Cytokines and growth factors in malignant ascites are thought to modulate a variety of cellular activities of cancer cells and normal host cells. The motility of cancer cells is an especially important activity for invasion and metastasis. Here, we examined the components in ascites, which are responsible for cell motility, from patients and cancer cell-injected mice. Ascites remarkably stimulated the migration of pancreatic cancer cells. This response was inhibited or abolished by pertussis toxin, monoglyceride lipase, an enzyme hydrolyzing lysophosphatidic acid (LPA), and Ki16425 and VPC12249, antagonists for LPA receptors (LPA 1 and LPA 3 ), but not by an LPA 3 -selective antagonist. These agents also inhibited the response to LPA but not to the epidermal growth factor. In malignant ascites, LPA is present at a high level, which can explain the migration activity, and the fractionation study of ascites by lipid extraction and subsequent thin-layer chromatography indicated LPA as an active component. A significant level of LPA 1 receptor mRNA is expressed in pancreatic cancer cells with high migration activity to ascites but not in cells with low migration activity. Small interfering RNA against LPA 1 receptors specifically inhibited the receptor mRNA expression and abolished the migration response to ascites. These results suggest that LPA is a critical component of ascites for the motility of pancreatic cancer cells and LPA 1 receptors may mediate this activity. LPA receptor antagonists including Ki16425 are potential therapeutic drugs against the migration and invasion of cancer cells.

Pancreatic fistula is a major form of morbidity following pancreatic resection. We conducted a nonrandomized clinical trial comparing the sealing and sandwich techniques of spraying fibrin glue to prevent pancreatic fistula following distal pancreatectomy. The pancreas was transected with a scalpel to identify and suture the main pancreatic duct and its small branches. In the sealing group, fibrin glue was sprayed over the closed pancreatic stump and sutures. Alternatively, in the sandwich group fibrin glue was sprayed so as to cover and join the cut surface of the pancreatic remnant, which was then held closed with sutures. Altogether 111 patients were included in the study (90 with gastric cancer, 10 with esophageal cancer, and 11 with pancreatic cancer). Patients were nonrandomly assigned to the sandwich or the sealing group. Morbidity was 21.8% for the patients in the sandwich group versus 33.9% in the sealing group. Pancreatic fistulas occurred in 9.0% of the sandwich group versus 26.8% of the sealing group. The incidence of fistula was thus significantly lower in the sandwich group. The incidence of fistula was also significantly lower in the sandwich group for gastric malignancy patients undergoing extended radical lymphadenectomy down to the paraaortic lymph nodes combined with left adrenalectomy. Of the patients with gastric malignancy, pancreatic fistulas occurred in 9.3% of the sandwich group versus 25.5% of the sealing group. The fibrin glue sandwich technique is simple and reliable and should be valuable for complementing other prophylactic methods of preventing pancreatic fistula.

Background: Pancreatic fistula is a leading cause of morbidity and mortality after pancreaticoduodenectomy, and an external stent of pancreaticojejunostomy has been recommended to prevent pancreatic fistula. Hypothesis: Duct-to-mucosa pancreaticojejunostomy should not require placement of an external stent.

Patients with ACC involving both the liver and IVC are candidates for partial hepatectomy and segmental IVC resection. Resection affords the possibility of negative margins, acceptable perioperative morbidity and mortality, and prolonged survival in some patients.

Protein-bound polysaccharide K (PSK) increased the 5-year disease-free survival rate and reduced the risk of recurrence in a randomised, controlled study for stage II and III colorectal cancer. In order to elucidate the disease-free survival benefits with PSK and what immunological markers could indicate a PSK responder, serial changes in immunological parameters were monitored in the study. PSK decreased the mean serum immunosuppressive acidic protein (IAP) level, and increased the mean population of natural killer (NK) cells compared with the controls. The 5-year disease-free and overall survival rate for patients with serum IAP values ≤500 μg ml -1 , which represents the normal value, were 75.5% (95% CI: 66.8-84.2%; p=0.016) and 85.1% (95% CI: 77.9-92.3%; p=0.032), respectively, in the PSK group compared with 57.5% (95% CI: 43.3-71.6%) and 70.2% (95% CI: 57.1-83.3%) in the control group. In patients with NK cell population ≥8% at 3 months after surgery, PSK conferred a significantly better (p=0.038) 5-year disease-free survival (86.7%; 95% CI: 74.5-98.8%) compared to the control group (60.0%; 95% CI: 29.6-90.4%).In the proportional hazards model, the presence of regional metastases (relative risk, 3.595; 95% CI: 1.518 to 8.518; p=0.004) and omission of PSK treatment (relative risk, 3.099; 95% CI: 1.202 to 7.990; p=0.019) were significant indicators of recurrence. PSK acts as an immunomodulatory activity and biochemical modulator in stage II or III colorectal cancer. Pre-operative serum IAP values ≤500 μg ml -1 and an NK cell population ≥8% at 3 months after surgery are possible PSK response predictors.