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.

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.

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.

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.

The safety and usefulness of the single incision, transabdominal pre-peritoneal (TAPP) laparoscopic technique for inguinal hernia.

BACKGROUND: The safety and usefulness of the SILS-TAPP (transabdominal pre-peritoneal) procedure remain unclear. The aim of this study was to clarify the safety and usefulness of the SILS-TAPP procedure compared with standard laparoscopic TAPP and TEPP (totally extra-peritoneal pre-peritoneal) procedures. PATIENTS AND METHODS: 85 patients underwent laparoscopic inguinal hernia repairs (TEPP, 30 patients; TAPP, 20 patients; SILS-TAPP, 35 patients) from 2007 to 2011. The operative outcomes of the three groups were compared. RESULTS: There was no difference in the patients' characteristics among the three groups. The TEPP Group had a longer operation time. One patient in the SILS-TAPP group had an intraoperative complication. One patient in the TAPP group had a postoperative complication, and one patient had ileus and one had an umbilical hernia in the SILS-TAPP group. The postoperative hospital stay was not significantly different among the three groups. There were no recurrences in the TEPP group, 1 case of recurrence (5.0%) in the TAPP group, and 1 case (2.9%) in the SILS-TAPP group. CONCLUSIONS: The present findings show that the SILS-TAPP repair is safe and feasible for the repair of adult inguinal hernia.

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.

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.

The novel hypoxic cytotoxin, TX-2098 has antitumor effect in pancreatic cancer; possible mechanism through inhibiting VEGF and hypoxia inducible factor-1α targeted gene expression.

Tumor hypoxia has been considered to be a potential therapeutic target, because hypoxia is a common feature of solid tumors and is associated with their malignant phenotype. In the present study, we investigated the antitumor effect of a novel hypoxic cytotoxin, 3-[2-hydroxyethyl(methyl)amino]-2-quinoxalinecarbonitrile 1,4-dioxide (TX-2098) in inhibiting the expression of hypoxia inducible factor-1α (HIF-1α), and consequently vascular endothelial cell growth factor (VEGF) expression in pancreatic cancer. The antitumor effects of TX-2098 under hypoxia were tested against various human pancreatic cancer cell lines using WST-8 assay. VEGF protein induced pancreatic cancer was determined on cell-free supernatant by ELISA. Moreover, nude mice bearing subcutaneously (s.c.) or orthotopically implanted human SUIT-2 were treated with TX-2098. Tumor volume, survival and expression of HIF-1 and associated molecules were evaluated in treatment versus control groups. In vitro, TX-2098 inhibited the proliferation of various pancreatic cancer cell lines. In s.c model, tumors from nude mice injected with pancreatic cancer cells and treated with TX-2098 showed significant reductions in volume (P<0.01 versus control). Quantitative real-time reverse transcription-PCR analysis revealed that TX-2098 significantly inhibited mRNA expression of the HIF-1 associated molecules, VEGF, glucose transporter 1 and Aldolase A (P<0.01 versus control). These treatments also prolong the survival in orthotopic models. These results suggest that the effect of TX-2098 in pancreatic cancer might be correlated with the expression of VEGF and HIF-1 targeted molecules.

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.

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.

Platelet-derived endothelial cell growth factor/thymidine phosphorylase inhibitor augments radiotherapeutic efficacy in experimental colorectal cancer.

