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Revista Do Colegio Brasileiro de... 2023hepatocellular adenoma - AHC - is a rare benign neoplasm of the liver more prevalent in women at reproductive age and its main complication is hemorrhage. In the...
INTRODUCTION
hepatocellular adenoma - AHC - is a rare benign neoplasm of the liver more prevalent in women at reproductive age and its main complication is hemorrhage. In the literature, case series addressing this complication are limited.
METHODS
between 2010 and 2022, 12 cases of bleeding AHC were attended in a high-complexity university hospital in southern Brazil, whose medical records were retrospectively evaluated.
RESULTS
all patients were female, with a mean age of 32 years and a BMI of 33kg/m2. The use of oral contraceptives was identified in half of the sample and also half of the patients had a single lesion. The mean diameter of the largest lesion was 9.60cm and the largest lesion was responsible for bleeding in all cases. The presence of hemoperitoneum was documented in 33% of the patients and their age was significantly higher than the patients who did not have hemoperitoneum - 38 vs 30 years, respectively. Surgical resection of the bleeding lesion was performed in 50% of the patients and the median number of days between bleeding and resection was 27 days. In only one case, embolization was used. The relation between ingrowth of the lesions and the time, in months, was not obtained in this study.
CONCLUSION
it is concluded that the bleeding AHC of the present series shows epidemiological agreement with the literature and may suggest that older patients trend to have hemoperitoneum more frequently, a fact that should be investigated in further studies.
Topics: Humans; Female; Adult; Male; Adenoma, Liver Cell; Liver Neoplasms; Carcinoma, Hepatocellular; Hemoperitoneum; Retrospective Studies
PubMed: 37436285
DOI: 10.1590/0100-6991e-20233549-en -
Anticancer Research Oct 2023It has been reported that patients with macroscopic vascular invasion accompanying hepatocellular carcinoma have a poor prognosis. Modern molecular therapy with... (Review)
Review
It has been reported that patients with macroscopic vascular invasion accompanying hepatocellular carcinoma have a poor prognosis. Modern molecular therapy with multitargeted tyrosine kinase inhibitors and immune checkpoint inhibitors has shown promising results in patients with metastatic hepatocellular carcinoma; however, molecular therapy is limited to patients with Child-Pugh class A disease. This review summarizes the present status of surgical therapies, including conversion hepatectomy, for patients with MVI in the developing era of novel molecular therapy. Phase III studies showed patients with macroscopic vascular invasion had significant survival benefits from sorafenib [hazard ratio (HR)=0.68] and regorafenib (HR=0.67) versus placebo, and nivolumab (HR=0.74) versus sorafenib. Lenvatinib and atezolizumab plus bevacizumab showed marginal effects. It is currently widely assumed that molecular therapy alone will not cure the disease but that additional conversion hepatectomy will be required. A response other than progressive disease is essential but a pathological complete response is not always required. A significant randomized controlled trial has already started in China to assess the necessity for conversion hepatectomy after effective atezolizumab plus bevacizumab treatment, and the results are still awaited. According to Japanese national data, upfront hepatectomy can be recommended for patients with initially resectable disease and macroscopic vascular invasion other than for those with tumors in the main portal vein and the inferior vena cava. In addition, adequate adjuvant therapies with hepatic arterial chemotherapy and transarterial chemoembolization may be beneficial but an effective adjuvant molecular therapy is currently unavailable. In conclusion, novel molecular therapies with higher response rates customized to the oncologic characteristics of each hepatocellular carcinoma with macroscopic vascular invasion are needed to increase the likelihood of conversion surgery and improve long-term outcomes.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Sorafenib; Bevacizumab; Treatment Outcome; Chemoembolization, Therapeutic; Neoplasm Invasiveness; Randomized Controlled Trials as Topic
PubMed: 37772548
DOI: 10.21873/anticanres.16623 -
Translational Research : the Journal of... Sep 2024Hepatocellular carcinoma (HCC) is among the most fatal types of malignancy, with a high prevalence of relapse and limited treatment options. As a critical regulator of...
Hepatocellular carcinoma (HCC) is among the most fatal types of malignancy, with a high prevalence of relapse and limited treatment options. As a critical regulator of ferroptosis and redox homeostasis, glutathione peroxidase 4 (GPX4) is commonly upregulated in HCC and is hypothesized to facilitate cancer metastasis, but this has not been fully explored in HCC. Here, we report that up-regulated GPX4 expression in HCC is strongly associated with tumor metastasis. FACS-based in vivo and in vitro analysis revealed that a cell subpopulation featuring lower cellular reactive oxygen species levels and ferroptosis resistance were involved in GPX4-mediated HCC metastasis. Mechanistically, GPX4 overexpressed in HCC tumor cells was enriched in the nucleus and transcriptionally silenced GRHL3 expression, thereby activating PTEN/PI3K/AKT signaling and promoting HCC metastasis. Functional studies demonstrated that GPX4 amino acids 110-145 are a binding site that interacts with the GRHL3 promoter. As AKT is a downstream target of GPX4, we combined the AKT inhibitor, AKT-IN3, with lenvatinib to effectively inhibit HCC tumor cell metastasis. Overall, these results indicate that the GPX4/GRHL3/PTEN/PI3K/AKT axis controls HCC cell metastasis and lenvatinib combined with AKT-IN3 represents a potential therapeutic strategy for patients with metastatic HCC.
