Therapy Of Chronic Pancreatitis Research Articles

YAP promotes fibrosis by regulating macrophage to myofibroblast transdifferentiation and M2 polarization in chronic pancreatitis.

Chronic pancreatitis (CP) is a clinical entity characterized by progressive inflammation and irreversible fibrosis of the pancreas, which ultimately leads to exocrine and/or endocrine insufficiency as well as an increased risk of pancreatic cancer. Currently, there are no specific or effective approved therapies for CP. Herein, we show that macrophage to myofibroblast transdifferentiation (MMT) and M2 macrophage polarization are associated with both human CP and CP experimental mouse models. In addition, we show YAP is activated in macrophages during CP. Furthermore, we used the YAP agonist XMU-MP-1 (XMU) and the YAP inhibitor Verteporfin (VP) to modulate YAP expression levels. In vitro experiments revealed that XMU upregulated YAP expression, thereby promoting MMT and enhancing M2 macrophage polarization; conversely, VP downregulated YAP expression, inhibiting these effects. In vivo studies indicated that XMU exacerbated acinar cell atrophy and interstitial fibrosis in caerulein-induced mouse models of CP, while VP mitigated these adverse effects associated with CP. These findings provide new insights into the pathogenic mechanisms underlying CP, and offer potential therapeutic targets for CP.

Tcf21 Alleviates Pancreatic Fibrosis by Regulating the Epithelial-Mesenchymal Transformation of Pancreatic Stellate Cells.

The activation of pancreatic stellate cells (PSCs) plays a key role in the occurrence and development of chronic pancreatitis (CP) and pancreatic fibrosis, which is related to the process of epithelial-mesenchymal transition (EMT). This study was designed to investigate the effect and mechanism of Tcf21 (one of tumor suppressor genes) on pancreatic inflammation and fibrosis in vivo and in vitro. C57BL/6 male mice were intraperitoneally injected with caerulein for 6weeks to establish CP animal model. Fixed pancreatic tissue paraffin-embedded sections were used for immunohistochemistry staining of Tcf21, fibrosis-related markers (α-SMA), interstitial markers (Vimentin) and epithelial markers (E-cadherin). Western blotting and qRT-PCR assay were performed to analyze the change of expression of the above markers after stimulation of TGF-β1 or overexpressed Tcf21 lentivirus transfection in human pancreatic stellate cells (HPSCs). The pancreatic expression of α-SMA and Vimentin of CP mice significantly increased, while the expression of Tcf21 and E-cadherin significantly decreased. TGF-β1 could promote activation and EMT process of HPSCs, and inhibited the expression of Tcf21. Overexpression of Tcf21 could significantly down-regulate the expression of α-SMA, Fibronectin and Vimentin, and up-regulated the expression of ZO-1 of HPSCs. Cell Counting Kit-8 assay and scratch wound-healing assay results showed that overexpression of Tcf21 could significantly inhibit the cell migration and proliferation of HPSCs. Overexpression of Tcf21 could significantly alleviate the activation, proliferation, migration of PSCs by regulating the EMT process. Tcf21 had a potential prospect of a new target for CP therapy.

Immune cells and immune cell-targeted therapy in chronic pancreatitis.

In recent years, studies have attempted to understand the immune cells and mechanisms underlying the pathogenesis of chronic pancreatitis (CP) by constructing a model of CP. Based on these studies, the innate immune response is a key factor in disease pathogenesis and inflammation severity. Novel mechanisms of crosstalk between immune and non-immune pancreatic cells, such as pancreatic stellate cells (PSC), have also been explored. Immune cells, immune responses, and signaling pathways in CP are important factors in the development and progression of pancreatitis. Based on these mechanisms, targeted therapy may provide a feasible scheme to stop or reverse the progression of the disease in the future and provide a new direction for the treatment of CP. This review summarizes the recent advances in research on immune mechanisms in CP and the new advances in treatment based on these mechanisms.

