Early-onset Idiopathic Chronic Pancreatitis Research Articles

Pregnancy Outcomes in Patients with Early-Onset Idiopathic Chronic Pancreatitis.

Early-onset idiopathic chronic pancreatitis (EOICP) is a disease that affects young individuals. Data on pregnancy outcomes in EOICP are limited. To assess the pregnancy outcomes in patients with EOICP andthe effect of pregnancy on the course of EOICP. Patients with EOICP with disease onset before their pregnancy were recruited. Data regarding demographic variables, disease duration, pregnancy outcomes, and course of illness were noted. 50 patients were included in the study contributing to a total of 86 pregnancies. The mean age of onset of symptoms and at the time of delivery was 17.95 (5.71) and 23.44 (4.28) years, respectively. Gestational diabetes (GD) and gestational hypertension (GH) noted in one (1.5%) each. 3 (4.5%) pregnancies were preterm. 19 (22.1%) pregnancies did not have successful outcomes (7 (8.1%) were induced abortions). 12 (15.2%) pregnancies had spontaneous pregnancy losses. 8 (10.1%) were spontaneous abortions and 4 (5.1%) were stillbirths. Of 67 successful pregnancies, 33 (49.3%) pregnancies were delivered by LSCS. Compared to average rates of LSCS in India, this was significantly higher (21.5% vs 49.3%-p ≤ 0.001). The average birth weight was 2.87 (0.48)kg. There was one (1.5%) neonatal death. Compared to the published Indian data, there was no significant difference in the incidence of spontaneous pregnancy losses, GD, GH, preterm labor, and birth weight. Pancreatic pain was reported by 21 (42%) women in total 27 (31.4%) pregnancies. There was no difference in maternal or fetal outcomes between pregnancies with or without pancreatic pain. There were no pancreatitis-related complications reported during the pregnancies. The present study shows that mothers affected with EOICP have pregnancy outcomes similar to healthy women in India.

A case of early-onset idiopathic chronic pancreatitis associated with a loss-of-function TRPV6 p.R483Q variant successfully treated by pancreatic duct stenting.

Several pancreatitis-related genetic variants have been identified. Recently, the association of loss-of-function variants in the transient receptor potential cation channel subfamily V member 6 (TRPV6) gene and early-onset non-alcoholic chronic pancreatitis (CP) has been reported. However, detailed clinical presentation of the cases carrying TRPV6 variants remains largely unknown. We report a case of early CP carrying a TRPV6 variant in which recurrent attacks of pancreatitis were successfully managed by pancreatic duct stenting. A 12-year-old boy with CP was referred to our hospital for further investigation. He had experienced recurrent pancreatitis attacks since he was 11years old. Pancreatic ductal anomalies were not identified on magnetic resonance cholangiopancreatography. Genetic analysis revealed that the patient had a loss-of-function TRPV6 c.1448G > A (p.R483Q) variant in a heterozygous form. Conservative treatments were not effective; thus, we placed pancreatic duct stent by endoscopic intervention, and the frequency of relapses have dramatically decreased. We present the first pediatric report of early CP associated with the TRPV6 variant that was successfully treated with pancreatic duct stenting. This case suggests that pancreatic duct stenting is effective in preventing the relapse of pancreatitis related to the TRPV6 variant.

Identification of novel factors that affect the onset of idiopathic chronic pancreatitis: The role for microRNA-323b-5p.

