Conversion therapy for advanced hepatocellular carcinoma in the era of precision medicine: Current status, challenges and opportunities.

Hepatocellular carcinoma (HCC), the most prevalent malignancy of the digestive tract, is characterized by a high mortality rate and poor prognosis, primarily due to its initial diagnosis at an advanced stage that precludes any surgical intervention. Recent advancements in systemic therapies have significantly improved oncological outcomes for intermediate and advanced-stage HCC, and the combination of locoregional and systemic therapies further facilitates tumor downstaging and increases the likelihood of surgical resectability for initially unresectable cases following conversion therapies. This shift toward high conversion rates with novel, multimodal treatment approaches has become a principal pathway for prolonged survival in patients with advanced HCC. However, the field of conversion therapy for HCC is marked by controversies, including the selection of potential surgical candidates, formulation of conversion therapy regimens, determination of optimal surgical timing, and application of adjuvant therapy post-surgery. Addressing these challenges and refining clinical protocols and research in HCC conversion therapy is essential for setting the groundwork for future advancements in treatment strategies and clinical research. This narrative review comprehensively summarizes the current strategies and clinical experiences in conversion therapy for advanced-stage HCC, emphasizing the unresolved issues and the path forward in the context of precision medicine. This work not only provides a comprehensive overview of the evolving landscape of treatment modalities for conversion therapy but also paves the way for future studies and innovations in this field.

Prognostic Value of Serum α-Fetoprotein Level as an Important Characteristic of Tumor Biology for Patients Undergoing Liver Resection of Early-Stage Hepatocellular Carcinoma (BCLC Stage 0/A): A Large Multicenter Analysis.

BACKGROUND AND OBJECTIVE: According to the Barcelona Clinic Liver Cancer (BCLC) algorithm, tumor burden and liver function, but not tumor biology, are the key factors in determining tumor staging and treatment modality, and evaluating treatment prognosis. The serum α-fetoprotein (AFP) level is an important characteristic of hepatocellular carcinoma (HCC) biology, and we aimed to evaluate its prognostic value for patients undergoing liver resection of early-stage HCC. METHODS: Patients who underwent curative liver resection for early-stage HCC were identified from a multi-institutional database. Patients were divided into three groups according to preoperative AFP levels: low (< 400 ng/mL), high (400-999 ng/mL), and extremely-high (≥ 1000 ng/mL) AFP groups. Overall survival (OS) and recurrence rates were compared among these three groups. RESULTS: Among 1284 patients, 720 (56.1%), 262 (20.4%), and 302 (23.5%) patients had preoperative low, high, and extremely-high AFP levels, respectively. The cumulative 5-year OS and recurrence rates were 71.3 and 38.9% among patients in the low AFP group, 66.3 and 48.5% in the high AFP group, and 45.7 and 67.2% in the extremely-high AFP group, respectively (both p < 0.001). Multivariate Cox regression analysis identified both high and extremely-high AFP levels to be independent risk factors of OS (hazard ratio [HR] 1.275 and 1.978, 95% confidence interval [CI] 1.004-1.620 and 1.588-2.464, respectively; p = 0.047 and p < 0.001, respectively) and recurrence (HR 1.290 and 2.050, 95% CI 1.047-1.588 and 1.692-2.484, respectively; p = 0.017 and p < 0.001, respectively). CONCLUSIONS: This study demonstrated the important prognostic value of preoperative AFP levels among patients undergoing resection for early-stage HCC. Incorporating AFP to prognostic estimation of the BCLC algorithm can help guide individualized risk stratification and identify neoadjuvant/adjuvant treatment necessity.

Preoperative frailty as a key predictor of short- and long-term outcomes among octogenarians undergoing hepatectomy for hepatocellular carcinoma: a multicenter comprehensive analysis.

