Pieter Scholten

Low-Grade Dysplasia in Barrett's Esophagus: Overdiagnosed and Underestimated

OBJECTIVES:Published data on the natural history of low-grade dysplasia (LGD) in Barretts esophagus (BE) are inconsistent and difficult to interpret. We investigated the natural history of LGD in a large community-based cohort of BE patients after reviewing the original histological diagnosis by an expert panel of pathologists.METHODS:Histopathology reports of all patients diagnosed with LGD between 2000 and 2006 in six non-university hospitals were reviewed by two expert pathologists. This panel diagnosis was subsequently compared with the histological outcome during prospective endoscopic follow-up.RESULTS:A diagnosis of LGD was made in 147 patients. After pathology review, 85% of the patients were downstaged to non-dysplastic BE (NDBE) or to indefinite for dysplasia. In only 15% of the patients was the initial diagnosis LGD. Endoscopic follow-up was carried out in 83.6% of patients, with a mean follow-up of 51.1 months. For patients with a consensus diagnosis of LGD, the cumulative risk of progressing to high-grade dysplasia or carcinoma (HGD or Ca) was 85.0% in 109.1 months compared with 4.6% in 107.4 months for patients downstaged to NDBE (P<0.0001). The incidence rate of HGD or Ca was 13.4% per patient per year for patients in whom the diagnosis of LGD was confirmed. For patients downstaged to NDBE, the corresponding incidence rate was 0.49%.CONCLUSIONS:LGD in BE is an overdiagnosed and yet underestimated entity in general practice. Patients diagnosed with LGD should undergo an expert pathology review to purify this group. In case the diagnosis of LGD is confirmed, patients should undergo strict endoscopic follow-up or should be considered for endoscopic ablation therapy.

Endoscopic trimodal imaging versus standard video endoscopy for detection of early Barrett's neoplasia: a multicenter, randomized, crossover study in general practice

BACKGROUND Endoscopic trimodal imaging (ETMI) may improve detection of early neoplasia in Barretts esophagus (BE). Studies with ETMI so far have been performed in tertiary referral settings only. OBJECTIVE To compare ETMI with standard video endoscopy (SVE) for the detection of neoplasia in BE patients with an intermediate-risk profile. DESIGN Multicenter, randomized, crossover study. SETTING Community practice. PATIENTS AND METHODS BE patients with confirmed low-grade intraepithelial neoplasia (LGIN) underwent both ETMI and SVE in random order (interval 6-16 weeks). During ETMI, BE was inspected with high-resolution endoscopy followed by autofluorescence imaging (AFI). All visible lesions were then inspected with narrow-band imaging. During ETMI and SVE, visible lesions were sampled followed by 4-quadrant random biopsies every 2 cm. MAIN OUTCOME MEASUREMENTS Overall histological yield of ETMI and SVE and targeted histological yield of ETMI and SVE. RESULTS A total of 99 patients (79 men, 63±10 years) underwent both procedures. ETMI had a significantly higher targeted histological yield because of additional detection of 22 lesions with LGIN/high-grade intraepithelial neoplasia (HGIN)/carcinoma (Ca) by AFI. There was no significant difference in the overall histological yield (targeted+random) between ETMI and SVE. HGIN/Ca was diagnosed only by random biopsies in 6 of 24 patients and 7 of 24 patients, with ETMI and SVE, respectively. LIMITATIONS Inspection, with high-resolution endoscopy and AFI, was performed sequentially. CONCLUSION ETMI performed in a community-based setting did not improve the overall detection of dysplasia compared with SVE. The diagnosis of dysplasia is still being made in a significant number of patients by random biopsies. Patients with a confirmed diagnosis of LGIN have a significant risk of HGIN/Ca. ( CLINICAL TRIAL REGISTRATION NUMBER ISRCTN91816824; NTR867.).

Endoscopic trimodal imaging detects colonic neoplasia as well as standard video endoscopy.

