Towards an actionable One Health approach.

BACKGROUND: Despite the increasing focus on strengthening One Health capacity building on global level, challenges remain in devising and implementing real-world interventions particularly in the Asia-Pacific region. Recognizing these gaps, the One Health Action Commission (OHAC) was established as an academic community for One Health action with an emphasis on research agenda setting to identify actions for highest impact. MAIN TEXT: This viewpoint describes the agenda of, and motivation for, the recently formed OHAC. Recognizing the urgent need for evidence to support the formulation of necessary action plans, OHAC advocates the adoption of both bottom-up and top-down approaches to identify the current gaps in combating zoonoses, antimicrobial resistance, addressing food safety, and to enhance capacity building for context-sensitive One Health implementation. CONCLUSIONS: By promoting broader engagement and connection of multidisciplinary stakeholders, OHAC envisions a collaborative global platform for the generation of innovative One Health knowledge, distilled practical experience and actionable policy advice, guided by strong ethical principles of One Health.

Hepatectomy combined with apatinib and camrelizumab for CNLC stage IIIb hepatocellular carcinoma: a phase II trial protocol.

INTRODUCTION: Current clinical guidelines recommend systematic antitumour therapy as the primary treatment option for patients with stage IIIb hepatocellular carcinoma (HCC) based on the China liver cancer (CNLC) staging criteria. Several different targeted therapeutics have been applied in combination with immunotherapeutic regimens to date in patients with advanced HCC. The present study was developed to evaluate the relative safety and efficacy of hepatectomy of HCC in combination with targeted apatinib treatment and immunotherapeutic camrelizumab treatment CNLC-IIIb stage HCC patients with the goal of providing evidence regarding the potential value of this therapeutic regimen in individuals diagnosed with advanced HCC. METHODS AND ANALYSIS: This is a multicentre phase II trial with single-arm in which patients undergo hepatectomy in combination with targeted treatment (apatinib) and immunotherapy (camrelizumab). Patients will undergo follow-up every 2-3 months following treatment initiation to record any evidence of disease progression and adverse event incidence for a minimum of 24 months following the discontinuation of treatment until reaching study endpoint events or trial termination. The primary endpoint for this study is patient mortality. ETHICS AND DISSEMINATION: This study protocol was approved by the Ethics Committee of the Guangxi Medical University Cancer Hospital (KS2022[124]). The results of this study will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT05062837.

Prognostic significance of combined α-fetoprotein and CA19-9 for hepatocellular carcinoma after hepatectomy.

BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) varies considerably among patients with the same disease stage and characteristics, and only about two thirds show high levels of α-fetoprotein (AFP), a common prognostic indicator for HCC. Here, we assessed whether the combination of presurgical serum levels of AFP and carbohydrate antigen 19-9 (CA19-9) can predict the prognosis of HCC patients after hepatectomy. METHODS: The clinicopathological characteristics and post-hepatectomy outcomes of 711 HCC patients were retrospectively reviewed. The patients were classified into three groups based on whether their preoperative serum levels of both AFP and CA19-9 were higher than the respective cut-offs of 400 ng/ml and 37 U/ml [double positive (DP)], the level of only one marker was higher than the cut-off [single positive (SP)], or neither level was higher than the cut-off [negative (N)]. The overall survival (OS) and recurrence-free survival (RFS) rates were estimated using Kaplan-Meier curves. Univariate and multivariate survival analyses were performed to identify the clinicopathological factors significantly associated with HCC prognosis. RESULTS: The 1-year, 3-year, and 5-year RFS and OS rates in the N group were significantly higher than those in the SP group, while the DP group showed the lowest rates. Multivariate Cox regression analysis showed that large tumor size (> 5 cm), multiple tumors (≥ 2), incomplete tumor capsule, positive microvascular invasion, Barcelona Clinic Liver Cancer C stage, and CA19-9 level > 37 U/mL were independent risk factors for RFS and OS in HCC patients. Moreover, aspartate aminotransferase levels > 40 U/L proved to be an independent prognostic factor for OS. CONCLUSION: The combination of serum AFP and CA19-9 levels may be a useful prognostic marker for HCC patients after hepatectomy.

