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Background Iatrogenic bile duct injury (IBDI) is a challenging surgical complication. IBDI management can be guided by artificial intelligence models. Our study identified the factors associated with successful initial repair of IBDI and predicted the success of definitive repair based on patient risk levels. Methods This is a retrospective multi-institution cohort of patients with IBDI after cholecystectomy conducted between 1990 and 2020. We implemented a decision tree analysis to determine the factors that contribute to successful initial repair and developed a risk-scoring model based on the Comprehensive Complication Index. Results We analyzed 748 patients across 22 hospitals. Our decision tree model was 82.8% accurate in predicting the success of the initial repair. Non-type E (p p p Discussion Machine learning algorithms for IBDI are a novel tool may help to improve the decision-making process and guide management of these patients.

BACKGROUND: Pancreatectomy plus celiac axis resection (CAR) is performed in patients with locally advanced pancreatic cancer. The morbidity rates are high, and no survival benefit has been confirmed. It is not known at present whether it is the type of pancreatectomy, or CAR itself, that is the reason for the high complication rates.; METHODS: Observational retrospective multicenter study.; INCLUSION CRITERIA: patient undergoing TP, PD or DP plus CAR for a pancreatic cancer.; RESULTS: Sixty-two patients who had undergone pancreatic cancer surgery (PD,TP or DP) plus CAR were studied. Group 1: 17 patients who underwent PD/TP-CAR (13TP/4PD); group 2: 45 patients who underwent DP-CAR. Groups were mostly homogeneous. Operating time was longer in the PD/TP group, while operative complications did not differ statistically in the two groups. The number of lymph nodes removed was higher in the PD/TP group (26.5 vs 17.3), and this group also had a higher positive node ratio (17.9% vs 7.6%). There were no statistical differences in total or disease-free survival between the two groups.; CONCLUSION: It seems that CAR, and not the type of pancreatectomy, influences morbidity and mortality in this type of surgery. International multicenter studies with larger numbers of patients are now needed to validate the data presented here.

Background and objectives Postoperative complications (POCs) after hepatic resection for colorectal liver metastases (CRLM) adversely affect long-term survival. The aim of this study was to analyze the effect of POC etiology and severity on overall survival (OS) and disease-free survival (DFS). Methods A retrospective study of 254 consecutive hepatectomies for CRLM was performed. Univariate and multivariate analyses were performed to determine the effects of demographic, tumor-related and perioperative variables on OS and DFS. A 1:1 propensity score matching (PSM) was then used to compare patients with different POC etiology: infective (Inf-POC), noninfective (Non-inf POC), and no-complications (No-POC). Results Inf-POC, Non-inf POC, and No-POC patients represented 18.8%, 19.2%, and 62% of the sample, respectively. In univariate and multivariate analyses infectious POC were independent risk factors for decreased OS and DFS. After PSM, Inf-POC group presented decreased OS and DFS when compared with Non-inf POC (5-year OS 31.8% vs 51.6%; P = .05 and 5-year DFS 13.6% vs 31.9%; P = .04) and with No-POC (5-year OS 29.4% vs 58.7%; P = .03 and 5-year DFS 11.8% vs 39.7%; P = .03). There were no differences between Non-inf POC and No-POC patients. POC severity calculated using the Comprehensive Complications Index did not influence OS and DFS before and after PSM. Conclusion The negative oncological impact of POCs after CRLM resection is determined by infective etiology not by severity.

Objective To investigate whether percutaneous cholecystostomy (PC) for the treatment of acute calculous cholecystitis (ACC) has better results than emergency cholecystectomy (EC) in elderly and high-risk surgical patients. Methods Patients >= 70 years and/or >= ASA-PS 3 with ACC treated with PC or EC between 2005 and 2016 were retrospectively reviewed. Both techniques were compared regarding morbi-mortality, hospital stay, complications and readmissions. A subgroup analysis in higher risk patients (>= 70 years plus >= ASA-PS 3) was also performed. A binary logistic regression analysis for outcome variables to calculate the OR was carried out. Results A total of 461 patients were included in the study. The results of PC were worse compared to EC: 30-day mortality (8.6 vs. 1.7%, OR 18.4), 90-day mortality (10.4 vs. 2.1%, OR 10.3), length of stay (days) (13.21 +/- 8.2 vs. 7.48 +/- 7.67, OR 8.7) and readmission rate (35.1 vs. 12.6%, OR 4.7). Complications were lower for PC (14 vs. 22.6%, OR 0.41), but there were no significant differences in the number of severe complications (Clavien-Dindo >= III). Higher-risk subgroup analysis (n = 193; PC = 128, EC = 65) showed similar results to the whole series. Patients with ACC for more than 3 days had more risk of severe complications in both groups (OR 2.26; OR 2.76). Conclusion PC was associated with an increased risk of mortality at 30 and 90 days, more readmissions and longer hospital stay. Although PC presents a lower risk of complications, the percentage of severe complications (Clavien-Dindo >= III) does not show significant differences.

