胆汁酸与大肠癌相关性的荟萃分析

目的 为了阐明粪便中总胆汁酸和单一胆汁酸的浓度是否与大肠癌的发生有关,我们对目前所有相关文献进行了荟萃分析.方法 检索以下电子数据库:Pubmed、Embase、the Cochrane Controlled Trials Register、the Science Citation Index和中文科技期刊数据库.根据纳入标准,纳入有关评价粪便胆汁酸和大肠癌/腺瘤关系的观察性试验.文献必需报道了患者和对照组的粪便中总胆汁酸、鹅脱氧胆酸、脱氧胆酸或石胆酸的浓度.我们计算加权均数差(weighted mean difference,WMD)和95%可信区间(95%confidence interval,CI).通过漏斗图肉眼观察是否存在发表偏倚,并做Begg和Egger检验进一步验证.结果 我们检索到了20个病例对照研究或队列研究(共1226例).无论是固定效应模型,还是随机效应模型,对所有研究进行汇总后均未发现粪便中总胆汁酸和大肠癌/腺瘤存在联系(WMD0.61,95% CI 0.35～1.57)mg/g冻干粪).相比对照组,大肠癌/腺瘤巾鹅脱氧胆酸、脱氧胆酸和石胆酸的浓度显著增加,分别为WMD 0.16、0.40、0.32,95% CI 0.00～0.32,0.18～0.61,0.12～0.53 mg/g冻干粪.然而初级胆汁酸和次级胆汁酸浓度却并无差异.结论 粪便中总胆汁酸与大肠癌/腺瘤无关联,但鹅脱氧胆酸和石胆酸可能涉及大肠癌的发生,脱氧胆酸则可能同大肠癌和大肠腺瘤都存在联系.     

Prospective Study Comparing Multislice CT Colonography With Colonoscopy in the Detection of Colorectal Cancer and Polyps

PURPOSE: Multislice CT colonography is an alternative to colonoscopy. The purpose of this study was to compare multislice CT colonography with colonoscopy in the detection of colorectal polyps and cancers. METHODS: Between June 2000 and December 2001, 45 males and 35 females (median age, 68 (29–83) years) with symptoms of colorectal disease were studied prospectively. All patients underwent multislice CT colonography and colonoscopy, and the findings were compared. RESULTS: Colonoscopy was incomplete in 18 (22 percent) patients because of obstructing lesions or technical difficulty, and multislice CT colonography was unsuccessful in 4 (5 percent) because of fecal residue. Colonoscopy was normal in 26 patients and detected 29 colorectal cancers and 33 polyps in 35 patients, diverticulosis in 16 patients, and colitis in 3 patients. Multislice CT colonography identified 28 of 29 colorectal cancers with one false negative and one false positive (sensitivity, 97 percent; specificity, 98 percent; positive predictive value, 96 percent; negative predictive value, 98 percent). Multislice CT colonography identified all 12 polyps measuring 10 mm in diameter (sensitivity, 100 percent), 5 of 6 measuring 6 to 9 mm in diameter (sensitivity, 83 percent), 8 of 15 polyps 5 mm (sensitivity, 53 percent), and false-positive for 8 polyps. The overall sensitivity was 74 percent and specificity 96 percent. The positive predictive value for polyps was 88 percent, and the negative predictive value was 90 percent. Multislice CT colonography also detected 5 of 16 patients with diverticulosis (sensitivity, 31 percent; specificity, 98 percent) and colitis in 2 of 3 patients (sensitivity, 67 percent; specificity, 100 percent). In ten (13 percent) patients, extracolonic findings on multislice CT colonography altered management and included five patients with colorectal liver metastases. In 15 (19 percent) patients, there were incidental findings that did not demand further investigation. CONCLUSIONS: The results from this study indicate that the efficacy of multislice CT colonography in the detection of colorectal cancers and polyps 6 mm is similar to colonoscopy. Multislice CT colonography allows clinical staging of colorectal cancers, outlines the whole length of the colon in obstructing carcinoma when colonoscopy fails, and can identify extracolonic causes of abdominal symptoms.     