The c.194+2 T>C variant of serine protease inhibitor Kazal type 1 (SPINK1) is a known genetic risk factor found in Chinese patients with idiopathic chronic pancreatitis (ICP), but the early-onset mechanisms of ICP are still unclear. Complementary experimental approaches were used to pursue other potential pathologies in the present study. The serum level of SPINK1 of ICP patients in the Han population in China was detected and verified by an enzyme-linked immunosorbent assay. Next, differentially expressed proteins and microRNAs from plasma samples of early-onset and late-onset ICP patients were screened by proteomic analysis and microarray, respectively. Combined with these advanced methods, the data strongly suggest that the regulatory effects of microRNAs were involved in the early-onset mechanism of the ICP by in vitro experiments. There was no significant difference in the plasma SPINK1 expression between the early-onset ICP and the late-onset patients. However, the expression of plasma glutathione peroxidase (GPx3) in early-onset ICP patients was markedly lower than that in late-onset ICP patients, although the level of hsa-miR-323b-5p was lower in late-onset patients compared to the early-onset ICP group. In vitro experiments confirmed that hsa-miR-323b-5p could increase apoptosis in caerulein-treated pancreatic acinar cells and inhibit the expression of GPx3. The up-regulated hsa-miR-323b-5p might play a crucial role in the early-onset mechanisms of ICP by diminishing the antioxidant activity through the down-regulation of GPx3.

Chronic Pancreatitis in Thai Patients: A Comprehensive Review of 236 Patients from One Institution

Background: Reports of chronic pancreatitis (CP) in Thailand are rare. Clinical information is lacking. Objective: To study the etiology, genetics, presentations, clinical courses, complications, treatments, and outcomes of CP in Siriraj Hospital. Materials and Methods: Retrospective study of all CP patients during 2005 to 2018 was done. CP was diagnosed by abdominal radiography, ultrasonography, computed tomography (CT), endoscopic retrograde cholangiopancreatography (ERCP) or endoscopic ultrasonography (EUS). Etiology, genetics, presentations, clinical courses, complications, treatments and outcomes were analyzed. Results: There were 236 CP patients. The median follow-up was 37 months. There were 160 patients (68%) with alcoholic CP (ACP), 35 (15%) with early-onset idiopathic CP (E-ICP), 36 (15%) with late-onset idiopathic CP (L-ICP), 1 (0.4%) with tropical CP, 3 (1%) with hereditary pancreatitis (HP) and 1 (0.4%) with obstructive CP. Mean ages of onset were 47, 28 and 60 years in ACP, E-ICP and L-ICP, respectively (p<0.001). Male was predominant in all types of CP (98%, 40% and 56%; p<0.001). Initial presentations were abdominal pain (59%), recurrent acute pancreatitis (RAP, 22%), diabetes (DM, 8%) and steatorrhea (8%). Clinical manifestations during the course were abdominal pain in 89%, 89% and 83% (p = 0.832), RAP in 41%, 48% and 11% (p = 0.001), steatorrhea in 31%, 25% and 25% (p = 0.661), weight loss in 38%, 31% and 44% (p = 0.526), DM in 29%, 37% and 25% (p = 0.502), respectively. Median time to pain relief were 33, 74, and 16 months (p = 0.002). Common complications were pseudocyst (16%) and biliary obstruction (15%). SPINK1 mutation was detected in 83% of E-ICP, 45% of L-ICP and 21% of ACP (p<0.001). PRSS1 mutation was found in all HP. Medical therapy included analgesics (62%), pancreatic enzymes (76%) and antioxidants (9%). Endoscopic therapy was done in 48 patients (20%). Surgery was performed in 31 patients (13%). Conclusion: ACP, E-ICP and L-ICP are common etiologies of CP. Presentations were RAP, abdominal pain, DM and steatorrhea. Painless L-ICP was uncommon. Spontaneous pain relief occurred quickly. SPINK1 mutation was common in ICP. Endoscopic and surgical therapy were required in one-fifth. Keywords: Chronic pancreatitis, Etiology, Genetics, Management, Manifestation, Natural course, Review  

Classification of Early-Onset and Late-Onset Idiopathic Chronic Pancreatitis Needs Reconsideration

Bimodal classification of idiopathic chronic pancreatitis (ICP) into early-onset (<35 years) and late-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.

Differences in Age at Onset of Symptoms, and Effects of Genetic Variants, in Patients With Early vs Late-Onset Idiopathic Chronic Pancreatitis in a North American Cohort

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. 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. 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. 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.

