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Definitive radiation therapy with concurrent chemotherapy is curative for nonmetastatic squamous cell carcinoma of the anus (SCCA). However, the true effect of chemoradiation on long-term functional outcomes is poorly understood owing to limited follow-up and patient-reported outcomes (PROs).We conducted a cross-sectional survey of 248 patients with SCCA treated with definitive intensity modulated radiation and concurrent chemotherapy from 2010 to 2018 who were alive and without recurrence. PRO measures were collected, including Functional Assessment of Cancer Therapy-General (FACT-G7), Fecal Incontinence Quality of Life (FIQoL), Low Anterior Resection Syndrome (LARS), and International Consultation on Incontinence Questionnaires (ICIQ). Models were used to determine the association between demographic, tumor, treatment, and dosimetric data with PROs.One hundred twelve (45%) patients completed PROs. Median [interquartile range (IQR)] time from radiation completion to survey was 51 [37-85] months. The median scores [IQR] for FACT-G7, FIQoL, and LARS were 21 [15-24], 14 [11-16], and 32 [25-37], respectively. For men, median subscores [IQR] for ICIQ voiding and incontinence subscores were 5 [2-6] and 1 [1-3], respectively. For women, median subscores [IQR] for ICIQ voiding, incontinence, and filling were 1 [1-3], 5 [3-8], and 4 [2-5], respectively. Higher (better) FIQoL scores were associated with higher (better) FACT-G7 scores (β = 0.83; 95% confidence interval, 0.58-1.09; P.001), and higher (worse) LARS scores were associated with lower (worse) FACT-G7 scores (β = -0.22; 95% confidence interval, -0.31 to -0.13; P.001). A separate multivariable analysis revealed higher bowel bag D1% was associated with lower (worse) FIQoL (P = .001) and higher (worse) LARS (P = .003) scores. Higher bladder V40 Gy was associated with increased (worse) ICIQ voiding subscore (P = .001).Patients treated with modern chemoradiation for SCCA experience significant long-term bowel toxic effects with considerable effect on quality of life. Minimizing bowel hotspots and bladder V40 Gy may improve bowel and urinary function. Other interventions to reduce long-term toxic effects and improve quality of life are needed.

Lateral pelvic lymph node (LPLN) metastases are an important cause of preventable local failure in rectal cancer. The aim of this study was to evaluate clinical and oncological outcomes following magnetic resonance imaging (MRI)-directed surgical selection for lateral pelvic lymph node dissection (LPLND) after total neoadjuvant therapy (TNT).A retrospective consecutive cohort analysis was performed of rectal cancer patients with enlarged LPLN on pretreatment MRI. Patients were categorized as LPLND or non-LPLND. The main outcomes were lateral local recurrence rate, perioperative and oncological outcomes and factors associated with decision making for LPLND.A total of 158 patients with enlarged pretreatment LPLN and treated with TNT were identified. Median follow-up was 20 months (interquartile range 10-32). After multidisciplinary review, 88 patients (56.0%) underwent LPLND. Mean age was 53 (SD±12) years, and 54 (34.2%) were female. Total operative time (509 vs 429 minutes; P =0.003) was greater in the LPLND group, but median blood loss ( P =0.70) or rates of major morbidity (19.3% vs 17.0%) did not differ. LPLNs were pathologically positive in 34.1%. The 3-year lateral local recurrence rates (3.4% vs 4.6%; P =0.85) did not differ between groups. Patients with LPLNs demonstrating pretreatment heterogeneity and irregular margin (odds ratio, 3.82; 95% confidence interval: 1.65-8.82) or with short-axis ≥5 mm post-TNT (odds ratio 2.69; 95% confidence interval: 1.19-6.08) were more likely to undergo LPLND.For rectal cancer patients with evidence of LPLN metastasis, the appropriate selection of patients for LPLND can be facilitated by a multidisciplinary MRI-directed approach with no significant difference in perioperative or oncologic outcomes.

BackgroundYoung adults and other working-age adults with cancer are at risk for cancer-related financial toxicity (FT), including material hardships, depletion of coping resources, and psychological burden. This study compares FT domains in young adults (18-39years old) (YAs), other working-age adults (40-64years old), and older adults (≥65years old) receiving cancer care.MethodsA total of 311 adults were surveyed using the multi-domain Economic Strain and Resilience in Cancer instrument measuring FT (0-10 score indicating least to greatest FT; score ≥5 severe FT). Participants were receiving ambulatory care from March-September 2019. Associations of age with overall FT and material hardship, coping resource depletion, and psychological burden FT domains were tested using Kruskal-Wallis and χ2 tests and multivariable generalized linear models with gamma distribution.ResultsYAs (median age, 31.5years) comprised 9.6% of the sample; other working-age adults comprised 56.9%. Overall, material, coping, and psychological FT scores were worse in younger age adults versus older adults (P&nbsp

PURPOSE To develop recommendations for adjuvant therapy for patients with resected stage II colon cancer. METHODS ASCO convened an Expert Panel to conduct a systematic review of relevant studies and develop recommendations for clinical practice. RESULTS Twenty-one observational studies and six randomized controlled trials met the systematic review inclusion criteria. RECOMMENDATIONS Adjuvant chemotherapy (ACT) is not routinely recommended for patients with stage II colon cancer who are not in a high-risk subgroup. Patients with T4 tumors are at higher risk of recurrence and should be offered ACT, whereas patients with other high-risk factors, including sampling of fewer than 12 lymph nodes in the surgical specimen, perineural or lymphovascular invasion, poorly or undifferentiated tumor grade, intestinal obstruction, tumor perforation, or grade BD3 tumor budding, may be offered ACT. The addition of oxaliplatin to fluoropyrimidine-based ACT is not routinely recommended, but may be offered as a result of shared decision making. Patients with mismatch repair deficiency/microsatellite instability tumors should not be routinely offered ACT; if the combination of mismatch repair deficiency/microsatellite instability and high-risk factors results in a decision to offer ACT, oxaliplatin-containing chemotherapy is recommended. Duration of oxaliplatin-containing chemotherapy is also addressed, with recommendations for 3 or 6 months of treatment with capecitabine and oxaliplatin or fluorouracil, leucovorin, and oxaliplatin, with decision making informed by key evidence of 5-year disease-free survival in each treatment subgroup and the rate of adverse events, including peripheral neuropathy. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines .

Background Although intensity-modulated radiation therapy (IMRT) is considered the standard of care for the treatment of squamous cell carcinoma of the anus (SCCA), few large series have reported oncologic outcomes and toxicities. In this retrospective report, we aim to describe outcomes and toxicities after IMRT-based chemoradiation (CRT) for the treatment of SCCA, evaluate the impact of dose escalation (>54 Gy), and compare concurrent fluoropyrimidine in combination with either mitomycin or with cisplatin as chemosensitizers. Methods Patients treated at The University of Texas MD Anderson Cancer Center between January 1, 2003 and December 31, 2018 with IMRT-based CRT were included. Median time to locoregional recurrence, time to colostomy, and overall survival were estimated using the Kaplan–Meier method. Results A total of 428 patients were included; median follow-up was 4.4 years. Three hundred and thirty-four patients (78.0%) were treated with concurrent cisplatin and fluoropyrimidine, and 160 (37.4%) with >54 Gy. Two- and 5-year freedom from locoregional failure, freedom from colostomy failure, and overall survival were 86.5% and 81.2%, respectively, 90.0% and 88.3%, respectively, and 93.6% and 85.8%, respectively. Neither dose escalation nor mitomycin-based concurrent chemotherapy resulted in improved outcomes. Mitomycin-based concurrent chemotherapy was associated with in approximately 2.5 times increased grade 3 or greater acute toxicity. Radiation dose >54 Gy was associated with approximately 2.6 times increased Grade 3 or greater chronic toxicity. Conclusions Our results suggest IMRT-based CRT with concurrent fluoropyrimidine and cisplatin is a safe and feasible option for patient with SCCA and may cause less acute toxicity. The role for radiation dose escalation is unclear and requires further study.

Lower socioeconomic status (SES) is associated with shorter overall survival (OS) in patients with locoregional colon cancer. We aimed to estimate: (1) the proportion of SES-based OS disparities mediated by disparities in the quality and location of surgical treatment in patients with resected stage I–III colon cancer and (2) the relative importance of components of surgical quality. We examined patients ages 18–80 years with resected stage I–III colon adenocarcinoma using the 2010–2016 National Cancer Database. SES was defined at the zip code level. Inverse odds weighting mediation analysis was used to estimate the proportion mediated (PM) for nine treatment quality-related and facility-related factors and composite PMs in models including all nine mediators. Models compared high SES patients with each lower SES stratum. Among 171,009 patients, 5-year OS increased from 70.4% in low SES patients to 78.1% in high SES. When high SES patients were compared with low, lower-middle, and upper-middle SES patients, PM ranges among lower SES strata were: minimally invasive surgery 16.0–16.6%, lymph nodes examined 7.7–9.6%, positive margins 3.8–6.5%, length of stay 16.7–28.1%, readmissions insignificant to 3.7%, treatment at > 1 CoC facility 2.7–3.1%, facility type insignificant to 7.3%, facility volume 2.9–8.2%, and adjusted facility 90-day mortality rates 33.2–42.8%. Composite PMs were 76.9% (95% CI 61.3%, 92.4%) for low SES, 68.7% (95% CI 56.4%, 81.1%) for lower-middle SES, and 60.9% (95% CI 43.1%, 78.6%) for upper-middle SES. These data suggest that improving the quality of the surgical episode for disadvantaged patients undergoing resection for locoregional colon cancer could decrease SES-based survival disparities by over half.

Background The impact of molecular aberrations on survival after resection of colorectal liver metastases (CLM) in patients with early-age-onset (EOCRC) versus late-age-onset colorectal cancer (LOCRC) is unknown. Methods Patients who underwent liver resection for CLM with known RAS, BRAF and MSI status were retrospectively studied. The prognostic impact of RAS mutations by age was analysed with age as a categorical variable and a continuous variable. Results The study included 573 patients, 192 with EOCRC and 381 with LOCRC. The younger the age of onset of CRC, the greater the negative impact on overall survival of RAS mutations in the LOCRC, EOCRC, and ≤40 years (hazard ratio (HR), 1.64 (95% confidence interval (CI), 1.23–2.20), 2.03 (95% CI, 1.30–3.17), and 2.97 (95% CI, 1.44–6.14), respectively. Age-specific mortality risk and linear regression analysis also demonstrated that RAS mutations had a greater impact on survival in EOCRC than in LOCRC (slope: −4.07, 95% CI −8.10 to 0.04, P = 0.047, R2 = 0.08). Conclusion Among patients undergoing CLM resection, RAS mutations have a greater negative influence on survival in patients with EOCRC, more so in patients ≤40 years, than in patients with LOCRC and should be considered as a prognostic factor in multidisciplinary treatment planning.

The objectives of this expert review are: (1) to prepare clinicians to recognize the presentation and evidence-based risk factors for young adult-onset colorectal cancer (CRC), defined as CRC diagnosed in individuals 18 -50 years of age; (2) to improve management for patients with young onset CRC. This review will focus on the following topics relevant to young adult-onset CRC: epidemiology and risk factors; clinical presentation; diagnostic and therapeutic management including options for colorectal and extra-colonic surgical intervention, chemotherapy and immune-oncology therapies; genetic testing and its potential impact on preimplantation genetics; fertility preservation; and cancer surveillance recommendations for these individuals and their family members.The evidence reviewed in this manuscript is a summation of relevant scientific publications, expert opinion statements, and current practice guidelines. BEST PRACTICE ADVICE 1: With the rising incidence of people developing CRC before 50 years of age, diagnostic evaluation of the colon and rectum is encouraged for all patients, irrespective of age, who present with symptoms that may be consistent with CRC, including but not limited to: rectal bleeding, weight loss, change in bowel habit, abdominal pain, iron deficiency anemia. BEST PRACTICE ADVICE 2: Clinicians should obtain family history of colorectal and other cancers in first and second degree relatives of patients with young adult-onset CRC and discuss genetic evaluation with germline genetic testing either in targeted genes based on phenotypic presentation or in multiplex gene panels regardless of family history. BEST PRACTICE ADVICE 3: Clinicians should present the role of fertility preservation prior to cancer-directed therapy including surgery, pelvic radiation, or chemotherapy BEST PRACTICE ADVICE 4: Clinicians should counsel patients on the benefit of germline genetic testing and familial cancer panel testing in the pre-surgical period to inform which surgical options may be available to the patient with young adult-onset CRC BEST PRACTICE ADVICE 5: Clinicians should consider utilizing germline and somatic genetic testing results to inform chemotherapeutic strategies BEST PRACTICE ADVICE 6: Clinicians should offer hereditary CRC syndrome specific screening for CRC and extra-colonic cancers only to young adult-onset CRC patients who have a genetically or clinically diagnosed hereditary CRC syndrome. For patients with sporadic young adult-onset CRC, extra-colonic screening and CRC surveillance intervals are the same as for patients with older adult-onset CRC.

Colorectal cancer in the young adult population is of increasing incidence and concern. Genetic predisposition and heritable syndromes contribute to this trend, but perhaps more concerning is the majority of new diagnoses that involve no traceable genetic risk factors. Prevention and early recognition, with a high suspicion in the symptomatic young adult, are critical in attenuating recent trends. Clinical management requires coordinated multidisciplinary care from diagnosis to surveillance in order to ensure appropriate management. This review provides a summary of key aspects related to colorectal cancer in adolescents and young adults, including epidemiology, biology, genetics, clinical management, and prevention.

