Yeon Myung Shin

p16INK4a Promoter hypermethylation of non-tumorous tissue adjacent to gastric cancer is correlated with glandular atrophy and chronic inflammation

The p16INK4a tumor suppressor gene can be inactivated by promoter region hypermethylation in many tumor types including gastric cancers. However, p16INK4a promoter hypermethylation in the surrounding non‐tumorous tissues of gastric cancers has not been studied in detail. We therefore examined 46 gastric cancers, corresponding adjacent non‐tumorous tissue samples and 8 gastric tissue samples of chronic gastritis by performing methylation‐specific polymerase chain reaction, and we analyzed p16INK4a protein expression using immunohistochemistry and Western blot. p16INK4a promoter hypermethylation was observed in 43% of gastric cancers and 59% of adjacent non‐tumorous tissues; however, none of the samples retrieved from the chronic gastritis patients displayed p16INK4a promoter hypermethylation. Gastric cancers showed an inverse correlation between vascular invasion and p16INK4a promoter hypermethylation, and adjacent non‐tumorous tissues displayed a close association among the grade of chronic inflammation, presence of glandular atrophy and p16INK4a promoter hypermethylation. p16INK4a expression was markedly decreased in samples with p16INK4a promoter hypermethylation when compared with samples without p16INK4a promoter hypermethylation. These results suggest that p16INK4a promoter hypermethylation is an early and frequent event in gastric carcinogenesis and may serve as a new prognostic biomarker for the risk of gastric cancers.

Prediction of nephrotoxicity induced by cisplatin combination chemotherapy in gastric cancer patients

AIM To evaluate the treatment options for nephrotoxicity due to cisplatin combination chemotherapy. METHODS We retrospectively reviewed patients who had received cisplatin combination chemotherapy for gastric cancer between January 2002 and December 2008. We investigated patients who had shown acute renal failure (ARF), and examined their clinical characteristics, laboratory data, use of preventive measures, treatment cycles, the amount of cisplatin administered, recovery period, subsequent treatments, and renal status between the recovered and unrecovered groups. RESULTS Forty-one of the 552 patients had serum creatinine (SCR) levels greater than 1.5 mg/dL. We found that pre-ARF SCR, ARF SCR, and ARF glomerular filtration rates were significantly associated with renal status post-ARF between the two groups (P = 0.008, 0.026, 0.026, respectively). On the receiver operating characteristic curve of these values, a 1.75 mg/dL ARF SCR value had 87.5% sensitivity and 84.8% specificity (P = 0.011). CONCLUSION Cessation or reduction of chemotherapy should be considered for patients who have an elevation of SCR levels during cisplatin combination chemotherapy.

Correlation between HER2 Overexpression and Clinicopathological Characteristics in Gastric Cancer Patients Who Have Undergone Curative Resection.

Purpose At present, a human epidermal growth factor receptor 2 (HER2)-based concept of tumor biology has been established, and trastuzumab (Herceptin®; Genentech/Roche, San Francisco, CA, USA), a monoclonal humanized antibody directed against HER2, is a pivotal agent for the management of HER2 positive (HER2+) metastatic breast cancer. It is also known that HER2 has a predictive value in gastric cancer; however, its association with the prognosis of this disease remains uncertain. The purpose of this study was to evaluate both the relationship between HER2 overexpression in the tumors of gastric cancer patients, and the prognosis of these patients who have had curative resection. Materials and Methods A total of 139 consecutive patients with gastric cancer who underwent surgery at the Kosin University Gospel Hospital between October 2011 and March 2012 were included in this retrospective study. All tumor samples were examined for HER2 expression by immunohistochemistry. A retrospective review of the medical records was conducted to determine the correlation between the presence of HER2 overexpression and clinicopathological factors. Results The HER2+ rate was 15.1%. HER2 overexpression was associated with histological grade (P=0.044) and Lauren classification (P=0.036). There was no significant difference in the 2-year overall survival between HER2+ and HER2- patients (P=0.396). Multivariate analysis showed that HER2 was not an independent prognostic factor. Conclusions HER2 overexpression in tumors was associated with histological grade and Lauren classification in gastric cancer patients with curative resection. However, HER2 was not an independent prognostic factor for gastric cancer in our study.

