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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.

Background: Mitogen-activated protein (MAP) kinases, including extracellular signal-regulated kinases (ERK), c-Jun NH 2 -terminal kinases (JNK) and p38 MAP kinase (p38 MAPK) are important intermediates of the signal-transduction pathway from the cell surface to the nucleus. Expression of cyclooxygenase (COX)-2, associated with proliferation, apoptosis or both of gastrointestinal cancer cells, is mediated through MAP kinase families. However, the correlation between respective MAP kinase signals and COX-2 in the proliferation of gastric and colon cancer cells has not been well elucidated. Aim: We examined the effect of selective inhibitors of MAP kinases and COX-2 on serum-induced proliferation of gastric (MKN45) and colon (HT29) cancer cells. Methods: After 24-h serum starvation, cancer cells were stimulated with 2% serum and COX-2 inhibitors (NS398 10 μmol/L, or etodolac 100 μmol/L) or 1 h after preincubation with inhibitors for ERK (PD98059 20 μmol/L) or p38 MAPK (SB203580 10 μmol/L). Phosphorylated MAP kinases and COX-2 protein were evaluated by Western blotting, and the proliferation of cancer cells was estimated by 3 H-thymidine incorporation. Transcription factors nuclear factor-KB and CREB were assayed by an electorophoretic mobility shift assay. Results: Serum increased the proliferation of MKN45 and HT29 cells by 280% and 200%, respectively, compared with the control levels (100%). In both cancer cells, phosphorylated MAP kinases were increased within 30 min after stimulation. PD98059 and SB203580 inhibited the serum-induced proliferation of MKN45 by 21% and 51% and of HT29 by 81% and 69%, respectively. NS398 and etodolac inhibited the proliferation of HT29 by 21% and 41%, respectively, but not that of MKN45. PD98059 and SB203580 also suppressed serum-induced expression of COX-2 protein in HT29 cells. In addition to the activation of MAP kinases and COX-2, activities of nuclear factor-KB and CREB were also increased during HT29 cell proliferation. Conclusions: These results suggest that the correlation of MAP kinases with COX-2 induction for cell proliferation differs between MKN45 and HT29 cells.

Endoscopic ultrasonography-guided fine-needle aspiration biopsy (EUS FNAB) is a relatively new technique for obtaining specimens with excellent imaging power. The convex type of echoendoscope used with EUS FNAB provides images perpendicular to the endoscope, which differ from those of popular radial echoendoscopes and, hence, require different usage techniques. Color flow imaging is used to avoid the vessels in and around the mass during puncturing. EUS FNAB for submucosal tumors is sometimes difficult because the needle slips easily, and the gastrointestinal wall tends to be stretched when pushing the needle, which can be solved by making a dimple on the wall before puncturing. Lesions of the pancreas head, especially those at the uncus, and lymph nodes near the superior mesenteric artery are also difficult because of their distance from the endoscope and the resultant bending of the needle. Tissue sampling is more successful when the angle between the endoscope and the needle is kept at just less than 45 degrees, as this helps to transmit the hand force to the needle effectively. The complication rate of EUS FNAB is reportedly 1–2%, and so the technique is considered a safe modality, except for cystic lesions of the pancreas. Recent histological evidence is needed before applying medical therapies, such as chemoradiation and surgery, especially when imaging modalities alone cannot supply the evidence of malignancy; hence increasing importance of EUS FNAB is expected.

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.

We investigated the rates of the treatments and their prognoses in 450 patients with hepatocellular carcinoma (HCC), in order to determine the usefulness of percutaneous microwave coagulation therapy (PMCT) given the present situation of treatment for HCC. Rates of initial treatments were hepatectomy in 31%, percutaneous ethanol injection therapy (PEIT) in 19%, transarterial embolization (TAE) and PEIT in 16%, TAE in 14%, hepatic arterial chemotherapy (HAC) in 7%, PMCT in 7% and others in 6% of cases. The prognosis of PMCT in patients with a single tumor 3 cm in size or less was comparable to that with hepatectomy. Recurrence was found in about 59% of 387 patients who underwent radical treatment initially, and about 96% of these were intrahepatic recurrences. Rates of treatment for intrahepatic recurrence were TAE in 59%, PEIT in 33%, HAC in 31%, PMCT in 24% and hepatectomy in 4% of cases. Indications for use of PMCT were more restricted than for PEIT for reasons of safety. Therefore, the rate of use of PMCT as initial treatment was lower than that of PEIT. On the other hand, the rate of use of PMCT in treatment of recurrence was similar to that of PEIT. PMCT should be used not only as initial treatment but also in the treatment of recurrence, in which HCC is often found at a size 3 cm or less, considering the high incidence of intrahepatic recurrence of HCC as well as reliability of the therapeutic effect and low invasiveness attached to PMCT.

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.

was not preventing the activated T cells from proliferating as the numbers were not reduced in the ASM981relative to vehicle-treated mice Conclusions:ASM981 is highly effective in a dlerapeutic setting. ASM981 has strong effects on some of the downstream systemic inthmmatory reactions in this model. The data from th~s severe chronic model of IBD together with the already impressive findings in chronic inflammatory skin disorders lead as to expect ASM981 to be effective in IBD in man