Family History Of Chronic Pancreatitis Research Articles

Analysis of INSPPIRE-2 Cohort: Risk Factors and Disease Burden in Children With Acute Recurrent or Chronic Pancreatitis.

The objective of this study is to investigate risk factors and disease burden in pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). Data were obtained from INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2 (INSPPIRE-2), the largest multi-center prospective cohort study in pediatric patients with ARP or CP. Of 689 children, 365 had ARP (53%), 324 had CP (47%). CP was more commonly associated with female sex, younger age at first acute pancreatitis (AP) attack, Asian race, family history of CP, lower BMI%, genetic and obstructive factors, PRSS1 mutations and pancreas divisum. CFTR mutations, toxic-metabolic factors, medication use, hypertriglyceridemia, Crohn disease were more common in children with ARP. Constant or frequent abdominal pain, emergency room (ER) visits, hospitalizations, medical, endoscopic or surgical therapies were significantly more common in CP, episodic pain in ARP. A total of 33.1% of children with CP had exocrine pancreatic insufficiency (EPI), 8.7% had diabetes mellitus. Compared to boys, girls were more likely to report pain impacting socialization and school, medical therapies, cholecystectomy, but no increased opioid use. There was no difference in race, ethnicity, age at first AP episode, age at CP diagnosis, duration of disease, risk factors, prevalence of EPI or diabetes between boys and girls. Multivariate analysis revealed that family history of CP, constant pain, obstructive risk factors were predictors of CP. Children with family history of CP, constant pain, or obstructive risk factors should raise suspicion for CP.

Early-Onset Acute Recurrent and Chronic Pancreatitis Is Associated with PRSS1 or CTRC Gene Mutations

To assess whether the age of onset was associated with unique features or disease course in pediatric acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP). Demographic and clinical information on children with ARP or CP was collected at INSPPIRE (INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE) centers. The Cochran-Armitage trend test and Jonckheere-Terpstra test were used to examine for differences between pediatric age groups (<6, 6-11, and ≥12 years). Between September 2012 and March 2016, 342 children with ARP or CP were enrolled; 129 (38%) were <6 years of age at the time of first diagnosis of acute pancreatitis, 111 (32%) were 6-11 years of age, and 102 (30%) were ≥12 years of age. Early-onset disease was associated with mutations in cationic trypsinogen (PRSS1) (P < .01), chymotrypsin C (CTRC) (P = .01), family history of acute pancreatitis (P = .02), family history of CP (P < .01), biliary cysts (P = .04), or chronic renal failure (P = .02). Later-onset disease was more commonly present with hypertriglyceridemia (P = .04), ulcerative colitis (P = .02), autoimmune diseases (P < .0001), or medication use (P < .01). Children with later-onset disease also were more likely to visit the emergency department (P < .05) or have diabetes (P < .01). Early-onset pancreatitis is associated strongly with PRSS1 or CTRC mutations and family history of pancreatitis. Children with later-onset disease are more likely to have nongenetic risk factors. Future studies are needed to investigate whether the disease course, response to therapy, or clinical outcomes differ relative to the timing of disease onset.

Metabolic Syndrome, Insulin Resistance, Circadian Disruption, Antioxidants and Pancreatic Carcinoma: an Overview

The incidence and number of deaths caused by pancreatic tumours have been gradually rising, while the incidence and mortality of other common cancers have been declining. Risk factors for this malignant disease include cigarette smoking, family history of chronic pancreatitis, advancing age, male sex, diabetes mellitus, obesity, non-0 blood group, a high-fat diet, alcohol consumption and possibly Helicobacter pylori and hepatitis B virus infections. Metabolic diseases have become the leading cause of death in many countries. Our paper serves as a focused and updated discussion about the development of novel preventive strategies for this deadly disease.

Co-existence of CFTR and SPINK1 Gene Mutations in an Idiopathic Chronic Pancreatitis Case

Familial aggregation of CP suggests genetic factors for disease without definitive mode of inheritance. The hypothesized primary putative gene for CP includes SPINK1, CTSB, CTRC, PRSS1 and CFTR. These genes interact with each other and exhibit a variable phenotype in patients. The present report describes a male adult aged 42 years with a complaint of severe recurrent pain in the abdomen and weight loss and the age of onset was 35 years. The family history of chronic pancreatitis was not found. The biochemical examination revealed the exocrine insufficiency. Abdominal CT identified a dilated main pancreatic duct with numerous stones in the pancreas head. Genetic studies identified the patient to be heterozygous for p.N34S and G551D in SPINK1 and CFTR gene. Extended family screening identified his son (10 years) to have the both mutation p.N34S and G551D mutation in heterozygous state. Present findings suggest the need of genetic diagnosis in familial CP cases thereby precaution can be taken to delay or avoid the disease onset.

Family History of Chronic Pancreatitis Is Associated with an Increased Risk for Developing Chronic Pancreatitis

