Análise das características associadas à dificuldade de rastreamento e diagnóstico precoce do carcinoma hepatocelular em pacientes de risco / Analysis of features associated with difficulty in screening and early diagnosing hepatocellular carcinoma in risk patients

Introdução: O carcinoma hepatocelular (CHC) é o tumor maligno primário mais comum do fígado. Através do rastreamento semestral com ultrassonografia (USG) abdominal e alfafetoproteína (AFP), em pacientes de risco, seu diagnóstico pode ser realizado de maneira precoce, quando há propostas de tratamento curativo. Entretanto, a existência de inúmeras barreiras de acesso aos exames de rastreamento do CHC impacta negativamente no prognóstico dos pacientes portadores de hepatopatias crônicas. Objetivo: O estudo teve como objetivo avaliar os determinantes que dificultam o acesso ao rastreamento e diagnóstico precoce, através da USG abdominal, em pacientes de risco para CHC ou já diagnosticados com a neoplasia. Métodos: Trata-se de um estudo descritivo e transversal, onde, para avaliar os principais fatores associados a essa dificuldade nos pacientes, foi aplicado um questionário que aborda estes fatores mais prevalentes. Resultados: Durante o período de estudo, 60 pacientes foram abordados. Em uma primeira análise, foi observado que a maioria dos pacientes era do sexo masculino (54%) e idade média de 59 anos. Da doença hepática crônica, a etiologia mais observada foi álcool (48%) seguida da infecção pelo vírus C (32%). Apesar de 42,86% dos pacientes negarem dificuldades para realização dos exames de rastreio, fatores como financeiro (12,50%) e desconhecimento da doença (10,71%) foram apontados como dificultadores. Dos pacientes com CHC, foi notado que, ao diagnóstico, 62,5% não tinha perspectiva de tratamento curativo. Discussão: Quando diagnosticado precocemente, o CHC possui opções de tratamento curativo, como o transplante hepático, com intuito secundário de garantir melhor qualidade de vida ao paciente. Entretanto, a dificuldade de acesso ao exame ou o desconhecimento da doença retardam o acompanhamento deste paciente e, consequentemente, limitando as estratégias terapêuticas. Conclusão: A ação conjunta dos diferentes níveis de atenção de saúde para solucionar os principais problemas envolvidos na dificuldade de rastreio para o CHC podem auxiliar no diagnóstico precoce do câncer e, portanto, opções de tratamento curativo ao paciente.Palavras chave: Carcinoma hepatocelular, Rastreamento, Diagnóstico precoce, Detecção precoce do câncer, Fatores de riscoABSTRACTIntroduction: Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor. Through semester screening with abdominal ultrasound (US) and alpha-fetoprotein (AFP) in high-risk patients, its diagnosis can be performed early, when there are proposals for curative treatment. However, the existence of access barriers to HCC screening tests negatively impacts the prognosis of patients with chronic liver diseases. Objectives: The study aimed to evaluate the determinants that hinder access to screening and early diagnosis, through abdominal US, in patients at risk for HCC or already diagnosed with the cancer. Methods: Descriptive and cross-sectional study where, to assess the main factors associated with this difficulty in patients, a questionnaire was designed that addresses the most prevalent factors. Results: During the study period, 60 patients were evaluated. In a first analysis, it was observed that most patients were male sex (54%) and mean age was 59 years. Of the chronic liver disease, the most observed etiology was alcohol (48%) followed by hepatitis C virus infection (32%). Although 42.86% of patients deny difficulties in performing the screening tests, factors such as financial (12.50%) and lack of knowledge about the disease (10.71%) were identified as hindering factors. Of the patients with HCC, it was noted that, at diagnosis, 62.5% had no prospect of curative treatment. Discussion: When diagnosed early, HCC has curative treatment options, such as liver transplantation, with the secondary aim of guaranteeing better quality of life for the patient. However, difficult access to the exam or lack of knowledge about the disease delay the follow-up of this patient and, consequently, limit therapeutic strategies. Conclusion: A joint action of different levels of health care to solve the main problems represented in the difficulty of screening for HCC can help in the early diagnosis of cancer and, therefore, curative treatment options for the patient.Keywords: Hepatocellular carcinoma, Screening, Early diagnosis, Early detection of cancer, Risk factors

