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Pancreatic Neoplasms: HELP
Articles by Raghuwansh P. Sah
Based on 5 articles published since 2010
(Why 5 articles?)

Between 2010 and 2020, Raghuwansh Sah wrote the following 5 articles about Pancreatic Neoplasms.
+ Citations + Abstracts
1 Review New insights into pancreatic cancer-induced paraneoplastic diabetes. 2013

Sah, Raghuwansh P / Nagpal, Sajan Jiv Singh / Mukhopadhyay, Debabrata / Chari, Suresh T. ·Department of Internal Medicine, Mayo Clinic, 200 First Street South West, Rochester, MN 55905, USA. ·Nat Rev Gastroenterol Hepatol · Pubmed #23528347.

ABSTRACT: Up to 85% of patients with pancreatic cancer have diabetes or hyperglycaemia, which frequently manifests as early as 2-3 years before a diagnosis of pancreatic cancer. Conversely, patients with new-onset diabetes have a 5-8-fold increased risk of being diagnosed with pancreatic cancer within 1-3 years of developing diabetes. Emerging evidence now indicates that pancreatic cancer causes diabetes. As in type 2 diabetes, β-cell dysfunction and peripheral insulin resistance are seen in pancreatic cancer-induced diabetes. However, unlike in patients with type 2 diabetes, glucose control worsens in patients with pancreatic cancer in the face of ongoing, often profound, weight loss. Diabetes and weight loss, which precede cachexia onset by several months, are paraneoplastic phenomena induced by pancreatic cancer. Although the pathogenesis of these pancreatic cancer-induced metabolic alterations is only beginning to be understood, these are likely mechanisms to promote the survival and growth of pancreatic cancer in a hostile and highly desmoplastic microenvironment. Interestingly, these metabolic changes could enable early diagnosis of pancreatic cancer, if they can be distinguished from the ones that occur in patients with type 2 diabetes. One such possible biomarker is adrenomedullin, which is a potential mediator of β-cell dysfunction in pancreatic cancer-induced diabetes.

2 Clinical Trial Endoscopic retrograde pancreatography criteria to diagnose autoimmune pancreatitis: an international multicentre study. 2011

Sugumar, Aravind / Levy, Michael J / Kamisawa, Terumi / Webster, G J / Kim, Myung-Hwan / Enders, Felicity / Amin, Zahir / Baron, Todd H / Chapman, Mike H / Church, Nicholas I / Clain, Jonathan E / Egawa, Naoto / Johnson, Gavin J / Okazaki, Kazuichi / Pearson, Randall K / Pereira, Stephen P / Petersen, Bret T / Read, Samantha / Sah, Raghuwansh P / Sandanayake, Neomal S / Takahashi, Naoki / Topazian, Mark D / Uchida, Kazushige / Vege, Santhi Swaroop / Chari, Suresh T. ·Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. ·Gut · Pubmed #21131631.

ABSTRACT: BACKGROUND: Characteristic pancreatic duct changes on endoscopic retrograde pancreatography (ERP) have been described in autoimmune pancreatitis (AIP). The performance characteristics of ERP to diagnose AIP were determined. METHODS: The study was done in two phases. In phase I, 21 physicians from four centres in Asia, Europe and the USA, unaware of the clinical data or diagnoses, reviewed 40 preselected ERPs of patients with AIP (n=20), chronic pancreatitis (n=10) and pancreatic cancer (n=10). Physicians noted the presence or absence of key pancreatographic features and ranked the diagnostic possibilities. For phase II, a teaching module was created based on features found most useful in the diagnosis of AIP by the four best performing physicians in phase I. After a washout period of 3 months, all physicians reviewed the teaching module and reanalysed the same set of ERPs, unaware of their performance in phase I. RESULTS: In phase I the sensitivity, specificity and interobserver agreement of ERP alone to diagnose AIP were 44, 92 and 0.23, respectively. The four key features of AIP identified in phase I were (i) long (>1/3 the length of the pancreatic duct) stricture; (ii) lack of upstream dilatation from the stricture (<5 mm); (iii) multiple strictures; and (iv) side branches arising from a strictured segment. In phase II the sensitivity (71%) of ERP significantly improved (p<0.05) without a significant decline in specificity (83%) (p>0.05); the interobserver agreement was fair (0.40). CONCLUSIONS: The ability to diagnose AIP based on ERP features alone is limited but can be improved with knowledge of some key features.

