Intra-arterial EmboCept S® and DC Bead® effectively inhibit tumor growth of colorectal rat liver metastases.

BACKGROUND: Intra-arterial therapy with embolics is established for the treatment of malignancies of the liver. However, there are no studies comparing the different effects of various embolics used in clinical practice. Herein, we analyzed the effect of 3 different embolics on tumor growth in a rat model of colorectal liver metastases. METHODS: Eight days after subcapsular implantation of 5 × 105 colorectal cancer cells (CC531) in the left liver lobe of WAG/Rij rats were randomized into 4 groups (n = 8) and underwent intra-arterial hepatic therapy. Animals received either EmboCept S®, DC Bead® or Lipiodol® Ultra-Fluid. Animals of the control group received a comparable amount of saline. Tumor growth was measured on day 8 and 11 using a three-dimensional 40 MHz ultrasound device. On day 11 tumor and liver tissue were removed for histological and immunohistochemical analyses. RESULTS: On day 11 animals of the control group showed a tumor growth of ~ 60% compared to day 8. Application of Lipiodol Ultra-Fluid® did not significantly influence tumor growth (~ 40%). In contrast, treatment with EmboCept S® or DC Bead® completely inhibited tumor growth. Of interest, application of EmboCept S® did not only completely inhibit tumor growth but even decreased tumor size. Immunohistochemical analysis showed a significant increase of necrotic areas within the tumors after application of EmboCept S® and DC Bead® compared to Lipiodol® Ultra-Fluid. CONCLUSION: The present study demonstrates that an intra-arterial therapy with EmboCept S® and DC Bead®, but not Lipiodol® Ultra-Fluid, results in a complete inhibition of rat colorectal liver metastatic growth.

Long-term follow-up of transarterial balloon-assisted Onyx embolization for endovascular treatment of dural arteriovenous fistulas: A single-institution case series and literature review.

OBJECTIVE: Dural arteriovenous fistulas (DAVFs)-specifically, symptomatic DAVFs with cortical venous reflux-are aggressive lesions with a poor prognosis. Intra-arterial endovascular closure is considered the optional treatment for DAVFs and is currently performed at several international centers. However, long-term outcomes remain unknown. This study investigated the long-term efficacy and safety of transarterial balloon-assisted Onyx embolization in the treatment of DAVFs. METHODS: A total of 14 consecutive patients who underwent endovascular treatment for DAVFs were treated by balloon-assisted Onyx embolization. Additionally, we retrospectively reviewed all cases reported in the literature and compared the outcomes of patients treated with single- vs dual-lumen microcatheters. RESULTS: The patients at our institution were followed-up for 114.57 ± 33.52 months. Embolization was performed by balloon-assisted Onyx injection via a single feeding artery. Complete occlusion was achieved in 13 cases and partial occlusion in 1 case. At the final follow-up, all patients were functionally independent (Modified Rankin Scale score of 0-2), with no recurrence. In our review of 70 published cases of DAVFs that underwent endovascular treatment by balloon-assisted Onyx embolization, single- and dual-lumen balloon catheters were used in 33 and 37 patients, respectively. In the former group, there was complete or near-complete occlusion in 32 cases and partial occlusion in 1 case; and in the latter, there was complete or near-complete occlusion in 35 cases and partial occlusion in 2 cases. There were no deaths following endovascular treatment. CONCLUSION: Measurable and durable outcomes can be achieved by endovascular treatment of DAVFs with the transarterial balloon-assisted Onyx embolization technique, especially in cases with small, distal, and circuitous feeding arteries.

Use of N-butyl cyanoacrylate in implantation of a port-catheter system for hepatic arterial infusion chemotherapy with the fixed-catheter-tip method: is it necessary?