Follow-Up After Curative Resection of Colorectal Cancer: A Meta-Analysis

Purpose This is a systematic review to evaluate the impact of various follow-up intensities and strategies on the outcome of patients after curative surgery for colorectal cancer. Methods All randomized trials up to January 2007, comparing different follow-up intensities and strategies, were retrieved. Meta-analysis was performed by using the Forest plot review. Results Eight randomized, clinical trials with 2,923 patients with colorectal cancer undergoing curative resection were reviewed. There was a significant reduction in overall mortality in patients having intensive follow-up (intensive vs. less intensive follow-up: 21.8 vs. 25.7 percent; P = 0.01). Regular surveillance with serum carcinoembryonic antigen (P = 0.0002) and colonoscopy (P = 0.04) demonstrated a significant impact on overall mortality. However, cancer-related mortality did not show any significant difference. There was no significant difference in all-site recurrence and in local or distant metastasis. Detection of isolated local and hepatic recurrences was similar. Intensive follow-up detected asymptomatic recurrence more frequently (18.9 vs. 6.3 percent; P < 0.00001) and 5.91 months earlier than less intensive follow-up protocol; these were demonstrated with all investigation strategies used. Intensive surveillance program detected recurrences that were significantly more amenable to surgical reresection (10.7 vs. 5.7 percent; P = 0.0002). The chance of curative reresection were significantly better with more intensive follow-up (24.3 vs. 9.9 percent; P = 0.0001), independent of the investigation strategies used. Conclusions Intensive follow-up after curative resection of colorectal cancer improved overall survival and reresection rate for recurrent disease. However, the cancer-related mortality was not improved and the survival benefit was not related to earlier detection and treatment of recurrent disease. ^aDeceased. Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Seattle, Washington, June 3 to 7, 2006.     

Lymphatic Staging in Colorectal Cancer: Pathologic, Molecular, and Sentinel Node Techniques

PURPOSE Accurate staging in colorectal cancer is important to predict prognosis and identify patients who could benefit from adjuvant therapy. Patients with lymphatic metastasis, Stage III/Dukes C, are generally treated with adjuvant chemotherapy. Still, patients without lymphatic metastasis do have relapse as high as 27 percent in five years in Dukes B2. It is hypothesized that these patients have occult (micro)metastasis in their lymph nodes. If these (micro)metastasis can be identified, these patients might benefit from adjuvant therapy. We reviewed the literature on procedures to improve lymph node staging.METHODS An extensive literature search was performed in PubMed (www.pubmed.com). Using the reference lists, more articles were found.RESULTS We found 30 articles about sentinel node in colorectal cancer describing original series. Some groups reported several studies including the same patients. We reported their largest studies. For all other techniques, we only included key articles.CONCLUSIONS Many techniques to improve staging have been described. The finding of occult (micro)metastasis is of prognostic significance in most studies. The sentinel node technique has been recently described for use in colorectal cancer. Although it seems clear that this technique has prognostic potential, it is not yet been shown in a follow-up study. Furthermore, the finding of occult (micro)metastasis in any technique used has not been shown to be clinically significant. Whether to treat patients with adjuvant therapy if occult (micro)metastasis are found needs to be proven in future studies.     

Screening Colonoscopy for Colorectal Cancer in Asymptomatic People: A Meta-Analysis

Objective The preferred method for screening asymptomatic people for colorectal cancer (CRC) is colonoscopy, according to the new American guidelines. The aim of our study was to perform a meta-analysis of the prospective cohorts using total colonoscopy for screening this population for CRC. We looked for the diagnostic yield of the procedure as well as for its safety in a screening setting. Methods We included papers with more than 500 participants and only those reporting diagnostic yield of adenoma (and/or advanced adenoma) and CRC. Nested analysis were performed for secondary endpoints of complications and CRC stages when this information was available. All analyses were performed with StatDirect Statistical software, version 2.6.1 (). Results Our search yielded ten studies of screening colonoscopy conducted in asymptomatic people that met our inclusion criteria, with a total of 68,324 participants. Colonoscopy was complete and reached the cecum in 97% of the procedures. Colorectal cancer was found in 0.78% of the participants (95% confidence interval 0.13–2.97%). Stage I or II were found in 77% of the patients with CRC. Advanced adenoma was found in 5% of the cases (95% confidence interval 4–6%). Complications were rare and described in five cohorts. Perforation developed in 0.01% of the cases (95% confidence interval 0.006–0.02%) and bleeding in 0.05% (95% confidence interval 0.02–0.09%). Conclusions Our findings support the notion that colonoscopy is feasible and a suitable method for screening for CRC in asymptomatic people.     

