内源性肿瘤坏死因子与结直肠癌关系的探讨

用ＥＬＩＳＡ法测定２４例结、直肠癌患者血浆、外周血单个核细胞（ＰＢＭＣ）、癌组织ＴＮＦ水平，与良性病变，正常人对照。结果：（１）结、直肠癌组血浆ＴＮＦ水平显著升高，ＤｕｄｅｓＤ期患者血浆ＴＮＦ水平显著高于ＤｕｄｅｓＢ或Ｃ期；ＰＢＭＣ经ＬＰＳ诱生的ＴＮＦ民对照组比较无显著性差异；（２）结、直肠癌组织ＴＮＦ水平显著高于正常（Ｐ〈０．０１），肿瘤最大直径在５．０ｃｍ以上者，癌组织ＴＮＦ清单或高；（３）肿     

Dietary glycemic load and colorectal cancer risk

Background:Insulin and insulin-like growth factors can stimulateproliferation of colorectal cells. High intake of refined carbohydrates andmarkers of insulin resistance are associated with colorectal cancer. To testthe insulin/colon cancer hypothesis, we determined whether the dietaryglycemic index and the glycemic load are associated with colorectal cancerrisk. Design:A case-control study on colorectal cancer conducted inItaly. Cases included 1125 men and 828 women with histologically confirmedincident cancer of the colon or rectum. Controls were 2073 men and 2081 womenhospitalized for acute conditions. We calculated average daily dietaryglycemic index and glycemic load, and fiber intake from a validated foodfrequency questionnaire. Results:Direct associations with colorectal cancer risk emergedfor glycemic index (odds ratio (OR) in highest vs. lowest quintile = 1.7;95% confidence interval (CI): 1.4–2.0) and glycemic load (OR =1.8; 95% CI: 1.5–2.2), after allowance for sociodemographicfactors, physical activity, number of daily meals, and intakes of fiber,alcohol and energy. ORs were more elevated for cancer of the colon thanrectum. Overweight and low intake of fiber from vegetables and fruit appearedto amplify the adverse consequences of high glycemic load. Conclusions:The positive associations of glycemic index and loadwith colorectal cancer suggest a detrimental role of refined carbohydrates inthe etiology of the disease.     

LINE-1 hypomethylation is inversely associated with microsatellite instability and CpG island methylator phenotype in colorectal cancer

Two pathways leading to vulvar squamous cell carcinoma (SCC) exist. The expression of proliferation- and cell-cycle-related biomarkers and the presence of high-risk (hr) HPV might be helpful to distinguish the premalignancies in both pathways. Seventy-five differentiated vulvar intra-epithelial neoplasia (VIN)-lesions with adjacent SCC and 45 usual VIN-lesions (32 solitary and 13 with adjacent SCC) were selected, and tested for hr-HPV DNA, using a broad-spectrum HPV detection/genotyping assay (SPF(10)-LiPA), and the immunohistochemical expression of MIB1, p16(INK4A) and p53. All differentiated VIN-lesions were hr-HPV- and p16-negative and in 96% MIB1-expression was confined to the parabasal layers. Eighty-four percent exhibited high p53 labeling indices, sometimes with parabasal extension. Eighty percent of all usual VIN-lesions were hr-HPV-positive, p16-positive, MIB1-positive and p53-negative. Five (of seven) HPV-negative usual VIN lesions, had an expression pattern like the other HPV-positive usual VIN lesions. In conclusion, both pathways leading to vulvar SCC have their own immunohistochemical profile, which can be used to distinguish the 2 types of VIN, but cannot explain differences in malignant potential.     

腹腔镜下结直肠癌手术--80例的初步体会

目的探讨腹腔镜结直肠癌手术的安全性、有效性及手术适应证.方法回顾分析2001年12月～2004年5月间共80例结直肠癌患者施行腹腔镜下手术的经验.结果全组中直肠癌30例,肛管癌1例,共施行Dixon手术11例,Miles手术20例;结肠癌49例,施行乙状结肠癌切除术6例,右半结肠切除术41例,横结肠和左半结肠切除术各1例.中转开腹率20%,术中并发症发生率3.8%,术后并发症发生率3.75%,无吻合口漏,无手术死亡病例,平均清扫淋巴结12.5枚,平均随访12.6个月.结论只要严格掌握适应证,选择适合病人,结直肠腹腔镜手术是安全、有效的.     

