Cause Of Chronic Pancreatitis Research Articles

Management of Pancreatic Calculi in Chronic Pancreatitis: A Review Article.

Chronic pancreatitis is a slow, irreversible, and progressive inflammatory condition with abdominal pain, loss of parenchyma, fibrosis, and calculus formation. It also causes loss of exocrine and endocrine function. Gallstones and alcohol is the most frequent cause of chronic pancreatitis. It is also caused by other factors, including oxidative stress, fibrosis, and repeated incidence of acute pancreatitis. Chronic pancreatitis is followed by several sequelae, one of them being formation of calculi in the pancreas. The formation of calculi can occur in the main pancreatic duct, branches of the duct, and parenchyma. The cardinal sign of chronic pancreatitis is pain caused by obstruction of pancreatic ducts and its branches leading to ductal hypertension resulting in pain. The main aim of endotherapy includes pancreatic duct decompression. The management options vary based on the type and size of the calculus. The treatment of choice for small-sized pancreatic calculi is endoscopic retrograde cholangiopancreatography (ERCP) followed by sphincterotomy and extraction. The large-sized calculi need fragmentation before extraction, which is done by extracorporeal shock wave lithotripsy (ESWL). Surgery can be an option for patients having severe pancreatic calculi if endoscopic therapy fails. For diagnostic purposes, imaging plays a very important role. The treatment options remain complex if the radiological and laboratory findings overlap. Due to advancements in diagnostic imaging, treatment options have become precise and helpful. It can significantly lower the quality of life along with immediate and long-term problems that pose a serious risk to life. This review comprises the various management options available for removing calculi following chronic pancreatitis, including surgical, endoscopic, and medical therapy.

PSUN236 Previously Undiagnosed Hereditary Pancreatitis Presenting as New Onset Type 3c Diabetes Mellitus

Abstract Background Type 3c Diabetes Mellitus (DM3c) or Pancreatogenic Diabetes is defined as diabetes secondary to pancreatic disease. The most common cause of Type 3c Diabetes is chronic pancreatitis, accounting for 80% of cases.1 Hereditary pancreatitis, with mutations such as SPINK1, CFTR, CTRC, is an underdiagnosed cause of chronic pancreatitis leading to Type 3c Diabetes Mellitus.1 The typical disease course for hereditary pancreatitis is recurrent episodes of acute pancreatitis that leads to chronic pancreatitis.1 The average time between hereditary pancreatitis diagnosis and development of DM3c has been shown to be 80 +/- 24 months.1 We present a case of previously undiagnosed hereditary pancreatitis presenting as new onset Type 3c Diabetes Mellitus. Clinical Case A 33-year-old male presents with a two month history of diarrhea, epigastric pain, and weight loss. Vital signs on presentation were blood pressure 105/74, heart rate 59, BMI 13. Physical exam revealed a cachectic appearing male with epigastric tenderness. Lab-work showed blood glucose 819 mg/dL, SOsm 313 mOsm/kg, lipase 21 U/L, bicarbonate 33 mmol/L. A computed tomography (CT) of the abdomen revealed punctate pancreatic parenchymal calcifications, suggestive of chronic pancreatitis. He was admitted to general medicine for management of HHS, where he was treated with IV hydration and insulin therapy. Workup for new onset diabetes revealed a negative anti-GAD Ab <5.0 U/mL, and C peptide level 0.5 ng/mL which suggested β cell dysfunction and decreased endogenous insulin secretion. With these lab values, along with radiographic findings consistent with chronic pancreatitis, the likely driving factor for his diabetes was pancreatic disease and he was diagnosed with DM3c. Severe pancreatic disease was further shown by a reduced fecal elastase level of <50, suggesting exocrine pancreatic insufficiency. Investigating the etiology of his chronic pancreatitis, history revealed no prior episodes of acute pancreatitis or abdominal pain, and no family history of pancreatitis. Workup for common causes of pancreatitis, including alcohol use, hypertriglyceridemia, and gallstones was negative, and genetic workup was pursued. The patient was found to be heterozygous for a SPINK1 mutation, which is a known mutation in hereditary pancreatitis.1 Therefore, hereditary pancreatitis was determined to be the likely cause of his chronic pancreatitis which led to Type 3c Diabetes Mellitus. He was started on daily insulin therapy and pancreatic enzymes for his endocrine and exocrine pancreatic dysfunction respectively, with improvement in symptoms. Conclusion This is a unique case of hereditary pancreatitis presenting as new onset Type 3c Diabetes Mellitus with no prior episodes of acute pancreatitis or established diagnosis of chronic pancreatitis. References Ramalho, G. X., & Dytz, M. G. (2020). Diabetes of the exocrine pancreas related to hereditary pancreatitis, an update. Current Diabetes Reports, 20(6). Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

