Importance:The poor prognosis and limited treatment options in patients with locally advanced pancreatic cancer (LAPC) highlight the need for novel therapies to increase survival. Objective:To assess whether the addition of radiofrequency ablation (RFA) to chemotherapy improves survival when compared with chemotherapy only in patients with nonprogressive LAPC. Design, Setting, and Participants:This international randomized clinical trial was performed from April 7, 2015, through December 6, 2022, in patients with unresectable LAPC with at least stable disease after 2 months of induction chemotherapy. The predefined study protocol reported a follow-up period of 18 months. Data analysis was performed from February 1, 2024, through January 15, 2025. Intervention:Randomization to receive either RFA with chemotherapy or chemotherapy alone. Main Outcomes and Measures:Primary outcome was overall survival. Secondary outcomes included progression-free survival, adverse events, and quality of life using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and pancreatic cancer module. Results:Overall, 188 patients (median [IQR] age, 65 [57-70] years; 100 [53%] men) were randomized, 95 to RFA with chemotherapy and 93 to chemotherapy only. Before randomization, induction chemotherapy had consisted of modified FOLFIRINOX (fluorouracil, oxaliplatin, irinotecan, and leucovorin) in 81 patients (85%) and a gemcitabine-based regimen in 14 patients (15%) in the RFA group vs 80 patients (86%) and 13 patients (14%) in the chemotherapy group, respectively. After a median follow-up of 55 months, median overall survival from randomization was 12.1 months (95% CI, 9.9-14.3 months) in the RFA group vs 11.6 months (95% CI, 9.4-13.9 months) in the chemotherapy group (hazard ratio, 1.07; 95% CI, 0.80-1.45; P = .64). Median progression-free survival was 5.8 months (95% CI, 4.4-7.2 months) in the RFA group and 6.9 months (95% CI, 5.3-8.5 months) in the chemotherapy group (P = .47). Grade 3 or higher serious adverse events were reported more often in the RFA group: 26 patients (27%) vs 10 patients (11%) (P = .004). Mean changes from baseline of -14.6, -12.0, and -18.4 were observed for the Global Health Status quality-of-life scores at 1, 3, and 18 months, respectively, numerically exceeding the threshold of 10 points for clinical relevance. In the chemotherapy-only group, mean changes from baseline on the Global Health Status remained below the threshold for clinical relevance. Conclusions and Relevance:This randomized clinical trial of patients with LAPC after 2 months of multiagent chemotherapy found that local ablative therapy with RFA did not improve survival compared with chemotherapy only and adversely affected patient's quality of life. Trial Registration:ClinicalTrials.gov Identifier: NCT03690323.

OBJECTIVES:Infected necrotizing pancreatitis is preferably managed by postponing invasive interventions and, in selected cases, treatment with antibiotics alone. Consequently, microbial cultures are often lacking, possibly increasing the risk of antibiotic treatment failure and unnecessary use of broad-spectrum antibiotics. The main objective was to describe the culture results of fine-needle aspirations (FNA) in a retrospective cohort of necrotizing pancreatitis patients, and relate this to the administered empirical antibiotic regimen to explore FNA's potential clinical value. METHODS:Post hoc analysis of a cohort of 618 patients hospitalized with acute necrotizing pancreatitis in 17 Dutch hospitals (2010-2020). RESULTS:Of 618 acute necrotizing pancreatitis patients, 68 (11%) underwent 71 FNA procedures: 11 (15%) endoscopic and 60 (85%) percutaneous. Three patients underwent repeated FNA procedures. Most FNA samples (75%) were culture-positive, all endoscopic FNA were polymicrobial (versus 27% in percutaneous FNA) and therefore suspect for contamination. Among 22 patients who received antimicrobial therapy before percutaneous FNA, 4 (18%) grew pathogens not susceptible to the administered antibiotics. Resistance in positive samples to common Dutch empirical regimens was 28% for cephalosporin/metronidazole, 19% for piperacillin-tazobactam and 21% for meropenem. No periprocedural complications occurred. CONCLUSIONS:This study suggests that diagnostic percutaneous FNA is a safe procedure with no observed complications, that may be useful in guiding antimicrobial therapy in patients with infected necrotizing pancreatitis, especially when delaying or omitting drainage procedures. Prospective studies and clinical trials are needed to confirm this. Percutaneous FNA is preferred over endoscopic FNA, as the latter carries a high risk of sample contamination.

