Higher quality of life after metal stent placement compared with plastic stent placement for malignant extrahepatic bile duct obstruction: a randomized controlled trial.

OBJECTIVE: For palliation of extrahepatic bile duct obstruction, self-expandable metal stents (SEMS) are superior to plastic stents in terms of stent patency and occurrence of stent dysfunction. We assessed health-related quality of life (HRQoL) after stent placement to investigate whether this also results in a difference in HRQoL between patients treated with a plastic stent or SEMS. PATIENTS AND METHODS: This randomized multicenter trial included 219 patients who were randomized to receive plastic stent (n=73) or SEMS [uncovered (n=75) and covered (n=71); n=146] placement. HRQoL was assessed with two general questionnaires (EQ-5D-3L and QLQ-C30) and one disease-specific questionnaire (PAN-26). Scores were analyzed using linear mixed model regression and included all patients with baseline and at least one follow-up measurement. RESULTS: HRQoL data were available in 140 of 219 patients (64%); 71 patients (32%) declined participation and in eight patients (4%) only baseline questionnaires were available. On the QLQ-C30, the interaction between follow-up time and type of stent was significantly different on two of five functional scales [physical functioning (P=0.004) and emotional functioning (P=0.01)] in favor of patients with a SEMS. In addition, patients with SEMS reported significantly less frequent symptoms of fatigue (P=0.01), loss of appetite (P=0.02), and nausea and vomiting (0.04) over time. The EQ-VAS score decreased with time in both treatment groups, indicating a statistically significant decrease in HRQoL over time. CONCLUSION: In patients with inoperable malignant extrahepatic bile duct obstruction, SEMS placement results in better scores for general and disease-specific HRQoL over time compared with plastic stent placement.

Cost Efficacy of Metal Stents for Palliation of Extrahepatic Bile Duct Obstruction in a Randomized Controlled Trial.

BACKGROUND & AIMS: Endoscopic stents are placed for palliation of extrahepatic bile duct obstruction. Although self-expandable metal stents (SEMS) remain patent longer than plastic stents, they are more expensive. We aimed to evaluate which type of stent (plastic, uncovered SEMS [uSEMS], or partially covered SEMS [pcSEMS]) is the most effective and we assessed costs. METHODS: We performed a multicenter randomized trial in 219 patients at 18 hospitals in The Netherlands from February 2008 through February 2013. Patients were assigned randomly for placement of a plastic stent (n = 73), uSEMS (n = 75), or pcSEMS (n = 71) during endoscopic retrograde cholangiopancreatography. Patients were followed up for up to 1 year. Researchers were not blinded to groups. The main study end points included functional stent time and costs. RESULTS: The mean functional stent times were 172 days for plastic stents, 288 days for uSEMS, and 299 days for pcSEMS (P < .005 for uSEMS and pcSEMS vs plastic). The initial placement of plastic stents (€1042 or $1106) cost significantly less than placement of SEMS (€1973 or $2094) (P = .001). However, the total cost per patient at the end of the follow-up period did not differ significantly between plastic stents (€7320 or $7770) and SEMS (€6932 or $7356) (P = .61). Furthermore, in patients with short survival times (≤3 mo) or metastatic disease, the total cost per patient did not differ between plastic stents and SEMS. No differences in costs were found between pcSEMS and uSEMS. CONCLUSIONS: Although placement of SEMS (uncovered or partially covered) for palliation of extrahepatic bile duct obstruction initially is more expensive than placement of plastic stents, SEMS have longer functional time. The total costs after 1 year do not differ significantly with stent type. Dutch Clinical Trial Registration no: NTR1361.

Location in the right hemi-colon is an independent risk factor for delayed post-polypectomy hemorrhage: a multi-center case-control study.

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, P<0.001). Polyps located in the right hemi-colon had an OR of 4.67 (1.88-11.61, P=0.001) 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.

Early laparoscopic cholecystectomy improves outcomes after endoscopic sphincterotomy for choledochocystolithiasis.

