BACKGROUND: In recent years, many studies have attempted to develop models to predict the recurrence of hepatocarcinoma after liver transplantation.
METHODS: A single-centre, retrospective cohort study analysed patients receiving transplants due to hepatocarcinoma during the 20 years of the transplant programme. We analysed patient survival, hepatocarcinoma recurrence and the influence of the different factors described in the literature as related to hepatocarcinoma recurrence. We compared the results of previous items between the first and second decades of the transplantation programme (1995-2010 and 2010-2020).
RESULTS: Of 265 patients, the patient survival rate was 68% at 5 years, 58% at 10 years, 45% at 15 years and 34% at 20 years. The overall recurrence rate of hepatocarcinoma was 14.5%, without differences between periods. Of these, 54% of recurrences occurred early, in the first two years after transplantation. Of the parameters analysed, an alpha-fetoprotein level of >16 ng/mL, the type of immunosuppression used and the characteristics of the pathological anatomy of the explant were significant. A trend towards statistical significance was identified for the number of nodules and the size of the largest nodule. Logistic regression analysis was used to develop a model with a sensitivity of 85.7% and a specificity of 35.7% to predict recurrences in our cohort. Regarding the comparison between periods, the survival and recurrence rates of hepatocarcinoma were similar. The impact of the factors analysed in both decades was similar.
CONCLUSIONS: Most recurrences occur during the first two years post-transplantation, so closer follow-ups should be performed during this period, especially in those patients where the model predicts a high risk of recurrence. The detection of patients at higher risk of recurrence allows for closer follow-up and may, in the future, make them candidates for adjuvant or neoadjuvant systemic therapies to transplantation.

BACKGROUND: Patients treated with direct-acting antivirals for hepatitis C exhibit high cure rates and improved survival. However, there is limited knowledge on their long-term clinical evolution.
OBJECTIVE: In this study, we aimed to analyse the risk of hepatocarcinoma and hepatic decompensation in patients treated with direct-acting antivirals.
METHODS: We conducted a retrospective single-centre study of Portuguese patients with advanced fibrosis treated with direct-acting antiviral agents between 2015 and 2022 at a tertiary hospital.
RESULTS: Out of 460 patients, 50 (10.9 %) developed hepatocarcinoma and 36 (7.8 %) experienced hepatic decompensation. The risk for hepatocarcinoma was higher in patients aged over 55 (HR 4.87, 95 % CI 2.34-10.13, p < 0.001), with signs of portal hypertension (HR 3.83, 95 % CI 2.05-7.13, p < 0.001) and arterial hypertension (HR 1.98, 95 % CI 1.09-3.58, p = 0.024). Alcohol consumption (HR 3.30, 95 % CI 1.22-8.94, p = 0.019), signs of portal hypertension (HR 4.56, 95 % CI 2.19-9.48, p < 0.001) and hepatocarcinoma (HR 3.47, 95 % CI 1.69-7.10, p < 0.001) increased the risk of hepatic decompensation.
CONCLUSIONS: Our study found a high incidence of hepatocarcinoma and hepatic decompensation, along with high mortality, in patients with advanced fibrosis treated with direct-acting antivirals. We identified risk factors such as arterial hypertension, alcohol consumption, and signs of portal hypertension, highlighting their role in clinical management and patient monitoring.

Over the past 10 years, the biological role of lipid droplets (LDs) has gained significant attention in the context of both physiological and pathological conditions. Considerable progress has been made in elucidating key aspects of these organelles, yet much remains to be accomplished to fully comprehend the myriad functions they serve in the progression of hepatic tumors. Our current perception is that LDs are complex and active structures managed by a distinct set of cellular processes. This understanding represents a significant paradigm shift from earlier perspectives. In this review, we aim to recapitulate the function of LDs within the liver, highlighting their pivotal role in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) (Hsu and Loomba, 2024) and their contribution to the progression towards more advanced pathological stages up to hepatocellular carcinoma (HC) (Farese and Walther, 2009). We are aware of the molecular complexity and changes occurring in the neoplastic evolution of the liver. Our attempt, however, is to summarize the most important and recent roles of LDs across both healthy and all pathological liver states, up to hepatocarcinoma. For more detailed insights, we direct readers to some of the many excellent reviews already available in the literature (Gluchowski et al., 2017; Hu et al., 2020; Seebacher et al., 2020; Paul et al., 2022).

