To evaluate temporal trends in gender, etiology, severity, outcomes, cost and median length of stay (MLS) in patients with acute pancreatitis (AP) in a third-tier Chinese city.

Patients with AP admitted to a university hospital between January 2013 and December 2021. Relationships between etiology, prevalence of severe acute pancreatitis (SAP) and survey years were investigated by joinpoint regression analysis.

A total of 5459 (male 62.3%) patients with AP were included. Between January 2013 and December 2021, we observed: (a) the prevalence of biliary diseases-related AP was stable, while the prevalence of hypertriglyceridemia (HTG)-associated AP (Ptrend = 0.04) and alcohol-associated AP (Ptrend < 0.0001) both increased; (b) there was an increase in crude prevalence of SAP from 4.97% to 12.2% between 2013 and 2021 (Ptrend < 0.0001); (c) compared to female populations, male gender had a higher prevalence of AP; (d) there was a decrease in MLS from 11 days to 8 days (Ptrend < 0.0001) and in median cost of hospitalization (MCH) for all patients (from 20,166 to 12,845 YUAN) (Ptrend < 0.0001); (e) the overall in-hospital mortality rate was 1.28% (70/5459) for patients with AP. There was no statistically significant in the time trend of mortality during the study period (Ptrend = 0.5873). At multivariate analysis, survey year was associated with prevalence of SAP after adjustment by age and biliary diseases (OR: 1.07; 95% CI: 1.03-1.12). Based on the stratification by severity of disease, the decrease of MLS and MCH was more significant in non-SAP vs. SAP patients.

Over the observational period, the proportion of male patients with AP, prevalence of age-adjusted rate of HTG and alcohol-associated AP and SAP increased, while MLS and MCH for all patients decreased, and the time trend of mortality of AP was stable.

Diagnosis of chronic pancreatitis (CP) is invasive and depending on endoscopic ultrasound (EUS) evaluation using Rosemont Criteria (RC). Non invasive ultrasound (US) based tests are necessary to detect CP.

We compared transabdominal 2D Shear Wave Elastography (SWE) of the pancreas and the Gemelli Ultrasound Chronic Pancreatitis Score to EUS/RC for the diagnosis of chronic pancreatitis.

We conducted a single center prospective case-control study. EUS with RC defined cohorts with (n = 51) and without CP (n = 51). Patients underwent US evaluation of the pancreas using 2D SWE and USCP.

Median SWE values were different between groups (no CP 1.45m/s; IQR 1.34-1.60 and with CP 1.72m/s; IQR 1.63-1.96; p < 0.0001) and different between RC subgroups (RC indeterminate for CP 1.67m/s, IQR 1.52-1.72 vs. RC suggestive 1.72m/s, IQR 1.62-1.97 vs. RC consistent with CP 1.90 m/s, IQR 1.72-2.12 m/s; p < 0.0001). Median USCP was different between groups. 2D SWE correlated with USCP (p < 0.0001) and RC (p < 0.0001). We defined a cut off SWE value of <1.42m/s to rule out CP (Sensitivity 96 %; NPV 92 %) and a SWE cut off >1.87m/s to diagnose CP (Specifity 96 %;PPV 90 %).

Pancreatic US evaluation with 2D SWE is a widely applicable and unexpensive tool for the diagnosis of CP. Larger studies are needed to confirm these results.

Activation of type M2 macrophages has been implicated in the pathogenesis of chronic pancreatitis (CP). In a clinical pilot study, we investigated blood-based markers of macrophage activation at different stages of CP.

We performed a cross-sectional analysis of prospectively collected plasma samples from healthy controls and patients with suspected or definitive CP according to the M-ANNHEIM criteria. Plasma concentrations of soluble CD163 (sCD163), soluble CD206 (sCD206), and monocyte chemoattractant protein-1 (MCP-1) were analyzed using enzyme-linked immunosorbent assays. Group and pairwise comparisons of analytes were performed using regression models and area under the receiver operating curves (AUC-ROC).

In total, 73 subjects with CP (28 suspected CP and 45 definitive CP) and 40 controls were included. Compared to controls, the median plasma concentrations of sCD163 ( P  = 0.019) and sCD206 ( P  = 0.033) were elevated in patients with definitive CP. sCD206 was also elevated in patients with definitive CP ( P  = 0.042) compared to suspected CP. ROC analysis revealed the optimal sCD163 cutpoint to distinguish definitive CP from controls was 1.84 mg/mL (AUC-ROC 0.65; 95% confidence interval [CI], 0.54-0.77). The optimal sCD206 cutpoint to distinguish definitive CP from controls was 0.24 mg/mL (AUC-ROC 0.66; 95% CI, 0.54-0.78). MCP-1 concentrations showed no differences across subgroups.

Our study demonstrates that subjects with definitive CP, sampled during a clinically quiescent phase, exhibited increased levels of sCD163 and sCD206. This indicates the presence of activated M2 macrophages in patients with CP at advanced, but not early, clinical stages.

This review examines current research on healthcare disparities in pancreatitis, identifies knowledge gaps, and proposes strategies to develop targeted multilevel interventions to address inequities in pancreatitis care.

Current literature has identified patient, disease, and healthcare-level factors contributing to disparities in risk factors and health outcomes of pancreatitis. Moreover, social structures, economic systems, social vulnerability, and policy significantly influence the pancreatitis care continuum.

Understanding the root causes of health inequities is critical to developing effective approaches for the prevention, early detection, and management of pancreatitis.

Acute pancreatitis, among the most prevalent gastrointestinal disorders, exhibits a continual rise in its incidence recent years. This study endeavor to explore the correlation between smoking exposure and the severity of acute pancreatitis (AP).

Five hundred and eight patients diagnosed as acute pancreatitis (AP) were included in our data analysis. Patients were categorized based on their smoking pack-years into four groups: light, moderate, heavy, and non-smokers. Outcomes were classified as two: "mild acute pancreatitis (MAP)" and "moderately severe acute pancreatitis (MSAP) or severe acute pancreatitis (SAP)". We conducted propensity score matching (PSM) to adjust confounding factors and multivariable logistic regression analysis to determine adjusted odds ratios and 95% confidence intervals. Additionally, a dose-dependent association analysis between smoking exposure and the incidence rate of "MSAP or SAP" was performed.