Amylase, lipase, and volume of drainage fluid in gastrectomy for the early detection of complications caused by pancreatic leakage

Purpose Pancreatic leakage is a serious complication of gastrectomy due to stomach cancer. Therefore, we analyzed amylase and lipase concentrations in blood and drainage fluid, and evaluated the volume of drainage fluid to discern their usefulness as markers for the early detection of serious pancreatic leakage requiring reoperation after gastrectomy. Methods From January 2001 to December 2007, we retrospectively analyzed data from 24,072 patient samples. We divided patients into two groups; 1) complications with pancreatic leakage (CG), and 2) no complications associated with pancreatic leakage (NCG). Values of amylase and lipase in the blood and drainage fluid, volume of the drainage fluid, and relationships among the volumes, amylase values, and lipase values in the drainage fluid were evaluated, respectively in the two groups. Results The mean amylase values of CG were significantly higher than those of NCG in blood and drainage fluid (P < 0.05). For lipase, statistically significant differences were observed in drainage fluid (P < 0.05). The mean volume (standard deviation) of the drained fluid through the tube between CG (n = 22) and NCG (n = 236) on postoperative day 1 were 368.41 (266.25) and 299.26 (300.28), respectively. There were no statistically significant differences between the groups (P = 0.298). There was a correlation between the amylase and lipase values in the drainage fluid (r = 0.812, P = 0.000). Conclusion Among postoperative amylase and lipase values in blood and drainage fluid, and the volume of drainage fluid, the amylase in drainage fluid was better differentiated between CG and NCG than other markers. The volume of the drainage fluid did not differ significantly between groups.

Prevalence of Malnutrition in Hospitalized Patients: a Multicenter Cross-sectional Study.

Background Malnutrition is associated with many adverse clinical outcomes. The present study aimed to identify the prevalence of malnutrition in hospitalized patients in Korea, evaluate the association between malnutrition and clinical outcomes, and ascertain the risk factors of malnutrition. Methods A multicenter cross-sectional study was performed with 300 patients recruited from among the patients admitted in 25 hospitals on January 6, 2014. Nutritional status was assessed by using the Subjective Global Assessment (SGA). Demographic characteristics and underlying diseases were compared according to nutritional status. Logistic regression analysis was performed to identify the risk factors of malnutrition. Clinical outcomes such as rate of admission in intensive care units, length of hospital stay, and survival rate were evaluated. Results The prevalence of malnutrition in the hospitalized patients was 22.0%. Old age (≥ 70 years), admission for medical treatment or diagnostic work-up, and underlying pulmonary or oncological disease were associated with malnutrition. Old age and admission for medical treatment or diagnostic work-up were identified to be risk factors of malnutrition in the multivariate analysis. Patients with malnutrition had longer hospital stay (SGA A = 7.63 ± 6.03 days, B = 9.02 ± 9.96 days, and C = 12.18 ± 7.24 days, P = 0.018) and lower 90-day survival rate (SGA A = 97.9%, B = 90.7%, and C = 58.3%, P < 0.001). Conclusion Malnutrition was common in hospitalized patients, and resulted in longer hospitalization and associated lower survival rate. The rate of malnutrition tended to be higher when the patient was older than 70 years old or hospitalized for medical treatment or diagnostic work-up compared to elective surgery.

A Promising Method for Tumor Localization during Total Laparoscopic Distal Gastrectomy: Preoperative Endoscopic Clipping based on Negative Biopsy and Selective Intraoperative Radiography Findings

Purpose Precise localization of tumors and creation of sufficient proximal resection margins are complicated processes during total laparoscopic distal gastrectomy (TLDG) for clinical T1/T2 gastric cancers. Various solutions to this problem have also yielded many disadvantages. In this study, we reviewed a preoperative endoscopic clipping method based on the results of negative biopsy and selective intraoperative radiography. Materials and Methods A retrospective review of 345 consecutive patients who underwent TLDG and preoperative endoscopic clipping for tumor localization was conducted. During preoperative endoscopy, the endoscopists performed negative biopsies just 1–2 cm selectively above the tumors upper limit. After confirming the biopsy results, endoscopic metal clips were applied just proximal to the negative biopsy site the day before surgery. Selective intraoperative tumor localization using portable abdominal radiography was performed only when we could not ensure a precise resection line. Results Negative biopsy was performed in 244 patients. Larger tumor size (P=0.008) and more distally located tumors (P=0.052) were observed more frequently in the negative biopsy group than in the non-negative biopsy group. The non-negative biopsy group had significantly higher frequencies of differentiated tumor types than the negative biopsy group (P=0.003). Of the 244 patients who underwent negative biopsies, 6 had cancer cells in their biopsy specimens. We performed intraoperative radiography in 12 patients whose tumors had difficult-to-determine proximal margins. No tumors were found in the proximal resection margins of any patients. Conclusions Our tumor localization method is a promising and accurate method for securing a sufficient resection margin during TLDG.