Onset Of Chronic Pancreatitis Research Articles

Long-term clinical outcomes of extracorporeal shockwave lithotripsy and endoscopic retrograde cholangiopancreatography for pancreatic duct stone treatment in patients with chronic pancreatitis.

Extracorporeal shock wave lithotripsy for pancreatic stones (P-ESWL) and endoscopic retrograde cholangiopancreatography (ERCP) are the preferred therapeutic approaches for painful chronic pancreatitis (CP) with pancreatic stones. This study aimed to report the short- and long-term outcomes following P-ESWL and ERCP in a large cohort with CP. Patients with painful CP and pancreatic stones >5 mm in size, who underwent P-ESWL and subsequent ERCP between March 2011 and June 2018, were included in this retrospective-prospective mixed observational study. The total stone clearance rates were recorded. All patients were followed up until the end of March 2024, with the visual analogue scale (VAS) for pain, pain type, quality-of-life scores and other relevant information recorded. A total of 2071 patients underwent P-ESWL, and 93.1% of them subsequently underwent ERCP during the study period. Patients were followed up for an average of 11.8 years from the onset of CP and 6.7 years from the first P-ESWL procedure. Complete stone clearance was achieved in 73.7% of the patients. At the end of the follow-up period, 70.1% of the patients achieved complete pain remission. Significant pain type conversion and lower VAS scores were observed in the patients after treatment. Quality-of-life scores and body mass indices increased after P-ESWL and ERCP. P-ESWL and ERCP are effective and minimally invasive treatments for pancreatic stones in patients with painful CP. Most patients achieved complete pain relief, and pain-type conversion was common after treatment. (ClinicalTrials.gov: NCT05916547).

Post-pancreatitis diabetes mellitus is common in chronic pancreatitis and is associated with adverse outcomes.

Post-pancreatitis diabetes mellitus (PPDM) is a common consequence of chronic pancreatitis (CP). We aimed to determine the incidence and predictors of PPDM after CP onset, as well as complications and antidiabetic therapy requirements, in a high-volume tertiary center. We did a cohort study with retrospectively collected data from patients with definite CP seen at the Karolinska University Hospital between January 1999 and December 2020. Cause-specific Cox regression analysis was used to assess PPDM predictors. To estimate risk of complications and need for therapy the Fine-Gray subdistribution hazard model was employed, accounting for death as a competing risk. We identified 481 patients with CP. The cumulative incidence of PPDM was 5.1%, 13.2%, 27.5% and 38.9% at 5, 10, 15 and 20years, respectively. Compared to CP patients without diabetes, patients with PPDM were predominantly male (55% vs. 75%), had more frequently alcoholic etiology (44% vs. 62%) and previous acute pancreatitis. The only independent predictor of PPDM was presence of pancreatic calcifications (aHR=2.45, 95% CI 1.30-4.63). Patients with PPDM had higher rates of microangiopathy (aSHR=1.59, 95% CI 1.02-2.52) and infection (aSHR=4.53, 95% CI 2.60-9.09) compared to CP patients who had type 2 diabetes (T2DM). The rate of insulin use was three-fold higher, whereas metformin use rate was two-fold higher in the same comparison. Patients with PPDM have a higher frequency of clinically significant complications and were more commonly prescribed insulin and metformin, suggesting a more aggressive phenotype than that of T2DM. Greater PPDM awareness is needed to optimize disease management.

Arecae pericarpium water extract alleviates chronic pancreatitis by deactivating pancreatic stellate cells.

Chronic pancreatitis (CP) is a chronic inflammatory disease of the pancreas with irreversible morphological changes. Arecae pericarpium (ARP), known to improve gastrointestinal disorders, has not yet been reported to inhibit fibrosis in CP. Therefore, we investigated the beneficial effects of ARP on cerulein-induced CP. Cerulein (50 μg/kg) was administered intraperitoneally to mice every hour, six times a day, four times a week for a total of 3 weeks to induce CP. To ascertain the prophylactic effects of ARP, ARP water extract (50, 100, or 200 mg/kg) or saline was administered intraperitoneally 1 h before the onset of CP. To determine the therapeutic effects of ARP, ARP water extract (200 mg/kg) or saline was administered for a total of 1 week or 2 weeks, starting 2 weeks or 1 week after the onset of CP. The pancreas was collected immediately for histological analysis. Additionally, to determine the effectiveness and mechanism of ARP in alleviating pancreatic fibrosis, pancreatic stellate cells (PSCs) were isolated. ARP treatment considerably improved glandular atrophy and inflammation and repressed collagen deposition in the pancreas. Furthermore, ARP water extract inhibited extracellular matrix (ECM) constituents such as alpha-smooth muscle actin (α-SMA), collagen I, and fibronectin 1 (FN1) in pancreatic tissue and PSCs. ARP also suppressed transforming growth factor-β (TGF-β) signaling by inhibiting Smad2 phosphorylation. Our study suggests that ARP exhibits anti-fibrotic effects in cerulein-induced CP by inhibiting TGF-β/Smad signaling.

