Metastatic lung tumor from hepatocellular carcinoma with tumor thrombus invasion in the pulmonary vein: a case report.

BACKGROUND: Metastatic lung tumor with a tumor thrombus in the peripheral pulmonary vein is very rare. We present a case of a metastatic lung tumor from hepatocellular carcinoma (HCC) with tumor thrombus invasion in the pulmonary vein that was diagnosed preoperatively and underwent complete resection by segmentectomy. CASE PRESENTATION: A 77-year-old man underwent laparoscopic lateral segment hepatectomy for HCC eight years ago. Protein induced by vitamin K absence or antagonist-II remained elevated from two years ago. Contrast-enhanced chest computed-tomography (CT) showed a 27 mm nodule in the right apical segment (S1). He was pathologically diagnosed with a metastatic lung tumor from HCC via transbronchoscopic biopsy. We planned to perform right S1 segmentectomy. Before surgery, contrast-enhanced CT in the pulmonary vessels phase for three-dimensional reconstruction showed that the tumor extended into the adjusting peripheral pulmonary vein, and we diagnosed tumor thrombus invasion in V1a. The surgery was conducted under 3-port video-assisted thoracic surgery. First, V1 was ligated and cut. A1 and B1 were cut. The intersegmental plane was cut with mechanical staplers. Pathological examination revealed moderately-differentiated metastatic HCC with tumor thrombus invasions in many pulmonary veins, including V1a. No additional postoperative treatments were performed. CONCLUSIONS: As malignant tumors tend to develop a tumor thrombus in the primary tumor, it might be necessary to perform contrast-enhanced CT in the pulmonary vessel phase to check for a tumor thrombus before the operation for metastatic lung tumors.

Repeated surgery for hemorrhagic brain metastases from hepatocellular carcinoma: palliation or effective part of a multimodal treatment? A case-based approach.

Brain metastases from hepatocellular carcinoma (HCCBM) are encountered very rarely in clinical practice, especially in western countries. Only a minority of patients undergoes resective surgery, as clinical picture is usually complex and presentation is often catastrophic with intra-cerebral hemorrhage (ICH). Neurosurgical intervention can be not only life-saving but may also alleviate significantly the burden of symptoms. We present the case of a patient with six metachronous hemorrhagic HCCBM in which emergent surgery extended survival by 9 months, of which seven spent in near-normal life quality, stressing the role of neurosurgery in the evaluation of HCCBM patients.

LncRNA CEBPA-DT promotes liver cancer metastasis through DDR2/ß-catenin activation via interacting with hnRNPC.

BACKGROUND: Hepatocellular carcinoma (HCC) is the world's third leading cause of cancer-related death; due to the fast growth and high prevalence of tumor recurrence, the prognosis of HCC patients remains dismal. Long non-coding RNA CEBPA-DT, a divergent transcript of the CCAAT Enhancer Binding Protein Alpha (CEBPA) gene, has been shown to participate in multiple tumor progression. However, no research has established its cancer-promoting mechanism in HCC yet. METHODS: CEBPA-DT was identified in human HCC tissues through RNA sequencing. The expression level of CEBPA-DT was assessed by quantitative real-time PCR. The biological effects of CEBPA-DT were evaluated in vitro and in vivo through gain or loss of function experiments. RNA fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP) and RNA pull-down assays were applied to investigate the downstream target of CEBPA-DT. Immunofluorescence, subcellular protein fractionation, western blot, and co-immunoprecipitation were performed to analyze the subcellular location of ß-catenin and its interaction with Discoidin domain-containing receptor 2 (DDR2). RESULTS: CEBPA-DT was upregulated in human HCC tissues with postoperative distant metastasis and intimately related to the worse prognosis of HCC patients. Silencing of CEBPA-DT inhibited the growth, migration and invasion of hepatoma cells in vitro and in vivo, while enhancement of CEBPA-DT played a contrasting role. Mechanistic investigations demonstrated that CEBPA-DT could bind to heterogeneous nuclear ribonucleoprotein C (hnRNPC), which facilitated cytoplasmic translocation of hnRNPC, enhanced the interaction between hnRNPC and DDR2 mRNA, subsequently promoted the expression of DDR2. Meanwhile, CEBPA-DT induced epithelial-mesenchymal transition (EMT) process through upregulation of Snail1 via facilitating nuclear translocation of ß-catenin. Using DDR2 inhibitor, we revealed that the CEBPA-DT induced the interaction between DDR2 and ß-catenin, thus promoting the nuclear translocation of ß-catenin to activate transcription of Snail1, contributing to EMT and HCC metastasis. CONCLUSIONS: Our results suggested that CEBPA-DT promoted HCC metastasis through DDR2/ß-catenin mediated activation of Snail1 via interaction with hnRNPC, indicating that the CEBPA-DT-hnRNPC-DDR2/ß-catenin axis may be used as a potential therapeutic target for HCC treatment.

