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Background: Early-onset idiopathic chronic pancreatitis (EOICP) is a disease that affects young individuals. Data on pregnancy outcomes in EOICP are limited. Aim: To assess the pregnancy outcomes in patients with EOICP and the effect of pregnancy on the course of EOICP. Methods: 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. Results: 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. Conclusion: The present study shows that mothers affected with EOICP have pregnancy outcomes similar to healthy women in India. [ABSTRACT FROM AUTHOR]

Background and Aims: Chronic pancreatitis (CP) is a fibroinflammatory syndrome of the pancreas associated with pain and poor quality of life. It has toxic and genetic risk factors but can also be idiopathic. The natural history of idiopathic CP (ICP) is not well-known. Therefore, we studied clinical characteristics and outcomes of these patients followed in our Pancreas Center. Methods: Review of CP patients between January 1, 2016, and April 30, 2021. Patients were divided into 2 groups based on diagnosis, ICP vs non-ICP. CP patients with a smoking history were placed in the non-ICP group. Statistical analysis was performed to identify differences in demographics, comorbidities, complications, controlled medications, and resource utilization. Results: Out of 450 patients, 101 (22%) were diagnosed with ICP and 349 (78%) were non-ICP. ICP patients were mainly female (59.4% vs 40.5%; P = .005), had less comorbid anxiety (10.5% vs 22.1%; P = .002), depression (24.2% vs 35.8%; P < .001), disability (13% vs 16.3%; P = .021), exocrine pancreatic insufficiency (45.3% vs 62.6%; P = .004), splanchnic vein thrombosis (1.04% vs 14.9%; P < .001), pseudocysts (16.7% vs 41.6%; P < .001), and biliary obstruction (3.12% vs 19.2%; P < .001). They underwent less abdominal imaging (2.63 vs 3.42; P = .048) and endoscopic retrograde cholangiopancreatography (0.88 vs 1.32; P = .030). They also had less opioid use (29.6% vs 54.4%; P < .001), gabapentinoid use (34% vs 52.3%; P = .002), and celiac blocks (7.22% vs 16.1%; P < .041). Conclusion: Our study demonstrates that the clinical course of ICP is less morbid compared to non-ICP. This study specifically removes smoking, a significant risk factor for CP, to study a truly idiopathic cohort.

Background: Tobacco smoking is a known risk factor for progression of chronic pancreatitis (CP). Aim: We compare clinical outcomes of CP patients with current or former smoking with those who have never smoked. Methods: We reviewed all patients with followed at our Pancreas Center from 2016 to 2021, comparing the demographics, clinical features, comorbidities, outcomes, and resource utilization between smokers and non-smokers. Results: Of 439 CP patients, 283 were smokers (125 current, 158 former). Significantly more smokers were men (58.3% vs 40.4%), with alcoholic CP (45.5% vs 12.1%), chronic abdominal pain (77.7% vs 65.4%), anxiety and depression (22.6% vs 14.1% and 38.9% vs 23.1%), and with more local pancreatic complications [splanchnic vein thrombosis (15.7% vs 5.13%), pseudocyst (42.7% vs 23.7%), biliary obstruction (20.5% vs 5.88%)], exocrine pancreatic insufficiency (65.8% vs 46.2%), hospitalizations (2.59 vs 1.75 visits), and emergency department visits (8.96% vs 3.25%). Opioid and neuromodulator use were significantly higher (59.2% vs 30.3% and 58.4% vs 31.2%). Current smokers had worse outcomes than former smokers. Multivariate analysis controlling for multiple factors identified smoking as an independent predictor of chronic abdominal pain (OR 2.49, CI 1.23–5.04, p = 0.011), opioid (OR 2.36, CI 1.35–4.12, p = 0.002), neuromodulators (OR 2.55, CI 1.46–4.46, p = 0.001), and non-opioid-controlled medications (OR 2.28, CI 1.22–4.30, p = 0.01) use, as well as splanchnic vein thromboses (OR 2.65, CI 1.02–6.91, p = 0.045) and biliary obstruction (OR 4.12, CI 1.60–10.61, p = 0.003). Conclusion: CP patients who smoke or formerly smoked have greater morbidity and worse outcomes than non-smokers. [ABSTRACT FROM AUTHOR]

