Staging System For Hepatocellular Carcinoma Research Articles

Limited utility of routine bone scintigraphy in the staging of patients with hepatocellular carcinoma: A cross-sectional study

Introduction and ObjectivesThe most widely used staging system for hepatocellular carcinoma (HCC) is the Barcelona Liver Clinic Cancer (BCLC) system, which considers tumor burden, performance status, and liver function. Tumor burden is assessed with cross sectional imaging of the abdomen and chest, controversy surrounds the routine use of bone scintigraphy (BS) for detecting extrahepatic metastases. This study evaluated the role of BS in staging HCC in Mexican patients. Patients and MethodsRetrospective cross-sectional study of all adults with HCC at a Mexican referral center from 2000 to 2018. Staging included abdominal computed tomography (CT) or magnetic resonance imaging, chest CT, and BS. The main outcome was the impact of BS on staging and/or therapy plans. ResultsAmong 238 patients, 2 with fibrolamellar variant and 44 with incomplete data were excluded. Median age was 66 years, 84 % had cirrhosis, and the predominant etiology was hepatitis C virus (43 %). BCLC stages were distributed as follows: A (14 %), B (7 %), C (68 %), and D (11 %). Extrahepatic disease was present in 18 %; only 8 % patients had a positive BS. Among the positive cases, 4 were true positives, but they did not alter staging or therapy plans. ConclusionsRoutine BS in HCC staging demonstrated low yield, with a notable rate of false positives. Considering the implications of extrahepatic disease, BS may be justified for liver transplant candidates outside conventional criteria. Our study highlights the limited role of BS in early-stage HCC and advocates for a more selective utilization.

Systemic Inflammation-Based Staging System for Hepatocellular Carcinoma After Drug-Eluting Beads Transarterial Chemoembolization: A Multicenter Study

The optimal prognostic assessment for patients with hepatocellular carcinoma (HCC) after drug-eluting bead transarterial chemoembolization (DEB-TACE) remains unclear. This study aimed to propose a novel staging system in comparison with the current staging systems for HCC following DEB-TACE. From four centers, patients with HCC undergoing DEB-TACE as the initial therapy were retrospectively included and classified into training and validation sets. Multivariable regression was used to determine the independent prognostic factors in the training set. A novel staging system incorporating the independent factors was proposed and externally validated in terms of discrimination and calibration compared to other staging systems in both sets. The training and validation sets included 335 and 99 patients, respectively. Multivariable regression revealed independent factors including alpha-fetoprotein level, aspartate aminotransferase to lymphocyte count ratio index, maximum tumor diameter, Child-Pugh class, and portal vein invasion. The novel prognostic staging system, named PADCA, was proposed and outperformed other staging systems with the highest C-index, area under the curve, Wald test value, clinical benefit, and the lowest Akaike information criterion in the training and validation sets. The PADCA staging system has a superior prognostic predictive ability compared to the current staging systems. PADCA can assist clinicians in screening out the patients most likely to derive benefit from DEB-TACE and guiding the formulation of therapy and follow-up strategy.

A Simple Prognostic Scoring System for Hepatocellular Carcinoma Treated with DEB-TACE.

To develop a simple and effective prognostic scoring system to predict the efficacy of drug-eluting bead-transcatheter arterial chemoembolization (DEB-TACE) in the treatment of hepatocellular carcinoma (HCC). Data were retrospectively collected from 230 patients with HCC who received DEB-TACE treatment at six medical centers between January 2019 and December 2022. We developed a predictive score based on independent risk factors for overall survival (OS), validated the model using a validation cohort, and compared its prognostic accuracy with commonly used HCC staging systems. The number of tumors, albumin-bilirubin levels, alpha-fetoprotein levels, and portal vein thrombus grade were identified as independent factors influencing OS. Based on these factors, we established the DEB-TACE treatment of HCC (DTH) scoring system. The DTH score correlated well with OS, which decreased as the DTH score increased. According to the DTH score, patients were categorized into three risk groups: low-risk (DTH-A, 0-4 points), medium-risk (DTH-B, 5-6 points), and high-risk (DTH-A, 7 points). The OS of each risk group was 18.73±0.62 months, 12.73±0.10 months, and 6.93±0.19 months, respectively (p<0.001). The external cohort validation confirmed the accuracy of the DTH score, demonstrating superior predictive performance compared to other commonly used HCC scoring systems. The DTH-HCC scoring system effectively predicts the outcomes of HCC patients undergoing DEB-TACE as initial treatment. This model can aid in the initial planning and decision-making process for DEB-TACE treatment in HCC patients.

