Intestine

N Engl J Med. 2021;385(14):1280–91

Sandborn WJ, Feagan BG, D'Haens G, Wolf DC, Jovanovic I, Hanauer SB, Ghosh S, Petersen A, Hua SY, Lee JH, Charles L, Chitkara D, Usiskin K, Colombel JF, Laine L, Danese S; True North Study Group

Ozanimod as induction and maintenance therapy for ulcerative colitis

Background: Ozanimod, a selective sphingosine-1-phosphate receptor modulator, is under investigation for the treatment of inflammatory bowel disease.
Methods: The authors conducted a phase 3, multicenter, randomized, double-blind, placebo-controlled trial of ozanimod as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. In the 10-week induction period, patients in cohort 1 were assigned to receive oral ozanimod hydrochloride at a dose of 1 mg (equivalent to 0.92 mg of ozanimod) or placebo once daily in a double-blind manner, and patients in cohort 2 received open-label ozanimod at the same daily dose. At 10 weeks, patients with a clinical response to ozanimod in either cohort underwent randomization again to receive double-blind ozanimod or placebo for the maintenance period (through week 52). The primary end point for both periods was the percentage of patients with clinical remission, as assessed with the 3-component Mayo score. Key secondary clinical, endoscopic, and histologic end points were evaluated with the use of ranked, hierarchical testing. Safety was also assessed.
Results: In the induction period, 645 patients were included in cohort 1 and 367 in cohort 2; a total of 457 patients were included in the maintenance period. The incidence of clinical remission was significantly higher among patients who received ozanimod than among those who received placebo during both induction (18.4% vs. 6.0%, p < 0.001) and maintenance (37.0% vs. 18.5% [among patients with a response at week 10], p < 0.001). The incidence of clinical response was also significantly higher with ozanimod than with placebo during induction (47.8% vs. 25.9%, p < 0.001) and maintenance (60.0% vs. 41.0%, p < 0.001). All other key secondary end points were significantly improved with ozanimod as compared with placebo in both periods. The incidence of infection (of any severity) with ozanimod was similar to that with placebo during induction and higher than that with placebo during maintenance. Serious infection occurred in less than 2% of the patients in each group during the 52-week trial. Elevated liver aminotransferase levels were more common with ozanimod.

Conclusions: Ozanimod was more effective than placebo as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis.

W.J. Sandborn, M.D., Professor of Medicine, Division of Gastroenterology, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0956, USA,

E-Mail: wsandborn@ucsd.edu

Gastroenterology. 2021;161(4):1168–78

Fleischmann C, Probst A, Ebigbo A, Faiss S, Schumacher B, Allgaier HP, Dumoulin FL, Steinbrueck I, Anzinger M, Marienhagen J, Muzalyova A, Messmann H

Endoscopic submucosal dissection in Europe: Results of 1000 neoplastic lesions from the German endoscopic submucosal dissection registry

Background and aims: Endoscopic submucosal dissection (ESD) enables the curative resection of early malignant lesions and is associated with reduced recurrence risk. Due to the lack of comprehensive ESD data in the West, the German ESD registry was set up to evaluate relevant outcomes of ESD.
Methods: The German ESD registry is a prospective uncontrolled multicenter study. During a 35-month period, 20 centers included 1000 ESDs of neoplastic lesions. The results were evaluated in terms of en bloc, R0, curative resection rates, and recurrence rate after a 3-month and 12-month follow-up. Additionally, participating centers were grouped into low-volume (≤ 20 ESDs/year), middle-volume (20–50/year), and high-volume centers (> 50/year). A multivariate analysis investigating risk factors for non-curative resection was performed.
Results: Overall, en bloc, R0, and curative resection rates of 92.4% (95% confidence interval [CI]: 0.90–0.94), 78.8% (95% CI: 0.76–0.81), and 72.3% (95% CI: 0.69–0.75) were achieved, respectively. The overall complication rate was 8.3% (95% CI: 0.067–0.102), whereas the recurrence rate after 12 months was 2.1%. High-volume centers had significantly higher en bloc, R0, curative resection rates, and recurrence rates and lower complication rates than middle- or low-volume centers. The lesion size, hybrid ESD, age, stage T1b carcinoma, and treatment outside high-volume centers were identified as risk factors for non-curative ESD.