The transcription factor JUN is a major regulator of quiescent pancreatic stellate cell maintenance

Pancreatic stellate cell (PSC) activation is a major cause of chronic pancreatitis and pancreatic cancer, yet the mechanisms by which PSCs switch from quiescent to activated state are poorly studied. In this study, we identified JUN, a key transcription factor that maintains the quiescent state of PSCs, by integrating single-cell sequencing data from multiple pancreatic tissues and using WGCNA and SCENIC algorithms, and demonstrated that the expression and activity of JUN is a major regulator of the quiescent state of PSCs through cellular experiments and multiple pancreatic-related disease bulk RNAseq data. This study explores the main mechanism of PSC activation and provides a theoretical basis for the treatment of multiple pancreatic injury-related diseases caused by PSCs.

IDF21-0114 Comparative Study of the Clinical Profile of FCPD and T2DM patients and Assess the Link of inflammatory markers and IR

Background: In progression of type 2 diabetes mellitus, inflammation plays an extremely vital and critical role along with insulin resistance (IR) and in long term results in further worsening of complications specially in fibrocalculous pancreatic diabetic patients (FCPD). FCPD is an uncommon form of diabetes that occurs as a result of chronic calcific pancreatitis, in the absence of alcohol abuse. Diabetes in FCPD is often brittle and difficult to control and most patients require multiple doses of insulin for control of glycemia. Aim: To assess the link between bio-inflammatory markers and IR in fibrocalculous pancreatic diabetic patients. Method: It is a cross sectional observational study. hsCRP was considered for assessing bio-inflammatory factor and HOMA index for IR among 70 FCPD subjects and 100 type 2 diabetes (T2DM). FCPD was diagnosed by evidence of ductal dilation measured by ultrasonography or by presence of pancreatic calculi on abdominal X-ray and absence of alcoholism, or other known causes of chronic pancreatitis in existing T2DM subjects. Results: 59.6±4.8 years was the mean age of the FCPD group whereas 37.4±5.1 years were for T2DM groups. FCPD patients had an earlier age at onset of diabetes (36.3 ± 15.1 years vs. 46.0±10.0 years; P = 0.031). BMI (20.7±2.1 vs 25.6±3.2 kg/m2), serum total cholesterol (147±34 vs 174±41 mg/dl), triglyceride (142±43 vs 217±94 mg/dl), and LDL cholesterol levels (91±24 vs 109±36 mg/dl) were significantly lower among FCPD patients than the T2DM patients (P<0.001). 22 subjects in FCPD group and 39 subjects in T2DM group were also diagnosed with retinopathy after initial fundoscopy. Glycated hemoglobin levels (HbA1C) were significantly higher in patients with FCPD as compare to T2DM group (9.4±2.2 vs 8.5±1.2 %, p<0.001). HOMA index among the FCPD group was 4.21 ± 1.1where as it was 5.37 ± 1.8 in T2DM group with significant P value (<0.05). A statistically significant difference (p < 0.001) was observed between the FCPD and T2DM in hsCRP (3.7±1.1 vs 1.6± 0.8). Discussion: Insulin resistance as measured by HOMA IR and inflammatory markers measured by hsCRP were found to be higher in pancreatic patients to that of type 2 DM. Despite the fact that the prevalence of FCPD being low, considering its impact of the condition on the quality of life (QOL) of the patients periodic screening is required specially for T2DM patients who complains of weight loss, back pain, abdominal pain, steatorrhoea or jaundice. Longer survival of FCPD patients also mandates periodic screening for possible risk of pancreatic adenocarcinoma.

EP261: The spectrum of CFTR and PRSS1 pathogenic variants in chronic pancreatitis