A new method for treating chronic pancreatitis and preventing fibrosis using bioactive calcium silicate ion solution.

Chronic pancreatitis (CP) is a multifactorial fibroinflammatory syndrome. At present, there is no effective way to treat it clinically. In this study, we proposed a new approach by application of a highly active calcium silicate ion solution derived from calcium silicate (CS) bioceramics, which effectively inhibited the development of CP. This bioceramic derived bioactive ionic solution mainly regulated pancreatic acinar cells (PACs), macrophages and pancreatic stellate cells (PSCs) by SiO32- ions to inhibit inflammation and fibrosis and promote acinar regeneration. The possible mechanism of the therapeutic effect of CS ion solution mainly includes the inhibition of PAC apoptosis by down-regulating the c-caspase3 signal pathway and promotion of the regeneration of PACs by up-regulating the WNT/β-catenin signaling pathway. In addition, the CS ion solution also effectively down-regulated the NF-κB signaling pathway to reduce macrophage infiltration and PAC inflammatory factor secretion, thereby reducing PSC mediated pancreatic fibrosis. This bioceramics-based ion solution provides a new idea for disease treatment using biomaterials, which may have the potential for the development of new therapy for CP.

Effectiveness of Differentiated Hepatotrophic Therapy in Complex Management of Patients with Comorbidity of Chronic Pancreatitis and Chronic Viral Hepatitis С

An important problem of the combined course of chronic pancreatitis (CP) and chronic hepatitis C virus (HCV) is the study of the effects of chronic HCV, even after the treatment, in particular for the condition of the pancreas and liver in patients with CP. Often hepatotrophic therapy is used for this purpose, which should be differentiated depending on the needs of patients with comorbidity of CP and chronic HCV. The objective: to analyze the functional and structural condition of the pancreas and liver in patients with CP after the chronic HCV treatment by the proposed complex treatment with additional inclusion of hepatotrophic drugs. Materials and methods. 80 patients with a combined course of CP and chronic HCV were examined. According to the methods of treatment the patients were divided into three groups. The 1st group included 20 patients with CP and chronic HCV, who received a common complex for treatment (CCT) by protocol for 3 months. In the 2d group 25 patients with CP and chronic HCV received CCT with additional inclusion of hepatotrophic agent for 3 months. The 3d group included 35 patients with CP and chronic HCV with CAGE≥2.0, who took CTC with additional inclusion of hepatotrophic agent for 3 months and metadoxine for 3 months. Results. The more significant level of efficiency of therapeutic complex with the additional inclusion of hepatotrophic agent was determined when metadoxine was prescribed. It was found that the content of fecal α-elastase increased by 19.6 %, 37.5 % and 66.9 %, glucose level decreased by 13.4 %, 11.0 % and 28.4 %, glyconized hemoglobin – by 12.3 %, 22.1 % and 25.8 %, HOMA index – by 16.3 %, 21.9 % and 56.0 %, coprogram score – by 12.8 %, 18.3 % and 88.7 %, the total index of the pancreas structure – by 7.2 %, 15.1 % and 85.7 %, and the total indicator of liver structure – by 11.7 %, 17.5 % and 44.7 %, respectively in groups (p<0.05). It was established that the inclusion of the hepatotrophic medicine in the standard therapy of CP with chronic HCV improved the results of treatment for the restoration of the functional and structural condition of the pancreas. Conclusions. The additional prescription of the hepatotrophic agents combination significantly increased the effectiveness of treatment according to the dynamics of the functional capacity of pancreas and restoration of its structure (p<0.05). It was confirmed that a complex medical program with additional use of polysubstrate hepatoprotector exceeded the efficiency of the protocol treatment for the structural condition of the liver by 36.0 %, and with a combination of hepatotrophic agents – by 51.9 %; regarding the pancreas condition – by 22.3 % and 38.3 %, respectively (p<0.05). The combined use of hepatotrophic agents was also more effective than monotherapy with one drug.

