Temporal trends in the proportion cured for cancer of the colon and rectum: a population-based study using data from the Finnish Cancer Registry

Colorectal cancer is the third most common cancer worldwide and the second most common cancer in Europe. Cumulative relative survival curves for both cancer of the colon and cancer of the rectum generally plateau after approximately 6-8 years. When this occurs, "population" or "statistical" cure is reached. We analyzed data from the Finnish Cancer Registry over a 50-year period using methods that simultaneously estimate the proportion of patients cured of disease (the cure fraction) and the survival time distribution of the "uncured" group. Our primary aim was to investigate temporal trends in the cure fraction and median survival of the uncured by age group for both cancer of the colon and rectum. For both cancers, the cure fraction has increased dramatically over time for all age groups. However, the difference in the cure fraction between age groups has reduced over time, particularly for cancer of the colon. Median survival in the uncured has also increased over time in all age groups but there still remains an inverse relationship between age and median survival, with shorter median survival with increasing age. The reasons for these impressive increases in patient survival are complex, but are highly likely to be strongly related to many improvements in cancer care over this same time period.     

Survival of patients with oesophageal and gastric cancers in Europe

The EUROCARE study is a European Union project to collect survival data from population-based cancer registries and analyse them according to standardised procedures. We investigated and compared oesophageal and gastric cancer survival in 17 countries between 1985 and 1989. Time trends in survival over the 1978–1989 period were also investigated in 13 countries. The overall European 1-year relative survival rates were 33% for oesophageal cancer and 40% for gastric cancer. The corresponding 5-year relative survival rates were 10 and 21%, respectively. Important intercountry survival differences exist within Europe for oesophageal and gastric cancer. Taking the European average as the reference, the relative risk (RR) of death at 5 years was at least 30% higher in Denmark, Poland, Estonia and Slovenia for oesophageal cancer and in Denmark, England, Scotland and Poland for gastric cancer. In the other countries survival figures were close to the European average. Gender had little influence on survival, whilst age at diagnosis was inversely related to prognosis. There was a slight improvement between 1978 and 1989 in 5-year overall relative survival rates for both oesophageal cancer (RR=0.80, 95% confidence interval (CI) 0.72–0.90) and gastric cancer (RR=0.88, 95% CI 0.82–0.94). Differences in quality of care and stage at diagnosis can explain in part the differences in survival found in the EUROCARE countries. Significant improvement in prognosis has still to be achieved.     

Molecular detection of p16 promoter methylation in the serum of recurrent colorectal cancer patients

We previously proved that p16 promoter methylation present in the tumors of colorectal cancer patients can be detected in the serum of those same patients using methylation-specific PCR (MSP). To seek the possibility that this technique could be applied to the monitoring of cancer recurrence, we examined the p16 methylation using MSP. We detected tumor DNA in the serum of 31 of 45 (69%) patients with recurrent colorectal cancer. No methylation was found in serum DNA of 50 patients with colorectal cancers whose corresponding tumor DNA had no methylation in p16 promoter. These results suggested that MSP might be a sensitive and useful method to detect recurrent colorectal cancer in serum.     

Liquid biopsies in gastrointestinal malignancies: when is the big day?

Introduction: Tumor tissue sample is currently the gold standard for diagnosing gastrointestinal cancers, but also for genomic/immune component analyses that can help in the selection of therapy. However, this approach of studying a ‘representative’ sample of the tumor does not address inherent heterogeneity. Liquid biopsies, mainly represented by circulating tumor cells, circulating tumor DNA, tumor exosomes, and microRNAs, have the potential to assess various biomarkers for early detection of cancer, carrying out genomic/immune profiling for not only selection of appropriate therapy but also to monitor effect of therapy.

Areas covered: This review summarizes the current evidence in the literature on liquid biopsies in gastrointestinal cancers concerning diagnosis, prognosis, and response to therapy. The following terms were used in PubMed: ‘esophageal’, ‘gastric’, ‘colorectal’, ‘cancer’, ‘circulating tumor cells’, ‘circulating tumor DNA’, microRNA’, ‘diagnosis’, ‘prognosis’, ‘response’, ‘resistance’.

