Naldemedine for the Prevention of Recurrent Acute Pancreatitis: A Randomised, Double‐Blind, Placebo‐Controlled Trial

Purpose: Cigarette smoking is a well-known independent risk factor for pancreatic cancer and chronic pancreatitis. Some recent studies have suggested a causative link with acute pancreatitis, as well. We conducted a systematic review of the literature to assess if (1) cigarette smoking is a risk factor for acute pancreatitis and (2) cigarette smoking is a risk factor for recurrent acute pancreatitis. Methods: We searched MEDLINE®, PubMed®, Embase®, and Cochrane Database of Systematic Reviews for studies published from database inception through March 2013. To be eligible for this review, studies had to meet all the following criteria: English-language, peer-reviewed studies with 20 or more human participants; reports quantitative association between exposure to cigarette smoking and acute pancreatitis or recurrent acute pancreatitis and includes comparison group with no tobacco use. Only pooled patient-level meta-analysis or controlled study (e.g. case control) were included. Two investigators independently reviewed articles for eligibility and discordant decisions were resolved by a third investigator's review and consensus.When possible, random-effects metaanalyses were performed by estimating pooled odds ratios (OR) with 95% confidence intervals (CI). We synthesized other studies qualitatively. Results: A total of 1,314 citations were reviewed of which 10 studies were eligible for data abstraction; seven relevant for acute pancreatitis and three for recurrent acute pancreatitis. A meta-analysis of case-control and cohort studies showed acute pancreatitis incidence was slightly but significantly increased in ‘current smokers' compared with ‘never smokers' (five studies; OR 1.95; 95% CI 1.37-2.78) and ‘former smokers' compared to ‘never smokers' (5 studies; OR 1.54; 95% CI=1.07-2.21). The comparison of ‘ever smokers' compared to ‘never smokers' demonstrated a similar association but did not reach significance (five studies; OR 1.36; 95% CI 0.92-2.00). Of the studies that examined the development of recurrent acute pancreatitis, there was a range of effects of smoking (three studies, range OR 1.24-6.80) for ‘ever smokers' compared to ‘never smokers'. Conclusion: This systematic review provides supportive evidence for the association of cigarette smoking and acute pancreatitis. This effect is most pronounced for ‘current smokers' but the risk exists even among the ‘former smokers' compared to ‘never smokers'. There was a trend noted for ‘ever smokers' to have an increased risk of recurrent acute pancreatitis. Future studies should examine the impact of smoking cessation on the risk of acute pancreatitis.

Covering the Cover

This is an overview of relation between acute and chronic pancreatitis and between acute pancreatitis and pancreatic cancer. Acute pancreatitis and recurrent acute pancreatitis are an etiological factor of chronic pancreatitis. Population-based studies have calculated the risk of acute recurrent pancreatitis after the first attack of acute pancreatitis to be 20% and development of chronic pancreatitis after first attack of acute pancreatitis is 10%. An important risk factor is tobacco smoking. Acute and chronic pancreatitis are risk factors for pancreatic cancer. The risk of acute pancreatitis is related to the number of recurrences of acute pancreatitis, but not the etiology of acute pancreatitis. Acute pancreatitis, as well as chronic pancreatitis, are risk factors for pancreatic cancer. After an attack of acute pancreatitis or recurrent acute pancreatitis a patient should be regarded as a high risk.

