RFWD3 modulates response to platinum chemotherapy and promotes cancer associated phenotypes in high grade serous ovarian cancer.

Background: DNA damage repair is frequently dysregulated in high grade serous ovarian cancer (HGSOC), which can lead to changes in chemosensitivity and other phenotypic differences in tumours. RFWD3, a key component of multiple DNA repair and maintenance pathways, was investigated to characterise its impact in HGSOC. Methods: RFWD3 expression and association with clinical features was assessed using in silico analysis in the TCGA HGSOC dataset, and in a further cohort of HGSOC tumours stained for RFWD3 using immunohistochemistry. RFWD3 expression was modulated in cell lines using siRNA and CRISPR/cas9 gene editing, and cells were characterised using cytotoxicity and proliferation assays, flow cytometry, and live cell microscopy. Results: Expression of RFWD3 RNA and protein varied in HGSOCs. In cell lines, reduction of RFWD3 expression led to increased sensitivity to interstrand crosslinking (ICL) inducing agents mitomycin C and carboplatin. RFWD3 also demonstrated further functionality outside its role in DNA damage repair, with RFWD3 deficient cells displaying cell cycle dysregulation, reduced cellular proliferation and reduced migration. In tumours, low RFWD3 expression was associated with increased tumour mutational burden, and complete response to platinum chemotherapy. Conclusion: RFWD3 expression varies in HGSOCs, which can lead to functional effects at both the cellular and tumour levels.

High throughput screening identifies dasatinib as synergistic with trametinib in low grade serous ovarian carcinoma.

BACKGROUND: Low grade serous ovarian carcinoma (LGSOC) is a distinct histotype of ovarian cancer characterised high levels of intrinsic chemoresistance, highlighting the urgent need for new treatments. High throughput screening in clinically-informative cell-based models represents an attractive strategy for identifying candidate treatment options for prioritisation in clinical studies. METHODS: We performed a high throughput drug screen of 1610 agents across a panel of 6 LGSOC cell lines (3 RAS/RAF-mutant, 3 RAS/RAF-wildtype) to identify novel candidate therapeutic approaches. Validation comprised dose-response analysis across 9 LGSOC models and 5 high grade serous comparator lines. RESULTS: 16 hits of 1610 screened compounds were prioritised for validation based on >50% reduction in nuclei counts in over half of screened cell lines at 1000 nM concentration. 11 compounds passed validation, and the four agents of greatest interest (dasatinib, tyrosine kinase inhibitor; disulfiram, aldehyde dehydrogenase inhibitor; carfilzomib, proteasome inhibitor; romidepsin, histone deacetylase inhibitor) underwent synergy profiling with the recently approved MEK inhibitor trametinib. Disulfiram demonstrated excellent selectivity for LGSOC versus high grade serous ovarian carcinoma comparator lines (P = 0.003 for IC50 comparison), while the tyrosine kinase inhibitor dasatinib demonstrated favourable synergy with trametinib across multiple LGSOC models (maximum zero interaction potency synergy score 46.9). The novel, highly selective Src family kinase (SFK) inhibitor NXP900 demonstrated a similar trametinib synergy profile to dasatinib, suggesting that SFK inhibition is the likely driver of synergy. CONCLUSION: Dasatinib and other SFK inhibitors represent novel candidate treatments for LGSOC and demonstrate synergy with trametinib. Disulfiram represents an additional treatment strategy worthy of investigation.

Deficiencies in germline genetic testing in young-onset colorectal cancer patients.

BACKGROUND: Young-onset colorectal cancer (YO-CRC) patients have high rates of pathologic genetic variants on germline testing, however it is unclear what factors are associated with genetic testing completion. METHODS: We performed a retrospective review of YO-CRC patients aged ≤50 years between 2014 and 2021 who received the entirety of their cancer care at a single institution. The primary outcome was completion of germline multigene panel testing. Variables were examined for association with germline multigene panel testing. RESULTS: Among 100 YO-CRC patients, only 31 â€‹% (n â€‹= â€‹31) completed genetic testing. Testing rates did not differ by colorectal cancer stage but were significantly higher among patients who received chemotherapy (39.8 â€‹% vs 5.9 â€‹%; p â€‹= â€‹0.01) and in patients with increasing number of relatives with a family history of cancer (p â€‹< â€‹0.01). CONCLUSIONS: Only one-third of YO-CRC patients completed genetic testing. Patients seen by oncology or with increasingly strong family cancer history were more likely to complete genetic testing.

