Hepatocellular Carcinoma Nodules Research Articles

The Role of Endoglin in Hepatocellular Carcinoma.

Endoglin (CD105) is a type-1 integral transmembrane glycoprotein and coreceptor for transforming growth factor-β (TGF-β) ligands. The endoglin/TGF-β signaling pathway regulates hemostasis, cell proliferation/migration, extracellular matrix (ECM) synthesis and angiogenesis. Angiogenesis contributes to early progression, invasion, postoperative recurrence, and metastasis in hepatocellular carcinoma (HCC), one of the most widespread malignancies globally. Endoglin is overexpressed in newly formed HCC microvessels. It increases microvessel density in cirrhotic and regenerative HCC nodules. In addition, circulating endoglin is present in HCC patients, suggesting potential for use as a diagnostic or prognostic factor. HCC angiogenesis is dynamic and endoglin expression varies by stage. TRC105 (carotuximab) is an antibody against endoglin, and three of its clinical trials were related to liver diseases. A partial response was achieved when combining TRC105 with sorafenib. Although antiangiogenic therapy still carries some risks, combination therapy with endoglin inhibitors or other targeted therapies holds promise.

NCP:Fe Nanocontrast Agent for Magnetic Resonance Imaging-Based Early Detection of Liver Cirrhosis and Hepatocellular Carcinoma.

Early detection of liver tumors and cirrhotic lesions by magnetic resonance imaging (MRI) remains a great challenge. Here, we report a biomineral nanocontrast agent based on iron-doped nanocalcium phosphate (nCP:Fe-CA) for magnetic resonance imaging of early-stage liver cirrhotic and hepatocellular carcinoma nodules using rat models. We have optimized an intravenously injectable, aqueous suspension of nCP:Fe-CA having an average size of 137.6 nm, a spherical shape, magnetic relaxivity of 63 mM-1S-1, and colloidal stability for 48 h, post-resuspension in an aqueous phase. Compared to superparamagnetic iron oxide nanoparticles (SPIONs), the optimized nCP:Fe-CA could detect liver tumor lesions as small as ∼0.25 cm, whereas the current clinical detection limit is ∼1 cm. In addition, multiple cirrhotic nodules of size <0.2 cm could be detected by nCP:Fe-CA-assisted MRI. The number of nodules observed after injecting nCP:Fe-CA was ∼3 times higher than that without CA (5-10 nodules). A biocompatibility study on healthy rats injected with nCP:Fe-CA showed unaltered liver transaminases, blood urea nitrogen, serum creatinine, and insignificant hemolysis. Furthermore, hepatobiliary clearance of nCP:Fe-CA was observed in 72 h compared to prolonged retention of SPIONs for 30 days when tested under identical conditions. Overall, the nCP:Fe-CA nanoparticles showed promising results as a biocompatible, MR contrast (T2) agent for the early-stage imaging of liver cirrhosis and hepatocellular carcinoma.

Number of hepatocellular carcinoma nodules in patients listed for liver transplantation within alpha-fetoprotein score: a new prognostic risk factor.

In France, the listing for liver transplantation (LT) for hepatocellular carcinoma (HCC) requires an AFP score ≤2. This study evaluates whether the number of nodules assessed immediately before LT has a prognostic value among patients already listed within AFP score. Among 143 recipients transplanted with an AFP score ≤2 between 2013 and 2017 in our center, the number of nodules was considered at listing on the waiting list and at last imaging before LT. We compared the overall survival (OS) and disease-free survival (DFS) post-LT of patients with ≤3 and >3 nodules (current classification), and aimed to propose a new criteria to exclude patients on list at high risk of recurrence. The 3-year OS of patients with ≤3 HCC vs. >3 HCC at listing was of 90.3% vs. 67.3%, respectively (P=0.04). At last imaging, eight listed patients presented ≥5 HCC nodules and had a significantly lower OS than <5 nodules patients (5-year OS: 24.4% vs. 78.1%; P=0.01). Although the current AFP score offers satisfactory outcomes, we highlight the poorer outcomes when ≥5 nodules persist or appear after listing. A modification of the AFP score is mandatory to consider exclusion of high-risk patients already listed for LT program.