PURPOSES: A lot of radiosensitizers have been developed. However, there are few to be available in the clinical setting. Thymidine phosphorylase inhibitor (TPI) regulates the phosphorolysis of thymidine to thymine and 2-deoxy-d-ribose-1-phosphate which is essential for tumor angiogenesis. The aim of this study is to evaluate whether TPI augments the radiotherapy for colorectal cancer in vitro and in vivo studies. MATERIALS AND METHODS: The cytotoxicity of TPI with irradiation on HT29 and HCT116 cells was examined using MTT- and colony formation assay. At 10days post-inoculation, HT29 bearing orthotopic model mice (n=28) were divided into four groups and orally treated with TPI- (50mg/kg/day for 2weeks), radiation (RT, 2Gy×4: Total 8Gy), their combination or the vehicle. The mechanisms underlying the efficacy were assessed genomically and immunohistochemically. RESULTS: Compared to each single treatment, the combination of TPI and RT synergistically inhibited the cell viability in a time- and dose-dependent manner. In the HT-29 bearing mice, the combination of TPI and RT reduced the tumor growth compared with RT alone. Notably, the mRNA levels of VEGF, TGF-ß and, Rad51 and the protein expressions of VEGF and CD34 were significantly lower in the combination than the others. Furthermore, the combination markedly increased the TUNEL-positive cells, suggesting that TPI augments the cancer cell death through inhibition of angiogenesis and DNA repair system in the radiotherapy. CONCLUSIONS: Our study first demonstrated that the combination of TPI and irradiation was effective in colon cancer. TPI would provide a promising therapeutic strategy as a radiosensitizer.

Kampo medicine "Dai-kenchu-to" prevents CPT-11-induced small-intestinal injury in rats.

PURPOSE: The key anticancer agent, CPT-11 (irinotecan hydrochloride), induces severe diarrhea clinically. We investigated the effect of a Kampo medicine, Dai-kenchu-to (DKT), on CPT-11-induced intestinal injuries in rats. METHODS: Twenty-four male Wistar rats were divided into three groups: a control group; a CPT-11 group, given CPT-11 150 mg/kg intraperitoneally for 2 days; and a DKT group, given DKT 300 mg/kg orally for 5 days with CPT-11 150 mg/kg intraperitoneally on days 4 and 5. The rats were killed on day 6. RESULTS: Interleukin (IL)-1ß, IL-12, interferon (IFN)-γ, and tumor necrosis factor-α expression in the small intestine of the CPT-11 group was significantly higher than that of the control group. Interleukin-1ß and IFN-γ expression was improved significantly by DKT (P < 0.05). The number and height of jejuna villi, injury score, and apoptosis index in the CPT-11 group were improved significantly by DKT (P < 0.05). CONCLUSIONS: DKT suppressed CPT-11 induced inflammatory cytokines and apoptosis in the intestinal mucosa and maintained the mucosal integrity.

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.

The effects of the Kampo medicine (Japanese herbal medicine) "Daikenchuto" on the surgical inflammatory response following laparoscopic colorectal resection.

PURPOSES: The inflammatory response after surgery is associated with various postoperative complications. The aim of the present prospective study was to evaluate the effects of Daikenchuto (DKT) (a Japanese herbal medicine) on the inflammatory response in patients following laparoscopic colorectal resection. METHODS: Thirty patients who underwent laparoscopic colectomy for colorectal carcinoma were divided into two groups: a DKT intake group (D group, n = 15) and a control group (C group, n = 15). The D group took 7.5 g/day of DKT from the day after surgery until the 7th postoperative day. The body temperature, heart rate, WBC count, lymphocyte count, C-reactive protein (CRP) level, ß-D: -glucan level and Candida index were compared between the two groups. RESULTS: The patients' mean age in the D group was significantly younger than that in the C group. D3 lymph node dissection was performed more often in the D group. The time until first flatus was significantly shorter in the D group (1.8 ± 0.5 days) than in the C group (2.7 ± 0.5 days). The CRP level was significantly lower in the D group (4.6 ± 0.6 mg/dl) than in the C group (8.3 ± 1.1 mg/dl) on the 3rd postoperative day. CONCLUSIONS: Postoperative DKT administration significantly suppressed the CRP level and shortened the time until first flatus. DKT administration also significantly suppressed postoperative inflammation following surgery for colorectal cancer.

Evaluation of procedure of laparoscopic para-aortic lymph node biopsy: comparison between transperitoneal approach and extraperitoneal approach.

