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Adrenal Gland Cancer (338 unread)

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

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

Condition: Adrenocortical Carcinoma
Intervention: Drug: Pembrolizumab / Lenvatinib
Sponsor: National Cancer Center, Korea
Not yet recruiting

The Immune Reaction Upon COVID-19 Vaccination in the Belgian Cancer Population.

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

Condition: Cancer
Intervention: Other: Blood sampling
Sponsors: University Hospital, Antwerp; KomOpTegenKanker (non-profit organization)
Recruiting

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

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

Condition: Colorectal Cancer Metastatic
Interventions: Behavioral: Hypnosis; Behavioral: CBT
Sponsor: Institut du Cancer de Montpellier - Val d'Aurelle
Not yet 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

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 'Testing the Addition of an Anticancer Drug, Olaparib, to the Usual Chemotherapy (Temozolomide) for Advanced Neuroendocrine Cancer'

Testing the Addition of an Anticancer Drug, Olaparib, to the Usual Chemotherapy (Temozolomide) for Advanced Neuroendocrine Cancer

Posted: May 20th, 2020, 2:00pm GMT

Conditions: Advanced Adrenal Gland Pheochromocytoma; Advanced Paraganglioma; Metastatic Adrenal Gland Pheochromocytoma; Metastatic Paraganglioma; Unresectable Adrenal Gland Pheochromocytoma; Unresectable Paraganglioma
Interventions: Drug: Olaparib; Other: Quality-of-Life Assessment; Drug: Temozolomide
Sponsor: National Cancer Institute (NCI)
Recruiting

Permalink for 'Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial'

Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial

Posted: February 26th, 2020, 3:00pm GMT

Conditions: Recurrent Adrenal Gland Pheochromocytoma; Recurrent Ectomesenchymoma; Recurrent Ependymoma; Recurrent Ewing Sarcoma; Recurrent Hepatoblastoma; Recurrent Kidney Wilms Tumor; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Medulloblastoma; Recurrent Melanoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdoid Tumor of the Kidney; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Recurrent Thyroid Gland Carcinoma; Recurrent WHO Grade II Glioma; Refractory Adrenal Gland Pheochromocytoma; Refractory Ependymoma; Refractory Ewing Sarcoma; Refractory Hepatoblastoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Medulloblastoma; Refractory Melanoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Rhabdoid Tumor of the Kidney; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma; Refractory Thyroid Gland Carcinoma; Refractory WHO Grade II Glioma
Intervention: Drug: Tipifarnib
Sponsor: National Cancer Institute (NCI)
Recruiting

Paravertebral Block Versus Thoracic Epidural Analgesia

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

Conditions: Lung Cancer; Postoperative Pain
Interventions: Drug: Thoracic epidural; Drug: Paravertebral block
Sponsor: St. Olavs Hospital
Recruiting

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

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

Condition: Metastatic Tumors
Interventions: Radiation: palliative radiotherapy; Radiation: Stereotactic ablative radiotherapy
Sponsors: British Columbia Cancer Agency; London Regional Cancer Program, Canada; The Alfred; Beacon Hospital, Ireland; Edinburgh Cancer Center, Scotland; Metro South Hospital and Health Service via Princess Alexandra Hospital, Australia; Beatson West of Scotland Cancer Center; Cancer Trials Ireland
Recruiting

Permalink for 'Long-term Safety and Efficacy Extension Study for Participants With Advanced Tumors Who Are Currently on Treatment or in Follow-up in a Pembrolizumab (MK-3475) Study (MK-3475-587/KEYNOTE-587)'

Long-term Safety and Efficacy Extension Study for Participants With Advanced Tumors Who Are Currently on Treatment or in Follow-up in a Pembrolizumab (MK-3475) Study (MK-3475-587/KEYNOTE-587)

Posted: April 3rd, 2018, 2:00pm GMT

Condition: Solid Tumors
Interventions: Drug: Pembrolizumab; Drug: Standard of Care (SOC)
Sponsor: Merck Sharp & Dohme Corp.
Recruiting

Lu-177-DOTATATE (Lutathera) in Therapy of Inoperable Pheochromocytoma/ Paraganglioma

Posted: July 2nd, 2017, 2:00pm GMT

Conditions: Pheochromocytoma; Paraganglioma; Neuroendocrine Tumors; Neuroendocrine Neoplasms
Interventions: Drug: Lu-177-DOTATATE; Drug: Ga-68-DOTATATE; Drug: F-18-FDG; Drug: Amino Acid solution
Sponsor: National Cancer Institute (NCI)
Recruiting

Nivolumab and Ipilimumab in Treating Patients With Rare Tumors

Posted: July 15th, 2016, 2:00pm GMT

Conditions: Acinar Cell Carcinoma; Adenoid Cystic Carcinoma; Adrenal Cortex Carcinoma; Adrenal Gland Pheochromocytoma; Anal Canal Neuroendocrine Carcinoma; Anal Canal Undifferentiated Carcinoma; Angiosarcoma; Apocrine Neoplasm; Appendix Mucinous Adenocarcinoma; Bartholin Gland Transitional Cell Carcinoma; Basal Cell Carcinoma; Bladder Adenocarcinoma; Breast Metaplastic Carcinoma; Cervical Adenocarcinoma; Cholangiocarcinoma; Chordoma; Colorectal Squamous Cell Carcinoma; Desmoid Fibromatosis; Endometrial Transitional Cell Carcinoma; Endometrioid Adenocarcinoma; Esophageal Neuroendocrine Carcinoma; Esophageal Undifferentiated Carcinoma; Extrahepatic Bile Duct Carcinoma; Extramammary Paget Disease; Fallopian Tube Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Fibromyxoid Tumor; Gallbladder Carcinoma; Gastric Neuroendocrine Carcinoma; Gastric Squamous Cell Carcinoma; Gastric Undifferentiated Carcinoma; Gastrointestinal Stromal Tumor; Gestational Trophoblastic Tumor; Giant Cell Carcinoma; Human Papillomavirus-Independent Cervical Adenocarcinoma, Clear Cell-Type; Intestinal Neuroendocrine Carcinoma; Intrahepatic Cholangiocarcinoma; Lung Carcinoid Tumor; Lung Sarcomatoid Carcinoma; Major Salivary Gland Carcinoma; Malignant Odontogenic Neoplasm; Malignant Peripheral Nerve Sheath Tumor; Malignant Solid Neoplasm; Malignant Testicular Sex Cord-Stromal Tumor; Metastatic Malignant Neoplasm of Unknown Primary; Minimally Invasive Lung Adenocarcinoma; Mixed Mesodermal (Mullerian) Tumor; Mucinous Adenocarcinoma; Mucinous Cystadenocarcinoma; Nasal Cavity Adenocarcinoma; Nasal Cavity Carcinoma; Nasopharyngeal Carcinoma; Nasopharyngeal Papillary Adenocarcinoma; Nasopharyngeal Undifferentiated Carcinoma; Oral Cavity Carcinoma; Oropharyngeal Undifferentiated Carcinoma; Ovarian Adenocarcinoma; Ovarian Germ Cell Tumor; Ovarian Mucinous Adenocarcinoma; Ovarian Squamous Cell Carcinoma; Ovarian Transitional Cell Carcinoma; Pancreatic Acinar Cell Carcinoma; Pancreatic Neuroendocrine Carcinoma; Paraganglioma; Paranasal Sinus Adenocarcinoma; Paranasal Sinus Carcinoma; Parathyroid Gland Carcinoma; PEComa; Peritoneal Mesothelioma; Pituitary Gland Carcinoma; Placental Choriocarcinoma; Primary Peritoneal High Grade Serous Adenocarcinoma; Pseudomyxoma Peritonei; Rare Disorder; Scrotal Squamous Cell Carcinoma; Seminal Vesicle Adenocarcinoma; Seminoma; Serous Cystadenocarcinoma; Small Intestinal Adenocarcinoma; Small Intestinal Squamous Cell Carcinoma; Spindle Cell Neoplasm; Squamous Cell Carcinoma of the Penis; Teratoma With Somatic-Type Malignancy; Testicular Non-Seminomatous Germ Cell Tumor; Thyroid Gland Carcinoma; Tracheal Carcinoma; Transitional Cell Carcinoma; Ureter Adenocarcinoma; Ureter Squamous Cell Carcinoma; Urethral Adenocarcinoma; Urethral Squamous Cell Carcinoma; Vaginal Adenocarcinoma; Vaginal Squamous Cell Carcinoma, Not Otherwise Specified; Vulvar Carcinoma
Interventions: Procedure: Biospecimen Collection; Biological: Ipilimumab; Biological: Nivolumab
Sponsor: National Cancer Institute (NCI)
Recruiting

$Permalink for 'Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)'$

Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)

Posted: June 8th, 2015, 2:00pm GMT

Conditions: Advanced Malignant Solid Neoplasm; Bladder Carcinoma; Breast Carcinoma; Cervical Carcinoma; Colon Carcinoma; Colorectal Carcinoma; Endometrial Carcinoma; Esophageal Carcinoma; Gastric Carcinoma; Glioma; Head and Neck Carcinoma; Kidney Carcinoma; Liver and Intrahepatic Bile Duct Carcinoma; Lung Carcinoma; Lymphoma; Malignant Uterine Neoplasm; Melanoma; Ovarian Carcinoma; Pancreatic Carcinoma; Plasma Cell Myeloma; Prostate Carcinoma; Rectal Carcinoma; Recurrent Bladder Carcinoma; Recurrent Breast Carcinoma; Recurrent Cervical Carcinoma; Recurrent Colon Carcinoma; Recurrent Colorectal Carcinoma; Recurrent Esophageal Carcinoma; Recurrent Gastric Carcinoma; Recurrent Glioma; Recurrent Head and Neck Carcinoma; Recurrent Liver Carcinoma; Recurrent Lung Carcinoma; Recurrent Lymphoma; Recurrent Malignant Solid Neoplasm; Recurrent Melanoma; Recurrent Ovarian Carcinoma; Recurrent Pancreatic Carcinoma; Recurrent Plasma Cell Myeloma; Recurrent Prostate Carcinoma; Recurrent Rectal Carcinoma; Recurrent Skin Carcinoma; Recurrent Thyroid Gland Carcinoma; Recurrent Uterine Corpus Cancer; Refractory Lymphoma; Refractory Malignant Solid Neoplasm; Refractory Plasma Cell Myeloma; Skin Carcinoma; Thyroid Gland Carcinoma; Uterine Corpus Cancer
Interventions: Drug: Adavosertib; Drug: Afatinib; Drug: Afatinib Dimaleate; Drug: Binimetinib; Drug: Capivasertib; Drug: Copanlisib; Drug: Copanlisib Hydrochloride; Drug: Crizotinib; Other: Cytology Specimen Collection Procedure; Drug: Dabrafenib; Drug: Dabrafenib Mesylate; Drug: Dasatinib; Drug: Defactinib; Drug: Defactinib Hydrochloride; Drug: Erdafitinib; Drug: FGFR Inhibitor AZD4547; Drug: Ipatasertib; Other: Laboratory Biomarker Analysis; Drug: Larotrectinib; Drug: Larotrectinib Sulfate; Biological: Nivolumab; Drug: Osimertinib; Drug: Palbociclib; Biological: Pertuzumab; Drug: PI3K-beta Inhibitor GSK2636771; Biological: Relatlimab; Drug: Sapanisertib; Drug: Sunitinib Malate; Drug: Taselisib; Drug: Trametinib; Biological: Trastuzumab; Biological: Trastuzumab Emtansine; Drug: Ulixertinib; Drug: Vismodegib
Sponsor: National Cancer Institute (NCI)
Recruiting

A Phase IV Post Approval Clinical Study of ExAblate Treatment of Metastatic Bone Tumors for the Palliation of Pain

Posted: April 17th, 2013, 2:00pm GMT

Condition: Bone Metastasis
Intervention: Device: ExAblate MRgFUS
Sponsor: InSightec
Recruiting

An Investigation of Pituitary Tumors and Related Hypothalmic Disorders

Posted: November 4th, 1999, 3:00pm GMT

Conditions: Panhypopituitarism; Gigantism/Acromegaly; Prolactinoma; Cushing Disease
Intervention:
Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Recruiting

Robotic Surgery in Pediatric Oncology: Lessons Learned from the First 100 Tumors-A Nationwide Experience

Fetched: September 16th, 2021, 5:00am GMT by Thomas Blanc

Ann Surg Oncol. 2021 Sep 14. doi: 10.1245/s10434-021-10777-6. Online ahead of print.

ABSTRACT

BACKGROUND: While robotics has become commonplace in adult oncology, it remains rare in pediatric oncology due to the rarity of childhood cancers. We present the results of a large nationwide experience with robotic oncology, with the aim of providing practical and feasible guidelines for child selection.

METHODS: This was a prospective analysis performed over a period of 4 years. Treatment was delivered according to the Société Internationale d'Oncologie Pédiatrique/International Society of Paediatric Oncology Europe Neuroblastoma Group (SIOP/SIOPEN) protocols. Indications were approved by a certified tumor board.

RESULTS: Overall, 100 tumors were resected during 93 procedures (abdomen, 67%; thorax, 17%; pelvis, 10%; retroperitoneum, 6%) in 89 children (56 girls). The median age at surgery was 8.2 years (range 3.6-13); 19 children (21%) harbored germinal genetic alterations predisposing to cancer. No intraoperative tumor ruptures occurred. Seven conversions (8%) to an open approach were performed. Neuroblastic tumors (n = 31) comprised the main group (18 neuroblastomas, 4 ganglioneuroblastomas, 9 ganglioneuromas) and renal tumors comprised the second largest group (n = 24, including 20 Wilms' tumors). The remaining 45 tumors included neuroendocrine (n = 12), adrenal (n = 9), germ-cell (n = 7), pancreatic (n = 4), thymic (n = 4), inflammatory myofibroblastic (n = 4), and different rare tumors (n = 5). Overall, 51 tumors were malignant, 2 were borderline, and 47 were benign. The median hospital stay was 3 days (2-4), and five postoperative complications occurred within the first 30 days. During a median follow-up of 2.4 years, one child (Wilms' tumor) presented with pleural recurrence. One girl with Wilms' tumor died of central nervous system metastasis.

CONCLUSIONS: Robotic surgery for pediatric tumors is a safe option in highly selected cases. Indications should be discussed by tumor boards to avoid widespread and uncontrolled application.

PMID:34523002 | DOI:10.1245/s10434-021-10777-6

An Adrenocortical Carcinoma Evolving After Nine Years of Latency From a Small Adrenal Incidentaloma

Fetched: September 16th, 2021, 5:00am GMT by Harpreet S Kohli

Cureus. 2021 Aug 3;13(8):e16851. doi: 10.7759/cureus.16851. eCollection 2021 Aug.

ABSTRACT

Adrenal incidentalomas (AIs) are common incidental findings in medical practice with clinical significance. Although most AIs are nonsecretory and nonmalignant, they require a short course of follow-up over one to two years to rule out malignancy or hormonal secretion according to clinical practice guidelines. However, this can result in some adrenocortical carcinomas (ACCs) being missed if they transform at a later stage or evolve slowly. Here, we report one such case of an AI, which although remained indolent, eventually transformed into an ACC many years after the initial detection.

PMID:34522492 | PMC:PMC8425154 | DOI:10.7759/cureus.16851

Adrenal-permissive HSD3B1 genetic inheritance and risk of estrogen-driven postmenopausal breast cancer

Fetched: September 15th, 2021, 5:00am GMT by Megan L Kruse

JCI Insight. 2021 Sep 14:150403. doi: 10.1172/jci.insight.150403. Online ahead of print.

ABSTRACT

BACKGROUND: Genetics of estrogen synthesis and breast cancer risk has been elusive. The 1245A→C missense-encoding polymorphism in HSD3B1, which is common in White populations, is functionally adrenal permissive and increases synthesis of the aromatase substrate, androstenedione. We hypothesized that homozygous inheritance of the adrenal-permissive HSD3B1(1245C) is associated with postmenopausal estrogen receptor (ER)-positive breast cancer.

METHODS: A prospective study of postmenopausal ER-driven breast cancer was done for determination of HSD3B1 and circulating steroids. Validation was performed in 2 other cohorts. Adrenal-permissive genotype frequency was compared between postmenopausal ER-positive breast cancer, the general population, and postmenopausal ER-negative breast cancer.

RESULTS: Prospective and validation studies had 157 and 538 subjects, respectively, for the primary analysis of genotype frequency by estrogen receptor status in White female breast cancer patients postmenopausal at diagnosis. The adrenal-permissive genotype frequency in postmenopausal White women with estrogen-driven breast cancer in the prospective cohort was 17.5% (21/120) compared with 5.4% (2/37) for ER-negative breast cancer (p = 0.108) and 9.6% (429/4451) in the general population (p = 0.0077). Adrenal-permissive genotype frequency for estrogen-driven postmenopausal breast cancer was validated using Cambridge and TCGA datasets: 14.4% (56/389) compared with 6.0% (9/149) for ER-negative breast cancer (p = 0.007) and the general population (p = 0.005). Circulating androstenedione concentration was higher with the adrenal-permissive genotype (p = 0.03).

CONCLUSION: Adrenal-permissive genotype is associated with estrogen-driven postmenopausal breast cancer. These findings link genetic inheritance of endogenous estrogen exposure to estrogen-driven breast cancer.

FUNDING: NCI.

PMID:34520399 | DOI:10.1172/jci.insight.150403

Expression of Glucose Metabolism-Related Proteins in Adrenal Neoplasms

Fetched: September 15th, 2021, 5:00am GMT by Eun Kyung Kim

Pathobiology. 2021 Sep 9:1-10. doi: 10.1159/000518208. Online ahead of print.

ABSTRACT

PURPOSE: The aim of this study was to investigate the expression patterns of glucose metabolism-related proteins and their clinicopathologic implications in adrenal cortical neoplasms (ACN) and pheochromocytoma (PCC).

METHODS: Immunohistochemical staining was performed to evaluate glucose metabolism-related proteins (GLUT1, CAIX, hexokinase II, G6PDH, PHGDH, and SHMT1) in 132 ACN cases (115 adrenal cortical adenoma [ACA] and 17 adrenal cortical carcinoma [ACC]) and 189 PCC cases.

RESULTS: Expression levels of GLUT1 in tumor cells ([T]; p < 0.001), GLUT1 in stromal cells ([S]; p < 0.001), G6PDH (p < 0.001), and SHMT1 (p = 0.002) were higher in ACN than in PCC. GLUT1 (T; p = 0.045) and PHGDH (p = 0.043) levels were higher in ACC than in ACA. In a univariate analysis of ACN, GLUT1 (T; p = 0.017), CAIX (S; p = 0.003), and PHGDH (p = 0.009) levels were correlated with a shorter overall survival (OS). GLUT1 (T; p = 0.001) and PHGDH (p < 0.001) were related to a shorter OS in PCC. GLUT1 (T) positivity (p = 0.043) in ACN predicted a poor OS in a multivariate Cox analysis. In PCC, high GAPP score (p = 0.026), GLUT1 (T; p = 0.002), and PHGDH (p < 0.001) were independent prognostic factors for poor OS.

CONCLUSIONS: The adrenal gland tumors ACN and PCC had different expression patterns of glucose metabolism-related proteins (GLUT1, G6PDH, and SHMT1), with higher expression levels in ACN than in PCC. GLUT1 and PHGDH were significant prognostic factors in these adrenal neoplasms.

PMID:34518477 | DOI:10.1159/000518208

Adrenal pheochromocytoma with involvement of aorta and left renal artery: salvaged with adrenalectomy and nephrectomy

Fetched: September 15th, 2021, 5:00am GMT by Shekhar Sathaye

BMJ Case Rep. 2021 Sep 12;14(9):e244297. doi: 10.1136/bcr-2021-244297.

ABSTRACT

Large adrenal pheochromocytomas encasing the renal artery are a rare entity. The management of such challenging cases is surgical resection. The involvement of renal tissue and renal artery may necessitate meticulous dissection and concomitant nephrectomy. Here, we present a case of 41-year-old man diagnosed with left adrenal pheochromocytoma with complete encasement of left renal artery and partial encasement of aorta. Open left adrenalectomy and nephrectomy was performed after adequate preoperative optimisation. The patient is doing well at 6-month follow-up. Large adrenal pheochromocytoma with renal involvement is a rare presentation and requires optimal preoperative imaging, adequate preoperative alpha and beta blockade and meticulous surgical technique.

PMID:34511410 | DOI:10.1136/bcr-2021-244297

Practice of laparoscopic anatomical adrenalectomy

Fetched: September 15th, 2021, 5:00am GMT by L Lei

Zhonghua Yi Xue Za Zhi. 2021 Sep 14;101(34):2723-2727. doi: 10.3760/cma.j.cn112137-20210429-01036.

ABSTRACT

On the basis of existing laparoscopic transabdominal adrenalectomy, this article described a safe and reliable surgical method for the treatment of small adrenal lesions-laparoscopic anatomical adrenalectomy (LAA), and retrospectively analyzed the clinical data of 74 patients who had undergone LAA. All patients had no signs of recurrence on imaging. LAA has high safety and feasibility, clear intraoperative anatomical layers, good spatial operability, and low postoperative complications. LAA provides a more reliable option for the treatment of small adrenal diseases.

PMID:34510880 | DOI:10.3760/cma.j.cn112137-20210429-01036

Value of serum parathyroid hormone in the diagnosis of primary aldosteronism

Fetched: September 15th, 2021, 5:00am GMT by Y J Liu

Zhonghua Yi Xue Za Zhi. 2021 Sep 14;101(34):2674-2680. doi: 10.3760/cma.j.cn112137-20210111-00088.

ABSTRACT

Objective: To explore the value of serum parathyroid hormone (PTH) in the diagnosis of primary aldosteronism (PA) and to investigate an optimal cut-off of serum PTH to distinguish PA from nonfunctional adrenal tumor (NFA). Methods: The clinical data of patients with adrenal incidentaloma in Chinese PLA General Hospital from January 1, 2017 to December 31, 2019 were collected. The data of PA and NFA by clinical characteristics and evaluation on endocrine function were retrospectively analyzed. The logistic regression model was used to find the potential risk factors of elevated PTH. The receiver operating characteristic(ROC) curve was used to evaluate the efficacy of PTH in diagnosis of PA and to explore the best cut-off value. Results: A total of 773 patients were included. There were 356 PA patients (203 males, 57.0%), aged (50±11) years and 417 NFA patients (219 males, 52.5%), aged (51±12) years. The serum PTH level in patients with PA was significantly higher than that in patients with NFA [63.1 (48.4, 80.3) ng/L vs 41.7 (34.1, 51.7) ng/L, P<0.05], as well as the proportion of patients with elevated PTH level (47.8% vs 7.2%, P<0.05). Logistic regression analysis showed that having PA and deficiency of Vitamin D were risk factors for PTH elevation (both P<0.05). The ROC curve showed that the best cut-off value of PTH for the diagnosis of PA in patients with vitamin D deficiency was 56.44 ng/L, with a sensitivity of 66.5% and a specificity of 83.0%, and that in patients with normal vitamin D was 48.81 ng/L, with a sensitivity of 70.5% and a specificity of 72.6%. Conclusions: Patients with PA tend to show increased levels of serum PTH compared with NFA patients. The level of serum PTH can be used as one of the valuable indexes in screening of PA.

PMID:34510873 | DOI:10.3760/cma.j.cn112137-20210111-00088

Permalink for 'Combination treatment with trastuzumab and crizotinib in metastatic gastric cancer harboring Her-2 amplification and c-MET amplification: A case report'

Combination treatment with trastuzumab and crizotinib in metastatic gastric cancer harboring Her-2 amplification and c-MET amplification: A case report

Fetched: September 14th, 2021, 5:00am GMT by Mingsheng Liu

Medicine (Baltimore). 2021 Sep 10;100(36):e27017. doi: 10.1097/MD.0000000000027017.

ABSTRACT

RATIONALE: Metastatic gastric cancer patients with poor eastern cooperative oncology group performance status (PS) (≥3) were lack of effective anti-tumor strategies. They always lived with poor PS, severe and multiple symptoms, and usually resulted in extremely limited survival time. Herein, we reported a patient diagnosed with gastric cancer metastasized to multiple bones, along with lymphangitis carcinomatosa in lungs, harboring Her-2 and c-MET amplification with poor PS, positively responded to combinational therapy with trastuzumab and crizotinib.

PATIENT CONCERNS: The patient complained of persistent cough and fatigue for 2 months, otherwise, she denied smoking, alcohol history, or any other medical or family history.

DIAGNOSIS: With the biopsy results from gastroscopy, as well as computer tomography for chest and abdomen, the patient was diagnosed as gastric adenocarcinoma, with metastasis on lungs, left adrenal gland, retroperitoneal lymph nodes, and multiple bones.

INTERVENTIONS: Because of the poor PS (PS = 3), as well as Her-2 and c-MET amplification, the patient received combination treatment with trastuzumab and crizotinib as salvage strategy.

OUTCOMES: After 2 months' exposure of trastuzumab and crizotinib, symptoms including persistent cough, and chest distress were alleviated significantly. Simultaneously, chest computer tomography showed significant dissipation of lymphangitis carcinomatosa, as well as apparent reduction of pleural effusion. No adverse reactions including nausea, vomiting, diarrhea, or hypertension was observed during the following 2 months.

LESSONS: The present case suggested that combinational therapy with trastuzumab and crizotinib might be effective in metastatic gastric cancer patients harboring Her-2 and c-MET amplification, even with a poor PS. It was also implied that gene sequencing might be valuable, especially in patients with limited treatment strategies.

PMID:34516491 | PMC:PMC8428754 | DOI:10.1097/MD.0000000000027017

A Novel Liquid Biopsy (NETest) identifies Paragangliomas and Pheochromocytomas with High Accuracy

Fetched: September 14th, 2021, 5:00am GMT by Karel Pacak

Endocr Relat Cancer. 2021 Sep 1:ERC-21-0216.R1. doi: 10.1530/ERC-21-0216. Online ahead of print.

