Alcohol-induced Chronic Pancreatitis Research Articles

Causal link between gut microbiota and four types of pancreatitis: a genetic association and bidirectional Mendelian randomization study

BackgroundA number of recent observational studies have indicated a correlation between the constitution of gut microbiota and the incidence of pancreatitis. Notwithstanding, observational studies are unreliable for inferring causality because of their susceptibility to confounding, bias, and reverse causality, the causal relationship between specific gut microbiota and pancreatitis is still unclear. Therefore, our study aimed to investigate the causal relationship between gut microbiota and four types of pancreatitis.MethodsAn investigative undertaking encompassing a genome-wide association study (GWAS) comprising 18,340 participants was undertaken with the aim of discerning genetic instrumental variables that exhibit associations with gut microbiota, The aggregated statistical data pertaining to acute pancreatitis (AP), alcohol-induced AP (AAP), chronic pancreatitis (CP), and alcohol-induced CP (ACP) were acquired from the FinnGen Consortium. The two-sample bidirectional Mendelian randomization (MR) approach was utilized. Utilizing the Inverse-Variance Weighted (IVW) technique as the cornerstone of our primary analysis. The Bonferroni analysis was used to correct for multiple testing, In addition, a number of sensitivity analysis methodologies, comprising the MR-Egger intercept test, the Cochran’s Q test, MR polymorphism residual and outlier (MR-PRESSO) test, and the leave-one-out test, were performed to evaluate the robustness of our findings.ResultsA total of 28 intestinal microflora were ascertained to exhibit significant associations with diverse outcomes of pancreatitis. Among them, Class Melainabacteria (OR = 1.801, 95% CI: 1.288–2.519, p = 0.008) has a strong causality with ACP after the Bonferroni-corrected test, in order to assess potential reverse causation effects, we used four types of pancreatitis as the exposure variable and scrutinized its impact on gut microbiota as the outcome variable, this analysis revealed associations between pancreatitis and 30 distinct types of gut microflora. The implementation of Cochran’s Q test revealed a lack of substantial heterogeneity among the various single nucleotide polymorphisms (SNP).ConclusionOur first systematic Mendelian randomization analysis provides evidence that multiple gut microbiota taxa may be causally associated with four types of pancreatitis disease. This discovery may contribute significant biomarkers conducive to the preliminary, non-invasive identification of Pancreatitis. Additionally, it could present viable targets for potential therapeutic interventions in the disease’s treatment.

The hidden dangers of chronic pancreatitis in pregnancy: Evidence from a large-scale population study

BackgroundChronic pancreatitis is a debilitating condition that can affect women of childbearing age, and its impact on maternal and perinatal outcomes is poorly understood. AimsOur findings aim to help healthcare providers counsel pregnant women with chronic pancreatitis and make informed clinical decisions. MethodsIn this study, hospital discharge records from the National Inpatient Sample database between 2009 and 2019 were retrospectively analyzed to investigate maternal primary outcomes and primary perinatal outcomes. ResultsThe study findings suggest an association between chronic pancreatitis and elevated rates of gestational diabetes (AOR 1.63, 95% CI 1.19–2.23) and gestational hypertensive complications(AOR 2.48, 95% CI 1.87–3.29). Pregnancies among women with chronic pancreatitis showed an increased likelihood of preterm labor (AOR 3.10, 95% CI 2.40–4.00) and small for gestational age (AOR 2.40, 95% CI 1.35–3.08). Furthermore, it appears that patients with alcohol-induced chronic pancreatitis present a considerably higher risk of fetal death (OR 17.15, 95% CI 2.29–128.26). The study also revealed that those chronic pancreatitis patients with a history of chronic renal failure could be more prone to developing gestational hypertensive complications (OR 20.09, 95%CI 2.07–194.93). Moreover, associations were observed between chronic pancreatitis pregnancies and lengthier hospital stays as well as elevated hospital costs. ConclusionsOur research has uncovered a heightened risk of complications associated with chronic pancreatitis for mothers and fetuses. The implications of our findings are critical for healthcare professionals, particularly those involved in preconception counseling.