Curative-intent surgical resection of colon cancer involves optimal approaches to the peri-tumoral tissue, the mesocolon, and the draining lymph nodes. The key corresponding concepts that will be discussed are complete mesocolic excision (CME), central vascular ligation (CVL) or D3 dissection, and circumferential resection margin (CRM). We aim to describe these techniques and delineate evidence surrounding their technical feasibility, pathologic detail, as well as long-term oncologic impact. CME with CVL and D3 dissection are overlapping concepts both emphasizing anatomy-based resection of tumor and regional lymph nodes that does not breach the embryonic visceral fascia and ensures complete lymph node dissection up to the mesenteric root. Completeness of the mesocolic plane, number of harvested nodes, and CRM are surgical pathologic parameters that impact oncologic outcome. Attention to these details has been associated with improved outcomes in retrospective observational trials and the choice of open or minimally invasive approaches must be determined by surgeon's technical experiences.

Background While the prognostic implications of positive circumferential resection margins (CRM) have been established for rectal cancer, its significance in colon cancer has not been well defined. The aim of the current study was to determine national rates for positive CRM in locally advanced colon cancer, associated factors, and survival impact. Methods The National Cancer Database was queried to identify patients with stage II-III adenocarcinoma of the colon (2004-2015). Results Positive CRM was identified in 9% of stage II and 12% of stage III patients. Factors associated with negative CRM included surgery in a high-volume facility, adequate lymph-node harvest, and negative distal/proximal margins. No difference in CRM rates was observed between surgical approaches, although having a positive CRM was significantly associated with higher conversion rates. Positive CRM was associated with significantly lower overall survival on both univariate and multivariable analysis. Conclusions Positive CRM rates exceeded 10% nationally and have an adverse impact on survival. While several tumor characteristics were identified as independent risk factors, oncologic resections and surgery at high-volume centers were associated with lower rates of positive CRM. These findings emphasize the need for process improvement initiatives targeting modifiable factors, including adoption of appropriate oncologic techniques, standardized pathology reporting, and potential neoadjuvant strategies.

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 14(th), 2018. In total, 1,060 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.

PURPOSE To develop recommendations for duration of adjuvant chemotherapy with a fluoropyrimidine and oxaliplatin for patients with completely resected stage III colon cancer based on the results of trials of 3 months compared with 6 months of treatment. METHODS ASCO convened an Expert Panel and conducted a systematic review of relevant studies. The guideline recommendations were based on the review of evidence by the Expert Panel. RESULTS Pooled data from the six International Duration Evaluation of Adjuvant Chemotherapy (IDEA) Collaboration randomized controlled trials comprise the evidence base for these guideline recommendations. RECOMMENDATIONS The recommendations for therapy duration apply to patients with completely resected stage III colon cancer who are being offered adjuvant chemotherapy with oxaliplatin and a fluoropyrimidine. Recommendations are informed by the findings of a recent pooled analysis of clinical trials that compared 6 months versus 3 months of oxaliplatin-based chemotherapy. For patients at a high risk of recurrence (T4 and/or N2), adjuvant chemotherapy should be offered for a duration of 6 months. For patients at a low risk of recurrence (T1, T2, or T3 and N1), either 6 months of adjuvant chemotherapy or a shorter duration of 3 months may be offered on the basis of a potential reduction in adverse events and no significant difference in disease-free survival with the 3-month regimen. In determining duration of therapy, the Expert Panel recommends a shared decision-making approach, taking into account patient characteristics, values and preferences, and other factors and including a discussion of the potential for benefit and risks of harm associated with treatment duration. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines .

Genomic profiling of colorectal cancer aims to identify actionable somatic mutations but can also discover incidental germline findings.The purpose of this study was to report the detection of pathogenic germline variants that confer heritable cancer predisposition.This was a retrospective study.The study was conducted at a tertiary-referral institution.Between 2012 and 2015, 1000 patients with advanced cancer underwent targeted exome sequencing of a 202-gene panel. The subgroup of 151 patients with advanced colorectal cancer who underwent matched tumor-normal (blood) sequencing formed our study cohort.Germline variants in 46 genes associated with hereditary cancer predisposition were classified according to a defined algorithm based on in silico predictions of pathogenicity. Patients with presumed pathogenic variants were examined for type of mutation, as well as clinical, pedigree, and clinical genetic testing data.We measured detection of pathogenic germline variants.A total of 1910 distinct germline variants were observed in 151 patients. After filtering, 15 pathogenic germline variants (9.9%) were found in 15 patients, arising from 9 genes of varying penetrance for colorectal cancer (APC (n = 2; 13%), ATM (n = 1; 6%), BRCA1 (n = 2; 13%), CDH1 (n = 2; 13%), CHEK2 (n = 4; 27%), MSH2 (n = 1; 7%), MSH6 (n = 1; 7%), NF2 (n = 1; 7%), and TP53 (n = 1; 7%)). Patients with pathogenic variants were diagnosed at a younger age than those without (median, 45 vs 52 y; p = 0.03). Of the 15 patients, 7 patients (46.7%) with variants in low/moderate- penetrant genes for colorectal cancer would likely have not been tested based on clinical and pedigree criteria, where 2 harbored clinically actionable variants (CDH1 and NF2, 28.5% of 7).This study was limited by its small sample size and advanced-stage patients.Tumor-normal sequencing can incidentally discover clinically unsuspected germline variants that confer cancer predisposition in 9.9% of patients with advanced colorectal cancer. Precision medicine should integrate clinical cancer genetics to inform and interpret the actionability of germline variants and to provide follow-up care to mutation carriers. See Video Abstract at http://links.lww.com/DCR/A906.

Objective Patients with Lynch syndrome (LS) are at markedly increased risk for colorectal cancer. It is being increasingly recognised that the immune system plays an essential role in LS tumour development, thus making an ideal target for cancer prevention. Our objective was to evaluate the safety, assess the activity and discover novel molecular pathways involved in the activity of naproxen as primary and secondary chemoprevention in patients with LS. Design We conducted a Phase Ib, placebo-controlled, randomised clinical trial of two dose levels of naproxen sodium (440 and 220 mg) administered daily for 6 months to 80 participants with LS, and a co-clinical trial using a genetically engineered mouse model of LS and patient-derived organoids (PDOs). Results Overall, the total number of adverse events was not different across treatment arms with excellent tolerance of the intervention. The level of prostaglandin E2 in the colorectal mucosa was significantly decreased after treatment with naproxen when compared with placebo. Naproxen activated different resident immune cell types without any increase in lymphoid cellularity, and changed the expression patterns of the intestinal crypt towards epithelial differentiation and stem cell regulation. Naproxen demonstrated robust chemopreventive activity in a mouse co-clinical trial and gene expression profiles induced by naproxen in humans showed perfect discrimination of mice specimens with LS and PDOs treated with naproxen and control. Conclusions Naproxen is a promising strategy for immune interception in LS. We have discovered naproxen-induced gene expression profiles for their potential use as predictive biomarkers of drug activity. Trial registration number gov Identifier: NCT02052908

