p53 codon 72 polymorphism and susceptibility malignancy of colorectal cancer in Taiwan

Purpose The p53 tumor suppressor gene plays two important roles in genomic stability: blocking cell proliferation after DNA damage until it has been repaired, and starting apoptosis if the damage is too critical. A recent report suggests that a polymorphism of the p53 tumor suppressor gene that results in the substitution of a proline residue with an arginine residue at position 72 of the p53 protein might act as a risk factor in the malignant transformation of colorectal adenoma to cancer.Methods In our study, the samples consisted of 150 patients were analyzed for the mutation in the p53 gene. The age of 150 patients (46 women and 104 men) ranged from 30 to 91 years (mean age 68.46 years).Results The polymorphism showed 52.04% mutant in the codon 72 of exon 4 in the Taiwanese population. Both of the chi-square for trend test (chi-square=4.97, p=0.034) and logistic regression (p=0.037, odds ratio=1.699) showed significant differences in the distribution of polymorphism of codon 72 in the p53 gene and Dukes classification of colorectal cancer.Conclusions There were significant relationship between the polymorphism of codon 72 and the malignancy of colorectal cancer in Taiwanese population. There is 1.70 times in each grade change (Dukes A–D) more risk of CCC polymorphism than that of CCG polymorphism of codon 72 of exon 4.     

骨桥蛋白mRNA在大肠癌患者外周血中的表达及其临床意义

目的检测大肠癌外周血中的骨桥蛋白（OPN）mRNA的表达,探讨其与临床病理分期及淋巴转移的关系。方法应用逆转录聚合酶链反应技术检测52例大肠癌患者（大肠癌组）外周血单个核细胞中OPN mRNA的表达,并以33例大肠腺瘤患者（大肠腺瘤组）及20例健康人（健康对照组）外周血作为对照。结果 OPN mRNA在大肠癌组外周血单个核细胞中表达的阳性率为65.4%,大肠腺瘤组OPN mRNA阳性率为33.3%,健康对照组外周血中均无靶OPN mRNA表达。大肠癌组与大肠腺瘤组OPN mRNA阳性表达率均高于健康对照组（P均〈0.01）,大肠癌组OPN mRNA阳性表达率高于大肠腺瘤组（P〈0.05）。随着大肠癌Dukes分期的升高,其外周血单个核细胞中OPN mRNA表达阳性率逐渐增高（P〈0.05）。有淋巴结转移的表达阳性率高于无淋巴结转移及对照组（P均〈0.01）;无淋巴结转移患者与大肠腺瘤组之间差异无统计学意义。结论外周血单个核细胞中OPN mRNA阳性表达对大肠癌的淋巴转移及预后判断具有一定价值。     

Serum Carcinoembryonic Antigen in Relation to Survival,DNA Ploidy Pattern,and Recurrent Disease in 406 Colorectal Carcinoma Patients

Serum carcinoembryonic antigen (CEA) levels in relation to survival, flow cytometric DNA ploidy pattern, Dukes stage, and recurrent disease was prospectively evaluated in 406 patients with colorectal carcinoma. In 246 patients (61%) the carcinomas were DNA aneuploid. Increased preoperative CEA levels (>5 μg/l) were found in 151 of 363 evaluable patients (42%). Dukes stage-B patients with preoperative CEA elevation showed significantly poorer prognosis than those with normal CEA values (p = 0.001). A weak but significant correlation was found between preoperative CEA level and Dukes stage (Kendall's α = 0.25, p < 0.01). Of 50 evaluable patients with clinical recurrence and postoperative normal or normalized CEA levels, 28 (56%) had a rise in CEA before or at the time of clinical recurrence. The sensitivity of the CEA test for primary and for recurrent disease was not significantly different in the DNA aneuploid and the DNA near-diploid groups.     

Risk‐stratified intensive follow up for treated colorectal cancer – realistic and cost saving?