Physicochemical properties of blood and urine in patients with alcohol-induced chronic pancreatitis against the background of obesity

In this article, the authors present the results of their studies of the physicochemical properties of blood and urine in patients with chronic alcohol-induced pancreatitis (CAP) combined with obesity.
 110 patients with CAP in the acute stage against the background of obesity were examined. The ages of the examined patients ranged from 23 to 60. There were 77 (70.0%) men and 33 (30.0%) women among the patients. We also examined 30 almost healthy people aged 20 to 60 (the control group).
 There are significant changes in the physicochemical properties of blood and urine in patients with CAP against the background of obesity. Indices of interfacial tensiometry and rheometry of these biological fluids correlate with other clinical, laboratory, and instrumental data in patients with CAP combined with obesity. This allows us to recommend the assessment of dynamic surface tension and rheometric indices of blood and urine for screening and an integral assessment of the functional state of the pancreas in comorbidity. In addition, it is reasonable to use the results of interfacial tensiometry and rheometry for screening the metabolic syndrome in patients with CAP against the background of obesity. In the metabolic syndrome, there is a significant increase in the surface tension 3 of the blood; in the absence of this syndrome, on the contrary, the surface tension 3 of the blood is significantly reduced.
 In patients with biliary sludge and cholelithiasis, the blood viscoelasticity index (E) was significantly lower (23.18±1.07 mN/m), while without concomitant diseases of the biliary tract, the blood E was equal to 27.84±1.08 mN/m (p<0.05). Both with and without changes in the biliary system, blood E in patients with CAP against the background of obesity was significantly lower than in the control group.
 The prospects of research are to study the dynamics of tensiometry and rheometry of biological fluids in CAP combined with obesity under the influence of treatment in order to study the possibility of using these indices in the integrated assessment of the effectiveness of therapy.

Causal associations between modifiable risk factors and pancreatitis: A comprehensive Mendelian randomization study.

The pathogenesis of pancreatitis involves diverse environmental risk factors, some of which have not yet been clearly elucidated. This study systematically investigated the causal effects of genetically predicted modifiable risk factors on pancreatitis using the Mendelian randomization (MR) approach. Genetic variants associated with 30 exposure factors were obtained from genome-wide association studies. Summary-level statistical data for acute pancreatitis (AP), chronic pancreatitis (CP), alcohol-induced AP (AAP) and alcohol-induced CP (ACP) were obtained from FinnGen consortia. Univariable and multivariable MR analyses were performed to identify causal risk factors for pancreatitis. Genetic predisposition to smoking (OR = 1.314, P = 0.021), cholelithiasis (OR = 1.365, P = 1.307E-19) and inflammatory bowel disease (IBD) (OR = 1.063, P = 0.008) as well as higher triglycerides (OR = 1.189, P = 0.016), body mass index (BMI) (OR = 1.335, P = 3.077E-04), whole body fat mass (OR = 1.291, P = 0.004) and waist circumference (OR = 1.466, P = 0.011) were associated with increased risk of AP. The effect of obesity traits on AP was attenuated after correcting for cholelithiasis. Genetically-driven smoking (OR = 1.595, P = 0.005), alcohol consumption (OR = 3.142, P = 0.020), cholelithiasis (OR = 1.180, P = 0.001), autoimmune diseases (OR = 1.123, P = 0.008), IBD (OR = 1.066, P = 0.042), type 2 diabetes (OR = 1.121, P = 0.029), and higher serum calcium (OR = 1.933, P = 0.018), triglycerides (OR = 1.222, P = 0.021) and waist-to-hip ratio (OR = 1.632, P = 0.023) increased the risk of CP. Cholelithiasis, triglycerides and the waist-to-hip ratio remained significant predictors in the multivariable MR. Genetically predicted alcohol drinking was associated with increased risk of AAP (OR = 15.045, P = 0.001) and ACP (OR = 6.042, P = 0.014). After adjustment of alcohol drinking, genetic liability to IBD had a similar significant causal effect on AAP (OR = 1.137, P = 0.049), while testosterone (OR = 0.270, P = 0.002) a triglyceride (OR = 1.610, P = 0.001) and hip circumference (OR = 0.648, P = 0.040) were significantly associated with ACP. Genetically predicted higher education and household income levels could lower the risk of pancreatitis. This MR study provides evidence of complex causal associations between modifiable risk factors and pancreatitis. These findings provide new insights into potential therapeutic and prevention strategies.

