Chronic Pancreatitis Patient Research Articles

SEC16A Variants Predispose to Chronic Pancreatitis by Impairing ER-to-Golgi Transport and Inducing ER Stress.

Chronic pancreatitis (CP) is a complex disease with genetic and environmental factors at play. Through trio exome sequencing, a de novo SEC16A frameshift variant in a Chinese teenage CP patient is identified. Subsequent targeted next-generation sequencing of the SEC16A gene in 1,061 Chinese CP patients and 1,196 controls reveals a higher allele frequency of rare nonsynonymous SEC16A variants in patients (4.90%vs 2.93%; odds ratio [OR], 1.71; 95% confidence interval [CI], 1.26-2.33). Similar enrichments are noted in a French cohort (OR, 2.74; 95% CI, 1.67-4.50) and in a biobank meta-analysis (OR, 1.16; 95% CI, 1.04-1.31). Notably, Chinese CP patients with SEC16A variants exhibit a median onset age 5 years earlier than those without (40.0vs 45.0; p=0.012). Functional studies using three CRISPR/Cas9-edited HEK293T cell lines show that loss-of-function SEC16A variants disrupt coat protein complex II (COPII) formation, impede secretory protein vesicles trafficking, and induce endoplasmic reticulum (ER) stress due to protein overload. Sec16a+/- mice, which demonstrate impaired zymogen secretion and exacerbated ER stress compared to Sec16a+/+, are further generated. In cerulein-stimulated pancreatitis models, Sec16a+/- mice display heightened pancreatic inflammation and fibrosis compared to wild-type mice. These findings implicate a novel pathogenic mechanism predisposing to CP.

Activin A signaling stimulates neutrophil activation and macrophage migration in pancreatitis

Acute Pancreatitis (AP) is associated with high mortality and current treatment options are limited to supportive care. We found that blockade of activin A (activin) in mice improves outcomes in two murine models of AP. To test the hypothesis that activin is produced early in response to pancreatitis and is maintained throughout disease progression to stimulate immune cells, we first performed digital spatial profiling (DSP) of human chronic pancreatitis (CP) patient tissue. Then, transwell migration assays using RAW264.7 mouse macrophages and qPCR analysis of “neutrophil-like” HL-60 cells were used for functional correlation. Immunofluorescence and western blots on cerulein-induced pancreatitis samples from pancreatic acinar cell-specific Kras knock-in (Ptf1aCreER™; LSL-KrasG12D) and functional WT Ptf1aCreER™ mouse lines mimicking AP and CP to allow for in vivo confirmation. Our data suggest activin promotes neutrophil and macrophage activation both in situ and in vitro, while pancreatic activin production is increased as early as 1 h in response to pancreatitis and is maintained throughout CP in vivo. Taken together, activin is produced early in response to pancreatitis and is maintained throughout disease progression to promote neutrophil and macrophage activation.

Clinical characterization of the silent chronic pancreatitis patient: a single-center retrospective cohort study.

Silent chronic pancreatitis (SCP) is a poorly understood subtype of chronic pancreatitis (CP) in which individuals describe little to no abdominal pain. The risk factors for SCP are unclear, and it is unknown whether there are differences in the clinical outcomes of SCP and painful CP. We set out to investigate the clinical features of SCP and the risk factors associated with this condition. This was a retrospective cohort study using data from the Penn State Milton S. Hershey Medical Center from 2019-2022. Two patient groups, the SCP cohort (23 patients) and the painful CP cohort (94 patients), were identified from consecutive clinics. Descriptive statistics and bivariate and logistic regression analyses (including variables with a P-value <0.1 on bivariate analysis) were performed to characterize the study cohort and to evaluate for independent associations with SCP. SCP was independently associated with older age (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.01-1.11; P=0.03) and male sex (OR 5.38, 95%CI 1.38-20.96; P=0.02), and inversely associated with current opioid use (OR 0.18, 95%CI 0.03-0.96; P=0.04). There was no association between SCP and current pain medication or diabetes mellitus. Our study adds to the growing body of literature describing SCP as a condition associated with older age and male sex, and inversely associated with opioid use. We found no greater association of diabetes with SCP. Future larger longitudinal studies are needed to gain a better understanding of SCP.