BACKGROUND & AIMS Endoscopic trimodal imaging (ETMI) is a novel endoscopic technique that combines high-resolution endoscopy (HRE), autofluorescence imaging (AFI), and narrow-band imaging (NBI) that has only been studied in academic settings. We performed a randomized, controlled trial in a nonacademic setting to compare ETMI with standard video endoscopy (SVE) in the detection and differentiation of colorectal lesions. METHODS The study included 234 patients scheduled to receive colonoscopy who were randomly assigned to undergo a colonoscopy in tandem with either ETMI or SVE. In the ETMI group (n=118), first examination was performed using HRE, followed by AFI. In the other group, both examinations were performed using SVE (n=116). In the ETMI group, detected lesions were differentiated using AFI and NBI. RESULTS In the ETMI group, 87 adenomas were detected in the first examination (with HRE), and then 34 adenomas were detected during second inspection (with AFI). In the SVE group, 79 adenomas were detected during the first inspection, and then 33 adenomas were detected during the second inspection. Adenoma detection rates did not differ significantly between the 2 groups (ETMI: 1.03 vs SVE: 0.97, P=.360). The adenoma miss-rate was 29% for HRE and 28% for SVE. The sensitivity, specificity, and accuracy of NBI in differentiating adenomas from nonadenomatous lesions were 87%, 63%, and 75%, respectively; corresponding values for AFI were 90%, 37%, and 62%, respectively. CONCLUSIONS In a nonacademic setting, ETMI did not improve the detection rate for adenomas compared with SVE. NBI and AFI each differentiated colonic lesions with high levels of sensitivity but low levels of specificity.

Percutaneous endoscopic gastrostomy: Complications and suggestions to avoid them

Objectives Percutaneous endoscopic gastrostomy (PEG) tubes have become an excellent alternative for the long-term management of patients with proximal obstructions of the gastrointestinal tract. However, their use has limitations and can be associated with serious complications. We therefore studied the frequency and severity of complications related to the use of PEG tubes in our clinic. Design All adults (aged 18 years and above) in whom a PEG tube was placed between January 1 1994 and January 1 1999 at the Free University Hospital in Amsterdam were included in this study. In initial cases, the indication and procedure were individually judged according to a liberal protocol. However, after several major complications, a strict procedure protocol was implemented in September 1996. Results During the study period, 263 PEG tubes were placed in 254 patients with head and neck cancer (n = 183; 70%), neurological disorders (n = 52; 20%) or severe upper gastrointestinal motility disorders (n = 28; 11%). In period I, 167 PEG tubes were placed and in period II, 96 PEG tubes were inserted. Patients were followed for a median 111 days. Minor complications occurred in 13% of the patients. Major complications occurred in 8% of the patients. In period I, the percentage of major complications was higher than in period II (9.5% versus 6%). Conclusion PEG tube placement is a safe procedure when performed according to strict guidelines. By doing so, PEG tubes allow optimal feeding for prolonged periods with the occasional need for replacement of the tube. PEG tubes should not be introduced in acutely ill patients, patients with a short life expectancy and preferably not to patients with severe coughing.

Covered transjugular intrahepatic portosystemic shunt versus endoscopic therapy + β‐blocker for prevention of variceal rebleeding

