Postoperative morbidity after simultaneous versus staged resection of synchronous colorectal liver metastases: Impact of hepatic tumor burden.

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

Liver transplantation access and outcomes: Impact of variations in liver-specific specialty care.

BACKGROUND: We sought to characterize the impact access to gastroenterologists/hepatologists has on liver transplantation listing, as well as time on the liver transplantation waitlist and post-transplant outcomes. METHODS: Liver transplantation registrants aged >18 years between January 1, 2004 and December 31, 2019 were identified from the Scientific Registry of Transplant Recipients Standard Analytic Files. The liver transplantation registration ratio was defined as the ratio of liver transplant waitlist registrations in a given county per 1,000 liver-related deaths. RESULTS: A total of 150,679 liver transplantation registrants were included. Access to liver transplantation centers and liver-specific specialty physicians varied markedly throughout the United States. Of note, the liver transplantation registration ratio was lower in counties with poor access to liver-specific care versus counties with adequate access (poor access 137.2, interquartile range 117.8-163.2 vs adequate access 157.6, interquartile range 127.3-192.2, P < .001). Among patients referred for liver transplantation, the cumulative incidence of waitlist mortality and post-transplant graft survival was comparable among patients with poor versus adequate access to liver-specific care (both P > .05). Among liver transplantation recipients living in areas with poor access, after controlling for recipient and donor characteristics, cold ischemic time, and model for end-stage liver disease score, the area deprivation index predicted graft survival (referent, low area deprivation index; medium area deprivation index, hazard ratio 1.52, 95% confidence interval 1.03-12.23; high area deprivation index, 1.45, 95% confidence interval 1.01-12.09, both P < .05). CONCLUSION: Poor access to liver-specific care was associated with a reduction in liver transplantation registration, and individuals residing in counties with high social deprivation had worse graft survival among patients living in counties with poor access to liver-specific care.

Optimal policy tree to assist in adjuvant therapy decision-making after resection of colorectal liver metastases.

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

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.

Liver transplantation for elderly patients with early-stage hepatocellular carcinoma.

BACKGROUND: Although liver resection is a viable option for patients with early-stage hepatocellular carcinoma (HCC), liver transplantation is the optimal treatment. The aim of this study was to identify characteristics of liver transplantation for elderly patients, and to assess the therapeutic benefit derived from liver transplantation over liver resection. METHODS: This was a population-based study of patients undergoing liver transplantation for HCC in the USA between 2004 and 2018. Data were retrieved from the National Cancer Database. Elderly patients were defined as individuals aged 70 years and over. Propensity score overlap weighting was used to control for heterogeneity between the liver resection and liver transplantation cohorts. RESULTS: Among 4909 liver transplant recipients, 215 patients (4.1 per cent) were classified as elderly. Among 5922 patients who underwent liver resection, 1907 (32.2 per cent) were elderly. Elderly patients who underwent liver transplantation did not have a higher hazard of dying during the first 5 years after transplantation than non-elderly recipients. After propensity score weighting, liver transplantation was associated with a lower risk of death than liver resection. Other factors associated with overall survival included diagnosis during 2016-2018, non-white/non-African American race, and α-fetoprotein level over 20 ng/dl. CONCLUSION: Elderly patients with HCC should not be excluded from liver transplantation based on age only. Transplantation leads to favourable survival compared with liver resection.

Modified integrated tumor burden, liver function, systemic inflammation, and tumor biology score to predict long-term outcomes after resection for hepatocellular carcinoma.

BACKGROUND: A preoperative predictive score for hepatocellular carcinoma (HCC) can help stratify patients who undergo resection relative to long-term outcomes and tailor treatment strategies. METHODS: Patients who underwent curative-intent hepatectomy for HCC between 2000 and 2020 were identified from an international multi-institutional database. A risk score (mFIBA) was developed using an Eastern cohort and then validated using a Western cohort. RESULTS: Among 957 patients, 443 and 514 patients were included from the Eastern and Western cohorts, respectively. On multivariable analysis, alpha-feto protein (HR1.97, 95%CI 1.42-2.72), neutrophil-to-lymphocyte ratio (HR1.74, 95%CI 1.28-2.38), albumin-bilirubin grade (HR1.66, 95%CI 1.21-2.28), and imaging tumor burden score (HR1.25, 95%CI 1.12-1.40) were associated with OS. The c-index in the Eastern test and Western validation cohorts were 0.69 and 0.67, respectively. Notably, mFIBA score outperformed previous HCC staging systems. 5-year OS incrementally decreased with an increase in mFIBA. On multivariable Cox regression analysis, the mFIBA score was associated with worse OS (HR1.18, 95%CI 1.13-1.23) and higher risk of recurrence (HR1.16, 95%CI 1.11-1.20). An easy-to-use calculator of the mFIBA score was made available online (https://yutaka-endo.shinyapps.io/mFIBA_score/). DISCUSSION: The online mFIBA calculator may help surgeons with clinical decision-making to individualize perioperative treatment strategies for patients undergoing resection of 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.