Endoscopic Ultrasound-Guided Celiac Plexus Block Can Be a Useful Procedure for Pain Relief in Chronic Pancreatitis When Used Selectively

Abstract Background and Objectives: Endoscopic ultrasound (EUS)-guided celiac plexus block (CPB) for pain relief in chronic pancreatitis (CP) has wide variation in results as reported in the literature. The objective was to find out the efficacy of EUS-CPB in painful CP from our region where phenotype of CP is different from West and to find out factors favoring response to EUS-CPB. Methods and Results: Patients with known CP who underwent EUS-CPB were assessed for response to CPB. Response to EUS-CPB was recorded as more than 50% reduction in visual analogue scale (VAS) score for pain severity at 1 week, 4 weeks, 12 weeks and 24 weeks after procedure. Factors between responders and nonresponders were analyzed. Among 29 patients who underwent EUS-CPB during the study period, response was seen in 72.4% patients after the procedure. The mean time to response to EUS-CPB was 1.22 (± 0.43) days. Mean duration of response was 8 months (± 4.73). Short duration of painful CP (≤2 years) was seen in 15 patients (51.72%) and long duration (&gt;2 years) was seen in 14 (48.27%). Among responders (21/29), those patients who had short duration of disease had significantly lower median VAS score at 12 weeks, (1 versus 3, p-value= 0.026) and at 24 weeks, (1.5 versus 2.5, p-value= 0.049), as compared to those with longer duration of disease. Overall, 83.3% males responded as compared to 54.54% females (p = 0.04). Significant proportion of subjects who responded either stopped or used analgesics occasionally (p &lt; 0.0001). There was no statistically significant difference in response to EUS-CPB with respect to age, prior history of endoscopic retrograde cholangiopancreatography (ERCP), etiology of CP, prior history of surgery, or whether only EUS-CBP was done (p &gt; 0.05 for all). Conclusion: EUS-CPB can be effective when used in select group of painful CP patient who are not immediate candidates for surgery especially in early course of disease. It can be offered to patients with persistent pain despite optimum medical therapy. When effective, it can reduce need for analgesic medication at least in short to medium term.

Giant solitary pancreatic stone in a chronic pancreatitis patient

Giant solitary pancreatic stone in a chronic pancreatitis patient

A rare PRSS1 p.S127C mutation is associated with chronic pancreatitis and causes misfolding-induced ER-stress

Background/Objectives: Sequence variants in several genes have been identified as being associated with an increased inherited risk to develop chronic pancreatitis (CP). In a genetic survey of a CP patient we identified in the PRSS1gene a new c.380C > G sequence variation, giving rise to a non-synonymous p.S127C mutation. Functional studies were performed to analyze the associated pathophysiology of the variant. MethodsFollowing generation of an expression vector for the new PRSS1 variant we compared its expression, secretion and catalytic activity with already known PRSS1 risk variants in HEK 293T cells. The intracellular protein accumulation and induction of endoplasmic reticulum (ER)-stress was analyzed. ResultsPrediction tool analysis indicated a probably deleterious effect of the p.S127C variant on protein function which was confirmed by detection of a secretion defect in HEK293T cells leading to intracellular protein accumulation. While protein misfolding was associated with reduced trypsin activity, the increased expression of BIP and presence of spliced XBP1 indicated that the p.S127C variant induces ER stress and activates the UPR signaling pathway. ConclusionsThe disease mechanism of the PRSS1 p.S127C variant involves defective protein secretion and the induction of ER-stress due to accumulation of presumably misfolded trypsinogen within the ER. The new variant should be considered disease-causing with an incomplete penetrance. Our results confirm that in addition to dysregulated trypsin-activity or reduced fluid secretion, ER-stress induction is an important trigger for acinar cell damage and the development of recurrent or chronic pancreatic inflammation.

Physical activity for chronic pancreatitis: a systematic review.

