Colonoscopic surveillance of first-degree relatives of colorectal cancer patients in a faecal occult blood screening programme

Background: In some Italian areas, colonoscopic surveillance of first-degree relatives (FDRs) of colorectal cancer (CRC) patients is provided as a part of local population-based faecal occult blood test (FOBT) screening programmes. The objective of the present study was to assess the feasibility and early results of this surveillance model. Methods: Data from district screening centres were used to evaluate the process of identification and selection of eligible FDRs (residence in the Emilia-Romagna Region, age 40–75 years, no recent colonoscopy) of screen-detected CRC patients and the detected prevalence of disease. The probability for an FDR to undergo colonoscopy and to be diagnosed with CRC and advanced adenoma was estimated using the Kaplan–Meier method. The sex- and age-standardised ratio of detected prevalence to that expected based on results from a colonoscopy screening study of the Italian general population was estimated. Results: Between 2005 and 2011, 9319 FDRs of 2437 screen-detected CRC patients (3.8 per patient) were identified and contacted. Their likelihood of being eligible for, and accepting, colonoscopy was 0.11 (95% confidence interval: 0.11–0.12). Among the 926 subjects undergoing colonoscopy, the prevalence of previous negative screening FOBT was 63%. Eleven CRCs (1.2%) and 100 advanced adenomas (10.8%) were detected. The standardised ratio of detected prevalence to that expected was 0.91 (95% confidence interval: 0.19–2.66) for CRC and 1.48 (1.04–2.05) for advanced adenoma. Conclusions: The procedure of selection of FDRs was extremely ineffective. Due to previous negative screening tests, the prevalence of disease was less than expected. A population-based FOBT screening programme is a highly unsuitable setting for the provision of surveillance to FDRs of CRC patients.     

The impact of driving time on participation in colorectal cancer screening with sigmoidoscopy and faecal immunochemical blood test

BackgroundHigh participation rates are important for a colorectal cancer (CRC) screening programme to be effective. Having a long travelling distance to screening centres may impede participation.MethodsWe analysed the association between driving time from home address to screening centre and participation among individuals invited to screening with faecal immunochemical test (FIT) (n = 68,624) or sigmoidoscopy (n = 46,076) in a randomized trial in Norway in 2012–17. Two screening centres were involved. We fitted multiple logistic regression models, adjusted for demographic, socioeconomic and health characteristics, and reported odds ratios (OR) with 95% confidence intervals (CI).ResultsParticipation rates were 58.9 % (n = 40,445) for FIT and 51.9 % (n = 23,911) for sigmoidoscopy. In sigmoidoscopy, participation was 56.9 % and 47.9 % in those living < 20 and > 60 min by car from the screening centres, respectively. For each 10 min driving time increase, OR for participating in sigmoidoscopy screening was 0.93 (95 % CI 0.91–0.95). There was a significant difference between the two screening centres (p-value for heterogeneity <0.001). Participation in FIT screening were 61.2 % and 57.1 % in those with < 20 and > 60 min driving time, respectively, and the OR was 0.98 (95 % CI 0.96–0.99) for each 10 min increase (heterogeneity between screening methods, P-value <0.001). Among those with a positive FIT, compliance to colonoscopy was higher in those living < 20 compared to > 60 min from the centres (95.1 % vs. 92.9 %, respectively, OR 0.86; 95 % CI 0.77–0.93 for each 10 min increase).ConclusionsDriving time to screening centre was a significant predictor of participation, mainly in sigmoidoscopy. There were local differences in the impact of driving time on participation. Driving time also affected compliance to colonoscopy after a positive FIT. When planning a CRC screening programme, one should consider offering people living far from screening sites special assistance to facilitate their participation.     

Lessons learnt from the implementation of a colorectal cancer screening programme for lynch syndrome in a tertiary public hospital

