结肠癌合并肠梗阻手术治疗112例

目的探讨结肠癌合并肠梗阻的诊断和最佳手术治疗方案。方法对1995年11月～2007年11月我们收治的112例结肠癌合并肠梗阻手术治疗的临床资料进行回顾性分析。结果 112例结肠癌合并肠梗阻中,慢性不全梗阻有89例(79.5%),急性完全性肠梗阻23例(20.5%)。112例均行手术探查,其中98例一期切除吻合术,9例切除后肠造瘘二期吻合术,5例一期近端造瘘二期切除吻合术;一期手术切除率95.5%,术后并发症12例(10.7%),死亡2例(1.8%)。结论结肠癌合并肠梗阻绝大多数为慢性不全肠梗阻。结肠癌是急性完全性结肠梗阻的主要原因。早期诊断早期手术治疗是挽救病人生命的关键。结肠切除术是解除结肠癌合并肠梗阻的主要手术方式,理想的手术方式是Ⅰ期根治切除吻合术,有效的结肠灌洗可提高工期根治切除手术率。

左半结肠癌致急性肠梗阻手术治疗38例

目的 探讨左半结肠癌致急性肠梗阻手术治疗方法。方法 38例患者其中 3例直肠上段癌采用Hartmann’s手术 ,其余均采用肿瘤切除术、Ⅰ期肠吻合术。结果 所有患者均痊愈出院 ,行Hartmann ,s手术者 2例分别于术后 2 .5年及 3年再次入院行肠切除术。结论 左半肠癌肠梗阻患者足可以应用肿瘤切除术、Ⅰ期肠吻合术。

老年结直肠癌并急性肠梗阻28例

目的探讨老年结直肠癌合并急性肠梗阻的外科处理原则和方法。方法回顾分析28例老年结直肠癌合并急性肠梗阻的临床资料,右半结肠癌12例,左半结肠癌14例,直肠癌2例。行右半结肠癌一期切除吻合12例,左半结肠癌一期切除吻合14例。Hartmann术l例,Dixon术1例。结果术后出现并发症,切口感染3例,切口裂开2例,肺部感染1例。结论老年人结直肠癌合并急性肠梗阻一期切除吻合是方便、安全、有效的治疗方法。

Role of probiotics,prebiotics and synbiotics in chemoprevention for colorectal cancer

Colorectal cancer is the third most common form of cancer.Current treatments are all associated with a high risk of complications and a low success rate.Recently,synbiotics have been proposed as a new preventive and therapeutic option.There is no direct experimental evidence for cancer suppression in humans as a result of the consumption of pro-,pre-or synbiotics.However,there is a wealth of evidence emerging from laboratory studies.The mechanisms by which pro-,pre-and synbiotics may inhibit colon cancer are now beginning to be understood and will be addressed in the present review.

Risk for colorectal cancer in ulcerative colitis:Changes,causes and management strategies

The risk of colorectal cancer for any patient with ulcer-ative colitis is known to be elevated, and is estimated to be 2% after 10 years, 8% after 20 years and 18% after 30 years of disease. Risk factors for cancer in-clude extent and duration of ulcerative colitis, primary sclerosing cholangitis, a family history of sporadic colorectal cancer, severity of histologic bowel inflam-mation, and in some studies, young age at onset of colitis. In this review, the authors discuss recent epide-miological trends and causes for the observed chang-es. Population-based studies published within the past 5 years suggest that this risk has decreased over time, despite the low frequency of colectomies. The crude annual incidence rate of colorectal cancer in ulcerative colitis ranges from approximately 0.06% to 0.16% with a relative risk of 1.0-2.75. The exact mechanism for this change is unknown; it may partly be explained by the more widespread use of maintenance therapy and surveillance colonoscopy.

Specific CEA-producing colorectal carcinoma cell killing with recombinant adenoviral vector containing cytosine deaminase gene