Data on the incidence and clinical relevance of gallstones in patients with suspected acute alcoholic pancreatitis are lacking and are essential to minimize the risk of recurrent acute pancreatitis. The aim of this study was to assess the incidence of gallstones and the associated rate of recurrent acute pancreatitis in patients with presumed acute alcoholic pancreatitis. Between 2008 and 2019, 23 hospitals prospectively enrolled patients with acute pancreatitis. Those diagnosed with their first episode of presumed acute alcoholic pancreatitis were included in this study. The term gallstones was used to describe the presence of cholelithiasis or biliary sludge found during imaging. The primary outcome was pancreatitis recurrence during 3 years of follow-up. A total of 334 patients were eligible for inclusion, of whom 316 were included in the follow-up analysis. Gallstone evaluation, either during the index admission or during follow-up, was performed for 306 of 334 patients (91.6%). Gallstones were detected in 54 patients (17.6%), with a median time to detection of 6 (interquartile range 0-42) weeks. During follow-up, recurrent acute pancreatitis occurred in 121 of 316 patients (38.3%), with a significantly higher incidence rate for patients with gallstones compared with patients without gallstones (59% versus 34.2% respectively; P < 0.001), while more patients with gallstones had stopped drinking alcohol at the time of their first recurrence (41% versus 24% respectively; P = 0.020). Cholecystectomy was performed for 19 patients with gallstones (36%). The recurrence rate was lower for patients in the cholecystectomy group compared with patients who did receive inadequate treatment or no treatment (5/19 versus 19/34 respectively; P = 0.038). Gallstones were found in almost one in every five patients diagnosed with acute alcoholic pancreatitis. Gallstones were associated with a higher rate of recurrent pancreatitis, while undergoing cholecystectomy was associated with a reduction in this rate.

Genetically Defined Models of Chronic Pancreatitis

The purpose of this study was to investigate the influencing factors for recurrent acute pancreatitis and construct the nomogram model to predict the risk of recurrent acute pancreatitis. Patients diagnosed with acute pancreatitis in the Affiliated Hospital of Southwest Medical University were enrolled. We collected these patients' basic information, laboratory data, imaging information. Using Logistic regression and least absolute shrinkage and selection operator regression to select risk factor for Cross-Validation Criterion. To create nomogram and validated by receiver operator characteristic curve, calibration curves and decision curve analysis. A total of 533 patients with acute pancreatitis were included, including 99 recurrent acute pancreatitis patients. The average age of recurrent acute pancreatitis patients was 49.69 years old, and 67.7% of them were male. At the same time, in all recurrent acute pancreatitis patients, hypertriglyceridemic pancreatitis is the most important reason (54.5%). Regression analysis and least absolute shrinkage and selection operator regression showed that smoking history, acute necrotic collection, triglyceride, and alcohol etiology for acute pancreatitis were identified and entered into the nomogram. The area under the receiver operator characteristic curve of the training set was 0.747. The calibration curve showed the consistency between the nomogram model and the actual probability. In conclusion, some high-risk factors like smoking history, acute necrotic collection, triglyceride, and alcohol etiology for acute pancreatitis may predict recurrent pancreatitis and their incorporation into a nomogram has high accuracy in predicting recurrence.

Cholecystectomy Reduces Recurrent Pancreatitis and Improves Survival After Endoscopic Sphincterotomy

Similar Efficacies of Biliary, With or Without Pancreatic, Sphincterotomy in Treatment of Idiopathic Recurrent Acute Pancreatitis

Cystic fibrosis transmembrane conductance regulator modulators reduce the risk of recurrent acute pancreatitis among adult patients with pancreas sufficient cystic fibrosis

The aim of the study was to understand the association of frequent opioid use with disease phenotype and pain pattern and burden in children and adolescents with acute recurrent (ARP) or chronic pancreatitis (CP). Cross-sectional study of children <19 years with ARP or CP, at enrollment into the INSPPIRE cohort. We categorized patients as opioid "frequent use" (daily/weekly) or "nonfrequent use" (monthly or less, or no opioids), based on patient and parent self-report. Of 427 children with ARP or CP, 17% reported frequent opioid use. More children with CP (65%) reported frequent opioid use than with ARP (41%, P = 0.0002). In multivariate analysis, frequent opioid use was associated with older age at diagnosis (odds ratio [OR] 1.67 per 5 years, 95% confidence interval [CI] 1.13-2.47, P = 0.01), exocrine insufficiency (OR 2.44, 95% CI 1.13-5.24, P = 0.02), constant/severe pain (OR 4.14, 95% CI 2.06-8.34, P < 0.0001), and higher average pain impact score across all 6 functional domains (OR 1.62 per 1-point increase, 95% CI 1.28-2.06, P < 0.0001). Children with frequent opioid use also reported more missed school days, hospitalizations, and emergency room visits in the past year than children with no frequent use (P < 0.0002 for each). Participants in the US West and Midwest accounted for 83% of frequent opioid users but only 56% of the total cohort. In children with CP or ARP, frequent opioid use is associated with constant pain, more healthcare use, and higher levels of pain interference with functioning. Longitudinal and prospective research is needed to identify risk factors for frequent opioid use and to evaluate nonopioid interventions for reducing pain and disability in these children.

