Upgrade of Lesions Initially Diagnosed as Low-Grade Gastric Dysplasia upon Forceps Biopsy Following Endoscopic Resection

BACKGROUND/AIMS: Gastric dysplasia is generally accepted to be the precursor lesion of gastric carcinoma. Approximately 25% to 35% of histological diagnoses based on endoscopic forcep biopsies for gastric dysplastic lesions change following endoscopic resection (ER). The aim of this study was to determine the predictive endoscopic features of high-grade gastric dysplasia (HGD) or early gastric cancer (EGC) following ER for lesions initially diagnosed as low-grade dysplasia (LGD) by a forceps biopsy. METHODS: To determine predictive variables for upgraded histology (LGD to HGD or EGC). The lesion size, gross endoscopic appearance, location, and surface nodularity or redness as well as the presence of a depressed portion, Helicobacter pylori infection, and intestinal metaplasia were retrospectively investigated. RESULTS: Among 251 LGDs diagnosed by an initial forceps biopsy, the diagnoses of 100 lesions (39.8%) changed following the ER; 56 of 251 LGDs (22.3%) were diagnosed as HGD, 39 (15.5%) as adenocarcinoma, and 5 (2.0%) as chronic gastritis. In a univariate analysis, large lesions (>15 mm), those with a depressed portion, and those with surface nodularity were significantly correlated with a upgraded histology classification following ER. In a multivariate analysis, a large size (>15 mm; odds ratio [OR], 2.8; 95% confidence interval [CI], 1.46 to 5.43) and a depressed portion in the lesion (OR, 2.7; 95% CI, 1.44 to 5.03) were predictive factors for upgraded histology following ER. CONCLUSIONS: Our study shows that a substantial proportion of diagnoses of low-grade gastric dysplasias based on forceps biopsies were not representative of the entire lesion. We recommend ER for lesions with a depressed portion and for those larger than 15 mm.

Effect of Helicobacter pylori Infection on p16, p53, CEA, EGFR Expression in Gastric Neoplasia

BACKGROUND/AIMS: Gastric cancer is one of the most widespread cancers and the second leading cause of cancer-related death worldwide. Although Helicobacter pylori (H. pylori) has been classified as a type I carcinogen for gastric cancer, the exact pathway has remained indistinct. In this study, we investigated the effects of H. pylori on oncogenic proteins (epidermal growth factor receptor [EGFR], CEA), tumor suppressor (p53) and cell-cycle regulator (p16) expression, using immunohistochemical stains, in gastric neoplasias. MATERIALS AND METHODS: From April 2007 until July 2009, 166 patients with consecutive gastric neoplasias resected were retrospectively enrolled; 35 gastric dysplasias, 70 early gastric cancers and 60 advanced gastric cancers. We examined the relationship of clinicopathologic features of gastric neoplasias such as age, sex, p16, p53, EGFR, tissue CEA, TNM stage, Lauren classification, location, histologic type of neoplasia to H. pylori infection status. RESULTS: H. pylori infection detected in the samples of gastric dysplasia, early gastric cancer (EGC) and advanced gastric cancer (AGC) were 15 (41.7%), 38 (54.3%) and 33 (55.0%) samples. p53, CEA and EGFR stains expression were associated with cancer stage (P<0.05). There was no relation between the immunohistochemical stains (p16, p53, CEA, EGFR) and H. pylori infection. CONCLUSIONS: This study failed to show any relation of immunohistochemical markers of p16, p53, EGFR, CEA expressions to H. pylori infection in gastric dysplasia as well as gastric cancer. Further study is necessary to investigate the effect of H. pylori infection on p16, p53, CEA, EGFR expressions in precancerous lesions such as atrophic gastritis and intestinal metaplasia.

Dobutamine stress echocardiography for evaluating cirrhotic cardiomyopathy in liver cirrhosis / 대한간학회지

BACKGROUND/AIMS: The blunted ventricular systolic and diastolic contractile responses to physical and pharmacological stress in cirrhosis are termed cirrhotic cardiomyopathy (CCM). CCM has been known to involve multiple defects in the beta-adrenergic signaling pathway. The aim of this study was to determine whether cirrhotic patients have blunted cardiac responses to catecholamine stimulation through dobutamine stress echocardiography (DSE). METHODS: Seventy-one cirrhotic patients with normal left ventricular (LV) chamber size and ejection fraction were enrolled. The LV systolic and diastolic functions were evaluated by two-dimensional and Doppler echocardiography at rest and during peak dobutamine infusion (40 microg/kg/min). An abnormal response was defined as a decrease of less than 10% in LV end-diastolic volume, a decrease of less than 20% in end-systolic volume, and an increase of less than 10% in LV ejection fraction (EF) at peak dobutamine infusion, based on previously used criteria. The early/late diastolic flow (E/A) ratio and diastolic parameters were also measured. RESULTS: A blunted LV response to dobutamine was observed in 18 of 71 cirrhotic patients (25.4%). The baseline EF was significantly higher in 18 patients with a blunted DSE response than that of those with a normal DSE response (P<0.05). The baseline and peak E/A ratios, which are common diastolic dysfunction markers, were higher in the cirrhosis group than in the control group (P<0.001). No adverse events associated with DSE were observed. CONCLUSIONS: Blunted cardiac responses to dobutamine stimulation, which are implicated in defects in the beta-adrenergic signaling pathway, might contribute to the pathogenesis of CCM in patients with cirrhosis.