Chronic pancreatitis is defined as persistent inflammation of the pancreas that is ongoing for 6 months or longer. Chronic pancreatitis often develops by early adulthood in affected individuals and can lead to permanent tissue damage and loss of pancreatic function, including both exocrine and endocrine pancreatic insufficiency. Chronic pancreatitis increases the risk for diabetes and pancreatic cancer, more so with smoking and use of alcohol. Variants in several genes have been identified to be causative for, or induce susceptibility to, chronic pancreatitis. Genetic testing for hereditary chronic pancreatitis can aid in differential diagnosis of chronic pancreatitis from other disorders which also present with pancreatitis and may inform treatment strategy. This study reports the spectrum of pathogenic variants in individuals referred for chronic pancreatitis panel testing. This study included 747 individuals who underwent chronic pancreatitis panel testing at a single clinical laboratory (PreventionGenetics) between June 15, 2018 and September 24, 2021. Clinical information was obtained from provider-completed test requisition forms. Next generation sequencing (NGS) with copy number variant (CNV) detection was performed on patient-derived DNA using the Illumina NovaSeq 6000 platform (Illumina, San Diego, CA, USA) and Sanger sequencing as necessary. Testing provided 100% coverage for the coding regions of the CASR, CFTR, CTRC, PRSS1, and SPINK1 genes plus ∼10 bases of non-coding DNA flanking each exon, as well as non-coding regions in which pathogenic variants had been identified by the clinical testing laboratory or reported elsewhere. The test also included sequencing of CFTR regions within intron 11 and intron 21, along with a complete analysis of the compound (TG)n(T)n sequence (5T/TG tract) in intron 8. Variations in the 5T/TG tract have been reported to cause congenital absence of the vas deferens, non-classic cystic fibrosis, and classic cystic fibrosis. At time of testing, the patients ranged in age from 1 week to 87 years, with a median age of 32 years. Of the patients tested, 68% were negative for variants in genes included on the panel that are likely to cause disease while 27% were found to be indeterminate, where variants were identified but the results were not diagnostic. Overall, 5% of patients were positive, with a clear molecular diagnosis identified. Pathogenic and likely pathogenic variants in CFTR and PRSS1 accounted for 90% of positive cases overall, with 42% of positive cases being attributed to CFTR-related pancreatitis (1 homozygous or 2 heterozygous causative variants identified) and 33% of positive cases attributed to PRSS1-related pancreatitis (1 heterozygous causative variant). An additional 15% of positive cases were found to have pathogenic or likely pathogenic variants in both CFTR and PRSS1 (1 heterozygous causative variant in both CFTR and PRSS1). The CFTR c.1210-34TG[12]T[5] variant (more commonly referred to as 5T/12TG) contributed to ∼21% of CFTR-related pancreatitis. Importantly, ∼72% of pathogenic and likely pathogenic variants identified in this patient cohort are approved as therapy responsive variants for FDA approved CFTR modulators. In approximately 40% of patients with PRSS1-related pancreatitis, we detected a ∼600kb copy number gain encompassing the whole PRSS1 gene, compared to an estimated 6% of patients in the literature. These data indicate that variants in CFTR are a common cause of chronic pancreatitis and highlights the clinic utility of including complete analysis of the compound (TG)n(T)n sequence (5T/TG tract) in intron 8 of CFTR in this patient cohort. Additionally, the high frequency of treatment responsive variants suggests that a molecular diagnosis in patients with chronic pancreatitis may alter treatment strategy, particularly in the context of CFTR-related pancreatitis. Furthermore, these data suggest that whole gene deletions/duplications may be more frequent that previously thought in this patient cohort and that complex copy number variants in the PRSS1 gene may escape detection by other NGS testing strategies.

Into the Duct: An Unusual Source of Bacteremia

A 52-year-old male presented to the hospital with a 3-day history of high-grade fever (over 39.0°C), arthralgia, and headache. He was diagnosed with acute pancreatitis for the first time at 28 years of age. Since then, he has been admitted several times due to chronic pancreatitis. The cause of chronic pancreatitis had been assumed to be alcohol consumption. Three months prior, he received an endoscopic ultrasound-fine needle aspiration to evaluate a mass in the pancreatic head, which yielded no evidence of malignancy.

Pathogenesis of chronic pancreatitis

Long-term alcohol consumption and gene mutations are the most important causes of chronic pancreatitis. In addition to mutations in acinar genes, such as digestive enzymes and their inhibitors, defects in genes that primarily or exclusively affect the duct cells have also been described in recent years. Genetic changes are found not only in patients with apositive family history (hereditary pancreatitis) but also in so-called idiopathic and, to alesser extent, in alcoholic chronic pancreatitis. The coming years will likely show that there are very complex interactions between environmental influences and numerous genetic factors.

Low Bone Mineral Density and Risk for Osteoporotic Fractures in Patients with Chronic Pancreatitis.