Can screen-time help? An analysis of usage of patient engagement technology following colorectal surgery.

BACKGROUND: Patient engagement technologies (PETs) guide patients through the perioperative period. We aimed to investigate the levels of patient engagement with PETs through the peri-operative period and its impact on clinical outcomes. METHODS: Retrospective cohort study of patients undergoing elective colorectal surgery from 2018 to 2022. Outcomes were length of stay, readmissions, and complications within 30 days of index hospitalization. RESULTS: 359 (89.1%) patients activated the PET. Patients completed a median of 7 surveys, 2 in-hospital health-checks, and 1 post-discharge health-check. Median LOS was 3 days, 57 (14.1%) patients were readmitted, and 56 (13.9%) had a complication. Patients who completed no surveys had longer LOS than those who completed 2 or more. Patients who were readmitted and had post-operative complications completed significantly fewer surveys and post-discharge health-checks. Completion of surveys in more phases was associated with shorter LOS and lower readmission rates. Completion of more post-discharge health-checks was associated with lower complication rate. CONCLUSIONS: The use of PETs improves patient outcomes and experiences in the perioperative period. Patients who engage more frequently with PETs have shorter LOS with lower readmission and post-operative complication rates.

Understanding the Impact of Enhanced Recovery Programs on Social Vulnerability, Race, and Colorectal Surgery Outcomes.

