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Adrenal Gland Cancer (544 unread)

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

Posted: November 21st, 2023, 3:00am GMT

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
Not yet recruiting

Metastasis-directed Therapy for Oligometastases of Breast Cancer

Posted: November 16th, 2023, 3:00am GMT

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, 3:00am GMT

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

Adebelizumab Combined With Chemotherapy and Radiotherapy Treat ES-SCLC

Posted: November 9th, 2023, 3:00am GMT

Conditions: Extensive Small Cell Lung Cancer
Interventions: Drug: Adebelizumab+Carboplatin+Etoposide+Concurrent Radiotherapy
Sponsors: Qianfoshan Hospital
Recruiting

11C-Metomidate PET/CT for Endocrine Hypertension and Characterisation of Adrenal Tumours

Posted: October 25th, 2023, 2:00am GMT

Conditions: Primary Aldosteronism Due to Aldosterone Producing Adenoma; Primary Aldosteronism; Adrenal Tumors
Interventions: Combination Product: 11C-Metomidate PET/CT imaging at Clinical Imaging Research Centre
Sponsors: Changi General Hospital; National University Health System, Singapore; Clinical Imaging Research Centre; Singapore General Hospital; Tan Tock Seng Hospital; Khoo Teck Puat Hospital; Ng Teng Fong General Hospital; Sengkang General Hospital
Recruiting

Skin Ion and Water Content in Human HYpertension (SKIWHY)

Posted: October 19th, 2023, 2:00am GMT

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

Clinical and Genetic Investigation of the Association Between Primary Aldosteronism and Thyroid Cancer

Posted: October 5th, 2023, 2:00am GMT

Conditions: Thyroid Cancer, Papillary; Primary Aldosteronism
Interventions: Diagnostic Test: Secreening test for primary aldosteronism and Confirmatory Testing
Sponsors: Instituto do Cancer do Estado de São Paulo; Fundação de Amparo à Pesquisa do Estado de São Paulo
Completed

Study of Radiotherapy and Pembrolizumab in People With Adrenocortical Carcinoma

Posted: October 4th, 2023, 2:00am GMT

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

National Registry of Rare Kidney Diseases

Posted: October 4th, 2023, 2:00am GMT

Conditions: Adenine Phosphoribosyltransferase Deficiency; AH Amyloidosis; AHL Amyloidosis; AL Amyloidosis; Alport Syndrome; Atypical Hemolytic Uremic Syndrome; Autoimmune Distal Renal Tubular Acidosis; Autosomal Recessive Proximal Renal Tubular Acidosis; Autosomal Recessive Distal Renal Tubular Acidosis; Autosomal Dominant Polycystic Kidney Disease; Autosomal Recessive Polycystic Kidney Disease; Bartter Syndrome; BK Nephropathy; C3 Glomerulopathy With Monoclonal Gammopathy; C3 Glomerulopathy; Calciphylaxis; Crystalglobulinaemia; Crystal-storing Histiocytosis; Cystinosis; Cystinuria; Dense Deposit Disease; Dent Disease; Denys-Drash Syndrome; Dominant Hypophosphataemia With Nephrolithiasis and/or Osteoporosis; Drug Induced Fanconi Syndrome; Drug-Induced Hypomagnesemia; Drug-Induced Nephrogenic Diabetes Insipidus; Epilepsy, Ataxia, Sensorineural Deafness and Tubulopathy; Fabry Disease; Familial Hypomagnesemia With Hypercalciuria and Nephrocalcinosis; Familial Primary Hypomagnesemia With Hypocalcuria; Familial Primary Hypomagnesaemia With Normocalciuria; Familial Renal Glucosuria; Fanconi Renotubular Syndrome 1; Fanconi Renotubular Syndrome 2; Fanconi Renotubular Syndrome 3; Fibrillary Glomerulonephritis; Fibromuscular Dysplasia; Focal Segmental Glomerulosclerosis; Generalised Pseudohypoaldosteronism Type 1; Gitelman Syndrome; Heavy-Metal-Induced Fanconi Syndrome; Hepatocyte Nuclear Factor 1-Beta-Associated Monogenic Diabetes; Hereditary Renal Hypouricemia; Hereditary Hypophosphatemic Rickets With Hypercalciuria; Hyperuricaemic Nephropathy; IgA Nephropathy; Immunotactoid Glomerulonephritis With Organised Microtubular Mononoclonal Immunoglobulin Deposits; Inherited Renal Cancer Syndromes; Intracapillary Monoclonal IgM Without Cryoglobulin; Intraglomerular/Capillary Lymphoma/Leukaemia; Isolated Autosomal Dominant Hypomagnesaemia Glaudemans Type; Liddle Syndrome; Light Chain Cast Nephropathy; Light Chain Proximal Tubulopathy Without Crystals; Light Chain Proximal Tubulopathy With Crystals; Lowe Syndrome; Membranous Nephropathy; Membranoproliferative Glomerulonephritis; Medullary Cystic Kidney Disease; Minimal Change Nephropathy; Mitochondrial Disease Of The Kidney; Monoclonal Immunoglobulin Deposition Disease; Nail Patella Syndrome; Nephrogenic Diabetes Insipidus; Nephrogenic Syndrome of Inappropriate Antidiuresis; Nephronophthisis; Primary Hypomagnesemia With Secondary Hypocalcemia; Primary Hyperoxaluria; Proliferative Glomerulonephritis With Monoclonal IgG Deposits; Proximal Tubulopathy Without Crystals; Pseudohypoaldosteronism Type 1, 2A-2E; Pure Red Cell Aplasia; Retroperitoneal Fibrosis; Sickle Cell Nephropathy; Shiga Toxin Associated Haemolytic Uraemic Syndrome; Steroid Resistant Nephrotic Syndrome; Steroid-Sensitive Nephrotic Syndrome; Thin Basement Membrane Nephropathy; Thrombotic Microangiopathy With Monoclonal Gammopathy; Type 1 Cryoglobulinaemic Glomerulonephritis; Tuberous Sclerosis; Unclassified Monoclonal Gammopathy Of Renal Significance; Vasculitis
Sponsors: UK Kidney Association
Recruiting

Intraoperative Hemodynamic Instability During Unilateral Adrenalectomy for Pheochromocytoma

Posted: October 2nd, 2023, 2:00am GMT

Conditions: Pheochromocytoma; Non-Secretory Adrenal Adenoma
Interventions: Procedure: adrenalectomy
Sponsors: Central Hospital, Nancy, France
Recruiting

Tranexamic Acid in Nasal Mohs Reconstruction

Posted: September 27th, 2023, 2:00am GMT

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
Not yet recruiting

Permalink for 'Comparison of Al18F-NOTA-LM3 With 68Ga-DOTATATE and 68Ga-NODAGA-LM3 PET/CT in Patients With Well-differentiated Neuroendocrine Tumors'

Comparison of Al18F-NOTA-LM3 With 68Ga-DOTATATE and 68Ga-NODAGA-LM3 PET/CT in Patients With Well-differentiated Neuroendocrine Tumors

Posted: September 27th, 2023, 2:00am GMT

Conditions: Neuroendocrine Tumors
Interventions: Diagnostic Test: Al18F-NOTA-LM3; Diagnostic Test: 68Ga-DOTATATE; Diagnostic Test: Al18F-NOTA-LM3; Diagnostic Test: 68Ga-NODAGA-LM3
Sponsors: Peking Union Medical College Hospital
Recruiting

Surgical Treatment of Adrenal Diseases- Laparoscopic vs. Robotic-assisted Adrenalectomy

Posted: September 22nd, 2023, 2:00pm GMT

Conditions: Adrenal Tumor; Adrenal Disease; Adrenal Mass; Adrenalectomy; Status; Adrenal Hyperplasia; Adrenal Gland Metastasis; Adrenal Cortex Diseases; Pheochromocytoma; Cushing Syndrome; Conn Adenoma; Adrenocortical Carcinoma; Adrenocortical Adenoma; Adrenocortical Tumor
Sponsors: University Hospital Olomouc; University Hospital Ostrava; Tomas Bata Hospital, Czech Republic; General University Hospital, Prague; University Hospital Hradec Kralove
Recruiting

Antibody Drug Conjugate ADCT-701 in Neuroendocrine Tumors and Carcinomas

Posted: September 18th, 2023, 2:00pm GMT

Conditions: Neuroendocrine Carcinomas; Neuroendocrine Tumors; Carcinoma, Neuroendocrine; Carcinoma, Adrenocortical; Carcinoma, Adrenal Cortical
Interventions: Drug: ADCT-701
Sponsors: National Cancer Institute (NCI)
Not yet recruiting

Permalink for 'The Effects of Sufentanil-remimazolam vs. Remifentanil-remimazolam Total Intravenous Anesthesia on Postoperative Pain in Laparoscopic-assisted Gastrectomy'

The Effects of Sufentanil-remimazolam vs. Remifentanil-remimazolam Total Intravenous Anesthesia on Postoperative Pain in Laparoscopic-assisted Gastrectomy

Posted: September 14th, 2023, 2:00am GMT

Conditions: Pheochromocytoma
Interventions: Drug: dexmedetomidine; Drug: 0.9% normal saline
Sponsors: Yonsei University
Completed

MT2022-01: MSCs for ALD

Posted: September 11th, 2023, 2:00am GMT

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

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

Posted: September 8th, 2023, 2:00am GMT

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

Permalink for 'Cold Dissection Versus Electrocautery Dissection in Endoscopic Nipple-Sparing Mastectomy and Immediate Implant-Based Reconstruction: A Randomized Controlled Trial'

Cold Dissection Versus Electrocautery Dissection in Endoscopic Nipple-Sparing Mastectomy and Immediate Implant-Based Reconstruction: A Randomized Controlled Trial

Posted: September 6th, 2023, 2:00pm GMT

Conditions: Breast Neoplasms
Interventions: Procedure: Cold dissection; Procedure: Electrocautery Dissection
Sponsors: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Recruiting

Improving Survivorship and Health-related Quality of Life in Patients With Primary Brain Tumours

Posted: August 28th, 2023, 2:00pm GMT

Conditions: Hypopituitarism; Radiotherapy-Induced Hypopituitarism; Brain Tumor
Intervention: Diagnostic Test: Dynamic testing of Pituitary Function
Sponsors: Royal College of Surgeons, Ireland; Beaumont Hospital
Not yet recruiting

Permalink for 'Cabozantinib in Combination With Atezolizumab for the Treatment of Patients With Locally Advanced, Metastatic, or Unresectable Adrenal Cortical Cancer'

Cabozantinib in Combination With Atezolizumab for the Treatment of Patients With Locally Advanced, Metastatic, or Unresectable Adrenal Cortical Cancer

Posted: August 23rd, 2023, 2:00pm GMT

Conditions: Locally Advanced Adrenal Cortex Carcinoma; Adrenal Cortical Carcinoma; Stage III Adrenal Cortex Carcinoma; Stage IV Adrenal Cortex Carcinoma AJCC v8; Unresectable Adrenal Cortex Carcinoma
Interventions: Biological: Atezolizumab; Procedure: Biospecimen Collection; Drug: Cabozantinib S-malate; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging
Sponsors: Emory University; National Cancer Institute (NCI)
Not yet recruiting

Effect of Acetaminophen Preemptive Analgesia on Postoperative Cognitive Function

Posted: August 22nd, 2023, 2:00pm GMT

Condition: Cognitive Function
Interventions: Drug: acetaminophen mannitol; Drug: Normal saline
Sponsor: Affiliated Hospital of Nantong University
Recruiting

Phase 1 Study of 68Ga-R8760

Posted: August 21st, 2023, 2:00am GMT

Conditions: Adrenocortical Carcinoma
Interventions: Drug: 68Ga-R8760 injection at pre-defined dose levels; Drug: 68Ga-R8760 injection
Sponsors: Radionetics Oncology
Recruiting

Evaluating Efficacy of Intravenous Carbetocin Versus Intramyometrial Injection of Adrenaline in Reducing Blood Loss

Posted: August 14th, 2023, 2:00am GMT

Conditions: Uterine Fibroid
Interventions: Drug: Carbetocin
Sponsors: Egymedicalpedia
Completed

$Permalink for 'Elotuzumab, CC-92480, and Dexamethasone for the Treatment of Relapsed or Refractory Myeloma After CD38- and BCMA-Targeted Therapies'$

Elotuzumab, CC-92480, and Dexamethasone for the Treatment of Relapsed or Refractory Myeloma After CD38- and BCMA-Targeted Therapies

Posted: August 8th, 2023, 2:00pm GMT

Conditions: Recurrent Multiple Myeloma; Refractory Multiple Myeloma
Interventions: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Drug: Dexamethasone; Procedure: Echocardiography; Biological: Elotuzumab; Procedure: Magnetic Resonance Imaging; Biological: Mezigdomide; Procedure: X-Ray Imaging
Sponsors: Abdullah Khan
Recruiting

Engaging Black Men in Colorectal Cancer Screening

Posted: August 7th, 2023, 2:00pm GMT

Conditions: Colorectal Cancer; CRC; Behavior
Intervention: Behavioral: mHealth Application
Sponsors: Virginia Commonwealth University; National Cancer Institute (NCI)
Recruiting

Cervical Epidural and Stellate Ganglion Block in Upper Limb Complex Regional Pain Syndrome

Posted: August 1st, 2023, 2:00am GMT

Conditions: Stellate Ganglion Block; Cervical Epidural; Complex Regional Pain Syndromes
Interventions: Drug: Ultrasound guided Stellate ganglion block; Drug: unilateral cervical epidural
Sponsors: Tanta University
Recruiting

Permalink for 'Liraglutide and Metformin Combination on Weight Loss, Metabolic - Endocrine Parameters and Pregnancy Rate in Women With PCOS, Obesity and Infertility'

Liraglutide and Metformin Combination on Weight Loss, Metabolic - Endocrine Parameters and Pregnancy Rate in Women With PCOS, Obesity and Infertility

Posted: July 19th, 2023, 2:00am GMT

Conditions: Polycystic Ovary Syndrome; Obesity; Infertility, Female
Interventions: Drug: Liraglutide + Metformin; Drug: Metformin
Sponsors: Mỹ Đức Hospital
Not yet recruiting

LRAMPS Versus LDP in Early-stage Left-sided Pancreatic Cancer Within Fudan Criteria

Posted: July 11th, 2023, 2:00pm GMT

Conditions: Left-sided Pancreatic Cancer
Interventions: Procedure: LRAMPS; Procedure: LDP
Sponsors: Fudan University; The Third Affiliated Hospital of Soochow University; Qilu Hospital of Shandong University
Recruiting

Minimally Invasive Esophagectomy Pain Control Trial

Posted: June 15th, 2023, 2:00pm GMT

Conditions: Postoperative Pain, Acute; Postoperative Complications
Interventions: Procedure: Thoracic epidural catheter; Procedure: Local intercostal nerve block; Procedure: Cryo-analgesia and intercostal nerve block; Procedure: Serratus plane catheter blocks and intercostal nerve blocks
Sponsor: Swedish Medical Center
Recruiting

Intercostal Cryoanalgesia for Acute Pain After VATS Lung Resection

Posted: June 9th, 2023, 2:00pm GMT

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'Université de Montréal (CHUM)
Recruiting

Intercostal Cryoanalgesia for Chronic Pain After VATS Lung Resection

Posted: June 1st, 2023, 2:00pm GMT

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'Université de Montréal (CHUM)
Recruiting

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

Posted: May 23rd, 2023, 2:00pm GMT

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

CXCR4 Targeted PET Imaging in APA Preoperative Localization Diagnosis

Posted: May 2nd, 2023, 2:00pm GMT

Condition: Aldosterone-Producing Adenoma
Intervention: Diagnostic Test: CXCR4
Sponsor: Zhongnan Hospital
Recruiting

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

Posted: April 28th, 2023, 2:00pm GMT

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

Ramadan Fasting in Secondary Adrenal Insufficiency Patients

Posted: April 25th, 2023, 2:00am GMT

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, 2:00pm GMT

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

Methods Decreasing Bleeding in Open Myomectomy

Posted: April 10th, 2023, 2:00pm GMT

Conditions: Misoprostol Allergy; Oxytocin Allergy; Tranexamic Acid Allergy; Ethamsylate Allergy; Myoma; Blood Loss, Surgical
Interventions: Drug: Misoprostol; Device: Tourniquet; Drug: Carbetocin; Drug: Oxytocin; Drug: combined TXA and ethamsylate; Drug: Vasopressin; Drug: Bupivacaine Hydrochloride 0.5 % Injectable Solution epinephrine
Sponsor: Cairo University
Recruiting

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

Posted: April 7th, 2023, 2:00am GMT

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

PADUA PREDICTION SCORE in Cirrhotic Patients

Posted: March 29th, 2023, 2:00pm GMT

Condition: Portal Thrombosis
Intervention:
Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Recruiting

Impact of Non-magnetic Screen Respiratory Self-guidance During MRI-guided Radiotherapy Sessions for Mobile Lesions

Posted: March 24th, 2023, 2:00pm GMT

Conditions: Patient With Radiotherapy (Linac MRI); Mobile Cancerous Lesion
Interventions: Combination Product: With non-magnetic screen
Sponsors: Centre Georges Francois Leclerc
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, 2:00pm GMT

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

Use of Virtual Reality for Surgical Planning in Neuroblastoma

Posted: March 23rd, 2023, 2:00pm GMT

Condition: Neuroblastoma
Interventions: Other: Immersive virtual reality imaging; Other: Gold standard imaging
Sponsor: Hospital Sant Joan de Deu
Recruiting

European Multicenter Study on Role of Lymph Node Dissection in Surgical Management of Adrenal Cortical Carcinoma

Posted: March 10th, 2023, 3:00pm GMT

Condition: Adrenocortical Carcinoma
Intervention: Procedure: Adrenalectomy with or without lymphadenectomy
Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Recruiting

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

Posted: March 6th, 2023, 3:00pm GMT

Conditions: Cancer; Adrenal
Interventions: Other: Blood sample; Other: Urine sample; Other: Tumor sample
Sponsors: Assistance Publique - Hôpitaux de Paris; National Cancer Institute, France
Not yet recruiting

Improving Cancer Screening and Follow-up in Community Health Centers

Posted: March 6th, 2023, 3:00pm GMT

Conditions: Breast Cancer Screening; Colorectal Cancer Screening; Implementation
Intervention: Other: Practice-Level Implementation Strategies
Sponsors: Harvard School of Public Health (HSPH); National Institutes of Health (NIH); National Cancer Institute (NCI)
Recruiting

Liver Transplantation With Two-stage Liver Resection in Unresectable Liver Cancer or Metastases (LTLR-LC)

Posted: March 1st, 2023, 3:00pm GMT

Conditions: Liver Transplant Disorder; Hepatic Cancer; End-stage Liver Disease
Intervention: Procedure: assisted liver transplantation combined with two-stage hepatectomy
Sponsors: RenJi Hospital; The Affiliated Hospital of Qingdao University; The First Affiliated Hospital of Zhengzhou University
Not yet recruiting

Effect of Sleep Disorder on the Development of Lung Tumors

Posted: February 27th, 2023, 3:00pm GMT

Condition: Sleep Disorder, Lung Tumor
Intervention:
Sponsor: RenJi Hospital
Not yet recruiting

Cohort Study of Adrenogenic Autonomic Cortisol Secretion

Posted: February 24th, 2023, 3:00pm GMT

Conditions: Diagnosis; Treatment; Adrenogenic Autonomic Cortisol Secretion
Intervention:
Sponsor: Chongqing Medical University
Not yet recruiting

The Efficacy and Safety of Chinese Domestic Surgical Robot System in Urological Telesurgery

Posted: February 22nd, 2023, 3:00pm GMT

Conditions: Renal Cell Carcinoma; Adrenal Tumor; Nonfunctioning Kidney; Renal Pelvis Carcinoma; Ureteral Tumor; Bladder Cancer; Prostate Cancer; Pelvic Tumor; Renal Cyst; Duplex Kidney; Renal Calculi; Ureteral Calculi; Ureteropelvic Junction Obstruction; Penile Cancer
Intervention: Device: telesurgery by domestic surgical robot
Sponsor: The Affiliated Hospital of Qingdao University
Recruiting

Tranexamic Acid During Upper GI Endoscopic Resection Procedures

Posted: January 18th, 2023, 3:00pm GMT

Conditions: Gastric Polyp; Gastric Neoplasm; Duodenal Neoplasms; Esophageal Neoplasms
Interventions: Drug: Tranexamic acid; Drug: Epinephrine injection
Sponsor: Assaf-Harofeh Medical Center
Recruiting

Baby Detect : Genomic Newborn Screening

Posted: January 18th, 2023, 3:00am GMT

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 Régional de la Citadelle; Centre Hospitalier Universitaire de Liege; University of Liege; Sanofi; Orchard Therapeutics; Takeda; Zentech-Lacar Company; Leon Fredericq Foundation
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, 3:00am GMT

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

A Study of Nivolumab, Ipilimumab, and Chemotherapy in Participants With Non-small Cell Lung Cancer

Posted: October 31st, 2022, 2:00am GMT

Conditions: Carcinoma, Non-Small-Cell Lung
Sponsors: Bristol-Myers Squibb
Recruiting

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

Posted: September 10th, 2022, 2:00am GMT

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

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

Posted: July 19th, 2022, 2:00am GMT

Conditions: Craniopharyngioma, Child; Craniopharyngioma; Recurrent Craniopharyngioma
Interventions: Drug: Nivolumab; Drug: DAY101
Sponsors: Sabine Mueller, MD, PhD; Bristol-Myers Squibb; Day One Biopharmaceuticals, Inc.
Recruiting

Metabolic Myopathy in Endocrinopathy

Posted: July 13th, 2022, 2:00am GMT

Conditions: Cushing Syndrome; Pheochromocytoma; Conns Syndrome; Metabolic Myopathy
Interventions: Procedure: Muscle biopsy
Sponsors: Barts & The London NHS Trust; Imperial College London; Queen Mary University of London
Terminated

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

Posted: July 7th, 2022, 2:00pm GMT

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
Recruiting

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

Posted: June 29th, 2022, 2:00pm GMT

Conditions: Autonomous Cortisol Secretion (ACS); ACTH-Independent Cushing Syndrome; ACTH-Independent Adrenal Cushing Syndrome, Somatic
Interventions: Drug: SPI-62 dose1; Drug: SPI-62 dose 2; Drug: SPI-62 dose 3; Drug: SPI-62 dose 4; Drug: Placebo
Sponsors: Sparrow Pharmaceuticals
Recruiting

A Study of Safety and Efficacy of Tildacerfont in Females With Polycystic Ovary Syndrome and Elevated Adrenal Androgens

Posted: May 11th, 2022, 2:00am GMT

Conditions: Polycystic Ovary Syndrome
Interventions: Drug: Tildacerfont; Drug: Placebo
Sponsors: Spruce Biosciences
Completed

Endoscopic Ultrasound-guided Radiofrequency Ablation in Primary Aldosteronism

Posted: May 10th, 2022, 2:00pm GMT

Conditions: Primary Aldosteronism; Aldosterone-Producing Adenoma
Interventions: Procedure: EUS-RFA of left adrenal gland; Procedure: adrenalectomy
Sponsors: Haukeland University Hospital
Recruiting

Tranexamic Acid During Colonic Endoscopic Resection Procedures

Posted: April 26th, 2022, 2:00pm GMT

Condition: Colon Neoplasm
Interventions: Drug: Tranexamic acid; Drug: Standard
Sponsor: Assaf-Harofeh Medical Center
Recruiting

Survivorship Plan HEalth REcord (SPHERE) Implementation Trial

Posted: April 26th, 2022, 2:00pm GMT

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

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

Posted: April 1st, 2022, 2:00am GMT

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
Recruiting

TAP vs QL for Postoperative Analgesia After DIEP Free Flap Breast Reconstruction

Posted: March 29th, 2022, 2:00am GMT

Conditions: Breast Cancer
Interventions: Procedure: TAP block; Procedure: QL Block
Sponsors: Ottawa Hospital Research Institute
Withdrawn

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

Posted: February 14th, 2022, 3:00pm GMT

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

Permalink for 'A Study Evaluating the Safety and Efficacy of ENV-101 (Taladegib) in Patients With Advanced Solid Tumors Harboring PTCH1 Loss of Function Mutations'

A Study Evaluating the Safety and Efficacy of ENV-101 (Taladegib) in Patients With Advanced Solid Tumors Harboring PTCH1 Loss of Function Mutations

Posted: January 20th, 2022, 3:00pm GMT

Condition: Solid Tumors With PTCH1 Loss-of-function Mutations
Intervention: Drug: ENV-101 (taladegib)
Sponsor: Endeavor Biomedicines, Inc.
Recruiting

Real-time Ultrasound Guidance for Thoracic Epidural Blocks

Posted: December 21st, 2021, 3:00pm GMT

Conditions: Analgesia; Thoracic Tumors; Abdomen Tumors; Rib Fractures
Intervention: Procedure: Real-time ultrasound guidance for thoracic epidural catheter placement.
Sponsor: University of Chile
Not yet recruiting

Permalink for 'Testing the Combination of Anti-Cancer Drugs Talazoparib and Temozolomide in Patients >= 18 Years Old With Advanced Stage Rare Cancers, RARE 2 Study'

Testing the Combination of Anti-Cancer Drugs Talazoparib and Temozolomide in Patients >= 18 Years Old With Advanced Stage Rare Cancers, RARE 2 Study

Posted: December 2nd, 2021, 3:00pm GMT

Conditions: Adrenal Gland Pheochromocytoma; Hematopoietic and Lymphoid System Neoplasm; Malignant Solid Neoplasm; Paraganglioma
Interventions: Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Talazoparib; Drug: Temozolomide
Sponsors: National Cancer Institute (NCI)
Recruiting

21DIF039: Prone to Supine Breast MRI II, P2S2 Breast MRI Trial

Posted: November 23rd, 2021, 3:00pm GMT

Condition: Breast Cancer Female
Intervention: Procedure: Supine MRI
Sponsors: Dartmouth-Hitchcock Medical Center; CairnSurgical, Inc.
Recruiting

Phase II Trial of Pembrolizumab Plus Lenvatinib in Advanced Adrenal Cortical Carcinoma

Posted: September 5th, 2021, 2:00am GMT

Conditions: Adrenocortical Carcinoma
Interventions: Drug: Pembrolizumab / Lenvatinib
Sponsors: National Cancer Center, Korea; MSD Korea Ltd.
Enrolling by invitation

Milademetan in Advanced/Metastatic Solid Tumors

Posted: August 19th, 2021, 2:00pm GMT

Conditions: Solid Tumors; Head and Neck Carcinoma; Cholangiocarcinoma; Sarcoma; Lung Adenocarcinoma; Bladder Urothelial Carcinoma; Stomach Adenocarcinoma; Breast Cancer Invasive; Ovarian Carcinoma; Cervical Cancer; Non Small Cell Lung Cancer; Gastric Cancer; Biliary Tract Cancer; Melanoma; Pancreas Cancer; MDM2 Gene Amplification; Testicular Germ Cell Tumor; Adrenocortical Carcinoma
Interventions: Drug: RAIN-32
Sponsors: Rain Oncology Inc
Terminated

Feasibility of 2 Interventions to Reduce Fatigue in Patients With Chemotherapy for Metastatic Colorectal Cancer

Posted: August 10th, 2021, 2:00pm GMT

Condition: Colorectal Cancer Metastatic
Interventions: Behavioral: Hypnosis; Behavioral: CBT
Sponsor: Institut du Cancer de Montpellier - Val d'Aurelle
Recruiting

Telehealth-Filter Ventilation ( COMET2P1 )

Posted: July 21st, 2021, 2:00pm GMT

Condition: Tobacco Use
Interventions: Other: Ventilated Cigarette Filter; Other: Unventilated Cigarette Filter
Sponsors: Masonic Cancer Center, University of Minnesota; Ohio State University
Recruiting

Tumescence in HNC Skin Graft Reconstruction

Posted: July 19th, 2021, 2:00pm GMT

Conditions: Head and Neck Cancer; Surgery--Complications; Graft Failure
Intervention: Procedure: Tumescence During STSG Harvest
Sponsor: University of California, Davis
Recruiting

Stereotactic MRI-guided Adaptive Radiation Therapy (SMART) in One Fraction

Posted: June 25th, 2021, 2:00pm GMT

Condition: Metastatic Carcinoma
Intervention: Radiation: Stereotactic ablative body radiation therapy
Sponsors: Baptist Health South Florida; Viewray Inc.
Recruiting

3D Laparoscopic Adrenalectomies for Adrenal Tumors

Posted: May 28th, 2021, 2:00am GMT

Conditions: Adrenal Tumor; Adrenalectomy; Status
Sponsors: Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta
Recruiting

B7-H3-Specific Chimeric Antigen Receptor Autologous T-Cell Therapy for Pediatric Patients With Solid Tumors (3CAR)

Posted: May 21st, 2021, 2:00pm GMT

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
Sponsor: St. Jude Children's Research Hospital
Recruiting

The Efficacy and Safety of Anlotinib in Patients With Metastatic Pheochromocytoma or Paraganglioma

Posted: April 27th, 2021, 2:00pm GMT

Conditions: Malignant Adrenal Gland Pheochromocytoma; Malignant Paraganglioma; Pheochromocytoma, Metastatic; Paraganglioma, Malignant; Paraganglioma, Extra-Adrenal
Intervention: Drug: anlotinib hydrochloride
Sponsor: Peking Union Medical College Hospital
Recruiting

Development of a Predictive Model for the Risk of Metastatic Disease in PPGLs, a Retrospective Cohort Study

Posted: March 9th, 2021, 3:00pm GMT

Conditions: Paraganglioma; Pheochromocytoma; Genetic Predisposition to Disease; Pathology; Somatic Mutation; Head and Neck Cancer; Neuroendocrine Tumors
Intervention:
Sponsor: Rigshospitalet, Denmark
Not yet 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, 3:00am GMT

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

Permalink for 'Iberdomide Alone or in Combination With Dexamethasone for the Treatment of Intermediate- or High-Risk Smoldering Multiple Myeloma'

Iberdomide Alone or in Combination With Dexamethasone for the Treatment of Intermediate- or High-Risk Smoldering Multiple Myeloma

Posted: March 1st, 2021, 3:00pm GMT

Condition: Smoldering Plasma Cell Myeloma
Interventions: Drug: Dexamethasone; Drug: Iberdomide Hydrochloride; Other: Quality-of-Life Assessment
Sponsors: Emory University; Bristol-Myers Squibb; National Cancer Institute (NCI)
Recruiting

Developing a Virtual Stress Management Intervention for Spousal/Partnered Caregivers of Solid Tumor Cancer Patients.

Posted: February 5th, 2021, 3:00pm GMT

Conditions: Breast Cancer; Lung Cancer; Colon Cancer; Solid Tumor, Adult
Interventions: Behavioral: PEPRR; Behavioral: Pep-Pal
Sponsors: University of Colorado, Denver; National Cancer Institute (NCI)
Recruiting

Safety & Efficacy of Durvalumab+Neoadjuvant Chemotherapy for High-risk Urothelial Carcinoma of the Upper Urinary Tract

Posted: November 5th, 2020, 3:00pm GMT

Conditions: Urothelial Carcinoma; Cancer
Intervention: Drug: Patients receiving neoadjuvant therapy before radical nephrectomy
Sponsors: Centre Hospitalier Universitaire de Nīmes; Pitié-Salpêtrière Hospital; Hôpital Bichat-Claude Bernard, 75018 Paris; Hopital Foch 92151 Suresnes; Institut Paoli-Calmettes; European Georges Pompidou Hospital; Saint-Louis Hospital, Paris, France; Centre Hospitalier Lyon Sud; Center Eugene Marquis; IUCT ONCOPOLE
Recruiting

Endoscopic Mucosal Resection Versus Endoscopic Submucosal Dissection for Colorectal Laterally Spreading Lesions.

Posted: October 20th, 2020, 2:00am GMT

Conditions: Neoplasms, Colorectal
Interventions: Procedure: Endoscopic mucosal resection (EMR); Procedure: Endoscopic submucosal dissection (ESD)
Sponsors: José Carlos Marín Gabriel; Spanish Society of Digestive Endoscopy
Recruiting

GROWing Up With Rare GENEtic Syndromes

Posted: July 9th, 2020, 2:00am GMT

Conditions: Prader-Willi Syndrome; PWS-like Syndrome; Silver Russel Syndrome; Congenital Hypopituitarism; Klinefelter (XXY-)Syndrome; Congenital Adrenal Hyperplasia; XXXXY Syndrome; XXYY Syndrome; XXXX Syndrome (Tetra-X Syndrome); Disorders of Sex Development; Turner Syndrome; 46, XY DSD; Tuberous Sclerosis; Neurofibromatosis; Albright Hereditaire Osteodystrofie; Cornelia de Lange Syndrome; Saethre-Chotzen Syndrome; 17p- Deletiesyndrome; VCF Syndrome; POLR3A Mutatie; Ohdo Syndrome; Jacobsen Syndrome / 11 q Syndrome; Myrhe Syndrome; CHARGE Syndrome; 1q25-32 Deletie; Bardet Biedl Syndrome; Rett Syndrome; 22q11 Deletion Syndrome; Allan-Herndon-Dudley Syndrome; Kallmann Syndrome; Rare Bone Disorders; Noonan Syndrome; Williams-Beuren Syndrome
Interventions: Diagnostic Test: Retrospective file studies
Sponsors: dr. Laura C. G. de Graaff-Herder
Recruiting

Testing Trametinib as a Potential Targeted Treatment in Cancers With GNAQ or GNA11 Genetic Changes (MATCH-Subprotocol S2)

Posted: June 19th, 2020, 2:00am GMT

Conditions: Advanced Lymphoma; Advanced Malignant Solid Neoplasm; Hematopoietic and Lymphoid Cell Neoplasm; Refractory Lymphoma; Refractory Malignant Solid Neoplasm; Refractory Multiple Myeloma
Interventions: Drug: Trametinib Dimethyl Sulfoxide
Sponsors: National Cancer Institute (NCI)
Active, not recruiting

Neuroendocrine and Adrenal Tumors

Posted: June 16th, 2020, 2:00pm GMT

Conditions: Neuroendocrine Tumors; Adrenal Tumor
Interventions: Other: No intervention
Sponsors: University of Pennsylvania
Not yet recruiting

SpotCheck: Comparison of Enhanced Telemedicine Versus In-person Evaluation for the Diagnosis of Skin Cancer

Posted: June 2nd, 2020, 2:00am GMT

Conditions: Skin Cancer
Interventions: Device: Nevisense 3.0; Device: Dermlite Cam; Procedure: Skin biopsy
Sponsors: NYU Langone Health
Active, not recruiting

Optimal Methods of Disease Progression and Survival Analysis in Children and Adults Patients With Adrenocortical Cancer (ACC)

Posted: April 22nd, 2020, 2:00am GMT

Conditions: Adrenocortical Carcinoma
Sponsors: National Cancer Institute (NCI)
Active, not recruiting

Permalink for 'Evaluation of the Clinical and Psychological Impact of Vitamin D Replacement in Adolescent Females at Risk for Polycystic Ovarian Syndrome (PCOS)'

Evaluation of the Clinical and Psychological Impact of Vitamin D Replacement in Adolescent Females at Risk for Polycystic Ovarian Syndrome (PCOS)

Posted: April 21st, 2020, 2:00am GMT

Conditions: Polycystic Ovarian Syndrome in Adolescent Females; Vitamin D Deficiency
Interventions: Drug: Vitamin D 4000IU daily; Drug: Placebo
Sponsors: Yale University
Not yet recruiting

Efficacy and Safety of Relacorilant in Patients With Cortisol-Secreting Adrenal Adenomas

Posted: March 16th, 2020, 2:00am GMT

Conditions: Hypercortisolism
Interventions: Drug: relacorilant; Other: Placebo
Sponsors: Corcept Therapeutics
Recruiting

Virtual Human Delivered Nutrition Module for Colorectal Cancer Prevention

Posted: December 10th, 2019, 3:00pm GMT

Condition: Colorectal Cancer
Interventions: Other: virtual technology - high interactive; Other: virtual technology - low interactive; Other: non-colorectal cancer related module
Sponsors: University of Florida; National Cancer Institute (NCI)
Recruiting

Permalink for 'Whole Body Vibration for the Improvement of Health and Functioning in Participants With Chemotherapy-Induced Peripheral Neuropathy'

Whole Body Vibration for the Improvement of Health and Functioning in Participants With Chemotherapy-Induced Peripheral Neuropathy

Posted: November 20th, 2019, 3:00am GMT

Conditions: Chemotherapy-Induced Peripheral Neuropathy; Hematopoietic and Lymphoid Cell Neoplasm; Malignant Solid Neoplasm
Interventions: Behavioral: Whole Body Vibration
Sponsors: OHSU Knight Cancer Institute; Oregon Health and Science University
Completed

Stereotactic Magnetic Resonance Guided Radiation Therapy

Posted: October 3rd, 2019, 2:00am GMT

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

The Registry of Oncology Outcomes Associated With Testing and Treatment

Posted: July 22nd, 2019, 2:00am GMT

Conditions: Adenocarcinoma; Adenocystic Carcinoma; Anal Cancer; Appendix Cancer; Brain Tumor; Glioblastoma; Astrocytoma; Bile Duct Cancer; Cholangiocarcinoma; Bladder Cancer; Bone Cancer; Synovial Sarcoma; Chondrosarcoma; Liposarcoma; Sarcoma, Kaposi; Sarcoma,Soft Tissue; Sarcoma; Osteosarcoma; CNS Cancer; Brain Stem Neoplasms; Breast Cancer; Cervical Cancer; Colorectal Cancer; Rectal Cancer; Colon Cancer; Esophageal Cancer; Esophagus Cancer; Cancer of Colon; Pancreatic Cancer; Cancer of Pancreas; Testis Cancer; Testicular Cancer; Ureter Cancer; Renal Cell Carcinoma; Kidney Cancer; Gestational Trophoblastic Tumor; Head and Neck Neoplasms; Parotid Tumor; Larynx Cancer; Tongue Cancer; Pharynx Cancer; Salivary Gland Cancer; Acute Myeloid Leukemia; Chronic Myeloid Leukemia; Acute Lymphoblastic Leukemia; Multiple Myeloma; Non Hodgkin Lymphoma; Carcinoid Tumor; Lung Cancer; Neuroendocrine Tumors; Mesothelioma; Thyroid Cancer; Parathyroid Neoplasms; Adrenal Cancer; Small Bowel Cancer; Stomach Cancer; Liver Cancer; Hepatic Cancer; Melanoma; Skin Cancer; Unknown Primary Tumors; Uterine Cancer; Fallopian Tube Cancer; Ovarian Cancer; Prostate Cancer; Vaginal Cancer; Penile Cancer; Vulvar Cancer; Waldenstrom Macroglobulinemia; Cancer, Advanced; Thymus Cancer; Nasopharyngeal Carcinoma; Multiple Endocrine Neoplasia; Pheochromocytoma; Small Cell Carcinoma; Pulmonary Carcinoma
Interventions: Diagnostic Test: Biomarker Testing (L); Drug: Systemic Treatment (T); Other: Patient Reported Outcomes (P)
Sponsors: Taproot Health
Recruiting

Erector Spinae Block vs. Placebo Block Study

Posted: June 7th, 2019, 2:00pm GMT

Conditions: Breast Cancer; Nerve Block; Regional Anesthesia; Neuromuscular Blockade
Interventions: Procedure: Erector spinae plane block; Procedure: Placebo Block
Sponsor: Women's College Hospital
Not yet recruiting

Relative Contributions of Predictors of Hyperandrogenism in Older vs. Young Women With PCOS

Posted: April 5th, 2019, 2:00am GMT

Conditions: Polycystic Ovary Syndrome
Interventions: Drug: ACTH; Drug: rhCG
Sponsors: University of Virginia
Recruiting

Inositol Supplementation to Treat PCOS (INSUPP-PCOS)

Posted: March 6th, 2019, 3:00am GMT

Conditions: Polycystic Ovary Syndrome; Anovulation; Hyperandrogenism; Insulin Resistance; Glucose Intolerance; Metabolic Complication
Interventions: Other: Placebo; Drug: Inositol
Sponsors: Milton S. Hershey Medical Center; National Center for Complementary and Integrative Health (NCCIH)
Recruiting

Stereotactic Ablative Radiotherapy for Comprehensive Treatment of Oligometastatic (1-3 Metastases) Cancer

Posted: March 5th, 2019, 3:00pm GMT

Condition: Metastatic Tumors
Interventions: Radiation: palliative radiotherapy; Radiation: Stereotactic ablative radiotherapy
Sponsors: British Columbia Cancer Agency; London Regional Cancer Program, Canada; The Alfred; Beacon Hospital, Ireland; Cancer Trials Ireland; Cancer Research UK Edinburgh Centre; Bon Secours Cork Cancer Centre; UPMC Hillman Cancer Centre; Beatson West of Scotland Cancer Centre; Tom Baker Cancer Centre; Walker Family Cancer Centre; Riverina Cancer Care Centre
Recruiting

Long-Term Follow-Up of Survivors of Pediatric Cushing Disease

Posted: February 6th, 2019, 3:00am GMT

Conditions: Cushing Disease
Sponsors: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Recruiting

Major immunophenotypic abnormalities in patients with primary adrenal insufficiency of different etiology

Fetched: December 5th, 2023, 5:00am GMT by Hanna F Nowotny

Front Immunol. 2023 Nov 15;14:1275828. doi: 10.3389/fimmu.2023.1275828. eCollection 2023.

ABSTRACT

INTRODUCTION: Patients with primary adrenal insufficiency (PAI) suffer from increased risk of infection, adrenal crises and have a higher mortality rate. Such dismal outcomes have been inferred to immune cell dysregulation because of unphysiological cortisol replacement. As the immune landscape of patients with different types of PAI has not been systematically explored, we set out to immunophenotype PAI patients with different causes of glucocorticoid (GC) deficiency.

METHODS: This cross-sectional single center study includes 28 patients with congenital adrenal hyperplasia (CAH), 27 after bilateral adrenalectomy due to Cushing's syndrome (BADx), 21 with Addison's disease (AD) and 52 healthy controls. All patients with PAI were on a stable GC replacement regimen with a median dose of 25 mg hydrocortisone per day. Peripheral blood mononuclear cells were isolated from heparinized blood samples. Immune cell subsets were analyzed using multicolor flow cytometry after four-hour stimulation with phorbol myristate acetate and ionomycin. Natural killer (NK-) cell cytotoxicity and clock gene expression were investigated.

RESULTS: The percentage of T helper cell subsets was downregulated in AD patients (Th1 p = 0.0024, Th2 p = 0.0157, Th17 p < 0.0001) compared to controls. Cytotoxic T cell subsets were reduced in AD (Tc1 p = 0.0075, Tc2 p = 0.0154) and CAH patients (Tc1 p = 0.0055, Tc2 p = 0.0012) compared to controls. NKCC was reduced in all subsets of PAI patients, with smallest changes in CAH. Degranulation marker CD107a expression was upregulated in BADx and AD, not in CAH patients compared to controls (BADx p < 0.0001; AD p = 0.0002). In contrast to NK cell activating receptors, NK cell inhibiting receptor CD94 was upregulated in BADx and AD, but not in CAH patients (p < 0.0001). Although modulation in clock gene expression could be confirmed in our patient subgroups, major interindividual-intergroup dissimilarities were not detected.

