Oncological outcomes of complete versus conventional mesocolic excision in laparoscopic right hemicolectomy.

BACKGROUND: Complete mesocolic excision (CME) has been proposed for colon cancer to improve oncological outcomes. The risks and benefits of laparoscopic CME have not been examined fully. We compared short- and long-term outcomes of CME with a conventional mesocolic excision (non-CME) in laparoscopic right hemicolectomy (RHC) for right-sided colon cancer. METHODS: In total, 115 patients who underwent laparoscopic RHC with stage I-III right-sided colon cancer at Busan Paik Hospital from August 2007 to October 2011 were enrolled in this case-control study. Three trained colorectal surgeons reviewed videos of the surgeries; patients were divided into two groups: those who underwent a CME (CME group, n = 34) and those who underwent a conventional mesocolic excision (non-CME group, n = 81). RESULTS: There was no significant difference between the CME and non-CME groups in operative time, post-operative complications, or hospital stay. However, the CME group had more lymph nodes harvested (P < 0.001) and lower blood loss (P = 0.016) versus the non-CME group. There was no difference in 5-year disease-free survival rate between the groups, but 5-year overall survival rate was 100% in the CME group and 89.49% in the non-CME group (P < 0.05). CONCLUSIONS: Laparoscopic RHC with CME is safe and associated with better 5-year overall survival rate than non-CME for patients with stage I-III right-sided colon cancer. Implementation of CME surgery might improve oncological outcomes for patients with right-sided colon cancer.

Prognostic value of positron emission tomography/computed tomography for adjuvant chemotherapy of colon cancer.

BACKGROUND: To assess the prognostic value of preoperative 18 F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with high-risk stage II or stage III colon cancer who underwent FOLFOX chemotherapy. METHODS: The study included 166 patients with high-risk stage II or stage III colon cancer who received FOLFOX4 chemotherapy. Retrospective patient data were analysed including pathological stage, histology, disease-free survival (DFS) and the maximum standardized uptake value (SUVmax ) of the primary tumour on 18 F-fluorodeoxyglucose positron emission tomography/computed tomography. The primary end point was DFS. RESULTS: There were recurrences in 29 of the 166 patients (17.4%). Measuring the area under the receiver operating characteristic curve, the cut-off value of SUVmax with maximum sensitivity and specificity was 10.95. Using the Kaplan-Meier method, the DFS of the patients categorized by SUVmax tended to differ (P = 0.055). In univariate analyses, the risk factors for DFS were age over 70 years, higher N stage and neural invasion. SUVmax ≤ 10.95 showed a tendency, but was not significant (P = 0.0604). In multivariate analyses, the risk factors for DFS were age over 70 and neural invasion. CONCLUSIONS: The results of this study suggest that high fluorodeoxyglucose uptake of the primary mass in high-risk stage II and stage III colon cancer does not significantly correlate with DFS.

Difference in Tumor Area as a Predictor of a Pathological Complete Response for Patients With Locally Advanced Rectal Cancer.

PURPOSE: This study was conducted to discover the clinical factors that can predict pathologically complete remission (pCR) after neoadjuvant chemoradiotherapy (CRT), so that those factors may help in deciding on a treatment program for patients with locally advanced rectal cancer. METHODS: A total of 137 patients with locally advanced rectal cancer were retrospectively enrolled in this study, and data were collected retrospectively. The patients had undergone a total mesorectal excision after neoadjuvant CRT. Histologic response was categorized as pCR vs. non-pCR. The tumor area was defined as (tumor length) × (maximum tumor depth). The difference in tumor area was defined as pre-CRT tumor area - post-CRT tumor area. Univariate and multivariate logistic regression analyses were conducted to find the factors affecting pCR. A P-value < 0.05 was considered significant. RESULTS: Twenty-three patients (16.8%) achieved pCR. On the univariate analysis, endoscopic tumor circumferential rate <50%, low pre-CRT T & N stage, low post-CRT T & N stage, small pretreatment tumor area, and large difference in tumor area before and after neoadjuvant CRT were predictive factors of pCR. A multivariate analysis found that only the difference in tumor area before and after neoadjuvant CRT was an independent predictor of pCR (P < 0.001). CONCLUSION: The difference in tumor area, as determined using radiologic tools, before and after neoadjuvant CRT may be important predictor of pCR. This clinical factor may help surgeons to determine which patients who received neoadjuvant CRT for locally advanced rectal cancer should undergo surgery.