BACKGROUND: Increasing social vulnerability, measured by the Social Vulnerability Index, has been associated with worse surgical outcomes. However, less is known about the impact of social vulnerability on patients who underwent colorectal surgery under enhanced recovery programs. OBJECTIVE: We hypothesized that increasing social vulnerability is associated with worse outcomes before enhanced recovery implementation, but that after implementation, disparities in outcomes would be reduced. DESIGN: Retrospective cohort study using multivariable logistic regression to identify associations of social vulnerability and enhanced recovery with outcomes. SETTINGS: Institutional American College of Surgeons National Surgical Quality Improvement Program database. PATIENTS: Patients undergoing elective colorectal surgery (2010-2020). Enhanced recovery programs were implemented in 2015. Those adhering to 70% or more of enhanced recovery program components were defined as enhanced recovery and all others as nonenhanced recovery. OUTCOMES: Length of stay, complications, and readmissions. RESULTS: Of 1523 patients, 589 (38.7%) were in the enhanced recovery group, with 625 patients (41%) in the lowest third of the Social Vulnerability Index, 411 (27%) in the highest third. There were no differences in Social Vulnerability Index distribution by the enhanced recovery group. On multivariable modeling, social vulnerability was not associated with increased length of stay, complications, or readmissions in the enhanced recovery group. Black race was associated with increased length of stay in both the nonenhanced recovery (OR 1.2; 95% CI, 1.1-1.3) and enhanced recovery groups (OR 1.2; 95% CI, 1.1-1.4). Enhanced recovery adherence was associated with reductions in racial disparities in complications as the Black race was associated with increased odds of complications in the nonenhanced recovery group (OR 1.9; 95% CI, 1.2-3.0) but not in the enhanced recovery group (OR 0.8; 95% CI, 0.4-1.6). LIMITATIONS: Details of potential factors affecting enhanced recovery program adherence were not assessed and are the subject of current work by this team. CONCLUSION: High social vulnerability was not associated with worse outcomes among both enhanced recovery and nonenhanced recovery colorectal patients. Enhanced recovery program adherence was associated with reductions in racial disparities in complication rates. However, disparities in length of stay remain, and work is needed to understand the underlying mechanisms driving these disparities. See Video Abstract . COMPRENDIENDO EL IMPACTO DE LOS PROGRAMAS DE RECUPERACIN MEJORADA EN LA VULNERABILIDAD SOCIAL, LA RAZA Y LOS RESULTADOS DE LA CIRUGA COLORRECTAL: ANTECEDENTES:El aumento de la vulnerabilidad social medida por el índice de vulnerabilidad social se ha asociado con peores resultados quirúrgicos. Sin embargo, se sabe menos sobre el impacto de la vulnerabilidad social en los pacientes de cirugía colorrectal bajo programas de recuperación mejorados.OBJETIVO:Planteamos la hipótesis de que el aumento de la vulnerabilidad social se asocia con peores resultados antes de la implementación de la recuperación mejorada, pero después de la implementación, las disparidades en los resultados se reducirían.DISEÑO:Estudio de cohorte retrospectivo que utilizó regresión logística multivariable para identificar asociaciones de vulnerabilidad social y recuperación mejorada con los resultados.ESCENARIO:Base de datos institucional del Programa de Mejora Nacional de la Calidad de la Cirugía del American College of Surgeons.PACIENTES:Pacientes sometidos a cirugía colorrectal electiva (2010-2020). Programas de recuperación mejorada implementados en 2015. Aquellos que se adhieren a ≥70% de los componentes del programa de recuperación mejorada definidos como recuperación mejorada y todos los demás como recuperación no mejorada.MEDIDAS DE RESULTADO:Duración de la estancia hospitalaria, complicaciones y reingresos.RESULTADOS:De 1.523 pacientes, 589 (38,7%) estaban en el grupo de recuperación mejorada, con 732 (40,3%) pacientes en el tercio más bajo del índice de vulnerabilidad social, 498 (27,4%) en el tercio más alto, y no hubo diferencias en la distribución del índice vulnerabilidad social por grupo de recuperación mejorada. En el modelo multivariable, la vulnerabilidad social no se asoció con una mayor duración de la estancia hospitalaria, complicaciones o reingresos en ninguno de los grupos de recuperación mejorada. La raza negra se asoció con una mayor duración de la estadía tanto en el grupo de recuperación no mejorada (OR1,2, IC95% 1,1-1,3) como en el grupo de recuperación mejorada (OR1,2, IC95% 1,1-1,4). La adherencia a la recuperación mejorada se asoció con reducciones en las disparidades raciales en las complicaciones, ya que la raza negra se asoció con mayores probabilidades de complicaciones en el grupo de recuperación no mejorada (OR1,9, IC95% 1,2-3,0), pero no en el grupo de recuperación mejorada (OR0,8, IC95% 0,4-1,6).LIMITACIONES:No se evaluaron los detalles de los factores potenciales que afectan la adherencia al programa de recuperación mejorada y son el tema del trabajo actual de este equipo.CONCLUSIÓN:La alta vulnerabilidad social no se asoció con peores resultados entre los pacientes colorrectales con recuperación mejorada y sin recuperación mejorada. Una mayor adherencia al programa de recuperación se asoció con reducciones en las disparidades raciales en las tasas de complicaciones. Sin embargo, persisten disparidades en la duración de la estadía y es necesario trabajar para comprender los mecanismos subyacentes que impulsan estas disparidades. (Traducción-Dr. Felipe Bellolio ).

Development of a comprehensive survey to assess key socioecological determinants of health.

BACKGROUND: Although disparities in surgical outcomes are well-documented, our understanding of how socioecological factors drive these disparities remains limited. Comprehensive and efficient assessment tools are needed. This study's objective was to develop and assess the acceptability and feasibility of a comprehensive tool evaluating socioecological determinants of health in patients requiring colorectal surgery. METHODS: In the first phase, a comprehensive socioecological determinant of health assessment tool was developed. A review of validated socioecological health evaluation instruments was conducted, and a 2-step modified Delphi method addressed the length, clarity, appropriateness, and redundancy of each instrument. A comprehensive tool was then finalized. In the second phase, the tool was tested for acceptability and feasibility in adult patients requiring colorectal surgery using a theory-guided framework at 3 Alabama hospitals. Relationships between survey responses and measures of acceptability and feasibility were evaluated using results from initial pilot tests of the survey. RESULTS: In Phase 1, a modified Delphi process led to the development of a comprehensive tool that included 31 socioecological determinants of health (88 questions). Results of acceptability and feasibility were globally positive (>65%) for all domains. Overall, 83% of participants agreed that others would have no trouble completing the survey, 90.4% of respondents reported the survey was not burdensome, 97.6% of patients reported having enough time to complete the survey, and 80.9% agreed the survey was well-integrated into their appointment. CONCLUSION: An 88-item assessment tool measuring 31 socioecological determinants of health was developed with high acceptability and feasibility for patients who required colorectal surgery. This work aids in the development of research needed to understand and address surgical disparities.