Introduction: Chronic pancreatitis (CP) can lead to malnutrition, an established risk factor for low bone mineral density (BMD) and fractures. This study aims to determine the prevalence of low BMD, assess fracture incidence and explore risk factors for fractures in patients with CP. Patients and methods: We performed a retrospective analysis of all patients treated for CP at Karolinska University Hospital between January 1999 and December 2020. Electronic medical records were retrieved to assess demographic, laboratory and clinical data. Patients subjected to dual-energy X-ray absorptiometry (DXA) were categorised as either low BMD or normal BMD. We investigated whether the rate of fractures, defined by chart review, differed between these groups using Cox regression, adjusting the model for age, sex and body mass index (BMI). Additional within-group survival analysis was conducted to identify potential risk factors. Results: DXA was performed in 23% of patients with definite CP. Some 118 patients were included in the final analysis. Low BMD was present in 63 (53.4%) patients. Mean age at CP diagnosis in the total cohort was 53.1 years and was significantly lower in patients with normal BMD than in patients with low BMD (45.5 vs. 59.8, p < 0.001). Significant differences were observed in smoking status and disease aetiology, i.e., a higher proportion of patients with low BMD were current or former smokers, with nicotine or alcohol being a more common cause of CP (p < 0.05). Total follow-up time was 898 person-years. Fractures were found in 33 (28.0%) patients: in 5 of 55 patients (16.7%) with normal DXA and in 28 of 63 patients (44.4%) with low BMD (adjusted hazard ratio = 3.4, 95% confidence interval (CI) = 1.2–9.6). Patients with at least 3 months of consecutive pancreatic enzyme replacement therapy (PERT) or vitamin D treatment had a longer median time to fracture after CP diagnosis. Conclusion: DXA was only performed in 23% of patients with definite CP in this study, indicating a low adherence to current European guidelines. A low BMD was found in 53.4% of patients with CP, and 44% of the patients with a low BMD experienced a fracture during follow-up. Moreover, the fracture rate in patients with low BMD increased compared to those with normal BMD.

Scale and Scope of Gene-Alcohol Interactions in Chronic Pancreatitis: A Systematic Review.

Background: Excessive alcohol consumption has long been known to be the primary cause of chronic pancreatitis (CP) but genetic risk factors have been increasingly identified over the past 25 years. The scale and scope of gene-alcohol interactions in CP nevertheless remain unclear. Methods: All studies that had obtained genetic variant data concurrently on alcoholic CP (ACP) patients, non-ACP (NACP) patients and normal controls were collated. Employing normal controls as a common baseline, paired ORACP and ORNACP (odds ratios associated with ACP and NACP, respectively) values were calculated and used to assess gene-alcohol interactions. Results: Thirteen variants involving PRSS1, SPINK1, CTRC, CLDN2, CPA1, CEL and CTRB1-CTRB2, and varying from very rare to common, were collated. Seven variants had an ORACP > ORNACP, which was regarded as an immediate indicator of gene-alcohol interactions in CP. Variants with an ORACP < ORNACP were also found to interact with alcohol consumption by virtue of their impact on age at first pancreatitis symptoms in ACP. Conclusions: This study revealed evidence for extensive gene-alcohol interactions in CP. Our findings lend support to the hypothesis that alcohol affects the expression of genetically determined CP and highlight a predominant role of weak-effect variants in the development of ACP.

Inhibitory Smads suppress pancreatic stellate cell activation through negative feedback in chronic pancreatitis.

BackgroundActivation of pancreatic stellate cells (PSCs) is a key cause of chronic pancreatitis (CP), while inhibition of transforming growth factor-β (TGF-β) signaling renders PSCs inactive. Inhibitory Smads (I-Smads) impede TGF-β intracellular signaling and may provide a way to alleviate CP. Thus, we aimed to investigate the molecular mechanism of I-Smads in CP animals and freshly-isolated PSCs.MethodsSixteen male C57BL/6 mice were randomly divided into two groups; a control group (treated with saline) and a CP group (treated with caerulein) for 6 weeks. Masson’s staining was performed to identify fibrosis, and immunohistochemistry (IHC) was performed to measure the levels of Smad6 between the two groups. An improved method derived from internal digestion was used to isolate PSCs from male Sprague Dawley rats. Quantitative real-time polymerase chain reaction (qRT-PCR) and immunofluorescence staining were used to measure the messenger ribonucleic acid (mRNA) and protein levels of alpha-smooth muscle actin (α-SMA). Plasmids of I-Smads or SB431542 were transfected into freshly-isolated PSCs, and relative mRNA levels of marker genes were quantified by qRT-PCR. The two-tailed Student’s t-test was performed to assess significance.ResultsThe Smad6 protein level was significantly higher in the pancreas tissue of CP mice compared to the control group. A large number of PSCs were isolated from rat pancreas using an improved isolating method and were confirmed by quiescent and active PSC markers including cluster differentiation antigen 133 (CD133), perilipin 2 (Plin2), α-SMA, Desmin, and collagen 1 (Col1). The mRNA levels of both Smad6 and Smad7 were down-regulated during freshly-isolated PSC activation. Over-expression of both Smad6 and Smad7 in freshly-isolated PSC reduced the mRNA level of α-SMA, glial fibrillary acidic protein (GFAP), Desmin, Col1, Col3, and fibronectin 1 (Fn1) significantly. SB431542 reduced the mRNA level of α-SMA, Col1, Col3, and Fn1 significantly in freshly-isolated PSCs.ConclusionsThis study demonstrated that CP promoted the expression of I-Smads, which suppressed the activation of freshly-isolated PSCs via a negative feedback loop.