DISCUSSION: In patients with different etiologies of PAI, distinct differences in T and NK cell-phenotypes became apparent despite the use of same GC preparation and dose. Our results highlight unsuspected differences in immune cell composition and function in PAI patients of different causes and suggest disease-specific alterations that might necessitate disease-specific treatment.

PMID:38045693 | PMC:PMC10690587 | DOI:10.3389/fimmu.2023.1275828

Permalink for 'Risk factors of local control in adrenal metastases treated by stereotactic body radiation therapy - a systematic review and meta-analysis'

Risk factors of local control in adrenal metastases treated by stereotactic body radiation therapy - a systematic review and meta-analysis

Fetched: December 5th, 2023, 5:00am GMT by Xuehong Liao

Front Oncol. 2023 Nov 17;13:1193574. doi: 10.3389/fonc.2023.1193574. eCollection 2023.

ABSTRACT

PURPOSE: This study is aimed to explore risk factors affect the therapy outcomes of adrenal metastases (AM) for stereotactic body radiation therapy (SBRT) and guide clinical dose selection.

METHODS AND MATERIALS: PubMed, Embase and Web of Science were searched in September 22, 2022 in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). Subgroup analysis and meta-regression were used to search for sources of heterogeneity and identify risky outcomes factors. Publication bias test and sensitivity analysis were also conducted.

RESULTS: Thirty-three studies with full text from 2009 to 2022 about AM with SBRT on 1483 patients were included. Pooled 1- and 2-year local control (LC) and overall survival(OS) were 81.7% (95% confidence interval [CI], 75.6%-86.5%), 62.8% (95% CI, 53.8%-71.8%), 67.4% (95%CI, 61.8%-73.1%) and 46.5% (95%CI, 40.4%-52.6%), respectively. Biological effective dose (BED, α/β=10Gy) and dose per fraction affected 1-year LC (Qm=23.89, 15.10; P<0.0001, 0.0001). In the range of 60-80Gy (BED10), the group of dose per fraction ≥ 9Gy achieved the excellent 1-year LC (< 9Gy: ≥ 9Gy =78%, 91%; χ² = 10.16, P = 0.001). Tracking technology significantly affected 1- and 2-year OS (Qm = 5.73, 8.75; P = 0.017, 0.003) and high tracking adoption group showed excellent 1- and 2- year OS (78.7% [95%CI, 68.6%- 88.9%]; and 62.9% [95%CI, 53.1%-72.7%]).

CONCLUSION: Increasing the dose per fraction appropriately may help control locally AM lesious. Tracking technology might contribute to improve survival of advanced patients with AM. But these results need prospective studies to verify them.

PMID:38045003 | PMC:PMC10691549 | DOI:10.3389/fonc.2023.1193574

Permalink for 'Efficacy and safety of corticosteroids, hyaluronic acid, and PRP and combination therapy for knee osteoarthritis: a systematic review and network meta-analysis'

Efficacy and safety of corticosteroids, hyaluronic acid, and PRP and combination therapy for knee osteoarthritis: a systematic review and network meta-analysis

Fetched: December 5th, 2023, 5:00am GMT by Xiaochen Qiao

BMC Musculoskelet Disord. 2023 Nov 30;24(1):926. doi: 10.1186/s12891-023-06925-6.

ABSTRACT

OBJECTIVE: There are many injectable treatments for knee osteoarthritis with different characteristics and effects, the aim is to understand which one can lead to better and safer results.

METHODS: The PRISMA principles were followed when doing the literature search. Web of Science databases, Embase, the Cochrane Library, PubMed, and the Wanfang database were searched to identified randomized controlled trials that assessed the efficacy of corticosteroids (CSC), platelet-rich plasma (PRP), hyaluronic acid (HA), and combination therapy in treating KOA. Risk of bias was assessed using the relevant Cochrane tools (version 1.0). The outcome measure included the visual analog scale (VAS) score, the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) score, and treatment-related adverse events. The network meta-analysis was performed using STATA17 software and a Bayesian stratified random effects model.

RESULTS: Network meta-analysis using the Bayesian random-effects model revealed 35 studies with 3104 participants. PRP showed the best WOMAC score at a 3-month follow-up, followed by PRP + HA, HA, placebo, and CSC; PRP + HA scored the highest VAS, followed by PRP, CSC, HA, and placebo. PRP, CSC, HA, and placebo had the highest WOMAC scores six months following treatment; PRP + HA showed the best VAS scores. PRP showed the best WOMAC score at 12 months, followed by PRP + HA, HA, placebo, and CSC; The best VAS score was obtained with PRP, followed by PRP + HA, HA, and CSC. No therapy demonstrated a rise in adverse events linked to the treatment in terms of safety.

CONCLUSIONS: The current study found that PRP and PRP + HA were the most successful in improving function and alleviating pain after 3, 6, and 12 months of follow-up. CSC, HA, PRP, and combination therapy did not result in an increase in the incidence of treatment-related side events as compared to placebo.

PMID:38037038 | PMC:PMC10687893 | DOI:10.1186/s12891-023-06925-6

False-positive results for pheochromocytoma associated with norepinephrine reuptake blockade

Fetched: December 5th, 2023, 5:00am GMT by Robin Schürfeld

Endocr Relat Cancer. 2023 Dec 1;31(1):e230063. doi: 10.1530/ERC-23-0063. Print 2024 Jan 1.

ABSTRACT

Measurements of plasma metanephrines and methoxytyramine provide a sensitive test for diagnosis of pheochromocytoma/paraganglioma. False-positive results remain a problem, particularly in patients taking norepinephrine reuptake-blocking drugs. Therefore, in this retrospective observational study, we measured plasma metanephrines and methoxytyramine in 61 patients taking norepinephrine reuptake blockers (tricyclic antidepressants or serotonin-norepinephrine reuptake inhibitors) and 17 others taking selective serotonin reuptake inhibitors, all without pheochromocytoma/paraganglioma. We highlight a singular case with strongly elevated plasma normetanephrine and methoxytyramine concentrations associated with norepinephrine reuptake blockade. Data were compared to results from 252 and 1804 respective patients with and without tumors. Plasma normetanephrine was 40% higher (P < 0.0001) in patients on norepinephrine reuptake blockers and methoxytyramine was 127% higher (P = 0.0062) in patients taking tricyclic antidepressants compared to patients not taking uptake blockers and without tumors. The corresponding false-positive rates rose (P < 0.0001) from 4.8% to 23.0% for normetanephrine and from 0.9% to 28.6% for methoxytyramine. Selective serotonin reuptake inhibitors did not increase plasma concentrations of metabolites. In the highlighted case, plasma normetanephrine and methoxytyramine were elevated more than six times above upper reference limits. A pheochromocytoma/paraganglioma, however, was excluded by functional imaging. All biochemical test results normalized after discontinuation of norepinephrine reuptake blockers. These findings clarify that norepinephrine reuptake blockers usually result in mild elevations of normetanephrine and methoxytyramine that, nevertheless, significantly increase the number of false-positive results. There can, however, be exceptions where increases in normetanephrine and methoxytyramine reach pathological levels. Such exceptions may reflect failure of centrally mediated sympathoinhibition that normally occurs with the norepinephrine reuptake blockade.

PMID:37955319 | DOI:10.1530/ERC-23-0063

Permalink for 'Machine Learning Model with Computed Tomography Radiomics and Clinicobiochemical Characteristics Predict the Subtypes of Patients with Primary Aldosteronism'

Machine Learning Model with Computed Tomography Radiomics and Clinicobiochemical Characteristics Predict the Subtypes of Patients with Primary Aldosteronism

Fetched: December 3rd, 2023, 5:00am GMT by Po-Ting Chen

Acad Radiol. 2023 Dec 1:S1076-6332(23)00549-4. doi: 10.1016/j.acra.2023.10.015. Online ahead of print.

ABSTRACT

RATIONALE AND OBJECTIVES: Adrenal venous sampling (AVS) is the primary method for differentiating between primary aldosterone (PA) subtypes. The aim of study is to develop prediction models for subtyping of patients with PA using computed tomography (CT) radiomics and clinicobiochemical characteristics associated with PA.

MATERIALS AND METHODS: This study retrospectively enrolled 158 patients with PA who underwent AVS between January 2014 and March 2021. Neural network machine learning models were developed using a two-stage analysis of triple-phase abdominal CT and clinicobiochemical characteristics. In the first stage, the models were constructed to classify unilateral or bilateral PA; in the second stage, they were designed to determine the predominant side in patients with unilateral PA. The final proposed model combined the best-performing models from both stages. The model's performance was evaluated using repeated stratified five-fold cross-validation. We employed paired t-tests to compare its performance with the conventional imaging evaluations made by radiologists, which categorize patients as either having bilateral PA or unilateral PA on one side.

RESULTS: In the first stage, the integrated model that combines CT radiomic and clinicobiochemical characteristics exhibited the highest performance, surpassing both the radiomic-alone and clinicobiochemical-alone models. It achieved an accuracy and F1 score of 80.6% ± 3.0% and 74.8% ± 5.2% (area under the receiver operating curve [AUC] = 0.778 ± 0.050). In the second stage, the accuracy and F1 score of the radiomic-based model were 88% ± 4.9% and 81.9% ± 6.2% (AUC=0.831 ± 0.087). The proposed model achieved an accuracy and F1 score of 77.5% ± 3.9% and 70.5% ± 7.1% (AUC=0.771 ± 0.046) in subtype diagnosis and lateralization, surpassing the accuracy and F1 score achieved by radiologists' evaluation (p < .05).

CONCLUSION: The proposed machine learning model can predict the subtypes and lateralization of PA. It yields superior results compared to conventional imaging evaluation and has potential to supplement the diagnostic process in PA.

PMID:38042624 | DOI:10.1016/j.acra.2023.10.015

Renal Function Evolution and Hypoaldosteronism Risk After Unilateral Adrenalectomy for Primary Aldosteronism

Fetched: December 2nd, 2023, 5:00am GMT by Nara L Queiroz

Horm Metab Res. 2023 Dec 1. doi: 10.1055/a-2221-3302. Online ahead of print.

ABSTRACT

Few studies demonstrated a percentage decrease in the estimated glomerular filtration rate (eGFR) at a single time and the rate of hypoaldosteronism after adrenalectomy for primary aldosteronism (PA). To investigate the evolution of renal function and the hypoaldosteronism risk after adrenalectomy for PA. Aldosterone, renin, eGFR, and electrolyte levels were determined before and at 1 week, 1, 3 and 6 months after unilateral adrenalectomy in 94 PA patients (40 men and 54 women). The main outcome was the postoperative eGFR decline using analysis of covariance with the preoperative eGFR as a covariate. eGFR decreased during first postoperative week compared to 3 months before surgery. During the first 6 months, eGFR remained stable at similar levels to the first week after surgery. Age (p=0.001), aldosterone levels (p=0.021) and eGFR 3 months before surgery (p<0.0001) had a significant correlation with eGFR during first postoperative week. High aldosterone levels at diagnosis were correlated with decline in renal function in the univariate model (p=0.033). In the multivariate analysis, aldosterone levels at diagnosis had a tendency to be an independent predictor of renal function after surgery (p=0.059). Postoperative biochemical hypoaldosteronism was diagnosed in 48% of the cases after adrenalectomy, but prolonged hyperkalemia occurred in only 4 cases (4.5%). Our findings showed a decrease of eGFR after unilateral adrenalectomy for PA. Additionally, aldosterone levels at diagnosis correlated with postoperative renal function. Postoperative biochemical hypoaldosteronism occurred in almost half of the patients, but prolonged hyperkalemia with fludrocortisone replacement was less frequent.

PMID:38040032 | DOI:10.1055/a-2221-3302

Laparoscopic surgery for adrenocortical carcinoma: Estimating the risk of margin-positive resection

Fetched: December 2nd, 2023, 5:00am GMT by Kendyl Carlisle

J Surg Oncol. 2023 Nov 30. doi: 10.1002/jso.27544. Online ahead of print.

ABSTRACT

BACKGROUND: Over recent years, there has been increasing adoption of minimally invasive surgery (MIS) in the treatment of adrenocortical carcinoma (ACC). However, MIS has been associated with noncurative resection and locoregional recurrence. We aimed to identify risk factors for margin-positivity among patients who undergo MIS resection for ACC. We hypothesized that a simple nomogram can accurately identify patients most suitable for curative MIS resection.

METHODS: Curative-intent resections for ACC were identified through the National Cancer Database spanning 2010-2018. Trends in MIS utilization were reported using Pearson correlation coefficients. Factors associated with margin-positive resection were identified among preoperatively available variables using multivariable logistic regression, then incorporated into a predictive model. Model quality was cross validated using an 80% training data set and 20% test data set.

RESULTS: Among 1260 ACC cases, 38.6% (486) underwent MIS resection. MIS utilization increased over time at nonacademic centers (R = 0.818, p = 0.007), but not at academic centers (R = 0.009, p = 0.982). Factors associated with margin-positive MIS resection were increasing age, nonacademic center (odds ratio [OR]: 1.8, p = 0.006), cT3 (OR: 4.7, p < 0.001) or cT4 tumors (OR: 14.6, p < 0.001), and right-sided tumors (OR: 2.0, p = 0.006). A predictive model incorporating these four factors produced favorable c-statistics of 0.75 in the training data set and 0.72 in the test data set. A pragmatic nomogram was created to enable bedside risk stratification.

CONCLUSIONS: An increasing proportion of ACC are resected via minimally invasive operations, particularly at nonacademic centers. Patient selection based on a few key factors can minimize the risk of noncurative surgery.

PMID:38037311 | DOI:10.1002/jso.27544

Response to Letter to the Editor regarding 'Risk of complications after core needle biopsy in pheochromocytoma/paraganglioma'

Fetched: December 2nd, 2023, 5:00am GMT by Liang Zhang

Endocr Relat Cancer. 2023 Nov 30;31(1):e230271. doi: 10.1530/ERC-23-0271. Print 2024 Jan 1.

NO ABSTRACT

PMID:38031994 | DOI:10.1530/ERC-23-0271

Core needle biopsy in pheochromocytoma/paraganglioma: should it be considered?

Fetched: December 2nd, 2023, 5:00am GMT by Gergely Huszty

Endocr Relat Cancer. 2023 Nov 30;31(1):e230220. doi: 10.1530/ERC-23-0220. Print 2024 Jan 1.

NO ABSTRACT

PMID:38031993 | DOI:10.1530/ERC-23-0220

Adrenocortical carcinoma - 12-year observation period in a single centre. Case report with literature review

Fetched: December 2nd, 2023, 5:00am GMT by Patrycja Dasiewicz

Pediatr Endocrinol Diabetes Metab. 2023;29(3):202-208. doi: 10.5114/pedm.2023.132131.

ABSTRACT

BACKGROUND: Adrenocortical carcinoma (ACC) accounts for 0.2% of childhood malignancies. The most common symptom in children is rapidly progressive androgenization. Herein, we report a case of a patient with symptoms of hypercortisolaemia and androgenization, who was diagnosed with ACC.

CASE PRESENTATION: In a 10-year-old patient with ACC the course of the disease was complicated by 3 recurrences. She was treated with surgery, chemo-, and radiotherapy. Currently, 8 years after the end of treatment, there have been no signs of recurrence.

CONCLUSIONS: A patient after ACC treatment requires regular check-ups and long-term observation. Constant supervision enables early diagnosis of disease recurrence, and the use of treatment improves the prognosis.

PMID:38031835 | PMC:PMC10679906 | DOI:10.5114/pedm.2023.132131

Permalink for 'Clinical characteristics of a large familial cohort with Medullary thyroid cancer and germline Cys618Arg RET mutation in an Israeli multicenter study'

Clinical characteristics of a large familial cohort with Medullary thyroid cancer and germline Cys618Arg RET mutation in an Israeli multicenter study

Fetched: December 2nd, 2023, 5:00am GMT by Rachel Chava Rosenblum

Front Endocrinol (Lausanne). 2023 Oct 30;14:1268193. doi: 10.3389/fendo.2023.1268193. eCollection 2023.

ABSTRACT

OBJECTIVE: To determine genealogical, clinical and pathological characteristics of a cohort with Cys618Arg mutation from an Israeli multicenter MTC study.

METHODS: Retrospective database analysis examining RET mutations and comparing Cys618Arg and Cys634Arg/Thr/Tyr subgroups.

RESULTS: Genetic testing was performed in 131/275 MTC patients (47.6%). RET mutations were found in 50/131 (38.2%), including Cys618Arg (28/50 cases,56%), and Cys634Arg/Thr/Tyr (15/50,30%). Through genealogical study, 31 MTC patients were found descendants of one family of Jewish Moroccan descent, accounting for 27/28 patients with documented Cys618Arg mutation and 4 patients without available genetic testing. Familial Cys618Arg cases (n=31) and Cys634Arg/Thr/Tyr cases (n=15, from 6 families) were compared. Although surgical age was similar (25.7 vs 31.3 years, p=0.19), the Cys618Arg group had smaller tumors (8.9mm vs 18.5mm, p=0.004) and lower calcitonin levels (33.9 vs 84.5 X/ULN, p=0.03). Youngest ages at MTC diagnosis were 8 and 3 years in Cys618Arg and Cys634Arg/Thr/Tyr cohorts, respectively. Long-term outcome was similar between groups. The Cys618Arg cohort had lower rates of pheochromocytoma (6.5% vs 53.3%, p=0.001) and primary hyperparathyroidism (3.2% vs 33.3%, p=0.01).

CONCLUSION: This is the first description of RET mutation distribution in Israel. Of 131 tested MTC patients, Cys618Arg was the predominant mutation. To the best of our knowledge, this is the largest cohort of Cys618Arg mutation described. For Cys618Arg and Cys634Arg/Thr/Tyr cohorts, MTC was diagnosed earlier than expected, likely due to familial genetic screening, and MTC outcomes were similar between groups. International studies are necessary to further characterize the clinical features of Cys618 mutations due to their relative rarity.

PMID:38027168 | PMC:PMC10646927 | DOI:10.3389/fendo.2023.1268193

Bilateral co-secretory lesions presenting with coexisting Cushing syndrome and primary aldosteronism: a case report

Fetched: December 1st, 2023, 5:00am GMT by Hongjiao Gao

BMC Endocr Disord. 2023 Nov 29;23(1):263. doi: 10.1186/s12902-023-01454-8.

ABSTRACT

BACKGROUND: There is an increasing number of cases of aldosterone- and cortisol-producing adenomas (A/CPAs) reported in the context of primary aldosteronism (PA). Most of these patients have PA complicated with subclinical Cushing's syndrome; cases of apparent Cushing's syndrome (CS) complicated with aldosteronism are less reported. However, Co-secretory tumors were present in the right adrenal gland, a cortisol-secreting adenoma and an aldosterone-producing nodule (APN) were present in the left adrenal gland, and aldosterone-producing micronodules (APMs) were present in both adrenal glands, which has not been reported. Here, we report such a case, offering profound insight into the diversity of clinical and pathological features of this disease.

CASE PRESENTATION: The case was a 45-year-old female from the adrenal disease diagnosis and treatment centre in West China Hospital of Sichuan University. The patient presented with hypertension, moon-shaped face, central obesity, fat accumulation on the back of the neck, disappearance of cortisol circadian rhythm, ACTH < 5 ng/L, failed elevated cortisol inhibition by dexamethasone, orthostatic aldosterone/renin activity > 30 (ng/dL)/(ng/mL/h), and plasma aldosterone concentration > 10 ng/dL after saline infusion testing. Based on the above, she was diagnosed with non-ACTH-dependent CS complicated with PA. Adrenal vein sampling showed no lateralization for cortisol and aldosterone secretion in the bilateral adrenal glands. The left adrenocortical adenoma was removed by robot-assisted laparoscopic resection. However, hypertension, fatigue and weight gain were not alleviated after surgery; additionally, purple striae appeared in the lower abdomen, groin area and inner thigh, accompanied by systemic joint pain. One month later, the right adrenocortical adenoma was also removed. CYP11B1 were expressed in the bilateral adrenocortical adenomas, and CYP11B2 was also expressed in the right adrenocortical adenomas. APN existed in the left adrenal gland and APMs in the adrenal cortex adjacent to bilateral adrenocortical adenomas. After another surgery, her serum cortisol and plasma aldosterone returned to normal ranges, except for slightly higher ACTH.

CONCLUSIONS: This case suggests that it is necessary to assess the presence of PA, even in CS with apparent symptoms. As patients with CS and PA may have more complicated adrenal lesions, more data are required for diagnosis.

PMID:38017509 | PMC:PMC10685549 | DOI:10.1186/s12902-023-01454-8

Impact of overnight 1 mg dexamethasone on vascular function in patients with nonfunctioning adrenal adenomas

Fetched: December 1st, 2023, 5:00am GMT by Shinji Kishimoto

Sci Rep. 2023 Nov 28;13(1):20975. doi: 10.1038/s41598-023-48295-y.

ABSTRACT

The purpose of this study was to evaluate the effects of administration of overnight 1 mg dexamethasone on vascular function in patients with nonfunctioning adrenal adenomas (NFA). Flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID) were measured to assess vascular function in 22 patients with NFA who had hypertension and/or diabetes mellitus (DM) and 272 patients without adrenal incidentalomas who had hypertension and/or DM (control patients with hypertension and/or DM). FMD and NID were measured in the morning before and after administration of 1 mg of dexamethasone at 2300 h in 18 patients with NFA. There were no significant differences in FMD and NID between control patients with hypertension and/or DM and patients with NFA who had hypertension and/or DM (3.4 ± 2.8% vs. 2.9 ± 1.9% and 11.5 ± 5.7% vs. 11.4 ± 4.3%, P = 0.46, and P = 0.99, respectively). There were no significant differences in vascular function between control patients with hypertension and/or DM and patients with NFA who had hypertension and/or DM even after adjustment for cardiovascular risk factors. Overnight 1 mg dexamethasone increased FMD from 2.4 ± 1.9% to 5.3 ± 3.2% (P < 0.01) and increased NID from 12.1 ± 4.2% to 14.0 ± 2.8% (P < 0.01) in patients with NFA. The overnight 1 mg dexamethasone suppression test does not impair FMD and NID in patients with NFA. Decreases in circulating levels of cortisol may improve vascular function.Clinical Trial Registration: This study was approved by principal authorities and ethical issues in Japan (URL for Clinical Trial: [www.umin.ac.jp] Registration Number for Clinical Trial: UMIN000039512).

PMID:38017255 | PMC:PMC10684497 | DOI:10.1038/s41598-023-48295-y

Screening of Natural Compounds for CYP11A1 Stimulation Against Cell Renal Cell Carcinoma

Fetched: December 1st, 2023, 5:00am GMT by Hien Thi My Ong

Biol Proced Online. 2023 Nov 30;25(1):31. doi: 10.1186/s12575-023-00225-y.

ABSTRACT

BACKGROUND: Renal cancer therapies are challenging owing to the extensive spreading of this cancer to other organs and its ability to pose resistance to current medications. Therefore, drugs targeting novel targets are urgently required to overcome these challenges. The cholesterol side-chain cleavage enzyme (CYP11A1) is closely associated with steroidogenesis, and its downregulation is linked to adrenal dysfunction and several types of carcinoma. We previously found that overexpression of CYP11A1 inhibited epithelial-mesenchymal transition and induced G2/M arrest in the kidney cancer Caki-1 cell line. In this context, natural compounds that exhibit potent CYP11A1 stimulation activity can be promising therpaeutic agents for kidney cancer.

METHODS: We screened a panel of 1374 natural compounds in a wound-healing assay using CYP11A1-transfected Caki-1 cells. Of these, 167 promising biologically active compounds that inhibited cancer cell migration by more than 75% were selected, and their half-maximal inhibitory concentrations (IC50) were determined. The IC50 of 159 compounds was determined and 38 compounds with IC50 values less than 50 µM were selected for further analysis. Steroid hormones (cholesterol and pregnenolone) levels in cells treated with the selected compounds were quantitated using LC-MS/MS to determine their effect on CYP11A1 activity. Western blotting for CYP11A1, autophagy signaling proteins, and ferroptosis regulators were performed to ivestigate the mechanisms underlying the action of the selected compounds.

RESULTS: We screened five promising natural lead compounds that inhibited cancer cell proliferation after three screening steps. The IC50 of these compounds was determined to be between 5.9 and 14.6 μM. These candidate compounds increased the expression of CYP11A1 and suppressed cholesterol levels while increasing pregnenolone levels, which is consistent with the activation of CYP11A1. Our results showed that CYP11A1 activation inhibited the migration of cancer cells, promoted ferroptosis, and triggered autophagy signaling.

CONCLUSIONS: This study indicates that the CYP11A1-overexpressing Caki-1 cell line is useful for screening drugs against kidney cancer. The two selected compounds could be utilized as lead compounds for anticancer drug discovery, and specifically for the development of antirenal cancer medication.

PMID:38036976 | PMC:PMC10687993 | DOI:10.1186/s12575-023-00225-y

Permalink for 'Differentiating adrenal metastases from benign lesions with multiphase CT imaging: Deep learning could play an active role in assisting radiologists'

Differentiating adrenal metastases from benign lesions with multiphase CT imaging: Deep learning could play an active role in assisting radiologists

Fetched: November 30th, 2023, 5:00am GMT by Changyi Ma

Eur J Radiol. 2023 Dec;169:111169. doi: 10.1016/j.ejrad.2023.111169. Epub 2023 Nov 7.

ABSTRACT

OBJECTIVES: To develop and externally validate multiphase CT-based deep learning (DL) models for differentiating adrenal metastases from benign lesions.

MATERIALS AND METHODS: This retrospective two-center study included 1146 adrenal lesions from 1059 patients who underwent multiphase CT scanning between January 2008 and March 2021. The study encompassed 564 surgically confirmed adenomas, along with 135 benign lesions and 447 metastases confirmed by observation. DL models based on multiphase CT images were developed, validated and tested. The diagnostic performance of the classification models, imaging phases and radiologists with or without DL were compared using accuracy (ACC) and receiver operating characteristic (ROC) curves. Integrated discrimination improvement (IDI) analysis and the DeLong test were used to compare the area under the curve (AUC) among models. Decision curve analysis (DCA) was used to assess the clinical usefulness of the predictive models.

RESULTS: The DL signature based on LASSO (DLSL) had a higher AUC than that of the other classification models (IDI > 0, P < 0.05). Furthermore, the precontrast phase (PCP)-based DLSL performed best in the independent external validation (AUC = 0.881, ACC = 82.9 %) and clinical test cohorts (AUC = 0.790, ACC = 70.4 %), outperforming DLSL based on the other single-phase or three-phase images (IDI > 0, P < 0.05). DCA demonstrated that PCP-based DLSL provided a higher net benefit (0.01-0.95). The diagnostic performance led to statistically significant improvements when radiologists incorporated the DL model, with the AUC improving by 0.056-0.159 and the ACC improving by 0.069-0.178 (P < 0.05).

CONCLUSION: The DL model based on PCP CT images performed acceptably in differentiating adrenal metastases from benign lesions, and it may assist radiologists in accurate tumor staging for patients with a history of extra-adrenal malignancy.

PMID:37956572 | DOI:10.1016/j.ejrad.2023.111169

Responses to systemic therapy in metastatic pheochromocytoma/paraganglioma: a retrospective multicenter cohort study

Fetched: November 30th, 2023, 5:00am GMT by Alessa Fischer

Eur J Endocrinol. 2023 Nov 8;189(5):546-565. doi: 10.1093/ejendo/lvad146.

ABSTRACT

OBJECTIVE: The therapeutic options for metastatic pheochromocytomas/paragangliomas (mPPGLs) include chemotherapy with cyclophosphamide/vincristine/dacarbazine (CVD), temozolomide monotherapy, radionuclide therapies, and tyrosine kinase inhibitors such as sunitinib. The objective of this multicenter retrospective study was to evaluate and compare the responses of mPPGLs including those with pathogenic variants in succinate dehydrogenase subunit B (SDHB), to different systemic treatments.

DESIGN: This is a retrospective analysis of treatment responses of mPPGL patients (n = 74) to systemic therapies.

METHODS: Patients with mPPGLs treated at 6 specialized national centers were selected based on participation in the ENSAT registry. Survival until detected progression (SDP) and disease-control rates (DCRs) at 3 months were evaluated based on imaging reports.

RESULTS: For the group of patients with progressive disease at baseline (83.8% of 74 patients), the DCR with first-line CVD chemotherapy was 75.0% (n = 4, SDP 11 months; SDHB [n = 1]: DCR 100%, SDP 30 months), with somatostatin peptide receptor-based radionuclide therapy (PPRT) 85.7% (n = 21, SDP 17 months; SDHB [n = 10]: DCR 100%, SDP 14 months), with 131I-meta-iodobenzylguanidine (131I-MIBG) 82.6% (n = 23, SDP 43 months; SDHB [n = 4]: DCR 100%, SDP 24 months), with sunitinib 100% (n = 7, SDP 18 months; SDHB [n = 3]: DCR 100%, SDP 18 months), and with somatostatin analogs 100% (n = 4, SDP not reached). The DCR with temozolomide as second-line therapy was 60.0% (n = 5, SDP 10 months; SDHB [n = 4]: DCR 75%, SDP 10 months).

CONCLUSIONS: We demonstrate in a real-life clinical setting that all current therapies show reasonable efficacy in preventing disease progression, and this is equally true for patients with germline SDHB mutations.

PMID:37949483 | DOI:10.1093/ejendo/lvad146

Robotic-Assisted Partial Nephrectomy for Kidney Cancer: A Health Technology Assessment

Fetched: November 30th, 2023, 5:00am GMT by Ontario Health (Quality)

Ont Health Technol Assess Ser. 2023 Oct 10;23(7):1-77. eCollection 2023.

ABSTRACT

BACKGROUND: Robotic-assisted surgery has been used in Ontario hospitals for over a decade, but there is no public funding for the robotic systems or the disposables required to perform robotic-assisted surgeries ("robotics disposables"). We conducted a health technology assessment of robotic-assisted partial nephrectomy for the treatment of kidney cancer (RAPN). Nephrectomy may be radical (the surgical removal of an entire kidney, nearby adrenal gland and lymph nodes, and other surrounding tissue) or partial (the surgical removal of part of a kidney or a kidney tumour). Partial nephrectomy is the gold standard surgical treatment for early kidney cancer. Our assessment included an evaluation of the effectiveness, safety, and cost-effectiveness of RAPN, as well as the 5-year budget impact for the Ontario Ministry of Health of publicly funding RAPN. It also looked at the experiences, preferences, and values of people with kidney cancer, as well as those of health care professionals who provide surgical treatment for kidney cancer.

METHODS: We performed a systematic literature search of the clinical evidence to retrieve systematic reviews and selected and reported results from five reviews that were recent and relevant to our research questions. We used the Risk of Bias in Systematic Reviews (ROBIS) tool to assess the risk of bias of each included systematic review. We assessed the quality of the body of evidence reported in the selected reviews according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic economic literature search. We also analyzed the 5-year budget impact of publicly funding robotics disposables for RAPN for people with kidney cancer in Ontario. To contextualize the potential value of RAPN for people with kidney cancer, we spoke with people with lived experience of kidney cancer who had undergone either open or robotic-assisted nephrectomy, and we spoke with urologic surgeons who perform nephrectomy.

RESULTS: We included five systematic reviews in the clinical evidence review. Low-quality evidence from observational studies suggests that compared with open or laparoscopic partial nephrectomy, RAPN may decrease estimated blood loss, shorten length of hospital stay, and reduce complications (All GRADEs: Low). We identified five studies that met the inclusion criteria of our economic literature review. Most included economic studies found robotic-assisted surgical procedures to be more costly than open and laparoscopic procedures; however, the results from these studies were not applicable to the Ontario context. Assuming a moderate increase in the volume of RAPN procedures, our reference case analysis showed that the 5-year budget impact of publicly funding RAPN for people with kidney cancer would be $1.58 million. The budget impact analysis results were sensitive to surgical volume and the cost of robotics disposables. The people we spoke with who had lived experience of kidney cancer, as well as urologic surgeons, spoke favourably of RAPN and its perceived benefits over open and laparoscopic procedures.

CONCLUSIONS: RAPN may improve clinical outcomes and reduce complications. The cost-effectiveness of RAPN for people with kidney cancer is unknown. We estimate that the 5-year budget impact of publicly funding RAPN for people with kidney cancer would be $1.58 million. People we spoke with who had lived experience of kidney cancer and had undergone RAPN reported favourably on their experiences, particularly in terms of the quick recovery, short hospital stay, and minimal pain. Conversely, those who had undergone an open procedure spoke of difficulties including pain, complications, and increased length of hospital stay. Surgeons emphasized the importance of RAPN being made available to people with kidney cancer because of the increased risks and complications associated with open partial nephrectomy.

PMID:38028531 | PMC:PMC10656046

Permalink for 'Hemoglobin albumin lymphocyte and platelet score and all-cause mortality in coronary heart disease: a retrospective cohort study of NHANES database'

Hemoglobin albumin lymphocyte and platelet score and all-cause mortality in coronary heart disease: a retrospective cohort study of NHANES database

Fetched: November 30th, 2023, 5:00am GMT by Yang Zheng

Front Cardiovasc Med. 2023 Nov 13;10:1241217. doi: 10.3389/fcvm.2023.1241217. eCollection 2023.

ABSTRACT

AIM: Anemia, inflammatory status, and malnutrition are all important factors in the prognosis of cardiovascular disease (CVD), and their interactions are also noteworthy. A recent scoring system, the hemoglobin albumin lymphocyte and platelet (HALP) score, combining multi-dimensional metrics, has been used in the prognoses of many diseases except coronary heart disease (CHD). Herein, this study aims to explore the association between HALP score and all-cause mortality in patients with CHD.

METHODS: Demographic and clinical data of adult patients with CHD were extracted from the National Health and Nutrition Examination Surveys (NHANES) database from 2003 to 2018 in this retrospective cohort study. Weighted univariate and multivariate COX proportional hazard models were used for covariates screening and exploration of the association between HALP score and all-cause mortality. The evaluation indexes were hazard ratios (ORs) and 95% confidence intervals (CIs). Kaplan-Meier (KM) curve and the receiver operator characteristic (ROC) curve were used to assess the predictive performance of HALP on CHD prognosis. In addition, subgroup analyses of age and congestive heart failure (CHF) were also performed.

RESULTS: Among the eligible patients, 657 died of all-cause mortality. After adjusting for the covariates including age, education level, PIR, marital status, smoking, physical activity, total energy intake, CHF, stroke, hypertension, DM, CKD, cancer or malignancy, monocyte, drug for CVD, treatment for anemia, anticoagulants drug, and adrenal cortical steroids, we found that HALP score was negatively associated with the risk of all-cause mortality [HR = 0.83, 95% CI: (0.74-0.93)]. Compared with patients with high HALP scores, those who had lower HALP scores seemed to have a higher risk of all-cause mortality (all P < 0.05). HALP score has a potential predictive value on CHD prognosis with an area under the curve (AUC) of 0.61. Furthermore, in patients aged <65 years, with or without CHF, a lower HALP score was also associated with a higher risk of all-cause mortality (all P < 0.05).

CONCLUSIONS: HALP score has a potential predictive value on CHD prognosis; however, the causal association between HALP score and mortality in patients with CHD needs further exploration.

PMID:38028472 | PMC:PMC10679332 | DOI:10.3389/fcvm.2023.1241217

Rare adrenal cavernous hemangioma: a case report highlighting diagnostic challenges

Fetched: November 30th, 2023, 5:00am GMT by Ryan Michael Antar

Front Surg. 2023 Nov 10;10:1293925. doi: 10.3389/fsurg.2023.1293925. eCollection 2023.

ABSTRACT

INTRODUCTION: Adrenal cavernous hemangiomas are rare benign vascular tumors that pose significant diagnostic challenges. Despite their benign nature, features overlapping with malignancies often complicate management decisions.

CASE PRESENTATION: A 64-year-old male presented with a 4.4 cm necrotic left adrenal mass discovered incidentally on imaging. His medical history included papillary thyroid carcinoma, with subsequent thyroidectomy and radioactive iodine ablation. Evaluations for hiccups revealed multiple lung nodules, hypertrophic cardiomyopathy, and anemia. Given the patient's previous cancer history, elevated aldosterone/renin ratio, and mass size, our multidisciplinary tumor board decided to proceed with a left adrenalectomy. Post-surgical pathology confirmed a diagnosis of adrenal cavernous hemangioma.

CONCLUSION: The occurrence of ambiguous adrenal mass with other pathologies, such as our patient's papillary thyroid carcinoma, complicates the diagnostic and therapeutic landscape. As demonstrated in our case, opting for surgery remains a viable solution for adrenal cavernous hemangiomas, especially for masses greater than 4 cm. Interdisciplinary collaboration, exemplified by our tumor board's decision-making process, is crucial for optimal management. This case underscores the need for a multifaceted approach when confronting adrenal masses with such diagnostic ambiguity.

PMID:38026486 | PMC:PMC10667707 | DOI:10.3389/fsurg.2023.1293925

Left anterior descending artery disease in a 27-year-old with multiple endocrine neoplasia, type 2A: A case report

Fetched: November 30th, 2023, 5:00am GMT by Mohammed Omar Al Salihi

SAGE Open Med Case Rep. 2023 Nov 16;11:2050313X231212095. doi: 10.1177/2050313X231212095. eCollection 2023.

ABSTRACT

Multiple endocrine neoplasia 2A is an autosomal dominant disease characterized by medullary thyroid cancer, pheochromocytoma, and primary hyperparathyroidism. Coronary artery disease is associated with the disorder, but the mechanism is unclear. A 27-year-old female presented with chest pain and palpitations. A left heart catheterization was performed and showed 80% stenosis of the left anterior descending artery. Imaging and workup also revealed primary hyperparathyroidism associated with a parathyroid adenoma and elevated serum and urine metanephrines and norepinephrines. A computed tomography of the abdomen revealed a large heterogeneous right adrenal mass measuring 7.9 cm × 6.8 cm × 8 cm consistent with a pheochromocytoma. The patient subsequently underwent adrenal mass resection and a complete thyroidectomy and parathyroidectomy. Early recognition and treatment of multiple endocrine neoplasia 2A can possibly reduce the risk of lethal heart disease in addition to the other associated endocrine disturbances.

PMID:38022857 | PMC:PMC10655645 | DOI:10.1177/2050313X231212095

Three Cases of Carney-Stratakis Syndrome: A Genetically Heterogeneous Disease

Fetched: November 30th, 2023, 5:00am GMT by Eduardo C Lobato

JCEM Case Rep. 2023 Nov 25;1(6):luad139. doi: 10.1210/jcemcr/luad139. eCollection 2023 Nov.

ABSTRACT

Carney-Stratakis syndrome (CSS) is an autosomal dominant rare syndrome, with incomplete penetrance, characterized by the association of paragangliomas and/or pheochromocytomas and gastrointestinal stromal tumors (GISTs). CSS is caused by germline heterozygous loss-of-function pathogenic variants (PVs) in the succinate dehydrogenase subunit genes (SDHB, SDHC, SDHD), with SDHB and SDHD being the most frequent. To date, only 2 germline SDHC PVs (c.43 C > T; c.405 + 1G > A) have been described in 3 patients with CSS. Three patients with CSS and very distinct clinical presentations are reported here: 1 caused by a germline SDHC large deletion and the others with metastatic GIST and negative genetic investigation for SDHx defects. Two cases (1 and 2) presented with pheochromocytoma (case 1 also with abdominal paraganglioma) and metastatic GIST. Although these 2 cases fulfilled the diagnostic criteria for CSS, the genetic investigation for SDHx PVs by next-generation sequencing and multiplex ligation-dependent probe amplification was negative. Case 3 had a large abdominal paraganglioma and a small low-grade GIST not associated with recurrence or metastasis. This case harbored a germline SDHC exon 3 deletion, not previously reported. In conclusion, CSS is a rare and morbid disease with distinct clinical presentations and genetic heterogeneity, which can contribute to underdiagnosis.

PMID:38021081 | PMC:PMC10675988 | DOI:10.1210/jcemcr/luad139

Use of Lipid Lowering Medications in Youth

Fetched: November 29th, 2023, 5:00am GMT by Melissa L. Miller

2023 Nov 26. 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, Laferrère 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.; 2000–.

ABSTRACT

The first comprehensive pediatric dyslipidemia guidelines were published by the National Cholesterol Education Program’s Expert Panel on Blood Cholesterol Levels in Children and Adolescents in 1992 and were updated by the American Academy of Pediatrics (AAP) in 1998. In 2008 the AAP issued an updated clinical report detailing recommendations for screening and evaluation of cholesterol levels in children and adolescents as well as prevention and treatment strategies. Since the publication of the first guidelines, rates of pediatric obesity have significantly increased, resulting in a concomitant increase in dyslipidemia. Recently, options for pharmacotherapeutic interventions in pediatric patients have expanded with new FDA approved indications of several lipid lowering medications, as well as additional safety and efficacy data. In 2011, The National Heart Lung and Blood Institute (NHLBI) published its comprehensive report Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents. As with previous guidelines, lifestyle modifications with an emphasis on a heart-healthy diet and daily moderate to vigorous exercise remain an integral part of treatment for pediatric lipid disorders; however, the recommendations for patients requiring management with pharmacotherapy have changed, and will be the focus of this discussion. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:27809436 | Bookshelf:NBK395575

Permalink for 'Relationship between PIWIL1 gene polymorphisms and epithelial ovarian cancer susceptibility among southern Chinese woman: a three-center case-control study'

Relationship between PIWIL1 gene polymorphisms and epithelial ovarian cancer susceptibility among southern Chinese woman: a three-center case-control study

Fetched: November 29th, 2023, 5:00am GMT by Shanshan Liu

BMC Cancer. 2023 Nov 27;23(1):1149. doi: 10.1186/s12885-023-11651-2.

ABSTRACT

OBJECTIVE: To investigate the potential correlation between piwi-like RNA-mediated gene silencing 1 (PIWIL1) polymorphisms and susceptibility to epithelial ovarian cancer (EOC).

METHODS: A case-control study was conducted to evaluate the susceptibility of EOC using multinomial logistic regression analysis. The study analyzed the relationship between five functional single nucleotide polymorphisms (SNPs) in the PIWIL1 gene and EOC risk. Genotyping of 288 cases and 361 healthy samples from South China was identified using a TaqMan assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the relationship between the five selected SNPs and EOC susceptibility.