ABSTRACT

Pheochromocytomas and paragangliomas (PHEOs/PGLs) represent diagnostically challenging and complex neuroendocrine tumors (NETs). Current biomarker tests for PHEOs/PGLs are technically complex or limited. We assessed the diagnostic utility of a NET-specific 51-marker gene blood assay (NETest) in patients with PHEOs/PGLs (n=81), including 10 pediatric patients, and age-/gender-matched controls (n=142) using a prospective case:control (1:2) analysis. mRNA was measured (qPCR) and results scaled 0-100 (ULN<20). Receiver Operating Curve (ROC) and non-parametric (Mann-Whitney) were used for analyses (2-tailed). All data is presented as mean±SEM. NETest accuracy for PHEO/PGL diagnosis was 100%. PHEO/PGL scores were 70±3 versus 8.5±1 in controls (p<0.0001) and ROC analysis was 0.99±0.004 (p<0.0001). Diagnostic metrics were 94% accurate, 100% sensitive, and 92% specific. Imaging correlation with 68Ga-PET-SSA was 100%. NETest levels in PHEOs (n=26) were significantly (p<0.0001) elevated (83±4) versus 66±4 in PGLs (n=40) and mixed PHEOs/PGLs (n=5: 37±3). Adrenal-derived tumors (n=30) exhibited higher scores (76±5) than extra-adrenal-derived tumors (66±4, p<0.05). Cluster 2 tumors exhibited significantly (p=0.034) elevated NETest levels (n=4: 92±2) versus Cluster 1 tumors (n=35: 69±4). Regulatory pathway analysis identified elevated RAS-RAF, metastatic, pluripotential, neural and secretory gene cluster levels (p<0.05) in PHEOs compared to PGLs. Cluster 2 PPGLs exhibited elevated (p=0.046) levels of growth-factor signaling genes compared to cluster 1. The PHEOs/PGLs in the pediatric cohort (n=10) were all NETest-positive (81±8) and exhibited a gene expression profile spectrum analogous to adults. Circulating NET transcript analysis identifies PHEOs/PGLs with 100% efficacy and is likely to have clinical utility in the diagnosis and management of PHEO/PGL patients.

PMID:34515661 | DOI:10.1530/ERC-21-0216

Permalink for 'An Unusual Case of Hypopituitarism as an Adverse Effect of Vandetanib and Remission of Breast Metastases in a Patient with Medullary Thyroid Cancer'

An Unusual Case of Hypopituitarism as an Adverse Effect of Vandetanib and Remission of Breast Metastases in a Patient with Medullary Thyroid Cancer

Fetched: September 14th, 2021, 5:00am GMT by Rosa M García-Moreno

Oncol Res Treat. 2021 Aug 18:1-5. doi: 10.1159/000518673. Online ahead of print.

ABSTRACT

INTRODUCTION: Tyrosine kinase inhibitors have been a breakthrough in the treatment of advanced medullary thyroid cancer (MTC), and they can prolong progression-free survival (PFS).

CASE PRESENTATION: A patient with MTC and metastatic spread to the lymph nodes, lungs, bones, breast, and cerebellum started treatment with vandetanib. During treatment, she developed secondary adrenal insufficiency and hypogonadotropic hypogonadism. After 9 years of vandetanib therapy, the disease has not progressed and the patient maintains a complete response of the breast metastases and a partial response of the other metastatic lesions.

CONCLUSION: To our knowledge, this is the first reported case of secondary adrenal insufficiency and hypogonadotropic hypogonadism related to therapy with vandetanib. Moreover, the prolonged PFS and the complete disappearance of some of the metastatic lesions in this patient are truly unusual.

PMID:34515201 | DOI:10.1159/000518673

Impact of Central Nervous System International Prognostic Index on the Treatment of Diffuse Large B Cell Lymphoma

Fetched: September 14th, 2021, 5:00am GMT by Mohammad Ma'koseh

Cureus. 2021 Aug 1;13(8):e16802. doi: 10.7759/cureus.16802. eCollection 2021 Aug.

ABSTRACT

Background The central nervous system international prognostic index (CNS-IPI) is being used widely for the identification of patients with diffuse large B cell lymphoma (DLBCL) with a high risk of central nervous system (CNS) relapse. The aim of our study is to confirm the value of the CNS-IPI in predicting CNS relapse in our young study population and to evaluate its impact on the selection of patients for CNS prophylaxis. Methods We retrospectively reviewed patients diagnosed with DLBCL who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) regimen from January 2010 till December 2018. Correlation between CNS-IPI and cumulative incidence of CNS relapse and time to CNS relapse was examined through Kaplan-Meier plots. Median time to CNS relapse and median overall survival after CNS relapse were also estimated using the Kaplan-Meier plots. Results A total of 354 patients were included. The median age was 46 years. Overall, 5% of the patients developed CNS relapse. Median survival after CNS relapse was seven months. Two-year CNS relapse rates according to CNS-IPI were 0.7%, 5.1%, and 26% for low, intermediate, and high-risk, groups respectively. On multivariate analysis, poor performance status (p=0.045), involvement of two or more extranodal sites (p= 0.021), involvement of bone marrow (p= 0.029), and renal or adrenal glands (p= 0.006) significantly correlated with CNS relapse. Considering the CNS-IPI and high-risk anatomical sites (breast, uterus, testis, and epidural space), 26% of our patients with DLBCL would have needed prophylaxis. Conclusion Although CNS-IPI helps in better selection of DLBCL patients for CNS prophylaxis, it can possibly increase the number of patients exposed to unnecessary prophylaxis. More investigational biomarkers are needed to better refining high-risk patients.

PMID:34513408 | PMC:PMC8407468 | DOI:10.7759/cureus.16802

How to Differentiate Benign from Malignant Adrenocortical Tumors?

Fetched: September 12th, 2021, 5:00am GMT by Charlotte L Viëtor

Cancers (Basel). 2021 Aug 30;13(17):4383. doi: 10.3390/cancers13174383.

ABSTRACT

Adrenocortical carcinoma (ACC) is a rare cancer with a poor prognosis. Adrenal incidentalomas are, however, commonly identified in clinical practice. Discrimination between benign and malignant adrenal tumors is of great importance considering the large differences in clinical behavior requiring different strategies. Diagnosis of ACC starts with a thorough physical examination, biochemical evaluation, and imaging. Computed tomography is the first-level imaging modality in adrenal tumors, with tumor size and Hounsfield units being important features for determining malignancy. New developments include the use of urine metabolomics, also enabling discrimination of ACC from adenomas preoperatively. Postoperatively, the Weiss score is used for diagnosis of ACC, consisting of nine histopathological criteria. Due to known limitations as interobserver variability and lack of accuracy in borderline cases, much effort has been put into new tools to diagnose ACC. Novel developments vary from immunohistochemical markers and pathological scores, to markers at the level of DNA, methylome, chromosome, or microRNA. Molecular studies have provided insights into the most promising and most frequent alterations in ACC. The use of liquid biopsies for diagnosis of ACC is studied, although in a small number of patients, requiring further investigation. In this review, current diagnostic modalities and challenges in ACC will be addressed.

PMID:34503194 | PMC:PMC8431066 | DOI:10.3390/cancers13174383

Permalink for 'Cutaneous metastasis of primary diffuse large B-cell lymphoma of the central nervous system developing four years after complete remission: Diagnosis confirmed by comparison of clones'

Cutaneous metastasis of primary diffuse large B-cell lymphoma of the central nervous system developing four years after complete remission: Diagnosis confirmed by comparison of clones

Fetched: September 10th, 2021, 5:00am GMT by Bansri M Patel

J Cutan Pathol. 2021 Sep 9. doi: 10.1111/cup.14129. Online ahead of print.

ABSTRACT

B-cell lymphoma of the central nervous system (CNS) is a rare malignancy with diffuse large B-cell lymphoma (DLBCL) variant being most common. Although DLBCL has a high propensity to relapse locally within the CNS, only a few cases of cutaneous metastasis have been described in the literature. We present a unique case of cutaneous metastasis of a primary DLBCL of the CNS in a 79-year-old man who was in clinical remission for four years until presenting with a lesion in the left adrenal gland and cutaneous nodules on the left flank. Skin biopsy specimen revealed a diffuse dermal infiltrate of atypical B-cell lymphocytes with expression of CD20, BCL-2, BCL-6, and MUM-1, suggestive of DLBCL. For differentiation between another primary or a recurrent process, immunoglobulin kappa (IgK) light chain gene rearrangement was performed and demonstrated that the DLBCL of the skin and CNS were of the same clonal origin. Restaging CT after initiating chemotherapy and daily ibrutinib showed complete resolution of the left adrenal mass and resolving cutaneous lesions. Our case demonstrates the rare, late cutaneous metastasis of DLBCL of the CNS and highlights the importance of genetic testing for the distinction between the primary and secondary lesions. This article is protected by copyright. All rights reserved.

PMID:34498750 | DOI:10.1111/cup.14129

Delayed positive COVID19 nasopharyngeal test, a case study with clinical and pathological correlation

Fetched: September 10th, 2021, 5:00am GMT by Lei Zhang

BMC Pulm Med. 2021 Aug 31;21(1):278. doi: 10.1186/s12890-021-01643-y.

ABSTRACT

BACKGROUND: There are various reasons for delayed positive nasopharyngeal PCR tests for coronavirus disease 2019 (COVID19) in not only asymptomatic but also severely diseased patients. The pathophysiological attributes are not known. We explore this possibility through a case report.

CASE PRESENTATION: A 64-year-old male with history of pulmonary fungal infection, asthma and chronic pulmonary obstructive disease (COPD), diabetes, coronary artery disease presented with shortness of breath, fever and chest image of ground opacity, reticular interstitial thickening, highly suspicious for COVID19. However, nasopharyngeal swab tests were discordantly negative for four times in two weeks, and IgG antibody for COVID19 was also negative. However, serum IgE level was elevated. No other pathogens are identified. His symptoms deteriorated despite corticosteroid, antibiotics and bronchodilator treatment. Bronchoalveolar lavage (BAL) and open lung wedge biopsy were performed for etiology diagnosis. They demonstrated COVID19 viral RNA positive fibrosing organizing pneumonia with respiratory tract damage characterized by suspicious viral cytopathic effect, mixed neutrophilic, lymphoplasmacytic, histiocytic and eosinophilic inflammation and fibrosis besides expected asthma and COPD change. One week later, repeated COVID19 nasopharyngeal tests on day 40 and day 49 became positive.

CONCLUSION: Our case and literature review indicate that allergic asthma and associated high IgE level together with corticosteroid inhalation might contribute to the delayed positive nasopharyngeal swab in upper airway; COPD related chronic airways obstruction and the addition of fibrosis induced ventilator dependence and poor prognosis in COVID19 pneumonia, and should be therapeutically targeted besides antiviral therapy.

PMID:34465321 | PMC:PMC8406010 | DOI:10.1186/s12890-021-01643-y

Permalink for 'Case Report: Consecutive Adrenal Cushing's Syndrome and Cushing's Disease in a Patient With Somatic CTNNB1, USP8, and NR3C1 Mutations'

Case Report: Consecutive Adrenal Cushing's Syndrome and Cushing's Disease in a Patient With Somatic CTNNB1, USP8, and NR3C1 Mutations

Fetched: September 8th, 2021, 5:00am GMT by Mario Detomas

Front Endocrinol (Lausanne). 2021 Aug 20;12:731579. doi: 10.3389/fendo.2021.731579. eCollection 2021.

ABSTRACT

The occurrence of different subtypes of endogenous Cushing's syndrome (CS) in single individuals is extremely rare. We here present the case of a female patient who was successfully cured from adrenal CS 4 years before being diagnosed with Cushing's disease (CD). The patient was diagnosed at the age of 50 with ACTH-independent CS and a left-sided adrenal adenoma, in January 2015. After adrenalectomy and histopathological confirmation of a cortisol-producing adrenocortical adenoma, biochemical hypercortisolism and clinical symptoms significantly improved. However, starting from 2018, the patient again developed signs and symptoms of recurrent CS. Subsequent biochemical and radiological workup suggested the presence of ACTH-dependent CS along with a pituitary microadenoma. The patient underwent successful transsphenoidal adenomectomy, and both postoperative adrenal insufficiency and histopathological workup confirmed the diagnosis of CD. Exome sequencing excluded a causative germline mutation but showed somatic mutations of the β-catenin protein gene (CTNNB1) in the adrenal adenoma, and of both the ubiquitin specific peptidase 8 (USP8) and the glucocorticoid receptor (NR3C1) genes in the pituitary adenoma. In conclusion, our case illustrates that both ACTH-independent and ACTH-dependent CS may develop in a single individual even without evidence for a common genetic background.

PMID:34489873 | PMC:PMC8417750 | DOI:10.3389/fendo.2021.731579

Mesenteric Extra-adrenal Paraganglioma - An Unusual Cause of Intermittent Abdominal Pain

Fetched: September 8th, 2021, 5:00am GMT by Wade Stinson

S D Med. 2021 Aug;74(8):376-379.

ABSTRACT

Paragangliomas are non-epithelial tumors of neuroendocrine origin that arise from the paraganglia of the sympathetic and parasympathetic nervous system. These paraganglia cells are derived from the neural crest and can be found anywhere in the body where paraganglia exist. Paragangliomas are rare tumors. It is estimated that the incidence of pheochromocytoma (intra-adrenal paraganglioma) and extra-adranal paraganglioma is 0.8 per 100,000 person years. It is commonly stated that 10 percent of paragangliomas are extra-adrenal. The majority of parasymphathetic paragangliomas reside in the skull base and along the vagus and glossopharyngeal nerves, whereas the majority of sympathetic paragangliomas can be found in the abdomen. Paragangliomas found in the mesentery are exceedingly rare, with 12 reported cases identified in the literature. We present the case of a 61-year-old female who presented to our institution with a suspected superior mesenteric artery aneurysm who was ultimately found to have an extra-adrenal paraganglioma within the small bowel mesentery of the right lower quadrant of the abdomen.

PMID:34461004

Permalink for 'Impact of postoperative radiotherapy on the outcomes of resected adrenocortical carcinoma-a real-world, population-based study'

Impact of postoperative radiotherapy on the outcomes of resected adrenocortical carcinoma-a real-world, population-based study

Fetched: September 4th, 2021, 5:00am GMT by Omar Abdel-Rahman

Strahlenther Onkol. 2021 Sep 2. doi: 10.1007/s00066-021-01838-6. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the impact of postoperative radiotherapy on the outcomes of resected adrenocortical carcinoma in a real-world setting.

METHODS: The Surveillance, Epidemiology, and End Results Research Plus database was accessed, and patients with resected non-metastatic adrenocortical carcinoma diagnosed 2010-2015 were reviewed. Kaplan-Meier estimates and log-rank testing were used to examine the impact of postoperative radiotherapy on overall and cancer-specific survival. Multivariable Cox regression analysis was used to explore factors associated with overall and cancer-specific survival.

RESULTS: A total of 294 patients were included in the final analysis, including 60 patients (20.4%) who received postoperative radiotherapy. Using Kaplan-Meier estimates, individuals who received postoperative radiotherapy have better overall survival (P = 0.002). Multivariable cox regression analysis showed that the following factors were associated with worse overall survival: older age (HR: 1.01; 95% CI: 1.00-1.03), male sex (HR for female sex versus male sex: 0.61; 95% CI: 0.43-0.85), and non-receipt of postoperative radiation therapy (HR: 2.29; 95% CI: 1.38-3.77). Systemic therapy was not associated with differences in overall survival (HR: 0.77; 95% CI: 0.54-1.10). Likewise, the following factors were associated with worse cancer-specific survival: male sex (HR for female sex versus male sex: 0.60; 95% CI: 0.41-0.88), non-receipt of postoperative radiation therapy (HR: 2.17; 95% CI: 1.27-3.70), and receipt of perioperative systemic therapy (HR: 0.67; 95% CI: 0.45-0.99).

CONCLUSION: Postoperative radiotherapy following resection of adrenocortical carcinoma is associated with better overall and cancer-specific survival.

PMID:34476529 | DOI:10.1007/s00066-021-01838-6

Permalink for 'Concurrent use of nivolumab and radiotherapy for patients with metastatic non-small cell lung cancer and renal cell carcinoma with oligometastatic disease progression on nivolumab'

Concurrent use of nivolumab and radiotherapy for patients with metastatic non-small cell lung cancer and renal cell carcinoma with oligometastatic disease progression on nivolumab

Fetched: September 4th, 2021, 5:00am GMT by Jawaher Ansari

Mol Clin Oncol. 2021 Oct;15(4):214. doi: 10.3892/mco.2021.2376. Epub 2021 Aug 23.

ABSTRACT

Checkpoint inhibitors (CPIs), such as nivolumab, have transformed the treatment paradigm for patients with metastatic non-small cell lung cancer (mNSCLC) and metastatic renal cell carcinoma (mRCC). The combination of CPIs and radiotherapy (RT) constitutes a multimodal treatment approach that may work synergistically and facilitate augmented systemic responses. The aim of the present retrospective study was to assess the efficacy and safety of continuation of nivolumab treatment with the addition of RT in patients with mNSCLC and mRCC who develop oligometastatic disease progression on single-agent nivolumab. All patients with mNSCLC and mRCC who received nivolumab at the Department of Oncology, Prince Sultan Military Medical City (Riyadh, Saudi Arabia) between November 2016 and April 2018 were identified. The records of patients who developed oligometastatic disease progression during nivolumab treatment and were subsequently treated with RT, with nivolumab continued beyond disease progression, were retrospectively reviewed. Details of RT, clinical outcomes and toxicity data were collected. Of the 96 patients who received nivolumab, 22 received multiple courses of RT. A total of 39 sites were irradiated: Bone (n=15), lung (n=9), brain (n=8), adrenal gland (n=2), renal bed (n=2), skin (n=1), ethmoid sinus (n=1) and scalp (n=1). Partial response and complete response were noted at 25 (64%) and 3 (8%) sites, respectively. Stable disease was noted at 6 sites (15%) and disease progression was noted at 5 sites (13%). The median time on nivolumab from the date of the first fraction of RT was 4.5 months (range, 1.5-29 months) for patients with mNSCLC and 5 months (range, 1-38.5 months) for patients with mRCC. No patients developed grade 3-4 toxicities. Grade 2 pneumonitis was noted in 3 patients receiving lung RT. The addition of RT appeared to initiate a response and prolong the duration of nivolumab treatment. Therefore, the combination of nivolumab and RT was found to be well tolerated, with response rates exceeding those in published studies of nivolumab monotherapy.

PMID:34476098 | PMC:PMC8408674 | DOI:10.3892/mco.2021.2376

Impact of prostate cancer on the nervous system: two different cases and a review of the literature.

Fetched: September 4th, 2021, 5:00am GMT by Francisco Cedeira

Arch Esp Urol. 2021 Sep;74(7):715-719.

ABSTRACT

We present two different cases of involvement of the nervous system due to prostate cancer. We know that atypical metastases can also affect supraclavicular lymphatics, adrenal gland and testicles. In these cases we present a typical places in the nervous system. We musttake into account that sometimes the shape the presentation of symptoms can be confused with other pathologies. In some cases, this type of patient has never had a urological check-up and in our sagacity as doctors we come to find the origin of the problem: the prostate.

PMID:34472442

Permalink for 'Pediatric Multiple Endocrine Neoplasia Type 2B with Pheochromocytoma Diagnosed after Perforation of a Colonic Diverticulum : A Case Report'

Pediatric Multiple Endocrine Neoplasia Type 2B with Pheochromocytoma Diagnosed after Perforation of a Colonic Diverticulum : A Case Report

Fetched: September 4th, 2021, 5:00am GMT by Yosuke Sekii

Hinyokika Kiyo. 2021 Aug;67(8):363-366. doi: 10.14989/ActaUrolJap_67_8_363.

ABSTRACT

A 12-year-old girl was found to have decending colon diverticulum perforation and retroperitoneal abscess on computed tomography (CT) carried out to determine the cause of fever and stomachache. CT-guided drainage tube placement was performed. She was suspected of having MEN2B from her specific facial appearance, Marfan-like body shape and lingual mucosa neuroma. Cervical ultrasonography and serum tumor marker revealed medullary thyroid carcinoma and metastasis to cervical lymph node. Genetic examination revealed a mutation of RET gene codon 918. Therefore, she was diagnosed as having MEN2B. Laboratory data showed elevated urinary catecholamines. Metaiodobenzylguanidine (MIBG) adrenal scintigraphy showed bilateral adrenal uptake and a definitive diagnosis of bilateral adrenal pheochromocytomas was made. Discharge from the drainage tube persisted and it was difficult to continue conservative treatment. Therefore, laparoscopic bilateral adrenalectomy and transverse colon colostomy were performed. Subsequently, total thyroidectomy and cervical lymph node dissection were performed. At five years of follow up, bilateral lung metastases were observed, but the serum calcitonin level was normal and the patient is under observation.

PMID:34472317 | DOI:10.14989/ActaUrolJap_67_8_363

Bilateral adrenal metastasis of renal cell carcinoma 4 years after radical nephrectomy: A case report and review of literature

Fetched: September 4th, 2021, 5:00am GMT by Yingjie Li

Medicine (Baltimore). 2021 Aug 6;100(31):e26838. doi: 10.1097/MD.0000000000026838.

ABSTRACT

RATIONALE: Renal cell carcinoma (RCC) almost metastasizes to every organ, the possibility of adrenal metastasis is relatively low in patients that have undergone radical nephrectomy, only a few cases of bilateral adrenal metastasis are reported on literature. Although surgical treatment of metastases from RCC is preferred and contributes to the rate of survival, it is considered challenging to manage such cases due to the rarity of bilateral metastasis to the adrenal glands.

PATIENT CONCERNS: A 64-year-old Manchus female presented with an incidental ultrasonic finding of a left adrenal mass 4 years after radical nephrectomy for left renal cell carcinoma.

DIAGNOSIS: Abdominal contrast enhanced CT scan revealed bilateral adrenal masses, suggesting metastatic lesion. Examinations indicated neither local recurrence nor distant metastasis anywhere have been detected by whole body Positron Emission Tomography/Computed Tomography (PET/CT) scan except high radioactive uptake in bilateral adrenal glands.

INTERVENTIONS: Metachronous bilateral adrenalectomy was taken and laparoscopic right adrenalectomy was first performed. She was discharged home on third postoperative day. Pathological examination revealed metastatic renal cell carcinoma. Two months later she was performed laparoscopic left adrenalectomy.

OUTCOMES: The patient healed without obvious complications and no tumor recurrence.

LESSONS: Bilateral metastatic adrenal recurrence from RCC is very rare. Early diagnosis of adrenal metastasis is challenging because they are usually silent both anatomically and functionally. Surgical intervention is a wise option for these patients that may improve survival, and metachronous bilateral adrenalectomy is proved to be safe and effective.

PMID:34397852 | PMC:PMC8341217 | DOI:10.1097/MD.0000000000026838

Permalink for 'Clinical management and outcomes associated with etoposide, doxorubicin, and cisplatin plus mitotane treatment in metastatic adrenocortical carcinoma: a single institute experience'

Clinical management and outcomes associated with etoposide, doxorubicin, and cisplatin plus mitotane treatment in metastatic adrenocortical carcinoma: a single institute experience

Fetched: September 2nd, 2021, 5:00am GMT by Masaki Uchihara

Int J Clin Oncol. 2021 Sep 1. doi: 10.1007/s10147-021-02021-8. Online ahead of print.

ABSTRACT

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and aggressive disease that is often diagnosed at an advanced stage. There is no standard treatment for metastatic ACC; EDP-M (etoposide, doxorubicin, and cisplatin plus mitotane) is one treatment option. A randomized controlled trial (FIRM-ACT) evaluating the efficacy of EDP-M showed progression-free survival (PFS) was 5.0 months, overall survival (OS) was 14.8 months, the response rate was 19%, and adrenal insufficiency occurred in 3.4% of patients. However, the efficacy and safety of this regimen in Asia are not fully reported.

METHODS: We retrospectively analyzed 43 patients diagnosed with metastatic ACC at the National Cancer Center Hospital between 1997 and 2020. We evaluated PFS, OS, and response in 17 patients who received EDP-M as first-line therapy.

RESULTS: The median age at treatment initiation was 45 years (range 18-74). Eight patients (47%) had autonomous hormone production, including six patients with hypercortisolism. The best response of partial response and stable disease was seen in two (12%) and ten (59%) patients, respectively. The median PFS was 6.2 months [95% confidence interval (CI): 4.3-10.0]. The median OS was 15.4 months (95% CI 11.6-not reached). Three patients received only one cycle due to adverse effects associated with hypercortisolism. Grade 3/4 adverse events associated with adrenal insufficiency occurred in three (17%) cases, resulting in EDP-M discontinuation.

CONCLUSIONS: The EDP-M regimen had similar PFS to that observed in FIRM-ACT. Adrenal insufficiency was more frequent in the current study, but this could be managed with supportive endocrinological care such as cortisol replacement.

PMID:34468885 | DOI:10.1007/s10147-021-02021-8

Prognostic model of long-term advanced stage (IIIB-IV) EGFR mutated non-small cell lung cancer (NSCLC) survivors using real-life data

Fetched: September 2nd, 2021, 5:00am GMT by Lourdes Gutiérrez

BMC Cancer. 2021 Aug 31;21(1):977. doi: 10.1186/s12885-021-08713-8.

ABSTRACT

BACKGROUND: There is a lack of useful diagnostic tools to identify EGFR mutated NSCLC patients with long-term survival. This study develops a prognostic model using real world data to assist clinicians to predict survival beyond 24 months.

METHODS: EGFR mutated stage IIIB and IV NSCLC patients diagnosed between January 2009 and December 2017 included in the Spanish Lung Cancer Group (SLCG) thoracic tumor registry. Long-term survival was defined as being alive 24 months after diagnosis. A multivariable prognostic model was carried out using binary logistic regression and internal validation through bootstrapping. A nomogram was developed to facilitate the interpretation and applicability of the model.

