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Background Endoscopic submucosal dissection (ESD) is gradually turning into the standard treatment for superficial esophageal squamous cell carcinoma (SESCC), however, the long-term outcomes have hardly ever been reported outside Japan. Method We consecutively recruited patients with SESCC who had received ESD treatment at E-Da Hospital. The demographics, pathological characteristics, and Lugol staining background pattern (type A or B: none or 10 small or multiform LVLs) were collected, and then correlated to outcomes and survival. Results Total of 229 lesions were enrolled and the mean lesion size was 3.28 ± 1.69 (range 1–10) cm. 72% of the lesions had a type C-D Lugol staining background pattern. After ESD, the en bloc and R0 resection rates were 93.9% and 83.5%, respectively. Forty-nine subjects developed complications, including six (2.6%) with major bleeding, two (0.9%) with perforation, and 41 (17.9%) with strictures. Pathological staging showed that 19 cases had deep submucosal cancer invasion and subsequently received adjuvant therapies. During a mean follow-up period of 52.6 (range 3–146) months, 41 patients developed metachronous recurrence. The patients with a type C-D Lugol staining background pattern were associated with a higher risk of recurrence than those with few LVLs (log-rank P = 0.019). The 10-year survival rate was more than 90%, and only eight patients died of ESCC. Conclusion ESD has excellent long-term outcomes but a high risk of metachronous recurrence. The Lugol staining pattern over the background mucosa could offer the risk stratification of metachronous recurrence.

Somatic mutations including the background mucosa in patients with Lugol‐voiding lesions (LVLs) are still not well known. The aim of this study was to evaluate the somatic mutations of the background mucosa in patients with LVLs (Squamous cell carcinoma (SCC), intraepithelial neoplasia (IN), and hyperplasia). Twenty‐five patients with LVLs (9 with SCC, 6 with IN, and 10 with hyperplasia) were included. A targeted sequence was performed for LVLs and background mucosa using an esophageal cancer panel. Each mutation was checked whether it was oncogenic or not concerning OncoKB. In LVLs, TP53 was the most dominant mutation (80%). Furthermore, 72% of TP53 mutations was putative drivers. In background mucosa, NOTCH1 was the most dominant mutation (88%) and TP53 was the second most dominant mutation (48%). Furthermore, 73% of TP53 mutations and 8% of NOTCH1 mutations were putative drivers. Putative driver mutations of TP53 had significantly higher allele frequency (AF) in SCC than in IN and hyperplasia. Conversely, putative driver mutations of NOTCH1 did not have a significant accumulation of AF in the progression of carcinogenesis. Furthermore, in SCC, AF of TP53 mutations was significantly higher in LVLs than in background mucosa, but not in IN and hyperplasia. Regarding NOTCH1, a significant difference was not observed between LVLs and background mucosa in each group. The background mucosa in patients with LVLs already had putative driver mutations such as TP53 and NOTCH1. Of these two genes, TP53 mutation could be the main target gene of carcinogenesis in esophageal SCC. Clinical Trials registry: UMIN000034247., The background mucosa in patients with LVLs already has accumulated gene mutations. Notably, many putative driver mutations were confirmed in TP53 and NOTCH1. The TP53 could be the main target gene of the carcinogenesis in esophageal SCC; this mutation was also found in the background mucosa in high‐risk patients.

Background The detection rate of narrow-band imaging (NBI) for superficial esophageal squamous cell carcinoma (SESCC), including high-grade intraepithelial neoplasia, is significantly higher than that of white-light endoscopy. However, there are SESCCs that are undetectable by NBI but detectable by Lugol chromoendoscopy (LCE) and the characteristics of these SESCCs are still unknown. Thus, this study aimed to clarify the characteristics of SESCC that are undetectable using NBI. Methods Patients with current SCC or a history of SCC in the head and neck or in the esophagus were enrolled. The inspection of the esophagus was initiated by NBI, followed by LCE. Biopsies were taken of all suspected SESCC lesions during NBI observation and Lugol-voiding lesions (LVLs) that were irregularly shaped and >5 mm and/or pink in color during LCE observation. The characteristics of SESCC that were undetectable with NBI were statistically analysed. Results Overall, 147 lesions in 105 cases were histologically diagnosed as SESCC. Twenty in 15 cases were NBI-undetectable lesions, all of which were macroscopic flat type (0-IIb). The median sizes of the NBI-undetectable lesions and NBI-detectable lesions were both 15 mm (P = 0.47). Multivariate analysis revealed independent factors for NBI-undetectable lesions such as numerous irregularly shaped LVLs (odds ratio [OR]: 4.94, 95% confidence interval [CI]: 1.39–17.5, P Conclusions The detection of SESCCs with NBI is challenging when lesions are morphologically completely flat, in cases with numerous irregularly shaped LVLs, and if located at the anterior wall.

Background: We conducted a systematic review and meta-analysis of existing data from observational studies to assess the strength of the association of alcohol drinking with second primary cancer risk in patients with upper aerodigestive tract (UADT; oral cavity, pharynx, larynx, and esophagus) cancer. Methods: PubMed and Embase were searched up to July 2012 and the reference lists of studies included in the analysis were examined. Random-effects models were used to estimate summary relative risks (RR) and 95% confidence interval (CI). Results: Nineteen studies, 8 cohort and 11 case–control studies, were included. In highest versus lowest meta-analyses, alcohol drinking was associated with significantly increased risk of UADT second primary cancers (RR, 2.97; 95% CI, 1.96–4.50). Significantly increased risks were also observed for UADT and lung combined (RR, 1.90; 95% CI, 1.16–3.11) and all sites (RR, 1.60; 95% CI, 1.22–2.10) second primary cancers. For an increase in the alcohol intake of 10 grams per day, dose–response meta-analysis resulted in a significantly increased RR of 1.09 (95% CI, 1.04–1.14) for UADT second primary cancers. Conclusions: Alcohol drinking in patients with UADT cancer is associated with an increased risk of second primary cancers. Studies conducted in alcohol drinking patients with UADT cancer and evaluating the effect of alcohol cessation on second primary cancer and other outcomes are needed. Impact: Our results emphasize the importance of prevention policies aiming to reduce alcohol drinking. Health-care professionals should encourage alcohol drinking patients with UADT cancer to reduce their consumption and reinforce the surveillance of this at-risk subpopulation. Cancer Epidemiol Biomarkers Prev; 23(2); 324–31. ©2013 AACR.