Medical nutritional therapy in chronic pancreatitis

Chronic pancreatitis is a complex disease associated with significant morbidity and mortality. Patients with chronic pancreatitis are at risk for malnutrition and nutrient deficiency caused primarily by malabsorption, inadequate intake, and inflammation. Poor nutritional status may negatively affect disease’s outcome. Medical nutritional therapy which include screening and assessment of malnutrition followed by optimal nutritional intervention for patient at risk should be the cornerstone of chronic pancreatitis multidisciplinary treatment.

Elevated islet prohormone ratios as indicators of insulin dependency in auto-islet transplant recipients

Pancreatic islet transplantation has therapeutic potential in type 1 diabetes and is also an established therapy in chronic pancreatitis. However, the long-term transplant outcomes are modest. Identifying indicators of graft function will aid the preservation of transplanted islets and glycemic control. We analyzed beta cell prohormone peptide levels in a retrospective cohort of total pancreatectomy autologous islet transplant patients (n = 28). Proinsulin-to-C-peptide (PI/C) and proIAPP-to-total IAPP (proIAPP/IAPP) ratios measured at 3 months post-transplant were significantly higher in patients who remained insulin dependent at 1 year follow-up. In an immuno-deficient mouse model of human islet transplantation, recipient mice that later became hyperglycemic displayed significantly higher PI/C ratios than mice that remained normoglycemic. Histological analysis of islet grafts showed reduced proportional insulin- and proinsulin-positive area, but elevated glucagon-positive area in grafts that experienced greater secretory demand. Increased prohormone convertase 1/3 was detected in glucagon-positive cells, and glucagon-like peptide 1 (GLP-1) area was elevated in grafts from mice that displayed hyperglycemia or elevated plasma PI/C ratios, demonstrating intra-islet incretin production in metabolically challenged human islet grafts. These data indicate that in failing grafts, alpha cell prohormone processing is likely altered, and incomplete beta cell prohormone processing may be an early indicator of insulin dependency.

Nutrition therapy in acute and chronic pancreatitis.

Pancreatitis is an inflammatory disease associated with disorders of nutrient assimilation and, as a result, with significant changes in the nutritional status. All patients with acute pancreatitis should be considered at nutritional risk and should be screened using validated screening methods. The optimal nutritional treatment for acute pancreatitis has been debated for decades. The traditional approach was "nothing in the mouth", only parenteral nutrition until the acute symptoms disappear and the level of serum pancreatic enzymes decreases. However, this tactic can contribute to various complications, starting with malnutrition and ending with sepsis due to damage of the intestinal mucosa. Clinical trials and meta-analyses have shown that patients with acute pancreatitis can tolerate oral nutrition and that oral / enteral nutrition is associated with a shorter hospital stay and a lower rate of complications compared to solely parenteral. Therefore, early oral nutrition with a low-fat "soft food" is recommended. In case of oral feeding intolerance, enteral nutrition is preferable, but not parenteral supply. A combination of enteral and parenteral nutrition may be recommended in patients who do not tolerate a sufficient amount of enteral nutrition. Malnutrition in chronic pancreatitis cannot be detected using BMI alone, and a detailed nutritional assessment is required, including assessment of symptoms and organic functions, anthropometry, and biochemical tests. Nutritional therapy in chronic pancreatitis should be multifactorial and based on abstinence from alcohol and nicotine, and diet modification. International guidelines no longer recommend severe dietary fat restriction; on the contrary, a physiological diet is recommended, but with adequate replacement of pancreatic enzymes. In case of intolerance to physiological nutrition, a low-fat diet with oral nutritional supplements is recommended to replenish energy and nutrients. This is a review of recent studies and guidelines on nutrition in pancreatitis for physicians and medical trainees.

Is it necessary to correct the intestinal microbiota disorders in chronic pancreatitis?

