097/SLA.0000000000006479. Online ahead of print.

ABSTRACT

OBJECTIVE: To provide a nationwide description of postoperative outcomes and analysis of prognostic factors following adrenalectomy for metastases.

SUMMARY BACKGROUND DATA: Adrenal glands are a common site of metastases in many malignancies. Diagnosisof adrenal metastases is on the rise, leading to an increasing number of patient candidates for surgery without consensual management.

METHODS: We conducted a population-based study between January 2012 and December 2022 using the French national health data system (SNDS) and the EurocrineÂ® registry (NCT03410394). The first database exhaustively covers all procedures carried out in France, while the second provides more clinical information on procedures and tumor characteristics, based on the experience of 11 specialized centers.

RESULTS: From the SNDS, we extracted 2,515 patients who underwent adrenalectomy for secondary malignancy and 307 from the EurocrineÂ® database. The most common primary malignancies were lung cancer (n=1,203, 47.8%) and renal cancer (n=555, 22.1%). One-year survival was 84.3% (n=2,120). Thirty-day mortality and morbidity rates were, respectively, 1.3% (n=32) and 29.9% (n=753, including planned ICU stays). Radiotherapy within the year before adrenalectomy was significantly associated with higher 30-day major complication rates (P=0.039). In the EurocrineÂ® database, the proportion of laparoscopic procedures reached 85.3% without impairing resection completeness (R0: 92.9%). Factors associated with poor overall survival were presence of extra-adrenal metastases (HR=0.64; P=0.031) and incomplete resection (â‰¥R1; HR=0.41; P=0.015).

CONCLUSION: The number of patients who can receive local treatment for adrenal metastases is rising, and adrenalectomy is more often minimally invasive and has a low morbidity rate. Subsequent research should evaluate which patients would benefit from adrenal surgery.

PMID:39109429 | DOI:10.1097/SLA.0000000000006479

Adrenocortical carcinoma: selective internal radiation therapy and liver metastases

Fetched: August 8th, 2024, 2:00am UTC by Leo Baxendale-Smith

Endocr Oncol. 2024 Jul 8;4(1):e230041. doi: 10.1530/EO-23-0041. eCollection 2024 Jan 1.

ABSTRACT

Selective internal radiation therapy (SIRT) is a novel intervention for both primary and metastatic malignant liver lesions. Adrenocortical carcinoma (ACC) is rare with limited treatment options; evidence for SIRT in ACC liver metastases consists of case reports only. Selective internal radiation therapy (SIRT) was employed to treat recurrent liver metastases in a 49-year-old gentleman with ACC, who previously underwent a left-sided hepatectomy. The patient opted for SIRT after reviewing the literature regarding mitotane chemotherapy and its toxicities. Selective internal radiation therapy (SIRT) provided several months of progression-free survival (PFS), with no toxicity and an excellent radiological response. The patient re-presented 12 years after the initial diagnosis with skeletal metastases and sadly died in September 2022. Substantial unmet need exists for effective treatments in ACC, with 75% of patients presenting with incurable disease. Developing widespread disease, SIRT offered 2 years' PFS in our patient; this was well tolerated with minimal residual liver impairment. Its use in ACC liver-limited disease warrants investigation.

SIGNIFICANCE STATEMENT: Adrenocortical carcinoma (ACC) is a rare and aggressive tumour with limited treatments. Once metastatic disease develops, existing standard-of-care treatments offer a dismal overall survival, alongside marked toxicities. Selective internal radiation therapy (SIRT) may represent a new intervention in the treatment paradigm for liver-limited, metastatic ACC. Here, we present the case of a patient treated with multiple rounds of SIRT for relapsed, liver-limited ACC, prolonging survival by several years. Recurrent SIRT led to maintained liver function and no toxicities. Little evidence outlines its use in ACC but further study is certainly warranted to ascertain the value of SIRT, considering the limited treatment landscape that currently exists.

PMID:39108463 | PMC:PMC11301532 | DOI:10.1530/EO-23-0041

Adrenocortical carcinoma: what you at least should know

Fetched: August 7th, 2024, 2:00am UTC by Charles de Ponthaud

Br J Surg. 2024 Aug 2;111(8):znae177. doi: 10.1093/bjs/znae177.

NO ABSTRACT

PMID:39107063 | DOI:10.1093/bjs/znae177

Permalink for 'Diagnosis and management of patients with pheochromocytoma/paraganglioma: Consensus of experts of the Russian Medical Society for Arterial Hypertension and the Multidisciplinary Group for the Diagnosis and Treatment of Neuroendocrine Tumors'

Diagnosis and management of patients with pheochromocytoma/paraganglioma: Consensus of experts of the Russian Medical Society for Arterial Hypertension and the Multidisciplinary Group for the Diagnosis and Treatment of Neuroendocrine Tumors

Fetched: August 7th, 2024, 2:00am UTC by N V Blinova

Ter Arkh. 2024 Jul 30;96(7):645-658. doi: 10.26442/00403660.2024.07.202779.

ABSTRACT

The understanding of the nature of catecholamine-secreting tumors has changed significantly in recent years, affecting terminology and classification. Phaeochromocytoma/paraganglioma (PCC/PG) is a rare neuroendocrine tumor from chromaffin tissue that produces and secretes catecholamines. The incidence of PCC/PG is relatively low, with 2-8 cases per 1 million population per year; among patients with arterial hypertension, their prevalence is 0.2-0.6%. However, delayed diagnosis of PCC/PG is associated with a high risk of cardiovascular complications and a high mortality rate. The consensus presents the clinical manifestations of the disease with an emphasis on the course of arterial hypertension as the most common symptom in PCC/PG; modern ideas about the features of diagnosis, aspects of preoperative preparation, treatment, and follow-up of patients with PCC/PG are considered.

PMID:39106507 | DOI:10.26442/00403660.2024.07.202779

Hif-2Î± programmes oxygen chemosensitivity in chromaffin cells

Fetched: August 7th, 2024, 2:00am UTC by Maria Prange-Barczynska

J Clin Invest. 2024 Aug 6:e174661. doi: 10.1172/JCI174661. Online ahead of print.

ABSTRACT

The study of transcription factors that determine specialised neuronal functions has provided invaluable insights into the physiology of the nervous system. Peripheral chemoreceptors are neurone-like electro-physiologically excitable cells that link the oxygen content of arterial blood to the neuronal control of breathing. In the adult, this oxygen chemosensitivity is exemplified by the Type I cells of the carotid body and recent work has revealed one isoform of the transcription factor HIF, HIF-2Î±, to have a non-redundant role in the development and function of that organ. Here we show that the activation of HIF-2Î±, including isolated overexpression alone, is sufficient to induce oxygen chemosensitivity in the otherwise unresponsive adult adrenal medulla. This phenotypic change in the adrenal medulla was associated with retention of extra-adrenal paraganglioma-like tissues that resemble the foetal organ of Zuckerkandl and also manifest oxygen chemosensitivity. Acquisition of chemosensitivity was associated with changes in the adrenal medullary expression of classes of genes that are ordinarily characteristic of the carotid body, including G-protein regulators and atypical subunits of mitochondrial cytochrome oxidase. Overall, the findings suggest that, at least in certain tissues, HIF-2Î± acts as a phenotypic driver for cells that display oxygen chemosensitivity, thus linking two major oxygen sensing systems.

PMID:39106106 | DOI:10.1172/JCI174661

Agnostic Therapy in Rare Solid Tumors

Posted: October 14th, 2024, 11:00pm UTC

SCINTIX [BgRT} Using RMRS in Solid and Soft Tissue Tumors

Posted: October 10th, 2024, 11:00pm UTC

Trial for Local Ablative Treatment (LAT) Optimization in Patients With Advanced Non-Small Cells Lung Cancer (NSCLC) Presenting an Anaplastic Lymphoma Kinase (ALK) Rearrangement Treated by Brigatinib

Posted: October 1st, 2024, 11:00pm UTC

Phase II Study of PD-1 Antibody Combined with Radiotherapy in Recurrent or Metastatic Adrenal Cortical Carcinoma

Posted: September 9th, 2024, 11:00pm UTC

Conditions: Adrenocortical Carcinoma
Interventions: Drug: Triprolizumab; Device: rodiotherapy
Sponsors: Sun Yat-sen University
Not yet recruiting

Cadonilimab With Chemoradiation for Recurrent and Oligometastatic Endometrial Carcinoma

Posted: August 1st, 2024, 11:00pm UTC

Impact of Antihypertensive Therapy on Recurrence Risk of Ovarian Cancer for Bevacizumab-associated Hypertension

Posted: July 23rd, 2024, 11:00pm UTC

18F-Fibroblast Activation Protein Inhibitor ([18F]FAPI-74) PET Imaging for Cancer Detection

Posted: July 16th, 2024, 11:00pm UTC

Study of Preoperative Radiation Therapy in Participants With Resectable Recurrent Abdominal Adrenocortical Carcinoma

Posted: July 4th, 2024, 11:00pm UTC

[212Pb]VMT-Alpha-NET in Metastatic or Inoperable Somatostatin-Receptor Positive Gastrointestinal Neuroendocrine Tumors, Pheochromocytoma/Paragangliomas, Small Cell Lung, Renal Cell, and Head and Neck Cancers

Posted: June 28th, 2024, 11:00pm UTC

Synergistic Effects of PD-1 Antibody and Chemotherapy Followed by Surgery in Limited-metastatic G/GEJ Adenocarcinoma

Posted: June 21st, 2024, 11:00pm UTC

The Optimal Number of Fiducial Marker for Stereotactic Body Radiotherapy

Posted: April 2nd, 2024, 11:00pm UTC

Conditions: Lung Cancer; Liver Cancer; Pancreatic Cancer; Renal Cell Carcinoma
Interventions: Radiation: SBRT
Sponsors: Peking University Third Hospital
Recruiting

Dostarlimab for Locally Advanced or Metastatic Cancer (Non-colorectal/Non-endometrial) With Tumor dMMR/MSI

Posted: March 27th, 2024, 11:00pm UTC

Adrenal Project: Clinical and Epidemiological Characterization of Adrenocortical Carcinoma in a Brazilian Cohort

Posted: February 28th, 2024, 1:00am UTC

Conditions: Carcinoma Adrenal; Carcinoma, Adrenocortical Recurrent
Sponsors: Latin American Cooperative Oncology Group
Not yet recruiting

Development of Clinical Evidence for Optimal Management of Adrenal Diseases Based on Real-World Data

Posted: January 29th, 2024, 1:00am UTC

Stereotactic Ablative Radiotherapy in Synchronous and Metachronous Oligo-Metastatic Non Small Cell Lung Cancer

Posted: January 15th, 2024, 1:00am UTC

Local Therapy for Oligometastatic Esophageal Squamous Cell Cancer Patients Treated With PD-1 Inhibitor: a Prospective, Randomized, Phase III Clinical Trial.

Posted: January 4th, 2024, 1:00am UTC

Treatment of Advanced Endocrine Tumor With Iindividualized mRNA Neoantigen Vaccine (mRNA-0523-L001)

Posted: November 21st, 2023, 1:00am UTC

Study of Radiotherapy and Pembrolizumab in People With Adrenocortical Carcinoma

Posted: October 4th, 2023, 11:00pm UTC

A Phase 1, First in Human Study of TORL-4-500 in Patients With Advanced Cancer

Posted: August 22nd, 2023, 11:00pm UTC

Conditions: Advanced Solid Tumor; Hepatocellular Carcinoma
Interventions: Drug: TORL-4-500
Sponsors: TORL Biotherapeutics, LLC; Translational Research in Oncology
Recruiting

Phase 1 Study of 68Ga-R8760

Posted: August 21st, 2023, 11:00pm UTC

Evaluation of the Efficacy of Addition of Progesterone to Standard Chemotherapy in Adrenocortical Carcinoma (ACC)

Posted: June 22nd, 2023, 11:00pm UTC

NAC- NAFLD And Cushing

Posted: May 30th, 2023, 11:00pm UTC

Conditions: Cushing Syndrome; Fatty Liver Disease
Interventions: Diagnostic Test: hepatic MRI
Sponsors: University Hospital, Angers
Recruiting

18F-FDGal PET/CT and PET/MRI in Patients With Hepatocellular Carcinoma

Posted: May 23rd, 2023, 11:00pm UTC

Conditions: Hepatocellular Carcinoma
Interventions: Diagnostic Test: 18F-FDGal PET/CT or PET/MRI
Sponsors: University of Aarhus
Recruiting

Intratumoral Gemcitabine, Paclitaxel, Carboplatine and Intravenous Nivolumab for Locally Recurrence of Head and Neck Cancers

Posted: April 28th, 2023, 11:00pm UTC

Positioning of Molecular Markers in Clinical Routine for the Management of Patients With Adrenal Cancers/Tumors (COMETE-CARE)

Posted: March 6th, 2023, 1:00am UTC

A Multicentre Study on Features of the Gut Microbiota of Patients With Critical Chronic Diseases in China

Posted: December 6th, 2022, 1:00am UTC

A Phase II Study to Evaluate the Efficacy and Safety of Pembrolizumab in Combination With Mitotane in Patients With Advanced Adrenocortical Carcinoma

Posted: December 2nd, 2022, 1:00am UTC

Conditions: Adrenocortical Carcinoma
Interventions: Drug: Mitotane; Drug: Pembrolizumab
Sponsors: M.D. Anderson Cancer Center
Completed

Tissue Procurement and Natural History Study of Neuroendocrine Neoplasms (NENs) Including Adrenocortical Carcinoma (ACC)

Posted: February 14th, 2022, 1:00am UTC

Conditions: Neuroendocrine Tumors; Carcinoma, Neuroendocrine
Sponsors: National Cancer Institute (NCI)
Recruiting

Stereotactic MRI-guided Adaptive Radiation Therapy (SMART) in One Fraction

Posted: June 25th, 2021, 11:00pm UTC

Conditions: Metastatic Carcinoma
Interventions: Radiation: Stereotactic ablative body radiation therapy
Sponsors: Baptist Health South Florida; Viewray Inc.
Active, not recruiting

B7-H3-Specific Chimeric Antigen Receptor Autologous T-Cell Therapy for Pediatric Patients With Solid Tumors (3CAR)

Posted: May 21st, 2021, 11:00pm UTC

Conditions: Pediatric Solid Tumor; Osteosarcoma; Rhabdomyosarcoma; Neuroblastoma; Ewing Sarcoma; Wilms Tumor; Adrenocortical Cancer; Desmoplastic Small Round Cell Tumor; Germ Cell Cancer; Rhabdoid Tumor; Clear Cell Sarcoma; Hepatoblastoma; Melanoma; Carcinoma; Malignant Peripheral Nerve Sheath Tumors; Soft Tissue Sarcoma
Interventions: Drug: Fludarabine; Drug: Cyclophosphamide; Drug: MESNA; Drug: B7-H3 CAR T cells
Sponsors: St. Jude Children's Research Hospital
Recruiting

Permalink for 'Anti-CTLA4-NF mAb (BMS986218), Nivolumab, and Stereotactic Body Radiation Therapy for the Treatment of Metastatic Solid Malignancies'

Anti-CTLA4-NF mAb (BMS986218), Nivolumab, and Stereotactic Body Radiation Therapy for the Treatment of Metastatic Solid Malignancies

Posted: March 5th, 2021, 1:00am UTC

Conditions: Advanced Lung Carcinoma; Advanced Malignant Solid Neoplasm; Malignant Adrenal Gland Neoplasm; Metastatic Liver Carcinoma; Metastatic Lung Carcinoma; Metastatic Malignant Solid Neoplasm; Stage III Liver Cancer; Stage III Lung Cancer AJCC v8; Stage IIIA Lung Cancer AJCC v8; Stage IIIB Lung Cancer AJCC v8; Stage IIIC Lung Cancer AJCC v8; Stage IV Liver Cancer; Stage IV Lung Cancer AJCC v8; Stage IVA Liver Cancer; Stage IVA Lung Cancer AJCC v8; Stage IVB Liver Cancer; Stage IVB Lung Cancer AJCC v8
Interventions: Biological: Anti-CTLA4 Monoclonal Antibody BMS-986218; Biological: Nivolumab; Radiation: Stereotactic Body Radiation Therapy
Sponsors: M.D. Anderson Cancer Center
Active, not recruiting

Characterization of Biophysical Stromal Properties in Human Cancer: Towards Personalized Computational Oncology

Posted: August 13th, 2020, 11:00pm UTC

Conditions: Carcinomatosis, Peritoneal; Pancreas Cancer; Ovarian Cancer; Colon Cancer
Interventions: Procedure: MRI
Sponsors: University Hospital, Ghent
Recruiting

Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers

Posted: July 7th, 2020, 11:00pm UTC

Conditions: Bladder Carcinoma; Cervical Carcinoma; Cholangiocarcinoma; Hematopoietic and Lymphoid Cell Neoplasm; Hepatocellular Carcinoma; Malignant Adrenal Gland Neoplasm; Malignant Brain Neoplasm; Malignant Pleural Neoplasm; Malignant Skin Neoplasm; Malignant Solid Neoplasm; Malignant Testicular Neoplasm; Malignant Thymus Neoplasm; Neuroendocrine Neoplasm; Thyroid Gland Carcinoma; Urothelial Carcinoma; Cancer of Unknown Primary Site
Interventions: Procedure: Computed Tomography; Drug: Gallium Ga 68 FAPi-46; Procedure: Positron Emission Tomography; Radiation: 18F-FDG
Sponsors: Jonsson Comprehensive Cancer Center
Recruiting

Permalink for 'Study of Relacorilant in Combination With Pembrolizumab for Patients With Adrenocortical Carcinoma Which Produces Too Much Stress Hormone (Cortisol)'

Study of Relacorilant in Combination With Pembrolizumab for Patients With Adrenocortical Carcinoma Which Produces Too Much Stress Hormone (Cortisol)

Posted: May 4th, 2020, 11:00pm UTC

Conditions: Adrenocortical Carcinoma
Interventions: Drug: Relacorilant; Drug: Pembrolizumab
Sponsors: Corcept Therapeutics
Completed

Optimal Methods of Disease Progression and Survival Analysis in Children and Adults Patients With Adrenocortical Cancer (ACC)

Posted: April 22nd, 2020, 11:00pm UTC

Conditions: Adrenocortical Carcinoma
Sponsors: National Cancer Institute (NCI)
Active, not recruiting

Permalink for 'Phase II Study for Combination of Camrelizumab and Apatinib in the Second-line Treatment of Recurrent or Metastatic Adrenocortical Carcinoma'

Phase II Study for Combination of Camrelizumab and Apatinib in the Second-line Treatment of Recurrent or Metastatic Adrenocortical Carcinoma

Posted: March 24th, 2020, 11:00pm UTC

Conditions: Adrenocortical Carcinoma
Interventions: Drug: Camrelizumab
Sponsors: West China Hospital
Recruiting

A Novel Therapeutic Vaccine (EO2401) in Metastatic Adrenocortical Carcinoma, or Malignant Pheochromocytoma/Paraganglioma

Posted: December 5th, 2019, 1:00am UTC

Conditions: Adrenocortical Carcinoma; Pheochromocytoma; Paraganglioma
Interventions: Biological: EO2401; Biological: Nivolumab
Sponsors: Enterome
Active, not recruiting

Gene Modified Immune Cells (IL13Ralpha2 CAR T Cells) After Conditioning Regimen for the Treatment of Stage IIIC or IV Melanoma

Posted: October 8th, 2019, 11:00pm UTC

Conditions: Metastatic Malignant Solid Neoplasm; Metastatic Melanoma; Pathologic Stage IIIC Cutaneous Melanoma AJCC v8; Pathologic Stage IV Cutaneous Melanoma AJCC v8; Recurrent Malignant Solid Neoplasm; Refractory Malignant Solid Neoplasm; Uveal Melanoma; Acral Melanoma; Neuroendocrine Tumors; Paraganglioma; Pheochromocytoma; Adrenocortical Carcinoma; Pancreatic Neuroendocrine Tumor; Thyroid Cancer; Breast Cancer; Lung Adenocarcinoma; Head and Neck Squamous Cell Carcinoma
Interventions: Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Other: Fludeoxyglucose F-18; Biological: IL13Ralpha2-specific Hinge-optimized 4-1BB-co-stimulatory CAR/Truncated CD19-expressing Autologous TN/MEM Cells; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography
Sponsors: Jonsson Comprehensive Cancer Center; Parker Institute for Cancer Immunotherapy; City of Hope National Medical Center; Melanoma Research Alliance; California Institute for Regenerative Medicine (CIRM)
Recruiting

Stereotactic Magnetic Resonance Guided Radiation Therapy

Posted: October 3rd, 2019, 11:00pm UTC

Conditions: Pancreas Cancer; Lung Cancer; Renal Cancer; Adrenal Metastases; Prostate Cancer; Liver Metastases; Oligoprogressive Nodal Metastases; Metachronous Nodal Metastases; Synchronous Nodal Metastases; Mesothelioma; Spine Metastases; Brain Metastases; Borderline Resectable Pancreatic Carcinoma
Interventions: Radiation: MR-guided Linac
Sponsors: Dana-Farber Cancer Institute
Suspended

Permalink for 'A Study of Osimertinib With or Without Chemotherapy as 1st Line Treatment in Patients With Mutated Epidermal Growth Factor Receptor Non-Small Cell Lung Cancer (FLAURA2)'

A Study of Osimertinib With or Without Chemotherapy as 1st Line Treatment in Patients With Mutated Epidermal Growth Factor Receptor Non-Small Cell Lung Cancer (FLAURA2)

Posted: July 29th, 2019, 11:00pm UTC

Conditions: Non-Small Cell Lung Cancer
Interventions: Drug: Osimertinib; Drug: Pemetrexed/Carboplatin; Drug: Pemetrexed/Cisplatin
Sponsors: AstraZeneca
Active, not recruiting

A Study of ASP1951 in Subjects With Advanced Solid Tumors

Posted: January 10th, 2019, 1:00am UTC

Conditions: Advanced Solid Tumors
Interventions: Drug: ASP1951; Drug: pembrolizumab
Sponsors: Astellas Pharma Global Development, Inc.; Merck Sharp & Dohme LLC
Terminated

MyVHL: Patient Natural History Study

Posted: November 21st, 2018, 1:00am UTC

Conditions: Von Hippel-Lindau Disease; Hereditary Leiomyomatosis and Renal Cell Cancer; Birt-Hogg-Dube Syndrome; SDHB Gene Mutation
Sponsors: Joshua Mann, MPH; National Organization for Rare Disorders
Recruiting

SABR for Renal Tumors

Posted: November 20th, 2018, 1:00am UTC

Conditions: Renal Tumor
Interventions: Radiation: Stereotactic Ablative Radiotherapy
Sponsors: University Health Network, Toronto
Recruiting

A Phase 1/2 Study of [225Ac]-FPI-1434 Injection

Posted: November 19th, 2018, 1:00am UTC

Conditions: Advanced Solid Tumours; Endometrial Cancer; Cervical Cancer; Ovarian Cancer; Breast Cancer; Triple Negative Breast Cancer (TNBC); HER2-negative Breast Cancer; Head and Neck Squamous Cell Carcinoma (HNSCC); Adrenocortical Carcinoma; Uveal Melanoma
Interventions: Drug: [111In]-FPI-1547 Injection; Drug: [225Ac]-FPI-1434 Injection multi-dose; Biological: FPI-1175 Infusion; Drug: [225Ac]-FPI-1434 Injection single-dose
Sponsors: Fusion Pharmaceuticals Inc.
Recruiting

Natural History and Biospecimen Acquisition for Children and Adults With Rare Solid Tumors

Posted: November 14th, 2018, 1:00am UTC

Conditions: Malignant Solid Tumors; Other Neoplasms Solid Tumors; Pediatric Solid Tumor; Refractory Solid Tumors; Solid Tumor
Sponsors: National Cancer Institute (NCI)
Recruiting

Adjuvant Chemotherapy vs. Observation/Mitotane After Primary Surgical Resection of Localized Adrenocortical CarcInoma

Posted: October 30th, 2018, 11:00pm UTC

Conditions: Adrenocortical Carcinoma
Interventions: Drug: Cisplatin plus Etoposide; Other: Observation or Mitotane
Sponsors: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Completed

Descriptive Observational Study ALK-2016-CPHG

Posted: October 24th, 2018, 11:00pm UTC

Conditions: NSCLC; Crizotinib; ALK Gene Rearrangement or ROS1 Gene Rearrangement
Sponsors: Pfizer; French College of General Hospital Pneumologists (CPHG)
Completed

Cabozantinib in Advanced Adrenocortical Carcinoma

Posted: August 2nd, 2018, 11:00pm UTC

Conditions: Adrenocortical Carcinoma
Interventions: Drug: Cabozantinib-s-malate
Sponsors: Wuerzburg University Hospital
Active, not recruiting

Permalink for 'A Comparison of Platinum-based Therapy With TSR-042 and Niraparib Versus Standard of Care (SOC) Platinum-based Therapy as First-line Treatment of Stage III or IV Nonmucinous Epithelial Ovarian Cancer'

A Comparison of Platinum-based Therapy With TSR-042 and Niraparib Versus Standard of Care (SOC) Platinum-based Therapy as First-line Treatment of Stage III or IV Nonmucinous Epithelial Ovarian Cancer

Posted: July 27th, 2018, 11:00pm UTC

Conditions: Ovarian Neoplasms; Ovarian, Fallopian Tube and Primary Peritoneal Carcinoma
Interventions: Drug: Niraparib; Drug: Dostarlimab (TSR-042); Drug: Standard of care; Drug: Dostarlimab-Placebo; Drug: Niraparib-Placebo
Sponsors: Tesaro, Inc.; European Network of Gynaecological Oncological Trial Groups (ENGOT)
Active, not recruiting

Permalink for 'Mitotane With or Without Cisplatin and Etoposide After Surgery in Treating Patients With Stage I-III Adrenocortical Cancer With High Risk of Recurrence'

