Pharmacokinetics, Safety, and Efficacy of Chemoembolization with Doxorubicin-Loaded Tightly Calibrated Small Microspheres in Patients with Hepatocellular Carcinoma.

PURPOSE: This study examines safety, efficacy, and pharmacokinetics of chemoembolization with loadable microspheres ≤100 µm for hepatocellular carcinoma. MATERIALS AND METHODS: A pilot safety study was performed in 19 patients with size and dose escalation and then 52 patients were enrolled prospectively and randomly assigned to chemoembolization with TANDEM™ loaded with 150 or 100 mg of doxorubicin. RESULTS: The mean diameter of the tumors was 7.28 ± 2.09 cm (range 4-12) and distribution dominant/multiple 51.9/48.1 %. Child A/B distribution was 32/20 (61.5/38.5 %) and etiology HBV/HCV/HBV/HCV-hemochromatosis was 61.6/9.6/9.6/15.4 %. Twenty-five patients were assigned in the low and 27 in the high loading group. There was 1.92 % thirty-day mortality due to lesion rupture. Biliary damage was seen in 3 patients (5.7 %) in the high loading. Mean maximum plasma concentration of doxorubicin C max ± SD was 284.9 ± 276.2 ng/mL for the high and 108.5 ± 77.6 ng/mL for the low loading (p < 0.001). According to m-RECIST overall objective response after two sessions reached 61.22 and 63.82 % at 6 months. Notably, complete target lesion response (CR) after the second session was observed in 28.57 % and maintained in 23.40 % at 6 months. No statistical differences in the local response rates were observed between the two loading groups. Overall survival (OS) at 6 months, 1 , 2, and 3 years was 98.08, 92.3, 88.46, and 82.6 %, respectively. OS and Progression-Free Survival did not demonstrate statistical significance between the two loading groups. CONCLUSION: Initial evidence shows that (a) TANDEM™ achieves high rates of local response and mid-term survival, (b) high loading provides no clinical benefit and is associated with biliary toxicity.

Successful endovascular treatment of transplant intrarenal artery stenosis in renal transplant recipients: Two case reports.

Transplant renal artery stenosis (TRAS) is a relatively rare complication after renal transplantation. The site of the surgical anastomosis is most commonly involved, but sites both proximal and distal to the anastomosis may occur, as well. Angioplasty is the gold standard for the treatment of the stenosis, especially for intrarenal lesions. We report two cases of intrarenal TRAS and successful management with angioplasty without stent placement. Both patients were male, 44 and 55 years old respectively, and they presented with elevated blood pressure or serum creatinine within three months after transplantation. Subsequently, they have undergone angioplasty balloon dilatation with normalization of blood pressure and serum creatinine returning to baseline level. Percutaneous transluminal balloon renal angioplasty is a safe and effective method for the treatment of the intrarenal TRAS.

Chemoembolization of hepatocellular carcinoma with HepaSphere 30-60 µm. Safety and efficacy study.

BACKGROUND: This study examined the safety, pharmacokinetics, and efficacy of transarterial chemoembolization of hepatocellular carcinoma (HCC) using a newly developed size of a superabsorbent polymer drug-eluting embolic material. METHODS: Forty-five patients with documented HCC (Child-Pugh score A/B: 55.5 %/44.5 %) were embolized with HepaSphere microspheres 30-60 µm with escalation of lesion, dose, and frequency of re-embolization. Local response was evaluated with modified response evaluation criteria in solid tumors (mRECIST). Plasma levels of doxorubicin were measured in 24 patients at baseline and at 5, 20, 40, 60, and 120 min, at 6, 24, and 48 h, and at 7 days, respectively, to determine doxorubicin in plasma (Cmax) and area under the curve (AUC). Measurements of three patients who underwent lipiodol-based conventional chemoembolization (c-TACE) were also performed. RESULTS: TACE with HepaSphere was well tolerated with an acceptable safety profile and no 30-day mortality. Response rates were calculated on intention-to-treat basis with complete response (CR) in 17.8 % reaching 22.2 % for the target lesion. Overall partial response (PR) was seen in 51.1 %, stable disease in 20 %, and progressive disease in 11.1 % of patients. Overall objective response (CR + PR), including patients treated at all dosages of doxorubicin, was seen in 68.9 % of cases. After a median follow-up of 15.6 months, 1-year survival is 100 %. Doxorubicin AUC was significantly lower in patients with HepaSphere 30-60 µm (35,195 ± 27,873 ng × min/ml) than in patients with conventional TACE (103,960 ± 16,652 ng × min/ml; p = 0.009). Cmax was also significantly lower with HepaSphere 30-60 µm (83.9 ± 32.1 ng/ml) compared with c-TACE (761.3 ± 58.8 ng/ml; p = 0.002). CONCLUSION: HepaSphere 30-60 µm is an effective drug-eluting embolic material with a favourable pharmacokinetic profile.