Chronic pancreatitis (CP) is a progressive inflammatory disorder of the pancreas. Sarcopenia is a degenerative loss of skeletal muscle mass, quality, and strength and is commonly associated with chronic pancreatitis. Regular physical activity and adequate functional fitness have been found to ameliorate the risk and effects of sarcopenia in other chronic diseases. The objective of this systematic review was to collate all the published evidence which has examined any type of physical activity as an intervention in the chronic pancreatitis patient population. This systematic review was conducted in accordance with the PRISMA guidelines. The search strategy was designed by the medical librarian (DM) for Embase and then modified for the other search platforms. Two of the researchers (BM) and (AM) then performed the literature search using the databases Embase, Medline, CINAHL, and Web of Science. An electronic identified a total of 571 references imported to Covidence as 420 when the duplicates (151) were removed. 420 titles were screened and 390 were removed as not relevant from their titles. 30 full text papers were selected and from these, only one full text paper was deemed suitable for inclusion. There is currently insufficient evidence to advise physical activity in the chronic pancreatitis population. However, given the evidence to support physical activity in many other chronic diseases this review highlights the need for urgent investigation of physical activity as an intervention on this specific patient population.

Pancreatic fistula presenting with bloody ascites and acute peritonitis in a chronic pancreatitis patient: a case report

Pancreatic fistula presenting with bloody ascites and acute peritonitis in a chronic pancreatitis patient: a case report

A study of the clinical profile of acute pancreatitis and it’s correlation with severity indices

Background: Acute pancreatitis is an inflammatory process with possible peripancreatic tissue and multi organ involvement inducing multi organ dysfunction syndrome (MODS) with an increased mortality rate. Acute pancreatitis may vary in severity, from mild self-limiting pancreatic inflammation to pancreatic necrosis with life-threatening sequelae. Severity of acute pancreatitis is linked to the presence of systemic organ dysfunctions and/or necrotizing pancreatitis. Methods: This is prospective study of 100 patients diagnosed as having acute pancreatitis and after obtaining informed written consent of patient. Patients inclusive are all the patients with diagnosis of acute pancreatitis (consecutive 100 patients) admitted in tertiary care hospital. Patients with chronic pancreatitis and pancreatic malignancy and Patient not willing to participate in the study excluded from the study. Results and Conclusions: In present study it is concluded that Gall stone is the commonest cause, epigastric pain is the commonest mode of presentation, while Pleural effusion is most common complication of acute pancreatitis. Two or more severity indices should be used for determining severity, prediction of early complications and mortality associated with acute pancreatitis

Progression of parenchymal and ductal findings in patients with chronic pancreatitis: A 4-year follow-up MRI study

PurposeKnowledge of the underlying mechanisms behind progression of chronic pancreatitis (CP) is needed to identify targets for new mechanism-based treatments. There is an urgent need for imaging biomarkers that can detect early morphological and functional pancreatic damage in order to initiate intervention and reduce the progression of CP at an early stage. The aim of our study was to assess and explore the potential role of structural magnetic resonance imaging (MRI) biomarkers for characterisation of disease progression in a CP patient cohort over a 4-year period. MethodsThis longitudinal MRI study included twenty-five patients with definitive CP. Assessments of morphological imaging parameters at baseline and after 4 years included pancreatic gland volume, apparent diffusion coefficient (ADC) values, fat signal fraction (FSF) and main pancreatic duct (MPD) diameter. Patients were classified according to the modified Cambridge classification. ResultsCP patients developed significantly reduced pancreatic gland volume, which decreased from mean 50.3 ± 19.6 ml at baseline to 43.5 ± 20.8 ml at follow-up (P < 0.001), decreased ADC values, meaning a higher degree of fibrosis (P < 0.001), increased FSF, meaning more fat infiltration (P < 0.001) and higher Cambridge classification scores (P = 0.033). The MPD diameter in the pancreatic head, body and tail did not change significantly over time (all P > 0.05). Only few, but no clear and systematic, associations were found between the progressions of the individual MRI measures. ConclusionsMorphological progression in patients with established CP seems to be primarily parenchymal-related. The different parenchymal changes were mostly unrelated and probably reflect diverse pathophysiological processes.

Serum amphiregulin level and pancreatic adenocarcinoma relation in patients with chronic pancreatitis

