Postoperative evaluation of pylorus-preserving gastrectomy for early gastric cancer.

BACKGROUND/AIMS: There have been many reports proposing some advantages of pylorus-preserving gastrectomy for gastric ulcer compared to the conventional distal gastrectomy. However, it is not clear whether similar results will be obtained from the patients with early gastric cancer. METHODOLOGY: Of 50 patients with early gastric cancer, 25 underwent pylorus-preserving gastrectomy under strict criteria and the other 25 underwent distal gastrectomy with Billroth I anastomosis by the same surgeon. The subjects were then interviewed and examined periodically to assess symptoms, food intake, body weight and serum nutritional parameters. Endoscopy and a radioisotope gastric emptying test was performed 1 year after the operation. RESULTS: Many of the patients with pylorus-preserving gastrectomy complained of gastric fullness after meals, resulting in poor food intake; a significant between-group difference was found up to 1 year after the operation. A low incidence of reflux gastritis and slow gastric emptying were confirmed in the patients after pylorus-preserving gastrectomy. CONCLUSIONS: Pylorus-preserving gastrectomy has advantages over distal gastrectomy in terms of the avoidance of dumping syndrome and protection against duodeno-gastric reflux. However, more time was necessary for improved gastric fullness or food intake. Pylorus-preserving gastrectomy should be applied in younger patients with early gastric cancer expecting long survival.

MAP kinase-independent induction of proto-oncogene c-fos mRNA by hemin in human cells.

Treatment of HeLa cells or human skin fibroblast cells with hemin led to a time- and dose-dependent rapid induction of c-fos mRNA. This induction was absent in the cells treated with actinomycin D, indicating that the c-fos induction by hemin occurs at the level of transcription. Metalloporphyrins, including zinc-, cobalt-, and tin-protoporphyrin, ferric ion, and protoporphyrin also induced c-fos mRNA. Transient reporter assay with the reporter constructs of the human c-fos gene promoter up to -404 bp connected to the luciferase gene showed high activity but no induction by hemin, suggesting that cis-acting elements, including the serum response element located about -310 bp upstream of the human c-fos gene promoter, may not contribute to the heme-dependent induction. With in-gel assay of protein kinases, the activity of the mitogen-activated protein (MAP) kinases such as extracellular signal-regulated kinase 12 or p38 MAP kinase in hemin-treated HeLa cells was not stimulated. Stimulation of c-Jun N-terminal kinase by hemin was nil. Furthermore, PD58059 and SB203580, inhibitors for MAP kinases, did not affect the hemin-dependent c-fos induction. Of the inhibitors for protein kinases so far tested, KN-62, a specific inhibitor for calmodulin-dependent protein kinase II (CaMK II), inhibited the induction of c-fos mRNA by hemin. Phosphorylation of CaMK II in hemin-treated cells increased. With gel mobility assay, the DNA AP-1 binding activity transiently increased when treating HeLa cells with hemin. Therefore, induction of c-fos led to an activation of AP-1 in the presence of hemin. We suggest that calmodulin-dependent protein kinase II rather than the MAP kinase family regulates the induction of the human c-fos gene expression by hemin.

Cerebrospinal fluid nitric oxide metabolites in painful diseases.

To elucidate the involvement of NO in pain transmission in humans, we measured NO metabolites (nitrite/nitrate) in the CSF of patients with painful diseases using an NO analyzer based on the Griess method. The nitrite/nitrate levels in patients with degenerative lumbar disease (DLD), but not those with fracture or appendicitis, were significantly higher than those in an age-matched control group. The duration of pain in the DLD group was much longer than that in the fracture or appendicitis group. The nitrite/nitrate levels in the middle-aged and elderly DLD patients depended on the duration of pain. These data probably suggest that the duration of pain is critical for the elevation in nitrite/nitrate levels.

Incidence and prognosis of para-aortic lymph node metastasis in gastric cancer.

BACKGROUND/AIMS: We investigated the frequency of para-aortic lymph node involvement and evaluated the effects on survival of dissection of these lymph nodes in patients with N4 node metastasis. METHODOLOGY: One hundred and forty nine gastric cancer patients with N4 node dissection were analyzed. Total gastrectomy with splenectomy or pancreatosplenectomy was performed in 99, distal gastrectomy 48, pancreaticoduodenectomy 3, and proximal gastrectomy with splenectomy 2. RESULTS: N4 nodal involvement was found in about 30-40% of operable patients with Borrmann's type 3 or 4 tumor, with tumor >8 cm in size, with tumor throughout the entire or in the upper third of the stomach, with tumor invasion to the serosa or adjacent structures, with N2 or N3 regional lymph node metastasis, and with undifferentiated histological type. The survival was quite poor. However, in patients without N3 nodal involvement or intraperitoneal free cancer cells, the survival after resection of tumor with N4 nodal involvement was relatively favorable. CONCLUSIONS: The resection of these involved lymph nodes can be expected to be beneficial in patients without extensive serosal invasion and without extensive lymph nodal involvement such as N3 nodes. Patients with tumor in the upper third of the stomach are appropriate candidates for N4 node dissection.

Involvement of the tyrosine phosphorylation pathway in induction of human heme oxygenase-1 by hemin, sodium arsenite, and cadmium chloride.

The effect of a tyrosine kinase inhibitor, herbimycin A, on the induction of heme oxygenase-1 (HO-1) mRNA in HeLa cells upon exposure to hemin, sodium arsenite and cadmium chloride was examined. The induction of HO-1 mRNA by hemin was inhibited when the cells were pretreated with herbimycin A. Herbimycin also inhibited arsenite- and cadmium-dependent induction of HO-1 mRNA in a dose-dependent manner, but less inhibition was observed in cadmium-treated cells than in ones treated with hemin- or arsenite. Genistein (50 microM), another tyrosine kinase inhibitor, also inhibited the induction of HO-1 mRNA by hemin, arsenite, and cadmium. Nuclear runoff assays revealed that herbimycin blocked the hemin-induced transcription of the HO-1 gene. The induction of HO-1 mRNA by hemin in human peripheral blood mononuclear cells was inhibited by herbimycin. The tyrosine phosphorylation of a protein with a molecular mass of 66 kDa in the cells was increased by hemin- or arsenite-treatment, and this increase was inhibited by treatment with 5 microM herbimycin. When HeLa cells were treated with a specific inhibitor of the mitogen-activated protein kinase (MAPK)/extracellular-signal regulated kinase cascade, PD58059 (100 microM), suppression of the cadmium-dependent HO-1 induction was not observed, but the hemin- or arsenite-dependent induction was slightly inhibited. SB203580, an inhibitor of p38 MAPK, did not affect the HO-1 induction. These results indicated that signal transduction involving tyrosine kinase rather than the MAPK family regulates the induction of human HO-1 gene expression by stress inducers.