Publications by authors named "Shounak Majumder"

73 Publications

Determining age and sex-specific distribution of pancreatic whole-gland CT attenuation using artificial intelligence aided image segmentation: Associations with body composition and pancreatic cancer risk.

Pancreatology 2021 Dec 18;21(8):1524-1530. Epub 2021 Aug 18.

Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA. Electronic address:

Background & Aims: Increased intrapancreatic fat is associated with pancreatic diseases; however, there are no established objective diagnostic criteria for fatty pancreas. On non-contrast computed tomography (CT), adipose tissue shows negative Hounsfield Unit (HU) attenuations (-150 to -30 HU). Using whole organ segmentation on non-contrast CT, we aimed to describe whole gland pancreatic attenuation and establish 5th and 10th percentile thresholds across a spectrum of age and sex. Subsequently, we aimed to evaluate the association between low pancreatic HU and risk of pancreatic ductal adenocarcinoma (PDAC).

Methods: The whole pancreas was segmented in 19,456 images from 469 non-contrast CT scans. A convolutional neural network was trained to assist pancreas segmentation. Mean pancreatic HU, volume, and body composition metrics were calculated. The lower 5th and 10th percentile for mean pancreatic HU were identified, examining the association with age and sex. Pre-diagnostic CT scans from patients who later developed PDAC were compared to cancer-free controls.

Results: Less than 5th percentile mean pancreatic HU was significantly associated with increase in BMI (OR 1.07; 1.03-1.11), visceral fat (OR 1.37; 1.15-1.64), total abdominal fat (OR 1.12; 1.03-1.22), and diabetes mellitus type 1 (OR 6.76; 1.68-27.28). Compared to controls, pre-diagnostic scans in PDAC cases had lower mean whole gland pancreatic HU (-0.2 vs 7.8, p = 0.026).

Conclusion: In this study, we report age and sex-specific distribution of pancreatic whole-gland CT attenuation. Compared to controls, mean whole gland pancreatic HU is significantly lower in the pre-diagnostic phase of PDAC.
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http://dx.doi.org/10.1016/j.pan.2021.08.004DOI Listing
December 2021

Early detection of pancreatic cancer: current state and future opportunities.

Curr Opin Gastroenterol 2021 09;37(5):532-538

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.

Purpose Of Review: Pancreatic ductal adenocarcinoma (PDAC) is third leading cause of cancer death in the United States, a lethal disease with no screening strategy. Although diagnosis at an early stage is associated with improved survival, clinical detection of PDAC is typically at an advanced symptomatic stage when best in class therapies have limited impact on survival.

Recent Findings: In recent years this status quo has been challenged by the identification of novel risk factors, molecular markers of early-stage disease and innovations in pancreatic imaging. There is now expert consensus that screening may be pursued in a cohort of individuals with increased likelihood of developing PDAC based on genetic and familial risk.

Summary: The current review summarizes the known risk factors of PDAC, current knowledge and recent observations pertinent to early detection of PDAC in these risk groups and outlines future approaches that will potentially advance the field.
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http://dx.doi.org/10.1097/MOG.0000000000000770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494382PMC
September 2021

How I Approach Screening for Pancreatic Cancer.

Am J Gastroenterol 2021 08;116(8):1569-1571

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.

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http://dx.doi.org/10.14309/ajg.0000000000001305DOI Listing
August 2021

Risk stratification of pancreatic cysts: a convoluted path to finding the needle in the haystack.

Gastrointest Endosc 2021 07 14;94(1):88-90. Epub 2021 May 14.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.

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http://dx.doi.org/10.1016/j.gie.2021.03.012DOI Listing
July 2021

Predicting the Need for Step-Up Therapy After EUS-Guided Drainage of Pancreatic Fluid Collections With Lumen-Apposing Metal Stents.

Clin Gastroenterol Hepatol 2021 10 2;19(10):2192-2198. Epub 2021 Jun 2.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.

Background & Aims: A significant proportion of individuals with pancreatic fluid collections (PFCs) require step-up therapy after endoscopic drainage with lumen-apposing metal stents. The aim of this study is to identify factors associated with PFCs that require step-up therapy.

Methods: A retrospective cohort study of patients undergoing endoscopic ultrasound-guided drainage of PFCs with lumen-apposing metal stents from April 2014 to October 2019 at a single center was performed. Step-up therapy included direct endoscopic necrosectomy, additional drainage site (endoscopic or percutaneous), or surgical intervention after the initial drainage procedure. Multivariable logistic regression was performed using a backward stepwise approach with a P ≤ .2 threshold for variable retention to identify factors predictive for the need for step-up therapy.

Results: One hundred thirty-six patients were included in the final study cohort, of whom 69 (50.7%) required step-up therapy. Independent predictors of step-up therapy included: collection size measuring ≥10 cm (odds ratio [OR], 8.91; 95% confidence interval [CI], 3.36-23.61), paracolic extension of the PFC (OR, 4.04; 95% CI, 1.60-10.23), and ≥30% solid necrosis (OR, 4.24; 95% CI, 1.48-12.16). In a sensitivity analysis of 81 patients with walled-off necrosis, 51 (63.0%) required step-up therapy. Similarly, factors predictive of the need for step-up therapy for walled-off necrosis included: collection size measuring ≥10 cm (OR, 6.94; 95% CI, 1.76-27.45), paracolic extension of the PFC (OR, 3.79; 95% CI, 1.18-12.14), and ≥30% solid necrosis (OR, 7.10; 95% CI, 1.16-43.48).

