New Diagnosis Of Colorectal Cancer Research Articles

Use and feasibility of a Lynch Syndrome predictive model for inherited colorectal and endometrial cancer in a low-middle income country.

While universal tumor testing for Lynch Syndrome (LS) is recommended in all new diagnoses of colorectal cancer (CC) and endometrial cancer (EC), the cost and availability of this test in low-resource settings poses challenges. The PREdiction Model for gene Mutations (PREMM5) is a clinical algorithm designed to assess the risk of an individual carrying estimates one's risk of carrying a LS mutation. This study aims to assess the feasibility of using PREMM5 to screen for LS risk in Guatemala. This cross-sectional pilot study enrolled 50 patients with colorectal or endometrial cancer receiving treatment at LIGA-INCAN, a cancer hospital in Guatemala City, between June 2022-July 2022. Patients were contacted by phone and administered the PREMM5 survey, followed by an additional feasibility questionnaire. Of the 50 participants, 62% of patients had a PREMM5 predicted probability of ≥ 2.5%, the threshold above which genetic testing is recommended. Almost all patients found the survey easy to complete (98%), were able to easily recall personal (90%) and family (88%) medical history, understood its purpose (94%), and reported an interest in (96%) and ability to (98%) act on the results if applicable. Our study shows the role of the PREMM5 as a feasible tool for identifying individuals at risk of carrying mutations associated with LS in this low-resource setting. By implementing the PREMM5 model, high risk individuals can be identified early, enabling timely interventions and improving outcomes in this at-risk population.

Comparison of the disease presentation of early- vs. later-onset colorectal cancer within the prospective ColoCare study.

91 Background: Within the United States (US), colorectal cancer (CRC) is the third most diagnosed cancer and the second leading cause of cancer-related fatalities, with a median age at diagnosis of 66 years. While the incidence of sporadic CRC is decreasing, the incidence in those aged 18-49 years has steadily increased. Younger patients are not often screened for CRC, and they are often diagnosed at a later stage of disease. Herein, we compare the presenting symptoms and stage at diagnosis of early-onset CRC to disease in those aged 50 or greater. Methods: The ColoCare Study is a prospective cohort enrolling individuals diagnosed with primary CRC across six cancer centers in the US and one site in Germany. Serial questionnaires administered at baseline assessed demographic characteristics and symptoms experienced prior to diagnosis, while clinical data such as staging and pathology were abstracted from medical records. For this analysis, only patients who had available age and tumor stage were included. Patients diagnosed <50 years old were categorized as “early-onset” and ≥50 as “later-onset.” Fisher’s exact test was used to compare demographics, disease state characteristics, and symptoms experienced by age group. Statistical significance was based on a two-sided alpha level of 0.05. Results: 1,996 patients were included in this analysis. Of these, 1,508 (76%) were later-onset (mean diagnosis age 64, range: 50-94), while 488 (24%) were early-onset (mean age: 42, range: 21-49). Demographic data was similar between early- and later-onset patients in terms of gender and primary site. Disease stage at diagnosis was significantly associated with age (p < 0.001). A higher proportion of early-onset patients had advanced disease at the time of diagnosis compared to later-onset for both stage III (43% vs 37%) and stage IV disease (28% vs 17%). For patients with available histologic data, younger patients were more likely to have vascular (35% vs 28%, p=0.03) and perineural invasion (33% vs 21%, p <0.001) at diagnosis. Early-onset patients were also more likely to report symptoms prior to diagnosis (95% vs 83%, p <0.001). Specifically, younger patients reported higher rates of abdominal pain (46% vs 23%, p < 0.001), blood in stool (71% vs 54%, p <0.001), and changes in bowel habits (54% vs 40%, p <0.001). General weakness and vomiting were also statistically more likely to be noted at presentation in early-onset patients. Conclusions: In this prospective real-world cohort analysis, patients with early-onset CRC are more likely to be diagnosed with more advanced disease at presentation than later-onset patients. This analysis highlights key symptoms that should raise awareness as possible indicators of a new diagnosis of CRC, even in individuals <50 years old. Additional disease comparisons between age groups will be presented at the meeting.

