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Hepatocellular carcinoma (HCC) occurs mainly in the liver associated with chronic hepatitis and hepatic cirrhosis as a result of prolonged viral infection. Transforming growth factor-beta (TGF-beta) induces the fibrosis in hepatic cirrhosis, although it is also an inhibitor of hepatocyte proliferation. To understand the role of TGF-beta signaling in HCC progression, we analyzed gene expression in HCC cells in relation to TGF-beta signaling using a two-way clustering algorithm. By the analysis, five HCC cell lines were classified into two groups according to their metastatic capacity. TGF-beta receptor II (TGFBR2) was downregulated in metastatic cells, which did not show a response to TGF-beta. Immunohistochemistry demonstrated clear membrane distribution of TGFBR2 in noncancerous hepatocytes, whereas reduced TGFBR2 expression was observed in 34 of 136 HCCs. In clinical cases, reduced TGFBR2 expression correlated with larger tumor size (P

Aims: We retrospectively assessed the benefits of 5-fluorouracil (5-FU)-and heparin-based portal infusion chemotherapy combined with systemic administration of mitomycin C (MMC) and cisplatin (CDDP) for 4 weeks following surgery (PI4W). The goal was to determine if this treatment prevented liver metastasis and improved survival for patients with potentially curative resection of pancreatic cancer. Methods: 68 patients who underwent pancreatectomy from January 1995 to August 2007 were treated. Of these cases, 22 patients received portal infusion with 5-FU (250 mg/day) for 2 weeks (PI2W) following surgery, while 25 patients received PI4W therapy (250 mg/day of 5-FU with 2,000 IU/day of heparin everyday for 4 weeks, 4 mg MMC on days 6, 13, 20, 27, and 10 mg CDDP on days 7, 14, 21, 28). The remaining 21 patients were treated without adjuvant therapy during the perioperative period. Results: All patients except one completed the portal infusion chemotherapy without toxicity. The cumulative liver metastasis-free survival rate in the PI4W group was significantly higher than those in the other two groups. Furthermore, in the PI4W group, 3-year survival was 91.6% and 5-year survival was 70.5%, rates which were significantly better than those observed in the other two groups. Conclusion: PI4W therapy after surgery is feasible and could become a promising adjuvant therapy in patients with potentially curative resection of pancreatic cancer.

Background Surgical site infection (SSI) is an important clinical indicator of quality of patient care and infection control; therefore, we aimed to assess risk factors SSI in colon and gastric surgeries. Methods SSI was assessed according to the National Nosocomial Infection Surveillance (NNIS) system (1999). Risk factors examined included operative approach, operative procedure, duration of operation, diabetes mellitus (DM), body mass index (BMI), age, and sex. Results Among 3152 operated patients, 1675 patients were included in the study. The univariate analysis showed that male sex, high BMI, and long duration of operation were significant risk factors for colon surgery and that advanced age, presence of DM and long duration of operation were significant risk factors for gastric surgery. The multivariate analysis indicated that significant risk factors for SSI were BMI of 25 or above, open surgery, and long duration of operation for colon surgery and open surgery for gastric surgery. The SSI rate of laparoscopic colon surgery was 40%, less than that of open colon surgery, and that of laparoscopic gastric surgery was 75%, less than that of open gastric surgery. Conclusion The risk factors for SSI depend on whether the operation is laparoscopic or open and duration of operation. In addition, BMI (25 or above) and age (70 years or above) are risk factors for colon and gastric surgery, respectively.

Background Removal of the primary lesion with a clear operative margin is the standard treatment for gastrointestinal stromal tumor (GIST) of the stomach. However, there are few reports on the operative indications for relatively small GIST. Methods Clinicopathologic features and survival data of all 60 patients with GIST of the stomach treated at Keio University Hospital from 1993 to 2004 were analyzed. Laparoscopic wedge resection was used as the primary procedure for tumors between 2 to 5 cm. Tumors larger than 5 cm were resected by laparotomy or laparoscopy-assisted operation. Results Thirty-five lesions (58.3%) were resected by laparoscopic wedge resection, 3 by laparoscopic operation with a small skin incision and 22 by conventional open procedures. The mean size of the tumors was 42.5 mm, with a range of 18 to 150 mm and a median value of 35.5 mm. All operative margins were clear, but 1 patient had liver metastases at the time of resection of the primary lesion. The median follow-up period was 53 months and the 5-year disease-free survival rate (DFS) was 96.1%. No local recurrence or distant metastasis was encountered in patients with tumors smaller than 4 cm. A statistically significant correlation was observed between tumor size and mitotic count in this cohort ( P = .010). Tumors from the intermediate- (n = 14) and high-risk (n = 10) groups as classified by the Risk Assessment Classification showed significantly worse DFS than the low-risk and very low risk group (n = 35) (89.9% vs 100% in 5-year DFS, P = .045). Even among tumors smaller than 3 cm, 2 of 14 cases (14.3%) were classified into the intermediate-risk group. Conclusions Although a prospective randomized trial remains to be performed, this study provides additional evidence suggesting that the early removal of GIST, at 5 cm or less in size, provides better DFS than later removal of the tumor at a larger size.