Improving Ablation Safety for Hepatocellular Carcinoma Proximal to the Hilar Bile Ducts by Ultrasound-MR Fusion Imaging: A Preliminary Comparative Study.

AimTo explore whether ablation safety could be improved by ultrasound (US)-magnetic resonance (MR) fusion imaging for hepatocellular carcinoma (HCC) proximal to the hilar bile ducts (HBDs) through a preliminary comparative study.MethodsBetween January 2014 and June 2019, 18 HCC nodules proximal to the HBDs were included in a US-MR fusion imaging-assisted radiofrequency ablation (RFA) group (study group), while 13 HCC nodules in a similar location were included as a control group. For the study group, the tumor and adjacent bile ducts were outlined on preprocedural MR images. Procedural ablation planning was conducted to assess the feasibility of ablating the tumors while avoiding biliary injury. Such tumors were then ablated under US-MR fusion imaging guidance. The control group nodules were ablated under conventional ultrasound guidance. Baseline characteristics and outcomes were compared between the groups.ResultsAfter preprocedural assessment, 14 of 18 patients with tumors that were feasible to ablate underwent US-MR fusion imaging-assisted RFA. No biliary complications were observed in these 14 patients; the complication rate was significantly lower in the study group than in the control group (30.8%, 4/13) (P = 0.041). There was no significant difference in the technique efficacy rates [92.9% (13/14) versus 100% (13/13), P = 1] or local progression rates [7.1% (1/14) versus 7.7% (1/13), P = 1] between the study and control groups.ConclusionsUS-MR fusion imaging may be a non-invasive means for assisting RFA of HCC nodules proximal to the HBDs and ensuring ablation safety.

High Expression of LINC01268 is Positively Associated with Hepatocellular Carcinoma Progression via Regulating MAP3K7.

ObjectiveAs one of the most common neoplastic diseases, hepatocellular carcinoma (HCC) has a high morbidity and mortality, which seriously threatens human health and places a heavy burden on society and medical care. At present, effective early diagnosis, prognosis and treatment of HCC are limited. Altered gene expression patterns of lncRNA are associated with the occurrence, development and prognosis of various malignancies, including HCC. The aim of this study was to investigate the correlation between the expression of LINC01268 and HCC, and to elucidate the potential underlying molecular mechanism.MethodsExpression level and localization of LINC01268 in human liver cancer cells and HCC tissues were investigated using RT-qPCR and fluorescent in situ hybridization (FISH), respectively. Correlation of expression levels of LINC01268 and MAP3K7 with differentiation and poor overall patient survival of HCC were analyzed using in house collected and publicly available HCC tissue data. RT-qPCR and Western blot were applied to inspect the effects of depletion and overexpression of LINC01268 on MAP3K7 expression. HCC cell proliferation and apoptosis were also investigated by simultaneous overexpression of LINC01268 and knockdown of MAP3K7, in order to delineate that MAP3K7 is a downstream effector of LINC01268.ResultsIn this study, we identified that LINC01268 was highly expressed in HCC cell lines and tissues. High LINC01268 expression level was associated with lower HCC nodule number, moderate/poor differentiation and poor overall survival. Knockdown of LINC01268 inhibited the proliferation of HCC cells, which was enhanced by overexpression of LINC01268. Co-expression analysis implied an interaction between LINC01268 and MAP3K7. Similar to LINC01268, MAP3K7 was highly expressed in HCC cells, and positively correlated with moderate/poor differentiation as well as poor prognosis. Knockdown of LINC01268 in HCC cell lines led to reduction of MAP3K7 at both mRNA and protein levels. Phenotypic effects due to LINC01268 overexpression in HCC cells were reversed by knockdown of MAP3K7.ConclusionTaken together, the abnormal high expression of LINC01268 is associated with HCC progression via regulating MAP3K7, suggesting LINC01268 as a novel marker for HCC prognosis and potentially a new therapeutic target.

Higher Efficiency of Percutaneous Microwave (MWA) Than Radiofrequency Ablation (RFA) in Achieving Complete Response in Cirrhotic Patients with Early Hepatocellular Carcinoma.

