Successful Management of Hemosuccus Pancreaticus due to Pancreatic Adenocarcinoma by Chemoradiotherapy.

Management of hemosuccus pancreaticus (HP) due to pancreatic adenocarcinoma is problematic. This is the first report of the successful management of HP caused by pancreatic adenocarcinoma by chemoradiotherapy, which is a treatment option for cases with a high surgical risk that are not suitable for interventional radiology. In the present case, bloody pancreatic juice was detected in the main pancreatic duct, and anemia worsened without repeated blood transfusions. The patient ultimately underwent chemoradiotherapy comprising radiation of 3 Gy in 15 fractions concomitant with systemic chemotherapy of S-1. After the treatments, the anemia improved, and the patient was discharged on day 45.

Extrinsic compression of pancreactic duct by intragastric balloon treatment and its potential to cause acute pancreatitis: two case reports and clinical discussion.

We describe two cases of increased pancreatic enzyme levels after intragastric balloon (IGB) placement possibly related to extrinsic pancreatic duct compression, followed by a short review of the literature. Case 1 is the first, to our knowledge, of a patient with asymptomatic increase of pancreatic enzymes due to pancreatic duct compression, with unknown clinical significance. We hypothesize that this finding maybe can be relatively common in IGB users and almost certainly an important risk factor for the development of acute pancreatitis (AP). On the other hand, case 2 reports an AP that occurred one day after IGB placement, presented with nausea and vomiting, making AP a differential diagnosis of initial IGB intolerance.

Mechanism of pancreatic juice reflux in pancreaticobiliary maljunction: A fluid dynamics model experiment.

BACKGROUND: Pancreatic juice reflux to the common bile duct and gallbladder is observed in the pancreaticobiliary maljunction (PBM), and various pathological conditions occur in the biliary tract. However, the mechanism of pancreatic juice reflux has not been discussed yet. This study aimed to investigate the mechanism of this phenomenon from the perspective of the fluid dynamics theory. METHODS: A fluid dynamics model of PBM without biliary dilatation having gallbladder function and of the pressure of sphincter of Oddi was developed. Water (as bile juice and pancreatic juice) was flowed to these models with a flow rate similar to that in humans. Pancreatic and bile juice flow and bile duct pressure were observed in three phases of gallbladder function. Moreover, the same experiment was performed in the PBM without biliary dilatation model without gallbladder. RESULTS: Pancreatic juice reflux could be observed when the gallbladder was passively expanded with the pressure in the bile duct lower than that in the sphincter of Oddi. However, pancreatic juice reflux was not observed in the model without gallbladder. CONCLUSIONS: Gallbladder function may be strongly involved in pancreatic juice reflux in PBM without biliary dilatation. Cholecystectomy may be able to stop the reflux of pancreatic juice.

Risk factors of post-ERCP pancreatitis in high-risk patients despite prevention with prophylactic pancreatic stents.

Objectives: To analyze risk factors of post-ERCP pancreatitis (PEP) in high risk patients in whom prophylactic pancreatic stents (PPSs) were intended to use to prevent endoscopic retrograde cholangiography (ERCP)-related complications.Patients and methods: Three hundred and seventeen high-risk patients for developing PEP were considered for preventive pancreatic stent placement in our endoscopy unit over 5 years. 5 Fr, 3-5 cm long PPSs were used. All data were collected in a predefined database. Development of PEP despite PPS placement was analyzed.Results: PEP occurred in 29 of 288 successfully stented patients (10.07%; 24 mild, four moderate, one severe). PPS was protective against all risks factors except for sphincter of Oddi dysfunction (SOD). PPS related complication rate was 2.78% (n = 8). Unsuccessful stenting occurred in 29 patients (9.15%), PEP developed in 41.38% (n = 12; seven mild, four moderate, one severe). Those patients who had more patient related risk factors were more likely to develop PEP despite preventive measures with PPS. On the contrary, PPS placement was less successful in patients who had more procedure related risk factors.Conclusions: PPS is protective against all risks factors of PEP except for SOD in high-risk patients. More vulnerable patients who have more patient-related risk factors are more likely to develop PEP despite PPS is used, while more complex procedures predispose to unsuccessful PPS placement in patients with more procedure-related risk factors. PPS insertion in high-risk patients is effective and safe preventive method and the procedure related complication rate is reasonably low.

