Postoperative adjuvant sorafenib improves survival outcomes in hepatocellular carcinoma patients with microvascular invasion after R0 liver resection: a propensity score matching analysis

BackgroundMicrovascular invasion (MVI) is a major determinant of survival outcome for hepatocellular carcinoma (HCC). This study aimed to investigate the efficacy of postoperative adjuvant Sorafenib (PA-Sorafenib) in HCC patients with MVI after R0 liver resection (LR).MethodsThe data of patients who underwent R0 LR for HCC with histologically confirmed MVI at the Eastern Hepatobiliary Surgery Hospital were retrospectively analyzed. The survival outcomes for patients who underwent PA-Sorafenib were compared with those who underwent R0 LR alone. Propensity score matching (PSM) analysis was performed.Results728 HCC patients had MVI in the resected specimens after R0 resection, with 581 who underwent LR alone and 147 patients who received in additional adjuvant sorafenib. PSM matched 113 patients in each of these two groups. The overall survival (OS) and recurrence free survival (RFS) were significantly better for patients in the PA-sorafenib group (for OS: before PSM, P = 0.003; after PSM, P = 0.007), (for RFS: before PSM, P = 0.029; after PSM, P = 0.001), respectively. Similar results were obtained in patients with BCLC 0-A, BCLC B and Child-Pugh A stages of disease.ConclusionsPA-Sorafenib was associated with significantly better survival outcomes than LR alone for HCC patients with MVI.     

Prognostic factors and predictors of postoperative adjuvant transcatheter arterial chemoembolization benefit in patients with resected hepatocellular carcinoma

BACKGROUND Postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) has improved overall survival (OS) in patients with hepatocellular carcinoma (HCC).However,the prognostic and predictive factors remain unclear.AIM To assess the prognostic factors and the predictors of PA-TACE benefit for OS in patients with resected HCC.METHODS Univariate and multivariate analyses were performed to identify the potential prognostic factors for OS.In order to assess the predictive factors of PA-TACE benefit,the interaction variables between treatments for each subgroup were evaluated using the Cox proportional hazards regression model.RESULTS A total of 378 patients (PA-TACE vs surgery alone,189:189) from three centerswere included after a propensity-score 1:1 matching analysis.Compared to the group receiving surgery alone,PA-TACE prolonged the OS rate in patients with resected HCC (P 0.001).The Barcelona Clinic Liver Cancer system and ferritinto-hemoglobin ratio (FHR) were used as the prognostic factors for OS in both groups.Age (P=0.023) and microscopic vascular invasion (MVI)(P=0.002) were also identified in the PA-TACE group,while gender (P=0.027),hepatitis B virus(P=0.034) and albumin-bilirubin grade (P=0.027) were also selected in the surgery alone group.In addition,PA-TACE resulted in longer OS than surgery alone across subgroups [all hazard ratios (PA-TACE-to-surgery alone)1].Notably,a significantly prolonged OS following PA-TACE was observed in patients with high FHR (P=0.038) and without MVI (P=0.048).CONCLUSION FHR and Barcelona Clinic Liver Cancer stages were regarded as prognostic factors for OS.Moreover,high FHR and the absence of MVI were important predictive factors,which can be used to assist clinicians in selecting which patients could achieve a better OS with PA-TACE.     

A systematic review and meta-analysis of adjuvant transarterial chemoembolization after curative resection for patients with hepatocellular carcinoma

