Surgical resection versus transarterial chemoembolization for patients with hepatocellular carcinoma beyond Milan criteria: prognostic role of tumor burden score.

Tumor burden score (TBS) has been recently introduced to indicate the extent of tumor burden in different cancers, but its role in advanced hepatocellular carcinoma (HCC) is unclear. We aimed to determine the prognostic role of TBS in patients with HCC beyond the Milan criteria receiving surgical resection (SR) or transarterial chemoembolization (TACE). A total of 1303 newly diagnosed HCC patients beyond Milan criteria receiving SR or TACE as the primary therapy were retrospectively analyzed. Independent prognostic predictors were examined by the multivariate Cox proportional hazards model. SR was associated with better overall survival compared with TACE in these patients. Multivariate Cox analysis of the entire cohort revealed that age > 66 years (hazard ratio [HR]: 1.145, 95% confidence interval [CI]: 1.004-1.305, p = 0.043), serum α-fetoprotein > 200 ng/mL (HR: 1.602, 95% CI: 1.402-1.831, p < 0.001), performance status 2-4 (HR: 1.316, 95% CI: 1.115-1.553, p < 0.001), medium TBS (HR: 1.225, 95% CI:1.045-1.436, p = 0.012), high TBS (HR: 1.976, 95% CI: 1.637-2.384, p < 0.001), albumin-bilirubin (ALBI) grade 2-3 (HR: 1.529, 95% CI: 1.342-1.743, p < 0.001), presence of vascular invasion (HR: 1.568, 95% CI: 1.354-1.816, p < 0.001), and TACE (HR: 2.396, 95% CI: 2.082-2.759, p < 0.001) were linked with decreased survival. SR consistently predicted a significantly better survival in different TBS subgroups. TBS is a feasible and independent prognostic predictor in HCC beyond the Milan criteria. SR provides better long-term outcome compared with TACE in these patients independent of TBS grade, and should be considered as the primary treatment modality in this special patient group.

Surgical strategy for colorectal cancer with synchronous liver and extrahepatic metastases: A scoring system and decision tree model.

BACKGROUND: The role of hepatectomy in a specific group of patients with synchronous colorectal cancer with liver metastases (SCRLM) and synchronous extrahepatic disease (SEHD) is still unclear. The aim of this study was to evaluate the efficacy of liver surgery and define the selection criteria for surgical candidates in patients with SCRLM + SEHD. METHODS: Between July 2007 and October 2018, 475 patients with colorectal cancer with liver metastases (CRLM) who underwent liver resection were retrospectively reviewed. Sixty-five patients with SCRLM + SEHD were identified and included in the study. Clinical pathological data of these patients were analyzed to evaluate the influence on survival. Important prognostic factors were identified by univariate and multivariate analyses. The risk score system and decision tree analysis were generated according to the important prognostic factors for better patient selection. RESULTS: The 5-year survival rate of patients with SCRLM + SEHD was 21.9%. The most important prognostic factors were SCRLM number of more than five, site of SEHD other than the lung only, inability to achieve SCRLM + SEHD R0 resection, and BRAF mutation of cancer cells. The proposed risk score system and decision tree model easily discriminated between patients with different survival rates and identified the profile of suitable surgical patients. CONCLUSION: Liver surgery should not be a contraindication for patients with SCRLM + SEHD. Patients with complete SCRLM + SEHD R0 resection, SCRLM number less than or equal to five, SEHD confined to the lung only, and wild-type BRAF could have favorable survival outcomes. The proposed scoring system and decision tree model may be beneficial to patient selection in clinical use.

Long-term outcomes of liver transplantation for alcohol-related liver disease.

