Long-Term Outcome of Immediate Versus Postponed Intervention in Patients With Infected Necrotizing Pancreatitis (POINTER): Multicenter Randomized Trial.

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 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. TRIAL REGISTRATION: ISRCTN33682933.

Detecting Colorectal Adenomas and Cancer Using Volatile Organic Compounds in Exhaled Breath: A Proof-of-Principle Study to Improve Screening.

INTRODUCTION: Early detection of colorectal cancer (CRC) by screening programs is crucial because survival rates worsen at advanced stages. However, the currently used screening method, the fecal immunochemical test (FIT), suffers from a high number of false-positives and is insensitive for detecting advanced adenomas (AAs), resulting in false-negatives for these premalignant lesions. Therefore, more accurate, noninvasive screening tools are needed. In this study, the utility of analyzing volatile organic compounds (VOCs) in exhaled breath in a FIT-positive population to detect the presence of colorectal neoplasia was studied. METHODS: In this multicenter prospective study, breath samples were collected from 382 FIT-positive patients with subsequent colonoscopy participating in the national Dutch bowel screening program (n = 84 negative controls, n = 130 non-AAs, n = 138 AAs, and n = 30 CRCs). Precolonoscopy exhaled VOCs were analyzed using thermal desorption-gas chromatography-mass spectrometry, and the data were preprocessed and analyzed using machine learning techniques. RESULTS: Using 10 discriminatory VOCs, AAs could be distinguished from negative controls with a sensitivity and specificity of 79% and 70%, respectively. Based on this biomarker profile, CRC and AA combined could be discriminated from controls with a sensitivity and specificity of 77% and 70%, respectively, and CRC alone could be discriminated from controls with a sensitivity and specificity of 80% and 70%, respectively. Moreover, the feasibility to discriminate non-AAs from controls and AAs was shown. DISCUSSION: VOCs in exhaled breath can detect the presence of AAs and CRC in a CRC screening population and may improve CRC screening in the future.

Endoscopic Versus Surgical Step-Up Approach for Infected Necrotizing Pancreatitis (ExTENSION): Long-term Follow-up of a Randomized Trial.

BACKGROUND & 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 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. 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. Netherlands Trial Register no: NL8571.

Endoscopic full-thickness resection of T1 colorectal cancers: a retrospective analysis from a multicenter Dutch eFTR registry.

BACKGROUND: Complete endoscopic resection and accurate histological evaluation for T1 colorectal cancer (CRC) are critical in determining subsequent treatment. Endoscopic full-thickness resection (eFTR) is a new treatment option for T1 CRC < 2 cm. We aimed to report clinical outcomes and short-term results. METHODS: Consecutive eFTR procedures for T1 CRC, prospectively recorded in our national registry between November 2015 and April 2020, were retrospectively analyzed. Primary outcomes were technical success and R0 resection. Secondary outcomes were histological risk assessment, curative resection, adverse events, and short-term outcomes. RESULTS: We included 330 procedures: 132 primary resections and 198 secondary scar resections after incomplete T1 CRC resection. Overall technical success, R0 resection, and curative resection rates were 87.0 % (95 % confidence interval [CI] 82.7 %-90.3 %), 85.6 % (95 %CI 81.2 %-89.2 %), and 60.3 % (95 %CI 54.7 %-65.7 %). Curative resection rate was 23.7 % (95 %CI 15.9 %-33.6 %) for primary resection of T1 CRC and 60.8 % (95 %CI 50.4 %-70.4 %) after excluding deep submucosal invasion as a risk factor. Risk stratification was possible in 99.3 %. The severe adverse event rate was 2.2 %. Additional oncological surgery was performed in 49/320 (15.3 %), with residual cancer in 11/49 (22.4 %). Endoscopic follow-up was available in 200/242 (82.6 %), with a median of 4 months and residual cancer in 1 (0.5 %) following an incomplete resection. CONCLUSIONS: eFTR is relatively safe and effective for resection of small T1 CRC, both as primary and secondary treatment. eFTR can expand endoscopic treatment options for T1 CRC and could help to reduce surgical overtreatment. Future studies should focus on long-term outcomes.

