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Aim: As multidisciplinary treatment strategies for colorectal cancer have improved, aggressive surgical resection has become commonplace. Multivisceral and extended resections offer curative‐intent resection with significant survival benefit. However, limited data exist regarding the feasibility and oncological efficacy of performing extended resection via a minimally invasive approach. The aim of this study was to determine the perioperative and long‐term outcomes following robotic extended resection for colorectal cancer. Method: We describe the population of patients undergoing robotic multivisceral resection for colorectal cancer at our single institution. We evaluated perioperative details and investigated short‐ and long‐term outcomes, using the Kaplan–Meier method to analyse overall and recurrence‐free survival. Results: Among the 86 patients most tumours were T3 (47%) or T4 (47%) lesions in the rectum (78%). Most resections involved the anterior compartment (72%): bladder (n = 13), seminal vesicle/vas deferens (n = 27), ureter (n = 6), prostate (n = 15) and uterus/vagina/adnexa (n = 27). Three cases required conversion to open surgery; 10 patients had grade 3 complications. The median hospital stay was 4 days. Resections were R0 (>1 mm) in 78 and R1 (0 to ≤1 mm) in 8, with none being R2. The average nodal yield was 26 and 48 (55.8%) were pN0. Three‐year overall survival was 88% and median progression‐free survival was 19.4 months. Local recurrence was 6.1% and distant recurrence was 26.1% at 3 years. Conclusion: Performance of multivisceral and extended resection on the robotic platform allows patients the benefit of minimally invasive surgery while achieving oncologically sound resection of colorectal cancer. [ABSTRACT FROM AUTHOR]

Objective: External exposures, the host, and the microbiome interact in oncology. We aimed to investigate tumoral microbiomes in young-onset rectal cancers (YORCs) for profiles potentially correlative with disease etiology and biology. Background: YORC is rapidly increasing, with 1 in 4 new rectal cancer cases occurring under the age of 50 years. Its etiology is unknown. Methods: YORC (<50 y old) or later-onset rectal cancer (LORC, ≥50 y old) patients underwent pretreatment biopsied of tumor and tumor-adjacent normal (TAN) tissue. After whole genome sequencing, metagenomic analysis quantified microbial communities comparing tumors versus TANs and YORCs versus LORCs, controlling for multiple testing. Response to neoadjuvant therapy (NT) was categorized as major pathological response (MPR, ≤10% residual viable tumor) versus non-MPR. Results: Our 107 tumors, 75 TANs from 37 (35%) YORCs, and 70 (65%) LORCs recapitulated bacterial species were previously associated with colorectal cancers (all P< 0.0001). YORC and LORC tumoral microbiome signatures were distinct. After NT, 13 patients (12.4%) achieved complete pathologic response, whereas MPR occurred in 47 patients (44%). Among YORCs, MPR was associated with Fusobacterium nucleaum, Bacteroides dorei, and Ruminococcus bromii (all P< 0.001), but MPR in LORC was associated with R. bromii (P<0.001). Network analysis of non-MPR tumors demonstrated a preponderance of oral bacteria not observed in MPR tumors. Conclusions: Microbial signatures were distinct between YORC and LORC. Failure to achieve an MPR was associated with oral bacteria in tumors. These findings urge further studies to decipher correlative versus mechanistic associations but suggest a potential for microbial modulation to augment current treatments. [ABSTRACT FROM AUTHOR]