Expert commentary: Data increasingly supports the potential of liquid biopsies for early detection, selection of therapy, and monitoring response to therapy. One major question is whether assaying various components of the blood would accommodate considerable context-dependent heterogeneity of gastrointestinal tumors. There are many potential strategies to exploit liquid biopsy use. To put them in to perspective, well-designed and meticulous prospective studies will be needed to prove their usefulness.     

DNA甲基化与胃肠道肿瘤研究进展

目的 主要从基因DNA甲基化修饰与胃肠肿瘤发生发展、化疗药物靶点、作为早期诊断标志物等进展进行综述.方法 应用PubMed及中国知网数据库检索系统,以中文关键词"DNA甲基化、胃癌、结直肠癌、早期诊断、靶向药物"和英文关键词"DNA methylation、gastric cancer、colorectal cance...     

结直肠癌合并肠梗阻56例诊治分析

目的：总结结直肠癌合并肠梗阻的诊断和治疗经验,探讨其漏诊原因及手术方法的选择。方法：回顾分析我院2001年2月-2007年5月56例梗阻性结直肠癌病人的临床特点及根据患者不同情况分别行一期手术和分期手术。结果．56例患者均经手术治疗,出现并发症4例,死亡1例,病死率为3．6％,其余均痊愈出院。结论：结直肠癌合并肠梗阻临床特点是：左侧结肠梗阻多见;晚期病例多见;老年患者多见。外科治疗的原则是解除梗阻,尽量切除肿瘤。应根据患者的具体情况选择合适的手术方式。     

Patterns of failure following surgery alone for colorectal carcinoma

Two hundred fifty-one patients with colorectal carcinoma were studied following complete primary resection to determine patterns of failure. Seventy-two patients (29%) subsequently developed failures: Local failure (LF) occurred as the only failure in 49% of the failure group and as some component in 81%; distant metastases (DM) occurred in 19% and 47%, respectively. The groups at highest risk for local failure were those with extension of tumor through the bowel wall whether the nodes were involved or not. Furthermore, those with gross extension of disease through the wall developed a significantly higher incidence of distant metastases compared to those with microscopic extension through the wall (P less than 0.005). The absolute 5-year survival rate for those with tumor through the wall vs within the wall was 40% and 79%, respectively. Adjuvant therapy was discussed in view of the ability to identify subgroups of patients at highest risk for local vs distant failures.     

表观遗传学干预对结直肠癌细胞株p33ING1b基因表达及生物学特性影响

目的通过表观遗传学干预,研究p33ING1b启动子甲基化和组蛋白乙酰化状态、基因和蛋白的表达及其细胞增殖能力的改变,探讨结直肠癌中p33ING1b转录抑制的表观遗传机制。方法通过曲古抑菌素A及5-氮-2′-脱氧胞苷,对结直肠癌细胞株HT29、LOVO、HCT116和COLO205行恢复乙酰化和去甲基化干预,分单独用药组和联合用药组。RT-PCR结合Real-time qPCR方法检测其p33ING1bmRNA表达的变化,nMSP法分析其p33ING1b启动子甲基化状态的改变,ChIP法检测其p33ING1b乙酰化状态的改变,蛋白质印迹法检测p33ING1b蛋白的表达,MTT法检测细胞的增殖能力。结果曲古抑菌素A及5-氮-2′-脱氧胞苷可逆转结直肠癌细胞株的甲基化及乙酰化状况。2种药物干预后,4种结直肠癌细胞株各组间p33ING1bmRNA表达,差异有统计学意义,HCT116:F=1 690.446,P<0.001;HT29:F=284.474,P<0.001;LOVO:F=2 930.284,P<0.001;COLO205:F=33.540,P<0.001;p33ING1bmRNA蛋白表达差异有统计学意义,HCT116:F=32.606,P<0.001;HT29:F=33.422,P<0.001;LOVO:F=13.975,P<0.01;COLO205:F=7.119,P<0.05,细胞增殖能力差异有统计学意义,HCT116:F=7.327,P<0.05;HT29:F=17.642,P<0.001;LOVO:F=7.035,P<0.05;COLO205:F=9.008,P<0.01。联合使用两种药物对p33ING1bmRNA的表达具有协同作用。结论 p33ING1b基因甲基化和去乙酰化可抑制抑癌基因p33ING1b转录,使用甲基化抑制剂及去乙酰化抑制剂可逆转这一效应,且两者具有协同作用,这为表观基因治疗提供了新的思路。     

