Masashi Tamaoki

Background: Talaporfin sodium photodynamic therapy (Talaporfin-PDT) shows a high local complete response (L-CR) rate for local failure after chemoradiotherapy in esophageal cancer; however, some patients do not achieve L-CR. We investigated the treatment resistance factors associated with Talaporfin-PDT for local control. Methods: This study included 55 consecutive patients with ycT1-2 esophageal cancer who received Talaporfin-PDT. We investigated the L-CR rate, cumulative survival rate according to local effect, and treatment resistance factors associated with Talaporfin-PDT for local control using a multivariate logistic regression model. Results: The L-CR rate was 65.5% (95% confidence interval [CI]: 52.3–76.6). During the median follow-up of 17.8 months (range, 1.7–69.3), the 1-year overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS) rates were significantly higher in patients who achieved L-CR than in those who did not: 97.0% vs. 75.6% ( P = 0.008), 64.6% vs. 0% ( P < 0.001), and 97.0% vs. 85.7% ( P = 0.005), respectively. In the multivariate logistic regression model, esophageal stenosis before Talaporfin-PDT was an independent predictor of local failure after Talaporfin-PDT (odds ratio: 5.626, 95% CI: 1.051–30.124, P = 0.044). The 1-year OS and DSS rates were significantly lower in patients with stenosis before Talaporfin-PDT than in those without: 75.0% vs. 92.4% ( P = 0.015) and 85.7% vs. 94.6% ( P = 0.015), respectively. Conclusions: Esophageal stenosis before Talaporfin-PDT was associated with resistance to local control and poor survival. The indications for the use of Talaporfin-PDT in patients with stenosis should be considered carefully.

INTRODUCTION: The early detection of gastric neoplasms (GNs) leads to favorable treatment outcomes. The latest endoscopic system, EVIS X1, includes third-generation narrow-band imaging (3G-NBI), texture and color enhancement imaging (TXI), and high-definition white-light imaging (WLI). Therefore, this randomized phase II trial aimed to identify the most promising imaging modality for GN detection using 3G-NBI and TXI. METHODS: Patients with scheduled surveillance endoscopy after a history of esophageal cancer or GN or preoperative endoscopy for known esophageal cancer or GN were randomly assigned to the 3G-NBI, TXI, or WLI groups. Endoscopic observations were performed to detect new GN lesions, and all suspected lesions were biopsied. The primary endpoint was the GN detection rate during primary observation. Secondary endpoints were the rate of missed GNs, early gastric cancer detection rate, and positive predictive value for a GN diagnosis. The decision rule had a higher GN detection rate between 3G-NBI and TXI, outperforming WLI by >1.0%. RESULTS: Finally, 901 patients were enrolled and assigned to the 3G-NBI, TXI, and WLI groups (300, 300, and 301 patients, respectively). GN detection rates in the 3G-NBI, TXI, and WLI groups were 7.3, 5.0, and 5.6%, respectively. The rates of missed GNs were 1.0, 0.7, and 1.0%, the detection rates of early gastric cancer were 5.7, 4.0, and 5.6%, and the positive predictive values for the diagnosis of GN were 36.5, 21.3, and 36.8% in the 3G-NBI, TXI, and WLI groups, respectively. DISCUSSION: Compared with TXI and WLI, 3G-NBI is a more promising modality for GN detection.

Multiple development of esophageal squamous-cell carcinoma is explained by field cancerization and is associated with alcohol consumption and smoking. We investigated the association between the development of second primary esophageal squamous-cell carcinoma after endoscopic resection for esophageal squamous-cell carcinoma and genetic polymorphisms related to alcohol and nicotine metabolism. The study group comprised 56 patients with esophageal squamous-cell carcinoma after endoscopic resection. The main variables were the following: (i) cumulative incidence and total number of second primary esophageal squamous-cell carcinoma according to genetic polymorphisms in alcohol dehydrogenase 1B, aldehyde dehydrogenase 2 and cytochrome P450 2A6; and (ii) risk factors of second primary esophageal squamous-cell carcinoma identified using a multivariate Cox proportional-hazards model. The frequencies of alcohol dehydrogenase 1B, aldehyde dehydrogenase 2 and cytochrome P450 2A6 genetic polymorphisms in the buccal mucosa were analyzed. The median follow-up was 92.8 months (range: 2.7–134.2). Slow-metabolizing alcohol dehydrogenase 1B was associated with a higher 7-year cumulative incidence of second primary esophageal squamous-cell carcinoma (fast-metabolizing alcohol dehydrogenase 1B vs slow-metabolizing alcohol dehydrogenase 1B: 20.5% vs 71.4%, P = 0.006). Slow-metabolizing alcohol dehydrogenase 1B (relative risk [95% confidence interval]: 3.17 [1.49–6.73]), inactive aldehyde dehydrogenase 2 (2.17 [1.01–4.63]) and poorly-metabolizing cytochrome P450 2A6 (4.63 [1.74–12.33]) had a significantly higher total number of second primary esophageal squamous-cell carcinoma per 100 person-years. In the multivariate Cox proportional-hazards model, slow-metabolizing alcohol dehydrogenase 1B was a significant risk factor of the development of second primary esophageal squamous-cell carcinoma (hazard ratio 9.92, 95% confidence interval: 2.35–41.98, P = 0.0018). Slow-metabolizing alcohol dehydrogenase 1B may be a significant risk factor for the development of second primary esophageal squamous-cell carcinoma. In addition, inactive aldehyde dehydrogenase 2 and poorly-metabolizing cytochrome P450 2A6 may be important factors.