Dutch Pancreatitis Study Group Research Articles

Long-Term Outcomes of Early Surgery vs Endoscopy First in Chronic Pancreatitis

Patients with painful chronic pancreatitis and a dilated pancreatic duct can be treated by early surgery or an endoscopy-first approach. To compare long-term clinical outcomes of early surgery vs an endoscopy-first approach using follow-up data from the ESCAPE randomized clinical trial. 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. Patients with chronic pancreatitis were randomly assigned to early surgery or an endoscopy-first approach. 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. 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]). 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.

Preventing recurrent ‘Idiopathic’ acute pancreatitis through laparoscopic cholecystectomy (PICUS-2): protocol for a multicenter randomized trial: Dutch Pancreatitis Study Group

Preventing recurrent ‘Idiopathic’ acute pancreatitis through laparoscopic cholecystectomy (PICUS-2): protocol for a multicenter randomized trial: Dutch Pancreatitis Study Group

Early Omega-3-fatty acid infusion for reduction of organ failure and mortality in predicted severe acute pancreatitis: protocol for a multicenter randomized controlled trial (PLANCTON) by the Dutch Pancreatitis Study Group

Early Omega-3-fatty acid infusion for reduction of organ failure and mortality in predicted severe acute pancreatitis: protocol for a multicenter randomized controlled trial (PLANCTON) by the Dutch Pancreatitis Study Group

Therapeutic anticoagulation for splanchnic vein thrombosis in acute pancreatitis: A national survey and case-vignette study.

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. To gain insight into current opinions and clinical decision making of pancreatologists regarding SVT in acute pancreatitis. 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%. 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. 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.

High risk of complications and mortality in cirrhotic patients with acute pancreatitis

High risk of complications and mortality in cirrhotic patients with acute pancreatitis

Performance of diagnostic tools for acute cholangitis in patients with suspected biliary obstruction.

BackgroundAcute 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.MethodsWe 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.Results127 (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.ConclusionsTG18 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.

Применение озоно-кислородной смеси у больных острым билиарным панкреатитом с желчной гипертензией

Цель: усовершенствовать хирургическое лечение больных острым билиарным панкреатитом с желчной гипертензией путем применения индивидуального подхода к выбору декомпрессионной технологии в ранней фазе заболевания и ранней профилактики инфекционных осложнений с использованием озоно-кислородной смеси. Материалы и методы. В исследование были привлечены 70 пациентов (22 мужчины и 48 женщин) с острым билиарным панкреатитом и желчной гипертензией разных возрастных групп (средний возраст — 57,2 года). У всех пациентов билиарное происхождение панкреатита диагностировано в соответствии с критериями, предложенными Голландской исследовательской группой по изучению панкреатита. Во всех случаях применен усовершенствованный алгоритм хирургического лечения, который предусматривал индивидуальный подход к выбору декомпрессионной технологии в первые 72 ч после первичного приступа абдоминальной боли независимо от срока госпитализации в клинику. Больных распределили на две группы. В первой группе (n = 32) после устранения билиарной гипертензии проводили профилактику инфекционных осложнений путем эндобилиарного введения озоно-кислородной смеси, растворенной в 0,9 NaCl, с концентрацией озона 2–4 мкг/мл, во второй группе (n = 38) профилактику не применяли. Для выявления возможного повреждающего действия озоно-кислородной смеси на желчный проток нами исследован пузырный проток у 12 больных острым билиарным панкреатитом с желчной гипертензией, у которых удалили желчный пузырь в острый период заболевания. Результаты. Проведены 49 фибро­гастродуоденоскопий с эндоскопической папиллосфинктеротомией и лито­экстракцией, 10 перкутанных чреспеченочных пункционных дренирований, 13 лапароскопических холецистэктомий с внешним дренированием внепеченочных желчных протоков (у 5 пациентов выполнена лапароскопическая холедохоскопия с литоэкстракцией). Некротические формы острого панкреатита развились у 11 (34,37 %) пациентов первой группы, из них у 5 (45,45 %) произошло инфицирование. Средняя длительность лечения составила 14,5 суток, летальность — 6,25 %. Во второй группе некротические формы острого панкреатита развились у 15 (39,47 %) пациентов, из них у 7 (46,6 %) произошло инфицирование. Средняя длительность лечения составила 16,46 суток, летальность — 10,5 %. Выводы. Применение ранней профилактики инфекционных осложнений у больных острым билиарным панкреатитом с желчной гипертензией в сочетании с выполнением декомпрессионных оперативных вмешательств для ликвидации желчной гипертензии в первые 72 ч от начала заболевания позволяет уменьшить частоту развития некротических и инфицированных форм, тяжесть заболевания, уровень летальности и длительность пребывания в стационаре, in vitro не вызывает альтеративных, дистрофических или дегенеративных изменений как на клеточном, так и на тканевом уровне во всех структурах стенки ductus cysticus.