BACKGROUND: Liver transplantation (LT) is being increasingly performed for alcohol-related liver disease (ALD). It is unclear whether the increasing frequency of LTs in ALD patients has a negative impact on deceased-donor (DDLT) allocation and whether the current policy of 6 months of abstinence before transplantation effectively prevents recidivism after transplantation or improves long-term outcomes. METHODS: A total of 506 adult LT recipients, including 97 ALD patients, were enrolled. The outcomes of ALD patients were compared with those of non-ALD patients. The 97 ALD patients were further divided into group A (6-month abstinence) and group N (nonabstinence) based on the pretransplant alcohol withdrawal period. The incidence of relapsed drinking and the long-term outcomes were compared between the two groups. RESULTS: The prevalence of LT for ALD significantly increased after 2016 (27.0% vs 14.0%; p < 0.01), but the frequency of DDLT for ALD remained unchanged (22.6% vs 34.1%, p = 0.210). After a median follow-up of 56.9 months, patient survival was comparable between the ALD and non-ALD patients (1, 3, and 5 years posttransplant: 87.6%, 84.3%, and 79.5% vs 82.8%, 76.6%, and 72.2%, respectively; p = 0.396). The results were consistent irrespective of the transplant type and disease severity. In ALD patients, 22 of the 70 (31.4%) patients reported relapsed drinking after transplantation, and the prevalence in group A had a higher tendency than that in group N (38.3% vs 17.4%, p = 0.077). Six months of abstinence or nonabstinence did not result in a survival difference, and de novo malignancies were the leading cause of late patient death in ALD patients. CONCLUSION: LT achieves favorable outcomes for ALD patients. Six months of abstinence pretransplant did not predict the risk of recidivism after transplantation. The high incidence of de novo malignancies in these patients warrants a more comprehensive physical evaluation and better lifestyle modifications to improve long-term outcomes.

Dual hepatitis B and C-associated hepatocellular carcinoma: clinical characteristics, outcome, and prognostic role of albumin-bilirubin grade.

BACKGROUND: Albumin-bilirubin (ALBI) grade is used to evaluate the outcome of patients with hepatocellular carcinoma (HCC) which is often associated with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. This study aimed to investigate the clinical characteristics, outcome, and prognostic role of ALBI grade in dual HBV/HCV-related HCC. METHODS: A total 3341 HCC patients with viral etiology were prospectively enrolled and retrospectively analyzed. Multivariate Cox proportional hazards model was used to identify independent prognostic predictors. RESULTS: Of all patients, 2083 (62%), 1068 (32%), and 190 (6%) patients had HBV, HCV, and dual HBV/HCV infection, respectively. The mean age of HBV, HCV, and dual virus group was 60, 68, and 64 years (p < 0.001), respectively. There was no significant survival difference between HBV, HCV, and dual HBV/HCV-related HCC group (p = 0.712). Multivariate Cox analysis in dual HBV/HCV-related HCC showed that multiple tumors [hazard ratio (HR): 1.537, p = 0.044], tumor size >3 cm (HR 2.014, p = 0.044), total tumor volume (TTV) >50 cm3 (HR 3.050, p < 0.001), vascular invasion (HR 3.258, p < 0.001), performance status 2-4 (HR 2.232, p < 0.001), ALBI grade 2-3 (HR 2.177, p < 0.001), and BCLC stage B-D (HR 2.479, p < 0.001) were independent predictors of poor survival. CONCLUSIONS: Dual viral infection does not accelerate the development of HCC in HBV carriers. Patient survival is similar between dual HBV/HCV-related HCC and single HBV- or HCV-related HCC group. The ALBI grade is a robust prognostic model in dual virus-related HCC to discriminate patient long-term survival.

Repeated loco-regional therapies for hepatocellular carcinoma is associated with inferior outcome after living donor liver transplantation in cirrhotic patients.

BACKGROUND: Liver transplantation is the definitive treatment for defined stage hepatocellular carcinoma (HCC) in cirrhotic patients. Loco-regional therapy (LRT) may be considered before transplantation to prevent the disease progression and the patient from dropping out of the waiting list. This study aims to evaluate the impact of repeated pretransplant LRTs on the long-term outcomes in HCC liver transplant recipients. METHODS: Between 2004 and 2019, living donor liver transplantation (LDLT) recipients with viable HCC on the explant livers were enrolled. Uni- and multivariate analysis was performed with the Cox regression model to stratify the risk factors associated with HCC recurrence and patent survival after LDLT. RESULTS: A total of 124 patients were enrolled, in which 65.3% (n = 81) were Barcelona Clinic Liver Cancer classification stage B or D and 89% (n = 110) had advanced fibrosis or cirrhosis on the explanted livers. After a median follow-up of 41 months (IQR: 24-86.5), there were 18 cases (13.7%) of HCC recurrence. Univariate analysis showed that the model of end-stage liver disease and Child-Turcotte-Pugh score, pretransplant alpha-fetoprotein value (>500 ng/ml), repeated pretransplant LRTs (N > 4), increased tumor numbers and maximal size, presence of microvascular invasion, and the histological grading of the tumors are risk factors of inferior outcomes. In multivariate analysis, only repeated pretransplant LRTs (N > 4) had a significant impact on both the overall- and recurrence-free survival. The impact of pretransplant LRT was consistently significant among subgroups based on their LRT episodes (N = 0, 1-4, >4 respectively). CONCLUSION: Repeated LRT for HCC can be associated with the risk of tumor recurrence and inferior patient survival after LDLT in cirrhotic patients. Early referral of those eligible for transplantation may improve the treatment outcomes in these patients.

