Jong Sun Rew

Expression of tissue inhibitors of metalloproteinases (TIMPs) in gastric cancer.

Matrix metalloproteinases (MMPs) are one of the major classes of proteolytic enzymes involved in tumor invasion and metastasis, being inhibited by naturally occurring tissue inhibitors of metalloproteinases (TIMPs). Sixty-five patients who underwent surgery for gastric cancer in 1992 at Chonnam National University Hospital were selected for this study. The primary selection criteria were the availability of formalin-fixed and paraffin-embedded blocks and sufficient clinical follow-up for tumor-specific survival analysis. In this study, we examined the expression of TIMP-1 and TIMP-2 in human gastric cancer tissue by in situ hybridization and immunohistochemistry, and the correlation between their expression and clinicopathological parameters. TIMP-1 and TIMP-2 expressions were detected predominantly in the peritumor stromal cells rather than tumor cells themselves. Immunohistochemical stainings were concordant with the result obtained by in situ hybridization. The intensity of TIMP-1 immunohistochemical stromal staining correlated with tumor stage (P = 0.009) and patient survival (P = 0.025). However, the intensity of TIMP-2 immunohistochemical stromal staining did not correlate with tumor stage (P = 0.339) and patient survival (P = 0.474). The correlation between the increased TIMP-1 expression and cancer stage noted in this study reflects a role of TIMP-1 in predicting the aggressive behavior of gastric cancer. TIMP-2 expression did not correlate with clinicopathological parameters. However, expression of TIMP-1 and the possible additional value of TIMP-2 should be further explored in determining the prognosis of gastric cancer.

Epigallocatechin-3-gallate Inhibits LPS-Induced NF-κB and MAPK Signaling Pathways in Bone Marrow-Derived Macrophages

Background/Aims Epigallocatechin-3-gallate (EGCG), the primary catechin in green tea, has anti-inflammatory and anti-oxidative properties. The aim of the current study was to characterize the impact of EGCG on lipopolysaccharide (LPS)-induced innate signaling in bone marrow-derived macrophages (BMMs) isolated from ICR mice. Methods The effect of EGCG on LPS-induced pro-inflammatory gene expression and nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling was examined using reverse transcription-polymerase chain reaction, Western blotting, immunofluorescence, and the electrophoretic mobility shift assay. Results EGCG inhibited accumulation of LPS-induced IL-12p40, IL-6, MCP-1, ICAM-1, and VCAM-1 mRNA in BMMs. EGCG blocked LPS-induced IκBα degradation and RelA nuclear translocation. EGCG blocked the DNA-binding activity of NF-κB. LPS-induced phosphorylation of ERK1/2, JNK, and p38 was inhibited by EGCG. U0126 (an inhibitor of MEK-1/2) suppressed the LPS-induced IL-12p40, IL-6, MCP-1, ICAM-1, and VCAM-1 mRNA accumulation in BMMs. Conclusions These results indicate that EGCG may prevent LPS-induced pro-inflammatory gene expression through blocking NF-κB and MAPK signaling pathways in BMMs.

A Prospective Randomized Trial of Either Famotidine or Pantoprazole for the Prevention of Bleeding after Endoscopic Submucosal Dissection

Endoscopic submucosal dissection (ESD) has been reported to have a higher bleeding rate than conventional methods. However, there are few reports on whether a proton pump inhibitor or a histamine2-receptor antagonist is the more effective treatment for preventing bleeding after ESD. In a prospective trial, patients undergoing ESD due to gastric adenoma or adenocarcinoma were randomly assigned to pantoprazole or famotidine. Both drugs were given intravenously for the first 2 days, thereafter by mouth. Eighty-five in the pantoprazole group and 79 in the famotidine group were included for analysis. Primary outcome measure was the delayed bleeding rate. Clinical characteristics were not different between the two groups. The delayed bleeding rate was significantly lower in the pantoprazole group compared with the famotidine group (3.5% vs. 12.7%, p=0.031). On multivariate analysis, the preventive use of pantoprazole (relative hazard: 0.220, 95% CI: 0.051- 0.827, p=0.026) and the specimen size (≥34 mm, relative hazard: 4.178, 95% CI: 1.229-14.197, p=0.022) were two independent factors predictive of delayed bleeding. There were no significant differences in en bloc and complete resection rate between the two groups. In conclusion, pantoprazole is more effective than famotidine for the prevention of delayed bleeding after ESD.

