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  • Comparison of lumen-apposing metal stents versus double-pigtail plastic stents for infected necrotising pancreatitis GUT Boxhoorn, L., Verdonk, R. C., Besselink, M. G., Boermeester, M., Bollen, T. L., Bouwense, S. W., Cappendijk, V. C., Curvers, W. L., Dejong, C. H., van Dijk, S. M., van Dullemen, H. M., van Eijck, C. J., van Geenen, E. M., Hadithi, M., Hazen, W. L., Honkoop, P., van Hooft, J. E., Jacobs, M. M., Kievits, J. C., Kop, M. M., Kouw, E., Kuiken, S. D., Ledeboer, M., Nieuwenhuijs, V. B., Perk, L. E., Poley, J., Quispel, R., de Ridder, R. J., van Santvoort, H. C., Sperna Weiland, C. J., Stommel, M. J., Timmerhuis, H. C., Witteman, B. J., Umans, D. S., Venneman, N. G., Vleggaar, F. P., van Wanrooij, R. J., Bruno, M. J., Fockens, P., Voermans, R. P. 2022


    Lumen-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.Patients 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.A 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).Our 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.

    View details for DOI 10.1136/gutjnl-2021-325632

    View details for Web of Science ID 000811674900001

    View details for PubMedID 35701094

  • Performance of diagnostic tools for acute cholangitis in patients with suspected biliary obstruction JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES Weiland, C., Busch, C. E., Bhalla, A., Bruno, M. J., Fockens, P., van Hooft, J. E., Poen, A. C., Timmerhuis, H. C., Umans, D. S., Venneman, N. G., Verdonk, R. C., Drenth, J. H., de Wijkerslooth, T. R., van Geenen, E. M., Dutch Pancreatitis Study Grp 2022; 29 (4): 479-486


    Acute cholangitis is an infection requiring endoscopic retrograde cholangiopancreatography (ERCP) and antibiotics. Several diagnostic tools help to diagnose cholangitis. Because diagnostic performance of these tools has not been studied and might therefore impose unnecessary ERCPs, we aimed to evaluate this.We established a nationwide prospective cohort of patients with suspected biliary obstruction who underwent an ERCP. We assessed the diagnostic performance of Tokyo Guidelines (TG18), Dutch Pancreatitis Study Group (DPSG) criteria, and Charcot triad relative to real-world cholangitis as the reference standard.127 (16%) of 794 patients were diagnosed with real-world cholangitis. Using the TG18, DPSG, and Charcot triad, 345 (44%), 55 (7%), and 66 (8%) patients were defined as having cholangitis, respectively. Sensitivity for TG18 was 82% (95% CI 74-88) and specificity 60% (95% CI 56-63). The sensitivity for DPSG and Charcot was 42% (95% CI 33-51) and 46% (95% CI 38-56), specificity was 99.7% (95% CI 99-100) and 99% (95% CI 98-100), respectively.TG18 criteria incorrectly diagnoses four out of ten patients with real-world cholangitis, while DPSG and Charcot criteria failed to diagnose more than half of patients. As the cholangitis diagnosis has many consequences for treatment, there is a need for more accurate diagnostic tools or work-up towards ERCP.

    View details for DOI 10.1002/jhbp.1096

    View details for Web of Science ID 000731983000001

    View details for PubMedID 34932265

  • Immediate versus Postponed Intervention for Infected Necrotizing Pancreatitis. The New England journal of medicine Boxhoorn, L., van Dijk, S. M., van Grinsven, J., Verdonk, R. C., Boermeester, M. A., Bollen, T. L., Bouwense, S. A., Bruno, M. J., Cappendijk, V. C., Dejong, C. H., van Duijvendijk, P., van Eijck, C. H., Fockens, P., Francken, M. F., van Goor, H., Hadithi, M., Hallensleben, N. D., Haveman, J. W., Jacobs, M. A., Jansen, J. M., Kop, M. P., van Lienden, K. P., Manusama, E. R., Mieog, J. S., Molenaar, I. Q., Nieuwenhuijs, V. B., Poen, A. C., Poley, J. W., van de Poll, M., Quispel, R., Römkens, T. E., Schwartz, M. P., Seerden, T. C., Stommel, M. W., Straathof, J. W., Timmerhuis, H. C., Venneman, N. G., Voermans, R. P., van de Vrie, W., Witteman, B. J., Dijkgraaf, M. G., van Santvoort, H. C., Besselink, M. G. 2021; 385 (15): 1372-1381


    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.We conducted a multicenter, randomized superiority trial involving patients with infected necrotizing pancreatitis, in which we 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.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 to 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 to 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 to 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 two groups.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. (Funded by Fonds NutsOhra and Amsterdam UMC; POINTER ISRCTN Registry number, ISRCTN33682933.).