We present the case of a 76-year-old male with a history of acute cholecystitis who underwent a scheduled laparoscopic cholecystectomy. Chronic cholecystitis with a thickened cystic duct was observed intraoperatively. The anatomic pathology report found high-grade dysplasia that affected the distal edge of the cystic duct. In view of these findings, an endoscopic retrograde cholangiopancreatography (ERCP) was performed with SpyGlass® and an excrescent lesion suggestive of malignancy adjacent to the cystic-common bile duct junction was observed. A resection of the extrahepatic bile duct was performed with lymphadenectomy of the hepatic hilum and hepaticojejunostomy in a subsequent procedure. The definitive pathology report confirmed pancreaticobiliary intraductal papillary mucinous neoplasia with high-grade dysplasia and free margins.

BackgroundNeoadjuvant therapy (NAT) for pancreatic adenocarcinoma (PDAC) patients has shown promising results in non-randomized trials. This is a multi-institutional phase II trial of NAT in resectable PDAC patients.MethodsPatients with confirmed resectable PDAC after agreement by two expert radiologists were eligible. Patients received three cycles of GEM (1000mg/m(2)/week) plus daily erlotinib (ERL) (100mg/day). After re-staging, patients without progressive disease underwent 5 weeks of therapy with GEM (300mg/m(2)/week), ERL 100mg/day and concomitant radiotherapy (45Gy). Efficacy was assessed using tumor regression grade (TRG) and resection margin status. Using a single-arm Simon's design, considering the therapy not useful if R070% (alpha 5%, beta 10%), 24 patients needed to be recruited. This trial was registered at ClinicalTrials.gov, number NCT01389440.ResultsTwenty-five patients were enrolled. Adverse effects of NAT were mainly mild gastrointestinal disorders. Resectability rate was 76%, with a R0 rate of 63.1% among the resected patients. Median overall survival (OS) and disease-free survival (DFS) were 23.8 (95% CI 11.4-36.2) and 12.8 months (95% CI 8.6-17.1), respectively. R0 resection patients had better median OS, compared with patients with R1 resection or not resected (65.5 months vs. 15.5 months, p=0.01). N0 rate among the resected patients was 63.1%, and showed a longer median OS (65.5 vs. 15.2 months, p=0.009).ConclusionThe results of this study confirm promising oncologic results with NAT for patients with resectable PDAC. Therefore, the present trial supports the development of phase II randomized trials comparing NAT vs. upfront surgery in resectable pancreatic cancer.

Pancreatic neuroendocrine tumors represent less than 5% of all pancreatic tumors. They are a heterogeneous group of neoplasms with a diverse behavior and prognosis. Pancreatic vasoactive intestinal polypeptide tumor (VIPoma) is an exceptional tumor within this group due to its low incidence. The presence of pancreatic VIPoma should be clinically suspected in all patients with watery diarrhea, particularly when accompanied by a loss of potassium and bicarbonate and a pancreatic mass on imaging. There are other pathologies with similar symptoms; therefore, a correct differential diagnosis with an adequate treatment is essential for its management. We present the case of a 46-year-old patient who developed a prerenal kidney failure secondary to severe watery diarrhea after a diagnosis of pancreatic VIPoma. Thus, a resection was performed as the patient was rapidly deteriorating and required an intervention.