Alcohol Reduction to Reduce Relapse in Acute Alcoholic Pancreatitis-Missed Opportunities.

AimResuming drinking is a main contributant to recurrence in alcoholic pancreatitis. We assessed current clinical practice in the Netherlands regarding alcohol in managing patients with a first episode of acute alcoholic pancreatitis.MethodsA survey was distributed to 35 hospitals affiliated with the Dutch Pancreatitis Study Group. We evaluated current support based on various components of brief interventions, the participation of psychosocial healthcare providers, the cooperation with the primary care physicians and the presence of a protocol and its implementation.ResultsThe response rate was 100% (n = 35). Psychoeducation is the most frequently performed intervention in current support treatment (97% of hospitals). In 17% of hospitals, healthcare providers with a psychosocial background routinely participate in current support treatment; 37% of hospitals create an individual treatment plan in which goals regarding alcohol cessation are specified and only 46% of hospitals provide the primary care physician with specific discharge information; 31% of hospitals indicate that the treatment is uniformly performed within their division of Gastroenterology. Protocols are available in 3% of the hospitals surveyed. Opportunities to involve the patient’s social network were not given sufficient priority.ConclusionAmong Dutch hospitals, there is no routine management strategy with regard to enhancing treatment for heavy alcohol use in alcoholic pancreatitis patients. There is a need to test a validated support program in randomized studies. Meanwhile, possible opportunities for effecting change are often missed.

Establishing and Coordinating a Nationwide Multidisciplinary Study Group: Lessons Learned by the Dutch Pancreatic Cancer Group.

Establishing and Coordinating a Nationwide Multidisciplinary Study Group: Lessons Learned by the Dutch Pancreatic Cancer Group.

Effect of Early Surgery vs Endoscopy-First Approach on Pain in Patients With Chronic Pancreatitis

For patients with painful chronic pancreatitis, surgical treatment is postponed until medical and endoscopic treatment have failed. Observational studies have suggested that earlier surgery could mitigate disease progression, providing better pain control and preserving pancreatic function. To determine whether early surgery is more effective than the endoscopy-first approach in terms of clinical outcomes. The ESCAPE trial was an unblinded, multicenter, randomized clinical superiority trial involving 30 Dutch hospitals participating in the Dutch Pancreatitis Study Group. From April 2011 until September 2016, a total of 88 patients with chronic pancreatitis, a dilated main pancreatic duct, and who only recently started using prescribed opioids for severe pain (strong opioids for ≤2 months or weak opioids for ≤6 months) were included. The 18-month follow-up period ended in March 2018. There were 44 patients randomized to the early surgery group who underwent pancreatic drainage surgery within 6 weeks after randomization and 44 patients randomized to the endoscopy-first approach group who underwent medical treatment, endoscopy including lithotripsy if needed, and surgery if needed. The primary outcome was pain, measured on the Izbicki pain score and integrated over 18 months (range, 0-100 [increasing score indicates more pain severity]). Secondary outcomes were pain relief at the end of follow-up; number of interventions, complications, hospital admissions; pancreatic function; quality of life (measured on the 36-Item Short Form Health Survey [SF-36]); and mortality. Among 88 patients who were randomized (mean age, 52 years; 21 (24%) women), 85 (97%) completed the trial. During 18 months of follow-up, patients in the early surgery group had a lower Izbicki pain score than patients in the group randomized to receive the endoscopy-first approach group (37 vs 49; between-group difference, -12 points [95% CI, -22 to -2]; P = .02). Complete or partial pain relief at end of follow-up was achieved in 23 of 40 patients (58%) in the early surgery vs 16 of 41 (39%)in the endoscopy-first approach group (P = .10). The total number of interventions was lower in the early surgery group (median, 1 vs 3; P < .001). Treatment complications (27% vs 25%), mortality (0% vs 0%), hospital admissions, pancreatic function, and quality of life were not significantly different between early surgery and the endoscopy-first approach. Among patients with chronic pancreatitis, early surgery compared with an endoscopy-first approach resulted in lower pain scores when integrated over 18 months. However, further research is needed to assess persistence of differences over time and to replicate the study findings. ISRCTN Identifier: ISRCTN45877994.

