Hepatocellular carcinoma (HCC) accounts for 90% of liver cancer cases worldwide and is currently the most quickly increasing cause of cancer-related deaths in the United States. The 5-year survival rate for primary liver cancer is estimated to be below 20%, and HCC mortality is expected to increase by 41% by 2040. Currently, surgical resection is the first-line approach to definitive treatment of early-stage HCC. However, the majority of patients present with late-stage, unresectable disease due to the asymptomatic nature of early HCC. For patients who present with unresectable HCC, locoregional therapies such as transarterial chemoembolization (TACE) represent an alternative approach to HCC treatment. TACE is a minimally invasive, catheter-based technique that allows for targeted delivery of chemotherapy to tumor sites while occluding tumor-feeding blood vessels. In appropriately selected patients, outcomes for TACE therapy have been shown to be more favorable than supportive care or conservative management. The increasing incidence and mortality of HCC, in addition to the late-stage presentation of most HCC patients, demonstrates the need to expand the role of locoregional therapies in the treatment of HCC. TACE represents an appealing approach to HCC management, including disease control, palliation, and potentially curative-intent strategies. In this review, we will describe the current utility of TACE in the treatment of HCC, characterize the outcomes of patients treated with TACE across different HCC stages, and outline future applications of TACE in the treatment paradigm.

UNASSIGNED: Primary liver tumors constitute one of the most common tumors. These are aggressive tumors with poor survival. Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), most commonly used functional imaging, shows limited tracer retention and poor tumor to background ratios (TBR). Novel 68Ga-fibroblast-activation-protein inhibitor (FAPI) PET/CT has shown better tracer uptake and detection efficacy in liver tumors. However, most of the available literature is limited to single center studies with limited number of patients. So, we tried to review and analyze the head-to-head comparison of 18F-FDG PET/CT and 68Ga-FAPI PET/CT in evaluation of liver tumors.
UNASSIGNED: Literature available on head to head comparison of diagnostic accuracy of 18F-FDG PET/CT and 68Ga-FAPI PET/CT was searched in databases like PubMed, SCOPUS, EMBASE and Google Scholar for published original studies till April 2023. The relevant studies were selected and assessed using the Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies-2 checklist. A random-effect model was used for calculating pooled sensitivity and specificity. They were represented with 95% confidence intervals (95% CI) and demonstrated in Forest plots. I-square statistic was used to assess heterogeneity in the studies.
UNASSIGNED: Pooled sensitivity and specificity of FAPI PET/CT and 18F-FDG PET/CT for detection of primary liver tumors was 94.3% (95% CI: 90.6-96.8%); 89.3% (95% CI: 71.8-97.7%) and 56.1% (95% CI: 49.7-62.5%); 96.4% (95% CI: 81.7-99.9%) respectively. Pooled sensitivity for detection of extrahepatic metastatic disease was 92.2% (range: 88.1-100%; 95% CI: 87.8-95.4%) and 72.4% (range: 69.8-76.5; 95% CI: 65.9-78.2%) respectively. Also, the maximum standardized uptake value (SUVmax) and TBR were higher for FAPI PET/CT than 18F-FDG PET/CT in the included studies.
UNASSIGNED: Overall, FAPI PET/CT showed higher sensitivity for detection of liver tumors with better SUVmax and TBR than 18F-FDG PET/CT.
UNASSIGNED: Primer karaciğer tümörleri en sık görülen tümörlerdendir. Bunlar hayatta kalma oranı düşük olan agresif tümörlerdir. En sık kullanılan fonksiyonel görüntüleme olan florodeoksiglukoz (FDG) pozitron emisyon tomografisi/bilgisayarlı tomografi (PET/BT), sınırlı radyofarmasötik tutulumu ve zayıf tümör/arka plan oranları (TBR) gösterir. Yeni 68Ga-fibroblast aktivasyon protein inhibitörü (FAPI) PET/BT, karaciğer tümörlerinde daha iyi radyofarmasötik tutulumu ve tespit etkinliği göstermiştir. Ancak mevcut literatürün çoğu, sınırlı hasta sayısıyla yapılan tek merkezli çalışmalarla sınırlıdır. Bu nedenle, karaciğer tümörlerinin değerlendirilmesinde 18F-FDG PET/BT ve 68Ga-FAPI PET/BT’nin birebir karşılaştırmasını gözden geçirip analiz etmeye çalıştık.
UNASSIGNED: 18F-FDG PET/BT ve 68Ga-FAPI PET/BT’nin tanısal doğruluğunun birebir karşılaştırılması konusunda mevcut literatür, Nisan 2023’e kadar yayınlanmış araştırma makaleleri için PubMed, SCOPUS, EMBASE ve Google Scholar gibi veritabanlarında tarandı. İlgili çalışmalar Tanısal Doğruluk Çalışmalarının Kalite Değerlendirmesi için Gözden Geçirilmiş Araç-2 kontrol listesi kullanılarak seçilmiş ve değerlendirilmiştir. Birleştirilmiş duyarlılığı ve özgüllüğü hesaplamak için rastgele etki modeli kullanıldı. Bunlar %95 güven aralıklarıyla (%95 GA) temsil edildi ve Orman grafiklerinde gösterildi. Çalışmalardaki heterojenliği değerlendirmek için I-kare istatistiği kullanıldı.
UNASSIGNED: Primer karaciğer tümörlerinin tespiti için FAPI PET/BT’nin havuzlanmış duyarlılığı ve özgüllüğü sırasıyla %94,3 (%95 GA: %90,6-96,8) ve %89,3 (%95 GA: %71,8-97,7); 18F-FDG PET/BT’nin havuzlanmış duyarlılığı ve özgüllüğü sırasıyla %56,1 (%95 GA: %49,7-62,5) ve %96,4 (%95 GA: %81,7-99,9) idi. Ekstrahepatik metastatik hastalığın saptanması için havuzlanmış duyarlılık FAPI PET/BT ve 18F-FDG PET/BT için sırasıyla %92,2 (aralık: %88,1-100; %95 GA: %87,8-95,4) ve %72,4 (aralık: 69,8-76,5; %95 GA: %65,9-78,2) idi. Ayrıca, dahil edilen çalışmalarda FAPI PET/BT için maksimum standardize tutulum değeri (SUVmaks) ve TBR, 18F-FDG PET/BT’den daha yüksekti.
UNASSIGNED: Genel olarak, FAPI PET/BT, karaciğer tümörlerinin tespitinde 18F-FDG PET/BT’ye göre daha iyi SUVmaks ve TBR ile daha yüksek duyarlılık gösterdi.

