Rare Cancer News & Clinical Trials » Adrenal Gland Cancer

Adrenal Gland Cancer (453 unread)

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Permalink for 'Transhiatal/Transabdominal Approach Compare With Thoracoabdominal Approach for Siewert II Adenocarcinoma of Esophagogastric Junction'

Transhiatal/Transabdominal Approach Compare With Thoracoabdominal Approach for Siewert II Adenocarcinoma of Esophagogastric Junction

Posted: June 2nd, 2021, 2:00pm GMT

Condition: Adenocarcinoma of Esophagogastric Junction
Interventions: Procedure: transhiatal/transabdominal approach; Procedure: thoracoabdominal approach
Sponsor: Chinese PLA General Hospital
Recruiting

Permalink for 'Effect of Multi-modal Intervention Care on Cachexia in Patients With Advanced Cancer Compared to Conventional Management (MIRACLE)'

Effect of Multi-modal Intervention Care on Cachexia in Patients With Advanced Cancer Compared to Conventional Management (MIRACLE)

Posted: May 31st, 2021, 2:00pm GMT

Conditions: Gastric Cancer; Colorectal Cancer; Pancreatic Cancer; Biliary Tract Cancer; Lung Cancer; Precachexia; Cachexia
Intervention: Combination Product: Multi-modal intervention
Sponsors: Kil Yeon Lee; National Research Foundation of Korea
Recruiting

3D Laparoscopic Adrenalectomies for Adrenal Tumors

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

Conditions: Adrenal Tumor; Adrenalectomy; Status
Intervention:
Sponsor: 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
Not yet recruiting

Adrenomedullin in Context With Pulmonary Embolism

Posted: May 6th, 2021, 2:00pm GMT

Condition: Pulmonary Embolism
Intervention: Diagnostic Test: blood samples
Sponsor: University of Pecs
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
Not yet recruiting

Gallium-68 Labeled Pentixafor PET/CT in Adrenal Masses

Posted: April 26th, 2021, 2:00pm GMT

Condition: Adrenal Mass
Intervention: Diagnostic Test: Gallium-68 Pentixafor PET/CT
Sponsor: Peking Union Medical College Hospital
Recruiting

National Project on Vaccines, COVID-19 and Frail Patients

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

Conditions: COVID-19; Solid Tumor; Hematologic Diseases; Neurologic Disorder; Rheumatic Diseases
Intervention: Biological: COVID-19 vaccines
Sponsors: Azienda Unità Sanitaria Locale Reggio Emilia; Fondazione IRCCS Istituto Nazionale dei Tumori, Milano; Istituto Clinico Humanitas; IRCCS San Raffaele; Regina Elena Cancer Institute; Istituto Nazionale per le Malattie Infettive "Lazzaro Spallanzani" IRCCS; University of Roma La Sapienza; Fondazione IRCCS Policlinico San Matteo di Pavia; Istituti Fisioterapici Ospitalieri; Istituto Tumori Giovanni Paolo II, BARI; Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta; IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy; IRCCS Azienda Ospedaliero-Universitaria di Bologna
Recruiting

Phase I Study of Intratumor Injection of Anti-Mesothelin Immunotoxin LMB-100 With Ipilimumab in Malignant Mesothelioma

Posted: April 12th, 2021, 2:00pm GMT

Condition: Mesothelioma
Interventions: Biological: LMB-100; Drug: ipilimumab
Sponsor: National Cancer Institute (NCI)
Recruiting

Stereotactic Ablative Radiation Therapy for Abiraterone-Resistant, Oligoprogressive Metastatic Prostate Cancer

Posted: April 9th, 2021, 2:00pm GMT

Conditions: Oligoprogressive; Castration-Resistant Prostate Cancer
Intervention: Radiation: Stereotactic Body Radiation Therapy (SABR)
Sponsor: Sunnybrook Health Sciences Centre
Recruiting

Evaluation of New Diagnostic Indicator of Subclinical Hypercortisolism

Posted: April 6th, 2021, 2:00pm GMT

Conditions: Adrenal Incidentaloma; Subclinical Hypercortisolism
Intervention: Diagnostic Test: experimental group
Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Recruiting

Quadratus Lumborum Block Versus Thoracic Paravertebral Block

Posted: April 1st, 2021, 2:00pm GMT

Condition: Postoperative Analgesia
Interventions: Combination Product: Ultrasound guided quadratus lumborum block; Combination Product: Ultrasound guided thoracic paravertebral block
Sponsors: National Cancer Institute, Egypt; National Cancer Institute (NCI)
Not yet recruiting

The Physical and Psychologic Effects of Aromatherapy in Cancer Patients During Chemotherapy

Posted: April 1st, 2021, 2:00pm GMT

Conditions: Pain; Heart Rate Variability; Anxiety
Intervention: Other: essential oils
Sponsor: Show Chwan Memorial Hospital
Not yet recruiting

Research on the Effectiveness and Safety of Remote Control of Domestic Surgical Robot System for Urinary Surgery

Posted: March 18th, 2021, 2:00pm GMT

Conditions: Renal Cell Carcinoma; Adrenal Tumor; Nonfunctioning Kidney
Intervention: Device: telesurgery by domestic robot
Sponsor: The Affiliated Hospital of Qingdao University
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, 3:00pm 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
Sponsor: M.D. Anderson Cancer Center
Not yet 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
Not yet recruiting

Expanding Rural Health Cancer Control Capacity

Posted: February 22nd, 2021, 3:00pm GMT

Condition: Cancer
Interventions: Behavioral: Survivorship Patient Navigation Intervention; Behavioral: Telehealth Survivorship Visit Intervention
Sponsors: Debra Friedman; National Cancer Institute (NCI)
Recruiting

Responses to COVID-19 Vaccination in Patients With Cancer

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

Condition: Cancer
Intervention: Diagnostic Test: IgG neutralising antibody titers to S1 and S2 proteins of SARS-COV-2 virus
Sponsor: Hellenic Cooperative Oncology Group
Recruiting

Intraoperative Norepinephrine Versus Fresh Frozen Plasma in Patients Undergoing HIPEC to Reduce Renal Insult

Posted: December 24th, 2020, 3:00pm GMT

Condition: Anesthesia
Interventions: Drug: Norepinephrine; Biological: Fresh frozen plasma
Sponsor: National Cancer Institute, Egypt
Recruiting

RCT Comparing ESPB Solutions in Breast Surgery

Posted: October 27th, 2020, 2:00pm GMT

Condition: Breast Cancer
Interventions: Drug: Liposomal bupivacaine; Drug: Bupivacaine, epinephrine, dexamethasone, and clonidine
Sponsor: Tufts Medical Center
Recruiting

Global Safety and Efficacy Registration Study of Crinecerfont for Congenital Adrenal Hyperplasia

Posted: July 29th, 2020, 2:00pm GMT

Condition: Congenital Adrenal Hyperplasia
Interventions: Drug: Crinecerfont; Drug: Placebo
Sponsor: Neurocrine Biosciences
Recruiting

Natural History Study of Children and Adults With Adrenocortical Cancer (ACC)

Posted: June 25th, 2020, 2:00pm GMT

Conditions: Adrenocortical Carcinoma; Adrenocortical Cancer
Intervention:
Sponsor: National Cancer Institute (NCI)
Recruiting

Patients With ES-SCLC and ECOG PS=2 Receiving Atezolizumab-Carboplatin-Etoposide

Posted: January 9th, 2020, 3:00pm GMT

Condition: SCLC, Extensive Stage
Intervention: Drug: Atezolizumab
Sponsors: AIO-Studien-gGmbH; Hoffmann-La Roche
Recruiting

Biological Effect of Vitamin D in Patients With Urothelial Carcinoma

Posted: December 12th, 2019, 3:00pm GMT

Condition: Urothelial Carcinoma
Intervention: Drug: Vitamin D
Sponsors: Germans Trias i Pujol Hospital; Spanish Clinical Research Network - SCReN; Centro Nacional de Investigaciones Oncologicas CARLOS III; Fundació Institut Germans Trias i Pujol
Recruiting

Stereotactic Magnetic Resonance Guided Radiation Therapy

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

Conditions: Pancreas Cancer; Lung Cancer; Renal Cancer; Adrenal Metastases; Prostate Cancer; Liver Metastases; Oligoprogressive Nodal Metastases; Metachronous Nodal Metastases; Synchronous Nodal Metastases
Intervention: Radiation: MR-guided Linac
Sponsor: Dana-Farber Cancer Institute
Recruiting

ESP Block for Laparoscopic Nephrectomy Surgeries

Posted: September 11th, 2019, 2:00pm GMT

Conditions: Nephrectomy, Anesthesia, Regional, Patient-controlled, Analgesia; Kidney Diseases
Interventions: Drug: Ropivacaine injection; Other: Sham
Sponsors: McMaster University; St. Joseph's Healthcare Hamilton
Recruiting

Biological Response to Brief Psychological Challenge

Posted: September 4th, 2019, 2:00pm GMT

Condition: Acute Inflammatory Response to Psychological Stress
Interventions: Behavioral: Socio-evaluative speech task, then Control; Behavioral: Control, then Socio-evaluative speech task
Sponsors: University of Pittsburgh; National Institute of Mental Health (NIMH)
Recruiting

Dose-Escalation and Efficacy Study of LAE001/Prednisone Plus Afuresertib Patients With m-CRPC

Posted: August 19th, 2019, 2:00pm GMT

Condition: Metastatic Castration-resistant Prostate Cancer
Intervention: Drug: Phase I and Phase II: LAE001/prednisone + afuresertib
Sponsor: Laekna Limited
Recruiting

The Registry of Oncology Outcomes Associated With Testing and Treatment

Posted: July 22nd, 2019, 2:00pm 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)
Sponsor: Taproot Health
Not yet 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

SABR for Renal Tumors

Posted: November 20th, 2018, 3:00pm GMT

Condition: Renal Tumor
Intervention: Radiation: Stereotactic Ablative Radiotherapy
Sponsor: University Health Network, Toronto
Recruiting

Permalink for 'Mitotane With or Without Cisplatin and Etoposide After Surgery in Treating Participants With Stage I-III Adrenocortical Cancer With High Risk of Recurrence (ADIUVO-2)'

Mitotane With or Without Cisplatin and Etoposide After Surgery in Treating Participants With Stage I-III Adrenocortical Cancer With High Risk of Recurrence (ADIUVO-2)

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

Nivolumab Combined With Ipilimumab for Patients With Advanced Rare Genitourinary Tumors

Posted: November 7th, 2017, 3:00pm GMT

Conditions: Genitourinary Cancer; Adrenocortical Carcinoma; Non-urothelial Bladder; Non-urothelial Upper Tract; Penile Cancer; Non-adenocarcinoma Prostate Cancer; Refractory Germ-cell; High Grade Neuroendocrine Carcinoma/Small Cell Carcinoma
Interventions: Drug: Ipilimumab; Drug: Nivolumab
Sponsors: Dana-Farber Cancer Institute; Bristol-Myers Squibb
Recruiting

Propranolol Hydrochloride in Treating Patients With Prostate Cancer Undergoing Surgery

Posted: May 15th, 2017, 2:00pm GMT

Condition: Prostate Carcinoma
Interventions: Other: Laboratory Biomarker Analysis; Drug: Propranolol Hydrochloride; Other: Questionnaire Administration; Other: Survey Administration
Sponsors: Wake Forest University Health Sciences; National Cancer Institute (NCI)
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

Study of Biomarker-Based Treatment of Acute Myeloid Leukemia

Posted: January 9th, 2017, 3:00pm GMT

Condition: Previously Untreated Acute Myeloid Leukemia
Interventions: Biological: Samalizumab (BAML-16-001-S1); Biological: BI 836858 (BAML-16-001-S2); Other: Laboratory Biomarker Analysis; Drug: Daunorubicin (BAML-16-001-S1); Drug: Cytarabine (BAML-16-001-S1); Drug: Azacitidine (BAML-16-001-S2); Drug: AG-221 (BAML-16-001-S3); Drug: Azacitidine (BAML-16-001-S3); Drug: Entospletinib (BAML-16-001-S4); Drug: Azacitidine (BAML-16-001-S4); Drug: Entospletinib (BAML-16-001-S5); Drug: Decitabine (BAML-16-001-S5); Drug: Entospletinib (BAML-16-001-S6); Drug: Daunorubicin (BAML-16-001-S6); Drug: Cytarabine (BAML-16-001-S6); Drug: Pevonedistat (BAML-16-001-S9); Drug: Azacitidine (BAML-16-001-S9); Drug: AG-120 (BAML-16-001-S16); Drug: Azacitidine (BAML-16-001-S16); Drug: Gilteritinib (BAML-16-001-S8); Drug: Decitabine (BAML-16-001-S8); Drug: AZD5153 (BAML-16-001-S10); Drug: Venetoclax (BAML-16-001-S10); Drug: TP-0903 (BAML-16-001-S14); Drug: Decitabine (BAML-16-001-S14)
Sponsor: Beat AML, LLC
Recruiting

Study of Nivolumab Plus Ipilimumab, Ipilimumab or Cabazitaxel in Men With Metastatic Castration-Resistant Prostate Cancer

Posted: December 7th, 2016, 3:00pm GMT

Condition: Prostate Cancer
Interventions: Biological: Nivolumab; Biological: Ipilimumab; Drug: Cabazitaxel; Drug: Prednisone
Sponsor: Bristol-Myers Squibb
Recruiting

Permalink for 'Cabozantinib S-malate in Treating Patients With Metastatic Pheochromocytomas or Paragangliomas That Cannot Be Removed by Surgery'

Cabozantinib S-malate in Treating Patients With Metastatic Pheochromocytomas or Paragangliomas That Cannot Be Removed by Surgery

Posted: November 27th, 2014, 3:00pm GMT

Conditions: Locally Advanced Paraganglioma; Metastatic Adrenal Gland Pheochromocytoma; Metastatic Paraganglioma; Regional Adrenal Gland Pheochromocytoma; Unresectable Adrenal Gland Pheochromocytoma; Unresectable Paraganglioma
Interventions: Drug: Cabozantinib S-malate; Other: Laboratory Biomarker Analysis; Other: Questionnaire Administration
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Recruiting

Adrenal Tumors - Pathogenesis and Therapy

Posted: April 30th, 2008, 2:00pm GMT

Conditions: Adrenal Tumors; Adrenocortical Carcinoma; Cushing Syndrome; Conn Syndrome; Pheochromocytoma
Intervention:
Sponsors: University of Wuerzburg; Deutsche Krebshilfe e.V., Bonn (Germany); German Federal Ministry of Education and Research
Recruiting

German Adrenocortical Carcinoma Registry

Posted: March 29th, 2007, 2:00pm GMT

Condition: Adrenocortical Carcinoma
Intervention:
Sponsors: University of Wuerzburg; Deutsche Krebshilfe e.V., Bonn (Germany)
Recruiting

Diagnosis of Pheochromocytoma

Posted: March 3rd, 2000, 3:00pm GMT

Conditions: Pheochromocytoma; Endocrine Disease; Endocrine Diseases
Interventions: Drug: ([18F]-DOPA); Drug: [68Ga]-DOTATATE; Drug: ([18F]-6F-DA)
Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Recruiting

Clinical Characteristics and Survival Outcomes in Neuroblastoma With Bone Metastasis Based on SEER Database Analysis

Fetched: June 19th, 2021, 5:00am GMT by Bin He

Front Oncol. 2021 Jun 1;11:677023. doi: 10.3389/fonc.2021.677023. eCollection 2021.

ABSTRACT

PURPOSE: Clinical features and survival analysis of neuroblastoma (NB) are well explored. However, clinical research of NB patients with bone metastasis is rarely reported. Thus, the current study was performed to analyze the clinical features, survival outcome, and risk factors in those patients.

MATERIALS AND METHODS: We reviewed the Surveillance, Epidemiology, and End Results (SEER) database to select cases diagnosed with NB with bone metastasis from 2010 to 2016. Overall survival (OS) and cancer-specific survival (CSS) were analyzed through univariate Cox regression analysis. Subsequently, we performed multivariate analysis to determine independent predictors of survival. The Kaplan-Meier method was applied to intuitively show differences in prognostic value between independent risk factors.

RESULTS: We finally identified 393 NB patients with bone metastasis who were selected for survival analysis. Nearly half of the patients (47.3%) were aged >3 years. The adrenal gland was the primary tumor site, accounting for approximately two thirds of cases (66.2%). The 5-year OS and CSS rates of all patients were 62.1% and 64.1%, respectively. The univariate analysis indicated that age, lung metastasis, and tumor size were significantly associated with OS and CSS. Based on the multivariable analysis, age at 2 and 3 years, lung metastasis, and tumor size >10 cm remained significant negative predictors of OS and CSS.

CONCLUSION: For NB patients with bone metastasis, three independent prognostic risk factors (age, lung metastasis, and tumor size) are helpful to clinicians for predicting prognosis and guiding treatment. Reasonable treatment modalities for these patients should be further investigated to prolong survival.

PMID:34141621 | PMC:PMC8203907 | DOI:10.3389/fonc.2021.677023

Clinical value of (18)FDG PET/MRI in muscle-invasive, locally advanced, and metastatic bladder cancer

Fetched: June 19th, 2021, 5:00am GMT by Ali Cahid Civelek

Urol Oncol. 2021 Jun 14:S1078-1439(21)00181-2. doi: 10.1016/j.urolonc.2021.04.024. Online ahead of print.

ABSTRACT

OBJECTIVE: Metastatic bladder cancer is an aggressive disease that can often be difficult to diagnose and stage with conventional cross-sectional imaging. The primary objective of this study was to determine the clinical value of fluorine-18 2-fluoro-2-deoxy-D-glucose (¹⁸F-FDG) PET/MRI for surveillance and restaging of patients with muscle-invasive, locally advanced, and metastatic bladder cancer compared to conventional imaging methods.

MATERIALS AND METHODS: This retrospective study enrolled patients with muscle-invasive, locally advanced and metastatic bladder cancer in a single institute evaluated with ¹⁸F-FDG PET/MRI. All patients also underwent conventional imaging with CT. Additional imaging may also have included ¹⁸F-FDG PET/CT (¹⁸F-FDG PET), or sodium fluoride (NaF) PET/CT in some patients. Images were reviewed by a diagnostic radiologist/nuclear medicine physician. Number of lesions and sites of disease were captured and compared between ¹⁸F-FDG PET/MRI and conventional imaging. Lesions were confirmed by sequential imaging or lesion biopsy. All patients were followed for survival.

RESULTS: Fifteen patients (4 for surveillance; 11 for restaging) underwent 34 ¹⁸F-FDG PET/MRI scans. Each patient received a corresponding conventional CT around the time of the ¹⁸F-FDG PET/MRI (median 6 days). The 15 patients (11 male; 4 female) had a median age of 61.5 years (range 37-73) and histologies of urothelial carcinoma (n = 13) and small-cell carcinoma of the bladder (n = 2) diagnosed as stage 4 (n = 13), stage 3 (n = 1), or stage 2 (n = 1). ¹⁸F-FDG PET/MRI detected 82 metastatic malignant lesions involving lymph nodes (n = 22), liver (n = 10), lung (n = 34), soft tissue (n = 12), adrenal glands (n = 1), prostate (n = 1), and bone (n = 2) with a resultant advantage of 36% for lesion visibility in comparison with CT. Serial imaging or biopsy confirmed these lesions as malignant.

CONCLUSION: ¹⁸F-FDG PET/MRI can detect metastatic lesions which cannot be identified on conventional CT, and this can allow for better treatment planning and improved disease monitoring during therapy.

PMID:34140245 | DOI:10.1016/j.urolonc.2021.04.024

Isolated adrenocorticotropin deficiency induced by pembrolizumab for hypopharyngeal cancer: A case report

Fetched: June 18th, 2021, 5:00am GMT by Koichiro Yamamoto

Clin Case Rep. 2021 Jun 10;9(6):e04305. doi: 10.1002/ccr3.4305. eCollection 2021 Jun.

ABSTRACT

We report a case of isolated adrenocorticotropin deficiency caused by pembrolizumab. This condition can be fatal, but its rarity causes under-recognition. Oncologists should pay attention to adrenal insufficiency due to pembrolizumab.

PMID:34136239 | PMC:PMC8190675 | DOI:10.1002/ccr3.4305

Interactive regulation of laryngeal cancer and neuroscience

Fetched: June 17th, 2021, 5:00am GMT by Yunjing Hou

Biochim Biophys Acta Rev Cancer. 2021 Jun 12:188580. doi: 10.1016/j.bbcan.2021.188580. Online ahead of print.

ABSTRACT

Nerve fibres are distributed throughout the body along with blood and lymphatic vessels. The intrinsic morphological characteristics of nerves and the general characteristics of secretions in the tumour microenvironment provide a solid theoretical basis for exploring how neuronal tissue can influence the progression of laryngeal cancer (LC). The central nervous system (CNS) and the peripheral nervous system (PNS) jointly control many aspects of cancer and have attracted widespread attention in the study of the progression, invasion and metastasis of tumour tissue banks. Stress activates the neuroendocrine response of the human hypothalamus-pituitary-adrenal (HPA) axis. LC cells induce nerve growth in the microenvironment by releasing neurotrophic factors (NTFs), and they can also stimulate neurite formation by secreting axons and axon guides. Conversely, nerve endings secrete factors that attract LC cells; this is known as perineural invasion (PNI) and promotes the progression of the associated cancer. In this paper, we summarize the systematic understanding of the role of neuroregulation in the LC tumour microenvironment (TME) and ways in which the TME accelerates nerve growth, which is closely related to the occurrence of LC.

PMID:34129916 | DOI:10.1016/j.bbcan.2021.188580

Permalink for 'Adrenalectomy During Radical Nephrectomy- Incidence and Oncologic Outcomes from the Canadian Kidney Cancer Information System (CKCis) -A Modern Era, Nationwide, Multicenter Cohort'

Adrenalectomy During Radical Nephrectomy- Incidence and Oncologic Outcomes from the Canadian Kidney Cancer Information System (CKCis) -A Modern Era, Nationwide, Multicenter Cohort

Fetched: June 17th, 2021, 5:00am GMT by Arnon Lavi

Urology. 2021 Jun 12:S0090-4295(21)00482-9. doi: 10.1016/j.urology.2021.05.053. Online ahead of print.

ABSTRACT

OBJECTIVE: To characterize proportion of patients receiving adrenalectomy, adrenal involvement prevalence and oncologic outcomes of routine adrenalectomy in contemporary practice. Ipsilateral adrenalectomy was once standard during radical nephrectomy. However, benefit of routine adrenalectomy has been questioned because adrenal involvement of renal cell carcinoma (RCC) is low.

METHODS: All patients receiving radical nephrectomy in the Canadian Kidney Cancer information system (CKCis), a collaborative prospective cohort populated by 14 major Canadian centers, between January 2011 to February 2020 were included. Patients were excluded if they had non-RCC histology, multiple tumors, contralateral tumors, metastatic disease or previous history of RCC. Patient demographic, clinical, and surgical information were summarized and compared. Cox-proportional hazards was used for multivariable analysis.

RESULTS: During study period, 2759 patients received radical nephrectomy, of these, 831(30.1%) had concomitant adrenalectomy. Pathological adrenal involvement was identified in 102 (3.7%overall; 12.3%of adrenalectomy). Median follow-up was 21.6months (Interquartile range 7.0-46.5). Patients with adrenalectomy had higher venous tumor thrombus (30.3% vs. 9.6%; p<0.0001), higher T stage (71.1% vs. 43.4% pT3/4; p<0.0001), lymph node metastases (17.6% vs. 10.7%; p=0.0035), Fuhrman grades (71.4% of Fuhrman grades 3/4 vs. 56.2%; p<0.0001) and increased proportion of clear cell histology (79.3% vs. 74.5%; p=0.0074) compared to the no adrenalectomy group. Adrenalectomy patients had higher risk of recurrence (HR 1.23; 95%CI 1.04-1.47; P=0.019) and no difference in survival (HR 1.09, 95% CI 0.86-1.38, p=0.48).

CONCLUSION: Adrenalectomy is not associated with better oncological outcome of recurrence/survival. Adrenalectomy should be reserved for patients with radiographic adrenal involvement and/or intra-operative adrenal involvement.

PMID:34129893 | DOI:10.1016/j.urology.2021.05.053

An unexpected intracerebral lesion - case report of a superinfected aspergillosis mimicking a brain metastasis

Fetched: June 17th, 2021, 5:00am GMT by Basil Erwin Grüter

BMC Infect Dis. 2021 Jun 7;21(1):537. doi: 10.1186/s12879-021-06176-7.

ABSTRACT

BACKGROUND: Invasive aspergillosis of the central nervous system is a rare but increasingly prevalent disease. We present the unusual case of an immunosuppressed patient suffering from unexpected superinfected invasive aspergillosis with cerebral, pulmonal, and adrenal manifestations, mimicking a metastasized bronchial carcinoma. This report reveals the importance of including aspergillosis in the differential diagnosis of a cerebral mass lesion in the light of unspecific clinical findings.

CASE PRESENTATION: A 58-year-old immunocompromised female presented to our emergency department with a single tonic-clonic seizure. Imaging showed a ring enhancing cerebral mass with perifocal edema and evidence of two smaller additional hemorrhagic cerebral lesions. In the setting of a mass lesion in the lung, and additional nodular lesions in the left adrenal gland the diagnosis of a metastasized bronchus carcinoma was suspected and the cerebral mass resected. However, histology did not reveal any evidence for a neoplastic lesion but septate hyphae consistent with aspergillus instead and microbiological cultures confirmed concomitant staphylococcal infection.

CONCLUSIONS: A high index of suspicion for aspergillus infection should be maintained in the setting of immunosuppression. Clinical and radiological findings are often unspecific and even misleading. Definite confirmation usually relies on tissue diagnosis with histochemical stains. Surgical resection is crucial for establishing the diagnosis and guiding therapy with targeted antifungal medications.

PMID:34098877 | PMC:PMC8186049 | DOI:10.1186/s12879-021-06176-7

Androgen receptor signalling inhibitors: post-chemotherapy, pre-chemotherapy and now in castration sensitive prostate cancer

Fetched: June 16th, 2021, 5:00am GMT by Nicholas Mitsiades

Endocr Relat Cancer. 2021 Jun 1:ERC-21-0098.R1. doi: 10.1530/ERC-21-0098. Online ahead of print.

ABSTRACT

Based on pioneering work by Huggins, Hodges and others, hormonal therapies have been established as an effective approach for advanced prostate cancer (PC) for the past 8 decades. However, it quickly became evident that androgen deprivation therapy (ADT) via surgical or medical castration accomplishes inadequate inhibition of the androgen receptor (AR) axis, with clinical resistance inevitably emerging due to adrenal and intratumoral sources of androgens and other mechanisms. Early efforts to augment ADT by adding adrenal-targeting agents (aminoglutethimide, ketoconazole) or AR antagonists (flutamide, bicalutamide, nilutamide, cyproterone) failed to achieve overall survival (OS) benefits, although they did exhibit some evidence of limited clinical activity. More recently, four new Androgen Receptor Signalling Inhibitors (ARSIs) successfully entered clinical practice. Specifically, the CYP17 inhibitor abiraterone acetate and the 2nd generation AR antagonists (enzalutamide, apalutamide and darolutamide) achieved OS benefits for PC patients, confirmed the importance of reactivated AR signaling in castration-resistant PC and validated important concepts that had been proposed in the field several decades ago but had remained so far unproven, including adrenal-targeted therapy and combined androgen blockade. The past decade has seen steady advances towards more comprehensive AR axis targeting. Now the question is raised whether we have accomplished the maximum AR axis inhibition possible or there is still room for improvement. This review, marking the 80-year anniversary of ADT and 10-year anniversary of successful ARSIs, examines their current clinical use and discusses future directions, in particular combination regimens, to maximize their efficacy, delay emergence of resistance and improve patient outcomes.

PMID:34128827 | DOI:10.1530/ERC-21-0098

Interventricular septum mass presenting as a late acute coronary syndrome with ST-segment elevation: a case report

Fetched: June 15th, 2021, 5:00am GMT by Lucas Coroyer

Eur Heart J Case Rep. 2021 May 12;5(5):ytab164. doi: 10.1093/ehjcr/ytab164. eCollection 2021 May.

ABSTRACT

BACKGROUND: Intracardiac masses are relatively rare but the diagnosis can be challenging for the cardiologist and the clinical presentation can be misleading. While most of the cardiac masses are benign, malignant masses are mostly metastatic tumours.

CASE SUMMARY: An 81-year-old man was admitted to the cardiology department for congestive heart failure with the complaint of recent dyspnoea. The initial electrocardiogram was suggestive of a late presentation of an anterior myocardial infarction. Blood test showed mild and stable elevation of troponin and brain natriuretic peptide. Doppler-echocardiography revealed an interventricular septal thickening. Contrast echocardiography revealed a mass with a possibly necrotic centre and peripheral hypervascularization. Cardiac computed tomography (CT) confirmed the existence of a cardiac tumour with a hypodense centre and also revealed the presence of a large tumour of the lung's left lower lobe with multiple enlarged lymph nodes associated with possible left adrenal gland metastasis. Computed tomography-guided percutaneous biopsy of the pulmonary mass demonstrated a squamous cell lung cancer which was likely the primary cancer. The patient was discharged home waiting for chemotherapy to start but died a few days later at home of an unknown cause.

DISCUSSION: Diagnosis of intracardiac mass is difficult, often requiring multiple imaging modalities. Contrast-enhanced echocardiography may help early diagnosis and can be easily implemented with other imaging modalities such as cardiac magnetic resonance imaging or CT.

PMID:34124566 | PMC:PMC8189305 | DOI:10.1093/ehjcr/ytab164

Kaposi sarcoma of the adrenal gland: A report of two cases with a review of the literature

Fetched: June 15th, 2021, 5:00am GMT by Sabrine Derqaoui

J Cancer Res Ther. 2021 Apr-Jun;17(2):606-608. doi: 10.4103/jcrt.JCRT_670_20.

ABSTRACT

Kaposi sarcoma (KS) is a low-grade vascular neoplasm commonly involving mucocutaneous sites, while adrenal gland involvement is exceptional. The anaplastic variant is a rare entity characterized by marked cellular pleomorphism, increased mitosis, worse prognosis, and an increased metastatic potential. The diagnosis remains on histology and immunohistochemistry. We describe two cases of primary adrenal KS to report on this exceptional presentation of KS: the first case is a 67-year-old female with anaplastic KS wit fatal outcome. The second case is a 56-year-old male who presented a classic KS of the adrenal gland. Until now, no standard efficient treatment regimens have been clearly identified. There is a need for a further understanding of anaplastic KS's biology, and collecting a sizable patient cohort remains essential to review treatment outcome.

PMID:34121721 | DOI:10.4103/jcrt.JCRT_670_20

Comparison of MRI features in lipid-rich and lipid-poor adrenal adenomas using subjective and quantitative analysis

Fetched: June 15th, 2021, 5:00am GMT by Wendy Tu

Abdom Radiol (NY). 2021 Jun 12. doi: 10.1007/s00261-021-03161-1. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare MR-imaging features in benign lipid-rich and lipid-poor adrenal adenomas.

MATERIALS AND METHODS: With institutional review board approval, we compared 23 consecutive lipid-poor adenomas (chemical shift [CS] signal intensity [SI] index < 16.5%) imaged with MRI to 29 consecutive lipid-rich adenomas (CS-SI index ≥ 16.5%) imaged during the same time period. A blinded radiologist measured T2-weighted (T2W) SI ratio (adrenal adenoma/psoas muscle), dynamic enhancement wash-in (WI) and wash-out (WO) indices, and T2W texture features. Two blinded Radiologists (R1/R2) assessed T2W-SI (relative to renal cortex) and T2W heterogeneity (using 5-Point Likert scales). Comparisons were performed between groups using independent t tests and Chi-square with Holm-Bonferroni correction.

RESULTS: There was no difference in age or gender between groups (p = 0.594, 0.051 respectively). Subjectively, all lipid-rich and lipid-poor adenomas were rated hypointense or isointense compared to renal cortex and T2W-SI did not differ between groups (p = 0.129, 0.124 for R1, R2). Agreement was substantial (Kappa = 0.67). There was no difference in T2W SI ratio (1.8 ± 0.9 [0.5-4.3] lipid rich versus 2.2 ± 1.0 [0.6-4.3] lipid poor, p = 0.139). Enhancement WI and WO did not differ comparing lipid-rich and lipid-poor adenomas (p = 0.759, 0.422 respectively). There was no difference comparing lipid-rich and lipid-poor adenomas T2W heterogeneity judged subjectively (p = 0.695, 0.139 for R1, R2; Kappa = 0.19) or by texture analysis (entropy, kurtosis, skewness; p = 0.134-0.191) with all adenomas except for one rated as mostly or completely homogeneous.

CONCLUSIONS: There is no difference in T2W signal intensity, enhancement pattern or T2W heterogeneity judged subjectively or by quantitative texture analysis comparing lipid-poor and lipid-rich adrenal adenomas.

PMID:34120206 | DOI:10.1007/s00261-021-03161-1

Incidentally discovered myelolipomatous adrenal adenomas, including six cases presenting with hypercortisolism

Fetched: June 15th, 2021, 5:00am GMT by Katrina Collins

Pathol Res Pract. 2021 Jun 6;224:153508. doi: 10.1016/j.prp.2021.153508. Online ahead of print.

ABSTRACT

Most adrenal incidentalomas are non-functioning adenomas that require no treatment. The presence of a myelolipomatous component of adrenal incidentalomas is a rare, but well-known occurrence in both hyperplastic and neoplastic lesions of the adrenal cortex. Although the improvements in abdominal imaging have increased identification of myelolipomatous adrenal cortical adenomas radiologically, due to the rarity of this lesion, the clinical pathological features of these lesions are unclear and can sometimes cause diagnostic difficulty. Eleven patients had surgeries at The University of Texas MD Anderson Cancer Center. Four additional cases were provided from an external collaborator. Of the 15 cases, there were 5 male and 10 female patients, with a median age of 52 years (mean 54 years, range 28-84 years). Clinical presentation included adrenal incidentaloma (n = 9), Cushing syndrome (n = 4, including 1 as a part of Carney complex), and subclinical Cushing syndrome (n = 2, including 1 with bilateral macronodular adrenal hyperplasia). In this study, we present the clinicopathologic features of fifteen myelolipomatous adrenal adenomas, the largest series published thus far.

PMID:34119816 | DOI:10.1016/j.prp.2021.153508

Permalink for 'Adenomatoid tumor of the adrenal gland: Clinicopathologic characteristics and differential diagnosis on two tumors of exceptional adrenal location'

Adenomatoid tumor of the adrenal gland: Clinicopathologic characteristics and differential diagnosis on two tumors of exceptional adrenal location

Fetched: June 15th, 2021, 5:00am GMT by Sophie Neyrand

Ann Pathol. 2021 Jun 9:S0242-6498(21)00085-7. doi: 10.1016/j.annpat.2021.03.011. Online ahead of print.

ABSTRACT

Adenomatoid tumors are benign tumors from mesothelial origin, usually occurring in the genital tract. Extragenital locations, especially in the adrenal gland are extremely rare. Here we are reporting two cases of a 28-year-old and 50-year-old men with an adenomatoid tumor of the right adrenal gland. Usual morphological aspects join scattered and microcystic pattern with epithelioid or signet-ring cells. According to the morphological features, main differential diagnoses are adenocarcinoma metastasis, vascular tumors or mesotheliomas. Immunohistochemistry provides precious help to confirm the mesothelial origin thanks to positivity of epithelial markers (CK7, AE1-AE3, CK5/6) coupled to mesothelial markers (D2-40, Calretinin, WT1). On the other hand, there is no loss of BAP1 by immunohistochemistry and usually a surexpression of P16. Adrenal gland adenomatoid tumor is a benign tumor, which can be promoted by iatrogenous or constitutive immunodepression.

PMID:34119370 | DOI:10.1016/j.annpat.2021.03.011

Multiple endocrine neoplasia 2A with RET mutation p.Cys611Tyr: A case report

Fetched: June 12th, 2021, 5:00am GMT by Yan Li

Medicine (Baltimore). 2021 Jun 4;100(22):e26230. doi: 10.1097/MD.0000000000026230.

ABSTRACT

RATIONALE: Multiple endocrine neoplasia 2A (MEN2A) is a rare autosomal-dominant genetic syndrome, frequently misdiagnosed or neglected clinically, resulting in delayed therapy to patients.

PATIENT CONCERNS: A 47-year-old Chinese male patient underwent laparoscopic right adrenal tumorectomy, and postoperative pathology confirmed the tumor as pheochromocytoma (PHEO). He was readmitted to the department of endocrinology and metabolism due to constant increase in carcinoembryonic antigen (CEA) at 5 months after the operation.

DIAGNOSIS: The patient was confirmed with medullary thyroid carcinoma (MTC), multiple neck lymph node metastasis, and pituitary microadenoma. The p.Cys611Tyr (c.1832G>A, C611Y) mutation was detected. Therefore, he was diagnosed with MEN2A.

INTERVENTIONS: He underwent total thyroidectomy. The gene-sequencing analysis of his family was conducted, and the C611Y mutation was detected in his daughter.

OUTCOMES: The level of carcinoembryonic antigen decreased significantly after thyroidectomy in this patient. Long-term follow-up management was conducted. Elevated serum calcitonin and bilateral thyroid nodules were found in his 13-year-old daughter. Thus, MEN2A was highly suspected and she was suggested to undergo total thyroidectomy.

CONCLUSION: Patients with MEN2A should be screened regularly and managed by a multidisciplinary team.

PMID:34087905 | PMC:PMC8183697 | DOI:10.1097/MD.0000000000026230

Hypertensive Heartbreak

Fetched: June 11th, 2021, 5:00am GMT by Emily S Lau

N Engl J Med. 2021 May 27;384(21):e80. doi: 10.1056/NEJMimc2031595.

NO ABSTRACT

PMID:34042392 | DOI:10.1056/NEJMimc2031595

Effects of Sorafenib, a Tyrosin Kinase Inhibitor, on Adrenocortical Cancer

Fetched: June 11th, 2021, 5:00am GMT by Lidia Cerquetti

Front Endocrinol (Lausanne). 2021 May 24;12:667798. doi: 10.3389/fendo.2021.667798. eCollection 2021.

ABSTRACT

The lack of an effective medical treatment for adrenocortical carcinoma (ACC) has prompted the search for better treatment protocols for ACC neoplasms. Sorafenib, a tyrosine kinase inhibitor has exhibited effectiveness in the treatment of different human tumors. Therefore, the aim of this study was to understand the mechanism through which sorafenib acts on ACC, especially since treatment with sorafenib alone is sometimes unable to induce a long-lasting antiproliferative effect in this tumor type. The effects of sorafenib were tested on the ACC cell line H295R by evaluating cell viability, apoptosis and VEGF receptor signaling which was assessed by analyzing VE-cadherin and β-catenin complex formation. We also tested sorafenib on an in vitro 3D cell culture model using the same cell line. Apoptosis was observed after sorafenib treatment, and coimmunoprecipitation data suggested that the drug prevents formation VEGFR-VE-cadherin and β-catenin proteins complex. These results were confirmed both by ultrastructural analysis and by a 3D model where we observed a disaggregation of spheres into single cells, which is a crucial event that represents the first step of metastasis. Our findings suggest that although sorafenib induces apoptotic cell death a small portion of cells survive the treatment and have characteristics of a malignancy. Based on our data we recommend against the use of sorafenib in patients with ACC.

PMID:34108938 | PMC:PMC8183165 | DOI:10.3389/fendo.2021.667798

Permalink for 'A novel supplement with yeast β-glucan, prebiotic, minerals and Silybum marianum synergistically modulates metabolic and inflammatory pathways and improves steatosis in obese mice'

A novel supplement with yeast β-glucan, prebiotic, minerals and Silybum marianum synergistically modulates metabolic and inflammatory pathways and improves steatosis in obese mice

Fetched: June 11th, 2021, 5:00am GMT by Victor Abou Nehmi

J Integr Med. 2021 May 28:S2095-4964(21)00059-5. doi: 10.1016/j.joim.2021.05.002. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the synergic effects of a novel oral supplement formulation, containing prebiotics, yeast β-glucans, minerals and silymarin (Silybum marianum), on lipid and glycidic metabolism, inflammatory and mitochondrial proteins of the liver, in control and high-fat diet-induced obese mice.

METHODS: After an acclimation period, 32 male C57BL/6 mice were divided into the following groups: nonfat diet (NFD) vehicle, NFD supplemented, high-fat diet (HFD) vehicle and HFD supplemented. The vehicle and experimental formulation were administered orally by gavage once a day during the last four weeks of the diet (28 consecutive days). We then evaluated energy homeostasis, inflammation, and mitochondrial protein expression in these groups of mice.

RESULTS: After four weeks of supplementation, study groups experienced reduced glycemia, dyslipidemia, fat, and hepatic fibrosis levels. Additionally, proliferator-activated receptor-α, AMP-activated protein kinase-1α, peroxisome proliferator-activated receptor γ co-activator -1α, and mitochondrial transcription factor A expression levels were augmented; however, levels of inhibitor of nuclear factor-κB kinase subunit α and p65 nuclear factor-κB expression, and oxidative markers were reduced. Notably, the cortisol/C-reactive protein ratio, a well-characterized marker of the hypothalamic-pituitary-adrenal axis immune interface status, was found to be modulated by the supplement.

CONCLUSION: We discovered that the novel supplement was able to modify different antioxidant, metabolic and inflammatory pathways, improving the energy homeostasis and inflammatory status, and consequently alleviated hepatic steatosis.

PMID:34108131 | DOI:10.1016/j.joim.2021.05.002

Asian Conference on Tumor Ablation Guidelines for Adrenal Tumor Ablation

Fetched: June 11th, 2021, 5:00am GMT by Byung Kwan Park

Endocrinol Metab (Seoul). 2021 Jun 1. doi: 10.3803/EnM.2021.1008. Online ahead of print.

ABSTRACT

Thermal ablation is a good alternative treatment in patients who are unable to undergo adrenalectomy. Even though the Asian Conference on Tumor Ablation (ACTA) has been held for many years, adrenal ablation guidelines have not been established. No guidelines for adrenal ablation are established in American and European countries, either. The aim of this review was to introduce the first version of ACTA guidelines for adrenal tumor ablation.

