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Objectives: The objective of this study was to review the prognostic factors for increased survival after salvage esophagectomy after definitive chemoradiotherapy for esophageal squamous carcinoma and determine the importance of lymphadenectomy from a prognostic view. Methods: Clinical data for all patients from January 1999 to December 2012 who underwent salvage esophagectomy for residual tumor or tumor recurrence after definitive chemoradiotherapy were retrospectively collected. Survival was determined and prognostic factors were analyzed with univariate and multivariate analyses. Results: Survival after 1, 3, and 5 years postoperatively was 74.4%, 39.8%, and 29.5%, respectively. The independent predictive factors for increased postoperative survival were tumor recurrence rather than residual tumor as the indication for salvage surgery (P < .001; odds ratio [OR], 0.292); complete tumor resection (P < .001; OR, 4.520); N category (P = .089; OR, 1.304); M category (P = .081; OR, 2.215), and total mediastinal dissection with 15 or more dissected mediastinal lymph nodes (P = .034; OR, 0.546). Conclusions: Salvage indications of recurrence, earlier disease, and complete tumor resection are related to longer survival. The total area of mediastinal dissection with a sufficient number of dissected mediastinal lymph nodes improves survival. Additional neck dissection does not add benefit. The optimal procedure for lymph node dissection in salvage esophagectomy should be established in future studies. [Copyright &y& Elsevier]

Background: This study investigated the incidence, diagnosis, treatment, and risk factors for nonmalignant airway erosion after subtotal esophagectomy for thoracic esophageal carcinoma. Methods: Clinical data from all patients with thoracic esophageal carcinoma who underwent right transthoracic subtotal esophagectomy from 2000 to 2012 at our institution were retrospectively reviewed, and the clinical course and outcome of those who developed airway erosion were investigated in detail. Risk factors for airway erosion were calculated by multivariate analysis. Results: Of 1,091 patients enrolled, 15 patients (1.4%) developed nonmalignant airway erosion, which occurred at postoperative day (POD) 7 to 92 (median, 24). Anastomotic leakage or gastric-tube necrosis was detected prior to airway erosion in 14 cases (93.3%). Endoscopic and surgical therapy was administrated to 3 patients. Airway erosion was cured in 9 patients (60.0%). Five patients died from airway erosion directly (mortality, 33.3%). Alimentary leakage or necrosis (p < 0.001), preoperative radiotherapy (p = 0.004), and reconstruction through the posterior mediastinal route (p = 0.051) were independent risk factors for airway erosion development. Conclusions: Airway erosion is a fatal complication after subtotal esophagectomy. Preoperative radiotherapy dramatically increases the risk of developing airway erosion and reduces the probability of spontaneous healing. Aggressive treatment of alimentary leakage or necrosis and reconstruction through the anterior route help to decrease the risk of airway erosion, especially in high-risk patients. [Copyright &y& Elsevier]

Background: We summarize the experience of diagnosis and surgical therapy for primary malignant melanoma of the esophagus (PMME). Methods: Clinical data of 13 patients diagnosed as having PMME treated by surgery as their primary therapy from 2000 to 2012 were retrospectively analyzed, and survival information was collected through follow-up. Results: The average age (± standard deviation) of participants in this study was 66.4 ± 7.6 years, and 84.6% were male. Overall, 61.5% of tumors were located in the lower thoracic esophagus. The accuracies of clinical T stage, N stage, and TNM stage were 53.9%, 46.2%, and 38.5%, respectively, compared with pathological staging (kappa = 0.252, p = 0.023). Surgical mortality and morbidity were 7.7% and 53.9%, respectively. The incidence of lymph node metastasis for patients with tumor invading within the mucosa was 0, but increased to 42.9% (3 of 7) with tumor invading to the submucosal layer. Primary malignant melanoma of the esophagus in the mid third of the thoracic esophagus had a greater chance to metastasize to perigastric lymph nodes (2 of 5) than to middle mediastinal lymph nodes (1 of 5). For PMME located at the lower third of the thoracic esophagus, upper mediastinal lymph node metastasis was more likely to occur (2 of 4) with tumor invasion penetrating the proper muscle layer. Recurrence occurred within 1 year in all patients with tumor later than Stage Ib. The most common recurrent organ was the liver. The overall 1-year and 5-year postoperative survival rates were 54.0% and 35.9%, respectively, and lymph node metastasis was the independent predictive factor for postoperative survival (p = 0.013; odds ratio, 15.05). Conclusions: Despite the similarity in lymph node metastatic patterns to squamous cell carcinoma, PMME is more inclined to distant metastasis. Clinical staging was inconsistent with pathological staging for PMME based on endoscopy and computed tomography. Surgical therapy was the optimal treatment for PMME at an earlier stage. Early diagnosis and aggressive lymph node dissection were beneficial for accurate staging, potentially reducing recurrence and thus improving survival. [Copyright &y& Elsevier]

Somatic base substitution mutations of frequencies at the 10-6/bp level are expected to be present in many biomedical samples, such as tissues exposed to carcinogenic factors and exhausted stem cells. However, measurement of such rare mutations has been very difficult in human DNA samples. Here, we invented the use of 100 copies of genomic DNA as a template for amplicon deep sequencing so that a real mutation in a single DNA molecule would be detected at a variant allele frequency of 1% while sequencing errors have less frequency. In addition, we selected 15,552 error-resistant base positions whose mutation frequency was expected to reflect that of base positions that can drive carcinogenesis or potentially even of the entire genome. The validity of the method was first confirmed by the successful detection of mutations premixed at the frequency of 0.1%. Second, increasing mutation frequencies (4-60 × 10-6/bp) were successfully detected in cells treated with increasing doses of one of two mutagens, and their signature mutations were detected. The ratio of non-synonymous mutations to synonymous mutations time-dependently decreased after treatment with a mutagen, supporting the neutral theory of molecular evolution for somatic mutations. Importantly, gastric mucosae exposed to Helicobacter pylori infection was shown to have significantly higher mutation frequency than those without. These results demonstrated that our new method can be used to measure rare base substitution mutations at the 10-6/bp level, and is now ready for a wide range of applications. [ABSTRACT FROM AUTHOR]