http://repub.eur.nl/res/aut/10807/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/32905/ 2012-07-01T00:00:00Z Background: Self-expanding metal stents (SEMSs) provide effective palliation in patients with malignant dysphagia. However, although life expectancy is generally limited, reintervention rates because of stent dysfunction are significant. New SEMSs are being designed to overcome this drawback. Objectives: To investigate whether the results of SEMS placement could be improved with a new SEMS design. Patients: Consecutive patients with dysphagia or leakage caused by malignant esophageal disease. Methods: In a multicenter randomized clinical trial, consecutive patients with dysphagia or leakage because of malignant esophageal disease were randomized to placement of a conventional stent or the new stent. Patients were followed up by scheduled telephone calls 1 and 3 months after SEMS insertion. Results: A total of 80 patients (73% male; median age, 67 years [range, 40-92 years]) were included. One patient refused follow-up. Technical success was 100% in both groups. The reintervention rate was 15/40 (38%) for the conventional stent and 4/39 (10%) for the new stent (P = .004). Major complications, including aspiration pneumonia and bleeding, occurred more frequently with the conventional stent (10/40, 25%) than with the new stent (3/39, 8%, P = .04). There was no difference in overall survival between the 2 groups. Limitations: Inclusion of patients with a perforation or fistula. Conclusions: The conventional stent and the new stent were equally effective in the relief of malignant dysphagia and sealing fistulae. The conventional stent was associated with more stent dysfunction and a significantly higher rate of major complications. Patients treated with the new stent also needed significantly fewer reinterventions than did those treated with a conventional stent. This sets the preference for the new stent over the conventional stent for patients with malignant esophageal disease. (Clinical Trial registration number: ABR27137.) http://repub.eur.nl/res/pub/25920/ 2011-07-01T00:00:00Z Background: Self-expandable metals stents (SEMSs) have increasingly been used as a temporary device to bridge chemoradiotherapy in patients with malignant esophageal disease or in patients with benign esophageal defects or stenosis. Objective: To evaluate the outcome of removal of SEMSs in a large cohort of patients with benign and malignant esophageal disease. Design: Observational study with standardized treatment and follow-up. Setting: Single university center. Patients: Between 2001 and 2010, 95 consecutive patients referred for endoscopic SEMS extraction were included. Interventions: Endoscopic stent removal. Main Outcome Measurements: Technical and functional outcome and complications. Results: A total of 124 stent extractions were undertaken in 95 patients; both partially covered (68%) and fully covered (32%) SEMSs were removed. Three patients had 2 overlapping SEMSs in place. Successful primary removal was achieved in 89%; the secondary removal rate was 96%. Uncomplicated primary removal rate was significantly higher for fully covered versus partially covered stents (P = .035) and for single versus overlapping stents (P = .033). Patients with a complicated stent removal had the stent in place significantly longer compared with patients with an uncomplicated primary stent removal (126 days vs 28 days; P = .01). Surgical removal was required in 3 patients (2.4%). Six moderate and severe complications (5%) related to the endoscopic extraction occurred. Limitations: Retrospective, nonrandomized study design. Conclusions: Primary endoscopic removal of an SEMS is feasible in the majority of patients with benign and malignant esophageal disease. A longer time that a stent is in place and the use of partially covered SEMSs both impede removal. Moreover, overlapping SEMSs should be avoided for temporary use because stent disintegration and subsequent complications may occur. http://repub.eur.nl/res/pub/33432/ 2011-06-01T00:00:00Z Objectives: Delayed hemorrhage is an infrequent, but serious complication of colonoscopic polypectomy. Large size is the only polyp-related factor that has been unequivocally proven to increase the risk of delayed bleeding. It has been suggested that location in the right hemi-colon is also a risk factor. The objective of this study was to determine whether polyp location is an independent risk factor for delayed post-polypectomy hemorrhage. Methods: A retrospective case-control study was conducted in two university hospitals and two community hospitals. Results: Thirty-nine cases and 117 controls were identified. In multivariate analysis, size and location were found to be independent polyp-related risk factors for delayed type hemorrhage. The risk increased by 13% for every 1 mm increase in polyp diameter (odds ratio (OR) 1.13, 95% confidence interval (CI) 1.05-1.20, P0.001). Polyps located in the right hemi-colon had an OR of 4.67 (1.88-11.61, P0.001) for delayed hemorrhage. Polyps in the cecum seemed to be especially at high risk in univariate analysis (OR 13.82, 95% CI 2.66-71.73), but this could not be assessed in multivariate analysis as the number of cases was too small. Polyp type (sessile or pedunculated) was not a risk factor. Conclusions: Polyp location in the right hemi-colon seems to be an independent and substantial risk factor for delayed post-polypectomy hemorrhage. A low threshold for preventive hemostatic measures is advised when removing polyps from this region. http://repub.eur.nl/res/pub/25937/ 2011-04-12T00:00:00Z Endoscopic submucosal dissection (ESD) demands a new level of endoscopic skill in Europe. A 2-day workshop was set up for trainees to carry out five ESD each in order to obtain the skill level required to perform ESD in the stomach or rectum. This study describes: (i) the workshop setup; (ii) the participant's performance; and (iii) the training effect on post-workshop clinical ESD performance. Methods: Eighteen very experienced European endoscopists participated in four half-day (4.5h) training sessions, with everybody rotating daily through six separate training stations (two each with dual, hook, or hybrid knives) with expert tutors. One anesthetized piglet was used per station and session. After 1year, the clinical ESD performance was surveyed to estimate the training effect of the workshop. Results: Overall, 74 ESD were performed, that is, 4.1 ESD per participant. On average ESD lasted 57min for 6cm2specimens. We detected a 22% rate of perforation (16 of 74 ESD with perforations), mostly attributable to participants with less experience in ESD. Those who started clinical ESD within 1year after the workshop performed 144 