Chemoembolization with DC Bead™ for the treatment of hepatocellular carcinoma: an update.

In this review, DC Bead™ for the treatment of hepatocellular carcinoma is discussed. The embolic device and its mechanism of action is described, focusing on the clinical application and the preclinical background. Guidelines for patient selection and management, along with technical considerations for the appropriate use are provided. Clinical details including local response, comparison with conventional chemoembolization and bland embolization, survival and safety issues are also discussed in detail.

Post embolization syndrome in doxorubicin eluting chemoembolization with DC bead.

BACKGROUND/AIMS: The investigation of post embolization syndrome (PES) in patients with hepatocellular carcinoma (HCC) after treatment with doxorubicin loaded DC Bead (DEB-DOX). METHODOLOGY: The study included 237 patients treated with sequential DEB-TACE performed at set time intervals every two months until 3 sessions/6 month f-u. Patients were ECOG 0-1, Child-Stage-A (n=116, 48.9%) and B (n=121, 51%). Embolizations were as selective as possible with DC Bead of 100-300µm in diameter followed by 300-500µm loaded with doxorubicin at 37.5mg/mL of hydrated bead (max:150mg). RESULTS: PES regardless of severity was observed in up to 86.5%. However grade 2 PES ranged between 25% and 42.19% across treatments. Temperatures above 38°C were seen in 22.7% to 38.3% across treatments. No statistically significant increase of PES was seen in beads of 100-300µm in diameter; incidence of fever and pain presented correlation with the extent of embolization (p=0.0001-0.006 across treatments). Baseline tumor diameter was associated with incidence of fever (p=0.0001-0.001). Duration of fever correlated with the extent of embolization (p=0.008). PES was not associated with elevation of liver enzymes and was correlated with degree of necrosis (p<0.001). CONCLUSIONS: PES after DEB-DOX represents tumor response to treatment and does not represent collateral healthy liver damage.

Palliative treatment of rectal carcinoma recurrence using radiofrequency ablation.

PURPOSE: To evaluate the safety and efficacy of CT-guided radiofrequency (RF) ablation for the palliative treatment of recurrent unresectable rectal tumors. MATERIALS AND METHODS: Twenty-seven patients with locally recurrent rectal cancer were treated with computed tomography (CT)-guided RF ablation. Therapy was performed with the patient under conscious sedation with a seven- or a nine-array expandable RF electrode for 8-10 min at 80-110°C and a power of 90-110 W. All patients went home under instructions the next day of the procedure. Brief Pain Inventory score was calculated before and after (1 day, 1 week, 1 month, 3 months, and 6 months) treatment. RESULTS: Complete tumor necrosis rate was 77.8% (21 of a total 27 procedures) despite lesion location. BPI score was dramatically decreased after the procedure. The mean preprocedure BPI score was 6.59, which decreased to 3.15, 1.15, and 0.11 at postprocedure day 1, week 1, and month 1, respectively, after the procedure. This decrease was significant (p < 0.01 for the first day and p < 0.001 for the rest of the follow-up intervals (paired Student t test; n - 1 = 26) for all periods during follow-up. Six patients had partial tumor necrosis, and we were attempted to them with a second procedure. Although the necrosis area showed a radiographic increase, no complete necrosis was achieved (secondary success rate 65.6%). No immediate or delayed complications were observed. CONCLUSION: CT-guided RF ablation is a minimally invasive, safe, and highly effective technique for treatment of malignant rectal recurrence. The method is well tolerated by patients, and pain relief is quickly achieved.