OBJECTIVE: The purpose of our study was to evaluate the usefulness of N-butyl cyanoacrylate (NBCA) in addition to microcoils in the percutaneous implantation of a port-catheter system for repeated hepatic arterial infusion chemotherapy with the fixed-catheter-tip method. MATERIALS AND METHODS: We retrospectively studied 166 consecutive patients with unresectable advanced liver cancer for whom a port-catheter system was percutaneously implanted with its tip fixed at the gastroduodenal artery with microcoils. In 107 patients, NBCA was also used for catheter tip fixation. We compared this group with a control cohort of 59 patients who did not receive NBCA. Outcomes, including rate of success in implantation, details of embolic agents for fixation, and occurrence of complications related to catheter placement that would prohibit continuation of chemotherapy if not corrected, were compared. RESULTS: In all, port-catheter placement was successful. However, 38 complications occurred in 32 patients. Catheter dislocation occurred in nine. Hepatic artery obstruction or severe stenosis was seen in 10. Recanalization of a once-embolized gastroduodenal artery was found in two patients. The rate of dislocation did not differ significantly between patients in whom NBCA was and those in whom it was not used. However, hepatic artery obstruction appeared at a significantly higher rate, and recanalization of a gastroduodenal artery at a significantly lower rate, in patients in whom the catheter tip was fixed with NBCA. CONCLUSION: The use of NBCA correlated with a higher rate of hepatic artery obstruction. The use of NBCA should not always be required in port-catheter implantation with the fixed-catheter-tip method.

A two-scale approach for CFD modeling of endovascular Chemofilter device.

Two-scale CFD modeling is used to design and optimize a novel endovascular filtration device for removing toxins from flowing blood. The Chemofilter is temporarily deployed in the venous side of a tumor during the intra-arterial chemotherapy in order to filter excessive chemotherapy drugs such as Doxorubicin from the blood stream. The device chemically binds selective drugs to its surface thus filtering them from blood, after they have had the effect on the tumor and before they reach the heart and other organs. The Chemofilter consists of a porous membrane made of microscale architected materials and is installed on a structure similar to an embolic protection device. Simulations resolving the microscale structure of the device were carried out to determine the permeability of the microcell membrane. The resulting permeability coefficients were then used for macroscale simulations of the flow through the device modeled as a porous material. The microscale simulations indicate that greater number of microcell layers and smaller microcell size result in increased pressure drop across the membrane, while providing larger surface area for drug binding. In the macroscale simulations, the study of idealized prototypes show that the pressure drop can be reduced by increasing the membrane's tip angle and by decreasing the number of membrane's sectors. Such design, however, can conversely affect the overall drug binding. By decreasing the concentration of toxins in the cardiovascular system, the drug dosage can be increased while side effects are reduced, thus improving the effectiveness of treatment.

Combined therapy after superselective arterial cisplatin infusion to treat maxillary squamous cell carcinoma.

OBJECTIVE: We sought to assess the efficacy of combined therapy after superselective arterial cisplatin infusion (SACI) therapy to treat the maxillary squamous cell carcinoma. STUDY DESIGN: We conducted a retrospective chart review of 50 patients. After completion of two courses of SACI, 25 of the patients were successively treated by concurrent SACI and radiotherapy (AR), while the other 25 patients were treated by surgery with postoperative radiotherapy (ASR). RESULTS: Patients with surgery (ASR) had an 88% local control rate with 75% disease-free survival rate at 60 months by Kaplan-Meier analysis, compared with 62% disease-free survival rate for patients with AR treatment. A particularly good outcome was obtained in T4 cases of the ASR group (n=8) whose 5-year survival rate was 87% and local control rate was 100%. CONCLUSION/SIGNIFICANCE: Combined SACI therapy is very effective for the treatment of maxillary squamous cell carcinomas and contributes to the improving prognoses of patients and organ preservation rates.

Combination of retrograde superselective intra-arterial chemotherapy and Seldinger method in locally advanced oral cancer.