BackgroundThe aim of this study was to systematically evaluate and determine those patients with hepatocellular carcinoma (HCC) that would benefit from the administration of postoperative adjuvant transarterial chemoembolization (PA-TACE).MethodsPubMed, Embase and Cochrane Library were searched for randomized controlled trials (RCTs) and observational studies up to July 30, 2019. The outcome of Overall survival (OS) and disease-free survival (DFS) were extracted and converted to hazard ratios (HRs) with 95% confidence intervals (95%CIs).ResultsA total of 40 studies (10 RCTs and 30 non-RCTs) involving 11,165 patients were included. Overall, PA-TACE was associated with an increased OS [HR, 0.71 (95% CI, 0.65–0.77); P < 0.001] and DFS [HR, 0.73 (95% CI, 0.66–0.80); P < 0.001]. Subgroup analysis in patients with microvascular invasion (MVI), tumor diameter >5 cm or multinodular tumors demonstrated that PA-TACE improved OS and DFS. In patients without MVI, PA-TACE showed no improvement in OS [HR, 1.14 (95% CI, 0.85–1.53); P = 0.370], and resulted in worse DFS than curative resection alone [HR, 1.20 (95% CI, 1.03–1.39); P = 0.002].ConclusionThis meta-analysis indicated that PA-TACE was beneficial in patients with HCC who were at high risk of postoperative recurrence including tumor diameter >5 cm, multinodular tumors and MVI-positive. In patients with tumor diameter ≤5 cm, single tumor or MVI-negative. PA-TACE does not appear to improve outcomes and may potentially promote postoperative recurrence in certain patients.     

Postoperative adjuvant transcatheter arterial chemoembolization should be considered selectively in patients who have hepatocellular carcinoma with microvascular invasion

Background

Microvascular invasion (MVI) is a powerful predictor of recurrence in patients who undergo liver resection for hepatocellular carcinoma (HCC). This study aimed to evaluate the efficacy of postoperative adjuvant transarterial chemoembolization (PA-TACE) in HCC patients with MVI, and further select potential patients benefitting from PA-TACE.

Postoperative adjuvant transcatheter arterial chemoembolization improves the prognosis of patients with huge hepatocellular carcinoma

Background: Surgical resection of huge hepatocellular carcinoma(HCC, ≥ 10 cm) is potentially curative. More adjuvant treatments are needed to reduce relapses in these patients. We evaluated the influence of postoperative adjuvant transcatheter arterial chemoembolization(PA-TACE) on the prognosis of huge HCC. Methods: Data from consecutive patients who underwent curative resection for huge HCC in our center were retrospectively collected. Recurrence-free survival(RFS) and overall survival(OS) were compared between patients who did and did not undergo PA-TACE. Propensity score matching(PSM) was used. Results: Among the 255 enrolled patients, 93 underwent PA-TACE. The clinical outcomes were significantly better in the PA-TACE group than those in the non PA-TACE group(5-year RFS rate: 33.5% vs. 18.0%; 5-year OS rate: 47.0% vs. 28.0%, all P 0.001). After PSM, similar results were obtained(5-year RFS rate: 28.8% vs. 17.6%, P 0.001; 5-year OS rate: 42.5% vs. 25.0%, P = 0.004). PA-TACE decreased the possibility of early recurrence( 2 years, crude cohort: P 0.001, PSM cohort: P 0.001) but not late recurrence( ≥ 2 years, crude cohort: P = 0.692, PSM cohort: P = 0.325). Multivariable Cox regression analysis suggested that PA-TACE was an independent protective factor prolonging early RFS, RFS and OS. Conclusions: PA-TACE is a safe intervention for huge HCC patients after liver resection and improves outcomes.     

The impact of resection margin and microvascular invasion on long-term prognosis after curative resection of hepatocellular carcinoma: a multi-institutional study

BackgroundThe resection margin (RM) status and microscopic vascular invasion (MVI) are known prognostic factors for hepatocellular carcinoma (HCC). An enhanced understanding of their impact on long-term prognosis is required to improve oncological outcomes.MethodsUsing multi-institutional data, the different impact of the RM status (narrow, <1 cm, or wide, ≥1 cm) and MVI (positive or negative) on overall survival (OS) and recurrence-free survival (RFS) after curative liver resection of solitary HCC without macrovascular invasion was analyzed.ResultsIn 801 patients, 306 (38%) had a narrow RM and 352 (44%) had positive MVI. The median OS and RFS were 109.8 and 74.8 months in patients with wide RM & negative MVI, 93.5 and 53.1 months with wide RM & positive MVI, 79.2 and 41.6 months with narrow RM & negative MVI, and 69.2 and 37.5 months with narrow RM & positive MVI (both P < 0.01). On multivariable analyses, narrow RM & positive MVI had the highest hazard ratio with reduced OS and RFS (HR 2.96, 95% CI 2.11–4.17, and HR 3.15, 95% CI, 2.09–4.67, respectively).ConclusionsConcomitant having narrow RM and positive MVI increases the risks of postoperative death and recurrence by about 2-fold in patients with solitary HCC.     