Compartment-specific multiomic profiling identifies SRC and GNAS as candidate drivers of epithelial-to-mesenchymal transition in ovarian carcinosarcoma.

BACKGROUND: Ovarian carcinosarcoma (OCS) is an exceptionally aggressive and understudied ovarian cancer type harbouring distinct carcinomatous and sarcomatous compartments. Here, we seek to identify shared and compartment-specific events that may represent potential therapeutic targets and candidate drivers of sarcomatous compartment formation through epithelial-to-mesenchymal transition (EMT). METHODS: We performed multiomic profiling (exome sequencing, RNA-sequencing, microRNA profiling) of paired carcinomatous and sarcomatous components in 12 OCS cases. RESULTS: While paired sarcomatous and carcinomatous compartments demonstrate substantial genomic similarities, multiple loci are recurrently copy number-altered between components; regions containing GNAS and SRC are recurrently gained within the sarcomatous compartment. CCNE1 gain is a common event in OCS, occurring more frequently than in high grade serous ovarian carcinoma (HGSOC). Transcriptomic analysis suggests increased MAPK activity and subtype switching toward poor prognosis HGSOC-derived transcriptomic subtypes within the sarcomatous component. The two compartments show global differences in microRNA profiles, with differentially expressed microRNAs targeting EMT-related genes (SIRT1, ZEB2) and regulators of pro-tumourigenic pathways (TGFß, NOTCH); chrX is a highly enriched target of these microRNAs and is also frequently deleted across samples. The sarcomatous component harbours significantly fewer CD8-positive cells, suggesting poorer immune engagement. CONCLUSION: CCNE1 gain and chrX loss are frequent in OCS. SRC gain, increased GNAS expression and microRNA dysregulation represent potential mechanisms driving sarcomatous compartment formation.

Distinct histopathological features are associated with molecular subtypes and outcome in low grade serous ovarian carcinoma.

Low grade serous ovarian carcinoma (LGSOC) demonstrates unique clinical and molecular features compared to other ovarian cancer types. The relationship between common histological features of LGSOC and molecular events, such as hormone receptor expression patterns and MAPK gene mutation status, remains poorly understood. Recent data suggest some of these molecular features may be biomarkers of response to recently introduced biologically-targeted therapies, namely endocrine therapy and MEK inhibitors. We utilize a cohort of 63 pathologically-confirmed LGSOC cases with whole exome sequencing and hormone receptor expression data to investigate these relationships. LGSOC cases demonstrated uniformly high oestrogen receptor (ER) expression, but variable progesterone receptor (PR) expression intensity. 60% and 37% of cases demonstrated micropapillary and macropapillary patterns of stromal invasion, respectively. 63% of cases demonstrated desmoplasia, which was significantly associated with advanced disease stage and visible residual disease after cytoreductive surgery. MAPK-mutant cases (KRAS, BRAF, NRAS) more frequently demonstrated macropapillary stromal invasion, while Chr1p loss was associated with desmoplasia and low PR expression. Presence of micropapillary stromal invasion and low PR expression were associated with significantly poorer survival after accounting for stage and residual disease status. Together, these data identify novel relationships between histopathological features and molecularly-defined subgroups in LGSOC.

Racial Differences in Aging-Related Deficits Among Older Adults With Colorectal Cancer.

