胆囊切除与结直肠息肉相关性的研究

背景：胆囊切除已被认为是结直肠癌的危险因素之一,但胆囊切除与结直肠息肉的关系一直未受到重视。目的：探讨胆囊切除与结直肠息肉的相关性。方法：连续收集经结肠镜排除恶性肿瘤、炎症性肠病、家族性腺瘤性息肉病等疾病的患者425例,根据既往有无胆囊切除史分为胆囊切除组（n=63）和对照组（n=362）,对两组患者结直肠息肉的发生率、内镜下息肉表现和组织学类型进行分析。结果：胆囊切除组结直肠息肉发生率高于对照组（46.0%对37.8%）,但差异无统计学意义（P=0.219）。两组患者息肉的部位和形态均无明显差异（P=0.753,P=0.127）;但胆囊切除患者腺瘤性息肉的发生危险显著高于对照组（OR=1.79,P=0.006）。亚组分析示胆囊切除史≥10年的结直肠息肉发生率与胆囊切除史〈10年无明显差异（P=0.11）。结论：胆囊切除并未增加结直肠息肉发生的危险性,但腺瘤性息肉的发生率显著增高,因此对胆囊切除患者应重视早期结直肠癌和腺瘤性息肉的筛查。     

Cholecystectomy and the Risk of Colorectal Adenomas

Cholecystectomy has been identified as a risk factor for colorectal cancer, yet little attention has been given to the relationship between cholecystectomy and colorectal adenomas. Utilizing data collected in two large cross-sectional studies of colorectal adenoma risk factors, we examined the association between cholecystectomy and colorectal adenomas. In the adjusted logistic regression model, both men and women showed no effect of cholecystectomy on risk of colorectal adenomas (men: OR 0.67 [95% CI 0.30–1.47]; women: OR 1.46 [95% CI 0.92–2.29]). No effect was seen when examining the time since cholecystectomy for men. There was a slight association found for women who had a cholecystectomy less than 10 years prior (OR 2.02 [95% CI 1.06–3.87]) but no association was seen in women with cholecystectomy at least 10 years prior (OR 1.14 [95% CI 0.62–2.09]). Thus, we conclude that, although cholecystectomy is a risk factor for colorectal cancer, cholecystectomy is not a risk factor for colorectal adenomas.     

胆囊切除与大肠癌

大肠癌是常见的恶性肿瘤之一，国外对大肠癌与胆囊病关系的研究已达到分子生物学水平。在国内虽然大肠癌发病率相对较低，但随着饮食结构的改变，大肠癌的发病率也逐年升高。但大肠癌的病因尚未明确，可能与饮食习惯、遗传素质、大肠腺瘤病、慢性黏膜炎症等有关。1978首次报道胆囊切除术可增加大肠癌的发病率，引起人们对两者之间关系的关注。     

Gallstones, Cholecystectomy, and Colorectal Cancer

Purpose : To examine the controversial association of gallstones, cholecystectomy and colorectal cancer. Methodologic explanations for the association include ascertainment bias, unequal diagnostic testing, and necropsy selection bias. Necropsy screening, which eliminates unequal diagnostic testing and ascertainment bias and reduces necropsy selection bias, was used to study this controversy. Methods : Adult necropsies at the University of Kansas Medical Center from 1950 to 1984 were reviewed. Patients with colorectal cancer, gallstones, or who had cholecystectomy during life were excluded. The remaining patients were those in whom neither colorectal cancer nor gallstones were suspected during life (reducing selection bias). The occurrence of gallstones and colorectal cancer among these individuals was then determined (reducing ascertainment bias and unequal diagnostic testing). Results : Of 7485 persons receiving necropsy, 239 had colorectal cancer diagnosed during life and an additional 604 had gallstones or cholecystectomy, leaving 6642 patients available for study. Overall, no association between colorectal cancer and gallstones was found. In women, gallstones were associated with colorectal cancer: 6/447 (1.3%) with gallstones had colorectal cancer compared with 11/2259 (0.4%) without gallstones who had colorectal cancer, p= 0.048, odds ratio 2.78 (95% CI 0.84–8.25). A stronger association was found between right-sided colorectal cancer and gallstones (odds ratio 6.79, 95% CI 1.14-46,46). Conclusions :These data suggest an association between gallstones and colorectal cancer among women. Gallstones may indicate patients at higher risk for colorectal cancer. Studies associating cholecystectomy with colorectal cancer may be explained—not by ascertainment bias—but, rather, by susceptibility bias. The reason for the cholecystectomy (gallstones) may be the correct association and not the cholecysteetomy itself.     

