Objective: To compare the long-term outcomes of immediate drainage versus the postponed-drainage approach in patients with infected necrotizing pancreatitis.Background: In the randomized POINTER... Show moreObjective: To compare the long-term outcomes of immediate drainage versus the postponed-drainage approach in patients with infected necrotizing pancreatitis.Background: In the randomized POINTER trial, patients assigned to the postponed-drainage approach using antibiotic treatment required fewer interventions, as compared with immediate drainage, and over a third were treated without any intervention.Methods: Clinical data of those patients alive after the initial 6-month follow-up were re-evaluated. The primary outcome was a composite of death and major complications.Results: Out of 104 patients, 88 were re-evaluated with a median follow-up of 51 months. After the initial 6-month follow-up, the primary outcome occurred in 7 of 47 patients (15%) in the immediate-drainage group and 7 of 41 patients (17%) in the postponed-drainage group (RR 0.87, 95% CI 0.33–2.28; P=0.78). Additional drainage procedures were performed in 7 patients (15%) versus 3 patients (7%) (RR 2.03; 95% CI 0.56–7.37; P=0.34). The median number of additional interventions was 0 (IQR 0–0) in both groups (P=0.028). In the total follow-up, the median number of interventions was higher in the immediate-drainage group than in the postponed-drainage group (4 vs. 1, P=0.001). Eventually, 14 of 15 patients (93%) in the postponed-drainage group who were successfully treated in the initial 6-month follow-up with antibiotics and without any intervention remained without intervention. At the end of follow-up, pancreatic function and quality of life were similar.Conclusions: Also, during long-term follow-up, a postponed-drainage approach using antibiotics in patients with infected necrotizing pancreatitis results in fewer interventions as compared with immediate drainage and should therefore be the preferred approach. Show less
Background and AimMore insight into the incidence of and factors associated with progression following a first episode of acute pancreatitis (AP) would offer opportunities for improvements in... Show moreBackground and AimMore insight into the incidence of and factors associated with progression following a first episode of acute pancreatitis (AP) would offer opportunities for improvements in disease management and patient counseling.MethodsA long-term post hoc analysis of a prospective cohort of patients with AP (2008-2015) was performed. Primary endpoints were recurrent acute pancreatitis (RAP), chronic pancreatitis (CP), and pancreatic cancer. Cumulative incidence calculations and risk analyses were performed.ResultsOverall, 1184 patients with a median follow-up of 9 years (IQR: 7-11) were included. RAP and CP occurred in 301 patients (25%) and 72 patients (6%), with the highest incidences observed for alcoholic pancreatitis (40% and 22%). Pancreatic cancer was diagnosed in 14 patients (1%). Predictive factors for RAP were alcoholic and idiopathic pancreatitis (OR 2.70, 95% CI 1.51-4.82 and OR 2.06, 95% CI 1.40-3.02), and no pancreatic interventions (OR 1.82, 95% CI 1.10-3.01). Non-biliary etiology (alcohol: OR 5.24, 95% CI 1.94-14.16, idiopathic: OR 4.57, 95% CI 2.05-10.16, and other: OR 2.97, 95% CI 1.11-7.94), RAP (OR 4.93, 95% CI 2.84-8.58), prior pancreatic interventions (OR 3.10, 95% CI 1.20-8.02), smoking (OR 2.33, 95% CI 1.14-4.78), and male sex (OR 2.06, 95% CI 1.05-4.05) were independently associated with CP.ConclusionDisease progression was observed in a quarter of pancreatitis patients. We identified several risk factors that may be helpful to devise personalized strategies with the intention to reduce the impact of disease progression in patients with AP. Show less
Background/objectives: The most important risk factor for recurrent pancreatitis after an episode of acute alcoholic pancreatitis is continuation of alcohol use. Current guidelines do not recommend... Show moreBackground/objectives: The most important risk factor for recurrent pancreatitis after an episode of acute alcoholic pancreatitis is continuation of alcohol use. Current guidelines do not recommend any specific treatment strategy regarding alcohol cessation. The PANDA trial investigates whether implementation of a structured alcohol cessation support program prevents pancreatitis recurrence after a first episode of acute alcoholic pancreatitis.Methods: PANDA is a nationwide cluster randomised superiority trial. Participating hospitals are randomised for the investigational management, consisting of a structured alcohol cessation support program, or current practice. Patients with a first episode of acute pancreatitis caused by harmful drinking (AUDIT score >7 and < 16 for men and >6 and < 14 for women) will be included. The primary endpoint is recurrence of acute pancreatitis. Secondary endpoints include cessation or reduction of alcohol use, other alcohol-related diseases, mortality, quality of life, quality-adjusted life years (QALYs) and costs. The follow-up period comprises one year after inclusion.Discussion: This is the first multicentre trial with a cluster randomised trial design to investigate whether a structured alcohol cessation support program reduces recurrent acute pancreatitis in patients after a first episode of acute alcoholic pancreatitis, as compared with current practice. (c) 2023 The Author(s). Published by Elsevier B.V. on behalf of IAP and EPC. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Groenen, H.; Jalalzadeh, H.; Buis, D.R.; Dreissen, Y.E.M.; Goosen, J.H.M.; Griekspoor, M.; ... ; Boermeester, M.A. 2023
BackgroundThe evidence on prophylactic use of negative pressure wound therapy on primary closed incisional wounds (iNPWT) for the prevention of surgical site infections (SSI) is confusing and... Show moreBackgroundThe evidence on prophylactic use of negative pressure wound therapy on primary closed incisional wounds (iNPWT) for the prevention of surgical site infections (SSI) is confusing and ambiguous. Implementation in daily practice is impaired by inconsistent recommendations in current international guidelines and published meta-analyses. More recently, multiple new randomised controlled trials (RCTs) have been published. We aimed to provide an overview of all meta-analyses and their characteristics; to conduct a new and up-to-date systematic review and meta-analysis and Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment; and to explore the additive value of new RCTs with a trial sequential analysis (TSA).MethodsPubMed, Embase and Cochrane CENTRAL databases were searched from database inception to October 24, 2022. We identified existing meta-analyses covering all surgical specialties and RCTs studying the effect of iNPWT compared with standard dressings in all types of surgery on the incidence of SSI, wound dehiscence, reoperation, seroma, hematoma, mortality, readmission rate, skin blistering, skin necrosis, pain, and adverse effects of the intervention. We calculated relative risks (RR) with corresponding 95% confidence intervals (CI) using a Mantel-Haenszel random-effects model. We assessed publication bias with a comparison-adjusted funnel plot. TSA was used to assess the risk of random error. The certainty of evidence was evaluated using the Cochrane Risk of Bias-2 (RoB2) tool and GRADE approach. This study is registered with PROSPERO, CRD42022312995.FindingsWe identified eight previously published general meta-analyses investigating iNPWT and compared their results to present meta-analysis. For the updated systematic review, 57 RCTs with 13,744 patients were included in the quantitative analysis for SSI, yielding a RR of 0.67 (95% CI: 0.59–0.76, I2 = 21%) for iNPWT compared with standard dressing. Certainty of evidence was high. Compared with previous meta-analyses, the RR stabilised, and the confidence interval narrowed. In the TSA, the cumulative Z-curve crossed the trial sequential monitoring boundary for benefit, confirming the robustness of the summary effect estimate from the meta-analysis.InterpretationIn this up-to-date meta-analysis, GRADE assessment shows high-certainty evidence that iNPWT is effective in reducing SSI, and uncertainty is less than in previous meta-analyses. TSA indicated that further trials are unlikely to change the effect estimate for the outcome SSI; therefore, if future research is to be conducted on iNPWT, it is crucial to consider what the findings will contribute to the existing robust evidence. Show less
BACKGROUND & AIMS: Previous randomized trials, including the Transluminal Endoscopic Step-Up Approach Versus Minimally Invasive Surgical Step-Up Approach in Patients With Infected Pancreatic... Show moreBACKGROUND & AIMS: Previous randomized trials, including the Transluminal Endoscopic Step-Up Approach Versus Minimally Invasive Surgical Step-Up Approach in Patients With Infected Pancreatic Necrosis (TENSION) trial, demonstrated that the endoscopic step-up approach might be preferred over the surgical step-up approach in patients with infected necrotizing pancreatitis based on favorable short-term outcomes. We compared long-term clinical outcomes of both step-up approaches after a period of at least 5 years. METHODS: In this long-term follow-up study, we reevaluated all clinical data on 83 patients (of the originally 98 included patients) from the TENSION trial who were still alive after the initial 6-month follow-up. The primary end point, similar to the TENSION trial, was a composite of death and major complications. Secondary end points included individual major complications, pancreaticocutaneous fistula, reinterventions, pancreatic insufficiency, and quality of life. RESULTS: After a mean followup period