Association between the Environmental Quality Index and Textbook Outcomes Among Medicare Beneficiaries Undergoing Surgery for Early-Stage Pancreatic Adenocarcinoma.

BACKGROUND: Access to high-quality cancer care is affected by environmental exposures and structural inequities. This study sought to investigate the association between the environmental quality index (EQI) and achievement of textbook outcomes (TO) among Medicare beneficiaries over the age of 65 who underwent surgical resection for early-stage pancreatic adenocarcinoma (PDAC). METHODS: Patients diagnosed with early-stage PDAC from 2004 to 2015 were identified using the SEER-Medicare database and combined with the US Environmental Protection Agency's EQI data. High EQI category indicated poor environmental quality, whereas low EQI indicated better environmental conditions. RESULTS: A total of 5,310 patients were included, of which 45.0% (n = 2,387) patients achieved TO. Median age was 73 years and more than half were female (n = 2,807, 52.9%), married (n = 3,280, 61.8%), and resided in the Western region of the US (n = 2,712, 51.1%). On multivariable analysis, patients residing in moderate and high EQI counties were less likely to achieve a TO (referent: low EQI; moderate EQI: OR 0.66, 95% CI 0.46-0.95; high EQI: OR 0.65, 95% CI 0.45-0.94; p < 0.05). Increasing age (OR 0.98, 95%CI 0.97-0.99), racial minorities (OR 0.73, 95% CI 0.63-0.85), having a Charlson co-morbidity index > 2 (OR 0.54, 95%CI 0.47-0.61) and stage II disease (OR 0.82, 95%CI 0.71-0.96) were also associated with not achieving a TO (all p < 0.001). CONCLUSION: Older Medicare patients residing in moderate or high EQI counties were less likely to achieve an "optimal" TO after surgery. These results demonstrate that environmental factors may drive post-operative outcomes among patients with PDAC.

The impact of recurrence timing and tumor burden score on overall survival among patients undergoing repeat hepatectomy for colorectal liver metastases.

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

Travel distance and social vulnerability index: Impact on liver-related mortality among patients with end-stage liver disease.

INTRODUCTION: The reasons for the geographic disparities in liver-related mortality across the US remain ill-defined. We sought to investigate the impact of travel distance to liver transplantation (LT) programs and social vulnerability on county differences in liver-related mortality. METHODS: Data on LT registrants were obtained from the Scientific Registry of Transplant Recipients Standard Analytic Files (SRTR SAFs) between 2004 and 2019. Liver-related mortality data were obtained from the Center for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) platform. Spatial epidemiological clustering of county-level LT registration and liver-related mortality rates was determined using local Moran's I. Comparison analyses assessed social vulnerability index (SVI) and travel distance within various county clusters. RESULTS: Among 151 864 LT waitlist registrants who were diagnosed with liver disease due to hepatitis C virus (HCV) or hepatitis B virus (HBV) (n = 68 479, 45.1%), alcohol (n = 38 328, 25.2%), non-alcoholic steatohepatitis (NASH) (n = 17 485, 11.5%), liver tumors (n = 16 644, 11.0%), and other diseases (n = 10 928, 7.2%), median SVI was 59.3 (IQR, 40.1-83.4). SVI (76.2 vs. 24.3, p < .001) was greater in the highest versus lowest liver-related mortality quartiles. The travel distances to LT centers (143.1 miles vs. 107.2 miles, p < .001) was longer in the lowest versus highest LT registration quartiles. Counties with low LT registration rates and high liver-related mortality rates were associated with long travel distances and high SVI. In contrast, while counties with high LT registration rates and high liver-related mortality rates had comparable SVI, travel distance was relatively shorter. CONCLUSION: Counties with greater SVIs were associated with higher liver-related mortality, with the highest SVI  counties having the highest overall liver-related mortality. Longer travel distances were associated with higher liver-related mortality. These findings highlight the impact of social determinants of health (SDOH) on liver disease outcomes.