Conclusion: In Germany, endoscopic submucosal dissection (ESD) achieves excellent en bloc resection rates but only modest curative resection rates. ESD requires a high level of expertise, and results vary significantly depending on the center's yearly case volume.

Prof. Dr. H. Messmann, III. Medizinische Klinik, Universitätsklinikum Augsburg, Stenglinstr. 2, 86156 Augsburg, Germany,

E-Mail: helmut.messmann@uk-augsburg.de

Gut. 2021;70(11):2076–84

Lu TX, Dapas M, Lin E, Peters T, Sakuraba A

The influence of proton-pump inhibitor therapy on the outcome of infliximab therapy in inflammatory bowel disease: A patient-level meta-analysis of randomized controlled studies

Objective: In treating patients with inflammatory bowel disease (IBD), how concomitant medications influence the response to infliximab is largely unexplored. The aim of this study was to evaluate whether proton-pump inhibitors (PPIs) affect the response to infliximab therapy in patients with IBD.
Design: Patient-level data of adult patients with moderate-to-severe IBD treated with infliximab were obtained from the Yale Open Data Access Framework. Multivariable analysis and propensity score-matched analysis were performed to assess week 30 remission rates, week 54 remission rates and hospitalization rates in patients on infliximab therapy with and without PPI exposure.
Results: Among the 5 randomized controlled studies, there were 147 and 889 patients on infliximab with and without PPI therapy, respectively. Patients on PPI were older, more likely to be Caucasian and were less likely to be on immunomodulator therapy. Patients on PPI were significantly less likely to achieve week 30 remission on multivariable analysis (odds ratio = 0.45, p < 0.001). Following propensity score matching adjusting for baseline difference in patient characteristics, the week 30 remission rates were 30% and 49% in patients with and without PPI therapy, respectively (p < 0.001). Analyzing separately for disease, the findings remained statistically significant in Crohn's disease but did not reach significance in ulcerative colitis. Similar results were seen with week 54 remission rates. Patients on PPI were also more likely to be hospitalized (15% vs. 8%, p = 0.007). Rates of adverse events such as gastroenteritis were not different between the 2 groups.

Conclusion: In this patient-level meta-analysis of randomized controlled studies, the authors found that patients with inflammatory bowel disease (IBD) taking proton-pump inhibitors (PPIs) were less likely to achieve remission while on infliximab therapy. The results of this study warrant further investigation into the effect of PPIs on IBD outcomes and therapies.

A. Sakuraba, M.D., Ph.D., Associate Professor of Medicine, Inflammatory Bowel Disease Center, University of Chicago Medicine, 5841 S. Maryland Avenue, Chicago, IL 60637, USA,

E-Mail: asakurab@medicine.bsd.uchicago.edu

N Engl J Med. 2021;385(17):1559–69

Sanyal AJ, Van Natta ML, Clark J, Neuschwander-Tetri BA, Diehl AM, Dasarathy S, Loomba R, Chalasani N, Kowdley K, Hameed B, Wilson LA, Yates KP, Belt P, Lazo M, Kleiner DE, Behling C, Tonascia J; NASH Clinical Research Network (CRN)

Prospective study of outcomes in adults with non-alcoholic fatty liver disease

Background: The prognoses with respect to mortality and hepatic and non-hepatic outcomes across the histologic spectrum of non-alcoholic fatty liver disease (NAFLD) are not well defined.
Methods: The authors prospectively followed a multicenter patient population that included the full histologic spectrum of NAFLD. The incidences of death and other outcomes were compared across baseline histologic characteristics.
Results: A total of 1773 adults with NAFLD were followed for a median of 4 years. All-cause mortality increased with increasing fibrosis stages (0.32 deaths per 100 person-years for stage F0 to F2 [no, mild, or moderate fibrosis], 0.89 deaths per 100 persons-years for stage F3 [bridging fibrosis], and 1.76 deaths per 100 person-years for stage F4 [cirrhosis]). The incidence of liver-related complications per 100 person-years increased with fibrosis stage (F0 to F2 vs. F3 vs. F4) as follows: variceal hemorrhage (0.00 vs. 0.06 vs. 0.70), ascites (0.04 vs. 0.52 vs. 1.20), encephalopathy (0.02 vs. 0.75 vs. 2.39), and hepatocellular cancer (0.04 vs. 0.34 vs. 0.14). As compared with patients with stage F0 to F2 fibrosis, patients with stage F4 fibrosis also had a higher incidence of type 2 diabetes (7.53 vs. 4.45 events per 100 person-years) and a decrease of more than 40% in the estimated glomerular filtration rate (2.98 vs. 0.97 events per 100 person-years). The incidence of cardiac events and non-hepatic cancers were similar across fibrosis stages. After adjustment for age, sex, race, diabetes status, and baseline histologic severity, the incidence of any hepatic decompensation event (variceal hemorrhage, ascites, or encephalopathy) was associated with increased all-cause mortality (adjusted hazard ratio = 6.8; 95% confidence interval: 2.2–21.3).