Colorectal carcinoma: Analysis of management in two medical eras

Trends in presentation, diagnosis, management, and outcome were analyzed for 503 patients with colorectal cancer seen at the UCLA Medical Center between 1960 and 1970 (Group A; n = 210) and 1980 and 1985 (Group B; n = 293). Patients in the latter group exhibited a shift in site to the right side of the colon (18% in Group A vs. 31% in Group B; P < .01), an increase in the number of primary resections without colostomy (38% vs. 61%; P < .01), a lower overall complication rate (28% vs. 18%; P = .01), and a decline in 30-day mortality (6.2% vs. 2%; P = .01). Although little difference was seen in detection of asymptomatic tumors, earlier lesions were treated in the latter group, accounting for substantially reduced rate of recurrence (69% in Group A vs. 44% in Group B; P < .01). Future management should include an emphasis on earlier detection in order to continue the trend toward enhanced survival. © 1993 Wiley-Liss, Inc.     

Aging-like Spontaneous Epigenetic Silencing Facilitates Wnt Activation,Stemness, and BrafV600E-Induced Tumorigenesis

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XELOX双周方案治疗晚期胃肠癌的近期疗效

目的 观察奥沙利铂联合卡培他滨(XELOX)双周方案治疗晚期胃、结直肠癌的临床疗效和不良反应。方法 46例晚期胃、结直肠癌患者应用奥沙利铂85mg/m2,静滴2h,d1;卡培他滨 （900～1000）mg/m2,一日分两次,口服,d1～10;14d为1周期,4周期评价疗效。结果 46例均可评价疗效,CR 4例,PR 24例,RR 65.2％;不良反应主要为I～Ⅱ度血液学毒性,恶心、呕吐,末梢神经异常及手足综合征。结论 奥沙利铂联合卡培他滨(XELOX)双周方案治疗晚期胃、结直肠癌疗效确切,耐受性好,值得临床推广应用。     

Clinicopathological features and prognostic impact of dirty necrosis in metastatic lung cancers from the colon and rectum

Dirty necrosis (DN) is a form of tumor necrosis (TN) with prominent neutrophil infiltration and cell detritus in the necrotic foci. This study aimed to characterize the clinicopathological features of DN in metastatic lung cancers of the colon and rectum (MLCRs). A total of 227 patients who underwent pulmonary metastasectomy and complete resection for MLCR were included in this study. TN was evaluated using digitally scanned resection specimens. These slides were immunostained for biomarkers of NETosis (citrullinated histone H3 [citH3] and myeloperoxidase [MPO]), and the area positive for citH3 and MPO was further quantified. TN was observed in 216 cases (95.2%), and 54 (25.0%) of these cases had DN. The presence of TN was not associated with a worse prognosis; however, patients with DN had a significantly shorter overall survival than those without DN (p < 0.01). Furthermore, the presence of DN was a poor prognostic factor in both the univariate and multivariate analyses. Immunohistochemical analysis revealed that the percentage of citH3-positive and MPO-positive areas in the DN-positive cases was significantly higher than that in the DN-negative cases (p < 0.01 and p < 0.01, respectively). In surgically resected MLCR, DN is the characteristic TN subtype associated with poor prognosis and neutrophil extracellular traps (NETs).     

Aberrant promoter methylation of multiple genes during multistep pathogenesis of colorectal cancers

Aberrant methylation of 5'gene promoter regions associated with gene silencing is an epigenetic phenomenon responsible for silencing of tumor suppressor genes in many cancer types. The aims of our study were to study the role of methylation of a large panel of genes during multistage pathogenesis and to correlate our findings with patient age and other clinico-pathological features. We investigated the aberrant promoter methylation profile of 19 genes in 92 colorectal cancers (CRCs) and corresponding nonmalignant epithelia (NME) (n = 57), and selected 15 genes for studying 26 colorectal adenomas (CAs). On the Basis of our results, the genes could be divided into 3 groups. Group 1 consisted of 13 genes whose methylation was tumor-specific. For 8 of these genes, the methylation frequencies in CAs were similar to those of CRCs, but significantly different from the frequencies in NME. Group 2, consisting of 2 genes demonstrating little or no methylation, were present in any sample type. In Group 3, consisting of 4 genes, relatively frequent methylation was present in both CRCs and NME, and the differences between these specimen types were not significant. Methylation of Group 1 genes were tightly correlated with each other, and these genes demonstrated increased methylation frequencies in CRCs with increasing age. Methylation was not correlated with other clinico-pathological features. In general, methylation frequencies of CAs were intermediate between CRCs and NME. Our study constitutes the most comprehensive methylation profile of CRCs, demonstrates that methylation commences early during CRC pathogenesis and is an age-related phenomenon.     