P53 immunohistochemical scoring：an independent prognostic marker for patients after hepatocellular carcinoma resection

AIM：To confirm if p53 mutation could be a routine predictive marker for the prognosis of hepatocellular carcinoma(HCC) patients.METHODS:Two hundreds and forth-four formalin-fixed paraffin-embedded tumor samples of the patients with HCC receiving liver resection were detected for nuclear accumulation of p53,The percent of p53 immunoreactive tumor cells was scored as 0 to 3+in p53 positive region(&lt;10%-,10-30%+,31-50%++,&gt;50%+++),Proliferating cell nuclear antigen(PCNA) and some clinicopathological characteristics,including patients‘sex,preoperative serum AFP level,tumor size,capsule,vascular invasion(both visual and microscopic),and Edmondson grade were also evaluated.RESULTS:In univariate COX harzard regression model anlaysis,tumor size Capsule status,Vascular invasion,and P53 expression were independent factor that were closely related to the overall survival(OS) rates of HCC patients.The Survival rtea of patients with 3+ for P53 expression were much lower than those with 2+or+for capsule(P&lt;0.01)were closely related to the disease-free survival(DFS) of HCC patients.IN multivariate analysis,P53 overexpression (RI 0.5456,P&lt;0.01),was the most significant factor associated with the OS rates of patients after HCC resection,While tumor size(RI 0.5209,P&lt;0.01),vascular invasion (RI0.5271,P&lt;0.01)and capsule(RI-0.8691,P&lt;0.01)were also related to the OS.However,only tumor capsular status was an independent predictive factor (P&lt;0.05),for the DFS.No significant prognostic value was found in PCNA-LI,Edmondson‘s grade,patients‘ sex and preoperative serum AFP level.CONCLUSION:Accumulation of p53 expression,as well as tumor size,capsule and vascular invasion,could be valuable markers for predicting the prognosis of HCC patients after resection.The quantitative immunohistochemical scoring for p53 nuclear accumulation might be more vaiuable for predicting prognosis of patients after HCC resection than the common qualitative analysis.     

Systematic review of the outcomes of surgical resection for intermediate and advanced Barcelona Clinic Liver Cancer stage hepatocellular carcinoma: A critical appraisal of the evidence

AIM To perform a systematic review to determine the survival outcomes after curative resection of intermediate and advanced hepatocellular carcinomas(HCC).METHODS A systematic review of the published literature was performed using the PubM ed database from 1 st January 1999 to 31 st Dec 2014 to identify studies that reported outcomes of liver resection as the primary curative treatment for Barcelona Clinic Liver Cancer(BCLC) stage B or C HCC. The primary end point was to determine the overall survival(OS) and disease free survival(DFS) of liver resection of HCC in BCLC stage B or C in patients with adequate liver reserve(i.e., Child's A or B status). The secondary end points were to assess the morbidity and mortality of liver resection in large HCC(defined as lesions larger than 10 cm in diameter) and to compare the OS and DFS after surgical resection of solitary vs multifocal HCC.RESULTS We identified 74 articles which met the inclusion criteria and were analyzed in this systematic review. Analysis of the resection outcomes of the included studies were grouped according to(1) BCLC stage B or C HCC,(2) Size of HCC and(3) multifocal tumors. The median 5-year OS of BCLC stage B was 38.7%(range 10.0-57.0); while the median 5-year OS of BCLC stage C was 20.0%(range 0.0-42.0). The collective median 5-year OS of both stages was 27.9%(0.0-57.0). In examining the morbidity and mortality following liver resection in large HCC, the pooled RR for morbidity [RR(95%CI) = 1.00(0.76-1.31)] and mortality [RR(95%CI) = 1.15(0.73-1.80)] were not significant. Within the spectrum of BCLC B and C lesions, tumors greater than 10 cm were reported to have median 5-year OS of 33.0% and multifocal lesions 54.0%.CONCLUSION Indication for surgical resection should be extended to BCLC stage B lesions in selected patients. Further studies are needed to stratify stage C lesions for resection.     

