LINE-1 hypomethylation in gastric cancer, detected by bisulfite pyrosequencing, is associated with poor prognosis

BACKGROUND: Genome-wide DNA hypomethylation plays an important role in genomic instability and carcinogenesis. DNA methylation in the long interspersed nucleotide element-1, L1 (LINE-1) repetitive element is a good indicator of the global DNA methylation level. In some types of human neoplasms, LINE-1 methylation level is attracting interest as a predictive marker for patient prognosis. However, the prognostic significance of LINE-1 hypomethylation in gastric cancer remains unclear. METHODS: Using 203 resected gastric cancer specimens, we quantified LINE-1 methylation using bisulfite-pyrosequencing technology. A Cox proportional hazards model was used to calculate the hazard ratio (HR), adjusted for the clinical and pathological variables. RESULTS: Gastric cancers showed significantly lower LINE-1 methylation levels compared to matched normal gastric mucosa (p < 0.0001; n = 74). Tumoral LINE-1 methylation range was 11.6–97.5 on a 0–100 scale (n = 203; mean 71.4, median 74.4, standard deviation 12.9). LINE-1 hypomethylation was significantly associated with shorter overall survival [log-rank p = 0.029; univariate HR 2.01, 95 % confidence interval (CI) 1.09–3.99, p = 0.023; stage-matched HR 1.88, 95 % CI 1.02–3.74, p = 0.041; multivariate HR 1.98, 95 % CI 1.04–4.04, p = 0.036]. No significant effect modification was observed by any of the covariates in survival analysis (all p interaction >0.25). CONCLUSIONS: LINE-1 hypomethylation in gastric cancer is associated with shorter survival, suggesting that it has potential for use as a prognostic biomarker

Successful esophageal bypass surgery in a patient with a large tracheoesophageal fistula following endotracheal stenting and chemoradiotherapy for advanced esophageal cancer: case report

A 63-year-old man with esophageal achalasia for more than 20 years complained of respiratory distress. He was admitted as an emergency to the referral hospital three months previously. Computed tomography revealed tracheobronchial stenosis due to advanced esophageal cancer with tracheal invasion. He underwent tracheobronchial stenting and chemoradiotherapy. A large tracheoesophageal fistula (TEF) developed after irradiation (18 Gy) and chemotherapy, and he was unable to eat. Thereafter, he was referred to our hospital, where we performed esophageal bypass surgery using a gastric conduit. A percutaneous cardiopulmonary support system was prepared due to the risk of airway obstruction during anesthesia. A small-diameter tracheal tube inserted into the stent achieved ordinary respiratory management. No anesthesia-related problems were encountered. Oral intake commenced on postoperative day 9. He was discharged on postoperative day 23 and was able to take in sustenance orally right up to the last moment of his life. Esophageal bypass under general anesthesia can be performed in patients with large TEF with sufficient preparation for anesthetic management

Predictor for Histological Microvascular Invasion of Hepatocellular Carcinoma: A Lesson from 229 Consecutive Cases of Curative Liver Resection.

BACKGROUND: Microscopic vascular invasion is an important risk factor for recurrent hepatocellular carcinoma (HCC), even after curative liver resection or orthotopic liver transplantation. To predict microscopic portal venous invasion, the following two questions were examined retrospectively: Is it possible to detect microvascular invasion preoperatively? What are the characteristics of a group of early HCC recurrences even with no microvascular invasion? METHODS: Study 1 included 229 patients with HCC who underwent curative liver resection between 1991 and 2008; 127 had HCC without microscopic portal venous invasion, and 52 had HCC with microscopic portal venous invasion (MPVI). These two distinct groups were analyzed with regard to various clinicopathologic factors. Subsequently, we specifically investigated if HCCs 5 cm, the macroscopic appearance of HCC, and high levels of preoperative des-gamma-carboxyprothrombin are significant prognostic factors in identifying microvascular invasion of HCC. The strongest predictor of early recurrence (within 2 years) was the serum alpha-fetoprotein level in patients without clear microvascular invasion. CONCLUSIONS: Tumor size, macroscopic appearance, and high tumor marker levels are important elements in identifying the group of patients with a low HCC recurrence rate after curative liver resection

