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Background: Patients with Crohn's disease face an elevated risk of colorectal cancer, in part due to underlying chronic inflammation. Biologic therapy is the mainstay of medical treatment; however, the impact of treatment on colorectal cancer-related outcomes remains unclear., Objective: To investigate the association between prior exposure to biologic treatment and colorectal cancer-related outcomes in patients with underlying Crohn's disease., Design: Retrospective cohort study., Settings: High volume, tertiary colorectal surgery department., Patients: Adults (older than 18 years) diagnosed with Crohn's disease and colorectal cancer who underwent curative operation between 1998 and 2020., Interventions: Exposure to any biologic IBD medication before cancer diagnosis., Main Outcome Measures: Survival and recurrence outcomes., Results: A total of 56 patients were included with a median age of 52.5 years (interquartile range, 18.9 years) at the time of surgery; 19 patients (33.9%) were treated with biologics before surgery; 10 (52.6%) received infliximab, 2 (10.5%) received adalimumab, and 7 (36.8%) received multiple biologics. Rectal cancer (57% vs 43.2%, p = 0.02) and well-differentiated or moderately differentiated tumors (93% vs 50%, p = 0.005) were more common in the biologic exposure group. Exposure to biologics was associated with a higher 5-year disease-free survival rate (80% vs 45%, p = 0.048), whereas the 5-year overall survival (93% vs 57%, p = 0.19) and 5-year recurrence rates (7% vs 31%, p = 0.18) were numerically but not statistically significant., Limitations: Retrospective, single-center study., Conclusions: In patients with Crohn's disease and colorectal adenocarcinoma who underwent curative surgery, those previously exposed to biologic therapy were more likely to have well-differentiated or moderately differentiated tumors, which were more likely to be distal to the splenic flexure. Biologic exposure was associated with significantly higher 5-year disease-free survival. These findings suggest that treatment of inflammation in patients with Crohn's disease fundamentally alters carcinogenesis pathways. See Video Abstract., La Terapia Biolgica Se Asocia Con Mejores Resultados Oncolgicos En El Cncer Colorrectal Asociado a La Enfermedad De Crohn: ANTECEDENTES:Los pacientes con enfermedad de Crohn enfrentan un riesgo elevado de cáncer colorrectal, en parte debido a la inflamación crónica subyacente. La terapia biológica es el pilar del tratamiento médico; sin embargo, el impacto del tratamiento en los resultados relacionados con el cáncer colorrectal sigue sin estar claro.OBJETIVO:Investigar la asociación entre la exposición previa al tratamiento biológico y los resultados relacionados con el cáncer colorrectal en pacientes con enfermedad de Crohn subyacente.DISEÑO:Estudio de cohorte retrospectivo.ESCENARIO:Departamento de cirugía colorrectal de alto volumen de tercer nivelPACIENTES:Adultos (>18 años) diagnosticados con enfermedad de Crohn y cáncer colorrectal que se sometieron a una operación curativa entre 1998 y 2020.INTERVENCIÓN(ES):Exposición a cualquier medicamento biológico para la EII antes del diagnóstico de cáncer.PRINCIPALES MEDIDAS DE RESULTADOS:Resultados de supervivencia y recurrenciaRESULTADOS:Se incluyeron 56 pacientes, con una mediana de edad de 52.5 años (RIC: 18.9 años) en el momento de la cirugía; 19 (33.9%) pacientes fueron tratados con agentes biológicos antes de la cirugía; 10 (52.6%) recibieron infliximab, 2 (10.5%) recibieron adalimumab y 7 (36.8%) habían recibido múltiples agentes biológicos. El cáncer rectal (57% frente a 43.2%, p = 0.02) y los tumores bien o moderadamente diferenciados (93% frente a 50%, p = 0.005) fueron más comunes en el grupo de exposición a agentes biológicos. La exposición a agentes biológicos se asoció con una mayor tasa de supervivencia libre de enfermedad a 5 años (80% frente a 45%, p = 0.048), mientras que la supervivencia general a 5 años (93% frente a 57%, p = 0.19) y las tasas de recurrencia a 5 años (7% frente a 31%, p = 0.18) fueron numéricamente, pero no estadísticamente significativas.LIMITACIONES:Estudio retrospectivo de un solo centro.CONCLUSIONES:En pacientes con enfermedad de Crohn y adenocarcinoma colorrectal que se sometieron a cirugía curativa, aquellos expuestos previamente a terapia biológica tuvieron más probabilidades de tener tumores bien/moderadamente diferenciados, y tenían más probabilidades de estar distales al ángulo esplénico, asociados con una supervivencia libre de enfermedad a 5 años significativamente mayor. Estos hallazgos sugieren que el tratamiento de la inflamación en pacientes con enfermedad de Crohn altera fundamentalmente las vías de la carcinogénesis. (Traducción-Dr. Jorge Silva Velazco)., (Copyright © The ASCRS 2024.)

Background: Endoscopic submucosal dissection is increasingly used to treat early-stage colorectal cancer. This study evaluated the feasibility of endoscopic submucosal dissection in this setting and the determinants of lymph node metastasis., Methods: We reviewed patients who underwent colorectal endoscopic submucosal dissection for early-stage colorectal cancer at a tertiary center between 2011 and 2023. The primary outcome was the identification of high-risk pathologic features predictive of lymph node metastasis in patients undergoing oncologic colon resection following endoscopic submucosal dissection., Results: We reviewed 1,398 patients who underwent endoscopic submucosal dissection, and 83 (6%) had colorectal cancer. Twenty-four patients (29%) were closely monitored after endoscopic submucosal dissection, and 59 (71%) underwent oncologic colon resection because of high-risk pathologies of the endoscopic submucosal dissection specimen. In the oncologic colon resection group, the mean age was 62.7 years (±10.2), with 56% male predominance, and 14% showed positive lymph nodes in the final pathology. Analysis comparing patients with and without lymph node metastasis showed significant differences in sex, lesion size, submucosal invasion depth, and budding scores. Multivariate analysis showed that lesions with a submucosal invasion depth ≥2.00 mm of the endoscopic submucosal dissection resection specimen had higher odds of lymph node metastasis (odds ratio 18.7, P = .028), whereas lesions with a diameter >20 mm were associated with a lower likelihood of lymph node metastasis (odds ratio 0.07, P = .036)., Conclusion: The study highlights the oncologic safety of early-stage endoscopic submucosal dissection as a viable treatment option for carefully selected patients with colorectal cancer. After tissue resection with endoscopic submucosal dissection, if the lesion size is less than 20 mm, depth of invasion up to 2 mm may be considered safe in the absence of other high-risk pathologic factors., (Published by Elsevier Inc.)

