Mutation Analysis of the APC Gene in a Chinese FAP Pedigree with Unusual Phenotype

Background and Aim. Germline mutations of the adenomatous polyposis coli (APC) gene cause familial adenomatous polyposis (FAP), an autosomal dominant inherited disease mainly characterized by colorectal adenomatous polyposis. Genetic studies of FAP have shown that somatic APC mutations are dependent on the position of the germline APC mutation. However, the molecular mechanism underlying these genotype-phenotype associations for APC in Chinese remain largely unknown. Patients and Methods. In this study, we investigated the APC gene mutation in a Chinese FAP family by systematic screening with multiplex ligation-dependent probe amplification (MLPA), denaturing high-performance liquid chromatography (dHPLC), and DNA sequencing. Promoter methylation was detected by methylation-specific PCR. Results. The identical germline mutation c.1999 C>T (Q667X) of APC was identified in 5 affected members, among which 2 members carried somatic mutations of APC, one with promoter hypermethylation and the other with loss of wild-type allele in their adenomas. The somatic mutations were shown connected with the disease severity, demonstrating a unique genotype-phenotype association in this FAP pedigree. Conclusion. The study revealed the existence of novel pathogenic mutations in Chinese patients with FAP. Somatic mutations are of particular interest because of the unusual phenotypic features shown by patients

Colonic polyps: inheritance, susceptibility, risk evaluation, and diagnostic management

Colorectal cancer (CRC) is the third-ranked neoplasm in order of incidence and mortality, worldwide, and the second cause of cancer death in industrialized countries. One of the most important environmental risk factors for CRC is a Western-type diet, which is characterized by a low-fiber and high-fat content. Up to 25% of patients with CRC have a family history for CRC, and a fraction of these patients are affected by hereditary syndromes, such as familial adenomatous polyposis, Gardner or Turcot syndromes, or hereditary nonpolyposis colorectal cancer. The onset of CRC is triggered by a well-defined combination of genetic alterations, which form the bases of the adenoma-carcinoma sequence hypothesis and justify the set-up of CRC screening techniques. Several screening and diagnostic tests for CRC are illustrated, including rectosigmoidoscopy, optical colonoscopy (OC), double contrast barium enema (DCBE), and computed tomography colonography (CTC). The strengths and weaknesses of each technique are discussed. Particular attention is paid to CTC, which has evolved from an experimental technique to an accurate and mature diagnostic approach, and gained wide acceptance and clinical validation for CRC screening. This success of CTC is due mainly to its ability to provide cross-sectional analytical images of the entire colon and secondarily detect extracolonic findings, with minimal invasiveness and lower cost than OC, and with greater detail and diagnostic accuracy than DCBE. Moreover, especially with the advent and widespread availability of modern multidetector CT scanners, excellent quality 2D and 3D reconstructions of the large bowel can be obtained routinely with a relatively low radiation dose. Computer-aided detection systems have also been developed to assist radiologists in reading CTC examinations, improving overall diagnostic accuracy and potentially speeding up the clinical workflow of CTC image interpretation

Colonoscopy quality assessment in a mass population screening programme based on faecal occult blood test

Background and aim: the success of colorectal cancer (CRC) screening programmes largely depends on the quality of the events, processes and outcomes and therefore, quality assurance of endoscopy is an essential component. The quality indicators for colonoscopy in a screening programme setting are different from those performed in symptomatic people. The objective of this study was to report the main quality indicators of colonoscopies performed after a positive faecal occult blood test (FOBT) in a CRC screening programme in Catalonia. Methods: the period of study includes three rounds of the CRC screening programme from June 2006 to July 2013. Two types of FOBT were used: a qualitative biochemical guaiac-based test (gFOBT) and a quantitative immunochemical test (FIT). Quality indicators analysed in this study were compared to recommended colonoscopy standards from the published guidelines. Results: during the study period, 1,806 colonoscopies were performed in 1,691 individuals with a positive FOBT. All indicators were within the standard except waiting time to colonoscopy. Caecal intubation rate was 95.6 % and adequate bowel cleansing 93.6 %. Adenoma detection rate was better using FIT than gFOBT, 30.7 and 3.8 per 1,000 screenees, respectively. Cancer detection rate was also greater using FIT. Nearly 62 % of cancers were diagnosed at an early stage. The overall complication rate was 10.7 . Conclusion: although the majority of results reached the recommended standards, some areas have been identified for quality enhancement. Continuous monitoring of quality indicators is essential for improving the current effectiveness of CRC screening programmes

Clinicians’ Guide to Artificial Intelligence in Colon Capsule Endoscopy—Technology Made Simple