Treatment and prognosis study of spontaneous rupture hemorrhage in hepatocellular carcinoma: Recommendations for adding the A1 stage to the BCLC staging system.

The Barcelona Clinic Liver Cancer (BCLC) staging system is an internationally recognized clinical staging system for hepatocellular carcinoma (HCC). However, this staging system does not address the staging and surgical treatment strategies for patients with spontaneous rupture hemorrhage in HCC. In this study, we aimed to investigate the prognosis of patients with BCLC stage A undergoing liver resection for HCC with spontaneous rupture hemorrhage and compare it with the prognosis of patients with BCLC stage A undergoing liver resection without rupture. Clinical data of 99 patients with HCC who underwent curative liver resection surgery were rigorously followed up and treated at Shandong Provincial Hospital from January 2013 to January 2023. A retrospective cohort study design was used to determine whether the presence of ruptured HCC (rHCC) is a risk factor for recurrence and survival after curative liver resection for HCC. Prognostic comparisons were made between patients with ruptured and non-ruptured BCLC stage A HCC (rHCC and nrHCC, respectively) who underwent curative liver resection. rHCC (hazard ratio [HR] = 2.974, [p] = 0.016) and tumor diameter greater than 5 cm (HR = 2.819, p = 0.022) were identified as independent risk factors for overall survival (OS) after curative resection of BCLC stage A HCC. The postoperative OS of the spontaneous rupture in the HCC group (Group I) was shorter than that in the BCLC stage A group (Group II) (p = 0.008). Tumor invasion without penetration of the capsule was determined to be an independent risk factor for recurrence-free survival (RFS) after liver resection for HCC (HR = 2.584, p = 0.002). HCC with concurrent spontaneous rupture hemorrhage is an independent risk factor for postoperative OS after liver resection. TheBCLC stage A1 should be added to complement the current BCLC staging system to provide further guidance for the treatment of patients with spontaneous rupture of HCC.

Construction and Validation of a Novel Nomogram Predicting Recurrence in Alpha-Fetoprotein-Negative Hepatocellular Carcinoma Post-Surgery Using an Innovative Liver Function-Nutrition-Inflammation-Immune (LFNII) Score: A Bicentric Investigation.

We developed a nomogram based on the liver function, nutrition, inflammation, and immunity (LFNII) score to predict recurrence-free survival (RFS) post-resection in patients with hepatocellular carcinoma (HCC) exhibiting alpha-fetoprotein (AFP) negativity (AFP ≤20 ng/mL). Clinical data of 661 patients diagnosed with alpha-fetoprotein-negative hepatocellular carcinoma (AFP-NHCC) who underwent surgical resection at two medical centers between 2012 and 2021 were collected. A total of 462 and 199 patients served as the training and validation sets, respectively. Pre-operative blood markers were collected and analyzed for LFNII. The LFNII score was formulated using the least absolute shrinkage and selection operator Cox regression model. A nomogram model was developed using the training set to incorporate other relevant clinicopathological indicators and predict postoperative recurrence. Model discrimination was assessed using the receiver operating characteristic curve, calibration was evaluated using a calibration curve, and clinical applicability was assessed using clinical decision curve analysis. A comparison with liver cancer staging was performed using the nomogram model. Finally, a cohort study was conducted to validate our findings. We derived the LFNII scores from nine indicators. Elevated LFNII scores correlated with unfavorable clinicopathological features. The LFNII score area under the curve revealed superior predictive efficacy at 1-, 2-, and 5-year RFS intervals, with values of 0.675, 0.658, and 0.633, respectively. Multivariate Cox analysis revealed that a high LFNII score independently increased RFS risk in patients with AFP-NHCC. The C-index of the LFNII-nomogram model was 0.686 (95% confidence interval [CI], 0.651-0.721). The nomogram model's clinical application value surpassed that of standard HCC staging systems. The LFNII score-derived nomogram effectively predicted the RFS of patients with AFP-NHCC after curative resection.