espanolIntroduccion: la lesion yatrogenica de la via biliar (LYVB) es una complicacion con elevada morbilidad tras la colecistectomia. En los ultimos anos la endoscopia ha adquirido un papel fundamental en el manejo de esta patologia. Metodos: estudio retrospectivo de LYVB tras colecistectomia abierta (CA) o colecistectomia laparoscopica (CL) tratadas en nuestro centro entre 1993 y 2017. Se analizaron los datos referentes a las caracteristicas clinicas, tipo de lesion segun la clasificacion de Strasberg-Bismuth, diagnostico, tecnica de reparacion y seguimiento. Resultados: se estudian 46 pacientes. La incidencia LYVB fue de 0,48%, 0,61% para las CL y 0,24% para las CA. El diagnostico se realizo de forma intraoperatoria en 12 casos (26%) y mediante colangiopancreatografia retrograda endoscopica (CPRE) en 10 (21,7%). Las caracteristicas mas comunes a todos los pacientes con LYVB fueron la colecistitis aguda (20/46, 43,5%), ingreso previo por patologia biliar (16/46, 43,2%) y realizacion de CPRE previa a la colecistectomia (7/46, 18,9%). Los tipos de LYVB mas frecuentes fueron el D (17/46, 36,9%) y el A (15/46, 32,6%). El tratamiento mas empleado fue sutura primaria (13/46, 28,3%) seguido de CPRE (11/46, 23,9%) con esfinterotomia y/o endoprotesis. Ademas, la CPRE se utilizo en el postoperatorio inmediato de 6 pacientes (13%) con reparacion quirurgica de la LYVB para solucionar complicaciones inmediatas. Conclusion: la CPRE es util en el manejo de la LYVB no diagnosticada intraoperatoriamente. Permite localizar la zona lesionada de la via biliar, realizar maniobras terapeuticas y tratar de manera satisfactoria algunas complicaciones postoperatorias. EnglishIntroduction: iatrogenic bile duct injury (IBDI) is a complication with a high morbidity after cholecystectomy. In recent years, endoscopy has acquired a fundamental role in the management of this pathology. Methods: a retrospective study of IBDI after open cholecystectomy (OC) or laparoscopic cholecystectomy (LC) of patients treated in our center between 1993 and 2017 was performed. Clinical characteristics, type of injury according to the Strasberg-Bismuth classification, diagnosis, repair techniques and follow-up were analyzed. Results: 46 patients were studied and IBDI incidence was 0.48%, 0.61% for LC and 0.24% for OC. A diagnosis was made intraoperatively in 12 cases (26%) and by endoscopic retrograde cholangiopancreatography (ERCP) in 10 (21.7%) cases. The most common IBDI patient characteristics were acute cholecystitis (20/46, 43.5%), previous admission due to biliary pathology (16/46, 43.2%) and ERCP prior to cholecystectomy (7/46, 18.9%). The most frequent types of IBDI were D (17/46, 36.9%) and A (15/46, 32.6%). The most commonly used treatment was primary suture (13/46, 28.3%) followed by ERCP (11/46, 23.9%) with sphincterotomy and/or stents. In addition, ERCP was performed during the immediate postoperative period in 6 (13%) patients with a surgical IBDI repair in order to resolve immediate complications. Conclusion: ERCP is useful in the management of IBDI that is not diagnosed intraoperatively. This procedure facilitates the localization of the injured area of the bile duct, therapeutic maneuvers and successful outcomes in postoperative complications.

Objective: To provide evidence-based recommendations for the management of exocrine pancreatic insufficiency (EPI) after pancreatic surgery. Background: EPI is a common complication after pancreatic surgery but there is certain confusion about its frequency, optimal methods of diagnosis, and when and how to treat these patients. Methods: Eighteen multidisciplinary reviewers performed a systematic review on 10 predefined questions following the GRADE methodology. Six external expert referees reviewed the retrieved information. Members from Spanish Association of Pancreatology were invited to suggest modifications and voted for the quantification of agreement. Results: These guidelines analyze the definition of EPI after pancreatic surgery, (one question), its frequency after specific techniques and underlying disease (four questions), its clinical consequences (one question), diagnosis (one question), when and how to treat postsurgical EPI (two questions) and its impact on the quality of life (one question). Eleven statements answering those 10 questions were provided: one (9.1%) was rated as a strong recommendation according to GRADE, three (27.3%) as moderate and seven (63.6%) as weak. All statements had strong agreement. Conclusions: EPI is a frequent but under-recognized complication of pancreatic surgery. These guidelines provide evidence-based recommendations for the definition, diagnosis, and management of EPI after pancreatic surgery.

Background Since the Atlanta Symposium several guidelines and consensus conferences have been published to improve the management and understanding of patients with acute pancreatitis. Herein, a review of the most recent guidelines on acute pancreatitis is carried out, trying to find differences and similarities.

