Shuling Chen

Supersonic shearwave elastography in the assessment of liver fibrosis for postoperative patients with biliary atresia.

To explore an effective noninvasive tool for monitoring liver fibrosis of children with biliary atresia (BA) is important but evidences are limited. This study is to investigate the predictive accuracy of supersonic shearwave elastography (SSWE) in liver fibrosis for postoperative patients with BA and to compare it with aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 (FIB-4). 24 patients with BA received SSWE and laboratory tests before scheduled for liver biopsy. Spearman rank coefficient and receiver operating characteristic (ROC) were used to analyze data. Metavir scores were F0 in 3, F1 in 2, F2 in 4, F3 in 7 and F4 in 8 patients. FIB-4 failed to correlate with fibrosis stage. The areas under the ROC curves of SSWE, APRI and their combination were 0.79, 0.65 and 0.78 for significant fibrosis, 0.81, 0.64 and 0.76 for advanced fibrosis, 0.82, 0.56 and 0.84 for cirrhosis. SSWE values at biopsy was correlated with platelet count (ru2009=u2009−0.426, Pu2009=u20090.038), serum albumin (ru2009=u2009−0.670, Pu2009<u20090.001), total bilirubin (ru2009=u20090.419, Pu2009=u20090.041) and direct bilirubin levels (ru2009=u20090.518, Pu2009=u20090.010) measured at 6 months after liver biopsy. Our results indicate that SSWE is a more promising tool to assess liver fibrosis than APRI and FIB-4 in children with BA.

Advanced Recurrent Hepatocellular Carcinoma: Treatment with Sorafenib Alone or in Combination with Transarterial Chemoembolization and Radiofrequency Ablation

Purpose To retrospectively investigate the safety and efficacy of sorafenib combined with transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) (hereafter, TACE-RFA) in the treatment of recurrent hepatocellular carcinoma (rHCC) with portal vein tumor thrombosis, extrahepatic metastases (advanced hepatocellular carcinoma), or both after initial hepatectomy. Materials and Methods The study was centrally approved by the ethics committee of three tertiary medical centers in China. From January 2010 to January 2015, 207 consecutive patients with advanced rHCC after initial hepatectomy received sorafenib combined with TACE-RFA (combination group, n = 106) or sorafenib alone (sorafenib group, n = 101) at the three medical centers. Overall survival (OS) and time to progression (TTP) were compared between the two groups. Complications were assessed. Survival curves were constructed with the Kaplan-Meier method and were compared with the log-rank test. Results Baseline characteristics were balanced between the two groups. No treatment-related death occurred in either group. The toxicity profile in the combination group was similar to that in the sorafenib group. After treatment, median OS (14.0 vs 9.0 months, respectively; P < .001) and TTP (7.0 vs 4.0 months, respectively; P < .001) were significantly longer in the combination group than in the sorafenib group. Multivariate analysis showed that treatment allocation was a significant predictor of OS and TTP, while the number of intrahepatic tumors was another prognostic factor of OS. Conclusion Sorafenib combined with TACE-RFA was well tolerated and safe and was superior to sorafenib alone in improving survival outcomes in patients with advanced rHCC after initial hepatectomy.

Combined radiofrequency ablation and ethanol injection versus repeat hepatectomy for elderly patients with recurrent hepatocellular carcinoma after initial hepatic surgery

Abstract Purpose: To retrospectively compare the efficacy and safety of combined radiofrequency ablation and percutaneous ethanol injection (RFA–PEI) with repeat hepatectomy for elderly patients with initial recurrent hepatocellular carcinoma (HCC) after hepatic surgery. Methods: From January 2009 to June 2015, 105 elderly patients (≥70u2009years) who underwent RFA–PEI (nu2009=u200957) or repeated hepatectomy (nu2009=u200948) for recurrent HCCu2009≤u20095.0u2009cm were included in the study. The overall survival (OS) and recurrence-free survival (RFS) were analysed with the Kaplan–Meier method and compared by the log-rank test. Non-tumour-related death, complications and hospital stays were assessed. Univariate and multivariate analyses were performed to identify the prognostic significance of the variables in predicting the OS and RFS. Results: OS rates were 78.2%, 40.8% and 36.7% at 1, 3 and 5u2009years after RFA–PEI and 76.3%, 52.5% and 42.6% after repeat hepatectomy, respectively (pu2009=u20090.413). Correspondingly, the 1-, 3- and 5-year RFS rates after RFA–PEI and repeat hepatectomy were 69.5%, 37.8%, 33.1% and 73.1%, 49.7%, 40.7%, respectively (pu2009=u20090.465). Non-tumour-related deaths in the RFA–PEI group (2/57) were significantly fewer than those in the repeat hepatectomy group (10/48) (pu2009=u20090.016). RFA–PEI was superior to repeat hepatectomy regarding the major complication rates and length of in-hospital stay (both pu2009<u20090.001). Multivariate analysis showed that the tumour number was the significant prognostic factor for the OS (hazard ratio (HR)u2009=u20091.961, 95% CIu2009=u20091.043–3.686, pu2009=u20090.037) and RFS (HRu2009=u20091.866, 95% CIu2009=u20091.064–3.274, pu2009=u20090.030). Conclusion: RFA–PEI provides comparable OS and RFS to repeat hepatectomy for elderly patients with small recurrent HCC after hepatectomy but with fewer non-tumour-related deaths, major complications and shorter hospital stays.

