Xiaobin Feng

Perspectives on using des-γ-carboxyprothrombin (DCP) as a serum biomarker: facilitating early detection of hepatocellular carcinoma in China

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths in China. Evidence has shown that surgical resection and liver transplantation may offer the best potential for treating HCC but are only available to patients whose tumors are detected early. Over the past few decades, although a series of measures for standardized management of HCC has been implemented in China, most patients with HCC in China still present with advanced-stage disease, thus strategies to screen for and diagnose HCC at an earlier stage are urgently needed in China when curable interventions can be offered to achieve long-term disease-free survival for patients with HCC. In China, the serum biomarker α-fetoprotein (AFP) is considered a useful and feasible tool for HCC screening and early diagnosis. However, the sensitivity and specificity of AFP vary widely, and the total AFP is not always specific, especially when HCC is in its early stages. Globally, numerous studies have reported that the combination of des-γ-carboxyprothrombin (DCP) and AFP may have a higher sensitivity than AFP alone, and suggested DCP could also be used to assess the progression of HCC. However, DCP has not been approved in China until now. Differ from most of Western countries, people with HBV infection are the largest population at risk of developing HCC China. In order to assess the screening and diagnostic value of DCP in Chinese patients with HCC, a first large-scale, multi-center study was launched in China in 2012, results showed that DCP can help to detect HCC in its early stages and facilitate definitive treatment. The clinical use of DCP is urgently needed to facilitate early detection of HCC in China.

Short- and long-term outcomes of hepatectomy with or without radiofrequency-assist for the treatment of hepatocellular carcinomas: a retrospective comparative cohort study

The objective of this study was to compare the short- and long-term outcomes of radiofrequency-assisted liver resection (RFLR) and conventional clamp-crushing liver resection (CCLR) and to evaluate the safety and efficiency of RFLR. Between January 2008 and December 2012, a total of 597 patients with hepatocellular carcinoma (HCC) who underwent curative hepatectomy were identified. A total of 272 patients underwent RFLR, and 325 patients received CCLR. The short- and long-term outcomes were compared. The patients in the RFLR and CCLR groups showed similar baseline characteristics. The RFLR group showed less intraoperative blood loss (485.5 vs. 763.2 mL, p = 0.003), a lower transfusion requirement rate (19.1 vs. 31.7%, p ≤ 0.01), shorter surgery duration (211 vs. 296 min, p ≤ 0.01) and a lower vascular inflow occlusion rate (25.7 vs. 33.8%, p = 0.032). No significant postoperative changes in bilirubin or liver enzymes were observed in the two groups. The degree of postoperative complications and morbidity did not significantly differ between the two groups. There were no significant differences in the 1-, 2- and 3-year overall survival rates (73.8%, 58.5%, and 55.7% vs. 80.8%, 65.8%, and 56.2%, respectively) or disease-free rates (51.9%, 47.2%, and 46.0% vs. 54.5%, 44.9%, and 38.5%, respectively) between the RFLR and CCLR groups. These results suggested RFLR was a safe and efficient method for patients with HCC. RFLR was associated with decreased blood loss, fewer blood transfusions, shorter surgery times and less vascular inflow occlusion application. The RFLR group did not show increased liver injury or postoperative morbidity or mortality.

Classification and management of hepatolithiasis: A high-volume, single-center's experience

Hepatolithiasis is endemic to East Asia, but immigration from the region means that this rare but emerging disease will pose a therapeutic challenge to doctors in the West as well. Curative management of hepatolithiasis is difficult since its etiology has not been fully elucidated. Hepatectomy is the best approach to treating hepatolithiasis. Here, we propose a novel classification of hepatolithiasis and describe features of each type. We then relate our experience with various forms of hepatectomy to treat different types of hepatolithiasis. Surgery should be indicated for all cases of hepatolithiasis. The proposed classification will help to determine surgical strategies. Better selection of which patients should undergo a hepatectomy will lead to better outcomes.