An increasing number of studies are describing potential uses of circulating tumour DNA (ctDNA) in the care of patients with colorectal cancer. Owing to this rapidly developing area of research, the Colon and Rectal–Anal Task Forces of the United States National Cancer Institute convened a panel of multidisciplinary experts to summarize current data on the utility of ctDNA in the management of colorectal cancer and to provide guidance in promoting the efficient development and integration of this technology into clinical care. The panel focused on four key areas in which ctDNA has the potential to change clinical practice, including the detection of minimal residual disease, the management of patients with rectal cancer, monitoring responses to therapy, and tracking clonal dynamics in response to targeted therapies and other systemic treatments. The panel also provides general guidelines with relevance for ctDNA-related research efforts, irrespective of indication., The analysis of ctDNA obtained from low-volume blood samples has the potential to transform the management of patients with colorectal cancer. Nevertheless, research priorities and minimum standards for sample collection and analysis in this area are currently missing. In this Position Paper, the NCI Colon and Rectal–Anal Task Forces provide a set of recommendations designed to address these challenges and accelerate the implementation of ctDNA in the management of patients with colorectal cancer.

In patients with stage IV colorectal cancer (CRC), minimally invasive surgery (MIS) may offer optimal oncologic outcome with low morbidity. However, the relative benefit of MIS compared to open surgery in patients requiring multistage resections has not been evaluated.Patients who underwent totally minimally invasive (TMI) or totally open (TO) resections of CRC primary and liver metastases (CLM) in 2009-2016 were analyzed. Inverse probability of weighted adjustment by propensity score was performed before analyzing risk factors for complications and survival.The study included 43 TMI and 121 TO patients. Before and after adjustment, TMI patients had significantly less cumulated postoperative complications (41% vs. 59%, p = 0.001), blood loss (median 100 vs. 200 ml, p = 0.001) and shorter length of hospital stay (median 4.5 vs. 6.0 days, p0.001). Multivariate analysis identified TO approach vs. MIS (OR = 2.4, p0.001), major liver resection (OR = 4.4, p0.001), and multiple CLM (OR = 2.3, p = 0.001) as independent risk factors for complications. 5-year overall survival was comparable (81% vs 68%, p = 0.59).In patients with CRC undergoing multistage surgical treatment, MIS resection contributes to optimal perioperative outcomes without compromise in oncologic outcomes.

Importance Total neoadjuvant therapy (TNT) is often used to downstage locally advanced rectal cancer (LARC) and decrease locoregional relapse; however, more than one-third of patients develop recurrent metastatic disease. As such, novel combinations are needed. Objective To assess whether the addition of pembrolizumab during and after neoadjuvant chemoradiotherapy can lead to an improvement in the neoadjuvant rectal (NAR) score compared with treatment with FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) and chemoradiotherapy alone. Design, setting, and participants In this open-label, phase 2, randomized clinical trial (NRG-GI002), patients in academic and private practice settings were enrolled. Patients with stage II/III LARC with distal location (cT3-4 ≤ 5 cm from anal verge, any N), with bulky disease (any cT4 or tumor within 3 mm of mesorectal fascia), at high risk for metastatic disease (cN2), and/or who were not candidates for sphincter-sparing surgery (SSS) were stratified based on clinical tumor and nodal stages. Trial accrual opened on August 1, 2018, and ended on May 31, 2019. This intent-to-treat analysis is based on data as of August 2020. Interventions Patients were randomized (1:1) to neoadjuvant FOLFOX for 4 months and then underwent chemoradiotherapy (capecitabine with 50.4 Gy) with or without intravenous pembrolizumab administered at a dosage of 200 mg every 3 weeks for up to 6 doses before surgery. Main outcomes and measures The primary end point was the NAR score. Secondary end points included pathologic complete response (pCR) rate, SSS, disease-free survival, and overall survival. This report focuses on end points available after definitive surgery (NAR score, pCR, SSS, clinical complete response rate, margin involvement, and safety). Results A total of 185 patients (126 [68.1%] male; mean [SD] age, 55.7 [11.1] years) were randomized to the control arm (CA) (n = 95) or the pembrolizumab arm (PA) (n = 90). Of these patients, 137 were evaluable for NAR score (68 CA patients and 69 PA patients). The mean (SD) NAR score was 11.53 (12.43) for the PA patients (95% CI, 8.54-14.51) vs 14.08 (13.82) for the CA patients (95% CI, 10.74-17.43) (P = .26). The pCR rate was 31.9% in the PA vs 29.4% in the CA (P = .75). The clinical complete response rate was 13.9% in the PA vs 13.6% in the CA (P = .95). The percentage of patients who underwent SSS was 59.4% in the PA vs 71.0% in the CA (P = .15). Grade 3 to 4 adverse events were slightly increased in the PA (48.2%) vs the CA (37.3%) during chemoradiotherapy. Two deaths occurred during FOLFOX: sepsis (CA) and pneumonia (PA). No differences in radiotherapy fractions, FOLFOX, or capecitabine doses were found. Conclusions and relevance Pembrolizumab added to chemoradiotherapy as part of total neoadjuvant therapy was suggested to be safe; however, the NAR score difference does not support further study. Trial registration ClinicalTrials.gov Identifier: NCT02921256.

PURPOSE: Patients with Lynch syndrome (LS) have a significantly elevated lifetime risk of developing biliary tract cancers (BTCs) compared to the general population. However, few studies have characterized the clinical characteristics, genetic features, or long-term outcomes of mismatch-repair deficient (dMMR) cholangiocarcinomas associated with LS. METHODS: A retrospective review of a prospectively maintained Familial High-Risk GI Cancer Clinic database identified all patients with BTCs evaluated from 2006 to 2016 who carried germline mutations in MLH1, MSH2, MSH6, or PMS2. RESULTS: Eleven patients with BTCs were identified: four perihilar, four intrahepatic, one extrahepatic, one gallbladder, and one ampulla of Vater. All patients had underlying germline mutations and a personal history of a LS-associated malignancy, most commonly (63.3%) colorectal cancer. Ten (90.9%) patients were surgically explored, and margin negative resection was possible in seven (63.3%). Chemotherapy (90.9%) and/or chemoradiation (45.5%) was administered to most patients. Among the seven patients presenting with non-metastatic disease who underwent surgical resection with curative intent, the 5-year overall survival rate was 53.3%. The median overall survival for the four patients not treated with curative intent was 17.2 months. CONCLUSIONS: dMMR biliary tract cancers associated with LS are rare but long-term outcomes may be more favorable than contemporaneous cohorts of non-Lynch-associated cholangiocarcinomas. Given the emerging promise of immunotherapy for patients with dMMR malignancies, tumor testing for dMMR followed by confirmatory germline testing should be considered in patients with BTC and a personal history of other LS cancers.