Background Anastomotic leakage of pancreaticojejunostomy (PJ) remains the single most important source of morbidity after pancreaticoduodenectomy (PD). The primary aim of this randomized clinical trial comparing PG with PJ after PD was to test the hypothesis that invaginated PG would result in a lower rate and severity of pancreatic fistula. Methods Patients undergoing PD were randomized to receive either a duct-to-duct PJ or a double-layer invaginated PG. The primary endpoint was the rate of pancreatic fistula, using the definition of the International Study Group on Pancreatic Fistula. Secondary endpoints were the evaluation of severe abdominal complications (Clavien–Dindo grade IIIa or above), endocrine and exocrine function. Results Of 123 patients randomized, 58 underwent PJ and 65 had PG. The incidence of pancreatic fistula was significantly higher following PJ than for PG (20 of 58 versus 10 of 65 respectively; P = 0·014), as was the severity of pancreatic fistula (grade A: 2 versus 5 per cent; grade B–C: 33 versus 11 per cent; P = 0·006). The hospital readmission rate for complications was significantly lower after PG (6 versus 24 per cent; P = 0·005), weight loss was lower (P = 0·025) and exocrine function better (P = 0·022). Conclusion The rate and severity of pancreatic fistula was significantly lower with this PG technique compared with that following PJ. Registration number: ISRCTN58328599 (http://www.controlled-trials.com).

Objectives This study aimed to compare primary surgical versus nonsurgical treatment in a series of patients with infected pancreatic necrosis (IPN) and to investigate whether the success of nonsurgical approach is related to a less severe disease. Methods Thirty-nine consecutive patients with IPN have been included and further subdivided into two groups: primary surgical (n = 21) versus nonsurgical (n = 18). Outcome measures were the differences in mortality, morbidity, and pancreatic function. Comorbidity, organ failure, and other severity indexes were compared between the two groups. Results Mortality occurred in 16.7% of cases in the nonsurgical group versus 42.9% in the surgical group. In the primary nonsurgical group, seven were operated on due to failure of initial conservative treatment. In this latter group, mortality was 28.6% and was performed significantly later than in the primary surgical group. The group of primary surgical treatment was associated with a significant higher rate of multiple organ failure (MOF) at IPN diagnosis, new onset or worsening of organ failure, and MOF and nosocomial infection after surgery. Conclusions Initial nonsurgical approach in IPN is associated with better results both in cases which respond to this treatment as well as in those who, failing this conservative approach, have to be operated on after a delayed period. Primary surgically treated patients had a more severe disease at the time of IPN.

Chronic pancreatitis (CP) is a relatively uncommon, complex and heterogeneous disease. The absence of a gold standard applicable to the initial phases of CP makes its early diagnosis difficult. Some of its complications, particularly chronic pain, can be difficult to manage. There is much variability in the diagnosis and treatment of CP and its complications amongst centers and professionals. The Spanish Pancreatic Club has developed a consensus on the management of CP. Two coordinators chose a multi-disciplinary panel of 24 experts on this disease. A list of questions was drafted, and two experts reviewed each question. Then, a draft was produced and shared with the entire panel of experts and discussed in a face-to-face meeting. This first part of the consensus addresses the diagnosis of CP and its complications. Copyright (C) 2012, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved.

Aims To evaluate postoperative morbidity and mortality, pancreatic function and long-term survival in patients with surgically treated pancreatic or periampullar tumours. Patients and methods Cohort study including 160 patients consecutively operated on: 80 pancreaticoduodenectomies (PD), 30 distal pancreatectomies (DP), 7 total pancreatectomies, 4 central pancreatic resections, and 3 ampullectomies. The tumour was not resected in 36 patients. Pancreatic function was evaluated by oral glucose tolerance test, faecal fat excretion, and elastase. Results Resectability rate was 77.5%. In resected patients (n = 124), 38.7% had complications with a pancreatic fistula rate of 6.4% and a mortality rate of 4%. In PD, endocrine function worsened in 41% and 58.6% had steatorrhoea; these figures in DP were 53.6% and 21.7% respectively. In the 36 non-resected patients, postoperative morbidity was 27.7% and mortality 8.3%. Two and 5-year survival rates in resected patients with pancreatic cancer were 42% and 9% respectively; in malignant ampulloma 71% and 53%; in mucinous adenocarcinomas 83% and 33%; in duodenal adenocarcinoma 100% and 75%; and in distal cholangiocarcinoma 50% and 50%. Conclusions Morbidity associated with resective pancreatic surgery is still high, but perioperative mortality is low. Endocrine and exocrine disturbances are very common depending on the type of resection. Despite the associated morbidity and functional disorders, surgery provides long-term survival in selected cases.