Efficacy of low‐dose clarithromycin triple therapy and tinidazole‐containing triple therapy for Helicobacter pylori eradication

Proton pump inhibitor‐based triple therapies are recommended as the first‐line treatment for Helicobacter pylori eradication.

Expression of E- and N-cadherin and clinicopathology in hepatocellular carcinoma

Loss or reduced E‐cadherin expression and aberrant expression of N‐cadherin have been associated with invasiveness of human carcinoma cells and poor prognosis. The role of E‐ and N‐cadherin, however, in hepatocellular carcinoma (HCC) has not yet been elucidated. The aim of the present study was to investigate the expression pattern of E‐ and N‐cadherin in surgically resected HCC specimens according to their relationship with clinicopathological features. The expression patterns of E‐ and N‐cadherin were evaluated on immunohistochemistry in 68 specimens of HCC and adjacent non‐tumor tissue. The most different expression pattern between HCC and non‐tumor tissue was the decreased staining intensity of E‐cadherin (n = 37, 54%) and the dot‐like discontinuous staining of N‐cadherin (n = 35, 55%). Decreased intensity of E‐cadherin and discontinuous staining of N‐cadherin in HCC was correlated with advanced stage. The risk factors for expression patterns related to recurrence were loss of E‐cadherin expression (odds ratio (OR) = 3.6; 95% confidence interval (CI): 1.1–12.4) and discontinuous staining of N‐cadherin (OR = 1.6; 95% CI: 0.8–3.2). In conclusion, discontinuous staining of N‐cadherin and loss of E‐cadherin expression in HCC predicts a high risk of recurrence after surgical treatment.

The Role of Vascular Endothelial Growth Factor (VEGF) and p53 Status for Angiogenesis in Gastric Cancer

Background : Angiogenesis is of crucial importance for tumor growth and development of metastases. Vascular endothelial growth factor (VEGF) has a potent angiogenic activity and mutations of the p53 gene has been thought to upregulate VEGF. The purpose of our study was to evaluate the prognostic significance of these tumor biomarkers for angiogenesis relative to the information derived from established clinicopathological parameters in gastric cancer. Methods : In this study, we conducted an immunohistochemicai investigation of VEGF and p53 expression in 145 tissue samples obtained from gastric cancer patients undergoing curative surgical treatment. To evaluate angiogenesis, microvessel density (MVD) was counted by staining endothelial cells immunohistochemically using anti-CD34 monoclonal antibody. Results : High MVD was significantly associated with depth of tumor invasion and distant metastasis (p=0.004, 0.021, respectively). Moreover, overall survival for patients with high MVD were significantly lower than that of low MVD (p=0.048). Positive expression of VEGF correlated significantly with lymph node and distant metastasis (p=0.040, 0.048, respectively). However, no significant correlation was found between p53 expression and various clinicopathological parameters. VEGF positive tumors showed a higher MVD than VEGF negative tumors (p=0.028). The expression of p53 did not correlate with VEGF expression. Also, the relationship between the status of p53 expression and MVD had not statistically significant differences. In the multivariate analysis, status of VEGF, p53 expression and MVD were not an independent prognostic factor. Conclusion : VEGF seems to be an important, clinically relevant inducer of angiogenesis and angiogenesis assessed by the MVD may be a useful marker for predicting metastasis in gastric cancer. However, further studies are warranted to clarify the impact of p53 on the angiogenesis and the prognostic significance of angiogenesis in gastric cancer.