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: 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. 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 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. 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. (Funded by Fonds NutsOhra and Amsterdam UMC; POINTER ISRCTN Registry number, ISRCTN33682933.).

Evaluation of polypectomy quality indicators of large nonpedunculated colorectal polyps in a nonexpert, bowel cancer screening cohort.

BACKGROUND AND AIMS: With the introduction of the national bowel cancer screening program, the detection of sessile and flat colonic lesions ≥20 mm in size, defined as large nonpedunculated colorectal polyps (LNPCPs), has increased. The aim of this study was to examine the quality of endoscopic treatment of LNPCPs in the Dutch screening program. METHODS: This investigation comprised 2 related, but separate, substudies (1 with a cross-sectional design and 1 with a longitudinal design). The first examined prevalence and characteristics of LNPCPs in data from the national Dutch screening cohort from February 2014 until January 2017. The second, with screening data from 5 endoscopy units in the Southern part of the Netherlands from February 2014 until August 2015, examined performance on important quality indicators (technical and clinical successes, recurrence rate, adverse event rate, and surgery referral rate). All patients were part of the national Dutch screening cohort. RESULTS: In the national cohort, an LNPCP was detected in 8% of participants. Technical and clinical success decreased with increasing LNPCP size, from 93% and 96% in 20- to 29-mm lesions to 85% and 86% in 30- to 39-mm lesions and to 74% and 81% in ≥40-mm lesions (P < .001; P = .034). The cumulative recurrence rate at 12 months increased with LNPCP size, from 9% to 22% and 26% in the respective size groups (P = .095). The adverse event rate was 5%. The overall surgical referral rate for noninvasive LNPCPs was 7%. CONCLUSIONS: In this performance of 2 substudies, it was shown that quality parameters for endoscopic resection of large polyps in the Dutch screening cohort are not reached, especially in ≥30-mm polyps. Endoscopic resection of large polyps could benefit from additional training, quality monitoring, and centralization either within or between centers.

Gastric peroral endoscopic pyloromyotomy for decompensated gastroparesis: comprehensive motility analysis in relation to treatment outcomes.

Background and study aims There are no reliable data to predict which patients with gastroparesis (GP) would benefit the most from gastric peroral endoscopic pyloromyotomy (G-POEM). The aim of the present study was to assess whether antro-duodenal motility patterns and pyloric distensibility can predict the outcome of G-POEM in patients with decompensated GP. Patients and methods In an open-label study, patients with GP and refractory symptoms were eligible for treatment with G-POEM if treatment attempts according to a standardized stepwise protocol had failed. Baseline assessment included Gastroparesis Cardinal Symptom Index (GCSI), C13-octanoic gastric emptying breath test and high-resolution antro-duodenal manometry. Pyloric distensibility using EndoFlip measurements was assessed at baseline and 3 months after the procedure. Explorative analyses were performed on potential predictors of response using logistic regression analyses. Results Twenty-four patients with decompensated GP underwent G-POEM. At baseline, 78.3 % and 61.9 % of patients showed antral hypomotility and neuropathic motor patterns, respectively. The technical success rate was 100 % (24/24). Mean GCSI improved significantly at 3, 6, and 12 months after G-POEM ( P  = 0.01). Median distensibility index (DI) improved significantly as compared with baseline (7.5 [6.9;11.7] vs. 5.3[3.1;8.1], P  = 0.004). A significant correlation was found between clinical response at 6 months and pyloric DI improvement ( P  = 0.003). No potential predictors of clinical response after G-POEM could be identified in an explorative analysis. Conclusions G-POEM improved pyloric distensibility patterns in patients with decompensated GP. Clinical response at 6 months after G-POEM was associated with pyloric distensibility improvement. However, no potential predictors of response could be identified from either antro-duodenal motility patterns or pyloric distensibility.

Clip placement to prevent delayed bleeding after colonic endoscopic mucosal resection (CLIPPER): study protocol for a randomized controlled trial.