of 7 years, the primary end point occurred in 27 patients (53%) in the endoscopy group and in 27 patients (57%) in the surgery group (risk ratio [RR], 0.93; 95% confidence interval [CI], 0.65-1.32; P = .688). Fewer pancreaticocutaneous fistulas were identified in the endoscopy group (8% vs 34%; RR, 0.23; 95% CI, 0.08-0.83). After the initial 6-month follow-up, the endoscopy group needed fewer reinterventions than the surgery group (7% vs 24%; RR, 0.29; 95% CI, 0.09-0.99). Pancreatic insufficiency and quality of life did not differ between groups. CONCLUSIONS: At long-term follow-up, the endoscopic step-up approach was not superior to the surgical step-up approach in reducing death or major complications in patients with infected necrotizing pancreatitis. However, patients assigned to the endoscopic approach developed overall fewer pancreaticocutaneous fistulas and needed fewer reinterventions after the initial 6-month follow-up. Show less
Background & AimsPrevious randomized trials, including the Transluminal Endoscopic Step-Up Approach Versus Minimally Invasive Surgical Step-Up Approach in Patients With Infected Pancreatic Necrosis... Show moreBackground & AimsPrevious randomized trials, including the Transluminal Endoscopic Step-Up Approach Versus Minimally Invasive Surgical Step-Up Approach in Patients With Infected Pancreatic Necrosis (TENSION) trial, demonstrated that the endoscopic step-up approach might be preferred over the surgical step-up approach in patients with infected necrotizing pancreatitis based on favorable short-term outcomes. We compared long-term clinical outcomes of both step-up approaches after a period of at least 5 years.MethodsIn this long-term follow-up study, we reevaluated all clinical data on 83 patients (of the originally 98 included patients) from the TENSION trial who were still alive after the initial 6-month follow-up. The primary end point, similar to the TENSION trial, was a composite of death and major complications. Secondary end points included individual major complications, pancreaticocutaneous fistula, reinterventions, pancreatic insufficiency, and quality of life.ResultsAfter a mean follow-up period of 7 years, the primary end point occurred in 27 patients (53%) in the endoscopy group and in 27 patients (57%) in the surgery group (risk ratio [RR], 0.93; 95% confidence interval [CI], 0.65–1.32; P = .688). Fewer pancreaticocutaneous fistulas were identified in the endoscopy group (8% vs 34%; RR, 0.23; 95% CI, 0.08–0.83). After the initial 6-month follow-up, the endoscopy group needed fewer reinterventions than the surgery group (7% vs 24%; RR, 0.29; 95% CI, 0.09–0.99). Pancreatic insufficiency and quality of life did not differ between groups.ConclusionsAt long-term follow-up, the endoscopic step-up approach was not superior to the surgical step-up approach in reducing death or major complications in patients with infected necrotizing pancreatitis. However, patients assigned to the endoscopic approach developed overall fewer pancreaticocutaneous fistulas and needed fewer reinterventions after the initial 6-month follow-up. Netherlands Trial Register no: NL8571. Show less
Kempeneers, M.A.; Hemert, A.K.E. van; Hoek, M. van der; Issa, Y.; Hooft, J.E. van; Nio, C.Y.; ... ; Boermeester, M.A. 2022
Background Surgery is the most effective treatment in patients with painful chronic pancreatitis and a dilated pancreatic duct. Studies reporting the outcomes of selected surgical approach... Show moreBackground Surgery is the most effective treatment in patients with painful chronic pancreatitis and a dilated pancreatic duct. Studies reporting the outcomes of selected surgical approach according to the pancreatic head size in these patients are lacking. Method This was a retrospective, observational single-centre study of consecutive patients who underwent either a Frey procedure or extended lateral pancreaticojejunostomy (eLPJ) for pain due to chronic pancreatitis with a dilated main pancreatic duct (5 mm or more) between 2006 and 2017. A Frey procedure was used in patients with pancreatic head enlargement (40 mm or more) and eLPJ (full-length pancreaticojejunostomy, including transection of the gastroduodenal artery) in others. A biliodigestive bypass was added in the case of biliary obstruction. Results Overall, 140 of 220 patients met the eligibility criteria: 70 underwent a Frey procedure and 70 an eLPJ. Hepaticojejunostomy was added in 17.1 per cent of patients (Frey: 24.3 per cent; eLPJ: 10.0 per cent (P = 0.025)). Major morbidity occurred in 15.0 per cent of patients (Frey: 21.4 per cent; eLPJ: 8.6 per cent (P = 0.033)). After a median 7.8 years of follow-up, the mean (s.d.) decrease in Izbicki pain score was 33 (27) points (34 (28) points after a Frey procedure; 32 (26) points after an eLPJ). Pain relief was reported as 'very much' by 87.5 per cent of patients (Frey: 86.1 per cent; eLPJ: 