Conclusions: In this prospective study involving patients with non-alcoholic fatty liver disease, fibrosis stages F3 and F4 were associated with increased risks of liver-related complications and death.

A.J. Sanyal, M.D., Professor of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, 1220 E. Broad Street, Richmond, VA 23298-0565, USA,

E-Mail: arun.sanyal@vcuhealth.org

J Hepatol. 2021;75(5):1026–33

Arab JP, Díaz LA, Baeza N, Idalsoaga F, Fuentes-López E, Arnold J, Ramírez CA, Morales-Arraez D, Ventura-Cots M, Alvarado-Tapias E, Zhang W, Clark V, Simonetto D, Ahn JC, Buryska S, Mehta TI, Stefanescu H, Horhat A, Bumbu A, Dunn W, Attar B, Agrawal R, Haque ZS, Majeed M, Cabezas J, García-Carrera I, Parker R, Cuyàs B, Poca M, Soriano G, Sarin SK, Maiwall R, Jalal PK, Abdulsada S, Higuera-de la Tijera MF, Kulkarni AV, Rao PN, Guerra Salazar P, Skladaný L, Bystrianska N, Prado V, Clemente-Sanchez A, Rincón D, Haider T, Chacko KR, Cairo F, de Sousa Coelho M, Romero GA, Pollarsky FD, Restrepo JC, Castro-Sanchez S, Toro LG, Yaquich P, Mendizabal M, Garrido ML, Narvaez A, Bessone F, Marcelo JS, Piombino D, Dirchwolf M, Arancibia JP, Altamirano J, Kim W, Araujo RC, Duarte Rojo A, Vargas V, Rautou PE, Issoufaly T, Zamarripa F, Torre A, Lucey MR, Mathurin P, Louvet A, García-Tsao G, González JA, Verna E, Brown RS, Roblero JP, Abraldes JG, Arrese M, Shah VH, Kamath PS, Singal AK, Bataller R

Identification of optimal therapeutic window for steroid use in severe alcohol-associated hepatitis: A worldwide study

Background and aims: Corticosteroids are the only effective therapy for severe alcohol-associated hepatitis (AH), defined by a model for end-stage liver disease (MELD) score > 20. However, there are patients who may be too sick to benefit from therapy. Herein, the authors aimed to identify the range of MELD scores within which steroids are effective for AH.
Methods: They performed a retrospective, international multicenter cohort study across 4 continents, including 3380 adults with a clinical and/or histological diagnosis of AH. The main outcome was mortality at 30 days. They used a discrete-time survival analysis model, and MELD cut-offs were established using the transform-the-end points method.
Results: In this cohort, median age was 49 (40–56) years, 76.5% were male, and 79% had underlying cirrhosis. Median MELD at admission was 24 (19–29). Survival was 88% (87–89) at 30 days, 77% (76–78) at 90 days, and 72% (72–74) at 180 days. A total of 1225 patients received corticosteroids. In an adjusted-survival-model, corticosteroid use decreased 30-day mortality by 41% (hazard ratio [HR] = 0.59; 95% confidence interval [CI]: 0.47–0.74; p < 0.001). Steroids only improved survival in patients with MELD scores between 21 (HR = 0.61; 95% CI: 0.39–0.95; p = 0.027) and 51 (HR = 0.72; 95% CI: 0.52–0.99; p = 0.041). The maximum effect of corticosteroid treatment (21–30% survival benefit) was observed with MELD scores between 25 (HR = 0.58; 95% CI: 0.42–0.77; p < 0.001) and 39 (HR = 0.57; 95% CI: 0.41–0.79; p < 0.001). No corticosteroid benefit was seen in patients with MELD > 51. The type of corticosteroids used (prednisone, prednisolone, or methylprednisolone) was not associated with survival benefit (p = 0.247).