Comparable benefits of HCV eradication by direct acting antivirals and interferon-based therapy in patients with hepatocellular carcinoma undergoing surgical resection.

Whether direct-acting antivirals (DAA) provide comparable survival benefit with interferon (IFN)-based therapy remains unclear. The aim of this study was to compare the outcomes after achieving SVR by IFN-based and DAA therapy after resection of HCV-related hepatocellular carcinoma (HCC). Consecutive 285 patients receiving curative resection for HCV-related HCC were retrospectively enrolled, including 103 (36.1%) and 69 (24.2%) patients with IFN-based and DAA therapy, respectively. Factors associated with recurrence, overall survival (OS) and hepatic decompensation-free survival were evaluated. The SVR rate of DAA was 95.7% in HCC patients. During a median follow-up period of 49.6 months, 102 (35.8%) patients died and 63 (24%) developed hepatic decompensation. By multivariate analysis, SVR by DAA or IFN-based therapy was not associated with early or late HCC recurrence. Achieving SVR (by IFN-based therapy: HR=0.321, P<0.001; by DAA: HR=0.396, P=0.011), BCLC stage B-C (HR=1.914, P=0.024), FIB-4 score >3.25 (HR=1.664, P=0.016) and microvascular invasion (HR=1.603, P=0.048) were independent predictors of OS. Achieving SVR (by IFN-based therapy: HR=0.295, P<0.001; by DAA: HR=0.193, P=0.002), BCLC stage B-C (HR=2.975, P=0.001), GGT >70 U/L (HR=1.931, P=0.015) and cirrhosis (HR=2.035, P=0.007) were independent predictors of decompensation-free survival. The benefit of achieving SVR was consistently observed in cirrhotic and non-cirrhotic patients, and in patients with and without HCC recurrence. In conclusion, achieving SVR by either DAA or IFN-based therapy provide comparable and significant reduction of mortality and hepatic decompensation after surgical resection of HCV-related HCC. DAA therapy should be prescribed for all HCC patients after curative surgical resection.

Predictors of long-term recurrence and survival after resection of HBV-related hepatocellular carcinoma: the role of HBsAg.

The recurrence rate remains high even under nucleos(t)ide analogues (NUCs) therapy in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after resection. The aim of this study is to evaluate the prognostic role of HBsAg in patients undergoing surgical resection for HBV-related HCC in NUCs era. Consecutive 522 patients undergoing surgical resection for HBV-related HCC were retrospectively enrolled. Factors associated with early (within 2 years), late (year 2 to 5), very late (beyond 5 years) recurrence and early or late mortality (within or beyond 5 years) were evaluated. During a median follow-up period of 59 months, 308 (59%), and 146 (28%) patients developed recurrence and mortality, respectively. HBsAg level did not correlate with early recurrence and mortality. By multivariate analyses, HBsAg >200 IU/mL (hazard ratio (HR)=1.778, P=0.037) and presence of cirrhosis (HR=2.157, P=0.001) were independent predictors of late recurrence, while HBsAg >50 IU/mL (HR=4.658, P=0.038), body mass index >25 kg/m2 (HR=2.720, P=0.013) and significant hepatic fibrosis (HR=2.509, P=0.039) were independent predictors of very late recurrence. HBsAg >50 IU/mL (HR=11.427, P=0.017), age >60 years (HR=2.688, P=0.006), albumin ≤3.5 g/dL (HR=4.739, P<0.001) and presence of cirrhosis (HR=2.781, P=0.006) were independent predictors of late mortality beyond 5 years. Combining these factors could well predict patients with minimal risk of long-term recurrence and mortality. In conclusion, tumor factors, liver function surrogate markers, metabolic factors and serum HBsAg levels play distinct roles in recurrence and survival at different time intervals after surgical resection for HBV-related HCC. Pre-operative HBsAg level is an important predictor of long-term recurrence and survival in patients with HBV-related HCC undergoing surgical resection.