The frequency of intestinal microbiota disorders in patients with chronic pancreatitis (CP) is extremely high and can reach 97%. The bacterial overgrowth syndrome (SIBO) and the syndrome of increased epithelial permeability (SPEP), developing against the background of excretory insufficiency of the pancreas, affect the severity of the clinical picture of the disease, reduce the effectiveness of enzyme replacement therapy and generally contribute to the further progression of CP.The article presents a modern view on the mechanisms of the formation of SIBO and SPEP in CP. There is their aggravating effect on the course of the disease and the aggravation of disorders of the digestive and absorption processes that accompany them is shown and analyzed in the article.For decontamination of conditionally pathogenic and pathogenic flora, increasing the number and metabolic activity of indigenous microflora in patients with CP, the use of a non-absorbable broad-spectrum antibiotic rifaximin is effective. In order to restore the barrier function of the gastrointestinal mucosa, the drug of choice is rebamipid, a universal cytoprotector that affects all three levels of epithelial tissue protection (preepithelial, epithelial and subepithelial).Conclusion. CP is characterized by the complexity of its etiology and pathogenesis. Bacterial factors, in particular, SIBO and SPEP, play an essential role in the development of inflammatory changes in the pancreas. In the complex therapy of CP, it is advisable to take measures aimed at correcting disorders of the intestinal microbiota.

Surgery for chronic pancreatitis: the comparison of two high-volume centers reveals lack of a uniform operative management

PurposeMany aspects of surgical therapy for chronic pancreatitis (CP), including the correct indication and timing, as well as the most appropriate operative techniques, are still a matter of debate in the surgical community and vary widely across different centers. The aim of the present study was to uncover and analyze these differences by comparing the experiences of two specialized surgical units in Italy and Austria.MethodsAll patients operated for CP between 2000 and 2018 at the two centers involved were included in this retrospective analysis. Data regarding the clinical history and the pre- and perioperative surgical course were analyzed and compared between the two institutions.ResultsOur analysis showed a progressive decrease in the annual rate of pancreatic surgical procedures performed for CP in Verona (no. = 91) over the last two decades (from 3% to less than 1%); by contrast, this percentage increased from 3 to 9% in Vienna (no. = 77) during the same time frame. Considerable differences were also detected with regard to the timing of surgery from the first diagnosis of CP — 4 years (IQR 5.5) in the Austrian series vs two (IQR 4.0) in the Italian series -, and of indications for surgery, with a 12% higher prevalence of groove pancreatitis among patients in the Verona cohort.ConclusionThe comparison of the surgical attitude towards CP between two surgical centers proved that a consistent approach to this pathology still is lacking. The identification of common guidelines and labels of surgical eligibility is advisable in order to avoid interinstitutional treatment disparities.

Natural course of pain in chronic pancreatitis is independent of disease duration

ObjectivesPain burn-out during the course of chronic pancreatitis (CP), proposed in the 1980s, remains controversial, and has clinical implications. We aimed to describe the natural course of pain in a well-characterized cohort. MethodsWe constructed the clinical course of 279 C P patients enrolled from 2000 to 2014 in the North American Pancreatitis Studies from UPMC by retrospectively reviewing their medical records (median observation period, 12.4 years). We assessed abdominal pain at different time points, characterized pain pattern (Type A [short-lived pain episodes] or B [persistent pain and/or clusters of recurrent severe pain]) and recorded information on relevant covariates. ResultsPain at any time, at the end of follow-up, Type A pain pattern or B pain pattern was reported by 89.6%, 46.6%, 34% and 66% patients, respectively. In multivariable analyses, disease duration (time from first diagnosis of pancreatitis to end of observation) did not associate with pain - at last clinical contact (OR, 1.0, 95% CI 0.96–1.03), at NAPS2 enrollment (OR 1.02, 95% CI 0.96–1.07) or Type B pain pattern (OR 1.01, 95% CI 0.97–1.04). Patients needing endoscopic or surgical therapy (97.8 vs. 75.2%, p < 0.001) and those with alcohol etiology (94.7 vs. 84.9%, p = 0.007) had a higher prevalence of pain. In multivariable analyses, invasive therapy associated with Type B pain and pain at last clinical contact. ConclusionsOnly a subset of CP patients achieve durable pain relief. There is urgent need to develop new strategies to evaluate and manage pain, and to identify predictors of response to pain therapies for CP.

