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Background: Recent studies have suggested that certain combinations of KRAS or BRAF biomarkers with clinical factors are associated with poor outcomes and may indicate that surgery could be "biologically" futile in otherwise technically resectable colorectal liver metastasis (CRLM). However, these combinations have yet to be validated through external studies., Patients and Methods: We conducted a systematic search to identify these studies. The overall survival (OS) of patients with these combinations was evaluated in a cohort of patients treated at 11 tertiary centers. Additionally, the study investigated whether using high-risk KRAS point mutations in these combinations could be associated with particularly poor outcomes., Results: The recommendations of four studies were validated in 1661 patients. The first three studies utilized KRAS, and their validation showed the following median and 5-year OS: (1) 30 months and 16.9%, (2) 24.3 months and 21.6%, and (3) 46.8 months and 44.4%, respectively. When analyzing only patients with high-risk KRAS mutations, median and 5-year OS decreased to: (1) 26.2 months and 0%, (2) 22.3 months and 15.1%, and (3) not reached and 44.9%, respectively. The fourth study utilized BRAF, and its validation showed a median OS of 10.4 months, with no survivors beyond 21 months., Conclusion: The combinations of biomarkers and clinical factors proposed to render surgery for CRLM futile, as presented in studies 1 (KRAS high-risk mutations) and 4, appear justified. In these studies, there were no long-term survivors, and survival was similar to that of historic cohorts with similar mutational profiles that received systemic therapies alone for unresectable disease., Competing Interests: Disclosure. None to report., (© 2024. Society of Surgical Oncology.)

Background: Machine learning (ML) may provide novel insights into data patterns and improve model prediction accuracy. The current study sought to develop and validate an ML model to predict early extra-hepatic recurrence (EEHR) among patients undergoing resection of colorectal liver metastasis (CRLM)., Methods: Patients with CRLM who underwent curative-intent resection between 2000 and 2020 were identified from an international multi-institutional database. An eXtreme gradient boosting (XGBoost) model was developed to estimate the risk of EEHR, defined as extrahepatic recurrence within 12 months after hepatectomy, using clinicopathological factors. The relative importance of factors was determined using Shapley additive explanations (SHAP) values., Results: Among 1410 patients undergoing curative-intent resection, 131 (9.3%) patients experienced EEHR. Median OS among patients with and without EEHR was 35.4 months (interquartile range [IQR] 29.9-46.7) versus 120.5 months (IQR 97.2-134.0), respectively (p < 0.001). The ML predictive model had c-index values of 0.77 (95% CI, 0.72-0.81) and 0.77 (95% CI, 0.73-0.80) in the entire dataset and the validation data set with bootstrapping resamples, respectively. The SHAP algorithm demonstrated that T and N primary tumor categories, as well as tumor burden score were the three most important predictors of EEHR. An easy-to-use risk calculator for EEHR was developed and made available online at: https://junkawashima.shinyapps.io/EEHR/., Conclusions: An easy-to-use online calculator was developed using ML to help clinicians predict the chance of EEHR after curative-intent resection for CRLM. This tool may help clinicians in decision-making related to treatment strategies for patients with CRLM., (© 2024 The Author(s). World Journal of Surgery published by John Wiley & Sons Ltd on behalf of International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Background: Liver transplantation (LT) for nonresectable colorectal liver metastasis (NRCRLM) has become accepted for select patients meeting strict inclusion criteria. Advancements in patient selection and understanding of cancer biology may expand benefits to patients with colorectal liver metastasis (CRLM). In this meta-analysis, we sought to assess survival outcomes, recurrence patterns, and quality of life (QoL) after LT for CRLM., Methods: PubMed, Embase, and Scopus databases were searched. A random-effect meta-analysis was conducted to obtain pooled overall survival (OS) and disease-free survival (DFS) rates and to compare QoL from baseline. Continuous data were analyzed, and standardized mean differences were reported., Results: Overall, 16 studies (403 patients, 58.8% male sex) were included. The pooled 1-, 3-, and 5-year OS after LT for NRCRLM was 96% (95% CI: 92%-99%), 77% (95% CI: 62%-89%), and 53% (95% CI: 45%-61%), respectively. Moreover, the pooled 1-, 3-, and 5-year DFS was 58% (95% CI: 43%-72%), 33% (95% CI: 9%-61%), and 13% (95% CI: 4%-27%), respectively. Overall, 201 patients (49.8%) experienced recurrence during the follow-up period with the lungs being the most common site (45.8%). There was no significant differences in physical and emotional functioning, fatigue, and pain components of QoL at 6 months after LT compared with baseline (all P > .05)., Conclusion: LT for NRCRLM demonstrated good OS outcomes with no differences in the QoL at 6 months after transplantation. Transplantation may represent a viable treatment option for NRCRLM., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