AIM: To kill CEA positive colorectal carcinoma cells specifically using the E coli cytosine deaminase (CD) suicide gene, a new replication-deficient recombinant adenoviral vector was constructed in which CD gene was controlled under CEA promoter and its in vitro cytotoxic effects were evaluated. METHODS: Shuttle plasmid containing CD gene and regulatory sequence of the CEA gene was constructed and recombined with the right arm of adenovirus genome DNA in 293 cell strain. Dot blotting and PCR were used to identify positive plaques. The purification of adenovirus was performed with ultra-concentration in CsCl step gradients and the titration was measured with plaque formation assay. Cytotoxic effects were assayed with MTT method, The fifty percent inhibition concentration (IC(50)) of 5-FC was calculated using a curve-fitting parameter. The human colorectal carcinoma cell line, which was CEA-producing, and the CEA-nonproducing Hela cell line were applied in cytological tests. An established recombinant adenovirus vector AdCMVCD, in which the CD gene was controlled under CMV promoter, was used as virus control. Quantitative results were expressed as the mean +/- SD of the mean. Statistical analysis was performed using ANOVA test. RESULTS: The desired recombinant adenovirus vector was named AdCEACD. The results of dot blotting and PCR showed that the recombinant adenovirus contained CEA promoter and CD gene. Virus titer was about 5.0 X 10(14)pfu/L(-1) after purification. The CEA-producing Lovo cells were sensitive to 5-FC and had the same cytotoxic effect after infection with AdCEACD and AdCMVCD (The IC(50) values of 5-FC in parent Lovo cells, Lovo cells infected with 100 M.O.I AdCEACD and Lovo cells infected with 10 M.O.I AdCMVCD were 】15000, 216.5+/-38.1 and 128.8+/-25.4 micromol.L(-1), P【0.001, respectively), and the cytotoxicity of 5-FC increased accordingly when the m.o.i of adenoviruses were enhanced (The value of IC(50) of 5-FC was reduced to 27.9+/-4.2 micromol.L(-1) in 1000 M.O.I AdCEACD infected Lovo cells and 24.8+/-7.1 micromol.L(-1) in 100 M.O.I AdCMVCD infected Lovo cells, P【0.05, P【0.01, respectively). The CEA-nonproducing Hela cells had no effect after infection with AdCEACD, but Hela cells had the cytotoxic sensitivity to 5-FC after infection with AdCMVCD (The IC(50) of 5-FC in parent Hele cells and Hela cells infected with AdCMVCD at 10 M.O.I was 】15000 and 214.5+/-31.3 micromol.L(-1), P【0.001). AdCEACD/5-FC system also had bystander effect, and the viability was about 30 percent when the proportion of transfected cells was only 10 percent. CONCLUSION: The recombinant adenovirus vector AdCEACD has the character of cell type-specific gene delivery. The AdCEACD/5-FC system may become a new, potent and specific approach for the gene therapy of CEA-positive neoplasms, especially colon carcinoma.

Identification of specific genes and pathways involved in NSAIDs-induced apoptosis of human colon cancer cells

AIM: To study whether indomethacin (IND), a nonselective cyclooxygenase (COX) inhibitor or NS-398 (NS), a COX-2-selective inhibitor, induces apoptosis in human colon cancer cells and which apoptosis-related genes and pathways are involved. METHODS: Human colon cancer Caco-2 cells were treated with either: placebo, IND (0.05-0.5 mmol/L) or NS (0.01-0.2 mmol/L) for 1, 5 and 18 h. We then studied: (1) Cell death by the TUNEL method, (2) mRNA expression of 96 apoptosis-related genes using DNA microarray, (3) expression of selected apoptosis related proteins by Western blotting. RESULTS: Both IND and NS induced apoptosis in 30%-50% of Caco-2 cells in a dose dependent manner. IND (0.1 mmol/L for 1 h) significantly up-regulated pro-apoptotic genes in four families: (1) TNF receptor and ligand, (2) Caspase, (3) Bcl-2 and (4) Caspase recruiting domain. NS treatment up-regulated similar pro-apoptotic genes as IND. In addition, IND also down-regulated anti-apoptotic genes of the IAP family. CONCLUSION: (1) Both non-selective and COX-2-selective NSAIDs induce apoptosis in colon cancer cells in a dose dependent manner. (2) Both NSAIDs induce apoptosis by activating two main apoptotic pathways: the death receptor pathway (involving TNF-R) and the mitochondrial pathway. (3) IND induces apoptosis by up-regulating pro-apoptotic genes and down-regulating anti-apoptotic genes, while NS only up-regulates pro-apoptotic genes. (4) Induction of apoptosis in coloncancer cells by NSAIDs may explain in part, their inhibitory action on colon cancer growth.