RESULTS: 505 of the 961 EGFR mutated patients identified in the registry were included, with a median survival of 27.73 months. Factors associated with overall survival longer than 24 months were: being a woman (OR 1.78); absence of the exon 20 insertion mutation (OR 2.77); functional status (ECOG 0-1) (OR 4.92); absence of central nervous system metastases (OR 2.22), absence of liver metastases (OR 1.90) or adrenal involvement (OR 2.35) and low number of metastatic sites (OR 1.22). The model had a good internal validation with a calibration slope equal to 0.781 and discrimination (optimism corrected C-index 0.680).

CONCLUSIONS: Survival greater than 24 months can be predicted from six pre-treatment clinicopathological variables. The model has a good discrimination ability. We hypothesized that this model could help the selection of the best treatment sequence in EGFR mutation NSCLC patients.

PMID:34465283 | PMC:PMC8406921 | DOI:10.1186/s12885-021-08713-8

Adrenal hemorrhage and hemorrhagic masses; diagnostic workup and imaging findings

Fetched: September 1st, 2021, 5:00am GMT by Mohamed Badawy

Br J Radiol. 2021 Aug 31:20210753. doi: 10.1259/bjr.20210753. Online ahead of print.

ABSTRACT

Adrenal hemorrhage (AH) is a rare condition. It can be traumatic or non-traumatic. Most common causes are septicemia, coagulopathy or bleeding diathesis, and underlying neoplasms. Other reported less common causes of AH are COVID-19 and neonatal stress. Clinical diagnosis of AH is challenging due to its non-specific presentation and occurrence in the setting of acute medical illness. Therefore, most cases are diagnosed incidentally on imaging. Having high clinical suspicion in the proper clinical setting for AH is crucial to avoid life-threatening adrenal insufficiency that occurs in 16-50% of patients with bilateral AH. We discuss the clinical situations that predispose to AH, review the imaging features on different imaging modalities, highlight a variety of clinical cases, imaging features that should be concerning for an underlying neoplasm, and outline the potential role of interventional radiology in management of AH.

PMID:34464549 | DOI:10.1259/bjr.20210753

Primary Adrenal Insufficiency Due to Bilateral Adrenal Infarction in COVID-19

Fetched: September 1st, 2021, 5:00am GMT by Iza F R Machado

J Clin Endocrinol Metab. 2021 Jul 29:dgab557. doi: 10.1210/clinem/dgab557. Online ahead of print.

ABSTRACT

CONTEXT: Coronavirus disease 2019 (COVID-19) is a proinflammatory and prothrombotic condition, but its impact on adrenal function has not been adequately evaluated.

CASE REPORT: A 46-year-old woman presented with abdominal pain, hypotension, and skin hyperpigmentation after COVID-19 infection. The patient had hyponatremia, serum cortisol <1.0 µg/dL, adrenocorticotropin (ACTH) of 807 pg/mL, and aldosterone <3 ng/dL. Computed tomography (CT) findings of adrenal enlargement with no parenchymal and minimal peripheral capsular enhancement after contrast were consistent with bilateral adrenal infarction. The patient had autoimmune hepatitis and positive antiphospholipid antibodies, but no previous thrombotic events. The patient was treated with intravenous hydrocortisone, followed by oral hydrocortisone and fludrocortisone.

DISCUSSION: We identified 9 articles, including case reports, of new-onset adrenal insufficiency and/or adrenal hemorrhage/infarction on CT in COVID-19. Adrenal insufficiency was hormonally diagnosed in 5 cases, but ACTH levels were measured in only 3 cases (high in 1 case and normal/low in other 2 cases). Bilateral adrenal nonhemorrhagic or hemorrhagic infarction was identified in 5 reports (2 had adrenal insufficiency, 2 had normal cortisol levels, and 1 case had no data). Interestingly, the only case with well-characterized new-onset acute primary adrenal insufficiency after COVID-19 had a previous diagnosis of antiphospholipid syndrome. In our case, antiphospholipid syndrome diagnosis was established only after the adrenal infarction triggered by COVID-19.

CONCLUSION: Our findings support the association between bilateral adrenal infarction and antiphospholipid syndrome triggered by COVID-19. Therefore, patients with positive antiphospholipid antibodies should be closely monitored for symptoms or signs of acute adrenal insufficiency during COVID-19.

PMID:34463766 | DOI:10.1210/clinem/dgab557

SMARCA4-Deficient Undifferentiated Tumor Diagnosed on Adrenal Sampling

Fetched: September 1st, 2021, 5:00am GMT by Salam Ashour

Am J Clin Pathol. 2021 Aug 31:aqab101. doi: 10.1093/ajcp/aqab101. Online ahead of print.

ABSTRACT

OBJECTIVES: SMARCA4-deficient undifferentiated tumor has distinct clinicopathologic features. We describe our experience with primary diagnosis on adrenal sampling.

METHODS: We collected six SMARCA4-deficient undifferentiated tumors diagnosed on adrenal sampling. Immunostains for SMARCA4, SF-1, inhibin, calretinin, S-100 protein, EMA, and TTF-1 were performed. A control group of 63 primary adrenocortical tumors was also immunostained.

RESULTS: Patients included four men and two women (aged 52-77 years). Five had unilateral adrenal masses and one bilateral (range, 2.4-9.6 cm). Five had pulmonary masses, and one had a midline mediastinal mass. All cases had a monotonous epithelioid appearance and variable rhabdoid morphology. Immunophenotypically, all six cases had loss of nuclear SMARCA4 expression and no staining for SF-1, inhibin, calretinin, or S-100 protein. Variable EMA immunoreactivity was present in four of six cases and focal nuclear TTF-1 expression in one of six. All 63 adrenocortical neoplasms had retained nuclear SMARCA4 expression.

CONCLUSIONS: SMARCA4-deficient undifferentiated tumor may present in the adrenal gland, and this series likely represents metastases from thoracic primaries. Because of the frequent absence of lineage marker expression, knowledge of the characteristic clinical presentation, the rhabdoid morphology, and the typical immunophenotype (loss of SMARCA4/BRG1) allow for appropriate distinction from adrenocortical carcinoma.

PMID:34463317 | DOI:10.1093/ajcp/aqab101

LncRNA expression and SDHB mutations in pheochromocytomas and paragangliomas

Fetched: September 1st, 2021, 5:00am GMT by Huihua Li

Ann Diagn Pathol. 2021 Jul 31;55:151801. doi: 10.1016/j.anndiagpath.2021.151801. Online ahead of print.

ABSTRACT

Although pheochromocytomas and paragangliomas (PPGLs) are usual low-grade neoplasms, the metastatic forms of these lesions are associated with high morbidity and mortality. Recent studies have discovered multiple aberrantly expressed long non-coding RNAs (lncRNAs) in cancers that may have regulatory roles in tumor pathogenesis and metastasis; however, the roles of some lncRNAs in PPGLs are still unknown. The expression levels of lncRNAs including metastasis-associated lung adenocarcinoma transcript (MALAT1), prostate cancer antigen 3 (PCA3), and HOX transcript antisense intergenic RNA (HOTAIR) in PPGLs were analyzed by in situ hybridization, using two tissue microarrays (TMAs). The pheochromocytoma (PCC) TMA consisted of normal adrenal medulla (N = 25), non-metastatic PCCs (N = 76) and metastatic PCCs (N = 5) while the paraganglioma (PGL) TMA had 73 non-metastatic PGLs and 5 metastatic PGLs. Immunohistochemical staining was performed on all samples with an anti-SDHB antibody. The correlations between lncRNA expression, loss of SDHB expression and clinical characteristics including tumor progression and disease prognosis were investigated. The expression levels of MALAT1 and PCA3 were significantly elevated (2.5-3.9 folds) in both non-metastatic and metastatic PCCs compared to normal adrenal medulla, although there were no significant differences between the non-metastatic and metastatic neoplasms. In contrast to non-metastatic PGLs, metastatic PGLs had significantly upregulated expression of MALAT1, PCA3, and HOTAIR. SDHB loss was more frequently observed in PGLs (25 of 78), especially in metastatic PGLs (5 of 5), compared to PCCs (2 of 81) and in 0 of 5 metastatic PCCs. Patients with SDHB loss, in contrast to SDHB retained, were younger at diagnosis, had higher rates of tumor recurrence, metastatic disease, and mortality. In addition, PGLs with SDHB loss had significantly increased expression of PCA3 compared to tumors with intact SDHB expression. Our findings suggest that specific lncRNAs may be involved in the SDHx signaling pathways in the tumorigenesis and in the development of PPGL.

PMID:34461576 | DOI:10.1016/j.anndiagpath.2021.151801

Permalink for 'A first report of a rare TP53 variant associated with Li-Fraumeni syndrome manifesting as invasive breast cancer and malignant solitary fibrous tumor'

A first report of a rare TP53 variant associated with Li-Fraumeni syndrome manifesting as invasive breast cancer and malignant solitary fibrous tumor

Fetched: September 1st, 2021, 5:00am GMT by Juraj Prejac

World J Surg Oncol. 2021 Aug 27;19(1):254. doi: 10.1186/s12957-021-02370-8.

ABSTRACT

BACKGROUND: Li-Fraumeni is a rare autosomal dominant cancer predisposition syndrome. The basis is a germline mutation of TP53 gene which encodes tumor suppressor protein resulting in early onset of tumors, most often breast cancer, soft tissue sarcomas, brain tumors, adrenocortical carcinomas, and leukemia.

CASE REPORT: We present a case of a young woman with a positive family history for cancer diagnosed with malignant solitary fibrous tumor and luminal B-like invasive breast cancer. Breast cancer and sarcomas account for the majority of tumors associated with Li-Fraumeni syndrome, yet solitary fibrous tumor is a rare clinical entity with no established guidelines for treatment. Even though both primary tumors were successfully resected, the sarcoma relapsed in the form of lung metastases. The NGS analysis revealed single nucleotide variant (c.1101-1G>A) in TP53 gene, affecting the acceptor splice site at intron 10. Until now, only one case of this genetic variant has been documented with conflicting interpretations of pathogenicity.

CONCLUSIONS: The knowledge of TP53 mutation status is essential since the management of these patients requires different approach to avoid excessive toxicity due to the risk of developing secondary malignancy. Using the clinical criteria to screen for affected individuals facilitates appropriate early genetic counseling of patients and their families. Following the American College of Medical Genetics criteria, we believe that the reported single nucleotide variant (c.1101-1G>A) in TP53 gene should be considered pathogenic.

PMID:34452612 | PMC:PMC8399826 | DOI:10.1186/s12957-021-02370-8

Nivolumab induced hypophysitis in a patient with recurrent non-small cell lung cancer

Fetched: August 31st, 2021, 5:00am GMT by Smile Kajal

Drug Discov Ther. 2021 Aug 29. doi: 10.5582/ddt.2021.01006. Online ahead of print.

ABSTRACT

Nivolumab is a programmed death receptor-1 blocking monoclonal antibody which has been approved by United States Food and Drug Administration for patients with metastatic non-squamous non-small cell lung cancer. Endocrinopathies like thyroid dysfunction and adrenal insufficiency are its known immune related adverse effects. Hypophysitis is very rare and usually presents with minimal symptoms. We report development of hypophysitis in an 84-year-old female patient who developed a range of symptoms (fatigue, headache, nausea) as well as laboratory confirmation of both central hypothyroidism and central adrenal deficiency which is unusual in cases of nivolumab induced hypophysitis. The patient had well differentiated adenocarcinoma of the left upper lobe of the lung. She underwent wedge resection followed by chemotherapy and was started on nivolumab due to recurrence. After 14 cycles of nivolumab, she started complaining of intense fatigue. She was found to have central thyroid deficiency and was started on levothyroxine. But her symptoms did not improve. Then she underwent adrenocorticotropic hormone stimulation test which showed central adrenal deficiency, but her brain magnetic resonance imaging did not reveal any pituitary or sellar changes. A diagnosis of nivolumab induced hypophysitis was made, based on clinical grounds and hormonal profile and she was started on oral steroids. She responded dramatically to this steroidal therapy within four weeks of its initiation and her immunotherapy with nivolumab was restarted.

PMID:34456195 | DOI:10.5582/ddt.2021.01006

Permalink for 'International initiative for a curated SDHB variant database improving the diagnosis of hereditary paraganglioma and pheochromocytoma'

International initiative for a curated SDHB variant database improving the diagnosis of hereditary paraganglioma and pheochromocytoma

Fetched: August 29th, 2021, 5:00am GMT by Laurene Ben Aim

J Med Genet. 2021 Aug 27:jmedgenet-2020-107652. doi: 10.1136/jmedgenet-2020-107652. Online ahead of print.

ABSTRACT

BACKGROUND: SDHB is one of the major genes predisposing to paraganglioma/pheochromocytoma (PPGL). Identifying pathogenic SDHB variants in patients with PPGL is essential to the management of patients and relatives due to the increased risk of recurrences, metastases and the emergence of non-PPGL tumours. In this context, the 'NGS and PPGL (NGSnPPGL) Study Group' initiated an international effort to collect, annotate and classify SDHB variants and to provide an accurate, expert-curated and freely available SDHB variant database.

METHODS: A total of 223 distinct SDHB variants from 737 patients were collected worldwide. Using multiple criteria, each variant was first classified according to a 5-tier grouping based on American College of Medical Genetics and NGSnPPGL standardised recommendations and was then manually reviewed by a panel of experts in the field.

RESULTS: This multistep process resulted in 23 benign/likely benign, 149 pathogenic/likely pathogenic variants and 51 variants of unknown significance (VUS). Expert curation reduced by half the number of variants initially classified as VUS. Variant classifications are publicly accessible via the Leiden Open Variation Database system [https:]

CONCLUSION: This international initiative by a panel of experts allowed us to establish a consensus classification for 223 SDHB variants that should be used as a routine tool by geneticists in charge of PPGL laboratory diagnosis. This accurate classification of SDHB genetic variants will help to clarify the diagnosis of hereditary PPGL and to improve the clinical care of patients and relatives with PPGL.

PMID:34452955 | DOI:10.1136/jmedgenet-2020-107652

Assessment of the AJCC staging system of pheochromocytomas/paragangliomas

Fetched: August 29th, 2021, 5:00am GMT by Omar Abdel-Rahman

Endocrine. 2021 Aug 27. doi: 10.1007/s12020-021-02854-3. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aims to assess the performance of the AJCC 8th staging system for pheochromocytomas and paragangliomas (PPGLs) based on a population-based cohort.

METHODS: Surveillance, epidemiology, and end results (SEER)-18 registry database was reviewed, and patients with PPGLs diagnosed 2004-2015 were reviewed. AJCC stage for each patient was reconstructed from the collaborative stage dataset. Kaplan-Meier survival estimates according to the AJCC stage were reviewed, and multivariable Cox regression analysis was conducted to determine the impact of AJCC stages on overall and cancer-specific survival.

RESULTS: A total of 416 patients with PPGLs were eligible and were included in the current analysis. Using Kaplan-Meier survival estimates, patients with stage IV seem to have the worst overall survival (P < 0.001). When the results were stratified by the site of origin (adrenal vs. extra-adrenal), similar findings were observed in both strata (P < 0.001 in each stratum). Using multivariable Cox regression analysis for overall survival, HR for stage I vs. II was: 0.59; (95% CI: 0.27-1.27), HR for stage II vs. III: 0.82; (95% CI: 0.41-1.63), and HR for stage III vs. IV was: 0.37; (95% CI: 0.24-0.58). Likewise, for cancer-specific survival, HR for stage I vs. II was: 0.72; (95% CI: 0.26-1.97), HR for stage II vs. III: 0.64; (95% CI: 0.25-1.63), and HR for stage III vs. IV was: 0.33; (95% CI: 0.19-0.56). C-statistic for AJCC 8th staging system was: 0.723 (95% CI: 0.669-0.776).

CONCLUSION: Further improvements within AJCC 8th edition are possible, including the inclusion of the extent of metastatic disease in the subclassification of stage IV disease, and not considering primary tumor site when assigning T stage.

PMID:34449032 | DOI:10.1007/s12020-021-02854-3

Obesity, height, and serum androgen metabolism among postmenopausal women in the Women's Health Initiative Observational Study

Fetched: August 29th, 2021, 5:00am GMT by Hannah Oh

Cancer Epidemiol Biomarkers Prev. 2021 Aug 26:cebp.0604.2021. doi: 10.1158/1055-9965.EPI-21-0604. Online ahead of print.

ABSTRACT

BACKGROUND: Anthropometric measures, including obesity, are important risk factors for breast and endometrial cancers in postmenopausal women. It is unknown whether these risk factors are associated with androgen metabolism, another risk factor for these cancers.

METHODS: Using baseline data from 1,765 postmenopausal women in the Women's Health Initiative Observational Study, we conducted a cross-sectional analysis examining associations between anthropometric measures (current body mass index [BMI], waist-to-hip ratio [WHR], height, and recalled BMI at age 18) and serum androgen metabolites. Twelve androgens/androgen metabolites were quantified using liquid chromatography-tandem mass spectrometry. Geometric means of androgen/androgen metabolite concentrations were estimated using linear regression, adjusting for potential confounders and stratified by hormone therapy (HT) use.

RESULTS: Regardless of HT use, higher current BMI (>30 vs. <25 kg/m2) was associated with higher serum concentrations of DHEAS, 5α-reduced glucuronide metabolites (ADT-G, 3α-diol-3G, 3α-diol-17G), and DHEAS:DHEA ratio (all p-trend<0.02). BMI was also positively associated with unconjugated estrone:androstenedione and unconjugated estradiol:testosterone ratios among never/former HT users (all p-trend<0.001) but not in current users (p-int<0.001). WHR was positively associated with adrenal androgens and 5α-reduced glucuronide metabolites in obese women only (BMI>30 kg/m2; all p-trend<0.01). BMI at age 18 was inversely associated with adrenal androgens (DHEA, DHEAS, androstenedione, testosterone) and 5α-reduced glucuronide metabolites in never/former HT users (all p-trend<0.06). Height was not associated with androgen metabolites.

CONCLUSIONS: Current BMI is associated with androgen metabolism among postmenopausal women.

IMPACT: This study contributes to our understanding of the link between obesity and cancer risk in postmenopausal women.

PMID:34446472 | DOI:10.1158/1055-9965.EPI-21-0604

Permalink for 'Effect of Systemic Steroid Use for Immune-Related Adverse Events in Patients with Non-Small Cell Lung Cancer Receiving PD-1 Blockade Drugs'

Effect of Systemic Steroid Use for Immune-Related Adverse Events in Patients with Non-Small Cell Lung Cancer Receiving PD-1 Blockade Drugs

Fetched: August 29th, 2021, 5:00am GMT by Atsuto Mouri

J Clin Med. 2021 Aug 23;10(16):3744. doi: 10.3390/jcm10163744.

ABSTRACT

OBJECTIVES: Programmed death-1(PD-1)/programmed death ligand-1 (PD-L1) antibodies have clinical benefits for cancer patients facing immune-related adverse events (irAEs). However, the effect of steroid use on the prognosis of patients with non-small cell lung cancer (NSCLC) receiving PD-1 blockade remains unclear.

METHODS: NSCLC patients with complete response (CR)/partial response (PR) or stable disease (SD)/not evaluable (NE) status plus progression-free survival (PFS) of 180 days after PD-1 blockade from December 2015 to December 2018 were retrospectively registered in our study and were divided into two groups: those with and without systemic steroid use for irAEs.

RESULTS: In total, 126 patients who had benefitted from PD-1 blockade were enrolled in our study; among them, 44 received systemic steroids for irAEs, and 82 had no adverse events or, if they did, did not receive systemic steroids. Among the 44 patients requiring steroids, interstitial lung disease (ILD), adrenal insufficiency, diarrhea, and liver dysfunction were observed in 19, 9, 4, and 4 patients, respectively. More side effects were observed in the group treated by steroids. The median PFS and overall survival (OS) in patients with and without systemic steroid use were 11.7 and 16.0 months (p < 0.037) and 35.0 and 41.0 months (p < 0.28), respectively. In univariate and multivariate analyses of survival, systemic steroid treatment for irAEs was significantly associated with PFS. The occurrence of ILD, adrenal insufficiency, and fever was significant in patients who used systemic steroids for irAEs.

CONCLUSIONS: Patients administered systemic steroids for irAEs due to PD-1 blockade treatment exhibited shorter PFS than those who were not. Systemic steroids might affect survival after PD-1 blockade even for patients who once acquired its clinical benefit.

PMID:34442054 | PMC:PMC8397225 | DOI:10.3390/jcm10163744

Surgical Management of Adrenocortical Carcinoma: Current Highlights

Fetched: August 29th, 2021, 5:00am GMT by Giuseppe Cavallaro

Biomedicines. 2021 Jul 28;9(8):909. doi: 10.3390/biomedicines9080909.

ABSTRACT

INTRODUCTION: Adrenocortical carcinoma (ACC) is a rare tumor, often discovered at an advanced stage and associated with poor prognosis. Treatment is guided by staging according to the European Network for the Study of Adrenal Tumors (ENSAT) classification. Surgery is the treatment of choice for ACC. The aim of this review is to provide a complete overview on surgical approaches and management of adrenocortical carcinoma.

METHODS: This comprehensive review has been carried out according to the PRISMA statement. The literature sources were the databases PubMed, Scopus and Cochrane Library. The search thread was: ((surgery) OR (adrenalectomy)) AND (adrenocortical carcinoma).

RESULTS: Among all studies identified, 17 were selected for the review. All of them were retrospective. A total of 2498 patients were included in the studies, of whom 734 were treated by mini-invasive approaches and 1764 patients were treated by open surgery.

CONCLUSIONS: Surgery is the treatment of choice for ACC. Open adrenalectomy (OA) is defined as the gold standard. In recent years laparoscopic adrenalectomy (LA) has gained more popularity. No significant differences were reported for overall recurrence rate, time to recurrence, and cancer-specific mortality between LA and OA, in particular for Stage I-II. Robotic adrenalectomy (RA) has several advantages compared to LA, but there is still a lack of specific documentation on RA use in ACC.

PMID:34440112 | PMC:PMC8389566 | DOI:10.3390/biomedicines9080909

Permalink for 'Molecular Mechanisms of Functional Adrenocortical Adenoma and Carcinoma: Genetic Characterization and Intracellular Signaling Pathway'

Molecular Mechanisms of Functional Adrenocortical Adenoma and Carcinoma: Genetic Characterization and Intracellular Signaling Pathway

Fetched: August 29th, 2021, 5:00am GMT by Hiroki Shimada

Biomedicines. 2021 Jul 26;9(8):892. doi: 10.3390/biomedicines9080892.

ABSTRACT

The adrenal cortex produces steroid hormones as adrenocortical hormones in the body, secreting mineralocorticoids, glucocorticoids, and adrenal androgens, which are all considered essential for life. Adrenocortical tumors harbor divergent hormonal activity, frequently with steroid excess, and disrupt homeostasis of the body. Aldosterone-producing adenomas (APAs) cause primary aldosteronism (PA), and cortisol-producing adenomas (CPAs) are the primary cause of Cushing's syndrome. In addition, adrenocortical carcinoma (ACC) is a highly malignant cancer harboring poor prognosis. Various genetic abnormalities have been reported, which are associated with possible pathogenesis by the alteration of intracellular signaling and activation of transcription factors. In particular, somatic mutations in APAs have been detected in genes encoding membrane proteins, especially ion channels, resulting in hypersecretion of aldosterone due to activation of intracellular calcium signaling. In addition, somatic mutations have been detected in those encoding cAMP-PKA signaling-related factors, resulting in hypersecretion of cortisol due to its driven status in CPAs. In ACC, mutations in tumor suppressor genes and Wnt-β-catenin signaling-related factors have been implicated in its pathogenesis. In this article, we review recent findings on the genetic characteristics and regulation of intracellular signaling and transcription factors in individual tumors.

PMID:34440096 | PMC:PMC8389593 | DOI:10.3390/biomedicines9080892

Real-world efficacy of osimertinib in previously EGFR-TKI treated NSCLC patients without identification of T790M mutation

Fetched: August 27th, 2021, 5:00am GMT by Yung-Hung Luo

J Cancer Res Clin Oncol. 2021 Aug 26. doi: 10.1007/s00432-021-03766-5. Online ahead of print.

ABSTRACT

BACKGROUND: The efficacy of osimertinib in previously EGFR-TKI-treated NSCLC without identification of T790M mutational status remains unclear in real-world practice.

PATIENTS AND METHODS: 417 patients had stage III-IV NSCLC harboring EGFR mutation and 154 out of 417 patients receiving osimertinib as ≥ second-line EGFR-TKI were identified. The time to treatment failure and risk of death were analyzed.

RESULTS: Higher risk of death was found in EGFR-mutant patients with age ≥ 65 years, non-adenocarcinoma, no surgery or radiation, non-exon 19 deletion/exon 21 L858R, higher ECOG PS (2-4), PD-L1 expression ≥ 50%, and bone/liver/adrenal metastasis (all p < 0.05). Osimertinib as ≥ second-line TKI in patients with/without identification of T790M revealed lower risk of death compared to first-line first/second generation TKI without subsequent osimertinib (p = 0.0002; 0.0232, respectively). However, osimertinib-treated patients with T790M did not have superior survival than those without (p = 0.2803). A higher risk of treatment failure for osimertinib was found in males, patients with first-line TKI duration ≤ 12 months, BMI drop > 10%, and PD-L1 expression ≥ 50% (All p < 0.05). Nonetheless, osimertinib as ≥ second-line TKI in patients without identification of 790 M did not have higher risk of treatment failure than those with T790M (p = 0.1236).

CONCLUSIONS: This study demonstrates that osimertinib as second line or subsequent TKI in EGFR-TKI-treated patients without identification of T790M revealed lower risk of death compared to first-line first/second generation TKI without subsequent osimertinib, in real-world practice. Additionally, EGFR-mutant patients with PD-L1 expression ≥ 50% had a higher risk of treatment failure for osimertinib and worse overall survival than those with PD-L1 expression < 50%. These results suggest that osimertinib as second line or subsequent TKI may be a potential alternative option for the treatment of patients without identification of T790M and PD-L1 expression ≥ 50% is associated with a significantly poor outcome in patients receiving osimertinib.

