Heiko Pohl

Incomplete Polyp Resection During Colonoscopy—Results of the Complete Adenoma Resection (CARE) Study

BACKGROUND & AIMS Although the adenoma detection rate is used as a measure of colonoscopy quality, there are limited data on the quality of endoscopic resection of detected adenomas. We determined the rate of incompletely resected neoplastic polyps in clinical practice. METHODS We performed a prospective study on 1427 patients who underwent colonoscopy at 2 medical centers and had at least 1 nonpedunculated polyp (5-20 mm). After polyp removal was considered complete macroscopically, biopsies were obtained from the resection margin. The main outcome was the percentage of incompletely resected neoplastic polyps (incomplete resection rate [IRR]) determined by the presence of neoplastic tissue in post-polypectomy biopsies. Associations between IRR and polyp size, morphology, histology, and endoscopist were assessed by regression analysis. RESULTS Of 346 neoplastic polyps (269 patients; 84.0% men; mean age, 63.4 years) removed by 11 gastroenterologists, 10.1% were incompletely resected. IRR increased with polyp size and was significantly higher for large (10-20 mm) than small (5-9 mm) neoplastic polyps (17.3% vs 6.8%; relative risk = 2.1), and for sessile serrated adenomas/polyps than for conventional adenomas (31.0% vs 7.2%; relative risk = 3.7). The IRR for endoscopists with at least 20 polypectomies ranged from 6.5% to 22.7%; there was a 3.4-fold difference between the highest and lowest IRR after adjusting for size and sessile serrated histology. CONCLUSIONS Neoplastic polyps are often incompletely resected, and the rate of incomplete resection varies broadly among endoscopists. Incomplete resection might contribute to the development of colon cancers after colonoscopy (interval cancers). Efforts are needed to ensure complete resection, especially of larger lesions. ClinicalTrials.gov Number: NCT01224444.

The American Society for Gastrointestinal Endoscopy PIVI (Preservation and Incorporation of Valuable Endoscopic Innovations) on real-time endoscopic assessment of the histology of diminutive colorectal polyps

The PIVI (Preservation and Incorporation of Valuable endoscopic Innovations) initiative is an ASGE program whose objectives are to identify important clinical questions related to endoscopy and to establish a priori diagnostic and/or therapeutic thresholds for endoscopic technologies designed to resolve these clinical questions. Additionally, PIVIs may also outline the data and or the research study design required for proving an established threshold is met. Once endoscopic technologies meet an established PIVI threshold, those technologies are appropriate to incorporate into clinical practice presuming the appropriate training in that endoscopic technology has been achieved. The ASGE encourages and supports the appropriate use of technologies that meet its established PIVI thresholds. The PIVI initiative was developed primarily to direct endoscopic technology development toward resolving important clinical issues in endoscopy. The PIVI initiative is also designed to minimize the possibility that potentially valuable innovations are prematurely abandoned due to lack of utilization and to avoid widespread use of an endoscopic technology before clinical studies documenting their effectiveness have been performed. The following document, or PIVI, is one of a series of statements defining the diagnostic or therapeutic threshold that must be met for a technique or device to become considered appropriate for incorporation into clinical practice. It is also meant to serve as a guide for researchers or those seeking to develop technologies that are designed to improve digestive health outcomes. An ad hoc committee under the auspices of the existing ASGE Technology and Standards of Practice Committees Chairs develops PIVIs. An expert in the subject area chairs the PIVI, with additional committee members chosen for their individual expertise. In preparing this document, evidence-based methodology was employed, using a MEDLINE and PubMed literature search to identify pertinent clinical studies on the topic. PIVIs are ultimately submitted to the ASGE Governing Board for approval, as is done for all Technology and Standards of Practice documents. This document is provided solely for educational and informational purposes and to support incorporating these endoscopic technologies into clinical practice. It should not be construed as establishing a legal standard of care.

Esophageal Adenocarcinoma Incidence: Are We Reaching the Peak?

Background: A steep increase in the incidence of esophageal adenocarcinoma has been observed between 1973 and 2001, but recent trends have not been reported. Our aim was to examine recent trends in esophageal adenocarcinoma incidence. Methods: We used the Surveillance Epidemiology and End Results database of the National Cancer Institute to identify all patients who were diagnosed with esophageal adenocarcinoma between 1973 and 2006. Incidence trends were analyzed for esophageal adenocarcinoma overall and by stage using joinpoint regression. Results: Overall esophageal adenocarcinoma incidence increased from 3.6 per million in 1973 to 25.6 per million in 2006. Incidence trend analysis, however, suggests that the increase has slowed, from an 8.2% annual increase prior to 1996 to 1.3% increase in subsequent years (P = 0.03). Stage-specific trend analyses suggest that the change in overall esophageal adenocarcinoma incidence largely reflects a plateau in the incidence of early stage disease. Its slope has changed direction, from a 10% annual increase prior to 1999 to a 1.6% decline in subsequent years (P = 0.01). Conclusions: The incidence of early stage esophageal adenocarcinoma seems to have plateaued. Impact: Although definitive conclusions will require additional years of data, the plateau in early stage disease might portend stabilization in the overall incidence of esophageal adenocarcinoma. Cancer Epidemiol Biomarkers Prev; 19(6); 1468–70. ©2010 AACR.