PMID:34107604 | DOI:10.3803/EnM.2021.1008

The Impact of COVID-19 Disease on Urology Practice

Fetched: June 10th, 2021, 5:00am GMT by Mohamad Moussa

Surg J (N Y). 2021 Jun 3;7(2):e83-e91. doi: 10.1055/s-0041-1725155. eCollection 2021 Apr.

ABSTRACT

The diagnosis and timely treatment of cancer patients should not be compromised during an infectious disease pandemic. The pandemic of coronavirus disease 2019 (COVID-19) has serious implications on urology practice and raises particular questions for urologists about the management of different conditions. It was recommended to cancel most of the elective urological surgeries. Urological cancers surgeries that should be prioritized are radical cystectomy for selective tumors, orchiectomy for suspected testicular tumors, nephrectomy for c T3 + , nephroureterectomy for high-grade disease, and radical adrenalectomy for tumors >6 cm or adrenal carcinoma. Most prostatectomies can be delayed without compromising the survival rate of patients. Urological emergencies should be treated adequately even during this pandemic. There is a potential risk of coronavirus diffusion during minimally invasive procedures performed. It is crucial to use specific precautions when urologists performed those type of surgeries. It was also recommended to suspend the kidney transplantation program during the COVID-19 pandemic except for specific cases. In this review, we discussed the triage of urological surgeries, the risk of minimally invasive urological procedure, the kidney transplantation challenges, the systemic therapies, intravesical instillation of Bacillus Calmette-Guérin (BCG), endourology, teleconferencing, and telemedicine application in urology during the COVID-19 pandemic.

PMID:34104720 | PMC:PMC8175122 | DOI:10.1055/s-0041-1725155

Clinical Indicators for Long-Term Survival with Immune Checkpoint Therapy in Advanced Hepatocellular Carcinoma

Fetched: June 10th, 2021, 5:00am GMT by Cecilia Monge

J Hepatocell Carcinoma. 2021 May 31;8:507-512. doi: 10.2147/JHC.S311496. eCollection 2021.

ABSTRACT

INTRODUCTION: Patients with advanced hepatocellular carcinoma have a dismal prognosis; only a subset of patients with advanced HCC will benefit from treatment with immunotherapy. We searched for clinical characteristics predicting exceptional long-term survival in HCC patients treated with immune checkpoint inhibitors.

METHODS: We compared clinical characteristics of 59 patients with advanced hepatocellular carcinoma treated with immunotherapy with and without locoregional therapy between 2013-2019. We compared patients who lived less than 12 months with patients who lived more than 3 years. Traits of short-term (31 patients) and long-term (5 patients) survivors were compared. Patients who died between 12 months and 3 years of starting treatment on protocol were not included in the analysis.

RESULTS: Two out of five patients (40%) in the long-term survival group had a partial response (PR) or a complete response (CR) per the modified Response Evaluation Criteria in Solid Tumors (mRECIST), while, of the 31 patients in the short-term survival group, only 2 (6.5%) had a CR or PR. Two of the 5 patients with a long-term survival had immune-related adverse events grade 3 or 4 (IrAEs-3/4). None of the patients in the short-term survival group had IrAEs-3/4. The patients, who presented with IrAEs-3/4, which included colitis and adrenal insufficiency, continued to have a response off treatment. The median overall survival (OS) was 11.8 months (95% CI: 7.8-15.4 months), with a 12-month OS of 46.6% (95% CI: 33.4-58.8%) and a 3-year OS of 12.5% (95% CI: 5.0-23.7%).

CONCLUSION: We found a possible association between immune-related adverse events grade 3 and 4 and long-term survival in patients with advanced HCC. The cases in our analysis represent extraordinary defiance of the usual predicted dismal course of advanced HCC.

PMID:34104639 | PMC:PMC8178695 | DOI:10.2147/JHC.S311496

An unusual case of ectopic thyroid tissue in an adrenal gland presenting as a cyst

Fetched: June 9th, 2021, 5:00am GMT by Shreya Bramhe

Indian J Cancer. 2021 Apr-Jun;58(2):294-295. doi: 10.4103/ijc.IJC_181_20.

NO ABSTRACT

PMID:34100416 | DOI:10.4103/ijc.IJC_181_20

A Case report: Co-occurrence of IMAGe syndrome and Rhabdomyosarcoma

Fetched: June 9th, 2021, 5:00am GMT by Maria Bolomiti

Cancer Genet. 2021 May 26;256-257:100-105. doi: 10.1016/j.cancergen.2021.05.006. Online ahead of print.

ABSTRACT

IMAGe syndrome is a rare congenital disorder, presenting with intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita and genital anomalies (in males). So far only 17 individuals have been diagnosed molecularly with IMAGe syndrome, this patient is the first case of an individual diagnosed with IMAGe and concurrent rhabdomyosarcoma. The patient was born at 30 weeks' gestation and received treatment for hyponatremia and hyperkalemia. At 4 9/12 years of age the patient showed a painless, non-mobile mass on the left thigh. In the biopsy performed a sarcoma weave with solid, nest-like growth, with characteristics of rhabdomyosarcoma was identified. The family history and physical examination indicated IMAGe syndrome so genetic testing was requested. A whole exome sequencing procedure with use of SureSelectXT Human ALL Exon V7, confirmed a single nucleotide variant NM_000076.2(CDKN1C):c.820G>A (p.Asp274Asn); identifying a missense mutation in the imprinted gene CDKN1C associated with IMAGe syndrome. Although tumours associated with CDKN1C are rare, deregulation of imprinted genes is increasingly being recognised as a mechanism of tumorigenesis in cancer; chromosomal region 11p15.5 contains a cluster of imprinted genes. This same region is the most consistent site of allele loss in rhabdomyosarcoma and is the same region altered in both IMAGe and Beckwith-Wiedemann syndrome. Molecular studies have found genetic changes in the 11p15 region in a variety of embryonal tumours like Wilms tumours which are commonly developed in Beckwith-Wiedemann syndrome and embryonal rhabdomyosarcoma. Through this case we aim to present the possibility of oncogenesis in patients with IMAGe syndrome, specifically rhabdomyosarcoma.

PMID:34098225 | DOI:10.1016/j.cancergen.2021.05.006

Measuring steroids from dried blood spots using tandem mass spectrometry to diagnose congenital adrenal hyperplasia

Fetched: June 9th, 2021, 5:00am GMT by Deema O Qasrawi

Clin Chim Acta. 2021 Jun 4:S0009-8981(21)00203-5. doi: 10.1016/j.cca.2021.06.005. Online ahead of print.

ABSTRACT

BACKGROUND: Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders that occur due to defects in the steroidogenesis pathway. Approximately 90% of CAH cases can be diagnosed by the measurement of serum 17-hydroxyprogesterone alone. However, the quantification of six additional steroids could significantly improve CAH laboratory diagnosis. Using dried blood spot (DBS) as specimen of choice can further improve patient care due to the small sample volume required for CAH diagnosis in neonates.

METHODS: An optimized DBS sample preparation method was employed for steroids quantification without the need of derivatization. A LC-MS/MS assay was developed and optimized using a reverse phase-ultra high-pressure liquid chromatography (RP-UHPLC) system combined with triple quadrupole mass spectrometry using positive electrospray ionization mode.

RESULTS: The assay was validated according to CLSI analytical guidelines, including lower limit of quantification (LLOQ), linearity, precision, accuracy, carryover, and method comparison. The analytical measuring range of the method for all steroids was 2.5, 5, or 10 ng/ml to 250 ng/ml in DBS, r² ≥0.995. The LLOQ, intra-day and inter-day precision were 0.11-1.8 ng/ml, 1.2-6.4 ng/ml, 1.8-11.5 %, and 5.3-13.8%, respectively.

CONCLUSIONS: Our LC-MS/MS assay simultaneously detects 7 steroids for the diagnosis of CAH and can be readily implemented in clinical laboratories to provide superior analytical performance over traditional immunoassays.

PMID:34097883 | DOI:10.1016/j.cca.2021.06.005

Adrenal Rests in the Uro-genital Tract of an Adult Population

Fetched: June 8th, 2021, 5:00am GMT by Enrico Costantino Falco

Endocr Pathol. 2021 Jun 7. doi: 10.1007/s12022-021-09685-y. Online ahead of print.

ABSTRACT

Ectopic adrenal rests are a rare condition which can be found in various sites, generally in the retroperitoneum or pelvis along the path of gonadal descent. Their real prevalence is unknown. Males are more commonly affected, at least in the pediatric age. Adrenal rests are usually clinically silent and incidentally found in surgical samples, mostly in the pediatric population, and rarely in adults. With the aim of increasing knowledge and estimating the prevalence of ectopic adrenocortical tissue in the adult population, 44 adrenal rests in the urogenital tract of 40 adults are described. These represent approximately 0.07% of the total number of urogenital and gynecological surgeries performed in the 22 considered years. Adrenal rests were identified in the spermatic cord (10 males) and in paraovarian, parasalpingeal, or infundibulopelvic ligament locations (30 females). All but one was incidental findings. One case regarded an adrenocortical carcinoma arisen in adrenal rests. A literature review of adrenal ectopia in the urogenital tract of adults identified 57 reported cases from 53 patients, with similar clinicopathological features as those of our series, with the exception of a lower incidence of parasalpingeal locations. Despite their limited clinical implications, awareness of ectopic adrenal rests is essential also in adults for at least two reasons: (a) to correctly identify sources of adrenocortical hormone production in case of adrenal insufficiency or hormonal imbalance and (b) to avoid misinterpretations in the diagnostic workup of renal cell carcinoma, adrenocortical tumors, and rare gonadal neoplasms, including Sertoli/Leydig cell tumors.

PMID:34095993 | DOI:10.1007/s12022-021-09685-y

19-hydroxy Steroids in the Aromatase Reaction: Review on Expression and Potential Functions

Fetched: June 8th, 2021, 5:00am GMT by Tatjana Abaffy

J Endocr Soc. 2021 Mar 23;5(7):bvab050. doi: 10.1210/jendso/bvab050. eCollection 2021 Jul 1.

ABSTRACT

Scientific evidence related to the aromatase reaction in various biological processes spanning from mid-1960 to today is abundant; however, as our analytical sensitivity increases, a new look at the old chemical reaction is necessary. Here, we review an irreversible aromatase reaction from the substrate androstenedione. It proceeds in 3 consecutive steps. In the first 2 steps, 19-hydroxy steroids are produced. In the third step, estrone is produced. They can dissociate from the enzyme complex and either accumulate in tissues or enter the blood. In this review, we want to highlight the potential importance of these 19-hydroxy steroids in various physiological and pathological conditions. We focus primarily on 19-hydroxy steroids, and in particular on the 19-hydroxyandrostenedione produced by the incomplete aromatase reaction. Using a PubMed database and the search term "aromatase reaction," 19-hydroxylation of androgens and steroid measurements, we detail the chemistry of the aromatase reaction and list previous and current methods used to measure 19-hydroxy steroids. We present evidence of the existence of 19-hydroxy steroids in brain tissue, ovaries, testes, adrenal glands, prostate cancer, as well as during pregnancy and parturition and in Cushing's disease. Based on the available literature, a potential involvement of 19-hydroxy steroids in the brain differentiation process, sperm motility, ovarian function, and hypertension is suggested and warrants future research. We hope that with the advancement of highly specific and sensitive analytical methods, future research into 19-hydroxy steroids will be encouraged, as much remains to be learned and discovered.

PMID:34095690 | PMC:PMC8169043 | DOI:10.1210/jendso/bvab050

The Vanishing Adrenal Glands: A Transient Regression of Adrenal Lymphoma After a Single Dose of 1 mg Dexamethasone

Fetched: June 8th, 2021, 5:00am GMT by Shamaila Zaman

AACE Clin Case Rep. 2020 Dec 28;7(2):109-112. doi: 10.1016/j.aace.2020.11.022. eCollection 2021 Mar-Apr.

ABSTRACT

OBJECTIVE: Dexamethasone is a known treatment for lymphoma, but the potency and rapidity of its effect have not been recognized. We present a case of bilateral adrenal lymphoma that significantly reduced in size after a single dose of dexamethasone.

METHODS: We present the clinical course and investigations, including adrenocorticotropic hormone, cortisol, short synacthen test, computed tomography (CT), and adrenal biopsy results.

RESULTS: A 52-year-old man had a fall and was incidentally found to have bilateral adrenal masses (left, 6 cm; right, 5 cm) on CT. His adrenal function tests included plasma metanephrines (normetanephrine, 830 pmol/L [normal, <1180]; metanephrine, <100 pmol/L [<510]; 3-methoxytyramine, <100 pmol/L [<180]); aldosterone, 270 pmol/L( 90-700); and random cortisol, 230 nmol/L (160-550). An overnight dexamethasone suppression test with 1 mg of dexamethasone showed cortisol of <28 nmol/L (0-50). A repeat CT scan 8 days thereafter showed adrenal masses of 4.5 and 3.5 cm on the left and right, respectively. He had a follow-up CT scan 3 months later that showed adrenal lesions measuring 8 cm (left) and 9 cm (right). He subsequently presented with fatigue and dizziness. Morning cortisol of 201 nmol/L (160-550) with adrenocorticotropic hormone of 216 ng/L (10-30) indicated primary adrenal insufficiency. Mineralocorticoid and glucocorticoid replacement therapy commenced. An adrenal biopsy showed abnormal enlarged B cells, consistent with a diagnosis of diffuse large B-cell lymphoma.

CONCLUSION: A diagnosis of lymphoma should be considered when adrenal lesions shrink following even a single low dose of dexamethasone administered as a part of a diagnostic test.

PMID:34095465 | PMC:PMC8053686 | DOI:10.1016/j.aace.2020.11.022

Permalink for 'circRNA-TBC1D4, circRNA-NAALAD2 and circRNA-TGFBR3: Selected Key circRNAs in Neuroblastoma and Their Associations with Clinical Features'

circRNA-TBC1D4, circRNA-NAALAD2 and circRNA-TGFBR3: Selected Key circRNAs in Neuroblastoma and Their Associations with Clinical Features

Fetched: June 8th, 2021, 5:00am GMT by Weihong Lin

Cancer Manag Res. 2021 May 28;13:4271-4281. doi: 10.2147/CMAR.S297316. eCollection 2021.

ABSTRACT

OBJECTIVE: The roles of circRNAs in neuroblastoma (NB) are unclear. We used next-generation sequencing to detect the circRNA expression profiles in NB to identify the key circRNAs and analyzed the relationships between the circRNAs and clinical features.

METHODS: Five paired neuroblastoma tumor and adjacent normal fetal adrenal medulla samples were collected for high-throughput RNA sequencing. Bioinformatics analysis was performed for functional annotation of the host genes of differentially expressed circRNAs. Validation of dysregulated circRNAs was performed by real-time quantitative reverse transcription polymerase chain reaction. The relationships between the key circRNAs and clinical features were analyzed. In addition, overexpression of key circRNAs in an NB cell line, as well as cell proliferation assays, colony formation assays and cell migration assays, was conducted to investigate the biological functions of key circRNAs.

RESULTS: A total of 4704 differentially expressed circRNAs were found, including 2462 up-regulated and 2242 down-regulated circRNAs. According to our previous studies, the predicted target circRNAs of miR-21 involved in tumorigenic signaling pathways were selected, including circRNA-TBC1D4, circRNA-NAALAD2 and circRNA-TGFBR3. These circRNAs were associated with clinical features, and the circRNA expression was significantly lower (P < 0.05) in the NB tissues than in normal adrenal tissues. Overexpression of circRNA-TBC1D4 promotes NB cell migration, but not proliferation and colony-formation in vitro.

CONCLUSION: We suggest that circRNA-TBC1D4, circRNA-NAALAD2 and circRNA-TGFBR3 may be cancer suppressor genes, which act by sponging miR-21 in NB. Further investigations are needed to elucidate the underlying mechanism.

PMID:34093041 | PMC:PMC8168971 | DOI:10.2147/CMAR.S297316

Incidental Adrenal Nodules

Fetched: June 8th, 2021, 5:00am GMT by Daniel I Glazer

Radiol Clin North Am. 2021 Jul;59(4):591-601. doi: 10.1016/j.rcl.2021.03.008.

ABSTRACT

Incidentally detected adrenal nodules are common, and prevalence increases with patient age. Although most are benign, it is important for the radiologist to be able to accurately determine which nodules require further testing and which are safely left alone. The American College of Radiology incidental adrenal White Paper provides a structured algorithm based on expert consensus for management of incidental adrenal nodules. If further diagnostic testing is indicated, adrenal computed tomography is the most appropriate test in patients for nodules less than 4 cm. In addition to imaging, biochemical testing and endocrinology referral is warranted to exclude a functioning mass.

PMID:34053607 | DOI:10.1016/j.rcl.2021.03.008

Adrenal tumors provide insight into the role of cortisol in NK cell activity

Fetched: June 6th, 2021, 5:00am GMT by Andrew E Greenstein

Endocr Relat Cancer. 2021 Jun 1:ERC-21-0048.R2. doi: 10.1530/ERC-21-0048. Online ahead of print.

ABSTRACT

Elevated glucocorticoid (GC) activity may limit tumor immune response and immune checkpoint inhibitor (ICI) efficacy. Adrenocortical carcinoma (ACC) provides a unique test case to assess correlates of GC activity, as approximately half of ACC patients exhibit excess GC production (GC+). ACC multi-omics were analyzed to identify molecular consequences of GC+ and assess the rationale for combining the glucocorticoid receptor (GR) antagonist relacorilant with an ICI. GC status, mRNA expression, and DNA mutation and methylation data from 71 adrenal tumors were accessed via The Cancer Genome Atlas. Expression of 858 genes differed significantly between GC- and GC+ ACC cases. KEGG pathway analysis showed higher gene expression of 3 pathways involved in steroid synthesis and secretion in GC+ cases. Fifteen pathways, most related to NK cells and other immune activity, showed lower expression. Hypomethylation was primarily observed in the steroid synthesis pathways. Tumor-infiltrating CD4+ memory (P=.003), CD8+ memory (P=.001), and NKT-cells (P=.014) were depleted in GC+ cases; tumor-associated neutrophils were enriched (P=.001). Given the pronounced differences between GC+ and GC- ACC, the effects of cortisol on NK cells were assessed in vitro (NK cells from human PBMCs stimulated with IL-2 or IL-12/15). Cortisol suppressed, and relacorilant restored, NK cell activation, proliferation, and direct tumor cell killing. Thus, GR antagonism may increase the abundance and function of NK and other immune cells in the tumor microenvironment, promoting immune response in GC+ ACC and other malignancies with GC+. This hypothesis will be tested in a phase 1 trial of relacorilant + ICI.

PMID:34086600 | DOI:10.1530/ERC-21-0048

Permalink for 'Machine learning-based texture analysis for differentiation of radiologically indeterminate small adrenal tumors on adrenal protocol CT scans'

Machine learning-based texture analysis for differentiation of radiologically indeterminate small adrenal tumors on adrenal protocol CT scans

Fetched: June 6th, 2021, 5:00am GMT by Ahmed W Moawad

Abdom Radiol (NY). 2021 Jun 3. doi: 10.1007/s00261-021-03136-2. Online ahead of print.

ABSTRACT

GOAL: To evaluate the ability of radiomic feature extraction and a machine learning algorithm to differentiate between benign and malignant indeterminate adrenal lesions on contrast-enhanced computed tomography (CT) studies.

BACKGROUND: Adrenal "incidentalomas" are adrenal lesions that are accidentally discovered during workup not related to the adrenal glands; they have an incidence as high as 5%. Small adrenal incidentalomas (< 4 cm) with high attenuation values on pre-contrast CT(> 10 HU) need further evaluation to calculate the absolute percentage of washout (APW). If the APW is < 60%, these lesions are considered non-adenomas and commonly classified as indeterminate adrenal lesions. Further workup for indeterminate lesions includes more complicated and expensive radiological studies or invasive procedures like biopsy or surgical resection.

METHODS: We searched our institutional database for indeterminate adrenal lesions with the following characteristics: < 4 cm, pre-attenuation value > 10 HU, and APW < 60%. Exclusion criteria included pheochromocytoma and no histopathological examination. CT images were converted to Nifti format, and adrenal tumors were segmented using Amira software. Radiomic features from the adrenal mask were extracted using PyRadiomics software after removing redundant features (highly pairwise correlated features and low-variance features) using recursive feature extraction to select the final discriminative set of features. Lastly, the final features were used to build a binary classification model using a random forest algorithm, which was validated and tested using leave-one-out cross-validation, confusion matrix, and receiver operating characteristic curve.

RESULTS: We found 40 indeterminate adrenal lesions (21 benign and 19 malignant). Feature extraction resulted in 3947 features, which reduced down to 62 features after removing redundancies. Recursive feature elimination resulted in the following top 4 discriminative features: gray-level size zone matrix-derived size zone non-uniformity from pre-contrast and delayed phases, gray-level dependency matrix-derived large dependence high gray-level emphasis from venous-phase, and gray-level co-occurrence matrix-derived cluster shade from delayed-phase. A binary classification model with leave-one-out cross-validation showed AUC = 0.85, sensitivity = 84.2%, and specificity = 71.4%.

CONCLUSION: Machine learning and radiomic features extraction can differentiate between benign and malignant indeterminate adrenal tumors and can be used to direct further workup with high sensitivity and specificity.

PMID:34085089 | DOI:10.1007/s00261-021-03136-2

Virilising adrenocortical carcinoma

Fetched: June 6th, 2021, 5:00am GMT by Diogo Nunes Correia

BMJ Case Rep. 2021 Jun 2;14(6):e242895. doi: 10.1136/bcr-2021-242895.

ABSTRACT

Adrenocortical carcinoma (ACC) is a rare malignancy, with an estimated annual incidence of 0.7-2 cases per million and a median overall survival of 3-4 years. Hormone-secreting ACCs represent most cases; of these, only a small minority presents with virilisation alone. Early diagnosis is key to increase the chances of a better outcome. Here, we report a case of a 41-year-old woman who presented with menstrual irregularities, hirsutism and virilising symptoms, associated with abdominal discomfort and constitutional symptoms. On physical examination, there was a palpable mass in the right upper quadrant. Laboratory workup revealed elevated serum androgens. The imaging study showed a 163×110×122 cm right adrenal mass with features consistent with ACC and suggested potential hepatic invasion. Our patient underwent surgical resection, and the histopathological findings confirmed the diagnosis. She was referred to a specialised centre for follow-up and adjuvant therapy.

PMID:34083198 | PMC:PMC8174502 | DOI:10.1136/bcr-2021-242895

Immune checkpoint inhibitor combination therapies very frequently induce secondary adrenal insufficiency

Fetched: June 4th, 2021, 5:00am GMT by Katsunori Manaka

Sci Rep. 2021 Jun 2;11(1):11617. doi: 10.1038/s41598-021-91032-6.

ABSTRACT

Immune checkpoint inhibitors (ICIs) are potent therapeutic options for many types of advanced cancer. The expansion of ICIs use however has led to an increase in immune-related adverse events (irAEs). Secondary adrenal insufficiency (AI) can be life-threatening especially in patients with delayed diagnosis. We retrospectively investigated secondary AI in ICI-treated patients. A total of 373 cancer patients treated with ICIs were included and evaluated. An adrenocorticotropic hormone (ACTH) deficiency was described in 13 patients. Among 24 patients with a combination of nivolumab and ipilimumab therapy, 7 patients (29%) developed secondary AI in a median time of 8 weeks during the combination therapy and 2 of 15 patients (13%) developed isolated ACTH deficiency during maintenance nivolumab monotherapy following the combination therapy. More than half of the patients (4/7) with a combination therapy-induced multiple anterior hormone deficiencies was diagnosed as secondary AI based on regular ACTH and cortisol tests with slight subjective symptoms. Secondary AI can arise frequently and rapidly in cancer patients receiving a combination ICI therapy, and thus we speculate active surveillance of AI using regular ACTH and cortisol tests during the combination therapy might be useful for avoiding life-threatening conditions due to secondary AI.

PMID:34078988 | PMC:PMC8172846 | DOI:10.1038/s41598-021-91032-6

Vitamin D supplementation for the treatment of COVID-19: a living systematic review

Fetched: June 4th, 2021, 5:00am GMT by Julia Kristin Stroehlein

Cochrane Database Syst Rev. 2021 May 24;5:CD015043. doi: 10.1002/14651858.CD015043.

ABSTRACT

BACKGROUND: The role of vitamin D supplementation as a treatment for COVID-19 has been a subject of considerable discussion. A thorough understanding of the current evidence regarding the effectiveness and safety of vitamin D supplementation for COVID-19 based on randomised controlled trials is required.

OBJECTIVES: To assess whether vitamin D supplementation is effective and safe for the treatment of COVID-19 in comparison to an active comparator, placebo, or standard of care alone, and to maintain the currency of the evidence, using a living systematic review approach.

SEARCH METHODS: We searched the Cochrane COVID-19 Study Register, Web of Science and the WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies without language restrictions to 11 March 2021.

SELECTION CRITERIA: We followed standard Cochrane methodology. We included randomised controlled trials (RCTs) evaluating vitamin D supplementation for people with COVID-19, irrespective of disease severity, age, gender or ethnicity. We excluded studies investigating preventive effects, or studies including populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)).

DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. To assess bias in included studies, we used the Cochrane risk of bias tool (ROB 2) for RCTs. We rated the certainty of evidence using the GRADE approach for the following prioritised outcome categories: individuals with moderate or severe COVID-19: all-cause mortality, clinical status, quality of life, adverse events, serious adverse events, and for individuals with asymptomatic or mild disease: all-cause mortality, development of severe clinical COVID-19 symptoms, quality of life, adverse events, serious adverse events.

MAIN RESULTS: We identified three RCTs with 356 participants, of whom 183 received vitamin D. In accordance with the World Health Organization (WHO) clinical progression scale, two studies investigated participants with moderate or severe disease, and one study individuals with mild or asymptomatic disease. The control groups consisted of placebo treatment or standard of care alone. Effectiveness of vitamin D supplementation for people with COVID-19 and moderate to severe disease We included two studies with 313 participants. Due to substantial clinical and methodological diversity of both studies, we were not able to pool data. Vitamin D status was unknown in one study, whereas the other study reported data for vitamin D deficient participants. One study administered multiple doses of oral calcifediol at days 1, 3 and 7, whereas the other study gave a single high dose of oral cholecalciferol at baseline. We assessed one study with low risk of bias for effectiveness outcomes, and the other with some concerns about randomisation and selective reporting. All-cause mortality at hospital discharge (313 participants) We found two studies reporting data for this outcome. One study reported no deaths when treated with vitamin D out of 50 participants, compared to two deaths out of 26 participants in the control group (Risk ratio (RR) 0.11, 95% confidence interval (CI) 0.01 to 2.13). The other study reported nine deaths out of 119 individuals in the vitamin D group, whereas six participants out of 118 died in the placebo group (RR 1.49, 95% CI 0.55 to 4.04]. We are very uncertain whether vitamin D has an effect on all-cause mortality at hospital discharge (very low-certainty evidence). Clinical status assessed by the need for invasive mechanical ventilation (237 participants) We found one study reporting data for this outcome. Nine out of 119 participants needed invasive mechanical ventilation when treated with vitamin D, compared to 17 out of 118 participants in the placebo group (RR 0.52, 95% CI 0.24 to 1.13). Vitamin D supplementation may decrease need for invasive mechanical ventilation, but the evidence is uncertain (low-certainty evidence). Quality of life We did not find data for quality of life. Safety of vitamin D supplementation for people with COVID-19 and moderate to severe disease We did not include data from one study, because assessment of serious adverse events was not described and we are concerned that data might have been inconsistently measured. This study reported vomiting in one out of 119 participants immediately after vitamin D intake (RR 2.98, 95% CI 0.12 to 72.30). We are very uncertain whether vitamin D supplementation is associated with higher risk for adverse events (very low-certainty). Effectiveness and safety of vitamin D supplementation for people with COVID-19 and asymptomatic or mild disease We found one study including 40 individuals, which did not report our prioritised outcomes, but instead data for viral clearance, inflammatory markers, and vitamin D serum levels. The authors reported no events of hypercalcaemia, but recording and assessment of further adverse events remains unclear. Authors administered oral cholecalciferol in daily doses for at least 14 days, and continued with weekly doses if vitamin D blood levels were > 50 ng/mL.

AUTHORS' CONCLUSIONS: There is currently insufficient evidence to determine the benefits and harms of vitamin D supplementation as a treatment of COVID-19. The evidence for the effectiveness of vitamin D supplementation for the treatment of COVID-19 is very uncertain. Moreover, we found only limited safety information, and were concerned about consistency in measurement and recording of these outcomes. There was substantial clinical and methodological heterogeneity of included studies, mainly because of different supplementation strategies, formulations, vitamin D status of participants, and reported outcomes. There is an urgent need for well-designed and adequately powered randomised controlled trials (RCTs) with an appropriate randomisation procedure, comparability of study arms and preferably double-blinding. We identified 21 ongoing and three completed studies without published results, which indicates that these needs will be addressed and that our findings are subject to change in the future. Due to the living approach of this work, we will update the review periodically.

PMID:34029377 | DOI:10.1002/14651858.CD015043

The Immunotherapy Landscape in Adrenocortical Cancer

Fetched: June 3rd, 2021, 5:00am GMT by Guillaume J Pegna

Cancers (Basel). 2021 May 28;13(11):2660. doi: 10.3390/cancers13112660.

ABSTRACT

Adrenocortical carcinoma (ACC) is a rare cancer of the adrenal gland that is frequently associated with excess production of adrenal hormones. Although surgical resection may be curative in early-stage disease, few effective therapeutic options exist in the inoperable advanced or metastatic setting. Immunotherapies, inclusive of a broad array of immune-activating and immune-modulating antineoplastic agents, have demonstrated clinical benefit in a wide range of solid and hematologic malignancies. Due to the broad activity across multiple cancer types, there is significant interest in testing these agents in rare tumors, including ACC. Multiple clinical trials evaluating immunotherapies for the treatment of ACC have been conducted, and many more are ongoing or planned. Immunotherapies that have been evaluated in clinical trials for ACC include the immune checkpoint inhibitors pembrolizumab, nivolumab, and avelumab. Other immunotherapies that have been evaluated include the monoclonal antibodies figitumumab and cixutumumab directed against the ACC-expressed insulin-like growth factor 1 (IGF-1) receptor, the recombinant cytotoxin interleukin-13-pseudomonas exotoxin A, and autologous tumor lysate dendritic cell vaccine. These agents have shown modest clinical activity, although nonzero in the case of the immune checkpoint inhibitors. Clinical trials are ongoing to evaluate whether this clinical activity may be augmented through combinations with other immune-acting agents or targeted therapies.

PMID:34071333 | PMC:PMC8199088 | DOI:10.3390/cancers13112660

A First Case Report of Orbital Extra-Adrenal Paraganglioma in Cat

Fetched: June 3rd, 2021, 5:00am GMT by Leonardo Leonardi

Vet Sci. 2021 May 14;8(5):86. doi: 10.3390/vetsci8050086.

ABSTRACT

Paraganglioma is a rare neuroendocrine neoplasm originating from paraganglia and consisting of neuroendocrine cells of the sympathetic and parasympathetic nervous system. Extra-adrenal paraganglioma occurs with a low incidence in both humans and animals. This report presents the first case of paraganglioma in a cat with orbital primary location. An 18-year-old spayed female European domestic shorthair cat of 3.60 kg body weight was evaluated in a private veterinary clinic in Perugia, Italy, for a pronounced exophthalmos of the right eye. The cat underwent surgery for the enucleation of the right eye and of the mass. The biopsy samples of the removed tissue were fixed in 10% buffered neutral formalin for histological and immunohistochemical evaluations. Therefore, specific markers were used for immunohistochemical investigations, such as anti-neuron specific enolase (NSE), anti-synaptophysin, anti-glial fibrillary acid protein, anti-cytokeratin and anti-chromogranin. The results of these investigations allowed establishing the final diagnosis of ocular extra-adrenal paraganglioma of the cat.

PMID:34068893 | PMC:PMC8156548 | DOI:10.3390/vetsci8050086

The Sexually Dimorphic Adrenal Cortex: Implications for Adrenal Disease

Fetched: June 3rd, 2021, 5:00am GMT by Rodanthi Lyraki

Int J Mol Sci. 2021 May 5;22(9):4889. doi: 10.3390/ijms22094889.

ABSTRACT

Many adrenocortical diseases are more prevalent in women than in men, but the reasons underlying this sex bias are still unknown. Recent studies involving gonadectomy and sex hormone replacement experiments in mice have shed some light onto the molecular basis of sexual dimorphism in the adrenal cortex. Indeed, it has been shown that gonadal hormones influence many aspects of adrenal physiology, ranging from stem cell-dependent tissue turnover to steroidogenesis and X-zone dynamics. This article reviews current knowledge on adrenal cortex sexual dimorphism and the potential mechanisms underlying sex hormone influence of adrenal homeostasis. Both topics are expected to contribute to personalized and novel therapeutic approaches in the future.

PMID:34063067 | PMC:PMC8124132 | DOI:10.3390/ijms22094889

Laparoscopic adrenalectomy for suspected adrenal mass in lung cancer: ganglioneuroma

Fetched: June 2nd, 2021, 5:00am GMT by Ozgur Elvan Gokten

Tumori. 2021 Jun 1:3008916211020080. doi: 10.1177/03008916211020080. Online ahead of print.

ABSTRACT

BACKGROUND: Adrenalectomy is the gold standard for the treatment of primary adrenal ganglioneuroma. Preoperative differential diagnosis of ganglioneuroma is difficult and histopathologic examination is required to confirm the diagnosis.

PATIENT: A 61-year-old woman, who was followed and treated by the medical oncology department because of lung carcinoma pathology squamous cell T4N0Mx, presented to our clinic due to a 15×8-mm nodule with a calculated relative wash-out rate of 40% in the right adrenal gland lateral edge, which was observed on computed tomography examination.

CONCLUSION: Adrenal ganglioneuroma is a rarely seen, hormonally inactive, benign tumor. Final diagnosis can be made with histopathologic examination. Adrenalectomy is the standard treatment preferred for ganglioneuroma. Knowing the clinical appearance and good pathologic specialization are important adjunct matters in diagnosis. Laparoscopic adrenalectomy has become the gold standard in most patients with adrenal tumors.

PMID:34058924 | DOI:10.1177/03008916211020080

Permalink for 'Utilizing Publicly Available Cancer Clinicogenomic Data on CBioPortal to Compare Epidermal Growth Factor Receptor Mutant and Wildtype Non-Small Cell Lung Cancer'

Utilizing Publicly Available Cancer Clinicogenomic Data on CBioPortal to Compare Epidermal Growth Factor Receptor Mutant and Wildtype Non-Small Cell Lung Cancer

Fetched: June 1st, 2021, 5:00am GMT by Chirag Dhar

Cureus. 2021 Apr 25;13(4):e14683. doi: 10.7759/cureus.14683.

ABSTRACT

Publicly available clinicogenomic data on platforms such as the cancer BioPortal (cBioPortal.org) allow for efficient analyses by researchers with little or no experience working with Big Data. cBioPortal.org also allows for appropriate statistical testing and downloadable images for easy dissemination of findings. In this study, the cBioPortal.org platform was tested and its utility demonstrated by comparing cases of non-small cell lung cancer (NSCLC) with and without epidermal growth factor receptor gene (EGFR) mutations. Patients with EGFR mutations were more likely to be female, of Asian ethnicity, never-smokers, and be diagnosed with lung adenocarcinoma. Metastasis to the pleura, pleural fluid, and liver was common in patients with EGFR mutant NSCLC. On the other hand, lymph node, brain, and adrenal gland metastases were more common in patients with other mutations. While the median overall survival was about the same in the two groups, progression-free survival was significantly shorter in the EGFR mutant group. The mutational landscape was significantly different in the two groups with EGFR mutant NSCLCs having a lower mutational burden. Differences in copy number alterations between the two groups were also noted. The descriptive data generated from this study such as age, gender, smoking history, and histological subtype recapitulate findings of other studies on EGFR mutant NSCLCs. Further prospective and/or preclinical studies are needed to confirm differences noted in this study. cBioPortal.com queries may be used to supplement clinical/pre-clinical studies or to generate novel hypotheses.

PMID:34055528 | PMC:PMC8149776 | DOI:10.7759/cureus.14683

HIV and the Pituitary Gland: Clinical and Biochemical Presentations

Fetched: June 1st, 2021, 5:00am GMT by Joyce Youssef

J Lab Physicians. 2021 Mar;13(1):84-90. doi: 10.1055/s-0041-1723055. Epub 2021 May 19.

ABSTRACT

Human immunodeficiency virus (HIV) can have profound impact on the function of the pituitary gland. We have performed an electronic literature search using the following database: PubMed, Medline, Scopus, and Google Scholar. These databases were searched using the keywords HIV, pituitary glands, cancer, pituitary apoplexy, and infertility. HIV can cause hypopituitarism and also can lead to diabetes insipidus. The impact can be slow and insidious, and diagnosis depends on high index of clinical suspicion. The effect on anterior pituitary gland can be associated with growth hormone deficiency, hypothyroidism, adrenal insufficiency, premature menopause, erectile dysfunction, and infertility. HIV can cause pituitary apoplexy, and this should be treated as an endocrine emergency. Importantly, HIV can be associated with pituitary lymphoma and pituitary cancer. Therefore, joined management between HIV physicians, clinical biochemists and endocrinologists may help in establishing pituitary dysfunction.

PMID:34054243 | PMC:PMC8154342 | DOI:10.1055/s-0041-1723055

Central precocious puberty after resection of a virilising adrenocortical oncocytic tumour

Fetched: June 1st, 2021, 5:00am GMT by Lee Rima Madi

BMJ Case Rep. 2021 May 27;14(5):e239562. doi: 10.1136/bcr-2020-239562.

ABSTRACT

Adrenocortical oncocytic tumours are a histological subtype of adrenal neoplasms with a distinctive morphological appearance. Since these tumours are composed of cells of the adrenal cortex, they may act as functional tumours with excess hormone production. They may cause Cushing's syndrome, inappropriate virilisation or precocious puberty. Though rare during childhood, adrenocortical oncocytic tumours should be suspected in a child with peripheral precocious puberty and marked elevation of dehydroepiandrosterone sulfate levels. We describe a 6-year girl who presented with peripheral precocious puberty due to a functional adrenocortical oncocytic tumour. Three months after tumour removal, she developed true central precocious puberty. This report highlights that peripheral precocious puberty may trigger central precocious puberty, particularly after resolution of the underlying cause of the peripheral precocious puberty.

PMID:34045190 | PMC:PMC8162081 | DOI:10.1136/bcr-2020-239562

Permalink for 'A comparative study of transperitoneal transmesenteric approach versus paracolic sulci approach laparoscopic adrenal tumorectomy for treatment of primary hyperaldosteronism on left side'

A comparative study of transperitoneal transmesenteric approach versus paracolic sulci approach laparoscopic adrenal tumorectomy for treatment of primary hyperaldosteronism on left side

Fetched: June 1st, 2021, 5:00am GMT by L Y Zhang

Zhonghua Yi Xue Za Zhi. 2021 Jun 1;101(20):1513-1517. doi: 10.3760/cma.j.cn112137-20210208-00385.

ABSTRACT

Objective: To compare the therapeutic effect of transperitoneal transmesenteric approach versus paracolic sulci approach laparoscopic adrenal tumorectomy for treatment of left-sided primary hyperaldosteronism. Methods: From January 2017 to July 2019, the clinical data of 70 patients with left-sided primary hyperaldosteronism (PHA) who underwent surgery in the First Hospital of Lanzhou University and five other hospitals in Gansu Province were retrospectively analyzed. There are 43 male and 27 female patients. Among them,28 patients were performed transperitoneal transmesenteric approach laparoscopic adrenal tumorectomy and 42 patients were performed transperitoneal paracolic sulci approach laparoscopic adrenal tumorectomy. The general information and perioperative data of the two groups were compared. Results: All 70 cases of surgery were successfully completed. As compared with the paracolic sulci approach group, the operation time was significantly shorter in the transmesenteric approach group[(26.7±8.8)vs (38.9±7.1)min,P<0.001)], and the estimated blood loss was less in the transmesenteric approach group[45(30,50) vs 50(40,60)ml,P=0.042]. There was no statistically significant difference in the postoperative hospitalization days between the two groups[(4.4±1.0)vs(4.5±1.0)d, P=0.669)]. The electrolytes and aldosterone to renin ratio returned to a healthy level in the postoperative one month, and the blood pressure also returned to a healthy level in 53 (75.7%) patients. Conclusion: Transperitoneal transmesenteric approach laparoscopic adrenal tumorectomy is safe and feasible, with a short operation time and relatively less estimated blood loss.

PMID:34044519 | DOI:10.3760/cma.j.cn112137-20210208-00385

Efficacy and Safety of Anlotinib in Patients with Advanced Non-Small Cell Lung Cancer: A Real-World Study

Fetched: May 29th, 2021, 5:00am GMT by Qiuxia Zhong

Cancer Manag Res. 2021 May 20;13:4115-4128. doi: 10.2147/CMAR.S304838. eCollection 2021.

ABSTRACT

BACKGROUND: Anlotinib is a multi-target tyrosine kinase inhibitor (TKI) independently developed by China, which can inhibit tumor angiogenesis and tumor cell proliferation. The ALTER 0303 study has suggested that anlotinib improved overall survival (OS) and progression-free survival (PFS) in the treatment of advanced non-small cell lung cancer (NSCLC). However, in the real world, the efficacy and safety of anlotinib is not clear. Although relevant retrospective studies have confirmed the efficacy and safety of anlotinib, the sample size is small. And the OS was not observed because of the follow-up time was short. Further studies are still essential to evaluate the efficacy and safety of anlotinib in patients with advanced NSCLC in real-world settings. Related studies have preliminarily shown that anlotinib combined with whole-brain radiotherapy (WBRT) can significantly prolong the survival of patients with brain metastases of NSCLC. This study also discusses the best treatment strategies of patients with brain metastases.

METHODS: A retrospective study was conducted on 206 patients with advanced NSCLC who had treated with anlotinib. The primary endpoints were PFS and OS. The secondary endpoints were objective response rate (ORR), disease control rate (DCR) and safety. Kaplan-Meier survival curves were applied to evaluate the efficacy. Univariate analysis was performed by Log rank testing. Cox regression analysis was utilized to evaluate the significance of potential risk factors obtained from the univariate analysis.