Direct radiofrequency ablation of portal vein tumor thrombus in continuity with hepatocellular carcinoma.

The authors describe the case of a patient with hepatocellular carcinoma and portal vein (PV) tumor thrombus. Radiofrequency (RF) ablation was applied successfully not only to the main tumor but also directly to the invaded PV. On the last imaging follow-up performed at 16 months after RF ablation the PV remained recanalized. Twenty months after the RF ablation, the patient was still alive with good clinical status.

Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study.

Transcatheter arterial chemoembolization (TACE) offers a survival benefit to patients with intermediate hepatocellular carcinoma (HCC). A widely accepted TACE regimen includes administration of doxorubicin-oil emulsion followed by gelatine sponge-conventional TACE. Recently, a drug-eluting bead (DC Bead) has been developed to enhance tumor drug delivery and reduce systemic availability. This randomized trial compares conventional TACE (cTACE) with TACE with DC Bead for the treatment of cirrhotic patients with HCC. Two hundred twelve patients with Child-Pugh A/B cirrhosis and large and/or multinodular, unresectable, N0, M0 HCCs were randomized to receive TACE with DC Bead loaded with doxorubicin or cTACE with doxorubicin. Randomization was stratified according to Child-Pugh status (A/B), performance status (ECOG 0/1), bilobar disease (yes/no), and prior curative treatment (yes/no). The primary endpoint was tumor response (EASL) at 6 months following independent, blinded review of MRI studies. The drug-eluting bead group showed higher rates of complete response, objective response, and disease control compared with the cTACE group (27% vs. 22%, 52% vs. 44%, and 63% vs. 52%, respectively). The hypothesis of superiority was not met (one-sided P = 0.11). However, patients with Child-Pugh B, ECOG 1, bilobar disease, and recurrent disease showed a significant increase in objective response (P = 0.038) compared to cTACE. DC Bead was associated with improved tolerability, with a significant reduction in serious liver toxicity (P < 0.001) and a significantly lower rate of doxorubicin-related side effects (P = 0.0001). TACE with DC Bead and doxorubicin is safe and effective in the treatment of HCC and offers a benefit to patients with more advanced disease.

Image-guided radiofrequency ablation (RFA) of unresectable hepatic tumors using a triple-spiral-shaped electrode needle: initial experience in 34 patients.

We evaluated the safety and efficacy of image-guided radiofrequency ablation (RFA) using a triple-spiral-shaped electrode needle for unresectable primary or metastatic hepatic tumors. Thirty-four patients with 46 index tumors were treated. Ablation zone, morbidity, and complications were assessed. The lesions were completely ablated with an ablative margin of about 1 cm. Five patients (14.7%) with a lesion larger than 4.5 cm had local tumor progression after 1 month and were retreated. Hemothorax, as a major complication, occurred in 1 of 34 patients (3.0%) or 1 of 46 lesions ablated (2.2%). RFA using this new electrode needle can be effective in the treatment of large unresectable hepatic tumors.

A unique case of hepatocellular carcinoma treated with radiofrequency ablation with more than 12 years overall survival: a case report.

The case of a 72-year-old male patient with HCC is presented in whom percutaneous RFA was used as the sole first-line anticancer treatment, since he denied having partial hepatectomy. The patient underwent RFA two more times, at 1.5 years for treating a local tumor progression at the initial ablation site and at 11 years after the first session for treating a new remote intrahepatic recurrence. He revealed a long-term survival of more than 12 years so far and still remains in excellent clinical status.

Image-guided radiofrequency ablation of a pancreatic tumor with a new triple spiral-shaped electrode.

Image-guided, minimally invasive treatment modalities have become an area of considerable interest and research during the last few years for the treatment of primary and secondary liver tumors. We report our experience with an unresectable pancreatic tumor, treated with application of radiofrequency ablation under CT guidance that even though a complication occurred during the procedure, had excellent results on follow-up CT scans.