First-line Palliative Chemotherapy for Colorectal Cancer: a Population-based Analysis of Delivery and Outcomes in a Single-payer Health System

AimsClinical practice guidelines recommend palliative chemotherapy for most patients with metastatic colorectal cancer. However, outcomes observed in the real world compared with patients enrolled in clinical trials have not been sufficiently described. The objective of this study was to evaluate the delivery and outcomes of first-line palliative chemotherapy administered to patients with colorectal cancer in routine clinical practice compared with clinical trials. Materials and methodsUsing linked health administrative data, we carried out a retrospective population-level cohort study on patients diagnosed with colorectal cancer in Ontario, Canada from 2010 to 2019. Patient, disease and treatment characteristics were summarised. The primary outcome was median overall survival, stratified by treatment prescribed and age. Demographics and outcomes in this real-world population were compared with those from pivotal clinical trials. A multivariable Cox regression model reporting hazard ratios and 95% confidence intervals was used to determine factors associated with survival in patients receiving systemic treatment. ResultsWe identified 70 987 patients with a new diagnosis of colorectal cancer, of which 4613 received first-line chemotherapy for unresectable locally advanced or metastatic disease and formed the study cohort. Fifty-eight per cent were male and the mean age was 63 years. Most had colon cancer (69%), at least one comorbidity (73%) and lived in an urban location (79%). Less than half (47%) had surgery after diagnosis. The most common regimen prescribed was folinic acid, 5-fluorouracil and irinotecan (FOLFIRI) with bevacizumab or epidermal growth factor receptor inhibitors (EGFRi; n = 2784, 60%). Among all treated patients, the median overall survival was 17.1 months, with survival difference by regimen [median overall survival 18.3 for FOLFIRI with bevacizumab or EGFRi, 19.6 for folinic acid, 5-fluorouracil and oxaliplatin (FOLFOX)/capecitabine, oxaliplatin (XELOX) with bevacizumab or EGFRi, 13.6 for FOLFIRI alone and 7.8 for 5-fluorouracil or capecitabine]. Patients aged >80 years were most likely to have received single-agent 5-fluorouracil or capecitabine, and had inferior overall survival compared with their younger counterparts. Compared with pivotal clinical trials, patients in the real world had inferior overall survival outcomes despite similar demographic characteristics (including age and sex). ConclusionsIn this real-world population-based analysis of patients receiving first-line chemotherapy for unresectable locally advanced or metastatic colorectal cancer, survival outcomes were inferior to those reported in randomised trials despite similarities in age and sex. This information can be used when counselling patients in routine practice about expected outcomes.

1519. Increased incidence of colorectal cancer in Veteran Health Administration hospital patients with pyogenic liver abscess: A matched cohort study

Abstract Background Colorectal cancer (CRC) remains the third leading cause of death in the United States (US), and incidence has increased among patients < 50 years of age over the last few decades. Although many patients with early CRC remain asymptomatic, infections such as Streptococcus gallolyticus bacteremia, can be an early finding. There is increasing evidence that pyogenic liver abscesses (PLA) may also be associated with CRC. However, studies of US populations remain limited. Methods We retrospectively evaluated patients with a diagnosis of PLA at Veteran Health Administration hospitals across the US from 2003 to 2020. For each case, up to three uninfected controls matched for age (+/- 5), gender, and healthcare facilities at the time of index infection from the outpatient population were selected. PLA patients and matched controls were followed for ten years. Our primary outcome was a new diagnosis of CRC after index infection. Stratified cumulative incidence function plots with Gray’s test for equality were used to examine CRC incidence. Then we used Fine-Gray sub-distribution hazard regression models with interaction terms using the logarithm of time to estimate cause-specific time-dependent hazard ratios (HRs) for CRC incidence while accounting for mortality. Results We compared 8,294 PLA patients to 23,111 matched controls. Median age was 65.7 in PLA patients and 66.0 in matched controls. The median number of colonoscopies was ten in PLA patients and five in matched controls over the study period (p < 0.001). Our analysis revealed a 1.9% incidence of new CRC in the liver abscess group, compared to 0.8% in the matched cohort (p < 0.001, Figure 1). The multivariate sub-distribution hazard regression model showed higher time-dependent HRs of CRC up to two years from diagnosis of PLA but not higher afterward (Table 1). Incidence of colorectal cancer (CRC) in patients with liver abscess (dashed yellow line) compared to patients with no liver abscess (solid blue line). Our analysis revealed a 1.9% incidence of CRC in patients with liver abscess compared to 0.8% in the matched control cohort. Conclusion We found a significantly higher incidence of CRC for patients with PLA, especially during the first two years from diagnosis, although some of our findings may be explained by increased screening around the time of diagnosis. We believe our findings support the importance of CRC screening after the diagnosis of PLA. Disclosures Michihiko Goto, MD MSCI, Merck & Co.: Grant/Research Support.