Over-expression of glutathione S-transferase (GST) can promote Cisplatin resistance in hepatocellular carcinoma (HCC) treatment. Hence, inhibiting GST is an attractive strategy to improve Cisplatin sensitivity in HCC therapy. Although several synthesized GST inhibitors have been developed, the side effects and narrow spectrum for anticancer seriously limit their clinical application. Considering the abundance of natural compounds with anticancer activity, this study developed a rapid fluorescence technique to screen \"green\" natural GST inhibitors with high specificity. The fluorescence assay demonstrated that schisanlactone B (hereafter abbreviated as C1) isolated from Xue tong significantly down-regulated GST levels in Cisplatin-resistant HCC cells in vitro and in vivo. Importantly, C1 can selectively kill HCC cells from normal liver cells, effectively improving the therapeutic effect of Cisplatin on HCC mice by down-regulating GST expression. Considering the high GST levels in HCC patients, this compound demonstrated the high potential for sensitizing HCC therapy in clinical practice by down-regulating GST levels.

Liver lesions are common in oncology, and various focal treatments can be used, such as surgery, chemoembolization, radiofrequency, and systemic treatment. However, these treatments are often not feasible for a number of reasons, including the patient\'s general health or the characteristics of the lesion itself. Additionally, localized relapses may occur after focal treatments. In the past, liver radiotherapy was limited by the toxicities it caused and was mainly used in palliative situations or specific pre-transplant management. However, advancements in high-precision radiotherapy, like hypofractionated radiotherapy in stereotactic conditions, have allowed to treat the lesions with minimal margins, delivering higher doses while reducing the healthy liver\'s exposure. Increasingly, retrospective and prospective studies have demonstrated the effectiveness and safety of hypofractionation for both primary and secondary liver lesions. This review discusses the indications, results, and techniques of this type of treatment.
Les lésions hépatiques primitives ou secondaires sont une situation fréquente en oncologie. Plusieurs types de traitements focaux peuvent être appliqués : chirurgie, chimio-embolisation, radio-fréquence, traitement systémique. Néanmoins, les traitements focaux sont régulièrement contre-indiqués, soit par l’état général et les antécédents du patient, soit par la lésion en elle-même (volume, situation). De plus, il peut y avoir des patients qui présentent des rechutes localisées après ce type de prise en charge. Le foie est un organe très radiosensible, et la radiothérapie hépatique a longtemps été limitée par les toxicités qu’elle engendrait. La radiothérapie est le plus souvent utilisée dans les situations très palliatives (irradiation hépatique en totalité) ou dans certains schémas de prise en charge avant greffe. Pourtant, l’avènement de la radiothérapie de haute précision, telle que la radiothérapie hypofractionnée en condition stéréotaxique, permet de traiter les lésions avec des marges minimes et donc, d’augmenter la dose délivrée en diminuant le volume de foie sain irradié. On retrouve aujourd’hui un nombre de plus en plus important de séries rétrospectives et prospectives qui décrivent son efficacité et sa tolérance tant pour les lésions primitives que secondaires. Nous faisons ici un point sur les indications, les résultats et les modalités de ce type de traitement.

With high incidence of hepatocarcinoma and limited effective treatments, most patients suffer in pain. Antitumor drugs are single-targeted, toxicity, causing adverse side effects and resistance. Dihydroartemisinin (DHA) inhibits tumor through multiple mechanisms effectively. This study explores and evaluates safety and potential mechanism of DHA towards human hepatocarcinoma based on network pharmacology in a comprehensive way. Adsorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of DHA were evaluated with pkCSM, SwissADME, and ADMETlab. Potential targets of DHA were obtained from SwissTargetPrediction, Drugbank, TargetNET, and PharmMapper. Target gene of hepatocarcinoma was obtained from OMIM, GeneCards, and DisGeNET. Overlapping targets and hub genes were identified and analyzed for Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome pathway. Molecular docking was utilized to investigate the interactions sites and hydrogen bonds. Cell counting kit-8 (CCK8), wound healing, invasion, and migration assays on HepG2 and SNU387 cell proved DHA inhibits malignant biological features of hepatocarcinoma cell. DHA is safe and desirable for clinical application. A total of 131 overlapping targets were identified. Biofunction analysis showed targets were involved in kinase activity, protein phosphorylation, intracellular reception, signal transduction, transcriptome dysregulation, PPAR pathway, and JAK-STAT signaling axis. Top 9 hub genes were obtained using MCC (Maximal Clique Centrality) algorithm, namely CDK1, CCNA2, CCNB1, CCNB2, KIF11, CHEK1, TYMS, AURKA, and TOP2A. Molecular docking suggests that all hub genes form a stable interaction with DHA for optimal binding energy were all less than - 5 kcal/mol. Dihydroartemisinin might be a potent and safe anticarcinogen based on its biological safety and effective therapeutic effect.