Background: Contrasting data are available in the literature regarding the superiority of percutaneous microwave ablation (MWA) or radiofrequency ablation (RFA) in very early or early (BCLA 0 or A) hepatocellular carcinoma (HCC). Aims: The primary outcome was to compare the efficacy of RFA and MWA in achieving complete response in cirrhotic patients with early and very early HCC. The secondary outcomes were to evaluate the overall survival and the recurrence rate. Methods: A retrospective, observational, single-center study was performed. Inclusion criteria were liver cirrhosis, new diagnosis of a single node of HCC measuring a maximum of 50 mm or up to three nodules with diameter up to 35 mm, treatment with RFA or MWA. Radiological response was evaluated with multiphasic contrast-enhanced Computed Tomography or Magnetic Resonance Imaging at 5–7 weeks after thermal ablation. Complete response was defined when no vital tissue was detected after treatment. Results: Overall, 251 HCC patients were included in this study; 81 patients were treated with MWA and 170 with RFA. The complete response rate was similar in MWA and RFA groups (out of 331 nodules, 87.5% (91/104) were treated with MWA and 84.2% (186/221) were treated with RFA, p = 0.504). Interestingly, a subanalysis demonstrated that for 21–35 mm nodules, the probability to achieve a complete response using MWA was almost 5 times higher than for RFA (OR = 4.88, 95% CI 1.37–17.31, p = 0.014). Moreover, recurrence rate in 21–35 mm nodules was higher with RFA with respect to MWA (31.9% versus 13.5%, p = 0.019). Overall survival was 80.4% (45/56) when treated with MWA and 62.2% (56/90) when treated with RFA (p = 0.027). No significant difference was observed between MWA and RFA treatment in the 15–20 mm nodules group. Conclusion: This study showed that MWA is more efficient than RFA in achieving complete response in HCC nodules with 21 to 35 mm diameter.

Morus nigra L. extract prolongs survival of rats with hepatocellular carcinoma.

Morus nigra is a rich source of anthocyanins, phytochemicals that have anticancer effects. This study aimed to investigate the effects of M. nigra extract (MNE) on diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC). Male Sprague-Dawley rats were assigned into four groups (n=10): control, DEN, and DEN +100 or 400 mg/kg of MNE. After 4 months, the DEN group showed a significant mortality rate, hepatic lipid peroxidation, dysplastic nodules in the cirrhotic liver, and an increase of blood bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). Also, the body weight gain, blood albumin and glucose, liver antioxidant capacity (thiol groups), and some hematological parameters (RBC, hematocrit, hemoglobin, and platelet) were significantly decreased in the DEN group. MNE significantly increased survival, reduced the size of HCC nodules, improved liver oxidant/antioxidant status, and prevented the above-mentioned changes in the blood (except ALP, glucose, and platelet). Quantitative real-time PCR showed that MNE decreased the expression of Wnt4 and β-catenin, while had no significant effect on PI3K, Akt, and PTEN expression. The MNE did not exhibit antiproliferative activity against HepG2 liver cancer cells. In conclusion, MNE exhibits a hepatoprotective effect through inhibiting oxidative stress and Wnt4/β-catenin pathway and therefore prolongs the survival of rats with HCC.

Usefulness of virtual parenchymal perfusion software visualizing embolized areas to determine optimal catheter position in superselective conventional transarterial chemoembolization for hepatocellular carcinoma.

