Expanded criteria for hepatocellular carcinoma through down-staging prior to liver transplantation: not yet there

The accepted treatment strategy for hepatocellular carcinoma (HCC) is supported by randomized controlled trials (RCTs), meta-analysis, and large cohort studies. For instance, the Milan criteria applied for indicating liver transplantation have been validated by several cohort studies including more than 1000 patients. Regarding medical treatments, approximately 80 RCTs have been published so far in HCC. These studies provide the evidence to support chemoembolization as the treatment for patients at intermediate stage (meta-analysis of 6 RCTs) and show the lack of benefit of tamoxifen assessed in 12 RCTs including more than 1500 patients. In this scenario, what is the evidence to advocate for the expansion of HCC criteria through down-staging prior to liver transplantation? Such an approach has never been tested through RCTs or even well-designed cohort studies including enough patients and adequate follow-up. Only a few small studies with heterogeneous target populations and treatments applied are available. The results of these studies are inconsistent and do not provide compelling evidence to accept down-staging as a standard of care.     

Circulating DNA level is negatively associated with the long-term survival of hepatocellular carcinoma patients

AIM: To quantify the circulating DNA in plasma from patients with hepatocellular carcinoma (HCC) and to evaluate its prognostic value. METHODS: Blood samples were collected from 79 patients with HCC before operation, 20 patients with liver cirrhosis, and 20 healthy volunteers. Circulating DNA was extracted from plasma and quantified. The association between circulating DNA level and prognosis of HCC patients was evaluated. RESULTS: Compared with the healthy volunteers (17.6±9.5 ng/mL), a significant higher circulating DNA level was found in the patients with HCC (47.1±43.7 ng/ mL, P = 0.000) or with liver cirrhosis (30.0±13.3 ng/ mL, P - 0.002). The circulating DNA level was closely associated with tumor size (P = 0.008) and TNM stage (P = 0.040), negatively associated with the 3-year disease-free survival (DFS) (P - 0.017) and overall survival (OS) (P = 0.001). CONCLUSION: Large or invasive tumor may release more circulating DNA, and higher level of circulating DNA may be associated with poor prognosis of HCC patients.     

High expressions of vascular endothelial growth factor and platelet-derived endothelial cell growth factor predict poor prognosis in alpha-fetoprotein-negative hepatocellular carcinoma patients after curative resection

Purpose  To evaluate the prognosis value of vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) in alpha-fetoprotein (AFP)-negative hepatocellular carcinoma (HCC) patients after curative resection. Methods  Tumor tissue microarrays (TMAs) were used to detect the expressions of VEGF and PD-ECGF in consecutive 162 AFP-negative HCC patients undergoing curative resection between 1997 and 2000 in our institute. Clinicopathologic data for these patients were evaluated. The prognostic significance was assessed using Kaplan–Meier survival estimates and log-rank tests. Multivariate study with Cox’s proportional hazard model was used to evaluate the prognosis-related aspects. Results  The positive rates of VEGF and PD-ECGF in tumor tissues were 59.9% (97/162) and 62.3% (101/162), respectively. Univariate analysis showed that VEGF and PD-ECGF were prognostic factors for relapse-free survival (P = 0.034 and P = 0.033, respectively). Multivariate analyses demonstrated that the co-index (VEGF/PD-ECGF) was an independent prognostic factor for overall survival and relapse-free survival (P = 0.002 and P = 0.000, respectively). Conclusion  The co-index of VEGF and PD-ECGF is a promising independent predictor for recurrence and survival of AFP-negative HCC patients after curative resection. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. J. Hu, Y. Xu and Z.-Z. Shen have contributed equally to this work.     

Intrahepatic cholangiocarcinoma: report of 272 patients compared with 5,829 patients with hepatocellular carcinoma

Purpose  To clarify clinicopathologic differences between patients with intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC), and identify potential factors influencing survival after hepatectomy for ICC. Methods  Comparison of clinicopathologic data was made between patients who underwent hepatectomy for ICC (n = 272) and HCC (n = 5,829) during the same period. Twenty-five clinicopathologic variables were selected for univariate and multivariate analyses to evaluate their influence on prognosis of ICC. Results  Compared with patients with HCC, ICC patients were more common in females and more elderly, had a lower proportion of asymptomatic tumors, lower serum alpha-fetoprotein, higher serum carcinoembryonic antigen, carbohydrate antigen 19–9 and alkaline phosphatase levels; lower incidence of hepatitis history, associated cirrhosis and serum hepatitis B surface antigen; lower proportion of small tumors, well-encapsulated tumors and tumor emboli in the portal vein; higher proportion of single tumor, perihila lymph node involvement and poor differentiation; and less frequency of limited resection (all, P < 0.0001). Distant metastasis was less frequent in patients with ICC (P = 0.027). A total of 5-years overall and disease-free survival (in brackets) after resection was 26.4% (13.1%) and 44.5% (33.1%) (P < 0.0001, P < 0.0001) for patients with ICC and HCC, respectively. Factors influencing survival after resection of ICC can be divided mainly into two categories: early detection of asymptomatic ICC (P < 0.0001) and curative resection (P = 0.002). Conclusion  ICC Patients have distinct clinicopathologic features as compared with HCC patients. Surgery remains the only effective treatment for ICC. Early detection of asymptomatic ICC and curative resection were the key to achieve optimal survival.     

Interventional endoscopic ultrasonography

Endoscopic ultrasonography (EUS) is the combination of endoscopy and intraluminal ultrasonography. This allows use of a high frequency transducer, which, due to the short distance to the target lesion, enables ultrasonographic images of high resolution to be obtained. Endoscopic ultrasonography is now a widely accepted modality for the diagnosis of pancreatobiliary diseases. It can be used to determine the depth of invasion of gastrointestinal malignancies, and often for visualizing lesions more precisely than other imaging modalities. The most important early limitation of EUS was the lack of specificity in the differentiation between benign and malignant changes. In 1992, EUS‐guided fine needle aspiration (EUS‐FNA) of lesions in the pancreas head has been made possible using a curved linear array echoendoscope. Since then, many researchers have expanded the indication of EUS‐FNA to various kinds of lesions and also for a variety of therapeutic purposes. In this review, we particularly focus on the present and future roles of interventional EUS, including EUS‐FNA and therapeutic EUS.     

Usefulness of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for undiagnosed intra-abdominal lymphadenopathy

Background  The differentiation between benign and malignant abdominal lymph nodes is difficult, especially if no primary site is evident or if cancer resection was remote in time. The aim of this study was to evaluate the yield of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in patients with undiagnosed intra-abdominal lymphadenopathy. Methods  Fifty-seven consecutive patients with undiagnosed abdominal lymphadenopathy who were registered in our EUS-FNA database from January 1997 to December 2007 were reviewed. EUS-FNA was carried out using a 22-G needle. The final pathological diagnosis was based on the cytopathological, histological, and immunohistochemical (IHC) findings. Results  Adequate specimens were obtained in 93% cases. The final diagnoses included local recurrence of malignancy after resection (n = 16), lymphoma (n = 12), and benign/reactive changes (n = 17). The sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of EUS-FNA were 94, 100, 100, 90 and 96%, respectively. In addition, it was also possible to classify lymphoma subtypes in 83% of cases. No complications occurred during the procedures. Conclusions  EUS-FNA is clinically very useful for establishing the diagnosis of abdominal lymphadenopathy of unknown cause and can provide sufficient tissue for IHC and subtyping of lymphomas.