Aim: To study polymorphisms in glutathione-S-transferases (GST-T1, GST-M1, GST-P1) and uridine-5′-diphosphate-glucuronosyl-transferases (UGT1A7) genes and the risk of developing chronic pancreatitis (CP) associated with these polymorphisms. Methods: This study included 49 alcoholic and 51 idiopathic chronic pancreatitis patients, 50 alcohol addicts and 50 healthy controls. Polymorphism(s) in GST-T1 and GST-M1 genes were assessed by multiplex polymerase chain reaction (PCR), while PCR–radiofrequency lesioning (RFLP) was employed to assess the same in GST-P1 and UGT1A7 genes. The differences in polymorphism frequency between groups and the risk of developing pancreatitis were assessed by the odds ratio. Results: Strong association of the null genotype of GST-T1 with CP susceptibility was observed. Alcoholics with the Val allele of GST-P1 have higher chances of having pancreatitis. Idiopathic pancreatitis patients with higher age at the onset of pain were found to have the null genotype of GST-M1. Conclusion: Alcoholics with the null genotype of the GST-T1 gene and the Valine allele of the GST-P1 gene are at a higher risk of developing CP. Thus, genotyping of these genes may serve as an important screening tool for the identification of high-risk groups among alcoholics. [ABSTRACT FROM AUTHOR]

Background/Aims The prevalence and natural history of SPINK1, PRSS1, and CFTR mutations in idiopathic pancreatitis (ICP) are not well-documented. This study evaluates the prevalence, genetic and clinical characteristics, and long-term outcomes of gene-associated chronic pancreatitis (GCP) compared to alcoholic chronic pancreatitis (ACP). Methods From January 1997 to July 2023, a cohort of 711 ICP patients underwent DNA testing for SPINK1, PRSS1, and CFTR mutations. A propensity score-matched analysis was conducted to compare GCP to ACP patients at a 1:3 ratio. Results Gene mutations were identified in 23.2% of idiopathic pancreatitis patients, with SPINK1 being the most common mutation (70%). GCP patients experienced significantly more pancreatic pain (89.3% vs. 70.7%) and had a shorter median time to symptom onset (26.2 years vs. 42.6 years) compared to ACP patients. Pancreatic cancer was observed in 3.6% of GCP patients, with a cumulative risk reaching 16.7% by age 70, while the incidence was lower in ACP patients. Although GCP patients exhibited higher cumulative risks, the hazard ratio for gene mutation status was not statistically significant (HR: 1.53). However, a Cambridge classification grade ＞3 was a significant predictor of pancreatic cancer outcomes (HR: 4.58, p=0.034). Conclusion GCP patients exhibit distinct clinical characteristics and outcomes compared to ACP patients, necessitating individualized evaluation and management strategies. Given the significant cumulative risk of pancreatic cancer in GCP, early and regular surveillance is recommended, particularly for those with higher Cambridge classification grades. [ABSTRACT FROM AUTHOR]

Certain cases of chronic pancreatitis (CP) occur without an apparent causative factor, diagnosed as idiopathic CP (ICP). Several studies have reported that ICP was associated with mutations in the SPINK1 and PRSS1 genes, but the studies were not conclusive as these polymorphisms can also occur in healthy individuals. In the present study, we aimed to study the genotypes of SPINK1 and PRSS1. Our study recruited nine ICP patients having no known risk factors. Symptoms relating to ICP were recorded. Genetic studies were performed in all ICP patients and 230 healthy controls. SPINK1 mutations in cases and controls were genotyped by genotyping assay. The entire PRSS1 gene was sequenced in all cases and controls to look for any mutations. Statistical analysis of genotypes and minor allele frequencies (MAF) was performed. All of the 9 ICP patients had SPINK1 mutations. The SPINK1 N34S heterozygous mutation (MAF 2.17%) was detected in 10 out of 230 controls, while the IVS3+2T>C mutation was not detected in any. PRSS1 mutations were detected in no cases or controls. In summary, SPINK1 mutations were associated with ICP. SPINK1 N34S carrier status was found in the general population with low prevalence, while IVS3+2T>C was rarely found in the controls.