Stepwise radical endoscopic resection for eradication of Barrett's oesophagus with early neoplasia in a cohort of 169 patients

Background and Aims Endoscopic resection is safe and effective to remove early neoplasia (ie,high-grade intra-epithelial neoplasia/early cancer) in Barretts oesophagus. To prevent metachronous lesions during follow-up, the remaining Barretts oesophagus can be removed by stepwise radical endoscopic resection (SRER). The aim was to evaluate the combined experience in four tertiary referral centres with SRER to eradicate Barretts oesophagus with early neoplasia. Methods Design: Retrospective cohort study. Setting: Four tertiary referral centres. Participants: 169 patients (151 males, age 64 years (IQR 57–71), Barretts oesophagus 3 cm (IQR 2–5)) with early neoplasia in Barretts oesophagus ≤5 cm, without deep submucosal infiltration or lymph node metastases, treated by SRER between January 2000 and September 2006. Intervention: Endoscopic resection every 4–8 weeks, until complete endoscopic and histological eradication of Barretts oesophagus and neoplasia. Results According to intention-to-treat analysis complete eradication of all neoplasia and all intestinal metaplasia by the end of the treatment phase was reached in 97.6% (165/169) and 85.2% (144/169) of patients, respectively. One patient had progression of neoplasia during treatment and died of metastasised adenocarcinoma (0.6%). After median follow-up of 32 months (IQR 19–49), complete eradication of neoplasia and intestinal metaplasia was sustained in 95.3% (161/169) and 80.5% (136/169) of patients, respectively. Acute, severe complications occurred in 1.2% of patients, and 49.7% of patients developed symptomatic stenosis. Conclusions SRER of Barretts oesophagus ≤5 cm containing early neoplasia appears to be an effective treatment modality with a low rate of recurrent lesions during follow-up. The procedure, however, is technically demanding and is associated with oesophageal stenosis in half of the patients.

Colorectal cancers detected after colonoscopy frequently result from missed lesions.

BACKGROUND & AIMS Colorectal cancers (CRCs) that are detected in patients who have received colonoscopies (interval cancers) arise from missed lesions, incomplete resections of adenomas, or de novo. We estimated rates of interval cancer from missed lesions. METHODS Adenoma miss rates, cancer prevalence among patients with adenoma (based on size), and rates of adenoma-to-cancer transitions were estimated from the literature. We used a model to apply these risk estimates to a hypothetical average-risk population that received screening colonoscopies. We calculated the proportion of individuals with tumors missed at the baseline colonoscopy and tumors that arose from missed adenomas during a 5-year follow-up period. Sensitivity analyses were performed to assess robustness. RESULTS We found that 0.7 per 1000 persons undergoing a screening colonoscopy had a cancer that was missed at the baseline colonoscopy and an additional 1.1 per 1000 subsequently developed cancer from a missed adenoma. Therefore, the expected rate of individuals with CRC, based on missed adenomas, was 1.8 per 1000 persons within 5 years. By using the most conservative assumptions-a low miss rate and low prevalence of cancer in adenomas-0.5 per 1000 persons would have a detectable CRC within 5 years after a screening colonoscopy. In contrast, using the highest reported miss rates and cancer prevalence, CRCs from missed lesions would occur in 3.5 per 1000 screened persons. CONCLUSIONS A significant number of patients undergoing a screening colonoscopy that did not detect cancer actually have a malignant lesion or adenoma that could progress in a short interval. Most interval cancers might reflect missed rather than new lesions. Improving adenoma detection could reduce the rate of interval cancers.