Clinical characteristics of smoking-related chronic pancreatitis.

ObjectiveThe pathogenesis of chronic pancreatitis (CP) is not completely clear. With further studies, smoking is toxic to the pancreas. This study classified smoking-related CP as a new etiology of CP and defined the cutoff of smoking.DesignPatients with CP admitted from January 2000 to December 2013 were included in the study. The characteristics were compared between smoking patients, drinking patients, and a group of patients who never smoke or drink (control group). The cumulative rates of steatorrhea, diabetes mellitus (DM), pancreatic pseudocyst (PPC), pancreatic stone, and biliary stricture after the onset of CP were calculated, respectively.ResultsA total of 1,324 patients were included. Among them, 55 were smoking patients, 80 were drinking patients, and 1,189 were controls. The characteristics of smokers are different from the other two groups, especially in age at the onset and diagnosis of CP, initial manifestation, and type of pain. The development of DM (P = 0.011) and PPC (P = 0.033) was significantly more common and earlier in the smokers than in the other two groups. Steatorrhea also developed significantly more in the smokers than in the controls (P = 0.029). Smokers tend to delay the formation of pancreatic stones and steatorrhea.ConclusionThe clinical characteristics of smoking-related CP is different from CP of other etiologies. A new type of CP, smoking-related CP, was put forward. Smoking-related CP should be separated from idiopathic CP and defined as a new independent subtype of CP different from alcoholic CP or idiopathic CP.

A Classification Algorithm for Types of Diabetes in Chronic Pancreatitis Using Epidemiological Characteristics: Outcome of a Longitudinal Cohort Study.

We developed an epidemiological algorithm to classify types of diabetes mellitus (DM) in chronic pancreatitis (CP), and applied it to a nationwide prospective longitudinal cohort of CP patients. Patients with definite CP (M-ANNHEIM criteria) were classified as having DM types 1, 2, or 3c, or no DM using an algorithm based on epidemiological characteristics: DM onset in relation to age, CP onset, exocrine insufficiency. Variables associated with development of DM were identified. Of 1130 included patients with CP between 2011 and 2018, 368 patients (33%) had DM at inclusion. Among patients with DM, 11 were classified as having type 1 (3%), 159 as type 2 (43%), and 191 as type 3c (52%). Patients with DM type 3c had longer duration of CP, more severe pain and lower physical quality of life. During longitudinal follow-up of median 47 months, 120 (20%) patients developed DM, of which 99 patients were classified as type 3c. This was independently associated with pancreatic endoscopy and surgery. The described algorithm based on epidemiological characteristics can help to classify types of DM in patients with CP. Diabetes mellitus type 3c is associated with longer duration of CP and more severe CP sequelae.

The Impacts of Genetic and Environmental Factors on the Progression of Chronic Pancreatitis

Both environmental factors, such as alcohol consumption and smoking, and genetic factors are strongly associated with the risk of developing chronic pancreatitis (CP). However, comprehensive understanding of their impacts on the progression of CP remains elusive. A prospective cohort study was performed on a large cohort of CP patients with known genetic backgrounds. The cumulative incidence of pancreatic insufficiency after the onset of CP was analyzed using Kaplan-Meier survival curves. Multivariate Cox proportional hazards regression analysis also was performed. A total of 798 patients were enrolled in the study and followed up for 10.5 years. Rare pathogenic genotypes in the SPINK1, PRSS1, CTRC, or CFTR genes were identified in 410 (51.4%) patients. The development of pancreatic insufficiency was significantly earlier in patients with a history of smoking and/or alcohol consumption in both the positive (P < .001) and negative (P= .001) gene mutation groups. However, the development of pancreatic insufficiency did not differ significantly between patients with and without gene mutations despite alcohol and/or smoking status, with P values of .064 and .115, respectively. Multivariate Cox regression analysis showed that age at onset of CP (hazard ratio, [HR], 1.02; P < .001) and alcohol consumption (HR, 1.86; P < .001) were independent risk factors for the development of diabetes, while male sex (HR, 1.84; P= .022) and smoking (HR, 1.56; P= .028) were predictors of steatorrhea. Although rare pathogenic mutations in the 4 major susceptibility genes for CP were not correlated significantly with the development of pancreatic insufficiency, environmental factors (either alcohol consumption or smoking) significantly accelerated disease progression (ClinicalTrials.gov: NCT04574297).