Conclusions: Half of all patients with PFCs drained with lumen-apposing metal stents required step-up therapy, most commonly direct endoscopic necrosectomy. Individuals with PFCs ≥10 cm in size, paracolic extension, or ≥30% solid necrosis are more likely to require step-up therapy and should be considered for early endoscopic reintervention.
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http://dx.doi.org/10.1016/j.cgh.2021.05.005DOI Listing
October 2021

Quality gaps in public pancreas imaging datasets: Implications & challenges for AI applications.

Pancreatology 2021 Aug 2;21(5):1001-1008. Epub 2021 Apr 2.

Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. Electronic address:

Objective: Quality gaps in medical imaging datasets lead to profound errors in experiments. Our objective was to characterize such quality gaps in public pancreas imaging datasets (PPIDs), to evaluate their impact on previously published studies, and to provide post-hoc labels and segmentations as a value-add for these PPIDs.

Methods: We scored the available PPIDs on the medical imaging data readiness (MIDaR) scale, and evaluated for associated metadata, image quality, acquisition phase, etiology of pancreas lesion, sources of confounders, and biases. Studies utilizing these PPIDs were evaluated for awareness of and any impact of quality gaps on their results. Volumetric pancreatic adenocarcinoma (PDA) segmentations were performed for non-annotated CTs by a junior radiologist (R1) and reviewed by a senior radiologist (R3).

Results: We found three PPIDs with 560 CTs and six MRIs. NIH dataset of normal pancreas CTs (PCT) (n = 80 CTs) had optimal image quality and met MIDaR A criteria but parts of pancreas have been excluded in the provided segmentations. TCIA-PDA (n = 60 CTs; 6 MRIs) and MSD(n = 420 CTs) datasets categorized to MIDaR B due to incomplete annotations, limited metadata, and insufficient documentation. Substantial proportion of CTs from TCIA-PDA and MSD datasets were found unsuitable for AI due to biliary stents [TCIA-PDA:10 (17%); MSD:112 (27%)] or other factors (non-portal venous phase, suboptimal image quality, non-PDA etiology, or post-treatment status) [TCIA-PDA:5 (8.5%); MSD:156 (37.1%)]. These quality gaps were not accounted for in any of the 25 studies that have used these PPIDs (NIH-PCT:20; MSD:1; both: 4). PDA segmentations were done by R1 in 91 eligible CTs (TCIA-PDA:42; MSD:49). Of these, corrections were made by R3 in 16 CTs (18%) (TCIA-PDA:4; MSD:12) [mean (standard deviation) Dice: 0.72(0.21) and 0.63(0.23) respectively].

Conclusion: Substantial quality gaps, sources of bias, and high proportion of CTs unsuitable for AI characterize the available limited PPIDs. Published studies on these PPIDs do not account for these quality gaps. We complement these PPIDs through post-hoc labels and segmentations for public release on the TCIA portal. Collaborative efforts leading to large, well-curated PPIDs supported by adequate documentation are critically needed to translate the promise of AI to clinical practice.
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http://dx.doi.org/10.1016/j.pan.2021.03.016DOI Listing
August 2021

High Detection Rates of Pancreatic Cancer Across Stages by Plasma Assay of Novel Methylated DNA Markers and CA19-9.

Clin Cancer Res 2021 May 16;27(9):2523-2532. Epub 2021 Feb 16.

Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, Minnesota.

Purpose: We have previously identified tissue methylated DNA markers (MDMs) associated with pancreatic ductal adenocarcinoma (PDAC). In this case-control study, we aimed to assess the diagnostic performance of plasma MDMs for PDAC.

Experimental Design: Thirteen MDMs (, and ) were identified on the basis of selection criteria applied to results of prior tissue experiments and assays were optimized in plasma. Next, 340 plasma samples (170 PDAC cases and 170 controls) were assayed using target enrichment long-probe quantitative amplified signal method. Initially, 120 advanced-stage PDAC cases and 120 healthy controls were used to train a prediction algorithm at 97.5% specificity using random forest modeling. Subsequently, the locked algorithm derived from the training set was applied to an independent blinded test set of 50 early-stage PDAC cases and 50 controls. Finally, data from all 340 patients were combined, and cross-validated.

Results: The cross-validated area under the receiver operating characteristic curve (AUC) for the training set was 0.93 (0.89-0.96) for the MDM panel alone, 0.91 (95% confidence interval, 0.87-0.96) for carbohydrate antigen 19-9 (CA19-9) alone, and 0.99 (0.98-1) for the combined MDM-CA19-9 panel. In the test set of early-stage PDAC, the AUC for MDMs alone was 0.84 (0.76-0.92), CA19-9 alone was 0.87 (0.79-0.94), and combined MDM-CA19-9 panel was 0.90 (0.84-0.97) significantly better compared with either MDMs alone or CA19-9 alone ( = 0.0382 and 0.0490, respectively). At a preset specificity of 97.5%, the sensitivity for the combined panel in the test set was 80% (28%-99%) for stage I disease and 82% (68%-92%) for stage II disease. Using the combined datasets, the cross-validated AUC was 0.9 (0.86-0.94) for the MDM panel alone and 0.89 for CA19-9 alone (0.84-0.93) versus 0.97 (0.94-0.99) for the combined MDM-CA19-9 panel ( ≤ 0.0001). Overall, cross-validated sensitivity of MDM-CA19-9 panel was 92% (83%-98%), with an observed specificity of 92% at the preset specificity of 97.5%.

Conclusions: Plasma MDMs in combination with CA19-9 detect PDAC with significantly higher accuracy compared with either biomarker individually.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-0235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102343PMC
May 2021

Utilisation of artificial intelligence for the development of an EUS-convolutional neural network model trained to enhance the diagnosis of autoimmune pancreatitis.