BACKGROUND: Despite the known influences of both race- and aging-related factors in colorectal cancer outcomes and mortality, limited literature is available on the intersection between race and aging-related impairments. OBJECTIVE: To explore racial differences in frailty and geriatric deficit subdomains among patients with colorectal cancer. DESIGN: Retrospective study using data from the Cancer and Aging Resilience Evaluation registry. SETTINGS: A comprehensive cancer center in the Deep South. PATIENTS: Older adults (aged ≥60 years) with colorectal cancer. MAIN OUTCOME MEASURES: Measure of frailty and geriatric assessment subdomains of physical function, functional status, cognitive complaints, psychological function, and health-related quality of life. RESULTS: Black patients lived in areas with a higher social vulnerability index compared to White patients (0.69 vs 0.49; p < 0.01) and had limited social support more often (54.5% vs 34.9%; p = 0.01). After adjustment for age, cancer stage, comorbidities, and social vulnerability index, Black patients were found to have a higher rate of frailty than White patients (adjusted OR 3.77; 95% CI, 1.76-8.18; p = 0.01). In addition, Black patients had more physical limitations (walking 1 block: adjusted OR 1.93; 95% CI, 1.02-3.69; p = 0.04), functional limitations (activities of daily living: adjusted OR 3.21; 95% CI, 1.42-7.24; p = 0.01), and deficits in health-related quality of life (poor global self-reported health: adjusted OR 2.45; 95% CI, 1.23-5.13; p = 0.01). Similar findings were shown after stratification by stage I to III vs IV. LIMITATIONS: Retrospective study at a single institution. CONCLUSIONS: Among older patients with colorectal cancer, Black patients were more likely to be frail than White patients, with deficits observed specifically in physical function, functional status, and health-related quality of life. Geriatric assessment may provide an important tool in addressing racial inequities in colorectal cancer. DIFERENCIAS RACIALES EN LOS DFICITS RELACIONADOS CON EL ENVEJECIMIENTO ENTRE ADULTOS MAYORES CON CNCER COLORRECTAL: ANTECEDENTES: A pesar de las influencias conocidas de los factores relacionados con la raza y el envejecimiento en los resultados y la mortalidad del cáncer colorectal, hay muy poca literatura sobre la intersección entre los impedimentos relacionados con la raza y el envejecimiento.OBJETIVO: El objetivo era explorar las diferencias raciales en los subdominios de fragilidad y déficit geriátrico entre los pacientes con cáncer colorectal.DISEÑO: Estudio retrospectivo utilizando datos del registro Cancer and Aging Resilience Evaluation.AJUSTES: Un centro oncológico integral en el Sur Profundo.PACIENTES: Adultos mayores (≥60 años) con cáncer colorrectal de raza Negra o Blanca.PRINCIPALES MEDIDAS DE RESULTADO: Medida compuesta de fragilidad y subdominios de evaluación geriátrica de función física, estado funcional, quejas cognitivas, función psicológica y calidad de vida relacionada con la salud.RESULTADOS: De los 304 pacientes incluidos, el 21,7% (n = 66) eran negros y la edad media era de 69 años. Los pacientes negros vivían en áreas con un índice de vulnerabilidad social (SVI) más alto en comparación con los pacientes blancos (SVI 0,69 vs 0,49; p < 0,01) y con mayor frecuencia tenían apoyo social limitado (54,5% vs 34,9%; p = 0,01). Después de ajustar por edad, estadio del cáncer, comorbilidades y SVI, los pacientes de raza negra tenían una mayor tasa de fragilidad en comparación con los pacientes de raza blanca (ORa 3,77, IC del 95%: 1,76-8,18; p = 0,01). Además, los pacientes negros tenían más limitaciones físicas (caminar 1 cuadra: ORa 1,93, IC 95% 1,02-3,69; p = 0,04), limitaciones funcionales (actividades de la vida diaria: ORa 3,21, IC 95% 1,42-7,24; p = 0,01 ) y déficits en la calidad de vida relacionada con la salud (mala salud global autoinformada: ORa 2,45, IC 95% 1,23-5,13; p = 0,01). Las quejas cognitivas y las funciones psicológicas no difirieron según la raza (p > 0,05). Se mostraron hallazgos similares después de la estratificación por estadio I-III frente a IV.LIMITACIONES: Estudio retrospectivo en una sola institución.CONCLUSIONES: Entre los pacientes mayores con cáncer colorrectal, los pacientes negros tenían más probabilidades que los pacientes blancos de ser frágiles, observándose déficits específicamente en la función física, el estado funcional y la calidad de vida relacionada con la salud. La evaluación geriátrica puede proporcionar una herramienta importante para abordar las desigualdades raciales en el cáncer colorrectal.