SPINK1 mutations and risk of pancreatic cancer in a Chinese cohort

ObjectiveThe relationship between SPINK1 and pancreatic cancer (PC) remains controversial. The current study aimed to determine the effect of SPINK1 mutations on PC development among patients with chronic pancreatitis (CP). MethodsThis is a prospective observational study including a large cohort of 965 CP patients with 11-year follow-up. Patients’ demographic characteristics and clinical CP outcomes were documented in detail. Genetic testing was performed. The effect of SPINK1 mutations on the clinical development of PC was explored using Cox proportional hazards regression. Subgroup analyses conducted included the consideration of gender, onset age of CP (early- and late-onset), etiologies of CP, smoking, and alcoholic drinking status. ResultsPC was diagnosed in 2.5% (24/965) of patients, and the cumulative incidence rates were 0.2%, 0.8%, and 1.5% at 3, 5, and 10 years since the onset of CP, respectively. In this cohort, SPINK1 c.194+2T > C was the most common variant with a proportion of 39.1%. And the risk of PC development varied marginally between patients with and without SPINK1 mutations (Cox HR 0.39(0.14–1.04), P = 0.059). In the subgroup analyses, patients carrying SPINK1 mutations had a significantly lower risk of PC (Cox HR 0.18(0.04–0.80), P = 0.025) in the non-smoking group. SPINK1 mutations showed no significant effect in the other subgroups considered. ConclusionsCP patients harboring SPINK1 mutations do not have an elevated risk of PC development compared to mutation-negative CP patients. On the contrary, SPINK1 mutations may be a protective factor in non-smoking patients with CP.

Factors associated with prior acute pancreatitis episodes among patients with chronic pancreatitis

BackgroundThe relationship between chronic pancreatitis (CP) and acute pancreatitis (AP) is complex and not well understood. CP could be preceded by antecedent episodes of AP. AimsThe aim of this study was to explore both genetic and environmental factors associated with AP episodes before the diagnosis of CP. MethodsThis was a cross-sectional study including 1022 patients. Detailed demographic, genetic, and clinical data were collected. Based on the presence of AP episode(s) before diagnosis of CP, patients were divided into AP group (further classified into single episode of AP group and recurrent AP group) and non-AP group. Related factors among these groups were assessed using multivariate logistic regression model. ResultsBefore diagnosis of CP, 737 patients (72.1%) had a history of AP. Smoking(P = 0.005) and heavy alcohol consumption(P = 0.002) were risk factors for AP while age at CP onset(P < 0.001), harboring the SPINK1 mutation(P < 0.001), diabetes(P < 0.001) and steatorrhea(P < 0.001) were protective factors. Further, alcoholic CP(P = 0.019) was the only independent risk factor for recurrent AP attacks while age at onset of CP(P < 0.001), pancreatic stones(P = 0.024). and pseudocysts(P = 0.018) served as protective factors. ConclusionsSPINK1 mutations served as protective factor for AP episodes, suggesting SPINK1 mutation might play a pathogenic role in CP occurrence with occult clinical manifestations.