Group-based trajectory analysis of postoperative pain and outcomes after liver cancer surgery.

BACKGROUND: Although previous studies have shown connections between pain and worse cancer outcomes, few clinical studies have evaluated their direct association, and the current study aimed to investigate the potential association between acute pain trajectories and postoperative outcomes after liver cancer surgery. METHODS: This retrospective study was conducted in a single medical center and included patients who received liver cancer surgery between January 2010 and December 2016. Maximal pain intensity was recorded daily using a numerical rating scale during the first postoperative week. Group-based trajectory analysis was performed to classify the variations in pain scores over time. Cox and linear regression analyses were used to assess the effect of pain trajectories on recurrence-free survival, overall survival, and length of hospital stay (LOS) after surgery and to explore predictors of these outcomes. RESULTS: A total of 804 patients with 5396 pain score observations were analyzed within the present study. Group-based trajectory analysis categorized the changes in postoperative pain into three groups: group 1 had constantly mild pain (76.6%), group 2 had moderate/severe pain dropping to mild (10.1%), and group 3 had mild pain rebounding to moderate (13.3%). Multivariable analysis demonstrated that on average, group 3 had a 7% increase in LOS compared with the group 1 (p = 0.02) and no significant difference in the LOS was noted between pain trajectory groups 2 and 1 (p = 0.93). Pain trajectories were not associated with recurrence-free survival or overall survival after liver cancer surgery. CONCLUSION: Acute pain trajectories were associated with LOS but not cancer recurrence and survival after liver cancer surgery. Group-based trajectory analysis provided a promising approach for investigating the complex relationships between variations in postoperative pain over time and clinical outcomes.

Effect of Primary Tumor Location on Postmetastasectomy Survival in Patients with Colorectal Cancer Liver Metastasis.

BACKGROUND: The effects of primary tumor location on colorectal liver metastasis (CRLM) and post-hepatic-metastasectomy overall survival (OS) are controversial. This study evaluated the difference in post-hepatic-metastasectomy OS among right-sided colon, left-sided colon, and rectal cancer groups. METHODS: In total, 381 patients who underwent curative-intent CRLM resection were enrolled. Patients were grouped based on the primary tumor location (right-sided, left-sided, and rectum). The Kaplan-Meier analysis and log-rank test were performed for survival analysis. The univariate and multivariate analyses of clinical and pathological factors were performed using the Cox proportional hazards model. RESULTS: Significant OS difference was noted among the three groups (log-rank, p = 0.014). The multivariate analysis revealed a 32% lower death risk in left-sided colon cancer compared with right-sided colon cancer (hazard ratio [HR] 0.68, p = 0.042), whereas no OS difference was noted between the rectal cancer and right-sided colon cancer groups. The left- versus right-sided OS advantage was noted only in the KRAS wild-type subgroup (HR 0.46, p = 0.002), and a rectal versus right-sided OS disadvantage was noted in the KRAS mutant subgroup (HR 1.78, p = 0.03). CONCLUSIONS: The CRLM post-hepatic-metastasectomy OS was superior in left-sided colon cancer than in right-sided colon cancer and was similar in rectal and right-sided colon cancer. The OS difference in different primary tumor locations is dependent on KRAS mutation status, with a decreased left- versus right-sided death risk noted only in KRAS wild-type colon cancer and an increased rectal versus right-sided death risk noted only in KRAS mutant colon cancer.

Author Correction: Evolution of etiology, presentation, management and prognostic tool in hepatocellular carcinoma.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Safe Strategy to Initiate Total Laparoscopic Donor Right Hepatectomy: A Stepwise Approach From a Laparoscopy-Assisted Method.