Interleukin-17A mRNA Expression is Associated with the Prognosis of Patients with Colorectal Cancer: A Pooled Meta-Analysis

Background:Interleukin-17A is a proinflammatory cytokine that is produced by TH17 cells, and plays a dual role in tumor progression, infectious diseases, and autoimmune disorders. Interleukin-17A is induced during colorectal tumorigenesis and angiogenesis, although some studies have reported an anti-tumor effect as well. The aim of our study was to assess the prognostic role of interleukin-17A in colorectal cancer and determine the potential mechanisms.Methods:The GEO database was searched using the keyword “colorectal cancer”, and 10 datasets were identified that included interleukin-17A mRNA expression and survival data of several colorectal cancer patient cohorts. The patients were stratified into the interleukin-17A^high and interleukin-17A^low groups based on the median expression level.Results:Higher interleukin-17A mRNA levels were associated with better overall survival rates and the early tumor stage, indicating a protective role of interleukin-17A in colorectal cancer. Furthermore, interleukin-17A mRNA expression also correlated positively with that of TNFS11, CCR6, and CCL20, indicating that the anti-tumor effect of interleukin-17A is likely mediated by enhancing tumor antigen presentation by dendritic cells and recruiting the activated tumor-specific CD8⁺ cytotoxic T lymphocytes. The IL-23 and STAT3 mRNA levels were also significantly higher in the interleukin-17A^high group, which points to an upstream regulatory role of IL-23/STAT3 axis. Finally, the immune checkpoints PDCD1 (PD-1) and CD274 (PDL-1) were also positively correlated with interleukin-17A mRNA expression, indicating that interleukin-17A is a promising predictor of the immunotherapeutic outcome of PD-1/PDL-1 blockade in colorectal cancer.Conclusion:Interleukin-17A mRNA is a protective factor in colorectal cancer and a promising biomarker for assessing the prognosis and immunotherapeutic response.     

Colorectal Cancer Screening: Stool DNA and Other Noninvasive Modalities

Colorectal cancer screening dates to the discovery of pre-cancerous adenomatous tissue. Screening modalities and guidelines directed at prevention and early detection have evolved and resulted in a significant decrease in the prevalence and mortality of colorectal cancer via direct visualization or using specific markers. Despite continued efforts and an overall reduction in deaths attributed to colorectal cancer over the last 25 years, colorectal cancer remains one of the most common causes of malignancy-associated deaths. In attempt to further reduce the prevalence of colorectal cancer and associated deaths, continued improvement in screening quality and adherence remains key. Noninvasive screening modalities are actively being explored. Identification of specific genetic alterations in the adenoma-cancer sequence allow for the study and development of noninvasive screening modalities beyond guaiac-based fecal occult blood testing which target specific alterations or a panel of alterations. The stool DNA test is the first noninvasive screening tool that targets both human hemoglobin and specific genetic alterations. In this review we discuss stool DNA and other commercially available noninvasive colorectal cancer screening modalities in addition to other targets which previously have been or are currently under study.     

Colorectal Cancer Pelvic Recurrences: Determinants of Resectability

PURPOSE This study was designed to identify preoperative and intraoperative features of locally recurrent colorectal cancer that predict R0 resection in patients scheduled for attempted complete resection followed by intraoperative radiation therapy.METHODS Review of a prospective data base identified 119 patients brought to the intraoperative radiation therapy suite for planned complete resection of locally recurrent rectal (n = 101) and colon (n = 18) cancer between January 1994 and November 2000. R0 resection was achieved in 61 patients. This group was compared with patients in which an R1 (n = 38), R2 (n = 7), or palliative procedure (n = 13) was performed. Variables evaluated included: tumor location, features of the primary tumor, and preoperative findings on computed tomography, magnetic resonance imaging, and history/physical. Tumor location was established by review of operative/pathologic reports and classified as axial (anastomotic/perineal), anterior (bladder/genitourinary organs), posterior (presacral), or lateral (pelvic sidewall).RESULTS When recurrence was confined to the axial location only, or axial and anterior locations, R0 resection was achieved significantly more often than when other locations were involved (P < 0.001, P = 0.003, respectively). When a lateral component was present, R0 resection was achieved significantly less often than when there was no lateral component (P = 0.002). For patients with available preoperative computed tomography and/or magnetic resonance imaging results (n = 70), the finding of lateral tumor involvement was associated with R0 resection significantly less often than when lateral disease was not identified (P = 0.004).CONCLUSIONS Pelvic recurrences confined to the axial location, or axial and anterior locations, are more likely to be completely resectable (R0) than those involving the pelvic sidewall. Efforts to enhance preoperative identification and imaging of these patients are clearly justified.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Chicago, Illinois, June 3 to 8, 2002.This work was supported, in part, by the National Cancer Institute, RO1 CA 82534-01, awarded to Jose G. Guillem, M.D., M.P.H.     