Simple simultaneous determination of soluble and insoluble trace metal components in sea salts by a combined coprecipitation/X-ray fluorescence method

An X-ray fluorescence method using the coprecipitation-preconcentration technique has been developed for simple determination of both acid-soluble and insoluble trace metal components, such as manganese, iron, nickel, copper and zinc in sea salts. A salt sample is dissolved in a nitric acid solution, and the residue is filtered off onto a membrane filter. After the pH is adjusted to 7-8, the filtrate is boiled, followed by addition of aluminum carrier, oxine and thionalide solutions. The solution is re-adjusted to pH 9, and kept at 80-85°C for 60 min. The precipitates are filtered off onto another membrane filter. X-Ray fluorescence intensities from two filters loaded with the residue and precipitates are measured and the concentrations of the elements are determined simultaneously using the calibration curves. Detection limits were 0.01 μg g-1 for manganese and copper. 0.04 μg g-1 for nickel and zinc, and 0.05 μg g-1 for iron, regardless of the soluble and the insoluble components. The present method was successfully applied to the analysis of sea salt samples

Update on targeted therapy and immune therapy for gastric cancer, 2018

Gastric cancer (GC) remains one of the most common cancers and serious health problems worldwide. For unresectable or metastatic advanced gastric cancer, chemotherapy treatment is first selected. Although chemotherapy has improved survival in patients with advanced gastric cancer (AGC), the prognosis of these patients remains poor. In recent years, some therapies targeting biological molecules have been reported to prolong the survival of patients with AGC. Since trastuzumab, a monoclonal antibody that targets HER2, was established as standard therapy for unresectable GC in a HER2-positive patient, many other targets have been reported as new therapy targets. Many molecular targeted therapies, such as HER2, VEGFR or EGFR, have been verified as established standard treatments with or without chemotherapy in clinical trials. Furthermore, immunotherapy is expected to be an effective treatment with promising clinical trial data. Especially, immune checkpoint inhibiters, such as PD-1/PD-L1 or CTLA-4, have demonstrated innovative progression in GC therapy. Moreover, ongoing clinical trials including targeted therapy and immunotherapy have shown promising results in improving clinical outcomes, safety, and tolerability. In this article, we review targeting therapies and immunotherapies for GC and summarize future prospective treatments

Prognostic Nutritional Index Predicts Outcomes of Gastrectomy in the Elderly

Background Owing to the increased life expectancy, elderly patients with gastric cancer is also increasing. Onodera\u27s prognostic nutritional index (PNI) is an assessment tool for nutritional status of surgical patients and possibly predicts prognosis of the patients. The aim of the present study is to clarify the predictive and prognostic significance of PNI in elderly patients who underwent gastrectomy for gastric cancer. Methods Two hundred ninety-five patients, including 196 nonelderly patients under 75 years old (group NE) and 99 elderly patients (group E), were eligible. We collected the data on nutritional status and the outcome of gastrectomy, including morbidity, mortality, and survival of these patients. A Cox proportional hazards model was used to evaluate the prognostic significance. Results The PNI was significantly lower in group E than in group NE. Both morbidity and mortality rates after gastrectomy were similar between the groups. Although PNI could not predict the postoperative events in group NE, low PNI might be a risk of mortality and morbidity in the elderly. Although survival after gastrectomy was similar among groups divided by the median PNI value (49.2) in group NE, the prognosis of PNI-L (<44.7) was significantly poorer than PNI-H (PNI≥44.7) in group E. Multivariate analysis demonstrated that PNI-L was an independent prognostic factor in the elderly. Conclusions The PNI predicts both short-term and longterm outcomes after gastrectomy in the elderly