Staple-Line Reinforcement of the Duodenal Stump With Intracorporeal Lembert's Sutures in Laparoscopic Distal Gastrectomy With Roux-en-Y Reconstruction for Gastric Cancer.

PURPOSE: We report a duodenal stump reinforcement procedure in laparoscopic distal gastrectomy with Roux-en-Y reconstruction. METHODS: We retrospectively reviewed the data of 223 patients who underwent laparoscopic distal gastrectomy with Roux-en-Y reconstruction for gastric cancer. We compared 2 groups: group NR (not reinforced, n=102, June 2009 to December 2011) when we did not perform reinforcement of the duodenal stump, and group R (reinforced, n=121, January 2012 to July 2014) when we did the reinforcement. The duodenum was divided with an endoscopic linear stapler. In group R, the duodenal staple line was reinforced by hand-sewn Lembert's sutures. RESULTS: There were no significant differences between group NR and R in patients' characteristics. Duodenal stump leakage occurred in 2 patients in group NR (2.0%). By contrast, in R group, no patients had duodenal stump leakage or fistula. CONCLUSIONS: Duodenal stump leakage can be avoided by using reinforcement with Lembert's sutures.

Antitumor effect of angiotensin II type 1 receptor blocker losartan for orthotopic rat pancreatic adenocarcinoma.

OBJECTIVE: The aim of this study was to investigate the synergistic inhibitory effects of gemcitabine and losartan, angiotensin II type 1 (AT1) receptor blockers, on an orthotopic rat pancreatic cancer model. METHODS: The rat orthotopic pancreatic cancer model was prepared using DSL-6A/C cells, a rat ductal pancreatic adenocarcinoma cell line. The rats were treated with gemcitabine alone (100 mg/kg per week), losartan alone (100 mg/kg per day), or gemcitabine plus losartan. RESULTS: Survival was significantly improved by treatment with gemcitabine (89.6 ± 21.8 days) or losartan (76.9 ± 18.7 days) alone compared with that in the control group (59.6 ± 13.4 days; P < 0.05). Treatment with gemcitabine plus losartan further prolonged the survival time to 102.6 ± 16.5 days compared with that in the control group (P < 0.0001). Gemcitabine or losartan significantly and dose-dependently reduced the proliferation of DSL-6A/C cells in vitro. Both drugs inhibited pancreatic vascular endothelial growth factor expression compared with that in the control group (P < 0.05). CONCLUSIONS: The results of this study indicate that combined treatment with gemcitabine and losartan significantly improved the survival of rats with orthotopic pancreatic cancer by inhibiting vascular endothelial growth factor synthesis and suppressing cancer cell proliferation via AT1 receptor blockade. Thus, an AT1 receptor blocker in combination with gemcitabine might improve the clinical outcomes of patients with advanced pancreatic cancer.

Activation of alpha-smooth muscle actin-positive myofibroblast-like cells after chemotherapy with gemcitabine in a rat orthotopic pancreatic cancer model.

BACKGROUND: To investigate the behavior of activated pancreatic stellate cells (PSCs), which express alpha-smooth muscle actin (α-SMA), and pancreatic cancer cells in vivo, we examined the expression of α-SMA-positive myofibroblast-like cells in pancreatic cancer tissue after treatment with gemcitabine (GEM) using a Lewis orthotopic rat pancreatic cancer model. METHODS: The effect of GEM on DSL-6A/C1 cell proliferation was determined by cell counting method. The orthotopic pancreatic cancer animals were prepared with DSL-6A/C cells, and treated with GEM (100 mg/kg/weekly, for 3 weeks). At the end of treatment, α-SMA expression, fibrosis, transforming growth factor (TGF)-ß1 and vascular endothelial growth factor (VEGF) were evaluated by histopathological and Western blot analyses. RESULTS: DSL-6A/C1 cell proliferation was significantly reduced by co-culturing with GEM in vitro. Survival time of pancreatic cancer animals (59.6 ± 13.4 days) was significantly improved by treatment with GEM (89.6 ± 21.8 days; p = 0.0005). Alpha-SMA expression in pancreatic cancer tissue was significantly reduced after treatment with GEM (p = 0.03), however, there was no significant difference in Sirius-red expression. Expression of VEGF was significantly reduced by GEM treatment, but the expression of TGF-ß1 was not inhibited. CONCLUSION: GEM may suppress not only the tumor cell proliferation but also suppress PSCs activation through VEGF reduction.

Circulating myeloid dendritic cells as prognostic factors in patients with pancreatic cancer who have undergone surgical resection.