Stool Based DNA Biomarkers for Colorectal Cancer Diagnosis

Colorectal cancer (CRC) is a leading cause of cancer incidence and death worldwide. CRCs develop from morphologic transformation of normal colon epithelium to neoplasia thorough a sequential accumulation of genetic or epigenetic events. This slow carcinogenic process enables the diagnosis of CRC at earlier stages if the adequate screening strategies are feasible. In practice, recent researches have provided a technical tool for the detection of an early disease by a selective combination of noninvasive biomarkers using stool DNA, which may lead to cure the disease effectively. However, these noninvasive biomarkers for CRC screening should have acceptable sensitivity with high specificity in order to prevent unnecessary colonoscopies and consequent risks. Stool based DNA biomarkers can be used with ease and lead to greatly enhance screening acceptance. Identification of noble genetic and epigenetic DNA molecules selectively derived from colorectal neoplasia in stool can be in the forefront of CRC screening by becoming an optimal and affordable means of early detection as well as prevention of CRC in the general population.

Beneficial Effects of Thiazolidinediones on Diabetic Nephropathy in OLETF Rats

PURPOSE: Diabetic nephropathy is the most serious of complications in diabetes mellitus. Thiazolidinedione (TZD) is thought to ameliorate diabetic nephropathy; however, the mechanism underlying this effect has not been elucidated. We hypothesized that the vascular endothelial growth factor (VEGF) participates in the pathogenesis of diabetic nephropathy and that TZD may be beneficial for the treatment of diabetic nephropathy because of the effect it has on VEGF. MATERIALS AND METHODS: 23 Otsuka- Long-Evans-Tokushima-Fatty (OLETF) rats and eight control Long-Evans-Tokushima-Otsuka (LETO) rats were divided into the following four groups: LETO group, control OLETF group, pioglitazone treated group (10mg/kg/day), and rosiglitazone treated group (3mg/kg/day). RESULTS: A progressive increase in urinary protein excretion was observed in the diabetic rats. Glomerular VEGF expression in the control OLETF rats was significantly higher than in the control LETO rats. However, there was a significant reduction in both the glomerular VEGF expression and the VEGF mRNA levels after treatment with pioglitazone and rosiglitazone. The twenty-four hour urine protein levels were significantly decreased in both groups of the treated OLETF rats. CONCLUSION: These results suggest that TZD may have beneficial effects on diabetic nephropathy by reducing the VEGF expression.

Predictive Factors of Recurrent Bleeding in Mallory-Weiss Syndrome / 대한소화기학회지

BACKGROUND/AIMS: Although the majority of patients with Mallory-Weiss syndrome (MWS) have a benign course, MWS patients with recurrent bleeding have an unfavorable outcome and require intensive care. Therefore, this study was carried out to identify the risk factors for recurrent bleeding in MWS patients. METHODS: The medical records of patients with MWS between January 1999 and December 2003, were reviewed retrospectively. Demographics, initial clinical and laboratory parameters, and endoscopic findings of the patients with and without recurrent bleeding were compared and the potential risk factors predicting recurrent bleeding in MWS were evaluated. RESULTS: A total of one hundred and fifty-nine patients (22 women, 137 men, mean age 48.1 years old) were enrolled in the study. Recurrent bleeding was observed in 17 patients (10.7%). Those patients with recurrent bleeding showed higher frequency for the presence of shock at initial manifestation, combined liver cirrhosis and endoscopic findings of active bleeding, lower hemoglobin level and platelet count, higher amount of transfusions and epinephrine-mixed fluid injections, and longer hospital stay than those patients without recurrent bleeding. Significant risk factors predicting the recurrent bleeding in MWS were the presence of shock at initial manifestation (OR 3.71, 95% CI 1.07-14.90) and the evidence of active bleeding on endoscopic examination (OR 9.89, 95% CI 1.88-51.98) on multivariate analysis. CONCLUSIONS: Intensive care with close monitoring is required for the patients with shock on initial manifestation or with evidence of active bleeding on endoscopic examinations since these are independent risk factors predicting the recurrent bleeding in MWS patients.