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Background & Aims Idiopathic chronic pancreatitis (ICP) is the second most common subtype of CP. In 1994, researchers reported the bimodal age at onset of ICP symptoms: early onset ICP (EO-ICP; median age, 19.2 y) and late-onset ICP (LO-ICP; median age, 56.2 y). Ages of onset and clinical features of ICP differed from those of alcohol-related CP (ACP). However, variants in PRSS1 had not yet been associated with ICP. We reexamined ages of onset of ICP in a large, North American cohort of patients, and investigated the effects of genetic factors and alcohol use in patients with EO-ICP, LO-ICP, and ACP. Methods We performed a cross-sectional analysis of patients with CP of European ancestry enrolled in the North American Pancreatitis Study 2, a prospective study of 1195 patients with CP from 26 centers in the United States from August 2000 through December 2014. We compared age at onset of symptoms for 130 patients with CP who were lifetime abstainers from alcohol (61 patients with early onset and 69 patients with late onset), 308 light to moderate alcohol drinkers with CP, and 225 patients with ACP and heavy to very heavy alcohol use. DNA from available patients was analyzed for variants associated with CP in SPINK1, CFTR, and CTRC. The Kruskal–Wallis test was used to compare continuous variables across groups and based on genetic variants. Results Median ages at onset of symptoms were 20 years for patients with EO-ICP and no alcohol use, 58 years for patients with LO-ICP and no alcohol use, 47 years for light to moderate alcohol drinkers with CP, and 44 years for patients with ACP. A higher proportion of patients with EO-ICP had constant pain (65%) than patients with LO-ICP (31%) (P = .04). A higher proportion of patients with ACP had pseudocysts (43%) than patients with EO-ICP (11%) (P = .001). A higher proportion of patients with EO-ICP had pathogenic variants in SPINK1, CFTR, or CTRC (49%) than patients with LO-ICP (23%), light to moderate alcohol drinking with CP (26%), or ACP (23%) (P = .001). Among patients with variants in SPINK1, those with EO-ICP had onset of symptoms at a median age of 12 years, and light to moderate alcohol drinkers with CP had an age at onset of 24 years. Among patients with variants in CFTR, light to moderate alcohol drinkers had an age at onset of symptoms of 41 years, but this variant did not affect age at onset of EO-ICP or ACP. Conclusions We confirmed previously reported ages at onset of symptoms for EO-ICP and LO-ICP in a North American cohort. We found differences in clinical features among patients with EO-ICP, LO-ICP, and ACP. Almost half of patients with EO-ICP have genetic variants associated with CP, compared with approximately one quarter of patients with LO-CP or ACP. Genetic variants affect ages at onset of symptoms in some groups.

BACKGROUND & AIMS: Idiopathic chronic pancreatitis (ICP) is the second most common subtype of CP. In 1994, researchers reported the bimodal age at onset of ICP symptoms: early-onset ICP (EO-ICP; median age, 19.2 years) and late-onset ICP (LO-ICP; median age, 56.2 years). Ages of onset and clinical features of ICP differed from those of alcohol-related CP (ACP). However, variants in PRSS1 had not yet been associated with ICP. We reexamined ages of onset of ICP in a large, North American cohort of patients, and investigated the effects of genetic factors and alcohol use in patients with EO-ICP, LO-ICP, or ACP. METHODS: We performed a cross-sectional analysis of patients with CP of European ancestry enrolled in the North American Pancreatitis Study 2 studies, a prospective study of 1195 patients with CP from 26 centers in the United States from August 2000 through December 2014. We compared age at onset of symptoms for 130 patients with CP who were lifetime abstainers from alcohol (61 patients with early onset and 69 patients with late onset), 308 light to moderate alcohol drinkers with CP, and 225 patients with ACP and heavy to very heavy alcohol use. DNA from available patients was analyzed for variants associated with CP in SPINK1, CFTR, and CTRC. The Kruskal-Wallis test was used to compare continuous variables across groups and based on genetic variants. RESULTS: Median ages at onset of symptoms were 20 years for patients with EO-ICP and no alcohol use, 58 years for patients with LO-ICP and no alcohol use, 47 years for light to moderate alcohol drinkers with CP, and 44 years for patients with ACP. A higher proportion of patients with EO-ICP had constant pain (65%) than patients with LO-ICP (31%) (P=.04). A higher proportion of patients with ACP had pseudocysts (43%) than patients with EO-ICP (11%) (P=.001). A higher proportion of patients with EO-ICP had pathogenic variants in SPINK1, CFTR, or CTRC (49%) than patients with LO-ICP (23%), light to moderate alcohol drinking with CP (26%), or ACP (23%) (P=.001). Among patients with variants in SPINK1, those with EO-ICP had onset of symptoms at a median age of 12 years, and light to moderate alcohol drinkers with CP had an age at onset of 24 years. Among patients with variants in CFTR, light to moderate alcohol drinkers had an age at onset of symptoms of 41 years, but this variant did not affect age at onset of EO-ICP or ACP. CONCLUSIONS: We confirmed previously reported ages at onset of symptoms for EO-ICP and LOICP in a North American cohort. We found differences in clinical features among patients with EO-ICP, LO-ICP, and ACP. Almost half of patients with EO-ICP have genetic variants associated with CP, compared to about one-quarter of patients with LO-CP or ACP. Genetic variants affect ages at onset of symptoms in some groups.