S299 How Often Do We Provide Recommendations to Patients With Colorectal Cancer or Advanced Colonic Adenomas on When Their First-Degree Relatives Should Begin Colorectal Cancer Screening?

Introduction: First-degree relatives of patients found to have colorectal cancer (CRC) or advanced adenomas (AA) are advised to undergo colonoscopy starting at age 40, 10 years prior to time of CRC diagnosis in their first-degree relative, or at age of onset of AA in their first-degree relative; whichever comes first. Current guidelines recommend written communication to patients with CRC or AAs advising screening in first-degree relatives, which is particularly important in light of increased rates of early-onset CRC. We aimed to analyze the rate at which we provided guidance to patients found to have CRC or AAs on advising their first-degree relatives on timing of colonoscopy. Methods: We analyzed patients at our institution who underwent outpatient colonoscopies from November 29, 2021 to April 30, 2022. AAs were defined as adenomas ≥ 1 centimeter (cm) in size with tubulovillous, villous, high-grade dysplasia or traditional serrated features on histology, or sessile serrated lesions (SSLs) either ≥ 1 cm or with dysplasia. Patients with prior history of CRC or AA were excluded. We assessed how often appropriate screening recommendations were provided to patients with CRC or AAs for first-degree relatives based on documentation within 3 months of colonoscopy. Results: A total of 1332 colonoscopies were reviewed, with 47 patients meeting criteria for a new diagnosis of CRC or AA. Of these patients, 53.2% were African American and 57.4% were females (Table). The mean patient age was 56.9 years (± 10.6 years). Of these 47 patients, 3 patients (6.4%) were provided with specific written screening recommendations for first-degree relatives within 3 months of colonoscopy. Conclusion: In this retrospective analysis of patients found to have CRC or AAs on colonoscopy, only 6.4% were provided written guidance to advise first-degree relatives on appropriate timing for colonoscopy within three months after procedure. While verbal recommendations to patients may occur, patients may not recall specifics post-procedure or via telephone. Furthermore, guidelines call for recommendations for family members to be included in endoscopy reports, or through a letter meant to be shared with first-degree relatives. Considering these findings, we aim to provide an education intervention and templates for post-colonoscopy pathology letters and/or clinic visits to facilitate communication to patients with CRC or AAs on appropriately advising CRC screening in family members. Table 1. - Demographic information of patients found to have newly diagnosed colorectal cancer (CRC) or advanced adenoma (AA) on colonoscopy Number of patients (%) Known Family History of CRC or AA 6 (12.8%) Gender Male 20 (42.5%) Female 27 (57.4%) Ethnicity White 14 (29.8%) African American 25 (53.2%) Asian 3 (6.4%) Hispanic 2 (4.3%) Other 3 (6.4%) Age (mean) 56.9 years (± 10.6)

Changes in Cancer Screening Rates Following a New Cancer Diagnosis in a Primary Care Patient Panel

Although screenings for breast and colorectal cancer are widely recommended, patient screening rates vary greatly and remain below public health targets, and primary care physicians' (PCPs') counseling and referrals play critical roles in patients' use of cancer screenings. Recent adverse events may influence PCPs' decision-making, but it remains unknown whether cancer screening rates of PCPs' patients change after PCPs are exposed to new cancer diagnoses. To investigate whether PCPs' exposures to patients with new diagnoses of breast or colorectal cancer were associated with changes in screening rates for other patients subsequently visiting the affected PCPs. This cohort study used stacked difference-in-differences analyses of all-payer claims data for New Hampshire and Maine in 2009 to 2015. Participants were PCPs caring for patients. Data analysis was performed from June 2020 to May 2022. New diagnosis of a PCP's patient with breast cancer or colorectal cancer. Patients' breast and colorectal cancer screening rates within 1 year of a PCP visit. The sample included 3158 PCPs (1819 male PCPs [57.6%]) caring for 1 920 189 patients (1 073 408 female patients [55.9%]; mean [SD] age, 41.0 [21.9] years) aged 18 to 64 years. During the study period, 898 PCPs had a patient with a new diagnosis of breast cancer and 370 PCPs had a patient with a new diagnosis of colorectal cancer. In the preexposure period, 68 837 female patients (37.3% of those visiting a PCP) underwent breast cancer screening within 1 year of the visit, and 13 137 patients (10.1% of those visiting a PCP) underwent colorectal cancer screening within 1 year of the visit. For both cancer types, after exposure to a new cancer diagnosis, PCPs' cancer screening rates displayed a rapid, sustained increase. Breast cancer screening rates increased by 4.5 percentage points (95% CI, 3.0-6.1 percentage points; P < .001). Colorectal cancer screening rates increased by 1.3 percentage points (95% CI, 0.3-2.2 percentage points; P = .01). Observed breast cancer screening increases were higher for male PCPs than for female PCPs (3.1 percentage points; 95% CI, 0.4-5.8 percentage points; P = .03). This study found significant, sustained increases in cancer screening rates for patients visiting PCPs recently exposed to new breast and colorectal cancer diagnoses. These findings suggest that PCPs may update practice patterns on the basis of recent patient diagnoses. Future work should assess whether salient cues to PCPs about patient diagnoses when clinically appropriate can improve screening practices.