BACKGROUND: Total laparoscopic donor right hepatectomy (TLDRH) for adult living liver donors has been reported by a few experienced centers, but with limited cases, its safety and feasibility remain controversial. We report our experience initiating TLDRH using a stepwise approach to gradually convert laparoscopy-assisted donor right hepatectomy (LADRH) to TLDRH. METHODS: We retrospectively analyzed the data of 61 LADRHs, 56 conventional open donor right hepatectomies (CODRHs), and 3 TLDRHs performed between March 2014 and June 2018. RESULTS: There were no significant differences in perioperative outcomes between donors undergoing LADRH and CODRH, except for a slight elevations in the operative time (436.5 vs 392.9 min, p < 0.001) and the graft warm ischemic time (5.4 vs 4.0 min, p < 0.001) in the LADRH group. The recipients' posttransplant one-year survival rates in the LADRH and CODRH groups were also similar (93.2% and 94.6%, p = 0.384). For three donors in whom TLDRH was converted from LADRH in a stepwise manner, the average operative time and blood loss were 570 min and 316.7 ml, respectively. Donors were discharged on postoperative day 10 without any surgical complications. CONCLUSIONS: LADRH can be performed routinely on liver living donors. A stepwise approach could be adopted to "covert" suitable donors from LADRH to a total laparoscopic procedure to maximize donor safety. This strategy is reliable and could be reproduced in most LDLT centers.

Evolution of etiology, presentation, management and prognostic tool in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide, but its current status is unclear. We aimed to investigate the evolution of etiology, presentation, management and prognostic tool in HCC over the past 12 years. A total of 3349 newly diagnosed HCC patients were enrolled and retrospectively analyzed. The comparison of survival was performed by the Kaplan-Meier method with the log-rank test. Hepatitis B and C virus infection in HCC were continuously declining over the three time periods (2004-2007, 2008-2011, 2012-2015; p < 0.001). At diagnosis, single tumor detection rate increased to 73% (p < 0.001), whereas vascular invasion gradually decreased to 20% in 2012-2015 (p < 0.001). Early stage HCC gradually increased from 2004-2007 to 2012-2015 (p < 0.001). The probability of patients receiving curative treatment and long-term survival increased from 2004-2007 to 2012-2015 (p < 0.001). The Cancer of Liver Italian Program (CLIP) and Taipei Integrated Scoring (TIS) system were two more accurate staging systems among all. In conclusion, the clinical presentations of HCC have significantly changed over the past 12 years. Hepatitis B and C virus-associated HCC became less common, and more patients were diagnosed at early cancer stage. Patient survival increased due to early cancer detection that results in increased probability to undergo curative therapies.

Differential Survival Impact of Diabetes Mellitus on Hepatocellular Carcinoma: Role of Staging Determinants.

BACKGROUND: Diabetes mellitus (DM) is common in patients with hepatocellular carcinoma (HCC) and may impact survival. Very few studies focused on the influence of DM in different clinical scenarios. We evaluated the prognostic impact of DM on HCC patients stratified by liver dysfunction, Milan criteria, and performance status defined in the Barcelona Clínic Liver Cancer staging parameters. METHODS: A prospective dataset of 3573 HCC patients between 2002 and 2016 was retrospectively analyzed. The multivariate Cox proportional hazards model was used to identify independent prognostic predictors. The Kaplan-Meier method with a log-rank test was applied to compare the survival distributions between different patient groups. RESULTS: Among all, DM was not an independent prognostic predictor in the Cox multivariate analysis (p = 0.1044). In the subgroup analysis, DM was not a significant prognostic predictor in Child-Turcotte-Pugh class A or class B/C patients. However, DM was associated with a decreased survival in patients within the Milan criteria (hazard ratio [HR] 1.36, 95% confidence interval [CI] 1.155-1.601, p = 0.0002) and in those with the performance status 0 (HR 1.213, 95% CI 1.055-1.394, p = 0.0067) in the multivariate Cox analysis, but not in those beyond the Milan criteria and poor performance status. CONCLUSIONS: DM is highly prevalent in HCC patients and has a distinct survival impact. DM is an independent survival predictor among patients within the Milan criteria and good performance status. These high-risk patients should be closely monitored, and aggressive anticancer treatment should be considered.