Epigenetic methylation and expression of caspase 8 and survivin in hepatocellular carcinoma

Caspase 8 and survivin are known as key molecules of apoptosis in hepatocellular carcinoma (HCC). The purpose of the present study was to investigate the relationship between promoter methylation and expression and apoptotic function of caspase 8 and survivin in HCC. Promoter methylation of the caspase 8 and survivin gene was analyzed in 73 primary HCC using methylation‐specific polymerase chain reaction. The relationship between immunohistochemical expression of gene products and proliferative/apoptotic indices, and clinicopathological parameters was also investigated. Twenty‐five (34%) and 24 (33%) patients had promoter methylation of caspase 8 and survivin gene. Immunohistochemical staining of caspase 8 and survivin was observed in 35 (48%) and 32 (44%). The methylation of caspase 8 and survivin demonstrated a negative correlation with immunohistochemical expression of gene products (P= 0.049 and P= 0.001). Methylation of caspase 8 and positive expression of its gene product was significantly correlated with high apoptotic indices (P= 0.032 and P= 0.026). Nuclear survivin expression was significantly correlated with high proliferative index (P= 0.001). On survival analysis, positive nuclear survivin expression was associated with a poor prognosis in HCC (P= 0.043). In conclusion, epigenetic alteration by promoter methylation of caspase 8 and survivin may constitute an important regulatory mechanism for expression of those genes in HCC.

Zollinger-Ellison syndrome associated with neurofibromatosis type 1: a case report.

BackgroundNeurofibromatosis type 1 is an autosomal dominant neurocutaneous disorder with characteristic features of skin and central nervous system involvement. Gastrointestinal involvement is rare, but the risk of malignancy development is considerable. Zollinger-Ellison syndrome is caused by gastrin-secreting tumors called gastrinomas. Correct diagnosis is often difficult, and curative treatment can only be achieved surgically.Case presentationA 41-year-old female affected by neurofibromatosis type 1 presented with a history of recurrent epigastric soreness, diarrhea, and relapsing chronic duodenal ulcer. Her serum fasting gastrin level was over 1000 pg/mL. An abdominal CT scan revealed a 3 × 2-cm, well-enhanced mass adjacent to the duodenal loop. She was not associated with multiple endocrine neoplasia type 1. Operative resection was performed and gastrinoma was diagnosed by immunohistochemical staining. The serum gastrin level decreased to 99.1 pg/mL after surgery, and symptoms and endoscopic findings completely resolved without recurrences.ConclusionGastrinoma is difficult to detect even in the general population, and hence symptoms such as recurrent idiopathic peptic ulcer and diarrhea in neurofibromatosis type 1 patients should be accounted for as possibly contributing to Zollinger-Ellison syndrome.

Gastric juice ammonia vs CLO test for diagnosis of Helicobacter pylori infection

The aim of the present study was to compare the gastric juice ammonia test to the CLO test for the diagnosis ofH. pylori infection in culture-proven cases by receiver operating characteristic (ROC) curve analysis. We studied 75 subjects (44 with chronic gastritis, 10 with gastric ulcer, 6 with duodenal ulcer, 8 with gastric cancer, and 7 normal) by endoscopy with biopsy for tissue diagnosis, culture ofH. pylori. CLO test, and by gastric juice ammonia determinations. The culture-positive group had significantly higher intragastric ammonia levels (13.7±5.8 mg/dl) than the negative group (4.9±2.4 mg/dl,P<0.01). In ROC curve analysis, the gastric juice ammonia test showed higher true positive and lower false positive ratios than the CLO test (P<0.05). In conclusion, the measurement of intragastric juice ammonia levels was considered to be simpler, quicker, and overall a more valuable method for diagnosingH. pylori infection.

Risk factors and clinical outcomes for spontaneous rupture of pyogenic liver abscess

To evaluate the risk factors and clinical outcomes in patients with spontaneous rupture of pyogenic liver abscess (PLA).