Novel nomograms based on microvascular invasion grade for early-stage hepatocellular carcinoma after curative hepatectomy

Microvascular invasion (MVI) is a critical risk factor for postoperative recurrence of hepatocellular carcinoma (HCC). This study aimed to firstly develop and validate nomograms based on MVI grade for predicting recurrence, especially early recurrence, and overall survival in patients with early-stage HCC after curative resection. We retrospectively reviewed the data of patients with early-stage HCC who underwent curative hepatectomy in the First Affiliated Hospital of Fujian Medical University (FHFU) and Mengchao Hepatobiliary Hospital of Fujian Medical University (MHH). Kaplan–Meier curves and Cox proportional hazards regression models were used to analyse disease-free survival (DFS) and overall survival (OS). Nomogram models were constructed on the datasets from the 70% samples of and FHFU, which were validated using bootstrap resampling with 30% samples as internal validation and data of patients from MHH as external validation. A total of 703 patients with early-stage HCC were included to create a nomogram for predicting recurrence or metastasis (DFS nomogram) and a nomogram for predicting survival (OS nomogram). The concordance indexes and calibration curves in the training and validation cohorts showed optimal agreement between the predicted and observed DFS and OS rates. The predictive accuracy was significantly better than that of the classic HCC staging systems.

Optimizing hepatocellular carcinoma disease staging systems by incorporating tumor micronecrosis: A multi-institutional retrospective study

Tumor micronecrosis is a pathological feature that reflects malignant biological behavior in hepatocellular carcinoma (HCC). However, whether micronecrosis can optimize HCC staging systems remains unilluminated. A total of 1632 HCC patients who underwent curative hepatectomy in four institutions from January 2014 to December 2021 were enrolled in this study. Independent prognostic factors were identified, and optimized staging models were established using a training cohort (n = 934). The performance of optimized staging models was validated using an external cohort consisting of cases from three other institutions (n = 232). In addition, patients from our prospectively collected database (n = 379) tested the application effectiveness of the models. Harrel's c-statistics and the corrected Akaike information criterion (AICc) were used to assess the performance of staging models. In most of Barcelona Clinic Liver Cancer (BCLC) and tumor (T) stages, HCC patients with tumor micronecrosis showed poorer prognosis than those without. Tumor micronecrosis, microvascular invasion, multiple tumors and tumor size >2 cm were independent prognostic-related factors. The BCLC and T staging models incorporating tumor micronecrosis showed better performance than the original systems (c-statistic, 0.712 and 0.711 vs. 0.664 and 0.679; AICc, 2314.8 and 2322.3 vs. 2338.2 and 2338.1; respectively). Furthermore, the external validation cohort confirmed that the optimized staging models had improved efficiency compared with the original ones. Moreover, the prospective cohort demonstrated the applicability of the optimized staging systems. Tumor micronecrosis plays a stage-ascending role in HCC patients. The BCLC and T staging systems incorporating tumor micronecrosis can improve the prognosis stratification efficiency of patients.

Novel predictive nomograms based on aspartate aminotransferase‑to‑platelet ratio index for hepatocellular carcinoma with post‑operative adjuvant transarterial chemoembolization.