The Prognostic Value of Circumferential Resection Margin Involvement in Patients with Extraperitoneal Rectal Cancer.

The prognostic influence of circumferential resection margin (CRM) status in extraperitoneal rectal cancer probably differs from that of intraperitoneal rectal cancer because of its different anatomical and biological behaviors. However, previous reports have not provided the data focused on extraperitoneal rectal cancer. Therefore, the aim of this study was to examine the prognostic significance of the CRM status in patients with extraperitoneal rectal cancer. From January 2005 to December 2008, 248 patients were treated for extraperitoneal rectal cancer and enrolled in a prospectively collected database. Extraperitoneal rectal cancer was defined based on tumors located below the anterior peritoneal reflection, as determined intraoperatively by a surgeon. Cox model was used for multivariate analysis to examine risk factors of recurrence and mortality in the 248 patients, and multivariate logistic regression analysis was performed to identify predictors of recurrence and mortality in 135 patients with T3 rectal cancer. CRM involvement for extraperitoneal rectal cancer was present in 29 (11.7%) of the 248 patients, and was the identified predictor of local recurrence, overall recurrence, and death by multivariate Cox analysis. In the 135 patients with T3 cancer, CRM involvement was found to be associated with higher probability of local recurrence and mortality. In extraperitoneal rectal cancer, CRM involvement is an independent risk factor of recurrence and survival. Based on the results of the present study, it seems that CRM involvement in extraperitoneal rectal cancer is considered an indicator for (neo)adjuvant therapy rather than conventional TN status.

Clinical Practice in the Use of Adjuvant Chemotherapy for Patients with Colon Cancer in South Korea: a Multi-Center, Prospective, Observational Study.

BACKGROUND: Adjuvant chemotherapy is a crucial part of treatment for patients with locally advanced colon cancer. This study was conducted to investigate the actual practice in the use of adjuvant chemotherapy for patients with high-risk stage II or stage III colon cancer in South Korea. METHODS: This was a 24-month open-label, prospective, observational study conducted at 12 centers across South Korea. Patients with high-risk stage II and stage III colon cancer receiving adjuvant chemotherapy after curative surgery were included, and data were collected at baseline, third, and sixth month. RESULTS: A total of 246 patients were included in the analyses. Of five available regimens (FOLFOX, CAPOX, 5-FU/LV, capecitabine, and UFT/LV), FOLFOX was most commonly used (82.5%). Investigators indicated the "efficacy" as the major cause for selecting FOLFOX or CAPOX. For 5-FU/LV, capecitabine, or UFT/LV, the "safety" or "patient's characteristics (age, comorbidity, and stage)" was one of the most important selecting factors. Patients receiving 5-FU/LV, capecitabine, or UFT/LV had older age, worse PS and lower disease stage (stage II) than patients receiving FOLFOX or CAPOX. Hematologic toxicities were the most common cause of dose adjustment and treatment delay. CONCLUSIONS: In South Korea, FOLFOX was the most commonly used regimen for adjuvant chemotherapy and its efficacy was the main cause for selecting this regimen. Patients receiving 5-FU/LV, capecitabine, or UFT/LV had older age, worse PS and lower disease stage (stage II) than patients receiving FOLFOX or CAPOX.

ERCC1 as a Predictive Marker for FOLFOX Chemotherapy in an Adjuvant Setting.

PURPOSE: The purpose of this study was to identify the excision repair cross-complementation group 1 (ERCC1) as a predictive marker for FOLFOX adjuvant chemotherapy in stages II and III colon cancer patients. METHODS: A total of 166 high risk stages II and III colon cancer patients were retrospectively enrolled in this study, and data were collected prospectively. They underwent a curative resection followed by FOLFOX4 adjuvant chemotherapy. We analyzed ERCC1 expression in the primary colon tumor by using immunohistochemical staining. The oncological outcomes included the 5-year disease-free survival (DFS) rate. The DFS was analyzed by using the Kaplan-Meier method with the log-rank test. A Cox proportional hazard model was used for the prognostic analysis. RESULTS: ERCC1-positive expression was statistically significant in the older patients (P = 0.032). In the multivariate analysis, the prognostic factors for DFS were female sex (P = 0.016), N stage (P = 0.009), and postoperative carcinoembryonic antigen level (P = 0.001), but ERCC1 expression was not a statistically significant prognostic factor for DFS in the univariate analysis (P = 0.397). The 5-year DFS rate was not significantly associated with the ERCC1 expression in all patients (P = 0.396) or with stage III disease (P = 0.582). CONCLUSION: We found that ERCC1 expression was not significantly correlated with the 5-year DFS as reflected by the oncologic outcomes in patients with high-risk stages II and III colon cancer treated with FOLFOX adjuvant chemotherapy.

