Management of gastric epithelial neoplasia in patients requiring esophagectomy for esophageal cancer.

Esophageal squamous cell carcinoma is occasionally associated with malignancies located in other regions of the alimentary tract, as well as in the head, neck, and upper respiratory tract. The stomach is most commonly used for reconstruction of the alimentary tract after esophagectomy for esophageal cancer. When synchronous tumors are located in the stomach, it is often unsuitable for use in esophageal reconstruction. In such cases, an invasive procedure involving anastomosis between the esophagus and the colon must be performed. However, this procedure is associated with a high incidence of mortality and morbidity. Seven patients with synchronous esophageal cancer and gastric epithelial neoplasia were encountered. First, endoscopic submucosal dissection (ESD) was performed for the gastric epithelial neoplasia. Then, following successful ESD, Ivor-Lewis esophagectomy for esophageal cancer was planned 1 to 2 weeks later. A total of 11 gastric epithelial lesions were found in seven patients. En bloc resection by ESD was possible in all 11 lesions and histologically complete resection was achieved in all 11 lesions. Follow-up endoscopy was done 1-2 weeks after ESD; six patients with well-healing ulcers underwent esophagectomy the next day (8 or 15 days after ESD). In one patient with a poorly healed ulcer, a second follow-up endoscopy was done 1 week later and then esophagectomy was performed the next day (22 days after ESD). Post-surgical complications related to ESD, such as bleeding or mediastinal leak, were not seen in any of the seven patients. In patients with synchronous esophageal cancer and gastric epithelial neoplasia, ESD for gastric epithelial neoplasia followed by Ivor-Lewis esophagectomy 1 to 2 weeks later is an effective choice of treatment.

Endoscopic submucosal resection of esophageal subepithelial lesions using band ligation.

Subepithelial lesions (SELs) are occasionally found in the esophagus during upper endoscopy. Sometimes endoscopic resection is needed for accurate diagnosis or in the rare cases of malignant transformation of SELs. In this case series, we evaluated the usefulness of endoscopic submucosal resection with a ligation device (ESMR-L) in esophageal SELs. Twenty-three patients with 25 esophageal SELs that were no larger than 13 mm and were localized within the muscularis mucosae or submucosa were enrolled. ESMR-L was successfully performed in all 25 SELs. The en bloc resection rate was 100% (25/25), and histologically complete resection was achieved in 24 lesions (24/25, 96%). After resection of the lesion by snare, minor immediate bleeding occurred in four cases, but there was no delayed bleeding or perforation.

Overexpression of stathmin1 in the diffuse type of gastric cancer and its roles in proliferation and migration of gastric cancer cells.

BACKGROUND: Stathmin1 is a microtubule-regulating protein that has an important role in the assembly and disassembly of the mitotic spindle. The roles of stathmin1 in carcinogenesis of various cancers, including prostate and breast cancer, have been explored. However, its expression and roles in gastric cancer have not yet been described. METHODS: Stathmin1 expression in paraffin-embedded tissue sections from 226 patients was analysed by immunohistochemistry. Roles of stathmin1 were studied using a specific small interfering RNA (siRNA). RESULTS: The expression of stathmin1 was positively correlated with lymph node metastasis, TNM stages and vascular invasion, and negatively with recurrence-free survival, in the diffuse type of gastric cancer. The median recurrence-free survival in patients with a negative and positive expression of stathmin1 was 17.0 and 7.0 months, respectively (P=0.009). When the expression of stathmin1 was knocked down using siRNA, the proliferation, migration and invasion of poorly differentiated gastric cancer cells in vitro were significantly inhibited. Moreover, stathmin1 siRNA transfection significantly slowed the growth of xenografts in nude mice. CONCLUSION: These results suggest that stathmin1 can be a good prognostic factor for recurrence-free survival rate and is a therapeutic target in diffuse-type gastric cancer.

Smad4 expression in gastric adenoma and adenocarcinoma: frequent loss of expression in diffuse type of gastric adenocarcinoma.

Smads are signal transducers for the members of the TGF-beta superfamily. Of these Smads, Smad4 is essential for TGF-beta signaling. The purpose of this study was to elucidate Smad4 expression and localization in 65 gastric adenomas, 49 intestinal-type and 39 diffuse type of gastric adenocarcinomas (including 12 cases of fresh frozen tissue) using Real-time RT-PCR and immunohistochemistry. Real-time RT-PCR showed that intestinal type gastric adenocarcinomas have higher Smad4 mRNA expression than diffuse type gastric adenocarcinomas. Immunohistochemical stain for Smad4 revealed that expression of Smad4 was significantly lower in diffuse-type gastric adenocarcinoma than intestinal-type gastric adenocarcinomas. Also, higher Smad4 protein expression in intestinal type gastric adenocarcinomas than overall gastric adenoma was noted. The rate of reduced Smad4 expression was higher in advanced gastric cancer than early gastric cancer. These results suggest that Smad4 might play different roles in human gastric carcinogenesis, especially between intestinal type and diffuse type of gastric adenocarcinoma.