Combining stereotactic body radiotherapy with camrelizumab for unresectable hepatocellular carcinoma: a single-arm trial.

PURPOSE: Stereotactic body radiotherapy (SBRT) may have significant immunomodulatory effects that enhance tumor response to immune checkpoint inhibitors. This phase 2 clinical trial was conducted to evaluate the safety and efficacy of combining palliative SBRT with camrelizumab (an anti-PD1 monoclonal antibody) in patients with unresectable hepatocellular carcinoma (uHCC). METHODS: Patients with uHCC, Child-Pugh A/B liver function, and at least one measurable lesion were enrolled between April 2020 and August 2022. Patients were administered 200 mg camrelizumab intravenously from the first day of palliative SBRT and then every 3 weeks. Palliative SBRT was delivered daily over five fractions per week, with a dose range of 30-50 Gy. The primary endpoints were objective response rate (ORR) and safety. This trial was registered at ClinicalTrials.gov (NCT04193696). RESULTS: Twenty-one patients were enrolled; the median radiation dose was 40 Gy, and the median number of cycles of camrelizumab was five. The ORR was 52.4%. After a median follow-up of 19.7 months, the median progression-free and overall survival were 5.8 and 14.2 months, respectively. The overall survival probability was 85.7% at 6 months, 76.2% at 9 months, and 59.9% at 12 months. All grade 3 treatment-related adverse events (TRAEs) occurred in five patients (23.8%) and were manageable. No grade 4/5 TRAEs were observed. CONCLUSION: Palliative SBRT plus camrelizumab showed promising antitumor activity against uHCC. Toxicities were manageable with no unexpected safety issues. This study provides evidence of a new therapeutic method for the treatment of uHCC.

Clinical implications and biological features of a novel postoperative recurrent HCC classification: A multi-centre study.

BACKGROUND & AIMS: The multiplicity of hepatocellular carcinoma (HCC) recurrence patterns is the most important determinant of patients' postsurgical survival. A systematic HCC recurrence classification is needed to help prevent and treat postoperative HCC recurrence in the era of precision medicine. METHODS: A total of 1319 patients with recurrent HCC from four hospitals were enrolled and divided into a development cohort (n = 916), internal validation cohort (n = 225) and external validation cohort (n = 178). A comprehensive study of patients' clinicopathological factors and biological features was conducted. RESULTS: Four subtypes of recurrence were identified, which integrated recurrence features, survival, effects on systemic and liver function and potential therapeutics after recurrence: type I (solitary-intrahepatic oligorecurrence); type II (multi-intrahepatic oligorecurrence); type III (progression recurrence) and type IV (hyper-progression recurrence). Type III~IV recurrence indicated exceptionally poor prognosis. Subsequently, two nomogram models were established for type III~IV recurrence prediction, and both demonstrated excellent predictive performance and applicability of pre and postoperative strategy formulation. Multiple biological analyses revealed that HCC cases with type III~IV recurrence were characterized by enrichment in p53 mutations, CCND1 amplification, high proliferation/metastasis potential, inactive metabolism and immune exhaustion features. Over-expression of high mobility group protein 2 (HMGA2) enhanced the highly malignant behaviour of HCC through multiple molecular pathways, making it a potential prognostic predictor and therapeutic target. CONCLUSIONS: This 'recurrent HCC classification' has important potential value in identifying patients with surgical benefit, predicting postsurgical survival and guiding treatment strategies. Multidimensional biological insights also increased knowledge of factors associated with HCC recurrence.

Lenvatinib with or without immune checkpoint inhibitors for patients with unresectable hepatocellular carcinoma in real-world clinical practice.