The clinical significance of systemic inflammation assessed with laboratory analysis of blood samples has been validated in a variety of cancers. The present study was conducted to investigate prognostic significance of preoperative aspartate aminotransferase-to-platelet ratio index (APRI) for the outcome of hepatocellular carcinoma (HCC) patients receiving post-operative adjuvant transarterial chemoembolization (PATACE). A total of 201 patients who underwent PATACE were retrospectively analyzed. A nomogram for HCC was developed using predictors based on multivariate Cox models, and bootstrapping was performed for validation. According to the ROC curve, which was used to divide patients into two cohorts: High APRI group (APRI>1.02) and Low APRI group (APRI≤1.02). In subgroup survival analysis, patients with a relatively low APRI had significantly longer disease-free survival (DFS) and overall survival (OS) than patients with a relatively high APRI, regardless of Barcelona Clinic Liver Cancer (BCLC) stages (BCLC 0/A or BCLC B/C, both P<0.05); while in China liver cancer staging I/II and TNM I/II stage patients, relatively low APRI was associated with improved DFS and OS (both P<0.05). Multivariate Cox models demonstrated that APRI and BCLC stages were independent prognostic factors of DFS and OS (both P<0.05). Nomograms for DFS and OS were constructed, respectively. Calibration curve analysis showed that the standard curve fitted well with the predicted curve. Time-receiver operating characteristic curve analysis revealed that the nomogram had high efficiency. Decision curve analysis demonstrated the high clinical value of the nomogram. APRI is an independent prognostic factor of DFS and OS in HCC patients receiving PATACE, and the combination of APRI with the HCC staging system can refine risk stratification to provide a more accurate prognostic assessment for the outcome of patients receiving PATACE.

Understanding the role of radiologists in complex treatment decisions for patients with hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver and represents a significant global health burden. Management of HCC can be challenging due to multiple factors, including variable expectations for treatment outcomes. Several treatment options are available, each with specific eligibility and ineligibility criteria, and are provided by a multidisciplinary team of specialists. Radiologists should be aware of the types of treatment options available, as well as the criteria guiding the development of individualized treatment plans. This awareness enables radiologists to contribute effectively to patient-centered multidisciplinary tumor boards for HCC and play a central role in reassessing care plans when the treatment response is deemed inadequate. This comprehensive review aims to equip radiologists with an overview of HCC staging systems, treatment options, and eligibility criteria. The review also discusses the significance of imaging in HCC diagnosis, treatment planning, and monitoring treatment response. Furthermore, we highlight the crucial branch points in the treatment decision-making process that depend on radiological interpretation.

Prognostic factors and survival prediction in hepatocellular carcinoma: development and validation of a novel nomogram based on the SEER database.

Current staging systems for hepatocellular carcinoma (HCC) still have limitations in clinical practice. Our study aimed to explore the prognostic factors and develop a new nomogram to predict the cancer-specific survival (CSS) for patients with HCC. A total of 6,166 HCC patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were randomly grouped into the training cohort (70%) and validation cohort (30%). Multivariate Cox analysis was used to identify prognostics factors for CSS of patients, then we incorporated these variables and presented a new nomogram to predict 2- and 5-year CSS. The performance of the nomogram was assessed with respect to its calibration, concordance index (C-index), area under the receiver operating characteristic (ROC) curve (AUC), and decision curve analysis (DCA). Multivariate Cox analysis revealed that American Joint Committee on Cancer (AJCC) stage, race, grade, surgery, chemotherapy, radiation, tumor size, bone metastasis (BM), and alpha-fetoprotein (AFP) were independently associated with CSS. The prediction nomogram which contained these predictors showed good performance, with a C-index of 0.802 [95% confidence interval (CI), 0.792-0.812] in the training cohort and 0.801 (95% CI, 0.787-0.815) in the validation cohort. The calibration curves demonstrated good agreement between the actual observation and the nomogram prediction. Furthermore, the nomogram showed improved discriminative capacity (AUC, 0.873 and 0.875 for 2- and 5-year CSS in validation set) compared to the 7th tumor-node-metastasis (TNM) staging system (AUC, 0.735 and 0.717). The DCA also indicated good application of the nomogram. This study presents a novel nomogram that incorporates the important prognostic factors of HCC, which can be conveniently used to accurately predict the 2- and 5-year CSS of patients with HCC, thus assisting individualized clinical decision making.

Novel online calculator to predict reduced risk of early recurrence from adjuvant transarterial chemoembolisation for patients with hepatocellular carcinoma

BackgroundThe role of adjuvant transarterial chemoembolisation (TACE) to reduce postoperative recurrence varies widely among patients undergoing hepatectomy with curative intent for hepatocellular carcinoma (HCC). Personalised predictive tool to select which...