clinical ESD (median 8 [0-20] per trainee) mostly in the stomach (40%) and large bowel (46%) with an acceptable rate of perforation (9.7%) and surgical repair (3.5%) without mortality or persistent morbidity. Conclusion: Intense skill training for ESD is needed to reduce the risk of perforation, as demonstrated by the results of this workshop. We show that experimental ESD training, however, enables skilled European endoscopists to perform ESD in standard locations with moderate risk of perforation during the clinical learning curve. © 2011 The Authors. Digestive Endoscopy http://repub.eur.nl/res/pub/25584/ 2011-04-01T00:00:00Z Background: Several studies have evaluated predictors for complications of endoscopic retrograde cholangiopancreatography (ERCP), but their relative importance is unknown. In addition, currently used blood tests to detect post-ERCP pancreatitis are inconsistent. The aim of this study was to determine predictors of post-ERCP complications that could discriminate between patients at highest and lowest risk of post-ERCP complications and to develop a model that is able to identify patients that can safely be discharged shortly after ERCP. Methods: In a single-center, retrospective analysis over the period 2002-2007, predictors of post-ERCP complications were evaluated in a multivariable analysis and compared with those identified from a literature review. A prognostic model was developed based on these risk factors, which was further evaluated in a prospective patient population. Results: From our retrospective analysis and literature review, we selected the eight most important risk factors for post-ERCP pancreatitis and cholangitis. In the prognostic model, the risk factors (precut) sphincterotomy, sphincter of Oddi dysfunction, younger age, female gender, history of pancreatitis, pancreas divisum, and difficult cannulation accounted for a score of 1 each, whereas primary sclerosing cholangitis (PSC) accounted for a score of 2. A sum score of 4 or more in the prognostic model was associated with a high risk of developing pancreatitis and cholangitis (27%; 6/22) in the prospective patient population, whereas a sum score of 3 or less was associated with a low to intermediate risk (8%; 20/252). Conclusions: We identified specific patient- and procedure-related factors that are associated with post-ERCP complications. The prognostic model based on these factors is able to identify patients who can be safely discharged the same day after ERCP. http://repub.eur.nl/res/pub/33487/ 2011-04-01T00:00:00Z http://repub.eur.nl/res/pub/22769/ 2011-03-01T00:00:00Z Objective. Intramural hematoma of the small intestine is a complication of anticoagulant treatment with an estimated incidence of 1 case per 2500 anticoagulated patients per year. Patients may present with signs of small bowel obstruction or, in case of a ruptured hematoma, with upper gastrointestinal tract hemorrhage and hypovolemic shock. Material and methods. Case report and review of the literature. Results. We present a case of a 73-year-old male who was referred for a protruding mass in the duodenum and subsequently developed hematemesis and melena caused by a ruptured hematoma of the duodenal wall. Conclusions. Although intramural hematoma of the duodenum is a rare complication of anticoagulant therapy, early diagnosis with subsequent correction of coagulation parameters is of vital importance. http://repub.eur.nl/res/pub/33574/ 2011-01-01T00:00:00Z Background: Three different classification systems for the evaluation of Barrett's esophagus (BE) using magnification endoscopy (ME) and narrow-band imaging (NBI) have been proposed. Until now, no comparative and external evaluation of these systems in a clinical-like situation has been performed. Objective To compare and validate these 3 classification systems. Design Prospective validation study. Setting Tertiary-care referral center. Nine endoscopists with different levels of expertise from Europe and Japan participated as assessors. Patients Thirty-two patients with long-segment BE. Interventions From a group of 209 standardized prospective recordings collected on BE by using ME combined with NBI, 84 high-quality videos were randomly selected for evaluation. Histologically, 28 were classified as gastric type mucosa, 29 as specialized intestinal metaplasia (SIM), and 27 as SIM with dysplasia/cancer. Assessors were blinded to underlying histology and scored each video according to the respective classification system. Before evaluation, an educational set concerning each classification system was carefully studied. At each assessment, the same 84 videos were displayed, but in different and random order. Main Outcome Measurements Accuracy for detection of nondysplastic and dysplastic SIM. Interobserver agreement related to each classification. Results The median time for video evaluation was 25 seconds (interquartile range 20-39 seconds) and was longer with the Amsterdam classification (P < .001). In 65% to 69% of the videos, assessors described certainty about the histology prediction. The global accuracy was 46% and 47% using the Nottingham and Kansas classifications, respectively, and 51% with the Amsterdam classification. The accuracy for nondysplastic SIM identification ranged between 57% (Kansas and Nottingham) and 63% (Amsterdam). Accuracy for dysplastic tissue was 75%, irrespective of the classification system and assessor expertise level. Interobserver agreement ranged from fair (Nottingham, κ = 0.34) to moderate (Amsterdam and Kansas, κ = 0.47 and 0.44, respectively). Limitation No per-patient analysis. Conclusions All of the available classification systems could be used in a clinical-like environment, but with inadequate interobserver agreement. All classification systems based on combined ME and NBI, revealed substantial limitations in predicting nondysplastic and dysplastic BE when assessed externally. This technique cannot, as yet, replace random biopsies for histopathological analysis. http://repub.eur.nl/res/pub/32825/ 2010-12-01T00:00:00Z http://repub.eur.nl/res/pub/21928/ 2010-12-01T00:00:00Z Background: Surveillance of premalignant gastric lesions relies mainly on random biopsy sampling. Narrow band imaging (NBI) may enhance the accuracy of endoscopic surveillance of intestinal metaplasia (IM) and dysplasia. We aimed to compare the yield of NBI to white light endoscopy (WLE) in the surveillance of patients with IM and dysplasia. Methods: Patients with previously identified gastric IM or dysplasia underwent a surveillance endoscopy. Both WLE and NBI were performed in all patients during a single procedure. The sensitivity of WLE and NBI for the detection of premalignant lesions was calculated by correlating endoscopic findings to