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Background: Patients should be informed beforehand of the risk factors for exocrine pancreatic insufficiency (ExoPI) after pancreatic surgery; however, there are no clear identified risk factors for this condition. This study aimed to identify the preoperative, perioperative and postoperative risk factors for ExoPI after pancreatic surgery., Methods: We conducted a systematic search of PubMed, Scopus, SAGE, CINAHL Plus and Taylor & Francis from inception to Mar. 7, 2021, for full-text articles that included patients who had undergone pancreatic surgery. The primary outcome was the number of ExoPI events and any risk factors evaluated. We used the Newcastle-Ottawa Scale to assess study quality., Results: Twenty studies involving 4131 patients (2312 [52.3%] male, mean age 60.12 [standard deviation 14.07] yr) were included. Of the 4131 patients, 1651 (40.0%) had postoperative ExoPI. Among the 11 factors evaluated, the significant risk factors were preoperative main pancreatic duct (MPD) diameter greater than 3 mm (odds ratio [OR] 4.50, 95% confidence interval [CI] 1.06-19.05), pancreaticoduodenectomy (PD) as the surgical treatment procedure (OR 3.31, 95% CI 1.92-5.68), pancreaticogastrostomy (PG) as the anastomotic procedure (OR 3.13, 95% CI 1.83-5.35), hard pancreatic texture (OR 2.93, 95% CI 1.99-4.32) and adjuvant chemotherapy (OR 2.50, 95% CI 1.54-4.04). Gender, history of diabetes mellitus or endocrine pancreatic insufficiency (EndoPI), underlying diseases, de novo diabetes or EndoPI, pylorus-preserving PD and postoperative pancreatic fistula were not risk factors for ExoPI after pancreatic surgery., Conclusion: Preoperative MPD diameter greater than 3 mm, PD, PG reconstruction, hard pancreatic texture and adjuvant chemotherapy were risk factors for the development of ExoPI after pancreatic surgery. The findings should provide useful information for patients to reduce postoperative dissatisfaction and improve quality of life., Competing Interests: Competing interests: None declared., (© 2022 CMA Impact Inc. or its licensors.)

Background and Aims: Several studies have shown improved short-term outcome with endoscopic transmural drainage and necrosectomy for the treatment of walled-off pancreatic necrosis. However, knowledge on the long-term prognosis after such treatment is limited. The aim of present study was to evaluate long-term outcomes in patients endoscopically treated with transmural drainage and necrosectomy., Methods: We retrospectively follow up 125 patients with walled-off pancreatic necrosis treated with endoscopic transmural drainage and necrosectomy in 2010-2017. All patients received plastic pigtail stents and nasocystic catheter. Additional external drainage was performed in 41 patients. Main outcomes were survival, pancreatic function, development of co-morbidities, ability to work and social status., Results: During a median follow-up of 4.3 years, nine (7%) patients died. Seven deaths were unrelated to pancreatic disease, and two patients died of pancreatic cancer. Twenty-two (18%) patients developed exocrine pancreatic insufficiency. Thirty-six (32%) previous non-diabetics developed endocrine insufficiency. Endoscopic necrosectomy during admission (odds ratio (OR) = 1.28, 95% confidence interval (CI) 1.05-1.56; p  = 0.015) and therapy on the main pancreatic duct (OR = 8.08, 95% CI 2.43-26.9; p  < 0.001) during follow-up predicted development of exocrine insufficiency. Severity on computed tomography predicted endocrine insufficiency (OR = 1.61, 95% CI 1.24-2.09; p  < 0.001). Most patients regained their working capacity and preserved their marital status., Conclusions: This study provides robust data on the long-term outcome of patients with walled-off pancreatic necrosis treated with endoscopic transmural drainage and necrosectomy. The favourable outcomes on survival, pancreatic function and social status support current recommendations of endoscopic transmural drainage and necrosectomy being the treatment of choice for walled-off pancreatic necrosis.