Topics: Humans; Liver Neoplasms; PTEN Phosphohydrolase; Phospholipid Hydroperoxide Glutathione Peroxidase; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Animals; Transcription Factors; Neoplasm Metastasis; Cell Line, Tumor; DNA-Binding Proteins; Carcinoma, Hepatocellular; Signal Transduction; Mice; Gene Expression Regulation, Neoplastic; Male; Mice, Nude; Transcription, Genetic
PubMed: 38797432
DOI: 10.1016/j.trsl.2024.05.007 -
Genome Medicine Nov 2023Early detection of hepatocellular carcinoma (HCC) is important in order to improve patient prognosis and survival rate. Methylation sequencing combined with neural...
BACKGROUND
Early detection of hepatocellular carcinoma (HCC) is important in order to improve patient prognosis and survival rate. Methylation sequencing combined with neural networks to identify cell-free DNA (cfDNA) carrying aberrant methylation offers an appealing and non-invasive approach for HCC detection. However, some limitations exist in traditional methylation detection technologies and models, which may impede their performance in the read-level detection of HCC.
METHODS
We developed a low DNA damage and high-fidelity methylation detection method called No End-repair Enzymatic Methyl-seq (NEEM-seq). We further developed a read-level neural detection model called DeepTrace that can better identify HCC-derived sequencing reads through a pre-trained and fine-tuned neural network. After pre-training on 11 million reads from NEEM-seq, DeepTrace was fine-tuned using 1.2 million HCC-derived reads from tumor tissue DNA after noise reduction, and 2.7 million non-tumor reads from non-tumor cfDNA. We validated the model using data from 130 individuals with cfDNA whole-genome NEEM-seq at around 1.6X depth.
RESULTS
NEEM-seq overcomes the drawbacks of traditional enzymatic methylation sequencing methods by avoiding the introduction of unmethylation errors in cfDNA. DeepTrace outperformed other models in identifying HCC-derived reads and detecting HCC individuals. Based on the whole-genome NEEM-seq data of cfDNA, our model showed high accuracy of 96.2%, sensitivity of 93.6%, and specificity of 98.5% in the validation cohort consisting of 62 HCC patients, 48 liver disease patients, and 20 healthy individuals. In the early stage of HCC (BCLC 0/A and TNM I), the sensitivity of DeepTrace was 89.6 and 89.5% respectively, outperforming Alpha Fetoprotein (AFP) which showed much lower sensitivity in both BCLC 0/A (50.5%) and TNM I (44.7%).
CONCLUSIONS
By combining high-fidelity methylation data from NEEM-seq with the DeepTrace model, our method has great potential for HCC early detection with high sensitivity and specificity, making it potentially suitable for clinical applications. DeepTrace: https://github.com/Bamrock/DeepTrace.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Cell-Free Nucleic Acids; Biomarkers, Tumor; DNA, Neoplasm; DNA Methylation; Neural Networks, Computer
PubMed: 37936230
DOI: 10.1186/s13073-023-01238-8 -
Drug Resistance Updates : Reviews and... May 2024Hepatocellular carcinoma (HCC) is the most common digestive malignancyin the world, which is frequently diagnosed at late stage with a poor prognosis. For most patients... (Review)
Review
Hepatocellular carcinoma (HCC) is the most common digestive malignancyin the world, which is frequently diagnosed at late stage with a poor prognosis. For most patients with advanced HCC, the therapeutic options arelimiteddue to cancer occurrence of drug resistance. Hepatic cancer stem cells (CSCs) account for a small subset of tumor cells with the ability of self-renewal and differentiationin HCC. It is widely recognized that the presence of CSCs contributes to primary and acquired drug resistance. Therefore, hepatic CSCs-targeted therapy is considered as a promising strategy to overcome drug resistance and improve therapeutic outcome in HCC. In this article, we review drug resistance in HCC and provide a summary of potential targets for CSCs-based therapy. In addition, the development of CSCs-targeted therapeuticsagainst drug resistance in HCC is summarized in both preclinical and clinical trials. The in-depth understanding of CSCs-related drug resistance in HCC will favor optimization of the current therapeutic strategies and gain encouraging therapeutic outcomes.