BACKGROUND: When considering hepatectomy for elderly HCC patients, it's essential to assess surgical safety and survival benefits. This study investigated the impact of preoperative frailty, assessed with the Clinical Frailty Scale (CFS), on outcomes for octogenarians undergoing HCC hepatectomy. METHODS: A retrospective cohort study of octogenarians who had hepatectomy for HCC between 2010 and 2022 at 16 hepatobiliary centers was conducted. Patients were categorized as frail or non-frail based on preoperative CFS, with frailty defined as CFS ≥5. The primary endpoints were overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival (CSS), with perioperative outcomes as secondary endpoints. RESULTS: Among 240 octogenarians, 105 were characterized as being frail. Frail patients had a higher incidence of postoperative 30-day morbidity and postoperative 30-day and 90-day mortality versus non-frail patients. Meanwhile, 5-year OS, RFS and CSS among frail patients were lower compared with non-frail patients. Univariable and multivariable analysis revealed that preoperative frailty was an independent risk factor of postoperative 30-day morbidity (OR: 2.060), OS (HR: 2.384), RFS (HR: 2.190) and CSS (HR: 2.203). CONCLUSION: Preoperative frailty, as assessed by the CFS, was strongly associated with both short-term outcomes and long-term survival among octogenarians undergoing hepatectomy for HCC. Incorporating frailty assessment into the preoperative evaluation may help optimize patient selection and perioperative care.

Association of Concurrent Metabolic Syndrome with Long-term Oncological Prognosis Following Liver Resection for Hepatocellular Carcinoma Among Patients with Chronic Hepatitis B Virus Infection: A Multicenter Study of 1753 Patients.

BACKGROUND: Although hepatitis B virus (HBV) infection remains the main cause of hepatocellular carcinoma (HCC) worldwide, metabolic syndrome, with its increase in prevalence, has become an important and significant risk factor for HCC. This study was designed to investigate the association of concurrent metabolic syndrome with long-term prognosis following liver resection for patients with HBV-related HCC. METHODS: From a Chinese, multicenter database, HBV-infected patients who underwent curative resection for HCC between 2010 and 2020 were identified. Long-term oncological prognosis, including overall survival (OS), recurrence-free survival (RFS), and early (≤2 years of surgery) and late (>2 years) recurrences were compared between patients with versus those without concurrent metabolic syndrome. RESULTS: Of 1753 patients, 163 (9.3%) patients had concurrent metabolic syndrome. Compared with patients without metabolic syndrome, patients with metabolic syndrome had poorer 5-year OS (47.5% vs. 61.0%; P = 0.010) and RFS (28.3% vs. 44.2%; P = 0.003) rates and a higher 5-year overall recurrence rate (67.3% vs. 53.3%; P = 0.024). Multivariate analysis revealed that concurrent metabolic syndrome was independently associated with poorer OS (hazard ratio: 1.300; 95% confidence interval: 1.018-1.660; P = 0.036) and RFS (1.314; 1.062-1.627; P = 0.012) rates, and increased rates of late recurrence (hazard ratio: 1.470; 95% confidence interval: 1.004-2.151; P = 0.047). CONCLUSIONS: In HBV-infected patients with HCC, concurrent metabolic syndrome was associated with poorer postoperative long-term oncologic survival outcomes. These results suggested that patients with metabolic syndrome should undergo enhanced surveillance for tumor recurrence even after 2 years of surgery to early detect late HCC recurrence. Whether improving metabolic syndrome can reduce postoperative recurrence of HCC deserves further exploration.

Prospective validation of the Eastern Staging in predicting survival after surgical resection for patients with hepatocellular carcinoma: a multicenter study from China.

BACKGROUND: The Eastern Staging System, which was specially developed for patients undergoing surgical resection for hepatocellular carcinoma (HCC), has been proposed for more than ten years. To prospectively validate the predictive accuracy of the Eastern staging on long-term survival after HCC resection. METHODS: Patients who underwent hepatectomy for HCC from 2011 to 2020 at 10 Chinese hospitals were identified from a prospectively collected database. The survival predictive accuracy was evaluated and compared between the Eastern Staging with six other staging systems, including the JIS, BCLC, Okuda, CLIP, 8th AJCC TNM, and HKLC staging. RESULTS: Among 2365 patients, the 1-, 3-, and 5-year overall survival rates were 84.2%, 64.5%, and 52.6%, respectively. Among these seven staging systems, the Eastern staging was associated with the best monotonicity of gradients (linear trend χ2: 408.5) and homogeneity (likelihood ratio χ2: 447.3), and the highest discriminatory ability (the areas under curves for 1-, 3-, and 5-year mortality: 0.776, 0.787, and 0.768, respectively). In addition, the Eastern staging was the most informative staging system in predicting survival (Akaike information criterion: 2982.33). CONCLUSION: Using a large multicenter prospectively collected database, the Eastern Staging was found to show the best predictive accuracy on long-term overall survival in patients with resectable HCC than the other 6 commonly-used staging systems.