Probe-based confocal laser endomicroscopy compared with standard four-quadrant biopsy for evaluation of neoplasia in Barrett’s esophagus

BACKGROUND AND STUDY AIMS Surveillance of Barretts esophagus includes endoscopic inspection with biopsy of suspicious lesions followed by four-quadrant biopsy of the remaining mucosa. We assessed the ability of probe-based confocal laser endomicroscopy (pCLE) to replace biopsy in the endoscopic evaluation of patients with Barretts esophagus in a prospective and controlled setting. PATIENTS AND METHODS A total of 68 patients who were referred for endoscopic assessment of Barretts esophagus were included across three centers. pCLE recordings were interpreted live during the examination as well as in a blinded manner at least 3 months after endoscopy. pCLE diagnosis of neoplasia based on pre-defined criteria was compared with histopathology from suspicious as well as four-quadrant biopsies. RESULTS A total of 670 pairs of biopsies and pCLE video sequences were available for analysis, with neoplasia (high-grade dysplasia or cancer) being histologically diagnosed in 8.3 %. Specificity and negative predictive value of pCLE in excluding neoplasia was 0.97 (90 %CI 0.95 - 0.98) and 0.93 (0.91 - 0.95) for the blinded evaluation, and 0.95 (0.90 - 0.98) and 0.92 (0.90 - 0.94) for the on-site assessment. Positive predictive values (PPVs) and sensitivity were rather poor for both settings (46 %/28 % [blinded] and 18 %/12 % [on-site], respectively). CONCLUSIONS pCLE can be regarded as non-inferior to endoscopic biopsy in excluding neoplasia of Barretts esophagus mucosa. However, due to its low PPV and sensitivity, pCLE may currently not replace standard biopsy techniques for the diagnosis of Barretts esophagus and associated neoplasia. Further technical development of pCLE and a better understanding of its role in relation to other imaging technologies are necessary.

Risk Factors in the Development of Esophageal Adenocarcinoma

OBJECTIVES:It is assumed that esophageal adenocarcinoma is the end result of a stepwise disease process that transitions through gastroesophageal reflux disease (GERD) and Barretts esophagus. The aim of this study was to examine at what stage known risk factors exert their influence toward the progression to cancer.METHODS:We enrolled 113 consecutive outpatients without GERD, 188 with GERD, 162 with Barretts esophagus, and 100 with esophageal adenocarcinoma or high-grade dysplasia (HGD). All patients underwent a standard upper endoscopy and completed a standardized questionnaire about their social history, symptoms, dietary habits, and prescribed medications. We used adjusted logistic regression analysis to assess risk factors between each two consecutive disease stages from the absence of reflux disease to esophageal adenocarcinoma.RESULTS:Overall, male gender, smoking, increased body mass index (BMI), low fruit and vegetable intake, duration of reflux symptoms, and presence of a hiatal hernia were risk factors for cancer/HGD. However, different combinations of risk factors were associated with different disease stages. Hiatal hernia was the only risk factor to be strongly associated with the development of GERD. For GERD patients, male gender, age, an increased BMI, duration of reflux symptoms, and presence of a hiatal hernia were all associated with the development of Barretts esophagus. Finally, the development of cancer/HGD among patients with Barretts esophagus was associated with male gender, smoking, decreased fruit and vegetable intake, and a long segment of Barretts esophagus, but not with age, BMI, or a hiatal hernia.CONCLUSIONS:While some risk factors act predominantly on the initial development of reflux disease, others appear to be primarily responsible for the development of more advanced disease stages.

Endoscopic versus surgical therapy for early cancer in Barrett's esophagus: a decision analysis

BACKGROUND Esophagectomy for early esophageal adenocarcinoma is associated with increased operative mortality and morbidity, but possibly a decreased recurrence rate compared with endoscopic therapy when using EMR and radiofrequency ablation. OBJECTIVE To compare the cost-effectiveness of esophagectomy and endoscopic therapy in the treatment of early esophageal adenocarcinoma. DESIGN Decision analysis model. MAIN OUTCOME MEASUREMENTS Incremental cost-effectiveness ratio. RESULTS During the 5-year study period, endoscopic therapy cost

Length of Barrett's oesophagus and cancer risk: implications from a large sample of patients with early oesophageal adenocarcinoma

17,000.00 and yielded 4.88 quality-adjusted life years, compared with

Long-term recurrence of neoplasia and Barrett's epithelium after complete endoscopic resection

28,000.00 and 4.59, respectively, for esophagectomy. Varying the recurrence rates of cancer or Barretts esophagus metaplasia after endoscopic therapy did not change the overall outcome. The sensitivity analysis demonstrated, however, that the outcome depended on the rate of lymph node involvement and operative mortality. Under the best of circumstances in favor of esophagectomy, such as 2% operative mortality, no reduced quality of life after esophagectomy, and a low 5-year survival rate after recurrence of endoscopic ablation, the risk of positive lymph nodes still needed to exceed 25% before esophagectomy became the preferred treatment option. This threshold is twice as high as the values reported for early submucosal cancer invasion. LIMITATIONS Limited data are available about the long-term outcome of EMR and radiofrequency ablation. CONCLUSIONS Endoscopic therapy for early Barretts esophagus adenocarcinoma is more effective and less expensive than esophagectomy. Even in early esophageal adenocarcinoma with submucosal invasion, endoscopic therapy is a cost-effective alternative to esophagectomy, especially in patients with a high operative risk.