Association between Dietary Habits and Pancreatitis among Individuals of European Ancestry: A Two-Sample Mendelian Randomization Study

Dietary factors are believed to potentially influence the risk of pancreatitis. Here, we systematically investigated the causal relationships between dietary habits and pancreatitis by using two-sample Mendelian randomization (MR). Large-scale genome-wide association study (GWAS) summary statistics for dietary habits were obtained from the UK Biobank. GWAS data for acute pancreatitis (AP), chronic pancreatitis (CP), alcohol-induced AP (AAP) and alcohol-induced CP (ACP) were from the FinnGen consortium. We performed univariable and multivariable MR analyses to evaluate the causal association between dietary habits and pancreatitis. Genetically driven alcohol drinking was associated with increased odds of AP, CP, AAP and ACP (all with p < 0.05). Genetic predisposition to higher dried fruit intake was associated with reduced risk of AP (OR = 0.280, p = 1.909 × 10-5) and CP (OR = 0.361, p = 0.009), while genetic predisposition to fresh fruit intake was associated with reduced risk of AP (OR = 0.448, p = 0.034) and ACP (OR = 0.262, p = 0.045). Genetically predicted higher consumption of pork (OR = 5.618, p = 0.022) or processed meat (OR = 2.771, p = 0.007) had a significant causal association with AP, and genetically predicted higher processed meat intake increased the risk of CP (OR = 2.463, p = 0.043). Our MR study showed that fruit intake may be protective against pancreatitis, whereas dietary intake of processed meat has potential adverse impacts. These findings may inform prevention strategies and interventions directed toward dietary habits and pancreatitis.

Orbital Lipolysis.

HomeRadiologyVol. 307, No. 2 PreviousNext Reviews and CommentaryFree AccessImages in RadiologyOrbital LipolysisTuba Kalelioglu , Sohil H. PatelTuba Kalelioglu , Sohil H. PatelAuthor AffiliationsFrom the Department of Radiology and Medical Imaging, University of Virginia Health System, 1215 Lee St, 1st Floor, Charlottesville, VA 22903.Address correspondence to T.K. (email: [email protected]).Tuba Kalelioglu Sohil H. PatelPublished Online:Jan 24 2023https://doi.org/10.1148/radiol.221947MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In A 47-year-old man with a history of squamous cell carcinoma of the oral tongue, alcohol-induced chronic pancreatitis with gastrostomy tube dependence, and chronic diarrhea presented to the emergency department with altered mental status. The patient was cachectic, with a body mass index of 14.3 kg/m2.MRI of the brain demonstrated diffuse loss of expected fat signal intensity with T1-weighted imaging, including within the orbits, bone marrow, and subcutaneous scalp (Figure). This appearance is similar to a fat-saturated T1-weighted image; hence, it is called “pseudo fat-saturated” (1). It is due to excessive lipolysis and lipid peroxidation induced by cachexia from chronic malnutrition in the setting of anorexia nervosa or systemic cancer. Furthermore, endothelial injury results in edema and contrast enhancement in the involved areas, conspicuous in the postseptal orbit (2).Images in a 47-year-old man with cachectic state. (A) T1-weighted image before cachectic state for comparison shows expected normal high signal intensity of the orbital, scalp, and bone marrow fat. (B) Axial T1-weighted image without fat suppression shows lack of expected hyperintense fat in the orbits, subcutaneous scalp, and bone marrow. The imaging appearance mimics a fat-saturated T1-weighted image. The volume of subcutaneous fat in temporal regions is decreased. (C) Postcontrast T1-weighted image shows diffuse contrast enhancement of the affected areas secondary to increased vessel wall permeability. (D) Noncontrast CT scan shows increased attenuation in the retrobulbar fat, consistent with edema.Download as PowerPointOpen in Image Viewer Disclosures of conflicts of interest: T.K. No relevant relationships. S.H.P. No relevant relationships.

S1549 An Ominous Connection Causing Recurrent Pleural Effusions

Introduction: Fistulation is a rare complication of chronic pancreatitis. Pancreaticopleural fistula (PPF) typically presents with thoracic symptoms. Pathogenesis is related to pancreatic duct obstruction causing leakage of pancreatic fluid, and if persistent can lead to fistula formation. Due to its predominant thoracic over abdominal symptoms, the diagnosis and treatment of PPF are usually delayed. The following case is an example of the potential need for repeat testing to confirm the diagnosis of PPF as well as a multidisciplinary approach to treatment. Case Description/Methods: A 66-year-old white woman presented to the emergency department with 10 days history of worsening dyspnea, orthopnea, and chest tightness. Her medical history was notable for alcohol-induced chronic pancreatitis. On physical examination, she was tachycardic with diminished breath sounds bilaterally. Chest CT angiogram revealed bilateral pleural effusions. Diagnostic right sided thoracentesis revealed exudative fluid pattern, but negative for infection and malignancy. Symptoms initially improved after therapeutic thoracentesis, but pleural effusions shortly recurred requiring repeat thoracenteses. Pleural effusions laboratory findings on thoracenteses are listed in Tables 1 and 2. MRCP showed an irregular tubular tract extending cephalad from the pancreas toward the right diaphragmatic crus and appeared to communicate with the right hydropneumothorax (Figure 1). ERCP was performed which showed diffuse dilatation of the pancreatic duct (Figure 2). Patient underwent therapeutic stenting to the ventral pancreatic duct (Figure 3). She had complete resolution of symptoms and pleural effusions on 2 months follow-up chest CT. Discussion: Pancreatic pleural fistula is a rare complication of chronic pancreatitis and can be a challenging diagnosis as symptoms tend to overlap with other causes of dyspnea, hypoxia and pleural effusions. MRCP is the most sensitive imaging modality, followed by ERCP and CT to visualize pancreatic duct anatomy and guide further therapeutic management. Conservative medical management with bowel rest and somatostatin analog are shown to be effective in patients without pancreatic ductal obstructions. In cases with recurrent pleural effusions despite conservative management, ERCP with therapeutic stenting to alleviate pancreatic ductal obstructions is strongly indicated with high success rate. Owing to its rarity and complexity, a multidisciplinary approach to PPF is warranted to provide the best care possible.Figure 1.: Tables and Figures.