Postoperative adjuvant transarterial chemoembolization improves outcomes of hepatocellular carcinoma associated with bile duct tumor thrombus: a propensity score matching analysis

BackgroundSurgical resection is the primary treatment for hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT). This study was conducted to investigate the efficacy of postoperative adjuvant TACE (PA-TACE) in patients with HCC and BDTT.MethodsData from patients who underwent surgery for HCC with BDTT at two medical centers were retrospectively analyzed. The survival outcomes of patients who were treated by hepatic resection followed by PA-TACE were compared with those of patients who underwent surgery alone. Propensity score matching (PSM) analysis was performed with a 1:1 ratio.ResultsOf the 308 consecutively enrolled HCC patients with BDTT who underwent surgical resection, 134 underwent PA-TACE whereas 174 underwent surgery alone. From the initial cohort, PSM matched 106 pairs of patients. The OS and DFS rates were significantly better for the PA-TACE group than the surgery alone group (for OS: before PSM, P = 0.026; after PSM, P = 0.039; for DFS: before PSM, P = 0.010; after PSM, P = 0.013).ConclusionPA-TACE was associated with better survival outcomes than surgery alone for patients with HCC and BDTT. Prospective clinical trials are warranted to validate the beneficial effect of PA-TACE on HCC patients associated with BDTT.     

Preoperative Ratio of Neutrophils to Lymphocytes Predicts Postresection Survival in Selected Patients With Early or Intermediate Stage Hepatocellular Carcinoma

This study aims to clarify the prognostic value of the preoperative neutrophil-to-lymphocyte ratio (NLR) for patients with hepatocellular carcinoma (HCC) after potentially curative hepatic resection (HR). The prognostic value of the NLR for HCC patients has not been definitely reviewed by large studies, especially for those with different Barcelona Clinic Liver Cancer (BCLC) stages.A consecutive sample of 963 HCC patients who underwent potentially curative HR was classified as having low or high NLR using a cut-off value of 2.81. Overall survival (OS) and tumor recurrence were compared for patients with low or high NLR across the total population, as well as in subgroups of patients in BCLC stages 0/A, B, or C. Clinicopathological parameters, including NLR, were evaluated to identify risk factors of OS and tumor recurrence after potentially curative hepatic resection. Multivariate analyses were performed using the Cox proportional hazards model or subdistribution hazard regression model.Multivariate analyses showed that NLR (>2.81), tumor number (>3), incomplete capsule, serum albumin (≤35 g/L), alanine transaminase activity (>40 U/L), and macrovascular invasion were risk factors for low OS, whereas NLR (>2.81), tumor size (>5 cm), alpha fetal protein concentration (>400 ng/L), and macrovascular invasion were risk factors for low tumor recurrence. NLR > 2.81 was significantly associated with poor OS and tumor recurrence in the total patient population (both P < 0.001), as well as in the subgroups of patients in BCLC stages 0/A or B (all P < 0.05). Moreover, those with high NLR were associated with low OS (P = 0.027), and also with slightly higher tumor recurrence than those with low NLR for the subgroups in BCLC stage B (P = 0.058). Neither association, however, was observed among patients with BCLC stage C disease.NLR may be an independent predictor of low OS and tumor recurrence after potentially curative HR in HCC patients in BCLC stages 0/A or B.     

Long-term survival and recurrence after curative resection for hepatocellular carcinoma in patients with chronic hepatitis C virus infection: a multicenter observational study from China