Smokers exhibited a higher risk of "MSAP or SAP" compared to non-smokers, both before (17.1 vs. 54.9%, p < 0.001) and after (9.4 vs. 24.7%, p < 0.001) PSM. With an area under the ROC curve of 0.708, smoking showed a moderate level of predictive ability. Furthermore, propensity score matching analysis showed that patients who smoked compared to non-smokers had significantly higher risks of "MSAP or SAP" for light smoking (OR 3.76, 95% CI 1.40-10.07, p = 0.008), moderate smoking (OR 4.94, 95% CI 2.23-10.92, p < 0.001), and heavy smoking (OR 8.08, 95% CI 3.39-19.25, p < 0.001).

Smoking is an independent risk factor that can raise the severity of pancreatitis. Moreover, the severity of acute pancreatitis escalates in tandem with the accumulation of pack-years of smoking.

(1) Background: Alcohol consumption is one of the main causes of acute pancreatitis. (2) Material and Methods: In this unicentric retrospective cohort study, we selected 1855 patients from the Bucharest Acute Pancreatitis Index (BUC-API) who presented with acute pancreatitis. We investigated correlations between Alcoholic Acute Pancreatitis (AAP) and the rate of complications, cost, length of hospitalization and rate of recurrence. (3) Results: We found a moderately strong association between AAP and recurrence (p < 0.01) and observed that the disease is likelier to evolve with pseudocysts and walled-off necrosis than other forms of AP. Patients with AAP are less likely to have a morphologically normal pancreas than patients suffering from AP of other causes (p < 0.01), but a low probability of requiring intensive care unit admission (p < 0.01) significantly lowers daily cost (Md = 154.7 EUR compared to Md = 204.4 EUR) (p < 0.01). (4) Conclusions: This study's data show that patients with AAP have a greater rate of pseudocyst occurrence, lower intensive care unit admittance rate and lower cost of hospitalization than patients with AP of other causes. Typical Sketch: A middle-aged male tobacco smoker with recurrent AP, lower risk of in-hospital mortality and complications such as pseudocysts; treated in a gastroenterological ward and discharged at-will.

Diabetes is a major cause of disease burden with considerable public health significance. While the pancreas plays a significant role in glucose homeostasis, the association between pancreatitis and new onset diabetes is not well understood. The purpose of this study was to examine that association using large real-world data.

Utilizing the IBM® MarketScan® commercial claims database from 2016 to 2019, pancreatitis and diabetes regardless of diagnostic category, were identified using International Classification of Diseases, Tenth Revision [ICD-10] codes. We then performed descriptive analyses characterizing non-pancreatitis (NP), acute pancreatitis (AP), and chronic pancreatitis (CP) cohort subjects. Stratified Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) of diabetes across the three clinical categories.

In total, 310,962 individuals were included in the analysis. During 503,274 person-years of follow-up, we identified 15,951 incident diabetes cases. While men and women had higher incidence rates of CP and AP-related diabetes, the rates were significantly greater in men and highest among individuals with CP (91.6 per 1000 persons-years (PY)) followed by AP (75.9 per 1000-PY) as compared to those with NP (27.8 per 1000-PY). After adjustment for diabetes risk factors, relative to the NP group, the HR for future diabetes was 2.59 (95% CI: 2.45-2.74) (P<0.001) for the CP group, and 2.39 (95% CI: 2.30-2.48) (P<0.001) for the AP group.

Pancreatitis was associated with a high risk of diabetes independent of demographic, lifestyle, and comorbid conditions.

Tobacco smoking is a known risk factor for progression of chronic pancreatitis (CP).

We compare clinical outcomes of CP patients with current or former smoking with those who have never smoked.

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.

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).

CP patients who smoke or formerly smoked have greater morbidity and worse outcomes than non-smokers.

In the Asian population, existing studies regarding the association between smoking and acute pancreatitis are few in number. The aim of this study was to investigate the incidence of acute pancreatitis according to smoking habits and smoking habit changes of the Korean population.

We used clinical data from individuals (aged 20 years or older) who received health examinations arranged by the Korean National Health Insurance Service in 2009 (n = 4 238 822) or in 2009 and 2011 (n = 2 617 306). The incidence of acute pancreatitis was analyzed according to smoking status or smoking habit change reported by individuals during their health examination. Newly diagnosed acute pancreatitis was identified using claims data from baseline to the date of diagnosis or until December 31, 2018.

The risk of acute pancreatitis was significantly higher in current smokers compared with never-smokers regardless of age or sex. The adjusted hazard ratio (HR) of acute pancreatitis in current smokers increased according to the amount of smoking (HR 1.28; 95% confidence interval [CI], 1.12-1.45 in <10 cigarettes/day, HR 1.4; CI, 1.3-1.52 in 10-19 cigarettes/day, HR 1.66; CI, 1.55-1.78 in ≥20 cigarettes/day). The adjusted HR of acute pancreatitis in continuous smokers was 1.66 (CI, 1.53-1.8) compared with never-smokers and was higher than smokers who quit smoking (HR 1.34; CI, 1.17-1.54).

In this Korean population-based cohort study, smoking increased the incidence of acute pancreatitis in a dose-dependent manner, and smoking cessation helped decrease the incidence of acute pancreatitis.

Chronic pancreatitis (CP) is a fibroinflammatory disorder that results in irreversible scarring to pancreatic parenchyma and presents with a myriad of symptoms including abdominal pain, nausea, weight loss, steatorrhea, and diabetes. Furthermore, patients with CP often have comorbid chemical dependencies to alcohol and tobacco, which can further complicate the management of CP. Recent literature proposes guidelines on how best to care for patients with CP and establishes requirements for centers of excellence. Here, we review the available data on endoscopic therapies, pain management, chemical dependency, and nutrition for patients with CP and propose quality metrics that may be used to establish a quality practice.