RESULTS: Among the five SNPs analyzed, the rs10848087 G > A and rs7957349 G > C variants significantly increased the susceptibility of EOC, rs10773771 C > T was associated with a decreased risk of EOC, while the rs35997018 and rs1106042 variants were not in Hardy-Weinberg equilibrium (p < 0.05). The rs10848087 G > A was significantly associated with increased risk of EOC in individuals with metastasis, FIGO stage I and III, low and high pathological grade, tumor numbers ≤ 3 and > 3, tumor size > 3 cm and ≤ 3 cm, pregnant more than 3 times, pre-menopausal status, and strong positive expression of ER (estrogen receptor), PR (progesterone receptor), PAX8 (paired-box 8), wild-type p53 (tumor protein 53), WT1 (Wilm's tumor gene), P16 (cyclin-dependent kinase inhibitor 2A). In addition, rs10848087 G > A enhanced the EOC risk of cases with negative/mild positive expression of wild p53 and Ki67, and with or without mutant p53 expression. The rs7957349 G > C variant was linked to an increased risk of EOC in subgroups with certain characteristics, including age equal or less than 53 years, metastasis, clinical stage I, low pathological grade, tumor number, tumor size, pregnant times, post-menopause, pre-menopause, and strong positive expression of wild p53 and Ki67 (Antigen identified by monoclonal antibody Ki-67), as well as without mutant p53 expression. The rs10773771 CT/TT alleles were identified to have a protective effect on EOC in women aged 53 years or older, as well as in cases with metastasis, advanced clinical stage, high pathological grade, multiple tumors, tumor size equal to or less than 3 cm, history of pregnancy, post-menopausal status, and strong positive expression of ER, PR, wild-type p53, PAX8, WT1, P16, and Ki67. Furthermore, rs10773771 CT/TT also showed a protective effect in patients with negative or mildly positive expression of PR, PAX8, wild-type p53, WT1, and P16, as well as positive expression of mutant p53. Compared to the reference haplotype GCG, individuals harboring haplotypes GTG were found to have a significantly decreased susceptibility to EOC. PIWIL1 was significantly expressed in the thyroid, pituitary, and adrenal glands with rs7957349 CC alleles.

CONCLUSIONS: PIWIL1 rs10848087 and rs7957349 were associated with increased risk of EOC, while rs10773771 may have a protective effect against EOC. These genetic variants may serve as potential biomarkers for EOC susceptibility in the South China population.

PMID:38012622 | PMC:PMC10680212 | DOI:10.1186/s12885-023-11651-2

Ambiguous Genitalia in the Newborn

Fetched: November 28th, 2023, 5:00am GMT by Christa E. Flück

2023 Nov 13. 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, Laferrère 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.; 2000–.

ABSTRACT

Ambiguous genitalia in a newborn are the clinical sign of atypical sexual development of the external genitalia in utero. This condition is rare and can result from various underlying factors, including certain disorders with potentially severe consequences, such as cortisol deficiency due to congenital adrenal hyperplasia. Therefore, it is crucial to promptly determine etiology when ambiguity is observed. The formation of typical male or female external genitalia is a complex process involving a cascade of genetic and physiological events that begin with sex determination and progress through the differentiation of internal and external reproductive structures. When this process is disrupted and does not occur in the typical manner, it is referred to as a difference or disorder of sex development (DSD). Not all DSD cases present with ambiguous genitalia at birth; for example, complete androgen insensitivity syndrome does not, but all cases of ambiguous genitalia are the result of a DSD. This chapter focuses on genital ambiguity associated with DSD in newborns who have either a 46,XY or 46,XX chromosomal sex. However, DSD with genital ambiguity may also be observed in newborns with other combinations of sex chromosomes, such as 45,X/46,XY. The chapter offers a comprehensive overview of the evaluation and management of newborns with ambiguous genitalia. It emphasizes the importance of a structured medical assessment of the external genitalia to diagnose and determine the underlying cause of genital ambiguity. It includes tables for differential diagnosis and step-by-step workup algorithms to guide medical professionals in their evaluation. It also includes additional information on structured physical assessments of external genitalia and tables with normative values for hormonal measurements, which are recommended in the diagnostic process. As the etiology of genital ambiguity in newborns is diverse and can have significant implications for management, the authors stress that obtaining an accurate diagnosis through a professional medical workup is crucial. The chapter highlights the recommendation for newborns with ambiguous genitalia (DSD) to be cared for by highly specialized, interdisciplinary DSD teams. These teams are equipped with medical and psychosocial expertise, and specialized psychologists are available to support parents and caregivers. The chapter recognizes that having a child with ambiguous genitalia can be very stressful for parents. It underscores the importance of early education, access to expert care through DSD network teams, psychological support, shared decision-making, and promoting acceptance and inclusivity. By providing comprehensive support and guidance, families can better navigate the challenges and uncertainties they may encounter when caring for a newborn with ambiguous genitalia. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:25905391 | Bookshelf:NBK279168

Catecholamine-induced hypertensive crises: current insights and management

Fetched: November 28th, 2023, 5:00am GMT by Matthew A Nazari

Lancet Diabetes Endocrinol. 2023 Dec;11(12):942-954. doi: 10.1016/S2213-8587(23)00256-5. Epub 2023 Nov 6.

ABSTRACT

Phaeochromocytomas and paragangliomas (PPGLs) release catecholamines leading to catecholamine-induced hypertensive (CIH) crises, with blood pressure greater than or equal to 180/120 mm Hg. CIH crises can be complicated by tachyarrhythmias, hypotension, or life-threatening target organ damage while treatment remains undefined, often requiring co-management between endocrinologists and cardiologists. Furthermore, biochemical diagnosis of a PPGL as a cause of a CIH crisis can be difficult to identify or confounded by comorbid conditions, potentially resulting in misdiagnosis. Here, we combine relevant evidence, 60 years of collective clinical experience, insights derived from assessing over 2600 patients with PPGL, and supplementary outcomes from 100 patients (treated at the National Institutes of Health) with a CIH crisis to inform diagnosis and treatment of CIH crises. Recognising that disparities exist between availability, cost, and familiarity of various agents, flexible approaches are delineated allowing for customisation, given institutional availability and provider preference. A CIH crisis and its complications are readily treatable with available drugs, with effective intervention defining an avenue for mitigating consequent morbidity and mortality in patients with PPGL.

PMID:37944546 | DOI:10.1016/S2213-8587(23)00256-5

Paragangliomas and Anemia: Literature Review and Case Report

Fetched: November 28th, 2023, 5:00am GMT by Maria-Daniela Tănăsescu

Medicina (Kaunas). 2023 Oct 30;59(11):1925. doi: 10.3390/medicina59111925.

ABSTRACT

Paragangliomas are rare neuroendocrine tumors that arise from the extra-adrenal autonomic paraganglia, i.e., small organs consisting mainly of neuroendocrine cells that are derived from the embryonic neural crest and have the ability to secrete catecholamines. Paragangliomas can derive from either parasympathetic or sympathetic paraganglia. Most of the parasympathetic ganglia-derived paragangliomas are nonfunctional, and symptoms result from mass effect. Conversely, the sympathetic paragangliomas are functional and produce catecholamine. Although such patients could have symptoms similar to pheochromocytoma, mass effect symptoms, or non-specific symptoms, being benign tumors, they can also present with anemia, specifically iron-deficiency anemia. Considering that neoplastic pathology is chronically accompanied by moderate, normochromic, normocytic anemia, association between paragangliomas that are mostly benign but with a potential degree of malignancy and anemia is not as frequent as expected, with only 12 cases reported in the literature. We report a case of a 54-year-old female patient diagnosed with a paraganglioma of the carotid glomus accompanied by severe normochromic, normocytic anemia, which reached normal limits after excision of the paraganglioma.

PMID:38003974 | PMC:PMC10673208 | DOI:10.3390/medicina59111925

Primary adrenal diffuse large B cell Lymphoma with Tumor thrombus in central adrenal vein: a case report and literature review

Fetched: November 28th, 2023, 5:00am GMT by Qingfei Xing

BMC Endocr Disord. 2023 Nov 24;23(1):258. doi: 10.1186/s12902-023-01496-y.

ABSTRACT

Primary adrenal lymphoma (PAL) is a rare disease confined wholly or chiefly to extramural involvement. Tumor thrombus in the central adrenal vein, renal vein, and inferior vena cava has been reported in adrenal pheochromocytoma, adrenocortical carcinoma, adrenal metastasis carcinoma, and adrenal leiomyosarcoma. Primary adrenal diffuse large B cell lymphoma with tumor thrombus in the central adrenal vein has rarely been reported in the current study. ( We searched in PubMed, Web of Science databases, Embase, and Medline in the English language from 1970 to December 2022. The keywords used were "Primary adrenal lymphoma " and " tumor thrombus".) CASE PRESENTATION: In this report, we discuss the case of a 57-year-old woman who complained of abdominal discomfort following cold stimulation, low back pain, anorexia, fatigue, and weight loss for 1 year. Contrast-enhanced spiral computed tomography (CT) showed mild-to-moderate enhancement of the bilateral masses and central adrenal vein tumor thrombus. After an exhaustive study, the patient was diagnosed with primary adrenal diffuse large B-cell lymphoma. In the diagnosis of PAL, the possibility of a tumor embolism in the central adrenal vein, renal vein, or inferior vena cava should be considered, although this is rare.

PMID:37996831 | PMC:PMC10668467 | DOI:10.1186/s12902-023-01496-y

Permalink for 'Influence of obesity and overweight in surgical outcomes of adrenalectomy for primary adrenal disease: A cohort study of 146 cases'

Influence of obesity and overweight in surgical outcomes of adrenalectomy for primary adrenal disease: A cohort study of 146 cases

Fetched: November 28th, 2023, 5:00am GMT by César Mínguez Ojeda

Endocrinol Diabetes Nutr (Engl Ed). 2023 Nov;70(9):564-571. doi: 10.1016/j.endien.2023.11.003.

ABSTRACT

OBJECTIVE: To evaluate the impact of obesity and overweight on surgical outcomes in a large cohort of patients who underwent adrenalectomy due to benign or malignant primary adrenal disease.

METHODS: A retrospective single-center study of patients without history of active extraadrenal malignancy, with adrenal tumors operated on consecutively in our center between January 2010 and December 2022. Obesity was defined as a body mass index (BMI)≥30kg/m² and overweight as BMI between 25.0 and 30.0kg/m².

RESULTS: Of 146 patients with adrenal tumors who underwent adrenalectomy, 9.6% (n=14) were obese, 54.8% (n=80) overweight and 35.6% (n=52) normal weight. Obese patients had higher diastolic blood pressure (87.6±12.22 vs. 79.3±10.23mmHg, P=0.010) and a higher prevalence of dyslipidemia (57.1% vs. 25.8%, P=0.014) and bilateral tumors (14.3% vs. 3.1%, P=0.044) than non-obese patients. The rates of intraoperative and of postsurgical complications were similar between obese/overweight patients and patients with normal weight. However, a significantly higher rate of postsurgical complications (27.3% vs. 5.7%, P=0.009) and a longer hospital stay (5.4±1.39 vs. 3.5±1.78 days, P=0.007) were observed in patients with obesity than in non-obese patients. In the multivariant analysis, obesity, age, ASA>2 and tumor size were independent risk factors for postoperative complications, with obesity being the most important factor (OR 23.34 [2.23-244.24]).

CONCLUSION: Obesity and overweight are common conditions in patients who undergo adrenalectomy. Adrenalectomy is considered a safe procedure in patients with overweight, but it is associated with a higher risk of postsurgical complications and longer hospital stay in obese patients.

PMID:37996201 | DOI:10.1016/j.endien.2023.11.003

Permalink for 'Inflammation-based scores in benign adrenocortical tumours are linked to the degree of cortisol excess: a retrospective single-centre study'

Inflammation-based scores in benign adrenocortical tumours are linked to the degree of cortisol excess: a retrospective single-centre study

Fetched: November 28th, 2023, 5:00am GMT by Vittoria Favero

Eur J Endocrinol. 2023 Nov 8;189(5):517-526. doi: 10.1093/ejendo/lvad151.

ABSTRACT

OBJECTIVE: Benign adrenocortical tumours are diagnosed in ∼5% of adults and are associated with cortisol excess in 30%-50% of cases. Adrenal Cushing's syndrome (CS) is rare and leads to multiple haematological alterations. However, little is known about the effects of the much more frequent mild autonomous cortisol secretion (MACS) on immune function. The aim of this study was to evaluate the haematological alterations in benign adrenocortical tumours with different degrees of cortisol excess.

DESIGN AND METHODS: We investigated 375 patients: 215 with non-functioning adrenal tumours (NFAT), 138 with MACS, and 22 with CS. We evaluated the relationship between the degree of cortisol excess and full blood count as well as multiple inflammation-based scores, including the neutrophil-to-lymphocyte ratio (NLR), the lymphocyte-to-monocyte ratio (LMR), and the systemic immune-inflammation index (SII).

RESULTS: We observed a gradual and significant increase of leucocytes, neutrophils, and monocytes across the spectrum of cortisol excess, from NFAT over MACS to CS. Neutrophil-to-lymphocyte ratio and SII were significantly higher in both MACS and CS when compared to NFAT (P < .001 and P = .002 for NLR and P = .006 and P = .021 for SII, respectively). Conversely, LMR was lower in MACS and CS than in NFAT (P = .01 and <.001, respectively) but also significantly lower in CS compared to MACS (P = .007).

CONCLUSIONS: Neutrophil-to-lymphocyte ratio, SII, and LMR correlated with the degree of cortisol excess in benign adrenocortical tumours and were altered in patients with CS and MACS. These findings suggest that, similar to clinically overt CS, MACS also affects the immune function, potentially contributing to the MACS-associated comorbidities.

PMID:37962923 | DOI:10.1093/ejendo/lvad151

Can Ashwagandha Benefit the Endocrine System?-A Review

Fetched: November 26th, 2023, 5:00am GMT by Michał Wiciński

Int J Mol Sci. 2023 Nov 20;24(22):16513. doi: 10.3390/ijms242216513.

ABSTRACT

Withania somnifera, also known as Ashwagandha, has been used in traditional medicine for thousands of years. Due to the wide range of its activities, there has been interest in its possible beneficial effects on the human body. It is proved that, among others, Ashwagandha has anti-stress, anti-inflammatory, antimicrobial, anti-cancer, anti-diabetic, anti-obesity, cardioprotective, and hypolipidemic properties. Particularly interesting are its properties reported in the field of psychiatry and neurology: in Alzheimer's disease, Parkinson's disease, multiple sclerosis, depression, bipolar disorder, insomnia, anxiety disorders and many others. The aim of this review is to find and summarize the effect that Ashwagandha root extract has on the endocrine system and hormones. The multitude of active substances and the wide hormonal problems faced by modern society sparked our interest in the topic of Ashwagandha's impact on this system. In this work, we also attempted to draw conclusions as to whether W. somnifera can help normalize the functions of the human endocrine system in the future. The search mainly included research published in the years 2010-2023. The results of the research show that Ashwagandha can have a positive effect on the functioning of the endocrine system, including improving the secretory function of the thyroid gland, normalizing adrenal activity, and multidirectional improvement on functioning of the reproductive system. The main mechanism of action in the latter appears to be based on the hypothalamus-pituitary-adrenal (HPA) axis, as a decrease in cortisol levels and an increase in hormones such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in men were found, which results in stress level reduction and improvement in fertility. In turn, other studies prove that active substances from W. somnifera, acting on the body, cause an increase in the secretion of triiodothyronine (T3) and thyroxine (T4) by the thyroid gland and a subsequent decrease in the level of thyroid-stimulating hormone (TSH) in accordance with the hypothalamus-pituitary-thyroid (HPT) axis. In light of these findings, it is clear that Ashwagandha holds significant promise as a natural remedy for various health concerns, especially those related to the endocrine system. Future research may provide new insights into its mechanisms of action and expand its applications in both traditional and modern medicine. The safety and toxicity of Ashwagandha also remain important issues, which may affect its potential use in specific patient groups.

PMID:38003702 | PMC:PMC10671406 | DOI:10.3390/ijms242216513

Permalink for 'SEL1L3 as a link molecular between renal cell carcinoma and atherosclerosis based on bioinformatics analysis and experimental verification'

SEL1L3 as a link molecular between renal cell carcinoma and atherosclerosis based on bioinformatics analysis and experimental verification

Fetched: November 23rd, 2023, 5:00am GMT by Haoyuan Wang

Aging (Albany NY). 2023 Nov 21;15. doi: 10.18632/aging.205227. Online ahead of print.

ABSTRACT

BACKGROUND: Renal cancer, the most common type of kidney cancer, develops in the renal tubular epithelium. Atherosclerosis of the aorta is the primary cause of atherosclerosis. However, the underlying mechanisms remain unclear.

METHODS: The renal clear cell carcinoma RNA sequence profile was obtained from The Cancer Genome Atlas (TCGA) database, and the atherosclerosis datasets GSE28829 and GSE43292 based on GPL570 and GPL6244 was obtained from the Gene Expression Omnibus (GEO) database. The difference and hub genes were identified by the Limma protein-protein interaction (PPI) network in R software. Functional enrichment, survival, and immunoinfiltration analyses were performed. The role of SEL1L3 in the ErbB/PI3K/mTOR signaling pathway, apoptosis, invasion, cell cycle, and inflammation was analyzed using western blotting.

RESULTS: 764 DEGs were identified from TCGA Kidney Renal Clear Cell Carcinoma (KIRC) dataset. A total of 344 and 117 DEGs were screened from the GSE14762 and GSE53757 datasets, respectively. Functional enrichment analysis results primarily indicated enrichment in the transporter complex, DNA-binding transcription activator activity, morphogenesis of the embryonic epithelium, stem cell proliferation, adrenal overactivity and so on. Fifteen common DEGs overlapped among the three datasets. The PPI network revealed that SEL1L3 was the core gene. Survival analysis showed that lower SEL1L3 expression levels led to a worse prognosis. Immune cell infiltration analysis showed that SEL1L3 expression was significantly correlated with antibody-drug conjugates (aDC), B cells, eosinophils, interstitial dendritic cells (iDC), macrophages, and more.

CONCLUSIONS: SEL1L3 plays an important role in renal clear cell carcinoma and atherosclerosis and may be a potential link between them.

PMID:37993256 | DOI:10.18632/aging.205227

Permalink for 'Isolated Adrenal Metastases of Castration-Resistant Prostate Cancer: Excellent Response to 177Lu-PSMA With No Adrenal Insufficiency'

Isolated Adrenal Metastases of Castration-Resistant Prostate Cancer: Excellent Response to 177Lu-PSMA With No Adrenal Insufficiency

Fetched: November 23rd, 2023, 5:00am GMT by Edanur Topal

Clin Nucl Med. 2023 Nov 22. doi: 10.1097/RLU.0000000000004964. Online ahead of print.

ABSTRACT

We present isolated bilateral adrenal metastases successfully treated with 177Lu-PSMA in a 66-year-old man diagnosed with castration-resistant prostate cancer. The patient had progression under chemotherapy as depicted by 68Ga-PSMA PET/CT showing intense bilateral PSMA uptake in the adrenal masses, and metastasis-directed therapies were considered as the first option for improving survival because the patient was oligometastatic. However, surgery and radiotherapy were not justifiable options due to the high risk of definitive adrenal insufficiency; therefore, the patient received 4 cycles of 177Lu-PSMA treatment. 68Ga-PSMA PET/CT showed near-complete response in bilateral adrenal metastases, and no sign of adrenal insufficiency was observed during follow-up.

PMID:37991439 | DOI:10.1097/RLU.0000000000004964

Fibromyalgia

Fetched: November 22nd, 2023, 5:00am GMT by Gregory Kaltsas

2023 Nov 9. 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, Laferrère 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.; 2000–.

ABSTRACT

Fibromyalgia is a clinical entity characterized by the combination of chronic widespread pain and other non-pain symptoms, including fatigue, poor sleep, and cognitive disturbances, which can exhibit symptom variation not only between different patients, but also in the same patient during the course of the disease. These symptoms are relatively common and non-specific. They can be encountered in other disorders that may overlap with fibromyalgia, often without having clear boundaries, while their nature makes them difficult to be objectively defined and quantified. These issues have led to significant controversy over the definition and the diagnostic criteria of fibromyalgia. It has been suggested that the markers of physical and psychological distress have a continuous distribution in the general population with fibromyalgia patients being at the extreme end of this continuum. Genetic predisposition in combination with environmental factors, are responsible for each individual’s position in this this distribution. In recent years more knowledge has been obtained to better understand the environmental factors that seem to be important in triggering fibromyalgia. Most of them act as stressors superimposed onto a deranged stress-response system leading to dys-regulation of the nociceptive system and the appearance of clinical symptoms. The aim of the therapy is to relieve pain and motivate the patients to become more physically active using a multimodal individualized therapeutic strategy that includes education, exercise, cognitive-behavioral approaches and medications. The response to current therapeutic modalities varies significantly, with some patients responding adequately, while others do not seem to experience any long-term benefit. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:25905317 | Bookshelf:NBK279092

Immune System Effects on the Endocrine System

Fetched: November 22nd, 2023, 5:00am GMT by Maria P. Yavropoulou

2023 Nov 8. 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, Laferrère 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.; 2000–.

ABSTRACT

Among the most important and complex systems in the human body are the endocrine and immune systems. Emerging research over the last decade has shed light on their remarkable interplay, revealing a multitude of bidirectional communication pathways and reciprocal regulation mechanisms. Endocrine diseases, such as autoimmune thyroiditis, diabetes mellitus type 1 and type 2, osteoporosis, and disorders of the hypothalamic-pituitary-adrenal (HPA) axis, as well as endocrine malignancies, such as thyroid cancer, are highly interconnected with dysregulations of the immune system. Thus, multiple cytokines, chemokines, and evolving inflammatory processes are involved in the pathogenesis of immune-related endocrine disorders, providing potential targets for immune-based therapeutic approaches. In this chapter, we provide a comprehensive overview of the molecular mechanisms underlying these complex endocrine-immune interactions, and discuss the implications of immune system function or dysfunction in endocrine disorders. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:25905362 | Bookshelf:NBK279139

Type 2 Diabetes in Children and Adolescents- A Focus on Diagnosis and Treatment

Fetched: November 22nd, 2023, 5:00am GMT by Orit Pinhas-Hamiel

2023 Nov 7. 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, Laferrère 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.; 2000–.

ABSTRACT

Nearly three decades have passed since the first publications on type 2 diabetes (T2D) in children and adolescents, and it is now well established as a global problem. As the prevalence of obesity continues to increase within the general population, diagnosing T2D in adolescents presents a multifaceted challenge. In this chapter, we shall delve into the epidemiological aspects, as well as the distinct characteristics inherent to various types of diabetes. Cohort studies with long-term follow-ups have illuminated our understanding of the alarming incidence of complications in adolescents diagnosed with T2D. Recent approvals of novel pharmaceutical interventions for teenagers have ushered in a new era of hope. Hopefully, in the forthcoming decade, we anticipate a decline in the prevalence of these complications. However, in the interim, a proactive and assertive approach remains essential for addressing the complications associated with T2D in adolescents. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:37983339 | Bookshelf:NBK597439

Permalink for 'Prevalence and risk factors of bone metastasis and the development of bone metastatic prognostic classification system: a pan-cancer population study'

Prevalence and risk factors of bone metastasis and the development of bone metastatic prognostic classification system: a pan-cancer population study

Fetched: November 22nd, 2023, 5:00am GMT by Zhouyang Hu

Aging (Albany NY). 2023 Nov 19;15. doi: 10.18632/aging.205224. Online ahead of print.

ABSTRACT

BACKGROUND: The prevalence of bone metastasis (BM) varies among primary cancer patients, and it has a significant impact on prognosis. However, there is a lack of research in this area. This study aims to explore the clinical characteristics, prevalence, and risk factors, and to establish a prognostic classification system for pan-cancer patients with BM.

METHODS: The data obtained from the Surveillance, Epidemiology and End Results database were investigated. The prevalence and prognosis of patients with BM were analyzed. Hierarchical clustering was used to develop a prognostic classification system.

RESULTS: From 2010 to 2019, the prevalence of BM has increased by 41.43%. BM most commonly occurs in cancers that originate in the adrenal gland, lung and bronchus and overlapping lesion of digestive systems. Negative prognostic factors included older age, male sex, poorer grade, unmarried status, low income, non-metropolitan living, advanced tumor stages, previous chemotherapy, and synchronous liver, lung, and brain metastasis. Three categories with significantly different survival time were identified in the classification system.

CONCLUSIONS: The clinical features, prevalence, risk factors, and prognostic factors in pan-cancer patients with BM were investigated. A prognostic classification system was developed to provide survival information and aid physicians in selecting personalized treatment plans for patients with BM.

PMID:37983179 | DOI:10.18632/aging.205224

Treatment of Vulvar Angiolymphoid Hyperplasia with Eosinophilia with Topical Corticosteroids

Fetched: November 22nd, 2023, 5:00am GMT by Nor Fazil Jaber

Acta Derm Venereol. 2023 Nov 20;103:adv19659. doi: 10.2340/actadv.v103.19659.

NO ABSTRACT

PMID:37982725 | PMC:PMC10680461 | DOI:10.2340/actadv.v103.19659

Unusual encephalopathy with Wernicke-Korsakoff syndrome-like features due to adjuvant nivolumab for malignant melanoma

Fetched: November 22nd, 2023, 5:00am GMT by Saniya Malik

J Oncol Pharm Pract. 2023 Nov 19:10781552231215088. doi: 10.1177/10781552231215088. Online ahead of print.

ABSTRACT

INTRODUCTION: Autoimmune encephalitis is a rare immune-related adverse event of PD-1 inhibitors, nivolumab and pembrolizumab. Autoimmune hypophysitis can also be seen with the use of these agents. The relationship between these two phenomena is currently unknown.

CASE REPORT: We describe a 79-year-old man with anterior scalp melanoma who received adjuvant nivolumab therapy. Sixteen weeks after the completion of nivolumab therapy, the patient presented to the hospital with altered mental status, anterograde amnesia, and symptoms of nausea and vomiting. The patient's encephalopathy was associated with confabulations. Workup identified increased CSF protein without increased cellularity, along with decreased serum cortisol and ACTH levels. This was consistent with encephalitis and central adrenal insufficiency.

MANAGEMENT AND OUTCOME: The patient had a robust clinical response to steroids, with resolution of mental status changes and normalization of blood pressure. He continues to receive maintenance steroid therapy without any further symptoms six months later.

CONCLUSIONS: We report herein a unique case of encephalopathy in the setting of nivolumab use for the treatment of melanoma. The condition resembled Korsakoff psychosis seen in the setting of alcoholism and was associated with central adrenal insufficiency. A prompt response to steroids was both diagnostic and therapeutic in our case, suggesting the resolution of autoimmune phenomena related to nivolumab.

PMID:37981786 | DOI:10.1177/10781552231215088

Survival following complete resection of neuroblastoma in novel orthotopic rat xenograft model

Fetched: November 20th, 2023, 5:00am GMT by ReidAnn E Sever

Sci Rep. 2023 Nov 18;13(1):20214. doi: 10.1038/s41598-023-47537-3.

ABSTRACT

Neuroblastoma accounts for 15% of pediatric cancer deaths, despite multimodal therapy including surgical resection. Current neuroblastoma rodent models are insufficient for studying the impact of surgery and combination treatments, largely due to the small size of mouse models. Human neuroblastoma SK-N-BE(2) cells were injected into the left adrenal gland of 5-6-week-old RNU homozygous nude rats. Rats were either monitored by MRI until humane endpoint was reached or after 5 weeks underwent operative tumor resection, followed by monitoring for recurrence and survival. Following neuroblastoma cell implantation, the majority of tumors grew to greater than 5000 mm³ within 5.5-6.5 weeks, meeting the humane endpoint. Surgical resection was successfully done in 8 out of 9 rats, extending survival following tumor implantation from a median of 42 days to 78 days (p < 0.005). Pathology was consistent with human neuroblastoma, showing small round blue cell tumors with Homer-Wright rosettes, high mitoses and karyorrhectic index, and strong PHOX2B staining. Thus, we have established a novel orthotopic xenograft rat model of neuroblastoma and demonstrated increased survival of rats after surgical tumor resection. This model can be used for the development of surgical techniques, such as the use of intraoperative molecular imaging or assessment of combination therapies that include surgery.

PMID:37980388 | PMC:PMC10657433 | DOI:10.1038/s41598-023-47537-3

Permalink for 'Epidemiological and clinical characteristics of children with peripheral neuroblastic tumors: a study on a Moroccan population'

Epidemiological and clinical characteristics of children with peripheral neuroblastic tumors: a study on a Moroccan population

Fetched: November 19th, 2023, 5:00am GMT by Aroua Anissi Eddaibouni

J Cancer Res Clin Oncol. 2023 Nov 18. doi: 10.1007/s00432-023-05502-7. Online ahead of print.

ABSTRACT

PURPOSE: Peripheral neuroblastic tumors are the most common extracranial cancers found in children, and they are characterized by a diverse spectrum of clinical manifestations and heterogeneous behaviors. This study aimed to investigate the epidemiological and clinical characteristics of children with peripheral neuroblastic tumors admitted to the Department of Pediatric Hematology and Oncology of the Hospital August 20 in Casablanca.

METHODS: The medical files of 48 children with peripheral neuroblastic tumors addressed to our department between February 2018 and February 2023 were reviewed. The clinical and demographic characteristics of patients were analyzed by the Statistical Package for the Social Sciences (SPSS), survival curves were obtained by Kaplan-Meier technique, and we assigned the tumor stage to patients based on the International Neuroblastoma Risk Group Staging System (INRGSS).

RESULTS: The median age of diagnosis was 30 months (1-174), with a ratio F/M of 1.28. 93.75% of patients had neuroblastoma, and the rest had ganglioneuroma. About 64.6% of patients had at their initial presentations stage M of peripheral neuroblastic tumors. The adrenal region made up 71% of the primary tumor site. The bone was one of the most prevalent metastatic sites (54.2%). The five-year overall survival rate was 35.4%.

CONCLUSION: Overall, this study revealed a high stage of peripheral neuroblastic tumors in the majority of the diagnosed patients in our Department of Pediatric Hematology and Oncology. Moreover, the heterogeneity of peripheral neuroblastic tumors makes clinical recognition difficult and, in general, too late.

PMID:37979055 | DOI:10.1007/s00432-023-05502-7

False-Positive Metastatic Disease Due to Bilateral Ectopic Adrenal Tissue

Fetched: November 18th, 2023, 5:00am GMT by Edward Li

Clin Nucl Med. 2023 Nov 17. doi: 10.1097/RLU.0000000000004944. Online ahead of print.

ABSTRACT

A 60-year-old man was referred for staging of prostate cancer. Initial CT scan demonstrated soft tissue lesions in bilateral renal hila, which demonstrated mild 68Ga-PSMA avidity and moderate FDG avidity on sequential PET scans suspicious for malignancy. Biopsy confirmed adrenal cortical tissue. This case highlights an exceedingly rare occurrence of ectopic adrenocortical tissue in both renal hila.

PMID:37976522 | DOI:10.1097/RLU.0000000000004944

Multiple endocrine neoplasia type 2: towards a risk-based approach integrating molecular and biomarker results

Fetched: November 18th, 2023, 5:00am GMT by Andreas Machens

Curr Opin Oncol. 2023 Nov 6. doi: 10.1097/CCO.0000000000001009. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: Significant advances have transformed our understanding of the molecular biology and natural history of multiple endocrine neoplasia type 2 (MEN2). This progress enacted a paradigm shift with regard to routine neck dissection for medullary thyroid cancer and total adrenalectomy for pheochromoytoma. The purpose of this review is to summarize key molecular and clinical data underpinning the current risk-based approach to MEN2 that integrates molecular and biomarker results.

RECENT FINDINGS: Early identification and biochemical monitoring of rearranged during transfection (RET) carriers yield important lead time. Within these 'windows of opportunity', total thyroidectomy alone, avoiding incremental morbidity from node dissection; 'tissue-sparing' subtotal adrenalectomy, balancing risks of steroid dependency with pheochromocytoma recurrence in adrenal remnants; and parathyroidectomy of enlarged glands only, weighing risks of postoperative hypoparathyroidism against hyperactive parathyroid glands left behind, are adequate therapies.

SUMMARY: All that is needed to determine a RET carriers' risk of medullary thyroid cancer, pheochromocytoma and/or primary hyperparathyroidism in the molecular era is patient age, underlying RET mutation, and biomarker levels. As broader testing begins to penetrate healthcare, the needle on population genomic screening and education needs to be moved forward to complete the transition from symptom-based to preventive healthcare.

PMID:37975407 | DOI:10.1097/CCO.0000000000001009

Hemokinin-1 is a mediator of chronic restraint stress-induced pain

Fetched: November 18th, 2023, 5:00am GMT by Éva Borbély

Sci Rep. 2023 Nov 16;13(1):20030. doi: 10.1038/s41598-023-46402-7.

ABSTRACT

The Tac4 gene-derived hemokinin-1 (HK-1) binds to the NK1 receptor, similarly to Substance P, and plays a role in acute stress reactions and pain transmission in mice. Here we investigated Tac4 mRNA expression in stress and pain-related regions and its involvement in chronic restraint stress-evoked behavioral changes and pain using Tac4 gene-deleted (Tac4^-/-) mice compared to C57Bl/6 wildtypes (WT). Tac4 mRNA was detected by in situ hybridization RNAscope technique. Touch sensitivity was assessed by esthesiometry, cold tolerance by paw withdrawal latency from 0°C water. Anxiety was evaluated in the light-dark box (LDB) and open field test (OFT), depression-like behavior in the tail suspension test (TST). Adrenal and thymus weights were measured at the end of the experiment. We found abundant Tac4 expression in the hypothalamic-pituitary-adrenal axis, but Tac4 mRNA was also detected in the hippocampus, amygdala, somatosensory and piriform cortices in mice, and in the frontal regions and the amygdala in humans. In Tac4^-/- mice of both sexes, stress-induced mechanical, but not cold hyperalgesia was significantly decreased compared to WTs. Stress-induced behavioral alterations were mild or absent in male WT animals, while significant changes of these parameters could be detected in females. Thymus weight decrease can be observed in both sexes. Higher baseline anxiety and depression-like behaviors were detected in male but not in female HK-1-deficient mice, highlighting the importance of investigating both sexes in preclinical studies. We provided the first evidence for the potent nociceptive and stress regulating effects of HK-1 in chronic restraint stress paradigm. Identification of its targets might open new perspectives for therapy of stress-induced pain.

PMID:37973885 | PMC:PMC10654722 | DOI:10.1038/s41598-023-46402-7

Corticotropin-producing pheochromocytoma in multiple endocrine neoplasia type 1

Fetched: November 18th, 2023, 5:00am GMT by D V Rebrova

Probl Endokrinol (Mosk). 2023 Nov 11;69(5):55-64. doi: 10.14341/probl13260.

ABSTRACT

A clinical case of a man 66 y.o. who was diagnosed with hormone-inactive pituitary macroadenoma complicated by corneal erosion and partial atrophy of the optic nerve of the left eye due to exophthalmos. The increase in prolactin level was regarded due to a «stalk-effect». The patient underwent a transnasal pituitary adenomectomy with subsequent regression of symptoms. After 4 years, against the background of a new coronavirus infection, increasing general weakness, headaches, a crisis increase in blood pressure and tachycardia attacks appeared. Computed tomography (CT) accidentally revealed an adrenal incidentaloma, in laboratory tests - hypercortisolism, elevated ACTH levels, hypokalemia, hyperglycemia, increased levels of metanephrine and normetanephrine. The patient developed acute steroid psychosis, after which an adrenalectomy with a tumor was performed, a pheochromocytoma was histologically confirmed. After surgery, there was a regression of symptoms, the development of adrenal insufficiency with reduced levels of ACTH and cortisol. Upon further examination, a polynodose euthyroid goiter was established, the biopsy of the nodes - Hashimoto's thyroiditis (Bethesda II). Meanwhile, primary hyperparathyroidism was detected. According to ultrasound, scintigraphy with Ts99m-Technetril and CT revealed an increase of left parathyroid gland. A bilateral revision of the neck, removal of the right upper and left upper parathyroid adenomas were performed. In the postoperative period, the levels of calcium and parathyroid hormone were normalized. Given the presence of a combination of multiple tumors of the endocrine system (primary hyperparathyroidism, corticotropin-producing pheochromocytoma, hormone-inactive pituitary macroadenoma, polynodose euthyroid goiter), the MEN1 syndrome was clinically established. The study of 2 and 10 exons of the MEN1 gene revealed no mutations, which does not exclude the presence of a hereditary syndrome. The patient continues observation. In the available literature in Russian and English languages the case of ACTH pheochromocytoma as part of the MEN type 1 syndrome have not been found. Therefore, we consider the presented case to be the first one.

PMID:37968952 | PMC:PMC10680545 | DOI:10.14341/probl13260

Surgical treatment of pheochromocytoma

Fetched: November 18th, 2023, 5:00am GMT by Sh Sh Shikhmagomedov

Probl Endokrinol (Mosk). 2023 Nov 11;69(5):39-44. doi: 10.14341/probl13283.

ABSTRACT

This review article contains a summary of modern aspects of preoperative preparation, surgical treatment, and follow-up of patients with adrenal pheochromocytomas. The main component of preoperative preparation is the use of alpha-blockers. The need to prescribe them to all patients is increasingly disputed, especially for patients without severe hypertension. An increasing number of publications demonstrate positive results of treatment without the use of alpha-blockers, advocating an individual approach and the use of the drug according to certain indications. Minimally invasive endoscopic techniques of adrenalectomy have become widespread in surgical treatment. They are represented by laparoscopic and retroperitonescopic technic, including using their single-port modifications. The earliest possible intersection of the central vein in the past was considered the most important aspect of adrenalectomy for pheochromocytoma, currently, due to the development of surgical techniques and anesthesiological manuals, this has ceased to be a mandatory rule of successful surgery. Despite the significant influence of the intersection of this vessel on intraoperative hemodynamics, surgical tactics with its later intersection have their own justifications and do not lead to a deterioration in treatment results. The standard volume of surgical intervention for pheochromocytomas is total adrenalectomy, however, in the presence of hereditary syndromes, such as multiple endocrine neoplasia type 2 syndrome, neurofibomatosis type 1, von Hippel-Lindau syndrome, it is possible to perform cortical-sparing adrenalectomy.

PMID:37968950 | PMC:PMC10680547 | DOI:10.14341/probl13283

Melatonin, BAG-1 and cortisol circadian interactions in tumor pathogenesis and patterned immune responses

Fetched: November 17th, 2023, 5:00am GMT by George Anderson

Explor Target Antitumor Ther. 2023;4(5):962-993. doi: 10.37349/etat.2023.00176. Epub 2023 Oct 25.

ABSTRACT

A dysregulated circadian rhythm is significantly associated with cancer risk, as is aging. Both aging and circadian dysregulation show suppressed pineal melatonin, which is indicated in many studies to be linked to cancer risk and progression. Another independently investigated aspect of the circadian rhythm is the cortisol awakening response (CAR), which is linked to stress-associated hypothalamus-pituitary-adrenal (HPA) axis activation. CAR and HPA axis activity are primarily mediated via activation of the glucocorticoid receptor (GR), which drives patterned gene expression via binding to the promotors of glucocorticoid response element (GRE)-expressing genes. Recent data shows that the GR can be prevented from nuclear translocation by the B cell lymphoma-2 (Bcl-2)-associated athanogene 1 (BAG-1), which translocates the GR to mitochondria, where it can have diverse effects. Melatonin also suppresses GR nuclear translocation by maintaining the GR in a complex with heat shock protein 90 (Hsp90). Melatonin, directly and/or epigenetically, can upregulate BAG-1, suggesting that the dramatic 10-fold decrease in pineal melatonin from adolescence to the ninth decade of life will attenuate the capacity of night-time melatonin to modulate the effects of the early morning CAR. The interactions of pineal melatonin/BAG-1/Hsp90 with the CAR are proposed to underpin how aging and circadian dysregulation are associated with cancer risk. This may be mediated via differential effects of melatonin/BAG-1/Hsp90/GR in different cells of microenvironments across the body, from which tumors emerge. This provides a model of cancer pathogenesis that better integrates previously disparate bodies of data, including how immune cells are regulated by cancer cells in the tumor microenvironment, at least partly via the cancer cell regulation of the tryptophan-melatonin pathway. This has a number of future research and treatment implications.

PMID:37970210 | PMC:PMC10645470 | DOI:10.37349/etat.2023.00176

Analysis of IGFBP7 expression characteristics in pan-cancer and its clinical relevance to stomach adenocarcinoma

Fetched: November 17th, 2023, 5:00am GMT by Hui-Wen Xu

Transl Cancer Res. 2023 Oct 31;12(10):2596-2612. doi: 10.21037/tcr-23-1055. Epub 2023 Oct 24.

ABSTRACT

BACKGROUND: Insulin-like growth factor (IGF) binding proteins (IGFBPs) are involved in tumorigenesis and cancer progression. IGFBP7 has been shown to act as either a tumor suppressive gene or an oncogene in many tumors, including stomach adenocarcinoma (STAD). To provide a more systematic and comprehensive understanding of IGFBP7 gene, we performed an integrative pan-cancer analysis and explored further with the case of STAD.

METHODS: We compared the expression data of IGFBP7 in various cancer and normal tissues obtained from The Cancer Genome Atlas (TCGA) database and the Genotype-Tissue Expression (GTEx) database. The TISIDB web portal was used to analyze the associations of IGFBP7 with cancer molecular subtypes and immune subtypes. We also analyzed the predictive ability and prognostic values of IGFBP7 in pan-cancer, as well as explored its targeted binding proteins and their biological functions. Additionally, we examined the relationship between IGFBP7 and the clinical characteristics of STAD, investigated the co-expression genes and biological functions of differentially expressed genes (DEGs), and validated the mRNA and protein expression levels of IGFBP7 using gastric cancer (GC) and adjacent normal tissues in a small self-case-control study.

RESULTS: IGFBP7 was found to be overexpressed in STAD and downregulated in many other cancers. The mRNA and protein expression levels of IGFBP7 were also significantly higher in the collected GC tissues compared with adjacent tissues. Expression of IGFBP7 varied significantly across molecular subtypes of nine different cancer types and immune subtypes of eight types, with the highest expression observed in the genomically stable molecular subtype and C3 inflammatory immune subtype in STAD. IGFBP7 demonstrated an area under the curve (AUC) >0.7 for predicting 16 cancer types, and an AUC >0.9 for seven types. Patients in the higher IGFBP7 expression group showed a poorer prognosis for adrenal cortical carcinoma (ACC) and low-grade glioma (LGG), while demonstrating a more favorable prognosis for kidney renal clear cell carcinoma (KIRC). IGFBP7 expression in STAD was significantly associated with T stage, pathological stage, histologic grade, and Helicobacter pylori infection.

CONCLUSIONS: IGFBP7 showed promise as a biomarker for prediction and prognosis in pan-cancer. IGFBP7 was found to be overexpressed in STAD, and its expression was closely associated with the clinical characteristics of STAD.

PMID:37969374 | PMC:PMC10643967 | DOI:10.21037/tcr-23-1055

Efficacy and feasibility of catheter-based adrenal ablation on Cushing's syndrome associated hypertension

Fetched: November 17th, 2023, 5:00am GMT by Z C Yan

Zhonghua Xin Xue Guan Bing Za Zhi. 2023 Nov 24;51(11):1152-1159. doi: 10.3760/cma.j.cn112148-20230801-00045.