Background: Only few studies have been conducted on pancreatic diabetes and data from large epidemiological studies are missing. Our main objective was to study the most important differences and similarities between pediatric individuals with pancreatic diabetes and type 1 diabetes (T1D)., Methods: Patients <20 years of age were identified from the diabetes patient follow-up registry (DPV). Data of the most recent treatment year between January 2000 and March 2018 were aggregated. Propensity score was used to match individuals with pancreatic diabetes to individuals with T1D. Matching was conducted one-to-one by sex, age, diabetes duration, body mass index SD score (BMI-SDS), and migration background., Results: We studied 731 individuals with pancreatic diabetes and 74 460 with T1D. In the matched cohort of 631 pairs, HbA1c was significantly lower in pancreatic diabetes (7.4% [95% confidence interval: 7.2; 7.5%]) compared to T1D patients (8.7% [8.5; 8.8%]). Daily insulin dose (0.80 IU/kg [0.77; 0.84] vs 0.86 IU/kg [0.82; 0.90]) and insulin pump use (13.3% [10.7; 16.4] vs 22.1% [19.0; 25.6%]) were lower in patients with pancreatic diabetes. However, event rates of severe hypoglycemia were similar between pancreatic and T1D patients (8.8 [5.4; 14.2] vs 9.6 [5.9; 15.6] events per 100 patient years)., Conclusions: With the use of robust epidemiological data, our study improves the knowledge on clinical characteristics in pediatric individuals with pancreatic diabetes. Moreover, our results serve as a basis to reconsider treatment options and for discussing clinical practice guidelines for patients with this rare medical condition., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: In collaboration with United European Gastroenterology, the working group on 'Harmonizing diagnosis and treatment of chronic pancreatitis across Europe' (HaPanEU) developed European guidelines for the management of chronic pancreatitis using an evidence-based approach., Methods: Recommendations of multidisciplinary review groups based on systematic literature reviews to answer predefined clinical questions are summarised. Recommendations are graded using the Grading of Recommendations Assessment, Development and Evaluation system., Results: Recommendations covered topics related to the clinical management of chronic pancreatitis: aetiology, diagnosis of chronic pancreatitis with imaging, diagnosis of pancreatic exocrine insufficiency, surgical therapy, medical therapy, endoscopic therapy, treatment of pancreatic pseudocysts, pancreatic pain, nutrition and malnutrition, diabetes mellitus and the natural course of the disease and quality of life., Conclusions: The HaPanEU/United European Gastroenterology guidelines provide evidence-based recommendations concerning key aspects of the medical and surgical management of chronic pancreatitis based on current available evidence. These recommendations should serve as a reference standard for existing management of the disease and as a guide for future clinical research. This article summarises the HaPanEU recommendations and statements., (Copyright © 2018. Published by Elsevier B.V.)

Background: Mycophenolic acid (MPA), either given as an ester pro-drug or as an enteric-coated sodium salt, is the most commonly prescribed anti-proliferative immunosuppressive agent used following organ transplantation and widely applied in immune-mediated diseases. Clinicians are well aware of common adverse reactions related to MPA treatment, in particular diarrhea, leukopenia and infections. Here we report a case of severe, persistent ascites associated with MPA treatment. The otherwise unexplained and intractable ascites, requiring repeated paracenteses for more than 8 months, rapidly ceased with stopping the MPA treatment. To our knowledge this is the first case of severe ascites associated with MPA treatment reported in the scientific literature., Case Presentation: A 45-year old female with type 1 diabetes mellitus received a simultaneous kidney-pancreas transplant. The surgery was uneventful. However, post-operatively she developed severe transudative ascites requiring in total more than 40 paracenteses treatments draining in the average 2.8 l of ascites fluid. The ascites formation persisted despite exclusion of a surgical complication, fully functioning kidney and pancreas allografts, lack of any significant proteinuria, normalization of circulating albumin levels, intensive use of diuretics and deliberate attempts to increase the intervals between the paracentesis treatments. Various differential diagnoses, including infectious, hepatic, vascular and cardiac causes were ruled out. Nine months after surgery enteric-coated mycophenolate sodium was switched to azathioprine after which ascites completely resolved. When mycophenolate was recommenced abdominal fullness and weight gain reoccurred. The patient had to be switched to long-term azathioprine treatment. More than 1 year post-conversion the patient remains free of ascites., Conclusion: MPA is the most widely used antimetabolite immunosuppressive agent. We suggest to consider MPA treatment in the differential diagnosis of severe and unexplained ascites in transplant and non-transplant patients.