histological diagnosis. Results: Forty-three patients (28 males and 15 females, mean age 59 years) were included. IM was diagnosed in 27 patients; 20 were detected by NBI and WLE, four solely by NBI and three by random biopsies only. Dysplasia was detected in seven patients by WLE and NBI and in two patients by random biopsies only. Sixty-eight endoscopically detected lesions contained IM: 47 were detected by WLE and NBI, 21 by NBI only. Nine endoscopically detected lesions demonstrated dysplasia: eight were detected by WLE and NBI, one was detected by NBI only. The sensitivity, specificity, positive and negative predictive values for detection of premalignant lesions were 71, 58, 65 and 65% for NBI and 51, 67, 62 and 55% for WLE, respectively. Conclusions: NBI increases the diagnostic yield for detection of advanced premalignant gastric lesions compared to routine WLE. http://repub.eur.nl/res/pub/32953/ 2010-10-07T00:00:00Z Endoscopic submucosal dissection (ESD) is the gold standard technique for performing en bloc resection of large superficial tumors in the upper and lower gastrointestinal tract. Experience in Europe, however, is still limited and ESD is only performed in a few selected centers, with low volumes of cases, no description of training programs, and few published reports. In 2008, a panel of experts gathered in Rotterdam to discuss indications, training, and the wider use of ESD. The panel of experts and participants reached a consensus on five general statements: 1) ESD aims at treating mucosal cancer; 2) treatment aims for R0 resection; 3) ESD should meet quality standards; 4) ESD should be performed following national or European Society of Gastrointestinal Endoscopy (ESGE) guidelines or under institutional review board approval; and 5) ESD cases should be registered. Due to the high level of expertise needed to perform the technique safely, ESD should be performed in a step-up approach, starting with lesions presenting in the rectum or in the distal stomach, then colon, proximal stomach, and finally in the esophagus. Registration is advised either at the local site or at a national or ESGE level, and should include information on indication (Paris classification of lesion, location, and histological results prior to treatment), technique used (e.g. type of knife), results (en bloc and R0 resection), complications, and follow-up. The panel also agreed on minimal institutional requirements: good quality imaging, experienced histopathologist following the Japanese criteria (2-mm sections, micrometric invasion, vessel and lymphatic infiltration, etc), and dedicated endoscopic follow-up. Moreover, minimum training requirements were also defined: knowledge in indications and instruments, exposure to experts (currently all in Japan), hands-on experience in a model of isolated pig stomach and in live pigs, and management of complications. The experts did not reach a consensus on a minimum case load, or whether the technique should be restricted to expert centers. http://repub.eur.nl/res/pub/20527/ 2010-08-01T00:00:00Z Background: Endoscopic surveillance of pre-malignant gastric lesions may add to gastric cancer prevention. However, the appropriate biopsy regimen for optimal detection of the most advanced lesions remains to be determined. Therefore, we evaluated the yield of endoscopic surveillance by standardized and targeted biopsy protocols. Materials and Methods: In a prospective, multi-center study, patients with intestinal metaplasia (IM) or dysplasia (DYS) underwent a surveillance gastroscopy. Both targeted biopsies from macroscopic lesions and 12 non-targeted biopsies according to a standardized protocol (antrum, angulus, corpus, cardia) were obtained. Appropriate biopsy locations and the yield of targeted versus non-targeted biopsies were evaluated. Results: In total, 112 patients with IM (n = 101), or low-grade (n = 5) and high-grade DYS (n = 6) were included. Diagnosis at surveillance endoscopy was atrophic gastritis (AG) in one, IM in 77, low-grade DYS in two, high-grade DYS in three, and gastric cancer in one patient. The angulus (40%), antrum (35%) and lesser curvature of the corpus (33%) showed the highest prevalence of pre-malignant conditions. Non-targeted biopsies from the lesser curvature had a significantly higher yield as compared to the greater curvature of the corpus in diagnosing AG and IM (p =.05 and p =.03). Patients with extensive intragastric IM, which was also present at the cardia were at high risk of a concurrent diagnosis of dysplasia or gastric cancer. High-grade DYS was detected in targeted biopsies only. Conclusions: At surveillance endoscopies, both targeted and non-targeted biopsies are required for an appropriate diagnosis of (pre-)malignant gastric lesions. Non-targeted biopsies should be obtained in particular from the antrum, angulus and lesser curvature of the corpus. http://repub.eur.nl/res/pub/21194/ 2010-08-01T00:00:00Z Background: Despite advances in staging methods, surgical techniques, and adjuvant treatment, recurrent cancer after esophagectomy is a major cause of morbidity and mortality. Objective: Our purpose was to investigate the safety and efficacy of a self-expandable metal stent (SEMS) in patients with dysphagia or fistula caused by recurrent cancer after esophagectomy. Design: Prospective, observational study with standardized treatment and follow-up. Setting: Single university center. Patients: In 81 patients with recurrent cancer after previous surgical esophagectomy, 100 esophageal SEMSs were inserted for dysphagia (n = 66) or fistula formation (n = 15). Interventions: Stent placement. Main Outcome Measurements: Technical and functional outcome, complications, and survival. Results: The SEMSs restored luminal patency in 65 (98%) of 66 patients and sealed malignant fistulae in 14 (93%) of 15 patients. Stent dysfunction occurred in 24 (30%) of 81 patients. They all were successfully managed by subsequent endoscopic intervention. After stent placement, a total of 16 complications were observed. Major complications occurred in 9 (11%) of 81 patients, mild complications occurred in 7 (9%) of 81 patients. The overall 30-day mortality rate after stent insertion was 25%. Progression of the disease resulted in death after a median interval of 70 days (range 1 day to 91 months). Limitations: Nonrandomized design. Conclusions: SEMS placement in recurrent esophageal cancer after surgical resection offers adequate palliation by relieving dysphagia and sealing off esophageal respiratory fistulae. Therefore, in these patients who have a relatively short life expectancy, SEMS placement should be considered the treatment of choice. http://repub.eur.nl/res/pub/20626/ 2010-07-09T00:00:00Z Background and study aims: In