Analysis of Alfa-Fetoprotein as A Staging Determiner of Hepatocellular Carcinoma Progresivity

Hepatocellular carcinoma (HCC) is the most common malignant tumor with a poor prognosis and is known as the silent killer. The currently recommended HCC staging system is Barcelona Clinic Liver Cancer (BCLC). The Alpha-fetoprotein (AFP) test is still used to manage HCC patients. The purpose was to find out the AFP comparations and to decide cut-off values for each stage according to BCLC. Cross-sectional retrospective study using secondary data from medical records of Outpatients Clinic and Inpatients from January 2016 to October 2021 at Dr. Wahidin Sudirohusodo Hospital. A total of 432 samples based on BCLC were taken with AFP values and analyzed in this study. The male sample was 72.7%. The highest age is 46-65 years (62.7%). The etiology of HCC mostly is hepatitis B (72.5%). The most BCLC systems were BCLC B (53.7%), followed by BCLC A (25.9%), BCLC D (12.5%), and BCLC C (7.87%). There was a significant difference in AFP values between BCLC stages and the highest significance was BCLC D, followed by BCLC C, B, and A (p=0.05). The cut-off results values at the BCLC stage were BCLC A &lt;21.84 ng/mL, BCLC B: 21.84 ng/mL (sensitivity 90.3%, specificity 85.7%), BCLC C: 478 ng/mL (sensitivity and specificity 100%), BCLC D: 7.693 ng/mL (sensitivity and specificity 100%). There was a significant difference in AFP values between BCLC stages and the highest is BCLC D. Based on the results of calculating the cut-off value, which has good sensitivity and specificity, AFP can be used as a determinant of stage progression of HCC.

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

BackgroundA preoperative predictive score for hepatocellular carcinoma (HCC) can help stratify patients who undergo resection relative to long-term outcomes and tailor treatment strategies. MethodsPatients 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. ResultsAmong 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/). DiscussionThe online mFIBA calculator may help surgeons with clinical decision-making to individualize perioperative treatment strategies for patients undergoing resection of HCC.

Inflammation-related nomogram for predicting survival of patients with unresectable hepatocellular carcinoma received conversion therapy

The efficacy of conversion therapy for patients with unresectable hepatocellular carcinoma (HCC) is a common clinical concern.To analyse the prognostic factors of overall survival (OS) in patients with unresectable HCC who received conversion therapy.One hundred and fifty patients who met the inclusion criteria were enrolled and divided into a training cohort (n = 120) and a validation cohort (n = 30). Using the independent risk factors in the training cohort, a nomogram model was constructed to predict OS for patients treated with transarterial chemoembolization following hepatic resection. The nomogram was internally validated with the bootstrapping method. The predictive performance of nomogram was assessed by Harrell's concordance index (C-index), calibration plot and time-dependent receiver operating characteristic curves and compared with six other conventional HCC staging systems.Multivariate Cox analysis identified that albumin, blood urea nitrogen, gamma-glutamyl transpeptidase to platelet ratio, platelet to lymphocyte ratio, macrovascular invasion and tumour number were the six independent prognostic factors correlated with OS in nomogram model. The C-index in the training cohort and validation cohort were 0.752 and 0.807 for predicting OS, which were higher than those of the six conventional HCC staging systems (0.563 to 0.715 for the training cohort and 0.458 to 0.571 for the validation cohort). The calibration plots showed good consistency between the nomogram prediction of OS and the actual observations of OS. Decision curve analyses indicated satisfactory clinical utility. With a total nomogram score of 196, patients were accurately classified into low-risk and high-risk groups. Furthermore, we have deployed the model into online calculators that can be accessed for free at https://ctmodelforunresectablehcc.shinyapps.io/DynNomapp/.The nomogram achieved optimal individualized prognostication of OS in HCC patients who received conversion therapy, which could be a useful clinical tool to help guide postoperative personalized interventions and prognosis judgement.

Overall survival among patients who undergo resection does not differ significantly between T1a and T1b hepatocellular carcinoma based on the 8th American Joint Commission on Cancer.