The outcome of liver transplantation (LT) for hepatocarcinoma (HCC) is strongly influenced by HCC staging, which is based on radiological examinations in a pre-LT setting; concordance between pre-LT radiological and definitive pathological staging remains controversial. To address this issue, we retrospectively analyzed our LT series to assess concordance between radiology and pathology and to explore the factors associated with poor concordance and outcomes. We included all LTs with an HCC diagnosis performed between 2013 and 2018. Concordance (Co group) was defined as a comparable tumor burden in preoperative imaging and post-transplant pathology; otherwise, non-concordance was diagnosed (nCo group). Concordance between radiology and pathology was observed in 32/134 patients (Co group, 24%). The number and diameter of the nodules were higher when nCo was diagnosed, as was the number of pre-LT treatments. Although concordance did not affect survival, more than three pre-LT treatments led to a lower disease-free survival. Patients who met the Milan Criteria (Milan-in patients) were more likely to receive ≥three prior treatments, leading to a lower survival in multi-treated Milan-in patients than in other Milan-in patients. In conclusion, the concordance rate between the pre-LT imaging and histopathological results was low in patients with a high number of nodules. Multiple bridging therapies reduce the accuracy of pre-LT imaging in predicting HCC stages and negatively affect outcomes after LT.

Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is an aggressive hepatic cancer that has characteristics of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). For resectable disease, liver resection is the preferred first treatment option. As for the advanced or metastatic setting, and due to its rarity, there is still no consensus on which is the optimal systemic treatment. As such, regimens used in both HCC and CC have often been used as first-line treatment options. We report a case of a male patient in his 50s, diagnosed with a cHCC-CC with lymph node and adrenal metastasis, with an extensive portal vein tumour thrombosis, that started treatment with a multikinase inhibitor - lenvatinib.

Gastrointestinal cancers are one of the most frequent cancers and a leading cause of cancer deaths worldwide. We provide an overview of the most important practice-changing trials that were either published or presented at the international scientific meetings in 2021-2023. Highlights included reports on three phase III trials (CONCORDE/PRODIGE 26, ARTDECO, and a study by Xu et al.) that evaluated dose escalation in the definitive setting for locally advanced oesophageal cancers, as well as two phase III trials that evaluated the role of chemotherapy (neo-AEGIS) and targeted therapy (NRG/RTOG 1010) in the neoadjuvant setting for adenocarcinoma oesophageal cancers or gastroesophageal junction cancer. CheckMate 577 evaluated nivolumab in patients who had residual pathological disease after neoadjuvant chemoradiation followed by complete resection. The use of radiation therapy for borderline and locally advanced pancreatic cancer is also discussed (SMART and CONKO-007 trials). Stereotactic body radiation therapy followed by sorafenib was compared to sorafenib alone in patients with hepatocellular carcinoma in the NRG/RTOG 1112 study. New options in the management of rectal cancer are emerging such as total neoadjuvant treatment (PRODIGE 23, RAPIDO, PROSPECT), organ preservation (OPRA, OPERA), and the role of immunotherapy in patients with DNA mismatch-repair deficient/microsatellite instability. Finally, preliminary results of the ACT 4 trial that evaluated de-escalation in anal cancer are presented.

An 82-year-old man with Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL) complicated by hepatocarcinoma was presented. Remission induction therapy of hyper-CVAD with half dose reduction achieved hematological complete remission (CR), but accompanied with elevated alanine aminotransferase and hyperbilirubinemia. The patient was thought intolerable for hyper-CVAD with half dose reduction due to liver toxicity, and treatment was switched to blinatumomab. Hematological CR was sustained after nine cycles of blinatumomab without exacerbation of liver dysfunction. After five courses of blinatumomab, hepatocarcinoma was treated successfully by trans-arterial chemoembolization. Two years after the diagnosis of ALL, the patient was alive in CR status of ALL.