Whole exome sequencing of low grade serous ovarian carcinoma identifies genomic events associated with clinical outcome.

OBJECTIVES: Low-grade serous ovarian carcinoma (LGSOC) is a distinct, rare, ovarian cancer type characterised by younger patient age and intrinsic chemoresistance. Understanding the molecular landscape is crucial for optimising targeted therapy. METHODS: Genomic data from whole exome sequencing of tumour tissue was analysed in a LGSOC cohort with detailed clinical annotation. RESULTS: 63 cases were analysed and three subgroups identified based on single nucleotide variants: canonical MAPK mutant (cMAPKm: 52%, KRAS/BRAF/NRAS), MAPK-associated gene mutation (MAPK-assoc: 27%) and MAPK wild-type (MAPKwt: 21%). NOTCH pathway disruption occurred across all subgroups. Tumour mutational burden (TMB), mutational signatures and recurrent copy number (CN) changes varied across the cohort with co-occurrence of chromosome 1p loss and 1q gain (CN Chr1pq) a recurrent feature. Low TMB and CN Chr1pq were associated with inferior disease-specific survival (HR 6.43; p < 0.001 and HR 3.29, p = 0.011 respectively). Stepwise genomic classification in relation to outcome resulted in four groups (TMB low; CN Chr1pq; MAPKwt/MAPKassoc; cMAPKm). 5 year disease-specific survival was 46%, 55%, 79% and 100% respectively for these groups. The two most favourable genomic subgroups were enriched for the SBS10b mutational signature, particularly the cMAPKm subgroup. CONCLUSIONS: LGSOC comprises multiple genomic subgroups with distinct clinical and molecular features. Chr1pq CN arm disruption and TMB represent promising methods to identify individuals with poorer prognosis. Further investigation of the molecular basis for these observations is required. MAPKwt cases represent around a fifth of patients. NOTCH inhibitors represent a candidate therapeutic strategy worthy of exploration across these cases.

The association of social vulnerability with colorectal enhanced recovery program failure.

Background: Enhanced recovery programs (ERPs) improve outcomes, but over 20 % of patients fail ERP and the contribution of social vulnerability is unknown. This study aimed to characterize the association between social vulnerability and ERP adherence and failure. Methods: This was a retrospective cohort study of colorectal surgery patients between 2015 and 2020 utilizing ACS-NSQIP data. Patients who failed ERP (LOS > 6 days) were compared to patients not failing ERP. The CDC's social vulnerability index (SVI) was used to assess social vulnerability. Result: 273 of 1191 patients (22.9 %) failed ERP. SVI was a significant predictor of ERP failure (OR 4.6, 95 % CI 1.3-16.8) among those with >70 % ERP component adherence. SVI scores were significantly higher among patients non-adherent with 3 key ERP components: preoperative block (0.58 vs. 0.51, p < 0.01), early diet (0.57 vs. 0.52, p = 0.04) and early foley removal (0.55 vs. 0.50, p < 0.01). Conclusions: Higher social vulnerability was associated with non-adherence to 3 key ERP components as well as ERP failure among those who were adherent with >70 % of ERP components. Social vulnerability needs to be recognized, addressed, and included in efforts to further improve ERPs. Key message: Social vulnerability is associated with non-adherence to enhanced recovery components and ERP failure among those with high ERP adherence. Social vulnerability needs to be addressed in efforts to improve ERPs.

Racial disparities in postoperative outcomes persist for patients with inflammatory bowel disease under a colorectal enhanced recovery program.