Radiofrequency ablation of liver metastases from cancer of unknown primary site.

PURPOSE: This retrospective study was performed to review the efficacy of local radiofrequency ablation (RFA) in all the management of liver cancer of unknown primary site (CUP), and to identify possible prognostic features and complications that affect the efficacy of this treatment on survival. MATERIALS AND METHODS: From April 2003 to December 2007, 22 patients (15 men, 7 women) with a total of 36 liver metastasis of CUP and poor response to prior systemic chemotherapy were treated with computed tomography-guided RFA. The median age of patients was 66 years. All patients (22/22) had 1-, 3-, and 6- month follow-up and 8/22 of them had a 12-month followup. RESULTS: The overall median survival of all 22 patients was 10.9 months. Survival was better in patients with lesions 3 cm or smaller. No severe complications, including local seeding, were occured. CONCLUSION: Our study revealed that RFA appears to be an effective, safe and relatively simple alternative procedure for the local ablation of these lesions. These results are more encouraging for lesions 3 cm or smaller, all of which were successfully treated, as proved by the imaging criteria and the statistical analysis. Further prospective trials are needed to determine whether RFA should be proposed for standard protocols.

Percutaneous radiofrequency thermal ablation in the management of lung tumors: presentation of clinical experience on a series of 35 patients.

PURPOSE: To present our results in a series of 35 patients with malignant pulmonary lesions, who underwent radiofrequency thermal ablation (RFA) during a period of 18 months. MATERIALS AND METHODS: In our institution, 55 RFA sessions under computed tomography (CT) guidance were performed on 48 pulmonary malignant lesions (23 inoperable primary and 25 metastatic) in 35 patients. RESULTS: Total necrosis was noted in 19 primary (82.6%) and in 19 metastatic lesions (76%). In four primary (17.4%) and in six metastatic lesions (14%), partial necrosis was achieved, and a second RFA session was performed. The 6-month spiral CT follow-up demonstrated recurrence in seven lesions (14.5%) (four primary and three metastatic), which were treated with an additional RFA session. Two of the patients who underwent the procedure died of disseminated disease after one year, accounting for a 1-year survival rate of 94.2%. Mean survival was 14.48 +/- 3.3 months. CONCLUSION: RFA is an effective method for treating unresectable lung carcinoma and lung metastases.

High-flow renal arteriovenous fistula treated with the Amplatzer vascular plug: implementation of an arterial and venous approach.

We present a 28-year-old man with a large symptomatic arteriovenous fistula (AVF) treated with embolization using the Amplatzer vascular plug (AVP). Although embolization may be considered the first-line therapy in the treatment of AVFs, there is an inherent high risk of migration of the embolic agents into the venous and pulmonary circulations. This case is illustrative of the ease and safety of using this device in high-flow renal AVFs.

Percutaneous radiofrequency ablation of renal cell carcinomas in patients with solitary kidney: 6 years experience.

OBJECTIVE: In this study we attempt to present our clinical experience in RFA under CT-guidance, in patients with renal cell carcinoma in a solitary kidney. MATERIAL AND METHOD: Between October 2000 and June 2005, 18 patients with solitary kidney and renal cell carcinoma underwent percutaneous CT-guided radiofrequency ablation in our institution. Tumors diameter ranged from 1 to 7 cm and there was no evidence of spread beyond the kidney. The RFA-system used was with expandable needle electrode (7 or 9 arrays). Technical success, recurrence and survival rate and complications were accessed. Patients were available for clinical and laboratory evaluation at a mean follow-up time of 31.2 months (range: 12-72 months). RESULTS: In all cases the electrode was successfully placed at the lesion. The 18 tumors were treated with totally 24 RFA sessions. In small (1-3 cm) exophytic tumors technical success was 85.7%. Residual disease was totally seen in 6/18 tumors which required a 2nd RFA session. The recurrence rate was 11.1% but no recurrence was noticed in tumors less than 3 cm in diameter. No major complications were observed. Serum creatinine values were normal in 17/18 patients till the 3rd-month follow-up. Survival ranged from 12 to 72 months. CONCLUSION: RFA is an acceptable alternative for patients with small RCCs in a solitary kidney, which are not ideal candidates for surgical resection as their renal function must be preserved. They have an immediate solution to their clinical problem, under a minimally invasive therapy with no serious complications.