Quercetin inhibited the proliferation and invasion of hepatoblastoma cells through facilitating SIRT6-medicated FZD4 silence

Hepatoblastoma (HB) is a malignant liver tumor that occurs during childhood. The histone deacetylase SIRT6 functions as a tumor suppressor in diverse cancers. Quercetin, as activators and antioxidants of sirtuins, exhibits remarkable anticancer activity in many tumors. However, whether quercetin ameliorates HB is still unclear. In our study, we found that SIRT6 was downregulated in HB tissues and cell lines. Overexpression of SIRT6 observably suppressed cell proliferation and invasion, promoted cell apoptosis. Mechanistically, SIRT6 suppressed frizzled 4 (FZD4) transcription by deacetylating histone H3K9. Upregulation of SIRT6 reduced the protein levels of FZD4 and H3K9ac. Additionally, quercetin treatment could enhance the expression of SIRT6, repress FZD4 level, cell viability and invasion, and promote apoptosis. Overexpression of FZD4 signally reversed quercetin-treated the promotion effect on cell apoptosis, and the inhibition effects on FZD4 expression, cell viability, invasion and Wnt/β-catenin pathway related proteins. In addition, LiCl, an agonist of Wnt/β-catenin pathway, could recover the inhibition effects of quercetin on Wnt/β-catenin pathway related proteins, cell viability and invasion, and promotion effect on cell apoptosis. In vivo mouse xenograft tumor growth assay revealed that quercetin markedly suppressed tumor growth. In conclusion, these results demonstrated that the molecular mechanism of quercetin suppressing HB cell proliferation and invasion, promoting apoptosis was to promote the deacetylation of SIRT6 on FZD4 and inhibit the activation of Wnt/β-catenin pathway.

Malignant transformation of hepatic endometriosis: a case report and literature review

Background Extrapelvic endometriosis is defined as the presence of ectopic endometrial tissue in structures outside the pelvis. Although extra-pelvic endometriosis is generally considered benign conditions, malignant potential within endometriotic foci occurs even after definitive surgery. Malignant transformation of hepatic endometriosis is extremely rare. Preoperative diagnosis of this cancer is difficult, and no guidelines on the optimal management currently exist. Here, we present a case report of malignant transformation of hepatic endometriosis and a brief literature review to highlight the current knowledge of the prevalence, clinical features, diagnosis, and management of this condition. Case presentation A 50-year-old woman with a 2-year duration of progressive right upper quadrant abdominal pain was admitted to the hospital. She underwent hysterectomy and bilateral salpingo-oophorectomy for benign conditions 4 years prior. Tumor markers demonstrated elevated carbohydrate antigen (CA)-199 112U/mL (normal range: 0–35U/mL) only. Radiological imaging suggested the presence of a 10.7 × 7.7-cm mass in the right lobe of the liver extending to the diaphragm. The intraoperative frozen sections suggested malignant tumor. Right hepatectomy with infiltrating diaphragm resection was performed. The final pathology with immunohistochemistry staining confirmed endometrioid adenocarcinoma in the liver originating from preexisting hepatic endometriosis. After the multidisciplinary team meeting, the consensus was surgery followed by adjuvant chemotherapy. To our knowledge, this is the first case of Chinese woman of a malignant liver tumor originating from endometriosis ever reported by reviewing the current English medical literature. Conclusion Though rare, extrapelvic endometriosis-associated cancers should be considered as differentiated diagnosis even after hysterectomy and bilateral salpingo-oophorectomy. This case highlights the importance of collaborative efforts across multiple disciplines for accurate diagnosis and appropriate treatment of malignant transformation of hepatic endometriosis.