Gut 2021 Jul 7;70(7):1335-1344. Epub 2020 Oct 7.

Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA

Objective: The diagnosis of autoimmune pancreatitis (AIP) is challenging. Sonographic and cross-sectional imaging findings of AIP closely mimic pancreatic ductal adenocarcinoma (PDAC) and techniques for tissue sampling of AIP are suboptimal. These limitations often result in delayed or failed diagnosis, which negatively impact patient management and outcomes. This study aimed to create an endoscopic ultrasound (EUS)-based convolutional neural network (CNN) model trained to differentiate AIP from PDAC, chronic pancreatitis (CP) and normal pancreas (NP), with sufficient performance to analyse EUS video in real time.

Design: A database of still image and video data obtained from EUS examinations of cases of AIP, PDAC, CP and NP was used to develop a CNN. Occlusion heatmap analysis was used to identify sonographic features the CNN valued when differentiating AIP from PDAC.

Results: From 583 patients (146 AIP, 292 PDAC, 72 CP and 73 NP), a total of 1 174 461 unique EUS images were extracted. For video data, the CNN processed 955 EUS frames per second and was: 99% sensitive, 98% specific for distinguishing AIP from NP; 94% sensitive, 71% specific for distinguishing AIP from CP; 90% sensitive, 93% specific for distinguishing AIP from PDAC; and 90% sensitive, 85% specific for distinguishing AIP from all studied conditions (ie, PDAC, CP and NP).

Conclusion: The developed EUS-CNN model accurately differentiated AIP from PDAC and benign pancreatic conditions, thereby offering the capability of earlier and more accurate diagnosis. Use of this model offers the potential for more timely and appropriate patient care and improved outcome.
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http://dx.doi.org/10.1136/gutjnl-2020-322821DOI Listing
July 2021

Computerized tomography scan in pre-diagnostic pancreatic ductal adenocarcinoma: Stages of progression and potential benefits of early intervention: A retrospective study.

Pancreatology 2020 Oct 11;20(7):1495-1501. Epub 2020 Aug 11.

Division of Gastroenterology and Hepatology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address:

Background: The frequency, nature and timeline of changes on thin-slice (≤3 mm) multi-detector computerized tomography (CT) scans in the pre-diagnostic phase of pancreatic ductal adenocarcinoma (PDAC) are unknown. It is unclear if identifying imaging changes in this phase will improve PDAC survival beyond lead time.

Methods: From a cohort of 128 subjects (Cohort A) with CT scans done 3-36 months before diagnosis of PDAC we developed a CTgram defining CT Stages (CTS) I through IV in the radiological progression of pre-diagnostic PDAC. We constructed Cohort B of PDAC resected at CTS I and II and compared survival in CTS I and II in Cohort A (n = 22 each; control natural history cohort) vs Cohort B (n = 33 and 72, respectively; early interception cohort).

Results: CTs were abnormal in 16% and 85% at 24-36 and 3-6 months respectively, before PDAC diagnosis. The PDAC CTgram stages, findings and median lead times (months) to clinical diagnosis were: CTS I: Abrupt duct cut-off/duct dilatation (-12.8); CTS II: Low density mass confined to pancreas (-9.5), CTS III: Peri-pancreatic infiltration (-5.8), CTS IV: Distant metastases (only at diagnosis). PDAC survival was better in cohort B than in cohort A despite inclusion of lead time in Cohort A: CTS I (36 vs 17.2 months, p = 0.03), CTS II (35.2 vs 15.3 months, p = 0.04).

Conclusion: Starting 12-18 months before PDAC diagnosis, progressive and increasingly frequent changes occur on CT scans. Resection of PDAC at the time of pre-diagnostic CT changes is likely to provide survival benefit beyond lead time.
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http://dx.doi.org/10.1016/j.pan.2020.07.410DOI Listing
October 2020

Impact of disconnected pancreatic duct syndrome on endoscopic ultrasound-guided drainage of pancreatic fluid collections.

Endoscopy 2021 06 6;53(6):603-610. Epub 2020 Jul 6.

Division of Gastroenterology and Hepatology, Mayo Clinic at Rochester, Rochester, Minnesota, USA.

Background: Endoscopic intervention for pancreatic fluid collections (PFCs) with disconnected pancreatic duct syndrome (DPDS) has been associated with failures and increased need for additional endoscopic and non-endoscopic interventions. The primary aim of this study was to determine the outcomes of endoscopic ultrasound (EUS)-guided transmural drainage of PFCs in patients with DPDS.

Methods: In patients undergoing EUS-guided drainage of PFCs from January 2013 to January 2018, demographic profiles, procedural indications and details, adverse events, outcomes, and subsequent interventions were retrospectively collected. Overall treatment success was determined by PFC resolution on follow-up imaging or stent removal without recurrence.

Results: EUS-guided drainage of PFCs was performed in 141 patients. DPDS was present in 57 of them (40 %) and walled-off necrosis was the most frequent type of PFC (55 %). DPDS was not associated with lower clinical success, increased number of repeat interventions, or increased time to PFC resolution. Patients with DPDS were more likely to be treated with permanent transmural plastic double-pigtail stents (odds ratio [OR] 6.4; 95 % confidence interval [CI] 2.5 - 16.5;  < 0.001). However, when stents were removed, DPDS was associated with increased PFC recurrence after stent removal (OR 8.0; 95 %CI 1.2 - 381.8;  = 0.04).