Conclusion: Corticosteroids improve 30-day survival only among patients with severe alcohol-associated hepatitis, especially with MELD scores between 25 and 39.

Prof. Dr. J.P. Arab, Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, 8330024 Santiago, Chile,

E-Mail: jparab@uc.cl

Hepatology. 2021;74(5):2714–24

Otero Sanchez L, Karakike E, Njimi H, Putignano A, Degré D, Hites M, Jacobs F, Moreno C, Trepo E, Gustot T

Clinical course and risk factors for infection in severe forms of alcohol-associated liver disease

Background and aims: Infection is a major driver of mortality in patients with advanced alcohol-associated liver disease (ALD). The epidemiology and clinical course of patients infected with life-threatening forms of ALD, including severe alcohol-associated hepatitis (sAH) and decompensated alcohol-associated cirrhosis (DAC), and specific risk factors for infection remain mostly unknown.
Approach and results: In this observational study, the authors assessed all infectious episodes occurring within a 90-day period from diagnosis in all consecutive patients with biopsy-proven sAH (modified Maddrey's discriminant function ≥ 32, Model for End-Stage Liver Disease [MELD] ≥ 18) and DAC (MELD ≥ 18) without alcohol-associated hepatitis in this tertiary hospital between 2003 and 2016. A total of 207 patients were included: 139 with sAH and 68 with DAC. 117 patients (84%) with sAH and 41 patients (60%) with DAC experienced at least one infection episode at 90 days (p < 0.001). In multivariable analysis, factors associated with the development of infection were the presence of sAH and baseline MELD score. Bacterial infections represented the most common infection in the 2 groups, and only the MELD score was independently associated with the occurrence of bacterial infection. In both groups, pneumonia was the most prevalent bacterial infection, and gram-negative bacilli were the main pathogens. Invasive fungal infections (IFI) occurred in 20 patients (14.5%) with sAH and in 3 patients (4.5%) with DAC (p < 0.05). Multivariable regression showed that younger age, higher MELD, and corticosteroid therapy were independently associated with IFI. The 90-day cumulative incidence of death in patients infected with sAH and patients infected with DAC was 46% and 41.5%, respectively (p = 0.43).

Conclusions: Patients with severe alcohol-associated hepatitis (sAH) are more susceptible to develop infection than those with decompensated alcohol-associated cirrhosis. In life-threatening forms of alcohol-associated liver disease, patients who were infected share a similar mortality rate. Corticosteroid treatment, not sAH, seems to be the main risk factor triggering invasive fungal infections.

Dr. Dr. T. Gustot, Liver Transplant Unit or Dr. L. Otero Sanchez, Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, C.U.B. Erasme Hospital, Route de Lennik, 808, 1070 Brussels, Belgium,

E-Mail: thierry.gustot@erasme.ulb.ac.be

E-Mail: lukas.otero.sanchez@ulb.be

Gut. 2021;70(11):2066–75

Seo SI, Park CH, You SC, Kim JY, Lee KJ, Kim J, Kim Y, Yoo JJ, Seo WW, Lee HS, Shin WG

Association between proton-pump inhibitor use and gastric cancer: A population-based cohort study using 2 different types of nationwide databases in Korea

Objective: The association between proton-pump inhibitor (PPI) use and gastric cancer related to Helicobacter pylori eradication has not been fully investigated in geographical regions with high risk of gastric cancer. The aim of this study was to evaluate the association between PPIs and gastric cancer in Korea.
Design: This study analyzed the original and common data model versions of the Korean National Health Insurance Service database from 2002 to 2013. The authors compared the incidence rates of gastric cancer after 1-year drug exposure, between new users of PPIs and other drugs excluding PPIs, by Cox proportional hazards model. They also analyzed the incidence of gastric cancer among PPI users after H. pylori eradication.
Results: The analysis included 11,741 patients in matched PPI and non-PPI cohorts after large-scale propensity score matching. During a median follow-up of 4.3 years, PPI use was associated with a 2.37-fold increased incidence of gastric cancer (PPI ≥ 30 days vs. non-PPI; 118/51,813 person-years vs. 40/49,729 person-years; hazard ratio [HR] = 2.37, 95% confidence interval [CI]: 1.56–3.68, p = 0.001). The incidence rates of gastric cancer showed an increasing trend parallel to the duration of PPI use. In H. pylori-eradicated subjects, the incidence of gastric cancer was significantly associated with PPI use over 180 days compared with the non-PPI group (PPI ≥ 180 days vs. non-PPI; 30/12,470 person-years vs. 9/7814 person-years; HR = 2.22, 95% CI: 1.05–4.67, p = 0.036).