Periodontal disease as a risk factor for sporadic colorectal cancer: results from COLDENT study

Colorectal cancer remains the top leading cancer worldwide. Accumulating evidence suggests periodontal pathogens are involved in colorectal carcinogenesis, indicating the need for high-quality epidemiological evidence linking periodontal disease (PD) and colorectal cancer (CRC). Thus, we conducted the first population-based case–control study that was specifically designed to investigate the association between compromised oral health and sporadic CRC. A total of 348 incident cases of colon or rectal cancer, and 310 age and sex frequency-matched controls, from the Montreal island and Laval population participated in the study. Data were collected on PD and on several CRC risk factors using validated questionnaires. A life-course approach was used to document long-term history regarding lifestyle factors. Multivariable unconditional logistic regression analysis was used to estimate the rate ratio (RR) quantifying the association between CRC and PD. Results showed that the rate of new diagnosis of CRC in persons with a positive history of PD was 1.45 times higher than in those with a negative history of PD adjusting for age, sex, BMI, education, income, diabetes, family history of CRC, regular use of non-steroidal anti-inflammatory drugs, lifetime cumulative smoking, lifetime consumption of red meats, processed meats, and alcoholic drinks, and lifetime total physical activity score (adjusted RR = 1.45; 95% CI 1.04–2.01; p = 0.026). Our results support the hypothesis of an association between PD and sporadic CRC risk.

SP4.1.7 Colorectal Cancer: Pathway Disruptions as a Result of COVID-19

AimsCOVID-19 has impacted diagnosis and treatment of colorectal cancer. Efforts to minimise patient contact have caused delays in cancer pathways, generating a potential risk to patient care. We aim to identify the pandemic effect on colorectal referral pathways.MethodsAll cancer referrals during March-June 2020 were reviewed to obtain information on the timeline and planning of investigation and treatment. The data was compared to evidence from the same referral period in 2019.Results681 referrals were received during March-June 2020, compared to 1032 in 2019, indicating a 34% decrease. The majority of patients were reviewed in telephone clinic (76.2%) rather than physical appointments (15.4%). Although the commonest mode of investigation was endoscopy(46.2%), there was increased use of CT scan(35.8%). 114(17.1%) patients were not investigated, of which 40(35.1%) declined investigation, primarily due to COVID-19 apprehension. 6 patients were re-referred and 67(58.8%) were removed from the pathway for unknown reasons. 1 patient was subsequently admitted as an emergency. There were 44 new diagnoses of colorectal cancer based on MDT discussion, of which 14(31.8%) breached the investigation and 20(45.5%) the treatment date. 18 underwent curative surgery compared to 47 in the same period in 2019, indicating 61.7% less operative activity.ConclusionsCOVID-19 has changed surgical practice, forcing alternative clinic, investigation and treatment methods. Disruption of colorectal pathways is causing reduced referrals, investigation delays and less surgical activity. Delayed presentation with advanced disease may deprive the opportunity of treatment with curative intent.

Colon cancer in the older population

Fifty percent of new diagnoses of colorectal cancer are made in patients aged over 70 years, and 25% are aged 80 years or over. Older patients tend to have locally advanced colon cancer, with negative lymph nodes and without distant me­tastasis. Frequently the colon cancer is located on the right side. There is still a belief that older patients can not manage curative treatment regimens. This is based on the results of older studies showing higher rates of short-term morbidity and mortality. At present, we are observing significant improvements in the outcomes of older patients with colon cancer in high volume centers. This could be due to better preoperative staging, increased use of minimally invasive techniques, better anesthesiology and perioperative care, awareness of complications, expertise and high-volume care. A standardized pre-operative diagnostic approach, individualized surgical technique selection and tailored postoperative care are essential for the successful treatment of older patients. Furthermore, counseling and shared decision-making should be based on modern insights in surgical outcomes rather than outdated data.