We tested the hypothesis that six toxic risk factors from the TIGAR-O classification system are equally important for risk of chronic pancreatitis, at the level of the individual patient and in the general population. 108,438 women and men aged 20-100 years participating in the Copenhagen General Population Study from 2003 to 2015 were included. Associations of smoking, alcohol intake, waist/hip ratio, kidney function, plasma triglycerides, plasma Ca²⁺, and diseases within the causal pathway with risk of chronic pancreatitis, and corresponding population attributable risks were estimated. Information on chronic pancreatitis was from national Danish health registries. During median 9 years (range: 0-15) of follow-up, 313 individuals had a first diagnosis of chronic pancreatitis; the incidence of chronic pancreatitis per 10,000 person-years were 3.1 overall, 2.8 in women, and 3.5 in men. Of the six toxic risk factors and relative to individuals with low values, individuals in the top 5% had hazard ratios for chronic pancreatitis of 3.1(95% CI 2.1-4.5) for pack-years smoked, 2.5(1.5-4.0) for alcohol intake, and 1.6(1.1-2.6) for plasma triglycerides. Corresponding values versus those without the baseline disease were 12.6 (7.9-20.2) for acute pancreatitis, 1.9 (1.2-2.8) for gallstone disease, and 1.9 (1.3-2.7) for diabetes mellitus. The highest population attributable fractions were for women (1) ever smoking (31%), (2) gallstone disease (5%), and (3) diabetes mellitus (4%), and for men (1) ever smoking (38%), (2) acute pancreatitis (7%)/high alcohol intake (7%), and (3) high plasma triglycerides (5%). Smoking is the most important risk factor for chronic pancreatitis in the general population.

Only 3-5% of heavy alcohol users develop acute alcohol pancreatitis (AAP). This suggests that additional triggers are required to initiate the inflammatory process. Genetic susceptibility contributes to the development of AAP, and SPINK1 mutation is a documented risk factor. We investigated the prevalence of the SPINK1(N34S) mutation in patients with AAP compared to heavy alcohol users who had never suffered an episode of pancreatitis. Blood samples for the mutational analysis from patients with first episode (n = 60) and recurrent AAP (n = 43) and from heavy alcohol users without a history of AAP (n = 98) as well as from a control population (n = 1914) were obtained. SPINK1 mutation was found in 8.7% of the patients with AAP. The prevalence was significantly lower in healthy controls (3.4%, OR 2.72; 1.32-5.64) and very low in alcoholics without pancreatitis (1.0%, OR 9.29; 1.15-74.74). In a comparison adjusted for potential cofounders between AAP patients and alcoholics, SPINK1 was found to be an independent marker for AAP. The prevalence of the SPINK1 mutation is overrepresented in AAP patients and very low in alcoholics without pancreatitis. This finding may play a role in understanding the variable susceptibility to AAP found in heavy alcohol users.

This study aimed to identify the risk factors for the progression of acute pancreatitis (AP) to severe acute pancreatitis (SAP) and death in elderly patients.

This was a single-center retrospective study conducted in a tertiary teaching hospital. Data on patient demographics, comorbidities, duration of hospitalization, complications, interventions, and mortality rates were collected.

Between January 2010 and January 2021, 2084 elderly patients with AP were included in this study. The mean age of the patients was 70.0 years (standard deviation, 7.1 years). Among them, 324 (15.5%) had SAP and 105 died (5.0%). The 90-day mortality rate in the SAP group was significantly higher than that in the AP group (P < 0.0001). Multivariate regression analysis revealed that trauma, hypertension, and smoking were risk factors for SAP. After multivariate adjustment, acute respiratory distress syndrome, acute kidney injury, sepsis, organ perforation, and abdominal hemorrhage were associated with higher 90-day mortality.

Traumatic pancreatitis, hypertension, and smoking are independent risk factors for SAP in elderly patients. Acute respiratory distress syndrome, acute kidney injury, sepsis, organ perforation, and abdominal hemorrhage are independent risk factors for death in elderly patients with AP.

Heavy alcohol consumption and genetic factors represent the 2 major etiologies of chronic pancreatitis (CP). However, little is so far known about the clinical features and genetic basis of light-to-moderate alcohol consumption-related CP (LMA-CP).

A cross-sectional analysis was performed on 1061 Chinese CP patients between 2010 and 2015. CP was classified as classical alcoholic CP (ACP; n = 206), LMA-CP (n = 154), and idiopathic CP (ICP; n = 701). Clinical features and genetic characteristics (PRSS1, SPINK1, CTRC, CFTR variant status) were compared between the different groups. Odds ratios (ORs) with 95% confidence intervals were calculated to ascertain the combinatorial effect of alcohol consumption and gene mutation.

Compared with ICP, the clinical features of LMA-CP were characterized by higher rates of developing pancreatic stones, pseudocyst, diabetes, and steatorrhea, which were similar to those associated with ACP. The prevalence of CP-related gene variants in LMA-CP was 38.3%, similar to ACP (39.8%), although significantly lower than ICP (56.2%). Alcohol consumption enhanced the risk of a poor clinical outcome, whereas genetic factors amplified alcohol's effects. Compared with ICP, LMA-CP and ACP were associated with a high risk of pancreatic stones (patients without variants, OR = 2.01 and 2.54; patients with variants, OR = 2.17 and 1.07), pseudocyst (patients without variants, OR = 1.03 and 1.43; patients with variants, OR = 1.67 and 2.14), diabetes mellitus (patients without variants, OR = 0.86 and 1.31; patients with variants, OR = 2.05 and 1.55), and steatorrhea (patients without variants, OR = 1.56 and 2.10; patients with variants, OR = 2.11 and 1.60).

Evidence was presented to show that LMA-CP was clinically and genetically similar to ACP but significantly different from ICP. Our findings provide support to the growing view that there is no safe level of alcohol consumption.