Mitotane With or Without Cisplatin and Etoposide After Surgery in Treating Patients With Stage I-III Adrenocortical Cancer With High Risk of Recurrence

Posted: July 11th, 2018, 11:00pm UTC

Conditions: ENSAT Stage I Adrenal Cortex Carcinoma; ENSAT Stage II Adrenal Cortex Carcinoma; ENSAT Stage III Adrenal Cortex Carcinoma
Interventions: Drug: Cisplatin; Drug: Etoposide; Drug: Mitotane; Other: Quality-of-Life Assessment
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI); Assistance Publique - HÃ´pitaux de Paris
Recruiting

Permalink for 'A Study of ASP1948, Targeting an Immune Modulatory Receptor as a Single Agent and in Combination With a PD-l Inhibitor (Nivolumab or Pembrolizumab) in Subjects With Advanced Solid Tumors'

A Study of ASP1948, Targeting an Immune Modulatory Receptor as a Single Agent and in Combination With a PD-l Inhibitor (Nivolumab or Pembrolizumab) in Subjects With Advanced Solid Tumors

Posted: June 21st, 2018, 11:00pm UTC

Conditions: Advanced Solid Tumors
Interventions: Drug: ASP1948; Drug: nivolumab; Drug: pembrolizumab
Sponsors: Astellas Pharma Global Development, Inc.; Merck Sharp & Dohme LLC
Completed

Cabozantinib in Treating Patients With Locally Advanced or Metastatic Unresectable Adrenocortical Carcinoma

Posted: December 12th, 2017, 1:00am UTC

Conditions: Metastatic Carcinoma in the Adrenal Cortex; Stage III Adrenal Cortex Carcinoma AJCC v8; Stage IV Adrenal Cortex Carcinoma AJCC v8; Unresectable Adrenal Cortex Carcinoma
Interventions: Drug: Cabozantinib; Other: Pharmacogenomic Study; Other: Pharmacokinetic Study
Sponsors: M.D. Anderson Cancer Center
Completed

Nivolumab Combined With Ipilimumab for Patients With Advanced Rare Genitourinary Tumors

Posted: November 7th, 2017, 1:00am UTC

Conditions: Genitourinary Cancer; Adrenocortical Carcinoma; Non-urothelial Bladder; Non-urothelial Upper Tract; Penile Cancer; Non-adenocarcinoma Prostate Cancer; Refractory Germ-cell; High Grade Neuroendocrine Carcinoma/Small Cell Carcinoma
Interventions: Drug: Ipilimumab; Drug: Nivolumab
Sponsors: Dana-Farber Cancer Institute; Bristol-Myers Squibb
Active, not recruiting

Surgery and Heated Intraperitoneal Chemotherapy for Adrenocortical Carcinoma

Posted: April 25th, 2017, 11:00pm UTC

Conditions: Adrenocortical Carcinoma; Peritoneal Carcinomatosis
Interventions: Drug: Cisplatin; Drug: Sodium thiosulfate; Procedure: Cytoreductive surgery
Sponsors: Columbia University
Recruiting

Familial Investigations of Childhood Cancer Predisposition

Posted: February 10th, 2017, 1:00am UTC

Conditions: Acute Leukemia; Adenomatous Polyposis; Adrenocortical Carcinoma; AML; BAP1 Tumor Predisposition Syndrome; Carney Complex; Choroid Plexus Carcinoma; Constitutional Mismatch Repair Deficiency Syndrome; Diamond-Blackfan Anemia; DICER1 Syndrome; Dyskeratosis Congenita; Emberger Syndrome; Familial Acute Myeloid Leukemia; Familial Adenomatous Polyposis; Fanconi Anemia; Familial Cancer; Familial Wilms Tumor; Familial Neuroblastoma; GIST; Hereditary Breast and Ovarian Cancer; Hereditary Paraganglioma-Pheochromocytoma Syndrome; Hodgkin Lymphoma; Juvenile Polyposis; Li-Fraumeni Syndrome; Lynch Syndrome; MDS; Melanoma Syndrome; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2; Neuroblastoma; Neurofibromatosis Type 1; Neurofibromatosis Type II; Nevoid Basal Cell Carcinoma Syndrome; Non Hodgkin Lymphoma; Noonan Syndrome and Other Rasopathy; Overgrowth Syndromes; Pancreatic Cancer; Peutz-Jeghers Syndrome; Pheochromocytoma/Paraganglioma; PTEN Hamartoma Tumor Syndrome; Retinoblastoma; Rhabdoid Tumor Predisposition Syndrome; Rhabdomyosarcoma; Rothmund-Thomson Syndrome; Tuberous Sclerosis; Von Hippel-Lindau Disease
Sponsors: St. Jude Children's Research Hospital
Recruiting

$Permalink for 'Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors'$

Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors

Posted: August 16th, 2016, 11:00pm UTC

Conditions: Adrenal Cortical Carcinoma; Alveolar Soft Part Sarcoma; Central Nervous System Neoplasm; Childhood Clear Cell Sarcoma of Soft Tissue; Clear Cell Sarcoma of Soft Tissue; Ewing Sarcoma; Hepatoblastoma; Hepatocellular Carcinoma; Osteosarcoma; Recurrent Adrenal Cortical Carcinoma; Recurrent Alveolar Soft Part Sarcoma; Recurrent Clear Cell Sarcoma of Soft Tissue; Recurrent Ewing Sarcoma; Recurrent Hepatoblastoma; Recurrent Hepatocellular Carcinoma; Recurrent Kidney Wilms Tumor; Recurrent Malignant Solid Neoplasm; Recurrent Osteosarcoma; Recurrent Primary Malignant Central Nervous System Neoplasm; Recurrent Renal Cell Carcinoma; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Recurrent Thyroid Gland Medullary Carcinoma; Refractory Adrenal Cortical Carcinoma; Refractory Alveolar Soft Part Sarcoma; Refractory Clear Cell Sarcoma of Soft Tissue; Refractory Ewing Sarcoma; Refractory Hepatoblastoma; Refractory Hepatocellular Carcinoma; Refractory Malignant Solid Neoplasm; Refractory Osteosarcoma; Refractory Primary Central Nervous System Neoplasm; Refractory Primary Malignant Central Nervous System Neoplasm; Refractory Renal Cell Carcinoma; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma; Refractory Thyroid Gland Medullary Carcinoma; Refractory Wilms Tumor; Renal Cell Carcinoma; Rhabdomyosarcoma; Soft Tissue Sarcoma; Solid Neoplasm; Thyroid Gland Medullary Carcinoma; Wilms Tumor
Interventions: Drug: Cabozantinib; Drug: Cabozantinib S-malate; Other: Pharmacological Study
Sponsors: National Cancer Institute (NCI)
Active, not recruiting

Nivolumab and Ipilimumab in Treating Patients With Rare Tumors

Posted: July 15th, 2016, 11:00pm UTC

Conditions: Acinar Cell Carcinoma; Adenoid Cystic Carcinoma; Adrenal Cortical Carcinoma; Adrenal Gland Pheochromocytoma; Anal Canal Neuroendocrine Carcinoma; Anal Canal Undifferentiated Carcinoma; Angiosarcoma; Apocrine Neoplasm; Appendix Mucinous Adenocarcinoma; Bartholin Gland Transitional Cell Carcinoma; Basal Cell Carcinoma; Bladder Adenocarcinoma; Breast Metaplastic Carcinoma; Cervical Adenocarcinoma; Cholangiocarcinoma; Chordoma; Colorectal Squamous Cell Carcinoma; Desmoid Fibromatosis; Endometrial Transitional Cell Carcinoma; Endometrioid Adenocarcinoma; Esophageal Neuroendocrine Carcinoma; Esophageal Undifferentiated Carcinoma; Extrahepatic Bile Duct Carcinoma; Extramammary Paget Disease; Fallopian Tube Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Fibromyxoid Tumor; Gallbladder Carcinoma; Gastric Neuroendocrine Carcinoma; Gastric Squamous Cell Carcinoma; Gastric Undifferentiated Carcinoma; Gastrointestinal Stromal Tumor; Gestational Trophoblastic Tumor; Giant Cell Carcinoma; Human Papillomavirus-Independent Cervical Adenocarcinoma, Clear Cell-Type; Intestinal Neuroendocrine Carcinoma; Intrahepatic Cholangiocarcinoma; Lung Neuroendocrine Tumor; Lung Sarcomatoid Carcinoma; Major Salivary Gland Carcinoma; Malignant Odontogenic Neoplasm; Malignant Peripheral Nerve Sheath Tumor; Malignant Solid Neoplasm; Malignant Testicular Sex Cord-Stromal Tumor; Metastatic Malignant Neoplasm of Unknown Primary; Metastatic Pituitary Neuroendocrine Tumor; Minimally Invasive Lung Adenocarcinoma; Mixed Mesodermal (Mullerian) Tumor; Mucinous Adenocarcinoma; Mucinous Cystadenocarcinoma; Nasal Cavity Adenocarcinoma; Nasal Cavity Carcinoma; Nasopharyngeal Carcinoma; Nasopharyngeal Low Grade Papillary Adenocarcinoma; Nasopharyngeal Undifferentiated Carcinoma; Oral Cavity Carcinoma; Oropharyngeal Undifferentiated Carcinoma; Ovarian Adenocarcinoma; Ovarian Germ Cell Tumor; Ovarian Mucinous Adenocarcinoma; Ovarian Squamous Cell Carcinoma; Ovarian Transitional Cell Carcinoma; Pancreatic Acinar Cell Carcinoma; Pancreatic Neuroendocrine Carcinoma; Paraganglioma; Paranasal Sinus Adenocarcinoma; Paranasal Sinus Carcinoma; Parathyroid Gland Carcinoma; PEComa; Penile Squamous Cell Carcinoma; Peritoneal Mesothelial Neoplasm; Placental Choriocarcinoma; Primary Peritoneal High Grade Serous Adenocarcinoma; Pseudomyxoma Peritonei; Rare Disorder; Scrotal Squamous Cell Carcinoma; Seminal Vesicle Adenocarcinoma; Seminoma; Serous Cystadenocarcinoma; Small Intestinal Adenocarcinoma; Small Intestinal Squamous Cell Carcinoma; Spindle Cell Neoplasm; Teratoma With Somatic-Type Malignancy; Testicular Non-Seminomatous Germ Cell Tumor; Thyroid Gland Carcinoma; Tracheal Carcinoma; Transitional Cell Carcinoma; Ureter Adenocarcinoma; Ureter Squamous Cell Carcinoma; Urethral Adenocarcinoma; Urethral Squamous Cell Carcinoma; Vaginal Adenocarcinoma; Vaginal Squamous Cell Carcinoma, Not Otherwise Specified; Vulvar Carcinoma
Interventions: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Echocardiography; Biological: Ipilimumab; Procedure: Magnetic Resonance Imaging; Biological: Nivolumab
Sponsors: National Cancer Institute (NCI)
Active, not recruiting

Single Agent Pembrolizumab in Subjects With Advanced Adrenocortical Carcinoma

Posted: February 3rd, 2016, 1:00am UTC

Conditions: Adrenocortical Carcinoma
Interventions: Drug: Pembrolizumab
Sponsors: Memorial Sloan Kettering Cancer Center; Merck Sharp & Dohme LLC
Active, not recruiting

Permalink for 'Effect of Cabozantinib S-Malate or Lenvatinib Mesylate on Weight and Body Composition in Patients With Metastatic Endocrine Cancer'

Effect of Cabozantinib S-Malate or Lenvatinib Mesylate on Weight and Body Composition in Patients With Metastatic Endocrine Cancer

Posted: October 30th, 2015, 11:00pm UTC

Conditions: Differentiated Thyroid Gland Carcinoma; Malignant Adrenal Gland Pheochromocytoma; Malignant Paraganglioma; Thyroid Gland Medullary Carcinoma
Interventions: Procedure: Computed Tomography; Procedure: Dual X-ray Absorptiometry; Procedure: Physical Examination; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Cabozantinib; Drug: Lenvatinib
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Completed

Project: Every Child for Younger Patients With Cancer

Posted: March 30th, 2015, 11:00pm UTC

Conditions: Adrenal Gland Pheochromocytoma; Carcinoma In Situ; Central Nervous System Neoplasm; Childhood Immature Teratoma; Childhood Langerhans Cell Histiocytosis; Childhood Mature Teratoma; Congenital Mesoblastic Nephroma; Desmoid Fibromatosis; Ganglioneuroma; Lymphoproliferative Disorder; Malignant Neoplasm; Malignant Solid Neoplasm; Melanocytic Neoplasm; Myeloproliferative Neoplasm; Neoplasm of Uncertain Malignant Potential; Neuroendocrine Neoplasm; Stromal Neoplasm
Interventions: Other: Cytology Specimen Collection Procedure; Other: Medical Chart Review
Sponsors: Children's Oncology Group; National Cancer Institute (NCI)
Recruiting

Visualizing Vascular Endothelial Growth Factor (VEGF) Producing Lesions in Von Hippel-Lindau Disease

Posted: September 3rd, 2009, 11:00pm UTC

Conditions: Von Hippel-Lindau Disease; Hemangioblastoma; Renal Cell Carcinoma; Pheochromocytoma; Pancreatic Neuroendocrine Tumor
Interventions: Other: 89Zr bevacizumab PET scan
Sponsors: University Medical Center Groningen; VHL Alliance
Completed

Adrenal Tumors - Pathogenesis and Therapy

Posted: April 30th, 2008, 11:00pm UTC

Conditions: Adrenal Tumors; Adrenocortical Carcinoma; Cushing Syndrome; Conn Syndrome; Pheochromocytoma
Sponsors: University of Wuerzburg; Deutsche Krebshilfe e.V., Bonn (Germany); German Federal Ministry of Education and Research
Recruiting

Evaluation of Side Effects of Mitotane

Posted: December 5th, 2007, 1:00am UTC

Conditions: Adrenocortical Carcinoma
Sponsors: University of Wuerzburg
Active, not recruiting

Preclinical Study Towards an Immunotherapy in Adrenocortical Carcinoma

Posted: April 6th, 2007, 11:00pm UTC

Conditions: Adrenocortical Carcinoma; Cushing's Syndrome
Sponsors: University of Wuerzburg; Deutsche Krebshilfe e.V., Bonn (Germany)
Recruiting

German Adrenocortical Carcinoma Registry

Posted: March 29th, 2007, 11:00pm UTC

Conditions: Adrenocortical Carcinoma
Sponsors: University of Wuerzburg; Deutsche Krebshilfe e.V., Bonn (Germany)
Recruiting

Cisplatin-Based Chemotherapy and/or Surgery in Treating Young Patients With Adrenocortical Tumor

Posted: March 17th, 2006, 1:00am UTC

Conditions: Stage I Adrenal Cortical Carcinoma AJCC v7; Stage II Adrenal Cortical Carcinoma AJCC v7; Stage III Adrenal Cortical Carcinoma AJCC v7; Stage IV Adrenal Cortical Carcinoma AJCC v7
Interventions: Drug: Cisplatin; Procedure: Conventional Surgery; Drug: Doxorubicin Hydrochloride; Drug: Etoposide; Biological: Filgrastim; Drug: Mitotane; Biological: Pegfilgrastim
Sponsors: Children's Oncology Group; National Cancer Institute (NCI)
Completed

Permalink for 'The impact of acyl-CoA:cholesterol transferase (ACAT) inhibitors on biophysical membrane properties depends on membrane lipid composition'

The impact of acyl-CoA:cholesterol transferase (ACAT) inhibitors on biophysical membrane properties depends on membrane lipid composition

Fetched: October 16th, 2024, 2:00am UTC by Huong To

Mol Cell Endocrinol. 2024 Oct 13:112385. doi: 10.1016/j.mce.2024.112385. Online ahead of print.

ABSTRACT

Acyl-coenzyme A: cholesterol acyltransferases are enzymes which are involved in the homeostasis of cholesterol. Impaired enzyme activity is associated with the occurrence of various diseases like Alzheimer's disease, atherosclerosis, and cancers. At present, mitotane is the only inhibitor of this class of enzymes in clinical use for the treatment of adrenocortical carcinoma but associated with common and severe adverse effects. The therapeutic effect of mitotane depends on its interaction with cellular membranes. The search for less toxic but equally effective compounds is hampered by an incomplete understanding of these biophysical properties. In the present study, the interaction of the three ACAT inhibitors nevanimibe, Sandoz 58-035, and AZD 3988 with membranes has been investigated using lipid model membranes in conjunction with biophysical experimental (NMR, ESR, fluorescence) and theoretical (MD simulations) approaches. The data show, that the drugs (i) incorporate into lipid membranes, (ii) differently influence the structure of lipid membranes; (iii) affect membrane structure depending on the lipid composition; and (iv) do not cause hemolysis of red blood cells. The results are discussed with regard to the use of the drugs, in particular to better understand their efficacy and possible side effects.

PMID:39406287 | DOI:10.1016/j.mce.2024.112385

AGO2 protein: a key enzyme in the miRNA pathway as a novel biomarker in adrenocortical carcinoma

Fetched: October 16th, 2024, 2:00am UTC by Anila Hashmi

Endocr Relat Cancer. 2024 Oct 1:ERC-24-0061. doi: 10.1530/ERC-24-0061. Online ahead of print.

ABSTRACT

PMID:39404265 | DOI:10.1530/ERC-24-0061

EBNA1BP2 identified as potential prognostic biomarker for multiple tumor types in pan-cancer analysis

Fetched: October 16th, 2024, 2:00am UTC by Li-Yue Sun

Discov Oncol. 2024 Oct 11;15(1):549. doi: 10.1007/s12672-024-01326-0.

ABSTRACT

BACKGROUND: Epstein-Barr virus (EBV) infection has been closely linked to the development of various types of cancer. EB nuclear antigen 1 binding protein 2 (EBNA1BP2) is a crucial molecule for stable isolation of EBV in latent infection. However, the role of EBNA1BP2 in multiple tumor types is remains unclear. In this study, we comprehensively analyzed the functional characteristics of EBNA1BP2 and investigate its potential as a prognostic biomarker in pan-cancer.

METHODS: We utilized data from TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus) databases and employed various bioinformatics analysis tools, including TIMER2.0, HPA, GEPIA2.0, PrognoScan, cBioPortal, CancerSEA, and BioGRID to explore the expression pattern, prognostic value, immune infiltration, and methylation level of EBNA1BP2 in pan-cancer. Additionally, we conducted enrichment analysis of genes associated with EBNA1BP2 to identify potential biological functions and pathways.

RESULTS: Our analysis revealed that EBNA1BP2 expression was significantly higher in tumor tissues compared to tumor-adjacent tissues. We observed that lower expression of EBNA1BP2 in adrenocortical carcinoma (ACC), brain lower grade glioma (LGG), sarcoma (SARC), and uterine carcinosarcoma (UCS) was significantly associated with improved overall survival (OS) and disease-free survival (DFS). Furthermore, the promoter methylation level of EBNA1BP2 was downregulated in the majority of cancer types. At the single-cell level, EBNA1BP2 was found to be positively correlated with cell cycle and DNA repair processes, while negatively correlated with hypoxia. Additionally, EBNA1BP2 was associated with the infiltration of immune cells such as B cells, cancer-associated fibroblast cells, and CD8+ T cells. Gene enrichment analysis indicated that EBNA1BP2 was mainly involved in nucleoplasm and RNA binding pathways.

CONCLUSION: Our findings suggest that EBNA1BP2 may serve as a potential prognostic biomarker for survival in pan-cancer. Further experimental studies are needed to validate these findings and explore the underlying mechanisms by which EBNA1BP2 contributes to tumorigenesis.

PMID:39394548 | PMC:PMC11469992 | DOI:10.1007/s12672-024-01326-0

The molecular genetics of adrenal cushing

Fetched: October 16th, 2024, 2:00am UTC by Patricia Vaduva

Hormones (Athens). 2024 Oct 10. doi: 10.1007/s42000-024-00608-0. Online ahead of print.

ABSTRACT

PMID:39388056 | DOI:10.1007/s42000-024-00608-0

Role of radiologists in the diagnosis and management of adrenal disorders

Fetched: October 16th, 2024, 2:00am UTC by Sota Oguro

Endocr J. 2024 Oct 10. doi: 10.1507/endocrj.EJ24-0156. Online ahead of print.

ABSTRACT

This study aimed to focus on the role of radiologists in the diagnosis and management of adrenal lesions, particularly primary aldosteronism (PA) and secondary hypertension. As hypertension affects more than one-third of the population in Japan, identifying secondary causes such as PA and adrenal lesions is crucial. Establishing a radiological differential diagnosis of adrenal lesions using advanced imaging techniques, such as computed tomography and magnetic resonance imaging, is crucial. Knowledge of the imaging findings of various benign and malignant adrenal lesions, such as adrenocortical adenomas, cortisol-producing lesions, pheochromocytomas, adrenocortical carcinoma, malignant lymphoma, and metastatic tumors, is necessary. Adrenal venous sampling (AVS) plays a crucial role in accurately localizing aldosterone hypersecretion in PA, especially when imaging fails to provide a clear diagnosis. This paper details the technical aspects of AVS, emphasizing catheterization techniques, anatomical considerations, and the importance of preprocedural imaging for successful sampling. Furthermore, we explore segmental adrenal venous sampling (SAVS), a more refined technique that samples specific adrenal tributary veins, offering enhanced diagnostic accuracy, particularly for microadenomas or challenging cases that may be missed with conventional AVS. The methodology for performing SAVS, along with the interpretation criteria for successful sampling and lateralization, is also outlined. Furthermore, radiologists have initiated treatments for unilateral PA, such as radiofrequency ablation, and play an integral role in the management of adrenal lesions. Collaborative approaches across clinical departments are required to enhance patient management in medical care involving the adrenal gland.

PMID:39384399 | DOI:10.1507/endocrj.EJ24-0156

Texture analysis can predict response to etoposide-doxorubicin-cisplatin in patients with adrenocortical carcinoma

Fetched: October 16th, 2024, 2:00am UTC by Filippo CrimÃ¬

J Endocrinol Invest. 2024 Oct 9. doi: 10.1007/s40618-024-02476-2. Online ahead of print.

ABSTRACT

BACKGROUND: The adrenocortical carcinoma (ACC) is a rare and highly aggressive malignancy originating from the adrenal cortex. These patients usually undergo chemotherapy with etoposide, doxorubicin, cisplatin and mitotane (EDP-M) in case of locally advanced or metastatic ACC. Computed tomography (CT) radiomics showed to be useful in adrenal pathologies. The study aimed to analyze the association between response to EDP-M treatment and CT textural features at diagnosis in patients with locally advanced or metastatic ACCs.

METHODS: We enrolled 17 patients with advanced or metastatic ACC who underwent CT before and after EDP-M therapy. The response to treatment was evaluated according to RECIST 1.1, Choi, and volumetric criteria. Based on the aforementioned criteria, the patients were classified as responders and not responders. Textural features were extracted from the biggest lesion in contrast-enhanced CT images with LifeX software. ROC curves were drawn for the variables that were significantly different (p < 0.05) between the two groups.

RESULTS: Long-run high grey level emphasis (LRHGLE_GLRLM) and histogram kurtosis were significantly different between responder and not responder groups (p = 0.04) and the multivariate ROC curve combining the two features showed a very good AUC (0.900; 95%IC: 0.724-1.000) in discriminating responders from not responders. More heterogeneous tissue texture of initial staging CT in locally advanced or metastatic ACC could predict the positive response to EDP-M treatment.

CONCLUSIONS: Adrenal texture is able to predict the response to EDP-M therapy in patients with advanced ACC.

PMID:39382628 | DOI:10.1007/s40618-024-02476-2

Adrenocortical neoplasm in a 2-year-old child: Clinical approach and diagnostic imaging

Fetched: October 16th, 2024, 2:00am UTC by Nathalia Sofia Coral-Rivera

Radiol Case Rep. 2024 Sep 25;19(12):6417-6422. doi: 10.1016/j.radcr.2024.09.116. eCollection 2024 Dec.

ABSTRACT

PMID:39380812 | PMC:PMC11460622 | DOI:10.1016/j.radcr.2024.09.116

Permalink for 'The efficacy of adjuvant mitotane therapy and radiotherapy following adrenalectomy in patients with adrenocortical carcinoma: A systematic review and meta-analysis'

The efficacy of adjuvant mitotane therapy and radiotherapy following adrenalectomy in patients with adrenocortical carcinoma: A systematic review and meta-analysis

Fetched: October 16th, 2024, 2:00am UTC by Ichiro Tsuboi

Urol Oncol. 2024 Oct 7:S1078-1439(24)00654-9. doi: 10.1016/j.urolonc.2024.09.014. Online ahead of print.

ABSTRACT

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with a high recurrence rate after surgical therapy with curative intent. Adjuvant radiotherapy (RT) and mitotane therapy have been proposed as options following the adrenalectomy. However, the efficacy of adjuvant RT or mitotane therapy remains controversial. We aimed to evaluate the efficacy of adjuvant therapy in patients who underwent adrenalectomy for localised ACC. The PubMed, Scopus, and Web of Science databases were queried on March 2024 for studies evaluating adjuvant therapies in patients treated with surgery for localized ACC (PROSPERO: CRD42024512849). The endpoints of interest were overall survival (OS) and recurrence-free survival (RFS). Hazard ratios (HR) with 95% confidence intervals (95%CI) were pooled in a random-effects model meta-analysis. One randomized controlled trial (n = 91) and eleven retrospective studies (n = 4,515) were included. Adjuvant mitotane therapy was associated with improved RFS (HR: 0.63, 95%CI: 0.44-0.92, p = 0.016), while adjuvant RT did not reach conventional levels of statistical significance (HR:0.79, 95%CI:0.58-1.06, p = 0.11). Conversely, Adjuvant RT was associated with improved OS (HR:0.69, 95%CI:0.58-0.83, p<0.001), whereas adjuvant mitotane did not (HR: 0.76, 95%CI: 0.57-1.02, p = 0.07). In the subgroup analyses, adjuvant mitotane was associated with better OS (HR:0.46, 95%CI: 0.30-0.69, p < 0.001) and RFS (HR:0.56, 95%CI: 0.32-0.98, p = 0.04) in patients with negative surgical margin. Both adjuvant RT and mitotane were found to be associated with improved oncologic outcomes in patients treated with adrenalectomy for localised ACC. While adjuvant RT significantly improved OS in general population, mitotane appears as an especially promising treatment option in patients with negative surgical margin. These data can support the shared decision-making process, better understanding of the risks, benefits, and effectiveness of these therapies is still needed to guide tailored management of each individual patient.