BACKGROUND: Lenvatinib is regarded as the first-line therapy for patients with unresectable hepatocellular carcinoma (HCC). This study assessed the efficacy and safety of lenvatinib with or without immune checkpoint inhibitors (ICIs) in patients with unresectable HCC. METHODS: In this multicentric retrospective study, patients with unresectable HCC who treated with lenvatinib with or without ICIs would be enrolled. Overall survival, progression-free survival, objective response rate, and disease control rate were calculated to assess the antitumor response. RESULTS: Between January 2019 and August 2020, 65 patients received lenvatinib plus ICIs while other 45 patients received lenvatinib. The baseline characteristics were comparable between the two groups. Lenvatinib plus ICIs provided significantly higher overall survival (hazard ratio = 0.47, 95% CI 0.26-0.85; p = 0.013) and progression-free survival (hazard ratio = 0.35, 95% CI 0.20-0.63; p < 0.001) than lenvatinib monotherapy. Moreover, patients with lenvatinib plus ICIs had significantly higher objective response rate (41.5% vs 20.0%, p = 0.023) and disease control rate (72.3% vs 46.7%, p = 0.009) per RECIST v1.1 than those with lenvatinib. No treatment-related deaths were observed. Grade 3 or greater adverse events occurring in 10% or more of patients in either treatment group were hypertension [13 (20.0%) of 65 patients treated with lenvatinib plus ICIs vs 8 (17.8%) of 45 patients treated with lenvatinib], and palmar-plantar erythrodysesthesia [seven (10.8%) vs two (4.4%)]. CONCLUSIONS: In this real-world study, lenvatinib combined with ICIs showed significantly promising efficacy and manageable safety than lenvatinib alone in patients with unresectable HCC.

S100P as a novel biomarker of microvascular invasion and portal vein tumor thrombus in hepatocellular carcinoma.

BACKGROUND: Portal vein tumor thrombus (PVTT) and microvascular invasion (MVI) are types of intrahepatic vascular metastasis of hepatocellular carcinoma (HCC) and are highly correlated with poor prognosis. However, the underlying biomarkers of PVTT and MVI are unclear. METHODS: We identified a PVTT/MVI-associated gene S100P by cDNA microarray analysis, and assess the potential value of serum S100P measurement in the differential diagnosis of HCC and prediction of MVI status with large retrospective and perspective cohort studies. RESULTS: The mRNA and protein of S100P was increased in HCCs with PVTT or MVI. High S100P immunostaining in tumors was correlated with inferior tumor-free survival. Serum S100P values discriminated patients with HCCs from those with benign liver tumors, and it showed predictive potential of MVI status in both retrospective and perspective cohorts. S100P may regulate HCC tumorigenicity and invasive ability; S100P also was associated with up-regulation of CD44, which may mediate HCC cell adhesion to form PVTT/MVI. CONCLUSIONS: Serum S100P may be a novel differential diagnostic marker for HCC and a potential predictor of MVI status pre-surgery for HCC patients. S100P overexpression in HCC is highly correlated with the formation of PVTT and MVI, which may make S100P as a potential therapeutic target for HCC metastasis.

Perioperative antiviral therapy improves the prognosis of HBV DNA-negative patients with HBV-related hepatocellular carcinoma.

OBJECTIVE: To investigate the effect of perioperative antiviral therapy on the prognosis of hepatitis B virus (HBV) DNA-negative patients with HBV-related hepatocellular carcinoma (HCC). METHODS: The clinical data of 140 patients who were positive for hepatitis B surface antigen (HBsAg) but negative for HBV DNA before partial hepatectomy were retrospectively analyzed. Propensity score matching (PSM) was used to eliminate the influence of confounding factors on prognosis. Postoperative liver function, HBV reactivation rate, recurrence-free survival (RFS) and overall survival (OS) were compared between antiviral and non-antiviral therapy groups. RESULTS: Compared with the non-antiviral therapy group, the antiviral therapy group had a lower rate of HBV reactivation and better postoperative liver function (P < 0.05). The 1-year, 2-year and 3-year survival rates of the antiviral therapy group were better than those of the non-antiviral therapy group before or after PSM (P < 0.05). Prognostic analysis excluding 11 patients with HBV reactivation showed that perioperative antiviral therapy could significantly improve OS (P = 0.004), but had no significant effect on RFS (P = 0.056). Multivariate analyzes showed that antiviral therapy was associated with better OS. CONCLUSION: Perioperative antiviral therapy can significantly reduce the risk of HBV reactivation and improve postoperative liver function, RFS and OS.

Dose-Response Between Serum Prealbumin and All-Cause Mortality After Hepatectomy in Patients With Hepatocellular Carcinoma.