T4 stage and preoperative anemia as prognostic factors for the patients with colon cancer treated with adjuvant FOLFOX chemotherapy.

BACKGROUND: FOLFOX-based adjuvant chemotherapy is a benefit for high-risk stage II and stage III colon cancer after curative resection. But, the prognostic factor or predictive marker for the efficacy of FOLFOX remains unclear. This study was aimed to identify the prognostic value and cumulative impact of adjuvant FOLFOX on the stage II and III colon cancer patients. METHODS: A total of 196 stage II and III colon cancer patients were retrospectively enrolled in prospectively collected data. They underwent curative resection followed by FOLFOX4 adjuvant chemotherapy. The oncological outcomes included the 5-year disease-free survival (DFS) rate and 5-year overall survival (OS) rate. Cox-regression analysis was performed to identify the prognostic value, and its cumulative impact was analyzed. RESULTS: The 5-year DFS rate of the patients was 71.94% and the 5-year OS rate was 81.5%. The prognostic values for the 5-year DFS rate and 5-year OS rate were T4 stage and preoperative anemia in a multivariate analysis. Each patient group who had no prognostic value, single, or both factors revealed 95.35%, 69.06%, and 28.57% in the 5-year DFS rate, respectively (p < 0.0001). The 5-year OS rate also showed the significant differences in each group who had no prognostic value, single, or both factors revealed 100%, 79.3%, and 45.92%, respectively (p < 0.0001). CONCLUSION: Our results showed similar efficacy to MOSAIC study in stage II and stage III colon cancer patients treated with adjuvant FOLFOX chemotherapy after curative resection. Patients who had T4 stage and/or preoperative anemia showed worse prognosis than patients without any prognostic value. These findings suggest that FOLFOX could not be effective in the patients with T4 stage colon cancer accompanied by preoperative anemia.

Association Between Time (Initiation and Length) and Oncological Outcomes for the Patients with Colon Cancer Treated with Adjuvant Chemotherapy.

Adjuvant chemotherapy is benefit for high-risk stage II and stage III colon cancer after curative resection. But, the optimal time between surgical and initiation of adjuvant chemotherapy remains unclear. Moreover, no study of efficacy with different lengths of adjuvant chemotherapy has appeared. This study was aimed to identify association between time (initiation and length) and oncological outcomes of adjuvant chemotherapy on the stages II and III colon cancer patients. A total of 406 high-risk stages II and III colon cancer patients were retrospectively enrolled in prospectively collected data. They were categorized into three groups representing chemotherapy initiation time: less than 4 weeks (group 1), 4 to 6 weeks (group 2), and more than 6 weeks (group 3). They were categorized into two groups representing chemotherapy length time : less than 200 days (group 1a) and more than 200 days (group 2a). The 5-year disease-free survival (DFS) rates were 74.97 % in group 1, 76.94 % in group 2, and 63.97 % in group 3 (p > 0.05). The 5-year DFS rates were 75.49 % in the group that received adjuvant chemotherapy within 6 weeks and 63.97 % in the group that received adjuvant chemotherapy >6 weeks (p = 0.0539). The 5-year DFS rates were 77.21 % in group 1a and 81.82 % in group 2a (p > 0.05). Adjuvant chemotherapy should be safely offered within 6 weeks after surgical excision in patients with colon cancer after considering the patient's general physical condition and hematological factors, even if the chemotherapy length is prolonged.

Prognostic significance of the decreased rate of perioperative serum carcinoembryonic antigen level in the patients with colon cancer after a curative resection.

