Efficacy and Safety of Radiation Segmentectomy with 90Y Resin Microspheres for Hepatocellular Carcinoma.

Background Limited data are available on radiation segmentectomy (RS) for treatment of hepatocellular carcinoma (HCC) using yttrium 90 (90Y) resin microsphere doses determined by using a single-compartment medical internal radiation dosimetry (MIRD) model. Purpose To evaluate the efficacy and safety of RS treatment of HCC with 90Y resin microspheres using a single-compartment MIRD model and correlate posttreatment dose with outcomes. Materials and Methods This retrospective single-center study included adult patients with HCC who underwent RS with 90Y resin microspheres between July 2014 and December 2022. Posttreatment PET/CT and dosimetry were performed. Adverse events were assessed using the Common Terminology Criteria for Adverse Events, version 5.0. Per-lesion and overall response rates (ie, complete response [CR], objective response, disease control, and duration of response) were assessed at imaging using the Modified Response Evaluation Criteria in Solid Tumors, and overall survival (OS) was assessed using Kaplan-Meier analysis. Results Among 67 patients (median age, 69 years [IQR, 63-78 years]; 54 male patients) with HCC, median tumor absorbed dose was 232 Gy (IQR, 163-405 Gy). At 3 months, per-lesion and overall (per-patient) CR was achieved in 47 (70%) and 41 (61%) of 67 patients, respectively. At 6 months (n = 46), per-lesion rates of objective response and disease control were both 94%, and per-patient rates were both 78%. A total of 88% (95% CI: 79 99) and 72% (95% CI: 58, 90) of patients had a per-lesion and overall duration of response of 1 year or greater. At 1 month, a grade 3 clinical adverse event (abdominal pain) occurred in one of 67 (1.5%) patients. Median posttreatment OS was 26 months (95% CI: 20, not reached). Disease progression at 2 years was lower in the group that received 300 Gy or more than in the group that received less than 300 Gy (17% vs 61%; P = .047), with no local progression in the former group through the end of follow-up. Conclusion Among patients with HCC who underwent RS with 90Y resin microspheres, 88% and 72% achieved a per-lesion and overall duration of response of 1 year or greater, respectively, with one grade 3 adverse event. In patients whose tumors received 300 Gy or more according to posttreatment dosimetry, a disease progression benefit was noted. © RSNA, 2024 Supplemental material is available for this article.

SPONTANEOUS REGRESSION OF HEPATOCELLULAR CARCINOMA: FOCUSING IN THE ASSOCIATED RISK FACTORS.

BACKGROUND: Spontaneous regression (SR) is defined as the partial or complete disappearance of a tumor, in the absence of a specific treatment. Evidence of the SR in hepatocellular carcinoma (HCC) is rare. OBJECTIVE: The authors aimed to review all the cases of SR of HCC in two reference centers of Southern Brazil, highlighting the main characteristics. METHODS: Data of all patients with HCC were retrospectively reviewed looking for the occurrence of SR in patients from two tertiary centers in Southern Brazil, in the last five years. The diagnosis of cirrhosis was established according to clinical, laboratory and imaging data, as well as upper endoscopy or histopathological examination when necessary. The diagnosis of HCC was based on typical findings according to radiologic criteria (LIRADS) or histopathological examination. Spontaneous regression was defined as a partial or complete involution of a HCC in the absence of a specific therapy. RESULTS: From all cases of HCC in the last 5 years (n=433), there were five cases of SR. Three (60%) were men, the mean age was 62.6 (50.0-76.0) years, and the etiology was HCV in 3 (60%). Complete regression was observed in three patients (60%), one patient (20%) presented partial regression, and one (20%) relapesed and died. The time of follow-up varied between 12 and 21 months. In this presentation, it was highlighted one case of SR observed after COVID-19 infection in a patient with cirrhosis. The possible mechanisms involved in this situation were reviewed, emphasizing the most common like hypoxia and immunological. There were also one patient submitted to a surgical procedure as a possible fator involved and three patients without obvious risk factors. CONCLUSION: This phenomenon will possibly contribute to a better understanding of the pathophysiological mechanisms of HCC.

Hepatic perivascular epithelioid cell tumors: Benign, malignant, and uncertain malignant potential.