Albumin-bilirubin grade-based nomogram of the BCLC system for personalized prognostic prediction in hepatocellular carcinoma.

BACKGROUND & AIMS: The prognostic accuracy of individual hepatocellular carcinoma (HCC) patient in each Barcelona Clinic Liver Cancer (BCLC) stage is unclear. We aimed to develop and validate an albumin-bilirubin (ALBI) grade-based nomogram of BCLC to estimate survival for individual HCC patient. METHODS: Between 2002 and 2016, 3690 patients with newly diagnosed HCC were prospectively enrolled and retrospectively analysed. Patients were randomly split into derivation and validation cohort by 1:1 ratio. Multivariate Cox proportional hazards model was used to generate the nomogram from tumour burden, ALBI grade and performance status (PS). The concordance index and calibration plot were determined to evaluate the performance of this nomogram. RESULTS: Beta coefficients from the Cox model were used to assign nomogram points to different degrees of tumour burden, ALBI grade and PS. The scores of the nomogram ranged from 0 to 24, and were used to predict 3- and 5-year patient survival. The concordance index of this nomogram was 0.77 (95% confidence interval [CI]: 0.71-0.81) in the derivation cohort and 0.76 (95% CI: 0.71-0.81) in the validation cohort. The calibration plots to predict both 3- and 5-year survival rate well matched with the 45-degree ideal line for both cohorts, except for ALBI-based BCLC stage 0 in the validation cohort. CONCLUSIONS: The proposed ALBI-based nomogram of BCLC system is a simple and feasible strategy in the precision medicine era. Our data indicate it is a straightforward and user-friendly prognostic tool to estimate the survival of individual HCC patient except for very early stage patients.

Radiological features and outcomes of combined hepatocellular-cholangiocarcinoma in patients undergoing surgical resection.

BACKGROUND/PURPOSE: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer. Preoperative diagnosis of cHCC-CCA is difficult, and outcome of cHCC-CCA is obscured. Our study aimed to investigate the clinicopathological and radiological features of cHCC-CCA and compare their outcomes with hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). METHODS: From August 2010 to December 2017, 891 patients undergoing liver tumor resection in Taipei Veterans General Hospital, including 30 patients with pathology-proven cHCC-CCA, 819 HCC, and 42 ICC were retrospectively reviewed. Radiological features of contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) in patients with cHCC-CCA were reevaluated by a radiologist. Factors association with disease-free survival (DFS) and overall survival (OS) were analyzed. RESULTS: The mean age of cHCC-CCA, HCC and ICC was similar. Hepatitis B virus infection was prevalent in patients with cHCC-CCA (22/30, 73.3%). Most (70%) of the cHCC-CCA had atypical radiological pattern of HCC and belonged to classic type in pathological features. cHCC-CCA and ICC had worse DFS, but the 5-year OS of cHCC-CCA was substantial adequate after surgery. Of the 891 patients, male gender, advanced T stage, multiple tumor number, alpha-fetoprotein (AFP) level >20 ng/ml, cHCC-CCA, and ICC were factors associated with poor DFS in multivariable analysis. Older age, T stage 3 or 4, presence of macrovascular invasion, AFP >20 ng/mL, cHCC-CCA, and ICC were factors significantly associated with OS. CONCLUSION: cHCC-CCA is associated with high risk of recurrence following surgical resection as compared with HCC. Closely post-operative monitoring is highly recommended.

A New Prognostic Model Based on Albumin-Bilirubin Grade for Hepatocellular Carcinoma Beyond the Milan Criteria.