Glycogenic Hepatopathy in a Patient with Pancreatogenic Diabetes

Glycogenic hepatopathy is characterized by acute liver injury secondary to reversible accumulation of excess glycogen in hepatocytes. This phenomenon has been described in type 1 diabetes, with few cases reported in patients with type 2 diabetes. Glycogenic hepatopathy in the setting of pancreatogenic (type 3c) diabetes has yet to be reported.A 57-year-old female with a history of insulin-requiring pancreatogenic diabetes mellitus secondary to alcohol-induced chronic pancreatitis status post distal pancreatectomy presented with recurrent admissions for abdominal pain, hyperglycemia, hyperosmolar hyperglycemic state (HHS), and unexplained elevation of liver transaminase levels. Glycemic control remained poor over many years with consistently elevated HbA1c in the setting of labile blood sugars, medication noncompliance, and lifestyle non-adherence.The patient was admitted to the hospital with altered mental status and markedly elevated blood glucose (1,182 mg/dL) concerning for HHS. On admission, her liver function tests (LFTs) revealed elevated alkaline phosphatase (1,011 U/L, n <150 U/L), AST (583 U/L, n <34 U/L), and ALT (517 U/L, n <55 U/L). Direct and total bilirubin were within normal limits. The patient underwent extensive workup including drug and toxin levels, autoimmune evaluation, serology for infectious causes, abdominal computed tomography scanning, right upper quadrant ultrasound, and magnetic resonance cholangiopancreatography (MRCP). All laboratory workup was negative, ultrasound was unremarkable, and MRCP showed no evidence of biliary or common bile duct dilatation. Throughout her hospitalization, LFTs gradually improved with optimization of blood glucose.Less than one week later, the patient returned with blood glucose of 673 mg/dL and LFTs notable for alkaline phosphatase 789 U/L, AST 1,068 U/L, and ALT 299 U/L. Again, all testing was negative for causes of rapid increase in liver enzymes. Similar to previous admissions, her LFTs improved with resolution of hyperglycemia. Review of electronic medical record revealed a similar trend during previous admissions. The patient did not undergo liver biopsy; however, the parallel relationship of LFTs and hyperglycemia, in the absence of radiologic or laboratory evidence of alternate liver pathology, supports the diagnosis of glycogenic hepatopathy.This is the first case of glycogenic hepatopathy reported in a patient with pancreatogenic diabetes. Due to the rarity of this condition and minimal literature of its occurrence in adult non-type-1 diabetics, glycogenic hepatopathy is likely infrequently considered when evaluating patients with recurrent hyperglycemia and elevated LFTs. This case accentuates the need for further research of this condition in non-type 1 diabetics as the prognosis and management differ from other forms of acute liver injury.

Clinicopathological features of Pseudocyst Pancreas and its Management: A Prospective and Retrospective Study

Background: Revised Atlanta Classification has veered a change in our understanding ofpseudocyst pancreas which mandates renewed inquiry into pseudocysts defined as per new criteria.The present study provides an overview of experience with Pseudocyst Pancreas for over a decade.Methodology: 100 cases of pseudocysts diagnosed over the last 10 years at GMC, Bhopal,conforming to the present definition were reviewed. Cysts with the inhomogeneous collection,debris, necrosis, or any other non-liquid component, specifically in those diagnosed before 2012were excluded. Relevant data were analyzed. Results: The majority were male (85%) in the agegroup of 40-50 years with alcohol-induced chronic pancreatitis (77%) being the most frequentetiology. Abdominal pain (40%), lump (30%), and abdominal tenderness (59%) were common atpresentation. 58% were in the Head of the pancreas, 29% in the Neck and Body, and 13% in theTail and surrounding areas. Mean cyst diameter was 8.6cm and volume 252cc. 85% were managedsurgically and 40% of those managed conservatively also needed surgical intervention eventuallydue to complications. History of chronic alcoholic pancreatitis, the large size of the cyst (≥6cm and≥60cc), and communication with the main pancreatic duct were highly predictive of surgicalintervention. Conclusion: Radiological characteristics along with the clinical picture may suggestappropriate intervention. Surgery remains the principal modality of treatment, with high successrates.