Gastroesophageal variceal bleeding in patients with cirrhosis is associated with significant morbidity and mortality, as well as a high rebleeding risk. Limited data are available on the role of transjugular intrahepatic portosystemic shunt (TIPS) with covered stents in patients receiving standard endoscopic, vasoactive, and antibiotic treatment. In this multicenter randomized trial, long‐term endoscopic variceal ligation (EVL) or glue injection + β‐blocker treatment was compared with TIPS placement in 72 patients with a first or second episode of gastric and/or esophageal variceal bleeding, after hemodynamic stabilization upon endoscopic, vasoactive, and antibiotic treatment. Randomization was stratified according to Child‐Pugh score. Kaplan‐Meier (event‐free) survival estimates were used for the endpoints rebleeding, death, treatment failure, and hepatic encephalopathy. During a median follow‐up of 23 months, 10 (29%) of 35 patients in the endoscopy + β‐blocker group, as compared to 0 of 37 (0%) patients in the TIPS group, developed variceal rebleeding (P = 0.001). Mortality (TIPS 32% vs. endoscopy 26%; P = 0.418) and treatment failure (TIPS 38% vs. endoscopy 34%; P = 0.685) did not differ between groups. Early hepatic encephalopathy (within 1 year) was significantly more frequent in the TIPS group (35% vs. 14%; P = 0.035), but during long‐term follow‐up this difference diminished (38% vs. 23%; P = 0.121). Conclusions: In unselected patients with cirrhosis, who underwent successful endoscopic hemostasis for variceal bleeding, covered TIPS was superior to EVL + β‐blocker for reduction of variceal rebleeding, but did not improve survival. TIPS was associated with higher rates of early hepatic encephalopathy. (Hepatology 2016;63:581–589)

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)

BackgroundAcute 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/designPatients 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.DiscussionThe 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 registrationCurrent Controlled Trials ISRCTN46462267.

Covered TIPS vs endoscopic therapy + Β‐blocker for prevention of variceal rebleeding

Gastroesophageal variceal bleeding in patients with cirrhosis is associated with significant morbidity and mortality, as well as a high rebleeding risk. Limited data are available on the role of transjugular intrahepatic portosystemic shunt (TIPS) with covered stents in patients receiving standard endoscopic, vasoactive, and antibiotic treatment. In this multicenter randomized trial, long‐term endoscopic variceal ligation (EVL) or glue injection + β‐blocker treatment was compared with TIPS placement in 72 patients with a first or second episode of gastric and/or esophageal variceal bleeding, after hemodynamic stabilization upon endoscopic, vasoactive, and antibiotic treatment. Randomization was stratified according to Child‐Pugh score. Kaplan‐Meier (event‐free) survival estimates were used for the endpoints rebleeding, death, treatment failure, and hepatic encephalopathy. During a median follow‐up of 23 months, 10 (29%) of 35 patients in the endoscopy + β‐blocker group, as compared to 0 of 37 (0%) patients in the TIPS group, developed variceal rebleeding (P = 0.001). Mortality (TIPS 32% vs. endoscopy 26%; P = 0.418) and treatment failure (TIPS 38% vs. endoscopy 34%; P = 0.685) did not differ between groups. Early hepatic encephalopathy (within 1 year) was significantly more frequent in the TIPS group (35% vs. 14%; P = 0.035), but during long‐term follow‐up this difference diminished (38% vs. 23%; P = 0.121). Conclusions: In unselected patients with cirrhosis, who underwent successful endoscopic hemostasis for variceal bleeding, covered TIPS was superior to EVL + β‐blocker for reduction of variceal rebleeding, but did not improve survival. TIPS was associated with higher rates of early hepatic encephalopathy. (Hepatology 2016;63:581–589)

Long-term risk of oesophagitis, Barrett's oesophagus and oesophageal cancer in achalasia patients

Achalasia is a motility disorder of the oesophagus of unknown origin in which loss of relaxation of the lower oesophageal sphincter (LOS) and aperistalsis in the distal oesophagus leads to functional oesophageal obstruction. The treatment is symptomatic, aimed at lowering of the LOS pressure, and may be accompanied by various side effects, including gastro-oesophageal reflux, a risk factor for oesophagitis and its complications. Stasis and fermentation can also lead to inflammation of the oesophageal mucosa, giving rise to hyperplasia of the epithelium, multifocal dysplasia and in some patients eventually squamous cell carcinoma. Unfortunately, the sensitivity and specificity of endoscopical inspection to assess inflammation or dysplasia of the oesophageal lining is low, such that biopsy sampling is necessary for accurate assessment. Although it is generally accepted that achalasia is a pre-malignant disorder, the reported increased risk of patients with achalasia developing a squamous cell carcinoma varies from 0 to 140 times that of the normal population. In addition, achalasia may predispose to Barretts metaplasia and oesophageal adenocarcinoma, which have been described in case reports after myotomy. Surveillance endoscopy with tissue sampling to detect pre-neoplastic lesions has been recommended, even though this can be very difficult due to mucosal adherence of food as well as hyperplastic changes of the mucosa. In the event of moderate to severe inflammation and/or persisting stasis of food despite adequate LOS pressure-lowering therapy, the surveillance interval should be shortened and performed after a 3-day liquid diet. The exact technique and time intervals still need to be established, however.

