No Effect of Methylnaltrexone on Acute Pancreatitis Severity: A Multicenter Randomized Controlled Trial.

OBJECTIVES: Opioids used to manage severe pain in acute pancreatitis might exacerbate the disease through effects on gastrointestinal and immune functions. Methylnaltrexone, a peripherally acting µ-opioid receptor antagonist, may counteract these effects without changing analgesia. METHODS: This double-blind, randomized, placebo-controlled trial included adult patients with acute pancreatitis and systemic inflammatory response syndrome at four Danish centers. Participants were randomized to receive five days of continuous intravenous methylnaltrexone (0.15mg/kg/day) or placebo added to the standard of care. The primary endpoint was the Pancreatitis Activity Scoring System score after 48 hours of treatment. Main secondary outcomes included pain scores, opioid use, disease severity, and mortality. RESULTS: In total, 105 patients (54% males) were randomized to methylnaltrexone (n=51) or placebo (n=54). After 48 hours, the Pancreatitis Activity Scoring System score was 134.3 points in the methylnaltrexone group and 130.5 points in the placebo group (difference, 3.8 [95% CI, -40.1 to 47.6]; P=0.87). At 48 hours, we found no differences between groups in pain severity (0.0 [95% CI, -0.8 to 0.9]; P=0.94), pain interference (-0.3 [95% CI, -1.4 to 0.8]; P=0.55), and morphine equivalent doses (6.5 mg [95% CI, -2.1 to 15.2]; P=0.14). Methylnaltrexone also did not affect the risk of severe disease (8% [95% CI, -11 to 28]; P=0.38) and mortality (6% [95% CI, -1 to 12]; P=0.11). The medication was well-tolerated. CONCLUSIONS: Methylnaltrexone treatment did not achieve superiority over placebo for reducing the severity of acute pancreatitis.

Novel powered 5.0-mm endoscopic debridement catheter for endoscopic transmural necrosectomy of pancreatic walled-off necrosis: a case series of consecutive patients from a tertiary referral center (with video).

BACKGROUND AND AIMS: EUS-guided drainage and, if required, endoscopic necrosectomy (EN) has become the criterion standard for the treatment of pancreatic walled-off necrosis (WON). A dedicated powered endoscopic debridement system, the EndoRotor (Interscope Inc, Northbridge, Mass, USA), has been introduced as an alternative to snare necrosectomy. This study evaluates the novel EndoRotor catheter, NecroMax 6.0 (Interscope Inc, Whitinsville, Mass, USA), for EN in patients with WON. METHODS: This single-center retrospective case series included consecutive patients with WON treated with the NecroMax 6.0 catheter. Safety, ability to perform EN, and clinical resolution were evaluated. RESULTS: Twenty patients underwent 30 EN procedures with the NecroMax 6.0 catheter. One suspected device-related adverse event was observed (3.3%). In 1 procedure, EN could not be performed because of excessive bending of the endoscope. Eighteen patients (90.0%) achieved clinical resolution. CONCLUSIONS: EN with the NecroMax 6.0 catheter was technically feasible in 96.7% of patients with a low rate of adverse events.

EUS-guided drainage of large walled-off pancreatic necroses using plastic versus lumen-apposing metal stents: a single-centre randomised controlled trial.

OBJECTIVE: In treating pancreatic walled-off necrosis (WON), lumen-apposing metal stents (LAMS) have not proven superior to the traditional double pigtail technique (DPT). Among patients with large WON (>15 cm) and their associated substantial risk of treatment failure, the increased drainage capacity of a novel 20-mm LAMS might improve clinical outcomes. Hence, we conducted a study comparing the DPT and 20-mm LAMS in patients with large WON. DESIGN: A single-centre, open-label, randomised, controlled superiority trial using an endoscopic step-up approach in patients with WON exceeding 15 cm in size. The primary endpoint was the number of necrosectomies needed to achieve clinical success (clinical and CT resolution), while the secondary endpoints included technical success, adverse events, length of stay and mortality. RESULTS: Twenty-two patients were included in the DPT group and 20 in the LAMS group, with no significant differences in patient characteristics. The median size of WON was 24.1 cm (P25-P75: 19.6-31.1). The technical success rates were 100% for DPT and 95% for LAMS (p=0.48), while clinical success rates were 95.5% and 94.7%, respectively (p=1.0). The mean number of necrosectomies was 2.2 for DPT and 3.2 for LAMS (p=0.42). Five patients (12%) developed procedure-related serious adverse events (DPT=4, LAMS=1, p=0.35). The median length of stay was 43 (P25-P75: 40-67) and 58 days (P25-P75: 40-86) in the DPT and LAMS groups (p=0.71), respectively, with an overall mortality of 4.8%. CONCLUSIONS: For treating large WON, LAMS are not superior to DPT. The techniques are associated with comparable needs for necrosectomy and hospital stay, and no gross difference in adverse events. TRIAL REGISTRATION NUMBER: NCT04057846.