PMID:39379210 | DOI:10.1016/j.urolonc.2024.09.014

Permalink for 'Molecular Subtypes Defined by Cuproptosis-Associated Genes, Prognostic Model Development, and Tumor Immune Microenvironment Characterization in Adrenocortical Carcinoma'

Molecular Subtypes Defined by Cuproptosis-Associated Genes, Prognostic Model Development, and Tumor Immune Microenvironment Characterization in Adrenocortical Carcinoma

Fetched: October 16th, 2024, 2:00am UTC by Qi Huang

J Inflamm Res. 2024 Oct 3;17:7017-7036. doi: 10.2147/JIR.S461489. eCollection 2024.

ABSTRACT

INTRODUCTION: This study aims to explore the role of cuproptosis-related genes in ACC, utilizing data from TCGA and GEO repositories, and to develop a predictive model for patient stratification.

METHODS: A cohort of 123 ACC patients with survival data was analyzed. RNA-seq data of 17 CRGs were examined, and univariate Cox regression identified prognostic CRGs. A cuproptosis-related network was constructed to show interactions between CRGs. Consensus clustering classified ACC into three subtypes, with transcriptional and survival differences assessed by PCA and survival analysis. Gene set variation analysis (GSVA) and ssGSEA evaluated functional and immune infiltration characteristics across subtypes. Differentially expressed genes (DEGs) were identified, and gene clusters were established. A risk score (CRG_score) was generated using LASSO and multivariate Cox regression, validated across datasets. Tumor microenvironment, stem cell index, mutation status, drug sensitivity, and hormone synthesis were examined in relation to the CRG_score. Protein expression of key genes was validated, and functional studies on ASF1B and NDRG4 were performed.

RESULTS: Three ACC subtypes were identified with distinct survival outcomes. Subtype B showed the worst prognosis, while subtype C had the best. We identified 214 DEGs linked to cell proliferation and classified patients into three gene clusters, confirming their prognostic value. The CRG_score predicted patient outcomes, with high-risk patients demonstrating worse survival and possible resistance to immunotherapy. Drug sensitivity analysis suggested higher responsiveness to doxorubicin and etoposide in high-risk patients.

CONCLUSION: This study suggests the potential prognostic value of CRGs in ACC. The CRG_score model provides a robust tool for risk stratification, with implications for treatment strategies.

PMID:39377045 | PMC:PMC11457769 | DOI:10.2147/JIR.S461489

Which lymphadenectomy for adrenocortical carcinoma?

Fetched: October 16th, 2024, 2:00am UTC by Charles de Ponthaud

Surgery. 2024 Oct 5:S0039-6060(24)00716-5. doi: 10.1016/j.surg.2024.09.008. Online ahead of print.

ABSTRACT

BACKGROUND: Lymph node dissection improves adrenocortical carcinoma staging, but remains anatomically poorly defined. This ambiguity stems from limited knowledge of the adrenals lymphatic network. This work aims to define lymph node dissection for adrenocortical carcinoma through a systematic review and anatomical study.

METHOD: First, an anatomical study was conducted on fresh cadavers by injecting blue dye into each adrenal gland before dissection. Concurrently, a systematic review of anatomical and clinical studies was performed, focusing on adrenals lymphatic network, lymph node dissection, and location of invaded lymph nodes in surgical series.

RESULTS: Twelve adrenals from 6 cadavers were resected en bloc with a median of 3 lymph nodes (1.5-6) removed. Screening of 6,506 studies revealed (1) 18 anatomical studies on cadavers detailing a 3-stage compartmentalized adrenals lymphatic network with distinct right/left lymph nodes relays; (2) 4 clinical studies highlighting discrepancies in lymph node involvement in adrenocortical carcinoma patients compared with anatomical description of adrenals lymphatic network, notably: lower implication of celiac lymph node, preponderance of ipsilateral renal hilum lymph nodes, potential contralateral involvement; (3) 21 series of adrenocortical carcinoma surgery demonstrating the heterogeneity of lymph node dissection practice (22% Â± 4% lymph node dissection rate), with an average of 2.7 Â± 0.6 lymph nodes removed, already fewer than in our cadaveric study.

CONCLUSION: Synthesis of anatomical and clinical studies suggest the following lymph node dissection protocol during adrenocortical carcinoma resection: capsular, renal hilum, para-cava, and inter-aortic-cava lymph nodes (right adrenocortical carcinoma); and capsular, renal hilum, para-aortic, and inter-aortic-cava lymph nodes (left adrenocortical carcinoma).

PMID:39370320 | DOI:10.1016/j.surg.2024.09.008

Permalink for 'Robotic lateral resection of inferior vena cava extended to liver segment 7 for adrenocortical carcinoma recurrence (with video)'

Robotic lateral resection of inferior vena cava extended to liver segment 7 for adrenocortical carcinoma recurrence (with video)

Fetched: October 16th, 2024, 2:00am UTC by Jacques-Emmanuel Saadoun

J Visc Surg. 2024 Oct 4:S1878-7886(24)00100-0. doi: 10.1016/j.jviscsurg.2024.07.007. Online ahead of print.

NO ABSTRACT

PMID:39368937 | DOI:10.1016/j.jviscsurg.2024.07.007

Influence of sex and functional status on the value of serum steroid profiling in discriminating adrenocortical carcinoma from adrenocortical adenoma

Fetched: October 16th, 2024, 2:00am UTC by Yan Weng

Front Endocrinol (Lausanne). 2024 Sep 18;15:1435102. doi: 10.3389/fendo.2024.1435102. eCollection 2024.

ABSTRACT

PMID:39359414 | PMC:PMC11445004 | DOI:10.3389/fendo.2024.1435102

Benign pure androgen-secreting adrenal tumor misdiagnosed as adrenocortical carcinoma on (18)F-FDG PET-CT: a rare case report

Fetched: October 16th, 2024, 2:00am UTC by Zhan Wang

Endocrine. 2024 Sep 30. doi: 10.1007/s12020-024-04059-w. Online ahead of print.

ABSTRACT

BACKGROUND: Adult pure androgen-secreting adrenal tumors (PASATs) are rarely reported and the malignancy of such tumor are difficult to confirm before surgery. Here we report a PASAT demonstrating extremely ¹⁸F-FDG uptake turned out to benign tumor by postoperative pathology examination.

CASE PRESENTATION: A 19-year-old adolescent found a tumor measuring 7.2 cm located in the right adrenal region on enhanced CT during the routine physical examination. Signs of virilization and elevated testosterone and dehydroepiandrosterone (DHEA) were verified during preoperative examination. ¹⁸F-FDG PET/CT revealed the tumor had an extremely high ¹⁸F-FDG uptake with a SUVmax reaching 42.7, which turned out to be oncocytic adrenocortical adenoma by pathological examination.

CONCLUSIONS: ¹⁸F-FDG PET/CT may be limited in assessing the malignancy of PASAT.

PMID:39347912 | DOI:10.1007/s12020-024-04059-w

Permalink for 'Inpatient palliative care in metastatic adrenocortical carcinoma: a retrospective analysis using the National Inpatient Sample database'

Inpatient palliative care in metastatic adrenocortical carcinoma: a retrospective analysis using the National Inpatient Sample database

Fetched: October 16th, 2024, 2:00am UTC by Letizia M Jannello

Minerva Endocrinol (Torino). 2024 Sep 30. doi: 10.23736/S2724-6507.24.04185-X. Online ahead of print.

ABSTRACT

BACKGROUND: The use of inpatient palliative care (IPC) in advanced cancer patients represents a well-established guideline recommendation. This study examines the utilization rates and patterns of IPC among patients with metastatic adrenocortical carcinoma (mACC).

METHODS: Relying on the Nationwide Inpatient Sample database (2007-2019), we tabulated IPC rates in mACC patients. Estimated annual percentage changes (EAPC) analyses as well as multivariable logistic regression models (MLRM) predicting IPC use were fitted.

RESULTS: Of 2040 mACC patients, 238 (12%) received IPC. Overall, the rate of IPC increased from 3.7% to 19.1% between 2007 and 2019 (EAPC +9.6%, P=0.001). During the same period, in-hospital mortality remained unchanged from 12.1 to 13.8% (EAPC 0.1%; P=0.97). Younger age at admission (<60 years; MLRM OR=0.70, P=0.013), solitary metastatic site (OR=0.63; P=0.015), and non-brain metastases (OR=0.62; P=0.033) were all associated with lower IPC use.

CONCLUSIONS: In mACC patients, IPC use has increased from a marginal 3.7% to a moderate annual value of 19.1% in the most recent study year. These rates were not driven by a concomitant increase in in-hospital mortality (12.1% to 13.8%; P=0.9). and may be interpreted as an improvement in quality of care. Despite this encouraging increase, some patient characteristics herald lower IPC use. In consequence, younger patients, those with solitary metastatic sites, and non-brain metastases should be carefully considered for IPC to decrease or completely reduce the IPC access barrier maximally.

PMID:39345031 | DOI:10.23736/S2724-6507.24.04185-X

Powder Self-Emulsifying Drug Delivery System for Mitotane: In Vitro and In Vivo Evaluation

Fetched: October 16th, 2024, 2:00am UTC by Mohamed Skiba

Pharmaceutics. 2024 Sep 11;16(9):1194. doi: 10.3390/pharmaceutics16091194.

ABSTRACT

Drug Delivery Systems (DDSs) of known drugs are prominent candidates for new and more effective treatments of various diseases, as they may increase drug solubility, dissolution velocity, and bioavailability. Mitotane (o,p'-dichlorodimethyl dichloroethane [o,p'-DDD]) is used for the treatment of adrenocortical cancer and, occasionally, Cushing's syndrome. However, the efficacy of mitotane is limited by its low oral bioavailability, caused by its extremely poor aqueous solubility. This research explores the development of a new powder self-emulsifying drug delivery system (P-SEDDS) for mitotane to improve its oral bioavailability. The study focuses on the new concept of a mitotane-loaded P-SEDDS to overcome the challenges associated with its limited solubility and high logP, thereby improving its therapeutic efficacy, reducing off-target toxicity, and avoiding first-pass metabolism. The P-SEDDS formulations were meticulously designed using only Î±-cyclodextrin and oil, with the goal of achieving a stable and efficient P-SEDDS. The optimized formulation was characterized for pharmaceutical properties, and its pharmacokinetic behavior was examined in rats. The results demonstrated a significant enhancement in the bioavailability of mitotane when delivered through the P-SEDDS, attributed to the increased dissolution velocity and improved absorption of the poorly water-soluble drug. The results suggest that a mitotane-loaded P-SEDDS has distinctly enhanced in vitro and in vivo performance compared with conventional mitotane formulations (Lysodren^Â®), which leads to the conclusion that the P-SEDDS formulation could be a viable and effective strategy for improving the dissolution rate and bioavailability of poorly aqueous-soluble ingredients.

PMID:39339230 | PMC:PMC11434810 | DOI:10.3390/pharmaceutics16091194

The Modified S-GRAS Scoring System for Prognosis in Korean with Adrenocortical Carcinoma

Fetched: October 16th, 2024, 2:00am UTC by Sun Kyung Baek

Endocrinol Metab (Seoul). 2024 Sep 25. doi: 10.3803/EnM.2024.2086. Online ahead of print.

ABSTRACT

BACKGROUND: Adrenocortical carcinomas (ACCs) are rare tumors with aggressive but varied prognosis. Stage, Grade, Resection status, Age, Symptoms (S-GRAS) score, based on clinical and pathological factors, was found to best stratify the prognosis of European ACC patients. This study assessed the prognostic performance of modified S-GRAS (mS-GRAS) scores including modified grade (mG) by integrating mitotic counts into the Ki67 index (original grade), in Korean ACC patients.

METHODS: Patients who underwent surgery for ACC between January 1996 and December 2022 at three medical centers in Korea were retrospectively analyzed. mS-GRAS scores were calculated based on tumor stage, mG (Ki67 index or mitotic counts), resection status, age, and symptoms. Patients were divided into four groups (0-1, 2-3, 4-5, and 6-9 points) based on total mS-GRAS score. The associations of each variable and mS-GRAS score with recurrence and survival were evaluated using Cox regression analysis, Harrell's concordance index (C-index), and the Kaplan-Meier method.

RESULTS: Data on mS-GRAS components were available for 114 of the 153 patients who underwent surgery for ACC. These 114 patients had recurrence and death rates of 61.4% and 48.2%, respectively. mS-GRAS score was a significantly better predictor of recurrence (C-index=0.829) and death (C-index=0.747) than each component (P<0.05), except for resection status. mS-GRAS scores correlated with shorter progression-free survival (P=8.34E-24) and overall survival (P=2.72E-13).

CONCLUSION: mS-GRAS scores showed better prognostic performance than tumor stage and grade in Asian patients who underwent surgery for ACC.

PMID:39322187 | DOI:10.3803/EnM.2024.2086

ClickRNA-PROTAC for Tumor-Selective Protein Degradation and Targeted Cancer Therapy

Fetched: October 16th, 2024, 2:00am UTC by Xucong Teng

J Am Chem Soc. 2024 Oct 9;146(40):27382-27391. doi: 10.1021/jacs.4c06402. Epub 2024 Sep 25.

ABSTRACT

Proteolysis-targeting chimeras (PROTACs) show promise in tumor treatment. However, the E3 ligases VHL and CRBN, commonly used in PROTAC, are highly expressed in only a few tumors, thus limiting the application scope and efficacy of PROTAC drugs. Furthermore, the lack of tumor specificity in PROTAC drugs can result in toxic side effects. Therefore, there is an urgent need to develop tumor-selective PROTAC drugs that do not rely on endogenous E3 ligases. In this study, we introduce the ClickRNA-PROTAC system, which involves the expression of a fusion protein of the E3 ubiquitin ligase SIAH1 and SNAPTag through mRNA transfection and recruits the protein of interest (POI) using bio-orthogonal click chemistry. ClickRNA-PROTAC can effectively degrade various proteins such as BRD4, KRAS, and NFÎºB simply by replacing the warhead molecules. By employing a tumor-specific mRNA-responsive translation strategy, ClickRNA-PROTAC can selectively degrade POIs in tumor cells. Furthermore, ClickRNA-PROTAC demonstrated strong efficacy in targeted cancer therapy in a xenograft mouse model of adrenocortical carcinoma. In conclusion, this approach offers several advantages, including independence from endogenous E3 ubiquitin ligases, tumor specificity, and programmability, thereby paving the way for the development of PROTAC drugs.

PMID:39320981 | DOI:10.1021/jacs.4c06402

Permalink for 'Pan-cancer analysis of the role of Î±2C-adrenergic receptor (ADRA2C) in human tumors and validation in glioblastoma multiforme models'

Pan-cancer analysis of the role of Î±2C-adrenergic receptor (ADRA2C) in human tumors and validation in glioblastoma multiforme models

Fetched: October 16th, 2024, 2:00am UTC by Xiaoxiao Zhang

J Cancer. 2024 Sep 9;15(17):5691-5709. doi: 10.7150/jca.98240. eCollection 2024.

ABSTRACT

Background: Several studies have reported the relationship between Î±2C-adrenergic receptor (ADRA2C) and both neoplastic and non-neoplastic diseases. However, a comprehensive pan-cancer analysis is currently lacking. Methods: Utilizing the RNA sequencing (RNA-seq) datasets from The Cancer Genome Atlas (TCGA) database, the roles of ADRA2C in human pan-cancer were analyzed through a variety of bioinformatics approaches, including R programming language and single-cell sequencing data analysis, et al. Besides, cell migration assay and immunochemistry were employed to further validate the role of ADRA2C in glioblastoma multiforme (GBM) cell lines and GBM mouse model. Results: A total of 33 cancer types were involved in this study. It was revealed that the expression level of ADRA2C varied across different clinical stages in patients with breast invasive carcinoma (BRCA), esophageal adenocarcinoma (ESCA), kidney renal papillary cell carcinoma (KIRP) and lung squamous cell carcinoma (LUSC). Meanwhile, it was found that ADRA2C may play roles in prognosis of adrenocortical carcinoma (ACC), glioblastoma multiforme and lower grade glioma (GBM-LGG), and uveal melanoma (UVM). Functional enrichment analysis suggested that ADRA2C expression level was highly correlated with neuronal system-related pathways. Moreover, ADRA2C may be a promising diagnostic marker for cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), cholangiocarcinoma (CHOL), GBM, GBMLGG, kidney chromophobe (KICH), and KIRP. Additionally, ADRA2C expression level was correlated with the levels of several infiltrating cells and immune checkpoint genes. Besides, the single-cell sequencing data analysis indicated that ADRA2C played a role in multiple tumor development processes in GBM, retinoblastoma (RB), and UVM. Finally, in vitro and in vivo experiments confirmed that the expression level of ADRA2C may be associated with glioma cell migration, apoptosis, and invasion. Conclusion: ADRA2C exhibited to play a notable role in several cancer types, suggesting that ADRA2C could serve as a promising biomarker or target for cancer diagnosis, prognosis, and treatment, particularly for GBM.

PMID:39308687 | PMC:PMC11414618 | DOI:10.7150/jca.98240

[18F]FDG-PET/CT in adrenal lesions: diagnostic performance in different clinical settings

Fetched: October 16th, 2024, 2:00am UTC by Martina Romanisio

Endocrine. 2024 Sep 18. doi: 10.1007/s12020-024-04042-5. Online ahead of print.

ABSTRACT

PURPOSE: Data regarding [18^F]FDG-PET/CT for the characterization of adrenal lesions are limited. Most of the studies proposed the tumor-to-liver maximum standardized uptake values (SUVratio) > 1.5 as the best cut off to predict malignancy. The aim of the study was to calculate the optimum cut off in a heterogeneous population with adrenal lesions and evaluate the diagnostic performance SUVratio >1.5.

PATIENTS AND METHODS: Retrospective analysis of adrenal lesions undergoing [18^F]FDG-PET/CT (2013-2022) for different reasons (atypical adrenal incidentalomas, extra adrenal tumor staging). The diagnosis of benignity was assessed by: (i) histology; (ii) stability or minimal diameter increase (<20%/<5 mm) on 12-months follow-up for non-operated patients. The optimal SUVratio and performance of SUVratio >1.5 were calculated by ROC curves.

RESULTS: Forty-two consecutive lesions (diameter 36.1 Â± 20.3 mm, 6 bilateral) underwent [18^F]FDG-PET/CT (19F, age 61.2 Â± 11.7 years). Twenty-nine lesions were benign, 11 malignant [8 metastases (2 bilateral) and 1 adrenocortical carcinoma (ACC)] and 2 pheochromocytomas. The SUVratio cut-off in our population was 1.55 (Sn 100%, Sp 73.7%, AUC 0.868), with similar values excluding pheochromocytomas and metastases (SUVratio cut-off 1.49, Sn 100%, Sp 96.3%, AUC 0.988). The SUVratio cut-off of 1.5 showed 100% Sn, 87% Sp, 73% PPV, and 100% NPV.

CONCLUSION: [18^F]FDG-PET/CT could help in decision making process avoiding unnecessary surgery. The SUVratio cut-off of 1.5 has a good performance in a heterogenous population.

PMID:39294519 | DOI:10.1007/s12020-024-04042-5

Adrenocortical Carcinoma and the Mitotane Morass: A Physician/Patient Perspective

Fetched: October 16th, 2024, 2:00am UTC by David A Goodkin

Endocr Pract. 2024 Sep 16:S1530-891X(24)00672-4. doi: 10.1016/j.eprac.2024.09.006. Online ahead of print.

NO ABSTRACT

PMID:39293544 | DOI:10.1016/j.eprac.2024.09.006

Polish diagnostic and therapeutic recommendations for adrenocortical carcinoma

Fetched: October 16th, 2024, 2:00am UTC by Daria Handkiewicz-Junak

Endokrynol Pol. 2024;75(4):339-358. doi: 10.5603/ep.101677.

ABSTRACT

Advances in the diagnosis and treatment of adrenocortical carcinoma (ACC), along with the development of new therapeutic and diagnostic methods, have prompted a team of experts to formulate the first Polish guidelines for managing ACC. This article presents the diagnostic and therapeutic recommendations resulting from the discussion of specialists from various medical specialities, who participated in a series of online meetings aimed at developing consistent and effective recommendations under the National Oncology Strategy. These guidelines aim to optimise ACC treatment in Poland through coordinated efforts of multidisciplinary specialist teams, ensuring an effective and modern approach.

PMID:39279304 | DOI:10.5603/ep.101677

Adverse Events of Adjuvant Mitotane Treatment for Adrenocortical Carcinoma

Fetched: October 16th, 2024, 2:00am UTC by Ivana Dora VodanoviÄ‡

Endocr Res. 2024 Sep 15:1-7. doi: 10.1080/07435800.2024.2402311. Online ahead of print.

ABSTRACT

BACKGROUND: Mitotane is the cornerstone of adjuvant adrenocortical cancer (ACC) treatment. However, its use is burdened with frequent adverse events.

METHODS: A retrospective analysis of adverse events was performed in 26 ACC patients adjuvantly treated with mitotane.

RESULTS: Mitotane toxicity was present in all patients (100%). Two (7.7%) patients developed 1-3 adverse events, 15 (57.7%) experienced 4-6 adverse events and 9 (34.6%) patients had more than 6 adverse events. Two (7.7%) patients discontinued mitotane due to adverse events.

CONCLUSION: Careful monitoring and timely management are essential for ensuring mitotane treatment adherence and maximizing its benefits.

PMID:39277812 | DOI:10.1080/07435800.2024.2402311

A huge adrenocortical carcinoma mimicking liver mass

Fetched: October 16th, 2024, 2:00am UTC by N Aydinbelge-Dizdar

Rev Esp Med Nucl Imagen Mol (Engl Ed). 2024 Sep 11:500060. doi: 10.1016/j.remnie.2024.500060. Online ahead of print.

NO ABSTRACT

PMID:39270845 | DOI:10.1016/j.remnie.2024.500060

Pan-cancer analysis of m1A writer gene RRP8: implications for immune infiltration and prognosis in human cancers

Fetched: October 16th, 2024, 2:00am UTC by Zhihui Huang

Discov Oncol. 2024 Sep 12;15(1):437. doi: 10.1007/s12672-024-01299-0.

ABSTRACT

BACKGROUND: Ribosomal RNA Processing 8 (RRP8) is a gene associated with RNA modification and has been implicated in the development of several types of tumors in recent research. Nevertheless, the biological importance of RRP8 in pan-cancer has not yet been thoroughly and comprehensively investigated.

METHODS: In this study, we conducted an analysis of various public databases to investigate the biological functions of RRP8. Our analysis included examining its correlation with pan-cancer prognosis, heterogeneity, stemness, immune checkpoint genes, and immune cell infiltration. Furthermore, we utilized the GDSC and CTRP databases to assess the sensitivity of RRP8 to small molecule drugs.

RESULTS: Our findings indicate that RRP8 exhibits differential expression between tumor and normal samples, particularly impacting the prognosis of various cancers such as Adrenocortical carcinoma (ACC) and Kidney Chromophobe (KICH). The expression of RRP8 is intricately linked to tumor heterogeneity and stemness markers. Additionally, RRP8 shows a positive correlation with the presence of tumor-infiltrating cells, with TP53 being the predominant mutated gene in these malignancies.

CONCLUSION: Our findings suggest that RRP8 may serve as a potential prognostic marker and therapeutic target in a variety of cancer types.

PMID:39266915 | PMC:PMC11393379 | DOI:10.1007/s12672-024-01299-0

Pediatric Adrenocortical Carcinoma: The Nuts and Bolts of Diagnosis and Treatment and Avenues for Future Discovery

Fetched: October 16th, 2024, 2:00am UTC by Allison F O'Neill

Cancer Manag Res. 2024 Sep 7;16:1141-1153. doi: 10.2147/CMAR.S348725. eCollection 2024.

ABSTRACT

Adrenocortical tumors (ACTs) are infrequent neoplasms in children and adolescents and are typically associated with clinical symptoms reflective of androgen overproduction. Pediatric ACTs typically occur in the context of a germline TP53 mutation, can be cured when diagnosed at an early stage, but are difficult to treat when advanced or associated with concurrent TP53 and ATRX alterations. Recent work has demonstrated DNA methylation patterns suggestive of prognostic significance. While current treatment standards rely heavily upon surgical resection, chemotherapy, and hormonal modulation, small cohort studies suggest promise for multi-tyrosine kinases targeting anti-angiogenic pathways or immunomodulatory therapies. Future work will focus on novel risk stratification algorithms and combination therapies intended to mitigate toxicity for patients with perceived low-risk disease while intensifying therapy or accelerating discoveries aimed at improving survival for patients with difficult-to-treat disease.

PMID:39263332 | PMC:PMC11389717 | DOI:10.2147/CMAR.S348725

Permalink for 'Ruptured triple hormone-secreting adrenal cortical carcinoma with hyperaldosteronism, hypercortisolism, and elevated normetanephrine: a case report'

Ruptured triple hormone-secreting adrenal cortical carcinoma with hyperaldosteronism, hypercortisolism, and elevated normetanephrine: a case report

Fetched: October 16th, 2024, 2:00am UTC by Sin Yung Woo

J Yeungnam Med Sci. 2024 Oct;41(4):306-311. doi: 10.12701/jyms.2024.00626. Epub 2024 Sep 6.

