A Prognostic Model To Predict Survival After Recurrence Among Patients With Recurrent Hepatocellular Carcinoma.

OBJECTIVE: We sought to develop and validate a preoperative model to predict survival after recurrence (SAR) in hepatocellular carcinoma (HCC). BACKGROUND: Although HCC is characterized by recurrence as high as 60%, models to predict outcomes after recurrence remain relatively unexplored. METHODS: Patients who developed recurrent HCC between 2000 and 2020 were identified from an international multi-institutional database. Clinicopathologic data on primary disease and laboratory and radiologic imaging data on recurrent disease were collected. Multivariable Cox regression analysis and internal bootstrap validation (5000 repetitions) were used to develop and validate the SARScore. Optimal Survival Tree analysis was used to characterize SAR among patients treated with various treatment modalities. RESULTS: Among 497 patients who developed recurrent HCC, median SAR was 41.2 months (95% CI 38.1-52.0). The presence of cirrhosis, number of primary tumors, primary macrovascular invasion, primary R1 resection margin, AFP>400 ng/mL on the diagnosis of recurrent disease, radiologic extrahepatic recurrence, radiologic size and number of recurrent lesions, radiologic recurrent bilobar disease, and early recurrence (≤24 months) were included in the model. The SARScore successfully stratified 1-, 3- and 5-year SAR and demonstrated strong discriminatory ability (3-year AUC: 0.75, 95% CI 0.70-0.79). While a subset of patients benefitted from resection/ablation, Optimal Survival Tree analysis revealed that patients with high SARScore disease had the worst outcomes (5-year AUC; training: 0.79 vs. testing: 0.71). The SARScore model was made available online for ease of use and clinical applicability ( https://yutaka-endo.shinyapps.io/SARScore/ ). CONCLUSION: The SARScore demonstrated strong discriminatory ability and may be a clinically useful tool to help stratify risk and guide treatment for patients with recurrent HCC.

Poor Access to Mental Healthcare is Associated with Worse Postoperative Outcomes Among Patients with Gastrointestinal Cancer.

BACKGROUND: Mental health has an important role in the care of cancer patients, and access to mental health services may be associated with improved outcomes. Thus, poor access to psychiatric services may contribute to suboptimal cancer treatment. We conducted a geospatial analysis to characterize psychiatrist distribution and assess the impact of mental healthcare shortages with surgical outcomes among patients with gastrointestinal cancer. METHODS: Medicare beneficiaries with mental illness diagnosed with complex gastrointestinal cancers between 2004 and 2016 were identified in the Surveillance, Epidemiology, and End Results (SEER)-Medicare registry. National Provider Identifier-registered psychiatrist locations were mapped and linked to SEER-Medicare records. Regional access to psychiatric services was assessed relative to textbook outcome, a composite assessment of postoperative complications, prolonged length of stay, 90-day readmission and mortality. RESULTS: Among 15,714 patients with mental illness and gastrointestinal cancer, 3937 were classified as having high access to psychiatric services while 3910 had low access. On multivariable logistic regression, areas with low access had higher risk of worse postoperative outcomes. Specifically, individuals residing in areas with low access had increased odds of prolonged length of stay (OR 1.11, 95%CI 1.01-1.22; p = 0.028) and 90-day readmission (OR 1.19, 95%CI 1.08-1.31; p < 0.001), as well as decreased odds of textbook outcome (OR 0.85, 95%CI 0.77-0.93; p < 0.001) and discharge to home (OR 0.89, 95%CI 0.80-0.99; p = 0.028). CONCLUSION: Patients with mental illness and lower access to psychiatric services had worse postoperative outcomes. Policymakers and providers should prioritize incorporating mental health screening and access to psychiatric services to address disparities among patients undergoing gastrointestinal surgery.

Association of Intellectual and Developmental Disabilities With Worse Outcomes After Surgical Treatment of Cancer.