Impact of the COVID-19 pandemic during Spain's state of emergency on the diagnosis of colorectal cancer.

We evaluate the impact of COVID-epidemic in colorectal cancer (CRC) diagnosis during Spain's state of emergency. We compared newly diagnosed patients with patients diagnosed in the same period of 2019. A new diagnosis of CRC decreased 48% with a higher rate of patients diagnosed in the emergency setting (12.1% vs. 3.6%; p = .048) and a lower rate diagnosed in the screening program (5.2% vs. 33.3%; p = .000). Fewer patients have been diagnosed with CRC, with a higher rate of patients diagnosed in an emergency setting.

Long-Term Risks of Parkinson’s Disease, Surgery, and Colorectal Cancer in Patients With Slow-Transit Constipation

Long-term outcomes of constipation have not been evaluated fully. We investigated the incidence of Parkinson's disease, constipation-related surgery, and colorectal cancer (CRC) in patients with constipation and slow-transit constipation (STC), followed up for up to 20 years. We collected data from 2165 patients (33.1% men; median patient age, 54 y; median symptom duration, 5.0 y) with a diagnosis of constipation (based on Rome II criteria) who underwent an anorectal function test and a colonic transit time study, from 2000 through 2010, at a tertiary university hospital in Seoul, South Korea. The presence of STC was determined from colonic transit time. We used the Kaplan-Meier method to analyze and compare cumulative probabilities of a new diagnosis of Parkinson's disease or CRC according to the presence of STC. The patients were followed up until the end of2019. During a median follow-up period of 4.7 years (interquartile range, 0.7-8.3 y), 10 patients underwent constipation-related surgery. The cumulative probabilities of constipation-related surgery were 0.7% at 5 years and 0.8% at 10 years after a diagnosis of constipation. Twenty-nine patients (1.3%) developed Parkinson's disease; the cumulative probabilities were 0.4% at 1 year, 1.0% at 5 years, and 2.6% at 10 years after a diagnosis of constipation. At 10 years, 1.3% of patients with STC required constipation-related surgery and 3.5% of patients with STC developed Parkinson's disease; in contrast, none of the patients without STC required constipation-related surgery (P= .003), and 1.5% developed Parkinson's disease (P= .019). In multivariate analysis, patient age of 65 years or older at the diagnosis of constipation (hazard ratio, 4.834; 95% CI, 2.088-11.190) and the presence of STC (hazard ratio, 2.477; 95% CI, 1.046-5.866) were associated independently with the development of Parkinson's disease. Only 5 patients had a new diagnosis of CRC during the follow-up period. The risk of CRC did not differ significantly between patients with vs without STC (P= .575). In a long-term follow-up study of patients with constipation in Korea, most patients had no severe complications. However, patients older than age 65 years with a new diagnosis of STC might be considered for Parkinson's disease screening.

Colorectal Cancer Risk Following Bariatric Surgery in a Nationwide Study of French Individuals With Obesity