Introduction: Accurate prediction of patients at risk for early recurrence (ER) among patients with colorectal liver metastases (CRLM) following preoperative chemotherapy and hepatectomy remains limited., Methods: Patients with CRLM who received chemotherapy prior to undergoing curative-intent resection between 2000 and 2020 were identified from an international multi-institutional database. Multivariable Cox regression analysis was used to assess clinicopathological factors associated with ER, and an online calculator was developed and validated., Results: Among 768 patients undergoing preoperative chemotherapy and curative-intent resection, 128 (16.7 %) patients had ER. Multivariable Cox analysis demonstrated that Eastern Cooperative Oncology Group Performance status ≥1 (HR 2.09, 95%CI 1.46-2.98), rectal cancer (HR 1.95, 95%CI 1.35-2.83), lymph node metastases (HR 2.39, 95%CI 1.60-3.56), mutated Kirsten rat sarcoma oncogene status (HR 1.95, 95%CI 1.25-3.02), increase in tumor burden score during chemotherapy (HR 1.51, 95%CI 1.03-2.24), and bilateral metastases (HR 1.94, 95%CI 1.35-2.79) were independent predictors of ER in the preoperative setting. In the postoperative model, in addition to the aforementioned factors, tumor regression grade was associated with higher hazards of ER (HR 1.91, 95%CI 1.32-2.75), while receipt of adjuvant chemotherapy was associated with lower likelihood of ER (HR 0.44, 95%CI 0.30-0.63). The discriminative accuracy of the preoperative (training: c-index: 0.77, 95%CI 0.72-0.81; internal validation: c-index: 0.79, 95%CI 0.75-0.82) and postoperative (training: c-index: 0.79, 95%CI 0.75-0.83; internal validation: c-index: 0.81, 95%CI 0.77-0.84) models was favorable (https://junkawashima.shinyapps.io/CRLMfollwingchemotherapy/)., Conclusions: Patient-, tumor- and treatment-related characteristics in the preoperative and postoperative setting were utilized to develop an online, easy-to-use risk calculator for ER following resection of CRLM., 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. No funding was received for this study., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: To date, only two studies have compared the outcomes of patients with liver-limited BRAF V600E-mutated colorectal liver metastases (CRLMs) managed with resection versus systemic therapy alone, and these have reported contradictory findings., Methods: In this observational, international, multicentre study, patients with liver-limited BRAF V600E-mutated CRLMs treated with resection or systemic therapy alone were identified from institutional databases. Patterns of recurrence/progression and overall survival were compared using multivariable analyses of the entire cohort and a propensity score-matched cohort., Results: Of 170 patients included, 119 underwent hepatectomy and 51 received systemic treatment. Surgically treated patients had a more favourable pattern of recurrence with most recurrences limited to a single site, whereas diffuse progression was more common among patients who received systemic treatment (19 versus 44%; P = 0.002). Surgically treated patients had longer median overall survival (35 versus 20 months; P < 0.001). Hepatectomy was independently associated with better OS than systemic treatment alone (HR 0.37, 95% c.i. 0.21 to 0.65). In the propensity score-matched cohort, surgically treated patients had longer median overall survival (28 versus 20 months; P < 0.001); hepatectomy was independently associated with better overall survival (HR 0.47, 0.25 to 0.88)., Conclusion: BRAF V600E mutation should not be considered a contraindication to surgery for patients with resectable, liver-only CRLMs., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Inflammatory bowel disease may affect the pathogenesis and clinicopathologic course of colorectal cancer. We sought to characterize the impact of inflammatory bowel disease on outcomes after colectomy and/or proctectomy for a malignant indication., Methods: Patients diagnosed with colorectal cancer as well as a pre-existing comorbid diagnosis of Crohn's disease or ulcerative colitis between 2018 and 2021 were identified from Medicare claims data. The postoperative textbook outcome was defined as the absence of complications, as well as no extended hospital stay, 90-day readmission, or mortality. Postdischarge disposition and expenditures were also examined., Results: Among 191,684 patients with colorectal cancer, 4,770 (2.5%) had a pre-existing diagnosis of inflammatory bowel disease. Patients with inflammatory bowel disease-associated colorectal cancer were less likely to undergo surgical resection (no inflammatory bowel disease: 47.6% vs inflammatory bowel disease: 42.1%; P < .001). Among patients who did undergo colorectal surgery, individuals with inflammatory bowel disease were less likely to achieve a textbook outcome (odds ratio 0.64 [95% confidence interval 0.58-0.70]). In particular, patients with inflammatory bowel disease had higher odds of postoperative complications (odds ratio 1.24 [1.12-1.38]), extended hospital stay (odds ratio 1.41 [1.27-1.58]), and readmission within 90 days (odds ratio 1.56 [1.42-1.72]) (all P < .05). Patients with inflammatory bowel disease-associated colorectal cancer were less likely to be discharged to their home under independent care (odds ratio 0.77 [0.68-0.87]) and had 12.2% higher expenditures, which correlated with whether the patient had a postoperative textbook outcome., Conclusion: One in 40 patients with colorectal cancer had concomitant inflammatory bowel disease. Inflammatory bowel disease was associated with a lower probability of achieving ideal postoperative outcomes, higher postdischarge expenditure, as well as worse long-term survival after colorectal cancer resection., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Health care providers play a crucial role in increasing overall awareness, screening, and treatment of cancer, leading to reduced cancer mortality. We sought to characterize the impact of provider density on colorectal cancer population-level mortality., Methods: County-level provider data, obtained from the Area Health Resource File between 2016 and 2018, were used to calculate provider density per county. These data were merged with county-level colorectal cancer mortality 2016-2020 data from the Centers for Disease Control and Prevention. Multivariable regression was performed to define the association between provider density and colorectal cancer mortality., Results: Among 2,863 counties included in the analytic cohort, 1,132 (39.5%) and 1,731 (60.5%) counties were categorized as urban and rural, respectively. The colorectal cancer-related crude mortality rate was higher in counties with low provider density versus counties with moderate or high provider density (low = 22.9, moderate = 21.6, high = 19.3 per 100,000 individuals; P < .001). On multivariable analysis, the odds of colorectal cancer mortality were lower in counties with moderate and high provider density versus counties with low provider density (moderate odds ratio 0.97, 95% confidence interval 0.94-0.99; high odds ratio 0.88, 95% confidence interval 0.86-0.91). High provider density remained associated with a lower likelihood of colorectal cancer mortality independent of social vulnerability index (low social vulnerability index and high provider density: odds ratio 0.85, 95% confidence interval 0.81-0.89; high social vulnerability index and high provider density: odds ratio 0.93, 95% confidence interval 0.89-0.98)., Conclusion: Regardless of social vulnerability index, high county-level provider density was associated with lower colorectal cancer-related mortality. Efforts to increase access to health care providers may improve health care equity, as well as long-term cancer outcomes., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: A survey of medical oncologists (MOs), radiation oncologists (ROs), and surgical oncologists (SOs) who are experts in the management of patients with metastatic colorectal cancer (mCRC) was conducted to identify factors used to consider metastasis-directed therapy (MDT)., Materials and Methods: An online survey to assess clinical factors when weighing MDT in patients with mCRC was developed based on systematic review of the literature and integrated with clinical vignettes. Supporting evidence from the systematic review was included to aid in answering questions., Results: Among 75 experts on mCRC invited, 47 (response rate 62.7%) chose to participate including 16 MOs, 16 ROs, and 15 SOs. Most experts would not consider MDT in patients with 3 lesions in both the liver and lung regardless of distribution or timing of metastatic disease diagnosis (6 vs. 36 months after definitive treatment). Similarly, for patients with retroperitoneal lymph node and lung and liver involvement, most experts would not offer MDT regardless of timing of metastatic disease diagnosis. In general, SOs were willing to consider MDT in patients with more advanced disease, ROs were more willing to offer treatment regardless of metastatic site location, and MOs were the least likely to consider MDT., Conclusions: Among experts caring for patients with mCRC, significant variation was noted among MOs, ROs, and SOs in the distribution and volume of metastatic disease for which MDT would be considered. This variability highlights differing opinions on management of these patients and underscores the need for well-designed prospective randomized trials to characterize the risks and potential benefits of MDT., Competing Interests: Disclosure Eric D. Miller, Kathryn E. Hitchcock, Paul B. Romesser, Sepideh Gholami are part of the study team for A022101, the ERASur trial. No other authors have interests to declare that are relevant to this work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Multivisceral resection of retroperitoneal liposarcoma (LPS) is associated with increased morbidity and may not confer a survival benefit compared with tumor-only (TO) resection. We compared both approaches using a novel statistical method called the "win ratio" (WR)., Methods: Patients who underwent resection of LPS from 2004 to 2015 were identified from the National Cancer Database. Multivisceral resection was defined as removal of the primary site in addition to other organs. The WR was calculated based on a hierarchy of postoperative outcomes: 30-day and 90-day mortality, long-term survival, and severe complication., Results: Among 958 patients (multivisceral 634, TO 324) who underwent resection, the median age was 63 years (interquartile range [IQR] 54-71) with a median follow-up of 51 months (IQR 30-86). There was no difference in the WR among patients who underwent TO versus multivisceral resection in the matched cohort (WR 0.82, 95% confidence interval [CI] 0.61-1.10). In patients aged 72-90 years, those who underwent multivisceral resection had 36% lower odds of winning compared with patients undergoing TO resection (WR 0.64, 95% CI 0.40-0.98). A subgroup analysis of patients classified as not having adjacent tumor involvement at the time of surgery revealed that those patients who underwent multivisceral resection had 33% lower odds of winning compared to TO resection (WR 0.67, 95% CI 0.45-0.99)., Conclusions: Based on win-ratio assessments of a hierarchical composite endpoint, multivisceral resection in patients without adjacent tumor involvement may not confer improved outcomes. This method supports the rationale for less invasive resection of LPS in select patients, especially older patients., (© 2024. The Author(s).)

Background: A large proportion of patients with colorectal cancer (CRC) presents with synchronous colorectal liver metastases (sCRLM) at diagnosis. Surgical approaches for patients with sCRLM have evolved over the past decades. Simultaneous resection (SR) of CRC and sCRLM for selected patients has emerged as a safe and efficient alternative approach to traditional staged resections., Methods: A comprehensive review of the literature was performed using MEDLINE/PubMed and Web of Science databases with the end of search date October 30, 2023. The MeSH terms "simultaneous resections" and "combined resections" in combination with "colorectal liver metastases," "colorectal cancer," "liver resection," and "hepatectomy" were searched in the title and/or abstract., Results: SRs aim to achieve maximal tumor clearance, minimizing the risk of disease progression and optimizing the potential for long-term survival. Improvements in perioperative care, advances in surgical techniques, and a better understanding of patient selection criteria have collectively contributed to reducing morbidity and mortality associated with these complex procedures. Several studies have demonstrated that SR are associated with reduced overall length of stay and lower costs with comparable morbidity and long-term outcomes. In light of these outcomes, the proportion of patients undergoing SR for CRC and sCRLM has increased substantially over the past 2 decades., Conclusion: For patients with sCRLM, SR represents an attractive alternative to the traditional staged approach and should be selectively used; however, the decision on whether to proceed with a simultaneous versus staged approach should be individualized based on several patient- and disease-related factors., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