QuestionCan the addition of radiofrequency ablation (RFA) to chemotherapy improve survival compared with chemotherapy only in patients with nonprogressive locally advanced pancreatic cancer (LAPC) after 2 months of multiagent chemotherapy?FindingsThis international randomized clinical trial, including 188 patients with LAPC after 2 months of multiagent chemotherapy, found that local ablative therapy with RFA did not improve survival compared with chemotherapy only and worsened quality of life.MeaningThe findings in this trial provide evidence against the use of RFA after chemotherapy in patients with LAPC. This randomized clinical trial evaluates the efficacy of radiofrequency ablation (RFA) and chemotherapy compared with chemotherapy only in patients with locally advanced pancreatic cancer. ImportanceThe poor prognosis and limited treatment options in patients with locally advanced pancreatic cancer (LAPC) highlight the need for novel therapies to increase survival.ObjectiveTo assess whether the addition of radiofrequency ablation (RFA) to chemotherapy improves survival when compared with chemotherapy only in patients with nonprogressive LAPC.Design, Setting, and ParticipantsThis international randomized clinical trial was performed from April 7, 2015, through December 6, 2022, in patients with unresectable LAPC with at least stable disease after 2 months of induction chemotherapy. The predefined study protocol reported a follow-up period of 18 months. Data analysis was performed from February 1, 2024, through January 15, 2025.InterventionRandomization to receive either RFA with chemotherapy or chemotherapy alone.Main Outcomes and MeasuresPrimary outcome was overall survival. Secondary outcomes included progression-free survival, adverse events, and quality of life using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and pancreatic cancer module.ResultsOverall, 188 patients (median [IQR] age, 65 [57-70] years; 100 [53%] men) were randomized, 95 to RFA with chemotherapy and 93 to chemotherapy only. Before randomization, induction chemotherapy had consisted of modified FOLFIRINOX (fluorouracil, oxaliplatin, irinotecan, and leucovorin) in 81 patients (85%) and a gemcitabine-based regimen in 14 patients (15%) in the RFA group vs 80 patients (86%) and 13 patients (14%) in the chemotherapy group, respectively. After a median follow-up of 55 months, median overall survival from randomization was 12.1 months (95% CI, 9.9-14.3 months) in the RFA group vs 11.6 months (95% CI, 9.4-13.9 months) in the chemotherapy group (hazard ratio, 1.07; 95% CI, 0.80-1.45; P = .64). Median progression-free survival was 5.8 months (95% CI, 4.4-7.2 months) in the RFA group and 6.9 months (95% CI, 5.3-8.5 months) in the chemotherapy group (P = .47). Grade 3 or higher serious adverse events were reported more often in the RFA group: 26 patients (27%) vs 10 patients (11%) (P = .004). Mean changes from baseline of -14.6, -12.0, and -18.4 were observed for the Global Health Status quality-of-life scores at 1, 3, and 18 months, respectively, numerically exceeding the threshold of 10 points for clinical relevance. In the chemotherapy-only group, mean changes from baseline on the Global Health Status remained below the threshold for clinical relevance.Conclusions and RelevanceThis randomized clinical trial of patients with LAPC after 2 months of multiagent chemotherapy found that local ablative therapy with RFA did not improve survival compared with chemotherapy only and adversely affected patient's quality of life.Trial RegistrationClinicalTrials.gov Identifier: NCT03690323