The nonsurgical strategies for locally advanced oral cancer are desirable. Superselective intra-arterial infusion with radiotherapy was utilized for this purpose, and there are two types of superselective intra-arterial infusion methods: The Seldinger method and the retrograde superselective intra-arterial chemotherapy (HFT method). In one case, the HFT method was applied to locally advanced tongue cancer, and the Seldinger method was used for additional administration of cisplatin (CDDP) to compensate for a lack of drug flow in the HFT method. In another case, the HFT method was applied to locally advanced lower gingival cancer. The Seldinger method was applied to metastatic lymph nodes. In both cases, additional administration of CDDP using the Seldinger method resulted in a complete response. The combination of the HFT and Seldinger methods was useful to eradicate locally advanced oral cancer because each method compensated for the defects of the other.

An experimental study of embolic effect according to infusion rate and concentration of suspension in transarterial particulate embolization.

RATIONALE AND OBJECTIVES: The authors evaluate the embolic effect according to infusion rate and concentration of particulate suspension, focusing on arterial occlusion level. METHODS: The renal arteries of 14 rabbits were embolized with 150 to 250 microns polyvinyl alcohol (PVA) particles, divided into four groups according to two different infusion rates (1 mg/second and 0.1 mg/second) and two different concentrations of suspension (10 mg/mL and 2.5 mg/mL). Arteriograms obtained immediately and a week after embolization were assessed for occlusion level. For the nephrograms obtained a week after embolization, the opacifying areas were graded from 0 to 4. Median coronal sections of each kidney specimen were investigated for the presence of peripheral infarct grossly and for the presence of PVA particles in the small artery microscopically. RESULTS: Arteriograms showed various occlusion levels. Using a 0 to 4 grading system, the opacifying area of the nephrogram obtained 1 week after embolization was noted to be smaller in the low infusion rate group (P < 0.05). In gross and microscopic pathologic examination, the number of cases with peripheral infarct or PVA particles in the small artery (< 300 microns) was greater in the group with the low infusion rate and low concentration (P < 0.05). CONCLUSIONS: In transarterial particulate embolization, slower infusion of more diluted suspension provides for a more distal arterial occlusion.

[A method to retain subcutaneously the catheter end connected to a new silicone reservoir in intraarterial infusion chemotherapy].

A method to retain subcutaneously the catheter end connected to a new silicone reservoir was developed in intraarterial infusion chemotherapy and applied to 12 patients. Its advantages were discussed. The method can be performed with only minor invasion; in addition, the retained catheter and reservoir needs no aseptic care. Accordingly, it liberates patients from restrictions in the daily life thus far experienced in the conventional method. The intraarterial infusion therapy can be done more easily and without hospitalization by this method. Thus, the method is considered to be quite beneficial in taking care of advanced cancer patients.

[Intra-arterial infusion chemotherapy using a subcutaneously implanted silicone reservoir--with special reference to the method].

Sixty patients with advanced cancers were treated with intraarterial infusion chemotherapy using a subcutaneously implanted silicone reservoir. Forty-nine patients were catheterized from a branch of the left subclavian artery. The results were as follows. (1) In spite of some technical difficulties, catheterization from a branch of the left subclavian artery was minimally invasive, and catheter trouble using this route was less frequent than that occurring when the profound femoral arterial route was employed. (2) Implantation of the catheter end using a silicone reservoir liberated the patients from restrictions in their daily lives, and with this method, intraarterial infusion chemotherapy could be carried out easily when required without hospitalization. We conclude that this procedure is a beneficial method of intraarterial infusion chemotherapy for patients with advanced cancers.

[Intra-arterial infusion chemotherapy using a subcutaneously implanted silicone reservoir--with reference to the chemotherapy protocol].