ABSTRACT

Objective: To explore the value of catheter-based adrenal ablation in treating Cushing's syndrome (CS)-associated hypertension. Methods: A clinical study was conducted in patients with CS, who received catheter-based adrenal ablation between March 2018 and July 2023 in Daping Hospital. Parameters monitored were blood pressure (outpatient and 24-hour ambulatory), body weight, clinical characteristics, serum cortisol and adrenocorticotropic hormone (ACTH) at 8 am, 24-hour urinary free cortisol (24 h UFC), fasting blood glucose and postoperative complications. Procedure effectiveness was defined as blood pressure returning to normal levels (systolic blood pressure<140 mmHg (1 mmHg=0.133 kPa) and diastolic blood pressure<90 mmHg), cortisol and 24 h UFC returning to normal and improvement of clinical characteristics. The parameters were monitored during follow up in the outpatient department at 1, 3, 6, and 12 months after catheter-based adrenal ablation. Results: A total of 12 patients (aged (40.0±13.2) years) were reviewed. There were 5 males, with 5 cases of adenoma and 7 with hyperplasia from imaging studies. Catheter-based adrenal ablation was successful in all without interruption or surgical conversion. No postoperative complication including bleeding, puncture site infection, adrenal artery rupture or adrenal bleeding was observed. The mean follow up was 28 months. Compared to baseline values, body weight declined to (59.48±11.65) kg from (64.81±10.75) kg (P=0.008), fasting blood glucose declined to (4.54±0.83) mmol from (5.53±0.99) mmol (P=0.044), outpatient systolic blood pressure declined to (128±21) mmHg from (140±19) mmHg (P=0.005), diastolic blood pressure declined to (78±10) mmHg from (86±11) mmHg (P=0.041), and the mean ambulatory daytime diastolic blood pressure declined to (79±12) mmHg from (89±8) mmHg (P=0.034). Catheter-based adrenal ablation in 8 patients was defined as effective with their 24 h UFC significantly reduced after the procedure (1 338.41±448.06) mmol/L from (633.66±315.94) mmol/L, P=0.011). The change of 24 h UFC between the effective treatment group and ineffective group was statistically significant (P=0.020). The postoperative systolic blood pressure in the treated adenoma group was significantly lower than those of hyperplasia group (112±13) mmHg vs. (139±20) mmHg, P=0.026). Conclusions: For patients with CS-associated hypertension who are unwilling or unable to undergo surgical treatment, catheter-based adrenal ablation could improve the blood pressure and cortisol level. Catheter-based adrenal ablation could be a safe, effective, and minimally invasive therapy. However, our results still need to be validated in further large-scale studies.

PMID:37963750 | DOI:10.3760/cma.j.cn112148-20230801-00045

Permalink for 'Risk and incidence of endocrine immune related adverse effects under checkpoint inhibitor mono or combination therapy in solid tumors: a meta-analysis of randomized controlled trials'

Risk and incidence of endocrine immune related adverse effects under checkpoint inhibitor mono or combination therapy in solid tumors: a meta-analysis of randomized controlled trials

Fetched: November 16th, 2023, 5:00am GMT by Irfan Vardarli

J Clin Endocrinol Metab. 2023 Nov 15:dgad670. doi: 10.1210/clinem/dgad670. Online ahead of print.

ABSTRACT

CONTEXT: Few meta-analyses regarding the incidence of endocrine immune related adverse effects (eirAEs) have been published and many trials were published thereafter.

OBJECTIVE: To assess the risk and incidence of eirAEs of any grade and grade 3-5 by immune checkpoint inhibitor (ICI) mono or combination-therapy in solid tumors current literature was updated in this comprehensive meta-analysis.

METHODS: An electronic search using PubMed/Medline, Embase and the Cochrane Library was performed. Randomized controlled studies (RCT) assessing eirAEs under ICI-mono or ICI-combination therapy were selected. Stata software version 17 was used for statistical analyses and risk of bias was evaluated by using Review Manager version 5.3.

RESULTS: 69 RCTs with 80 independent reports, involving 42,886 patients were included in the study. Meta-analysis revealed the following pooled estimates for the risk ratio and the incidence, respectively: for any grade hypothyroidism 7.81 (95% CI, 5.68-10.74, p< 0.0001) and 7.64% (95% CI, 6.23-9.17, p< 0.0001); significantly increased also for hyperthyroidism, hypophysitis/hypopituitarism and adrenal insufficiency; and for insulin-dependent diabetes mellitus 1.52 (95% CI, 1.07-2.18, p= 0.02), and 0.087% (95% CI, 0.019-0.189, p= 0.0006), respectively. Meta-regression showed that combination of ICIs (nivolumab plus ipilimumab and durvalumab plus tremelimumab, respectively) is an independent risk factor for any grade hypophysitis/hypopituitarism, and that ICI agent is an independent factor of risk for adrenal insufficiency, but that cancer type is not an independent risk factor for eirAEs.

CONCLUSION: We showed that risk, independent from cancer type, and incidence of eAEs are substantially increased under ICI therapy. Combination of ICIs is increasing the risk for eirAEs, in particular for hypophysitis/hypopituitarism.

PMID:37967245 | DOI:10.1210/clinem/dgad670

Permalink for 'Intratumoral androgen biosynthesis associated with 3β-hydroxysteroid dehydrogenase 1 promotes resistance to radiotherapy in prostate cancer'

Intratumoral androgen biosynthesis associated with 3β-hydroxysteroid dehydrogenase 1 promotes resistance to radiotherapy in prostate cancer

Fetched: November 16th, 2023, 5:00am GMT by Shinjini Ganguly

J Clin Invest. 2023 Nov 15;133(22):e165718. doi: 10.1172/JCI165718.

ABSTRACT

Half of all men with advanced prostate cancer (PCa) inherit at least 1 copy of an adrenal-permissive HSD3B1 (1245C) allele, which increases levels of 3β-hydroxysteroid dehydrogenase 1 (3βHSD1) and promotes intracellular androgen biosynthesis. Germline inheritance of the adrenally permissive allele confers worse outcomes in men with advanced PCa. We investigated whether HSD3B1 (1245C) drives resistance to combined androgen deprivation and radiotherapy. Adrenally permissive 3βHSD1 enhanced resistance to radiotherapy in PCa cell lines and xenograft models engineered to mimic the human adrenal/gonadal axis during androgen deprivation. The allele-specific effects on radiosensitivity were dependent on availability of DHEA, the substrate for 3βHSD1. In lines expressing the HSD3B1 (1245C) allele, enhanced expression of DNA damage response (DDR) genes and more rapid DNA double-strand break (DSB) resolution were observed. A correlation between androgen receptor (AR) expression and increased DDR gene expression was confirmed in 680 radical prostatectomy specimens. Treatment with the nonsteroidal antiandrogen enzalutamide reversed the resistant phenotype of HSD3B1 (1245C) PCa in vitro and in vivo. In conclusion, 3βHSD1 promotes prostate cancer resistance to combined androgen deprivation and radiotherapy by upregulating DNA DSB repair. This work supports prospective validation of early combined androgen blockade for high-risk men harboring the HSD3B1 (1245C) allele.

PMID:37966114 | PMC:PMC10645386 | DOI:10.1172/JCI165718

Permalink for 'Transoesophageal bronchoscopic ultrasound-guided fine-needle aspiration (EUS-B-FNA) for left adrenal gland (LAG) sampling: A report of three cases with a review of the literature'

Transoesophageal bronchoscopic ultrasound-guided fine-needle aspiration (EUS-B-FNA) for left adrenal gland (LAG) sampling: A report of three cases with a review of the literature

Fetched: November 15th, 2023, 5:00am GMT by Rohit Vadala

Lung India. 2023 Nov-Dec;40(6):550-554. doi: 10.4103/lungindia.lungindia_381_22.

ABSTRACT

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a standard-of-care modality for evaluating mediastinal lymph nodes and masses. The EBUS bronchoscope may also be introduced through the oesophageal route to perform sampling of accessible lesions, a technique described as transoesophageal bronchoscopic ultrasound-guided fine-needle aspiration (EUS-B-FNA). Because of the central oesophageal approach, EUS-B-FNA provides easy access to the left para-tracheal, subcarinal and para-oesophageal lymph nodes. In addition, the left adrenal gland (LAG) can also be imaged and sampled during the EUS-B-FNA procedure. In patients with suspected lung cancer, accurate staging is essential. Adrenal metastasis is relatively common and may often be a solitary metastatic site. We describe three cases where EUS-B-FNA was performed to safely sample the enlarged LAG in suspected lung cancer. We also review the literature on the performance characteristics of EUS-B-FNA for LAG aspiration.

PMID:37961966 | DOI:10.4103/lungindia.lungindia_381_22

Prognosis of Adrenal Oncocytic Neoplasms (AONs): Literature Review of 287 Cases and Presentation of the Oldest Patient

Fetched: November 15th, 2023, 5:00am GMT by Enrico Coppola Bottazzi

J Clin Med. 2023 Nov 4;12(21):6925. doi: 10.3390/jcm12216925.

ABSTRACT

INTRODUCTION: The adrenocortical oncocytic neoplasms (AONs) are rare tumors of the adrenal gland, classified as oncocytoma (AO), oncocytic neoplasm of uncertain malignant potential (AONUMP) and oncocytic carcinoma (AOC). The aim of this study was to perform a review of the literature, in order to evaluate the prognosis of these rare cancers. We also reported the oldest patient with AON.

METHODS: A comprehensive literature review using as key words "adrenal oncocytoma", "adrenal oncocytic neoplasm", and "adrenal oncocytic carcinoma" was performed.

REPORT OF THE CASE: We report the case of an 88-year-old woman receiving a left open adrenalectomy for an AON (15 × 10 × 8 cm). The considerable size and weight together with the presence of necrosis were indicative for a lesion with an uncertain potential for malignancy, according to Weiss modified criteria. After two years, the patient was free from any sign of recurrence.

RESULTS: Only 287 AONs were detected in the scientific literature, exploring OVID, MEDLINE, PubMed and SCOPUS as dataset. These tumors are usually incidentalomas with an unpredictable malignant potential. Surgical resection remains the mainstay of treatment for AON.

CONCLUSION: AO and AONUMP have an excellent prognosis and a low mortality rate, with only three cases of recurrence reported in the literature and one metastatic case four years after first adrenal surgery. In contrast, AOC carries a high risk of local relapses, distant metastasis, and a significantly higher mortality rate (30%). Surgical resection remains the primary treatment for adrenal oncocytic neoplasms.

PMID:37959390 | PMC:PMC10649738 | DOI:10.3390/jcm12216925

Permalink for 'Incidence of Endocrine-Related Dysfunction in Patients Treated with New Immune Checkpoint Inhibitors: A Meta-Analysis and Comprehensive Review'

Incidence of Endocrine-Related Dysfunction in Patients Treated with New Immune Checkpoint Inhibitors: A Meta-Analysis and Comprehensive Review

Fetched: November 14th, 2023, 5:00am GMT by Won Sang Yoo

Endocrinol Metab (Seoul). 2023 Nov 13. doi: 10.3803/EnM.2023.1785. Online ahead of print.

ABSTRACT

BACKGROUND: This study investigated the incidence of endocrine immune-related adverse events (irAEs) for recently developed immune checkpoint inhibitor (ICI) drugs.

METHODS: We collected studies on newly developed ICI drugs using PubMed/Medline, Embase, and Cochrane Library from inception through January 31, 2023. Among ICI drugs, nivolumab, pembrolizumab, and ipilimumab were excluded from the new ICI drugs because many papers on endocrine-related side effects have already been published.

RESULTS: A total of 44,595 patients from 177 studies were included in this analysis. The incidence of hypothyroidism was 10.1% (95% confidence interval [CI], 8.9% to 11.4%), thyrotoxicosis was 4.6% (95% CI, 3.8% to 5.7%), hypophysitis was 0.8% (95% CI, 0.5% to 1.1%), adrenal insufficiency was 0.9% (95% CI, 0.7% to 1.1%), and hyperglycemia was 2.3% (95% CI, 1.6% to 3.4%). Hypothyroidism and thyrotoxicosis occurred most frequently with programmed cell death protein-1 (PD-1) inhibitors (13.7% and 7.5%, respectively). The rate of endocrine side effects for the combination of a programmed death-ligand 1 inhibitor (durvalumab) and cytotoxic T lymphocyte-associated antigen 4 inhibitor (tremelimumab) was higher than that of monotherapy. In a meta-analysis, the combination of tremelimumab and durvalumab had a 9- to 10-fold higher risk of pituitary and adrenal-related side effects than durvalumab alone.

CONCLUSION: Newly developed PD-1 inhibitors had a high incidence of thyroid-related irAEs, and combined treatment with durvalumab and tremelimumab increased the risk of pituitary- and adrenal-related irAEs. Based on these facts, it is necessary to predict the endocrine side effects corresponding to each ICI drug, diagnose and treat them appropriately, and try to reduce the morbidity and mortality of patients.

PMID:37956967 | DOI:10.3803/EnM.2023.1785

Personalized treatment of pheochromocytoma

Fetched: November 14th, 2023, 5:00am GMT by Nicolas Schlegel

Chirurgie (Heidelb). 2023 Nov 13. doi: 10.1007/s00104-023-01988-6. Online ahead of print.

ABSTRACT

BACKGROUND: Pheochromocytoma is a rare but severe disease of the adrenal glands. The aim of this study is to present and discuss recent developments in the diagnosis and treatment of pheochromocytoma.

MATERIAL AND METHODS: A narrative review article based on the most recent literature is presented.

RESULTS AND DISCUSSION: The proportion of pheochromocytomas as tumors of adrenal origin is about 5% of incidentally discovered adrenal tumors. The classical symptomatic triad of headaches, sweating, and palpitations occurs in only about 20% of patients, while almost all patients show at least 1 of these symptoms. To diagnose pheochromocytoma, levels of free plasma metanephrines or alternatively, fractionated metanephrines in a 24‑h urine collection is required in a first step. In the second step an imaging procedure, computed tomography (CT) or magnetic resonance imaging (MRI), is performed to localize the adrenal tumor. Functional imaging is also recommended to preoperatively detect potential metastases. Genetic testing should always be offered during the course of treatment as 30-40% of pheochromocytomas are associated with genetic mutations. The dogma of preoperative alpha blockade is increasingly being questioned and has been controversially discussed in recent years. Minimally invasive removal of the adrenal tumor is the standard surgical procedure to cure patients with pheochromocytoma. The transabdominal and retroperitoneal laparoscopic approaches are considered equivalent. The choice of the minimally invasive procedure depends on the expertise and experience of the surgeon and should be tailored accordingly. Individualized and regular follow-up care is important after surgery.

PMID:37957403 | DOI:10.1007/s00104-023-01988-6

Thyroid and Adrenal Dysfunction in Hemoglobinopathies Before and After Allogeneic Hematopoietic Cell Transplant

Fetched: November 14th, 2023, 5:00am GMT by Mamatha Mandava

J Endocr Soc. 2023 Oct 31;7(12):bvad134. doi: 10.1210/jendso/bvad134. eCollection 2023 Nov 2.

ABSTRACT

PURPOSE: To determine the rate and clinical characteristics associated with abnormal thyroid and adrenal function in recipients of nonmyeloablative hematopoietic cell transplantation (HCT) for sickle cell disease (SCD) and beta-thalassemia.

METHODS: We retrospectively reviewed patients who enrolled in 4 nonmyeloablative HCT regimens with alemtuzumab and total body irradiation (TBI). Baseline and annual post-HCT data were compared, which included age, sex, sickle phenotype, thyroid panel (total T3, free T4, thyroid stimulating hormone, antithyroid antibodies), cortisol level, ACTH stimulation testing, ferritin, medications, and other relevant medical history.

RESULTS: Among 43 patients in haploidentical transplant and 84 patients in the matched related donor protocols with mostly SCD, the rate of any thyroid disorder pre-HCT was 3.1% (all subclinical hypothyroidism) and post-HCT was 29% (10 hypothyroidism, 4 Grave's disease, and 22 subclinical hypothyroidism). Ninety-two (72%) patients had ferritin >1000 ng/dL, of which 33 patients (35.8%) had thyroid dysfunction. Iron overload was noted in 6 of 10 patients with hypothyroidism and 12 of 22 patients with subclinical hypothyroidism.Sixty-one percent were on narcotics for pain control. With respect to adrenal insufficiency (AI) pre-HCT, 2 patients were maintained on corticosteroids for underlying rheumatologic disorder and 8 had AI diagnosed during pre-HCT ACTH stimulation testing (total 10, 7.9%). Post-HCT, an additional 4 (3%) developed AI from corticosteroid use for acute graft vs host disease, Evans syndrome, or hemolytic anemia.

CONCLUSION: Although iron overload was common in SCD, thyroid dysfunction pre-HCT related to excess iron was less common. Exposure to alemtuzumab or TBI increased the rates of thyroid dysfunction post-HCT. In contrast, AI was more common pre-HCT, but no risk factor was identified. AI post-HCT was infrequent and associated with corticosteroid use for HCT-related complications.

PMID:37953902 | PMC:PMC10635581 | DOI:10.1210/jendso/bvad134

In Situ Spatial Reconstruction of Distinct Normal and Pathological Cell Populations Within the Human Adrenal Gland

Fetched: November 14th, 2023, 5:00am GMT by Rui Fu

J Endocr Soc. 2023 Oct 25;7(12):bvad131. doi: 10.1210/jendso/bvad131. eCollection 2023 Nov 2.

ABSTRACT

The human adrenal gland consists of concentrically organized, functionally distinct regions responsible for hormone production. Dysregulation of adrenocortical cell differentiation alters the proportion and organization of the functional zones of the adrenal cortex leading to disease. Current models of adrenocortical cell differentiation are based on mouse studies, but there are known organizational and functional differences between human and mouse adrenal glands. This study aimed to investigate the centripetal differentiation model in the human adrenal cortex and characterize aldosterone-producing micronodules (APMs) to better understand adrenal diseases such as primary aldosteronism. We applied spatially resolved in situ transcriptomics to human adrenal tissue sections from 2 individuals and identified distinct cell populations and their positional relationships. The results supported the centripetal differentiation model in humans, with cells progressing from the outer capsule to the zona glomerulosa, zona fasciculata, and zona reticularis. Additionally, we characterized 2 APMs in a 72-year-old woman. Comparison with earlier APM transcriptomes indicated a subset of core genes, but also heterogeneity between APMs. The findings contribute to our understanding of normal and pathological cellular differentiation in the human adrenal cortex.

PMID:37953901 | PMC:PMC10638100 | DOI:10.1210/jendso/bvad131

Total adrenalectomy versus subtotal adrenalectomy for bilateral pheochromocytoma: meta-analysis

Fetched: November 14th, 2023, 5:00am GMT by Donatella Schiavone

BJS Open. 2023 Nov 1;7(6):zrad109. doi: 10.1093/bjsopen/zrad109.

ABSTRACT

BACKGROUND: Bilateral pheochromocytomas are rare and often heritable. Total adrenalectomy leads to a definitive oncological cure, with subsequent definitive hypocortisolism. Subtotal adrenalectomy is a possible alternative. The aim of this study was to assess the effects of total adrenalectomy and subtotal adrenalectomy on bilateral pheochromocytoma in terms of post-surgical rate of recurrence, metastatic disease, and steroid dependence.

METHODS: Systematic searches in the bibliographic databases PubMed, Embase, and Europe PMC were performed for 1945 to 1 June 2023. PRISMA guidelines were followed and the PICO strategy was applied to English-language studies comparing subtotal adrenalectomy with total adrenalectomy. A random-effects model was used to assess the different outcomes for studies with high heterogeneity. The Newcastle-Ottawa scale and the Risk Of Bias In Non-randomized Studies of Interventions ('ROBINS-I') tool were used to assess quality and risk of bias.

RESULTS: From a total of 12 909 studies, 1202 patients (from 10 retrospective studies) were eligible for the meta-analysis. In six studies, including 1176 patients, the recurrence rate after subtotal adrenalectomy and total adrenalectomy was 14.1 versus 2.6 per cent respectively (OR 4.91, 95 per cent c.i. 1.30 to 18.54; P = 0.020; I2 72 per cent). In nine studies, including 1124 patients, the rate of post-surgical steroid dependence was 93.3 versus 11.6 per cent after total adrenalectomy and subtotal adrenalectomy respectively (OR 0.003, 95 per cent c.i. 0.0003 to 0.03; P < 0.00001; I2 66 per cent). Based on two studies, including 719 patients, no differences were evident regarding the occurrence of post-surgery metastatic disease.

CONCLUSION: Subtotal adrenalectomy leads to less post-surgical primary adrenal insufficiency, but leads to a higher postoperative recurrence rate. Future prospective randomized studies, with clear eligibility criteria, are needed to confirm these results.

PMID:37945270 | PMC:PMC10635800 | DOI:10.1093/bjsopen/zrad109

Pituitary gland volumes and stress: Results of a population-based adult sample

Fetched: November 12th, 2023, 5:00am GMT by Johanna Klinger-König

J Psychiatr Res. 2023 Dec;168:325-333. doi: 10.1016/j.jpsychires.2023.10.047. Epub 2023 Oct 28.

ABSTRACT

Early and chronic stress was reported to alter the hypothalamic-pituitary-adrenal axis functioning which regulates the secretion of cortisol. Nevertheless, few studies mainly focused on specific study populations (e.g. adolescents, pregnant women, and psychiatric patients), and researched interactive associations of pituitary volumes and single stress markers. The present study used pituitary volumes of two adult general-population cohorts of the Study of Health in Pomerania (SHIP-START-2: N = 1026, 54% Men, 30-90 years; SHIP-TREND-0: N = 1868, 53% Men, 21-82 years). In linear regression models, main effects of the pituitary volumes as well as interaction effects with childhood abuse and neglect (Childhood Trauma Questionnaire) were estimated using depressive symptoms (Beck Depression Inventory-II), and serum cortisol concentrations as outcome variables. The results of both cohorts were integrated via meta-analyses. No main effect between pituitary volumes and depressive symptoms was observed (START-2: β = -0.004 [-0.082; 0.075], p = .929; TREND-0: β = 0.020 [-0.033; 0.073], p = .466; Meta-analysis: β = 0.012 [-0.031; 0.056], p = .580). However, larger pituitary volumes were associated with more depressive symptoms in participants with more severe childhood neglect (START-2: β = 0.051 [-0.024; 0.126], p = .183; TREND-0: β = 0.083 [0.006; 0.159], p = .034; Meta-analysis: β = 0.066 [0.013; 0.120], p = .015). Further, larger pituitary volumes were associated with lower serum cortisol concentrations in participants with more severe depressive symptoms (START-2: β = -0.087 [-0.145; -0.030], p = .003; TREND-0: β = -0.053 [-0.091; -0.015], p = .006; Meta-analysis: β = -0.063 [-0.095; -0.032], p = 8.39e-05). Summarizing, larger pituitary volumes were associated with more severe psychopathological symptoms, particularly in participants reporting early life stress. This was supported by stronger associations between pituitary volumes and cortisol concentrations in participants with more severe depressive symptoms. Future studies are needed to transfer these results into developmental stages of high hormonal changes and patient samples.

PMID:37950977 | DOI:10.1016/j.jpsychires.2023.10.047

A combined encoder-transformer-decoder network for volumetric segmentation of adrenal tumors

Fetched: November 11th, 2023, 5:00am GMT by Liping Wang

Biomed Eng Online. 2023 Nov 8;22(1):106. doi: 10.1186/s12938-023-01160-5.

ABSTRACT

BACKGROUND: The morphology of the adrenal tumor and the clinical statistics of the adrenal tumor area are two crucial diagnostic and differential diagnostic features, indicating precise tumor segmentation is essential. Therefore, we build a CT image segmentation method based on an encoder-decoder structure combined with a Transformer for volumetric segmentation of adrenal tumors.

METHODS: This study included a total of 182 patients with adrenal metastases, and an adrenal tumor volumetric segmentation method combining encoder-decoder structure and Transformer was constructed. The Dice Score coefficient (DSC), Hausdorff distance, Intersection over union (IOU), Average surface distance (ASD) and Mean average error (MAE) were calculated to evaluate the performance of the segmentation method.

RESULTS: Analyses were made among our proposed method and other CNN-based and transformer-based methods. The results showed excellent segmentation performance, with a mean DSC of 0.858, a mean Hausdorff distance of 10.996, a mean IOU of 0.814, a mean MAE of 0.0005, and a mean ASD of 0.509. The boxplot of all test samples' segmentation performance implies that the proposed method has the lowest skewness and the highest average prediction performance.

CONCLUSIONS: Our proposed method can directly generate 3D lesion maps and showed excellent segmentation performance. The comparison of segmentation metrics and visualization results showed that our proposed method performed very well in the segmentation.

PMID:37940921 | PMC:PMC10631161 | DOI:10.1186/s12938-023-01160-5

The effect of hormonal secretion on survival in adrenocortical carcinoma: A multi-center study

Fetched: November 10th, 2023, 5:00am GMT by Alaa Sada

Surgery. 2023 Nov 8:S0039-6060(23)00679-7. doi: 10.1016/j.surg.2023.04.070. Online ahead of print.

ABSTRACT

BACKGROUND: Current evidence suggests that cortisol secreting adrenocortical carcinoma has worse prognosis compared to non-secreting adrenocortical carcinoma. However, the effect of other secretory subtypes is unknown.

METHODS: This multicenter study within the American-Australian-Asian Adrenal Alliance included adults with adrenocortical carcinoma (1997-2020). We compared overall survival and disease-free survival among cortisol secreting, mixed cortisol/androgen secreting, androgen secreting, and non-secreting adrenocortical carcinoma.

RESULTS: Of the 807 patients (mean age 50), 719 included in the secretory subtype analysis: 24.5% were cortisol secreting, 13% androgen secreting, 28% mixed cortisol/androgen, 32.5% non-secreting, and 2% were mineralocorticoid secreting. Median overall survival and disease-free survival for the entire cohort were 60 and 9 months, respectively. Median overall survival was 36 months for cortisol, 30 for mixed, 60 for androgen secreting, and 115 for non-secreting adrenocortical carcinoma, P < .01. Median disease-free survival was 7 months for cortisol, 8 for mixed, 10 for androgen, and 12 for non-secreting adrenocortical carcinoma, P = .06. On multivariable analysis of age, sex, Ki67%, secretory subtype, stage, resection, and adjuvant therapy, predictors of worse overall survival were older age, higher Ki67%, stage IV, mixed secreting, R1, and no adjuvant therapy, P < .05. On subgroup analysis of R0 resection, predictors of worse overall survival included older age and higher Ki67%. Ki67% ≥40, stage III and cortisol secretion were associated with worse disease-free survival.

CONCLUSION: Mixed cortisol/androgen secreting adrenocortical carcinoma was associated with worse overall survival, while cortisol or androgen secreting alone were not. Notably, among patients after R0 resection, secretory subtype did not affect overall survival. Cortisol secreting adrenocortical carcinoma demonstrated worse disease-free survival. Ki67% remained a strong predictor of worse overall survival and disease-free survival independent of stage.

PMID:37945477 | DOI:10.1016/j.surg.2023.04.070

18 F-PSMA-1007 PET/CT in a Case of Von Hippel-Lindau Syndrome

Fetched: November 9th, 2023, 5:00am GMT by Aisheng Dong

Clin Nucl Med. 2023 Dec 1;48(12):e600-e602. doi: 10.1097/RLU.0000000000004890. Epub 2023 Oct 11.

ABSTRACT

We describe 18 F-PSMA-1007 PET/CT findings in case of von Hippel-Lindau syndrome with a cerebellar hemangioblastoma, 6 renal cell carcinomas in the bilateral kidneys, cystic lesions in the pancreas and left adrenal gland, and solid lesions in the bilateral epididymides. 18 F-PSMA-1007 PET/CT showed intense activity with SUV max of 111.3 of the cerebellar hemangioblastoma, variable activity with SUV max range of 6.4-37.6 of the renal cell carcinomas, and increased activity of the bilateral epididymal lesions (SUV max of 5.1 and 8.2 for the left and right epididymal lesions, respectively).

PMID:37844561 | DOI:10.1097/RLU.0000000000004890

Diabetes in People Living with HIV

Fetched: November 9th, 2023, 5:00am GMT by Sudipa Sarkar

2023 Nov 1. 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, Laferrère 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.; 2000–.

ABSTRACT

People living with HIV (PLWH) are living longer and also have unique risk factors for developing several metabolic diseases, including diabetes. This has been observed in both high income and low to middle income countries. Risk factors for diabetes in PLWH consist of specific antiretroviral therapies (ART), including older generation protease inhibitors and nucleoside reverse transcriptase inhibitors, lipodystrophy, and hepatitis C co-infection. In addition, obese and overweight states are common in PLWH, and an increased risk of incident diabetes has been noted with weight gain after ART initiation in PLWH, compared to individuals without HIV. Inflammation associated with HIV has also been linked to incident diabetes. This chapter reviews points to consider in the diagnosis and monitoring of diabetes in PLWH and discusses interactions that may occur between specific ART agents and glucose-lowering medications. Moreover, PLWH have risk factors for complications involving organ systems that are also affected by microvascular disease in diabetes. Because PLWH have a greater risk for cardiovascular disease (CVD) than individuals without HIV, modifiable risk factors of CVD should be addressed in the care of PLWH, considering that dyslipidemia, hypertension, and cigarette smoking are all highly prevalent in PLWH. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:31479220 | Bookshelf:NBK545886

Adrenal Gland Solitary Fibrous Tumor

Fetched: November 8th, 2023, 5:00am GMT by Rumeal D Whaley

Mayo Clin Proc. 2023 Nov;98(11):1735-1736. doi: 10.1016/j.mayocp.2023.08.008.

NO ABSTRACT

PMID:37923534 | DOI:10.1016/j.mayocp.2023.08.008

Permalink for 'Retroperitoneal yolk sac tumour encroaching the liver and adrenal gland with tumour thrombus in cavo-atrial region and hepatic veins'

Retroperitoneal yolk sac tumour encroaching the liver and adrenal gland with tumour thrombus in cavo-atrial region and hepatic veins

Fetched: November 8th, 2023, 5:00am GMT by Pujana Kanneganti

BMJ Case Rep. 2023 Nov 3;16(11):e255968. doi: 10.1136/bcr-2023-255968.

ABSTRACT

Paediatric germ cell tumours (GCT) are rare tumours and are unique because of varied clinical presentation and locations. Yolk sac tumour is the predominant malignant histology and a serum marker; alpha fetoprotein is used to see treatment response and recurrent disease. It is extremely rare to find a retroperitoneal GCT with tumour thrombus extending up to the cavo-atrial region with involvement of the hepatic veins. We report a case of retroperitoneal yolk sac tumour (RPYST) with extension to the liver and right adrenal gland along with tumour thrombus in the inferior vena cava and in the right and middle hepatic veins. The child was operated after satisfactory response to chemotherapy. Excision of the tumour along with the right adrenal gland and around 5 cm of retro-hepatic caval resection was done. Inferior vena cava resection was tolerated without reconstruction. Currently child is disease-free and symptom-free at 22 months of follow-up with normal serum marker.

PMID:37923340 | PMC:PMC10626902 | DOI:10.1136/bcr-2023-255968

SYNCHRONOUS T-LYMPHOBLASTIC LYMPHOMA AND NEUROBLASTOMA IN A 3-YEAR-OLD WITH NOVEL GERMLINE SMARCA4 AND EZH2 VARIANTS

Fetched: November 7th, 2023, 5:00am GMT by Pauline Tibout

Cold Spring Harb Mol Case Stud. 2023 Nov 6:mcs.a006286. doi: 10.1101/mcs.a006286. Online ahead of print.

ABSTRACT

T-lymphoblastic lymphoma is the most common lymphoblastic lymphoma in children, and often presents with a mediastinal mass. Lymphomatous suprarenal masses are possible but rare. Here we discuss the case of a previously healthy 3-year-old male who presented with mediastinal T-lymphoblastic lymphoma (T-LLy) with bilateral suprarenal masses. Following initial treatment, surgical biopsy of persisting adrenal masses revealed bilateral neuroblastoma (NBL). A clinical genetics panel for germline cancer predisposition did not identify any pathogenic variants. Combination large panel (864 genes) profiling analysis in the context of a precision oncology study revealed two novel likely pathogenic heterozygous variants: SMARCA4, c.1420-1G>T, p.? and EZH2 c.1943G>C p.(Ile631Phefs*44). Somatic analysis revealed potential second hits/somatic variants in EZH2 (in the T-LLy) and a segmental loss in chromosome 19p encompassing SMARCA4 (in the NBL). Synchronous cancers, especially at a young age warrant genetic evaluation for cancer predisposition; enrollment in a precision oncology program assessing germline and tumour DNA can fulfill that purpose, particularly when standard first line genetic testing is negative and in the setting of tumors that are not classic for common cancer predisposition syndromes.

PMID:37932047 | DOI:10.1101/mcs.a006286

Biological mechanisms of cancer-related fatigue in breast cancer survivors after treatment: a scoping review

Fetched: November 7th, 2023, 5:00am GMT by David García-González

J Cancer Surviv. 2023 Nov 6. doi: 10.1007/s11764-023-01477-z. Online ahead of print.

ABSTRACT

PURPOSE: Cancer-related fatigue (CRF) is the most common symptom experienced by cancer survivors. It is a multidimensional symptom affecting physical, emotional, and/or cognitive spheres, different from other types of fatigue. Characteristically is not alleviated by sleep or rest. CRF could have specific features in breast cancer survivors (BCS), because of sex, hormones, and distinct treatments. On the other hand, more than 25% of BCS report persistent CRF for 10 years or more after the diagnosis. The present study aims to recapitulate the knowledge about the biological mechanisms that potentially drive CRF in BCS after treatment.

METHODS: To answer a broad question, a scoping review methodology was used. Data were collated from three bibliographic databases: PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL). Studies were selected if they had included more than 20 BCS, after finishing their treatment, fatigue was measured with a quantitative scale and biomarkers were analyzed.

RESULTS: The final database was composed of 1896 records. Sixty-four studies finally met the eligibility criteria. Inflammation (61%), hypothalamic-pituitary-adrenal (HPA) axis dysregulation (14%), autonomic nervous system (ANS) dysfunction (11%), and diet (9%) were the biological pathways most frequently studied. Unfortunately, results from studies about inflammation and HPA axis show many inconsistencies.

CONCLUSION: More research about the role of ANS dysfunction and diet on the pathogenesis of CRF would be warranted according to the results of the review. There are some fields such as endocannabinoid systems, mitochondrial dysfunction, gut microbiota, and oxidative stress that have been insufficiently explored.

IMPLICATIONS FOR CANCER SURVIVORS: To widen the scope of future research in the physiopathology of CRF, it is necessary to identify mechanisms that would be potentially involved and have been insufficiently explored. Because of the high prevalence of CRF in BCS and the tremendous impact that fatigue has in their quality of life, it is essential to improve the efficacy of the treatments through a good knowledge of the biological basis of CRF.

PMID:37930591 | DOI:10.1007/s11764-023-01477-z

Expression of G protein-coupled receptor GPR19 in normal and neoplastic human tissues

Fetched: November 7th, 2023, 5:00am GMT by Lorena Gerlach

Sci Rep. 2023 Nov 3;13(1):18993. doi: 10.1038/s41598-023-46395-3.

ABSTRACT

Little is known about the expression of the orphan G protein-coupled receptor GPR19 at the protein level. Therefore, we developed a rabbit antibody, targeting human GPR19. After verification of the antibody specificity using GPR19-expressing cell lines and a GPR19-specific siRNA, the antibody was used for immunohistochemical staining of a variety of formalin-fixed, paraffin-embedded normal and neoplastic human tissue samples. In normal tissues, GPR19 expression was detected in a distinct cell population within the cortex, in single cells of the pancreatic islets, in intestinal ganglia, gastric chief cells, and in endocrine cells of the bronchial tract, the gastrointestinal tract, and the prostate. Among the 30 different tumour entities investigated, strong GPR19 expression was found in adenocarcinomas, typical and atypical carcinoids of the lung, and small cell lung cancer. To a lesser extent, the receptor was also present in large cell neuroendocrine carcinomas of the lung, medullary thyroid carcinomas, parathyroid adenomas, pheochromocytomas, and a subpopulation of pancreatic neuroendocrine neoplasms. In lung tumours, a negative correlation with the expression of the proliferation marker Ki-67 and a positive interrelationship with patient survival was observed. Overall, our results indicate that in adenocarcinomas and neuroendocrine tumours of the lung GPR19 may serve as a suitable diagnostic or therapeutic target.

PMID:37923782 | PMC:PMC10624815 | DOI:10.1038/s41598-023-46395-3

N-doped carbon Co/CoOx with laccase-like activity for detection of epinephrine

Fetched: November 7th, 2023, 5:00am GMT by Junlun Zhu

Mikrochim Acta. 2023 Nov 3;190(11):459. doi: 10.1007/s00604-023-06041-1.

ABSTRACT

N-doped carbon Co/CoOx with laccase-like activity was directionally designed by pyrolyzing Co-coordination polymer and applied to detect epinephrine, which revealed a new preparation strategy for laccase mimics. The formation mechanism of the N-doped carbon Co/CoOx nanozyme was reconnoitered by a thermogravimetric-mass spectrometry system (TG-MS). N-doped carbon Co/CoOx exhibited outstanding laccase-like activity, and the Michaelis-Menten constant and maximum initial velocity were calculated to be 0.087 mM and 0.0089 μM s^-1, respectively. Based on this principle, a simple colorimetric sensing platform was developed for the quantitative detection of epinephrine, which can be used to diagnose pheochromocytoma. In addition, the visual platform for detecting epinephrine exhibited a linear range of 3 to 20 μg mL^-1 and a calculated detection limit of 0.42 μg mL^-1. Therefore, the proposed colorimetric sensing platform is a promising candidate to be applied in precise early pheochromocytoma diagnosis.

PMID:37921998 | DOI:10.1007/s00604-023-06041-1

Permalink for 'Preoperative predictors for recurrence sites associated with poor post-recurrence survival after surgery of non-small cell lung cancer: a multicenter study'

Preoperative predictors for recurrence sites associated with poor post-recurrence survival after surgery of non-small cell lung cancer: a multicenter study

Fetched: November 6th, 2023, 5:00am GMT by Tetsuya Isaka

BMC Cancer. 2023 Nov 6;23(1):1064. doi: 10.1186/s12885-023-11582-y.

ABSTRACT

BACKGROUND: The recurrence site that influences post-recurrence survival (PRS) in patients with non-small cell lung cancer (NSCLC) undergoing surgery and the preoperative predictors of recurrence remain unclear.

METHODS: Cohorts 1 and 2 had 4520 (who underwent complete resection for p-stage 0-IIIA NSCLC) and 727 (who experienced recurrence after surgery) patients, respectively. The initial sites of recurrence were the lungs (309 cases), thoracic lymph nodes (225 cases), pleura (112 cases), bone (110 cases), central nervous system (86 cases), adrenal gland (25 cases), abdomen (60 cases), cervical and axillary lymph nodes (38 cases), chest wall (13 cases), skin (5 cases), and eye and tongue (3 cases). For cohort 2 analysis, the initial recurrence site that resulted in poor PRS was analyzed by multivariable analysis using a Cox proportional hazard model. For cohort 1 analysis, the preoperative predictors of recurrence patterns with poor PRS were analyzed by multivariable analysis using a logistic regression model.

RESULTS: In cohort 2 analysis, recurrence in the central nervous system (hazard ratio [HR], 1.70; p < 0.001), bone (HR, 1.75; p < 0.001), abdomen (HR, 2.39; p < 0.001), and pleura (HR, 1.69; p < 0.001) were independent poor prognostic recurrent sites for PRS and they were high-risk sites (HRS). Intrathoracic lymph nodes, cervical and axillary lymph nodes, lungs, chest wall, adrenal gland, eye and tongue, and skin were low-risk sites (LRS) that did not affect PRS. Patients with multiple LRS without HRS recurrence had a worse prognosis than those with a single LRS without HRS recurrence (5-year PRS 20.2% vs. 37.7%, p < 0.001) and were comparable to those with HRS recurrence (p = 1.000). In cohort 1 analysis, preoperative predictors for HRS and multiple LRS recurrences were positron emission tomography (PET) maximum standardized uptake value (maxSUV) ≥ 3.2 (HR, 5.09; p < 0.001), clinical nodal metastasis (HR, 2.00; p < 0.001), tumor size ≥ 2.4 cm (HR, 1.96; p < 0.001) and carcinoembryonic antigen (CEA) ≥ 5 ng/ml (HR, 1.41; p = 0.004). The cumulative incidence rates of HRS and multiple LRS recurrences within 5 years were 55.9%, 40.9%, 26.3%, 11.1%, and 3.5% (p < 0.001) in patients with 4, 3, 2, 1 and 0 of the above risks, respectively.

CONCLUSIONS: HRS and multiple LRS were vital recurrences associated with poor PRS. Preoperative PET maxSUV, clinical nodal metastasis, tumor size, and CEA level predicted the incidence of vital recurrence.

PMID:37926846 | PMC:PMC10626659 | DOI:10.1186/s12885-023-11582-y

Are nonfunctioning adrenal incidentalomas really nonfunctioning? A retrospective single-center study

Fetched: November 4th, 2023, 5:00am GMT by E Güneş

Eur Rev Med Pharmacol Sci. 2023 Oct;27(20):9895-9901. doi: 10.26355/eurrev_202310_34167.

ABSTRACT

OBJECTIVE: In patients with adrenal incidentaloma (AI), cortisol levels <1.8 μg/dL after a dexamethasone suppression test (DST) are considered nonfunctioning in terms of autonomic cortisol hypersecretion (ACH). We aimed to investigate the frequency of hypertension (HT) in patients with nonfunctioning AI.

PATIENTS AND METHODS: Individuals with AI who were admitted to the endocrinology clinic between September 2020 and May 2023 were included as the patient group, and age- and gender-matched individuals admitted with thyroid nodules between the same dates were included as the control group.

RESULTS: The participants included 123 AI patients who fulfilled the study criteria and 114 age- and sex-matched patients with thyroid nodules (age: 53.0±10.9 years and 52.9±7.4 years, respectively, p=0.98; female/male distribution: 90/33 and 91/23, respectively, p=0.28). The frequency of HT was higher in the AI group than in the control group (50.4% and 31.6%, respectively, p=0.004). The frequency of HT was significantly lower in patients with a DST result <0.87 μg/dL compared to those with a DST result ≥0.87 μg/dL (42.6% and 66.1%, respectively, p=0.009). The factors affecting HT were analyzed using binary logistic regression analysis; it was found that age [β=0.068, odds ratio (OR); 1.07 (95% confidence interval (CI); 1.02-1.12), p=0.004] and DST [β=1.18, OR; 3.24 (95% CI); 1.02-10.34, p=0.047] were independent factors.

CONCLUSIONS: The frequency of HT increases in patients with nonfunctioning AI. The reason for this increase may possibly be the presence of ACH, which is not detected by the cut-off values we currently use to exclude ACH.

PMID:37916357 | DOI:10.26355/eurrev_202310_34167

Clinical predictors and significance of adherent periadrenal fat in laparoscopic adrenalectomy

Fetched: November 4th, 2023, 5:00am GMT by Erkan Olcucuoglu

BMC Urol. 2023 Nov 1;23(1):176. doi: 10.1186/s12894-023-01348-w.

ABSTRACT

BACKGROUND: Adrenalectomy requires the anatomic preparation of the adrenal gland in the fat-rich retroperitoneal space. In the literature, it was shown that the retroperitoneal fat area affects surgical outcomes in laparoscopic adrenalectomy (LA). Besides the quantity of retroperitoneal fat, its qualitative properties play hypothetically a significant role in the safety profile and perioperative parameters of LA. In this study, we aimed to evaluate the factors associated with adherent periadrenal fat.