Synchronous Colorectal Neoplasms in Patients With Colorectal Cancer: Predisposing Individual and Familial Factors

PURPOSE: Patients with colorectal cancer have an increased risk for developing synchronous and metachronous neoplasms. However, besides those cases with inherited disorders predisposing to tumor multicentricity, it is unknown which patients are prone to this condition. This study was designed to identify individual and familial characteristics associated with the development of synchronous colorectal neoplasms in patients with colorectal cancer.METHODS: During a one-year period, all patients with colorectal cancer attended in 25 Spanish hospitals were included. Exclusion criteria were colorectal cancer developed in the context of familial adenomatous polyposis or inflammatory bowel disease, refusal to participate in the study, incomplete family history, and inadequate examination of the colon and rectum. In addition to demographic, clinical, pathology, molecular (microsatellite instability status), and familial characteristics, presence of synchronous colorectal neoplasms (adenoma or carcinoma) were analyzed.RESULTS: A total of 1,522 patients were included in the study. Synchronous colorectal neoplasms were documented in 505 patients (33.2 percent): adenoma (n = 411), carcinoma (n = 27), or both (n = 67). Development of these lesions was associated with male gender (odds ratio, 1.94; 95 percent confidence interval, 1.43–2.65), personal history of colorectal adenoma (odds ratio, 3.39; 95 percent confidence interval, 1.58–7.31), proximal location of primary tumor (odds ratio, 1.40; 95 percent confidence interval, 1.02–1.94), tumor TNM Stage II (odds ratio, 1.31; 95 percent confidence interval, 1.15–4.66), mucinous carcinoma (odds ratio, 1.89; 95 percent confidence interval, 1.19–2.99), and family history of gastric cancer (odds ratio, 2.03; 95 percent confidence interval, 1.17–3.52).CONCLUSIONS: Based on individual and familial characteristics associated with synchronous colorectal neoplasms, it has been possible to identify a subgroup of patients with colorectal cancer prone to tumor multicentricity with potential implications on the delineation of preventive strategies.Supported by grants from the Fondo de Investigación Sanitaria (FIS 01/0104-01, 01/0104-02, and 01/0104-03), from the Instituto de Salud Carlos III (RC03/02 and RC03/10), and from Merck, Sharp and Dhome, Spain. Virgínia Piñol, M.D. received a research grant from the Institut dInvestigacions Biomèdiques August Pi i Sunyer (IDIBAPS).Presented at the meeting of the American Gastroenterological Association, Orlando, Florida, May 17 to 22, 2003.     

结直肠癌筛查及其进展

结直肠癌(CRC)是最常见的恶性肿瘤之一,近年来我国CRC发病率总体呈现上升趋势,在消化系统恶性肿瘤中居第二位。CRC筛查可显著降低其发病率和死亡率,筛查方法多样,目前以免疫化学法粪便隐血试验(FIT)和结肠镜检查为基础的两步法筛查方案为多个国家的权威指南或共识所推荐,其他筛查方法可作为个体化的选择和补充。对于结直肠息肉超过10枚同时有CRC个人史或家族史,或结直肠息肉超过20枚的极高危人群,应行多基因种系突变检测。     

Radiofrequency Ablation of Liver Metastases from Colorectal Cancer: A Literature Review

Liver metastases occur in up to 60% of patients with colorectal cancer, and the control of liver metastases is considered to be of primary importance because it is a critical factor in determining prognosis. Radiofrequency ablation (RFA) therapy is one of the least invasive techniques for unresectable hepatic malignancies and can be performed safely using percutaneous, laparoscopic, or open surgical techniques. The local tumor progression rates after RFA for colorectal liver metastases range from 8.8% to 40.0%, and 5-year survival rates range from 20.0% to 48.5%. No prospective, randomized trials comparing the efficacy of RFA with that of surgical resection for colorectal liver metastases are currently available. However, some retrospective studies have reported that patients who received RFA had a survival rate similar to that observed in surgically treated groups, while other studies have reported better survival among patients who underwent surgical resection. The use of a laparoscopic or open surgical approach allows the repeated placement of RFA electrodes at multiple sites to ablate larger tumors. An accurate evaluation of treatment response is very important for the success of RFA therapy because a sufficient safety margin (at least 0.5 cm) can prevent local tumor progression. This review critically summarizes the current status of RFA for liver metastases from colorectal cancer.     