Background /Aims : We aimed in our study to determine serum amphiregulin level, which is an indicator of a malignancy, and to foresee pancreatic carcinoma in chronic pancreatitis.Materials and Methods: 42 patients who applied to Department of Gastroenterology and were diagnosed with chronic pancreatitis and 43 healthy patients as the control group were enrolled in the study. Serum amphiregulin levels were studied with an Amphiregulin Human ELISA Kit ab99975 (Abcam, Cambridge, UK) by ELISA(Enzyme-Linked Immunosorbent Assay) method. Results: Patients with chronic pancreatitis compared to healthy control group (p : 0.007) and the group complicated with pseudocyst among chronic pancreatitis patient group, serum amphiregulin level (p : 0.006) and Ca 19-9 (p : 0.03) level are high. We also found that the relationship between the long diameter of the pseudocyst and serum amphiregulin level is statistically significant (p : 0.01) in the complicated chronic pancreatitis group. Conclusion: Patients with chronic pancreatitis and the group complicated with pseudocyst among chronic pancreatitis patient group must be monitored more closely in terms of pancreatic cancer since serum amphiregulin level and Ca 19-9 level are high and the relationship between the long diameter of the pseudocyst and serum amphiregulin level is statistically significant in such patient groups.

Proteomic analyses of ECM during pancreatic ductal adenocarcinoma progression reveal different contributions by tumor and stromal cells

Pancreatic ductal adenocarcinoma (PDAC) has prominent extracellular matrix (ECM) that compromises treatments yet cannot be nonselectively disrupted without adverse consequences. ECM of PDAC, despite the recognition of its importance, has not been comprehensively studied in patients. In this study, we used quantitative mass spectrometry (MS)-based proteomics to characterize ECM proteins in normal pancreas and pancreatic intraepithelial neoplasia (PanIN)- and PDAC-bearing pancreas from both human patients and mouse genetic models, as well as chronic pancreatitis patient samples. We describe detailed changes in both abundance and complexity of matrisome proteins in the course of PDAC progression. We reveal an early up-regulated group of matrisome proteins in PanIN, which are further up-regulated in PDAC, and we uncover notable similarities in matrix changes between pancreatitis and PDAC. We further assigned cellular origins to matrisome proteins by performing MS on multiple lines of human-to-mouse xenograft tumors. We found that, although stromal cells produce over 90% of the ECM mass, elevated levels of ECM proteins derived from the tumor cells, but not those produced exclusively by stromal cells, tend to correlate with poor patient survival. Furthermore, distinct pathways were implicated in regulating expression of matrisome proteins in cancer cells and stromal cells. We suggest that, rather than global suppression of ECM production, more precise ECM manipulations, such as targeting tumor-promoting ECM proteins and their regulators in cancer cells, could be more effective therapeutically.

Evaluation clinical and biochemical characteristics of patients with chronic pancreatitis

Objective: Chronic pancreatitis is a chronic, progressive, irreversible benign inflammatory process, resulting in structural changes with disorders of functional exocrine and endocrine parenchyma by a fibrotic and inflammatory tissue. Based on clinical characteristics and morphology to diagnose chronic pancreatitis. This study was assessing the clinical, biochemical characteristics of chronic pancreatitis patients; and evaluating the relationship between grade chronic pancreatitis and clinical, biochemical characteristics. Subjects and methods: A cross-sectional study was conducted on 51 patients with chronic pancreatitis diagnosed based on Rosemont Criteria in endoscopic ultrasound and Japanese clinical diagnostic criteria for chronic pancreatitis. Results: The prevalence of male was higher than female (70.5%/29.5%) and most common in the age group of 41 - 60 about 55%. The prevalence of patients with a history of alcohol abuse was highest with 31.3%, smoking cigarette more than 20 pack-years about 4.1%. The clinical characteristics of patients with chronic pancreatitis are highest in abdominal pain about 66.6% and lowest in jaundice about 5.8%. About biochemical characteristics, an increase of amylase, lipase were found in 29.5% and 31.5%, respectively. The diabetes mellitus were found in 25.6%. A statistically significative difference of abdominal pain was found between the chronic pancreatitis and early chronic pancreatitis patients (p=0.0003). Mean level of lipase in chronic pancreatitis patient is 33.7 U/L(3.3-195) and early chronic pancreatitis patient is 53.1 U/L (20.5-109), with significiant difference (p=0.04). Conclusions: Alcohol consumption, heavy smoking and diabetes mellitus were the most important risk factors of chronic pancreatitis. Abdominal pain was constant while hyperamylasemia and hyperlipasemia was found only in 29.5% and 31.5% patients. Rate of abdominal pain and mean level of serum lipase were different between chronic pancreatitis and early chronic pancreatitis patients. Key words: chronic pancreatitis, endoscopic ultrasound

