Small Hepatocellular Carcinoma Research Articles

Prognosis and Risk Factors of Recurrence in HBV-Related Small Hepatocellular Carcinoma After Stereotactic Body Radiation Therapy.

ObjectiveThe role of stereotactic body radiation therapy (SBRT) for treating small hepatocellular carcinoma (sHCC) has gained increasing recognition. However, the prognosis and risk factors for recurrence in patients with sHCC remain unclear. This study investigated the risk factors for the recurrence of hepatitis B virus (HBV)-related sHCC after SBRT.MethodsA total of 240 HBV-related sHCC patients treated with SBRT between March 2011 and March 2020 were retrospectively analyzed. The cumulative probability of recurrence was calculated according to the Kaplan–Meier method. Univariate and multivariate analyses were performed with Cox proportional hazard models.ResultsRecurrent hepatocellular carcinoma developed in 134 (55.8%) patients at a median time of 27 months after SBRT. The one- and two-year rates of recurrence were 20.9 and 45.0%, respectively. The median follow-up time was 30 months. The Cox multivariate analysis indicated that age (P = 0.029, HR [1.019, 1.002–1.037]), tumor size (P = 0.012, HR [1.227, 1.045–1.440]), and aspartate aminotransferase-to-platelet ratio index (APRI) (P = 0.005, HR [1.911, 1.221–2.989]) were independent risk factors for recurrence.ConclusionPatients receiving SBRT for HBV-related sHCC may be at greater risk of recurrence if they have a high APRI score combined with advanced age and large tumor size.

Two-Phase MDCT Protocol for the Screening of Small Hepatocellular Carcinoma.

Screening programmes for cirrhotic patients are based on ultrasound (US) examinations at 6-month intervals, but a US sensitivity of 47% has recently been reported. The aim of this study was to evaluate a two-phase MDCT protocol in terms of hepatic nodule detection within a hepatocellular carcinoma (HCC) screening situation and to evaluate a reduction in irradiation dose for the 6-monthly checks compared to the classic four-phase protocol. In total, 373 patients with 498 nodules that were suspected to be HCC and ranged from 10 to 30 mm in size were prospectively included. All patients underwent four-phase MDCT with an unenhanced phase, arterial phase (AP), portal phase (PP) and delayed phase (DP). The cumulative irradiation from the repeated 6-monthly MDCT protocol was calculated. Of the 498 nodules, only 4 (0.008%) were only seen in the PP and not in the AP or AP. Of the 319 HCC nodules, 270 (84.6%) had AP hyperenhancement, while 115 had washout in the PP and 224 had washout in the DP. Overall, 222 of the 224 (99.1%) HCC nodules with typical features were seen in the AP and DP. The dose reduction was estimated at 55.4% when using the two-phase protocol (AP and DP). The cumulative irradiation of the two-phase protocol, which was performed every 6 months over 5 years, was 96.5 mSv. MDCT with the two-phase protocol could offer an alternative to ultrasound screening with an interesting risk–benefit trade-off.

Safety and efficacy of pentazocine-midazolam combination for pain and anxiety relief in radiofrequency ablation therapy for hepatocellular carcinoma.

Background and AimRadiofrequency ablation (RFA) therapy is frequently used as first‐line treatment for small hepatocellular carcinoma (HCC). RFA is often associated with pain; however, no definitive solution has been established for its relief. We retrospectively analyzed the safety and efficacy of the combination of pentazocine and midazolam to relieve pain experienced by HCC patients undergoing RFA.MethodsWe studied 77 patients with 98 HCCs treated with RFA between January 2015 and August 2019. Patients were divided into two groups: the sedative‐free group, which included those who received pentazocine alone, and the pentazocine–midazolam group, which included those who received a combination of pentazocine and midazolam. The degrees of analgesia and sedation were evaluated using the numerical rating scale (NRS) and the Richmond Agitation‐Sedation Scale (RASS), respectively. Other parameters such as treatment time, awakening time, midazolam dosage, vital signs, local recurrence rate, and time to recurrence were also examined.ResultsThe median NRS score and RASS score were significantly lower in the pentazocine–midazolam group. Ninety‐five percent of patients in the pentazocine–midazolam group had no memory of the RFA session. The treatment time and awakening time were prolonged for the pentazocine–midazolam group. No significant differences in oxygen saturation, recurrence rates, and time to local recurrence were observed between groups.ConclusionA combination of pentazocine and midazolam is safe and effective for pain and anxiety relief experienced by patients undergoing RFA for local treatment of HCC.

