Search

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., (© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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 χ 2 : 72.84) and homogeneity (likelihood ratio χ 2 : 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., Competing Interests: Declaration of competing interest We confirm that this work is original and has not previously been published. None of the authors have any financial disclosures or conflict of interest. Approval for this study was obtained from the Ethics Committee of the participating hospitals. All the authors have been involved in the design, performance, and interpretation of data of this study, and in drafting the article and its critical revision., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., (© 2023. Society of Surgical Oncology.)

Background & Aims: The effectiveness of adjuvant immunotherapy to diminish recurrence and improve long-term prognosis following curative-intent surgical resection for hepatocellular carcinoma (HCC) is of increased interest, especially among individuals at high risk of recurrence. The objective of the current study was to investigate the impact of adjuvant immunotherapy on long-term recurrence and survival after curative resection among patients with intermediate/advanced HCC., Methods: Using a prospectively-collected multicenter database, patients who underwent curative-intent resection for Barcelona Clinic Liver Cancer (BCLC) stage B/C HCC were identified. Propensity score matching (PSM) analysis was used to compare recurrence-free survival (RFS) and overall survival (OS) between patients treated with and without adjuvant immune checkpoint inhibitors (ICIs). Multivariate Cox-regression analysis further identified independent factors of RFS and OS., Results: Among the 627 enrolled patients, 109 patients (23.3%) received adjuvant immunotherapy. Most ICI-related adverse reactions were grading I-II. PSM analysis created 99 matched pairs of patients with comparable baseline characteristics between patients treated with and without adjuvant immunotherapy. In the PSM cohort, the median RFS (29.6 vs. 19.3 months, P =0.031) and OS (35.1 vs. 27.8 months, P =0.036) were better among patients who received adjuvant immunotherapy versus patients who did not. After adjustment for other confounding factors on multivariable analyzes, adjuvant immunotherapy remained independently associated with favorable RFS (HR: 0.630; 95% CI: 0.435-0.914; P =0.015) and OS (HR: 0.601; 95% CI: 0.401-0.898; P =0.013). Subgroup analyzes identified potentially prognostic benefits of adjuvant immunotherapy among patients with intermediate-stage and advanced-stage HCC., Conclusion: This real-world observational study demonstrated that adjuvant immunotherapy was associated with improved RFS and OS following curative-intent resection of intermediate/advanced HCC. Future randomized controlled trials are warranted to establish definitive evidence for this specific population at high risks of recurrence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Xu, Wang, Xu, Fan, Diao, Chen, Jia, Liu, Zeng, Wang, Wu, Qiu, Li, Pawlik, Lau, Shen, Lv and Yang.)

Objectives: Hepatocellular carcinoma (HCC) is a common indication for hepatectomy that is often complicated by postoperative complication. The authors sought to investigate the relationship between the open with laparoscopic approach of hepatectomy and incidences of postoperative infectious complications., Patients and Methods: Using a multicenter database, HCC patients who underwent laparoscopic hepatectomy (LH) or open hepatectomy (OH) were reviewed and analyzed. Propensity score matching (PSM), inverse probability of treatment weight (IPTW), and multivariate logistic regression analyses were utilized to assess the association of the operative approach with postoperative infectious complications, including incisional surgical site infection (SSI), organ/space SSI, and remote infection (RI)., Results: Among 3876 patients, 845 (21.8%) and 3031 (78.2%) patients underwent LH and OH, respectively. The overall incidence of infection was 6.9 versus 14.6% among patients who underwent LH versus OH, respectively ( P <0.001). Of note, the incidences of incisional SSI (1.8 vs. 6.3%, P <0.001), organ/space SSI (1.8 vs. 4.6%, P <0.001), and RI (3.8 vs. 9.8%, P <0.001) were all significantly lower among patients who underwent LH versus OH. After PSM (6.9, 1.8, 1.8, and 3.8% vs. 18.5, 8.4, 5.2, and 12.8%, respectively) and IPTW (9.5, 2.3, 2.1, and 5.5% vs. 14.3, 6.3, 4.5, and 9.8%, respectively), LH remained associated with statistically lower incidences of all types of infectious complications. After adjustment for other confounding factors on multivariate analyses, LH remained independently associated with lower incidences of overall infection, incisional SSI, organ/space SSI, and RI in the overall, PSM, and IPTW cohorts, respectively., Conclusion: Compared with open approach, laparoscopic approach was independently associated with lower incidences of postoperative infectious complications following hepatectomy for HCC., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The presence of microvascular invasion (MVI) is a significant malignant pathological feature related to recurrence and survival after liver resection for hepatocellular carcinoma (HCC). This study aimed to investigate the relationship between the severity in the grading of MVI and long-term oncological outcomes in patients with early-stage HCC., Methods: A retrospective study was conducted on a prospectively maintained multicenter database on patients who underwent curative resection for Barcelona Clinic Liver Cancer stage 0/A HCC between 2017 and 2020. Patients were classified into three groups according to the severity in the grading of MVI: M0 (no MVI), M1 (1-5 sites of MVI occurring ≤1 cm away from the tumor), and M2 (>5 sites occurring ≤1 cm and/or any site occurring >1 cm away from the tumor). Recurrence-free survival (RFS) and overall survival (OS) were compared among the groups., Results: Of 388 patients, M0, M1, and M2 of the MVI gradings were present in 223 (57.5%), 118 (30.4%), and 47 (12.1%) patients, respectively. The median OS and RFS in patients with M0, M1, and M2 were 61.1, 52.7, and 27.4 months; and 43.0, 29.1, and 13.1 months (both P <0.001), respectively. Multivariable analyses identified both M1 and M2 to be independent risk factors for OS [hazard ratio (HR): 1.682, P =0.003; and HR: 3.570, P <0.001] and RFS (HR: 1.550, P =0.037; and HR: 2.256, P <0.001)., Conclusion: The severity in the grading of MVI was independently associated with recurrence and survival after HCC resection. Patients with the presence of MVI, especially those with a more severe MVI grading (M2), require more stringent recurrence surveillance and/or active adjuvant therapy against recurrence., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) remains controversial, especially for tumors larger than 5 cm. We compared the short- and long-term outcomes of laparoscopic and open liver resection (OLR) for large HCC., Methods: Patients with large HCC after curative hepatectomy were enrolled. To compare the short-term outcomes, propensity score matching (PSM) and inverse probability treatment weighting (IPTW) were performed to reduce the effect of confounding factors, respectively. Subsequently, Cox-regression analyses were conducted to identify the independent risk factors associated with decreased recurrence-free survival (RFS) and poor overall survival (OS)., Result: There were 265 patients enrolled in the final analysis: 146 who underwent OLR and 119 who underwent LLR. There was no significant difference between the OLR and LLR groups according to PSM and IPTW analysis (all P > 0.05). Multivariable analysis revealed that LLR was not independently associated with poorer OS (HR 1.15, 95% CI 0.80-1.67, P = 0.448) or RFS (HR 1.22, 95% CI 0.88-1.70, P = 0.238)., Conclusion: There were no significant differences in perioperative complications or long-term prognosis between LLR and OLR for large HCC, which provides evidence for standard laparoscopic surgical practice with adequate surgeon experience and careful patient selection., (© 2022. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

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., (© 2022. Society of Surgical Oncology.)

