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.

Benchmarks in Liver Resection for Intrahepatic Cholangiocarcinoma.

INTRODUCTION: Benchmarking in surgery has been proposed as a means to compare results across institutions to establish best practices. We sought to define benchmark values for hepatectomy for intrahepatic cholangiocarcinoma (ICC) across an international population. METHODS: Patients who underwent liver resection for ICC between 1990 and 2020 were identified from an international database, including 14 Eastern and Western institutions. Patients operated on at high-volume centers who had no preoperative jaundice, ASA class <3, body mass index <35 km/m2, without need for bile duct or vascular resection were chosen as the benchmark group. RESULTS: Among 1193 patients who underwent curative-intent hepatectomy for ICC, 600 (50.3%) were included in the benchmark group. Among benchmark patients, median age was 58.0 years (interquartile range [IQR] 49.0-67.0), only 28 (4.7%) patients received neoadjuvant therapy, and most patients had a minor resection (n = 499, 83.2%). Benchmark values included ≥3 lymph nodes retrieved when lymphadenectomy was performed, blood loss ≤600 mL, perioperative blood transfusion rate ≤42.9%, and operative time ≤339 min. The postoperative benchmark values included TOO achievement ≥59.3%, positive resection margin ≤27.5%, 30-day readmission ≤3.6%, Clavien-Dindo III or more complications ≤14.3%, and 90-day mortality ≤4.8%, as well as hospital stay ≤14 days. CONCLUSIONS: Benchmark cutoffs targeting short-term perioperative outcomes can help to facilitate comparisons across hospitals performing liver resection for ICC, assess inter-institutional variation, and identify the highest-performing centers to improve surgical and oncologic outcomes.

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 ).

The Relevance of Radial Margin Status in Perihilar Cholangiocarcinoma: A State-of-the-Art Narrative Review.

BACKGROUND: Prognosis of perihilar cholangiocarcinoma (PHCC) is poor, and curative-intent resection is the most effective treatment associated with long-term survival. Surgery is technically demanding since it involves a major hepatectomy with en bloc resection of the caudate lobe and extrahepatic bile duct. Furthermore, to achieve negative margins, it may be necessary to perform concomitant vascular resection or pancreatoduodenectomy. Despite this aggressive approach, recurrence is often observed, considering 5-year recurrence-free survival below 15% and 5-year overall survival that barely exceeds 40%. SUMMARY: The literature reports that survival rates are better in patients with negative margins, and surprisingly, R0 resections range between 19% and 95%. This variability is probably due to different surgical strategies and the pathologist's expertise with specimens. In fact, a proper pathological examination of residual disease should take into consideration both the ductal and the radial margin (RM) status. Currently, detailed pathological reports are lacking, and there is a likelihood of misinterpreting residual disease status due to the missing of RM description and the utilization of various definitions for surgical margins. KEY MESSAGES: The aim of PHCC surgery is to achieve negative margins including RM. More clarity in reporting on RM is needed to define true radical resection and consistent design of oncological studies for adjuvant treatments.

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.

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.

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.

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.

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.

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.

Disparities in NCCN Guideline-Compliant Care for Patients with Early-Stage Pancreatic Adenocarcinoma at Minority-Serving versus Non-Minority-Serving Hospitals.

BACKGROUND: Racial/ethnic disparities in pancreatic adenocarcinoma (PDAC) outcomes may relate to receipt of National Comprehensive Cancer Network (NCCN) guideline-compliant care. We assessed the association between treatment at minority-serving hospitals (MSH) and receipt of NCCN-compliant care. PATIENTS AND METHODS: Patients who underwent resection of early-stage PDAC between 2006 and 2019 were identified from the National Cancer Database (NCDB). MSH was defined as the top decile of facilities treating minority ethnicities (Black and/or Hispanic). Factors associated with receipt of NCCN-compliant care and its impact on overall survival (OS) were assessed. RESULTS: Among 44,873 patients who underwent resection of PDAC, most were treated at non-MSH (n = 42,571, 94.9%), while a smaller subset were treated at MSH (n = 2302, 5.1%). Patients treated at MSH were more likely to be at a younger median age (MSH 66 years versus non-MSH 67 years), Black or Hispanic (MSH 58.4% versus non-MSH 12.0%), and not insured (MSH 7.8% versus non-MSH 1.6%). While 71.7% (n = 31,182) of patients were compliant with NCCN care, guideline-compliant care was lower at MSH (MSH 62.5% versus non-MSH 72.2%). On multivariable analysis, receiving care at MSH was associated with not receiving guideline-compliant care [odds ratio (OR) 0.63, 95% confidence interval (CI) 0.53-0.74]. At non-MSH, non-white patients had lower odds of receiving guideline-compliant PDCA care (OR 0.85, 95% CI 0.78-0.91). Failure to comply was associated with worse overall survival (OS) [hazard ratio (HR) 1.50, 95% CI 1.46-1.54, all p < 0.001]. CONCLUSIONS: Patients with PDAC treated at MSH and minorities treated at non-MSH were less likely to receive NCCN-compliant care. Failure to comply with guideline-based PDAC treatment was associated with worse OS.

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.

Higher Tumor Burden Status Dictates the Impact of Surgical Margin Status on Overall Survival in Patients Undergoing Resection of Intrahepatic Cholangiocarcinoma.