Prognostic factors of young patients with colon cancer after surgery

AIM： To investigate the prognostic factors of 96 young patients with colon cancer within a cancer center by univariate and multivariate analysis. METHODS： A total of 723 patients with colon cancer were treated surgically during a period of 10 years. Ninty six of them were 40 years old or younger. R0, R1 and R2 operations were performed in 69 （71.9%）, 4 （4.1%） and 23 patients （24%）, respectively. Left hemicolectomy was performed in 43 patients, right hemicolectomy in 37 patients, transverse colon resection in 9 patients and low anterior resection in 7 patients. Cox multivariate regression analysis was performed to identify predictors of survival. RESULTS： The operation mortality was 0%, 54 patients died within 111 mo after operation due to occurrence or metastases of the tumor. Liver, lung and bone metastases occurred in 3, 1 and 5 patients, respectively. The mean survival time for all patients was 77.9 ± 5.01 mo and the overall 3-, 5- and 10- year survival rates were 66.68%, 58.14% and 46.54%, respectively. In the univariate survival analysis, patient age, type of operation, radical resection, blood transfusion, histological type, diameter of tumor, depth of tumor invasion, lymphatic invasion, distant metastases, liver metastases and TNM stage were found to be predictors of survival in young patients with colon cancer. In the Cox-regression analysis, blood transfusion and lymphatic invasion were determined as independent prognostic factors of survival. CONCLUSIONS： Age, type of operation, radical resection, blood transfusion, histological type, diameter of tumor, depth of tumor invasion, lymphatic invasion, distant metastasis and TNM stage are the predictors of survival in young patients with colon cancer after surgery.

Effects of endostatin on expression of vascular endothelial growth factor and its receptors and neovascularization in colonic carcinoma implanted in nude mice

AIM:To investigate the antiangiogenic effects of endostatin on colonic carcinoma cell line implanted in nude mice and its mechanism. METHODS:Nude mice underwent subcutaneous injection with LS-174t colonic carcinoma cell line to generate carcinoma and were randomly separated into two groups.Mice received injection of vehicle or endostatin every day for two weeks. After the tumor was harvested,the tumor volumes were determined,and the expressions of CD34,VEGF and FIk-1 were examined by immunohistochemical method. RESULTS:Tumor volume was significantly inhibited in the endostatin group(84.17%)and tumor weight was significantly inhibited in the endostatin group(0.197±0.049) compared to the control group(1.198±0.105)(F=22.56, P=0.001),microvessel density(MVD)was significantly decreased in the treated group(31.857±3.515)compared to the control group(100.143±4.290)(F=151.62,P<0.001). Furthermore,the expression of FIk-1 was significantly inhibited in the treated group(34.29%) ompared to the control group(8.57%)(X^2=13.745,P=0.001).However no significant decrease was observed in the expression of vascular endothelial growth factor(VEGF)between these two groups(X^2=0.119,P=0.730). CONCLUSION:Endostatin can inhibit tumor growth and angiogenesis by blocking Vegf/FIk-1 pathway.This experiment provides the theory basis for developing a new anti-carcinoma drug through studying the properties of anti-angiogenesis inhibitors.

Bevacizumab plus infusional 5-fluorouracil,leucovorin and irinotecan for advanced colorectal cancer that progressed after oxaliplatin and irinotecan chemotherapy:A pilot study

AIM： To evaluate the combination of bevacizumab with infusional 5-fluorouracil （5-FU）, leucovorin （LV） and irinotecan （FOLFIRI） in patients with advanced colorectal cancer （CRC） pretreated with combination regimens including irinotecan and oxaliplatin. METHODS： Fourteen patients （median age 56 years） with advanced CRC, all having progressed after oxaliplatin- and irinotecan-based combination chemotherapy, were enrolled in this study. Patients were treated with 2 h infusion of irinotecan 150 mg/m2 on d 1, plus bevacizumab 5 mg/kg iv infusion for 90 min on d 2, and iv injection of LV 20 mg/m2 followed by a bolus of 5-FU 400 mg/m2 and then 22 h continuous infusion of 600 mg/m2 given on two consecutive days every 14 d. RESULTS： The median number of cycles of chemotherapy was six （range 3-12）. The response rate was 28.5%, one patient had a complete response, and three patients had a partial response. Eight patients had stable disease. The median time to progression was 3.9 mo （95% CI 2.0-8.7）, and the median overall survival was 10.9 mo （95% CI 9.6-12.1）. Grade 3/4 neutropenia occurred in five patients, and two of these developed neutropenic fever. Grade 3 hematuria and hematochezia occurred in one. Grade 2 proteinuria occurred in two patients. However, hypertension, bowel perforation or thromboembolic events did not occur in a total of 90 cycles. CONCLUSION： Bevacizumab with FOLFIRI is well tolerated and a feasible treatment in patients with heavily treated advanced CRC.

Obesity and colorectal cancer risk: A meta-analysis of cohort studies

TO evaluate the association between obesity and colorectal cancer risk. METHODS： We searched PubMed, EMBASE, and the Cochrane Library up to January 1, 2007. Cohort studies permitting the assessment of causal association between obesity and colorectal cancer, with clear definition of obesity and well-defined outcome of colorectal cancer were eligible. Study design, sample size at baseline, mean follow-up time, co-activators and study results were extracted. Pooled standardized effect sizes were calculated.