Identifies Oncogene PDRG1 as a Potential Prognostic Biomarker in Hepatocellular Carcinoma: A Study Based on Bioinformatics Analysis

Background: Hepatocellular carcinoma (HCC) is globally recognized as one of the most frequently occurring primary malignant liver tumor, making the identification of HCC biomarkers critically important. Methods: The gene expression and clinicopathology analysis, GO enrichment analysis (GSEA) and immune infiltration analysis are based on data obtained from The Cancer Genome Atlas (TCGA), with additional bioinformatics analyses performed. The statistical analysis was conducted in R. The protein-protein interaction (PPI) networks was constructed and the module analysis was performed using STRING and Cytoscape. Construction and evaluation of prognostic model based on PDRG1 and tumor status used nomogram and calibration.Results: The expression of PDRG1 was significantly higher in HCC tumor tissues. High expression of PDRG1 in HCC patients was significantly correlated with poor Overall Survival and adverse clinicopathological features including advanced T stage, residual tumor, histologic grade, vascular invasion, TP53 status and AFP level. GO, GSEA revealed that PDRG1 was closely correlated with DNA repair, DNA replication and cell cycle. Spearman correlation showed high expression of PDRG1 was significantly correlated with Th2 cells level in HCC patients. Nomograms based on PDRG1 and tumor stage had good predictive performance on overall survival rates of HCC patients.Conclusions: Our study demonstrated the potential significance of PDRG1 expression in the diagnosis and prognosis of HCC and further explored the function in HCC. Further study is still needed to confirm these results. The underlying mechanism revealed by these results provides a basis for PDRG1 as a new molecular target for the prevention and treatment of HCC.

USP7 promotes hepatoblastoma progression through activation PI3K/AKT signaling pathway

BACKGROUND: Hepatoblastoma (HB) is an embryonic solid tumor and the most common primary malignant liver tumor in children. HB usually occurs in infants and children. Although treatment diversity is increasing, some patients still have very poor prognosis. Many studies have investigated USP7 inhibitors for tumors. Using database information, we found that USP7 is highly expressed in HB. METHODS: Lentivirus-mediated USP7 knockdown and overexpression was performed in HB cell lines HepG2 and Huh6. CCK8 and transwell assays were used to determine cell viability and metastasis. Flow cytometry was used to study cell cycle and apoptosis. Levels of proteins were detected using western blots. RESULTS: Downregulation of USP7 resulted in significant decrease in cell proliferation, clonal formation, and cell migration and invasion. With overexpression of USP7, cellular malignant behavior increased. Cell cycle assays showed that USP7 knockdown inhibited G1 to S phase transition in the cell cycle. Upregulation of USP7 promoted the transition. Animal experiments showed USP7 facilitated tumor growth in vivo. Western blots indicated that USP7 may affect HB tumorigenesis through the PI3K/AKT signaling pathway. Furthermore, USP7 inhibitor P5091 inhibited HB development and PI3K/AKT pathway. CONCLUSION: USP7 upregulation contributed to HB genesis and development through the PI3K/AKT signaling pathway. USP7 could be a potential target for future HB treatment.

A Novelty of Long Non-coding RNA LOXL1-AS1: Suppresses Tumor Progression and Metastasis and an Independent Favorable Prognostic Factor in Hepatocellular Carcinoma