Chronic pancreatitis (CP) is a complex disease associated with gene-gene or gene-environment interactions. The incidence of idiopathic CP has shown an increasing trend, withits phenotypeshaving changed considerably in the last two decades. The diseaseitself can be regulated before it reaches the stage of established CP; however, the etiopathogenesis underlying idiopathic CP remains to be established, making the condition difficult to cure. Unfortunately, there also remains a lack of consensus regarding the beneficial effects of antioxidant therapiesfor CP. It is known that antioxidant therapy does not reduce inflammatory and fibrotic cytokines, making it unlikely that they could modulate the disease process. Although antioxidants are safe, very few studies to date have reported the long-term beneficial effects in patients with CP. Thus, studies are being performed to identify drugs that can improve symptoms and alter the natural history of CP. Statins, with their numerous pleiotropic effects, may play a role in the treatment of CP, butin 2006, their use was found to be associated with the undesirable side effect of promoting pancreatitis. Latter studies showed favourable effects of statins in CP, highlighting the particular benefits of lipophilic statins, such as lovastatin and simvastatin, over the hydrophilic statins, such as rosuvastatin. Ultimately, studies to repurpose N-acetylcysteine as a CP therapy areyielding very promising results.

OBJECTIVE The study concerns identifying risk factors and developing nomogram for pancreatic pseudocyst (PPC) in idiopathic chronic pancreatitis (ICP) to facilitate early diagnosis. METHODS From January 2000 to December 2013, ICP patients admitted to our center were enrolled. Cumulative incidence of PPC was determined by Kaplan-Meier method. Patients were randomized into training group and validation group in a 2:1 ratio. Risk factors of PPC were determined through Cox proportional hazards regression model based on training cohort. The nomogram was constructed according to risk factors. RESULTS Totally, 1633 ICP patients were included with a median follow-up duration of 9.8 years. Pancreatic pseudocyst was observed in 14.7% (240/1633) of patients after ICP onset. The cumulative incidences of PPC were 8.2%, 10.4%, and 12.9% at 3, 5, and 10 years after ICP onset, respectively. Male sex, smoking history, history of severe acute pancreatitis, and chronic pain at/before diagnosis of ICP and complex pathologic changes in main pancreatic duct were recognized as risk factors of PPC development. The nomogram constructed with these risk factors achieved good concordance indexes. CONCLUSIONS Risk for PPC could be estimated through the nomogram. High-risk patients were suggested to be followed up closely to help early diagnosis of PPC.

Bimodal classification of idiopathic chronic pancreatitis (ICP) into early-onset (35 years) ICP was proposed in 1994 based on a study of 66 patients. However, bimodal distribution wasn’t sufficiently demonstrated. Our objective was to examine the validity and relevance of the age-based bimodal classification of ICP. We analyzed the distribution of age at onset of ICP in our cohort of 1633 patients admitted to our center from January 2000 to December 2013. Classify ICP patients into early-onset ICP(a) and late-onset ICP(a) according to different cut-off values (cut-off value, a = 15, 25, 35, 45, 55, 65 years old) for age at onset. Compare clinical characteristics of early-onset ICP(a) and late-onset ICP(a). We found slightly right skewed distribution of age at onset for ICP in our cohort. There were differences between early-onset and late-onset ICP with respect to basic clinical characteristics and development of key clinical events regardless of the cut off age at onset i.e. 15, 25, 35, 45 or even higher. The validity of the bimodal classification of early-onset and late-onset ICP could not be established in our large patient cohort and therefore such a classification needs to be reconsidered.