RESULTS: The median PFS (mPFS) was 4.0 (95% CI: 3.607-4.393) months, univariate analysis revealed that patients with longer PFS included epidermal growth factor receptor (EGFR) mutation-negative, Eastern Cooperative Oncology Group performance status (ECOG PS) ≤1, no brain metastases, no liver metastases, no adrenal metastases, or ≤2 distant metastases. Cox regression analysis indicated that patients with EGFR-negative and ECOG PS ≤1 had longer PFS. The median OS (mOS) was 8(95% CI: 6.495-9.505) months. EGFR mutation-negative, previous thoracic radiation therapy, no brain metastases, or ≤2 distant metastases were independent positive predictors of OS. The results of Cox regression indicated that the patients without previous thoracic radiation therapy (hazard ratio: 1.855; 95% CI: 1.162-2.960; p=0.010) had shortened OS. The objective response rate was 10.2%, and the disease control rate was 78.2%. The main treatment-related adverse events (AEs) were generally tolerated. All AEs observed during the trial were controlled after dose reduction or symptomatic treatments, and no death was found to be associated with anlotinib.

CONCLUSION: Anlotinib was well tolerated and effective in patients with advanced NSCLC. Patients with EGFR mutation-negative and ECOG PS ≤1 had longer PFS, and patients without previous thoracic radiation therapy (HR: 1.855, 95% CI 1.162-2.960; P = 0.010) had shorter OS. Further investigations are needed because of small sample.

PMID:34045898 | PMC:PMC8149213 | DOI:10.2147/CMAR.S304838

Silent, isolated ACTH deficiency in malignant melanoma patients treated with immune checkpoint inhibitors

Fetched: May 29th, 2021, 5:00am GMT by Ansgar Heck

BMJ Case Rep. 2021 May 27;14(5):e241981. doi: 10.1136/bcr-2021-241981.

ABSTRACT

Treatment with immune checkpoint inhibitors (ICI) has drastically improved the prognosis for melanoma patients, but immune-mediated adverse events can occur in any organ, including the pituitary. In ICI-induced hypophysitis, lymphocytic infiltration and hypersensitivity reactions cause headache and pituitary deficiency. Most cases with ICI-induced hypophysitis develop central adrenal insufficiency. Here, we describe three patients treated with anticytotoxic T-lymphocyte-associated protein 4 (ipilimumab) for metastatic malignant melanoma: case 1 was asymptomatic when hypocortisolism was suspected; case 2 had symptoms of hypocortisolism and suspected severe systemic infection; case 3 had unspecific fatigue. In all cases, routine cortisol measurements and clinical suspicion (cases 2 and 3) led to the diagnosis of adrenocortical hormone (ACTH) deficiency and thereby central adrenal insufficiency. Undiagnosed and untreated, central adrenal insufficiency results in adrenal crisis. In patients treated with ICI, particularly, ipilimumab, hypophysitis and ACTH deficiency must be considered if morning cortisol is low or unspecific clinical symptoms of hypocortisolism are present.

PMID:34045201 | PMC:PMC8162090 | DOI:10.1136/bcr-2021-241981

Permalink for 'Comparison of Posterior Retroperitoneoscopic Adrenalectomy Versus Lateral Transperitoneal Laparoscopic Adrenalectomy for Adrenal Tumors: A Systematic Review and Meta-Analysis'

Comparison of Posterior Retroperitoneoscopic Adrenalectomy Versus Lateral Transperitoneal Laparoscopic Adrenalectomy for Adrenal Tumors: A Systematic Review and Meta-Analysis

Fetched: May 28th, 2021, 5:00am GMT by Chunyang Meng

Front Oncol. 2021 May 10;11:667985. doi: 10.3389/fonc.2021.667985. eCollection 2021.

ABSTRACT

OBJECTIVE: To discuss the differences in the effectiveness and security for adrenal tumors by posterior retroperitoneoscopic adrenalectomy (PRA) and lateral transperitoneal laparoscopic adrenalectomy (LTA).

METHODS: We systematically searched PubMed, Embase, Scopus database and Cochrane Library, and the date was from above database establishment to November 2020. Stata 16 was used for calculation and statistical analyses.

RESULTS: Nine studies involving eight hundred patients were included. The following differences were observed in favor of PRA vs LTA: less operative time (MD: -22.5; 95% CI -32.57 to -12.45; P=0.000), Fewer estimated blood loss (MD: -15.17; 95% CI -26.63 to -3.72; P=0.009), lower intensity of postoperative pain (MD: -0.56; 95% CI, -1.05 to -0.07; P=0.026), shorter length of hospital stay (MD: -1.15; 95% CI -1.94 to -0.36; P=0.04). No differences were shown in conversion rate (OR 2.07; 95%CI 0.71 to 6.03; P=0.181) and complications (OR 0.85;95% CI 0.46 to 1.56; P=0.597).

CONCLUSIONS: Posterior retroperitoneoscopic adrenalectomy was clinically superior to lateral transperitoneal laparoscopic adrenalectomy for adrenal tumors in operative time, estimated blood loss, length of hospital stay, and postoperative pain. Only in term of conversion rate and complications, both were similar.

PMID:34041031 | PMC:PMC8142855 | DOI:10.3389/fonc.2021.667985

Adrenal Disorders in the Tropics

Fetched: May 27th, 2021, 5:00am GMT by Pradip Mukhopadhyay

2021 May 22. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, Dungan K, Grossman A, Hershman JM, Hofland J, Kalra S, Kaltsas G, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, McGee EA, McLachlan R, Morley JE, New M, Purnell J, Sahay R, Singer F, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–.

ABSTRACT

The adrenal gland in conjunction with the pituitary gland is one of the major components of the endocrine system and regulates blood volume, blood pressure, serum electrolytes, and stress responses. Dysfunction of the adrenal glands may be related to diseases of the adrenal glands or pituitary gland. Adrenal disorders may present either due to structural or functional abnormalities. In the tropical countries, adrenal insufficiency is primarily due to adrenal infection by tuberculosis, adrenal mycosis infections, and adrenal hemorrhages. HIV (Human immunodeficiency virus) related adrenal problems are also common. Adrenal dysfunction due to pituitary disorders still occur frequently in tropical region and include Sheehan’s syndrome, vasculotoxic snake bite, and thalassemia. Adrenal hormone excess typically occurs secondary to exogenous glucocorticoid use. Adrenal disorders that occur in the developed world occur with similar frequencies in tropical regions. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:34033308 | Bookshelf:NBK570657

The Management of Type 1 Diabetes

Fetched: May 27th, 2021, 5:00am GMT by Savitha Subramanian

ABSTRACT

Type 1 diabetes (T1D) is an autoimmune disease characterized by progressive pancreatic beta-cell loss resulting in insulin deficiency and hyperglycemia. Exogenous insulin therapy is essential to prevent fatal complications from hyperglycemia. The Diabetes Control and Complications Trial and its long-term follow up, the Epidemiology of Diabetes and its Complications study, demonstrated that stringent glycemic control with intensive insulin therapy can prevent or postpone progression of microvascular disease and reduce risk for macrovascular disease and all-cause mortality. In addition, data obtained from the T1D Exchange, a registry of T1D patients founded in 2010, has become an invaluable resource for scientists worldwide, facilitating collaboration and accelerating understanding of prevailing diabetes practices. Insulin therapy using rapid- and long-acting insulin analogs is the mainstay of management of T1D. Insulin delivery is achieved subcutaneously using multiple daily injections or subcutaneous insulin infusion using insulin pumps. Effective management also involves use of self-monitoring of blood glucose using improved blood glucose meters, continuous glucose monitoring (CGM) devices, and newer insulin pumps with integrated sensor-augmented systems. Addressing psychosocial aspects of T1D plays a crucial role in effective disease management. Strategies to manage T1D are rapidly evolving. In addition to newer insulins, adjunctive non-insulin therapies such as use of incretin agents and SGLT-2 and combination SGLT-1/2 inhibitors are being actively pursued. CGM technology combined with glucose prediction algorithms has allowed for the development of artificial pancreas delivery systems. Cellular replacement options include pancreas and islet cell transplantation which can restore euglycemia but are limited by donor availability and the need for chronic immunosuppression. Newer strategies under development include islet cell encapsulation techniques, which might obviate the need for immunosuppression. Smart-insulin delivery systems, capable of releasing insulin depending on ambient glucose, are also being evaluated. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:25905338 | Bookshelf:NBK279114

Neuroendocrine Control of Body Energy Homeostasis

Fetched: May 27th, 2021, 5:00am GMT by Alison H. Affinati

2021 May 15. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, Dungan K, Grossman A, Hershman JM, Hofland J, Kalra S, Kaltsas G, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, McGee EA, McLachlan R, Morley JE, New M, Purnell J, Sahay R, Singer F, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–.

ABSTRACT

The brain integrates the response to a variety of signals of energy need and availability to match food intake with energy expenditure, thereby maintaining body weight stability. Early work with rodent models with disrupted energy balance (generally obesity) identified many hypothalamic genes and signaling pathways that impact energy homeostasis. More recent studies have identified hindbrain circuits that interact with peripheral metabolic signals and hypothalamic circuits to impact energy balance. Feeding, signals of energy utilization, and hormonal signals of energy stores (such as leptin) modulate gene expression and neurotransmission in specialized circuits within the hypothalamus and brainstem to control food intake. While many of these circuits also control energy expenditure, the effects on body weight that arise from alterations in energy expenditure are generally more modest than the effects of produced by changes in feeding. Although most of the mechanistic work that defined the systems that control energy balance utilized rodent models, these systems have human orthologs whose disruption produces phenotypes comparable to those observed in rodents, confirming their conserved function. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:34033309 | Bookshelf:NBK570658

Exercise Treatment of Obesity

Fetched: May 27th, 2021, 5:00am GMT by Tori Stone

ABSTRACT

Surveillance data from the general US population indicate a continued increase in the prevalence of overweight and obesity that is consistent with weight gain trends observed globally among industrialized countries. Physical inactivity and obesity are closely linked conditions and they account for a large burden of chronic disease and impaired function. The underlying agent in the etiology of obesity is a long-term positive energy balance; however, the pathways determining the rate and extent of weight gain due to a positive energy are complex. Engaging in regular, moderate-intensity physical activity for at least 150 min/week can help maintain energy balance and prevent excessive weight gain; however, this minimum requirement may not be sufficient for reversing already-existing obesity and chronic disease. In fact, physical activity closer to 300 min/week may be necessary for successful weight loss and weight loss maintenance. Regimented exercise programs alone may not be the most effective treatment for people with obesity, however. Rather, lifestyle changes that increase total daily energy expenditure need to be accompanied by dietary counseling for reducing daily caloric intake. Also, accumulating the necessary exercise and lifestyle physical activity in intermittent bouts, rather than one long continuous bout, can improve adherence and the success of weight loss regimens. It is also important for both clinicians and patients to understand that a simple solution to obesity treatment does not exist due to the constellation of underlying mechanisms that drive energy balance. Indeed, physiological, behavioral, environmental, and genetic factors play both independent and interrelated roles that contribute to the complex etiology of obesity. Research from numerous scientific disciplines has shaped our understanding of obesity. While the relative contributions of insufficient energy expenditure versus excessive energy intake to obesity development continue to be debated, there is general agreement that exercise is a key element for both prevention and treatment. Future research should focus on the prevention of excess weight gain over the life course. In addition to the behavioral and intervention studies of the past several decades, an understanding of the regulatory processes governing energy intake, energy storage, and energy expenditure and how the reinstatement of exercise can correct the disruption of neural pathways is vital to the future of obesity research. Finally, public health science needs to link with public health practice to better enable the translation of this knowledge into policies that can alter the environment in a way that promotes an active lifestyle for all. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:25905196 | Bookshelf:NBK278961

Hyperglycemic Crises: Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar State

Fetched: May 27th, 2021, 5:00am GMT by Aidar R Gosmanov

2021 May 9. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, Dungan K, Grossman A, Hershman JM, Hofland J, Kalra S, Kaltsas G, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, McGee EA, McLachlan R, Morley JE, New M, Purnell J, Sahay R, Singer F, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–.

ABSTRACT

Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are acute metabolic complications of diabetes mellitus that can occur in patients with both type 1 and 2 diabetes mellitus. Timely diagnosis, comprehensive clinical and biochemical evaluation, and effective management is key to the successful resolution of DKA and HHS. Critical components of the hyperglycemic crises’ management include coordinating fluid resuscitation, insulin therapy, and electrolyte replacement along with the continuous patient monitoring using available laboratory tools to predict the resolution of the hyperglycemic crisis. Understanding and prompt awareness of potential special situations such as DKA or HHS presentation in the comatose state, possibility of mixed acid-base disorders obscuring the diagnosis of DKA, and risk of brain edema during therapy are important to reduce the risks of complications without affecting recovery from hyperglycemic crisis. Identification of factors that precipitated DKA or HHS during the index hospitalization should help prevent subsequent episode of hyperglycemic crisis. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:25905280 | Bookshelf:NBK279052

Ectopic Cushing syndrome in Colombia

Fetched: May 26th, 2021, 5:00am GMT by Vanessa Lopez-Montoya

Arch Endocrinol Metab. 2021 May 18;64(6):687-694. doi: 10.20945/2359-3997000000271.

ABSTRACT

OBJECTIVE: The aim was to describe the clinical features of patients with ectopic Cushing syndrome (ECS) from Colombia and compare these findings with other series to provide the best management for these patients.

METHODS: Records of patients with ECS from 1986 to 2017 were retrospectively reviewed; patients with a diagnosis of adrenal or pituitary Cushing syndrome (CS) were excluded.

RESULTS: Fourteen patients with ECS were analyzed in this study. The mean age was 54.4 (SD 17.1) years, and the female to male ratio was 1.33:1. Regarding the etiology of ECS, four patients had lung carcinoids (28.6%), three had small-cell lung carcinoma (21.4%), three had pancreatic neuroendocrine tumors (21.4%), one had medullary thyroid cancer (7.1%), one had non-metastatic pheochromocytoma (7.1%), one had metastatic thymoma (7.1%) and one patient had an occult source of ACTH (7.1%). The most common clinical features at presentation were moon-face, muscle weakness, diabetes mellitus and hypertension. Hyperpigmentation was present in 36% of patients, and 12 patients had hypokalemia with a mean value of 2.3 mEq/L (SD 0.71). The median basal cortisol, 24-hour urinary free cortisol (UFC) and ACTH were 30.5 ug/dL (IQR 21-59 ug/dL), 2,600 ug/24 h (IQR 253-6,487 ug/24 h) and 91 pg/mL (IQR 31.9-141.9), respectively. Thirteen patients (92.8%) had the site of the primary lesion identified. Six patients had undergone a surgical intervention to address the primary tumor. Resection was curative in 28.5% of patients. Death occurred in 57.1% of patients, and the median overall survival was 27 months. Intrathoracic tumors had the most aggressive behavior.

CONCLUSION: ECS is a rare disease; however, it is associated with high morbidity and mortality. A rapid intervention supported by an interdisciplinary group is required to improve overall survival and quality of life.

PMID:34033277 | DOI:10.20945/2359-3997000000271

Permalink for 'Differences in Clinical Manifestations and Tumor Features Between Metastatic Pheochromocytoma/Paraganglioma Patients With and Without Germline SDHB Mutation'

Differences in Clinical Manifestations and Tumor Features Between Metastatic Pheochromocytoma/Paraganglioma Patients With and Without Germline SDHB Mutation

Fetched: May 26th, 2021, 5:00am GMT by Yunying Cui

Endocr Pract. 2021 Apr;27(4):348-353. doi: 10.1016/j.eprac.2020.09.015. Epub 2020 Dec 14.

ABSTRACT

OBJECTIVE: To compare metastatic pheochromocytoma/paraganglioma (MPP) patients with germline SDHB mutations (SDHB MPP) and without SDHB mutations (non-SDHB MPP) in terms of baseline clinical manifestations, tumor characteristics, and outcomes.

METHODS: Clinical data were retrospectively reviewed in 101 MPP patients, including 34 SDHB MPP patients and 61 non-SDHB MPP patients.

RESULTS: SDHB MPP patients presented at a younger age at onset, diagnosis, or metastasis (25 ± 16 vs 36 ± 14, 28 ± 17 vs 38 ± 15, and 31 ± 17 vs 44 ± 14 years old, respectively, P < .01 for all) than non-SDHB patients. Compared with their non-SDHB counterparts, SDHB patients were more likely to have paragangliomas (83% vs 47%, P < .05), synchronous metastases (44% vs 23%, P < .05), bone metastases (80% vs 48%, P < .01), and a shorter progression-free survival (3 years vs 5 years, P < .01). The Ki-67 index was higher in SDHB tumors (P < .05). The 5- and 10-year survival rates were 79% and 74%, respectively, in all patients. Seventeen patients died from MPP, and the time from metastasis to death in patients who had received systemic therapy was significantly longer than in those who had not (3.1 ± 1.5 vs 1.4 ± 0.7 years, P < .01).

CONCLUSION: Compared with MPP patients without SDHB mutations, MPP patients with SDHB mutations were younger at onset, diagnosis, or metastasis; had a higher incidence of synchronous metastases, higher ratio of paraganglioma, and higher Ki-67 index; had a shorter postoperative progression-free survival; and were more likely to develop bone metastasis or sole liver metastasis. Our results suggest that patients with SDHB mutations should be identified early and monitored regularly to achieve optimal clinical outcomes.

PMID:34024343 | DOI:10.1016/j.eprac.2020.09.015

Permalink for 'Hereditary pheochromocytoma/paraganglioma syndrome with a novel mutation in the succinate dehydrogenase subunit B gene in a Japanese family: two case reports'

Hereditary pheochromocytoma/paraganglioma syndrome with a novel mutation in the succinate dehydrogenase subunit B gene in a Japanese family: two case reports

Fetched: May 26th, 2021, 5:00am GMT by Rei Hirose

J Med Case Rep. 2021 May 22;15(1):282. doi: 10.1186/s13256-021-02852-z.

ABSTRACT

BACKGROUND: Pheochromocytoma and paraganglioma caused by succinate dehydrogenase gene mutations is called hereditary pheochromocytoma/paraganglioma syndrome. In particular, succinate dehydrogenase subunit B mutations are important because they are strongly associated with the malignant behavior of pheochromocytoma and paraganglioma . This is a case report of a family of hereditary pheochromocytoma/paraganglioma syndrome carrying a novel mutation in succinate dehydrogenase subunit B.

CASE PRESENTATION: A 19-year-old Japanese woman, whose father died of metastatic paraganglioma, was diagnosed with abdominal paraganglioma, and underwent total resection. Succinate dehydrogenase subunit B genetic testing detected a splice-site mutation, c.424-2delA, in her germline and paraganglioma tissue. Afterwards, the same succinate dehydrogenase subunit B mutation was detected in her father's paraganglioma tissues. In silico analysis predicted the mutation as "disease causing." She is under close follow-up, and no recurrence or metastasis has been observed for 4 years since surgery.

CONCLUSIONS: We detected a novel succinate dehydrogenase subunit B mutation, c.424-2delA, in a Japanese family afflicted with hereditary pheochromocytoma/paraganglioma syndrome and found the mutation to be responsible for hereditary pheochromocytoma/paraganglioma syndrome. This case emphasizes the importance of performing genetic testing for patients with pheochromocytoma and paraganglioma suspected of harboring the succinate dehydrogenase subunit B mutation (that is, metastatic, extra-adrenal, multiple, early onset, and family history of pheochromocytoma and paraganglioma) and offer surveillance screening to mutation carriers.

PMID:34020699 | PMC:PMC8140422 | DOI:10.1186/s13256-021-02852-z

Angiosarcoma of the Adrenal Gland

Fetched: May 26th, 2021, 5:00am GMT by Lori A Erickson

Mayo Clin Proc. 2021 May;96(5):1376-1378. doi: 10.1016/j.mayocp.2021.03.032.

NO ABSTRACT

PMID:33958072 | DOI:10.1016/j.mayocp.2021.03.032

Tumour brain: pre-treatment cognitive and affective disorders caused by peripheral cancers

Fetched: May 25th, 2021, 5:00am GMT by Myrthe Mampay

Br J Pharmacol. 2021 May 24. doi: 10.1111/bph.15571. Online ahead of print.

ABSTRACT

People that develop extra-cranial cancers often display comorbid neurological disorders, such as anxiety, depression, and cognitive impairment, even before commencement of chemotherapy. This suggests bidirectional crosstalk between non-central nervous system tumours and the brain, which can regulate peripheral tumour growth. However, the reciprocal neurological effects of tumour progression on brain homeostasis are not well understood. Here, we review brain regions involved in regulating peripheral tumour development and how they, in turn, are adversely impacted by advancing tumour burden. Tumour-induced activation of the immune system, blood-brain-barrier breakdown, and chronic neuroinflammation can lead to circadian rhythm dysfunction, sleep disturbances, aberrant glucocorticoid production, decreased hippocampal neurogenesis and dysregulation of neural network activity, resulting in depression and memory impairments. Given that cancer-related cognitive impairment diminishes patient quality of life, reduces adherence to chemotherapy, and worsens cancer prognosis, it is essential that more research is focused at understanding how peripheral tumours impact brain homeostasis.

PMID:34029379 | DOI:10.1111/bph.15571

Primary Angiosarcoma of the Adrenal Gland: Report of 2 Cases and Review of the Literature

Fetched: May 25th, 2021, 5:00am GMT by Alexander Ladenheim

Int J Surg Pathol. 2021 May 24:10668969211020099. doi: 10.1177/10668969211020099. Online ahead of print.

ABSTRACT

Primary adrenal angiosarcoma is a rare, malignant, vascular neoplasm. These neoplasms typically arise in middle age (median age of 60 years) and are more common in males (65%) than in females. Although rare, these neoplasms are aggressive with a propensity for local recurrence and metastasis and a median survival of 18 months. We present 2 cases of primary adrenal angiosarcoma with synchronous, ipsilateral adrenocortical adenomas. We review the cases of adrenal angiosarcoma reported since 1988 and discuss their clinical and histopathologic characteristics.

PMID:34029146 | DOI:10.1177/10668969211020099

Dissociated response related to corticosteroids in lung cancer treated by immunotherapy: A case report

Fetched: May 25th, 2021, 5:00am GMT by Quentin Dominique Thomas

Clin Case Rep. 2021 Mar 24;9(5):e03973. doi: 10.1002/ccr3.3973. eCollection 2021 May.

ABSTRACT

We report the case of a patient with a complete metastatic adrenal response on Pembrolizumab for metastatic lung cancer. Treatment with a systemic corticosteroid-induced a time-dependent progression at his metastatic site. Surprisingly, after stopping the corticosteroid, we observed a new complete response in long-term adrenal metastases.

PMID:34026127 | PMC:PMC8117819 | DOI:10.1002/ccr3.3973

Permalink for 'Pemetrexed-Platinum With or Without Bevacizumab for Chinese Chemo-Naive Advanced Lung Adenocarcinoma Patients: A Real-World Study'

Pemetrexed-Platinum With or Without Bevacizumab for Chinese Chemo-Naive Advanced Lung Adenocarcinoma Patients: A Real-World Study

Fetched: May 25th, 2021, 5:00am GMT by Xin Li

Front Pharmacol. 2021 May 7;12:649222. doi: 10.3389/fphar.2021.649222. eCollection 2021.

ABSTRACT

Despite recent advances in the treatment of advanced non-small-cell lung cancer (NSCLC), bevacizumab plus platinum-based doublet chemotherapy remains a commonly used first-line regimen. This study was conducted to compare the efficacy and safety of pemetrexed-platinum with or without bevacizumab in Chinese chemo-naive advanced lung adenocarcinoma patients in a real-world setting. We retrospectively collected 100 patients who received pemetrexed-platinum with or without bevacizumab (PP, n = 46; Bev+PP, n = 54) until disease progression or unacceptable toxicity. Clinical characteristics of patients were balanced, except for the proportion of stage IV b+c (Bev+PP and PP: 67.4 vs. 37.0%, p = 0.0066). Bev+PP significantly improved the objective response rate (ORR, 65 vs. 30%, p = 0.0004) and progression-free survival (PFS, 7.4 vs. 6.8 months, p = 0.009), but not overall survival (OS, 17.5 vs. 15.0 months, p = 0.553) compared with PP. Treatment (p = 0.001), gender (p = 0.008), adrenal metastasis (p = 0.001), and liver metastasis (p = 0.013) were independent risk factors for PFS. Patients with adrenal metastasis tended to be at the highest risk of not benefiting from bevacizumab addition (HR [95% CI]: 2.244 [0.6495-7.753]). The safety profile was acceptable, and grade ≥3 toxicity occurred similarly. This study showed that pemetrexed-platinum plus bevacizumab was effective compared to chemotherapy alone in Chinese patients with advanced NSCLC.

PMID:34025415 | PMC:PMC8138310 | DOI:10.3389/fphar.2021.649222

Permalink for 'Single-Center Prospective Cohort Study on the Histopathology, Genotype, and Postsurgical Outcomes of Patients With Primary Aldosteronism'

Single-Center Prospective Cohort Study on the Histopathology, Genotype, and Postsurgical Outcomes of Patients With Primary Aldosteronism

Fetched: May 25th, 2021, 5:00am GMT by Lucie S Meyer

Hypertension. 2021 May 24:HYPERTENSIONAHA12117348. doi: 10.1161/HYPERTENSIONAHA.121.17348. Online ahead of print.

ABSTRACT

Unilateral forms of primary aldosteronism are usually surgically treated to remove the source of aldosterone excess. After adrenalectomy, aldosteronism persists in some patients indicating abnormal aldosterone production from the unresected gland. Our objective was to investigate histopathology, genotype, and postsurgical outcomes in a 3-year prospective cohort of surgically treated patients for primary aldosteronism (from 2016 to 2018). The cohort comprised 60 consecutively operated patients categorized with classical or nonclassical histopathologic findings of unilateral primary aldosteronism. In the classical group were 45 solitary aldosterone-producing adenomas or dominant aldosterone-producing nodules; in the nonclassical group were 15 cases of multiple aldosterone-producing micronodules or nodules (12 cases) or aldosterone-producing diffuse hyperplasia (3 cases). The classical group displayed higher baseline plasma aldosterone concentrations (262 versus 155 pg/mL, P=0.008) and an increased aldosterone-to-renin ratio (81 versus 42, P=0.002). A high proportion of the classical group achieved complete biochemical success (97.6% versus 66.7% in the nonclassical group, P=0.002). The nonclassical versus classical group displayed an increased ratio of absolute aldosterone concentration in the contralateral adrenal vein to peripheral vein at adrenal venous sampling (3.8 versus 2.0, P=0.004). Variants in aldosterone-driver genes were identified in 85% of 41 aldosterone-producing adenomas and were excluded in the remaining 15% by CYP11B2 guided next-generation sequencing. There were no differences in clinical or biochemical outcomes in patients with a solitary aldosterone-producing adenoma categorized by KCNJ5 mutation status. In conclusion, adrenals with a nonclassical histopathology of unilateral primary aldosteronism are associated with a higher incidence of postsurgical disease persistence and increased aldosterone production from the unresected adrenal.

PMID:34024122 | DOI:10.1161/HYPERTENSIONAHA.121.17348

Chromaffin Cell Cancer

Fetched: May 25th, 2021, 5:00am GMT by Ateeq Mubarik

2021 May 19. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan–.

ABSTRACT

The term pheochromocytoma first described by Mr. Pick in 1912. Pheochromocytoma is a tumor that arises from chromaffin cells present in the adrenal medulla or paraganglion cells. It named in this way as these tissues have a special reaction on the application of a chromium salt. Dr. Charles Mayo presented the first case of pheochromocytoma in 1937 with a clinical diagnosis and therapeutic surgical resection.

PMID:30570981 | Bookshelf:NBK535360

Li-Fraumeni Syndrome

Fetched: May 25th, 2021, 5:00am GMT by Surya K. Aedma

2021 May 15. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan–.

ABSTRACT

In 1969, a remarkable cancer predisposition syndrome was reported by Li and Fraumeni. Li-Fraumeni syndrome (LFS) is an inherited autosomal dominant disorder that is usually associated with abnormalities in the tumor suppressor protein P53 gene (TP53) located on chromosome 17p13. It is also known as the sarcoma, breast, leukemia, and adrenal gland (SBLA) cancer syndrome. LFS variants include LFS1, LFS2, LFSL. LFS1 is associated with mutations in TP53, a tumor suppressor gene. LFS2 is associated with mutations in CHEK2 (checkpoint kinase two), also a tumor suppressor gene. LFS-L are individuals that do not have detectable mutations in P53.

PMID:30335319 | Bookshelf:NBK532286

Permalink for 'GWAS of allometric body-shape indices in UK Biobank identifies loci suggesting associations with morphogenesis, organogenesis, adrenal cell renewal and cancer'

GWAS of allometric body-shape indices in UK Biobank identifies loci suggesting associations with morphogenesis, organogenesis, adrenal cell renewal and cancer

Fetched: May 23rd, 2021, 5:00am GMT by Sofia Christakoudi

Sci Rep. 2021 May 21;11(1):10688. doi: 10.1038/s41598-021-89176-6.

ABSTRACT

Genetic studies have examined body-shape measures adjusted for body mass index (BMI), while allometric indices are additionally adjusted for height. We performed the first genome-wide association study of A Body Shape Index (ABSI), Hip Index (HI) and the new Waist-to-Hip Index and compared these with traditional indices, using data from the UK Biobank Resource for 219,872 women and 186,825 men with white British ancestry and Bayesian linear mixed-models (BOLT-LMM). One to two thirds of the loci identified for allometric body-shape indices were novel. Most prominent was rs72959041 variant in RSPO3 gene, expressed in visceral adipose tissue and regulating adrenal cell renewal. Highly ranked were genes related to morphogenesis and organogenesis, previously additionally linked to cancer development and progression. Genetic associations were fewer in men compared to women. Prominent region-specific associations showed variants in loci VEGFA and HMGA1 for ABSI and KLF14 for HI in women, and C5orf67 and HOXC4/5 for ABSI and RSPO3, VEGFA and SLC30A10 for HI in men. Although more variants were associated with waist and hip circumference adjusted for BMI compared to ABSI and HI, associations with height had previously been reported for many of the additional variants, illustrating the importance of adjusting correctly for height.

PMID:34021172 | PMC:PMC8139988 | DOI:10.1038/s41598-021-89176-6

Permalink for 'Anaplastic lymphoma kinase (alk), a neuroblastoma associated gene, is expressed in neural crest domains during embryonic development of Xenopus'

Anaplastic lymphoma kinase (alk), a neuroblastoma associated gene, is expressed in neural crest domains during embryonic development of Xenopus

Fetched: May 23rd, 2021, 5:00am GMT by Marcela M Moreno

Gene Expr Patterns. 2021 Jun;40:119183. doi: 10.1016/j.gep.2021.119183. Epub 2021 May 19.

ABSTRACT

Neuroblastoma is a neural crest-derived paediatric cancer that is the most common and deadly solid extracranial tumour of childhood. It arises when neural crest cells fail to follow their differentiation program to give rise to cells of the sympathoadrenal lineage. These undifferentiated cells can proliferate and migrate, forming tumours mostly found associated with the adrenal glands. Activating mutations in the kinase domain of anaplastic lymphoma kinase (ALK) are linked to high-risk cases, where extensive therapy is ineffective. However, the role of ALK in embryonic development, downstream signal transduction and in metastatic transformation of the neural crest is poorly understood. Here, we demonstrate high conservation of the ALK protein sequences among vertebrates. We then examine alk mRNA expression in the frog models Xenopus laevis and Xenopus tropicalis. Using in situ hybridisation of Xenopus embryos, we show that alk is expressed in neural crest domains throughout development, suggesting a possible role in neuroblastoma initiation. Lastly, RT-qPCR analyses show high levels of alk expression at tadpole stages. Collectively, these data may begin to elucidate how alk functions in neural crest cells and how its deregulation can result in tumorigenesis.

PMID:34020009 | DOI:10.1016/j.gep.2021.119183

Steroid ligands, the forgotten triggers of nuclear receptor action; implications for acquired resistance to endocrine therapy

Fetched: May 22nd, 2021, 5:00am GMT by Rachel Bleach

Clin Cancer Res. 2021 May 20. doi: 10.1158/1078-0432.CCR-20-4135. Online ahead of print.

ABSTRACT

PURPOSE: There is strong epidemiologic evidence indicating that estrogens may not be the sole steroid drivers of breast cancer. We hypothesize that abundant adrenal androgenic steroid precursors, acting via the androgen receptor (AR), promote an endocrine-resistant breast cancer phenotype.

EXPERIMENTAL DESIGN: AR was evaluated in a primary breast cancer tissue microarray (n = 844). Androstenedione (4AD) levels were evaluated in serum samples (n = 42) from hormone receptor-positive, postmenopausal breast cancer. Levels of androgens, progesterone, and estradiol were quantified using LC/MS-MS in serum from age- and grade-matched recurrent and nonrecurrent patients (n = 6) before and after aromatase inhibitor (AI) therapy (>12 months). AR and estrogen receptor (ER) signaling pathway activities were analyzed in two independent AI-treated cohorts.

RESULTS: AR protein expression was associated with favorable progression-free survival in the total population (Wilcoxon, P < 0.001). Pretherapy serum samples from breast cancer patients showed decreasing levels of 4AD with age only in the nonrecurrent group (P < 0.05). LC/MS-MS analysis of an AI-sensitive and AI-resistant cohort demonstrated the ability to detect altered levels of steroids in serum of patients before and after AI therapy. Transcriptional analysis showed an increased ratio of AR:ER signaling pathway activities in patients failing AI therapy (t test P < 0.05); furthermore, 4AD mediated gene changes associated with acquired AI resistance.

CONCLUSIONS: This study highlights the importance of examining the therapeutic consequences of the steroid microenvironment and demonstrable receptor activation using indicative gene expression signatures.

PMID:34016642 | DOI:10.1158/1078-0432.CCR-20-4135

Continuous and progressive 'wash-in' without 'wash-out' of contrast in adrenal mass: a useful feature of ganglioneuroma

Fetched: May 22nd, 2021, 5:00am GMT by Neeti Agrawal

BMJ Case Rep. 2021 May 19;14(5):e241661. doi: 10.1136/bcr-2021-241661.

ABSTRACT

Computed tomography (CT) scan is a useful and widely performed diagnostic modality to evaluate adrenal masses. Nature of the mass determines the degree of attenuation both in unenhanced and in different phases of contrast enhancement. Benign neurogenic tumours like ganglioneuroma mimicks pheochromocytoma and adrenocortical carcinoma in non-contrast CT scan. The 'adrenal protocol' routinely calculates the wash-out pattern at delayed venous phase (DVP) (15 min) following contrast administration to differentiate majority of benign masses from the malignant ones. Ganglioneuromas typically exhibit continuous wash-in of contrast where enhancement gradually increases to attain its peak in DVP. Such wash-in pattern is different from the wash-out pattern observed in pheochromocytomas or adrenocortical adenomas or carcinomas. Presence of this wash-in pattern provides a useful clue to the clinician for underlying ganglioneuroma in hormonally inactive adrenal masses with suspicious morphological appearances. This wash-in pattern also effectively rules out any malignant potential of ganglioneuroma, and thus helps in preoperative decision-making.

PMID:34011673 | PMC:PMC8137236 | DOI:10.1136/bcr-2021-241661

Carcinoma of unknown primary origin with isolated adrenal metastasis: a report of two cases

Fetched: May 21st, 2021, 5:00am GMT by Mitsuhiro Kometani

Endocr J. 2021 May 18. doi: 10.1507/endocrj.EJ21-0141. Online ahead of print.

ABSTRACT

The adrenal glands are one of the most common sites of malignant tumor metastasis. However, metastatic adrenal carcinoma of unknown primary origin with localized adrenal gland involvement is an extremely rare condition. Herein, we reported two cases of carcinoma of unknown primary origin with isolated adrenal metastasis. In the first case, back pain was the trigger; while in the second case, the triggers were low fever and weight loss. Metabolic abnormalities such as hypertension and obesity were not detected in either case. Neither patient had relevant previous medical histories, including malignancy. However, both had a long-term history of smoking. Systemic imaging studies revealed only adrenal tumors and surrounding lesions. Primary adrenocortical carcinoma was initially suspected, and chemotherapy including mitotane was considered. However, due to difficulty in complete resection of the tumor, core needle tumor biopsies were performed. Histopathological examination of biopsy specimens led to the diagnosis of carcinoma of unknown primary origin with isolated adrenal metastasis. In both cases, additional laboratory testing showed high levels of serum squamous cell carcinoma-related antigen and serum cytokeratin fragment. Malignant lesions confined to the adrenal glands are rare. As in our cases, it could be occasionally difficult to differentiate non-functioning primary adrenocortical carcinoma from metastatic adrenal carcinoma of unknown primary origin localized to the adrenal gland. If the lesion is unresectable and there are elevated levels of several tumor markers with no apparent hormonal excess, core needle tumor biopsy should be considered to differentiate the primary tumor from the metastatic tumor.

PMID:34011784 | DOI:10.1507/endocrj.EJ21-0141

Use of repurposed and adjuvant drugs in hospital patients with covid-19: multinational network cohort study

Fetched: May 21st, 2021, 5:00am GMT by Albert Prats-Uribe

BMJ. 2021 May 11;373:n1038. doi: 10.1136/bmj.n1038.

ABSTRACT

OBJECTIVE: To investigate the use of repurposed and adjuvant drugs in patients admitted to hospital with covid-19 across three continents.

DESIGN: Multinational network cohort study.

SETTING: Hospital electronic health records from the United States, Spain, and China, and nationwide claims data from South Korea.

PARTICIPANTS: 303 264 patients admitted to hospital with covid-19 from January 2020 to December 2020.

MAIN OUTCOME MEASURES: Prescriptions or dispensations of any drug on or 30 days after the date of hospital admission for covid-19.

RESULTS: Of the 303 264 patients included, 290 131 were from the US, 7599 from South Korea, 5230 from Spain, and 304 from China. 3455 drugs were identified. Common repurposed drugs were hydroxychloroquine (used in from <5 (<2%) patients in China to 2165 (85.1%) in Spain), azithromycin (from 15 (4.9%) in China to 1473 (57.9%) in Spain), combined lopinavir and ritonavir (from 156 (<2%) in the VA-OMOP US to 2,652 (34.9%) in South Korea and 1285 (50.5%) in Spain), and umifenovir (0% in the US, South Korea, and Spain and 238 (78.3%) in China). Use of adjunctive drugs varied greatly, with the five most used treatments being enoxaparin, fluoroquinolones, ceftriaxone, vitamin D, and corticosteroids. Hydroxychloroquine use increased rapidly from March to April 2020 but declined steeply in May to June and remained low for the rest of the year. The use of dexamethasone and corticosteroids increased steadily during 2020.

CONCLUSIONS: Multiple drugs were used in the first few months of the covid-19 pandemic, with substantial geographical and temporal variation. Hydroxychloroquine, azithromycin, lopinavir-ritonavir, and umifenovir (in China only) were the most prescribed repurposed drugs. Antithrombotics, antibiotics, H2 receptor antagonists, and corticosteroids were often used as adjunctive treatments. Research is needed on the comparative risk and benefit of these treatments in the management of covid-19.

PMID:33975825 | PMC:PMC8111167 | DOI:10.1136/bmj.n1038

Pheochromocytoma and Paraganglioma in Pregnancy: a New Era

Fetched: May 21st, 2021, 5:00am GMT by Lucinda M Gruber

Curr Cardiol Rep. 2021 May 7;23(6):60. doi: 10.1007/s11886-021-01485-4.

ABSTRACT

PURPOSE OF REVIEW: Pheochromocytoma and paraganglioma (PPGL) in pregnancy is a rare entity and management of these patients is fraught with uncertainty. Our objective is to review current literature and discuss diagnosis and management of these patients.

RECENT FINDINGS: Outcomes of PPGL in pregnancy have improved in recent years. The greatest risk for adverse maternal and fetal outcomes is the diagnosis of PPGL after delivery. Alpha- and beta-adrenergic blockade is well tolerated and is associated with less adverse outcomes. Antepartum surgery is not associated with improved maternal or fetal outcomes. Biochemical testing and cross-sectional imaging should be performed prior to conception for patients with a known germline variant associated with PPGL.

CONCLUSIONS: Medical therapy should be initiated when PPGL is diagnosed in pregnancy. Antepartum surgery should be reserved for special circumstances. Case detection testing in high-risk patients can identify PPGL before pregnancy.

PMID:33961120 | DOI:10.1007/s11886-021-01485-4

The epidemiology and biology of pulmonary metastases

Fetched: May 21st, 2021, 5:00am GMT by William D Gerull

J Thorac Dis. 2021 Apr;13(4):2585-2589. doi: 10.21037/jtd.2020.04.28.

ABSTRACT

Our goal in this chapter is to explore the complex processes of metastasis and why there is a predisposition for this to occur in the lung. In addition, we aim to describe the incidence of pulmonary metastases in various contexts and based on the origin of the primary tumor. There are unique characteristics of the pulmonary system that make metastases more likely to occur in the lung than anywhere else in the body. Some of these characteristics include receiving the entire cardiac output every minute, having the densest capillary bed in the body, and being the first reservoir of most lymphatic drainage entering the venous system. There are multiple postulated routes of metastasis to the pulmonary system including hematogenous and lymphatic routes with early or late dissemination. The vascularization of pulmonary metastases is variable and complex, often recruiting supply from bronchial and pulmonary origin. There are also many biochemical factors in the tumor microenvironment that play a key role in the development of lung metastases including vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), very late antigen 4 (VLA-4) and intercellular adhesion molecule 1 (ICAM-1). Studies vary widely in reported rates of pulmonary metastases due to differences in clinical study design, however, it is commonly accepted that up to half of autopsies performed on patients who died of malignancy have pulmonary metastases. In a surgical series describing the incidence of primary cancer types with resected pulmonary metastases the most common sites were thyroid, colon, breast, genitourinary tract, skin, liver, breast, and adrenal glands.