BackgroundLynch syndrome (LS) is the first cause of inherited colorectal cancer (CRC), being responsible for 2–4% of all diagnoses. Identification of affected individuals is important as they have an increased lifetime risk of multiple CRC and other neoplasms, however, LS is consistently underdiagnosed at the population level. We aimed to evaluate the yield of LS screening in CRC in a single-referral centre and to identify the barriers to its effective implementation.MethodsLS screening programme included individuals with CRC < 70 years, multiple CRC, or endometrial cancer at any age. Mismatch repair (MMR) protein immunohistochemistry (IHC) analysis was performed in routine practice on the surgical specimen and, if MLH1 IHC was altered, MLH1 gene promoter methylation was analysed. Results were collected in the CRC multidisciplinary board database. LS suspected individuals (altered MMR IHC without MLH1 promoter methylation) were referred to the Cancer Genetic Counselling Unit (CGCU). If accepted, a genetic study was performed. Two checkpoints were included: review of the pathology data and verification of patient referral by a genetic counsellor.ResultsBetween 2016 and 2019, 381 individuals were included. MMR IHC analysis was performed in 374/381 (98.2 %) CRC cases and MLH1 promoter methylation in 18/21 (85.7 %). Seventeen of the 20 LS suspected individuals were invited for referral at the CGCU. Two cases were not invited and the remaining patient died of cancer before completion of tumour screening. Fifteen individuals attended and a genetic analysis was performed in 15/20 (75 %) LS suspected individuals. Ten individuals were diagnosed with LS, in concordance with the IHC profile (2.7 % of the total cohort). This led to cascade testing in 58/75 (77.3 %) of the available adult relatives at risk, identifying 26 individuals with LS.ConclusionsEstablishing a standardized institutional LS screening programme with checkpoints in the workflow is key to increasing the yield of LS identification.     

Effectiveness of population-based colorectal cancer screening programme in down-staging

BackgroundThis is the first evaluation study to assess the demographic characteristics of the colorectal cancer (CRC) cases detected in the prevalent round of the population-based Colorectal Cancer Screening Programme (CRCSP) in Hong Kong and to explore the effectiveness of the programme on the stage distribution of CRC.MethodsThis study covered the period between 28 September 2016 and 31 December 2018. Information on CRC diagnosis, age and stage at diagnosis were retrieved and reviewed by the Hong Kong Cancer Registry (HKCaR). The CRC detection rate among CRCSP-screened participants and incidence rate among the Hong Kong general population were calculated respectively. The odds ratio (OR) was calculated to measure the strength of association and quantify the effect of CRCSP on stage shift between CRCSP-detected CRC cases and an age-matched cohort of CRC cases diagnosed outside the programme.ResultsThe CRC detection rate among participants of the CRCSP during the study period was 736.0/100,000, whereas the overall CRC incidence rate among general population of similar age groups was 393.7/100,000. For all ages and both sexes, the OR of stage I CRCSP-detected CRC compared to the CRC from the age-matched cohort was 3.91 (95%CI=3.41–4.48) and the OR dropped to 0.54 (95%CI=0.41–0.70) at stage IV. Meanwhile, the overall OR of CRCSP-detected CRC compared to CRC from the age-matched cohort dropped from 2.24 (95%CI=1.97–2.56) to 1.62 (95%CI=1.40–1.87) with increasing age.ConclusionThe present study has demonstrated the initial impact of the CRCSP on shifting the stage at diagnosis towards earlier stage. The benefit of stage-shift was similar for all ages from 60 to 77 in both sexes and seems to increase with younger age. Given the stage-dependent survival outcomes, this stage-shift could lead to a reduction in CRC-associated mortality in Hong Kong in future.     

Rates and outcomes of testing for lynch syndrome in a national colorectal cancer screening programme

BackgroundLynch Syndrome (LS), the most common cause of hereditary colorectal cancer (CRC), is characterised by pathogenic variants in mismatch repair (MMR) genes. Universal testing of all CRCs for LS can increase detection. Rates and outcomes of testing in Ireland’s national CRC screening programme have not been examined previously.MethodsCRCs diagnosed at two screening sites between 2015 and 2020 were identified. Patient records were used to determine if CRCs had been tested for MMR deficiency and if detected, what downstream testing to rule out LS or genetic testing to confirm LS was undertaken.ResultsOver five years, 206 CRCs were diagnosed. Testing for LS was carried out for 100% of CRCs at site A and 69% of CRCs at site B. Of CRCs tested for LS, 14 (8%) were MMR deficient. After downstream testing for BRAF mutation or hypermethylation of MLH1, three CRCs were identified as potentially LS-related. Of these two individuals declined genetic testing and one was lost to follow-up.ConclusionsBy 2020 both sites had implemented universal testing of all CRCs for LS. A small number of individuals were identified as being eligible for genetic testing for LS, however those offered declined testing and one individual was lost to follow up. This highlights the importance of universal testing and the need for referral pathways to ensure all appropriate individuals are referred onwards to genetic services.     