Objective Intensive follow‐up post surgery for colorectal cancer (CRC) is thought to improve long‐term survival principally through the earlier detection of recurrent disease. This paper aims to calculate the additional resource and cost implications of intensive follow up post‐CRC resection, examine the possibility of risk‐stratifying this follow up to those at highest risk of recurrence and investigating the impact that population screening might have on the future cost and outcomes of follow up. Method Two follow‐up regimens were constructed: the ‘standard’ follow‐up protocol used the principles of the British Society of Gastroenterology (BSG) guidelines whilst the ‘intensive’ follow‐up protocol used the most intensive arm of the follow up after colorectal surgery (FACS) trial. Using ONS data, the number of CRC diagnosed in a given year was calculated for 2003 and projected for 2016 based on the population of England and Wales. The resource requirements and costs of follow up over a 5‐year period were then calculated for the two time periods. Risk stratifying entry to follow up and the introduction of population CRC screening were then considered. Results For the 2003 cohort, an intensive follow‐up program would detect 853 additional resectable recurrences over 5 years with 795 fewer subjects requiring palliative care. An additional 26 302 outpatient appointments, 181 352 CEA tests and 79 695 CT scans over 5 years would be required to achieve this. The cost of investigating subjects who would never develop detectable recurrences was £15.6 million. The cost per additional resectable recurrence was £18 077, a figure also found for a nonscreened population in 2016. An identical intensive follow‐up policy with biennial FOBT screening in 2016 saw the cost per additional resectable recurrence rise to £36 255. Conclusion Intensive follow up will detect considerably more resectable recurrences but at considerable cost and it is unclear if such follow up will be achievable in an already over‐stretched NHS. If population‐based CRC screening increases the number of Dukes A cancers this may offer the possibility of risk‐stratifying future follow up to those at highest risk of recurrence; minimizing tests on those who will never have recurrent disease and better utilizing our scarce resources.     

Relative prognostic value of the Dukes and the Jass systems in rectal cancer

A comparison of the prognostic values of the Dukes and Jass systems were performed with 722 patients with rectal cancer enrolled in the National Surgical Adjuvant Breast and Bowel Projects, protocol R-01. The Jass system revealed four prognostic groups when all patients or only Dukes' B and C cases were examined; however, the magnitude of differences between groups I and II and III and IV were small. Dukes' classification, as defined in this study, revealed five prognostic groups. A statistically strong association between the Jass and Dukes systems was observed. Although histologic grade permitted further prognostic discrimination of all Dukes stages except A, only the Jass system allowed for the subdivision of C cases with up to four nodes positive for metastases. Those in that group had survival rates comparable to B cases (no nodal involvement) when scores of I and II were found. The distributions of the patients in the extremes of the Jass and Dukes systems (C2 as defined) were almost similar. The findings indicate that the Jass system is a valid prognostic method for patients with rectal carcinoma. In this material, however, it basically allowed for only two major prognostic groups whereas five were noted by the Dukes method. These results, as well as the more objective nature of Dukes' classification, warrant its continued use for prognosis and therapeutic decisions for patients with rectal cancer. See Appendix. This investigation was supported by Public Health Service Grants from the National Cancer Institute (NCI-U10-A-34212) and by a grant from the American Cancer Society (ACR-RC-13).     