Predictors and Prognostic Significance of Postoperative Complications for Patients with Intrahepatic Cholangiocarcinoma.

BACKGROUND: The prognostic impact of major postoperative complications (POCs) for intrahepatic cholangiocarcinoma (ICC) remains ill-defined. We sought to analyze the relationship between POCs and outcomes relative to lymph node metastases (LNM) and tumor burden score (TBS). METHODS: Patients who underwent resection of ICC between 1990-2020 were included from an international database. POCs were defined according to Clavien-Dindo classification ≥ 3. The prognostic impact of POCs was estimated relative to TBS categories (i.e., high and low) and lymph node status (i.e., N0 or N1). RESULTS: Among 553 patients who underwent curative-intent resection for ICC, 128 (23.1%) individuals experienced POCs. Low TBS/N0 patients who experienced POCs presented with a higher risk of recurrence and death (3-year cumulative recurrence rate; POCs: 74.8% vs. no POCs: 43.5%, p = 0.006; 5-year overall survival [OS], POCs 37.8% vs. no POCs 65.8%, p = 0.003), while POCs were not associated with worse outcomes among high TBS and/or N1 patients. The Cox regression analysis confirmed that POCs were significant predictors of poor outcomes in low TBS/N0 patients (OS, hazard ratio [HR] 2.91, 95%CI 1.45-5.82, p = 0.003; recurrence free survival [RFS], HR 2.42, 95%CI 1.28-4.56, p = 0.007). Among low TBS/N0 patients, POCs were associated with early recurrence (within 2 years) (Odds ratio [OR] 2.79 95%CI 1.13-6.93, p = 0.03) and extrahepatic recurrence (OR 3.13, 95%CI 1.14-8.54, p = 0.03), in contrast to patients with high TBS and/or nodal disease. CONCLUSIONS: POCs were independent, negative prognostic determinants for both OS and RFS among low TBS/N0 patients. Perioperative strategies that minimize the risk of POCs are critical to improving prognosis, especially among patients harboring favorable clinicopathologic features.

The impact of tumor location on the value of lymphadenectomy for intrahepatic cholangiocarcinoma.

BACKGROUND: The therapeutic role of lymphadenectomy (LND) for intrahepatic cholangiocarcinoma (ICC) patients remains ill-defined. We sought to analyze the therapeutic value of LND relative to tumor location and preoperative lymph node metastasis (LNM) risk. METHODS: Patients who underwent curative-intent hepatic resection of ICC between 1990 and 2020 were included from a multi-institutional database. Therapeutic LND (tLND) was defined as LND that harvested ≥3 lymph nodes. RESULTS: Among 662 patients, 178 (26.9%) individuals received tLND. Patients were categorized into central type ICC (n = 156, 23.6%) and peripheral type ICC (n = 506, 76.4%). Central type harbored multiple adverse clinicopathologic factors and worse overall survival (OS) compared with peripheral type (5-year OS, central: 27.0% vs. peripheral: 47.2%, p < 0.001). After consideration of preoperative LNM risk, patients with central type and high-risk LNM who underwent tLND survived longer than individuals who did not (5-year OS, tLND: 27.9% vs. non-tLND: 9.0%, p = 0.001), whereas tLND was not associated with better survival among patients with peripheral type ICC or low-risk LNM. The therapeutic index of hepatoduodenal ligament (HDL) and other regions was higher in central type than in peripheral type, which was more pronounced among high-risk LNM patients. CONCLUSIONS: Central type ICC with high-risk LNM should undergo LND involving regions beyond the HDL.

Association between the environmental quality index and textbook outcomes among Medicare beneficiaries undergoing surgery for colorectal cancer (CRC).