Conclusions: DPDS frequently occurs in patients with PFCs but does not negatively impact successful resolution. DPDS is associated with increased PFC recurrence after stent removal.
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http://dx.doi.org/10.1055/a-1213-1489DOI Listing
June 2021

Pancreatic ductal adenocarcinoma is associated with a unique endocrinopathy distinct from type 2 diabetes mellitus.

Pancreatology 2020 Jul 22;20(5):929-935. Epub 2020 May 22.

Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine and Science, Rochester, MN, USA; Department of Medicine, Division of Endocrinology, Metabolism, Diabetes, and Nutrition, Mayo Clinic College of Medicine and Science, Rochester, MN, USA. Electronic address:

Introduction: The majority of patients with pancreatic ductal adenocarcinoma (PC) display either impaired fasting glucose/glucose intolerance or overt diabetes. However, the pathophysiologic basis of this association remains largely unexplained.

Methods: In this case-control study we aimed to study the morphological changes in the islets of patients with PC, compared to control patients with and without type 2 diabetes mellitus (T2DM). T2DM controls and PC cases had a lower β-cell area and average islet size and density compared to non-T2DM controls (p < 0.05).

Results: Compared to both T2DM and non-T2DM controls, mean α-cell area was significantly lower and β/α-ratio was higher in PC cases (p < 0.05). Furthermore, whereas islets in T2DM controls were characterized by disrupted islet architecture and presence of islet amyloid aggregates, islet composition in PC islets was not significantly different compared to non-T2DM controls (p > 0.05 vs. Control).

Conclusions: Our data shows that PC is associated with a unique pattern of islet pathology characterized by preserved architecture, absence of amyloid aggregates, and relative α-cell loss indicating that distinct mechanisms are likely involved in the pathophysiology of islet failure in PC-induced DM. Insights into the mechanisms mediating β-cell failure in PC can be important for our understanding of pathophysiology of PC.
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http://dx.doi.org/10.1016/j.pan.2020.05.010DOI Listing
July 2020

Molecular Diagnostics and Testing for Pancreatic Cysts.

Curr Treat Options Gastroenterol 2020 Jan 27. Epub 2020 Jan 27.

Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Sciences, 200 First St SW, Rochester, MN, 55905, USA.

Purpose Of Review: In current clinical practice, the diagnosis and management of pancreatic cystic lesions (PCLs) are based on guidelines that combine clinical and imaging findings. These guidelines usefully identify a large category of low-risk PCLs that do not require treatment. However, they have limited accuracy for diagnosis of advanced neoplasia in worrisome and high-risk PCLs. Novel molecular markers that can accurately detect advanced neoplasia in PCLs can transform the care of patients with PCLs. We reviewed the recent medical literature on molecular diagnostics of PCLs and summarized molecular biomarkers assayed in cyst fluid, pancreatic juice, and blood.

Recent Findings: Several studies have been recently published describing promising early results in genetic, epigenetic, and protein biomarkers from cyst fluid to help in both histologic diagnosis and detection of advanced neoplasia. The majority of studies have been completed using opportunistically collected archival cyst fluid and few report validation in independent sample sets. Results of ongoing multicenter prospective validation studies are awaited and will help define the best combination of cyst fluid molecular markers. In multifocal PCLs communicating with the pancreatic ductal system, a pancreatic juice biomarker is likely to be less invasive and more informative. Novel biomarkers in pancreatic juice and blood are in early phases of study. The field of molecular diagnostic biomarkers for PCLs is rapidly evolving with several promising candidate markers being prospectively evaluated. In the near future, these novel molecular markers, combined with advances in imaging technology, will transform clinical decision-making in the management of PCLs and improve patient outcomes.
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http://dx.doi.org/10.1007/s11938-020-00270-6DOI Listing
January 2020

Significance of peripheral eosinophilia for diagnosis of IgG4-related disease in subjects with elevated serum IgG4 levels.

Pancreatology 2020 Jan 27;20(1):74-78. Epub 2019 Nov 27.

Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, USA. Electronic address:

Objectives: In this study, we aim to assess the diagnostic utility of elevated serum IgG4 (sIgG4) concentration alone and in combination with peripheral eosinophilia (PE) for IgG4-related disease (IgG4-RD).

Methods: From the Mayo Clinic, Rochester electronic medical record database we identified 409 patients with above normal levels of sIgG4 (reference range 121-140 mg/dL) who had sIgG4 measured to differentiate IgG4-RD from another disease.

Results: Among 409 patients with any elevation in sIgG4 levels, 129 (31.5%) had a definite diagnosis of IgG4-RD. The prevalence of PE increased with increasing sIgG4 levels and was more likely to be seen in subjects with IgG4-RD vs. non-IgG4-RD at ≥1X (n = 35/120, 29.2% vs. n = 23/258, 8.9%; p < 0.001), ≥2X (n = 23/64, 35.9% vs. n = 5/54,9.3%; p = 0.001) and ≥3X (n = 18/42, 42.9% vs. n = 0/9, 0%; p = 0.015) of sIgG4 upper limit of normal (ULN), respectively. After adjusting for gender and age, sIgG4 levels ≥ 2X ULN with PE as a predictor, had a higher positive predictive value in predicting IgG4-RD (72.2% vs. 65.9%) with an Area Under the Receiver Operatic Characteristic Curve (AUC) of 0.776, compared to sIgG4 ≥ 2X ULN without PE predictor (AUC = 0.74), p = 0.016. PE, sIgG4≥2X ULN, male gender, and age independently predicted the disease with odds ratio of 4.89 (95% CI:2.51-9.54), 3.78 (95% CI:2.27-6.28), 2.78 (95% CI:1.55-4.97), and 1.03 (95% CI:1.02-1.05), respectively.