BACKGROUND: Endoscopic mucosal resection (EMR) for large colorectal polyps is in most cases the preferred treatment to prevent progression to colorectal carcinoma. The most common complication after EMR is delayed bleeding, occurring in 7% overall and in approximately 10% of polyps ≥ 2 cm in the proximal colon. Previous research has suggested that prophylactic clipping of the mucosal defect after EMR may reduce the incidence of delayed bleeding in polyps with a high bleeding risk. METHODS: The CLIPPER trial is a multicenter, parallel-group, single blinded, randomized controlled superiority study. A total of 356 patients undergoing EMR for large (≥ 2 cm) non-pedunculated polyps in the proximal colon will be included and randomized to the clip group or the control group. Prophylactic clipping will be performed in the intervention group to close the resection defect after the EMR with a distance of < 1 cm between the clips. Primary outcome is delayed bleeding within 30 days after EMR. Secondary outcomes are recurrent or residual polyps and clip artifacts during surveillance colonoscopy after 6 months, as well as cost-effectiveness of prophylactic clipping and severity of delayed bleeding. DISCUSSION: The CLIPPER trial is a pragmatic study performed in the Netherlands and is powered to determine the real-time efficacy and cost-effectiveness of prophylactic clipping after EMR of proximal colon polyps ≥ 2 cm in the Netherlands. This study will also generate new data on the achievability of complete closure and the effects of clip placement on scar surveillance after EMR, in order to further promote the debate on the role of prophylactic clipping in everyday clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT03309683 . Registered on 13 October 2017. Start recruitment: 05 March 2018. Planned completion of recruitment: 31 August 2021.

Metachronous neoplasms in patients with laterally spreading tumours during surveillance.

BACKGROUND: Laterally spreading tumours represent a major challenge for endoscopic detection and resection. OBJECTIVE: To examine synchronous and metachronous neoplasms in patients with laterally spreading tumours. METHODS: We prospectively collected colonoscopy and histopathology data from patients who underwent colonoscopy in our centre at up to 6 years' follow-up. Post-resection surveillance outcomes between laterally spreading tumours, flat colorectal neoplasms 10 mm or greater, and large polypoid colorectal neoplasms, polypoid colorectal neoplasms 10 mm or greater, were compared. RESULTS: Between 2008 and 2012, 8120 patients underwent colonoscopy for symptoms (84.6%), screening (6.7%) or surveillance (8.7%). At baseline, 151 patients had adenomatous laterally spreading tumours and 566 patients had adenomatous large polypoid colorectal neoplasms. Laterally spreading tumour patients had more synchronous colorectal neoplasms than large polypoid colorectal neoplasm patients (mean 3.34 vs. 2.34, p < 0.001). Laterally spreading tumour patients significantly more often developed metachronous colorectal neoplasms (71.6% vs. 54.2%, p = 0.0498) and colorectal neoplasms with high grade dysplasia/submucosal invasion than large polypoid colorectal neoplasm patients (36.4% vs. 15.8%, p < 0.001). After correction for age and gender, laterally spreading tumour patients were more likely than large polypoid colorectal neoplasm patients to develop a colorectal neoplasm with high grade dysplasia or submucosal invasion (hazard ratio 2.9, 95% confidence interval 1.8-4.6). The risk of metachronous colorectal cancer was not significantly different in laterally spreading tumours compared to large polypoid colorectal neoplasm patients. CONCLUSION: Patients with laterally spreading tumours developed more metachronous colorectal neoplasms with high grade dysplasia/submucosal invasion than large polypoid colorectal neoplasm patients. Based on these findings endoscopic treatment and surveillance recommendations for patients with laterally spreading tumours should be optimised.

Transanal minimally invasive surgery (TAMIS) versus endoscopic submucosal dissection (ESD) for resection of non-pedunculated rectal lesions (TRIASSIC study): study protocol of a European multicenter randomised controlled trial.