Stool DNA test targeting methylated syndecan-2 (SDC2) as a noninvasive screening method for colorectal cancer

Despite the steadily increasing worldwide incidence of colorectal cancer (CRC), an effective noninvasive approach for early detection of CRC is still under investigation. The guaiac-based fecal occult blood test (FOBT) and fecal immunochemical test (FIT) have gained popularity as noninvasive CRC screening tests owing to their convenience and relatively low costs. However, the FOBT and FIT have limited sensitivity and specificity. To develop a noninvasive tool for the detection of CRC, we investigated the sensitivity, specificity, and accuracy of a stool DNA test targeting methylated syndecan-2 (SDC2), which is frequently methylated in patients with CRC. The present study enrolled 62 patients diagnosed as having stage 0-IV CRC and 76 healthy participants between July 2018 and June 2019 from two institutions. Approximately 4.5 g of stool sample was collected from each participant for detection of human methylated SDC2 gene. In total, 48 of 62 (77.4%) patients with CRC showed positive results, whereas 67 out of 76 (88.2%) healthy participants showed negative results. The area under the curve of the receiver operating characteristic curve constructed was 0.872 for discrimination between patients with CRC and healthy individuals. The present study highlights the potential of the fecal methylated SDC2 test as a noninvasive detection method for CRC screening with a relatively favorable sensitivity of 77.4%, a specificity of 88.2% and a positive predictive value of 84.2% compared with other available fecal tests. Further multicenter clinical trials comprising subjects of varied ethnicities are required to validate this test for the mass screening of patients with CRC.     

Progress in the identification of plasma biomarkers of colorectal cancer

Proteomic analysis of human tissue and plasma samples has been a useful tool in recent years for the identification of potential biomarkers to aid in the early diagnosis of colorectal cancer. However, biomarkers relating to the crucial transition between adenomatous lesions and invasive colorectal malignancy have not previously been described. The work of Choi et al. (Proteomics 2013, 13, 2361–2374) attempts to address this issue. Using plasma samples from age‐matched patients with colorectal adenomas or invasive disease this group identified a range of plasma proteins and cytokines that were differentially expressed. This information not only provides insights into the biology of the adenoma to carcinoma progression sequence but it also represents a step towards the goal of achieving diagnostically accurate and clinically acceptable biomarkers in early colorectal cancer.     

Subsite- and stage-specific colorectal cancer trends in Estonia prior to implementation of screening

BackgroundThe occurrence of colorectal cancer (CRC) in Estonia has been characterised by increasing incidence, low survival and no screening. The study aimed to examine long-term incidence and survival trends of CRC in Estonia with specific focus on subsite and stage.MethodsWe analysed CRC incidence and relative survival using Estonian Cancer Registry data on all cases of colorectal cancer (ICD-10 C18–21) diagnosed in 1995–2014. TNM classification was used to categorise stage.ResultsAge-standardized incidence of colon cancer increased both in men and women at a rate of approximately 1% per year. Significant increase was seen for right-sided tumours, but not for left-sided tumours. Rectal cancer incidence increased significantly only in men and anal cancer incidence only in women. Age-standardized five-year relative survival for colon cancer increased from 50% in 1995–1999 to 59% in 2010–2014; for rectal cancer, from 38% to 56%. Colon cancer survival improved significantly for left-sided tumours (from 51% to 62%) and stage IV disease (from 6% to 15%). For rectal cancer, significant survival gain was seen for stage II (from 58% to 75%), stage III (from 34% to 70%) and stage IV (from 1% to 12%).ConclusionIn the pre-screening era in Estonia, increase in colon cancer incidence was limited to right-sided tumours. Large stage-specific survival gain, particularly for rectal cancer, was probably due to better staging and advances in multimodality treatment. Nonetheless, more than one quarter of new CRC cases are diagnosed at stage IV, emphasising the need for an efficient screening program.     

Mutational spectrum of BRAF gene in colorectal cancer patients in Saudi Arabia

Colorectal cancer (CRC) is one of the topmost causes of death in males in Saudi Arabia. In females, it was also within the top five cancer types. CRC is heterogeneous in terms of pathogenicity and molecular genetic pathways. It is very important to determine the genetic causes of CRC in the Saudi population. BRAF is one of the major genes involved in cancers, it participates in transmitting chemical signals from outside the cells into the nucleus of the cells and it is also shown to participate in cell growth. In this study, we mapped the spectrum of BRAF mutations in 100 Saudi patients with CRC. We collected tissue samples from colorectal cancer patients, sequenced the BRAF gene to identify gene alterations, and analyzed the data using different bioinformatics tools. We designed a three-dimensional (3D) homology model of the BRAF protein using the Swiss Model automated homology modeling platform to study the structural impact of these mutations using the Missense3D algorithm. We found six mutations in 14 patients with CRC. Four of these mutations are being reported for the first time. The novel frameshift mutations observed in CRC patients, such as c.1758delA (E586E), c.1826insT (Q609L), c.1860insA and c.1860insA/C (M620I), led to truncated proteins of 589, 610, and 629 amino acids, respectively, and potentially affected the structure and the normal functions of BRAF. These findings provide insights into the molecular etiology of CRC in general and to the Saudi population. BRAF genetic testing may also guide treatment modalities, and the treatment may be optimized based on personalized gene variations.     