Objectives: Total pancreatectomy (TP) is associated with postoperative endocrine and exocrine insufficiency. Especially, insulin therapy reduces quality of life and may lead to long-term complications. We review the literature with regard to the potential option of pancreas transplantation alone (PTA) after TP in patients with chronic pancreatitis or benign tumors., Methods: A MEDLINE search (1958-2013) using the terminologies pancreas transplantation, pancreas transplantation alone, total pancreatectomy, morbidity, mortality, insulin therapy, and quality of life was performed. In addition, the current book and congress publications were reviewed., Results: Total pancreatectomy after benign and borderline tumors as well as chronic pancreatitis is continuously increasing. Despite improvement of exogenous insulin therapy, more than 50% of these patients experience severe glucose control problems, which cause up to 50% long-term mortality. Pancreas transplantation alone can cure both endocrine and exocrine insufficiency and reduce the associated risks. The 3-year graft and patient survival rates after PTA are up to 73% and 100%, respectively., Conclusions: Pancreas transplantation alone after TP in patients with pancreatitis or benign tumors improves the recipient's quality of life and reduces long-term mortality. Considering the amount of available organs and potential candidates, PTA can be a treatment option for patients after TP with chronic pancreatitis or benign tumors.

In this report, we address the issue of allogeneic stem cell transplantation in children with congenital neutropenia. Constitutional disorders with neutropenia are exceptional. Treatment and prevention of severe infections are a major concern in the management of chronic neutropenia. These disorders, especially Kostmann's disease and Shwachman-Bodian-Diamond syndrome, are associated with an increased risk of leukemia. The role of allogeneic stem cell transplantation in these patients is still unclear. In an effort to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the fourth annual series of workshops which brought together practitioners from all member centers and took place in September 2013 in Lille., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Hypothesis: Because of better survival following pancreaticoduodenectomy (PD), patients may develop complications due to PD and not due to malignancy per se. Exocrine insufficiency may be related to pancreatic duct obstruction or strictures attributable to duct-to-mucosa anastomosis, as in pancreaticojejunostomy. We propose a technique of managing a post-PD duct obstruction., Design: Retrospective review from September 2005 to August 2008., Setting: Methodist Dallas Medical Center, Dallas, Texas, a referral, high-volume, nonuniversity tertiary care center., Patients: All patients who underwent surgery for anastomotic pancreaticojejunal stricture., Main Outcome Measures: Perioperative outcomes., Results: All the patients were women and aged 62, 78, and 45 years. Comorbidities were documented in 2 patients. Two patients presented with severe acute abdominal pain and hyperamylasemia while 1 was asymptomatic. Two patients underwent magnetic resonance cholangiopancreatography with secretin stimulation. Endoscopic retrograde cholangiopancreatography was attempted in 1 patient. Operating time was 99 minutes, 158 minutes, and 154 minutes. Estimated blood loss was 250 mL, 400 mL, and 500 mL. A single-layer, side-to-side pancreaticogastrostomy was performed as the drainage procedure in all patients. There was no mortality associated with any of the patients within 30 days. Morbidity was seen only in 1 patient. None of the patients needed a reoperation. The mean length of hospital stay was 9 days. All patients were asymptomatic for pain., Conclusion: We propose a durable technique for treating pancreatic ductal strictures post-PD that appears to result in superior postoperative outcome.