Meta-analysis of 16 studies of the association of alcohol with colorectal cancer

Alcohol consumption is an established risk factor for colorectal cancer (CRC). However, while studies have consistently reported elevated risk of CRC among heavy drinkers, associations at moderate levels of alcohol consumption are less clear. We conducted a combined analysis of 16 studies of CRC to examine the shape of the alcohol–CRC association, investigate potential effect modifiers of the association, and examine differential effects of alcohol consumption by cancer anatomic site and stage. We collected information on alcohol consumption for 14,276 CRC cases and 15,802 controls from 5 case-control and 11 nested case-control studies of CRC. We compared adjusted logistic regression models with linear and restricted cubic splines to select a model that best fit the association between alcohol consumption and CRC. Study-specific results were pooled using fixed-effects meta-analysis. Compared to non-/occasional drinking (≤1 g/day), light/moderate drinking (up to 2 drinks/day) was associated with a decreased risk of CRC (odds ratio [OR]: 0.92, 95% confidence interval [CI]: 0.88–0.98, p = 0.005), heavy drinking (2–3 drinks/day) was not significantly associated with CRC risk (OR: 1.11, 95% CI: 0.99–1.24, p = 0.08) and very heavy drinking (more than 3 drinks/day) was associated with a significant increased risk (OR: 1.25, 95% CI: 1.11–1.40, p < 0.001). We observed no evidence of interactions with lifestyle risk factors or of differences by cancer site or stage. These results provide further evidence that there is a J-shaped association between alcohol consumption and CRC risk. This overall pattern was not significantly modified by other CRC risk factors and there was no effect heterogeneity by tumor site or stage.     

Alcohol and colorectal cancer: a case-control study from northern Italy

The role of alcohol consumption in the etiology of colorectal cancer has been investigated in a case-control study conducted from 1985 to 1990 in the northern part of Italy, on 889 cases of colon cancer, 581 cases of rectal cancer, and 2,475 controls admitted to hospital for acute, non-neoplastic, nodigestive disordes. After allowance for age, education, study center, body mass index, and approximate total energy intake, no significant associations between alcohol intake and the risk of cancer of the colon or rectum were found (odds ratios [OR] for 42 drinks/week cf none =1.0 (95 percent confidence interval [CI]=0.8–1.4) and 0.7 (CI=0.5–1.0) for cancer of the colon and rectum, respectively). A significant increase in the risk of colon cancer with increasing alcohol consumption was, however, observed in females (OR for 28 drinks/week cf none = 1.8 (CI=1.1–3.0)). While the results of the present case-control study do not suggest that alcohol plays a role in the etiology of colon or rectum cancer overall, they provide a hint for a weak association between alcohol consumption and colon cancer among females which, because of the similarities with breast cancer, should be evaluated in the context of the possible relationship between colon cancer, alcohol intake, and female hormones.Drs Barra, Franceschi, and Guarneri, are with the Epidemiology Unit, Aviano Cancer Center Aviano, Italy. Dr Franceschi is also with the European Cancer Prevention Organisation (ECP), Epidemiology and Cancer Working Group, Brussels, Belgium. Drs Negri and La Vecchia are with the Mario Negri Institute for Pharmacological Research, Milan, Italy. Dr La Vecchia is also with the Institute of Social and Preventive Medecine, University of Lausanne, Lausanne, Switzerland. Address correspondence to Dr Barra, Epidemiology Unit, Aviano Cancer Center, Via Pedemontana Occ., 33081 Aviano (PN) Italy. Support for this project was contributed by the Italian Association for Research on Cancer and the Italian League against Tumors, Milan and the Italian National Research Council (CNR Applied Project Clinical Applications of Oncological Research).     

The role of galectins in colorectal cancer progression

Galectins constitute a family of 15 mammalian galactoside-binding proteins that share a consensus amino acid sequence in their carbohydrate binding sites. They are multi-functional molecules and are expressed widely in human tissues. Four galectins: galectin -1, -3, -4 and -8 are expressed in the human colon and rectum and their expressions show significant changes during colorectal cancer development and metastasis. These changes in galectin expression correlate with alterations in cancer cell growth, apoptosis, cell-cell and cell-matrix interactions and angiogenesis. This review summaries current knowledge of the expression and roles of these galectins in the progression of human colorectal cancer and discusses the relevance of galectins and their ligands as potential therapeutic targets for cancer treatment.     

The role of the barium enema in the diagnosis of colorectal neoplasia

The recent interest in guidelines for colorectal cancer diagnosis, management and in screening has important implications for radiologists. The present article reviews the role of the barium enema in colorectal neoplasia diagnosis in symptomatic patients, and in the context of screening programmes.     

Intake of wholegrain products and risk of colorectal cancers in the Diet,Cancer and Health cohort study

Background:

Consumption of wholegrain (WG) products may protect against colon and rectal cancer.

Methods:

The associations between total and individual WG product consumption and colon and rectal cancer risk were prospectively examined using data on 461 incident cases of colon cancer and 283 incident cases of rectal cancer that developed during 10.6 years (median) of follow-up among 26 630 men and 29 189 women taking part in the Diet, Cancer and Health cohort. Incidence rate ratios (IRRs) of colon and rectal cancer related to total or individual WG product intake were calculated using Cox regression.