PMID:34436667 | DOI:10.1007/s00432-021-03766-5

Spontaneous rupture of adrenal myelolipoma as a cause of acute flank pain: A case report

Fetched: August 27th, 2021, 5:00am GMT by Dong Soo Kim

World J Clin Cases. 2021 Aug 6;9(22):6552-6556. doi: 10.12998/wjcc.v9.i22.6552.

ABSTRACT

BACKGROUND: Adrenal myelolipoma is a rare, benign, non-functioning mass that occurs in the adrenal gland. It is composed of an admixture of hematopoietic elements and mature adipose tissue, similar to bone marrow. Even at large sizes, adrenal myelolipomas are usually asymptomatic and often incidentally found by ultrasonography or computed tomography (CT) scan. This paper describes an unusual case of adrenal myelolipoma presenting as flank pain.

CASE SUMMARY: A 50-year-old male with severe right flank pain underwent a CT scan revealing a huge mass extending into the suprarenal space. The mass showed a fat component with retroperitoneal hemorrhage. The tumor was treated laparoscopically, and pathologic examination revealed features of myelolipoma originating from the adrenal gland.

CONCLUSION: Adrenal myelolipomas are generally asymptomatic and can be treated conservatively. However, rupture and hemorrhage of the tumor can cause symptoms requiring surgical removal.

PMID:34435025 | PMC:PMC8362562 | DOI:10.12998/wjcc.v9.i22.6552

Bilateral adrenal metastases of endometrial cancer with adrenal insufficiency

Fetched: August 26th, 2021, 5:00am GMT by Tetsuro Shiraishi

J Obstet Gynaecol Res. 2021 Aug 25. doi: 10.1111/jog.14998. Online ahead of print.

ABSTRACT

Adrenal metastasis from endometrial cancer is extremely rare and has a poor prognosis, especially for bilateral adrenal metastases. It is usually asymptomatic without any adrenal hormonal abnormalities. A 50-year-old postmenopausal woman presented with acute right-sided back pain and history of occasional abnormal uterine bleeding. She was diagnosed with endometrial cancer with ruptured bilateral adrenal metastases. She underwent total hysterectomy and bilateral salpingo-oophorectomy, and the pathological findings revealed dedifferentiated carcinoma. After three courses of adjuvant chemotherapy, the bilateral adrenal metastases had increased in size, with worsening back pain and adrenal hormone insufficiency. The patient died 6 months after the identification of adrenal tumors. Acute back pain may lead to the identification of a ruptured adrenal metastasis. The possibility of gradual adrenal insufficiency should be considered in bilateral adrenal metastases. Although the prognosis is poor, tumor debulking surgery followed by adjuvant chemotherapy could be suggested to improve the prognosis.

PMID:34433231 | DOI:10.1111/jog.14998

Permalink for 'Adrenal crisis and acute exacerbation of interstitial lung disease after thymoma needle biopsy: a case report and literature review'

Adrenal crisis and acute exacerbation of interstitial lung disease after thymoma needle biopsy: a case report and literature review

Fetched: August 26th, 2021, 5:00am GMT by Hengyi Yan

Transl Lung Cancer Res. 2021 Jul;10(7):3292-3302. doi: 10.21037/tlcr-21-195.

ABSTRACT

Thymoma is the most common paraneoplastic syndrome-associated tumor. It is related to a variety of autoimmune diseases including myasthenia gravis, systemic lupus erythematosus, and hypogammaglobulinemia. Only a few reports of thymoma associated with Addison's disease have been reported to date. Herein, we report a novel case of thymoma complicated with autoimmune Addison's disease and interstitial lung disease. The patient developed adrenal crisis with persistent hypotensive shock and heart block after needle biopsy. Acute exacerbation of the interstitial lung disease was also observed, accompanied by severe respiratory failure. After treatment with glucocorticoids, somatostatin, and temporary pacemaker implantation, the patient's condition improved, and the thymoma had shrunk in size. Finally, he underwent transsternal extended thymectomy and lymph node dissection. Hydrocortisone was given intravenously before surgery, on the operation day and after the surgery. The operation was uneventful, and no hypotension or fever occurred. Cortisol and ACTH were still obviously abnormal at 1 month post-surgery. The clinical manifestations of Addison's disease and interstitial lung disease are hidden and can be easily overlooked. However, in the postoperative period, Addison's disease can lead to adrenal crisis developing, which can progress to life-threatening shock, arrhythmia, and acute respiratory failure. Therefore, clinicians should be aware of this phenomenon and consider a regimen combining proactive glucocorticoid replacement therapy with somatostatin to preserve the life of such patients.

PMID:34430365 | PMC:PMC8350080 | DOI:10.21037/tlcr-21-195

Thyroid-like follicular carcinoma of kidney: Case presentation and literature review

Fetched: August 25th, 2021, 5:00am GMT by Ameer Afzal

J Pak Med Assoc. 2021 Aug;71(8):2073-2076. doi: 10.47391/JPMA.086.

ABSTRACT

Thyroid follicular carcinoma like renal tumour (TFCLRT) is a rare variant of primary renal epithelial tumour and was first reported in 2006. Up till now, 40 cases have been identified worldwide and alarmingly, 17 cases have been identified from China only. The condition has been included in the WHO Renal Tumours Classification 2016. We present here the first case of thyroid follicular carcinoma like renal tumour from Pakistan that was managed in our surgical unit and a literature review. Left-sided radical nephrectomy was performed through a midline incision. The left kidney was removed along with intact Gerota fascia, left adrenal gland and lymph nodes alongwith aorta.

PMID:34418033 | DOI:10.47391/JPMA.086

Update on Pancreatic Transplantation in the Management of Diabetes

Fetched: August 25th, 2021, 5:00am GMT by Carlo Lombardo

2021 Aug 17. 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

Pancreas transplantation is the most effective therapeutic option that can restore insulin independence in beta-cell penic recipients with diabetes. Because of life-long immunosuppression and the initial surgical risk, pancreas transplantation is a therapeutic option only in selected patients with diabetes. Based on renal function, candidates for pancreas transplantation can be classified into three categories: uremic patients, post-uremic patients (following a successful kidney transplantation), and non-uremic patients. Uremic patients are best treated by a simultaneous kidney-pancreas transplantation. Post-uremic patients can receive a pancreas after kidney transplantation. Non-uremic patients can receive a pancreas transplant alone, if diabetes is poorly controlled resulting in hypoglycemia unawareness, and in the presence of evolving chronic complications of diabetes. Results of pancreas transplantation have improved over time and are currently non-inferior to those of renal transplantation alone in recipients without diabetes. A functioning pancreatic graft can prolong patient survival, dramatically improves quality of life of recipients, and may ameliorate the course of chronic complications of diabetes. Unfortunately, because of ageing of the donor population and lack of timely referral of potential recipients, the annual volume of pancreas transplants is declining. Considering that the results of pancreas transplantation depend on center volume, and that adequate center volume is required also for training of newer generations of transplant surgeons, centralization of pancreas transplantation activity should be considered. The recent world consensus conference on pancreas transplantation provides an independent appraisal of the impact of pancreas transplantation on modern management of diabetes as well as expert guidelines for the practice of pancreas transplantation. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:25905213 | Bookshelf:NBK278979

Hypopituitarism Following Cranial Radiotherapy

Fetched: August 25th, 2021, 5:00am GMT by Sandra Pekic

2021 Aug 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

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

PMID:30321012 | Bookshelf:NBK532082

Hyperthyroidism in Aging

Fetched: August 25th, 2021, 5:00am GMT by Mary H. Samuels

ABSTRACT

Hyperthyroidism in the elderly is a serious clinical condition that is associated with significant morbidity. It may be difficult to diagnose due to the confounding effects of drugs and acute or chronic illnesses on the interpretation of thyroid function tests. In addition, there is a relative paucity of typical hyperadrenergic symptoms in older patients with hyperthyroidism, who instead may present with unexplained weight loss, neurocognitive changes, or cardiovascular effects. Of particular concern is the elevated risk of atrial fibrillation and cardiovascular complications in this age group. There is increasing evidence that even mild (subclinical) hyperthyroidism in the elderly is associated with these risks. Graves’ Disease and toxic multinodular goiter are the most common etiologies of hyperthyroidism in the elderly, although other causes of hyperthyroidism also occur. The use of amiodarone or administration of iodinated contrast agents can also lead to hyperthyroidism, and are commonly prescribed to older patients. Radioiodine or thionamide therapy are typically used to treat hyperthyroidism in older patients. Treatment decisions must be individualized, taking into account projected lifespan, comorbidities, and side effects of therapy. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:25905220 | Bookshelf:NBK278986

Assessing Insulin Sensitivity and Resistance in Humans

Fetched: August 25th, 2021, 5:00am GMT by Ranganath Muniyappa

ABSTRACT

In this chapter we discuss a representative variety of methods currently available for estimating insulin sensitivity/resistance. These range from complex, time consuming, labor-intensive, invasive procedures to simple tests involving a single fasting blood sample. It is important to understand the physiological concepts informing each method so that relative merits and limitations of particular approaches are appropriately matched with proposed applications and data is interpreted correctly. The glucose clamp method is the reference standard for direct measurement of insulin sensitivity. Regarding simple surrogates, QUICKI and Log (HOMA) are among the best and most extensively validated. Dynamic tests are useful if information about both insulin secretion and insulin action are needed.

For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:25905189 | Bookshelf:NBK278954

Hypertension in Diabetes

Fetched: August 25th, 2021, 5:00am GMT by Sowjanya Naha

2021 Aug 7. 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 coexistence of diabetes and hypertension is known to have a multiplicative effect on adverse clinical outcomes with respect to both microvascular and macrovascular disease. Effective management of diabetes should therefore include a multifaceted approach combining optimal control of blood pressure and lipids with appropriate glycemic control. The pathophysiology of hypertension in diabetes involves maladaptive changes in the autonomic nervous system, vascular endothelial dysfunction, enhanced activation of the renin-angiotensin-aldosterone system, immune function alterations, and harmful environmental factors. Multiple high-quality randomized controlled trials have shown improvement in morbidity with lowering of elevated blood pressure in people with diabetes. Attention must be paid to individual risk factors and co-morbidities with a goal of less than 130/80 mm Hg in most patients with diabetes who are at higher risk of cardiovascular disease (CVD) than those without diabetes. Good glycemic control, optimizing weight, and promotion of exercise as well as lessening harmful environment factors such as air pollution exposure are integral components of the approach to blood pressure control in these patients. Judicious selection of therapy and consideration of relevant side-effect profiles is paramount. The potential for both beneficial and detrimental drug interactions must be kept in mind and drug combinations should be chosen after due deliberation. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers remain preferred agents for initiation of antihypertensive therapy, while combined use of these agents is not recommended due to poor renal outcomes. With the advent of newer antidiabetic agents such as SGLT inhibitors and GLP1 receptor agonists, consideration should be given to their antihypertensive, renal, and cardiovascular disease lowering properties when initiating therapy for glycemic control. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:25905256 | Bookshelf:NBK279027

Diffuse Hormonal Systems

Fetched: August 25th, 2021, 5:00am GMT by Amanda Andersson-Rolf

ABSTRACT

Neuroendocrine (NE) cells are rare epithelial cells that, in addition to having an endocrine function, express markers and peptides otherwise associated with neurons and the central nervous system. NE cells can be found as either single cells or small clusters of cells dispersed throughout the parenchymal surface epithelium of different tissues, including the lung, the intestine, and the pancreas. The observation that NE cells, which are dispersed throughout the body in different tissue sites, are often innervated and secrete bioactive compounds that can act both locally and systemically, led to the idea of the diffuse neuroendocrine system, a diffuse hormonal system composed of NE cells. NE cells perform important endocrine functions. Furthermore, NE cells are implicated in several human diseases. In particular, a group of rare tumors that presumably arise from NE cells, neuroendocrine neoplasms (NENs), have sparked a great deal of interest in NE cell biology. NENs can arise in almost all tissues but they show the highest incidence in the lung and the gastroenteropancreatic (GEP) system. In this chapter, we will outline what is currently known about NE cell differentiation and function, focusing specifically on NE cells of the lung, pulmonary neuroendocrine cells (PNECs), and the most prominent NE cells of the GEP system: enteroendocrine cells (EECs) of the small intestine and stomach and pancreatic endocrine cells. We will also discuss the potential role of these specific NE cells in the context of tissue injury. Finally, we will provide a brief overview of NEN biology with regards to NENs arising in the lung and GEP system. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:25905254 | Bookshelf:NBK279025

Pharmacologic Treatment of Overweight and Obesity in Adults

Fetched: August 25th, 2021, 5:00am GMT by Beverly G Tchang

2021 Aug 2. 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

Obesity pharmacotherapy has evolved significantly over the past 60 years. Today, six anti-obesity medications (AOMs) are approved by the Federal Drug Administration (FDA) for the long-term treatment of obesity. Similar in approach to other chronic diseases, AOMs are indicated in combination with lifestyle modification for the management of overweight and obesity. Current guidelines recommend that individuals who have attempted lifestyle improvements and continue to have a body mass index (BMI) of ≥ 30 kg/m² or ≥ 27 kg/m² with an obesity-related comorbidity are eligible for weight loss medication treatment. The AOMs reviewed in this chapter include the FDA-approved medicines for chronic weight management, FDA-approved medicines for short-term use of weight management, and off-label use of medicines that have demonstrated benefits for weight control. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:25905267 | Bookshelf:NBK279038

Permalink for 'Adrenal biopsy, as a diagnostic method, is associated with decreased overall survival in patients with T1/T2 adrenocortical carcinoma: A propensity score-matched analysis'

Adrenal biopsy, as a diagnostic method, is associated with decreased overall survival in patients with T1/T2 adrenocortical carcinoma: A propensity score-matched analysis

Fetched: August 24th, 2021, 5:00am GMT by Samer A Naffouje

J Surg Oncol. 2021 Aug 23. doi: 10.1002/jso.26639. Online ahead of print.

ABSTRACT

INTRODUCTION: The standard diagnosis for adrenocortical carcinoma (ACC) is clinical diagnosis (CD) based on radiographic and biochemical studies. Biopsy diagnosis (BD) is seldom required for the suspicion of secondary malignancy. We aim to study the impact of BD in the context of underlying T1/T2 ACC on overall survival (OS) compared with CD.

METHODS: National Cancer Database (NCDB) for endocrine malignancies was utilized. Only patients with non-metastatic ACC, whose method of diagnosis and local disease extension were reported, and received a surgical adrenalectomy with curative intent were included. Patients were divided by disease stage into T1/T2, T3, and T4 groups. A propensity score match was applied to those with T1/T2 disease who received CD versus BD and the Kaplan-Meier method was used to compare OS.

RESULTS: In total, 4000 patients with ACC were reported in the database, 1410 met selection criteria. Eight hundred and thirty patients had T1/T2, 365 had T3, and 162 had T4 ACC. Of patients with T1/T2 ACC, 742 (89.4%) received CD versus 88 (11.6%) with BD. A propensity score was calculated per a multivariable regression model with 79 patients matched from each group. Exact matching was applied for margin status and adjuvant therapies. Kaplan-Meier analysis showed a significant difference in median OS between CD versus BD patients in the matched data set (103.89 ± 15.65 vs. 54.93 ± 8.22 months; p = 0.001). In all comers, patients with T1/T2 ACC and BD had comparable median OS to that of patients with T3 ACC (52.21 ± 9.69 vs. 36.01 ± 3.33 months; p = 0.446).

CONCLUSION: BD in T1/T2 ACC could be associated with disease upstaging and worse OS outcomes.

PMID:34424540 | DOI:10.1002/jso.26639

Adrenal Incidentaloma. Reply

Fetched: August 24th, 2021, 5:00am GMT by Electron Kebebew

N Engl J Med. 2021 Aug 19;385(8):768. doi: 10.1056/NEJMc2108550.

NO ABSTRACT

PMID:34407359 | DOI:10.1056/NEJMc2108550

Investigation of spleen CXCR4 expression by [(68)Ga]Pentixafor PET in a cohort of 145 solid cancer patients

Fetched: August 22nd, 2021, 5:00am GMT by Richard Lewis

EJNMMI Res. 2021 Aug 21;11(1):77. doi: 10.1186/s13550-021-00822-6.

ABSTRACT

BACKGROUND: The chemokine receptor CXCR4 is frequently overexpressed and associated with adverse prognosis in most hematopoietic malignancies and solid cancers. Recently, CXCR4 molecular imaging using the CXCR4-specific positron emission tomography (PET) tracer Pentixafor ([⁶⁸Ga]Pentixafor) has become a well-established method to non-invasively measure CXCR4 expression in vivo. In previous Pentixafor imaging studies, highly variable CXCR4 tracer uptake to the spleen was observed.

RESULTS: We investigated the hypothesis that enhanced spleen [⁶⁸Ga]Pentixafor uptake and thus CXCR4 expression in patients with solid tumors would indicate an activated spleen state and/or an association with clinical and prognostic features and survival parameters. In this retrospective study, [⁶⁸Ga]Pentixafor-PET images and patient records of 145 solid tumor patients representing 27 cancer entities were investigated for an association of spleen [⁶⁸Ga]Pentixafor uptake and clinical characteristics and outcome. Based on this assessment, we did not observe differences in clinical outcomes, measured by progression-free survival, overall survival and remission status neither within the entire cohort nor within subgroups of adrenal cancer, desmoplastic small round cell tumor, neuroendocrine tumors, non-small cell lung cancer, small cell lung cancer and pancreatic adenocarcinoma patients. No tumor entity showed especially high levels of spleen [⁶⁸Ga]Pentixafor uptake compared to others or a control cohort. However, when investigating laboratory parameters, there was a positive correlation of high spleen [⁶⁸Ga]Pentixafor uptake with leukocyte and/or platelet counts in neuroendocrine tumors, non-small cell lung cancer and small cell lung cancer.

CONCLUSION: Spleen [⁶⁸Ga]Pentixafor uptake was not associated with stage of disease and clinical outcomes in solid tumor patients. We identified positively associated platelet and/or leukocyte counts with spleen [⁶⁸Ga]Pentixafor uptake in neuroendocrine tumors, non-small cell lung cancer and small cell lung cancer, suggesting that splenic CXCR4 expression could possibly play a role in systemic immunity/inflammation in some types of solid tumors or a subgroup of patients within solid tumor entities.

PMID:34417915 | PMC:PMC8380222 | DOI:10.1186/s13550-021-00822-6

Permalink for 'Downstaging and Resection of Initially Unresectable Hepatocellular Carcinoma with Tyrosine Kinase Inhibitor and Anti-PD-1 Antibody Combinations'

Downstaging and Resection of Initially Unresectable Hepatocellular Carcinoma with Tyrosine Kinase Inhibitor and Anti-PD-1 Antibody Combinations

Fetched: August 22nd, 2021, 5:00am GMT by Xiao-Dong Zhu

Liver Cancer. 2021 Jul;10(4):320-329. doi: 10.1159/000514313. Epub 2021 Mar 30.

ABSTRACT

BACKGROUND: Combined therapy with tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies has shown high tumor response rates for patients with unresectable hepatocellular carcinoma (HCC). However, using this treatment strategy to convert initially unresectable HCC to resectable HCC was not reported.

METHODS: Consecutive patients with unresectable HCC who received first-line therapy with combined TKI/anti-PD-1 antibodies were analyzed. Tumor response and resectability were evaluated via imaging every 2 months (±2 weeks) using RECIST v1.1. Resectability criteria were (1) R0 resection could be achieved with sufficient remnant liver volume and function; (2) intrahepatic lesions were evaluated as partial responses or stable disease for at least 2 months; (3) no severe or persistent adverse effects occurred; and (4) hepatectomy was not contraindicated.

RESULTS: Sixty-three consecutive patients were enrolled. Of them, 10 (15.9%) underwent R0 resection in 3.2 months (range: 2.4-8.3 months) after the initiation of combination therapy. At baseline, these 10 patients had a median largest tumor diameter of 9.3 cm, 7 had Barcelona Clinic Liver Cancer stage C (vascular invasion) disease, 2 had stage B, and 1 had stage A. Before surgery, 6 patients were evaluated as a partial response, 3 stable disease, and 1 partial response in the intrahepatic lesion but a new metastatic lesion in the right adrenal gland. Six patients (60%) achieved a pathological complete response. One patient died from immune-related adverse effects 2.4 months after hepatectomy. After a median follow-up of 11.2 months (range: 7.8-15.9 months) for other 9 patients, 8 survived without disease recurrence, and 1 experienced tumor recurrence.

CONCLUSIONS: Combination of TKI/anti-PD-1 antibodies is a feasible conversion therapy for patients with unresectable HCC to become resectable. This study represents the largest patient cohort on downstaging role of combinational systemic therapy on TKI and PD-1 antibody for HCC.

PMID:34414120 | PMC:PMC8339461 | DOI:10.1159/000514313

A rare case of synovial sarcoma with lung, heart and adrenal gland metastasis: a caution for patients and clinicians

Fetched: August 22nd, 2021, 5:00am GMT by Lisha Jiang

J Int Med Res. 2021 Aug;49(8):3000605211037839. doi: 10.1177/03000605211037839.

ABSTRACT

A 68-year-old man presented to the Urology Clinic, West China Hospital, Chengdu, with a suspected right adrenal gland mass that had persisted for two months. He had no associated lumbodynia, dizziness or palpitation. Abdominal computed tomography (CT) revealed an uneven density and contrast-enhanced oval-like mass with smooth edges in the right adrenal gland. Laparoscopic right adrenal gland resection followed by histopathology confirmed a diagnosis of metastatic synovial sarcoma. The patient had a history of synovial sarcoma on the right upper leg 3 years previously that was surgically treated, but he had not undergone further treatment. Approximately 1.5 years later, he had undergone surgery for heart and lung metastasis from the synovial sarcoma of the thigh. At 5 months following laparoscopic right adrenal gland resection, abdominal CT showed a significant sign of right adrenal recurrence, and targeted therapy of 12 mg oral anlotinib, daily, was initiated. This relatively rare but alarming case highlights the importance of patient understanding and compliance to treatment.

PMID:34407686 | PMC:PMC8381427 | DOI:10.1177/03000605211037839

Adrenal Metastasis

Fetched: August 20th, 2021, 5:00am GMT by Shashank R. Cingam

2021 Aug 11. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan–.

ABSTRACT

Adrenal metastases are the most common malignant lesions involving the adrenal gland and the second most common tumor of the adrenal gland after benign adenomas. These metastases were primarily found on autopsy. However, with the increasing role of CT, MRI, and PET in diagnosing, staging, and follow-up of malignancies, adrenal metastases are increasingly found incidentally.

PMID:28722909 | Bookshelf:NBK441879

The prevalence of inorganic mercury in human cells increases during aging but decreases in the very old

Fetched: August 20th, 2021, 5:00am GMT by Roger Pamphlett

Sci Rep. 2021 Aug 18;11(1):16714. doi: 10.1038/s41598-021-96359-8.

ABSTRACT

Successful aging is likely to involve both genetic and environmental factors, but environmental toxicants that accelerate aging are not known. Human exposure to mercury is common, and mercury has genotoxic, autoimmune, and free radical effects which could contribute to age-related disorders. The presence of inorganic mercury was therefore assessed in the organs of 170 people aged 1-104 years to determine the prevalence of mercury in human tissues at different ages. Mercury was found commonly in cells of the brain, kidney, thyroid, anterior pituitary, adrenal medulla and pancreas. The prevalence of mercury in these organs increased during aging but decreased in people aged over 80 years. People with mercury in one organ usually also had mercury in several others. In conclusion, the prevalence of inorganic mercury in human organs increases with age. The relative lack of tissue mercury in the very old could account for the flattened mortality rate and reduced incidence of cancer in this advanced age group. Since mercury may accelerate aging, efforts to reduce atmospheric mercury pollution could improve the chances of future successful aging.

PMID:34408264 | PMC:PMC8373952 | DOI:10.1038/s41598-021-96359-8

Permalink for 'Circulating and intra-tumoral adrenal androgens correlate with response to abiraterone in men with castration resistant prostate cancer'

Circulating and intra-tumoral adrenal androgens correlate with response to abiraterone in men with castration resistant prostate cancer

Fetched: August 20th, 2021, 5:00am GMT by Elahe A Mostaghel

Clin Cancer Res. 2021 Aug 18:clincanres.1819.2021. doi: 10.1158/1078-0432.CCR-21-1819. Online ahead of print.

ABSTRACT

PURPOSE: In metastatic castration resistant prostate cancer (mCRPC) low serum androgens prior to starting Abiraterone Acetate (AA) is associated with more rapid progression. We evaluated the effect of AA on androgens in CRPC metastases and associations of intratumoral androgens with response.

EXPERIMENTAL DESIGN: We performed a phase II study of AA plus prednisone in mCRPC. The primary outcome was tissue testosterone at 4 weeks. Exploratory outcomes were association of steroid levels and genomic alterations with response, and escalating AA to 2000mg at progression.

RESULTS: 29 of 30 men were evaluable. Testosterone in metastatic biopsies became undetectable at 4 weeks (p<0.001). Serum and tissue DHEAS remained detectable in many patients and was not increased at progression. Serum and tissue DHEAS in the lowest quartile (pre-treatment), serum DHEAS in the lowest quartile (4 weeks), and undetectable tissue DHEAS (on therapy) associated with rapid progression (20 vs 48 weeks p=0.0018; 20 vs 52 weeks p=0.0003; 14 vs 40 weeks p=0.0001; 20 vs 56 weeks p=0.02, respectively). One of 16 men escalating to 2000mg had a 30% PSA decline; 13 developed radiographic progression by 12 weeks. Among patients with high serum DHEAS at baseline, wild type PTEN status associated with longer response (61 vs 33 weeks; p=0.02).

CONCLUSION: Low circulating adrenal androgens levels are strongly associated with an androgen-poor tumor microenvironment and with poor response to AA. CRPC patients with higher serum DHEAS levels may benefit from dual-AR pathway inhibition, while those in the lowest quartile may require combinations with non-AR directed therapy.