BACKGROUND: The relationship between serum prealbumin and the risk of all-cause mortality after hepatectomy in patients with hepatocellular carcinoma (HCC) needs to be evaluated. METHODS: We conducted a retrospective study. A Cox proportional hazards regression model was used to adjust for potential confounders. Prealbumin level was transformed by Z-scores and categorized into quartiles (Q1: <147 mg/L, Q2: 147-194 mg/L, Q3: 194-239 mg/L, Q4: >239 mg/L). We assessed the dose-response relationship between serum prealbumin and the risk of all-cause mortality using a restricted cubic spline model. RESULTS: Data were included from 2,022 HCC patients who underwent hepatectomy at Guangxi Medical University Cancer Hospital in China between January 2006 and January 2016. The adjusted hazard ratios (HRs) for increasing quartiles of serum prealbumin were 0.78 [95% confidence interval (CI): 0.64-0.95] for Q2, 0.66 (0.53-0.81) for Q3, and 0.51 (0.41-0.64) for Q4 in the Cox model (all P < 0.001). Serum prealbumin showed an L-shaped, non-linear dose-response relationship with the risk of all-cause mortality (P < 0.001). Among patients whose serum prealbumin was below 250 mg/L, risk of all-cause mortality decreased by 27% (95% CI: 18-36%) per increase of one standard deviation (69.8 mg/L) in serum prealbumin. CONCLUSIONS: Levels of serum prealbumin under 250 mg/L may be considered dangerous with respect to all-cause mortality after hepatectomy in HCC patients. Serum prealbumin may be useful as a prognostic marker in HCC patients undergoing hepatectomy.

Outcomes of anatomical versus non-anatomical resection for hepatocellular carcinoma according to circulating tumour-cell status.

Background and aims: Hepatic resection is the first-line treatment for hepatocellular carcinoma (HCC). Whether to perform anatomical (AR) or non-anatomical resection (NAR) remains controversial. This retrospective study compares the outcomes according to the number and type of circulating tumour cells (CTCs).Methods: The cohort included 136 patients with HCC treated with R0 resection between 2014 and 2017. CanPatrol CTC-enrichment technique was used to enrich and classify CTCs according to epithelial-to-mesenchymal transition phenotype.Results: 91.91% of total patients were CTC-positive, with 91.23% in the AR group and 92.41% in the NAR group. Tumour-free survival (TFS) did not differ significantly between the two groups. However, TFS was significantly higher in patients with low CTCs count and mesenchymal- and epithelial/mesenchymal-negative phenotypes. As for the incidence and types of recurrence, high pre-resection CTC count and mesenchymal- and epithelial/mesenchymal-positivity were significantly associated with extrahepatic and multi-intrahepatic recurrence. Higher morbidities for hepatic failure and ascites were observed in patients treated by AR.Conclusion: AR may be more beneficial than NAR only in patients with low CTC count and mesenchymal- and epithelial/mesenchymal-negative phenotypes. For patients with a high CTC count, the balance between operative risk and prognostic benefit is more important than the resection method performed.Key messagesAnatomic resection may improve the survival of HCC patients, but only those with low CTC count and negative M- and E/M-CTC phenotypes.CTC analysis before surgery can be used to better guide the choice of resection method for HCC.

Evaluation of liver regeneration and post-hepatectomy liver failure after hemihepatectomy in patients with hepatocellular carcinoma.

Aim: To explore clinical factors associated with extent of liver regeneration after hemihepatectomy to treat hepatocellular carcinoma (HCC).Methods: Future liver remnant volume (as a percentage of functional liver volume, %FLRV) and remnant liver volume were measured preoperatively and at 1, 5, 9, and 13 weeks postoperatively.Results: After hepatectomy, 1 of 125 patients (0.8%) died within 3 months, 13 (10.4%) experienced liver failure, and 99 (79.2%) experienced complications. %FLRV was able to predict liver failure with an area under the receiver operating characteristic curve of 0.900, and a cut-off value of 42.7% showed sensitivity of 85.7% and specificity of 88.6%. Postoperative median growth ratio was 21.3% at 1 week, 30.9% at 5 weeks, 34.6% at 9 weeks, and 37.1% at 13 weeks. Multivariate analysis identified three predictors associated with liver regeneration: FLRV < 601 cm3, %FLRV, and liver cirrhosis. At postoperative weeks (POWs) 1 and 5, liver function indicators were significantly better among patients showing high extent of regeneration than among those showing low extent, but these differences disappeared by POW 9.Conclusions: FLRV, %FLRV, and liver cirrhosis strongly influence extent of liver regeneration after hepatectomy. %FLRV values below 42.7% are associated with greater risk of post-hepatectomy liver failure.