OR26-04 Immediate Post-Operative Insulin Requirements May Predict Metabolic Outcome After Total Pancreatectomy and Islet Autologous Cell Transplant (TPIAT)

Immediate Post-Operative Insulin Requirements may Predict Metabolic Outcome after Total Pancreatectomy and Islet Autologous Cell Transplant (TPIAT) Introduction: Chronic pancreatitis (CP) is a progressive disease that leads to eventual loss of endocrine and exocrine function. Patients with CP experience abdominal pain, which in some instances can be refractory to medical and endoscopic intervention. Total pancreatectomy and islet auto transplantation (TPIAT) is a treatment option however predicting postoperative metabolic outcomes remains elusive. In this single-center retrospective study, we report pre-TPIAT characteristics, beta cell function indices, islet yield as well as post-TPIAT glucose management data to further understand their relationship.Methods:A total of 13 TPIAT subjects were included who underwent beta cell function assessment via intravenous glucose tolerance tests and oral mixed meal tolerance tests. Islet yield, glucose level and insulin requirement for 72 hours postoperatively were collected. In addition, their glucose control and insulin requirements at 3, 6 and 12-month post TPIAT were analyzed.Results:The median age was 45 years with median duration of CP for 5 years. The main cause of CP was idiopathic. All 13 subjects had normal baseline fasting glucose levels. Median islet yield was 4882 IEq/kg (interquartile range 3412 to 8987). Median post-operative total insulin requirement on day 3 was 0.43 units/kg. Pre-TPIAT baseline glucose, insulin or c-peptide level did not have a significant correlation with the islet yield. Similarly, there was no correlation between islet yield and insulin requirement at 72-hour post operatively. However, there was an inverse correlation between the absolute islet yield (IEq) and insulin requirement at 6 months and 12 months following post-TPIAT. Further analysis of the relationship between 72-hour post-op insulin requirement and insulin requirement at discharge, 3, 6 and 12 month showed a positive correlation. Despite the new finding of inverse correlation of islet yield with long-term insulin requirement, this study was not able to detect a correlation between the preoperative parameters to postoperative short-term or long-term outcome as noted in other studies.Conclusion: The 72-hour postoperative insulin requirement is a helpful postoperative predictor of patients needing long term insulin management following TPIAT. This observation may identify a high risk group of patients in need of more intensive diabetes education and treatment prior to hospital discharge.

Case Report: Autoimmune Pancreatitis: About a Case in Hepato-Gastroenterology Department of Mother-Child Hospital in Bamako/Mali

Autoimmune pancreatitis is a distinct form of chronic pancreatitis. It is a chronic pancreatitis distinct from alcohol, genetic or idiopathic impairment and involves possible autoimmune mechanisms. The diagnosis of autoimmune pancreatitis is based on a body of biological, histological and radiological arguments. Also called sclerosing lymphoplasmacytic pancreatitis, it is one of the causes of chronic pancreatitis. The risk factor for the onset of cancer that it represents and its sensitivity to corticosteroids make it a pathology requiring special management. We report a case of autoimmune pancreatitis in a 35-year-old patient.

3009 Importance of Prompt Diagnosing and Treatment of Type 1 Autoimmune Pancreatitis

INTRODUCTION: Type 1 Autoimmune Pancreatitis (AIP) is a rare cause of chronic pancreatitis that accounts for only 2% of chronic pancreatitis cases. Mainly presenting in males between ages of 50-70. This is IgG4 related disease. It commonly presents with abdominal pain, jaundice, and weight loss. AIP is primarily diagnosed clinically and later confirmed through radiological and serological studies. Because pancreatic cancer presents similarly but differentiates in treatment, it is important to distinguish between the two. CASE DESCRIPTION/METHODS: A 72-year-old male with a PMH of chronic pancreatitis presented for evaluation of loss of appetite, fatigue and 100 lb weight loss over the course of 7 weeks. He also admitted to two weeks of chills and diaphoresis, and denied abdominal pain, diarrhea or constipation. On admission, there was no jaundice present and vitals were unremarkable, except for a temperature of 102 F. Patient's labs were within normal limits, except for sodium 129, ESR 85, total bilirubin 1.3, AST 101, ALT 79, and ALP 364. CT showed the pancreas heterogeneous, an ill-defined mass, consistent with pancreatic adenocarcinoma. Furthermore it showed hepatomegaly with numerous low-density lesions consistent with hepatic metastases. Biopsy of the pancreatic mass displayed a storiform fibrosis pattern with an elevated IgG4 of 3.8 g/L, suggesting Type 1 AIP. Liver biopsy was negative for malignant cells. Patient was diagnosed with AIP and was discharged on a steroid regimen. DISCUSSION: Type 1 AIP is defined as a fibro-inflammatory process that often includes elevated IgG4 levels. Imaging can also reveal irregular narrowing of the pancreatic duct with diffuse or focal enlargement of the pancreas. It is important to distinguish between AIP and pancreatic cancer due to the different treatments and prognosis. A study found AIP to account for 27% of Whipple resections performed for suspected pancreatic adenocarcinoma. AIP has a benign clinical course and is highly responsive to steroids. An elevated IgG4 together with imaging studies are the most sensitive and specific finding; an IgG4 value of &gt;2.8 g/L distinguishes AIP from other inflammatory or malignant conditions. Finally, the prompt diagnosis of AIP is important for appropriate follow up. Studies have demonstrated an increased risk of developing cancer of the stomach, prostate, colon and bile duct post diagnosis of AIP. A retrospective study of 108 patients with AIP, 18 cancers were found in 15 patients in the median follow-up period of 3.3 years.

