TU-100 exerts a protective effect against bacterial translocation by maintaining the tight junction.

PURPOSE: We previously reported that TU-100 suppresses irinotecan hydrochloride (CPT-11)-induced inflammatory cytokines and apoptosis. However, the mechanism underlying this effect has not been fully elucidated. The aim of this study was to further clarify the mechanism of CPT-11-induced bacterial translocation (BT) and the effect of TU-100 on BT. METHODS: Cell cytotoxicity was assessed in vitro by a WST-8 assay. For the in vivo experiments, rats were randomly divided into 3 groups: the control group, the CPT-11 group (250 mg/kg i.p. for 2 days), and the CPT-11 and TU-100 co-treated group (1000 mg/kg, p.o. for 5 days). All of the rats were sacrificed on day 6 and their tissues were collected. RESULTS: CPT-11 and TU-100 co-treatment improved CPT-11 the related cytotoxicity in vitro. All CPT-11-treated rats developed different grades of diarrhea and BT was observed in 80% of the rats. CPT-11 caused a significant increase in the expression of TLR4, IL-6, TNF-α, IL-1ß and caspase-3 mRNAs in the large intestine. The expression of tight junction (TJ) marker mRNAs (occludin, claudin-1 and 4, and ZO-1) was significantly decreased in comparison to the control group. TU-100 co-treatment significantly reversed diarrhea, BT, and the expression of TLR2, IL-6, TNF-α, IL-1ß and caspase-3, and improved the expression of occludin, claudin-4 and ZO-1. CONCLUSIONS: TU-100 can suppress the adverse effects associated with CPT-11 and improve the function of the TJ. It is possible that this occurs through the TLR pathway.

Risk Model for Distal Gastrectomy When Treating Gastric Cancer on the Basis of Data From 33,917 Japanese Patients Collected Using a Nationwide Web-based Data Entry System.

OBJECTIVE: To establish a risk model for distal gastrectomy in Japanese patients with gastric cancer. BACKGROUND: Risk stratification for distal gastrectomy in Japanese patients with gastric cancer improves surgical outcomes. METHODS: The National Clinical Database was constructed for risk determination in gastric cancer-related gastrectomy among Japanese individuals. Data from 33,917 gastric cancer cases (1737 hospitals) were used. The primary outcomes were 30-day and operative mortalities. Data were randomly assigned to risk model development (27,220 cases) and test validation (6697 cases) subsets. Stepwise selection was used for constructing 30-day and operative mortality logistic models. RESULTS: The 30-day, in-hospital, and operative mortality rates were 0.52%, 1.16%, and 1.2%, respectively. The morbidity was 18.3%. The 30-day and operative mortality models included 17 and 21 risk factors, respectively. Thirteen variables overlapped: age, need for total assistance in activities of daily living preoperatively or within 30 days after surgery, cerebrovascular disease history, more than 10% weight loss, uncontrolled ascites, American Society of Anesthesiologists score (≥ class 3), white blood cell count more than 12,000/µL or 11,000/µL, anemia (hemoglobin: males, <13.5 g/dL; females, <12.5 g/dL; or hematocrit: males, <37%; females <32%), serum albumin less than 3.5 or 3.8 g/dL, alkaline phosphatase more than 340 IU/L, serum creatinine more than 1.2 mg/dL, serum Na less than 135 mEq/L, and prothrombin time-international normalized ratio more than 1.25 or 1.1. The C-indices for the 30-day and operative mortalities were 0.785 (95% confidence interval, 0.705-0.865; P < 0.001) and 0.798 (95% confidence interval, 0.746-0.851; P < 0.001), respectively. CONCLUSIONS: The risk model developed using nationwide Japanese data on distal gastrectomy in gastric cancer can predict surgical outcomes.

Duodenal-jejunal bypass improves diabetes and liver steatosis via enhanced glucagon-like peptide-1 elicited by bile acids.