DNA甲基化在肺癌中的研究进展

表观遗传学主要是研究基因表达的变化,而这种变化能够通过减数分裂遗传,但不涉及有关基因碱基序列的改变.随着肿瘤发病机制研究在分子生物学方面的逐步深入,发现DNA甲基化、非编码RNA表达调控和组蛋白的修饰等表观遗传学(epigenetics)改变引起的调控机制异常与人体多种恶性肿瘤的发生发展过程有着密切联系.研究表明抑癌基因启动子区高度DNA甲基化状态在恶性肿瘤的发生发展和侵袭转移中发挥着重要作用.在肺癌发生的早期,出现很多DNA甲基化状态的改变.因此,甲基化检测可能对肺癌患者的早期诊断、治疗及预后评估具有重要意义.     

Trend of incidence, subsite distribution and staging of colorectal neoplasms in the 15-year experience of a specialised cancer registry.

BACKGROUND: Two-thirds of colorectal malignancies are localised in the left colon and rectum. Recent studies suggest a trend towards an increase of right-sided tumours which might have important implications for screening and surveillance. A colorectal cancer registry was set up in Modena, northern Italy, with the purpose of examining incidence, subsite distribution and staging of colorectal malignancies over a 15-year period. PATIENTS AND METHODS: From 1984 to 1998, 2517 tumours in 2462 patients were detected and staged with the tumour node metastasis (TNM) system. The 'right colon' was considered from caecum to splenic flexure; the 'left colon' included descending and sigmoid colon; and the 'rectum' included rectosigmoid junction, ampulla and anus. RESULTS: Cancer incidence showed an overall increase. Considering the various subsites, an increase of 33.7% in all colonic segments was shown whereas rectal tumours tended to decline. TNM staging showed a gradual increase of localised lesions (41.2% in 1984 versus 53.3% in 1998), with a proportional reduction of advanced tumours. CONCLUSIONS: Our study indicates an increase of tumour incidence in all colonic segments more than a shift to the right colon. TNM staging tended to improve with an appreciable increase of localised lesions. These findings could be consequent to a more extensive use of colonoscopy.     

Relation between normal rectal methylation,smoking status,and the presence or absence of colorectal adenomas

BACKGROUND:

Colorectal cancer (CRC) is 1 of the leading causes of death in the Western world. CRC develops from premalignant lesions, chiefly colorectal adenomas. Currently, the most accurate and recommended screening method for finding colorectal adenomas is colonoscopy performed on all individuals aged >50 years. However, the costs and risks associated with this procedure are relatively high. The objectives of the current study were to correlate epigenetic alterations that occur in normal rectal mucosa, smoking status, and age with the presence or absence of concomitant colorectal adenomas and to assess the potential clinical value of methylation in normal rectal biopsies as a screening assay for the presence of polyps and, hence, the need for a full colonoscopy.

METHODS:

One hundred thirteen normal rectal mucosal biopsies from 113 patients were studied. DNA was extracted, modified with sodium bisulfite, and subjected to real‐time quantitative, methylation‐specific polymerase chain reaction analysis for the following genes: adenomatous polyposis coli (APC); cadherin 1, type 1, E‐cadherin (epithelial) (CDH1); estrogen receptor 1 (ESR1); cytokine high in normal 1 (HIN1); hyperplastic polyposis protein 1 (HPP1); O‐6 methylguanine‐DNA methyltransferase (MGMT); neural epidermal growth factor‐like 1 (NELL1); splicing factor 3B, 14‐kDa subunit (p14); cyclin‐dependent kinase (CDK) inhibitor 2B (inhibits CDK4) (p15); retinoic acid receptor beta (RARβ); somatostatin (SST); tachykinin, precursor 1 (TAC1); and tissue inhibitor of metalloproteinase (TIMP) metallopeptidase inhibitor 3 (TIMP3). Data were then analyzed using several proprietary software programs.