LPS Increases MUC5AC by TACE/TGF-α/EGFR Pathway in Human Intrahepatic Biliary Epithelial Cell

Background. Mucin 5AC (MUC5AC) overproduction plays important roles in stone formation and recurrence of hepatolithiasis. We aim to investigate the involved mechanism and the potential target to block this process. Methods. 42 bile duct samples from hepatolithiasis and 15 normal bile duct samples from hemangioma patients were collected for detecting MUC5AC expression by immunohistochemistry. MUC5AC and phosphoepidermal growth factor receptor (pEGFR) expressions in human intrahepatic biliary epithelial cells (HIBECs) cultured with or without lipopolysaccharide (LPS) were detected by real-time PCR and western blot analysis. Transforming growth factor-α (TGF-α) secretion in HIBECs was detected by ELISA. Results. MUC5AC was overexpressed in bile ducts of hepatolithiasis samples compared with bile ducts from hemangioma samples. LPS upregulated MUC5AC expression in HIBECs. LPS promoted EGFR activation, and inhibiting EGFR activation by AG1478 significantly decreased LPS-induced MUC5AC overexpression in HIBECs. Moreover, LPS increased TGF-α secretion, and inhibiting tumor necrosis factor-α converting enzyme (TACE), which has been implicated in ectodomain cleavage of TGF-α, significantly inhibited LPS-induced EGFR activation and subsequent MUC5AC overexpression in HIBECs. Conclusion. Our results suggested that LPS increases MUC5AC expression through the TACE/TGF-α/EGFR pathway in HIBECs. This new finding might give light to the prevention of stone formation and recurrence of hepatolithiasis.

Predictive value of indocyanine green retention rate with respect to complications of radiofrequency ablation in 878 patients with hepatocellular carcinoma.

Abstract Background and aims: Radiofrequency ablation (RFA) is a minimally invasive technique used for the treatment of hepatocellular carcinoma (HCC). It may produce complications. The indocyanine green (ICG) retention rate at 15 min (ICGR15) has been used to predict complications after hepatectomy. In this study, the prediction of the value of ICGR15 for complications of RFA to the patients with HCC was evaluated. Methods: Some 878 cases of HCC treated between June 2009 and June 2013 were evaluated. All patients were treated by percutaneous radiofrequency ablation. Patients were divided into two groups: a complication group (85 cases) and a complication-free group (793 cases). ICGR15 and other baseline characteristics of the two groups were compared. A logistic regression model was used to analyse the merits of assessing liver reserve to predict complications post-RFA. Results: Complications such as intra-abdominal haemorrhage and pleural effusion occurred in 85 (9.68%) patients after RFA. Patients in the two groups did not differ with regard to baseline parameters. Patients in the two groups did differ significantly in ICGR15 and tumour site (p < 0.05). Tumour site was found to have a significant impact on the rate of complications post-RFA. There was no significant difference in ICGR15 values among patients with the same Child-Pugh scores or in the same tumour site. Conclusions: The present results demonstrated that RFA is minimally invasive and suitable for the treatment of HCC. They also showed that ICGR15 did not independently predict for liklihood of post-RFA complications, after controlling for tumour site. Patients with tumours located subcapsularly or near the porta hepatis were found to have significantly higher rates of post-operative complications after RFA than to patients with tumours in the liver parenchyma.

Safety and efficacy of radiofrequency-assisted ALPPS (RALPPS) in patients with cirrhosis-related hepatocellular carcinoma