Hemosuccus pancreaticus: rara asociación entre pancreatitis aguda, alcoholismo y sesiones vasculares en la circulación esplácnica / Hemosuccus Pancreaticus: an unusual association of acute pancreatitis, alcoholism and vascular abnormalities of the splanchnic circulation

La pancreatitis aguda o crónica puede resultar en lesiones del conducto pancreático, además, la corrosión por el jugo pancreático puede provocar la ruptura de la pared vascular periférica, lo que conduce a hemosuccus pancreático (HP) definido como el sangrado del conducto pancreático a través de la ampolla de Vater. El sangrado suele ser intermitente, repetitivo y, a menudo, no lo suficientemente grave, como para causar inestabilidad hemodinámica. La mayoría de los pacientes tiene antecedentes de enfermedades pancreáticas originales y cuando esto no se cumple, debe incluirse en el diagnóstico diferencial para alcohólicos crónicos con hemorragia digestiva alta intermitente. Presentamos una forma clínica atípica en un paciente masculino de 55 años de edad, con antecedentes de HTA, alcoholismo y aneurisma de la aorta abdominal, quien consultó por dolor tipo cólico en abdomen superior, náuseas y vómitos; luego se asoció disminución del estado de conciencia, alternando con episodios de agitación psicomotriz y primo convulsión generalizada. Una vez ingresado, sucedieron varios episodios de melena. La tomografía abdominal mostró aumento de tamaño y densidad (unidades hounsfield de 58-61) en cabeza y cuerpo del páncreas, por lo que se realizó una angiografía abdominal con protocolo de páncreas y se evidenció doble lesión aneurismática de la arteria esplénica y la arteria gástrica. Falleció en el postoperatorio(AU)

Acute or chronic pancreatitis can result in lesions of the pancreatic duct; in addition, corrosion by the pancreatic juice can cause the rupture of the peripheral vascular wall, which leads to pancreatic hemosuccus defined as bleeding from the pancreatic duct through the Vater ampulla. Bleeding is often intermittent, repetitive, and often not severe enough to cause hemodynamic instability. Most of the cases have a history of strictly pancreatic original diseases, when this is not the case, the PH should be included in the differential diagnosis for chronic alcoholics with intermittent upper gastrointestinal bleeding, We report here an atypical presentation in a 55-year-old male patient with a history of hypertension, alcoholism and an abdominal aortic aneurysm. He consulted for colicky abdominal pain in the upper abdomen, nausea and vomiting; subsequently he presented decreased consciousness, alternating with episodes of psychomotor agitation and generalized seizures. Once hospitalized he had several bouts of melena. The abdominal tomography showed an increase in the size and density (hounsfield units of 58-61) of the head and body of the pancreas. An abdominal angiography with a pancreas protocol was performed, which evidenced a double aneurismal lesion of the splenic and gastric arteries. The patient died after surgery(AU)

Activation of the Nuclear Factor-kappa B Signaling Pathway Damages the Epithelial Barrier in the Human Pancreatic Ductal Adenocarcinoma Cell Line HPAF-II.

OBJECTIVES: Injury of the pancreatic duct epithelial barrier plays a critical role in the development of acute pancreatitis. The activity of the nuclear factor-kappa B (NF-κB) pathway is involved in the disruption of the pancreatic duct epithelial barrier. This study investigated how NF-κB impacts the dysfunction of the pancreatic duct epithelial barrier. METHODS: A human pancreatic ductal adenocarcinoma cell line was treated with tumor necrosis factor-alpha (TNF-α) and pyrrolidine dithiocarbamate. The expression levels of p65 and p-p65 were detected to evaluate NF-κB activity. Tricellulin (TRIC) expression levels were measured to assess the change in tight junction (TJ)-related proteins. The expression and localization of myosin light chain kinase (MLCK) were investigated. The structure of TJs and monolayer permeability were also examined. RESULTS: NF-κB was activated by TNF-α and suppressed by pyrrolidine dithiocarbamate. Activation of NF-κB upregulated the expression levels of TRIC and MLCK. Broadened TJs were observed after NF-κB was activated. Lower monolayer permeability was observed when NF-κB was suppressed. CONCLUSIONS: Activation of the NF-κB pathway induced by TNF-α leads to increased TRIC and MLCK expression, resulting in broadened TJs and high permeability, which contribute to damage to the pancreatic duct epithelial barrier.

Long-Term Functional Outcome After Pancreatoduodenectomy for Periampullary Carcinoma With Morphological Correlation.