A high prevalence of genetic polymorphisms in idiopathic and alcohol-associated chronic pancreatitis patients in Ireland

BackgroundIndividual genetic architecture is considered central to susceptibility and progression of disease in chronic pancreatitis. The study aimed to evaluate the presence of common pancreatic gene mutations in a defined cohort of idiopathic and alcohol-induced chronic pancreatitis patients in Ireland. MethodsThe study comprised patients with idiopathic and alcohol-induced chronic pancreatitis and historic controls. Variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, cationic trypsinogen (PRSS1) gene and serine protease inhibitor kazal type-1 (SPINK1) gene, were assessed by Taqman© genotyping assay. ResultsOf n = 126 patients and n = 167 controls, mutations were detected in 23 (20%) and in 10 (6%) respectively (P < 0.001). The majority of mutations found were in the SPINK1 gene variant N34S (13%) which increased disease risk almost six-fold (OR 5.9). Neither CFTR severe mutation (F508del) (P = 0.649) nor mild variant (R117H) (P = 0.327) were over-represented amongst patients compared to control subjects. PRSS1 variants were not detected in either patient or control subjects. ConclusionThere was a significant prevalence of chronic pancreatitis-associated gene mutations in this well-phenotyped cohort. In patients with alcohol-related or idiopathic chronic pancreatitis, the possibility of genetic mutations in the SPINK 1 gene should be considered as a contributing aetiology factor.

Correlation of Pancreatic T1 Values Using Modified Look-Locker Inversion Recovery Sequence (MOLLI) with Pancreatic Exocrine and Endocrine Function.

Quantifying myocardial T1 values has been useful for detecting and characterizing fibrotic appearance in myocardial infarction, focal scars, and non-ischemic cardiomyopathies. Since pancreatic exocrine function decreases with chronic pancreatic fibrosis advancement, this study examined the correlation between pancreatic T1 values and pancreatic exocrine and endocrine insufficiency. Methods: Thirty-two patients underwent abdominal contrast-enhanced MRI in our department between October 2017 and February 2019. We evaluated the T1 values of the pancreas using a modified Look-Locker inversion recovery sequence (MOLLI), pancreatic exocrine insufficiency (PEI) by fecal elastase 1 (FE1) values, and pancreatic endocrine insufficiency using fasting insulin and blood glucose levels to calculate the HOMA-β. This trial is registered in the UMIN Clinical Trials Registry as UMIN 000030067. Results: The median cohort (9 males and 23 females) age was 71 (range: 49–84) years. Eighteen patients had pancreatic cysts, three had alcohol-induced chronic pancreatitis, three had pancreatic cancer, and eight possessed other pancreatic features (two patients each with autoimmune pancreatitis, acute pancreatitis, or a bile duct tumor, one with idiopathic chronic pancreatitis, and one healthy control with negative findings). The median pancreatic T1 value measured by the MOLLI was 857.5 ms (597–2569). A significant negative correlation was found between the T1 mapping and FE1 values (r = 0.69, p < 0.01), with none for the T1 with HOMA-β or serum albumin, triglycerides, or body mass index. Conclusions: the pancreatic T1 values correlated significantly with pancreatic exocrine function and might be useful in PEI diagnosis.

SUN-912 The Rare Men of Mississippi Complications in the Diagnosis of Multiple Endocrine Neoplasia Type 1