Abstract Background and aims: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has high morbidity and mortality. In this study, the safety and efficacy of a modification of ALPPS (radiofrequency-assisted ALPPS, RALPPS) were assessed in patients with hepatocellular carcinoma (HCC). Materials and methods: Patients who were diagnosed with HCC and were considered to have an insufficient future liver remnant (FLR) were enrolled. In stage I, a radiofrequency ablation (RFA) device was used to cauterise along the planned transection plane to form a coagulum avascular area. When the FLR reached above 40%, hepatectomy was performed in stage II along the coagulum area established previously. After two stages, operative morbidity, mortality, per cent increase in FLR, operative time and blood loss were evaluated. Results: Between July 2014 and September 2015, 10 patients with HCC (9 with hepatitis-related cirrhosis) were treated with the RALPPS procedure. The incidence of severe complications (Clavien-Dindo ≥ IIIb) was 20% (2/10). One patient died. No biliary leakage, intraperitoneal infection or post-hepatectomy liver failure (PHLF) occurred after both stages. The median FLR before stage I was 31% (364 ml). This increased to 47% (632 ml) before stage II after a median interval of 28 days. The median percentage increase in FLR was 53% (210 ml). Additionally, the median operative time during the first and second stages was 214 and 281 min, respectively. The corresponding median blood loss was 200 and 550 ml, respectively. Conclusions: RALPPS has a potential advantage in eliminating serious complications of biliary leakage and PHLF associated with classic ALPPS. On the basis of rigorous patient selection criteria, RALPPS may achieve the same effect of promoting significant growth of the FLR in patients with cirrhosis-related HCC and insufficient FLR volume, albeit at the cost of a longer interval time.

Biomarkers: evaluation of clinical utility in surveillance and early diagnosis for hepatocellular carcinoma.

Abstract Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second most common cause of death from cancer worldwide. Strategies to surveil and diagnose HCC in an earlier stage are urgently needed since this is when curable interventions can be offered to achieve long-term disease-free survival. Over the past few decades, research has suggested measuring alpha-fetoprotein (AFP) concentration and performing abdominal ultrasound (US) as part of routine surveillance of HCC every 6 months for high-risk patients, and many HCC guidelines worldwide have also recommended these examinations. Over the past 5 years, however, the role of serum biomarkers in HCC surveillance and diagnosis has diminished due to advances in imaging modalities. AFP was excluded from the surveillance and/or diagnostic criteria in the HCC guidelines published by some Western countries. In Asian countries, serum biomarkers such as AFP, the Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and des-γ-carboxyprothrombin (DCP) are still recommended for HCC surveillance and are being used as an adjunctive diagnostic tool in accordance with HCC guidelines. Moreover, novel biomarkers including Dickkopf-1 (DKK1), midkine (MDK), and microRNA (miRNA) are being studied in this regard. China accounts for 50% of HCC cases worldwide, so identifying biomarkers of HCC is paramount. Recent studies have indicated the clinical utility of simultaneous measurement of AFP and DCP for the early detection of HCC in China. They are predominantly used for cases caused by HBV infection. Additional large-scale prospective studies should be conducted to establish the utility of these biomarkers.

Des-γ-Carboxyprothrombin Plasma Level in Diagnosis of Hepatocellular Carcinoma in a Chinese Population Undergoing Surgery

Background The usefulness of Des-γ-carboxyprothrombin (DCP) has been indicated in areas where hepatitis C virus is prevalent. DCP has yet to be used in China. The aim of this study was to evaluate the usefulness of DCP in Chinese patients with hepatocellular carcinoma (HCC) predominantly caused by hepatitis B. Material/Methods 329 subjects with HCC and 371 subjects without HCC that all underwent surgery were consecutively enrolled. Serum AFP and plasma DCP levels in all subjects and 153 healthy volunteers were measured and analyzed. Results Of 329 subjects with HCC, 258 (78.4%) were HBsAg positive. The median level of plasma DCP was 853.72 mAU/mL in subjects with HCC, 26.43 mAU/mL in subjects without HCC, and 29.91 m AU/mL in healthy volunteers. A cut-off DCP value of 87 mAU/mL yielded the optimal sensitivity of 74.80% and a specificity of 83.33% for differentiating subjects with HCC from subjects without HCC. The combination of AFP of 21.33 ng/mL and DCP of 87 mAU/mL had a sensitivity of 82.60% for tumors no larger than 2 cm, as well as a sensitivity of 90% for tumors larger than 5 cm. Conclusions The combination of DCP and AFP yielded great improvement in sensitivity in differentiating subjects with HCC from subjects without HCC. These two markers may be incorporated in the protocol for surveillance and diagnosis of HCC in the high-risk Chinese population.