ABSTRACT

We report a case of a ruptured triple hormone-secreting adrenal mass with hyperaldosteronism, hypercortisolism, and elevated normetanephrine levels, diagnosed as adrenal cortical carcinoma (ACC) by histology. A 53-year-old male patient who initially presented with abdominal pain was referred to our hospital for angiocoagulation of an adrenal mass rupture. Abdominal computed tomography revealed a heterogeneous 19Ã—11Ã—15 cm right adrenal mass with invasion into the right lobe of the liver, inferior vena cava, retrocaval lymph nodes, and aortocaval lymph nodes. Angiocoagulation was performed. Laboratory evaluation revealed excess cortisol via a positive 1-mg overnight dexamethasone suppression test, primary hyperaldosteronism via a positive saline infusion test, and plasma normetanephrine levels three times higher than normal. An adrenal mass biopsy was performed for pathological confirmation to commence palliative chemotherapy because surgical management was not deemed appropriate considering the extent of the tumor. Pathological examination revealed stage T4N1M1 ACC. The patient started the first cycle of adjuvant mitotane therapy along with adjuvant treatment with doxorubicin, cisplatin, and etoposide, and was discharged. Clinical cases of dual cortisol- and aldosterone-secreting ACCs or ACCs presenting as pheochromocytomas have occasionally been reported; however, both are rare. Moreover, to the best of our knowledge, a triple hormone-secreting ACC has not yet been reported. Here, we report a rare case and its management. This case report underscores the necessity of performing comprehensive clinical and biochemical hormone evaluations in patients with adrenal masses because ACC can present with multiple hormone elevations.

PMID:39238157 | DOI:10.12701/jyms.2024.00626

A puzzling malignant adrenal tumor

Fetched: October 16th, 2024, 2:00am UTC by Francisca de Brito Marques

Ann Endocrinol (Paris). 2024 Aug 28:S0003-4266(24)00706-6. doi: 10.1016/j.ando.2024.08.595. Online ahead of print.

ABSTRACT

A previously healthy 49-year-old male presented with abdominal pain, constitutional syndrome, paroxysmal palpitations and diaphoresis. Full-body CT scan showed a large malignant adrenal mass with abdominal lymph node and pulmonary metastasis. Biochemical studies revealed hypersecretion of catecholamines, cortisol, sexual steroids and steroid precursors; ACTH was not suppressed, and chromogranin A was negative. 18F-fluorodeoxyglucose PET/CT showed intense tracer uptake in the adrenal mass and abdominal lymph nodes. He was placed under adrenergic blockade and offered cytoreductive surgery, but his evolution was unfavorable with rapid clinical deterioration due to compressive abdominal symptoms, uncontrolled pain, peripheral oedema, cachexia and severe dilated cardiomyopathy. 123I-metaiodobenzylguanidine scintigraphy was negative. Poor clinical status precluded any surgical or systemic treatments. A biopsy of the adrenal mass suggested adrenocortical carcinoma. Two weeks later he developed recurrent level 3 non-insulin mediated hypoglycemias, with suppressed levels of insulin, C-peptide, IGF-1 and IGF-BP3. He responded poorly to palliative measures and died within a week, four months after the initial diagnosis. We present a puzzling case of an aggressive stage IV adrenal malignancy with bizarre secretory profile. Although we could not obtain a surgical specimen, combined available data suggested adrenocortical carcinoma. The pathophysiology is uncertain, and we explored exceedingly rare scenarios, including adrenocortical carcinoma masquerading as pseudo-pheochromocytoma; synchronous adrenocortical carcinoma and pheochromocytoma; adrenal mixed corticomedullary tumor; and ACTH-producing pheochromocytoma. The presence of ectopic ACTH-dependent hypercortisolism, discordant plasma and urinary metanephrine levels and IGF-2 mediated hypoglycemias were also quite perplexing. To our knowledge, this is the first report of a malignant adrenal tumor co-secreting steroid hormones with ACTH-dependent hypercortisolism, catecholamines and IGF-2. We faced obvious diagnostic and therapeutic challenges and encourage future studies to explore the complex interactions between cortical and chromaffin cells of the adrenal gland, that may have bidirectionally contributed to this patient's condition.

PMID:39232900 | DOI:10.1016/j.ando.2024.08.595

Advances in pathological diagnostic scoring systems and specific immune markers of adrenocortical carcinoma

Fetched: October 16th, 2024, 2:00am UTC by W T Gan

Zhonghua Bing Li Xue Za Zhi. 2024 Sep 8;53(9):968-972. doi: 10.3760/cma.j.cn112151-20240108-00018.

ABSTRACT

è‚¾ä¸Šè…ºçš®è´¨ç™Œï¼ˆACCï¼‰æ˜¯ä¸€ç§ç½•è§çš„è‚¾ä¸Šè…ºæ¶æ€§è‚¿ç˜¤ã€‚ç›®å‰ï¼ŒACCçš„è¯Šæ–æ ‡å‡†å°šæœªç»Ÿä¸€ï¼Œæœ‰åŒ…æ‹¬Weissè¯„åˆ†ç³»ç»Ÿåœ¨å†…çš„å¤šä¸ªè¯Šæ–æ ‡å‡†ï¼ŒåŒ…å«æ ¸åˆ†è£‚è±¡ã€åæ»åŠè¡€ç®¡ä¾µçŠ¯ç‰å¢žæ®–åŠä¾µè¢æ€§ç›¸å…³ç»„ç»‡å¦ç‰¹å¾ã€‚è¿‘å¹´æ¥å…³äºŽACCå…ç–«è¡¨åž‹çš„ç ”ç©¶é€æ¸å‘å±•ï¼Œç½‘çŠ¶çº¤ç»´æŸ“è‰²åŠå…ç–«ç»„ç»‡åŒ–å¦æ ‡å¿—ç‰©Ki-67ã€èƒ°å²›ç´ æ ·ç”Ÿé•¿å› å2ã€Î²-cateninã€p53ã€CYP11B1ã€DAXX/ATRXåŠé”™é…ä¿®å¤ç›¸å…³è›‹ç™½ç‰å‡è¢«å‘çŽ°ç”¨äºŽè¾…åŠ©ACCçš„è¯Šæ–ã€‚.

PMID:39231758 | DOI:10.3760/cma.j.cn112151-20240108-00018

Serum steroid profiling in the diagnosis of adrenocortical carcinoma: a prospective cohort study

Fetched: October 16th, 2024, 2:00am UTC by Kai Yu

J Clin Endocrinol Metab. 2024 Sep 4:dgae604. doi: 10.1210/clinem/dgae604. Online ahead of print.

ABSTRACT

CONTEXT: Guidelines suggest performing urine steroid profiling in patients with indeterminate adrenal tumors to make a noninvasive diagnosis of adrenocortical carcinoma (ACC). However, urine steroid profiling is not widely available.

OBJECTIVE: To determine the accuracy of clinically available serum 11-deoxycortisol, 17OH-progesterone, and 17OH-pregnenolone in diagnosing ACC.

METHODS: We conducted a prospective single-center cohort study of patients with adrenal masses evaluated between 2015-2023. Serum was analyzed by liquid chromatography-mass spectrometry for 17OH-pregnenolone, 17OH-progesterone, 11-deoxycortisol. Reference standard for adrenal mass included histopathology, imaging characteristics, imaging follow up of 2 years, or clinical follow up of 5 years. Localized Generalized Matrix Learning Vector Quantization (LGMLVQ) analysis was used to develop serum steroid score and assessed with area under receiver operating curve (AUROC).

RESULTS: Of 263 patients with adrenal masses, 44 (16.7%) were diagnosed with ACC, 161 (61%) with adrenocortical adenomas (ACAs), 27 (10%) with other adrenal malignancies, and 31 (12%) with other. Hounsfield unit (HU) â‰¥ 20 was demonstrated in all ACCs, in all but one other adrenal malignancy, and in 58 (31%) ACAs. All 3 steroids were higher in patients with ACCs vs non-ACCs, including when comparing ACCs with functioning ACAs, and with ACAs with HU â‰¥ 20 (P<0.0001 for all). LGMLVQ analysis yielded a serum steroid score that discriminated between ACC and non-ACC groups with a mean threshold fixed AUROC of 0.823.

CONCLUSIONS: We showed that measurements of 11-deoxycortisol, 17OH-progesterone, and 17OH-pregnenolone could be valuable in diagnosing ACC. After appropriate validation, serum steroid score could be integrated in clinical practice.

PMID:39231247 | DOI:10.1210/clinem/dgae604

Dlk1 is a novel adrenocortical stem/progenitor cell marker that predicts malignancy in adrenocortical carcinoma

Fetched: October 16th, 2024, 2:00am UTC by Katia Mariniello

bioRxiv [Preprint]. 2024 Aug 22:2024.08.22.609117. doi: 10.1101/2024.08.22.609117.

ABSTRACT

Disruption of processes involved in tissue development and homeostatic self-renewal is increasingly implicated in cancer initiation, progression, and recurrence. The adrenal cortex is a dynamic tissue that undergoes life-long turnover. Here, using genetic fate mapping and murine adrenocortical carcinoma (ACC) models, we have identified a population of adrenocortical stem cells that express delta-like non-canonical Notch ligand 1 (DLK1). These cells are active during development, near dormant postnatally but are re-expressed in ACC. In a study of over 200 human ACC samples, we have shown DLK1 expression is ubiquitous and is an independent prognostic marker of recurrence-free survival. Paradoxically, despite its progenitor role, spatial transcriptomic analysis has identified DLK1 expressing cell populations to have increased steroidogenic potential in human ACC, a finding also observed in four human and one murine ACC cell lines. Finally, the cleavable DLK1 ectodomain is measurable in patients' serum and can discriminate between ACC and other adrenal pathologies with high sensitivity and specificity to aid in diagnosis and follow-up of ACC patients. These data demonstrate a prognostic role for DLK1 in ACC, detail its hierarchical expression in homeostasis and oncogenic transformation and propose a role for its use as a biomarker in this malignancy.

PMID:39229217 | PMC:PMC11370565 | DOI:10.1101/2024.08.22.609117

Treatment Outcomes in Patients with Recurrent Adrenocortical Carcinoma

Fetched: September 3rd, 2024, 2:00am UTC by Tamara Dojcinovic

Endocr Res. 2024 Sep 2:1-7. doi: 10.1080/07435800.2024.2397561. Online ahead of print.

ABSTRACT

BACKGROUND: While numerous studies have explored treatment outcomes for the overall ACC patient cohort, data on the subpopulation of patients with recurrent disease are limited. Therefore, the aim of this study was to assess treatment outcomes in patients with recurrent ACC.

METHODS: In this retrospective study, we included 18 patients median age 49 years (42-62); 67% female) diagnosed with recurrent ENSAT stage I-III ACC who underwent either R0 (n = 16) or Rx (n = 2) surgical resection of the tumor.

RESULTS: The median time from the initial surgery to ACC recurrence was 29 months (IQR 18-50). Seven patients (39%) manifested local recurrence, while 11 patients (61%) developed distant metastases. The median follow-up duration after tumor recurrence was 32 months (IQR 25-53). Regarding the treatment of ACC recurrence, 10 patients underwent a second surgery either as an alone procedure (n = 4), or in combination with mitotane (n = 4), mitotane and chemotherapy (n = 1), or mitotane combined with radiotherapy (n = 1). The remaining patients received treatment involving chemotherapyÂ±mitotane (n = 4) and locoregional therapy Â±chemotherapy (n = 3). One patient chose not to proceed with further management and follow-up. The median PFS was 17 (95% CI 8-26) months while the median OS was not reached. In the multivariate model, increased mortality was associated with advanced age (p = 0.04) and a shorter interval to ACC recurrence (p = 0.03).

CONCLUSION: A significant proportion of patients with ACC recurrence experience disease progression or second recurrence, despite all treatment efforts. Nevertheless, by integrating diverse treatment modalities, many patients have the potential to attain long-term survival.

PMID:39221851 | DOI:10.1080/07435800.2024.2397561

Permalink for 'Etoposide, cisplatin, and sintilimab combined with anlotinib in successful treatment of adrenocortical carcinoma with lung metastasis: a case report'

Etoposide, cisplatin, and sintilimab combined with anlotinib in successful treatment of adrenocortical carcinoma with lung metastasis: a case report

Fetched: September 3rd, 2024, 2:00am UTC by Wenjing Niu

Front Oncol. 2024 Aug 16;14:1403762. doi: 10.3389/fonc.2024.1403762. eCollection 2024.

ABSTRACT

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare malignant tumor that occurs in the adrenal cortex. It has a high degree of malignancy and comparatively poor overall prognosis. Surgery is the standard curative therapy for localized ACC patients. The combination regimen of etoposide, doxorubicin, cisplatin (EDP) plus mitotane has been considered as the standardized chemotherapy regimen for advanced ACC. However, new effective regimens are emerging for specific conditions in metastatic ACC.

CASE PRESENTATION: We report a case of a 66-year-old man diagnosed with metastatic ACC who had a large left adrenal mass (110 mm Ã— 87 mm) and multiple metastases in both lungs. The patient was treated with EP and sintilimab for six cycles; anlotinib was introduced after the third cycle. Follow-ups after the second to fourth cycles found significantly reduced lung metastases with all imaging examinations indicating partial response (PR) status. The patient received maintenance therapy thereafter with sintilimab plus anlotinib. Until recently, the patient's lung metastases and the left adrenal gland area mass (39mm Ã— 29mm) have disappeared, and no disease progression has been observed. The progression-free survival of this patient has been extended to approximately 31 months, in sharp contrast to a median survival time of 12 months for majority of advanced ACC. The main adverse events during treatment were appetite loss and grade I myelosuppression and revealed only grade I hypertension and grade I hypothyroidism.

CONCLUSION: This case highlights the remarkable response of our patient's ACC to treatment with a novel combination of EP and sintilimab combined with anlotinib. Our findings suggest a safe and more effective combination therapeutic option for patients with adrenocortical carcinoma.

PMID:39220648 | PMC:PMC11361937 | DOI:10.3389/fonc.2024.1403762

Kidney sparing during surgical treatment of an adrenocortical carcinoma with renal vein invasion in a cat

Fetched: September 3rd, 2024, 2:00am UTC by Stefano Nicoli

Can Vet J. 2024 Sep;65(9):894-899.

ABSTRACT

PMID:39219601 | PMC:PMC11339906

Expression Patterns of MOTS-c in Adrenal Tumors: Results from a Preliminary Study

Fetched: September 1st, 2024, 2:00am UTC by Kacper KamiÅ„ski

Int J Mol Sci. 2024 Aug 9;25(16):8721. doi: 10.3390/ijms25168721.

ABSTRACT

PMID:39201408 | PMC:PMC11354279 | DOI:10.3390/ijms25168721

Neuroendocrine carcinoma of the adrenal gland: A rare case report and literature review

Fetched: August 27th, 2024, 2:00am UTC by Achmad Romy Syahrial Rozidi

Radiol Case Rep. 2024 Jul 30;19(10):4408-4412. doi: 10.1016/j.radcr.2024.06.079. eCollection 2024 Oct.

ABSTRACT

Neuroendocrine carcinoma (NEC) presence in the adrenal glands is rare. Neuroendocrine carcinoma manifests across a wide range of clinical presentations, from asymptomatic cases to those characterized by hormone overproduction or the tumor's mass effect. We report a 48-year-old male referred by a urology specialist with a chief complaint of right-sided back pain for the past 6 months accompanied by nausea, vomiting, and sharp stabbing headaches. The patient had a history of right adrenalectomy surgery. Elevated blood pressure of 150/110 mmHg, and no abnormalities found. The radiologist found a solid lesion and cyst at the lower pole of the right kidney and observed multiple recurrent tumors in the right adrenal on the MRI examination. The biopsy revealed poorly differentiated carcinoma and adrenocortical carcinoma tissue on the second biopsy 2 months later. The patient was diagnosed with neuroendocrine carcinoma; the patient underwent a biopsy guided by CT, followed by a pathological assessment (PA). The surgeon carried out the tumor removal surgery and performed an immunohistochemical (IHC) analysis. A 3-month follow-up is planned to evaluate the potential need for adjuvant chemotherapy. The case underscores the importance of accurate pathological diagnosis and multimodal management in recurrent adrenal tumors, particularly when considering NEC as a differential diagnosis.

PMID:39185439 | PMC:PMC11343998 | DOI:10.1016/j.radcr.2024.06.079

Rare adrenal schwannoma treated with robotic-assisted adrenalectomy: A case report

Fetched: August 24th, 2024, 2:00am UTC by Glendon Markollari

Urol Case Rep. 2024 Jul 22;56:102807. doi: 10.1016/j.eucr.2024.102807. eCollection 2024 Sep.

ABSTRACT

Schwannomas are benign neoplasms that arise from peripheral nerve sheaths. Typically found in peripheral nerves of the head, neck, and extremities, these tumors seldom arise in the retroperitoneum. We report the case of a 50-year-old male with a 5 cm right adrenal mass removed via robotic-assisted laparoscopic approach due to concerns for adrenocortical carcinoma, which surgical pathology revealed to be a rare adrenal schwannoma. This is the reported case.

PMID:39175937 | PMC:PMC11340595 | DOI:10.1016/j.eucr.2024.102807

$Permalink for 'Prognostic value of total, free and lipoprotein fraction-bound plasma mitotane levels in advanced adrenocortical carcinoma: a prospective study of the ENDOCAN-COMETE-Cancer network'$

Prognostic value of total, free and lipoprotein fraction-bound plasma mitotane levels in advanced adrenocortical carcinoma: a prospective study of the ENDOCAN-COMETE-Cancer network

Fetched: August 23rd, 2024, 2:00am UTC by M Faron

J Endocrinol Invest. 2024 Aug 22. doi: 10.1007/s40618-024-02439-7. Online ahead of print.

ABSTRACT

PURPOSE: Mitotane is the only approved treatment for metastatic adrenocortical carcinoma (ACC). Monitoring plasma levels is recommended, but its predictive value is insufficient.

METHODS: This prospective study of the French ENDOCAN-COMETE network aimed to investigate the prognostic role of plasma mitotane levels pharmacokinetics and free or bound to lipoprotein fraction measurements during six consecutive months. Lipoprotein fractions were isolated by ultracentrifugation, and mitotane level was determined by HPLC-UV. Total, free, and lipoprotein fraction bound plasma mitotane were monitored every two months for six months with morphological assessment. The primary endpoint was overall survival (OS).

RESULTS: 21 patients with metastatic ACC were included. Median overall survival was 23 months. The median free mitotane level per patient was 12% (Â± 7%), and the majority (88%) was bound to lipoprotein fractions. Several pharmacokinetics measures of total mitotane were related to OS: first level at one month (p = 0.026), mean level (p = 0.055), and area under the curve (AUC) (p = 0.048), with higher exposure associated to longer OS. Free mitotane (not bounded) and mitotane bounded to lipoprotein subfraction added no prognostic values. The relationship between the mitotane level and OS suggested a minimum "effective" threshold of 10-15 mg/L or an area under the curve above 100 mg/L/month with no individualized maximum value.

CONCLUSION: This prospective study did not identify any added prognostic value of free mitotane level over the total level. Early total mitotane level measurements (before 3-6 months) were related to OS with a higher and faster exposure related to more prolonged survival.

PMID:39172357 | DOI:10.1007/s40618-024-02439-7

Primary Unilateral Macronodular Adrenal Hyperplasia With Concomitant Glucocorticoid And Androgen Excess And KDM1A Inactivation

Fetched: August 23rd, 2024, 2:00am UTC by Yasir S Elhassan

Eur J Endocrinol. 2024 Aug 30;191(3):334-344. doi: 10.1093/ejendo/lvae106.

ABSTRACT

BACKGROUND: Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause of Cushing's syndrome. Individuals with PBMAH and glucose-dependent insulinotropic polypeptide (GIP)-dependent Cushing's syndrome due to ectopic expression of the GIP receptor (GIPR) typically harbor inactivating KDM1A sequence variants. Primary unilateral macronodular adrenal hyperplasia (PUMAH) with concomitant glucocorticoid and androgen excess has never been encountered or studied.

METHODS: We investigated a woman with a large, heterogeneous adrenal mass and severe adrenocorticotropic hormone-independent glucocorticoid and androgen excess, a biochemical presentation typically suggestive of adrenocortical carcinoma. The patient presented during pregnancy (22nd week of gestation) and reported an 18-month history of oligomenorrhea, hirsutism, and weight gain. We undertook an exploratory study with detailed histopathological and genetic analysis of the resected adrenal mass and leukocyte DNA collected from the patient and her parents.

RESULTS: Histopathology revealed benign macronodular adrenal hyperplasia. Imaging showed a persistently normal contralateral adrenal gland. Whole-exome sequencing of 4 representative nodules detected KDM1A germline variants, benign NM_001009999.3:c.136G > A:p.G46S, and likely pathogenic NM_001009999.3:exon6:c.865_866del:p.R289Dfs*7. Copy number variation analysis demonstrated an additional somatic loss of the KDM1A wild-type allele on chromosome 1p36.12 in all nodules. RNA sequencing of a representative nodule showed low/absent KDM1A expression and increased GIPR expression compared with 52 unilateral sporadic adenomas and 4 normal adrenal glands. Luteinizing hormone/chorionic gonadotropin receptor expression was normal. Sanger sequencing confirmed heterozygous KDM1A variants in both parents (father: p.R289Dfs*7 and mother: p.G46S) who showed no clinical features suggestive of glucocorticoid or androgen excess.

CONCLUSIONS: We investigated the first PUMAH associated with severe Cushing's syndrome and concomitant androgen excess, suggesting pathogenic mechanisms involving KDM1A.

PMID:39171930 | PMC:PMC11378072 | DOI:10.1093/ejendo/lvae106

Permalink for 'Demographic and Clinical Characteristics of Patients with Adrenal Incidentaloma from a Single Center in South India: A Retrospective Study'

Demographic and Clinical Characteristics of Patients with Adrenal Incidentaloma from a Single Center in South India: A Retrospective Study

Fetched: August 22nd, 2024, 2:00am UTC by Abhijeet B Jawanjal

Ann Afr Med. 2024 Oct 1;23(4):567-574. doi: 10.4103/aam.aam_212_23. Epub 2024 Aug 19.

ABSTRACT

CONTEXT: Adrenal incidentalomas (AIs) are relatively uncommon neoplasms in 2% of apparently healthy individuals requiring evaluation for functionality and malignancy.

AIM: We aimed to study the clinical, biochemical, and radiological profiles of patients presenting with AI and histopathological outcomes of those undergoing adrenalectomy. Materials and Methods: This retrospective study enrolled 62 AI patients attending a tertiary care center in South India between January 2016 and October 2023. Demographic details, radiological features, functionality, and histopathological data were analyzed.

RESULTS: Out of 62 patients, total masses evaluated were 65 indicating bilaterality in 3 patients. The female: male ratio was 1.69, with a median age of 55 years (interquartile range: 44-64 years). 45.1% of individuals were >60 years. The most common indication for imaging was pain abdomen in 43 (69.4%). The median size was 3.2 cm. Fifty-five (88.7%) were assessed for functionality and 27 (49.1%) were functional. Among the 62 individuals, 14 (20.2%) had hypercortisolism, 11 (15.9%) had pheochromocytoma, 5 (7.24%) had primary hyperaldosteronism (PA), and 4 (5.7%) had hyperandrogenism including plurihormonal in 7. A mass size of 3.2 cm was of great value in distinguishing functional tumors with a sensitivity of 72% and specificity of 66% with an area under the curve of 0.682. A total of 34 (54.8%) patients underwent adrenalectomy. On histopathological examination, Adenoma (44.1%) was the most common followed pheochromocytoma (26.5%), adrenal cysts (8.8%), and Myelolipoma (5.9%). Two (5.9%) incidentalomas were adrenocortical carcinoma (ACC). Eight (53.3%) adenomas were functional with 6 having hypercortisolism (including 1 with hyperandrogenism) and 2 with PA.

CONCLUSION: In our experience, the incidence of pheochromocytoma was second most common after adenoma. Since most functional tumors (60%) and all ACCs were â‰¥4 cm, a thorough biochemical evaluation for hormonal excess and evaluation for malignancy followed by surgery should be considered for lesions, especially â‰¥4 cm. Thus, we report the baseline demographic and clinical characteristics of patients with AI from a single center in South India.

PMID:39164941 | DOI:10.4103/aam.aam_212_23

The effect of adrenalectomy on overall survival in metastatic adrenocortical carcinoma

Fetched: August 21st, 2024, 2:00am UTC by Anis Assad

J Clin Endocrinol Metab. 2024 Aug 20:dgae571. doi: 10.1210/clinem/dgae571. Online ahead of print.

ABSTRACT

CONTEXT: Although complete surgical resection provides the only means of cure in adrenocortical carcinoma (ACC), the magnitude of the survival benefit of adrenalectomy in metastatic ACC (mACC) is unknown.

OBJECTIVE: To assess the effect of adrenalectomy on survival outcomes in patients with mACC in a real-world setting.

DESIGN AND SETTING: Patients with mACC were identified within the Surveillance, Epidemiology, and End Results database (SEER 2004-2020) and we tested for differences according to adrenalectomy status.

PATIENTS: Patients aged â‰¥18 years with metastatic ACC at initial presentation who were treated between 2004-2020.

INTERVENTION: Primary tumor resection status (Adrenalectomy vs no-adrenalectomy).

MAIN OUTCOME AND MEASURES: Kaplan-Meier plots, multivariable Cox regression models and landmark analyses were used. Sensitivity analyses focused on use of systemic therapy, contemporary (2012-2020) vs. historical (2004-2011), single vs. multiple metastatic sites and assessable specific solitary metastatic sites (lung only and liver only).