Artificial intelligence (AI) applications have become widely popular across the healthcare ecosystem. Colon capsule endoscopy (CCE) was adopted in the NHS England pilot project following the recent COVID pandemic’s impact. It demonstrated its capability to relieve the national backlog in endoscopy. As a result, AI-assisted colon capsule video analysis has become gastroenterology’s most active research area. However, with rapid AI advances, mastering these complex machine learning concepts remains challenging for healthcare professionals. This forms a barrier for clinicians to take on this new technology and embrace the new era of big data. This paper aims to bridge the knowledge gap between the current CCE system and the future, fully integrated AI system. The primary focus is on simplifying the technical terms and concepts in machine learning. This will hopefully address the general “fear of the unknown in AI” by helping healthcare professionals understand the basic principle of machine learning in capsule endoscopy and apply this knowledge in their future interactions and adaptation to AI technology. It also summarises the evidence of AI in CCE and its impact on diagnostic pathways. Finally, it discusses the unintended consequences of using AI, ethical challenges, potential flaws, and bias within clinical settings

Volume 07, issue 4

The mission of CJS is to contribute to the effective continuing medical education of Canadian surgical specialists, using innovative techniques when feasible, and to provide surgeons with an effective vehicle for the dissemination of observations in the areas of clinical and basic science research. Visit the journal website at http://canjsurg.ca/ for more.https://ir.lib.uwo.ca/cjs/1071/thumbnail.jp

Examining Change Over Time in the Association Between Healthcare Access on Disparities in Colorectal Cancer Mortality for Minorities as Compared to Whites.

INTRODUCTION: Several studies have looked at the various factors that could explain the disparity in cancer diagnosis outcome including that for colorectal cancer between minorities and Whites. Studies have also shown that when it comes to insurance status Blacks and Hispanics are more likely to have higher uninsured rates. 3,1 With the implementation of the Affordable Care Act (ACA) in 2010 there has been a decline in the uninsured rate, with the rate of decline differing by state. AIM: This thesis examines whether the observed decline in CRC mortality rates observed nationally was comparable for minorities and whites in the 25 states with data for both groups. The questions that will guide the thesis: 1)What association can be found between the expanded health care coverage for colorectal cancer screening following the ACA (2010) and colorectal cancer mortality? Does the disparity pattern in CRC mortality for minorities as compared to whites change after 2010? METHODS: This thesis uses state-level secondary data on colorectal cancer mortality from the period of 1990 to 2013 for 25 states in the United States which had data for White, Black and Hispanic populations. Data were provided each year by the National Vital Statistics System at the National Center for Health Statistics of the Centers for Disease Control and Prevention and the National Cancer Institute\u27s Surveillance, Epidemiology, and End Results (SEER) Program. Access to care as measured by the uninsured rate for the 25 states derives from various sources and was not available for each year. Two time periods were identified (early and later period) and mean mortality and insurance rates were calculated over these two intervals. Regression analysis was performed on the two-time intervals of data stacked over two periods (early and later periods), with a binary time indicator variable to differentiate the early and late periods. The regression included the CRC mortality rate for whites and the CRC mortality rates for Blacks and Hispanics for each state in each period (4 observations per state) as the dependent variable, a total of 100 observations. Regressors included the uninsured rate for all populations in each time interval for each state (2 unique observations per state), an indicator of minority versus white race/ethnicity (50 observations=1, rest=0), and a time indicator (later time=1, earlier=0). The time and minority indicators were interacted to test whether minority CRC mortality rates fell after 2010 as compared to Whites, holding constant access to care (insurance status), the overall trend in CRC mortality, and the overall minority effect associated with CRC. Defining the time intervals as periods pre- and post- 2010, the main hypothesis was to assess whether these CRC mortality outcomes changed significantly pre-post the 2010 implementation of the ACA, and whether there were differential effects over time for minorities versus whites. RESULTS: Over both periods together, a higher state uninsured rate was associated with a higher state CRC mortality rate, but this was not statistically significant (p = 0.294). Over both periods together, the CRC mortality rate for Hispanics and Blacks was higher than that for whites, by 7.94 deaths per 100,000, and this was statistically significant. There was a reduction in the average CRC mortality rate by 4.73 deaths per 100,000 over the time periods for everybody, and this was statistically significant (p = 0.000). However, in the later period, the Black and Hispanic CRC mortality rate fell by an additional 2.073 deaths per 100,000 as compared to the overall decline and this was significant (p = 0.035). Thus, there was a larger decline in the CRC mortality rate for Blacks and Hispanics compared to whites over the two periods, which suggests that the passage of the ACA may have reduced disparities in CRC mortality among minorities as compared to whites. DISCUSSION: Over the twenty-four-year period from 1990 to 2013, there was a steady decline in the CRC mortality rate for Blacks, Hispanics, and Whites. This thesis shows that the decline in mortality rate is weakly associated with a decline in uninsured rate, when comparing the average rates for both in 2009 and 2013, and not adjusting statistically for other factors. However, the association between the uninsured rate and CRC mortality rate by race/ethnicity group remains unknown, because data on uninsured by each group was not available for all 25 states in the two-time periods pre- and post- 2010. Also, not known is whether there was a change over time in the association between a state’s uninsured rates and the CRC mortality rates, which we could have ascertained using another time interaction with uninsured rates had these been available by group. Holding overall uninsured rate constant statistically in the model was necessary to disentangle the reduction in the minority CRC mortality rate as compared to Whites by the later period. Failure to hold uninsured rates constant statistically could have resulted in omitted variables bias on the minority effects, assuming that minority uninsured rates differed from whites. Future analyses should attempt to determine what if any insurance effects were present for the different groups. A three-way interaction between uninsured by group and time could also determine whether the insurance effects were stronger for one group than for another, which would have interesting policy implications