BackgroundHepatocellular carcinoma (HCC) is a recognized sequalae of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. This study aimed to identify long-term survival and prognostic factors after curative resection for HCC among patients with chronic HCV infection.MethodsFrom a Chinese multicenter database, the data of consecutive patients with HCV infection undergoing curative liver resection for initial HCC between 2006 and 2015 were retrospectively reviewed. Postoperative 30-day mortality and morbidity, long-term overall survival (OS) and recurrence-free survival (RFS) were evaluated.ResultsAmong 382 HCC patients with HCV infection, 68 (18%) had concurrent HBV infection and 110 (29%) had portal hypertension. Postoperative 30-day morbidity and mortality rates were 45% and 2.9%, respectively. The 5-year OS and RFS rates were 45% and 34%, respectively. Multivariable Cox-regression analyses identified that concurrent HBV infection, presence of portal hypertension, largest tumor size > 5 cm, and macrovascular and microvascular invasion were independently associated with worse OS and RFS, while postoperative regular anti-HCV therapy was independently associated with better OS.ConclusionLong-term prognosis after HCC resection among patients with HCV infection was worse in those with concurrent HBV infection and concomitant portal hypertension. Postoperative regular anti-HCV therapy was associated with better OS.     

Assessment of the correlation between serum prolidase and alpha-fetoprotein levels in patients with hepatocellular carcinoma

AIM: To determine the predictive value of increased prolidase activity that reflects increased collagen turnover in patients with hepatocellular carcinoma(HCC).METHODS: Sixty-eight patients with HCC(mean age of 69.1 ± 10.1), 31 cirrhosis patients(mean age of59.3 ± 6.3) and 33 healthy volunteers(mean age of51.4 ± 12.6) were enrolled in this study. Univariate and multivariate analysis were used to evaluate the association of serum α-fetoprotein(AFP) values with HCC clinicopathological features, such as tumor size,number and presence of vascular and macrovascular invasion. The patients with HCC were divided into groups according to tumor size, number and presence of vascular invasion(diameters; ≤ 3 cm, 3-5 cmand ≥ 5 cm, number; 1, 2 and ≥ 3, macrovascular invasion; yes/no). Barcelona-clinic liver cancer(BCLC)criteria were used to stage HCC patients. Serum samples for measurement of prolidase and alphafetoprotein levels were kept at-80 ℃ until use.Prolidase levels were measured spectrophotometrically and AFP concentrations were determined by a chemiluminescence immunometric commercial diagnostic assay.RESULTS: In patients with HCC, prolidase and AFP values were evaluated according to tumor size, number,presence of macrovascular invasion and BCLC staging classification. Prolidase values were significantly higher in patients with HCC compared with controls(P 0.001). Prolidase levels were significantly associated with tumor size and number(P 0.001, P = 0.002,respectively). Prolidase levels also differed in patients in terms of BCLC staging classification(P 0.001).Furthermore the prolidase levels in HCC patients showed a significant difference compared with patients with cirrhosis(P 0.001). In HCC patients grouped according to tumor size, number and BCLC staging classification, AFP values differed separately(P = 0.032,P = 0.038, P = 0.015, respectively). In patients with HCC, there was a significant correlation(r = 0.616; P 0.001) between prolidase and AFP values in terms of tumor size, number and BCLC staging classification,whereas the presence of macrovascular invasion did not show a positive association with serum prolidase and AFP levels.CONCLUSION: Considering the levels of both serum prolidase and AFP could contribute to the early diagnosing of hepatocellular carcinoma.     

The effectiveness of radiofrequency ablation for patients with BCLC B1 stage hepatocellular carcinoma downgraded by transarterial chemoembolization

PurposeTo evaluate the effectiveness of radiofrequency ablation (RFA) as a curative therapy for BCLC B1 stage (beyond Milan criteria but within up-to-seven criteria) hepatocellular carcinoma (HCC) followed by downstageing by using transarterial chemoembolization (TACE).MethodsWe retrospectively recruited patients underwent RFA alone and who underwent RFA following downstaging into BCLC B1 stage using TACE between April 2011 and August 2017. Overall survival (OS) and recurrence-free survival (RFS) were compared using the Kaplan-Meier method. A propensity score analysis was performed to reduce potential bias.ResultsThe downstaging TACE+RFA and RFA alone group comprised 50 and 110 patients, respectively. After propensity score matching, the 1-, 2-, and 3-year OS rates were 100%, 92%, 74%, respectively, the 1-, 2-, and 3-year RFS rates were 40%, 36%, and 20%, respectively, for patients in the downstaging TACE+RFA group. The 1-, 2-, and 3-year OS rates were 96%, 90%, and 82%, respectively, the 1-, 2-, and 3-year RFS rates were 51%, 32%, and 32%, respectively, for patients in the RFA group. No statistical differences were observed between the two groups in terms of OS and RFS before and after matching.ConclusionRFA after downstaging into BCLC B1 stage using TACE offered a safe and effective treatment regime for patients with HCC beyond the up-to-seven criteria. The intermediate-term OS and RFS of RFA following downstaging into BCLC B1 stage using TACE for HCC were similar to that of patients who were initially in BCLC B1stage.     