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 χ 2 : 408.5) and homogeneity (likelihood ratio χ 2 : 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., (Copyright © 2022 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Purpose: R0 resection with a wide surgical margin is the gold standard for hepatocellular carcinoma (HCC), yet R0 resection with narrow margins and even R1 resection is not uncommon in real-world clinical practice. We sought to use a propensity-matched analysis to characterize the efficacy of adjuvant radiation therapy on long-term oncological survival after hepatectomy for HCC with narrow or positive margins., Methods and Materials: Using a multi-institutional database, patients with HCC who underwent hepatectomy with negative margins of 0.1 to 1.0 cm or pathologically positive margins were analyzed. Using propensity score matching (PSM) and multivariate Cox-regression analysis, the effect of adjuvant radiation therapy on long-term overall survival (OS) and recurrence-free survival (RFS) was evaluated., Results: Among 683 patients who met inclusion criteria, 82 patients received adjuvant radiation therapy within 10 weeks after surgery. Radiation therapy-related major toxic effects were minimal among patients receiving adjuvant radiation therapy. PSM analysis created 78 matched pairs of patients. In the PSM cohort, median OS and RFS among patients treated with adjuvant radiation therapy were more favorable than individuals who were not treated (72.5 and 37.3 months versus 52.5 and 24.0 months, both P < .05). After adjustment for other confounding factors on multivariate analyses, adjuvant radiation therapy remained independently associated with favorable OS and RFS after hepatectomy with close/positive surgical margins for HCC (hazard ratios, 0.821 and 0.827, respectively)., Conclusions: Despite the lack of consensus on the role of adjuvant radiation therapy after HCC resection, this PSM analysis suggested improved OS and RFS with adjuvant radiation therapy after hepatectomy with close/positive surgical margins for HCC. Future randomized controlled trials are needed to further define the survival benefit of adjuvant radiation therapy for patients with HCC., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Alpha-fetoprotein (AFP) and prothrombin induced by vitamin K absence-II (PIVKA-II) are two commonly used biomarkers for detection and prognostic prediction of hepatocellular carcinoma (HCC). This study sought to evaluate and compare the use of these two biomarkers to detect HCC, as well as predict postoperative early recurrence (within 2 years after HCC resection)., Methods: Data on consecutive patients who underwent curative resection for HCC between 2014 and 2020 was prospectively collected and reviewed. Serum AFP and PIVKA-II levels within one week before surgery or at the time of detection of early recurrence were assessed; preoperative AFP positivity (≥20 ng/ml) and preoperative PIVKA-II positivity (≥40 mAU/ml) were examined relative to recurrence using univariate and multivariate Cox-regression analyses., Results: Among 751 patients who underwent curative HCC resection, 589 (78.4%) patients had preoperative PIVKA-II positivity versus 498 (66.3%) patients had preoperative AFP positivity (P < 0.001). With a median follow-up of 41.6 months, 370 (50.1%) patients had an early HCC recurrence; among patients with an early recurrence, the proportion of patients with PIVKA-II positivity versus AFP positivity (76.5% vs. 60.0%, P = 0.002) was higher. On multivariate analysis, preoperative PIVKA-II positivity, but not preoperative AFP positivity was an independent risk factor to predict early recurrence after HCC resection., Conclusions: AFP and PIVKA-II are useful biomarkers to detect resectable HCC and predict early recurrence after HCC resection, with the latter showing higher rates of positivity. Preoperative PIVKA-II positivity was independently associated with early recurrence following HCC resection., Competing Interests: Declaration of competing interest All authors have no conflicts of interest to declare., (Copyright © 2022 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Purpose: Portal hypertension due to cirrhosis is common among patients with hepatocellular carcinoma (HCC). This study aimed to compare the outcomes of partial hepatectomy in patients with HCC and clinically significant portal hypertension (CSPH) with or without concurrent splenectomy and esophagogastric devascularization (CSED)., Patients and Methods: From a multicenter database, patients with HCC and CSPH who underwent curative-intent hepatectomy were identified. Postoperative morbidity and mortality, and long-term overall survival (OS) were compared in patients with and without CSED before and after propensity score matching (PSM)., Results: Of the 358 enrolled patients, 86 patients underwent CSED. Before PSM, the postoperative 30-day morbidity and mortality rates were comparable between the CSED and non-CSED group (both P > 0.05). Using PSM, 81 pairs of patients were created. In the PSM cohort, the 5-year OS rate of the CSED group were significantly better than the non-CSED group (52.9% vs. 36.5%, P= 0.046). The former group had a significantly lower rate of variceal bleeding on follow-up (7.4% vs. 21.7%, P= 0.014). On multivariate analysis, CSED was associated with significantly better OS (HR: 0.39, P < 0.001)., Conclusion: Hepatectomy and CSED can safely be performed in selected patients with HCC and CSPH, which could improve postoperative prognosis by preventing variceal bleeding, and prolonging long-term survival., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: The impact of diabetes mellitus (DM) on the survival of patients with hepatocellular carcinoma (HCC) is still unclear. The present study aims to draw a firm conclusion in terms of evaluating the impact of DM on the prognosis of HCC after hepatectomy., Methods: The pattern of recurrence for HCC was often stratified into early-stage (<2 years) and late-stage (≥2 years) recurrence. Because the early-stage recurrence was mainly attributed to aggressive tumor pathological characteristics, patients who recurrence or die within 2 years were excluded. Cumulative overall survival (OS) and recurrence-free survival (RFS) were determined by the method of Kaplan-Meier, and the independent risk factors of OS/RFS were determined by Cox regression analysis., Results: A total of 426 patients were eventually included. The 3- and 5-year OS in patients with and without DM was 83.7%, 55.1%; and 90.9%, 77.4%, respectively. Multivariate analysis showed that DM was an independent risk factor for OS (HR 1.166, 95% CI 1.056-2.036, P = 0.022) and RFS (HR 1.365, 95% CI 1.043-1.787, P = 0.023)., Conclusion: DM is an independent risk factor for long-term prognosis in patients with HCC. Patients with DM after hepatectomy for HCC, thus, need to actively control DM and closer follow-up.