Association of Preoperative Body Mass Index with Surgical Textbook Outcomes Following Hepatectomy for Hepatocellular Carcinoma: A Multicenter Study of 1206 Patients.

BACKGROUND: Assessment of quality in the perioperative period is critical to ensure good patient care. Textbook outcomes (TO) have been proposed to combine several parameters into a single defined quality metric. The association of preoperative body mass index (BMI) with incidences of achieving or not achieving TO (non-TO) among patients undergoing hepatectomy for hepatocellular carcinoma (HCC) was characterized. METHODS: Patients who underwent curative-intent hepatectomy for HCC between 2015 and 2018 were identified from a multicenter database. These patients were divided into three groups based on preoperative BMI: low-BMI (≤ 18.4 kg/m2), normal-BMI (18.5-24.9 kg/m2), and high-BMI (≥ 25.0 kg/m2). The incidences of non-TO among these three groups were compared. Multivariate analyses were performed to identify whether there was any independent association between preoperative BMI and non-TO. RESULTS: Among 1206 patients, 100 (8.3%), 660 (54.7%), and 446 (37.0%) were in the low-BMI, normal-BMI, and high-BMI groups, respectively. The incidence of non-TO was 65.6% in the whole cohort. The incidence of non-TO was significantly higher among patients in the low- and high-BMI cohorts versus the normal-BMI cohort (75.0% and 74.7% versus 58.0%, both P < 0.01). After adjustment of other confounding factors on multivariate analysis, low-BMI and high-BMI were independently associated with higher incidences of non-TO compared with normal-BMI (OR: 1.98 and 2.27, both P < 0.05). CONCLUSIONS: Two out of three patients did not achieve TO after hepatectomy for HCC. Both preoperative low-BMI and high-BMI were independently associated with lower odds to achieve optimal TO following HCC resection.

Clinical Features of Recurrence After Hepatic Resection for Early-Stage Hepatocellular Carcinoma and Long-Term Survival Outcomes of Patients with Recurrence: A Multi-institutional Analysis.

BACKGROUND: A potentially curative hepatic resection is the optimal treatment for hepatocellular carcinoma (HCC), but most HCCs, even at an early stage, eventually recur after resection. This study investigates clinical features of initial recurrence and long-term prognosis of patients with recurrence after curative resection for early-stage HCC. PATIENTS AND METHODS: From a multicenter database, patients who underwent curative hepatic resection for early-stage HCC [Barcelona Clinic Liver Cancer (BCLC) stage 0/A] were extracted. Time to initial recurrence, patterns of initial recurrence, and treatment modalities for recurrent tumors were investigated. Univariate and multivariate analysis were used to identify independent risks associated with postoperative recurrence, as well as post-recurrence survival (PRS) for patients with recurrence. RESULTS: Among 1424 patients, 679 (47.7%) developed recurrence at a median follow-up of 54.8 months, including 408 (60.1%) early recurrence (≤ 2 years after surgery) and 271 (39.9%) late recurrence (> 2 years). Independent risks of postoperative recurrence included cirrhosis, preoperative alpha-fetoprotein level > 400 ug/L, tumor size > 5 cm, multiple tumors, satellites, microvascular invasion, and intraoperative blood transfusion. Multivariate analysis revealed that receiving irregular recurrence surveillance, initial tumor beyond Milan criteria, early recurrence, BCLC stage B/C of the recurrent tumor, and noncurative treatments were independently associated with poorer PRS. CONCLUSIONS: Nearly half of patients with early-stage HCC experienced recurrence after resection. Understanding recurrence risks may help identify patients at high risk of recurrence who may benefit from future adjuvant therapies. Meaningful survival even after recurrence can still be achieved by postoperative regular surveillance and curative treatment.