Alcohol Drinking Patterns and Risk of Developing Acute and Chronic Pancreatitis.

AIM: The aim was to analyze the effects of drinking pattern and type of alcohol on risk of acute and chronic pancreatitis. METHODS: Prospective cohort study based on data from 316,751 men and women participating in the Danish National Health Surveys 2010 and 2013. Self-reported questionnaire-based alcohol parameters and information on pancreatitis was obtained from national health registers. Cox regression models were used adjusting for baseline year, gender, age, smoking, Body Mass Index, diet and education. RESULTS: Development of acute and chronic pancreatitis increased with alcohol intake with a significant increase among abstainers and those drinking >14 drinks per week compared with individuals drinking 1-7 drinks per week. Frequent binge drinking and frequent drinking (every day) was associated with increased development of acute and chronic pancreatitis compared with those drinking 2-4 days per week. Problematic alcohol use according to the CAGE-C questionnaire was associated with increased development of acute and chronic pancreatitis.Intake of more than 14 drinks of spirits per week was associated with increased development of acute and chronic pancreatitis, and more than 14 drinks of beer per week were associated with increased development of chronic pancreatitis, whereas drinking wine was not associated with development of pancreatitis. CONCLUSION: This large prospective population study showed a J-shaped association between alcohol intake and development of pancreatitis. Drinking every day, frequent binge drinking and problematic alcohol use were associated with increased development of pancreatitis and drinking large amounts of beer and spirits might be more harmful than drinking wine.

Exocrine pancreas insufficiency in chronic pancreatitis - Risk factors and associations with complications. A multicentre study of 1869 patients.

BACKGROUND/OBJECTIVES: There is scarce information about risk factors for exocrine pancreas insufficiency (EPI) in chronic pancreatitis (CP), and how it associates with other complications. The aim of the present study was to examine risk factors for EPI and associations to procedures and other CP related complications in a large, Northern European cohort. PATIENTS AND METHODS: We retrieved cross-sectional data on demographics, status on EPI, aetiological risk factors for CP, CP related complications as well as surgical and endoscopic treatment from the Scandinavian Baltic Pancreatic Club Database. Associations were assessed by univariate and multivariate logistic regression analyses. Results are presented as odds ratios (OR) with 95% confidence intervals. RESULTS: We included 1869 patients with probable or definitive CP in the study. Exocrine pancreas insufficiency was present in 849 (45.4%) of patients. In multivariate analyses, EPI associated with smoking aetiology (OR 1.47 (1.20-1.79), p < 0.001), and nutritional/metabolic aetiology (OR 0.52 (0.31-0.87), p = 0.01) to CP. Pancreatic or common bile duct stenting procedure and pancreatic resection were both associated with EPI (ORs 1.44 (1.15-1.80), p = 0.002 and 1.54 (1.02-2.33), p = 0.04, respectively). The presence of diabetes mellitus (OR 2.45 (1.92-3.15), p < 0.001), bile duct stenosis (OR 1.48 (1.09-2.00), p = 0.02) and underweight (2.05 (OR 1.40-3.02), p < 0.001) were all associated with presence of EPI. CONCLUSIONS: Smoking, bile duct stenosis, previous stenting and resection procedures are all associated with EPI in patients with CP. Presence of EPI were also associated with malnutrition and diabetes mellitus. Hence, intensive nutritional surveillance is needed in these patients.

Long-term changes of pancreatic function in patients with complicated walled-off necrosis.

