Seiya Yoshida

Streptococcal Preparation OK-432 Promotes Fusion Efficiency and Enhances Induction of Antigen-Specific CTL by Fusions of Dendritic Cells and Colorectal Cancer Cells

Dendritic/tumor fusion cell (FC) vaccine is an effective approach for various types of cancer but has not yet been standardized. Antitumor activity can be modulated by different mechanisms such as dendritic cell (DC) maturation state. This study addressed optimal strategies for FC preparations to enhance Ag-specific CTL activity. We have created three types of FC preparations by alternating fusion cell partners: 1) immature DCs fused with autologous colorectal carcinoma cells (Imm-FCs); 2) Imm-FCs followed by stimulation with penicillin-inactivated Streptococcus pyogenes (OK-432) (Imm-FCs/OK); and 3) OK-432-stimulated DCs directly fused to autologous colorectal carcinoma cells (OK-FCs). Both OK-FCs and Imm-FCs/OK coexpressed the CEA, MUC1, and significantly higher levels of CD86, CD83, and IL-12 than those obtained with Imm-FCs. Short-term culture of fusion cell preparations promoted the fusion efficiency. Interestingly, OK-FCs were more efficient in stimulating CD4+ and CD8+ T cells capable of high levels of IFN-γ production and cytolysis of autologous tumor or semiallogeneic targets. Moreover, OK-FCs are more effective inducer of CTL activation compared with Imm-FCs/OK on a per fusion cell basis. The pentameric assay confirmed that CEA- and MUC1-specific CTL was induced simultaneously by OK-FCs at high frequency. Furthermore, the cryopreserved OK-FCs retained stimulatory capacity for inducing antitumor immunity. These results suggest that OK-432 promotes fusion efficiency and induction of Ag-specific CTL by fusion cells. We conclude that DCs fused after stimulation by OK-432 may have the potential applicability to the field of antitumor immunotherapy and may provide a platform for adoptive immunotherapy in the clinical setting.

Transumbilical single-incision laparoscopic hepatectomy using precoagulation and clipless technique in a patient with combined hepatocellular-cholangiocarcinoma: a case report.

We report our first case of single-incision laparoscopic hepatectomy in a 43-year-old woman with a 30-mm solitary combined hepatocellular-cholangiocarcinoma. A port of single-incision laparoscopic surgery was inserted through the abdominal wall using a 2.5-cm single incision in the umbilical area. To obtain adequate operative view for the tumor in segment 6, a 5-mm flexible endoscope, roticulated instruments, and a miniloop retractor were used. After precoagulation with a 5-mm flexible microwave probe, liver resection was performed using laparoscopic ultrasonic shears, soft-coagulation devices, and a tissue-sealing knife. Subsequently, cholecystectomy was carried out for a gallbladder polyp. The procedure was successfully completed without conversion to conventional laparoscopic technique. The operation time was 180 minutes and operative blood loss was uncountable. Transumbilical single-incision laparoscopic hepatectomy using precoagulation and clipless techniques is feasible and seems to provide better cosmetic appearance in selected cases by qualified endoscopic liver surgeons.

Successful adjuvant bi-weekly gemcitabine chemotherapy for pancreatic cancer without impairing patients’ quality of life