Background: Hepatocellular carcinoma (HCC) is the most common malignancy in the elderly worldwide, but it is also common among younger individuals in areas with endemic hepatitis B virus infection. The differences in long-term oncological prognosis of young versus elderly patients after R0 liver resection for HCC were explored in this study., Methods: Using a Chinese multicentre database, consecutive patients who underwent R0 liver resection for HCC between 2007 and 2019 were analysed retrospectively. After excluding middle-aged (36-69 years old) patients, overall survival (OS), cancer-specific survival (CSS), and recurrence were compared between young (35 years or younger) and elderly (70 years or older) patients using propensity score matching (PSM)., Results: Among 531 enrolled patients, there were 192 (36.2 per cent) and 339 (63.8 per cent) patients categorized as young and elderly respectively. PSM created 140 pairs of matched patients. In the PSM cohort, 5-year OS was comparable for young versus elderly patients (51.7 versus 52.3 per cent, P = 0.533). Young patients, however, had a higher 5-year cumulative recurrence rate (62.1 versus 51.6 per cent, P = 0.011) and a worse 5-year CSS rate (54.0 versus 64.3 per cent, P = 0.034) than elderly patients. On multivariable Cox regression analyses, young patient age remained independently associated with an increased recurrence rate (hazard ratio 1.62, P = 0.016) and a decreased CSS rate (hazard ratio 1.69, P = 0.021) compared with older age., Conclusion: Following R0 liver resection for HCC, younger patients were at a higher risk of recurrence, and elderly patients had a better CSS rate. Thus, enhanced surveillance for HCC recurrence should be implemented for young patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of BJS Society Ltd.)

Background: Hepatocellular carcinoma (HCC) is common among adolescents and young adults (AYAs) in areas with endemic hepatitis B virus infection. We sought to characterize clinical features and long-term outcomes among AYAs versus older adults (OAs) who underwent HCC resection., Methods: From a Chinese multicenter database, patients were categorized as AYA (aged 13-39 years) versus OA (aged ≥40 years). Patient clinical features, perioperative outcomes, overall survival (OS) and time-to-recurrence (TTR) were compared. Multivariable Cox-regression analyses were performed to identify the impact of age on OS and TTR., Results: Among 1952 patients, 354(22.2%) were AYAs. AYAs were less likely to have cirrhosis yet were likely to have advanced tumor pathological characteristics than OAs. Postoperative morbidity and mortality were comparable. Compared with OAs, AYAs had a comparable OS but a decreased TTR. Multivariable analyses identified that young age (<40 years) was independently associated with poorer TTR., Conclusions: Compared with OAs, AYAs had a higher incidence of recurrence following liver resection among patients with HCC, suggesting that enhanced surveillance for postoperative recurrence may be required among AYAs., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background & Aims: Postoperative morbidity following hepatectomy for hepatocellular carcinoma (HCC) is common and its impact on long-term oncological outcome remains unclear. This study aimed to investigate if postoperative morbidity impacts long-term survival and recurrence following hepatectomy for HCC., Methods: The data from a multicenter Chinese database of curative-intent hepatectomy for HCC were analyzed, and independent risks of postoperative 30-day morbidity were identified. After excluding patients with postoperative early deaths (≤90 days), early (≤2 years) and late (>2 years) recurrence rates, overall survival (OS), and time-to-recurrence (TTR) were compared between patients with and without postoperative morbidity., Results: Among 2,161 patients eligible for the study, 758 (35.1%) had postoperative 30-day morbidity. Multivariable logistic regression analysis showed that diabetes mellitus, obesity, Child-Pugh grade B, cirrhosis, and intraoperative blood transfusion were independent risks of postoperative morbidity. The rates of early and late recurrence among patients with postoperative morbidity were higher than those without (50.7% vs. 38.8%, P < 0.001; and 41.7% vs. 34.1%, P = 0.017). Postoperative morbidity was associated with decreased OS (median: 