BACKGROUND: Patients with intellectual and developmental disabilities (IDD) face unique challenges resulting in disparities in their health care. We sought to define the effect that IDD had on achievement of a "textbook outcome" (TO) following a cancer operation among a nationally representative cohort of patients. METHODS: Data on patients who underwent surgery for a malignant indication, including lung, breast, liver, biliary tract, pancreas, and colorectal, between 2014 and 2020 were extracted from the 100% Medicare Standard Analytical Files database. The association of IDD with TO (defined as the absence of postoperative complications, extended length of stay, 90-day readmission, and 90-day mortality), expenditures, and discharge status was assessed using multivariable logistic regression. RESULTS: Among 500,472 Medicare beneficiaries, 4,326 (0.9%) with IDD had a cancer diagnosis (breast, n=481; lung, n=419; hepatobiliary, n=194; pancreas, n=145; colorectal, n=3,087). Although overall incidence of TO was 50.5%, patients with IDD were less likely to achieve a TO than those without (37.1% vs 50.6%, respectively; odds ratio [OR], 0.50; 95% CI, 0.46-0.53; P<.001). On multivariable regression, patients with IDD had higher odds of a postoperative complication (OR, 1.53; 95% CI, 1.43-1.64), extended length of stay (OR, 2.06; 95% CI, 1.93-2.21), 90-day readmission (OR, 1.15; 95% CI, 1.07-1.24), 90-day mortality (OR, 1.90; 95% CI, 1.70-2.13), and discharge to a skilled nursing facility (OR, 4.28; 95% CI, 3.97-4.62) (all P<.001). CONCLUSIONS: Patients with IDD had a much lower chance of a postoperative TO, as well as discharge to a nonhome setting. The data highlight the need to improve the care of patients with IDD to assure equitable oncologic surgical care.

The Association of Food Insecurity and Surgical Outcomes Among Patients Undergoing Surgery for Colorectal Cancer.

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 ).

Association of Racial and Economic Privilege on Postoperative Outcomes Among Medicare Beneficiaries.

INTRODUCTION: Social determinants of health can play an important role in patient health. Privilege is a right, benefit, advantage, or opportunity that can positively affect all social determinants of health. We sought to assess variations in the prevalence of privilege among patient populations and define the association of privilege on postoperative surgical outcomes. METHODS: Medicare beneficiaries who underwent elective coronary artery bypass grafting, abdominal aortic aneurysm repair, total hip arthroplasty, total knee arthroplasty, colectomy, and lung resection were identified. The Index of Concentration of Extremes (ICE), a validated metric of both social spatial polarization and privilege was calculated and merged with county-level data obtained from the American Community Survey. Textbook outcome (TO) was defined as absence of postoperative complications, extended length of stay, 90-day mortality, and 90-day readmission. Multivariable regression analysis was performed to assess the relationship between ICE and TO. RESULTS: Among 1,885,889 Medicare beneficiaries who met inclusion criteria, 655,980 (34.8%) individuals resided in areas with the highest privilege (i.e., White, high-income homogeneity), whereas 221,314 (11.7%) individuals resided in areas of the lowest privilege (i.e., Black, low-income homogeneity). The overall incidence of TO was 66.2% (n = 1,247,558). On multivariable regression, residence in the most advantaged neighbourhoods was associated with a lower chance of surgical complications (odds ratio [OR] 0.90, 95% confidence interval [CI] 0.88-0.91), a prolonged length of stay (OR 0.81, 95% CI 0.79-82), 90-day readmission (OR 0.94, 95% CI 0.92-0.95), and 90-day mortality (OR 0.71, 95% CI 0.68-0.74) (all P < 0.001). Residence in the most privileged areas was associated with 19% increased odds of achieving TO (OR 1.19, 95% CI 1.18-1.21), as well as a 6% reduction in Medicare expenditures versus individuals in the least privileged counties (OR 0.94, 95% CI 0.94-0.94) (both P < 0.001). CONCLUSIONS: Privilege, based on the ICE joint measure of racial/ethnic and economic spatial concentration, was strongly associated with the likelihood to achieve an "optimal" TO following surgery. As healthcare is a basic human right, privilege should not be associated with disparities in surgical care.

Chemiluminescence of a Firefly Luciferin Analogue Reveals that Formation of the Key Intermediate Responsible for Excited State Generation Occurs on a Fully Concerted Step.