BACKGROUND:In expert centres, surgical resection rates for patients with locally advanced pancreatic cancer (LAPC) after induction chemotherapy have increased beyond 20% with subsequent 25% 5-year overall survival (OS). In the Netherlands, however, the historical low 8% LAPC resection rate compared with 23% in international expert centres reflects a relative reluctance to perform resections. Thereby, opportunities to achieve long-term survival in appropriately selected patients may be missed. The aim of this study was to evaluate whether nationwide implementation of international multidisciplinary best practice for LAPC management is feasible while maintaining surgical safety benchmarks (in-hospital/30-day major morbidity <50% and mortality ≤5%). METHODS:A multidisciplinary protocol was designed in collaboration with four international experts and prospectively implemented nationwide within the Dutch Pancreatic Cancer Group (DPCG) (2022-2024). This observational cohort included consecutive patients diagnosed with LAPC, defined by DPCG criteria. Eligible patients had radiologically non-progressive disease after ≥4 months of multiagent chemotherapy. All patients who underwent resection were included in this safety analysis. A predefined subgroup analysis included patients with National Comprehensive Cancer Network (NCCN) LAPC. Primary outcomes included in-hospital/30-day major morbidity (that is Clavien-Dindo grade ≥IIIa) and mortality. The expected number of resections was 53. RESULTS:Overall, 180 patients with LAPC underwent surgical exploration, of whom 155 (86%) underwent resection in 11 centres. Most resections (74%) were performed in the three LAPC surgical centres. An extended resection was performed for 77% of patients, including portomesenteric venous (60%), multivisceral (23%), and arterial (21%) resections. The in-hospital/30-day major morbidity rate was 44% and the mortality rate was 0.6%, both within pre-established safety benchmarks. Benchmarks were also reached for patients with NCCN LAPC (49% major morbidity and 2% mortality). CONCLUSION:Nationwide implementation of the international best practice for LAPC was feasible with nearly three times more resections performed than expected, while morbidity and mortality remained well within predefined safety benchmarks.

IMPORTANCE Patients with painful chronic pancreatitis and a dilated pancreatic duct can be treated by early surgery or an endoscopy-first approach. OBJECTIVE To compare long-term clinical outcomes of early surgery vs an endoscopy-first approach using follow-up data from the ESCAPE randomized clinical trial. DESIGN, SETTING, AND PARTICIPANTS Between April 2011 and September 2018, 88 patients with painful chronic pancreatitis were randomly assigned to early surgery or an endoscopy-first approach in 30 hospitals in the Netherlands collaborating in the Dutch Pancreatitis Study Group as part of the ESCAPE randomized clinical trial. For the present cohort study, long-term clinical data were collected after the initial 18-month follow-up. Follow-up was completed in June 2022, and data analysis was performed in June 2023. EXPOSURE Patients with chronic pancreatitis were randomly assigned to early surgery or an endoscopy-first approach. MAIN OUTCOMES AND MEASURES The primary end point was pain, assessed by the Izbicki pain score; secondary end points included patient-reported complete pain relief and satisfaction. Predefined subgroups included patients who progressed from endoscopy to surgery and those with ductal clearance obtained by endoscopy. Analysis was performed according to the intention-to-treat principle. RESULTS In this cohort study, 86 of 88 overall patients could be evaluated, with a mean (SD) follow-up period of 98 (16) months. Of 88 initial patients, 21 patients (24%) were female, and mean (SD) patient age was 61(10) years. At the end of long-term follow-up, the mean (SD) Izbicki pain score was significant lower (33 [31] vs 51 [31]) in the early surgery group, as was the rate of patient-reported complete pain relief (14 of 31 patients [45%] vs 6 of 30 patients [20%]), compared to the endoscopy-first group. After the initial 18-month follow-up, 11 of 43 patients in the early surgery group (26%) underwent reinterventions vs 19 of 43 patients in the endoscopy-first group (44%). At the end of follow-up, more patients in the early surgery group were "very satisfied" with their treatment (22 of 31 patients [71%] vs 10 of 30 patients [33%]). Patients who progressed from endoscopy to surgery (22 of 43 patients [51%]) had significantly worse mean (SD) Izbicki pain scores (33 [31] vs 52 [24]) compared to the early surgery group and had a lower rate of complete pain relief (55% for early surgery vs 12% for endoscopy first). In the endoscopy-first group, patients with endoscopic ductal clearance had similar mean (SD) Izbicki pain scores as the remaining patients (49 [34] vs 53 [28]). CONCLUSIONS AND RELEVANCE In this cohort study evaluating long-term outcomes of the ESCAPE randomized clinical trial, after approximately 8 years of follow-up, early surgery was superior to an endoscopy-first approach in patients with painful chronic pancreatitis and a dilated main pancreatic duct in pain scores and patient satisfaction. Notably, patients who progressed from endoscopy to surgery had worse outcomes compared to patients undergoing early surgery, and obtaining endoscopic ductal clearance did not improve outcomes.

