Feasibility Study of Transarterial Chemotherapy Followed by Chemoembolization for Recurrent Breast Cancer.

PURPOSE: To assess the treatment response to transarterial chemotherapy followed by chemoembolization for locally recurrent breast cancer. MATERIALS AND METHODS: Thirty-nine women with locally recurrent breast cancer after standard therapy underwent selective intra-arterial chemotherapy followed by embolization using drug-eluting microspheres for locally recurrent tumors and axillary lymph node metastases. Tumor response and toxicity were assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) and Common Terminology Criteria for Adverse Events (CTCAE), and survival was evaluated by the Kaplan‒Meier method. RESULTS: The local responses of breast tumors at 3 and 6 months were as follows: complete response, 5.1% and 7.2%; partial response, 35.9% and 67.8%; stable disease, 59.0% and 21.4%; and progressive disease, 0.0% and 3.6%, respectively. All adverse events were mild and did not require treatment. The median overall survival (OS) was 46.5 months, and the OS rates for 1 and 2 years were 81.4% and 69.2%, respectively. The size of recurrent tumors and axillary lymph node metastases did not impact prognosis, but both liver and bone metastases adversely affected survival. CONCLUSION: Transarterial chemotherapy followed by chemoembolization may provide a favorable tumor response in patients with locally recurrent breast cancer in whom conventional therapy has failed.

[Microsphere TACE with Arterial Infusion of Bevacizumab for Portal Vein Tumor Thrombus by Hepatocellular Carcinoma].

The successful treatment of 2 cases of portal vein tumor thrombus caused by hepatocellular carcinoma was reported. It is difficult to manage portal vein tumor thrombi by conventional transarterial chemoembolization(c-TACE)using lipiodol and a gelatin sponge. On the other hand, drug-eluting-microsphere TACE(DEM-TACE)can preserve hepatic function by maintaining the capillary circulation of sinusoids and the peribiliary arterial plexus. Even in cases of portal vein tumor thrombus, DEM-TACE could be safely performed without hepatic infarction. Bevacizumab, anti-VGEF monoclonal antibody, was injected into hepatic arteries with anti-neoplastic agents, followed by the epirubicin-loaded superabsorbent polymer microsphere( HepaSphere). The tumor thrombi in 2 cases were successfully eliminated after treatment for more than 2 years without deterioration of the hepatic function.

Transarterial management of advance lung cancer.

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.

[Transcatheter Arterial Chemoembolization with HepaSphereTM for Gastric Cancer with Mediastinal Lymph Node Metastases Causing Esophageal Compression and Dysphagia-A Case Report].

A 50s man was diagnosed with esophagogastric junction cancer. Simultaneously, PET-CT demonstrated mediastinal lymph node metastases. Two months later, 4 courses of systemic chemotherapy(SOX)were provided as preoperative therapy. However, the outcome was PD; therefore, radical gastrectomy could not be performed. Two more months later, esophageal dysphagia developed. Mediastinal lymph nodes that compressed the esophagus and the primary lesion of the cardia were considered to be the causes of dysphagia, and transcatheter arterial chemoembolization targeting those 2 lesions was performed. Cisplatin 20 mg, docetaxel 20 mg, and 5-FU 250mg were the drugs administered. These drugs were injected from the right bronchial artery, left gastric artery, and left phrenic artery, followed by mild embolization with HepaSphereTM. The mediastinal lymph nodes shrunk significantly, and dysphagia improved with 2 sessions. The primary lesion was found to have reduced in size with 6 sessions. Currently, no regrowth of the mediastinal lymph nodes has been observed 16 months(9 sessions) after the first session, and control of the primary lesion has been obtained.

[Transcatheter Arterial Chemoembolization with HepaSphereTM for Diffuse Liver Metastases from Prostatic Cancer without Elevation of the Serum Prostate-Specific Antigen Level-A Case Report].

Although postoperative recurrence or prostate cancer metastasis is usually accompanied by high prostate-specific antigen (PSA)levels, it may occur even if PSA level is within the normal range. Neuroendocrine differentiation(NED), which is one of such cases, causes rapid disease progression. A man in his 70s underwent total prostatectomy for prostate cancer with high PSA levels. Twenty-two months later, liver, lung, and bone metastases appeared even though the PSA levels were normal. The levels of both neuron-specific enolase and pro-gastrin-releasing peptide were elevated and the patient was clinically diagnosed with NED. Although systemic chemotherapy was administered, the outcome was progressive disease. Transcatheter arterial chemoembolization(TACE)was opted because liver metastases were one of the prognostic factors. Four types of chemotherapy drugs(cisplatin 20 mg, docetaxel 20 mg, 5-FU 250 mg, and bevacizumab 100 mg)were infused through the right and left hepatic arteries, followed by embolization with HepaSphereTM. The liver tumors were remarkably reduced in size and the levels of tumor markers were reduced in 5 sessions. This treatment would avoid the lethal liver trouble; however, the patient died 7 months after the first session of TACE.