Irinotecan therapy and molecular targets in colorectal cancer: A systemic review

Irinotecan is the second line chemotherapy for advanced stage colorectal cancer (CRC) after failure of first line chemotherapy with oxaliplatin and 5-fluorouracil. The aim of this review is to analyse the data on irinotecan as second line chemotherapy for advanced CRC and the potential roles of the molecular markers, p53 and vascular endothelial growth factor (VEGF) in the management of advanced CRC. Thus, the English literature from 1980 to 2008 concerning irinotecan, p53, VEGF and CRC was reviewed. On review, Phase and clinical trials showed thatirinotecan improves pain-free survival, quality of life, 1-year survival, progression-free survival and overall survival in advanced CRC. p53 and VEGF were expressed in CRC and had a predictive power of aggressive clinical behaviour in CRC. Irinotecan sensitizes p53 wild type, mutant and null cells to Fasmediated cell apoptosis in CRC cells. Wild type p53 cells were more sensitive to irinotecan than mutated p53. Irinotecan has an anti-VEGF effect inhibiting endothelial cell proliferation, increasing apoptosis and reducing microvascular density which is onlylimited by irinotecan toxicity levels. To conclude, irinotecan improves the patient's quality of life and the survival rates of patients with advanced CRC. p53 and VEGF status of the patients' tumour is likely to affect the responsiveness of CRC to irinotecan. It is recommended that studies of the expression of these molecular markers in relation to chemoresponsiveness ofirinotecan should be carried out for better management of patients with advanced CRC.

Pharmacogenomics in colorectal cancer: The first step for individualized-therapy

Interindividual differences in the toxicity and response to anticancer therapies are currently observed in practically all available treatment regimens. A goal of cancer therapy is to predict patient response and toxicity to drugs in order to facilitate the individualization of patient treatment. Identification of subgroups of patients that differ in their prognosis and response to treatment could help to identify the best available drug therapy according the genetic profile. Several mechanisms have been suggested to contribute to chemo-therapeutic drug resistance: amplification or overexpression of membrane transporters, changes in cellular proteins involved in detoxification or in DNA repair, apoptosis and activation of oncogenes or tumor suppressor genes. Colorectal cancer (CRC) is regarded as intrinsically resistant to chemotherapy. Several molecular markers predictive of CRC therapy have been included during the last decade but their results in different studies complicate their application in practical clinical. The simultaneous testing of multiple markers predictive of response could help to identify more accurately the true role of these polymorphisms in CRC therapy. This review analyzes the role of genetic variants in genes involved in the action mechanisms of the drugs used at present in colorectal cancer.

Identification of Lynch syndrome: How should we proceed in the 21^(st) century?

Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC), is the most common form of hereditary colorectal cancer. Although great advances in the understanding of its molecular basis have taken place in the last decade, optimal selection of individuals for HNPCC genetic testing remains controversial. This is especially relevant since colonoscopy has been proven effective for reducing colorectal cancer incidence and mortality in individuals at-risk for this disorder. In this manuscript, we summarize the most significant contributions to this important issue that have appearedin the last few years.

Influence of Perioperative Blood Transfusion on Prognosis in Patients with Colon Cancer

Objective： To explore the influence of perioperative blood transfusion on the postoperative survival of patients with colon cancer. Methods： Univariate and multivariate retrospective analyses were performed on the survival in a total of 723 colon cancer patients which were treated surgically during a period of 10 years. Results： Kaplan-Meier estimates showed that more than 800 mL perioperative blood transfusion was the survival predictor. Blood transfusion influenced significantly the prognosis of patients 40 years old and younger, those undergoing helicoloectomy left side, those with papillary adenocarcinoma, those with big tumors （diameter ≥ 8 cm）, those with stage Ⅰ tumors, those with lymphatic node metastases and those without liver metastases. In multivariate analysis only the tumor location, radicality of operation, lymphatic invasion, liver metastasis, depth of tumor invasion and TNM stage retained their significance. Conclusion： Perioperative blood transfusion is some extent. The indication of blood transfusion the prognostic factor for patients with colon cancer to must be restricted strictly, specially in patients younger than 40 years old, with right side lesion, papillary adenocarcinoma, big tumors （diameter ≥8 cm）, stage Ⅰ tumors and lymphatic node metastases or without liver metastases. But perioperative blood transfusion may not be deleterious for patients with staging Ⅳ disease and with distant metastases.