Surgical site infection (SSI) surveillance was examined in gastric cancer patients who had undergone an open gastrectomy between 1997 and 2003 at Keio University Hospital in Tokyo, Japan. National Nosocomial Infections Surveillance (NNIS) reports and several studies have discussed SSI risk factors, but only open gastrectomy was analyzed by regression analysis. The purpose of this study was to examine these issues by performing a regression analysis for the prediction of SSI. SSI was defined by the surgical patient component according to the NNIS system (1999) produced by the Centers for Disease Control and Prevention. Patients undergoing an open gastrectomy were followed up and monitored for SSIs. Risk factors for SSI, after all factors were considered, were studied using single and multivariate analysis. The study enrolled 984 patients who had undergoing an open gastrectomy. Using multivariate and logistic regression analysis, the duration of the operation was identified as a [corrected] risk factor for SSI at open gastrectomy. Although numerous potential risk factors in surgical patients were examined, the duration of the operation was the only significant risk factor for SSIs after open gastrectomy.

Establishing a method to control peritoneal dissemination is one of the most pressing issues in the postsurgical treatment of pancreatic cancer. In the present study, we investigated the effect of dendritic cell (DC)-based immunotherapy on peritoneal disseminations of hamster pancreatic cancer cells, PGHAM-1. After the orthotopically inoculation of 2×10 6 PGHAM-1 cells, DC pulsed with PGHAM-1-derived tumor lysates, DC alone or PBS as a vehicle was injected intraperitoneally (i.p.) three times at weekly intervals. The group treated with DC or DC+lysate was found to have smaller disseminated tumors than the vehicle-treated. In addition, mean survival time in the DC+lysate groups was significantly longer than the PBS group. These findings suggested that DC-based immunotherapy might be efficient for the treatment of peritoneal disseminations of the pancreatic cancer.

Background . The presence of tumor cells in the blood stream is considered evidence of a high risk of distant organ metastasis. We examined the usefulness of telomerase activity in peripheral blood polymorphonuclear cells as an indicator of distant metastasis in patients with esophageal squamous cell carcinoma. Methods . Telomerase activity was measured in the peripheral blood mononuclear cell and polymorphonuclear cell fractions obtained from blood samples of healthy volunteers mixed with squamous cell carcinoma cell lines, and cell distribution was analyzed by flow cytometry. Then telomerase activity of forty-two polymorphonuclear cell fractions obtained from esophageal squamous cell carcinoma patients was measured. Results . Telomerase activity was detected in polymorphonuclear cell fractions and cell distribution analysis revealed the presence of esophageal squamous cell carcinoma cells. Organ metastasis was detected in 7 (78%) of the 9 patients with telomerase-positive polymorphonuclear cell fractions as opposed to only five (15%) of the 33 with telomerase-negative cases, and there was a significant positive correlation between telomerase activity and organ metastasis ( p Conclusions . Measurement of telomerase activity in the polymorphonuclear cell fractions is useful for identifying a high risk group for distant organ metastasis in patients with esophageal squamous cell carcinoma.

Recombinant human ribonuclease 1 (RNase 1) was chemically linked to recombinant human epidermal growth factor (EGF). The EGF-RNase conjugate showed dose-dependent cytotoxicity for EGF receptor-overexpressing A431 and TE-8 human squamous carcinoma cells with an IC50 of 2 x 10(-7)M and 10(-6)M, respectively, whereas the IC50 of RNase alone was almost 10(-4)M. An unconjugated mixture of EGF and RNase had no greater effect than RNase alone. The conjugate showed no detectable cytotoxicity against EGF receptor-deficient small cell lung cancer cells (H69). Addition of excess EGF in the medium protected A431 cells from the EGF-RNase conjugate cytotoxicity. The cytotoxicity of the EGF-RNase conjugate was positively correlated with the EGF receptor numbers of each cell line. The chimeric toxin composed of only human proteins might be a more useful anti-cancer agent with less immunogenicity than the conventional chimeric toxins.