PMID:34407973 | DOI:10.1158/1078-0432.CCR-21-1819

Adrenal Incidentaloma

Fetched: August 19th, 2021, 5:00am GMT by Haya H Suradi

N Engl J Med. 2021 Aug 19;385(8):768. doi: 10.1056/NEJMc2108550.

NO ABSTRACT

PMID:34407358 | DOI:10.1056/NEJMc2108550

Analysis of absorbed dose in radioimmunotherapy with 177Lu-trastuzumab using two different imaging scenarios: a pilot study

Fetched: August 19th, 2021, 5:00am GMT by Amit Nautiyal

Nucl Med Commun. 2021 Aug 17. doi: 10.1097/MNM.0000000000001472. Online ahead of print.

ABSTRACT

OBJECTIVES: Internal organ dosimetry is an important procedure to demonstrate the reliable application of 177Lu-trastuzumab radioimmunotherapy for human epidermal growth factor receptor-positive metastatic breast cancers. We are reporting the first human dosimetry study for 177Lu-trastuzumab. Another objective of our study was to calculate and compare the absorbed doses for normal organs and tumor lesions in patients before radioimmunotherapy with 177Lu-trastuzumab using two different imaging scenarios.

METHODS: Eleven patients (48.27 ± 8.95 years) with a history of metastatic breast cancer were included in the study. Postadministration of 177Lu-trastuzumab (351.09 ± 23.89 MBq/2 mg), acquisition was performed using planar and hybrid imaging scenarios at 4, 24, 72 and 168 h. Single-photon emission computed tomography/computed tomography imaging was performed at 72 h postinjection. Acquired images were processed using Dosimetry Toolkit software for the estimation of normalized cumulated activity in organs and tumor lesions. OLINDA/EXM 2.0 software was used for absorbed dose calculation in both scenarios.

RESULTS: Significant difference in normalized cumulated activity and the absorbed dose is noted between two imaging scenarios for the organs and tumor lesions (P < 0.05). Mean absorbed dose (mGy/MBq) estimated from heart, lungs, liver, spleen, kidney, adrenal, pancreas and colon using planar and hybrid scenarios were 0.81 ± 0.19 and 0.63 ± 0.17; 0.75 ± 0.13 and 0.32 ± 0.06; 1.26 ± 0.25 and 1.01 ± 0.17; 0.68 ± 0.22 and 0.53 ± 0.16; 0.91 ± 0.3 and 0.69 ± 0.24; 0.18 ± 0.04 and 0.11 ± 0.02; 0.25 ± 0.22 and 0.09 ± 0.02 and 0.75 ± 0.61 and 0.44 ± 0.28, respectively.

CONCLUSIONS: On the basis of our dosimetric evaluation, we concluded that radioimmunotherapy with 177Lu-trastuzumab is well tolerated to be implemented in routine clinical practice against HER2 positive metastatic breast cancer. Liver is the main critical organ at risk. Hybrid scenario demonstrated significantly lower absorbed doses in organs and tumors compared to the multiplanar method.

PMID:34406146 | DOI:10.1097/MNM.0000000000001472

Biochemically silent phaeochromocytoma presenting with non-specific loin pain

Fetched: August 19th, 2021, 5:00am GMT by Annalisa Montebello

BMJ Case Rep. 2021 Aug 16;14(8):e244258. doi: 10.1136/bcr-2021-244258.

ABSTRACT

A 55-year-old woman presented with a 4-month history of right-sided non-specific loin pain and 6 kg weight loss. A CT scan of the abdomen and pelvis showed an incidental 4.5 cm right-sided adrenal lesion which was not typical of an adrenal adenoma. This was further confirmed on MRI of the adrenals. Biochemical investigations to investigate for a functional adrenal lesion included serum catecholamines and metanephrines, an aldosterone to renin ratio and an overnight dexamethasone suppression test. These were all negative. A laparoscopic adrenalectomy was performed in view of the large size of the lesion. Histology was consistent with a phaeochromocytoma, which confirmed the diagnosis of a non-secreting phaeochromocytoma. Non-secreting phaeochromocytomas are rare and usually found in patients with known genetic mutations. Adrenal lesions not related to any mutations similar to our case are even rarer and reported even less in the literature.

PMID:34400431 | PMC:PMC8370509 | DOI:10.1136/bcr-2021-244258

Strategy of reoperation for pheochromocytoma and paraganglioma

Fetched: August 18th, 2021, 5:00am GMT by L Liu

Beijing Da Xue Xue Bao Yi Xue Ban. 2021 Aug 18;53(4):793-797. doi: 10.19723/j.issn.1671-167X.2021.04.029.

ABSTRACT

OBJECTIVE: To explore the surgical strategy and experience of reoperation for pheochromocytoma and paraganglioma which is very challenging.

METHODS: The clinical data of 7 patients with pheochromocytoma and paraganglioma who underwent reoperation in Department of Urology, Peking University Third Hospital from August 2016 to February 2021 were analyzed retrospectively. There were 4 males and 3 females, with an average age of (44.1±11.5) years (28-60 years), 6 cases on the right side and 1 case on the left side. The causes of the operations included: (1) 2 cases of tumor recurrence after resection; (2) The primary operations failed to completely remove the tumors in 3 cases, because the tumors were large and closely related to blood vessels. (3) Pheochromocytoma and paraganglioma wasn't diagnosed before primary operation, therefore, drug preparation wasn't prepared. Two cases were interrupted by severe blood pressure fluctuations during the primary operations. Imaging evaluation, catecholamine biochemical examination and adequate adrenergic α receptor blockers were administrated in all the cases. The surgical approaches included open transperitoneal surgery in 4 cases, robot-assisted laparoscopy in 1 case and retroperitoneal laparoscopy in 2 cases. The innovative techniques included mobilization of the liver, inferior vena cava transection and anastomosis, and transection of left renal vein.

RESULTS: The average tumor size was (8.0±3.2) cm (3.6-13.9 cm). The median interval between the reoperation and the primary operation was 9 months (IQR: 6, 19 months). The median operation time was 407 min (IQR: 114, 430 min) and the median blood loss was 1 500 mL (IQR: 20, 3 800 mL). Operations of 5 cases were performed successfully, and 1 case failed only by exploration during the operation. One case died perioperatively. There were 5 cases of intraoperative blood transfusion, the median transfusion volume of red blood cells was 800 mL (IQR: 0, 2 000 mL). One case experienced postoperative lymphorrhagia, and recovered after conservative treatment. The renal function was normal in 2 cases after resection and anastomosis of inferior vena cava or transection of left renal vein. The average postoperative hospital stay was (7.2±3.3) d (4-13 d). The median follow-up time of 6 patients was 33.5 months (IQR: 4.8, 48.0 months). The case who failed in the reoperation still survived with tumor and there was no recurrence in the rest of the patients.

CONCLUSION: The reoperation of pheochromocytoma and paraganglioma, which can not be resected in the primary operation or recurred postoperatively, is difficult with high risk of hemorrhage, and there is a risk of failure and perioperative death. Different surgical approaches and strategies need to be adopted based on the different situation.

PMID:34393247 | PMC:PMC8365067 | DOI:10.19723/j.issn.1671-167X.2021.04.029

Alectinib for an Octogenarian Patient with Poor Performance Status and ALK Fusion Gene-Positive Lung Cancer-A Case Report

Fetched: August 18th, 2021, 5:00am GMT by Mitsuhiro Kamiyoshihara

Gan To Kagaku Ryoho. 2021 Aug;48(8):1053-1055.

ABSTRACT

An 89-year-old female who had been clinically diagnosed with primary lung cancer underwent right upper lobectomy and lymph node dissection(ND2a-2). Postoperative pathological staging revealed a stage ⅡA(pT1bN1M0)adenocarcinoma that was negative for an EGFR mutation. Nineteen months after surgery, the patient developed a mediastinal lymph node metastasis, and radiotherapy was prescribed. Thirty-eight months later, she developed new mediastinal/hilar lymph node metastases and was prescribed pemetrexed(500 mg on day 1 of each of 3 weeks)as the first-line therapy. A complete response was evident after 10 courses. However, she developed grade 3 nausea, and pemetrexed was discontinued. During 10 months of follow-up, no new lesion appeared; therefore, follow-up was discontinued. Ninety-three months after surgery, she was referred to our hospital because an abnormal shadow was apparent on chest roentgenography. A thorough examination revealed pleural dissemination, pulmonary metastases, mediastinal/hilar lymph node metastases, an adrenal metastasis, and bone metastases. Although her performance status(PS)was poor(grade 4), as the diagnosis was ALK fusion gene-positive adenocarcinoma, alectinib(600 mg once daily)was commenced as the second-line therapy. Complete response was achieved 14 months later(ie, 108 months after surgery and 89 months after postoperative recurrence). Thus, an octogenarian patient with poor PS and ALK fusion gene-positive adenocarcinoma exhibited a complete response after treatment with alectinib.

PMID:34404075

Permalink for 'Complete response of locally advanced left-sided pancreatic cancer after modified FOLFIRINOX chemotherapy followed by conversion surgery: A case report'

Complete response of locally advanced left-sided pancreatic cancer after modified FOLFIRINOX chemotherapy followed by conversion surgery: A case report

Fetched: August 18th, 2021, 5:00am GMT by Sun Jung Kim

Ann Hepatobiliary Pancreat Surg. 2021 Aug 31;25(3):390-394. doi: 10.14701/ahbps.2021.25.3.390.

ABSTRACT

For years, neoadjuvant chemotherapy for locally advanced pancreatic cancer is being investigated and radical surgical resection with laparoscopic approach is getting up to speed. Pathological complete remission is known as a predictive marker for a good prognosis for various carcinomas. Although there are a few case reports about pathological complete remission, there has been no case report of pathological complete remission resulted from successful extensive resection by laparoscopic surgery after a neoadjuvant modified FOLFIRINOX chemotherapy. A 68-year-old male patient was admitted due to a palpable abdominal mass which turned out to be 16-cm-sized huge locally advanced left-sided pancreatic cancer with possible stomach, left adrenal gland, left kidney, and colon invasion. After administration of 10th modified FOLFIRINOX chemotherapy, the tumor had decreased and he underwent laparoscopic radical distal pancreatectomy with splenectomy, left adrenalectomy, wedge resection of stomach, and segmental resection of transverse colon. Although patient had a postoperative micro-abscess around the colon anastomosis site, he was successfully managed with conservative treatment and discharged on 12 days postoperatively. The final pathology reported complete tumor regression. We hereby emphasize the oncologic significance of neoadjuvant chemotherapy in huge left-sided pancreatic cancer and the potential role of laparoscopic conversion surgery.

PMID:34402441 | PMC:PMC8382870 | DOI:10.14701/ahbps.2021.25.3.390

Adrenal cavernous hemangioma: A case report and literature review

Fetched: August 17th, 2021, 5:00am GMT by W Y Kang

Beijing Da Xue Xue Bao Yi Xue Ban. 2021 Aug 18;53(4):808-810. doi: 10.19723/j.issn.1671-167X.2021.04.032.

ABSTRACT

A 57-year-old male patient was referred to our department with complaints of his right adrenal gland occupancy and hypertension about 6 months. When admitted to the hospital, the blood pressure was about 160/100 mmHg, and the heart rate was 110 beats/min. He was no obvious obesity, acne, abnormal mood, without weakness of limbs, acral numbness, palpitation and headache. He presented with type 2 diabetes for more than 3 years, with oral administration of metformin enteric coated tablets and subcutaneous injection of insulin glargine to control blood glucose, and satisfied with blood glucose control. Enhanced CT showed that: the right adrenal gland showed a kind of oval isodense, slightly hypodense shadow, the edge was clear, lobular change, the size was about 5.8 cm×5.4 cm, uneven density, there were nodular and strip calcification, round lipid containing area and strip low density area, and the CT value of solid part was about 34 HU. Enhanced scan showed heterogeneous nodular enhancement in the solid part of the right adrenal gland, nodular enhancement could be seen inside. The CT values of solid part in arterial phase, venous phase and delayed phase were 45 HU, 50 HU and 81 HU, respectively. Considering from the right adrenal gland, cortical cancer was more likely. No obvious abnormality was found in his endocrine examination. After adequate preoperative preparation, retroperitoneal laparoscopic adrenalectomy was performed under general anesthesia. During the operation, the 6 cm adrenal tumor was closely related to the inferior vena cava and liver, and after careful separation, the tumor was completely removed and normal adrenal tissue was preserved. The operation lasted 180 min and the blood loss was 100 mL, and the blood pressure was stable during and after the operation. There was no obvious complication. The results of pathological examinations were as follows: the size of the tumor was 7.5 cm×6.0 cm×3.5 cm, soft, with intact capsule and grayish-red cystic in section. Pathological diagnosis: (right adrenal gland) cavernous hemangioma, secondary intravascular thrombosis, old hemorrhagic infarction with calcification and ossification. After 6 months of observation, no obvious complications and tumor recurrence were found. In summary, cavernous hemangioma of adrenal gland is a rare histopathological change. Its essence is a malformed vascular mass. Blood retention is the cause of thrombosis and calcification in malformed vessels. The imaging findings were inhomogeneous enhancement of soft tissue masses, and the adrenal function examination showed no obvious abnormalities. Retroperitoneal laparoscopic surgery is feasible after adequate preoperative preparation. It is difficult to diagnose the disease preoperatively and needs to be confirmed by postoperative pathology.

PMID:34393250 | PMC:PMC8365077 | DOI:10.19723/j.issn.1671-167X.2021.04.032

Clinicopathological features and prognosis of fumarate hydratase deficient renal cell carcinoma

Fetched: August 17th, 2021, 5:00am GMT by Y F Yu

Beijing Da Xue Xue Bao Yi Xue Ban. 2021 Aug 18;53(4):640-646. doi: 10.19723/j.issn.1671-167X.2021.04.003.

ABSTRACT

OBJECTIVE: To investigate the clinicopathological features and prognosis of fumarate hydratase deficient renal cell carcinoma (FH-RCC).

METHODS: Immunohistochemical (IHC) staining was used to detect the expression of fumarate hydratase (FH) in tumor tissues of 109 different types of renal cell carcinoma (RCC) patients aged 60 years and younger from the Department of Urology of Peking University First Hospital from January 2013 to December 2019. The clinicopathological data and prognosis of FH-RCC were collected and analyzed.

RESULTS: There were eleven patients with FH-negative expression. Seven were males and four females. The age of onset ranged 16-53 years (mean age: 36.7 years), and four female patients all had a history of uterine leiomyoma. Only one first-degree relative of one patient had renal cancer, and none of the patients had a history or family history of cutaneous leiomyomas. The diameter of the tumor was 2.1-12.0 cm (mean: 8.83 cm). Renal sinus or perirenal fat invasion was seen in nine cases, tumor thrombus in renal vein or inferior vena cava in six cases, lymph node metastasis in seven cases, adrenal gland invasion in four cases and splenic capsule invasion in one case. The cases were initially diagnosed as type Ⅱ papillary RCC (7/49, 14.3%), collecting duct carcinoma (2/9, 22.2%) and unclassified RCC (2/51, 3.9%). Tumor histopathology mostly showed a mixture of different structures, such as papillary, tubular cystic, solid, and so on. The most common histological structures were papillary (9/11, 81.8%) and tubular (8/11, 72.7%). Three cases had sarcomatoid areas. At least focal eosinophilic nucleolus (WHO/grades Ⅲ-Ⅳ) and perinuclear halo could be seen in all cases. Immunohistochemical (IHC) stains of most tumors were negative for CA9, CD10 and CK7. The results of fluorescence in situ hybridization (FISH) showed that there was no translocation or amplification of TFE3 gene in two cases with TFE3 IHC expression. All the patients were followed up for 11-82 months. Mean survival was 24 months. Five cases died of distant metastasis 9-31 months after operation (mean: 19 months), and five of the six patients alive had became metastatic.

CONCLUSION: Morphologically, FH-RCC overlaps with many types cell RCC. A mixture of papillary and tubular cystic arrangement is the most common growth pattern of FH-RCC. At least focally large and obvious eosinophilic nucleoli are an important histological feature of this tumor. The negative expression of FH can help to confirm the diagnosis. Young female RCC patients with uterine leiomyomas should be suspected of FH-RCC. Some FH-RCC cases lack clinical evidence. The suspicion raised by pathologists based on histological characteristics is often the key step to further genetic testing and the final diagnosis of the tumor.

PMID:34393221 | PMC:PMC8365061 | DOI:10.19723/j.issn.1671-167X.2021.04.003

Adrenal ganglioneuroma resected for suspicious malignancy: multicenter review of 25 cases and review of the literature

Fetched: August 14th, 2021, 5:00am GMT by Dorit Esther Zilberman

Ann Surg Treat Res. 2021 Aug;101(2):79-84. doi: 10.4174/astr.2021.101.2.79. Epub 2021 Jul 29.

ABSTRACT

PURPOSE: We reviewed the experience with adrenal ganglioneuroma (AGN) pathologically confirmed following adrenalectomy in medium- to high-volume medical centers.

METHODS: The medical records of all adrenalectomy cases in 4 medical centers between 2006 and 2020 were retrospectively reviewed for demographics, clinical, radiological and laboratory findings, surgical treatment, pathology results, and outcomes.

RESULTS: Twenty-five out of 875 adrenalectomy cases (2.9%) were pathologically confirmed as AGN. Those patients' average age was 40.5 years (range, 4-76 years), 13 (52.0%) were males, and 18 lesions (72.0%) were right-sided. One patient had a family history of neurofibromatosis, and another had a succinate dehydrogenase gene mutation. Abdominal/back pain attributed to mass effect was the most common symptom. All 25 patients underwent abdominal computerized tomography scanning in which the average maximal tumor diameter was 6.61 cm. The mean pre- and postcontrast Hounsfield units (HU) values were 35.2 and 59, respectively; and the mean late-phase HU value was 71.1. Twenty-two patients (88.0%) underwent minimally invasive surgery. The average tumor diameter recorded in the final pathology report was 7 cm. Isolated AGN was diagnosed in 21 cases (84.0%), and the additional components reported for the remaining 4 cases included pheochromocytoma (2), ganglioneuroblastoma (1), and neurofibroma (1). The average follow-up length was 16.8 months (range, 1-136 months), during which there was no recurrence or death.

CONCLUSION: AGN is a rare, slow-growing, large benign tumor with radiological characteristics similar to those seen in malignant tumor. Final diagnosis is established by pathology after surgical resection, preferably minimally invasive, with an overall excellent prognosis.

PMID:34386456 | PMC:PMC8331556 | DOI:10.4174/astr.2021.101.2.79

Permalink for 'Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause'

Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause

Fetched: August 14th, 2021, 5:00am GMT by Junhua Zhou

Nat Genet. 2021 Sep;53(9):1360-1372. doi: 10.1038/s41588-021-00906-y. Epub 2021 Aug 12.

ABSTRACT

Most aldosterone-producing adenomas (APAs) have gain-of-function somatic mutations of ion channels or transporters. However, their frequency in aldosterone-producing cell clusters of normal adrenal gland suggests a requirement for codriver mutations in APAs. Here we identified gain-of-function mutations in both CTNNB1 and GNA11 by whole-exome sequencing of 3/41 APAs. Further sequencing of known CTNNB1-mutant APAs led to a total of 16 of 27 (59%) with a somatic p.Gln209His, p.Gln209Pro or p.Gln209Leu mutation of GNA11 or GNAQ. Solitary GNA11 mutations were found in hyperplastic zona glomerulosa adjacent to double-mutant APAs. Nine of ten patients in our UK/Irish cohort presented in puberty, pregnancy or menopause. Among multiple transcripts upregulated more than tenfold in double-mutant APAs was LHCGR, the receptor for luteinizing or pregnancy hormone (human chorionic gonadotropin). Transfections of adrenocortical cells demonstrated additive effects of GNA11 and CTNNB1 mutations on aldosterone secretion and expression of genes upregulated in double-mutant APAs. In adrenal cortex, GNA11/Q mutations appear clinically silent without a codriver mutation of CTNNB1.

PMID:34385710 | DOI:10.1038/s41588-021-00906-y

Permalink for 'A prospective trial demonstrating the benefit of personalized selection of breath-hold technique for upper-abdominal radiotherapy using the Active Breathing Co-ordinator (ABC)'

A prospective trial demonstrating the benefit of personalized selection of breath-hold technique for upper-abdominal radiotherapy using the Active Breathing Co-ordinator (ABC)

Fetched: August 14th, 2021, 5:00am GMT by Briana Farrugia

Int J Radiat Oncol Biol Phys. 2021 Aug 9:S0360-3016(21)02639-0. doi: 10.1016/j.ijrobp.2021.08.001. Online ahead of print.

ABSTRACT

BACKGROUND: For upper abdominal (UA) tumors, our institutional-standard motion reduction method is Expiration Breath Hold (EBH), using Active Breathing Coordinator (ABC)^TM. However, an individual patient's breath-hold (BH) reproducibility (RBH) may be improved in Deep Inspiration or Inspiration Breath-Hold (DIBH or IBH). This trial compared the tumor position RBH, stability (SBH), and breath-hold time (TBH) of three BH methods, using ABC, to personalize the selection of technique, by employing a pre-planning screening assessment.

METHODS: Patients planned for UA radiotherapy (kidney, pancreas, liver, or adrenal gland), were invited to participate in this prospective trial. Active Breathing Coordinator (ABC)^TM education was conducted, then participants attempted EBH, DIBH and IBH, in randomized order. During five consecutive BH's for each method, kV fluoroscopy images of the diaphragm were acquired. The BH technique selection was personalized according to a decision matrix. The EBH and the personalized technique cohort mean RBH and SBH of were analyzed.

RESULTS: Between May 2019 and March 2020, 19 participants were recruited. Median age of participants was 68 years (range 32-81). Tumor sites included kidney (n=1), adrenal gland (n=5) and liver (n=14). One participant was excluded due to poor BH compliance, leaving 270 images from 18 participants for analysis. Mean TBH was 22.1, 23.9 & 24.2 seconds for EBH, DIBH and IBH respectively. Screening selected EBH for 44% (n=8), IBH for 39% (n=7) and DIBH for 17% (n=3) of participants. The mean RBH was superior at 0.92mm (0.79mm SD) for the personalized technique, compared to EBH of 1.79mm (1.49mm SD) (p=0.016). Pre-planned subset analysis of participants whose personalized technique was not EBH showed improved mean RBH of 0.63mm (0.29mm SD) compared to their EBH RBH of 2.2mm (1.7mm SD) (p=0.011).

CONCLUSIONS: In 56% of participants, DIBH or IBH demonstrated superior RBH compared to EBH Personalized BH screening can inform selection of an ABC BH method which provides optimal RBH with improved TBH for an individual's planning and treatment course.

TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): XXX (withheld - blinded manuscript).

PMID:34384855 | DOI:10.1016/j.ijrobp.2021.08.001

Permalink for 'Prospective intra-individual blinded comparison of [(18)F]PSMA-1007 and [(68) Ga]Ga-PSMA-11 PET/CT imaging in patients with confirmed prostate cancer'

Prospective intra-individual blinded comparison of [(18)F]PSMA-1007 and [(68) Ga]Ga-PSMA-11 PET/CT imaging in patients with confirmed prostate cancer

Fetched: August 13th, 2021, 5:00am GMT by David A Pattison

Eur J Nucl Med Mol Imaging. 2021 Aug 12. doi: 10.1007/s00259-021-05520-y. Online ahead of print.

ABSTRACT

INTRODUCTION: [¹⁸F]PSMA-1007 has potential advantages over [⁶⁸ Ga]Ga-PSMA-11, although limited prospective data evaluating diagnostic performance exist. The aims of this study are to describe the concordance of [¹⁸FPSMA-1007 and [⁶⁸ Ga]Ga-PSMA-11 for TNM with the American Joint Committee on Cancer (AJCC) prognostic stage and assess differences in tracer uptake.

METHODS: Fifty men (mean age 71.8) were imaged with [⁶⁸ Ga]Ga-PSMA-11 and [¹⁸F]PSMA-1007 < 4 weeks apart. Images were independently reported according to TNM by two experienced nuclear medicine specialists blinded to the other scan and prior imaging. Discordant results were resolved by a third independent nuclear medicine specialist. Quantitative analysis of lesion uptake and physiologic tissue for each tracer was performed by one experienced reader.

RESULTS: Scan indications were initial staging (n = 12), biochemical recurrence (n = 27) and metastatic disease evaluation (n = 11). Most patients had ISUP grade group 3 or higher. Median PSA value was 2.7 ng/ml (IQR 0.7-12.0), and a minority of patients (28%) were currently treated with androgen deprivation therapy. [¹⁸F]PSMA-1007 uptake was significantly higher than [⁶⁸Ga]Ga-PSMA-11 in local recurrence, nodal and distant metastases and most physiologic sites (including bone) except for urinary bladder which was significantly lower. [¹⁸F]PSMA-1007 upstaged local prostate staging in 5/17 patients, local recurrence in 3/33 patients, regional nodal disease in 3/50 patients and 1 distant metastasis (bladder). [⁶⁸Ga]Ga-PSMA-11 upstaged regional nodal disease in 1/50 patients and distant metastasis in one patient (right adrenal). Overall AJCC prognostic stage was concordant in 46/50 (92%) patients, with two patients upstaged for both [¹⁸F]PSMA-1007 and [⁶⁸Ga]Ga-PSMA-11. [¹⁸F]PSMA-1007 had more equivocal results (one regional node; six equivocal bone lesions, one of which was subsequently confirmed metastatic) than [⁶⁸Ga]Ga-PSMA-11 (one equivocal local recurrence).

CONCLUSION: Overall AJCC prognostic stage was similar (92%) between [¹⁸F]PSMA-1007 and [⁶⁸Ga]Ga-PSMA-11. [¹⁸F]PSMA-1007 demonstrates higher uptake within involved nodes and distant metastases and most physiologic sites except urinary bladder which aided [¹⁸F]PSMA-1007 local staging of the prostate primary/local recurrence and regional nodal disease adjacent ureters. However, [¹⁸F]PSMA-1007 liver uptake obscured a solitary right adrenal metastasis, and more equivocal bone lesions were identified. Trial registration The study was registered with Australia New Zealand Clinical Trials Registry (ACTRN12618000665235) on 24 April 2018.