INTRODUCTION: Enhanced recovery programs (ERPs) reduce racial disparities in surgical outcomes for general colorectal surgery populations. It is unclear, however, if disparities in IBD populations are impacted by ERPs. METHODS: Retrospective study comparing IBD patients undergoing major elective colorectal operations before (2006-2014) and after (2015-2021) ERP implementation using ACS-NSQIP data. The primary outcome of length of stay (LOS) was analyzed by negative binomial regression, and secondary outcomes (complications and readmissions) by logistic regression. RESULTS: Of 466 IBD patients, 47% were pre-ERP and 53% were ERP patients. In multivariable analysis stratified by ERP period, Black race was associated with increased odds of complications in the pre-ERP (OR 3.6, 95%CI 1.4-9.3) and ERP groups (OR 3.1 95%CI 1.3-7.6). Race was not a predictor of LOS or readmission in either group. High social vulnerability was associated with increased odds of readmission pre-ERP (OR 15.1, 95%CI 2.1-136.3), but this disparity was mitigated under ERPs (OR 1.4, 95%CI 0.4-5.6). CONCLUSION: While ERPs mitigated some disparities by social vulnerability, racial disparities persist in IBD populations even under ERPs. Further work is needed to achieve surgical equity for IBD patients.

A socioecological qualitative analysis of barriers to care in colorectal surgery.

BACKGROUND: Although specific social determinants of health have been associated with disparities in surgical outcomes, there exists a gap in knowledge regarding the mechanisms of these associations. Gaining perspectives from multiple socioecological levels can help elucidate these mechanisms. Our study aims to identify social determinants of health that act as barriers or facilitators to surgical care among colorectal surgery stakeholders. METHODS: We recruited participants representing 5 socioecological levels: patients (individual); caregivers/surgeons (interpersonal); and leaders in hospitals (organizational), communities (community), and government (policy). Patients participated in focus groups, and the remaining participants underwent individual interviews. Semistructured interview guides were used to explore barriers and facilitators to surgical care at each socioecological level. Transcripts were analyzed by 3 coders in an inductive thematic approach with content analyses. The intercoder agreement was 93%. RESULTS: Six patient focus groups (total n = 18) and 12 key stakeholder interviews were conducted. The mean age of patients was 54.7 years, 66% were Black, and 61% were female. The most common diseases were colorectal cancer (28%), inflammatory bowel disease (28%), and diverticulitis (22%). Key social determinants of health impacting surgical care emerged at each level: individual (clear communication, mental stress), interpersonal (provider communication and trust, COVID-related visitation restrictions), organizational (multiple forms of contact, quality educational materials, scheduling systems, discrimination), community (community and family support and transportation), and policy (charity care, patient advocacy organizations, insurance coverage). CONCLUSION: Key social determinants of health-impacting care among colorectal surgery patients emerged at each socioecological level and may provide targets for interventions to reduce surgical disparities.

Disparities in Perioperative Use of Patient Engagement Technologies - Not All Use is Equal.

OBJECTIVE: To determine the association of patient-level characteristics on the use of a patient engagement technology during the perioperative period. SUMMARY OF BACKGROUND DATA: As implementation of patient engagement technologies continues to grow, it remains unclear who uses, and not uses, these technologies. Existing literature suggests significant disparities in usage of other technologies by patient age, race, sex, and geographic location, however, have yet to characterize patient usage of patient engagement technologies. METHODS: This is a retrospective cohort study of patients undergoing elective surgery by a colorectal surgeon between January 2018 and March 2020 who enrolled in a patient engagement technology at a single institution. Patients enrolled received educational content, healthcare reminders, patient reported outcome (PRO) surveys, and health checks preoperatively, in-hospital, and for 30-days postdischarge. The primary outcome was patient activation of the patient engagement technology. Secondary outcomes were completion of at least 1 PRO survey, 1 in-hospital health check, and 1 postdischarge health check. RESULTS: Of 549 patients who enrolled in the patient engagement technology, 473 (86.2%) activated. On multivariable stepwise regression, female patients [odds ratio (OR) 2.4, confidence interval (CI) 1.4-4.0, P = 0.001] and privately insured patients (OR 2.0, CI 1.1-3.8, P = 0.03) were more likely to activate. Black patients were less likely to activate (OR 0.5, CI 0.3-0.9, P = 0.02). Once activated, privately insured patients were more likely to complete PRO surveys (OR 2.3, CI 1.2-4.3, P = 0.01), in-hospital health checks (OR 2.4, CI 1.4-4.1, P = 0.002), and postdischarge health checks (OR 1.9, CI 1.1 -3.3, P < 0.001) than uninsured patients. Black patients were less likely to complete PRO surveys (OR 0.4, CI 0.3-0.7, P = 0.001) and in-hospital health checks (OR 0.6, CI 0.4-0.9, P = 0.03) than White patients. CONCLUSIONS: Use of a patient engagement technology in the perioperative period differs significantly by sex, race/ethnicity, and insurance status. These technologies may not be used equally by all patients, which should be considered during implementation of interventions to improve surgical outcomes.

