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• We assessed risk factors for death unrelated to cancer after definitive RT for HNC. • History of surgery for EC and simultaneous RT for EC are significant risk factors. • Simultaneous RT for HNC and EC should be used with caution. The incidence of hypopharyngeal and supraglottic cancer (HSC) is high in Japan. This study aimed to retrospectively identify risk factors for death unrelated to cancer and death from aspiration pneumonia after definitive radiotherapy (RT) for HSC. Overall, 391 patients who began definitive RT for HSC between 2006 and 2014 were identified from the Osaka International Cancer Institute electronic database. Among 391 patients, 33 had a history of surgery for esophageal cancer (EC) and 19 received simultaneous RT for synchronous EC. The cause of death was divided into 3 main categories: "cancer under study," "other malignancy," and "unrelated to cancer." Cox proportional hazard model was used to estimate the hazard ratio (HR). The median follow-up for survivors was 8 (range 3.6–14.1) years. At the last follow-up, 202 patients died. Death from "cancer under study," "other malignancy," and "unrelated to cancer" occurred in 92 (45.5%), 55 (27.2%), and 55 (27.2%) patients, respectively. Twelve patients died from aspiration pneumonia. In multivariate analysis for death unrelated to cancer and death from aspiration pneumonia, history of surgery for EC (HR: 3.87, p < 0.001; HR: 6.84, p = 0.007, respectively) and simultaneous RT for synchronous EC (HR: 3.74, p = 0.006 ; HR: 16.37, p < 0.001, respectively) were significant risk factors. The laryngeal preservation approach by RT for HSC patients with a history of surgery for EC and simultaneous RT for synchronous EC should be used with caution. [ABSTRACT FROM AUTHOR]

Background and Aims Although endoscopic submucosal dissection (ESD) has been applied for superficial pharyngeal cancer, no prospective trials have been reported. To investigate the efficacy and safety of ESD for superficial pharyngeal cancer, we conducted a prospective phase II trial. Methods Fifty-four patients with 73 lesions were enrolled from September 2010 to August 2014, and ESD was performed. The primary endpoint was the complete resection rate. Secondary endpoints were safety, recurrence-free survival, overall survival, and incidence of metachronous pharyngeal cancer. Results Fifty-four patients had stage 0-III cancer: stage 0, n = 22; stage I, n = 14; stage II, n = 17; and stage III, n = 1. The en bloc resection rate was 100%, and the complete resection rate was 79.5% (58/73 lesions; 95% confidence interval, 68%-88%). No serious adverse events related to ESD were encountered. Four patients required nasogastric intubation and feeding. No patients required percutaneous endoscopic gastrostomy and tracheotomy. Swallowing, speech, and airway functions were preserved in all patients. One of the 54 patients died of an unrelated illness. Median follow-up was 27 months (range 6-55 months). Local cervical lymph node metastasis was observed in 1 patient, and the case was salvaged successfully with lymph node dissection. The 3-year overall and recurrence-free survival rates were 97.7% and 98.1%, respectively. Cumulative development of multiple cancers of the pharynx at 3 years was 18.4%. Conclusions ESD appears to be a safe and effective minimally invasive treatment in patients with superficial pharyngeal cancer. (Clinical trial registration number: UMIN000003623.) [ABSTRACT FROM AUTHOR]

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Highlights: [•] Radiation-induced microsatellite instability (MSI) was investigated in medaka fish. [•] msh2 −/− fish had a high frequency of spontaneous MSI. [•] p53 −/− fish had a high frequency of radiation-induced MSI. [•] p53 and msh2 suppress MSI by different pathways: mismatch removal and apoptosis. [ABSTRACT FROM AUTHOR]