The rate of choledocholithiasis at the time of elective surgery after mild acute biliary pancreatitis is still unclear because it decreases rapidly after the onset. The aims of this study are as follows: (1) To investigate whether the incidence of choledocholithiasis in mild biliary pancreatitis is higher than in patients with symptomatic cholelithiasis. (2) To evaluate the usefulness of intraoperative cholangiography in the diagnosis of unsuspected choledocholithiasis in mild pancreatitis. Prospective study including 130 patients undergoing laparoscopic surgery and classified into two groups: mild biliary pancreatitis (n = 44) and symptomatic cholelithiasis (n = 86). Choledocholithiasis was evaluated by endoscopic cholangiopancreatography, magnetic resonance, and intraoperative cholangiography. Preoperatively, choledocholithiasis was identified in five patients with symptomatic cholelithiasis and two with biliary pancreatitis (5.81 vs 4.54%; p = 0.472). In 117 cases (90%), intraoperative cholangiography was successfully performed, identifying unsuspected choledocholithiasis in five patients of the colelithiasis group and in three in the group of pancreatitis (5.81 vs 6.81%; p = 0.492). The total number of patients with choledocholithiasis in the whole series was 15 (11.5%); 11.6% in colelithiasis group vs 11.4% in biliary pancreatitis group; p = 0.605. The rate of choledocholithiasis was not significantly different between the groups of patients with mild acute biliary pancreatitis and symptomatic cholelithiasis. Intraoperative cholangiography identified unsuspected choledocholithiasis in 6.81% of patients with mild acute biliary pancreatitis.

Chronic pancreatitis (CP) is a complex disease with a wide spectrum of clinical manifestations ranging from asymptomatic disease to disabling forms or serious complications. The management of CP frequently differs among geographical areas and even among centers. These differences are due to the scarcity of high-quality studies and clinical practice guidelines that focus on the diagnosis and treatment of this disease. The aim of the Spanish Pancreatic Club was to create evidence-based recommendations for the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts in this disease. These experts were selected on the basis of their clinical and research experience in CP. A list of questions was drawn up and each question was then reviewed by two panelists. These questions were then used to produce a draft, which was discussed in a face-to-face meeting with all the participants. Levels of evidence were based on the classification of the Oxford Centre for Evidence-Based Medicine. In the second part of the consensus process, recommendations were established for the management of pain, pseudocysts, biliary and duodenal stenosis, pancreatic fistula and ascites, left portal hypertension, diabetes mellitus, exocrine pancreatic insufficiency, and nutritional support in CP.

Chronic pancreatitis (CP) is a relatively uncommon, complex and highly heterogeneous disease. There is no clear pattern applicable to the initial stages of CP, which hampers its early diagnosis. Some of the complications of CP, especially chronic pain, can be difficult to manage. There is wide variation in the diagnosis and treatment of CP and its complications among centers and health professionals. The Spanish Pancreatic Club has developed a consensus document on the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts in this disease. A list of questions was drawn up. Each question was reviewed by two experts. These questions were then used to produce a draft, which was discussed in a face-to-face meeting with all the participants. The first part of the consensus document focusses on the diagnosis of CP and its complications.

AIM: To study the possible association between chronic pancreatitis (CP) and liver cirrhosis (LC) of alcoholic etiology, after excluding any other causes. METHODS: One hundred and forty consecutive alcoholic patients were subdivided into three groups: CP (n = 53), LC (n = 57), and asymptomatic alcoholic (n = 30). Clinical, biochemical and morphological characteristics, Child-Pugh index, indocyanine green test, and fecal pancreatic elastase-1 test were assessed. RESULTS: In patients with cirrhosis, major clinical manifestations of CP such as pancreatic pain and steatorrhea, as well as imaging alterations of CP such as calcifications, duct dilation and pseudocysts were absent; insulin-dependent diabetes was present in 5.3% of cases, and elastase-1 test was altered in only 7%, and severely altered in none. In patients with CP, clinical characteristics of cirrhosis such as ascites, encephalopathy and gastrointestinal hemorrhage were present in one case, Child-Pugh grade > A in 5.7%, and altered indocyanine green test in 1.9% cases. In asymptomatic alcoholism, there was only a non-coincident alteration of elastase-1 test and indocyanine test in 14.8% and 10%, respectively, but other characteristics of cirrhosis or CP were absent. An inverse correlation (r = -0.746) between elastase-1 test and indocyanine test was found in alcoholic patients. CONCLUSION: There is a scarce coincidence in clinical and morphological alterations among patients with CP or LC of alcoholic etiology, but an inverse correlation between pancreatic and liver function tests. These findings support that these alcoholic diseases evolve in a different manner and have different etiopathogenesis.

