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OBJECTIVES Accurate preoperative prediction of the prognosis of patients with invasive ductal carcinoma of pancreatic head (pancreatic head cancer) is important for selecting treatment methods. We retrospectively examined the prognostic predictive values of endoscopic ultrasound (EUS) findings for patients with this disease. METHODS The subjects were 66 patients with pancreatic head cancer who had undergone EUS. We examined each EUS finding as a possible prognostic predictor, including heterogeneity of internal echo, irregularity of peripheral echo, clarity of boundary echo, dilatation of the main pancreatic duct (MPD), dilatation of the common bile duct, lymph node swelling, vessel invasion, and the presence of ascites, by univariate and multivariate analysis for survival. RESULTS Irregular peripheral echo, portal vein invasion, superior mesenteric artery/celiac artery invasion, and the presence of ascites were significant predictors of a poorer prognosis by univariate analysis for survival. In resectable cases, EUS findings of MPD dilatation and portal invasion were significant prognostic predictors by univariate analysis, and MPD dilatation was an independent prognostic predictor by multivariate analysis. CONCLUSION EUS may be useful for predicting the prognosis of patients with pancreatic head cancer, based on the accuracy it provides in evaluating locoregional spreading.

Objective: S-1 is a novel oral fluorouracil antitumor drug that combines three pharmacological agents: tegafur (FT), a prodrug of 5-fluorouracil (5-FU); 5-chloro-2,4-dihydroxypyridine (CDHP), an inhibitor of dihydropyrimidine dehydrogenase, and potassium oxonate (Oxo), a reducer of gastrointestinal toxicity. S-1 has safe and potent antitumor effects in patients with gastric cancer via these respective functions. However, the plasma 5-FU concentration is suspected to accumulate in patients with renal dysfunction, because 50% of the CDHP is excreted into the urine. There are no useful data on safety and efficacy of S-1 in chronic renal failure patients maintained on hemodialysis (HD). We examined the influence of HD on the pharmacokinetics (PK) of S-1 and its therapeutic efficacy in liver metastases from gastric cancer. Methods: For the HD patient, the dose of S-1 in a single-administration study was set at 50 mg/body/day (41.7% of the recommended dose of 80 mg/m2/day). S-1 was given to the patient 24 h after HD. Blood samples were obtained before administration and 2, 4, 6, 8, and 24 h thereafter and 1, 2, 4, and 72 h after the following HD session. The PK parameters (5-FU, CDHP, Oxo, and FT) were measured, and Cmax, Tmax, AUC0–24, and T1/2 were calculated. The dose of consecutive or maintained administrations was determined. Results: Both an increase in Cmax and an elongation of T1/2 for 5-FU, CDHP, and Oxo, but not for FT, occurred in this case as compared with controls. The AUC0–24 of 5-FU in this case was similar to that of controls at the standard dose. After HD, 87.8, 54.5, 77.4, and 66.2% of 5-FU, CDHP, Oxo, and FT, respectively, were eliminated. A slight accumulation of CDHP did not alter the 5-FU PK. Consecutive or maintained S-1 oral administration at the same dose showed similar effects on all PK parameters of a single-administration test. Liver metastases almost totally regressed with no adverse events 4 weeks after S-1 treatment (50 mg/body/day three times a week). Conclusion: Adjusted doses of S-1 according to the results of PK studies may provide therapeutic safety and high efficacy in liver metastases from gastric cancer, even in chronic renal failure patients maintained on HD.

Activator protein-1 (AP-1), a transcription factor, is activated through many oncogenic signals. However, its biological role in colorectal cancer has not been fully elucidated. To investigate the role of AP-1 in colorectal cancer, we constructed an adenovirus-expressing TAM67, a dominant-negative mutant of c-Jun lacking the transactivation domain of wild c-Jun (DN-c-Jun), to inhibit endogenous AP-1. AP-1 DNA-binding activity was increased in colon cancer cells (HT-29 cells) by serum stimulation, followed by an increase in both [(3)H]thymidine incorporation and cell number. Transfection of Ad-DN-c-Jun to HT-29 cells significantly inhibited serum-induced cell proliferation in vitro. As shown by flow cytometric analysis, DN-c-Jun significantly inhibited entrance into S phase after serum stimulation, thereby leading to G(1) arrest. In vivo transfection of Ad-DN-c-Jun into xenografted HT-29 cell tumors in nude mice significantly decreased tumor volume on day 21 after treatment. A change was associated with decrease in Ki-67 labeling index. These observations together showed that AP-1 is a critical modulator for proliferation and cell cycle of HT-29 cells. We obtained the first evidence that DN-c-Jun gene transfer exerted a significant antitumor effect on colon cancer both in vitro and in vivo. DN-c-Jun gene transfer may be a new candidate for treatment of colorectal cancer.