Objective: Lynch Syndrome (LS) carriers have a significantly increased risk of developing colorectal cancer (CRC) during their lifetimes. Further stratification of this patient population may help in identifying additional risk factors that predispose to colorectal carcinogenesis. In most LS patients CRC may arise from adenomas, although an alternative non-polypoid carcinogenesis pathway has been proposed for PMS2 carriers. Using data from our institutional LS cohort, our aim was to describe our current colorectal screening outcomes with a focus on the incidence of adenomas in the context of different MMR genotypes and patient demographics such as gender, race, and ethnicity. Design: We collected demographics, genetic, colonoscopy, and pathology results from a total of 163 LS carriers who obtained regular screening care at MD Anderson Cancer Center. Data were extracted from the electronic health records into a REDCap database for analysis. Logistic regressions were performed to measure the association between MMR variants and the likelihood of adenomas, advanced adenomas, and CRC. Then, we analyzed the cumulative incidences of these outcomes for the first 36 months following enrollment using Kaplan-Meier incidence curves, and Cox proportional hazard regressions. Results: On multivariate analysis, age (=45 years old) was associated with an increased risk of developing adenomas (P=0.034). Patients with a prior or active cancer status were less likely to develop adenomas (P=0.015), despite of the lack of association between surgical history with this outcome (P=0.868). We found no statistically significant difference in likelihood of adenoma development between MLH1 and MSH2/EPCAM, MSH6, and PMS2 carriers. Moreover, we observed no statistically significant difference in the likelihood of advanced adenomas or CRC for any measured covariates. On Cox proportional hazard, compared to MLH1 carriers, the incidence of adenomas was highest among MSH2/EPCAM carriers during for the first 36-months of follow-up (P<0.001). We observed a non-statistically significant trend for Hispanics having a higher and earlier cumulative incidence of adenomas compared to non-Hispanics (P=0.073). No MMR carrier was more likely to develop advanced adenomas. No difference in the incidence of CRC by MMR gene (P=0.198). Conclusion: Screening recommendations for CRC in LS patients should be based on specific MMR variants and should also be tailored to consider patient demographics. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer in young adults is on the rise. This rise combined with delayed childbearing increases the likelihood of colorectal cancer diagnosed during pregnancy or in the postpartum period. Methods: Electronic health records were used to identify individuals with colorectal cancer in pregnancy or the postpartum period from 1 August 2007 to 1 August 2019. Results: Forty-two cases were identified. Median age at diagnosis was 33 years. Most (93%) were diagnosed in an advanced stage (III or IV) and had left-sided colorectal cancer tumors (81%). Molecular analysis was completed in 18 (43%) women with microsatellite status available in 40 (95%). The findings were similar to historical controls. Sixty percent were diagnosed in the postpartum period. Common presenting symptoms were rectal bleeding and abdominal pain. Conclusion: Currently there is no consensus recommendation regarding how to manage colorectal cancer during pregnancy. Given the overlapping symptoms with pregnancy, patients often present with advanced disease. We encourage all health care professionals caring for pregnant women to fully evaluate women with persistent gastrointestinal symptoms to rule out colorectal cancer. [ABSTRACT FROM AUTHOR]

Lynch syndrome (LS) carriers develop mismatch repair–deficient neoplasia with high neoantigen (neoAg) rates. No detailed information on targetable neoAgs from LS precancers exists, which is crucial for vaccine development and immune-interception strategies. We report a focused somatic mutation and frameshift-neoAg landscape of microsatellite loci from colorectal polyps without malignant potential (PWOMP), precancers, and early-stage cancers in LS carriers. We generated paired whole-exome and transcriptomic sequencing data from 8 colorectal PWOMP, 41 precancers, 8 advanced precancers, and 12 early-stage cancers of 43 LS carriers. A computational pipeline was developed to predict, rank, and prioritize the top 100 detected mutated neoAgs that were validated in vitro using ELISpot and tetramer assays. Mutation calling revealed >10 mut/Mb in 83% of cancers, 63% of advanced precancers, and 20% of precancers. Cancers displayed an average of 616 MHC-I neoAgs/sample, 294 in advanced precancers, and 107 in precancers. No neoAgs were detected in PWOMP. A total of 65% of our top 100 predicted neoAgs were immunogenic in vitro, and were present in 92% of cancers, 50% of advanced precancers, and 29% of precancers. We observed increased levels of naïve CD8+ and memory CD4+ T cells in mismatch repair–deficient cancers and precancers via transcriptomics analysis. Shared frameshift-neoAgs are generated within unstable microsatellite loci at initial stages of LS carcinogenesis and can induce T-cell responses, generating opportunities for vaccine development, targeting LS precancers and early-stage cancers. This study provides the combined mutational and transcriptomic landscape along with a catalog of immunologically validated neoantigens in Lynch syndrome colonic precancers and tumors that will facilitate cancer immunoprevention strategies. [ABSTRACT FROM AUTHOR]

Multigene panel tests for hereditary cancer syndromes are increasingly utilized in the care of colorectal cancer (CRC) and polyposis patients. However, widespread availability of panels raises a number of questions including which patients should undergo testing, which genes should be included on panels, and the settings in which panels should be ordered and interpreted. To address this knowledge gap, key questions regarding the major issues encountered in clinical evaluation of hereditary CRC and polyposis were designed by the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer Position Statement Committee and leadership. A literature search was conducted to address these questions. Recommendations were based on the best available evidence and expert opinion. This position statement addresses which genes should be included on a multigene panel for a patient with a suspected hereditary CRC or polyposis syndrome, proposes updated genetic testing criteria, discusses testing approaches for patients with mismatch repair proficient or deficient CRC, and outlines the essential elements for ordering and disclosing multigene panel test results. We acknowledge that critical gaps in access, insurance coverage, resources, and education remain barriers to high-quality, equitable care for individuals and their families at increased risk of hereditary CRC. [ABSTRACT FROM AUTHOR]