To determine the optimal catheter position during superselective conventional transarterial chemoembolization (cTACE) for hepatocellular carcinoma (HCC) using virtual parenchymal perfusion software. Patients who had newly developed HCC nodules ≤6cm and five or fewer lesions were eligible. The virtual catheter tip was placed on a tumor-feeder identified by TACE guidance software using cone-beam computed tomography during hepatic arteriography to minimize the virtual embolized area (VEA), including the tumor with a safety margin. Conventional transarterial chemoembolization was then carried out at the same position. The VEA and real embolized area where iodized oil was retained on cone-beam computed tomography after cTACE were compared using the dice similarity coefficient, linear regression analysis, and mean surface distance. Technical success of cTACE and therapeutic effects by the modified Response Evaluation Criteria in Solid Tumors were also evaluated. Ninety-one tumors in 56 patients were embolized. The mean dice similarity coefficient values in 80 VEAs and real embolized areas were 0.78±0.01. Both volumes were well correlated (r=0.957, p<0.001) with a mean surface distance of 2.78±2.11mm. Eighty-four (92.3%) tumors were embolized with a safety margin. Regarding the early response of 82 tumors, complete response was achieved in 72 (87.8%), partial response in six (7.3%), and stable disease in four (4.9%). Regarding responses of 81 tumors during the follow-up (mean, 20±4.9months), complete response was maintained in 62 (76.5%), whereas 19 (23.5%), including six that were incompletely embolized, locally progressed. Virtual parenchymal perfusion software can determine the optimal catheter position in superselective cTACE.

OATP1B3 Expression in Hepatocellular Carcinoma Correlates with Intralesional Gd-EOB-DTPA Uptake and Signal Intensity on Gd-EOB-DTPA-Enhanced MRI.

BackgroundTo evaluate the predictive value of the OATP1B3 expression in hepatocellular carcinoma (HCC) for the gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) uptake and the signal intensity (SI) in the hepatobiliary (HB) phase.MethodsIn this retrospective study, we analyzed 69 liver nodules of 64 patients who underwent Gd-EOB-DTPA enhancement magnetic resonance imaging (MRI) before operation. Based on the SI in the HB phase, the patients were categorized into the hypointense HCC and iso- or hyperintense HCC groups. The OATP1B3 expression was detected by polymerase chain reaction (PCR) and immunohistochemistry. The differences between the expression of OATP1B3 and Gd-EOB-DTPA enhanced magnetic resonance imaging between the two groups of hepatocellular carcinoma were compared. The relationship between the OATP1B3 expression and the SI and relative enhancement (RE) was analyzed.ResultsThe examined HCC nodules were 59 hypointense HCC and 10 iso- or hyperintense. The relative expressions of OATP1B3, HB-phase signal, and the RE of the HB phase in iso- or hyperintense were significantly higher than those of the hypointense HCC, while the RE of the HB phase increased with an increase in the OATP1B3 expression (P < 0.05).ConclusionThe OATP1B3 expression in HCC can predict the uptake of Gd-EOB-DTPA and the SI of the HB phase. We believe that the evaluation of OATP1B3 expression will facilitate the comprehension of imaging performance of HCC in Gd-EOB-DTPA-enhanced MRI.

Comparative Analysis of Radiofrequency Ablation and Microwave Ablation for Critically Located Hepatocellular Carcinomas Smaller than 5 cm

AbstractPurpose To compare the safety and efficacy of radiofrequency ablation (RFA) versus microwave ablation (MWA) for hepatocellular carcinomas (HCC) smaller than 5 cm in critical locations.Methods Single-center retrospective study of all patients who underwent RFA/MWA for HCC from July 2015 to Dec 2019. Critical location includes exophytic tumors, tumors ≤ 5 mm from the diaphragm, heart, gallbladder, kidney, gastrointestinal tract, and ≤ 10 mm from large vessels with caliber of ≥ 3 mm. Treatment effectiveness, local tumor progression, and complication rates were evaluated.Results Out of 119 patients with 147 HCC nodules in critical location, 65 (M:F = 49:16; mean age–61.7) were included in RFA group and 54 (M:F =43:11; mean age–60.5) in MWA group. Mean follow-up period was 16.5 and 14.8 months, respectively. At first follow-up imaging, 66/78 tumors in RFA group and 57/69 tumors in MWA group showed complete ablation with primary treatment effectiveness rates of 84.6% and 82.6%, respectively (p = 0.741). Local tumor progression (LTP) rate was 21.8% (17/78) and 20.3% (14/69), respectively (p = 0.826). Median time to LTP was 12 and 13.5 months, respectively. Fourteen tumors in RFA group and 12 in MWA group underwent reablation with a secondary treatment effectiveness rates of 78.6% (14/17) and 83.3% (12/14), respectively (p = 0.757). Mean LTP-free survival was 37.2 and 28.1 months, respectively. The total complication rate was 36.9% and 31.5%, respectively (p = 0.535) with no major complications in both the groups.Conclusion Our data suggest that both MWA and RFA are equally safe and effective for treating HCCs &lt; 5 cm in critical locations.