Background: Food insecurity predisposes individuals to suboptimal nutrition, leading to chronic disease and poor outcomes., Objective: We sought to assess the impact of county-level food insecurity on colorectal surgical outcomes., Design: Retrospective cohort study., Setting: Data from the Surveillance, Epidemiology, and End Results-Medicare database was merged with county-level food insecurity obtained from the Feeding America: Mapping the Meal Gap report. Multiple logistic and Cox regression adjusted for patient-level covariates were implemented to assess outcomes., Patients: Medicare beneficiaries diagnosed with colorectal cancer between 2010 and 2015., Main Outcome Measures: Surgical admission type (nonelective and elective admission), any complication, extended length of stay, discharge disposition (discharged to home and nonhome discharge), 90-day readmission, 90-day mortality, and textbook outcome. Textbook outcome was defined as no extended length of stay, postoperative complications, 90-day readmission, and 90-day mortality., Results: Among 72,354 patients with colorectal cancer, 46,296 underwent resection. Within the surgical cohort, 9091 (19.3%) were in low, 27,716 (59.9%) were in moderate, and 9,489 (20.5%) were in high food insecurity counties. High food insecurity patients had greater odds of nonelective surgery (OR: 1.17; 95% CI, 1.09-1.26; p < 0.001), 90-day readmission (OR: 1.11; 95% CI, 1.04-1.19; p = 0.002), extended length of stay (OR: 1.32; 95% CI, 1.21-1.44; p < 0.001), and complications (OR: 1.11; 95% CI, 1.03-1.19; p = 0.002). High food insecurity patients also had decreased odds of home discharge (OR: 0.85; 95% CI, 0.79-0.91; p < 0.001) and textbook outcomes (OR: 0.81; 95% CI, 0.75-0.87; p < 0.001). High food insecurity minority patients had increased odds of complications (OR 1.59; 95% CI, 1.43-1.78) and extended length of stay (OR 1.89; 95% CI, 1.69-2.12) compared with low food insecurity white patients (all, p < 0.001). Notably, high food insecurity minority patients had 31% lower odds of textbook outcomes (OR: 0.69; 95% CI, 0.62-0.76; p < 0.001) compared with low food insecurity White patients ( p < 0.001)., Limitations: This study was limited to Medicare beneficiaries aged 65 years or older; hence, it may not be generalizable to younger populations or those without insurance or with private insurance., Conclusions: County-level food insecurity was associated with suboptimal outcomes, demonstrating the importance of interventions to mitigate these inequities. See Video Abstract., La Asociacin De Inseguridad Alimentaria Y Resultados Quirrgicos Entre Pacientes Sometidos a Ciruga De Cncer Colorrectal: ANTECEDENTES:La inseguridad alimentaria predispone a las personas a una nutrición subóptima, lo que conduce a enfermedades crónicas y malos resultados.OBJETIVO:Intentamos evaluar el impacto de la inseguridad alimentaria a nivel de condado en resultados de la cirugía colorrectal.DISEÑO:Estudio de cohorte retrospectivo.ENTORNO CLINICO:La base de datos SEER-Medicare fusionada con la inseguridad alimentaria a nivel de condado obtenida del informe Feeding America: Mapping the Meal Gap. Para evaluar los resultados se implementaron regresiones logísticas múltiples y de Cox ajustadas según las covariables a nivel de paciente.PACIENTES:Beneficiarios de Medicare diagnosticados con cáncer colorrectal entre 2010 y 2015.PRINCIPALES MEDIDAS DE RESULTADO:Tipo de ingreso quirúrgico (ingreso no electivo y electivo), cualquier complicación, duración prolongada de la estancia hospitalaria, disposición del alta (alta al domicilio y alta no domiciliaria), reingreso a los 90 días, mortalidad a los 90 días y resultado del libro de texto. El resultado de los libros de texto se definió como ausencia de estancia hospitalaria prolongada, complicaciones postoperatorias, reingreso a los 90 días y mortalidad a los 90 días.RESULTADOS:Entre 72.354 pacientes con cáncer colorrectal, 46.296 se sometieron a resección. Dentro de la cohorte quirúrgica, 9.091 (19,3%) tenían inseguridad alimentaria baja, 27.716 (59,9%) eran moderadas y 9.489 (20,5%) tenían inseguridad alimentaria alta. Los pacientes con alta inseguridad alimentaria tuvieron mayores probabilidades de cirugía no electiva (OR: 1,17, IC 95%: 1,09-1,26, p <0,001), reingreso a los 90 días (OR: 1,11, IC95%: 1,04-1,19, p = 0,002), duración prolongada de la estancia hospitalaria (OR: 1,32; IC95%: 1,21-1,44, p < 0,001) y complicaciones (OR: 1,11; IC95%: 1,03-1,19, p = 0,002). Los pacientes con alta inseguridad alimentaria también tuvieron menores probabilidades de ser dados de alta a domicilio (OR: 0,85, IC del 95%: 0,79-0,91, p <0,001) y resultados de los libros de texto (OR: 0,81, IC del 95%: 0,75-0,87, p <0,001). Los pacientes minoritarios con alta inseguridad alimentaria tuvieron mayores probabilidades de complicaciones (OR 1,59, IC 95%, 1,43-1,78) y duración prolongada de la estadía (OR 1,89, IC 95%, 1,69-2,12) en comparación con los individuos blancos con baja inseguridad alimentaria (todos, p < 0,001). En particular, los pacientes minoritarios con alta inseguridad alimentaria tenían un 31% menos de probabilidades de obtener resultados según los libros de texto (OR: 0,69, IC del 95%, 0,62-0,76, p <0,001) en comparación con los pacientes blancos con baja inseguridad alimentaria ( p <0,001).LIMITACIONES:Limitado a beneficiarios de Medicare mayores de 65 años, por lo tanto, puede no ser generalizable a poblaciones más jóvenes o a aquellos sin seguro o con seguro privado.CONCLUSIONES:La inseguridad alimentaria a nivel de condado se asoció con resultados subóptimos, lo que demuestra la importancia de las intervenciones para mitigar estas desigualdades. (Dr. Francisco M. Abarca-Rendon )., (Copyright © The ASCRS 2023.)

Background: Although some data suggest that patients with mutRAS colorectal liver metastases (CRLM) may benefit from anatomic hepatectomy, this topic remains controversial. We performed a systematic review and meta-analysis to determine whether RAS mutation status was associated with prognosis relative to surgical technique [anatomic resection (AR) vs. nonanatomic resection (NAR)] among patients with CRLM., Patients and Methods: A systematic review and meta-analysis of studies were performed to investigate the association of AR versus NAR with overall and liver-specific disease-free survival (DFS and liver-specific DFS, respectively) in the context of RAS mutation status., Results: Overall, 2018 patients (831 mutRAS vs. 1187 wtRAS) were included from five eligible studies. AR was associated with a 40% improvement in liver-specific DFS [hazard ratio (HR) = 0.6, 95% confidence interval (CI) 0.44-0.81, p = 0.01] and a 28% improvement in overall DFS (HR = 0.72, 95% CI 0.54-0.95, p = 0.02) among patients with mutRAS tumors; in contrast, AR was not associated with any improvement in liver-specific DFS or overall DFS among wtRAS patients. These differences may have been mediated by the 40% decreased incidence in R1 resection among patients with mutRAS tumors who underwent AR versus NAR [relative risk (RR): 0.6, 95% CI 0.40-0.91, p = 0.02]. In contrast, the probability of an R1 resection was not decreased among wtRAS patients who underwent AR versus NAR (RR: 0.93, 95% CI 0.69-1.25, p = 0.62)., Conclusions: The data suggest that precision surgery may be relevant to CRLM. Specifically, rather than a parenchymal sparing dogma for all patients, AR may have a role in individuals with mutRAS tumors., (© 2023. Society of Surgical Oncology.)