Pancreatic cancer carries poor prognosis. Establishing the diagnosis early could help in improving outcome. We are presenting a case of pancreatic cancer with delayed diagnosis. Our 60-year-old patient underwent multiple endoscopic ultrasound-guided biopsies with no evidence of malignancy. He had normal molecular tumor biomarkers. The patient needed 8 months to receive the diagnosis and initiate the treatment. There are no specific guidelines regarding choice of tissue sampling modalities in such cases.

Rare functionally defective carboxypeptidase A1 (CPA1) variants have been reported to predispose to nonalcoholic chronic pancreatitis, mainly the idiopathic subtype. However, independent replication has so far been lacking, particularly in Asian cohorts where initial studies employed small sample sizes. Herein we performed targeted next-generation sequencing of the CPA1 gene in 1112 Han Chinese idiopathic chronic pancreatitis (ICP) patients – the largest ICP cohort so far analyzed in a single population – and 1580 controls. Sanger sequencing was used to validate called variants, and the CPA1 activity and secretion of all newly found variants were measured. A total of 18 rare CPA1 variants were characterized, 11 of which have not been previously described. However, no significant association was noted with ICP irrespective of whether all rare variants [20/1112 (1.8%) in patients vs. 24/1580 (1.52%) in controls; P = 0.57] or functionally impaired variants [3/1112 (0.27%) in patients vs. 2/1580 (0.13%) in controls; P = 0.68] were considered. This article is protected by copyright. All rights reserved

Several recent studies have reported associations between gene mutations and chronic pancreatitis (CP); however, little is known about their association with risk of CP in the Chinese Han population. The aim of this study was to describe mutations in the cationic trypsinogen (PRSS1) and serine protease inhibitor Kazal type 1 (SPINK1) genes in patients with alcoholic chronic pancreatitis (ACP) and idiopathic chronic pancreatitis (ICP) and to investigate their influence on the clinical course of the disease. One hundred patients (24 with ACP, 76 with ICP) and 100 healthy volunteers (control group) were enrolled in the study. PRSS1 (R122H) mutations were detected in one (1.3%) patient with ICP and SPINK1 (N34S) mutations were present in one (4.1%) patient with ACP. PRSS1 and SPINK1 mutations were not detected in the control populations. There were no statistically significant differences between the CP patients and the control group. Those preliminary data suggest low prevalence of SPINK1 and PRSS1 mutations in the Chinese population, generally, as well as in CP patients, indicating that these mutations do not contribute to the development of CP.

Introduction: Chronic Pancreatitis (CP) is a progressive inflammatory disorder characterised by recurrent episodes of severe abdominal pain. Experimental studies demonstrated protective effects of statins in pancreatic fibrosis. Aim: To assess impact of simvastatin therapy on the severity of pain in patients with idiopathic CP or recurrent acute pancreatitis. Materials and Methods: This prospective, single centre and open-label study included patients with idiopathic CP and recurrent acute pancreatitis, depending upon inclusion and exclusion criteria. Patients were treated with either simvastatin (40 mg per day) (Group-A; n=25) or standard therapy (protonpump inhibitor and antioxidant therapy) (Group-B; n=25). Severity of the pain was assessed using a Visual Analogue Score (VAS) at the start of treatment and at 12-month of treatment. Results: Between June 2017 and August 2017, a total of 50 patients, age ranging from 18 years to 54 years, were included in the study. The study population predominantly included male patients (n=38). The intensity of pain in patients of Group-A reduced significantly (p=0.0001) from 8 (range 6-10) at baseline to 2 (range 0-9) after 12 months of the treatment. There was significant reduction in the intensity of pain in Group-B also {7 (range 6-10) at baseline vs. 5 (range 0-7); p=0.0001}. However, the reduction of VAS score was significantly higher in Group-A as compared to Group-B at 12-month follow-up {6 (range-1-8) vs. 3 (range 0-6); p=0.032}. Conclusion: Simvastatin treatment improved severity of pain in patients with CP or recurrent acute pancreatitis at 12-month follow-up. However, large randomised trials are needed to replicate these findings.