Transarterial chemoembolization for pulmonary or mediastinal metastases from hepatocellular carcinoma.

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.

Long-term Histopathologic Follow-up of a Spherical Embolic Agent; Observation of the Transvascular Migration of HepaSphereTM.

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.

Coil Embolisation for Endovascular Treatment of Proper Hepatic Artery Aneurysm Using the Balloon Occlusion Technique.

INTRODUCTION: Endovascular repair (ER) as a minimally invasive approach can be effective for treating hepatic artery aneurysm (HAA) with gratifying results. Microcoil embolisation is the main technique used in ER. However, the coil embolisation of a large proper HAA (PHAA) with a very wide neck tends to be extremely troublesome owing to the limited length of the inflow and outflow artery. Moreover, it is difficult because of rapid blood flow in the proper hepatic artery (PHA) and the difficulty in preserving its branch flow. Microcoil embolisation of the inflow and outflow of a PHAA with the balloon occlusion technique through an originally developed single guiding sheath system was performed successfully. REPORT: A 73 year old woman was diagnosed with large PHAA (65 mm) by computed tomography examination. The PHAA was successfully treated by endovascular embolisation with microcoils using the balloon occlusion technique through a single guiding sheath system. DISCUSSION: This method is safe and effective for the treatment of a large PHAA.

Evaluation of patients who underwent percutaneous transhepatic portal vein embolisation by Tc-99m GSA scintigraphy.

PURPOSE: To analyse the correlation between the fold change in residual liver volume (RLV) and residual liver uptake at 15 (RLU15) before and after percutaneous transhepatic portal vein embolisation (PTPE). MATERIAL AND METHODS: Between August 2010 and December 2016, 20 patients who underwent PTPE were retrospectively selected. Before and three weeks after PTPE, contrast-enhanced computed tomography (CECT) and Tc-99m GSA scintigraphy were performed to analyse the fold changes in RLV and RLU15, respectively, as well as their correlation. RESULTS: After PTPE, a significant increase was observed in the RLV (before: 464 ±â€…99 ml; after: 573 ±â€…118 ml, p = 0.004) and the RLU15 (before: 11.0 ±â€…2.9%; after: 17.7 ±â€…3.8%, p = 5 × 10-7). The fold increase of RLV and RLU15 in all patients was 1.25 ±â€…0.15 and 1.66 ±â€…0.33, respectively. No significant correlation was observed in the fold increase in both RLV and RLU15 (r = 0.14, p = 0.66). In patients no. 3 and 9, who were outliers, the increase in RLV was minimal and RLU15 increased greatly, and these 2 patients underwent radical hepatectomy after PTPE. CONCLUSIONS: No correlation was observed between the fold increase in RLV and RLU15 before and after PTPE. In order to accurately evaluate the residual liver function, it should be considered necessary to evaluate not only by morphological CECT volumetry, but also by functional outcome of Tc-99m GSA scintigraphy.Residual liver volume may not necessarily reflect RLF. It may be possible to improve the radical resection rate by detecting the potential increase of RLF with RLU15 of Tc-99m GSA scintigraphy.

Successful recanalization of acute extensive portal vein thrombosis by aspiration thrombectomy and thrombolysis via an operatively placed mesenteric catheter: a case report.

Portal vein thrombosis (PVT) after hepatobiliary surgery is rare but can cause lethal and severe complications. If early diagnosis and recanalization can be achieved, the PVT is expected to be eliminated. A 70-year-old male was diagnosed as having hepatocellular carcinoma occupying the right lobe of the liver. As oligometastatic lung tumors were simultaneously detected on contrast-enhanced CT (CECT), hepatectomy was not indicated. However, the primary tumor was very large, and as large tumor size can be associated with an unfavorable prognosis, and owing to the strong desire of the patient, he underwent right lobe hepatectomy. Jaundice appeared on post-operative Day (POD) 2 and CECT displayed slight intraheptatic bile duct dilation. However, a PVT did not exist at this time. Percutaneous transhepatic biliary drainage was performed and Doppler echo displayed intrahepatic and extrahepatic PVT on post-operative Day 5. Emergent thrombectomy was performed using a Vasplyser PlusTM thrombus aspiration catheter (Johnson & Johnson K.K. Medical Company, Tokyo, Japan) via the ileocolic vein under laparotomy. The mesenteric catheter was placed at the distal point of the residual PVT. Thrombolysis and anticoagulant therapy were performed using heparin and urokinase. In the CECT performed 16 days after the additional operation, the PVT had disappeared and the portal vein was completely recanalized. The mesenteric catheter was removed on the same day and oral anticoagulant therapy was continued. At the time of writing, 14 months have passed with no recurrence of PVT. Early diagnosis of PVT enables treatment with emergent thrombectomy, thrombolysis, and anticoagulant therapy. These treatments result in the improvement of portal vein flow and the complete disappearance of PVT.