88.9 per cent) and as 'partial' by 11.1 per cent (Frey: 13.8 per cent; eLPJ: 8.3 per cent). Conclusion Selective-use of either a Frey procedure or eLPJ in patients with symptomatic chronic pancreatitis was-associated with low morbidity and long-term pain relief. Adding a-biliodigestive bypass did not increase morbidity.Studies reporting on short- and long-term outcomes of Frey and extended lateral pancreaticojejunostomy (eLPJ) in chronic pancreatitis are lacking. In 140 consecutive patients the rate of major morbidity was 15 per cent (Frey: 21 per cent; eLPJ: 9 per cent). After median follow-up of 7.8 years in 75 patients, mean (s.d.) decrease in Izbicki pain score was 33 (27) points (Frey: 34 (28); eLPJ: 32 (26)) and pain relief was reported as 'very much' by 88 per cent of patients (Frey: 86 per cent; eLPJ: 89 per cent). Show less
Strijker, M.; Sijde, F. van der; Suker, M.; Boermeester, M.A.; Bonsing, B.A.; Bruno, M.J.; ... ; Bijlsma, M.F. 2021
Background: We evaluated the stroma marker A Disintegrin And Metalloprotease 12 (ADAM12) as a preoperative prognostic and treatment-predictive marker for overall survival (OS) in pancreatic ductal... Show moreBackground: We evaluated the stroma marker A Disintegrin And Metalloprotease 12 (ADAM12) as a preoperative prognostic and treatment-predictive marker for overall survival (OS) in pancreatic ductal adenocarcinoma (PDAC) and periampullary cancers.Methods: Materials were derived from the prospective nationwide Dutch Pancreas Biobank (2015-2017). We included patients who underwent resection because of PDAC/periampullary cancer or non-invasive IPMN (control group) and had a preoperative serum sample available. ADAM12 levels were dichotomized using a pre-defined cut-off (316 pg/mL). Univariable and multivariable Cox regression analyses (backward selection) were performed.Results: Median ADAM12 levels were 161 (IQR 79-352) pg/mL in 215 PDAC and periampullary adenocarcinomas. High ADAM12 levels (>316 pg/mL) predicted poor OS in the total group of pancreatic and periampullary adenocarcinomas (P = 0.04), but not after adjustment. In distal cholangiocarcinoma (n = 33), high ADAM12 levels predicted poor OS in univariable analysis (P = 0.02), but not in PDAC (P = 0.63). PDAC patients (n = 135) with high ADAM12 levels benefited from adjuvant treatment (median OS 27 vs 14 months, P = 0.02), whereas those with low levels did not (21 vs 21 months, P = 0.87).Conclusion: High circulating ADAM12 levels, as a proxy for activated stroma, predict survival benefit from adjuvant chemotherapy in PDAC, requiring validation in future studies. Show less
BACKGROUNDInfected 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... Show moreBACKGROUNDInfected 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.METHODSWe 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.RESULTSA 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.CONCLUSIONSThis 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. Show less
Meer, J.H.M. van der; Boer, R.J. de; Meijer, B.J.; Smit, W.L.; Vermeulen, J.L.M.; Meisner, S.; ... ; Muncan, V. 2021
The epithelial signaling pathways involved in damage and regeneration, and neoplastic transformation are known to be similar. We noted upregulation of argininosuccinate synthetase (ASS1) in... Show moreThe epithelial signaling pathways involved in damage and regeneration, and neoplastic transformation are known to be similar. We noted upregulation of argininosuccinate synthetase (ASS1) in hyperproliferative intestinal epithelium. Since ASS1 leads to de novo synthesis of arginine, an important amino acid for the growth of intestinal epithelial cells, its upregulation can contribute to epithelial proliferation necessary to be sustained during oncogenic transformation and regeneration. Here we investigated the function of ASS1 in the gut epithelium during tissue regeneration and tumorigenesis, using intestinal epithelial conditional Ass1 knockout mice and organoids, and tissue specimens from colorectal cancer patients. We demonstrate that ASS1 is strongly expressed in the regenerating and Apc-mutated intestinal epithelium. Furthermore, we observe an arrest in amino acid flux of the urea cycle, which leads to an accumulation of intracellular arginine. However, loss of epithelial Ass1 does not lead to a reduction in proliferation or increase in apoptosis in vivo, also in mice fed an arginine-free diet. Epithelial loss of Ass1 seems to be compensated by altered arginine metabolism in other cell types and the liver. Show less
Kempeneers, M.A.; Issa, Y.; Verdonk, R.C.; Bruno, M.; Fockens, P.; Goor, H. van; ... ; Dutch Pancreatitis Study Grp 2021