The chemiluminescence (CL) reaction of eight different 2-(4-hydroxyphenyl)-4,5-dihydrothiazole-4-carboxylate esters with an organic superbase and oxygen was investigated through a kinetic and computational study. These esters are all analogues to the luciferin substrate involved in efficient firefly bioluminescence. The kinetic data obtained from CL emission and light absorption assays were used in the context of linear free energy relationships (LFER); we obtained the Hammett reaction constant ρ = +1.62 ± 0.09 and the Brønsted constant ßlg = -0.39 ± 0.04. These observations from LFER, together with activation parameters obtained from Arrhenius plots, suggest that the formation of the high-energy intermediate (HEI) 1,2-dioxetanone occurs via a concerted mechanism during the rate-determining step of the reaction. Calculations performed using density functional theory support a late transition state for HEI formation within the reaction mechanism pathway, which was described considering geometric parameters, Wiberg bond indices from natural bond order analysis, and the atomic charges derived from the electrostatic potential.

Impact of Medicaid expansion on the multimodal treatment of biliary tract cancer.

INTRODUCTION: The impact of Medicaid expansion (ME) on the treatment of patients with cancer remains controversial, especially individuals requiring complex multidisciplinary care. We sought to evaluate the impact of Medicaid expansion (ME) on receipt of multimodal care, including surgical resection, for Stage I-III biliary tract cancer (BTC). METHODS: Patients diagnosed with BTC between 40 and 65 years of age were identified from the National Cancer Database and divided into pre- (2008-2012) and post- (2015-2018) ME cohorts. Difference-in-difference (DID) analysis was used to determine the impact of ME on the utilization of surgery and multimodal chemotherapy and/or radiotherapy treatment for BTC. RESULTS: Among 12,415 patients with BTC (extrahepatic, n = 5622, 45.3%; intrahepatic, n = 4352, 35.1%; gallbladder, n = 1944, 15.7%; overlapping, n = 497, 4.0%), 5835 (47.0%) and 6580 (53.0%) patients were diagnosed before versus after ME, respectively. Overall utilization of surgery (OR 1.13, 95% CI 1.02-1.26) and multimodality therapy (OR 1.13, 95% CI 1.01-1.27) increased in states that adopted ME. Utilization of surgery among uninsured/Medicaid patients in ME states increased relative to patients living in non-ME states (∆+10.1%, p = 0.01). Similarly, the use of multimodal treatment increased among uninsured/Medicaid patients living in ME versus non-ME states (∆+6.4%, p = 0.04); in contrast, there were no difference among patients with other insurance statuses (overall: ∆+1.5%, private: ∆-2.0%, other: ∆+3.9%, all p > 0.5). Uninsured/Medicaid patients with BTC who lived in a ME state had a lower risk of long-term death in the post-ME era (HR 0.81, 95% CI 0.67-0.98; p = 0.03). CONCLUSIONS: Implementation of ME positively impacted survival among patients who underwent surgical and multimodal treatment for Stage I-III BTC.

de Broglie-Bohm analysis of a nonlinear membrane: From quantum to classical chaos.

Within the de Broglie-Bohm theory, we numerically study a generic two-dimensional anharmonic oscillator including cubic and quartic interactions in addition to a bilinear coupling term. Our analysis of the quantum velocity fields and trajectories reveals the emergence of dynamical vortices. In their vicinity, fingerprints of chaotic behavior such as unpredictability and sensitivity to initial conditions are detected. The simultaneous presence of the off-diagonal -kxy and nonlinear terms leads to robust quantum chaos very analogous to its classical version.

Comparison of tumor response and outcomes of patients with hepatocellular carcinoma after multimodal treatment including immune checkpoint inhibitors - a systematic review and meta-analysis.