Short-term prognosis for hepatocellular carcinoma patients with lung metastasis: A retrospective cohort study based on the SEER database.

Our study aimed to develop a prediction model to predict the short-term mortality of hepatocellular carcinoma (HCC) patients with lung metastasis. The retrospective data of HCC patients with lung metastasis was from the Surveillance, Epidemiology, and End Results registration database between 2010 and 2015. 1905 patients were randomly divided into training set (n = 1333) and validation set (n = 572). There were 1092 patients extracted from the Surveillance, Epidemiology, and End Results database 2015 to 2019 as the validation set. The variable importance was calculated to screen predictors. The constructed prediction models of logistic regression, random forest, broad learning system, deep neural network, support vector machine, and naïve Bayes were compared through the predictive performance. The mortality of HCC patients with lung metastasis was 51.65% within 1 month. The screened prognostic factors (age, N stage, T stage, tumor size, surgery, grade, radiation, and chemotherapy) and gender were used to construct prediction models. The area under curve (0.853 vs. 0.771) of random forest model was more optimized than that of logistic regression model in the training set. But, there were no significant differences in testing and validation sets between random forest and logistic regression models. The value of area under curve in the logistic regression model was significantly higher than that of the broad learning system model (0.763 vs. 0.745), support vector machine model (0.763 vs. 0.689) in the validation set, and higher than that of the naïve Bayes model (0.775 vs. 0.744) in the testing model. We further chose the logistic regression prediction model and built the prognostic nomogram. We have developed a prediction model for predicting short-term mortality with 9 easily acquired predictors of HCC patients with lung metastasis, which performed well in the internal and external validation. It could assist clinicians to adjust treatment strategies in time to improve the prognosis.

A Rare Case of Metastatic Hepatocellular Carcinoma to the Hard Palate.

Extrahepatic metastasis of hepatocellular carcinoma (HCC) to the head and neck is unusual, especially the oral cavity/maxillofacial region. Metastatic HCC to the hard palate, however, is particularly rare. The most common site of HCC metastasis is the lung, followed by lymph nodes, bone, and adrenal gland. Importantly, oral cavity metastatic HCC may be misdiagnosed as a primary malignancy, such as a salivary gland carcinoma. In this article, we describe a young woman with metastatic HCC to the hard palate that was initially diagnosed as an acinic cell carcinoma.

Hemorrhagic Brain Metastasis as an Initial Presentation of Hepatocellular Carcinoma in a Patient With Alcohol-Related Liver Cirrhosis: A Case Report and Review of Literature.

Hepatocellular carcinoma (HCC) is the most common primary hepatic cancer. Although it usually presents as a liver mass, rarely HCC can have an initial presentation at an extrahepatic site before the diagnosis of the primary lesion in the liver. Even rarely was that brain metastasis as initial extrahepatic presentations. Furthermore, the initial presentation of HCC as brain metastases has been with most cases being secondary to hepatitis-related hepatoma. In this case report, we are presenting a rare and unusual case of hemorrhagic cerebral metastasis as an initial extrahepatic presentation of an alcohol-related hepatoma. Our case is the second case in the English literature that has been presented in such a way. Due to the uncommonness of presentation, there can be diagnostic dilemmas and delay in treatment. Therefore, a high level of suspicion is needed in the high-risk patients of HCC who present with unexplained or new neurological signs and symptoms. More exploration is warranted for clinical research and treatment guidelines for brain metastases of HCC to help improve survival and quality of life.