48.1 vs. 91.6 months, P < 0.001) and TTR (median: 19.8 vs. 46.1 months; P < 0.001). After adjustment of confounding factors, multivariable Cox-regression analyses revealed that postoperative morbidity was associated with a 27.8% and 18.7% greater likelihood of mortality (hazard ratio 1.278; 95% confidence interval: 1.126-1.451; P < 0.001) and recurrence (1.187; 1.058-1.331; P = 0.004)., Conclusion: This large multicenter study provides strong evidence that postoperative morbidity adversely impacts long-term oncologic prognosis after hepatectomy for HCC. The prevention and management of postoperative morbidity may be oncologically important., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Prealbumin is a more sensitive serum biomarker in reflecting liver function and nutritional status than albumin, because of its shorter half-life and its characteristics that could hardly be affected by supplemental venous infusion of albumin or blood transfusion. This study aimed to identify whether preoperative prealbumin level was associated with postoperative mortality and morbidity after hepatic resection for patients with hepatocellular carcinoma (HCC)., Methods: From a Chinese multicenter database, patients who underwent hepatic resection for HCC were divided into the low and normal prealbumin groups by using 17 mg/dL as the cut-off level for serum prealbumin taken within a week before surgery. Using univariable and multivariable logistic regression analyses, independent predictors associated with postoperative 30-day and 90-day mortality, 30-day overall and major morbidity, and postoperative hepatic insufficiency were identified., Results: Among 1356 patients, 409 (30.2%) had a low preoperative prealbumin level. Postoperative 30-day and 90-day mortality, and 30-day overall and major morbidity in the low prealbumin group were significantly higher than the normal prealbumin group (2.9% vs. 0.5%, 5.1% vs. 1.5%, 35.7% vs. 18.4%, and 14.4% vs. 6.5%, respectively, all P < 0.001). Multivariable analyses identified that preoperative prealbumin level, but not albumin level, was independently associated with postoperative 30-day mortality (OR: 3.486, 95% CI: 1.184-10.265), 90-day mortality (2.504, 1.219-5.145), 30-day overall morbidity (1.727, 1.302-2.292), 30-day major morbidity (1.770, 1.155-2.711) and postoperative hepatic insufficiency (1.967, 1.119-3.427)., Conclusions: Preoperative prealbumin level could be used to predict postoperative morbidity and mortality for patients treated with hepatic resection for HCC., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Evidence-based decision-making is critical to optimize the benefits and mitigate futility associated with surgery for patients with malignancies. Untreated hepatocellular carcinoma (HCC) has a median survival of only 6 months. The objective was to develop and validate an individualized patient-specific tool to predict preoperatively the benefit of surgery to provide a survival benefit of at least 6 months following resection., Methods: Using an international multicenter database, patients who underwent curative-intent liver resection for HCC from 2008 to 2017 were identified. Using random assignment, two-thirds of patients were assigned to a training cohort with the remaining one-third assigned to the validation cohort. Independent predictors of postoperative death within 6 months after surgery for HCC were identified and used to construct a nomogram model with a corresponding online calculator. The predictive accuracy of the calculator was assessed using C-index and calibration curves., Results: Independent factors associated with death within 6 months of surgery included age, Child-Pugh grading, portal hypertension, alpha-fetoprotein level, tumor rupture, tumor size, tumor number and gross vascular invasion. A nomogram that incorporated these factors demonstrated excellent calibration and good performance in both the training and validation cohorts (C-indexes: 0.802 and 0.798). The nomogram also performed better than four other commonly-used HCC staging systems (C-indexes: 0.800 vs. 0.542-0.748)., Conclusions: An easy-to-use online prediction calculator was able to identify patients at highest risk of death within 6 months of surgery for HCC. The proposed online calculator may help guide surgical decision-making to avoid futile surgery for patients with HCC.