Results:

Higher WG product intake was associated with lower risk of colon cancer and rectal cancer in men. The adjusted IRR (95% CI) was 0.85 (0.77–0.94) for colon cancer and 0.90 (0.80–1.01) for rectal cancer per daily 50 g increment in intake. For colon cancer the association was confined to intake of WG bread in particular. No consistent associations between total or individual WG product consumption and colon or rectal cancer risk were observed in women.

Conclusion:

The findings suggest that higher total WG product intake is associated with a lower risk of colon and perhaps rectal cancer in men, but not in women.     

Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion versus systemic chemotherapy alone for colorectal peritoneal carcinomatosis

BACKGROUND:

Survival benefit of cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion was demonstrated by a prospective randomized trial for colorectal peritoneal carcinomatosis. Because of a recent substantial improvement in chemotherapy, the authors analyzed treatment options of colorectal carcinomatosis in the current era.

METHODS:

Consecutive patients with colorectal carcinomatosis treated by cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion from 2001 to 2007 were included. The control group patients with carcinomatosis received contemporary chemotherapy alone. Overall survival was the primary endpoint.

RESULTS:

All patients underwent systemic chemotherapy. The cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion group (n = 67) was similar to the control group (n = 38) in sex, tumor grade, site of tumor origin, T status, and N status. The control group was, however, older (59 vs 51 years; P<.001). Median survival measured from the diagnosis of peritoneal disease was longer with cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion (34.7 months vs 16.8 months; P<.001). Presence of liver metastasis was a significant negative predictor of survival (hazard ratio, 2.13).

CONCLUSIONS:

The authors concluded that 1) contemporary chemotherapy is associated with prolonged survival among patients with carcinomatosis as compared with historical controls, and 2) addition of cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion to modern chemotherapy regimens may significantly prolong survival. Cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion and systemic chemotherapy are not competitive therapies, and they both have a role in a multidisciplinary approach to patients with carcinomatosis. Cancer 2010. © 2010 American Cancer Society.     

Coffee drinking and colorectal cancer and its subsites: A pooled analysis of 8 cohort studies in Japan

Coffee is a rich source of bioactive compounds that have potential anticarcinogenic effects. However, it remains unclear whether coffee drinking is associated with colorectal cancer. Also, despite different etiological factors involved in gut physiology, few studies have investigated this association by anatomical site of the lesion. To address these issues, this study examined the association between coffee drinking and colorectal cancer in a pooled analysis from 8 cohort studies conducted in Japan. Among 320,322 participants followed up for 4,503,274 person‐years, 6,711 incident colorectal cancer cases were identified. Study‐specific hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models and then pooled using the random effects model. Coffee drinking was not materially associated with colorectal cancer risk in men or women (pooled HR 0.92, 95% CI 0.82–1.03 in men and pooled HR 0.90, 95% CI 0.76–1.07 in women). Analysis by subsite showed a lower risk of colon cancer among female drinkers of ≥3 cups coffee/day (pooled HR 0.80, 95% CI 0.64–0.99). There was no such association in men. Coffee drinking was not associated with risk of rectal cancer in men or women. Results were virtually the same among never smokers except for an increased risk of rectal cancer associated with frequent coffee consumption. Coffee drinking may be associated with lower risk of colon cancer in Japanese women.     

Ghrelin administration suppresses inflammation‐associated colorectal carcinogenesis in mice

Ghrelin is a 28-amino-acid peptide that stimulates the release of pituitary growth hormone. Because of its orexigenic effects, ghrelin is being developed as a therapeutic option for postoperative support and treatment of anorexia-cachexia syndrome of cancer patients. However, ghrelin has a multiplicity of physiological functions, and it also affects cell proliferation. Therefore, the effects of ghrelin administration on carcinogenesis and cancer progression in patients susceptible to cancer should be clarified. In this study, we examined the effects of ghrelin on cancer promotion in vivo using murine intestinal carcinogenesis models. Intestinal tumorigenesis was examined to determine the effects of either exogenous ghrelin administration or ghrelin deficiency following deletion of the Ghrl gene. Two murine intestinal tumorigenesis models were used. The first was the azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced inflammation-associated colon carcinogenesis model and the second was the Apc^Min/+ genetic cancer susceptibility model. In AOM/DSS-treated mice, administration of ghrelin significantly suppressed tumor formation in the colon. In contrast, ghrelin administration did not affect the number of intestinal tumors formed in Apc^Min/+ mice. The absence of endogenous ghrelin did not affect the incidence of intestinal tumors in either AOM/DSS-treated mice or Apc^Min/+ mice, though tumor size tended to be larger in Ghrl^−/− colons in the AOM/DSS model. No tumor-promoting effect was observed by ghrelin administration in either tumorigenesis model. In summary, this study provides in vivo experimental evidence for the usefulness of ghrelin administration in the chemoprevention of inflammation-associated colorectal carcinogenesis and may suggest its safety in patients under colitis-associated cancer susceptibility conditions.     

