Gastric poorly cohesive carcinoma: a correlative study of mutational signatures and prognostic significance based on histopathological subtypes.

AIMS: Genome-wide next-generation sequencing has revealed several driver mutations and has allowed the establishment of a molecular taxonomy of gastric cancer. However, there are few detailed studies on the mutational spectrum of poorly cohesive gastric carcinoma. Thus, this study aim to investigate its mutation profile based on clinicopathological characteristics. METHODS AND RESULTS: Herein, we analysed the mutational pattern of 77 genes in a cohort of 91 patients with poorly cohesive carcinoma by using targeted sequencing, and evaluated the clinicopathological significance of the various mutations based on histological pattern, either signet ring cell (SRC) or other types of poorly cohesive carcinoma (not otherwise specified) (PCC-NOS). Panels of seven (PIK3CA, CDH1, PTEN, RHOA, HDCA9, KRAS, and ATM), three (PIK3CA, CTNNB1, and KRAS) and two (HDCA9 and IGF1R) genes were associated with a diffuse infiltrative growth pattern, lymphovascular invasion, and perineural invasion, respectively. Furthermore, PDGFRB mutations were associated with a favourable prognosis, whereas MET mutations were associated with a poor prognosis. The PCC-NOS-predominant type was associated with a greater depth of invasion, lymph node metastasis and poorer prognosis than the SRC-predominant type. Mutations in TP53, BRAF, PI3CA, SMAD4 and RHOA were associated with PCC-NOS. Interestingly, RHOA-mutated gastric cancers showed a distinct morphology, as they were characterised by a superficial SRC or tubular component and a deep invasive PCC-NOS component with desmoplasia. CONCLUSIONS: Taken together, our findings demonstrate that gastric poorly cohesive carcinomas show several mutational patterns associated with specific clinicopathological characteristics, and particularly show distinct morphological findings when associated with RHOA mutation.

Efficacy of insulin glargine in perioperative glucose control in type 2 diabetic patients.

BACKGROUND AND OBJECTIVE: Insulin glargine as a basal insulin exhibits constant absorption with no pronounced peaks in blood insulin levels and 24-h duration of action. We checked the effect of insulin glargine through the comparison of insulin glargine with glucose-insulin-potassium (GIK) on perioperative glucose control in insulin-treated type 2 diabetic patients. METHODS: Thirty insulin-treated type 2 diabetic patients, 40-80 years of age, were subjected to femoral artery bypass or knee amputation under general anaesthesia. The insulin glargine group (n = 15) was treated with insulin glargine (two-thirds of the total daily insulin dose required) subcutaneous administration with 5% dextrose solution infusion. The GIK group (n = 15) was treated with GIK infusion (125 ml h). Blood glucose levels were checked every 30 min during anaesthesia and 1 h after extubation. Potassium was checked every 1 h during anaesthesia and 2-4 h after extubation. Statistical analysis was performed with unpaired t test. RESULTS: There were no significant differences in the time course of blood glucose levels during operation and postoperative period between the two groups (P < 0.05). There was no hypoglycaemic episode in the perioperative period and no significant differences in potassium levels between the two groups. CONCLUSION: Insulin glargine was as effective as GIK regimen for perioperative glycaemic control during major surgery in insulin-dependent type 2 diabetic patients.

Reliability and validity of the Korean version of Kidney Disease Quality of Life instrument (KDQOL-SF).

Although the Kidney Disease Quality of Life instrument (KDQOL-SF), which was designed to measure the comprehensive quality of life in patients with end stage renal disease, has been tested and widely administered in many other counties, it has not yet been translated, validated and reported for Korea. The primary purpose of this study was to validate a Korean version of KDQOL-SF and to evaluate its psychometric properties. The study subjects were 164 patients with hemodialysis or continuous ambulatory peritoneal dialysis in university dialysis centers in Korea. In order to investigate the reliability, test-retest reliability and internal consistency reliability were assessed. Both test-retest reliability and internal consistency reliability were found to be high. In order to investigate the construct validation, all the items of the SF-36 scales, an established generic QOL measures, were compared with an overall health rating scale in kidney disease-targeted scale. They found to be highly correlated with each other. Moreover, overall health rating scale was significantly correlated with symptoms/problems, effects of kidney disease, burden of kidney disease, cognitive function (p < 0.001), and quality of social interaction (p < 0.05). These results suggest that the Korean version of KDQOL-SF satisfies its reliability and validity in Korean patients with hemodialysis or continuous ambulatory peritoneal dialysis. This questionnaire provides important and clinically valuable information for understanding the health related quality of life in the Korean patients with dialysis.