Sohei Satoi

Clinicopathologic evaluation after resection for ductal adenocarcinoma of the pancreas: A retrospective, single-institution experience

Introduction Between April 1992 and December 2000, 167 patients with pancreatic carcinoma were evaluated and treated in our department. One hundred eight patients (64.7%) with pancreatic carcinoma underwent pancreatectomy. Of these patients, 94 had histologically proven ductal adenocarcinoma. The overall postoperative mortality rate was 3.2% (3 patients), and the morbidity rate was 35.1% (33 patients). The estimated 1-, 2-, 3-, and 5-year survival rates were 43.6%, 28.7%, 21.8%, and 12.9%, respectively. There were only six long-term survivors who survived >5 years after surgery. Methodology and Aims Institutional experience with 94 consecutive patients with ductal adenocarcinoma who underwent pancreatectomy was reviewed to clarify the influence of 29 prognostic factors (5 host, 17 tumor, and 7 treatment factors). Special reference was made to determine whether these significant factors have an effect on long-term survival. Univariate and multivariate models were used to analyze the effect of prognostic factors on survival. Results Univariate analysis indicated that blood loss, operative time, postoperative complications, histopathologic lymphatic and venous permeation, lymph node metastasis, conclusive stage, conclusive curability, resection margins, serosal invasion, size of tumor, retroperitoneal invasion, major arterial invasion, and mode of histologic infiltration were associated with significantly longer survival (p < 0.05). By Cox proportional hazards survival analysis, the most powerful predictors of outcome were venous permeation, lymph node metastasis, tumor diameter, and conclusive curability. The longest-term survivor had the most advanced stage (stage IVb) of disease and curability C. No long-term survivors had all of the good prognostic factors (according to multivariate analysis). Conclusions The prognosis after surgical resection of pancreatic carcinoma mostly depends on tumor factors. In this study, it was difficult to identify the determinants of long-term survival in patients with resectable tumors.

Improved prognosis of postoperative hepatocellular carcinoma patients when treated with functional foods: a prospective cohort study

BACKGROUND/AIMS Active hexose correlated compound (AHCC) is a newly developed functional food. In vitro experiments have shown that AHCC enhances natural killer cell activity, and may be considered a potent biological response modifier in the treatment of cancer patients. However, the effects of AHCC in a clinical setting have not been reported. We seek to determine whether AHCC can improve the prognosis of hepatocellular carcinoma (HCC) patients following surgical treatment. METHODS A prospective cohort study was performed from February 1, 1992 to December 31, 2001. A total of 269 consecutive patients with histologically confirmed HCC were studied. All of the patients underwent resection of a liver tumor. Time to treatment failure (disease recurrence or death) and ten parameters related to liver function after surgery were examined. RESULTS Of the 269 patients, 113 received AHCC orally after undergoing curative surgery (AHCC group). The AHCC group had a significantly longer no recurrence period (hazard ratio (HR), 0.639; 95% confidence interval (CI), 0.429-0.952; P=0.0277) and an increased overall survival rate (HR, 0.421; 95% CI, 0.253-0.701; P=0.0009) when compared to the control group by Coxs multivariate analysis. CONCLUSIONS This study suggests that AHCC intake can improve the prognosis of postoperative HCC patients.

Surgical results after preoperative chemoradiation therapy for patients with pancreatic cancer.

Objectives: The results of surgical therapy alone for pancreatic cancer are disappointing. We explored surgical results after neoadjuvant chemoradiation therapy (NACRT) for patients with pancreatic cancer that extended beyond the pancreas. Methods: Sixty-eight consecutive patients with pancreatic cancer who underwent pancreatic resection were included. Twenty-seven patients underwent surgical resection after NACRT (NACRT group). The other 41 patients were classified as surgery-alone group. Surgical results were compared in patients who underwent curative resection (R0/1) who were followed up for at least 25 months and underwent no adjuvant therapy. Results: A lower frequency of lymph node metastasis was observed in the NACRT group (P < 0.05). The frequency of residual tumor grading in the NACRT group was significantly different from that in surgery-alone (R0/1/2%, 52/15/33 vs 22/51/27; P = 0.0040). In R0/1 cases, overall survival and disease-free survival rates in the NACRT group (n = 18) were significantly longer than in surgery-alone (n = 30, P < 0.05). The rate of local recurrence in the NACRT group was significantly less than in surgery-alone (11% vs 47%, P = 0.0024). Conclusions: This single-institution experience indicates that NACRT 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.

Immunological evaluation of personalized peptide vaccination with gemcitabine for pancreatic cancer

The aim of the present study was to investigate the safety and immune responses of personalized peptide vaccination when administered with gemcitabine (GEM) in advanced pancreatic cancer (APC) patients. Thirteen patients with APC were enrolled. Pre‐vaccination with peripheral blood mononuclear cells and plasma was carried out to examine cellular and humoral responses to 25 or 23 peptides in human leukocyte antigen A24++ or A2+++ patients, respectively. Only the reactive peptides (maximum of four) were then administered weekly at three different dose settings: 1, 2 and 3 mg of peptide. GEM was administered at 1000 mg/m2 per week for 3 weeks, followed by 1 week of rest. The combination therapy was well tolerated. Grade 3 toxicities were: anemia (three patients), neutropenia (two patients) and thrombocytopenia (two patients). Of these 13 patients, 11 (85%) showed clinical responses, such as reduction in tumor size and/or level of tumor markers. Augmentation of peptide‐specific cytotoxic T lymphocyte activity against pancreatic cancer cells was observed at each dose level, whereas the increment of peptide‐specific IgG antibodies was dependent on peptide dose. GEM did not inhibit the immune responses induced by personalized peptide vaccinations, and this new type of immunochemotherapy combination is recommended for further clinical study in APC patients. (Cancer Sci 2007; 98: 605–611)

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.