BACKGROUND: The survival of patients with advanced hepatocellular carcinoma (HCC) is highly variable due to heterogeneous tumoral characteristics. We proposed and validated an albumin-bilirubin (ALBI)-based model for HCC beyond Milan criteria, the ALBI-HOME, for these patients. METHODS: A total of 2186 patients were enrolled and randomly assigned to the derivation cohort (n = 1093) and validation cohort (n = 1093). Multivariate Cox proportional hazards model was used to determine significant prognostic factors in the derivation cohort. The performance of ALBI-HOME was evaluated in the validation cohort. RESULTS: In the Cox model, six factors were identified as independent predictors of poor survival: ALBI grade 2 [hazard ratio (HR) 1.848, 95% confidence incidence (CI) 1.556-2.195, p < 0.001], ALBI grade 3 (HR 3.266, 95% CI 2.531-4.215, p < 0.001), serum AFP ≥ 100 ng/ml (HR 1.482, 95% CI 1.279-1.717, p < 0.001), total tumor volume ≥ 250 cm3 (HR 1.503, 95% CI 1.294-1.746, p < 0.001), ascites (HR 1.400, 95% CI 1.187-1.561, p < 0.001), performance status 0-1 (HR 1.756, 95% CI 1.485-2.076 p < 0.001), and vascular invasion or metastasis (HR 2.110, 95% CI 1.809-2.0, p < 0.001). The ALBI-HOME is based on these six parameters, and the score ranges from 0 to 7. This model was associated with the best prognostic ability among different HCC staging systems to predict survival in patients beyond Milan criteria; its ability remained consistently stable in different treatment subgroups and viral etiologies. CONCLUSIONS: The proposed ALBI-HOME is a simple and feasible predictive model for HCC beyond Milan criteria. It demonstrates superior prognostic performance among the currently used staging systems and may help identify at-risk patients to undergo more aggressive treatments.

An Albumin-Bilirubin (ALBI) Grade-based Prognostic Model For Patients With Hepatocellular Carcinoma Within Milan Criteria.

OBJECTIVE: The Milan criteria are recommended as the major reference for liver transplantation in patients with small hepatocellular carcinoma (HCC). However, alternative anticancer treatments are often utilized due to severe donor organ shortage. This study aimed to develop and validate an albumin-bilirubin (ALBI) grade-based prognostic model to stratify survival in patients within Milan criteria undergoing nontransplant therapy. PATIENTS AND METHODS: A total of 1655 patients were assigned into the derivation and validation cohort according to treatment modalities. Multivariate analysis was used to identify independent predictors of survival in the derivation cohort. An ALBI-based model was evaluated in the validation cohort. RESULTS: In the Cox multivariate model, age 65 years or older (hazard ratio [HR]=1.576, P<0.001), serum α-fetoprotein (AFP) level >100 ng/mL (HR=1.671, P<0.001), ascites (HR=1.808, P<0.001), performance status 1 to 4 (HR=1.738, P<0.001), ALBI grade 2 (HR=1.827, P<0.001), and ALBI grade 3 (HR=3.589, P<0.001) were independent predictors of poor survival in the derivation cohort. An ALBI-based prognostic model with a total of 0 to 6 points was derived with the sum of 5 variables: 1 point each for age 65 years or older, AFP >100 ng/mL, presence of ascites, performance status 1 to 4, and ALBI grade 2, and 2 points for ALBI grade 3. This model can accurately predict long-term outcome in the validation cohort (P<0.001) and discriminate survival in patients stratified by curative and noncurative treatments (both P<0.001). CONCLUSION: The proposed ALBI grade-based model is feasible in predicting survival in HCC patients within the Milan criteria, and helps identify high-risk patients who need timely liver transplantation.

Esophageal varices are not predictive of patient prognosis after surgical resection of hepatocellular carcinoma.

OBJECTIVE: The predictive value of esophageal varices (EV) in determining the patient outcome in hepatocellular carcinoma (HCC) remains unresolved. We aimed to assess the impact of EV on the prognosis of HCC patients after surgical resection. MATERIALS AND METHODS: We consecutively enrolled 446 treatment-naive HCC patients who underwent surgical resection and esophagogastroduodenoscopy from 2003 to 2015. Prognostic factors were analyzed using the Cox proportional hazards model and a propensity score matching analysis. RESULTS: A total of 89 (20.0%) HCC patients presented with EV. Compared with those without EV, patients with EV had poorer preservation of liver function and higher rates of cirrhosis in the nontumor part of liver specimens. After a median follow-up period of 34.6 months (25-75 percentiles; 12.8-59.3 months), 130 patients had died. The cumulative 5-year overall survival (OS) rates were 62.3 and 70.6% in patients with and without EV, respectively (P=0.102). A multivariate analysis showed that serum albumin level less than or equal to 4 g/dl (P=0.020), α-fetoprotein level greater than 20 ng/ml (P<0.001), as well as the presence of vascular invasion (P<0.001), but not the presence of EV, were independent risk factors associated with poor OS. Moreover, 67 patients were matched in each group using the one-to-one nearest-neighbor matching method. After matching, the OS rates were comparable between HCC patients with and without EV. CONCLUSION: EV is not an independent risk factor predictive of poor prognosis for HCC patients after resection surgery if they have well-preserved liver function.