A PROGRAM EVALUATION OF A COLON CANCER SCREENING PROGRAM USING AT-HOME FECAL IMMUNOCHEMICAL TESTS WITH CERTIFIED PATIENT NAVIGATORS

Colorectal cancer is the second leading cause of cancer-related death in this country, but 33% of these deaths could be prevented by screening. While colonoscopy is an effective screening tool, it is expensive, invasive, and prone to encounter considerable patient resistance. An alternative is to first screen those at-risk using at-home fecal immunochemical test (FIT) kits. This study determined factors associated with the return of these kits distributed by Kentucky CancerLink, a non-profit organization, and its affiliates to participants in a colon cancer prevention program. Objectives: To identify factors associated with: completing a FIT kit, completing the kit with minimal prompting, a positive FIT kit result, and a positive colonoscopy result. To evaluate a colon cancer screening program for internal and Commission on Cancer (CoC) implementation goals: ship kits promptly; notify patients and their physician, if requested, of FIT results promptly; follow-up on positive FIT results; encourage a high percentage of patients with a positive FIT to complete physician recommended follow-up; and evaluate effectiveness of follow-up contact policy. Design: Descriptive Setting: Non-profit organization in central Kentucky Participants: The study analyzed data collected on 436 FIT kit participants, and 17 direct to colonoscopy participants, during the period January 1 through October 30, 2016. Participants were eligible if over 45 and African American or over 50 for all other races or family history of early-onset colon cancer or precancerous condition, Kentucky resident, and no history of colonoscopy in the past 5 years. Outcome measures: FIT kit return, return of the FIT kit with 0-2 follow-up calls, FIT kit result, colonoscopy result, percentage of FIT kits shipped to participants in 0-2 business days, percentage of patients notified of FIT results in 0-2 business days, percentage of physicians notified in 0-2 business days, percentage of patients with positive FIT followed, percentage of patients with positive FIT who completed follow-up, number of calls and last attempt letters. Results: Participants over 60 years of age had higher return rates than those under 60. Participants recruited via advertising, physician referrals, or health fairs had better return rates than participants recruited via church, work, or cold calls. Men were more likely than women to promptly return their kits. Caucasian: non- Hispanics were more likely to have a positive FIT result than African American or Hispanic & Other ethnicities. Participants referred by physician cold call list or advertising were more likely to have a positive FIT than those recruited via physician referrals, health fairs, church, or work. Participants directly referred to colonoscopy were more likely to have a positive finding on colonoscopy than those who had a positive FIT kit. The program met its goals statistically of shipping kits promptly and following up on positive FIT results. A policy of 3 follow-up calls and a last attempt letter was successful in encouraging the majority of participants to complete their kits. Conclusions: While this study involved a relatively small sample size and cannot be generalized to a larger population, the value of evaluating a screening program, learning which methods of recruitment bear more fruit than others, and using that information can be generalized to other organizations, no matter the size of the program. Patient navigators encouraged 73.62% of participants to complete their FIT kits through the use of follow-up calls and last attempt letters. Adults at greater risk of colon cancer responded well to the program. Adults over 60 were more likely to complete their kit. Men were more likely to complete their kit with minimal prompting. Patients who were screened directly to colonoscopy were more likely to have positive colonoscopy result. The program met its internal and CoC guidelines. These findings inform public health officials on how to allocate resources to maximize return of FIT kits in a colon cancer prevention program. Future programs would do well to recognize that participants themselves were still the rate limiting step, so patient navigators should put the kits in the hands of at risk people, and remind them