Molecular characteristics and clinical behaviour of epithelial ovarian cancers.

Ovarian carcinoma (OC) is an umbrella term for multiple distinct diseases (histotypes), each with their own developmental origins, clinical behaviour and molecular profile. Accordingly, OC management is progressing away from a one-size-fits all approach, toward more molecularly-driven, histotype-specific management strategies. Our knowledge of driver events in high grade serous OC, the most common histotype, has led to major advances in treatments, including PARP inhibitor use. However, these agents are not suitable for all patients, most notably for many of those with rare OC histotypes. Identification of additional targeted therapeutic strategies will require a detailed understanding of the molecular landscape in each OC histotype. Until recently, tumour profiling studies in rare histotypes were sparse; however, significant advances have been made over the last decade. In particular, reports of genomic characterisation in endometrioid, clear cell, mucinous and low grade serous OC have significantly expanded our understanding of mutational events in these tumour types. Nonetheless, substantial knowledge gaps remain. This review summarises our current understanding of each histotype, highlighting recent advances in these unique diseases and outlining immediate research priorities for accelerating progress toward improving patient outcomes.

The University of Alabama at Birmingham Surgery Community Network: Tackling the Challenges of Rural Surgery.

Over the past 5 years, The University of Alabama at Birmingham (UAB) Department of Surgery has taken a keen interest in the practice of surgery in rural Alabama and has established the UAB surgery community network. Our goal is to improve the delivery of surgical care in rural areas through active recruitment of rural surgeons, the development of research around rural surgery practice, and the expansion of a surgery network throughout the state. Here, we will present the challenges faced by rural surgery, our early work to address these challenges, and offer a plan for moving forward.

Healthcare utilization trajectory among survivors of colorectal cancer.

PURPOSE: To examine healthcare utilization patterns among patients < 65 y with colorectal cancer (CRC) from pre-diagnosis to 3 y into survivorship. METHODS: Truven Health Analytics MarketScan Commercial Claims and Encounters Database was used to identify patients diagnosed with non-metastatic CRC between 2014 and 2016, with follow-up until 12/31/2019. Total visits (inpatient and outpatient) were estimated for 6 months intervals from 2 y to 1 months prior to CRC diagnosis (pre-cancer phase) and from a 1-y post-cancer diagnosis to a 3-y post-cancer diagnosis (survivorship phase). Utilization patterns from pre- to post-diagnosis were defined using median and 75th percentile visit counts. Interrupted time series (ITS) analyses examined pre- and post-cancer diagnosis utilization trends. Multivariable regression models estimated pre-cancer factors associated with high and low utilization patterns. RESULTS: Median age at CRC was 54 y (21-62); 50.6% of the patients were male, 30.9% were diagnosed with rectal cancer. ITS analyses demonstrated four utilization patterns with distinct pre- and post-cancer diagnosis utilization trends. Rectal cancer (RR = 1.13, p < 0.001) and high pre-cancer utilization (RR = 2.05, p < 0.001) were associated with a greater risk of high survivor phase utilization. Gastrointestinal conditions accounted for the greatest proportion of visits in pre-cancer phase (18%) and survivorship (17%), followed by cardiovascular disease (10% and 8%). CONCLUSIONS: Distinct patterns of healthcare utilization are observed both in the pre-cancer phase and survivorship phase of colorectal cancer and are influenced by cancer location, age, therapeutic exposures, and prior healthcare needs. IMPLICATIONS FOR CANCER SURVIVORS: Not all patients will require the same level or type of long-term follow-up. Identifying indication-specific healthcare utilization patterns that provide evidence for risk stratification may facilitate a more patient-centric and economically sustainable way to deliver care.