BACKGROUND: In the recent years two innovative approaches have become available for minimally invasive en bloc resections of large non-pedunculated rectal lesions (polyps and early cancers). One is Transanal Minimally Invasive Surgery (TAMIS), the other is Endoscopic Submucosal Dissection (ESD). Both techniques are standard of care, but a direct randomised comparison is lacking. The choice between either of these procedures is dependent on local expertise or availability rather than evidence-based. The European Society for Endoscopy has recommended that a comparison between ESD and local surgical resection is needed to guide decision making for the optimal approach for the removal of large rectal lesions in Western countries. The aim of this study is to directly compare both procedures in a randomised setting with regard to effectiveness, safety and perceived patient burden. METHODS: Multicenter randomised trial in 15 hospitals in the Netherlands. Patients with non-pedunculated lesions > 2 cm, where the bulk of the lesion is below 15 cm from the anal verge, will be randomised between either a TAMIS or an ESD procedure. Lesions judged to be deeply invasive by an expert panel will be excluded. The primary endpoint is the cumulative local recurrence rate at follow-up rectoscopy at 12 months. Secondary endpoints are: 1) Radical (R0-) resection rate; 2) Perceived burden and quality of life; 3) Cost effectiveness at 12 months; 4) Surgical referral rate at 12 months; 5) Complication rate; 6) Local recurrence rate at 6 months. For this non-inferiority trial, the total sample size of 198 is based on an expected local recurrence rate of 3% in the ESD group, 6% in the TAMIS group and considering a difference of less than 6% to be non-inferior. DISCUSSION: This is the first European randomised controlled trial comparing the effectiveness and safety of TAMIS and ESD for the en bloc resection of large non-pedunculated rectal lesions. This is important as the detection rate of these adenomas is expected to further increase with the introduction of colorectal screening programs throughout Europe. This study will therefore support an optimal use of healthcare resources in the future. TRIAL REGISTRATION: Netherlands Trial Register, NL7083 , 06 July 2018.

Optical diagnosis of diminutive polyps in the Dutch Bowel Cancer Screening Program: Are we ready to start?

Background and study aims Implementation of optical diagnosis of diminutive polyps may potentially increase the efficacy and cost-effectiveness of colonoscopies. To adopt such strategy in clinical practice, the Preservation and Incorporation of Valuable endoscopic Innovations (PIVI) thresholds provide the basis to be met: ≥ 90 % negative predictive value (NPV) for diagnosis of adenomatous histology and ≥ 90 % agreement on surveillance intervals. We evaluated this within the Dutch Bowel Cancer Screening Program (BCSP). Patients and methods Endoscopic and histological data were collected from participants of the national bowel cancer screening program with an unfavorable fecal immunochemical test referred for colonoscopy between February 2014 and August 2015 at four endoscopy centers. The "resect and discard" scenario was studied, resecting diminutive polyps without histological evaluation. Agreement between optical diagnosis and histological diagnosis was measured for surveillance intervals according to Dutch, European and American post-polypectomy surveillance guideline. Results Fifteen certified endoscopists participated in this study and included 3028 diminutive polyps. In 2,330 patients both optical and histological diagnosis were available. Optical diagnosis of diminutive polyps showed NPV of 84 % (95 % CI 80-87) for adenomatous histology in the rectosigmoid. Applying the 'resect and discard' strategy resulted in 90.6 %, 91.2 %, 90.9 % agreement on surveillance intervals for the Dutch, European and American guideline respectively. Conclusion Our data representing current clinical practice in the Dutch BCSP practice on optical diagnosis of diminutive polyps showed that accuracy of predicting histology remains challenging, and risk of incorrect optical diagnosis is still significant. Therefore, it is too early to safely implement these strategies.

Postponed or immediate drainage of infected necrotizing pancreatitis (POINTER trial): study protocol for a randomized controlled trial.