PMID:34383089 | DOI:10.1007/s00259-021-05520-y

SPECT-CT Imaging with [99mTc]PSMA-T4 in patients with Recurrent Prostate Cancer

Fetched: August 13th, 2021, 5:00am GMT by Sonya Sergieva

Nucl Med Rev Cent East Eur. 2021;24(2):70-81. doi: 10.5603/NMR.2021.0018.

ABSTRACT

BACKGROUND: Prostate-specific membrane antigen (PSMA) is a cell surface glycoprotein with a large extracellular domain with overexpression of the prostatic tumour cells. Several small molecules of PSMA ligands of inhibitors binding to the active site of PSMA were developed. [99mTc]Tc-PSMA-T4 is a new radiopharmaceutical (Polatom) for imaging loco-regional metastases and/or local relapse in patients with prostate cancer. The purpose of this work was to evaluate the clinical application of SPECT-CT imaging with [99mTc]Tc-PSMA-T4 in patients with recurrent prostate cancer.

MATERIAL AND METHODS: Thirty-six patients with prostate cancer, aged 60-80 years with biochemical relapse of PSA (ranged from 0.1 to 73 ng/mL) were included. Three patients were studied after tru-cut biopsy, hormonal and cytoreductive radiotherapy and 33 patients out of 36 - after radical treatment (total prostatectomy or definitive radiotherapy of the tumour). All of them underwent whole-body imaging examinations with subsequent target SPECT-CT studies of the pelvis, abdomen and/or chest, 1-3 hrs post i.v. administration of [99mTc]Tc-PSMA-T4. The average activity dose was 6.3 MBq/kg in a man of 70 kg. A Dual-head SPECT-CT gamma camera with a low dose CT scan (Symbia T2, Siemens) was used. The images were interpreted based on all other clinical and radiological data. Follow-up could be conducted in 11/36 patients during that period.

RESULTS: Normal biodistribution of the radiopharmaceutical with high activity background was observed in the liver, spleen, kidneys, lacrimal and salivary glands, bowels and urinary bladder. Positive imaging for local relapse in the prostate bad was imaged in 21 patients, lymph node metastases - in 16 cases, bone lesions - in 10 cases, pulmonary metastases - in 2 cases, hepatic lesions were visualised in one of them and in another - adrenal suprarenal metastasis with intensive tracer uptake significant for overexpression of PSMA. There was a suspicion for local recurrences in 4 patients with negative MRT studies who were followed up. In 3 cases, previously treated bone metastases were partially negative without tracer uptake, only some progressive bone lesions were positive. Five patients were with negative results. Sensitivity was 84.37% (27/32), specificity - 100% (4/4) and accuracy - 86.11% (31/36).

CONCLUSIONS: In conclusion SPECT-CT imaging with [99mTc]Tc-PSMA-T4 could be applied in patients with prostate cancer for the diagnosis of recurrent disease to determine personalized treatment for each patient. Specific uptake of this tracer, depicted by SPECT-CT images has clinical importance of identifying and assessing PSMA expression before consideration of Radio Ligand Therapy (RLT) with [¹⁷⁷Lu]Lu-PSMA. SPECT-CT imaging with [99mTc]PSMA is promising and reliable nuclear medicine approach to monitoring therapeutic effect after treatment and for restaging of the disease.

PMID:34382671 | DOI:10.5603/NMR.2021.0018

Erythema Nodosum Revealing Metastatic Lung Cancer

Fetched: August 12th, 2021, 5:00am GMT by Anis Mzabi

Eur J Case Rep Intern Med. 2021 Jul 21;8(7):002539. doi: 10.12890/2021_002539. eCollection 2021.

ABSTRACT

Erythema nodosum (EN) is an inflammatory condition of the subcutaneous fat and has been reported in patients with haematological malignancies (lymphomas) or solid tumours. Lung cancer is the most common cause of paraneoplastic syndrome. We report a case of EN occurring as a paraneoplastic disease. A 48-year-old Tunisian woman, a non-smoker with no relevant medical history, presented with painful, erythematous, firm nodules on her legs with ankle swelling. The patient did not report any other symptoms. There were no abnormalities on examination except for moderate fever. An extensive infectious and immunological investigation was negative. Antistreptolysin antibodies were undetectable. Chest radiography showed a focal opacity in the right lung and a CT scan revealed a mass in the lower right pulmonary lobe with hilar and mediastinal lymphadenopathies, a nodule in the right adrenal gland, condensation in the iliac bone and multiple bilateral nodular cerebral expansive processes. Bronchial biopsies revealed a primitive and moderately differentiated adenocarcinoma. No argument for tuberculosis or sarcoidosis was found.

LEARNING POINTS: Erythema nodosum (EN) can be idiopathic.EN has rarely been associated with lung cancer and so the association may be coincidental in our patient.The lung cancer was easily identified by chest x-ray in this case and in cases described in the literature.

PMID:34377687 | PMC:PMC8336736 | DOI:10.12890/2021_002539

The influence of TNF-α on the expression profile of key enzymes of steroidogenesis in H295R cells

Fetched: August 12th, 2021, 5:00am GMT by Beniamin Grabarek

Postepy Dermatol Alergol. 2021 Jun;38(3):404-411. doi: 10.5114/ada.2021.107926. Epub 2021 Jul 26.

ABSTRACT

INTRODUCTION: Tumor necrosis factor-α (TNF-α) plays an extremely important role in the regulation of hypothalamicpituitary-adrenal axis. It is believed that chronic inflammation is the main cause of cancerogenesis and TNF-α plays a significant role in both of these processes. Unfortunately, the function of TNF-α in human adrenal steroidogenesis has not been explained enough.

AIM: To evaluate the changes in transcriptional activity of STAR, CYP11A1, CYP11B1, and CYP11B2 in H295R cell line exposed to TNF-α.

MATERIAL AND METHODS: NCI-H295R, human adrenocortical cell line was exposed to human recombinant TNF-α at the concentrations ranging from 0.001 to 10 nM for 3, 12, 24, and 48 h. Cells not exposed to TNF-α were the control of this experiment. RTqPCR assay was used to determine the changes in the expression of genes encoding STAR, CYP11A1, CYP11B1, and CYP11B2.

RESULTS: The highest differences between stimulated and non-stimulated cells were observed in the expression of STAR (FC = +2.2; 0.01 nM of TNF-α; 48 h); CYP11A1 (FC = +3.5; 0.1 nM of TNF-α; 24 h); CYP11B1 (FC = +7.0; 10 nM of TNF-α; 48 h); CYP11B2 (FC = +2.5; 10 nM of TNF-α; 48 h). Statistically significant differences (p < 0.05) in the expression were found only for CYP11A1. The interaction effect between genes was also noticed (p < 0.05).

CONCLUSIONS: The research showed the impact of TNF-α on the expression of the key genes encoding enzymes involved in adrenal steroidogenesis. Different expression patterns of was observed, depending on time and TNF-α concentration increased synthesis of this pro-inflammatory cytokine may intensify adrenal steroidogenesis.

PMID:34377120 | PMC:PMC8330850 | DOI:10.5114/ada.2021.107926

Permalink for 'Primary Adrenal Insufficiency and Acute Cardiomyopathy in a Patient With Colorectal Cancer Treated With Dual Immune Checkpoint Inhibitors'

Primary Adrenal Insufficiency and Acute Cardiomyopathy in a Patient With Colorectal Cancer Treated With Dual Immune Checkpoint Inhibitors

Fetched: August 11th, 2021, 5:00am GMT by Arsenije Kojadinovic

Clin Colorectal Cancer. 2021 Jul 15:S1533-0028(21)00067-0. doi: 10.1016/j.clcc.2021.07.002. Online ahead of print.

NO ABSTRACT

PMID:34373203 | DOI:10.1016/j.clcc.2021.07.002

Syncope as the Initial Manifestation of a Late-Stage Renal Cell Carcinoma With Metastasis to the Brain

Fetched: August 10th, 2021, 5:00am GMT by Grace W Ying

Cureus. 2021 Jul 5;13(7):e16185. doi: 10.7759/cureus.16185. eCollection 2021 Jul.

ABSTRACT

Renal cell carcinoma (RCC) is the most common neoplasm that arises from renal parenchyma. About one-third of patients with RCC develop metastatic spread, with common sites including the lung, liver, bone, adrenal gland, and brain. Distant metastases can be difficult to detect unless symptoms appear. We report a case of a 56-year-old female who presented to the emergency department with the unresponsiveness of unknown duration. She underwent a thorough laboratory workup, and the computed tomography (CT) scan revealed a retroperitoneal mass originating from the right kidney and a large hemorrhagic brain mass in the left frontal lobe. The patient underwent emergent full craniotomy for tumor removal, and histology confirmed metastatic RCC. Since several patients with RCC are asymptomatic, the slow growth of tumors leading to distant metastasis can be overlooked. Thus, this case demonstrates the importance of early detection of RCC to help prevent or delay further disease progression.

PMID:34367792 | PMC:PMC8335967 | DOI:10.7759/cureus.16185

Anaesthetic challenges in perioperative management of thoracic paraganglioma in an 8-year-old child

Fetched: August 10th, 2021, 5:00am GMT by Ram Gopal Maurya

BMJ Case Rep. 2021 Aug 5;14(8):e243521. doi: 10.1136/bcr-2021-243521.

ABSTRACT

Pheochromocytomas (PCC) are catecholamine-secreting tumours that arise from chromaffin cells of the sympathoadrenal system. These rare catecholamine-secreting tumours arising from adrenal glands are termed as PCC and those from extra--adrenal sites are termed paraganglioma (PGL). Thoracic PGL is very rarely found. we report the anaesthetic challenges and management of an 8-year-old child with functional thoracic PGL and its successful outcome.

PMID:34353832 | PMC:PMC8344272 | DOI:10.1136/bcr-2021-243521

Gestational Diabetes

Fetched: August 10th, 2021, 5:00am GMT by Erin M. Cleary

2021 Jul 26. 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

Gestational diabetes (GDM) is characterized by glucose intolerance first manifesting during pregnancy and is an important driver for fetal macrosomia, birth injury, and neonatal metabolic alterations--particularly when persistent maternal hyperglycemia exists. Individuals with GDM face short term complications such as cesarean section and hypertensive disorders, and significantly increased risk for type 2 diabetes over the subsequent 10-20 years. Many of these concerns may be moderated with lifestyle and pharmacotherapeutic interventions to reduce maternal hyperglycemia and thereby improve maternal and neonatal health. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:34370430 | Bookshelf:NBK572755

Pregestational Diabetes Mellitus

Fetched: August 10th, 2021, 5:00am GMT by Erin M. Cleary

ABSTRACT

The physiologic changes which occur during the reproductive cycle are vast and involve every body system. In this chapter, we will review the metabolic changes that occur during normal pregnancies and those affected by pre-gestational diabetes. Due to the significant overlap in maternal and perinatal risks secondary to pre-gestational diabetes and obesity, we will review the risks of maternal obesity and hyperglycemia on maternal, fetal, and neonatal outcomes. Management of preexisting diabetes in pregnancy will be reviewed in detail including up to date medications and diabetes technologies. Postpartum issues including changes in insulin sensitivity, breastfeeding and contraception for women with preexisting diabetes will be discussed. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:34370429 | Bookshelf:NBK572754

Anaerobic Infections and Endocrinology

Fetched: August 10th, 2021, 5:00am GMT by Amrutha Lakhotia

2021 Jul 14. 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

Anaerobic bacteria are present as part of the normal microbial flora in the human body. These bacteria turn virulent whenever the host defense mechanisms are compromised. Diabetes and glucocorticoid abuse are the two common endocrine conditions that predisposes individuals to anaerobic infections. Anaerobic infections are common in tropical countries and can affect any tissue or gland resulting in severe organ dysfunction. Microbial endocrinology deals with the bidirectional interaction between the hormones and the microbes. The interaction is influenced by the virulence factors released from the microbes, inflammatory mediators, and the hormonal dysfunction. In this chapter, we shall discuss the various anaerobic bacterial infections relevant in endocrinology practices. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:34370428 | Bookshelf:NBK572753

Immune-Related Endocrine Dysfunctions in Combined Modalities of Treatment: Real-World Data

Fetched: August 8th, 2021, 5:00am GMT by Wing-Lok Chan

Cancers (Basel). 2021 Jul 28;13(15):3797. doi: 10.3390/cancers13153797.

ABSTRACT

The number of immune-related endocrine dysfunctions (irEDs) has concurrently increased with the widespread use of immunotherapy in clinical practice and further expansion of the approved indications for immune checkpoint inhibitor (ICI) in cancer management. A retrospective analysis was conducted on consecutive patients ≥18 years of age with advanced solid malignancies who had received at least one dose of anti-programmed cell death protein 1 (anti-PD-1) and/or anti-CTLA4 antibodies between January 2014 and December 2019 at a university hospital in Hong Kong. Patients were reviewed up to two months after the last administration of an ICI. The types, onset times and grades of irEDs, including hypothyroidism, hyperthyroidism, adrenal insufficiency and immune-related diabetes mellitus, were recorded. Factors associated with irEDs were identified using multivariate analysis. A total of 953 patients (male: 603, 64.0%; median age: 62.0 years) were included. Of these, 580 patients (60.9%) used ICI-alone, 132 (13.9%) used dual-ICI, 187 (19.6%) used an ICI combined with chemotherapy (chemo + ICI), and 54 (5.70%) used immunotherapy with a targeted agent (targeted + ICI). A significantly higher proportion of patients using targeted + ICI had irEDs and hypothyroidism; in contrast, a higher proportion of patients using dual-ICI had adrenal insufficiency. There was no significant difference in the incidence of irED between the younger (<65 years) and older (≥65 years) patients. Using logistic regression, only treatment type was significantly associated with irEDs. Notably, older patients had a higher risk of having immune-related diabetes mellitus. This large, real-world cohort demonstrates that targeted + ICI has a higher risk of overall irED and hypothyroidism. Immunotherapy is safe and well-tolerated regardless of age, but close monitoring of fasting glucose is essential in older populations.

PMID:34359698 | PMC:PMC8345182 | DOI:10.3390/cancers13153797

Re-Challenging with Nivolumab in Metastatic Renal Cell Carcinoma After Immune-Related Interstitial Pneumonia: A Case Report

Fetched: August 7th, 2021, 5:00am GMT by Yosuke Shibata

Am J Case Rep. 2021 Aug 6;22:e932924. doi: 10.12659/AJCR.932924.

ABSTRACT

BACKGROUND The efficacy and safety of re-challenge with immune checkpoint inhibitors after immune-related adverse events have not been established. We report a case of successful re-administration of nivolumab in metastatic renal cell carcinoma after discontinuation due to immune-related adverse events. CASE REPORT Laparoscopic nephrectomy was performed on a 52-year-old man diagnosed with renal cell carcinoma pT1bN0M0. After surgery, left adrenal and lung metastases appeared. Nivolumab was administered as a sixth-line therapy, and he achieved a partial response, but interstitial pneumonia occurred. He was diagnosed with grade 2 immune-related adverse events, and nivolumab treatment was discontinued. Interstitial pneumonia was well controlled by steroids. He maintained a partial response for a long time, and the lung metastases disappeared 7 months after discontinuation. However, bilateral lung metastases reappeared 10 months after the discontinuation. We decided to re-administer nivolumab, while carefully monitoring the patient and fully explaining the risk of recurrence of immune-related adverse events. After 5 cycles of re-administration, computed tomography revealed a reduction in metastases without re-activation of interstitial pneumonia. He experienced a grade 1 fever the day after re-administration, but continued nivolumab therapy without other adverse events. After 7 cycles of re-administration, the lung metastases increased, and nivolumab treatment was terminated. Two months later, a grade 2 interstitial pneumonia recurred, but improved rapidly with oral steroids. CONCLUSIONS For patients who have discontinued immune checkpoint inhibitors due to immune-related adverse events, re-challenge of immune checkpoint inhibitors may be an option after explaining the risk of relapse of immune-related adverse events.

PMID:34358221 | PMC:PMC8351298 | DOI:10.12659/AJCR.932924

Permalink for 'Synthesis and pharmacological evaluation of [18F]PBR316: a novel PET ligand targeting the translocator protein 18 kDa (TSPO) with low binding sensitivity to human single nucleotide polymorphism rs6971'

Synthesis and pharmacological evaluation of [18F]PBR316: a novel PET ligand targeting the translocator protein 18 kDa (TSPO) with low binding sensitivity to human single nucleotide polymorphism rs6971

Fetched: August 7th, 2021, 5:00am GMT by Filomena Mattner

RSC Med Chem. 2021 Apr 19;12(7):1207-1221. doi: 10.1039/d1md00035g. eCollection 2021 Jul 21.

ABSTRACT

Radiopharmaceuticals that target the translocator protein 18 kDa (TSPO) have been investigated with positron emission tomography (PET) to study neuroinflammation, neurodegeneration and cancer. We have developed the novel, achiral, 2-phenylimidazo[1,2-a]pyridine, PBR316 that targets the translocator protein 18 kDa (TSPO) that addresses some of the limitations inherent in current TSPO ligands; namely specificity in binding, blood brain barrier permeability, metabolism and insensitivity to TSPO binding in subjects as a result of rs6971 polymorphism. PBR316 has high nanomolar affinity (4.7-6.0 nM) for the TSPO, >5000 nM for the central benzodiazepine receptor (CBR) and low sensitivity to rs6971 polymorphism with a low affinity binders (LABs) to high affinity binders (HABs) ratio of 1.5. [¹⁸F]PBR316 was prepared in 20 ± 5% radiochemical yield, >99% radiochemical purity and a molar activity of 160-400 GBq μmol^-1. Biodistribution in rats showed high uptake of [¹⁸F]PBR316 in organs known to express TSPO such as heart (3.9%) and adrenal glands (7.5% ID per g) at 1 h. [¹⁸F]PBR316 entered the brain and accumulated in TSPO-expressing regions with an olfactory bulb to brain ratio of 3 at 15 min and 7 at 4 h. Radioactivity was blocked by PK11195 and Ro 5-4864 but not Flumazenil. Metabolite analysis showed that radioactivity in adrenal glands and the brain was predominantly due to the intact radiotracer. PET-CT studies in mouse-bearing prostate tumour xenografts indicated biodistribution similar to rats with radioactivity in the tumour increasing with time. [¹⁸F]PBR316 shows in vitro binding that is insensitive to human polymorphism and has specific and selective in vivo binding to the TSPO. [¹⁸F]PBR316 is suitable for further biological and clinical studies.

PMID:34355185 | PMC:PMC8292990 | DOI:10.1039/d1md00035g

Permalink for 'Identification of novel lipid metabolic biomarkers associated with poor adrenocortical carcinoma prognosis using integrated bioinformatics'

Identification of novel lipid metabolic biomarkers associated with poor adrenocortical carcinoma prognosis using integrated bioinformatics

Fetched: August 7th, 2021, 5:00am GMT by Chitra Subramanian

Surgery. 2021 Aug 2:S0039-6060(21)00554-7. doi: 10.1016/j.surg.2021.04.049. Online ahead of print.

ABSTRACT

BACKGROUND: Adrenocortical carcinoma while rare, often presents with advanced metastatic disease carrying a 5-year survival of <15%. Despite adrenocortical carcinoma tumors having high avidity for cholesterol, the role of lipids in adrenocortical carcinoma has not been well described. Therefore, we performed an integrated bioinformatic analysis to identify novel lipid biomarkers correlating with poor survival that may help identify adrenocortical carcinoma tumor progression or therapy resistance.

METHODS: A meta-analysis of collated adrenocortical carcinoma studies from the correlation engine identified lipid metabolism genes differentially expressed between adrenocortical carcinoma and the normal adrenal, which were then selected for enrichment analysis by the Database for Annotation, Visualization and Integrated Discovery database. A protein-protein interaction network of genes was constructed using Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape. Top hub genes identified were validated using the Xena database. Survival analysis of hub genes was performed in the R2 genomic analysis platform using The Cancer Genome Atlas program data set.

RESULTS: Examination of pathways by correlation engine identified a unique subset of lipid metabolism-related genes that are differentially regulated in adrenocortical carcinoma tumors versus normal tissues (P < .01). Enrichment pathway analysis in Database for Annotation, Visualization and Integrated Discovery indicated that genes involved in sphingolipid, steroid, and peroxisome proliferator-activated receptor-α metabolism is upregulated in adrenocortical carcinoma, whereas glycerol phospholipid, fatty acid, and phosphatidylinositol metabolism are downregulated. Survival analysis of differentially regulated genes indicated that upregulation of SGPL1, FDFT1, SQLE and downregulation of PIK3C2B, PIK3CD, SYNJ2, DGAT1, PLA2G16, PLD1, GPD1 are all significantly associated with poor overall survival (P < .05) in adrenocortical carcinoma patients.

CONCLUSION: Upregulation of sphingolipid and steroid synthesis genes and downregulation of phosphatidylinositol and glycerol phospholipid metabolism are associated with worse survival in patients with adrenocortical carcinoma.

PMID:34353633 | DOI:10.1016/j.surg.2021.04.049

Melanoma Metastases to the Adrenal Gland Are Highly Resistant to Immune Checkpoint Inhibitors

Fetched: August 5th, 2021, 5:00am GMT by Jessica S W Borgers

J Natl Compr Canc Netw. 2021 Aug 4:jnccn20283. doi: 10.6004/jnccn.2020.7800. Online ahead of print.

ABSTRACT

BACKGROUND: Adrenal gland metastases (AGMs) are common in advanced-stage melanoma, occurring in up to 50% of patients. The introduction of immune checkpoint inhibitors (ICIs) has markedly altered the outcome of patients with melanoma. However, despite significant successes, anecdotal evidence has suggested that treatment responses in AGMs are significantly lower than in other metastatic sites. We sought to investigate whether having an AGM is associated with altered outcomes and whether ICI responses are dampened in the adrenal glands.

PATIENTS AND METHODS: We retrospectively compared ICI responses and overall survival (OS) in 68 patients with melanoma who were diagnosed with an AGM and a control group of 100 patients without AGMs at a single institution. Response was determined using RECIST 1.1. OS was calculated from time of ICI initiation, anti-PD-1 initiation, initial melanoma diagnosis, and stage IV disease diagnosis. Tumor-infiltrating immune cells were characterized in 9 resected AGMs using immunohistochemical analysis.

RESULTS: Response rates of AGMs were significantly lower compared with other metastatic sites in patients with AGMs (16% vs 22%) and compared with those without AGMs (55%). Patients with AGMs also had significantly lower median OS compared with those without AGMs (3.1 years vs not reached, respectively). We further observed that despite this, AGMs exhibited high levels of tumor-infiltrating immune cells.

CONCLUSIONS: In this cohort of patients with melanoma, those diagnosed with an AGM had lower ICI response rates and OS. These results suggest that tissue-specific microenvironments of AGMs present unique challenges that may require novel, adrenal gland-directed therapies or surgical resection.

PMID:34348236 | DOI:10.6004/jnccn.2020.7800

Permalink for 'Impact of Daily Plan Adaptation on Organ-At-Risk Normal Tissue Complication Probability for Adrenal Lesions undergoing Stereotactic Ablative Radiation Therapy'

Impact of Daily Plan Adaptation on Organ-At-Risk Normal Tissue Complication Probability for Adrenal Lesions undergoing Stereotactic Ablative Radiation Therapy

Fetched: August 4th, 2021, 5:00am GMT by Hanbo Chen

Radiother Oncol. 2021 Jul 31;163:14-20. doi: 10.1016/j.radonc.2021.07.026. Online ahead of print.

ABSTRACT

INTRODUCTION: Stereotactic ablative radiotherapy (SABR) can achieve good local control for metastatic adrenal lesions. Magnetic resonance (MR)-guidance with daily on-table plan adaptation can augment the delivery of SABR with greater dose certainty. The goal of this study was to quantify the potential clinical benefit MR-guided daily-adaptive adrenal SABR using the normal tissue complication probability (NTCP) framework.

METHODS: Patients treated with adrenal MR-guided SABR at a single institution were retrospectively reviewed. Lyman-Kutcher-Burman NTCP models were used to calculate the NTCP of upper abdominal organs-at-risk (OARs) at simulation and both before and after daily on-table plan adaptation. Differences in OAR NTCPs were assessed using signed-rank tests. Potential predictors of the benefits of adaptation were assessed by linear regression.

RESULTS: Fifty-two adrenal MR-guided SABR courses were analyzed. The baseline simulation plan underestimated the absolute stomach NTCP by 10.0% on average (95% confidence interval: 4.7-15.2%, p < 0.001). Daily on-table adaptation lowered absolute NTCP by 8.7% (4.2-13.2%, p < 0.001). The most significant predictor of the benefits of adaptation was lesion laterality (p = 0.018), with left-sided lesions benefitting more (13.3% [6.3-20.4%], p < 0.001) than right-sided lesions (2.1% [-1.6-5.7%], p = 0.25). Sensitivity analyses did not change the statistical significance of the findings.

CONCLUSION: NTCP analysis revealed that patients with left adrenal tumors were more likely to benefit from MR-guided daily on-table adaptive SABR using current dose/fractionation regimens due to reductions in predicted gastric toxicity. Right-sided adrenal lesions may be considered for dose escalation due to low predicted NTCP.

PMID:34343546 | DOI:10.1016/j.radonc.2021.07.026

Permalink for 'Neurofibromatosis Type 1 with Concurrent Multiple Endocrine Disorders: Adenomatous Goiter, Primary Hyperparathyroidism, and Acromegaly'

Neurofibromatosis Type 1 with Concurrent Multiple Endocrine Disorders: Adenomatous Goiter, Primary Hyperparathyroidism, and Acromegaly

Fetched: August 4th, 2021, 5:00am GMT by Shigemitsu Yasuda

Intern Med. 2021;60(15):2451-2459. doi: 10.2169/internalmedicine.4981-20. Epub 2021 Aug 1.