Body fatness at an early age and risk of colorectal cancer

While there is convincing evidence that excess body fatness in adulthood is positively associated with colorectal cancer risk, the association between body fatness at an early age (≤30 years) and the risk of colorectal cancer has been equivocal. The present meta‐analysis was performed to clarify this association. PubMed and Web of Science databases were searched for relevant studies that investigated this association. The risk estimates from each study were transformed into a continuous variable for each 5 kg/m² increase in body mass index (BMI). A random effects model was used to calculate the summary relative risks (RRs) with 95% confidence intervals (CIs). A total of 15 observational studies (13 cohort studies and two case‐control studies) were included in this meta‐analysis. Each 5 kg/m² increase in BMI was significantly associated with a 13% (RR 1.13, 95% CI 1.08, 1.19), 17% (RR 1.17, 95% CI 1.09, 1.25) and 8% (RR 1.08, 95% CI 1.04, 1.11) higher risk of colorectal cancer overall, in men, and in women, respectively. Substantial heterogeneity was observed across studies. Based on the anatomic subsite, each 5 kg/m² increase in BMI was significantly associated with a 14% (RR 1.14, 95% CI 1.07, 1.22) higher risk of colon cancer, whereas no association (RR 1.03, 95% CI 0.95, 1.13) was observed with rectal cancer. In summary, body fatness at an early age may affect colon cancer risk later in life. Prevention of overweight and obesity in young individuals should be emphasized to prevent early‐onset colon cancer attributed to excess body fatness.     

Tumor suppressive microRNA-137 negatively regulates Musashi-1 and colorectal cancer progression

Stem cell marker, Musashi-1 (MSI1) is over-expressed in many cancer types; however the molecular mechanisms involved in MSI1 over-expression are not well understood. We investigated the microRNA (miRNA) regulation of MSI1 and the implications this regulation plays in colorectal cancer. MicroRNA miR-137 was identified as a MSI1-targeting microRNA by immunoblotting and luciferase reporter assays. MSI1 protein was found to be highly expressed in 79% of primary rectal tumors (n=146), while miR-137 expression was decreased in 84% of the rectal tumor tissues (n=68) compared to paired normal mucosal samples. In addition to reduced MSI1 protein, exogenous expression of miR-137 inhibited cell growth, colony formation, and tumorsphere growth of colon cancer cells. Finally, in vivo studies demonstrated that induction of miR-137 can decrease growth of human colon cancer xenografts. Our results demonstrate that miR-137 acts as a tumor-suppressive miRNA in colorectal cancers and negatively regulates oncogenic MSI1.     

Genetic variation in bone morphogenetic protein and colon and rectal cancer

Bone morphogenetic proteins (BMP) are part of the TGF-β-signaling pathway; genetic variation in these genes may be involved in colorectal cancer. In this study, we evaluated the association between genetic variation in BMP1 (11 tagSNPs), BMP2 (5 tagSNPs), BMP4 (3 tagSNPs), BMPR1A (9 tagSNPs), BMPR1B (21 tagSNPs), BMPR2 (11 tagSNPs) and GDF10 (7 tagSNPs) with risk of colon and rectal cancer and tumor molecular phenotype. We used data from population-based case-control studies (colon cancer n = 1,574 cases, 1,970 controls; rectal cancer n = 791 cases, 999 controls). We observed that genetic variation in BMPR1A, BMPR1B, BMPR2, BMP2 and BMP4 was associated with risk of developing colon cancer, with 20 to 30% increased risk for most high-risk genotypes. A summary of high-risk genotypes showed over a twofold increase in colon cancer risk at the upper risk category (OR = 2.49 95% CI = 1.95, 3.18). BMPR2, BMPR1B, BMP2 and GDF10 were associated with rectal cancer. BMPR2 rs2228545 was associated with an almost twofold increased risk of rectal cancer. The risk associated with the highest category of the summary score for rectal cancer was 2.97 (95% CI = 1.87, 4.72). Genes in the BMP-signaling pathway were consistently associated with CIMP+ status in combination with both KRAS-mutated and MSI tumors. BMP genes interacted statistically significantly with other genes in the TGF-β-signaling pathway, including TGFβ1, TGFβR1, Smad 3, Smad 4 and Smad 7. Our data support a role for genetic variation in BMP-related genes in the etiology of colon and rectal cancer. One possible mechanism is via the TGF-β-signaling pathway.