Sixty patients with advanced cancers were treated with intraarterial infusion chemotherapy using a subcutaneously implanted silicone reservoir. Forty-five patients received a low dose-intermittent intraarterial infusion chemotherapy employing either combination MFC (MMC 4 mg, 5-FU 500 mg, Ara-C 40 mg) at intervals of two weeks or MMC 4 mg weekly. The results were as follows. (1) Among 30 cases, where objective evaluation of the initial response was possible, partial responses (PR) were observed in 15 cases (50%). (2) No severe complication was observed using this protocol. Only one case out of the 45 needed to discontinue the medication because of bone marrow suppression. (3) Among 28 cases, where follow-up data were available, the average hospital-free interval was 207 days. The average ratio of hospital-free interval to survival period was 56.4%. The results indicate that our method is beneficial as a maintenance chemotherapy for patients with advanced cancers, because it is effective, safer and improves the quality of life.

[A case of massive hepatoma which responded to SMANCS/Lipiodol regimen with intra-arterial infusion].

Transcatheter arterial chemotherapy (SMANCS/lipiodol) was applied to massive hepatoma, which had a high AFP 213,000 ng/ml, A-P shunt, tumor thrombosis and metastatic lung cancer. After 3 months, the AFP value reduced to 18 ng/ml, massive hepatoma and the A-P shunt disappeared, but AFP-negative nodular hepatoma recurred around initial hepatoma. Each time, we injected SMANCS/lipiodol to the recurring hepatoma. The therapy in the initial stage was not so effective. The portal vein was not observed in the initial stage, but appeared after the second dosage. Metastatic lung cancer was declining in the initial dosage and 23 months later disappeared after the third dosage. The massive hepatoma occupied entirely the rt. lobe of the liver. The patient lived for 4 years, had total admission periods of 190 days and could return to life in society. In this case, we considered that transcatheter arterial chemotherapy (SMANCS/lipiodol) had remarkable effects.

Continuous intra-arterial chemotherapy for downstaging locally advanced oral commissure carcinoma.

BACKGROUND: The purpose of this study was to assess the usefulness, safety, and efficacy of intra-arterial (IA) infusion chemotherapy for patients with locally advanced oral commissure cancer. METHODS: Twenty-one patients with stages III and IV squamous cell carcinoma involving the mouth angle were recruited. Methotrexate (MTX; 50 mg/day) was continuously infused into the external carotid artery for a mean period of 8 days, followed by weekly IA bolus of 25 mg MTX for a mean period of 10 weeks. RESULTS: Thirteen patients (62%) achieved a complete response (CR) and 7 patients (33%) had a partial response (PR). At a median follow-up of 69 months, the estimated 1-year, 3-year, and 5-year survival rates of the patients with CR versus PR were 100% versus 57%, 92% versus 43%, and 80% versus 43%, respectively. CONCLUSION: Our data demonstrate that continuous IA chemotherapy could achieve a competitive acceptable survival rate and improved locoregional control of advanced oral commissure cancer.

A newly developed double lumen microballoon catheter with a side hole: initial experience of intraarterial infusion chemotherapy and/or embolization.

PURPOSE: To introduce a newly developed double lumen microballoon catheter with a side hole for intraarterial infusion chemotherapy and/or embolization. METHODS AND MATERIALS: Seven patients with malignant tumors, for whom superselective catheterization was considered difficult or had failed, underwent intraarterial infusion chemotherapy and/or embolization with the 3.3-Fr microballoon catheter. The catheter has a double lumen and a side hole to facilitate infusion from the proximal end of the balloon. The balloon was placed on the distal side of the target artery branching site. Inflation of the balloon and occlusion of the main lumen with the tip of the occlusion device allowed for intraarterial infusion chemotherapy and/or embolization of the target artery via the side hole. RESULTS: Successful intraarterial infusion chemotherapy and/or embolization with the microballoon catheter was performed in all patients with no complications. CONCLUSIONS: The newly developed microballoon catheter achieves intraarterial infusion chemotherapy and/or embolization without the need for superselective catheterization.

Significant improvement in superselective intra-arterial chemotherapy for oral cancer by using indocyanine green fluorescence.