Character of the invasive margin in colorectal cancer

PURPOSE: The clinical significance and prognostic value of the histopathologic parameters used in both the Dukes and Jass classifications were evaluated to select those with an independent effect on survival after radical surgery for colorectal cancer. METHODS: The depth of local spread (limited to the bowel wall or extended beyond it), the number of metastatic lymph nodes (none, 1–4, more than 4), the character of the invasive margin (pushing or infiltrating), and the presence or absence of conspicuous peritumoral lymphocytic infiltration were assessed in 235 patients who had undergone radical resection for colorectal cancer. The influence of these variables on survival was studied by univariate and multivariate analysis. RESULTS: No significant difference in survival was found between patients with conspicuous peritumoral infiltrate and those without it; moreover, multivariate analysis failed to show any independent prognostic value for either lymphocytic infiltration or depth of local invasion. However, the character of the invasive margin and the number of metastatic lymph nodes were identified as the only variables with any independent importance on survival. Based on these data, a new prognostic model may be proposed; it uses the character of the infiltrative margin as a discriminating factor among patients within the lymph node-negative (Dukes A and B stages) and lymph node-positive (Dukes C1 and C2 subsets) groups. A good prognosis for Dukes A, B, and C1 patients was associated with pushing tumors; C1 and C2 patients with infiltrating tumors had a poor prognosis. On the whole, the new prognostic model has allowed for the placement of 59.6 percent of our patients into groups that provide a confident prognosis. The clinical outcome of Dukes A and B patients with infiltrating tumors is still uncertain. CONCLUSIONS: The character of the invasive margin is an important prognostic factor in colorectal cancer. The association of this parameter with the traditional Dukes classification may provide additional useful prognostic information and aid in the selection of those patients who could most benefit from adjuvant therapy.     

Lymph node examination as a predictor of long-term outcome in Dukes B colon cancer

Background  Mortality from cancer recurrence in Dukes B patients is approximately 25–30%. Outcome in Dukes B patients improves in direct relation to the number of lymph nodes examined. Examining fewer lymph nodes risks understaging and also such patients are less likely to receive chemotherapy. The aim of this study was to assess the impact of the number of lymph nodes examined on recurrence and mortality in Dukes B colon cancers. Materials and methods  A retrospective database was constructed of 328 consecutive patients who underwent resection for Dukes B colorectal cancer between January 1993 and December 2001 at Middlemore Hospital. Patients with incomplete data, previous colorectal cancer, or perioperative deaths were excluded as were cases of rectal cancer. Data for the remaining 216 patients was subjected to multivariate and logistic regression analysis with ‘patient death’ or ‘cancer recurrence’ (CRec5) within 5 years as endpoints. A graph was constructed depicting CRec5 as broken down by lymph node strata. Receiver operator characteristic (ROC) curves were constructed for mortality and CRec5. Results  The mean number of lymph nodes examined was 16.0 (median 14; range 2–48). The mean number of lymph nodes examined in those who died within 5 years was 12.8 vs. 17.5 in those who remained alive (p = 0.0027). The mean number of lymph nodes examined in those with evidence of recurrence within 5 years was 11.8 vs. 17.1 in those without recurrence (p = 0.0007). Analysis at various lymph node strata showed a sharp and statistically significant drop in the recurrence rate after the 16the node mark. The ROC curve for CRec5 showed that examination of 12 lymph nodes provided maximum sensitivity (0.60) and specificity (0.64). Conclusion  Examination of more than 16 lymph nodes is associated with a significant reduction in cancer recurrence. This supports the current clinical practice of harvesting and analysing as many nodes as possible during surgical resection and pathological analysis.     

结直肠癌患者手术前后血清IGF-1水平变化及临床价值分析

目的 用酶联免疫吸附测定法检测结直肠癌患者手术前后血清 IGF-1的含量,并探讨其手术前后血清水平变化及在结直肠癌发生发展中的作用。方法 选取在佳木斯大学附属第一医院首次确诊并行结直肠癌切除术患者共30例为观察组,于手术前清晨及术后30 d采集空腹静脉血。选取同时期体检健康者30例为对照组,采集体检当日空腹静脉血。用Elisa法检测两组患者血清IGF-1的含量,观察血清IGF-1含量在两组中的变化规律,分析IGF-1与结直肠癌临床各参数的关系。结果 观察组术前血清IGF-1水平为（200.48±42.25）ng/ml,高于观察组术后的（164.52±35.45）ng/ml和对照组的（146.26±43.14）ng/ml,差异有统计学意义（P＜0.05）;观察组术后血清IGF-1水平较对照组稍高,但差异无统计学意义（P＞0.05）;高分化、中分化者血清IGF-1水平低于低分化者,差异有统计学意义（P＜0.05）;Dukes分期中A+B和C+D期之间比较,差异有统计学意义（P＜0.05）。结论 结直肠癌患者血清IGF-1参与结直肠癌的病变过程,是一种有促进细胞增殖、分化等多种生物学活性的细胞因子,可能作为结直肠癌发生、发展的重要预测指标及手术切除后手术效果的评定指标之一。     