BACKGROUND AND AIM: Bariatric surgery not only elicits weight loss but also rapidly resolves diabetes. However, the mechanisms remain unclear. The present study investigates how diabetes and liver steatosis are improved after duodenal-jejunal bypass (DJB) compared with a glucagon-like peptide-1 (GLP-1) analog and correlations between bile acids and GLP-1 secretion. METHODS: We initially determined the effects of bile acids on GLP-1 in vitro and then assigned 12 male 16-week-old Otsuka Long-Evans Tokushima Fatty rats to groups that underwent DJB, a sham operation, or were treated with the GLP-1 receptor agonist, liraglutide (n = 4 each). Blood glucose, insulin, GLP-1, serum bile acids, liver steatosis, and the number of GLP-1 positive cells (L cells) in the small intestine and colon were investigated in the three groups at eight weeks postoperatively. RESULTS: Levels of GLP-1mRNA were upregulated and GLP-1 secretion increased in cells incubated with bile acids in vitro. Weight gain was suppressed more in the DJB than in the sham group in vivo. Diabetes was more improved and GLP-1 levels were significantly higher in the DJB than in the sham group. Serum bile acids were significantly increased, the number of L cells in the ileum was upregulated compared with the sham group, and liver steatosis was significantly improved in the DJB compared with the other two groups. CONCLUSIONS: Duodenal-jejunal bypass might improve diabetes and liver steatosis by enhancing GLP-1 secretion through increasing serum bile acids and the proliferation of L cells in the ileum, compared with liraglutide.

Phase I trial of neoadjuvant preoperative chemotherapy with S-1, oxaliplatin, and bevacizumab plus radiation in patients with locally advanced rectal cancer.

BACKGROUND: This phase I study was performed to determine the maximum tolerated dose (MTD), recommended dose (RD), and dose-limiting toxicities (DLTs) of oxaliplatin combined with preoperative chemoradiotherapy with S-1, oxaliplatin, and bevacizumab in locally advanced rectal cancer. METHODS: Eligible patients had a newly diagnosed clinical stage T1-4 N0-3 M0 rectal adenocarcinoma within 12 cm of the anal verge suitable for curative resection. Conformal radiation therapy was given (4 fields, 2 Gy daily fractions, 5 days/week, total dose 40 Gy) with concurrent S-1 (80 mg/m(2)/day orally, days 1-5, 8-12, 15-19, and 22-26), bevacizumab (90 min continuous intravenous infusion at 5 mg/kg, days 1 and 15), and oxaliplatin (120 min continuous intravenous infusion, days 1, 8, 15, and 22). The initial oxaliplatin dose (40 mg/m(2)/day) was gradually increased to determine the MTD and RD. Surgery was performed 6 weeks after completion of preoperative chemoradiotherapy. RESULTS: 11 patients were enrolled. The MTD of oxaliplatin was considered to be 60 mg/m(2), because three of five patients developed DLTs such as diarrhea and hives. The recommended dose of oxaliplatin was set at 50 mg/m(2). Of the patients who received oxaliplatin at ≤ RD, 5 (83.3%) had a clinical response [four pathological responses and one pathological complete response (Grade 3)]. CONCLUSIONS: With this new regimen, the MTD of oxaliplatin was 60 mg/m(2), and the RD for phase II studies was 50 mg/m(2). This new regimen appears to provide worthwhile outcomes for locally advanced rectal cancer and merits a phase II study.

Protein kinase Cι is a new prognostic factor in gastric cancer.