microRNA与结直肠癌关系的研究进展

结直肠癌的发病是一个多因素、多步骤的演进过程,基因表达异常在其中起重要作用.近年研究发现多种microRNA（miRNA）在结直肠癌中表达异常,可能参与了肿瘤的发生、发展过程,有望成为结直肠癌早期诊断、临床分期、个体化治疗、靶向治疗和预后评估的分子标记物.本文就近年来有关miRNA与结直肠癌天系的研究进展作一综述.     

Early-Age-at-Onset Colorectal Cancer and Microsatellite Instability as Markers of Hereditary Nonpolyposis Colorectal Cancer

PURPOSE: Early-age-at-onset colorectal cancer and microsatellite instability are characteristic features of hereditary nonpolyposis colorectal cancer. Our aim was therefore to investigate whether these features might be useful markers in screening for hereditary nonpolyposis colorectal cancer and mismatch repair gene mutations. METHODS: From 1,132 consecutive patients who underwent surgery for colorectal cancer at our department between 1980 and 1999, we selected all patients 40 years of age or younger (study group, n = 59) and a subset of patients 40 years of age or older (control group, n = 60) who were matched for gender and pathologic TNM stage. Patients for whom a complete family cancer history or microsatellite status was unavailable were excluded from the study. Family cancer histories, retrieved from archival charts, were reassessed. Microsatellite status was investigated with the five microsatellites from the Bethesda recommended panel (BAT-26, BAT-25, D2S123, D5S346, and D17S250). On the basis of the number of altered microsatellites ( 2, 1, or 0), tumors were considered as having high or low instability or microsatellite stability, respectively. Mutation analysis for MLH1 and MSH2 genes was performed only in cases of high instability. DNA was investigated for mutations by single-strand conformational polymorphism and sequencing analysis. RESULTS: Data from 95 patients (study group: n = 37, 18 males, mean age 35 years; control group: n = 58, 29 males, mean age 62 years) were available for analysis. Four patients (study group, n = 3; control group, n = 1) fulfilled the Amsterdam II criteria for hereditary nonpolyposis colorectal cancer. Of the 37 study group tumors, 12 (32.4 percent) showed high-frequency microsatellite instability, and 25 had microsatellite stability, whereas among the 58 control group tumors, 4 (7 percent) showed high-frequency microsatellite instability, and 54 had microsatellite stability (P < 0.002). Mismatch repair gene mutation analysis was performed in 12 cases (study group, n = 7; control group, n = 5). We found four mutations (MSH2 119delG, MLH1 ex9 684insT, MSH2 Gln239Stop, and MLH1 del0.8 Kb) in the study group patients and none in the control group. Of four hereditary nonpolyposis colorectal cancer patients who underwent mismatch repair gene mutation analysis, one had a mutation. CONCLUSIONS: Early-age-at-onset colorectal cancer is significantly correlated with high-frequency microsatellite instability tumor status and is a useful criterion to identify hereditary nonpolyposis colorectal cancer patients. Moreover, when used in association with high-frequency microsatellite instability status, it is effective in selecting patients for mismatch repair gene mutation analysis.     