Application of fast track surgery in routine nursing for patient with colorectal cancer

Objective: To investigate the clinical effect of fast track surgery (FTS) in perioperative nursing of colorectal cancer surgery. Background: In recent years, many complicated surgery began to develop in the direction of low invasion and short hospital time, which provides an unprecedented opportunity for the development of fast track surgery (FTS). Methods: According to different nursing measures, 156 cases of colorectal cancer patients treated in our hospital were divided into FTS nursing group (86 cases) and traditional nursing group (70 cases). FTS nursing care and traditional nursing care were respectively employed to analyze and compare postoperative recovery and complications of the two groups. Results: FTS nursing group was significantly shorter than the traditional care group in terms of the first postoperative exhaust time, the first defecation time, the first eating time, ambulation time and postoperative hospital time, with statistical significance (P < .05); compared with the conventional nursing group, FTS group significantly had lower incidence of postoperative intestinal obstruction, lower limb vein thrombus formation and gastrointestinal discomfort, with statistical significance (P < .05); FTS group has less situations of nausea and vomiting, incision infection, pulmonary infection, urinary tract infection and anastomotic leakage compared to the conventional nursing group. Conclusion: FTS nursing can effectively promote the postoperative recovery of intestinal function for patients with colorectal cancer and reduce the occurrence of postoperative complications, which will relieve postoperative pain and shorten the length of stay, giving patients increased rehabilitation quality.     

Defining a mutational signature for endometrial cancer screening and early detection

IntroductionThe current availability of genomic information represents an opportunity to develop new strategies for early detection of cancer. New molecular tests for endometrial cancer may improve performance and failure rates of histological aspirate-based diagnosis, and provide promising perspectives for a potential screening scenario. However, the selection of relevant biomarkers to develop efficient strategies can be a challenge.Materials and methodsWe developed an algorithm to identify the largest number of patients with endometrial cancer using the minimum number of somatic mutations based on The Cancer Genome Atlas (TCGA) dataset.ResultsThe algorithm provided the number of subjects with mutations (sensitivity) for a given number of biomarkers included in the signature. For instance, by evaluating the 50 most representative point mutations, up to 81.9% of endometrial cancers can be identified in the TCGA dataset. At gene level, a 92.9% sensitivity can be obtained by interrogating five genes.DiscussionWe developed a computational method to aid in the selection of relevant genomic biomarkers in endometrial cancer that can be adapted to other cancer types or diseases.     

LDCT lung cancer screening eligibility and use of CT scans for lung cancer among sexual minorities

ObjectiveTo compare eligibility for lung cancer screening and receipt of a CT scan for lung cancer among sexual minorities.MethodsSecondary data analysis of cross-sectional data from older U.S. adults in the Behavioral Risk Factor Surveillance System survey during the 2017 cycle (n = 20,685).ResultsRates of eligibility for low-dose helical computed tomography (LDCT) were roughly twice as high among sexual minorities than among heterosexuals (21.1% vs. 11.7%). The odds of gay men and lesbian women indicating eligibility for LDCT screening were four to five times higher when compared to their heterosexual peers. No statistically significant differences were found between sexual minorities and heterosexuals with respect to having a CT scan for lung cancer in the past year.ConclusionsThere are potential sexual-identity-related disparities in the utilization of lung cancer screening among eligible smokers. Interventions are needed to increase awareness and uptake of lung cancer screening in order to detect and manage this common form of cancer in the U.S.     

Enhanced expression of the complement regulatory protein CD55 predicts a poor prognosis in colorectal cancer patients

This study prospectively correlated the level of expression of CD55 on tumours with 7-year survival in 136 colorectal cancer patients. Patients with tumours expressing high levels of CD55 had a significantly worse survival (24%) than patients with low CD55 levels (50%, p<0.02). A similar difference was seen for patients (Duke's B or C) with a high risk of recurrence (29% vs 58%, p<0.05). Furthermore, there was a progressive deterioration in prognosis with increasing antigen expression (p=0.01). It remains unclear if CD55 is overexpressed by tumours to protect them from complement or if it is related to the recent observation that CD55 is a ligand for the T-cell activation antigen CD97. However, it is a marker of aggression, as colorectal cancer patients whose tumours overexpress CD55 have a significantly reduced 7-year survival.     

