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Immune checkpoint inhibitors are generally contraindicated for post-transplant patients. However, we report two patients with metastatic hepatocellular carcinoma (HCC) treated with camrelizumab (SHR-1210), an anti-programmed cell death 1 (PD-1) agent, after liver transplant. Before undergoing immunotherapy, both patients underwent liver allograft biopsy and obtained negative PD-L1 expression in tumor and liver graft specimens by immunohistochemistry. Then, camrelizumab (200 mg) was administered once every 3 weeks. During immunotherapy, the targeted therapy was continued, and the immunosuppression regimen was adjusted to a low-dose level. No graft rejection or other severe adverse reactions were observed. The disease remained stable (SD, mRECIST) for 3 months in one patient and 10 months in the other. Therefore, camrelizumab may have safety and potential benefits in advanced HCC after liver transplant.

Hepatocellular carcinoma (HCC) is a common, primary malignant liver disease that usually metastasizes to the lungs, followed by the abdominal lymph nodes and brain. However, extrahepatic metastasis to the maxillofacial area is uncommon and predominates in the mandible, so HCCs in the maxilla or temporal bone from a primary hepatic lesion are extremely rare. We present a case of HCC in the maxilla and temporal bone in a 52-year-old male, which was first suspected to be a squamous cell carcinoma after computed tomography but was confirmed as a metastasis related to his primary HCC after fine-needle aspiration biopsy followed by immunohistochemical analysis.

Metastasis of hepatocellular carcinoma (HCC) to the seminal vesicle is extraordinarily rare, with only two other cases reported in the literature. Herein we present the first documented case of a seminal vesicle as the initial site of solitary metastasis in a patient with a history of liver transplantation for HCC. We aim to provide more information regarding the disease process, histopathology, and management strategy.

Background: Until recently, advanced HCC patients with major vessel and cardiac involvement have had an extremely poor prognosis without satisfactory treatment. Case presentation: A 63-year-old Taiwanese male presented with metastatic HCC with RA and IVC thrombi, as well as pulmonary metastases that were successfully treated by multimodal management, encompassed by surgical thrombectomy, concurrent systemic sorafenib and locoregional therapies, and immunotherapy. The patient has achieved a complete response over the past 33 months. Conclusions: Through this case report, which shows a successful outcome via multimodal management, a more aggressive approach should be considered when a patient is expected to tolerate the risks and side effects of various treatments.

Tumor lysis syndrome is a potentially lethal complication of chemotherapy, usually associated with aggressive hematologic malignancies. We describe the case of a young patient with metastatic hepatocellular cancer who developed rapid and fatal tumor lysis syndrome following initiation of sorafenib therapy. Although rare with sorafenib therapy for hepatocellular carcinoma, tumor lysis syndrome is serious complication. Patients with a high burden of disease at therapy initiation should have their metabolic parameters measured prior to starting therapy and closely followed for the first 1–2 weeks while being treated.

We read with great interest the article titled “ Multidisciplinary management of recurrent and metastatic hepatocellular carcinoma after resection: an international expert consensus ” (1) published in HepatoBiliary Surgery and Nutrition . Recurrence can follow all treatments, representing a major challenge in treating hepatocellular carcinoma (HCC), as well as the main cause of death following surgery. Presently, guidelines and recommendations for primary HCC are clearly laid out, but recurrent HCC (RHCC) guidelines remain to be established—even though 70% of patients have recurrence within 5 years (2). This highlights the need for practical, stratified guidelines for continued management of these patients.

Background Lenvatinib, a newly developed oral multi-tyrosine kinase inhibitor, has amazing potential in the multidisciplinary treatment of advanced or metastatic hepatocellular carcinoma. Thrombocytopenia is a serious adverse event that causes drug dose reduction or withdrawal. Partial splenic embolization is currently being used as a non-surgical treatment for thrombocytopenia caused by various pharmacotherapies. Case report Partial splenic embolization was performed for three patients with hepatocellular carcinoma receiving lenvatinib therapy with/without transarterial chemoembolization. Partial splenic embolization was advantageous for various situations, including the induction of lenvatinib for patients with thrombocytopenia, application of lenvatinib after multiple transarterial chemoembolization using cisplatin and radiotherapy, and re-administration of lenvatinib after lenvatinib therapy-induced thrombocytopenia. In all cases, lenvatinib therapy was completed without need for cessation due to thrombocytopenia. Conclusion We strongly recommend the new concept of combining partial splenic embolization and lenvatinib therapy for hepatocellular carcinoma.