The screening and identification of the biological control fungi Chaetomium spp. against wheat common root rot.

Bipolaris sorokiniana is a soil-borne fungal pathogen causing common root rot in wheat, and is difficult to control through chemical and agricultural means. Chaetomium spp. have been documented as potential biological control agents for plant diseases. In this study, seven Chaetomium strains were screened for their abilities to control B. sorokiniana on agar plates. Strain 22-10 significantly inhibited the growth of B. sorokiniana on potato dextrose agar plates, up to 66.7%. Its filtrate of liquid culture also inhibited the mycelial growth of B. sorokiniana, indicating that strain 22-10 produced secondary metabolites against B. sorokiniana. The incidence and disease indexes of common root rot significantly decreased in wheat after treatment with the crude extract of strain 22-10. Six active compounds were purified from crude extract of this fungus culture against B. sorokiniana. Chaetoviridin A showed the highest efficiency to inhibit the growth of B. sorokiniana. Strain 22-10 was identified as Chaetomium globosum based on phylogenetic analysis of the rDNA internal transcribed spacer region and microscopic characteristics. The high control efficiency of strain 22-10 of C. globosum against B. sorokiniana suggested it has potential to be a biocontrol agent for B. sorokiniana.

Circulating Tumor Cells Undergoing EMT Provide a Metric for Diagnosis and Prognosis of Patients with Hepatocellular Carcinoma.

To clarify the significance of circulating tumor cells (CTC) undergoing epithelial-mesenchymal transition (EMT) in patients with hepatocellular carcinoma (HCC), we used an advanced CanPatrol CTC-enrichment technique and in situ hybridization to enrich and classify CTC from blood samples. One hundred and one of 112 (90.18%) patients with HCC were CTC positive, even with early-stage disease. CTCs were also detected in 2 of 12 patients with hepatitis B virus (HBV), both of whom had small HCC tumors detected within 5 months. CTC count ≥16 and mesenchymal-CTC (M-CTC) percentage ≥2% prior to resection were significantly associated with early recurrence, multi-intrahepatic recurrence, and lung metastasis. Postoperative CTC monitoring in 10 patients found that most had an increased CTC count and M-CTC percentage before clinically detectable recurrence nodules appeared. Analysis of HCC with high CTC count and high M-CTC percentage identified 67 differentially expressed cancer-related genes involved in cancer-related biological pathways (e.g., cell adhesion and migration, tumor angiogenesis, and apoptosis). One of the identified genes, BCAT1, was significantly upregulated, and knockdown in Hepg2, Hep3B, and Huh7 cells reduced cell proliferation, migration, and invasion while promoting apoptosis. A concomitant increase in epithelial marker expression (EpCAM and E-cadherin) and reduced mesenchymal marker expression (vimentin and Twist) suggest that BCAT1 may trigger the EMT process. Overall, CTCs were highly correlated with HCC characteristics, representing a novel marker for early diagnosis and a prognostic factor for early recurrence. BCAT1 overexpression may induce CTC release by triggering EMT and may be an important biomarker of HCC metastasis.Significance: In liver cancer, CTC examination may represent an important "liquid biopsy" tool to detect both early disease and recurrent or metastatic disease, providing cues for early intervention or adjuvant therapy. Cancer Res; 78(16); 4731-44. ©2018 AACR.

Optimizing stage of single large hepatocellular carcinoma: A study with subgroup analysis by tumor diameter.