OBJECTIVE: The aim of the study was to evaluate the long-term functional outcome (exocrine and endocrine) and morphological changes in remnant pancreas after pancreatoduodenectomy and its clinical impact. METHODS: Periampullary carcinoma patients with minimum follow-up of 2 years and without recurrence were included (N = 102). Exocrine insufficiency includes clinical steatorrhea and fecal elastase-1 (FE-1) levels; endocrine insufficiency, glucose levels and glycated hemoglobin; and morphological changes, main pancreatic duct (MPD) diameter and thickness of remnant pancreas. RESULTS: The mean (standard deviation) follow-up period was 59 (26) months. Of the 102 patients, 81 (80%) had severely deficient FE-1 (0-100 µg/g). The preoperative MPD was significantly more and thickness of remnant pancreas was significantly less in patients with severely deficient FE-1. Overall, 15.6% (16/102) developed steatorrhea and improved on enzyme replacement therapy. The presence of MPD stricture (P = 0.008) and weight loss (P = 0.001) were significantly associated with steatorrhea. New-onset diabetes was seen in 17% (15/90) patients, of whom 3 of 5 developed it after 4 years (range, 4-7 years). The blood glucose was controlled on oral hypoglycemics in 2 (10/15) of 3 patients. CONCLUSIONS: The assessment by FE-1 indicates loss of exocrine function in more than 90%, whereas only 1 of 6 developed steatorrhea and new-onset diabetes. Morphological changes especially MPD stricture affect the functional status of remnant pancreas.

Meandering Main Pancreatic Duct in Association with Choledochal Cysts and Acute Pancreatitis in Pediatrics.

Meandering main pancreatic duct (MMPD) is an uncommon anomaly of the main pancreatic duct characterized by an abnormal curvature at the pancreatic head region. This variant can be diagnosed on imaging, particularly magnetic resonance cholangiopancreatography (MRCP). Although its clinical significance remains debatable, recent research suggests an association with recurrent acute pancreatitis. To our knowledge, no pediatric cases of acute or recurrent acute pancreatitis have been attributed to the presence of MMPD. In this article, we report on two patients. The first case is of a 15-year-old girl with MMPD discovered on investigation of idiopathic acute pancreatitis. The second case is of a 5-year-old boy who presented with his second episode of acute pancreatitis. In this patient, MRCP imaging revealed MMPD and type IVA choledochal cyst. With appropriate care, both patients experienced clinical improvement with resolution of abdominal pain. This article highlights MMPD as a distinct entity that should be considered in pediatric patients with recurrent attacks of acute pancreatitis. This report also describes the first association of MMPD with choledochal cysts. [Pediatr Ann. 2019;48(10):e412-e416.].

Pancreas Divisum in Pediatric Acute Recurrent and Chronic Pancreatitis: Report From INSPPIRE.

INTRODUCTION: The significance of pancreas divisum (PD) as a risk factor for pancreatitis is controversial. We analyzed the characteristics of children with PD associated with acute recurrent or chronic pancreatitis to better understand its impact. PATIENTS AND METHODS: We compared children with or without PD in the well-phenotyped INSPPIRE (INternational Study group of Pediatric Pancreatitis: In search for a cuRE) cohort. Differences were analyzed using 2-sample t test or Wilcoxon rank sum test for continuous variables, Pearson χ or Fisher exact test for categorical variables. RESULTS: PD was found in 52 of 359 (14.5%) subjects, a higher prevalence than the general population (∼7%). Females more commonly had PD (71% vs. 55%; P=0.02). Children with PD did not have a higher incidence of mutations in SPINK1, CFTR, CTRC compared with children with no PD. Children with PD were less likely to have PRSS1 mutations (10% vs. 34%; P<0.01) or a family history of pancreatitis (P<0.05), and more likely to have hypertriglyceridemia (11% vs. 3%; P=0.03). Children with PD underwent significantly more endoscopic procedures and pancreatic sphincterotomy. Patients with PD had fewer attacks of acute pancreatitis (P=0.03) and were less likely to develop exocrine pancreatic insufficiency (P=0.01). Therapeutic endoscopic retrograde cholangiopancreatography was considered most helpful if pancreatic duct was impacted with stones (83% helpful). CONCLUSIONS: PD is likely a risk factor for acute recurrent pancreatitis and chronic pancreatitis in children that appears to act independently of genetic risk factors. Patients with PD and stones obstructing the pancreatic duct benefit most from therapeutic endoscopic retrograde cholangiopancreatography.

Ductal Cell Reprogramming to Insulin-Producing Beta-Like Cells as a Potential Beta Cell Replacement Source for Chronic Pancreatitis.