Deciphering the Role of Necroptosis-Related Long Non-coding RNAs in Hepatocellular Carcinoma: A Necroptosis-Related lncRNA-Based Signature to Predict the Prognosis of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer, characterized by a high morbidity rate. Long non-coding RNAs (lncRNAs) play an important role in regulating various cellular processes and diseases, including cancer. However, their specific roles and mechanisms in HCC are not fully understood. This study used a multi-cohort design to investigate necroptosis-related lncRNAs (NRLs) in patients with HCC. We curated a list of 1095 NRLs and 838 genes showing differential expression between tumor and normal tissues. Among them, we found 105 NRLs closely associated with the prognosis of HCC patients. The 10 lncRNAs (AC100803.3, AC027237.2, AL158166.1, LINC02870, AC026412.3, LINC02159, AC027097.1, AC139887.4, AC007405.1, AL023583.1) generated by LASSO-Cox regression analysis were used to create a prognostic risk model for HCC and group patients into groups based on risk. The KEGG analysis revealed distinct pathway enrichments in high-risk (H-R) and low-risk (L-R) subgroups. According to GO analysis, this study identified 230 differentially expressed genes (DEGs) that were significantly enriched in specific biological processes. Comparison of immune checkpoint-related genes (MCPGs) between H-R and L-R patients revealed significant differences. Moreover, we established a correlation between the risk scores of patients with liver cancer and their sensitivity to 16 chemotherapeutic agents. Employing protein-protein interaction (PPI) analysis, we identified 10 hub genes that potentially regulate the molecular networks involved in HCC development. This study is a pioneering effort to investigate the roles of NRLs in HCC. It opens a new avenue for potential targeted therapies and provides insights into the molecular mechanisms of HCC.

Grading severity of microscopic vascular invasion was independently associated with recurrence and survival following hepatectomy for solitary hepatocellular carcinoma.

Background: Hepatectomy is the preferred treatment for solitary hepatocellular carcinoma (HCC) without macrovascular invasion and distant metastasis, but long-term survival remains unsatisfactory in certain patients. We sought to identify whether the grading severity of microscopic vascular invasion (MVI) was associated with recurrence and survival among patients with solitary HCC. Methods: Consecutive patients who underwent hepatectomy for solitary HCC were identified from a multicenter prospectively-collected database. Patients were categorized into three groups according to the MVI grading system proposed by the Liver Cancer Pathology Group of China: M0 (no MVI), M1 (1-5 sites of MVI occurring ≤1.0 cm away from the tumor), and M2 (>5 sites occurring ≤1.0 cm or any site occurring >1 cm away from the tumor). Recurrence-free survival (RFS) and overall survival (OS) were compared among the groups. Results: Among 227 patients, 97 (42.7%), 83 (36.6%), and 47 (20.7%) patients had M0, M1, and M2, respectively. Median RFS rates among patients with M0, M1, and M2 were 38.3, 35.1, 11.6 months, respectively, while OS rates were 66.8, 62.3, 30.6 months, respectively (both P<0.001). Multivariate Cox-regression analyses demonstrated that both M1 and M2 were independent risk factors for RFS (hazard ratio 1.20, 95% CI: 1.03-1.89, P=0.040; and hazard ratio 1.67, 95% CI: 1.06-2.64, P=0.027) and OS (hazard ratio 1.28, 95% CI: 1.05-2.07, P=0.035; and hazard ratio 1.97, 95% CI: 1.15-3.38, P=0.013). Conclusions: Grading severity of MVI was independently associated with RFS and OS after hepatectomy for solitary HCC. Enhanced surveillance for recurrence and potentially adjuvant therapy may be considered for patients with MVI, especially individuals with more severe MVI grading (M2).

Development and validation of prealbumin-bilirubin score (preALBI score) for predicting long-term survival after hepatectomy for hepatocellular carcinoma: A multicenter analysis versus ALBI score.

BACKGROUND: The Albumin-Bilirubin (ALBI) score, widely used in predicting long-term prognosis for patients with hepatocellular carcinoma (HCC), has limitations due to serum albumin variability. This study aimed to develop and validate the Prealbumin-Bilirubin (preALBI) score as a reliable alternative. METHODS: A multicenter cohort of HCC patients who underwent hepatectomy was randomly divided into the training and validation cohorts. The preALBI score was developed using Cox regression models within the training cohort, incorporating serum prealbumin and bilirubin levels as crucial determinants. The survival predictive accuracy was evaluated and compared between the preALBI score with two other staging systems, including the ALBI score and the Child-Pugh grade. RESULTS: A total of 2409 patients were enrolled. In the training cohort, the preALBI score demonstrated superior performance in predicting long-term survival after hepatectomy. The preALBI score was associated with the best monotonicity of gradients (linear trend χ2: 72.84) and homogeneity (likelihood ratio χ2: 74.69), and the highest discriminatory ability (the areas under curves for 1-, 3-, and 5-year mortality: 0.663, 0.654, and 0.644, respectively). In addition, the preALBI was the most informative staging system in predicting survival (Akaike information criterion: 11325.65).The results remained consistent in both training and validation cohorts, indicating its reliable performance across different populations. CONCLUSION: The preALBI score, leveraging the stability of prealbumin, represents a promising tool for better patient stratification, providing more accurate prognostic predictions than the ALBI score and the Child-Pugh grade.