PURPOSE Donafenib, a novel multikinase inhibitor and a deuterated sorafenib derivative, has shown efficacy in phase Ia and Ib hepatocellular carcinoma (HCC) studies. This study compared the efficacy and safety of donafenib versus sorafenib as first-line therapy for advanced HCC. PATIENTS AND METHODS This open-label, randomized, parallel-controlled, multicenter phase II-III trial enrolled patients with unresectable or metastatic HCC, a Child-Pugh score ≤ 7, and no prior systemic therapy from 37 sites across China. Patients were randomly assigned (1:1) to receive oral donafenib (0.2 g) or sorafenib (0.4 g) twice daily until intolerable toxicity or disease progression. The primary end point was overall survival (OS), tested for noninferiority and superiority. Efficacy was primarily assessed in the full analysis set (FAS), and safety was assessed in all treated patients. RESULTS Between March 21, 2016, and April 16, 2018, 668 patients (intention-to-treat) were randomly assigned to donafenib and sorafenib treatment arms; the FAS included 328 and 331 patients, respectively. Median OS was significantly longer with donafenib than sorafenib treatment (FAS; 12.1 v 10.3 months; hazard ratio, 0.831; 95% CI, 0.699 to 0.988; P = .0245); donafenib also exhibited superior OS outcomes versus sorafenib in the intention-to-treat population. The median progression-free survival was 3.7 v 3.6 months ( P = .0570). The objective response rate was 4.6% v 2.7% ( P = .2448), and the disease control rate was 30.8% v 28.7% (FAS; P = .5532). Drug-related grade ≥ 3 adverse events occurred in significantly fewer patients receiving donafenib than sorafenib (125 [38%] v 165 [50%]; P = .0018). CONCLUSION Donafenib showed superiority over sorafenib in improving OS and has favorable safety and tolerability in Chinese patients with advanced HCC, showing promise as a potential first-line monotherapy for these patients.

Metastatic hepatocellular carcinoma (HCC) can involve the lung parenchyma. However, predominant thoracic lymphadenopathy involvement is less described and there are multiple alternative malignant and non‐malignant causes of a similar appearance. Accurate tissue diagnosis is important to determine appropriate management and prognostication. Here, we report two cases of metastatic HCC recurrence causing large thoracic lymphadenopathy, diagnosed adequately and safely by linear endobronchial ultrasound (EBUS) transbronchial needle aspiration., Hepatocellular carcinoma (HCC) metastasis to predominantly thoracic lymph nodes is uncommon. Here, we report two cases of metastatic HCC recurrence causing large thoracic lymphadenopathy, diagnosed adequately and safely by linear endobronchial ultrasound (EBUS) transbronchial needle aspiration.

Introduction: The incidence of liver cancer is very high in China, and it is more common in patients with a history of hepatitis B.Most patients with liver cancer have distant metastasis at the time of visiting, but parotid metastasis is very rare. We report a patient with parotid enlargement who was diagnosed with multiple metastasis of liver cancer. Presentation of Case: A 52-year-old male presented with parotid enlargement for one month.after the right deep maxillofacial neck mass was cut and biopsied,Metastatic hepatocellular carcinoma of the parotid gland associated with multiple metastasis was diagnosed. Discussion: Metastasis of liver cancer to the parotid gland is very rare, to date, only 7 cases HCC metastasis to the parotid gland have been reported, this case is the first report in China. For patients with parotid enlargement at the first diagnosis, no history of hepatitis or liver cancer, and normal or slightly elevated AFP,It is very easy to misdiagnose and miss diagnosis.Pathological diagnosis and complete systemic examination are very important in the diagnosis of tumor.Although very rare, parotid metastases in HCC should be maintained with high suspicion.