Lifestyle factors related to energy balance, such as excess body weight, poor diet, and physical inactivity, are associated with risk of sporadic endometrial cancer (EC) and colorectal cancer (CRC). There are limited data on energy balance-related lifestyle factors and EC or CRC risk among individuals with lynch syndrome, who are at extraordinarily higher risk of developing EC or CRC. We conducted a systematic review of evidence related to weight status, weight change, dietary habits, and physical activity on EC and CRC risk among individuals with lynch syndrome. Findings are reported narratively. We searched Medline, EMBASE, CENTRAL, PubMed, and clinicaltrials.gov up to June 14th, 2018. In total, 1060 studies were identified and 16 were included. Three studies were related to EC and 13 to CRC. Overall, evidence suggests that weight status/weight change may not be associated with EC risk and multivitamin and folic-acid supplementation may be associated with decreased EC risk. Early-adulthood overweight/obese weight-status and adulthood weight-gain may be associated with increased CRC risk, whereas multivitamin supplementation, tea and high fruit intake, and physical activity may be associated with decreased CRC risk. Current evidence proposes that recommendations related to weight, some dietary habits, and physical activity recommended for the general public are also relevant to individuals with lynch syndrome. More research is needed, specifically prospective cohorts and randomized controlled trials, to determine if tailored recommendations are needed among individuals with lynch syndrome. [ABSTRACT FROM AUTHOR]

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Despite the availability of effective colorectal cancer (CRC) screening strategies, up to 10% of CRC patients present with obstructive symptoms as the first sign of disease. For patients with acute or subacute malignant obstruction that requires urgent intervention, treatment options include endoscopic stenting as a bridge to surgery, one-stage surgical resection and anastomosis, or diverting ostomy which may or may not be followed by later tumor resection and stoma closure. However, to date, there is no consensus guideline for the optimal approach to manage malignant colorectal obstruction. This article aims to illustrate clinical scenarios in palliative, curative, and potentially curative settings, and delineate the key factors to be considered when making an individualized decision in order to determine the optimal treatment. [ABSTRACT FROM AUTHOR]

Greater physical activity is associated with a decrease in risk of colorectal cancer for the general population; however, little is known about its relationship with colorectal cancer risk in people with Lynch syndrome, carriers of inherited pathogenic mutations in genes affecting DNA mismatch repair (MMR). We studied a cohort of 2,042 MMR gene mutations carriers (n = 807, diagnosed with colorectal cancer), from the Colon Cancer Family Registry. Self‐reported physical activity in three age‐periods (20–29, 30–49 and ≥50 years) was summarized as average metabolic equivalent of task hours per week (MET‐hr/week) during the age‐period of cancer diagnosis or censoring (near‐term exposure) and across all age‐periods preceding cancer diagnosis or censoring (long‐term exposure). Weighted Cox regression was used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) for the association between physical activity and colorectal cancer risk. Near‐term physical activity was associated with a small reduction in the risk of colorectal cancer (HR ≥35 vs. <3.5 MET‐hr/week, 0.71; 95% CI, 0.53–0.96). The strength and direction of associations were similar for long‐term physical activity, although the associations were not nominally significant. Our results suggest that physical activity is inversely associated with the risk of colorectal cancer for people with Lynch syndrome; however, further confirmation is warranted. The potential modifying effect of physical activity on colorectal cancer risk in people with Lynch syndrome could be useful for risk prediction and support counseling advice for lifestyle modification to reduce cancer risk. What's new? Physical activity is known to reduce colorectal cancer risk in the general population. Little is known, however, on the effect of physical activity for people with Lynch syndrome, who have a strong predisposition to colorectal cancer due to germline mutations in DNA mismatch repair genes. This study of 2,042 mutation carriers suggests that physical activity is inversely associated with colorectal cancer risk for people with Lynch syndrome. If confirmed, the potential modifying effect of physical activity could be useful for risk prediction in this sub‐population and inform recommendations on lifestyle modifications as a way to reduce colorectal cancer risk. [ABSTRACT FROM AUTHOR]