Background: Multiple endocrine neoplasia type 1 (MEN1) is a rare, autosomal dominant disorder associated with tumors of the parathyroid glands, pituitary gland, and gastroenteropancreatic cells caused by mutations of the MEN1 tumor-suppressor gene. Thescarcity with which this syndrome is encountered makes diagnosis challenging in rural settings. Clinical Case: A 34-year-old male presented to the Emergency Department complaining ofintermittent abdominal pain for the past year, that was associated with nausea, vomiting, and diarrhea. Past medical history was significant for hyperparathyroidism treated with parathyroidectomy, nephrolithiasis, and alcohol-induced chronic pancreatitis. Initial laboratory studies revealed elevated corrected calcium (11.5 mg/dL, n:7.6-10.6 mg/dL) with a subsequent elevated parathyroid hormone level (105, n:14-72 pg/mL). CT scan of the abdomen and pelvis revealed fatty liver changes, nonobstructive nephrolithiasis and pancreatic calcifications. Due to his recurrent symptoms, gastroenterology was consulted for esophagogastroduodenoscopy that revealed erosive esophagitis with multiple duodenal ulcers. The patient was started on a high dose Proton Pump Inhibitor IV and treated supportively. His symptoms improved within a few days. Additional studies were obtained including a gastrin level and H. pylori antigen testing that required sending out to an outside laboratory for analysis. He was discharged with close outpatient follow up scheduled, but then was readmitted two days later with recurrent symptoms. The patient was again treated with supportive care, and was able to provide additional family history revealing parathyroid and ulcer disease in both his father and paternal grandmother, which triggered suspicion for multiple endocrine neoplasia type 1. His gastrin level returned, and was found to be elevated (489 pg/mL, n < 100) with a negative H. pylori antigen, supporting the diagnosis of MEN1. Further diagnostic testing was performed, revealing an elevated serum chromogranin A level (117 ng/mL, n < 15) and abnormalities on MEN1 genetic testing. An Octreotide scan was then performed, showing a single intense area of uptake near the caudate lobe of liver. At this time, he was transferred to a tertiary medical center for further evaluation and management. Conclusion: This case illustrates the significance of suspicion for multiple endocrine neoplasia and the value of a complete history. Additionally, while a serum chromogranin A level can be nonspecific, it can be obtained in an outpatient setting to help differentiate neuroendocrine pathology from other etiologies. Though the symptoms of MEN1 patients can mimic many other disease processes, recognition of symptoms is critical for medical communities to provide swift treatment.

A high prevalence of genetic polymorphisms in idiopathic and alcohol-associated chronic pancreatitis patients in Ireland

Background: Rare pathogenic variants in serine protease inhibitor Kazal type-1 (SPINK1), cationic trypsinogen (PRSS1), cystic fibrosis transmembrane conductance regulator (CFTR) genes are strongly associated with the development and progression of chronic pancreatitis (CP), but are not routinely tested. For a considerable number of CP patients, the cause of disease is unknown or ambiguous despite sophisticated imaging and biochemical investigations. We hypothesised that some patients diagnosed with idiopathic or alcohol-induced CP may carry CP-related mutations. Therefore, we investigated the presence of CP-related gene mutations in idiopathic and alcohol-associated CP patients, compared to controls. Methods: 126 patients with idiopathic and alcohol-induced CP and 167 controls were enrolled following ethical approval. Mutations were assessed by Taqman© genotyping assay. The study was further reinforced by post hoc analysis of SPINK1 N34S with additional controls (total n=508). Results: Mutations were detected in 25 patients (19.8%) and 10 controls (6%)(P<0.001). The presence of a gene mutation increased disease risk three-fold (odds ratio (OR) 3.4). The majority of mutations were found in SPINK1 N34S (12.7%), which increased disease risk six-fold (OR 5.9). CFTR severe mutation (F508del) was present equally in patients and controls (P=0.746). CFTR mild variant (R117H) was not significantly represented amongst patients (P=0.169). PRSS1 variants were not detected in either group. SPINK1 N34S mutations were more common in patients (12.7%) than in controls (2.4% of n=508)(P=5*10-7). Conclusion: 20% of CP patients carried disease-associated / disease-modifying gene mutations, with SPINK1 N34S disease-altering mutation being unexpectedly high. We therefore suggest that the presence of a SPINK1 mutation should be considered in patients with idiopathic or alcohol-induced CP, particularly where diagnosis is uncertain. Early identification of the presence of variants will allow for modification of risk factors and improve CP management. Furthermore, identifying underlying heritable risk factors may contribute to improved options for disease prevention and treatment.

Spatial analysis of alcohol-related mortality in Slovakia.

