Influence of CYP2C19 Polymorphism and Helicobacter pylori Status on the Antisecretory Effect of Omeprazole in Gastroesophageal Reflux Disease / 대한소화기학회지

BACKGROUND/AIMS: The acid suppressive effect of omeprazole (OMP) is influenced by the metabolic capacity of gastric acid suppression, which is dependent on CYP2C19 polymorphism. The aim of this study was to determine the influence of CYP2C19 polymorphism and Helicobacter pylori (H. pylori) infection on the intragastric acid suppression of OMP. METHODS: Thirty one patients with gastroesophageal reflux disease were treated with a daily oral dose of 20 mg OMP for 28 days. Patients were genotyped for CYP2C19 polymorphism by polymerase chain reaction-restriction fragment length polymorphism and classified into three groups: homogenous extensive metabolizers (Ho-EMs), heterogenous extensive metabolizers (Ht-EMs) and poor metabolizer (PMs). H. pylori infection status were assessed before OMP treatment. Intragastric pH was monitored over twenty four-hours before (day 0) and after (day 29) the treatment with OMP. RESULTS: Twenty four-hour intragastric mean pH in the PMs group was significantly higher than those in Ho-EMs and Ht-EMs (5.3+/-1.3 vs. 2.8+/-0.6, 3.6+/-1.4) (p<0.005). Twenty four-hour intragastric mean pH after the administration of OMP in the H. pylori positive group was significantly higher than the H. pylori negative group (4.7+/-1.4 vs. 3.2+/-1.4) (p<0.001). There was no significant difference in acid suppressive activity of OMP between H. pylori positive and negative group according to CYP2C19 polymorphism. CONCLUSIONS: The acid suppressive effect of OMP on intragastric pH is dependent on CYP2C19 polymorphism and the H. pylori-infected status in patients with gastroesophageal reflux disease. H. pylori infection may play a role in enhancing the acid suppressive potential of OMP.

A Case of Multiple Bleeding Pseudoaneurysms Complicating Acute Pancreatitis / 대한소화기학회지

Arterial pseudoaneurysm is rare but potentially a catastrophic complication of pancreatitis because it can cause massive gastrointestinal bleeding. Since surgical treatment of arterial pseudoaneurysm has a high mortality, percutaneous angiographic embolization of bleeding artery has recently been advocated as the alternative therapy. Acute hemorrhage into the peritoneal cavity or pseudocyst complicating chronic pancreatitis was frequently reported. However, multiple pseudoaneurysmal hemorrhage without pseudocyst complicating acute pancreatitis are extremely rare. Here, we present a case of multiple pseudoaneurysmal hemorrhage secondary to acute pancreatitis, which were managed successfully by percutaneous angiographic embolization.

Expression of iNOS in Accordance with the Subtypes of Intestinal Metaplasia / 대한내과학회지

BACKGROUND: Intestinal metaplasia (IM) type 3 has been suggested to be associated with gastric cancer of intestinal type. Excess nitric oxide (NO) has been reported to be associated with pathogenesis of various diseases, including gastric cancer. This study measured isoform nitric oxide synthase (iNOS) expression immunohistochemically to examine the possible involvement of NO in the subtypes of intestinal metaplasia. METHODS: The subjects were 71 male and 35 female cases. To classify the IM subtypes, the specimens were stained with alcian blue pH 2.5/PAS and high iron diamine/alcian blue pH 2.5. The expression of iNOS was assessed by means of immunohistochemical stain using polyclonal anti-iNOS antibody. RESULTS: IM type 1 was diagnosed in 42 cases (39.6%), IM type 2 in 42 cases (39.6%), and IM type 3 in 22 cases (20.8%). As the subject become older, the frequency of IM type 3 increased significantly. The expression of iNOS was increased significantly as the subtype was developed into type 3. However, there was no significant difference in the iNOS expression by the existence of sulphomucin, age, positivity of Helicobacter pylori, or biopsy site. CONCLUSION: Increased expression of iNOS in the IM type 3 suggests that IM type 3 is a possible risk factor for gastric cancer.

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 immunohistochemical 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.

Expression of Vascular Endothelial Growth Factor and p53 in Pancreatic Carcinomas

BACKGROUND: Angiogenesis has been shown to be a critical aspect of tumor growth and progression. Vascular endothelial growth factor (VEGF) has potent angiogenic activity and has been identified in a wide variety of malignancies, including pancreatic carcinoma. The tumor-suppressor gene p53 has been thought to regulate VEGF in angiogenesis. The aim of the current study was conducted to investigate the association between p53 mutation and VEGF expression and the prognostic value of these factors in pancreatic carcinoma. METHODS: Formalin-fixed, paraffin-embedded tissue specimens were obtained from 30 patients who underwent surgery for pancreatic carcinoma. We used an immunohistochemical technique to localize VEGF and p53 in pancreatic carcinoma tissues. RESULTS: Positive expression of VEGF was detected in 17 out of 30 (56.7%) tumors. Positive expression of VEGF correlated with the depth of tumor invasion (p=0.002). There was a trend towards an association between positive expression of VEGF and distant metastasis, although these associations were not statistically significant (p=0.070). p53 mutations were identified in 18 out of 30 (60.0%) tumors. However, no significant correlation was found between p53 expression and various clinicopathological parameters. The correlation between p53 mutation and VEGF expression was statistically significant (p=0.004). CONCLUSION: VEGF, a key factor for the induction of tumor-associated angiogenesis, may be involved in tumor characteristics, including tumor invasion and metastasis. And p53 mutation may be implicated in the regulation of angiogenesis through a VEGF up-regulation.

A Case of Peutz-Jeghers Syndrome with Multiple Intussusception and Rectal Adenocarcinoma / 대한소화기내시경학회지

Peutz-Jeghers syndrome (PJS) is a rare disease of autosomal dominant inheritance, which is characterized by hamartomatous gastrointestinal polyps and mucocutaneous melanin pigmentation. PJS often presents as surgical emergen cies with complications of the polyps, such as intussusception, small bowel obstruction, bleeding and volvulus. Intussusception caused by PJS polyps is often observed in the small bowel, but intussusception which involving small and large bowel concommittantly is not so much. The association between PJS and an increased risk for cancer has been controversial. Recent studies have shown PJS have a increased risk for both gastrointestinal and extraintestinal cancer. We report a case of PJS with rectal adenocarcinoma and multiple intussusceptions involving small and large bowel concommittantly.