Colorectal Cancer Mortality in First-Degree Relatives of Early-Onset Colorectal Cancer Cases

PURPOSE: Estimates of familial colorectal cancer risks are useful in genetic counseling and as a guide to determining entry into screening programs and trials of chemoprevention. Furthermore, they provide an insight into the contribution of the known colorectal cancer genes to the familial risk of the disease. There is a paucity of data about the familial colorectal cancer risk associated with early-onset disease outside the recognized cancer predisposition syndromes. METHODS: This was a retrospective cohort study. The parents and siblings of 205 patients with colorectal cancer aged less than 55 years at diagnosis were studied for mortality and cancer incidence. RESULTS: The overall standardized mortality ratio of colorectal cancer compared with the Northern Irish population was 3.54 (95 percent confidence interval, 2.59–4.79). There was some evidence that a family history of colorectal cancer is associated with a greater risk of colon (4.16; 95 percent confidence interval, 2.83–5.91) rather than rectal cancer (2.62; 95 percent confidence interval, 1.43–4.40). Risks in parents (2.54; 95 percent confidence interval, 1.45–3.72) were lower than in siblings (6.15; 95 percent confidence interval, 3.90–9.23). CONCLUSION: First-degree relatives of patients with early-onset disease are at a marked increase in risk. There is evidence that risks vary depending on the type of affected relative and by the site of colorectal cancer. This information should be considered in formulating screening strategies.     

吸烟与结直肠癌发病关系的研究进展

结直肠癌的发病是一个多因素参与、多阶段演进的过程,不良生活方式可能是散发性结直肠癌的重要病因之一。尽管多数流行病学研究表明吸烟可增加结直肠癌的风险,但仍存在争议。本文对关于吸烟与结直肠癌发病关系的主要队列研究和病例对照研究,以及吸烟致结直肠癌的可能机制,包括免疫抑制、炎症相关结直肠癌、结肠传输时间延迟、微卫星不稳定和高甲基化、癌基因和抑癌基因以及代谢酶基因多态性作一综述。     

Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome): Criteria for Identification and Management

Hereditary nonpolyposis colorectal carcinoma (HNPCC), or Lynch syndrome, is an autosomal dominant syndrome accounting for 5 to 10% of the total colorectal cancer population. Patients with this syndrome develop colorectal carcinoma at an early age, but disease onset can happen in all age groups. Usually the carcinomas are synchronous or metachronous, and most of them arise proximal to the splenic flexure. The prognosis is better than for the sporadic form of cancer, and there is increased risk for cancer development in certain extracolonic sites, such as the endometrium, ovary, stomach, small bowel, hepatobiliary tract, ureter, and renal pelvis. Most patients with HNPCC have a mutation in one of two DNA mismatch repair genes, hMSH2 or hMLH1. More than 90% of colorectal carcinoma patients with hMSH2 or hMLH1 demonstrate high-frequency microsatellite instability (MSI-H). If a patient is suspected to belong to an HNPCC family, the first screening test should be immunohistochemistry for the detection of hMLH1 and hMSH2 proteins, and if it is indicative, it should be followed by genomic sequencing for the identification of mutations in the mismatch repair genes. Genetic counseling and surveillance for high risk HNPCC family members should begin at age 25. Surveillance includes annual colonoscopy of the entire large bowel, with fecal occult blood testing performed twice a year. Systematic surveillance and individually designed treatment of affected patients may help to detect cancers at an earlier stage and subsequently improve the prognosis of the disease further.     

Increased Risk of Cancer after Cholecystectomy: A Nationwide Cohort Study in Korea including 123,295 Patients

Background/AimsContradictory findings on the association between cholecystectomy and cancer have been reported. We aimed to investigate the risk of all types of cancers or site-specific cancers in patients who underwent cholecystectomy using a nationwide dataset.MethodsSubjects who underwent cholecystectomy from January 1, 2007, to December 31, 2014, who were older than 20 years and who underwent an initial baseline health check-up within 2 years were enrolled. Those who were diagnosed with any type of cancer before the enrollment or within 1 year after enrollment were excluded. Ultimately, patients (n=123,295) who underwent cholecystectomy and age/sex matched population (n=123,295) were identified from the database of the Korean National Health Insurance Service. The hazard ratio (HR) and 95% confidence interval (CI) for cancer were estimated, and Cox regression analysis was performed.ResultsThe incidence of cancer in the cholecystectomy group was 9.56 per 1,000 person-years and that in the control group was 7.95 per 1,000 person-years. Patients who underwent cholecystectomy showed an increased risk of total cancer (adjusted HR, 1.19; 95% CI, 1.15 to 1.24; p<0.001), particularly leukemia and malignancies of the colon, liver, pancreas, biliary tract, thyroid, pharynx, and oral cavity. In the subgroup analysis according to sex, the risk of developing cancers in the pancreas, biliary tract, thyroid, lungs and stomach was higher in men than in women.ConclusionsPhysicians should pay more attention to the possibility of the occurrence of secondary cancers among patients who undergo cholecystectomy.     