OBJECTIVES: Walled-off necrosis (WON) is a serious complication to necrotizing acute pancreatitis with a high morbidity and mortality. The aim of this study was to investigate the long-term changes in pancreatic function, metabolic function and body composition in patients with WON. MATERIAL AND METHODS: Observational study including patients with WON who underwent endoscopic transmural drainage and necrosectomy. Patients were prospectively evaluated at baseline, 3-6 months after discharge, and 12 months after discharge. Patients were characterized with fecal elastase, blood samples, computer tomography, dual energy X-ray absorptiometry and Lundh's test. RESULTS: The study includes 17 patients (11 men) with WON. The etiologies were gallstones (53%) alcohol intake (35%) and 12% had an unknown etiology. The body mass index (BMI) dropped during baseline and 3 months after discharge (p = .03) and increased 12 months after discharge (p = .002). Twelve months after discharge, 29% had mild exocrine insufficiency, 7% moderate insufficiency and 50% severe insufficiency based on the Lundh's test. Fecal elastase was <100 µg/g in 35% and <200 µg/g in 59% 12 months after discharge. Only, 24% required pancreatic enzyme substitution. Endocrine insufficiency developed in 24%. These patients also had exocrine insufficiency. CONCLUSIONS: A considerable proportion of patients with WON experience both endocrine and exocrine pancreatic insufficiency suggesting that long-term follow-up is needed in order to ensure adequate treatment.

Confusion with the definition and diagnostic criteria for acute on chronic pancreatitis: review and recommendations.

OBJECTIVES: Chronic pancreatitis (CP) is a fibroinflammatory disease complicated by episodes of acute inflammation (acute on chronic pancreatitis (ACP)). This entity is common, variably defined and can reflect different pathological mechanisms that requires different interventions. The aim of this study is to conduct a systematic review of how ACP is described, defined and diagnosed in the literature. METHODS: A systematic search was conducted from January 1993 to June 2020. All articles that used a term to describe ACP in adults were reviewed and definitions and diagnostic criteria were sought. RESULTS: After reviewing 2271 abstracts, 848 articles included a term to describe ACP. The most common descriptions were 'acute on/in CP' (374), 'acute exacerbation of CP' (345) and 'flare(-up) of CP' (43). Among the 848 articles, 14 included a pragmatic definition of ACP, and only 2 papers stated diagnostic criteria. These covered both acute inflammation and acute exacerbation of chronic abdominal pain. CONCLUSION: There is no universally accepted term, definition or diagnostic criteria for ACP. A consensus definition is needed to improve quality and comparability of future articles as well as clinical management.

Clinical outcomes following endoscopic or video-assisted retroperitoneal management of acute pancreatitis with large (>15 cm) walled-off pancreatic necrosis: Retrospective, single tertiary center cohort study.

OBJECTIVE: Acute pancreatitis with walled-off necrosis (WON) is associated with considerable morbidity and mortality. Previous studies have evaluated outcomes in WON collections of limited size, while data about large WON with long-term follow-up are lacking. We aimed to report our experience in managing large WON. METHODS: Between 2010 and 2020, consecutive patients with large (>15 cm) WON were identified from a prospectively maintained database. Patients with chronic pancreatitis or an index intervention 90 days or more from the debut of symptoms were excluded. We registered clinical and technical outcomes following minimally invasive treatment in WON >15 cm. Follow-up was a minimum of 1 year. RESULTS: Overall, 144 patients with WON >15 cm, with a median age of 60 (interquartile range [IQR] 49-69) years, were included. The median WON size was 19.2 cm (IQR 16.8-22.1). Most patients were treated with endoscopic transluminal drainage (93%). The median length of stay was 53 days (IQR 39-76) and 61 (42%) patients needed intensive care support during their hospital stay. As 143 patients (99%) were managed using endoscopic or video-assisted retroperitoneal techniques, only one (0.7%) patient needed an open necrosectomy. Procedure-related adverse events occurred in 10 (7%) patients. Overall, 24 patients (17%) died during admission, all due to multiorgan failure. The median follow-up was 35 months (IQR 15-63.5). Complete resolution was achieved in all remaining patients. CONCLUSION: Minimally invasive treatment of large WON is feasible, with a minimal need for surgery and acceptable rates of morbidity and mortality.

Aetiological risk factors are associated with distinct imaging findings in patients with chronic pancreatitis: A study of 959 cases from the Scandinavian Baltic Pancreatic Club (SBPC) imaging database.