Characteristic symptoms of chronic pancreatitis are difficult to manage conservatively. They include severe pain and endocrine and exocrine insufficiency. Surgical treatment with simple and extended draining procedures addresses pain relief and the management of chronic pancreatitis-associated complications of adjacent organs. Following the assumption that pancreatic duct changes with intraductal hypertension are the reason for pain, simple drainage procedures have reduced pain in up to 80% of patients, with low morbidity and mortality. In case of complications involving adjacent organs with inflammatory pancreatic head tumor and stenosis of the distal bile duct, extended drainage procedures with limited pancreatic head resection according to Frey and V-shaped excision of the ventral aspect of the pancreas have been performed successfully.

In chronic pancreatitis chronic pain is the most frequent indication for surgery. Because symptoms are often caused or maintained by an inflammatory mass in the head of the pancreas, resection procedures are superior to pure surgical drainage. The pancreatoduodenectomy (PD) and the duodenum-preserving pancreatic head resection (DPPHR) are safe and effective techniques resulting in long-lasting pain relief in about 80% of patients. Randomized controlled trials (RCTs) show initial functional advantages for the organ-preserving DPPHR compared to PD, but these advantages are lost during follow-up, most likely because neither operation prevents a progressive loss of exocrine and endocrine function. Nevertheless the less invasive DPPHR should be regarded as the procedure of choice. The technique of DPPHR described by Beger was modified by Frey to an extended drainage procedure with local head excision; the Berne modification offers a technically less demanding option with comparable extent of resection. While results in terms of pain relief, quality of life and organ function are comparable between the three DPPHR techniques, the technical aspect of a simpler procedure favors the Berne modification.

Background & Aims: Neonatal intestinal obstruction (meconium ileus [MI]) occurs in 15% of patients with cystic fibrosis (CF). Our aim was to determine the relative contribution of genetic and nongenetic modifiers to the development of this major complication of CF., Methods: A total of 65 monozygous twin pairs, 23 dizygous twin/triplet sets, and 349 sets of siblings with CF were analyzed for MI status, significant covariates, and genome-wide linkage., Results: Specific mutations in the CF transmembrane conductance regulator (CFTR), the gene responsible for CF, correlated with MI, indicating a role for CFTR genotype. Monozygous twins showed substantially greater concordance for MI than dizygous twins and siblings (P = 1 x 10(-5)), showing that modifier genes independent of CFTR contribute substantially to this trait. Regression analysis revealed that MI was correlated with distal intestinal obstruction syndrome (P = 8 x 10(-4)). Unlike MI, concordance analysis indicated that the risk for development of distal intestinal obstruction syndrome in CF patients is caused primarily by nongenetic factors. Regions of suggestive linkage (logarithm of the odds of linkage >2.0) for modifier genes that cause MI (chromosomes 4q35.1, 8p23.1, and 11q25) or protect from MI (chromosomes 20p11.22 and 21q22.3) were identified by genome-wide analyses. These analyses did not support the existence of a major modifier gene on chromosome 19 in a region previously linked to MI., Conclusions: The CFTR gene along with 2 or more modifier genes are the major determinants of intestinal obstruction in newborn CF patients, whereas intestinal obstruction in older CF patients is caused primarily by nongenetic factors.

Pancreatic digestive insufficiency is a common problem in both Type 1 and Type 2 diabetes and remains a serious consequence of diabetes in developing countries. The problem is not corrected by supportive therapies including exogenous insulin injections. It is our hypothesis that digestive insufficiency may be corrected or diminished by the transplantation of islets to the pancreas, thereby supplying islet hormones directly to acinar tissue analogous to the normal pancreas. Diabetic rats received 1000 syngeneic islets and dogs received 7600 autologous islets per kilogram as a transplant to the pancreas. Blood glucose and amylase concentrations were normalized in islet recipients in contrast with controls receiving no islets or islets transplanted to the renal capsule. These results suggest that diabetic digestive insufficiency may be corrected by intrapancreatic islet transplantation.