The incidence of colorectal cancer (CRC) among individuals younger than age 50 (early-onset CRC [EOCRC]) has substantially increased, and yet the etiology and molecular mechanisms underlying this alarming rise remain unclear. We compared tumor-associated T-cell repertoires between EOCRC and average-onset CRC (AOCRC) to uncover potentially unique immune microenvironment-related features by age of onset. Our discovery cohort included 242 patients who underwent surgical resection at Cleveland Clinic from 2000 to 2020. EOCRC was defined as younger than age 50 years at diagnosis (N = 126) and AOCRC as 60 years of age or older (N = 116). T-cell receptor (TCR) abundance and clonality were measured by immunosequencing of tumors. Logistic regression models were used to evaluate the associations between TCR repertoire features and age of onset, adjusting for sex, race, tumor location, and stage. Findings were replicated in 152 EOCRC and 1984 AOCRC cases from the Molecular Epidemiology of Colorectal Cancer Study. EOCRC tumors had significantly higher TCR diversity compared with AOCRC tumors in the discovery cohort (odds ratio [OR] = 0.44, 95% confidence interval [CI] = 0.32 to 0.61, P < .0001). This association was also observed in the replication cohort (OR = 0.74, 95% CI = 0.62 to 0.89, P = .0013). No significant differences in TCR abundance were observed between EOCRC and AOCRC in either cohort. Higher TCR diversity, suggesting a more diverse intratumoral T-cell response, is more frequently observed in EOCRC than AOCRC. Further studies are warranted to investigate the role of T-cell diversity and the adaptive immune response more broadly in the etiology and outcomes of EOCRC., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Colorectal cancer (CRC) is rising in young adults between ages 20 to 49 years. CRC screening is endorsed for average-risk individuals beginning at ages 45 to 49 years. Targeting screening for individuals <45 years may be warranted if risk factors for advanced neoplasia can be identified., Aim: To identify factors associated with advanced colorectal neoplasia in adults aged <45 years., Method: Individuals ages 18 to 44 years who underwent colonoscopy at Cleveland Clinic between 2011 and 2021 with ≥1 advanced neoplasm (AN) were included. Patients with inflammatory bowel disease or inherited CRC syndromes were excluded. Demographics, comorbidities, family history of CRC, and colonoscopy indication were obtained. Patients with a normal colonoscopy constituted the control group. A multivariable logistic regression model was used to investigate the relationship between clinical variables and the presence of advanced colorectal neoplasia., Results: In all, 13,006 patients were included, of which 651 (5%) patients had AN: 404 (62%) with tubular adenoma ≥10 mm, 29 (4.5%) tubular adenoma with high-grade dysplasia, 210 (32%) tubulovillous adenomas, 27 (4%) traditional serrated adenomas, 82 (13%) sessile serrated lesions ≥10 mm, 7(2%) sessile serrated lesions with dysplasia, and 29 (4.4%) patients had a CRC. Factors associated with AN were older age (means 38.5 vs. 36.6 y), history of smoking, diabetes, non-White race, higher body mass index (29.9 vs. 28.5 kg/m 2 ), and lower vitamin D (27.6 vs. 32.2 ng/dl), all P <0.001. In the reduced multivariable model, factors associated with AN included tobacco use (OR 2.026 (current vs. never, P <0.0001), age (OR increase by 1.06 per year, P <0.0001), male gender (OR 1.476, P <0.0001), family history of CRC (OR 3.91, P <0.0001), aspirin use (1.31, P =0.035), and diabetes (OR 2.106, P 0.001)., Conclusion: Increasing age, male gender, exposure to tobacco, family history of CRC, diabetes, and aspirin use were independently associated with advanced neoplasia in adults younger than 45. Targeted early screening to young adults with these risk factors may be justified. Large collaborative prospective studies are needed to validate our findings., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Advanced endoscopic resection techniques are used to treat colorectal neoplasms that are not amenable to conventional colonoscopic resection. Literature regarding the predictors of the outcomes of advanced endoscopic resections, especially from a colorectal surgical unit, is limited., Objective: To determine the predictors of short-term and long-term outcomes after advanced endoscopic resections., Design: Retrospective case series., Settings: Tertiary care center., Patients: Patients who underwent advanced endoscopic resections for colorectal neoplasms from November 2011 to August 2022., Interventions: Endoscopic mucosal resection, endoscopic submucosal dissection, hybrid endoscopic submucosal dissection, and combined endoscopic laparoscopic surgery., Main Outcome Measures: Predictors of en bloc and R0 resection, bleeding, and perforation were determined using univariable and multivariable logistic regression models. Cox regression models were used to determine the predictors of tumor recurrence., Results: A total of 1213 colorectal lesions from 1047 patients were resected (median age 66 [interquartile range, 58-72] years, 484 women [46.2%], median BMI 28.6 [interquartile range, 24.8-32.6]). Most neoplasms were in the proximal colon (898; 74%). The median lesion size was 30 (interquartile range, 20-40; range, 0-120) mm. Nine hundred eleven lesions (75.1%) underwent previous interventions. The most common Paris and Kudo classifications were 0 to IIa flat elevation (444; 36.6%) and IIIs (301; 24.8%), respectively. En bloc and R0 resection rates were 56.6% and 54.3%, respectively. Smaller lesions, rectal location, and procedure type (endoscopic submucosal dissection) were associated with significantly higher en bloc and R0 resection rates. Bleeding and perforation rates were 5% and 6.6%, respectively. Increased age was a predictor for bleeding (OR 1.06; 95% CI, 1.03-1.09; p < 0.0001). Lesion size was a predictor for perforation (OR 1.02; 95% CI, 1.00-1.03; p = 0.03). The tumor recurrence rate was 6.6%. En bloc (HR 1.41; 95% CI, 1.05-1.93; p = 0.02) and R0 resection (HR 1.49; 95% CI, 1.11-2.06; p = 0.008) were associated with decreased recurrence risk., Limitations: Single-center, retrospective study., Conclusions: Outcomes of advanced endoscopic resections can be predicted by patient-related and lesion-related characteristics. See Video Abstract ., Predictores De La Reseccion R, En Bloque Y Las Complicaciones Por Resecciones Endoscpicas Avanzadas En Casos De Neoplasia Colorrectal Resultados De Procedimientos: ANTECEDENTES:Las técnicas avanzadas de resección endoscópica se utilizan para el tratamiento de neoplasias colorrectales que no son susceptibles de resección colonoscópica convencional. La literatura sobre los predictores de los resultados de las resecciones endoscópicas avanzadas, especialmente en una unidad de cirugía colorrectal, es limitada.OBJETIVO:Determinar los predictores de resultados a corto y largo plazo después de resecciones endoscópicas avanzadas.DISEÑO:Serie de casos retrospectivos.LUGAR:Centro de tercer nivel de atención.PACIENTES:Pacientes sometidos a resecciones endoscópicas avanzadas por neoplasias colorrectales desde noviembre de 2011 hasta agosto de 2022.INTERVENCIÓNES:Resección endoscópica de la mucosa, disección endoscópica submucosa (ESD), ESD híbrida, cirugía laparoscópica endoscópica combinada.PRINCIPALES MEDIDAS DE RESULTADO:Los predictores de resección en bloque y R0, sangrado y perforación se determinaron mediante modelos de regresión logística univariables y multivariables. Se utilizaron modelos de regresión de Cox para determinar los predictores de recurrencia del tumor.RESULTADOS:Se resecaron 1.213 lesiones colorrectales en 1.047 pacientes [edad media 66 (58-72) años, 484 (46,2%) mujeres, índice de masa corporal medio 28,6 (24,8-32,6) kg/m 2 ]. La mayoría de las neoplasias se encontraban en el colon proximal (898, 74%). El tamaño medio de la lesión fue de 30mm (RIC: 20-40, rango: 0-120). 911 (75,1%) lesiones tenían intervenciones previas. Las clasificaciones de París y Kudo más comunes fueron 0-IIa elevación plana (444, 36,6%) y III (301, 24,8%), respectivamente. Las tasas de resección en bloque y R0 fueron del 56,6% y 54,3%, respectivamente. Las lesiones más pequeñas, la ubicación rectal y el tipo de procedimiento (ESD) se asociaron con tasas de resección en bloque y R0 significativamente más altas. Las tasas de sangrado y perforación fueron del 5% y 6,6%, respectivamente. La edad avanzada [1,06 (1,03-1,09), p < 0,0001] fue un predictor de sangrado. El tamaño de la lesión [1,02 (1,00-1,03), p = 0,03] fue un predictor de perforación. La tasa de recurrencia del tumor fue del 6,6%. En bloque [HR 1,41 (IC 95% 1,05-1,93), p = 0,02] y la resección R0 [HR 1,49 (IC 95% 1,11-2,06), p = 0,008] se asociaron con un menor riesgo de recurrencia.LIMITACIONES:Estudio unicéntrico, retrospectivo.CONCLUSIONES:Los resultados de las resecciones endoscópicas avanzadas pueden predecirse según las características del paciente y de la lesión. (Traducción-Dr. Xavier Delgadillo )., (Copyright © The ASCRS 2024.)