Purpose: Over the past 10 years there has been a growing recognition that hereditary factors are involved in the susceptibility to chronic pancreatitis (CP); however, the overall percentage of chronic pancreatitis that can be attributed as familial (defined as >2 or more first-degree relatives (FDR) with CP) is unknown. The aims of this study were to determine the proportion of CP patients with a family history (FH) of CP and the risk of CP development in FDR of probands referred to secondary and tertiary referral centers. Methods: The FH of CP from 540 CP patients (proband) and 504 unrelated controls prospectively recruited in the North American Pancreatitis Study-2 (NAPS2) dataset from 20 U.S. centers was analyzed. CP in the proband was defined by imaging or histology. CP in family members and controls was solely based on history obtained from the probands. To attempt to control for any recruitment bias, patients identified at enrollment to potentially have a genetic etiology for their CP by the patient or investigator were both excluded and included to calculate a minimum/maximum odds ratio and 95% CI. Results: See Table for breakdown of study population. Compared to controls, a CP patient was 2.3 (1.1–4.7) to 4.4 (2.3–8.2) times more likely to have at least one FDR with a history of CP. The risk for developing CP in a FDR of a CP versus a control patient was 2.5 (1.3–4.9) to 4.5 (2.5–8.2). Conclusion: 1) To the best of our knowledge this is the first report estimating the genetic contribution to chronic pancreatitis development. About 5–10% of cases in this large prospective cohort (22/413 or 52/540) could be considered familial. 2) There is approximately a 2.5 to 4.5-fold risk for a family member of a chronic pancreatitis patient to develop chronic pancreatitis. 3) Results from this study provide strong justification for identifying those genetic factors responsible for chronic pancreatis development and emphasize the importance of family history as a risk factor for chronic pancreatitis.Table: Study Population.

Reversal of elevated pancreatic enzymes after Helicobacter pylori eradication

Chronic pancreatitis is a syndrome involving progressive inflammatory changes in the pancreas that result in permanent structural damage, and ultimately impairment of exocrine and endocrine function [1]. In the last 2 years we observed five patients referred for possible chronic pancreatitis based on moderately elevated levels of serum amylase and lipase and abnormal ultrasonographic imaging (Table 1). Family history of chronic pancreatitis (hereditary pancreatitis) was negative and none of the patients were receiving drugs known to cause pancreatic damage. Cessation of alcohol intake and small meals low in fat was the only treatment undertaken from the patients. All patients had active H. pylori infection, with a histological diagnosis of chronic active gastritis, without peptic ulcer disease. Eradication treatment was given with omeprazole, tetracycline-HCL, metronidazole and colloidal bismuth subcitrate taken with the midday and evening meals for 10 days [2]. C-Urea Breath test was repeated 4–6 weeks after the end of treatment and all patients resulted cured. Serum pancreatic amylase and lipase levels were re-evaluated after 3, 6 and 10–12 months in two different laboratories and resulted persistently normal (Table 1). A potential role of H. pylori infection in several extraintestinal pathologies has been suggested [3] and a link between gastric infection by H. pylori and autoimmune pancreatitis has been hypothesized [4]. Interestingly, in a recent study, Helicobacter DNA was detected in pancreas, including tumor tissue and surrounding pancreas of 75% of patients with pancreatic cancer, and 60% of patients with chronic pancreatitis, suggesting a possible role of H. pylori in the development of chronic pancreatitis and pancreatic

Genetic risk factors in pancreatic diseases--significance for general practice

A genetic investigation is useful when there is evidence for a family history of chronic pancreatitis and, at absence of typical risk factors, in patients with onset of disease earlier than 35-40 years of age. In addition to alcohol abstinence the patients should be advised not to smoke. National and international registers as well as self-aid groups exist.

Analysis of the human pancreatic secretory trypsin inhibitor (PSTI) gene mutations in Japanese patients with chronic pancreatitis.

Chronic pancreatitis (CP) is a continuing or relapsing inflammatory disease of the pancreas. Several studies have demonstrated that mutations in the cationic trypsinogen (PRSS1) gene and the cystic fibrosis transmembrane conductance regulator (CFTR) gene are causative of the pathogenesis in a subset of hereditary and/or idiopathic CP cases. Recently, the N34S alteration of the pancreatic secretory trypsin inhibitor (PSTI) gene has been suggested to be closely associated with the pathogenesis of hereditary and/or idiopathic CP. Herein we analyzed genetic alterations of the PSTI gene in 32 unrelated Japanese CP patients who developed juvenile-onset CP or had a family history of CP; 5 patients were found to harbor alterations in this gene. In 3 of these 5 patients, heterozygous N34S alterations were found; this frequency is significantly lower than that in Caucasian patients reported previously. Moreover, a novel homozygous G-to-A transition in the promoter region of PSTI at 215bp upstream from the translation initiation site (-215G>A) was observed in 2 patients. We further surveyed the -215G>A alteration in 117 normal individuals; none of these individuals harbored this alteration. Our results suggested that the -215G>A alteration, as well as the N34S alteration, is a predisposing factor for CP.

A signal peptide cleavage site mutation in the cationic trypsinogen gene is strongly associated with chronic pancreatitis

Background & Aims: In pancreatitis, a key role has been attributed to the inappropriate conversion of trypsinogen to trypsin. Recently, two mutations of the cationic trypsinogen gene were found in families with hereditary pancreatitis. This study was conducted to determine the spectrum and frequency of cationic trypsinogen mutations in unrelated patients with idiopathic or hereditary chronic pancreatitis (CP). Methods: DNA samples from 44 unrelated children and adolescents with CP (30 patients with idiopathic CP and 14 with hereditary CP) and from 56 family members were investigated. The cationic trypsinogen gene was screened for mutations by single-strand conformation polymorphism analysis and DNA sequencing. Results: A mutation in the cationic trypsinogen gene was detected in 5 patients: in 2 patients with a family history of CP and in 3 patients with idiopathic CP. In 1 patient the formerly described R122H mutation was detected. In 4 patients a hitherto unknown mutation was found at the signal peptide cleavage site leading to an alanine to valine exchange in codon 16. The mutations were inherited in all cases. In 95 unrelated control individuals the A16V mutation was not found. Conclusions: Heterozygosity for the A16V mutation is strongly associated with CP. These results indicate that a significant percentage of patients with idiopathic CP may have a genetic basis for their disorder; therefore, genetic testing should be included in the diagnostic evaluation of these patients. GASTROENTEROLOGY 1999;117:7-10