Conclusion: Even in subjects in whom IgG4-RD is suspected, only a minority (∼30%) with elevated sIgG4 levels have IgG4-RD. sIgG4 by itself is more specific at higher levels, though never diagnostic. PE increases with increasing sIgG4 and adds diagnostic value at higher sIgG4 levels.
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http://dx.doi.org/10.1016/j.pan.2019.11.016DOI Listing
January 2020

Why are we performing fewer cholecystectomies for mild acute biliary pancreatitis? Trends and predictors of cholecystectomy from the National Readmissions Database (2010-2014).

Gastroenterol Rep (Oxf) 2019 Oct 29;7(5):331-337. Epub 2019 Aug 29.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.

Background: Current guidelines recommend cholecystectomy for patients with mild acute biliary pancreatitis (MABP) during the index admission because it is associated with better outcomes. In this study, we aimed to assess national trends in cholecystectomy during index admissions for MABP and to identify factors associated with cholecystectomy completion and 30-day readmission.

Methods: Using diagnostic codes and the National Readmissions Database, we identified patients admitted with MABP between 2010 and 2014. Differences in cholecystectomy rates were computed on the basis of various characteristics. We conducted a multivariable analysis to identify factors associated with 30-day readmission and cholecystectomy during the same admission.

Results: We identified 255,695 unique index MABP cases (41.3% male) and the 30-day readmission rate was 12.6%. Overall, 43.8% underwent cholecystectomy and 25% underwent endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy. We observed a decreasing trend in both procedures during the study period ( < 0.001). In multivariate analysis, odds of 30-day readmission were reduced for patients undergoing ERCP with sphincterotomy (odds ratio, 0.78; 95% confidence interval, 0.74-0.84) or cholecystectomy (odds ratio, 0.37; 95% confidence interval, 0.35-0.39).

Conclusions: For patients with MABP, cholecystectomy or ERCP with sphincterotomy during the index admission decreased the risk of 30-day readmission. Despite this benefit and national guidelines recommending cholecystectomy during the index MABP admission, the rate of cholecystectomies performed nationally decreased during the study period. Further research is needed to understand the implications and reasons underlying this deviation from guidelines.
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http://dx.doi.org/10.1093/gastro/goz037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821273PMC
October 2019

Peripheral blood monocyte counts are elevated in the pre-diagnostic phase of pancreatic cancer: A population based study.

Pancreatology 2019 Dec 10;19(8):1043-1048. Epub 2019 Oct 10.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA. Electronic address:

Background: Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) is associated with improved outcomes. A biomarker with incremental change in the pre-diagnostic phase of the disease would be valuable for early detection. In our clinical experience, we have observed elevated peripheral blood monocyte (PBM) counts in PDAC patients at diagnosis. In this study, we aimed to compare PBM counts in PDAC cases and healthy controls at diagnosis and in the 2-year pre-diagnostic period.

Methods: Using the Rochester Epidemiology Project database, we identified all patients diagnosed with PDAC between 2000 and 2015 (n = 219) and age-and gender-matched disease-free controls (n = 438). PBM counts and temporal trends were analyzed over a 24 month period before PDAC diagnosis. The groups were compared using Fisher's exact test and t-test.

Results: At diagnosis, compared to controls PDAC cases more often had monocytosis (23% vs 8%; p < 0.001) and higher mean PBM count (x10/L) (0.73 vs 0.59; p < 0.001). In the 2-year pre-diagnostic period, mean PBM counts were significantly higher in PDAC cases in the interval from 6 months to diagnosis (0.69 vs 0.61; p = 0.03). PDAC cases with monocytosis at diagnosis had a significantly lower median survival (1.9 months vs. 7.6 months; p = 0.001).

Conclusion: Monocytosis is more prevalent in PDAC patients at diagnosis compared to controls and is associated with lower median survival. In a subset of patients, PBM count elevation precedes PDAC diagnosis by 6 months. This novel observation can possibly augment strategies for early diagnosis of PDAC but needs further study.
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http://dx.doi.org/10.1016/j.pan.2019.10.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897401PMC
December 2019

Methylated DNA in Pancreatic Juice Distinguishes Patients With Pancreatic Cancer From Controls.

Clin Gastroenterol Hepatol 2020 03 16;18(3):676-683.e3. Epub 2019 Jul 16.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.

Background & Aims: Precursors of pancreatic cancer arise in the ductal epithelium; markers exfoliated into pancreatic juice might be used to detect high-grade dysplasia (HGD) and cancer. Specific methylated DNA sequences in pancreatic tissue have been associated with adenocarcinoma. We analyzed these methylated DNA markers (MDMs) in pancreatic juice samples from patients with pancreatic ductal adenocarcinomas (PDACs) or intraductal papillary mucinous neoplasms (IPMNs) with HGD (cases), and assessed their ability to discriminate these patients from individuals without dysplasia or with IPMNs with low-grade dysplasia (controls).

Methods: We obtained pancreatic juice samples from 38 patients (35 with biopsy-proven PDAC or pancreatic cystic lesions with invasive cancer and 3 with HGD) and 73 controls (32 with normal pancreas and 41 with benign disease), collected endoscopically from the duodenum after secretin administration from February 2015 through November 2016 at 3 medical centers. Samples were analyzed for the presence of 14 MDMs (in the genes NDRG4, BMP3, TBX15, C13orf18, PRKCB, CLEC11A, CD1D, ELMO1, IGF2BP1, RYR2, ADCY1, FER1L4, EMX1, and LRRC4), by quantitative allele-specific real-time target and signal amplification. We performed area under the receiver operating characteristic curve analyses to determine the ability of each marker, and panels of markers, to distinguish patients with HGD and cancer from controls. MDMs were combined to form a panel for detection using recursive partition trees.