Serial endoscopic debridement via the VARD entrance as new treatment approach for necrotizing pancreatitis

Introduction: Necrotizing pancreatitis develops in approx. 15% of all patients with acute pancreatitis leading to mortality rates of up to 20%. Today, the gold standard of therapy is the so called step-up-approach. First, necrosis is drained by a CT-drainage and only if unsuccessful, therapy is being escalated towards endoscopic or surgically minimal invasive (VARD, video assisted retroperitoneal debridement) necrosectomy. The Tension trial of the Dutch Pancreatitis Study group demonstrated that both therapies are of equal use. We describe our experiences with a serial endoscopic debridement following VARD, thereby combining both techniques. Material and Methods: All patients who received serial endoscopic debridement following VARD at the Aachen University Hospital between 2016 and 2018 were included. After providing a sufficient drainage channel by VARD, endoscopic necrosectomies were performed on regular basis through this channel. This can be done in analgosedation, intubation anesthesia is not necessary. Results were compared with a VARD only cohort already described by us. Results: 8 patients (6 male, 2 female) received a VARD followed by serial endoscopic debridement. The average age was 51.8 ± 14.1 years, average BMI was 28.8 ± 7.1 and average ASA Score was 3.3 ± 0.5. In all patients, bacteria could be identified as sign of a superinfected necrosis. Endoscopic debridement took place 5 times (mean, [2-15]) in a time frame of 17 days (mean, [5-88] days). The 30-day-mortality was 0%. The time in the ICU was reduced significantly from 29 ± 41 days to 17 ± 23 days compared with VARD alone. The average postoperative stay was 68 ± 30 days. Conclusion: Serial endoscopic debridement via the VARD entrance is a further step of escalation in treating necrotizing pancreatitis. It seems to hold the advantage of combining both minimal invasive necrosectomy forms, endoscopic and VARD. Future prospective studies must investigate this advantage further.

The Dutch Pancreas Biobank Within the Parelsnoer Institute: A Nationwide Biobank of Pancreatic and Periampullary Diseases.

Large biobanks with uniform collection of biomaterials and associated clinical data are essential for translational research. The Netherlands has traditionally been well organized in multicenter clinical research on pancreatic diseases, including the nationwide multidisciplinary Dutch Pancreatic Cancer Group and Dutch Pancreatitis Study Group. To enable high-quality translational research on pancreatic and periampullary diseases, these groups established the Dutch Pancreas Biobank. The Dutch Pancreas Biobank is part of the Parelsnoer Institute and involves all 8 Dutch university medical centers and 5 nonacademic hospitals. Adult patients undergoing pancreatic surgery (all indications) are eligible for inclusion. Preoperative blood samples, tumor tissue from resected specimens, pancreatic cyst fluid, and follow-up blood samples are collected. Clinical parameters are collected in conjunction with the mandatory Dutch Pancreatic Cancer Audit. Between January 2015 and May 2017, 488 patients were included in the first 5 participating centers: 4 university medical centers and 1 nonacademic hospital. Over 2500 samples were collected: 1308 preoperative blood samples, 864 tissue samples, and 366 follow-up blood samples. Prospective collection of biomaterials and associated clinical data has started in the Dutch Pancreas Biobank. Subsequent translational research will aim to improve treatment decisions based on disease characteristics.

