Lysophosphatidic acid enhances human hepatocellular carcinoma cell migration, invasion and adhesion through P38 MAPK pathway.

BACKGROUND/AIMS: Lysophosphatidic acid (LPA) has diverse biological activities implicated in tumor progression, including increasing cell migration, invasion and metastasis. However, the underlying mechanisms for LPA-induced human hepatocellular carcinoma (HCC) migration and invasion are poorly understood. METHODOLOGY: We sought to determine the promoting effect of LPA on HCC migration, invasion and adhesion by transwell and matrix adhesion assays, respectively. Levels of matrix metalloproteinase, MMP-2 and MMP- 9 from cells were assayed by ELISA and p38 mitogenactivated protein kinase (MAPK) signaling was determined by western blot analysis. RESULTS: In the present study, LPA was found to increase HCC cell migration, invasion and adhesion. In addition, LPA increased MMP-9 expression level and induced activation of the p38 mitogen- activated protein kinase (MAPK) signaling. Furthermore, pharmacological inhibition of p38 MAPK signal pathway with SB203580 significantly attenuated LPA-induced HCC cell migration, invasion, and adhesion and abrogated LPA-induced MMP-9 expression and p38 MAPK phosphorylation. CONCLUSIONS: We demonstrated a mechanism that LPA can activate p38 MAPK signaling, which is required for LPA-induced HCC cell migration, invasion, adhesion and MMP-9 expression, providing a novel biomarker and potential therapeutic target for HCC.

Combined invagination and duct-to-mucosa techniques with modifications: a new method of pancreaticojejunal anastomosis.

BACKGROUND: Soft pancreatic texture and a small main pancreatic duct are thought to be the most significant risk factors for the occurrence of pancreatic fistula (PF), a common and serious complication after pancreaticoduodenectomy (PD). This is in part due to the technical difficulties of pancreaticojejunostomy (PJ) posed by a soft gland with a normal-sized duct. To deal with this problem, we developed a new anastomotic technique which combines the two most widely used techniques, namely, the invagination technique and the duct-to-mucosa technique, with a modification of the suture route and insertion of a temporary stent tube. METHODS: Between January 2003 and December 2009, ninety-two consecutive patients underwent PD in which the new PJ technique was used. Charts and follow-up data of these patients were reviewed for operative details, early postoperative events, and outcomes at 6 months after the operation. PF was defined by the International Study Group on Pancreatic Fistula (ISGPF) guidelines and graded (A, B or C) according to the clinical procedures and outcome. RESULTS: In this group of 92 patients, there was only 1 early death from acute renal failure. PF was observed in 11 patients (12.0%), 8 in grade A, 1 in grade B, and 2 in grade C. For the 2 patients in grade C, PF was surgically managed. There were no early or late deaths attributable to PF. Six months after the operation, all of the patients were free of PJ-related symptoms except for 2, who were found to have steatorrhea. CONCLUSIONS: Our modified technique is simple and safe in PD. Present data suggest that this technique produces excellent early and medium-term results.

Modified Sugiura procedure for the management of 160 cirrhotic patients with portal hypertension.

BACKGROUND: Portal hypertension is a common disease with a high mortality and serious effect on the life quality of patients. Presently, shunt and disconnection are commonly used for surgical treatment of portal hypertension. The aim of this study was conducted to analyze the results of a modified Sugiura procedure for the management of 160 cirrhotic patients with portal hypertension. METHODS: The results of a modified Sugiura procedure for the treatment of 160 cirrhotic patients with portal hypertension from January 1991 to July 2002 were retrospectively analyzed. RESULTS: The operative mortality for the procedure was zero. Postoperative intra-abdominal bleeding was noted in 2 patients, drowned lung in 1, pneumonia in 1, and splenic venous thrombosis in 4. Of the 160 patients, 157 (98%) were followed up from 6 months to 11.5 years. Of the 157 patients, only one died of hepatic coma 6 years after operation, and 3 of rebleeding. The absolute and relative survival rates were 97.5%(156/160) and 99%(159/160), respectively. The absolute and relative occurrence rates of hepatic coma were 2.5%(4/160) and 0.6%(1/157), respectively. The absolute and relative occurrence rates of rebleeding were 3.8%(6/160) and 1.9%(3/157), respectively. In 96 of 116 Child B patients (82.8%), liver function improved from preoperative class B to A 3 months after operation. Sixty-five patients were subjected to gastroscopy and 22 patients, esophageal barium photography 6 months after operation. Gastro-esophageal varices disappeared in 56 patients (64.4%, 56/87), obviously improved in 30 (34.5%, 30/87), and unchanged in 1 (1.2%, 1/87). The occurrence rate of portal hypertensive gastropathy (PHG) was 13.9%(9/65). CONCLUSION: Our results showed that the modified Sugiura procedure is effective in the treatment of portal hypertension, with a low rate of operative complication, bleeding recurrence, and hepatic coma.

Pancreaticoduodenectomy with Roux-Y anastomosis in reconstructing the digestive tract: report of 26 patients.

OBJECTIVE: To explore the way to lower the morbidity and mortality of patients after pancreaticoduodenectomy. METHODS: Between March 1998 and March 2001, 26 patients with periampullary tumors received pancreaticoduodenectomy (PD) with Roux-Y anastomosis to reconstruct the digestive tract. Of these patients, 6 had ductal cell carcinoma at the head of the pancreas, 8 distal common bile duct carcinoma, 5 ampullar adenocarcinoma of the Vater, 6 duodenal adenocarcinoma, and 1 duodenal malignant lynphoma. A 30-40 cm free vascularized segment of the proximal jejunum was taken and pulled up to the bed of the duodenum for end-to-end pancreaticojejunostomy, end-to-side choledocojejunostomy or side-to-side jejunojejunostomy by a single loop. RESULTS: The operative mortality was zero. Postoperative intraabdominal hemorrhage occurred in 2 patients, but no leakage during pancreaticojejunostomy or choledocojejunostomy as well as abdominal infection. The patients were discharged from the hospital on the tenth to fourteenth day after operation. Follow-up for 5 to 36 months (mean 21 months) revealed chronic steatorrhea and malnutrition in one patient (3.85%), and good digestive function and normal nutritional status in 25 (96.15%). No bile reflux gastritis, retrograde infection, anastomotic ulcer, and dumping syndrome were observed. CONCLUSION: Our results show that this procedure can effectively reduce the morbidity and mortality of patients after PD.