Генетические особенности и варианты течения наследственного панкреатита у детей

Chronic pancreatitis is a polyetiological disease characterized by progressive structural changes of the pancreas with the development of its exo- and endocrine insufficiency. In childhood, possible causes of chronic pancreatitis may be obstruction of the ducts of pancreas due to gallstone disease, chronic cholecystitis with biliary sludge, anomalies of the excretory ducts; obesity and hyperlipidemia; injuries of the abdomen and infectious lesions of the gland. In recent years, due to better diagnostics, new probable variants of chronic pancreatitis have been found: autoimmune and hereditary. According to reviewing data, more than 70% of children with idiopathic chronic pancreatitis have genetic mutations of SFTR, PRSS1 and SPINK1 genes, both single and combined. This leads to disturbance of the balance of activation and inactivation of trypsinogen in the pancreatic tissue. Severe mutations can be an independent cause of chronic pancreatitis, mild mutations manifest after environmental impact. The study included: a) family cases of pancreatitis (16 families, 37 patients); b) patients with idiopathic pancreatitis, i. e., with the presence of acute recurrent or chronic pancreatitis of unknown etiology and the absence of similar diseases among relatives (n = 21). An analysis of 19 frequent mutations in 5 known genes (PRSS1, SPINK1, CTRC, CFTR, CPA1) associated with the development of NP was carried out. Results: mutations were detected in 11 of 58 patients (19%), and in two of 190 healthy donors (2%); p <0.0001. The cause of the development of pancreatitis was identified in members of 5 of 16 (31%) families, and only in 1 of 27 (4%) patients with an idiopathic form of the disease.

A case of late recognition of the malignant cause of chronic pancreatitis

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Pancreatic Ductal Deletion of Hnf1b Disrupts Exocrine Homeostasis, Leads to Pancreatitis, and Facilitates Tumorigenesis.

Background & AimsThe exocrine pancreas consists of acinar cells that produce digestive enzymes transported to the intestine through a branched ductal epithelium. Chronic pancreatitis is characterized by progressive inflammation, fibrosis, and loss of acinar tissue. These changes of the exocrine tissue are risk factors for pancreatic cancer. The cause of chronic pancreatitis cannot be identified in one quarter of patients. Here, we investigated how duct dysfunction could contribute to pancreatitis development.MethodsThe transcription factor Hnf1b, first expressed in pancreatic progenitors, is strictly restricted to ductal cells from late embryogenesis. We previously showed that Hnf1b is crucial for pancreas morphogenesis but its postnatal role still remains unelucidated. To investigate the role of pancreatic ducts in exocrine homeostasis, we inactivated the Hnf1b gene in vivo in mouse ductal cells.ResultsWe uncovered that postnatal Hnf1b inactivation in pancreatic ducts leads to chronic pancreatitis in adults. Hnf1bΔduct mutants show dilatation of ducts, loss of acinar cells, acinar-to-ductal metaplasia, and lipomatosis. We deciphered the early events involved, with down-regulation of cystic disease–associated genes, loss of primary cilia, up-regulation of signaling pathways, especially the Yap pathway, which is involved in acinar-to-ductal metaplasia. Remarkably, Hnf1bΔduct mutants developed pancreatic intraepithelial neoplasia and promote pancreatic intraepithelial neoplasia progression in concert with KRAS. We further showed that adult Hnf1b inactivation in pancreatic ducts is associated with impaired regeneration after injury, with persistent metaplasia and initiation of neoplasia.ConclusionsLoss of Hnf1b in ductal cells leads to chronic pancreatitis and neoplasia. This study shows that Hnf1b deficiency may contribute to diseases of the exocrine pancreas and gains further insight into the etiology of pancreatitis and tumorigenesis.