Which types of stent, uncovered or covered, should be used in gastric outlet obstructions?

BACKGROUND: Self-expandable metallic stents (SEMS) have been widely used in inoperable malignant gastric outlet obstructions, but stent obstructions caused by tumor ingrowth and migration are a major problem of SEMS. The aims of this study were to assess the rate of stent restenosis, to identify lesion characteristics related to early restenosis by tumor ingrowth, and, in particular, to find suitable patient groups for uncovered or covered stents at first implantation. METHODS: Forty-nine patients were reviewed: stomach cancer in 34 patients, primary duodenal cancer in 3 patients, pancreatic cancer in 5 patients, and common bile duct cancer in 7 patients. In principle, uncovered stents were initially placed at the time when obstruction symptoms occurred and the endoscope would not pass through. Stent obstruction due to tumor ingrowth within 4 weeks after the first stent implantation was regarded as early stent restenosis. RESULTS: Technical success was seen in 49/49 patients (100%). Migration did not occur. Stent obstructions caused by tumor overgrowth were found in 2/49 patients (4.1%) after 1 month. Stent obstructions caused by tumor ingrowth occurred in 14/49 patients (28.5%), and 7 of them (14.3%) were found to have early restenosis. The only statistically significant factor for early restenosis was stenosis site, and early restenosis was more frequent in the postoperative anastomosis site in the current study; a) 2/18 antropyloric obstructions (11.1%), b) 1/15 pyloric and duodenal bulb obstructions (6.7%), c) 0/10 duodenal second portion obstructions (0%), and d) 4/6 postoperative anastomosis site obstructions (66.7) (P < 0.05, 95% CI 0.003-0.005). CONCLUSIONS: Uncovered stents are technically feasible and effective for most malignant gastric outlet obstructions. However, because of frequent early restenosis among patients with postoperative anastomosis site obstructions, the placement of covered or simultaneous dual stents to prevent early restenosis should be considered when stenting postoperative anastomosis site obstructions.

Antiperistaltic ileostomy using the long terminal ileal segment.

PURPOSE: This study was undertaken to determine whether reversed terminal ileal segments can be used to decrease ileostomy output in patients who have undergone total proctocolectomy and ileostomy for ulcerative colitis or familial adenomatous polyposis. METHODS: An approximately 25-cm length of terminal ileum was reversed in an antiperistaltic manner, and the new terminal ileal end was used for the ileostomy constructed in the usual manner. Six patients underwent this procedure and were compared with six patients who had conventional total proctocolectomy and ileostomy. Variables studied included weight of ileostomy output and the weight of the filtered fluid component. Data were obtained on seven different occasions during a two-month period beginning three months after the operation. Analysis was done using Student's t-test. RESULTS: There was a statistically significant decrease in the weight of the average 24-hour ileostomy effluent in those patients undergoing reversed antiperistaltic loop procedures. There was also a statistically significant decrease in the filterable liquid proportions. CONCLUSIONS: The antiperistaltic ileostomy is effective in reducing the daily amount of ileostomy effluent and facilitates stoma care, owing to its diminished liquid component.

Effect of Ca2+ channel blockers, external Ca2+ and phospholipase A2 inhibitors on t-butylhydroperoxide-induced lipid peroxidation and toxicity in rat liver slices.

OBJECTIVES: This study was undertaken to examine the effect of oxidant on lipid peroxidation and lethal cell injury in rat liver slices. METHODS: t-Butylhydroperoxide (t-BHP) was employed as a model of an oxidant. The lipid peroxidation and lethal cell injury were estimated by measuring the formation of malondialdehyde (MDA) and lactate dehydrogenase (LDH) release, respectively. RESULTS: t-BHP increased lipid peroxidation and LDH release in a dose-dependent manner over concentrations of 0.5-10 mM. t-BHP-induced lipid peroxidation was completely prevented by an antioxidant, N,N-diphenyl-p-phenylenediamine (DPPD), but LDH release was partially decreased. Both t-BHP-induced lipid peroxidation and LDH release were significantly protected by iron chelator, deferoxamine, sulfhydryl reducing agent, dithiothreitol and glutathione. Ca2+ channel blockers, verapamil, diltiazem and nifedipine exerted a significant protective effect against t-BHP-induced lipid peroxidation and LDH release. By contrast, addition of external Ca2+ chelator, ethylene glycol bis(b-aminoethyl ether)-N,N-tetraacetic acid (EGTA) did not alter t-BHP-induced lipid peroxidation, whereas t-BHP-induced lethal cell injury was significantly prevented. Phospholipase A2 (PLA2) inhibitors, mepacrine and butacaine produced a partial protective effect. CONCLUSIONS: These results suggest that t-BHP induces cell injury by lipid peroxidation-dependent and -independent mechanisms which can be partially prevented by Ca2+ channel blockers and PLA2 inhibitors.