PURPOSE: The serum level of carcinoembryonic antigen (CEA) is a clinical prognostic factor in the follow-up evaluation of patients with colon cancer. We aimed to evaluate the prognostic significance of the rate of decrease of the perioperative serum CEA level in patients with colon cancer after a curative resection. METHODS: A total of 605 patients who underwent a curative resection for colon cancer between January 2000 and December 2007 were enrolled retrospectively. The rate of decrease was calculated using the following equation: ([preoperative CEA - postoperative CEA]/[preoperative CEA] ×100). RESULTS: In the group with a preoperative serum CEA level of >5 ng/mL, the normalized group with a postoperative serum CEA level of ≤5 ng/mL showed a better overall survival (OS) rate and disease-free survival (DFS) rate than those of the non-normalized group (P ≤ 0.0001). The "cutoff values" of the rate of decrease in the perioperative serum CEA that determined the OS and the DFS were 48.9% and 50.8%, respectively. In the multivariate analysis of preoperative serum CEA levels >5 ng/mL, the prognostic factors for the OS and the DFS were the cutoff value (P < 0.0001) and the pN stage (P < 0.0001). CONCLUSION: A rate of decrease of more than 50% in the perioperative serum CEA level, as well as the normalization of the postoperative serum CEA level, may be useful factors for determining a prognosis for colon cancer patients with high preoperative CEA levels.

All the commercially available adhesion barriers have the same effect on adhesion prophylaxis?; A comparison of barrier agents using a newly developed, severe intra-abdominal adhesion model.

BACKGROUND: Various types of adhesion barriers are widely used to prevent intra-abdominal adhesion. However, few studies have compared the efficacy of adhesion barriers using the same animal model. The aim of this study was to compare the anti-adhesive effects of various barrier agents using a newly developed, severe adhesion model. METHODS: A severe adhesion model was established by excision of a 1-cm(2) intra-abdominal wall and application of cyanoacrylate in rat. Eighty male Sprague-Dawley rats (10 weeks old; 370 ± 50 g) were divided randomly into four groups (n = 20 each): the untreated control group, G-group using a hyaluronic acid and sodium carboxymethyl cellulose gel (Guardix-sol®), A-group using 4% icodextrin (Adept®), and S-group using a hyaluronate-carboxymethyl cellulose membrane (Seprafilm®). The effect of each adhesion barrier was evaluated by means of the extent and severity of adhesion, difficulty of adhesiolysis scoring systems, and microscopic grade of fibrosis. RESULTS: The G-group showed no difference in adhesion score and fibrosis, the A-group demonstrated only a significantly lower fibrosis, and the S-group exhibited a significantly lower adhesion score and lower fibrosis compared with the control group. The S-group had a significantly lower adhesion score and reduced fibrosis compared with the G-group; however, no significant difference in adhesion score and fibrosis was noted with the A-group. CONCLUSIONS: The membranous barrier Seprafilm® may be effective in the prevention of adhesion in the condition of peritoneal injury combined with foreign material. Adept® showed a tendency of decreasing the severity of adhesion and was effective in the prevention of fibrosis.

Association between a close distal resection margin and recurrence after a sphincter-saving resection for t3 mid- or low-rectal cancer without radiotherapy.

PURPOSE: To maintain the patient's quality of life, surgeons strive to preserve the sphincter during rectal cancer surgery. This study evaluated the oncologic safety of a sphincter-saving resection with a distal resection margin (DRM) <1 cm without radiotherapy in T3, mid- or low-rectal cancer. METHODS: This retrospective study enrolled 327 patients who underwent a sphincter-saving resection for proven T3 rectal cancer located <10 cm from the anal verge and without radiotherapy between January 1995 and December 2011. The oncologic outcomes included the 5-year cancer-specific survival, the local recurrence, and the systemic recurrence rates. RESULTS: In groups A (DRM ≤1 cm) and B (DRM >1 cm), the 5-year cancer-specific survival rates were 81.57% and 80.03% (P = 0.8543), the 5-year local recurrence rates were 6.69% and 9.52% (P = 0.3981), and the 5-year systemic recurrence rates were 19.46% and 23.11% (P = 0.5750), respectively. CONCLUSION: This study showed that the close DRM itself should not be a contraindication for a sphincter-saving resection for T3 mid- or low-rectal cancer without radiotherapy. However, a prospective randomized controlled trial including the effect of adjuvant therapy will be needed.