METHODS: The prospectively obtained demographic, preoperative, intraoperative, and postoperative data of 44 patients who underwent laparoscopic adrenalectomy in our clinic were analyzed retrospectively. The patients were divided into two groups as adherent periadrenal fat (APAF) and non-APAF group. Periadrenal fat tissue was defined as adherent or non-adherent by the attending surgeon according to the difficulty in dissection of the adrenal gland from the surrounding fat tissue during the operation.

RESULTS: The rate of female gender and presence of diabetes mellitus (DM) was higher in the APAF group (respectively, p = 0.038 and p = 0.001). A ROC curve analysis showed that the cut-off point was - 97 HU for APAF. On multivariable analysis using a stepwise regression model, we identified the presence of DM (OR = 5.073; 95% Cl = 2.192-12.387; p = 0.006) and ARFD > -97 HU (OR = 3.727; 95% Cl = 1.898-11.454; p = 0.008) as an independent predictor of APAF.

CONCLUSION: APAF seems to affect the perioperative outcomes of LA in terms of operation duration but not perioperative complications.

PMID:37915035 | PMC:PMC10621091 | DOI:10.1186/s12894-023-01348-w

Outcomes and Prognostic Analysis of Surgical Resection for Oligometastasis from Hepatocellular Carcinoma

Fetched: November 3rd, 2023, 5:00am GMT by K O Oshita

Anticancer Res. 2023 Nov;43(11):5189-5196. doi: 10.21873/anticanres.16720.

ABSTRACT

BACKGROUND/AIM: This study aimed to evaluate the outcomes of patients who underwent resection for oligometastasis from hepatocellular carcinoma (HCC) and identify the prognostic factors associated with poor survival.

PATIENTS AND METHODS: Patients who underwent resection for oligometastasis from HCC between January 2000 and April 2021 were retrospectively investigated. Oligometastasis was defined as 1-5 single organ metastases that were detected preoperatively in this study. Clinical characteristics and treatment outcomes were analyzed, and independent risk factors for poor prognosis were identified using cox proportional hazards model.

RESULTS: A total of 33 patients were included in this study. Eleven oligometastases were located in the intraabdominal lymph node, 8 in the adrenal gland, 5 in the lung, 4 in the peritoneum, 3 in the pleura, and 1 each in the supraclavicular lymph node and abdominal wall. No re-operation or operative death occurred in this study. The median OS was 44.6 months (range=5.1-150.6 months), and the median survival after primary HCC diagnosis was 116.5 months (range=7.1-253.6 months). The median cumulative incidence of recurrent HCC was 7.2 months (range=0.3-94.7 months). The multivariate analysis showed that an alpha-fetoprotein level ≥20 ng/ml and multiple primary HCC tumors were independent poor prognostic factors.

CONCLUSION: Clinical characteristics and treatment outcomes of patients who underwent resection for oligometastasis from HCC were demonstrated. A high alpha-fetoprotein level and multiple primary HCC tumors were independent poor prognostic factors. Surgical resection can be one of the treatment options for oligometastasis from HCC.

PMID:37909959 | DOI:10.21873/anticanres.16720

Clinical and genetic analysis of a case of Gitelman syndrome with comorbid Graves disease and adrenocortical adenoma

Fetched: November 3rd, 2023, 5:00am GMT by Yan Qiao

Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2023 Nov 10;40(11):1409-1413. doi: 10.3760/cma.j.cn511374-20210922-00767.

ABSTRACT

OBJECTIVE: To report the clinical and genetic characteristics of a rare case of Gitelman syndrome with comorbid Graves disease and ACTH-independent adrenocortical adenoma.

METHODS: A patient who had presented at the Nanchong Central Hospital on December 21, 2020 was selected as the study subject. Clinical data of the patient was collected. Whole-exome sequencing was carried out on DNA extracted from peripheral venous blood samples from the patient and her family members.

RESULTS: The patient, a 45-year-old woman, was found to have Graves disease, ACTH-independent Cushing syndrome, hypokalemia and hypomagnesemia following the discovery of an adrenal incidentaloma. MRI scan had revealed a 3.8 cm × 3.2 cm mass in the left adrenal gland. The mass was removed by surgery and confirmed as adrenocortical adenoma. DNA sequencing revealed that the patient and her sister have both harbored compound heterozygous variants of the SLC12A3 gene, namely c.1444-10(IVS11)G>A and c.179(exon1)C>T (p.T60M), which were respectively inherited from their father and mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.1444-10(IVS11)G>A and c.179(exon1)C>T (p.T60M) were respectively classified as a variant of uncertain significance (PM2_Supporting+PP3) and a likely pathogenic variant (PM3_Strong+PM1+PP3).

CONCLUSION: The conjunction of Gitelman syndrome with Graves disease and adrenal cortex adenoma is rather rare. The newly discovered c.1444-10(IVS11)G>A variant of the SLC12A3 gene, together with the heterozygous variant of c.179(exon1)C>T (p.T60M), probably underlay the pathogenesis in this patient.

PMID:37906151 | DOI:10.3760/cma.j.cn511374-20210922-00767

Application effects of 3D visualization reconstruction technique in pheochromocytoma/ paraganglioma surgery

Fetched: November 3rd, 2023, 5:00am GMT by Z J Zhang

Zhonghua Yi Xue Za Zhi. 2023 Oct 17;103(38):3047-3050. doi: 10.3760/cma.j.cn112137-20230703-01128.

ABSTRACT

To investigate the value of 3D visualization reconstruction technology in pheochromocytoma/paraganglioma surgery.The clinical data of 87 patients with pheochromocytoma/paraganglioma admitted to the Department of Urology of Peking Union Medical College Hospital between January 2019 and December 2022 were retrospectively analyzed, and 3D visualization model reconstruction was performed preoperatively in 47 patients [Group A:males was 24 cases,the age M(Q1, Q3)42.00(30.00, 54.00)]. while the remaining 40 patients [Group B: males was 23 cases,the age M(Q1, Q3) 44.00(30.25, 53.75)] was not. The maximum tumor diameter, operation time, intraoperative bleeding, drain retention time and postoperative hospital stay were compared between the two groups. Surgery was successfully completed in both groups. 37 (78.7%) patients in group A underwent laparoscopic surgery, 7 (14.9%) patients underwent open surgery, and 3 (6.4%) patients underwent laparoscopic-to-open surgery. Thirty-one (77.5%) patients in group B underwent laparoscopic surgery, 5 (12.5%) patients underwent open surgery, and 4 (10.0%) patients underwent laparoscopic to open surgery. There was a difference in the maximum diameter of the tumor between the two groups [(6.09±3.02) cm vs (5.32±1.76) cm, P<0.05], the retention time of the drainage tube was significantly shorter in group A compared with group B [(3.20±1.38) d vs (4.02±1.98) d, P<0.05], and the length of the hospital stay after surgery was significantly shorter [(5.75±2.12) d vs (6.49±3.37) d, P<0.05]. Comparison of operation time and intraoperative bleeding between the two groups showed no statistically significant difference (P>0.05).Two cases of postoperative anemia and one case of pulmonary atelectasis in group B patients improved before discharge. Conclusion when the tumor diameter is>6 cm or has a close relationship with the surrounding organs and blood vessels, the use of 3D visual reconstruction technology can formulate and implement a more accurate and safe surgical plan, shorten the retention time of the drainage tube and postoperative hospitalization time, which is conducive to the patient's postoperative recovery and reduce postoperative complications.

PMID:37813656 | DOI:10.3760/cma.j.cn112137-20230703-01128

Role of Glucose and Lipids in the Atherosclerotic Cardiovascular Disease in Patients with Diabetes

Fetched: November 2nd, 2023, 5:00am GMT by Kenneth R. Feingold

2023 Oct 29. 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, Laferrère 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.; 2000–.

ABSTRACT

Atherosclerotic cardiovascular disease (ASCVD) is a major cause of morbidity and mortality in both men and women with T1DM and T2DM. In patients with T1DM, intensive glycemic control results in a reduction in ASCVD. However, intensive glycemic control does not have a major impact in reducing ASCVD in patients with T2DM. Metformin, pioglitazone, SGLT2 inhibitors, and certain GLP-1 receptor agonists have been shown to decrease major cardiovascular events in patients with T2DM to a greater extent than other treatment modalities. In patients with T2DM other risk factors including, hypertension and dyslipidemia, play a major role in inducing ASCVD and control of these risk factors is paramount. In patients with T1DM in good glycemic control, the lipid profile is very similar to the general population. In contrast, in patients with T2DM, even with good glycemic control, there are frequently lipid abnormalities (elevated TG and non-HDL-C, decreased HDL-C, and an increase in small dense LDL). In both T1DM and T2DM, poor glycemic control increases TG levels and decreases HDL-C levels with modest effects on LDL-C levels. Extensive studies have demonstrated that statins decrease ASCVD in patients with diabetes. Treatment with high doses of potent statins reduces ASCVD events to a greater extent than low dose statin therapy. Adding fibrates or niacin to statin therapy has not been shown to further decrease ASCVD events. In contrast, studies have shown that the combination of a statin and ezetimibe or a statin and a PCSK9 inhibitor result in a greater decrease in ASCVD events than statins alone. Studies have suggested that EPA, an omega-3-fatty acid, when added to statins also reduces ASCVD events but this result is controversial. In statin intolerant patients with T2DM bempedoic acid decreases ASCVD events. Current recommendations state that most patients with diabetes should be on statin therapy. In certain patients with diabetes ezetimibe, PCSK9 inhibitors, and bempedoic acid can play a role in reducing ASCVD. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:25905182 | Bookshelf:NBK278947

Idiopathic Short Stature and Growth Failure of Unknown Etiology

Fetched: November 2nd, 2023, 5:00am GMT by Mabel Yau

2023 Oct 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, Laferrère 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.; 2000–.

ABSTRACT

Idiopathic short stature (ISS) is defined by a height standard deviation score (SDS) ≤ -2.25 (≤1.2nd percentile) in pediatric patients for whom diagnostic evaluation has excluded other causes of short stature, and growth hormone levels are above 10 nanograms per milliliter in response to physiologic/pharmacologic stimulation. This definition, while comprehensive, is static and does not consider the importance of longitudinal follow up of growth, and consideration of evolving causes of growth hormone deficiency in these children. Using three illustrative cases, we highlight the importance of longitudinal evaluation of children with short stature to establish a growth pattern, identifying evolving causes of GH deficiency which may not be apparent on the initial work up, as well as exclusion of non-growth hormone related factors that affect growth including malabsorptive diseases, familial short stature, constitutional delay in puberty, Turner's syndrome, and SHOX Gene haploinsufficiency to accurately make a diagnosis of growth failure of unknown etiology (GFUE). For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:37910635 | Bookshelf:NBK596800

Dual Aldosterone- and Cortisol-Secreting Adrenal Cortical Carcinoma: Pre- and Perioperative Evaluation and Management

Fetched: November 2nd, 2023, 5:00am GMT by Rebecca Rosenberg

JCEM Case Rep. 2023 Jul 12;1(4):luad073. doi: 10.1210/jcemcr/luad073. eCollection 2023 Jul.

ABSTRACT

Adrenal cortical carcinoma (ACC) is a rare cancer (1-2/million) that presents with hormone overproduction in 60% of cases. Presentation of ACC with multiple hormone syndromes from different adrenal zones is rare. We present a case of dual-secreting ACC with hyperaldosteronism and cortisol excess. The previously healthy patient was noted to have new-onset hypertension and hypokalemia during a primary care visit. On hormonal evaluation, he was found to have evidence of hyperaldosteronism and adrenocorticotropic hormone (ACTH)-independent cortisol excess. Imaging revealed a 2.7 × 3.1 × 3.5 cm left adrenal mass with indeterminant computed tomography characteristics. He underwent laparoscopic adrenalectomy and required glucocorticoid replacement for adrenal insufficiency postoperatively. Pathology revealed stage T2N0M0 ACC. His hypokalemia resolved and glucocorticoids were stopped within a month. This case stresses the importance of routine screening for cortisol excess in all adrenal masses detected on imaging. Avoidance of postoperative adrenal insufficiency in patients with cortisol excess without overt Cushing syndrome is paramount.

PMID:37909000 | PMC:PMC10580411 | DOI:10.1210/jcemcr/luad073

Permalink for 'Emerging Potential of Microwave Ablation for Primary Aldosteronism Resulting From Unilateral Aldosterone-producing Adenoma'

Emerging Potential of Microwave Ablation for Primary Aldosteronism Resulting From Unilateral Aldosterone-producing Adenoma

Fetched: November 2nd, 2023, 5:00am GMT by Edouard G Mills

JCEM Case Rep. 2023 Jul 12;1(4):luad077. doi: 10.1210/jcemcr/luad077. eCollection 2023 Jul.

ABSTRACT

Primary aldosteronism (PA) is the most prevalent form of secondary hypertension and is most commonly caused by an adrenal adenoma or bilateral adrenal hyperplasia. Minimally invasive adrenalectomy is the treatment of choice for unilateral disease. Here, we report the case of a 57-year-old man with previous bladder cancer who was referred for evaluation of resistant hypertension and hypokalemia. Diagnostic workup indicated PA with computed tomography imaging revealing a left adrenal adenoma and adrenal venous sampling lateralizing to the left adrenal. He was therefore referred for a left adrenalectomy using a retroperitoneoscopic approach. However, surgery was complicated by significant perinephritis related to previous bladder cancer immunotherapy and, in view of an identifiable adrenal adenoma, a partial adrenalectomy was performed. Despite histology confirming removal of an adrenal adenoma, he remained hypertensive and hypokalemic with persistent PA. He underwent a computed tomography-guided percutaneous thermal (microwave) ablation of the residual adrenal nodule with immediate biochemical reversal of PA. Six years postprocedure, he remains biochemically and clinically cured from PA. This article presents the details of the case and reviews the literature on long-term outcomes for patients undergoing thermal ablation and adrenalectomy, suggesting that thermal ablation may be a viable alternative for selected patients.

PMID:37908986 | PMC:PMC10580483 | DOI:10.1210/jcemcr/luad077

Massive Biochemically Silent Pheochromocytoma Masquerading as Nonfunctioning Adrenocortical Cancer

Fetched: November 2nd, 2023, 5:00am GMT by Shejil Kumar

JCEM Case Rep. 2023 Jun 7;1(3):luad061. doi: 10.1210/jcemcr/luad061. eCollection 2023 May.

ABSTRACT

Pheochromocytomas are rare catecholamine-secreting neuroendocrine tumors of the adrenal medulla chromaffin cells, usually associated with features of catecholamine excess. Clinically and biochemically silent pheochromocytoma without adrenergic symptoms or elevated catecholamine concentrations are rare. A 71-year-old female presented with acute right flank pain with abdominal computed tomography (CT) scan revealing a hemorrhagic right adrenal mass. She had no preceding adrenergic symptoms, and normal serum electrolytes, on a background of well-controlled hypertension on amlodipine monotherapy. After conservative management and discharge, an outpatient CT adrenal scan confirmed an 88 × 64 mm right adrenal mass demonstrating intense avidity (maximum standardized uptake value, 20.2) on fluorodeoxyglucose F 18-positron emission tomography (FDG-PET)/CT scan. Biochemical screening supported a nonfunctional adrenal lesion with normal-range plasma normetanephrines and metanephrines. She underwent a right adrenalectomy for presumed nonfunctioning adrenocortical cancer; however, histopathology demonstrated a 120-mm pheochromocytoma. Succinate dehydrogenase subunit B (SDHB) and fumarate hydratase (FH) staining were retained; however, weakly positive 2SC staining raised concerns for FH-deficient pheochromocytoma. Germline DNA sequencing was negative for pathogenic RET, VHL, SDHB, SDHD, or FH variants. Tumor cells stained positive for tyrosine hydroxylase and negative for dopamine β hydroxylase. Four months postoperatively, progress FDG-PET/CT scan demonstrated no focal avidity. Massive biochemically silent pheochromocytomas are exceedingly rare, and we discuss various mechanisms that may predispose patients to this phenomenon.

PMID:37908587 | PMC:PMC10580479 | DOI:10.1210/jcemcr/luad061

Marked Hypoleptinemia Precedes Overt Fat Loss in Immune Checkpoint Inhibitor-induced Acquired Generalized Lipodystrophy

Fetched: November 2nd, 2023, 5:00am GMT by Maheswaran Dhanasekaran

JCEM Case Rep. 2023 Mar 9;1(2):luad025. doi: 10.1210/jcemcr/luad025. eCollection 2023 Mar.

ABSTRACT

Immune checkpoint inhibitors (ICIs) targeting cancer cells that evade immune T-cell regulation have revolutionized the treatment of metastatic carcinomas. Unfortunately, secondary endocrinopathies associated with ICI, including adrenal insufficiency, primary hypothyroidism, autoimmune diabetes, and rarely hypoparathyroidism, are increasing. Lipodystrophy, presumably due to the autoimmune destruction of adipocytes, leading to metabolic complications, is a less recognized adverse effect of ICI therapy. We present a case of a 66-year-old Caucasian woman treated with pembrolizumab, an anti-programmed death 1 inhibitor, for metastatic lung adenocarcinoma. Fifteen months after the treatment initiation, she was found to have hyperglycemia, hyperlipidemia, and hepatic steatosis but without any evidence of autoimmune diabetes. She was also noted to have isolated buccal fat pad loss, raising suspicion of acquired lipodystrophy. Despite well-preserved subcutaneous fat over the trunk and limbs, she had undetectable serum leptin levels. Whole-body fluorodeoxyglucose (FDG)-positron emission tomography scan showed diffuse mild FDG activity throughout the subcutaneous tissue, suggesting underlying inflammation. Over the next 3 months, she developed progressive fat loss leading to generalized lipodystrophy. Adipose tissue dysfunction, secondary to ICI-induced subclinical panniculitis, precedes overt fat loss and is characterized by hypoleptinemia and metabolic abnormalities.

PMID:37908472 | PMC:PMC10580409 | DOI:10.1210/jcemcr/luad025

Colon Cancer Presenting as Pituitary Mass and Hypopituitarism: Recognition and Multidisciplinary Approach of a Rare Case

Fetched: November 2nd, 2023, 5:00am GMT by Flavia Costanza

JCEM Case Rep. 2023 Apr 21;1(2):luad031. doi: 10.1210/jcemcr/luad031. eCollection 2023 Mar.

ABSTRACT

Pituitary metastases are rare. Until now, few cases have been reported; about 50% of pituitary metastases originate from breast or lung cancers. We describe the clinical case of a primary colon carcinoma first presenting with a pituitary metastasis. A 76-year-old woman, with no history of malignancy, presented with headache, dizziness, and diplopia, at the Emergency Department. The neurologic examination was remarkable for complete left ophthalmoplegia with sensitivity deficit on the left side of the face. Radiologic investigations documented a voluminous sellar and suprasellar lesion, with extension in the left cavernous sinus and temporal lobe. Pituitary hormone levels were suggestive of anterior hypopituitarism and mild hyperprolactinemia. Subtotal surgical removal of the lesion was achieved through a trans-sphenoidal endoscopic endonasal approach. The histological examination disclosed a metastasis of gastrointestinal adenocarcinoma. A subsequent colonoscopy identified right colon cancer. A contrasted total-body computerized tomography ruled out other metastases. Postsurgical MRI showed a stable parasellar residual tumor. Conventional radiotherapy was scheduled. This case underlines the importance of considering pituitary metastases in the differential diagnosis of aggressive pituitary lesions, which should be managed in a pituitary tumor center of excellence through a multidisciplinary approach, for the complexity in diagnosis and therapeutic management of this rare condition.

PMID:37908471 | PMC:PMC10580474 | DOI:10.1210/jcemcr/luad031

Abiraterone-Induced Endocrinopathies

Fetched: November 2nd, 2023, 5:00am GMT by Scarlett Decamps

JCEM Case Rep. 2023 Apr 13;1(2):luad039. doi: 10.1210/jcemcr/luad039. eCollection 2023 Mar.

ABSTRACT

Abiraterone, a CYP17A1 inhibitor, is used along with prednisone in patients with castration-resistant and castration-sensitive prostate cancer, yielding improved overall and disease-free survival. However, little is documented in the endocrinology literature about the incidences of the endocrine side effects of abiraterone. In this case series, we discuss the diagnosis and management of 3 prostate cancer patients who experienced mineralocorticoid excess and secondary adrenal insufficiency related to abiraterone and prednisone use.

PMID:37908462 | PMC:PMC10580404 | DOI:10.1210/jcemcr/luad039

MEN1 in a Patient With Nonsyndromic Familial Nonmedullary Thyroid Carcinoma

Fetched: November 2nd, 2023, 5:00am GMT by Lauren A Fitzgerald

JCEM Case Rep. 2022 Nov 30;1(1):luac019. doi: 10.1210/jcemcr/luac019. eCollection 2023 Jan.

ABSTRACT

Clinical syndromes involving multiple endocrine glands have been well recognized for over a century. Multiple reports describing hereditary multiple endocrine neoplasia (MEN) syndromes involving pituitary, parathyroid, and pancreatic neuroendocrine tumors have been published. Differentiated (nonmedullary) thyroid cancer can also present as a hereditary syndrome with or without a specific genetic predisposition. We report the case of a man with nonsyndromic familial nonmedullary thyroid carcinoma, a pituitary adenoma, hyperparathyroidism, an adrenal adenoma, and pancreatic adenocarcinoma. Genetic testing did not reveal mutations in the commonly reported genes associated with MEN syndromes. MEN1 is characterized by endocrine neoplasia in at least 2 of the following glands: pituitary, parathyroid, and the gastro-entero-pancreatic (GEP) tract. Co-occurrence of MEN1 with familial nonmedullary thyroid carcinoma, however, has not been reported in the medical literature. This unique case of MEN1 co-existing in a patient with nonsyndromic familial thyroid carcinoma was not associated with any common MEN syndrome germline mutations.

PMID:37908266 | PMC:PMC10578386 | DOI:10.1210/jcemcr/luac019

Pseudo Primary Aldosteronism as Initial Presentation of Ectopic ACTH Syndrome in Metastatic Small Cell Lung Cancer

Fetched: November 2nd, 2023, 5:00am GMT by Jonathan Shakesprere

JCEM Case Rep. 2022 Nov 30;1(1):luac020. doi: 10.1210/jcemcr/luac020. eCollection 2023 Jan.

ABSTRACT

Ectopic adrenocorticotropic hormone (ACTH)-secreting syndrome (EAS) is a rare but often aggressive paraneoplastic syndrome. Patients with EAS typically present with high ACTH levels and rapid clinical progression in the setting of acute cortisol elevation, which can delay diagnosis due to a lack of typical Cushingoid features. High levels of ACTH have also been shown to stimulate the adrenal zona glomerulosa to oversecrete aldosterone. We present the case of a 58-year-old male individual presenting with new-onset hypertension and severe metabolic alkalosis with spontaneous hypokalemia, in the setting of elevated aldosterone and low renin levels, suggestive of primary aldosteronism. Subsequent biochemical testing, imaging, and pathology, however, revealed suppression of aldosterone with evidence of hypercortisolism in the setting of metastatic small cell lung cancer. This was, therefore, suggestive of pseudo primary aldosteronism in the setting of a paraneoplastic ectopic ACTH-producing syndrome. This case highlights that hypercortisolism, in the setting of EAS, can initially present with a clinical picture suggestive of hyperaldosteronism. The use of a dexamethasone suppression test can allow the clinician to differentiate between idiopathic bilateral adrenal hyperplasia and ectopic ACTH syndrome.

PMID:37908248 | PMC:PMC10578378 | DOI:10.1210/jcemcr/luac020

Permalink for 'The connection between tricarboxylic acid cycle enzyme mutations and pseudohypoxic signaling in pheochromocytoma and paraganglioma'

The connection between tricarboxylic acid cycle enzyme mutations and pseudohypoxic signaling in pheochromocytoma and paraganglioma

Fetched: November 2nd, 2023, 5:00am GMT by Yuxiong Wang

Front Endocrinol (Lausanne). 2023 Oct 5;14:1274239. doi: 10.3389/fendo.2023.1274239. eCollection 2023.

ABSTRACT

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors originating from chromaffin cells, holding significant clinical importance due to their capacity for excessive catecholamine secretion and associated cardiovascular complications. Roughly 80% of cases are associated with genetic mutations. Based on the functionality of these mutated genes, PPGLs can be categorized into distinct molecular clusters: the pseudohypoxia signaling cluster (Cluster-1), the kinase signaling cluster (Cluster-2), and the WNT signaling cluster (Cluster-3). A pivotal factor in the pathogenesis of PPGLs is hypoxia-inducible factor-2α (HIF2α), which becomes upregulated even under normoxic conditions, activating downstream transcriptional processes associated with pseudohypoxia. This adaptation provides tumor cells with a growth advantage and enhances their ability to thrive in adverse microenvironments. Moreover, pseudohypoxia disrupts immune cell communication, leading to the development of an immunosuppressive tumor microenvironment. Within Cluster-1a, metabolic perturbations are particularly pronounced. Mutations in enzymes associated with the tricarboxylic acid (TCA) cycle, such as succinate dehydrogenase (SDHx), fumarate hydratase (FH), isocitrate dehydrogenase (IDH), and malate dehydrogenase type 2 (MDH2), result in the accumulation of critical oncogenic metabolic intermediates. Notable among these intermediates are succinate, fumarate, and 2-hydroxyglutarate (2-HG), which promote activation of the HIFs signaling pathway through various mechanisms, thus inducing pseudohypoxia and facilitating tumorigenesis. SDHx mutations are prevalent in PPGLs, disrupting mitochondrial function and causing succinate accumulation, which competitively inhibits α-ketoglutarate-dependent dioxygenases. Consequently, this leads to global hypermethylation, epigenetic changes, and activation of HIFs. In FH-deficient cells, fumarate accumulation leads to protein succination, impacting cell function. FH mutations also trigger metabolic reprogramming towards glycolysis and lactate synthesis. IDH1/2 mutations generate D-2HG, inhibiting α-ketoglutarate-dependent dioxygenases and stabilizing HIFs. Similarly, MDH2 mutations are associated with HIF stability and pseudohypoxic response. Understanding the intricate relationship between metabolic enzyme mutations in the TCA cycle and pseudohypoxic signaling is crucial for unraveling the pathogenesis of PPGLs and developing targeted therapies. This knowledge enhances our comprehension of the pivotal role of cellular metabolism in PPGLs and holds implications for potential therapeutic advancements.

PMID:37867526 | PMC:PMC10585109 | DOI:10.3389/fendo.2023.1274239

Permalink for 'Laparoscopic excision of normotensive variant pheochromocytoma in a case of triple vessel coronary artery disease: The anaesthesia challenge'

Laparoscopic excision of normotensive variant pheochromocytoma in a case of triple vessel coronary artery disease: The anaesthesia challenge

Fetched: November 2nd, 2023, 5:00am GMT by Anitha Diwakar

Ann Card Anaesth. 2023 Oct-Dec;26(4):454-457. doi: 10.4103/aca.aca_14_23.

ABSTRACT

Pheochromocytomas are catecholamine-secreting tumours arising mostly from the adrenal medulla. With the advancement in surgical and anaesthetic techniques, the incidence of severe morbidity and mortality associated with surgery is low. However, concurrent coronary artery disease and pheochromocytoma continue to be a challenge due to the risk of adverse cardiovascular events. We describe the successful management of pheochromocytoma excision in a patient with coronary artery disease.

PMID:37861585 | DOI:10.4103/aca.aca_14_23

Pediatric adrenocortical carcinoma: clinical features and application of neoadjuvant chemotherapy

Fetched: November 2nd, 2023, 5:00am GMT by Yu Lin

Eur J Med Res. 2023 Oct 9;28(1):411. doi: 10.1186/s40001-023-01381-3.

ABSTRACT

OBJECTIVE: To summarize the clinical characteristics of children with adrenocortical carcinoma (ACC) and preliminarily explore the indications for and efficacy of neoadjuvant chemotherapy in certain patients.

METHODS: The data of 49 children with adrenocortical tumors (ACT) in the past 15 years were retrospectively analyzed, and after pathology assessment using Weiss system grading, 40 children diagnosed with ACC were included. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and three-dimensional (3D) reconstruction of contrast-enhanced computed tomography data were used to evaluate the response to neoadjuvant chemotherapy.

RESULTS: Forty patients (17 males, 23 females) with ACC were enrolled. Abnormal hormone levels were common in children with ACC (n = 31), and in terms of clinical presentation, sexual precocity was the most common (n = 14, 35.0%), followed by Cushing's syndrome (n = 12, 30.0%). Seven of 40 children received neoadjuvant chemotherapy due to a maximum lesion diameter greater than 10 cm (n = 4), invasion of surrounding tissues (n = 2), intravenous tumor thrombus (n = 2), and/or distant metastasis (n = 2); 2 patients achieved partial response, and 5 had stable disease according to the RECIST 1.1 standard. Furthermore, 3D tumor volume reconstruction was performed in 5 children before and after neoadjuvant chemotherapy. Tumor volumes were significantly reduced in all 5 children, with a median volume reduction of 270 (interquartile range, IQR 83, 293) (range: 49-413) ml. After surgery with/without chemotherapy, the 5-year overall survival rate for all children was 90.0% (95% CI-confidence interval 80.0-100.0%), and the 5-year event-free survival rate was 81.5% (95% CI 68.0-97.7%).

CONCLUSION: In the diagnosis and treatment of pediatric ACC, a comprehensive endocrine evaluation is necessary to facilitate early diagnosis. Surgery and chemotherapy are important components of ACC treatment, and neoadjuvant chemotherapy should be considered for children with ACC who meet certain criteria, such as a large tumor, distant metastases, or poor general condition.

PMID:37814272 | PMC:PMC10563212 | DOI:10.1186/s40001-023-01381-3

Editorial: A year in review: discussions in adrenal endocrinology

Fetched: November 2nd, 2023, 5:00am GMT by Ivana Kraljevic

Front Endocrinol (Lausanne). 2023 Sep 22;14:1291582. doi: 10.3389/fendo.2023.1291582. eCollection 2023.

NO ABSTRACT

PMID:37810878 | PMC:PMC10558014 | DOI:10.3389/fendo.2023.1291582

Permalink for 'Transperitoneal Laparoscopic Adrenalectomy for Metachronous Contralateral Adrenal Metastasis from Oligometastatic Renal Cell Cancer: Case Report and Review of the Literature'

Transperitoneal Laparoscopic Adrenalectomy for Metachronous Contralateral Adrenal Metastasis from Oligometastatic Renal Cell Cancer: Case Report and Review of the Literature

Fetched: November 1st, 2023, 5:00am GMT by Ercan Öğreden

Curr Med Imaging. 2023 Oct 23. doi: 10.2174/0115734056244676231016094516. Online ahead of print.

ABSTRACT

BACKGROUND: The definition of oligometastasis is still controversial. Cytoreductive nephrectomy and metastasectomy are important approaches in selected patients with oligometastasis for improving survival. We aimed to present our laparoscopic metastasectomy experience in a rare case of contralateral adrenal metastasis in an oligometastatic kidney tumor.

CASE REPORT: A 52-year-old male patient was admitted to our clinic with the diagnosis of an incidental right renal mass. On contrast-enhanced abdominal CT revealed a mass reaching approximately 8 cm in diameter in the right kidney located in the middle pole. On contrast-enhanced thorax, CT showed a metastatic lesion in the left main bronchus bifurcation. The patient underwent an open radical nephrectomy with the diagnosis of an oligometastatic right renal mass. His pathology was reported as clear cell renal cell carcinoma (ccRCC). The patient was referred to the medical oncology clinic for immunotherapy. The metastatic lesion in the lung completely regressed in the follow-up of the patient who was started on Chek point inhibitors. However, he was referred to our clinic after an incidental metachronous mass was detected in the contralateral left adrenal in FDG PET/CT (SUVmax: 6.7) in 1st year. Dynamic contrast-enhanced MRI was performed to reevaluate and for mass characterization, and a 4 cm mass was observed in the left contralateral adrenal. Laparoscopic metastasectomy was performed for the left adrenal mass. No recurrence or adrenal insufficiency developed in the 6-month follow-up after discharge.

CONCLUSION: Transperitoneal adrenalectomy is a minimally invasive method that can be safely performed in metastatic adrenal masses. Although contralateral adrenal metastasis is rare in ccRCC, it should be kept in mind that adrenal metastasis may develop in the late period in patients with a history of renal cancer.

PMID:37904565 | DOI:10.2174/0115734056244676231016094516

The Impact of the COVID Pandemic on Adrenal Surgery at an Academic Endocrine Surgery Unit

Fetched: October 31st, 2023, 5:00am GMT by Costanza Chiapponi

Horm Metab Res. 2023 Nov;55(11):765-770. doi: 10.1055/a-2187-3547. Epub 2023 Oct 30.

ABSTRACT

COVID-19 has severely affected the delivery of surgical care worldwide. The aim of the present study was to evaluate its impact on adrenal surgery at our academic endocrine center. All primary adrenal surgeries performed at the University Hospital of Cologne, Germany between 01.01.2019 and 31.07.2022 were included. This time frame was divided into pre-Covid (before 02/20), acute Covid (until 05/21), and post acute period (after 05/2021). Demographics, clinic-pathologic characteristics and treatment of these patients were analyzed. One hundred adrenalectomies were included: 22 before, 30 during, and 48 after the acute phase. The percentage of Conn adenomas and pheochromocytomas decreased during the acute phase (from 45.4 to 26.6% and from 18 to 10%, respectively) in favor of Cushing adenomas and suspicious tumors (from 4.5 to 20% and from 31.8 to 36.6%). About 90.9% of tumors resected for suspicion of malignancy were confirmed malignant by final histopathology, as opposed to 71.4% and 52.6% before and after the acute phase. The operative technique was similar during the three phases (63% retroperitoneoscopic, 34% laparoscopic and 2% open resections), with a significantly shorter operative time for retroperitoneoscopy (p=0.04). ICU monitoring demand increased during the acute phase (from 13.6% to 43.3%), according to the increase in Cushing adenomas and malignant tumors. During the acute phase of COVID-19 pandemic adrenal surgery for Cushing and malignant tumors increased, while a delay in pheochromocytoma surgery to the post acute phase was observed. The suspicion of malignancy formulated by the endocrine tumor board was accurate in 90.9% of cases.

PMID:37903497 | DOI:10.1055/a-2187-3547

Regulation of epinephrine biosynthesis in HRAS-mutant paragangliomas

Fetched: October 31st, 2023, 5:00am GMT by Minghao Li

Endocr Relat Cancer. 2023 Oct 30;30(12):e230230. doi: 10.1530/ERC-23-0230. Print 2023 Dec 1.

ABSTRACT

The biochemical phenotype of paragangliomas (PGLs) is highly dependent on the underlying genetic background and tumor location. PGLs at extra-adrenal locations usually do not express phenylethanolamine N-methyltransferase (PNMT), the enzyme required for epinephrine production, which was explained by the absence of glucocorticoids. PGLs with pathogenic variants (PVs) in Harvey rat sarcoma viral oncogene homolog (HRAS) can occur in or outside of the adrenal, but always synthesize epinephrine independently of the localization. Here, we characterize the signaling pathways through which PVs in HRAS influence PNMT expression. Catecholamines, cortisol, and transcriptional features of PGL tissues with known genetic background were analyzed. Genetically modified rat pheochromocytoma cells carrying PVs in Hras were generated and analyzed for regulation of Pnmt expression. Elevated epinephrine contents in PGLs with PVs in HRAS were accompanied by enrichment in mitogen-activated protein kinase (MAPK) signaling compared to PGLs with PVs in genes that activate hypoxia pathways. In vitro, Hras PVs increased Pnmt expression and epinephrine biosynthesis through increased phosphorylation of stimulatory protein 1 via MAPK signaling. Here, we provide a molecular mechanism that explains the PV-dependent epinephrine production of PGLs.

PMID:37902037 | DOI:10.1530/ERC-23-0230

Primary adrenal Ewing sarcoma: A systematic review of the literature

Fetched: October 31st, 2023, 5:00am GMT by Dimitrios K Manatakis

World J Clin Cases. 2023 Oct 6;11(28):6782-6791. doi: 10.12998/wjcc.v11.i28.6782.

ABSTRACT

BACKGROUND: Ewing sarcoma (ES) is a malignant neoplasm of neuroectodermal origin and is commonly observed in children and young adults. The musculoskeletal system is the main body system impacted and ES is rarely seen in the visceral organs particularly the adrenal gland.

AIM: To present a comprehensive review of primary adrenal ES, with emphasis on diagnosis, therapy and oncological outcomes.

METHODS: A systematic review of the literature was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020. PubMed/ MEDLINE, EMBASE and Google Scholar bibliographic databases were searched to identify articles from 1989 to 2022 and included patients with ES/primitive neuroectodermal tumor (PNET) of the adrenal gland. PubMed, Google Scholar and EMBASE medical databases were searched, combining the terms "adrenal", "ES" and "PNET". Demographic, clinical, pathological and oncological data of patients were analyzed by SPSS version 29.0.

RESULTS: A total of 52 studies were included for review (47 case reports and 5 case series) with 66 patients reported to have primary adrenal ES. Mean age at diagnosis was 26.4 ± 15.4 years (37.9% males, 57.6% females, sex not reported in 3 cases). The most frequent complaint was abdominal/flank pain or discomfort (46.4%) followed by a palpable mass (25.0%), and the average duration of symptoms was 2.6 ± 3.1 mo. The imaging modality of choice was computed tomography scan (81.5%), followed by magnetic resonance imaging (20.4%). Preoperative staging revealed that 17 tumors (27.9%) were metastatic and 14 patients had inferior vena cava or renal vein neoplastic thrombus at initial diagnosis. Open adrenalectomy was performed in the majority of cases (80.0%), of which 27.9% required more extensive resection. Minimally invasive surgery was attempted in 8.2% of tumors. Complete surgical resection was achieved in 89.4% of the patients. Adjuvant therapy was administered to 32 patients, in the form of chemotherapy (62.5%), radiotherapy (3.1%) or combination (34.4%). Median overall survival was 15 mo and 24-mo overall survival was 40.5%. Median disease-free survival was 10 mo and 24-mo disease-free survival was 33.3%.

CONCLUSION: The significant progress in molecular biology and genetics of ES does not reflect on patient outcomes. ES remains an aggressive tumor with a poor prognosis and high mortality.

PMID:37900999 | PMC:PMC10600854 | DOI:10.12998/wjcc.v11.i28.6782

Feminizing Adrenocortical Tumor with Multiple Recurrences: A Case Report

Fetched: October 31st, 2023, 5:00am GMT by Joseph M Rich

Case Rep Oncol. 2023 Sep 26;16(1):1033-1040. doi: 10.1159/000533835. eCollection 2023 Jan-Dec.

ABSTRACT

Feminizing adrenocortical tumors (FATs) are exceptionally rare primary adrenal neoplasms that cause high estrogen and low testosterone levels. They are most common in adult males, typically presenting with gynecomastia, hypogonadism, and weight loss. They are almost always malignant, with a poor prognosis and a high recurrence rate. We report a case of a 35-year-old man with an adrenal FAT with high estrogen (181 pg/mL) and low testosterone (37 ng/dL) who presented with gynecomastia, erectile dysfunction, subclinical Cushing syndrome, and pain localizing to different regions of the torso. There was no evidence of metastatic disease initially as seen by visualization of a well-marginated mass on computed tomography scan. Surgical resection of the FAT was performed, and the mass was confirmed to be a low-grade tumor. Clinical symptoms were resolved after surgery. Despite complete resection with negative margins, the patient subsequently had two separate local metastatic recurrences within a few years, treated with a combination of further surgery and medical intervention. This case highlights the unique features of an exceedingly rare adrenal tumor and stresses the importance of early detection and vigilant surveillance following resection due to high recurrence rates.

PMID:37900824 | PMC:PMC10601808 | DOI:10.1159/000533835

Permalink for 'Acanthosis Nigricans in a Patient with Urothelial Carcinoma Treated with PD-L1 Inhibitor Avelumab, and Secondary Adrenal Insufficiency'

Acanthosis Nigricans in a Patient with Urothelial Carcinoma Treated with PD-L1 Inhibitor Avelumab, and Secondary Adrenal Insufficiency

Fetched: October 31st, 2023, 5:00am GMT by Fei Ya Lai

Case Rep Oncol. 2023 Oct 16;16(1):1107-1112. doi: 10.1159/000533758. eCollection 2023 Jan-Dec.

ABSTRACT

Acanthosis nigricans (AN) describes hyperkeratotic and hyperpigmented skin changes and its pathophysiology is linked to the activation of epidermal growth factor receptors. Current literature shows that AN is most commonly diagnosed at the time of the underlying pathology, which may occur under benign or malignant conditions. This case presentation demonstrates the occurrence of AN in a patient following the diagnosis of urothelial carcinoma and ongoing treatment with PD-L1 inhibitor immunotherapy. Subsequent investigations ruled out a secondary malignancy or disease progression; however, metabolic screening identified secondary glucocorticoid induced adrenal insufficiency. AN was persistent in this patient despite adequate treatment, which highlights its co-occurrence in both benign and paraneoplastic conditions.

PMID:37900822 | PMC:PMC10601793 | DOI:10.1159/000533758

A Chromosome 9p24.1 Amplification in Colorectal Cancer with Metastases to the Kidney and Adrenal Gland: A Case Report

Fetched: October 31st, 2023, 5:00am GMT by Ana Paric

Case Rep Oncol. 2023 Sep 4;16(1):803-810. doi: 10.1159/000533377. eCollection 2023 Jan-Dec.

ABSTRACT

Colorectal cancer (CRC) is the third leading cause of mortality worldwide. The Food and Drug Administration recently designated pembrolizumab, an immune checkpoint inhibitor (ICI) against a programmed death-1 receptor, as a breakthrough drug for the treatment of patients with mCRC whose tumors have deficient mismatch-repair gene expression (as evidenced by microsatellite instability-high) and patients with solid tumors with a high tumor mutational burden with ≥10 mutations/megabase. We present a patient with metastatic CRC having renal and adrenal gland metastases. Comprehensive molecular profiling performed on a site of metastatic CRC in the kidney revealed multiple genomic alterations characteristic of CRC and rare chromosome 9p24.1 amplification, resulting in a co-amplification of the PDL1, PDL2, and JAK2 genes. Although this genomic alteration may predict the response to ICI, the lack of pembrolizumab prevented the patient from receiving targeted treatment and succumbing to the disease.

PMID:37900784 | PMC:PMC10601774 | DOI:10.1159/000533377

Permalink for 'Identification of Molecular Subtypes and Prognostic Characteristics of Adrenocortical Carcinoma Based on Unsupervised Clustering'

Identification of Molecular Subtypes and Prognostic Characteristics of Adrenocortical Carcinoma Based on Unsupervised Clustering

Fetched: October 31st, 2023, 5:00am GMT by Yuan Zhang

Int J Mol Sci. 2023 Oct 23;24(20):15465. doi: 10.3390/ijms242015465.