PURPOSES: Protein kinase Cι (PKCι) is an important oncogenic K-ras effector, and its expression is correlated with tumor angiogenesis. The role of PKCι in gastric cancer remains unclear. The aim of this study was to clarify the role of PKCι in gastric cancer. METHODS: Twenty-eight patients with gastric cancer who underwent gastrectomy were enrolled in this study. The expression of PKCι mRNA was determined, as were the clinicopathological factors. The patients were divided into PKCι high and low expression groups. The 5-year survival rate, ERK mRNA level and VEGF mRNA level were compared between the two groups. The prognostic factors were investigated by a multivariate analysis. RESULTS: High expression of PKCι was observed to be associated with a lack of differentiation, tumor invasion ≥muscularis propria≤, stage III and IV disease and peritoneal dissemination. The 5-year survival rate in the PKCι high group was lower than that in the PKCι low group. The multivariate analysis revealed that a high expression level of PKCι was an independent prognostic factor. The expression levels of ERK and VEGF in the PKCι high group were higher than those in the PKCι low group. CONCLUSION: Our results indicate that PKCι is correlated with tumor progression and angiogenesis. PKCι may be a new prognostic factor for gastric cancer.

Characteristics of internal hernia after gastrectomy with Roux-en-Y reconstruction for gastric cancer.

BACKGROUND: Although the internal hernias have been a huge topic in the field of bariatric surgery, there were a few reports in gastric cancer. The purpose of this study was to analyze the incidence, clinical features, and prevention of internal hernia after gastrectomy for gastric cancer. METHODS: Twelve patients who underwent surgical treatment for internal hernia in our hospital after gastrectomy were analyzed. Features, including incidence, symptoms, and signs, were investigated in detail. RESULTS: The operative procedures for preceding gastrectomies were open distal gastrectomy in three patients, open total gastrectomy in three patients, laparoscopic-assisted distal gastrectomy in two patients, and laparoscopic total gastrectomy in four patients. The most frequent sites of internal hernias were jejunojejunostomy mesenteric defects (five patients) and Petersen's defect (five patients), mesenterium of transverse colon (one patient), and esophagus hiatus (one patient). There was no significant difference between open and laparoscopic preceding gastrectomies. After closure of the mesenteric defect was introduced, no further internal hernias occurred. On CT examination, the whirl sign was present in ten patients on 3D images. CONCLUSIONS: The present data suggest the importance of early recognition and treatment of internal hernia, as well as its prevention by closure of mesenteric defects.

CD133 expression is correlated with poor prognosis in colorectal cancer.

BACKGROUND/AIMS: Cancer stem cells (CSC) was reported to play an important role in various kinds of cancer. CD133 is one of the cancer stem cell markers in solid cancers. However, the correlation between CD133 expression and the clinicopathological factors in colorectal cancer (CRC) remains unclear. METHODOLOGY: Forty patients with CRC who underwent operations were enrolled. Expression of CD133 was investigated by immunohistochemistry (IHC). The staining was observed in the cytoplasm of cancer cells and the patients who have the staining were defined as CD133-positive cases. The patients were divided into two groups: the CD133-positive group (n = 22) and negative group (n = 18). Clinicopathological factors were compared between the two groups. The prognostic factors were investigated by multivariate analysis. RESULTS: In the CD133-positive group, the incidence of lymph node and liver metastasis, lymphatic and venous invasion, as well as the progression of stage of cancer were higher than that in the CD133-negative group. The 5-year survival rate and the disease-free survival rate in the CD133-positive group were lower than that in the CD133-negative group. The multivariate analysis revealed that CD133 expression tended to be an independent prognostic factor. CONCLUSIONS: CD133 expression is correlated with poor prognosis in CRC.

Comparisons of inflammatory cytokines expressions in drain after laparoscopic versus open surgery.

BACKGROUND/AIMS: 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. METHODOLOGY: 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. RESULTS: 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. CONCLUSIONS: Laparoscopic surgery may decrease the risk of postoperative abdominal adhesion compared with open surgery by suppressing early postoperative inflammation.

Duodenal-Jejunal Bypass Improves Insulin Resistance by Enhanced Glucagon-Like Peptide-1 Secretion Through Increase of Bile Acids.