Objective Pain in chronic pancreatitis is subdivided in a continuous or intermittent pattern, each thought to represent a different entity, requiring specific treatment. Because evidence is missing... Show moreObjective Pain in chronic pancreatitis is subdivided in a continuous or intermittent pattern, each thought to represent a different entity, requiring specific treatment. Because evidence is missing, we studied pain patterns in a prospective longitudinal nationwide study.Design 1131 patients with chronic pancreatitis (fulfilling M-ANNHEIM criteria) were included between 2011 and 2018 in 30 Dutch hospitals. Patients with continuous or intermittent pain were compared for demographics, pain characteristics, quality of life (Short-Form 36), imaging findings, disease duration and treatment. Alternation of pain pattern and associated variables were longitudinally assessed using a multivariable multinomial logistic regression model.Results At inclusion, 589 patients (52%) had continuous pain, 231 patients (20%) had intermittent pain and 311 patients (28%) had no pain. Patients with continuous pain had more severe pain, used more opioids and neuropathic pain medication, and had a lower quality of life. There were no differences between pain patterns for morphological findings on imaging, disease duration and treatment. During a median follow-up of 47 months, 552 of 905 patients (61%) alternated at least once between pain patterns. All alternations were associated with the Visual Analogue Scale pain intensity score and surgery was only associated with the change from pain to no pain.Conclusion Continuous and intermittent pain patterns in chronic pancreatitis do not seem to be the result of distinctly different pathophysiological entities. The subjectively reported character of pain is not related to imaging findings or disease duration. Pain patterns often change over time and are merely a feature of how severity of pain is experienced. Show less
Berg, F.F. van den; Issa, Y.; Vreijling, J.P.; Lerch, M.M.; Weiss, F.U.; Besselink, M.G.; ... ; Santvoort, H.C. van 2021
Young patients are thought to have a more severe disease course and a higher rate of recurrent diverticulitis. However, these understandings are mainly based on studies with important limitations.... Show moreYoung patients are thought to have a more severe disease course and a higher rate of recurrent diverticulitis. However, these understandings are mainly based on studies with important limitations. This review aimed to clarify the true natural history of acute diverticulitis in young patients compared to elderly patients. PubMed and MEDLINE were searched for studies reporting outcomes on disease severity or recurrences in young and elderly patients with a computed tomography-proven diagnosis of acute diverticulitis. Twenty-seven studies were included. The proportion of complicated diverticulitis at presentation (21 studies) was not different for young patients (age cut-off 40-50 years) compared to elderly patients [risk ratio (RR) 1.19; 95% confidence interval 0.94-1.50]. The need for emergency surgery (11 studies) or percutaneous abscess drainage (two studies) yielded comparable results for both groups with a RR of 0.93 (95% confidence interval 0.70-1.24) and 1.65 (95% confidence interval 0.60-4.57), respectively. Crude data on recurrent diverticulitis rates (12 studies) demonstrated a significantly higher RR of 1.47 (95% confidence interval 1.20-1.80) for young patients. Notably, no association between age and recurrent diverticulitis was found in the studies that used survival analyses, taking length of follow-up per age group into account. In conclusion, young patients do not have a more severe course of acute diverticulitis. Published data on the risk of recurrent diverticulitis in young patients are conflicting, but those with the most robust design do not demonstrate an increased risk. Therefore, young patients should not be treated more aggressively nor have a lower threshold for elective surgery just because of their age. Show less
IMPORTANCE For patients with painful chronic pancreatitis, surgical treatment is postponed until medical and endoscopic treatment have failed. Observational studies have suggested that earlier... Show moreIMPORTANCE 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.OBJECTIVE To determine whether early surgery is more effective than the endoscopy-first approach in terms of clinical outcomes.DESIGN, SETTING, AND PARTICIPANTS 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.INTERVENTIONS 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.MAIN OUTCOMES AND MEASURES 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.RESULTS 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.CONCLUSIONS AND RELEVANCE 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. Show less
Introduction 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... Show moreIntroduction 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. Methods and analysis 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. Ethics and dissemination 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. Show less