Early-Onset and Late-Onset Idiopathic Chronic Pancreatitis in the North American Pancreatitis Study (NAPS2-CV) Cohort

Introduction: Idiopathic chronic pancreatitis (ICP) defines a group of patients in whom no etiology is evident after standard clinical work-up. ICP is heterogeneous and can be divided into early-onset ICP (EO-ICP) and late-onset ICP (LO-ICP). Layer et al reported clinical differences between EO-ICP and LO-ICP, inlcluding pain, pancreatic insufficiency, and clinical course at Mayo Clinic.[1] These findings have not been replicated or validated in an independent North American cohort. Aims: To compare features of ICP between the NAPS2-CV and Mayo Clinic cohorts and potentially validate classification of ICP into EO-ICP and LO-ICP groups. Methods: NAPS2-CV prospectively ascertained patients with chronic pancreatitis using detailed demographic, phenotypic, and etiological case report forms. The diagnosis of ICP was made by expert physicians and then divided by age (EO-ICP: <35 years, and LO-ICP >35 years). We compared the clinical features of the NAPS2-CV and Mayo Clinic cohorts. Results: ICP was identified in 126/521 (24%). The fractions of ICP as EO-ICP versus LO-ICP were similar between NAPS2-CV and Mayo cohorts. Patients with EO-ICP were more likely to have pain than LO-ICP. EO-ICP and LO-ICP had similar rates of exocrine insufficiency, endocrine insufficiency, and calcifications. Prevalence of distinct clinical features were similar between NAPS2-CV and Mayo cohorts (Table). Conclusion: EO-ICP and LO-ICP differ primarily with respect to pain. The clinical profiles of NAPS2-CV replicate Layer. Further insights will require analysis of deeper data sets.Table 1

Clinical profile of early-onset and late-onset idiopathic chronic pancreatitis in South India

Idiopathic chronic pancreatitis (ICP) is the most common form of chronic pancreatitis reported in India. There is paucity of literature on the prevalence and profiles of early- and late-onset forms of ICP in India. We compared the profile of early- and late-onset ICP in a patient population attending a tertiary care hospital in South India. Pain was the characteristic feature as more than 90 % with both early-onset and late-onset ICP had pain as the most significant symptom. Onset of pain was at age 14.9 ± 7.7 years in early-onset and at 38.1 ± 9.9 in late-onset ICP (p < 0.001). There was considerable delay between onset of pain in early onset as compared to late-onset ICP. Diabetes was seen in 41.4 % in early-onset as compared to 69.1 % in late-onset ICP (p < 0.001). Pancreatic exocrine insufficiency was seen in 34.4 % in early-onset as compared to 53.2 % in late-onset ICP (p < 0.001). Increased prevalence of exocrine insufficiency and diabetes was observed in late-onset as compared to early-onset ICP. Univariate analysis showed that alcohol use, smoking, age, and family history of diabetes were significantly associated with diabetes. Multivariate analysis showed strong associations for diabetes with smoking (odds ratio (OR) = 4.2), calcification (OR = 7.7), as well as family history and age >40 years. There were differences between early-onset and late-onset ICP in southern Indian patients. Diabetes was strongly associated with smoking and pancreatic calcification.