Background: During the last two decades, DNA sequencing has led to the identification of numerous genes in key species; however, in most cases, their functions are still unknown. In this situation, reverse genetics is the most suitable method to assign function to a gene. TILLING (Targeting Induced Local Lesions IN Genomes) is a reversegenetic strategy that combines random chemical mutagenesis with high-throughput discovery of the induced mutations in target genes. The method has been applied to a variety of plant and animal species. Screening of the induced mutations is the most important step in TILLING. Currently, direct sequencing or nuclease-mediated screening of heteroduplexes is widely used for detection of mutations in TILLING. Both methods are useful, but the costs are substantial and turnaround times are relatively long. Thus, there is a need for an alternative method that is of higher throughput and more cost effective. Results: In this study, we developed a high resolution melting (HRM) assay and evaluated its effectiveness for screening ENU-induced mutations in a medaka TILLING library. We had previously screened mutations in the p53 gene by direct sequencing. Therefore, we first tested the efficiency of the HRM assay by screening mutations in p53, which indicated that the HRM assay is as useful as direct sequencing. Next, we screened mutations in the atr and atm genes with the HRM assay. Nonsense mutations were identified in each gene, and the phenotypes of these nonsense mutants confirmed their loss-of-function nature. Conclusions: These results demonstrate that the HRM assay is useful for screening mutations in TILLING. Furthermore, the phenotype of the obtained mutants indicates that medaka is an excellent animal model for investigating genome stability and gene function, especially when combined with TILLING. [ABSTRACT FROM AUTHOR]

Background and Aim Methods Results Conclusions Effective treatment of lesions that develop in the irradiated area of head and neck squamous cell carcinoma is a major concern. This study aimed to clarify the efficacy and safety of endoscopic resection for such lesions.Among consecutive patients who underwent endoscopic resection for histologically proven head and neck squamous cell carcinoma between January 2014 and December 2021, those who received definitive radiotherapy/chemoradiotherapy before endoscopic resection were included in this single‐center, retrospective study. Short‐ and long‐term outcomes were evaluated.Among 422 patients who underwent endoscopic resection for 615 lesions, 43 patients with 57 lesions were eligible. All 57 lesions were treated with endoscopic submucosal dissection and en bloc resection was achieved in all lesions. Grade 3 of Common Toxicity Criteria for Adverse Events v5.0 occurred in eight (19%) patients (dysphagia, seven; stricture, three; aspiration pneumonia, two; and pharyngeal necrosis, one [some cases overlapped]), but no grade ≥ 4 events occurred. Enteral nutrition by gastrostomy was temporarily required in two patients owing to dysphagia and laryngeal necrosis. During the median follow‐up of 40 (interquartile range, 29.5–61) months after endoscopic submucosal dissection for the lesions developed in the irradiated area, local recurrence and metachronous lesions developed in two (5%) and nine (21%) patients, respectively. However, total laryngectomies and tracheostomies were avoided in all patients. The 3‐year overall and disease‐specific survivals were 81% (95% confidence interval, 64%–91%) and 94% (95% confidence interval, 79%–99%), respectively.Favorable local control and safety of endoscopic submucosal dissection were demonstrated. [ABSTRACT FROM AUTHOR]

To predict occult nodal metastasis in clinical N0 patients with tongue cancer, we developed combined index (CI) : SUVmax of the largest lymph node in PET / CT by weighting coefficient plus its maximum minor axis (< 10 mm) in contrast-enhanced CT (CECT). In this retrospective study, 57 clinical N0 patients with tongue cancer, who underwent elective supraomohyoid neck dissection at cervical levels of I-III were enrolled. The cutoff value of SUVmax of 2.0 obtained using receiver operating characteristic (ROC) analysis predicted the postoperative positive cervical levels containing metastatic lymph nodes from clinical N0 cervical levels in tongue cancer patients with a sensitivity of 54.5% and a specificity of 78.2%. The cutoff value of CI with weighting coefficient of 1.5 obtained using ROC analysis was 9.8 at the maximum area under the curve of 0.750. The cutoff value of 9.8 predicted the postoperative positive cervical levels containing metastatic lymph nodes from clinical N0 cervical levels in tongue cancer patients with a sensitivity of 68.2% and a specificity of 81.5%. These findings suggest that CI of functional PET / CT and morphological CECT components might improve the diagnostic performance of occult nodal metastasis to select clinical N0 patients with tongue cancer preferable for elective neck dissection. J. Med. Invest. 68 : 154-158, February, 2021.