Purpose: Determination of microsatellite instability (MSI) by PCR is the gold standard; however, IHC of mismatch repair (MMR) proteins is frequently performed instead. The reliability of these methods on postneoadjuvant therapy specimens is unknown. We examined the effect of neoadjuvant therapy on MSI results by PCR and IHC. Experimental design: A total of 239 colorectal cancers resected after neoadjuvant therapy were assessed for MSI with PCR and IHC. PCR and IHC results for matched paired pre- and posttreatment specimens were compared. In parallel, 2 isogenic cell lines conditioned for MMR functioning and 2 different patient-derived xenografts (PDXs) were exposed to chemotherapy, radiation, or both. We also examined whether establishment of PDXs induced MSI changes in 5 tumors. IHC and MSI were tested after treatment to assess for changes. Results: We identified paired pre- and posttreatment specimens for 37 patients: 2 with PCR only, 34 with IHC only, and 1 with both. All 3 patients with PCR had microsatellite stable pre- and posttreatment specimens. Of the 35 patients with IHC, 30 had intact MMR proteins in pre- and posttreatment specimens, 1 had equivocal MLH1 staining in the pretreatment and loss in the posttreatment specimen, and 4 had intact pretreatment MSH6 but variable posttreatment staining. In the experimental setting, no changes in MSI status were detected after treatment or tumor implantation in animals. Conclusions: Our findings show that the expression of MMR proteins, commonly MSH6, can change after neoadjuvant therapy and confirm PCR as the gold-standard test for MSI after neoadjuvant therapy. Clin Cancer Res; 23(17); 5246–54. ©2017 AACR.

Squamous cell carcinoma (SCC) of the rectum is a rare disease with

The American Society of Colon and Rectal Surgeons is dedicated to ensuring high-quality patient care by advancing the science, prevention, and management of disorders and diseases of the colon, rectum, and anus. The Clinical Practice Guidelines Committee is composed of Society members who are chosen

Background Chemotherapy is associated with postoperative ventral incisional hernia (PVIH) after right hemicolectomy (RHC) for colon cancer, and abdominal wall closure technique may affect PVIH. We sought to identify clinical predictors of PVIH. Methods We retrospectively analyzed patients who underwent RHC for colon cancer from 2008-2018 and later developed PVIH. Time to PVIH was analyzed with Kaplan-Meier analysis, clinical predictors were identified with multivariable Cox proportional hazards modeling, and the probability of PVIH given chemotherapy and the suture technique was estimated with Bayesian analysis. Results We identified 399 patients (209 no adjuvant chemotherapy and 190 adjuvant chemotherapy), with an overall PVIH rate of 38%. The 5-year PVIH rate was 55% for adjuvant chemotherapy, compared with 38% for none (log-rank P < .05). Adjuvant chemotherapy (hazard ratio [HR] 1.65, 95% confidence interval [CI] 1.18-2.31, P < .01), age (HR .99, 95% CI .97-1.00, P < .01), body mass index (HR 1.02, 95% CI 1.00-1.04, P < .01), and neoadjuvant chemotherapy (HR 1.92, 95% CI 1.21-3.00, P < .01) were independently associated with PVIH. Postoperative ventral incisional hernia was more common overall in patients who received adjuvant chemotherapy (46% compared with 30%, P < .01). In patients who received adjuvant chemotherapy, the probability of PVIH for incision closure with #1 running looped polydioxanone was 42%, compared with 59% for incision closure with #0 single interrupted polyglactin 910. Discussion Exposure to chemotherapy increases the probability of PVIH after RHC, and non–short stitch incision closure further increases this probability, more so than age or body mass index. The suture technique deserves further study as a modifiable factor in this high-risk population.

Background Current evidence supports the curative resection of colorectal cancer and synchronous liver and lung metastases in selected patients.1,2 This video shows simultaneous left colectomy, bilobar liver resection, and lung metastasectomy via a transdiaphragmatic approach for stage IV colorectal cancer.3 PATIENT: A 57-year-old man with a stage IV colonic adenocarcinoma was considered for simultaneous resection of primary, liver, and lung metastases without thoracic incision. The tumor mutational status was KRAS, NRAS, and BRAF wild-type, and the patient underwent preoperative chemotherapy. Technique After performing a midline laparotomy, atypical liver resection of segments 8/4a was performed under the guidance of intraoperative ultrasonography and intermittent Pringle maneuver using the two-surgeon's technique. A small capsular lesion in segment 3 also was intraoperatively detected and resected. Lung metastasectomy of the right lower lobe was performed via a transdiaphragmatic approach using an endoscopic stapler. Sigmoid colectomy with transanal circular-stapled anastomosis was performed. Duration of surgery and blood loss were 358 min and 400 ml, respectively. Histopathological examination showed metastatic colonic adenocarcinoma with negative surgical margins and final stage was T3N2aM1b. The patient was discharged on postoperative day 6 without complication. He was alive and free of disease at 90-day follow-up. Conclusions Simultaneous colon, liver, and lung resection via a transdiaphragmatic approach is a feasible and safe surgical strategy in selected patients with peripheral lung metastases and favorable tumor biology.4 This surgical strategy avoids thoracic incision, multiple operations, and may reduce the healthcare costs and the recovery time to early implement postoperative therapy.

Advancements in clinical practice usually require level one evidence from clinical trials that directly compare new approaches to standard of care. While clinical trials have provided data to guide advances in practices across surgical oncology, all too often accrual to clinical trials is slower than anticipated, and once results are presented and published, adoption in clinical practice is slow. Why and how can surgeons be successfully involved with clinical trials? An expert panel discusses the basic infrastructure of clinical trials, investigator-initiated trials, the National Clinical Trials Network, and opportunities for surgeon involvement. Two national clinical trials, NSABP B-51/RTOG 1304 and PROSPECT N1048, are discussed to highlight the role of the surgical oncologist.

Several factors can affect the risk of recurrence after curative resection of colorectal cancer (CRC). We aimed to develop a risk model for recurrence after definitive treatment of Stage I-III CRC using data from a nationally representative database and to develop an individualized web-based risk calculator.A random sample of patients who underwent resection for Stage I-III CRC between 2006 and 2007 at Commission on Cancer (CoC) accredited centers were included. Primary data regarding first recurrence was abstracted from medical records and merged with the National Cancer Database. Multivariable cox regression analysis was used to test for factors associated with cancer recurrence, stratified by stage. Model performance was tested by c statistic and calibration plots. Hazard Ratios were utilized to develop an individualized web-based recurrence prediction tool.A total of 8249 patients from 1175 CoC centers were included. Of these, 1656 (20.1%) patients had a recurrence during 5 years of follow-up. Median time to recurrence was 16 months. The final predictive models displayed excellent discrimination and calibration with concordance indexes of 0.7. The online calculator included 12 variables, including tumor site, stage, time since surgery, and surveillance intensity. Output is displayed numerically and graphically with an icon array.Using primarily abstracted recurrence data from a random sample of patients treated for CRC at CoC accredited centers across the United States, we successfully created an individualized CRC recurrence risk assessment tool. This web-based calculator can be used by physicians and patients in shared decision making to guide management discussions.ClinicalTrials.gov Registration Number: NCT02217865.