Clinical Profile of Idiopathic Chronic Pancreatitis in North India

Tropical pancreatitis, a form of idiopathic chronic pancreatitis (ICP) with unique features, has been described in South and North India. We investigated the clinical profile of ICP patients in North India. Detailed demographic data were recorded; hematological and biochemical analyses were performed on samples from 155 patients (mostly from North India) who had been diagnosed with chronic pancreatitis. Ultrasonography and computed tomography were performed on all patients. Magnetic resonance cholangiopancreatography, endoscopic retrograde cholangiopancreatography, glucose tolerance tests, and fecal fat studies were performed on some patients. Patients were divided into groups based on early- or late-onset ICP (before or after 35 years of age). ICP was reported in 41.3% of patients and alcoholic chronic pancreatitis in 38.1%. The mean age of ICP patients was 33.0 +/- 13.0 years and the mean duration of symptoms at the time of presentation was 40.2 +/- 34.4 months. Pain was the dominant symptom in patients with early- (95.1%) and late-onset (100%) ICP; pseudocyst was the most common local complication. Diabetes was observed in 17.1% of patients with early-onset ICP and 34.8% with late-onset ICP. Pancreatic calcification was noted in 46.3% of patients with early-onset and 47.8% with late-onset ICP. Pseudocyst and segmental portal hypertension occurred more frequently in non-calcific ICP, whereas diabetes mellitus and abnormal fecal fat excretion occurred more frequently in patients with calcific ICP. In North India, ICP differs from the classical tropical pancreatitis described in the literature. It is associated with a higher prevalence of pain and lower frequencies of diabetes, calcification, and intraductal calculi.

Idiopathic chronic pancreatitis in children: MR cholangiopancreatography after secretin administration.

To assess the accuracy of dynamic magnetic resonance (MR) cholangiopancreatography after secretin administration in detecting pancreatic duct abnormalities typical of early-onset idiopathic chronic pancreatitis in children with recurrent episodes of idiopathic acute pancreatitis. Fifteen children (mean age, 11.3 years; range, 6-17 years) with at least three recurrent episodes of idiopathic acute pancreatitis prospectively underwent MR cholangiopancreatography before and after secretin administration. Image analysis included visualization of side branches, ductal narrowing, endoluminal filling defects, irregular ductal contour, cavities, and pancreas divisum. All patients underwent endoscopic retrograde cholangiopancreatography (ERCP). Dilated side branches were detected in three (20%) of 15 patients on MR cholangiopancreatograms obtained before secretin administration and in seven (47%) of 15 patients on images obtained after secretin administration. Ductal narrowing was detected in one (7%) of 15 patients on images obtained before secretin administration and in two (13%) of 15 patients on images obtained after secretin administration. Endoluminal filling defects in one (7%) of 15 patients were observed on MR cholangiopancreatograms obtained both before and after secretin administration. Irregular contour of the main pancreatic duct was present in four (27%) of 15 patients on MR cholangiopancreatograms obtained before secretin administration and in five (33%) of 15 patients on images obtained after secretin administration. Cavities and pancreas divisum were detected in one (7%) of 15 patients and in two (13%) of 15 patients, respectively, only on MR cholangiopancreatograms obtained after secretin administration. Secretin improves the sensitivity of MR cholangiopancreatography in diagnosing early-onset idiopathic chronic pancreatitis.

Mutations of the serine protease inhibitor, Kazal type 1 gene, in patients with idiopathic chronic pancreatitis

OBJECTIVE: The pathogenesis of chronic pancreatitis (CP) is poorly understood. Genetic studies revealed mutations in the cationic trypsinogen gene and an increased frequency of cystic fibrosis gene mutations in patients with CP. Recently, a point mutation (N34S) in the gene encoding the serine protease inhibitor, Kazal type 1 (SPINK1), was found in approximately 20% of patients with CP. The aim of our study was to determine the frequency of the N34S SPINK1 gene mutation in a well-defined patient cohort with idiopathic CP (ICP) and to compare the incidence with healthy controls. In addition, we investigated the impact of this mutation on the long-term course of CP. METHODS: Fourteen patients with early-onset and four patients with late-onset CP of our well-defined pancreatitis cohort were enrolled in the present study, and 397 healthy individuals served as a control population. Coding exonic and the flanking intronic sequences of SPINK1 were investigated by direct DNA sequencing. The mutations found were confirmed by melting curve analysis. In addition, the N34S mutation was detected by analyzing the DNA fragments generated by digestion with restriction enzyme TspR I. Clinical data of patients with the N34S mutation were compared with those without mutations. RESULTS: The N34S mutation was detected in six of 14 (43%) patients with early-onset ICP. One patient was homozygous, and five patients were heterozygous for this mutation. The N34S mutation in a heterozygous state was found in four of 397 healthy controls (1.0%). The different allele frequency observed (seven of 28 vs four of 794) was significant (odds ratio = 66, 95% CI = 18–242, p < 0.0001). The clinical course was similar in patients with a mutation compared with those without a mutation. No other SPINK1 mutations were detected. The N34S mutation was not found in patients with late-onset ICP. CONCLUSIONS: Our results indicate that the N34S mutation in the SPINK1 gene is strongly associated with ICP, especially with the early-onset type. The natural course is similar in patients with mutations compared with SPINK1 mutation-negative patients. The N34S mutation may easily be screened for by restriction digestion with TspR I.