Background: Although systemic postoperative therapy after surgery for colorectal liver metastases is generally recommended, the benefit of adjuvant chemotherapy has been debated. We used machine learning to develop a decision tree and define which patients may benefit from adjuvant chemotherapy after hepatectomy for colorectal liver metastases., Methods: Patients who underwent curative-intent resection for colorectal liver metastases between 2000 and 2020 were identified from an international multi-institutional database. An optimal policy tree analysis was used to determine the optimal assignment of the adjuvant chemotherapy to subgroups of patients for overall survival and recurrence-free survival., Results: Among 1,358 patients who underwent curative-intent resection of colorectal liver metastases, 1,032 (76.0%) received adjuvant chemotherapy. After a median follow-up of 28.7 months (interquartile range 13.7-52.0), 5-year overall survival was 67.5%, and 3-year recurrence-free survival was 52.6%, respectively. Adjuvant chemotherapy was associated with better recurrence-free survival (3-year recurrence-free survival: adjuvant chemotherapy, 54.4% vs no adjuvant chemotherapy, 46.8%; P < .001) but no overall survival significant improvement (5-year overall survival: adjuvant chemotherapy, 68.1% vs no adjuvant chemotherapy, 65.7%; P = .15). Patients were randomly allocated into 2 cohorts (training data set, n = 679, testing data set, n = 679). The random forest model demonstrated good performance in predicting counterfactual probabilities of death and recurrence relative to receipt of adjuvant chemotherapy. According to the optimal policy tree, patient demographics, secondary tumor characteristics, and primary tumor characteristics defined the subpopulation that would benefit from adjuvant chemotherapy., Conclusion: A novel artificial intelligence methodology based on patient, primary tumor, and treatment characteristics may help clinicians tailor adjuvant chemotherapy recommendations after colorectal liver metastases resection., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: We sought to characterize the risk of postoperative complications relative to the surgical approach and overall synchronous colorectal liver metastases tumor burden score., Methods: Patients with synchronous colorectal liver metastases who underwent curative-intent resection between 2000 and 2020 were identified from an international multi-institutional database. Propensity score matching was employed to control for heterogeneity between the 2 groups. A virtual twins analysis was performed to identify potential subgroups of patients who might benefit more from staged versus simultaneous resection., Results: Among 976 patients who underwent liver resection for synchronous colorectal liver metastases, 589 patients (60.3%) had a staged approach, whereas 387 (39.7%) patients underwent simultaneous resection of the primary tumor and synchronous colorectal liver metastases. After propensity score matching, 295 patients who underwent each surgical approach were analyzed. Overall, the incidence of postoperative complications was 34.1% (n = 201). Among patients with high tumor burden scores, the surgical approach was associated with a higher incidence of postoperative complications; in contrast, among patients with low or medium tumor burden scores, the likelihood of complications did not differ based on the surgical approach. Virtual twins analysis demonstrated that preoperative tumor burden score was important to identify which subgroup of patients benefited most from staged versus simultaneous resection. Simultaneous resection was associated with better outcomes among patients with a tumor burden score <9 and a node-negative right-sided primary tumor; in contrast, staged resection was associated with better outcomes among patients with node-positive left-sided primary tumors and higher tumor burden score., Conclusion: Among patients with high tumor burden scores, simultaneous resection of the primary tumor and liver metastases was associated with an increased incidence of postoperative complications., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Metastatic colorectal cancer remains a deadly malignancy and is the third leading cause of cancer-related death. The mainstay of treatment for metastatic colorectal cancer is chemotherapy, but unfortunately, even with recent progress, overall survival is still poor. Colorectal cancer is a heterogeneous disease, and the underlying genetic differences among tumors can define the behavior and prognosis of the disease. Given the limitations of cytotoxic chemotherapy, research has focused on developing targeted therapy based on molecular subtyping. Since the early 2000s, multiple targeted therapies have demonstrated efficacy in treating metastatic colorectal cancer and have received FDA approval. The epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and DNA mismatch repair pathways have demonstrated promising results for targeted therapies. As new gene mutations and proteins involved in the oncogenesis of metastatic colorectal cancer are identified, new targets will continue to emerge. We herein provide a summary of the updated literature regarding targeted therapies for patients with mCRC.

Background: The internet is a common source of health information for patients. Interactive online artificial intelligence (AI) may be a more reliable source of health-related information than traditional search engines. This study aimed to assess the quality and perceived utility of chat-based AI responses related to 3 common gastrointestinal (GI) surgical procedures., Methods: A survey of 24 questions covering general perioperative information on cholecystectomy, pancreaticoduodenectomy (PD), and colectomy was created. Each question was posed to Chat Generative Pre-trained Transformer (ChatGPT) in June 2023, and the generated responses were recorded. The quality and perceived utility of responses were independently and subjectively graded by expert respondents specific to each surgical field. Grades were classified as "poor," "fair," "good," "very good," or "excellent.", Results: Among the 45 respondents (general surgeon [n = 13], surgical oncologist [n = 18], colorectal surgeon [n = 13], and transplant surgeon [n = 1]), most practiced at an academic facility (95.6%). Respondents had been in practice for a mean of 12.3 years (general surgeon, 14.5 ± 7.2; surgical oncologist, 12.1 ± 8.2; colorectal surgeon, 10.2 ± 8.0) and performed a mean 53 index operations annually (cholecystectomy, 47 ± 28; PD, 28 ± 27; colectomy, 81 ± 44). Overall, the most commonly assigned quality grade was "fair" or "good" for most responses (n = 622/1080, 57.6%). Most of the 1080 total utility grades were "fair" (n = 279, 25.8%) or "good" (n = 344, 31.9%), whereas only 129 utility grades (11.9%) were "poor." Of note, ChatGPT responses related to cholecystectomy (45.3% ["very good"/"excellent"] vs 18.1% ["poor"/"fair"]) were deemed to be better quality than AI responses about PD (18.9% ["very good"/"excellent"] vs 46.9% ["poor"/"fair"]) or colectomy (31.4% ["very good"/"excellent"] vs 38.3% ["poor"/"fair"]). Overall, only 20.0% of the experts deemed ChatGPT to be an accurate source of information, whereas 15.6% of the experts found it unreliable. Moreover, 1 in 3 surgeons deemed ChatGPT responses as not likely to reduce patient-physician correspondence (31.1%) or not comparable to in-person surgeon responses (35.6%)., Conclusions: Although a potential resource for patient education, ChatGPT responses to common GI perioperative questions were deemed to be of only modest quality and utility to patients. In addition, the relative quality of AI responses varied markedly on the basis of procedure type., (Copyright © 2023 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

Surgical resection is the cornerstone of treatment for metastatic colorectal cancer (CRC) and offers the best chance at long-term survival. Unfortunately, most patients do not present with resectable metastatic disease and, among patients who do undergo curative-intent resection, many will develop recurrence. In turn, patients require a multi-disciplinary treatment approach with a combination of chemotherapy, surgery, radiation, and/or liver directed therapies that is guided by patient disease burden and clinical status. The development of targeted therapies has led to varying success in other cancers and has emerged as a treatment option for patients with metastatic CRC. While cytotoxic chemotherapy aims to kill cells as they replicate, targeted therapies are directed at biologic features of cancers, like angiogenesis or immune checkpoints. Targeted therapy can facilitate a more treatment tailored approach to the unique genomic alterations of the tumor and hopefully deliver more personalized therapy. We herein provide a systematic review of approved targeted therapies and immune checkpoint inhibitors for metastatic CRC and provide an overview of the current literature., Competing Interests: Declaration of competing interest There are no conflicts of interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Benchmarking is a process of continuous self-evaluation and comparison with best-in-class hospitals to guide quality improvement initiatives. We sought to define global benchmarks relative to liver resection for malignancy and to assess their achievement in hospitals in the United States., Methods: Patients who underwent curative-intent liver resection for hepatocellular carcinoma, intrahepatic cholangiocarcinoma, or colorectal or neuroendocrine liver metastases between 2000 and 2019 were identified from an international multi-institutional database. Propensity score matching was conducted to balance baseline characteristics between open and minimally invasive approaches. Best-in-class hospitals were defined relative to the achievement rate of textbook oncologic outcomes and case volume. Benchmark values were established relative to best-in-class institutions. The achievement of benchmark values among hospitals in the National Cancer Database was then assessed., Results: Among 2,624 patients treated at 20 centers, a majority underwent liver resection for hepatocellular carcinoma (n = 1,609, 61.3%), followed by colorectal liver metastases (n = 650, 24.8%), intrahepatic cholangiocarcinoma (n = 299, 11.4%), and neuroendocrine liver metastases (n = 66, 2.5%). Notably, 1,947 (74.2%) patients achieved a textbook oncologic outcome. After propensity score matching, 6 best-in-class hospitals with the highest textbook oncologic outcome rates (≥75.0%) were identified. Benchmark values were calculated for margin positivity (≤11.7%), 30-day readmission (≤4.1%), 30-day mortality (≤1.6%), minor postoperative complications (≤24.7%), severe complications (≤12.4%), and failure to achieve the textbook oncologic outcome (≤22.8%). Among the National Cancer Database hospitals, global benchmarks for margin positivity, 30-day readmission, 30-day mortality, severe complications, and textbook oncologic outcome failure were achieved in 62.9%, 27.1%, 12.1%, 7.1%, and 29.3% of centers, respectively., Conclusion: These global benchmarks may help identify hospitals that may benefit from quality improvement initiatives, aiming to improve patient safety and surgical oncologic outcomes., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Surgical resection is typically necessary for curative-intent treatment of most solid organ cancers. However, even with meticulous preoperative evaluation, operative procedures are occasionally aborted. The incidence, outcomes, and long-term prognoses of aborted cancer surgery have not been thoroughly investigated., Methods: All oncologic operations performed at a single tertiary cancer center between 2011-2021 were retrospectively queried; natural language processing of operative reports was used to identify aborted cancer surgeries. Surgical indications, clinicopathologic characteristics, short- and long-term outcomes, and palliative care involvement were retrospectively reviewed from the electronic medical record., Results: Overall, 345 patients underwent aborted cancer surgery for a rate of 36 patients per year. The most common cancers were pancreatic (28%), biliary (14%), and colorectal (9%). The most commonly aborted operations were pancreatoduodenectomy (34%) and hepatectomy (22%). Most operations were aborted due to unanticipated tumor unresectability (47%) and occult metastatic disease (43%). Sixty percent of patients returned to cancer-directed therapy; 9% underwent successful reattempt at resection. The median overall survival of all patients after aborted surgery was 13.6 months (95% confidence interval, 11.2-16.0 months). Those who returned to oncologic therapy had longer survival (18.6 months vs 5.4 months, P < .001). Palliative care consultation was received by 34% and 13% of patients overall and within 30 days of surgery, respectively., Conclusion: Aborted cancer surgery was associated with poor outcomes, particularly in patients with aggressive cancer types and those who did not receive further cancer-directed therapy. Future studies should identify interventions such as palliative care consultation that may improve patient-centered outcomes., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Bilobar liver metastases from colorectal cancer pose a challenge for obtaining a satisfactory oncological outcome with an adequate future liver remnant. This study aimed to assess the clinical and pathological determinants of overall survival and recurrence-free survival among patients undergoing surgical clearance of bilobar liver metastases from colorectal cancer., Methods: A retrospective international multicentre study of patients who underwent surgery for bilobar liver metastases from colorectal cancer between January 2012 and December 2018 was conducted. Overall survival and recurrence-free survival at 1, 2, 3 and 5 years after surgery were the primary outcomes evaluated. The secondary outcomes were duration of postoperative hospital stay, and 90-day major morbidity and mortality rates. A prognostic nomogram was developed using covariates selected from a Cox proportional hazards regression model, and internally validated using a 3:1 random partition into derivation and validation cohorts., Results: A total of 1236 patients were included from 70 centres. The majority (88 per cent) of the patients had synchronous liver metastases. Overall survival at 1, 2, 3 and 5 years was 86.4 per cent, 67.5 per cent, 52.6 per cent and 33.8 per cent, and the recurrence-free survival rates were 48.7 per cent, 26.6 per cent, 19.2 per cent and 10.5 per cent respectively. A total of 25 per cent of patients had recurrent disease within 6 months. Margin positivity and progressive disease at liver resection were poor prognostic factors, while adjuvant chemotherapy in margin-positive resections improved overall survival. The bilobar liver metastases from colorectal cancer-overall survival nomogram was developed from the derivation cohort based on pre- and postoperative factors. The nomogram's ability to forecast overall survival at 1, 2, 3 and 5 years was subsequently validated on the validation cohort and showed high accuracy (overall C-index = 0.742)., Conclusion: Despite the high recurrence rates, overall survival of patients undergoing surgical resection for bilobar liver metastases from colorectal cancer is encouraging. The novel bilobar liver metastases from colorectal cancer-overall survival nomogram helps in counselling and informed decision-making of patients planned for treatment of bilobar liver metastases from colorectal cancer., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd.)

