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Background/objectives: Total pancreatectomy with islet autotransplantation (TPIAT) is considered for managing chronic pancreatitis in selected patients when medical and endoscopic interventions have not provided adequate relief from debilitating pain. Although more centers are performing TPIAT, we lack large, multi-center studies to guide decisions about selecting candidates for and timing of TPIAT., Methods: Multiple centers across the United States (9 to date) performing TPIAT are prospectively enrolling patients undergoing TPIAT for chronic pancreatitis into the Prospective Observational Study of TPIAT (POST), a NIDDK funded study with a goal of accruing 450 TPIAT recipients. Baseline data include participant phenotype, pancreatitis history, and medical/psychological comorbidities from medical records, participant interview, and participant self-report (Medical Outcomes Survey Short Form-12, EQ-5D, andPROMIS inventories for pain interference, depression, and anxiety). Outcome measures are collected to at least 1 year after TPIAT, including the same participant questionnaires, visual analog pain scale, pain interference scores, opioid requirements, insulin requirements, islet graft function, and hemoglobin A1c. Health resource utilization data are collected for a cost-effectiveness analysis. Biorepository specimens including urine, serum/plasma, genetic material (saliva and blood), and pancreas tissue are collected for future study., Conclusions: This ongoing multicenter research study will enroll and follow TPIAT recipients, aiming to evaluate patient selection and timing for TPIAT to optimize pain relief, quality of life, and diabetes outcomes, and to measure the procedure's cost-effectiveness. A biorepository is also established for future ancillary studies., (Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

The goal of nutritional support in acute pancreatitis is to reduce inflammation, prevent nutritional depletion, correct a negative nitrogen balance, and improve outcomes. Enteral nutrition (EN) in severe acute pancreatitis (SAP) should be preferred to parenteral nutrition. It maintains the integrity of the gut barrier, decreases intestinal permeability, downregulates the systemic inflammatory response, maintains intestinal microbiota equilibrium, and reduces the complications of the early phase of SAP, improving morbidity and possibly improving mortality, and it is less expensive. Further studies to understand optimal timing of nutrition, route of delivery of EN, and the type of nutrition and nutrients are necessary., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background and Aims: Direct pancreas juice testing of bicarbonate, lipase, or trypsin after stimulation by secretin or cholecystokinin is used to determine exocrine function, a surrogate for diagnosing chronic pancreatitis (CP). Endoscopic pancreas function tests (ePFTs), where a peak bicarbonate concentration (PBC) ≥80 mEq/L in pancreas juice is considered normal, are now used more frequently. In this ePFT, aspirates start 35 minutes after secretin administration because pancreas output peaks 30 minutes after secretagogue administration. The performance of ePFT in a cohort of patients with a presumptive diagnosis of CP referred to a pancreas clinic for consideration of an intervention including total pancreatectomy and islet autotransplantation was studied, compared with EUS, ERCP, histology, and consensus diagnosis. The effect of sedation, narcotic use, aspirate volume, body mass index, age, and proton pump inhibitors (PPIs) on test performance is reported., Methods: After a test dose, synthetic human secretin was administered intravenously, and 30 minutes later sedation was achieved with midazolam and fentanyl or propofol. A gastroscope was advanced to the major papilla where 4 continuous aspiration samples were performed at 5-minute intervals in sealed bottles. PBC ≥80 mEq/L was normal., Results: Eighty-one patients had ePFTs from August 2010 through October 2015. Twenty-seven patients (33%) were diagnosed with CP. Eighteen of the 27 patients with CP and 1 of the 54 patients without CP had an abnormal ePFT, producing a sensitivity of 66% (95% CI, 46.0-83.5), specificity 98% (95% CI, 90.1-99.9), positive predictive value 94.7% (95% CI, 74-99.9), and negative predictive value 85.5% (95% CI, 74.2-93.1). ERCP and PBC concordance was generally poor, but none of the patients without CP had major EUS changes, and only 3 patients with a PBC <80 mEq/L had a normal EUS. The PBC was affected by narcotics and PPI use., Conclusion: A 20-minute ePFT after secretin administration had a marginal sensitivity for diagnosis of CP. The diagnosis of CP should not rely on a single study and certainly not a PFT. The duodenal aspirate volume did not correlate with the PBC, which contrasts with current secretin-enhanced MRCP knowledge; therefore, further studies on this subject are warranted. Neither type of sedation, BMI, nor age affected test performance. Narcotics and PPIs may affect the PBC, so borderline results should be interpreted with caution in these groups., (Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Total pancreatectomy (TP) with islet autotransplantation (IAT) is a highly selected treatment for severe pain associated with chronic pancreatitis (CP) after exhausting medical and endoscopic therapies. The effect of duration of CP on TP-IAT has not been clarified., Methods: Retrospective review of a consecutive cohort undergoing TP-IAT was performed. Patients were classified according to islet dose of <2500 IEQ/kg, 2500 to 5000 IEQ/kg, and >5000 IEQ/kg. Islet yield and metabolic outcomes were compared to disease duration of CP., Results: A total of 76 CP patients underwent TP-IAT. Longer disease duration was associated with lower islet yield transplanted (Spearman's correlation = -0.24; p = 0.04) for total cohort. Highest absolute value of the coefficient was found in patients with hereditary CP when study subjects were classified by the etiology of CP (correlation = -0.72; p = 0.02). Higher islet yields were significantly associated with better metabolic outcomes (7.6 ± 1.1 vs 6.6 ± 1.1% of HbA1c post-TPIAT in patients with <2500 and >5000 IEQ/kg transplanted, respectively; p = 0.04)., Conclusions: The duration of CP could affect islet yield and metabolic outcomes. The time since the diagnosis of CP should be considered when selecting patients for islet autotransplantation.