BACKGROUND: Recent advances in indocyanine green (ICG) fluorescence imaging have enabled the visualization of the blood supply to tissues. For advanced head and neck cancer, intra-arterial chemotherapy has been applied for organ preservation and improvement of the prognosis. To identify the tumor-feeding artery, through which the intra-arterial chemotherapy should be administered, CT angiography has been shown to be useful. However, the precise evaluation for oral cancer patients depends on the oral environment, that is, whether they have been treated with dental metal. OBJECTIVES: To assess the feasibility of the ICG fluorescence technique during intra-arterial chemotherapy for advanced oral cancer. MATERIAL AND METHOD: Twenty-five patients with oral cancer who were treated by intra-arterial chemotherapy were included in this study. Conventional CT angiography followed by 5mg of ICG injection was performed to confirm the areas in which the drug had dispersed. Intra-arterial chemotherapy was administered at 75 mg/m(2) of CDDP. Additional information about the arteries feeding the tumors provided by ICG was evaluated. RESULTS: Out of 25 cases, in 15 (56%) the blood supply to the cancer was clearly detected by CT angiography. Using the infrared ICG evaluation, the blood supply to the tumor was confirmed easily in all cases. The information obtained from fluorescence imaging was helpful for making decisions concerning the administration of chemo-agents for oral cancers. CONCLUSION: ICG fluorescence imaging during intra-arterial chemotherapy compensated for the deficiencies of CT angiography, especially for oral cancer. ICG fluorescence provided us clearer and more useful information about the feeders to tumors.

Glioblastoma treatment: bypassing the toxicity of platinum compounds by using liposomal formulation and increasing treatment efficiency with concomitant radiotherapy.

PURPOSE: Treatments of glioblastoma with cisplatin or oxaliplatin only marginally improve the overall survival of patients and cause important side effects. To prevent adverse effects, improve delivery, and optimize the tumor response to treatment in combination with radiotherapy, a potential approach consists of incorporating the platinum agent in a liposome. METHODS AND MATERIALS: In this study, cisplatin, oxaliplatin, carboplatin, Lipoplatin (the liposomal formulation of cisplatin), and Lipoxal (the liposomal formulation of oxaliplatin) were tested on F98 glioma orthotopically implanted in Fischer rats. The platinum compounds were administered by intracarotid infusion and were assessed for the ability to reduce toxicity, improve cancer cell uptake, and increase survival of animals when combined or not combined with radiotherapy. RESULTS: The tumor uptake was 2.4-fold more important for Lipoxal than the liposome-free oxaliplatin. Lipoxal also improved the specificity of oxaliplatin as shown by a higher ratio of tumor to right hemisphere uptake. Surprisingly, Lipoplatin led to lower tumor uptake compared with cisplatin. However, Lipoplatin had the advantage of largely reducing the toxicity of cisplatin and allowed us to capitalize on the anticancer activity of this agent. CONCLUSION: Among the five platinum compounds tested, carboplatin showed the best increase in survival when combined with radiation for treatment of glioma implanted in Fischer rats.

Organ preservation with daily concurrent chemoradiotherapy using superselective intra-arterial infusion via a superficial temporal artery for T3 and T4 head and neck cancer.

PURPOSE: To evaluate the therapeutic results and rate of organ preservation in patients with advanced head and neck cancer treated with superselective intra-arterial chemotherapy via a superficial temporal artery and daily concurrent radiotherapy. METHODS AND MATERIALS: Between April 2002 and March 2006, 30 patients with T3 or T4a squamous cell carcinoma of the head and neck underwent intra-arterial chemoradiotherapy. Treatment consisted of superselective intra-arterial infusions (docetaxel, total 60 mg/m(2); cisplatin, total 150 mg/m(2)) and daily concurrent radiotherapy (total, 60 Gy) for 6 weeks. RESULTS: The median follow-up for all patients was 46.2 months (range, 10-90 months). The median follow-up for living patients was 49.7 months (range, 36-90 months). After intra-arterial chemoradiotherapy was administered, primary site complete response was achieved in 30 (100%) of 30 cases. Seven patients (23.3%) died. Using the Kaplan-Meier method, 1-year, 3-year, and 5-year survival rates were 96.7%, 83.1%, and 70.2%, respectively, while 1-year, 3-year, and 5-year local control rates were 83.3%, 79.7%, and 73.0%, respectively. Grade 3 or 4 mucositis occurred in 20 cases (66.7%). Grade 3 toxicities included dysphagia in 20 cases (66.7%), dermatitis in 6 cases (20%), nausea/vomiting in 2 cases (6.7%), and neutropenia and thrombocytopenia in 1 case (3.3%). No osteoradionecrosis of mandible and maxillary bones developed during follow-up. CONCLUSIONS: Intra-arterial chemoradiotherapy using a superficial temporal artery provided good overall survival and local control rates. This combination chemoradiotherapy approach can preserve organs and minimize functional disturbance, thus contributing to patients' quality of life.