Real-Time Shear Wave Ultrasound Elastography Differentiates Fibrotic from Inflammatory Strictures in Patients with Crohn’s Disease

Background and aimnThe distinction of intestinal fibrosis from inflammation in Crohns disease (CD) associated strictures has important therapeutic implications. Ultrasound elastography is useful in evaluating the degree of fibrosis in liver, but there is little evidence whether it can assess fibrosis in the bowel. We determined whether shear-wave elastography (SWE), a novel modification of elastography, quantifying tissue stiffness, could differentiate between inflammatory and fibrotic components in strictures of patients with CD.nnnMethodsnConsecutive CD patients with ileal/ileocolonic strictures who underwent SWE within 1 week to surgical resection were enrolled. The SWE value of the stenotic bowel wall was compared to the grade and severity of fibrosis and inflammation, respectively, in the resected bowel specimen.nnnResultsnThirty-five patients were enrolled. The mean SWE value of stenotic bowel wall was significantly higher in severe fibrosis (23.0 ± 6.3 Kpa) than that in moderate (17.4 ± 3.8 Kpa) and mild fibrosis (14.4 ± 2.1 Kpa)(P = 0.008). Using 22.55 KPa as the cutoff value in discriminating between mild/moderate and severe fibrosis, the sensitivity and specificity was 69.6 % and 91.7% with an area under the curve (AUC) of 0.822 (P = 0.002). However, no significant difference regarding mean SWE existed among different grades of inflammation. The sensitivity and specificity of bowel vascularization score on conventional ultrasound in differentiating severe inflammation from mild/moderate was 87.5 % and 57.9% with AUC of 0.811 (P = 0.002). Combining SWE and conventional ultrasound (bowel vascularization score), we propose a bowel ultrasound classification of intestinal strictures. A moderate agreement between ultrasound and pathological classification was observed (κ = 0.536, P＜0.001).nnnConclusionsnThis pilot study suggests that SWE is feasible and accurate in detecting intestinal fibrosis in patients with CD. After validation, combing SWE and bowel vascularization on conventional ultrasound might be applied to guide a management strategy in CD patients through defining the type of intestinal stricture. 10.1093/ibd/izy115_video1izy115.video15777734754001.

Stress-induced phosphoprotein 1 mediates hepatocellular carcinoma metastasis after insufficient radiofrequency ablation

Recent studies indicated that insufficient radiofrequency ablation (RFA) could endow hepatocellular carcinoma (HCC) with higher aggressive potential. Stress-induced phosphoprotein 1 (STIP1), which was found highly expressed in HCC, is a chaperone molecule mediating cell homeostasis under thermal stress. We aimed to explore the role of STIP1 on the metastasis of residual HCC after RFA. Mice model with orthotopic HCC implants or caudal vein injection were employed to assess potential of lung metastasis and/or intrahepatic metastasis (IHM) of HCC cells. Cell culture model was used to determine cell invasion, mesenchymal marker genes expression, and underlying molecular mechanisms. Clinical specimens were collected to analyze the relationship between STIP1 and clinical outcome. We found that insufficient RFA elicited more IHM of HCCLM3 tumors, which could be reduced by silencing STIP1. Knockdown of STIP1 also significantly decreased lung metastatic potential of HCCLM3 cells. In vitro, HCCLM3 and HepG2 displayed a spindle-shaped morphology with upregulation of STIP1 and mesenchymal markers after sublethal heat exposure. Mechanistically, heat exposure induced the formation of STIP1-heat shock protein 90 (HSP90) complex, which could shuttle epithelial transcription repressor Snail1 into nucleus and regulate mesenchymal gene transcription. Blocking the HSP90–STIP1 complex reduced the invasive potential of HCC cells after heat exposure. Using clinical specimen, we found that STIP1 was expressed significantly higher in metastatic tumor tissues and in sera from metastatic HCC patients (pu2009<u20090.05). The high expression of STIP1 was significantly linked to shorter recurrence-free survival (pu2009<u20090.05). To sum up, our study found that STIP1 is positively associated with the sublethal heat-induced cancer cell metastasis through mediating the mesenchymal gene transcription. Blocking STIP1 activity may suppress HCC cell metastatic potential after RFA.