Initial screening of gastric cancer using oral contrast-enhanced trans-abdominal ultrasonography in rural asymptomatic individuals

Background & aimsInitial screening for high-risk population of gastric cancer (GC) is needed in rural areas of large-population countries. This study aims to explore the feasibility of applying noninvasive ultrasonography as an initial screening strategy to improve the early diagnosis and prevention of GC.MethodsOral contrast-enhanced trans-abdominal ultrasonography (OCTU) was initially applied to screen around 15,000 residents from 24 different rural villages of Changxing Island in Shanghai, China, facilitating the identification of high-risk population for further endoscopy examination.Results176 subjects (1.18 %) were initially identified with gastric diseases using OCTU while 14,787 ones (98.93 %) were normal with negative results. 145 out of 176 individuals (82.39 %) took further endoscopy examination, and 16 were diagnosed with GC with biopsy examination, with 9 of them at the early stage. We followed up with the Center for Disease Control and Prevention, and identified another 6 GC cases occurred within one year among OCTU-negative population, serving as an adjustment factor for sensitivity analysis. As a result, with a total of 22 GC cases included in this cohort, the positive predictive rate, the negative predictive value, sensitivity, and specificity were 9.09％, 99.96 %, 75.5 %, and 98.93 %, respectively.ConclusionsOCTU is feasible, non-invasive, low-cost, and widely acceptable in rural area, thus we proposed that OCTU is practicable to serve as a supplementary screening method to improve the early detection of GC in rural area of China and other developing countries with large population.     

薄层液基细胞学在宫颈癌及其癌前病变筛查中的价值

目的：评价薄层液基细胞学（Thin prep cytology test,TcT）检测技术对宫颈癌前病变的诊断和宫颈癌筛查的准确性及临床价值。方法：收集分析2009年5月～2010年11月在我院妇科门诊行TCT检查的受检者7340例,以细胞学诊断为未明确意义的不典型鳞状上皮细胞（ASC—US）及以上者为阳性结果,并对阳性结果行病理组织学诊断,以组织学诊断作为金标准、,结果：液基细胞学标本满意度高,对SCC、HSIL、LSIL的准确率分别为76．8％、97.3％、100％。结论：TCT结合TBS诊断系统是目前诊断宫颈癌前病变和筛查宫颈癌的理想方法川,同时也可以作为一项宫颈癌术后随访的检测指标。ASC—US患者中存在部分年轻的高危癌前病变者。     

结直肠癌与肠道微生物群研究进展

肠道微生物群是人体内环境的重要组成部分,与宿主共进化、共代谢、共发育,并与宿主之间相互调控,影响宿主健康。近年研究显示,肠道微生物群参与了结直肠癌的发生和发展。了解肠道微生物群的特征性变化及其诱发结直肠癌的机制对于结直肠癌的防治有着重要意义。目前以肠道微生物群为靶点的干预性基础研究也取得了一些突破性的研究进展。本文主要对结直肠癌患者肠道微生物群的变化、其可能的致病机制及临床相关研究进展等进行综述。     

Racial differences in colorectal cancer survival at a safety net hospital

BackgroundWhile racial disparity in colorectal cancer survival have previously been studied, whether this disparity exists in patients with metastatic colorectal cancer receiving care at safety net hospitals (and therefore of similar socioeconomic status) is poorly understood.MethodsWe examined racial differences in survival in a cohort of patients with stage IV colorectal cancer treated at the largest safety net hospital in the New England region, which serves a population with a majority (65%) of non-Caucasian patients. Data was extracted from the hospital’s electronic medical record. Survival differences among different racial and ethnic groups were examined graphically using Kaplan-Meier analysis. A univariate cox proportional hazards model and a multivariable adjusted model were generated.ResultsBlack patients had significantly lower overall survival compared to White patients, with median overall survival of 1.9 years and 2.5 years respectively. In a multivariate analysis, Black race posed a significant hazard (HR 1.70, CI 1.01–2.90, p = 0.0467) for death. Though response to therapy emerged as a strong predictor of survival (HR = 0.4, CI = 0.2-0.7, p = 0.0021), it was comparable between Blacks and Whites.ConclusionsDespite presumed equal access to healthcare and socioeconomic status within a safety-net hospital system, our results reinforce findings from previous studies showing lower colorectal cancer survival in Black patients, and also point to the importance of investigating other factors such as genetic and pathologic differences.