Pathologic complete response to chemoembolization improves survival outcomes after curative surgery for hepatocellular carcinoma: predictive factors of response

BackgroundWe identified the predictive factors and prognostic significance of transarterial chemoembolization (TACE) for achieving pathologic complete response (pCR) before curative surgery for hepatocellular carcinoma (HCC) in hepatitis B–endemic areas.MethodsAmong 753 HCC patients treated with surgery, 124 patients underwent preoperative TACE before liver resection (LR), and 166 before liver transplantation (LT) between 2005 and 2016. Overall survival (OS) and recurrence-free survival (RFS) were analyzed. Pathologic response (PR) was defined as the mean percentage of necrotic area, and pCR was defined as the absence of viable tumor.ResultsA total of 34 (27%) and 38 (23%) patients had pCR before LR and LT, respectively. Alpha-fetoprotein (AFP) < 100 ng/mL and single tumor were significant preoperative predictors of pCR. OS and RFS were significantly improved in patients with pCR or a PR ≥ 90%, but not in patients with PR ≥ 50% after LR and LT. On multivariate analyses, PR ≥ 90% remained an independent predictor of better OS and RFS in LR and LT groups.ConclusionOverall, our data clearly demonstrate that pCR predicts favorable prognosis after curative surgery for HCC, and predictors of pCR are AFP <100 ng/mL and single tumor.     

Post-transplant infection improves outcome of hepatocellular carcinoma patients after orthotopic liver transplantation

BACKGROUND Tumor recurrence after orthotopic liver transplantation(OLT) remains a serious threat for long-term survival of the recipients with hepatocellular carcinoma(HCC), since very few factors or measures have shown impact on overcoming HCC recurrence after OLT. Postoperative infection suppresses tumor recurrence and improves patient survival in lung cancer and malignant glioma probably via stimulating the immune system. Post-transplant infection(PTI), a common complication, is deemed to be harmful for the liver transplant recipients from a short-term perspective. Nevertheless, whether PTI inhibits HCC recurrence after OLT and prolongs the long-term survival of HCC patients needs to be clarified.AIM To investigate the potential influence of PTI on the survival and tumor recurrence of patients with HCC after OLT.METHODSA total of 238 patients with HCC who underwent OLT between August 2002 and July 2016 at our center were retrospectively included and accordingly subdivided into a PTI group(53 patients) and a non-PTI group(185 patients). Univariate analyses, including the differences of overall survival(OS), recurrence-free survival(RFS), and post-recurrence survival(PRS), between the PTI and non-PTI subgroups as well as survival curve analysis were performed by the KaplanMeier method, and the differences were compared using the log rank test. The variables with a P-value 0.1 in univariate analyses were included in the multivariate survival analysis by using a Cox proportional-hazards model.RESULTS The 1-, 3-, and 5-year OS and RFS rates of the whole cohort were 86.6%, 69.0%,and 63.6%, and 75.7%, 60.0%, and 57.3%, respectively. The 1-, 3-, and 5-year OS rates for the PTI patient group(96.0%, 89.3%, and 74.0%) were significantly higher than those for the non-PTI group(84.0%, 63.4%, and 60.2%)(P = 0.033).The absence of PTI was an independent risk factor for dismal OS(relative risk[RR] = 2.584, 95%CI: 1.226-5.449) and unfavorable RFS(RR = 2.683, 95%CI: 1.335-5.390). Subgroup analyses revealed that PTI remarkably improved OS(P = 0.003)and RFS(P = 0.003) rates of HCC patients with vascular invasion(IV), but did not impact on OS(P = 0.404) and RFS(P = 0.304) of patients without VI. Among the patients who suffered post-transplant tumor recurrence, patients with PTI showed significantly better OS(P = 0.026) and PRS(P = 0.042) rates than those without PTI.CONCLUSION PTI improves OS and RFS of the transplant HCC patients at a high risk for posttransplant death and tumor recurrence, which is attributed to suppressive effect of PTI on HCC recurrence.     

