Soichiro Takai

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)

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.

Intrahepatic sarcomatoid cholangiocarcinoma.

A 69-year-old woman was admitted to our hospital with fever and abdominal pain in the epigastric region. Abdominal ultrasonography demonstrated a well-defined hypoechoic mass in the epigastric region with encasement of the left hepatic lobe and stomach. Computed tomography confirmed a low-density mass, 20 cm in diameter, with enhancing peripheral areas. Angiography revealed the tumor to be hypovascular. After admission, the patient had a persistent fever and anemia that required transfusions of concentrated red blood cells. On the twelfth day after admission, she suffered disseminated intravascular coagulation and underwent an emergency operation. A lateral segmentectomy with dissection of lymph nodes, cholecystectomy, and hemigastrectomy were carried out. The size of the tumor was 22 × 17 × 15 cm. Macroscopically, a cross-section revealed massive necrosis with hemorrhage. Histological examination of the tumor showed a malignant neoplasm with a carcinomatous component and a sarcomatous component, which were partly intermingled. The former consisted of moderately differentiated adenocarcinoma, while the latter consisted of pleomorphic spindle cells. Immunohistochemical examination of the sarcomatous component showed positive staining for vimentin, epithelial membrane antigen, and cytokeratin. The tumor was diagnosed as cholangiocarcinoma with extensive sarcomatous changes, based on these histological and immunohistochemical findings. The patient had an uneventful postoperative course. However, she died 3 months after surgery from dissemination of the carcinoma. The literature on this rare disease is reviewed and discussed.

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.

Less morbidity after pancreaticoduodenectomy of patients with pancreatic cancer.

Objectives: The pancreaticoduodenectomy with extended resection has been frequently performed in patients with pancreatic cancer in Japan. One result of this additional surgical stress may be that postoperative complications in patients with pancreatic cancer are more frequent than in patients with periampullary cancer. Methods: The 198 patients with pancreatic and periampullary cancer underwent pancreaticoduodenectomy. The operative mortality and morbidity between patients with pancreatic and periampullary cancer were compared, and the risk factors of postoperative complications and in-hospital death were determined. Results: Patients with pancreatic and periampullary cancer made up 52% and 48% of total patients. The duration of surgery and volume of intraoperative blood loss were significantly higher in patients with pancreatic cancer than in patients with periampullary cancer. Additional organ resections were frequently performed in patients with pancreatic cancer. However, significantly lower morbidity rates were observed in patients with pancreatic cancer. Among all complications evaluated, pancreatic fistula and abdominal abscess were found less frequently in patients with pancreatic cancer. Logistic regression analyses showed a positive correlation between periampullary cancer and an increased risk of complications, pancreatic fistula, and abdominal abscess. The in-hospital mortality rate has significantly reduced since 2000. When pancreatic fistula was clinically diagnosed, we immediately started a closed lavage using continuous administration of natural saline at 1000 to 4000 mL/d, after exchange of a nasogastric tube drain. Conclusion: Pancreaticoduodenectomy for patients with pancreatic cancer can be a safe procedure in spite of surgical stress. Further surgical strategies will be needed to reduce postoperative complications, especially in patients with periampullary cancer.

Laparoscopic Splenectomy for a Lymphangioma of the Spleen: Report of a Case

Abstract We present the first case report of a suc-cessful laparoscopic complete excision of a splenic lymphangioma. The splenic tumor was preoperatively diagnosed to be a lymphangioma by the combined modalities of ultrasonography, computed tomography, magnetic resonance imaging, and angiography. A laparoscopic splenectomy was subsequently performed and the pathological examination of the mass confirmed the diagnosis of a lymphangioma. Based on the above findings, a laparoscopic splenectomy is recommended when a splenic tumor is suspected to be either benign or borderline.