OBJECTIVES: The relation between aetiology and structural changes of the pancreas in patients with chronic pancreatitis (CP) is not fully understood. Earlier studies are limited by focusing on selected factors in studies of limited sample size. We aimed to use a large dataset to explore associations between aetiology and pancreatic morphology in CP. METHODS: Subjects with definite or probable CP according to the M-ANNHEIM diagnostic criteria were included in this multicentre cross-sectional observational study and assessed using a standardized and validated CP imaging system. We performed multivariate logistic regression to analyse if aetiological factors adjusted for covariates were independently associated with morphological pancreatic features. RESULTS: We included 959 patients (66% males). Mean (SD) age was 55 (14) years. Pancreatic structural changes were found in 94% of the subjects: 67% had calcifications, 59% main pancreatic duct dilatation, 33% pseudo-cysts and 22% pancreatic atrophy. Alcohol abuse was independently associated with pancreatic calcifications (odds ratio (OR, [95% CI]); 1.61, [1.09, 2.37]) and focal acute pancreatitis (OR; 2.13, [1.27, 3.56]), whereas smoking was independently associated with more severe calcifications (OR; 2.09, [1.34, 3.27]) and involvement of the whole gland (OR; 2.29, [1.61, 3.28]). Disease duration was positively associated with calcifications (OR; (per year) 1.05 [1.02, 1.08]) and pancreatic atrophy (OR; 1.05 [1.02, 1.08]) and negatively associated with focal acute pancreatitis (OR 0.91, [0.87, 0.95] and pseudo cysts (OR; 0.96, [0.93, 0.98]). CONCLUSION: In this large-scale study, etiological risk factors and disease duration in CP were independently associated with specific structural pancreatic imaging changes.

Coronavirus Disease-19 (COVID-19) associated with severe acute pancreatitis: Case report on three family members.

BACKGROUND/OBJECTIVES: Abdominal pain is one of the known symptoms associated with coronavirus disease 2019. Little is known about the development of acute pancreatitis as a complication of severe acute respiratory syndrome coronavirus 2 infection. This case report describes the presentation of acute pancreatitis in two of three family members with severe COVID-19 infection. METHODS: Data were collected from three family members admitted with COVID-19 to the intensive care unit in March 2020. This study was reviewed and approved by the local data and ethics committee (31-1521-253). RESULTS: Two of the three family members were diagnosed with acute pancreatitis associated with SARS-CoV-2. Other causes of acute pancreatitis were excluded for both patients (including alcohol, biliary obstruction/gall stones, drugs, trauma, hypertriglyceridemia, hypercalcemia, and hypotension). CONCLUSIONS: These cases highlight acute pancreatitis as a complication associated with COVID-19 and underlines the importance of measuring pancreas-specific plasma amylase in patients with COVID-19 and abdominal pain.

Pain and aetiological risk factors determine quality of life in patients with chronic pancreatitis, but a brick in the puzzle is missing.

BACKGROUND AND OBJECTIVES: Chronic pancreatitis (CP) is a debilitating fibro-inflammatory disease with a profound impact on patients' quality of life (QOL). We investigated determinants of QOL in a large cohort of CP patients. METHODS: This was a multicentre study including 517 patients with CP. All patients fulfilled the EORTC QLQ-C30 questionnaire. Questionnaire responses were compared to results obtained from a general reference population (n = 11,343). Demographic characteristics, risk factors (smoking and alcohol consumption), pain symptoms, disease phenotype (complications) and treatments were recorded. A multivariable regression model was used to identify factors independently associated with QOL scores. RESULTS: Included patients had a mean age of 56.3 ± 12.8 years, 355 (69%) were men and 309 (60%) had alcohol aetiology. Compared to the reference population, patients with CP had lower global health status (50.5 vs. 66.1; p < 0.001) as well as reduced scores for all functional scales (all p < 0.001). Additionally, CP patients reported a higher burden for all symptom items, with pain being the most prominent complaint (all p < 0.001). Constant pain (coefficient -11.3; p = 0.02), opioid based pain treatment (coefficient -19.7; p < 0.001) and alcoholic aetiology (coefficient -5.1; p = 0.03) were independently associated with lowered global health status. The final multivariable model explained 18% of the variance in global health status. CONCLUSIONS: Patients with CP have significantly lower QOL compared to a population-based reference population. Factors independently associated with a lowered QOL are constant pain, opioid based pain treatment and alcohol aetiology. However, these factors only explain a fraction of QOL and additional factors need identification.