In 2013, the World Health Organization defined perivascular epithelioid cell tumor (PEComa) as "a mesenchymal tumor which shows a local association with vessel walls and usually expresses melanocyte and smooth muscle markers." This generic definition seems to better fit the PEComa family, which includes angiomyolipoma, clear cell sugar tumor of the lung, lymphangioleiomyomatosis, and a group of histologically and immunophenotypically similar tumors that include primary extrapulmonary sugar tumor and clear cell myomelanocytic tumor. Clear cell tumors with this immunophenotypic pattern have also had their malignant variants described. When localizing to the liver, preoperative radiological diagnosis has proven to be very difficult, and most patients have been diagnosed with hepatocellular carcinoma, focal nodular hyperplasia, hemangioma, or hepatic adenoma based on imaging findings. Examples of a malignant variant of the liver have been described. Finally, reports of malignant variants of these lesions have increased in recent years. Therefore, we support the use of the Folpe criteria, which in 2005 established the criteria for categorizing a PEComa as benign, malignant, or of uncertain malignant potential. Although they are not considered ideal, they currently seem to be the best approach and could be used for the categorization of liver tumors.

Noninvasive assessment of liver fibrosis can predict clinical outcomes at late follow-up after a sustained virological response in HCV patients?

OBJECTIVES: The primary objective was to evaluate Liver-Related Events (LREs), including hepatic decompensation (ascites, hemorrhagic varices and encephalopathy) and Hepatocellular Carcinoma (HCC), as well as changes in liver stiffness during the follow-up period among patients who achieved a Sustained Virological Response (SVR) after treatment for chronic Hepatitis C Virus (HCV) infection. METHODS: A total of 218 patients with HCV were treated, and those who achieved an SVR were followed up for 3-years. Transient Elastography (TE) using FibroScan® was performed at various time points: before treatment, at the end of treatment, at 6-months post-treatment, at 1-year post-treatment, at 2-years post-treatment, and at 3-years post-treatment. RESULTS: At 6-months post-treatment, a Liver Stiffness Measurement (LSM) cutoff of > 19 KPa was identified, leading to a 14.5-fold increase in the hazard of negative outcomes, including decompensation and/or HCC. The analysis of relative changes in liver stiffness between pre-treatment and 6-months posttreatment revealed that a reduction in LSM of -10 % was associated with a -12 % decrease in the hazard of decompensation and/or HCC, with this trend continuing as the LSM reduction reached -40 %, resulting in a -41 % hazard of decompensation and/or HCC. Conversely, an increase in the relative change during this period, such as an LSM increase of +10 %, led to a + 14 % increase in the hazard of decompensation. In cases where this relative change in LSM was +50 %, the hazard of decompensation increased to +92. CONCLUSION: Transient elastography using FibroScan® can be a good tool for monitoring HCV patients with SVR after treatment to predict LREs in the long term.

Role of peritumoral tissue analysis in predicting characteristics of hepatocellular carcinoma using ultrasound-based radiomics.

Predicting the biological characteristics of hepatocellular carcinoma (HCC) is essential for personalized treatment. This study explored the role of ultrasound-based radiomics of peritumoral tissues for predicting HCC features, focusing on differentiation, cytokeratin 7 (CK7) and Ki67 expression, and p53 mutation status. A cohort of 153 patients with HCC underwent ultrasound examinations and radiomics features were extracted from peritumoral tissues. Subgroups were formed based on HCC characteristics. Predictive modeling was carried out using the XGBOOST algorithm in the differentiation subgroup, logistic regression in the CK7 and Ki67 expression subgroups, and support vector machine learning in the p53 mutation status subgroups. The predictive models demonstrated robust performance, with areas under the curves of 0.815 (0.683-0.948) in the differentiation subgroup, 0.922 (0.785-1) in the CK7 subgroup, 0.762 (0.618-0.906) in the Ki67 subgroup, and 0.849 (0.667-1) in the p53 mutation status subgroup. Confusion matrices and waterfall plots highlighted the good performance of the models. Comprehensive evaluation was carried out using SHapley Additive exPlanations plots, which revealed notable contributions from wavelet filter features. This study highlights the potential of ultrasound-based radiomics, specifically the importance of peritumoral tissue analysis, for predicting HCC characteristics. The results warrant further validation of peritumoral tissue radiomics in larger, multicenter studies.

