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.

[Transarterial Chemoembolization for Unresectable Gastric Cancer in the Esophago-Gastric Junction-A Case Report].

A case of extensive esophageal stenosis and bleeding caused by advanced gastric cancer in esophago-gastric junction treated by the transarterial chemoembolization(TACE)was reported. After standard systemic chemotherapy and radiotherapy, TACE was introduced to control these symptoms. A microcatheter was successfully advanced to the left gastric artery and esophageal artery arising from the thoracic aorta. The blood supply to the lesion was confirmed by CT scan during contrast injection through the microcatheter. The drugs were 5-FU 250 mg/body, cisplatin 20 mg/body, docetaxel 20 mg/body and bevacizumab 100 mg/body. Embolic material was HepaSphereTM(50-100µm). The patient survived one and half years without dysphagia and bleeding. TACE for extensive esophageal stenosis caused by advanced gastric cancer can be a treatment option to control tumor growth and bleeding.

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.

[Optimal Clinical Strategy for Photodynamic Therapy Using Liposomal Indocyanine Green-A Case Series Study].

BACKGROUND: The biodistribution of liposomal ICG and the optimal clinical strategy for PDT using liposomal ICG is unclear because of the lack of clinical evidences. PURPOSE: This case-series study aimed to evaluate the biodistribution of liposomal ICG in patients with breast cancer undergoing PDT. METHOD AND RESULT: Four patients with breast cancer underwent PDT with liposomal ICG in addition to a transcatheter arterial chemoembolization(TACE)from August 2020 to October 2020. Patients were administered 300 mg liposomal ICG(180 mg intravenously and 120 mg intratumorally via the feeding artery) 24 hours before PDT during a TACE procedure. We used near-infrared fluorescence(NIR)imaging system(LIGHTVISION®; Shimadzu Corporation)to detect the biodistribution of liposomal ICG. The peak intratumoral liposomal ICG uptake was shown 24 hours after liposomal ICG administration in 3 patients. Only 1 patient had peak uptake at 6 hours, with no uptake at 24 hours. CONCLUSION: NIR-imaging system may be and adjuvant in evaluation of liposomal ICG biodistribution in patients with breast cancer and assisting in the decision-making for the use of PDT with liposomal ICG.

[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.

[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.

[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 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.

[Introduction of Hyperthermia Therapy with Low Dose Systemic Chemotherapy and Hepatic Transarterial Chemo-Embolization for a Case of Advanced Prostatic Cancer].

The case of a 78-year-old man with hormone-independent locally advanced prostatic cancer with liver metastases is reported. Standard systemic chemotherapy was not administered due to his poor general condition. At the initial consultation, rapidly growing liver metastases, multiple lymph node metastases, and extensive locally advanced prostatic lesions were found. Transcatheter arterial chemoembolization, low dose systemic chemotherapy, and thermotherapy were administered. After introduction of this combination therapy, marked regression of all of the lesions, including the liver metastases, lymph node metastases, and pelvic extension was observed. The patient's condition and prognosis were markedly improved without serious complications.

[A Case of Successful Drug-Eluting Microsphere Transcatheter Arterial Embolization for Hepatocellular Carcinoma with Associated Tumor Thrombus in the Inferior Vena Cava and Right Atrium].

Hepatocellular carcinoma(HCC)with severe vascular invasion has a dismal prognosis, and there is no well-established effective therapy. We report an 84-year-old man who benefited from multiple transcatheter arterial chemoembolization (TACE)treatments for advanced HCC with severe vascular invasion. Initial CT revealed a recurrent, poorly differentiated HCC with tumor thrombus in the inferior vena cava(IVC)and right atrium(Vv3). Two cycles of TACE with 5-FU, DOC, MMC, and superabsorbent polymer microspheres(SAP-MS)with BV resulted in considerable reduction of the tumor thrombus. Tumor markers(PIVKA- / / II)showed remarkable improvement(from 3,803 mAU/mL to 673 mAU/mL). The patient has been alive for 25 months following the appearance of tumor thrombus in the IVC. This case suggests that, in patients with tumor thrombi due to hepatocellular carcinoma, thrombus control and long-term survival are achievable with TACE.

[Trans-Arterial Chemoembolization Therapy for Giant Cholangiocellular Carcinoma - A Single Case Report].