Autoimmune pancreatitis is a recently characterized disease that still constitutes a diagnostic challenge, especially regarding differential diagnosis from neoplasia. Long-term outcome is poorly known. We herein report a case of a patient with autoimmune pancreatitis and 14 years of follow-up, and show its clinical, biochemical, and morphological characteristics. A 54-year-old female presented with obstructive jaundice and abdominal tenderness, as well as a mass at the pancreatic head on a CT scan, suggestive of pancreatic neoplasia. Surgery showed an increase of the whole pancreas, malignancy was intraoperatively ruled out, and a cholecystectomy and choledochoduodenostomy were carried out. The diagnosis was chronic pancreatitis. Over the following years different autoimmune complications developed, including asthma, salivary gland swelling, and sclerosing cholangitis, as well as recurrent episodes of jaundice, and exocrine and endocrine pancreatic failure. The development of these complications combined with the demonstration of high serum levels of IgG4 and carbonic anhydrase II led to a re-evaluation of the initial histology of the pancreas, leading to a final diagnosis of autoimmune pancreatitis: IgG4+ lymphoplasmacytic infiltrates, fibrosis, and obliterative phlebitis. New complications developed during the last few years: retroperitoneal fibrosis with portal hypertension, esophageal varices, and splenomegaly.

Background: Increased serum antibodies against carbonic anhydrase II (CA-II Ab) or IgG4 levels have been reported in cases of autoimmune chronic pancreatitis (ACP). Aim: To assess the relevance of serum CA-II Ab and IgG4 levels for the diagnosis of ACP in idiopathic CP (ICP) versus alcoholic CP and Sjogren’s syndrome (SS). Subjects: This was a multicentre study involving 227 subjects divided into four groups: ICP (n = 54), normal controls (n = 54, paired by age and sex with ICP patients), alcoholic CP (n = 86), and SS (n = 33). Methods: CA-II Ab was measured by ELISA and confirmed by western blotting. A score of easy clinical use with major clinical, morphological, and biochemical parameters for the diagnosis of ACP was applied. Results: The percentage of patients with increased serum CA-II Ab was higher in the ICP group (28%) than in controls (1.9%) and in patients with alcoholic CP (10.5%), but lower than in patients with SS (64%). The proportion with elevated IgG4 levels was higher in the ICP group (15%) compared with controls (1.9%) and SS (0%) but not significantly different from alcoholic CP (8%). Most ICP patients (7/8) with high IgG4 levels exhibited increased CA-II Ab and a compatible ACP score. A definitive diagnosis of ACP by histological analysis was associated with other autoimmune disorders, an increase in both serum IgG4 and CA-II Ab levels, and IgG4 positive plasma cells. Conclusions: The increase in serum IgG4 levels was strongly associated with elevated CA-II Ab levels, manifestations compatible with ACP, and lymphoplasmacytic infiltration when surgical specimens were available.

This article is available from: http://www.biomedcentral.com/1471-230X/4/1, [Background] Xanthine oxidoreductase has been proposed to play a role in the development of local and systemic effects of acute pancreatitis. Under physiologic conditions, the enzyme exists mainly as xanthine dehydrogenase (XDH) but can be converted by proteolytic cleavage to its superoxide-generating form xanthine oxidase (XOD). In addition to its intracellular location XDH/XOD is also associated to the polysaccharide chains of proteoglycans on the external endothelial cell membrane. In the early stages of acute pancreatitis, this enzyme seems to be arising from its mobilization from the gastrointestinal endothelial cell surface. Taking into account the ability of α-amylase to hydrolyze the internal α-1,4 linkages of polysaccharides, we wanted to elucidate the involvement of α-amylase in XDH/XOD mobilization from the gastrointestinal endothelial cell surface and the relevance of the ascitic fluid (AF) as the source of α-amylase in experimental acute pancreatitis., [Methods] Acute pancreatitis was induced in male Wistar rats by intraductal administration of 5% sodium taurocholate. In another experimental group 3000 U/Kg α-amylase was i.v. administered. The concentrations of XDH, XOD and α- amylase in plasma and AF and myeloperoxidase (MPO) in lung have been evaluated. In additional experiments, the effect of peritoneal lavage and the absorption of α-amylase present in the AF by an isolated intestine have been determined., [Results] Similar increase in XDH+XOD activity in plasma was observed after induction of acute pancreatitis and after i.v. administration of α-amylase. Nevertheless, the conversion from XDH to XOD was only observed in the pancreatitis group. Lung inflammation measured as MPO activity was observed only in the pancreatitis group. In addition peritoneal lavage prevented the increase in α-amylase and XDH+XOD in plasma after induction of pancreatitis. Finally, it was observed that α-amylase is absorbed from the AF by the intestine., [Conclusions] During the early stages of acute pancreatitis, α-amylase absorbed from AF through the gastrointestinal tract could interfere with the binding of XDH/XOD attached to glycoproteins of the endothelial cells. Proteolytic enzymes convert XDH into its oxidase form promoting an increase in circulating XOD that has been reported to be one of the mechanisms involved in the triggering of the systemic inflammatory process., This work has been supported by FISss grants 01/0949 and PI020286; S.Granell and M.Genesca are recipients of IDIBAPS predoctoral grants.