Malnutrition after pancreatic enzyme replacement therapy in chronic pancreatitis: Risk factors in real world practice

BackgroundRCTs that have shown improvement in coefficient of fat absorption with pancreatic enzyme replacement therapy (PERT) have seldom evaluated the impact on overall nutritional status. ObjectiveIn this study we evaluated factors responsible for persistence of malnutrition after PERT. MethodsIn this cross-sectional observational study, patients were enrolled based on predefined enrolment criteria. Patients were divided into those taking PERT regularly (Group A), irregularly (Group B) and not taking (Group C) for at least 3 months. Comprehensive evaluation of anthropometric measurements, nutritional assessment and dietary intake was performed. Malnutrition was measured using the Subjective Global Assessment (SGA) tool. Relationship between PERT status, dietary intake and nutritional status were evaluated using standard statistical methods. Logistic regression was performed to identify factors associated with persistence of malnutrition after PERT. Results377 patients with CP and 50 controls were included. 95 (25.2%) patients with CP were in Group A, 106 (28.1%) in Group B and 176 (46.7%) in Group C. 130 (34.5%) patients were malnourished, of which 76 (58.5%) were continuing PERT. There were no differences in clinical and biochemical nutritional markers between Groups A, B, and C. Calorie deficit and daily intake of calorie, protein, carbohydrates and fats were not different between those with and without PERT, but was significantly less in those with malnutrition. Logistic regression demonstrated inadequate dietary intake as independent risk factor for persistence of malnutrition. ConclusionEven though PERT is effective in PEI, comprehensive nutritional assessment, personalized nutritional counselling and therapy along with PERT is mandatory.

Suboptimal care for chronic pancreatitis patients revealed by moderate to low adherence to the United European Gastroenterology evidence-based guidelines (HaPanEU): A Netherlands nationwide analysis.

Background and objectiveThe 2016, United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis (HaPanEU) provided evidence-based recommendations for the management of chronic pancreatitis and allowed for the objective evaluation of the quality of care in several domains of disease management through assessment of guideline adherence. Therefore, the aim of this study is to evaluate the current level and the variety of care for chronic pancreatitis patients in the Netherlands using the HaPanEU guidelines as a reference standard. The majority of these patients were diagnosed before the publication of these guidelines. Therefore, in most patients, the results of the present study with respect to those recommendations regarding the diagnostic process of chronic pancreatitis represent guideline correspondence and not adherence.MethodsA subgroup of patients from the Dutch nationwide chronic pancreatitis registry (CARE) was included in a retrospective cross-sectional observational cohort study. A total of 39 recommendations concerning the non-invasive management of chronic pancreatitis were appointed as quality indicators (QIs). Per patient, the number of relevant QIs was determined and guideline adherence was assessed. Data were analyzed to identify factors associated with guideline adherence.ResultsOverall, 97 patients with chronic pancreatitis from 11 hospitals were included. Per patient, a mean number of 26 relevant QIs was applicable, with an average adherence rate of 53%. In 45% of the patients, guideline adherence was less than 50%. The majority of suboptimal managed QIs concerned the management of chronic pancreatitis complications. Guideline adherence was not associated with hospital type, sex, age or etiology of pancreatitis.ConclusionIn the Netherlands, adherence to the HaPanEU recommendations for the management of chronic pancreatitis is moderate to low for all non-invasive domains, which may indicate suboptimal care for these patients. Closer guideline adherence could improve the level of care and the clinical outcomes of these patients. A nationwide approach to increase awareness of the key guideline recommendations among clinicians and patients is needed.