Background: Hepatocellular Carcinoma (HCC) is the second primary causes of cancer death globally, And the sixth mostly common malignant liver tumor with poor clinical results. The long term survival of HCC patients was effected and influenced by the low rate of early diagnosis and high risk of recurrence and metastasis in post operative .Although the survival of HCC patients had improved due to improved diagnosis, In Addition Increasing amount of long non-coding RNAs (lncRNAs) have been revealed to be implicated in the carcinogenesis and progression of HCC. The potential role of Loxl1-As1 in the progression and metastasis of HCC is still not clear and needs exploring and more researching.Methods: By using a lncRNA microarray, we identified a novelty of lncRNA Loxl1-As1 .The expression of lncRNA high downregulated in metastatic HCC (Loxl1-As1) in cell lines and tissues was detected by quantitative real-time PCR (qRT-PCR) and in situ hybridization (ISH).and CCK-8, colony formation and flow cytometry were performed to investigate the role of Loxl1-As1 in HCC cell proliferation, cell cycle and apoptosis in vitro and migration were investigated in HCC cell lines bot in vitro, Western blot was used to detect the downstream of Loxl1-As1.Results: Clinically investigation,Loxl1-As1 correlated with good and favorable prognosis of HCC patients. and Loxl1-As1 was down-regulated in HCC tissues and cell lines. The ISH assay revealed that Loxl1-As1 expression was significantly decreased in 177 paraffin-embedded samples from patients with HCC compared with Non-tumor tissues (adjacent tissues )and Loxl1-as1 expression directly correlated with patient prognosis. In vitro studies indicated that Loxl1-as1 promoted HCC cells’ proliferation and clonogenicity, the expression of Loxl1-as1 suppressed the growth, migration, and metastasis of HCC cells in vitro .Conclusions: Collectively, Our findings reveal a novelty Loxl1-As1for HCC progression and these study demonstrated that Loxl1-As1, overexpressed in HCC and associated with good prognosis , and it’s an important role in the progression and metastasis of HCC. Finally we suggest that lncRNA Loxl1-As1 might be a potential biomarker and therapeutic target for HCC,

Hepatocellular Carcinoma Automatic Diagnosis within CEUS and B-Mode Ultrasound Images Using Advanced Machine Learning Methods

Hepatocellular Carcinoma (HCC) is the most common malignant liver tumor, being present in 70% of liver cancer cases. It usually evolves on the top of the cirrhotic parenchyma. The most reliable method for HCC diagnosis is the needle biopsy, which is an invasive, dangerous method. In our research, specific techniques for non-invasive, computerized HCC diagnosis are developed, by exploiting the information from ultrasound images. In this work, the possibility of performing the automatic diagnosis of HCC within B-mode ultrasound and Contrast-Enhanced Ultrasound (CEUS) images, using advanced machine learning methods based on Convolutional Neural Networks (CNN), was assessed. The recognition performance was evaluated separately on B-mode ultrasound images and on CEUS images, respectively, as well as on combined B-mode ultrasound and CEUS images. For this purpose, we considered the possibility of combining the input images directly, performing feature level fusion, then providing the resulted data at the entrances of representative CNN classifiers. In addition, several multimodal combined classifiers were experimented, resulted by the fusion, at classifier, respectively, at the decision levels of two different branches based on the same CNN architecture, as well as on different CNN architectures. Various combination methods, and also the dimensionality reduction method of Kernel Principal Component Analysis (KPCA), were involved in this process. These results were compared with those obtained on the same dataset, when employing advanced texture analysis techniques in conjunction with conventional classification methods and also with equivalent state-of-the-art approaches. An accuracy above 97% was achieved when our new methodology was applied.

Laparoscopic left hepatectomy for a patient with intrahepatic cholangiocarcinoma metastasis in the falciform ligament: a case report

Background Intrahepatic cholangiocarcinoma (ICC) is primary cancer of the liver with poor prognosis because of its high potential for recurrence and metastasis. We experienced a rare case of ICC with hematogenous metastasis to the falciform ligament. We aimed to clarify the route of metastasis to the mesentery by increasing the accuracy of preoperative imaging and establish a hepatectomy to control cancer. Case presentation An 85-year-old woman was referred to our hospital for a detailed study of progressively increasing liver tumors. She had no subjective symptoms. Her medical history showed hypertension, aneurysm clipping for cerebral hemorrhage, and gallstones. A detailed physical examination and laboratory data evaluation included tumor markers but did not demonstrate any abnormalities. On computed tomography scan, contrast-enhanced ultrasound, and magnetic resonance imaging with gadolinium ethoxybenzyl diethylenetriamine penta-acetic acid, the tumor appeared to be located in liver segment IV, protruding outside the liver. It appeared to contain two distinct components; we suspected ICC in the intrahepatic tumor component. Laparoscopic observation revealed that the extrahepatic lesion was an intra-falciform ligament mass; laparoscopic left hepatectomy was performed. Microscopically, the main tumor in segment IV was 15 mm in diameter and was diagnosed as moderately and poorly differentiated ICC. The tumor of the intra-falciform ligament was not continuous with the main intrahepatic nodule and was also diagnosed as ICC with extensive necrosis. There were no infiltrates in the round ligament of the liver, and several tumor thrombi were found in the small veins of the falciform ligament. Conclusions To date, there have been a few reports of metastases of primary liver cancer to the falciform ligament. At the time of preoperative imaging and pathological diagnosis, this case was suggestive of considering that the malignant liver tumor might be suspected of metastasizing to the falciform ligament. Our case improves awareness of this pathology, which can be useful in the future when encountered by hepatic specialists and surgeons.