PMID:34012606 | PMC:PMC8107531 | DOI:10.21037/jtd.2020.04.28

Melanoma and Li-Fraumeni syndrome - family history not essential for screening recommendation

Fetched: May 20th, 2021, 5:00am GMT by H Regan

Clin Exp Dermatol. 2021 May 19. doi: 10.1111/ced.14748. Online ahead of print.

ABSTRACT

Li-Fraumeni Syndrome (LFS) is a recognised cancer predisposition syndrome associated with early onset of multiple cancer types. It was first described in 1969 following the identification of two soft tissue sarcomas in five families with the index case presenting with rhabdomyosarcoma in childhood.¹ The tumour spectrum classically includes a range of soft tissue sarcomas, bone tumours, haematological malignancies, breast cancer and adrenal cortical cancer.

PMID:34008262 | DOI:10.1111/ced.14748

Solitary castrate-resistant prostate cancer metastasis to adrenal gland with concordant intense avidity on PSMA and FDG PET

Fetched: May 20th, 2021, 5:00am GMT by Stephen McGeorge

Urol Case Rep. 2021 Apr 27;38:101696. doi: 10.1016/j.eucr.2021.101696. eCollection 2021 Sep.

ABSTRACT

Isolated prostate cancer metastasis to the adrenal gland is rare. We report a case of concordant high uptake in a solitary adrenal metastasis on both prostate-specific membrane antigen and fluorodeoxyglucose positron-emission tomography in a patient with castrate-resistant prostate cancer. Good initial biochemical response was achieved with laparoscopic adrenalectomy. The patient developed lymph node recurrence 12 months later, although remains asymptomatic on hormonal treatment 22 months post-operatively, in keeping with prior results for metastasis-directed therapy which can delay time to additional treatment. Application of dual tracer PET can be valuable for prostate cancer staging and guidance of metastasis-directed treatment.

PMID:34007790 | PMC:PMC8111578 | DOI:10.1016/j.eucr.2021.101696

Permalink for 'Integrative evaluation of primary and metastatic lesion spectrum to guide anti-PD-L1 therapy of non-small cell lung cancer: results from two randomized studies'

Integrative evaluation of primary and metastatic lesion spectrum to guide anti-PD-L1 therapy of non-small cell lung cancer: results from two randomized studies

Fetched: May 18th, 2021, 5:00am GMT by Si-Cong Ma

Oncoimmunology. 2021 Apr 26;10(1):1909296. doi: 10.1080/2162402X.2021.1909296.

ABSTRACT

Objectives: Clinical benefits of immune-checkpoint blockade (ICB) versus standard chemotherapy have been established in unselected non-small cell lung cancer (NSCLC). However, the response to ICB therapy among patients is heterogeneous in clinical practice. Materials and Methods: We retrospectively assessed the predicitive effect of the primary and metastatic lesion spectrum (baseline sum of the longest diameters [SLD], number of metastatic sites and specific organ metastases) on the efficacy of atezolizumab over docetaxel in OAK and POPLAR trial cohorts. A decision model, termed DSO (Diameter-Site-Organ), based on the spectrum was developed and validated for guiding ICB. Results: Higher SLD (>38 mm) and more metastatic sites (≥2) were characterized with pronounced overall survival (OS) benefits from atezolizumab versus docetaxel. Specifically, adrenal gland and brain metastases were identified as favorable predictors of atezolizumab treatment. The DSO model was developed in the discovery cohort to integrate the directive effect of the primary and metastatic lesion spectrum. Remarkably, a general pattern of enhanced efficacy of atezolizumab versus docetaxel was observed along with the increase of the DSO score. For patients with DSO score > 0, atezolizumab yielded a significantly prolonged OS than docetaxel, whereas OS was generally similar between two treatments in patients with DSO score ≤ 0. Equivalent findings were also seen in the internal and external validation cohorts. Conclusions: The response to anti-PD-L1 therapy among patients varied with the primary and metastatic lesion spectrum. The DSO-based system might provide promising medication guidance for ICB treatment in NSCLC patients.

PMID:33996262 | PMC:PMC8078693 | DOI:10.1080/2162402X.2021.1909296

Functional Malignant Retroperitoneal Paraganglioma with Liver Metastasis: a Rare Case Report

Fetched: May 18th, 2021, 5:00am GMT by Sachin S Kadam

Indian J Surg Oncol. 2021 Apr;12(Suppl 1):186-192. doi: 10.1007/s13193-020-01259-4. Epub 2021 Jan 5.

ABSTRACT

Paragangliomas are rare neoplasms. Their specific annual incidence is still unclear. These are rare neuroendocrine tumors which arise from extra-adrenal paraganglioma and they have the ability to secrete catecholamines. Most of them are diagnosed in the 3rd to 5th decades of life with mean age around 47 years. Majority of them are benign; however, malignant tumors with metastatic behavior are very rare. The incidence of malignant paraganglioma is estimated around 93/400 million people. The clinical course of metastatic malignant disease is variable and the reported 5-year survival is around 12-84%. There is no curative treatment option for malignant metastatic paraganglioma. If resectable, both, primary and metastasis should be resected. The only criteria which defines its malignancy is the presence of metastatic spread of chromaffin cells in tissues that normally do not contain such cells. Functional paraganglioma secretes excessive catecholamines which clinically manifest as paroxysmal hypertension, headache, sweating, and palpitations. We reported a case of young male who presented with huge left retroperitoneal mass and after evaluation found to have a functional malignant paraganglioma with liver metastasis. Surgical resection of the primary malignant paraganglioma with metastatectomy helps in decreasing the complications, improving the symptoms and prolonging the survival.

PMID:33994745 | PMC:PMC8119541 | DOI:10.1007/s13193-020-01259-4

Recurrent pheochromocytoma with catecholamine cardiomyopathy and left ventricular thrombus: a case report

Fetched: May 15th, 2021, 5:00am GMT by Renzheng Chen

J Int Med Res. 2021 Apr;49(4):3000605211007723. doi: 10.1177/03000605211007723.

ABSTRACT

Pheochromocytoma is a rare and usually benign tumor of the adrenal glands. We report a case of a 40-year-old woman with recurrent pheochromocytoma and catecholamine cardiomyopathy. She had no history of other types of tumors or connective tissue disease. She had already undergone surgery twice to remove the pheochromocytoma, which had now recurred for the second time. A thrombus in the left ventricle was also noted upon imaging examination, which dissipated after anticoagulation therapy using dabigatran, allowing the patient to opt for an elective third surgery. This paper describes the clinical outcome of using the anticoagulant dabigatran to treat left ventricular thrombosis in this rare case of recurrent pheochromocytoma, and thus further contributing to the knowledge of the clinical management of this rare and complicated disease.

PMID:33884914 | PMC:PMC8074535 | DOI:10.1177/03000605211007723

Primary Pulmonary Paraganglioma:Report of a Case

Fetched: May 15th, 2021, 5:00am GMT by Masahiro Abe

Kyobu Geka. 2021 Feb;74(2):160-163.

ABSTRACT

A 60-year-old woman with a lung tumor was admitted to our hospital for surgical treatment. Chest computed tomography (CT) showed a 23×21×20 mm nodule in the right lower lobe. Although the lung nodule was thought to be benign due to CT image findings, its size was apparently larger than that of CT image at four years ago. So, we decided to resect the nodule and performed a partial lung resection under video-assisted thoracic surgery. The tumor was histopathologically diagnosed as a paraganglioma and scored 0 point in pheochromocytoma of the adrenal gland score( PASS). Since no abnormal uptake that indicates primary site was not found on fluorodeoxyglucose-positron emission tomography (FDGPET) performed after surgery, we diagnosed this tumor as a primary pulmonary paraganglioma. She is still alive without recurrence.

PMID:33976026

Adrenal cavernous hemangioma misdiagnosed as pheochromocytoma: a case report

Fetched: May 15th, 2021, 5:00am GMT by Ting Huang

BMC Surg. 2021 Apr 26;21(1):210. doi: 10.1186/s12893-021-01195-2.

ABSTRACT

BACKGROUND: Adrenal hemangioma is a rare benign adrenal tumor that is usually misdiagnosed preoperatively. We here present a case of adrenal cavernous hemangioma that was successfully treated with retroperitoneal laparoscopic adrenalectomy.

CASE PRESENTATION: A 67-year-old man with dull right back pain attended our clinic for examination of a mass on the right adrenal gland for 1 week. Pheochromocytoma was considered according to the preoperative computed tomography angiography + computed tomography urography findings and was subsequently corrected to adrenal gland hemangioma according to postoperative pathological findings. The patient showed no recurrence of adrenal hemangioma during the 1-year follow-up period after surgery.

CONCLUSION: Adrenal gland hemangioma is rare with a high rate of misdiagnosis, and it should be considered in imaging findings of adrenal tumors with typical hemangioma. Surgery is an effective treatment method.

PMID:33902538 | PMC:PMC8074472 | DOI:10.1186/s12893-021-01195-2

Long-term opioid treatment and endocrine measures in chronic non-cancer pain patients: A systematic review and meta-analysis

Fetched: May 14th, 2021, 5:00am GMT by Pernille D K Diasso

Eur J Pain. 2021 May 13. doi: 10.1002/ejp.1797. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Long-term opioid treatment (L-TOT) of chronic non-cancer pain (CNCP) patients has been suspected to alter the endocrine system. This systematic review and meta-analysis aimed at investigating the published evidence of L-TOT effects on the endocrine system in adult CNCP patients.

DATABASES AND DATA TREATMENT: A systematic search of the literature in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and the CINAHL was performed. Studies examining measures of endocrine function of the hypothalamic-pituitary-gonadal, -adrenal, -thyroid, -somatotropic and -prolactin axis in adult CNCP patients in L-TOT (≥4 weeks of use) were included. Outcomes and the level of evidence were analyzed (The Cochrane Collaboration Tool, modified version of the Newcastle-Ottawa Scale and Rating of Recommendations Assessment, Development and Evaluation working group).

RESULTS: A total of 2660 studies were identified; 1981 excluded and finally thirteen studies (one randomized controlled trial (RCT), three longitudinal- and nine cross-sectional studies) were analyzed. L-TOT was associated with low insulin, suppression of the hypothalamic-pituitary-gonadal axis and alterations of the hypothalamic-pituitary-adrenal axis in both men and women with CNCP compared to different control groups (CNCP or healthy pain-free). No other significant differences were reported. The studies had a high risk of bias and the overall quality of evidence was low.

CONCLUSION: There seems to be an impact of L-TOT in CNCP patients on several components of the endocrine system, but the level of evidence is weak. Given the high prevalence of L-TOT use systematic studies of larger patient populations are urgently needed.

PMID:33982828 | DOI:10.1002/ejp.1797

Cytotoxic Effect of Progesterone, Tamoxifen and Their Combination in Experimental Cell Models of Human Adrenocortical Cancer

Fetched: May 14th, 2021, 5:00am GMT by Elisa Rossini

Front Endocrinol (Lausanne). 2021 Apr 26;12:669426. doi: 10.3389/fendo.2021.669426. eCollection 2021.

ABSTRACT

Progesterone (Pg) and estrogen (E) receptors (PgRs and ERs) are expressed in normal and neoplastic adrenal cortex, but their role is not fully understood. In literature, Pg demonstrated cytotoxic activity on AdrenoCortical Carcinoma (ACC) cells, while tamoxifen is cytotoxic in NCI-H295R cells. Here, we demonstrated that in ACC cell models, ERs were expressed in NCI-H295R cells with a prevalence of ER-β over the ER-α.Metastasis-derived MUC-1 and ACC115m cells displayed a very weak ER-α/β signal, while PgR cells were expressed, although at low level. Accordingly, these latter were resistant to the SERM tamoxifen and scarcely sensitive to Pg, as we observed a lower potency compared to NCI-H295R cells in cytotoxicity (IC50: MUC-1 cells: 67.58 µM (95%CI: 63.22-73.04), ACC115m cells: 51.76 µM (95%CI: 46.45-57.67) and cell proliferation rate. Exposure of NCI-H295R cells to tamoxifen induced cytotoxicity (IC50: 5.43 µM (95%CI: 5.18-5.69 µM) mainly involving ER-β, as their nuclear localization increased after tamoxifen: Δ A.U. treated vs untreated: 12 h: +27.04% (p < 0.01); 24 h: +36.46% (p < 0.0001). This effect involved the SF-1 protein reduction: Pg: -36.34 ± 9.26%; tamoxifen: -46.25 ± 15.68% (p < 0.01). Finally, in a cohort of 36 ACC samples, immunohistochemistry showed undetectable/low level of ERs, while PgR demonstrated a higher expression. In conclusion, ACC experimental cell models expressed PgR and low levels of ER in line with data obtained in patient tissues, thus limiting the possibility of a clinical approach targeting ER. Interestingly, Pg exerted cytotoxicity also in metastatic ACC cells, although with low potency.

PMID:33981288 | PMC:PMC8108132 | DOI:10.3389/fendo.2021.669426

Hypoglycemia in a Patient with Hypercortisolism and Adrenocortical Carcinoma: A Paradoxical Entity

Fetched: May 13th, 2021, 5:00am GMT by Sushmita Khadka

J Adolesc Young Adult Oncol. 2021 May 12. doi: 10.1089/jayao.2020.0229. Online ahead of print.

ABSTRACT

Adrenal cortical carcinoma is a rare and aggressive cancer with poor prognosis. Cases usually present with signs and symptoms of excessive hormone production. Hyperglycemia and Cushing syndrome are common, but tumor-associated hypoglycemia due to paraneoplastic secretion of insulin-like growth factor-2 (termed Anderson's syndrome) is uncommon. Given the rarity of adrenal cortical carcinoma, diagnosis and management of associated complications is challenging. In this study, we present a case of metastatic adrenal cortical carcinoma with a myriad of hormonal abnormalities. We will also briefly review literature regarding genetic association, pathophysiology, treatment options, and prognosis.

PMID:33978483 | DOI:10.1089/jayao.2020.0229

Permalink for 'Two Cases of Advanced Gastric Cancer with Para-Aortic Lymph Node Metastasis or Recurrence for Which Nivolumab Therapy Were Effective'

Two Cases of Advanced Gastric Cancer with Para-Aortic Lymph Node Metastasis or Recurrence for Which Nivolumab Therapy Were Effective

Fetched: May 13th, 2021, 5:00am GMT by Shinya Kidogami

Gan To Kagaku Ryoho. 2021 Apr;48(4):575-577.

ABSTRACT

A 74‒year‒old man was diagnosed with advanced gastric cancer with para‒aortic lymph node metastasis and ascites. He has been treated with S‒1 plus oxaliplatin as the primary treatment, paclitaxel plus ramucirumab as the secondary treatment and CPT‒11 as the third‒line treatment, but the effect of all treatments were temporary and left adrenal metastasis appeared during the course. Nivolumab was started as the fourth‒line treatment. Two months later, para‒aortic lymph nodes and left adrenal metastasis were markedly shrank and ascites disappeared. A 79 years old woman was performed proximal gastrectomy for advanced gastric cancer of the upper stomach. S‒1 therapy was started as adjuvant chemotherapy, but tumor markers have been increased and para‒aortic lymph node recurrence was observed 4 months after the operation. After ramucirumab as the primary treatment was ineffective, nivolumab was started as the secondary treatment. Two months later, para‒aortic lymph nodes shrank below the significant size and tumor markers were normalized.

PMID:33976053

Esophageal metastases from primary lung cancer: a case report

Fetched: May 13th, 2021, 5:00am GMT by Chang-Yong Wang

J Med Case Rep. 2021 May 12;15(1):265. doi: 10.1186/s13256-021-02765-x.

ABSTRACT

BACKGROUND: Primary lung cancer is one of the most frequently diagnosed cancers. The common metastatic sites are the liver, bones, brain, adrenal glands and central nervous system. However, gastrointestinal metastases, particularly esophageal metastases, from lung cancer are rare. There are no cases of esophageal metastases from lung cancer which refer to its particular treatment.

CASE PRESENTATION: We report a case of esophageal metastases from lung cancer. The patient was a 55-year-old Han Chinese man who first attended our hospital due to dry cough and was diagnosed with late-stage lung cancer. Three months later, the patient complained of dysphagia. Endoscopic ultrasonography (EUS) and pathological examination of the biopsy specimen was performed to confirm the lesion was metastases from lung cancer. Thyroid transcription factor 1 (TTF-1), cytokeratin 7 (CK-7) and napsin A were positive by immunohistochemistry examination. These results reconfirmed the diagnosis of esophageal metastases from lung cancer.

CONCLUSIONS: Esophageal metastasis from lung cancer is very rare. It may be alleviated with personalized chemotherapy. In addition, molecular targeted therapy for patients with epidermal growth factor receptor (EGFR) mutations may be reasonable.

PMID:33975638 | PMC:PMC8114513 | DOI:10.1186/s13256-021-02765-x

Association between pheochromocytoma and neurofibromatosis type I: a rare entity in the African population

Fetched: May 13th, 2021, 5:00am GMT by Brandon S Jackson

BMJ Case Rep. 2021 May 10;14(5):e238380. doi: 10.1136/bcr-2020-238380.

ABSTRACT

The association of pheochromocytoma in patients with neurofibromatosis type I has rarely been reported in low-income countries, especially on the African continent. A 43-year-old woman with neurofibromatosis type I was diagnosed with a right adrenal pheochromocytoma in Pretoria, South Africa. To our knowledge, this report is the first case to be published of a patient with neurofibromatosis type I diagnosed with a pheochromocytoma in Pretoria, and one of three cases on the African continent. The rarity may be due to the two associated conditions being under-reported, undiagnosed, misdiagnosed or possibly the association is rare on the African continent. The clinician dealing with these two conditions should be aware of the association.

PMID:33972293 | PMC:PMC8112419 | DOI:10.1136/bcr-2020-238380

Intestinal-type Adenocarcinoma Presenting as a Mandibular Mass: An Unusual Presentation

Fetched: May 11th, 2021, 5:00am GMT by Nouman Rashid

Contemp Clin Dent. 2021 Jan-Mar;12(1):99-101. doi: 10.4103/ccd.ccd_217_20. Epub 2021 Mar 20.

ABSTRACT

Intestinal-type adenocarcinoma is an aggressive malignancy with the rare possibility of metastatic spread to the mandible. We represent a case of a 30-year-old female patient who reported with a chief complaint of a right mandibular mass for 4 months. Orthopantomogram X-ray observed an ill-defined lytic lesion with severe periosteal reaction. Incisional biopsy revealed "colonic variant of intestinal-type adenocarcinoma." Expression of cytokeratin 20 and caudal type homeobox transcription factor 2 (CDX-2) markers was seen on immunohistochemistry. Biochemical markers such as serum cancer antigen 125, serum alkaline phosphatase, and serum carcinoembryonic antigen were raised. Contrast-enhanced computed tomography of the thorax and abdomen suggested cavitary lesions in the bilateral lungs, right adrenal gland, and mediastinum. Positron emission tomography revealed multiple lesions in the body, hence confirming the diagnosis. The patient was kept on palliative chemotherapy. It is concluded that prompt diagnosis and initiation of treatment increases the chances of survival in such cases.

PMID:33967548 | PMC:PMC8092088 | DOI:10.4103/ccd.ccd_217_20

Permalink for 'Phase I trial of intravesical Bacillus Calmette-Guerin combined with intravenous pembrolizumab in recurrent or persistent high-grade non-muscle-invasive bladder cancer after previous Bacillus Calmette-Guerin treatment'

Phase I trial of intravesical Bacillus Calmette-Guerin combined with intravenous pembrolizumab in recurrent or persistent high-grade non-muscle-invasive bladder cancer after previous Bacillus Calmette-Guerin treatment

Fetched: May 10th, 2021, 5:00am GMT by Shaheen Alanee

World J Urol. 2021 May 8. doi: 10.1007/s00345-021-03716-3. Online ahead of print.

ABSTRACT

OBJECTIVES: We conducted the first phase I dose-escalation trial (NCT02324582) of intravesical Bacillus Calmette-Guérin (BCG) in combination with systemic pembrolizumab in patients with high-grade non-muscle-invasive bladder cancer (HGNMIBC) who had persistent or recurrent disease after prior intravesical therapy with BCG. The primary endpoint was the safety of this combination. The secondary endpoint was clinical activity at three months following BCG treatment.

METHODS: Eighteen patients were consented for the study, five of which were screen failures. Six doses of pembrolizumab were administered every 3 weeks over 16 weeks concurrently with six weekly doses of BCG beginning at week 7. Patient safety was evaluated from the time of consent through 30 days following pembrolizumab treatment. Clinical activity was determined using cystoscopy and biopsy of suspicious lesions.

RESULTS: Treatment-related adverse events included one grade 4 adverse event (AEs) (adrenal insufficiency). There were nine grade 3 AEs (chest discomfort, pulmonary embolism, arthritis, wrist edema, injection site reaction, bilateral wrist pain, cardiomyopathy, hypokalemia, urinary tract infection). There were 49 grade 1 and 30 grade 2 AEs (88% of AEs). Eleven patients finished the treatment, and two patients died during the study. Of 13 patients treated, nine patients (69%) had no evidence of disease at 3 months following BCG treatment.

CONCLUSIONS: We report for the first time that combining BCG and pembrolizumab in treating HGNMIBC is safe allowing complete treatment of most patients. A phase III trial has opened to test the efficacy of this combination in HGNMIBC (KEYNOTE-676).

PMID:33966128 | DOI:10.1007/s00345-021-03716-3

Ischiorectal fossa metastasis from colon cancer: Case report of a rare entity and review of literature

Fetched: May 10th, 2021, 5:00am GMT by Areej Mohammed Alzamil

Int J Surg Case Rep. 2021 May;82:105912. doi: 10.1016/j.ijscr.2021.105912. Epub 2021 Apr 27.

ABSTRACT

INTRODUCTION AND IMPORTANCE: Colorectal cancer is one of the most common cancers both nationally and internationally. It commonly metastases to local lymph nodes, liver and lungs, with few reported cases of rare sites of metastasis such as adrenal glands, breast and skin.

CASE PRESENTATION: We report a 55-year-old-female admitted as case of large bowel obstruction and unintentional weight loss. Computed tomography scan of chest, abdomen and pelvis (CT CAP) showed sigmoid colon circumferential thickening with three lesions in the right hemi-liver. A laparoscopic diverting ileostomy followed by a colonoscopy showed a sigmoidal mass consistent with adenocarcinoma on histopathology. Hence, she received neoadjuvant chemotherapy followed by hepatectomy for the liver metastasis. Post-operatively CT CAP showed a newly developed right ischiorectal fossa (IRF) nodule along with newly developed porta hepatis lymph node. PET scan showed uptake in these two new lesions. Therefore, the patient underwent resection of the primary tumor, porta hepatis lymph node and right ischiorectal fossa nodule excision. The histopathology of the primary tumor came as moderately differentiated adenocarcinoma with both ischiorectal lesion and the porta hepatis nodule being positive for metastatic disease.

CLINICAL DISCUSSION & CONCLUSION: Ischiorectal fossa tumors are extremely rare with the majority being benign in origin. Nevertheless, the possibility of metastasis is there with no clear explanation regarding the pathway of how the metastatic cells can reach the IRF. Pre-operative diagnosis is important to determine the appropriate approach particularly if the mass is thought to be malignant. Further larger studies are needed to understand the pathway of metastasis to IRF.

PMID:33964711 | PMC:PMC8121690 | DOI:10.1016/j.ijscr.2021.105912

$Permalink for 'Patient with respiratory distress, facial oedema and refractory hypokalaemia'$

Patient with respiratory distress, facial oedema and refractory hypokalaemia

Fetched: May 9th, 2021, 5:00am GMT by Udara Dilrukshi Senarathne

BMJ Case Rep. 2021 May 7;14(5):e240330. doi: 10.1136/bcr-2020-240330.

ABSTRACT

Small cell lung carcinoma, when associated with co-occurrence of complications such as paraneoplastic syndrome and superior vena cava syndrome, poses a greater management challenge to the clinical team. We report a 56-year-old man who was eventually diagnosed with stage III small cell lung carcinoma, presenting with respiratory distress, facial and upper body oedema, proximal muscle weakness, hypokalaemia, new-onset hypertension and hyperglycaemia. His medical management was complicated by associated superior vena cava syndrome and Cushing's syndrome leading to refractory hypokalemia, immunosuppression and depression. Although the patient improved clinically and biochemically with the chemotherapy and other treatments, the development of neutropenic pneumonia led to his demise. This case highlights the importance of a multidisciplinary approach to achieve better patient care and the need for good clinical vigilance to identify possible humoral manifestations of aggressive malignancies such as small cell carcinoma of the lung to assist their early detection.

PMID:33962921 | PMC:PMC8108648 | DOI:10.1136/bcr-2020-240330

Permalink for 'Multidisciplinary practice guidelines for the diagnosis, genetic counseling and treatment of pheochromocytomas and paragangliomas'

Multidisciplinary practice guidelines for the diagnosis, genetic counseling and treatment of pheochromocytomas and paragangliomas

Fetched: May 8th, 2021, 5:00am GMT by R Garcia-Carbonero

Clin Transl Oncol. 2021 May 6. doi: 10.1007/s12094-021-02622-9. Online ahead of print.

ABSTRACT

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla and the sympathetic/parasympathetic neural ganglia, respectively. The heterogeneity in its etiology makes PPGL diagnosis and treatment very complex. The aim of this article was to provide practical clinical guidelines for the diagnosis and treatment of PPGLs from a multidisciplinary perspective, with the involvement of the Spanish Societies of Endocrinology and Nutrition (SEEN), Medical Oncology (SEOM), Medical Radiology (SERAM), Nuclear Medicine and Molecular Imaging (SEMNIM), Otorhinolaryngology (SEORL), Pathology (SEAP), Radiation Oncology (SEOR), Surgery (AEC) and the Spanish National Cancer Research Center (CNIO). We will review the following topics: epidemiology; anatomy, pathology and molecular pathways; clinical presentation; hereditary predisposition syndromes and genetic counseling and testing; diagnostic procedures, including biochemical testing and imaging studies; treatment including catecholamine blockade, surgery, radiotherapy and radiometabolic therapy, systemic therapy, local ablative therapy and supportive care. Finally, we will provide follow-up recommendations.

PMID:33959901 | DOI:10.1007/s12094-021-02622-9

Ectopic ACTH secretion from a metastatic gastric carcinoma with neuroendocrine component

Fetched: May 8th, 2021, 5:00am GMT by Annalisa Montebello

BMJ Case Rep. 2021 May 6;14(5):e240290. doi: 10.1136/bcr-2020-240290.

ABSTRACT

An elderly gentleman was admitted to hospital with severe hypokalaemia of 1.75mmol/L. A background of a recently diagnosed metastatic gastric carcinoma with a neuroendocrine component pointed towards the diagnosis of ectopic ACTH secretion causing this dangerous electrolyte imbalance. He was treated with aggressive potassium supplementation and the adrenal steroid synthesis blocker metyrapone to acutely control his Cushing's syndrome. Chemotherapy consisting of carboplatin/etoposide combination was initiated but unfortunately the patients' health deteriorated, and he died three months after his initial diagnosis. This case highlights the accelerated presentation of hypercortisolism due to ectopic ACTH secretion. It discusses the classification of neuroendocrine tumours and their varied prognosis depending on the underlying tumour grade. It emphasises the importance of having a multidisciplinary team to be able to care for two underlying pathologies simultaneously: both the severe hypercortisolism and his metastatic gastric tumour.

PMID:33958355 | PMC:PMC8103837 | DOI:10.1136/bcr-2020-240290

Commentary on Apparent Bilateral Adrenal Suppression

Fetched: May 7th, 2021, 5:00am GMT by Barry A Sacks

J Vasc Interv Radiol. 2021 May;32(5):666-667. doi: 10.1016/j.jvir.2021.01.276.

NO ABSTRACT

PMID:33933249 | DOI:10.1016/j.jvir.2021.01.276

Permalink for 'Outcome of Surgical Resection and Chemotherapy Versus Chemotherapy Alone for the Treatment of Isolated Primary Adrenal Lymphoma: A Retrospective Cohort Study of 16 Consecutive Patients'

Outcome of Surgical Resection and Chemotherapy Versus Chemotherapy Alone for the Treatment of Isolated Primary Adrenal Lymphoma: A Retrospective Cohort Study of 16 Consecutive Patients

Fetched: May 7th, 2021, 5:00am GMT by Giulio Illuminati

Anticancer Res. 2021 May;41(5):2647-2652. doi: 10.21873/anticanres.15045.

ABSTRACT

BACKGROUND/AIM: Primary adrenal lymphoma (PAL) is rare and aggressive. The aim of this retrospective study was to compare the results of surgery and chemotherapy compared to chemotherapy alone for the treatment of this condition.

PATIENTS AND METHODS: Sixteen patients, 10 men and 6 women of a median age of 63 years (IQR=56-70.5 years), admitted for the treatment of PAL, were retrospectively reviewed. Six patients (37.5%) underwent surgical resection of the mass followed by CHOP (cyclophosphamide, doxorubicin, vincristine, bleomycin and prednisone) - based chemotherapy (Group A). Ten patients (62.5%) underwent chemotherapy alone, consisting of CHOP alone in one case and Rituximab-CHOP (R-CHOP) in 9 cases (Group B). As primary study endpoints of the study, overall survival (OS) and progression-free survival (PFS) were considered.

RESULTS: At two years follow-up, OS was 50% in Group A and 60% in group B (p=0.69). The PFS was 50% in group A and 30% in group B (p=0.42).

CONCLUSION: PAL exhibits overall a dismal prognosis. Chemotherapy remains the most appropriate treatment, although unable to ensure long-term survival. Surgery combined with chemotherapy is ineffective in improving survival and may, at best, have a limited role in relieving the pain related to the local mass effect.

PMID:33952495 | DOI:10.21873/anticanres.15045

Epidemiological profile of dermatomyositis and polymyositis: a study conducted in the Department of Rheumatology in Marrakech

Fetched: May 6th, 2021, 5:00am GMT by Souhil Errafia

Pan Afr Med J. 2021 Jan 29;38:101. doi: 10.11604/pamj.2021.38.101.25406. eCollection 2021.

ABSTRACT

Dermatomyositis (DM) and polymyositis (PM) are rare but serious conditions. The purpose of this study was to investigate, by a review of hospital cases, their epidemiological, clinical and evolutionary profile. We conducted a retrospective study over a 15-year period, between January 2004 and December 2019. All cases with possible or definite diagnosis according to Bohan and Peter's criteria were retained. A total of 14 patients were enrolled (8 DM and 6 PM), with an average age of 48.7 years. Sex ratio was 13F/ 1H. General signs were reported in 71% of cases. Motor deficit affected the girdle muscles in 71% of cases; 85.7% of patients had arthralgia and 14% arthritis. Erythema and periorbital edema were the predominant skin signs. Patients' assessment showed increased sedimentation rate in all cases and increased muscle enzymes in 80% of cases. Antinuclear antibodies were positive in 63% of cases. Muscle biopsy objectified inflammatory myositis in 75% of cases. Heart disease was reported in 14% of cases and lung disease in 21%. Cancer was found in 21.4% of cases. All patients received corticosteroid therapy. Improvement was reported in 88% of patients, with a relapse in 4 patients. In our context, DM is more frequent than PM, with a clear female predominance. Pulmonary disease is a heavy complication. Its association with cancers occurs commonly, hence the need for a systematic cancer screening at diagnosis and follow-up.

PMID:33889267 | PMC:PMC8035687 | DOI:10.11604/pamj.2021.38.101.25406

The embryonic ontogeny of the gonadal somatic cells in mice and monkeys

Fetched: May 6th, 2021, 5:00am GMT by Kotaro Sasaki

Cell Rep. 2021 May 4;35(5):109075. doi: 10.1016/j.celrep.2021.109075.

ABSTRACT

In the early fetal stage, the gonads are bipotent and only later become the ovary or testis, depending on the genetic sex. Despite many studies examining how sex determination occurs from biopotential gonads, the spatial and temporal organization of bipotential gonads and their progenitors is poorly understood. Here, using lineage tracing in mice, we find that the gonads originate from a T⁺ primitive streak through WT1⁺ posterior intermediate mesoderm and appear to share origins anteriorly with the adrenal glands and posteriorly with the metanephric mesenchyme. Comparative single-cell transcriptomic analyses in mouse and cynomolgus monkey embryos reveal the convergence of the lineage trajectory and genetic programs accompanying the specification of biopotential gonadal progenitor cells. This process involves sustained expression of epithelial genes and upregulation of mesenchymal genes, thereby conferring an epithelial-mesenchymal hybrid state. Our study provides key resources for understanding early gonadogenesis in mice and primates.

PMID:33951437 | DOI:10.1016/j.celrep.2021.109075

Permalink for 'Infantile Rhabdomyosarcomas With VGLL2 Rearrangement Are Not Always an Indolent Disease: A Study of 4 Aggressive Cases With Clinical, Pathologic, Molecular, and Radiologic Findings'

Infantile Rhabdomyosarcomas With VGLL2 Rearrangement Are Not Always an Indolent Disease: A Study of 4 Aggressive Cases With Clinical, Pathologic, Molecular, and Radiologic Findings

Fetched: May 6th, 2021, 5:00am GMT by Joanna Cyrta

Am J Surg Pathol. 2021 Jun 1;45(6):854-867. doi: 10.1097/PAS.0000000000001702.

ABSTRACT

VGLL2-rearranged rhabdomyosarcomas (RMS) are rare low-grade tumors with only favorable outcomes reported to date. We describe 4 patients with VGLL2-rearranged RMS confirmed by molecular studies, who experienced local progression and distant metastases, including 2 with fatal outcomes. Tumors were diagnosed at birth (n=3) or at 12 months of age (n=1), and were all localized at initial diagnosis, but unresectable and therefore managed with chemotherapy and surveillance. Metastatic progression occurred from 1 to 8 years from diagnosis (median, 3.5 y). Three patients experienced multimetastatic spread and one showed an isolated adrenal metastasis. At initial diagnosis, 3 tumors displaying bland morphology were misdiagnosed as fibromatosis or infantile fibrosarcoma and initially managed as such, while 1 was a high-grade sarcoma. At relapse, 3 tumors showed high-grade morphology, while 1 retained a low-grade phenotype. Low-grade primary tumors showed only very focal positivity for desmin, myogenin, and/or MyoD1, while high-grade tumors were heterogenously or diffusely positive. Whole-exome sequencing, performed on primary and relapse samples for 3 patients, showed increased genomic instability and additional genomic alterations (eg, TP53, CDKN2A/B, FGFR4) at relapse, but no recurrent events. RNA sequencing confirmed that high-grade tumors retained VGLL2 fusion transcripts and transcriptomic profiles consistent with VGLL2-rearranged RMS. High-grade samples showed a high expression of genes encoding cell cycle proteins, desmin, and some developmental factors. These 4 cases with distinct medical history imply the importance of complete surgical resection, and suggest that RMS-type chemotherapy should be considered in unresectable cases, given the risk of high-grade transformation. They also emphasize the importance of correct initial diagnosis.

PMID:33949344 | DOI:10.1097/PAS.0000000000001702

Adrenocortical Carcinoma: A Case of Missed Diagnosis

Fetched: May 6th, 2021, 5:00am GMT by Yusef Hazimeh

Cureus. 2021 Apr 1;13(4):e14235. doi: 10.7759/cureus.14235.

ABSTRACT

Incidentalomas are commonly encountered adrenal lesions. However, adrenocortical carcinoma (ACC) represents a rare etiology of adrenal incidentalomas (AI). The diagnosis of AI is generally based on laboratory data and imaging results, Fine needle aspiration (FNA) is not usually indicated in the workup of incidentaloma. In this report, we present a case of AI in which two FNA procedures failed to make the correct diagnosis of ACC.

PMID:33948420 | PMC:PMC8087872 | DOI:10.7759/cureus.14235

Permalink for 'GIPC2 is an endocrine-specific tumor suppressor gene for both sporadic and hereditary tumors of RET- and SDHB-, but not VHL-associated clusters of pheochromocytoma/paraganglioma'

GIPC2 is an endocrine-specific tumor suppressor gene for both sporadic and hereditary tumors of RET- and SDHB-, but not VHL-associated clusters of pheochromocytoma/paraganglioma

Fetched: May 6th, 2021, 5:00am GMT by Yeqing Dong

Cell Death Dis. 2021 May 4;12(5):444. doi: 10.1038/s41419-021-03731-7.

ABSTRACT

Pheochromocytoma/paraganglioma (PPGL) is an endocrine tumor of the chromaffin cells in the adrenal medulla or the paraganglia. Currently, about 70% of PPGLs can be explained by germline or somatic mutations in several broadly expressed susceptibility genes including RET, VHL, and SDHB, while for the remaining, mainly sporadic cases, the pathogenesis is still unclear. Even for known susceptible genes, how mutations in these mostly ubiquitous genes result in tissue-specific pathogenesis remains unanswered, and why RET-mutated tumors almost always occur in the adrenal while SDHB-mutated tumors mostly occur extra-adrenal remains a mystery. By analyzing 22 sporadic PPGLs using SNP 6.0 genotyping arrays combined with expression profiling of 4 normal and 4 tumor tissues, we identified GIPC2, a gene located at 1p31.1 with preferential expression in adrenal and inducible by adrenal glucocorticoid, as a novel putative tumor suppressor gene for PPGLs. Copy number deletion and GIPC2 promoter hypermethylation but not GIPC2 mutation, accompanied with reduced GIPC2 expression, were observed in 39 of 55 PPGLs in our cohort. Examination of a published expression database consisting of 188 PPGLs found little GIPC2 expression in Cluster 1A (SDHx-associated) and Cluster 2A (NF1/RET-associated) tumors, but less pronounced reduction of GIPC2 expression in Cluster 1B (VHL-associated) and Cluster 2B/2C tumors. GIPC2 induced p27, suppressed MAPK/ERK and HIF-1ɑ pathways as well as cancer cell proliferation. Overexpressing GIPC2 in PC12 cells inhibited tumor growth in nude mice. We found GIPC2 interacted with the nucleoprotein NONO and both proteins regulated p27 transcription through the same GGCC box on p27 promoter. Significantly, low expression of both GIPC2 and p27 was associated with shorter disease-free survival time of PPGLs patients in the TCGA database. We found that PPGL-causing mutations in RET and in SDHB could lead to primary rat adrenal chromaffin cell proliferation, ERK activation, and p27 downregulation, all requiring downregulating GIPC2. Notably, the RET-mutant effect required the presence of dexamethasone while the SDHB-mutant effect required its absence, providing a plausible explanation for the tumor location preference. In contrast, the PPGL-predisposing VHL mutations had no effect on proliferation and GIPC2 expression but caused p53 downregulation and reduced apoptosis in chromaffin cells compared with wild-type VHL. Thus, our study raises the importance of cortical hormone in PPGL development, and GIPC2 as a novel tumor suppressor provides a unified molecular mechanism for the tumorigenesis of both sporadic and hereditary tumors of Clusters 1A and 2A concerning SDHB and RET, but not tumors of Cluster 1B concerning VHL and other clusters.

PMID:33947839 | PMC:PMC8096975 | DOI:10.1038/s41419-021-03731-7

Bladder paraganglioma: Report of two cases and a literature review.

Fetched: May 6th, 2021, 5:00am GMT by Francisco J Pelegrín-Mateo

Arch Esp Urol. 2021 May;74(4):445-449.

ABSTRACT

OBJECTIVE: Description of two incidental cases of bladder paraganglioma in women and review of the published literature.

METHODS: A bibliographic search was carried out in Medline over the last 10 years according to the terms "urinary bladder" and "paraganglioma".

RESULTS: Bladder paraganglioma (BP) accounts for less than 0.06% of bladder tumors and 10% of all paragangliomas. It may be sporadic or associated with hereditary predisposition syndromes such as Hereditary Paraganglioma- Pheochromocytoma Syndrome. Due to its rarity, there are no recommendations for treatment and monitoring but, their risk of malignancy forces a long-term follow up. The study of germinal mutations through massive sequencing ruled out the association with a hereditary syndrome. Initial management included early reassessment by cystoscopy, transurethral bladder resection (TURB) and imaging.

CONCLUSIONS: Bladder paragangliomas are rare tumors that can be associated to hereditary syndromes. Its treatment and follow - up must be based on a multidisciplinary approach.

PMID:33942738

Physiology of the Hypothalamic-Pituitary-Thyroid Axis

Fetched: May 5th, 2021, 5:00am GMT by Stefano Mariotti

2021 Apr 20. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, Dungan K, Grossman A, Hershman JM, Hofland J, Kalra S, Kaltsas G, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, McGee EA, McLachlan R, Morley JE, New M, Purnell J, Sahay R, Singer F, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–.

ABSTRACT

The activity of the thyroid gland is predominantly regulated by the concentration of the pituitary glycoprotein hormone, thyroid-stimulating hormone (TSH). In the absence of the pituitary or of thyrotroph function, hypothyroidism ensues. Thus, regulation of thyroid function in normal individuals is to a large extent determined by the factors which regulate the synthesis and secretion of TSH. Those factors are reviewed in this chapter and consist principally of thyrotropin-releasing hormone (TRH) and the feedback effects of circulating thyroid hormones at the hypothalamic and pituitary levels. The consequence of the dynamic interplay of these two dominant influences on TSH secretion, the positive effect of TRH on the one hand and the negative effects of thyroid hormones on the other, results in a remarkably stable morning concentration of TSH in the circulation and consequently little alteration in the level of circulating thyroid hormones from day to day and year to year. This regulation is so carefully maintained that an abnormal serum TSH in most patients is believed to indicate the presence of a disorder of thyroid gland function. The utility of TSH measurements has been recognized and its use has remarkably increased due to the development of immunometric methodologies for its accurate quantitation in serum, although the criteria to define a “normal range” still remain a matter of controversy. This chapter is organized into two general sections. The first portion reviews basic studies of TSH synthesis, post-translational modification, and release. The second deals with physiological studies in humans which serve as the background for the diagnostic use of TSH measurements and reviews the results of TSH assays in pathophysiological disorders. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:25905193 | Bookshelf:NBK278958

Primary Hyperparathyroidism

Fetched: May 5th, 2021, 5:00am GMT by Marcella D. Walker

2021 Apr 19. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, Dungan K, Grossman A, Hershman JM, Hofland J, Kalra S, Kaltsas G, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, McGee EA, McLachlan R, Morley JE, New M, Purnell J, Sahay R, Singer F, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–.