BACKGROUND & AIMS: Patients with choledochocystolithiasis generally undergo endoscopic sphincterotomy (ES) followed by laparoscopic cholecystectomy (LC). However, many patients receive this surgery 6-8 weeks after ES. There is a high conversion rate of elective LC after ES, and patients can develop recurrent biliary events during the waiting period. We investigated whether the timing of surgery influences outcome. METHODS: We performed a randomized trial of patients with choledochocystolithiasis who underwent successful ES. Patients were randomly assigned to groups that received early LC (within 72 hours after ES, n = 49) or delayed LC (after 6-8 weeks, n = 47), based on an expected difference in conversion rate of 25% vs 5%, respectively. Conversion rate, biliary events during follow-up, duration and difficulty of surgeries, postoperative morbidity, and hospital stay were scored. Intention-to-treat analyses were performed. RESULTS: Groups were comparable in age, sex, and comorbidity. There was no difference between groups in conversion rate (4.3% in early vs 8.7% in delayed group) nor were there differences in operating times and/or difficulties or hospital stays. During the waiting period for LC, 17 patients in the delayed group (36.2%) developed recurrent biliary events compared with 1 patient in the early group (P < .001). CONCLUSIONS: In a randomized trial to evaluate timing of LC after ES, recurrent biliary events occurred in 36.2% of patients whose LC was delayed for 6-8 weeks. Early LC (within 72 hours) appears to be safe and might prevent the majority of biliary events in this period following sphincterotomy.

Transanal endoscopic microsurgery versus endoscopic mucosal resection for large rectal adenomas (TREND-study).

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 > or = 3 cm, located between 1-15 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.

Colonic stenting as bridge to surgery versus emergency surgery for management of acute left-sided malignant colonic obstruction: a multicenter randomized trial (Stent-in 2 study).

BACKGROUND: Acute left-sided colonic obstruction is most often caused by malignancy and the surgical treatment is associated with a high mortality and morbidity rate. Moreover, these operated patients end up with a temporary or permanent stoma. Initial insertion of an enteral stent to decompress the obstructed colon, allowing for surgery to be performed electively, is gaining popularity. In uncontrolled studies stent placement before elective surgery has been suggested to decrease mortality, morbidity and number of colostomies. However stent perforation can lead to peritoneal tumor spill, changing a potentially curable disease in an incurable one. Therefore it is of paramount importance to compare the outcomes of colonic stenting followed by elective surgery with emergency surgery for the management of acute left-sided malignant colonic obstruction in a randomized multicenter fashion. METHODS/DESIGN: Patients with acute left-sided malignant colonic obstruction eligible for this study will be randomized to either emergency surgery (current standard treatment) or colonic stenting as bridge to elective surgery. Outcome measurements are effectiveness and costs of both strategies. Effectiveness will be evaluated in terms of quality of life, morbidity and mortality. Quality of life will be measured with standardized questionnaires (EORTC QLQ-C30, EORTC QLQ-CR38, EQ-5D and EQ-VAS). Morbidity is defined as every event leading to hospital admission or prolonging hospital stay. Mortality will be analyzed as total mortality as well as procedure-related mortality. The total costs of treatment will be evaluated by counting volumes and calculating unit prices. Including 120 patients on a 1:1 basis will have 80% power to detect an effect size of 0.5 on the EORTC QLQ-C30 global health scale, using a two group t-test with a 0.05 two-sided significance level. Differences in quality of life and morbidity will be analyzed using mixed-models repeated measures analysis of variance. Mortality will be compared using Kaplan-Meier curves and log-rank statistics. DISCUSSION: The Stent-in 2 study is a randomized controlled multicenter trial that will provide evidence whether or not colonic stenting as bridge to surgery is to be performed in patients with acute left-sided colonic obstruction. TRIAL REGISTRATION: Current Controlled Trials ISRCTN46462267.

Colonization with cagA-positive Helicobacter pylori strains in intestinal metaplasia of the esophagus and the esophagogastric junction.