This study evaluated provider satisfaction in a sample of colorectal cancer ( CRC) survivors with and without Lynch syndrome ( LS). Participants were case-case-matched CRC survivors with ( n = 75) or without ( n = 75) LS (mean age of 55; range: 27-93). Participants completed a mailed questionnaire assessing demographics, clinical characteristics, healthcare utilization, psychosocial variables, and provider satisfaction. LS CRC survivors reported lower provider satisfaction scores on three subscales of the Primary Care Assessment Survey: communication (78.14 vs. 83.96; P < 0.05), interpersonal treatment (78.58 vs. 85.30; P < 0.05), and knowledge of the patient (60.34 vs. 69.86; P < 0.01). Among LS CRC survivors, predictors for mean communication and trust subscale scores were location of treatment and socioeconomic status. Higher mean depression scores also were associated with trust, while social support predicted higher satisfaction with communication. Sporadic CRC survivor satisfaction is driven largely by age (communication, interpersonal treatment) and patient anxiety (communication), while seeing a provider more often was associated with increased satisfaction with knowledge of the patient. LS CRC survivors reported lower levels of provider satisfaction than sporadic CRC survivors. LS survivors who received care at The University of Texas MD Anderson Cancer Center, a comprehensive cancer center ( CCC), reported higher satisfaction than those receiving care at other institutions. Depressive symptoms and socioeconomic status may impact provider satisfaction ratings. Exploration of other potential predictors of provider satisfaction should be examined in this population. Additionally, further research is needed to examine the potential impact of provider satisfaction on adherence to medical recommendations in LS CRC survivors, particularly those being treated outside of CCCs. [ABSTRACT FROM AUTHOR]

Purpose: To compare health-related quality of life (HRQoL) in colorectal cancer (CRC) survivors with sporadic CRC to those with hereditary cancer, specifically Lynch syndrome (LS). Methods: Participants completed a mailed self-administered questionnaire that assessed, among other things, demographics, clinical characteristics, and health-related quality of life. Using a case-case design, CRC survivors with LS or sporadic cancer were matched on age, sex, race/ethnicity, cancer stage, geography, and time since diagnosis. Participants were recruited from patient registries at The University of Texas MD Anderson Cancer Center (MD Anderson) (n = 33 LS; n = 75 sporadic) and through social media (n = 42 LS). The final sample included 71 LS and 74 sporadic CRC survivors. Results: For LS patients, the mean FACT-C HRQoL score was 84.8 (11.9) [Median = 86.0; Interquartile Range-17] compared to sporadic patients mean score of 85.8 (16.7) [Median = 92.0; Interquartile Range-21], which indicates high quality of life for both groups. LS patients and sporadic CRC patients had similar HRQoL mean scores across 7 different HRQoL metrics, with no significant differences between groups. Exploratory regression analyses indicate some differences in known predictors of HRQoL by group despite no bivariate differences. Conclusions: HRQoL is an important component of survivorship in CRC patients. Given the clinical distinctions between LS and sporadic patients, we expected to find significant differences between these patients. However, the patients' experiences/quality of life does not appear to illustrate such a clear dissimilarity within CRC survivors. Given the limited data in this area, larger studies, ideally with data obtained from multiple sites, is needed to better investigate the alignment between clinical determination and patient experience as well as to explore the relationship between HRQOL, treatment regimens, and health outcomes. [ABSTRACT FROM AUTHOR]

• This study examined outcomes of panel testing of colorectal cancer genes in patients with colorectal cancer at 35 or younger. • The results confirmed a previous study showing a high incidence of hereditary colorectal cancer syndromes in young patients. • Disease-specific panel testing did not increase the yield of diagnostic workup over phenotype-driven testing. • Broader panels may increase the yield but also identify more uncertain variants in young patients with colorectal cancer. Adolescents and young adults with colorectal cancer (CRC) have attracted recent attention, with a hereditary syndrome identified in one-third of patients diagnosed ≤ 35. We aimed to study this population to determine if a CRC-specific gene panel increased the yield of testing. Patients with CRC ≤ 35 evaluated from 05/2014–11/2017 were identified from the genetic counseling database. Records were reviewed for personal/family history and genetic counseling outcomes. One hundred forty-three patients with CRC ≤ 35 were included. One hundred four (72.7%) underwent CRC panel testing. Thirty-nine (27.2%) had syndrome-directed testing, declined, or were lost to follow-up. Forty-two patients had a genetic syndrome (29.4%). Twenty-four of the 42 hereditary patients (57.1%) were identified via syndrome-directed testing. Mutations identified via panel testing were consistent with patient personal/family history. Thirty-three patients had at least one variant of uncertain significance. Hereditary syndromes were identified in 29.4% of patients. Panel testing in patients without a phenotype did not increase diagnostic yield, but identified variants in one-third. Disease-specific panel testing is of low yield in young patients without a suggestive personal/family history. Testing broader panels may increase the yield of mutation pick-up in this population, although at the expense of identifying variants. [ABSTRACT FROM AUTHOR]