State-of-the-art review on the correlations between pathological and magnetic resonance features of cirrhotic nodules.

Hepatocellular carcinoma (HCC) has become the second greatest cause of cancer-related mortality worldwide and the newest advancements in liver imaging have improved the diagnosis of both overt malignancies and premalignant lesions, such as cirrhotic or dysplastic nodules, which is crucial to improve overall patient survival rate and to choose the best treatment options. The role of Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) has grown in the last 20 years. In particular, the introduction of hepatospecific contrast agents has strongly increased the definition of precursor nodules and detection of high-grade dysplastic nodules and early HCCs. Nevertheless, the diagnosis of liver tumours in cirrhotic patients sometimes remains challenging for radiologists, thus, in doubtful cases, biopsy and histological analysis become critical in clinical practice. This current review briefly summarizes the history of imaging and histology for HCC, covering the newest techniques and their limits. Then, the article discusses the links between radiological and pathological characteristics of liver lesions in cirrhotic patients, by describing the multistep process of hepatocarcinogenesis. Explaining the evolution of pathologic change from cirrhotic nodules to malignancy, the list of analyzed lesions provides regenerative nodules, low-grade and high-grade dysplastic nodules, small HCC and progressed HCC, including common subtypes (steatohepatitic HCC, scirrhous HCC, macrotrabecular massive HCC) and more rare forms (clear cell HCC, chromophobe HCC, neutrophil-rich HCC, lymphocyte-rich HCC, fibrolamellar HCC). The last chapter covers the importance of the new integrated morphological-molecular classification and its association with radiological features.

Long-term outcomes of living-donor liver transplantation, hepatic resection, and local therapy for hepatocellular carcinoma with three

Background and AimTreatment for small hepatocellular carcinoma (HCC) is determined based on the results of a liver function test and the tumor location and spread. The present study compared the outcomes among local therapy, hepatic resection (HR), and living‐donor liver transplantation (LDLT) for small HCC in a single institute.MethodsWe compared the overall survival, recurrence‐free survival, and cancer‐specific survival rates in patients with three HCC nodules <3 cm in size among local therapy, which included radiofrequency ablation (RFA), percutaneous ethanol injection (PEI), and transarterial chemoembolization (TACE), and surgical treatment (HR and LDLT).ResultsOne hundred and ninety‐seven patients with local therapy (109 RFA, 26 PEI, and 78 TACE), 107 with HR, and 66 with LDLT were enrolled in this study. There was no significant difference in OS among these groups. The recurrence‐free, cancer‐specific survival (CSS) of LDLT was superior to local therapy and HR. The prognostic factors for the survival were Child–Pugh (CP) Grade B and tumor marker for local therapy and multiple tumors and elevated ALT levels for HR.ConclusionsFor CP grade B patients with HCC of three <3‐cm nodule, LDLT could be considered because it resulted in better survival and CSS rates than local therapy.

Transcatheter arterial chemoembolization alone versus combined with microwave ablation for recurrent small hepatocellular carcinoma after resection: a retrospective comparative study

PurposeTo compare the efficacy and safety of transcatheter arterial chemoembolization combined with microwave ablation (TACE–MWA) versus TACE alone for the treatment of recurrent small hepatocellular carcinoma (sHCC) after resection.Materials and methodsFrom June 2015 to January 2020, a total of 45 patients with recurrent sHCC (size ≤ 3 cm) treated by TACE–MWA or TACE were included in this study. The radiological response at 1-, 3-, 6-month after initial treatment [modified Response Evaluation Criteria in Solid Tumors (mRECIST)], progression-free survival (PFS), overall survival (OS), and complications were evaluated.ResultsThe TACE–MWA group showed better 1-, 3-, 6-month tumor response rates than TACE group. The corresponding 1-, 3-, and 5-year PFS rates were 76.5%, 70.6%, and 70.6% for the TACE–MWA group, and 56.1%, 15.0%, and 15.0% for the TACE group (P = 0.003). The 1-, 3-, and 5-year OS rates were 100.0%, 82.1%, and 61.5% for the TACE–MWA group, and 89.0%, 58.1%, and 50.8% for the TACE group (P = 0.389), respectively. Moreover, no major complications related to treatment were observed in either of the groups. Compared with the TACE group, the TACE–MWA group had a significantly lower number of re-TACE sessions (P = 0.003).ConclusionsAlthough TACE alone provides equivalent effectiveness for recurrent sHCC in terms of OS rates, TACE–MWA had better 1-, 3-, 6-month tumor response rates and may prolong tumor PFS time.