patients with primary esophageal cancer, luminal patency can be restored by placement of a self-expandable metal stent (SEMS). The use of SEMS in patients with dysphagia caused by malignant extrinsic compression has largely been unreported. In this study we evaluated the efficacy of SEMS in a large cohort of patients with malignant extrinsic compression. Patients and methods: This was a prospective single-center study. Between 1995 and 2009, 50 consecutive patients with malignant extrinsic compression who had undergone SEMS placement were included (mean age 64 years; 37-males). In the majority of patients, extrinsic esophageal compression was caused by obstructive pulmonary cancer (n=23) and by mediastinal metastasis after esophagectomy for esophageal cancer (n=16). Results: Stent placement was technically successful in all patients. Severe complications occurred in 5/50 patients (10%) including perforation during dilation prior to stent insertion (n=2) and hemorrhage (n=3). Two patients (4%) died from bleeding. Mild complications were seen in 9/50 patients (18%). Recurrent dysphagia occurred in eight patients (16%) and was successfully managed by subsequent endoscopic intervention. Median survival after stent placement was 44 days (range 5 days2 years). The median stent patency of 46 days in this series exceeded median patient survival. Conclusions: Insertion of an SEMS is an effective palliative treatment for patients with dysphagia due to malignant extrinsic compression. In spite of the short survival, some patients present with recurrent dysphagia, which can be managed effectively by endoscopic re-intervention. http://repub.eur.nl/res/pub/20119/ 2010-07-01T00:00:00Z http://repub.eur.nl/res/pub/20670/ 2010-07-01T00:00:00Z OBJECTIVES: The standard approach to benign esophageal perforations consists of conservative treatment or surgery. In this study, we investigated the efficacy of short-term stent placement for nonmalignant esophageal perforations. METHODS: This is a prospective single-center study of patients with benign esophageal perforations in whom a removable self-expandable stent was placed. Data were collected from a prospective database, endoscopy records, and operation reports. To obtain follow-up data, we contacted the patients, their relatives, or their general practitioner. Results: A total of 33 patients underwent stent insertion owing to an iatrogenic perforation (n=19), Boerhaave's syndrome (n=10), or other causes (n=4); this resulted in an immediate and complete sealing of the lesion in 32 patients (97%). Stents migrated in 11 patients (33%). Four patients required an esophageal resection for failed stent therapy (n3) and failed stent removal (n1). The 90-day mortality rate was 15%. A total of 33 endoscopic stent extractions were attempted. Overall, 23 stents were extracted within 6 weeks (group I) and 10 stents between 6 and 84 weeks (group II). Extractions were uncomplicated in all patients in group I (100%) vs. in 5 patients in group II (50%) (P0.001). Six extraction-related complications occurred in group II, including two self-limiting bleedings, three stent fractures, and one impacted stent. Conclusions: In patients with a benign esophageal perforation, temporary stent therapy is effective and provides a good alternative to surgery. Complications due to stent removal can be prevented by removal of the prosthesis within 6 weeks after insertion, without compromising the efficacy of treatment. http://repub.eur.nl/res/pub/20328/ 2010-06-01T00:00:00Z Objective: To compare the sensitivity of autofluorescence endoscopy (AFE) and white light video endoscopy (WLE) for the detection of colorectal adenomas in high-risk patients belonging to Lynch syndrome (LS) or familial colorectal cancer (CRC) families. Methods: This was a prospective single-centre study carried out in a tertiary referral centre. The subjects were 75 asymptomatic patients originating from LS or familial CRC families. Patients were examined with either WLE followed by AFE or AFE followed by WLE. Back-to-back colonoscopy was performed by two blinded endoscopists. All lesions were removed during the second endoscopic procedure. Lesions missed during the second procedure were identified and removed on third pass. The sensitivity calculations for colorectal adenomas were based on histology results. The main outcome measures were the difference in sensitivity between WLE and AFE for the detection of adenomas in patients with LS or familial CRC. Results: At least one adenoma was detected in 41 (55%) patients. WLE identified adenomas in 28/41 patients and AFE in 37/41 patients, corresponding to a 32% increase. In total 95 adenomas were detected, 65 by WLE and 87 by AFE, resulting in a significantly higher sensitivity of AFE compared with WLE (92% vs 68%; p=0.001). The additionally detected adenomas with AFE were significantly smaller than the adenomas detected by WLE (mean 3.0 mm vs 4.9 mm, p<0.01). Conclusions: AFE improves the detection of colorectal adenomas in patients with LS or familial CRC. The results of this study suggest that AFE may be preferable for surveillance of these high-risk patients. http://repub.eur.nl/res/pub/26053/ 2010-06-01T00:00:00Z Background: Despite advances in training and equipment, complete colonoscopy fails, even in experienced hands, in up to 10% of cases. Double-balloon endoscopy (DBE) has been successfully used to complete colonoscopy in these patients. Single-balloon endoscopy (SBE) has become established for small-bowel enteroscopy. However, it has yet to be studied for use in colonoscopy. Objective: To assess the efficacy, performance, and safety of single-balloon colonoscopy. Design: Prospective cohort study. Setting: Academic tertiary referral center. Patients: Patients with previously failed conventional colonoscopy. Results: 23 single-balloon colonoscopy procedures were performed in 22 patients: median age 53 (range 19-75) years; 14 females, 8 males. SBE colonoscopy succeeded in cecal intubation in 22 (96%) procedures, with a median total procedure time of 30 (range 20-60) minutes. SBE colonoscopy was normal in 9 cases but resulted in a positive diagnosis in 13 (57%) procedures, including polyps (n = 6), active Crohn's disease (n = 4), Crohn's-related stricture (n = 1), and diverticulosis (n = 2). Seven (30%) procedures were therapeutic including 1 case with balloon dilation and 6 cases with polypectomy. No complications were encountered. Limitations: Limited sample size, no direct comparison with double-balloon endoscopy. Conclusions: Single-balloon-assisted colonoscopy seems a safe and effective method for completing colonoscopy in patients with previously failed or difficult colonoscopy. The outcomes are similar compared with previous studies with DBE