Lower gastrointestinal bleeding treated with transcatheter arterial embolization. Case report and review of the literature.

Acute lower gastrointestinal bleeding, is often a dramatic situation, associated with mortality rate up to 28%. Currently transcatheter alternatives have found their place in the therapeutic spectrum of this situation. An interesting question is when should this procedure be performed and which are the difficulties when performing it. We present the case of a 75-year old woman with acute massive lower gastrointestinal bleeding on the tenth post-operative day of a colic and partial ileal resection. Superselective angiography of the superior mesenteric artery was obtained that disclosed marked contrast extravasation of distal branches of the left colic artery as well as from a small branch feeding the distal enteric anastomoses. Clinical success was achieved after superselective embolization which was accomplished by using polyvinyl alcohol particles. The patient was discharged 5 days later and there were no procedure-related complications during 6-month follow-up period. So, especially in post-operative patients who are considered to be poor candidates for surgical treatment, arterial embolotherapy should be established not only as treatment option, but also as first line therapy for LGI bleeding.

Percutaneous radiofrequency ablation of lung tumors in contact with the aorta: dangerous and difficult but efficient: a report of two cases.

Percutaneous imaging-guided tumor ablation is a widely accepted method for the treatment of primary and secondary lung tumors. Although it is generally feasible and effective for local tumor control, some conditions may affect its feasibility and effectiveness. Herein the authors report their experience with two patients with lung malignancies contiguous to the aorta who were successfully treated with radiofrequency ablation, even though it initially appeared highly risky due to the possible fatal complications.

Overcoming the heat-sink phenomenon: successful radiofrequency thermal ablation of liver tumors in contact with blood vessels.

PURPOSE: To evaluate the efficacy and safety of computed tomography (CT)-guided radiofrequency thermal ablation (RFA) of liver tumors (hepatocellular carcinoma and liver metastases) > 3 mm in diameter that were in contact with blood vessels. MATERIALS AND METHODS: During a 3-year period RFA was performed in 28 patients (age range, 36-83 years; male/female ratio, 17:11) with liver tumors (primary and metastatic) that were in contact with blood vessels > 3 mm in diameter. Tumor diameter ranged from 1.7 to 5.1 cm. To evaluate the immediate response, dual-phase dynamic CT images were obtained after intravenous contrast material administration. Imaging follow-up was at 1, 3, 6, and 12 months post-RFA, and every year thereafter. RESULTS: All of 28 patients were treated with a total of 36 sessions. In 22 (79%) of the patients, complete ablation of the tumor was achieved. The remaining 6 (21%) patients showed irregular peripheral enhancement and underwent a second session. At 1-year follow-up 2 of the tumors showed a recurrent lesion and a new ablation was performed. The local tumor progression rate at 1-year follow-up was 8.7% and disease-free survival was achieved in 82.1% of the patients. Complications occurred in 4 patients (14.3%); 2 patients presented with a small sub-capsular hematoma, and 2 patients had a partial liver infarction. CONCLUSION: RFA is a safe and effective method, even with high-risk tumors adjacent to large blood vessels, which can lead to good results with minimal complications and a low rate of tumor progression.

Endovascular treatment of a ruptured para-anastomotic aneurysm of the abdominal aorta.

We report a case of a ruptured para-anastomotic aortic aneurysm treated with implantation of a bifurcated stent-graft. A 72-year-old patient, who had undergone aortobifemoral bypass for aortoiliac occlusive disease 16 years ago, presented with a ruptured para-anastomotic aortic aneurysm. A bifurcated stent-graft was successfully deployed into the old bifurcated graft. This is the first report of a bifurcated stent-graft being placed through an "end-to-side" anastomosed old aortobifemoral graft. Endovascular treatment of ruptured para-anastomotic aortic aneurysms can be accomplished successfully, avoiding open surgery which is associated with increased mortality and morbidity.