Yan-Yan Wang

Hepatic Resection as a Safe and Effective Treatment for Hepatocellular Carcinoma Involving a Single Large Tumor, Multiple Tumors, or Macrovascular Invasion

AbstractThis systematic review examined whether the available evidence justifies using hepatic resection (HR) during later stages of hepatocellular carcinoma (HCC), which contravenes treatment guidelines but is current practice at many medical centers.Official guidelines and retrospective studies recommend different roles for HR for patients with large/multinodular HCC or with HCC involving macrovascular invasion (MVI).Several databases were systematically searched for studies examining the safety and efficacy of HR for treating HCC involving a single large tumor (>5 cm) or multiple tumors, or for treating HCC involving MVI.We identified 50 studies involving 14 808 patients that investigated the use of HR to treat large/multinodular HCC, and 24 studies with 4389 patients that investigated HR to treat HCC with MVI. Median in-hospital mortality for patients with either type of HCC was significantly lower in Asian studies (2.7%) than in non-Asian studies (7.3%, P < 0.001). Median overall survival (OS) was significantly higher for all Asian patients with large/multinodular HCC than for all non-Asian patients at both 1 year (81% vs 65%, P < 0.001) and 5 years (42% vs 32%, P < 0.001). Similar results were obtained for median disease-free survival at 1 year (61% vs 50%, P < 0.001) and 5 years (26% vs 24%, P < 0.001). However, median OS was similar for Asian and non-Asian patients with HCC involving MVI at 1 year (50% vs 52%, P = 0.45) and 5 years (18% vs 14%, P = 0.94). There was an upward trend in 5-year OS in patients with either type of HCC.HR is reasonably safe and effective at treating large/multinodular HCC and HCC with MVI. The available evidence argues for expanding the indications for HR in official treatment guidelines.

Albumin-bilirubin versus Child-Pugh score as a predictor of outcome after liver resection for hepatocellular carcinoma.

The Child–Pugh (CP) score is used widely to assess liver function and predict postoperative outcomes in patients with hepatocellular carcinoma (HCC). Recently, the albumin–bilirubin (ALBI) score has been validated as a predictor of overall survival in these patients. This study aimed to compare the ability of the ALBI and CP scores to predict outcomes in patients with HCC after liver resection with curative intent.

Hepatic resection is safe and effective for patients with hepatocellular carcinoma and portal hypertension.

Background & Aims Official guidelines do not recommend hepatic resection (HR) for patients with hepatocellular carcinoma (HCC) and portal hypertension (PHT). This study aims to investigate the safety and efficacy of HR for patients with HCC and PHT. Methods Mortality and survival after HR were analyzed retrospectively in a consecutive sample of 1738 HCC patients with PHT (n = 386) or without it (n = 1352). To assess the robustness of findings, we repeated the analysis using propensity score-matched analysis. We also comprehensively searched the PubMed database for studies evaluating the efficacy and safety of HR for patients with HCC and PHT. Results The 90-day mortality rate was 6.7% among those with PHT and 2.1% among those without it (P<.001). Patients without PHT had a survival benefit over those with PHT at 1, 3, and 5 years (96% vs 90%, 75% vs 67%, 54% vs 45%, respectively; P = .001). In contrast, PHT was not associated with worse short- or long-term survival when only propensity score-matched pairs of patients and those with early-stage HCC or those who underwent minor hepatectomy were included in the analysis (all P>.05). Moreover, the recurrence rates were similar between the two groups. Consistent with our findings, all 9 studies identified in our literature search reported HR to be safe and effective for patients with HCC and PHT. Conclusions HR is safe and effective in HCC patients with PHT and preserved liver function. This is especially true for patients who have early-stage HCC or who undergo minor hepatectomy.

Liver resection for patients with hepatocellular carcinoma and macrovascular invasion, multiple tumours, or portal hypertension

Sir, We read with great interest the leading article by Bruix et al 1 published in Gut . This article recommended palliative treatments for patients with hepatocellular carcinoma (HCC) involving macrovascular invasion, multiple tumours, or portal hypertension. With better patient selection and improvement of perioperative care, liver resection (LR) offers the most consistent and clinically meaningful long-term survival in HCC over the past 20 years, which has been documented by both Eastern and Western centres.2 ,3 However, Western official guidelines do not recommend LR for treating intermediate and advanced stage HCC.4 ,5 Here, we systematically searched PubMed database for studies investigating the safety and efficacy of LR for treating patients with HCC involving macrovascular invasion, multiple tumours (≥2) or portal hypertension. We only included studies which were published in English on …

Historical Comparison of Overall Survival after Hepatic Resection for Patients With Large and/or Multinodular Hepatocellular Carcinoma.

AbstractThe present study compared the efficacy of hepatic resection (HR) in patients with large hepatocellular carcinoma (HCC) and those with multinodular tumor and examined how that efficacy has changed over time in a large medical center.The intermediate stage of HCC comprises a highly heterogeneous patient population. Moreover, official guidelines have different views on the suitability of HR to treat such patients.A consecutive sample of 927 patients with preserved liver function and large and/or multinodular HCC who were treated by initial HR were divided into 3 groups: those with a single tumor ≥5 cm in diameter (n = 588), 2 to 3 tumors with a maximum diameter >3 cm (n = 225), or >3 tumors of any diameter (n = 114). Hospital mortality and overall survival (OS) in each group were compared for the years 2000 to 2007 and 2008 to 2013.Patients with >3 tumors showed the highest incidence of hospital mortality of all groups (P < 0.05). Kaplan–Meier survival analysis showed that OS varied across the 3 groups as follows: single tumor > 2 to 3 tumors > 3+ tumors (all P < 0.05). OS at 5 years ranged from 24% to 41% in all 3 groups for the period 2000 to 2007, and from 35% to 46% for the period 2008 to 2013. OS was significantly higher during the more recent 6-year period in the entire patient population, those with single tumor, and those with 3+ tumors (all P < 0.05). However, in patients with 2 to 3 tumors, OS was only slightly higher during the more recent 6-year period (P = 0.084).Prognosis can vary substantially for these 3 types of HCC. Patients with >3 tumors show the highest hospital mortality and lowest OS after HR. OS has been improving for all 3 types of HCC at our medical center as a consequence of improvements in surgical technique and perioperative management.