To identify predictors for successful treatment of patients with infected necrotizing pancreatitis with antibiotics alone. Infected necrotizing pancreatitis is associated with mortality ranging from 15% to 35%. Recent studies have shown that in some patients, treatment with antibiotics alone is successful, thus avoiding invasive procedures. We performed a post hoc analysis of a prospective cohort of 305 patients with suspected or proven infected necrotizing pancreatitis from 22 Dutch hospitals. The primary outcome was successful treatment with antibiotics alone (ie, survival without radiologic, endoscopic, or surgical intervention). All computed tomography images were reviewed to classify the pattern of pancreatic necrosis. A prediction model using clinical and radiologic predictors was created using multivariable logistic regression. A prognostic nomogram was developed based on the final predictors. Overall, 86 out of 305 patients (28%) with infected necrotizing pancreatitis were successfully treated with antibiotics alone. Our final prediction model included presence of organ failure at the start of antibiotics [odds ratio (OR): 0.46, 95% CI: 0.22–0.99, P=0.046], presence of central necrosis (OR: 0.11, 95% CI: 0.05–0.23, P<0.001) and presence of subtotal necrosis (OR: 0.12, 95% CI: 0.03–0.36, P<0.001). The area under the curve was 0.74 (95% CI: 0.70–0.75). The prognostic nomogram yielded a probability of successful antibiotic treatment of 5% when organ failure and central necrosis were present and 47% when all predictors were absent. In patients with infected necrotizing pancreatitis, predictors negatively impacting successful treatment with antibiotics are organ failure at the start of antibiotics, and the presence of central or subtotal necrosis on imaging.

ImportancePatients with painful chronic pancreatitis and a dilated pancreatic duct can be treated by early surgery or an endoscopy-first approach.ObjectiveTo compare long-term clinical outcomes of early surgery vs an endoscopy-first approach using follow-up data from the ESCAPE randomized clinical trial.Design, Setting, and ParticipantsBetween April 2011 and September 2018, 88 patients with painful chronic pancreatitis were randomly assigned to early surgery or an endoscopy-first approach in 30 hospitals in the Netherlands collaborating in the Dutch Pancreatitis Study Group as part of the ESCAPE randomized clinical trial. For the present cohort study, long-term clinical data were collected after the initial 18-month follow-up. Follow-up was completed in June 2022, and data analysis was performed in June 2023.ExposurePatients with chronic pancreatitis were randomly assigned to early surgery or an endoscopy-first approach.Main Outcomes and MeasuresThe primary end point was pain, assessed by the Izbicki pain score; secondary end points included patient-reported complete pain relief and satisfaction. Predefined subgroups included patients who progressed from endoscopy to surgery and those with ductal clearance obtained by endoscopy. Analysis was performed according to the intention-to-treat principle.ResultsIn this cohort study, 86 of 88 overall patients could be evaluated, with a mean (SD) follow-up period of 98 (16) months. Of 88 initial patients, 21 patients (24%) were female, and mean (SD) patient age was 61 (10) years. At the end of long-term follow-up, the mean (SD) Izbicki pain score was significant lower (33 [31] vs 51 [31]) in the early surgery group, as was the rate of patient-reported complete pain relief (14 of 31 patients [45%] vs 6 of 30 patients [20%]), compared to the endoscopy-first group. After the initial 18-month follow-up, 11 of 43 patients in the early surgery group (26%) underwent reinterventions vs 19 of 43 patients in the endoscopy-first group (44%). At the end of follow-up, more patients in the early surgery group were “very satisfied” with their treatment (22 of 31 patients [71%] vs 10 of 30 patients [33%]). Patients who progressed from endoscopy to surgery (22 of 43 patients [51%]) had significantly worse mean (SD) Izbicki pain scores (33 [31] vs 52 [24]) compared to the early surgery group and had a lower rate of complete pain relief (55% for early surgery vs 12% for endoscopy first). In the endoscopy-first group, patients with endoscopic ductal clearance had similar mean (SD) Izbicki pain scores as the remaining patients (49 [34] vs 53 [28]).Conclusions and RelevanceIn this cohort study evaluating long-term outcomes of the ESCAPE randomized clinical trial, after approximately 8 years of follow-up, early surgery was superior to an endoscopy-first approach in patients with painful chronic pancreatitis and a dilated main pancreatic duct in pain scores and patient satisfaction. Notably, patients who progressed from endoscopy to surgery had worse outcomes compared to patients undergoing early surgery, and obtaining endoscopic ductal clearance did not improve outcomes.