Although bariatric surgery is effective against morbid obesity, the association of this surgery with the risk of colorectal cancer remains controversial. To assess whether bariatric surgery is associated with altered risk of colorectal cancer among individuals with obesity. This retrospective, population-based, multicenter, cohort study based on French electronic health data included 1 045 348 individuals with obesity, aged 50 to 75 years, and free of colorectal cancer at baseline. All inpatients with obesity having data recorded during a hospital stay between 2009 and 2018 by the French national health insurance information system database were followed up for a mean (SD) of 5.3 (2.1) years for those who did not undergo bariatric surgery and 5.7 (2.2) years for those who underwent bariatric surgery. Two groups of patients comparable in terms of age, sex, body mass index, follow-up, comorbidities, and conditions who did or did not undergo surgery were also obtained by propensity score matching. Bariatric surgery (n = 74 131), including adjustable gastric banding, sleeve gastrectomy, gastric bypass; or no bariatric surgery (n = 971 217). Primary outcome was incident colorectal cancer. Standardized incidence ratios were calculated using age-, sex-, and calendar year-matched colorectal cancer incidence among the general French population during the corresponding years. Secondary outcome was incident colorectal benign polyps. Among a total of 1 045 348 patients, the mean (SD) age was 57.3 (5.5) years for the 74 131 patients in the surgical cohort vs 63.4 (7.0) years for the 971 217 patients in the nonsurgical cohort. The mean (SD) follow-up was 6.2 (2.1) years for patients who underwent adjustable gastric banding, 5.5 (2.1) years for patients who underwent sleeve gastrectomy, and 5.7 (2.2) years for patients who underwent gastric bypass. In total, 13 052 incident colorectal cancers (1.2%) and 63 649 colorectal benign polyps were diagnosed. The rate of colorectal cancer was 0.6% in the bariatric surgery cohort and 1.3% in the cohort without bariatric surgery. In the latter cohort, 9417 cases were expected vs 12 629 observed, a standardized incidence ratio of 1.34 (95% CI, 1.32-1.36). In the bariatric surgery cohort, 428 cases were expected and 423 observed, a standardized incidence ratio of 1.0 (95% CI, 0.90-1.09). Propensity score-matched hazard ratios in comparable operated vs nonoperated groups were 0.68 (95% CI, 0.60-0.77) for colorectal cancer and 0.56 (95% CI, 0.53-0.59) for colorectal benign polyp. There were fewer new diagnoses of colorectal cancer after gastric bypass (123 of 22 343 [0.5%]) and sleeve gastrectomy (185 of 35 328 [0.5%]) than after adjustable gastric banding (115 of 16 460 [0.7%]), and more colorectal benign polyps after adjustable gastric banding (775 of 15 647 [5.0%]) than after gastric bypass (639 of 20 863 [3.1%]) or sleeve gastrectomy (1005 of 32 680 [3.1%]). The results of this nationwide cohort study suggested that following bariatric surgery, patients with obesity share the same risk of colorectal cancer as the general population, whereas for patients with obesity who do not undergo bariatric surgery, the risk is 34% above that of the general population.

Demographic trends in the incidence of young-onset colorectal cancer: a population-based study.

BackgroundEvidence is emerging that the incidence of colorectal cancer is increasing in young adults, but the descriptive epidemiology required to better understand these trends is currently lacking.MethodsA population‐based cohort study was carried out including all adults aged 20–49 years diagnosed with colorectal cancer in England between 1974 and 2015. Data were extracted from the National Cancer Registration and Analysis Service database using ICD‐9/10 codes for colorectal cancer. Temporal trends in age‐specific incidence rates according to sex, anatomical subsite, index of multiple deprivation quintile and geographical region were analysed using Joinpoint regression.ResultsA total of 56 134 new diagnoses of colorectal cancer were analysed. The most sustained increase in incidence rate was in the group aged 20–29 years, which was mainly driven by a rise in distal tumours. The magnitude of incident rate increases was similar in both sexes and across Index of Multiple Deprivation quintiles, although the most pronounced increases in incidence occurred in the southern regions of England.ConclusionColorectal cancer should no longer be considered a disease of older people. Changes in incidence rates should be used to inform future screening policy, preventative strategies and research agendas, as well as increasing public understanding that younger people need to be aware of the symptoms of colorectal cancer.

The association between colorectal cancer and prior antibiotic prescriptions: case control study

BackgroundAntibiotic use over several decades is believed to be associated with colorectal adenomas. There is little evidence, however, for the effect of more recent antibiotic use on frequency of colorectal cancers.MethodsA case control study used the RCGP’s Research and Surveillance Centre cohort of patients drawn from NHS England. In all, 35,214 patients with a new diagnosis of colorectal cancer between 1 January 2008 and 31 December 2018 were identified in the database and were matched with 60,348 controls. Conditional logistic regression was used to examine the association between antibiotic prescriptions and colorectal cancer.ResultsA dose-response association between colorectal cancers and prior antibiotic prescriptions was observed. The risk was related to the number and recency of prescriptions with a high number of antibiotic prescriptions over a long period carrying the highest risk. For example, patients prescribed antibiotics in up to 15 years preceding diagnosis were associated with a higher risk of colorectal cancer (odds ratio (OR) = 1.90, 95% confidence intervals (CI), 1.61–2.19, p < 0.001).ConclusionsAntibiotic use over previous years is associated with subsequent colorectal cancer. While the study design cannot determine causality, the findings suggest another reason for caution in prescribing antibiotics, especially in high volumes and over many years.