BACKGROUND/AIMS: The aim of this study is to investigate the mechanisms of improvement in insulin resistance after duodenal-jejunal bypass (DIB), especially regarding the correlation between bile acids and glucagon-like peptide-1 (GLP-1). METHODOLOGY: SD rats were divided into two groups: DIB or Sham group. Blood glucose, insulin, GLP-1, bile acids, and the number of L cells in the small intestine were investigated three weeks after the operations. Next, to assess the effect of the bile acids on GLP-1 secretion in ileum, bile diversion model (=inhibition of rapid bile exposure to the ileum; BD group) were performed and postoperative glycemic parameters were measured. RESULTS: DJB improved insulin resistance and increased GLP-1 compared with sham. Higher bile acids in DJB were found than that in sham. The number of L cells in the common limb of DJB was increased compared with that in the distal segment of sham. In BD group, insulin resistance had not improved. GLP-1, bile acids, and the number of L cells revealed no significant changes compared with sham. CONCLUSIONS: DJB has a potential to improve insulin resistance, which may be related to enhanced GLP-1 secretion through the increase of bile acids in the common limb of the small intestine.

Survivin expression can predict the effect of chemoradiotherapy for advanced lower rectal cancer.

BACKGROUND: Chemoradiotherapy (CRT) has been used to improve local control and survival in patients with advanced rectal carcinoma. However, a significant proportion of patients show poor response to adjuvant CRT. We thus investigated the usefulness of survivin expression as a predictive marker of the CRT response and its characteristics. METHODS: Forty-three patients with lower rectal cancer who underwent CRT were investigated. All patients received preoperative CRT consisting of TS-1 concurrent with 40 Gy of pelvic irradiation followed by curative resection. The relationship between clinical response, or pathological response, and the expression of survivin of pre-CRT biopsy specimens was evaluated by immunohistochemistry and compared with post-CRT expression. RESULTS: Positive expression of survivin was observed in 26 of 43 patients (60%) in pre-CRT specimens. Survivin was positively expressed in 77% of stable disease cases, and 43% of partial response (p < 0.05). Regarding the correlation between pathological response and survivin expression, positive expression of survivin was recognized in 75% (18 of 24) of Grade 0 + 1 cases, 50% (7 of 14) of Grade 2 cases, and 20% (1 of 5) of Grade 3 cases. A reverse correlation was recognized between pathological responses and survivin expression (p < 0.05). There were differences in the tumor differentiation between the survivin-positive group and the negative group (p < 0.05). The expression concordance rate was 66% between pre- and post-CRT tissues. In post-CRT tissues, nuclear survivin expression disappeared completely and cytoplasmic expression increased, especially in responder cases. CONCLUSION: Survivin expression in biopsy could be an important predictive factor of preoperative CRT response.

Impact of C-reactive protein on prognosis of patients with colorectal carcinoma.

BACKGROUND/AIMS: 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). METHODOLOGY: 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). RESULTS: 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). CONCLUSIONS: We found that the preoperative elevation of serum CRP to be an independent prognostic indicator of CRC.

The effect of polysaccharide k with S-1 based chemotherapy in advanced gastric cancer.

BACKGROUND/AIMS: 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. METHODOLOGY: 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. RESULTS: 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%). CONCLUSIONS: 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.

Efficacy of PET-CT for predicting the malignant potential of gastrointestinal stromal tumors.

PURPOSES: Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the intestinal tract. The risk category is usually determined by tumor size and mitotic count, but accurate preoperative diagnosis of GIST is very difficult. The purpose of this study is to evaluate the efficacy of positron emission tomography (PET)-CT for predicting the malignant potential of gastrointestinal stromal tumors. METHODS: Ten patients with GIST who underwent a preoperative PET-CT examination were divided into two groups by risk category, and various factors were compared between the two groups. The relationships between the maximum standardized uptake value (SUVmax) and GIST parameters were examined. RESULTS: Patients were classified into two groups by their risk category: (low/intermediate-risk or high-risk). The SUVmax 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 SUVmax (p = 0.028) and between the mitotic index and the SUVmax (p = 0.029). CONCLUSIONS: PET-CT can predict malignant potential. Cases with a SUVmax of over 5 may have malignant potential.