Objectives: Steatorrhea, a sign of severe pancreatic exocrine insufficiency (PEI), is related to consequences caused by pancreatitis. This study aimed to identify predictors and to construct a nomogram for steatorrhea in idiopathic chronic pancreatitis (ICP). Methods: ICP patients admitted to our hospital from January 2000 to December 2013 were enrolled in this retrospective–prospective cohort study and randomly assigned to the training and validation cohorts. The cumulative rate of steatorrhea was calculated. A Cox proportional hazard regression model was used to identify predictors for steatorrhea and construct the nomogram. Internal and external validation of the nomogram was then performed. Results: There were 1633 ICP patients enrolled, with a median follow‐up duration of 9.8 years and 20.8% (339/1633) of patients developed steatorrhea following onset of ICP. Steatorrhea was observed in 93, 115, and 133 patients at 1, 3, and 5 years following diagnosis of CP, with a cumulative rate of 6.5% (95% confidence interval [CI] 5.1%–7.9%), 8.0% (95% CI 6.2%–9.8%), and 9.3% (95% CI 6.6%–12.0%), respectively. Male sex (hazard ratio [HR] 2.479, P < 0.001), diabetes mellitus at/before diagnosis of ICP (HR 2.274, P = 0.003), and aged less than 18 years at onset of ICP (HR 0.095, P < 0.001) were identified risk factors for steatorrhea. Initial manifestations were associated with development of steatorrhea. The nomogram was proven to have good concordance indexes. Conclusions: We identified predictors and developed a nomogram for predicting steatorrhea in ICP. It was recommended that high‐risk populations be followed up closely, which might contribute to the early diagnosis and treatment of PEI. [ABSTRACT FROM AUTHOR]

Tropical chronic pancreatitis (TCP) is a special variant of idiopathic chronic pancreatitis that is seen mainly in tropical countries. Although the prevalence of tropical pancreatitis is high in southern India, it is reported from most parts of India. It occurs usually in young people, involves the main pancreatic duct, and results in large ductal calculi with high incidence of diabetes and malignancy. Recent reports suggest that the presentation is changing. The age of onset is older and the disease course seems to be milder. The etiology is not known, but genetic mutations and environmental factors are likely causes. This article is a narrative review of the recent trends in the etiopathogenesis and management of tropical calcific pancreatitis (TCP). Extensive literature search was done from PubMed and Ovid. Article was prepared by reviewing full-text articles and abstracts related to chronic calcific pancreatitis (CCP) and TCP. [ABSTRACT FROM AUTHOR]

Certain cases of chronic pancreatitis (CP) occur without an apparent causative factor, diagnosed as idiopathic CP (ICP). Several studies have reported that ICP was associated with mutations in the SPINK1 and PRSS1 genes, but the studies were not conclusive as these polymorphisms can also occur in healthy individuals. In the present study, we aimed to study the genotypes of SPINK1 and PRSS1. Our study recruited nine ICP patients having no known risk factors. Symptoms relating to ICP were recorded. Genetic studies were performed in all ICP patients and 230 healthy controls. SPINK1 mutations in cases and controls were genotyped by genotyping assay. The entire PRSS1 gene was sequenced in all cases and controls to look for any mutations. Statistical analysis of genotypes and minor allele frequencies (MAF) was performed. All of the 9 ICP patients had SPINK1 mutations. The SPINK1 N34S heterozygous mutation (MAF 2.17%) was detected in 10 out of 230 controls, while the IVS3+2T>C mutation was not detected in any. PRSS1 mutations were detected in no cases or controls. In summary, SPINK1 mutations were associated with ICP. SPINK1 N34S carrier status was found in the general population with low prevalence, while IVS3+2T>C was rarely found in the controls. [ABSTRACT FROM AUTHOR]

Tropical chronic pancreatitis (TCP) is a special variant of idiopathic chronic pancreatitis that is seen mainly in tropical countries. Although the prevalence of tropical pancreatitis is high in southern India, it is reported from most parts of India. It occurs usually in young people, involves the main pancreatic duct, and results in large ductal calculi with high incidence of diabetes and malignancy. Recent reports suggest that the presentation is changing. The age of onset is older and the disease course seems to be milder. The etiology is not known, but genetic mutations and environmental factors are likely causes. This article is a narrative review of the recent trends in the etiopathogenesis and management of tropical calcific pancreatitis (TCP). Extensive literature search was done from PubMed and Ovid. Article was prepared by reviewing full-text articles and abstracts related to chronic calcific pancreatitis (CCP) and TCP. [ABSTRACT FROM AUTHOR]