Results: We identified a group of 3 MDMs (at C13orf18, FER1L4, and BMP3) in pancreatic juice that distinguished cases from controls with an area under the receiver operating characteristic value of 0.90 (95% CI, 0.83-0.97). Using a specificity cut-off value of 86%, this group of MDMs distinguished patients with any stage of pancreatic cancer from controls with 83% sensitivity (95% CI, 66%-93%) and identified patients with stage I or II PDAC or IPMN with HGD with 80% sensitivity (95% CI, 56%-95%).

Conclusions: We identified a group of 3 MDMs in pancreatic juice that identify patients with pancreatic cancer with an area under the receiver operating characteristic value of 0.90, including patients with early stage disease or advanced precancer. These DNA methylation patterns might be included in algorithms for early detection of pancreatic cancer, especially in high-risk cohorts. Further optimization and clinical studies are needed.
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http://dx.doi.org/10.1016/j.cgh.2019.07.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6984349PMC
March 2020

Novel Methylated DNA Markers Discriminate Advanced Neoplasia in Pancreatic Cysts: Marker Discovery, Tissue Validation, and Cyst Fluid Testing.

Am J Gastroenterol 2019 09;114(9):1539-1549

Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, Minnesota, USA.

Objectives: Pancreatic cystic lesions (PCLs) may be precancerous. Those likely to harbor high-grade dysplasia (HGD) or pancreatic cancer (PC) are targets for surgical resection. Current algorithms to predict advanced neoplasia (HGD/PC) in PCLs lack diagnostic accuracy. In pancreatic tissue and cyst fluid (CF) from PCLs, we sought to identify and validate novel methylated DNA markers (MDMs) that discriminate HGD/PC from low-grade dysplasia (LGD) or no dysplasia (ND).

Methods: From an unbiased whole-methylome discovery approach using predefined selection criteria followed by multistep validation on case (HGD or PC) and control (ND or LGD) tissues, we identified discriminant MDMs. Top candidate MDMs were then assayed by quantitative methylation-specific polymerase chain reaction on archival CF from surgically resected PCLs.

Results: Of 25 discriminant MDMs identified in tissue, 13 were selected for validation in 134 CF samples (21 cases [8 HGD, 13 PC], 113 controls [45 ND, 68 LGD]). A tree-based algorithm using 2 CF-MDMs (TBX15, BMP3) achieved sensitivity and specificity above 90%. Discrimination was significantly better by this CF-MDM panel than by mutant KRAS or carcinoembryonic antigen, with areas under the receiver operating characteristic curve of 0.93 (95% confidence interval: 0.86-0.99), 0.71 (0.57-0.85), and 0.72 (0.60-0.84), respectively. Cutoffs for the MDM panel applied to an independent CF validation set (31 cases, 56 controls) yielded similarly high discrimination, areas under the receiver operating characteristic curve = 0.86 (95% confidence interval: 0.77-0.94, P = 0.2).

Discussion: Novel MDMs discovered and validated in tissue accurately identify PCLs harboring HGD/PC. A panel of 2 MDMs assayed in CF yielded results with potential to enhance current risk prediction algorithms. Prospective studies are indicated to optimize and further evaluate CF-MDMs for clinical use.
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http://dx.doi.org/10.14309/ajg.0000000000000284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294458PMC
September 2019

Clinical spectrum of adult patients with annular pancreas: Findings from a large single institution cohort.

Pancreatology 2019 Mar 3;19(2):290-295. Epub 2019 Jan 3.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA. Electronic address:

Background And Aims: Annular pancreas (AnnP) is a rare congenital abnormality that results from the presence of a complete or partial ring of pancreatic tissue surrounding the descending portion of the duodenum. While the clinical presentation and management of AnnP in neonates and infants has been well described, the complete spectrum of clinical presentation of AP in adults is not very clear. We aimed to describe the clinical spectrum of presentation and management of adult patients with AnnP.

Methods: Using the electronic medical record, we identified 198 patients with radiologically and/or surgically confirmed AnnP evaluated at Mayo Clinic between 1995 and 2017.

Results: The mean age of the study population at diagnosis was 55.1 (±18.3) years (60% female). 60% of patients did not have symptoms attributable to pancreatic disease at the time of diagnosis and were diagnosed incidentally. Computed tomography (CT) was the most common modality (64%) of diagnosis. Among symptomatic patients, abdominal pain (50%), duodenal obstruction (31%) and acute pancreatitis (16%) were the most common symptoms (non-exclusive). While most patients with duodenal obstruction required surgery, all patients with acute pancreatitis could be managed conservatively in the absence of competing indications for intervention.

Conclusion: AnnP may remain asymptomatic well into adulthood and be incidentally detected on abdominal imaging done for other indications. While surgery remains the mainstay of treatment in patients presenting with duodenal obstruction, a majority of these adult symptomatic patients with AnnP, including those with acute pancreatitis require no further treatment.
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http://dx.doi.org/10.1016/j.pan.2018.12.009DOI Listing
March 2019

A Set Up for Small Intestinal Bacterial Overgrowth.

Gastroenterology 2019 06 11;156(8):e5-e6. Epub 2019 Jan 11.

Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota; Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.

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http://dx.doi.org/10.1053/j.gastro.2019.01.005DOI Listing
June 2019

High-Grade Dysplasia in Resected Main-Duct Intraductal Papillary Mucinous Neoplasm (MD-IPMN) is Associated with an Increased Risk of Subsequent Pancreatic Cancer.