OBJECTIVE:To identify predictors for successful treatment of patients with infected necrotizing pancreatitis with antibiotics alone. BACKGROUND:Infected necrotizing pancreatitis is associated with mortality ranging from 15% to 35%. Recent studies have shown that in some patients, treatment with antibiotics alone is successful, thus avoiding invasive procedures. METHODS:We performed a post hoc analysis of a prospective cohort of 305 patients with suspected or proven infected necrotizing pancreatitis from 22 Dutch hospitals. The primary outcome was successful treatment with antibiotics alone (ie, survival without radiologic, endoscopic, or surgical intervention). All computed tomography images were reviewed to classify the pattern of pancreatic necrosis. A prediction model using clinical and radiologic predictors was created using multivariable logistic regression. A prognostic nomogram was developed based on the final predictors. RESULTS:Overall, 86 out of 305 patients (28%) with infected necrotizing pancreatitis were successfully treated with antibiotics alone. Our final prediction model included presence of organ failure at the start of antibiotics [odds ratio (OR): 0.46, 95% CI: 0.22-0.99, P =0.046], presence of central necrosis (OR: 0.11, 95% CI: 0.05-0.23, P <0.001) and presence of subtotal necrosis (OR: 0.12, 95% CI: 0.03-0.36, P <0.001). The area under the curve was 0.74 (95% CI: 0.70-0.75). The prognostic nomogram yielded a probability of successful antibiotic treatment of 5% when organ failure and central necrosis were present and 47% when all predictors were absent. CONCLUSIONS:In patients with infected necrotizing pancreatitis, predictors negatively impacting successful treatment with antibiotics are organ failure at the start of antibiotics, and the presence of central or subtotal necrosis on imaging.

BACKGROUND:Treatment guidelines for splanchnic vein thrombosis in necrotizing pancreatitis are lacking due to insufficient data on the full clinical spectrum. METHODS:We performed a post-hoc analysis of a nationwide prospective necrotizing pancreatitis cohort. Multivariable analyses were used to identify risk factors and compare the clinical course of patients with and without SVT. RESULTS:SVT was detected in 97 of the 432 included patients (22%) (median onset: 4 days). Risk factors were left, central, or subtotal necrosis (OR 28.52; 95% CI 20.11-40.45), right or diffuse necrosis (OR 5.76; 95% CI 3.89-8.51), and younger age (OR 0.94; 95% CI 0.90-0.97). Patients with SVT had higher rates of bleeding (n = 10,11%) and bowel ischemia (n = 4,4%) compared to patients without SVT (n = 14,4% and n = 2,0.6%; OR 3.24; 95% CI 1.27-8.23 and OR 7.29; 95% CI 1.31-40.4, respectively), and were independently associated with ICU admission (adjusted OR 2.53; 95% CI 1.37-4.68). Spontaneous recanalization occurred in 62% of patients (n = 40/71). Radiological and clinical outcomes did not differ between patients treated with and without anticoagulants. DISCUSSION:SVT is a common and early complication of necrotizing pancreatitis, associated with parenchymal necrosis and younger age. SVT is associated with increased complications and a worse clinical course, whereas anticoagulant use does not appear to affect outcomes.