The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for hepatocellular carcinoma (HCC) has been used since 2018. However, whether any significant difference in overall survival (OS) exists between patients with T1a and T1b HCC who undergo resection has been controversial. We aim to clarify this issue. We consecutively enrolled newly diagnosed HCC patients who underwent liver resection (LR) from 2010 to 2020 at our institution. OS was estimated using the Kaplan-Meier method and compared using log-rank tests. Prognostic factors for OS were identified by multivariate analysis. This study enrolled 1250 newly diagnosed HCC patients who underwent LR. No significant differences in OS were identified between patients with T1a and T1b tumors among all patients (p = 0.694), cirrhotic patients (p = 0.753), non-cirrhotic patients (p = 0.146), patients with alpha-fetoprotein (AFP) > 20ng/ml (p = 0.562), patients with AFP ≤ 20ng/ml (p = 0.967), patients with Edmondson grade 1 or 2 (p = 0.615), patients with Edmondson grade 3 or 4 (p = 0.825), patients positive for hepatitis B surface antigen (HBsAg; p = 0.308), in patients positive for anti-hepatitis C virus (HCV) antibody (p = 0.781), or patients negative for both HBsAg and anti-HCV antibody (p = 0.125). Using T1a as the reference, multivariate analysis showed that T1b is not a significant predictive factor for OS (hazard ratio (HR): 1.338; 95% confidence interval (CI):0.737-2.431; p = 0.339). No significant difference in OS was observed between patients who underwent LR to treat T1a and T1b HCC tumors.

Does size matter for resection of giant versus non-giant hepatocellular carcinoma? A meta-analysis.

Research on long-term survival after resection of giant (≥ 10 cm) and non-giant hepatocellular carcinoma (HCC) (< 10 cm) has produced conflicting results. This study aimed to investigate whether oncological outcomes and safety profiles of resection differ between giant and non-giant HCC. PubMed, MEDLINE, EMBASE, and Cochrane databases were searched. Studies designed to investigate the outcomes of giant vs non-giant HCC were included. The primary endpoints were overall survival (OS) and disease-free survival (DFS). The secondary endpoints were postoperative complications and mortality rates. All studies were assessed for bias using the Newcastle-Ottawa Scale. 24 retrospective cohort studies involving 23747 patients (giant = 3326; non-giant = 20421) who underwent HCC resection were included. OS was reported in 24 studies, DFS in 17 studies, 30-d mortality rate in 18 studies, postoperative complications in 15 studies, and post-hepatectomy liver failure (PHLF) in six studies. The HR was significantly lower for non-giant HCC in both OS (HR 0.53, 95%CI: 0.50-0.55, P < 0.001) and DFS (HR 0.62, 95%CI: 0.58-0.84, P < 0.001). No significant difference was found for 30-d mortality rate (OR 0.73, 95%CI: 0.50-1.08, P = 0.116), postoperative complications (OR 0.81, 95%CI: 0.62-1.06, P = 0.140), and PHLF (OR 0.81, 95%CI: 0.62-1.06, P = 0.140). Resection of giant HCC is associated with poorer long-term outcomes. The safety profile of resection was similar in both groups; however, this may have been confounded by reporting bias. HCC staging systems should account for the size differences.

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

BackgroundThis 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). MethodsPatients 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. ResultsA 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. DiscussionThe PreopScore can be used as a better guide to preoperatively identify patients and individualize pre-/post-operative strategies.

Prognostic nomograms for HBV-related BCLC 0-a stage hepatocellular carcinoma incorporating aspartate aminotransferase to albumin ratio

Background Curative hepatectomy is currently the first-line treatment for hepatocellular carcinoma (HCC), but the prognosis is still not optimistic. The prediction model for prognosis of hepatitis B virus (HBV)-related BCLC 0-A stage HCC has not been well established. Therefore, we aimed to develop new nomograms to predict recurrence and survival in these patients. Methods A total of 982 patients with HBV-related BCLC 0-A stage HCC who underwent curative hepatectomy at West China Hospital from February 2007 to February 2016 were retrospectively collected and randomly allocated to a training set and a validation set in a ratio of 4:1. Prognostic nomograms using data from the training set were developed using a Cox regression model and validated on the validation set. Results We constructed nomograms based on independent factors for recurrence-free survival (RFS) (tumor size, satellite, microvascular invasion, capsular invasion, differentiation and aspartate aminotransferase to albumin ratio (ASAR)) and overall survival (OS) (gender, tumor size, satellite, microvascular invasion, differentiation, lymphocyte count, and ASAR). Compared with conventional HCC staging systems and other nomograms reported by previous literature, our ASAR integrated nomograms predicted RFS and OS with the highest C-indexes (0.682 (95%CI: 0.646–0.709), 0.729 (95%CI: 0.691–0.766), respectively) and had well-fitted calibration curves in the training set. Concurrently, the nomograms also obtained consistent results in the validation set. DCA revealed that our nomograms provided the largest clinical net benefits. Conclusion We first constructed ASAR integrated nomograms to predict the prognosis of HBV-related BCLC 0-A stage HCC patients after curative hepatectomy with good performance.