Modification of the catheterization procedure for the totally implantable infusion pump.

The totally implantable infusion pump is a new and expensive device. Once this pump is unpacked and is in contact with a patient, it is impossible to have it resterilized. For this reason, we suggest the use of a separate catheter for catheterization. Once the catheter is successfully placed in the appropriate artery, then the pump can be unpacked and attached to this catheter. If catheterization proves impossible, the pump is still sterile and can be used for the next patient.

Mechanisms of delivery and local drug delivery technologies.

Therapy of atherosclerotic vascular disease and neointimal hyperplasia after percutaneous interventions remain enigmatic. Despite new interventional devices, we have not altered the underlying pathological process. New devices are under development that offer the opportunity to deliver high concentrations of therapeutic agents directly to the diseased segment. The devices fall into three major mechanisms of delivery (1) diffusion, (2) infusion under pressure and (3) mechanical delivery. Diffusion catheters are atraumatic but require prolonged exposures in excess of 20 min while the pressurized infusion and mechanical catheters are more traumatic. Additionally, each system will need to be characterized with respect to efficiency of delivery with each agent used. The clinical opportunity for site-specific treatment of vascular disease is rapidly approaching. In the near future we will be able to open a narrowed vessel and also apply some agent into the lesion to facilitate healing.

Using n-butyl cyanoacrylate and the fixed-catheter-tip technique in percutaneous implantation of a port-catheter system in patients undergoing repeated hepatic arterial chemotherapy.

OBJECTIVE: The purpose of our study was to evaluate the usefulness of adding n-butyl cyanoacrylate to microcoils to fix the catheter tip in percutaneous implantation of a port-catheter system for hepatic arterial-infusion chemotherapy. SUBJECTS AND METHODS: Ninety-three patients (64 men and 29 women; age range, 38-83 years; mean age, 62.2 years) with unresectable advanced liver cancer underwent percutaneous implantation of a port-catheter system with the catheter tip fixed at the gastroduodenal artery with microcoils and a mixture of n-butyl cyanoacrylate and iodized oil. The rates of successful implantation and complications closely associated with this technique and management of the complications were reviewed. RESULTS: Percutaneous port-catheter placement was successfully performed in all patients. However, in eight patients, complications occurred: hepatic arterial obstruction (n = 5, 5.4%); catheter dislocation (n = 2, 2.2%); recanalization of the gastroduodenal artery (n = 1, 1.1%); or movement of n-butyl cyanoacrylate (n = 1, 1.1%). In five of the eight patients with complications, hepatic arterial-infusion chemotherapy was continued either after observation of the patient to ensure that stability had been established or after treatment using comparatively easy interventional techniques. In three (3.2%) of the 93 patients, planned hepatic arterial-infusion chemotherapy could not be performed because of complications associated with the technique. CONCLUSION: Fixation of the catheter tip in the gastroduodenal artery using a combination of microcoils and a mixture of n-butyl cyanoacrylate and iodized oil is a useful and safe technique in percutaneous port-catheter placement for repeated hepatic arterial infusion chemotherapy.