Salvage Embolization and Histologic Analysis of Gastric Cancer with Hemorrhagic Shock Using Spherical Embolic Material.

BACKGROUND: In a recent study, it was reported that transcatheter arterial embolization with spherical embolic material for life-threatening hemorrhages in various cancer patients was safe and effective. Calibrated microspheres are able to access distal regions of the target arteries, which results in the disappearance of tumor staining. However, there are few reports on the pathological behavior of EmboSpheres in gastric cancer specimens. In this case, we succeeded in salvage embolization for advanced gastric cancer with hemorrhagic shock using spherical embolic material. To our knowledge, this is the first report of a pathological evaluation of spherical embolic microspheres in a gastric cancer specimen. CASE REPORT: A 70-year-old man with scirrhous gastric cancer was admitted to our hospital for staging laparoscopy. Unfortunately, he had a sudden onset of hematemesis and melena leading to hemorrhagic shock due to bleeding from the gastric cancer. While undergoing a rapid blood transfusion, he underwent emergent embolization to achieve hemostasis. The left gastric and right gastroepiploic arteries were embolized with spherical embolic material, and the patient survived. Two days later, the patient was able to undergo gastrectomy. A large number of microspheres were observed in areas of hemorrhage. The range and median diameter of the minor axis were 177-1048 µm and 281 µm, respectively. CONCLUSIONS: Transcatheter arterial embolization using spherical embolic material could become one of safe and effective options, especially when there is no extravasation or pseudoaneurysm but only tumor staining from the clinical and pathological point of view.

Transcatheter Arterial Chemoembolization with Spherical Embolic Agent in Patients with Pulmonary or Mediastinal Metastases from Breast Cancer.

PURPOSE: To evaluate safety and feasibility of transcatheter arterial chemoembolization with superabsorbent polymer microspheres (SAP-MS) for patients with pulmonary or mediastinal metastasis from breast cancer. METHODS: Between November 2002 and January 2015, 14 patients with 29 unresectable pulmonary or mediastinal breast cancer metastases underwent transcatheter arterial chemoembolization using SAP-MS (50-100 µm) after injection of a combination of 2-4 types of anticancer drugs (eg, cisplatin [30 mg] + fluorouracil [500 mg], or epirubicin [40 mg] + mitomycin C [4 mg] + fluorouracil [500 mg]). As a primary endpoint, local tumor response and adverse events were evaluated 1 month after the first transcatheter arterial chemoembolization, according to Response Evaluation Criteria In Solid Tumors Version 1.1 and Common Terminology Criteria for Adverse Events Version 4 criteria. Transcatheter arterial chemoembolization was repeated as needed. Overall survival was analyzed as a secondary endpoint. RESULTS: Response rate was 28.6% (partial response, 4 patients; stable disease, 10 patients). Median progression rate was -12.7%. No cases of hematologic toxicity of grade 3 or higher were observed. A grade 3 maculopapular rash was observed in 1 patient. After the first transcatheter arterial chemoembolization sessions, 63 additional transcatheter arterial chemoembolization sessions were performed (average, 5.5 sessions per patient; range, 2-10 sessions). The median overall survival time after the first session was 29 months, and the 5-year survival rate was 49.5%. CONCLUSIONS: Transcatheter arterial chemoembolization with SAP-MS is a well-tolerated and feasible palliative treatment option for patients with pulmonary or mediastinal metastasis from breast cancer.

Target volume dose and clinical outcome in radiotherapy for primary marginal zone lymphoma of the ocular adnexa.

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.

Feasibility of intensity-modulated radiotherapy combined with gemcitabine and S-1 for patients with pancreatic cancer.

The aim of the present study was to establish whether intensity-modulated radiotherapy (IMRT) with concurrent gemcitabine and S-1 is a feasible treatment option for patients with locally advanced pancreatic ductal adenocarcinoma. Patients with pancreatic ductal adenocarcinoma were prospectively enrolled. An IMRT dose of 50.4 Gy in 28 fractions with concurrent gemcitabine at a dose of 600 mg/m2 and S-1 at a dose of 60 mg were administrated. Adverse events and associated dosimetric factors were assessed. Between February 2012 and January 2014, 17 patients with borderline resectable and 4 with unresectable pancreatic cancer were enrolled. None of the patients experienced grade 3 or worse nausea and vomiting. The planning target volume (≥200 vs. <200 ml) was a statistically significant predictive factor for neutrocytopenia (≥500 vs. 500/µl, P=0.02). Concurrent IMRT with gemcitabine and S-1 for patients with locally advanced pancreatic cancer is feasible, with tolerable hematological toxicities and low gastrointestinal toxicities.