Tenofovir disoproxil fumarate (TDF) seems to prevent hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV). However, the mechanism is still little known. This study aimed to investigate the the roles and mechanisms of TDF, tenofovir alafenamide fumarate (TAF), and entecavir (ETV) on the malignant characteristics of liver cancer cells. Using the wound-healing assays, transwell assays, matrigel transwell assays, and cell counting kit-8 (CCK-8) assays, it was possible to identify that TDF/TAF, inhibited migration, invasion, and proliferation of HepG2 cells and Huh7 cells. To investigate the mechanisms, we performed TOP/FOP-Flash system, Western blot, and RT-qPCR assays of liver cancer cells cultured with TDF/TAF and found a lower activity of Wnt/β-catenin signaling pathway compared with control cells. Finally, Hepatitis C virus p7 trans-regulated protein 3 (p7TP3), a tumor suppressor in liver cancers, was significantly increased in HepG2 cells and Huh7 cells that treated with TDF/TAF. However, entecavir (ETV)-treated liver cancer cells showed no significant difference in the malignant characteristics of liver cancer cells, activity of Wnt/β-catenin signaling pathway, and expression of p7TP3, compared with the control groups. To conclude, TDF/TAF maybe novel promising therapeutic strategy for liver cancers, including HCC and hepatoblastoma, via Wnt/β-catenin signaling pathway, by up-regulating expression of the tumor suppressor, p7TP3.

