Koji Nakai

The superiority of ratio-based lymph node staging in gastric carcinoma

AbstractBackground: The need for a precise lymph node staging without stage migration is of paramount importance when comparing and evaluating international treatment results. Methods: We reviewed 1019 patients who underwent R0 resection at Kansai Medical University between 1980 and 1997. The patients were classified according to the 1997 International Union Against Cancer (UICC)/American Joint Committee on Cancer (AJCC) pN classification or the N staging depending on the ratio between the number of excised and the number of involved lymph nodes (pN1, ≤25%; pN2, ≤50%; pN3, >50%). Results: Among the 1997 UICC/AJCC pN subgroups, prognosis worsened with an increase in lymph node ratio. In contrast, the ratio-based classification showed more homogenous survival according to the number of involved lymph nodes. Multiple stepwise regression analysis showed that the ratio-based classification was the most significant prognostic factor, whereas the 1997 UICC/AJCC classification was not found to be an independent predictor of survival. In addition, the ratio-based classification showed a superiority to the 1997 UICC/AJCC classification with respect to stage migration. Conclusions: Ratio-based lymph node staging is simple and gives more precise information for prognosis with fewer problems related to stage migration than the 1997 UICC/AJCC staging system.

Cycloprodigiosin hydrochloride, H+/CL– symporter, induces apoptosis and differentiation in HL-60 cells

Cycloprodigiosin hydrochloride (cPrG • HCl), a novel H+/Cl– symporter, induces acidification of the cytosol and leads to apoptosis in rat and human liver cancer cells. In the present study, the effect of cPrG • HCl on a promyelocytic leukemia cell line (HL‐60) was examined. cPrG • HCl lowered intracellular pH and induced apoptosis through up‐regulation of Fas ligand, activation of stress‐activated protein kinase (SAPK/JNK) and caspase. Apoptosis induced by cPrG • HCl was strongly suppressed when a cell‐permeable weak base, imidazole, was present, indicating that cytosol acidification introduced by cPrG • HCl triggered caspase activation, leading to apoptosis. Concomitantly, cell differentiation into monocyte was also induced by cPrG • HCl both morphologically and functionally. However, the cPrG • HCl‐induced differentiation was not suppressed by addition of imidazole, indicating that the differentiation process is unrelated to cytosol acidification. Further, the differentiation induced by cPrG • HCl was blocked by tyrosine kinase inhibitors (lavendustin A and HMA) but unaffected by the inhibitors of A‐kinase (H‐89) or C‐kinase (H‐7). Taken together, these findings suggest that cPrG • HCl, through apoptosis and differentiation induction, may be useful in leukemia treatment. Int. J. Cancer 88:121–128, 2000.

Assessment of the preserved function of the remnant stomach in pylorus-preserving gastrectomy by gastric emptying scintigraphy

BackgroundThis study evaluated the preserved function of the remnant stomach by gastric emptying scintigraphy in patients who underwent pylorus-preserving gastrectomy (PPG), and it investigated whether this examination method is a useful tool for evaluation.Materials and MethodsThe residual stomach function was evaluated by gastric emptying scintigraphy in 45 patients with early gastric cancer who had undergone PPG. Function was classified as rapid, intermediate, and delayed emptying types according to gastric emptying curves. Then, the relationships were examined between the gastric emptying types and postprandial symptoms, food intake status, body weight changes, and endoscopic findings.ResultsSeventy-three percent of the PPG patients were classified as belonging to the intermediate emptying type, and the remainder to the delayed emptying type. The frequencies of complaints such as epigastric fullness, nausea, and vomiting were high in the delayed emptying-type patients. The intermediate emptying-type patients consumed larger amounts of food and gained more weight than the delayed emptying-type patients. It was difficult to estimate gastric emptying function from endoscopic findings.ConclusionsGastric function was evaluated by gastric emptying scintigraphy in PPG patients. This method might be useful not only for evaluating the motor function of the remnant stomach, but also for predicting postoperative status.