ABSTRACT

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a poor prognosis. Increasing evidence highlights the significant role of immune-related genes (IRGs) in ACC progression and immunotherapy, but the research is still limited. Based on the Cancer Genome Atlas (TCGA) database, immune-related molecular subtypes were identified by unsupervised consensus clustering. Univariate Cox analysis and Least Absolute Shrinkage and Selection Operator (LASSO) regression were employed to further establish immune-related gene signatures (IRGS). An evaluation of immune cell infiltration, biological function, tumor mutation burden (TMB), predicted immunotherapy response, and drug sensitivity in ACC patients was conducted to elucidate the applicative efficacy of IRGS in precision therapy. ACC patients were divided into two molecular subtypes through consistent clustering. Furthermore, the 3-gene signature (including PRKCA, LTBP1, and BIRC5) based on two molecular subtypes demonstrated consistent prognostic efficacy across the TCGA and GEO datasets and emerged as an independent prognostic factor. The low-risk group exhibited heightened immune cell infiltration, TMB, and immune checkpoint inhibitors (ICIs), associated with a favorable prognosis. Pathways associated with drug metabolism, hormone regulation, and metabolism were activated in the low-risk group. In conclusion, our findings suggest IRGS can be used as an independent prognostic biomarker, providing a foundation for shaping future ACC immunotherapy strategies.

PMID:37895143 | PMC:PMC10607826 | DOI:10.3390/ijms242015465

Permalink for 'Early short-term effects on catecholamine levels and pituitary function in patients with pheochromocytoma or paraganglioma treated with [177Lu]Lu-DOTA-TATE therapy'

Early short-term effects on catecholamine levels and pituitary function in patients with pheochromocytoma or paraganglioma treated with [177Lu]Lu-DOTA-TATE therapy

Fetched: October 31st, 2023, 5:00am GMT by Sriram Gubbi

Front Endocrinol (Lausanne). 2023 Oct 11;14:1275813. doi: 10.3389/fendo.2023.1275813. eCollection 2023.

ABSTRACT

PURPOSE: While there are reports of treatment-related endocrine disruptions and catecholamine surges in pheochromocytoma/paraganglioma (PPGL) patients treated with [¹⁷⁷Lu]Lu-DOTA-TATE therapy, the spectrum of these abnormalities in the immediate post-treatment period (within 48 hours) has not been previously evaluated and is likely underestimated.

METHODS: The study population included patients (≥18 years) enrolled in a phase 2 trial for treatment of somatostatin receptor (SSTR)-2+ inoperable/metastatic pheochromocytoma/paraganglioma with [¹⁷⁷Lu]Lu-DOTA-TATE (7.4 GBq per cycle for 1 - 4 cycles). Hormonal measurements [adrenocorticotropic hormone (ACTH), cortisol, thyroid stimulating hormone (TSH), free thyroxine (FT4), follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, estradiol, growth hormone, prolactin], catecholamines, and metanephrines were obtained on days-1, 2, 3, 30, and 60 per cycle as per trial protocol, and were retrospectively analyzed.

RESULTS: Among the 27 patients (age: 54 ± 12.7 years, 48.1% females) who underwent hormonal evaluation, hypoprolactinemia (14.1%), elevated FSH (13.1%), and elevated LH (12.5%) were the most frequent hormonal abnormalities across all 4 cycles combined. On longitudinal follow-up, significant reductions were noted in i. ACTH without corresponding changes in cortisol, ii. TSH, and FT4, and iii. prolactin at or before day-30 of [¹⁷⁷Lu]Lu-DOTA-TATE. No significant changes were observed in the gonadotropic axis and GH levels. Levels of all hormones on day-60 were not significantly different from day-1 values, suggesting the transient nature of these changes. However, two patients developed clinical, persistent endocrinopathies (primary hypothyroidism: n=1 male; early menopause: n=1 female). Compared to day-1, a significant % increase in norepinephrine, dopamine, and normetanephrine levels were noted at 24 hours following [¹⁷⁷Lu]Lu-DOTA-TATE dose and peaked within 48 hours.

CONCLUSIONS: [¹⁷⁷Lu]Lu-DOTA-TATE therapy is associated with alterations in endocrine function likely from radiation exposure to SSTR2+ endocrine tissues. However, these changes may sometimes manifest as clinically significant endocrinopathies. It is therefore important to periodically assess endocrine function during [¹⁷⁷Lu]Lu-DOTA-TATE therapy, especially among symptomatic patients.

CLINICAL TRIAL REGISTRATION: [https:] identifier NCT03206060.

PMID:37886645 | PMC:PMC10598842 | DOI:10.3389/fendo.2023.1275813

Primary aldosteronism 2.0: an update for clinicians on diagnosis and treatment

Fetched: October 28th, 2023, 5:00am GMT by Stefan Pilz

Pol Arch Intern Med. 2023 Oct 26;133(10):16585. doi: 10.20452/pamw.16585. Epub 2023 Oct 11.

ABSTRACT

Primary aldosteronism (PA), characterized by inappropriately high concentrations of the adrenal-derived hormone aldosterone, is the most common endocrine cause of arterial hypertension. As compared with individuals with essential hypertension, patients with PA have a significantly increased cardiovascular risk that cannot be fully reversed by common antihypertensive treatment because of blood pressure-independent deleterious effects of aldosterone. Measurement of the aldosterone to renin ratio (ARR), reflecting the degree of aldosterone excess, is the classic screening test for PA, but thresholds for an elevated ARR vary substantially and are arbitrary, as there exists a wide disease continuum that spans from preclinical stages to overt PA. Treatment approaches for PA with either mineralocorticoid receptor antagonists for bilateral disease or unilateral adrenalectomy for aldosterone-producing adenomas (APA) are highly effective to mitigate the excess cardiovascular risk associated with PA. Subtype classification according to the dichotomous concept of unilateral PA, mainly due to APAs, vs bilateral PA, mainly due to bilateral adrenal hyperplasia, has been recently challenged by advances in the pathophysiologic understanding and therapeutic spectrum of PA. The implementation of current PA guidelines into clinical routine is extremely poor, as reflected by the fact that most patients suffering from PA remain undiagnosed and probably untreated. Pragmatic approaches are required to address this public health problem. In this review, we present an up‑to‑date overview on the clinical significance, diagnosis, and treatment of PA, with the aim to provide guidance for clinicians regarding the management of this disease, paying particular attention to its feasible implementation into daily clinical routine.

PMID:37818947 | DOI:10.20452/pamw.16585

An unusual presentation of a primary lung adenocarcinoma: A case report

Fetched: October 27th, 2023, 5:00am GMT by Callie Killoran

Int J Surg Case Rep. 2023 Oct 24;112:108967. doi: 10.1016/j.ijscr.2023.108967. Online ahead of print.

ABSTRACT

INTRODUCTION AND IMPORTANCE: Lung cancer is one of the most common malignancies worldwide and common sites of metastasis are to brain, liver, adrenal glands, and bones [1]. Metastasis to the gastrointestinal (GI) tract is extremely rare (<1%) and the most common site is the small intestine [5].

CASE PRESENTATION: A 60-year-old female referred for intermittent colicky abdominal pain and diarrhoea, with cross-sectional imaging showing a distal small bowel mass with lymphadenopathy. Malignancy workup revealed an additional mediastinal mass and raised tumour marker carcinoembryonic antigen (CEA). Bronchoscopy confirmed primary lung adenocarcinoma of the mediastinal mass. Given the raised CEA, evolving obstructive symptoms, and concerns for synchronous lung and gastrointestinal primaries, the patient proceeded to have a small bowel resection leading to the diagnosis of a GI lung metastasis.

CLINICAL DISCUSSION: If Symptomatic, suggested treatment of lung metastasis to the GI tract is surgical resection. Current evidence suggests that in isolated GI metastases, resection may have a therapeutic benefit and an association with overall survival rate.

CONCLUSION: In patients with symptomatic or isolated GI lung metastasis, surgical resection should be considered for treatment and management of metastatic disease. The role of tumour marker CEA in primary lung adenocarcinoma is unclear.

PMID:37883873 | DOI:10.1016/j.ijscr.2023.108967

The role of corticosteroids in the palliation of dyspnea in cancer patients: an evidence-based review

Fetched: October 27th, 2023, 5:00am GMT by David Hui

Curr Opin Support Palliat Care. 2023 Dec 1;17(4):270-276. doi: 10.1097/SPC.0000000000000677. Epub 2023 Sep 29.

ABSTRACT

PURPOSE OF REVIEW: To provide an evidence-based review on the use of corticosteroids for dyspnea in cancer patients.

RECENT FINDINGS: Corticosteroids are commonly used for palliation of dyspnea; however, there is wide variation in how they are prescribed due to the paucity of high-quality evidence. Some clinicians would offer corticosteroids routinely regardless of the causes of dyspnea, while others would only prescribe corticosteroids selectively for specific indications, such as lymphangitic carcinomatosis, upper airway obstruction, superior vena cava obstruction, and cancer treatment-induced pneumonitis. Few mechanistic studies have been conducted to support the use of corticosteroids in cancer patients. Two double-blind, placebo-controlled randomized trials have examined the routine use of high-dose dexamethasone for dyspnea in cancer patients. A pilot study suggested some benefits, but the larger confirmatory trial revealed no improvement compared to the placebo and significantly more adverse events. The selective use of corticosteroids use is only based on observational studies such as case series.

SUMMARY: The unfavorable risk:benefit ratio of high-dose dexamethasone suggests that it should not be routinely prescribed for dyspnea in cancer patients. More research is needed to assess the selective use of corticosteroids and identify patients most likely be benefit from corticosteroid use.

PMID:37773042 | DOI:10.1097/SPC.0000000000000677

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

Posted: November 21st, 2023, 3:00am GMT

Adebelizumab Combined With Chemotherapy and Radiotherapy Treat ES-SCLC

Posted: November 9th, 2023, 3:00am GMT

Conditions: Extensive Small Cell Lung Cancer
Interventions: Drug: Adebelizumab+Carboplatin+Etoposide+Concurrent Radiotherapy
Sponsors: Qianfoshan Hospital
Recruiting

Clinical and Genetic Investigation of the Association Between Primary Aldosteronism and Thyroid Cancer

Posted: October 5th, 2023, 2:00am GMT

Study of Radiotherapy and Pembrolizumab in People With Adrenocortical Carcinoma

Posted: October 4th, 2023, 2:00am GMT

Surgical Treatment of Adrenal Diseases- Laparoscopic vs. Robotic-assisted Adrenalectomy

Posted: September 22nd, 2023, 2:00pm GMT

Antibody Drug Conjugate ADCT-701 in Neuroendocrine Tumors and Carcinomas

Posted: September 18th, 2023, 2:00pm GMT

Cabozantinib in Combination With Atezolizumab for the Treatment of Patients With Locally Advanced, Metastatic, or Unresectable Adrenal Cortical Cancer

Posted: August 23rd, 2023, 2:00pm GMT

Phase 1 Study of 68Ga-R8760

Posted: August 21st, 2023, 2:00pm GMT

Conditions: Adrenocortical Carcinoma
Interventions: Drug: 68Ga-R8760 injection at pre-defined dose levels; Drug: 68Ga-R8760 injection
Sponsors: Radionetics Oncology
Recruiting

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

Posted: June 22nd, 2023, 2:00pm GMT

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

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

Posted: May 23rd, 2023, 2:00pm GMT

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

The Adverse Event of Mitotane Therapy in Patients With Adrenocortical Carcinoma

Posted: May 2nd, 2023, 2:00pm GMT

Condition: Adrenocortical Carcinoma
Intervention:
Sponsor: Shanghai Jiao Tong University School of Medicine
Not yet recruiting

European Multicenter Study on Role of Lymph Node Dissection in Surgical Management of Adrenal Cortical Carcinoma

Posted: March 10th, 2023, 3:00pm GMT

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

Posted: March 6th, 2023, 3:00pm GMT

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, 3:00pm GMT

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

A Study of Nivolumab, Ipilimumab, and Chemotherapy in Participants With Non-small Cell Lung Cancer

Posted: October 31st, 2022, 2:00am GMT

Conditions: Carcinoma, Non-Small-Cell Lung
Sponsors: Bristol-Myers Squibb
Recruiting

Pembrolizumab in the Treatment of Advanced, Progressive Adrenocortical Carcinoma.

Posted: October 3rd, 2022, 2:00pm GMT

Condition: Adrenocortical Carcinoma
Intervention: Drug: Pembrolizumab 25 MG/ML [Keytruda]
Sponsors: Maria Sklodowska-Curie National Research Institute of Oncology; Biostat Sp. z o.o.
Recruiting

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

Posted: February 14th, 2022, 3:00pm GMT

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

Phase II Trial of Pembrolizumab Plus Lenvatinib in Advanced Adrenal Cortical Carcinoma

Posted: September 5th, 2021, 2:00am GMT

Conditions: Adrenocortical Carcinoma
Interventions: Drug: Pembrolizumab / Lenvatinib
Sponsors: National Cancer Center, Korea; MSD Korea Ltd.
Enrolling by invitation

Milademetan in Advanced/Metastatic Solid Tumors

Posted: August 19th, 2021, 2:00pm GMT

Stereotactic MRI-guided Adaptive Radiation Therapy (SMART) in One Fraction

Posted: June 25th, 2021, 2:00pm GMT

Condition: Metastatic Carcinoma
Intervention: Radiation: Stereotactic ablative body radiation therapy
Sponsors: Baptist Health South Florida; Viewray Inc.
Recruiting

B7-H3-Specific Chimeric Antigen Receptor Autologous T-Cell Therapy for Pediatric Patients With Solid Tumors (3CAR)

Posted: May 21st, 2021, 2:00pm GMT

Anti-CTLA4-NF mAb (BMS986218), Nivolumab, and Stereotactic Body Radiation Therapy for the Treatment of Metastatic Solid Malignancies

Posted: March 5th, 2021, 3:00am GMT

Endoscopic Mucosal Resection Versus Endoscopic Submucosal Dissection for Colorectal Laterally Spreading Lesions.

Posted: October 20th, 2020, 2:00am GMT

Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers

Posted: July 7th, 2020, 2:00am GMT

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

Optimal Methods of Disease Progression and Survival Analysis in Children and Adults Patients With Adrenocortical Cancer (ACC)

Posted: April 22nd, 2020, 2:00am GMT

Conditions: Adrenocortical Carcinoma
Sponsors: National Cancer Institute (NCI)
Active, not recruiting

Permalink for 'Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial'

Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial

Posted: February 26th, 2020, 3:00am GMT

Conditions: Malignant Solid Neoplasm; Recurrent Adrenal Gland Pheochromocytoma; Recurrent Ectomesenchymoma; Recurrent Ependymoma; Recurrent Ewing Sarcoma; Recurrent Hepatoblastoma; Recurrent Kidney Wilms Tumor; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Medulloblastoma; Recurrent Melanoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdoid Tumor of the Kidney; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Recurrent Thyroid Gland Carcinoma; Recurrent WHO Grade 2 Glioma; Refractory Adrenal Gland Pheochromocytoma; Refractory Ependymoma; Refractory Ewing Sarcoma; Refractory Hepatoblastoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Medulloblastoma; Refractory Melanoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Rhabdoid Tumor of the Kidney; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma; Refractory Thyroid Gland Carcinoma; Refractory WHO Grade 2 Glioma
Interventions: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration and Biopsy; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Procedure: Radionuclide Imaging; Drug: Tipifarnib
Sponsors: National Cancer Institute (NCI)
Recruiting

Stereotactic Magnetic Resonance Guided Radiation Therapy

Posted: October 3rd, 2019, 2:00am GMT

The Registry of Oncology Outcomes Associated With Testing and Treatment

Posted: July 22nd, 2019, 2:00am GMT

A Study of E7386 in Participants With Advanced Solid Tumor Including Colorectal Cancer (CRC)

Posted: February 7th, 2019, 3:00pm GMT

Conditions: Solid Neoplasms; Colorectal Neoplasms; Gastrointestinal Tumors
Interventions: Drug: E7386
Sponsors: Eisai Co., Ltd.
Recruiting

A Phase 1/2 Study of [225Ac]-FPI-1434 Injection

Posted: November 19th, 2018, 3:00pm GMT

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

Extension Study to Evaluate the Safety of Long-Term Use of Relacorilant in Patients With Cushing Syndrome

Posted: July 27th, 2018, 2:00am GMT

Conditions: Cushing Syndrome
Interventions: Drug: relacorilant
Sponsors: Corcept Therapeutics
Enrolling by invitation

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, 2:00pm GMT

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)
Recruiting

Cabozantinib in Treating Patients With Locally Advanced or Metastatic Unresectable Adrenocortical Carcinoma

Posted: December 12th, 2017, 3:00am GMT

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
Active, not recruiting

Feasibility and Safety of IMP321 (Eftilagimod Alpha) for Advanced Stage Solid Tumors

Posted: August 17th, 2017, 2:00am GMT

Conditions: Solid Tumors; Peritoneal Carcinomatosis
Interventions: Drug: IMP321; Drug: Avelumab
Sponsors: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Recruiting

Surgery and Heated Intraperitoneal Chemotherapy for Adrenocortical Carcinoma

Posted: April 25th, 2017, 2:00pm GMT

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, 3:00pm GMT

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
Intervention:
Sponsor: St. Jude Children's Research Hospital
Recruiting

Pembrolizumab in Treating Patients With Rare Tumors That Cannot Be Removed by Surgery or Are Metastatic

Posted: March 29th, 2016, 2:00am GMT

Conditions: Advanced Malignant Solid Neoplasm; Carcinoma of Unknown Primary; Metastatic Adrenal Gland Pheochromocytoma; Metastatic Kidney Medullary Carcinoma; Metastatic Malignant Germ Cell Tumor; Metastatic Malignant Solid Neoplasm; Metastatic Paraganglioma; Metastatic Penile Carcinoma; Metastatic Skin Squamous Cell Carcinoma; Small Cell Carcinoma; Stage III Adrenal Cortex Carcinoma AJCC v7; Stage IV Adrenal Cortex Carcinoma AJCC v7; Stage IV Penile Cancer AJCC v7; Stage IV Renal Cell Cancer AJCC v7; Unresectable Adrenal Gland Pheochromocytoma; Unresectable Paraganglioma; Unresectable Skin Squamous Cell Carcinoma; Unresectable Solid Neoplasm; Vascular Neoplasm
Interventions: Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Other: Questionnaire Administration
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
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, 2:00am GMT

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)
Active, not recruiting

$Permalink for 'Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)'$

Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)

Posted: June 8th, 2015, 2:00am GMT

Conditions: Advanced Malignant Solid Neoplasm; Bladder Carcinoma; Breast Carcinoma; Cervical Carcinoma; Colon Carcinoma; Colorectal Carcinoma; Endometrial Carcinoma; Esophageal Carcinoma; Gastric Carcinoma; Glioma; Head and Neck Carcinoma; Kidney Carcinoma; Liver and Intrahepatic Bile Duct Carcinoma; Lung Carcinoma; Lymphoma; Malignant Uterine Neoplasm; Melanoma; Multiple Myeloma; Ovarian Carcinoma; Pancreatic Carcinoma; Prostate Carcinoma; Rectal Carcinoma; Recurrent Bladder Carcinoma; Recurrent Breast Carcinoma; Recurrent Cervical Carcinoma; Recurrent Colon Carcinoma; Recurrent Colorectal Carcinoma; Recurrent Esophageal Carcinoma; Recurrent Gastric Carcinoma; Recurrent Glioma; Recurrent Head and Neck Carcinoma; Recurrent Liver Carcinoma; Recurrent Lung Carcinoma; Recurrent Lymphoma; Recurrent Malignant Solid Neoplasm; Recurrent Melanoma; Recurrent Multiple Myeloma; Recurrent Ovarian Carcinoma; Recurrent Pancreatic Carcinoma; Recurrent Prostate Carcinoma; Recurrent Rectal Carcinoma; Recurrent Skin Carcinoma; Recurrent Thyroid Gland Carcinoma; Recurrent Uterine Corpus Cancer; Refractory Lymphoma; Refractory Malignant Solid Neoplasm; Refractory Multiple Myeloma; Skin Carcinoma; Thyroid Gland Carcinoma; Uterine Corpus Cancer
Interventions: Drug: Adavosertib; Drug: Afatinib; Drug: Afatinib Dimaleate; Drug: Binimetinib; Procedure: Biopsy; Procedure: Biospecimen Collection; Drug: Capivasertib; Procedure: Computed Tomography; Drug: Copanlisib; Drug: Copanlisib Hydrochloride; Drug: Crizotinib; Other: Cytology Specimen Collection Procedure; Drug: Dabrafenib; Drug: Dabrafenib Mesylate; Drug: Dasatinib; Drug: Defactinib; Drug: Defactinib Hydrochloride; Procedure: Echocardiography; Drug: Erdafitinib; Drug: FGFR Inhibitor AZD4547; Drug: Ipatasertib; Other: Laboratory Biomarker Analysis; Drug: Larotrectinib; Drug: Larotrectinib Sulfate; Procedure: Magnetic Resonance Imaging; Biological: Nivolumab; Drug: Osimertinib; Drug: Palbociclib; Biological: Pertuzumab; Drug: PI3K-beta Inhibitor GSK2636771; Procedure: Radiologic Examination; Biological: Relatlimab; Drug: Sapanisertib; Drug: Sunitinib Malate; Drug: Taselisib; Drug: Trametinib; Biological: Trastuzumab; Biological: Trastuzumab Emtansine; Drug: Ulixertinib; Drug: Vismodegib
Sponsors: National Cancer Institute (NCI)
Active, not recruiting

Prospective Observational Analysis Of CR With Sunitinib Treatment In mRCC Patients

Posted: September 4th, 2013, 2:00am GMT

Conditions: Complete Remission in Renal Cell Carcinoma
Interventions: Drug: sunitinib; Drug: sunitinib
Sponsors: Pfizer
Completed

European Low and Intermediate Risk Neuroblastoma Protocol

Posted: November 16th, 2012, 3:00am GMT

Conditions: LOW AND INTERMEDIATE PAEDIATRIC NEUROBLASTOMA AND NEONATAL SUPRARENAL MASSES
Interventions: Drug: chemotherapy
Sponsors: Instituto de Investigacion Sanitaria La Fe
Completed

Natural History Study of Children and Adults With Medullary Thyroid Cancer

Posted: August 9th, 2012, 2:00am GMT

Conditions: Medullary Thyroid Cancer
Sponsors: National Cancer Institute (NCI)
Recruiting

Paclitaxel, Cyclophosphamide & Doxorubicin, Autologous Dendritic Cells & Surgery in Stage II/III Breast Cancer (Women)

Posted: July 11th, 2007, 2:00am GMT

Conditions: Breast Cancer
Interventions: Biological: therapeutic autologous dendritic cells; Drug: aromatase inhibition therapy; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: paclitaxel; Drug: tamoxifen citrate; Genetic: gene expression analysis; Genetic: protein expression analysis; Genetic: reverse transcriptase-polymerase chain reaction; Other: immunoenzyme technique; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis; Procedure: adjuvant therapy; Procedure: biopsy; Procedure: conventional surgery; Procedure: neoadjuvant therapy; Radiation: radiation therapy
Sponsors: University of Nebraska; National Cancer Institute (NCI)
Completed

Cisplatin-Based Chemotherapy and/or Surgery in Treating Young Patients With Adrenocortical Tumor

Posted: March 17th, 2006, 3:00am GMT

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

Laparoscopic surgery for adrenocortical carcinoma: Estimating the risk of margin-positive resection

Fetched: December 2nd, 2023, 5:00am GMT by Kendyl Carlisle

J Surg Oncol. 2023 Nov 30. doi: 10.1002/jso.27544. Online ahead of print.

ABSTRACT

PMID:38037311 | DOI:10.1002/jso.27544

Adrenocortical carcinoma - 12-year observation period in a single centre. Case report with literature review

Fetched: December 1st, 2023, 5:00am GMT by Patrycja Dasiewicz

Pediatr Endocrinol Diabetes Metab. 2023;29(3):202-208. doi: 10.5114/pedm.2023.132131.

ABSTRACT

PMID:38031835 | PMC:PMC10679906 | DOI:10.5114/pedm.2023.132131

Permalink for 'Machine learning combining multi-omics data and network algorithms identifies adrenocortical carcinoma prognostic biomarkers'

Machine learning combining multi-omics data and network algorithms identifies adrenocortical carcinoma prognostic biomarkers

Fetched: November 30th, 2023, 5:00am GMT by Roberto Martin-Hernandez

Front Mol Biosci. 2023 Nov 6;10:1258902. doi: 10.3389/fmolb.2023.1258902. eCollection 2023.

ABSTRACT

Background: Rare endocrine cancers such as Adrenocortical Carcinoma (ACC) present a serious diagnostic and prognostication challenge. The knowledge about ACC pathogenesis is incomplete, and patients have limited therapeutic options. Identification of molecular drivers and effective biomarkers is required for timely diagnosis of the disease and stratify patients to offer the most beneficial treatments. In this study we demonstrate how machine learning methods integrating multi-omics data, in combination with system biology tools, can contribute to the identification of new prognostic biomarkers for ACC. Methods: ACC gene expression and DNA methylation datasets were downloaded from the Xena Browser (GDC TCGA Adrenocortical Carcinoma cohort). A highly correlated multi-omics signature discriminating groups of samples was identified with the data integration analysis for biomarker discovery using latent components (DIABLO) method. Additional regulators of the identified signature were discovered using Clarivate CBDD (Computational Biology for Drug Discovery) network propagation and hidden nodes algorithms on a curated network of molecular interactions (MetaBase™). The discriminative power of the multi-omics signature and their regulators was delineated by training a random forest classifier using 55 samples, by employing a 10-fold cross validation with five iterations. The prognostic value of the identified biomarkers was further assessed on an external ACC dataset obtained from GEO (GSE49280) using the Kaplan-Meier estimator method. An optimal prognostic signature was finally derived using the stepwise Akaike Information Criterion (AIC) that allowed categorization of samples into high and low-risk groups. Results: A multi-omics signature including genes, micro RNA's and methylation sites was generated. Systems biology tools identified additional genes regulating the features included in the multi-omics signature. RNA-seq, miRNA-seq and DNA methylation sets of features revealed a high power to classify patients from stages I-II and stages III-IV, outperforming previously identified prognostic biomarkers. Using an independent dataset, associations of the genes included in the signature with Overall Survival (OS) data demonstrated that patients with differential expression levels of 8 genes and 4 micro RNA's showed a statistically significant decrease in OS. We also found an independent prognostic signature for ACC with potential use in clinical practice, combining 9-gene/micro RNA features, that successfully predicted high-risk ACC cancer patients. Conclusion: Machine learning and integrative analysis of multi-omics data, in combination with Clarivate CBDD systems biology tools, identified a set of biomarkers with high prognostic value for ACC disease. Multi-omics data is a promising resource for the identification of drivers and new prognostic biomarkers in rare diseases that could be used in clinical practice.

PMID:38028548 | PMC:PMC10658191 | DOI:10.3389/fmolb.2023.1258902

Robot-assisted adrenalectomy: Step-by-step technique and surgical outcomes at a high-volume robotic center

Fetched: November 30th, 2023, 5:00am GMT by Federico Piramide

Asian J Urol. 2023 Oct;10(4):475-481. doi: 10.1016/j.ajur.2023.04.001. Epub 2023 Jun 15.

ABSTRACT

OBJECTIVE: In the last years, robotic surgery was introduced in several different settings with good perioperative results. However, its role in the management of adrenal masses is still debated. In order to provide a contribution to this field, we described our step-by-step technique for robotic adrenalectomy (RA) and related modifications according to the type of adrenal mass treated.

METHODS: We retrospectively analyzed 27 consecutive patients who underwent RA at Onze-Lieve-Vrouw hospital (Aalst, Belgium) between January 2009 and October 2022. Demographic, intra- and post-operative, and pathological data were retrieved from our prospectively maintained institutional database. Continuous variables are summarized as median and interquartile range (IQR). Categorical variables are reported as frequencies (percentages).

RESULTS: Twenty-seven patients underwent RA were included in the study. Median age, body mass index, and Charlson's comorbidity index were 61 (IQR: 49-71) years, 26 (IQR: 24-29) kg/m², and 2 (IQR: 0-3), respectively, and 16 (59.3%) patients were male. Median tumor size at computed tomography scan was 6.0 (IQR: 3.5-8.0) cm. Median operative time and blood loss were 105 (IQR: 82-120) min and 175 (IQR: 94-250) mL, respectively. No intraoperative complications were recorded. Overall postoperative complications rate was 11.1%, with a postoperative transfusion rate of 3.7%. A total of 10 (37.0%) patients harbored malignant adrenal masses. Among them, 3 (11.1%) had adrenocortical carcinoma, 6 (22.2%) secondary metastasis, and 1 (3.7%) malignant pheochromocytoma on final pathological exam. Only 1 (10.0%) patient had positive surgical margins.

CONCLUSION: We described our step-by-step technique for RA, which can be safely performed even in case of high challenging settings as malignant tumors, pheochromocytoma, and large masses. The standardization of perioperative protocol should be encouraged to maximize the outcomes of this complex surgical procedure.

PMID:38024438 | PMC:PMC10659974 | DOI:10.1016/j.ajur.2023.04.001

Cushing Syndrome due to Adrenocortical Carcinoma During Pregnancy

Fetched: November 30th, 2023, 5:00am GMT by Jack Andrew Morris

JCEM Case Rep. 2023 Nov 16;1(6):luad118. doi: 10.1210/jcemcr/luad118. eCollection 2023 Nov.

ABSTRACT

Cushing syndrome resulting from adrenocortical carcinoma in pregnancy is exceedingly rare. There are no validated guidelines to establish a diagnosis or guide management in pregnancy. We provide a case of a 31-year-old woman presenting for management of diabetes in pregnancy who appeared cushingoid. She was subsequently diagnosed with ACTH-independent Cushing syndrome and experienced preterm labor at 33 weeks' gestation, delivering a healthy infant. Four weeks postpartum, the patient underwent a left adrenalectomy and was subsequently diagnosed with adrenocortical carcinoma.

PMID:38021076 | PMC:PMC10652247 | DOI:10.1210/jcemcr/luad118

APOBEC3C is a novel target for the immune treatment of lower-grade gliomas

Fetched: November 27th, 2023, 5:00am GMT by Shufa Zhao

Neurol Res. 2023 Nov 26:1-16. doi: 10.1080/01616412.2023.2287340. Online ahead of print.

ABSTRACT

BACKGROUND: Apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) type 3C (A3C) has been identified as a cancer molecular biomarker in the past decade. However, the practical role of A3C in lower-grade gliomas (LGGs) in improving the clinical outcome remains unclear. This study aims to discuss the function of A3C in immunotherapy in LGGs.

METHODS: The RNA-Sequencing (RNA-seq) and corresponding clinical data were extracted from UCSC Xena and the results were verified in the Chinese Glioma Genome Atlas (CGGA). Weighted gene co-expression network analysis (WGCNA) was used for screening A3C-related genes. Comprehensive bioinformation analyses were performed and multiple levels of expression, survival rate, and biological functions were assessed to explore the functions of A3C.

RESULTS: A3C expression was significantly higher in LGGs than in normal tissues but lower than in glioblastoma (GBM), indicating its role as an independent prognosis predictor for LGGs. Twenty-eight A3C-related genes were found with WGCNA for unsupervised clustering analysis and three modification patterns with different outcomes and immune cell infiltration were identified. A3C and the A3C score were also correlated with immune cell infiltration and the expression of immune checkpoints. In addition, the A3C score was correlated with increased sensitivity to chemotherapy. Single-cell RNA (scRNA) analysis indicated that A3C most probably expresses on immune cells, such as T cells, B cells and macrophage.

CONCLUSIONS: A3C is an immune-related prognostic biomarker in LGGs. Developing drugs to block A3C could enhance the efficiency of immunotherapy and improve disease survival.Abbreviation: A3C: Apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) type 3C; LGGs: lower-grade gliomas; CGGA: Chinese Glioma Genome Atlas; WGCNA: Weighted gene co-expression network analysis; scRNA: Single-cell RNA; HGG: higher-grade glioma; OS: overall survival; TME: tumor microenvironment; KM: Kaplan-Meier; PFI: progression-free interval; IDH: isocitrate dehydrogenase; ROC: receiver operating characteristic; GS: gene significance; MM: module membership; TIMER: Tumor IMmune Estimation Resource; GSVA: gene set variation analysis; ssGSEA: single-sample gene-set enrichment analysis; PCA: principal component analysis; AUC: area under ROC curve; HAVCR2: hepatitis A virus cellular receptor 2; PDCD1: programmed cell death 1; PDCD1LG2: PDCD1 ligand 2; PTPRC: protein tyrosine phosphatase receptor type C; ACC: Adrenocortical carcinoma; BLCA: Bladder Urothelial Carcinoma;BRCA: Breast invasive carcinoma; CESC: Cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOLCholangiocarcinoma; COADColon adenocarcinoma; DLBC: Lymphoid Neoplasm Diffuse Large B-cell Lymphoma; ESCA: Esophageal carcinoma; GBM: Glioblastoma multiforme; HNSC: Head and Neck squamous cell carcinoma; KICH: Kidney Chromophobe; KIRC: Kidney renal clear cell carcinoma; KIRP: Kidney renal papillary cell carcinoma; LAML: Acute Myeloid Leukemia; LGG: Brain Lower Grade Glioma; LIHC: Liver hepatocellular carcinoma; LUAD: Lung adenocarcinoma; LUSC: Lung squamous cell carcinoma; MESO: Mesothelioma; OV: Ovarian serous cystadenocarcinoma; PAAD: Pancreatic adenocarcinoma; PCPG: Pheochromocytoma and Paraganglioma; PRAD: Prostate adenocarcinoma; READ: Rectum adenocarcinoma; SARC: Sarcoma; SKCM: Skin Cutaneous Melanoma; STAD: Stomach adenocarcinoma; TGCT: Testicular Germ Cell Tumors; THCA: Thyroid carcinoma; THYM: Thymoma; UCEC: Uterine Corpus Endometrial Carcinoma; UCS: Uterine Carcinosarcoma; UVM: Uveal Melanoma.

PMID:38007705 | DOI:10.1080/01616412.2023.2287340

Permalink for 'An Asymptomatic, Ectopic Mass as a Presentation of Adrenocortical Carcinoma Due to a Novel Germline TP53 p.Phe338Leu Tetramerisation Domain Variant'

An Asymptomatic, Ectopic Mass as a Presentation of Adrenocortical Carcinoma Due to a Novel Germline TP53 p.Phe338Leu Tetramerisation Domain Variant

Fetched: November 26th, 2023, 5:00am GMT by Justyna Walenciak

Children (Basel). 2023 Nov 7;10(11):1793. doi: 10.3390/children10111793.

ABSTRACT

Adrenocortical carcinoma (ACC) is a rare cancer in childhood. ACC is frequently associated with germline TP53 variants, with founder effects especially due to the p.Arg337His mutation. ACC leads to the secretion of adrenocortical hormones, resulting in endocrine syndromes, which is the usual trigger for establishing the diagnosis. We present a surprising ACC pathology in a non-secreting, ectopic retroperitoneal tumour in a 4-year-old boy, successfully controlled with chemotherapy and mitotane after microscopically incomplete tumour resection with spillage. Genomic analysis (gene panel sequencing and copy-number microarray) demonstrated a novel p.Phe338Leu tetramerisation domain (TD) TP53 variant in the proband and his cancer-free mother and a monoallelic deletion encompassing the TP53 locus in cancer tissue, consistent with cancer-predisposition syndrome. While the recurrent p.Arg337His variant translates into high ACC risk, residue 338 and, in general, TD domain variants drive heterogeneous clinical scenarios, despite generally being considered less disruptive than TP53 DNA-binding domain mutations.

PMID:38002884 | PMC:PMC10670401 | DOI:10.3390/children10111793

Landscape of Adrenal Tumours in Patients with Congenital Adrenal Hyperplasia

Fetched: November 26th, 2023, 5:00am GMT by Mara Carsote

Biomedicines. 2023 Nov 16;11(11):3081. doi: 10.3390/biomedicines11113081.

ABSTRACT

Our aim is to update the topic of adrenal tumours (ATs) in congenital adrenal hyperplasia (CAH) based on a multidisciplinary, clinical perspective via an endocrine approach. This narrative review is based on a PubMed search of full-length, English articles between January 2014 and July 2023. We included 52 original papers: 9 studies, 8 case series, and 35 single case reports. Firstly, we introduce a case-based analysis of 59 CAH-ATs cases with four types of enzymatic defects (CYP21A2, CYP17A1, CYP17B1, and HSD3B2). Secondarily, we analysed prevalence studies; their sample size varied from 53 to 26,000 individuals. AT prevalence among CAH was of 13.3-20%. CAH prevalence among individuals with previous imaging diagnosis of AT was of 0.3-3.6%. Overall, this 10-year, sample-based analysis represents one of the most complex studies in the area of CAH-ATs so far. These masses should be taken into consideration. They may reach impressive sizes of up to 30-40 cm, with compressive effects. Adrenalectomy was chosen based on an individual multidisciplinary decision. Many tumours are detected in subjects with a poor disease control, or they represent the first step toward CAH identification. We noted a left lateralization with a less clear pathogenic explanation. The most frequent tumour remains myelolipoma. The risk of adrenocortical carcinoma should not be overlooked. Noting the increasing prevalence of adrenal incidentalomas, CAH testing might be indicated to identify non-classical forms of CAH.

PMID:38002081 | PMC:PMC10669095 | DOI:10.3390/biomedicines11113081

A novel cuproptosis-related prognostic gene signature in adrenocortical carcinoma

Fetched: November 25th, 2023, 5:00am GMT by Wenjun Gao

J Clin Lab Anal. 2023 Nov 23:e24981. doi: 10.1002/jcla.24981. Online ahead of print.

ABSTRACT

BACKGROUND: Adrenocortical carcinoma (ACC) is an aggressive and rare malignant tumor associated with poor outcomes. Cuproptosis, a new pattern of cell death, relies on mitochondrial respiration and is associated with protein lipoylation. Increasing evidence has demonstrated the potential roles of cuproptosis in several tumor entities. However, the relationship between cuproptosis and ACC remains unclear.

METHODS: In total, 10 cuproptosis-related genes (CRGs) of patients with ACC were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases and differential expression analysis of CRGs was analyzed. Functional enrichment of the CRGs was performed and protein-protein interaction analysis was utilized to explore the association between the CRGs. Cuproptosis-related risk score (CRRS) was constructed by Lasso Cox regression and validated.

RESULTS: In the current study, the alteration and expression patterns of 10 CRGs in TCGA-ACC datasets were analyzed. We identified different expression patterns of CRGs in ACCs, discovered strong associations between CRGs and ACCs, and found that the CRGs were associated with immune infiltration in ACCs. A CRRS was created thereafter to predict overall survival (OS). CRRS = (0.083103718) *FDX1 + (-0.278423862) *LIAS+(0.090985682) *DLAT+(-0.018784047) *PDHA1 + (0.297218951) *MTF1 + (0.310197964) *CDKN2A. Patients were divided into high- and low-risk groups based on their CRRS, and independent prognostic factors were investigated. Finally, CDKN2A and FDX1 were found to be independent prognostic predictors of patients with ACC.

CONCLUSIONS: CDKN2A and FDX1 are independent prognostic predictors of patients with ACC. Cuproptosis may play a role in the development of ACC, providing a new perspective on therapeutic strategies related to CRGs for cancer prevention and treatment.

PMID:37997497 | DOI:10.1002/jcla.24981

Primary adrenal diffuse large B cell Lymphoma with Tumor thrombus in central adrenal vein: a case report and literature review

Fetched: November 24th, 2023, 5:00am GMT by Qingfei Xing

BMC Endocr Disord. 2023 Nov 24;23(1):258. doi: 10.1186/s12902-023-01496-y.

ABSTRACT

PMID:37996831 | PMC:PMC10668467 | DOI:10.1186/s12902-023-01496-y

ASO Author Reflections: Surgical Decision-Making in Adrenocortical Carcinoma: When Less is More

Fetched: November 23rd, 2023, 5:00am GMT by Jesse E Passman

Ann Surg Oncol. 2023 Nov 22. doi: 10.1245/s10434-023-14630-w. Online ahead of print.

NO ABSTRACT

PMID:37993746 | DOI:10.1245/s10434-023-14630-w

PLK1 inhibitors as a new targeted treatment for adrenocortical carcinoma

Fetched: November 23rd, 2023, 5:00am GMT by Emily Warmington

Endocr Connect. 2023 Nov 1:EC-23-0403. doi: 10.1530/EC-23-0403. Online ahead of print.

ABSTRACT

Adrenocortical carcinoma (ACC) is an aggressive malignancy with limited treatment options. Polo-like kinase 1 (PLK1) is a promising drug target; PLK1 inhibitors (PLK1i) have been investigated in solid cancers and are more effective in TP53-mutated cases. We evaluated PLK1 expression in ACC samples and the efficacy of two PLK1i in ACC cell lines with different genetic backgrounds. PLK1 protein expression was investigated by immunohistochemistry in tissue samples and correlated with clinical data. The efficacy of Rigosertib (RGS), targeting RAS/PI3K, CDKs and PLKs, and Poloxin (Pol), specifically targeting the PLK1 polo-box domain, was tested in TP53-mutated NCI-H295R, MUC-1, and CU-ACC2 cells and in TP53-wild-type CU-ACC1. Effects on proliferation, apoptosis and viability were determined. PLK1 immunostaining was stronger in TP53-mutated ACC samples vs wild-type (p=0.0017). High PLK1 expression together with TP53 mutations correlated with shorter progression-free survival (p=0.041). NCI-H295R showed a time- and dose-dependent reduction in proliferation with both PLK1i (p<0.05 at 100nM RGS and 30µM Pol). In MUC-1, a less pronounced decrease was observed (p<0.05 at 1000nM RGS and 100µM Pol). 100nM RGS increased apoptosis in NCI-H295R (p<0.001), with no effect on MUC-1. CU-ACC2 apoptosis was induced only at high concentrations (p<0.05 at 3000nM RGS and 100µM Pol), while proliferation decreased at 1000nM RGS and 30µM Pol. CU-ACC1 proliferation reduced, and apoptosis increased, only at 100µM Pol. TP53-mutated ACC cell lines demonstrated better response to PLK1i than wild-type CU-ACC1. These data suggest PLK1i may be a promising targeted treatment of a subset of ACC patients, pre-selected according to tumour genetic signature.

PMID:37992487 | DOI:10.1530/EC-23-0403

Hepatic Metastasectomy in Pediatric Patients: An Observational Study

Fetched: November 20th, 2023, 5:00am GMT by Andrew M Fleming

J Pediatr Surg. 2023 Oct 23:S0022-3468(23)00646-2. doi: 10.1016/j.jpedsurg.2023.10.036. Online ahead of print.

ABSTRACT

BACKGROUND: The role of hepatectomy for metastatic disease in children is controversial. Rationales include potential cure, obtaining a diagnosis, and guiding chemotherapy decisions. This study examines the safety and utility of hepatic metastasectomy for children at a single institution.

METHODS: After IRB approval (#22-1258), medical records were reviewed from 1995 to 2022 for children undergoing hepatic metastasectomy. En-bloc hepatectomies during primary tumor resection were excluded.