Liver Imaging Reporting and Data System Contrast-Enhanced US Nonradiation Treatment Response Assessment Version 2024.

The American College of Radiology Liver Imaging Reporting and Data System (LI-RADS) standardizes the imaging technique, reporting lexicon, disease categorization, and management for patients with or at risk for hepatocellular carcinoma (HCC). LI-RADS encompasses HCC surveillance with US; HCC diagnosis with CT, MRI, or contrast-enhanced US (CEUS); and treatment response assessment (TRA) with CT or MRI. LI-RADS was recently expanded to include CEUS TRA after nonradiation locoregional therapy or surgical resection. This report provides an overview of LI-RADS CEUS Nonradiation TRA v2024, including a lexicon of imaging findings, techniques, and imaging criteria for posttreatment tumor viability assessment. LI-RADS CEUS Nonradiation TRA v2024 takes into consideration differences in the CEUS appearance of viable tumor and posttreatment changes within and in close proximity to a treated lesion. Due to the high sensitivity of CEUS to vascular flow, posttreatment reactive changes commonly manifest as areas of abnormal perilesional enhancement without washout, especially in the first 3 months after treatment. To improve the accuracy of CEUS for nonradiation TRA, different diagnostic criteria are used to evaluate tumor viability within and outside of the treated lesion margin. Broader criteria for intralesional enhancement increase sensitivity for tumor viability detection. Stricter criteria for perilesional enhancement limit miscategorization of posttreatment reactive changes as viable tumor. Finally, the TRA algorithm reconciles intralesional and perilesional tumor viability assessment and assigns a single LI-RADS treatment response (LR-TR) category: LR-TR nonviable, LR-TR equivocal, or LR-TR viable.

Prognostication of Hepatocellular Carcinoma Using Artificial Intelligence.

Hepatocellular carcinoma (HCC) is a biologically heterogeneous tumor characterized by varying degrees of aggressiveness. The current treatment strategy for HCC is predominantly determined by the overall tumor burden, and does not address the diverse prognoses of patients with HCC owing to its heterogeneity. Therefore, the prognostication of HCC using imaging data is crucial for optimizing patient management. Although some radiologic features have been demonstrated to be indicative of the biologic behavior of HCC, traditional radiologic methods for HCC prognostication are based on visually-assessed prognostic findings, and are limited by subjectivity and inter-observer variability. Consequently, artificial intelligence has emerged as a promising method for image-based prognostication of HCC. Unlike traditional radiologic image analysis, artificial intelligence based on radiomics or deep learning utilizes numerous image-derived quantitative features, potentially offering an objective, detailed, and comprehensive analysis of the tumor phenotypes. Artificial intelligence, particularly radiomics has displayed potential in a variety of applications, including the prediction of microvascular invasion, recurrence risk after locoregional treatment, and response to systemic therapy. This review highlights the potential value of artificial intelligence in the prognostication of HCC as well as its limitations and future prospects.

The Future Role of Abdominal US in Hepatocellular Carcinoma Surveillance.

Abdominal US is currently the best-validated surveillance strategy for hepatocellular carcinoma (HCC) in at-risk patients. It is the only modality shown to have completed all five phases of validation and can achieve high sensitivity and specificity for HCC detection, especially when conducted by expert sonographers in high-volume centers. However, US also has limitations, including operator dependency and varying sensitivity in clinical practice. Further, the sensitivity of US for early-stage HCC detection is lower in patients with obesity or nonviral liver disease, increasingly common populations undergoing surveillance. Imaging-based and blood-based surveillance strategies, including abbreviated MRI and biomarker panels, may overcome some limitations of US-based surveillance. Both strategies have promising test performance in phase II and phase III biomarker studies and are undergoing prospective validation. Considering the variation in HCC risk and test performance between patients, there will likely be a shift away from a one-size-fits-all approach and toward precision screening, in which the "best" test is selected based on individual patient characteristics. In this upcoming era of precision HCC screening among patients with cirrhosis, US will likely continue to have an important, albeit reduced, surveillance role.

Microinvasion in hepatocellular carcinoma: predictive factor and application for definition of clinical target volume for radiotherapy.