Multipronged ethanol ablation combined with TACE for intermediate hepatocellular carcinoma

Abstract Purpose: To retrospectively investigate the efficacy of multipronged ethanol ablation with or without transarterial chemoembolization (TACE) in the treatment of intermediate hepatocellular carcinoma (HCC) (3.1-5.0u2009cm in diameter) at high-risk locations . Material and methods: From March 2009 to April 2014, 25 consecutive patients with intermediate HCC who underwent multipronged ethanol ablation combined with TACE were included in the combination treatment group, while 50 patients who underwent multipronged ethanol ablation alone were included in the control group. Results: Primary technique effectiveness was achieved in 70 patients (25/25, 100% in the combination treatment group; 45/50, 90% in the control group; pu2009=u2009.162). The local tumor progression (LTP) rates at 1, 3, 5, and 7u2009years were 8.0%, 24.0%, 24.0%, and 24.0% in the combination treatment group, respectively, which were significantly lower than those in the control group (24.4%, 44.1%, 66.5% and 66.5%, respectively; pu2009=u2009.043). However, no significant differences of overall survival and disease-free survival were found between the two groups (pu2009=u2009.996 and .974, respectively). Conclusion: Multipronged ethanol ablation combined with TACE could improve local tumor control for patients with intermediate HCC at high-risk locations when compared with multipronged ethanol ablation alone, although the survival outcomes were comparable.

Safety margin after radiofrequency ablation of hepatocellular carcinoma: precise assessment with a three-dimensional reconstruction technique using CT imaging

Abstract Purpose: To analyse the precise ablative margin (AM) after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) and the correlation between AM and local tumour progression (LTP) with a three-dimension (3D) reconstruction technique. Methods: From March 2011 to May 2013, 134 patients who underwent RFA for 159 primary or recurrent HCCs within Milan criteria were enrolled. Contrast-enhanced computed tomography (CECT) scans were performed 1u2009week before and 1u2009month after treatment. The AM was measured in various directions using a 3D reconstruction technique that shows the index tumour and ablated zone on the same image. The average of all obtained AMs (average AM) and the smallest AM (min-AM) were calculated. Results: The min-AM after RFA ranged from 1 to 9.3u2009mm (medianu2009±u2009standard deviation, 4.8u2009±u20091.8u2009mm). LTP was observed in 19 tumours from 19 patients. The median min-AM was 3.1u2009±u20091.6u2009mm for patients with LTP, while the median min-AM of patients without LTP was 5.1u2009±u20091.8u2009mm (pu2009=u20090.023). After RFA, the 1-, 2- and 3-year LTP rates were 10.9, 25.9 and 35.1%, respectively, for patients with min-AM <5u2009mm, and 4.1, 4.1 and 4.1%, respectively, for patients with min-AM ≥5u2009mm (pu2009=u20090.016). Multivariate analysis showed that only min-AM <5u2009mm was an independent risk factor for LTP after RFA (pu2009=u20090.044, hazard ratio =4.587, 95% confidence interval, 1.045–22.296). Conclusions: The 3D reconstruction technique is a precise method for evaluating the post-ablation margin. Patients with min-AM less than 5u2009mm had a higher probability of developing LTP.

Combined transcatheter arterial chemoembolization and radiofrequency ablation versus hepatectomy for recurrent hepatocellular carcinoma after initial surgery: a propensity score matching study