ABSTRACT

Primary hyperparathyroidism (PHPT) is characterized by hypercalcemia and elevated or inappropriately normal parathyroid hormone (PTH) levels. PHPT results from excessive secretion of PTH from one or more of the parathyroid glands. The clinical presentation of PHPT has evolved since the 1970’s with the advent of the routine measurement of serum calcium at that time. Classical PHPT, with its associated severe hypercalcemia, osteitis fibrosa cystica, nephrolithiasis, and neuropsychological symptoms, once common is now infrequent. Today most patients are asymptomatic and have mild hypercalcemia, but may have evidence of subclinical skeletal and renal sequelae such as osteoporosis and hypercalciuria as well as vertebral fractures and nephrolithiasis both of which may be asymptomatic. Parathyroidectomy is the only curative treatment for PHPT and is recommended in patients with symptoms and those with asymptomatic disease who have evidence of end-organ sequelae. Parathyroidectomy results in an increase in BMD and a reduction in nephrolithiasis. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:25905161 | Bookshelf:NBK278923

Diabetes Mellitus and Tuberculosis

Fetched: May 5th, 2021, 5:00am GMT by Sudeep Krishna

2021 Apr 18. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, Dungan K, Grossman A, Hershman JM, Hofland J, Kalra S, Kaltsas G, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, McGee EA, McLachlan R, Morley JE, New M, Purnell J, Sahay R, Singer F, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–.

ABSTRACT

The converging epidemics of non-communicable disease like DM (DM) and an infectious disease like tuberculosis (TB) is a double burden. DM is increasing in the same population that is at high risk for developing TB. There is a two-to-four-fold higher risk of active TB in individuals with DM and up to 30% of individuals with TB are likely to have DM. Immune deficiency either in absolute or relative quantities are sufficient for re-activation of latent TB. From a 10% risk of reactivation over the whole lifetime of an immunocompetent individual, the risk of reactivation increases to 10% every year in immune-deficient individuals. DM impairs cell mediated immunity and poor glycemic control affects cytokine response and alters the defenses in the alveolar macrophages. Fever, hemoptysis, extensive parenchymal lesions, and lung cavities are more common in those with DM particularly heavier and older males. DM increases the risk of treatment failure, death, and relapse. Evidence collected from meta-analysis conclude that DM can increase the odds of developing Multi Drug resistant TB (MDR-TB). The synergism between DM and TB necessitates bi-directional screening. Sputum examination for Ziehl-Neelsen staining is both a sensitive and specific screening test. Rapid molecular diagnostic tests like cartridge based nucleic acid amplification tests (CB-NAAT) are useful in cases where there is a high-index of suspicion and difficulty in arriving at a definitive diagnosis exists. Random plasma glucose and HbA1c (glycosylated Hemoglobin) measurements are convenient tests for DM screening that can be done in non-fasting individuals. Screening for DM more than once during the course of illness is sensible so that transient DM and new-onset DM can be identified. Anti-TB drugs affect glycemic control as they interact with anti-diabetic drugs by either stimulating or inhibiting the metabolizing enzymes. They may also aggravate metabolic, ocular, and neuropathic complications of DM. Insulin is the preferred drug in most instances. The presence of renal and hepatic dysfunction affects TB and hyperglycemic management. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:33945243 | Bookshelf:NBK570126

The Effect of Diet on Cardiovascular Disease and Lipid and Lipoprotein Levels

Fetched: May 5th, 2021, 5:00am GMT by Kenneth R. Feingold

2021 Apr 16. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, Dungan K, Grossman A, Hershman JM, Hofland J, Kalra S, Kaltsas G, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, McGee EA, McLachlan R, Morley JE, New M, Purnell J, Sahay R, Singer F, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–.

ABSTRACT

The role of lipids and lipoproteins as causal factors for cardiovascular disease (CVD) is well established. Dietary saturated fatty acids (SFA), which are in milk, butter, cheese, beef, lamb, pork, poultry, palm oil, and coconut oil increase LDL-C and HDL-C. The increase in LDL-C is due to a decrease in hepatic LDL clearance and an increase in LDL production secondary to a decrease in hepatic LDL receptors. Monounsaturated fatty acids (MUFA) are in olive, canola, peanut, safflower, and sesame oil, and avocados, peanut butter, and many nuts and seeds and polyunsaturated fatty acids (PUFA) are in soybean, corn, and sunflower oil, and some nuts and seeds, tofu, and soybeans. Both MUFA and PUFA lower LDL-C by increasing hepatic LDL receptor activity. Dietary cholesterol is found in egg yolks, shrimp, beef, pork, poultry, cheese, and butter and increase LDL-C but the effect is modest and varies with approximately 15-25% of individuals being hyper-responders with more robust increases. Dietary cholesterol reduces hepatic LDL receptor activity, decreasing the clearance and increasing the production of LDL. Trans fatty acids (TFA) occur naturally in meat and dairy products and are formed during the partial hydrogenation of vegetable fat. TFA increase LDL-C and decrease HDL-C. Carbohydrates (CHO) can be divided into high-quality, for example fruits, legumes, vegetables, and whole grains, or low-quality, which include refined grains, starches, and added sugars. CHO increase TG with low quality CHO, particularly added sugars, having a more robust effect. Dietary CHO, particularly fructose, promotes hepatic de novo fatty acid synthesis leading to increased VLDL secretion. Fiber is found mostly in fruits, vegetables, whole and unrefined grains, nuts, seeds, beans, and legumes and phytosterols are naturally occurring constituents of plants and are found in vegetable oils, cereals, nuts, fruit and vegetables. Both dietary fiber and phytosterols decrease LDL-C by decreasing intestinal cholesterol absorption.

With regards to CVD there are very few well conducted randomized controlled trials and most of the information is derived from observational studies that demonstrate associations. These observational studies have found that fruits, vegetables, beans/legumes, nuts/seeds, whole grains, fish, yogurt, fiber, seafood omega-3 fatty acids, and polyunsaturated fats were associated with a decreased risk of CVD while unprocessed red meats, processed meats, sugar-sweetened beverages, high glycemic load CHO, and trans-fats were associated with an increased risk of CVD. Randomized trials have shown that a Mediterranean diet reduces CVD. Based on this information current guidelines for the general population recommend 1. A diet emphasizing intake of vegetables, fruits, legumes, nuts, whole grains, and fish 2. Replacement of SFA with MUFA and PUFA 3. A reduced amount of dietary cholesterol 4. Minimizing intake of processed meats, refined CHO, and sweetened beverages and 5. Avoidance of TFA. For individuals with a high LDL-C limiting dietary SFA, TFA, and cholesterol and increasing fiber and phytosterols will help lower LDL-C while in individuals with high TG limiting low quality CHO, particularly simple sugars, and ethanol with weight loss, if indicated, will help lower TG. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:33945244 | Bookshelf:NBK570127

Autoimmune Polyglandular Syndromes

Fetched: May 5th, 2021, 5:00am GMT by Mark A. Sperling

2021 Apr 10. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, Dungan K, Grossman A, Hershman JM, Hofland J, Kalra S, Kaltsas G, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, McGee EA, McLachlan R, Morley JE, New M, Purnell J, Sahay R, Singer F, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–.

ABSTRACT

The autoimmune polyglandular syndromes (APS) are clusters of endocrine abnormalities that occur in discreet patterns in subjects with immune dysregulation and that permit treatment and anticipation of associated systemic or other hormonal deficiencies. Three major entities are recognized, APS1, APS2 and APS3; the rare X-linked syndrome of immunodysregulation, polyendocrinopathy, and enteropathy due to mutations in the FOXP3 gene also qualifies as an APS. An additional increasingly described category occurs in patients treated with immunoregulatory agents such as checkpoint inhibitors for cancer, so that tumor antigens that have evaded recognition can now be targeted, but at the expense of activating autoimmunity. APS1 is a syndrome characterized by chronic muco-cutaneous candidiasis, hypoparathyroidism, and primary adrenal insufficiency, as well as ectodermal dystrophy and a host of other endocrine and non-endocrine tissue involvement in autoimmune destructive processes. The underlying cause is a homozygous inactivating mutation in the autoimmune regulator gene AIRE which permits the intra-thymic expression of ectopic antigens normally expressed only in specific peripheral tissues (e.g., insulin), so that T-cells as they mature within the thymus and acquire a receptor for the self- antigen are eliminated (negative selection), thereby avoiding autoimmunity. Recent studies demonstrate that in addition to the classical homozygous mutations, single gene dominant mutations in AIRE play an important role in autoimmune regulation and its disorders. APS2 and APS3 are both due to mutations in the HLA DQ/DR regions which regulate antigen presentation to T-cell receptors; however, their genetic profile is more complex. APS2 is characterized by type 1 diabetes mellitus (T1DM), Addison Disease, and Hypothyroidism, whereas APS3 is similar but without Addison disease. In keeping with other autoimmune disorders, these entities are more frequent in females, whereas APS1 has no sexual predominance. The recent emergence of autoimmune endocrinopathies in patients treated with immunoregulatory agents for cancer adds a new dimension to considerations of autoimmune polyendocrinopathy syndromes. Rapid progress in the immunology and genetics of these entities offers the promise of potential amelioration and eventual reversal via genetic manipulation before organ damage is established. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:25905375 | Bookshelf:NBK279152

Lymphoma involving the brain and adrenals: A chicken and egg situation

Fetched: May 5th, 2021, 5:00am GMT by Tehreem Zafar

J Pak Med Assoc. 2021 Feb;71(2(B)):778.

ABSTRACT

Primary cerebellar diffuse large B-cell lymphoma (DLBCL) is a rare entity, which manifests with neurological symptoms. It is aggressive in nature with high rate of recurrence and short survival period. It commonly presents with local invasion and rarely spreads outside the central nervous system. Chemotherapy with radiation is the preferred treatment; however, surgery can be done for solitary lesions. Likewise, adrenal lymphoma as primary site of disease is rare but can present as extra-nodal disease. We present an unusual case of cerebellar DLBCL with bilateral adrenal involvement detected incidentally on 18-Fluorodeoxyglucose positron emission tomography (18F FDG PET-CT) scan.

PMID:33941982

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

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

China Adrenal Disease Registry

Posted: May 18th, 2021, 2:00pm GMT

Conditions: Cushing Syndrome; Aldosteronism; Hypoadrenalism; Congenital Adrenal Hyperplasia; Adrenal Adenoma; Adrenal Incidentaloma; Adrenal Carcinoma; Pheochromocytoma
Intervention:
Sponsor: Shanghai Jiao Tong University School of Medicine
Not yet recruiting

Research on the Effectiveness and Safety of Remote Control of Domestic Surgical Robot System for Urinary Surgery

Posted: March 18th, 2021, 2:00pm GMT

Natural History Study of Children and Adults With Adrenocortical Cancer (ACC)

Posted: June 25th, 2020, 2:00pm GMT

Conditions: Adrenocortical Carcinoma; Adrenocortical Cancer
Intervention:
Sponsor: National Cancer Institute (NCI)
Recruiting

Permalink for 'Study of Relacorilant in Combination With Pembrolizumab for Patients With Adrenocortical Carcinoma With Excess Glucocorticoid Production'

Study of Relacorilant in Combination With Pembrolizumab for Patients With Adrenocortical Carcinoma With Excess Glucocorticoid Production

Posted: May 4th, 2020, 2:00pm GMT

Condition: Adrenocortical Carcinoma
Interventions: Drug: Relacorilant; Drug: Pembrolizumab
Sponsor: Corcept Therapeutics
Recruiting

Mitotane With or Without Cisplatin and Etoposide After Surgery in Treating Participants With Stage I-III Adrenocortical Cancer With High Risk of Recurrence (ADIUVO-2)

Posted: July 11th, 2018, 2:00pm GMT

Nivolumab Combined With Ipilimumab for Patients With Advanced Rare Genitourinary Tumors

Posted: November 7th, 2017, 3:00pm GMT

Familial Investigations of Childhood Cancer Predisposition

Posted: February 10th, 2017, 3:00pm GMT

Adrenal Tumors - Pathogenesis and Therapy

Posted: April 30th, 2008, 2:00pm GMT

Preclinical Study Towards an Immunotherapy in Adrenocortical Carcinoma

Posted: April 6th, 2007, 2:00pm GMT

Conditions: Adrenocortical Carcinoma; Cushing's Syndrome
Intervention:
Sponsors: University of Wuerzburg; Deutsche Krebshilfe e.V., Bonn (Germany)
Recruiting

German Adrenocortical Carcinoma Registry

Posted: March 29th, 2007, 2:00pm GMT

Condition: Adrenocortical Carcinoma
Intervention:
Sponsors: University of Wuerzburg; Deutsche Krebshilfe e.V., Bonn (Germany)
Recruiting

Combination of mitotane and locoregional treatments in low-volume metastatic adrenocortical carcinoma

Fetched: June 19th, 2021, 5:00am GMT by Alice Boileve

J Clin Endocrinol Metab. 2021 Jun 18:dgab449. doi: 10.1210/clinem/dgab449. Online ahead of print.

ABSTRACT

PURPOSE: European and French guidelines for ENSAT stage IV low tumor burden or indolent adrenocortical carcinoma (ACC) recommend combination of mitotane and locoregional treatments (LRT) in first-line. Nevertheless, the benefit of LRT combination with mitotane has never been evaluated in this selected group of patients.

METHODS: A retrospective chart review was performed from 2003-2018 of patients with stage IV ACC with ≤2 tumoral organs who received mitotane in our center. Primary endpoint was the delay between mitotane initiation and first systemic chemotherapy. Secondary endpoints were progression-free survival (PFS) and overall survival (OS) from mitotane initiation. Adjusted analyses were performed on the main prognostic factors.

RESULTS: Out of 79 included patients, 48 (61%) patients were female and median age at stage IVA diagnosis was 49.8 years (interquartile-range:38.8-60.0). Metastatic sites were mainly lungs (76%) and liver (48%). Fifty-eight (73%) patients received LRT including adrenal bed radiotherapy (14 patients, 18%), surgery (37 patients, 47%) and/or interventional radiology n(35,44%). Median time between mitotane initiation and first chemotherapy administration was 9 months (Interquartile-range:4-18). Median PFS1 (first tumor-progression) was 6.0 months (CI95%:4.5-8.6). Median OS was 46 months (CI95%:41-68). PFS1, PFS2 and OS were statistically longer in the mitotane plus LRT group compared to the mitotane-only group (Hazard ratio (HR)=0.39 (CI95%:0.22-0.68), HR=0.35 (CI95%:0.20-0.63) and HR=0.27 (CI95%:0.14-0.50) respectively). Ten (13%) patients achieved complete response, all from mitotane plus LRT group.

CONCLUSION: Our results endorse European and French guidelines for stage IV ACC with ≤2 tumor-organs and favor the combination of mitotane and LRT as first-line treatment. For the first time, a significant number of complete responses were observed. Prospective studies are expected to confirm these findings.

PMID:34143888 | DOI:10.1210/clinem/dgab449

Effects of Sorafenib, a Tyrosin Kinase Inhibitor, on Adrenocortical Cancer

Fetched: June 11th, 2021, 5:00am GMT by Lidia Cerquetti

Front Endocrinol (Lausanne). 2021 May 24;12:667798. doi: 10.3389/fendo.2021.667798. eCollection 2021.

ABSTRACT

PMID:34108938 | PMC:PMC8183165 | DOI:10.3389/fendo.2021.667798

Permalink for '"You cannot expect miracles to happen overnight": patience pays off when you wish to establish a new adrenocortical carcinoma cell line'

"You cannot expect miracles to happen overnight": patience pays off when you wish to establish a new adrenocortical carcinoma cell line

Fetched: June 8th, 2021, 5:00am GMT by Enzo Lalli

Eur J Endocrinol. 2021 Jun 1:EJE-21-0389. doi: 10.1530/EJE-21-0389. Online ahead of print.

ABSTRACT

Growing attention is being paid to association of adrenocortical carcinoma (ACC), a rare endocrine malignancy, to cancer predisposition syndromes caused by germline mutations in genes involved in the control of genome stability. Tumour cells with a defective DNA mismatch repair pathway have a high mutation burden, which results in the production of tumour-associated specific neoantigens and in an increase of the sensitivity to therapies that loosen the constraints of tumour attack by the immune system. The study by Landwehr et al. published in the current issue of the European Journal of Endocrinology describes a patient with an aggressive ACC bearing a germline MUTYH mutation with loss of heterozygosity in the tumour and accumulation of 8-hydroxyguanine in its genomic DNA. The authors managed to establish a novel differentiated cell line from that tumour which bears the stigma of the defective DNA repair mechanism in its genome. The availability of this new cell model inside the expanding toolbox of the ACC cell lines will allow for novel experimental possibilities, in particular for the study of the tumour microenvironment and the response to immunotherapy.

PMID:34096882 | DOI:10.1530/EJE-21-0389

Adrenal Rests in the Uro-genital Tract of an Adult Population

Fetched: June 8th, 2021, 5:00am GMT by Enrico Costantino Falco

Endocr Pathol. 2021 Jun 7. doi: 10.1007/s12022-021-09685-y. Online ahead of print.

ABSTRACT

PMID:34095993 | DOI:10.1007/s12022-021-09685-y

Prognostic and Immunological Role of mRNA ac4C Regulator NAT10 in Pan-Cancer: New Territory for Cancer Research?

Fetched: June 8th, 2021, 5:00am GMT by Chuanxi Yang

Front Oncol. 2021 May 19;11:630417. doi: 10.3389/fonc.2021.630417. eCollection 2021.

ABSTRACT

BACKGROUND: NAT10 (also known as human N-acetyltransferase-like protein) is a critical gene that regulates N4-acetylcytidine formation in RNA, similar to the multiple regulators of N6-methyladenosine. However, the underlying functions and mechanisms of NAT10 in tumor progression and immunology are unclear.

METHODS: In this study, we systematically analyzed the pan-cancer expression and correlations of NAT10, using databases including Oncomine, PrognoScan, GEPIA2, and Kaplan-Meier Plotter. The potential correlations of NAT10 with immune infiltration stages and gene marker sets were analyzed using the Tumor Immune Estimation Resource and GEPIA2.

RESULTS: Compared with normal tissues, NAT10 showed higher expression in most cancers based on combined data from TCGA and GTEx. In different datasets, high NAT10 expression was significantly correlated with poor prognosis in adrenocortical carcinoma, head and neck squamous cell carcinoma, liver hepatocellular carcinoma, kidney renal papillary cell carcinoma, and pheochromocytoma and paraganglioma. Moreover, there were significant positive correlations between NAT10 expression and immune infiltrates, including B cells, CD8+ T cells, CD4+ T cells, neutrophils, macrophages, dendritic cells, endothelial cells, and fibroblasts in LIHC. NAT10 expression showed strong correlations with diverse immune marker gene sets in LIHC.

CONCLUSION: NAT10 expression affects the prognosis of pan-cancer patients and is significantly correlated with tumor immune infiltration. Furthermore, it represents a potential target for cancer therapy.

PMID:34094911 | PMC:PMC8170476 | DOI:10.3389/fonc.2021.630417

Adrenal tumors provide insight into the role of cortisol in NK cell activity

Fetched: June 5th, 2021, 5:00am GMT by Andrew E Greenstein

Endocr Relat Cancer. 2021 Jun 1:ERC-21-0048.R2. doi: 10.1530/ERC-21-0048. Online ahead of print.

ABSTRACT

PMID:34086600 | DOI:10.1530/ERC-21-0048

Virilising adrenocortical carcinoma

Fetched: June 5th, 2021, 5:00am GMT by Diogo Nunes Correia

BMJ Case Rep. 2021 Jun 2;14(6):e242895. doi: 10.1136/bcr-2021-242895.

ABSTRACT

PMID:34083198 | PMC:PMC8174502 | DOI:10.1136/bcr-2021-242895

The Immunotherapy Landscape in Adrenocortical Cancer

Fetched: June 3rd, 2021, 5:00am GMT by Guillaume J Pegna

Cancers (Basel). 2021 May 28;13(11):2660. doi: 10.3390/cancers13112660.

ABSTRACT

PMID:34071333 | PMC:PMC8199088 | DOI:10.3390/cancers13112660

Permalink for 'Differential Expression Profiles of Cell-to-Matrix-Related Molecules in Adrenal Cortical Tumors: Diagnostic and Prognostic Implications'

Differential Expression Profiles of Cell-to-Matrix-Related Molecules in Adrenal Cortical Tumors: Diagnostic and Prognostic Implications

Fetched: June 3rd, 2021, 5:00am GMT by Marco Volante

J Pers Med. 2021 May 6;11(5):378. doi: 10.3390/jpm11050378.

ABSTRACT

The molecular mechanisms of adrenocortical carcinoma development are incompletely defined. De-regulation of cellular-to-extracellular matrix interactions and angiogenesis appear among mechanisms associated to the malignant phenotype. Our aim was to investigate, employing PCR-based array profiling, 157 molecules involved in cell-to-matrix interactions and angiogenesis in a frozen series of 6 benign and 6 malignant adrenocortical neoplasms, to identify novel pathogenetic markers. In 14 genes, a significant dysregulation was detected in adrenocortical carcinomas as compared to adenomas, most of them being downregulated. Three exceptions-hyaluronan synthase 1 (HAS-1), laminin α3 and osteopontin genes-demonstrated an increased expression in adrenocortical carcinomas of 4.46, 4.23 and 20.32-fold, respectively, and were validated by immunohistochemistry on a series of paraffin-embedded tissues, including 20 adenomas and 73 carcinomas. Osteopontin protein, absent in all adenomas, was expressed in a carcinoma subset (25/73) (p = 0.0022). Laminin α3 and HAS-1 were mostly expressed in smooth muscle and endothelial cells of the vascular network of both benign and malignant adrenocortical tumors. HAS-1 was also detected in tumor cells, with a more intense pattern in carcinomas. In this group, strong expression was significantly associated with more favorable clinicopathological features. These data demonstrate that cell-to-matrix interactions are specifically altered in adrenocortical carcinoma and identify osteopontin and HAS-1 as novel potential diagnostic and prognostic biomarkers, respectively, in adrenal cortical tumors.

PMID:34066306 | PMC:PMC8148197 | DOI:10.3390/jpm11050378

The Sexually Dimorphic Adrenal Cortex: Implications for Adrenal Disease

Fetched: June 3rd, 2021, 5:00am GMT by Rodanthi Lyraki

Int J Mol Sci. 2021 May 5;22(9):4889. doi: 10.3390/ijms22094889.

ABSTRACT

PMID:34063067 | PMC:PMC8124132 | DOI:10.3390/ijms22094889

Permalink for 'Disparate Practice Patterns and Survival Outcomes: The Impact of Centralization of Cancer Care for Adrenocortical Carcinoma in the United States'

Disparate Practice Patterns and Survival Outcomes: The Impact of Centralization of Cancer Care for Adrenocortical Carcinoma in the United States

Fetched: May 26th, 2021, 5:00am GMT by Benjamin V Stone

J Urol. 2021 May 25:101097JU0000000000001871. doi: 10.1097/JU.0000000000001871. Online ahead of print.

ABSTRACT

PURPOSE: Adrenocortical carcinoma is a rare but aggressive malignancy. While centralization of care to referral centers improves outcomes across common urologic malignancies, there exists a paucity of data for low-incidence cancers. We sought to evaluate differences in practice patterns and overall survival in patients with adrenocortical carcinoma across types of treating facilities.

MATERIALS AND METHODS: We identified all patients diagnosed with ACC from 2004-2016 in the National Cancer Database. The Kaplan-Meier method was used to evaluate overall survival and multivariable Cox regression analysis was used to investigate independent predictors of OS. The chi-square test was used to analyze differences in practice patterns.

RESULTS: We identified 2,886 patients with adrenocortical carcinoma. Median overall survival was 21.8 months (95% CI 19.8-23.8). Academic centers had improved overall survival versus community centers on unadjusted Kaplan-Meier analysis (p <0.05) and had higher rates of adrenalectomy or radical en-bloc resection (p <0.001), performed more open surgery (p <0.001), administered more systemic therapy (p <0.001) and had lower rates of positive surgical margins (p=0.03). On multivariable analysis, controlling for treatment modality, academic centers were associated with significantly decreased risk of death (HR 0.779, 95% CI 0.631-0.963, p=0.021).

CONCLUSIONS: Treatment of adrenocortical carcinoma at an academic center is associated with improved overall survival compared to community programs. There are significant differences in practice patterns, including more aggressive surgical treatment at academic facilities, but the survival benefit persists on multivariable analysis controlling for treatment modality. Further studies are needed to identify the most important predictors of survival in this at-risk population.

PMID:34032493 | DOI:10.1097/JU.0000000000001871

Permalink for 'Homeobox A5 activates p53 pathway to inhibit proliferation and promote apoptosis of adrenocortical carcinoma cells by inducing Aldo-Keto reductase family 1 member B10 expression'

Homeobox A5 activates p53 pathway to inhibit proliferation and promote apoptosis of adrenocortical carcinoma cells by inducing Aldo-Keto reductase family 1 member B10 expression

Fetched: May 25th, 2021, 5:00am GMT by Danyan Chen

Bioengineered. 2021 Dec;12(1):1964-1975. doi: 10.1080/21655979.2021.1924545.

ABSTRACT

Aldo-Keto Reductase Family 1 Member B10 (AKR1B10) and Homeobox A5 (HOXA5) are both down-regulated in adrenocortical carcinoma (ACC), and HOXA5 is predicted to bind to the promoter of AKR1B10. We aimed to investigate whether HOXA5 could bind to AKR1B10 to regulate ACC cells proliferation and apoptosis. The expression of AKR1B10 and HOXA5 in ACC patients and the relationship of their expression between ACC prognosis were evaluated by searching database. Then, NCI-H295R cells were overexpressed to detect the alteration of cell proliferation, apoptosis and the expression of p53 and p21 proteins. The interaction between AKR1B10 and HOXA5 was validated by luciferase report and chromatin immunoprecipitation. Finally, NCI-H295R cells were silenced with HOXA5 in the presence of AKR1B10 overexpression, and then cell proliferation and apoptosis were also assessed. Results revealed that AKR1B10 and HOXA5 are down-regulated in ACC patients and the low expression of it is correlated with low percent of overall survival (OS) and disease free survival (DFS). Compared with Y1 cells, SW-13 and NCI-H295R cells exerted lower expression of AKR1B10 and HOXA5. AKR1B10 significantly inhibited cell viability, colony formation and expression of Ki67 and PCNA, but promoted apoptosis and expression of p53 and p21 in NCI-H295R cells. HOXA5 could interact with AKR1B10 and enhance AKR1B10 expression. Furthermore, HOXA5 knockdown obviously blocked the effect of AKR1B10 overexpression on NCI-H295R cells proliferation and apoptosis. In conclusion, HOXA5 could bind to AKR1B10 promotor to increase its expression, activate p53 signaling, thereby inhibiting proliferation and promoting apoptosis of ACC cells.

PMID:34027794 | DOI:10.1080/21655979.2021.1924545

Carcinoma of unknown primary origin with isolated adrenal metastasis: a report of two cases

Fetched: May 21st, 2021, 5:00am GMT by Mitsuhiro Kometani

Endocr J. 2021 May 18. doi: 10.1507/endocrj.EJ21-0141. Online ahead of print.

ABSTRACT

PMID:34011784 | DOI:10.1507/endocrj.EJ21-0141

Continuous and progressive 'wash-in' without 'wash-out' of contrast in adrenal mass: a useful feature of ganglioneuroma

Fetched: May 21st, 2021, 5:00am GMT by Neeti Agrawal

BMJ Case Rep. 2021 May 19;14(5):e241661. doi: 10.1136/bcr-2021-241661.

ABSTRACT

PMID:34011673 | PMC:PMC8137236 | DOI:10.1136/bcr-2021-241661

Metastasis of adrenocortical carcinoma to the heart: a case vignette

Fetched: May 20th, 2021, 5:00am GMT by Monika Kamilla Skrzypiec-Spring

Endokrynol Pol. 2021 May 19. doi: 10.5603/EP.a2021.0043. Online ahead of print.

ABSTRACT

A 32-year-old female patient was referred to the endocrine department from a gynecology and obstetrics department of a district hospital to which she was presented on the 4th day of childbed with severe headache, hypertension and bilateral leg edema and lumbar pain. Abdominal sonography taken there revealed a heterogeneous hypoechogenic mass in the the upper pole of the right kidney. This was confirmed by computed tomography. On admission the patient demonstrated elevated blood pressure, headache, hypertension, bilateral leg edema and severe abdominal and lumbar pain. Laboratory findings revealed leucocytosis 11.7 g% (normal range 4-10 K/µL), elevated levels of CRP 38.6 mg/l (normal range 0-3 mg/l), alanine aminotransferase 78 U/L (normal range 5-37 U/L), fibrinogen 800 mg% (normal range 200-450 mg%) and D-dimer 6950 ng/ml (normal range 70-490 ng/ml) and thrombocytopenia 91 K/µL (normal range 130-400 K/µL). Urine test revealed proteinuria and erythrocyturia in urine sediment. Hormonal study revealed elevated serum levels of cortisol 316.3 ng/ml at 8 a.m. (normal range 94-260 ng/ml) and 355.9 ng/ml at 12 p.m. (normal range 18-127 ng/ml) as well as decreased serum renin activity during recumbency 0.15 ng/ml/h (normal range 0,51-2,64 ng/ml/h) and 120 minutes of upright posture 0.39 ng/ml/h (normal range 0,98-4,18 ng/ml/h) and aldosterone levels during recumbency 21.3 pg/ml (normal range 29,4-161,5 pg/ml) and 120 minutes of upright posture 30.6 pg/ml (normal range 38,1-313,3 pg/ml). Trans-thoracic echocardiography indicated a large (3.8/2.8 cm) immobile right atrial mass attached to the atrial roof and the upper part of the interatrial septum as well as a mobile mass, attached to the atrial side of the anterior leaflet of the tricuspid valve, prolapsing through it. On the basis of these findings, the patient underwent urgent cardiosurgery and a large intra-atrial mass and tumor thrombi in inferior vena cava were removed. Pathologic examination demonstrated an adrenocortical carcinoma cells and a large area of necrosis within the tumor. Post-operatively, the patient did well and on 19th day was referred to urological ward for further treatment.

PMID:34010448 | DOI:10.5603/EP.a2021.0043

Permalink for 'Simulation-based interpretation of therapeutically monitored cabozantinib plasma concentration in advanced adrenocortical carcinoma with hemodialysis'

Simulation-based interpretation of therapeutically monitored cabozantinib plasma concentration in advanced adrenocortical carcinoma with hemodialysis

Fetched: May 19th, 2021, 5:00am GMT by Sebastian Zimmermann

Ther Drug Monit. 2021 May 12. doi: 10.1097/FTD.0000000000000905. Online ahead of print.

ABSTRACT

BACKGROUND: Adrenocortical carcinoma (ACC) is an orphan but aggressive malignancy with limited treatment options. Cabozantinib (CAB), a tyrosine kinase inhibitor (TKI), has emerged as a new potential treatment. However, no data are available on whether and how CAB can be administered to patients undergoing hemodialysis.

METHODS: An LC-MS/MS method was developed and validated according to the EMA and FDA guidelines for bioanalytical method validation. The samples were prepared using protein precipitation and online solid-phase extraction (SPE). The method was applied to clinical samples of an ACC patient receiving CAB treatment (80 mg daily). During the ten days of observation, the patient received periodic hemodialysis on seven days. Pharmacokinetic (PK) simulations were performed using Bayesian forecasting according to an existing population PK model for CAB.

RESULTS: Based on the PK simulation, a mean plasma trough concentration of 1375 ng/mL (90% prediction interval (PI) 601-2602 ng/mL) in the steady state at a daily dose of 80 mg was expected for CAB. However, an individual simulation involving the measured plasma levels of the patient resulted in a mean trough concentration of 348 ng/mL (90% PI 278-430 ng/mL). The model based on individual PK parameters estimated accessible plasma levels of 521, 625, and 834 ng/mL by dose adjustment to 100, 120, and 160 mg, respectively.

CONCLUSION: After establishing an LC-MS/MS method for therapeutic drug monitoring (TDM) of CAB, our analyses involving a single patient undergoing hemodialysis indicated that higher than expected doses of CAB were required to achieve reasonable plasma concentrations. Our study demonstrates the usefulness of TDM for the evaluation of 'new' drugs in patients with renal impairment.

PMID:34001696 | DOI:10.1097/FTD.0000000000000905

Cytotoxic Effect of Progesterone, Tamoxifen and Their Combination in Experimental Cell Models of Human Adrenocortical Cancer

Fetched: May 14th, 2021, 5:00am GMT by Elisa Rossini

Front Endocrinol (Lausanne). 2021 Apr 26;12:669426. doi: 10.3389/fendo.2021.669426. eCollection 2021.

ABSTRACT

PMID:33981288 | PMC:PMC8108132 | DOI:10.3389/fendo.2021.669426

Hypoglycemia in a Patient with Hypercortisolism and Adrenocortical Carcinoma: A Paradoxical Entity

Fetched: May 13th, 2021, 5:00am GMT by Sushmita Khadka

J Adolesc Young Adult Oncol. 2021 May 12. doi: 10.1089/jayao.2020.0229. Online ahead of print.

ABSTRACT

PMID:33978483 | DOI:10.1089/jayao.2020.0229

Case Report: Exceptional Response to Second Line Temozolomide Therapy in a Patient With Metastatic Adrenocortical Carcinoma

Fetched: May 11th, 2021, 5:00am GMT by Deborah Cosentini

Front Endocrinol (Lausanne). 2021 Apr 22;12:674039. doi: 10.3389/fendo.2021.674039. eCollection 2021.

ABSTRACT

BACKGROUND: In a recently published retrospective case series, Temozolomide was found active as second line approach in advanced ACC patients. The disease control rate obtained, however, was short-lived. We report here an ACC patient with extensive metastatic disease who obtained a remarkable long lasting response with this alkylating agent.

CASE PRESENTATION: a 22-year-old female patient with ACC presented at our Medical Oncology Department in poor general condition due the presence of extensive metastatic pulmonary involvement. The disease had progressed to etoposide, doxorubicin and cisplatin plus mitotane therapy. Second line temozolomide therapy was prescribed leading to a progressive improvement of patient general conditions. The disease restaging after 12 cycles revealed a complete response of lung lesions and the patient was free from progression for 14+ months.

CONCLUSION: Temozolomide therapy could be exceptionally efficacious in the management of ACC patients. The molecular mechanisms of sensitivity and resistance to this drug should be carefully studied, in order to select the patients destined to obtain a significant clinical benefit to the drug.

PMID:33967965 | PMC:PMC8101262 | DOI:10.3389/fendo.2021.674039

Advanced Adrenocortical Carcinoma: Current Perspectives on Medical Treatment

Fetched: May 9th, 2021, 5:00am GMT by Alexandra Novais Araújo

Horm Metab Res. 2021 May;53(5):285-292. doi: 10.1055/a-1453-0806. Epub 2021 May 7.

ABSTRACT

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy. For stage I and II tumors, surgery is a curative option, but even in these cases recurrence is frequent. Practical guidelines advocate a combination of mitotane with etoposide, doxorubicin, and cisplatin as first-line therapy for metastatic adrenocortical carcinoma. However, this scheme presents limited efficacy and high toxicity. The use of Immune Checkpoint Inhibitors (ICI) and multi-Tyrosine Kinase Inhibitors (mTKI) has modified the approach of multiple malignancies. The expectation of their applicability on advanced adrenocortical carcinoma is high but the role of these new therapies persists unclear. This article provides a short summary of last years' findings targeting outcomes, limitations, and adverse effects of these new therapeutic approaches. The results of recent trials and case series pointed pembrolizumab as the most promising drug among these new therapies. It is the most often used ICI and the one presenting the best results with less related adverse effects when in comparison to the standard treatment with mitotane. Hereafter, the identification of specific molecular biomarkers or immune profiles associated with ICI or mTKI good response will facilitate the selection of candidates for these therapies. So far, microsatellite instability and Lynch Syndrome related germline mutations are suggested as predictive biomarkers of good response. Contrarywise, cortisol secretion has been associated with more aggressive ACC tumors and potentially poor responses to immunotherapy.

PMID:33962475 | DOI:10.1055/a-1453-0806

Pediatric Cushing syndrome: An early sign of an underling cancer predisposition syndrome

Fetched: May 8th, 2021, 5:00am GMT by Bahareh M Schweiger

Am J Med Genet A. 2021 May 7. doi: 10.1002/ajmg.a.62255. Online ahead of print.

ABSTRACT

Beckwith-Wiedemann syndrome (BWS) is a genetic overgrowth and cancer predisposition syndrome that can be associated with a spectrum of clinical features including isolated lateralized overgrowth, macrosomia, macroglossia, organomegaly, omphalocele/umbilical hernia, and distinct facial features. Because of a range of clinical presentations and molecular defects involving Chromosome 11p15, many cases will fall within what is now being defined as the Beckwith-Wiedemann spectrum (BWSp). Cushing syndrome (CS) in infants is a rare neuroendocrinological disease associated with hypercortisolism that has rarely been reported in patients with BWS. Here, we describe the first case of a 5-month-old male with CS secondary to paternal uniparental disomy of Chromosome 11p without additional clinical signs or symptoms of BWS. This case continues to expand the phenotypic spectrum of BWSp.

PMID:33960620 | DOI:10.1002/ajmg.a.62255

Permalink for 'Functional Adrenocortical Carcinoma: A Rare Case With Thrombus Extension Into the Inferior Vena Cava and a Presentation of Cushing Syndrome'

Functional Adrenocortical Carcinoma: A Rare Case With Thrombus Extension Into the Inferior Vena Cava and a Presentation of Cushing Syndrome

Fetched: May 8th, 2021, 5:00am GMT by Thomas M Southall

Cureus. 2021 Apr 1;13(4):e14239. doi: 10.7759/cureus.14239.

ABSTRACT

Adrenocortical carcinoma (ACC) is a rare, highly malignant endocrine tumor, often associated with a poor prognosis. Most patients who develop ACC are either children of ages 1-6, or adults in their fourth to fifth decade of life. Individuals with a functional cortisol-secreting ACC frequently present with Cushing syndrome. We report a case of an 18-year-old male who was found to have a large ACC tumor, with thrombus extension into the inferior vena cava (IVC), after presenting with Cushing syndrome. ACC presents a challenging scenario for physicians as surgical resection remains the only form of curative therapy, however, despite such treatment many patients quickly develop metastases.

PMID:33959434 | PMC:PMC8093109 | DOI:10.7759/cureus.14239

Adrenal and Hepatic Venous Sampling in a Case of Aldosterone-Producing Adrenocortical Carcinoma with Hepatic Metastasis

Fetched: May 7th, 2021, 5:00am GMT by Toru Sugiyama

Case Rep Endocrinol. 2021 Apr 14;2021:5584198. doi: 10.1155/2021/5584198. eCollection 2021.

ABSTRACT

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and highly aggressive malignancy. ACCs often secrete adrenal steroid hormones including cortisol and androgens; however, aldosterone-producing ACC is very rare. Although adrenal production of aldosterone is assessed by adrenal venous sampling, the use of sampling from the relevant vein to assess aldosterone production from a tumor arising from ACC metastasis has not been previously reported. Case Presentation. We report the case of a 69-year-old Japanese man with aldosterone-producing ACC with hepatic metastasis. He presented with a history of treatment-resistant hypertension and hypokalemia. Endocrinological examination showed markedly increased plasma aldosterone concentration and suppressed plasma renin activity. Serum cortisol concentration was not suppressed by administration of dexamethasone 1 mg, and normal circadian variation of cortisol secretion was disrupted. Abdominal computed tomography showed a large tumor in the left adrenal gland and multiple tumors in the liver. Together, these results strongly suggested ACC with multiple liver metastases causing primary aldosteronism and subclinical Cushing syndrome. Adrenal and hepatic venous sampling showed markedly increased aldosterone concentration in the left adrenal vein but no increase in the hepatic vein, despite a pathological diagnosis of ACC with hepatic metastasis, with immunohistochemical investigation showing both primary and secondary tumors to have synthetic capability for aldosterone. The patient received mitotane but declined combination chemotherapy and died 2 months later.

CONCLUSION: This is the first report of adrenal and hepatic venous sampling in a case of aldosterone-producing ACC with hepatic metastasis. The case suggests that hepatic venous sampling is unable to detect aldosterone production from liver metastases arising from ACC.

PMID:33953990 | PMC:PMC8062207 | DOI:10.1155/2021/5584198

Permalink for 'Bioinformatic analyses and experimental validation of the role of m6A RNA methylation regulators in progression and prognosis of adrenocortical carcinoma'

Bioinformatic analyses and experimental validation of the role of m6A RNA methylation regulators in progression and prognosis of adrenocortical carcinoma

Fetched: May 7th, 2021, 5:00am GMT by Fangshi Xu

Aging (Albany NY). 2021 Apr 21;13(8):11919-11941. doi: 10.18632/aging.202896. Epub 2021 Apr 21.

ABSTRACT

M6A-related genes have been proven to play an important role in many cancers. However, the role of that in adrenocortical carcinoma (ACC) has not been fully elucidated. In the present study, 77 ACC samples from TCGA database were divided into localized (n = 46) and metastatic (n = 31) groups. Three differential expression genes (DEGs) and five prognostic m6A genes were screened out. M6A-related risk signature (RBM15 and HNRNPC) was constructed by the Lasso regression analysis. In TCGA cohort (training cohort), the risk signature was identified as an ACC-independent prognostic factor and can distinguish the prognostic difference of ACC patients with clinical stage I-II, T3-4 and N0 stages. A nomogram combining T stage and m6A risk score was constructed to predict the overall survival rate (OSR) of individual at 1,2,3 year. Meanwhile, its prognostic value was also confirmed in the validation cohort (GSE33371 dataset). The potential associations between m6A risk level and immune checkpoint inhibitors (ICIs) therapy were also investigated via the TISIDB online tool. High m6A risk not only can suppress immunotherapy-related biological processes, but also repress the expressions of immune-checkpoint markers. Moreover, five pairs of clinical specimens were collected to confirm the overexpression of HNRNPC and non-ectopic expression of RBM15 in tumor tissues. HNRNPC was proven to promote the proliferation, migration and invasion of H295R and SW13 cells through MTT and Transwell assays. In conclusion, the m6A-related risk signature was beneficial for prognostic analysis and can affect immune microenvironment in ACC. HNRNPC played a pro-cancer role in ACC progression.