Extracolonic Findings at Virtual Colonoscopy: An Important Consideration in Asymptomatic Colorectal Cancer Screening

Background  Virtual colonoscopy has been evaluated for use as a colorectal cancer screening tool, and in prior studies, it has been estimated that the evaluation of extra-colonic findings adds $28-$34 per patient studied. Methods  As an ancillary study to a prospective cohort study comparing virtual colonoscopy to conventional colonoscopy for colorectal cancer detection, the investigators retrospectively determined the number and estimated costs of all clinic visits, imaging and laboratory studies, and medical procedures that were generated as a direct result of extra-colonic findings at virtual colonoscopy. Results  We enrolled 143 subjects who underwent CTC followed by conventional colonoscopy. Data were available for 136 subjects, and 134 (98%) had at least one extra-colonic finding on CT. Evaluation of extra-colonic findings was performed in 32 subjects (24%). These subjects underwent 73 imaging studies, 30 laboratory studies, 44 clinic visits, 6 medical procedures, and 44 new or return outpatient visits over a mean of 38 months following the CTC. The most common findings causing further evaluation were lung nodules and indeterminate kidney lesions. No extra-colonic malignancies were found in this study. A total of $33,690 was spent in evaluating extra-colonic findings, which is $248 per patient enrolled. Conclusions  The cost of the evaluation of extra-colonic findings following virtual colonoscopy may be much higher in actual practice than is suggested by prior studies. This will impact the cost-effectiveness of using virtual colonoscopy for asymptomatic colorectal cancer screening and underscores the importance of standardizing the reporting of extra-colonic findings to encourage appropriate follow-up. Presented at the American College of Gastroenterology Annual Meeting, October 2006.     

Braf基因突变检测方法及其与结直肠癌关系的研究进展

丝裂原活化蛋白激酶（MAPK）通路异常激活在人类多种肿瘤的发生、发展中起重要作用，Braf基因突变是其中的重要环节。该突变的检测方法主要有限制性片段长度多态性（RFIJP）、单链构象多态性（SSCP）、实时荧光聚合酶链反应（PCR）、变性高效液相色谱分析（DHPLC）、基因芯片、直接测序等。遗传性非息肉性结直肠癌（HNPCC）患者不存在Braf基因突变，而结直肠锯齿状病变中该突变较多见。以Braf基因突变为治疗靶点或作为入选标准选取患者．并采用特定药物治疗在结直肠癌的治疗中具有良好的应用前景。     

Minnesota Colorectal Cancer Initiative: Successful Development and Implementation of a Community-Based Colorectal Cancer Registry