Mutations of the serine protease inhibitor, Kazal type 1 gene, in patients with idiopathic chronic pancreatitis.

The pathogenesis of chronic pancreatitis (CP) is poorly understood. Genetic studies revealed mutations in the cationic trypsinogen gene and an increased frequency of cystic fibrosis gene mutations in patients with CP. Recently, a point mutation (N34S) in the gene encoding the serine protease inhibitor, Kazal type 1 (SPINK1), was found in approximately 20% of patients with CP. The aim of our study was to determine the frequency of the N34S SPINKI gene mutation in a well-defined patient cohort with idiopathic CP (ICP) and to compare the incidence with healthy controls. In addition, we investigated the impact of this mutation on the long-term course of CP. Fourteen patients with early-onset and four patients with late-onset CP of our well-defined pancreatitis cohort were enrolled in the present study, and 397 healthy individuals served as a control population. Coding exonic and the flanking intronic sequences of SPINK1 were investigated by direct DNA sequencing. The mutations found were confirmed by melting curve analysis. In addition, the N34S mutation was detected by analyzing the DNA fragments generated by digestion with restriction enzyme TspR I. Clinical data of patients with the N34S mutation were compared with those without mutations. The N34S mutation was detected in six of 14 (43%) patients with early-onset ICP. One patient was homozygous, and five patients were heterozygous for this mutation. The N34S mutation in a heterozygous state was found in four of 397 healthy controls (1.0%). The different allele frequency observed (seven of 28 vs four of 794) was significant (odds ratio = 66, 95% CI = 18-242, p < 0.0001). The clinical course was similar in patients with a mutation compared with those without a mutation. No other SPINKI mutations were detected. The N34S mutation was not found in patients with late-onset ICP. Our results indicate that the N34S mutation in the SPINKI gene is strongly associated with ICP, especially with the early-onset type. The natural course is similar in patients with mutations compared with SPINK1 mutation-negative patients. The N34S mutation may easily be screened for by restriction digestion with TspR I.

Endotherapy of early onset idiopathic chronic pancreatitis: Results with long-term follow-up

Background: Idiopathic chronic pancreatitis that presents at age 35 years or younger has been classified as early onset type and is often characterized by chronic severe pain. Endotherapy, with drainage of the main pancreatic duct, can lead to control of pain if ductal hypertension is an important cause. Long-term results of endotherapy in patients with early onset idiopathic chronic pancreatitis are reported herein. Methods: This retrospective study consists of 11 patients (6 men, 5 women; mean age 24.2 years, range 16-34 years) treated endoscopically in a 6.5-year period. The indication for treatment was pain in all patients and all had a dilated main pancreatic duct on pancreatography. The objectives of endoscopic treatment were to obtain good drainage of the pancreatic duct and complete clearance of ductal stones. Results: Treatment was successful in all patients with no procedure-related mortality and with mild complications. Seven patients remained free of pain relapses after a mean follow-up of 78.3 months (37-116 months). Seven relapses of pain were recorded in the remaining 4 patients. Endoscopic retreatment was successful in all cases. The difference between the number of hospitalizations during the year before treatment (mean 2.2, range 1-9) and the year after (mean 0.3, range 0-2) was statistically significant (p < 0.01). Statistical significance was maintained at 3 and 6 years' follow-up. Conclusions: Endoscopic treatment could be regarded as the initial management of choice for patients with early onset idiopathic chronic pancreatitis. (Gastrointest Endosc 2002;55:488-93.)