AGA Clinical Practice Guideline on Systemic Therapy for Hepatocellular Carcinoma.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC), the most common primary liver cancer, remains a deadly cancer, with an incidence that has tripled in the United States since 1980. In recent years, new systemic therapies for HCC have been approved and a critical assessment of the existing data is necessary to balance benefits and harms and inform the development of evidence-based guidelines. METHODS: The American Gastroenterological Association formed a multidisciplinary group consisting of a Technical Review Panel and a Guideline Panel. The Technical Review Panel prioritized clinical questions and outcomes according to their importance for clinicians and patients and conducted an evidence review of systemic therapies in patients with advanced-stage HCC. The Grading of Recommendations Assessment, Development and Evaluation framework was used to assess evidence. The Guideline Panel reviewed the evidence and used the Evidence-to-Decision Framework to develop recommendations. RESULTS: The Panel reviewed the evidence, summarized in the Technical Review, for the following medications approved by the US Food and Drug Administration for HCC: first-line therapies: bevacizumab+atezolizumab, sorafenib, and lenvatinib; second-line therapies: cabozantinib, pembrolizumab, ramucirumab, and regorafenib; and other agents: bevacizumab, nivolumab, and nivolumab+ipilimumab. CONCLUSIONS: The Panel agreed on 11 recommendations focused on systemic therapy for HCC in patients who are not eligible for locoregional therapy or resection, those with metastatic disease and preserved liver function, those with poor liver function, and those on systemic therapy as adjuvant therapy.

LncRNA THEMIS2-211, a tumor-originated circulating exosomal biomarker, promotes the growth and metastasis of hepatocellular carcinoma by functioning as a competing endogenous RNA.

Hepatocellular carcinoma (HCC) is a major challenge for human health. Finding reliable diagnostic biomarkers and therapeutic targets for HCC is highly desired in the clinic. Currently, circulating exosomal lncRNA is a promising biomarker for the diagnosis of cancer and lncRNA is also a potential target in cancer therapy. Here, the diagnostic value of a panel based on exosomal lncRNA THEMIS2-211 and PRKACA-202, superior to that of AFP, was identified for diagnosing human HCC. Besides, the performance of exosomal lncRNA THEMIS2-211 alone exceeds that of AFP in diagnosing early-stage HCC patients (stage I). Furthermore, lncRNA THEMIS2-211 is highly expressed in HCC tissues and correlated with the poor prognosis of HCC patients. LncRNA THEMIS2-211 is upregulated and localized in the cytoplasm of HCC cells. LncRNA THEMIS2-211 exerts its biological function as an oncogene that promotes the proliferation, migration, invasion, EMT of HCC cells by physically interacting with miR-940 and therefore promoting SPOCK1 expressions. Rescue assays show the regulation of SPOCK1 by lncRNA THEMIS2-211 dependents on miR-940. The discovery of lncRNA THEMIS2-211 further illuminates the molecular pathogenesis of HCC and the THEMIS2-211/miR-940/SPOCK1 axis may act as a potential therapeutic target for HCC.

Objective to identify and verify the regulatory mechanism of DTNBP1 as a prognostic marker for hepatocellular carcinoma.