&lt;i&gt;SPINK1&lt;/i&gt; Mutations and Risk of Pancreatic Cancer in Patients with Chronic Pancreatitis: Data from a Prospective Cohort Study

Objective: The relationship between SPINK1 and pancreatic cancer (PC) remains controversial. The current study aimed to determine the effect of SPINK1 mutations on PC development among patients with chronic pancreatitis (CP). Methods: This is a prospective observational study including a large cohort of 965 CP patients with 11-year follow-up. Patients’ demographic characteristics and clinical CP outcomes were documented in detail. Genetic testing was performed, and rare pathogenic variants of SPINK1 were included in the study. The effect of SPINK1 mutations on the clinical development of PC was explored using Cox proportional hazards regression. Subgroup analyses conducted included the consideration of gender, onset age of CP (early- and late-onset), etiologies of CP, smoking, and alcoholic drinking status. Results: PC was diagnosed in 2.5% (24/965) of patients, and the cumulative incidence rates were 0.2%, 0.8%, and 1.5% at 3, 5, and 10 years since the onset of CP, respectively. SPINK1 c.194+2T>C was the most common variant with a proportion of 39.1%. The risk of PC development varied marginally between patients with and without SPINK1 mutations (Cox HR 0.39(0.14-1.04), P=0.059). In the subgroup analyses, patients carrying SPINK1 mutations had a significantly lower risk of PC (Cox HR 0.18(0.04-0.80), P=0.025) in the non-smoking group. SPINK1 mutations showed no significant effect in the other subgroups considered. Conclusions: CP patients harboring SPINK1 mutations do not have an elevated risk of PC development. On the contrary, SPINK1 mutation appears to be a protective factor in non-smoking patients with CP. The exact relationship between SPINK1 mutations and PC warrants further investigation. Funding Statement: Financial support for this study came from the National Natural Science Foundation of China (Grant Nos. 82070661 [W.B.Z.], 81970560[Z.L.], 81873588[Z.S.L.]); Scientific Innovation Program of Shanghai Municipal Education Committee (No. 201901070007E00052); the fund for “Clinical Technology Innovation Project Task (Contract)” of Shanghai Shenkang Hospital Development Center (to ZL, No. SHDC2020CR2032B). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The study was approved by the Ethics Committee of Changhai Hospital.

Chronic pancreatitis: what should be considered in diagnosis, treatment, and prognosis

The aim of the literature review is to draw attention of doctors to the need of considering not only well-known etiological factors, but also pathogenetic ones that have an impact on the progression, chronicity of the process, treatment, prevention, and prognosis.&#x0D; The role of alcohol, mechanism of obstruction of the pancreatic ducts in the occurrence of abdominal pain in chronic pancreatitis, and the development and progression of exocrine pancreatic insufficiency are discussed in detail.The issues of the onset of chronic pancreatitis in elder age, comorbidity with other diseases of the internal organs, with a lack of certain vitamins are considered. It is necessary to remember that exocrine insufficiency can be associated with the progression of glandular fibrosis, metabolic disorders, food intolerance, allergic syndrome, which provoke acute attacks.The author draws attention to the fact that the syndrome of inflammatory, enzymatic intoxication and the syndrome of disseminated intravascular coagulation should not be missed out in the acute nature of the process. Above-listed recommendations will help to correctly evaluate the clinical picture and prescribe the proper treatment, as well as to prevent the development of complicationsin time.

Divergent trends in lifetime drinking and smoking between Black and White Americans diagnosed with chronic pancreatitis

Background/objectivesBlack Americans are at increased risk of chronic pancreatitis (CP) compared to their White counterparts. We aimed to describe the race-specific smoking history and lifetime drinking in patients diagnosed with CP. MethodsWe analyzed data on 334 Black and White CP participants of the North American Pancreatitis Study 2 Continuation and Validation Study and Ancillary Study. Lifetime drinking history and lifetime smoking history were collected through in-person interviews. Intensity, frequency, duration and current status of drinking and smoking were compared between Black and White CP participants, stratified by physician-defined alcohol etiology. In addition, drinking levels at each successive decades in life (20s, 30s, 40s) were compared by race and graphically portrayed as heat diagrams. ResultsAmong patients with alcoholic CP, current smoking levels were not different by race (67–70%), but a smaller proportion of Black patients reported having smoked 1 or more packs per day in the past (32%) as compared to White patients (58%, p < 0.0001). Black patients were more likely to report current consumption of alcohol (31%), as opposed to White patients (17%, p = 0.016). Black patients also reported more intense drinking at age 35 and 45 years as compared to White patients, while age at CP onset were similar between the two groups. ConclusionWe found more intense drinking but less intense smoking history in Black CP patients as compared to White CP patients. Effective alcohol abstinence and smoking cessation program with sustained impact are needed in CP patients.