Abstract 1249: Animal model in the prevention of alcoholic pancreatitis

Abstract Background: Alcohol abuse is a major risk factor for pancreatitis. Alcohol addiction-induced molecular pathogenesis of pancreatitis remains obscure, and no current effective treatment exists. Therefore, approaches to investigate pathogenesis, prevention and cellular mechanisms by which alcohol causes pancreatitis are necessary for establishing therapeutics. Our efforts demonstrate that alcohol induces activation of a major intracellular transcriptional factor, cyclic AMP response element-binding protein (CREB). We further investigated the functional role of CREB in alcohol-induced pathogenesis of pancreatitis using cellular and genetic mouse models of pancreas. Materials and Methods: Human tissue microarrays were immunostained to determine the significance of pCREB expression among pancreatic tissues obtained from normal and chronic pancreatitis. Rat acinar cell line AR42J and mouse PSCs (mPSCs) were exposed to alcohol (50 mMol/L). Inducible Ptf1aCreERTM knockin mice and Ptf1aCreERTM;CREBfl/fl (iPC) mice were fed with Lieber Decarli diet alcohol or regular diet for 14 weeks with or without caerulein (50 µg/kg). Mice were then euthanized 24 hours after the last caerulein injection, and pancreas tissues were processed for morphometric analysis (necrosis, vacuolization, hemorrhage, edema and inflammation) and immunohistochemical analysis of amylase, trichrome blue, SMA, collagen 1, fibronectin and pCREB expression. To determine whether alcohol accelerated morbidity in mice, we evaluated pathogenesis of chronic pancreatitis by analyzing acinar atrophy and pancreatic fibrosis. Results: Expression of pCREB was significantly higher (p &amp;lt;0.001) in chronic pancreatitis vs. normal patient tissues, confirming the role of activated CREB in pancreatitis. Activated CREB levels were very high in alcohol-fed Ptf1aCreERTM mice when compared with control diet-fed mice. Pancreatic sections from alcohol-fed mice challenged with caerulein revealed significantly higher score of acinar cell vacuolization and necrosis, inflammatory infiltrate and hemorrhage compared with minimal lesions in control diet-fed animals receiving caerulein. Pancreatic sections from alcohol-fed Ptf1aCreERTM animals showed higher score of histologic injury, extracellular matrix deposition, collagen deposition and increased pancreatic fibrosis when compared with control-fed mice. iPC mice showed decrease in the pathogenesis of chronic pancreatitis when compared to Ptf1aCreERTM mice with alcohol. Conclusion: CREB is overexpressed in pancreatitis and alcohol activates CREB, which then drives pathogenesis of pancreatitis. Severity of pancreatitis in response to alcohol is diminished in the absence of CREB. Therefore, we conclude that targeting CREB represents a promising treatment for alcohol-induced pancreatitis. Citation Format: Supriya Srinivasan, Tulasigeri Totiger, Michael VanSaun, Fanuel Messaggio, Chanjuan Shi, Austin Dosch, Eric Nestler, Nipun Merchant, Nagaraj Nagathihalli. Animal model in the prevention of alcoholic pancreatitis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1249.

Hydrogen Treatment Protects Mice Against Chronic Pancreatitis by Restoring Regulatory T Cells Loss

Background/Aims: Chronic pancreatitis is an inflammatory disease of the pancreas characterized by progressive tissue destruction and fibrogenesis. The development of chronic pancreatitis is associated with immune cell dysregulation. Currently, the specific and effective treatment of chronic pancreatitis remains absent. Methods: By using an L-arginine induced chronic pancreatitis mouse model, we tested the therapeutic potential of hydrogen, a strong hydroxyl radicals scavenger, in the chronic pancreatitis model. Tissue inflammation, damage and fibrosis were analyzed on HE, TUNEL, MPO, and sirius staining. Pancreas levels of MDA content, SOD activity, TNF-α , IL-10 cytokine expression and serum amylase and lipase activity were determined by ELISA and absorbance assay. Apoptosis, T cells subtype proportion and intracellular level of reactive oxygen species (ROS) were analyzed by flow cytometry. Tregs adoptive transfer and CD25 neutralization were used to validate the role of Tregs in chronic pancreatitis. Results: We found that hydrogen treatment significantly improved multiple symptoms of chronic pancreatitis. The number of Tregs was reduced in chronic pancreatitis mice, while hydrogen treatment restored the Treg loss by L-arginine administrations. Depletion of Tregs abolished the protective effect of hydrogen treatment in chronic pancreatitis. In vitro study showed that hydrogen blocked ROS generation in Tregs and promoted Tregs survival. Conclusion: Hydrogen treatment showed reliable benefits in controlling the severity of chronic pancreatitis. Our study supported that hydrogen could be used as a novel treatment in chronic pancreatitis patient in the future.