Conclusion: Proton-pump inhibitor (PPI) use was associated with gastric cancer, regardless of Helicobacter pylori eradication status. Long-term PPIs should be used with caution in high-risk regions for gastric cancer.

Prof. Dr. W.G. Shin, Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, South Korea,

E-Mail: sgun9139@gmail.com

Gut. 2021;70(11):2096–104

Merino J, Joshi AD, Nguyen LH, Leeming ER, Mazidi M, Drew DA, Gibson R, Graham MS, Lo CH, Capdevila J, Murray B, Hu C, Selvachandran S, Hammers A, Bhupathiraju SN, Sharma SV, Sudre C, Astley CM, Chavarro JE, Kwon S, Ma W, Menni C, Willett WC, Ourselin S, Steves CJ, Wolf J, Franks PW, Spector TD, Berry S, Chan AT

Diet quality and risk and severity of COVID-19: A prospective cohort study

Objective: Poor metabolic health and unhealthy lifestyle factors have been associated with risk and severity of COVID-19, but data for diet are lacking. The aim of this study was to investigate the association of diet quality with risk and severity of COVID-19 and its interaction with socioeconomic deprivation.
Design: Data from 592,571 participants of the smartphone-based COVID-19 Symptom Study were used. Diet information was collected for the prepandemic period using a short food frequency questionnaire, and diet quality was assessed using a healthful Plant-Based Diet Score, which emphasizes healthy plant foods such as fruits or vegetables. Multivariable Cox models were fitted to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for COVID-19 risk and severity defined using a validated symptom-based algorithm or hospitalization with oxygen support, respectively.
Results: Over 3,886,274 person-months of follow-up, 31,815 COVID-19 cases were documented. Compared with individuals in the lowest quartile of the diet score, high diet quality was associated with lower risk of COVID-19 (HR = 0.91; 95% CI: 0.88–0.94) and severe COVID-19 (HR = 0.59; 95% CI: 0.47–0.74). The joint association of low diet quality and increased deprivation on COVID-19 risk was higher than the sum of the risk associated with each factor alone (pinteraction = 0.005). The corresponding absolute excess rate per 10,000 person/months for lowest versus highest quartile of diet score was 22.5 (95% CI: 18.8–26.3) among persons living in areas with low deprivation and 40.8 (95% CI: 31.7–49.8) among persons living in areas with high deprivation.

Conclusions: A diet characterized by healthy plant-based foods was associated with lower risk and severity of COVID-19. This association may be particularly evident among individuals living in areas with higher socioeconomic deprivation.

A.T. Chan, M.D., Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA,

E-Mail: achan@mgh.harvard.edu

Clin Gastroenterol Hepatol. 2021;19(11):2315–23.e2

Jensen DM, Kovacs T, Ghassemi KA, Kaneshiro M, Gornbein J

Randomized controlled trial of over-the-scope clip as initial treatment of severe non-variceal upper gastrointestinal bleeding