Objective: In patients with acute upper gastrointestinal hemorrhage, standard practice is to transfuse packed red blood cells, often to an arbitrary level of hemoglobin or hematocrit (typically 10 g/dL and 30%, respectively) before endoscopy. Therefore, we aimed to determine first whether performing endoscopy in patients with upper gastrointestinal hemorrhage and a low hematocrit is safe and whether it predicts outcomes., Methods: This cohort study included patients with carefully defined upper gastrointestinal hemorrhage captured in our gastrointestinal Healthcare Registry who underwent esophagogastroduodenoscopy. Patients were placed into 2 groups: low hematocrit (<30%) or high hematocrit (>30%). Clinical variables and outcomes, including cardiovascular events, intensive care unit transfer, and death, were measured., Results: A total of 920 patients meeting entry criteria were identified. Baseline features among those with a low and high hematocrit were identical. Eight cardiovascular events occurred during or after esophagogastroduodenoscopy, including 5 of 587 (1%) in the less than 30% hematocrit group and 3 of 333 (1%) in the greater than 30% hematocrit group (P=.29). Blood transfusions were more common in the low hematocrit group (74% vs 24%, P<.001). However, correlation between the amount of blood transfused and hematocrit level was poor, and the number units of blood transfused was highly variable. There was no significant mortality difference in the 2 hematocrit groups., Conclusion: Most patients with upper gastrointestinal hemorrhage presented with a hematocrit less than 30%. Performing endoscopy in patients with a low hematocrit was clearly safe; these data strongly imply that waiting for the hematocrit to reach a certain level before endoscopy is not necessary., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The effectiveness of pancreatic islet isolation must be maximized to make islet cell transplantation (ICT) a standard therapy. We have performed 100 human islet isolations at Baylor Research Institute including islet isolations for research, for clinical allogeneic transplantation, and for autologous islet transplantation. In this study, we analyzed the results of these isolations. First, we assessed 79 islet isolations using brain-dead donors to determine variables associated with successful islet isolation. Univariate logistic regression analysis revealed that seven variables influenced the success of islet isolation for allogeneic ICT: cause of death, mechanism of death, techniques for pancreas procurement and preservation, heavy fatty infiltration, collagenase type, dilution time, and islet purification method. Multivariate regression analysis revealed that only the current isolation protocol, the Baylor Islet Isolation Method (BIIM)-with its four required elements of pancreas procurement by the team, pancreatic ductal injection, the two-layer method with perfluorocarbon, and density-adjusted density gradient purification-had a significant positive impact on successful islet isolation (P = 0.02). Second, we compared allogeneic and autologous ICT using the BIIM. There were no significant differences in islet yields between allogeneic and autologous ICT using the BIIM; total islet yield after purification was 628 ± 84 × 10(3) IE in allogeneic ICT vs. 576 ± 49 × 10(3) IE in autologous ICT (P = 0.59). This retrospective study revealed that the BIIM provided favorable outcomes for both autologous and allogeneic ICT.