Am J Gastroenterol 2019 03;114(3):524-529

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.

Background: There is lack of consensus on post-operative surveillance for resected non-invasive intraductal papillary neoplasms (IPMNs). In this study we explored risk factors for subsequent PC in patients with MD-IPMN undergoing partial pancreatectomy.

Methods: We searched the Mayo Clinic surgical pathology database for all cases of resected MD-IPMN between 1997 and 2014. Cases with histologically confirmed main pancreatic duct involvement either isolated or in a mixed pattern with branch-duct involvement were included. Outcomes of PC in the remnant pancreas, and death related to MD-IPMN were assessed with survival analyses (Kaplan-Meier and Cox regression).

Results: Among the 179 patients with resected MD-IPMN the incidence of concomitant PC and high-grade dysplasia (HGD) in the resected specimen was 23 and 14%, respectively. The mean duration of follow-up was 4.31 years (range 0.12-13.5 years). Excluding 28 subjects who either underwent initial total pancreatectomy or partial pancreatectomy with surgical margins positive for PC/HGD, the 5-year incidence of subsequent PC was 12%, including 60.6% and 15.6% in those with initial PC and HGD, respectively. The 10-year incidence of PC was 21.2% overall, 60.6% for PC, 38.3% for HGD, and 3.0% for LGD. Risk of subsequent PC was significantly higher for those with initial PC compared with HGD (HR = 4.95, 95% CI: 1.63-15.03, p = 0.005 and for HGD compared with LGD (HR = 11.30, 95% CI: 1.55-82.26, p = 0.017).

Conclusions: Patients with MD-IPMN with PC or HGD undergoing segmental pancreatectomy are at higher risk of subsequent PC and may benefit from post-operative surveillance. The post-operative surveillance intervals in resected MD-IPMNs need to be tailored based on dysplasia grade.
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http://dx.doi.org/10.1038/s41395-018-0403-2DOI Listing
March 2019

Role of Diagnostic Preoperative Upper Gastrointestinal Endoscopy in Radiologically Confirmed Gastric Volvulus.

Dig Dis Sci 2018 11 19;63(11):3091-3096. Epub 2018 Jul 19.

Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.

Background And Aims: Gastric volvulus (GV) is a life-threatening condition that warrants prompt diagnosis and treatment. GV is a radiologic diagnosis. The role of preoperative upper gastrointestinal endoscopy (UGIE) for individuals with radiologically confirmed GV is poorly defined. Our objective was to assess the diagnostic yield of UGIE in the preoperative evaluation of patients presenting with radiologically confirmed GV.

Methods: Retrospective review of all adult patients undergoing surgery for GV between July 1996 and August 2016 has been carried out. We performed analyses evaluating diagnostic yield of preoperative UGIE and compared outcomes in patients who did and did not undergo preoperative UGIE. Outcomes were diagnostic yield of preoperative UGIE, length of hospital stay, postoperative complications, and mortality at 30 days and 1 year.

Results: In the preoperative UGIE group, the diagnostic yield was 34.6% (27/78). The most common endoscopic findings were erosive esophagitis (13/27) and clean based gastric or duodenal ulcers (5/27). There were no cases of esophago-gastric malignancy. Three patients had ulcers with stigmata of recent bleeding, and three patients had features suggestive of gastric ischemia. Endoscopic findings did not influence surgical management. There was no statistically significant difference in mortality between patients who did and did not undergo preoperative UGIE, both at 30 days (0 vs. 2.5%) and 1 year (3.8 vs. 7.5%).

Conclusion: Among patients with radiologically confirmed GV, preoperative UGIE rarely demonstrates clinically significant findings and can potentially delay definitive surgical intervention.
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http://dx.doi.org/10.1007/s10620-018-5210-5DOI Listing
November 2018

A Tale of Three Tails and a Cystic Lesion: A Rare Cause of Recurrent Acute Pancreatitis.

Am J Gastroenterol 2018 Sep 2;113(9):1398-1399. Epub 2018 Jul 2.

Division of Gastroenterology, Mayo Clinic, Rochester, MN 55905, USA. Division of Diagnostic Radiology, Mayo Clinic, Rochester, MN 55905, USA. Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN 55905, USA. Division of Anatomic Pathology, Mayo Clinic, Rochester, MN 55905, USA.

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http://dx.doi.org/10.1038/s41395-018-0178-5DOI Listing
September 2018

Rituximab Maintenance Therapy Reduces Rate of Relapse of Pancreaticobiliary Immunoglobulin G4-related Disease.

Clin Gastroenterol Hepatol 2018 12 8;16(12):1947-1953. Epub 2018 Mar 8.

Division of Hematology and Oncology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.

Background & Aims: IgG4-related disease (IgG4-RD), a multi-organ fibroinflammatory syndrome, typically responds to steroids. However, some cases are steroid resistant, and pancreaticobiliary IgG4-RD commonly relapses after steroid withdrawal. Rituximab induces remission of IgG4-RD, but the need for and safety of maintenance rituximab treatment are unknown. We compared outcomes of patients with pancreaticobiliary IgG4-RD treated with or without maintenance rituximab therapy.

Methods: We performed a retrospective study of patients with pancreaticobiliary IgG4-RD treated with rituximab at the Mayo Clinic in Rochester, Minnesota, from January 2005 through December 2015. The cohort was divided into patients who received only rituximab induction therapy (group 1, n = 14) and patients who received rituximab induction followed by maintenance therapy (group 2, n = 29). We collected data on recurrence of IgG4-RD symptoms and findings, as well as information on evaluations, treatment, and adverse events.