This study aims to refine the designation for single hepatocellular carcinoma (HCC) >5 cm by comparing the postresection prognosis of these patients with those who have a single-tumor ≤5 cm and those with stage B.Patients with a single-tumor were classified into subgroups based on diameter. Of the 1132 patients analyzed, 426 had a single-tumor >2 and ≤5 cm; 229, a single-tumor >5 and ≤8 cm; 52, a single-tumor >8 and < 10 cm; 150, a single-tumor ≥10 cm; and 275, stage B.Hospital mortality and complications increased with tumor size among the single-tumor subgroups and median survival decreased with increasing of tumor size. Overall survival (OS) among patients with a single-tumor >5 cm was significantly lower than among patients with a single-tumor >2 and ≤5 cm (P ≤ .001), but significantly higher than among patients with clearly stage B (P ≤ .001). Patients with a single-tumor >5 and ≤8 cm showed lower OS than patients with a single-tumor >2 and ≤5 cm (P < .001). Patients with a single-tumor >8 and <10 cm or a single-tumor ≥10 cm showed lower OS than patients with a single-tumor >5 and ≤8 cm (P = .033 and .006), and similar OS to patients with stage B (P = .323).Patients with a single-tumor >5 and ≤8 cm may be assigned to a new stage between early and intermediate. Patients with a single-tumor >8 cm may be assigned to intermediate stage.

Tumor stage and primary treatment of hepatocellular carcinoma at a large tertiary hospital in China: A real-world study.

The current clinical reality of tumor stages and primary treatments of hepatocellular carcinoma (HCC) is poorly understood. This study reviewed the distribution of tumor stages and primary treatment modalities among a large population of patients with primary HCC. Medical records of patients treated between January 2003 and October 2013 for primary HCC at our tertiary hospital in China were retrospectively reviewed. A total of 6241 patients were analyzed. The distribution of Barcelona Clinic Liver Cancer (BCLC) stages was as follows: stage 0/A, 28.9%; stage B, 16.2%; stage C, 53.6%; stage D, 1.3%. The distribution of Hong Kong Liver Cancer (HKLC) stages was as follows: stage I, 8.4%; stage IIa, 1.5%; stage IIb, 29.0%; stage IIIa, 10.0%; stage IIIb, 33.6%; stage IVa, 3.4%; stage IVb, 2.5%; stage Va, 0.2%; stage Vb, 11.4%. The most frequent therapy was hepatic resection for patients with BCLC-0/A/B disease, and transarterial chemoembolization for patients with BCLC-C disease. Both these treatments were the most frequent for patients with HKLC I to IIIb disease, while systemic chemotherapy was the most frequent first-line therapy for patients with HKLC IVa or IVb disease. The most frequent treatment for patients with HKLC Va/Vb disease was traditional Chinese medicine. In conclusion, Prevalences of BCLC-B and -C disease, and of HKLC I to IIIb disease, were relatively high in our patient population. Hepatic resection and transarterial chemoembolization were frequent first-line therapies.

Effects of antiviral therapy on post-hepatectomy HBV reactivation and liver function in HBV DNA-negative patients with HBV-related hepatocellular carcinoma.

The ability of antiviral therapy to reduce risk of post-hepatectomy hepatitis B virus (HBV) reactivation in patients negative for viral DNA is unclear. This prospective study involved 174 consecutive patients with hepatitis B virus related hepatocellular carcinoma who were negative for hepatitis B virus DNA in serum and who underwent hepatic resection. Hepatitis B virus reactivation occurred in 30 patients in the non-antiviral group (27.8%) but in only 2 patients in the antiviral group (3.0%, P < 0.001). Based on multivariate analysis, risk of hepatitis B virus reactivation was associated with minor hepatectomy and absence of antiviral therapy. Liver function indicators at one week after resection did not differ significantly between the two groups, or between patients who experienced hepatitis B virus reactivation or not. Nevertheless, alanine aminotransferase and albumin at 1 month after resection were significantly higher in the antiviral group than in the non-antiviral group, and they were significantly higher in patients who did not experience hepatitis B virus reactivation than in those who did. Therefore, patients with hepatitis B virus related hepatocellular carcinoma face substantial risk of hepatitis B virus reactivation after hepatectomy, even if they are negative for viral DNA at baseline. Antiviral therapy can reduce the risk of reactivation, helping improve liver function after surgery.

Adefovir dipivoxil is less expensive than lamivudine and associated with similar prognosis in patients with hepatitis B virus-related hepatocellular carcinoma after radical resection.