Aim: Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the treatment of choice for colorectal cancer (CRC) in inflammatory bowel disease. CRC may also be discovered incidentally at IPAA for other indications. We sought to determine whether incidentally found CRC at IPAA was associated with worse outcomes., Methods: Our institutional pouch registry (1983-2021) was retrospectively reviewed. Patients with CRC at pathology after IPAA were divided into two groups: a preoperative diagnosis (PreD) group and an incidental diagnosis (InD) group. Their long-term outcomes (overall survival, disease-free survival and pouch survival) were compared., Results: We included 164 patients: 53 (32%) InD and 111 (68%) PreD. There were no differences in cancer staging, differentiation and location. After a median follow-up of 11 (IQR 3-25) years for InD and 9 (IQR 3-20) years for the PreD group, deaths were 14 (26%) in the InD group and 18 (16%) in the PreD group. Pouch failures were five (9%) in the InD group and nine (8%) in the PreD group, of which two (5%) and four (4%) were cancer related. Ten-year overall survival was 94% for InD and 89% for PreD (P = 0.41), disease-free survival was 95% for InD and 90% for PreD (P = 0.685) and pouch survival was 89% for InD and 97% for PreD (P = 0.80). Pouch survival at 10 years was lower in rectal versus colon cancer (87% vs. 97%, P = 0.01). No difference was found in outcomes in handsewn versus stapled anastomoses., Conclusion: Inflammatory bowel disease patients with incidentally found CRC during IPAA appear to have similarly excellent oncological and pouch outcomes to patients with a preoperative cancer diagnosis., (© 2024 Association of Coloproctology of Great Britain and Ireland.)

Deleterious effects of environmental exposures may contribute to the rising incidence of early-onset colorectal cancer (eoCRC). We assessed the metabolomic differences between patients with eoCRC, average-onset CRC (aoCRC), and non-CRC controls, to understand pathogenic mechanisms. Patients with stage I-IV CRC and non-CRC controls were categorized based on age ≤ 50 years (eoCRC or young non-CRC controls) or  ≥ 60 years (aoCRC or older non-CRC controls). Differential metabolite abundance and metabolic pathway analyses were performed on plasma samples. Multivariate Cox proportional hazards modeling was used for survival analyses. All P values were adjusted for multiple testing (false discovery rate, FDR P < 0.15 considered significant). The study population comprised 170 patients with CRC (66 eoCRC and 104 aoCRC) and 49 non-CRC controls (34 young and 15 older). Citrate was differentially abundant in aoCRC vs. eoCRC in adjusted analysis (Odds Ratio = 21.8, FDR P = 0.04). Metabolic pathways altered in patients with aoCRC versus eoCRC included arginine biosynthesis, FDR P = 0.02; glyoxylate and dicarboxylate metabolism, FDR P = 0.005; citrate cycle, FDR P = 0.04; alanine, aspartate, and glutamate metabolism, FDR P = 0.01; glycine, serine, and threonine metabolism, FDR P = 0.14; and amino-acid t-RNA biosynthesis, FDR P = 0.01. 4-hydroxyhippuric acid was significantly associated with overall survival in all patients with CRC (Hazards ratio, HR = 0.4, 95% CI 0.3-0.7, FDR P = 0.05). We identified several unique metabolic alterations, particularly the significant differential abundance of citrate in aoCRC versus eoCRC. Arginine biosynthesis was the most enriched by the differentially altered metabolites. The findings hold promise in developing strategies for early detection and novel therapies., (© 2024. The Author(s).)