BACKGROUND: The efficacy of immune checkpoint inhibitors (ICIs) combined with tyrosine kinase inhibitors (TKIs), trans-arterial chemoembolization (TACE), and radiotherapy to treat hepatocellular carcinoma (HCC) has not been well-defined. We performed a meta-analysis to characterize tumor response and survival associated with multimodal treatment of HCC. METHODS: PubMed, Embase, Medline, Scopus, and CINAHL databases were searched (1990-2022). Random-effect meta-analysis was conducted to compare efficacy of treatment modalities. Odds ratios (OR) and standardized mean difference (SMD) were reported. RESULTS: Thirty studies (4170 patients) met inclusion criteria. Triple therapy regimen (ICI + TKI + TACE) had the highest overall disease control rate (DCR) (87%, 95% CI 83-91), while ICI + radiotherapy had the highest objective response rate (ORR) (72%, 95% CI 54%-89%). Triple therapy had a higher DCR than ICI + TACE (OR 4.49, 95% CI 2.09-9.63), ICI + TKI (OR 3.08, 95% CI 1.63-5.82), and TKI + TACE (OR 2.90, 95% CI 1.61-5.20). Triple therapy demonstrated improved overall survival versus ICI + TKI (SMD 0.72, 95% CI 0.37-1.07) and TKI + TACE (SMD 1.13, 95% CI 0.70-1.48) (both p < 0.05). Triple therapy had a greater incidence of adverse events (AEs) compared with ICI + TKI (OR 0.59, 95% CI 0.29-0.91; p = 0.02), but no difference in AEs versus ICI + TACE or TKI + TACE (both p > 0.05). CONCLUSION: The combination of ICIs, TKIs and TACE demonstrated superior tumor response and survival and should be considered for select patients with advanced HCC.

Persistence of Poverty and its Impact on Surgical Care and Postoperative Outcomes.

OBJECTIVE: We sought to characterize the association between prolonged county-level poverty with postoperative outcomes. BACKGROUND: The impact of long-standing poverty on surgical outcomes remains ill-defined. METHODS: Patients who underwent lung resection, colectomy, coronary artery bypass graft, or lower extremity joint replacement were identified from Medicare Standard Analytical Files Database (2015-2017) and merged with data from the American Community Survey and the United States Department of Agriculture. Patients were categorized according to the duration of high poverty status from 1980 to 2015 [ie, never high poverty (NHP), persistent poverty (PP)]. Logistic regression was used to characterize the association between the duration of poverty and postoperative outcomes. Principal component and generalized structural equation modeling were used to assess the effect of mediators in the achievement of Textbook Outcomes (TO). RESULTS: Overall, 335,595 patients underwent lung resection (10.1%), colectomy (29.4%), coronary artery bypass graft (36.4%), or lower extremity joint replacement (24.2%). While 80.3% of patients lived in NHP, 4.4% resided in PP counties. Compared with NHP, patients residing in PP were at increased risk of serious postoperative complications [odds ratio (OR)=1.10, 95% CI: 1.05-1.15], 30-day readmission (OR=1.09, 95% CI: 1.01-1.16), 30-day mortality (OR=1.08, 95% CI: 1.00-1.17), and higher expenditures (mean difference, $1010.0, 95% CI: 643.7-1376.4) (all P <0.05). Notably, PP was associated with lower odds of achieving TO (OR=0.93, 95% CI: 0.90-0.97, P <0.001); 65% of this effect was mediated by other social determinant factors. Minority patients were less likely to achieve TO (OR=0.81, 95% CI: 0.79-0.84, P <0.001), and the disparity persisted across all poverty categories. CONCLUSIONS: County-level poverty duration was associated with adverse postoperative outcomes and higher expenditures. These effects were mediated by various socioeconomic factors and were most pronounced among minority patients.

Impact of Community Privilege on Access to Care Among Patients Following Complex Cancer Surgery.

OBJECTIVE: We sought to define the impact of community privilege on variations in travel patterns and access to care at high-volume hospitals for complex surgical procedures. BACKGROUND: With increased emphasis on centralization of high-risk surgery, social determinants of health play a critical role in preventing equitable access to care. Privilege is a right, benefit, advantage, or opportunity that positively impacts all social determinants of health. METHODS: The California Office of State-wide Health Planning Database identified patients who underwent esophagectomy (ES), pneumonectomy (PN), pancreatectomy (PA), or proctectomy (PR) for a malignant diagnosis between 2012 and 2016 and was merged using ZIP codes with the Index of Concentration of Extremes, a validated metric of both spatial polarization and privilege obtained from the American Community Survey. Clustered multivariable regression was performed to assess the probability of undergoing care at a high-volume center, bypassing the nearest and high-volume center, and total real driving time and travel distance. RESULTS: Among 25,070 patients who underwent a complex oncologic operation (ES: n=1216, 4.9%; PN: n=13,247, 52.8%; PD: n=3559, 14.2%; PR: n=7048, 28.1%), 5019 (20.0%) individuals resided in areas with the highest privilege (i.e., White, high-income homogeneity), whereas 4994 (19.9%) individuals resided in areas of the lowest privilege (i.e., Black, low-income homogeneity). Median travel distance was 33.1 miles (interquartile range 14.4-72.2). Roughly, three-quarters of patients (overall: 74.8%, ES: 35.0%; PN: 74.3%; PD: 75.2%; PR: 82.2%) sought surgical care at a high-volume center. On multivariable regression, patients residing in the least advantaged communities were less likely to undergo surgery at a high-volume hospital (overall: odds ratio 0.65, 95% CI 0.52-0.81). Of note, individuals in the least privileged areas had longer travel distances (28.5 miles, 95% CI 21.2-35.8) to reach the destination facility, as well as over 70% greater odds of bypassing a high-volume hospital to undergo surgical care at a low-volume center (odds ratio 1.74, 95% CI 1.29-2.34) versus individuals living in the highest privileged areas. CONCLUSIONS AND RELEVANCE: Privilege had a marked effect on access to complex oncologic surgical care at high-volume centers. These data highlight the need to focus on privilege as a key social determinant of health that influences patient access to and utilization of health care resources.