Background and aim Diabetes mellitus (DM) is a common complication of idiopathic chronic pancreatitis (ICP), which impairs the quality of life for patients. This study aimed to identify risk factors and develop nomogram for DM in ICP to help early diagnosis. Methods Idiopathic chronic pancreatitis patients admitted to our center from January 2000 to December 2013 were included. Cumulative rates of DM were calculated by Kaplan-Meier method. Patients were randomly assigned, in a 2:1 ratio, to the training and validation cohort. Based on training cohort, risk factors for DM were identified through Cox proportional hazards regression model, and nomogram was developed. Internal and external validations were performed based on the training and validation cohort, respectively. Results Totally, 1633 patients with ICP were finally enrolled. The median follow-up duration was 9.8 years. DM was found in 26.3% (430/1633) of patients after the onset of CP. Adult at onset of ICP, biliary stricture at/before diagnosis of CP, steatorrhea at/before diagnosis of CP, and complex pathologic changes in main pancreatic duct were identified risk factors for DM development. The nomogram achieved good concordance indexes in the training and validation cohorts, respectively, with well-fitted calibration curves. Conclusions Risk factors were identified, and nomogram was developed to determine the risk of DM in ICP patients. Patients with one or more of the risk factors including adult at onset of ICP, biliary stricture at/before diagnosis of CP, steatorrhea at/before diagnosis of CP, and complex pathologic changes in main pancreatic duct have higher incidence of DM.

Autoimmune Pancreatitis (AIP) presents in two forms - Type I or lymphoplasmacytic sclerosing pancreatitis and Type II or idiopathic ducto-centric pancreatitis (IDCP). AIP II is rare in south Asia and, especially so, in India. Most patients have either Idiopathic Chronic Pancreatitis (ICP) or alcohol related chronic pancreatitis. AIP Type I has been described in India. We herein report a patient who had features of ICP on imaging, for whom surgery was performed to relieve chronic pancreatic pain. However, the pathologic features revealed AIP Type II or IDCP.

Recent data suggest that the serine protease inhibitor Kazal type 1 (SPINK1) gene mutation is associated with idiopathic chronic pancreatitis. However, few studies have focused on the serine protease inhibitor Kazal type 1 c.194+2TC mutation. Therefore, our goal was to study the prevalence and impact of serine protease inhibitor Kazal type 1 mutations on the clinical profile of idiopathic chronic pancreatitis patients in China.A retrospective-cohort study of 118 Chinese patients with idiopathic chronic pancreatitis was performed, and genetic tests were carried out to detect SPINK1 mutations. Subjects without pancreatitis were used as controls. In total, 118 idiopathic chronic pancreatitis patients and 100 control subjects were evaluated.The serine protease inhibitor Kazal type 1 c.194+2TC variant was present in 44.9% of patients with idiopathic chronic pancreatitis. The frequency of diabetes in idiopathic chronic pancreatitis patients with the serine protease inhibitor Kazal type 1 c.194+2TC mutation (39.6%) was higher than that of patients without the mutation (9.2%). The time to occurrence of diabetes mellitus after idiopathic chronic pancreatitis symptom onset is significantly influenced by the c.194+2TC mutation (p0.001). In addition, the mean age of diabetes onset in patients with the serine protease inhibitor Kazal type 1 c.194+2TC mutation (38.33 ± 9.50) was significantly younger than that of patients without this mutation (49.67 ± 6.74).The presence of the serine protease inhibitor Kazal type 1 c.194+2TC mutation seems to be associated with idiopathic chronic pancreatitis and could predispose individuals to pancreatic diabetes onset at an earlier age.