Synergistic Effects Induced by Cycloprodigiosin Hydrochloride and Epirubicin on Human Breast Cancer Cells

The effects of cPrG·HCl and epirubicin on the suppression of cell growth were examined on human breast cancer cell line (MDA-MB-231). Either cPrG·HCl or epirubicin alone showed a tumor growth inhibition in a time- and dose-dependent manner, however, the combinatory use of cPrG·HCl together with epirubicin resulted in prominent synergistic effects on the breast cancer cells. In the in vitro studies, the combinatory use of these two drugs accelerated apoptotic cell death as revealed by morphological changes as well as by the appearance of subG1 population by flow cytometry. In addition, confocal microscopy revealed that the accumulation of epirubicin in nucleus increased apparently when cPrG·HCl were present. In the in vivo assay, nude mice bearing xenografted tumor cells received 4 weeks of intraperitoneal administration of cPrG·HCl and epirubicin. After 12 days, the combinatory treatment significantly suppressed the tumor growth compared to the controls. The TUNEL staining revealed that tumor cells in cPrG·HCl plus epirubicin-treated mice exhibited a higher apoptotic rate. In addition, 31P-NMR studies on the xenografted tumor revealed that cPrG·HCl lowered tumor pHi (below pH 6.9), while it did not affected muscle pHi. No pathological changes were observed in any intrinsic organs and the serum alanine aminotransferase levels remained within normal limits among the groups. These results suggest that the combinatory use of cPrG·HCl and epirubicin may be useful for breast cancer therapy.

Effect of epidermal growth factor on intestinal adaptation after allogeneic small bowel transplantation in rats.

We reported that epidermal growth factor (EGF) stimulated graft adaptation in a rat model of syngeneic small bowel transplantation. However, graft rejection is a severe problem with clinical small bowel transplantation, because small intestinal wall contains large amounts of lymphoid tissue. Studies were performed to investigate the effect of EGF on allogeneic graft adaptation after small bowel transplantation in rats treated with an immunosuppressant FK506. The transplanted animals received intraperitoneally EGF or saline (untreated) after surgery and were examined for analysis one week later. EGF-treated group markedly enhanced the water absorption and induction of sodium glucose cotransporter (SGLTI) as compared with EGF-untreated group. EGF-treated group also increased the mucosal crypt depth and its cell proliferating rate, although there was no significant difference in the mucosal villus height between the two groups. These results indicate that EGF accelerates intestinal allograft adaptation in part by the recovery of mucosal structure and function after small bowel transplantation in rats. EGF may have relevance to promote graft function in clinical small intestinal transplantation.

Surgical Control of a Primary Hepatic Carcinoid Tumor: A Case Report.

We report a primary hepatic carcinoid tumor occurring in a 47-year-old man. The patient consulted our hospital complaining of epigastralgia. Abdominal ultrasonography, computed tomography scanning, and magnetic resonance imaging showed a large mass in the right lobe of the liver. FDG-PET revealed 18F-FDG uptake by the right hepatic lobe. The tumor was a solid mass with cystic components, approximately 15 cm in diameter. We conducted an extended right lobectomy of the liver. The resected specimen was a solid tumor with cystic components and hemorrhagic lesion. Microscopic findings showed that the tumor cells had round nuclei and formed trabecular patterns. Immunohistologically, tumor cells were stained positive for chromogranin A, neuron specific enolase, CD56, and S-100. Careful examinations before and after the operation revealed no other possible origin of the tumor. Based on these findings, the tumor was diagnosed as a primary hepatic carcinoid. This is a report of a rare case of a primary hepatic carcinoid tumor with a discussion of several other relevant reports.

Posterior Esophagopexy with Dome Formation to Prevent Reflux in Interposed Jejunal Pouch Reconstruction After Total Gastrectomy

Jejunal pouch interposition (JPI) reconstruction after total gastrectomy has proven effective for improving postoperative quality of life; however, evaluation of bile reflux into the esophagus shows that the reflux of digestive juice is not sufficiently prevented. Therefore, in addition to the conventional reconstruction technique, we created an artificial pouch to prevent the reflux of digestive juice from the jejunal pouch into the esophagus, and performed a new surgical technique based on the Hills posterior gastropexy. No postoperative complications were observed and the postoperative measurement showed a decrease in the duration of bile reflux into the esophagus. Thus, our new surgical procedure seems to effectively prevent bile reflux.