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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.

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.

Background In non-small cell lung cancer, response rates to chemotherapy given after immune checkpoint inhibitors has been reported to be higher compared to response rates to chemotherapy given before immune checkpoint inhibitors. However, this phenomenon has not been reported in patients with gastrointestinal cancers nor with the use of multi-targeted kinase inhibitors. Case presentation We present a series of six patients who received multi-targeted kinase inhibitors or chemotherapy after progression on immune checkpoint inhibitors and showed unexpected response. Five of these patients had metastatic hepatocellular carcinoma and received salvage multi-targeted kinase inhibitors. Two of these five patients had no response to initial multi-targeted kinase inhibitors but had unexpected response to re-challenge with multi-targeted kinase inhibitors after immune checkpoint inhibitors exposure. The sixth patient had metastatic rectal cancer and showed response to salvage chemotherapy following immune checkpoint inhibitors. Conclusion We postulate that the sequencing of immune checkpoint inhibitors prior to other forms of systemic therapy may potentially lead to an immunomodulatory effect in gastrointestinal cancers with potential improvement in response rates.

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.

Introduction: The treatment of unresectable hepatocellular carcinoma (HCC) has radically changed after the approval of the combination of atezolizumab plus bevacizumab as first-line treatment. A st...

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.

The treatment of recurrent hepatocellular carcinoma (HCC) after liver transplantation is difficult due to the lack of effective treatment options. The available evidence on the emerging immunotherapy in liver transplantation is based on anecdotal experiences and requires additional investigations. To determine the efficacy and safety of immunotherapy in liver transplant recipients, we report three cases of recurrent metastatic HCC after liver transplantation who were treated with nivolumab as off-label salvage therapy.

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