Objective: To investigate the clinical implications of BRAF -mutated (mut BRAF ) colorectal liver metastases (CRLMs)., Background: The clinical implications of mut BRAF status in CRLMs are largely unknown., Methods: Patients undergoing resection for mut BRAF CRLM were identified from prospectively maintained registries of the collaborating institutions. Overall survival (OS) and recurrence-free survival (RFS) were compared among patients with V600E versus non-V600E mutations, KRAS/BRAF comutation versus mut BRAF alone, microsatellite stability status (Microsatellite Stable (MSS) vs instable (MSI-high)), upfront resectable versus converted tumors, extrahepatic versus liver-limited disease, and intrahepatic recurrence treated with repeat hepatectomy versus nonoperative management., Results: A total of 240 patients harboring BRAF -mutated tumors were included. BRAF V600E mutation was associated with shorter OS (30.6 vs 144 mo, P =0.004), but not RFS compared with non-V600E mutations. KRAS/BRAF comutation did not affect outcomes. MSS tumors were associated with shorter RFS (9.1 vs 26 mo, P <0.001) but not OS (33.5 vs 41 mo, P =0.3) compared with MSI-high tumors, whereas patients with resected converted disease had slightly worse RFS (8 vs 11 mo, P =0.01) and similar OS (30 vs 40 mo, P =0.4) compared with those with upfront resectable disease. Patients with extrahepatic disease had worse OS compared with those with liver-limited disease (8.8 vs 40 mo, P <0.001). Repeat hepatectomy after intrahepatic recurrence was associated with improved OS compared with nonoperative management (41 vs 18.7 mo, P =0.004). All results continued to hold true in the multivariable OS analysis., Conclusions: Although surgery may be futile in patients with BRAF -mutated CRLM and concurrent extrahepatic disease, resection of converted disease resulted in encouraging survival in the absence of extrahepatic spread. Importantly, second hepatectomy in select patients with recurrence was associated with improved outcomes. Finally, MSI-high status identifies a better prognostic group, with regard to RFS while patients with non-V600E mutations have excellent prognosis., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Approximately 15% of patients experience a resectable intrahepatic recurrence after an index curative-intent hepatectomy for colorectal liver metastases (CRLM). We sought to investigate the impact of recurrence timing and tumor burden score (TBS) at the time of recurrence on overall survival among patients undergoing repeat hepatectomy., Methods: Patients with CRLM who experienced recurrent intrahepatic disease after initial hepatectomy between 2000 and 2020 were identified from an international multi-institutional database. The impact of time-TBS, defined as TBS divided by the time interval of recurrence, was assessed relative to overall survival., Results: Among 220 patients, the median age was 60.9 years (interquartile range [IQR]: 53.0-69.0), and 144 (65.5%) patients were male. Most patients experienced multiple recurrences (n = 120, 54.5%) within 12 months after the initial hepatectomy (n = 139, 63.2%). The median tumor size of the recurrent CRLM was 2.2 cm (IQR: 1.5-3.0 cm) with a median TBS of 3.5 (2.3-4.9) at the time of recurrence. Overall, 121 (55.0%) patients underwent repeat hepatectomy, whereas 99 (45.0%) individuals were treated with systemic chemotherapy or other nonsurgical treatments; repeat hepatectomy was associated with better postrecurrence survival (PRS) (p < 0.001). Three-year PRS incrementally worsened (low time-TBS: 71.7%, 95% confidence interval [CI], 57.9-88.8 vs. medium: 63.6%, 95% CI, 47.7-84.8 vs. high: 49.2%, 95% CI, 31.1-77.7, p = 0.02) as time-TBS values increased. Each unit increase in time-TBS score was independently associated with a 41% higher possibility of death (hazard ratio: 1.41; 95% CI, 1.04-1.90, p = 0.03)., Conclusions: Time-TBS was associated with long-term outcomes after repeat hepatectomy for recurrent CRLM. Time-TBS may be an easy tool to help select patients who may benefit the most from repeat hepatic resection of recurrent CRLM., (© 2023 Wiley Periodicals LLC.)

The liver is the most frequently target for metastasis among patients with colorectal cancer mainly because of the portal vein circulation that directly connects the colon and rectum with the liver. The liver tumor microenvironment consists of different cell types each with unique characteristics and functions that modulate the antigen recognition and immune system activation. Primary tumors from other sites "prime" the liver prior to the seeding of cancer cells, creating a pre-metastatic niche. Following invasion into the liver, four different phases are key to the development of liver metastases: a microvascular phase in which cancer cells infiltrate and become trapped in sinusoidal vessels; an extravascular, pre-angiogenic phase; an angiogenic phase that supplies oxygen and nutrients to cancer cells; and a growth phase in which metastatic cells multiply and enlarge to form detectable tumors. Exosomes carry proteins, lipids, as well as genetic information that can create a pre-metastatic niche in distant sites, including the liver. The complexity of angiogenic mechanisms and the exploitation of the vasculature in situ by cancer cells have limited the efficacy of currently available anti-angiogenic therapies. Delineating the molecular mechanisms implicated in colorectal liver metastases is crucial to understand and predict tumor progression; the development of distant metastases; and resistance to chemotherapy, immunotherapy, and targeted treatment.