colonoscopy in this patient group. http://repub.eur.nl/res/pub/26072/ 2010-06-01T00:00:00Z Background: The OLGA (operative link on gastritis assessment) staging system is based on severity of atrophic gastritis (AG). AG remains a difficult histopathologic diagnosis with low interobserver agreement, whereas intestinal metaplasia (IM) is associated with high interobserver agreement. Objective: The aim of this study was to evaluate whether a staging system based on IM is preferable to estimate gastric cancer risk. Design and Setting: Prospective multicenter study. Patients: A total of 125 patients previously diagnosed with gastric IM or dysplasia. Interventions: Surveillance endoscopy with extensive biopsy sampling. Main Outcome Measurements: Three pathologists graded biopsy specimens according to the Sydney classification. Interobserver agreement was analyzed by kappa statistics. In the OLGA, AG was replaced by IM, creating the OLGIM. Results: Interobserver agreement was fair for dysplasia (κ = 0.4), substantial for AG (κ = 0.6), almost perfect for IM (κ = 0.9), and improved for all stages of OLGIM compared with OLGA. Overall, 84 (67%) and 79 (63%) patients were classified as stage I-IV according to OLGA and OLGIM, respectively. Of the dysplasia patients, 5 (71%) and 6 (86%) clustered in stage III-IV of OLGA and OLGIM, respectively. Limitation: Prospective studies should confirm the correlation between gastric cancer risk and OLGIM stages. Conclusion: Replacement of AG by IM in the staging of gastritis considerably increases interobserver agreement. The correlation with the severity of gastritis remains at least as strong. Therefore, the OLGIM may be preferred over the OLGA for the prediction of gastric cancer risk in patients with premalignant lesions. http://repub.eur.nl/res/pub/19695/ 2010-05-07T00:00:00Z Background and study aim: Double-balloon enteroscopy (DBE) has proven to be a relatively safe method for small-bowel evaluation, with a complication rate of 1%. The main concern after diagnostic DBE is acute pancreatitis. Single-balloon enteroscopy (SBE) has emerged as a viable alternative to DBE. Until now, no incidence of pancreatitis has been reported for SBE. The aims were to evaluate complication rate and occurrence of hyperamylasemia and to identify the risk factors for hyperamylasemia after SBE. Patients and methods: Prospectively, consecutive patients undergoing peroral (proximal) or combined approach SBE were included. Complications were assessed at 1 and 30 days afterwards. Serum amylase and C-reactive protein (CRP) were assessed immediately before and 23 hours after SBE. Results: 166 SBE procedures were performed in 105 patients (53-male; mean age 51 years, range 987). The indications for SBE were: anemia (n=55), Crohns disease (n=31) and abdominal complaints suspicious for inflammatory bowel disease (n=5), Peutz-Jeghers syndrome (n=1) and other (n=13). Therapeutic interventions were performed during 21 procedures (13%). One perforation (1/21 therapeutic interventions, 4.8%) occurred after dilation of a benign stricture. While 13 patients (16%) had post-SBE hyperamylasemia, none had complaints suggesting acute pancreatitis. Factors such as sex, indication, procedure duration, number of passes, route of SBE, findings, and/or treatment showed no significant correlation with presence of hyperamylasemia. Conclusions: SBE appears to be a safe diagnostic endoscopic procedure. The incidence of hyperamylasemia and pancreatitis after peroral SBE seems comparable to that after DBE. http://repub.eur.nl/res/pub/27665/ 2010-05-01T00:00:00Z http://repub.eur.nl/res/pub/19558/ 2010-01-01T00:00:00Z The incidence of liposarcomas in the head and neck region is extremely low. Treatment of choice is radical surgery. However, in the head and neck region, complete eradication is not always possible. The biological indolent character of some sarcomas justify a macroscopic radical and organ-sparing technique. This article describes a patient with a liposarcoma of the upper oesophagussfincter in which a multistage flexible endoscopic debulking is performed. http://repub.eur.nl/res/pub/24829/ 2009-12-01T00:00:00Z Background: Serological screening for gastric cancer (GC) may reduce mortality. However, optimal serum markers for advanced gastric precursor lesions are lacking. Aim: To evaluate in a case-control study whether serum leptin levels correlate with intestinal metaplasia (IM) and can serve as a tool to identify patients at high risk for GC. Materials and Methods: Cases were patients with a previous diagnosis of IM or dysplasia, controls were patients without such a diagnosis. All patients underwent endoscopy. Fasting serum was collected for the measurement of leptin, pepsinogens I/II, gastrin, and Helicobacter pylori. Receiver operating characteristic (ROC) curves and their area under the curve (AUC) were provided to compare serum leptin levels with other serological markers. Results: One hundred nineteen cases and 98 controls were included. In cases, the median leptin levels were 116.6 pg/mL versus 81.9 pg/mL in controls (p =.01). After adjustment for age, sex and BMI, leptin levels remained higher in cases than in controls (p <.005). In multivariate analysis, male sex (p =.002), age (<0.001), low pepsinogen levels (p =.004) and high leptin levels (p =.04) were independent markers for the presence of IM. In addition, a ROC curve including age, sex and pepsinogen I levels had an AUC of 0.79 (95% CI (0.73-0.85)). Adding serum leptin levels increased the AUC to 0.81 (95% CI (0.75-0.86)). Conclusions: High leptin levels are associated with an increased risk of IM. Moreover, serum leptin levels are a significant independent marker for the presence of IM. However, in combination with the serological test for pepsinogen I the additional value of serum leptin levels is rather limited. http://repub.eur.nl/res/pub/17206/ 2009-10-12T00:00:00Z Background and study aim: Reported complications of double-balloon enteroscopy (DBE) include post-enteroscopy pancreatitis. Hyperamylasemia after proximal DBE is reported frequently, but the relationship to development of pancreatitis remains unclear. Hyperamylasemia may be related to balloon inflation in the pancreatic head region. The aims of the study were to identify risk factors for hyperamylasemia and to determine the incidence of hyperamylasemia and pancreatitis when a modified cautious DBE insertion protocol was used. Patients and methods: In a prospective study, involving consecutive patients undergoing a proximal DBE, serum amylase activity was assessed immediately before and after the procedure. Results: 135 patients were included (men 78, women 57; mean age 49 years [range 1788]). The mean total procedure time was 73 minutes (range 30150 