Higher Enhancement Intrahepatic Nodules on the Hepatobiliary Phase of Gd-EOB-DTPA-Enhanced MRI as a Poor Responsive Marker of Anti-PD-1/PD-L1 Monotherapy for Unresectable Hepatocellular Carcinoma

Introduction: Immune checkpoint inhibitors (ICIs) are promising agents for the treatment of hepatocellular carcinoma (HCC). However, the establishment of noninvasive measure that could predict the response to ICIs is challenging. This study aimed to evaluate tumor responses to ICIs using the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI), which was shown to reflect Wnt/β-catenin activating mutation. Methods: A total of 68 intrahepatic HCC nodules from 18 patients with unresectable HCC and Child-Pugh class A liver function who received anti-programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1) monotherapy were enrolled in this study. All patients had viable intrahepatic lesions evaluable using the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI within the 6 months prior to the treatment. The relative enhancement ratio was calculated, and the time to nodular progression (TTnP) defined as 20% or more increase in each nodule was compared between higher or hypo-enhancement HCC nodules. Then, the progression-free survival (PFS) and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) were compared between patients with and without HCC nodules with higher enhancement on hepatobiliary phase images. Results: The median PFS was 2.7 (95% confidence interval [CI]: 1.4–4.0) months in patients with HCC nodules with higher enhancement (n = 8) and 5.8 (95% CI: 0.0–18.9) months in patients with hypointense HCC nodules (n = 10) (p = 0.007). The median TTnP of HCC nodules with higher enhancement (n = 23) was 1.97 (95% CI: 1.86–2.07) months and that of hypointense HCC nodules (n = 45) was not reached (p = 0.003). The ORR was 12.5% (1/8) versus 30.0% (3/10); the disease control rate was 37.5% (3/8) versus 70.0% (7/10), respectively, in patients with or without higher enhancement intrahepatic HCC nodules. Conclusion: The TTnP on HCC nodules with higher enhancement and the median PFS in patients who carried higher enhancement intrahepatic HCC nodules were significantly shorter than those in hypointense HCC nodules with anti-PD-1/PD-L1 monotherapy. The intensity of the nodule on the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI is a promising imaging biomarker for predicting unfavorable response with anti-PD-1/PD-L1 monotherapy in patients with HCC.

COVID-19 Mid-term Impact on Hepatocellular Carcinoma in Patients With Hepatitis C Chronic Infection.

Liver injury has been frequently reported in association with SARS-CoV-2 infection, but data are still lacking regarding the impact of pre-existing liver damage and neoplasia on SARS-CoV-2 infection outcome and vice-versa. This study aimed to assess the effects of SARS-CoV-2 infection on hepatocellular carcinoma (HCC) in chronic hepatitis C virus (HCV) infected patients, both in therapeutic-naïve and patients treated with direct acting antivirals. We conducted a retrospective cohort study on 21 patients with a personal history of HCV infection, that have been diagnosed with different forms of HCC and who were subsequently infected with SARS-CoV-2. Patients were monitored by liver function tests, tumoral markers, blood cell count, and coagulation profile periodically. Solitary HCC nodules were predominant among the subjects who achieved sustained virologic response, while multinodular and infiltrative patterns were mostly prevalent among the treatment-naïve group. Most patients had mild and moderate COVID-19 infections. Within the current global pandemic crisis, cancer patients are highly vulnerable and in need of constant monitoring. Among patients with HCC, the ones with cured HCV infection may be at a lower risk of fatality than those with active HCV infection, when diagnosed with SARS-CoV-2 infection.