In gastrointestinal laparoscopic surgery, paraaortic lymphadenectomy is usually performed using a transperitoneal approach (TP), and the use of an extraperitoneal approach (EP) has been scarcely reported. Biopsy of the para-aortic lymph nodes was performed using TP with 3 ports on the patient with esophageal cancer, and EP lymphnode biopsy was performed with 4 ports with malignant lymphoma. The effect of TP vs. EP was evaluated regarding the intraoperative and postoperative complications. TP was difficult for massive biopsy, 1.5cm sized several lymph nodes along the common hepatic artery were biopsied. On the other hand, using EP a 5cm sized paraaortic lymph node was successfully performed. There was no difference between TP and EP in intraoperative blood loss and operation time, respectively, but EP showed great advantage with respect to postoperative complications and length of administration in hospital. Laparoscopic biopsy of para-aortic lymph nodes using EP is a useful method compared with the TP.

Malignant potential of Barrett's esophagus: special reference to HDAC-1 and MTA-1 expression.

BACKGROUND/AIMS: Barrett's esophagus is a major risk factor for esophageal adenocarcinoma. It is important to decide when and how to treat the patients with Barrett's esophagus (BE). It was reported that HDAC-1 (Histone Deacetylase-1) and MTA-1 (Metastasis-Associated Protein-1) were associated with initiation and progression of cancer. The aim of this study is to assess malignant potential of BE using the expression of HDAC-1 and MTA-1. METHODOLOGY: Seven BE cases with pathological specialized columnar epithelium and CK7/20 in an immunohistochemically positive state were selected from resected specimens of 23 patients with gastro-esophageal junction cancer. The expression of HDAC-1 and MTA-1 protein was evaluated using an immunohistochemical method. RESULTS: All seven cases with Barrett's esophagus were diagnosed as low grade dysplasia. Positive expression of HDAC-1 and MTA-1 was found in 0 out of 7 cases (0%) with normal esophageal epithelium, and 0 out of 7 cases (0%) with normal gastric epithelium. On the other hand, positive expression of both HDAC-1 and MTA-1 was found in 6 out of 7 (85.7%) cases with Barrett's epithelium and 7 out of 7 (100%) cases with gastro-esophageal-junction-cancer, respectively. CONCLUSION: Positive expression of HDAC-1 and MTA-1 was found even in low grade dysplasia. Therefore, BE with HDAC-1 and MTA-1 expression is considered to be a precancerous lesion re quiring curative treatment.

Visceral fat area is superior to body mass index as a predictive factor for risk with laparoscopy-assisted gastrectomy for gastric cancer.

INTRODUCTION: After adopting preoperative assessment of the perigastric vessels using 3D-CT and standardization of the procedures, obesity still influences smooth laparoscopy assisted gastrectomy (LAG). We evaluated the impact of body mass index (BMI) and area of visceral fat tissue on the risks of LAG. METHODS: Sixty-six patients who underwent LAG for gastric cancer were included. The patients were divided into two groups by BMI (<25 BMI-L group: n = 53; ≥25 BMI-H group: n = 13) and area of intraperitoneal fat tissue (<100 cm(2) AF-L group: n = 35; ≥100 cm(2) AF-H group: n = 31), respectively. Fat scan(®), which was computer software operating on abdominal CT, was used to measure the visceral fat areas (VFA). The incidence of postoperative complications, operation time, intraoperative blood loss, and number of dissected lymph nodes were compared between each two groups. RESULTS: The incidence of postoperative complications of BMI-L and BMI-H groups was 11.3% and 30%, respectively (p = 0.18). The mean blood loss was 85 and 134 g, respectively (p = 0.21). There were no significant differences in operation time and the number of retrieved LNs. The incidence postoperative complications (29%) and mean blood loss (148 g) of then VFA-H group were significantly higher than those of the VFA-L group (5.7%, 48 g). The number of retrieved LNs of the VFA-H group (n = 25) was significantly lower than that of the VFA-L group (n = 34). There was no significant difference in operation time. CONCLUSIONS: In the VFA-H group, the incidence of postoperative complications and intraoperative blood loss increased, and the dissected number of LNs decreased. The area of visceral fat tissue was useful to predict risks of LAG and postoperative complications with higher precision compared with BMI.