minutes), and mean number of passes during the proximal DBE was 14 (624). While patients (17%) developed hyperamylasemia after the DBE procedure, only one patient with hyperamylasemia had clinical symptoms indicating a mild acute pancreatitis (0.7%). Total procedure time and number of passes correlated significantly with the occurrence of hyperamylasemia. Conclusions: We found a low incidence of hyperamylasemia and pancreatitis post-DBE. Theoretically, this could result from the modified insertion technique, with local strain and friction of the small bowel as remaining causes of hyperamylasemia, a notion supported by the significant relation between hyperamylasemia and duration of DBE and total number of passes. We therefore advise use of the cautious insertion technique and, if possible, reduction of duration and of number of passes in every proximal DBE. http://repub.eur.nl/res/pub/24371/ 2009-07-01T00:00:00Z Background: Current investigations into endoscopic screening for the early detection of Barrett's esophageal adenocarcinoma have focused on visualization of the microvascular morphology by using narrow-band imaging (NBI). Adjustment of the center wavelength, particularly of the NBI blue imaging filter, may lead to improved image contrast, depending on the oxygen saturation of the microvascular blood of dysplastic and early cancerous Barrett's mucosa. Objective: To perform in vivo, noninvasive measurements of the oxygen saturation of the microvascular blood for different pathologic grades of Barrett's mucosa by using differential path-length spectroscopy (DPS). Design: DPS measurements were made on normal (n = 7), low-grade dysplastic (n = 10), high-grade dysplastic (n = 7), and cancerous (n = 4) Barrett's mucosa by using a fiber-optic probe, and were correlated to the histologic outcome of biopsy specimens taken from the same location. Setting: Academic medical center. Patients: Fifteen patients with Barrett's esophagus who were undergoing gastroscopy. Interventions: Biopsy specimens were taken from suspicious areas in the esophagus. Main Outcome Measurements: The oxygen saturation of the microvascular blood of different pathologic grades of Barrett's mucosa was assessed. Results: The oxygen saturation of the microvascular blood remains high (approximately 90%) throughout the metaplasia-dysplasia-adenocarcinoma sequence. Limitation: The small number of patients. Conclusions: The current NBI blue imaging filter, centered on the peak absorption of oxyhemoglobin (415 nm), is well chosen, and little improvement in image contrast is to be expected from changes in this center wavelength. http://repub.eur.nl/res/pub/24373/ 2009-07-01T00:00:00Z Background: Surveillance of intestinal metaplasia (IM) of the gastric mucosa should be limited to patients at high risk of gastric cancer. Patients with extensive IM are at increased cancer risk; however, the intragastric extent of IM is usually unknown at the time of the initial diagnosis. Objective: To assess the predictive value of clinical, histologic, and serologic parameters for the intragastric extent of IM. Design and Setting: Prospective, multicenter study. Patients: Eighty-eight patients with a previous diagnosis of IM of the gastric mucosa. Intervention: Surveillance gastroscopy with extensive random biopsy sampling. Main Outcome Measurements: Biopsy specimens were evaluated according to the Sydney classification system. In addition, serologic testing of Helicobacter pylori and cagA status, pepsinogens I and II, gastrin, and intrinsic factor antibodies was performed. The association between the available parameters and extensive IM was evaluated with logistic regression analysis. Results: In 51 patients (58%), IM was present in the biopsy specimens from at least 2 intragastric locations. The most important predictors of extensive IM were a family history of gastric cancer, alcohol use ≥1 unit/d (1 glass, approximately 10 mL or 8 g ethanol), moderate or marked IM of the index biopsy specimen, and a pepsinogen I to II ratio <3.0. A simple risk score based on these factors could identify extensive IM in 24 of 25 patients (sensitivity 96%). Limitation: A prospective cohort study should confirm the proposed risk stratification. Conclusions: A risk score of clinical, histologic, and serologic parameters can predict extensive intragastric IM and may serve as a practical tool to select patients for surveillance endoscopy in routine clinical practice. http://repub.eur.nl/res/pub/24957/ 2009-04-13T00:00:00Z Background: Recent non-randomized studies suggest that extended endoscopic mucosal resection (EMR) is equally effective in removing large rectal adenomas as transanal endoscopic microsurgery (TEM). If equally effective, EMR might be a more cost-effective approach as this strategy does not require expensive equipment, general anesthesia and hospital admission. Furthermore, EMR appears to be associated with fewer complications. The aim of this study is to compare the cost-effectiveness and cost-utility of TEM and EMR for the resection of large rectal adenomas. Methods/design. Multicenter randomized trial among 15 hospitals in the Netherlands. Patients with a rectal adenoma 3 cm, located between 115 cm ab ano, will be randomized to a TEM- or EMR-treatment strategy. For TEM, patients will be treated under general anesthesia, adenomas will be dissected en-bloc by a full-thickness excision, and patients will be admitted to the hospital. For EMR, no or conscious sedation is used, lesions will be resected through the submucosal plane in a piecemeal fashion, and patients will be discharged from the hospital. Residual adenoma that is visible during the first surveillance endoscopy at 3 months will be removed endoscopically in both treatment strategies and is considered as part of the primary treatment. Primary outcome measure is the proportion of patients with recurrence after 3 months. Secondary outcome measures are: 2) number of days not spent in hospital from initial treatment until 2 years afterwards; 3) major and minor morbidity; 4) disease specific and general quality of life; 5) anorectal function; 6) health care utilization and costs. A cost-effectiveness and cost-utility analysis of EMR against TEM for large rectal adenomas will be performed from a societal perspective with respectively the costs per recurrence free patient and the cost per quality adjusted life year as outcome measures. Based on comparable recurrence rates for TEM and EMR of 3.3% and considering an upper-limit of 10% for EMR to be non-inferior (beta-error 0.2 and one-sided alpha-error 0.05), 89 patients are needed per group. Discussion. The TREND study is the first randomized trial evaluating whether TEM or EMR is more cost-effective for the treatment of large