RESULTS:

By using several sets of genes, clinical characteristics, and multivariate analyses, the authors developed a prediction model for the presence of concomitant colorectal adenomas at the time of rectal biopsy. They also observed strong correlations between smoking status and rectal methylation pattern and between smoking status and the presence or risk of concomitant adenomas.

CONCLUSIONS:

A prediction model was developed for the presence of colorectal adenomas based on gene methylation patterns in the normal rectum. The results indicated that these genes may be involved in early stages of adenoma formation. The observed epigenetic alterations in these markers may be caused in part by the effects of smoking and/or age. Normal rectal methylation may be useful as a biomarker for narrowing the population in need of screening colonoscopy. Cancer 2010. © 2010 American Cancer Society.     

Colorectal cancer statistics, 2023

Colorectal cancer (CRC) is the second most common cause of cancer death in the United States. Every 3 years, the American Cancer Society provides an update of CRC statistics based on incidence from population-based cancer registries and mortality from the National Center for Health Statistics. In 2023, approximately 153,020 individuals will be diagnosed with CRC and 52,550 will die from the disease, including 19,550 cases and 3750 deaths in individuals younger than 50 years. The decline in CRC incidence slowed from 3%–4% annually during the 2000s to 1% annually during 2011–2019, driven partly by an increase in individuals younger than 55 years of 1%–2% annually since the mid-1990s. Consequently, the proportion of cases among those younger than 55 years increased from 11% in 1995 to 20% in 2019. Incidence since circa 2010 increased in those younger than 65 years for regional-stage disease by about 2%–3% annually and for distant-stage disease by 0.5%–3% annually, reversing the overall shift to earlier stage diagnosis that occurred during 1995 through 2005. For example, 60% of all new cases were advanced in 2019 versus 52% in the mid-2000s and 57% in 1995, before widespread screening. There is also a shift to left-sided tumors, with the proportion of rectal cancer increasing from 27% in 1995 to 31% in 2019. CRC mortality declined by 2% annually from 2011–2020 overall but increased by 0.5%–3% annually in individuals younger than 50 years and in Native Americans younger than 65 years. In summary, despite continued overall declines, CRC is rapidly shifting to diagnosis at a younger age, at a more advanced stage, and in the left colon/rectum. Progress against CRC could be accelerated by uncovering the etiology of rising incidence in generations born since 1950 and increasing access to high-quality screening and treatment among all populations, especially Native Americans.     

Molecular subtypes of colorectal cancers determined by PCR‐based analysis

Tumor tissue consists of a heterogeneous cell population. The allelic imbalance (AI) ratio, determined in isolated tumor glands, is a good index of tumor heterogeneity. However, associations of the patterns of AI and microsatellite instability (MSI) development, observed in most cases of colorectal cancer (CRC), with tumor progression have not been reported previously. In this study, we examined whether CRC genetic profiles stratified by a combination of the AI ratio and MSI facilitate categorization of CRC, and whether these genetic profiles are associated with specific molecular alterations in CRC. A crypt isolation method was used to isolate DNA from tumors and normal glands obtained from 147 sporadic CRCs. AI and MSI statuses were determined using PCR‐based microsatellite analysis and stratified based on AI ratio and MSI status. DNA methylation status (high methylation, intermediate methylation and low methylation status and mutations in KRAS, BRAF, and TP53 were examined. In addition, mucin markers were immunostained. Based on this analysis, four subgroups were categorized. Subgroup 1 was characterized by a high MSI status and BRAF mutation; subgroup 2 was closely associated with a high AI ratio, which accumulated during the early phases of colorectal carcinogenesis, and TP53 mutation; subgroup 3 was associated with a low AI ratio, seen during the later phases of colorectal carcinogenesis, and KRAS mutation; and subgroup 4 was defined as a minor subgroup. These results confirmed that classification of distinct molecular profiles provides important insights into colorectal carcinogenesis.