Colorectal Cancer Screening and Surveillance in the Elderly: Updates and Controversies

Colorectal cancer is common worldwide, and the elderly are disproportionately affected. Increasing age is a risk factor for the development of precancerous adenomas and colorectal cancer, thus raising the issue of screening and surveillance in older patients. Elderly patients are a diverse and heterogeneous group, and special considerations such as comorbid medical conditions, functional status and cognitive ability play a role in deciding on the utility of screening and surveillance. Colorectal cancer screening can be beneficial to patients, but at certain ages and under some circumstances the harm of screening outweighs the benefits. Increasing adverse events, poorer bowel preparation and more incomplete examinations are observed in older patients undergoing colonoscopy for diagnostic, screening and surveillance purposes. Decisions regarding screening, surveillance and treatment for colorectal cancer require a multidisciplinary approach that accounts not only for the patient’s age but also for their overall health, preferences and functional status. This review provides an update and examines the challenges surrounding colorectal cancer diagnosis, screening, and treatment in the elderly.     

Miniprobe Endoscopic Ultrasonography Has Limitations in Determining the T Stage in Early Colorectal Cancer

Background/Aims

Mini-probe endoscopic ultrasonography (mEUS) is a useful diagnostic tool for accurate assessment of tumor invasion. The aim of this study was to estimate the accuracy of mEUS in patients with early colorectal cancer (ECC).

Methods

Ninety lesions of ECC underwent mEUS for pre-treatment staging. We divided the lesions into either the mucosal group or the submucosal group according to the mEUS findings. The histological results of the specimens were compared with the mEUS findings.

Results

The overall accuracy for assessing the depth of tumor invasion (T stage) was 84.4% (76/90). The accuracy of mEUS was significantly lower for submucosal lesions compared to mucosal lesions (p=0.003) and it was lower for large tumors (≥2 cm) (p=0.034). The odds ratios of large tumors and submucosal tumors affecting the accuracy of T staging were 3.46 (95% confidence interval [CI], 1.05 to 11.39) and 6.25 (95% CI, 1.85 to 25.14), respectively. When submucosal tumors were combined with large size, the odds ratio was 14.67 (95% CI, 1.46 to 146.96).

Conclusions

The overall accuracy of T stage determination with mEUS was considerably high in patients with ECC; however, the accuracy decreased when tumor size was >2 cm or the tumor had invaded the submucosal layer.     

Iron Status and Colorectal Cancer in Symptomatic Elderly Patients

Objective

The study aim is to determine the relationship between the prevalence of colorectal cancer and iron status in elderly anemic and non-anemic patients.

Methods

We retrospectively investigated 359 consecutive elderly patients, aged 70 years and more, who presented to a geriatric department and who underwent a total colonoscopy. The histopathologic diagnosis of colorectal carcinoma was the primary outcome measure, and its presence was compared with the iron status, evaluated by serum ferritin and hemoglobin levels.

Results

Less than half of the patients with colorectal carcinoma had iron-deficiency anemia. The prevalence of colorectal carcinoma was similar among patients with a serum ferritin level less than 50 μg/L (16%), between 50 and 100 μg/L (20%), and greater than 100 μg/L (13%), and was not different between anemic and non-anemic patients. Sex (odds ratio for men 2.1; 95% confidence interval [CI], 1.2-3.9) and increasing age (6.6% per year; 95% CI, 1.2-12.4), but not hemoglobin and serum ferritin, were independent risk factors for colorectal carcinoma. Those with a proximal colorectal carcinoma had a lower hemoglobin and ferritin level and a higher prevalence of iron-deficiency anemia compared with patients with a distal colorectal carcinoma.