Background This study aims to evaluate the clinicopathological characteristics of metastatic hepatocellular carcinoma (HCC) patients and develop nomograms to predict their long-term overall survival (OS) and cancer-specific survival (CSS). Methods Information on metastatic HCC from 2010 to 2015 was retrieved from the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute. The metastatic HCC patients were divided into a long-term survival (LTS) group and a short-term survival (STS) group with 1 year selected as the cut-off value. Then, we compared the demographic and clinicopathological features between the two groups. Next, all patients were randomly divided into a training group and validation group at a 7:3 ratio. Univariate and multivariate Cox regression analyses were used to identify potential predictors for OS and CSS in the training group, and nomograms of OS and CSS were established. These predictive models were further validated in the validation group. Results A total of 2163 patients were included in the current study according to the inclusion and exclusion criteria. Patients with characteristics including lower T stage and N stage; treatment with surgery, radiation or chemotherapy; no lung metastasis; and AFP negative status showed better survival. The concordance index (C-index) of the OS nomogram was 0.72 based on 9 variables. The C-index of the CSS nomogram was 0.71 based on 8 variables. Conclusions These nomograms may help clinicians make better treatment recommendations for metastatic HCC patients.

Hepatoid adenocarcinoma of the lung is a rare subtype of lung cancer. We report a case of a metastatic hepatoid adenocarcinoma of the lung with aggressive behavior, including biopsy and autopsy findings. The pulmonary tumors showed features indistinguishable from hepatocellular carcinoma and were diffusely positive for Hepatocyte Paraffin 1.

Key Clinical Message In patients with known risk factors for hepatocellular carcinoma and an elevated AFP, the diagnosis should remain on the differential even in the absence of hepatic lesions. High index of suspicion is needed, and aggressive diagnostic approaches are needed to not miss this entity.

// Mehran Afshar 1 , Peter Fletcher 2 , Antonio D Bardoli 3 , Yuk Ting Ma 4, * and Pankaj Punia 5, * 1 Oncology, St George’s University Hospitals NHS Foundation Trust, London, UK 2 Cancer Research UK Clinical Trials Unit, Birmingham, UK 3 College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK 4 Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK 5 Oncology, Queen Elizabeth Hospital Birmingham, Birmingham, UK * These authors contributed equally to this work Correspondence to: Pankaj Punia, email: Pankaj.Punia@uhb.nhs.uk Keywords: neutrophil lymphocyte ratio (NLR); alpha-fetoprotein (AFP); hepatocellular carcinoma; sorafenib; survival Received: July 31, 2017 Accepted: February 27, 2018 Published: March 30, 2018 ABSTRACT Background: Sorafenib is the current standard of care for patients with advanced or metastatic hepatocellular carcinoma. Currently no universally agreed model exists correlating the Neutrophil Lymphocyte ratio (NLR) and non-secretion of AFP with the survival of HCC patients treated with sorafenib. Patients and Methods: We retrospectively analysed patient records with a confirmed diagnosis of HCC treated with sorafenib between April 2009 and March 2014. Survival analysis was performed using the Kaplan–Meier method and Cox regression. Results: Patients separated into groups based on NLR (≤3 or >3), or AFP secretion profile ( 3.0 it was 6.0 months (95% CI: 4.9–8.2 months) [HR 1.32 (95% CI: 0.96–1.80)]. The median overall survival post sorafenib was higher in the “non-secretor” AFP group. OS for AFP

Dear Editor,Hepatocellular carcinoma (HCC) accounts for 0.5% of all childhood cancers.1,2 Prognosis is generally poor depending mainly on local extension and metastatic disease.2 Surgical resection...

Sorafenib is widely used for unresectable and metastatic hepatocellular carcinomas. Radiation recall dermatitis (RRD) is an acute inflammatory reaction confined to previously irradiated skin that occurs after the administration of certain drugs. RRD after sorafenib treatment is rare; five cases have been reported thus far. We describe a 44-year-old man irradiated for chest wall bone metastasis from hepatocellular carcinoma. Eight days after radiotherapy completion, systemic therapy for metastatic hepatocellular carcinoma was initiated with sorafenib treatment. Eleven days after starting sorafenib, the patient complained of erythematous rash with pruritus in the chest wall, in a location consistent with the previous radiation field. Sorafenib was continued at the same dose, despite the RRD. The skin reaction subsided over the next 2 weeks without any medical intervention.