BackgroundAlthough adjuvant gemcitabine (GEM) chemotherapy for pancreatic cancer is standard, the quality of life (QOL) in those patients is still impaired by the standard regimen of GEM. Therefore, we studied whether mild dose-intensity adjuvant chemotherapy with bi-weekly GEM administration could provide a survival benefit with acceptable QOL to the patients with pancreatic cancer.MethodsAfter a phase I trial, an adjuvant bi-weekly 1,000 mg/m2 of GEM chemotherapy was performed in 58 patients with pancreatic cancer for at least 12 courses (Group A). In contrast, 36 patients who declined the adjuvant bi-weekly GEM chemotherapy underwent traditional adjuvant 5FU-based chemotherapy (Group B). Careful periodical follow-ups for side effects of GEM and disease recurrence, and assessment of patients’ QOL using the EORTC QOL questionnaire (QLQ-C30) and pancreatic cancer-specific supplemental module (QLQ-PAN26) were performed. Retrospectively, the degree of side effects, patients’ QOL, compliance rate, disease-free survival (DFS), and overall survival (OS) in Group A were compared with those in Group B.ResultsNo severe side effects (higher than Grade 2 according to the common toxicity criteria of ECOG) were observed, except for patients in Group B, who were switched to the standard GEM chemotherapy. Patients’ QOL was better in Group A than B (fatigue: 48.9 ± 32.1 versus 68.1 ± 36.3, nausea and vomiting: 26.8 ± 20.4 versus 53.7 ± 32.6, diarrhea: 21.0 ± 22.6 versus 53.9 ± 38.5, difficulty gaining weight: 49.5 ± 34.4 versus 67.7 ± 40.5, P < 0.05). Compliance rates in Groups A and B were 93% and 47%. There was a significant difference in the median DFS between both groups (Group A : B =12.5 : 6.6 months, P < 0.001). The median OS of Group A was prolonged markedly compared with Group B (20.2 versus 11.9 months, P < 0.005). For OS between both groups, univariate analysis revealed no statistical difference in 69-year-old or under females, and T1–2 factors, moreover, multivariate analysis indicated three factors, such as bi-weekly adjuvant GEM chemotherapy, T2 or less, and R0.ConclusionsAdjuvant chemotherapy with bi-weekly GEM offered not only the advantage of survival benefits but the excellent compliance with acceptable QOL for postoperative pancreatic cancer patients.

Serum Carcinoembryonic Antigen Levels Before the First Curative Hepatectomy for Metastatic Colorectal Cancer Is a Predictor of Recurrence

Background/Aim: The aim of this study was to evaluate the usefulness of serum carcinoembryonic antigen (CEA) levels before the first curative hepatectomy for metastatic colorectal cancer as a predictor of recurrence. Patients and Methods: Between 2003 and 2010, 66 patients (45 male and 21 female) who underwent a first curative hepatectomy for metastatic colorectal cancer in our hospital were evaluated retrospectively. The mean patient age was 65.2 years (range=31-80 years). A total of 28 patients had synchronous liver metastasis, and the other 38 patients developed metachronous liver metastasis. Results: The 5-year relapse-free survival rate after the first hepatectomy of the 16 patients with normal serum CEA level was 61.1%, whereas that of the 50 patients with abnormal serum CEA level was 34.3% (p<0.001). Among patients whose serum CEA levels were abnormal, the 5-year relapse-free survival rate after the first hepatectomy of the 34 patients with serum CEA levels less than 50 ng/ml was 48.1%, whereas that of the 16 patients with serum CEA level equal to or greater than 50 ng/ml was 6.3% (p<0.001). All eleven patients whose serum CEA levels were at least 100 ng/ml developed recurrence within one year after hepatectomy. Conclusion: Serum CEA levels before the first curative hepatectomy for metastatic colorectal cancer seem to be a predictor of recurrence.

Impact of delayed gastric emptying after pancreaticoduodenectomy on survival

Delayed gastric emptying (DGE), a common postoperative complication of pancreaticoduodenectomy, is not considered a life‐threatening complication. In the present study, we analyzed the risk factors for DGE and its impact on long‐term prognosis.

Possibility of sandwiched liver surgery with molecular targeting drugs, cetuximab and bevacizumab on colon cancer liver metastases: a case report

A 31-year-old man with sigmoid colon cancer with concomitant simultaneous multiple liver metastases had received FOLFIRI (leucovorin, fluorouracil and irinotecan) and FOLFOX6 (leucovorin, fluorouracil and oxaliplatin) after an ordinary sigmoidectomy. However, his serum carcinoembryonic antigen (CEA) level increased rapidly during the fifteen months after the operation while he was on FOLFOX6. Abdominal computed tomography revealed expanding multiple liver tumors. As the third line chemotherapy, a combination therapy of cetuximab with irinotecan was given, which markedly reduced his levels of serum CEA, and the size and number of liver tumors. He underwent lateral segmentectomy of the liver and microwave coagulation of the liver metastases in the remnant liver. Thereafter, a good quality of life with tumor dormancy was obtained for 6 months. However, his serum CEA started to rise again in the absence of liver tumors. Therefore, FOLFOX6 with bevacizumab was chosen as the fourth line chemotherapy, and the serum CEA was reduced with tumor dormancy. A good quality of life was obtained again at 3 years after the first surgery. This report indicates the effectiveness of sandwiched liver surgery with the molecular targeting drugs cetuximab and bevacizumab on multiple liver metastases of colon cancer, and suggests the possibility of a regimen consisting of bevacizumab following cetuximab.