Mutation-induced protein misfolding of pancreatic secretory enzymes and consequent endoplasmic reticulum stress can cause chronic pancreatitis. A recent study revealed that cigarette smoke also increases the risk of the disease through endoplasmic reticulum stress. Here, we investigated the cumulative cellular effect of the G233E misfolding human pancreatic lipase variant and hydroquinone; a main toxic constituent of cigarette smoke, using mammalian cell lines. We found that hydroquinone reduces cell viability on a dose-dependent manner through programmed cell death, and diminishes lipase secretion without affecting its expression. Interestingly, hydroquinone decreased the viability more markedly in cells expressing the G233E lipase variant, than in cells producing wild-type lipase. The more substantial viability loss was due to increased endoplasmic reticulum stress, as demonstrated by elevated levels of X-box binding protein 1 mRNA splicing and immunoglobulin binding protein, NAD(P)H:quinone oxidoreductase 1 and C/EBP homologous protein expression. Unresolved endoplasmic reticulum stress, and especially up-regulation of the pro-apoptotic transcription factor C/EBP homologous protein were likely responsible for the increased cell death. Our observations demonstrated that the combination of hydroquinone and misfolding pancreatic lipase variant promote increased levels of endoplasmic reticulum stress and cell death, which may predispose to chronic pancreatitis.

Objective: Pancreatic adenocarcinoma (PDAC) and mass forming chronic pancreatitis (CP) can be easily misdiagnosed due to their resemblances in clinical, radiological, and biochemical criteria. In our previous study, we reported a very high concentration of D-Dimers in portal blood in patients with pancreatic cancer which may help to differentiate malignant from benign pancreatic tumours. In this study, we aim to describe other portal and peripheral coagulation profiles of PDAC in comparison to CP patients, as well to test the hypothesis; thus, it is possible to distinguish pancreatic malignancy and benign tumour based on these parameters. Methods: We included retrospectively 115 patients with the absence of venous thromboembolism (VTE), qualified to surgical treatment due to pancreatic tumours, both PDAC and CP. Patients underwent surgery in General and Transplant Surgery Unit of Medical University of Lodz between December 2011 and February 2014. Patients with distant metastases diagnosed before or during the surgery were excluded. The coagulation profile, which includes fibrinogen, activated partial thromboplastin time (aPTT), prothrombin time (PT), and thrombin time (TT), was determined in blood samples from the portal and peripheral vein taken intraoperatively. Results: The fibrinogen level was higher and the aPTT index shortened in the peripheral and portal blood of the PDAC group, which reflects the well-known link between PDAC and general hypercoagulability. Furthermore, these effects are sex-specific. The mean age in the CP group was lower than in the PDAC group (54.63 ± 12.37 vs. 63.77 ± 3.23, p < 0.001) and correlated with the fibrinogen distribution in male patients with CP (portal r = 0.34; p = 0.07; peripheral r = 0.39; p = 0.04). We calculated sex-specific logistic regression models (male: peripheral aPTT and age, AUC: 0.795, female: portal fibrinogen and age, AUC: 0.805), both maintaining the good discrimination properties after V-fold cross validation (0.759, 0.742). Conclusions: Our study shows that the differences between coagulation profiles in PDAC and CP patients not only seems to be a reflection of gender-specific biological features, but also helps to discriminate between them. The main goal of the study was to explore the biology of pancreatic cancer and lay a solid base for further investigations of PDAC biomarkers. This paper is the first to describe the detailed coagulation profile in portal blood in patients with pancreatic solid tumors. At present, the clinical application of our results is not clear; however, we hope that it may improve our understanding of this complex disease.

Acute recurrent pancreatitis (ARP) due to alcohol and/or tobacco abuse is a preventable disease which lowers quality of life and can lead to chronic pancreatitis. The REAPPEAR study aims to investigate whether a combined patient education and cessation programme for smoking and alcohol prevents ARP.

The REAPPEAR study consists of an international multicentre randomised controlled trial (REAPPEAR-T) testing the efficacy of a cessation programme on alcohol and smoking and a prospective cohort study (REAPPEAR-C) assessing the effects of change in alcohol consumption and smoking (irrespective of intervention). Daily smoker patients hospitalised with alcohol-induced acute pancreatitis (AP) will be enrolled. All patients will receive a standard intervention priorly to encourage alcohol and smoking cessation. Participants will be subjected to laboratory testing, measurement of blood pressure and body mass index and will provide blood, hair and urine samples for later biomarker analysis. Addiction, motivation to change, socioeconomic status and quality of life will be evaluated with questionnaires. In the trial, patients will be randomised either to the cessation programme with 3-monthly visits or to the control group with annual visits. Participants of the cessation programme will receive a brief intervention at every visit with direct feedback on their alcohol consumption based on laboratory results. The primary endpoint will be the composite of 2-year all-cause recurrence rate of AP and/or 2-year all-cause mortality. The cost-effectiveness of the cessation programme will be evaluated. An estimated 182 participants will be enrolled per group to the REAPPEAR-T with further enrolment to the cohort.

The study was approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (40394-10/2020/EÜIG), all local ethical approvals are in place. Results will be disseminated at conferences and in peer-reviewed journals.

NCT04647097.

Chronic pancreatitis (CP) is defined according to the recently proposed mechanistic definition as a pathological fibro-inflammatory syndrome of the pancreas in individuals with genetic, environmental, and/or other risk factors who develop persistent pathological responses to parenchymal injury or stress.

The clinical practice guidelines for CP in Japan were revised in 2021 based on the 2019 Japanese clinical diagnostic criteria for CP, which incorporate the concept of a pathogenic fibro-inflammatory syndrome in the pancreas. In this third edition, clinical questions are reclassified into clinical questions, background questions, and future research questions.

Based on analysis of newly accumulated evidence, the strength of evidence and recommendations for each clinical question is described in terms of treatment selection, lifestyle guidance, pain control, treatment of exocrine and endocrine insufficiency, and treatment of complications. A flowchart outlining indications, treatment selection, and policies for cases in which treatment is ineffective is provided. For pain control, pharmacological treatment and the indications and timing for endoscopic and surgical treatment have been updated in the revised edition.