Background: The unexplained rise of young-onset CRC (yoCRC, age <50 years) is of concern. Evidence suggests that microbial dysbiosis may be a contributing factor, but the tumor microbial profile of yoCRC in comparison to average-onset CRC (aoCRC, age >60) has not been fully investigated., Methods: 16S rRNA amplicon sequencing was performed in tumor and paired adjacent non-malignant fresh frozen tissue specimens prospectively collected from 136 yoCRC and 140 aoCRC patients. Phyloseq, microbiomeSeq, metagenomeSeq, and NetComi were utilized for bioinformatics analysis. Statistical tests included Fisher's exact test, ANOVA, PERMANOVA with Bonferroni correction, linear regression, and Wilcoxon test. p-value <0.05 was considered statistically significant., Findings: yoCRC patients were more likely to have left-sided (72.8 vs. 54.3%), rectal (36.7% vs. 25%), and stage IV (28% vs. 15%) tumors. yoCRC tumors had significantly higher microbial alpha diversity (p = 1.5 × 10 -5 ) and varied beta diversity (R2 = 0.31, p = 0.013) than aoCRC tumors. yoCRC tumors were enriched with Akkermansia and Bacteroides, whereas aoCRC tumors showed greater relative abundances of Bacillus, Staphylococcus, Listeria, Enterococcus, Pseudomonas, Fusobacterium, and Escherichia/Shigella. Akkermansia had a predominantly negative correlation with the microbial communities in yoCRC tumors. yoCRC and aoCRC tumors had distinct microbial profiles associated with tumor location, sidedness, stage, and obesity. Fusobacterium (R2 = -0.23, p = 0.001) and Akkermansia (R2 = 0.05, p = 0.001) abundance correlated with overall survival in yoCRC., Interpretation: Our study provides a comprehensive understanding of the microbial perturbations in yoCRC tumors. We identify microbial candidates that may highlight a distinct pathogenesis of yoCRC and serve as preventive, diagnostic, and therapeutic targets., Funding: Sondra and Stephen Hardis Chair in Oncology Research (A.A.K.)., Competing Interests: Declaration of interests S.V.B., N.S., K.G.N., S.L.S., and S.X. report no conflicts of interest. S.K. reports consulting and advisory roles in Exelixis, Tempus, Guardant Health, and SeaGen. D.L. reports consulting and advisory roles in Olympus Medical Systems and research funding from Merck. A.A.K. reports consulting honoraria from Janssen, Bayer, BMS, Sanofi, Pfizer, and Anthos., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Aim: Due to their rarity, the management of colorectal gastrointestinal stromal tumours (CR GISTs) is still under debate. The aim of this study was to assess prognostic factors., Method: We performed a retrospective review of patients who underwent surgery with curative intent for CR GIST at our centre from 2002 to 2019. Factors associated with overall (OS) and recurrence-free survival (RFS) were analysed., Results: Fifty-six patients were included [median age 63 years, 29 (52%) female, 30 (54%) Miettinen high-risk, 40 (71%) with rectal GIST]. Nineteen (34%) patients received perioperative (neoadjuvant and/or adjuvant) imatinib. All cases of colonic GIST had an R0 resection, compared with 28 (70%) of rectal GISTs. After a median follow-up of 97 months (interquartile range 48-155 months), 14 (25%) deaths and 14 (25%) recurrences occurred. In the high-risk cohort, factors associated with improved RFS were R0 resection (OR 0.19, 95% CI 0.1-0.5, p = 0.002) and perioperative imatinib (OR 0.33, 95% CI 0.42-0.97, p = 0.04). Patients who had received perioperative imatinib had longer RFS (60% vs. 11% at 5 years, p = 0.006) but not OS. In rectal GISTs, 5-year OS was 85% for R0 and 70% for R1 resections (p = 0.164) and 5-year RFS was 85% for R0 and 12% for R1 resection (p < 0.001). When stratifying patients by perioperative imatinib, there were no differences in OS or RFS in the R0 or R1 groups., Conclusion: Perioperative imatinib and R0 resection were associated with improved RFS in high-risk patients with CR GIST. In patients with rectal GIST, R1 resection was associated with worse RFS irrespective of perioperative imatinib treatment., (© 2023 Association of Coloproctology of Great Britain and Ireland.)

Background: The incidence of early-onset colorectal cancer (EOCRC) is rapidly increasing. Pathogenic germline variants (PGVs) are detected in 16% to 20% of patients who have EOCRC, highlighting a need for genetic counseling (GC) and multigene panel testing in these patients. We aimed to determine the rate of referral to GC and uptake and outcomes of germline testing in patients with EOCRC., Methods: We conducted a retrospective cohort study of patients aged <50 years diagnosed with colorectal cancer (CRC) from 2010 to 2019 at Cleveland Clinic. Demographic data were extracted, including age, sex, self-reported race, and family history of CRC. The proportions of patients with GC referral and completion of GC and genetic testing were investigated, and genetic testing results were analyzed. Multivariable logistic regression analysis was conducted to identify factors independently associated with GC referral and uptake., Results: A total of 791 patients with EOCRC (57% male and 43% female) were included; 62% were referred for GC, and of those who were referred, 79% completed a GC appointment and 77% underwent genetic testing. Of those who underwent testing, 21% had a PGV detected; 82% were in known CRC-associated genes, with those associated with Lynch syndrome and familial adenomatous polyposis the most common, and 11% were in other actionable genes. Referral to GC was positively associated with family history of CRC (odds ratio [OR], 2.11; 95% CI, 1.51-2.96) and more recent year of diagnosis (2010-2013 vs 2017-2019; OR, 5.36; 95% CI, 3.59-8.01) but negatively associated with older age at diagnosis (OR, 0.89; 95% CI, 0.86-0.92)., Conclusions: Referral to GC for patients with EOCRC is increasing over time; however, even in recent years, almost 25% of patients were not referred for GC. We found that 1 in 5 patients with EOCRC carry actionable PGVs, highlighting the need for health systems to implement care pathways to optimize GC referral and testing in all patients with EOCRC.

Purpose: New guidelines recommend considering germline genetic testing for all patients with colorectal cancer (CRC). However, there is a lack of data on stakeholders' perspectives on the advantages and barriers of implementing universal germline testing (UGT). This study assessed the perspectives of members of the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer (CGA-IGC) regarding the implementation of UGT for patients with CRC, including readiness, logistics, and barriers., Methods: A cross-sectional survey was sent to 317 active members of CGA-IGC. The survey included sections on demographics, clinical practice specialty, established institutional practices for testing, and questions pertaining to support of and barriers to implementing UGT for patients with CRC., Results: Eighty CGA-IGC members (25%) participated, including 42 genetic counselors (53%) and 14 gastroenterologists (18%). Forty-seven (59%) reported an academic medical center as their primary work setting, and most participants (56%) had more than 10 years of clinical practice. Although most participants (73%) supported UGT, 54% indicated that changes in practice would be required before adopting UGT, and 39% indicated that these changes would be challenging to implement. There was support for both genetics and nongenetics providers to order genetic testing, and a majority (57%) supported a standardized multigene panel rather than a customized gene panel. Key barriers to UGT implementation included limited genetics knowledge among nongenetics providers, time-consuming processes for obtaining consent, ordering tests, disclosing results, and lack of insurance coverage., Conclusion: This study demonstrates wide support among hereditary GI cancer experts for implementation of UGT for patients with CRC. However, alternative service delivery models using nongenetics providers should be considered to address the logistical barriers to UGT implementation, particularly the growing demand for genetic testing.