Patient reported exposure to smoking and alcohol abuse are associated with pain and other complications in patients with chronic pancreatitis.

BACKGROUND/OBJECTIVES: Smoking and alcohol abuse are established risk factors for chronic pancreatitis (CP). Few studies have examined how exposure to smoking and alcohol abuse act as risk factors for complications in CP. Our aim was to examine associations between patient reported exposure to smoking and alcohol abuse and complications in CP in a large cohort of patients from the Scandinavian and Baltic countries. METHODS: We retrieved data on demographics, CP related complications and patients' histories of exposure to smoking and alcohol abuse from the Scandinavian Baltic Pancreatic Club database. Associations were investigated by univariate and multivariate logistic regression analyses. Results are presented as odds ratios (OR) with 95% confidence intervals. RESULTS: A complete history of smoking and alcohol exposure was available for 932 patients. In multivariate regression analyses, the presence of pain and exocrine pancreatic insufficiency were both significantly associated with history of smoking (OR 1.94 (1.40-2.68), p < 0.001 and OR 1.89 (1.36-2.62), p < 0.001, respectively) and alcohol abuse (OR 1.66 (1.21-2.26), p = 0.001 and 1.55 (1.14-2.11), p = 0.005, respectively). Smoking was associated with calcifications (OR 2.89 (2.09-3.96), p < 0.001), moderate to severe ductal changes (OR 1.42 (1.05-1.92), p = 0.02), and underweight (OR 4.73 (2.23-10.02), p < 0.001). History of alcohol abuse was associated with pseudocysts (OR 1.38 (1.00-1.90) p = 0.05) and diabetes mellitus (OR 1.44 (1.03-2.01), p = 0.03). There were significantly increased odds-ratios for several complications with increasing exposure to smoking and alcohol abuse. CONCLUSION: Smoking and alcohol abuse are both independently associated with development of complications in patients with CP. There seems to be a dose-dependent relationship between smoking and alcohol abuse and complications in CP.

Association of multiple patient and disease characteristics with the presence and type of pain in chronic pancreatitis.

BACKGROUND AND AIM: 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. METHODS: 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). RESULTS: 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). CONCLUSION: 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 Is Characterized by Distinct Complication Clusters That Associate With Etiological Risk Factors.

OBJECTIVES: Chronic pancreatitis (CP) is characterized by several disease-related complications and multiple etiological risk factors. Past studies of associations between complications and risk factors have mostly been limited to single complications or highly focused on single etiologies. Using an objective data-driven approach (cluster analysis), we characterized complication clusters and their associations with etiological risk factors in a large cohort of patients with CP. METHODS: This was a multicenter, cross-sectional study including 1,071 patients with CP from the Scandinavian and Baltic countries. Complications to CP were classified according to the M-ANNHEIM system, and treelet transform was used to derive complication clusters. Cluster complication frequencies were analyzed for their association with main etiological risk factors (smoking and alcohol). RESULTS: The mean age of participants was 57 years and 66% were men. Alcohol (55%) and smoking (53%) were the most common etiological risk factors and seen in combination in 36% of patients. Cluster analysis identified 3 distinct complication clusters characterized by inflammation, fibrosis, and pancreatic insufficiencies. An independent association between inflammatory complications and alcoholic etiology was seen (odds ratio [OR] 2.00 [95% CI [confidence interval], 1.38-2.90], P < 0.001), whereas smoking was associated with fibrosis-related complications (OR 2.23 [95% CI, 1.56-2.3.20], P < 0.001) and pancreatic insufficiencies (OR 1.42 [95% CI, 1.00-2.01], P = 0.046). DISCUSSION: Three distinctive clusters of complications to CP were identified. Their differing associations with alcoholic and smoking etiology indicate distinct underlying disease mechanisms.

The cost of endoscopic treatment for walled-off pancreatic necrosis.