The Impact of a Liver Transplant Program on the Outcomes of Hepatocellular Carcinoma.

OBJECTIVE: We sought to evaluate the impact of liver transplantation (LT) programs on the prognosis of hepatocellular carcinoma (HCC) patients who underwent liver resection (LR) and noncurative intent treatment. BACKGROUND: LT programs have an array of resources and services that would positively affect the prognosis of patients with HCC. METHODS: Patients who underwent LT, LR, radiotherapy (RT), or chemotherapy (CTx) for HCC between 2004 and 2018 were included in the National Cancer Database. Institutions with LT programs were defined as those that performed 1 or more LT for at least 5 years. Centers were stratified by hospital volume. The impact of LT programs was assessed after propensity score matching to achieve covariate balance. RESULTS: A total of 71,735 patients were identified, of which 7997 received LT (11.1%), 12,683 LR (17.7%), 15,675 RT (21.9%), and 35,380 CTx (49.3%). Among a total of 1267 distinct institutions, 94 (7.4%) were categorized as LT programs. Designation as an LT program was also associated with a high volume of LR and noncurative intent treatment (both P <0.001). After propensity score matching, LT programs were associated with better survival among LR and noncurative intent treatment patients. Although hospital volume was also associated with improved prognosis, LT programs were associated with additional survival benefits in noncurative intent treatment. On the other hand, no such benefit was noted in patients who underwent LR. CONCLUSIONS: The presence of an LT program was associated with a higher volume of LR and noncurative intent treatment. Furthermore, designation as an LT program had a "halo effect" on the prognosis of patients undergoing RT/CTx that went beyond the procedure-volume effect.

Predictors, Patterns, and Impact of Adequate Lymphadenectomy in Intrahepatic Cholangiocarcinoma.

INTRODUCTION: Despite lymph node metastases (LNMs) being associated with worse survival, adequate lymph node evaluation (LNE) has not been universally adopted for intrahepatic cholangiocarcinoma (ICC). We sought to evaluate trends in LNE, predictors of LNE and LNM, as well as the role of adequate lymphadenectomy in stratifying patients relative to survival. METHODS: Patients who underwent curative-intent liver resection for ICC (2010-2019) were identified from the National Cancer Database and stratified according to LNE: 0, 1-5 (inadequate lymphadenectomy) and ≥6 (adequate lymphadenectomy). Multivariate logistic regression was utilized to assess predictors of LNE and LNM. Overall survival and receipt of adequate lymphadenectomy were assessed relative to LNM and log-odds of lymph nodes (LODDS). RESULTS: Among 6507 patients, adequate lymphadenectomy was performed in only 1118 (17.2%) patients, although compliance with adequate lymphadenectomy increased over time (2010-2012: 14.2% vs. 2016-2019: 18.9%; p < 0.001). After controlling for relevant factors, region (reference: Northeast; Midwest: odds ratio [OR] 1.90, 95% confidence interval [CI] 1.48-2.44; South: OR 1.64, 95% CI 1.28-2.10; West: OR 1.83, 95% CI 1.37-2.44) and preoperative nodal status (reference: cN0; cNx: OR 2.18, 95% CI 1.68-2.95; cN1: OR 3.88, 95% CI 3.02-4.98) strongly predicted adequate lymphadenectomy. Furthermore, adequate lymphadenectomy resulted in higher odds of detecting ≥1 LNMs (OR 2.63, 95% CI 2.25-3.08), regardless of preoperative nodal status. Adequate lymphadenectomy demonstrated an improved ability to stratify patients relative to 5-year survival based on LNM (N0: 51.3% vs. N1: 30.6% vs. N2: 13.7%; p < 0.001) and LODDS (LODDS1: 50.7% vs. LODDS2: 27.4% vs. LODDS3: 15.7%; p < 0.001). CONCLUSIONS: Compliance with adequate lymphadenectomy at the time of surgery for ICC remains suboptimal with marked regional variations. Adequate lymphadenectomy was associated with higher odds of detecting LNM and improved survival stratification relative to both LNM and LODDS. Greater emphasis on nodal evaluation is required to ensure optimal management of ICC.