Quantitative dual-energy computed tomography texture analysis predicts the response of primary small hepatocellular carcinoma to radiofrequency ablation

BackgroundRadiofrequency ablation (RFA) is one of the effective therapeutic modalities in patients with hepatocellular carcinoma (HCC). However, there is no proper method to evaluate the HCC response to RFA. This study aimed to establish and validate a clinical prediction model based on dual-energy computed tomography (DECT) quantitative-imaging parameters, clinical variables, and CT texture parameters. MethodsWe enrolled 63 patients with small HCC. Two to four weeks after RFA, we performed DECT scanning to obtain DECT-quantitative parameters and to record the patients’ clinical baseline variables. DECT images were manually segmented, and 56 CT texture features were extracted. We used LASSO algorithm for feature selection and data dimensionality reduction; logistic regression analysis was used to build a clinical model with clinical variables and DECT-quantitative parameters; we then added texture features to build a clinical-texture model based on clinical model. ResultsA total of six optimal CT texture analysis (CTTA) features were selected, which were statistically different between patients with or without tumor progression (P < 0.05). When clinical variables and DECT-quantitative parameters were included, the clinical models showed that albumin-bilirubin grade (ALBI) [odds ratio (OR) = 2.77, 95% confidence interval (CI): 1.35-6.65, P = 0.010], λAP (40-100 keV) (OR = 3.21, 95% CI: 3.16-5.65, P = 0.045) and ICAP (OR = 1.25, 95% CI: 1.01-1.62, P = 0.028) were associated with tumor progression, while the clinical-texture models showed that ALBI (OR = 2.40, 95% CI: 1.19-5.68, P = 0.024), λAP (40-100 keV) (OR = 1.43, 95% CI: 1.10-2.07, P = 0.019), and CTTA-score (OR = 2.98, 95% CI: 1.68-6.66, P = 0.001) were independent risk factors for tumor progression. The clinical model, clinical-texture model, and CTTA-score all performed well in predicting tumor progression within 12 months after RFA (AUC = 0.917, 0.962, and 0.906, respectively), and the C-indexes of the clinical and clinical-texture models were 0.917 and 0.957, respectively. ConclusionsDECT-quantitative parameters, CTTA, and clinical variables were helpful in predicting HCC progression after RFA. The constructed clinical prediction model can provide early warning of potential tumor progression risk for patients after RFA.

A multicenter, non-randomized, controlled trial to evaluate the efficacy of surgery versus radiofrequency ablation for small hepatocellular carcinoma (SURF-Cohort Trial): Analysis of overall survival.