Although the overall survival of hepatocellular carcinoma (HCC) patients has been significantly improved, prognostic clinical evaluation remains a substantial problem owing to the heterogeneity and complexity of tumor. A reliable and accurate predictive biomarker may assist physicians in better monitoring of patient treatment outcomes and follow the overall survival of patients. Accumulating evidence has revealed that DTNBP1 plays functional roles in cancer prognosis. Therefore, the expression and function of DTNBP1in HCC was systematically investigated in our study. The expression and prognostic value of DTNBP1 were investigated using the data from Cancer Genome Atlas (TCGA) database, Gene Expression Omnibus (GEO) cohorts and clinical samples. A series of cellular function assays were performed to elucidate the effect of DTNBP1 on cellular proliferation, apoptosis and metastasis. Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment and Protein-protein interaction (PPI) network construction were performed to screen the genes with highest interaction scores with DTNBP1. Finally, the underlying mechanism was also analyzed using Gene Set Enrichment Analysis (GSEA) and confirmed using RT-qPCR and western blotting. DTNBP1 was upregulated in many types of cancers, especially in HCC. The DTNBP1 expression levels is associated with clinicopathologic variables and patient survival status. The differential expression of DTNBP1 could be used to determine the risk stratification of patients with HCC. DTNBP1 deficiency inhibited cell proliferation and metastasis, but promoted cell apoptosis. Mechanistically, DTNBP1 regulated the cell cycle progression through affecting the expression of cell cycle-related genes such as CDC25A, CCNE1, CDK2, CDC20, CDC25B, CCNB1, and CDK1. DTNBP1, which regulates the cell cycle progression, may be used as a prognostic marker for HCC.

Electrochemotherapy for the palliative management of non-skin-origin head and neck cancer: case series and UK national survey.

OBJECTIVES: Electrochemotherapy uses electric fields to facilitate the influx of chemotherapy into cancer cells, producing a targeted effect. For head and neck cancer, it is mainly used for palliation of non-skin-origin metastases. It is used infrequently in the UK. This paper presents our experience and a UK survey to identify its frequency of use. METHODS: Between 2016 and 2019, a prospective database was created and reviewed. Only patients with non-skin-origin metastatic head and neck cancer, with no other palliative options, were included. Survival length, complications and symptomatic benefit were assessed. The survey was conducted via e-mail. RESULTS: Five patients were included: three with squamous cell carcinoma, one with esthesioneuroblastoma and one with hepatocellular carcinoma. Survival ranged from 1 month to over 20 months. Minor complications were seen. Only 15 out of 69 UK head and neck multidisciplinary teams offer electrochemotherapy. CONCLUSION: Electrochemotherapy is a well-tolerated adjunct to standard palliation of metastatic head and neck cancer, and is offered by a limited number of UK multidisciplinary teams.

Liver abscess after drug-eluting bead chemoembolization in patients with metastatic hepatic tumors.

OBJECTIVE: To investigate the incidence and risk factors for liver abscess formation after treatment with drug-eluting bead chemoembolization (DEB-TACE) in patients with metastatic hepatic tumors (MHT). METHODS: The current study is a retrospective analysis of the clinical data of 137 patients with metastatic hepatic tumors who received DEB-TACE treatment in our institute (Union Hospital, Tongji Medical College, Huazhong University of Science and Technology) between June 2015 and September 2020. Patients were evaluated for the presence or absence of post-DEB-TACE liver abscess. Univariate and multivariate analyses were used to identify risk factors for liver abscess formation. RESULTS: The incidence of liver abscess formation after the DEB-TACE procedure was 8.76% per patient and 5.53% per procedure. Univariate analysis showed that larger maximum tumor diameter (p = 0.004), Grade 1 artery occlusion (p < 0.001) and systemic chemotherapy within 3 months before the DEB-TACE procedure (p < 0.001) were all associated with liver abscess formation. However, only systemic chemotherapy within 3 months before the DEB-TACE procedure (OR 5.49; 95% CI 0.34-13.54; p < 0.001) was identified by multivariate analysis to be an independent risk factor. CONCLUSIONS: Tumor size, Grade 1 artery occlusion and recent systemic chemotherapy may all be associated with increased risk of liver abscess formation following DEB-TACE treatment in patients with metastatic hepatic tumors. ADVANCES IN KNOWLEDGE: Identification of risk factors for liver abscess formation following DEB-TACE in patients with MHT. These findings suggest the need for caution and consideration of the aforementioned risk factors on the part of interventional radiologists when designing DEB-TACE strategies and performing post-procedure patient management.

Hepatic tumours and radiotherapy.