Transcatheter arterial chemoembolization with spherical embolic material for locally advanced breast cancer: first report of HepaSphere™ treatment for primary breast cancer.

A 57-year-old female was diagnosed as having primary breast cancer (invasive carcinoma of no special type), which was immunohistochemically negative for oestrogen receptor, androgen receptor and human epidermal growth factor receptor Type 2. The main tumour was 54 × 35 mm in size and was located in the internal upper area of the left breast. The tumour had markedly invaded the skin and a daughter nodule was observed in the external upper area of the ipsilateral breast. An enlarged lymph node measuring 12mm in diameter was present in the axilla and an affected parasternal lymph node was also observed. A blood test showed no abnormalities and the patient was negative for tumour markers. We performed three sessions of transcatheter arterial chemoembolization with docetaxel-loaded HepaSphere™. The treatment procedure was successfully performed in all the three sessions. No adverse events higher than Grade 3 were observed. The sizes of the primary lesion and axillary lymph node decreased to 26 × 14 mm (37% reduction) and 10mm, respectively. The parasternal lymph node completely resolved. 2 months later, left total mastectomy and axillary lymph node dissection were performed. The histopathological post-therapy effect was considered to be a mild response (Grade 1a) in the breast lesion and a complete response (Grade 3) in the axillary lymph node. The mean±standard deviation of the minor axis of the vessels embolized with spherical particles was 183.0±96.5 µm. Our results indicate that transcatheter arterial chemoembolization used together with HepaSphere can be an alternative and effective therapy for locally advanced breast cancer.

[Transcatheter Arterial Chemoembolization with Super absorbent Polymer Microspheres for a Large Lung Cystic Adenocarcinoma in the Left Pulmonary Cavity].

A 57-year-old woman presented with lung adenocarcinoma and carcinomatous pleurisy in January 2013. The primary lesion had been treated with 60-Gy radiation therapy. She, however, showed a recurrence of the tumor in her pulmonary cavity. She received systemic chemotherapy for 1 year but did not show any improvement. She visited our clinic in March 2014. Her performance level was 3. Her hemoglobin level was 8.5 g/dL. The CT scan showed that the size of the cystic tumor was 200 × 144 × 143 mm. The tumor severely compressed her heart. We performed TACE using a spherical embolic agent. The microcatheter was guided through the left bronchial artery; left intercostal artery 9, 10, and 11; and the left inferior phrenic artery. The anticancer drugs selected were CDDP and 5-FU. The embolic material used was SAP-MS. After 3 therapy sessions, the CT scan showed shrinkage of the target lesion to 100 × 93 × 54 mm. Her hemoglobin level increased to 13.8 g/dL; furthermore, the severity of dyspnea decreased, and she showed a performance status of 0. TACE with SAP-MS was successfully performed for the large cystic tumor in the pulmonary cavity that metastasized from the lung cancer and was refractory to standard treatments. After the treatment, the tumor size decreased and the patient's symptoms alleviated.

[Trans-Arterial Chemoembolization Therapy for Refractory Advanced Non-Small Cell Lung Cancer with Spherical Embolic Material--A Single Case Report].

Here, we report the use of trans-arterial chemoembolization for primary lung cancer. The patient was a 56-year-old woman with refractory Stage Ⅳ non-small cell lung cancer who had been treated with repeated systemic chemotherapy. The primary lesion in the right lower lobe was 75 mm in size, with multiple lung metastases. It invaded the right main bronchus and caused severe cough. Radiotherapy was not indicated because of the size and extent of the lesion. During a period of 6 months, chemoembolization of the bilateral bronchial arteries using cisplatin 20 mg, docetaxel 20 mg, and 5-FU 250 mg with HepaSphere (super-absorbent polymer microspheres) was performed 5 times. Twenty mg of docetaxel was loaded onto 25 mg of HepaSphere. The microspheres were between 50 and 100 microns in the dry state. The endpoint of embolization was not stasis but the reduction of arterial flow. There were no serious complications during or after the procedure. Immediately after the first session, the patient's cough was significantly improved. After 5 sessions of the same treatment, the primary lesion was reduced to 48 mm and the level of CEA was reduced from 9.8 to 4.3 ng/mL. The invasion to the right main bronchus was reduced. The patient has been well without any symptoms for 9 months after initiation of trans-arterial chemoembolization.