Conclusion

The prevalence of colorectal carcinoma is high in anemic and non-anemic elderly symptomatic patients, irrespective of the iron status. Therefore, the decision to order a colonoscopy in older patients should not only be considered in patients with anemia or iron deficiency but also in patients with suspicious symptoms without anemia or iron deficiency.     

A Comparison of Open vs. Laparoscopic Abdominal Rectopexy for Full-Thickness Rectal Prolapse: A Meta-Analysis

PURPOSE Using meta-analytical techniques, this study was designed to compare open and laparoscopic abdominal procedures used to treat full-thickness rectal prolapse in adults. METHODS Comparative studies published between 1995 and 2003, cited in the literature of open abdominal rectopexy vs. laparoscopic abdominal rectopexy, were used. The primary end points were recurrence and morbidity, and the secondary end points assessed were operative time and length of hospital stay. A random effect model was used to aggregate the studies reporting these outcomes, and heterogeneity was assessed. RESULTS Six studies, consisting of a total of 195 patients (98 open and 97 laparoscopic) were included. Analysis of the data suggested that there is no significant difference in recurrence and morbidity between laparoscopic abdominal rectopexy and open abdominal rectopexy. Length of stay was significantly reduced in the laparoscopic group by 3.5 days (95 percent confidence interval, 3.1–4; P < 0.01), whereas the operative time was significantly longer in this group, by approximately 60 minutes (60.38 minutes; 95 percent confidence interval, 49–71.8). CONCLUSIONS Laparoscopic abdominal rectopexy is a safe and feasible procedure, which may compare equally with the open technique with regards to recurrence and morbidity and favorably with length of stay. However large-scale randomized trials, with comparative, sound methodology are still needed to ascertain detailed outcome measures accurately.     

Postoperative Fever and Survival in Patients after Open Resection for Colorectal Cancer: A Long-Term Follow-Up Study of 2,311 Prospectively Enrolled Patients

Purpose  Two reports on the impact of postoperative fever on survival after surgery in patients with colorectal cancer yielded contradictory results. Our study examined possible associations between postoperative fever and long-term survival of patients who underwent resection of colorectal cancer. Methods  We investigated 2,311 consecutive patients who underwent elective open colorectal resection for primary colorectal cancer at a single institution between 1995 and 1998. The primary end points were cancer-specific and overall survival. Multiple covariate impact of risk factors on survival rates was assessed by Cox regression analysis. Results  A total of 252 patients (12.2 percent) developed postoperative fever. The most important independent risk factor for postoperative fever was postoperative morbidity (odds ratio, 4.9; 95 percent confidence interval, 3.7–6.6) followed by blood transfusion (1.7; 1.2–2.2), Stage IV disease (1.6; 1.1–2.2), male gender (1.4; 1.0–1.9), and rectal cancer (1.4; 1.0–1.8). Cox regression modeling indicated that stage, histology, tumor location, and blood transfusion were statistically significant covariate predictors for cancer-specific survival. Postoperative fever was not independently associated with cancer-specific or overall survival. Conclusions  This study did not support the hypothesis that postoperative fever is an independent prognostic factor after colorectal resection for primary colorectal cancer.     

p53 Status and Its Prognostic Role in Extrahepatic Bile Duct Cancer: A Meta-Analysis of Published Studies

The dysfunction of p53 is the most common genetic alteration in human cancer. A variety of studies have investigated the clinicopathologic correlation of p53 and its impact on patient survival in different types of cancer. For extrahepatic bile duct cancer (EBDC), however, the results were limited and conflicting. In this study, we performed an investigation to confirm whether there was a correlation between p53 status and some routine parameters. To further observe the impact of p53 on the survival of EBDC patients, a meta-analysis based on published studies was conducted. Candidate studies were searched from PubMed, EMBASE, and ISI Web of Science. Our results demonstrated that there were significant correlations between p53 expression and some clinicopathological parameters. Furthermore, the pooled results of the meta-analysis showed that the combined hazard ratio (HR) estimate for overall survival (OS) was 1.53 (95% CI, 1.10–2.14) and 1.23 (95% CI, 0.93–1.75) in univariate and multivariate analysis, respectively. In conclusion, the high level of p53 appears to be an effective prognostic factor to OS of EBDC patients. However, some limitations unavoidable in this meta-analysis and problems of previous p53 studies in EBDC mean that further studies are necessary before significant conclusions can be made.     

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.