CFTR mutations enhance susceptibility for idiopathic chronic pancreatitis (ICP) and congenital bilateral absence of the vas deferens (CBAVD); however, it is unknown why CFTR heterozygotes are at increased disease risk. We recently showed that common CFTR variants are associated with aberrantly spliced transcripts. Here, we genotyped for common CFTR variants and tested for associations in two ICP (ICP-A: 126 patients, 319 controls; ICP-B: 666 patients, 1,181 controls) and a CBAVD population (305 patients, 319 controls). Haplotype H10 (TG11-T7-470V) conferred protection (ICP-A: OR 0.19, P

A lateral pancreaticojejunostomy (LPJ), also known as the Puestow procedure, is a complex procedure performed for chronic pancreatitis when the pancreatic duct is dilated and unable to drain properly. Traditionally, these procedures are performed with open surgery. A minimally invasive approach to the LPJ using rigid handheld nonarticulating instruments is tedious and rarely performed. In fact, there are no prior laparoscopic case reports for LPJ in children and only a small handful of cases in the adult literature. This lack of laparoscopic information may be an indication of the difficulty in performing this complex operation with nonarticulating laparoscopic instruments. The advantages of robotic surgery may help overcome these difficulties. We present the first robotic LPJ ever reported in a 14-year-old child with idiopathic chronic pancreatitis. This case demonstrates the utility of this advanced surgical technology and may lead to a new minimally invasive option for both adults and children with chronic pancreatitis requiring surgical intervention.

Background The main cause of chronic pancreatitis (CP) is excessive alcohol consumption. On the other hand, only 5–10% of heavy drinkers develop chronic pancreatitis. We have only limited information regarding the pathogenic mechanism by which alcohol leads to the disease. Mutations of the PRSS1 and SPINK 1 have been mostly implicated in hereditary and idiopathic CP, but their presence in other types of this disease have also been reported. Aims The aim of the study was to determine the frequency of PRSS1 and SPINK1 mutations in patients with chronic alcoholic (ACP) and idiopathic pancreatitis (ICP) as well as to investigate their relation to the clinical course of the disease. Methods The study included 33 ACP and 14 ICP patients as well 46 healthy subjects. The diagnosis of CP was based on clinical data, ultrasound, and computed tomography. After isolation of DNA from peripheral blood two trypsinogen mutations were detected N29I and R122H by allelo-specific amplification polymerase chain reaction (ASA-PCR) and by the PCR-restriction fragment length polymorphism (RFLP). Beside this N34S mutation of SPINK1 was analyzed by PCR restriction fragment length polymorphism (PCR-RFLP). Results PRSS1 mutations have been detected in 11 (33%) patients with ACP. The frequency of the PRSS1 mutations was higher in patients with ACP than in controls (4.3%) (p

Portal hypertension has not been described as a complication of total pancreatectomy-islet auto-transplantation (TPIAT). We describe the first reported case of delayed and clinically significant portal hypertension following TPIAT in a patient with idiopathic chronic pancreatitis.

Background/Aims: Mutations in the PRSS1 and the SPINK1 genes have variably been associated with alcohol-related, idiopathic and hereditary chronic pancreatitis (CP). The aim of this study was to determine for the first time the significance of PRSS1, SPINK1 mutations and genetic variants of AAT in a group of Spanish patients with CP. Methods: 104 consecutive patients with CP were included, as well as 84 healthy control subjects. The R122H and N29I mutations in the PRSS1 gene, the N34S mutation in the SPINK1 gene and PiS and PiZ mutations in the AAT gene were analyzed by RFLP-PCR methods. Results: No R122H mutation was found in the PRSS1 gene, and N29I mutation was detected in 7.7% of CP patients. A N29I mutation was observed in 3.9% of patients with alcohol-related pancreatitis (ACP). A total of 5.8% of CP patients were identified with the N34S mutation. Genotype MS, SS and MZ were detected in 18.3, 3.8 and 1.3% of CP patients, respectively. Conclusion: The percentage of N29I mutations in ACP patients was higher than that reported in other studies, while the percentage of N34S and AAT mutations in ACP and idiopathic CP patients was similar. Copyright (C) 2009 S. Karger AG, Basel and IAP