Preoperative transarterial chemoembolization for barcelona clinic liver cancer stage A/B hepatocellular carcinoma beyond the milan criteria: a propensity score matching analysis

BackgroundDebate continues about the benefits of preoperative transarterial chemoembolization (TACE) for treatment of hepatocellular carcinoma (HCC). This study aimed to assess the impact of preoperative TACE on long-term outcomes after curative resection for HCC beyond the Milan criteria.MethodsPatients who underwent HCC resection exceeding the Milan criteria without macrovascular invasion between 2015 and 2018 were identified (n = 393). Short- and long-term outcomes were compared between patients who underwent preoperative TACE and patients who did not before and after propensity score matching (PSM). Factors associated with recurrence after resection were analyzed.Results100 patients (25.4%) underwent preoperative TACE. Recurrence-free survival (RFS) and overall survival (OS) were comparable with patients who underwent primary liver resection. 7 patients (7.0%) achieved total necrosis with better RFS compared with patients who had an incomplete response to TACE (P=0.041). PSM created 73 matched patient pairs. In the PSM cohort, preoperative TACE improved RFS (P=0.002) and OS (P=0.003). The maximum preoperatively diagnosed tumor diameter (HR 3.230, 95% CI: 1.116–9.353; P=0.031) and hepatitis B infection (HR 2.905, 95%CI: 1.281–6.589; P=0.011) were independently associated with favorable RFS after HCC resection.ConclusionPreoperative TACE made no significant difference to perioperative complications and was correlated with an improved prognosis after surgical resection for patients with HCC beyond the Milan criteria.     

Do the existing staging systems for primary liver cancer apply to combined hepatocellular carcinoma-intrahepatic cholangiocarcinoma?

Background:The incidence of combined hepatocellular carcinoma-intrahepatic cholangiocarcinoma(c HCC-ICC) is relatively low,and the knowledge about the prognosis of c HCC-ICC remains obscure.In the study,we aimed to screen existing primary liver cancer staging systems and shed light on the prognosis and risk factors for c HCC-ICC.Methods:We retrospectively reviewed 206 c HCC-ICC patients who received curative surgical resection from April 1999 to March 2017.The correlation of survival measures with the histological types or with tumor staging systems was determined and predictive values of tumor staging systems with c HCC-ICC prognosis were compared.Results:The histological type was not associated with overall survival(OS)(P = 0.338) or disease-free survival(DFS)(P = 0.843) of patients after curative surgical resection.BCLC,TNM for HCC,and TNM for ICC stages correlated with both OS and DFS in c HCC-ICC(all P 0.05).The predictive values of TNM for HCC and TNM for ICC stages were similar in terms of predicting postoperative OS(P = 0.798) and DFS(P = 0.191) in c HCC-ICC.TNM for HCC was superior to BCLC for predicting postoperative OS(P = 0.022) in c HCC-ICC.Conclusion:The TNM for HCC staging system should be prioritized for clinical applications in predicting c HCC-ICC prognosis.     

Patterns,treatments, and prognosis of tumor recurrence after resection for hepatocellular carcinoma with microvascular invasion: a multicenter study from China

BackgroundMicrovascular invasion (MVI) is a risk factor of post-hepatectomy tumor recurrence for hepatocellular carcinoma (HCC). The patterns, treatments, and prognosis have not been documented in HCC patients with MVI.MethodsA multicenter database of patients with HCC and MVI following resection was analyzed. The clinicopathological and initial operative data, timing and first sites of recurrence, recurrence management, and long-term survival outcomes were analyzed.ResultsOf 1517 patients included, the median follow-up was 39.7 months. Tumor recurrence occurred in 928 patients, with 49% within 6 months of hepatectomy and 60% only in the liver. The incidence of intrahepatic only recurrence gradually increased with time after 6 months. Patients who developed recurrence within 6 months of hepatectomy had worse survival outcomes than those who developed recurrence later. Patients who developed intrahepatic only recurrence had better prognosis than those with either extrahepatic only recurrence or those with intra- and extrahepatic recurrence. Repeat resection of recurrence with curative intent resulted in better outcomes than other treatment modalities.ConclusionPost-hepatectomy tumor recurrence in patients with HCC and MVI had unique characteristics and recurrence patterns. Early detection of tumor recurrence and repeat liver resection with curative intent resulted in improved long-term survival outcomes.     