rectal adenomas. Trial registration number. (trialregister.nl) NTR1422. http://repub.eur.nl/res/pub/29191/ 2008-11-01T00:00:00Z Histopathologic grading of dysplasia in Barrett esophagus (BE) shows substantial interobserver and intraobserver variation. We used immunohistochemical analysis with a set of tumor cell markers, ie, epidermal growth factor receptor (EGFR), ERBB2 (HER2/neu), MYC, CDKN2A (p16), SMAD4, MET, CCND1 (cyclin D1), CTNNB1 (β-catenin), and TP53 (p53), in histologic sections of endoscopic biopsies of 86 patients with BE in various stages of neoplastic progression. The markers, except SMAD4, were scored as 0 (<1% of cells stained), 1 (1%-25%), 2 (26%-50%), or 3 (>50%). All markers, except EGFR, showed a significant trend for immunohistochemical protein overexpression during malignant progression in BE (P < .01). When the successive stages along the metaplasia-low-grade dysplasia (LGD)-high-grade dysplasia (HGD)-adenocarcinoma axis were compared, protein overexpression of β-catenin separated LGD from metaplasia, whereas protein overexpression of cyclin D1 and p53 discriminated HGD from LGD (all P < .001). β-Catenin can be helpful for a diagnosis of LGD in BE, although it stains positively in a subset only, whereas p53 remains an appropriate marker to define HGD. In case of doubt, cyclin D1 can be added to separate LGD from HGD in BE. http://repub.eur.nl/res/pub/15205/ 2008-09-01T00:00:00Z Background and study aims: Simulators are increasingly used in skills training for physicians; however data on systematic evaluation of the performance of these simulators are scarce compared with those used in aviation. The objectives of this study were to determine the expert validity, the construct validity, and the training value of the novel Olympus simulator as judged by experts. Patients and methods: Participants were novices and experts. Novices had no prior experience in flexible endoscopy; experts had all performed more than 1000 colonoscopies. Participants filled out a questionnaire on their impression of the realism of the colonoscopy exercises performed. These included a dexterity exercise and a virtual colonoscopy. Test parameters used were points acquired in a game, time to reach the cecum, maximum insertion force, and "patient pain." Results: Novices (n=26) scored a median of 973 points (range -118-1393), experts (n=23) scored 1212 points (range 89-1375). This difference did not reach significance (P= 0.073). Experts performed virtual colonoscopy significantly faster than novices (220 vs. 780 s, P < 0.001) but used more insertion force (11.8 vs. 11.6 N; P= 0.147). Maximum pain score was higher in the expert group: 86% vs. 73%. (P= 0.018). The realism was graded 6.5 on a 10-point scale. Experts considered the Olympus simulator beneficial for the training of novice endoscopists. Conclusions: The novel Olympus simulator discriminates excellently between the measured levels of expertise. The prototype offers a good realistic representation of colonoscopy according to experts. Although the software development is continuing, the device can already be implemented in the training program of novice endoscopists. http://repub.eur.nl/res/pub/35065/ 2007-12-01T00:00:00Z http://repub.eur.nl/res/pub/35313/ 2007-07-12T00:00:00Z Objective. Patients with Barrett's esophagus (BE) are at risk of developing esophageal adenocarcinoma, which is usually preceded by dysplastic changes of the metaplastic mucosa. The aim of this study was to increase the understanding of the development of dysplastic lesions in BE through the identification of genes that are differentially transcribed in these tissue types. Material and methods. Paired biopsy samples from non-dysplastic BE, and high-grade dysplasia from a single patient were used for histological evaluation and gene expression profile analysis. In addition, relative mRNA levels of differentially expressed genes were tested to validate the association with the presence or absence of dysplasia by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) (58 biopsy samples containing squamous epithelium, non-dysplastic BE, high-grade dysplasia, or adenocarcinoma from 23 unrelated patients) and immunohistochemistry (9 sets of paired non-dysplastic/high-grade dysplasiac samples from 9 unrelated patients). Results. Microarray results from high-grade dysplasia showed 866 genes with a>2-fold difference in mRNA levels compared with non-dysplastic BE. Subsequent comparison of mRNA levels of the 22 genes with a>10-fold difference in 76 unrelated biopsies showed that only two of these genes, i.e. calgranulin A (S100A8; p=0.017) and calgranulin B (S100A9; p=0.022), were consistently up-regulated in high-grade dysplasia, as were protein levels for calgranulin A and B. Conclusions. This is the first report of an association between the calprotectin complex, which is involved in chemotaxis of neutrophils, and the progression towards high-grade dysplasia in BE. It remains to be established whether differentially expressed proteins in biopsies form BE can be used to facilitate the diagnosis of advanced dysplasia in BE. http://repub.eur.nl/res/pub/35336/ 2007-07-01T00:00:00Z Background and study aims: Double balloon enteroscopy (DBE) is a new technique for the visualization of the small bowel. Although the technique is widely used, little is known about the complications. A few complications have been reported in the literature, mainly in case reports. The aim of this study was to establish the complication rate of both diagnostic and therapeutic DBE. Patients and methods: A total of 10 centers (nine academic centers and one teaching hospital) across four continents participated in the study. Complications were defined according to the literature. A therapeutic DBE was defined as a DBE with use of argon plasma coagulation, a polypectomy snare, injection of fluids (other than ink for marking), removal of foreign body, or balloon dilation. Results: A total 85 adverse events were reported in 2362 DBE procedures. In all, 40 events fulfilled the definition of a complication, 13 in 1728 diagnostic DBE (0.8%) and 27 during 634 therapeutic procedures (4.3 %). The complications were rated minor in 21 (0.9 %), moderate in 6 (0.3 %) and severe in 13 procedures (0.6%). No fatal complications were reported. Seven cases of pancreatitis were reported, six after diagnostic (0.3 %) and one after therapeutic (0.2 %) DBE. Conclusions: Diagnostic DBE is safe with a low complication rate. The complication rate of therapeutic DBE is high compared with therapeutic colonoscopy. The reason for this is unclear. The incidence of pancreatitis after DBE is low (0.3 %), but has to be considered in patients with persistent abdominal complaints after a DBE procedure. http://repub.eur.nl/res/pub/36703/ 