金沢大学医薬保健研究域医学系, DNA analyses of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in japanese patients with idiopathic chronic pancreatitis (ICP) were performed to determine the relationship between the CFTR mutation and ICP. The study included patients with alcoholic pancreatitis (n = 20), patients with ICP (n = 20) and healthy volunteers (controls; n = 110). The poly-T region in intron 8 of the CFTR gene was analysed by direct sequencing. The CFTR coding region was screened using single-strand conformational polymorphism and direct sequencing. In the controls, frequencies of the 5T genotype and 5T allele were 4.5% and 3.6%, respectively. The frequency of the 5T genotype was significantly higher in the ICP group (20%) versus controls, but was not significantly different in alcolohol chronic pacreatitis patients (5%). Thus, the CFIR gene mutation, especially the 5T genotype, appears to have some relationship to ICP prevalence in japanese patients independent of cystic fibrosis. Copyright © 2009 Field House Publishing LLP.

Autoimmune pancreatitis is a rare but increasingly recognised entity, which may account for up to 7% of cases of idiopathic chronic pancreatitis. There are several characteristic imaging features associated with the disease however it often mimics pancreatic malignancy both clinically and radiologically, and may result in unnecessary surgery being performed. While autoimmune pancreatitis may involve the pancreas in isolation, almost half of these patients have manifestations of the disease in other organs. These additional sites of involvement may be identifiable radiologically and, when present, help confirm the diagnosis. We present a case of autoimmune pancreatitis with multiple extrapancreatic manifestations and review the available literature.

Chronic pancreatitis is usually caused by heavy alcohol intake and, in many studies, also smoking. Because heavy drinkers usually smoke, making it difficult to separate the effects of these 2 factors, we thought to study the impact of smoking on the progression of nonalcoholic idiopathic chronic pancreatitis (ICP) METHODS: We used data from 83 patients with ICP in Switzerland and from 83 patients in Italy. We studied the impact of smoking on progression of disease as measured by the appearance of calcification and diabetes using Cox regression models.In both centers, the prevalence of smoking was significantly higher in patients with ICP than in the background population. In Italian patients, smoking increased the risk of pancreatic calcifications (hazard ratio = 2.09; 95% confidence interval, 1.07-4.10). Smoking also shortened the time to appearance of calcification. Heavy smoking (20 cigarettes per day) was associated with the appearance of diabetes (hazard ratio = 3.94; 95% confidence interval, 1.14-13.6). For those patients who never reported consuming alcohol, smoking remains a significant risk factor.In nonalcoholic ICP, smoking is associated with disease progression as measured by the appearance of pancreatic calcification and, to a lower extent, of diabetes. These findings were chiefly observed in patients who were older than 35 years at the time of onset of disease.

BACKGROUND: Previous studies on gastrin levels in chronic pancreatitis (CP) patients have given conflicting results. These studies did not take into consideration the influence of Helicobacter pylori (H. pylori) infection on gastrin release. Also, there is no previous study that compared alcoholic CP patients to patients with idiopathic pancreatitis. Our aim was to measure basal and postprandial plasma gastrin levels in all CP patients, including subgroups of alcoholic, idiopathic, severe and mild CP patients, and compare them with healthy subjects after the eradication of H. pylori infection. PATIENTS AND METHODS: Basal and postprandial gastrin levels were measured in 30 patients with CP (10 patients with alcoholic and 20 patients with idiopathic CP) and in 25 healthy subjects. RESULTS: A significant increase in basal gastrin levels was found only in a subgroup of alcoholic CP (P

We present a case of 2 brothers with idiopathic chronic pancreatitis associated with pancreatic duct stones which could be successfully disintegrated by extracorporeal shock wave lithotripsy (ESWL). An obvious etiology for the pancreatolithiasis, like alcohol or biliary disease, was lacking and point mutations of the cationic trypsinogen gene exons 2 and 3 were not detected in the long arm of the 7th chromosome. However, a hereditary etiology could not be precluded since pancreatolithiasis occurred in the siblings. There has been no recurrence of pancreatic stones during 42 months of follow-up periods, for both. ESWL, the least invasive therapy, appeared applicable and effective for pancreatolithiasis in the present cases.

Idiopathic chronic pancreatitis accounts for up to one third of chronic pancreatitis cases. The most common inherited disease of the exocrine pancreas is cystic fibrosis, which is caused by mutations of a gene encoding an ion transport protein. It was discovered during the past year that many patients with idiopathic chronic pancreatitis have mutations of the gene that causes cystic fibrosis. This article reviews the evidence associating mutations of this gene with chronic pancreatitis and discusses the implications of this association for the evaluation, pathogenesis, classification, and possible prevention of pancreatitis.