BACKGROUND: Infected necrosis complicates 10% of all acute pancreatitis episodes and is associated with 15-20% mortality. The current standard treatment for infected necrotizing pancreatitis is the step-up approach (catheter drainage, followed, if necessary, by minimally invasive necrosectomy). Catheter drainage is preferably postponed until the stage of walled-off necrosis, which usually takes 4 weeks. This delay stems from the time when open necrosectomy was the standard. It is unclear whether such delay is needed for catheter drainage or whether earlier intervention could actually be beneficial in the current step-up approach. The POINTER trial investigates if immediate catheter drainage in patients with infected necrotizing pancreatitis is superior to the current practice of postponed intervention. METHODS: POINTER is a randomized controlled multicenter superiority trial. All patients with necrotizing pancreatitis are screened for eligibility. In total, 104 adult patients with (suspected) infected necrotizing pancreatitis will be randomized to immediate (within 24 h) catheter drainage or current standard care involving postponed catheter drainage. Necrosectomy, if necessary, is preferably postponed until the stage of walled-off necrosis, in both treatment arms. The primary outcome is the Comprehensive Complication Index (CCI), which covers all complications between randomization and 6-month follow up. Secondary outcomes include mortality, complications, number of (repeat) interventions, hospital and intensive care unit (ICU) lengths of stay, quality-adjusted life years (QALYs) and direct and indirect costs. Standard follow-up is at 3 and 6 months after randomization. DISCUSSION: The POINTER trial investigates if immediate catheter drainage in infected necrotizing pancreatitis reduces the composite endpoint of complications, as compared with the current standard treatment strategy involving delay of intervention until the stage of walled-off necrosis. TRIAL REGISTRATION: ISRCTN, 33682933 . Registered on 6 August 2015. Retrospectively registered.

Stent-induced compression necrosis for the endoscopic removal of a partially eroded Lap-Band.

Endoscopic removal of eroded Lap-Bands is a minimally invasive alternative to surgical removal that prerequires sufficient erosion through the gastric wall, that is, ≥180° of the gastro-oesophageal wall circumference. A 69-year-old woman presented with dysphagia due to a long-standing Lap-Band erosion, currently of a 60° circumference. Adhesions due to her extensive surgical history rendered surgical treatment undesirable, so a self-expanding stent was placed endoscopically to induce sufficient erosion for subsequent endoscopic removal. During therapy, the patient complained of ructus and dysphagia, probably related to an overly proximally (oesophageal) positioned stent. After a total of 12 weeks, far longer than the described stenting duration in the literature, the Lap-Band was found free in the gastric lumen and was successfully removed using an endoscopic loop. Stent-induced compression necrosis should be considered as a minimally invasive treatment option for Lap-Bands eroded for <180°, with caution in the context of extensive fibrosis.

Incidence and Classification of Postcolonoscopy Colorectal Cancers in Inflammatory Bowel Disease: A Dutch Population-Based Cohort Study.

BACKGROUND AND AIMS: Patients with inflammatory bowel disease [IBD] colitis are at increased risk for colorectal cancer [CRC]. We examined the proportion and most likely aetiology of potentially preventable postcolonoscopy CRCs [PCCRCs] in a population-based cohort. Furthermore, adherence to IBD surveillance guidelines was evaluated in both PCCRCs and the remainder of prevalent CRCs. METHODS: All IBD patients diagnosed from 1991 to 2011 in the South Limburg region of The Netherlands [i.e. IBDSL cohort] were included. CRC cases were cross-checked with the Dutch pathology database and cancer registry. PCCRCs were defined as cancers diagnosed within 6-60 months after a colonoscopy and were classified as attributable to 'inappropriate surveillance interval', 'inadequate bowel examination', 'incomplete resection', 'missed lesion' or 'newly developed cancer'. RESULTS: Twenty CRC cases were identified during 25,931 patient years of follow-up in 2,801 patients. The proportion of PCCRCs was 45.0%. Of these, 55.6% could be considered a 'missed lesion', while other possible aetiologies occurred only once. Considering both PCCRCs [n=9] and prevalent CRCs [n=11], ten were detected after publication of the surveillance guideline, but only three patients were enrolled. Moreover, 6 CRCs [30.0%] were detected before the recommended start of surveillance. CONCLUSIONS: In the IBDSL cohort, 45.0% of all CRCs were considered to be PCCRCs, mainly classified as missed lesions. Additionally, a large proportion of CRCs in our cohort were observed before a surveillance endoscopy was performed. Therefore, stringent adherence to IBD surveillance guidelines, improving endoscopy techniques and adjusting the surveillance program may lead to a decrease in CRC incidence.