This report assessed the results of allogeneic stem cell transplantation (allo-SCT) in 26 patients with Shwachman-Diamond disease (SDS) and severe bone marrow abnormalities. The conditioning regimen was based on busulphan (54%), total body irradiation (23%), fludarabine (15%) or other chemotherapy combinations (8%). Standard prevention of graft versus host disease (GVHD) with cyclosporin +/- methotrexate was adopted in 54% of the patients whilst in vivo or in vitro T-cell depletion was used in 17 and four patients respectively. Neutrophil and platelet engraftment were achieved in 21 (81%) and 17 (65%) of 26 patients after a median time of 18 days and 29 days respectively. The incidence of grade III and IV acute GVHD was 24% and of chronic GVHD 29%. Nine patients died after a median time of 70 d, post-SCT. After a median follow-up of 1.1 years, the transplant-related mortality was 35.5% (95% CI 17-54) whilst the overall survival was 64.5% (95% CI 45.7-83.2). Allo-SCT was found to be successful in more than half of SDS patients with severe bone marrow dysfunction. Further improvements would be anticipated by a better definition of the optimum time in the course of disease to transplant and by the adoption of less toxic conditioning regimens.

Background: Total pancreatectomy to treat chronic pancreatitis is associated with severe diabetic control problems in 15% to 75% of patients, causing up to 50% of deaths late postoperatively. We report our experience with islet autotransplants at the time of, or with pancreas allotransplants after, total pancreatectomy., Study Design: Between February 1, 1977, and June 30, 2003, we performed 112 islet autotransplants at the time of total pancreatectomy; we also performed 20 pancreas allotransplants in 13 patients who had already undergone total pancreatectomy months to years earlier., Results: Islet autotransplants at the time of total pancreatectomy in patients who had not had previous operations on the body and tail of the pancreas were associated with a high islet yield (>2,500 islet equivalents/kg body weight), and >70% of the recipients achieved complete insulin independence. In contrast, a previous distal pancreatectomy or a Puestow drainage procedure was associated with a low islet yield in 75% of them and with complete insulin independence in <20%. A pancreas allotransplant after total pancreatectomy was not associated with any transplant-related mortality at 1 and 3 years posttransplant. The pancreas graft survival rate at 1 year posttransplant was 77% with tacrolimus-based immunosuppression (versus 67% with cyclosporine). Enteric (over bladder) drainage was preferred to manage exocrine graft secretions, to cure pancreatectomy-induced endocrine and exocrine insufficiency., Conclusions: Our series shows that pancreas allotransplants can be performed without transplant-related mortality and, when tacrolimus-based immunosuppression is used, with 1-year pancreas graft survival rates >75%. In contrast to a simultaneous islet autotransplant, a pancreas allotransplant has the disadvantage of requiring lifelong immunosuppression, but the advantage of not only curing endocrine but also exocrine insufficiency. Both transplant options, if successful, improve the recipient's quality of life.

Background and Aims: We have observed intraductal papillary mucinous neoplasm (IPMN) associated with pancreatic calcification. The aim of this study is to describe the profile of IPMN associated with calcification and gain insights into the pathogenesis of calcification in IPMN., Methods: We identified 10 patients with IPMN with pancreatic calcification, of whom 7 underwent pancreatic resection. We reviewed demographic data, history of previous pancreatitis, and radiological and histological features of these patients., Results: In patients with IPMN with calcification (mean age, 65 +/- 12 yr; 50% men), a diagnosis of chronic calcifying pancreatitis was entertained in 5 of 10 patients; 2 patients had undergone previous endoscopic therapy for stone removal. There was no previous history of pancreatitis in 9 of 10 patients. Radiologically, calcifications were seen diffusely throughout the gland in 8 of 10 patients and interpreted as chronic calcific pancreatitis. Although 1 of the 7 patients who underwent resection had diffuse IPMN throughout the gland, 6 patients had IPMN confined to the head or uncinate process (mean size, 2.75 cm; range, 1.1-5 cm). Histologically, 6 of 7 IPMNs were adenomas, and 1 patient had invasive cancer. No patient had intratumoral calcification. All 7 patients had calcification within the main pancreatic duct and/or side branches, often within inspissated mucus., Conclusions: IPMN associated with pancreatic calcification can lead to misdiagnosis and inappropriate treatment for chronic calcifying pancreatitis. In the absence of intratumoral calcification or a previous history of long-standing chronic pancreatitis, calcification in IPMN likely represents a unique and hitherto unrecognized form of calcifying obstructive pancreatitis caused by prolonged partial obstruction of the pancreatic duct.