Hepatocellular carcinoma (HCC) metastasizing to the esophagus and mimicking as a primary tumor of the esophagus is extremely rare, being present in

Management of hepatocellular carcinoma (HCC) generally follows EASL-EORTC clinical practise guideline. We report a case of a 50-year-old man who had multinodular HCC with lung metastases, whose management had deviated from the standard guideline but still survive 5 years after initial diagnosis.

Metastatic tumor involvement of the heart is uncommon but may occur with all types of primary neoplasms. We report the case of a 51-year-old male who developed a massive mass involving the upper right pulmonary vein. The tumor was removed and the final pathology report disclosed metastatic hepatocellular carcinoma. Hepatocellular carcinoma affecting the pulmonary veins is a very rare condition.

Although immunotherapy is a successful approach in oncology, it might be detrimental to some patients. In the condition of hyperprogression, patients experience accelerated progression after immunotherapy, resulting in a worse outcome. Hyperprogression may be difficult to be identified in the early stage. Once the diagnosis is confirmed in the follow-up evaluation, the immunotherapy should be stopped immediately. In this case, we report a hyperprogression patient during combined immunotherapy toward metastatic hepatocellular carcinoma observed by serial F-FDG PET.

Background Early diagnosis decreases the mortality of hepatocellular carcinoma (HCC). We aimed to investigate the usefulness of PIVKA‐II, AFP, AFP‐L3, CEA, and their combinations in the diagnosis of primary and metastatic HCC. Methods One hundred and twenty patients with primary HCC (PHC), 115 with metastatic HCC (MHC), 89 with chronic liver disease (CLD), and 116 healthy volunteers were included. The diagnostic values of each marker and their combinations for HCC diagnosis were represented by ROC curve analyses. Results PIVKA‐II, AFP, and AFP‐L3 levels in PHC group were higher than that in normal control, CLD, and MHC groups. CEA levels in MHC group were higher than that in the other three groups. When the four markers were analyzed individually, PIVKA‐II showed the highest positive rate in PHC group (76.7%) and CEA showed the highest positive rate in MHC group (69.6%). PIVKA‐ II showed the largest area under ROC curve (AUC = 0.835) to discriminate PHC group from CLD group. Combined PIVKA‐II with AFP‐L3 increased the AUC to 0.910. CEA showed the highest AUC (0.849) to discriminate MHC group from CLD group. Combined CEA with PIVKA‐II increased the AUC to 0.866. AFP‐L3 alone showed the highest AUC (0.890) to discriminate MHC group from PHC group. Combined PIVKA‐II with AFP‐L3, and CEA increased the AUC to 0.957. Conclusion PIVKA‐II, AFP‐L3, AFP, and CEA are effective biomarkers for the diagnosis of PHC and MHC. Their combinations could improve the diagnostic performance compared with each marker used alone in detecting PHC and MHC.

Trans-arterial radioembolization (TARE) with Y-90 microspheres is an endovascular, liver-directed therapy suitable for treatment of locally advanced hepatocellular carcinoma (HCC) often as a way to reduce tumor size and bridge patients to resection or liver transplant. Opdivo®, or nivolumab, a programmed cell death protein 1 (PD-1) inhibitor, is an immunotherapeutic drug approved in September 2017 for the treatment of HCC in patients who have received prior sorafenib. We report on a patient with hepatocellular carcinoma with right and left portal vein involvement, bony metastasis, and possible lung metastasis. The patient showed a significant response following consecutive treatment with TARE, sorafenib, and nivolumab. Our case suggests that TARE, sorafenib, and nivolumab may have a synergistic effect on the immune response to HCC.