Association between chronic pancreatitis and pancreatic cancer: A 10-year retrospective study of endoscopically treated and surgical patients.

Pancreatic cancer (PC) has a poor prognosis. Chronic pancreatitis (CP) associates with high morbidity and mortality, and serves as a risk factor for PC. Our study aimed to assess the association between endoscopically treated CP patients and PC, and to establish the rate of CP among patients undergoing surgery for pancreatic ductal adenocarcinoma (PDAC). We retrospectively analyzed 458 CP patients undergoing endoscopic treatment (ET) between 2000 and 2010 and 349 PDAC patients undergoing pancreatic resection between 2000 and 2014 at the Helsinki University Hospital. The likelihood of diagnosing PC was highest within 2 years of a CP diagnosis: 21 of 30 PC diagnoses occurred during this time. After 2 years follow-up: 9 of 30 PC diagnoses occurred 2-12 years from CP diagnosis. Two patients were diagnosed with CP before PDAC. Multivariate analysis showed two prognostic factors indicative of PC development: biliary stricture (HR 9.21; 95% CI 3.76-22.08) and a higher age (per 5-year increases) at CP onset (HR 1.55; 95% CI 1.30-1.85). Among 458 CP patients, the median overall survival without PC was 14.7 years (95% CI 12.0-17.3), falling to 1.6 years (95% CI 1.2-2.0) with PC. The high incidence of PC among CP patients at the beginning of follow-up likely reflected an initially missed PC diagnoses. In long-term follow-up, an increasing PC incidence might reflect the PC-predisposing impact of CP. Thus, we recommend careful follow-up for patients presenting with a recently diagnosed CP and risk factors for PC.

Natural course of chronic pancreatitis and predictors of its progression

BackgroundThe natural course of chronic pancreatitis(CP) and its complications has been inadequately explored. We aimed to describe the natural history and factors affecting the progression of alcoholic(ACP), idiopathic juvenile(IJCP) and idiopathic senile(ISCP) variants of CP. MethodsThis study was a retrospective analysis from a prospectively maintained database of patients with CP following up at a tertiary care centre from 1998 to 2019. Cumulative rates of pain resolution, diabetes, steatorrhea, pseudocysts and pancreatic cancer were computed using Kaplan-Meier analysis, and the factors affecting their incidence were identified on multivariable-adjusted Cox-proportional-hazards model. ResultsA total of 1415 patients were included, with 540(38.1%) ACP, 668(47.2%) IJCP and 207(14.6%) ISCP with a median follow-up of 3.5 years(Inter-quartile range: 1.5–7.5 years). Diabetes occurred at 11.5, 28 and 5.8 years(p < 0.001) while steatorrhea occurred at 16, 24 and 18 years(p = 0.004) after onset for ACP, IJCP and ISCP respectively. Local complications including pseudocysts occurred predominantly in ACP(p < 0.001). Ten-year risk of pancreatic cancer was 0.9%, 0.2% and 5.2% in ACP, IJCP and ISCP, respectively(p < 0.001). Pain resolution occurred more frequently in patients with older age of onset[Multivariate Hazard Ratio(HR):1.7(95%CI:1.4–2.0; p < 0.001)], non-smokers[HR:0.51(95%CI:0.34–0.78); p = 0.002] and in non-calcific CP[HR:0.81(0.66–1.0); p = 0.047]. Occurrence of steatorrhea[HR:1.3(1.03–1.7); p = 0.028] and diabetes[HR:2.7(2.2–3.4); p < 0.001] depended primarily on age at onset. Occurrence of pancreatic cancer depended on age at onset[HR:12.1(4.7–31.2); p < 0.001], smoking-history[HR:6.5(2.2–19.0); p < 0.001] and non-alcoholic etiology[HR:0.14(0.05–0.4); p < 0.001]. ConclusionACP, IJCP and ISCP represent distinct entities with different natural course. Age at onset of CP plays a major prognostic role in all manifestations, with alcohol predominantly causing local inflammatory complications.