Telephone-Based Mindfulness Therapy Intervention for Patients with Chronic Pancreatitis.

Patients with chronic pancreatitis (CP) have substantially impaired quality of life (QOL) both physically and mentally. Mindfulness therapy is a form of treatment that has been shown to be beneficial in many medical conditions but has not been evaluated in the CP patient population. The aims of this study were (1) to test the feasibility and usability of a novel telephone-based mindfulness therapy service for patients with CP and (2) to determine whether there was any effect on CP quality of life. We recruited ten patients with suspected or confirmed CP and five controls who were asked to utilize our telephone-based mindfulness therapy service daily for 28days. Feasibility of the service was defined as the fraction of subjects with a≥50% compliance rate. Usability was assessed using a System Usability Scale (SUS). QOL was evaluated using the SF-36 questionnaire and the Pancreatitis Quality of Life Instrument (PANQOLI). Paired t tests were used to compare the SF-36 and PANQOLI pre- and post-intervention. There was an overall compliance rate of 67%. The mean SUS score for all participants was 79.3, above the average published score of 68. Results showed a significant improvement in the SF-36 Mental Component Summary scores after 28days of mindfulness therapy for patients with CP, t(9)=2.48, p=0.035. There was also a significant improvement in the mean total PANQOLI scores in CP patients, t(9)=2.41, p=0.04, most notably in the social domain. Our telephone-based mindfulness therapy service represents a feasible and easily usable treatment adjunct for patients with CP, which may provide benefit in QOL by improving mental health-related domains.

Utility of MicroRNAs in Differentiating Pancreatic Cancer and Autoimmune Pancreatitis

Introduction: Distinguishing pancreatic ductal adenocarcinoma (PDAC) from autoimmune pancreatitis (AIP) remains a challenge. Better diagnostic markers are needed to diagnose AIP. MicroRNAs (miRNA) are important biomarkers in diagnosis of pancreatic cancer. Aim: This pilot study seeks to identify whether a 7-miRNA panel developed for distinguishing PDAC from benign pancreatic lesions in fine needle aspirates (FNA) can also help differentiate PDAC from chronic pancreatitis (CP) and AIP. Methods: 34 formalin fixed, paraffin embedded (FFPE) specimens were selected: 1) 15 PDAC, 2) 13 AIP 3) 6 CP. Total RNA extraction was performed using protocols developed at Asuragen followed by interrogation of expression levels of previously published miRInform Pancreas Test consisting of a 7-miRNA panel (miR-24, -96, -130b, -135b, -148a, -196a and -375) using TaqMan® MicroRNA Assays. The test score was calculated for each sample using proprietary bioinformatics algorithms with 0.5 to 1, inclusive, consistent with PDAC, and the results compared to histological evaluation. Results: Mean age of the 34 patients was 54±17 years with 50% female. Symptoms were present in 78% of AIP (abdominal pain), 80% of CP (abdominal pain, recurrent pancreatitis in 1 patient), and 50% of PDAC patients (painless jaundice and abdominal pain) (p=0.6). Serum CA 19-9 was not elevated in patients with AIP or CP while abnormal in 1 patient with PDAC. Cytology was available in 4 AIP with none diagnostic; 1 was suspicious for adenocarcinoma and 1 consistent with adenocarcinoma. Cytology was performed in 1 CP patient and showed atypical cells; 75% of PDAC patients had diagnostic cytology. miRNA expression profiling was successfully completed on 32 FFPE samples (2 AIP samples did not yield adequate RNA). None of the 11 AIP and 6 CP specimens had a test score indicating PDAC, while 9 of 15 PDAC samples had a score consistent with PDAC. Sensitivity of the 7-miRNA classifier was 60% [95% CI 32-84], specificity 100% [95% CI 80-100], positive predictive value 100% [95% CI 66-100], and negative predictive value 74% [95% CI 52-90]. Conclusion: - The 7-miRNA classifier miRInform Pancreas test can help differentiate AIP and CP from PDAC in FFPE specimens. - Future implication: Endoscopic ultrasound-guided FNA of pancreatic masses combined with the 7-miRNA classifier may improve the ability to differentiate AIP from pancreatic adenocarcinoma.