PURPOSE The aim of the Minnesota Colorectal Cancer Initiative is to implement risk-specific interventions to decrease colorectal cancer morbidity and mortality by 1) assisting clinicians to identify and educate individuals and families at high and increased risk for colorectal cancer; 2) providing professional and community education; 3) maintaining a database to evaluate the effectiveness of preventive intervention strategies; and 4) facilitating colorectal cancer research.METHODS Two physician groups and the University Cancer Center founded the Minnesota Colorectal Cancer Initiative as a not-for-profit organization. Health care organizations, pharmaceutical companies, a consulting firm, and other practice groups provide continuing financial and other support. A database registry, risk-assessment survey, and consent document were developed and then were approved by an institutional review board. A trial enrollment was conducted. Minnesota Colorectal Cancer Initiative services are available to the public. Participants are actively recruited through member organizations. Minnesota Colorectal Cancer Initiative assesses hereditary risk and will document family history in the medical record on request. A personally targeted reply letter reviews risk factors and recommends specific screening and surveillance strategies for participants and their family members, and when appropriate, provides information regarding genetic counseling and testing services. Minnesota Colorectal Cancer Initiative services are free to participants.RESULTS Since 1999, Minnesota Colorectal Cancer Initiative has sent individually tailored reply letters providing risk-specific information about colorectal cancer to 717 participants and more than 3200 of their first-degree and second-degree relatives. More than 200 families, previously unidentified as having histories suggestive of hereditary colorectal cancer (attenuated familial polyposis and hereditary nonpolyposis colorectal cancer), have been identified; genetic services were explained and recommended. A formal program evaluation confirmed that Minnesota Colorectal Cancer Initiative provides useful information and materials and promotes intrafamilial communication about colon cancer risk and recommendations.CONCLUSIONS Minnesota Colorectal Cancer Initiative is a model of effective collaboration between academic and community health care providers. A community-based registry is a unique way to identify and provide personal, risk-specific information to large numbers of people at increased or high risk for colorectal cancer.Poster presentation at the meeting of the American Society of Colon and Rectal Surgeons, June 21 to 26, 2003, New Orleans, Louisiana.     

Outcome of Metastatic Colorectal Cancer: Analysis of a Consecutive Series of 229 Patients. The Impact of a Multidisciplinary Approach

Purpose New chemotherapy agents and integrated treatments have improved the prognosis of patients with metastatic colorectal cancer. Methods From January 2000 to December 2002, 229 consecutive metastatic patients were prospectively followed and their outcomes were analyzed. They were divided initially into four treatment groups: A, palliative chemotherapy for extensive extrahepatic disease with or without hepatic disease (97 patients); B, palliative chemotherapy as in Group A for extensive hepatic disease unlikely to become resectable (36 patients); C, neoadjuvant chemotherapy for potentially resectable liver metastases if responsive to therapy (33 patients); D, immediate surgery for liver metastases (63 patients). Results The series was analyzed after a median follow-up of 22.6 months. The median progression-free survival was 9, 7.3, 11.5, and 26 months in Groups A, B, C, and D, respectively. The median overall survival was 20.1, 17.2, 24.8, and >48 months in Groups A, B, C, and D, respectively. The outcome was considered for the 69 patients with metastases confined to the liver (Groups B and C), who were treated initially with chemotherapy. Surgery was performed in 21 patients (5 from Group B, and 16 from Group C) and was R0 in 16. In resected patients, the median progression-free survival was 14.7 months and the median overall survival was 40.5 months. In unresected patients, the median progression-free survival was 7.6 months and the median overall survival was 17.5 months. Conclusions Neoadjuvant therapy may prolong overall survival in a subset of patients with multiple hepatic metastases. The global impact on progression-free survival is low; less than one-half of the patients resected after chemotherapy are disease-free at three years. However, patients resected after chemotherapy obtained overall survival similar to that of primary surgery, suggesting a positive role for integrated approaches. Supported by grants from Associazione per la Ricerca e la Cura sul Cancro (AIRC, Milano, Italy), Consiglio Nazionale della Ricerche (CNR, Progetto Strategico Oncologia), and Ministero dell’Istruzione, dell’Università e della Ricerca (MIUR, Ricerca Finalizzata 2001, sottoprogetto B55.4.2). Reprints are not available.     

Chemoprevention of Colorectal Cancer

Colorectal cancer is a major public health concern in all developed countries. Despite decades of advances in the treatment and prevention of colorectal cancer, it remains the second most common cause of cancer death. However, the optimal method for early detection remains unknown and patient compliance with screening recommendations remains poor. This has led to the development of complementary strategies, such as chemoprevention to reduce morbidity and mortality from colorectal cancer. Chemoprevention is defined as the use of specific pharmacologic or nutrient agents to prevent, reverse, or inhibit the process of carcinogenesis. This review was designed to discuss the most promising agents in colorectal chemoprevention. Supported by grants from the NIH K07 CA092445, The Cancer Research Prevention Foundation, and The Eleanor Naylor Dana Charitable Trust. Presented at the Colorectal Disease Symposium, Ft. Lauderdale, Florida, February 12 to 14, 2005.     