BACKGROUND: Use of minimally invasive techniques has reduced mortality in walled-off pancreatic necrosis (WON) but may be costly. The aim of this study was to evaluate the actual costs associated with the endoscopic management of patients with WON. METHODS: We included a retrospective cohort of WON patients treated with endoscopic, transgastric drainage and necrosectomy (ETDN) during 2013-2014. Costs were calculated for six sub-areas based on a micro-costing model. Students T-test and non-parametric analysis of variance were performed to evaluate costs in relation to disease etiology and outcome. RESULTS: We included 58 patients (50% men, median age 57 years). The most common etiologies were gallstones (57%) and alcohol (19%). Nine patients (16%) died during admission. The median length of stay was 50 days (IQR 31 days). Eighteen patients (31%) needed treatment in our intensive care unit with a median length of stay of 16 days (IQR 31 days). The mean costs and standard deviation of costs (SD) per patient were: diagnostic imaging $2,431 ($2,301), laboratory tests $3,579 ($2,477), blood products $982 ($1,734), endoscopic treatment $3,794 ($1,777), medicine $5,440 ($6,656), and ward cost $41,260 ($35,854). The mean total cost was $57,486 ($46,739). Post-ERCP pancreatitis and mortality predicted higher costs. CONCLUSIONS: This study sheds light on the different costs associated with endoscopic treatment of WON. As nearly three quarters of the costs are related to ward care, initiatives aimed at reducing the length of hospital stay may have a great impact on making endoscopic treatment more cost effective.

Pulmonary dysfunction due to combination of extra-pulmonary causes and alveolar damage is present from first the day of hospital admission in the early phase of acute pancreatitis.

BACKGROUND: Only few studies have attempted to evaluate the pulmonary function in the early phase of acute pancreatitis (AP), although pulmonary dysfunction is the most frequent complication in the early phase of AP. We aimed to evaluate the changes in pulmonary function tests during the early phase of AP. METHODS: Prospective cohort study including 44 patients (52% men; median age 54 years) admitted with first attack of AP and 22 healthy controls. Patients underwent assessments on day 1, 2, 3, 6, and 10 as well as one month after discharge. Pulmonary function tests included the % predicted: forced expiratory volume during the first second (FEV1), forced vital capacity (FVC), total lung capacity (TLC), diffusion lung capacity (DLCO) and the ratio between DLCO and alveolar volume (DLCO/VA). RESULTS: In total, 9% developed severe acute pancreatitis, 7% died, and 14% required treatment at the intensive or semi-intensive care unit. From admission, patients had impaired FEV1, FVC, DLCO, and TLC compared with controls (p < 0.0001 in all analyses). Patients with CRP >150 mg/L had significantly lower lung function tests. One month after discharge, lung function tests improved but patients had lower FEV1 (p = 0.014), FVC (p = 0.022), TLC (p = 0.020), and DLCO (p < 0.001) compared with controls. CONCLUSION: This study found that patients with AP had evidence of pulmonary impairment from the first day after hospital admission. The impairment lasted several weeks after hospital discharge.

Pancreatic calcifications associate with diverse aetiological risk factors in patients with chronic pancreatitis: A multicentre study of 1500 cases.

BACKGROUND: 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. METHODS: 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. RESULTS: The mean age of patients was 53.9 ±â€¯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). CONCLUSION: 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.

Evaluation of local instillation of antibiotics in infected walled-off pancreatic necrosis.

BACKGROUND: Infected walled-off pancreatic necrosis (WON) is associated with increased morbidity and mortality. Systemic antibiotics are the main treatment, but are associated with adverse reactions and risk of superinfections. This study evaluates the efficacy of local instillation of antibiotics into WON. METHODS: We performed a retrospective cohort study of all consecutive patients with infected WON, who were treated with endoscopic transmural drainage and necrosectomy (ETDN) at a tertiary referral hospital between 2012 and 2016. A total of 91 patients were included. Patients often received concomitant intravenous and local antibiotics. Local antibiotics were added to the irrigation fluid depending on microbiological findings. A beneficial response was defined as the eradication of a microbe on subsequent culturing. Univariable and multivariable logistic regression analyses were used to evaluate antimicrobial efficacy. RESULTS: At the first drainage 81 (86%) patients had infected and 10 sterile WON. Among patients with bacterial infections, neither local nor systemic antibiotics were associated with the eradication of microbes between first and second culture. Between the second and third culture, the use of local antibiotics was associated with the eradication of microbes (OR, 2.54; 95% CI, 1.25-5.18; p = 0.01), but not systemic antibiotics (OR, 0.75; 95% CI, 0.38-1.38; p = 0.33). Twelve patients had fungal infections treated with local amphotericin B between first and second culture. The fungus was eradicated in all 12 patients. CONCLUSION: Local instillation of antibiotics may be a promising supplement to systemic administration.