The carboxyl-ester lipase (CEL) gene contains a variable number of tandem repeats (VNTR) region. It remains unclear whether the number of repeats in the CEL VNTR is related to the risk of pancreatic diseases. The aim of this study was to investigate whether CEL VNTR length is associated with idiopathic chronic pancreatitis (ICP), alcoholic chronic pancreatitis (ACP), or pancreatic cancer in a cohort of Chinese patients. CEL VNTRs were genotyped in patients diagnosed with ICP (n = 771), ACP (n = 222), or pancreatic cancer (n = 263), and in healthy controls (n = 927). CEL VNTR lengths were determined using a screening method combining PCR and DNA fragment analysis. Overall, the CEL VNTR lengths ranged from 5 to 22 repeats, with the 16-repeat allele ('normal' size, N) accounting for 73.82% of all observed alleles. The VNTR allele frequencies and genotype distributions were not significantly different between healthy controls and patients with ACP or pancreatic cancer. For the ICP group, allele frequencies did not differ significantly from the controls, while the frequency of the SS genotype (homozygosity for 5–15 repeats) was significantly higher in the patients (4.67%) than in the controls (1.94%) (p = 0.0014; OR = 2.47; 95% CI = 1.39–4.39). There were no associations between the CEL VNTR length and ACP or pancreatic cancer. However, homozygosity for short VNTR lengths may confer susceptibility to ICP. [ABSTRACT FROM AUTHOR]

/Objectives: A recent Genome-wide Association Study (GWAS) in alcoholic chronic pancreatitis (ACP) identified a novel association with the CTRB1-CTRB2 (chymotrypsinogen B1, B2) locus, linked to a 16.6 kb inversion that was confirmed in non-alcoholic chronic pancreatitis (NACP). Moreover, recent findings on the function of CTRB1 and CTRB2 suggest a protective role in pancreatitis development. The aim of the present study was to investigate the CTRB1-CTRB2 locus for rare genetic variants associated with chronic pancreatitis (CP). We analyzed 134 patients with ACP and 203 patients with NACP and compared them to up to 258 healthy controls. Genotyping was performed with polymerase chain reaction, followed by Sanger sequencing of all exons and the exon-intron-boundaries of CTRB1 and CTRB2. Finally, in silico analyses of the identified variants were conducted. None of the seven rare missense variants or the single 5′-UTR variant in CTRB1 and CTRB2 was associated with ACP or NACP. In silico analysis predicted that variant p. Trp5Leu in CTRB1 and variant c.-4C > T in CTRB2 might alter protein expression and variants p. Asp222His in CTRB1 and p. Ala247Thr in CTRB2 might affect protein function. However, all of these variants were also described in public databases. The present study did not reveal an association of rare variants in CTRB1 and CTRB2 with ACP or NACP. Although rare missense variants were almost exclusively found in patients, only four variants were predicted to affect protein expression or function. Thus, a major influence of rare variants in the CTRB1 - CTRB2 locus on CP development is unlikely. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background The cystic fibrosis transmembrane conductance regulator ( CFTR ) has been reported to influence individual susceptibility to chronic pancreatitis (CP), but the results of previous studies are controversial. Aims We performed a study to demonstrate the relationship between CFTR and CP. Methods We searched PubMed, Scopus, and Embase for studies of patients with CP. Seven studies from 1995 to 2016 were identified, and included 64,832 patients. Pooled prevalence and 95% confidence intervals (CIs) were calculated. Results F508 deletion in CFTR was significantly positively associated with CP risk in the overall analysis (odds ratio [OR] = 3.20, 95% CI: 2.30–4.44, I 2 = 31.7%). In subgroup analysis stratified by ethnicity, F508 deletion was significantly associated with CP risk in Indian populations, using a fixed effects model (ORs = 5.45, 95% CI: 2.52–11.79, I 2 = 0.0%), and in non-Indian populations, using a random effects model (ORs = 3.59, 95% CI: 1.73–7.48, I 2 = 60.9%). At the same time, we found that Indians with F508 deletion had much higher CP prevalence than non-Indians. Interestingly, F508 deletion was also associated with CP and idiopathic CP risk in subgroup analysis stratified by aeitiology, using the fixed effects model. Conclusions Based on current evidence, F508 deletion is a risk factor for CP, and Indians with F508 deletion have much higher CP morbidity. [ABSTRACT FROM AUTHOR]