Background: Area-level social determinants of health (SDoH) impact access to cancer care and prevention. Little is known about the factors that underlie the impact of residential privilege on county-level cancer screening uptake., Methods: Population-based cross-sectional study examining county-level data was obtained from the Centers for Disease Control and Prevention's PLACES database, American Community Survey and the County Health Rankings and Roadmap database. The Index of Concentration of Extremes (ICE), a validated measure of racial and economic privilege, was examined relative to county-level rates of US Preventive Services Task Force (USPSTF) guideline-concordant screening for breast, cervical, and colorectal cancers. Generalized structural equation modeling was used to determine the indirect and direct effects of ICE on cancer screening uptake., Results: Across 3142 counties, county-level cancer screening rates demonstrated geographical variation ranging from 54.0% to 81.8% for breast cancer screening, from 39.8% to 74.4% for colorectal cancer screening, and from 69.9% to 89.7% for cervical cancer screening. Of note, cancer screening rates for breast, colorectal, and cervical cancer all increased from lower (ICE-Q1) to higher (ICE-Q4) privileged areas (breast: Q1 = 71.0% vs. Q4 = 72.2%; colorectal: Q1 = 59.4% vs. Q4 = 65.0%; cervical: Q1 = 83.3% vs. Q4 = 85.2%; all p < 0.001). Mediation analysis revealed that the observed disparities between ICE and cancer screening uptake were explained by mediators such as poverty status, lack of health insurance or employment, urban-rural location and access to primary care physicians that accounted for 64% (95% confidence interval [CI]: 61%-67%), 85% (95% CI: 80%-89%), and 74% (95% CI: 71%-77%) of the effect on breast, colorectal, and cervical cancer screening, respectively., Conclusions: In this cross-sectional study, the association between racial and economic privilege on USPSTF-recommended cancer screening was complex and influenced by an interplay of sociodemographic, geographical, and structural factors. Understanding the underlying area-level SDoH that mediate disparities in cancer prevention strategies can help focus interventions to improve equity in cancer prevention., (© 2023 Wiley Periodicals LLC.)

Introduction: Almost one-third of patients with colorectal cancer (CRC) experience recurrence after resection. Adherence to surveillance guidelines largely dictates efficacy in early detection of recurrence. We sought to assess and compare adherence to postoperative surveillance guidelines for colonoscopy, imaging, and Carcinoembryonic Antigen (CEA)., Methods: PubMed, Medline, Embase, Scopus, Cochrane, Web of Science, and CINAHL were systematically searched. Random-effects meta-analysis was performed and pooled adherence to each surveillance strategy was assessed for CEA, imaging, and colonoscopy., Results: Overall 14 studies (55,895 patients) met the inclusion criteria. Adherence to colonoscopy guidelines was the highest (70%, 95%CI 67-73), followed by imaging (63%, 95%CI 47-80), and CEA (54%; 95%CI 42-66). Among 7 (50%) studies that examined adherence to the American Society of Clinical Oncology guidelines, compliance with colonoscopy was the highest (73%; 95% CI 70-76), followed by imaging (58%; 95% CI 37-78), and CEA (45%; 95%CI 37-52). Of note, guideline adherence to CEA testing was much lower than colonoscopy among patients with colon (OR 0.21; 95%CI 0.20-0.22) and rectal cancer (OR 0.25; 95%CI 0.23-0.28) (both p < 0.05). This was also noted when compared with imaging recommendations among older patients (OR = 0.62; 95%CI 0.42-0.93) and patients with stage II, (OR = 0.80; 95%CI 0.76-0.84) and stage III disease (OR = 0.88; 95%CI 0.82-0.94) (all p < 0.05)., Conclusion: While guideline adherence to postoperative surveillance with colonoscopy was high, adherence to CEA testing and imaging surveillance strategies was markedly lower following CRC resection. Future studies should investigate avenues to improve compliance with surveillance guidelines among health care providers and patients to optimize postoperative follow-up for CRC., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: In order to investigate the optimal approach for synchronous colorectal liver metastases (sCRLM), we sought to use the "win ratio" (WR), a novel statistical approach, to assess the relative benefit of simultaneous versus staged surgical treatment., Methods: Patients who underwent hepatectomy for sCRLM between 2008 and 2020 were identified from a multi-institutional database. The WR approach was utilized to compare composite outcomes of patients undergoing simultaneous versus staged resection., Results: Among 1116 patients, 642 (57.5%) presented with sCRLM; 290 (45.2%) underwent simultaneous resection, while 352 (54.8%) underwent staged resection. In assessing the composite outcome, staged resection yielded a WR of 1.59 (95%CI 1.47-1.71) over the simultaneous approach for sCRLM. The highest WR occurred among patients requiring major hepatectomy (WR = 1.93, 95%CI 1.77-2.10) compared with patients who required minor liver resection (WR = 1.55, 95%CI 1.44-1.70)., Conclusions: Staged resection was superior to simultaneous resection for sCRLM based on a WR assessment., 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: Almost one-third of colorectal cancer (CRC) patients experience recurrence after resection; nevertheless, follow-up strategies remain controversial. We sought to systematically assess and compare the accuracy of carcinoembryonic antigen (CEA), imaging [positron emission tomography (PET) and computed tomography (CT) scans], and circulating tumor DNA (CtDNA) as surveillance strategies., Patients and Methods: PubMed, Medline, Embase, Scopus, Cochrane, Web of Science, and CINAHL were systematically searched. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used to assess methodological quality. We performed a bivariate random-effects meta-analysis and reported pooled sensitivity, specificity, and diagnostic odds ratio (DOR) values for each surveillance strategy., Results: Thirty studies were included in the analysis. PET scans had the highest sensitivity to detect recurrence (0.95; 95%CI 0.91-0.97), followed by CT scans (0.77; 95%CI 0.67-0.85). CtDNA positivity had the highest specificity to detect recurrence (0.95; 95%CI 0.91-0.97), followed by increased CEA levels (0.88; 95%CI 0.82-0.92). Furthermore, PET scans had the highest DOR to detect recurrence (DOR 120.7; 95%CI 48.9-297.9) followed by CtDNA (DOR 37.6; 95%CI 20.8-68.0)., Conclusion: PET scans had the highest sensitivity and DOR to detect recurrence, while CtDNA had the highest specificity and second highest DOR. Combinations of traditional cross-sectional/functional imaging and newer platforms such as CtDNA may result in optimized surveillance of patients following resection of CRC., (© 2022. Society of Surgical Oncology.)

Background: Liver-directed therapies (LDT) are important components of the multidisciplinary care of patients with colorectal cancer liver metastases (CRCLM) that contribute to improved long-term outcomes. Factors associated with receipt of LDT are poorly understood., Patients and Methods: Patients > 65 years old diagnosed with CRCLM were identified within the Medicare Standard Analytic File (2013-2017). Patients with extrahepatic metastatic disease were excluded. Mixed-effects analyses were used to assess patient factors associated with the primary outcome of LDT, defined as hepatectomy, ablation, and/or hepatic artery infusion chemotherapy (HAIC), as well as the secondary outcome of hepatectomy., Results: Among 23,484 patients with isolated CRCLM, only 2004 (8.5%) received LDT, although resectability status could not be determined for the entire cohort. Among patients who received LDT, 61.7% underwent hepatectomy alone, 28.1% received ablation alone, 8.5% underwent hepatectomy and ablation, and 1.8% received HAIC either alone (0.8%) or in combination with hepatectomy and/or ablation (0.9%). Patient factors independently associated with lower odds of LDT included older age, female sex, Black race, greater comorbidity burden, higher social vulnerability index, primary rectal cancer, synchronous liver metastasis, and further distance from a high-volume liver surgery center (p < 0.05). Results were similar for receipt of hepatectomy., Conclusions: Despite the well-accepted role of LDT for CRCLM, only a small proportion of Medicare beneficiaries with CRCLM receive LDT. Increasing access to specialized centers with expertise in LDT, particularly for Black patients, female patients, and those with higher levels of social vulnerability or long travel distances, may improve outcomes for patients with CRCLM., (© 2022. Society of Surgical Oncology.)