Islet cell auto-transplantation is a novel strategy for maintaining blood glucose levels and improving the quality of life in patients with chronic pancreatitis (CP). Despite the many recent advances associated with this therapy, obtaining a good yield of islet infusate still remains a pressing challenge. Reprogramming technology, by making use of the pancreatic exocrine compartment, can open the possibility of generating novel insulin-producing cells. Several lineage-tracing studies present evidence that exocrine cells undergo dedifferentiation into a progenitor-like state from which they can be manipulated to form insulin-producing cells. This review will present an overview of recent reports that demonstrate the potential of utilizing pancreatic ductal cells (PDCs) for reprogramming into insulin- producing cells, focusing on the recent advances and the conflicting views. A large pool of ductal cells is released along with islets during the human islet isolation process, but these cells are separated from the pure islets during the purification process. By identifying and improving existing ductal cell culture methods and developing a better understanding of mechanisms by which these cells can be manipulated to form hormone-producing islet-like cells, PDCs could prove to be a strong clinical tool in providing an alternative beta cell source, thus helping CP patients maintain their long-term glucose levels.

Predictive Factors of Pancreatic Fistula After Pancreaticoduodenectomy and External Validation of Predictive Scores.

BACKGROUND/AIM: The Fistula Risk Score (FRS), as other risk scores, is a validated model predicting the development of a clinically relevant post-operative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy (PD). We evaluated risk factors related with CR-POPF and correlated four predictive scores with the likelihood of developing CR-POPF in our cohort. PATIENTS AND METHODS: The records of 107 patients who underwent PD from 2007 to 2015 were obtained from a prospectively maintained database and reviewed. CR-POPFs were categorized by the International Study Group of Pancreatic Fistula (ISGPF) standards. Firstly, a univariate and multivariate analysis of risk factors related to CR-PPOPF was performed, and then the data were correlated with FRS, Wellner's, Robert's and Yamamoto's scores. RESULTS: In total, 30 patients developed a CR-POPF. On multivariate analysis, abdominal thickness (OR=1.02, p=0.010), Wirsung's duct diameter (OR=0.57, p=0.029), pancreatic consistency (OR=3.18, p=0.011) and histological diagnosis of the lesion (OR=1.65, p=0.012) represented independent predictive factors of CR-POPF. FRS (R2=0.596, p=0.001), Wellner's score (R2=0.285, p=0.005) and Roberts' score (R2=0.385, p=0.002) correlated with the likelihood of developing CR-POPF. CONCLUSION: Abdominal thickness, Wirsung's duct diameter, pancreatic consistency and histological diagnosis were independent predictive factors of CR-POPF. Predictive scores reflected the likelihood of CR-POPF, FRS being the score with the highest predictive value.

Adverse Events and Reinterventions Following Pancreatic Endoscopic Sphincterotomy.

OBJECTIVES: Pancreatic endoscopic sphincterotomy (PES) is an independent risk factor for short- and long-term adverse events (AEs) of endoscopic retrograde cholangiopancreatography. We sought to measure PES-specific AEs and trends in the use of PES. METHODS: This was a retrospective cohort of consecutive patients who underwent first-time PES between June 2008 and June 2015. Indications for PES were dichotomized: (1) structural pathology (chronic pancreatitis and local complications of acute pancreatitis) and (2) suspected sphincter pathology (idiopathic recurrent acute pancreatitis and sphincter of Oddi dysfunction). Rates of AEs and pancreatic orifice reinterventions were measured, with reintervention rates limited to those having a minimum of 12-month follow-up. RESULTS: Of 567 patients, 198 (34.9%) underwent PES for structural and 369 (65.1%) for suspected sphincter pathology. Rates of post-endoscopic retrograde cholangiopancreatography pancreatitis and unplanned hospitalization were high when PES was originally performed for suspected sphincter pathology (12.6% and 14.6%, respectively). The overall reintervention rate was 28.9% and significantly greater for sphincter (41.7%) compared with structural pathology (13.5%, P = 0.005). CONCLUSIONS: The likelihood of reintervention after PES is high, particularly when the primary indication is suspected sphincter pathology such as idiopathic recurrent acute pancreatitis. Further prospective studies are needed to clarify if and when this maneuver confers significant benefit to patients.

Evaluation of pancreatic exocrine insufficiency by cine-dynamic MRCP using spatially selective inversion-recovery (IR) pulse: Correlation with severity of chronic pancreatitis based on morphological changes of pancreatic duct.