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 1,112 Han Chinese idiopathic chronic pancreatitis (ICP) patients-the largest ICP cohort so far analyzed in a single population-and 1,580 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 out of 1,112 (1.8%) in patients vs. 24 out of 1,580 (1.52%) in controls; P = 0.57] or functionally impaired variants [three out of 1,112 (0.27%) in patients vs. two out of 1,580 (0.13%) in controls; P = 0.68] were considered. [ABSTRACT FROM AUTHOR]

There is a wide variation in the clinical presentation of chronic pancreatitis (CP) in the different parts of India. Data regarding the clinical profile of CP from eastern India are scarce. We describe the clinical and demographic profiles of patients with CP in eastern India. Consecutive patients were evaluated for the clinical presentation, etiology and complication of CP. One hundred and thirty-nine patients with CP (mean age 39.57±14.88 years; M/F 3.48:1) were included. Idiopathic CP (50.35%) was the most common etiology followed by alcohol (33.81%); 68.34% had calcific CP and 31.65% had noncalcific CP. The median duration of symptoms was 24 (1-240) months. Pain was the most common symptom, being present in 93.52% of the patients. Diabetes, steatorrhea and pseudocyst were present in 45.32%, 14.38% and 7.19% of the cases, respectively. Moderate to severe anemia was revealed in 16.53% of the patients. Benign biliary stricture was diagnosed in 19.42% of the cases (symptomatic in 6.47%). The common radiological findings were the following: pancreatic calculi (68.34%), dilated pancreatic duct (PD) (58.99%), parenchymal atrophy (25.89%) and PD stricture (23.74%). In our center, idiopathic CP followed by alcoholic CP was the most frequent form of CP. Tropical CP was distinctly uncommon. [ABSTRACT FROM AUTHOR]

Background and Aims: Chronic pancreatitis (CP) is a fibroinflammatory syndrome of the pancreas associated with pain and poor quality of life. It has toxic and genetic risk factors but can also be idiopathic. The natural history of idiopathic CP (ICP) is not well-known. Therefore, we studied clinical characteristics and outcomes of these patients followed in our Pancreas Center., Methods: Review of CP patients between January 1, 2016, and April 30, 2021. Patients were divided into 2 groups based on diagnosis, ICP vs non-ICP. CP patients with a smoking history were placed in the non-ICP group. Statistical analysis was performed to identify differences in demographics, comorbidities, complications, controlled medications, and resource utilization., Results: Out of 450 patients, 101 (22%) were diagnosed with ICP and 349 (78%) were non-ICP. ICP patients were mainly female (59.4% vs 40.5%; P  = .005), had less comorbid anxiety (10.5% vs 22.1%; P  = .002), depression (24.2% vs 35.8%; P < .001), disability (13% vs 16.3%; P  = .021), exocrine pancreatic insufficiency (45.3% vs 62.6%; P  = .004), splanchnic vein thrombosis (1.04% vs 14.9%; P < .001), pseudocysts (16.7% vs 41.6%; P < .001), and biliary obstruction (3.12% vs 19.2%; P < .001). They underwent less abdominal imaging (2.63 vs 3.42; P  = .048) and endoscopic retrograde cholangiopancreatography (0.88 vs 1.32; P  = .030). They also had less opioid use (29.6% vs 54.4%; P < .001), gabapentinoid use (34% vs 52.3%; P  = .002), and celiac blocks (7.22% vs 16.1%; P < .041)., Conclusion: Our study demonstrates that the clinical course of ICP is less morbid compared to non-ICP. This study specifically removes smoking, a significant risk factor for CP, to study a truly idiopathic cohort., (© 2023 The Authors.)