The diagnosis of primary hepatocellular carcinoma (HCC) in high risk patients, such as those with chronic hepatitis B or C with/without cirrhosis of the liver, can be made with relevant image studies alone; however, morphologic confirmation by cytology or histopathology is essential to the diagnosis of metastatic HCC because the treatment of the latter differs from that of primary extrahepatic malignancy. Although both cytology and histopathology are important tools in the diagnosis of malignancy, histopathology almost always plays a confirmatory and pivotal role, and also a gold standard in cyto-histological correlation. We present two patients of metastatic HCC to rare sites; endobronchus in one, and neck lymph nodes, face and the abdominal wall in the other. Repeated bronchial biopsy in the first patient and excisional biopsy from the metastatic sites of the second patient failed to make a conclusive diagnosis of metastatic HCC. However, bronchial brushing in the first patient and fine needle aspiration cytology from the respective metastatic sites of the second patient consistently showed characteristic HCC features and provided clinicians with the rationale for ongoing treatment. The diagnostic issues and possible pitfalls are discussed. Cytology and histopathology appear equipollent; sometimes cytology can play a diagnostic role when histopathology fails its expected role in this scenario.

Introduction To retrospectively evaluate the efficacy and safety of salvage resection(SR) for recurrence or metastasis of hepatocellular carcinoma (HCC) after initial percutaneous ablation therapy (PAT). Methods From September 2006 to September 2013, 50 consecutive patients who received SR for recurrent or metastatic HCC undergone initial PAT were enrolled. Safety and efficacy of SR for these patients were analyzed. Results No treatment-related death occurred. Curative outcome was achieved in all the patients. The median overall survival after SR was 40 months, and the 1-, 3-, 5-year overall survival rate after SR was 85.2%, 46.4% and 34.8%, respectively. The disease-free survival was 38.6% at 1 year and 12.1% at 3 years after SR. Conclusion SR is an effective and safe method for patients with recurrent or metastatic HCC after initial PAT treatment.

279 Background: Several therapies have recently gained regulatory approval in the United States (US) as second-line (2L) treatment options for patients with advanced unresectable or metastatic hepatocellular carcinoma (HCC). Treatment patterns and associated outcomes in a real-world population, especially in the contemporary era, remain understudied. Methods: This retrospective study utilized electronic health record data collected during routine patient care in outpatient oncology practices in the US. Adult patients diagnosed with advanced/ metastatic HCC between April 2017 and January 2020 were identified from the Concerto HealthAI database. Patients who survived at least one month from the end of first-line (1L) systemic therapy but did not initiate 2L therapy were classified as having received supportive care alone (SCA). Demographics, patient and disease characteristics, treatment patterns, and outcomes were described descriptively. Median overall survival (OS) from initiation of 2L therapy or end of 1L therapy for patients receiving SCA until death was estimated by the Kaplan-Meier method. Results: A total of 586 patients with advanced/ metastatic HCC were identified in the database. 330 patients received 1L therapy, and of those patients 63% (N= 207) received systemic 2L therapy (n= 105) or SCA (n= 102). At first diagnosis of advanced/ metastatic HCC, the median age was 64 years, and 86% were male. Of patients with ECOG status available at diagnosis (67%), 45% had ECOG status 0-1. The most common 1L agents prescribed were sorafenib (n= 126, 61%), lenvatinib (n= 28,14%) and sorafenib + nivolumab (n= 13, 6%) The most frequent agents prescribed in 2L were nivolumab (n= 44, 42%), sorafenib (n=18,17%), and lenvatinib (n=9, 9%). The median OS of patients receiving any systemic 2L therapy was 7.7 months (95% confidence interval 5.7-11.1) from time of receiving 2L therapy, whereas the median OS of patients receiving SCA was 5.0 months (95% confidence interval 3.3-7.1) from time of end of 1L therapy. Conclusions: In this contemporary national real-world cohort of patients with advanced/ metastatic HCC, a third of patients who received 1L therapy subsequently received 2L therapy. Next steps include investigating factors associated with non-receipt of 2L therapy, sequencing of therapies when multiple lines of therapies are received, and evaluating outcomes by type of agent received in 2L and beyond.