Risk Factors and Nomogram for Pancreatic Stone Formation in Chronic Pancreatitis over a Long-Term Course: A Cohort of 2,153 Patients

Background: Pancreatic stones are pathognomonic of chronic pancreatitis (CP). This study aimed to determine the incidence, identify risk factors, and develop a nomogram for pancreatic stones in CP patients. Methods: Patients with CP admitted to our center from January 2000 to December 2013 were enrolled. Cumulative rates of pancreatic stones after the onset of CP and after the diagnosis of CP were calculated. Patients were randomly assigned, in a 2:1 ratio, to the training and validation cohort. Based on the training cohort, risk factors 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: With a total of 2,153 CP patients, pancreatic stones were detected in 1,626 (75.5%) patients, with a median follow-up of 7.8 years. Age at the onset of CP, body mass index, smoking, diabetes mellitus, pancreatic pseudocyst, biliary stricture, severe acute pancreatitis, and type of pain were identified risk factors for pancreatic stones development. The nomogram with these 8 factors achieved good accuracy. Conclusions: The nomogram achieved an individualized prediction of pancreatic stones development in CP. It may help the management of pancreatic stones.

Combination of intravenous hydration and indomethacin suppository is the most effective therapy for the prevention of post-ERCP pancreatitis – A network meta-analysis

It has previously been reported in a European case-control study with patients from Germany and France that CEL-HYB1, a hybrid allele of the carboxyl ester lipase (CEL) gene and its pseudogene CELP, increases susceptibility to chronic pancreatitis (CP). Here, we aimed to replicate this finding in Polish pediatric patients with CP.The distribution of the CEL-HYB1 allele in a CP pediatric cohort (n = 147, median age at CP onset 7.6 years) with no history of alcohol/smoking abuse was compared with ethnically matched healthy controls (n = 500, median age 46 years). Screening was performed using long-range PCR followed by agarose gel-electrophoresis.We observed no significant difference in the carrier frequency of the CEL-HYB1 allele between CP patients (7/147, 4.8%) and controls (12/500, 2.4%; P = 0.16).This study found no statistically significant association between CEL-HYB1 and chronic pancreatitis in a cohort of Polish pediatric CP patients.

Video-assisted Retroperitoneal Debridement (VARD) in infected necrotizing pancreatitis – 12 year experience in the Netherlands

It has previously been reported in a European case-control study with patients from Germany and France that CEL-HYB1, a hybrid allele of the carboxyl ester lipase (CEL) gene and its pseudogene CELP, increases susceptibility to chronic pancreatitis (CP). Here, we aimed to replicate this finding in Polish pediatric patients with CP.The distribution of the CEL-HYB1 allele in a CP pediatric cohort (n = 147, median age at CP onset 7.6 years) with no history of alcohol/smoking abuse was compared with ethnically matched healthy controls (n = 500, median age 46 years). Screening was performed using long-range PCR followed by agarose gel-electrophoresis.We observed no significant difference in the carrier frequency of the CEL-HYB1 allele between CP patients (7/147, 4.8%) and controls (12/500, 2.4%; P = 0.16).This study found no statistically significant association between CEL-HYB1 and chronic pancreatitis in a cohort of Polish pediatric CP patients.

The hybrid allele 1 of carboxyl-ester lipase (CEL-HYB1) in Polish pediatric patients with chronic pancreatitis

ObjectivesIt has previously been reported in a European case-control study with patients from Germany and France that CEL-HYB1, a hybrid allele of the carboxyl ester lipase (CEL) gene and its pseudogene CELP, increases susceptibility to chronic pancreatitis (CP). Here, we aimed to replicate this finding in Polish pediatric patients with CP. MethodThe distribution of the CEL-HYB1 allele in a CP pediatric cohort (n = 147, median age at CP onset 7.6 years) with no history of alcohol/smoking abuse was compared with ethnically matched healthy controls (n = 500, median age 46 years). Screening was performed using long-range PCR followed by agarose gel-electrophoresis. ResultsWe observed no significant difference in the carrier frequency of the CEL-HYB1 allele between CP patients (7/147, 4.8%) and controls (12/500, 2.4%; P = 0.16). ConclusionsThis study found no statistically significant association between CEL-HYB1 and chronic pancreatitis in a cohort of Polish pediatric CP patients.

Risk Factors and Nomogram for Common Bile Duct Stricture in Chronic Pancreatitis: A Cohort of 2153 Patients.