Background and aims: No prior randomized controlled trial (RCT) has reported patient outcomes of large over-the-scope clip (OTSC) compared to standard hemostasis as initial endoscopic treatment of severe non-variceal upper gastrointestinal bleeding (NVUGIB). This was the study aim.
Methods: Patients with bleeding ulcers or Dieulafoy's lesions and major stigmata of recent hemorrhage – SRH (active spurting bleeding, visible vessel, or clot) – or lesser SRH (oozing bleeding or flat spots – with arterial blood flow by Doppler probe) were randomized to OTSC or standard endoscopic hemostasis (with hemoclips or multipolar electrocoagulation – MPEC). Patients and their healthcare providers were blinded to treatments and made all post-randomization management decisions. Ulcer patients received high dose intravenous infusions of proton-pump inhibitors (PPI) for 3 days, then 27 days of oral PPI. 30-day outcomes were prospectively recorded; data management was with SAS; and data analysis was by a statistician.
Results: 53 patients (25 OTSC, 28 Standard) were randomized, with similar baseline risk factors. However, there were significant differences in OTSC versus standard groups in rates of rebleeding (4% vs. 28.6%; p = 0.017; relative risk = 0.10, 95% confidence interval: 0.01–0.91; number needed to treat = 4); severe complications (0% vs. 14.3%); and post-randomization units of red cell transfusions (0.04 vs. 0.68). All rebleeds occurred in patients with major SRH and none with lesser SRH.

Conclusion: 1. Over-the-scope clip (OTSC) significantly reduced rates of rebleeding, severe complications, and post-randomization red cell transfusions. 2. Patients with major stigmata benefited significantly from hemostasis with OTSC, but those with lesser stigmata did not.

D.M. Jensen, M.D., CURE: Digestive Diseases Research Core Center, Building 115, Room 318, VA Greater Los Angeles Healthcare System, 11301 Wilshire Boulevard, Los Angeles, CA 90073-1003, USA,

E-Mail: djensen@mednet.ucla.edu

N Engl J Med. 2021;385(15):1372–81

Boxhoorn L, van Dijk SM, van Grinsven J, Verdonk RC, Boermeester MA, Bollen TL, Bouwense SAW, Bruno MJ, Cappendijk VC, Dejong CHC, van Duijvendijk P, van Eijck CHJ, Fockens P, Francken MFG, van Goor H, Hadithi M, Hallensleben NDL, Haveman JW, Jacobs MAJM, Jansen JM, Kop MPM, van Lienden KP, Manusama ER, Mieog JSD, Molenaar IQ, Nieuwenhuijs VB, Poen AC, Poley JW, van de Poll M, Quispel R, Römkens TEH, Schwartz MP, Seerden TC, Stommel MWJ, Straathof JWA, Timmerhuis HC, Venneman NG, Voermans RP, van de Vrie W, Witteman BJ, Dijkgraaf MGW, van Santvoort HC, Besselink MG; Dutch Pancreatitis Study Group

Immediate versus postponed intervention for infected necrotizing pancreatitis

Background: Infected necrotizing pancreatitis is a potentially lethal disease that is treated with the use of a step-up approach, with catheter drainage often delayed until the infected necrosis is encapsulated. Whether outcomes could be improved by earlier catheter drainage is unknown.
Methods: The autors conducted a multicenter, randomized superiority trial involving patients with infected necrotizing pancreatitis, in which they compared immediate drainage within 24 hours after randomization once infected necrosis was diagnosed with drainage that was postponed until the stage of walled-off necrosis was reached. The primary end point was the score on the Comprehensive Complication Index, which incorporates all complications over the course of 6 months of follow-up.
Results: A total of 104 patients were randomly assigned to immediate drainage (55 patients) or postponed drainage (49 patients). The mean score on the Comprehensive Complication Index (scores range from 0 to 100, with higher scores indicating more severe complications) was 57 in the immediate-drainage group and 58 in the postponed-drainage group (mean difference, -1; 95% confidence interval [CI]: -12–10; p = 0.90). Mortality was 13% in the immediate-drainage group and 10% in the postponed-drainage group (relative risk = 1.25; 95% CI: 0.42–3.68). The mean number of interventions (catheter drainage and necrosectomy) was 4.4 in the immediate-drainage group and 2.6 in the postponed-drainage group (mean difference, 1.8; 95% CI: 0.6–3.0). In the postponed-drainage group, 19 patients (39%) were treated conservatively with antibiotics and did not require drainage; 17 of these patients survived. The incidence of adverse events was similar in the 2 groups.

Conclusions: This trial did not show the superiority of immediate drainage over postponed drainage with regard to complications in patients with infected necrotizing pancreatitis. Patients randomly assigned to the postponed-drainage strategy received fewer invasive interventions.

Prof. Dr. M.G. Besselink, Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands,

E-Mail: m.g.besselink@amsterdamumc.nl