Effect of oral Lactococcus lactis containing endostatin on 1, 2-dimethylhydrazine-induced colon tumor in rats

AIM： To investigate the effects of oral Lactococcus lactis （L lactis） containing endostatin on 1, 2-dimethylhydrazine （DMH）-induced rat colorectal cancer. METHODS： Recombinant endostatin was produced by the expression of L lactis NZ9000. Sixty male Wistar rats were injected with DMH （40 mg/kg body weight） subcutaneously once a week for 10 wk to induce colorectal cancer. The rats were gavaged with 1 mL of endostatin at a dose of 1×10^8/d and fed with the basal diet. The animals were killed after 22 wk for histopathological examination. The total time of experimental observation was 58 wk. RESULTS： Rat endostatin protein was expressed in L lactis. Recombinant endostatin exhibited a significant effect on colorectal cancer （P〈0.05）. Furthermore, the mean survival time of the rats treated with endostatin was longer than that of the animals treated with DMH. There was no statistically significant difference between the rats treated with endostatin and those treated with DMH. The results showed that endostatin could not result in complete cure. CONCLUSION： Oral endostatin exerts an influence on the progression of chemically induced colon tumors.

Bacteria,inflammation,and colon cancer

Our relationship with the colonic bacterial flora has long been viewed as benign, but recent studies suggest that this symbiosis has risks as well as benefits. This relationship requires that the host not only provide a supportive environment for the symbiotic bacteria, but also actively maintain intact mechanisms for properly managing the physiologic stresses that are closely associated with the symbiont’s essential survival functions. Failure to do so breaches the host- symbiont contract, and can result in serious effects on the health of the host. Recent investigations that employ several knockout mouse models reveal the consequences of genetic deficiency in the host regarding these mechanisms, and the latent, pro-inflammatory, tumorigenic nature of normal bacterial flora. Further study of the interactions between normal bacterial flora and hosts could shed light on the etiologies and pathogenesis of inflammatory diseases and related cancers, with implications for human health.

Evolution in the treatment of metastatic colorectal carcinoma of the liver

Metastatic colorectal cancer to the liver is associated with a uniform poor prognosis without treatment. Advances in therapy over the past decades have now allowed surgical resections of the liver to occur with a low morbidity and mortality. Improvements in chemotherapy regimes have paralleled technical improvements and now allow a new group of patients to become eligible for surgical resection. This chapter will review the recent advances in surgical and chemotherapeutic regimes in metastatic colorectal cancer to the liver.

Exploiting novel molecular targets in gastrointestinal cancers

Novel molecular targets are being discovered as we learn more about the aberrant processes underlying various cancers. Efforts to translate this knowledge are starting to impact on the care of patients with gastrointestinal cancers. The epidermal growth factor receptor (EGFR) pathway and angiogenesis have been targeted successfully in colorectal cancer with cetuximab, panitunumab and bevacizumab. Similarly, EGFR-targeting with erlotinib yielded significant survival benefit in pancreatic cancer when combined with gemcitabine. The multi-targeting approach with sorafenib has made it the first agent to achieve significant survival benefit in hepatocellular carcinoma. Efforts to exploit the dysregulated Akt/mTOR pathway in GI cancer therapy are ongoing. These molecular targets can be disrupted by various approaches, including the use of monoclonal antibody to intercept extracellular ligands and disrupt receptor-ligand binding, and small molecule inhibitors that interrupt the activation of intracellular kinases.

Contrast-enhanced intraoperative ultrasonography equipped with late Kupffer-phase image obtained by sonazoid in patients with colorectal liver metastases

AIM: To find occult metastases during hepatectomy in patients with colorectal cancer liver metastases (CRCLM), contrast-enhanced intraoperative ultrasonography (CE-IOUS) was performed using a new microbubble agent, sonazoid, which provides a parenchyma-specific contrast image based on its accumulation in the Kupffer cells. METHODS: Eight patients with CRCLM underwent CE- IOUS using sonazoid before hepatectomy. The liver was investigated during a late Kupffer-phase imaging, which is a valuable characteristic of sonazoid. RESULTS: CE-IOUS using sonazoid provided the early vascular- and sinusoidal-phase images for 10 min followed by the late Kupffer-phase image up to 30 min after the injection of sonazoid. IOUS did not provide new findings of metastatic lesion in the 8 patients. However, during the late Kupffer-phase image of sonazoid, a metastatic lesion was newly found in two of the 8 patients. These newly detected lesions were removed by an additional hepatectomy and histopathologically diagnosed as a metastasis. CONCLUSION: CE-IOUS using sonazoid can allow surgeons to investigate the whole liver with enough time and to find new metastases intraoperatively.