OBJECTIVES: Recent studies indicate that colonization with cagA-positive Helicobacter pylori (H. pylori) strains may protect against gastroesophageal reflux disease (GERD) and its complications, but the role of cagA in the etiology of Barrett's esophagus has so far been poorly investigated. The pathogenesis of intestinal metaplasia (IM) at an endoscopically normal esophagogastric junction (EGJ) is still unclear, and the role of the H. pylori virulence factor cagA in it has not been investigated. The aim of our study was to assess the relationship between H. pylori and cagA-positive H. pylori in particular and IM at an endoscopically normal EGJ and Barrett's esophagus. METHODS: Serum samples were obtained from 62 patients without IM, 43 patients with IM at an endoscopically normal junction, and 51 patients with Barrett's esophagus. IM was defined as presence of goblet cells with positive staining with Alcian blue. The prevalence of H. pylori and cagA was investigated by assessment of IgG antibody levels as determined by ELISA. RESULTS: The overall H. pylori prevalence was 59% (92/156), and the cagA prevalence was 29% (46/156). Although 63% (39/62) of IM negative subjects and 74% (32/43) of those with IM at the junction were H. pylori positive, only 41% (21/51) of Barrett's patients tested positive. The differences between the IM negative and the Barrett's group (p = 0.02) and between IM at the junction and Barrett's were significant (p = 0.002). The relative cagA prevalence (percentage with cagA positivity and H. pylori positivity) was 56% (22/39) in patients who were IM negative, 59% (19/32) in those with IM at the junction, and 24% (5/21) in those with Barrett's. The prevalence of anti-CagA was significantly lower in patients with Barrett's esophagus compared with patients who were IM negative (p = 0.002) and those who had IM at the junction (p < 0.001). No difference in cagA prevalence was seen between the latter groups. CONCLUSIONS: These findings are in line with the concept that H. pylori and cagA-positive strains in particular protect against the development of Barrett's esophagus. In contrast, our findings do not support the theory that IM at an endoscopically normal esophagogastric junction is associated with H. pylori or cagA-positive strains. IM at the junction and Barrett's esophagus seem to have different etiologies.

Prevalence of mabDAS-1 positivity in biopsy specimens from the esophagogastric junction.

OBJECTIVE: Intestinal metaplasia (IM) is a precursor for malignancies at the esophagogastric junction. A monoclonal antibody, mAbDAS-1, can probably identify cellular characteristics of IM before the appearance of goblet cells. The aim of this study was to examine the prevalence of mAbDAS-1 positivity in biopsies from the squamocolumnar junction (SCJ) and to correlate this positivity with the presence of IM and clinical findings. METHODS: In 559 patients, reflux symptoms were scored, and the presence of reflux esophagitis and hiatus hernia was evaluated during endoscopy. Two biopsy specimens were obtained from the SCJ. In a subset of patients (n = 99), biopsies from the endoscopically defined cardiac region (2 cm distal to proximal margin of gastric folds) were available. Biopsy specimens were stained with hematoxylin and eosin, Alcian Blue, modified Giemsa, and mAbDAS-1. RESULTS: mAbDAS-1 positivity was observed in the SCJ biopsies of 201 of 486 (41.4%) patients without IM and in 64 of 73 (87.7%) patients with IM. Patients without IM but with antibody positivity showed similar histological characteristics as patients with IM at the SCJ. Biopsies of 123 of 559 patients (22%) revealed a columnar-cuboidal epithelium, which was found to be mAbDAS-1 positive in 64.2% (77 of 123). Tissue specimens from the cardiac region without IM stained positive in 14.2% (13 of 91), 12 of those also stained at the SCJ. CONCLUSIONS: In patients without IM, a high prevalence of mAbDAS-1 positivity was observed. Biopsies of these patients showed similar histological characteristics as patients with IM. Although not all patients exhibiting this reactivity may develop IM, mAbDAS-1 reactivity may help in the understanding of the histogenesis of IM at the SCJ.