PMID:33952721 | PMC:PMC8109058 | DOI:10.18632/aging.202896

Adrenocortical Carcinoma: A Case of Missed Diagnosis

Fetched: May 6th, 2021, 5:00am GMT by Yusef Hazimeh

Cureus. 2021 Apr 1;13(4):e14235. doi: 10.7759/cureus.14235.

ABSTRACT

PMID:33948420 | PMC:PMC8087872 | DOI:10.7759/cureus.14235

Permalink for 'Pancancer Analysis of Neurovascular-Related NRP Family Genes as Potential Prognostic Biomarkers of Bladder Urothelial Carcinoma'

Pancancer Analysis of Neurovascular-Related NRP Family Genes as Potential Prognostic Biomarkers of Bladder Urothelial Carcinoma

Fetched: May 4th, 2021, 5:00am GMT by Chao Deng

Biomed Res Int. 2021 Apr 15;2021:5546612. doi: 10.1155/2021/5546612. eCollection 2021.

ABSTRACT

BACKGROUND: Neurovascular-related genes have been implicated in the development of cancer. Studies have shown that a high expression of neuropilins (NRPs) promotes tumourigenesis and tumour malignancy.

METHOD: A multidimensional bioinformatics analysis was performed to examine the relationship between NRP genes and prognostic and pathological features, tumour mutational burden (TMB), microsatellite instability (MSI), and immunological features based on public databases and find the potential prognostic value of NRPs in pancancer.

RESULTS: Survival analysis revealed that a low NRP1 expression in adrenocortical carcinoma (ACC), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), low-grade glioma (LGG), and stomach adenocarcinoma (STAD) was associated with poor prognosis. A high NRP2 expression in bladder urothelial carcinoma (BLCA), kidney renal papillary cell carcinoma (KIRP), and mesothelioma (MESO) was associated with poor prognosis. Moreover, NRP1 and NRP2 were associated with TMB and MSI. Subsequent analyses showed that NRP1 and NRP2 were correlated with immune infiltration and immune checkpoints. Genome-wide association analysis revealed that the NRP1 expression was strongly associated with kidney renal clear cell carcinoma (KIRC), whereas the NRP2 expression was closely associated with BLCA. Ultimately, NRP2 was found to be involved in the development of BLCA.

CONCLUSIONS: Neurovascular-related NRP family genes are significantly correlated with cancer prognosis, TME, and immune infiltration, particularly in BLCA.

PMID:33937395 | PMC:PMC8062179 | DOI:10.1155/2021/5546612

Squamous Cell Carcinoma of the Lung in McCune-Albright Syndrome

Fetched: May 4th, 2021, 5:00am GMT by Vinai Y Reddy

Cureus. 2021 Mar 28;13(3):e14159. doi: 10.7759/cureus.14159.

ABSTRACT

McCune Albright Syndrome (MAS) is caused by a mutation in the GNAS gene that results in multiple endocrinopathies such as Cushing syndrome, acromegaly, hyperthyroidism, and precocious puberty. Despite the presence of pleiotropy coupled with a GNAS gene mutation, malignancy is a rare occurrence in MAS. There is minimal literature showcasing squamous cell carcinoma (SCC) of the lung in patients with MAS. Here, we report a case of altered mental status and hypercalcemia in a 72-year-old female with a past medical history of fibrous dysplasia. On examination there was an expansive lesion of the left hemipelvis that had been present since birth; it was determined to be a characteristic of polyostotic fibrous dysplasia seen in MAS. Lab results revealed an elevated parathyroid hormone-related protein (PTHrP) and a chest X-ray (CXR) displayed masses in the right upper lobe. Computed tomography (CT)-guided lung biopsy confirmed the masses to be SCC of the lung. This case primarily highlights the importance of investigating other malignancies found in patients with MAS. Current literature shows that the GNAS mutation is an oncogenic driver in many tumor types such as pancreatic adenocarcinoma, adrenocortical carcinoma, and thyroid carcinoma; however, current data are limited on the role of GNAS mutations in SCC of the lung. In addition, it is important to investigate malignant causes of hypercalcemia in patients with MAS. The clinical features and treatments of MAS can lead to hypercalcemia and hypophosphatemia and thus mask a malignancy. Clinicians must be wary of a masked malignancy, as it could delay treatment and negatively impact overall outcomes for patients with MAS.

PMID:33936872 | PMC:PMC8078556 | DOI:10.7759/cureus.14159

Tumor Microenvironment in Adrenocortical Carcinoma: Barrier to Immunotherapy Success?

Fetched: May 1st, 2021, 5:00am GMT by Natalia Georgantzoglou

Cancers (Basel). 2021 Apr 9;13(8):1798. doi: 10.3390/cancers13081798.

ABSTRACT

Adrenocortical carcinoma is a rare malignancy with aggressive behavior, with up to 40% of patients presenting with metastases at the time of diagnosis. Both conventional chemotherapeutic regimens and novel immunotherapeutic agents, many of which are currently being tested in ongoing clinical trials, have yielded modest results so far, bringing the need for a deeper understanding of adrenal cancer behavior to the forefront. In the recent years, the tumor microenvironment has emerged as a major determinant of cancer response to immunotherapy and an increasing number of studies on other solid tumors have focused on manipulating the microenvironment in the favor of the host and discovering new potential target molecules. In the present review we aim to explore the characteristics of adrenocortical cancer's microenvironment, highlighting the mechanisms of immune evasion responsible for the modest immunotherapeutic results, and identify novel potential strategies.

PMID:33918733 | PMC:PMC8069982 | DOI:10.3390/cancers13081798

Epithelial and Mesenchymal Markers in Adrenocortical Tissues: How Mesenchymal Are Adrenocortical Tissues?

Fetched: May 1st, 2021, 5:00am GMT by Iuliu Sbiera

Cancers (Basel). 2021 Apr 6;13(7):1736. doi: 10.3390/cancers13071736.

ABSTRACT

A clinically relevant proportion of adrenocortical carcinoma (ACC) cases shows a tendency to metastatic spread. The objective was to determine whether the epithelial to mesenchymal transition (EMT), a mechanism associated with metastasizing in several epithelial cancers, might play a crucial role in ACC. 138 ACC, 29 adrenocortical adenomas (ACA), three normal adrenal glands (NAG), and control tissue samples were assessed for the expression of epithelial (E-cadherin and EpCAM) and mesenchymal (N-cadherin, SLUG and SNAIL) markers by immunohistochemistry. Using real-time RT-PCR we quantified the alternative isoform splicing of FGFR 2 and 3, another known indicator of EMT. We also assessed the impact of these markers on clinical outcome. Results show that both normal and neoplastic adrenocortical tissues lacked expression of epithelial markers but strongly expressed mesenchymal markers N-cadherin and SLUG. FGFR isoform splicing confirmed higher similarity of adrenocortical tissues to mesenchymal compared to epithelial tissues. In ACC, higher SLUG expression was associated with clinical markers indicating aggressiveness, while N-cadherin expression inversely associated with these markers. In conclusion, we could not find any indication of EMT as all adrenocortical tissues lacked expression of epithelial markers and exhibited closer similarity to mesenchymal tissues. However, while N-cadherin might play a positive role in tissue structure upkeep, SLUG seems to be associated with a more aggressive phenotype.

PMID:33917436 | PMC:PMC8038668 | DOI:10.3390/cancers13071736

What Is the Optimal Duration of Adjuvant Mitotane Therapy in Adrenocortical Carcinoma? An Unanswered Question

Fetched: May 1st, 2021, 5:00am GMT by Vittoria Basile

J Pers Med. 2021 Apr 4;11(4):269. doi: 10.3390/jpm11040269.

ABSTRACT

A relevant issue on the treatment of adrenocortical carcinoma (ACC) concerns the optimal duration of adjuvant mitotane treatment. We tried to address this question, assessing whether a correlation exists between the duration of adjuvant mitotane treatment and recurrence-free survival (RFS) of patients with ACC. We conducted a multicenter retrospective analysis on 154 ACC patients treated for ≥12 months with adjuvant mitotane after radical surgery and who were free of disease at the mitotane stop. During a median follow-up of 38 months, 19 patients (12.3%) experienced recurrence. We calculated the RFS after mitotane (RFSAM), from the landmark time-point of mitotane discontinuation, to overcome immortal time bias. We found a wide variability in the duration of adjuvant mitotane treatment among different centers and also among patients cared for at the same center, reflecting heterogeneous practice. We did not find any survival advantage in patients treated for longer than 24 months. Moreover, the relationship between treatment duration and the frequency of ACC recurrence was not linear after stratifying our patients in tertiles of length of adjuvant treatment. In conclusion, the present findings do not support the concept that extending adjuvant mitotane treatment over two years is beneficial for ACC patients with low to moderate risk of recurrence.

PMID:33916613 | PMC:PMC8066814 | DOI:10.3390/jpm11040269

Permalink for 'Curcumin induces apoptosis and inhibits the growth of adrenocortical carcinoma: Identification of potential candidate genes and pathways by transcriptome analysis'

Curcumin induces apoptosis and inhibits the growth of adrenocortical carcinoma: Identification of potential candidate genes and pathways by transcriptome analysis

Fetched: April 29th, 2021, 5:00am GMT by Xuemei Huang

Oncol Lett. 2021 Jun;21(6):476. doi: 10.3892/ol.2021.12737. Epub 2021 Apr 15.

ABSTRACT

Adrenocortical carcinoma (ACC) is an endocrine tumour with high malignancy, high invasiveness and poor prognosis. Curcumin, a major component in turmeric, has been reported to have good efficacy and biological safety in treating cancer. However, the role and mechanism of curcumin in ACC have not yet been fully investigated and were thus the focus of this study. In vitro, ACC SW-13 and NCI-H295R cells were treated with curcumin and their viability, migration and invasion were assessed by CCK-8 and Transwell assays. Apoptosis was detected via flow cytometry and western blotting. High-throughput sequencing and comprehensive bioinformatics analyses were performed to elucidate the molecular processes underlying curcumin activity. In vivo, SW-13 cells were injected into nude mice, and the tumour volumes and weights were observed after 2 weeks of curcumin treatment. Organelle changes were observed by electron microscopy, and potential candidate genes and pathways were analysed by RT-qPCR and western blotting. The role of the CHOP target gene in curcumin-induced ACC cell apoptosis was verified via lentiviral transfection experiments. Curcumin inhibited the viability, migration and invasion, and induced the apoptosis of ACC cells. Transcriptome sequencing analysis showed that curcumin treatment markedly changed the gene expression levels. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses showed that the MAPK and endoplasmic reticulum (ER) stress pathways were the predominant pathways associated with curcumin-induced apoptosis of ACC cells. Subsequent in vivo and in vitro results demonstrated that the JNK, p38 MAPK and ER stress pathways were activated in curcumin-treated ACC cells, and that C/EBP homologous protein induction was responsible for curcumin-induced apoptosis of ACC cells. In summary, curcumin induced ACC cell apoptosis and inhibited tumour growth by activating the JNK, p38 MAPK and ER stress pathways. Thus, curcumin may be a potential therapeutic drug for ACC.

PMID:33907586 | PMC:PMC8063251 | DOI:10.3892/ol.2021.12737

Permalink for 'In vitro cytotoxic effect of a chitin-like polysaccharide produced by Mortierella alpina on adrenocortical carcinoma cells H295R, and its use as mitotane adjuvant'

In vitro cytotoxic effect of a chitin-like polysaccharide produced by Mortierella alpina on adrenocortical carcinoma cells H295R, and its use as mitotane adjuvant

Fetched: April 28th, 2021, 5:00am GMT by Luis Daniel Goyzueta Mamani

In Vitro Cell Dev Biol Anim. 2021 Apr;57(4):395-403. doi: 10.1007/s11626-021-00560-y. Epub 2021 Apr 26.

ABSTRACT

This study presents an in vitro evaluation of the antitumor potential of a chitin-like exopolysaccharide (EPS, produced by Mortierella alpina) on Adrenocortical carcinoma cells (ACC) compared to mitotane, a commercial drug commonly used in ACC treatment, and known for its side effects. Techniques of cellular viability determination such as MTT and fluorescence were used to measure the cytotoxic effects of the EPS and mitotane in tumoral cells (H295R) and non-tumoral cells (VERO), observing high cytotoxicity of mitotane and a 10% superior pro-apoptotic effect of the EPS compared to mitotane (p < 0.05). The cytotoxic effect of the EPS was similar to the effect of 50 μM mitotane on tumoral cells (p < 0.05). A decrement of the lysosomal volume was also noted in tumoral cells treated with the EPS. To enhance the antitumor effect, a combination of mitotane at a lower dosage and the EPS (as adjuvant) was also tested, showing a slight improvement of the cytotoxicity effect on tumoral cells. Therefore, the results indicate a cytotoxic effect of the EPS produced by Mortierella alpina on adrenocortical carcinoma, and a possible application in biomedical formulations or additional treatments.

PMID:33904018 | DOI:10.1007/s11626-021-00560-y

Striae and an Adrenal Mass

Fetched: April 28th, 2021, 5:00am GMT by Jennifer H Yo

N Engl J Med. 2021 Apr 22;384(16):e57. doi: 10.1056/NEJMicm2024730.

NO ABSTRACT

PMID:33882208 | DOI:10.1056/NEJMicm2024730

Emerging drugs for the treatment of Adrenocortical Carcinoma

Fetched: April 27th, 2021, 5:00am GMT by Vineeth Sukrithan

Expert Opin Emerg Drugs. 2021 Jun;26(2):165-178. doi: 10.1080/14728214.2021.1920922. Epub 2021 May 3.

ABSTRACT

Introduction: Adrenocortical cancer (ACC) is a rare and aggressive disease with a median survival of 14-17 months and 5-year survival of around 20% for advanced disease. Emerging evidence of sub-groups of ACC with specific molecular drivers indicate ACC may be amenable to inhibition of receptor tyrosine kinases involved in growth and angiogenic signaling. A significant subset of patients may also be responsive to immune strategies.Areas covered: This review outlines approaches of targeting upregulated growth pathways including Insulin-like Growth Factor, Vascular Endothelial Growth Factor, Fibroblast Growth Factor and Epidermal Growth Factor Receptor in ACC. Data of immune checkpoint blockade with nivolumab, ipilimumab, pembrolizumab and avelumab is explored in detail. Genomic studies indicate that up to 40% of ACC are driven by dysregulated WNT and glucocorticoid signaling, special focus is placed on emerging drugs in these pathways.Expert opinion: Progress in the treatment of ACC has faced challenges stemming from the rarity of the disease. Given recent advances in the understanding of the molecular pathogenesis of ACC, a window of opportunity has now opened to make significant progress in developing therapeutic options that target key pathways such as excessive glucocorticoid signaling, WNT signaling, cell cycle and immune checkpoints.

PMID:33896321 | DOI:10.1080/14728214.2021.1920922

Permalink for 'Combination immunotherapy with ipilimumab and nivolumab in patients with advanced adrenocortical carcinoma: a subgroup analysis of CA209-538'

Combination immunotherapy with ipilimumab and nivolumab in patients with advanced adrenocortical carcinoma: a subgroup analysis of CA209-538

Fetched: April 24th, 2021, 5:00am GMT by Oliver Klein

Oncoimmunology. 2021 Apr 12;10(1):1908771. doi: 10.1080/2162402X.2021.1908771.

ABSTRACT

Background: Adrenocortical carcinoma is a rare malignancy, with poor prognosis and limited treatment options for patients with advanced disease. Chemotherapy is the current standard first-line treatment, providing only a modest survival benefit. There is only limited treatment experience with immunotherapy using single-agent anti-PD-1/PD-L1 therapy. To date no clinical trials have been reported using combination immunotherapy with anti-CTLA-4 and anti-PD-1 blockade in this patient population. Methods: CA209-538 is a prospective multicentre clinical trial in patients with advanced rare cancers. Participants received the anti-PD-1 antibody nivolumab (3 mg/kg IV) and the anti-CTLA-4 antibody ipilimumab (1 mg/kg IV) every three weeks for four doses, followed by nivolumab (3 mg/kg IV) every two weeks and continued for up to 96 weeks, until disease progression or unacceptable toxicity. Response was assessed every 12 weeks by RECIST version 1.1. Primary endpoint was clinical benefit rate (complete response, partial response, stable disease at 12 weeks). Results: Six patients with adrenocortical carcinoma were enrolled and received treatment. Two patients (33%) have an ongoing partial response (10 and 25 months +) and two patients (33%) stable disease leading to a disease control rate of 66%. Both responders had tumors with a microsatellite instable phenotype. One patient rapidly progressed shortly after enrollment into the trial and did not undergo restaging. Immunotherapy-related toxicity was reported in all patients, with four patients (67%) experiencing grade 3/4 hepatitis leading to discontinuation of treatment. Conclusions: This is the first treatment experience using ipilimumab and nivolumab combination immunotherapy in patients with advanced adrenocortical carcinoma. Durable responses have been observed in a subset of patients suggesting that this treatment regimen should be further investigated in this patient population.

PMID:33889439 | PMC:PMC8043165 | DOI:10.1080/2162402X.2021.1908771

Vasoactive intestinal peptide producing pheochromocytoma and intracardiac thrombosis

Fetched: April 24th, 2021, 5:00am GMT by Melody Hermel

Rare Tumors. 2021 Apr 9;13:20363613211007792. doi: 10.1177/20363613211007792. eCollection 2021.

ABSTRACT

A case of pheochromocytoma producing vasoactive intestinal peptide (VIP) and left ventricular thrombus in the absence of cardiomyopathy or wall motion abnormalities on echocardiogram is presented along with a review of the relevant literature. A 30-year-old female of Afghani descent with past medical history of panic attacks presented with fever, cough, sore throat, vomiting, and was found to have an 11 cm adrenal mass consistent with primary adrenocortical adenoma versus carcinoma. Her tumor elicited catechols and vasoactive intestinal peptide. Her hospitalization was complicated by left ventricular thrombosis leading to an embolic injury to her right kidney, respiratory failure, need for transient dialysis and urinary tract infections. She developed a profuse secretory diarrhea and decision was made to treat with empiric octreotide infusion and imodium with improvement in symptoms. She underwent coil and particle embolization followed by resection. Followup PET gallium scan showed no evidence of residual disease or metastasis. VIP producing pheochromocytoma associated with intracardiac thrombosis is rare. Outcomes depend on prompt diagnosis of the pheochromocytoma and multidisciplinary approach to management.

PMID:33889374 | PMC:PMC8040591 | DOI:10.1177/20363613211007792

Predicting clinical outcomes using cancer progression associated signatures

Fetched: April 24th, 2021, 5:00am GMT by Jared Mamrot

Oncotarget. 2021 Apr 13;12(8):845-858. doi: 10.18632/oncotarget.27934. eCollection 2021 Apr 13.

ABSTRACT

Somatic mutation signatures are an informative facet of cancer aetiology, however they are rarely useful for predicting patient outcome. The aim of this study is to evaluate the utility of a panel of 142 mutation-signature-associated metrics (P142) for predicting cancer progression in patients from a 'TCGA PanCancer Atlas' cohort. The P142 metrics are comprised of AID/APOBEC and ADAR deaminase associated SNVs analyzed for codon context, strand bias, and transitions/transversions. TCGA tumor-normal mutation data was obtained for 10,437 patients, representing 31 of the most prevalent forms of cancer. Stratified random sampling was used to split patients into training, tuning and validation cohorts for each cancer type. Cancer specific machine learning (XGBoost) models were built using the output from the P142 panel to predict patient Progression Free Survival (PFS) status as either "High PFS" or "Low PFS". Predictive performance of each model was evaluated using the validation cohort. Models accurately predicted PFS status for several cancer types, including adrenocortical carcinoma, glioma, mesothelioma, and sarcoma. In conclusion, the P142 panel of metrics successfully predicted cancer progression status in patients with some, but not all cancer types analyzed. These results pave the way for future studies on cancer progression associated signatures.

PMID:33889305 | PMC:PMC8057277 | DOI:10.18632/oncotarget.27934

Non-functioning adrenocortical carcinoma

Fetched: April 24th, 2021, 5:00am GMT by Bui-Van Lenh

Radiol Case Rep. 2021 Apr 3;16(6):1329-1334. doi: 10.1016/j.radcr.2021.03.006. eCollection 2021 Jun.

ABSTRACT

Adrenocortical carcinoma (ACC) is a rare malignancy that arises from the adrenal cortex and can be classified as either non-functioning or functioning. A patient with non-functioning ACC may present no specific symptoms. Imaging analysis can provide some information to a clinician who suspects ACC, such as tumor size, density, washout, necrosis, hemorrhage, and calcification. Histopathology is used to confirm and determine the origin of the malignancy and can provide relevant prognostic information. Microscopic findings can be used to obtain information such as the Weiss score, resection surface features, Ki-67 proliferative index, and the degree of capsular and vascular invasion. Surgery can be curative for localized tumors, and adjuvant therapy using mitotane and cytotoxic chemotherapy is often employed for advanced-stage tumors. We describe a case report of a 32-year-old man with a non-functioning ACC that highlights the importance of radiological and pathological features in the diagnosis of ACC and their use as prognostic factors.

PMID:33889224 | PMC:PMC8049877 | DOI:10.1016/j.radcr.2021.03.006

Complete Radiological Response of Recurrent Metastatic Adrenocortical Carcinoma to Pembrolizumab and Mitotane

Fetched: April 24th, 2021, 5:00am GMT by Walid Alam

Clin Med Insights Oncol. 2021 Apr 8;15:11795549211007682. doi: 10.1177/11795549211007682. eCollection 2021.

ABSTRACT

Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis. Treatment options for ACC are limited, with resection the main intervention. Most cases present in late metastatic cases, and data regarding effective therapies is limited. We report a case of ACC in a 40-year-old woman with history of ACC postadrenalectomy, who presented with recurrent metastatic ACC in the left perinephric space. She was started on pembrolizumab which was added to her mitotane maintenance therapy. Complete radiological response was achieved after 4 cycles of pembrolizumab. As far as we know, this is the first case to achieve complete radiological response with mitotane and pembrolizumab in recurrent metastatic ACC, with negative prognostic markers and no prior radiotherapy. As our findings are in the setting of one clinical case, we suggest the need to perform a trial to assess the benefit of combining mitotane and pembrolizumab in treating metastatic ACC.

PMID:33889043 | PMC:PMC8040600 | DOI:10.1177/11795549211007682

Permalink for 'How close are we to personalized mitotane dosing in the treatment of adrenocortical carcinoma? State of the art and future perspectives'

How close are we to personalized mitotane dosing in the treatment of adrenocortical carcinoma? State of the art and future perspectives

Fetched: April 23rd, 2021, 5:00am GMT by Rebecca V Steenaard

Expert Opin Drug Metab Toxicol. 2021 Jun;17(6):677-683. doi: 10.1080/17425255.2021.1921146. Epub 2021 May 4.

ABSTRACT

INTRODUCTION: Mitotane is the only drug registered specifically for adrenocortical carcinoma. Finding the optimal dose for a patient is difficult due to large differences in bioavailability, toxicity and effect. We therefore look to improve personalized dosing of mitotane.

AREAS COVERED: We searched PubMed for studies related to mitotane dosing, pharmacokinetics, pharmacogenetics and combination therapy. Comparison of different dosing strategies have not resulted in an optimal advice. Several computerized pharmacokinetic models have been proposed to predict plasma levels. The current pharmacokinetic models do not explain the full variance in plasma levels. Pharmacogenetics have been proposed to find the unexplained variance. Studies on combination therapy have not yet led to a potential dose adjustment for mitotane.

EXPERT OPINION: Computerized pharmacokinetics models are promising tools to predict plasma levels, further validation is needed. Pharmacogenetics are introduced in these models, but more research is required before clinical application. We believe that in the near future, personalized mitotane dosage will be aided by a validated web-based pharmacokinetic model with good predictive ability based primarily on clinical characteristics, adjustable for actual plasma levels and dosage.

PMID:33886381 | DOI:10.1080/17425255.2021.1921146

Permalink for 'American Association of Clinical Endocrinology Disease State Clinical Review on the Evaluation and Management of Adrenocortical Carcinoma in an Adult: a Practical Approach'

American Association of Clinical Endocrinology Disease State Clinical Review on the Evaluation and Management of Adrenocortical Carcinoma in an Adult: a Practical Approach

Fetched: April 21st, 2021, 5:01am GMT by Katja Kiseljak-Vassiliades

Endocr Pract. 2020 Nov;26(11):1366-1383. doi: 10.4158/DSCR-2020-0567. Epub 2020 Dec 14.

ABSTRACT

OBJECTIVE: The aim of this Disease State Clinical Review is to provide a practical approach to patients with newly diagnosed adrenocortical carcinoma, as well as to follow-up and management of patients with persistent or recurrent disease.

METHODS: This is a case-based clinical review. The provided recommendations are based on evidence available from randomized prospective clinical studies, cohort studies, cross-sectional and case-based studies, and expert opinions.

RESULTS: Adrenocortical carcinoma is a rare malignancy, often with poor outcomes. For any patient with an adrenal mass suspicious for adrenocortical carcinoma, the approach should include prompt evaluation with detailed history and physical exam, imaging, and biochemical adrenal hormone assessment. In addition to adrenal-focused imaging, patients should be evaluated with chest-abdomen-pelvis cross-sectional imaging to define the initial therapy plan. Patients with potentially resectable disease limited to the adrenal gland should undergo en bloc open surgery by an expert surgeon. For patients presenting with advanced or recurrent disease, a multidisciplinary approach considering curative repeat surgery, local control with surgery, radiation therapy or radiofrequency ablation, or systemic therapy with mitotane and/or cytotoxic chemotherapy is recommended.

CONCLUSION: As most health care providers will rarely encounter a patient with adrenocortical carcinoma, we recommend that patients with suspected adrenocortical carcinoma be evaluated by an expert multidisciplinary team which includes clinicians with expertise in adrenal tumors, including endocrinologists, oncologists, surgeons, radiation oncologists, pathologists, geneticists, and radiologists. We recommend that patients in remote locations be followed by the local health care provider in collaboration with a multidisciplinary team at an expert adrenal tumor program.

ABBREVIATIONS: ACC = adrenocortical carcinoma; ACTH = adrenocorticotropic hormone; BRACC = borderline resectable adrenocortical carcinoma; CT = computed tomography; DHEAS = dehydroepiandrosterone sulfate; EDP = etoposide, doxorubicin, cisplatin; FDG = ¹⁸F-fluorodeoxyglucose; FNA = fine-needle aspiration; HU = Hounsfield units; IVC = inferior vena cava; LFS = Li-Fraumeni syndrome; MEN1 = multiple endocrine neoplasia type 1; MRI = magnetic resonance imaging; OAC = oncocytic adrenocortical carcinoma; PC = palliative care; PET = positron emission tomography.

PMID:33875173 | PMC:PMC8058447 | DOI:10.4158/DSCR-2020-0567

A Novel Diagnostic Model for Primary Adrenal Lymphoma

Fetched: April 20th, 2021, 5:00am GMT by Kai Yu

Front Endocrinol (Lausanne). 2021 Apr 2;12:636658. doi: 10.3389/fendo.2021.636658. eCollection 2021.

ABSTRACT

OBJECTIVE: Primary adrenal lymphoma (PAL) is easily misdiagnosed as other adrenal masses, such as adrenocortical carcinoma and pheochromocytoma, but patients with PAL benefit little from surgery. The diagnostic method for PAL thus far is limited to adrenal biopsy. In our study, we aimed to develop a quick and efficient diagnostic method for PAL.

METHODS AND RESULTS: At the same institution, 505 patients (between 2009 and 2019) and 171 patients (between 2019 and 2020) were separately included in the primary and validation studies. Univariate and multivariate analyses were conducted to evaluate clinical manifestations, laboratory findings, and radiological characteristics. Four determinants (age, bilateral masses, high-density lipoprotein cholesterol, and lactate dehydrogenase) were selected and further incorporated into a regression model to screen PAL. Accordingly, the nomogram was developed for clinical practice. In the primary study, the nomogram showed good discrimination, with an area under the receiver operating characteristic (ROC) curve (AUC) of 95.4% (95% CI, 90.6%-100.0%). Further validation study verified the efficacy of the nomogram, with an AUC of 99.0% (95% CI, 96.9%-100.00%) and 100.0% in all patients and patients with bilateral masses, respectively, and a sensitivity/specificity/positive predictive value (PPV)/negative predictive value (NPV) of 66.67%/99.40%/66.67%/99.40%, 66.67%/100%/100%/92.86%, 50%/99.20%/50%/99.20%, and 100%/100%/100%/100%, in all patients, patients with bilateral adrenal masses, patients with nonfunctional adrenal masses, and patients with positive catecholamine results, respectively. The validation study also revealed a diagnostic specificity of 99.35% and 100% for patients with a unilateral adrenal mass and functional PCC, respectively.

CONCLUSIONS: The presented nomogram is the first user-friendly diagnostic model for PAL that simplifies the complex diagnostic process into personalized numeric estimates. We deem that patients who score below 50 are less likely to have PAL. We suggest that clinicians should arrange adrenal biopsy and surgery for patients with nonfunctional tumors and overt catecholamine-secreting tumors, respectively, who receive a score of 50 points or higher to confirm the diagnosis as soon as possible.

PMID:33868171 | PMC:PMC8050348 | DOI:10.3389/fendo.2021.636658

Permalink for 'Stage Presentation, Care Patterns, Treatment Outcomes, and Impact of Radiotherapy on Overall Survival for Adrenocortical Carcinoma'

Stage Presentation, Care Patterns, Treatment Outcomes, and Impact of Radiotherapy on Overall Survival for Adrenocortical Carcinoma

Fetched: April 17th, 2021, 5:00am GMT by Justin J Thomas

Clin Genitourin Cancer. 2021 Mar 19:S1558-7673(21)00072-0. doi: 10.1016/j.clgc.2021.03.009. Online ahead of print.

ABSTRACT

INTRODUCTION: Adrenocortical carcinoma (ACC) is a rare cancer with few well-powered studies regarding epidemiology or outcomes and even fewer studies to guide an evidence-based management approach. The effect of radiation therapy (RT) is particularly understudied and remains unclear, outside of general oncologic principles. We sought to describe current care patterns in the management of ACC and how these practices affect survival outcomes using the Surveillance, Epidemiology, and End Results (SEER) database.

METHODS: Patients with ACC who could be staged by the American Joint Committee on Cancer (AJCC) system diagnosed between 1988 and 2015 were included. A classification and regression tree analysis identified subgroups of patients who may have benefitted from RT. Multivariable Cox regression analysis was used to compare overall survival (OS). Propensity score adjustment was used to compare OS for a subset of node-negative, nonmetastatic patients who received adjuvant RT following radical surgery.

RESULTS: Among 865 eligible patients included in the analysis, only 10.5% received RT. In stage III node-negative patients, adjuvant RT following radical surgery was associated with a significantly improved OS compared with surgery alone.

CONCLUSION: Medically fit persons with stage III, node-negative ACC should receive adjuvant RT after surgical resection.

PMID:33858789 | DOI:10.1016/j.clgc.2021.03.009

Estrogen-secreting adrenocortical tumor in a postmenopausal woman: a challenging diagnosis

Fetched: April 13th, 2021, 5:00am GMT by L M Mermejo

Endocrinol Diabetes Metab Case Rep. 2021 Mar 15;2021:20-0214. doi: 10.1530/EDM-20-0214. Online ahead of print.

ABSTRACT

SUMMARY: Adrenocortical carcinoma (ACC) is a malignant disorder with rapid evolution and severe prognosis in adults and most produce cortisol and androgen. Estrogen-secreting adrenocortical carcinomas are extremely rare, especially in women, tend to be larger and have worse prognosis compared with other types of ACCs. We report the case of a 58-year-old woman who presented with bilateral breast enlargement and postmenopausal genital bleeding. She presented high estradiol (818 pg/mL - 25 times above upper normal limit for postmenopausal women) and testosterone (158 ng/dL - 2 times above upper normal limit) levels and no suppression of cortisol after overnight 1 mg dexamethasone test (12.5 µg/dL; normal reference value: < 1.8 µg/dL). The patient had no clinical features of cortisol excess. MRI showed a 12 cm tumor in the right adrenal. Clinical findings of bilateral breast enlargement and postmenopausal genital bleeding with no signs of hypercortisolism associated with hormonal findings of elevated estradiol and testosterone levels would indicate either an ovarian etiology or an adrenal etiology; however, in the context of plasma cortisol levels non-suppressive after dexamethasone test and the confirmation of an adrenal tumor by MRI, the diagnosis of an adrenal tumor with mixed hormonal secretion was made. The patient underwent an open right adrenalectomy and pathological examination revealed an ACC with a Weiss' score of 6. Estradiol and testosterone levels decreased to normal range soon after surgery. She was put on mitotane treatment as adjuvant therapy, but due to side effects, we were unable to up-titrate the dose and she never achieved serum mitotane dosage above the desired 14 µg/mL. The patient remained in good health without any local recurrence or metastasis until 5 years after surgery, when increased levels of estradiol (81 pg/mL - 2.5 times above upper normal limit) and testosterone (170 ng/dL - 2.1 times above upper normal limit) were detected. MRI revealed a retroperitoneal nodule measuring 1.8 × 1.2 cm. The pathological finding confirmed the recurrence of the estrogen-secreting ACC with a Weiss' score of 6. After the second procedure, patient achieved normal estrogen and androgen serum levels and since then she has been followed for 3 years. The overall survival was 8 years after the diagnosis. In conclusion, although extremely rare, a diagnosis of an estrogen-secreting ACC should be considered as an etiology in postmenopausal women presenting with bilateral breast enlargement, genital bleeding and increased pure or prevailing estrogen secretion.

LEARNING POINTS: Estrogen-secreting adrenocortical carcinomas are exceedingly rare in adults and account for 1-2% of adrenocortical carcinomas. Estrogen-secreting adrenal tumors can be present in females, but are even more rare, we found few cases described in the literature. In women, they present with precocious puberty or postmenopausal bleeding. Feminization in the context of an adrenal tumor is considered almost pathognomonic of malignancy. Feminizing ACCs tend to be larger and with worse prognosis compared with nonfeminizing ACCs.

PMID:33845455 | PMC:PMC7983493 | DOI:10.1530/EDM-20-0214

Ataxia telangiectasia mutated germline pathogenic variant in adrenocortical carcinoma

Fetched: April 11th, 2021, 5:00am GMT by Madeline B Torres

Cancer Genet. 2021 Mar 24;256-257:21-25. doi: 10.1016/j.cancergen.2021.03.003. Online ahead of print.

ABSTRACT

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare malignancy arising from the adrenal cortex. ACC carries a dismal prognosis and surgery offers the only chance for a cure. Germline pathogenic variants among certain oncogenes have been implicated in ACC. Here, we report the first case of ACC in a patient with a pathogenic variant in the Ataxia Telangiectasia Mutated (ATM) gene.

PATIENTS AND METHODS: A 56-year-old Caucasian woman with biopsy proven ACC deemed unresectable and treated with etoposide, doxorubicin and cisplatin (EDP), and mitotane presented to our institution for evaluation. The tumor specimen was examined pathologically, and genetic analyses were performed on the tumor and germline using next-generation sequencing.

RESULTS: Pathologic evaluation revealed an 18.0 × 14.0 × 9.0 cm low-grade ACC with tumor free resection margins. Immunohistochemistry stained for inhibin, melan-A, and chromogranin. ClinOmics analysis revealed a germline pathogenic deletion mutation of one nucleotide in ATM is denoted as c.1215delT at the cDNA level and p.Asn405LysfsX15 (N405KfsX15) at the protein level. Genomic analysis of the tumor showed loss of heterozygosity (LOH) of chromosome 11 on which the ATM resides.

CONCLUSION: ACC is an aggressive malignancy for which surgical resection currently offers the only curative option. Here we report a heterozygous loss-of-function mutation in germline DNA and LOH of ATM in tumor in an ACC patient, a classic two-hit scenario in a well-known cancer suppresser gene, suggesting a pathogenic role of the ATM gene in certain ACC cases.

PMID:33836455 | DOI:10.1016/j.cancergen.2021.03.003

Immunohistochemical analysis of ghrelin expression in various types of adrenal tumors

Fetched: April 10th, 2021, 5:00am GMT by Hanna Komarowska

Folia Histochem Cytobiol. 2021 Apr 9. doi: 10.5603/FHC.a2021.0009. Online ahead of print.

ABSTRACT

INTRODUCTION: Ghrelin, originally isolated from the endocrine cells of the gastric mucosa, is also expressed in many peripheral tissues, including normal adrenals and adrenocortical tumors. It was shown that ghrelin stimulates proliferation and inhibits apoptosis of adrenocortical cells. In the current study, we compared ghrelin expression at the protein level in various adrenal tumors. We analyzed whether immunoreactive ghrelin could be considered as a potential marker for different types of adrenal tumors.

MATERIAL AND METHODS: Study was carried out on 200 adrenal specimens arranged on microscope slide in tissue microarray format. We performed standardized immunohistochemical reactions with semiquantitative reaction intensity measurements.

RESULTS: At the protein level, the expression of ghrelin was significantly reduced in adrenocortical adenocarcinoma in relation to the control group and pheochromocytoma as well as cancer-adjacent normal adrenal tissue. In contrast, a relatively high ghrelin expression was found in pheochromocytoma compared to all analyzed groups, with the exception of cancer-adjacent normal adrenal tissue.

CONCLUSIONS: The ghrelin expression profile at the protein level may be associated with the type of adrenal tumors. In this context, our results suggest that adrenal immunoreactive ghrelin may be considered as a sensitive and specific marker for differentiating adrenocortical carcinoma from adrenocortical adenoma and pheochromocytoma.

PMID:33834452 | DOI:10.5603/FHC.a2021.0009

Permalink for 'A novel patient-derived cell line of adrenocortical carcinoma shows a pathogenic role of germline MUTYH mutation and high tumour mutational burden'

A novel patient-derived cell line of adrenocortical carcinoma shows a pathogenic role of germline MUTYH mutation and high tumour mutational burden

Fetched: April 9th, 2021, 5:00am GMT by Laura-Sophie Landwehr

Eur J Endocrinol. 2021 May 4;184(6):823-835. doi: 10.1530/EJE-20-1423.

ABSTRACT

BACKGROUND: The response of advanced adrenocortical carcinoma (ACC) to current chemotherapies is unsatisfactory and a limited rate of response to immunotherapy was observed in clinical trials. High tumour mutational burden (TMB) and the presence of a specific DNA signature are characteristic features of tumours with mutations in the gene MUTYH encoding the mutY DNA glycosylase. Both have been shown to potentially predict the response to immunotherapy. High TMB in an ACC cell line model has not been reported yet.

DESIGN AND METHODS: The JIL-2266 cell line was established from a primary ACC tumour, comprehensively characterised and oxidative damage, caused by a dysfunctional mutY DNA glycosylase, confirmed.

RESULTS: Here, we characterise the novel patient-derived ACC cell line JIL-2266, which is deficient in mutY-dependent DNA repair. JIL-2266 cells have a consistent STR marker profile that confirmed congruousness with primary ACC tumour. Cells proliferate with a doubling time of 41 ± 13 h. Immunohistochemistry revealed positivity for steroidogenic factor-1. Mass spectrometry did not demonstrate significant steroid hormone synthesis. JIL-2266 have hemizygous mutations in the tumour suppressor gene TP53 (c.859G>T:p.E287X) and MUTYH (c.316C>T:p.R106W). Exome sequencing showed 683 single nucleotide variants and 4 insertions/deletions. We found increased oxidative DNA damage in the cell line and the corresponding primary tumour caused by impaired mutY DNA glycosylase function and accumulation of 8-oxoguanine.

CONCLUSION: This model will be valuable as a pre-clinical ACC cell model with high TMB and a tool to study oxidative DNA damage in the adrenal gland.

PMID:33830941 | DOI:10.1530/EJE-20-1423

Permalink for 'Dual-layer dual-energy CT for characterization of adrenal nodules: can virtual unenhanced images replace true unenhanced acquisitions?'

Dual-layer dual-energy CT for characterization of adrenal nodules: can virtual unenhanced images replace true unenhanced acquisitions?

Fetched: April 9th, 2021, 5:00am GMT by Jinjin Cao

Abdom Radiol (NY). 2021 Apr 8. doi: 10.1007/s00261-021-03062-3. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the diagnostic performance of dual-layer dual-energy CT (dlDECT) in the evaluation of adrenal nodules.

METHODS: In this retrospective study, 66 patients with triphasic dlDECT (unenhanced, venous phase (VP), delayed phase (DP)) for suspected adrenal lesions were included. Virtual unenhanced images (VUE) were derived from VP acquisitions. Reference diagnoses were established with true unenhanced (TUE) attenuation, absolute washout, follow-up imaging and pathological data. Attenuation for adrenal lesions and abdominal tissues was acquired on TUE, VUE, VP and DP images. VUE and TUE attenuation were compared in all included tissues. Characterization of adrenal nodules based on TUE and VUE attenuation was investigated. ROC analysis was used to determine an adjusted threshold for diagnosing lipid-rich adenomas.

RESULTS: Seventy-three adrenal nodules (mean size: 18.9 ± 8.9 mm) were identified in 66 patients (38 females, 28 males; age: 61 ± 13 years) including adenoma (n = 65), metastases (n = 2), pheochromocytoma (n = 3), adrenocortical carcinoma (n = 1) and myelolipoma (n = 2). Mean attenuation of all included tissues except for the abdominal aorta (p = 0.11) was significantly higher in VUE compared to TUE images, including the attenuation of adrenal nodules (20.0 ± 17.2 vs. 7.1 ± 19.8; p < 0.05). Classification of adrenal adenomas as lipid-rich based on VUE attenuation ≤ 10 HU yielded a sensitivity/specificity of 0.2/1.0, while an adjusted threshold of ≤ 22 HU yielded a sensitivity/specificity of 0.82/0.85.

CONCLUSION: dlDECT-derived VUE images overestimated attenuation in adrenal nodules, resulting in low sensitivity for diagnosis of lipid-rich adenomas using the established 10 HU threshold. Based on an adjusted threshold (≤ 22 HU) a higher sensitivity was attained, yet at the expense of a lower specificity, warranting further validation.