Development and Validation of Prognostic Nomograms for Hepatocellular Carcinoma After Hepatectomy Based on Inflammatory Markers.

The value of lactate dehydrogenase (LDH) compared with other inflammation-based scores in predicting the outcomes of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients after curative resection remains unknown. This study aims to evaluate the predictive value of LDH and develop novel nomograms to predict postoperative recurrence and survival in these patients. This study retrospectively collected 1560 patients with HBV-related HCC who underwent curative resection from four institutions in China. In total, 924 patients were recruited from our center and randomly divided into the training cohort (n = 616) and internal validation (n = 308) cohorts. Additionally, 636 patients were selected from three other centers as the external validation cohort. The C index of inflammation-based scores was calculated and compared in the training cohort. Novel models were developed according to multivariable Cox regression analysis in the training cohort and validated in the internal and external validation cohorts. LDH showed a higher C-index than other inflammation-based scores for recurrence survival (RFS, 0.60, 95% CI, 0.58-0.61) and overall survival (OS, 0.65, 95% CI, 0.63-0.68). The nomograms of RFS and OS were developed based on tumor diameter, macrovascular invasion, AFP, operative hemorrhage, tumor differentiation, tumor number and LDH and achieved a high C-index (0.78, 95% CI, 0.76-0.79 and 0.81, 95% CI, 0.79-0.83), which were remarkably higher than the C-indexes of the five conventional HCC staging systems (0.52-0.62 for RFS and 0.53-0.67 for OS). The nomograms were validated in the internal validation cohort (0.77 for RFS, 0.78 for OS) and external validation cohort (0.80 for RFS, 0.81 for OS) and performed well-fitted calibration curves. The two nomograms based on inflammatory markers achieved optimal prediction for RFS and OS of patients with HBV-related HCC after hepatectomy.

A proposal for T1 subclassification in hepatocellular carcinoma: reappraisal of the AJCC 8th edition

BackgroundIn the 8th edition of American Joint Committee on Cancer (AJCC) staging system for hepatocellular carcinoma (HCC), tumor size is not considered in T1 stage. The present study aimed to find out the optimal cutoff for tumor size to further stratify patients with T1 HCC.MethodsOperated HCC patients were identified from the Chang Gung Research Database (CGRD), and the patients with T1bN0M0 tumors were further divided into two groups based on the tumor size. The resulting subgroups were denoted as T1b (≤ cutoff) and T1c (> cutoff). The survivals were compared between T1a/b and T1c as well as T1c and T2.ResultsFrom 2002 to 2018, a total of 2893 patients who underwent surgery for T1N0M0 HCC were identified from the CGRD. After excluding cases who died within 30 days of surgery, Kaplan–Meier survival analysis discovered that T1 tumors > 65 mm (T1c) had survivals similar to those of T2N0M0 tumors. Cox regression multivariate analysis further demonstrated that tumor size > 6.5 cm was an independent poor prognostic indicator for T1 HCC. Sensitivity tests also confirmed that tumors lager than 6.5 cm were significantly more likely to develop both tumor recurrence and liver-specific death after surgery.ConclusionsOur study demonstrated that tumor size would significantly impact the survival outcome of T1 HCC after surgery. Due to significantly worse survival, we proposed a subclassification within T1 HCC, T1c: solitary tumor > 6.5 cm without vascular invasion, to further stratify those patients at risk. Further studies are mandatory to validate our findings.