Irinotecan injures tight junction and causes bacterial translocation in rat.

BACKGROUND: Tight junctions are an essential component of intestinal epithelial barriers. Claudin-1, occludin, and ZO-1 are the components of tight junction. The purpose of this study was to investigate whether irinotecan induces bacterial translocation in rats, and thus elucidate the relationship between tight junction and bacterial translocation. METHODS: Ten rats were divided into two groups: Five were treated with irinotecan and five were not treated with irinotecan, the control group. Irinotecan treated rats were administrated irinotecan 250 mg/kg intraperitoneally on days designated 0 and 1, were then killed at 48 h after treatment, and tissues were collected for analysis. Controls were treated with a saline solution. RESULTS: In eighty percent of irinotecan treated rats, bacteria were detected in the mesenteric lymph node or spleen. Large intestinal resistance of the rats was decreased. On the contrary, small intestinal resistance increased. Claudin-1 protein expression of both the small and large intestine decreased (P < 0.05), occludin protein expression of the small intestine decreased (P < 0.05), and occludin protein expression of the large intestine had decreasing tendency (P = 0.07) in irinotecan treated rats. In irinotecan treated rats, claudin-1 mRNA of the small intestine decreased (P < 0.05), claudin-1 mRNA of large intestine had a tendency to decrease (P = 0.05), occludin mRNA of both small and large intestine decreased (P < 0.05). CONCLUSIONS: Irinotecan injures claudin-1 and occludin. It causes disorders in the intestinal epithelial barrier and induces bacterial translocation.

Comparison of long-term prognosis of laparoscopy-assisted gastrectomy and conventional open gastrectomy with special reference to D2 lymph node dissection.

BACKGROUND: Laparoscopy-assisted gastrectomy (LAG) is becoming widely used for early gastric cancer. However, how the curability and long-term prognosis of LAG and open gastrectomy (OG) for early and advanced gastric cancer compare remains unclear. This study assessed short- and long-term outcomes after LAG with lymph node dissection in early and advanced gastric cancer. METHODS: A total of 332 patients who underwent LAG or OG for early and advanced gastric cancer from January 2001 through December 2010 were reviewed retrospectively. The mean operating time, estimated mean blood loss, number of dissected lymph nodes, and survival rates were compared between LAG and OG for early and advanced gastric cancer. RESULTS: Overall, 47.6% (158/332) of patients underwent LAG; D1, D1+ lymph node dissection was carried out in 77.2%, with D2 dissection in 22.8%. Only one patient required conversion to OG. Comparing LAG and OG with D1, D1+ lymph node dissection for early gastric cancer (EGC), mean operating time was significantly longer, estimated mean blood loss was significantly smaller, and the average number of retrieved lymph nodes was significantly greater with LAG. The rate of specific postoperative morbidity was 17.2% for LAG patients and 25.0% for OG patients, with no postoperative mortality. Survival and recurrence rates were not significantly different. Comparing LAG and OG with D2 lymph node dissection for advanced gastric cancer (AGC), mean operating time was significantly longer and estimated mean blood loss was significantly smaller with LAG, while the average number of retrieved lymph nodes, specific postoperative morbidity and mortality, and survival and recurrence rates were not significantly different. CONCLUSIONS: LAG with D1, D1+ lymph node dissection for EGC is safe and equivalent to open gastrectomy in curability. Moreover, LAG with D2 lymph node dissection for AGC is comparable to OG with D2 lymph node dissection with regard to short- and long-term results.

Clinicopathological analysis of distal margin for rectal cancer after preoperative chemoradiation therapy.