Admission Hematocrit and Rise in Blood Urea Nitrogen at 24 h Outperform other Laboratory Markers in Predicting Persistent Organ Failure and Pancreatic Necrosis in Acute Pancreatitis: A Post Hoc Analysis of Three Large Prospective Databases.

Predicting severe acute pancreatitis (AP) remains a challenge. The present study compares admission blood urea nitrogen (BUN), hematocrit, and creatinine, as well as changes in their levels over 24 h, aiming to determine the most accurate laboratory test for predicting persistent organ failure and pancreatic necrosis. Clinical data of 1,612 AP patients, enrolled prospectively in three independent cohorts (University of Pittsburgh, Brigham and Women's Hospital, Dutch Pancreatitis Study Group), were abstracted. The predictive accuracy of the studied laboratories was measured using area under the receiver-operating characteristic curve (AUC) analysis. A pooled analysis was conducted to determine their impact on the risk for persistent organ failure and pancreatic necrosis. Finally, a classification tree was developed on the basis of the most accurate laboratory parameters. Admission hematocrit ≥44% and rise in BUN at 24 h were the most accurate in predicting persistent organ failure (AUC: 0.67 and 0.71, respectively) and pancreatic necrosis (0.66 and 0.67, respectively), outperforming the other laboratory parameters and the acute physiology and chronic health evaluation-II score. In a pooled analysis, admission hematocrit ≥44% and rise in BUN at 24 h were associated with an odds ratio of 3.54 and 5.84 for persistent organ failure, and 3.11 and 4.07, respectively, for pancreatic necrosis. In addition, the classification tree illustrated that when both admission hematocrit was ≥44% and BUN levels increased at 24 h, the rates of persistent organ failure and pancreatic necrosis reached 53.6% and 60.3%, respectively. Admission hematocrit ≥44% and rise in BUN at 24 h may be the optimal predictive tools in clinical practice among existing laboratory parameters and scoring systems.

Transluminal endoscopic step-up approach versus minimally invasive surgical step-up approach in patients with infected necrotising pancreatitis (TENSION trial): design and rationale of a randomised controlled multicenter trial [ISRCTN09186711

BackgroundInfected necrotising pancreatitis is a potentially lethal disease that nearly always requires intervention. Traditionally, primary open necrosectomy has been the treatment of choice. In recent years, the surgical step-up approach, consisting of percutaneous catheter drainage followed, if necessary, by (minimally invasive) surgical necrosectomy has become the standard of care. A promising minimally invasive alternative is the endoscopic transluminal step-up approach. This approach consists of endoscopic transluminal drainage followed, if necessary, by endoscopic transluminal necrosectomy. We hypothesise that the less invasive endoscopic step-up approach is superior to the surgical step-up approach in terms of clinical and economic outcomes.Methods/DesignThe TENSION trial is a randomised controlled, parallel-group superiority multicenter trial. Patients with (suspected) infected necrotising pancreatitis with an indication for intervention and in whom both treatment modalities are deemed possible, will be randomised to either an endoscopic transluminal or a surgical step-up approach. During a 4 year study period, 98 patients will be enrolled from 24 hospitals of the Dutch Pancreatitis Study Group. The primary endpoint is a composite of death and major complications within 6 months following randomisation. Secondary endpoints include complications such as pancreaticocutaneous fistula, exocrine or endocrine pancreatic insufficiency, need for additional radiological, endoscopic or surgical intervention, the need for necrosectomy after drainage, the number of (re-)interventions, quality of life, and total direct and indirect costs.DiscussionThe TENSION trial will answer the question whether an endoscopic step-up approach reduces the combined primary endpoint of death and major complications, as well as hospital stay and related costs compared with a surgical step-up approach in patients with infected necrotising pancreatitis.