Impact of Staging Concordance and Downstaging After Neoadjuvant Therapy on Survival Following Resection of Intrahepatic Cholangiocarcinoma: A Bayesian Analysis.

INTRODUCTION: Concordance between clinical and pathological staging, as well as the overall survival (OS) benefit associated with neoadjuvant therapy (NAT) remain ill-defined. We sought to determine the impact of staging accuracy and NAT downstaging on OS among patients with intrahepatic cholangiocarcinoma (ICC). METHODS: Patients treated for ICC between 2010 and 2018 were identified using the National Cancer Database. A Bayesian approach was applied to estimate NAT downstaging. OS was assessed relative to staging concordant/overstaged disease treated with upfront surgery, understaged disease treated with upfront surgery, no downstaging, and downstaging after NAT. RESULTS: Among 3384 patients, 2904 (85.8%) underwent upfront surgery, whereas 480 (14.2%) received NAT and 85/480 (18.4%) were downstaged. Patients with cT3 (odds ratio [OR] 2.12, 95% confidence interval [CI] 1.34-3.34), cN1 (OR 2.47, 95% CI 1.71-3.58) disease, and patients treated at high-volume facilities (OR 1.63, 95% CI 1.13-2.36) were more likely to receive NAT (all p < 0.05). Median OS was 40.1 months (95% CI 38.6-43.4). Patients with cT1-2N1 (NAT: 31.5 months vs. upfront surgery: 22.4 months; p = 0.04) and cT3-4N1 (NAT: 27.8 months vs. upfront surgery: 14.4 months; p = 0.01) disease benefited most from NAT. NAT downstaging decreased the risk of death among patients with cT3-4N1 disease (hazard ratio [HR] 0.35, 95% CI 0.15-0.82). In contrast, understaged patients with cT1-2N0/X (HR 2.15, 95% CI 1.83-2.53) and cT3-4N0/X (HR 1.71, 95% CI 1.06-2.74) disease treated with upfront surgery had increased risk of death. CONCLUSIONS: Patients with N1 ICC treated with NAT demonstrated improved OS compared with upfront surgery. Downstaging secondary to NAT conferred survival benefits among patients with cT3-4N1 versus upfront surgery. NAT should be considered in ICC patients with advanced T disease and/or nodal metastases.

Association of Minority-Serving Hospital Status with Post-Discharge Care Utilization and Expenditures in Gastrointestinal Cancer.

BACKGROUND: Disparities in utilization of post-discharge care and overall expenditures may relate to site of care and race/ethnicity. We sought to define the impact of minority-serving hospitals (MSHs) on postoperative outcomes, discharge disposition, and overall expenditures associated with an episode of surgical care. METHODS: Patients who underwent resection for esophageal, colon, rectal, pancreatic, and liver cancer were identified from Medicare Standard Analytic Files (2013-2017). A MSH was defined as the top decile of facilities treating minority patients (Black and/or Hispanic). The impact of MSH on outcomes of interest was analyzed using multivariable logistic regression and generalized linear regression models. Textbook outcome (TO) was defined as no postoperative complications, no prolonged length of stay, and no 90-day mortality or readmission. RESULTS: Among 113,263 patients, only a small subset of patients underwent surgery at MSHs (n = 4404, 3.9%). While 52.3% of patients achieved TO, rates were lower at MSHs (MSH: 47.2% vs. non-MSH: 52.5%; p < 0.001). On multivariable analysis, receiving care at an MSH was associated with not achieving TO (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.76-0.87) and concomitantly higher odds of additional post-discharge care (OR 1.10, 95% CI 1.01-1.20). Patients treated at an MSH also had higher median post-discharge expenditures (MSH: $8400, interquartile range [IQR] $2300-$22,100 vs. non-MSH: $7000, IQR $2200-$17,900; p = 0.002). In fact, MSHs remained associated with a 11.05% (9.78-12.33%) increase in index expenditures and a 16.68% (11.44-22.17%) increase in post-discharge expenditures. CONCLUSIONS: Patients undergoing surgery at a MSH were less likely to achieve a TO. Additionally, MSH status was associated with a higher likelihood of requiring post-discharge care and higher expenditures.