Difficult HCC of segment 1 in retrocaval position laparoscopic liver resection using ICG and CEIOUS

Background: Contrast-enhanced intraoperative ultrasonography (CEIOUS) is a well known technique used in liver surgery to improve identification and resection of hepatocellular carcinoma ( HCC ) nodules. In recent years , the use of indocyanine green (ICG ) fluorescence has grown in hepatobiliary surgery 1,2 . The range of applications of ICG is various, from the ability to identify biliary anatomy during cholecystectomy to the visualization of HCC nodules based on the accumulation of ICG in cancerous tissues. The combinations of the two technologies could increase tumor detection and the radicality of resection. In this video we present a case of ICG- and CEIOUS-guided laparoscopic liver resection of HCC located in segment 1. Materials and Methods: We present the case of a 81-year-old patient with a history of hypertension and treated hepatitis C infection with a sustained serological response from 2018 and a previous laparotomic resection for a HCC in segment 8. During his regular hepatological follow-up a 25 mm nodule is segment 1 was detected in a retrocaval position. Considering clinical presentation, good liver function (Child A5 - MELD 8 ) and imaging, the patient was scheduled for laparoscopic liver resection. Results and Conclusions: We performed a ICG and CEIOUS guided LLR of segment 1. Surgical specimen margins were free from disease and the patient was discharged in postoperative day 4. CEIOUS and ICG can be combined to help the surgeon to detect the exact position of a deep nodule, covered by the caval vein, allowing better oncological results. Further studies are needed to assess the real benefits of the synchronous application of those technologies.

Feasibility and Techniques of Securing 3D-Safety Margin in Superselective Transarterial Chemoembolization to Improve Local Tumor Control for Small Hepatocellular Carcinoma: An Intend-to-Treat Analysis

Introduction: The aim of this study was to investigate the technical success rate of obtaining 3D-safety margin in superselective conventional transarterial chemoembolization (cTACE) using 3D images for small hepatocellular carcinoma (HCC). Methods: Consecutive 48 HCC nodules (diameter, 1–3 cm) in 44 patients were intentionally treated by superselective cTACE in an attempt to achieve 3D-safety margin. Superselective CT during hepatic arteriography (CTHA) was obtained before cTACE. When negative 3D-safety margin was found, branches supplied into the margin area were detected by using a 3D workstation. The technical success rate to obtain 3D-safety margin was investigated by intend-to-treat analysis. Local tumor recurrence rate and adverse events were also evaluated. Result: Nine of 48 tumors (18.8%) had 3D-safety margin in the initial superselective CTHA. After pulling back of the catheter and/or selection of another branch based on 3D images, 3D-safety margin was finally achieved in 45 (93.8%). There were 8 of 46 tumors (17.4%) with local recurrence after 5-year follow-up. Grade 3–4 of aspartate aminotransferase, alanine aminotransferase, and total bilirubin were found in 38.6, 36.4, and 2.3%, respectively. One portal vein thrombus and 3 biliary dilation or biloma were developed. Conclusion: Superselective cTACE obtaining 3D-safety margin in small HCC was feasible with a high success rate by using 3D images, which could be tolerable and prevent local tumor recurrence.

Study on clinical application of susceptibility weighted imaging ombined with diffusion weighted imaging in patients with Liver Cirrhosis complicated with small Hepatocellular Carcinoma.

Objectives:To evaluate the clinical value of susceptibility weighted imaging (SWI) combined with diffusion weighted imaging (DWI) in patients with liver cirrhosis complicated with small hepatocellular carcinoma (SHCC).Methods:A total of 40 patients with liver cirrhosis and 44 nodules were treated with conventional nuclear magnetic scanning (T1WI, T2WI) and SWI combined with DWI; the results were judged by two senior physicians; the t test, χ2 test, rank sum test, and other methods were used for contrastive analysis of the pathological results of different scanning methods after operation or puncture.Results:Contrast analysis of the different MRI scanning methods and pathological results showed that among the 32 nodules of small hepatocellular carcinoma, 24 cases were diagnosed by conventional MRI, with the coincidence rate being 75%, 30 cases were diagnosed by SWI DWI, with the coincidence rate being 96%; significant difference was found between the two groups (p=0. 04). Significant differences were found in the specificity, sensitivity and accuracy of different scanning methods in the diagnosis of small hepatocellular carcinoma (specificity, accuracy, p=0.04; sensitivity p=0.01). The SWI of small hepatocellular carcinoma nodules showed hyperintensity, and the degree of iron deposition was low. Significant difference was found between small hepatocellular carcinoma nodules and other nodules (comparison of SWI signal degree, p=0.01; comparison of iron deposition degree, p=0.00).Conclusion:The SWI of small hepatocellular carcinoma nodules showed hyperintensity, and the degree of iron deposition was low. The coincidence rate of SWI+DWI scanning is higher than that of conventional scanning methods in the diagnosis of small hepatocellular carcinoma, and the difference in specificity, sensitivity and accuracy has obvious advantages. SWI+DWI scanning can improve the detection rate of liver cirrhosis complicated with small hepatocellular carcinoma.