Development and validation of nomograms to predict survival and recurrence after hepatectomy for intermediate/advanced (BCLC stage B/C) hepatocellular carcinoma.

BACKGROUND: Despite the Barcelona Clinic Liver Cancer system discouraging hepatectomy for intermediate/advanced hepatocellular carcinoma, the procedure is still performed worldwide, particularly in Asia. This study aimed to develop and validate nomograms for predicting survival and recurrence for these patients. METHODS: We analyzed patients who underwent curative-intent hepatectomy for intermediate/advanced hepatocellular carcinoma between 2010 and 2020 across 3 Chinese hospitals. The Eastern Hepatobiliary Surgery Hospital cohort was used as the training cohort for the nomogram construction, and the Jilin First Hospital and Fujian Mengchao Hepatobiliary Hospital cohorts served as the external validation cohorts. Independent preoperative predictors for survival and recurrence were identified through univariable and multivariable Cox regression analyses. Predictive accuracy was measured using the concordance index and calibration curves. The predictive performance between nomograms and conventional hepatocellular carcinoma staging systems was compared. RESULTS: A total of 1,328 patients met the inclusion criteria. The nomograms for predicting survival and recurrence were developed using 10 and 6 independent variables, respectively. Nomograms' concordance indices in the training cohort were 0.777 (95% confidence interval 0.759-0.800) and 0.719 (95% confidence interval 0.697-0.742) for survival and recurrence, outperforming 4 conventional staging systems (P < .001). Nomograms accurately stratified risk into low, intermediate, and high subgroups. These results were validated well by 2 external validation cohorts. CONCLUSION: We developed and validated nomograms predicting survival and recurrence for patients with intermediate/advanced hepatocellular carcinoma, contradicting Barcelona Clinic Liver Cancer surgical guidelines. These nomograms may facilitate clinicians to formulate personalized surgical decisions, estimate long-term prognosis, and strategize neoadjuvant/adjuvant anti-recurrence therapy.

Association of Pringle maneuver with postoperative recurrence and survival following hepatectomy for hepatocellular carcinoma: a multicenter propensity score and competing-risks regression analysis.

Background: The application of Pringle maneuver (PM) during hepatectomy reduces intraoperative blood loss and the need for perioperative transfusion, but its effect on long-term recurrence and survival for patients with hepatocellular carcinoma (HCC) remains controversial. We sought to determine the association between the application of PM and post-hepatectomy oncologic outcomes for patients with HCC. Methods: Patients who underwent curative hepatectomy for HCC at 9 Chinese hospitals from January 2010 to December 2018 were identified. Using two propensity score methods [propensity score matching (PSM) and inverse probability of treatment weight (IPTW)], cumulative recurrence rate and cancer-specific mortality (CSM) were compared between the patients in the PM and non-PM groups. Multivariate competing-risks regression models were performed to adjust for the effect of non-cancer-specific mortality and other prognostic risk factors. Results: Of the 2,798 included patients, 2,404 and 394 did and did not adopt PM (the PM and non-PM groups), respectively. The rates of intraoperative blood transfusion, postoperative 30-day mortality and morbidity were comparable between the two groups (all P>0.05). In the PSM cohort by the 1:3 ratio, compared to 382 patients in the non-PM group, 1,146 patients in the PM group also had the higher cumulative 5-year recurrence rate and CSM (63.9% and 39.1% vs. 55.3% and 31.6%, both P<0.05). Similar results were also yielded in the entire cohort and the IPTW cohort. Multivariate competing-risks regression analyses demonstrated that no application of the PM was independently associated with lower recurrence rate and CSM based on various analytical cohorts [hazard ratio (HR), 0.82 and 0.77 in the adjusted entire cohort, HR 0.80 and 0.73 in the PSM cohort, and HR 0.80 and 0.76 in the IPTW cohort, respectively]. Conclusions: The findings suggested that no application of PM during hepatectomy for patients with HCC reduced the risk of postoperative recurrence and cancer-specific death by approximately 20-25%.