Pancreatitis of biliary origin, optimal timing of cholecystectomy (PONCHO trial): study protocol for a randomized controlled trial

BackgroundAfter an initial attack of biliary pancreatitis, cholecystectomy minimizes the risk of recurrent biliary pancreatitis and other gallstone-related complications. Guidelines advocate performing cholecystectomy within 2 to 4 weeks after discharge for mild biliary pancreatitis. During this waiting period, the patient is at risk of recurrent biliary events. In current clinical practice, surgeons usually postpone cholecystectomy for 6 weeks due to a perceived risk of a more difficult dissection in the early days following pancreatitis and for logistical reasons. We hypothesize that early laparoscopic cholecystectomy minimizes the risk of recurrent biliary pancreatitis or other complications of gallstone disease in patients with mild biliary pancreatitis without increasing the difficulty of dissection and the surgical complication rate compared with interval laparoscopic cholecystectomy.Methods/DesignPONCHO is a randomized controlled, parallel-group, assessor-blinded, superiority multicenter trial. Patients are randomly allocated to undergo early laparoscopic cholecystectomy, within 72 hours after randomization, or interval laparoscopic cholecystectomy, 25 to 30 days after randomization. During a 30-month period, 266 patients will be enrolled from 18 hospitals of the Dutch Pancreatitis Study Group. The primary endpoint is a composite endpoint of mortality and acute re-admissions for biliary events (that is, recurrent biliary pancreatitis, acute cholecystitis, symptomatic/obstructive choledocholithiasis requiring endoscopic retrograde cholangiopancreaticography including cholangitis (with/without endoscopic sphincterotomy), and uncomplicated biliary colics) occurring within 6 months following randomization. Secondary endpoints include the individual endpoints of the composite endpoint, surgical and other complications, technical difficulty of cholecystectomy and costs.DiscussionThe PONCHO trial is designed to show that early laparoscopic cholecystectomy (within 72 hours) reduces the combined endpoint of mortality and re-admissions for biliary events as compared with interval laparoscopic cholecystectomy (between 25 and 30 days) after recovery of a first episode of mild biliary pancreatitis.Trial registrationCurrent Controlled Trials: ISRCTN72764151

Endoscopic transluminal step-up approach versus surgical step-up approach in patients with infected necrotizing pancreatitis (TENSION): Design and rationale of a randomized controlled multicenter trial

s / Pancreatology 12 (2012) 502–597 575 showed that endoscopic necrosectomy significantly reduced the proinflammatory response as well as complications and death compared to surgical necrosectomy. These preliminary outcomes require confirmation in a larger trial. We describe the design and rationale of a nationwide study called TENSION: “Endoscopic transluminal step-up approach versus surgical step-up approach in patients with infected necrotizing pancreatitis” (Trial registration: ISRCTN09186711). Methods: The TENSION trial is a randomized controlled parallel-group, superiority multicenter trial. Patients with infected necrotizing pancreatitis will be randomized to an endoscopic or surgical step-up approach. The endoscopic step-up approach consists of endoscopic transluminal drainage followed, if necessary, by endoscopic transluminal necrosectomy. The surgical step-up approach consists of percutaneous catheter drainage, if necessary, followed by video-assisted retroperitoneal debridement (VARD). The primary endpoint is a composite of major complications (i.e., new onset organ failure, bleeding requiring intervention, perforation of a visceral organ requiring intervention, enterocutaneous fistula requiring intervention and incisional hernia) or death within 6 months following randomization. Secondary endpoints include other complications such as pancreatic fistula, pancreatic insufficiency, length of intensive careand hospital stay, quality of life, and costs. 98 patients will be enrolled in 25 hospitals of the Dutch Pancreatitis Study Group in a 3-year period. Conclusion: The TENSION trial is designed to evaluate if an endoscopic step-up approach is superior to a surgical step-up approach in terms of clinical outcomes and cost-effectiveness in patients with infected necrotizing pancreatitis.