PMID:33829304 | DOI:10.1007/s00261-021-03062-3

Adrenocortical cancer: morphological variants, immunohistochemical characteristics

Fetched: April 9th, 2021, 5:00am GMT by A V Tkachuk

Arkh Patol. 2021;83(3):10-18. doi: 10.17116/patol20218302110.

ABSTRACT

Adrenocortical cancer (ACC) is a rare endocrine malignancy of the adrenal cortex, which has an unfavorable prognosis and extremely aggressive clinical behavior in most cases. Nevertheless, cases of a more favorable disease course with late metastasis and slow progression have been described. In 2017, the International Agency for Research on Cancer (IARC) and the World Health Organization (WHO) in the 4^th edition of the Classification of Tumors of the Endocrine Organs identified histological variants of ACC, such as classical, oncocytic, myxoid, and sarcomatoid ones, indicating the morphological heterogeneity of this tumor.

OBJECTIVE: To provide a detailed description of the morphological variants of ACC with an emphasis on their histological characteristics and the expression of immunohistochemical markers.

MATERIALS AND METHODS: A total of 75 cases of ACC were analyzed in the adult population diagnosed as having the morphological variants in accordance with the International Histological Classification of Adrenal Tumors (WHO, 2017). Monoclonal antibodies to SF1, Inhibin A, Melan A, Ki-67, p53, and antimitochondrial antibodies were used for immunohistochemical diagnosis.

RESULTS: The classic, oncocytic, and myxoid subtypes of ACC were found in 51 (68%), 15 (20%), and 9 (12%) cases, respectively. The functional activity of the tumors was observed in 43% (n=18) in the classic variant of ACC; moreover, the clinical picture was manifested by the symptoms of hypercorticism (38%) and virilization (5%). There were no significant differences in hormonal activity between different morphological variants. The characteristics of the above histological variants of the tumor was determined with a description of growth patterns that can improve the diagnosis of ACC. The diagnosis of ACC can be confirmed by an immunohistochemical study; the required minimum panel of markers should include SF1, Melan A, and Inhibin A. The Ki-67 proliferative activity index showed significant differences (p=0.0056) when it was determined in the morphological variants of ACC.

CONCLUSION: Despite the determination of a minimal immunohistochemical panel to confirm the diagnosis of ACC, it is important to remember that each histological variant may be characterized by the different expression of immunohistochemical markers. The identification of morphological variants of ACC and the use of specific, sensitive, and prognostically significant immunohistochemical markers will allow clinicians and pathologists to more accurately judge the biological properties of this tumor and the clinical course of the disease.

PMID:33822549 | DOI:10.17116/patol20218302110

Permalink for 'Treatment of Pediatric Adrenocortical Carcinoma With Surgery, Retroperitoneal Lymph Node Dissection, and Chemotherapy: The Children's Oncology Group ARAR0332 Protocol'

Treatment of Pediatric Adrenocortical Carcinoma With Surgery, Retroperitoneal Lymph Node Dissection, and Chemotherapy: The Children's Oncology Group ARAR0332 Protocol

Fetched: April 7th, 2021, 5:00am GMT by Carlos Rodriguez-Galindo

J Clin Oncol. 2021 Apr 6:JCO2002871. doi: 10.1200/JCO.20.02871. Online ahead of print.

ABSTRACT

PURPOSE: Adrenocortical carcinoma (ACC) is a rare aggressive pediatric malignancy with distinct biology. Its treatment follows the principles developed for adults; pediatric-specific studies are scarce.

PATIENTS AND METHODS: Prospective single-arm risk-stratified interventional study. Study objectives were (1) to describe the outcome of patients with stage I ACC treated with adrenalectomy alone; (2) to describe the outcome of stage II patients (completely resected > 200 cc or > 100 g) treated with adrenalectomy and retroperitoneal lymph node dissection; and (3) to describe the outcome of patients with stage III or IV treated with mitotane and chemotherapy.

RESULTS: Between September 2006 and May 2013, 78 patients (77 eligible, 51 females) were enrolled. The 5-year event-free survival estimates for stages I (24 patients), II (15 patients), III (24 patients), and IV (14 patients) were 86.2%, 53.3%, 81%, and 7.1%, respectively. The corresponding 5-year overall survival estimates were 95.2%, 78.8%, 94.7%, and 15.6%, respectively. On univariate analysis, age, stage, presence of virilization, Cushing syndrome, or hypertension, germline TP53 status, and presence of a somatic ATRX mutation were associated with outcome. On multivariable analysis, only stage and age were significantly associated with outcome. The probabilities of mitotane and chemotherapy feasibility events were 10.5% and 31.6%, respectively.

CONCLUSION: Outcome for children with stage I ACC is excellent with surgery. Outcome for patients with stage II disease is inferior despite retroperitoneal lymph node dissection. Patients with stage III ACC have an excellent outcome combining surgery and chemotherapy. Patients with stage IV ACC are older and have a poor outcome; new treatments should be explored for this high-risk group. The combination of mitotane and chemotherapy as prescribed in ARAR0332 resulted in significant toxicity; one third of patients with advanced disease could not complete the scheduled treatment.

PMID:33822640 | DOI:10.1200/JCO.20.02871

Rare tumors: Retinoblastoma, nasopharyngeal cancer, and adrenocorticoid tumors

Fetched: April 6th, 2021, 5:00am GMT by Samir Patel

Pediatr Blood Cancer. 2021 May;68 Suppl 2:e28253. doi: 10.1002/pbc.28253.

ABSTRACT

The role of surgery, chemotherapy, and radiation therapy for retinoblastoma has evolved considerably over the years with the efficacy of intraarterial chemotherapy and the high incidence of secondary malignant neoplasms following radiation therapy. The use of spot scanning intensity-modulated proton therapy may reduce the risk of secondary malignancies. For pediatric nasopharyngeal carcinoma, the current standard of care is induction chemotherapy followed by chemoradiation therapy. For adrenocortical carcinoma, the mainstay of treatment is surgery and chemotherapy. The role of radiation therapy remains to be defined.

PMID:33818883 | DOI:10.1002/pbc.28253

Case Report: Ectopic Adrenocortical Carcinoma in the Ovary

Fetched: April 6th, 2021, 5:00am GMT by Wen-Hsuan Tsai

Front Endocrinol (Lausanne). 2021 Mar 19;12:662377. doi: 10.3389/fendo.2021.662377. eCollection 2021.

ABSTRACT

Adrenocortical carcinoma (ACC) is a rare malignancy with an incidence of 0.7-2.0 cases/million habitants/year. ACCs are rare and usually endocrinologically functional. We present the case of a 59-year-old woman who experienced abdominal fullness for 6 months and increased abdominal circumference. A large pelvic tumor was observed. She underwent cytoreductive surgery and the pathological test results revealed local tumor necrosis and prominent lympho-vascular invasion. Neuroendocrine carcinoma was the first impression, but positivity for synaptophysin, alpha-inhibin, transcription factor enhancer 3 (TFE-3), calretinin (focal), and CD56 (focal) and high Ki-67-labeling proliferating index (>80%) confirmed the diagnosis of ectopic ACC. Ectopic primary aldosteronism could not be excluded. However, we did not perform saline infusion test or captopril test due to poor performance status. When pathological test reports reveal neuroendocrine features not typically found in the organ being examined, IHC staining should be performed to rule out ectopic ACC. Whether the ectopic ACC is functional or not requires complete survey.

PMID:33815299 | PMC:PMC8018272 | DOI:10.3389/fendo.2021.662377

Giant Adrenocortical Carcinoma: A Case Report and Review of the Relevant Literature

Fetched: April 5th, 2021, 5:00am GMT by Ioannis Mantzoros

Am J Case Rep. 2021 Apr 4;22:e928875. doi: 10.12659/AJCR.928875.

ABSTRACT

BACKGROUND Adrenocortical carcinomas are rare and aggressive tumors often diagnosed as incidentalomas. The malignancy can present with abnormal hormone secretion or the tumor may be non-functioning and present as a palpable mass causing discomfort. Here, we present a case of an adrenal cortical carcinoma originally identified as an incidentaloma. CASE REPORT A 63-year-old woman presented with abdominal pain and discomfort. A large abdominal mass, occupying the left upper and lower quadrant, was palpated. Imaging revealed a mass occupying the left abdomen between the stomach and the spleen, applying pressure on the pylorus, duodenum, splenic vessels, and pancreas. The mass size was 21.2×13×14.6 cm. Hormonal investigations were normal. Surgical exploration was performed, and the tumor was excised. Pathological analysis revealed an adrenocortical carcinoma and the patient underwent adjuvant chemotherapy. Twelve months later, the carcinoma recurred. The patient underwent a second operation in which the recurrent mass was excised along with the tail of the pancreas and a small part of the left lobe of the liver. The postoperative period was uneventful, and the patient was discharged home on the 7th postoperative day. No further adjuvant therapy was applied. The patient remains disease-free 18 months after the reoperation. CONCLUSIONS Giant adrenocortical carcinomas, although rare, pose a challenge to the surgical team both diagnostically and therapeutically. Surgical excision with the appropriate oncologic support can guarantee excellent outcomes.

PMID:33813589 | PMC:PMC8033218 | DOI:10.12659/AJCR.928875

Methiothepin Increases Chemotherapy Efficacy against Resistant Melanoma Cells

Fetched: April 4th, 2021, 5:00am GMT by Nelly Durand

Molecules. 2021 Mar 26;26(7):1867. doi: 10.3390/molecules26071867.

ABSTRACT

We previously reported that methiothepin, a small molecule known as a nonselective serotonin 5-HT receptor antagonist, inhibited the doxorubicin efflux activity of the Hedgehog receptor Ptch1 and enhanced the cytotoxic, pro-apoptotic, anti-proliferative, and anti-clonogenic effects of doxorubicin on adrenocortical carcinoma cells. Here, we show that methiothepin also inhibits doxorubicin efflux and increases doxorubicin cytotoxicity in melanoma cells which endogenously overexpress Ptch1. Melanoma patients having the BRAF^V600E mutation are treated with vemurafenib, an inhibitor of BRAF^V600E, often in combination with trametinib, an inhibitor of MEK. Almost all patients ultimately acquire resistance to the treatment leading to disease progression. Here, we report that methiothepin overcomes the resistance of BRAF^V600E melanoma cells by enhancing the cytotoxicity of vemurafenib and trametinib on these cells leading to melanoma cells death. We observe that the addition of methiothepin to vemurafenib prevents migration of resistant melanoma cells more efficiently than vemurafenib alone. Our results provide an additional proof that Ptch1 drug efflux inhibition increases the effectiveness of anti-cancer treatments and overcomes resistance of melanoma cells expressing Ptch1.

PMID:33810240 | PMC:PMC8037503 | DOI:10.3390/molecules26071867

Immunotherapy in Adrenocortical Carcinoma: Predictors of Response, Efficacy, Safety, and Mechanisms of Resistance

Fetched: April 4th, 2021, 5:00am GMT by Marta Araujo-Castro

Biomedicines. 2021 Mar 16;9(3):304. doi: 10.3390/biomedicines9030304.

ABSTRACT

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with limited treatment options in the advanced stages. Immunotherapy offers hope for altering the orthodox management of cancer, and its role in advanced ACC has been investigated in different studies. With the aim clarifying the role of immunotherapy in ACC we performed a comprehensive review about this topic focusing on the predictors of response, efficacy, safety, and the mechanisms of resistance. Five clinical trials with four immune checkpoint inhibitors (pembrolizumab, avelumab, nivolumab, and ipilimumab) have investigated the role of immunotherapy in advanced ACC. Despite, the different primary endpoints used in these studies, the reported rates of overall response rate and progression free survival were generally poor. Three main potential markers of response to immunotherapy in ACC have been described: Expression of PD-1 and PD-L1, microsatellite instability and tumor mutational burden. However, none of them has been validated in prospective studies. Several mechanisms of ACC immunoevasion may be responsible of immunotherapy failure, and a greater knowledge of these mechanisms might lead to the development of new strategies to overcome the immunotherapy resistance. In conclusion, although currently the role of immunotherapy is limited, the identification of immunological markers of response and the implementation of strategies to avoid immunotherapy resistance could improve the efficacy of this therapy.

PMID:33809752 | PMC:PMC8002272 | DOI:10.3390/biomedicines9030304

Preoperative Detection of Liver Involvement by Right-Sided Adrenocortical Carcinoma Using CT and MRI

Fetched: April 4th, 2021, 5:00am GMT by Alice Kedra

Cancers (Basel). 2021 Mar 31;13(7):1603. doi: 10.3390/cancers13071603.

ABSTRACT

The major prognosis factor of adrenocortical carcinoma (ACC) is the completeness of surgery. The aim of our study was to identify preoperative imaging features associated with direct liver involvement (DLI) by right-sided ACC. Two radiologists, blinded to the outcome, independently reviewed preoperative CT and MRI examinations for eight signs of DLI, in patients operated for right-sided ACC and retrospectively included from November 2007 to January 2020. DLI was confirmed using surgical and histopathological findings. Kappa values were calculated. Univariable and multivariable analyses were performed by using a logistic regression model. Receiver operating characteristic (ROC) curves were built for CT and MRI. Twenty-nine patients were included. Seven patients had DLI requiring en bloc resection. At multivariable analysis, focal ACC bulge was the single independent sign associated with DLI on CT (OR: 60.00; 95% CI: 4.60-782.40; p < 0.001), and ACC contour disruption was the single independent sign associated with DLI on MRI (OR: 126.00; 95% CI: 6.82-2328.21; p < 0.001). Both signs were highly reproducible, with respective kappa values of 0.85 and 0.91. The areas under ROC curves of MRI and CT models were not different (p = 0.838). Focal ACC bulge on CT and ACC contour disruption on MRI are independent and highly reproducible signs, strongly associated with DLI by right-sided ACC on preoperative imaging. MRI does not improve the preoperative assessment of DLI by comparison with CT.

PMID:33807178 | PMC:PMC8036813 | DOI:10.3390/cancers13071603

Sex Differences on Mitotane Concentration and Treatment Outcome in Patients with Adrenocortical Carcinoma

Fetched: April 4th, 2021, 5:00am GMT by Sarah Allegra

Life (Basel). 2021 Mar 23;11(3):266. doi: 10.3390/life11030266.

ABSTRACT

(1) Background: In clinical settings, data regarding sex are rarely investigated. In women, factors such as body size and composition, hormonal variations, metabolism, and access to care systems and therapy could strongly influence the pharmacological management and the outcome of the therapy. To underline this sex-related difference, we retrospectively collected data from adrenocortical carcinoma patients treated with mitotane, and then evaluated sex-related pharmacokinetics parameters. (2) Methods: A fully validated chromatographic method was used to quantify mitotane concentration in plasma collected from adult patients, also considering the active metabolite ortho,para,dichlorodiphenylethene (o,p'-DDE). Statistical analyses were used to evaluate the sex influence on drugs pharmacokinetics. (3) Results: We found that sex resulted as predictive factor of plasma mitotane and o,p'-DDE concentrations and significantly influenced the attainment of the therapeutic target of mitotane, implying that female sex could be a risk factor of treatment failure. (4) Conclusions: These results suggest that mitotane therapy should be modulated according to patient sex. Furthermore, the proposed approach could contribute to facilitating and disseminating sex-specific pharmacology.

PMID:33807024 | PMC:PMC8004922 | DOI:10.3390/life11030266

Angiogenesis in the Normal Adrenal Fetal Cortex and Adrenocortical Tumors

Fetched: April 4th, 2021, 5:00am GMT by Sofia S Pereira

Cancers (Basel). 2021 Mar 1;13(5):1030. doi: 10.3390/cancers13051030.

ABSTRACT

Angiogenesis plays an important role in several physiological and pathological processes. Pharmacological angiogenesis modulation has been robustly demonstrated to achieve clinical benefits in several cancers. Adrenocortical carcinomas (ACC) are rare tumors that often have a poor prognosis. In addition, therapeutic options for ACC are limited. Understanding the mechanisms that regulate adrenocortical angiogenesis along the embryonic development and in ACC could provide important clues on how these processes could be pharmacologically modulated for ACC treatment. In this report, we performed an integrative review on adrenal cortex angiogenesis regulation in physiological conditions and ACC. During embryonic development, adrenal angiogenesis is regulated by both VEGF and Ang-Tie signaling pathways. In ACC, early research efforts were focused on VEGF signaling and this pathway was identified as a good prognostic factor and thus a promising therapeutic target. However, every clinical trial so far conducted in ACC using VEGF pathway- targeting drugs, alone or in combination, yielded disappointing results. In contrast, although the Ang-Tie pathway has been pointed out as an important regulator of fetal adrenocortical angiogenesis, its role is yet to be explored in ACC. In the future, further research on the role and efficacy of modulating both Ang-Tie and VEGF pathways in ACC is needed.

PMID:33804534 | PMC:PMC7957756 | DOI:10.3390/cancers13051030

The Role of Immunohistochemical Markers for the Diagnosis and Prognosis of Adrenocortical Neoplasms

Fetched: April 4th, 2021, 5:00am GMT by Anna Angelousi

J Pers Med. 2021 Mar 15;11(3):208. doi: 10.3390/jpm11030208.

ABSTRACT

Adrenal cortical carcinoma (ACC) is a rare cancer with poor prognosis that needs to be distinguished from adrenocortical adenomas (ACAs). Although, the recently developed transcriptome analysis seems to be a reliable tool for the differential diagnosis of adrenocortical neoplasms, it is not widely available in clinical practice. We aim to evaluate histological and immunohistochemical markers for the distinction of ACCs from ACAs along with assessing their prognostic role. Clinical data were retrospectively analyzed from 37 patients; 24 archived, formalin-fixed, and paraffin-embedded ACC samples underwent histochemical analysis of reticulin and immunohistochemical analysis of p27, p53, Ki-67 markers and were compared with 13 ACA samples. Weiss and Helsinki scores were also considered. Kaplan-Meier and univariate Cox regression methods were implemented to identify prognostic effects. Altered reticulin pattern, Ki-67% labelling index and overexpression of p53 protein were found to be useful histopathological markers for distinguishing ACAs from ACCs. Among the studied markers, only pathological p53 nuclear protein expression was found to reach statistically significant association with poor survival and development of metastases, although in a small series of patients. In conclusion, altered reticulin pattern and p53/Ki-67 expression are useful markers for distinguishing ACCs from ACAs. Immunohistopathology alone cannot discriminate ACCs with different prognosis and it should be combined with morphological criteria and transcriptome analysis.

PMID:33804047 | PMC:PMC8001501 | DOI:10.3390/jpm11030208

Adrenocortical Carcinoma

Fetched: April 4th, 2021, 5:00am GMT by Alfredo Berruti

Cancers (Basel). 2021 Mar 3;13(5):1077. doi: 10.3390/cancers13051077.

ABSTRACT

Adrenocortical carcinoma (ACC) is an extremely rare disease, the incidence of which is 0 [...].

PMID:33802418 | PMC:PMC7959308 | DOI:10.3390/cancers13051077

Prognostic Alternative mRNA Splicing in Adrenocortical Carcinoma

Fetched: March 30th, 2021, 5:00am GMT by Weiwei Liang

Front Endocrinol (Lausanne). 2021 Mar 12;12:538364. doi: 10.3389/fendo.2021.538364. eCollection 2021.

ABSTRACT

BACKGROUND: This paper aims to identify alternative RNA splicing landscape and its prognostic value in adrenocortical carcinoma.

METHODS: The alternative splicing events data with corresponding clinical information data of 79 ACC patients were obtained from the Cancer Genome Atlas and SpliceSeq package. Prognosis-associated AS events by using univariate Cox regression analysis were selected. Gene functional enrichment analysis demonstrated the potential pathways enriched by survival-associated AS. Prognosis-related splicing events were submitted to develop moderate predictors using Lasso regression model.

RESULTS: One thousand five survival-associated alternative splicing events were identified. The prognostic genes included ATXN2L, MEIS1, IKBKB, COX4I1. Functional enrichment analysis suggested that prognostic splicing events are associated with Wnt signaling pathway. A prediction model including 12 alternative splicing events was constructed by Lasso regression using train set. ROC analysis showed good performance of the prediction model in test set. Then, a nomogram integrating the clinical-pathological factors and riskscore was constructed for predicting 1- and 3-year survival rate.

CONCLUSION: Our data provide a comprehensive bioinformatics analysis of AS events in ACC, providing biomarkers for disease progression and a potentially rich source of novel therapeutic targets.

PMID:33776902 | PMC:PMC7994755 | DOI:10.3389/fendo.2021.538364

Delayed identification of adolescent adrenal cortical carcinoma initially diagnosed as polycystic ovary syndrome

Fetched: March 30th, 2021, 5:00am GMT by Liu Ziqin

J Pediatr Adolesc Gynecol. 2021 Mar 26:S1083-3188(21)00154-6. doi: 10.1016/j.jpag.2021.03.004. Online ahead of print.

ABSTRACT

BACKGROUND: Adrenocortical carcinoma is a rare, isolated malignancy.

CASE: A 13-year-old girl presented with secondary amenorrhea, hirsutism, and hypertension. Her clinical manifestations were interpreted as polycystic ovary syndrome and hyperinsulinemia. The rapid progression of this pubertal girl's virilization should have, but did not draw clinical attention to her malignancy. Because her condition worsened, she ultimately was transferred to our hospital because of an abdominal mass. She was diagnosed with a very large adrenal cortical carcinoma with pulmonary metastasis. The child was in the advanced stage and presented adrenal crisis after chemotherapy and mitotane treatment.

SUMMARY AND CONCLUSION: Rapidly progressive masculinization, with a marked increase in adrenal-derived androgens, might indicate rare adrenal neoplasms.

PMID:33775909 | DOI:10.1016/j.jpag.2021.03.004

Adrenal tumors of different types with or without tumor thrombus invading the inferior vena cava: An evaluation of 33 cases

Fetched: March 28th, 2021, 5:00am GMT by Gaetano Ciancio

Surg Oncol. 2021 Mar 19;37:101544. doi: 10.1016/j.suronc.2021.101544. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Adrenal tumors with/out tumor thrombus (TT) in the inferior vena cava (IVC) pose a challenge to the surgeon due to the potential of massive hemorrhage and tumor thromboembolism. We report our experience in managing different types of adrenal tumors.

METHODS: From 11/1996-5/2015, 33 patients underwent resection of adrenal tumors with/without TT/IVC in 8 and 25 patients, respectively. Transplant-based (TB) techniques were utilized to resect the tumors. Intra-operative as estimated blood loss (EBL) and cardiopulmonary bypass (CPB) use; post-operative as length of hospital stay (LOS); and actuarial survival outcomes were recorded.

RESULTS: Median EBL was 200 cc (10-8,000), tumor size was 9.0 cm (4-25), and LOS was 7days (5-60). Adrenocortical carcinoma (ACC,11/33) was the commonest type. Three ACC/level IV TT/IVC underwent CPB to extract TT from the right atrium(n = 1), right atrium and right ventricle(n = 1), and right atrium and right pulmonary artery(n = 1), respectively. A complete resection of the adrenal tumors was achieved in all patients, and no deaths were observed in the immediate postoperative period. With a median follow-up of 60 (range: 18-120) months, 4/11 ACC patients have died of their disease. Actuarial survival for ACC patients at 60 months was 57.1 ± 16.4%.

CONCLUSIONS: An aggressive surgical approach is the only hope for curing large adrenal tumors with/without TT/IVC. TB techniques provide excellent exposure to the retroperitoneal space and safe removal of large adrenal masses.

PMID:33773281 | DOI:10.1016/j.suronc.2021.101544

Permalink for 'Analysis of m6A-Related Signatures in the Tumor Immune Microenvironment and Identification of Clinical Prognostic Regulators in Adrenocortical Carcinoma'

Analysis of m6A-Related Signatures in the Tumor Immune Microenvironment and Identification of Clinical Prognostic Regulators in Adrenocortical Carcinoma

Fetched: March 23rd, 2021, 5:00am GMT by Yi Jin

Front Immunol. 2021 Mar 3;12:637933. doi: 10.3389/fimmu.2021.637933. eCollection 2021.

ABSTRACT

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a high rate of mortality and recurrence. N6-methyladenosine methylation (m6A) is the most common modification to affect cancer development, but to date, the potential role of m6A regulators in ACC prognosis is not well understood. In this study, we systematically analyzed 21 m6A regulators in ACC samples from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. We identified three m6A modification patterns with different clinical outcomes and discovered a significant relationship between diverse m6A clusters and the tumor immune microenvironment (immune cell types and ESTIMATE algorithm). Additionally, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) revealed that the m6A clusters were strongly associated with immune infiltration in the ACC. Next, to further explore the m6A prognostic signatures in ACC, we implemented Lasso (Least Absolute Shrinkage and Selection Operator) Cox regression to establish an eight-m6A-regulator prognostic model in the TCGA dataset, and the results showed that the model-based high-risk group was closely correlated with poor overall survival (OS) compared with the low-risk group. Subsequently, we validated the key modifications in the GEO datasets and found that high HNRNPA2B1 expression resulted in poor OS and event-free survival (EFS) in ACC. Moreover, to further decipher the molecular mechanisms, we constructed a competing endogenous RNA (ceRNA) network based on HNRNPA2B1, which consists of 12 long noncoding RNAs (lncRNAs) and 1 microRNA (miRNA). In conclusion, our findings indicate the potential role of m6A modification in ACC, providing novel insights into ACC prognosis and guiding effective immunotherapy.

PMID:33746977 | PMC:PMC7966528 | DOI:10.3389/fimmu.2021.637933

Thermal ablation in adrenal disorders: a discussion of the technology, the clinical evidence and the future

Fetched: March 21st, 2021, 5:00am GMT by Padraig Donlon

Curr Opin Endocrinol Diabetes Obes. 2021 Jun 1;28(3):291-302. doi: 10.1097/MED.0000000000000627.

ABSTRACT

PURPOSE OF REVIEW: To summarise the emerging role of thermal ablation as a therapeutic modality in the management of functioning adrenal tumours and metastases to the adrenal gland.

RECENT FINDINGS: Observational evidence has demonstrated the benefit of thermal ablation in (i) resolving adrenal endocrinopathy arising from benign adenomas, (ii) treating solitary metastases to the adrenal and (iii) controlling metastatic adrenocortical carcinoma and phaeochromocytoma/paraganglioma.

SUMMARY: Microwave thermal ablation offers a promising, minimally invasive therapeutic modality for the management of functioning adrenocortical adenomas and adrenal metastases. Appropriate technological design, treatment planning and choice of imaging modality are necessary to overcome technical challenges associated with this emerging therapeutic approach.

PMID:33741778 | DOI:10.1097/MED.0000000000000627

Steroid sulfation in adrenal tumors

Fetched: March 20th, 2021, 5:00am GMT by Jonathan Wolf Mueller

J Clin Endocrinol Metab. 2021 Mar 19:dgab182. doi: 10.1210/clinem/dgab182. Online ahead of print.

ABSTRACT

CONTEXT: The adrenal cortex produces specific steroid hormones including steroid sulfates such as dehydroepiandrosterone sulfate (DHEAS), the most abundant steroid hormone in the human circulation. Steroid sulfation involves a multi-step enzyme machinery that may be impaired by inborn errors of steroid metabolism. Emerging data suggest a role of steroid sulfates in the pathophysiology of adrenal tumors and as potential biomarkers.

EVIDENCE ACQUISITION: Selective literature search using "steroid", "sulfat*", "adrenal", "transport", "mass spectrometry" and related terms in different combinations.

EVIDENCE SYNTHESIS: A recent study highlighted the tissue abundance of estrogen sulfates to be of prognostic impact in adrenocortical carcinoma tissue samples using MALDI mass spectrometry imaging. General mechanisms of sulfate uptake, activation and transfer to substrate steroids are reasonably well understood. Key aspects of this pathway however have not been investigated in detail in the adrenal; these include the regulation of substrate specificity and the secretion of sulfated steroids. Both for the adrenal and targeted peripheral tissues, steroid sulfates may have relevant biological actions beyond their cognate nuclear receptors after desulfation. Impaired steroid sulfation such as low DHEAS in Cushing adenomas is of diagnostic utility, but more comprehensive studies are lacking. In bioanalytics, the requirement of deconjugation for gas-chromatography/mass-spectrometry has precluded the study of steroid sulfates for a long time. This limitation may be overcome by liquid-chromatography/tandem-mass-spectrometry.

CONCLUSIONS: A role of steroid sulfation in the pathophysiology of adrenal tumors has been suggested and a diagnostic utility of steroid sulfates as biomarkers is likely. Recent analytical developments may target sulfated steroids specifically.

PMID:33739426 | DOI:10.1210/clinem/dgab182

Current Status and Future Targeted Therapy in Adrenocortical Cancer

Fetched: March 19th, 2021, 5:00am GMT by George Alyateem

Front Endocrinol (Lausanne). 2021 Mar 1;12:613248. doi: 10.3389/fendo.2021.613248. eCollection 2021.

ABSTRACT

Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis. The current treatment standards include complete surgical resection for localized resectable disease and systemic therapy with mitotane alone or in combination with etoposide, doxorubicin, and cisplatin in patients with advanced ACC. However, the efficacy of systemic therapy in ACC is very limited, with high rates of toxicities. The understanding of altered molecular pathways is critically important to identify effective treatment options that currently do not exist. In this review, we discuss the results of recent advanced in molecular profiling of ACC with the focus on dysregulated pathways from various genomic and epigenetic dysregulation. We discuss the potential translational therapeutic implication of molecular alterations. In addition, we review and summarize the results of recent clinical trials and ongoing trials.

PMID:33732213 | PMC:PMC7957049 | DOI:10.3389/fendo.2021.613248

Expression patterns and prognostic value of m6A RNA methylation regulators in adrenocortical carcinoma

Fetched: March 18th, 2021, 5:00am GMT by Yang Fu

Medicine (Baltimore). 2021 Mar 12;100(10):e25031. doi: 10.1097/MD.0000000000025031.

ABSTRACT

Adrenocortical carcinoma (ACC) is considered a rare cancer with poor prognosis. We used public datasets from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases to assess the relationships between N6-methyladenosine (m6A)-related genes and ACC.We used the Wilcoxon signed-rank test to compare m6A-related gene expression in ACC tissues with that in normal tissues. Then, ACC patients were grouped based on a cluster analysis of m6A-related gene expression. m6A-related genes that were significantly associated with survival were incorporated into a risk signature, and 2 groups were divided according to median risk score. Fisher exact tests were utilized to analyze differences in clinical variables between groups. We compared the overall survival (OS) rates of the groups by means of Kaplan-Meier curves and Cox regression analyses.We found that RBM15, ZC3H3, YTDHF1, YTDHF2, and ALBH5 were overexpressed in ACC and that KIAA1429, YTHDC1, HNRNPC, WTAP, METTL3, and FTO were down regulated in ACC. In addition, membership in cluster 2 or the high-risk group was associated with advanced clinical factors and poor prognosis. The univariable and multivariable Cox regression analyses showed that risk score can be considered an independent prognostic factor for ACC.We found that the expression of m6A-related genes could be used as an independent prognostic factor in ACC. However, the current study has some limitations, and further studies of m6A-related genes in ACC are needed.

PMID:33725886 | PMC:PMC7969304 | DOI:10.1097/MD.0000000000025031

Permalink for 'Clinical Prognostic Factors in Patients With Metastatic Adrenocortical Carcinoma Treated With Second Line Gemcitabine Plus Capecitabine Chemotherapy'

Clinical Prognostic Factors in Patients With Metastatic Adrenocortical Carcinoma Treated With Second Line Gemcitabine Plus Capecitabine Chemotherapy

Fetched: March 16th, 2021, 5:00am GMT by Salvatore Grisanti

Front Endocrinol (Lausanne). 2021 Feb 24;12:624102. doi: 10.3389/fendo.2021.624102. eCollection 2021.

ABSTRACT

Gemcitabine plus Capecitabine (Gem/Cape) is a frequently adopted second line chemotherapy for metastatic adrenocortical carcinoma (ACC), but only a minority of patients is destined to obtain a clinical benefit. The identification of baseline predictive factors of efficacy is relevant. We retrospectively analyzed clinical data from 50 consecutive patients with metastatic progressing ACC treated between 2011 and 2019. Patients received intravenous Gemcitabine and oral Capecitabine on a metronomic schedule. Previous mitotane therapy was maintained. Clinical benefit (partial response + stable disease) at 4 months was 30%, median progression-free survival (PFS) and disease-specific survival (DSS) from Gem/Cape start were 3 and 8 months, respectively. Among clinical variables evaluated before the start of Gem/Cape, presence of ECOG performance status ≥1 [HR 6.93 95% confidence interval (CI) 0.03-0.54, p.004] and neutrophil-to-lymphocyte ratio (NLR) ≥5 [HR 3.88, 95% (CI) 0.81-0.90, p.003] were independent indicators of poor PFS at multivariate analysis. Conversely, surgery of primary tumor, the presence of lung or lymph-node metastases, blood mitotane level, anemia, and the Advanced Lung cancer Inflammation index (ALI) failed to be independently associated. This study confirms that the Gem/Cape schedule is modestly active in heavily pretreated ACC patients (28% received at least two previous chemotherapy lines). NLR and performance status (PS) are easily available clinical parameters that are helpful to identify patients not likely to derive significant advantage from Gem/Cape chemotherapy.

PMID:33716976 | PMC:PMC7943871 | DOI:10.3389/fendo.2021.624102

Approach to patients with European Network for the Study of Adrenal Tumor stages I and II adrenocortical carcinomas

Fetched: March 13th, 2021, 5:00am GMT by Darko Kastelan

Curr Opin Endocrinol Diabetes Obes. 2021 Jun 1;28(3):265-270. doi: 10.1097/MED.0000000000000626.

ABSTRACT

PURPOSE OF REVIEW: Adrenocortical carcinoma (ACC) is a rare tumor with variable prognosis depending mostly on the disease stage and tumor grade. The staging system proposed by the European Network for the Study of Adrenal Tumors has a reliable prognostic potential and defines ACC stages I-IV. Due to the absence of extraadrenal tissue invasion, patients with stage I-II have a lower recurrence rate and better prognosis. This article elaborates on the current understanding of the clinical approach to this group of patients.

RECENT FINDINGS: Concerning the treatment, complete surgical resection of the tumor provides the only chance for cure. However, even after tumor removal, the risk of recurrence remains high and the main predictors of recurrence include tumor stage, grade (measured by Ki-67 proliferative index), and the tumor resection status. Adjuvant mitotane and/or adjuvant radiotherapy should be considered in patients with high risk of recurrence taking into account potential harmful effects of such treatment. Accordingly, careful selection of patients who may benefit from adjuvant treatment is of the utmost importance both for improving disease outcome and for avoiding potential overtreatment in patients who are at low risk of disease recurrence.

SUMMARY: Many aspects of the management of patients with ACC stages I and II are not entirely evidence-based, and treatment decisions rely mostly on expert opinions and data from retrospective studies. Therefore, the treatment of these patients should be restricted to specialized centers with high expertise in ACC.

PMID:33709971 | DOI:10.1097/MED.0000000000000626

Genomic and Clinical Correlates of Adrenocortical Carcinoma in an Adult Patient with Li-Fraumeni Syndrome: A Case Report

Fetched: March 12th, 2021, 5:00am GMT by Suraya Bondy

Curr Oncol. 2020 Dec 31;28(1):226-232. doi: 10.3390/curroncol28010025.

ABSTRACT

Li-Fraumeni Syndrome (LFS) is defined by germline mutations of the p53 tumour suppressor gene. Adrenocortical carcinoma (ACC) is a rare aggressive malignancy that is commonly associated with LFS. Most LFS-linked ACC cases occur in children, and limited research has been dedicated to the clinical outcomes and genomics of adult cases with LFS-linked ACC. We report on a 34-year-old female who was diagnosed with three separate malignancies: stage III invasive ductal carcinoma of the right breast, metastatic ACC from the right adrenal gland, and grade 2 pleomorphic sarcoma of the left hand. Her invasive breast ductal carcinoma was treated with neoadjuvant chemotherapy, and she received a bilateral mastectomy after her LFS was confirmed with genetic blood testing. Adrenal ACC was initially treated with a right nephrectomy and adrenalectomy, followed by adjuvant mitotane and two lines of chemotherapy after disease recurrence. Her hand sarcoma was treated by second ray amputation. Further, we conducted deep next-generation sequencing of each of her unique tumour tissue samples using FoundationONE CDx. A whole-genome shot capture followed by in vitro sequencing performed by the Illumina^® HiSeq platform revealed a germline P191fs*18 TP53 mutation across all three tissue samples. This case provides insight into the genomics and clinical characteristics of LFS-linked adult-onset ACC and demonstrated that p53 mutations were preserved throughout each malignancy, without apparent treatment pressures on genomic profiling. This case reinforces the critical importance of adopting best practices for LFS, which include the implementation of highly vigilant screening and management of care in a multidisciplinary setting.

PMID:33704190 | PMC:PMC7900890 | DOI:10.3390/curroncol28010025

Permalink for 'Development and Validation of an m6A RNA Methylation Regulators-Based Signature for Predicting the Prognosis of Adrenocortical Carcinoma'

Development and Validation of an m6A RNA Methylation Regulators-Based Signature for Predicting the Prognosis of Adrenocortical Carcinoma

Fetched: March 12th, 2021, 5:00am GMT by Chengquan Shen

Front Endocrinol (Lausanne). 2021 Feb 22;12:568397. doi: 10.3389/fendo.2021.568397. eCollection 2021.

ABSTRACT

BACKGROUND: Adrenocortical carcinoma (ACC) is an aggressive and rare neoplasm that originates from the cortex of the adrenal gland. N6-methyladenosine (m6A) RNA methylation, the most common form of mRNA modification, has been reported to be correlated with the occurrence and development of the malignant tumor. This study aims to identify the significance of m6A RNA methylation regulators in ACC and construct a m6A based signature to predict the prognosis of ACC patients.

MATERIALS AND METHODS: RNA-seq data from The Cancer Genome Atlas (TCGA) database was used to identify the expression level of m6A RNA methylation regulators in ACC. An m6A based signature was further constructed and its prognostic and predictive values were assessed by survival analysis and nomogram.

RESULTS: 11 m6A RNA regulators were differentially expressed in ACC and three m6A RNA regulators were finally selected in a signature to predict the prognosis of ACC patients. Survival analysis indicated that high risk scores were closely related to poor survival outcomes in ACC patients. Univariate and multivariate Cox regression analyses demonstrated that the m6A based signature was an independent prognostic factor for ACC patients. A nomogram with clinical factors and the m6A based signature was also constructed to superiorly predict the prognosis of ACC patients. The expression levels of m6A RNA methylation regulators, which were contained in the signature, were also verified in human ACC tissues and normal tissues by using vitro experiments.

CONCLUSION: We identified and validated an m6A based signature, which can be used as an independent prognostic factor in evaluating the prognosis of ACC patients. Further clinical trials and experimental explorations are needed to confirm our observations and mechanisms underlying prognostic values of these m6A RNA methylation regulators in ACC.

PMID:33692753 | PMC:PMC7937949 | DOI:10.3389/fendo.2021.568397

Permalink for 'Long-term outcomes in patients with advanced adrenocortical carcinoma after image-guided locoregional ablation or embolization'

Long-term outcomes in patients with advanced adrenocortical carcinoma after image-guided locoregional ablation or embolization

Fetched: March 10th, 2021, 5:00am GMT by Michal Mauda-Havakuk

Cancer Med. 2021 Apr;10(7):2259-2267. doi: 10.1002/cam4.3740. Epub 2021 Mar 9.

ABSTRACT

BACKGROUND: To evaluate outcomes and survival rates in patients with metastatic adrenocortical carcinoma (ACC) who were treated with image-guided locoregional treatments (IGLTs).

PURPOSE: To evaluate the overall survival (OS) and clinical impact of IGLT in the management of patients with advanced metastatic ACC.

METHODS: Retrospective review of 39 patients treated with IGLT between 1999 and 2018 was performed. Short- and long-term efficacy of treatments were defined based upon imaging and clinical data. Subgroup survival analysis was performed on patients with metastatic disease at diagnosis (N = 17) and compared with the same stage group from the most recent National Cancer Database (NCDB) report. Statistical analysis was performed using Cox proportional hazards model.

RESULTS: Treatments were performed at different anatomic sites including liver (N = 46), lung (N = 14), retroperitoneum (N = 5), bone (N = 4), subcutaneous (N = 2), and intracaval (N = 1). Radiofrequency, microwave, cryoablation, or a combination of two modalities (45, 18, 3, 3, respectively) were used in 69 ablation sessions. Intra-arterial procedures were performed in 12 patients in 18 treatment cycles (range 1-3 per patient). As of a 2019 analysis, 11 patients were alive with a mean follow-up of 169 months (range 63-292 months) from diagnosis. Two- and 5-year OS rates for all patients were 84.5% and 51%, respectively, and 76.5% and 59% for patients with metastatic disease at diagnosis (N = 17). This compares favorably with an NCDB report of 35% 5-year survival rate for patients with metastatic disease. Female gender and longer time from diagnosis to first IGLT were found to be predictors of prolonged survival with hazard ratios of 0.23 (p < 0.001) and 0.66 (p = 0.001), respectively.

CONCLUSION: IGLT may be associated with prolonged life expectancy in select patients with metastatic ACC.

PMID:33687146 | PMC:PMC7982621 | DOI:10.1002/cam4.3740

CD96 Correlates With Immune Infiltration and Impacts Patient Prognosis: A Pan-Cancer Analysis

Fetched: March 9th, 2021, 5:00am GMT by Wenrui Ye

Front Oncol. 2021 Feb 19;11:634617. doi: 10.3389/fonc.2021.634617. eCollection 2021.

ABSTRACT

BACKGROUND: Immunotherapy has significantly improved patient outcomes, but encountered obstacles recently. CD96, a novel immune checkpoint expressed on T cells and natural killer (NK) cells, is essential for regulating immune functions. However, how CD96 correlating with immune infiltration and patient prognosis in pan-cancer remains unclear.

METHODS: HPA, TCGA, GEO, GTEx, Oncomine, TIMER2.0, PrognoScan, Linkedomics, Metascape, and GEPIA2 databases were used to analyze CD96 in cancers. Visualization of data was mostly achieved by R language, version 4.0.2.