Here, we report a case of cholangiocellular carcinoma that was successfully treated with chemotherapy using a selective intra-arterial infusion technique. A 65-year-old man presented to our hospital to obtain a second opinion regarding his disease. The patient was diagnosed with cholangiocellular carcinoma. The giant tumor was located in the porta hepatis. Some small nodules that were considered to be metastatic lesions were also observed in the surroundingarea. The tumor was judged by the primary physician to be too large for surgical treatment. Consequently, it was decided to treat the patient with trans-arterial chemoembolization(TACE)by selectingintra -arterial infusion of 5-FU, epirubicin(EPI), and mitomycin C prior to EPI-loaded HepaSphere(super-absorbent polymer microsphere)embolization, combined with concurrent systemic gemcitabine chemotherapy. After 5 sessions of the above treatment, the primary lesion reduced dramatically in size. In addition, the levels of CEA and CA19-9 decreased from 34.2 to 2.6 ng/mL and 1,540 to 149 U/mL, respectively. Although the patient's initial life expectancy was only 3 to 6 months, his life expectancy was extended to as longas 26 months followingthe initiation of TACE. This case suggests that treatment with TACE together with systemic chemotherapy can be a powerful therapeutic option for patients with inoperable cholangiocellular carcinoma.

[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.

[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.

Local control and prognostic significance of transarterial treatment for limited recurrence of ovarian cancer as third-line and beyond therapy.

BACKGROUND: We aimed to retrospectively evaluate the safety and efficacy of transarterial treatment for the recurrence of ovarian cancer, limited to one or two gross regions, in a palliative setting as third-line and beyond therapy. METHODS: Twenty-six consecutive patients were enrolled to undergo transarterial treatment of target lesions that were life-threatening or influenced their quality of life. Transarterial infusion via each feeding artery using 20-40 mg cisplatin and 20-40 mg docetaxel per patient was repeated every 4-6 weeks. Superabsorbent polymer microspheres were added for embolization after drug infusion, especially in hepatic or pelvic treatments. Univariate and multivariate Cox's proportional hazards models were used to assess the correlations between overall survival and individual parameters. RESULTS: A total of 63 feeding arteries (median 2 per patient; range 1-5) were treated for 36 target sites (liver, 12; pelvis, 8; abdominal cavity, 7; lymph node, 3; other, 6) at the initial treatment. Of the 128 total sessions, the only grade 3/4 toxicity was neutropenia (3.8 %). The target lesion response rate by RECIST ver.1.1 was 50.0 % (11.5 % complete response; 38.5 % partial response). After a median follow-up of 30 months, the median overall survival was 16 months. Among 10 tumor-associated symptomatic patients, 7 showed symptom improvement. Multivariate analyses shows that the only independent prognostic factor was target lesion response (hazard ratio 18.7; 95 % CI 1.9-183.4; p = 0.01). CONCLUSIONS: Transarterial treatment for ovarian cancer achieves a high local response and good symptom control, and significantly contributes to survival for patients with local control after multiple relapses.

Accelerated evolution of fetuin family proteins in Protobothrops flavoviridis (habu snake) serum and the discovery of an L1-like genomic element in the intronic sequence of a fetuin-encoding gene.

Habu serum factor (HSF) and HSF-like protein (HLP) are fetuin family proteins isolated from Protobothrops flavoviridis (habu snake) serum with different physiological activities. A comparison of their cDNAs and intronic sequences revealed that nucleotide substitutions were primarily in protein-coding regions, and the substitution patterns indicated accelerated evolution of these proteins. Genomic DNA fragment analysis, including intron 1, revealed a 6.6-kb insertion homologous to the full-length mammalian LINE1 (L1) retrotransposable element (PfL1) only in the HLP gene. This segment retains an open reading frame (ORF) that encodes a reverse transcriptase (RT)-like protein (PfRT). We further found that a large number of homologous segments have dispersed in the habu snake genome, although we could not determine the enzymatic activities of their products. Moreover, an analysis of habu snake liver RNA indicated active transcription of the PfRT genes, suggesting that high levels of RT activity in this snake have driven the evolution of unique phenotypes of venom enzymes and serum inhibitors of them.

[Effect of transarterial chemoembolization for recurrent desmoid tumor - a case report].

Desmoid fibromatosis is classified as a benign soft tissue tumor regardless of its local invasive behavior and its, local recurrence rate is 57-85% after local resection. A 19 y/o male patient with post-operative recurrence of a desmoid tumor in the shoulder was initially treated by arterial embolization; however, no improvement of symptoms was obtained. As second-line treatment, 20 mg of epirubicin, 50 mg of cisplatin and 250 mg of 5-FU were infused to tumor-related arteries and embolization was performed with a super absorbent polymer microsphere. After a single session of treatment, reduction of tumor size and improvement of symptoms were achieved. The same treatment was repeated three times without major complications. Considerable reduction of tumor was obtained after treatment. Chemo-embolization should be considered for the postoperative recurrence of desmoid fibromatosis, in order to prevent loss of function and maintain a high QOL for the patient.

In vivo evaluation of cisplatin-loaded superabsorbent polymer microspheres for use in chemoembolization of VX2 liver tumors.