Association of MUC6-minisatellite variants with susceptibility to rectal carcinoma.

A secreted MUC6 mucin is reported to be expressed highly in the stomach and gall bladder. In previous our study, the five minisatellites were identified and a significant association between MUC6-MS5 alleles and gastric cancer was reported. Because of aberrant MUC6 expression is often found in gastrointestinal diseases, we evaluated a relationship between MUC6-MS5 and susceptibility to colorectal cancers. Case-control study was performed with 1,103 cancer-free controls and 414 rectal cancer cases. A significant association (OR = 2.70) between short rare MUC6-MS5 alleles (7, 9 repeats) and the occurrence of cancer was observed in rectal cancer [95 % confidence interval (CI), 1.12-6.54; p = 0.022]. Furthermore, a comparison by gender showed the differences in the association ratios between rectal cancer and short rare MUC6-MS5 alleles: male, 3.97 (CI: 1.36-11.5; p = 0.006) versus female 0.91 (CI: 0.18-4.75; p = 0.913). We also examined the association according to lymphovascular invasion (LVI). The frequency of LVI positive rectal cancer was increased in short rare allele cases than in the total rectal cases: 16.2 % versus 42.9 %. Therefore, we suggest that the short rare MUC6-MS5 alleles may be related to cancer development in male and these cancer cases may be related the bad prognosis.

Adipose-tissue-derived Stem Cells Enhance the Healing of Ischemic Colonic Anastomoses: An Experimental Study in Rats.

PURPOSE: This experimental study verified the effect of adipose-tissue-derived stem cells (ASCs) on the healing of ischemic colonic anastomoses in rats. METHODS: ASCs were isolated from the subcutaneous fat tissue of rats and identified as mesenchymal stem cells by identification of different potentials. An animal model of colonic ischemic anastomosis was induced by modifying Nagahata's method. Sixty male Sprague-Dawley rats (10-week-old, 370 ± 50 g) were divided into two groups (n = 30 each): a control group in which the anastomosis was sutured in a single layer with 6-0 polypropylene without any treatment and an ASCtreated group (ASC group) in which the anastomosis was sutured as in the control group, but then ASCs were locally transplanted into the bowel wall around the anastomosis. The rats were sacrificed on postoperative day 7. Healing of the anastomoses was assessed by measuring loss of body weight, wound infection, anastomotic leakage, mortality, adhesion formation, ileus, anastomotic stricture, anastomotic bursting pressure, histopathological features, and microvascular density. RESULTS: No differences in wound infection, anastomotic leakage, or mortality between the two groups were observed. The ASC group had significantly more favorable anastomotic healing, including less body weight lost, less ileus, and fewer ulcers and strictures, than the control group. ASCs augmented bursting pressure and collagen deposition. The histopathological features were significantly more favorable in the ASC group, and microvascular density was significantly higher than it was in the control group. CONCLUSION: Locally-transplanted ASCs enhanced healing of ischemic colonic anastomoses by increasing angiogenesis. ASCs could be a novel strategy for accelerating healing of colonic ischemic risk anastomoses.

Adipose-derived stem cells on the healing of ischemic colitis: a therapeutic effect by angiogenesis.

BACKGROUND: There has been no specific treatment for ischemic colitis. We verified the effects of adipose-derived stem cells (ASCs) on ischemia-induced colitis in a rat model. METHODS: Forty male Sprague-Dawley rats (10 weeks old; weight, 350 ± 20 g) were divided into two groups: a control group (only fibrinogen and thrombin injected, n = 20) and an ASC group (local implantation of ASCs mixed with thrombin and fibrinogen, n = 20). An ischemic colitis model was established by modifying Nagahata's methods with double-blind randomization. ASCs (1 × 10(6) cells) were implanted intramurally into the ischemic area using a fibrin glue mixture. The severity of adhesion, degree of ileus, the number and size of the ulcers, Wallace macroscopic and microscopic scores, and microvascular density were measured. RESULTS: The degree of ileus was significantly lower, and significantly fewer and smaller ulcerations were found in the ASC group than those in the control group. Wallace macroscopic and microscopic scores were lower in the ASC group than in the control group (1.90 ± 1.22 versus 3.25 ± 1.83, p < 0.01 and 1.55 ± 1.88 versus 2.84 ± 1.89, p < 0.05, respectively). Microvascular density was higher in the ASC group than in the control (54.45 ± 19.45 versus 26.54 ± 13.14, p < 0.01, respectively). CONCLUSIONS: Local implantation of ASCs into an ischemic-injured colonic wall reduced the grade of ischemic injury and enhanced tissue healing by promoting angiogenesis.

