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Objective: To evaluate the feasibility, efficacy and safety of transcatheter arterial chemoembolization (TACE) with HepaSphere for patients with pulmonary or mediastinal metastases from hepatocellular carcinoma (HCC). Methods: Between June 2009 and January 2018, 14 patients with pulmonary or mediastinal metastases from HCC were treated with TACE with a combination of 1–3 chemotherapeutic drugs followed by HepaSphere embolization. As first end point, local tumor response and adverse events were evaluated after the first session of TACE, with Response Evaluation Criteria In Solid Tumors v. 1.1 and Common Terminology Criteria for Adverse Events v. 4 criteria, respectively. Overall survival was evaluated as secondary end point. TACE was repeated on-demand. Results: TACE with HepaSphere was well tolerated with acceptable safety profile and no 30 day mortality. 1 month objective response and disease control rate were calculated to be 7.1 and 100%, respectively. Mean tumor size reduction rate was 15.6±9.5% at the first month. Two Grade 3 cytopenia events were seen (14.3 %), however none of the Grade 2 or more post-embolization syndrome was observed. The median overall survival time was 15.0 months and the 1 year, 3 year and 5 year survival rate were, 57.1%, 28.6%, 19.1%, respectively. Conclusion: Early experience showed that the transarterial treatment with HepaSphere is safe and effective treatment for patients with pulmonary or mediastinal metastases from HCC. Advances in knowledge: Currently, the effects of molecular targeted drugs on HCC metastases are limited and side-effects are relatively frequent. In the present study, transarterial treatment might be a promising treatment for HCC metastasis.

Previous reports on transarterial treatment for lung cancer were reviewed. The bronchial arterial infusion therapy has a long history since 1964. Better local control with less doses of anti-neoplastic agents was warranted by trying transarterial administration to lung and mediastinal tumors. It is reported that both primary and metastatic tumors are fed by bronchial or other systemic arteries. The bronchial arterial embolization for hemoptysis has been introduced for clinical practice since 1973. Hemoptysis by not only benign but also malignant diseases has been well controlled by embolization. In recent decades, the technical elements for transarterial treatments have markedly improved. They make it possible to carry out precise procedures of selective catheter insertion to the tumor relating arteries. Current concepts of transarterial treatment, technical aspects and treatment outcomes are summarized. Tentative result from chemo-embolization for advanced lung cancer using recent catheter techniques was also described. It provides favorable local control and survival merits. It is considered that a population of lung cancer patients can benefit from transarterial management using small doses of anti-neoplastic agents, with less complications and less medical costs.

Very few studies have been published on the long-term histopathologic follow-up of spherical embolic agents after their injection. To our knowledge, there are no reports in the literature regarding pathological analysis of the transvascular migration of HepaSphere particles. We here report a case of a patient with hepatocellular carcinoma (HCC) who underwent liver transplantation 12 months after drug eluting microsphere transcatheter arterial chemoembolization (DEM-TACE), and long-term histopathologic follow-up of the microspheres was performed. Furthermore, to our knowledge, this is the first report in which transvascular migration of a HepaSphere particle was confirmed histologically. A 60-year-old male with chronic hepatitis B was treated with entecavir and seroconversion was obtained. The patient had decompensated cirrhosis, and desired to undergo living donor liver transplantation (LDLT). However, 2 HCC tumors of 3  cm or less were detected in his liver. The transplantation surgeon proposed DEM-TACE as a bridge therapy. The HCCs were located in the right lobe and lateral segment of the liver. A 1.9  F preshaped microcatheter (ProgreatΣ, Terumo, Japan) was selectively inserted into the A3 and anterior segmental branch, 10  mg of epirubicin was injected into each artery, and the arteries were embolized with 7  mg and 13  mg of HepaSphere loaded with epirubicin, respectively. Two months later, contrast-enhanced CT displayed a complete response. At that time, lung metastasis was suspected, but after partial lung resection, the patient was diagnosed as having inflammatory granuloma. One year after DEM-TACE treatment, LDLT was performed. No cancerous cells were detected in the area where the tumor was present, but 22 HepaSphere particles were detected. All particles were present in the interstitium. Furthermore, the transvascular migration of a HepaSphere particle was histologically confirmed. The largest and smallest HepaSphere diameters were 241.6  ±  52.5  µm and 186.5  ±  41.4  µm, respectively, and deformity was 22.6% ± 13.0 %. All the HepaSpheres detected in the examined pathological specimen were noted to be extravascular.

The aim of the present study was to determine the optimal dose and optimal target volume for marginal zone lymphoma of the ocular adnexa. Between January, 2008 and December, 2013, 40 patients with histologically proven primary marginal zone lymphoma of the ocular adnexa who underwent radiotherapy at the Tokyo Medical University were evaluated. The prescribed dose was 30 Gy in 15 fractions to the iso-center. Doses to the gross tumor volume (GTV), conjunctiva, bulbus oculi, retina and retrobulbar space were investigated, and the association between dose-volume factors and clinical outcome was analyzed. The overall and local progression-free survival rates at 3 and 5 years were 100% during a median observation period of 32 months. Two patients relapsed in the contralateral ocular adnexa. The progression-free survival rates at 3 and 5 years were 100 and 93.3%, respectively. The mean dose was 2.0 and 1.9 Gy for targets receiving 95% of the GTV dose (D95). The minimum dose was 0.9–2.0 Gy (median, 1.8 Gy). Thus, primary marginal zone lymphoma of the ocular adnexa favorably responded to lower doses of radiation, compared with prescribed doses to the iso-center. A radiation dose of 27 Gy in 15 fractions at D95 of GTV appeared to be optimal.