Prognostic Factors and the Role of Adjuvant Chemotherapy in Post-curative Surgery for Dukes B and C Colon Cancers and Survival Outcomes: a Malaysian Experience

Background: Adjuvant chemotherapy improves survival in Dukes C colon cancers post-curative resection.However, the evidence for a role with Dukes B lesions remains unproven despite frequent use for diseasecharacterized by poor prognostic features. In view of limited Asia-specific data, this study aimed to determinesurvival outcomes and identify prognostic factors in a tertiary teaching hospital in Malaysia. Materials andMethods: A total of 116 subjects who underwent curative surgery with and without adjuvant chemotherapy forDuke B and C primary colon adenocarcinomas diagnosed from 2004-2009 were recruited and data were collectedretrospectively. Five-year overall survival (OS) and disease free survival (DFS) were analysed using Kaplan-Meiersurvival analysis and log-rank (Mantel-Cox) test. Prognostic factors were determined using Cox proportionalhazards regression with both univariate and multivariate analyses. Results: The survival analysis demonstrateda 5-year OS of 74.0% for all patients, with 74.9% for Dukes C subjects receiving chemotherapy compared to28.6% in those not receiving chemotherapy (p=0.001). For Dukes B disease, the 5-year survival rate was 82.6%compared to 75.0% for subjects receiving and not receiving chemotherapy, respectively (p=0.17). Independentprognostic factors identified included a CEA level more than 3.5 ng/ml (hazard ratio (HR)=4.78; p=0.008),serosal involvement (HR=3.75; p=0.028) and completion of chemotherapy (HR= 0.20; p=0.007). Conclusions:In a regional context, this study supports current evidence from the West that adjuvant chemotherapy improvessurvival in Dukes C colon cancers post curative surgery. However, although a clear benefit has yet to be provenfor Dukes B disease, our results suggest survival improvement in selected cases.     

E-cad、Snail表达与Dukes B期大肠癌浸润、转移、预后的关系

目的研究E- cad、Snail表达与大肠癌侵袭、转移和预后的关系。方法采用免疫组化EnVision法,分别检测E- cad、Snail在正常大肠黏膜上皮、大肠腺瘤及大肠癌患者癌组织中的表达。结果 E- cad的表达与肿瘤分化程度、浸润深度、静脉、淋巴管侵犯、淋巴结转移与否及Dukes分期状况密切相关（均P＜0.05）,而与年龄、性别、肿瘤大小、肿瘤病理类型无相关性（均P＞0.05）。45例Dukes B期的大肠癌患者中7例E- cad染色阴性,其1、3、5年生存率分别为85.71％、57.14％、0.00％;38例为中度阳性或强阳性,其1、3、5年生存率分别为97.37％、65.79％、39.47％,两者比较有统计学差异（P＜0.01）。Snail表达与肿瘤病理类型、分化程度、浸润深度、静脉、淋巴管侵犯、淋巴结转移与否及Dukes分期明显相关（均P＜0.05）,而与年龄、性别、肿瘤大小无相关性（均P＞0.05）。45例Dukes B期的大肠癌患者中26例Snail染色阴性,其1、3、5年生存率分别为100.00％、69.23％、42.31％;19例为中度阳性或强阳性,其1、3、5年生存率分别为89.47％、57.89％、26.32％,两者比较有统计学差异（P＜0.01）。多因素分析结果显示：肿瘤淋巴结转移、Dukes分期、E- cad表达强度、Snail表达强度可预示患者术后生存情况（均P＜0.05）。E-cad与Snail在大肠癌组织中的表达呈显著负相关（r=-0.508,P＜0.01）。结论 E- cad与Snail可作为大肠癌患者的独立预后指标,预示患者术后生存情况。Dukes B期大肠癌患者中,E- cad阴性者预后明显较阳性者为差;Snail阳性者的预后明显较阴性者为差。