Background: Duodenum-preserving resection of the head of the pancreas (DPRHP) is performed in patients with chronic pancreatitis (CP) localized in the head of the pancreas. It has been suggested that functional integrity of the upper digestive tract is preserved after DPRHP. We tested this hypothesis with regard to gallbladder motility., Methods: Gallbladder motility and cholecystokinin (CCK) secretion were studied fasting, after cephalic vagal stimulation with sham feeding, and after regular feeding in 9 patients after DPRHP, in 6 unoperated patients with CP, and 9 healthy control subjects., Results: Mean fasting gallbladder volume in patients after DPRHP (49 +/- 10 cm3) and patients with CP (53 +/- 10 cm3) was larger than in controls (33 +/- 3 cm3). Sham-feeding gallbladder contraction did not differ between patients after DPRHP, patients with CP, and controls. Both postprandial CCK secretion and gallbladder contraction in patients after DPRHP (78 +/- 16 pM. 120 min; 47% +/- 6%) and patients with CP (72 +/- 18 pM.120 min; 40% +/- 7%) were significantly reduced (P < 0.05) compared with controls (151 +/- 13 pM.120 min; 74% +/- 4%). Fasting gallbladder volume, sham feeding, and regular-feeding-induced gallbladder contraction and postprandial CCK secretion did not differ between operated and unoperated patients with CP., Conclusions: Gallbladder motility and CCK secretion are reduced in patients with pancreatic insufficiency. A DPRHP procedure does not further influence these results. These findings support the concept that gallbladder motor function is preserved after DPRHP.

The natural course of the classical symptoms of chronic pancreatitis, i.e. pain, exocrine and endocrine pancreatic insufficiency, was followed up in 335 patients over a median of 9.8 years (mean 11.3 +/- 8.3 years). Pain relief was not obtained in the majority of patients, even after a longterm observation of > 10 years, and severe exocrine and/or endocrine insufficiency, severe duct abnormalities and pancreatic calcifications developed. Alcohol abstinence failed to have a significant beneficial effect on pain. Pancreatic surgery led to pain relief immediately after operation, but later on the pain course between operated and nonoperated patients was not significantly different. Repeated exocrine pancreatic function tests in 143 patients showed that functional exocrine impairment came to a standstill (46%), or improved (11%). At the end of the observation, 22% of 335 patients still had normal endocrine function and only 40% required insulin treatment. Alcohol abstinence had a significant beneficial effect on endocrine, but not on exocrine pancreatic insufficiency. Chronic pancreatitis led to a sharp increase in unemployment and retirement. Pancreatic carcinoma occurred in 3% and extrapancreatic carcinoma in 4%. The mortality rate within the observation period was 22%, pancreatitis-induced complications accounted for 13% of these deaths.

The effects of exocrine pancreatic insufficiency on the small intestinal mucosa were examined in dogs following pancreatic duct ligation. There were no significant changes either in villus architecture or enterocyte height after duct ligation, but numbers of bacteria in duodenal juice increased then subsequently decreased following treatment with exogenous pancreatic enzymes. Pancreatic insufficiency resulted in a considerable increase in the proportion of microvillar membrane proteins of molecular mass over 200 kDa from 3.3 +/- 4 per cent (mean +/- SEM) to 13.6 +/- 7.2 per cent, and this decreased to 6.9 +/- 5.2 per cent following pancreatic enzyme supplementation. However, anticipated increases in activities of maltase and sucrase were not observed following duct ligation, and there was a reduction in lactase activity which was reversed by pancreatic supplementation. Activities of marker enzymes for the other subcellular organelles showed relatively minor or no changes throughout the study. These findings are consistent with a specific role for pancreatic enzymes in the post-translational processing of intestinal microvillar membrane proteins, and suggest that reduced degradation of brush border proteins in the absence of pancreatic secretions may be masked by quantitative and qualitative changes in the intestinal microflora.