Is esophagogastroduodenoscopy before Roux-en-Y gastric bypass or sleeve gastrectomy mandatory?

BACKGROUND Roux-Y Gastric Bypass is a frequently used technique in bariatric surgery. Postoperative anatomy is altered by exclusion of the stomach, which makes this organ inaccessible for future esophagogastroduodenoscopy (EGD). The value of preoperative assessment of the stomach is unclear. Some institutions choose to investigate the future remnant stomach by EGD, others do not. Aim of the present study is to quantify the yield of preoperative EGD in our institution. METHODS Patients, planned for primary laparoscopic Roux-Y Gastric Bypass (LRYGB) or laparoscopic sleeve gastrectomy from December 2007 until August 2012, were screened by EGD in advance. Results of EGD and patient characteristics were retrospectively analyzed and categorized according to a classification system based on intervention needed. RESULTS 523 patients (122 male, 401 female, mean age 44.3 years, average BMI 46.6) underwent preoperative EGD. In 257 patients (48.9%) no abnormality was found (group A), 117 patients (17.2%) had abnormalities without treatment consequences (B1), 84 patients (of the 326 tested [comment #1, reviewer #1, 26.8%] were H. Pylori positive (B2), in 75 (14.3%) treatment with proton pump inhibitors was required (B3), 6 (1.1%) required follow up EGD before surgery (C). For1 patient (0.2%) the operation was canceled because preoperative EGD presented with Barretts esophagus with carcinoma (D). When all abnormalities were taken into account, baselines did show a significant difference for age, gender and reflux symptoms. CONCLUSION Standard preoperative assessment by EGD in patients who are planned for bariatric surgery is not indicated. The number needed to screen to find clinically significant abnormalities is high.

Hemorrhoids detected at colonoscopy: an infrequent cause of false-positive fecal immunochemical test results

BACKGROUND Colorectal cancer screening by fecal immunochemical tests (FITs) is hampered by frequent false-positive (FP) results and thereby the risk of complications and strain on colonoscopy capacity. Hemorrhoids might be a plausible cause of FP results. OBJECTIVE To determine the contribution of hemorrhoids to the frequency of FP FIT results. DESIGN Retrospective analysis from prospective cohort study. SETTING Five large teaching hospitals, including 1 academic hospital. PATIENTS All subjects scheduled for elective colonoscopy. INTERVENTIONS FIT before bowel preparation. MAIN OUTCOME MEASUREMENTS Frequency of FP FIT results in subjects with hemorrhoids as the only relevant abnormality compared with FP FIT results in subjects with no relevant abnormalities. Logistic regression analysis to determine colonic abnormalities influencing FP results. RESULTS In 2855 patients, 434 had positive FIT results: 213 had advanced neoplasia and 221 had FP results. In 9 individuals (4.1%; 95% CI, 1.4-6.8) with an FP FIT result, hemorrhoids were the only abnormality. In univariate unadjusted analysis, subjects with hemorrhoids as the only abnormality did not have more positive results (9/134; 6.7%) compared with subjects without any abnormalities (43/886; 4.9%; P = .396). Logistic regression identified hemorrhoids, nonadvanced polyps, and a group of miscellaneous abnormalities, all significantly influencing false positivity. Of 1000 subjects with hemorrhoids, 67 would have FP results, of whom 18 would have FP results because of hemorrhoids only. LIMITATIONS Potential underreporting of hemorrhoids; high-risk individuals. CONCLUSIONS Hemorrhoids in individuals participating in colorectal cancer screening will probably not lead to a substantial number of false-positive test results.