Oncologic Outcomes and Risk Factors for Recurrence after Tumor-specific Mesorectal Excision of Rectal Cancer: 782 Cases.

PURPOSE: The aim of this study was to analyze the oncologic outcomes and the risk factors for recurrence after a tumor-specific mesorectal excision (TSME) of resectable rectal cancer in a single institution. METHODS: A total of 782 patients who underwent a TSME for resectable rectal cancer between February 1995 and December 2005 were enrolled retrospectively. Oncologic outcomes included 5-year cancer-specific survival and its affecting factors, as well as risk factors for local and systemic recurrence. RESULTS: The 5-year cancer-specific survival rate was 77.53% with a mean follow-up period of 61 ± 31 months. The overall local and systemic recurrence rates were 9.2% and 21.1%, respectively. The risk factors for local recurrence were pN stage (P = 0.015), positive distal resection margin, and positive circumferential resection margin (P < 0.001). The risk factors for systemic recurrence were pN stage (P < 0.001) and preoperative carcinoembryonic antigen level (P = 0.005). The prognostic factors for cancer-specific survival were pT stage (P < 0.001), pN stage (P < 0.001), positive distal resection margin (P = 0.005), and positive circumferential resection margin (P = 0.016). CONCLUSION: The oncologic outcomes in our institution after a TSME for patients with resectable rectal cancer were similar to those reported in other recent studies, and we established the risk factors that could be crucial for the planning of treatment and follow-up.

Prognostic Significance of Lymph Node Ratio in Stage III Rectal Cancer.

PURPOSE: Although nodal metastasis is the most powerful prognostic factor in rectal cancer, marked heterogeneity exists within stage III rectal cancer. Recent studies of rectal cancer have shown a prognostic superiority of the lymph node ratio (LNR) compared with N stage. The purpose of this study was to investigate the prognostic value of the LNR in the era of the 7th edition of the TNM classification. METHODS: We included 190 patients who underwent a curative resection for rectal cancer with nodal metastasis. The patients were divided into four groups on the basis of statistically calculated cut-off values as 0.21, 0.32, and 0.61. RESULTS: The LNR was an independent risk factor for overall survival (OS; P = 0.008) and for systemic recurrence-free survival (SRFS; P = 0.002). However, the LNR was not a predictive factor for local recurrence. When the N stage of the sixth TNM staging system was separately analyzed as a covariate, the LNR was also found to be a predictive factor for both OS and SRFS (P = 0.012 and P = 0.004, respectively). A LNR value of 0.21 offered the best cut off to separate patients into two prognostic groups. CONCLUSION: The defined cut-off values of the LNR were an independent risk factor for OS and distant metastasis-free survival in patients with rectal cancer, irrespective of the sixth or the seventh version of the TNM classification, and the LNR should be considered as a prognostic variable in any future staging system.

Massive small bowel bleeding caused by scrub typhus in Korea.

A 79-year-old man was diagnosed with scrub typhus based on fever, eschar, skin rash and a markedly elevated serum tsutsugamushi antibody and doxycycline was started. Five days later, hematochezia developed and multiple small bowel ulcerations with hemorrhage were seen on colonoscopy. Despite intensive therapy, the massive hematochezia worsened and the distal small bowel was resected. Multiple ulcerated lesions were identified pathologically as vasculitis caused by scrub typhus. This is the first reported case of pathologically proven small bowel involvement in scrub typhus infection.

A human monoclonal antibody scFv to urokinase plasminogen activator.