4095 Background: We conducted a multicenter prospective study (SURF trial) to compare the efficacy of surgery vs. radiofrequency ablation (RFA) for small hepatocellular carcinoma (HCC). SURF trial consisted of a randomized controlled trial (SURF-RCT) and a non-randomized prospective observational study (SURF-Cohort), including patients who did not consent to randomization. The initial report of the SURF-Cohort trial showed that recurrence-free survival (RFS) did not differ significantly between patients undergoing surgery and RFA. The focus of the present report was to assess the efficacy for overall survival (OS). Methods: The SURF-Cohort trial was a prospective multicenter study conducted in 49 institutions in Japan. Patients (aged between 29 and 79 years) with Child-Pugh scores ≤ 7, largest HCC diameter ≤ 3 cm, and ≤ 3 HCC nodules were considered eligible. Before the enrollment, both liver surgeons and hepatologists who perform RFA confirm that all the patients can be treated using both surgery and RFA. The co-primary endpoints were RFS and OS. OS was assessed at 5 years after the last accrual as per the protocol. Inverse probability of treatment weighted (IPTW) analysis was used to balance the characteristics of the groups. This trial is registered in UMIN000001796. Results: During 2009–2015, 782 patients were enrolled. After excluding ineligible patients, the surgery and RFA groups included 382 and 371 patients, respectively. In the surgery group, median platelet count (13.7x104 vs. 11.5x104, P&lt; 0.01) was significantly greater, and the median largest HCC diameter was significantly greater (2.0 cm vs. 1.8 cm, P&lt; 0.01) than in the RFA group. The median (range) follow-up period was 6.8 years in the surgery group and 6.7 years in the RFA group. The IPTW-adjusted OS did not differ significantly between the surgery and RFA groups: the 5-year OS, 79.7% vs. 79.3%; HR 0.98; 95% CI 0.75–1.30; P= 0.906. The analysis after long-term follow-up in the current report showed that RFS was not significantly different between the surgery and RFA groups: the 5-year RFS, 44.6% vs. 39.3%; HR 0.86; 95% CI 0.71–1.06; P= 0.155. Conclusions: SURF-Cohort trial revealed that OS and RFS after the IPTW adjustment were not significantly different between patients undergoing surgery and RFA for early stage HCC (≤ 3 cm and 3 nodules). Clinical trial information: UMIN000001796.

Hyperspectral evaluation of liver oxygenation in a murine model of metabolic associated liver disease and hepatocellular carcinoma

Abstract Objective Untreated MAFLD is a continuum of disease ranging from hepatic steatosis to cirrhosis and hepatocellular carcinoma (HCC). Throughout the disease progression, a change in hepatic hemodynamics occurs as portal hypertension. Hepatic arterial buffer response is a compensatory mechanism to maintain liver perfusion facing reduction of portal flow. These changes could also impair hepatic oxygenation homeostasis. The aim of this study is to test this hypothesis in mouse models and to shed light on the oxygenation of fatty, portal hypertensive liver and its impact on HCC carcinogenesis. Methods C57BL/6 mice were fed a HFD starting from 4 weeks of age, porto-systemic shunts (or sham) were created at 8 weeks, and monitored up to 40 weeks. ND-fed non-shunted mice were used as control group. Hyperspectral imaging (HSI) was utilized to quantify tissue oxygenation (StO2) of ND, HFD and HFD-shunted mice. In a second set of experiment, we explored the role of a common hepatic artery ligation in the studied DEN-induced HFD mouse model. Results HFD induced hepatic steatosis and portal pressure compared to ND. Porto-systemic shunt could deviate about 67% of the portal flow through the spleen to the systemic circulation, thus reducing portal pressure close-to-normal levels. Compared to control mice, HFD feeding increased liver oxygenation (p=0.0004), while shunting restored a close to normal level (p&amp;lt;0.001). The oxygenation of small bowel is decreased in a similar manner in both HFD and HFD-shunted mice. In HFD-fed mice, artery ligation led to less carcinogenesis compared to mice without artery ligation (p=0.026). In addition, artery ligation was also associated with smaller HCCs (p=0.027). Conclusion Early stages of MAFLD alter hepatic oxygen homeostasis. Fatty liver, when associated to portal hypertension, express higher liver oxygenation levels, compared to control group. This could due to hepatocyte ballooning with a narrowing of portal system, thus bring portal hypertension state with a simultaneous arterial buffer response. Additionally, small bowel of portal hypertensive mice showed lower oxygen levels mirroring an intestinal venous congestion typical of portal hypertension. Oxygen deprivation, through artery ligation, decreases HCC carcinogenesis and reduces HCC nodules volume. Yet further research is needed but oxygen homeostasis seems play a role in MAFLD progression as well in HCC pathophysiology.

Abstract No. 261 Cost-effectiveness analysis of interventional liver-directed therapies for a single, small (< 3 cm) hepatocellular carcinoma in liver transplant candidates

In patients with a single hepatocellular carcinoma (HCC) ≤3 cm, locoregional therapy (LRT) is commonly performed while awaiting transplantation. The purpose is to assess the cost-effectiveness of the three main LRTs (transarterial chemoembolization (TACE), radioembolization (TARE), and percutaneous ablation) as bridging therapy.