Introduction: Little is known about the societal burden of cancer surgical care in terms of out-of-pocket (OOP) costs. The current study sought to define OOP costs incurred by patients undergoing colorectal cancer resection., Methods: Privately insured patients undergoing colorectal cancer resection between 2013 and 2017 were identified from the IBM MarketScan database. Total and OOP costs were calculated within 1 year prior to and 1 year post surgery. A multivariable linear regression model was used to estimate total OOP costs relative to patient demographic and clinical characteristics., Results: Among 10,935 patients, 7289 (66.7%) had primary colon cancer while 3643 (33.3%) had rectal cancer. Median total costs were US$93,967 (IQR US$51027-168,251). Median OOP costs were US$4417 (IQR US$2519-6943), or 4.5% (IQR 2.2-8.1%) of total costs. OOP costs varied over the course of patient care; specifically, median OOP costs in the preoperative period were US$432 (IQR US$130-1452) versus US$2146 (IQR US$851-3525) in the perioperative period and US$969 (IQR US$327-2239) in the postoperative period. On multivariable analysis, receipt of chemotherapy (+US$1368, 95%CI +US$1211 to +US$1525) or radiotherapy (+US$842, 95% CI +US$626 to +US$1059) was associated with higher total OOP costs. Patients with a health maintenance organization (HMO) (-US$2119, 95% CI -US$2550 to -US$1689) or a point-of-service plan (-US$938, 95% CI -US$1385 to -US$491) had lower total OOP costs than patients with comprehensive insurance. In contrast, patients with a consumer-driven or a high-deductible health plan had considerably higher total OOP costs than patients with comprehensive insurance (+US$1400, 95% CI +US$972 to +US$1827 and +US$3243, 95% CI +US$2767 to +US$3717, respectively)., Conclusions: Privately insured colorectal cancer patients undergoing surgical resection pay a median of US$4417 in OOP costs, or 4.5% of total costs. OOP costs varied with receipt of chemotherapy or radiotherapy, region of residence, and insurance plan type., (© 2022. Society of Surgical Oncology.)

Importance: In patients with resectable colorectal cancer liver metastases (CRLM), the choice of surgical technique and resection margin are the only variables that are under the surgeon's direct control and may influence oncologic outcomes. There is currently no consensus on the optimal margin width., Objective: To determine the optimal margin width in CRLM by using artificial intelligence-based techniques developed by the Massachusetts Institute of Technology and to assess whether optimal margin width should be individualized based on patient characteristics., Design, Setting, and Participants: The internal cohort of the study included patients who underwent curative-intent surgery for KRAS-variant CRLM between January 1, 2000, and December 31, 2017, at Johns Hopkins Hospital, Baltimore, Maryland, Memorial Sloan Kettering Cancer Center, New York, New York, and Charité-University of Berlin, Berlin, Germany. Patients from institutions in France, Norway, the US, Austria, Argentina, and Japan were retrospectively identified from institutional databases and formed the external cohort of the study. Data were analyzed from April 15, 2019, to November 11, 2021., Exposures: Hepatectomy., Main Outcomes and Measures: Patients with KRAS-variant CRLM who underwent surgery between 2000 and 2017 at 3 tertiary centers formed the internal cohort (training and testing). In the training cohort, an artificial intelligence-based technique called optimal policy trees (OPTs) was used by building on random forest (RF) predictive models to infer the margin width associated with the maximal decrease in death probability for a given patient (ie, optimal margin width). The RF component was validated by calculating its area under the curve (AUC) in the testing cohort, whereas the OPT component was validated by a game theory-based approach called Shapley additive explanations (SHAP). Patients from international institutions formed an external validation cohort, and a new RF model was trained to externally validate the OPT-based optimal margin values., Results: This cohort study included a total of 1843 patients (internal cohort, 965; external cohort, 878). The internal cohort included 386 patients (median [IQR] age, 58.3 [49.0-68.7] years; 200 men [51.8%]) with KRAS-variant tumors. The AUC of the RF counterfactual model was 0.76 in both the internal training and testing cohorts, which is the highest ever reported. The recommended optimal margin widths for patient subgroups A, B, C, and D were 6, 7, 12, and 7 mm, respectively. The SHAP analysis largely confirmed this by suggesting 6 to 7 mm for subgroup A, 7 mm for subgroup B, 7 to 8 mm for subgroup C, and 7 mm for subgroup D. The external cohort included 375 patients (median [IQR] age, 61.0 [53.0-70.0] years; 218 men [58.1%]) with KRAS-variant tumors. The new RF model had an AUC of 0.78, which allowed for a reliable external validation of the OPT-based optimal margin. The external validation was successful as it confirmed the association of the optimal margin width of 7 mm with a considerable prolongation of survival in the external cohort., Conclusions and Relevance: This cohort study used artificial intelligence-based methodologies to provide a possible resolution to the long-standing debate on optimal margin width in CRLM.

Background: Prognostic stratification of patients with colorectal cancer liver metastasis based solely on tumor-related factors has only moderate discriminatory ability. We hypothesized that the inclusion of nontumor related factors can improve prediction of long-term prognosis of patients with colorectal cancer liver metastasis., Methods: Nontumor related laboratory markers were assessed utilizing a training cohort from 2 U.S. institutions (n = 1,205). Factors independently associated with prognosis were used to develop a nontumor related prognostic score. The discriminatory ability, assessed by Harrell's C-statistics (C-index) and net reclassification improvement, was validated and compared with 3 commonly used tumor-related clinical risk scores: Fong clinical risk scores, m-clinical risk scores, and Genetic and Morphological Evaluation (GAME) score in an external validation cohort from 5 Asian (n = 1,307) and 3 European (n = 1,058) institutions. The discriminatory ability of nontumor related prognostic score combined with each of these 3 tumor-related prognostic scores was also estimated., Results: Alkaline phosphatase (hazard ratio 1.43; 95% confidence interval, 1.11-1.84), albumin (hazard ratio 0.71; 95% confidence interval, 0.57-0.89), and mean corpuscular volume (hazard ratio 19.0, per log unit; 95% confidence interval, 4.79-75.0) were each independently associated with increased risk of death after resection of colorectal cancer liver metastasis (all P < .05). In turn, alkaline phosphatase, albumin, and mean corpuscular volume were combined to form a nontumor related prognostic score (2.942 × mean corpuscular volume + 0.399 × alkaline phosphatase-0.339 × albumin-12) × 10 (median, 16; range, 1-30). The nontumor related prognostic score had good-to-modest discriminatory ability in the external cohort (C-index = 0.58), which was comparable to the 3 established tumor-related prognostic scores (C-index: Fong clinical risk scores, 0.53, m-clinical risk scores, 0.55, GAME, 0.58). The addition of the nontumor related prognostic score to the tumor-related prognostic scores enhanced the discriminatory ability in the entire study cohort (C-index: nontumor related score+Fong, 0.60, nontumor related score+m-clinical risk scores, 0.61, nontumor related score+GAME, 0.64), as well reclassification improvement (42.5, 42.7%, and 21.2%, respectively)., Conclusion: Nontumor related prognostic information may help improve the prognostic stratification of patients after resection of colorectal cancer liver metastasis. The nontumor related prognostic score may be combined with tumor-related prognostic tools to enhance prognostic stratification of patients with colorectal cancer liver metastasis., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Assessing overall tumor burden on the basis of tumor number and size may assist in prognostic stratification of patients after resection of colorectal liver metastases (CRLM). We sought to define the prognostic accuracy of tumor burden by using machine learning (ML) algorithms compared with other commonly used prognostic scoring systems., Study Design: Patients who underwent hepatectomy for CRLM between 2001 and 2018 were identified from a multi-institutional database and split into training and validation cohorts. ML was used to define tumor burden (ML-TB) based on CRLM tumor number and size thresholds associated with 5-year overall survival. Prognostic ability of ML-TB was compared with the Fong and Genetic and Morphological Evaluation scores using Cohen's d., Results: Among 1,344 patients who underwent resection of CRLM, median tumor number (2, interquartile range 1 to 3) and size (3 cm, interquartile range 2.0 to 5.0) were comparable in the training (n = 672) vs validation (n = 672) cohorts; patient age (training 60.8 vs validation 61.0) and preoperative CEA (training 10.2 ng/mL vs validation 8.3 ng/mL) was also similar (p > 0.05). ML empirically derived optimal cutoff thresholds for number of lesions (3) and size of the largest lesion (1.3 cm) in the training cohort, which were then used to categorize patients in the validation cohort into 3 prognostic groups. Patients with low, average, or high ML-TB had markedly different 5-year overall survival (51.6%, 40.9%, and 23.1%, respectively; p < 0.001). ML-TB was more effective at stratifying patients relative to 5-year overall survival (low vs high ML-TB, d = 2.73) vs the Fong clinical (d = 1.61) or Genetic and Morphological Evaluation (d = 0.84) scores., Conclusions: Using a large international cohort, ML was able to stratify patients into 3 distinct prognostic categories based on overall tumor burden. ML-TB was noted to be superior to other CRLM prognostic scoring systems., (Copyright © 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Not all Americans may benefit equally from current improvements in breast and colorectal cancer screening and mortality rates., Methods: We performed a cross-sectional retrospective review of county-level screening, incidence, and mortality rates for breast and colon cancer utilizing three publicly available data sources from the Centers for Disease Control and Prevention (CDC), and their association with the Distressed Communities Index (DCI), a measure of local economic prosperity across communities., Results: After controlling for other factors, DCI was associated with county-level screening, incidence, and death rates per 100,000 for breast and colorectal cancer. There was an absolute increase of 0.77 (95% confidence interval [CI] 0.67-0.85, p < 0.001) in the proportion of women aged 40 years or older who had a screening mammogram for every 10-point decrease in DCI, which in turn correlated with an increase in the age-adjusted incidence by 1.68 per 100,000 (95% CI 1.37-2.00, p < 0.001). While the age-adjusted death rate for breast cancer was highest in the most distressed communities, the overall incidence of age-adjusted death decreased by 0.28 per 100,000 (95% CI -0.37 to -0.19, p < 0.001) with every 10-point decrease in DCI. For colorectal cancer, every 10-point decrease in DCI was similarly associated with an absolute 0.60 (95% CI 0.52-0.69, p < 0.001) increase in the proportion of individuals who had screening endoscopy. Increased colorectal screening in low-DCI counties was associated with a lower age-adjusted incidence rate (-0.80 per 100,000; 95% CI -0.94 to -0.65) and age-adjusted death rate (-0.55 per 100,000; 95% CI -0.62 to -0.49) of colorectal cancer per every 10-point decrease in DCI (p < 0.001)., Conclusion: The association of county-level socioeconomic and healthcare factors with breast and colorectal cancer outcomes was notable, with level of community distress impacting cancer screening, incidence, and mortality rates., (© 2021. Society of Surgical Oncology.)