A Clinical Analysis of Surgical treatment for the Chronic Pancreatitis

Introduction: In general, Frey procedure is adopted for chronic pancreatitis (CP) with lesions in the head of the pancreas from the viewpoint of preservation of pancreatic function. However, depending on the condition, cases that select pancreatectomy may also be admitted. We examined cases of CP surgery in our hospital. Method: From 2009 to 2017, 21 patients were underwent surgery for CP in our department, and their clinical features were examined. Result: The cause of CP was alcoholic in 16 cases and idiopathic in 5 cases. The surgical procedure was selected as below, Frey operation: 13 cases, Partington operation: 1 case, PD: 4 cases, DP: 3 cases. Biliary jejunum anastomosis was added to 3 cases of Frey surgery. Pancreatic ductal jejunal anastomosis was added in 1 case of DP. PD was selected for two patients with a possibility of pancreatic cancer, and for two cases who formed pseudocysts in the head of the pancreas. Surgical-related death was not admitted. The pancreatic fistula of grade B or more was seen in 5 cases. 1 case who underwent Partington operation, pancreatitis at the head of the pancreas repeated, and portal vein thrombosis occurred concurrently. The pain remission rate of surgical treatment for CP was 95.2%. Preoperative diabetes mellitus was observed in 6 cases, but no cases newly developed diabetes after surgery were observed. Conclusion: The outcome of the surgical treatment for CP was good and acceptable. Basically, Frey operation was selected for CP of the head of the pancreas. But performing pancreatectomy sometimes improve the outcome according to the situation. So, it is necessary to select appropriate surgical procedure for CP.

IgG4 Autoimmune Pancreatitis: A G-Force Worth Fighting

Introduction: Autoimmune Pancreatitis (AIP) is a rare but increasingly more recognized cause of chronic pancreatitis. AIP can be divided into Type 1 and Type 2, which are characterized by high amounts of IgG4 Plasma Cells and Granulocytic Epithelial Lesions, respectively. Until recently, most AIP was diagnosed in patients who underwent Pancreaticoduodenectomy due to concern for pancreatic cancer. With the advent of Endoscopic Ultrasound (EUS) and Fine Needle Biopsy (FNB), a less invasive realm for diagnosis and management is now utilized. Here we present a case of a patient with acute pancreatitis and a mysterious pancreatic mass.1304_A.tif Figure 1: CT scan image of tail of pancreas lesion1304_B.tif Figure 2: EUS image of tail of pancreas lesion1304_C.tif Figure 3: Representative H&E sections highlight a dense inflammatory infiltrate composed of lymphocytes, plasma cells and other mixed components, as well as fibrosis within the pancreatic parenchyma; C) IgG+ plasma cells, representative immunohistochemistry section; D) IgG4+ plasma cells, representative immunohistochemistry section.Case report: A 49 year old female presented with abdominal pain and a lipase of 1227. Though the patient had symptoms consistent with acute pancreatitis, she did not have any major risk factors nor familial history. CT Imaging revealed a 4 cm tail of pancreas solid mass. To rule out malignancy, an EUS was performed which showed 3.1 x 3.2 cm hypoechoic and heterogenous mass with poorly formed borders. FNB was successfully done with histopathology revealing storiform fibrosis without granulation, up to 25 IgG4 plasma cells in a high power field, and an IgG4/IgG ratio greater than 40%. The diagnosis of Type 1 AIP was made with a high serum IgG4 level of 109. Ultimately, a corticosteroid taper was initiated which brought resolution of the patient's symptomology. Discussion: Criteria for diagnosis of AIP include 5 distinct entities recognized by the mnemonic HISORt (histology, imaging, serology, organ involvement, and response to therapy). Imaging findings typically show a sausage shape of the pancreas, multifocal strictures, and a positive duct penetrating sign. Tissue histology for Type 1 AIP reveals sheets of plasma cells, storiform fibrosis, and positive IgG4 immunostaining of plasma cells. Upon diagnosis, immunoglobulin deposition within the biliary tree and hepatic parenchyma, as well as multi-organ manifestations of the more broadly termed “IgG4 related diseases” should be taken into clinical consideration. A trucut biopsy was initially indicated since fine needle aspiration (FNA) diagnostic yield was 43%. With the second generation FNB needle the use of trucut biopsy is not needed. First line therapy involves a course of corticosteroids that is typically tapered based on organ responsiveness. More recent case series include depletion of the B cell line with Rituximab for patient's refractory to steroids.