C-Reactive Protein (CRP) is a Promising Diagnostic Immunohistochemical Marker for Intrahepatic Cholangiocarcinoma and is Associated With Better Prognosis.

Differential diagnosis of intrahepatic cholangiocarcinoma (iCCA) from its histologic mimickers, especially metastatic adenocarcinomas of gastric and pancreatic origin, is a great challenge for pathologists. In this study, through bioinformatics analysis of data from The Cancer Genome Atlas and Gene Expression Omnibus, we identified C-reactive protein (CRP) as a candidate marker to differentiate iCCA from other adenocarcinomas and validated its diagnostic performance by immunohistochemistry in a large cohort of clinical samples including 103 iCCAs, 384 other adenocarcinomas, and 34 liver metastases of various origins. The sensitivity and specificity of CRP expression in the diagnosis of iCCA were 75.7% and 91.1% when using tissue microarrays and 93.3% and 88.2% when using whole tissue sections, respectively. We also compared the diagnostic performance of CRP with N-cadherin, a previously reported marker for iCCA. The sensitivity and specificity of N-cadherin were 54.4% and 92.2% when using tissue microarrays and 80.0% and 88.2% when using whole tissue sections, respectively. The sensitivity of CRP was higher than that of N-cadherin, whereas their specificity was similar. CRP expression was associated with mass-forming gross type (P<0.001), absence of perineural invasion (P=0.002), and N-cadherin expression (P<0.001). CRP expression was also associated with better overall survival (P=0.002) and longer recurrence-free time (P=0.032) after surgery. Our study suggests that CRP is a promising immunohistochemical marker to differentiate iCCA from other adenocarcinomas. Compared with N-cadherin, CRP showed higher sensitivity and similar specificity. CRP expression was associated with better prognosis in iCCA.

Evaluation of prognostic factors and implication of lymph node dissection in intrahepatic cholangiocarcinoma: 10-year experience at a tertiary referral center.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver malignancy, and surgical resection remains the only potentially curative treatment. However, the existing literature indicates that those prognostic factors associated with outcome after surgery remain poorly defined. METHODS: Data were retrospectively collected from 103 patients with ICC who underwent surgical resection between 2005 and 2014. The patients were divided into two groups: one with (D1) and one without (D0) lymph node dissection of hepatic hilum according to the surgery performed. Thereafter, the prognostic values of clinicopathological characteristics were evaluated. RESULTS: The median overall survival (OS) after surgical resection of ICC was 43.9 months [95% confidence interval (CI), 11.6-76.2 months]. The 1-, 3-, and 5-year OS rates were 85.5%, 52.8%, and 45.6%, respectively. Multivariable analysis showed that lymph node metastases [hazard ratio (HR), 6.70; 95% CI, 2.18-20.55], positive resection margins (HR, 2.67; 95% CI, 1.14-6.23), periductal infiltration (HR, 3.64; 95% CI, 1.27-10.44), and poor differentiation (HR, 2.90; 95% CI, 1.41-5.95) were independently associated with poor survival. There were no significant differences in clinicopathological characteristics between D1 and D0 groups, except for vascular invasion (p = 0.018) and perineural invasion (p = 0.008). In the D1 group, lymph node metastases were associated with late T stages, multiple tumors, and elevated serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels. CONCLUSION: Regional lymph node metastasis, positive resection margin, periductal infiltration, and poor differentiation were poor prognostic factors in patients with ICC after curative surgery. Lymph node dissection did not show survival benefits, but was useful for nodal staging. However, lymph node metastases were strongly associated with late T stages, multiple tumors, and elevated serum CEA and CA19-9 levels.