Chemoembolization Using Alkylcyanoacrylates

HCC is the most common liver tumor, with heterogeneity in the tumor behavior and the underlying liver disease. Recent combinations such as cisplatin, interferon, Adriamycin, and 5-FU are extremely toxic and yield response rates of only 20%, with no survival advantage compared to supportive care alone.184 Higher concentrations of cancer chemotherapeutic agents can be delivered directly to the HCC via the hepatic arterial route. Considering that this route is the major vascular supply of these tumors, an even larger number of papers have reported the experience of hepatic artery chemotherapy or hepatic artery chemoembolization (TACE) with single agents, or with a dizzying combination of agents, and at doses not replicated by any two institutions. Loewe et al.185 evaluated the potential of transarterial permanent embolization with the use of a mixture of cyanoacrylate and lipiodol for the treatment of unresectable primary HCC. Loewe et al.186 used NBCA for hepatic artery embolization for the treatment of small-bowel neuroendocrine metastases to the liver. The results revealed that the permanent embolization of hepatic arteries as part of a multimodality treatment protocol is beneficial in long-term follow-up for patients with metastasized small-bowel neuroendocrine tumors. The use of cyanoacrylate is safe and effective as an embolic agent.

Transarterial embolization (TAE) with the use of microspheres and Lipiodol and cyanoacrylate for unresectable HCC is a feasible treatment modality. A retrospective analysis of 46 patients with histologically confirmed HCC was made who were treated with TAE of the hepatic arteries.187 To induce permanent embolization, the microspheres (Embosphere; 100-700 mm) and a mixture of ethiodized oil (Lipiodol Ultrafluide) with cyanoacrylate (Glubran) was administrated. No patient died during embolization or within the first 24 h. Severe procedure-related complications were observed in 2 patients. At the time of the analysis, 38 of 46 patients were alive. The 180-, 360-, 520, and 700-day cumulative survival rates for the total study population were 80.6%, 70.7%, 70.7%, and 47.1%, respectively, with a median survival of 666 days.

A procedure for effective and promising preoperative embolization of carotid body tumors was reported by Harman et al.188 Ultrasound-guided direct percutaneous injection of n-butyl cyanoa-crylate was given, and angiographic road map assistance was used for protection of parent arteries during the injection. After embolization, complete devascularization of the tumor was achieved without complications. The tumor was removed surgically with minimal blood loss. Transcatheter arterial embolization (TAE) of splanchnic arterial branches to allow continuous application of repeat hepatic arterial infusion chemotherapy (HAIC) was assessed.189 One hundred and twenty-eight patients with unresectable advanced liver cancer were implanted with a percutaneous port catheter system and TAE of splanchnic arteries with coils and/or NBCA. The recanalization rate between coil-embolized and NBCA- or NBCA-coil-embolized arteries, and frequency of hetero-geneously poor distribution was compared between patients with single arteries and those with multiple hepatic arteries. The arteries once embolized with coils alone spontaneously recanalized at a significantly higher rate than those with NBCA. A hepatic artery embolization study carried out by Loewe et al.186 using NBCA and ethiodized oil for the treatment of small-bowel neuroendocrine metastases to the liver for the treatment of liver metastases from neuroendocrine small-bowel tumors also concluded that the use of cyanoacrylate as an embolic agent is safe and effective.

The potential of transarterial permanent embolization with the use of a mixture of cyanoa-crylate and lipiodol for treatment of unresectable primary HCC was also assessed by Loewe et al.185 The study included 36 patients with histologically proven HCC who were treated with transarterial embolization of the hepatic arteries. The study indicated that TAE with use of cyanoacrylate and lipiodol for unresectable HCC is a feasible treatment modality. A similar study conducted by Berghammer et al.190 confirmed the safety of the procedure with minimum side effects. Thus, it constitutes a valuable therapeutic option for patients with Okuda stage I and II HCC.

A right gastric artery (RGA) embolization study to prevent acute gastric mucosal lesions caused by an influx of anti-cancer agents into the RGA in patients undergoing repeat HAIC was conducted on 217 patients with malignant hepatic tumors191 using metallic coils and/or a mixture of n-butyl cyanoacrylate (n-BCA). RGA embolization was technically successful in the majority of patients (93%), with the lowest incidence of major complications. The clinical experience of Nadalini et al.192 using isobutyl-2-cyanoacrylate vesical for embolization of the hypogastric arteries in cases of serious hemorrhage of the bladder and prostate is also reported. The effect was immediate results in the majority of cases, a decidedly positive outcome, especially considering the serious conditions of certain neoplastic patients. Isobutyl-2-cyanoacrylate suspension in Lipiodol was also used to treat percutaneous transcatheter embolization of the renal artery in clear cell carcinoma193 in nine patients. In most of the patients, the procedure was found to be palliative, with no complications attributed to the glue or to oil emboli. Preoperative embolization with isobutyl-2-cyanoacrylate by means of an intra-arterial catheter during selective angiography was adopted by Carmignani et al.194 in two cases of carcinoma of the kidney.

Traditional preoperative embolization via a transarterial approach has proved beneficial, but it is often limited by complex vascular anatomy and unfavorable locations.195 Paragangliomas, or glomus tumors, are the neoplasms of the head and neck. They are remarkably vascular, so surgical resection can be complicated by rapid and dramatic blood loss.196 These tumors can develop in the middle ear (glomus tympanicum), the jugular foramen of the skull base (glomus jugulare), or the head and neck area (glomus caroticum, glomus vagale). Surgical removal of these tumors is also often associated with a significant intraoperative bleeding rate because of their vascular nature.197-199 Direct percutaneous injection of n-butyl cyanoacrylate resulted in the effective devasculariza-tion of craniofacial tumors200 and the embolization of oral tumors.201 However, the technique involved additional risks and was not widely adopted. In a study in human patients by Abud et al.,196 the presurgical devascularization was achieved by placing the diagnostic catheter in the common carotid artery to guide the puncture and perform the control angiography during and after the injection of the cyanoacrylate. The percutaneous devascularization of head and neck paragangliomas through the intralesional injection of cyanoacrylate resulted in effective devascularization. It could be a safe and effective technique for managing such clinical lesions.

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