So Yamaki

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 CD4+CD25+ (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.

Selective use of staging laparoscopy based on carbohydrate antigen 19-9 level and tumor size in patients with radiographically defined potentially or borderline resectable pancreatic cancer.

Objective: The aims of this study were to verify whether the selective use of staging laparoscopy can prevent unnecessary laparotomy and to find a surrogate marker for surgical unresectability in patients with potentially or borderline resectable pancreatic cancer. Methods: Group A consisted of consecutive 33 patients evaluated between 2005 and 2006 and who directly underwent open laparotomy for planned surgical resection. Group B consisted of consecutive 61 patients evaluated between 2007 and 2009 and of whom 16 patients (26%) had a staging laparoscopy due to the presence of high-risk markers of unresectability defined as carbohydrate antigen 19-9 level 150 U/mL or greater and tumor size 30 mm or greater. Results: The frequency of unnecessary laparotomies for occult distant organ metastasis was significantly different between groups A and B (18% and 3%, respectively; P = 0.021). Of 16 patients who underwent staging laparoscopy in group B, 5 patients (31%) had occult metastases. The multivariate analysis showed that the presence of high-risk markers and extrapancreatic plexus invasion on multidetector-row computed tomography were significant independent risk factors for unresectability. Conclusions: The presence of high-risk markers was associated with surgical unresectability in patients with potentially or borderline resectable pancreatic cancer. The selective use of staging laparoscopy decreased the frequency of unnecessary laparotomy by detecting minute metastases.

Is a nonstented duct-to-mucosa anastomosis using the modified Kakita method a safe procedure?

Objectives: After standardization of the perioperative management of pancreaticoduodenectomy, we retrospectively compared results in nonstented pancreaticojejunostomy with external-stented pancreaticojejunostomy. Methods: The study population included 129 consecutive patients who underwent pancreaticoduodenectomy between 2004 and 2008. The postoperative mortality and morbidity were compared between 51 patients with restrictive use of external stenting (group A) and 78 patients without external stenting (group B). The patient with a pancreatic duct of less than 3 mm in diameter was 31% in group A and 46% in group B. Results: There were no differences in postoperative morbidity and mortality between the 2 groups. Although the frequency of overall postoperative pancreatic fistula development was significantly higher in group B than in group A (44% vs 27%, P = 0.0004), there was no difference in grade B/C postoperative pancreatic fistula rate (group A: 5.9% vs group B: 14.1%). The length of in-hospital stay in group B was significantly shorter than group A (13 vs 24 days, P < 0.0001). There were no differences in postoperative morbidity and mortality between subgroups that were consisted of patients with small pancreatic duct diameter. Conclusion: This retrospective single-center study showed that nonstented duct-to-mucosa anastomosis was a safe procedure and was associated with a shortened in-hospital stay.

Effects of pancrelipase on nonalcoholic fatty liver disease after pancreaticoduodenectomy

Postoperative nonalcoholic fatty liver disease (NAFLD) after pancreaticoduodenectomy (PD) has recently become recognized. However, the pathoetiology of postoperative NAFLD is largely unknown. Furthermore, the optimal treatment has not been established. The aim of this prospective study was to clarify whether pancrelipase, which contains digestive pancreatic enzymes, could reverse NAFLD.

Reinforcement of pancreticojejunostomy using polyglycolic acid mesh and fibrin glue sealant.

Objectives: To examine whether pressure-tight reinforcement of pancreaticojejunostomy (PJ) using polyglycolic acid (PGA) mesh and fibrin glue sealant can reduce the incidence of postoperative pancreatic fistula (POPF). Methods: The study population included 128 consecutive patients who underwent pancreaticoduodenectomy between September 2006 and January 2010. Postoperative mortality and morbidity among 50 patients who underwent reinforcement of PJ anastomosis using PGA mesh and fibrin glue were compared with 78 patients (historical controls). Results: The 2 groups demonstrated no significant differences in frequencies of overall or septic complications, reoperation, or in-hospital death. No significant difference in the frequency of POPF, delayed gastric emptying, or intra-abdominal abscess was found between groups. There was no difference between the 2 groups in the number of necessary interventions, and no bleeding complications or POPF-related mortality occurred. The median length of postoperative in-hospital stay between the 2 groups was similar: 13 days (range, 8-101 days) versus 14 days (range, 8-61 days). Similar findings were observed in a subgroup analysis consisting of patients with a pancreatic duct diameter smaller than 3 mm. Conclusion: This retrospective single-center study showed that reinforcement of PJ anastomosis using PGA mesh and fibrin glue provided no significant benefit in reducing the frequency of POPF.

Pancreaticogastrostomy following distal pancreatectomy prevents pancreatic fistula‐related complications

The most common postoperative complication after distal pancreatectomy (DP) is still postoperative pancreatic fistula (POPF), which is closely associated with other major complications and remains an unsolved problem.

Less morbidity after introduction of a new departmental policy for patients who undergo open distal pancreatectomy

The aim of this study was to retrospectively compare morbidity and mortality before and after introduction of a new departmental policy for patients who undergo distal pancreatectomy.

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.

Potential role of surgical resection for pancreatic cancer in the very elderly

BACKGROUND There is increasing need to evaluate the surgical indication of pancreatic cancer in very elderly patients. However, the available clinical data are limited, and the optimal treatment is still controversial. The aim of this study was to evaluate the benefit of pancreatic resection in pancreatic cancer patients over the age of 80. METHODS Between 2005 and 2012, 26 octogenarian patients who received pancreatic resection and 20 who received chemotherapy for pancreatic cancer were retrospectively reviewed. Clinicopathological factors, chemotherapy administration status, and survival were compared. Univariate and multivariate analysis of prognostic factors for survival was performed. RESULTS Postoperative major complication rate was 8%, with no mortality. The one-year survival rate and median survival time of the surgery and chemotherapy groups were 50% and 45%, and 12.4 months and 11.7 months, respectively (P = 0.263). Of the 26 resected cases, 6 completed the planned adjuvant chemotherapy treatment course. The median survival time of those 6 completed cases was significantly longer than that of the 20 not completed cases (23.4 versus 10.0 months, P = 0.034). Furthermore, a multivariate analysis of the 26 resected cases showed that distant metastasis (HR 3.206, 95%CI 1.005-10.22, P = 0.049) and completion of the planned adjuvant therapy (HR 4.078, 95%CI 1.162-14.30, P = 0.028) were independent prognostic factors of surgical resection. CONCLUSIONS Surgical resection was safe, but not superior to chemotherapy for pancreatic cancer in octogenarians. In the very elderly, only selected patients may benefit from pancreatic resection.

Role of adjuvant surgery in initially unresectable pancreatic cancer after long-term chemotherapy or chemoradiation therapy: survival benefit?

The purpose of the present study was to analyze the survival benefit and safety of adjuvant surgery in patients with initially unresectable pancreatic cancer following chemo(radio)therapy.