3 Article Phases of Metabolic and Soft Tissue Changes in Months Preceding a Diagnosis of Pancreatic Ductal Adenocarcinoma. 2019

Sah, Raghuwansh P / Sharma, Ayush / Nagpal, Sajan / Patlolla, Sri Harsha / Sharma, Anil / Kandlakunta, Harika / Anani, Vincent / Angom, Ramcharan Singh / Kamboj, Amrit K / Ahmed, Nazir / Mohapatra, Sonmoon / Vivekanandhan, Sneha / Philbrick, Kenneth A / Weston, Alexander / Takahashi, Naoki / Kirkland, James / Javeed, Naureen / Matveyenko, Aleksey / Levy, Michael J / Mukhopadhyay, Debabrata / Chari, Suresh T. ·Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. · Department of Biochemistry and Molecular Biology, Mayo Clinic, Jacksonville, Florida. · Department of Radiology Informatics, Mayo Clinic, Rochester, Minnesota. · Division of Radiology, Mayo Clinic, Rochester, Minnesota. · Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, Minnesota. · Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota. · Department of Biochemistry and Molecular Biology, Mayo Clinic, Jacksonville, Florida. Electronic address: Mukhopadhyay.debabrata@mayo.edu. · Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. Electronic address: Chari.suresh@mayo.edu. ·Gastroenterology · Pubmed #30677401.

ABSTRACT: BACKGROUND & AIMS: Identifying metabolic abnormalities that occur before pancreatic ductal adenocarcinoma (PDAC) diagnosis could increase chances for early detection. We collected data on changes in metabolic parameters (glucose, serum lipids, triglycerides; total, low-density, and high-density cholesterol; and total body weight) and soft tissues (abdominal subcutaneous fat [SAT], adipose tissue, visceral adipose tissue [VAT], and muscle) from patients 5 years before the received a diagnosis of PDAC. METHODS: We collected data from 219 patients with a diagnosis of PDAC (patients) and 657 healthy individuals (controls) from the Rochester Epidemiology Project, from 2000 through 2015. We compared metabolic profiles of patients with those of age- and sex-matched controls, constructing temporal profiles of fasting blood glucose, serum lipids including triglycerides, cholesterol profiles, and body weight and temperature for 60 months before the diagnosis of PDAC (index date). To construct the temporal profile of soft tissue changes, we collected computed tomography scans from 68 patients, comparing baseline (>18 months before diagnosis) areas of SAT, VAT, and muscle at L2/L3 vertebra with those of later scans until time of diagnosis. SAT and VAT, isolated from healthy individuals, were exposed to exosomes isolated from PDAC cell lines and analyzed by RNA sequencing. SAT was collected from KRAS RESULTS: There were no significant differences in metabolic or soft tissue features of patients vs controls until 30 months before PDAC diagnosis. In the 30 to 18 months before PDAC diagnosis (phase 1, hyperglycemia), a significant proportion of patients developed hyperglycemia, compared with controls, without soft tissue changes. In the 18 to 6 months before PDAC diagnosis (phase 2, pre-cachexia), patients had significant increases in hyperglycemia and decreases in serum lipids, body weight, and SAT, with preserved VAT and muscle. In the 6 to 0 months before PDAC diagnosis (phase 3, cachexia), a significant proportion of patients had hyperglycemia compared with controls, and patients had significant reductions in all serum lipids, SAT, VAT, and muscle. We believe the patients had browning of SAT, based on increases in body temperature, starting 18 months before PDAC diagnosis. We observed expression of uncoupling protein 1 (UCP1) in SAT exposed to PDAC exosomes, SAT from mice with PDACs, and SAT from all 5 patients but only 1 of 4 controls. CONCLUSIONS: We identified 3 phases of metabolic and soft tissue changes that precede a diagnosis of PDAC. Loss of SAT starts 18 months before PDAC identification, and is likely due to browning. Overexpression of UCP1 in SAT might be a biomarker of early-stage PDAC, but further studies are needed.

4 Article Fukuoka criteria accurately predict risk for adverse outcomes during follow-up of pancreatic cysts presumed to be intraductal papillary mucinous neoplasms. 2017

Mukewar, Saurabh / de Pretis, Nicolo / Aryal-Khanal, Anupama / Ahmed, Nazir / Sah, Raghuwansh / Enders, Felicity / Larson, Joseph J / Levy, Michael J / Takahashi, Naoki / Topazian, Mark / Pearson, Randall / Vege, Santhi S / Chari, Suresh T. ·Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA. · Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, USA. · Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA. ·Gut · Pubmed #27390303.