The aim of our study was to investigate the relationship between alcohol-related mortality in Slovak regions, as represented by Nomenclature of Territorial Units for Statistics (NUTS) III level. We used data from mortality reports spanning 1996-2017 in the Slovak Republic. Data was provided by the National Health Information Centre in Slovakia. We applied two-dimensional correspondence analysis where the dimensions are regions and selected alcohol-related deaths diagnoses are classified by the International Classification of Diseases. Analysis revealed a relationship between the Prešov region and diagnoses I42 - Cardiomyopathy and K29 - Alcoholic gastritis. Furthermore, the Banská Bystrica and Žilina regions correspond to G31 - Degeneration of nervous system due to alcohol and K86 - Alcohol-induced chronic pancreatitis. In the case of K70 - Alcoholic liver disease - the Banská Bystrica, Trenčín and Nitra regions are identified as regions which have an intermediate relationship with this diagnosis. The Trnava region corresponds to F10 - Acute alcohol intoxication. The Trenčín and Nitra regions correspond closely to G62 - Alcoholic polyneuropathy. Perfect correspondence can be seen between the Košice region and K73 - Chronic hepatitis, not elsewhere classified. K74 - Fibrosis and cirrhosis of liver diagnosis also corresponds with the Košice region. The results of this analysis provide valuable insights for national and regional health policymakers in the process of preparing high-quality health regional plans, as well as retrospectively assessing the success of existing health policies and interventions in this area. Facts presented in the study justify the need for specialised health care, which is part of the process of building an Integrated Health Care Centre in Slovakia.

Chronic pancreatitis and the heart disease: Still terra incognita?

BACKGROUNDIt has been suggested that chronic pancreatitis (CP) may be an independent risk factor for development of cardiovascular disease (CVD). At the same time, it seems that congestive heart failure (CHF) and CP share the responsibility for the development of important clinical conditions such as sarcopenia, cachexia and malnutrition due to development of cardiac cachexia and pancreatic exocrine insufficiency (PEI), respectively.AIMTo explore the evidence regarding the association of CP and heart disease, more specifically CVD and CHF.METHODSA systematic search of MEDLINE, Web of Science and Google Scholar was performed by two independent investigators to identify eligible studies where the connection between CP and CVD was investigated. The search was limited to articles in the English language. The last search was run on the 1st of May 2019. The primary outcomes were: (1) Incidence of cardiovascular event [acute coronary syndrome (ACS), chronic coronary disease, peripheral arterial lesions] in patients with established CP; and (2) Incidence of PEI in patients with CHF.RESULTSOut of 1166 studies, only 8 were eligible for this review. Studies regarding PEI and CHF showed an important incidence of PEI as well as associated malabsorption of nutritional markers (vitamin D, selenium, phosphorus, zinc, folic acid, and prealbumin) in patients with CHF. However, after substitution of pancreatic enzymes, it seems that, at least, loss of appetite was attenuated. On the other side, studies investigating cardiovascular events in patients with CP showed that, in CP cohort, there was a 2.5-fold higher incidence of ACS. In another study, patients with alcohol–induced CP with concomitant type 3c diabetes had statistically significant higher incidence of carotid atherosclerotic plaques in comparison to patients with diabetes mellitus of other etiologies. Earlier studies demonstrated a marked correlation between the clinical symptoms in CP and chronic coronary insufficiency. Also, statistically significant higher incidence of arterial lesions was found in patients with CP compared to the control group with the same risk factors for atherosclerosis (hypertension, smoking, dyslipidemia). Moreover, one recent study showed that PEI is significantly associated with the risk of cardiovascular events in patients with CP.CONCLUSIONCurrent evidence implicates a possible association between PEI and malnutrition in patients with CHF. Chronic pancreatic tissue hypoxic injury driven by prolonged splanchnic hypoperfusion is likely to contribute to malnutrition and cachexia in patients with CHF. On the other hand, CP and PEI seem to be an independent risk factor associated with an increased risk of cardiovascular events.

A difficult-to-treat case of pancreas divisum complicated by pancreatic pseudocyst

A 45-year-old male drinker, who was hospitalized for alcohol-induced acute pancreatitis 7 years ago, recently visited us after a day-long abdominal pain and vomiting. He was hospitalized for acutely-aggravated alcohol-induced chronic pancreatitis, with increased biliary pancreatic enzyme, increased concentration of peripancreatic adipose tissue and pancreatic pseudocyst found by abdominal CT. Pancreatic enzyme decreased by conservative treatment. We performed ERCP (10th day) and diagnosed pancreas divisum with cauda equina-like Wirsung duct by major-papilla imaging. As accessory pancreatic duct imaging from minor-papilla was difficult due to excessive inflammation, we reperformed ERCP (23rd day) . ENPD was placed because cystic lesion connecting with Santolini duct was found by minor-papilla imaging. After smaller pancreatic cyst was found by CT, pancreatic duct stent was placed (31st day) , and the patient was discharged. We report a case of pancreas divisum complicated by pancreatic pseudocyst.