Augmented Reality and the Novel Use of Indocyanine Green as a Navigational Adjunct for Laparoscopic Ablation of Liver Tumors

Introduction: Laparoscopy can be used as an adjunct to successfully treat hepatocellular carcinoma nodules, as the surgeon manipulates the liver under direct visualization. To successfully perform laparoscopic assisted thermal ablation the surgeon must be skilled at ultrasound to identify the tumor nodule(s). In this study we introduce a novel adjunct to laparoscopic assisted microwave ablation via IV infusion of indocyanine green (ICG) dye.

Small Steatotic HCC: A Radiological Variant Associated With Improved Outcome After Ablation.

Percutaneous thermal ablation is a validated treatment option for small hepatocellular carcinoma (HCC). Steatotic HCC can be reliably detected by magnetic resonance imaging. To determine the clinical relevance of this radiological variant, we included 235 patients (cirrhosis in 92.3%, classified Child‐Pugh A in 97%) from a prospective database on percutaneous thermal ablation for <3 cm HCC. Among these patients, 52 (22.1%) had at least one steatotic HCC nodule. Nonalcoholic steatohepatitis was more frequent in patients with than without steatotic HCC (P = 0.057), whereas body mass index, diabetes mellitus, liver steatosis, and liver fat content did not differ between groups. Liver disease was less advanced in patients with than without steatotic HCC: lower total bilirubin (‐2.1 µmol/L; P = 0.035), higher albumin (+0.8 g/L; P = 0.035), and lower Model for End‐Stage Liver Disease score (‐0.8; P = 0.014). Tumor phenotype was less aggressive in patients with steatotic HCC: lower alpha‐fetoprotein (AFP) concentration (P = 0.019), less frequent AFP > 100 ng/mL (P = 0.045), and multifocality (P = 0.015). During the follow‐up (median: 28.3 months), overall mortality (3.8% vs. 23.5%; P = 0.001) and HCC‐specific mortality (0.0% vs. 14.2%; P = 0.002) rates were lower in patients with steatotic HCC. Early (<2 years) recurrence was also less frequent (32.7% vs. 49.2%; P = 0.041). The mean time to intrahepatic distant recurrence (16.4 vs. 9 months, P = 0.006) and the median time to recurrence and recurrence‐free survival (32.4 vs. 18.6 months, P = 0.024 and 30.4 vs. 16.4 months, P = 0.018) were longer in patients with steatotic versus nonsteatotic HCC. The 3‐year overall survival was 94.4% and 70.9% in steatotic and nonsteatotic HCC (P = 0.008). In multivariate analysis, steatotic HCC (hazard ratio = 0.12; P = 0.039) and AFP (HR=1.002; P < 0.001) independently predicted overall survival. Conclusion: Small steatotic HCC detected by magnetic resonance imaging is associated with a less aggressive tumor phenotype. In patients with such radiological variant, percutaneous thermal ablation results in improved outcome.

Sinusoidal Endothelial Cell Progenitor Cells Promote Tumour Progression in Patients with Hepatocellular Carcinoma.