PURPOSE: To investigate the pharmacokinetics and efficacy of chemoembolization with a cisplatin-loaded superabsorbent polymer (SAP) suspension in a rabbit model with transplanted liver VX2 tumors. MATERIALS AND METHODS: VX2 tumors were implanted into the left lobe of the liver in eight rabbits. Embolization of the proper hepatic artery was performed with cisplatin-loaded or unloaded SAP. In the cisplatin-loaded SAP group (n = 4), 5 mg of SAP (106-150 µm) loading 2.35 mg of cisplatin and 0.5 mL of ionic contrast material (ioxaglic acid 320 mgI/mL) was injected into the proper hepatic artery. In the control group (hepatic arterial infusion [HAI] + SAP; n = 4), 5 mg of SAP loading 0.5 mL of ioxaglic acid alone was injected after a bolus infusion of an equivalent amount of cisplatin. Sequential change of the plasma platinum concentration within the first 24 hours was measured. Blood sampling and histopathologic examination were performed at 1-week follow-up. Magnetic resonance (MR) images were used to calculate the growth rate of the VX2 tumor. RESULTS: All animals underwent successful embolization. Both total and free plasma platinum mean concentrations within the first 24 hours remained lower in the cisplatin-loaded SAP group, although without statistical significance (P > .05). The mean tumor growth rate was significantly lower in the cisplatin-loaded SAP group than the control group (20% vs 116%; P = .049). Histopathologic examination revealed coagulative necrosis to nontumorous liver parenchyma in two rabbits in the cisplatin-loaded SAP group, although no deaths occurred. CONCLUSIONS: These results suggested that chemoembolization with cisplatin-loaded SAP was a safe and tolerable treatment and was more effective in suppressing the tumor growth.

Current status of embolic agents for liver tumor embolization.

Gelatin sponge and polyvinyl alcohol particles have been the most popular particulate embolic agents for transarterial chemoembolization (TACE) of liver tumors. Over the last decade, calibrated microspheres have been introduced and increasingly used in liver tumor embolization in Western countries. In addition, drug-eluting beads (DEB) have been introduced for sustained local drug release. Such long-awaited spherical embolic agents will be introduced in Japan in the near future. The advantages of these microspheres are that particles are uniform in size and shape, and easy to inject through a microcatheter. They can travel distally to vessels corresponding to the particle size; in other words, the occlusion level can be predicted according to the particle size chosen. Thus, new bland microspheres and DEB may bring a significant advancement to embolization for primary liver tumors as well as hepatic metastases from various cancers. However, at this point, the published data suggests that both conventional TACE and DEB-TACE are equally effective for treatment of unresectable hepatocellular carcinoma, when patients are carefully selected. Therefore, indication, patient selection, and embolization techniques will be essential in order to individually adapt newer embolic agents based on oncological, anatomical and technical considerations.

Successful control of a large intrahepatic cholangiocarcinoma treated by transarterial chemo-embolization; a single case report.

Intrahepatic cholangiocarcinoma is hardly diagnosed in early stages as the symptoms are non-specific. Due to an advanced stages at the time of first diagnosis, the therapeutic options for patients with unresectable cholangiocarcinoma are mostly limited to systemic chemotherapy or radiotherapy, but good local control or preferable prognostic effects are hardly obtained. The transarterial chemoembolization had not been a standard of care because of hepatic functional damages caused by lipiodol and gelatin sponge. A newly developed spherical embolic material causes limited hepatic damages might be an option for these patients. It makes it possible to repeat the procedure in a short period. Eventually, better prognosis can be expected using a spherical embolic material. We report a case of a 15 cm locally advanced intrahepatic cholangiocarcinoma treated by chemoembolization using a drug-eluting spherical embolic material and achieved good local tumor control without liver damage. The patient survived longer than 4 years without additional or concomitant treatments.

Transarterial Treatment of Lung Cancer.

PURPOSE: The treatment efficacy of the transarterial approach to lung cancer is evaluated. MATERIALS AND METHODS: A total of 98 patients with advanced lung cancer or recurrent lung cancer after the standard therapies were enrolled retrospectively. The bronchial arteries and mediastinal branches from the subclavian artery were selected by a microcatheter. Immediately after the selective arterial infusion of anti-neoplastic agents, embolization with a spherical embolic material was carried out. Local tumor effects and overall survival were evaluated. RESULT: The mean reduction rate was 17.9%, with 24.2% for partial remission and with 2.1% for progression disease. The rate of stable disease was 72.6%. The response rate was 25.3%, and the disease control rate was 97.9%. The median survival time (MST) was 11.4 months, the 1-year survival rate was 45.2%, and the 2-year survival rate was 35.6%. Although it is insignificant, the MST for 51 adenocarcinomas was higher than that of 29 squamous cell carcinomas (18.6 months and 9.4 months, respectively). The local extension of tumors related to a better prognosis, though it was not significant. Lymph node metastases and distant metastases were poor prognostic factors. No major complications nor treatment-related mortalities were found in this study. CONCLUSION: The transarterial treatment for lung cancer should be considered as a treatment option when the other treatments were not indicated both in initial cases and in recurrent cases.