Involvement of inducible costimulator- and interleukin 10-positive regulatory T cells in the development of IgG4-related autoimmune pancreatitis.

Objectives: Immunoglobulin G4 (IgG4)-related autoimmune pancreatitis (AIP) is a new clinical entity of pancreatic disorder. There are immunologic and histological abnormalities, including increased serum IgG4 levels and the infiltration of IgG4-positive plasmacytes. However, the role of IgG4 is unclear. Recently, regulatory T cells (Tregs) were reported to contribute to the development of various autoimmune diseases as well as in B-cell shifting to IgG4-producing plasmacytes. We studied Tregs in the pancreas and peripheral blood. Methods: We recruited 44 patients with IgG4-related AIP. For comparison, we recruited 37 patients with other pancreatic diseases and 27 healthy subjects as controls. We studied infiltrating cells in the pancreas by immunohistochemistry and analyzed inducible costimulator-positive Tregs and interleukin 10-positive Tregs in the peripheral blood by flow cytometry. Results: The ratio of Foxp3-positive cells to infiltrated mononuclear cells (Foxp3/Mono) in AIP patients was significantly higher than in patients with alcoholic chronic pancreatitis. In AIP, Foxp3/Mono and IgG4/Mono were positively correlated. Inducible costimulator-positive Tregs were significantly higher in AIP patients than in the patients with other pancreatic diseases and the healthy control group. Interleukin 10-positive Tregs were significantly higher in AIP patients than in the healthy control group. Conclusions: Increased quantities of inducible costimulator-positive Tregs may influence IgG4 production in IgG4-related AIP.

Multicenter comparative study of laparoscopic and open distal pancreatectomy using propensity score-matching

Laparoscopic distal pancreatectomy has been shown to be associated with favorable postoperative outcomes using meta‐analysis. However, there have been no randomized controlled studies yet. This study aimed to compare laparoscopic and open distal pancreatectomy using propensity score‐matching.

Neoadjuvant chemoradiation in patients with potentially resectable pancreatic cancer.

Objectives: To retrospectively evaluate the efficacy and tolerability of 5-fluorouracil and low-dose cisplatin (FP)-based preoperative concurrent chemoradiotherapy (PCRT) and gemcitabine (GEM)-based PCRT in patients with potentially resectable pancreatic cancer. Methods: Between December 2000 and December 2004, 32 patients with potentially resectable pancreatic cancer were treated with PCRT. All patients received external beam radiotherapy (total dose of 40 Gy) for 4 weeks. Concurrently, chemotherapy was performed intravenously with continuous 5-fluorouracil 200 mg/m2/d and intermittent cisplatin bolus 3 to 6 mg/m2/d for 4 weeks (Arm FP-PCRT, n = 14) or weekly GEM 400 mg/m2 for 3 weeks (Arm GEM-PCRT, n = 18). The patients were restaged 3 to 4 weeks after the end of PCRT and explored for resection in cases without distant metastases. Results: The 3-year survival rates and median survival were 29.4% and 20.5 months for the resected patients (n = 24) and 0% and 5.5 months for unresected patients (n = 8), respectively (P < 0.0001). The 1-, 2-, 3-year survival rates and median survival were 87.5%, 62.5%, 33.3%, and 26 months for the resected patients treated with FP-PCRT and 75%, 40%, 26.7%, and 19.9 months for the resected patients treated with GEM-PCRT (respectively; P = not significant). Most of the toxicities of both regimens were slight and were in grade1 to 2. Grade 1 to 3 leukopenia (43% vs 100%) and thrombocytopenia (0% vs 39%) were significantly different between the FP-PCRT and GEM-PCRT patients. Conclusions: The PCRT regimens in this article enabled selection of 24 of 32 patients for surgery and resulted in encouraging survival results and acceptable toxicities.

Immunological effect of active hexose correlated compound (AHCC) in healthy volunteers: a double-blind, placebo-controlled trial.

The aim of this study was to evaluate the effects of active hexose correlated compound (AHCC) intake on immune responses by investigating the number and function of circulating dendritic cells (DCs) in healthy volunteers. Twenty-one healthy volunteers were randomized to receive placebo or AHCC at 3.0 g/day for 4 wk. The number of circulating cluster of differentiation (CD)11c+ DCs (DC1) and CD11c− DCs (DC2) were measured. Allogeneic mixed-leukocyte reaction (MLR) was performed. Natural killer (NK) cell activity and the proliferative response of T lymphocytes toward mitogen (phytohemagglutinin [PHA]) were measured. We also measured cytokine production stimulated by lipopolysaccharide [interleukin (IL)-2, IL-4, IL-6, IL-10, interferon gamma-γ, tumor necrosis factor-α). The AHCC group (n = 10) after AHCC intake had a significantly higher number of total DCs compared to that at baseline and values from control subjects (n = 11). The number of DC1s in the AHCC group after intake was significantly higher than at baseline. DC2s in the AHCC group were significantly increased in comparison with controls. The MLR in the AHCC group was significantly increased compared to controls. No significant differences in PHA, NK cell activity, and cytokine production were found between groups. AHCC intake resulted in the increased number of DCs and function of DC1s, which have a role in specific immunity.

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.