OBJECTIVE: Pancreatic cancer is a malignant neoplasm with poor prognosis that might be associated with defective immune function. We aimed to determine the influence on survival of circulating myeloid dendritic cells (c-m-DCs), circulating lymphoid DCs (c-l-DCs), and DCs within the tumor tissue in patients with pancreatic cancer. PATIENTS AND METHODS: Between December 2001 and June 2006, of a total of 110 patients with ductal adenocarcinoma of the pancreas, 42 underwent pancreatectomy, and 68 had unresectable disease. Numbers of c-m-DCs and c-l-DCs were assessed by flow cytometry, and DCs in the tumor tissue by immunohistochemical staining with anti-fascin mAb. RESULTS: The percentage of the c-m-DCs subset in pancreatic cancer patients was significantly lower than in healthy volunteers, and the similar finding was observed between patients who underwent surgical resection and non-resection. Patients with a high percentage of c-m-DCs or with many DCs accumulated in the cancer tissue survived longer than patients with a low percentage or low number in peripheral blood or the tumor, respectively. Moreover, there was a positive correlation between c-m-DCs within peripheral blood mononuclear cells and the number of DCs per field in the cancer tissue. CONCLUSIONS: Preoperative c-m-DCs levels in the PBMC of patients with pancreatic cancer and DCs counts in the cancer tissue can be a prognostic factor after surgical resection. Modulating the distribution of DCs may be an effective therapy in pancreatic cancer patients with a dismal prognosis.

Circulating CD4+CD25+ regulatory T cells in patients with pancreatic cancer.

OBJECTIVES: Regulatory T cells (Treg) can inhibit immune responses mediated by T cells. The aim of this study was to evaluate the prevalence of Treg in peripheral blood mononuclear cells from patients with pancreatic cancers in relation to their clinical outcomes. METHODS: Among a total of 100 patients with ductal adenocarcinoma of the pancreas, 40 underwent pancreatectomy and 60 had unresectable disease. Their peripheral blood mononuclear cells were evaluated to determine the proportion of CD4CD25 (FoxP3) T cells, as a percentage of the total CD4 cells, by flow cytometric analysis. RESULTS: The percentage of Treg in the patients with pancreatic cancer was significantly lower than that in the healthy volunteers (P = 0.048), and the patients who underwent surgical resection had lower Treg levels than those with unresectable disease (P = 0.040). Patients in the resected group with a higher percentage of Treg survived longer (P = 0.021). Treg in patients who remained disease free at postoperative 12 months significantly decreased compared to that of the postoperative period (P = 0.009). CONCLUSION: A relative increase in Treg may be related to immunosuppression and tumor progression in patients with pancreatic cancer. The immunological monitoring of Treg may be useful to predict the prognosis for patients with pancreatic cancer.

Feasibility and accuracy of second-look laparoscopy after gastrectomy for gastric cancer.

BACKGROUND: A better method for detecting early peritoneal progression is needed. This study evaluated the feasibility and accuracy of second-look laparoscopy for patients with gastric cancer treated using systemic chemotherapy after gastrectomy. METHODS: Second-look laparoscopy was conducted for patients who had no clinical evidence of distant metastases but had peritoneal metastases or positive peritoneal cytology results without visible metastatic disease at initial surgery, patients who underwent systemic chemotherapy over a 6-month period after surgery, and patients who had no clinical evidence of disease based on imaging study after completion of primary chemotherapy. RESULTS: Between November 2004 and April 2008, 21 patients underwent second-look laparoscopy. At the initial surgery, 13 of these patients underwent total gastrectomy and 8 patients underwent distal gastrectomy. One or two sheets of adhesion barrier were received by 18 patients. The median interval between initial surgery and second-look laparoscopy was 9.8 months (range, 6.6-17.5 months). All second-look procedures were completed laparoscopically, and no patients required conversion to laparotomy. None of the 21 patients experienced postlaparoscopy complications. Whereas 12 patients showed no pathologic evidence of disease, 9 patients showed disease at second-look laparoscopy. There was a significant difference in median survival between the groups with negative and positive results (p = 0.017). The median survival for the negative group has not been determined. All the patients in the positive group received further chemotherapy while showing a good performance status (PS). Six patients were PS 0, and 3 patients were PS 1. The median survival time for this group was 10.1 months. CONCLUSIONS: Second-look laparoscopy was a safe and promising approach to reassessment of peritoneal disease for patients with gastric cancer. The incidence of complications was low, particularly in this group of patients, all of whom had undergone prior gastrectomy.

A new guideline to reduce postoperative morbidity after pancreaticoduodenectomy.

OBJECTIVES: Pancreaticoduodenectomy (PD) is still associated with high morbidity. To reduce the frequency of postoperative complications, we have made revisions in perioperative managements of pancreaticoduodenectomy. METHODS: Subjects were 128 consecutive patients who underwent PD between January 2000 and August 2006. In June 2004, the following new departmental guidelines were introduced: (1) modified Kakita method of pancreaticojejunostomy, (2) omental wrapping, (3) early removal of closed-suction drain, and (4) restrictive use of pancreatic and biliary duct stenting. Operative mortality and morbidity between 77 patients managed conventionally (group A) and 51 patients since 2004 (group B) were compared. Risk factors for postoperative complications were determined. RESULTS: Postoperative morbidity in group B (39%) was significantly lower than in group A (64%; P = 0.019). Occurrence of grade B/C pancreatic fistula (PF) in group B (6%) was significantly lower than in group A (19%; P = 0.0376). Delayed gastric emptying was significantly reduced in group B relative to group A (23% vs 6%; P = 0.0133). Logistic regression analyses showed that the modified Kakita method was a negative independent factor for overall complications, PF, and delayed gastric emptying. CONCLUSIONS: The incidence of overall postoperative complications, grade B/C PF, and delayed gastric emptying after PD has been reduced because of the introduction of a new guideline.