RESULTS: Of 543 patients with mACC, 194 (36%) underwent adrenalectomy. In multivariable analyses, adrenalectomy was associated with lower overall mortality without (hazard ratio [HR]: 0.39; p<0.001), as well as with three months' landmark analyses (HR: 0.57, p=0.002). The same association effect with three months' landmark analyses was recorded in patients exposed to systemic therapy (HR: 0.49, p<0.001), contemporary patients (HR: 0.57, p=0.004), historical patients (HR: 0.42 , p<0.001), and in those with lung only solitary metastasis (HR: 0.50, p=0.02). In contrast, no significant association was recorded in patients naÃ¯ve to systemic therapy (HR: 0.68, p=0.3), those with multiple metastatic sites (HR: 0.55, p=0.07) and those with liver only solitary metastasis (HR: 0.98, p=0.9).

CONCLUSIONS: The current results indicate a potential protective effect of adrenalectomy in mACC, particularly in patients exposed to systemic therapy and those with lung-only metastases.

PMID:39162017 | DOI:10.1210/clinem/dgae571

Permalink for 'A Database Tool Integrating Genomic and Pharmacologic Data from Adrenocortical Carcinoma (ACC) Cell Lines, PDX, and Patient Samples'

A Database Tool Integrating Genomic and Pharmacologic Data from Adrenocortical Carcinoma (ACC) Cell Lines, PDX, and Patient Samples

Fetched: August 21st, 2024, 2:00am UTC by Yashuhiro Arakawa

Cancer Res Commun. 2024 Sep 1;4(9):2384-2398. doi: 10.1158/2767-9764.CRC-24-0100.

ABSTRACT

Adrenocortical carcinoma (ACC) is a rare and highly heterogeneous disease with a notably poor prognosis due to significant challenges in diagnosis and treatment. Emphasizing on the importance of precision medicine, there is an increasing need for comprehensive genomic resources alongside well-developed experimental models to devise personalized therapeutic strategies. We present ACC_CellMinerCDB, a substantive genomic and drug sensitivity database (available at [https:] comprising ACC cell lines, patient-derived xenografts, surgical samples, and responses to more than 2,400 drugs examined by the NCI and National Center for Advancing Translational Sciences. This database exposes shared genomic pathways among ACC cell lines and surgical samples, thus authenticating the cell lines as research models. It also allows exploration of pertinent treatment markers such as MDR-1, SOAT1, MGMT, MMR, and SLFN11 and introduces the potential to repurpose agents like temozolomide for ACC therapy. ACC_CellMinerCDB provides the foundation for exploring larger preclinical ACC models.

SIGNIFICANCE: ACC_CellMinerCDB, a comprehensive database of cell lines, patient-derived xenografts, surgical samples, and drug responses, reveals shared genomic pathways and treatment-relevant markers in ACC. This resource offers insights into potential therapeutic targets and the opportunity to repurpose existing drugs for ACC therapy.

PMID:39162009 | PMC:PMC11389377 | DOI:10.1158/2767-9764.CRC-24-0100

Ex vivo MRI and histological comparison of the canine adrenal glands

Fetched: August 21st, 2024, 2:00am UTC by Olga AmorÃ³s CarafÃ

Vet Radiol Ultrasound. 2024 Aug 19. doi: 10.1111/vru.13425. Online ahead of print.

ABSTRACT

Cross-sectional imaging is widely used to characterize adrenal gland tumors in humans. In small animal veterinary medicine, while some studies have attempted to distinguish between types of adrenal gland neoplasia using CT, peer-reviewed studies investigating canine adrenal glands on MRI are scant. This prospective, pilot, single-center, method comparison, cadaveric study aimed to assess the agreement between ex vivo MRI findings and analogous histopathological findings of the adrenal glands in dogs. The adrenal glands of randomly selected dogs presented for necropsy were examined by MRI (n = 31). Additionally, five adrenal masses in dogs who underwent invasive adrenalectomy (including three adrenocortical carcinomas, one pheochromocytoma, and one adenoma) were imaged. Subsequently, gross pathology and histopathology of all the specimens were performed and correlated with the imaging findings. Adrenal gland lesions were identified on MRI with a sensitivity of 24%, a specificity of 100%, a positive predictive value of 100%, a negative predictive value of 31%, and an accuracy of 45%. The present study provides MRI features of multiple adrenal gland lesions that had never been described in dogs, including cortical hyperplasia, nodular fibrosis, hemorrhage, or multiple tumors, such as adenoma, carcinoma, and hemangiosarcoma. While MRI identified numerous adrenal gland lesions, a significant portion of those went undetected. Therefore, the absence of adrenal gland lesions on MRI does not exclude the possibility of histological lesions being present.

PMID:39160654 | DOI:10.1111/vru.13425

Loco-regional recurrence of adrenocortical carcinoma: A case report

Fetched: August 18th, 2024, 2:00am UTC by Bikash Chandra Sah

Int J Surg Case Rep. 2024 Sep;122:110095. doi: 10.1016/j.ijscr.2024.110095. Epub 2024 Jul 30.

ABSTRACT

INTRODUCTION: Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy with a high recurrence rate. Approximately half of the patients are asymptomatic, while others experience symptoms due to the tumor's size or hormone secretion. Ro resection if possible is the best option for treatment of primary as well as locoregional recurrent ACC.

CASE PRESENTATION: A 20-year-old female who previously underwent open left adrenalectomy for Stage III ACC presented with complaints of heaviness and vague discomfort in the left upper abdomen. Current hormonal assays were normal. Imaging revealed a lesion in the spleen suggestive of recurrence. She underwent elective surgery involving en bloc resection of the spleen, diaphragm, and associated structures. Postoperative recovery was uneventful, histopathology confirmed recurrence and subsequent PET-CT showed no recurrence. She is currently on mitotane and remains symptom-free with no signs of recurrence after initial surgery.

CLINICAL DISCUSSION: Complete resection (Ro) if possible, for recurrent and metastatic disease has been linked to long-term survival and offers significant palliative benefits, particularly in cases involving symptomatic steroid production.

CONCLUSION: ACC has a high frequency of local recurrence therefore management of recurrence should be considered from the initial diagnosis. Ro resection of recurrence is the best potential treatment. Follow-up protocols and improving integration between surgical, oncological, and supportive care departments are crucial for overcoming healthcare challenges in Nepal.

PMID:39151391 | PMC:PMC11375248 | DOI:10.1016/j.ijscr.2024.110095

Metastatic Adrenocortical Carcinoma to the Skin: A Case Report and Review of This Unusual Neoplasm

Fetched: August 15th, 2024, 2:00am UTC by Efrain Lee-Diaz

Am J Dermatopathol. 2024 Oct 1;46(10):696-699. doi: 10.1097/DAD.0000000000002816. Epub 2024 Aug 14.

ABSTRACT

Adrenocortical carcinoma is a very rare oncologic condition with poor prognosis that usually metastasizes to the lungs, liver, local lymph nodes, and peritoneum at initial presentation. However, skin metastasis is very uncommon and has rarely been reported even in advanced stages of the disease. We present a case of a 41-year-old man with a known history of adrenocortical carcinoma of the right adrenal gland that presented with an arm mass. The histopathologic sections showed a multinodular necrotic malignant neoplasm in dermis and subcutaneous fat composed of atypical epithelioid cells with ample granular cytoplasm and pleomorphic vesicular nuclei with frequent intranuclear inclusions and atypical mitoses. The immunohistochemical stains showed tumor cells that were strongly positive for synaptophysin and inhibin, only focally positive for Melan-A, and negative for AE1/AE3. The histopathologic features and the immunohistochemical profile confirmed the diagnosis of metastatic carcinoma consistent with adrenal cortical origin. The diagnosis can be difficult (especially when no clinical data are provided), and an immunohistochemical battery is often useful in distinguishing this tumor from other tumors with similar cytomorphological features.

PMID:39141753 | DOI:10.1097/DAD.0000000000002816

Characteristics of Adrenal Hemorrhage: A Single Clinic's Experience

Fetched: August 15th, 2024, 2:00am UTC by Siavash Åšwieczkowski-Feiz

Pol Przegl Chir. 2024 Apr 2;96(4):36-43. doi: 10.5604/01.3001.0054.4570.

ABSTRACT

PMID:39138988 | DOI:10.5604/01.3001.0054.4570

ADRENOCORTICAL CARCINOMA: AN ORPHAN MALIGNANCY: FROM THE PATIENT TO THE BENCH AND BACK

Fetched: August 14th, 2024, 2:00am UTC by Margaret E Wierman

Trans Am Clin Climatol Assoc. 2024;134:113-122.

ABSTRACT

PMID:39135585 | PMC:PMC11316896

From Nonfunctioning Adrenocortical Cancer to Biochemically Silent Paraganglioma Associated with SDHB Mutation: An Uncommon Presentation of a Patient with a Retroperitoneal Mass

Fetched: August 13th, 2024, 2:00am UTC by Izabella Freitas

Case Rep Endocrinol. 2024 Aug 2;2024:6664694. doi: 10.1155/2024/6664694. eCollection 2024.

ABSTRACT

PMID:39129823 | PMC:PMC11315972 | DOI:10.1155/2024/6664694

Development and validation of a liquid chromatography coupled to a diode array detector (LC-DAD) method for measuring mitotane (DDD) in plasma samples

Fetched: August 12th, 2024, 2:00am UTC by Anna Sylvia Ferrari Marques

Clinics (Sao Paulo). 2024 Aug 10;79:100470. doi: 10.1016/j.clinsp.2024.100470. eCollection 2024.

ABSTRACT

INTRODUCTION: Mitotane (o,p'-DDD) is the drug of choice for Adrenocortical Carcinomas (ACC) and its measurement in plasma is essential to control drug administration.

OBJECTIVE: To develop and validate a simple, reliable and straightforward method for mitotane determination in plasma samples.

PMID:39128398 | PMC:PMC11366885 | DOI:10.1016/j.clinsp.2024.100470

Differences in life expectancy of adrenocortical carcinoma patients vs. age- and sex-matched population controls

Fetched: August 12th, 2024, 2:00am UTC by Letizia Maria Ippolita Jannello

Int Urol Nephrol. 2024 Aug 12. doi: 10.1007/s11255-024-04180-9. Online ahead of print.

ABSTRACT

PURPOSE: To quantify to what extent the 5-year overall survival (OS) of adrenocortical carcinoma (ACC) patients differs from age- and sex-matched population-based controls, especially when stage is considered.

METHODS: We relied on the Surveillance, Epidemiology, and End Results database (2004-2020) to identify newly diagnosed (2004-2014) ACC patients. Subsequently, we compared OS between ACC patients relative to simulated age- and sex-matched controls (Monte Carlo simulation), according to Social Security Administration Life Tables (2004-2020).

RESULTS: Of all 742 ACC patients, 301 (41%) harbored localized stage, 173 (23%) locally advanced stage, and 268 (36%) metastatic stage. At 5-years follow-up, ACC patients' OS was 33%. After stratification for stage, the 5-years OS was 55 vs. 31 vs. 8% in localized, locally advanced, and metastatic stages, respectively. Conversely, after Monte Carlo simulation of age- and sex-matched controls, OS at five-years was 93% in the entire simulated cohort vs. 94% in the simulated localized cohort vs. 92 and 92% in locally advanced and metastatic stage, respectively. The resulting differences in OS between ACC patients and age- and sex-matched population-based controls were 60 vs. 39 vs. 61 vs. 84% respectively in the overall cohort vs. localized vs. locally advanced vs. metastatic stage.

CONCLUSION: The most pronounced life expectancy detriment (84%) was recorded in metastatic ACC followed by locally advanced ACC patients (61%). Unfortunately, even in patients with localized ACC, life expectancy was 39% lower than that of the general population. Therefore, regardless of stage, ACC diagnosis results in a very pronounced detriment in life expectancy relative to the general population.

PMID:39129040 | DOI:10.1007/s11255-024-04180-9

Adrenocortical carcinoma: selective internal radiation therapy and liver metastases

Fetched: August 8th, 2024, 2:00am UTC by Leo Baxendale-Smith

Endocr Oncol. 2024 Jul 8;4(1):e230041. doi: 10.1530/EO-23-0041. eCollection 2024 Jan 1.

ABSTRACT

PMID:39108463 | PMC:PMC11301532 | DOI:10.1530/EO-23-0041

Adrenocortical carcinoma: what you at least should know

Fetched: August 7th, 2024, 2:00am UTC by Charles de Ponthaud

Br J Surg. 2024 Aug 2;111(8):znae177. doi: 10.1093/bjs/znae177.

NO ABSTRACT

PMID:39107063 | DOI:10.1093/bjs/znae177

LncRNA ZFHX4-AS1 as a novel biomarker in adrenocortical carcinoma

Fetched: August 6th, 2024, 2:00am UTC by Guo Chen

Transl Androl Urol. 2024 Jul 31;13(7):1188-1205. doi: 10.21037/tau-23-649. Epub 2024 Jul 16.

ABSTRACT

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and highly aggressive malignant tumor. Currently, there is a lack of reliable prognostic markers in clinical practice. Extensive research has shown that long non-coding RNA (lncRNA) are critical factors in the initiation and progression of cancer, closely associated with early diagnosis and prognosis. Previous studies have identified that ZFHX4 antisense RNA 1 (ZFHX4-AS1) is aberrantly expressed in various cancers and is associated with poor outcomes. This study investigates whether ZFHX4-AS1 affects the prognosis of ACC patients and, if so, the potential mechanisms involved.

METHODS: In this study, utilizing four multi-center cohorts from The Cancer Genome Atlas (TCGA) program and Gene Expression Omnibus (GEO), we validated the prognostic capability of ZFHX4-AS1 in ACC patients through Kaplan-Meier survival analysis, cox regression models, and nomograms. Then, we explored the biological functions of ZFHX4-AS1 using gene set enrichment analysis (GSEA), competing endogenous RNA (ceRNA) networks, and analyses of somatic mutations and copy number variation (CNV). Finally, in vitro experiments were conducted to further validate the impact of ZFHX4-AS1 on proliferation and migration capabilities of ACC cell lines.

RESULTS: Survival analysis indicated that patients in the high ZFHX4-AS1 expression group of ACC had worse prognosis. Cox regression analyses suggested that ZFHX4-AS1 levels were independent risk factors for prognosis. Subsequently, we constructed nomograms based on clinical features and ZFHX4-AS1 levels, demonstrating good predictive performance under the time-dependent receiver operating characteristic (ROC) curve. Analysis based on somatic mutations and CNV revealed that CTNNB1 and 9p21.3-Del drove the expression of ZFHX4-AS1. Cell Counting Kit-8 (CCK-8), colony formation, and Transwell assays confirmed that knockdown of ZFHX4-AS1 inhibited proliferation and migration of ACC cells.

CONCLUSIONS: This study demonstrates that ZFHX4-AS1 has a reliable predictive value for the prognosis of ACC patients and is a promising biomarker.

PMID:39100837 | PMC:PMC11291411 | DOI:10.21037/tau-23-649

Papillary Thyroid Carcinoma, Cushing Disease, and Adrenocortical Carcinoma in a Patient with Li-Fraumeni Syndrome

Fetched: August 6th, 2024, 2:00am UTC by Jared G Friedman

AACE Clin Case Rep. 2024 Mar 28;10(4):127-131. doi: 10.1016/j.aace.2024.03.007. eCollection 2024 Jul-Aug.

ABSTRACT

BACKGROUND/OBJECTIVE: Li-Fraumeni syndrome (LFS) is an inherited sequence variant in TP53 characterized by the early onset of various core malignancies including adrenocortical carcinoma (ACC), sarcomas, breast cancer, leukemias, and central nervous system tumors. We present a case of a patient with LFS who developed endocrine neoplasms not classically seen in LFS in addition to developing ACC.

CASE REPORT: A 26-year-old nonbinary individual assigned female at birth with a history of LFS complicated by osteosarcoma of the jaw was incidentally found to have thyroid and sellar masses on surveillance magnetic resonance imaging. Fine-needle aspiration of thyroid mass confirmed papillary thyroid carcinoma, and the patient underwent total thyroidectomy. Pituitary workup was notable for laboratory test results consistent with adrenocorticotropic hormone-dependent hypercortisolism; the patient underwent resection of the pituitary lesion. The patient was subsequently noted on abdominal imaging to have a new left adrenal mass; they underwent left adrenalectomy with pathology consistent with ACC.

DISCUSSION: There is limited literature on the relationship between LFS and thyroid and pituitary neoplasms. Genetic testing has suggested that TP53 sequence variants may play a role in tumorigenesis in thyroid and pituitary neoplasms; however, most of the current literature is based on evidence of somatic rather than germline sequence variants.

CONCLUSION: This case highlights a patient with LFS with neoplasia of multiple endocrine organs including ACC, which is a classic finding, as well as papillary thyroid carcinoma and Cushing disease. Further investigation may be necessary to assess if patients with LFS are at a higher risk of various endocrine neoplasms in addition to the core malignancies classically described because this could affect future screening protocols.

PMID:39100628 | PMC:PMC11294748 | DOI:10.1016/j.aace.2024.03.007

Paraneoplastic Syndrome in Adrenocortical Carcinoma: The Unexpected Mime

Fetched: August 2nd, 2024, 2:00am UTC by Corina Nava Suarez

Cureus. 2024 Jun 30;16(6):e63534. doi: 10.7759/cureus.63534. eCollection 2024 Jun.

ABSTRACT

Adrenocortical carcinoma (ACC) is a malignancy of the adrenal cortex with a high morbidity and mortality. More than half of the cases are functional tumors. As different hormones can be co-secreted above physiologic levels, it causes a very broad variety of symptoms and makes differentiating from more common entities hard. Here we present a case of a patient with a newly diagnosed ACC who initially presented with acute pulmonary embolism and recurrent deep vein thromboses (DVT) in the setting of hypercortisolism. Imaging showed a left adrenal mass invading adjacent structures including a nonocclusive thrombus in the left renal vein. Intravenous anticoagulation and thrombectomy were initially performed, followed by removal of the tumor and adjacent metastatic disease. Pathology confirmed ACC. The patient underwent left adrenalectomy, left nephrectomy, splenectomy, distal pancreatectomy, and caval thrombectomy with inferior vena cava (IVC) filter placement. Intravenous anticoagulation and glucocorticoid replacement were also administered as part of the treatment plan. Unfortunately, the patient had multiple episodes of bleeding and thrombosis and was eventually discharged to hospice care. DVT in the setting of ACC can be caused by increased hypercoagulability from hypercortisolism, direct venous thrombosis, or vascular invasion. Thrombosis, especially in the inferior vena cava, has been associated with poor prognosis and survival rates. Clinicians should be aware of this rare complication given its immediate therapeutic repercussions and prognostic value.

PMID:39086789 | PMC:PMC11288974 | DOI:10.7759/cureus.63534

Transformation of a Benign Adrenocortical Adenoma to a Metastatic Adrenocortical Carcinoma Is Rare But It Happens

Fetched: August 1st, 2024, 2:00am UTC by Anna Angelousi

JCEM Case Rep. 2024 Jul 30;2(8):luae131. doi: 10.1210/jcemcr/luae131. eCollection 2024 Aug.

ABSTRACT

The transformation of an adrenocortical adenoma (ACA) to an adrenocortical carcinoma (ACC) is extremely rare. Current guidelines suggest against further imaging studies and follow-up in patients with nonfunctional adrenal incidentalomas (NFAIs) with benign imaging characteristics. Herein, we present a 64-year-old male patient diagnosed initially with a NFAI of 3 cm in size with imaging characteristics consistent with an ACA. However, 13 years after initial diagnosis, this apparent ACA developed into a high-grade cortisol and androgen-secreting ACC with synchronous metastases. The literature review revealed a further 9 case reports of adrenal incidentalomas initially characterized as ACA that subsequently developed into ACC within a period ranging from 1 to 10 years. The pathogenesis of transformation of an initially denoted ACA to ACC is not fully delineated, although the existing literature focuses on the preexisting or changing genetic background of these lesions, highlighting the need to develop robust prognostic markers to identify patients at risk and individualize the follow-up of these unique cases.

PMID:39081696 | PMC:PMC11288369 | DOI:10.1210/jcemcr/luae131

Prognostic value of fibrinogen change value in adrenocortical carcinoma patients

Fetched: July 31st, 2024, 2:00am UTC by Chengquan Ma

Discov Oncol. 2024 Jul 30;15(1):320. doi: 10.1007/s12672-024-01197-5.

ABSTRACT

PURPOSE: The aim was to explore the preoperative and postoperative fibrinogen changes value (FCV) as a prognosis biomarker for in patients with adrenocortical carcinoma (ACC).

METHODS: We identified 42 patients with ACC and 190 patients with adrenal adenoma (AA) who underwent surgery at our institution between 2015 and 2023. Preoperative fibrinogen, postoperative fibrinogen and follow-up information of the patients were recorded and analysed. The relationship between FCV and overall survival (OS)/ relapse-free survival (RFS) was evaluated.

RESULTS: The mean level of preoperative and postoperative fibrinogen for ACC were 4.00 Â± 1.64 g/L and 2.75 Â± 0.59 g/L, respectively (p < 0.001). The mean level of preoperative and postoperative fibrinogen for AA were 2.79 Â± 0.59 g/L and 2.71 Â± 0.58 g/L, respectively (p = 0.144). In ACC, the lower FCV (â‰¤ 1.25 g/L) showed a significantly poorer RFS than the higher (> 1.25 g/L) (p = 0.007); however, the lower FCV (â‰¤ 1.25 g/L) showed no poorer OS than the higher (> 1.25 g/L) (p = 0.243). On multivariate survival analyses, FCV remained a predictor of RFS (HR 3.138).

CONCLUSION: According to the data in this study, it can be said that FCV is correlated with prognosis of ACC. The FCV might be a new biomarker for predicting the RFS of ACC.

PMID:39080085 | PMC:PMC11289202 | DOI:10.1007/s12672-024-01197-5

Ocular adnexal sebaceous carcinoma in a patient with Li-Fraumeni syndrome

Fetched: July 30th, 2024, 2:00am UTC by Chia W Hsu

Orbit. 2024 Jul 29:1-5. doi: 10.1080/01676830.2024.2382268. Online ahead of print.

ABSTRACT

Li-Fraumeni syndrome (LFS) is caused by a pathogenic germline variant at the TP53 locus and is associated with an increased predisposition to a variety of cancers. The neoplasms most frequently associated with LFS are sarcomas, breast cancer, brain tumors, and adrenocortical carcinomas. In this case report, we present a 43-year-old male diagnosed with an ocular adnexal sebaceous carcinoma of the right upper eyelid who was confirmed to have LFS with subsequent genetic testing. The mutational profile of both the patient's genetic screen and tumor sequencing were congruent, demonstrating the same pathogenic loss-of-function TP53 variant. This case report highlights the importance of pursuing genetic testing in patients with a history of multiple tumor types, particularly those with uncommon diagnoses. In this case, confirmation of LFS had important implications for personalized patient care, including identification of contraindicated treatment interventions and the imaging modalities necessary for vigilant follow-up screening.

PMID:39072610 | DOI:10.1080/01676830.2024.2382268

Phase II basket trial of Dual Anti-CTLA-4 and Anti-PD-1 blockade in Rare Tumors (DART) SWOG S1609: adrenocortical carcinoma cohort

Fetched: July 29th, 2024, 2:00am UTC by Sandip P Patel

J Immunother Cancer. 2024 Jul 27;12(7):e009074. doi: 10.1136/jitc-2024-009074.

ABSTRACT

OBJECTIVES: Multiple common cancers benefit from immunotherapy; however, less is known about efficacy in rare tumors. We report the results of the adrenocortical carcinoma cohort of NCI/SWOG S1609 Dual Anti-CTLA-4 and Anti-PD-1 blockade in Rare Tumors.

DESIGN/SETTING: A prospective, phase 2 clinical trial of ipilimumab plus nivolumab was conducted by the SWOG Early Therapeutics and Rare Cancers Committee for multiple rare tumor cohorts across >1,000 National Clinical Trial Network sites.

PARTICIPANTS: 21 eligible patients were registered. Median age was 53 years (range 26-69); 16 (76%) were women.

INTERVENTIONS: Ipilimumab 1 mg/kg intravenously every 6 weeks with nivolumab 240 mg intravenously every 2 weeks was administered until disease progression, symptomatic deterioration, treatment delay for any reason >56 days, unacceptable or immune-related toxicity with inability to decrease prednisone to <10 mg daily, or per patient request.

MAIN OUTCOME MEASURES: The primary endpoint was the overall response rate (ORR) (RECIST V.1.1). Secondary endpoints include clinical benefit rate (CBR) (includes stable disease (SD)>6 months), progression-free survival (PFS), overall survival (OS), and toxicity. Immune-related outcomes included immune ORR (iORR), immune CBR (iCBR), and immune PFS (iPFS). A two-stage design was used assuming: null=5% alternative=30%, n=6 in the first stage, 16 max, one-sided alpha=13%.

RESULTS: The median number of prior therapy lines was 2 (range: 1-9). 3 of 21 patients attained confirmed partial response (PR) (ORR=14%). In addition, one patient had an unconfirmed PR; one, stable disease (SD)>6 months; one, immune-related RECIST (iRECIST) PR (iPR); and one patient attained iSD>6 months: clinical benefit rate (response or SD>6 months)=5/21 (24%), iORR=4/21 (19%), iCBR=7/21 (33%). The 6-month PFS was 24%; 6-month iPFS, 33%. The PFS for patients (N=7) with iRECIST clinical benefit were 57, 52, 18, 15, 13, 7, and 7 months. The 6-month OS was 76%; the median OS, was 15.8 months. The most common toxicities were fatigue (62%) and rash (38%), and the most common grade 3/4 immune-related adverse events were hepatic dysfunction (9.5%) and adrenal insufficiency (9.5%). Treatment-related adverse events leading to discontinuation of therapy in four patients (21%). There were no grade 5 adverse events.

CONCLUSIONS: Ipilimumab plus nivolumab is active in refractory metastatic adrenocortical cancer meeting the primary endpoint of the study, with a 19% iORR and 33% iCBR (includes SD/iSD>6 months) and with the longest PFS/iPFS of 52 and 57 months.