Targeted Molecular Imaging Probes Based on Magnetic Resonance Imaging for Hepatocellular Carcinoma Diagnosis and Treatment

Hepatocellular carcinoma (HCC) is the sixth most commonly malignant tumor and the third leading cause of cancer-related death in the world, and the early diagnosis and treatment of patients with HCC is core in improving its prognosis. The early diagnosis of HCC depends largely on magnetic resonance imaging (MRI). MRI has good soft-tissue resolution, which is the international standard method for the diagnosis of HCC. However, MRI is still insufficient in the diagnosis of some early small HCCs and malignant nodules, resulting in false negative results. With the deepening of research on HCC, researchers have found many specific molecular biomarkers on the surface of HCC cells, which may assist in diagnosis and treatment. On the other hand, molecular imaging has progressed rapidly in recent years, especially in the field of cancer theranostics. Hence, the preparation of molecular imaging probes that can specifically target the biomarkers of HCC, combined with MRI testing in vivo, may achieve the theranostic purpose of HCC in the early stage. Therefore, in this review, taking MR imaging as the basic point, we summarized the recent progress regarding the molecular imaging targeting various types of biomarkers on the surface of HCC cells to improve the theranostic rate of HCC. Lastly, we discussed the existing obstacles and future prospects of developing molecular imaging probes as HCC theranostic nanoplatforms.

Complications after Thermal Ablation of Hepatocellular Carcinoma and Liver Metastases: Imaging Findings.

Tumour ablation is a strategy of treatment of hepatic tumours in patients with small hepatocellular carcinoma (HCC) (<3 cm) or in patients unfit for surgical resection. Moreover, tumor ablation can be used as an adjuvant therapy or may be used in association with resection in case of patients with poor functional liver disease. These types of treatment usually could be performed percutaneously under image guidance. The most clinically verified and used ablation modalities are Radiofrequency Ablation (RFA) and microwave ablation (MWA). However, despite both of them are considered minimally invasive techniques, they could be related to post-procedural complications. The International Working Group on Image-Guided Tumor and the Society of Interventional Radiology (SIR) identified major and minor post-ablative complications. Major complications, as vascular complications, occur in 2.2% to 3.1% of cases and include all the high risk pathological conditions which could increase the level of care or result in hospital admission or substantially prolonged hospital stay (SIR classifications C–E). Minor complications, as biliary complications, occur in 5% to 8.9% and include self-limiting conditions that are considered to be of low risk for the patient’s outcome. The purpose of this review is to summarise the main pathological ultrasound (US) and Computed Tomography (CT) findings, that may arise after ablative treatment. To simplify the analysis, the pathological pictures are divided according to the site of damage into vascular, biliary and extrahepatic complications.

Risk factors of residual tumor in single small hepatocellular carcinoma after thermal ablation treatment

Objective: To evaluate the risk factors of residual tumor after thermal ablation in patients with small hepatocellular carcinoma. Methods: This was a retrospective study recruiting 107 patients diagnosed as single hepatocellular carcinoma with maximum diameter ≤3 cm from December 2009 to August 2015 in National Cancer Center. The cohort enrolled 81 males and 26 females, including 83 patients younger than 70 years old. All patients were treated with radiofrequency ablation or microwave ablation, and evaluated by CT or MRI after 4-6 weeks compared with baseline data. Potentially related factors were analyzed such as patients' characteristics, tumor location and adjacent, ablation pattern, hepatitis B/C infection. A multivariate logistic regression analysis was conducted for the independence of risk factors. Results: Six patients (5.6%) with residual tumor was detected in the whole population of 101 cases. Univariate analysis suggested that tumor adjacent to vascular structure, poor differentiation, AFP≥200 μg/L were the risk factors of residue disease (all P<0.05). Multivariate logistic regression suggested that pathological type of poorly differentiated tumor was the only independent risk factor (HR=2.26,95%CI 0.25-20.50, P=0.030). Conclusions: Poorly differentiated pathology is an independent predictive factor for residual disease in small hepatocellular carcinoma after thermal ablation. Such patients should be routinely followed up after operation.