Endoscopic or surgical step-up approach for infected necrotising pancreatitis: a multicentre randomised trial.

BACKGROUND: Infected necrotising pancreatitis is a potentially lethal disease and an indication for invasive intervention. The surgical step-up approach is the standard treatment. A promising alternative is the endoscopic step-up approach. We compared both approaches to see whether the endoscopic step-up approach was superior to the surgical step-up approach in terms of clinical and economic outcomes. METHODS: In this multicentre, randomised, superiority trial, we recruited adult patients with infected necrotising pancreatitis and an indication for invasive intervention from 19 hospitals in the Netherlands. Patients were randomly assigned to either the endoscopic or the surgical step-up approach. The endoscopic approach consisted of endoscopic ultrasound-guided transluminal drainage followed, if necessary, by endoscopic necrosectomy. The surgical approach consisted of percutaneous catheter drainage followed, if necessary, by video-assisted retroperitoneal debridement. The primary endpoint was a composite of major complications or death during 6-month follow-up. Analyses were by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN09186711. FINDINGS: Between Sept 20, 2011, and Jan 29, 2015, we screened 418 patients with pancreatic or extrapancreatic necrosis, of which 98 patients were enrolled and randomly assigned to the endoscopic step-up approach (n=51) or the surgical step-up approach (n=47). The primary endpoint occurred in 22 (43%) of 51 patients in the endoscopy group and in 21 (45%) of 47 patients in the surgery group (risk ratio [RR] 0·97, 95% CI 0·62-1·51; p=0·88). Mortality did not differ between groups (nine [18%] patients in the endoscopy group vs six [13%] patients in the surgery group; RR 1·38, 95% CI 0·53-3·59, p=0·50), nor did any of the major complications included in the primary endpoint. INTERPRETATION: In patients with infected necrotising pancreatitis, the endoscopic step-up approach was not superior to the surgical step-up approach in reducing major complications or death. The rate of pancreatic fistulas and length of hospital stay were lower in the endoscopy group. The outcome of this trial will probably result in a shift to the endoscopic step-up approach as treatment preference. FUNDING: The Dutch Digestive Disease Foundation, Fonds NutsOhra, and the Netherlands Organization for Health Research and Development.

Therapeutic drug monitoring of infliximab in inflammatory bowel disease patients in a teaching hospital setting: results of a prospective cohort study.

OBJECTIVE: Therapeutic drug monitoring (TDM) of infliximab (IFX) is not routinely implemented in our clinical practice. We therefore carried out a prospective cohort study measuring IFX trough levels in our total inflammatory bowel disease (IBD) population in relation to remission. METHODS: Patient demographics, and medication and clinical history were collected from the electronic hospital information system. Blood was drawn at one time point for the determination of IFX trough levels and antibodies to IFX (ATI). Disease activity indices [Crohn's disease activity index (CDAI) and the Truelove-Witts disease activity index (TWDAI) for Crohn's disease and ulcerative colitis, respectively] and quality-of-life scores (Visual Analog Scale) were obtained. RESULTS: We included 107 patients. IFX levels varied from less than 0.02 to 21.9 µg/ml. The median IFX level was 2.8 µg/ml [interquartile range (IQR) 1.37-5.13]. The IFX level was associated significantly with remission (P=0.007). The median IFX level was 3.9 µg/ml (IQR 1.9-6.53) in patients in remission and 2.1 µg/ml in patients with active disease (IQR 0.77-4.38) (P=0.074). Receiver operating charecteristic curve analysis indicated a cutoff value of 2.18 µg/ml for CD and 6.26 µg/ml for UC. Eleven patients (10.3%) had developed ATI. The appearance of ATI was associated with the disappearance of IFX [relative risk: 2.2 (95% confidence interval: 1.368-3.610) P<0.0001], but not with relapse. The presence of ATI induced more infusion reactions [relative risk: 11.7 (95% confidence interval: 2.74-49.60) P<0.001]. CONCLUSION: TDM of IFX in IBD outpatients in a teaching hospital setting showed large interindividual differences in IFX trough levels. Despite this, we still found a significant association between remission and IFX trough levels. We determined cutoff values for both IBD modalities. IFX trough levels were not detectable in a significant proportion of IBD patients; TDM is indicated to identify this group of patients.