AIM: Lamivudine (LAM) and adefovir dipivoxil (ADV) are widely used in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), but few studies have directly compared their therapeutic efficacy and treatment cost. This study aims to compare LAM with ADV head-to-head in these patients. METHODS: We retrospectively analyzed 201 patients with HBV-related HCC who underwent radical resection and subsequently received LAM (n=155) or ADV (n=46). The two groups were compared in terms of HBV-DNA levels, liver function, antiviral resistance, recurrence-free, and overall survival, as well as antiviral medication costs. RESULTS: Despite significant improvement in HBV-DNA and alanine aminotransferase level in the LAM group after 1 year of antiviral therapy, these parameters did not differ significantly between the two groups over the following 2 years. Incidence of antiviral resistance after 1, 2, and 3 years of antiviral treatment was significantly higher in the LAM group (19.5%, 45.7%, and 56.4%) than in the ADV group (0%, 3.3%, and 14.5%; P<0.001). Overall survival at 1, 2, and 3 years after resection was similar for the LAM group (84.5%, 69.3%, and 64.6%) and the ADV group (84.1%, 77.8%, and 63.4%; P=0.905). Recurrence-free survival at the three follow-up points was also similar for the LAM group (71.7%, 58.3%, and 43.9%) and the ADV group (81.1%, 66.1%, and 53.0%; P=0.452). Cox regression analysis confirmed that both nucleos(t)ide analogues were associated with similar overall and recurrence-free survival. However, the average medication costs after 1, 2, and 3 years of antiviral treatment were significantly higher in the LAM group (€3.0, €4.8, and €5.6 per person per day) than in the ADV group (€2.2, €2.4, and €3.1 per person per day; all P<0.05). CONCLUSION: ADV and LAM are associated with similar survival benefit in patients with HBV-related HCC after radical resection, but ADV is more cost-effective.

Association between age and overall survival of patients with hepatocellular carcinoma after hepatic resection.

AIM: The suitability of hepatic resection for older patients remains controversial. This study aimed to investigate whether age influences overall survival of patients with hepatocellular carcinoma (HCC) after resection. METHODS: Records of 1,132 patients with HCC after hepatic resection were retrospectively reviewed. Overall survival (OS) was compared between younger and older patients based on five cut-off ages (30, 40, 50, 60, and 70 years). RESULTS: Across all patients, OS was 89.7% at 1 year, 67.7% at 3 years, and 47.7% at 5 years. OS was similar between younger and older patients at all cut-off ages (all P > 0.1), but OS was marginally lower among patients >70 years old than those ≤70 (P = 0.090). Multivariate analyses identified several risk factors for lower OS: preoperative serum albumin <35 g/L, alanine aminotransferase >80 U/L, α-fetoprotein ≥400 ng/ml, presence of esophagogastric varices or macrovascular invasion, incomplete/absent tumor capsule, tumor size >10 cm, tumor number ≥3, and major hepatectomy. CONCLUSION: Age does not influence the prognosis of patients with HCC after hepatic resection. Older patients should be considered for curative resection if remnant liver volume and liver function are adequate. J. Surg. Oncol. 2016;114:966-970. © 2016 Wiley Periodicals, Inc.

Feasibility of combining adjuvant transarterial chemoembolization with nucleos(t)ide analog therapy for patients with HBV-associated hepatocellular carcinoma after hepatectomy.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-associated mortalities, and its prevalence is expected to increase in future decades. Hepatitis B virus (HBV) infection is the leading cause of HCC. Although hepatectomy is the preferred curative treatment for HCC, tumor recurrence is common, which is the most frequent cause of mortality in patients with HCC. HCC recurrence may originate from the primary tumor or be associated with remnant liver tissue, and include high viral load and hepatic inflammatory activity. Adjuvant transarterial chemoembolization and postoperative nucleos(t)ide analogs therapy are the two corresponding therapies. Following systematic searching of the PubMed database, the indications for adjuvant transarterial chemoembolization and nucleos(t)ide analog therapies for HBV-related HCC after hepatectomy were acquired. Additionally, the feasibility of combining these two therapies were also reviewed.