OBJECTIVES To investigate the recovery of pancreatic function after severe acute biliary pancreatitis (ABP), especially the influence of necrosectomy on endocrine and exocrine functions. METHODS Prospective cohort study including 39 patients with severe ABP. According to need or no need for surgical necrosectomy, patients were further subdivided into 2 groups. Functional pancreatic evaluation was carried out 12 months after the ABP episode. Endocrine function was evaluated by an oral glucose tolerance test and exocrine function by fecal fat excretion, fecal chymotrypsin (FQ), and secretin-cerulein tests (SCT). RESULTS Most of the patients with necrosectomy had an abnormal exocrine pancreatic function, with steatorrhea in 25%. In the group without surgery, exocrine function was pathologic in only 13.3% and there were no cases of steatorrhea. Endocrine function was pathologic in 75% of patients undergoing necrosectomy versus 26.7% in the nonoperated group. In this latter group, the patients with abnormal endocrine function did not require insulin therapy, while in 33.3% of patient in the necrosectomy group insulin was necessary. CONCLUSIONS In our homogeneous series of severe ABP, necrosectomy impaired significantly pancreatic endocrine and exocrine function. On the other hand, most patients with the same origin and severity index, but without surgical debridement, maintained normal pancreatic function.

Pancreatic cancer, with a 5% 5-year survival rate, is the fourth leading cause of cancer death in Western countries. Unfortunately, only 20% of all patients benefit from surgical treatment. The need to prolong survival has prompted pathologists to develop improved protocols to evaluate pancreatic specimens and their surgical margins. Hopefully, the new protocols will provide clinicians with more powerful prognostic indicators and accurate information to guide their therapeutic decisions. Despite the availability of several guidelines for the handling and pathology reporting of duodenopancreatectomy specimens and their continual updating by expert pathologists, there is no consensus on basic issues such as surgical margins or the definition of incomplete excision (R1) of pancreatic ductal adenocarcinoma. This article reviews the problems and controversies that dealing with duodenopancreatectomy specimens pose to pathologists, the various terms used to define resection margins or infiltration, and reports. After reviewing the literature, including previous guidelines and based on our own experience, we present our protocol for the pathology handling of duodenopancreatectomy specimens.

The pancreaticoduodenectomy (PD) procedure may lead to pancreatic exocrine and endocrine insufficiency. There are several types of reconstruction for this kind of operation. Pancreaticogastrostomy (PG) was introduced to reduce the rate of postoperative pancreatic fistula. Although some randomized control trials have shown no differences regarding pancreatic leakage between PG and pancreaticojejunostomy (PJ), recently some reports reveal benefits from the PG over the PJ. Some surgeons concern about the performing of the PG and inactivation of pancreatic enzymes being in contact with the gastric juice, and the detrimental results over the exocrine pancreatic function. The pancreatic exocrine function can be measured with direct and indirect tests. Direct tests have the highest sensitivity and specificity for detection of exocrine insufficiency but require tube placement. Among the tubeless indirect tests, the van de Kamer stool fat analysis remains the standard to diagnose fat malabsorption. The patient compliance and time consuming makes it not so suitable for its clinical use. Fecal immunoreactive elastase test is employed for screening of exocrine insufficiency, is not cumbersome, and has been used to study pancreatic function after resection. We analyze the FE1 levels in our patients after the PD with two types of reconstruction, PG and PJ, and we discuss some considerations about the pancreaticointestinal drainage method after pancreaticoduodenectomy.