Long-term outcomes following hepatectomy in patients with lean non-alcoholic fatty liver disease-associated hepatocellular carcinoma versus overweight and obese counterparts: A multicenter analysis.

BACKGROUND & AIMS: With the rising prevalence of non-alcoholic fatty liver disease (NAFLD) as a significant etiology for hepatocellular carcinoma (HCC), lean NAFLD-HCC has emerged as a specific distinct subtype. This study sought to investigate long-term outcomes following curative-intent hepatectomy for early-stage NAFLD-HCC among lean patients compared with overweight and obese individuals. METHODS: A multicenter retrospective analysis was used to assess early-stage NAFLD-HCC patients undergoing curative-intent hepatectomy between 2009 and 2022. Patients were stratified by preoperative body mass index (BMI) into the lean (<23.0 kg/m2), overweight (23.0-27.4 kg/m2) and obese (≥27.5 kg/m2) groups. Study endpoints were overall survival (OS) and recurrence-free survival (RFS), which were compared among groups. RESULTS: Among 309 patients with NAFLD-HCC, 66 (21.3 %), 176 (57.0 %), and 67 (21.7 %) were lean, overweight, and obese, respectively. The three groups were similar relative to most liver, tumor, and surgery-related variables. Compared with overweight patients (71.3 % and 55.6 %), the lean individuals had a worse 5-year OS and RFS (55.4 % and 35.1 %, P = 0.017 and 0.002, respectively), which were comparable to obese patients (48.5 % and 38.2 %, P = 0.939 and 0.442, respectively). After adjustment for confounding factors, multivariable Cox-regression analysis identified that lean bodyweight was independently associated with decreased OS (hazard ratio: 1.69; 95 % confidence interval: 1.06-2.71; P = 0.029) and RFS (hazard ratio: 1.72; 95 % confidence interval: 1.17-2.52; P = 0.006) following curative-intent hepatectomy for early-stage NAFLD-HCC. CONCLUSIONS: Compared with overweight patients, individuals with lean NAFLD-HCC had inferior long-term oncological survival after hepatectomy for early-stage NAFLD-HCC. These data highlight the need for examination of the distinct carcinogenic pathways of lean NAFLD-HCC and its potential consequences in HCC recurrence.

Stratifying risk of failure to achieve textbook outcomes among patients undergoing hepatectomy for hepatocellular carcinoma: A multicenter score validation study.

BACKGROUND AND AIMS: The concept of textbook outcomes (TOs) has gained increased attention as a critical metric to assess the quality and success of outcomes following complex surgery. A simple yet effective scoring system was developed and validated to predict risk of not achieving textbook outcomes (non-TOs) following hepatectomy for hepatocellular carcinoma (HCC). METHODS: Using a multicenter prospectively collected database, risk factors associated with non-TO among patients who underwent hepatectomy for HCC were identified. A predictive scoring system based on factors identified from multivariate regression analysis was used to risk stratify patients relative to non-TO. The score was developed using 70 % of the overall cohort and validated in the remaining 30 %. RESULTS: Among 3681 patients, 1458 (39.6 %) failied to experience a TO. Based on the derivation cohort, obesity, American Society of Anaesthesiologists score(ASA score), Child-Pugh grade, tumor size, and extent of hepatectomy were identified as independent predictors of non-TO. The scoring system ranged from 0 to 10 points. Patients were categorized into low (0-3 points), intermediate (4-6 points), and high risk (7-10 points) of non-TO. In the validation cohort, the predicted risk of developing non-TOs was 39.0 %, which closely matched the observed risk of 39.9 %. There were no differences among the predicted and observed risks within the different risk categories. CONCLUSIONS: A novel scoring system was able to predict risk of non-TO accurately following hepatectomy for HCC. The score may enable early identification of individuals at risk of adverse outcomes and inform surgical decision-making, and quality improvement initiatives.