Objective To describe the long-term consequences of necrotising pancreatitis, including complications, the need for interventions and the quality of life. Design Long-term follow-up of a prospective multicentre cohort of 373 necrotising pancreatitis patients (2005-2008) was performed. Patients were prospectively evaluated and received questionnaires. Readmissions (ie, for recurrent or chronic pancreatitis), interventions, pancreatic insufficiency and quality of life were compared between initial treatment groups: conservative, endoscopic/percutaneous drainage alone and necrosectomy. Associations of patient and disease characteristics during index admission with outcomes during follow-up were assessed. Results During a median follow-up of 13.5 years (range 12-15.5 years), 97/373 patients (26%) were readmitted for recurrent pancreatitis. Endoscopic or percutaneous drainage was performed in 47/373 patients (13%), of whom 21/47 patients (45%) were initially treated conservatively. Pancreatic necrosectomy or pancreatic surgery was performed in 31/373 patients (8%), without differences between treatment groups. Endocrine insufficiency (126/373 patients; 34%) and exocrine insufficiency (90/373 patients; 38%), developed less often following conservative treatment (p<0.001 and p=0.016, respectively). Quality of life scores did not differ between groups. Pancreatic gland necrosis >50% during initial admission was associated with percutaneous/endoscopic drainage (OR 4.3 (95% CI 1.5 to 12.2)), pancreatic surgery (OR 3.2 (95% CI 1.1 to 9.5) and development of endocrine insufficiency (OR13.1 (95% CI 5.3 to 32.0) and exocrine insufficiency (OR6.1 (95% CI 2.4 to 15.5) during follow-up. Conclusion Acute necrotising pancreatitis carries a substantial disease burden during long-term follow-up in terms of recurrent disease, the necessity for interventions and development of pancreatic insufficiency, even when treated conservatively during the index admission. Extensive (>50%) pancreatic parenchymal necrosis seems to be an important predictor of interventions and complications during follow-up.

Background: Pelvic insufficiency fractures (PIFs) are a late complication of radiotherapy for pelvic malignancies. We evaluated the incidence, radiologic findings, clinical course, and outcome of PIFs in patients treated with neoadjuvant (chemo)radiotherapy ((C)RT) for rectal cancer.Material and methods: Data of patients diagnosed with rectal cancer from a large teaching hospital treated from 2002 to 2012 were extracted from the Dutch Cancer Registry. All hospital records were reviewed for the diagnosis of PIFs or pelvic bone metastases. An expert radiologist reassessed all imaging procedures of the lower back, abdomen, and pelvis.Results: A total of 513 rectal cancer patients were identified of whom 300 patients (58.5%) were treated with neoadjuvant (C)RT (long- vs. short-course radiotherapy: 91 patients [17.7%] vs. 209 [40.7%], respectively). Twelve PIFs were diagnosed initially according to hospital records and imaging reports of all 513 patients. These 12 patients were treated with neoadjuvant (C)RT. After reassessment of all pelvic imaging procedures done in this patient group (432 patients (84.2%)), 20 additional PIFs were detected in patients treated with neoadjuvant (C)RT, resulting in a 10.7% PIF rate in irradiated patients. One PIF was detected in the group of patients not treated with neoadjuvant (C)RT for rectal cancer. This patient had palliative radiotherapy for prostate cancer and is left out of the analysis. Median follow-up time of 32 PIF patients was 49 months. Median time between start of neoadjuvant (C)RT and diagnosis of PIF was 17 months (IQR 9-28). Overall median survival for patients with PIF was 63.5 months (IQR 44-120).Conclusion: PIFs are a relatively common late complication of neoadjuvant (C)RT for rectal cancer but are often missed or misdiagnosed as pelvic bone metastases. The differentiation of PIFs from pelvic bone metastases is important because of a different treatment and disease outcome.

