Masanori Nishioka

Laparoscopic surgery reduces the risk of postoperative adhesion compared with open surgery. The aim of this study was to assess the advantage of laparoscopic surgery in terms of postoperative adhesion. Eleven patients participated in this study (laparoscopic surgery: 6 patients, open surgery: 5 patients). Body temperature, heart rate, the duration until the first postoperative flatus and the beginning of diet were investigated on postoperative day 0, 1, 3, and 5, respectively. Serum level of WBC and CRP, PAI-1 and IFN-gamma level in the drainage tube were also measured at the same time. There is no significant difference between the two groups in body temperature. The laparoscopic group revealed significantly lower WBC on POD 0 and CRP on POD 1 compared with the open group. PAI-1 was significantly lower on POD 3 and 5 in the laparoscopic group. IFN-gamma in the laparoscopic group tended to be suppressed compared with the open group. Laparoscopic surgery may decrease the risk of postoperative abdominal adhesion compared with open surgery by suppressing early postoperative inflammation.

Polysaccharide K (PSK) is widely used in Japan as a biological response modifier for cancer patients. We investigated the effects of PSK with S-1 based chemotherapy for advanced gastric cancer patients in immune response. Nine advanced gastric cancer patients who underwent chemotherapy at the University of Tokushima were included in this study. In all patients, 3g PSK was received orally and S-1 based chemotherapy for 2 weeks alternately for 8 weeks. Serial changes in immunological parameters (Foxp3, Natural killer (NK), CD4/CD8) were monitored. The levels of Foxp3 at 8 weeks was significantly decreased compared with 2 weeks (4.26% vs. 3.11%). In NK activity at 8 weeks was significantly increased compared with 2 weeks (27% vs. 47%). These results of this study suggested that chemotherapy with PSK improved the immune response in advanced gastric cancer patients. Especially Foxp3 was concerned in this mechanism.

The aim of this study was to investigate the impact of preoperative serum C-reactive protein (CRP) level as a prognostic indicator in patients with colorectal carcinoma (CRC). We investigated the correlation between preoperative CRP level and clinicopathological factors including prognosis of 167 patients who underwent resection for CRC retrospectively. Clinicopathological variables were compared between patients with serum CRP levels >1mg/dL (29 patients; high-CRP group) and patients with serum CRP levels <1mg/dL (138 patients; low-CRP group). In high-CRP group, 9 patients were stage I+II and 20 patients ware stage III+IV. In low-CRP group, 93 patients were stage I+II and 45 patients were stage III+IV. There were significant differences in the clinical stage, tumor diameter, curativity, final stage between the two groups (p<0.01). The overall survival and recurrence-free survival rates in high-CRP group were lower compared with the rates in low-CRP group (p<0.05 and p=0.14). In addition, the overall survival rate in stage I+II patients with high-CRP was significantly lower than that in patients with low-CRP (p<0.05). Using multivariate analysis, the preoperative elevation of serum CRP level was an independent prognostic factor in patients with CRC (p<0.05). We found that the preoperative elevation of serum CRP to be an independent prognostic indicator of CRC.

Laparoscopic skills training is becoming the standard for educating surgical residents. Because of the specific procedure which differs from that of open surgery, it is imperative to establish a unique training system to promote efficiency of learning laparoscopic skills. The aim of this study was to evaluate the efficiency of learning laparoscopic skills with or without authorized experts of JSES. Among 71 patients who underwent laparoscopic colectomy from 2004 to 2009, 30 patients who underwent operation in introduction era without a technical expert (2004-2006), 17 patients who underwent operation in late period of introduction era without a technical expert (2006-2008), 12 patients who underwent operation by resident with technical expert (2008-2009) and 12 patients who underwent operation by technical expert, were investigated. Operative time, amount of blood loss, intra- and post-operative complications and conversion to open surgery were investigated. Operative time: 477:333:262:220 minutes (early period:late period:resident:expert), amount of blood loss: 494:73:21:20mL and complications: ileus: 0:1:0:0, leakage: 1:1:3:0, neurological disturbance: 2:1:0:0. Instruction by authorized technical experts of JSES is helpful to avoid pitfalls which are not seen in open surgery without an expert.

The role of intratumoral thymidylate synthase (TS) mRNA or protein expression is still controversial and little has been reported regarding relation of them in colorectal cancer. Forty-six patients with advanced colorectal cancer who underwent surgical resection were included. TS mRNA expression was determined by the Danenberg tumor profile method based on laser-captured micro-dissection of the tumor cells. TS protein expression was evaluated using immunohistochemical staining. TS mRNA expression tended to relate TS protein expression. Statistical significance was not found in overall survival between the TS mRNA high group and low group regardless of performing adjuvant chemotherapy. The overall survival in the TS protein negative group was significantly higher than that in positive group in all and the patients without adjuvant chemotherapy. Multivariate analysis showed TS protein expression was as an independent prognostic factor. TS protein expression tends to be related TS mRNA expression and is an independent prognostic factor in advanced colorectal cancer.

Background/Aims: Preoperative chemoradiation therapy (CRT) for advanced rectal cancer allows anal sphincter preservation in some patients who would require an abdominoperineal resection. But adequate distal margin in patients with locally advanced rectal cancer requiring preoperative CRT is unclear. The objective was to evaluate necessary distal margin from reduced tumor by preoperative CRT for anal sphincter preservation. Methodology: This study included 11 consecutive patients who performed low anterior resection and abdominoperineal resection for rectal cancer after preoperative CRT. Distal margin length from reduced tumor by preoperative CRT to residual viable cancer, tumor grade, lymph-node-metastasis stage and pathological changes of tumors were examined. Results: Length from anal side edge of reduced tumor by preoperative CRT to pathological residual tumor ranged from +6mm to -9mm. Tumor stages were as follows: T0-2, NO, M0=3, T3, NO, M0=5, 14, NO, M0=1 and 13, NO, M+1=2. Median follow-up was 19 months. Recurrence occurred in one patient and was distant and not local. Pathological examinations showed that no patient had lymph-node-metastasis and residual tumors by preoperative CRT. Conclusions: This study suggests that for patients with locally advanced rectal cancer undergoing resection and preoperative CRT, distal margins >= 1cm from reduced tumor by preoperative CRT seem to compromise pathological outcome.

