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ABSTRACT: 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)-β1 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-β1 was not inhibited. CONCLUSION: GEM may suppress not only the tumor cell proliferation but also suppress PSCs activation through VEGF reduction.
Journal of hepato-biliary-pancreatic sciences. 11/2012;
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ABSTRACT: BACKGROUND/PURPOSE: In June 2004, a critical pathway for patients undergoing pancreaticoduodenectomy (PD) was introduced. The objective of this study was to determine the clinical value of critical pathway implementation. METHODS: 256 consecutive patients who underwent PD between 2000 and 2010 were divided into 4 groups by date of operation as follows; group A (n = 77), the pre-pathway group; group B (n = 51), the CP implementation group who were managed according to departmental guidelines; group C (n = 78), the group who had no stenting in the reconstruction of PD; and group D (n = 50), the group who had reinforcement of the pancreaticojejunostomy. The success rates of clinical outcomes and post-operative morbidity were compared between each group, year by year and every 50 patients. RESULTS: The success rates of clinical outcomes, including the timings of nasogastric tube removal, discontinuation of prophylactic anti-microbial agent, drain removal, starting oral intake, and patient discharge, were significantly improved in group B relative to group A, and in group C relative to group B. There were no significant differences in mortality and morbidity between any of the groups. All clinical outcomes reached a plateau at 2-3 years or 100-150 patients' operations after critical pathway implementation. CONCLUSIONS: Long-term use of a critical pathway is associated with improved clinical outcomes. A certain period of time or volume of patients is needed for this improvement in clinical outcomes to reach a plateau, which indicates achieving standardization of peri-operative management.
Journal of hepato-biliary-pancreatic sciences. 03/2012;
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Sohei Satoi,
Hiroaki Yanagimoto,
Hideyoshi Toyokawa,
Tomohisa Yamamoto,
Satoshi Hirooka,
Rintaro Yui, So Yamaki,
Yoichi Matsui,
Hiroaki Kitade,
Noboru Tanigawa,
Soichiro Takai,
A-Hon Kwon
Pancreas 03/2012; 41(2):333-5. · 2.39 Impact Factor
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ABSTRACT: 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.
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.
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).
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.
Pancreas 12/2011; 41(3):409-15. · 2.39 Impact Factor
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ABSTRACT: Pancreatic cancer is a malignant neoplasm with a poor prognosis that might be associated with defective immune function. In this study, we aimed to clarify the role of circulating myeloid dendritic cells (cmDCs) and lymphoid (cl) DCs in patients with unresectable pancreatic cancer.
This study covered the period from January 2001 to December 2009, and involved 104 patients with unresectable pancreatic cancer. We measured the number of cmDCs and clDCs using flow cytometry before and after chemotherapy, chemoradiotherapy and immuno-chemotherapy.
The percentage of the cmDC subset in the unresectable pancreatic cancer patients was significantly lower than in healthy volunteers (p=0.006). There was no difference in the cmDC subset between patients with distant organ metastasis and locally advanced pancreatic cancer. The patients with a high percentage (≥0.23%) of cmDC subset survived longer than patients with a low percentage (<0.23%) (p=0.0030). Multivariate analysis showed that cmDC was the only independent prognostic factor (p=0.0059). The percentage of cmDC subset was significantly increased after immuno-chemotherapy (p=0.0055).
A high level of cmDCs is associated with better survival rate and is an independently favorable prognostic factor in patients with unresectable pancreatic cancer. It is likely that immunochemotherapy increases the number of cmDCs.
Anticancer research 11/2011; 31(11):3827-34. · 1.73 Impact Factor
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Sohei Satoi,
Hiroaki Yanagimoto,
Hideyoshi Toyokawa,
Kentaro Inoue,
Keita Wada,
Tomohisa Yamamoto,
Satoshi Hirooka, So Yamaki,
Rintaro Yui,
Hynek Mergental,
A-Hon Kwon
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ABSTRACT: 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.
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.
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.
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.
Pancreas 12/2010; 40(3):426-32. · 2.39 Impact Factor
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ABSTRACT: We explored the outcome of the multi-disciplinary management for obtaining long-term survivors in patients with pancreatic cancer that extended beyond the pancreas. This single-institution experience indicates that surgical resection following the neoadjuvant chemoradiation (NACRT) therapy is able to increase the resectability rate with clear margins and to decrease the rate of metastatic lymph nodes, resulting in improved prognosis of curative cases with pancreatic cancer that extended beyond the pancreas.
Gan to kagaku ryoho. Cancer & chemotherapy 11/2010; 37(12):2271-3.
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ABSTRACT: 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).
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).
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.
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.
Pancreas 10/2010; 40(1):16-20. · 2.39 Impact Factor
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Sohei Satoi,
Hideyoshi Toyokawa,
Hiroaki Yanagimoto,
Tomohisa Yamamoto,
Satoshi Hirooka,
Rintaro Yui, So Yamaki,
Kanji Takahashi,
Yoichi Matsui,
Hynek Mergental,
A-Hon Kwon
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ABSTRACT: After standardization of the perioperative management of pancreaticoduodenectomy, we retrospectively compared results in nonstented pancreaticojejunostomy with external-stented pancreaticojejunostomy.
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.
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.
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.
Pancreas 11/2009; 39(2):165-70. · 2.39 Impact Factor