A human monoclonal antibody can be a good method for tumor diagnosis and treatment. This study is aimed at the generation of human antibody fragments against urokinase plasminogen activator (uPA) known to be related to tumor metastasis using the naive human antibody phage display library. Three clones--A2, A8, and E4--were selected from 1 x 10(10) sized human naïve antibody phage library using BIAcore rescue and screen. Clone A8 was finally selected by flow cytometry against Hep3 and HT1080, uPA overexpressing tumor cell lines. A8 clone consisted of 324 bp lambda and 402 bp heavy chains. The affinity (K(D)) of purified A8 antibody fragments was 1.44 x 10(-8) M(-1). The antibody fragment was reacted with HT1080 in a dose-dependent manner but not reacted with LS513 normal fibroblast. In this study, uPA specific human monoclonal antibody fragment A8 was made with BIAcore selection. Selected A8 was bound specifically to uPA expressed on the tumor cell surface. Further study for the application of A8 antibody clones will be needed.

Peripheral blood gene expression of B7 and CD28 family members associated with tumor progression and microscopic lymphovascular invasion in colon cancer patients.

PURPOSE: To associate the global gene expression of B7/CD28 family transcripts with pathologic features of colon cancer, we determined the B7/CD28 family transcripts in peripheral blood mononuclear cells (PBMCs) from normal subjects and patients with adenomatous polyps and colon cancer, and correlated the results with pathologic features of colon cancer. METHODS: PBMCs from age-matched normal subjects and patients with adenomatous polyps and colon cancer were analyzed for peripheral blood transcripts (PBTs) of B7/CD28 family using real-time PCR. Differences in expression levels of B7/CD28 PBTs across all cancer stages and between colon cancer patients with or without microscopic lymphovascular invasion (LVI) were analyzed. RESULTS: The results showed a significant upregulation of PBTs of co-inhibitory molecules such as B7-H3 and PD-1 and a significant PBT downregulation of co-stimulatory molecules including CD28 and ICOS in colon cancer patients. Furthermore, the increase of B7-H3 PBT was strongly associated with tumor invasion (P = 0.025) and advanced TNM stages (P = 0.019), whereas the decline of co-stimulatory ligand B7-H2 PBT was related to regional lymph node metastasis (P = 0.028) and aggressive tumor invasion (P = 0.031). In addition, the ratios of PBT expression of CD28 family to B7 family such as CTLA-4 to B7-H2 and PD-1 to B7-H2 were significantly higher in colon cancer patients with microscopic LVI than in those without LVI (P = 0.001 and P = 0.016, respectively). CONCLUSIONS: Our results suggest that B7/CD28 family PBTs may serve as valuable markers reflecting the pathological features of colon cancer.

Cyanoacrylate for colonic anastomosis; is it safe?

BACKGROUND: This experimental study evaluated the effectiveness and safety of using cyanoacrylate adhesive for sutureless colonic anastomosis and as a protective seal to prevent leakage. METHODS: Sixty male Sprague-Dawley rats (300 +/- 10 g, 9 weeks old) were divided into three groups: in group I, the anastomosis was sutured in a single layer with 5-0 polypropylene; in group II, the anastomosis was fixed using N-butyl-2-cyanoacrylate (Histoacryl(R)); and in group III, the anastomosis was sutured and then sealed with N-butyl-2-cyanoacrylate. The rats were sacrificed on postoperative day 7. The anastomoses among the three groups were compared by measuring wound infection, anastomotic leakage, anastomotic stricture, adhesion formation, anastomotic bursting pressure, and histological appearance. RESULTS: No anastomotic leakage was observed in any group. Anastomotic stricture was significantly more extensive in groups II and III (p < 0.001). Bursting pressure was significantly lower in groups II and III (168 +/- 58, 45 +/- 21, and 60 +/- 38 mmHg for groups I to III, respectively, p < 0.001). The severity of inflammatory reactions was significantly greater and collagen deposition was significantly lower in groups II and III (p < 0.05). CONCLUSIONS: N-butyl-2-cyanoacrylate could be a useful method for sutureless colonic anastomosis based on the absence of anastomotic leakage, but it may impede healing of the colonic anastomosis. In addition, when used to seal sutured colonic anastomoses, cyanoacrylate may have a negative influence on anastomotic healing. The clinical use of N-butyl-2-cyanoacrylate in colonic anastomosis does not appear to be acceptable and safer anastomotic methods or alternative forms of cyanoacrylate should be developed.