[Effectiveness of between--hospital cooperation in staging laparoscopy].

INTRODUCTION: It is difficult to perform the staging of laparoscopy within the restricted time at a high-volume center. We thus started between-hospital cooperation as of April 2008. In this hospital cooperation, we perform surgery after laparoscopic examination at a cooperating hospital. MATERIALS AND METHODS: Staging laparoscopy was indicated for patients with T3 or T4 gastric cancer. These patients underwent staging laparoscopy at Maki Hospital before their scheduled surgery at our own hospital. RESULTS: Between April 2008 and January 2009, 14 patients underwent staging laparoscopy. We received the laparoscopic findings and confirmed the histopathological examination for median 11 days. The median duration from the day that we requested Maki Hospital to the day that patients underwent surgery was 34 days. No patient had laparoscopic complications. Of the 14 patients, 4 patients had peritoneal metastasis. Ten patients did not have peritoneal metastasis or positive cytology. Of these patients, 9 patients underwent surgery. R0 resection was achieved in 7 of 9 patients. False-negative results were obtained in two cases because of positive peritoneal cytology. CONCLUSION: Hospital cooperation may enable us to perform short-term staging laparoscopy. However, false-negative results were obtained in two cases because of positive peritoneal cytology. Further improvement must be made to assure the diagnostic accuracy of this procedure.

Feasibility and accuracy of second-look laparoscopy after gastrectomy for gastric cancer.

BACKGROUND: A better method for detecting early peritoneal progression is needed. This study evaluated the feasibility and accuracy of second-look laparoscopy for patients with gastric cancer treated using systemic chemotherapy after gastrectomy. METHODS: Second-look laparoscopy was conducted for patients who had no clinical evidence of distant metastases but had peritoneal metastases or positive peritoneal cytology results without visible metastatic disease at initial surgery, patients who underwent systemic chemotherapy over a 6-month period after surgery, and patients who had no clinical evidence of disease based on imaging study after completion of primary chemotherapy. RESULTS: Between November 2004 and April 2008, 21 patients underwent second-look laparoscopy. At the initial surgery, 13 of these patients underwent total gastrectomy and 8 patients underwent distal gastrectomy. One or two sheets of adhesion barrier were received by 18 patients. The median interval between initial surgery and second-look laparoscopy was 9.8 months (range, 6.6-17.5 months). All second-look procedures were completed laparoscopically, and no patients required conversion to laparotomy. None of the 21 patients experienced postlaparoscopy complications. Whereas 12 patients showed no pathologic evidence of disease, 9 patients showed disease at second-look laparoscopy. There was a significant difference in median survival between the groups with negative and positive results (p = 0.017). The median survival for the negative group has not been determined. All the patients in the positive group received further chemotherapy while showing a good performance status (PS). Six patients were PS 0, and 3 patients were PS 1. The median survival time for this group was 10.1 months. CONCLUSIONS: Second-look laparoscopy was a safe and promising approach to reassessment of peritoneal disease for patients with gastric cancer. The incidence of complications was low, particularly in this group of patients, all of whom had undergone prior gastrectomy.

Conjugated docosahexaenoic acid is a potent inducer of cell cycle arrest and apoptosis and inhibits growth of colo 201 human colon cancer cells.

The effect of conjugated docosahexaenoic acid (CDHA) on the inhibition of colon cancer cell growth was examined in the colo 201 human colon cancer cell line, and the effect was compared with docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). CDHA was a more potent tumor cell growth inhibitor than DHA and EPA by colorimetric 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay (IC50 for 72 h: 31.6 microM, 46.8 microM, and 56.6 microM, respectively). CDHA inhibited cell cycle progression, due to accumulation of cells in G1 phase, which involved increased p21Cip1/Waf1 and decreased cyclin D1, cyclin E, and proliferating cell nuclear antigen expression; the p53 and cyclin A levels were unchanged. Induction of apoptosis was confirmed by the appearance of sub-G1 populations, and apoptosis cascade involved upregulation of the apoptosis-enhancing proteins (Bak and Bcl-xS) and downregulation of the apoptosis-suppressing proteins (Bcl-xL and Bcl-2). CDHA modulated cell cycle regulatory proteins and apoptosis-related proteins, similar to the effects of DHA. CDHA at a dietary dose of 1.0% significantly inhibited growth of colo 201 cells transplanted in nude mice.

Comparison of intraperitoneal continuous infusion of floxuridine and bolus administration in a peritoneal gastric cancer xenograft model.

PURPOSE: To identify the optimal schedule for intraperitoneal (i.p.) infusion of floxuridine (FUDR) against peritoneal micrometastases from gastric cancer. METHODS: The efficacy of continuous i.p. infusion of FUDR was compared with that of bolus i.p. administration in peritoneal gastric cancer (MKN45) xenografts. The FUDR continuous delivery system in this study was in the form of injectable poly(lactic-coglycolic) acid (PLGA) microspheres intended for i.p. injection. Animals were treated by continuous i.p. infusion using FUDR-loaded microspheres or bolus i.p. administration of FUDR. RESULTS: In vitro testing demonstrated that FUDR was released slowly from the microspheres at a rate of approximately 5% of the total encapsulated drug per day. In in vivo studies, the peritoneal level was found to persist and was approximately 5- to 50-fold higher than that of plasma for more than 2 weeks following a single injection of the microspheres. An in vitro MTT assay showed that exposure time clearly influenced the cytotoxic potency of FUDR. In vivo, continuous infusion was more effective against peritoneal tumor than bolus administration at equivalent doses. However, compared with bolus administration, toxicity was increased, resulting in a reduced maximum tolerated dose (MTD) with continuous infusion. When the treatment was carried out at each MTD (continuous 1 mg/kg, bolus 600 mg/kg), continuous infusion had no advantage in inhibiting tumor growth. CONCLUSIONS: Owing to the higher toxicity and the equal efficacy of continuous infusion compared with bolus administration, continuous infusion is not recommended in i.p. FUDR treatment.