Abstract: Background: 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+2T>C 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. Methods: 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. Results: The serine protease inhibitor Kazal type 1 c.194+2T>C 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+2T>C 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+2T>C mutation (p <0.001). In addition, the mean age of diabetes onset in patients with the serine protease inhibitor Kazal type 1 c.194+2T>C mutation (38.33±9.50) was significantly younger than that of patients without this mutation (49.67±6.74). Conclusions: The presence of the serine protease inhibitor Kazal type 1 c.194+2T>C mutation seems to be associated with idiopathic chronic pancreatitis and could predispose individuals to pancreatic diabetes onset at an earlier age. [Copyright &y& Elsevier]

Chronic pancreatitis (CP) has been considered an intractable inflammatory disease that is progressive and irreversible after definite structural changes appear in the pancreas. The Japanese diagnostic criteria for CP were revised in 2009. One of the reasons for this revision was to define a diagnostic criterion for the early phase of CP (early CP) to improve a patient's clinical outcome, because the disease progression might be reversed in this phase by a therapeutic intervention. However, the clinical features and outcome of early CP remain largely unknown, and the diagnostic reliability of early CP needs to be verified. Here, we show two patients who met the diagnostic criteria of early CP and then progressed to the advanced, late phase of CP (definite CP). A 64-year-old man with recurrent acute pancreatitis was diagnosed as early CP and later progressed to definite CP with multiple pancreatic calcifications at the age of 69. The etiology of CP in this patient was thought to be idiopathic. The other patient was a 57-year-old man with alcohol abuse (ethanol consumption > 120 g/day). He was diagnosed as early CP and then rapidly progressed to definite CP without any acute attack. He could not remain abstinent after the diagnosis of early CP. In the present report, we retrospectively demonstrated distinct clinical features of the two patients, both of whom were diagnosed as early CP first and then progressed to definite CP. Thus, our findings support the disease concept of early CP and also suggest the validity of the revised Japanese criteria for the diagnosis of early CP. [ABSTRACT FROM AUTHOR]

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 < 0.001). The frequency of PRSS1 mutation was present in 21.4% of ICP patients, which was significantly higher (p < 0.05) than in controls. Overall, six (18%) SPINK1 mutations in ACP group have been detected. Among 14 patients with ICP, in four (28.6%) of them SPINK1 has been detected. The same mutations have also been found in three (6.5%) control subjects. The frequency of the N34S mutation was higher in patients with ICP than in the controls (p < 0.05), but the frequency of N34S mutation did not differ between ACP and the control group. No relations have been detected between PRSS1 and SPINK1 mutations presence and clinical course and complications of CP.Conclusions: Those preliminary data suggest the high prevalence of SPINK1 and PRSS1 mutations in the Polish population, generally, as well as in CP patients. It may be speculated that those mutations contribute to the development of chronic pancreatitis, especially in patients with alcohol overindulgence. [ABSTRACT FROM AUTHOR]

Idiopathic pancreatitis is diagnosed in up to 25% of patients with chronic pancreatitis by exclusion of other potential causes including rare ones. It has been shown that idiopathic pancreatitis comprises two clinically distinct entities characterised as early-onset and late-onset disease and that the natural courses of both forms differ from that of alcoholic chronic pancreatitis. Due to considerable progress in our understanding of hereditary and autoimmune mechanisms for development of chronic pancreatitis, a specific aetiology of chronic pancreatitis can be determined in an increasing proportion of cases. Nevertheless, the aetiopathogenesis of idiopathic chronic pancreatitis frequently remains obscure. This review focuses on the pathogenetic relevance of various endogenous and exogenous (co-)factors for the manifestation and the natural course of the disease. Moreover, it presents a multifactorial model for understanding the development of idiopathic chronic pancreatitis. [Copyright &y& Elsevier]