Blood Urea Nitrogen in the Early Assessment of Acute Pancreatitis

Objective assessment of acute pancreatitis (AP) is critical to help guide resuscitation efforts. Herein we (1) validate serial blood urea nitrogen (BUN) measurement for early prediction of mortality and (2) develop an objective BUN-based approach to early assessment in AP. We performed a secondary analysis of 3 prospective AP cohort studies: Brigham and Women's Hospital (BWH), June 2005 through May 2009; the Dutch Pancreatitis Study Group (DPSG), March 2004 through March 2007; and the University of Pittsburgh Medical Center (UPMC), June 2003 through September 2007. Meta-analysis and stratified multivariate logistic regression adjusted for age, sex, and creatinine levels were calculated to determine risk of mortality associated with elevated BUN level at admission and rise in BUN level at 24 hours. The accuracy of the BUN measurements was determined by area under the receiver operating characteristic curve (AUC) analysis compared with serum creatinine measurement and APACHE II score. A BUN-based assessment algorithm was derived on BWH data and validated on the DPSG and UPMC cohorts. A total of 1043 AP cases were included in analysis. In pooled analysis, a BUN level of 20 mg/dL or higher was associated with an odds ratio (OR) of 4.6 (95% confidence interval [CI], 2.5-8.3) for mortality. Any rise in BUN level at 24 hours was associated with an OR of 4.3 (95% CI, 2.3-7.9) for death. Accuracy of serial BUN measurement (AUC, 0.82-0.91) was comparable to that of the APACHE II score (AUC, 0.72-0.92) in each of the cohorts. A BUN-based assessment algorithm identified patients at increased risk for mortality during the initial 24 hours of hospitalization. We have confirmed the accuracy of BUN measurement for early prediction of mortality in AP and developed an algorithm that may assist physicians in their early resuscitation efforts.

474 Simultaneous Nasogastric Decompression with Mid-Jejunal Feeding Avoids Total Parenteral Nutrition (TPN) and Early Surgery in the Management of Complicated Acute Pancreatitis and Gastric Outlet Obstruction

G A A b st ra ct s Methods: During 2003-2007, all patients with predicted severe acute pancreatitis (Acute Physiology and Chronic Health Evaluation [APACHE-II] score ≥8, or Imrie/modified Glasgow score ≥3, or C-reactive protein [CRP] >150 mg/L) were prospectively included in 15 hospitals in the Dutch ‘probiotics in acute pancreatitis trial' (PROPATRIA). All patients received EN via a nasojejunal feeding tube. The time between admission and start of EN, however, varied between patients (at the discretion of the treating physician).Two groups were retrospectively defined: 1) the ‘early EN group' (start of EN within 48 hours after admission) and 2) the ‘standard EN group' (start after 48 hours after admission). Groups were compared for the total number of infectious complications: pneumonia, bacteremia and infected necrosis. Multivariate logistic regression was used to adjust for differences at baseline (p<0.2) and predicted disease severity (APACHE-II score). Results: The early (n= 184) and standard (n=112) EN groups were highly comparable at baseline for APACHE-II score, C-reactive protein, Imrie-score, computed tomography severity index and the presence of (multi)organ failure. Infectious complications occurred in 49 patients (27%) in the early EN group versus in 38 patients (34%) in the standard EN group (adjusted odds ratio [OR] 0.659, 95%-confidence interval [CI] 0.33-1.33, p=.244). Early EN was associated with a reduction of bacteremia (14% versus 27%; adjusted OR 0.389, 95%-CI 0.17-0.88, p=.024). No reduction of infected necrosis (11% versus 13%, p=.853) or pneumonia (16% versus 14%, p=.861) was observed. Conclusion: An early start of enteral nutrition may prevent bacteremia and hence improve outcome in patients with predicted severe acute pancreatitis. To this end, the Dutch Pancreatitis Study Group has recently started a nationwide randomized controlled trial comparing an early start of EN with standard therapy in predicted severe acute pancreatitis.