BACKGROUND: To investigate the correlation between microinvasion and various features of hepatocellular carcinoma (HCC), and to clarify the microinvasion distance from visible HCC lesions to subclinical lesions, so as to provide clinical basis for the expandable boundary of clinical target volume (CTV) from gross tumor volume (GTV) in the radiotherapy of HCC. METHODS: HCC patients underwent hepatectomy of liver cancer in our hospital between July 2019 and November 2021 were enrolled. Data on various features and tumor microinvasion distance were collected. The distribution characteristics of microinvasion distance were analyzed to investigate its potential correlation with various features. Tumor size compared between radiographic and pathologic samples was analyzed to clarify the application of pathologic microinvasion to identify subclinical lesions of radiographic imaging. RESULTS: The average microinvasion distance was 0.6 mm, with 95% patients exhibiting microinvasion distance less than 3.0 mm, and the maximum microinvasion distance was 4.0 mm. A significant correlation was found between microinvasion and liver cirrhosis (P = 0.036), serum albumin level (P = 0.049). Multivariate logistic regression analysis revealed that HCC patients with cirrhosis had a significantly lower risk of microinvasion (OR = 0.09, 95%CI = 0.02 ~ 0.50, P = 0.006). Tumor size was overestimated by 1.6 mm (95%CI=-12.8 ~ 16.0 mm) on radiographic size compared to pathologic size, with a mean %Δsize of 2.96% (95%CI=-0.57%~6.50%). The %Δsize ranged from - 29.03% to 34.78%. CONCLUSIONS: CTV expanding by 5.4 mm from radiographic GTV could include all pathologic microinvasive lesions in the radiotherapy of HCC. Liver cirrhosis was correlated with microinvasion and were independent predictive factor of microinvasion in HCC.

Screening for exclusion of high-risk bleeding features of esophageal varices in cirrhosis through CT and MRI.

BACKGROUND & AIM: Esophageal varices (EV) screening guidelines have evolved with improved risk stratification to avoid unnecessary esophagogastroduodenoscopy (EGD) in individuals with low bleeding risks. However, uncertainties persist in the recommendations for certain patient groups, particularly those with hepatocellular carcinoma (HCC) and/or receiving non-selective beta-blockers (NSBB) without prior endoscopy. This study assessed the efficacy of imaging in ruling out EVs and their high-risk features associated with bleeding in patients with cirrhosis and with HCC. We also evaluated the impact of NSBB on the detection of these characteristics. METHODS: A total of 119 patients undergoing EGD with CT and/or MRI within 90 days of the procedure were included. 87 patients had HCC. A new imaging grading system was developed utilizing the size of EVs and the extent of their protrusion into the esophagus lumen. The negative predictive value (NPV) of EVimaging(-) versus EVimaging (+) (grades 1-3) in ruling out the presence of EV and/or high-risk features by EGD was calculated. The predictive performance of imaging was determined by logistic regression. RESULTS: The NPV of imaging for detecting EV and high-risk features was 81 % and 92 %, respectively. Among HCC patients, the NPV for EV and high-risk features was 80 % and 64 %, respectively. Being on NSBB didn't statistically impact the imaging detection of EV. Imaging was a better predictor of high-risk EGD findings than Child-Turcotte-Pugh scores. CONCLUSIONS: Our results suggest that imaging can effectively rule out the presence of EV and high-risk features during EGD, even in patients with HCC and/or receiving NSBB.

Early detection of HCC in patients with cirrhosis using AI; a Systematic Review.

Introduction: Hepatocellular carcinoma constitutes for approximately 75% of primary cancers of liver. Around 80- 90% of patients with HCC have cirrhosis at the time of diagnosis. Use of AI has recently gained significance in the field of hepatology, especially for the detection of HCC, owing to its increasing incidence and specific radiological features which have been established for its diagnostic criteria. Objectives: A systematic review was performed to evaluate the current literature for early diagnosis of hepatocellular carcinoma in cirrhotic patients. METHODS: Systematic review was conducted using PRISMA guidelines and the relevant studies were narrated in detail with assessment of quality for each paper. RESULTS: This systematic review displays the significance of AI in early detection and prognosis of HCC with the pressing need for further exploration in this field. CONCLUSIONS: AI can have a significant role in early diagnosis of HCC in cirrhotic patients.

Quick and easy assessment of sarcopenia in cirrhosis: Can ultrasound be the solution?