Laparoscopic liver resection versus percutaneous radiofrequency ablation for single small hepatocellular carcinoma (≤ 3 cm): Optimal indication based on the tumor size and the level of PIVKA-II

Laparoscopic liver resection versus percutaneous radiofrequency ablation for single small hepatocellular carcinoma (≤ 3 cm): Optimal indication based on the tumor size and the level of PIVKA-II

The role of neoadjuvant conventional transarterial chemoembolization with radiofrequency ablation in the treatment of recurrent hepatocellular carcinoma after initial hepatectomy with microvascular invasion

Objectives Recurrent hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI)-positive primary tumor is at high risk of re-recurrence while treated with radiofrequency ablation (RFA). We aimed to investigate whether neoadjuvant conventional transarterial chemoembolization (cTACE) was effective in reducing re-recurrence after RFA for recurrent HCC patients with MVI-positive primary tumors. Methods In this retrospective multicenter study, 468 patients with solitary small recurrent HCC (≤3.0cm) underwent RFA alone (n = 322) or with neoadjuvant cTACE (n = 146) between June 2007 and December 2017 were included. Overall survival (OS) and recurrence-free survival (RFS) were compared. Results The 1-, 5-year OS rates were 74.8%, 42.5% for RFA with neoadjuvant cTACE group, and 53.5%, 28.7% for RFA group (P < 0.001). The corresponding RFS rates were 51.7%, 24.4% for RFA with neoadjuvant cTACE group, and 36.1%, 9.3% for RFA group (P < 0.001). In subgroup analyses, the OS and RFS for neoadjuvant cTACE group were longer than those for RFA group no matter tumor size > 2cm (HR = 0.52, 95% CI: 0.36–0.77; HR = 0.49, 95% CI: 0.36–0.67) or not (HR = 0.53, 95% CI: 0.32–0.88; HR = 0.65, 95% CI: 0.42–0.98), or the time interval of recurrence from initial treatment ≤ 1 year (HR = 0.53, 95% CI: 0.36–0.77; HR = 0.70, 95% CI: 0.52–0.94) or not (HR = 0.56, 95% CI: 0.34–0.95; HR = 0.39, 95% CI: 0.25–0.62). Multivariable analyses showed that RFA alone (HR = 1.329, P = 0.031; HR = 1.764, P = 0.004) and interval of recurrence from initial treatment > 1 year(HR = 0.642, P = 0.001; HR = 0.298, P = 0.037) were independent prognostic factors of OS and RFS. Conclusions Neoadjuvant cTACE could effectively reduce re-recurrence after RFA, and improve the long-term survivals for patients with solitary small recurrent HCC whose primary tumor was MVI-positive. Key points For recurrent hepatocellular carcinoma (HCC) patients whose primary tumor was positive for microvascular invasion, neoadjuvant conventional transarterial chemoembolization (cTACE) with radiofrequency ablation (RFA) achieved better efficacy. Multivariable analyses showed that the interval of recurrence from initial treatment > 1 year and RFA alone were independent prognostic factors of overall survival and recurrence-free survival, respectively.

Liver resection for large and huge hepatocellular carcinoma: Predictors of failure, recurrence patterns, and prognoses.

Characteristic symptoms and signs are often absent in patients with hepatocellular carcinoma (HCC). As a result, many patients are not diagnosed until their tumors have grown to large (>5cm) or huge sizes (>10cm). Liver resection has traditionally been reserved for patients with small HCC, but more recently it is being used for patients with large and huge tumors. The aim of this study was to determine risk predictors of recurrence, patterns of recurrence, and survival rates for large and huge HCC patients who underwent curative liver resection. We retrospectively identified a subgroup of patients who underwent liver resection for HCC with diameters 5cm or larger. Overall survival (OS) and recurrence-free survival (RFS) rates were calculated using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were performed to investigate potential risk factors for recurrence and death. Among 897 patients, the median follow-up was 48 (range, 5-140) months. The 1-, 3-, and 5-year RFS rates were 51.6%, 36.1%, and 30.1%, respectively, and OS rates were 80.2%, 55.4%, and 47.7%, respectively. Significant independent predictors of recurrence were preoperative satellite nodule (HR=2.25; 95% CI, 1.17-4.31; p=.02), preoperative AFP levels above 400ng/ml (HR=1.23; 95% CI, 1.04-1.45; p=.01), resection margins of 1cm or less (HR=1.21; 95% CI, 1.00-1.46; p=.047), cirrhosis (HR=2.64; 95% CI, 2.13-3.28; p<.001), and microvascular invasion (HR=1.71; 95% CI, 1.45-2.20; p<.001). All of these except narrow resection margin were also independent risk factors of OS. Hepatic resection for patients with large and huge HCC without hepatic vascular invasion, extrahepatic metastases, or severe chronic liver disease results in acceptable long-term outcomes.