Indeterminate pulmonary nodules among patients with new diagnosis of colorectal cancer: Prevalence and significance assessment

Background: In Saudi Arabia, colorectal cancer (CRC) accounts for 11.5% of cancer incidence, where nearly one-third is metastatic. Global guidelines recommend accurate pretreatment staging to determine resectability and stage-directed treatment. Computed tomography (CT) scan is among the widely used imaging for staging. However, at times, the characterization of abnormalities detected by CT scan is perplexing. Indeterminate pulmonary nodules (IPNs) are nodules that are neither benign nor malignant, which are incidentally detected on baseline staging chest CT. We aimed to estimate the prevalence of IPN that were identified among CRC patients. Materials and Methods: We conducted a retrospective record review of all newly diagnosed CRC patients between June 2013 and June 2018 from an academic hospital in Jeddah, Kingdom of Saudi Arabia (KSA). Demographics and certain prespecified variables were collected. The presence of IPN on staging chest CT as per consultant radiologist report was documented, and the ability of other modalities to identify the nature of IPN was compared. Data were analyzed using SPSS and a P value < 0.05 was considered significant. Results: Of 283 CRC patients, 208 (73.5%) underwent chest CT, and the mean age was 57.4 years (±SD 13.1). The prevalence of IPN among CRC patients is 17.7%. Thirty IPN patients had a follow-up chest CT for IPN, which identified IPN nature in 18(60%) of them. The likelihood of IPN to be CRC-related metastasis was significantly associated with the presence of synchronous liver metastasis (P = 0.0005), younger age (P = 0.022), and colon cancer (P = 0.011). Conclusion: The prevalence of IPN was 17.7%, which is different in comparison to other studies from different countries. There is a vital need for unified guidelines describing IPN to accurately stage CRC patients, decrease unnecessary follow-ups, and acquire the exact prevalence of IPN.

Investigation on the hereditary basis of colorectal cancers in an African population with frequent early onset cases

BackgroundApproximately 25% of colorectal cancer patients in sub-Saharan Africa are younger than 40 years, and hereditary factors may contribute. We investigated the frequency and patterns of inherited colorectal cancer among black Zimbabweans.MethodsA population-based cross-sectional study of ninety individuals with a new diagnosis of colorectal cancer was carried out in Harare, Zimbabwe between November 2012 and December 2015. Phenotypic data was obtained using interviewer administered questionnaires, and reviewing clinical and pathology data. Cases were screened for mismatch repair deficiency by immunohistochemistry and/or microsatellite instability testing, and for MLH1, MSH2 and EPCAM deletions using multiplex ligation-dependent probe amplification. Next generation sequencing using a 16-gene panel was performed for cases with phenotypic features consistent with familial colorectal cancer. Variants were assessed for pathogenicity using the mean allele frequency, phenotypic features and searching online databases.ResultsThree Lynch syndrome cases were identified: MSH2 c.2634G>A pathogenic mutation, c.(1896+1_1897–1)_(*193_?)del , and one fulfilling the Amsterdam criteria, with MLH1 and PMS2 deficiency, but no identifiable pathogenic mutation. Two other cases had a strong family history of cancers, but the exact syndrome was not identified. The prevalence of Lynch syndrome was 3·3% (95% CI 0·7–9·4), and that of familial colorectal cancer was 5·6% (95% CI, 1·8–12·5).ConclusionsIdentifying cases of inherited colorectal cancer in sub-Saharan Africa is feasible, and our findings can inform screening guidelines appropriate to this setting.

Do Indigenous patients in Australia's Northern Territory present with more advanced colorectal cancer? A cohort study based on registry data.

Previous studies show that Indigenous Australians (IndA) of the Northern Territory (NT) present later and have lower survival for colorectal cancer (CRC) compared with non-Indigenous (NI) Territorians. This study compared the odds of presenting with advanced-stage CRC between IndA and NI adjusted for demographic, histopathological and surgical features. A cohort study of NT Cancer Registry (NTCR) CRC cases from 2005 to 2014. All (667) persons notified to the NTCR with a new diagnosis of CRC were included, of which 504 had sufficient data for analysis. The NTCR was used for case identification and linked to available hospital clinical data. The principal exposure was IndA compared with NI and the principal outcome was odds of presenting with advanced-stage tumour (III and IV) compared with early-stage (I and II). Univariable and multivariable logistic regression were performed on all relevant variables. Univariable logistic regression found no difference in the odds of advanced CRC between IndA and NI (odds ratio (OR) 0.99, 95% confidence interval (CI) 0.56-1.76, P = 0.982). This effect remained insignificant adjusted for the effects of sex, tumour position, remoteness and time period (OR 0.85, 95% CI 0.47-1.55, P = 0.606) and when adjusted for tumour grade, lympho-vascular invasion, lymph node harvest and emergency status (OR 1.39, 95% CI 0.64-3.03, P = 0.401). In distinction from previous studies, there was no evidence that IndA of the NT presented with later stage CRC in 2005-2014. Other factors (incomplete treatment or comorbidity) may be responsible for the continued observed survival disparity.