    View details for DOI 10.1056/NEJMoa2100826

    View details for PubMedID 34614330

  • Diagnosis and treatment of pancreatic duct disruption or disconnection: an international expert survey and case vignette study. HPB : the official journal of the International Hepato Pancreato Biliary Association Boxhoorn, L., Timmerhuis, H. C., Verdonk, R. C., Besselink, M. G., Bollen, T. L., Bruno, M. J., Elmunzer, B. J., Fockens, P., Horvath, K. D., van Santvoort, H. C., Voermans, R. P. 2021; 23 (8): 1201-1208


    Pancreatic duct disruption or disconnection is a potentially severe complication of necrotizing pancreatitis. With no existing treatment guidelines, it is unclear whether there is any consensus among experts in clinical practice. We evaluated current expert opinion regarding the diagnosis and treatment of pancreatic duct disruption and disconnection in an international case vignette study.An online case vignette survey was sent to 110 international expert pancreatologists. Expert selection was based on publications in the last 5 years and/or participation in development of IAP/APA and ESGE guidelines on acute pancreatitis. Consensus was defined as agreement by at least 75% of the experts.The response rate was 51% (n = 56). Forty-four experts (79%) obtained a MRI/MRCP and 52 experts (93%) measured amylase levels in percutaneous drain fluid to evaluate pancreatic duct integrity. The majority of experts favored endoscopic transluminal drainage for infected (peri)pancreatic necrosis and pancreatic duct disruption (84%, n = 45) or disconnection (88%, n = 43). Consensus was lacking regarding the treatment of patients with persistent percutaneous drain production, and with persistent sterile necrosis.This international survey of experts demonstrates that there are many areas for which no consensus existed, providing clear focus for future investigation.

    View details for DOI 10.1016/j.hpb.2020.11.1148

    View details for PubMedID 33541807

  • Aggressive fluid hydration plus non-steroidal anti-inflammatory drugs versus non-steroidal anti-inflammatory drugs alone for post-endoscopic retrograde cholangiopancreatography pancreatitis (FLUYT): a multicentre, open-label, randomised, controlled trial. The lancet. Gastroenterology & hepatology Sperna Weiland, C. J., Smeets, X. J., Kievit, W., Verdonk, R. C., Poen, A. C., Bhalla, A., Venneman, N. G., Witteman, B. J., da Costa, D. W., van Eijck, B. C., Schwartz, M. P., Römkens, T. E., Vrolijk, J. M., Hadithi, M., Voorburg, A. M., Baak, L. C., Thijs, W. J., van Wanrooij, R. L., Tan, A. C., Seerden, T. C., Keulemans, Y. C., de Wijkerslooth, T. R., van de Vrie, W., van der Schaar, P., van Dijk, S. M., Hallensleben, N. D., Sperna Weiland, R. L., Timmerhuis, H. C., Umans, D. S., van Hooft, J. E., van Goor, H., van Santvoort, H. C., Besselink, M. G., Bruno, M. J., Fockens, P., Drenth, J. P., van Geenen, E. J. 2021; 6 (5): 350-358


    Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Prophylactic rectal administration of non-steroidal anti-inflammatory drugs (NSAIDs) is considered as standard of care to reduce the risk of post-ERCP pancreatitis. It has been suggested that aggressive hydration might further reduce this risk. Guidelines already recommend aggressive hydration in patients who are unable to receive rectal NSAIDs, although it is laborious and time consuming. We aimed to evaluate the added value of aggressive hydration in patients receiving prophylactic rectal NSAIDs.FLUYT, a multicentre, open-label, randomised, controlled trial done across 22 Dutch hospitals, included patients aged between 18 and 85 years with moderate to high risk of post-ERCP pancreatitis. Patients were randomly assigned (1:1) by a web-based module with varying block sizes to a combination of aggressive hydration and rectal NSAIDs (100 mg diclofenac or indomethacin; aggressive hydration group) or rectal NSAIDs (100 mg diclofenac or indomethacin) alone (control group). Randomisation was stratified according to treatment centre. Aggressive hydration comprised 20 mL/kg intravenous Ringer's lactate solution within 60 min from the start of ERCP, followed by 3 mL/kg per h for 8 h. The control group received normal intravenous saline with a maximum of 1·5 mL/kg per h and 3 L per 24 h. The primary endpoint was post-ERCP pancreatitis and was analysed on a modified intention-to-treat basis (including all patients who underwent randomisation and an ERCP and for whom data regarding the primary outcome were available). The trial is registered with the ISRCTN registry, ISRCTN13659155.Between June 5, 2015, and June 6, 2019, 826 patients were randomly assigned, of whom 388 in the aggressive hydration group and 425 in the control group were included in the modified intention-to-treat analysis. Post-ERCP pancreatitis occurred in 30 (8%) patients in the aggressive hydration group and in 39 (9%) patients in the control group (relative risk 0·84, 95% CI 0·53-1·33, p=0·53). There were no differences in serious adverse events, including hydration-related complications (relative risk 0·99, 95% CI 0·59-1·64; p=1·00), ERCP-related complications (0·90, 0·62-1·31; p=0·62), intensive care unit admission (0·37, 0·07-1·80; p=0·22), and 30-day mortality (0·95, 0·50-1·83; p=1·00).Aggressive periprocedural hydration did not reduce the incidence of post-ERCP pancreatitis in patients with moderate to high risk of developing this complication who routinely received prophylactic rectal NSAIDs. Therefore, the burden of laborious and time-consuming aggressive periprocedural hydration to further reduce the risk of post-ERCP pancreatitis is not justified.Netherlands Organisation for Health Research and Development and Radboud University Medical Center.

    View details for DOI 10.1016/S2468-1253(21)00057-1

    View details for PubMedID 33740415

  • Various Modalities Accurate in Diagnosing a Disrupted or Disconnected Pancreatic Duct in Acute Pancreatitis: A Systematic Review. Digestive diseases and sciences Timmerhuis, H. C., van Dijk, S. M., Verdonk, R. C., Bollen, T. L., Bruno, M. J., Fockens, P., van Hooft, J. E., Voermans, R. P., Besselink, M. G., van Santvoort, H. C. 2021; 66 (5): 1415-1424


    Severe pancreatitis may result in a disrupted pancreatic duct, which is associated with a complicated clinical course. Diagnosis of a disrupted pancreatic duct is not standardized in clinical practice or international guidelines. We performed a systematic review of the literature on imaging modalities for diagnosing a disrupted pancreatic duct in patients with acute pancreatitis.A systematic search was performed in PubMed, Embase and Cochrane library databases to identify all studies evaluating diagnostic modalities for the diagnosis of a disrupted pancreatic duct in acute pancreatitis. All data regarding diagnostic accuracy were extracted.We included 8 studies, evaluating five different diagnostic modalities in 142 patients with severe acute pancreatitis. Study quality was assessed, with proportionally divided high and low risk of bias and low applicability concerns in 75% of the studies. A sensitivity of 100% was reported for endoscopic ultrasound and endoscopic retrograde cholangiopancreatography. The sensitivity of magnetic resonance cholangiopancreatography with or without secretin was 83%. A sensitivity of 92% was demonstrated for a combined cohort of secretin-magnetic resonance cholangiopancreatography and magnetic resonance cholangiopancreatography. A sensitivity of 100% and specificity of 50% was found for amylase measurements in drain fluid compared with ERCP.This review suggests that various diagnostic modalities are accurate in diagnosing a disrupted pancreatic duct in patients with acute pancreatitis. Amylase measurement in drain fluid should be standardized. Given the invasive nature of other modalities, secretin-magnetic resonance cholangiopancreatography or magnetic resonance cholangiopancreatography would be recommended as first diagnostic modality. Further prospective studies, however, are needed.

    View details for DOI 10.1007/s10620-020-06413-0

    View details for PubMedID 32594462

    View details for PubMedCentralID PMC8053185

  • Optimal timing of cholecystectomy after necrotising biliary pancreatitis. Gut Hallensleben, N. D., Timmerhuis, H. C., Hollemans, R. A., Pocornie, S., van Grinsven, J., van Brunschot, S., Bakker, O. J., van der Sluijs, R., Schwartz, M. P., van Duijvendijk, P., Römkens, T., Stommel, M. W., Verdonk, R. C., Besselink, M. G., Bouwense, S. A., Bollen, T. L., van Santvoort, H. C., Bruno, M. J. 2021