Trends in long-term survival following surgery for gastric cancer: a single institution experience.

We reviewed cases at our institution in an attempt to identify temporal trends in survival of patients with operable gastric cancer. We analyzed data on 1632 patients who received a diagnosis of gastric adenocarcinoma between 1975 and 1995 and who underwent surgery at our institution. The time trends were examined by comparing three time periods (1975-1984, 1985-1989 and 1990-1995). Over time there was an improvement in the R0 resection rate: the rate significantly increased from 65% to 83%. Short-term outcomes following surgery have improved, with 30-day mortality dropping from 3.5% to 1%. The overall survival curve continuously improved with time. The five-year survival rates improved from 43% to 61%. The increased use of extended lymph node dissection with careful examination for metastases allowed for more accurate TNM staging. The incidence of peritoneal failure remains high, with peritoneal recurrence observed in 49% of the patients who underwent R0 resection between 1985 and 1995 and who experienced recurrences. Our results demonstrated that current efforts to improve gastric cancer management are finally meeting with noticeable success. However, advanced-stage cancer remains a medical problem. Multimodal treatment of advanced disease will be an important theme in coming years.

Prepubertal resveratrol exposure accelerates N-methyl-N-nitrosourea-induced mammary carcinoma in female Sprague-Dawley rats.

The major object of this study was to characterize the effect of prepubertal trans-3,4',5-trihydroxystilbene (resveratrol) exposure on N-methyl-N-nitrosourea (MNU)-induced mammary carcinogenesis in female Sprague-Dawley rats. Prepubertal rats (15 to 19 days of age) were treated daily with either 10 or 100 mg/kg resveratrol for 5 days, and were compared with resveratrol-untreated animals (30 rats in each group). Six rats in each group were autopsied at 49 days of age, and their growth was evaluated. All remaining rats were given 50 mg/kg MNU, followed by monitoring for occurrence of mammary carcinoma. A dose of 100 mg/kg (but not 10 mg/kg) resveratrol significantly increased incidence of rat with mammary carcinomas > or =1 cm and multiplicity (all histologically detected mammary carcinomas per rat), but did not affect latency, compared with untreated controls. Resveratrol did not affect body weight increase, but 100 mg/kg resveratrol caused slightly earlier vaginal opening. Although all rats cycled, resveratrol-treated animals exhibited significantly increased irregularity of estrous cycle, spending more time in the estrus phase. Thus, short resveratrol treatment of prepubertal female rats affected endocrine function, and accelerated development of MNU-induced mammary carcinomas.

Effect of prenatal and prepubertal genistein exposure on N-methyl-N-nitrosourea-induced mammary tumorigenesis in female Sprague-Dawley rats.

BACKGROUND: The effect of prenatal and prepubertal genistein exposure on the development of chemically-induced mammary carcinomas in rat was investigated. MATERIALS AND METHODS: Genistein was subcutaneously (s.c.) injected daily, from gestational days 15 to 19, into pregnant Sprague-Dawley rats at 0, 1.5 or 30 mg/kg/day. Female offspring of mothers not exposed to genistein during pregnancy received daily s.c. injection, from prepubertal days 15 to 19, at a dose of 1.5 or 30 mg/kg/day. At 28 days of age, 6 female offspring from each group were sacrificed to observe the influence of genistein and the remaining rats were injected intraperitoneally with 50 mg/kg N-methyl-N-nitrosourea (MNU). Rats injected with MNU were sacrificed at 26 weeks of age or when their largest mammary tumor was > or = 1 cm in size. RESULTS: At the time when MNU was administered, the different groups had comparable mammary gland development; genistein-treated and -untreated rats had similar numbers of terminal end buds (TEBs) at the periphery of the mammary glandular tree. However, estrogen receptor alpha (ER alpha)- and progesterone receptor (PgR)-positive cells, p63-positive cells and proliferating cell nuclear antigen (PCNA)-labeling index were lower in genistein-exposed TEBs. Although tumor multiplicity and latency were not significant, prenatal or prepubertal genistein exposure, at low or high dosage, tended to suppress the incidence of mammary carcinomas > or = 1 cm; suppression was significant in the prepubertal low-dose group. CONCLUSION: The majority of the mammary carcinomas in the present study were hormone-dependent. The present findings suggest that administration of genistein in the perinatal period has protective effects against MNU-induced mammary carcinoma in Sprague-Dawley rats, via reduction of levels of ER alpha- and/or PgR-positive cells (presumed progenitor cells of mammary carcinomas), p63-positive mammary progenitor/stem cells (involved in cell renewal) and PCNA-positive cells (necessary for cell proliferation).

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

BACKGROUND: 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, < or = 25%; pN2, < or = 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.