TRIAL REGISTRATION NUMBER: NCT02834013 (registered 15 July, 2016; [https:]

PMID:39067873 | PMC:PMC11284838 | DOI:10.1136/jitc-2024-009074

Systemic Management of Advanced Adrenocortical Carcinoma

Fetched: July 29th, 2024, 2:00am UTC by Jeffery S Russell

Curr Treat Options Oncol. 2024 Aug;25(8):1063-1072. doi: 10.1007/s11864-024-01249-6. Epub 2024 Jul 27.

ABSTRACT

Adrenocortical cancer (ACC) is a rare and aggressive disease. Surgery has traditionally been the primary treatment for locally advanced disease with ongoing controversy around the optimal neoadjuvant and adjuvant treatment options. Unfortunately, local recurrence and the eventual development of metastatic disease is common and five-year survival rates are poor. While many trials have evaluated novel systemic agents to treat advanced adrenocortical cancer, only a few drugs have demonstrated any response at all. To date, only one drug, mitotane, is approved in the US for ACC and no regimen has clearly shown an increase in overall survival. In advanced metastatic or unresectable disease, data supports the first line regimen of EDP chemotherapy + mitotane as the primary treatment modality. In the second line, while data is limited, we would recommend consideration of immunotherapy using a PD(L)1 agent combined with a TKI/VEGF inhibitor or combination immunotherapy with PD1/CTLA-4 drugs. In all cases, we always prefer a clinical trial as available. This article reviews data from multiple studies evaluating novel systemic agents against ACC and discusses current systemic therapy combinations and ongoing clinical trials.

PMID:39066856 | DOI:10.1007/s11864-024-01249-6

Permalink for 'Assessment of the diagnostic efficacy of radiological and functional evaluation of primary adrenal mass and its' surgical outcomes'

Assessment of the diagnostic efficacy of radiological and functional evaluation of primary adrenal mass and its' surgical outcomes

Fetched: July 27th, 2024, 2:00am UTC by Yash Manharlal Tilala

Urologia. 2024 Jul 25:3915603241259881. doi: 10.1177/03915603241259881. Online ahead of print.

ABSTRACT

INTRODUCTION: Objective of this study was to assess the diagnostic efficacy of the most commonly used radiological evaluation in form of contrast enhanced computed tomography of abdomen with adrenal protocol, basic functional evaluation and surgical outcomes of primary adrenal masses.

MATERIAL AND METHODS: We have retrospectively analysed the institutional records of 108, patients admitted from August 2017 to September 2023, who had underwent surgical intervention for their adrenal mass after thorough evaluation and stabilization.

RESULTS: Flank pain was the most common symptoms in 44 (40.74%) patients. Non-functional adrenal adenoma was found in 36 (33.33%) patients. Pheochromocytoma was the most the common functional adrenal mass found in 24 (22.22%) patients. CECT abdomen had suggested features of malignancy in 16(14.81%) patients. In final histopathological report 26(24.07%) patients had pheochromocytoma and 12 (11.11%) patients had adrenocortical carcinoma. CECT abdomen had sensitivity of 75%, specificity of 95.6%. Plasma free metanephrines and normetanephrine analysis had shown sensitivity of 90%, specificity of 92.86%, aldosterone to renin ratio had sensitivity of 92%, specificity of 100%. Sensitivity and specificity of the low-dose dexamethasone suppression test and plasma dehydroepiandrosterone was 100% in our study. Eighty patients (74.07%) were operated with laparoscopic adrenalectomy, 20 (18.52%) patients with open adrenalectomy. Eight patients (7.41%) were converted from laparoscopic to open. Laparoscopic approach had significantly lesser mean operating time, lesser blood loss, lesser hospitalization and lesser post-operative complications.

CONCLUSION: Radiological analysis and functional analysis has shown good sensitivity and high specificity. Laparoscopic approach has advantage of lesser operative time, lesser hospitalization and lesser post-operative complications.

PMID:39051607 | DOI:10.1177/03915603241259881

Permalink for 'Unveiling the Significance of NCAP Family Genes in Adrenocortical Carcinoma and Adenoma Pathogenesis: A Molecular Bioinformatics Exploration'

Unveiling the Significance of NCAP Family Genes in Adrenocortical Carcinoma and Adenoma Pathogenesis: A Molecular Bioinformatics Exploration

Fetched: July 25th, 2024, 2:00am UTC by Mahshid Arastonejad

Cancer Inform. 2024 Jun 23;23:11769351241262211. doi: 10.1177/11769351241262211. eCollection 2024.

ABSTRACT

OBJECTIVES: Adrenocortical carcinoma (ACC), a rare and aggressive adrenal cortex cancer, poses significant challenges due to high mortality, poor prognosis, and early post-surgery recurrence. Variability in survival across ACC stages emphasizes the need to uncover its molecular underpinnings. Adrenocortical adenoma, a benign tumor, adds to diagnostic challenges, highlighting the necessity for molecular insights. The Non-SMC Associated Condensin Complex (NCAP) gene family, recognized for roles in chromosomal structure and cell cycle control. This study focuses on evaluating NCAP gene functions and importance in ACC through gene expression profiling to identify diagnostic and therapeutic targets.

METHODS: Microarray datasets from ACC patients, obtained from the Gene Expression Omnibus database, were normalized to eliminate batch effects. Differential expression analysis of NCAP family genes, facilitated by the GEPIA2 database, included survival and pathological stage evaluations. A Protein-Protein Interaction network was constructed using GeneMANIA, and additional insights were gained through Gene Ontology enrichment analysis, correlation analysis, and ROC curve analysis.

RESULTS: ACC samples exhibited elevated levels of NCAPG, NCAPG2, and NCAPH compared to normal and adenoma samples. Increased expression of these genes correlated with poor overall survival, particularly in advanced disease stages. The Protein-Protein Interaction network highlighted interactions with related proteins, and Gene Ontology enrichment analysis demonstrated their involvement in chromosomal structure and control. Differentially expressed NCAP genes showed positive associations, and ROC curve analysis indicated their high discriminatory power in identifying ACC from adenoma and normal samples.

CONCLUSION: The study emphasizes the potential importance of NCAPG, NCAPG2, and NCAPH in ACC, suggesting roles in tumor aggressiveness and diagnostic relevance. These genes could serve as therapeutic targets and markers for ACC, but further exploration into their molecular activities and validation studies is imperative to fully harness their diagnostic and therapeutic potential, advancing precision medicine approaches against this rare but lethal malignancy.

PMID:39045040 | PMC:PMC11265250 | DOI:10.1177/11769351241262211

Clinical treatment and prognosis of adrenocortical carcinoma with venous tumor thrombus

Fetched: July 24th, 2024, 2:00am UTC by Shuai Liu

Beijing Da Xue Xue Bao Yi Xue Ban. 2024 Dec 18;56(4):624-630. doi: 10.19723/j.issn.1671-167X.2024.04.013.

ABSTRACT

OBJECTIVE: To analyze the clinicopathological features, prognostic value and surgical treatment experience in patients with adrenocortical carcinoma with venous tumor thrombus.

METHODS: We collected relevant data of the patients with adrenocortical carcinoma who had undergone surgery in Peking University Third Hospital from 2018 to 2023. The patients were divided into venous tumor thrombus group and non-tumor thrombus group. The Wilcoxon rank sum test was used to compare the quantitative variables. The chi-squared test and Fisher's exact test were used to compare the categorical variables. The Kaplan-Meier method was used to estimate the survival rate.

RESULTS: A total of 27 patients with adrenocortical carcinoma were included, of whom 11 cases (40.7%) had venous tumor thrombus. In the patients with venous tumor thrombus, 8 patients were female and 3 were male. The median age was 49 (36, 58) years. The median body mass index was 26.0 (24.1, 30.4) kg/m². Seven patients presented with symptoms at their initial visit. Six patients had a history of hypertension. Elevated levels of cortisol were observed in 2 cases. Three tumors were found on the left side, while 8 were found on the right side. Median tumor diameter was 9.4 (6.5, 12.5) cm. On the left, there was a case of tumor thrombus limited to the central vein of the left adrenal gland without invasion into the left renal vein, and two cases of tumor thrombus growth extending into the inferior vena cava below the liver. One case of tumor thrombus on the right adrenal central vein did not invade the inferior vena cava. Four cases of tumor thrombus invaded the inferior vena cava below the liver and three cases extended to the posterior of the liver. Ten patients were in European Network for the Study of Adrenal Tumors (ENSAT) stage â…¢ and one was in ENSAT stage â…£. Open surgery was performed in 6 cases, laparoscopic surgery alone in 4 cases and robot-assisted laparoscopic surgery in 1 case. Two patients underwent ipsilateral kidney resection. Median operative time was 332 (261, 440) min. Median intraoperative bleeding was 900 (700, 2 200) mL. Median hospital stay was 9 (5, 10) days. Median survival time for the patients with tumor thrombus was 24.0 months and median time to recurrence was 7.0 months. The median survival and recurrence time of 16 patients without tumor thrombus were not reached. The patients with tumor thrombus had worse 3-year overall survival (OS) rate (40.9% vs. 71.4%; Log-rank, P=0.038) and 2-year recurrence-free survival (RFS) (9.1% vs.53.7%; Log-rank, P=0.015) rates compared with the patients with non-tumor thrombus.

CONCLUSION: Patients with adrenocortical carcinoma with venous tumor thrombus have poor prognosis. Different adrenal tumor resections and venous tumor thrombus removal procedures based on different tumor thrombus locations are safe and effective in treating this disease.

PMID:39041556 | PMC:PMC11284474 | DOI:10.19723/j.issn.1671-167X.2024.04.013

Ante Situm Liver Resection for Tumors Invading the Inferior Vena Cava Hepatic Vein Confluence

Fetched: July 23rd, 2024, 2:00am UTC by Pietro Addeo

Ann Surg Oncol. 2024 Jul 22. doi: 10.1245/s10434-024-15849-x. Online ahead of print.

ABSTRACT

BACKGROUND: Liver malignancy invading the retrohepatic inferior vena cava beyond the cavo-hepatic vein venous confluence can be resected by an ante situm technique first described by Hannoun et al.¹ In this approach, a major hepatectomy is performed and the hepatic veins are sectioned to allow the inferior vena cava reconstruction while the liver is cold perfused and the liver remains within the abdominal cavity. The hepatic vein is then reimplanted on the reconstructed inferior vena cava in "a liver autotransplantation fashion."

PATIENT AND METHODS: The patient was a 66-year-old with a recurrent adrenocortical carcinoma cancer invading the right liver and the retrohepatic inferior vena cava with intraluminal thrombus extending beyond to the hepatic vein confluence. A right hepatectomy extended to segment 1 and the retrohepatic inferior vena cava was planned because of the intracaval tumoral thrombus and the infiltration of the right liver. The future liver remnant (FLR) (646 cc) to total liver volume (1526 cc) ratios was 42% while the FLR to patient weight ratio was 0.9%.

RESULTS: The parenchymal liver transection was performed under a total vascular exclusion, venovenous bypass, and hypothermic perfusion of the left liver.² The common trunk of the left and middle hepatic veins was sectioned, allowing the liver to be rotated toward the left. Vena cava reconstruction was achieved by a ringed Gore-Tex prosthesis, with reimplantation of the left and middle hepatic veins directly over the prosthesis. Surgery lasted 580 min, total duration of venovenous bypass and liver vascular exclusion was 143 min and 140 min, respectively. Blood loss was 2 liters and 8 red blood cell (RBC) units were transfused. The patient spent 5 days in the ICU, liver function tests normalized by postoperative day 8 and patient was discharged home on postoperative day 20; 1 year later, the patient is alive and disease free under mitotane treatment.

CONCLUSIONS: The ante situm technique represents a safe surgical option for complex liver resection for malignancy involving the cavo-hepatic venous confluence. Compared with the ex situ liver resection, this technique allows liver remnant outflow reconstruction to be performed while the liver is cold perfused within the abdominal cavity with an intact hepatic pedicle.

PMID:39037524 | DOI:10.1245/s10434-024-15849-x

A review of mitotane in the management of adrenocortical cancer

Fetched: July 23rd, 2024, 2:00am UTC by Jaydira Del Rivero

Oncologist. 2024 Jul 22:oyae084. doi: 10.1093/oncolo/oyae084. Online ahead of print.

ABSTRACT

IMPORTANCE: Mitotane (Lysodren, o,p'-DDD [1-(o-chlorophenyl)-1-(p-chlorophenyl)-2,2-dichloroethane)] is currently the only United States Food and Drug Administration and European Medicines Agency-approved product for the treatment of adrenocortical carcinoma.

OBSERVATIONS: Mitotane is challenging to administer; however, its toxicities (specifically adrenal insufficiency) are well known, and the management of adverse consequences has established approaches. While often viewed through the prism of a cytotoxic agent, it can also interfere with hormone production making it a valuable asset in managing functional ACC. A recently completed prospective trial has shed some light on its use in the adjuvant setting, but further clarity is needed. Many think mitotane has a role in the advanced or metastatic setting, although prospective data are lacking and retrospective analyses are often difficult to interpret.

CONCLUSIONS AND RELEVANCE: When used carefully and thoughtfully, especially in patients with hormonal excess, mitotane is an important component of the treatment armamentarium for ACC.

PMID:39037424 | DOI:10.1093/oncolo/oyae084

Permalink for 'Precocious puberty and other endocrine disorders during mitotane treatment for paediatric adrenocortical carcinoma - case series and literature review'

Precocious puberty and other endocrine disorders during mitotane treatment for paediatric adrenocortical carcinoma - case series and literature review

Fetched: July 20th, 2024, 2:00am UTC by ElÅ¼bieta MoszczyÅ„ska

Pediatr Endocrinol Diabetes Metab. 2024;30(1):14-28. doi: 10.5114/pedm.2023.133315.

ABSTRACT

INTRODUCTION: Adrenocortical carcinoma (ACC) is rare and an aggressive tumour. Mitotane is the mainstay adjuvant drug in treating ACC. The study aimed to describe patients diagnosed with precocious puberty (PP) and other endocrinological complications during mitotane therapy.

MATERIAL AND METHODS: This retrospective study enrolled 4 patients with ACC treated with mitotane therapy complicated by PP. We analysed clinical manifestations, radiological, histopathological findings, and hormonal results.

RESULTS: The median age at the diagnosis of ACC was 1.5 years. All patients were treated with surgery and mitotane, accompanied by chemotherapy regimens in 2 cases. The median time from surgery to the initiation of mitotane therapy was 26 days. During mitotane treatment, PP was confirmed based on symptoms, and hormonal and imaging tests. In one patient, incomplete peripheral PP was followed by central PP. The median time from the therapy initiation to the first manifestations of PP was 4 months. Additionally, due to mitotane-induced adrenal insufficiency, patients required a supraphysiological dose of hydrocortisone (HC), and in one patient, mineralocorticoid (MC) replacement with fludrocortisone was necessary. In 2 patients, hypothyroidism was diagnosed. All patients presented neurological symptoms of varying expression, which were more severe in younger children.

CONCLUSIONS: The side effects of using mitotane should be recognized quickly and adequately treated. In prepubertal children, PP could be a complication of therapy. The need to use supraphysiological doses of HC, sometimes with MC, should be highlighted. Some patients require levothyroxine replacement therapy. The neurotoxicity of mitotane is a significant clinical problem.

PMID:39026475 | PMC:PMC11037260 | DOI:10.5114/pedm.2023.133315

Adrenal cortical carcinoma: Paediatric aspects - literature review

Fetched: July 20th, 2024, 2:00am UTC by Patrycja Dasiewicz

Pediatr Endocrinol Diabetes Metab. 2024;30(2):81-90. doi: 10.5114/pedm.2024.139271.

ABSTRACT

INTRODUCTION: Adrenocortical carcinoma (ACC) is a rare malignancy in children. Because of this, each patient with suspected ACC requires individualised management, which should be determined at a meeting of a team of multidisciplinary experts in the field.

AIM OF THE STUDY: To summarise data on symptoms, genetic predisposition, and diagnostic procedures for ACC in children.

MATERIAL AND METHODS: Papers were searched in the PubMed database to identify published randomised clinical trials, reviews, systematic reviews, meta-analyses, and case reports.

RESULTS: Most cases of ACC in children occur under the age of 5 years. The most common presenting symptom in 60-80% of paediatric patients is rapidly progressive virilisation. Diagnostics are based on laboratory and imaging evaluation. The mainstay of treatment is surgery, with laparotomy being the preferred method of surgery. Diagnosis is based on histological examination of surgically removed tissue. The Wieneke index is most commonly used in paediatric practice. However, some cases are still classified as "indeterminate histology". Predisposing genetic factors are found in most children with ACC, most commonly a mutation of the TP53 gene.

CONCLUSIONS: Patients should be diagnosed in large clinical centres with experience in this field. The treatment strategy should be individualised. Genetic testing for TP53 gene mutations is indicated in patients with ACC.

PMID:39026485 | PMC:PMC11249794 | DOI:10.5114/pedm.2024.139271

From Adenoma to Carcinoma: the Unexpected Evolution of an Apparently Stable Adrenal Lesion

Fetched: July 19th, 2024, 2:00am UTC by Giacomo Cristofolini

Endocr Metab Immune Disord Drug Targets. 2024 Jul 15. doi: 10.2174/0118715303323057240621055000. Online ahead of print.

ABSTRACT

BACKGROUND: There is a lack of solid long-term evidence with respect to the management over time of adrenal incidentalomas that miss clearly benign radiological features. We present the case of a 75-year-old man with a non-secreting adrenal mass, apparently stable in size (14 mm) and unchanged in features for 2 years, but subsequently diagnosed as adrenal carcinoma.

CASE REPORT: The patient was referred to Grande Ospedale Metropolitano Niguarda in August 2022 due to the presence of a large lesion in the left adrenal site. In 2017, a 14 mm, 20 HU, round, regular-edged lesion was detected at a CT scan without contrast medium. Over the next two years, the patient was re-evaluated every 6 months with follow-up CT scans with no apparent densitometric or dimensional changes in the known lesion. In September 2022, 3 years after the last CT scan, the patient was hospitalised for pneumonia. An abdominal CT scan acquired during the hospitalisation showed an increase of the lesion to 14.5x10x12 cm. The patient subsequently underwent open nephrosurrenectomy, and histological examination confirmed the presence of an adrenal carcinoma (proliferation index 5%, Weiss score 7). No adjuvant therapy was administered, and the last CT scan in December 2022 was negative for the recurrence of the disease.

CONCLUSION: Adrenal carcinoma usually presents as a clearly malignant lesion with rapid growth and a marked tendency to metastasise. This case highlights how an adrenal adenoma with indeterminate features is worthy of follow-up over time despite its apparent dimensional and radiological stability [1].

PMID:39021177 | DOI:10.2174/0118715303323057240621055000

An ominous cause of hirsutism: Adrenocortical carcinoma

Fetched: July 18th, 2024, 2:00am UTC by Pankaj Singhania

Indian J Cancer. 2024 Jul 13. doi: 10.4103/ijc.ijc_86_22. Online ahead of print.

NO ABSTRACT

PMID:39016253 | DOI:10.4103/ijc.ijc_86_22

A comprehensive pan-cancer analysis revealing SPAG6 as a novel diagnostic, prognostic and immunological biomarker in tumor

Fetched: July 18th, 2024, 2:00am UTC by Xiaofei Li

Gland Surg. 2024 Jun 30;13(6):999-1015. doi: 10.21037/gs-24-157. Epub 2024 Jun 27.

ABSTRACT

BACKGROUND: There have been studies on the role of sperm-associated antigen 6 (SPAG6) in cytoskeleton formation and growth cone stability, but it is also unknown how spag6 affect tumor growth and development. The aim of this study was to clarify the role of SPAG6 in pan-cancer, with some findings about thyroid carcinoma (THCA) validated through experiments.

METHODS: We examined the role of SPAG6 in pan-cancer, with the data being collected from databases. Further analysis was conducted to assess its correlations with prognosis, gene heterogeneity, stemness, and tumor immunity. The interacting proteins of SPAG6 were also identified, and gene ontology enrichment analysis was performed to determine its biological function. We preliminarily confirmed the role of SPAG6 via in vitro experiments and immunofluorescence staining.

RESULTS: This study found that SPAG6 expression was differentially expressed in cancers and at various tumor stages and grades. In stomach and esophageal carcinoma (STES), stomach adenocarcinoma (STAD), kidney renal clear cell carcinoma (KIRC), lung squamous cell carcinoma (LUSC), and adrenocortical carcinoma (ACC), SPAG6 expression was correlated with gender. SPAG6 expression was also found to be correlated with prognostic value, with low expression being associated with poor prognosis. Furthermore, SPAG6 expression was positively linked with immune-related cells in HNSC, chemokine receptors in LUSC, and immune checkpoint genes in THCA. Furthermore, SPAG6 overexpression suppressed the malignant phenotypes of THCA cells, manifested by slower proliferation and decreased migration. The different SPAG6 expression in THCA led to different malignant phenotypes, which are involved in the upregulation of DNA repair, MYC targets, peroxisome, and G2M checkpoint.

CONCLUSIONS: SPAG6 plays a significant role as an oncogene and can be used as a marker to predict the prognosis of cancer. SPAG6 influences both the tumor immune infiltration and microenvironment, making it a promising immunotherapeutic target for tumor therapy.

PMID:39015705 | PMC:PMC11247597 | DOI:10.21037/gs-24-157

Virilizing adrenocortical carcinoma in a female child of Li-Fraumeni syndrome

Fetched: July 17th, 2024, 2:00am UTC by K V Vishnu Sankar

Indian J Pathol Microbiol. 2024 Jul 13. doi: 10.4103/ijpm.ijpm_906_23. Online ahead of print.

ABSTRACT

Adrenocortical carcinoma is a rare malignancy and even rarer in infancy. Most of these tumors in the pediatric age group are hormonally active and predominantly present with virilization. We report a case of a 1-year-3-month-old female child presenting with virilization. She presented with hypertension, hypertrichosis, clitoromegaly (virilization), and elevation of plasma testosterone and dehydroepiandrosterone. A discussion of this case and a review of the literature on this entity are presented.

PMID:39011620 | DOI:10.4103/ijpm.ijpm_906_23

ACTH-producing adrenocortical carcinoma: an exceedingly rare diagnosis

Fetched: July 15th, 2024, 2:00am UTC by Miguel Saraiva

J Egypt Natl Canc Inst. 2024 Jul 15;36(1):24. doi: 10.1186/s43046-024-00229-z.

ABSTRACT

BACKGROUND: Adrenocortical carcinoma is a very rare endocrinopathy that has a poor prognosis and is frequently associated with ACTH-independent Cushing's syndrome. Despite having an adrenocortical carcinoma, our patient surprisingly had an ACTH-dependent Cushing's syndrome.

CASE REPORT: A 26-year-old female presented with Cushing's syndrome and an abdominal mass. Imaging studies revealed an adrenal mass consistent with a high-grade malignancy. Laboratory workup showed hypercortisolism, hyperandrogenism, and hypokalemia with normal levels of metanephrines. Unexpectedly, her ACTH levels were remarkably elevated. The pathological analysis of a tumor sample was conclusive for adrenocortical carcinoma with immunopositivity for ACTH.

CONCLUSIONS: Our patient suffered from an adrenocortical carcinoma that was ectopically producing ACTH. This case emphasizes that physicians should have a broad-minded approach when evaluating cases of rare endocrine malignancies.

PMID:39004684 | DOI:10.1186/s43046-024-00229-z

A pan-cancer analysis unveiling the function of NR4A family genes in tumor immune microenvironment, prognosis, and drug response

Fetched: July 9th, 2024, 2:00am UTC by Seong-Woo Park

Genes Genomics. 2024 Aug;46(8):977-990. doi: 10.1007/s13258-024-01539-1. Epub 2024 Jul 8.

ABSTRACT

BACKGROUND: NR4A family genes play crucial roles in cancers. However, the role of NR4A family genes in cancers remains paradoxical as they promote or suppress tumorigenesis.

OBJECTIVE: We aimed to conduct comprehensive analyses of the association between the expression of NR4A family genes and tumor microenvironment (TME) based on bioinformatics methods.

METHODS: We collected RNA-seq data from 33 cancer types and 20 normal tissue sites from the TCGA and GTEx databases. Expression patterns of NR4A family genes and their associations with DNA methylation, miRNA, overall survival, drug responses, and tumor microenvironment were investigated.

RESULTS: Significant downregulation of all NR4A family genes was observed in 15 cancer types. DNA promoter methylation and expression of NR4A family genes were negatively correlated in five cancers. The expression of 10 miRNAs targeting NR4A family genes was negatively correlated with the expression of NR4A family genes. High expression of all NR4A family genes was associated with poor prognosis in stomach adenocarcinoma and increased expressions of NR4A2 and NR4A3 were associated with poor prognosis in adrenocortical carcinoma. In addition, we found an elevated expression of NR4A2, which enhances the response to various chemotherapeutic drugs, whereas NR4A3 decreases drug sensitivity. Interestingly, in breast cancer, NR4A3 was significantly associated with C2 (IFN-Î³ dominant), C3 (inflammatory), and C6 (TGF-Î² dominant) immune subtypes and infiltrated immune cell types, implying both oncogenic and tumor-suppressive functions of NR4A3 in breast cancer.

CONCLUSION: The NR4A family genes have the potential to serve as a diagnostic, prognostic, and immunological marker of human cancers.

PMID:38976216 | DOI:10.1007/s13258-024-01539-1

Permalink for 'Inflammation-based scores in a large cohort of adrenocortical carcinoma and adrenocortical adenoma: role of the hormonal secretion pattern'

Inflammation-based scores in a large cohort of adrenocortical carcinoma and adrenocortical adenoma: role of the hormonal secretion pattern

Fetched: July 5th, 2024, 2:00am UTC by A Mangone

J Endocrinol Invest. 2024 Jul 4. doi: 10.1007/s40618-024-02426-y. Online ahead of print.

ABSTRACT

BACKGROUND: Serum inflammation-based scores can predict clinical outcome in several cancer types, including adrenocortical carcinoma (ACC). It is unclear whether the extent of inflammation-based scores alterations in ACC reflects malignancy, steroid excess, or both.