ABSTRACT

We encountered a 70-year-old Japanese woman with neurofibromatosis type 1 (NF1) who had a history of pheochromocytoma and concurrently developed adenomatous goiter, primary hyperparathyroidism, and acromegaly. The patient had a somatotroph adenoma of the adenohypophysis that predisposed her to multinodular goiter. Three parathyroid tumors were detected by cervical ultrasonography and cervicothoracic computed tomography. Genetic analyses did not reveal genetic alterations (e.g. loss-of-function mutation) in the causative genes of endocrine tumors, including MEN1, RET, VHL, CDKN1B, and CDKN2C. The NF1 gene could not be analyzed genetically due to the patient's refusal. The pathophysiologic mechanisms of endocrinopathy concurrence in NF1 remain to be elucidated.

PMID:34334593 | DOI:10.2169/internalmedicine.4981-20

Neuroendocrine and Adrenal Tumors, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

Fetched: August 3rd, 2021, 5:00am GMT by Manisha H Shah

J Natl Compr Canc Netw. 2021 Jul 28;19(7):839-868. doi: 10.6004/jnccn.2021.0032.

ABSTRACT

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Neuroendocrine and Adrenal Gland Tumors focus on the diagnosis, treatment, and management of patients with neuroendocrine tumors (NETs), adrenal tumors, pheochromocytomas, paragangliomas, and multiple endocrine neoplasia. NETs are generally subclassified by site of origin, stage, and histologic characteristics. Appropriate diagnosis and treatment of NETs often involves collaboration between specialists in multiple disciplines, using specific biochemical, radiologic, and surgical methods. Specialists include pathologists, endocrinologists, radiologists (including nuclear medicine specialists), and medical, radiation, and surgical oncologists. These guidelines discuss the diagnosis and management of both sporadic and hereditary neuroendocrine and adrenal tumors and are intended to assist with clinical decision-making. This article is focused on the 2021 NCCN Guidelines principles of genetic risk assessment and counseling and recommendations for well-differentiated grade 3 NETs, poorly differentiated neuroendocrine carcinomas, adrenal tumors, pheochromocytomas, and paragangliomas.

PMID:34340212 | DOI:10.6004/jnccn.2021.0032

Second Primary Cancers After Kidney Cancers, and Kidney Cancers as Second Primary Cancers

Fetched: August 3rd, 2021, 5:00am GMT by Guoqiao Zheng

Eur Urol Open Sci. 2021 Jan 9;24:52-59. doi: 10.1016/j.euros.2020.12.007. eCollection 2021 Feb.

ABSTRACT

BACKGROUND: Second primary cancers (SPCs) are increasing due to improving survival in first primary cancers. Previous studies on SPCs in renal cell carcinoma (RCC) have focused on treatment and other risk factors, but data of RCC as an SPC are scarce.

OBJECTIVE: In this study, we want to elucidate the risk for any SPC after RCC, and in reverse order, for RCC as an SPC after any cancer. We additionally consider how family histories influence the risks.

DESIGN SETTING AND PARTICIPANTS: Patient data were obtained from the Swedish Cancer Registry from years 1990 through 2015, and family data were obtained from the Multigeneration Register.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We employed standardized incidence ratios to estimate bidirectional relative risks of subsequent cancer associated with RCC.

RESULTS AND LIMITATIONS: We identified 17 587 RCCs (60% in male patients). The highest increases for SPCs were observed for nervous system hemangioblastoma (HB; 26.8), adrenal (12.09) tumors, and renal pelvic cancer (6.32). In the reverse order, RCC as an SPC, nervous system HB (17.01), and adrenal tumors (15.34) were associated with the highest risks. Risks for many other sites (12 sites and subsites) were increased bidirectionally. For women, a total of seven sites and subsites were increased bidirectionally, and many were shared with men. The only significant sex difference in SPCs was the higher lung cancer risk in women (2.41) than in men (1.28). Patients with a family history of HBs or of prostate, colorectal and lung cancers showed high risks of these cancers as SPCs after RCC. Family history accounted for 30% of prostate cancers after RCC.

CONCLUSIONS: The bidirectional study design was able to suggest risk factors for SPCs and offered a clinical take-home message urging to consider strategies for early detection and prevention of SPCs. Readily available information on lifestyle (eg, smoking) and family history (eg, prostate cancer) may reveal targets for risk reduction with prognostic benefits.

PATIENT SUMMARY: Close to 10% of kidney cancer patients develop another cancer. The cause for these other cancers may not depend on kidney cancer.

PMID:34337496 | PMC:PMC8317822 | DOI:10.1016/j.euros.2020.12.007

Pancreatobiliary Adenocarcinoma in a Gastric Duplication Cyst: A Doubly Rare Diagnosis

Fetched: August 3rd, 2021, 5:00am GMT by Ana Rolo

Cureus. 2021 Jun 29;13(6):e16025. doi: 10.7759/cureus.16025. eCollection 2021 Jun.

ABSTRACT

Gastric duplication cyst (GDC) is a rare congenital abnormality and the development of malignant transformation in these lesions is even rarer, with only few reported cases worldwide to date. We hereby report an additional case of cancer arising from a GDC in a 54-year-old male. The patient's chief complaints were abdominal pain and significant weight loss. Computed tomography and endoscopy ultrasonography (EUS) revealed a nodular formation with a cystic component, localized in the great gastric curvature and invading the spleen and left adrenal gland. The biopsy from EUS was inconclusive. After exploratory laparotomy, the patient was submitted to an en-bloc resection with partial gastrectomy, splenectomy and left adrenalectomy. Histopathologic examination revealed a cystic mass non-communicating with the gastric wall. Immunohistochemistry staining showed a moderately differentiated pancreatobiliary adenocarcinoma within a duplication cyst with lymphovascular and perineural invasion. The patient was proposed to adjuvant systemic treatment, however, after few months he developed metachronous metastasis. To our knowledge, this is the first case of adenocarcinoma with pancreatobiliary differentiation arising from a gastric duplication cyst.

PMID:34336513 | PMC:PMC8319232 | DOI:10.7759/cureus.16025

Warning against second-generation antiandrogen for metastatic castration sensitive prostate cancer

Fetched: August 2nd, 2021, 5:00am GMT by Takahiro Inoue

BJU Int. 2021 Aug 1. doi: 10.1111/bju.15561. Online ahead of print.

ABSTRACT

Growing evidence showed that the use of next-generation androgen receptor axis-targeted agents (ARATs) and/or docetaxel improves both progression-free and overall survival in metastatic hormone-sensitive prostate cancer (mCSPC) (1). ARATs include abiraterone acetate, enzalutamide, and apalutamide. Abiraterone acetate blocks CYP17A1, which reduces testosterone synthesis from adrenal androgens or cholesterol in the testis, adrenal glands, and prostate cancer cells (2).

PMID:34333840 | DOI:10.1111/bju.15561

Multiple corticosteroid abnormalities in cats with hyperaldosteronism

Fetched: August 1st, 2021, 5:00am GMT by Daniel K Langlois

J Vet Intern Med. 2021 Jul 31. doi: 10.1111/jvim.16224. Online ahead of print.

ABSTRACT

BACKGROUND: The frequency with which multiple corticosteroid abnormalities occur in cats with aldosterone secreting adrenocortical tumors is unknown.

OBJECTIVES: To evaluate adrenal-derived corticosteroids in cats in which blood samples were submitted for measure of aldosterone.

ANIMALS: Two hundred ninety-seven cats.

METHODS: Retrospective study. Analysis of a convenience sample of previously submitted serum or plasma. Progesterone, corticosterone, and cortisol were measured in feline serum or plasma samples submitted to an endocrinology laboratory for aldosterone measurements. Demographics and clinical history were retrieved from submittal forms when provided. Statistical testing was performed to investigate associations among the adrenal corticosteroids.

RESULTS: Progesterone and corticosterone concentrations were strongly correlated (ρ = 0.74; P < .001). Progesterone (median, 5 nmol/L; interquartile range, 3-10 nmol/L) and corticosterone (113 nmol/L, 38-250 nmol/L) in cats with markedly increased aldosterone concentrations (≥3000 pmol/L) were higher than progesterone (1 nmol/L, 1-2 nmol/L) and corticosterone (12 nmol/L, 3-25 nmol/L) in cats with normal aldosterone concentrations (P < .001 for both comparisons). Progesterone concentrations ≥10 nmol/L (normal, ≤2 nmol//L) occurred in 24 of 76 (32%) cats with aldosterone concentrations ≥3000 pmol/L. Cortisol was lower in cats with aldosterone concentrations ≥3000 pmol/L as compared to those with aldosterone concentrations <500 pmol/L (59 nmol/L, 27-103 nmol/L vs 103 nmol/L, 49-182 nmol/L; P = .002).

CONCLUSIONS AND CLINICAL IMPORTANCE: Multiple corticosteroid abnormalities occur in a subset of cats with hyperaldosteronism. The magnitude of increases in progesterone and corticosterone in some cats with hyperaldosteronism is likely to be clinically relevant.

PMID:34331479 | DOI:10.1111/jvim.16224

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

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

Condition: Adrenocortical Carcinoma
Intervention: Drug: Pembrolizumab / Lenvatinib
Sponsor: National Cancer Center, Korea
Not yet 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

Nivolumab and Ipilimumab in Treating Patients With Rare Tumors

Posted: July 15th, 2016, 2:00pm GMT

An Adrenocortical Carcinoma Evolving After Nine Years of Latency From a Small Adrenal Incidentaloma

Fetched: September 16th, 2021, 5:00am GMT by Harpreet S Kohli

Cureus. 2021 Aug 3;13(8):e16851. doi: 10.7759/cureus.16851. eCollection 2021 Aug.

ABSTRACT

PMID:34522492 | PMC:PMC8425154 | DOI:10.7759/cureus.16851

Oncocytic Adrenocortical Carcinoma With Low (18)F-FDG Uptake and the Absence of Glucose Transporter 1 Expression

Fetched: September 14th, 2021, 5:00am GMT by Naru Babaya

J Endocr Soc. 2021 Aug 23;5(11):bvab143. doi: 10.1210/jendso/bvab143. eCollection 2021 Nov 1.

ABSTRACT

Adrenocortical carcinoma (ACC) is a rare tumor, and some histological variants (oncocytic, myxoid, and sarcomatoid ACCs) have been reported in addition to the conventional ACC. Among these subtypes, oncocytic ACC is histologically characterized by the presence of abundant eosinophilic granular cytoplasm in the carcinoma cells owing to the accumulation of mitochondria, which generally yields high ¹⁸F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET). Herein, we report the case of a 21-year-old woman with oncocytic ACC with low FDG uptake on PET scan. Her circulating levels of androgens were high, and androgen-synthesis enzymes were detected in carcinoma cells. The patient also had hypocholesterolemia. However, glucose transporter 1 (GLUT1) was not detected in the tumor, which was considered to account for the low FDG uptake by the tumor. To the best of our knowledge, this is the first case of low FDG uptake by oncocytic ACC without GLUT1 expression. Additionally, since hypocholesterolemia was reported in 3 previous reports of androgen-producing tumors, a possible correlation between androgenicity in adrenal tumors and the development of hypocholesterolemia could be postulated; however, further investigations are needed for clarification. This case highlights important information regarding the diversity of ACC and its impact on hypocholesterolemia.

PMID:34514280 | PMC:PMC8423427 | DOI:10.1210/jendso/bvab143

Permalink for 'Role of Bclaf1 in Promoting Adrenocortical Carcinoma Proliferation: A Study Combining the Use of Bioinformatics and Molecular Events'

Role of Bclaf1 in Promoting Adrenocortical Carcinoma Proliferation: A Study Combining the Use of Bioinformatics and Molecular Events

Fetched: September 14th, 2021, 5:00am GMT by Hui Zhou

Cancer Manag Res. 2021 Aug 31;13:6785-6795. doi: 10.2147/CMAR.S316599. eCollection 2021.

ABSTRACT

PURPOSE: Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis, and researchers are interested in further studying its diagnosis and treatment. Our study aims to identify new potential therapeutic targets in ACC.

PATIENTS AND METHODS: The core genes CDK1 and CCNB1 were previously screened using ACC data from The Cancer Genome Atlas (TCGA) as the most relevant to Bclaf1 and tumour prognosis. We used siRNA- or shRNA-based models to explore the role of Bcl-2-associated transcription factor 1 (Bclaf1) in SW-13 cell lines. Western blotting and qPCR were used to determine the effects of Bclaf1 on CDK1 and Cyclin B1.

RESULTS: Based on biological information analysis, we found that Bcl-2-associated transcription factor 1 (Bclaf1) affected the progression of ACC and was associated with the cell cycle. Downregulated Bclaf1 expression inhibited the proliferation of SW-13 cells and affected the cell cycle process of SW-13 cells. BCLAF1 was correlated with CDK1 and CCNB1 and can regulate their mRNA and protein levels.

CONCLUSION: Bclaf1 might promote the development of ACC by regulating CDK1 and Cyclin B1 to drive mitosis.

PMID:34512018 | PMC:PMC8418367 | DOI:10.2147/CMAR.S316599

Permalink for 'Beckwith-Wiedemann syndrome: Clinical, histopathological and molecular study of two Tunisian patients and review of literature'

Beckwith-Wiedemann syndrome: Clinical, histopathological and molecular study of two Tunisian patients and review of literature

Fetched: September 13th, 2021, 5:00am GMT by Hela Sassi

Mol Genet Genomic Med. 2021 Sep 12:e1796. doi: 10.1002/mgg3.1796. Online ahead of print.

ABSTRACT

BACKGROUND: Beckwith-Wiedemann syndrome (BWS) is a rare overgrowth syndrome characterized by congenital malformations and predisposition to embryonic tumors. Loss of methylation of imprinting center 2 (IC2) is the most frequent alteration and rarely associated with tumors compared to paternal uniparental disomy of chromosome 11 (UPD(11)pat) and gain of methylation of imprinting center 1.

METHODS: Our study aimed to describe the clinical, histopathological and genetic characteristics of two patients and establish genotype-phenotype correlations. The clinical diagnosis was based on the criteria defined by the international expert consensus of BWS. Molecular study of 11p15.5 methylation status was assessed using methylation-specific-multiplex ligation probe amplification (MS-MLPA).

RESULTS: Patients were aged 12 months and 3 months and fulfilled the clinical score of BWS. MS-MLPA showed molecular alterations consisting of loss of methylation in IC2 (IC2-LOM) at the maternal allele for one patient and a mosaic UPD(11)pat for the second patient in whom follow-up at 6months revealed adrenocortical carcinoma (ACC) with low grade of malignancy. Molecular subtypes guide the follow-up and tumor surveillance, our major concern.

CONCLUSION: We have to take into account the psychological impact of a possible tumor whatever the underlying mechanism is. Nevertheless, the tumor risk remains high for UPD(11)pat. Our study extended the phenotype of BWS with absence of macrosomia in Tunisian patients, contrasting with literature, and added a supplementary case of ACC in the tumor spectrum of BWS patients with UPD(11)pat.

PMID:34510813 | DOI:10.1002/mgg3.1796

How to Differentiate Benign from Malignant Adrenocortical Tumors?

Fetched: September 12th, 2021, 5:00am GMT by Charlotte L Viëtor

Cancers (Basel). 2021 Aug 30;13(17):4383. doi: 10.3390/cancers13174383.

ABSTRACT

PMID:34503194 | PMC:PMC8431066 | DOI:10.3390/cancers13174383

Permalink for 'A case of estrogen-secreting adrenocortical carcinoma: Comprehensive immunohistochemical analysis of disorganized steroid genesis'

A case of estrogen-secreting adrenocortical carcinoma: Comprehensive immunohistochemical analysis of disorganized steroid genesis

Fetched: September 10th, 2021, 5:00am GMT by Megumi Yokoyama

IJU Case Rep. 2021 Jun 28;4(5):318-321. doi: 10.1002/iju5.12336. eCollection 2021 Sep.

ABSTRACT

INTRODUCTION: Adrenocortical carcinoma rarely secretes estrogens, and little is known regarding the mechanism of intra-tumor estrogen production. We report an estrogen-secreting adrenocortical carcinoma in a postmenopausal woman, where comprehensive immunohistochemical analyses of the resected tumor revealed disorganized steroidogenesis.

CASE PRESENTATION: A 68-year-old woman presented with postmenopausal vaginal bleeding and was found to have a left adrenal tumor. Serum estradiol and testosterone were elevated but they normalized after resection of the tumor, suggestive of adrenocortical carcinoma with disorganized steroidogenesis. Immunohistochemical analyses revealed that the tumor expressed aromatase which converts androgens into estrogens. Furthermore, the tumor lacked 17βHSD2, which converts estradiol to estrone, suggesting that estradiol accumulated as the final product of the tumor's steroidogenic pathway.

CONCLUSION: The capability of adrenocortical carcinoma to produce estrogen can be demonstrated by comprehensive immunohistochemical analyses of steroidogenic enzymes, such as those reported here.

PMID:34497994 | PMC:PMC8413203 | DOI:10.1002/iju5.12336

Evaluation of Necrosis as a Diagnostic and Prognostic Indicator in Adrenocortical Carcinoma

Fetched: September 9th, 2021, 5:00am GMT by Sarah S Pearlstein

JAMA Surg. 2021 Sep 8. doi: 10.1001/jamasurg.2021.3646. Online ahead of print.

NO ABSTRACT

PMID:34495300 | DOI:10.1001/jamasurg.2021.3646

Pan-Cancer Analysis Identified C1ORF112 as a Potential Biomarker for Multiple Tumor Types

Fetched: September 8th, 2021, 5:00am GMT by Jiaxuan Chen

Front Mol Biosci. 2021 Aug 19;8:693651. doi: 10.3389/fmolb.2021.693651. eCollection 2021.

ABSTRACT

C1ORF112 is an evolutionarily conserved gene across vertebrates. Over the last decade, studies have suggested that C1ORF112 may play a role in tumorigenesis. Using The Cancer Genome Atlas datasets, we explored the role of C1ORF112 across various tumor types in this study. In most tumor types, C1ORF112 expression was increased in tumor tissues compared to corresponding non-tumor tissues. In patients with certain tumor types, higher C1ORF112 expression was correlated with shorter overall survival, disease-free survival, and progression-free survival. Further analyses of C1ORF112 genetic alteration data showed that C1ORF112 amplification and mutations may have an impact on liver hepatocellular carcinoma and uterine corpus endometrial carcinoma prognosis. In cancers including lower grade glioma and adrenocortical carcinoma, C1ORF112 expression was linked to cancer-associated fibroblast infiltration. Gene Ontology analysis showed that C1ORF112 was co-expressed with genes involved in biological processes such as cell cycle and mitotic regulation. The protein interaction network demonstrated that C1ORF112 physically interacted with RAD51, DMC1, and FIGNL1, which have well characterized functions in DNA repair and cell cycle regulation. This pan-cancer study revealed the prognostic value and oncogenic role of C1ORF112 across multiple tumor types.

PMID:34490347 | PMC:PMC8416665 | DOI:10.3389/fmolb.2021.693651

Management of adrenocortical carcinoma: are we making progress?

Fetched: September 8th, 2021, 5:00am GMT by Barbara Kiesewetter

Ther Adv Med Oncol. 2021 Aug 31;13:17588359211038409. doi: 10.1177/17588359211038409. eCollection 2021.

ABSTRACT

Adrenocortical carcinoma (ACC) is a rare malignancy characterized by aggressive biology and potential endocrine activity. Surgery can offer cure for localized disease but more than half of patients relapse and primary unresectable or metastasized disease is frequent. Prognosis of metastatic ACC is still limited, with less than 15% of patients alive at 5 years. Recent advances in understanding the molecular profile of ACC underline the high complexity of this disease, which is characterized by limited drugable molecular targets as well as by a complex interplay between a yet scarcely understood microenvironment and potential endocrine activity. Particularly steroid-excess further complicates therapeutic concepts such as immunotherapy, which have markedly improved outcome in other disease entities. To date, mitotane remains the only approved drug for adjuvant and palliative care in ACC. Standard chemotherapy-based protocols with cisplatin, doxorubicin and etoposide offer only marginal improvement in long-term outcome and the number of clinical trials conducted is low due to the rarity of the disease. In the current review, we summarize principles of oncological management for ACC from localized to advanced disease and discuss novel therapeutic strategies, including targeted therapies such as tyrosine kinase inhibitors and antibodies, immunotherapy with a focus on checkpoint inhibitors, individualized treatment concepts based on molecular characterization by next generation sequencing methods, the role of theranostics and evolvement of adjuvant therapy.

PMID:34484430 | PMC:PMC8411624 | DOI:10.1177/17588359211038409

Impact of postoperative radiotherapy on the outcomes of resected adrenocortical carcinoma-a real-world, population-based study

Fetched: September 4th, 2021, 5:00am GMT by Omar Abdel-Rahman

Strahlenther Onkol. 2021 Sep 2. doi: 10.1007/s00066-021-01838-6. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the impact of postoperative radiotherapy on the outcomes of resected adrenocortical carcinoma in a real-world setting.

CONCLUSION: Postoperative radiotherapy following resection of adrenocortical carcinoma is associated with better overall and cancer-specific survival.

PMID:34476529 | DOI:10.1007/s00066-021-01838-6

Telomeric zinc-finger associated protein (TZAP) in cancer biology: friend or foe?

Fetched: September 4th, 2021, 5:00am GMT by Gabriel Arantes Dos Santos

Mol Biol Res Commun. 2021 Sep;10(3):121-129. doi: 10.22099/mbrc.2021.40106.1607.

ABSTRACT

The new identified protein telomeric zinc-finger associated protein (TZAP) is a negative regulator of telomere length. Since telomere length and telomere maintenance mechanisms are essential to cancer progression, TZAP is considered a new player in cancer biology. Here we aimed to analyze TZAP using the Cancer Genome Atlas data in a Pan-Cancer approach. We gathering data from TCGA Pan-Cancer studies utilizing cBioPortal, GEPIA and UALCAN. In total we analyzed 33 types of cancer (n=9664) and their respective controls (n=711). TZAP is transcribed in all cancers but less than 5% of all tumors show any somatic changes. TZAP was downregulated in kidney chromophobe carcinoma, and upregulated in esophageal cancer, head and neck squamous cell carcinomas, kidney renal clear cell carcinoma and in liver hepatocellular carcinoma. Globally, TZAP expression is related to favorable prognosis, associated to better overall and disease-free survival. Looking to specific tumors, TZAP expression has a dual behavior. Its downregulation is associated with poor prognosis in cervical squamous cell carcinoma, in kidney renal clear cell carcinoma, kidney papillary cell carcinoma, lung adenocarcinoma and pancreas adenocarcinoma. On the contrary, in adrenocortical carcinoma, colon and rectal cancer, brain lower grade glioma and prostate adenocarcinoma the upregulation of TZAP is related with poor prognosis. TZAP expression has a positive correlation with TRF1 and TRF2 in normal tissue but not in cancer. Our analyses indicate that TZAP has an important role in oncology and may be considered as a potential biomarker.

PMID:34476265 | PMC:PMC8340314 | DOI:10.22099/mbrc.2021.40106.1607

The molecular feature of macrophages in tumor immune microenvironment of glioma patients

Fetched: September 4th, 2021, 5:00am GMT by Hao Zhang

Comput Struct Biotechnol J. 2021 Aug 14;19:4603-4618. doi: 10.1016/j.csbj.2021.08.019. eCollection 2021.

ABSTRACT

BACKGROUND: Gliomas are one of the most common types of primary tumors in central nervous system. Previous studies have found that macrophages actively participate in tumor growth.

METHODS: Weighted gene co-expression network analysis was used to identify meaningful macrophage-related gene genes for clustering. Pamr, SVM, and neural network were applied for validating clustering results. Somatic mutation and methylation were used for defining the features of identified clusters. Differentially expressed genes (DEGs) between the stratified groups after performing elastic regression and principal component analyses were used for the construction of MScores. The expression of macrophage-specific genes were evaluated in tumor microenvironment based on single cell sequencing analysis. A total of 2365 samples from 15 glioma datasets and 5842 pan-cancer samples were used for external validation of MScore.

RESULTS: Macrophages were identified to be negatively associated with the survival of glioma patients. Twenty-six macrophage-specific DEGs obtained by elastic regression and PCA were highly expressed in macrophages at single-cell level. The prognostic value of MScores in glioma was validated by the active proinflammatory and metabolic profile of infiltrating microenvironment and response to immunotherapies of samples with this signature. MScores managed to stratify patient survival probabilities in 15 external glioma datasets and pan-cancer datasets, which predicted worse survival outcome. Sequencing data and immunohistochemistry of Xiangya glioma cohort confirmed the prognostic value of MScores. A prognostic model based on MScores demonstrated high accuracy rate.

CONCLUSION: Our findings strongly support a modulatory role of macrophages, especially M2 macrophages in glioma progression and warrants further experimental studies.

PMID:34471502 | PMC:PMC8383063 | DOI:10.1016/j.csbj.2021.08.019

Clinical management and outcomes associated with etoposide, doxorubicin, and cisplatin plus mitotane treatment in metastatic adrenocortical carcinoma: a single institute experience

Fetched: September 2nd, 2021, 5:00am GMT by Masaki Uchihara

Int J Clin Oncol. 2021 Sep 1. doi: 10.1007/s10147-021-02021-8. Online ahead of print.

ABSTRACT

PMID:34468885 | DOI:10.1007/s10147-021-02021-8

SMARCA4-Deficient Undifferentiated Tumor Diagnosed on Adrenal Sampling

Fetched: September 1st, 2021, 5:00am GMT by Salam Ashour

Am J Clin Pathol. 2021 Aug 31:aqab101. doi: 10.1093/ajcp/aqab101. Online ahead of print.

ABSTRACT

OBJECTIVES: SMARCA4-deficient undifferentiated tumor has distinct clinicopathologic features. We describe our experience with primary diagnosis on adrenal sampling.

PMID:34463317 | DOI:10.1093/ajcp/aqab101

Permalink for 'Association between preoperative serum albumin and prognosis in patients with adrenocortical carcinoma after primary resection: a retrospective study'

Association between preoperative serum albumin and prognosis in patients with adrenocortical carcinoma after primary resection: a retrospective study

Fetched: August 29th, 2021, 5:00am GMT by Fuxun Zhang

BMC Cancer. 2021 Aug 26;21(1):961. doi: 10.1186/s12885-021-08689-5.