BACKGROUND: The present study aimed to examine the prognostic significance of margin status following hepatectomy of intrahepatic cholangiocarcinoma (ICC) relative to overall tumor burden and nodal status. METHOD: Patients who underwent curative-intent surgery for ICC between 1990 and 2017 were included from a multi-institutional database. The impact of margin status and width on overall survival (OS) was examined relative to TBS and preoperative nodal status. RESULTS: Among 1105 patients with ICC who underwent resection, median tumor burden score (TBS) was 6.1 (IQR 4.2-8.8) and 218 (19.7%) patients had N1 disease. More than one in eight patients had an R1 surgical margin (n = 154, 13.9%). Among patients with low or medium TBS, an increasing margin width was associated with an incrementally improved 5-year OS (R1 31.9% vs. 1-3 mm 38.5% vs. 3-10 mm 48.0% vs. ≥ 10 mm 52.3%). In contrast, among patients with a high TBS, margin width was not associated with better survival (R1 28.9% vs. 1-3 mm 22.8% vs. 3-10 mm 29.6% vs. ≥ 10 mm 13.7%). In addition, surgical margin status did not impact survival with cutoffs of TBS 7 or greater. Furthermore, patients with low or medium TBS and preoperative negative lymph nodes derived a survival benefit from an R0 resection (R1 resection, HR 2.15, 95% CI 1.35-3.44, p = 0.001). In contrast, margin status was not associated with prognosis among patients with a high TBS and preoperative positive/suspicious lymph nodes (R1 resection, HR 1.34, 95% CI 0.58-3.11, p = 0.50). CONCLUSION: R0 resection and wider margin resection resulted in improved outcomes in patients with low tumor burden; however, the survival benefit of negative margin status disappeared in patients with underlying poor tumor biology.

Long-Term Recurrence-Free and Overall Survival Differ Based on Common, Proliferative, and Inflammatory Subtypes After Resection of Intrahepatic Cholangiocarcinoma.

INTRODUCTION: While generally associated with poor prognosis, intrahepatic cholangiocarcinoma (ICC) can have a heterogeneous presentation and natural history. We sought to identify specific ICC subtypes that may be associated with varied long-term outcomes and patterns of recurrence after liver resection. METHODS: Patients who underwent curative-intent resection for ICC from 2000 to 2020 were identified from a multi-institutional database. Hierarchical cluster analysis characterized three ICC subtypes based on morphology (i.e., tumor burden score [TBS]) and biology (i.e., preoperative neutrophil-to-lymphocyte ratio [NLR] and CA19-9 levels). RESULTS: Among 598 patients, the cluster analysis identified three ICC subtypes: Common (n = 300, 50.2%) (median, TBS: 4.5; NLR: 2.4; CA19-9: 38.0 U/mL); Proliferative (n = 246, 41.1%) (median, TBS: 8.8; NLR: 2.9; CA19-9: 71.2 U/mL); Inflammatory (n = 52, 8.7%) (median, TBS: 5.4; NLR: 12.6; CA19-9: 26.7 U/mL). Median overall survival (OS) (Common: 72.0 months; Proliferative: 31.4 months; Inflammatory: 22.9 months) and recurrence-free survival (RFS) (Common: 21.5 months; Proliferative: 11.9 months; Inflammatory: 9.0 months) varied considerably among the different ICC subtypes (all p < 0.001). Even though patients with Inflammatory ICC had more favorable T-(T1/T2, Common: 84.4%; Proliferative: 80.6%; Inflammatory: 86.5%) and N-(N0, Common: 14.0%; Proliferative: 20.7%; Inflammatory: 26.9%) disease, the Inflammatory subtype was associated with a higher incidence of intra- and extrahepatic recurrence (Common: 15.8%; Proliferative: 24.2%; Inflammatory: 28.6%) (all p = 0.01). CONCLUSIONS: Cluster analysis identified three distinct subtypes of ICC based on TBS, NLR, and CA19-9. ICC subtype was associated with RFS and OS and predicted worse outcomes among patients. Despite more favorable T- and N-disease, the Inflammatory ICC subtype was associated with worse outcomes ICC subtype should be considered in the prognostic stratification of patients.

A Novel Online Calculator to Predict Risk of Microvascular Invasion in the Preoperative Setting for Hepatocellular Carcinoma Patients Undergoing Curative-Intent Surgery.

BACKGROUND: The presence of microvascular invasion (MVI) has been highlighted as an important determinant of hepatocellular carcinoma (HCC) prognosis. We sought to build and validate a novel model to predict MVI in the preoperative setting. METHODS: Patients who underwent curative-intent surgery for HCC between 2000 and 2020 were identified using a multi-institutional database. Preoperative predictive models for MVI were built, validated, and used to develop a web-based calculator. RESULTS: Among 689 patients, MVI was observed in 323 patients (46.9%). On multivariate analysis in the test cohort, preoperative parameters associated with MVI included α-fetoprotein (AFP; odds ratio [OR] 1.50, 95% confidence interval [CI] 1.23-1.83), imaging tumor burden score (TBS; hazard ratio [HR] 1.11, 95% CI 1.04-1.18), and neutrophil-to-lymphocyte ratio (NLR; OR 1.18, 95% CI 1.03-1.35). An online calculator to predict MVI was developed based on the weighted ß-coefficients of these three variables ( https://yutaka-endo.shinyapps.io/MVIrisk/ ). The c-index of the test and validation cohorts was 0.71 and 0.72, respectively. Patients with a high risk of MVI had worse disease-free survival (DFS) and overall survival (OS) compared with low-risk MVI patients (3-year DFS: 33.0% vs. 51.9%, p < 0.001; 5-year OS: 44.2% vs. 64.8%, p < 0.001). DFS was worse among patients who underwent an R1 versus R0 resection among those patients at high risk of MVI (R0 vs. R1 resection: 3-year DFS, 36.3% vs. 16.1%, p = 0.002). In contrast, DFS was comparable among patients at low risk of MVI regardless of margin status (R0 vs. R1 resection: 3-year DFS, 52.9% vs. 47.3%, p = 0.16). CONCLUSION: Preoperative assessment of MVI using the online tool demonstrated very good accuracy to predict MVI.