The goal of total pancreatectomy followed by autologous islet cell transplantation is to manage pain and prevent surgical diabetes for patients with severe chronic pancreatitis. We performed this procedure in 17 patients from November 2006 to October 2009 at Baylor University Medical Center. All patients were included in this retrospective study and were divided into two groups based on islet yield in the final product based on patient body weight: a low-yield group (<5000 IE/kg) and a high-yield group (>/=5000 IE/kg). There were significant differences between the two groups in the rate of pancreatic findings on computed tomography (low vs high group, 88% vs 22%: P = 0.02), Cambridge classification score for endoscopic retrograde cholangiopancreatography (3.8 +/- 0.2 vs 2.1 +/- 0.6: P = 0.03), number of positive endoscopic ultrasonography criteria (6.0 +/- 0.8 vs 3.5 +/- 0.4: P = 0.04), and distension score (1.9 +/- 0.4 vs 3.7 +/- 0.2: P = 0.006). A significant reduction in narcotics use after the operation was observed in both groups (P = 0.03 and P = 0.009 in the low and high groups, respectively, using a paired t test). Excellent graft function and glycemic control after the transplantation were also demonstrated in both groups. Patients in the high-yield group were in the early stage of chronic pancreatitis, which led to excellent pancreatic distention for islet isolation; however, the excellent clinical outcomes were observed in both low- and high-yield groups.

Overtube-assisted enteroscopy has expanded therapeutic options for the small bowel, but the effectiveness of spiral tip overtube-assisted endoscopy for retrograde small bowel evaluation is not known. This retrospective study reviewed the results of retrograde enteroscopy procedures among six consecutive patients. In these patients, cecal retroflexion was necessary to enter the terminal ileum when using an enteroscope, and 40 to 130 cm of the distal small bowel was intubated. The average procedure time was 52 minutes. The procedure was diagnostic in four patients, and successful endoscopic therapy was performed in three patients, including completion of a polypectomy at the ileocecal valve, resolution of a distal intestinal obstruction in a patient with cystic fibrosis, and a small bowel anastomotic stricture release. There were no procedure-related complications. Overtube-assisted enteroscopy with the spiral tip overtube allows for antegrade or retrograde evaluation of the small bowel. Pan-enteroscopy may become possible as the technique and equipment improve. The advantages of the different forms of overtube-assisted enteroscopy (spiral, single, and double balloon) need to be determined.