Autoimmune Pancreatitis (AIP) is an emerging clinical entity found in 4.6-6 percent of patients with chronic pancreatitis [1]. It was first reported as an idiopathic chronic pancreatitis associated with hypergammaglobulinemia by Sarles et al. [2], with the term AIP being first used by Yoshida et al. [3]. In 2003, Notohara and coworkers described two types of AIP: Lymphoplasmacytic Sclerosing Pancreatitis (LPSP) termed “type 1 AIP” and idiopathic duct-centric chronic pancreatitis with Granulocyte Epithelial Lesion (GEL) termed “type 2 AIP” [1] (Table 1).

Over the past 5 years, several gain-of-function missense mutations in the human cationic trypsinogen gene (PRSS1, OMIM 276000) have been associated with hereditary and/or sporadic pancreatitis. This study reports a new pancreatitis-associated mutation—R116C (CGT > TGT: c.346C > T)—in the gene.

The evidence from recent surveys on chronic pancreatitis carried out around the world shows that alcohol remains the main factor associated with chronic pancreatitis, even if at a frequency lower than that reported previously. It has further confirmed that heavy alcohol consumption and smoking are independent risk factors for chronic pancreatitis. Autoimmune pancreatitis accounts for 2%-4% of all forms of chronic pancreatitis, but this frequency will probably increase over the next few years. The rise in idiopathic chronic pancreatitis, especially in India, represents a black hole in recently published surveys. Despite the progress made so far regarding the possibility of establishing the hereditary forms of chronic pancreatitis and the recognition of autoimmune pancreatitis, it is possible that we are more inaccurate today than in the past in identifying the factors associated with chronic pancreatitis in our patients.

The most common form of chronic pancreatitis (CP) in the Western world is alcoholic chronic pancreatitis (ACP), which represents 70–90% of patients with CP. Nearly all of the remaining patients (10–30%) are usually designated as having idiopathic chronic pancreatitis (ICP; 1, 2, 3, 4).

(2004). Clinical characterization of patients with idiopathic chronic pancreatitis and SPINK1 Mutations. Scandinavian Journal of Gastroenterology: Vol. 39, No. 9, pp. 903-904.

Background The role of mutations in the serine protease inhibitor Kazal type 1 (SPINK1) gene in chronic pancreatitis is still a matter of debate. Active SPINK1 is thought to antagonize activated trypsin. Cases of SPINK1 mutations, especially N34S, have been reported in a subset of patients with idiopathic chronic pancreatitis. However, the inheritance pattern is still unknown. Some cases with N34S heterozygosity have been reported with and without evidence for CP indicating neither an autosomal recessive nor dominant trait. Therefore SPINK1 mutations have been postulated to act as a disease modifier requiring additional mutations in a more complex genetic model. Familial hypocalciuric hypercalcemia (FHH) caused by heterozygous inactivating mutations in the calcium sensing receptor (CASR) gene is considered a benign disorder with elevated plasma calcium levels. Although hypercalcemia represents a risk factor for pancreatitis, increased rates of pancreatitis in patients with FHH have not been reported thus far. Methods We studied a family with a FHH-related hypercalcemia and chronic pancreatitis. DNA samples were analysed for mutations within the cationic trypsinogen (N29I, R122H) and SPINK1 (N34S) gene using melting curve analysis. Mutations within CASR gene were identified by DNA sequencing. Results A N34S SPINK1 mutation was found in all screened family members. However, only two family members developed chronic pancreatitis. These patients also had FHH caused by a novel, sporadic mutation in the CASR gene (518T>C) leading to an amino acid exchange (leucine->proline) in the extracellular domain of the CASR protein. Conclusion Mutations in the calcium sensing receptor gene might represent a novel as yet unidentified predisposing factor which may lead to an increased susceptibility for chronic pancreatitis. Moreover, this family analysis supports the hypothesis that SPINK1 mutations act as disease modifier and suggests an even more complex genetic model in SPINK1 related chronic pancreatitis.