The Impact of Medicaid Expansion on Early-Stage Pancreatic Adenocarcinoma at High- Versus Low-Volume Facilities.

INTRODUCTION: While Medicaid Expansion (ME) has improved healthcare access, disparities in outcomes after volume-dependent surgical care persist. We sought to characterize the impact of ME on postoperative outcomes among patients undergoing resection for pancreatic ductal adenocarcinoma (PDAC) at high-volume (HVF) versus low-volume (LVF) facilities. METHODS: Patients who underwent resection for PDAC were identified from the National Cancer Database (NCDB; 2011-2018). HVF was defined as ≥20 resections/year. Patients were divided into pre- and post-ME cohorts, and the primary outcome was textbook oncologic outcomes (TOO). Difference-in-difference (DID) analysis was used to assess changes in TOO achievement among patients living in ME versus non-ME states. RESULTS: Among 33,764 patients who underwent resection of PDAC, 19.1% (n = 6461) were treated at HVF. Rates of TOO achievement were higher at HVF (HVF: 45.7% vs. LVF: 32.8%; p < 0.001). On multivariable analysis, undergoing surgery at HVF was associated with higher odds of achieving TOO (odds ratio [OR] 1.60, 95% confidence interval [CI] 1.49-1.72) and improved overall survival (OS) [hazard ratio (HR) 0.96, 95% CI 0.92-0.99]. Compared with patients living in non-ME states, individuals living in ME states were more likely to achieve TOO on adjusted DID analysis (5.4%, p = 0.041). Although rates of TOO achievement did not improve after ME at HVF (3.7%, p = 0.574), ME contributed to markedly higher rates of TOO among patients treated at LVF (6.7%, p = 0.022). CONCLUSIONS: Although outcomes for PDAC remain volume-dependent, ME has contributed to significant improvement in TOO achievement among patients treated at LVF. These data highlight the impact of ME on reducing disparities in surgical outcomes relative to site of care.

The Impact of Medicaid Expansion on Early-Stage Hepatocellular Carcinoma Care.

INTRODUCTION: The impact of Medicaid expansion (ME) on hepatocellular carcinoma (HCC) remains controversial, and heterogeneous effects on care processes may relate to sociodemographic factors. We sought to evaluate the association between ME and receipt of surgery in early-stage HCC. METHODS: Patients diagnosed with early-stage HCC between 40 and 64 years of age were identified from the National Cancer Database and divided into pre- (2004-2012) and post- (2015-2017) expansion cohorts. Logistic regression was used to identify predictors of surgical treatment. Difference-in-difference (DID) analysis assessed changes in surgical treatment between patients living in ME and non-ME states. RESULTS: Among 19,745 patients, 12,220 (61.9%) were diagnosed before ME and 7525 (38.1%) after. Although overall utilization of surgery decreased after expansion (ME, pre-expansion: 62.2% versus post-expansion: 51.6%; non-ME, pre-expansion: 62.1% versus post-expansion: 50.8%, p < 0.001), this trend varied relative to insurance status. Notably, receipt of surgery increased among uninsured/Medicaid patients living in ME states after expansion (pre-expansion: 48.1%, post-expansion: 52.3%, p < 0.001). Moreover, treatment at academic or high-volume facilities increased the likelihood of undergoing surgery before expansion. After expansion, treatment at an academic facility and living in an ME state (OR 1.28, 95% CI 1.07-1.54, p < 0.01) were predictors of surgical treatment. DID analysis demonstrated increased utilization of surgery for uninsured/Medicaid patients living in ME states relative to non-ME states (uninsured/Medicaid: 6.4%, p < 0.05), although no differences were noted among patients with other insurance statuses (overall: 0.7%, private: -2.0%, other: 0.3%, all p > 0.05). CONCLUSIONS: Implementation of ME heterogeneously impacted utilization of care in early-stage HCC. Notably, uninsured/Medicaid patients residing in ME states demonstrated increased utilization of surgical treatment after expansion.