METHODS: We investigated a large retrospective cohort of adrenocortical adenomas (ACA, n = 429) and ACC (n = 61) with available baseline full blood count and hormonal evaluation. We examined the relationship between different inflammation-based scores [neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), and prognostic nutrition index (PNI)] and both malignancy and steroid secretion patterns.

RESULTS: All inflammation-based scores differed between ACC and ACA: patients with ACC had higher NLR, PLR, SII and lower LMR and PNI levels compared to ACA (all p values < 0.001). NLR showed a positive correlation with cortisol levels after overnight 1 mg-dexamethasone suppression test (1 mg-DST), both in ACC and ACA (p < 0.01). The ROC curve analysis determined NLR > 2.6 as the best cut-off to discriminate ACC from ACA [AUC = 0.846, p < 0.01]. At multivariable analysis, NLR > 2.6 was independently associated with ACC, 1 mg-DST cortisol levels and age, but not with tumour size. Considering the ACC, NLR and SII were higher and PNI was lower in patients with cortisol excess compared to those without cortisol excess (p = 0.002, p = 0.007, and p = 0.044 respectively). Finally, LMR and NLR differed between inactive-ACC (n = 10) and inactive-ACA (n = 215) (p = 0.040 and p = 0.031, respectively).

CONCLUSION: Inflammation-based scores are related to steroid secretion both in ACC and ACA. ACCs present a higher grade of inflammation regardless of their hormonal secretion, likely as a feature of malignancy itself.

PMID:38965182 | DOI:10.1007/s40618-024-02426-y

Permalink for 'Vascular endothelial growth factor and endocan expression in adrenal cortical tumors and their relationship with histopathological prognostic parameters'

Vascular endothelial growth factor and endocan expression in adrenal cortical tumors and their relationship with histopathological prognostic parameters

Fetched: July 1st, 2024, 2:00am UTC by Melia KarakÃ¶se

Endocr J. 2024 Aug 8;71(8):789-797. doi: 10.1507/endocrj.EJ24-0032. Epub 2024 Jun 29.

ABSTRACT

The aim of this study was to determine the tissue expressions of vascular endothelial growth factor (VEGF) and endocan in adrenal cortical tumors and the factors associated with them. The study included 6 subjects with adrenocortical adenoma (ACA), 7 subjects with adrenocortical carcinoma (ACC), and 13 control subjects with a normal adrenal cortex. The status of VEGF and endocan expression was determined by the proportions of cells staining on a scale ranging from negative (not staining at all) to strongly positive. VEGF expression was detected in 1 (16.7%) of 6 subjects in the ACA group and in 6 (85.7%) of 7 subjects in the ACC group. VEGF expression was not detected in any of the subjects in the control group. Endocan expression was detected in 6 (100%) of 6 subjects in the ACA group and in 7 (100%) of 7 subjects in the ACC group, while it was detected in only 4 (30.7%) of 13 subjects in the control group. VEGF was expressed with a high frequency in subjects with ACC and with a low frequency in subjects with ACA, but it was not expressed in subjects with normal adrenal cortex tissue. Although endocan was expressed with a higher frequency in subjects with ACC and ACA, it was also expressed in subjects with normal adrenal cortex tissue. The percentage of cells expressed endocan in subjects with ACC was also significantly higher than in subjects with both ACA and normal adrenal cortex.

PMID:38945931 | DOI:10.1507/endocrj.EJ24-0032

Comprehensive genomic analysis of adrenocortical carcinoma reveals genetic profiles associated with patient survival

Fetched: June 28th, 2024, 2:00am UTC by A Sun-Zhang

ESMO Open. 2024 Jul;9(7):103617. doi: 10.1016/j.esmoop.2024.103617. Epub 2024 Jun 26.

ABSTRACT

BACKGROUND: Adrenocortical carcinoma (ACC) is one of the most lethal endocrine malignancies and there is a lack of clinically useful markers for prognosis and patient stratification. Therefore our aim was to identify clinical and genetic markers that predict outcome in patients with ACC.

METHODS: Clinical and genetic data from a total of 162 patients with ACC were analyzed by combining an independent cohort consisting of tumors from Yale School of Medicine, Karolinska Institutet, and DÃ¼sseldorf University (YKD) with two public databases [The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO)]. We used a novel bioinformatical pipeline combining differential expression and messenger RNA (mRNA)- and DNA-dependent survival. Data included reanalysis of previously conducted whole-exome sequencing (WES) for the YKD cohort, WES and RNA data for the TCGA cohort, and RNA data for the GEO cohort.

RESULTS: We identified 3903 significant differentially expressed genes when comparing ACC and adrenocortical adenoma, and the mRNA expression levels of 461/3903 genes significantly impacted survival. Subsequent analysis revealed 45 of these genes to be mutated in patients with significantly worse survival. The relationship was significant even after adjusting for stage and age. Protein-protein interaction showed previously unexplored interactions among many of the 45 proteins, including the cancer-related proteins DNA polymerase delta 1 (POLD1), aurora kinase A (AURKA), and kinesin family member 23 (KIF23). Furthermore 14 of the proteins had significant interactions with TP53 which is the most frequently mutated gene in the germline of patients with ACC.

CONCLUSIONS: Using a multiparameter approach, we identified 45 genes that significantly influenced survival. Notably, many of these genes have protein interactions not previously implicated in ACC. These findings may lay the foundation for improved prognostication and future targeted therapies.

PMID:38935991 | PMC:PMC11260375 | DOI:10.1016/j.esmoop.2024.103617

Current Management Strategies and Outcomes in Children With Adrenocortical Carcinomaz

Fetched: June 27th, 2024, 2:00am UTC by Ioannis A Ziogas

J Surg Res. 2024 Jun 25;301:110-117. doi: 10.1016/j.jss.2024.04.086. Online ahead of print.

ABSTRACT

INTRODUCTION: Adrenocortical carcinoma (ACC) is a rare but aggressive pediatric endocrine tumor. However, there is no recent US national report on the management or outcomes of pediatric ACC. We aimed to examine the clinical characteristics, current management strategies, and outcomes of pediatric ACC.

METHODS: In this retrospective National Cancer Database study between 2004 and 2019, children (<18 y) with ACC were included. Overall survival was examined by means of Kaplan-Meier method, log-rank tests, and Cox regression modeling.

RESULTS: Seventy-eight children with ACC were included. The median age was 10 y, the median tumor size was 10.2 cm, and 35.9% had metastasis at diagnosis. Most patients underwent surgical treatment (84.6%), 56.4% received chemotherapy, and 7.7% received radiation. The 1-, 3-, and 5-y overall survival rates were 87.0%, 62.0%, and 60.1%, respectively. In unadjusted analysis, surgical treatment was associated with improved overall survival (log-rank test, P < 0.001). In multivariable Cox regression, metastasis at diagnosis was associated with inferior overall survival (hazard ratio: 2.72, 95% confidence interval: 1.15-6.40, P = 0.02), when adjusting for age, tumor size, receipt of surgical treatment, and chemotherapy. In patients with nonmetastatic ACC, increasing age was associated with inferior overall survival (hazard ratio: 1.12, 95% confidence interval: 1.00-1.24, P = 0.04), when adjusting for tumor size, receipt of surgical treatment, and chemotherapy.

CONCLUSIONS: Most children with ACC in the USA undergo surgical treatment with about half of these also receiving chemotherapy. Metastasis at diagnosis was independently associated with inferior overall survival; in patients with nonmetastatic ACC, increasing age was independently associated with inferior overall survival.

PMID:38925097 | DOI:10.1016/j.jss.2024.04.086

Permalink for 'Assessment of prognostic factors in pediatric adrenocortical tumors: The modified pediatric S-GRAS score in an international multicenter cohort: A work from the ENSAT-PACT working group'

Assessment of prognostic factors in pediatric adrenocortical tumors: The modified pediatric S-GRAS score in an international multicenter cohort: A work from the ENSAT-PACT working group

Fetched: June 27th, 2024, 2:00am UTC by Riedmeier Maria

Eur J Endocrinol. 2024 Jul 2;191(1):64-74. doi: 10.1093/ejendo/lvae079.

ABSTRACT

OBJECTIVE: Pediatric adrenocortical carcinoma (pACC) is rare, and prognostic stratification remains challenging. We aimed to confirm the prognostic value of the previously published pediatric scoring system (pS-GRAS) in an international multicenter cohort.

DESIGN: Analysis of pS-GRAS items of pACC from 6 countries in collaboration of ENSAT-PACT, GPOH-MET, and IC-PACT.

METHODS: We received patient data of the pS-GRAS items including survival information from 9 centers. PS-GRAS score was calculated as a sum of tumor stage (1 = 0; 2-3 = 1; 4 = 2 points), grade (Ki67 index: 0%-9% = 0; 10%-19% = 1; â‰¥20% = 2 points), resection status (R0 = 0; RX/R1/R2 = 1 point), age (<4 years = 0; â‰¥4 years = 1 point), and hormone production (androgen production = 0; glucocorticoid-/mixed-/no-hormone production = 1 point) generating 8 scores and 4 groups (1: 0-2, 2: 3-4, 3: 5, 4: 6-7). Primary endpoint was overall survival (OS).

RESULTS: We included 268 patients with median age of 4 years. The analysis of the pS-GRAS score showed a significantly favorable prognosis in patients with a lower scoring compared to higher scoring groups (5-year OS: Group 1 98%; group 2 87% [hazard ratio {HR} of death 3.6, 95% CI of HR 1.6-8.2]; group 3 43% [HR of death 2.8, 95% CI 1.9-4.4]; group 4: OS 18% [HR of death 2.1, 95% CI 1.7-2.7]). In the multivariable analysis, age (HR of death 3.5, 95% CI 1.8-7.0), resection status (HR of death 5.5, 95% CI 2.7-11.1), tumor stage (HR of death 1.9, 95% CI of HR 1.2-3.0), and Ki67 index (HR of death 1.7, 95% CI 1.2-2.4) remained strong independent outcome predictors. Especially infants < 4 years showed more often low-risk constellations with a better OS for all tumor stages.

CONCLUSION: In an international multicenter study, we confirmed that the pS-GRAS score is strongly associated with overall survival among patients with pACC. Age, resection status, stage, and Ki67 index are important parameters for risk stratification.

PMID:38924056 | DOI:10.1093/ejendo/lvae079

Targeted NGS Molecular Profiling and Its Clinical Application in Adrenocortical Cancer

Fetched: June 26th, 2024, 2:00am UTC by Francesca Cioppi

Eur J Endocrinol. 2024 Jul 2;191(1):17-30. doi: 10.1093/ejendo/lvae077.

ABSTRACT

OBJECTIVE: Adrenal cortical carcinoma (ACC) is a rare malignancy with a generally poor but heterogeneous prognosis, especially depending on the tumour stage at diagnosis. Identification of somatic gene alterations combined with clinical/histopathological evaluation of the tumour can help improve prognostication. We applied a simplified targeted-Next-Generation Sequencing (NGS) panel to characterise the mutational profiles of ACCs, providing potentially relevant information for better patient management.

DESIGN AND METHODS: Thirty frozen tumour specimens from a local ACC series were retrospectively analysed by a custom-NGS panel (CDKN2A, CTNNB1, DAXX, MED12, NF1, PRKAR1A, RB1, TERT, TP53, ZNRF3) to detect somatic prioritised single-nucleotide variants. This cohort was integrated with 86 patients from the ACC-TCGA series bearing point-mutations in the same genes and their combinations identified by our panel. Primary endpoints of the analysis on the total cohort (113 patients) were overall survival (OS) and progression-free survival (PFS), and hazard ratio (HR) for the different alterations grouped by the signalling pathways/combinations affected.

RESULTS: Different PFS, OS, and HR were associated to the different pathways/combinations, being NF1 + TP53 and Wnt/Î²-catenin + Rb/p53 combined mutations the most deleterious, with a statistical significance for progression HR which is retained only in low-(I/II) stages-NF1 + TP53 combination: HR = 2.96[1.01-8.69] and HR = 13.23[3.15-55.61], all and low stages, respectively; Wnt/Î²-catenin + Rb/p53 combined pathways: HR = 6.47[2.54-16.49] and HR = 16.24[3.87-68.00], all and low-stages, respectively.

CONCLUSIONS: A simplified targeted-NGS approach seems the best routinely applicable first step towards somatic genetic characterisation of ACC for prognostic assessment. This approach proved to be particularly promising in low-stage cases, suggesting the need for more stringent surveillance and personalised treatment.

PMID:38917236 | DOI:10.1093/ejendo/lvae077

Permalink for 'Predictive value of C-X-C motif chemokine receptor 4-directed molecular imaging in patients with advanced adrenocortical carcinoma'

Predictive value of C-X-C motif chemokine receptor 4-directed molecular imaging in patients with advanced adrenocortical carcinoma

Fetched: June 20th, 2024, 2:00am UTC by Wiebke Schloetelburg

Eur J Nucl Med Mol Imaging. 2024 Jun 19. doi: 10.1007/s00259-024-06800-z. Online ahead of print.

ABSTRACT

BACKGROUND: In patients affected with adrenocortical carcinoma (ACC), C-X-C motif chemokine receptor 4 (CXCR4) is highly expressed in sites of disease in an ex-vivo setting. We aimed to determine the predictive value of CXCR4-targeting [⁶⁸Ga]Ga-PentixaFor PET/CT for outcome when compared to clinical parameters.

METHODS: We identified 41 metastasized ACC patients imaged with [⁶⁸Ga]Ga-PentixaFor PET/CT. Scans were assessed visually and on a quantitative level by manually segmenting the tumor burden (providing tumor volume [TV], peak/mean/maximum standardized uptake values [SUV] and tumor chemokine receptor binding on the cell surface [TRB], defined as SUVmean multiplied by tumor volume). Clinical parameters included sex, previous therapies, age, Weiss-Score, and Ki67 index. Following imaging, overall survival (OS) was recorded.

RESULTS: After [⁶⁸Ga]Ga-PentixaFor PET/CT, median OS was 9 months (range, 1-96 months). On univariable analysis, only higher TRB (per 10 ml, HR 1.004, 95%CI: 1.0001-1.007, P = 0.005) and presence of CXCR4-positive peritoneal metastases (PM) were associated with shorter OS (HR 2.03, 95%CI: 1.03-4.02, P = 0.04). Presence of CXCR4-positive liver metastases (LM) trended towards significance (HR 1.85, 0.9-4.1, P = 0.11), while all other parameters failed to predict survival. On multivariable analysis, only TRB was an independent predictor for OS (HR 1.0, 95%CI: 1.00-1.001, P = 0.02). On Kaplan-Meier analysis, TRB above median (13.3 months vs. below median, 6.4 months) and presence of CXCR4-positive PM (6.4 months, vs. no PM, 11.4 months) were associated with shorter survival (P < 0.05, respectively). Presence of LM, however, was also linked to less favorable outcome (8.5 months vs. no LM, 18.1 months), without reaching significance (P = 0.07).

CONCLUSIONS: In advanced ACC, elevated tumor chemokine receptor binding on the tumor cell surface detected through [⁶⁸Ga]Ga-PentixaFor PET/CT is an independent predictor for OS, while other imaging and clinical parameters failed to provide relevant prognostic information.

PMID:38896128 | DOI:10.1007/s00259-024-06800-z

RPN1: a pan-cancer biomarker and disulfidptosis regulator

Fetched: June 18th, 2024, 2:00am UTC by Xing Wang

Transl Cancer Res. 2024 May 31;13(5):2518-2534. doi: 10.21037/tcr-24-581. Epub 2024 May 29.

ABSTRACT

BACKGROUND: Elevated expression of SLC7A11, in conjunction with glucose deprivation, has revealed disulfidptosis as an emerging cell death modality. However, the prevalence of disulfidptosis across tumor cell lines, irrespective of SLC7A11 levels, remains uncertain. Additionally, deletion of the ribophorin I (RPN1) gene imparts resistance to disulfidptosis, yet the precise mechanism linking RPN1 to disulfidptosis remains elusive. The aim of this study is to determine the mechanism of RPN1-induced disulfidptosis and to determine the possibility of RPN1 as a pan-cancer marker.

METHODS: We hypothesized the widespread occurrence of disulfidptosis in various tumor cells, and proposed that RPN1-mediated disulfidptosis may be executed through cell skeleton breakdown. Experimental validation was conducted via flow cytometry, immunofluorescence, and western blot techniques. Furthermore, given RPN1's status as an emerging cell death marker, we utilized bioinformatics to analyze its expression in tumor tissues, clinical relevance, mechanisms within the tumor microenvironment, and potential for immunotherapy.

RESULTS: Conducting experiments on breast cancer (MDA-MB-231) and lung cancer (A549) cell lines under glucose-starved conditions, we found that RPN1 primarily induces cell skeleton breakdown to facilitate disulfidptosis. RPN1 demonstrated robust messenger RNA (mRNA) expression across 16 solid tumors, validated by data from 12 tumor types in the Gene Expression Omnibus (GEO). Across 12 cancer types, RPN1 exhibited significant diagnostic potential, particularly excelling in accuracy for glioblastoma (GBM). Elevated RPN1 expression in tumor tissues was found to correlate with improved overall survival (OS) in certain cancers [diffuse large B-cell lymphoma (DLBC) and thymoma (THYM)] but poorer prognosis in others [adrenocortical carcinoma (ACC), kidney chromophobe (KICH), brain lower grade glioma (LGG), liver hepatocellular carcinoma (LIHC), and pancreatic adenocarcinoma (PAAD)]. RPN1 is enriched in immune-related pathways and correlates with immune scores in tumor tissues. In urothelial carcinoma (UCC), RPN1 demonstrates potential in predicting the efficacy of anti-programmed cell death ligand 1 (PD-L1) immune therapy.

CONCLUSIONS: This study underscores RPN1's role in facilitating disulfidptosis, its broad relevance as a pan-cancer biomarker, and its association with the efficacy of anti-PD-L1 immune therapy.

PMID:38881923 | PMC:PMC11170529 | DOI:10.21037/tcr-24-581

Permalink for 'The algorithm for morphological assessment of malignant potential of adrenocortical tumors using mathematical modeling method'

The algorithm for morphological assessment of malignant potential of adrenocortical tumors using mathematical modeling method

Fetched: June 18th, 2024, 2:00am UTC by L S Urusova

Arkh Patol. 2024;86(3):21-29. doi: 10.17116/patol20248603121.

ABSTRACT

OBJECTIVE: To develop the mathematical model with high sensitivity and specificity to assess the malignant potential of adrenal cortical tumors, which can be used to diagnose adrenocortical carcinoma (ACC) in adults.

MATERIAL AND METHODS: Pathomorphological examination of surgical and consultative material of adrenocortical neoplasms was carried out. All cases were verified according to the WHO Classification of adrenal gland tumors (5^th ed., 2022), the tumor's histogenesis was confirmed by immunohistochemical examination. Statistical analysis of the histological and immunohistochemical factors in terms of their value in relation to the diagnosis of ACC was carried out on Python 3.1 in the Google Colab environment. ROC analysis was used to identify critical values of predictors. The cut-off point was selected according to the Youden`s index. Logistic regression analysis using l1-regularisation was performed. To validate the model, the initial sample was divided into training and test groups in the ratio of 9:1, respectively.

RESULTS: The study included 143 patients divided into training (128 patients) and test (15 patients) samples. A prognostic algorithm was developed, which represent a diagnostically significant set of indicators of the currently used Weiss scale. The diagnosis is carried out in 3 stages. This mathematical model showed 100% accuracy (95% CI: 96-100%) on the training and test samples.

CONCLUSION: The developed algorithm could solve the problem of subjectivity and complexity in the interpretation of some of the criteria of current diagnostic algorithms. The new model is unique in that, unlike others, it allows verification of all morphological variants of ACC.

PMID:38881002 | DOI:10.17116/patol20248603121

Permalink for 'Clinical outcomes of image-guided therapies in patients with adrenocortical carcinoma: a tertiary referral center retrospective study'

Clinical outcomes of image-guided therapies in patients with adrenocortical carcinoma: a tertiary referral center retrospective study

Fetched: June 14th, 2024, 2:00am UTC by Brenda Chahla

Oncologist. 2024 Jun 13:oyae130. doi: 10.1093/oncolo/oyae130. Online ahead of print.

ABSTRACT

BACKGROUND: Image-guided therapies (IGTs) are commonly used in oncology, but their role in adrenocortical carcinoma (ACC) is not well defined.

MATERIALS AND METHODS: A retrospective review of patients with ACC treated with IGTs. We assessed response to therapy using RECIST v1.1, time to next line of systemic therapy, disease control rate (DCR), local tumor progression-free survival (LTPFS), and complications of IGTs (based on the Common Terminology Criteria for Adverse Events [CTCAE] version 5.0).

RESULTS: Our cohort included 26 patients (median age 56 years [range 38-76]; n = 18 female) who had 51 IGT sessions to treat 86 lesions. IGTs modalities included cryoablation (n = 49), microwave ablation (n = 21), combined microwave and bland trans-arterial embolization (n = 8), bland trans-arterial embolization alone (n = 3), radio-embolization (n = 3), and radiofrequency ablation (n = 2). DCR was 81.4% (70 out of 86), of which 66.3% of tumors showed complete response, 18.6% showed progressive disease, 8.1% showed partial response, and 7.0% showed stable disease. LTPFS rates were 73% and 63% at 1 and 2 years, respectively. Fourteen lesions underwent re-ablation for incomplete response on initial treatment. Sixteen patients (61.5%) received new systemic therapy following IGTs, with a median time to systemic therapy of 12.5 months (95% CI: 8.6 months upper limit not reached). There was 1 reported CTCAE grade 3 adverse event (biloma) following IGT.

CONCLUSIONS: IGT use in properly selected patients with ACC is safe and associated with prolonged disease control and delay in the need for systemic therapy.

PMID:38869364 | DOI:10.1093/oncolo/oyae130

Adrenal tumors: current standards in clinical management

Fetched: June 13th, 2024, 2:00am UTC by Carmina Teresa FuÃŸ

Inn Med (Heidelb). 2024 Jul;65(7):632-641. doi: 10.1007/s00108-024-01727-x. Epub 2024 Jun 12.

ABSTRACT

Adrenal tumors are among the most common tumors in humans. They are most frequently discovered incidentally during abdominal imaging for other reasons or due to clinical symptoms (e.g. Conn's or Cushing's syndrome, pheochromocytoma or androgen excess). Although over 80% of adrenal tumors are benign, in cases of hormone excess, they are associated with significantly increased morbidity. In highly malignant adrenocortical carcinoma (ACC), early diagnosis is of particular prognostic relevance. Therefore, this review presents the diagnostic procedure for what are referred to as adrenal incidentalomas and provide recommendations for the management of ACC and pheochromocytomas/paragangliomas (PPGL). In primary diagnosis, sufficient hormone diagnostics is required for all adrenal tumors, as this is the only way to identify all patients with relevant hormone excess. Imaging has increasingly improved in recent years and allows a reliable assessment of the tumor's malignancy in most cases. Imaging of first choice is unenhanced computed tomography (CT), while magnetic resonance imaging (MRI) and fluorodeoxyglucose-18 positron emission tomography (FDG-PET/CT) are reserved for special situations, as published evidence on these procedures is more limited. The treatment of ACC and PPGL is complex and is carried out on an interdisciplinary basis at specialized centers. In the case of localized disease, surgery is the only curative treatment option. There are now clear recommendations for individualized adjuvant therapy for ACC. In metastatic disease, mitotane with or without platinum-containing chemotherapy is the standard. Other lines of therapy should be discussed with a reference center. Over 35% of PPGL have a germline mutation; therefore, genetic testing should be offered. In metastatic PPGL, an individual decision is required between active surveillance, radionuclide therapy, sunitinib or chemotherapy.

PMID:38864873 | DOI:10.1007/s00108-024-01727-x

Adrenocortical tumor manifesting as virilizing in a female child: Adenoma or carcinoma? A rare case report

Fetched: June 10th, 2024, 2:00am UTC by Fatima Breim

Int J Surg Case Rep. 2024 Jul;120:109878. doi: 10.1016/j.ijscr.2024.109878. Epub 2024 Jun 6.

ABSTRACT

INTRODUCTION: Adrenocortical tumors (ACTs) are rare endocrine neoplasms in children, with functional ACTs being more prevalent than non-functional types. Clinical manifestations typically include virilization, Cushing's syndrome, and hyperaldosteronism. Surgical intervention is the primary treatment for ACTs, with a significant risk of recurrence in adrenocortical carcinoma even after complete resection.

PRESENTATION OF CASE: This case presentation describes a 3.5-year-old female with generalized hirsutism and clitoral hypertrophy, leading to the discovery of a left adrenal tumor. The child underwent adrenalectomy, revealing a benign adrenal cortical adenoma. Unfortunately, due to loss of follow-up, the child later presented with pulmonary metastases and passed away, preventing further investigation into the source of metastases.

DISCUSSION: Adrenocortical tumors are uncommon in children, with the classification of ACTs into adenomas and carcinomas. To our knowledge, this is the third case of an adrenocortical tumor in a child in Syria. We highlight the challenges in managing pediatric ACTs and emphasize the importance of timely intervention and close monitoring to improve outcomes. Regular follow-up is crucial to detect complications early and optimize treatment strategies, especially considering the unpredictable behavior of these tumors.

CONCLUSION: This case confirms that distinguishing between adrenocortical adenoma and carcinoma can be challenging even histologically. Therefore, it is necessary to follow up after treating each case of adenoma in a child to prevent major complications.

PMID:38852562 | PMC:PMC11220538 | DOI:10.1016/j.ijscr.2024.109878

Multiple primary tumors in children: a clinicopathological analysis of four cases

Fetched: June 4th, 2024, 2:00am UTC by L X Li

Zhonghua Bing Li Xue Za Zhi. 2024 Jun 8;53(6):605-609. doi: 10.3760/cma.j.cn112151-20231024-00299.