Pancreatology: debunked myths

Enzyme replacement therapy is not always effective enough upon exocrine pancreatic insufficiency. One of the main reasons is myths — doctors’ misconceptions about the indications and rules of replacement therapy.&#x0D; In particular, there is an outdated opinion about the effectiveness of tablet enzyme preparations used for the relief of pancreatic pain. However, a number of evidence-based studies have proved that enzyme preparations are not effective enough to relieve pain in chronic pancreatitis, and thus should not be used for this purpose. This statement is recorded in the United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis, as well as in the recommendations of the American College of Gastroenterology. In addition, tablet preparations are characterized by asynchronism of the passage of the chyme and the tablet along the digestive tract.&#x0D; The second myth is that drugs without an acid-resistant coat start hydrolyzing the components of the chyme in the stomach, which ensures higher efficiency as compared to Creon. But in the absence of a coat, enzymes are inactivated in the acidic environment of the stomach and cannot have any effect at all.&#x0D; The third myth is that enzyme preparations always cause constipation. In fact, constipation occurs in no more than 10% of cases. They are usually associated with an overdose of the drug, concomitant pathology or insufficient compliance.&#x0D; The fourth myth is that prescribing the doses of enzyme preparations indicated in the European Guidelines causes addiction. It is crucial to know that such doses do not exceed 10% of the pancreas’s own capacities, therefore, they cannot significantly affect these capabilities, which is also demonstrated by evidence-based studies.&#x0D; The fifth myth is that patients gain weight because of enzyme preparations, and they should not be prescribed upon overweight and obesity. Numerous data firmly show that pancreatic insufficiency often occurs in such cases, and enzyme preparations are required.&#x0D; The sixth myth is that a drug with a different composition can be produced under the usual established product name. For example, NEO is added to the name to “mask” a drug with a new composition. Doctors should carefully monitor the composition of such drugs.&#x0D; The seventh myth is that a minimicrospherical preparation (Creon) is as effective as microspherical preparation. However, this statement turned out to be a myth as well. Minimicrospherical preparations are proved to be significantly more effective in clinical practice.&#x0D; Thus, the above-mentioned myths, like many others, are based on insufficient knowledge in the field of pancreatology.

Indications for Surgical Therapy in Chronic Pancreatitis

Chronic pancreatitis is a recurrent disease with repeating exacerbations of inflammation of the pancreatic gland - associated with belt-like back pain. Without treatment, recurrent chronic pancreatitis leads to development of opioid-dependent pain. The chronic pancreatitis leads to recurrent hospital stays for the affected patient and socioeconomic challenges. In progress it can lead to local complications of chronic pancreatitis, such as formation of pseudocysts, biliary duct obstruction, duodenal obstruction or portal hypertension. The aim of this article is a detailed description of the indication for surgical therapy in chronic pancreatitis. The underlying analysis was a systematic literature research and evaluation, the formulation of key questions according to the PICO system and the evaluation of indications and key statements and questions, as implemented in a three level Delphi process among the members of the pancreas research group and the indications for the surgery group of the German Society of General and Visceral Surgery (DGAV). Surgical resection of the inflammatory pancreatic head pseudotumour, after initial conservative therapy, is a highly efficient therapy for the control of pain and the avoidance of complications in chronic pancreatitis. For this purpose, well evaluated surgical strategies are available. Delay in surgical therapy can lead to chronic pain, kachexia and malnutrition and increase complications of surgical therapy.

Chronic pancreatitis is an acid dependent disease. Which mark to put at the end of the sentence: interrogative, exclamation, dot or ellipsis?