    Following an episode of acute biliary pancreatitis, cholecystectomy is advised to prevent recurrent biliary events. There is limited evidence regarding the optimal timing and safety of cholecystectomy in patients with necrotising biliary pancreatitis.A post hoc analysis of a multicentre prospective cohort. Patients with biliary pancreatitis and a CT severity score of three or more were included in 27 Dutch hospitals between 2005 and 2014. Primary outcome was the optimal timing of cholecystectomy in patients with necrotising biliary pancreatitis, defined as: the optimal point in time with the lowest risk of recurrent biliary events and the lowest risk of complications of cholecystectomy. Secondary outcomes were the number of recurrent biliary events, periprocedural complications of cholecystectomy and the protective value of endoscopic sphincterotomy for the recurrence of biliary events.Overall, 248 patients were included in the analysis. Cholecystectomy was performed in 191 patients (77%) at a median of 103 days (P25-P75: 46-222) after discharge. Infected necrosis after cholecystectomy occurred in four (2%) patients with persistent peripancreatic collections. Before cholecystectomy, 66 patients (27%) developed biliary events. The risk of overall recurrent biliary events prior to cholecystectomy was significantly lower before 10 weeks after discharge (risk ratio 0.49 (95% CI 0.27 to 0.90); p=0.02). The risk of recurrent pancreatitis before cholecystectomy was significantly lower before 8 weeks after discharge (risk ratio 0.14 (95% CI 0.02 to 1.0); p=0.02). The complication rate of cholecystectomy did not decrease over time. Endoscopic sphincterotomy did not reduce the risk of recurrent biliary events (OR 1.40 (95% CI 0.74 to 2.83)).The optimal timing of cholecystectomy after necrotising biliary pancreatitis, in the absence of peripancreatic collections, is within 8 weeks after discharge.

    View details for DOI 10.1136/gutjnl-2021-324239

    View details for PubMedID 34272261

  • Endoscopic ultrasonography can detect a cause in the majority of patients with idiopathic acute pancreatitis: a systematic review and meta-analysis. Endoscopy Umans, D. S., Rangkuti, C. K., Sperna Weiland, C. J., Timmerhuis, H. C., Bouwense, S. A., Fockens, P., Besselink, M. G., Verdonk, R. C., van Hooft, J. E. 2020; 52 (11): 955-964


    Idiopathic acute pancreatitis (IAP) has a 25 % pancreatitis recurrence rate. Endoscopic ultrasonography (EUS) may diagnose treatable causes of IAP and hence prevent recurrence. The goal of this systematic review with meta-analysis is to determine the diagnostic yield of EUS and its impact on recurrence.PubMed, EMBASE and the Cochrane Library were systematically searched for English studies on EUS in adults with IAP. The primary outcome was diagnostic yield. Secondary outcomes included recurrence. Methodological quality was assessed using the QUADAS-2 score. Meta-analysis was performed to calculate the pooled diagnostic yield and risk ratio with 95 % confidence intervals (CI) using a random-effects model with inverse variance method.22 studies were included, with 1490 IAP patients who underwent EUS. Overall diagnostic yield was 59 % (874 /1490; 95 %CI 52 % - 66 %). The most common etiologies were biliary (429 /1490; 30 %, 95 %CI 21 % - 41 %) and chronic pancreatitis (271 /1490; 12 %, 95 %CI 8 % - 19 %). In 2 % of patients, neoplasms were detected (45 /1490; 95 %CI 1 % - 4 %). There was no difference in yield between patients with or without recurrent IAP before EUS (risk ratio 0.89, 95 %CI 0.71 - 1.11).EUS is able to identify a potential etiology in the majority of patients with IAP, detecting mostly biliary origin or chronic pancreatitis, but also neoplasms in 2 % of patients. EUS may be associated with a reduction of recurrence rate. Future studies should include complete diagnostic work-up and preferably include patients with a first episode of IAP only.

    View details for DOI 10.1055/a-1183-3370

    View details for PubMedID 32557477

  • Role of endoscopic ultrasonography in the diagnostic work-up of idiopathic acute pancreatitis (PICUS): study protocol for a nationwide prospective cohort study. BMJ open Umans, D. S., Timmerhuis, H. C., Hallensleben, N. D., Bouwense, S. A., Anten, M. G., Bhalla, A., Bijlsma, R. A., Boermeester, M. A., Brink, M. A., Hol, L., Bruno, M. J., Curvers, W. L., van Dullemen, H. M., van Eijck, B. C., Erkelens, G. W., Fockens, P., van Geenen, E. J., Hazen, W. L., Hoge, C. V., Inderson, A., Kager, L. M., Kuiken, S. D., Perk, L. E., Poley, J. W., Quispel, R., Römkens, T. E., van Santvoort, H. C., Tan, A. C., Thijssen, A. Y., Venneman, N. G., Vleggaar, F. P., Voorburg, A. M., van Wanrooij, R. L., Witteman, B. J., Verdonk, R. C., Besselink, M. G., van Hooft, J. E. 2020; 10 (8): e035504