Mutations in cystic fibrosis transmembrane conductance regulator ( CFTR) gene have been reported in patients with chronic pancreatitis. The authors examine whether the mutations and haplotypes of CFTR will increase the risk of developing idiopathic chronic pancreatitis (ICP) in Chinese and their genotype and phenotype correlations. Seventy-eight patients with ICP and 200 geographically and ethnically matched controls in Taiwan were analyzed. The entire 27 coding and intronic regions of the CFTR gene were identified using heteroduplex analytical techniques and confirmed by sequencing analysis. The presence of 125G/C, 1001+10C>T, IVSTn(TG)m, 1540A>G, c2694T>G, and c4521G>A were determined by directing sequencing. Abnormal CFTR allele was found to be thrice as frequent in ICP patients as in controls (22/156 vs 19/400, p < 0.0001). T5 allele was associated with early onset of ICP. In six-loci haplotype analysis, 13 common haplotypes were assembled in the 278 individuals tested. The 125G/1001+11C/TG12/470M/2694T/4521G haplotype was associated with risk of ICP (odds ratio 11.3; 95% confidence interval 2.3–54.6, p = 0.008) in Chinese. The mutation spectrum is different from other ethnic groups. A population-specific panel of CFTR changes should be recommended for targeted populations including ICP in Chinese. It is important to design suitable screening programs for different populations. [ABSTRACT FROM AUTHOR]

Abstract: We report an interesting case of a patient with neither family nor personal history for pancreatic diseases that was admitted to our department in 1982, at the age of 25 years. At that time, medical history, absence of alcohol abuse, and radiological imaging suggested a diagnosis of idiopathic chronic pancreatitis. The patient underwent a left-pancreatectomy, with histological confirmation of chronic pancreatitis. He was asymptomatic until 1988, when episodes of pain arose, requiring a pancreatico-jejunostomy. No further problems ensued until 2004 when radiological investigation following pain-related symptoms revealed enormous dilation of the pancreatic duct. A pylorus-preserving pancreaticoduodenectomy resulting in total pancreatectomy was performed. Histological examination revealed an intraductal papillary mucinous non-invasive carcinoma. Review of the previously resected specimen revealed former misdiagnosis. This tumour usually affects an elderly population and nowadays is recognised as a possible cause of chronic obstructive pancreatitis. This report represents a slippery case of misdiagnosis and demonstrates that follow-up is always mandatory following a diagnosis of idiopathic chronic pancreatitis. [Copyright &y& Elsevier]

Several genetic factors have been well known to predispose one to chronic pancreatitis (CP). However, little is known about the genetic factors that may provide a protective effect against the disease. Having found a nonsense mutation (c.111C > A; Y37X) and a splicing mutation (IVS2 + 1G > A) in the cationic trypsinogen gene (protease, serine, 1; PRSS1) in alcoholics without the development of CP, but not in alcoholics with CP and patients with hereditary or idiopathic CP, we propose that while “gain of function” mutations in the PRSS1 gene predispose one to pancreatitis, “loss of function” mutations in the gene may protect one against the disease. [Copyright &y& Elsevier]

Objective: The carboxyl-ester lipase (CEL) gene contains a variable number of tandem repeats (VNTR) region. It remains unclear whether the number of repeats in the CEL VNTR is related to the risk of pancreatic diseases. The aim of this study was to investigate whether CEL VNTR length is associated with idiopathic chronic pancreatitis (ICP), alcoholic chronic pancreatitis (ACP), or pancreatic cancer in a cohort of Chinese patients., Methods: CEL VNTRs were genotyped in patients diagnosed with ICP (n = 771), ACP (n = 222), or pancreatic cancer (n = 263), and in healthy controls (n = 927). CEL VNTR lengths were determined using a screening method combining PCR and DNA fragment analysis., Results: Overall, the CEL VNTR lengths ranged from 5 to 22 repeats, with the 16-repeat allele ('normal' size, N) accounting for 73.82% of all observed alleles. The VNTR allele frequencies and genotype distributions were not significantly different between healthy controls and patients with ACP or pancreatic cancer. For the ICP group, allele frequencies did not differ significantly from the controls, while the frequency of the SS genotype (homozygosity for 5-15 repeats) was significantly higher in the patients (4.67%) than in the controls (1.94%) (p = 0.0014; OR = 2.47; 95% CI = 1.39-4.39)., Conclusions: There were no associations between the CEL VNTR length and ACP or pancreatic cancer. However, homozygosity for short VNTR lengths may confer susceptibility to ICP., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Abstract 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.