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Pancreas 2018
Review
Topics: Animals; Disease Models, Animal; Genetic Predisposition to Disease; Humans; Mice; Mutation; Neoplastic Syndromes, Hereditary; Neuroendocrine Tumors; Pancreatic Neoplasms; Receptors, Glucagon
PubMed: 29702528
DOI: 10.1097/MPA.0000000000001044 -
The New England Journal of Medicine Nov 2023
Topics: Humans; Liver; Liver Transplantation; Metabolism, Inborn Errors; Neoplastic Syndromes, Hereditary; Rare Diseases; Glucagon
PubMed: 37991861
DOI: 10.1056/NEJMe2310332 -
Journal of Gastroenterology and... Aug 2023
Review
Topics: Humans; Glucagon; Mutation; Pancreatic Neoplasms
PubMed: 36698259
DOI: 10.1111/jgh.16104 -
The New England Journal of Medicine Nov 2023Mahvash disease is an exceedingly rare genetic disorder of glucagon signaling characterized by hyperglucagonemia, hyperaminoacidemia, and pancreatic α-cell hyperplasia....
Mahvash disease is an exceedingly rare genetic disorder of glucagon signaling characterized by hyperglucagonemia, hyperaminoacidemia, and pancreatic α-cell hyperplasia. Although there is no known definitive treatment, octreotide has been used to decrease systemic glucagon levels. We describe a woman who presented to our medical center after three episodes of small-volume hematemesis. She was found to have hyperglucagonemia and pancreatic hypertrophy with genetically confirmed Mahvash disease and also had evidence of portal hypertension (recurrent portosystemic encephalopathy and variceal hemorrhage) in the absence of cirrhosis. These findings established a diagnosis of portosinusoidal vascular disease, a presinusoidal type of portal hypertension previously known as noncirrhotic portal hypertension. Liver transplantation was followed by normalization of serum glucagon and ammonia levels, reversal of pancreatic hypertrophy, and resolution of recurrent encephalopathy and bleeding varices.
Topics: Female; Humans; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Glucagon; Hypertension, Portal; Hypertrophy; Liver Cirrhosis; Liver Transplantation; Genetic Diseases, Inborn; Pancreatic Diseases; Glucagon-Secreting Cells
PubMed: 37991855
DOI: 10.1056/NEJMoa2303226 -
The New England Journal of Medicine Dec 2023
PubMed: 38118047
DOI: 10.1056/NEJMx230012 -
The Biochemical Journal Aug 2020The detailed metabolic characterization of the glucagon receptor (Gcgr)V369M+/+ mutant mice described in Lin et al. in the Biochemical Journal is of interest and...
The detailed metabolic characterization of the glucagon receptor (Gcgr)V369M+/+ mutant mice described in Lin et al. in the Biochemical Journal is of interest and resulting in the expected metabolic profile. We would like to point out that these mice might also be extremely useful as a precision medicine model of mild Mahvash disease, a rare hereditary pancreatic neuroendocrine tumor syndrome characterized by inactivating mutations in the glucagon receptor. Further characterization of pancreas morphology and histology in the GcgrV369M+/+ mice at more advanced ages will be critically important to understand mild Mahvash disease in humans.
Topics: Animals; Glucagon; Humans; Metabolic Diseases; Mice; Mutation; Precision Medicine; Receptors, Glucagon
PubMed: 32785645
DOI: 10.1042/BCJ20200522 -
Academic Radiology Nov 2022
Topics: Humans; Neuroendocrine Tumors; Pancreatic Neoplasms; Pancreas; Abdomen; Syndrome
PubMed: 36075823
DOI: 10.1016/j.acra.2022.08.003 -
Academic Radiology Nov 2022
Topics: Humans; Neuroendocrine Tumors; Pancreas; Pancreatic Neoplasms; Abdomen; Syndrome
PubMed: 36180326
DOI: 10.1016/j.acra.2022.08.004 -
Journal of Clinical Oncology : Official... Dec 2021To study the impact of transarterial Yttrium-90 radioembolization (TARE) in combination with second-line systemic chemotherapy for colorectal liver metastases (CLM). (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To study the impact of transarterial Yttrium-90 radioembolization (TARE) in combination with second-line systemic chemotherapy for colorectal liver metastases (CLM).