BACKGROUND: Quality of cancer care received by individuals may be influenced by environmental factors resulting in inequalities within the healthcare system. We sought to investigate the association between the Environmental Quality Index (EQI) and achievement of textbook outcomes (TOs) among Medicare beneficiaries who underwent surgical resection for colorectal cancer (CRC). METHODS: Patients diagnosed with CRC from 2004 to 2015 were identified using the Surveillance, Epidemiology, and End Results-Medicare database and merged with the US Environmental Protection Agency's EQI data. A high EQI category indicated poor environmental quality, whereas a low EQI indicated better environmental conditions. RESULTS: Among 40 939 patients, 33 699 (82.3%) were diagnosed with colon cancer, 7240 (17.7%) were diagnosed with rectal cancer, and 652 (1.6%) were diagnosed with both cancers. Median age was 76 years old (interquartile range: 70-82 years) with roughly half of patients being female (n = 22 033, 53.8%). Most patients self-reported as White (n = 32 404, 79.2%) and resided in the West region of the United States (n = 20 308, 49.6%). On multivariable analysis, patients residing in high EQI areas were less likely to achieve TO (referent: low EQI; odds ratio [OR]: 0.94, 95% confidence interval [95% CI]: 0.89-0.99; p = 0.02). Of note, Black patients living in moderate-to-high EQI counties had a 31% decreased likelihood of reaching a TO compared with White patients in low EQI counties (OR: 0.69, 95% CI: 0.55-0.87). CONCLUSION: Patients residing in high EQI counties and Black race were associated with a lower likelihood of TO following resection of CRC among Medicare patients. Environmental factors may be important contributors to health care disparities and affect postoperative outcomes following CRC resection.

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.

Hospital Volume and Textbook Outcomes in Minimally Invasive Hepatectomy for Hepatocellular Carcinoma.

BACKGROUND: Hospital volume affects outcomes of patients who underwent resection for hepatocellular carcinoma (HCC). We sought to assess the impact of minimally invasive hepatectomy (MIH) volume on short- and long-term outcomes among patients with HCC. METHODS: Patients who underwent MIH for HCC from 2010 to 2018 were identified from the National Cancer Database. Multivariable modeling with restricted cubic splines (RCS) was utilized to identify the MIH hospital volume threshold. Textbook outcome (TO) was defined as no conversion to open resection, negative margins after resection (R0), no extended length-of-stay, no readmission, and no 90-day mortality. RESULTS: Among 3268 patients who underwent MIH for HCC, median age was 65.0 (IQR 59.0-72.0) and the majority was male (n = 2308, 70.6%). MIH hospital volume ranged from 1 to 87 cases, with a median of 13 (IQR 7-23). Overall, 2151 (60.9%) patients achieved TO after resection. While particularly high rates of achievement were found for no 90-day mortality (n = 3106, 95.0%), no readmission (n = 3153, 96.5%), and R0 resection (n = 3,017, 92.3%), other TO components including no conversion to open (n = 2778, 85.0%) and no prolonged LOS (n = 2584, 79.1%) were achieved less frequently. Patients treated at high-volume centers (≥50 MIH cases) were more likely to experience TO (high volume centers, n = 334, 68.7% vs. low volume centers, n = 1656, 59.5%, p < 0.001) and better long-term survival (5-year OS; high volume centers, 64.7% vs. low volume centers, 54.6%, p < 0.001). CONCLUSIONS: MIH hospital volume was associated with a higher likelihood of achieving TO and improved long-term survival among patients undergoing resection of HCC.

Preoperative risk score (PreopScore) to predict overall survival after resection for hepatocellular carcinoma.

BACKGROUND: This study aimed to develop a holistic risk score incorporating preoperative tumor, liver, nutritional, and inflammatory markers to predict overall survival (OS) after hepatectomy for hepatocellular carcinoma (HCC). METHODS: Patients who underwent curative-intent surgery for HCC between 2000 and 2020 were identified using an international multi-institutional database. Preoperative predictors associated with OS were selected and a prognostic risk score model (PreopScore) was developed and validated using cross-validation. RESULTS: A total of 1676 patients were included. On multivariable analysis, preoperative parameters associated with OS included α-feto protein (hazard ratio [HR]1.17, 95%CI 1.03-1.34), neutrophil-to-lymphocyte ratio (HR2.62, 95%CI 1.30-5.30), albumin (HR0.49, 95%CI 0.34-0.70), gamma-glutamyl transpeptidase (HR1.00, 95%CI 1.00-1.00), as well as vascular involvement (HR3.52, 95%CI 2.10-5.89) and tumor burden score (medium, HR3.49, 95%CI 1.62-7.58; high, HR3.21, 95%CI 1.40-7.35) on preoperative imaging. A weighted PreopScore was devised and made available online (https://yutaka-endo.shinyapps.io/PrepoScore_Shiny/). Patients with a PreopScore 0-2, 2-3.5, and >3.5 had incrementally worse 5-year OS of 85.8%, 70.7%, and 52.4%, respectively (p < 0.001). The c-index of the test and validation cohort were 0.75 and 0.71, respectively. The PreopScore outperformed individual parameters and previous HCC staging systems. DISCUSSION: The PreopScore can be used as a better guide to preoperatively identify patients and individualize pre-/post-operative strategies.

