Shedding light on esophageal neoplasia: refining its detection and management

Abstract

This thesis aimed to optimize early diagnosis and management of esophageal neoplasia, focusing on both histological subtypes: esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). It is divided into two parts: (I) improving surveillance and detection of early EAC in patients with Barrett’s esophagus (BE), and (II) optimizing characterization and management of ESCC. Part I: Optimizing Detection of Early Neoplasia in Barrett’s Esophagus BE is a premalignant condition for which endoscopic surveillance is recommended to detect neoplasia at an early, treatable stage. Several studies were conducted to improve the quality of these surveillance endoscopies in community practice. Detecting neoplasia in the upper gastrointestinal tract can be challenging, as neoplastic lesions can be subtle. In order to improve mucosal visibility during upper endoscopy, we evaluated the optimal timing of administering premedication prior to upper endoscopy in chapter 2. In a randomized trial of 386 patients, early or split-dose administration yielded significantly better visibility compared to late administration. We therefore recommend to optimize mucosal visibility by early simethiconem administration, either as a single administration or in a split-dose regimen. In chapter 3, we compared different biopsy methods and techniques during BE surveillance endoscopies. A randomized trial (107 patients, 1,024 biopsies) showed that the single-biopsy method produced larger tissue samples than the double-biopsy method, especially when combined with the turn-and-suction technique. Implementation of this approach in community practice increased biopsy size by 18%, supporting its routine use. Chapter 4 presented a systematic review and meta-analysis including eight studies, showing that adherence to the recommended four-quadrant random biopsy protocol is associated with increased dysplasia detection (RR 1.59; 95% CI 1.17–2.16). Therefore, in chapter 5, we evaluated whether the clustering of BE surveillance endoscopies on dedicated endoscopy lists performed by dedicated endoscopists would increase adherence to BE surveillance guidelines in community practice. Among 1,244 patients across 18 hospitals, adherence to biopsy and interval guidelines was significantly higher on dedicated lists (85% vs. 66% and 60% vs. 47%, respectively). Chapter 6 evaluated acetic acid chromoendoscopy in a stepped-wedge cluster randomized trial of 2,267 patients. This technique did not improve overall or targeted detection of dysplasia or EAC. Thus, acetic acid chromoendoscopy-guided targeted biopsies cannot replace the standard random biopsy protocol. Part II: Optimizing Management of Esophageal Squamous Cell Neoplasia Due to the low incidence of ESCC in Western populations, evidence for treatment outcomes is limited. Chapter 7 analyzed 68 ESCC patients treated with endoscopic submucosal dissection (ESD) in four Dutch centers. Technical success rate was high (97%), but curative resection was achieved in only 52%. Five-year overall and cancer-specific survival were 62% and 86%, respectively. As many deaths were unrelated to ESCC, additional therapy after noncurative resection should be individualized. In chapter 8, we assessed the diagnostic accuracy of the Japan Esophageal Society (JES) microvessel classification for estimating ESCC invasion depth. Among 113 ESCC lesions assessed by nine endoscopists, overall accuracy was 44–53%, limiting its clinical value. However, the absence of type B3 vessels reliably predicted superficial, endoscopically resectable ESCC (negative predictive value 80–85%).