Cirrhosis is frequently associated with sarcopenia, with reported rates of over 80% in patients with decompensated alcohol-related liver disease. Sarcopenia negatively impacts the prognosis of cirrhotic patients and affects the response to treatment of patients with hepatocellular carcinoma (HCC). For these reasons, identifying an easy-to-perform method to assess sarcopenia in is a key element in the optimization of care in this patient population. Assessment of muscle mass by computed tomography is considered the standard of care for the diagnosis of sarcopenia, but exposure to radiation and high costs limit its application in this setting, especially for repeated assessments. We believe that ultrasound, a cheap and harmless technique also used for HCC screening in cirrhotic patients, could have an expanding role in the diagnosis and follow-up of sarcopenia in these patients.

A landmark-supervised registration framework for multi-phase CT images with cross-distillation.

Objective.Multi-phase computed tomography (CT) has become a leading modality for identifying hepatic tumors. Nevertheless, the presence of misalignment in the images of different phases poses a challenge in accurately identifying and analyzing the patient's anatomy. Conventional registration methods typically concentrate on either intensity-based features or landmark-based features in isolation, so imposing limitations on the accuracy of the registration process.Method.We establish a nonrigid cycle-registration network that leverages semi-supervised learning techniques, wherein a point distance term based on Euclidean distance between registered landmark points is introduced into the loss function. Additionally, a cross-distillation strategy is proposed in network training to further improve registration performance which incorporates response-based knowledge concerning the distances between feature points.Results.We conducted experiments using multi-centered liver CT datasets to evaluate the performance of the proposed method. The results demonstrate that our method outperforms baseline methods in terms of target registration error. Additionally, Dice scores of the warped tumor masks were calculated. Our method consistently achieved the highest scores among all the comparing methods. Specifically, it achieved scores of 82.9% and 82.5% in the hepatocellular carcinoma and the intrahepatic cholangiocarcinoma dataset, respectively.Significance.The superior registration performance indicates its potential to serve as an important tool in hepatic tumor identification and analysis.

Image-guided percutaneous strategies to improve the resectability of HCC: Portal vein embolization, liver venous deprivation, or radiation lobectomy?

Despite considerable advances in surgical technique, many patients with hepatic malignancies are not operative candidates due to projected inadequate hepatic function following resection. Consequently, the size of the future liver remnant (FLR) is an essential consideration when predicting a patient's likelihood of liver insufficiency following hepatectomy. Since its initial description 30 years ago, portal vein embolization has become the standard of care for augmenting the size and function of the FLR preoperatively. However, new minimally invasive techniques have been developed to improve surgical candidacy, chief among them liver venous deprivation and radiation lobectomy. The purpose of this review is to discuss the status of preoperative liver augmentation prior to resection of hepatocellular carcinoma with a focus on these three techniques, highlighting the distinctions between them and suggesting directions for future investigation.

Correlation of pathological examination with indocyanine green (ICG) intensity gradients: a prospective study in patients with liver tumor.

BACKGROUND: Intraoperative indocyanine green (ICG) fluorescence imaging has been shown to be a new and innovative way to illustrate the optimal resection margin in hepatectomy for hepatocellular carcinoma. This study investigated its accuracy in resection margin determination by looking into the correlation of ICG intensity gradients with pathological examination results of resected specimens. METHODS: This was a prospective, single-center, non-randomized controlled study. Patients who had liver tumors indicating liver resection were recruited. The hypothesis was that the use of intraoperative near-infrared/ICG fluorescence imaging would be a promising guiding tool for removing hepatocellular carcinoma with a better resection margin. Patients were given ICG (0.25 mg/kg) 1 day before operation. Resected specimens were inspected under a fluorescent imaging system. Biopsies were taken from tumors and normal tissue. Color signals obtained from ICG fluorescence imaging were compared with biopsies for analysis. RESULTS: Twenty-two patients were recruited for study. The median size of their tumors was 2.25 cm. One patient had resection margin involvement. Under ICG fluorescence, the tumors typically lighted up as yellow color, wrapped by a zone of green color. Tumors of 17 patients (77.3%) displayed yellow color and were confirmed malignancy, while tumors of 12 patients (54.5%) displayed green color and were confirmed malignancy. Receiver operating characteristic curve was used to measure the sensitivity and specificity of the green color to look for a clear resection margin. The area under the curve was 85.3% (p = 0.019, 95% confidence interval 0.696-1.000), with a sensitivity of 0.706 and specificity of 1.000. CONCLUSION: The use of ICG fluorescence can be helpful in determining resection margins. Resection of tumor should include complete resection of the green zone shown in the fluorescence image.