295 Background: In May 2020, atezolizumab plus bevacizumab was approved by US Food and Drug Administration for patients with unresectable or metastatic hepatocellular carcinoma (HCC) who have not received prior systemic therapy due to improvement in overall and progression-free survival compared with standard sorafenib treatment. However, because of the high cost of atezolizumab plus bevacizumab, there is a need to assess its value by considering both efficacy and cost. The aim of this study is to evaluate the cost-effectiveness of atezolizumab plus bevacizumab vs sorafenib for patients with unresectable or metastatic HCC from the US payer perspective. Methods: A partitioned-survival model was developed to compare health care costs and clinical outcomes of atezolizumab plus bevacizumab vs sorafenib in first-line treatment of unresectable or metastatic HCC over 6-year horizon. Treatment effects were extracted from the IMbrave150 trial. Health care cost and health utility data were obtained from published studies and databases. Incremental cost-effectiveness ratio (ICER) was calculated as the ratio of the incremental cost to the incremental quality-adjusted life years (QALYs). One-way deterministic and probabilistic sensitivity analyses were used to examine model uncertainty. Additional subgroup analyses were performed. Results: Atezolizumab plus bevacizumab resulted in increase of 0.623 life-years, 0.484 QALYs and $158,781 per patient at the base case analysis. The ICER was $322,500 per QALY (95% confidence interval, $136,275 to $801,509 per QALY), with 0.5% and 4.1% chance of being cost-effective at a willingness-to-pay threshold of $100,000 and $150,000 per QALY, respectively. The ICER never went below $150,000 per QALY in the one-way sensitivity analyses and among patients of clinically relevant subgroups in the subgroup analyses. Conclusions: Atezolizumab plus bevacizumab is unlikely to be cost-effective compared with sorafenib in first-line treatment of patients with unresectable or metastatic HCC from the US payer perspective.

Hepatocellular carcinoma (HCC) is the sixth-most common cancer and the third leading cause of cancer-related death in the world. However, 40-70% patients eventually suffer from postoperative recurrence within 5 years. HCC recurrence after surgery severely affects prognosis of the patients. Nevertheless, there is an opportunity to improve patients' prognosis if doctors and researchers can recognize the importance of a standardized perioperative management and study it in clinical and pre-clinical settings. Hence, based on our own experience and published studies from other researchers, we develop this consensus regarding multidisciplinary management of locally recurrent and metastatic hepatocellular carcinoma after resection. This consensus consists of the entire course of recurrent hepatocellular carcinoma (RHCC) management, including prediction of recurrence, prevention, diagnosis, treatment and surveillance of RHCC. Consensus recommendations are presented with grades of evidences (Ia, Ib, IIa, IIb, III and IV), and strength of recommendations (A, B, C, D and E). We also develop a decision-making path for RHCC treatment, which can intuitively demonstrate the management for RHCC. It is hoped that we may make some effort to standardize the management of RHCC and ultimately understand how to improve outcomes.

Supplemental Digital Content is available in the text, In the present study, we aimed to investigate the survival benefit from definitive local treatment (LT) for hepatocellular carcinoma patients with distant metastasis (mHCC). We retrospectively analyzed mHCC patients from Surveillance, Epidemiology, and End Results (SEER) Database. The patients’ clinical and pathological characteristics were analyzed. Overall survival (OS) was calculated by Kaplan-Meier method. Independent risk factors associated with disease special mortality (DSM) were identified by multivariable regression analysis. A total of 7187 mHCC patients from SEER database were identified. A total of 258 (3.6%) patients had received surgery treatment (ST), 64 (0.9%) patients underwent radiotherapy (RT), and 6865 (95.5%) patients were identified to no surgery or radiation therapy group (NSR). Compared with the patients in NSR group, patients who received ST (hazard ratio [HR]: 0.26, 95% confidence interval [CI] 0.22–0.31, P 50 years, female, and T3 or higher stage were associated with increased DSM. The present study demonstrated the survival benefit of definitive LT in mHCC patients. However, a large randomized clinical trial to validate the role of LT in mHCC is necessary in the future.

Hepatocellular carcinoma (HCC) is the sixth most common neoplasm worldwide; HCC metastasis is common affecting 50% of cases. However, metastasis to the oral cavity is extremely infrequent. We present a case of hepatocellular cancer first presenting as a mass lesion at the upper alveolus and review metastatic hepatocellular carcinoma to the oral cavity in 73-year-old male patient. Keywords: Oral cavity, Hepatocellular carcinoma