Background Circumferential resection margin (CRM) status is an important predictor of outcomes after rectal cancer operation, and is influenced not only by operative technique, but also by incorporation of a multidisciplinary treatment strategy. This study sought to develop a risk-adjusted quality metric based on CRM status to assess hospital-level performance for rectal cancer operation. Study Design We conducted a retrospective observational cohort study of 58,374 patients with resected stage I to III rectal cancer within 1,303 hospitals who were identified from the National Cancer Database (2010 to 2015). The number of observed cases with a positive CRM (≤ 1 mm) was divided by the risk-adjusted expected number of cases with positive CRM to form the observed-to-expected (O/E) ratio. Secondary endpoint was overall survival. Results The overall rate of CRM positivity was 15.9%. Based on the O/E ratio for 1,139 hospitals, 147 (12.9%) and 103 (9.0%) were significantly worse and better performers, respectively. The majority of hospitals (n = 570) performed as expected. Positive CRMs using criteria of 0 mm and 0.1 to 1 mm were associated with a significantly shorter 5-year overall survival of 49% and 63.5% (hazard ratio 1.67; 95% CI, 1.57 to 1.76 and hazard ratio 1.19; 95% CI, 1.12 to 1.26) than negative CRM > 1 mm of 74.1% (all p Conclusions CRM-based O/E ratio is a robust hospital-based quality measure for rectal cancer operation. It allows facilities to compare their performance with that of centers of similar characteristics and helps identify underperforming, at-risk, and high-performing centers. National quality-improvement initiatives for rectal cancer should focus on ensuring high-quality data collection and providing ready access to risk-adjusted comparative metrics.

Despite the use of neoadjuvant chemoradiation and total mesorectal excision for rectal cancer, lateral pelvic lymph node recurrence is still an important problem.This study aimed to determine the indication for lateral pelvic lymph node dissection in post neoadjuvant chemoradiation rectal cancer.This is a retrospective analysis of a prospectively collected institutional database.This study was conducted at a tertiary care cancer center from January 2006 through December 2017.Patients who had rectal cancer with suspected lateral pelvic lymph node metastasis, who underwent total mesorectal excision with lateral pelvic lymph node dissection, were included.The primary outcome measured was pathologic lateral pelvic lymph node positivity.The associations between lateral pelvic lymph node size on post-neoadjuvant chemoradiation imaging and pathologic lateral pelvic lymph node positivity and recurrence outcomes were evaluated.A total of 64 patients were analyzed. The mean lateral pelvic lymph node size before and after neoadjuvant chemoradiation was 12.6 ± 9.5 mm and 8.5 ± 5.4 mm. The minimum size of positive lateral pelvic lymph node was 5 mm on post neoadjuvant chemoradiation imaging. Among 13 (20.3%) patients who had a5 mm lateral pelvic lymph node after neoadjuvant chemoradiation, none were pathologically positive. Among 51 (79.7%) patients who had a ≥5 mm lateral pelvic lymph node after neoadjuvant chemoradiation, 33 patients (64.7%) were pathologically positive. Five-year overall survival and disease-specific survival were higher in the histologic lateral pelvic lymph node negative group than in the lateral pelvic lymph node positive group (overall survival 79.6% vs 61.8%, p = 0.122; disease-specific survival 84.5% vs 66.2%, p= 0.088). After a median 39 months of follow-up, there were no patients in the5 mm group who died of cancer. There were no lateral compartment recurrences in the entire cohort.Being a single-center retrospective study may limit generalizability.Post-neoadjuvant chemoradiation lateral pelvic lymph node size ≥5 mm was strongly associated with pathologic positivity. No patients with size5 mm had pathologically positive lymph nodes. Following lateral pelvic lymph node dissection, no patients with a positive lateral pelvic lymph node developed lateral compartment recurrence. Therefore, patients who have rectal cancer with clinical evidence of lateral pelvic lymph node metastasis and post-neoadjuvant chemoradiation lateral pelvic lymph node size ≥5 mm should be considered for lateral pelvic lymph node dissection at the time of total mesorectal excision. See Video Abstract at http://links.lww.com/DCR/B3. ¿QUIéN DEBE RECIBIR LINFADENECTOMíA PéLVICA LATERAL DESPUéS DE LA QUIMIORRADIACIóN NEOADYUVANTE?: A pesar del uso de quimiorradiación neoadyuvante y la escisión total de mesorectao para el cáncer de recto, la recurrencia en los ganglios linfáticos pélvicos laterales sigue siendo un problema importante.Determinar la indicación para la disección de los ganglios linfáticos pélvicos laterales en el cáncer rectal post quimiorradiación neoadyuvante. DISEÑO:: Análisis retrospectivo de la base de datos institucional prospectivamente recopilada.Centro de cáncer de atención terciaria, de enero de 2006 hasta diciembre de 2017.Pacientes con cáncer de recto con sospecha de metástasis en los ganglios linfáticos pélvicos laterales, que se sometieron a escisión total mesorectal con disección de los ganglios linfáticos pélvicos laterales.Positividad de ganglios linfáticos pélvicos laterales en histopatología.Se evaluaron las asociaciones entre el tamaño de los ganglios linfáticos pélvicos laterales en imagenología postquimiorradiación neoadyuvante y la positividad y recurrencia en los ganglios linfáticos pélvicos laterales en histopatología.Se analizaron un total de 64 pacientes. La media del tamaño de los ganglios linfáticos pélvicos laterales antes y después de la quimiorradiación neoadyuvante fue de 12.6 ± 9.5 mm y 8.5 ± 5.4 mm, respectivamente. El tamaño mínimo de los ganglios linfáticos pélvicos laterales positivos fue de 5 mm en las imágenes postquimiorradiación neoadyuvante. Entre 13 (20.3%) pacientes que tenían5 mm de ganglio linfático lateral pélvico después de la quimiorradiación neoadyuvante; ninguno fue positivo en histopatología. Entre 51 (79.7%) pacientes con ganglio linfático pélvico lateral ≥ 5 mm después de la quimiorradiación neoadyuvante; 33 pacientes (64.7%) fueron positivos en histopatología. La supervivencia general a 5 años y la supervivencia específica de la enfermedad fueron mayores en el grupo histológico de ganglio linfático pélvico lateral negativo que en el grupo de ganglio linfático pélvico lateral positivo (Supervivencia general 79.6% vs 61.8%, p = 0.122; Supervivencia específica de la enfermedad 84.5% vs 66.2%, p = 0.088). Después de una mediana de seguimiento de 39 meses, no hubo pacientes en el grupo de5 mm que hayan fallecido por cáncer. No hubo recurrencias en el compartimento lateral en toda la cohorte.Al ser un estudio retrospectivo en un solo centro puede limitar la generalización.El tamaño de los ganglios linfáticos pélvicos laterales postquimiorradiación neoadyuvante ≥ 5 mm se asoció fuertemente con la positividad histopatológica. Ningún paciente con tamaño5 mm tuvo ganglios linfáticos histopatológicamente positivos. Después de la disección de los ganglios linfáticos pélvicos laterales, ningún paciente con ganglios linfáticos pélvicos laterales positivos desarrolló recurrencia del compartimiento lateral. Por lo tanto, los pacientes con cáncer rectal con evidencia clínica de metástasis en los ganglios linfáticos pélvicos laterales y tamaño de ganglios linfáticos pélvicos laterales postquimiorradiación neoadyuvante ≥ 5 mm deben considerarse para disección de los ganglios linfáticos pélvicos laterales en el momento de la escisión total de mesorrecto. Vea el Abstract en video en http://links.lww.com/DCR/B3.