These updated guidelines provide clinicians with useful information to assist in the diagnosis and treatment of CP.

Smoking has been considered as a risk factor of chronic pancreatitis (CP), but the potential mechanism is still unknown. The major pathological feature of CP is pancreatic fibrosis, whose major functional cells are pancreatic stellate cells (PSCs). Nicotine is the major component of cigarette smoke, our recent study suggested that nicotine has the potential to facilitate pancreatic fibrosis in CP. This study was aimed to analyze the function and mechanism of nicotine on PSCs and pancreatic fibrosis in rats.

In vivo, a rat CP model was induced by intraperitoneal injection of 20 % L-arginine hydrochloride (200 mg/100 g) at 1 h intervals twice per week, nicotine was injected subcutaneously at a dose of 1 mg/kg body weight per day. After four weeks, the pancreatic tissue was collected for H&E, Masson and immunohistochemical staining. In vitro, primary rPSCs were isolated from rats and treated with nicotine (0.1 μM and 1 μM). The proliferation、apoptosis、α-SMA expression、extracellular matrix (ECM) metabolism and α7nAChR-mediated JAK2/STAT3 signaling pathway of rPSCs were detected by CCK-8 assay、flow cytometry、real-time Q-PCR and western blotting analysis. The α7nAChR antagonist α-bungarotoxin (α-BTX) was used to perform inhibition experiments.

Nicotine increased pancreatic damage, collagen deposition and activation of PSCs in the CP rat model. In rPSCs, the proliferation, α-SMA expression and ECM formation were significantly promoted by nicotine in a dose-dependent manner. Meanwhile, the apoptosis of rPSCs was significantly reduced after nicotine treatment. Moreover, nicotine also activated the α7nAChR-mediated JAK2/STAT3 signaling pathway in rPSCs. These effects of nicotine on rPSCs were blocked by α-BTX.

Our finding in this research suggests that nicotine facilitates pancreatic fibrosis by promoting activation of pancreatic stellate cells via α7nAChR-mediated JAK2/STAT3 signaling pathway in rats, partly revealing the mechanism of smoking on chronic pancreatitis.

There is a paucity of information on the epidemiology of acute pancreatitis (AP) in Australia.

Data on hospital admissions for a principal diagnosis of AP were obtained from the Australian Institute of Health and Welfare; population data were extracted from the Australian Bureau of Statistics. Age-adjusted, and age and sex-specific rates for all subtypes of AP were compared.

There were 208  390 admissions for a principal diagnosis of AP in Australia between 2006/07 and 2018/19, corresponding to an average admission rate of 46.03/10⁵ /year. Over the study, there was a 38.7% increase in the age-adjusted rate of AP admissions [37.56 to 52.09/10⁵ /year (P < 0.00001)], corresponding to an average increase of 3.0%/year. Unspecified AP comprised approximately 50% of admissions in each year. An increase in admission rates was observed for all categories of AP. Biliary AP admission rates increased from 8.28 to 13.90 /10⁵ /year (P < 0.00001), increasing in both sexes and all age groups. Alcohol associated AP admissions increased from 8.23 to 9.98/10⁵ /year (P < 0.00001), a phenomenon which was seen in older people and in females particularly, but there was a reduction alcohol related AP admission rates in the 20-29-year age group.

AP admission rates increased significantly over the period 2006/07 to 2018/19 in both male and female populations, in most subtypes of AP, particularly 'unspecified AP', and among all age groups.

Postpancreatitis diabetes mellitus (PPDM) is a type of secondary diabetes that requires special considerations for management. The main objective was to examine prescription patterns of glucose-lowering therapy among adults with PPDM compared with type 1 and type 2 diabetes.

In a Danish nationwide population-based cohort study, we identified all individuals with adult-onset diabetes in the period 2000-2018 and categorized them as having type 1 diabetes, type 2 diabetes, or PPDM. We ascertained diabetes incidence rates, clinical and demographic characteristics, and classifications and prescription patterns of glucose-lowering therapy and compared these parameters across diabetes subgroups.

Among 398,456 adults with new-onset diabetes, 5,879 (1.5%) had PPDM, 9,252 (2.3%) type 1 diabetes, and the remaining type 2 diabetes (96.2%). The incidence rate of PPDM was 7.9 (95% CI 7.7-8.1) per 100,000 person-years versus 12.5 (95% CI 12.2-12.7) for type 1 diabetes (incidence rate ratio 0.6 [95% CI 0.6-0.7]; P < 0.001). A sizeable proportion of patients with PPDM were classified as having type 2 diabetes (44.9%) and prescribed sulfonylureas (25.2%) and incretin-based therapies (18.0%) that can potentially be harmful in PPDM. In contrast, 35.0% of patients never received biguanides, which are associated with a survival benefit in PPDM. Increased insulin requirements were observed for patients with PPDM compared with type 2 diabetes (hazard ratio 3.10 [95% CI 2.96-3.23]; P < 0.001) in particular for PPDM associated with chronic pancreatitis (hazard ratio 4.30 [95% CI 4.01-4.56]; P < 0.001).

PPDM is a common type of secondary diabetes in adults but is often misclassified and treated as type 2 diabetes, although PPDM requires special considerations for management.