Several gastrointestinal diseases have been linked to acute pancreatitis, but the risk of acute pancreatitis in microscopic colitis (MC) has not been studied. We conducted a nationwide, population-based, matched cohort study in Sweden of 12,140 patients with biopsy-verified MC (diagnosed in 2003-2017), 57,806 matched reference individuals, and 12,781 siblings without MC with a follow-up until 2021. Data on MC were obtained from all of Sweden's regional pathology registers (n = 28) through the ESPRESSO cohort. Data on acute pancreatitis were collected from the National Patient Register. Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) were calculated using Cox regression. During a mean follow-up of 9.9 years (SD = 4.3), 146 patients with MC and 437 reference individuals were diagnosed with acute pancreatitis (127.8 vs 80.1 per 100,000 person-years), corresponding to an aHR of 1.57 (95% CI = 1.30-1.90). Moreover, we found a positive association between MC and acute nongallstone-related pancreatitis (aHR 1.99 [95% CI = 1.57-2.51]), but not with acute gallstone-related pancreatitis (aHR 1.08 [95% CI = 0.78-1.49]). Comparing patients with MC with their unaffected siblings yielded an aHR of 1.28 (95% CI = 0.92-1.78). The risk of acute pancreatitis remained elevated also for patients with MC with a follow-up exceeding 10 years (aHR 1.75 [95% CI = 1.14-2.67]). This nationwide study of more than 12,000 patients with MC demonstrated an increased risk of acute pancreatitis after MC. Hence, clinicians should have a low threshold for the evaluation of acute pancreatitis in patients with MC. In addition, these patients should receive advice and care aimed at reducing the risk of acute pancreatitis.

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We prospectively assessed the age- and sex-specific incidence rates and relative risks of overall and severe acute pancreatitis in Taiwanese with diabetes. The study cohort included age- and-sex-matched groups of patients with (n = 547,554) and without (n = 584,373) diabetes. Incidence rate was estimated under Poisson assumption and relative risks of acute pancreatitis and severe acute pancreatitis, based on modified Atlanta criteria, were indicated by hazard ratios estimated from Cox proportional hazard regression models. Over an 8-year follow-up period, the incidence of acute pancreatitis was 2.98 and 1.68 per 1000 person-years for patients with and without diabetes, respectively, representing a covariate adjusted hazard ratio of 1.53 (95% confidence interval 1.49-1.58). Diabetes was associated with a significantly elevated risk of acute pancreatitis in all sex and age stratifications, with the highest hazard ratio noted for study subjects aged < 45 years (men 2.37; women 2.95). Diabetes was also significantly associated with an increased hazard ratio of severe acute pancreatitis [1.46 (1.36-1.57)], and especially of acute pancreatitis with local complications [1.65 (1.14-2.39)]. Diabetes is associated with an increased risk of overall and severe acute pancreatitis, and the relation is stronger in women and young patients.

Alcohol Consumption in Patients with Acute or Chronic Pancreatitis

A Patient With Pancreas Divisum, Recurrent Acute Pancreatitis, and Homozygosity for the Cystic Fibrosis Transmembrane Regulator–Associated Protein 5T Allele