Objective: The use and impact of antibiotics and the impact of causative pathogens on clinical outcomes in a large real-world cohort covering the entire clinical spectrum of necrotizing pancreatitis remain unknown. Summary Background Data: International guidelines recommend broad-spectrum antibiotics in patients with suspected infected necrotizing pancreatitis. This recommendation is not based on high-level evidence and clinical effects are unknown. Materials and Methods: This study is a post-hoc analysis of a nationwide prospective cohort of 401 patients with necrotizing pancreatitis in 15 Dutch centers (2010-2019). Across the patient population from the time of admission to 6 months postadmission, multivariable regression analyses were used to analyze (1) microbiological cultures and (2) antibiotic use. Results: Antibiotics were started in 321/401 patients (80%) administered at a median of 5 days (P25-P75: 1-13) after admission. The median duration of antibiotics was 27 days (P25-P75: 15-48). In 221/321 patients (69%) infection was not proven by cultures at the time of initiation of antibiotics. Empirical antibiotics for infected necrosis provided insufficient coverage in 64/128 patients (50%) with a pancreatic culture. Prolonged antibiotic therapy was associated with Enterococcus infection (OR 1.08 [95% CI 1.03-1.16], P=0.01). Enterococcus infection was associated with new/persistent organ failure (OR 3.08 [95% CI 1.35-7.29], P<0.01) and mortality (OR 5.78 [95% CI 1.46-38.73], P=0.03). Yeast was found in 30/147 cultures (20%). Discussion: In this nationwide study of patients with necrotizing pancreatitis, the vast majority received antibiotics, typically administered early in the disease course and without a proven infection. Empirical antibiotics were inappropriate based on pancreatic cultures in half the patients. Future clinical research and practice must consider antibiotic selective pressure due to prolonged therapy and coverage of Enterococcus and yeast. Improved guidelines on antimicrobial diagnostics and therapy could reduce inappropriate antibiotic use and improve clinical outcomes.

BACKGROUND Splanchnic vein thrombosis (SVT) is a major complication of moderate and severe acute pancreatitis. There is no consensus on whether therapeutic anticoagulation should be started in patients with acute pancreatitis and SVT. AIM To gain insight into current opinions and clinical decision making of pancreatologists regarding SVT in acute pancreatitis. METHODS A total of 139 pancreatologists of the Dutch Pancreatitis Study Group and Dutch Pancreatic Cancer Group were approached to complete an online survey and case vignette survey. The threshold to assume group agreement was set at 75%. RESULTS The response rate was 67% (n = 93). Seventy-one pancreatologists (77%) regularly prescribed therapeutic anticoagulation in case of SVT, and 12 pancreatologists (13%) for narrowing of splanchnic vein lumen. The most common reason to treat SVT was to avoid complications (87%). Acute thrombosis was the most important factor to prescribe therapeutic anticoagulation (90%). Portal vein thrombosis was chosen as the most preferred location to initiate therapeutic anticoagulation (76%) and splenic vein thrombosis as the least preferred location (86%). The preferred initial agent was low molecular weight heparin (LMWH; 87%). In the case vignettes, therapeutic anticoagulation was prescribed for acute portal vein thrombosis, with or without suspected infected necrosis (82% and 90%), and thrombus progression (88%). Agreement was lacking regarding the selection and duration of long-term anticoagulation, the indication for thrombophilia testing and upper endoscopy, and about whether risk of bleeding is a major barrier for therapeutic anticoagulation. CONCLUSION In this national survey, the pancreatologists seemed to agree on the use of therapeutic anticoagulation, using LMWH in the acute phase, for acute portal thrombosis and in the case of thrombus progression, irrespective of the presence of infected necrosis.

ObjectiveRoutine urgent endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic biliary sphincterotomy (ES) does not improve outcome in patients with predicted severe acute biliary pancreatitis. Improved patient selection for ERCP by means of endoscopic ultrasonography (EUS) for stone/sludge detection may challenge these findings.DesignA multicentre, prospective cohort study included patients with predicted severe acute biliary pancreatitis without cholangitis. Patients underwent urgent EUS, followed by ERCP with ES in case of common bile duct stones/sludge, within 24 hours after hospital presentation and within 72 hours after symptom onset. The primary endpoint was a composite of major complications or mortality within 6 months after inclusion. The historical control group was the conservative treatment arm (n=113) of the randomised APEC trial (Acute biliary Pancreatitis: urgent ERCP with sphincterotomy versus conservative treatment, patient inclusion 2013–2017) applying the same study design.ResultsOverall, 83 patients underwent urgent EUS at a median of 21 hours (IQR 17–23) after hospital presentation and at a median of 29 hours (IQR 23–41) after start of symptoms. Gallstones/sludge in the bile ducts were detected by EUS in 48/83 patients (58%), all of whom underwent immediate ERCP with ES. The primary endpoint occurred in 34/83 patients (41%) in the urgent EUS-guided ERCP group. This was not different from the 44% rate (50/113 patients) in the historical conservative treatment group (risk ratio (RR) 0.93, 95% CI 0.67 to 1.29; p=0.65). Sensitivity analysis to correct for baseline differences using a logistic regression model also showed no significant beneficial effect of the intervention on the primary outcome (adjusted OR 1.03, 95% CI 0.56 to 1.90, p=0.92).ConclusionIn patients with predicted severe acute biliary pancreatitis without cholangitis, urgent EUS-guided ERCP with ES did not reduce the composite endpoint of major complications or mortality, as compared with conservative treatment in a historical control group.Trial registration numberISRCTN15545919.