Hospital discharges and patient activity associated with chronic pancreatitis in Ireland 2009–2013

ObjectiveTo investigate trends in acute public hospital patient discharges in Ireland, to analyse hospital discharge activity for geographical variations, aetiological differences, and to estimate a national prevalence for chronic pancreatitis. MethodWe performed a nationwide retrospective study of all in-patient discharges from acute public hospitals in Ireland, participating in the Hospital In-Patient Enquiry (HIPE) reporting system. We searched for International Classification of Disease, Tenth Revision, Australian Modification (ICD-10-AM) codes K86.0 alcohol-induced chronic pancreatitis, and K86.1 other chronic pancreatitis, and data were extracted for the years 2009–2013. ResultsThere were 4098 emergency admissions for any aetiology chronic pancreatitis during the 5 year study period. Total discharges ranged from 753 in 2009 to 999 in 2013. Total patients ranged from 530 in 2009 to 601 in 2013. Prevalence of chronic pancreatitis is estimated at 11.6 per 100,000 to 13.0 per 100,000 over the five years. ‘Other aetiology chronic pancreatitis’ discharges were almost double that of ‘alcohol chronic pancreatitis’. We found notable geographical variation in hospital discharge activity for chronic pancreatitis. ConclusionsWe report a prevalence which is similar to those worldwide studies who adopted a similar methodology utilising exact counts of patients. Our data are an underestimated as they are based on in-patient discharges only, excluding those attending primary care, outpatient or emergency room visits without admission. Despite studying this disease in a population with high per capita alcohol consumption, we report almost twice as many discharges for non-alcohol aetiology chronic pancreatitis.

Pancreatic Pseudocyst Pleural Fistula in Gallstone Pancreatitis.

Extra-abdominal complications of pancreatitis such as pancreaticopleural fistulae are rare. A pancreaticopleural fistula occurs when inflammation of the pancreas and pancreatic ductal disruption lead to leakage of secretions through a fistulous tract into the thorax. The underlying aetiology in the majority of cases is alcohol-induced chronic pancreatitis. The diagnosis is often delayed given that the majority of patients present with pulmonary symptoms and frequently have large, persistent pleural effusions. The diagnosis is confirmed through imaging and the detection of significantly elevated amylase levels in the pleural exudate. Treatment options include somatostatin analogues, thoracocentesis, endoscopic retrograde cholangiopancreatography (ERCP) with pancreatic duct stenting, and surgery. The authors present a case of pancreatic pseudocyst pleural fistula in a woman with gallstone pancreatitis presenting with recurrent pneumonias and bilateral pleural effusions.

Genetic susceptibility factors for alcohol-induced chronic pancreatitis.

Chronic pancreatitis is a progressive inflammatory disease of the pancreas and frequently associated with immoderate alcohol consumption. Since only a small proportion of alcoholics eventually develop chronic pancreatitis genetic susceptibility factors have long been suspected to contribute to the pathogenesis of the disease. Smaller studies in ethnically defined populations have found that not only polymorphism in proteins involved in the metabolism of ethanol, such as Alcohol Dehydrogenase and Aldehyde Dehydrogenase, can confer a risk for developing chronic pancreatitis but also mutations that had previously been reported in association with idiopathic pancreatitis, such as SPINK1 mutations. In a much broader approach employing genome wide search strategies the NAPS study found that polymorphisms in the Trypsin locus (PRSS1 rs10273639), and the Claudin 2 locus (CLDN2-RIPPLY1-MORC4 locus rs7057398 and rs12688220) confer an increased risk of developing alcohol-induced pancreatitis. These results from North America have now been confirmed by a European consortium. In another genome wide approach polymorphisms in the genes encoding Fucosyltransferase 2 (FUT2) non-secretor status and blood group B were not only found in association with higher serum lipase levels in healthy volunteers but also to more than double the risk for developing alcohol-associated chronic pancreatitis. These novel genetic associations will allow to investigate the pathophysiological and biochemical basis of alcohol-induced chronic pancreatitis on a cellular level and in much more detail than previously possible.

Pancreatic actinomycosis: Possible complication of long-term pancreatic stenting, diagnosed on endoscopic retrograde cholangiopancreatography guided pancreatic duct brushings

AbstractEndoscopic ultrasound guided fine needle aspiration and endoscopic retrograde cholangiopancreatography guided biliary and pancreatic ductal brushings are being used as routine procedures to diagnose mass lesions of the pancreas and stenotic lesions of the biliary ducts and pancreas. We report a rare case of pancreatic actinomycosis in a patient with alcohol-induced chronic pancreatitis with biliary and pancreatic duct strictures and occluded pancreatic stents, diagnosed on pancreatic duct brushings.