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].

BACKGROUND: Infected 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/DESIGN: The 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. DISCUSSION: The 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.

Increasing incidence and decreasing mortality of colorectal cancer due to marked cohort effects in southern Netherlands.

In preparation for any type of forthcoming colorectal cancer (CRC) mass screening we examined trends in CRC incidence and mortality according to sex, subsite and age in southern Netherlands. Population-based data from the Eindhoven Cancer Registry during the period 1975-2004 were used. Age-period-cohort analyses were performed to investigate possible aetiologic, diagnostic or therapeutic origins of the trends. Age-adjusted (European Standardized Rates) incidence rates for colon cancer increased since 1975 from 23 in 100 000 for both sexes to about 38 in 100 000 for males and 30 in 100 000 for females in 2004. Incidence of rectal cancer remained relatively stable at about 25 in 100 000 males and 15 in 100 000 females. The incidence of CRC increased for male patients from birth cohorts between 1900 and 1955 (P=0.010), especially in left-sided colon cancer in the younger birth cohorts [RR1900: 0.8 (95% confidence interval, CI: 0.6, 1.0), RR1960: 1.6 (95% CI: 0.9, 2.8), reference: 1910-1919]. For women a similar, although weaker increase in CRC incidence was found. Mortality rates for CRC started to decrease in 1975, more pronounced for rectal than for colon cancer. The relative risk for dying in men with CRC decreased from 1.3 (95% CI: 1.0, 1.6) in the 1900 birth cohort to 0.1 (95% CI: 0.1, 0.4) in the 1960 birth cohort, reference 1910-1919 birth cohort. The increasing incidence and decreasing mortality in CRC is largely affected by birth cohort effects. Changes in CRC incidence are likely to be attributed to lifestyle factors and decreasing mortality is due to earlier detection and improved treatment, especially among younger patients.

Improvable quality of diagnostic assessment of colorectal cancer in southern Netherlands.

OBJECTIVE: To determine the extent of guideline implementation of the diagnostic approach in patients with colorectal cancer (CRC) in southern Netherlands in 2005, with special focus on colonoscopy. METHODS: Data were extracted from the medical records for a random sample of 257 colon and 251 rectal cancer patients newly diagnosed in 2005 and recorded from the Eindhoven Cancer Registry. Adherence to guidelines was determined for diagnostic assessment. Multivariable logistic regression analysis was conducted to assess determinants of complete colonoscopy. RESULTS: Diagnostic assessment was carried out mainly by internists (50%) and gastroenterologists (36%). Colonoscopy was performed in 83% of patients with proximal/transverse colon cancer, 55% of those with distal colon cancer, and 65% of those with rectal cancer. A tumour biopsy was taken for 84% of colon and 93% of rectal tumours. Colonoscopy completeness was lower for patients with comorbidity, obstructing tumours, and patients with poor bowel preparation. Abdominal ultrasound was performed for 72% of colon and 52% of rectal cancer patients and a thoracic radiography of over 80% of CRC patients. Computed tomography (CT) of the abdomen was performed in over half of the colon cancer patients and a pelvic CT scan or magnetic resonance imaging in 36% of rectal cancer patients. CONCLUSION: Improvements in adherence to diagnostic guidelines for CRC appear possible, especially in the performance of imaging procedures. Among patients where complete visualization of the colon was not feasible with colonoscopy, imaging techniques such as virtual CT might be of added value in the near future.