Epidemiology and Mechanisms of the Increasing Incidence of Colon and Rectal Cancers in Young Adults

In contrast to the decreasing incidence of colorectal cancer (CRC) in older populations, the incidence has nearly doubled in younger adults since the early 1990s. Approximately 1 in 10 new diagnoses of CRC are now made in individuals 50 years or younger. Patients' risk of CRC has been calculated largely by age and family history, yet 3 of 4 patients with early-onset CRC have no family history of the disease. Rapidly increasing incidence rates in younger people could result from generational differences in diet, environmental exposures, and lifestyle factors. We review epidemiologic trends in CRC, data on genetic and nongenetic risk factors, and new approaches for determining CRC risk. These may identify individuals likely to benefit from early screening and specialized surveillance.

Vitamin D Levels in Patients with Colorectal Cancer Before and After Treatment Initiation.

We aimed to described 25-hydroxyvitamin D [25(OH)D] levels in newly diagnosed colorectal cancer (CRC) patients and to re-evaluate levels after chemotherapy. Permanent residents of the San Francisco Bay Area with a new CRC diagnosis of any stage were recruited prior to any non-surgical therapy. Serum 25(OH)D levels were measured at time of diagnosis and 6-month follow-up. Supplement use was not restricted. The primary endpoint was the frequency of vitamin D deficiency in patients with newly diagnosed CRC of all stages. The Kruskal-Wallis and Spearman correlation tests were used to evaluate associations of patient characteristics with 25(OH)D levels. Median 25(OH)D level at baseline was 27.0ng/mL (range 7.2, 59.0); 65% of patients had insufficient levels (25(OH)D < 30ng/mL) (n = 94). Race, disease stage, multivitamin use, vitamin D supplementation, and county of residence were associated with baseline 25(OH)D levels (P < 0.05). The median change in 25(OH)D from baseline to 6months was - 0.7ng/mL [- 19.4, 51.7] for patients treated with chemotherapy (n = 58) and 1.6ng/mL [- 6.4, 33.2] for patients who did not receive chemotherapy (n = 19) (P = 0.26). For patients who received vitamin D supplementation during chemotherapy, the median 25(OH)D change was 8.3ng/mL [- 7.6, 51.7] versus - 1.6 [- 19.4, 24.3] for chemotherapy patients who did not take vitamin D supplements (P = 0.02). Among patients with a new diagnosis of CRC, most patients were found to have 25(OH)D levels consistent with either deficiency or insufficiency. In the subset of patients who received chemotherapy and took a vitamin D supplement, serum 25(OH)D levels increased, suggesting that vitamin D repletion is a feasible intervention during chemotherapy.

Racialized economic segregation and stage at diagnosis of colorectal cancer in the United States.

In order to improve colorectal cancer outcomes in the United States, there is an urgent need for research on the drivers of geographic disparities in stage at diagnosis. Our objective was to determine the effects of racialized economic segregation on the odds of late diagnosis. Among 187,843 adults (≥ 18years old) with new diagnoses of colorectal cancer reported to the Surveillance, Epidemiology and End-Results program between 1st January 2009 and 31st December 2013, exposure to racialized economic segregation was measured at the county-level using Index of Concentration at the Extremes metrics. Multilevel logistic regression models including registry and county random effects were fit to examine the association between racialized economic segregation and odds of metastatic disease at time of diagnosis. Odds of late diagnosis were greatest in counties with the lowest compared to highest quintile for racial and economic privilege (OR 1.14; 95% CI 1.09-1.20). In multilevel models adjusting for individual-level covariates, odds of late diagnosis were greater for all patients except those living in counties with the highest concentration of white high-income individuals. There was significant effect modification of this relationship by age, with greater adverse effects for younger adults (OR 1.16; 95% CI 1.02-1.32) than older adults (OR 1.06; 95% CI 1.00-1.11). Racialized economic segregation was strongly associated with access to affordable healthcare. Spatial social polarization, quantified in relation to racialized economic segregation, increases the odds of late diagnosis of colorectal cancer for persons residing in the least compared to most privileged counties.