Background and Aims: Lynch syndrome (LS) is the most common hereditary cause of colorectal cancer (CRC) and endometrial cancer (EC). Although colonoscopy reduces CRC in LS, the protection is variable. We assessed the prevalence and incidence of neoplasia in LS during surveillance colonoscopy in the United States and factors associated with advanced neoplasia., Methods: Patients with LS undergoing ≥1 surveillance colonoscopy and with no personal history of invasive CRC or colorectal surgery were included. Prevalent and incident neoplasia was defined as occurring <6 months before and ≥6 months after germline diagnosis of LS, respectively. We assessed advanced adenoma (AA), CRC, and the impact of mismatch repair pathogenic variant (PV) and typical LS cancer history (personal history of EC and/or family history of EC/CRC) on outcome., Results: A total of 132 patients (inclusive of 112 undergoing prevalent and incident surveillance) were included. The median examination interval and duration of prevalent and incident surveillance was .88 and 1.06 years and 3.1 and 4.6 years, respectively. Prevalent and incident AA were detected in 10.7% and 6.1% and invasive CRC in 0% and 2.3% of patients. All incident CRC occurred in MSH2 and MLH1 PV carriers and only 1 (.7%) while under surveillance in our center. AAs were detected in both LS cancer history cohorts and represented in all PVs., Conclusions: In a U.S. cohort of LS, advanced neoplasia rarely occurred over annual surveillance. CRC was diagnosed only in MSH2/MLH1 PV carriers. AAs occurred regardless of PV or LS cancer history. Prospective studies are warranted to confirm our findings., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Backgrounds: Milk of magnesia (MoM) has been reported to accelerate return of bowel function following surgery. However, there is insufficient evidence regarding the impact of MoM on postoperative recovery after colorectal surgery. We aimed to determine the impact of MoM on postoperative length of stay in patients undergoing colorectal surgery., Methods: All patients who underwent colorectal resection without an ileostomy between 2015 and 2018 were included. Patients were divided into two groups based on whether postoperative MoM (MoM) was administered or not, according to surgeons' prescribing preferences. Consecutive patients of surgeons who prescribe MoM were included in the MoM group, while consecutive patients of surgeons who prefer not to prescribe MoM served as the control group. Age, gender, preoperative comorbidities, surgical approach, length of stay, readmission, postoperative complications and mortality were evaluated and compared between the groups., Results: A total of 3292 patients were included; 523 (15.9%) patients were prescribed MoM. Patients in the MoM group were found to be significantly older, with higher BMI and ASA class, and more often undergoing operations for cancer resection or colostomy creations, than the control group. Postoperative complications were comparable between the groups. On multivariable linear regression, MoM use was associated with a 14.1% reduction in length of stay (MoM group 4 (2; 8), control group 5 (3; 8 P = 0.006))., Conclusion: MoM as adjunct medication in the postoperative period following colorectal surgery is associated with reduced length of stay, without an increase in postoperative complications., (© 2022 The Authors. ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Background: The aims of this study were to determine the impact of race and socioeconomics on survival in patients with stage IV colorectal cancer., Methods: A prospective database of stage IV colorectal cancer patients treated at a multi-hospital health system from 2015 to 2019 was retrospectively analyzed. Univariate and multivariate survival analysis using log-rank Mantel-Cox test and Cox proportional hazard model were performed to determine the impact of race, socioeconomic factors, presentation, and treatment on overall survival., Results: 4012 patients were diagnosed with colorectal cancer, of which 803 patients were stage IV. There were 677 (84.3%) White, and 108 (13.4%) Black patients. Black patients have worse 5-year overall survival than white patients (HR 1.43 (1.09-1.87)). Patients who received chemotherapy had significantly better survival than patients who did not receive chemotherapy (HR 0.58 (0.47-0.71)). Black patients have significantly lower rates of receiving chemotherapy as compared to white patients (61.1% vs 75.37%, p = 0.0018)., Conclusion: Patients with Stage IV colorectal cancer have worse survival if they are black, older age, and did not receive chemotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The surface morphology of colorectal polyps is well correlated with submucosal invasion in Eastern Countries but not in North America. We aimed to investigate associations between the Paris classification, surface morphology, and Kudo pit pattern to submucosal invasion in advanced endoscopic resection techniques., Methods: We retrospectively analyzed prospectively collected data of consecutive advanced endoscopic procedures conducted by a single surgeon between August 2017 and October 2018. The data included patients' demographics, the endoscopic finding of polyps (Paris, Kudo, and surface morphology), and pathology results., Results: The study consisted of 138 lesions, and the mean age was 67 ± 10 years. The most common polyp locations were cecum (n = 41, 30%) followed by ascending colon (n = 28, 20%), and sigmoid colon (n = 18, 13%).The median polyp size was 30 mm (25-40). The en-bloc resection rate was 96%, and 11 (8%) polyps had adenocarcinoma with submucosal invasion. Nine patients (6.5%) had late bleeding, and 3 (2.2%) perforation occurred. Polyps with pit pattern of Kudo IV (n = 4, 36.4%) and Kudo V (n = 6, 54.5%) were associated with submucosal invasion., Conclusions: Surface morphology and pit pattern can predict submucosal invasion in the North American patient population. Polyp morphology may aid polyp selection for advanced endoscopic interventions., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background & Aims: Patients with early-onset colorectal cancer (eoCRC) are managed according to guidelines that are not age-specific. A multidisciplinary international group (DIRECt), composed of 69 experts, was convened to develop the first evidence-based consensus recommendations for eoCRC., Methods: After reviewing the published literature, a Delphi methodology was used to draft and respond to clinically relevant questions. Each statement underwent 3 rounds of voting and reached a consensus level of agreement of ≥80%., Results: The DIRECt group produced 31 statements in 7 areas of interest: diagnosis, risk factors, genetics, pathology-oncology, endoscopy, therapy, and supportive care. There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery. On the basis of current evidence, endoscopic, surgical, and oncologic treatment of eoCRC should not differ from later-onset CRC, except for individuals with pathogenic or likely pathogenic germline variants. The evidence on chemotherapy is not sufficient to recommend changes to established therapeutic protocols. Fertility preservation and sexual health are important to address in eoCRC survivors. The DIRECt group highlighted areas with knowledge gaps that should be prioritized in future research efforts, including age at first screening for the general population, use of fecal immunochemical tests, chemotherapy, endoscopic therapy, and post-treatment surveillance for eoCRC patients., Conclusions: The DIRECt group produced the first consensus recommendations on eoCRC. All statements should be considered together with the accompanying comments and literature reviews. We highlighted areas where research should be prioritized. These guidelines represent a useful tool for clinicians caring for patients with eoCRC., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Although endoscopic submucosal dissection provides higher en-bloc resection rates for larger colorectal lesions, it has not been widely adopted because of technical difficulties. Here we present our initial experience with a novel device facilitating endoluminal surgery., Impact of Innovation: The impact of innovation is the development of an endoluminal device increasing the utilization of the endoscopic submucosal dissection technique with higher success rates and lower complications., Technology Materials and Methods: This was a single-center experimental feasibility study involving 15 patients who had undergone endoscopic submucosal dissection between August 2019 and December 2020. The DiLumen C2 device was used selectively in patients with complex colorectal lesions., Preliminary Results: Fifteen patients with complex colorectal lesions underwent endoscopic submucosal dissection with a mean age of 64.5 years. The mean lesion size was 40.7 mm. All patients except 1 had an R0 en-bloc endoscopic submucosal dissection resection. There were no procedural or postprocedural complications. The median length of stay was 1 day., Conclusion: We report the safety and feasibility of the novel endoscopic platform facilitating en-bloc resection of colorectal lesions., Future Directions: The study needs validation in larger comparative series of patients with longer follow-up., (Copyright © The ASCRS 2022.)