ABSTRACT

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with a poor prognosis. Given the limited treatment options, prognostic assessment of ACC is increasingly crucial. In this study, we aim to assess the correlation between preoperative serum albumin and prognosis in patients with ACC after primary resection.

METHODS: We retrospectively collected and reviewed medical information about 71 ACC patients who underwent primary resection. Survival analysis was performed by Kaplan-Meier analysis with log-rank test or Breslow test. Receiver operating characteristic (ROC) curve and Jordan index was generated to explore optimal cut-off value of albumin. Univariate and multivariate analysis was conducted using Cox's hazards model. Statistical significance was defined as P < 0.05.

RESULTS: Among included patients, 33 patients (46.5%) relapsed at the end of follow-up, while 39 patients (54.9%) died. The median overall survival (OS) of included patients was 17 (range 1-104) months, and median recurrence-free survival (RFS) was 10 (range 0-104) months. In univariate analysis, the albumin was significantly associated with OS (HR:0.491, 95% CI: 0.260-0.930, P = 0.029) and RFS (HR: 0.383, 95% CI: 0.192-0.766, P = 0.007). In multivariate analysis, serum albumin as an independent prognostic factor of OS was confirmed (HR: 0.351, 95% CI: 0.126-0.982, P = 0.046).

CONCLUSIONS: Preoperative albumin might be a significant prognostic factor for ACC patients after primary resection. This result may be useful for risk stratification and management of this rare malignancy.

PMID:34445989 | PMC:PMC8393459 | DOI:10.1186/s12885-021-08689-5

Surgical Management of Adrenocortical Carcinoma: Current Highlights

Fetched: August 29th, 2021, 5:00am GMT by Giuseppe Cavallaro

Biomedicines. 2021 Jul 28;9(8):909. doi: 10.3390/biomedicines9080909.

ABSTRACT

PMID:34440112 | PMC:PMC8389566 | DOI:10.3390/biomedicines9080909

Molecular Mechanisms of Functional Adrenocortical Adenoma and Carcinoma: Genetic Characterization and Intracellular Signaling Pathway

Fetched: August 29th, 2021, 5:00am GMT by Hiroki Shimada

Biomedicines. 2021 Jul 26;9(8):892. doi: 10.3390/biomedicines9080892.

ABSTRACT

PMID:34440096 | PMC:PMC8389593 | DOI:10.3390/biomedicines9080892

Novel Insights into the Molecular Regulation of Ribonucleotide Reductase in Adrenocortical Carcinoma Treatment

Fetched: August 29th, 2021, 5:00am GMT by Christina Bothou

Cancers (Basel). 2021 Aug 20;13(16):4200. doi: 10.3390/cancers13164200.

ABSTRACT

Current systemic treatment options for patients with adrenocortical carcinomas (ACCs) are far from being satisfactory. DNA damage/repair mechanisms, which involve, e.g., ataxia-telangiectasia-mutated (ATM) and ataxia-telangiectasia/Rad3-related (ATR) protein signaling or ribonucleotide reductase subunits M1/M2 (RRM1/RRM2)-encoded ribonucleotide reductase (RNR) activation, commonly contribute to drug resistance. Moreover, the regulation of RRM2b, the p53-induced alternative to RRM2, is of unclear importance for ACC. Upon extensive drug screening, including a large panel of chemotherapies and molecular targeted inhibitors, we provide strong evidence for the anti-tumoral efficacy of combined gemcitabine (G) and cisplatin (C) treatment against the adrenocortical cell lines NCI-H295R and MUC-1. However, accompanying induction of RRM1, RRM2, and RRM2b expression also indicated developing G resistance, a frequent side effect in clinical patient care. Interestingly, this effect was partially reversed upon addition of C. We confirmed our findings for RRM2 protein, RNR-dependent dATP levels, and modulations of related ATM/ATR signaling. Finally, we screened for complementing inhibitors of the DNA damage/repair system targeting RNR, Wee1, CHK1/2, ATR, and ATM. Notably, the combination of G, C, and the dual RRM1/RRM2 inhibitor COH29 resulted in previously unreached total cell killing. In summary, we provide evidence that RNR-modulating therapies might represent a new therapeutic option for ACC.

PMID:34439352 | PMC:PMC8391410 | DOI:10.3390/cancers13164200

Permalink for 'Nomograms for Individualized Evaluation of Prognosis in Adrenocortical Carcinomas for the Elderly: A Population-Based Analysis'

Nomograms for Individualized Evaluation of Prognosis in Adrenocortical Carcinomas for the Elderly: A Population-Based Analysis

Fetched: August 27th, 2021, 5:00am GMT by Weixi Wang

J Invest Surg. 2021 Aug 25:1-8. doi: 10.1080/08941939.2021.1968981. Online ahead of print.

ABSTRACT

BACKGROUND: Adrenocortical carcinoma (ACC) is extremely rare in elderly patients. Thus, this study aimed to identify the incidence rate and develop nomogram models for predicting survival in elderly ACC patients.

METHODS: Data of ACC patients aged >60 years from 1975 to 2016 were obtained from the Surveillance, Epidemiology, and End Results dataset. The national incidence rate was estimated, and survival was subjected to Kaplan-Meier analysis. A multivariate Cox regression model was used to identify predictors of survival. Nomograms were generated to predict survival, calibrated and internally validated.

RESULTS: We identified 583 cases. Univariate analysis showed that patients with younger age (≤67 years), female sex, lower tumor grade, surgical treatment performed, and earlier European Network for the Study of Adrenal Tumors (ENSAT) stage had a better survival (P < 0.05). In the Cox regression analysis, no surgery performed (hazard ratio [HR]: 3.544, 95% CI: 1.142-10.995, P = 0.029 for overall survival [OS]; HR: 3.230, 95% CI: 1.040-10.034, P = 0.043 for disease-specific survival [DSS]) and advanced ENSAT stage (HR: 3.328, 95% CI: 1.628-6.801, P = 0.001 for OS; HR: 3.701, 95% CI: 1.682-8.141, P = 0.001 for DSS) were associated with worse outcomes. Age, sex, histologic grade, surgical resection, radiotherapy, and ENSAT stage were included in the nomograms, with a C-index of 0.692 for OS and 0.694 for DSS, demonstrating a good accuracy in predicting survival.

CONCLUSIONS: This study is the largest review of ACC in elderly patients. We present nomograms to predict survival in elderly ACC patients using clinicopathologic data, which could aid in accurate clinical decision-making.

PMID:34433351 | DOI:10.1080/08941939.2021.1968981

Adrenal biopsy, as a diagnostic method, is associated with decreased overall survival in patients with T1/T2 adrenocortical carcinoma: A propensity score-matched analysis

Fetched: August 25th, 2021, 5:00am GMT by Samer A Naffouje

J Surg Oncol. 2021 Aug 23. doi: 10.1002/jso.26639. Online ahead of print.

ABSTRACT

CONCLUSION: BD in T1/T2 ACC could be associated with disease upstaging and worse OS outcomes.

PMID:34424540 | DOI:10.1002/jso.26639

Targeted genomic analysis of 364 adrenocortical carcinomas

Fetched: August 20th, 2021, 5:00am GMT by Nikita Pozdeyev

Endocr Relat Cancer. 2021 Aug 16;28(10):671-681. doi: 10.1530/ERC-21-0040.

ABSTRACT

Despite recent advances in elucidating molecular pathways underlying adrenocortical carcinoma (ACC), this orphan malignancy is associated with poor survival. Identification of targetable genomic alterations is critical to improve outcomes. The objective of this study was to characterize the genomic profile of a large cohort of patient ACC samples to identify actionable genomic alterations. Three hundred sixty-four individual patient ACC tumors were analyzed. The median age of the cohort was 52 years and 60.9% (n = 222) were female. ACC samples had common alterations in epigenetic pathways with 38% of tumors carrying alterations in genes involved in histone modification, 21% in telomere lengthening, and 21% in SWI/SNF complex. Tumor suppressor genes and WNT signaling pathway were each mutated in 51% of tumors. Fifty (13.7%) ACC tumors had a genomic alteration in genes involved in the DNA mismatch repair (MMR) pathway with many tumors also displaying an unusually high number of mutations and a corresponding MMR mutation signature. In addition, genomic alterations in several genes not previously associated with ACC were observed, including IL7R, LRP1B, FRS2 mutated in 6, 8 and 4% of tumors, respectively. In total, 58.5% of ACC (n = 213) had at least one potentially actionable genomic alteration in 46 different genes. As more than half of ACC have one or more potentially actionable genomic alterations, this highlights the value of targeted sequencing for this orphan cancer with a poor prognosis. In addition, significant incidence of MMR gene alterations suggests that immunotherapy is a promising therapeutic for a considerable subset of ACC patients.

PMID:34410225 | PMC:PMC8384129 | DOI:10.1530/ERC-21-0040

Adjuvant platinum-based chemotherapy in radically resected adrenocortical carcinoma: a cohort study

Fetched: August 18th, 2021, 5:00am GMT by Otilia Kimpel

Br J Cancer. 2021 Aug 16. doi: 10.1038/s41416-021-01513-8. Online ahead of print.

ABSTRACT

BACKGROUND: After radical resection, patients with adrenocortical carcinoma (ACC) frequently experience recurrence and, therefore, effective adjuvant treatment is urgently needed. The aim of the study was to investigate the role of adjuvant platinum-based therapy.

METHODS: In this retrospective multicentre cohort study, we identified patients treated with adjuvant platinum-based chemotherapy after radical resection and compared them with patients without adjuvant chemotherapy. Recurrence-free and overall survival (RFS/OS) were investigated in a matched group analysis and by applying a propensity score matching using the full control cohort (n = 268). For both approaches, we accounted for immortal time bias.

RESULTS: Of the 31 patients in the platinum cohort (R0 n = 25, RX n = 4, R1 n = 2; ENSAT Stage II n = 11, III n = 16, IV n = 4, median Ki67 30%, mitotane n = 28), 14 experienced recurrence compared to 29 of 31 matched controls (median RFS after the landmark at 3 months 17.3 vs. 7.3 months; adjusted HR 0.19 (95% CI 0.09-0.42; P < 0.001). Using propensity score matching, the HR for RFS was 0.45 (0.29-0.89, P = 0.021) and for OS 0.25 (0.09-0.69; P = 0.007).

CONCLUSIONS: Our study provides the first evidence that adjuvant platinum-based chemotherapy may be associated with prolonged recurrence-free and overall survival in patients with ACC and a very high risk for recurrence.

PMID:34400803 | DOI:10.1038/s41416-021-01513-8

Young Woman with Abdominal Pain and Hirsutism

Fetched: August 17th, 2021, 5:00am GMT by Daniel O Hernandez

Ann Emerg Med. 2021 Jul;78(1):e7-e8. doi: 10.1016/j.annemergmed.2021.01.025.

NO ABSTRACT

PMID:34167742 | DOI:10.1016/j.annemergmed.2021.01.025

Feminizing Adrenocortical Tumors as a Rare Etiology of Iso/Contrasexual Pseudopuberty

Fetched: August 13th, 2021, 5:00am GMT by Dogus Vuralli

J Clin Res Pediatr Endocrinol. 2021 Aug 12. doi: 10.4274/jcrpe.galenos.2021.2021.0170. Online ahead of print.

ABSTRACT

OBJECTIVES: Estrogen secreting adrenocortical tumors (ACTs) are quite rare, feminizing adrenocortical tumors (FATs) accounting for 0.37-2% of all ACTs. Present study aims to evaluate clinical and hormonal characteristics as well as treatment options and follow-up of FATs in pediatric age group.

METHODS: We reviewed medical records of 25 children with ACTs in our unit in last two decades. We reported two new pediatric cases of FAT, one benign and the other malignant, in two genders with different clinical presentations. Literature review revealed 34 pediatric patients (22boys) with FAT among 192 articles identified in pubmed database.

RESULTS: FATs are extremely rare tumors that are most commonly seen in men and boys presenting with gynecomastia. FATs are more common in children ≤8 years of age, with a median age at diagnosis of 6 years. While boys present with contrasexual pseudopuberty signs, girls present with isosexual pseudopuberty. High estrogen level strongly supports diagnosis, while elevations in other adrenal hormones may be seen. FATs are usually malignant in adults whereas in children approximately half are benign. Assessment of malignant potential depends on clinical behavior of tumor in children. Although complete surgical resection of benign FATs is thought to be curative, long-term follow-up is required because of unpredictability of these tumors. Prognosis is generally very poor in adult males. FATs in childhood may carry a better prognosis with most of FATs in children are followed without recurrence of tumor.

CONCLUSIONS: FATs are more common in children ≤8 years of age, with a median age at diagnosis of 6 years. FATs in childhood period may carry a better prognosis than in adult males.

PMID:34380293 | DOI:10.4274/jcrpe.galenos.2021.2021.0170

Cancer Stemness Associated With Prognosis and the Efficacy of Immunotherapy in Adrenocortical Carcinoma

Fetched: August 10th, 2021, 5:00am GMT by Xiaoxi Shi

Front Oncol. 2021 Jul 21;11:651622. doi: 10.3389/fonc.2021.651622. eCollection 2021.

ABSTRACT

BACKGROUND: Cancer stem cells (CSCs) have been proven to influence drug resistance, recurrence, and metastasis in tumors. Our study aimed to identify stemness-related prognostic biomarkers for new therapeutic strategies in adrenocortical carcinoma.

METHODS: RNA-seq data and clinical characteristics were downloaded from The Cancer Genome Atlas (TCGA). The stemness indexes, mDNAsi and mRNAsi, were calculated to classify all samples into low-score and high-score groups. Two algorithms, based on the R language, ESTIMATE and single-sample Gene Set Enrichment Analysis (ssGSEA) were used to assess the immune cell infiltration states of adrenocortical carcinoma patients. Weighted Gene Co-expression Network Analysis (WGCNA) was used to find genes that were related to the stemness of cancer. By bioinformatics methods, the correlations between biomarkers capable of predicting immune checkpoint inhibitors (ICIs) responses and stemness of cancer were explored.

RESULTS: High-mRNAsi predicted shorter overall survival (OS) and a higher metastatic trend in adrenocortical carcinoma (ACC) patients. Compared with the low-mRNAsi group, the high-mRNAsi group had a lower ImmuneScore and StromalScroe. Twenty-two stemness-related prognostic genes were obtained by WGCNA, which focused on the function of the cell cycle and cell mitosis. Immune cell infiltration, especially CD8+T cell, increased in the low-mRNAsi group compared with the high-mRNAsi group. Lower expression of PD-L1, CTLA-4, and TIGHT was evaluated in the high-mRNAsi group.

CONCLUSIONS: ACC patients with high-mRNAsi have poor prognosis and less immune cell infiltration. Combined with the finding of lower expression of CTLA-4, TIGHT, and PD-L1 in the high-mRNAsi group, we came to the conclusion that stemness index is a potential biomarker to predict the effectiveness of ICIs.

PMID:34367952 | PMC:PMC8334864 | DOI:10.3389/fonc.2021.651622

Nucleobindin-2/Nesfatin-1-A New Cancer Related Molecule?

Fetched: August 8th, 2021, 5:00am GMT by Alicja M Kmiecik

Int J Mol Sci. 2021 Aug 2;22(15):8313. doi: 10.3390/ijms22158313.

ABSTRACT

Cancer is a heterogeneous disease, and even tumors with similar clinicopathological characteristics show different biology, behavior, and treatment responses. As a result, there is an urgent need to define new prognostic and predictive markers to make treatment options more personalized. According to the latest findings, nucleobindin-2/nesfatin-1 (NUCB2/NESF-1) is an important factor in cancer development and progression. Nucleobindin-2 is a precursor protein of nesfatin-1. As NUCB2 and nesfatin-1 are colocalized in each tissue, their expression is often analyzed together as NUCB2. The metabolic function of NUCB2/NESF-1 is related to food intake, glucose metabolism, and the regulation of immune, cardiovascular and endocrine systems. Recently, it has been demonstrated that high expression of NUCB2/NESF-1 is associated with poor outcomes and promotes cell proliferation, migration, and invasion in, e.g., breast, colon, prostate, endometrial, thyroid, bladder cancers, or glioblastoma. Interestingly, nesfatin-1 is also considered an inhibitor of the proliferation of human adrenocortical carcinoma and ovarian epithelial carcinoma cells. These conflicting results make NUCB2/NESF-1 an interesting target of study in the context of cancer progression. The present review is the first to describe NUCB2/NESF-1 as a new prognostic and predictive marker in cancers.

PMID:34361082 | PMC:PMC8348729 | DOI:10.3390/ijms22158313

Identification of novel lipid metabolic biomarkers associated with poor adrenocortical carcinoma prognosis using integrated bioinformatics

Fetched: August 7th, 2021, 5:00am GMT by Chitra Subramanian

Surgery. 2021 Aug 2:S0039-6060(21)00554-7. doi: 10.1016/j.surg.2021.04.049. Online ahead of print.

ABSTRACT

PMID:34353633 | DOI:10.1016/j.surg.2021.04.049

Adrenocortical carcinoma: current state of the art, ongoing controversies, and future directions in diagnosis and treatment

Fetched: August 6th, 2021, 5:00am GMT by Omair A Shariq

Ther Adv Chronic Dis. 2021 Jul 20;12:20406223211033103. doi: 10.1177/20406223211033103. eCollection 2021.

ABSTRACT

Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy with an annual incidence of ~1 case per million population. Differentiating between ACC and benign adrenocortical tumors can be challenging in patients who present with an incidentally discovered adrenal mass, due to the limited specificity of standard diagnostic imaging. Recently, urine steroid metabolite profiling has been prospectively validated as a novel diagnostic tool for the detection of malignancy with improved accuracy over current modalities. Surgery represents the only curative treatment for ACC, although local recurrence and metastases are common, even after a margin-negative resection is performed. Unlike other intra-abdominal cancers, the role of minimally invasive surgery and lymphadenectomy in ACC is controversial. Adjuvant therapy with the adrenolytic drug mitotane is used to reduce the risk of recurrence after surgery, although evidence supporting its efficacy is limited; it is also currently unclear whether all patients or a subset with the highest risk of recurrence should receive this treatment. Large-scale pan-genomic studies have yielded insights into the pathogenesis of ACC and have defined distinct molecular signatures associated with clinical outcomes that may be used to improve prognostication. For patients with advanced ACC, palliative combination chemotherapy with mitotane is the current standard of care; however, this is associated with poor response rates (RR). Knowledge from molecular profiling studies has been used to guide the development of novel targeted therapies; however, these have shown limited efficacy in early phase trials. As a result, there is an urgent unmet need for more effective therapies for patients with this devastating disease.

PMID:34349894 | PMC:PMC8295938 | DOI:10.1177/20406223211033103

Haemolytic anaemia induced by flutamide: a case report

Fetched: August 4th, 2021, 5:00am GMT by Yu Sun

Eur J Hosp Pharm. 2021 Aug 2:ejhpharm-2021-002936. doi: 10.1136/ejhpharm-2021-002936. Online ahead of print.

ABSTRACT

Flutamide-induced haemolytic anaemia is rare but can be fatal. We describe the case of an 88-year-old man with prostatic carcinoma who, in addition to clinically obvious jaundice, developed haemolytic anaemia after undergoing treatment with flutamide for 5 days. When flutamide was replaced with temporary adrenocortical hormone treatment and blood transfusion, the blood indices and liver function of the patient improved gradually. We emphasise the need for routine monitoring of blood counts for patients undergoing flutamide treatment, and highlight the importance of discontinuing flutamide immediately when haemolytic anaemia occurs.

PMID:34341002 | DOI:10.1136/ejhpharm-2021-002936

Sarcopenia is Associated with Reduced Survival following Surgery for Adrenocortical Carcinoma

Fetched: August 4th, 2021, 5:00am GMT by Mechteld C de Jong

Endocr Res. 2021 Aug 3:1-10. doi: 10.1080/07435800.2021.1954942. Online ahead of print.

ABSTRACT

AIM: Adrenocortical cancer (ACC) is an aggressive malignancy and robust prognostic factors remain unclear. The presence of sarcopenia has been shown to negatively impact survival for other malignancies, but has not been extensively analyzed in ACC.

METHODS: Patients who underwent resection of their ACC between 2010 and 2020 were identified; therapeutic, operative, and outcome data were analyzed. Sarcopenia was assessed by calculation of the skeletal muscle index (SMI) and was defined as an SMI <52.4cm²/m² for males and <38.5cm²/m² for females.

RESULTS: Data on 35 patients (18 F: 17 M; median age 54 [range: 18-86]) who had primary surgical treatment were analyzed. Median tumor size was 10 cm [range:3-15]. In eleven patients (31%), the tumor was hormonally active (cortisol = 8;23%). Seventeen patients (49%) were classified as having sarcopenia on their pre-operative CT scan. The Intraclass Correlation Coefficient (ICC) for intra- and inter-observer variability showed very good agreement (0.99 and 0.98). There was no difference in incidence of sarcopenia stratifying for sex, BMI, or tumor-size, but incidence was higher with increasing age (p < .05). Overall median survival was 36 months, with 1- and 3-year survival rates of 77% and 52%. The presence of sarcopenia was strongly associated with a shorter overall survival (HR = 3.21; [95%CI: 1.06-9.69];p = .03) on unadjusted analyses. Moreover, age, higher T-stage, and presence of capsular invasion were also associated with poorer survival on univariable analyses.

CONCLUSION: The presence of sarcopenia in patients undergoing surgery for ACC could be a predictor of reduced overall survival, although replications of these analyses should be performed in similar, larger cohorts. Specifically, the influence of a patient's hormonal status on the manifestation of sarcopenia should be further defined.

PMID:34340645 | DOI:10.1080/07435800.2021.1954942

Permalink for 'Identification of a Ferroptosis-Related Signature Associated with Prognosis and Immune Infiltration in Adrenocortical Carcinoma'

Identification of a Ferroptosis-Related Signature Associated with Prognosis and Immune Infiltration in Adrenocortical Carcinoma

Fetched: August 3rd, 2021, 5:00am GMT by Xi Chen

Int J Endocrinol. 2021 Jul 20;2021:4654302. doi: 10.1155/2021/4654302. eCollection 2021.

ABSTRACT

Adrenocortical carcinoma (ACC) is a rare malignant tumor with poor prognosis. Ferroptosis, a new form of cell death, differs from other forms of cell death and plays a vital role in tumor progress. Our study aimed to establish a ferroptosis-related signature with prognostic value in ACC. RNA-seq data and corresponding clinical characteristics for ACC were downloaded from TCGA and GEO databases. Genes included in ferroptosis risk signature were assessed by univariable and multivariable Cox regression analysis as well as lasso regression analysis. The prognostic value of the ferroptosis risk signature was assessed using K-M and ROC curves. Furthermore, we performed GSEA to discover the enriched gene sets in high-risk group. Additionally, TIMER website was applied to detect a possible connection between the signature and immune cells infiltration. ssGSEA was performed to evaluate scores of immune cells and immune-related pathways in two groups. A ferroptosis signature comprised of six genes (SLC7A11, TP53, HELLS, ACSL4, PCBP2, and HMGB1) was constructed to predict prognosis and reflect the immune infiltration in ACC. Patients in high-risk group were inclined to have worse prognosis. The ferroptosis model performed well in predicting prognosis and could be served as an independent indicator in ACC. GSEA revealed that gene sets correlated with biological processes including cell cycle, DNA replication, base excision repair, and P53 signaling pathway were highly enriched in high-risk group. In addition, we discovered that the expressional levels of hub genes were linked to six immune cells' infiltration in ACC tumor. ssGSEA revealed that contents of most immune cells significantly decreased in the high-risk group. In conclusion, the novel ferroptosis risk signature could be useful in predicting prognosis and reflecting immune infiltration in ACC. It also brings us new insights into the possible value of targeting ferroptosis during the therapy of ACC.

PMID:34335745 | PMC:PMC8318759 | DOI:10.1155/2021/4654302

The Herbicide Atrazine Potentiates Angiotensin II-Induced Aldosterone Synthesis and Release From Adrenal Cells

Fetched: August 3rd, 2021, 5:00am GMT by Arthur D Zimmerman

Front Endocrinol (Lausanne). 2021 Jul 14;12:697505. doi: 10.3389/fendo.2021.697505. eCollection 2021.

ABSTRACT

Atrazine is one of the most commonly used pre-emergence and early post-emergence herbicides in the world. We have shown previously that atrazine does not directly stimulate the pituitary or adrenal to trigger hormone release but acts centrally to activate a stress-like activation of the hypothalamic-pituitary-adrenal axis. In doing so, atrazine treatment has been shown to cause adrenal morphology changes characteristic of repeated stress. In this study, adrenals from atrazine treated and stressed animals were directly compared after 4 days of atrazine treatment or restraint stress. Both atrazine and stressed animals displayed reduced adrenocortical zona glomerulosa thickness and aldosterone synthase (CYP11B2) expression, indicative of repeated adrenal stimulation by adrenocorticotropic hormone. To determine if reduced CYP11B2 expression resulted in attenuated aldosterone synthesis, stressed and atrazine treated animals were challenged with angiotensin II (Ang II). As predicted, stressed animals produced less aldosterone compared to control animals when stimulated. However, atrazine treated animals had higher circulating aldosterone concentrations compared to both stressed and control groups. Ang II-induced aldosterone release was also potentiated in atrazine pretreated human adrenocortical carcinoma cells (H295R). Atrazine pretreated did not alter the expression of the rate limiting steroidogenic StAR protein or angiotensin II receptor 1. Atrazine treated animals also presented with higher basal blood pressure than vehicle treated control animals suggesting sustained elevations in circulating aldosterone levels. Our results demonstrate that treatment with the widely used herbicide, atrazine, directly increases stimulated production of aldosterone in adrenocortical cells independent of expression changes to rate limiting steroidogenic enzymes.

PMID:34335472 | PMC:PMC8317615 | DOI:10.3389/fendo.2021.697505

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