UNASSIGNED: To investigate the efficacy and safety of microwave ablation (MWA) assisted by ultrasound fusion imaging (FI) for primary and secondary liver cancers with a diameter of 3-7 cm.
UNASSIGNED: A retrospective analysis was conducted on patients with primary and secondary liver cancers (3-7 cm) who underwent MWA with ultrasound FI assistance in our hospital from April 2020 to May 2022. Technical success, technique efficacy, local tumor progression (LTP), major complication, intrahepatic distant recurrence (IDR), and overall survival (OS) were assessed during the follow-up period. In addition, the ablation results of tumors between the medium-sized group (3.1-5.0 cm) and large-sized group (5.1-7.0 cm) were compared.
UNASSIGNED: 31 patients with 35 primary and secondary liver cancers were treated with MWA assisted by ultrasound FI. Complete ablation was achieved in 34 lesions with a technical success rate of 97.1%. Major complications occurred in 6.5% of patients (2/31), while no ablation-related deaths were reported. The median follow-up time of this study was 24 months (range:10 to 35 months). The technique efficacy rate was 97.1% (34/35), with LTP occurring in three lesions at a rate of 8.8% (3/34). The incidence of IDR was 38.7% (12/31) and the 2-year cumulative OS rate reached 96.7%. Moreover, there were no statistical differences in technique efficacy rate (p=0.286), LTP rate (p=0.328), major complication rate (p=0.503), IDR (p=0.857), and OS (p=0.118) between medium-sized group and large-sized group.
UNASSIGNED: Ultrasound FI-assisted MWA has the potential to be an effective and safe therapeutic strategy for primary and secondary liver cancers ranging from 3-7 cm in size.

Cholangiocarcinomas (CCAs) are a group of heterogeneous epithelial malignancies that can originate at the level of any location of the biliary tree. These tumors are relatively rare but associated with a high rate of mortality. CCAs are morphologically and molecularly heterogeneous and for their location can be distinguished as intracellular and extracellular, subdivided into perihilar and distal. Recent epidemiological, molecular, and cellular studies have supported that the consistent heterogeneity observed for CCAs may result from the convergence of various key elements mainly represented by risk factors, heterogeneity of the associated molecular abnormalities at genetic and epigenetic levels and by different potential cells of origin. These studies have consistently contributed to better defining the pathogenesis of CCAs and to identify in some instances new therapeutic targets. Although the therapeutic progress were still limited, these observations suggest that a better understanding of the molecular mechanisms underlying CCA in the future will help to develop more efficacious treatment strategies.

The combination of stereotactic body radiation therapy (SBRT) plus immune checkpoint inhibitors (ICI) must be explored to treat advanced primary liver tumors such as hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Limited retrospective reviews and case reports/series suggest this combination can be effective and safe in both cancer types. With ICIs moving into the first line (IMbrave 150, HIMALAYA, and TOPAZ-1) to manage these cancers, identifying a suitable population for this approach is challenging. Patients with macrovascular invasion (MVI)-positive HCC (especially if larger veins are involved) or recurrent HCCs post-locoregional therapies (such as transarterial radioembolization (TARE), transarterial chemoembolization (TACE), or ablation), as well as those ineligible for bevacizumab or tyrosine kinase inhibitors (TKIs), should be the focus of exploring this combination in HCC. Unresectable or oligometastatic CCA patients who cannot tolerate gemcitabine/cisplatin (GC) or those who progressed on GC without durvalumab and do not have targetable mutations could also be considered for this approach. In both HCC and CCA disease groups, SBRT plus ICI can be examined post-ICI as these two modalities act synergistically to enhance anti-tumor activity (based on pre-clinical studies). Large-scale randomized trials are needed to identify the subsets of primary liver cancers suitable for this approach and to clearly define its clinical benefit.

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver carcinoma displaying both hepatocytic and cholangiocytic differentiation within the same tumor. Relative to classic hepatocellular carcinoma (HCC), cHCC-CCA has more aggressive behavior and a poorer prognosis. Though recent advances have improved our understanding of the biology underlying cHCC-CCAs, they remain diagnostically challenging for pathologists because of their morphologic and phenotypic diversity. Accurate diagnosis of cHCC-CCA is important for patient management and prognostication. Herein, we review recent updates on cHCC-CCA, focusing on tumor classification, pathology, and diagnostic approach.