Context: The main objective of pancreatic cyst fluid analysis is to differentiate mucin-producing or malignant cysts from other cysts which have a benign course. K-ras-2 point mutation and at least two mutations of allelic imbalance or loss of heterozygosity with good quality DNA has been suggested to predict mucinous cystic neoplasm (MCN). Elevated carcinogenic embryonic antigen (CEA) level in cyst fluid has also been shown to be predictive of mucinous or malignant cysts., Objective: Identify the clinical impact of DNA mutational analysis of pancreatic cyst fluid with its correlation to cyst fluid chemistry and histologic analysis., Patients: This retrospective analysis included all consecutive patients with pancreatic cysts who presented for evaluation by endoscopic ultrasound (EUS) with fine needle aspiration (FNA) over an 18 month period until November 2007., Main Outcome Measures: DNA analysis performed by Pathfinder TG (RedPath Integrated Pathology, Inc., Pittsburgh, PA, USA) and fluid CEA exceeding 192 ng/dL were used to suggest mucinous or malignant cysts. These parameters were compared to surgical histology or cytopathology of FNA specimens., Results: Twenty-seven consecutive patients with cysts had samples submitted for DNA analysis which included 15 men and 12 women (mean age 62.8 and 61.3 years, respectively). In 20 patients, all parameters including cyst fluid, DNA analysis, and histology were available for comparison. Consistent findings were seen in 7/20 (35%) in which all parameters suggested negative benign findings. CEA level was elevated in 7 patients of which 4 had mucinous or malignant histology. In the remaining 13 patients with low CEA levels, 11 had negative histology. The sensitivity and specificity of CEA based on these results was 66% and 78.6% respectively. The positive predictive value (PPV) of CEA was 57% and the negative predictive value (NPV) was 84.6%. K-ras-2 mutation was detected in 3 patients, absent in 17 patients and falsely negative in 4 cases based on histology. The sensitivity and specificity were 33% and 92.6% respectively. The PPV was 66% and NPV was 76%. Detection of loss of heterozygosity mutations was noted in 7 patients, of which 4 were falsely positive. In the remaining 13 patients, 3 were falsely negative. The sensitivity and specificity were 50% and 71% respectively. The PPV was 42.9% and NPV was 76.9%. In a group of 6 patients with available surgical histology demonstrating mucin-producing or malignant cysts, fluid CEA level had a sensitivity of 66.7%. However, K-ras-2 and loss of heterozygosity mutational analysis had a much lower sensitivity at 33% and 50% respectively., Conclusions: Consistency in histology, CEA levels, and K-ras-2 and loss of heterozygosity mutations was seen in only 35% of cases, all of which were benign cysts. In the detection of malignant cysts, elevated CEA levels were more predictive of histology in comparison to K-ras-2 or loss of heterozygosity mutations. Additionally, false positivity of loss of heterozygosity mutations was noted to be considerably higher than K-ras-2 mutations or even fluid CEA levels. These findings suggest that DNA mutation analysis should not be used routinely but rather selectively in the evaluation of pancreatic cysts.

Diarrhea and weight loss are common after pancreaticoduodenectomy, and arise from varying etiologies. An uncommon but important cause for these symptoms is the postoperative activation of silent celiac disease. We sought to describe the clinical presentation, diagnosis, treatment, and follow-up of a series of patients with silent celiac disease unmasked after pancreaticoduodenectomy, and to summarize the existing case reports on this association. A search of the electronic medical record at our institution was performed cross-referencing terms associated with celiac disease and pancreaticoduodenectomy for the years 1976-2004. Cases were then reviewed to ensure that no signs or symptoms attributable to celiac disease were present preoperatively. Seven patients were identified; five were male, and the median age was 56. All patients underwent surgery for a presumed pancreatic or ampullary malignancy. Six patients developed symptoms ultimately attributable to celiac disease immediately after pancreaticoduodenectomy, most commonly diarrhea and weight loss. A single patient had silent celiac disease incidentally diagnosed at pancreaticoduodenectomy that remained silent postoperatively on an unrestricted diet. Symptoms completely resolved in 4 of 6 patients after initiation of a gluten-free diet, with partial improvement in the remaining 2 patients. The median delay from pancreaticoduodenectomy to diagnosis of celiac disease in the 6 symptomatic patients was 6 months. Clinicians should consider celiac disease as a potential diagnosis in patients with failure to thrive and diarrhea after pancreaticoduodenectomy. This entity is uncommon, but may be under-recognized. The underlying mechanism may relate to an increased antigenic load secondary to postsurgical changes in intestinal physiology.

Roux-en-Y gastric bypass (RYGBP) is the most commonly performed bariatric operation in the USA. In the early postoperative stage, gastrointestinal (GI) bleeding is an infrequent but potentially serious complication that usually results from bleeding at the gastrojejunostomy staple-line. Observant management with transfusion for stable patients and surgical exploration for unstable patients is typically recommended for early GI bleeding. We hypothesized that use of endoclips, which do not cause thermal injury to the surrounding tissues (or anastomosis), may be preferable to thermal approaches which could cause tissue injury. We report 2 cases of early GI bleeding after RYGBP that were successfully managed with endoclip application to bleeding lesions. Emergent endoscopy was performed, and major stigmata such as active spurting vessel and adherent clot were noted at the gastrojejunostomy staple-lines. Endoscopic hemostasis using endoclips was readily applied to bleeding lesions at staple-lines. Primary hemostasis was achieved, and there was no recurrent bleeding or complication. We conclude that therapeutic endoscopy can be performed safely for early bleeding after RYGBP. In patients with early bleeding after RYGBP, use of endoclips is mechanistically preferable to other options.