Background: We aimed to compare the outcomes and the cost differences of endoscopic submucosal dissection (ESD) procedures in the endoscopy suite (ES) versus the operating room (OR)., Materials and Methods: The procedures in the OR were compared with procedures performed in the ES for demographics, lesion characteristics, procedure outcome, and procedure charges. The study included 163 procedures in the ES and 73 in the OR., Results: Both were similar in age, sex, body mass index, and intraprocedural and postoperative 30-day (late) complications. ES cases had significantly greater polyp size, were more commonly right-sided polyps, and had shorter hospital stays, with similar en bloc and margin-negative resection rates. The overall cost ratio of ESD procedures in ES to OR was 0.47 ( P <0.001)., Conclusions: Colorectal ESD procedures performed in the ES have similar efficacy and safety as those in the OR. Procedures performed in the ES were associated with a shorter length of stay and significant periprocedural cost savings., Competing Interests: A.M. is a consultant for Olympus, Boston Scientific, Medtronics, DiLumen. Royalties from Medtronic. D.L. is a consultant for Olympus. E.G. is a consultant for DiLumen, Olympus, and Boston Scientific. The remaining authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: An obscured vision of surgical field during laparoscopic surgery is inconvenient. Several temporary methods were described as solutions to loss of vision, and common practice is scope removal, cleaning, and heating. A lately developed and introduced device claims continuous clear vision during laparoscopic surgery. This study aims to present our initial experience with the device during laparoscopic colorectal surgery., Materials and Methods: We have included medical records of all patients scheduled for laparoscopic colorectal surgery with the device between March and August 2021 at Cleveland Clinic. Patient demographics, surgery type and time, the number of loss of vision events were recorded., Results: Fifteen patients underwent laparoscopic colorectal surgery during the study period. The median age was 42 (range: 25 to 86) years, and 10 (66%) were female. The median surgery time was 127 (range: 67 to 240) minutes, and the median loss of vision event number was 3 (1 to 6) per surgery. There was no need for laparoscope removal during any of the surgeries. All surgeries were completed without any intraoperative complications., Conclusion: The novel system, provides clear vision during laparoscopic colorectal surgery with no need of scope removal for loss of vision events. The system provides removal of particulate gathering on the tip of the scope., Competing Interests: D.L. is consultant for Olympus. E.G. is consultant for Olympus, DiLumen, and Boston Scientific and receives honorarium from OpClear. The remaining authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: There exists conflicting data in the literature with regard to adequate adenoma detection rate (ADR) as well as other quality metrics during colonoscopy based on the time of day that the procedure is performed. The aim of this study was to investigate the effect of time of day on quality metrics in patients undergoing screening colonoscopy., Methods: Screening colonoscopies performed between January 2010 and September 2018 by twenty-eight colorectal surgeons were queried from a prospectively maintained database. Quality parameters examined included adenoma detection rate (ADR), gender-specific ADR, withdrawal time, total examination time, cecal intubation rate, bowel preparation quality, and intra-procedural complications. Colonoscopies were compared between morning (07:30-11:59 AM) and afternoon (12:00-17:00 PM) groups., Results: There were 13,809 endoscopic screening examinations performed in asymptomatic patients older than 45 years. Patients had a mean age of 59.8 years, and 48.5% were female. A total of 8868 (64%) of the scopes were performed in the morning and 4941 (36%) were performed in the afternoon. Median endoscopist volume was 189 [54, 701] and included only surgeons who performed both afternoon and morning colonoscopies. There was no difference in both ADR and bowel preparation quality between the two groups. Both groups exceeded all national quality benchmarks, with the morning group having significantly shorter examination times., Conclusions: In our practice, colonoscopies meet and exceed all national quality benchmarks, independent of the time of day they are performed., (Copyright © 2021. Published by Elsevier Inc.)

Background: Although the risk of colorectal cancer increases with advancing age, there remains a lack of guidelines for surveillance colonoscopy in the octogenarian and older population. Our objective is to document the diagnostic yield of surveillance colonoscopies, and to analyze adenoma characteristics, complications, and short-term survival in asymptomatic octogenarian and older patients undergoing adenoma surveillance colonoscopy., Methods: Surveillance colonoscopies performed at a tertiary level hospital colorectal surgery department between January 2010 and September 2018 were queried from a prospectively maintained institutional colonoscopy database. Patients 80 years old or older undergoing routine surveillance colonoscopy after having had an adenoma or advanced adenoma diagnosed on a prior exam were included in the study., Results: 604 patients were included in the study with a median age of 82 and 43% were female. Median follow-up was 52 months (range 2-110), with 511(85%) patients alive at their last available follow-up. Overall, 292 patients had at least one had adenomatous lesion and 105 (17.4%) patients had advanced adenomas. Increasing age was not associated with increased rate of sessile serrated lesions (p = 0.2) however, there was an association between increasing age and advanced adenoma rates (p = 0.01). Advanced adenomas were more commonly found to be right-sided (p = 0.02). Four asymptomatic patients were diagnosed with cancer at surveillance (0.6%)., Conclusions: Patients 80 years of age or older with a previous history of colorectal adenoma(s) may have a high risk of future advanced lesions and can be considered to undergo surveillance colonoscopy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Hereditary colorectal cancer (HCRC) syndromes account for 10% of colorectal cancers but remain underdiagnosed. This feasibility project tested the utility of an artificial intelligence-based chatbot deployed to patients scheduled for colonoscopy to identify HCRC risk factors, educate participants about HCRC and obtain consent to genetic testing as an extension of genetic counselling of appropriate subjects. Genetic counsellor (GC) and genetic counselling assistant (GCA) time spent per subject was also measured., Methods: Patients scheduled for colonoscopy at Cleveland Clinic were invited via electronic medical record patient portal or letter prior to colonoscopy with a link to a chatbot administering the Colon Cancer Risk Assessment Tool (CCRAT) to screen for HCRC syndromes. Those with ≥1 positive response to a CCRAT question received chatbot-deployed genetic education and the option to receive genetic testing. An order for a 55-gene pan-cancer panel was placed for those consenting, and the subject had blood drawn on the day of colonoscopy. Results were disclosed by a GC or GCA by telephone. Subject demographics, progression through the chat, responses to CCRAT, personal and family history, genetic test results and communication with the subject were recorded. Descriptive statistics and two-tailed unpaired t-test and Fisher's exact test were used., Results: 506/4254 (11.9%) initiated and 487 (96.2%) completed the chat with the chatbot. 