Circulating Tumor DNA, Imaging, and Carcinoembryonic Antigen: Comparison of Surveillance Strategies Among Patients Who Underwent Resection of Colorectal Cancer-A Systematic Review and Meta-analysis.

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.

Racial Segregation Among Patients with Cholangiocarcinoma-Impact on Diagnosis, Treatment, and Outcomes.

BACKGROUND: Racial segregation, an effect of historical marginalization, may impact cancer care and outcomes. We sought to examine the impact of racial segregation on the diagnosis, treatment, and outcomes of patients with cholangiocarcinoma (CCA). PATIENTS AND METHODS: Data on Black and White patients with CCA were obtained from the linked SEER-Medicare database (2004-2015) and 2010 Census data. The index of dissimilarity (IoD), a validated measure of segregation, was used to assess Black-White disparities in stage disease presentation, surgery for localized disease, and cancer-specific mortality. Multivariable Poisson regression was performed, and competing risk regression analysis was used to determine cancer-specific survival. RESULTS: Among 7480 patients with CCA, 90.2% (n = 6748) were White and 9.8% (n = 732) were Black. Overall, Black patients were more likely to reside in segregated areas compared with White patients (IoD, 0.42 vs. 0.38; p < 0.05). On multivariable Poisson regression, Black patients were more likely to present with advanced-stage disease [relative risk (RR) 1.17, 95% confidence interval (CI) 1.08-1.27; p < 0.001] and were less likely to undergo surgery for localized disease (RR 0.62, 95% CI 0.51-0.76; p < 0.001). Black patients also had worse cancer-specific survival (CSS) compared with White patients (median CSS: 4 vs. 8 months; p < 0.01). Black patients living in the highest areas of segregation had 40% increased hazard of mortality versus White patients residing in the lowest IoD areas (hazard ratio 1.40, 95% CI 1.10-1.80; p < 0.01). CONCLUSION: Racial segregation, as a proxy for structural racism, had a marked effect on Black-White disparities among patients with CCA.

Disparities in Socioeconomic Factors Mediate the Impact of Racial Segregation Among Patients With Hepatopancreaticobiliary Cancer.

BACKGROUND: Structural racism within the U.S. health care system contributes to disparities in oncologic care. This study sought to examine the socioeconomic factors that underlie the impact of racial segregation on hepatopancreaticobiliary (HPB) cancer inequities. METHODS: Both Black and White patients who presented with HPB cancer were identified from the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database (2005-2015) and 2010 Census data. The Index of Dissimilarity (IoD), a validated measure of segregation, was examined relative to cancer stage at diagnosis, surgical resection, and overall mortality. Principal component analysis and structural equation modeling were used to determine the mediating effect of socioeconomic factors. RESULTS: Among 39,063 patients, 86.4 % (n = 33,749) were White and 13.6 % (n = 5314) were Black. Black patients were more likely to reside in segregated areas than White patients (IoD, 0.62 vs. 0.52; p < 0.05). Black patients in highly segregated areas were less likely to present with early-stage disease (relative risk [RR], 0.89; 95 % confidence interval [CI] 0.82-0.95) or undergo surgery for localized disease (RR, 0.81; 95% CI 0.70-0.91), and had greater mortality hazards (hazard ratio 1.12, 95% CI 1.06-1.17) than White patients in low segregation areas (all p < 0.05). Mediation analysis identified poverty, lack of insurance, education level, crowded living conditions, commute time, and supportive income as contributing to 25 % of the disparities in early-stage presentation. Average income, house price, and income mobility explained 17 % of the disparities in surgical resection. Notably, average income, house price, and income mobility mediated 59 % of the effect that racial segregation had on long-term survival. CONCLUSION: Racial segregation, mediated through underlying socioeconomic factors, accounted for marked disparities in access to surgical care and outcomes for patients with HPB cancer.