PURPOSE: To evaluate the correlation between the pancreatic exocrine insufficiency estimated by cine-dynamic MRCP using spatially selective IR pulse and the severity stages (modified Cambridge classification) based on morphological changes of the pancreatic duct in patients with suspected chronic pancreatitis. MATERIALS AND METHODS: Thirty-nine patients with suspected chronic pancreatitis underwent cine-dynamic MRCP with a spatially selective IR pulse. The secretion grading score (5-point scale) based on the moving distance of pancreatic juice inflow on cine-dynamic MRCP was assessed, and compared with the stage of the severity of chronic pancreatitis based on morphological changes of pancreatic duct. RESULT: The stage of the severity of chronic pancreatitis based on morphological changes had significant negative correlations with the secretion grade (r=-0.698, P<0.001). The secretion grading score of stage 4 was significantly lower than stage 1-3 (P<0.001, P=0.002, P=0.025, respectively). In all 19 patients in stage 4, the secretion grading score was <0.70. The secretion grading score of stage 1 was significantly higher than stage 2 and 4 (P=0.019, P<0.001, respectively). In stage 2, the secretion grading score was <0.70 in 8 (89%) of 9 patients showing pancreatic exocrine insufficiency. Conversely, in stage 3, the secretion grading score was >0.70 in 2 (33%) of 6 patients showing normal pancreatic exocrine function. CONCLUSION: It should be noted that the degree of morphological changes of pancreatic duct does not necessarily reflect the severity of pancreatic exocrine insufficiency at cine-dynamic MRCP in stage 2-3 chronic pancreatitis.

Pancreaticobiliary maljunction and congenital biliary dilatation.

Pancreaticobiliary maljunction is a congenital malformation in which the pancreatic and bile ducts join outside the duodenal wall, usually forming a long common channel. Because the action of the sphincter of Oddi does not regulate the function of the pancreaticobiliary junction in patients with pancreaticobiliary maljunction, two-way regurgitation occurs. Reflux of pancreatic juice into the biliary tract is associated with a high incidence of biliary cancer. Biliary carcinogenesis in patients with pancreaticobiliary maljunction is thought to follow the hyperplasia, dysplasia, then carcinoma sequence due to chronic inflammation caused by pancreatobiliary reflux. Pancreaticobiliary maljunction is diagnosed when an abnormally long common channel is evident on imaging studies. Congenital biliary dilatation involves both local dilatation of the extrahepatic bile duct, including the common bile duct, and pancreaticobiliary maljunction. Extrahepatic bile duct resection is the standard surgery for congenital biliary dilatation. However, complete excision of the intrapancreatic bile duct and removal of stenoses of the hepatic ducts are necessary to prevent serious complications after surgery.

Are Internal or External Pancreatic Duct Stents the Preferred Choice for Patients Undergoing Pancreaticoduodenectomy? A Meta-Analysis.

The technique of pancreatic duct stenting during pancreatic anastomosis can markedly reduce the incidence of postoperative pancreatic fistula (PF) after pancreaticoduodenectomy (PD). The method of drainage includes using either an external or an internal stent; the meta-analysis result shows us that there were no differences in the rates of postoperative complications between PD using internal stents and PD using external stents; internal stents may be more favorable during postoperative management of drainage tube. What is more, internal stents could reduce the digestive fluid loss and benefit the digestive function.

Diagnosis of Chronic Pancreatitis Incorporating Endosonographic Features, Demographics, and Behavioral Risk.

OBJECTIVES: Diagnosing chronic pancreatitis remains challenging. Endoscopic ultrasound (EUS) is utilized to evaluate pancreatic disease. Abnormal pancreas function test is considered the "nonhistologic" criterion standard for chronic pancreatitis. We derived a prediction model for abnormal endoscopic pancreatic function test (ePFT) by enriching EUS findings with patient demographic and pancreatitis behavioral risk characteristics. METHODS: Demographics, behavioral risk characteristics, EUS findings, and peak bicarbonate results were collected from patients evaluated for pancreatic disease. Abnormal ePFT was defined as peak bicarbonate of less than 75 mEq/L. We fit a logistic regression model and converted it to a risk score system. The risk score was validated using 1000 bootstrap simulations. RESULTS: A total of 176 patients were included; 61% were female with median age of 48 years (interquartile range, 38-57 years). Abnormal ePFT rate was 39.2% (69/176). Four variables formulated the risk score: alcohol or smoking status, number of parenchymal abnormalities, number of ductal abnormalities, and calcifications. Abnormal ePFT occurred in 10.7% with scores 4 or less versus 92.0% scoring 20 or greater. The model C-statistic was 0.78 (95% confidence interval, 0.71-0.85). CONCLUSIONS: Number of EUS pancreatic duct and parenchymal abnormalities, presence of calcification, and smoking/alcohol status were predictive of abnormal ePFT. This simple model has good discrimination for ePFT results.