215 (44.1%) answered 'yes' to ≥1 CCRAT question and all completed pretest education. 129/181 (71.3%) subjects who consented completed testing, and 12 (9.3%) were found to have a germline pathogenic variant. Per subject, the GC spent a mean of 14.3 (SD 7.3) and the GCA a mean of 19.2 (SD 9.8) minutes., Conclusion: The use of a chatbot in this setting was a novel and feasible method, with the potential of increasing genetic screening and testing in individuals at risk of HCRC syndromes., Competing Interests: Competing interests: BH is on the advisory board for Invitae; CE is (pro bono) chief medical officer of Family Care Path, Inc, and of Covariance LLC/PlexSeq Diagnostics., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The incidence of colorectal cancer (CRC) in patients under age 50 is rising for unclear reasons. We examined the effects of socioeconomic factors on outcomes for patients with early-onset CRC compared to late-onset CRC., Methods: Patients with CRC from 2004 to 2015 in the National Cancer Database were included and categorized by age (under or over 50 years). Differences in demographic and socioeconomic factors, disease characteristics, and survival outcomes between early-onset versus late-onset CRC patients were assessed by Chi-squared test and Cox models., Results: The study population included 1,061,204 patients, 108,058 (10.2%) of whom were under age 50. The proportion of patients diagnosed under age 50 increased over time: 9.4% in 2004-2006, 10.1% in 2007-2009, 10.5% in 2010-2012, and 10.7% in 2013-2015 (p < 0.0001). Early-onset CRC patients were more likely to be Black (15.1% vs. 11.3%) or Hispanic (8.6% vs. 4.6%) and to present with stage 4 disease (24.9% vs. 17.0%), p < 0.0001 for all. Black patients had the worst median OS (58.3 months) compared to White (67.0 months), Hispanic (91.6 months), or Asian (104.9 months) patients, p < 0.0001. Within the subgroup of early-onset CRC patients with private insurance, Black patients had worse OS compared to White patients, even in communities with higher income and education status., Conclusions: Early-onset CRC continues to increase. Patients with early-onset CRC are more likely to be Black or Hispanic and to present with stage 4 cancer. Early-onset Black patients showed worse OS compared to White patients in all income subgroups, even with private insurance., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Endoscopic submucosal dissection is an established advanced polypectomy technique to manage large colorectal polyps., Objective: The purpose of this study was to evaluate patients who had endoscopic submucosal dissection in the setting of significant scarring attributed to a previous intervention to determine whether this is safe and feasible., Design: The study used a prospectively maintained database., Settings: A scarred lesion was defined as a nonlifting polyp with a history of previous attempted removal with endoscopic mucosal resection, snare, or biopsy where there was no suspicion of malignancy., Patients: All consecutive patients in the previous 14 months were included., Intervention: Endoscopic submucosal dissection was the study intervention., Main Outcome Measures: Thirty-day morbidity and mortality, readmission, length of stay, and recurrence were measured., Results: Ninety-one patients had endoscopic submucosal dissection over a 14-month period with a median polyp size of 31.5 mm (range, 20-45 mm). Eleven patients (12%) were confirmed as having significant scar. There were significantly more previous endoscopic mucosal resections in the scarred group (scarred: 63.6% vs nonscarred: 2.5%; p < 0.001). Significantly more of the scarred patients had their endoscopic submucosal dissection in the operating room versus the endoscopy suite (scarred: 82.0% vs nonscarred: 17.5%; p < 0.001). The 30-day morbidity rate was 18.7%. There were no mortalities. There was no difference in 30-day morbidity between scarred and nonscarred lesions (scarred: 9% vs nonscarred: 20%; p = 0.4). There were more day-case procedures in the nonscarred group (nonscarred: 93.7% vs scarred: 36.4%; p < 0.001). There was no malignancy on final pathology in the scarred group. There was no difference in readmission rate between the scarred and nonscarred lesions. The overall follow-up colonoscopy rate was 53%, and there were no polyp recurrences identified., Limitations: The study was limited by its small sample size, single institute, surgeon experience, and short follow-up., Conclusions: Not only is endoscopic submucosal dissection in patients who have scarred lesions technically feasible and safe, it avoids a bowel resection in the majority of patients who have exhausted other advanced endoscopy techniques. See Video Abstract at http://links.lww.com/DCR/B427., Empujar El Sobre En La Diseccin Endoscpica Submucosa Es Factible Y Seguro En Lesiones Cicatrizadas: ANTECEDENTES:La disección endoscópica submucosa es una técnica de polipectomía avanzada establecida para tratar pólipos colorrectales grandes.OBJETIVO:Evaluar a pacientes que se sometieron a disección submucosa endoscópica en el contexto de cicatrices significativas debido a una intervención previa para determinar si esto es seguro y factible.DISEÑO:Base de datos mantenida prospectivamente.AJUSTE:Una lesión cicatrizada se definió como un pólipo que no se levanta con antecedentes de intento de extirpación previa con resección endoscópica de la mucosa, lazo o biopsia, donde no había sospecha de malignidad.PACIENTES:Todos los pacientes consecutivos en los últimos 14 meses.INTERVENCIÓN:Disección submucosa endoscópica.MEDIDAS DE RESULTADOS PRINCIPALES:Morbilidad y mortalidad a 30 días, reingreso, duración de la estadía, recurrencia.RESULTADOS:Noventa y un pacientes tuvieron disección submucosa endoscópica durante un período de 14 meses con tamaño de pólipo mediana de 31,5 mm (rango, 20 - 45 mm). Se confirmó que once pacientes (12%) tenían una cicatriz significativa. Hubo significativamente más resecciones de mucosa endoscópica previas en el grupo con cicatrices (con cicatrices: 63,6% vs. sin cicatrices: 2,5%, p <0,001). Significativamente más de los pacientes con cicatrices tuvieron su disección submucosa endoscópica en el quirófano en comparación con la sala de endoscopia (con cicatrices: 82% vs. sin cicatrices: 17.5%, p <0.001). La tasa de morbilidad a 30 días fue del 18,7%. No hubo muertes. No hubo diferencia en la morbilidad a 30 días entre las lesiones cicatrizadas y no cicatrizadas (cicatrizadas: 9% frente a no cicatrizadas: 20%, p = 0,4). Hubo más procedimientos ambulatorios en el grupo sin cicatrices (sin cicatrices: 93,7% frente a cicatrices: 36,36%, p <0,001). No hubo malignidad en la patología final en el grupo con cicatrices. No hubo diferencia en la tasa de reingreso entre las lesiones cicatrizadas y no cicatrizadas. La tasa general de colonoscopia de seguimiento fue del 53% y no se identificaron recurrencias de pólipos.LIMITACIONES:Tamaño de muestra pequeño, experiencia de un solo instituto y cirujanos y seguimiento corto.CONCLUSIÓN:La disección endoscópica submucosa en pacientes con lesiones cicatrizadas no solo es técnicamente factible y segura, sino que evita una resección intestinal en la mayoría de los pacientes que han agotado otras técnicas endoscópicas avanzadas. Consulte Video Resumen en http://links.lww.com/DCR/B427., (Copyright © The ASCRS 2020.)

