title: A Pathological Study of Residual Cancer in the Esophageal Wall Following Neoadjuvant Chemoradiotherapy: Focus on Esophageal Squamous Cell Carcinoma Patients with False Negative Preoperative Endoscopic Biopsies.
abstract: BACKGROUND
  Endoscopic biopsy examinations after neoadjuvant chemoradiotherapy (nCRT) are of limited value in patients with esophageal cancer due to the high rates of false negative (FN) findings. We sought to investigate the anatomical locations of residual tumors in esophageal squamous cell carcinoma (ESCC) patients with FN endoscopic biopsies with the ultimate goal of improving their clinical management.
  
  
  METHODS
  ESCC patients with residual cancers after nCRT which were not identified by preoperative endoscopic biopsy were deemed eligible. All of the surgical specimens were re-reviewed with a special focus on (1) distribution of residual cancer in each esophageal layer; (2) tumor regression grade (TRG); and (3) shortest distance between the lumen and the residual tumor.
  
  
  RESULTS
  Among the 49 ESCC patients with FN biopsy results, a strong 'layer-dependent' tumor regression was observed. There was a preferential clearing of esophageal cancer cells located in the adventitia, followed by muscle and the submucosal (SM) and mucosal (M) layers (p < 0.001). Residual malignancies located in the muscle layer or the adventitia without simultaneous involvement of the M/SM layers were rare (n = 3; 6.1 %). TRG following nCRT did not affect the rate of M/SM involvement (p = 0.55) but was inversely associated with the distance between the lumen and residual cancer (mean distance in patients with TRG of 2, 3, and 4 was 1.1, 0.82, and 0.37 mm, respectively; p = 0.041).
  
  
  CONCLUSIONS
  Most ESCC patients who show FN endoscopic biopsies following nCRT still have detectable lesions in the M/SM layers. Aggressive biopsy protocols may potentially improve detection rates.
authors: Division of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan.|College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors: Yin-Kai
authors: YK
authors: Chao
authors: Division of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan.|College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors: Chang-Yo
authors: CY
authors: Tsai
authors: Division of Hematology/Oncology, Chang Gung Memorial Hospital, Linkou, Taiwan.|College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors: Hsien-Kun
authors: HK
authors: Chang
authors: Department of Radiation Oncology, Chang Gung Memorial Hospital, Linkou, Taiwan.|College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors: Chen-Kan
authors: CK
authors: Tseng
authors: Division of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan.|College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors: Yun-Hen
authors: YH
authors: Liu
authors: Department of Pathology, Chang Gung Memorial Hospital, Linkou, Taiwan. taki.yeh@gmail.com.|College of Medicine, Chang Gung University, Taoyuan, Taiwan. taki.yeh@gmail.com.
authors: Chi-Ju
authors: CJ
authors: Yeh
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000628:therapy*; D059186:Chemoradiotherapy, Adjuvant; D004938:Esophageal Neoplasms / Q000473:pathology* / Q000628:therapy*; D016629:Esophagectomy; D004945:Esophagoscopy; D004947:Esophagus / Q000473:pathology*; D005188:False Negative Reactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000473:pathology; D009130:Muscle, Smooth / Q000473:pathology; D020360:Neoadjuvant Therapy; D018365:Neoplasm, Residual; D011237:Predictive Value of Tests; D057234:Preoperative Period; D012189:Retrospective Studies