Topics: Humans; Carcinoma, Hepatocellular; Neoplastic Stem Cells; Liver Neoplasms; Drug Resistance, Neoplasm; Antineoplastic Agents; Animals; Molecular Targeted Therapy
PubMed: 38640592
DOI: 10.1016/j.drup.2024.101084 -
International Immunopharmacology Nov 2023Liver transplantation is one of the most effective treatments for hepatocellular carcinoma (HCC). The balance between inhibiting immune rejection and preventing tumor...
Liver transplantation is one of the most effective treatments for hepatocellular carcinoma (HCC). The balance between inhibiting immune rejection and preventing tumor recurrence after liver transplantation is the key to determining the long-term prognosis of patients with HCC after liver transplantation. In our previous study, we found that capecitabine (CAP), an effective drug for the treatment of HCC, could exert an immunosuppressive effect after liver transplantation by inducing T cell ferroptosis. Recent studies have shown that ferroptosis is highly associated with autophagy. In this study, we confirmed that the autophagy inducer rapamycin (RAPA) combined with metronomic capecitabine (mCAP) inhibits glutathione peroxidase 4 (GPX4) and promotes ferroptosis in CD4 T cells to exert immunosuppressive effects after rat liver transplantation. Compared with RAPA or mCAP alone, the combination of RAPA and mCAP could adequately reduce liver injury in rats with acute rejection after transplantation. The CD4 T cell counts in peripheral blood, spleen, and transplanted liver of recipient rats significantly decreased, and the oxidative stress level and ferrous ion concentration of CD4 T cells significantly increased in the combination group. In vitro, the combination of drugs significantly promoted autophagy, decreased GPX4 protein expression, and induced ferroptosis in CD4 T cells. In conclusion, the autophagy inducer RAPA improved the mCAP-induced ferroptosis in CD4 T cells. Our results support the concept of ferroptosis as an autophagy-dependent cell death and suggest that the combination of ferroptosis inducers and autophagy inducers is a new research direction for improving immunosuppressive regimens after liver transplantation.
Topics: Humans; Rats; Animals; Sirolimus; T-Lymphocytes; Capecitabine; Liver Transplantation; Ferroptosis; Carcinoma, Hepatocellular; Liver Neoplasms; Neoplasm Recurrence, Local; CD4-Positive T-Lymphocytes
PubMed: 37625370
DOI: 10.1016/j.intimp.2023.110810 -
Journal of Gastrointestinal Surgery :... Oct 2023The latest developments in cancer immunotherapy, namely the introduction of immune checkpoint inhibitors, have led to a fundamental change in advanced cancer treatments.... (Review)
Review
The latest developments in cancer immunotherapy, namely the introduction of immune checkpoint inhibitors, have led to a fundamental change in advanced cancer treatments. Imaging is crucial to identify tumor response accurately and delineate prognosis in immunotherapy-treated patients. Simultaneously, advances in image acquisition techniques, notably functional and molecular imaging, have facilitated more accurate pretreatment evaluation, assessment of response to therapy, and monitoring for tumor recurrence. Traditional approaches to assessing tumor progression, such as RECIST, rely on changes in tumor size, while new strategies for evaluating tumor response to therapy, such as the mRECIST and the EASL, rely on tumor enhancement. Moreover, the assessment of tumor volume, enhancement, cellularity, and perfusion are some novel techniques that have been investigated. Validation of these novel approaches should rely on comparing their results with those of standard evaluation methods (EASL, mRECIST) while considering the ultimate outcome, which is patient survival. More recently, immunotherapy has been used in the management of primary liver tumors. However, little is known about its efficacy. This article reviews imaging modalities and techniques for assessing tumor response and survival in immunotherapy-treated patients with primary hepatic malignancies.
Topics: Humans; Carcinoma, Hepatocellular; Treatment Outcome; Neoplasm Recurrence, Local; Liver Neoplasms
PubMed: 37464140
DOI: 10.1007/s11605-023-05762-1 -
Chinese Medical Journal Jun 2024In humans, the liver is a central metabolic organ with a complex and unique histological microenvironment. Hepatocellular carcinoma (HCC), which is a highly aggressive... (Review)
Review
In humans, the liver is a central metabolic organ with a complex and unique histological microenvironment. Hepatocellular carcinoma (HCC), which is a highly aggressive disease with a poor prognosis, accounts for most cases of primary liver cancer. As an emerging hallmark of cancers, metabolic reprogramming acts as a runaway mechanism that disrupts homeostasis of the affected organs, including the liver. Specifically, rewiring of the liver metabolic microenvironment, including lipid metabolism, is driven by HCC cells, propelling the phenotypes of HCC cells, including dissemination, invasion, and even metastasis in return. The resulting formation of this vicious loop facilitates various malignant behaviors of HCC further. However, few articles have comprehensively summarized lipid reprogramming in HCC metastasis. Here, we have reviewed the general situation of the liver microenvironment and the physiological lipid metabolism in the liver, and highlighted the effects of different aspects of lipid metabolism on HCC metastasis to explore the underlying mechanisms. In addition, we have recapitulated promising therapeutic strategies targeting lipid metabolism and the effects of lipid metabolic reprogramming on the efficacy of HCC systematical therapy, aiming to offer new perspectives for targeted therapy.