Chronic pancreatitis (CP) is one of the most widespread gastroenterological diseases, the pathogenic mechanisms of which are still under investigation. The authors gave a short overview of the main stages in the research of the relationships between gastric and pancreatic secretion, and the results of physiological studies, performed by I. P. Pavlov and his students. Being а strict follower of «nervousness» theory, the great physiologist and his associates made the incorrect conclusions about the presence of local nerve connections (peripheral reflex arc) between the duodenum and pancreas, not suggesting the presence of humoral interactions. The modern data have been presented that give the evidence that duodenal acidification results in the secondary deficiency of endogenous pancreatic enzymes, increased stimulation of pancreatic secretion, exacerbated symptoms of exocrine pancreatic insufficiency, increased secretory tension in pancreatic tissue, duct and tissue pressure, and increased risk of CP attack.However, a dot at the end of a statement «CP is an acid-dependent disease» is tentative. The proton pump inhibitors (PPIs) are used throughout for the treatment of acid-dependent diseases. However, neither European, nor Russian recommendations do include PPIs as a basic treatment for CP. The results of a prospective randomized controlled trial, which proved the effectiveness of CP treatment with the use of combination of analgesics and PPIs have been considered. However, the results of the only study are not enough to recommend the inclusion of PPI in the basic CP therapy. The analysis has been performed for the provisions of the European Guidelines for the Diagnosis and Treatment of Pancreatitis. These guidelines describe situations when PPIs should be included in the complex CP treatment. The data of evidence-based medicine have been presented, illustrating that suppression of gastric secretion can increase the effectiveness of enzyme preparations in comparison with the administration of pancreatin monotherapy. The advantages of pantoprazole among other of the PPIs’ representatives have been analyzed. A clinical case of CP treatment with a reasonable pantoprazole (Nolpaza) administration have been considered.

2182 Endoscopic Challenges in a Patient With Ansa Pancreatica and Recurrent Pancreatitis

INTRODUCTION: Ansa pancreatica is a rare anatomical variation of the pancreatic duct where there is communication between the ventral pancreatic duct, which forms an ansa loop, and the accessory pancreatic duct. Its prevalence is estimated to be 1% in general population, and its presence can predispose to acute pancreatitis. We present an interesting and rare case of chronic pancreatitis with a pancreatic duct stricture in the setting of ansa pancreatica. CASE DESCRIPTION/METHODS: A 54-year-old female with a heterozygous CFTR mutation and a long-standing history of recurrent acute and now chronic pancreatitis. Two weeks after an episode of acute pancreatitis, a magnetic resonance cholangiopancreatography (MRCP) was performed showing a new stricture in the pancreatic duct near the genu, with pre-stenotic ductal dilation. Two prior endoscopic retrograde cholangiopancreatographies had been performed to attempt pancreatic duct endotherapy, but these were unsuccessful in achieving deep wire cannulation beyond the ansa loop. (image 1A-1B). The pancreatic duct in the genu of the pancreas was noted to have moderate stenosis on MRCP (image 1C). After a discussion with the patient, the decision was made to re-attempt endoscopic therapy. The ventral pancreatic duct was initially cannulated. The 0.025 inch angled guidewire was again unable to navigate the ansa loop and into the distal pancreas. Thereafter, we attempted dorsal pancreatic duct cannulation via the monir papilla. The guidewire was advanced successfully beyond the stricture and into the opacified body and tail (image 1D). The minor papilla and the stricture in the genu were dilated with a 7 Fr catheter dilator. After a minor papillotomy a 7 Fr by 8 cm plastic stent was placed into the dorsal pancreatic duct (image 1E, 2). The stent was removed 6 weeks later, and the duct remained patent. The patient has had no recurrence of acute pancreatitis to date. DISCUSSION: While the prevalence of ansa pancreatica is low, its presence can have great impact on the necessary approach for endoscopic therapy in chronic pancreatitis. In our case, the patient failed several ERCP attempts via ventral duct cannulation, and endoscopic therapy was successful only when cannulation of dorsal pancreatic duct was performed. In conclusion, in patients with chronic pancreatitis, recognition of ansa pancreatica, when present, is important to guide the endoscopic approach to treatment as minor papilla cannulation, a necessary skill for the interventional endoscopist, may be required.