Combined Medical Treatment Of Chronic Pancreatitis

Abstract The aim of the study was to determine the most effective medical treatment of patients with chronic pancreatitis, by using either pancreatin alone or in combination with proton pump inhibitor (PPI) or PPI and non-steroidal anti-inflammatory drug (NSAID). Patients with chronic pancreatitis, who did not require a surgical treatment, received medical treatment for a one–month period: 20 patients received pancreatin monotherapy; 48 patients were given a combination of pancreatin and PPI; 38 patients were treated with a combination of pancreatin, PPI and NSAID (PNP therapy group). In comparison with other groups, patients in the PNP therapy group showed improvement in body mass index, abdominal pain, bowel movements, chronic pancreatitis severity, as well as their quality of life assessment (p &lt; 0.05). The combination of pancreatin, PPI and NSAID was the most effective among those applied in chronic pancreatitis patient treatment. A one–month long course of this therapy was safe and did not cause any significant adverse effects. The combination of pancreatin, PPI and NSAID for treatment of chronic pancreatitis can be recommended, as it is based on pathogenesis of the disease, effective, safe and economically advantageous.

Relationship between autoimmune pancreatitis and pancreatic cancer: A single-center experience

ObjectivesOrdinary chronic pancreatitis (CP), such as alcoholic CP, is well established to have the increased risk for pancreatic cancer (PaC), nevertheless an association between autoimmune pancreatitis (AIP) and PaC is still unknown. The aims of this study are to examine the frequency of patients who developed PaC during follow-up after being diagnosed with type 1 AIP and to compare the incidence rate of PaC between patients with type 1 AIP and CP. MethodsSixty-three patients with type 1 AIP and 41 patients with CP were enrolled. We examined development of PaC during follow-up from their clinical records. ResultsThe mean follow-up period was 62.4 months in AIP group and 49.2 months in CP group. The occurrence of PaC was observed in 3 patients with AIP during the mean follow-up period of 94.7 months (range, 31–186), whereas a single CP patient developed PaC 38 months after CP diagnosis. The incident rate of PaC during follow-up was comparable between the 2 groups [4.8% (3/63) in type 1 AIP group vs. 2.4% (1/41) in CP group]. In all of 3 AIP patients who developed accompanying PaC, the clinical remission of AIP was achieved with maintenance steroid therapy, when tumors were discovered. In the histological examination of one surgical patient with PaC, lymphoplasmacytic infiltration in storiform fibrosis with abundant IgG4-positive cell infiltration was observed around the PaC area. ConclusionsSimilar to patients with ordinary CP, surveillance for development of PaC is needed at regular interval during follow-up in AIP patients.

Impact of pancreatic comorbidities in patients with end-stage liver disease on outcome after liver transplantation

BackgroundDiseases leading to end-stage liver disease (ESLD), especially alcoholic liver cirrhosis cause comorbidities of the pancreas, too. The aim of this retrospective study was to determine the impact of pancreatic alterations diagnosed pretransplant on the outcome after liver transplantation (LT). MethodsIn total, data from 372 LT patients were analyzed. Patients were followed up for a mean of 4.2years. Incidence of chronic pancreatitis (CP), pancreatic cysts (PC) and intraductal papillary mucinous neoplasm (IPMN) was acquired retrospectively from patient's charts. ResultsCP, IPMN and PC were rarely diagnosed in LT-recipients [CP (3.8%), PC (1.6%) and IPMN (1.6%)]. There was no significant correlation of IPMN, CP, PC and other patient characteristics. The prevalence of CP (log rank: p=0.315), PC (log rank: p=0.242) and IPMN (log rank: p=0.491) did not influence patient survival. ConclusionFrequency of radiological alterations of the pancreas in LT recipients (such as CP, PC, IPMN) diagnosed by sonography, CT scan or MRI is comparable to the non-transplant population. Short term survival of LT-recipients after transplantation is not reduced for patients with CP, PC and patients with branch-duct IPMN (with a low-risk for malignancy according to international consensus guidelines).