Topics: Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Lipid Metabolism; Tumor Microenvironment; Neoplasm Metastasis
PubMed: 38738689
DOI: 10.1097/CM9.0000000000003144 -
Medicina 2024Ewing sarcoma (ES) and primitive neuroectodermal tumor (PNET) belong to the group of neoplasms called small round cell tumors. PNETs have been divided into central and...
Ewing sarcoma (ES) and primitive neuroectodermal tumor (PNET) belong to the group of neoplasms called small round cell tumors. PNETs have been divided into central and peripheral. ES and peripheral PNETs arise from bones, soft tissues, or peripheral nerves. We present a case of hepatic ES/PNET in a healthy man that began four months before consultation with abdominal symptoms and weight loss. Upper gastrointestinal endoscopy and laboratory tests revealed no notable findings. The abdominal tomography revealed an enlarged liver due to a solid lesion that involved all its segments with intravenous contrast enhancement and large areas of necrosis. It compressed and displaced neighboring structures. Core needle biopsy of the liver lesion was performed: small round cell neoplasm. Immunohistochemistry revealed negativity for CD45, CKA1/A3, chromogranin, synaptophysin, and cytokeratins CK7 and CK20. Dim CD56 expression and CD99, FLI-1, and NKX2 positivity. He underwent chemotherapy treatment with carboplatin and etoposide for 6 cycles with clinical improvement and tolerance. Control images showed reduction of the mass with involvement of the right hepatic lobe, involvement of the inferior vena cava, infiltration of the right adrenal gland and upper pole of the right kidney. He was referred to hepatobiliary surgery for surgical resection of the residual lesion. The patient rejected the proposed surgical procedure. Our objective is to highlight the clinical and histological diagnostic challenge of this entity that requires ruling out other clinical entities.
Topics: Humans; Male; Liver Neoplasms; Sarcoma, Ewing; Tomography, X-Ray Computed; Immunohistochemistry; Adult; Neuroectodermal Tumors, Primitive, Peripheral
PubMed: 38907976
DOI: No ID Found -
Cancer Medicine Oct 2023Liver-resident natural killer (lr-NK) cells are distinct from conventional NK cells and exhibit higher cytotoxicity against hepatoma via tumor necrosis factor-related...
BACKGROUND
Liver-resident natural killer (lr-NK) cells are distinct from conventional NK cells and exhibit higher cytotoxicity against hepatoma via tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). However, the mechanism by which partial hepatectomy (PH) significantly suppresses TRAIL expression in lr-NK cells remains unclear.
METHODS
This study aimed to investigate the PH influence on the function and characteristics of liver-resident NK (lr-NK) cells using a PH mouse model.
RESULTS
Here, we report that PH alters the differentiation pattern of NK cells in the liver, and an aryl hydrocarbon receptor (AhR) molecule is involved in these changes. Treatment with the AhR agonist 6-formylindolo[3,2-b]carbazole (FICZ) inhibited the maturation of NK cells. FICZ increased the immature subtype proportion of NK cells with high TRAIL activity and decreased the mature subtype of NK cells with low TRAIL activity. Consequently, FICZ increased the expression of TRAIL and cytotoxic activity of NK cells in the liver, and this effect was confirmed even after hepatectomy. The participation of AhR promoted FoxO1 expression in the mTOR signaling pathway involved in the maturation of NK cells, resulting in TRAIL expression.
CONCLUSION
Our findings provide direct in-vivo evidence that partial hepatectomy affects lrNK cell activity through NK cell differentiation in the liver. Perioperative therapies using an AhR agonist to improve NK cell function may reduce the recurrence of hepatocellular carcinoma after hepatectomy.
Topics: Animals; Mice; Carcinoma, Hepatocellular; Hepatectomy; Killer Cells, Natural; Mice, Inbred C57BL; Receptors, Aryl Hydrocarbon; TNF-Related Apoptosis-Inducing Ligand; Tumor Necrosis Factor-alpha; Liver Neoplasms; Neoplasm Recurrence, Local
PubMed: 37747052
DOI: 10.1002/cam4.6554