Differences between right- and left-sided colon cancer in patient characteristics, cancer morphology and histology

Background and Aim: Recently, the clinical and biological differences between right‐ and left‐sided colon cancers have been widely debated. However, close analyses of these clinical differences, based on large‐scale studies, have been scarcely reported. Methods: A total of 3552 consecutive Japanese colorectal cancer cases were examined and the clinical differences between right‐ and left‐sided colon cancer cases were investigated. Results: The proportion of right‐sided colon cancer was relatively high in patients aged less than 40 years (33%) and more than 80 years (43%). The proportion of right‐sided colon cancer in patients aged 40–59 years was relatively low (male 22% and female 29%). In male patients the proportion increased in the 70‐79 years age group (30%), while in female patients the proportion increased in the 60‐69 years age group (39%). Right‐sided colon cancer was more likely to be detected at an advanced stage (T1 stage; left 22%, right 15%) (P < 0.01) with severe symptoms. Polypoid‐type early cancer was dominant in the left colon (left 59%; right 40%) (P < 0.01), while the proportion of flat‐type early cancer in the right colon was significantly higher than that in the left colon (left 25%; right 44%) (P < 0.01). Conclusions: Specific age distribution of right‐sided colon cancer was observed and the difference between male and female patients was highlighted. Other clinical features also differed between right‐ and left‐sided colon cancer, suggesting that different mechanisms may be at work during right and left colon carcinogenesis.     

Polypectomy of Adenomas in the Prevention of Colorectal Cancer: 10 Years' Follow-up of the Telemark Polyp Study I A Prospective,Controlled Population Study

Background: The efficacy of polypectomy in preventing colorectal cancer (CRC) has never been demonstrated in a controlled, prospective study. This must be done by randomization within a population with a high prevalence of colorectal polyps, and the feasibility and safety of endoscopic screening examination is a prerequisite for this type of study. Methods: The present study is a randomized, controlled study of the feasibility and safety of flexible sigmoidoscopic screening of a normal population sample of 799 men and women aged 50–59 years, findings at 2 and 6 years' colonoscopic follow-up, and the appearance of clinical colorectal cancer (CRC) after 10 years. Results: The attendance rate was high, and there were no complications. After 10 years 1 of 400 in the screening group had developed CRC (in the group of 76 (19%) not attending for screening examination). Four of 399 controls developed CRC. Conclusion: Poor yield of polyps at follow-up, slow growth of in situ polyps, and no clinical CRC among screenees after 10 years provides support to infrequent or no colonoscopic follow-up after initial polypectomy in individuals with otherwise average risk of CRC.     

A New Risk-Scoring System for Colorectal Cancer and Polyp Screening by Turkish Colorectal Cancer and Polyp Study Group

Background:Colorectal cancer is one of the most commonly diagnosed types of cancer worldwide. An early diagnosis and detection of colon cancer and polyp can reduce mortality and morbidity from colorectal cancer. Even though there are a variety of options in screening tests, the question remains on which test is the most effective for the early detection of colorectal cancer. In this prospective study, we aimed to develop a simple, useful, effective, and reliable scoring system to detect colon polyp and colorectal cancer.Methods:We enrolled 6508 subjects over the age of 18 from 16 centers, with colonoscopy screening. The age, smoking status, alcohol consumption, body mass index, polyp incidence, polyp size, number and localization, and pathologic findings were recorded.Results:The age, male gender, obesity, smoking, and family history were found as independent risk factors for adenomatous polyp. We have developed a new scoring system which can be used for these factors. With a score of 4 or above, we found the following: sensitivity 81%, specificity 40%, positive predictive value 25.68%, and negative predictive value 89.84%, for adenomatous polyp detection; and sensitivity 96%, specificity 39%, positive predictive value 3.35%, negative predictive value 99.29%, for colorectal cancer detection.Conclusion:Even though the first colorectal cancer screening worldwide is generally performed for individuals over 50 years of age, we recommend that screening for colorectal cancer might begin for those under 50 years of age as well. Individuals with a score ≥ 4 must be included in the screening tests for colorectal cancer.