Results: Median follow-up times were similar between group 1 (34 mo) and group 2 (27 mo) (P = .99). Thirty-seven patients (86%) were in steroid-free remission 6 months after rituximab initiation. A higher proportion of patients in group 1 had disease relapse (3-year event rate, 45%) than in group 2 (3-year event rate, 11%) (P = .034). Younger age, higher IgG4 responder index score after induction therapy, and increased serum levels of alkaline phosphatase at baseline or after rituximab induction were associated with relapse. Infections developed in 6 of 43 patients, all in group 2 (P = .067 vs group 1); all but 1 occurred during maintenance therapy.

Conclusions: In a retrospective study of patients with pancreaticobiliary IgG4-RD, we found rituximab maintenance therapy prolongs remission. Relapses are uncommon among patients receiving maintenance therapy, but maintenance therapy may increase risk of infection. Patients with factors that predict relapse could be candidates for rituximab maintenance therapy.
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http://dx.doi.org/10.1016/j.cgh.2018.02.049DOI Listing
December 2018

Fatty Pancreas: Should We Be Concerned?

Pancreas 2017 Nov/Dec;46(10):1251-1258

From the *Division of Gastroenterology and Hepatology, †Department of Radiology, Mayo Clinic, Rochester, MN; and ‡Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, AZ.

The metabolic consequences of visceral fat deposition are well known, and the presence of intrapancreatic fat (IPF) has been recognized for decades. However, our knowledge about the distribution of fat in the pancreas and its clinical implications is in a nascent stage. Various terms have been proposed to describe IPF; for the purpose of this narrative review, we chose the general term fatty pancreas. Herein, we describe the radiologic, endoscopic, and histopathologic aspects of diagnosing fatty pancreas and provide an overview of the diseases associated with this condition. Our purpose is to highlight diagnostic challenges and identify specific clinical questions that would benefit from further study. As evident in this review, IPF is associated with various metabolic diseases, pancreatitis, pancreatic cancer, and precancer-yet establishing causality needs careful, further study.
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http://dx.doi.org/10.1097/MPA.0000000000000941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6689238PMC
June 2018

EUS-guided pancreatic pseudoaneurysm therapy: better to be lucky than good.

Gastrointest Endosc 2018 Apr 10;87(4):1155-1156. Epub 2017 Oct 10.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.

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http://dx.doi.org/10.1016/j.gie.2017.09.043DOI Listing
April 2018

Carbon Dioxide Insufflation During Endoscopic Pancreatic Function Tests Does Not Alter Duodenal Aspirate Bicarbonate Concentrations.

Pancreas 2017 08;46(7):e62-e63

Department of Internal Medicine, Saint Peter's University Hospital-Rutgers, Robert Wood Johnson School of Medicine, New Brunswick, NJDivision of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN

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http://dx.doi.org/10.1097/MPA.0000000000000857DOI Listing
August 2017

Reply to "Pancreatic Volume in Diabetes Mellitus".

Pancreas 2017 07;46(6):e51-e52

Department of Internal Medicine, Rutgers Robert Wood Johnson Saint Peters University Hospital New Brunswick, NJ Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN

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http://dx.doi.org/10.1097/MPA.0000000000000824DOI Listing
July 2017

A Young Man With Abdominal Pain, Weight Loss, and Jaundice.

Gastroenterology 2017 Jun 4;152(8):1836-1838. Epub 2017 May 4.

Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.

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http://dx.doi.org/10.1053/j.gastro.2016.12.044DOI Listing
June 2017

Large-caliber metal stents versus plastic stents for the management of pancreatic walled-off necrosis.

Gastrointest Endosc 2018 Jan 3;87(1):141-149. Epub 2017 May 3.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.

Background And Aims: Symptomatic pancreatic walled-off necrosis (WON) may be managed by endoscopic transmural drainage and endoscopic transmural necrosectomy, with stent placement at endoscopic drainage sites. The optimal stent choice is yet to be determined. We compared outcomes after endoscopic management of WON using either large-caliber fully covered self-expandable metal stents (LC-SEMSs) or double-pigtail plastic stents (DPPSs).

Methods: We performed a retrospective comparison of outcomes among patients who received LC-SEMSs or DPPSs before endoscopic transmural necrosectomy for WON.

Results: Among 94 patients included, WON resolution rates did not differ between the DPPS (36 patients) and LC-SEMS (58 patients) groups, whether concomitant percutaneous drainage was considered a failure (75% vs 82.8%; P = .36) or not (91.7% vs 94.8%; P = .55). Of 75 patients (80%) successfully treated without percutaneous drainage, 37 (49%) underwent endoscopic transmural drainage without subsequent endoscopic transmural necrosectomy. WON was more likely to resolve without subsequent endoscopic transmural necrosectomy in the LC-SEMS group than the DPPS group (60.4% vs 30.8%; P = .01). WON resolution without subsequent endoscopic transmural necrosectomy remained more likely with LC-SEMSs (odds ratio, 4.5 [95% confidence interval, 1.5-15.5]) after adjusting for patient age and size and location of WON. Rates of adverse events were similar except for clinically significant bleeding requiring endoscopic intervention, which was higher with DPPSs than LC-SEMSs (14% vs 2%; P = .02).

Conclusion: Management of pancreatic WON with LC-SEMSs appears to decrease both the need for repeated necrosectomy procedures and the risk of intervention-related hemorrhage.
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http://dx.doi.org/10.1016/j.gie.2017.04.032DOI Listing
January 2018
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