ABSTRACT: OBJECTIVE: Fukuoka consensus guidelines classify pancreatic cystic lesions (PCLs) presumed to be intraductal papillary mucinous neoplasms (IPMNs) into Fukuoka positive (FP) (subgroups of high-risk (HR) and worrisome features (WFs)) and Fukuoka negative (FN) (non-HR feature/WF cysts). We retrospectively estimated 5-year risk of pancreatic cancer (PC) in FN, WF and HR cysts of patients with PCL-IPMN. DESIGN: From Mayo Clinic databases, we randomly selected 2000 patients reported to have a PCL; we excluded inflammatory or suspected non-IPMN cysts and those without imaging follow-up. We re-reviewed cross-sectional imaging and abstracted clinical and follow-up data on PCL-IPMNs. The study contained 802 patients with FN cysts and 358 with FP cysts. RESULTS: Patients with PCL-IPMN had median (IQR) follow-up of 4.2 (1.8-7.1) years. Among FN cysts, 5-year PC risk was low (2-3%) regardless of cyst size (p=0.67). After excluding events in the first 6 months, 5-year PC risk remained low (0-2%) regardless of cyst size (p=0.61). Among FP cysts, HR cysts (n=66) had greater 5-year PC risk than WF cysts (n=292) (49.7% vs 4.1%; p<0.001). In HR cysts, 3-year PC risk was greatest for obstructive jaundice versus enhancing solid component or main pancreatic duct >10 mm (79.8% vs 37.3% vs 39.4%, respectively; p=0.01). CONCLUSIONS: Fukuoka guidelines accurately stratify PCL-IPMNs for PC risk, with FN cysts having lowest and HR cysts having greatest risk. After 6-month follow-up, WF and FN cysts had a low 5-year PC risk. Surveillance strategies should be tailored appropriately.

5 Article Pathogenesis of pancreatic cancer exosome-induced lipolysis in adipose tissue. 2016

Sagar, Gunisha / Sah, Raghuwansh P / Javeed, Naureen / Dutta, Shamit K / Smyrk, Thomas C / Lau, Julie S / Giorgadze, Nino / Tchkonia, Tamar / Kirkland, James L / Chari, Suresh T / Mukhopadhyay, Debabrata. ·Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA. · Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA. · Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA. · Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, Minnesota, USA. ·Gut · Pubmed #26061593.

ABSTRACT: BACKGROUND AND OBJECTIVES: New-onset diabetes and concomitant weight loss occurring several months before the clinical presentation of pancreatic cancer (PC) appear to be paraneoplastic phenomena caused by tumour-secreted products. Our recent findings have shown exosomal adrenomedullin (AM) is important in development of diabetes in PC. Adipose tissue lipolysis might explain early onset weight loss in PC. We hypothesise that lipolysis-inducing cargo is carried in exosomes shed by PC and is responsible for the paraneoplastic effects. Therefore, in this study we investigate if exosomes secreted by PC induce lipolysis in adipocytes and explore the role of AM in PC-exosomes as the mediator of this lipolysis. DESIGN: Exosomes from patient-derived cell lines and from plasma of patients with PC and non-PC controls were isolated and characterised. Differentiated murine (3T3-L1) and human adipocytes were exposed to these exosomes to study lipolysis. Glycerol assay and western blotting were used to study lipolysis. Duolink Assay was used to study AM and adrenomedullin receptor (ADMR) interaction in adipocytes treated with exosomes. RESULTS: In murine and human adipocytes, we found that both AM and PC-exosomes promoted lipolysis, which was abrogated by ADMR blockade. AM interacted with its receptor on the adipocytes, activated p38 and extracellular signal-regulated (ERK1/2) mitogen-activated protein kinases and promoted lipolysis by phosphorylating hormone-sensitive lipase. PKH67-labelled PC-exosomes were readily internalised into adipocytes and involved both caveolin and macropinocytosis as possible mechanisms for endocytosis. CONCLUSIONS: PC-secreted exosomes induce lipolysis in subcutaneous adipose tissue; exosomal AM is a candidate mediator of this effect.