ObjectivesTo compare retrospectively the efficacy of transcatheter arterial chemoembolization (TACE) plus radiofrequency ablation (RFA) (TACE-RFA) with that of repeat hepatectomy in the treatment of initial recurrent hepatocellular carcinoma (HCC) after hepatectomy by propensity score matching (PSM).MethodsFrom September 2006 to June 2015, 186 patients who underwent TACE-RFA (n=107) or repeat hepatectomy (n=79) for recurrent HCC ≤ 5.0 cm were included. The overall survival (OS) and disease-free survival (DFS) were compared. PSM was used to correct potential confounding factors between these two groups.Results1-, 3-, and 5-year OS rates after TACE-RFA and repeat hepatectomy were 84.6%, 66.9%, 49.1%, and 84.8%, 60.2%, 51.9%, respectively (p=.871). The corresponding DFS rates were 58.2%, 35.2%, 29.6% and 64.8%, 41.6%, 38.3% (p=.258). TACE-RFA has lower major complication rates (p=.009) and shorter hospital stay (p<.001). After PSM, 1-, 3-, 5- year OS rates after TACE-RFA (n=51) and repeat hepatectomy (n=51) were 84.3%, 60.4%, 46.4% and 84.3%, 64.5%, 49.8% (p=.951), the corresponding DFS rates were 54.9%, 35.0%, 30.6% and 58.7%, 35.8%, and 33.6% (p=.733). AFP and micro-vessel invasion of initial tumour were significant prognostic factors for OS and DFS, respectively.ConclusionsTACE-RFA provides comparable OS and DFS to repeat hepatectomy, fewer major complications and shorter hospital stay.Key Points• TACE-RFA achieved similar OS and DFS with repeat hepatectomy for recurrent HCC• Major complication rate was lower in the TACE-RFA group• The hospital stay was shorter in the TACE-RFA group• AFP was a predictor for OS, MVI was a predictor for DFS• The treatment strategies were not significant prognostic factor for OS or DFS

Combined percutaneous radiofrequency ablation and ethanol injection versus hepatic resection for 2.1–5.0 cm solitary hepatocellular carcinoma: a retrospective comparative multicentre study

ObjectivesTo compare combined percutaneous radiofrequency ablation and ethanol injection (RFA-PEI) with hepatic resection (HR) in the treatment of resectable solitary hepatocellular carcinoma (HCC) with 2.1–5.0 cm diameter.MethodsFrom June 2009 to December 2015, 271 patients whom underwent RFA-PEI (n = 141) or HR (n = 130) in three centres were enrolled. The overall survival (OS) and recurrence-free survival (RFS) between groups were compared with Kaplan–Meier method and log-rank tests. Complications, hospital stay and cost were assessed.ResultsThe OS rates at 1, 3 and 5 years were 93.5%, 72.7%, 58.6% in RFA-PEI group and 82.3%, 57.5%, 51.8% in HR group (p = 0.021). The corresponding 1-, 3- and 5-year RFS rates were 65.8%, 41.3%, 34.3% in RFA-PEI group and 50.5%, 33.8%, 28.4% in HR group (p = 0.038). For patients with 2.1–3.0 cm tumours, the 1-, 3- and 5-year OS after RFA-PEI and HR were 98.0%, 82.3%, 74.2% and 89.4%, 65.1%, 61.9%, respectively (p = 0.024). The corresponding RFS were 79.6%, 54.7%, 45.1% in RFA-PEI group, and 57.6%, 43.9%, 31.7% in HR group, respectively (p = 0.020). RFA-PEI was superior to HR in major complication rates, length of hospital stay and cost (all p < 0.001).ConclusionRFA-PEI had a survival benefit over HR in the treatment of solitary HCCs, especially for those with 2.1–3.0 cm in diameter.Key Points• RFA-PEI provided superior survival to HR in solitary HCC with 2.1–5.0 cm in diameter.• RFA-PEI is superior to HR in complications, length of hospital stay and cost.• RFA-PEI might be an alternative treatment for solitary HCC within 5.0 cm in diameter.

Sorafenib versus Transarterial chemoembolization for advanced-stage hepatocellular carcinoma: a cost-effectiveness analysis

BackgroundSorafenib and transarterial chemoembolization (TACE) might both provide survival benefit for advanced hepatocellular carcinoma (HCC). Adopting either as a first-line therapy carries major cost and resource implications. We aimed to estimate the cost-effectiveness of sorafenib and TACE in advanced HCC.MethodsA Markov model was constructed in a hypothetical cohort of patients aged 60xa0years with advanced HCC and Child-Pugh A/B cirrhosis over a 2-year time frame. Three strategies (full or dose-adjusted sorafenib and TACE) were compared in two cost settings: China and the USA. Transition probabilities, utility and costs were extracted from systematic review of 27 articles. Sensitivity analysis and Monte Carlo analysis were conducted.ResultsFull and dose-adjusted sorafenib respectively produced 0.435 and 0.482 quality-adjusted life years (QALYs) while TACE produced 0.375 QALYs. The incremental cost-effectiveness ratio (ICER) of full-dose sorafenib versus TACE was