Currently, colorectal cancers accounted for the second-highest number of cancer deaths in the US. Hereditary syndromes, strong family history, and inflammatory bowel disease are all conditions that confer predisposition risks. In hereditary syndromes, screening must be more frequent and start earlier. With familial risk, screening should depend on the age of cancer onset and number of affected relatives. For inflammatory bowel disease, surveillance should depend on duration, severity, and extent of colitis.

Background Magnetic resonance imaging (MRI) is essential for the multidisciplinary treatment of rectal cancer. However, baseline experience of surgical residents with MRI is unknown. Therefore, a needs assessment survey was conducted to examine confidence with pelvic MRI for residents entering Complex General Surgical Oncology (CSGO) fellowships. Methods A multi-institutional survey evaluated incoming CGSO fellows’ experience with pelvic MRI for rectal cancer in residency. Additionally, confidence was assessed for essential components of pelvic MRI including T- and N-stage, circumferential resection margin (CRM), extramural venous invasion (EMVI), and pelvic anatomy. Results Of the twenty-four incoming fellows who completed the survey (response rate = 44%), 20 reported frequent use of pelvic MRI for rectal cancer in residency, but 16 reported rarely/never interpreting images themselves for staging or operative planning. Most respondents reported low confidence for T-stage, N-stage, CRM, EMVI, as well as pelvic anatomy, particularly for lateral and posterior pelvis. Conclusions The development of a pelvic MRI curriculum for residents entering CGSO fellowships could enhance their clinical training in the multidisciplinary management of patients with rectal cancer.

Traditional germline sequencing and deletion/duplication analysis does not detect Lynch syndrome-causing mutations in all individuals whose colorectal or endometrial tumors demonstrate mismatch repair (MMR) deficiency. Unique inversions and other rearrangements of the MMR genes have been reported in families with Lynch syndrome. In 2014, a recurrent inversion of MSH2 exons 1-7 was identified in five families suspected to have Lynch syndrome. We aimed to describe our clinical experience in identifying families with this specific inversion. Four probands whose Lynch syndrome-associated tumors demonstrated absence of MSH2/MSH6 staining and who had negative MMR germline testing were evaluated for the MSH2 inversion of exons 1-7, offered during initial genetic workup or upon routine clinical follow-up. All four probands tested positive for the MSH2 inversion. Proband cancer diagnoses included colon and endometrial adenocarcinoma and sebaceous adenoma. A variety of Lynch syndrome-associated cancers were reported in the family histories, although only one family met Amsterdam II criteria. Thirteen at-risk relatives underwent predictive testing. MSH2 inversion of exons 1-7 was found in four probands previously suspected to have Lynch syndrome based on family history and tumor testing. This testing should be offered routinely to patients with tumors demonstrating loss of MSH2/MSH6 staining.

Constitutional mismatch repair deficiency syndrome (CMMRD) is a rare autosomal recessive predisposition to colorectal polyposis and other malignancies, often childhood-onset, that is caused by biallelic inheritance of mutations in the same mismatch repair gene. Here, we describe a patient with a clinical diagnosis of CMMRD based on colorectal polyposis and young-onset endometrial cancer who was identified to have two alterations in trans in PMS2: one known pathogenic mutation (c.1831insA; p.Ile611Asnfs*2) and one novel variant of uncertain significance (c.505C>G; p.Arg169Glu), a missense alteration. We describe the clinical and molecular features in the patient harboring this novel alteration c.505C>G, who meets clinical criteria for CMMRD and exhibits molecular evidence supporting a diagnosis of CMMRD. Although experimental validation is needed to confirm its pathogenicity, PMS2 c.505C>G likely has functional consequences that contributes to our patient's phenotype based on the patient's clinical presentation, tumor studies, and bioinformatics analysis.

Surgery for locally advanced rectal cancers beyond the plane of total mesorectal excision (TME) or extramesorectal nodal involvement should include complete resection. This study evaluated the oncologic feasibility and safety of robot-assisted surgery for rectal cancer beyond the TME plane.The study analyzed the operative, perioperative, and oncologic outcomes for all patients who underwent robot-assisted extended rectal cancer surgery from April 2009 to February 2015.Of 36 patients, 22 underwent multivisceral en bloc resection, and 18 underwent extramesorectal lymph node (EMRLN) dissection. The median tumor location was 5 cm [interquartile range (IQR), 2.2-9.0 cm] from the anal verge. A total of 32 patients underwent neoadjuvant chemoradiation therapy. The median body mass index of the patients was 26.8 kg/m(2) (IQR, 24.0-31.9 kg/m(2)). Conversion was required for one patient because of inability to tolerate the Trendelenburg position. All the resections were R0, and there were no incomplete TMEs. The vagina and prostate or periprostatic structures were the most commonly resected (n = 13/22), and the lateral pelvic nodes were the most common EMRLNs (n = 16/18). The median numbers of examined mesorectal lymph nodes and EMRLNs were respectively 20 (IQR, 18.0-28.0) and 2.5 (IQR, 1.0-6.0). The median hospital stay was 4 days (IQR, 3.0-5.5 days). Six patients experienced Clavien-Dindo grade 3 complications, the most common of which was deep abscess (n = 5, 13.8 %). The 5-year actuarial local recurrence rate was 3.6 %.Minimally invasive resection for rectal cancer can be performed with extended lymph node dissection or en bloc multivisceral resection using the surgical robot in selected patients. This technique is feasible and has acceptable morbidity.