RESULTS: In general, CD96 was differentially expressed between most cancer and adjacent normal tissues. CD96 significantly impacted the prognosis of diverse cancers. Especially, high CD96 expression was associated with poorer overall survival (OS) and disease-specific survival (DSS) in the TCGA lower grade glioma (LGG) cohort (OS, HR = 2.18, 95% CI = 1.79-2.66, P < 0.001). The opposite association was significantly observed in skin cutaneous melanoma (SKCM) cohort (OS, HR = 0.96, 95% CI = 0.94-0.98, P < 0.001). Notably, SKCM samples demonstrated the highest CD96 mutation frequency among all cancer types. Furthermore, in most cancers, CD96 expression level was significantly correlated with expression levels of recognized immune checkpoints and abundance of multiple immune infiltrates including CD8+ T cells, dendric cells (DCs), macrophages, monocytes, NK cells, neutrophils, regulatory T cells (Tregs), and follicular helper T cells (Tfh). CD96 was identified as a risk factor, protective factor, and irrelevant variable in LGG, SKCM and adrenocortical carcinoma (ACC), respectively. CD96 related genes were involved in negative regulation of leukocyte in LGG, however, involved in multiple positive immune processes in SKCM. Furthermore, CD96 was significantly associated with particular immune marker subsets. Importantly, it strongly correlated with markers of type 1 helper T cell (Th1) in SKCM, but not in LGG or ACC either.

CONCLUSIONS: CD96 participates in diverse immune responses, governs immune cell infiltration, and impacts malignant properties of various cancer types, thus standing as a potential biomarker for determining patient prognosis and immune infiltration in multiple cancers, especially in glioma and melanoma.

PMID:33680972 | PMC:PMC7935557 | DOI:10.3389/fonc.2021.634617

Radiomics: a new tool to differentiate adrenocortical adenoma from carcinoma

Fetched: March 9th, 2021, 5:00am GMT by F Torresan

BJS Open. 2021 Jan 8;5(1):zraa061. doi: 10.1093/bjsopen/zraa061.

ABSTRACT

BACKGROUND: The main challenge in the management of indeterminate incidentally discovered adrenal tumours is to differentiate benign from malignant lesions. In the absence of clear signs of invasion or metastases, imaging techniques do not always precisely define the nature of the mass. The present pilot study aimed to determine whether radiomics may predict malignancy in adrenocortical tumours.

METHODS: CT images in unenhanced, arterial, and venous phases from 19 patients who had undergone resection of adrenocortical tumours and a cohort who had undergone surveillance for at least 5 years for incidentalomas were reviewed. A volume of interest was drawn for each lesion using dedicated software, and, for each phase, first-order (histogram) and second-order (grey-level colour matrix and run-length matrix) radiological features were extracted. Data were revised by an unsupervised machine learning approach using the K-means clustering technique.

RESULTS: Of operated patients, nine had non-functional adenoma and 10 carcinoma. There were 11 patients in the surveillance group. Two first-order features in unenhanced CT and one in arterial CT, and 14 second-order parameters in unenhanced and venous CT and 10 second-order features in arterial CT, were able to differentiate adrenocortical carcinoma from adenoma (P < 0.050). After excluding two malignant outliers, the unsupervised machine learning approach correctly predicted malignancy in seven of eight adrenocortical carcinomas in all phases.

CONCLUSION: Radiomics with CT texture analysis was able to discriminate malignant from benign adrenocortical tumours, even by an unsupervised machine learning approach, in nearly all patients.

PMID:33677483 | PMC:PMC7937424 | DOI:10.1093/bjsopen/zraa061

Stereoisomeric selectivity in the endocrine-disrupting potential of cypermethrin using in vitro, in vivo, and in silico assays

Fetched: March 9th, 2021, 5:00am GMT by Quan Zhang

J Hazard Mater. 2021 Feb 20;414:125389. doi: 10.1016/j.jhazmat.2021.125389. Online ahead of print.

ABSTRACT

Despite the ubiquity of cypermethrin (CYP) stereoisomers in environment biota, the stereoisomeric selectivity of endocrine-disrupting potency of α-CYP, β-CYP, and θ-CYP has not been well studied. In this study, dual-luciferase reporter gene assays were adopted to analyze their potential endocrine-disrupting effects via four receptors (ERα, GRα, MR and RXR). The results showed that α-CYP was antagonistic to ERα, GRα, and MR with RIC20 of 9.1 × 10^-7, 7.6 × 10^-7, and 1.0 × 10^-6 M, respectively. β-CYP exhibited only ERα-mediated agonistic activity with a REC20 of 2.1 × 10^-6 M. None of the CYP stereoisomers interacted with RXR. Molecular docking indicated that α-CYP had the strongest binding capacity to GRα among the compounds. The expression levels of steroid hormone-related genes in human adrenocortical carcinoma (H295R) cells displayed that all three compounds inhibited the transcription of 3-βHSD, indicating the block of turning cholesterol into different hormones. Both α-CYP and β-CYP upregulated genes encoding estrogen- and aldosterone-forming enzymes including 17-βHSD, CYP19, STAR, and CYP11B2. Mortality and malformation toxicity assays in zebrafish embryos revealed that the order of toxicity was α-CYP > β-CYP > θ-CYP. Our results indicated that α-CYP may pose the strongest endocrine-disrupting effects. The data provided here will be helpful to systematically understand stereoisomeric selectivity in the endocrine-disrupting effects of cypermethrin.

PMID:33677314 | DOI:10.1016/j.jhazmat.2021.125389

Permalink for 'A rare association of two endocrine tumours: non-functional oncocytic adrenocortical carcinoma and Papillary thyroid carcinoma'

A rare association of two endocrine tumours: non-functional oncocytic adrenocortical carcinoma and Papillary thyroid carcinoma

Fetched: March 7th, 2021, 5:00am GMT by Jorge Gabriel Ruiz-Sánchez

Horm Mol Biol Clin Investig. 2021 Mar 8. doi: 10.1515/hmbci-2020-0080. Online ahead of print.

ABSTRACT

OBJECTIVES: To describe a rare association of two endocrine tumours in a clinical case.

CASE PRESENTATION: A 54-year-old woman with a classic Papillary thyroid cancer (PTC) assessed by the Endocrinology Department of a tertiary hospital from May-2015 to May-2020. PTC was treated with a total thyroidectomy and lymphadenectomy in May-2015. Initial staging (AJCC/TNM 7th edition): T3N1bMx. Additionally, two ablative doses of 150 mCi of 131-I (RAI) were administered until September-2016. No pathological uptake was found on the post-RAI whole-body scan at any level. Due to a persistent incomplete biochemical response in February-2017, a ¹⁸Fluor-dexosiglucose positron emission computed tomography (FDG-PET) was performed. FDG-PET showed an intense pathological deposit in the right adrenal, suggestive of malignancy. Right adrenalectomy was carried out, and pathology revealed an Adrenocortical carcinoma (ACC). Genetic syndromes associated to ACC are: Li-Fraumeni syndrome (caused by an autosomal mutation in the TP53 gene), the Multiple Endocrine Neoplasia (MEN) type 1 (caused by Menin gene mutations), and MEN type 4 (caused by heterozygous mutations in the CDNK1B gene). However, none of them are associated to PTC.

CONCLUSIONS: To our knowledge this is the sixth published case reporting an ACC in presence of a PTC. The pathological factors behind the relation between these malignancies have not been elucidated. We do not discard the possibility of a genetic relationship between PTC and ACC.

PMID:33675218 | DOI:10.1515/hmbci-2020-0080

Permalink for 'Identification of NDRG Family Member 4 (NDRG4) and CDC28 Protein Kinase Regulatory Subunit 2 (CKS2) as Key Prognostic Genes in Adrenocortical Carcinoma by Transcriptomic Analysis'

Identification of NDRG Family Member 4 (NDRG4) and CDC28 Protein Kinase Regulatory Subunit 2 (CKS2) as Key Prognostic Genes in Adrenocortical Carcinoma by Transcriptomic Analysis

Fetched: March 6th, 2021, 5:00am GMT by Zhengqing Yang

Med Sci Monit. 2021 Mar 5;27:e928523. doi: 10.12659/MSM.928523.

ABSTRACT

BACKGROUND Adrenocortical carcinoma (ACC) is an aggressive cancer with heterogeneous outcomes. In this study, we aimed to investigate genomic and prognostic features of ACC. MATERIAL AND METHODS Clinical, pathologic, and transcriptomic data from 2 independent datasets derived from ACC samples (TCGA-ACC dataset, GEO-GSE76021 dataset) were collected. Weighted gene co-expression network analysis (WGCNA) and survival analyses were performed to identify prognostic genes. Pathway analysis was performed for mechanistic analysis. xCell deconvolution was performed for tumor microenvironment analysis. RESULTS In the TCGA-ACC cohort, WGCNA identified a prognostic module of 5408 genes. Differential expression analysis identified 1969 genes that differed in expression level between long-term and short-term survivors. Univariate Cox regression model analysis identified 8393 genes with prognostic value. The intersection of these gene sets included 820 prognostic genes. Similar protocols were performed for the GSE76021 dataset, and 5 candidate genes were identified. Further intersection of these genes finally identified NDRG4 and CKS2 as key prognostic genes. Multivariate Cox regression model analysis validated the prognostic value of NDRG4 (HR=0.61, 95% CI 0.46-0.80) and CKS2 (HR=2.52, 95% CI 1.38-4.60). Moreover, NDRG4 and CKS2 expression predicted survival in patients treated with mitotane (P<0.001). Further mechanism exploration found an association between CKS2 and DNA mismatch repair pathways. Moreover, NDRG4 positively correlated with CD8⁺ T cell infiltration, while CKS2 negatively correlated with it. CONCLUSIONS We identified NDRG4 and CKS2 expression as key prognostic genes in ACC, which may help in risk stratification of ACC. Moreover, a close relationship was found between CKS2 and mismatch repair pathways. Moreover, immune cell infiltration differed according to NDRG4 and CKS2 expression.

PMID:33667214 | PMC:PMC7941762 | DOI:10.12659/MSM.928523

Rare but serious cause for hypokalaemia and hypertension

Fetched: March 6th, 2021, 5:00am GMT by Hussun-Ara Shah

BMJ Case Rep. 2021 Mar 4;14(3):e239955. doi: 10.1136/bcr-2020-239955.

ABSTRACT

Adrenocortical carcinoma is a rare tumour but hypertension conversely is very common. We present the case of a woman in her 30s, with poorly controlled hypertension on four antihypertensive agents. She was referred to the accident and emergency department with hypokalaemia. For a year, she had experienced oedema, weight gain, acne, hirsutism and oligomenorrhea. She had a classic Cushingoid appearance and marked striae. Cushing's syndrome was confirmed biochemically with an abnormal overnight dexamethasone suppression test. She was diagnosed with metastatic adrenocortical carcinoma following CT imaging. This was resected via a right adrenalectomy, nephrectomy and cholecystectomy. She also received mitotane. Unfortunately, she has a terminal prognosis having experienced a recurrence. This case demonstrates the value of a thorough clinical assessment. More importantly, it highlights the need to refer earlier patients under 40 with resistant hypertension to a specialist. Finally, it encourages clinicians to investigate hypokalaemia in the context of hypertension.

PMID:33664034 | PMC:PMC7934740 | DOI:10.1136/bcr-2020-239955

A case of adrenocortical adenoma harboring venous thrombus mimicking adrenal malignancy

Fetched: March 5th, 2021, 5:00am GMT by Agena Suzuki

Endocr J. 2021 Mar 4. doi: 10.1507/endocrj.EJ20-0667. Online ahead of print.

ABSTRACT

Advances in imaging technology and its widespread use have increased the number of identified patients with bilateral adrenal incidentalomas. The pathology of bilateral adrenal incidentalomas is gradually elucidated by its increased frequency. Although there is no consensus regarding the optimal management of bilateral adrenal lesions, adrenal lesions that are a suspected adrenocortical carcinoma on the basis of radiological imaging require surgical resection. We report a clinically interesting case of a 59-year-old female with adrenocortical adenoma harboring venous thrombus that mimicked adrenal malignancy. She was referred for evaluation of asymptomatic asymmetric lesions on both adrenal glands. Abdominal computed tomography and magnetic resonance imaging showed a 4.7-cm-diameter heterogenous lesion with peripheral enhancement in the right adrenal gland and a 2.0-cm-diameter homogenous lesion in the left adrenal gland. Adrenal scintigraphy with ¹³¹I-adosterol exhibited marked accumulation in the left lesion and slight accumulation in the middle inferior portion of the right lesion. Endocrine data revealed subclinical Cushing syndrome, and the patient underwent right laparoscopic adrenalectomy. The serum cortisol level was not suppressed on an overnight dexamethasone suppression test after the adrenalectomy. The resected tumor revealed a cortisol-producing adrenocortical adenoma harboring an organized and re-canalized venous thrombus, which was associated with focal papillary endothelial hyperplasia. This case illustrates the difficulty with preoperatively diagnosing this heterogeneously enhanced large benign adrenal lesion and differentiating it from adrenocortical carcinoma or angiosarcoma.

PMID:33658437 | DOI:10.1507/endocrj.EJ20-0667

Permalink for 'MYELOLIPOMA COEXISTENCE WITH GLUCOCORTICOID AND ANDROGEN SECRETING ADRENOCORTICAL CARCINOMA: SLOW AND BENIGN CLINICAL COURSE'

MYELOLIPOMA COEXISTENCE WITH GLUCOCORTICOID AND ANDROGEN SECRETING ADRENOCORTICAL CARCINOMA: SLOW AND BENIGN CLINICAL COURSE

Fetched: March 5th, 2021, 5:00am GMT by Taner Demirci

Georgian Med News. 2021 Jan;(310):7-11.

ABSTRACT

We present a case of androgen and glucocorticoid secreting adrenocortical carcinoma with concomitant myelolipoma. A giant adrenal tumor which was initially nonfunctional was reassessed four years later due to the patient's refusal to treat. The patient was a 48-year-old woman with hypertension and acne lesions on the face. Laboratory findings were consistent with glucocorticoid and androgen hypersecretion. Computed tomography revealed a heterogeneously contrasting mass of 145x118x100 mm with lobular contour and soft tissue areas. The patient underwent left laparoscopic transperitoneal adrenalectomy with three port technique. There were no complications in the perioperative period. The resected specimen weighed 850 grams. Pathological findings showed a combination of myelolipoma-adrenal cortical cancer. In the postoperative period, hypertension improved and the hormone panel was normalized. Postoperative computed tomography and PET-CT showed no residual mass and metastasis. Although imaging is compatible with benign masses such as myelolipoma, coexistence of ACC-myelolipoma should be kept in mind and functional evaluation should be performed.

PMID:33658401

Revisiting Cushing's Syndrome, Milder Forms Are Now a Common Occurrence- A Single Center Cohort of 76 Subjects

Fetched: March 3rd, 2021, 5:00am GMT by Arza Rosset

Endocr Pract. 2021 Feb 27:S1530-891X(21)00056-2. doi: 10.1016/j.eprac.2021.02.012. Online ahead of print.

ABSTRACT

OBJECTIVE: Guidelines recommend initiating testing for Cushing's syndrome (CS) on the basis of a "strong clinical suspicion". Our experience suggests classical stigmata are absent in the majority of patients with CS diagnosed in recent years. We aimed to confirm this premise by revisiting the clinical features of this syndrome in a modern series of patients from one center.

METHODS: Computerized records of subjects with CS diagnosed at Tel Aviv-Sourasky Medical Center between 2000-2018 were reviewed. A Cushing's inventory score (CIS), including all clinical components of the syndrome, was computed for each subject. Data were compared between the subtypes, and evaluated in light of those in the literature.

RESULTS: Of the 76 subjects with CS (60 women/16 men), 49 had Cushing's disease (64.5%), 16 had an adrenal adenoma (21.1%), 7 an adrenocortical carcinoma (9.2%), and 4 had ectopic ACTH secretion (5.3%). In only 20.3% a clinical suspicion of CS led to testing. Catabolic signs of CS were present in less than 30% of cases. The most common symptom was weight gain (77.6%), and the most common comorbidity was hypertension (61.8%). There were no differences in CIS between the subtypes. Signs, symptoms, and comorbidities were all significantly less common than in the classical syndrome.

CONCLUSIONS: - Modern CS presents with subtler features than in the past. Initiating a testing cascade solely on the basis of a strong clinical suspicion may lead to underdiagnosis of milder cases. A concerted effort to devise cost-efficient testing for CS in the current era is needed.

PMID:33652108 | DOI:10.1016/j.eprac.2021.02.012

Construction of a robust prognostic model for adult adrenocortical carcinoma: Results from bioinformatics and real-world data

Fetched: February 25th, 2021, 5:00am GMT by Xi Tian

J Cell Mol Med. 2021 Apr;25(8):3898-3911. doi: 10.1111/jcmm.16323. Epub 2021 Feb 24.

ABSTRACT

This study aims to construct a robust prognostic model for adult adrenocortical carcinoma (ACC) by large-scale multiomics analysis and real-world data. The RPPA data, gene expression profiles and clinical information of adult ACC patients were obtained from The Cancer Proteome Atlas (TCPA), Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Integrated prognosis-related proteins (IPRPs) model was constructed. Immunohistochemistry was used to validate the prognostic value of the IPRPs model in Fudan University Shanghai Cancer Center (FUSCC) cohort. 76 ACC cases from TCGA and 22 ACC cases from GSE10927 in NCBI's GEO database with full data for clinical information and gene expression were utilized to validate the effectiveness of the IPRPs model. Higher FASN (P = .039), FIBRONECTIN (P < .001), TFRC (P < .001), TSC1 (P < .001) expression indicated significantly worse overall survival for adult ACC patients. Risk assessment suggested significantly a strong predictive capacity of IPRPs model for poor overall survival (P < .05). IPRPs model showed a little stronger ability for predicting prognosis than Ki-67 protein in FUSCC cohort (P = .003, HR = 3.947; P = .005, HR = 3.787). In external validation of IPRPs model using gene expression data, IPRPs model showed strong ability for predicting prognosis in TCGA cohort (P = .005, HR = 3.061) and it exhibited best ability for predicting prognosis in GSE10927 cohort (P = .0898, HR = 2.318). This research constructed IPRPs model for predicting adult ACC patients' prognosis using proteomic data, gene expression data and real-world data and this prognostic model showed stronger predictive value than other biomarkers (Ki-67, Beta-catenin, etc) in multi-cohorts.

PMID:33626208 | PMC:PMC8051734 | DOI:10.1111/jcmm.16323

Cushing's syndrome and bone metastases as the manifestation of adrenocortical carcinoma

Fetched: February 25th, 2021, 5:00am GMT by Anna Brona

Pol Arch Intern Med. 2021 Feb 24. doi: 10.20452/pamw.15829. Online ahead of print.

NO ABSTRACT

PMID:33624953 | DOI:10.20452/pamw.15829

Case report of adrenocortical carcinoma associated with double germline mutations in MSH2 and RET

Fetched: February 24th, 2021, 5:00am GMT by Margarita Raygada

Am J Med Genet A. 2021 Apr;185(4):1282-1287. doi: 10.1002/ajmg.a.62099. Epub 2021 Feb 21.

ABSTRACT

Adrenocortical carcinoma (ACC) is a rare aggressive malignancy that originates in the outer layer of the adrenal gland. Most ACCs are sporadic, but a small percentage of cases are due to hereditary cancer syndromes such as Li-Fraumeni syndrome (LFS), Lynch syndrome (LS), and familial adenomatous polyposis (FAP). Multiple endocrine neoplasia type 2A (MEN2A) is an inherited disorder that predisposes to medullary thyroid cancer, pheochromocytoma, and parathyroid hyperplasia. We present here a case of ACC with both LS and MEN2A; the family and medical history were consistent with Lynch. This is, to our knowledge, the first report of a patient with ACC associated with germline mutations in RET and MSH2, and no phenotypical characteristics of MEN2A.

PMID:33615670 | PMC:PMC7986073 | DOI:10.1002/ajmg.a.62099

Rare Cancers of Childhood Treatment (PDQ®): Patient Version

Fetched: February 24th, 2021, 5:00am GMT by PDQ Pediatric Treatment Editorial Board

2021 Feb 18. In: PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002–.

ABSTRACT

This PDQ cancer information summary has current information about the treatment of rare cancers of childhood. It is meant to inform and help patients, families, and caregivers. It does not give formal guidelines or recommendations for making decisions about health care.

Editorial Boards write the PDQ cancer information summaries and keep them up to date. These Boards are made up of experts in cancer treatment and other specialties related to cancer. The summaries are reviewed regularly and changes are made when there is new information. The date on each summary ("Date Last Modified") is the date of the most recent change. The information in this patient summary was taken from the health professional version, which is reviewed regularly and updated as needed, by the PDQ Pediatric Treatment Editorial Board.

PMID:26389276 | Bookshelf:NBK65835

Germline TP53 Testing in Breast Cancers: Why, When and How?

Fetched: February 24th, 2021, 5:00am GMT by D Gareth Evans

Cancers (Basel). 2020 Dec 14;12(12):3762. doi: 10.3390/cancers12123762.

ABSTRACT

Germline TP53 variants represent a main genetic cause of breast cancers before 31 years of age. Development of cancer multi-gene panels has resulted in an exponential increase of germline TP53 testing in breast cancer patients. Interpretation of TP53 variants, which are mostly missense, is complex and requires excluding clonal haematopoiesis and circulating tumour DNA. In breast cancer patients harbouring germline disease-causing TP53 variants, radiotherapy contributing to the development of subsequent tumours should be, if possible, avoided and, within families, annual follow-up including whole-body MRI should be offered to carriers. We consider that, in breast cancer patients, germline TP53 testing should be performed before treatment and offered systematically only to patients with: (i) invasive breast carcinoma or ductal carcinoma in situ (DCIS) before 31; or (ii) bilateral or multifocal or HER2+ invasive breast carcinoma/DCIS or phyllode tumour before 36; or (iii) invasive breast carcinoma before 46 and another TP53 core tumour (breast cancer, soft-tissue sarcoma, osteosarcoma, central nervous system tumour, adrenocortical carcinoma); or (iv) invasive breast carcinoma before 46 and one first- or second-degree relative with a TP53 core tumour before 56. In contrast, women presenting with breast cancer after 46, without suggestive personal or familial history, should not be tested for TP53.

PMID:33327514 | PMC:PMC7764913 | DOI:10.3390/cancers12123762

Germline EGFR variants are over-represented in adolescents and young adults (AYA) with adrenocortical carcinoma

Fetched: February 24th, 2021, 5:00am GMT by Sara Akhavanfard

Hum Mol Genet. 2021 Jan 21;29(22):3679-3690. doi: 10.1093/hmg/ddaa268.

ABSTRACT

Adrenocortical Carcinoma (ACC) is a rare endocrine tumor with poor overall prognosis and 1.5-fold overrepresentation in females. In children, ACC is associated with inherited cancer syndromes with 50-80% of childhood-ACC associated with TP53 germline variants. ACC in adolescents and young adults (AYA) is rarely due to germline TP53, IGF2, PRKAR1A and MEN1 variants. We analyzed exome sequencing data from 21 children (<15y), 32 AYA (15-39y), and 60 adults (>39y) with ACC, and retained all pathogenic, likely pathogenic, and highly prioritized variants of uncertain significance. We engineered a stable lentiviral-mutant ACC cell line, harboring an EGFR variant (p.Asp1080Asn) from a 21-year-old female without germline-TP53-variant and with aggressive ACC. We found that 4.8% of the children (P = 0.004) and 6.2% of AYA (P < 0.0001), all-female participants, harbored germline EGFR variants, compared to only 0.3% of the control group. Expanding our analysis to the RTK-RAS-MAPK pathway, we found that the RTK genes have the highest number of highly prioritized germline variants in these individuals amongst all three arms of this pathway. We showed EGFR mutant cells migrate faster and are characterized by a stem-like phenotype compared to wild type cells. While EGFR inhibitors did not affect the stemness of mutant cells, Sunitinib, a multireceptor tyrosine kinase inhibitor, significantly reduced their stem-like behavior. Our data suggest that EGFR could be a novel underlying germline predisposition factor for ACC, especially in the Childhood-AYA (C-AYA) population. Further clinical validation can improve precision oncology management of this disease, which is known to have limited therapeutic options.

PMID:33326033 | DOI:10.1093/hmg/ddaa268

Percutaneous transmyocardial ablation of a metastatic adrenocortical carcinoma invading the interventricular septum

Fetched: February 24th, 2021, 5:00am GMT by Xudong Xie

Eur Heart J. 2020 Dec 15:ehaa911. doi: 10.1093/eurheartj/ehaa911. Online ahead of print.

NO ABSTRACT

PMID:33320933 | DOI:10.1093/eurheartj/ehaa911

Clinical prognostic factors in pediatric adrenocortical tumors: A meta-analysis

Fetched: February 24th, 2021, 5:00am GMT by Elisa Zambaiti

Pediatr Blood Cancer. 2021 Mar;68(3):e28836. doi: 10.1002/pbc.28836. Epub 2020 Dec 11.

ABSTRACT

Pediatric adrenocortical tumors (ACT) are rare and sometimes aggressive malignancies, but there is no consensus on the outcome predictors in children. A systematic search of MEDLINE, SCOPUS, Web of Science, and the Cochrane Library for studies from 1994 to 2020 about pediatric ACT was performed. In 42 studies, 1006 patients, aged 0-18 years, were included. The meta-analyses resulted in the following predictors of better outcome: age <4 years (P < .00001), nonsecreting tumors (P = .004), complete surgical resection (P < .00001), tumor volume (P < .0001), tumor weight (P < .00001), tumor maximum diameter (P = .0009), and Stage I disease (P < .00001). Moreover, patients affected by Cushing syndrome showed a worse outcome (P < .0001). International prospective studies should be implemented to standardize clinical prognostic factors evaluation, together with pathological scores, in the stratification of pediatric ACT.

PMID:33306282 | DOI:10.1002/pbc.28836

Cystic adrenal lesions: A report of five cases

Fetched: February 24th, 2021, 5:00am GMT by Divya Goel

Cancer Rep (Hoboken). 2021 Feb;4(1):e1314. doi: 10.1002/cnr2.1314. Epub 2020 Dec 9.

ABSTRACT

BACKGROUND: Cystic adrenal lesions are rare and uncommon manifestation with few cases reported so far. Different types of adrenal cysts have been described with heterogeneous etiology and overlapping clinical findings, ranging from benign to malignant cystic neoplasm. They are usually asymptomatic or may rarely present with abdominal pain or fullness. Optimum management of adrenal cysts still remain controversial, owing to its low incidence. In this study, we report our institutional experience on diagnosis and management of different histological types of cystic adrenal lesions.

CASES: During 4 years period, 55 patients underwent adrenalectomy with five cases presenting as adrenal cysts. All the five patients were biochemically nonfunctional and underwent adrenalectomy (laparoscopic anterior n = 2, retroperitoneoscopic approach n = 1, and open anterior transperitoneal approach n = 2). The primary indications for surgery were larger size and/or suspicion of malignancy. Histological evaluation revealed two epithelial cysts, one endothelial cyst, one pseudocyst, and a very rare case of adrenocortical carcinoma arising in a pseudocyst.

CONCLUSION: Cystic adrenal lesions are rare with varied etiologic and clinical presentation that may sometimes lead to diagnostic and management dilemma. These cases must undergo biochemical and radiological evaluation to rule out underlying malignancy followed by referral for surgical intervention.

PMID:33295135 | DOI:10.1002/cnr2.1314

The diagnostic and prognostic values of microRNA-196a in cancer

Fetched: February 24th, 2021, 5:00am GMT by Mengqiu Xiong

Biosci Rep. 2021 Jan 29;41(1):BSR20203559. doi: 10.1042/BSR20203559.

ABSTRACT

MicroRNA-196a (miR-196a) was previously reported to be up-regulated in cancers, and it has the diagnostic and prognostic values in cancers. Whereas, the conclusion was still unclear according to the published data. To assess such roles of miR-196a in cancers, the present study was conducted based on published data and online cancer-related databases. To identify the relevant published data, we searched articles in databases and then the relevant data were extracted to evaluate the correlation between miR-196a expression and diagnosis, prognosis for cancer patients. The pooled results showed that miR-196a was a valuable diagnostic biomarker in cancer (area under curve (AUC) = 0.87, 95% CI: 0.84-0.90; sensitivity (SEN) = 0.73, 95% CI: 0.64-0.81; specificity (SPE) = 0.90, 95% CI: 0.81-0.95), which was consistent with the data from databases (breast cancer: miR-196a-3p: AUC = 0.77, 95% CI: 0.74-0.79; miR-196a-5p: AUC = 0.71, 95% CI: 0.66-0.75; pancreatic cancer: miR-196a-3p: AUC = 0.80, 95% CI: 0.73-0.87; miR-196a-5p: AUC = 0.61, 95% CI: 0.51-0.71). In addition, the pooled result revealed that elevated miR-196a expression in tumor tissues (HR = 2.54, 95% CI: 1.79-3.61, PHeterogeneity=0.000, I2 = 75.8%) or serum/plasma (HR = 4.06, 95% CI: 2.67-6.18, PHeterogeneity=0.668, I2 = 0%) of patients was an unfavorable survival biomarker, which was consistent with the data from databases (adrenocortical carcinoma: HR = 5.70; esophageal carcinoma: HR = 1.93; brain lower grade glioma: HR = 2.91; GSE40267: HR = 2.47, 95% CI: 1.2-5.07; TCGA: HR = 1.82, 95% CI: 1.21-2.74; GSE19783: HR = 4.24, 95% CI: 1-18.06). In short, our results demonstrated that miR-196a in tumor tissue or serum/plasma could be used as a prognostic and diagnostic values for cancers.

PMID:33289788 | PMC:PMC7791550 | DOI:10.1042/BSR20203559

Permalink for 'CTNNB1 Knockdown Inhibits Cell Proliferation and Aldosterone Secretion Through Inhibiting Wnt/β-Catenin Signaling in H295R Cells'

CTNNB1 Knockdown Inhibits Cell Proliferation and Aldosterone Secretion Through Inhibiting Wnt/β-Catenin Signaling in H295R Cells

Fetched: February 24th, 2021, 5:00am GMT by Tingting Zhou

Technol Cancer Res Treat. 2020 Jan-Dec;19:1533033820979685. doi: 10.1177/1533033820979685.

ABSTRACT

Aldosterone-producing adenomas (APA) is one of the causative factors of primary aldosteronism. Previous studies have suggested that there are somatic CTNNB1 mutations in APA, but the specific mechanism of CTNNB1 mutation in APA tumorigenesis and aldosterone secretion remains unclear. In the present study, human adrenocortical carcinoma cell line H295 R was used to establish stable CTNNB1 knockdown cell lines. Cell proliferation and aldosterone secretion of H295 R cells in response to angiotensin Ⅱ (Agn Ⅱ) were analyzed. We found that CTNNB1 knockdown reduced β-catenin expression and inhibited proliferation of H295 R cells. CTNNB1 knockdown inhibited Wnt/β-catenin signaling pathway and downregulated expression of downstream genes including axin 2, lymphoid enhancer binding factor 1 (LEF1), and cyclin D1. In addition, CTNNB1 knockdown decreased responses of H295 R cells to Agn Ⅱ and decreased aldosterone secretion. Our findings suggest that CTNNB1 knockdown can inhibit H295 R cell proliferation and decrease aldosterone secretion in the responses of H295 R cells to Ang II through inhibiting Wnt/β-catenin signaling pathway, indicating that targeting Wnt/β-catenin signaling pathway may be an important approach to decrease aldosterone secretion in the treatment of aldoster-producing adenomas.

PMID:33287648 | PMC:PMC7727057 | DOI:10.1177/1533033820979685

Permalink for 'A Pan-Cancer Study of Somatic TERT Promoter Mutations and Amplification in 30,773 Tumors Profiled by Clinical Genomic Sequencing'

A Pan-Cancer Study of Somatic TERT Promoter Mutations and Amplification in 30,773 Tumors Profiled by Clinical Genomic Sequencing

Fetched: February 24th, 2021, 5:00am GMT by Sounak Gupta

J Mol Diagn. 2021 Feb;23(2):253-263. doi: 10.1016/j.jmoldx.2020.11.003. Epub 2020 Dec 5.

ABSTRACT

TERT gene promoter mutations are known in multiple cancer types. Other TERT alterations remain poorly characterized. Sequencing data from 30,773 tumors analyzed by a hybridization capture next-generation sequencing assay (Memorial Sloan Kettering Cancer Center Integrated Mutation Profiling of Actionable Cancer Targets) were analyzed for the presence of TERT alterations. Promoter rearrangements (500 bases upstream of the transcriptional start site), hypermethylation (n = 57), and gene expression (n = 155) were evaluated for a subset of cases. Mutually exclusive and recurrent promoter mutations were identified at three hot spots upstream of the transcriptional start site in 11.3% of cases (-124: 74%; -146: 24%; and -138: <2%). Mutually exclusive amplification events were identified in another 2.3% of cases, whereas mutually exclusive rearrangements proximal to the TERT gene were seen in 24 cases. The highest incidence of TERT promoter mutations was seen in cutaneous melanoma (82%), whereas amplification events significantly outnumbered promoter mutations in well-differentiated/dedifferentiated liposarcoma (14.1% versus 2.4%) and adrenocortical carcinoma (13.6% versus 4.5%). Gene expression analysis suggests that the highest levels of gene expression are seen in cases with amplifications and rearrangements. Hypermethylation events upstream of the TERT coding sequence were not mutually exclusive with known pathogenic alterations. Studies aimed at defining the prevalence and prognostic impact of TERT alterations should incorporate other pathogenic TERT alterations as these may impact telomerase function.

PMID:33285287 | PMC:PMC7874333 | DOI:10.1016/j.jmoldx.2020.11.003

A case of adrenocortical oncocytic carcinoma arising in ectopic adrenal tissue: a multidisciplinary diagnostic challenge

Fetched: February 24th, 2021, 5:00am GMT by Nikita Wadhwani

Ecancermedicalscience. 2020 Nov 5;14:1135. doi: 10.3332/ecancer.2020.1135. eCollection 2020.

ABSTRACT

Adrenocortical oncocytic neoplasm arising in ectopic adrenal tissue is a rare finding and presents as a unique diagnostic challenge. We report a case of a 26-year-old female who presented with vague left-sided abdominal pain and a large left retroperitoneal mass. She underwent exploratory laparotomy and resection of the mass and was diagnosed with extra-adrenal adrenocortical oncocytic carcinoma.

PMID:33281927 | PMC:PMC7685763 | DOI:10.3332/ecancer.2020.1135

Yttrium-90 radioembolization of isolated hepatic adrenocortical carcinoma metastases with negative surgical pathology.

Fetched: February 21st, 2021, 5:00am GMT

EJNMMI Res. 2021 Feb 18;11(1):17. doi: 10.1186/s13550-021-00755-0.

ABSTRACT

BACKGROUND: Adrenocortical carcinoma (ACC) is an uncommon malignancy with an estimated 15,400 new cases annually across the globe. The prognosis is generally poor as the disease is often already advanced at initial diagnosis due to non-specific symptoms. Even for local disease, recurrence after surgical resection is high. Treatment choices for advanced disease include mitotane, chemotherapy, ablation, chemoembolization, radioembolization, and external beam radiotherapy, with varying degrees of efficacy. To the best of our knowledge, there have only been two prior case studies of complete clinical and radiological response of stage 4 disease at 1 year and 2 years after yttrium-90 (⁹⁰Y) microsphere selective internal radiation therapy (SIRT) of isolated hepatic metastases post-surgery and chemotherapy.

CASE PRESENTATION: We present a case of a 58-year-old man with metastatic ACC who was treated with ⁹⁰Y resin microsphere (SIR-spheres) for local control of liver metastases leading to a surgically proven negative pathology after partial hepatectomy 7 months after SIRT. The patient was initially diagnosed with stage 1 ACC that progressed 6 years later to stage 4 disease with new liver metastases that were deemed unresectable at an outside institution. After review of the case at multidisciplinary tumor board, he was referred for liver directed therapy for local tumor control. Angiographic workup demonstrated partial extrahepatic supply to the tumors from the right inferior phrenic artery, which was successfully embolized on the day of SIRT for flow redistribution. As the patient was being treated with mitotane that suppresses steroid production, he developed post-SIRT adrenal crisis, which was successfully controlled with steroids, highlighting the need for pre SIRT stress dose steroids.

CONCLUSIONS: This case continues to add to the literature supporting ⁹⁰Y radioembolization as an effective treatment for isolated hepatic ACC metastases. Our case is the first to demonstrate surgically proven negative pathology after radioembolization. Further prospective study is warranted to better establish efficacy as well as safety of SIRT for ACC liver metastases.

PMID:33604708 | PMC:PMC7892660 | DOI:10.1186/s13550-021-00755-0

Adrenocortical Carcinoma in Eight Children: A Report and Literature Review.

Fetched: February 21st, 2021, 5:00am GMT

Cancer Manag Res. 2021 Feb 11;13:1307-1314. doi: 10.2147/CMAR.S289191. eCollection 2021.

ABSTRACT

OBJECTIVE: This study aimed to summarize the clinical characteristics, comprehensive treatment, and prognosis of adrenocortical carcinoma (ACC) in children.

METHODS: The clinical data of eight children with definite diagnoses of ACC were retrospectively analyzed, and statistical methods were used to analyze the clinical characteristics, comprehensive treatment mode, and prognosis of these patients.

RESULTS: (1) Clinical characteristics: two were males and six were females with the median age of onset was six-years old were involved. Four patients had a rash and precocious puberty as the symptoms of onset. European Network for the Study of Adrenal Tumors (ENSAT) staging: stage II, two patients; stage IV, six patients. (2) Comprehensive treatment: all eight patients underwent surgical treatment and received six cycles of chemotherapy: the regimen was "etoposide + pirarubicin + cisplatin + mitotane." (3) Prognosis analysis: among these eight patients, two patients died, two patients achieved complete remission, the disease was stable in four patients, and the overall five-year survival rate was 75%. Prognosis analyzed according to ENSAT staging (stage II versus stage IV) revealed that two-year survival rates of the two groups were 100% versus 65%, respectively, without statistical significant (χ ² = 1.066, P = 0.302). Prognosis analyzed according to Weiss score (Weiss score was <6, five patients;≥6, three patients) revealed That survival time of the two groups was 50±9.52 months versus 6±1.70 months, the two-year survival rates of the two groups were 100% versus 35%, and the difference in survival rates between these two groups was statistically significant (χ² = 4.091, P = 0.043).

CONCLUSION: The Weiss score is an important prognostic factor for ACC. The chemotherapy regimen "mitotane + etoposide + adriamycin + cisplatin" is recommended.

PMID:33603476 | PMC:PMC7884932 | DOI:10.2147/CMAR.S289191

[Hyperaldosteronism].

Fetched: February 21st, 2021, 5:00am GMT

Internist (Berl). 2021 Mar;62(3):245-251. doi: 10.1007/s00108-021-00972-8. Epub 2021 Feb 18.

ABSTRACT

Aldosterone is produced in the adrenal cortex and governs volume and electrolyte homeostasis. Hyperaldosteronism can occur either as primary aldosteronism (renin-independent) or secondary aldosteronism (renin-dependent). As the commonest cause of secondary hypertension, primary aldosteronism is associated with increased cardiovascular risk. Its most prevalent subtypes are aldosterone-producing adenomas as the most frequent unilateral form and bilateral hyperaldosteronism. Unilateral hyperplasia, familial hyperaldosteronism and aldosterone-producing carcinoma are rare. The aldosterone/renin ratio serves as a screening parameter for primary aldosteronism. If this ratio is elevated, confirmatory testing and adrenal imaging are performed. Adrenal venous sampling is considered the gold standard for the distinction of unilateral from bilateral disease. Unilateral disease can potentially be cured by adrenalectomy, whereas patients that are not candidates for surgery or have bilateral disease are treated with mineralocorticoid receptor antagonists. Over the past 10 years, somatic mutations in ion channels or transporters have been identified as causes of aldosterone-producing adenomas and so-called aldosterone-producing cell clusters (potential precursors of adenomas and correlates of bilateral hyperplasia, but also of subclinical hyperaldosteronism). In addition, germline mutations in overlapping genes cause familial hyperaldosteronism. Secondary hyperaldosteronism can occur in patients with hypertension treated with diuretics or in renal artery stenosis.

PMID:33599784 | DOI:10.1007/s00108-021-00972-8

IL-13Rα2 gene expression is a biomarker of adverse outcome in patients with adrenocortical carcinoma.

Fetched: February 18th, 2021, 5:00am GMT

PLoS One. 2021 Feb 16;16(2):e0246632. doi: 10.1371/journal.pone.0246632. eCollection 2021.

ABSTRACT

Adrenocortical carcinoma (ACC) is a rare but aggressive endocrine malignancy that usually results in a fatal outcome. To allow the better clinical management and reduce mortality, we searched for clinical and molecular markers that are reliable predictor of disease severity and clinical outcome in ACC patients. We determined a correlation between the overexpression of IL-13Rα2 and the clinical outcome in ACC patients using comprehensive data available in The Cancer Genome Atlas (TCGA) database. The dataset of 79 ACC subjects were divided into groups of low, medium, or high expression of IL-13Rα2 as determined by RNA-seq. These patients were also stratified by length of survival, overall survival, incidence of a new tumor event, incidence of metastasis, and production of excess hormones. We report a correlation between IL-13Rα2 expression and survival of subjects with ACC. High expression of IL-13Rα2 in ACC tumors was significantly associated with a lower patient survival rate and period of survival compared to low expression (p = 0.0084). In addition, high IL-13Rα2 expression was significantly associated with a higher incidence of new tumor events and excess hormone production compared to low or medium IL-13Rα2 expression. Within the cohort of patients that produced excess hormone, elevated IL-13Rα2 expression was significantly associated with a lower survival rate. Additionally, IL-13Rα1 had a potential relationship between transcript level and ACC survival. Our results and promising antitumor activity in preclinical models and trials indicate that IL-13Rα2 expression is an important prognostic biomarker of ACC disease outcome and a promising target for therapeutic treatment of ACC.

PMID:33591997 | PMC:PMC7886164 | DOI:10.1371/journal.pone.0246632

PDQ Cancer Information Summaries

Fetched: February 18th, 2021, 5:00am GMT

2021 Feb 10. In: PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002–.

ABSTRACT

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of rare cancers of childhood. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

PMID:26389315 | Bookshelf:NBK65876

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