    Idiopathic acute pancreatitis (IAP) remains a dilemma for physicians as it is uncertain whether patients with IAP may actually have an occult aetiology. It is unclear to what extent additional diagnostic modalities such as endoscopic ultrasonography (EUS) are warranted after a first episode of IAP in order to uncover this aetiology. Failure to timely determine treatable aetiologies delays appropriate treatment and might subsequently cause recurrence of acute pancreatitis. Therefore, the aim of the Pancreatitis of Idiopathic origin: Clinical added value of endoscopic UltraSonography (PICUS) Study is to determine the value of routine EUS in determining the aetiology of pancreatitis in patients with a first episode of IAP.PICUS is designed as a multicentre prospective cohort study of 106 patients with a first episode of IAP after complete standard diagnostic work-up, in whom a diagnostic EUS will be performed. Standard diagnostic work-up will include a complete personal and family history, laboratory tests including serum alanine aminotransferase, calcium and triglyceride levels and imaging by transabdominal ultrasound, magnetic resonance imaging or magnetic resonance cholangiopancreaticography after clinical recovery from the acute pancreatitis episode. The primary outcome measure is detection of aetiology by EUS. Secondary outcome measures include pancreatitis recurrence rate, severity of recurrent pancreatitis, readmission, additional interventions, complications, length of hospital stay, quality of life, mortality and costs, during a follow-up period of 12 months.PICUS is conducted according to the Declaration of Helsinki and Guideline for Good Clinical Practice. Five medical ethics review committees assessed PICUS (Medical Ethics Review Committee of Academic Medical Center, University Medical Center Utrecht, Radboud University Medical Center, Erasmus Medical Center and Maastricht University Medical Center). The results will be submitted for publication in an international peer-reviewed journal.Netherlands Trial Registry (NL7066). Prospectively registered.

    View details for DOI 10.1136/bmjopen-2019-035504

    View details for PubMedID 32819938

    View details for PubMedCentralID PMC7440829

  • Treatment of disrupted and disconnected pancreatic duct in necrotizing pancreatitis: A systematic review and meta-analysis. Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] van Dijk, S. M., Timmerhuis, H. C., Verdonk, R. C., Reijnders, E., Bruno, M. J., Fockens, P., Voermans, R. P., Besselink, M. G., van Santvoort, H. C. 2019; 19 (7): 905-915


    Necrotizing pancreatitis may lead to loss of integrity of the pancreatic duct, resulting in leakage of pancreatic fluid. Pancreatic duct disruption or disconnection is associated with a prolonged disease course and particular complications. Since a standard treatment for this condition is currently lacking, we performed a systematic review of the literature to compare outcomes of various treatment strategies.A systematic review was performed according to the PRISMA guidelines in the PubMed, EMBASE and Cochrane databases. Included were articles considering the treatment of patients with disrupted or disconnected pancreatic duct resulting from acute necrotizing pancreatitis.Overall, 21 observational cohort studies were included comprising a total of 583 relevant patients. The most frequently used treatment strategies included endoscopic transpapillary drainage, endoscopic transluminal drainage, surgical drainage or resection, or combined procedures. Pooled analysis showed success rates of 81% (95%-CI: 60-92%) for transpapillary and 92% (95%-CI: 77-98%) for transluminal drainage, 80% (95%-CI: 67-89%) for distal pancreatectomy and 84% (95%-CI: 73-91%) for cyst-jejunostomy. Success rates did not differ between surgical procedures (cyst-jejunostomy and distal pancreatectomy (risk ratio = 1.06, p = .26)) but distal pancreatectomy was associated with a higher incidence of endocrine pancreatic insufficiency (risk ratio = 3.06, p = .01). The success rate of conservative treatment is unknown.Different treatment strategies for pancreatic duct disruption and duct disconnection after necrotizing pancreatitis show high success rates but various sources of bias in the available studies are likely. High-quality prospective, studies, including unselected patients, are needed to establish the most effective treatment in specific subgroups of patients, including timing of treatment and long-term follow-up.

    View details for DOI 10.1016/j.pan.2019.08.006

    View details for PubMedID 31473083