To identify the risk factors and develop nomograms for common bile duct (CBD) stricture in chronic pancreatitis (CP) patients. CBD stricture is a common complication in CP and has a variable clinical presentation ranging from asymptomatic to overt jaundice and cholangitis. Patients with CP admitted to Changhai Hospital (Shanghai, China) from January 2000 to December 2013 were enrolled. Cumulative rates of CBD stricture after onset and diagnosis of CP were calculated. Patients were randomly assigned, in a 2:1 ratio, to the training and validation cohort. On the basis of the training cohort, risk factors for CBD stricture and symptomatic CBD stricture were identified through Cox proportional hazards regression model, and nomograms was developed, respectively. Internal and external validations were performed based on the training and validation cohort, respectively. With a total of 2153 patients, the median duration of follow-up was 7.0 years. CBD strictures were detected in 340 (15.8%) patients, whereas 159 of them were symptomatic. Male gender, age at onset of CP, smoking, body mass index, and morphology of main pancreatic duct were identified risk factors for CBD stricture development. Age at onset of CP, body mass index, and type of pain were identified risk factors for symptomatic CBD stricture development. Both nomograms achieved good concordance indexes with well-fitted calibration curves. The nomogram achieved an individualized prediction of symptomatic CBD stricture development in CP patients. It may help the early diagnosis and intervention of symptomatic CBD stricture and reduce the rates of severe adverse events.

Risk factor for steatorrhea in pediatric chronic pancreatitis patients

BackgroundPediatric patients always suffer from chronic pancreatitis (CP), especially those with steatorrhea. This study aimed to identify the incidence of and risk factors for steatorrhea in pediatric CP. To our best knowledge, there is no pediatric study to document the natural history of steatorrhea in CP.MethodsCP patients admitted to our center from January 2000 to December 2013 were enrolled. Patients were assigned to the pediatric (< 18 years old) and adult group according to their age at onset of CP. Cumulative rates of steatorrhea in both groups were calculated. Risk factors for both groups were identified, respectively.ResultsThe median follow-up duration for the whole cohort was 7.6 years. In a total of 2153 patients, 13.5% of them were pediatrics. The mean age at the onset and the diagnosis of CP in pediatrics were 11.622 and 19.727, respectively. Steatorrhea was detected in 46 patients (46/291, 15.8%) in the pediatric group and in 447 patients (447/1862, 24.0%) in the adult group. Age at the onset of CP (hazard ratio [HR], 1.121), diabetes mellitus (DM, HR, 51.140), and severe acute pancreatitis (SAP, HR, 13.946) was identified risk factor for steatorrhea in the pediatric group.ConclusionsAge at the onset of CP, DM and SAP were identified risk factors for the development of steatorrhea in pediatric CP patients. The high-risk populations were suggested to be followed up closely. They may benefit from a full adequate pancreatic exocrine replacement therapy.

SPINK1, PRSS1, CTRC, and CFTR Genotypes Influence Disease Onset and Clinical Outcomes in Chronic Pancreatitis.

ObjectivesRare pathogenic variants in the SPINK1, PRSS1, CTRC, and CFTR genes have been strongly associated with a risk of developing chronic pancreatitis (CP). However, their potential impact on the age of disease onset and clinical outcomes, as well as their potential interactions with environmental risk factors, remain unclear. These issues are addressed here in a large Chinese CP cohort.MethodsWe performed targeted next-generation sequencing of the four CP-associated genes in 1061 Han Chinese CP patients and 1196 controls. To evaluate gene–environment interactions, the patients were divided into three subgroups, idiopathic CP (ICP; n = 715), alcoholic CP (ACP; n = 206), and smoking-associated CP (SCP; n = 140). The potential impact of rare pathogenic variants on the age of onset of CP and clinical outcomes was evaluated using the Kaplan–Meier model.ResultsWe identified rare pathogenic genotypes involving the SPINK1, PRSS1, CTRC, and/or CFTR genes in 535 (50.42%) CP patients but in only 71 (5.94%) controls (odds ratio = 16.12; P < 0.001). Mutation-positive patients had significantly earlier median ages at disease onset and at diagnosis of pancreatic stones, diabetes mellitus and steatorrhea than mutation-negative ICP patients. Pathogenic genotypes were present in 57.1, 39.8, and 32.1% of the ICP, ACP, and SCP patients, respectively, and influenced age at disease onset and clinical outcomes in all subgroups.ConclusionsWe provide evidence that rare pathogenic variants in the SPINK1, PRSS1, CTRC, and CFTR genes significantly influence the age of onset and clinical outcomes of CP. Extensive gene–environment interactions were also identified.