432 Background: Preoperative chemoradiotherapy (CRT) in rectal cancer reduces the local recurrence rate after operation and preserves the anus, but it is difficult to predict the effects of CRT. Our purpose of this study was to determine the effects and adverse events of CRT (S-1 or UFT) and to predict the response to CRT in rectal cancer by using both miRNA and DNA expression patterns. Methods: Rectal cancer patients (n=60) who underwent preoperative CRT were randomly divided into two groups (40Gy radiotherapy combined with S-1: 31 patients or UFT: 29 patients). The effects and adverse events of CRT were compared between S-1 group and UFT group. Additionally, RNA and DNA isolated from biopsy specimens of rectal cancer before preoperative CRT were hybridized to miRNA and DNA microarrays. Response to CRT was determined by histopathologic examination of surgically resected specimens. Results: Response to CRT determined by histopathologic examination of surgically resected specimens and RECIST were as follows: responders (grade 2 or 3) were 60%(S-1) and 52%(UFT) (p=0.52). Adverse events of CRT did not differ significantly between the 2 groups, and there was no adverse event of grade 3 or 4. As candidate predictive genes, 184 genes (S-1 group) and 193 genes (UFT group) were identified by DNA microarray, while 6 miRNA (S-1 group) and 16 miRNA (UFT group) were isolated by miRNA microarray as candidate predictive miRNA. Conclusions: Preoperative CRT using S-1 or UFT to rectal cancer is effective and the adverse events were acceptable. Expression profiling of both gene and miRNA may predict the effects of preoperative CRT, implicating the possible personalized therapy for patients with rectal cancer.

38 Background: The risk category of gastrointestinal stromal tumors (GIST) is usually determined by tumor size and mitotic count. Because of technical complexity and tumor heterogeneity in biopsy, accurate preoperative evaluation of malignant potential of GIST is very difficult. The aim of this study is to evaluate the utility of preoperative PET-CT examination for predicting the malignant potential of GIST. Methods: Ten patients with GIST who underwent preoperative PET-CT examination were enrolled. They were divided into two groups (low/intermediate-risk or high-risk) by risk category (tumor size, mitotic index). The relationships between the standardized uptake value (SUV) and GIST parameters including the size, mitotic index and Ki67 index were examined. Results: There was a significant correlation between the mitotic index and the SUV (p=0.029) but tumor size is not correlated with SUV. The SUV was significantly higher in the high-risk group (11.0 ± 3.04) than in the low/intermediate-risk group (2.1 ± 1.5). The Ki67 labeling index was also significantly higher in the high-risk group (8.63 ± 6.2) than in the low/intermediate-risk group (1.75 ± 0.52). There was a significant correlation between the Ki67 labeling index and the SUV (p=0.028). A mitotic index of 5/50 HPF was equivalent to an SUV of 4.3, and a Ki67 labeling index of 5 was equivalent to SUV of 6.3. SUV of 5 can predict the malignant potential between the high and low/intermediate risk. Conclusions: PET-CT can predict malignant potential. Cases with a high SUV, using a criterion of 5, might have malignant potential.

31 Background: Epigenetic modification by HDAC (histone deacetylase) plays important roles in the development and progression of cancer. It has been reported that CD133 positive cancer stem cells were induced through the HDAC → HIF-1α (Hypoxia Inducible Factor-1α) pathway, and Thrombospondin1 (THBS1) is associated with tumor angiogenesis. The aim of this study is to evaluate relationship between the HDAC, CD133, THBS1 and prognosis in gastric cancer. Methods: 65 patients of gastric cancer were enrolled in this study. HDAC1, CD133 and THBS1 expressions were evaluated in immunohistochemical (IHC) staining of surgical specimens. Relationship between the expressions of HDAC1, CD133, THBS1 and clinicopathological factors was investigated. Results: HDAC1-positive patients were 52% and had significantly poor prognosis compared with negative patients. There were more frequent liver metastasis and lymphatic invasion in positive patients. CD133-positive patients were 23.1% and had significantly poor prognosis compared with negative patients. There were more frequent depth wall invasion, distant metastasis, peritoneal recurrence. THBS1-positive patients were 26% and had significantly better prognosis compared with negative patients. In THBS1 positive patients, there was less lymph node metastasis, positive peritoneal cytology in ascites, distant metastasis and lymphatic invasion. CD133 expression is positively correlated with HDAC1. THBS1 expression revealed negative correlation with HDAC1. The survival rate of HDAC1 (+) / CD133 (+) group was significantly poor prognosis compared to the other group (HDAC1 (+) / CD133 (-), HDAC1 (-) / CD133 (+), HDAC1 (-) / CD133 (-)). HDAC1 (-) / THBS1 (+) group revealed significantly higher survival rate compared to the other group (HDAC1 (-) / THBS1 (+), HDAC1 (+) / THBS1 (+), HDAC1 (+) / THBS1 (-)). Conclusions: It was suggested that HDAC1 promoted CD133, suppressed THBS1 in gastric cancer and their interaction were increased the degree of malignancy.