ABSTRACT

Objective: To investigate the clinicopathological features of children with metachronous or synchronous primary tumors and to identify related genetic tumor syndromes. Methods: The clinicopathological data of 4 children with multiple primary tumors diagnosed in the Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China from 2011 to 2023 were collected. The histological, immunophenotypic and molecular characteristics were examined using H&E staining, immunohistochemical staining, PCR, Sanger sequencing and next-generation sequencing (NGS). The patients were followed up. Results: Case 1 was an 8-year-old boy with the adrenal cortical carcinoma, and 5 years later a poorly differentiated gastric adenocarcinoma was detected. Case 2 was a 2-year-old boy, presented with a left ventricular choroid plexus carcinoma, and a hepatoblastoma was detected 8 months later. Case 3 was a 9-month-old girl, diagnosed with renal rhabdoid tumor first and intracranial atypical teratoid/rhabdoid tumor (AT/RT) 3 months later. Case 4 was a 7-year-old boy and had a sigmoid colon adenocarcinoma 3 years after the diagnosis of a glioblastoma. The morphology and immunohistochemical features of the metachronous or synchronous primary tumors in the 4 cases were similar to the corresponding symptom-presenting/first-diagnosed tumors. No characteristic germ line mutations were detected in cases 1 and 2 by relevant molecular detection, and the rhabdoid tumor predisposition syndrome was confirmed in case 3 using NGS. Case 4 was clearly related to constitutional mismatch repair deficiency as shown by the molecular testing and clinical features. Conclusions: Childhood multiple primary tumors are a rare disease with histological morphology and immunophenotype similar to the symptom-presenting tumors. They are either sporadic or associated with a genetic (tumor) syndrome. The development of both tumors can occur simultaneously (synchronously) or at different times (metachronously). Early identification of the children associated with genetic tumor syndromes can facilitate routine tumor screening and early treatment.

PMID:38825907 | DOI:10.3760/cma.j.cn112151-20231024-00299

Comprehensive analysis to identify PUS7 as a prognostic biomarker from pan-cancer analysis to osteosarcoma validation

Fetched: June 1st, 2024, 2:00am UTC by Baokang Dong

Aging (Albany NY). 2024 May 30;16(10):9188-9203. doi: 10.18632/aging.205863. Epub 2024 May 30.

ABSTRACT

AIM: Pseudouridylation has demonstrated the potential to control the development of numerous malignancies. PUS7(Pseudouridine Synthase 7) is one of the pseudouridine synthases, but the literature on this enzyme is limited to several cancer types. Currently, no investigation has been performed on the systematic pan-cancer analysis concerning PUS7 role in cancer diagnosis and prognosis.

METHODS: Employing public databases, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), Human Protein Atlas (HPA), UALCAN and Tumor Immune Single-cell Hub (TISCH), this work investigated the PUS7 carcinogenesis in pan-cancer. Differential expression analysis, prognostic survival analysis and biological function were systematically performed. Furthermore, PUS7 potential as an osteosarcoma biomarker for diagnosis and prognosis was assessed in this study.

RESULTS: The findings indicated that PUS7 was overexpressed in the majority of malignancies. High PUS7 expression contributed to the poor prognosis among 11 cancer types, including Adrenocortical Cancer (ACC), Bladder Cancer (BLCA), Liver Cancer (LIHC), Kidney Papillary Cell Carcinoma (KIRP), Mesothelioma (MESO), Lower Grade Glioma (LGG), Kidney Chromophobe (KICH), Sarcoma (SARC), osteosarcoma (OS), Pancreatic Cancer (PAAD), and Thyroid Cancer (THCA). In addition, elevated PUS7 expression was linked to advanced TNM across multiple malignancies, including ACC, BLCA, KIRP, LIHC and PAAD. The function enrichment analysis revealed that PUS7 participates in E2F targets, G2M checkpoint, ribosome biogenesis, and rRNA metabolic process. Moreover, PUS7 is also a reliable biomarker and a potential therapeutic target for osteosarcoma.

CONCLUSIONS: In summary, PUS7 is a putative pan-cancer biomarker that reliably forecasts cancer patients' prognosis. In addition, this enzyme regulates the cell cycle, ribosome biogenesis, and rRNA metabolism. Most importantly, PUS7 possibly regulates osteosarcoma initiation and progression.

PMID:38819212 | PMC:PMC11164482 | DOI:10.18632/aging.205863

Features of an adrenal cortical carcinoma on CT scan: A case report

Fetched: May 31st, 2024, 2:00am UTC by Ramin Ebrahimi

Presse Med. 2024 Jun;53(2):104230. doi: 10.1016/j.lpm.2024.104230. Epub 2024 Mar 6.

NO ABSTRACT

PMID:38458314 | DOI:10.1016/j.lpm.2024.104230

Fully-automated CT derived body composition analysis reveals sarcopenia in functioning adrenocortical carcinomas

Fetched: May 29th, 2024, 2:01am UTC by Prasanna Santhanam

Sci Rep. 2024 May 28;14(1):12193. doi: 10.1038/s41598-024-62431-2.

ABSTRACT

Determination of body composition (the relative distribution of fat, muscle, and bone) has been used effectively to assess the risk of progression and overall clinical outcomes in different malignancies. Sarcopenia (loss of muscle mass) is especially associated with poor clinical outcomes in cancer. However, estimation of muscle mass through CT scan has been a cumbersome, manually intensive process requiring accurate contouring through dedicated personnel hours. Recently, fully automated technologies that can determine body composition in minutes have been developed and shown to be highly accurate in determining muscle, bone, and fat mass. We employed a fully automated technology, and analyzed images from a publicly available cancer imaging archive dataset (TCIA) and a tertiary academic center. The results show that adrenocortical carcinomas (ACC) have relatively sarcopenia compared to benign adrenal lesions. In addition, functional ACCs have accelerated sarcopenia compared to non-functional ACCs. Further longitudinal research might shed further light on the relationship between body component distribution and ACC prognosis, which will help us incorporate more nutritional strategies in cancer therapy.

PMID:38806535 | PMC:PMC11133428 | DOI:10.1038/s41598-024-62431-2

Permalink for 'Diagnostic and prognostic assessments of adrenocortical carcinomas by pathological features, immunohistochemical markers and reticular histochemistry staining'

Diagnostic and prognostic assessments of adrenocortical carcinomas by pathological features, immunohistochemical markers and reticular histochemistry staining

Fetched: May 28th, 2024, 2:00am UTC by Wenting Gan

Diagn Pathol. 2024 May 27;19(1):71. doi: 10.1186/s13000-024-01496-z.

ABSTRACT

BACKGROUND: Current diagnostic criteria of adrenocortical neoplasms are mostly based on morphology. The utility of immunohistochemistry (IHC) and histochemistry is limited.

MATERIALS AND METHODS: To evaluate the diagnostic and prognostic utility of clinicopathological features, morphology, ancillary biomarkers, and reticular histochemistry in adrenocortical neoplasms. We examined 28 adrenocortical carcinomas (ACCs) and 50 adrenocortical adenomas (ACAs) obtained from pathology archives. Clinical data were retrieved from medical records. Two pathologists independently assessed hematoxylin and eosin-stained slides, employing modified Weiss criteria for all tumors and Lin-Weiss-Bisceglia criteria for oncocytic variants. Immunohistochemical markers (Calretinin, alpha-inhibin, MelanA, SF-1, Ki-67, PHH3, IGF-2, Î²-catenin, P53, CYP11B1, CYP11B2, MLH1, MSH2, MSH6, PMS2, EPCAM) and Gomori's Silver histochemistry were applied. Statistical analysis utilized SPSS Statistics 26.

RESULTS: ACCs exhibited larger tumor sizes (P<0.001) and symptomatic presentations (P = 0.031) compared to ACAs. Parameters of modified Weiss criteria and angioinvasion demonstrated diagnostic value for ACCs. Six immunohistochemical antibodies((MelanA, Ki-67, IGF-2, Î²-catenin, P53 and CYP11B1) and reticulin framework alterations showed diagnostic value. Notably, Ki-67 and reticulin staining were most recommended. Evident reticulin staining was frequently present in ACCs (P<0.001). Ki-67 was significantly higher in ACCs (P<0.001). Twenty-one conventional and seven oncocytic entities showed different necrosis frequencies. Symptoms and Ki-67 index â‰¥ 30% were prognostic for ACCs, correlating with shorter survival.

CONCLUSIONS: This study emphasizes the diagnostic value of reticulin framework alterations and a high Ki-67 index. Markers such as CYP11B1, IGF2, P53, Î²-catenin and MelanA also contribute to the diagnosis of ACCs. Symptoms and Ki-67 index â‰¥ 30% predict shorter survival. These findings encourges the use of ancillary markers such as reticulin histochemistry and Ki-67 in the workup of evaluations of adrenocortical neoplasms.

PMID:38802933 | PMC:PMC11131238 | DOI:10.1186/s13000-024-01496-z

Adrenocortical cancer: late diagnosis of the disease on the example of a clinical case. Case report

Fetched: May 25th, 2024, 2:00am UTC by E A Starostina

Ter Arkh. 2023 Dec 28;95(12):1179-1184. doi: 10.26442/00403660.2023.12.202430.

ABSTRACT

Adrenocortical carcinoma (ACC) is a rare malignant tumor originating in the adrenal cortex and characterized by poor 5-year survival. It occurs with a frequency of 2-4 cases per 2 million in the population. Women are more frequently affected than men and it is mostly detected in the fourth and fifth decades. In the most of cases, the cancerogenesis occurs sporadically because of gene driver mutations in somatic adrenocortical cells, in other cases it can be found as part of a genetically determined syndrome such as Li-Fraumeni syndrome or Wermer's syndrome (multiple endocrine adenomatosis type I). ACC most frequently happens occurs without symptoms in the initial stages leading to poor diagnoses. Because of this lack of early detection, the tumor is not considered malignant reducing the benefits of further treatment. Sometimes the fact that the resected tumor is indeed adrenocortical carcinoma becomes clear only after recurrence, or after the appearance of metastases. We present a case of adrenocortical carcinoma in a 46-year-old woman who went to the doctor in 1.5 year after symptoms were manfested. This clinical case illustrates the consequences of late diagnosis of a malignant tumor. We would like to emphasize the importance of timely detection of a neoplasm, using all of the potential of laboratory-instrumental and genomic analysis. Due to low oncological awareness, our patient was slow to seek medical help, which in turn led not only to metastases, but also to complications in the cardiovascular system.

PMID:38785058 | DOI:10.26442/00403660.2023.12.202430

Permalink for 'Pharmacogenomic analysis in adrenocortical carcinoma reveals genetic features associated with mitotane sensitivity and potential therapeutics'

Pharmacogenomic analysis in adrenocortical carcinoma reveals genetic features associated with mitotane sensitivity and potential therapeutics

Fetched: May 24th, 2024, 2:00am UTC by Jie Zhang

Front Endocrinol (Lausanne). 2024 May 8;15:1365321. doi: 10.3389/fendo.2024.1365321. eCollection 2024.

ABSTRACT

BACKGROUND: Adrenocortical carcinoma (ACC) is an aggressive endocrine malignancy with limited therapeutic options. Treating advanced ACC with mitotane, the cornerstone therapy, remains challenging, thus underscoring the significance to predict mitotane response prior to treatment and seek other effective therapeutic strategies.

OBJECTIVE: We aimed to determine the efficacy of mitotane via an in vitro assay using patient-derived ACC cells (PDCs), identify molecular biomarkers associated with mitotane response and preliminarily explore potential agents for ACC.

METHODS: In vitro mitotane sensitivity testing was performed in 17 PDCs and high-throughput screening against 40 compounds was conducted in 8 PDCs. Genetic features were evaluated in 9 samples using exomic and transcriptomic sequencing.

RESULTS: PDCs exhibited variable sensitivity to mitotane treatment. The median cell viability inhibition rate was 48.4% (IQR: 39.3-59.3%) and -1.2% (IQR: -26.4-22.1%) in responders (n=8) and non-responders (n=9), respectively. Median IC50 and AUC were remarkably lower in responders (IC50: 53.4 ÂµM vs 74.7 ÂµM, P<0.0001; AUC: 158.0 vs 213.5, P<0.0001). Genomic analysis revealed CTNNB1 somatic alterations were only found in responders (3/5) while ZNRF3 alterations only in non-responders (3/4). Transcriptomic profiling found pathways associated with lipid metabolism were upregulated in responder tumors whilst CYP27A1 and ABCA1 expression were positively correlated to in vitro mitotane sensitivity. Furthermore, pharmacologic analysis identified that compounds including disulfiram, niclosamide and bortezomib exhibited efficacy against PDCs.

CONCLUSION: ACC PDCs could be useful for testing drug response, drug repurposing and guiding personalized therapies. Our results suggested response to mitotane might be associated with the dependency on lipid metabolism. CYP27A1 and ABCA1 expression could be predictive markers for mitotane response, and disulfiram, niclosamide and bortezomib could be potential therapeutics, both warranting further investigation.

PMID:38779454 | PMC:PMC11109426 | DOI:10.3389/fendo.2024.1365321

Venous thromboembolism in adrenocortical carcinoma: a retrospective analysis

Fetched: May 23rd, 2024, 2:00am UTC by Marta LaganÃ

Oncologist. 2024 Jul 5;29(7):575-580. doi: 10.1093/oncolo/oyae099.

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE) is a leading cause of death in patients with cancer. Limited data exist about VTE in patients with adrenocortical carcinoma (ACC). The primary objective of this study was to identify the prevalence of VTE in a cohort of patients with ACC. Secondary objectives were to determine the impact of VTE events on overall survival (OS) and to describe the characteristics of VTE in patients with ACC.

PATIENTS AND METHODS: We retrospectively reviewed data from 289 patients with ACC cared for at a major referral center from February 2010 to June 2022.

RESULTS: VTE prevalence was 18.7% (54 events). Thirty patients (55.6%) had pulmonary embolism (PE); 12 patients (22.2%) had deep vein thrombosis (DVT); and 12 patients (22.2%) had both PE and DVT. VTE occurred after ACC diagnosis in 50 patients (92.6%) including 44 patients (88%) with stage 3 or 4 ACC. VTEs were CTCAE grade â‰¤2 in 32 cases (59.3%), grade 3 in 17 (31.5%), and grade 4 in 2 (3.7%). Thirteen patients (24%) died within 6 months after VTE diagnosis, although there was no statistically significant association between VTE and overall survival.

CONCLUSION: Despite the potential to underestimate the prevalence of VTEs, we found a high frequency of VTE events in patients with ACC. A majority of VTEs occurred in the context of advanced ACC and we observed high short-term mortality. Further studies are needed to validate our findings and investigate mechanisms associated with VTE in ACC.

PMID:38776552 | PMC:PMC11224981 | DOI:10.1093/oncolo/oyae099

Li-Fraumeni Syndrome With Six Primary Tumors-Case Report

Fetched: May 21st, 2024, 2:00am UTC by Dejan StojiljkoviÄ‡

Case Rep Oncol Med. 2024 May 10;2024:6699698. doi: 10.1155/2024/6699698. eCollection 2024.

ABSTRACT

Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome associated with a high, lifetime risk of a broad spectrum of cancers caused by pathogenic germline TP53 mutations. Numerous different germline TP53 mutations have been associated with LFS, which has an exceptionally diverse clinical spectrum in terms of tumor type and age of onset. Our patient has developed six asynchronous tumors to date: a phyllode tumor of the breast, a pheochromocytoma, a rosette-forming glioneuronal tumor (RGNT), an adrenocortical carcinoma (ACC), a ductal carcinoma of the breast, and a thymoma. The occurrence of such a number of rare tumors is sporadic even among in the population of patients living with cancer predisposition syndromes. In this instance, the omission of pretest genetic counseling and thorough family tree analysis prior to selecting the test led to the oversight of an underlying TP53 likely pathogenic mutation (classified as Class 4). This emphasizes the necessity for such counseling to prevent overlooking crucial genetic information. Neglecting this step could have had profound implications on the patient's treatment, particularly considering the early onset and occurrence of multiple tumors, which typically raise suspicion of a hereditary component. The implications for family members must be considered.

PMID:38765733 | PMC:PMC11101246 | DOI:10.1155/2024/6699698

Cellular landscape of adrenocortical carcinoma at single-nuclei resolution

Fetched: May 19th, 2024, 2:00am UTC by David S Tourigny

Mol Cell Endocrinol. 2024 Sep 1;590:112272. doi: 10.1016/j.mce.2024.112272. Epub 2024 May 15.

ABSTRACT

Adrenocortical carcinoma (ACC) is a rare yet devastating tumour of the adrenal gland with a molecular pathology that remains incompletely understood. To gain novel insights into the cellular landscape of ACC, we generated single-nuclei RNA sequencing (snRNA-seq) data sets from twelve ACC tumour samples and analysed these alongside snRNA-seq data sets from normal adrenal glands (NAGs). We find the ACC tumour microenvironment to be relatively devoid of immune cells compared to NAG tissues, consistent with known high tumour purity values for ACC as an immunologically "cold" tumour. Our analysis identifies three separate groups of ACC samples that are characterised by different relative compositions of adrenocortical cell types. These include cell populations that are specifically enriched in the most clinically aggressive and hormonally active tumours, displaying hallmarks of reorganised cell mechanobiology and dysregulated steroidogenesis, respectively. We also identified and validated a population of mitotically active adrenocortical cells that strongly overexpress genes POLQ, DIAPH3 and EZH2 to support tumour expansion alongside an LGR4+ progenitor-like or cell-of-origin candidate for adrenocortical carcinogenesis. Trajectory inference suggests the fate adopted by malignant adrenocortical cells upon differentiation is associated with the copy number or allelic balance state of the imprinted DLK1/MEG3 genomic locus, which we verified by assessing bulk tumour DNA methylation status. In conclusion, our results therefore provide new insights into the clinical and cellular heterogeneity of ACC, revealing how genetic perturbations to healthy adrenocortical renewal and zonation provide a molecular basis for disease pathogenesis.

PMID:38759836 | DOI:10.1016/j.mce.2024.112272

Rare Cancers of Childhood Treatment (PDQÂ®): Patient Version

Fetched: May 16th, 2024, 2:00am UTC by PDQ Pediatric Treatment Editorial Board

2024 May 10. In: PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002â€“.

ABSTRACT

This PDQ cancer information summary has current information about the treatment of rare cancers of childhood. It is meant to inform and help patients, families, and caregivers. It does not give formal guidelines or recommendations for making decisions about health care.

Editorial Boards write the PDQ cancer information summaries and keep them up to date. These Boards are made up of experts in cancer treatment and other specialties related to cancer. The summaries are reviewed regularly and changes are made when there is new information. The date on each summary ("Date Last Modified") is the date of the most recent change. The information in this patient summary was taken from the health professional version, which is reviewed regularly and updated as needed, by the PDQ Pediatric Treatment Editorial Board.

PMID:26389276 | Bookshelf:NBK65835

Immune checkpoint molecules in adrenocortical carcinoma: hope for immunotherapy

Fetched: May 14th, 2024, 2:00am UTC by Enzo Lalli

J Clin Endocrinol Metab. 2024 May 13:dgae311. doi: 10.1210/clinem/dgae311. Online ahead of print.

NO ABSTRACT

PMID:38739542 | DOI:10.1210/clinem/dgae311

Exogenous steroid replacement in a pediatric patient with adrenocortical carcinoma receiving mitotane

Fetched: May 14th, 2024, 2:00am UTC by Catherine E Martin

Pediatr Blood Cancer. 2024 Aug;71(8):e31072. doi: 10.1002/pbc.31072. Epub 2024 May 12.

NO ABSTRACT

PMID:38736192 | DOI:10.1002/pbc.31072

Permalink for 'The effect of adjuvant mitotane therapy of the adrenocortical carcinoma on the endometrium and its clinical consequences in menstruating women. Literature review and authors' own experiences'

The effect of adjuvant mitotane therapy of the adrenocortical carcinoma on the endometrium and its clinical consequences in menstruating women. Literature review and authors' own experiences

Fetched: May 11th, 2024, 2:00am UTC by Piotr Szkodziak

Am J Cancer Res. 2024 Apr 15;14(4):1802-1814. doi: 10.62347/QKWF9884. eCollection 2024.

ABSTRACT

Adrenocortical carcinoma (ACC) is a malignant tumour that originates from the adrenal cortex. It is a highly aggressive cancer characterised by a poor prognosis with an annual incidence estimated to be up to 2 cases per million. In the adult population, ACC is diagnosed typically between 40 and 50 years of age, more often in women. Complete surgical resection of the tumour is the primary treatment method for ACC. Unfortunately, despite properly performed adrenalectomy, regional recurrences or distant metastases are detected in up to 90% of the patients. For that reason, adjuvant therapy is recommended. Mitotane is the most effective adrenal-specific agent used in adjuvant and palliative therapy. Two menstruating patients, after adrenalectomy due to ACC, during adjuvant mitotane therapy, have been included in the study. The study aimed to assess the effect of mitotane therapy on the endometrium and its clinical consequences, based on the analysis of these two cases and a review of the literature. It seems that menorrhagia may be expected during adjuvant mitotane therapy of ACC in menstruating women. Heavy uterine bleeding during menstruation may appear several months after the beginning of therapy. The likely mechanism for heavy menstrual bleeding is complex. Menorrhagia can occur due to the toxic effect of mitotane in the form of a haemorrhagic diathesis, while long-term treatment (over ten months) can lead to relative hypoestrogenism resulting in endometrial hyperplasia. Clinical signs of hypoestrogenism during mitotane treatment, have been described (including pre-puberty girls) and should be considered as a side-effect of the therapy. Menorrhagia may lead to severe anaemia, so this should be considered when planning mitotane treatment. Continuous gestagen therapy is helpful in the treatment of the above disorders. After over 60 years of experience with mitotane usage, knowledge about it is still insufficient, and further studies are required.

PMID:38726272 | PMC:PMC11076245 | DOI:10.62347/QKWF9884

Permalink for 'Survival nomogram and risk classification system for patients with adrenocortical carcinoma: a study based on the SEER database and external validation in China'

Survival nomogram and risk classification system for patients with adrenocortical carcinoma: a study based on the SEER database and external validation in China

Fetched: May 10th, 2024, 2:00am UTC by Zhizhou Li

Transl Androl Urol. 2024 Apr 30;13(4):493-508. doi: 10.21037/tau-23-571. Epub 2024 Apr 18.

ABSTRACT

BACKGROUND: Adrenocortical carcinoma (ACC) is an extremely rare and highly invasive malignant tumor. However, there is currently no reliable method to predict the prognosis of ACC. Our objective is to construct a nomogram and a risk classification system to predict the 1-year, 3-year, and 5-year overall survival (OS) of ACC.

METHODS: We retrieved clinicopathological data of patients diagnosed with ACC in The Surveillance, Epidemiology, and End Results (SEER) database and divided them into training and validation cohorts with a 7:3 ratio. Simultaneously, we collected an external validation cohort from The First Affiliated Hospital of Naval Medical University (Shanghai, China). Univariate and multivariate Cox analyses were performed to identify relevant risk factors, which were then combined to develop a correlation nomogram. The predictive performance of the nomogram was evaluated using the concordance index (C-index), receiver-operating characteristic curve (ROC), and calibration curves. Decision curve analysis (DCA) was applied to assess the clinical utility of the nomogram. In addition, Kaplan-Meier survival curves were generated to demonstrate the variation in OS between groups.

RESULTS: The final nomogram consisted of five factors: age, T, N, M, and history of chemotherapy. Our prognostic model demonstrated significant discriminative ability, with C-index and the area under the receiver operating characteristic (AUC) values exceeding 0.70. Additionally, DCA validated the clinical utility of the nomogram. In the entire cohort, the median OS for patients in the low- and high-risk groups was 70 and 10 months, respectively.

CONCLUSIONS: A nomogram and a corresponding risk classification system were developed in order to predict the OS of patients diagnosed with ACC. These tools have the potential to provide valuable support for patient counseling and assist in the decision-making process related to treatment options.

PMID:38721297 | PMC:PMC11074677 | DOI:10.21037/tau-23-571

Germline NGS targeted analysis in adult patients with sporadic adrenocortical carcinoma

Fetched: May 8th, 2024, 2:00am UTC by Maria Scatolini

Eur J Cancer. 2024 Jul;205:114088. doi: 10.1016/j.ejca.2024.114088. Epub 2024 Apr 26.

ABSTRACT

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare cancer that arises sporadically or due to hereditary syndromes. Data on germline variants (GVs) in sporadic ACC are limited. Our aim was to characterize GVs of genes potentially related to adrenal diseases in 150 adult patients with sporadic ACC.

METHODS: This was a retrospective analysis of stage I-IV ACC patients with sporadic ACC from two reference centers for ACC in Italy. Patients were included in the analysis if they had confirmed diagnosis of ACC, a frozen peripheral blood sample and complete clinical and follow-up data. Next generation sequencing technology was used to analyze the prevalence of GVs in a custom panel of 17 genes belonging to either cancer-predisposition genes or adrenocortical-differentiation genes categories.

RESULTS: We identified 18 GVs based on their frequency, enrichment and predicted functional characteristics. We found six pathogenic (P) or likely pathogenic (LP) variants in ARMC5, CTNNB1, MSH2, PDE11A and TP53 genes; and twelve variants lacking evidence of pathogenicity. New unique P/LP variants were identified in TP53 (p.G105D) and, for the first time, in ARMC5 (p.P731R). The presence of P/LP GVs was associated with reduced survival outcomes and had a significant and independent impact on both progression-free survival and overall survival.

CONCLUSIONS: GVs were present in 6.7 % of patients with sporadic ACC, and we identified novel variants of ARMC5 and TP53. These findings may improve understanding of ACC pathogenesis and enable genetic counseling of patients and their families.

PMID:38714106 | DOI:10.1016/j.ejca.2024.114088

Rare Cancer News & Clinical Trials » Adrenal Gland Cancer

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Adrenal Gland Cancer (566 unread)

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