Involvement of oxidative stress in experimentally induced reflux esophagitis and esophageal cancer.

BACKGROUND/AIMS: Recent studies have demonstrated that refluxed duodenal contents cause esophageal carcinoma in rats without exposure to carcinogens. Oxidative damage has long been related to carcinogenesis in human cancers and animal cancer models. The purpose here was to investigate the pathogenesis of esophageal cancer in the experiment of chronic duodenal content reflux without carcinogen. METHODOLOGY: Thirty 8-week-old male Wistar rats were exposed to duodenal content esophageal reflux. All animals underwent an esophagoduodenal anastomosis (EDA) with total gastrectomy in order to produce chronic esophagitis. In 10 rats the sham operation induced a midline laparotomy alone (Control). A total of 37 of 40 (92.5%) rats completed the study. In the EDA group, 27 (90%) rats completed the study. In the control group, 10 (100%) rats completely the study. They were sacrificed at the 35th week. Their esophagi were examined for the presence of cancer, Barrett's esophagus (BE), columnar line epithelium (CLE) and oxidative stress. RESULTS: After 35 weeks of reflux, columnar dysplasia and squamous carcinoma were found. PCNA labeling index was higher in dysplastic and cancer tissue than that of normal. To discover the role of oxidative stress and radical scavenger capacity in the malignant transformation of Barrett's esophagus, we measured Malondialdehyde (MDA), Superoxide dismutase (SOD) activity and Glutathione (GSH) content in EDA rats. Mucosal MDA levels were significantly increased in EDA groups compared with the normal controls. GSH and SOD levels were significantly decreased in EDA group compared with the normal control group. CONCLUSIONS: We proposed that oxidative damage plays an important role in the formation of esophageal cancer with EDA model.

Clinicopathologic significance of expression of cyclooxygenase-2 in human esophageal squamous cell carcinoma.

BACKGROUND/AIMS: The focus of studies on cyclooxygenase-2 (COX2) have been on its ability to mediate the biological behavior of human tumors including tumorigenesis, tumor progression, apoptosis and differentiation. The aim of the current study was to elucidate a further finding on the clinicopathologic significance of immunohistochemical expression of COX2 in esophageal squamous cell carcinoma. METHODOLOGY: The immunohistochemical expression of COX2 was examined for 68 specimens of esophageal squamous cell carcinoma (ESCC) and the correlation of COX2 expression with clinicopathologic features was examined. COX2 immunoreactivity was weak in 27 (40%) and strong in 41 (60%) of the carcinomas. RESULTS: The proportion of poorly differentiated SCCs among tumors with a strong expression of COX2 (34%, 14 of 41) was significantly higher than among tumors with a weak expression of COX2 (19%, 3 of 14, p = 0.02). The depth of the tumors (p = 0.0004), lymph node metastasis (p = 0.009) and the stage of the tumors (p = 0.001) were advanced significantly more progressively in ESCCs with a strong COX2 expression. Moreover, survival was significantly reduced (p = 0.02) among patients with strong COX2 expression when compared with the COX2 weak group. CONCLUSIONS: This study showed that strong expression of COX2 was correlated with tumor progression and poor differentiation in ESCC.

Duodenogastric reflux after choledochoduodenostomy: evaluation by technetium-99m scintigraphy.

BACKGROUND/AIMS: Persistence of dyspeptic symptoms after choledochoduodenostomy (CDD) is common. There is evidence that at least some of these symptoms may be attributed to duodenogastric reflux (DGR). The aim of the study was to quantify DGR after CDD. METHODOLOGY: A total of 6 patients who had undergone cholecystectomy with a standard side-to-end CDD for choledocholithiasis or Lemmel syndrome were studied by symptom evaluation, biliary scintigraphy and endoscopy at least 6 months after surgery. Duodenogastric reflux was quantified using continuous intravenous infusion of 99mTc-HIDA. RESULTS: The incidence of DGR after CDD was 67% compared to healthy control. In the majority of the patients the DGR was mild to moderate, but not with the clinical symptoms. CONCLUSIONS: 99mTc-HIDA scanning of the hepatobiliary system is a reasonable and reliable method for the quantitative evaluation of DGR. CDD is associated with a high incidence of DGR, but its occurrence does not produce significant clinical symptoms.

[TS-1 was prescribed for a patient with stomach cancer with peritoneal dissemination who survived for 3 years and 2 months].

A 42-year-old female patient underwent total gastrectomy for gastric cancer (Borrmann's Type 3). Many rice-grain sized peritoneal metastases were observed in the transverse colon and mesenterium. The lesion was diagnosed as stage IV cancer and the degree of radical cure was determined to be C. Chemotherapy with TS-1 was administered postoperatively. In each cycle, the drug was administered at a daily dose of 100 mg for 4 weeks, followed by a drug-free period of 2 weeks. The adverse reactions were mild, and she underwent the 2nd and further courses of therapy on an outpatient basis. Since she had acute cholecystitis during the 12th course, the drug was withdrawn for 2 months. Thereafter, the drug was started again after resolution of the cholecystitis. At present, ie, 3 years and 2 months after the surgery, the patient is receiving the 23rd course of chemotherapy on an outpatient basis, and abdominal CT shows no evidence of increase in the peritoneal metastases, enlargement of the intraperitoneal lymph nodes, or ascites.