Hepatocellular carcinoma ≤ 4 cm treated with radiofrequency ablation with or without percutaneous ethanol injection

Background. To compare the survival of Chinese cirrhotic patients with hepatocellular carcinoma (HCC) ≤ 4 cm who underwent radiofrequency ablation (RFA) alone or a combination of RFA with percutaneous ethanol injection (PEI).Material and methods. Retrospective analysis was performed for 681 cases with HCC ≤ 4 cm who were treated with RFA alone or RFA combined with PEI (RFA + PEI) between 2004 and 2011.Results. As a result, 180 patients in each group were selected after propensity score matching (PSM). Higher overall survival (OS) and recurrence-free survival (RFS) rates were achieved by RFA + PEI compared with RFA alone (P = 0.019 and 0.009, respectively). The 1-, 3-, and 5-year cumulative OS rates were 78.0, 44.4, and 30.1% for patients in RFA group and 88.2, 58.0, and 41.1% for patients in RFA + PEI group, respectively. Besides, the 1-, 3-, and 5-year cumulative RFS rates were 77.0, 43.8, and 29.2% in RFA group, and 87.9, 57.6, and 38.4% in RFA + PEI group, respectively. The local recurrence, complete ablation and five-year mortality showed no distinct differences between RFA and RFA + PEI groups in three subgroups classified with tumor size. Moreover, Cox regression multivariate analysis results showed that sex and treatment approach were significantly related to OS, whereas sex, status of HBsAg, local recurrence, and number of tumor nodule were related to RFS.Conclusion. Therefore, the combination of RFA and PEI yielded better OS and RFS rates than RFA alone for Chinese patients with HCC ≤ 4 cm.     

Liver transplantation for hepatocellular carcinoma: the impact of human immunodeficiency virus infection

Liver transplantation (LT) has become an accepted therapy for end-stage liver disease in human immunodeficiency virus-positive (HIV+) patients, but the specific results of LT for hepatocellular carcinoma (HCC) are unknown. Between 2003 and 2008, 21 HIV+ patients and 65 HIV- patients with HCC were listed for LT at a single institution. Patient characteristics and pathological features were analyzed. Univariate analysis for overall survival (OS) and recurrence-free survival (RFS) after LT was applied to identify the impact of HIV infection. HIV+ patients were younger than HIV- patients [median age: 48 (range = 41-63 years) versus 57 years (range = 37-72 years), P < 0.001] and had a higher alpha-fetoprotein (AFP) level [median AFP level: 16 (range = 3-7154 μg/L] versus 13 μg/L (range = 1-552 μg/L), P = 0.04]. There was a trend toward a higher dropout rate among HIV+ patients (5/21, 23%) versus HIV- patients (7/65, 10%, P = 0.08). Sixteen HIV+ patients and 58 HIV- patients underwent transplantation after median waiting times of 3.5 (range = 0.5-26 months) and 2.0 months (range = 0.5-24 months, P = 0.18), respectively. No significant difference was observed in the pathological features of HCC. With median follow-up times of 27 (range = 5-74 months) and 36 months (range = 3-82 months, P = 0.40), OS after LT at 1 and 3 years reached 81% and 74% in HIV+ patients and 93% and 85% in HIV- patients, respectively (P = 0.08). RFS rates at 1 and 3 years were 69% and 69% in HIV+ patients and 89% and 84% in HIV- patients, respectively (P = 0.09). In univariate analysis, HIV status did not emerge as a prognostic factor for OS or RFS. CONCLUSION: Because of a higher dropout rate among HIV+ patients, HIV infection impaired the results of LT for HCC on an intent-to-treat basis but had no significant impact on OS and RFS after LT.