Colorectal cancer (CRC) is one of the most common cancers in the world. The most important determinant of survival and prognosis is the stage and presence of metastasis. The liver is the most common location for CRC metastasis. The only curative treatment for CRC liver metastasis (CRLM) is resection; however, many patients are ineligible for surgical resection of CRLM. Locoregional treatments such as ablation and intra-arterial therapy are also available for patients with CRLM. Assessment of response after chemotherapy is challenging due to anatomical and functional changes. Antiangiogenic agents such as bevacizumab that are used in the treatment of CRLM may show atypical patterns of response on imaging. It is vital to distinguish patterns of response in addition to toxicities to various treatments. Imaging plays a critical role in evaluating the characteristics of CRLM and the approach to treatment. CT is the modality of choice in the diagnosis and management of CRLM. MRI is best used for indeterminate lesions and to assess response to intra-arterial therapy. PET-CT is often utilized to detect extrahepatic metastasis. State-of-the-art imaging is critical to characterize patterns of response to various treatments. We herein review the imaging characteristics of CRLM with an emphasis on imaging changes following the most common CRLM treatments., (© 2021. The Society for Surgery of the Alimentary Tract.)

Background: The objective of this study was to assess trends in the use as well as the outcomes of patients undergoing simultaneous versus staged resection for synchronous colorectal liver metastases., Methods: Patients undergoing resection for colorectal liver metastases between 2008 and 2018 were identified using a multi-institutional database. Trends in use and outcomes of simultaneous resection of colorectal liver metastases were examined over time and compared with that of staged resection after propensity score matching., Results: Among 1,116 patients undergoing resection for colorectal liver metastases, 690 (61.8%) patients had synchronous disease. Among them, 314 (45.5%) patients underwent simultaneous resection, while 376 (54.5%) had staged resection. The proportion of patients undergoing simultaneous resection for synchronous colorectal liver metastases increased over time (2008: 37.2% vs 2018: 47.4%; p tre nd  = 0.02). After propensity score matching (n = 201 per group), patients undergoing simultaneous resection for synchronous colorectal liver metastases had a higher incidence of overall (44.8% vs 34.3%; P = .03) and severe complications (Clavien-Dindo ≥III) (16.9% vs 7.0%; P = .002) yet comparable 90-day mortality (3.5% vs 1.0%; P = .09) compared with patients undergoing staged resection. The incidence of severe morbidity decreased over time (2008: 50% vs 2018: 11.1%; p tren d  = 0.02). Survival was comparable among patients undergoing simultaneous versus staged resection of colorectal liver metastases (3-year overall survival: 66.1% vs 62.3%; P = .67). Following simultaneous resection, severe morbidity and mortality increased incrementally based on the extent of liver resection and complexity of colectomy., Conclusion: While simultaneous resection was associated with increased morbidity, the incidence of severe morbidity decreased over time. Long-term survival was comparable after simultaneous resection versus staged resection of colorectal liver metastases., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The prognostic impact of colorectal liver metastasis (CRLM) morphologic characteristics relative to KRAS mutational status after hepatic resection remains ill defined., Study Design: Patients undergoing hepatectomy for CRLM between 2001 and 2018 were identified using an international multi-institutional database. Tumor burden score (TBS) was defined as distance from origin on a Cartesian plane that incorporated maximum tumor size (x-axis) and number of lesions (y-axis). Impact of TBS on overall survival (OS) relative to KRAS status (wild type [wtKRAS] vs mutated [mutKRAS]) was assessed., Results: Among 1,361 patients, the median number of metastatic lesions was 2 (interquartile range [IQR] 1-3), and median size of the largest metastatic lesion was 3.0 cm (IQR 2.0-5.0 cm), resulting in a median TBS of 4.1 (IQR 2.8-6.1); KRAS status was wtKRAS (n = 420, 30.9%), mutKRAS (n = 251, 18.4%), and unknown (n = 690, 50.7%). Overall median and 5-year OS were 49.5 months (95%CI 45.2-53.8) and 43.2%, respectively. In examining the entire cohort, TBS was associated with long-term prognosis (5-year OS, low TBS: 49.4% vs high TBS: 36.7%), as was KRAS mutational status (5-year OS, wtKRAS: 48.2% vs mutKRAS: 31.1%; unknown KRAS: 44.0%)(both p < 0.01). Among patients with wtKRAS tumors, TBS was strongly associated with improved OS (5-year OS, low TBS: 59.1% vs high TBS: 38.4%, p = 0.002); however, TBS failed to discriminate long-term prognosis among patients with mutKRAS tumors (5-year OS, low TBS: 37.4% vs high TBS: 26.7%, p = 0.19). In fact, patients with high TBS/wtKRAS CRLM had comparable outcomes to patients with low TBS/mutKRAS tumors (5-year OS, 38.4% vs 37.4%, respectively; p = 0.59). On multivariable analysis, while TBS was associated with OS among patients with wtKRAS CRLM (hazard ratio 1.43, 95%CI 1.02-2.00; p = 0.03), TBS was not an independent predictor of survival among patients with mutKRAS CRLM (HR 1.36, 95%CI 0.92-1.99; p = 0.12)., Conclusions: While TBS was associated with survival among patients with wtKRAS tumors, CRLM morphology was not predictive of long-term outcomes among patients with mutKRAS CRLM., (Copyright © 2020 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Two-stage hepatectomy (TSH) is an important tool in the management of bilateral colorectal liver metastases (CRLM). This study sought to examine the presentation, management, and outcomes of patients completing TSH in major hepatobiliary centers in the United States (US)., Methods: A retrospective review from five liver centers in the US identified patients who completed a TSH procedure for bilateral CRLM., Results: From December 2000 to March 2016, a total of 196 patients were identified. The majority of procedures were performed using an open technique (n = 194, 99.5%). The median number of tumors was 7 (range 2-33). One-hundred and twenty-eight (65.3%) patients underwent portal vein embolization. More patients received chemotherapy prior to the first stage than chemotherapy administration preceding the second stage (92% vs. 60%, p = 0.308). Median overall survival (OS) was 50 months, with a median follow-up of 28 months (range 2-143). Hepatic artery infusion chemotherapy was administered to 64 (32.7%) patients with similar OS as those managed without an infusion pump (p = 0.848). Postoperative morbidity following the second-stage resection was 47.4%. Chemotherapy prior to the second stage did not demonstrate an increased complication rate (p = 0.202). Readmission following the second stage was 10.3% and was associated with a decrease in disease-free survival (p = 0.003). OS was significantly decreased by positive resection margins and increased estimated blood loss (EBL; p = 0.036 and p = 0.05, respectively)., Conclusion: This is the largest TSH series in the US and demonstrates evidence of safety and feasibility in the management of bilateral CRLM. Outcomes are influenced by margin status and operative EBL.