Hepatocellular carcinoma (HCC) represents a global health concern, particularly in Southeast Asia where hepatitis B virus (HBV) infection is common. In this study, we applied tissue-based proteomics to identify novel serological proteins for HCC and validated their performance in serum specimens.
In a discovery set, liver tissue specimens of HBV-related HCC, intrahepatic cholangiocarcinoma (iCCA) and colorectal cancer with liver metastasis (CRLM) were analyzed using mass spectrometry (LTQ-Orbitrap-XL). A subset of proteins that showed highly expressed in HCC were then confirmed by Western blotting. Additionally, clinical significance of selected candidate proteins was tested in serum samples of 80 patients with HBV-related HCC, 50 patients with HBV-related liver cirrhosis and 30 healthy controls.
Based on LTQ-Orbitrap-XL mass spectrometer, various differentially expressed proteins (DEPs) between tumor and adjacent non-tumor tissues were identified. These included 77 DEPs for HCC, 77 DEPs for iCCA and 55 DEPs for CRLM. Among selected candidate proteins, annexin A2 and cathepsin D were confirmed to be overexpressed in HCC tissue by Western blot analysis. In a validate cohort, serum cathepsin D level, but not annexin A2, was significantly higher in HCC compared with the non-HCC groups. Serum cathepsin D level was also positively correlated with tumor size and tumor stage. Additionally, the combined assay of serum cathepsin D and alpha-fetoprotein had a high sensitivity in detecting early HCC (83%) and intermediate/advanced HCC (96%). Moreover, patients with low serum cathepsin D (<305 ng/mL) displayed significantly better overall survival than those whose serum levels were high (≥305 ng/mL).
Proteomics and subsequent validation revealed cathepsin D as a novel biomarker for HCC. Apart from its diagnostic role, serum cathepsin D might also serve as a prognostic biomarker of HCC. Additional large-scale studies are needed to verify our findings.

Through a comprehensive review and in silico analysis of reported data on STAT-linked diseases, we analysed the communication pathways and interactome of the seven STATs in major cancer categories and proposed rational targeting approaches for therapeutic intervention to disrupt critical pathways and addictions to hyperactive JAK/STAT in neoplastic states. Although all STATs follow a similar molecular activation pathway, STAT1, STAT2, STAT4 and STAT6 exert specific biological profiles associated with a more restricted pattern of activation by cytokines. STAT3 and STAT5A as well as STAT5B have pleiotropic roles in the body and can act as critical oncogenes that promote many processes involved in cancer development. STAT1, STAT3 and STAT5 also possess tumour suppressive action in certain mutational and cancer type context. Here, we demonstrated member-specific STAT activity in major cancer types. Through systems biology approaches, we found surprising roles for EGFR family members, sex steroid hormone receptor ESR1 interplay with oncogenic STAT function and proposed new drug targeting approaches of oncogenic STAT pathway addiction.

OBJECTIVE: To test the hypothesis that 18F-fluorodeoxyglucose positron emission tomography and MRI (18F-FDG PET/MRI) can detect early residual tumor following radiofrequency ablation (RFA) of liver cancer using a VX2 tumor model.
METHODS: Twenty-four rabbits with VX2 liver tumors were randomly divided into three groups (n = 8/group): group 1 without RFA treatment, group 2 with complete ablation, and group 3 with partial ablation. 18F-FDG PET/MRI scan was obtained in three animal groups within 2 hours post-RFA. The maximum standardized uptake value (SUVmax) of non-treated liver tumor, benign peri-ablational enhancement (BPE), residual tumor, ablated tumor, adjacent liver parenchyma, and mean SUV of normal liver were measured, respectively. The ratios of SUVmax for these targets to mean SUV of normal liver (TNR) were calculated and statistically compared.
RESULTS: The mean TNR of non-treated liver tumors in group 1 was significantly greater than that of adjacent liver parenchyma (8.68 ± 0.71 vs 1.89 ± 0.26, p < 0.001). In group 2, the mean TNR of BPE was significantly greater than that of adjacent liver parenchyma (2.85 ± 0.20 vs 1.86 ± 0.25, p < 0.001). In group 3, the mean TNR of residual tumor was significantly greater than that of BPE (8.64 ± 0.59 vs 2.78 ± 0.23, p < 0.001), which was significantly greater than that of completely ablated tumor (2.78 ± 0.23 vs 0.50 ± 0.06, p < 0.001).
CONCLUSIONS: 18F-FDG PET/MRI may serve as a promising imaging tool for early detection of viable residual tumors due to incomplete tumor ablation.