Variations in Textbook Oncologic Outcomes After Curative-Intent Resection: Early Versus Intermediate Hepatocellular Carcinoma Based on Barcelona Clinic Liver Cancer Criteria and Child-Pugh Classification.

BACKGROUND: The impact of early versus intermediate hepatocellular carcinoma (HCC) on short-term "optimal" outcomes remains ill-defined. This study sought to define the incidence of textbook oncologic outcomes (TOO), as well as to identify factors associated with TOO among patients with early versus intermediate HCC. METHODS: Patients who underwent curative-intent liver resection for HCC (1998-2020) were identified from a multi-institutional database. Textbook oncologic outcome (TOO) was defined as negative surgical margins, no return to the operating room, no extended hospital stay, no severe complications, and no 90-day mortality or readmission. Patients were stratified as early HCC (BCLC 0 or BCLC A/Child-Pugh A) or intermediate HCC (BCLC A/Child-Pugh B or BCLC B). Multivariate logistic regression analysis was used to assess factors associated with TOO. RESULTS: Among 1383 patients, the overall incidence of TOO was 69.0%. Patients with intermediate HCC were less likely to achieve a TOO (early [71.6 %] vs. intermediate [60.1%]; p < 0.001). On multivariate analysis, factors associated with decreased odds of a TOO were high tumor burden (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.33-1.00), high aspartate transaminase-platelet ratio index (APRI) (OR, 0.46; 95% CI, 0.30-0.70), Charlson Comorbidity Index (CCI) greater than 3 (OR, 0.67; 95% CI, 0.49-0.91), major liver resection (OR, 0.68; 95% CI, 0.52-0.90), and intermediate HCC (OR, 0.68; 95% CI, 0.50-0.93) (all p < 0.05). Notably, although high APRI, CCI greater than 3, and major liver resection contributed to lower odds of a TOO in early HCC, the only factor that adversely impacted TOO in intermediate HCC was high tumor burden. CONCLUSIONS: Patients with intermediate HCC and early HCC patients with liver dysfunction, comorbidities, or an extensive resection were less likely to achieve an "optimal" postoperative outcome.

Predictive risk-score model to select patients with intrahepatic cholangiocarcinoma for adjuvant chemotherapy.

BACKGROUND: The aim of this study was to develop a predictive model to identify individuals most likely to derive overall survival (OS) benefit from adjuvant chemotherapy (AC) after hepatic resection of intrahepatic cholangiocarcinoma (ICC). METHODS: Patients who underwent hepatic resection of ICC between 1990 and 2020 were identified from a multi-institutional database. Factors associated with worse OS were identified and incorporated into an online predictive model to identify patients most likely to benefit from AC. RESULTS: Among 726 patients, 189 (26.0%) individuals received AC. Factors associated with OS on multivariable analysis included CA19-9 (Hazard Ratio [HR]1.17, 95%CI 1.04-1.31), tumor burden score (HR1.09, 95%CI 1.04-1.15), T-category (T2/3/4, HR1.73, 95%CI 1.73-2.64), nodal disease (N1, HR3.80, 95%CI 2.02-7.15), tumor grade (HR1.88, 95%CI 1.00-3.55), and morphological subtype (HR2.19, 95%CI 1.08-4.46). A weighted predictive score was devised and made available online (https://yutaka-endo.shinyapps.io/ICCrisk_model_for_AC/). Receipt of AC was associated with a survival benefit among patients at high/medium-risk (high: no AC, 0% vs. AC, 20.6%; medium: no AC, 36.4% vs. 40.8%; both p < 0.05) but not low-risk (low: no AC, 65.1% vs. AC, 65.1%; p = 0.73) tumors. CONCLUSION: An online predictive model based on tumor characteristics may help identify which patients may benefit the most from AC following resection of ICC.