Expression of histone deacetylase 1 and metastasis-associated protein 1 as prognostic factors in colon cancer.

Histone deacetylase 1 (HDAC1) and metastasis-associated protein 1 (MTA1) form the nucleosome remodeling and histone deacetylation (NuRD) complex and may possibly play a central role in cancer development. However, limited data has been reported regarding the expression of both HDAC1 and MTA1. The aim of the present study was to clarify the clinical role of HDAC1 and MTA1 expression in colon cancer. Seventy-four patients with colon cancer, who underwent colectomy at our institution, were enrolled in this study. Expression of HDAC1 and MTA1 was examined immunohistochemically. The patients were divided into four groups: HDAC1-positive group (n=58), HDAC1-negative group (n=16), MTA1-positive group (n=38) and MTA1-negative group (n=36). Clinicopathological factors and survival rates were compared between the groups. Regarding the clinicopathological factors, the depth of tumor invasion and stage correlated significantly with HDAC1 expression (p<0.05). Age, depth of tumor invasion and vascular invasion tended to correlate with MTA1 expression. The 5-year survival rate in the HDAC1-positive group (55.1%) was significantly worse compared to the HDAC1-negative group (86.5%) (p<0.05), and the 5-year survival rate of the MTA1-positive group (50.5%) was significantly worse than that of the MTA1-negative group (73.1%) (p=0.05). In patients with stages II-IV and curability A, B, the survival rate in those with HDAC1-positive expression was significantly worse than those with HDAC1-negative expression (p<0.05), and the survival rate of the MTA1-positive group tended to be worse than that of the MTA1-negative group (p=0.07). Overall survival in both the HDAC1 and MTA1-positive groups was significantly worse than overall survival of the other groups (p<0.05). Disease-free survival in both the HDAC1- and MTA1-positive groups, among patients with stages II-IV and curability A, B, was also significantly worse than that of the other groups (p<0.05). HDAC1 and MTA1 expression levels were significantly related to poorer prognosis. Therefore, HDAC1 and MTA1 expression levels are potential prognostic indicators for colon cancer.

Gene expression profile can predict pathological response to preoperative chemoradiotherapy in rectal cancer.

BACKGROUND: Preoperative chemoradiotherapy (CRT) has been widely used to improve local control of disease and to preserve the anal sphincter in the treatment of rectal cancer. However, the response to CRT differs among individual tumors. Our purpose of this study was to identify a set of discriminating genes that can be used for characterization and prediction of response to CRT in rectal cancer. PATIENTS AND METHODS: Seventeen rectal cancer patients who underwent preoperative CRT (40 Gy radiotherapy combined with S-1) were studied. Biopsy specimens were obtained from rectal cancer patients before preoperative CRT and were analyzed by focused DNA microarray (132 genes) and immunohistochemistry. Response to CRT was determined by histopathologic examination of surgically resected specimens and patients were classified as responders (grade 2 or 3) or non-responders (grade 0 or 1). RESULTS: Of the 17 samples, 10 were classified as responders and 7 as non-responders. Seventeen genes were differentially expressed at significant levels (p<0.05) between responders and non-responders. All genes showed higher expression in responders as compared with non-responders. The list of discriminating genes included matrix metalloproteinase- (MMP), apoptosis- (nuclear factor kappa light polypeptide gene enhancer in B-cells 2 (NFKB2), transforming growth factor beta 1 (TGFB1)), DNA repair- (topoisomerase 1 (TOP1)), and cell proliferation (integrin, beta 1 (ITGB1))-related genes. In the immunohistochemistry of MMP7, 4 responders were judged as showing overexpression of MMP7. On the other hand, none of the non-responders were judged as showing overexpression of MMP7. CONCLUSION: Gene expression patterns of diagnostic biopsies can predict pathological response to preoperative CRT with S-1 in rectal cancer.