Current Status and Emerging Trends in Colorectal Cancer Screening and Diagnostics

Colorectal cancer (CRC) is a prevalent and potentially fatal disease categorized based on its high incidences and mortality rates, which raised the need for effective diagnostic strategies for the early detection and management of CRC. While there are several conventional cancer diagnostics available, they have certain limitations that hinder their effectiveness. Significant research efforts are currently being dedicated to elucidating novel methodologies that aim at comprehending the intricate molecular mechanism that underlies CRC. Recently, microfluidic diagnostics have emerged as a pivotal solution, offering non-invasive approaches to real-time monitoring of disease progression and treatment response. Microfluidic devices enable the integration of multiple sample preparation steps into a single platform, which speeds up processing and improves sensitivity. Such advancements in diagnostic technologies hold immense promise for revolutionizing the field of CRC diagnosis and enabling efficient detection and monitoring strategies. This article elucidates several of the latest developments in microfluidic technology for CRC diagnostics. In addition to the advancements in microfluidic technology for CRC diagnostics, the integration of artificial intelligence (AI) holds great promise for further enhancing diagnostic capabilities. Advancements in microfluidic systems and AI-driven approaches can revolutionize colorectal cancer diagnostics, offering accurate, efficient, and personalized strategies to improve patient outcomes and transform cancer management

Post-polypectomy surveillance colonoscopy: In whom and when?

Introduction Post-polypectomy surveillance by colonoscopy is recommended in national and international guidelines. While colonoscopy is the gold standard colorectal investigation, it carries a risk of adverse events as well as being inconvenient and often uncomfortable for the patient. It is established that population screening reduces mortality from colorectal cancer (CRC). The effect of post-polypectomy surveillance, however, is less clear. An increasing number of colonoscopies are being performed worldwide for both symptoms and screening. The adenoma detection rate at colonoscopy is also increasing with improved technology and training against the backdrop of an ageing population. As a result, an increasing number of individuals are entering post-polypectomy surveillance. Aims & Objectives The aim of the analysis was to evaluate the findings of post-polypectomy surveillance within the English Bowel Cancer Screening Programme (BCSP). This was done by assessing linked data from the BCSP database and the National Cancer Registration and Analysis Service (NCRAS). Objectives were: 1. To document surveillance pathways among the intermediate and high risk groups. 2. To determine the risk factors (adenoma and person-specific) at screening which predict the outcome of initial surveillance. 3. To determine the adenoma, advanced adenoma (AA) and CRC yield at initial surveillance of each colonoscopy surveillance cohort (and subcategories within each cohort) within the BCSP. Methods Data on individuals participating in the BCSP is entered prospectively onto the screening programme’s relational database, BCSS. BCSS was interrogated for individuals who had attended for post-polypectomy surveillance at any time from the start of the programme in 2006 until the end of 2016. In addition, linked data on CRCs diagnosed in this cohort were obtained from NCRAS. Two separate analyses were performed. The first focussed on the detection of any AA (size ≥10mm or ≥25% villous or high-grade dysplasia) at the first surveillance attended by an individual. A separate analysis was performed with a diagnosis of CRC as the primary outcome. Results Of individuals with high risk findings at baseline colonoscopy, 12.3% of those attending first surveillance were found to have AA, 48.0% non-advanced adenoma, 39.1% no adenoma, and 0.5% CRC. In the case of individuals with intermediate risk findings at baseline, of those attending first surveillance, 8.0% were found to have AA, 35.3% non-advanced adenoma, 56.1% no adenoma, and 0.4% CRC. In those categorised as intermediate risk based on the finding of a single adenoma (≥10mm) at baseline, 6.3% of those attending first surveillance were found to have AA and 0.3% CRC. The most significant factor increasing the risk of AA at first surveillance was a higher total number of adenomas at baseline colonoscopy. Conclusions The rates of AA and CRC at first surveillance are relatively low and were found to be higher in the high risk group compared to intermediate risk. Those individuals categorised as intermediate risk based on a single adenoma (≥10mm) at baseline, had a particularly low rate of AA and CRC at first surveillance. These findings support the hypothesis that the incidence of AA and CRC are low at post-polypectomy surveillance colonoscopy. The particularly low yield in the subgroup with a single adenoma at baseline suggests that surveillance is not be needed in this group and may not be necessary for the intermediate risk cohort as a whole