We present the update of the recommendations of the French society of oncological radiotherapy on hepatic tumours. Recent technological progress led to develop the concept of focused liver radiation therapy. We must distinguish primary and secondary tumours, as the indications are restricted and must be discussed as an alternative to surgical or medical treatments. The tumour volume, its liver location close to the organs at risk determine the irradiation technique (repositioning method, total dose delivered, dose fractionation regimens). Tumour (and liver) breathing related motions should be taken into account. Strict dosimetric criteria must be observed with particular attention to the dose-volume histograms of non-tumoral liver as well as of the hollow organs, particularly in case of hypofractionated high dose radiotherapy "under stereotaxic conditions". Stereotactic body radiotherapy is being evaluated and is often preferred to radiofrequency for primary or secondary tumours (usually less than 5cm). An adaptation can be proposed, with a conformal fractionated irradiation protocol with or without intensity modulation, for hepatocellular carcinomas larger than 5cm.

[A Case of Liver Metastasis Complete Resection for Concurrent Overlapping Cancer of the Transverse Colon and Renal Cell Carcinomas that were Difficult to Differentiate from Hepatocellular Carcinoma].

A 79-year-old man visited the hospital because of constipation. Colonoscopy showed a transverse colon carcinoma. Dynamic CT showed a renal neoplastic lesion and 2 lesions in the liver with early staining and late wash out, and the liver lesions showed ring enhancement on EOB-MRI. The preoperative diagnosis was either transverse colon cancer, renal cell carcinoma, hepatocellular carcinoma, or metastatic liver cancer. The patient underwent partial transverse colon resection, partial right nephrectomy, and partial hepatic resection. Additional to the 2 liver lesions in S6, an intraoperative ultrasound showed 1 tumor in S5; therefore, 3 partial hepatectomies were performed. Histopathological findings revealed that the tumors in S5 and S6 were liver metastases of transverse colon cancer and renal cell carcinoma, respectively. The final diagnosis was transverse colon cancer, pT4a, pN0, pM1, pStage Ⅳa and papillary renal cell carcinoma, pT1a, pN0, pM1, pStage Ⅳ. For 9 months postoperatively, there was no apparent recurrence.

Development of hepatocellular carcinoma from various phases of chronic hepatitis B virus infection.

BACKGROUND & AIMS: There is insufficient data on the clinical course of chronic hepatitis B (CHB) patients in the immune-tolerant (IT) and immune-clearance, inactive (IC) phases over a long follow-up period. DESIGN: We enrolled 466 CHB patients from our historical cohort, including 56 IT+MA　 (mildly active), 134 IC, 230 with chronic active hepatitis (CH) and 46 with liver cirrhosis (LC), who were categorized to each phase by at least one year of follow-up period from the first visit to our hospital. We investigated long-term risks, and their factors, of developing hepatocellular carcinoma (HCC), and the transition between the clinical phases, especially in the IT+MA and IC groups. RESULTS: Of the 56 patients in the IT+MA group, 27 remained the IT+MA phase, but 29 transitioned to the CH phase and started nucleot(s)ide analogue (NA) treatment during the follow-up period. Meanwhile, of the 134 patients in the IC group, only 5 started NA treatment after progressing to the CH phase. The development of HCC from the IT+MA, IC, CH, and LC groups was observed in 2, 2, 9, and 20 cases, respectively. The cumulative incidence rates of developing HCC in the IT+MA, IC, CH, and LC groups were 9.9, 1.8, 3.0, and 53.1% at 10 years. In the CH and LC group, patients who developed HCC were older, had higher levels of FIB-4 index, M2BPGi, HBcrAg and AFP, and had lower levels of albumin and platelet counts. In CH patients, FIB-4 index levels were elevated at the diagnosis of HCC compared to baseline, whereas these decreased during the follow-up period in non-HCC patients. CONCLUSIONS: HCC occurred at a certain rate among patients in the IT+MA and IC groups. Careful follow-up is required for CH patients with higher levels of FIB-4 index and/or M2BPGi because of the high incidence of HCC development. (299 words).