METHODS
In this international, multicenter, open-label phase III trial, patients with CLM who progressed on oxaliplatin- or irinotecan-based first-line therapy were randomly assigned 1:1 to receive second-line chemotherapy with or without TARE. The two primary end points were progression-free survival (PFS) and hepatic PFS (hPFS), assessed by blinded independent central review. Random assignment was performed using a web- or voice-based system stratified by unilobar or bilobar disease, oxaliplatin- or irinotecan-based first-line chemotherapy, and mutation status.
RESULTS
Four hundred twenty-eight patients from 95 centers in North America, Europe, and Asia were randomly assigned to chemotherapy with or without TARE; this represents the intention-to-treat population and included 215 patients in the TARE plus chemotherapy group and 213 patients in the chemotherapy alone group. The hazard ratio (HR) for PFS was 0.69 (95% CI, 0.54 to 0.88; 1-sided = .0013), with a median PFS of 8.0 (95% CI, 7.2 to 9.2) and 7.2 (95% CI, 5.7 to 7.6) months, respectively. The HR for hPFS was 0.59 (95% CI, 0.46 to 0.77; 1-sided < .0001), with a median hPFS of 9.1 (95% CI, 7.8 to 9.7) and 7.2 (95% CI, 5.7 to 7.6) months, respectively. Objective response rates were 34.0% (95% CI, 28.0 to 40.5) and 21.1% (95% CI, 16.2 to 27.1; 1-sided = .0019) for the TARE and chemotherapy groups, respectively. Median overall survival was 14.0 (95% CI, 11.8 to 15.5) and 14.4 months (95% CI, 12.8 to 16.4; 1-sided = .7229) with a HR of 1.07 (95% CI, 0.86 to 1.32) for TARE and chemotherapy groups, respectively. Grade 3 adverse events were reported more frequently with TARE (68.4% 49.3%). Both groups received full chemotherapy dose intensity.
CONCLUSION
The addition of TARE to systemic therapy for second-line CLM led to longer PFS and hPFS. Further subset analyses are needed to better define the ideal patient population that would benefit from TARE.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Case-Control Studies; Chemoradiotherapy; Colorectal Neoplasms; Embolization, Therapeutic; Female; Follow-Up Studies; Humans; Irinotecan; Liver Neoplasms; Male; Middle Aged; Oxaliplatin; Prognosis; Survival Rate; Yttrium Radioisotopes
PubMed: 34541864
DOI: 10.1200/JCO.21.01839 -
Seminars in Diagnostic Pathology May 2018The identification of at-risk kindreds facilitates screening and risk reduction strategies for patients with hereditary cancer predisposition syndromes. Recently,... (Review)
Review
The identification of at-risk kindreds facilitates screening and risk reduction strategies for patients with hereditary cancer predisposition syndromes. Recently, immunohistochemistry (IHC) has emerged as a cost-effective strategy for detecting or inferring the presence of mutations in both tumors and the germline of patients presenting with tumors associated with hereditary cancer predisposition syndromes. In this review we discuss the use of novel IHC markers, including PRKAR1A, β-catenin, SDHB, fumarate hydratase and 2SC, HRASQ61R, BAP1, parafibromin and glucagon, which have either established applications or show promise for surgical pathologists to complement morphological or clinical suspicion of hereditary cancer predisposition syndromes. Specifically, we focus on Carney complex, familial adenomatous polyposis (FAP)-associated cribriform-morular variant of papillary thyroid carcinoma, familial succinate dehydrogenase-related pheochromocytoma/paraganglioma syndromes, hereditary leiomyomatosis and renal cell cancer (HLRCC), medullary thyroid cancer and Multiple Endocrine Neoplasia 2 (MEN2), BAP1 hereditary cancer predisposition syndrome, Hyperparathyroidism-Jaw Tumor Syndrome (HPT-JT), and Pancreatic Neuroendocrine Tumor Syndrome (Mahvash disease).
Topics: Biomarkers, Tumor; DNA Mutational Analysis; Genetic Predisposition to Disease; Genetic Testing; Heredity; High-Throughput Screening Assays; Humans; Immunohistochemistry; Mutation; Neoplastic Syndromes, Hereditary; Pathology, Molecular; Pedigree; Phenotype; Predictive Value of Tests; Risk Assessment; Risk Factors
PubMed: 28662997
DOI: 10.1053/j.semdp.2017.05.004