Based on Gadolinium Ethoxybenzyl DTPA-Enhanced MRI: Diagnostic Performance of the Category-Modified LR-5 Criteria in Patients At Risk for Hepatocellular Carcinoma.

Introduction: We aimed to modify the LR-5 strategy to improve the diagnostic sensitivity for hepatocellular carcinoma (HCC) in high-risk patients while maintaining specificity. Methods: This study retrospectively analyzed 412 patients with 445 liver observations who underwent preoperative gadolinium ethoxybenzyl DTPA (GD-EOB-DTPA)-enhanced MRI followed by surgical procedures or biopsies. All observations were classified according to LI-RADS v2018, and the classifications were adjusted by modifying major features (MF)(substituting threshold growth with a more HCC-specific ancillary features (AF): presence of blood products within the mass, arterial phase hyperenhancement (APHE) was interpreted with hypointensity on precontrast imaging- isointensity in arterial phase (AP) and extending washout to transitional phase (TP)(2 min)). The specificity, sensitivity, and positive predictive value (PPV) were assessed to compare LR-5 (definitely HCC) diagnostic efficacy between LI-RADS version 2018 and modified LI-RADS. Results: Apart from nonenhancing "capsule", the interreader agreement of MFs and HCC-specific AFs between the two readers reached substantial or excellent ranges (κ values ranging from 0.631 to 0.911). According to LI-5 v2018, the specificity, sensitivity and PPV of HCC were 90.74%, 82.35%, and 98.17%, respectively. Based on a more HCC-specific AF, signal intensity in AP and TP (2 min), the sensitivity of the three modified strategies were 86.19%, 93.09%, 96.67% (P < .05)), while maintaining high specificity and PPV rates at 88.89% and 98.25% (P > .05) Conclusion: Further investigation into the efficacy of threshold growth as a MF is warranted. By utilizing GD-EOB-DTPA-enhanced MRI, enhancing the sensitivity of the modified LR-5 category may be achieved without compromising specificity and PPV in diagnosing HCC among high-risk patients.

Value of Sonazoid-enhanced ultrasonography in characterizing indeterminate focal liver lesions on gadoxetic acid-enhanced liver MRI in patients without risk factors for hepatocellular carcinoma.

PURPOSE: To evaluate the added value of contrast-enhanced ultrasonography (CEUS) using Sonazoid in characterizing focal liver lesions (FLLs) with indeterminate findings on gadoxetic acid-enhanced liver MRI in patients without risk factors for hepatocellular carcinoma (HCC). METHODS: Patients who underwent CEUS using Sonazoid for characterizing indeterminate FLLs on gadoxetic acid-enhanced liver MRI were. The indeterminate FLLs were classified according to the degree of malignancy on a 5-point scale on MRI and combined MRI and CEUS. The final diagnosis was made either pathologically or based on more than one-year follow-up. The diagnostic performance was assessed using a receiver operating characteristic (ROC) curve analysis, and the net reclassification improvement (NRI) was calculated. RESULTS: A total of 97 patients (mean age, 49 years ± 16, 41 men, 80 benign and 17 malignant lesions) were included. When CEUS was added to MRI, the area under the ROC curve increased, but the difference was not statistically significant (0.87 [95% confidence interval {CI}, 0.77-0.98] for MRI vs 0.93 [95% CI, 0.87-0.99] for CEUS added to MRI, P = 0.296). The overall NRI was 0.473 (95% CI, 0.100-0.845; P = 0.013): 33.8% (27/80) of benign lesions and 41.2% (7/17) of malignant lesions were appropriately reclassified, whereas 10.0% (8/80) of benign lesions and 17.6% (3/17) of malignant lesions were incorrectly reclassified. CONCLUSIONS: Although performing CEUS with Sonazoid did not significantly improve the overall diagnostic performance in characterizing indeterminate FLLs on gadoxetic acid-enhanced liver MRI in patients without risk factors for HCC, it may increase radiologist's confidence in classifying FLLs.