A Rare Case of Acute Cholangitis in a Young Male with Tropical Chronic Pancreatitis-Induced Pancreatic Adenocarcinoma with Metastasis to the Liver

Tropical chronic pancreatitis (TCP) is a rare and poorly understood variant of chronic pancreatitis. It is typically diagnosed in young, nonalcoholic patients in tropical regions such as southern Asia, often presenting with abdominal pain, and leading to several complications, including diabetes, malnutrition, and pancreatic adenocarcinoma. Though the link between chronic pancreatitis and cancer is established, the risk for malignancy is highest in those with rare causes of chronic pancreatitis. We present a case of TCP-induced pancreatic adenocarcinoma complicated by acute cholangitis. A 34 year-old Bangladeshi male with TCP complicated by diabetes and stage IV pancreatic adenocarcinoma with liver metastasis, s/p whipple procedure, and 3 cycles of adjuvant Gemcitabine and Abraxane presented with acute worsening of chronic abdominal pain. Labs were remarkable for elevated liver enzymes and a marked increase in CA 19-9. CT Abdomen/Pelvis revealed progression of metastatic disease in the liver and upper abdomen, including the peritoneum and anterior abdominal wall. His pain persisted despite EUS-guided celiac plexus block, but became acutely worse on hospital day 15 when he became febrile, jaundiced, and with blood cultures growing E. Coli, Klebsiella, and Aeromonas. Due to concern for acute cholangitis secondary to stenosis of hepaticojejunostomy, he was taken for ERCP. The biliary system was not successfully identified, so he then underwent IR-guided placement of a biliary drain via percutaneous transhepatic cholangiography, which showed central biliary stenosis and severe bilateral ductal dilation. He was subsequently placed in hospice due to his poor prognosis. The etiology of TCP is multifactorial, but also associated with a mutation of the SPINK1 gene, which causes parenchymal damage by lowering the threshold for trypsin activation. Characteristic radiographic findings include a dilated pancreatic duct with large intra-ductal calculi, pancreatic calcifications, and pancreatic atrophy. Data suggests that only 5% of patients with a 20-year history of chronic pancreatitis develop cancer, but 17% of patients with TCP develop malignancy, which is significantly higher than the near 0% risk of malignancy in those with chronic alcoholic pancreatitis. TCP is a rare disease that potentiates many long-term complications that can significantly increase mortality in an otherwise young and healthy population.1273_A.tif Figure 1: Marked dilation of pancreatic duct measuring up to 18 mm (blue arrow) that terminates at the pancreatic head due to a large calcification (red arrow).1273_B.tif Figure 2: Fine needle aspiration of mass at pancreatic head (blue arrow) and dilated CBD measuring up to 13mm (red arrow).1273_C.tif Figure 3: Multiple hepatic metastatic lesions (blue arrows) and invasion of the pancreatic head mass into the anterior abdominal wall (red arrow).

Predicting the efficacy of surgery for pain relief in patients with alcoholic chronic pancreatitis

BackgroundRecurrent pain is the most disabling complication in patients with chronic pancreatitis. Pancreatic surgery is currently considered as last-resort therapeutic option. The aims of this study were to assess pancreatic surgery performance for chronic pain in patients with alcoholic chronic pancreatitis and to determine factors predictive of therapeutic response. MethodsAll patients with chronic pancreatitis who underwent pancreatic surgery for chronic pain were included and divided into 2 groups according to the cause of chronic pancreatitis: alcoholic and any other chronic pancreatitis causes as the control group. Alcohol, tobacco, and painkiller intake, quality of life data 6 months and 1 year after surgery, and morphological and pathological features were analyzed. ResultsFifty patients were included in the alcoholic chronic pancreatitis group and 16 patients in the control group. Smoking cessation before pancreatic surgery was achieved in 40% of the alcoholic chronic pancreatitis group compared with 73% of the control group (P = .005). Histological analysis revealed a higher prevalence of hypertrophic nerves and perineural inflammation in the alcoholic chronic pancreatitis group than in the control group (P = .03 and P = .04 respectively). In multivariate analysis, in the alcoholic chronic pancreatitis group, factors predictive of 6-month narcotic use cessation were surgery performed within a maximum of 2 years after chronic pancreatitis diagnosis (odds ratio = 4.228 [1.04–17.17]) and postoperative smoking cessation (odds ratio = 3.561 [1.021–12.41]); at 1 year, only smoking cessation was predictive of narcotic use cessation (odds ratio = 11.33 [2.677–47.98]). ConclusionIn patients with alcoholic chronic pancreatitis undergoing surgery for chronic pain, narcotic use cessation and improved quality of life depend on early surgery and complete smoking cessation.