Background: Modified frailty index (mFI) has been proposed as a reliable tool in predicting postoperative outcomes after surgery. This study aims to evaluate whether mFI could be utilized to predict readmissions after colorectal resection for patients with cancer by using nationwide cohort., Methods: Patients undergoing elective abdominal colorectal resection for colorectal cancer were reviewed from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) procedure-targeted database (2010-2012). A previously described mFI was calculated. Demographics, comorbidities, and 30-day postoperative complications were compared between patients who were readmitted or not after colorectal surgery., Results: A total of 7337 patients were identified with a mean age of 65.8(±13.6) years. Eight hundred seventy-one (11.8%) patients were readmitted at least once within 30 days. Age, gender, BMI, and other comorbidities were comparable between the groups. O approach, current smoking, mFI(>3/11), disseminating cancer, bleeding disorder and longer operative time were found to independently associated with readmission., Conclusions: An 11-point modified frailty index as measured in NSQIP correlates with readmissions after colorectal resection in patients with colon and rectal cancer., Competing Interests: Declaration of competing interest The authors have no conflicts of interest or financial ties to disclose., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to determine the impact of the incision used for specimen extraction on wound infection during laparoscopic colorectal surgery., Methods: All patients undergoing elective laparoscopic colorectal resection in a single specialized department from 2000 to 2011 were identified from a prospectively maintained institutional database. Specific extraction-sites and other relevant factors associated with wound infection rates were evaluated with univariate and multivariate analyses., Results: 2801 patients underwent specimen extraction through infra-umbilical midline (N = 657), RLQ/LLQ (N = 388), stoma site (N = 58), periumbilical midline (N = 629), Pfannenstiel (N = 789) and converted midline (N = 280). The overall wound infection rate was 10% and was highest in converted midline (14.6%) and Pfannenstiel (11.4%) incisions, while the lowest rate was associated with RLQ/LLQ (N = 13, 3.3%). Independent factors associated with wound infection were increased BMI (p < 0.001), extraction site location (p = 0.006), surgical procedure (p = 0.020, particularly left-sided colectomy and total proctocolectomy), diagnosis (p < 0.001, particularly sigmoid diverticulitis and inflammatory bowel disease), intraabdominal adhesions (p = 0.033) and intrabdominal rather than pelvic procedure (p = 0.005)., Conclusions: A RLQ/LLQ extraction site is associated with the most reduced risk of wound infection in laparoscopic colorectal surgery., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Limited data on the relationship between postoperative complications (POCs) after colorectal cancer resection and oncologic outcomes are available. We hypothesized that the increased severity of POCs is associated with progressively worse oncologic outcomes., Methods: Patients with pathological stages I-III colorectal adenocarcinoma undergoing elective curative resection in a single institution between 2000 and 2012 were identified from a prospectively collected database. The severity of POCs was determined using the Clavien-Dindo classification, and oncologic outcomes were assessed., Results: Of 2266 patients, 669 (30%) had at least one POC. POCs were not associated with pathologic stage (p = 0.58) or use of adjuvant therapy (p = 0.19). With a mean follow-up of 5.3 years, POCs were associated with decreased 5-year overall survival (OS) (60% vs. 77%, p < 0.001), disease-free survival (DFS) (53% vs. 70%, p < 0.001), cancer-specific survival (CSS) (81% vs. 87%, p < 0.001), and increased overall recurrence rates (19% vs. 15%, p = 0.008). Increasing Clavien-Dindo scores from I to IV was significantly associated with progressively decreasing OS (71, 64, 60, 22%, p < 0.001), DFS (65, 58, 51, 19%, p < 0.001), CSS (88, 77, 79, 74%, p < 0.001), and increasing recurrence rates (12, 20, 26, 18%, p = 0.002). Multivariate analysis confirmed POCs as an independent factor associated with decreased OS [hazard ratio (HR) 0.63, 95% CI 0.52-0.76], DFS (HR 0.64, 95% CI 0.54-0.76), CSS (HR 0.73, 95% CI 0.56-0.97), and increased recurrence rates (HR 1.36, 95% CI 1.02-1.80)., Conclusions: POCs are associated with adverse oncologic outcomes, with increasing effect with higher Clavien-Dindo score. Efforts to reduce both the incidence and severity of complications should result in improved oncologic outcomes.

A main limitation of therapies that selectively target kinase signalling pathways is the emergence of secondary drug resistance. Cetuximab, a monoclonal antibody that binds the extracellular domain of epidermal growth factor receptor (EGFR), is effective in a subset of KRAS wild-type metastatic colorectal cancers. After an initial response, secondary resistance invariably ensues, thereby limiting the clinical benefit of this drug. The molecular bases of secondary resistance to cetuximab in colorectal cancer are poorly understood. Here we show that molecular alterations (in most instances point mutations) of KRAS are causally associated with the onset of acquired resistance to anti-EGFR treatment in colorectal cancers. Expression of mutant KRAS under the control of its endogenous gene promoter was sufficient to confer cetuximab resistance, but resistant cells remained sensitive to combinatorial inhibition of EGFR and mitogen-activated protein-kinase kinase (MEK). Analysis of metastases from patients who developed resistance to cetuximab or panitumumab showed the emergence of KRAS amplification in one sample and acquisition of secondary KRAS mutations in 60% (6 out of 10) of the cases. KRAS mutant alleles were detectable in the blood of cetuximab-treated patients as early as 10 months before radiographic documentation of disease progression. In summary, the results identify KRAS mutations as frequent drivers of acquired resistance to cetuximab in colorectal cancers, indicate that the emergence of KRAS mutant clones can be detected non-invasively months before radiographic progression and suggest early initiation of a MEK inhibitor as a rational strategy for delaying or reversing drug resistance.

Purpose: Cetuximab, an antibody targeting the epidermal growth factor receptor (EGFR), is active in colorectal cancer (CRC). However, response rates range from only 10% to 20%. Here, we investigate hepatocyte growth factor (HGF)-dependent mesenchymal-epithelial transition factor (MET) activation as a mediator of cetuximab resistance through signal diversification in CRC cell lines., Experimental Design: DiFi, GEO, and LIM1215 cells were treated with varying concentrations and combinations of EGF, HGF, cetuximab, and PHA-665752 (a highly specific MET kinase inhibitor). Biological end points included proliferation, cell cycle arrest, and apoptosis. Proliferation was measured using WST-1 assays and synergy investigated via isobolograms. Expression and signaling were examined using immunoblotting., Results: EGFR and MET are coexpressed in these CRC cell lines, and dual receptor activation synergistically increased proliferation. Cetuximab inhibited cell growth by 60%-80% with an associated dephosphorylation of EGFR, MAPK, and/or AKT. Addition of HGF to cetuximab-treated cells phosphorylated MET, but not EGFR or ErbB3, restimulated the MAPK and AKT pathways, restored cell proliferation, and rescued cells from G1 arrest and apoptosis. Importantly, this effect could be abrogated by inhibiting MET activation with PHA-665752 or by downregulating MET expression with RNAi., Conclusions: HGF-induced MET activation is a novel mechanism of cetuximab resistance in CRC. Inhibition of the HGF-MET pathway may improve response to EGFR inhibitors in CRC, and combination therapy should be further investigated., (©2010 AACR.)