Chronic pancreatitis is a clinical entity that results from the progressive inflammation and irreversible fibrosis of the pancreas resulting from the cumulative injury sustained by the pancreas over time. It is an illness with variable presentations that can severely impact quality of life, while its long-term complications such as exocrine pancreatic insufficiency (EPI), diabetes mellitus, and risk of pancreatic cancer can become life threatening. The diagnosis of chronic pancreatitis can be challenging as despite the recent advancements in imaging technology, the radiographic findings do not become prominent until late stages of disease. Thus, the physicians' clinical acumen in obtaining thorough history taking focusing on risk factors, clinical symptoms, in addition to high-quality imaging, often guide to the accurate diagnosis of chronic pancreatitis. Endoscopy also plays a pivotal role in the diagnosis and management of chronic pancreatitis. Endoscopic ultrasound (EUS) is believed to be the most sensitive modality for diagnosing chronic pancreatitis. Despite efforts, however, natural history studies have demonstrated that 61% of individuals with chronic pancreatitis will require at least one endoscopic intervention, while 31% will require a surgical procedure as part of their management strategy. Recent advancements in genomic studies have furthered our understanding of the genetic polymorphisms that are associated with the pathogenesis of chronic pancreatitis. Genetic testing offers the potential to reveal treatable pancreatitis-related disorders, and can inform decision making with regard to radical therapies for persistent or severe disease such as total pancreatectomy with islet autotransplantation (TPIAT). The management of patients suffering from chronic pancreatitis often requires a multi-disciplinary approach, addressing pertinent symptoms as well as the sequelae of chronic inflammation and fibrosis. Abdominal pain is the prevailing symptom and most common complication of chronic pancreatitis, and impairs quality of life. Although heavily dependent on a wide range of analgesia, endoscopic treatment such as endoscopic retrograde cholangiopancreatography (ERCP) and surgical intervention can offer long-lasting relief of symptoms. For EPI, treatment with pancreatic enzyme supplements offers marginal-to-moderate relief. The most feared complication of chronic pancreatitis-the development of pancreatic cancer-has no known prevention measure to date.

Chronic pancreatitis (CP) should be suspected in the case of recurrent upper abdominal pain of unknown origin and/or clinical signs of exocrine pancreatic insufficiency (EPI). Alcohol is the most common etiological factor associated with CP, others being smoking, male gender, and hereditary forms. CP is often associated with recurrent episodes of acute exacerbations.As of today, there is no accepted clinical definition of CP. However, irreversible morphological changes within the pancreas often occur, including dilatation of the main and branch pancreatic ducts, calcifications in ducts and parenchyma, parenchymal atrophy, and development of pseudocysts, though less so in the early phase of CP.

Updated population-based estimates on incidence and prevalence of chronic pancreatitis are scarce.

We used nationwide healthcare registries to identify all Danish patients diagnosed with chronic pancreatitis and computed crude and standardised incidence rates and prevalence estimates in 1994-2018. Incidence and prevalence were evaluated in relation to patients age and gender, aetiology (alcoholic vs. non-alcoholic) and smoking and alcohol consumption in the general Danish population.

The mean incidence rate of chronic pancreatitis during the study period was 12.6 per 100,000 person years for the total population, for women it was 8.6 per 100,000 person years and for men it was 16.7 per 100,000 person years. The standardised incidence rate was stable from 1994 to 2018, remaining at 12.5 per 100,000 person years in the last observation period (2014-2018). The point prevalence of chronic pancreatitis in 2016 was 153.9 per 100,000 persons. A gradual increase in standardised prevalence estimates was observed during the study period from 126.6 in 1996 to 153.9 in 2016. The mean age at chronic pancreatitis diagnosis increased from 52.1 to 60.0 years during the study period.

The prevalence of chronic pancreatitis is increasing in the Danish population despite a stable incidence level. Improved management strategies and changes in the underlying patient population may explain these observations.

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.

We conducted this study to ascertain whether chronic inflammation secondary to chronic pancreatitis (CP) has any association with myocardial infarction(MI).

Data were collected from a commercial database (Explorys, Inc, IBM Watson, Ohio). Adults with the diagnosis of "chronic pancreatitis," based on Systematized Nomenclature of Medicine-Clinical Terms, were included in the CP group, and the rest of the patients were included in the non-CP group. The prevalence of MI was compared in both groups, and statistical multivariate model was performed.

A total of 28,842,210 patients were included in the study. The overall prevalence of MI was 14.22% in the CP group as compared with 3.23% in the non-CP group (P < 0.0001). In the multivariate analysis, the odds ratio (OR) for MI in CP group was 1.453 (95% confidence interval, 1.418-1.488, P < 0.0001). Hypertension was a strong predictor for MI in the CP group with an OR of 3.2 (95% confidence interval, 3.0-3.5), followed by chronic kidney disease, older than 65 years, dyslipidemia, diabetes mellitus, obesity, alcohol abuse, smoking, White race, and male sex.

This study showed that CP is associated with comorbidities, which can increase the prevalence and OR of MI.

Chronic pancreatitis (CP) is a complex inflammatory disease with remarkably impaired quality of life and permanent damage of the pancreas. This paper is part of the international consensus guidelines on CP and presents the consensus on factors elevating the risk for CP.

An international working group with 20 experts on CP from the major pancreas societies (IAP, APA, JPS, and EPC) evaluated 14 statements generated from evidence on four questions deemed to be the most clinically relevant in CP. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the level of evidence available per statement. To determine the level of agreement, the working group voted on the 14 statements for strength of agreement, using a nine-point Likert scale in order to calculate Cronbach's alpha reliability coefficient.

Strong consensus and agreement were obtained for the following statements: Alcohol, smoking, and certain genetic alterations are risk factors for CP. Past history, family history, onset of symptoms, and life-style factors including alcohol intake and smoking history should be determined. Alcohol consumption dose-dependently elevates the risk of CP up to 4-fold. Ever smokers, even smoking less than a pack of cigarettes per day, have an increased risk for CP, as compared to never smokers.

Both genetic and environmental factors can markedly elevate the risk for CP. Therefore, health-promoting lifestyle education and in certain cases genetic counselling should be employed to reduce the incidence of CP.

This feasibility and validation study addresses the potential use of magnetic resonance imaging (MRI) texture analysis of the pancreas in patients with chronic pancreatitis (CP).

Extraction of 851 MRI texture features from diffusion weighted imaging (DWI) of the pancreas was performed in 77 CP patients and 22 healthy controls. Features were reduced to classify patients into subgroups, and a Bayes classifier was trained using a tenfold cross-validation forward selection procedure. The classifier was optimized to obtain the best average m-fold accuracy, sensitivity, specificity, and positive predictive value. Classifiers were: presence of disease (CP vs. healthy controls), etiological risk factors (alcoholic vs. nonalcoholic etiology of CP and tobacco use vs. no tobacco use), and complications to CP (presumed pancreatogenic diabetes vs. no diabetes and pancreatic exocrine insufficiency vs. normal pancreatic function).