Objective: The aim of this study was to explore the incidence, risk factors, clinical course and treatment of perforation and fistula of the gastrointestinal (GI) tract in a large unselected cohort of patients with necrotizing pancreatitis. Background: Perforation and fistula of the GI tract may occur in necrotizing pancreatitis. Data from large unselected patient populations on the incidence, risk factors, clinical outcomes, and treatment are lacking. Methods: We performed a post hoc analysis of a nationwide prospective database of 896 patients with necrotizing pancreatitis. GI tract perforation and fistula were defined as spontaneous or iatrogenic discontinuation of the GI wall. Multivariable logistic regression was used to explore risk factors and to adjust for confounders to explore associations of the GI tract perforation and fistula on the clinical course. Results: A perforation or fistula of the GI tract was identified in 139 (16%) patients, located in the stomach in 23 (14%), duodenum in 56 (35%), jejunum or ileum in 18 (11%), and colon in 64 (40%). Risk factors were high C-reactive protein within 48 hours after admission [odds ratio (OR): 1.19; 95% confidence interval (CI): 1.01–1.39] and early organ failure (OR: 2.76; 95% CI: 1.78–4.29). Prior invasive intervention was a risk factor for developing a perforation or fistula of the lower GI tract (OR: 2.60; 95% CI: 1.04–6.60). While perforation or fistula of the upper GI tract appeared to be protective for persistent intensive care unit-admission (OR: 0.11, 95% CI: 0.02–0.44) and persistent organ failure (OR: 0.15; 95% CI: 0.02–0.58), perforation or fistula of the lower GI tract was associated with a higher rate of new onset organ failure (OR: 2.47; 95% CI: 1.23–4.84). When the stomach or duodenum was affected, treatment was mostly conservative (n=54, 68%). Treatment was mostly surgical when the colon was affected (n=38, 59%). Conclusions: Perforation and fistula of the GI tract occurred in one out of six patients with necrotizing pancreatitis. Risk factors were high C-reactive protein within 48 hours and early organ failure. Prior intervention was identified as a risk factor for perforation or fistula of the lower GI tract. The clinical course was mostly affected by involvement of the lower GI tract.

ObjectiveLumen-apposing metal stents (LAMS) are believed to clinically improve endoscopic transluminal drainage of infected necrosis when compared with double-pigtail plastic stents. However, comparative data from prospective studies are very limited.DesignPatients with infected necrotising pancreatitis, who underwent an endoscopic step-up approach with LAMS within a multicentre prospective cohort study were compared with the data of 51 patients in the randomised TENSION trial who had been assigned to the endoscopic step-up approach with double-pigtail plastic stents. The clinical study protocol was otherwise identical for both groups. Primary end point was the need for endoscopic transluminal necrosectomy. Secondary end points included mortality, major complications, hospital stay and healthcare costs.ResultsA total of 53 patients were treated with LAMS in 16 hospitals during 27 months. The need for endoscopic transluminal necrosectomy was 64% (n=34) and was not different from the previous trial using plastic stents (53%, n=27)), also after correction for baseline characteristics (OR 1.21 (95% CI 0.45 to 3.23)). Secondary end points did not differ between groups either, which also included bleeding requiring intervention—5 patients (9%) after LAMS placement vs 11 patients (22%) after placement of plastic stents (relative risk 0.44; 95% CI 0.16 to 1.17). Total healthcare costs were also comparable (mean difference −€6348, bias-corrected and accelerated 95% CI −€26 386 to €10 121).ConclusionOur comparison of two patient groups from two multicentre prospective studies with a similar design suggests that LAMS do not reduce the need for endoscopic transluminal necrosectomy when compared with double-pigtail plastic stents in patients with infected necrotising pancreatitis. Also, the rate of bleeding complications was comparable.