1136-P: Chemical Pancreatectomy as a Revolutionary Therapy for Chronic Pancreatitis and Prevention of Type 3C Diabetes

Background: Chronic pancreatitis (CP) is a debilitating disease that leads to chronic pain, pancreatic endocrine and exocrine dysfunction. CP affects &amp;gt; 140,000 in the U.S. and millions worldwide. Type 3C diabetes, a brittle form of diabetes, constitutes 9% of those hospitalized with diabetes. Total pancreatectomy with auto islet cell transplantation (TPIAT) may treat CP and preserve endocrine function, but it is major surgery, the outcomes are variable, and islet yield is questionable. Methods: An intrapancreatic infusion of 150 µL of acetic acid or sham was performed on 8-week old CD1 mice. Serum enzymes, GTT, GSIS, behavioral pain assessment, histology and IHC were done 4 weeks and 8 weeks after surgery. Results: There was no significant difference between the two groups in serum amylase and lipase, GTT, GSIS, and pain parameters. IHC revealed negative staining for amylase and normal insulin staining while histology showed intact islets, replacement of acinar cells with fat cells, and no signs of inflammation. Conclusion: This procedure may be a revolutionary non-invasive therapy for CP able to relieve pain and preserve endocrine function. It may rescue ailing islets by removing the source of injury (exocrine tissue) without major surgery. The loss of the exocrine tissue is trivial because it is not functional, and most patients with CP require enzyme replacement therapy. Disclosure M. Saleh: None. R.S. Kalsi: None. G. Gittes: None.

Clinical course and approaches to the therapy of chronic pancreatitis in patients with comorbid pathology

The features of pathogenesis, clinical course and diagnostics of chronic pancreatitis combined with diseases of the cardiovascular system are discussed in the article. Results of the author’s own research on the effectiveness of influence of enzyme replacement therapy on the course of pancreatitis and comorbid pathology are presented. Significant positive dynamics of both manifestations of chronic pancreatitis and cardiovascular diseases, laboratory and instrumental examinations, improvement of patients’ quality of life upon the prescription of pancreatin are noted.

United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis (HaPanEU).

There have been substantial improvements in the management of chronic pancreatitis, leading to the publication of several national guidelines during recent years. In collaboration with United European Gastroenterology, the working group on 'Harmonizing diagnosis and treatment of chronic pancreatitis across Europe' (HaPanEU) developed these European guidelines using an evidence-based approach. Twelve multidisciplinary review groups performed systematic literature reviews to answer 101 predefined clinical questions. Recommendations were graded using the Grading of Recommendations Assessment, Development and Evaluation system and the answers were assessed by the entire group in a Delphi process online. The review groups presented their recommendations during the 2015 annual meeting of United European Gastroenterology. At this one-day, interactive conference, relevant remarks were voiced and overall agreement on each recommendation was quantified using plenary voting (Test and Evaluation Directorate). After a final round of adjustments based on these comments, a draft version was sent out to external reviewers. The 101 recommendations covered 12 topics related to the clinical management of chronic pancreatitis: aetiology (working party (WP)1), diagnosis of chronic pancreatitis with imaging (WP2 and WP3), diagnosis of pancreatic exocrine insufficiency (WP4), surgery in chronic pancreatitis (WP5), medical therapy (WP6), endoscopic therapy (WP7), treatment of pancreatic pseudocysts (WP8), pancreatic pain (WP9), nutrition and malnutrition (WP10), diabetes mellitus (WP11) and the natural course of the disease and quality of life (WP12). Using the Grading of Recommendations Assessment, Development and Evaluation system, 70 of the 101 (70%) recommendations were rated as 'strong' and plenary voting revealed 'strong agreement' for 99 (98%) recommendations. The 2016 HaPanEU/United European Gastroenterology guidelines provide evidence-based recommendations concerning key aspects of the medical and surgical management of chronic pancreatitis based on current available evidence. These recommendations should serve as a reference standard for existing management of the disease and as a guide for future clinical research.