The best classification performance was obtained for the disease classifier selecting only five of the original features with 98% accuracy, 97% sensitivity, 100% specificity, and 100% positive predictive value. The risk factor classifiers obtained good performance using 9 (alcohol: 88% accuracy) and 10 features (tobacco: 86% accuracy). The two complication classifiers obtained similar accuracies with only 4 (diabetes: 83% accuracy) and 3 features (exocrine pancreatic function: 82% accuracy).

Pancreatic texture analysis demonstrated to be feasible in patients with CP and discriminate clinically relevant subgroups based on etiological risk factors and complications. In future studies, the method may provide useful information on disease progression (monitoring) and detection of biomarkers characterizing early-stage CP.

Diabetes mellitus is a common complication of chronic pancreatitis. It is traditionally considered to develop as a consequence of beta cell loss, but there might be additional factors. Recent studies have highlighted the importance of type 2 diabetes-related risk factors in this context and population-based studies show increased risk of diabetes following acute pancreatitis. The aim of this study was to explore multiple risk factors for diabetes in patients with chronic pancreatitis.

We conducted a multicentre, cross-sectional study of patients with definitive chronic pancreatitis according to the M-ANNHEIM criteria. We used multivariable logistic regression models to determine risk factors independently associated with diabetes.

The study included 1117 patients of whom 457 (40.9 %) had diabetes. The mean age was 52.8 ± 14.2 years and 67% were men. On multivariate analysis, parameters indicative of beta cell loss (pancreatic calcification, exocrine insufficiency, pancreatic resection) were confirmed as independent risk factors for diabetes (all p ≤ 0.02). In addition, type 2 diabetes-related risk factors (dyslipidaemia and overweight/obesity) were associated with the presence of diabetes (all p ≤ 0.002). Patients with a history of pancreatic fluid collections (indicative of previous attacks of acute pancreatitis) had a marginally increased risk of diabetes (p = 0.07).

In patients with chronic pancreatitis the presence of diabetes is associated with multiple risk factors including type 2 diabetes-related factors. Our observations attest to the understanding of this entity and may have implications for treatment.

It has been suggested that smoking may be associated with microscopic colitis (MC) in some studies; however, there are conflicting results in the current literature with many of these studies having significant limitations. Our study aims to offer a meta-analysis evaluating the association between MC, including both its subtypes, and smoking.

A systemic review was conducted in PUBMED, Embase, PubMed Central, and ScienceDirect databases from inception through December 2019. Effect estimates from the individual studies were extracted and combined using the random effect, generic inverse variance method of DerSimonian and Laird and a pooled odds ratio (OR) was calculated. Forest plots were generated, and publication bias was assessed for using conventional techniques.

Eight observation studies with a total of 1461 patients with MC were included in this study, 383 of whom were active smokers (26.2%). Current smoking was significantly associated with MC (OR 3.58, 95% CI, 2.51-5.11), lymphocytic colitis (LC) (OR 3.64, 95% CI, 2.46-5.38), and collagenous colitis (CC) (OR 4.43, 95% CI, 2.68-7.32). Gender-specific subgroup analysis showed a significant association with smoking was found for CC in men (OR 4.53, 95% CI, 1.59-12.85), CC in women (OR 3.27, 95% CI, 2.35-4.54), LC in women (OR 2.27, 95% CI, 1.27-4.06) and MC in women (OR 2.93, 95% CI, 2.09-4.10). We found no publication bias as assessed by the funnel plots and Egger's regression asymmetry test.

Our meta-analysis found a statistically significant association between smoking and both subtypes of MC.

Chronic pancreatitis (CP) is historically defined as an irreversible inflammatory condition of the pancreas leading to varying degrees of exocrine and endocrine dysfunction. Recently however, the paradigm for the diagnosis has changed in that it breaks with the traditional clinicopathologic-based definition of disease, focusing instead on diagnosing the underlying pathologic process early in the disease course and managing the syndrome more holistically to change the natural course of disease and minimize adverse disease effects. Currently, the most accepted mechanistically derived definition of CP is a pathologic fibroinflammatory syndrome of the pancreas in individuals with genetic, environmental, and/or other risk factors who develop persistent pathologic responses to parenchymal injury or stress. The most common symptom of CP is abdominal pain, with other symptoms such as exocrine pancreatic insufficiency and diabetes developing at highly variable rates. CP is most commonly caused by toxins such as alcohol or tobacco use, genetic polymorphisms, and recurrent attacks of acute pancreatitis, although no history of acute pancreatitis is seen in many patients. Diagnosis is made usually on cross-sectional imaging, with modalities such as endoscopic ultrasonography and pancreatic function tests playing a secondary role. Total pancreatectomy represents the only known cure for CP, although difficulty in patient selection and the complications inherent to this intervention make it usually an unattractive option. This guideline will provide an evidence-based practical approach to the diagnosis and management of CP for the general gastroenterologist.

Pain is the primary symptom of chronic pancreatitis (CP) and associates with a number of patient and disease characteristics. However, the complex interrelations of these parameters are incompletely understood, and pain treatment remains unsatisfactory in a large proportion of patients. The aim of this study is to investigate multiple pain risk factors in a large population of CP patients, with a special emphasis on patients' patterns of smoking and alcohol use.

This was a multicenter, cross-sectional study including 1384 patients with CP. Patient demographics and disease characteristics, as well as current patterns of smoking and alcohol use, were compared for patients with pain (n = 801) versus without pain (n = 583). Multivariate logistic regression models were performed to assess the variables associated with the presence and type of pain (constant vs intermittent pain).