Percutaneous implantation of ethanol fueled catalytic hydrogel suppresses tumor growth by triggering ferroptosis

Percutaneous ethanol injection therapy (PEIT) is a nonthermal locoregional treatment modality widely used in the treatment of solid tumors such as small hepatocellular carcinoma (HCC). Restricted by the inhomogeneous diffusion and unwanted leakage of injected ethanol, PEIT that usually requires multiple injections is often associated with a high local recurrence rate and potential severe complications. Herein, we propose an alternative locoregional treatment strategy to effectively ablate tumors by utilizing the reactive oxygen species generated from the percutaneously implanted catalytic couple fueled by orally administrated ethanol. It is shown that the catalytic couple of alcohol oxidase and iron catalyst hemin conjugated chitosan can sequentially convert ethanol to cytotoxic hydrogen peroxides and then hydroxyl radials, thereby result in efficient cancer cell killing by triggering ferroptosis. Upon being fixed inside tumors with in-situ formed alginate hydrogels, such catalytic couple together with multiple ethanol gavages shows great inhibitory effect on murine H22 liver and 4T1 breast tumors, comparable to those treated by PEIT. The efficient therapeutic potency of the combination treatment is further confirmed in a rat orthotopic N1S1 HCC model. This work highlights that our ‘alcohol drinking’ anti-tumor strategy is of great effectiveness, operation convenience, and high safety.

Automatically Extracted Machine Learning Features from Preoperative CT to Early Predict Microvascular Invasion in HCC: The Role of the Zone of Transition (ZOT).

Simple SummaryMicrovascular invasion (MVI) is a universally recognised predictor of hepatocellular carcinoma (HCC) recurrence after curative treatments, whose diagnosis, nowadays, is still postponed to surgery, through histopathological specimen investigation. This retrospective study aims to exploit a radiomic approach to pre-procedural diagnosis MVI in early-stage HCC, with a diameter ≤ 3 cm. The main novelty of the study is the use of the zone of transition (ZOT), crossing tumour and peritumour, detected adaptively through a standardized procedure based on the analysis of image gradients. After generating radiomics features from ZOT and tumour core in arterial and venous computed tomography phases, a classifier is trained and validated using a signature of four features only. The achieved radiomic model enables the early diagnosis of small HCC (≤3 cm) showing MVI with high specificity (82%) and sensitivity (79%), perspectively providing an effective tool to detect the best candidates for surgical treatment and liver transplantation (negative predictive value = 87%).Background: Microvascular invasion (MVI) is a consolidated predictor of hepatocellular carcinoma (HCC) recurrence after treatments. No reliable radiological imaging findings are available for preoperatively diagnosing MVI, despite some progresses of radiomic analysis. Furthermore, current MVI radiomic studies have not been designed for small HCC nodules, for which a plethora of treatments exists. This study aimed to identify radiomic MVI predictors in nodules ≤3.0 cm by analysing the zone of transition (ZOT), crossing tumour and peritumour, automatically detected to face the uncertainties of radiologist’s tumour segmentation. Methods: The study considered 117 patients imaged by contrast-enhanced computed tomography; 78 patients were finally enrolled in the radiomic analysis. Radiomic features were extracted from the tumour and the ZOT, detected using an adaptive procedure based on local image contrast variations. After data oversampling, a support vector machine classifier was developed and validated. Classifier performance was assessed using receiver operating characteristic (ROC) curve analysis and related metrics. Results: The original 89 HCC nodules (32 MVI+ and 57 MVI−) became 169 (62 MVI+ and 107 MVI−) after oversampling. Of the four features within the signature, three are ZOT heterogeneity measures regarding both arterial and venous phases. On the test set (19MVI+ and 33MVI−), the classifier predicts MVI+ with area under the curve of 0.86 (95%CI (0.70–0.93), p∼10), sensitivity = 79% and specificity = 82%. The classifier showed negative and positive predictive values of 87% and 71%, respectively. Conclusions: The classifier showed the highest diagnostic performance in the literature, disclosing the role of ZOT heterogeneity in predicting the MVI+ status.