2007-02-01T00:00:00Z Gastric cancer is an important worldwide health problem and causes considerable morbidity and mortality. It represents the second leading cause of cancer-related death worldwide. A cascade of recognizable precursor lesions precedes most distal gastric carcinomas. In this multistep model of gastric carcinogenesis, Helicobacter pylori causes chronic active inflammation of the gastric mucosa, which slowly progresses through the premalignant stages of atrophic gastritis, intestinal metaplasia and dysplasia to gastric carcinoma. Detection and treatment of premalignant lesions may thus provide a basis for gastric cancer prevention. However, at present, premalignant changes of the gastric mucosa are frequently disregarded in clinical practice or result in widely varying follow-up frequency or treatment. This review provides an overview of current knowledge on detection, surveillance and treatment of patients with premalignant gastric lesions, and identifies the uncertainties that require further research. http://repub.eur.nl/res/pub/8296/ 2004-01-01T00:00:00Z BACKGROUND: Photochemical and thermal methods are used for ablating Barrett's oesophagus (BO). The aim of this study was to compare 5-aminolevulinic acid induced photodynamic therapy (ALA-PDT) with argon plasma coagulation (APC) with respect to complete reversal of BO. METHODS: Patients with BO (32 no dysplasia and eight low grade dysplasia) were randomised to one of three treatments: (a) ALA-PDT as a single dose of 100 J/cm(2) at four hours (PDT100; n = 13); (b) ALA-PDT as a fractionated dose of 20 and 100 J/cm(2) at one and four hours, respectively (PDT20+100; n = 13); or (c) APC at a power setting of 65 W in two sessions (APC; n = 14). If complete elimination of BO was not achieved by the designated treatment, the remaining BO was treated by a maximum of two sessions of APC. RESULTS: Mean endoscopic reduction of BO at six weeks was 51% (range 20-100%) in the PDT100 group, 86% (range 0-100%) in the PDT20+100 group, and 93% (range 40-100%) in the APC group (PDT100 v PDT20+100, p<0.005; PDT100 v APC, p<0.005; and PDT20+100 v APC, NS) with histologically complete ablation in 1/13 (8%) patients in the PDT100 group, 4/12 (33%) in the PDT20+100 group, and 5/14 (36%) in the APC group (NS). Remaining BO was additionally treated with APC in 23/40 (58%) patients. Histological examination at 12 months revealed complete ablation in 9/11 (82%) patients in the PDT100 group, in 9/10 (90%) patients in the PDT20+100 group, and in 8/12 (67%) patients in the APC group (NS). At 12 months, no dysplasia was detected. Side effects (that is, pain (p<0.01), and nausea and vomiting (p<0.05)) and elevated liver transaminases (p<0.01) were more common after PDT than APC therapy. One patient died three days after treatment with PDT, presumably from cardiac arrhythmia. CONCLUSION: APC alone or ALA-PDT in combination with APC can lead to complete reversal of Barrett's epithelium in at least two thirds of patients when administered in multiple treatment sessions. As the goal of treatment should be complete reversal of Barrett's epithelium, we do not recommend these techniques for the prophylactic ablation of BO. http://repub.eur.nl/res/pub/8369/ 2004-01-01T00:00:00Z BACKGROUND: In Barrett's oesophagus (BO), squamous epithelium is replaced by specialised intestinal epithelium (SIE). Transcription factors associated with intestinal differentiation, such as CDX2, may be involved in BO development. AIM: To investigate CDX2 expression in BO, squamous epithelium, and oesophageal adenocarcinoma (ADC). METHODS: CDX2 expression was assessed in 245 samples-167 biopsies of the columnar lined segment and 38 squamous epithelial biopsies of 39 patients with histologically confirmed BO (10 with ADC). Forty biopsies from 20 patients with reflux oesophagitis (RO) without BO were also evaluated. CDX2 protein was investigated immunohistochemically in 138 biopsies from 16 patients with BO, four with ADC, and 20 with RO. Cdx2 and Muc2 mRNA were detected semiquantitatively using 88 BO biopsies and squamous epithelium from 19 BO patients, and when present from ADC. RESULTS: SIE was present in 53/79 biopsies from the columnar lined segment; CDX2 protein was seen in all epithelial cells, but not in biopsies containing only gastric metaplastic epithelium (26/79), or in squamous epithelium (0/40) of patients with RO. Cdx2 mRNA was detected in all biopsies with goblet cell specific Muc2 transcription-indicative of SIE. Low Cdx2 mRNA expression was seen in 6/19 squamous epithelium samples taken 5 cm above the squamocolumnar junction of BO patients. CONCLUSION: CDX2 protein/mRNA is strongly associated with oesophageal SIE. Cdx2 mRNA was present in the normal appearing squamous epithelium of one third of BO patients, and may precede morphological changes seen in BO. Therefore, pathways that induce Cdx2 transcription in squamous epithelial cells may be important in BO development. http://repub.eur.nl/res/pub/8370/ 2004-01-01T00:00:00Z BACKGROUND: Patients with Barrett's oesophagus (BO) are at risk of oesophageal adenocarcinoma. Because the pattern of mucosal mucins changes during neoplastic progression, it may serve as a marker of intraepithelial neoplasia. AIMS: To determine the expression pattern of mucins in neoplastic BO epithelium (high grade dysplasia) and correlate it with the expression of apoptosis markers Bax and Bcl-2. METHODS: Thirty seven patients with BO were studied: 16 without intraepithelial neoplasia, six with high grade intraepithelial neoplasia (HGN), and 15 with infiltrating adenocarcinoma. Biopsies were obtained from squamous epithelium, Barrett's epithelium, and (when present) foci of suspected HGN or adenocarcinoma. MUC1-4, MUC5AC, MUC5B, MUC6, Bax, and Bcl-2 mRNA were determined by semiquantitative RT-PCR. MUC2, MUC5AC, and MUC6 protein was determined by immunoblotting. RESULTS: Mucin expression varied between neoplastic progression stages in BO. Mucin mRNA levels were low in squamous epithelium, except for MUC4, and were at least four times higher in BO and HGN (p<0.001), but less so in adenocarcinoma. MUC4 expression was significantly lower in BO than in normal squamous epithelium, whereas in HGN and adenocarcinoma, levels were significantly higher than in BO (p = 0.037). The Bax:Bcl-2 ratio was increased in HGN compared with BO (p = 0.04). MUC2, MUC5AC, and MUC6 protein values correlated with mRNA data. CONCLUSIONS: Mucin expression varies during the development of oesophageal adenocarcinoma in BO. MUC4 could serve as a tumour marker in this process. In contrast to animal studies, upregulation of MUC4 in HGN is associated with increased apoptosis, suggesting that MUC4 plays a minor role in apoptosis regulation in BO.