The Effect of Small Amounts of Alcohol on the Clinical Course of Chronic Pancreatitis

To investigate the hypothesis that an increasing intake of alcohol accelerates the course of chronic pancreatitis. In this retrospective record analysis and subsequent prospective follow-up of 372 patients with chronic pancreatitis, we separately compared the clinical course of chronic pancreatitis among the following patients: those with early-onset idiopathic chronic pancreatitis and no alcohol intake (group A [n=25]) and those with late-onset idiopathic chronic pancreatitis and no alcohol intake (group B [n=41]), low alcohol intake (< 50 g/d) (group C [n=57]), and high alcohol intake (> or = 50 g/d) (group D [n=249]). From medical records, physical examinations, questionnaires, death certificates, or autopsy reports, we obtained information on sex, age, signs and symptoms (pain severity, calcification, endocrine and exocrine insufficiency), complications, surgery, and survival. Group D had the highest percentage of men (72%). At the onset of chronic pancreatitis, patients in group A were significantly younger than those in groups B, C, and D (P<.05), and severity of pain was significantly greater in patients in group A than in groups B, C, and D (P<.05). The percentage of patients who eventually developed endocrine or exocrine insufficiency was similar in all groups. Among patients in groups B, C, and D, an increasing intake of alcohol from zero to less than 50 g/d to more than 50 g/d was associated with earlier inception of disease (P<.001). Pain prevalence at onset was less in group B patients than in patients in groups C and D (P<.05). Intake of a large amount of alcohol (group D) shortened time to calcification and survival (P<.05). In addition, patients in group D had more complications (fistulas, pseudocysts, abscesses, and biliary obstruction) (P<.05) than those in groups A and B. More patients in group A underwent pancreatic surgery compared with patients in groups B and C. Among patients with onset of chronic pancreatitis after age 35 years, alcohol intake, even less than 50 g/d, induced earlier disease characterized by more frequent severe pain, calcification, and complications. Intake of large amounts of alcohol (> or = 50 g/d) reduced time to calcification and death.

Cigarette smoking increases the risk of pancreatic calcification in late-onset but not early-onset idiopathic chronic pancreatitis.

An association exists between cigarette smoking and pancreatitis owing to alcohol. We determined whether cigarette smoking affected the course of pancreatic calcification and insufficiency in idiopathic chronic pancreatitis. Medical records were analyzed of 24 persons with early- and 42 with late-onset idiopathic chronic pancreatitis who were diagnosed between 1976 and 1982 and then followed prospectively until 1985. Smoking equaled >5 pack-years before calcification or insufficiency or last follow-up. Mean follow-up after onset of chronic pancreatitis was 27 and 13 years in early- and late-onset idiopathic chronic pancreatitis, respectively. Incidence of calcification in the two groups was 58 and 43%, respectively. In early-onset idiopathic chronic pancreatitis, smokers and nonsmokers developed calcification at a similar rate and frequency (58%). In late-onset idiopathic chronic pancreatitis, smokers developed pancreatic calcifications faster (p < 0.001) and more frequently (83 vs. 13%, p < 0.001) than nonsmokers. The association between smoking and pancreatic calcification was independent of gender, body mass index, and exocrine or endocrine insufficiency. Smoking did not affect development of exocrine or endocrine insufficiency. Cigarette smoking increases the risk of pancreatic calcification of late- but not of early-onset idiopathic chronic pancreatitis. These data support encouraging cessation of smoking in chronic pancreatitis.