RESULTS: Hepatic metastasectomy was performed in 16 patients for a variety of histologies. Median patient age was 12.2 years [IQR 6.9-22.6], and 13/16 patients were female (81 %). Number of hepatic metastases ranged from 1 to 23 and involved between 1 and 8 Couinaud segments. Anatomic resections included 4 hemihepatectomies and 1 sectionectomy. All other resections were nonanatomic. 3/6 resections for germ cell tumor (GCT) revealed only mature teratoma, driving adjuvant therapy decisions. When indicated, median time to adjuvant chemotherapy was 19 days [IQR 11-22]. No patients had Clavien-Dindo Class III or higher perioperative morbidity. Three patients (1 GCT, 1 adrenocortical carcinoma (ACC), and 1 gastric neuroendocrine tumor (GNET) experienced hepatic relapse. The patients with relapsed GCT and GNET are alive with disease at 17 and 135 months, respectively. The patient with ACC died of disease progression and liver failure. One patient with Wilms tumor experienced extrahepatic, retroperitoneal recurrence and died. With a median follow-up of 38 months, 10-year disease-specific and disease-free survival were 77 % and 61 %, respectively.

CONCLUSIONS: Hepatic metastasectomy can be accomplished safely in children, may guide adjuvant therapy decisions, and is associated with long-term survival in selected patients.

LEVEL OF EVIDENCE: Level IV.

TYPE OF STUDY: Treatment Study, Case series with no comparison group.

PMID:37980196 | DOI:10.1016/j.jpedsurg.2023.10.036

ASO Visual Abstract: Defining Optimal Management of Nonmetastatic Adrenocortical Carcinoma

Fetched: November 19th, 2023, 5:00am GMT by Jesse E Passman

Ann Surg Oncol. 2023 Nov 17. doi: 10.1245/s10434-023-14615-9. Online ahead of print.

NO ABSTRACT

PMID:37978113 | DOI:10.1245/s10434-023-14615-9

Impact of EDP-M on survival of patients with metastatic adrenocortical carcinoma: A population-based study

Fetched: November 19th, 2023, 5:00am GMT by Pien Debets

Eur J Cancer. 2023 Nov 10;196:113424. doi: 10.1016/j.ejca.2023.113424. Online ahead of print.

ABSTRACT

INTRODUCTION: Historically, stage IV adrenocortical carcinoma (mACC) has a poor prognosis with a median overall survival (OS) of only 5 months. Based on the FIRM-ACT trial published in 2012, guidelines now advise first line systemic treatment with etoposide, cisplatin, doxorubicin and mitotane (EDP-M). The effect of EDP-M on patient survival in clinical practice in the Netherlands is unknown.

METHODS: The data of all patients with mACC (2005-2020) were obtained from the Netherlands comprehensive cancer organization (IKNL). The effect of EDP-M on patient survival was assessed using Kaplan-Meier analysis and multivariate Cox regression analysis including clinical, therapy and tumor characteristics.

RESULTS: In total 167 patients with mACC were included. For patients diagnosed from 2014 onwards, EDP-M (in 22 patients (22%)) lead to a numerically but not statistically significant improved OS compared to those not receiving EDP-M (11.8 vs 5.6 months, p = 0.525). For systemic treatments, patients treated with mitotane only had the best 5-year OS (11.4%, p = 0.006) regardless of year of diagnosis. In multivariate Cox regression analysis EPD-M was not associated with OS; palliative adrenalectomy (HR: 0.26, p = <.001) and local treatment of metastases (HR: 0.35, p = 0.001) were associated with a better OS and a primary tumor Ki-67 index > 20% (HR: 2.67, p = 0.003) with a worse OS from 2014 onwards. Patients diagnosed before 2014 had a significantly poorer OS compared to from 2014 onwards (5-yr: 4.5 vs 8.4%, OS: 6.8 vs 8.3 months, p = 0.032).

CONCLUSION: OS for mACC in the Netherlands has improved in the last decade. Receiving EDP-M did not significantly improve OS for patients with mACC. The use of multimodality treatment including palliative adrenalectomy, mitotane and local treatment of (oligo-)metastases in appropriately selected patients has improved the OS for mACC patients since 2014.

PMID:37977106 | DOI:10.1016/j.ejca.2023.113424

Contrast CT radiomic features add value to prediction of prognosis in adrenal cortical carcinoma

Fetched: November 17th, 2023, 5:00am GMT by Jiacheng Liu

Endocrine. 2023 Nov 15. doi: 10.1007/s12020-023-03568-4. Online ahead of print.

ABSTRACT

OBJECTIVE: Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with poor prognosis due to high postoperative recurrence rates. The aim of this study is to develop a contrast CT radiomic feature-based prognosis prediction model for ACC and evaluate its performance by comparison with ENSAT staging system and S-GRAS score.

METHODS: Included in this study were 39 ACC patients, from which we extracted 1411 radiomic features. Using cross-validated least absolute shrinkage and selection operator regression (cv-LASSO regression), we generated a radiomic index. Additionally, we further validated the radiomic index using both univariate and multivariate Cox regression analyses. We constructed a radiomic nomogram that incorporated the radiomic signature and compared it with ENSAT stage and S-GRAS score in terms of calibration, discrimination and clinical usefulnes.

RESULTS: In this study, the average progression free survival (PFS) of 39 patients was 20.4 (IQR 9.1-60.1) months and the average overall survival (OS) was 57.8 (IQR 32.4-NA). The generated radiomic features were significantly associated with PFS, OS, independent of clinical-pathologic risk factors (HR 0.16, 95%CI 0.02-0.99, p = 0.05; HR 0.20, 95%CI 0.04-1.07, p = 0.06, respectively). The radiomic index, ENSAT stage, resection status, and Ki67% index incorporated nomogram exhibited better performance for both PFS and OS prediction as compared with the S-GRAS and ENSAT nomogram (C-index: 0.75 vs. C-index: 0.68, p = 0.030 and 0.67, p = 0.025; C-index: 0.78 vs. C-index: 0.72, p = 0.003 and 0.73, p = 0.006). Calibration curve analysis showed that the radiomics-based model performs best in predicting the two-year PFS and the three-year OS. Decision curve analysis demonstrated that the radiomic index nomogram outperformed the S-GRAS and ENSAT nomogram in predicting the two-year PFS and the three-year OS.

CONCLUSION: The contrast CT radiomic-based nomogram performed better than S-GRAS or ENSAT in predicting PFS and OS in ACC patients.

PMID:37968537 | DOI:10.1007/s12020-023-03568-4

Prognosis of Adrenal Oncocytic Neoplasms (AONs): Literature Review of 287 Cases and Presentation of the Oldest Patient

Fetched: November 15th, 2023, 5:00am GMT by Enrico Coppola Bottazzi

J Clin Med. 2023 Nov 4;12(21):6925. doi: 10.3390/jcm12216925.

ABSTRACT

METHODS: A comprehensive literature review using as key words "adrenal oncocytoma", "adrenal oncocytic neoplasm", and "adrenal oncocytic carcinoma" was performed.

PMID:37959390 | PMC:PMC10649738 | DOI:10.3390/jcm12216925

Validated predictive model for treatment and prognosis of adrenocortical carcinoma

Fetched: November 13th, 2023, 5:00am GMT by Samuel M Zuber

Surgery. 2023 Nov 10:S0039-6060(23)00618-9. doi: 10.1016/j.surg.2023.08.047. Online ahead of print.

ABSTRACT

BACKGROUND: Adrenocortical carcinoma has a poor prognosis and multiple clinical, pathological, and treatment variables. Currently, we lack a prognostic and treatment calculator to determine the survival and efficacy of adjuvant chemoradiation. We aimed to validate a calculator to assess prognosis and treatment.

METHODS: We searched the National Cancer Database to identify patients with adrenocortical carcinoma surgically treated from 2004 to 2020 and randomly allocated them into a training (80%) or validation set (20%). We analyzed the variables of age; sex; Charlson Comorbidity Index; insurance status; tumor size; pathologic tumor, node, and metastasis categories; surgical margins; and use of chemotherapy and radiation therapy. We used Cox regression prediction models and bootstrap coefficients to generate a mathematical model to predict 5- and 10-year overall survival. After using the area under the curve analysis to assess the model's performance, we compared overall survival in the training and validation sets.

RESULTS: Multivariable analysis of the 3,480 patients included in the study revealed that all variables were significant except sex (P < .05) and incorporated into a mathematical model. The area under the curve for 5- and 10-year overall survival was 0.68 and 0.70, respectively, for the training set and 0.70 and 0.72, respectively, for the validation set. For the bootstrap coefficients, the 5- and 10-year overall survival was 6.4% and 4.1%, respectively, above the observed mean.

CONCLUSION: Our model predicts the overall survival of patients with adrenocortical carcinoma based on clinical, pathologic, and treatment variables and can assist in individualizing treatment.

PMID:37953139 | DOI:10.1016/j.surg.2023.08.047

Permalink for 'CDK6 is a novel predictive and prognosis biomarker correlated with immune infiltrates in multiple human neoplasms, including small cell lung carcinoma'

CDK6 is a novel predictive and prognosis biomarker correlated with immune infiltrates in multiple human neoplasms, including small cell lung carcinoma

Fetched: November 12th, 2023, 5:00am GMT by Guo-Sheng Li

Funct Integr Genomics. 2023 Nov 10;23(4):332. doi: 10.1007/s10142-023-01253-3.

ABSTRACT

The roles of cyclin-dependent kinase 6 (CDK6) in various cancers, including small cell lung carcinoma (SCLC), remain unclear. Here, 111,54 multi-center samples were investigated to determine the expression, clinical significance, and underlying mechanisms of CDK6 in 34 cancers. The area under the curve (AUC), Cox regression analysis, and the Kaplan-Meier curves were used to explore the clinical value of CDK6 in cancers. Gene set enrichment analysis and correlation analysis were performed to detect potential CDK6 mechanisms. CDK6 expression was essential in 24 cancer cell types. Abnormal CDK6 expression was observed in 14 cancer types (e.g., downregulated in breast invasive carcinoma; p < 0.05). CDK6 allowed six cancers to be distinguished from their controls (AUC > 0.750). CDK6 expression was a prognosis marker for 13 cancers (e.g., adrenocortical carcinoma; p < 0.05). CDK6 was correlated with several immune-related signaling pathways and the infiltration levels of certain immune cells (e.g., CD8⁺ T cells; p < 0.05). Downregulated CDK6 mRNA and protein levels were observed in SCLC (p < 0.05, SMD = - 0.90). CDK6 allowed the identification of SCLC status (AUC = 0.91) and predicted a favorable prognosis for SCLC patients (p < 0.05). CDK6 may be a novel biomarker for the prediction and prognosis of several cancers, including SCLC.

PMID:37950078 | DOI:10.1007/s10142-023-01253-3

The effect of hormonal secretion on survival in adrenocortical carcinoma: A multi-center study

Fetched: November 10th, 2023, 5:00am GMT by Alaa Sada

Surgery. 2023 Nov 8:S0039-6060(23)00679-7. doi: 10.1016/j.surg.2023.04.070. Online ahead of print.

ABSTRACT

PMID:37945477 | DOI:10.1016/j.surg.2023.04.070

Durable response to pembrolizumab in microsatellite instability-high advanced adrenocortical carcinoma

Fetched: November 7th, 2023, 5:00am GMT by Masaya Senda

IJU Case Rep. 2023 Sep 21;6(6):382-385. doi: 10.1002/iju5.12628. eCollection 2023 Nov.

ABSTRACT

INTRODUCTION: Advanced adrenocortical carcinoma has a poor prognosis and is treated with chemotherapy that includes mitotane with etoposide, doxorubicin, and cisplatin as first-line therapy. However, second-line therapy has not been determined yet. Pembrolizumab has been approved for high microsatellite instability for which standard treatments have failed.

CASE PRESENTATION: Here, we present a patient with advanced adrenocortical carcinoma treated with complete surgical resection. 21 months later, he had local and metastatic recurrences. After four cycles of first-line therapy, we switched to pembrolizumab because microsatellite instability-high was detected in his tumor. He has received mitotane and pembrolizumab for 15 months, and this has exerted a radiographical response without severe adverse events.

CONCLUSION: We presented a patient with microsatellite instability-high advanced adrenocortical carcinoma treated with pembrolizumab and mitotane.

PMID:37928286 | PMC:PMC10622203 | DOI:10.1002/iju5.12628

Defining Optimal Management of Non-metastatic Adrenocortical Carcinoma

Fetched: November 6th, 2023, 5:00am GMT by Jesse E Passman

Ann Surg Oncol. 2023 Nov 5. doi: 10.1245/s10434-023-14533-w. Online ahead of print.

ABSTRACT

BACKGROUND: Adrenocortical carcinoma (ACC) is an aggressive, deadly malignancy. Resection remains the primary treatment; however, there is conflicting evidence regarding the optimal approach to and extent of surgery and the role of adjuvant therapy. We evaluated the impact of surgical technique and adjuvant therapies on survival in non-metastatic ACC.

METHODS: We performed a retrospective cohort study of subjects who underwent surgery for non-metastatic ACC between 2010 and 2019 utilizing the National Cancer Database. The primary outcome was overall survival. Cox proportional hazards models were developed to identify associations between clinical and treatment characteristics and survival.

RESULTS: Overall, 1175 subjects were included. Their mean age was 54 ± 15 years, and 62% of patients were female. 67% of procedures were performed via the open approach, 22% involved multi-organ resection, and 26% included lymphadenectomy. Median survival was 77.1 months. Age (hazard ratio [HR] 1.019; p < 0.001), advanced stage (stage III HR 2.421; p < 0.001), laparoscopic approach (HR 1.329; p = 0.010), and positive margins (HR 1.587; p < 0.001) were negatively associated with survival, while extent of resection (HR 1.189; p = 0.140) and lymphadenectomy (HR 1.039; p = 0.759) had no association. Stratified by stage, laparoscopic resection was only associated with worse survival in stage III disease (HR 1.548; p = 0.007). Chemoradiation was only associated with improved survival in patients with positive resection margins (HR 0.475; p = 0.004).

CONCLUSION: Tumor biology and surgical margins are the primary determinants of survival in non-metastatic ACC. Surgical extent and lymphadenectomy are not associated with overall survival. In advanced disease, the open approach is associated with improved survival.

PMID:37925657 | DOI:10.1245/s10434-023-14533-w

Permalink for 'Exploring the role of the disulfidptosis-related gene SLC7A11 in adrenocortical carcinoma: implications for prognosis, immune infiltration, and therapeutic strategies'

Exploring the role of the disulfidptosis-related gene SLC7A11 in adrenocortical carcinoma: implications for prognosis, immune infiltration, and therapeutic strategies

Fetched: November 4th, 2023, 5:00am GMT by Tonghu Liu

Cancer Cell Int. 2023 Nov 2;23(1):259. doi: 10.1186/s12935-023-03091-6.

ABSTRACT

BACKGROUND: Disulfidptosis and the disulfidptosis-related gene SLC7A11 have recently attracted significant attention for their role in tumorigenesis and tumour management. However, its association with adrenocortical carcinoma (ACC) is rarely discussed.

METHODS: Differential analysis, Cox regression analysis, and survival analysis were used to screen for the hub gene SLC7A11 in the TCGA and GTEx databases and disulfidptosis-related gene sets. Then, we performed an association analysis between SLC7A11 and clinically relevant factors in ACC patients. Univariate and multivariate Cox regression analyses were performed to evaluate the prognostic value of SLC7A11 and clinically relevant factors. Weighted gene coexpression analysis was used to find genes associated with SLC7A11. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and the LinkedOmics database were used to analyse the functions of SLC7A11-associated genes. The CIBERSORT and Xcell algorithms were used to analyse the relationship between SLC7A11 and immune cell infiltration in ACC. The TISIDB database was applied to search for the correlation between SLC7A11 expression and immune chemokines. In addition, we performed a correlation analysis for SLC7A11 expression and tumour mutational burden and immune checkpoint-related genes and assessed drug sensitivity based on SLC7A11 expression. Immunohistochemistry and RT‒qPCR were used to validate the upregulation of SLC7A11 in the ACC.

RESULTS: SLC7A11 is highly expressed in multiple urological tumours, including ACC. SLC7A11 expression is strongly associated with clinically relevant factors (M-stage and MYL6 expression) in ACC. SLC7A11 and the constructed nomogram can accurately predict ACC patient outcomes. The functions of SLC7A11 and its closely related genes are tightly associated with the occurrence of disulfidptosis in ACC. SLC7A11 expression was tightly associated with various immune cell infiltration disorders in the ACC tumour microenvironment (TME). It was positively correlated with the expression of immune chemokines (CXCL8, CXCL3, and CCL20) and negatively correlated with the expression of immune chemokines (CXCL17 and CCL14). SLC7A11 expression was positively associated with the expression of immune checkpoint genes (NRP1, TNFSF4, TNFRSF9, and CD276) and tumour mutation burden. The expression level of SLC7A11 in ACC patients is closely associated withcthe drug sensitivity.

CONCLUSION: In ACC, high expression of SLC7A11 is associated with migration, invasion, drug sensitivity, immune infiltration disorders, and poor prognosis, and its induction of disulfidptosis is a promising target for the treatment of ACC.

PMID:37919768 | PMC:PMC10623781 | DOI:10.1186/s12935-023-03091-6

Retroperitoneal Solid Pseudopapillary Tumor Mimicking Adrenal Malignant Tumor in a 67-Year-Old Man

Fetched: November 2nd, 2023, 5:00am GMT by Takahiro Ishii

JCEM Case Rep. 2023 Aug 14;1(4):luad090. doi: 10.1210/jcemcr/luad090. eCollection 2023 Jul.

ABSTRACT

Solid pseudopapillary tumor (SPT) is a low-grade malignant tumor of the pancreas. SPT typically affects women and can occur in ectopic pancreatic region; however, it also occurs rarely in retroperitoneum. The tumor may be bulky at the time of diagnosis since there is no specific clinical manifestation. Here we present an older male case with retroperitoneal SPT. A 67-year-old man consulted for intermittent fever and lumbago. His basal hormonal profile screened out a functional tumor. Computed tomography (CT) showed a gigantic mass in his left adrenal region. A normal left adrenal gland was not identified, and the tumor's feeding artery was recognized as the left adrenal artery by the contrast-enhanced CT. Adrenal malignant tumor was suspected, and tumor resection was performed. The resected tumor size was 15 × 10 × 9 cm. Histologically, epithelial-like cells with round nuclei and a small amount of eosinophilic cytoplasm proliferated in papillary (around the blood vessels) or uniformly solid form. By immunostaining, tumor cells were vimentin, CD56, cytokeratin AE1/AE3, CD10, β-catenin in the nucleus, cyclin D1, and PgR positive. These findings led to the diagnosis of SPT. Although rare, SPT should be considered as a differential diagnosis in cases of a mass arising from the adrenal region.

PMID:37908992 | PMC:PMC10580579 | DOI:10.1210/jcemcr/luad090

Two Cases of Adrenal Malignancy With Macroscopic Fat

Fetched: November 2nd, 2023, 5:00am GMT by Tom Wilkinson

JCEM Case Rep. 2023 Feb 7;1(1):luac029. doi: 10.1210/jcemcr/luac029. eCollection 2023 Jan.

ABSTRACT

The presence of macroscopic fat on computed tomography (CT) imaging has been traditionally regarded as an indication that an adrenal lesion is likely to be a benign myelolipoma, for which further investigation is not usually required. Two cases are described where an adrenal lesion was eventually found to be malignant on histology (adrenocortical carcinoma in the first case, undifferentiated sarcoma in the second case), despite the presence of macroscopic fat on CT. In both cases there were other clinical and radiological indicators of potential malignant pathology. These cases add to increasing awareness in the literature that malignant adrenal tumors may rarely contain macroscopic fat, emphasizing a need for clinical vigilance.

PMID:37908270 | PMC:PMC10578380 | DOI:10.1210/jcemcr/luac029

Metastatic Merkel Cell Carcinoma Within a Cortisol-producing Adrenal Adenoma

Fetched: November 2nd, 2023, 5:00am GMT by Lauren Cutrone

JCEM Case Rep. 2023 Sep 20;1(5):luad100. doi: 10.1210/jcemcr/luad100. eCollection 2023 Sep.

ABSTRACT

A 54-year-old man with hypertension, type 2 diabetes mellitus, and a history of Merkel cell carcinoma (MCC) of the right thigh presented to the emergency department with a 4-day history of right lower-quadrant abdominal pain associated with constipation and decreased appetite. Workup showed a heterogenous 6-cm right adrenal mass with macroscopic fat. Imaging was suggestive of benign pathology. Hormonal workup for the adrenal nodule led to the diagnosis of Cushing syndrome. The patient underwent a right adrenalectomy for Cushing syndrome with pathology revealing a 6.5-cm adrenocortical adenoma harboring a 2-cm, well-circumscribed neuroendocrine tumor consistent with metastatic MCC. Adrenal collision tumors are exceedingly rare. This case describes a collision tumor that has not previously been identified-a cortisol-producing adrenal adenoma and metastatic MCC.

PMID:37908218 | PMC:PMC10580440 | DOI:10.1210/jcemcr/luad100

Correction for: ASXL1 promotes adrenocortical carcinoma and is associated with chemoresistance to EDP regimen

Fetched: November 1st, 2023, 5:00am GMT by Liang Wang

Aging (Albany NY). 2023 Oct 30;15(20):11690-11691. doi: 10.18632/aging.205255. Epub 2023 Oct 30.

NO ABSTRACT

PMID:37906268 | PMC:PMC10637814 | DOI:10.18632/aging.205255

Giant adrenocortical carcinoma with androgen-producing causing male characteristics

Fetched: October 31st, 2023, 5:00am GMT by Changyi Jiang

Asian J Surg. 2023 Oct 28:S1015-9584(23)01617-2. doi: 10.1016/j.asjsur.2023.10.005. Online ahead of print.

NO ABSTRACT

PMID:37903692 | DOI:10.1016/j.asjsur.2023.10.005

Identification of Molecular Subtypes and Prognostic Characteristics of Adrenocortical Carcinoma Based on Unsupervised Clustering

Fetched: October 29th, 2023, 5:00am GMT by Yuan Zhang

Int J Mol Sci. 2023 Oct 23;24(20):15465. doi: 10.3390/ijms242015465.

ABSTRACT

PMID:37895143 | PMC:PMC10607826 | DOI:10.3390/ijms242015465

Adrenal Mass Biopsy in Patients Without Extra-Adrenal Primary Malignancy: A Multicenter Study

Fetched: October 26th, 2023, 5:00am GMT by Satheesh Krishna

AJR Am J Roentgenol. 2023 Oct 25. doi: 10.2214/AJR.23.29826. Online ahead of print.

ABSTRACT

Background: Adrenal washout CT is not useful for evaluating incidental adrenal masses in patients without known or suspected primary extra-adrenal malignancy. Objectives: To evaluate the diagnostic utility of adrenal mass biopsy (AMB) in patients without known or suspected extra-adrenal primary malignancy. Methods: This retrospective six-center study included 69 patients (mean age 56 years; 32 men, 37 women) without known or suspected extra-adrenal primary malignancy who underwent image-guided core-needle biopsy between January 2004 and June 2021 of a mass suspected to be arising from the adrenal gland. Biopsy results were classified as diagnostic or non-diagnostic. For masses resected after biopsy, histopathologic concordance was assessed between diagnoses from biopsy and resection. Masses were classified as benign or malignant by resection or imaging follow-up, classifying all nondiagnostic biopsies as false results. Results: Median mass size was 7.4 cm (range, 1.9-19.2 cm). AMB had diagnostic yield of 64% (44/69; 95% CI: 51%, 75%). After biopsy, 25 masses were resected, and 44 had imaging follow-up. Of masses that were resected after diagnostic biopsy, diagnosis was concordant between biopsy and resection in 100% (12/12). Of 13 masses that were resected after non-diagnostic biopsy, the diagnosis from resection was benign in 8 masses and malignant in 5 masses. The 44 masses with imaging follow-up included one mass with diagnostic biopsy yielding benign adenoma and two masses with non-diagnostic biopsy result that were all classified as malignant by imaging follow-up. Biopsy had overall sensitivity and specificity for malignancy of 73% (22/30) and 54% (21/39), respectively; diagnostic biopsies had sensitivity and specificity for malignancy of 96% (22/23) and 100% (21/21), respectively. Among nine nondiagnostic biopsies reported as adrenocortical neoplasm, six were classified as malignant by the reference standard (resection showing adrenal cortical carcinoma in 4, resection showing adrenocortical neoplasm of uncertain malignant potential in 1, malignant imaging follow-up in 1). Conclusion: AMB had low diagnostic yield, with low sensitivity and low specificity for malignancy. A biopsy result of adrenocortical neoplasm did not reliably differentiate benign and malignant adrenal masses. Clinical Impact: Biopsy appears to have limited utility for evaluation of incidental adrenal masses in patients without primary extra-adrenal malignancy.

PMID:37877600 | DOI:10.2214/AJR.23.29826

Exposure to anticancer drugs modulates the expression of ACSL4 and ABCG2 proteins in adrenocortical carcinoma cells

Fetched: October 24th, 2023, 5:00am GMT by Mayra Agustina Ríos Medrano

Heliyon. 2023 Oct 7;9(10):e20769. doi: 10.1016/j.heliyon.2023.e20769. eCollection 2023 Oct.

ABSTRACT

Adrenocortical carcinoma (ACC) is a rare and malignant disease, with more than 50 % of patients developing hormone-secreting tumors. These tumors are genetically heterogeneous and potentially lethal, as metastasis is often underway at the time of diagnosis. While chemoresistance can be multifactorial, Acyl CoA synthetase 4 (ACSL4) is known to contribute to the generation of highly aggressive cellular phenotypes, while increased expression and activity of multidrug transporters such as ATP-binding cassette subfamily G member 2 (ABCG2) are known to play a key role. Therefore, the objective of this work was to determine changes in the expression of ACSL4 and ABCG2 in ACC cell lines after exposure to antitumor drugs. Bioinformatics analysis of public database GSE140818 revealed higher ACSL4 and ABCG2 expression in HAC15 cells resistant to mitotane when compared to wild type cells. In addition, our studies revealed an increase in ACSL4 and ABCG2 expression in lowly aggressive H295R cells undergoing early treatment with non-lethal concentrations of mitotane, doxorubicin and cisplatin. Comparable results were obtained in lowly aggressive breast cancer cells MCF-7. The increase in ACSL4 and ABCG2 expression favored tumor cell viability, proliferation and compound efflux, an effect partially offset by ACSL4 and ABCG2 inhibitors. These results provide relevant data on the undesired molecular effects of antitumor drugs and may fuel future studies on patients' early response to antitumor treatment.

PMID:37867801 | PMC:PMC10585233 | DOI:10.1016/j.heliyon.2023.e20769

Li-Fraumeni Syndrome, A Rarity Among Rarities: A Case Report and Review of Literature

Fetched: October 21st, 2023, 5:00am GMT by Mariam Elremeli

Cureus. 2023 Sep 18;15(9):e45462. doi: 10.7759/cureus.45462. eCollection 2023 Sep.

ABSTRACT

Li-Fraumeni syndrome (LFS) is a rare inherited cancer susceptibility disorder with a wide tumour spectrum, particularly in children and young adults. Patients with LFS have life-long cancer risk, and the most commonly encountered tumours include soft tissue sarcoma, breast cancer, brain tumours, osteosarcoma, leukaemia and adrenocortical carcinoma. LFS is associated with mutations in the tumour suppressor gene TP53, andnearly two-thirds of families with LFS have this germline mutation. However, the diagnosis of LFS is currently based on recognised strict clinical criteria regardless of the genetic mutation status, as a few families with the clinical characteristics and cancer predisposition of LFS do not have TP53 mutations. Breast cancer is particularly significant among the common malignancies associated with LFS as it is the most common cancer in women worldwide. We present a case of a 27-year-old woman with unilateral breast cancer, in whom further history revealed a brain tumour at the age of 14 years. Due to the early onset of breast cancer and history of childhood malignancy, we suspected LFS. Genetic testing revealed a TP53 mutation, further suggesting the diagnosis of LFS. This has important implications in managing this patient's breast cancer, as the need for risk-reducing mastectomy and arranging a special surveillance programme. It also has great implications for the patient's family members, especially in terms of psychological impact, particularly when the mutation has been detected in children. Also, there is a need for periodic surveillance, which can help in early diagnosis and timely treatment with a more favourable outcome.

PMID:37859908 | PMC:PMC10583736 | DOI:10.7759/cureus.45462

Incidence and geographical distribution of adrenocortical carcinoma: Retrospective analysis of a state cancer registry

Fetched: October 21st, 2023, 5:00am GMT by Vania Balderrama-Brondani

Endocr Pract. 2023 Oct 18:S1530-891X(23)00588-8. doi: 10.1016/j.eprac.2023.10.004. Online ahead of print.

ABSTRACT

OBJECTIVE: Adrenocortical carcinoma (ACC) is a rare malignancy without established association with environmental risk factors. ACC incidence is stable based on large surgical databases while referral centers data reported increasing number of cases seen. We studied ACC incidence and distribution at a county level to find potential ACC "hot spots" that could be linked to environmental exposures.

METHODS: A retrospective analysis of Texas Cancer Registry that included ACC patients diagnosed between 2000 and 2018. County-level heatmaps were created and compared with breast, prostate, and lung cancer.

RESULTS: We identified 448 ACC cases during the study period. Cases were registered in 110 of the 254 counties (43.3%) in Texas, representing 92.74% of the total population. The median incidence was 23 new cases/y (range 14-33). The mean population-adjusted ACC incidence rate was 0.104 per 100 000 per year (standard deviation 0.005; 95% CI, 0.092-0.116). Seven counties (6.3%) accounted for 215 (48.0%) cases, with more than 10 cases each and median standardized incidence ratio (SIR) of 0.1 (range, 0.0-0.9). One hundred three counties (93.7%) accounted for the remaining 233 cases (52%), with fewer than 10 cases per county. The highest standardized incidence ratios were found in counties with a median population of fewer than 14 000 residents and with only one reported case.

CONCLUSION: Our analysis is the first report to create ACC heatmap and could not detect any geographic clustering of ACC in Texas. The incidence of ACC remained stable and consistent with data from other large databases.

PMID:37858722 | DOI:10.1016/j.eprac.2023.10.004

Advances in translational research of the rare cancer type adrenocortical carcinoma

Fetched: October 20th, 2023, 5:00am GMT by Chandrayee Ghosh

Nat Rev Cancer. 2023 Dec;23(12):805-824. doi: 10.1038/s41568-023-00623-0. Epub 2023 Oct 19.

ABSTRACT

Adrenocortical carcinoma is a rare malignancy with an annual worldwide incidence of 1-2 cases per 1 million and a 5-year survival rate of <60%. Although adrenocortical carcinoma is rare, such rare cancers account for approximately one third of patients diagnosed with cancer annually. In the past decade, there have been considerable advances in understanding the molecular basis of adrenocortical carcinoma. The genetic events associated with adrenocortical carcinoma in adults are distinct from those of paediatric cases, which are often associated with germline or somatic TP53 mutations and have a better prognosis. In adult primary adrenocortical carcinoma, the main somatic genetic alterations occur in genes that encode proteins involved in the WNT-β-catenin pathway, cell cycle and p53 apoptosis pathway, chromatin remodelling and telomere maintenance pathway, cAMP-protein kinase A (PKA) pathway or DNA transcription and RNA translation pathways. Recently, integrated molecular studies of adrenocortical carcinomas, which have characterized somatic mutations and the methylome as well as gene and microRNA expression profiles, have led to a molecular classification of these tumours that can predict prognosis and have helped to identify new therapeutic targets. In this Review, we summarize these recent translational research advances in adrenocortical carcinoma, which it is hoped could lead to improved patient diagnosis, treatment and outcome.

PMID:37857840 | DOI:10.1038/s41568-023-00623-0

Diagnostic and Prognostic Value of Neutrophil-Lymphocyte Ratio in Adrenocortical Carcinoma

Fetched: October 19th, 2023, 5:00am GMT by Chengquan Ma

Clin Genitourin Cancer. 2023 Oct 1:S1558-7673(23)00218-5. doi: 10.1016/j.clgc.2023.09.008. Online ahead of print.

ABSTRACT

BACKGROUND: The aim was to explore the value of neutrophil-lymphocyte ratio (NLR) as a biomarker for predicting the prognosis or diagnosis in adrenocortical carcinoma (ACC).

METHODS: We identified 262 patients with adrenal gland disease who underwent operation at our institution between 2013 and 2018. According to postoperative pathology, patients were divided into 2 groups: ACC and non-ACC groups. The neutrophil and lymphocyte count of patients were recorded. Within the intergroup comparison, data obtained from ACC and non-ACC groups were evaluated using ANOVA test. The cut-off values of NLR for the prognosis in ACC were determined according to 3 methods.

RESULTS: The NLR values of ACC and non-ACC groups were 5.36 ± 5.30 and (1.73 ± 0.26) ∼ (2.56 ± 1.35), respectively (P < .001). NLR carry a differential property was evaluated with ROC curve to distinguish the above 2 groups. The cut-off value of NLR was estimated as 2.65 according to the Youden index. With this value, sensitivity was found as 67.5%, specificity was 83.8% and AUC was 0.749 (P < .001, confidence interval = 0.638-0.860). In ACC, the higher NLR group was not shown significantly poorer overall survival than the lower NLR group (NLR ≥2.65 vs. NLR < 2.65, NLR ≥5 vs. NLR <5, NLR ≥5.36 vs. NLR <5.36) (P > .05).

CONCLUSION: According to the data in this study, it can be said that adrenocortical tumors are likely to be malignant by 67.5% if the NLR value is greater than 2.65. When we use the NLR to predict the prognosis of ACC, there is not statistically significant.

PMID:37852864 | DOI:10.1016/j.clgc.2023.09.008

Permalink for 'Identification of the ferroptosis regulator HELLS with prognostic value for adrenocortical carcinoma based on integrated analysis and experimental validation'

Identification of the ferroptosis regulator HELLS with prognostic value for adrenocortical carcinoma based on integrated analysis and experimental validation

Fetched: October 17th, 2023, 5:00am GMT by Zijian Liu

Gland Surg. 2023 Sep 25;12(9):1251-1270. doi: 10.21037/gs-22-736. Epub 2023 Sep 15.

ABSTRACT

BACKGROUND: For adrenocortical carcinoma (ACC), a rare endocrine malignancy with a high rate of mortality and recurrence, it is difficult for clinicians to predict overall survival and select the most effective treatment. Targeting ferroptosis, a form of cell death, has been reported to be a promising therapeutic strategy for ACC; however, the core ferroptosis regulator and its prognostic value in ACC remain unknown.

METHODS: RNA sequencing data and clinical information were downloaded from public databases. Differentially expressed gene and survival analyses were performed to identify candidate ferroptosis regulators. A multivariate Cox regression model was used to construct a gene signature, and a nomogram was constructed to predict the overall survival of patients with ACC. Gene set variation analysis (GSVA) was used to identify underlying aberrant pathways and the relative immune cell infiltration levels of each ACC sample. Immunohistochemistry staining was performed in formalin-fixed paraffin-embedded tumor tissue sections.

RESULTS: Ultimately, 23 differentially expressed ferroptosis regulators were identified between normal adrenal gland and ACC tissues, and 50 ferroptosis regulators were related to prognosis, with 13 ferroptosis regulators being simultaneously found to satisfy the differential expression and prognostic value. According to the multivariate Cox regression model, a ferroptosis regulator signature was constructed from 3 genes in The Cancer Genome Atlas (TCGA; hazard ratio =9.01; P=1.39×10^-10), and the area under the curve (AUC) values of 3-, 5-, 8-year overall survival were 0.924, 0.906, and 0.866, respectively. The survival analysis and the receiver operating characteristic (ROC) analysis validated the prognostic value of the ferroptosis regulator signature in 3 validation datasets. Moreover, metabolism-, E2F-, MYC-, and G2/M checkpoint-related pathways and aberrant immune cell infiltration levels were identified as being responsible for the different prognosis of risk groups in ACC. HELLS was found to be a significantly differentially expressed ferroptosis-suppressor gene with a prognostic value in ACC and to be highly associated with immune cell infiltration levels and multiple biological functions.

CONCLUSIONS: A ferroptosis regulator signature showed promising power for predicting the prognosis of ACC, and HELLS was identified as a hub ferroptosis regulator in the initiation and progression of ACC.

PMID:37842529 | PMC:PMC10570968 | DOI:10.21037/gs-22-736

Evaluating structure-based activity in a high-throughput assay for steroid biosynthesis

Fetched: October 17th, 2023, 5:00am GMT by M J Foster

Comput Toxicol. 2022 Nov 1;24:1-23. doi: 10.1016/j.comtox.2022.100245.

ABSTRACT

Data from a high-throughput human adrenocortical carcinoma assay (HT-H295R) for steroid hormone biosynthesis are available for >2000 chemicals in single concentration and 654 chemicals in multi-concentration (mc). Previously, a metric describing the effect size of a chemical on the biosynthesis of 11 hormones was derived using mc data referred to as the maximum mean Mahalanobis distance (maxmMd). However, mc HT-H295R assay data remain unavailable for many chemicals. This work leverages existing HT-H295R assay data by constructing structure-activity relationships to make predictions for data-poor chemicals, including: (1) identification of individual structural descriptors, known as ToxPrint chemotypes, associated with increased odds of affecting estrogen or androgen synthesis; (2) a random forest (RF) classifier using physicochemical property descriptors to predict HT-H295R maxmMd binary (positive or negative) outcomes; and, (3) a local approach to predict maxmMd binary outcomes using nearest neighbors (NNs) based on two types of chemical fingerprints (chemotype or Morgan). Individual chemotypes demonstrated high specificity (85-98%) for modulators of estrogen and androgen synthesis but with low sensitivity. The best RF model for maxmMd classification included 13 predicted physicochemical descriptors, yielding a balanced accuracy (BA) of 71% with only modest improvement when hundreds of structural features were added. The best two NN models for binary maxmMd prediction demonstrated BAs of 85 and 81% using chemotype and Morgan fingerprints, respectively. Using an external test set of 6302 chemicals (lacking HT-H295R data), 1241 were identified as putative estrogen and androgen modulators. Combined results across the three classification models (global RF model and two local NN models) predict that 1033 of the 6302 chemicals would be more likely to affect HT-H295R bioactivity. Together, these in silico approaches can efficiently prioritize thousands of untested chemicals for screening to further evaluate their effects on steroid biosynthesis.

PMID:37841081 | PMC:PMC10569244 | DOI:10.1016/j.comtox.2022.100245

Rare Tumors: Opportunities and challenges from the Children's Oncology Group perspective

Fetched: October 14th, 2023, 5:00am GMT by Kris Ann P Schultz

EJC Paediatr Oncol. 2023 Dec;2:100024. doi: 10.1016/j.ejcped.2023.100024. Epub 2023 Jul 20.

ABSTRACT

While all childhood cancers are rare, tumors that are particularly infrequent or underrepresented within pediatrics are studied under the umbrella of the Children's Oncology Group Rare Tumor committee, divided into the Retinoblastoma and Infrequent Tumor subcommittees. The Infrequent Tumor subcommittee has traditionally included an emphasis on globally rare tumors such as adrenocortical carcinoma, nasopharyngeal carcinoma, or those tumors that are rare in young children, despite being common in adolescents and young adults, such as colorectal carcinoma, thyroid carcinoma, and melanoma. Pleuropulmonary blastoma, gonadal stromal tumors, pancreatic tumors including pancreatoblastoma, gastrointestinal stromal tumor, nonmelanoma skin cancers, neuroendocrine tumors, and desmoplastic small round cell tumors, as well as other carcinomas are also included under the heading of the Children's Oncology Group Rare Tumor committee. While substantial challenges exist in rare cancers, inclusion and global collaboration remain key priorities to ensure high quality research to advance care.

PMID:37829670 | PMC:PMC10566015 | DOI:10.1016/j.ejcped.2023.100024

Pediatric adrenocortical carcinoma: clinical features and application of neoadjuvant chemotherapy

Fetched: October 10th, 2023, 5:00am GMT by Yu Lin

Eur J Med Res. 2023 Oct 9;28(1):411. doi: 10.1186/s40001-023-01381-3.

ABSTRACT

PMID:37814272 | PMC:PMC10563212 | DOI:10.1186/s40001-023-01381-3

Steroidogenic Factor-1 form and function: From phospholipids to physiology

Fetched: October 7th, 2023, 5:00am GMT by Alexis N Campbell

Adv Biol Regul. 2023 Sep 27:100991. doi: 10.1016/j.jbior.2023.100991. Online ahead of print.

ABSTRACT

Steroidogenic Factor-1 (SF-1, NR5A1) is a member of the nuclear receptor superfamily of ligand-regulated transcription factors, consisting of a DNA-binding domain (DBD) connected to a transcriptional regulatory ligand binding domain (LBD) via an unstructured hinge domain. SF-1 is a master regulator of development and adult function along the hypothalamic pituitary adrenal and gonadal axes, with strong pathophysiological association with endometriosis and adrenocortical carcinoma. SF-1 was shown to bind and be regulated by phospholipids, one of the most interesting aspects of SF-1 regulation is the manner in which SF-1 interacts with phospholipids: SF-1 buries the phospholipid acyl chains deep in the hydrophobic core of the SF-1 protein, while the lipid headgroups remain solvent-exposed on the exterior of the SF-1 protein surface. Here, we have reviewed several aspects of SF-1 structure, function and physiology, touching on other transcription factors that help regulate SF-1 target genes, non-canonical functions of SF-1, the DNA-binding properties of SF-1, the use of mass spectrometry to identify lipids that associate with SF-1, how protein phosphorylation regulates SF-1 and the structural biology of the phospholipid-ligand binding domain. Together this review summarizes the form and function of Steroidogenic Factor-1 in physiology and in human disease, with particular emphasis on adrenal cancer.

PMID:37802761 | DOI:10.1016/j.jbior.2023.100991

Permalink for 'Discovery of a glucocorticoid receptor (GR) activity signature correlates with immune cell infiltration in adrenocortical carcinoma'

Discovery of a glucocorticoid receptor (GR) activity signature correlates with immune cell infiltration in adrenocortical carcinoma

Fetched: October 5th, 2023, 5:00am GMT by Kan Wu

J Immunother Cancer. 2023 Oct;11(10):e007528. doi: 10.1136/jitc-2023-007528.

ABSTRACT

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and highly aggressive endocrine malignancy, of which >40% present with glucocorticoid excess. Glucocorticoids and glucocorticoid receptor (GR) signaling have long been thought to suppress immunity and promote tumor progression by acting on immune cells. Here, we provide new insights into the interaction between GR signaling activity and the immune signature of ACC as a potential explanation for immune escape and resistance to immunotherapy.

METHODS: First, GR immunohistochemical staining and immunofluorescence analysis of tumor-infiltrating lymphocyte (CD4 T, CD8 T cells, natural killer (NK) cells, dendritic cells and macrophages) were performed in 78 primary ACC tissue specimens. Quantitative data of immune cell infiltration in ACC were correlated with clinical characteristics. Second, we discovered a GR activity signature (GRsig) using GR-targeted gene networks derived from global gene expression data of primary ACC. Finally, we identified two GRsig-related subtypes based on the GRsig and assessed the differences in immune characteristics and prognostic stratification between the two subtypes.