Prediction of early recurrence of hepatocellular carcinoma after resection based on Gd-EOB-DTPA enhanced magnetic resonance imaging: a preliminary study.

Early recurrence (ER) after radical resection of hepatocellular carcinoma (HCC) affects the prognosis of patients. Gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) can improve the detection rate of small HCC. This study innovatively introduces a new quantitative index combined with qualitative index to compare the differences in clinical and imaging characteristics between ER and non-ER groups and evaluate the feasibility of Gd-EOB-DTPA-enhanced MRI in predicting ER. A total of 68 patients with HCC confirmed by operation and pathology in the Shandong Cancer Hospital and Institute were included retrospectively. All participants were examined by Gd-EOB-DTPA-enhanced MRI within 3 weeks before surgery. Regular follow-up was performed every 2 months within 1 year after operation. Among them, 18 cases with new lesions were in ER group, and 50 cases without new lesions were in non-ER group. The clinical and imaging data of the 2 groups were collected, and the differences of clinical data and preoperative MRI signs between the ER group and non-ER group were compared. The predictive factors of ER after HCC were analyzed by multivariate logistic regression. The quantitative parameter lesion-to-liver contrast enhancement ratio (LLCER) can predict the pathological grade of HCC (P=0.023). The results of univariate analysis between the ER group and non-ER group showed that there were significant differences in pathological grade (P=0.008), lesion morphology (P=0.011), peritumoral low signal intensity in hepatobiliary phase (HBP) (P<0.001), satellite nodules (P<0.001), and LLCER (P<0.001) between the 2 groups. Multivariate logistic regression analysis showed that HBP peritumoral low signal intensity [odds ratio (OR) =7.214, 95% confidence interval (CI): 1.230-42.312, P=0.029], satellite nodules (OR =9.198, 95% CI: 1.402-60.339, P=0.021), and parameter LLCER value (OR =0.906, 95% CI: 0.826-0.995, P=0.039) were independent predictors of ER of HCC after resection. Preoperative Gd-EOB-DTPA enhanced MRI has important predictive value for early recurrence after radical resection of hepatocellular carcinoma.

The clinical value of dual-energy computed tomography and diffusion-weighted imaging in the context of liver cancer: A narrative review.

The dual-energy computed tomography (DECT) and diffusion-weighted magnetic resonance imaging (DWI-MRI) are used to diagnose liver cancer. The clinical value of these two examination methods needs to be further summarized. We collected and summarized relevant literature published from 2011 to 2021. The diagnostic performance of DECT was assessed between conventional computed tomography and DWI-MRI. DWI-MRI had a 69% sensitivity for detecting small hepatocellular carcinoma (HCC) lesions and a 60% diagnostic specificity for differentiating between types of HCC lesions. DECT had a sensitivity to small liver lesions (<1cm) of 69%, and the diagnostic specificity for HCC and metastasis was about 60%. DWI was more sensitive (90.3% vs. 74.9%) and accurate (91.9% vs. 76.9%) in diagnosing HCC compared with conventional MRI sequencing. With the aid of contrast media, DWI-MRI had 90.0% specificity for detecting small HCCs (smaller than 1cm). Furthermore, DWI-MRI not only provided physicians with valuable diagnostic information but also delivered histological grading information, with 78% accuracy for all benign lesions and 71% for solid lesions. DECT had relatively high sensitivity and required a lower contrast medium dose. With standardized quantitative parameters, it can be an extremely useful tool for HCC surveillance. DWI-MRI is the preferred imaging process as it produces high-contrast images for supporting an early diagnosis (high sensitivity and specificity) and provides histological information using non-ionizing radiation.