Patients with germline DNA mismatch repair deficiency (dMMR) have an increased risk of gastric cancer. From our institutional database, we identified 12 patients with germline dMMR gastric cancer. Ten patients (83%) underwent surgical resection, with a 5-year overall survival rate of 88%. None of the three patients who received preoperative therapy and five patients with recurrent or metastatic disease experienced a significant response to 5-fluorouracil-based chemotherapy.

Robotic surgery is increasingly performed for low rectal cancer.1 A redundant sigmoid colon makes retraction and pelvic dissection challenging. We present a ‘pelvis-first’ approach to robotic proctectomy where pelvic dissection occurs prior to colonic mobilization. A 26-year-old woman was diagnosed with a clinical T3N1 rectal adenocarcinoma at 3 cm from the anal verge. The patient had Lynch syndrome, with a germline mutation in the PMS2 gene. A near-complete clinical response was observed after neoadjuvant chemoradiation (NCRT), and the patient wished to delay surgery and permanent colostomy. Additional FOLFOX was administered and led to a complete clinical response. After 2.5 months of watchful delay of surgery, the tumor regrew, and the patient then underwent robotic abdominoperineal resection (APR). Initial exploration revealed a highly redundant sigmoid colon. A pelvis-first approach was undertaken. The colon was left tethered and outside of the pelvis during the pelvic dissection. The levator ani was divided transabdominally. Vascular dissection and left colon mobilization were completed after pelvic dissection.2 The specimen was removed transanally, obviating the need for abdominal incision. An end colostomy was created laparoscopically, and the perineum was closed primarily after omental flap. The patient recovered without complications. The ‘pelvis-first’ approach to proctectomy is advantageous for patients with a highly redundant sigmoid colon. Transabdominal division of the levator ani during APR ensures excellent circumferential margin. Although Lynch syndrome-associated rectal cancer can show excellent response to NCRT,3 patients undergoing watchful delay of surgery require close monitoring and prompt triggering of salvage proctectomy when tumor regrowth is observed.4,5

Purpose 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. Methods 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. Results 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. Conclusion 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.

Because of the low incidence of nongastrointestinal stromal tumor (non-GIST) spindle cell sarcomas of the colon or rectum, the clinical behavior and ideal surgical treatment of these tumors and patient outcomes are poorly defined. The purpose of this study was to characterize these tumors and to determine the best surgical approach. We identified 1056 patients with non-GIST spindle cell sarcomas of the colon or rectum (1998-2010) in the National Cancer Database and collected data for each patient that included patient and tumor characteristics, tumor site (colon vs rectum), surgery type, and outcomes. The median overall survival was significantly longer in patients with rectal tumors than in those with colon tumors (P0.01). Patients with colon tumors who underwent anatomic surgical resection showed a trend toward longer median survival than those with no surgical treatment [hazard ratio (HR), 1.94; P = 0.09] or who underwent local excision (HR, 1.74; P = 0.09). Patients with rectal tumors did not benefit from anatomic surgical resection, but there was a trend favoring local excision (HR, 0.55; P = 0.06). Local sphincter-sparing procedures should be considered for rectal non-GIST tumors whenever technically feasible.

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 for 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-h/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.

Background: Improving the quality of health care is a national priority, and providing patient-centered care is one of the 6 key areas for quality improvement. In the setting of patients with young-onset colorectal cancer (CRC), appropriate genetic workup and testing for potential underlying inherited CRC syndromes is fundamental to patient-centered care. Lynch syndrome (LS) is the most common of these inherited syndromes, and current recommendations from the NCCN and other professional societies advocate universal screening for LS among young patients with CRC. However, practical implementation of these guidelines often falls short. Methods: We conducted a prospective quality improvement intervention trial to optimize universal screening for LS in young (age

Colon cancer surveillance guidelines do not routinely include positron emission tomography (PET) imaging; however, its use after surgical resection has been increasing. We evaluated the secular patterns of PET use after surgical resection of colon cancer among elderly patients and identified factors associated with its increasing use.We used the SEER-linked Medicare database (July 2001 through December 2009) to establish a retrospective cohort of patients age ≥ 66 years who had undergone surgical resection for colon cancer. Postoperative PET use was assessed with the test for trends. Patient, tumor, and treatment characteristics were analyzed using univariable and multivariable logistic regression analyses.Of the 39,221 patients with colon cancer, 6,326 (16.1%) had undergone a PET scan within 2 years after surgery. The use rate steadily increased over time. The majority of PET scans had been performed within 2 months after surgery. Among patients who had undergone a PET scan, 3,644 (57.6%) had also undergone preoperative imaging, and 1,977 (54.3%) of these patients had undergone reimaging with PET within 2 months after surgery. Marriage, year of diagnosis, tumor stage, preoperative imaging, postoperative visit to a medical oncologist, and adjuvant chemotherapy were significantly associated with increased PET use.PET use after colon cancer resection is steadily increasing, and further study is needed to understand the clinical value and effectiveness of PET scans and the reasons for this departure from guideline-concordant care.

BACKGROUND: Ileostomies are a routine part of the care of rectal cancer patients, but are associated with significant risk for dehydration, readmission, and acute kidney injury. Telemedicine has proven beneficial in decreasing readmission in chronic medical illnesses, but its utility in ileostomy patients is not well studied. OBJECTIVE: The purpose of this study was to evaluate the feasibility of televideoconferencing in the assessment of ileostomy output. DESIGN: An institutional review board-approved, prospective clinical trial was conducted at a single institution from November, 2014-December, 2015. SETTINGS: The study was conducted in a single, large academic medical center. PATIENTS: Patients >18 years of age undergoing surgery with plans for ileostomy were eligible. INTERVENTIONS: Televideoconference assessments of ileostomy output and the need for medical intervention were conducted during the postoperative stay and compared to in-person assessment. MAIN OUTCOME MEASURES: The primary endpoint of the trial was feasibility of using teleconferencing to assess the need for medical intervention, defined as 90% agreement between telemedicine and in-person assessments. Secondary endpoints included patient/provider satisfaction and correlative studies examined dehydration events and readmission. RESULTS: Twenty-seven patients underwent 44 teleconferencing assessments of ileostomy output. Compared to in-person treatment decisions, there was a 95% match (95% CI: 85%, 99%). The readmission rate for the study participants was 31% and 18% experienced dehydration events. Both patients and faculty responded favorably to surveys regarding the use of telemedicine in the perioperative period. LIMITATIONS: The study is limited by its in-hospital use of technology and small sample size. CONCLUSIONS: Televideoconference evaluation is a feasible, reliable means of assessing ileostomy output with high patient and physician acceptance. Our pilot study provides rationale for further study in the post-discharge setting for patients with ileostomies. The incorporation of televideoconference assessment within a teledischarge program may enable early intervention to improve patient outcomes.

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.