RESULTS: GR was expressed in 90% of the ACC tumors, and CD8+ cytotoxic T lymphocytes were the most common infiltrating cell type in ACC specimens (88%, 8.6 cells/high power field). GR expression positively correlated with CD8+ T cell (Phi=0.342, p<0.001), CD4+ T cell (Phi=0.280, p<0.001), NK cell (Phi=0.280, p<0.001), macrophage (Phi=0.285, p<0.001), and dendritic cell (Phi=0.397, p<0.001) infiltration. Clustering heatmap analysis also displayed high immune cell infiltration in GR high-expressing tumors and low immune cell infiltration in GR-low tumors. High GR expression and high immune cell infiltration were significantly associated with better survival. Glucocorticoid excess is associated with low immune cell abundance and unfavorable prognosis. A GRsig comprizing n=34 GR-associated genes was derived from Gene Expression Omnibus/The Cancer Genome Atlas (TCGA) data sets and used to define two GRsig-related subtypes in the TCGA cohort. We demonstrated distinct differences in the immune landscape and clinical outcomes between the two subtypes.

CONCLUSION: GR expression positively correlates with tumor-infiltrating immune cells in ACC. The GRsig could serve as a prognostic biomarker and may be helpful for prognosis prediction and response to immunotherapy. Consequently, targeting the GR signaling pathway might be pivotal and should be investigated in clinical studies.

PMID:37793855 | PMC:PMC10551943 | DOI:10.1136/jitc-2023-007528

Inferior vena cava tumor thrombus: clinical outcomes at a canadian tertiary center

Fetched: September 30th, 2023, 5:00am GMT by Ali Fatehi Hassanabad

Perfusion. 2023 Sep 29:2676591231202682. doi: 10.1177/02676591231202682. Online ahead of print.

ABSTRACT

OBJECTIVE: This study reports the surgical management and outcomes of patients with malignancies affecting the IVC.

METHODS: This was a retrospective study that considered patients undergoing surgery for IVC thrombectomy in Calgary, Canada, from 1 January 2010 to 31 December 2021. Parameters of interest included primary malignancy, the extent of IVC involvement, surgical strategy, and medium-term outcomes.

RESULTS: Six patients underwent surgical intervention for malignancies that affected the IVC. One patient had a retroperitoneal leiomyosarcoma, 1 had hepatocellular carcinoma with thrombus extending into the IVC and right atrium, 1 had adrenocortical carcinoma with IVC thrombus extending into the right atrium, and 3 had clear cell renal cell carcinoma with thrombus extending into the IVC. Surgical strategy for the IVC thrombectomy varied where 5 patients required the institution of cardiopulmonary bypass and underwent deep hypothermic circulatory arrest. No patient died perioperatively. One patient died 15-months post-operatively from aggressive malignancy.

CONCLUSION: Different types of malignancy can affect the IVC and surgical intervention is usually indicated for these patients. Herein, we have reported the outcomes of IVC thrombectomy at our center.

PMID:37774418 | DOI:10.1177/02676591231202682

Permalink for 'Feasibility and Activity of Megestrol Acetate in Addition to Etoposide, Doxorubicin, Cisplatin, and Mitotane as First-Line Therapy in Patients with Metastatic/Unresectable Adrenocortical Carcinoma with Low Performance Status'

Feasibility and Activity of Megestrol Acetate in Addition to Etoposide, Doxorubicin, Cisplatin, and Mitotane as First-Line Therapy in Patients with Metastatic/Unresectable Adrenocortical Carcinoma with Low Performance Status

Fetched: September 29th, 2023, 5:00am GMT by Antonella Turla

Cancers (Basel). 2023 Sep 9;15(18):4491. doi: 10.3390/cancers15184491.

ABSTRACT

(1) Background: The standard first-line therapy for advanced adrenocortical carcinoma (ACC) is represented by EDP-M (etoposide, doxorubicin, cisplatin + mitotane). Progestins have shown cytotoxic activity both in vitro and in vivo on ACC; better EDP-M tolerability and efficacy have been hypnotized due to the association with progestins. (2) Methods: The feasibility and tolerability of EDP-M combined with oral megestrol acetate (EDP-MM) were tested in 24 patients (pts) affected by metastatic ACC with a low performance status (PS); the case group was compared with a 48 pts control group according to the propensity score. The secondary objectives were clinical benefit rate (CBR), progression-free survival (PFS), and overall survival (OS). (3) Results: Thirteen pts (54.2%) in the EDP-MM population experienced progestin-related toxicities; in particular, five pts experienced vaginal bleeding (20.8%); four pts experienced weight gain (16.7%); and thromboembolic events, worsening of hypertension, skin rashes, and hyperglycemia were registered in one patient each (4.2%). This led to the discontinuation of megestrol acetate in four pts (16.7%). EDP-M-related toxicities were similar in both groups. No differences in PFS and OS curves were observed; the CBR was 75.0% and 60.4%, respectively. (4) Conclusions: The association of EDP-M + megestrol acetate in ACC pts with a low PS is feasible and well tolerated; its efficacy appeared to be non-inferior to EDP-M administered to pts with a good PS.

PMID:37760461 | PMC:PMC10527072 | DOI:10.3390/cancers15184491

Permalink for 'Correction: Sigala et al. A Comprehensive Investigation of Steroidogenic Signaling in Classical and New Experimental Cell Models of Adrenocortical Carcinoma. Cells 2022, 11, 1439'

Correction: Sigala et al. A Comprehensive Investigation of Steroidogenic Signaling in Classical and New Experimental Cell Models of Adrenocortical Carcinoma. Cells 2022, 11, 1439

Fetched: September 29th, 2023, 5:00am GMT by Sandra Sigala

Cells. 2023 Sep 14;12(18):2274. doi: 10.3390/cells12182274.

ABSTRACT

The authors made the following changes to their paper [...].

PMID:37759554 | PMC:PMC10526947 | DOI:10.3390/cells12182274

Single and mixture toxicity evaluation of avobenzone and homosalate to male zebrafish and H295R cells

Fetched: September 28th, 2023, 5:01am GMT by Sujin Lee

Chemosphere. 2023 Dec;343:140271. doi: 10.1016/j.chemosphere.2023.140271. Epub 2023 Sep 25.

ABSTRACT

Avobenzone and homosalate are widely used in sunscreens to provide ultraviolet (UV) protection, either as single compounds or in combination. Some UV filters exhibit estrogenic or anti-androgenic activities, however, studies regarding their interactions and toxicity in mixtures are limited. In this study, the effect of the toxicity of a binary mixture comprising avobenzone (0.72 μg L^-1) and homosalate (1.02 and 103 μg L^-1) on steroid hormone biosynthesis were investigated using male zebrafish and human adrenocortical carcinoma (H295R) cells. In fish exposed to homosalate, a significant decrease in the gonadosomatic index, testosterone level, and transcription of several genes (e.g, hsd3b2, cyp17a1, and hsd17b1) and a significant increase in the hepatosomatic index, liver steatosis, 17β-estradiol level, and transcription of vtg gene were observed. These results suggest that estrogenic and anti-androgenic effects of homosalate were mediated by the steroidogenic pathway. The presence of 0.72 μg L^-1 of avobenzone augmented the anti-androgenic responses in male fish. The testosterone level in the H295R cells were significantly decreased after they were exposed to homosalate alone or in combination with avobenzone, which is consistent with observations in male zebrafish. Further studies need to be conducted to understand the endocrine disrupting properties of long-term exposure to substances typically used in sunscreens.

PMID:37758070 | DOI:10.1016/j.chemosphere.2023.140271

Permalink for 'High-Dose Rate Brachytherapy Combined with PD-1 Blockade as a Treatment for Metastatic Adrenocortical Carcinoma - A Single Center Case Series'

High-Dose Rate Brachytherapy Combined with PD-1 Blockade as a Treatment for Metastatic Adrenocortical Carcinoma - A Single Center Case Series

Fetched: September 26th, 2023, 5:00am GMT by Paul Schwarzlmueller

Horm Metab Res. 2023 Sep 25. doi: 10.1055/a-2150-3944. Online ahead of print.

ABSTRACT

The response rate of advanced adrenocortical carcinoma (ACC) to standard chemotherapy with mitotane and etoposide/doxorubicin/cisplatin (EDP-M) is unsatisfactory, and benefit is frequently short lived. Immune checkpoint inhibitors (CPI) have been examined in patient's refractory to EDP-M, but objective response rates are only approximately 15%. High-dose rate brachytherapy (HDR-BT) is a catheter-based internal radiotherapy and expected to favorably combine with immunotherapies. Here we describe three cases of patients with advanced ACC who were treated with HDR-BT and the CPI pembrolizumab. None of the tumors were positive for established response markers to CPI. All patients were female, had progressed on EDP-M and received external beam radiation therapy for metastatic ACC. Pembrolizumab was initiated 7 or 23 months after brachytherapy in two cases and prior to brachytherapy in one case. Best response of lesions treated with brachytherapy was complete (n=2) or partial response (n=1) that was ongoing at last follow up after 23, 45 and 4 months, respectively. Considering all sites of tumor, response was complete and partial remission in the two patients with brachytherapy prior to pembrolizumab. The third patient developed progressive disease with severe Cushing's syndrome and died due to COVID-19. Immune-related adverse events of colitis (grade 3), gastroduodenitis (grade 3), pneumonitis (grade 2) and thyroiditis (grade 1) occurred in the two patients with systemic response. HDR-BT controlled metastases locally. Sequential combination with CPI therapy may enhance an abscopal antitumoral effect in non-irradiated metastases in ACC. Systematic studies are required to confirm this preliminary experience and to understand underlying mechanisms.

PMID:37748508 | DOI:10.1055/a-2150-3944

Case Report: Response to ipilimumab and nivolumab in a patient with adrenocortical carcinoma

Fetched: September 26th, 2023, 5:00am GMT by Rebecca Charles

Front Oncol. 2023 Sep 8;13:1242560. doi: 10.3389/fonc.2023.1242560. eCollection 2023.

ABSTRACT

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare malignancy with limited treatment options. The evidence for the use of immunotherapy in ACC has been conflicting, with overall response rates ranging from 6 - 33%.

CASE PRESENTATION: We describe the case of a 32 year old patient who was initially thought to have an inoperable clear cell renal cell carcinoma and was treated with immunotherapy with ipilimumab and nivolumab. The patient had an excellent partial response to treatment. Further work-up prior to consideration of surgery demonstrated that the tumour was an ACC, rather than a renal cancer. She had a right adrenalectomy and right hepatectomy, achieving an R0 resection and remains disease-free one year after surgery.

CONCLUSION: This case illustrates the challenge of diagnosing ACC, and that doublet immunotherapy with ipilimumab and nivolumab can have significant clinical efficacy in ACC.

PMID:37746287 | PMC:PMC10516602 | DOI:10.3389/fonc.2023.1242560

Permalink for 'Case report: Remarkable response to a novel combination of mitotane, etoposide, paraplatin, and sintilimab in a patient with metastatic adrenocortical carcinoma'

Case report: Remarkable response to a novel combination of mitotane, etoposide, paraplatin, and sintilimab in a patient with metastatic adrenocortical carcinoma

Fetched: September 26th, 2023, 5:00am GMT by Yan Weng

Front Endocrinol (Lausanne). 2023 Sep 8;14:1115893. doi: 10.3389/fendo.2023.1115893. eCollection 2023.

ABSTRACT

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis and limited treatment options for metastases. However, new effective regimens are emerging for specific conditions in metastatic ACC.

CASE PRESENTATION: We report a case of a 36-year-old man diagnosed with metastatic ACC who had a large left adrenal mass (158 mm × 112 mm) and multiple metastases in the liver and lungs. Genetic testing revealed a microsatellite instability-high (MSI-H) tumor, a splice mutation in MLH1, and a high tumor mutational burden (TMB). After the left adrenalectomy, he received sequential treatment with a combination of mitotane, etoposide, paraplatin (EP-M), and sintilimab. His condition has been assessed as a stable disease since the sixth cycle of the combined regimen.

CONCLUSION: This case highlights the remarkable response of our patient's ACC with MSI-H tumor, MLH1 spice mutation, and high TMB to treatment with a novel combination of EP-M and sintilimab. Our findings suggest a promising therapeutic option for patients with similar molecular profiles.

PMID:37745701 | PMC:PMC10514511 | DOI:10.3389/fendo.2023.1115893

Permalink for 'Adrenal tumors treated by adrenalectomy following spontaneous rupture carry an overall favorable prognosis: retrospective evaluation of outcomes in 59 dogs and 3 cats (2000-2021)'

Adrenal tumors treated by adrenalectomy following spontaneous rupture carry an overall favorable prognosis: retrospective evaluation of outcomes in 59 dogs and 3 cats (2000-2021)

Fetched: September 22nd, 2023, 5:01am GMT by Marine Traverson

J Am Vet Med Assoc. 2023 Sep 21;261(12):1-9. doi: 10.2460/javma.23.06.0324. Print 2023 Dec 1.

ABSTRACT

OBJECTIVE: To conduct a retrospective multi-institutional study reporting short- and long-term outcomes of adrenalectomy in patients presenting with acute hemorrhage secondary to spontaneous adrenal rupture.

ANIMALS: 59 dogs and 3 cats.

METHODS: Medical records of dogs and cats undergoing adrenalectomy between 2000 and 2021 for ruptured adrenal masses were reviewed. Data collected included clinical presentation, preoperative diagnostics, surgical report, anesthesia and hospitalization findings, histopathology, adjuvant treatments, and long-term outcome (recurrence, metastasis, and survival).

RESULTS: Median time from hospital admission to surgery was 3 days, with 34% of surgeries being performed emergently (within 1 day of presentation). Need for intraoperative blood transfusion was significantly associated with emergent surgery and presence of active intraoperative hemorrhage. The short-term (≤ 14 days) complication and mortality rates were 42% and 21%, respectively. Negative prognostic factors for short-term survival included emergent surgery, intraoperative hypotension, and performing additional surgical procedures. Diagnoses included adrenocortical neoplasia (malignant [41%], benign [12%], and undetermined [5%]), pheochromocytoma (38%), a single case of adrenal fibrosis and hemorrhage (2%), and a single case of hemangiosarcoma (2%). Local recurrence and metastasis of adrenocortical carcinoma were confirmed in 1 and 3 cases, respectively. Overall median survival time was 574 days and 900 days when short-term mortality was censored. No significant relationship was found between histopathological diagnosis and survival.

CLINICAL RELEVANCE: Adrenalectomy for ruptured adrenal gland masses was associated with similar short- and long-term outcomes as compared with previously reported nonruptured cases. If hemodynamic stability can be achieved, delaying surgery and limiting additional procedures appear indicated to optimize short-term survival.

PMID:37734721 | DOI:10.2460/javma.23.06.0324

Permalink for 'A 3D adrenocortical carcinoma tumor platform for preclinical modeling of drug response and matrix metalloproteinase activity'

A 3D adrenocortical carcinoma tumor platform for preclinical modeling of drug response and matrix metalloproteinase activity

Fetched: September 20th, 2023, 5:00am GMT by Priya H Dedhia

Sci Rep. 2023 Sep 19;13(1):15508. doi: 10.1038/s41598-023-42659-0.

ABSTRACT

Adrenocortical carcinoma (ACC) has a poor prognosis, and no new drugs have been identified in decades. The absence of drug development can partly be attributed to a lack of preclinical models. Both animal models and 2D cell cultures of ACC fail to accurately mimic the disease, as animal physiology is inherently different than humans, and 2D cultures fail to represent the crucial 3D architecture. Organoids and other small 3D in vitro models of tissues or tumors can model certain complexities of human in vivo biology; however, this technology has largely yet to be applied to ACC. In this study, we describe the generation of 3D tumor constructs from an established ACC cell line, NCI-H295R. NCI-H295R cells were encapsulated to generate 3D ACC constructs. Tumor constructs were assessed for biomarker expression, viability, proliferation, and cortisol production. In addition, matrix metalloproteinase (MMP) functionality was assessed directly using fluorogenic MMP-sensitive biosensors and through infusion of NCI-H295R cells into a metastasis-on-a-chip microfluidic device platform. ACC tumor constructs showed expression of biomarkers associated with ACC, including SF-1, Melan A, and inhibin α. Treatment of ACC tumor constructs with chemotherapeutics demonstrated decreased drug sensitivity compared to 2D cell culture. Since most tumor cells migrate through tissue using MMPs to break down extracellular matrix, we validated the utility of ACC tumor constructs by integrating fluorogenic MMP-sensitive peptide biosensors within the tumor constructs. Lastly, in our metastasis-on-a-chip device, NCI-H295R cells successfully engrafted in a downstream lung cell line-based construct, but invasion distance into the lung construct was decreased by MMP inhibition. These studies, which would not be possible using 2D cell cultures, demonstrated that NCI-H295R cells secreted active MMPs that are used for invasion in 3D. This work represents the first evidence of a 3D tumor constructs platform for ACC that can be deployed for future mechanistic studies as well as development of new targets for intervention and therapies.

PMID:37726363 | PMC:PMC10509170 | DOI:10.1038/s41598-023-42659-0

Permalink for 'Two-dimensional chromatography for enantiomeric analysis of mitotane and its metabolite o,p'-DDA in patients with adrenocortical carcinoma indicates enantioselective metabolism'

Two-dimensional chromatography for enantiomeric analysis of mitotane and its metabolite o,p'-DDA in patients with adrenocortical carcinoma indicates enantioselective metabolism

Fetched: September 17th, 2023, 5:00am GMT by Gabriela Stadler

Bioorg Chem. 2023 Dec;141:106835. doi: 10.1016/j.bioorg.2023.106835. Epub 2023 Sep 3.

ABSTRACT

Mitotane is a chiral drug used to treat adrenocortical carcinoma, being metabolized to the o,p'-dichlorodiphenyl acetic acid (o,p'-DDA), also a chiral compound. Despite of its therapeutic significance, the overall ratios and enantiomers have not been known. In this study, we analyzed the enantiomers of mitotane and o,p'-DDA in the plasma of patients by a newly developed chiral-phase method employed in two-dimensional chromatography. Important differences were observed in the ratio of (S)/(R)-mitotane, which varied substantially from 1:1.2 to 1:10 whereas the (S)/(R)-o,p'-DDA ratio was relatively conserved, at approximately 2:1. These findings provide evidence for the enantioselective metabolism and provide a method for further analyses of mitotane and metabolites, which can explain the variation in the therapeutic response.

PMID:37713949 | DOI:10.1016/j.bioorg.2023.106835

Case Report Of A Rare Incidentaloma Of The Adrenal Gland-Schwannoma

Fetched: September 13th, 2023, 5:00am GMT by Usama Muhammad Kathia

J Pak Med Assoc. 2023 Aug;73(8):1726-1728. doi: 10.47391/JPMA.7310.

ABSTRACT

The Schwannoma is a benign growth of the nerve sheath cells most commonly seen in the vestibulocochlear nerve. Its prevalence in the adrenal gland is 1-3%. Here we discuss a case that presented as an incidentaloma of the right adrenal gland in a young male patient who had vague abdominal symptoms and a normal hormonal profile. He underwent an excisional biopsy of the right adrenal gland due to the large size of the lesion (more than 4cm). The histopathology report helped to establish the diagnosis of Schwannoma. Incidentaloma is defined as a lesion of the adrenal gland encountered on any radiological investigation carried out for symptoms that are not associated with adrenal pathologies. After discovering such lesions, it is imperative to perform radiological and hormonal investigations in an organised manner to plan further management of such cases.

PMID:37697772 | DOI:10.47391/JPMA.7310

Intratumour microbiota modulates adrenocortical cancer responsiveness to mitotane

Fetched: September 12th, 2023, 5:00am GMT by Giulia Cantini

Endocr Relat Cancer. 2023 Sep 11;30(10):e230094. doi: 10.1530/ERC-23-0094. Print 2023 Oct 1.

ABSTRACT

The infiltrating microbiota represents a novel cellular component of the solid tumour microenvironment that can influence tumour progression and response to therapy. Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy for which mitotane (MTT) treatment represents the first-line therapy, though its efficacy is limited to a therapeutic window level (14-20 mg/L). Novel markers able to predict those patients who would benefit from MTT therapy are urgently needed to improve patient's management. The aim of our study was to evaluate the presence of intratumoural bacterial microbiota DNA in 26 human ACC tissues vs 9 healthy adrenals; moreover, the association between the relative bacterial composition profile, the tumour mass characteristics and MTT ability to reach high circulating levels in the early phase of treatment, were explored. We found the presence of bacterial DNA in all adrenal samples from both tumours and healthy cortex specimens, documenting significant differences in the microbial composition between malignancy and normal adrenals: in detail, the ACC tissues were characterised by a higher abundance of the Proteobacteria phylum (especially the Pseudomonas and Serratia genera). In addition, the Proteobacteria's low abundance was negatively associated with tumour size, Ki67 and cortisol secretion. MTT levels reached higher levels at 9 months in ACC patients with high abundance of Proteobacteria, Pseudomonas and Serratia and with low abundance of Bacteroidota, Firmicutes and Streptococcus. These findings are the first indication that human ACCs are characterised by infiltrating bacteria and their specific abundance profile seems to influence the increase in circulating MTT levels at 9 months.

PMID:37695690 | PMC:PMC10502960 | DOI:10.1530/ERC-23-0094

Adrenocortical carcinoma: Diagnosis, prognostic classification and treatment of localized and advanced disease

Fetched: September 11th, 2023, 5:00am GMT by Rossella Libé

Cancer Treat Res Commun. 2023 Sep 8;37:100759. doi: 10.1016/j.ctarc.2023.100759. Online ahead of print.

ABSTRACT

Adrenocortical carcinoma (ACC) is a rare cancer with an estimated incidence of 0.7 to 2.0 cases per 1 million population per year in the United States. It is an aggressive cancer originating in the cortex of the adrenal gland with a poor prognosis. The 5-year survival rate is less than 15% among patients with metastatic disease. In this article, we review the epidemiology and pathogenesis of ACC, the diagnostic procedures, the prognostic classification of ACC, and the treatment options from localized and resectable forms to advanced disease detailing recent therapeutic developments such as immunotherapy and molecularly targeted therapy.

PMID:37690343 | DOI:10.1016/j.ctarc.2023.100759

Locally Advanced Adrenocortical Carcinoma in Children and Adolescents-Enigmatic and Challenging Cases

Fetched: September 10th, 2023, 5:00am GMT by Michaela Kuhlen

Cancers (Basel). 2023 Aug 28;15(17):4296. doi: 10.3390/cancers15174296.

ABSTRACT

BACKGROUND: Locally advanced tumors account for approximately 50% of children and adolescents with adrenocortical carcinoma (ACC), and of these, up to 50% relapse. We explored the five-item microscopic score and the pS-GRAS score for guiding management.

METHODS: Data from children and adolescents with COG stage II and III ACC registered in the MET studies were included. The five-item and pS-GRAS score were retrospectively calculated.

RESULTS: By December 2021, 55 patients with stage II and III (stage II n = 18, stage III n = 37) had been reported. Median age was 4.3 years [0.1-17.8], median duration of follow-up 6.0 years [0-16.7]. 3-year event-free survival (EFS) rate was 76.5% and 49.8% (p = 0.088), respectively. In stage II tumors, neither the five-item score (p = 0.872) nor pS-GRAS grouping (p = 0.218) had any effect as prognostic factors. In stage III patients, EFS was impaired in tumors with unfavorable histology according to the five-item score (100% vs. 30.8%, p = 0.018). No difference was observed for pS-GRAS groups (p = 0.798).

CONCLUSIONS: In patients with COG stage III, but not stage II, the five-item score affected EFS. Further studies are needed to identify patients at risk in COG stage II.

PMID:37686571 | PMC:PMC10486626 | DOI:10.3390/cancers15174296

Right Adrenocortical Carcinoma Coexisting With Left Adrenal Sarcomatoid Carcinoma on FDG PET/CT

Fetched: September 9th, 2023, 5:00am GMT by Haotian Chen

Clin Nucl Med. 2023 Oct 1;48(10):e503-e505. doi: 10.1097/RLU.0000000000004797. Epub 2023 Sep 2.

ABSTRACT

Bilateral adrenal glands synchronously involved by different types of pathologies are uncommon. An 80-year-old man underwent FDG PET/CT to evaluate bilateral adrenal masses, which were initially discovered by ultrasonography and confirmed by MRI. The images demonstrated elevated FDG activity in both lesions, which were subsequently diagnosed as concurrent right adrenocortical carcinoma and left adrenal sarcomatoid carcinoma respectively by histopathological examination.

PMID:37682621 | DOI:10.1097/RLU.0000000000004797

Permalink for 'Identification of the H3K36me3 reader LEDGF/p75 in the pancancer landscape and functional exploration in clear cell renal cell carcinoma'

Identification of the H3K36me3 reader LEDGF/p75 in the pancancer landscape and functional exploration in clear cell renal cell carcinoma

Fetched: September 8th, 2023, 5:00am GMT by Yuwei Zhang

Comput Struct Biotechnol J. 2023 Aug 26;21:4134-4148. doi: 10.1016/j.csbj.2023.08.023. eCollection 2023.

ABSTRACT

Lens epithelium-derived growth factor (LEDGF/p75) is a reader of epigenetic marks and a potential target for therapeutic intervention. Its involvement in human immunodeficiency virus (HIV) integration and the development of leukemia driven by MLL (also known as KMT2A) gene fusion make it an attractive candidate for drug development. However, exploration of LEDGF/p75 as an epigenetic reader of H3K36me3 in tumors is limited. Here, for the first time, we analyze the role of LEDGF/p75 in multiple cancers via multiple online databases and in vitro experiments. We used pancancer bulk sequencing data and online tools to analyze correlations of LEDGF/p75 with prognosis, genomic instability, DNA damage repair, prognostic alternative splicing, protein interactions, and tumor immunity. In summary, the present study identified that LEDGF/p75 may serve as a prognostic predictor for tumors such as adrenocortical carcinoma, kidney chromophobe, liver hepatocellular carcinoma, pancreatic adenocarcinoma, skin cutaneous melanoma, and clear cell renal cell carcinoma (ccRCC). In addition, in vitro experiments and gene microarray sequencing were performed to explore the function of LEDGF/p75 in ccRCC, providing new insights into the pathogenesis of the nonmutated SETD2 ccRCC subtype.

PMID:37675289 | PMC:PMC10477754 | DOI:10.1016/j.csbj.2023.08.023

SLC10A3 Is a Prognostic Biomarker and Involved in Immune Infiltration and Programmed Cell Death in Lower Grade Glioma

Fetched: September 1st, 2023, 5:00am GMT by Weibo Ma

World Neurosurg. 2023 Oct;178:e595-e640. doi: 10.1016/j.wneu.2023.07.134. Epub 2023 Aug 4.

ABSTRACT

BACKGROUND: The association between SLC10A3 (solute carrier family 10 member 3) and lower grade glioma (LGG) remains unclear.

METHODS: We used public databases and bioinformatics analysis to analyze SLC10A3. These included The Cancer Genome Atlas, Genotype-Tissue Expansion, Chinese Glioma Genome Atlas, Human Protein Atlas, GeneCards, cBioPortal, Search Tool for the Retrieval of Interacting Genes/Proteins, Gene Expression Profiling Interactive Analysis, Tumor Immune Estimation Resource, Tumor-Immune System Interaction Database, receiver operating characteristic curve analysis, Kaplan-Meier analysis, Cox analysis, nomograms, calibration plots, gene ontology/Kyoto Encyclopedia of Genes and Genomes enrichment analysis, gene set enrichment analysis, single-sample gene set enrichment analysis, and Spearman's correlation analysis.

RESULTS: SLC10A3 was upregulated in adrenocortical carcinoma, glioblastoma, and LGG and was associated with good overall survival (OS) in adrenocortical carcinoma and poor OS in LGG and glioblastoma. SLC10A3 was increased with increased World Health Organization grade, upregulated in isocitrate dehydrogenase-wild type, 1p/19q (chromosome arms 1p and 19q) non-co-deleted, and higher in astrocytoma. Patients with LGG were grouped by the occurrence of the clinical outcome endpoints (i.e., OS, disease-specific survival [DSS], and progression-free interval events). Genetic alterations in SLC10A3 were associated with poor progression-free survival in LGG. Most of clinical characteristics were associated with the SLC10A3 expression level. SLC10A3 with diagnostic and prognostic value (OS, DSS, and progression-free interval) was an independent prognostic factor in LGG. Moreover, Nomograms (WHO grade, 1p/19q codeletion, age and SLC10A3) had moderately accurate predictive for OS and DSS. Functional analysis showed that SLC10A3 might participate in the transport of multiple substances, neurogenic signaling, immune response, and programmed cell death in LGG. SLC10A3 correlated with immune infiltration in LGG and moderately correlated with the gene signature of pyroptosis, lysosome-dependent cell death, necroptosis, apoptosis, ferroptosis, alkaliptosis, and autophagy-dependent cell death.

CONCLUSIONS: SLC10A3 is a potential diagnostic and prognostic biomarker for LGG and might be associated with substance transport, neurogenic signaling, immune infiltration, and programmed cell death in LGG.

PMID:37543196 | DOI:10.1016/j.wneu.2023.07.134

The asymmetric adrenals: Sexual dimorphism of adrenal tumours

Fetched: August 31st, 2023, 5:00am GMT by Nicole Bechmann

J Clin Endocrinol Metab. 2023 Aug 30:dgad515. doi: 10.1210/clinem/dgad515. Online ahead of print.

ABSTRACT

CONTEXT: Sexual dimorphism has direct consequences on the incidence and survival of cancer. Early and accurate diagnosis is crucial to improve prognosis.

OBJECTIVE: This work aimed to characterised the influence of sex and adrenal asymmetry on the emergence of adrenal tumours.

METHODS: We conducted a multicentre, observational study involving 8037 patients with adrenal tumours, including adrenocortical carcinoma (ACC), aldosterone-producing adenoma (APA), cortisol-secreting adrenocortical adenomas (CSAs), non-aldosterone producing adrenal cortical adenoma (NAPACA), phaeochromocytoma and neuroblastoma, and investigated tumour lateralisation according to sex. Human adrenal tissues (n=20) were analysed with a multi-omics approach that allows determination of gene expression, catecholamine and steroid contents in a single sample. In addition, we performed a literature review of computed tomography and magnetic resonance imaging-based studies examining adrenal gland size.

RESULTS: ACC (n=1858); CSA (n=68), NAPACA (n=2174) and phaeochromocytoma (n=1824) were more common in females than in males (female-to-male ratio: 1.1:1 - 3.8:1), while neuroblastomas (n=2320) and APAs (n=228) were less prevalent in females (0.8:1). ACC, APA, CSA, NAPACA and neuroblastoma occurred more frequently in the left than in the right adrenal (left-to-right ratio: 1.1:1-1.8:1), whereas phaeochromocytoma arose more often in the right than in the left adrenal (0.8:1). In both sexes, the left adrenal was larger than the right adrenal, whereby females have smaller adrenals than males.

CONCLUSION: Adrenal asymmetry in both sexes may be related to the pathogenesis of adrenal tumours and should be considered during the diagnosis of these tumours.

PMID:37647861 | DOI:10.1210/clinem/dgad515

A retroperitoneal ectopic adrenocortical carcinoma in a patient with Cushing's syndrome

Fetched: August 31st, 2023, 5:00am GMT by Carol D Cardona Attard

Br J Hosp Med (Lond). 2023 Aug 2;84(8):1-4. doi: 10.12968/hmed.2023.0097. Epub 2023 Aug 16.

NO ABSTRACT

PMID:37646544 | DOI:10.12968/hmed.2023.0097

Neurological adverse events of mitotane in adrenocortical carcinoma: results of a pilot study

Fetched: August 31st, 2023, 5:00am GMT by Marilda Mormando

Front Oncol. 2023 Aug 14;13:1222002. doi: 10.3389/fonc.2023.1222002. eCollection 2023.

ABSTRACT

INTRODUCTION: Mitotane, the only drug approved by the Food and Drug Administration (FDA) for the treatment of adrenocortical carcinoma, is associated with several side effects including neurotoxicity. The aim of our study is to investigate the relationship between mitotane plasma levels and neurological toxicity.

METHODS: We have considered five patients affected by adrenocortical carcinoma treated with mitotane. The neurological assessment included a neurological examination, an electroencephalogram, event-related potentials (P300), and a neuropsychological assessment. All of the patients were first considered at the onset of symptoms of neurotoxicity or when mitotanemia levels were above 18 mg/L, for the second time at mitotanemia normalization and subsequently at its further increase, or in case of persistent neurological abnormalities, some months after normalization.

RESULTS: At the first neurotoxicity, four patients showed impaired neurological examination, electroencephalogram, and P300; three patients had impaired neuropsychological assessment; one patient, only P300. At mitotanemia normalization, the neurological examination became normal in all patients and electroencephalogram normalized in one patient, improved in another one, continuing to be altered in the other three. P300 latency and neuropsychological assessment normalized in two patients and persisted altered in the patient experiencing long-term mitotane toxicity. At the third evaluation, in the patient with prolonged mitotane toxicity, the normal mitotanemia in the previous 9 months restored P300 and improved the electroencephalogram but not the neuropsychological assessment. In the two patients experiencing a further rise of mitotanemia, neurological examination was normal but P300 and electroencephalogram were altered.

CONCLUSION: The results of our study highlighted the presence of neurophysiological and neuropsychological abnormalities associated with mitotane values above 18 mg/L.

PMID:37645432 | PMC:PMC10461107 | DOI:10.3389/fonc.2023.1222002

Pan-cancer atlas of somatic core and linker histone mutations

Fetched: August 29th, 2023, 5:00am GMT by Erin R Bonner

NPJ Genom Med. 2023 Aug 28;8(1):23. doi: 10.1038/s41525-023-00367-8.

ABSTRACT

Recent genomic data points to a growing role for somatic mutations altering core histone and linker histone-encoding genes in cancer. However, the prevalence and the clinical and biological implications of histone gene mutations in malignant tumors remain incompletely defined. To address these knowledge gaps, we analyzed somatic mutations in 88 linker and core histone genes across 12,743 tumors from pediatric, adolescent and young adult (AYA), and adult cancer patients. We established a pan-cancer histone mutation atlas contextualized by patient age, survival outcome, and tumor location. Overall, 11% of tumors harbored somatic histone mutations, with the highest rates observed among chondrosarcoma (67%), pediatric high-grade glioma (pHGG, >60%), and lymphoma (>30%). Previously unreported histone mutations were discovered in pHGG and other pediatric brain tumors, extending the spectrum of histone gene alterations associated with these cancers. Histone mutation status predicted patient survival outcome in tumor entities including adrenocortical carcinoma. Recurrent pan-cancer histone mutation hotspots were defined and shown to converge on evolutionarily conserved and functional residues. Moreover, we studied histone gene mutations in 1700 pan-cancer cell lines to validate the prevalence and spectrum of histone mutations seen in primary tumors and derived histone-associated drug response profiles, revealing candidate drugs targeting histone mutant cancer cells. This study presents the first-of-its-kind atlas of both core and linker histone mutations across pediatric, AYA, and adult cancers, providing a framework by which specific cancers may be redefined in the context of histone and chromatin alterations.

PMID:37640703 | PMC:PMC10462747 | DOI:10.1038/s41525-023-00367-8

Expression of EMP 1, 2, and 3 in Adrenal Cortical Neoplasm and Pheochromocytoma

Fetched: August 29th, 2023, 5:00am GMT by Yoon Jin Cha

Int J Mol Sci. 2023 Aug 21;24(16):13016. doi: 10.3390/ijms241613016.

ABSTRACT

The purpose of this study is to investigate the expression of the epithelial membrane proteins (EMP) 1, 2, and 3 in adrenal gland neoplasm and to explore the broader implications of this. Tissue microarrays were constructed for 132 cases of adrenal cortical neoplasms (ACN) (adrenal cortical adenoma (115 cases), and carcinoma (17 cases)) and 189 cases of pheochromocytoma. Immunohistochemical staining was performed to identify EMP 1, 2, and 3, and was compared with clinicopathological parameters. The H-score of EMP 3 (p < 0.001) was higher in pheochromocytoma when compared to that of ACN, and the H-score of EMP 1 (p < 0.001) and EMP 3 (p < 0.001) was higher in adrenal cortical carcinomas when compared to that of adrenal cortical adenomas. A higher EMP 1 H-score was observed in pheochromocytomas with a GAPP score ≥3 (p = 0.018). In univariate analysis, high levels of EMP 1 and EMP 3 expression in ACN were associated with shorter overall survival (p = 0.001). Differences were observed in the expression of EMPs between ACN and pheochromocytoma. EMPs are associated with malignant tumor biology in adrenal cortical neoplasm and pheochromocytoma, suggesting the role of a prognostic and/or predictive factor for EMPs in adrenal tumor.

PMID:37629198 | PMC:PMC10455306 | DOI:10.3390/ijms241613016

Good news for patients with adrenocortical carcinoma from the ADIUVO trial

Fetched: August 25th, 2023, 5:00am GMT by Martin Reincke

Lancet Diabetes Endocrinol. 2023 Oct;11(10):708-709. doi: 10.1016/S2213-8587(23)00231-0. Epub 2023 Aug 21.

NO ABSTRACT

PMID:37619580 | DOI:10.1016/S2213-8587(23)00231-0

Permalink for 'Adjuvant mitotane versus surveillance in low-grade, localised adrenocortical carcinoma (ADIUVO): an international, multicentre, open-label, randomised, phase 3 trial and observational study'

Adjuvant mitotane versus surveillance in low-grade, localised adrenocortical carcinoma (ADIUVO): an international, multicentre, open-label, randomised, phase 3 trial and observational study

Fetched: August 25th, 2023, 5:00am GMT by Massimo Terzolo

Lancet Diabetes Endocrinol. 2023 Oct;11(10):720-730. doi: 10.1016/S2213-8587(23)00193-6. Epub 2023 Aug 21.

ABSTRACT

BACKGROUND: Adjuvant treatment with mitotane is commonly used after resection of adrenocortical carcinoma; however, treatment remains controversial, particularly if risk of recurrence is not high. We aimed to assess the efficacy and safety of adjuvant mitotane compared with surveillance alone following complete tumour resection in patients with adrenocortical carcinoma considered to be at low to intermediate risk of recurrence.

METHODS: ADIUVO was a multicentre, open-label, parallel, randomised, phase 3 trial done in 23 centres across seven countries. Patients aged 18 years or older with adrenocortical carcinoma and low to intermediate risk of recurrence (R0, stage I-III, and Ki67 ≤10%) were randomly assigned to adjuvant oral mitotane two or three times daily (the dose was adjusted by the local investigator with the target of reaching and maintaining plasma mitotane concentrations of 14-20 mg/L) for 2 years or surveillance alone. All consecutive patients at 14 study centres fulfilling the eligibility criteria of the ADIUVO trial who refused randomisation and agreed on data collection via the European Network for the Study of Adrenal Tumors adrenocortical carcinoma registry were included prospectively in the ADIUVO Observational study. The primary endpoint was recurrence-free survival, defined as the time from randomisation to the first radiological evidence of recurrence or death from any cause (whichever occurred first), assessed in all randomly assigned patients by intention to treat. Overall survival, defined as time from the date of randomisation to the date of death from any cause, was a secondary endpoint analysed by intention to treat in all randomly assigned patients. Safety was assessed in all patients who adhered to the assigned regimen, which was defined by taking at least one tablet of mitotane in the mitotane group and no mitotane at all in the surveillance group. The ADIUVO trial is registered with ClinicalTrials.gov, NCT00777244, and is now complete.

FINDINGS: Between Oct 23, 2008, and Dec 27, 2018, 45 patients were randomly assigned to mitotane and 46 to surveillance alone. Because the study was discontinued prematurely, 5-year recurrence-free and overall survival are reported instead of recurrence-free and overall survival as defined in the protocol. 5-year recurrence-free survival was 79% (95% CI 67-94) in the mitotane group and 75% (63-90) in the surveillance group (hazard ratio 0·74 [95% CI 0·30-1·85]). Two people in the mitotane group and five people in the surveillance group died, and 5-year overall survival was not significantly different (95% [95% CI 89-100] in the mitotane group and 86% [74-100] in the surveillance group). All 42 patients who received mitotane had adverse events, and eight (19%) discontinued treatment. There were no grade 4 adverse events or treatment-related deaths.

INTERPRETATION: Adjuvant mitotane might not be indicated in patients with low-grade, localised adrenocortical carcinoma considering the relatively good prognosis of these patients, and no significant improvement in recurrence-free survival and treatment-associated toxicity in the mitotane group. However, the study was discontinued prematurely due to slow recruitment and cannot rule out an efficacy of treatment.

FUNDING: AIFA, ENSAT Cancer Health F2-2010-259735 programme, Deutsche Forschungsgemeinschaft, Cancer Research UK, and the French Ministry of Health.

PMID:37619579 | PMC:PMC10522778 | DOI:10.1016/S2213-8587(23)00193-6

Metabolic heterogeneity in adrenocortical carcinoma impacts patient outcomes

Fetched: August 23rd, 2023, 5:00am GMT by Qian Wang

JCI Insight. 2023 Aug 22;8(16):e167007. doi: 10.1172/jci.insight.167007.

ABSTRACT

Spatially resolved metabolomics enables the investigation of tumoral metabolites in situ. Inter- and intratumor heterogeneity are key factors associated with patient outcomes. Adrenocortical carcinoma (ACC) is an exceedingly rare tumor associated with poor survival. Its clinical prognosis is highly variable, but the contributions of tumor metabolic heterogeneity have not been investigated thus far to our knowledge. An in-depth understanding of tumor heterogeneity requires molecular feature-based identification of tumor subpopulations associated with tumor aggressiveness. Here, using spatial metabolomics by high-mass resolution MALDI Fourier transform ion cyclotron resonance mass spectrometry imaging, we assessed metabolic heterogeneity by de novo discovery of metabolic subpopulations and Simpson's diversity index. After identification of tumor subpopulations in 72 patients with ACC, we additionally performed a comparison with 25 tissue sections of normal adrenal cortex to identify their common and unique metabolic subpopulations. We observed variability of ACC tumor heterogeneity and correlation of high metabolic heterogeneity with worse clinical outcome. Moreover, we identified tumor subpopulations that served as independent prognostic factors and, furthermore, discovered 4 associated anticancer drug action pathways. Our research may facilitate comprehensive understanding of the biological implications of tumor subpopulations in ACC and showed that metabolic heterogeneity might impact chemotherapy.

PMID:37606037 | PMC:PMC10543722 | DOI:10.1172/jci.insight.167007

Cortisol-Producing Adrenocortical Carcinoma Presenting with Hypertensive Emergency

Fetched: August 23rd, 2023, 5:00am GMT by Mitchell McGowan

Am J Case Rep. 2023 Aug 22;24:e940228. doi: 10.12659/AJCR.940228.

ABSTRACT

BACKGROUND Hypertensive crisis is a relatively common condition often due to uncontrolled essential hypertension, but also potentially driven by one of many possible secondary etiologies. In this report, we detail a case of new-onset resistant hypertension leading to hypertensive emergency complicated by myocardial infarction and congestive heart failure secondary to underlying cortisol-producing metastatic adrenocortical carcinoma. CASE REPORT A 57-year-old woman with no past medical history presented with generalized weakness and weight gain. Her blood pressure was 239/141 with a pulse of 117. Other vital signs were normal. A physical exam was notable for obesity and lower-extremity edema. Initial ser

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