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 +6 mm to -9 mm. Tumor stages were as follows: T0-2, N0, M0=3, T3, N0, M0=5, T4, N0, M0=1 and T3, N0, 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 ≥1 cm from reduced tumor by preoperative CRT seem to compromise pathological outcome.

Thymidylate synthase (TS) protein expression as a prognostic factor in advanced colorectal cancer: a comparison with TS mRNA expression.

BACKGROUND/AIMS: 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. METHODOLOGY: 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. RESULTS: 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. CONCLUSIONS: TS protein expression tends to be related TS mRNA expression and is an independent prognostic factor in advanced colorectal cancer.

Preoperative radiotherapy combined with S-1 for advanced lower rectal cancer: phase I trial.

BACKGROUND/AIMS: S-1 based chemoradiation is the recommended treatment for rectal cancer; however, the optimal scheduling and dosing are not yet established. A Phase I study was conducted to determine the maximum tolerated dose (MTD) of S-1 with radiotherapy (RT). Endpoints were the toxicity profile of this regimen and to determine the recommended dose (RD). METHODOLOGY: Conformal RT was given using 4 fields at daily fractions of 2Gy on 5 days per week to a total dose of 40Gy. Concurrently S-1 was given twice daily throughout RT. Eligible patients had a newly diagnosed clinical stage T3-4 N0-2 M0 rectal adenocarcinoma located within 12cm of the anal verge suitable for curative resection. Surgery was performed 6 weeks from completion of preoperative chemoradiotherapy. The dose escalating from S-1 80mg/m2/day (Level 1) to 100mg/m2/day (Level 2). RESULTS: Nine patients were valid for safety. In all patients, S-1 was administered. There was no dose-limiting toxicity (DLT) in patients treated at dose Level 1. Six patients were enrolled in the dose-escalation phase. At dose Level 2, two patients developed DLT and this was considered the MTD. Objective response according to RECIST were observed in 5 of 9 patients who had measurable disease (56%). CONCLUSIONS: The RD of S-1 with concurrent RT was determined to be 80mg/m2/day. Preoperative RT combined with S-1 was feasible and well tolerated.

Impact of education with authorized technical experts on colorectal laparoscopic skills.

BACKGROUND/AIMS: 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. METHODOLOGY: 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. RESULTS: 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. CONCLUSIONS: Instruction by authorized technical experts of JSES is helpful to avoid pitfalls which are not seen in open surgery without an expert.

Evaluation of relation of RAD51 and the effect of chemo-radiation therapy for advanced rectal cancer.

BACKGROUND/AIMS: Chemo-radiation therapy (CRT) has been used to improve local control and survival in patients with advanced rectal carcinoma. However, a significant proportion of patients shows poor response to adjuvant CRT. We thus investigated the usefulness of RAD51 expressions as a predictive maker of the CRT response. METHODOLOGY: Forty two patients who suffered from lower rectal cancer were investigated. All patients received preoperative CRT consisting of TS-1, concurrent with 40Gy of pelvic irradiation before having curative radical resection. The relationship between pathological responses of the tumors after therapy and expression of RAD51 was evaluated by immunostaining of resected specimen. RESULTS: Positive expression of RAD51 was observed in 24 of 42 patients (57.1%). RAD51 positively expressed in 68.2% (15 of 22 cases) of SD and 42.2% (9 of 20 cases) of PR and CR. There is a tendency of reverse correlation between clinical response and expression of RAD51. Regarding the correlation between pathological response and RAD51 expression, positive expression of RAD51 was recognized in 75.0% (15 of 20 cases) of Grade 1, 47.1% (8 of 17 cases) of Grade 2 and 20.0% (1 of 5 cases) of Grade 3. A significant reverse correlation was recognized between RAD51 expression and pathological responses. CONCLUSIONS: RAD51 expression could be one of the most important predictive factors of preoperative CRT for advanced lower rectal cancer.