The mean age of participants was 52.1 ± 14.6 years, and 914 (66%) were men. Active smoking (odds ratio 1.6 [95% confidence interval 1.1-2.2], P = 0.005) and alcohol consumption (odds ratio 1.8 [95% confidence interval 1.1-3.0], P = 0.03) were independently associated with the presence of pain. In addition, patients' age at diagnosis, pancreatic duct pathology, and the presence of pseudocysts, duodenal stenosis, and exocrine pancreatic insufficiency were confirmed as pain risk factors (all P ≤ 0.01). Constant pain, as opposed to intermittent pain, was more frequently reported by smokers (P = 0.03), while alcohol consumption was associated with intermittent pain (P = 0.006).

Multiple patient and disease characteristics, including patterns of smoking and alcohol consumption, associate with the presence and type of pain in patients with CP.

Chronic pancreatitis (CP) is a chronic inflammatory and fibrotic disease of the pancreas with a prevalence of 42 to 73 per 100 000 adults in the United States.

Both genetic and environmental factors are thought to contribute to the pathogenesis of CP. Environmental factors associated with CP include alcohol abuse (odds ratio [OR], 3.1; 95% CI, 1.87-5.14) for 5 or more drinks per day vs abstainers and light drinkers as well as smoking (OR, 4.59; 95% CI, 2.91-7.25) for more than 35 pack-years in a case-control study involving 971 participants. Between 28% to 80% of patients are classified as having "idiopathic CP." Up to 50% of these individuals have mutations of the trypsin inhibitor gene (SPINK1) or the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Approximately 1% of people diagnosed with CP may have hereditary pancreatitis, associated with cationic trypsinogen (PRSS1) gene mutations. Approximately 80% of people with CP present with recurrent or chronic upper abdominal pain. Long-term sequelae include diabetes in 38% to 40% and exocrine insufficiency in 30% to 48%. The diagnosis is based on pancreatic calcifications, ductal dilatation, and atrophy visualized by imaging with computed tomography, magnetic resonance imaging, or both. Endoscopic ultrasound can assist in making the diagnosis in patients with a high index of suspicion such as recurrent episodes of acute pancreatitis when imaging is normal or equivocal. The first line of therapy consists of advice to discontinue use of alcohol and smoking and taking analgesic agents (nonsteroidal anti-inflammatory drugs and weak opioids such as tramadol). A trial of pancreatic enzymes and antioxidants (a combination of multivitamins, selenium, and methionine) can control symptoms in up to 50% of patients. Patients with pancreatic ductal obstruction due to stones, stricture, or both may benefit from ductal drainage via endoscopic retrograde cholangiopancreatography (ERCP) or surgical drainage procedures, such as pancreaticojejunostomy with or without pancreatic head resection, which may provide better pain relief among people who do not respond to endoscopic therapy.

Chronic pancreatitis often results in chronic abdominal pain and is most commonly caused by excessive alcohol use, smoking, or genetic mutations. Treatment consists primarily of alcohol and smoking cessation, pain control, replacement of pancreatic insufficiency, or mechanical drainage of obstructed pancreatic ducts for some patients.

Tobacco smoking has been associated with increased risk of pancreatitis in several studies, however, not all studies have found an association and it is unclear whether there is a dose-response relationship between increasing amount of tobacco smoked and pancreatitis risk. We conducted a systematic review and meta-analysis of prospective studies on tobacco smoking and pancreatitis to clarify the association.

PubMed and Embase databases were searched for relevant studies up to April 13th^, 2019. Prospective studies that reported adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) for the association between tobacco smoking and pancreatitis were included and summary RRs were calculated using a random effects model.

Ten prospective studies were included. The summary RR for acute pancreatitis was 1.49 (95% CI: 1.29-1.72, I² = 68%, n = 7) for current smokers, 1.24 (95% CI: 1.15-1.34, I² = 0%, n = 7) for former smokers, and 1.39 (95% CI: 1.25-1.54, I² = 69%, n = 7) for ever smokers compared to never smokers. Similar results were observed for chronic pancreatitis and acute/chronic pancreatitis combined. The summary RR per 10 cigarettes per day was 1.30 (95% CI: 1.18-1.42, I² = 42%, n = 3) and per 10 pack-years in current smokers was 1.13 (95% CI: 1.08-1.17, I² = 14%, n = 4) for acute pancreatitis and results were similar for chronic pancreatitis and acute/chronic pancreatitis combined.

These results suggest that tobacco smoking increases the risk of acute and chronic pancreatitis and acute and chronic pancreatitis combined and that there is a dose-response relationship between increasing number of cigarettes and pack-years and pancreatitis risk.

Pancreatic calcifications is a common finding in patients with chronic pancreatitis (CP), but the underlying pathophysiology is incompletely understood. Past studies for risk factors of calcifications have generally been focused on single parameters or limited by small sample sizes. The aim of this study was to explore several patient and disease characteristics and their associations with pancreatic calcifications in a large cohort of CP patients with diverse aetiological risk factors.

This was a multicentre, cross-sectional study including 1509 patients with CP. Patient and disease characteristics were compared for patients with calcifications (n = 912) vs. without calcifications (n = 597). Multivariable logistic regression was performed to assess the parameters independently associated with calcifications.

The mean age of patients was 53.9 ± 14.5 years and 1006 (67%) were men. The prevalence of calcifications was 60.4% in the overall patient cohort, but highly variable between patients with different aetiological risk factors (range: 2-69%). On multivariate analysis, alcoholic aetiology (OR 1.76 [95% CI, 1.39-2.24]; p < 0.001) and smoking aetiology (OR 1.77 [95% CI, 1.39-2.26], p < 0.001) were positively associated with the presence of calcifications, while an autoimmune aetiology was negatively associated with calcifications (OR 0.15 [95% CI, 0.08-0.27], p < 0.001). Patients with pancreatic calcifications were more likely to have undergone pancreatic duct stenting (OR 1.59 [95%CI, 1.16-2.19], p = 0.004).

The presence of pancreatic calcifications is associated with diverse aetiological risk factors in patients with CP. This observation attest to the understanding of CP as a complex disease and may have implications for disease classification.