Laparoscopic hepatectomy for hepatic angiomyolipoma with preoperative diagnosis of other malignancy: a report of 2 cases

Background Hepatic angiomyolipoma (HAML) is a rare liver tumor, and hepatectomy is the only effective treatment. Due to the difficulty of correct diagnosis of HAML before surgery by image studies, more than 36.6% of reported HAMLs are misdiagnosed as other malignant liver tumors before surgery. As there are only few reported cases in which HAMLs were removed using laparoscopic hepatectomy, the effectiveness of laparoscopic hepatectomy for such HAMLs in which are diagnosed as other malignant liver tumor before surgery has not been reported. Case presentation Case 1: a 58-year-old female with a history of treatment for autoimmune hepatitis was preoperatively diagnosed with hepatocellular carcinoma (size: 20 mm) in segment 7 (S7) of the liver. The tumor was removed by laparoscopic partial resection and was diagnosed as a HAML through a pathological examination. The patient’s postoperative course was good, and she was recurrence-free at 37 months after the hepatectomy. Case 2: a 29-year-old female with a history of surgery for a right mature cystic teratoma was referred to our department to receive treatment for a growing 20-mm liver tumor with some calcification, which arose in S3 of the liver. A metastatic liver tumor derived from the mature cystic teratoma was suspected, and laparoscopic left lateral sectionectomy was performed. The liver tumor was diagnosed as a HAML after a pathological examination. The patient’s postoperative course was unremarkable, and more than 54 months have passed since the hepatectomy without any recurrence. Conclusions Two cases in which HAMLs were preoperatively diagnosed as other malignant liver tumor were successfully removed by laparoscopic hepatectomy with a correct postoperative diagnosis. Laparoscopic hepatectomy for the present 2 cases of HAML seemed to be effective for providing a correct diagnosis after the curative removement of liver tumor with a smaller invasion compared to open hepatectomy, and for denying risk of dissemination of the malignant tumor by needle biopsy that had to be considered before ruling out malignant tumor.

GFI1-Mediated Upregulation of LINC00675 as a ceRNA Restrains Hepatocellular Carcinoma Metastasis by Sponging miR-942-5p

Hepatocellular carcinoma (HCC) is a common malignant liver tumor worldwide. Tumor recurrence and metastasis contribute to the bad clinical outcome of HCC patients. Substantial studies have displayed lncRNAs modulate various tumorigenic processes of many cancers. Our current work was aimed to investigate the function of LINC00675 in HCC and to recognize the potential interactions between lncRNAs and microRNAs. GFI1 can exhibit a significant role in the progression of human malignant tumors. Firstly, GFI1 was identified using real-time PCR in HCC tissues and cells. In this work, we indicated GFI1 was remarkably reduced in HCC tissues and cells. Meanwhile, GFI1 specifically interacted with the promoter of LINC00675. Up-regulation of LINC00675 obviously repressed the migration and invasion capacity of SMCC-7721 and QGY-7703 cells in vitro. Moreover, decrease of LINC00675 competitively bound to miR-942-5p that contributed to the miRNA-mediated degradation of GFI1, thus facilitated HCC metastasis. The ceRNA function of LINC00675 in HCC cells was assessed and confirmed using RNA immunoprecipitation assay and RNA pull-down assays in our work. Additionally, we proved overexpression of miR-942-5p promoted HCC progression, which was reversed by the up-regulation of GFI1. In summary, LINC00675 might act as a prognostic marker for HCC, which can inhibit HCC development via regulating miR-942-5p and GFI1.