Multiple strictures of the small bowel are relatively rare. In many cases, a distinct cause can be defined, but some strictures are unexplainable by any specific mechanism and have been termed ’idiopathic’ small bowel strictures. We present 3 cases of multiple small bowel strictures in which the affected segments were studied with perioperative photoplethysmography, in vivo specimen angiography and pathology. Neither photoplethysmographic alterations nor structural vascular lesions were found.

s / Pancreatology 12 (2012) 502–597 538 interference of Sam68 and SRSF1 expression cause a partial recovery of drug sensitivity. Conclusions: Our results show that chronic exposure of PDAC cells to gemcitabine leads to selection of a drug-resistant subpopulation overexpressing Sam68 and SRSF1. Importantly, the depletion of these proteins leads to a partial recovery of the sensibility to gemcitabine, suggesting that they may represent suitable molecular-targets to overcome drug resistance in PDAC. Arumugam T, Ramachandran V, Fournier KF, et al. Epithelial to mesenchymal transition contributes to drug resistance in pancreatic cancer. Cancer Res. 2009 Jul Shapiro IM, Cheng AW, Flytzanis NC, et al. An EMT-driven alternative splicing program occurs in human breast cancer and modulates cellular phenotype. PLoS Genet. 2011 Ghigna C, De Toledo M, Bonomi S, et al. Pro-metastatic splicing of Ron proto-oncogene mRNA can be reversed: therapeutic potential of bifunctional oligonucleotides and indole derivatives. RNA Biol. 2010 Valacca C, Bonomi S, Buratti E, et al. Sam68 regulates EMT through alternative splicing-activated nonsense-mediated mRNA decay of the SF2/ASF proto-oncogene. J Cell Biol. 2010

Objetivos 1) Estudiar el papel de las serin/treonin protein fosfatasas en la induccion de genes pro-inflamatorios en el pancreas en la pancreatitis aguda, 2) Investigar el papel de las serin/treonin fosfatasas en el mecanismo de accion de la pentoxifilina como agente inflamatorio en la PA. Diseno Modelo de PA necrotica en ratas inducida por taurocolato sodico al 3,5%. Determinacion en pancreas de ratas de la fosforilacion de ERK y MEK1/2 (western blotting), las actividades de las serin/treonin fosfatasas PP2A, PP2B y PP2C, la induccion de genes pro-inflamatorios (RT-PCR e immunoprecipitacion de la cromatina) y el reclutamiento de factores de transcripcion e histonas acetiltransferasas/deacetilasas (immunoprecipitacion de la cromatina). Estudios en celulas acinares AR42J. Resultados Las actividades de las serin/treonin protein fosfatasas PP2A, PP2B y PP2C en la PA (1 h post-induccion) disminuyeron en un 50%, 57% y 29%, respectivamente, respecto a los controles. La perdida de la actividad PP2A esta mediada por una disminucion en los niveles de AMPc. La pentoxifilina actua inhibiendo la actividad fosfodiesterasa, impidiendo la perdida de la actividad PP2A inducida por el taurocolato in vivo e in vitro, sin afectar a las demas ser/thr fosfatasas. La pentoxifilina previene la induccion de genes de respuesta temprana (egr-1, atf-3) y tardia (inos, icam, il-6, tnf-alpha), y el reclutamiento de las histonas acetiltransferasas a sus promotores genicos, asi como el reclutamiento de factores de transcripcion (NF-kB y C/BPbeta) en en el curso de la pancreatitis. Conclusiones La perdida de actividad protein fosfatasa PP2A puede ser un elemento clave en el inicio de la cascada inflamatoria en la pancreatitis aguda. El efecto beneficioso de la pentoxifilina y presumiblemente de otros inhibidores de fosfodiesterasas en esta enfermedad estaria mediada por la prevencion de la perdida de los niveles de AMPc y de la actividad PP2A en etapas muy tempranas de la pancreatitis aguda.

Liver pseudocysts are a very rare complication in acute pancreatitis with only a few cases previously described. The lack of experience and literature on this condition leads to difficulties in the differential diagnosis and management. We report herein a case of acute pancreatitis who developed multiple intrahepatic pseudocysts. After complete imaging evaluation, the diagnosis was still unclear and the patient was operated on. The presence of liver lesions in patients with acute pancreatitis should raise the possibility of intrahepatic pseudocysts.

Disconnected pancreatic duct syndrome is a serious complication of acute pancreatitis which is defined by a complete discontinuity of the pancreatic duct, such that a viable side of the pancreas remains isolated from the gastrointestinal tract. This pancreatic disruption is infrequently observed in the clinical practice and its diagnostic and therapeutic management are controversial. We present an extreme case of disconnected pancreatic duct syndrome with complete duct disruption and pancreatic transection following acute pancreatitis, as well as the diagnostic and therapeutic processes carried out.