Impact of diabetes mellitus on the prognosis of patients with hepatocellular carcinoma after curative hepatectomy.

Background: The influence of diabetes mellitus (DM) on the prognosis of patients with hepatocellular carcinoma (HCC) remains controversial. Here we investigated the impact of DM on the prognosis of such patients after curative hepatectomy. Methods: A consecutive cohort of 505 patients with HCC (134 with DM, 371 without) underwent curative hepatectomy were retrospectively evaluated. Postoperative morbidity and mortality, overall survival (OS) and disease-free survival (DFS) were compared between patients with or without DM. Independent prognostic predictors were identified using the Cox proportional hazards model. Results: Patients with or without DM showed similar morbidity and 30- and 90- day mortality after curative hepatectomy (all P>0.05), as well as similar DFS at 1, 3, 5 years (P = 0.781). However, the group of patients with DM showed significantly lower OS at 1, 3, 5 years than the group without DM (P = 0.038). Similar results were obtained in the propensity-matched cohort. Cox multivariate analysis identified DM as an independent predictor of poor OS, but not of poor DFS. We repeat compared OS and DFS for DM and non-DM subgroups defined according to the presence or absence of hepatitis B virus infection and cirrhosis. Similar results were obtained in all subgroups except the non-cirrhotic subgroup which showed patients with and without DM had similar OS. Conclusions: DM does not significantly affect the postoperative morbidity or mortality or the DFS of patients with HCC after curative hepatectomy. It is, however, associated with significantly lower OS, especially in patients with cirrhosis.

Intermediate-stage HCC--upfront resection can be feasible.

We read with great interest the Review by Forner et al. (Treatment of intermediate-stage hepatocellular carcinoma. Nat. Rev. Clin. Oncol. 11, 525–535; 2014),1 which focused on the definition of and treatment options for intermediate-stage hepato cellular carcinoma (HCC). Their definition appropriately accounts for the clinical hetero geneity of intermediate-stage HCC, and we applaud their recommendation that disease involving a single large tumour (>5 cm) without vascular invasion should be classified as early-stage disease,1 which contrasts with previous articles from the Barcelona Clinic Liver Cancer (BCLC) group.2 We also applaud their suggestion that patients with a single large tumour (>5 cm) and no vascular invasion can benefit from hepatic resection, when technically feasible.1 This article, written by members of the highly influential BCLC group, might help advance HCC treatment by updating diagnostic guidelines and providing tentative support for less restrictive use of hepatic resection. At the same time, the Review contains some statements regarding the treatment of intermediate-stage HCC that might not adequately reflect the available clinical evidence; these statements, in our opinion, overemphasize the appropriateness of transarterial chemoembolization (TACE) and sorafenib therapy, and severely u nderestimate the usefulness of hepatic resection. Forner et al.1 indicate that TACE should be considered as the first-line treatment option for patients with intermediate-stage HCC, and that patients for whom TACE is contraindicated or proves unsuccessful can be considered for sorafenib therapy or radioembolization. Although the authors are correct that TACE is widely accepted in clinical guidelines as the first-line therapy for patients with intermediate-stage HCC, this treatment has not been consistently associated with a survival benefit across a wide range of studies conducted in several countries. Studies demonstrating a survival benefit have compared TACE with best supportive care;3 however, no benefit has been observed Intermediate-stage HCC—upfront resection can be feasible

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

Abstract 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.

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.

Expression of P62 in hepatocellular carcinoma involving hepatitis B virus infection and aflatoxin B1 exposure

This study aims to clarify the relationship and mechanism between expression of autophagy‐related protein P62 and prognosis of patients with hepatocellular carcinoma (HCC) involving chronic hepatitis B virus (HBV) infection and aflatoxin B1 (AFB1) exposure. HCC patients who underwent resection were divided into three groups: HBV(+)/AFB1(+) (n = 26), HBV(+)/AFB1(−) (n = 68), and HBV(−)/AFB1(−) (n = 14). The groups were compared in terms of mRNA and protein levels of P62, disease‐free survival (DFS), and overall survival (OS) and the expression of NRF2, Nqo1, and AKR7A3 in P62 high‐expression and low‐expression group. HBV(+)/AFB1(+) group has lower DFS and OS, and higher P62 expression than in the other two groups. P62 expression generally correlated with elevated NRF2 and Nqo1 expression, and reduced AKR7A3 expression. Patients expressing high levels of P62 showed significantly lower DFS and OS rates than patients expressing low levels. HCC involving HBV infection and AFB1 exposure is associated with relatively high risk of tumor recurrence, and this poor prognosis may relate to high P62 expression. High P62 expression activates the NRF2 pathway, promotes tumor recurrence. The downregulation of AKR7A3 also reduced liver detoxification of aflatoxin B1.