Objective As sinusoidal endothelial cell progenitor cells (SEPCs) play a significant role in liver regeneration, it is necessary to elucidate whether SEPCs participate in tumour progression of hepatocellular carcinoma (HCC). Methods A total of 45 patients with primary HCC who underwent liver resection were included in this study. The liver tumours were removed from the patients, and partial tissues were prepared to identify SEPCs through double staining of CD133/CD45 and CD133/CD31 at the same location. Blood samples were collected to examine liver function parameters and tumour markers. The demographics and clinicopathological characteristics of the patients were collected for correlation analysis with SEPCs. Results SEPCs were observed in several blood vessels within the HCC nodules of all 45 patients, but no SEPCs were detected in the tumour-adjacent tissues. The number of SEPCs was correlated with the expression levels of HCC tumour markers α-fetoprotein (AFP) and CA199. There was a positive correlation between the expression of SEPC markers and diameter of HCC tumours in differently differentiated specimens (P < 0.01). The expression levels of SEPC markers were significantly higher in patients with poorly differentiated HCC than in patients with moderately and highly differentiated HCC (P < 0.05). Conclusions SEPCs are closely associated with HCC progression; therefore, SEPCs may be considered potential prognostic and metastatic biomarkers and therapeutic candidates for HCC.

Preablation three-dimensional ultrasonography can predict therapeutic effect and local tumor progression after radiofrequency ablation for hepatocellular carcinoma

PurposeTo assess the agreement between ablative margin (AM) predicted by preablation three-dimensional ultrasonography (3D-US) and AM measured on postablation computed tomography (CT)/magnetic resonance (MR) images. MethodsSixty patients with 73 hepatocellular carcinoma nodules were enrolled. 3D-US data were collected immediately after puncture by the electrode before ablation. The maximum distance from the electrode to the edge of the tumor in the plane perpendicular to the electrode (C-plane) was defined as “a” and the diameter of the ablation zone as “b”. We classified predicted AM into “0.5b − a” ≥0 mm as AM(+) or <0 mm as AM(−), and “0.5b − a” ≥3 mm or <3 mm. ResultsForty-eight nodules (66 %) were visualized in the C-plane. There was an agreement between the predicted and measured AMs for 39 (81 %) of the 48 nodules. Local tumor progression was observed in 3 (7%) of 43 nodules with predicted AM(+) and in 2 (40 %) of 5 nodules with predicted AM(−) but was not observed in any of 21 nodules with predicted AM ≥ 3 mm. The local tumor progression rate was significantly lower for nodules with predicted AM(+) compared with predicted AM(−)(p = 0.03), and for nodules with predicted AM ≥ 3 mm compared with predicted AM < 3 mm (p = 0.04). Local progression was detected in 2 (4.7 %) of 42 nodules with a sufficient AM (≥0 mm) on postablation CT/MR images and in 5 (83.3 %) of 6 nodules with an insufficient AM (<0 mm); the difference in progression rate was significant (p = 0.0008). Conclusion3D-US allows prediction of the AM before radiofrequency ablation.

Enhanced patterns on intraoperative contrast-enhanced ultrasonography predict outcomes after curative liver resection in patients with hepatocellular carcinoma.

This study aimed to clarify what hepatocellular carcinoma (HCC) phenotype, as categorized by intraoperative contrast-enhanced ultrasonography (CEUS), showed a high risk of recurrence after hepatic resection. Patients who underwent initial curative hepatectomy with intraoperative CEUS for a single HCC nodule were retrospectively assigned to three patterns of fine (FI), vascular (VA), and irregular (IR) according to the maximum intensity projection pattern based on intraoperative CEUS. Staining was performed for Ki-67, pyruvate kinase type M2 (PKM2), and vascular endothelial growth factor (VEGF) to assess the tumor proliferative activity, tumor glucose metabolism, and angiogenesis, respectively. Of 116 patients, 18, 50, and 48 were assigned to the FI, VA and IR patterns, respectively. IR patients demonstrated a significantly worse prognosis for both the recurrence-free survival (RFS) and overall survival (OS) (P = 0.0002, 0.0262, respectively) than did patients with other patterns. A multivariate analysis revealed an IR pattern in intraoperative CEUS to be an independent predictive factor for a poor RFS, and major hepatectomy and an IR pattern were independent predictive factors for a poor OS. An IR pattern was closely related to the tumor size (≥ 3.3cm) and poor histological differentiation and showed a high Ki-67 index, low VEGF expression, and high PKM2 expression. IR-pattern HCCs as classified by intraoperative CEUS may be associated with a higher risk of recurrence and worse outcomes in HCC patients after hepatic resection than other patterns.