Endovascular brachytherapy of transjugular intrahepatic portosystemic shunt

Cardiovascular Radiation Medicine 2 (2000) 3 ± 6

Endovascular brachytherapy of transjugular intrahepatic portosystemic shunt J. DvorÏaÂka,*, P. HuÊlekb, J. Raupachc, T. VanÏaÂsekb, J. Peteraa, A. Krajinac, J. VanÏaÂseka, Z. Zoula, K. OdraÂzÏkaa, M. LojõÂkc, J. MasÏkovaÂc, V. SÏafkab, P. VodnÏanskyÂd, and J. Fridrichd a

Department of Radiotherapy and Oncology, Charles University Medical School and Teaching Hospital, 50005 Hradec KraÂloveÂ, Czech Republic b 1st Department of Internal Medicine, Charles University Medical School and Teaching Hospital, 50005 Hradec KraÂloveÂ, Czech Republic c Department of Radiology, Charles University Medical School and Teaching Hospital, 50005 Hradec KraÂloveÂ, Czech Republic d Department of Cardiopulmonal and Vascular Diagnostic, Charles University Medical School and Teaching Hospital, 50005 Hradec KraÂloveÂ, Czech Republic Received 25 February 2000; received in revised form 4 April 2000; accepted 10 April 2000

Abstract

Purpose: To evaluate the technical feasibility and efficacy of endovascular brachytherapy with Iridium - 192 in the prevention of restenosis caused by neointimal hyperplasia of transjugular intrahepatic portosystemic shunt (TIPS). Materials and Methods: The endovascular brachytherapy with high dose rate automatic afterloading system was performed in six patients with recurrent of stenosis of TIPS. We used a single dose fraction of 12 Gy delivered at 3 millimeter (mm) from the source axis to the stenotic vessel segment in five patients with spiral Z - stent, and 15 Gy at 5 mm in one patient with Wallstent. Results: Follow - up time ranged from 148 to 639 days. In one patient, restenosis occurred in the treated vessel segment, diagnosed 71 days after endovascular brachytherapy by doppler ultrasound. All other patients were, during the follow - up time, without restenosis in the irradiated vessel segment. Radiation - associated side effects were not observed. Conclusions: Endovascular brachytherapy of TIPS is technically feasible and may be done as a part of the percutaneous revision of the shunt. This pilot study may be the largest experience of treating TIPS restenosis in humans to date. For definitive conclusions, a lot of studies are needed. D 2000 Elsevier Science Inc. All rights reserved.

Keywords:

Vascular restenosis; Intravascular brachytherapy; TIPS; Iridium - 192

1. Introduction In the present paper, we report our experience with endovascular brachytherapy in the prevention of restenosis of transjugular intrahepatic portosystemic shunt (TIPS). TIPS is an effective treatment for symptomatic portal hypertension [3,6]. In 30 ± 70% of patients with TIPS, restenosis occurs in 6 months due to neointimal hyperplasia with an increase of portal hypertension and its consequences [2]. Restenosis is the main limiting factor of long - term efficacy of TIPS procedure. The neointimal hyperplasia narrows the hepatic side of the stented shunt * Corresponding author. Tel.: + 420 - 49 - 583 - 3708; fax: + 420 - 49 551 - 2346.

between the portal and hepatic veins. There have been encouraging reports on the results of endovascular brachytherapy in the treatment of restenosis of coronary [1] and peripheral arteries [7 ±9]. Here, we report the results of endovascular brachytherapy in six patients with recurrent TIPS stenosis.

2. Materials and methods 2.1. Patients Between April 1998 and July 1999, we have performed endovascular brachytherapy in six patients (five men and one woman) with restenosis of TIPS. The

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average age of patients was 39 (22 ± 70) years. The inclusion criteria for endovascular brachytherapy were: restenosis indicated for dilatation of TIPS; advanced liver disease Ð Child B or Child C; and signed informed consent with the treatment. The protocol was approved by local ethical committee. The endovascular brachytherapy was not performed in the case of trombosis of TIPS. For brachytherapy, patients with repeated angioplasty (in five cases) or stent occlusion causing rebleeding (in one case) were selected. There was no differentiation based on the site of restenosis in the indication of brachytherapy. In five patients, restenosis was discovered by doppler ultrasound screening, and in one patient during evaluation for rebleeding. Our routine post - TIPS screening program includes clinical, biochemical and doppler ultrasound evaluation of the patients. The endovascular brachytherapy was applied for the second restenosis after TIPS in two patients, for the third restenosis in three patients and for the fourth restenosis in one patient. The diameters of the original stents were 11 millimeter (mm) in one patient, 11.5 mm in one patient and 12 mm in four patients. The average length of the original stent was 75 mm (60 ± 85 mm). 2.2. Source positioning In all patients, a dilatation of restenosis by TIPS was performed by the standard way at the Department of Radiology. The diameter of the balloon was 12 mm in all patients. The length of the balloon was 60 mm in two patients and 40 mm in four patients. The pressure in the balloon was 15 atm in all cases. The balloon was inflated for a period of 30 s. There was no residual stenosis. The stenosis was measured by angiography. The mean portal vein pressure was 22.2 mm Hg (17 ± 27.5 mm Hg) before dilatation and 16 mm Hg (11 ± 20 mm Hg) after dilatation. The pressure in hepatic vein was 5.8 mm Hg (3.5 ± 8 mm Hg) before dilatation and 8.6 mm Hg (3.5 ± 15 mm Hg) after dilatation. After dilatation of TIPS, the centering catheter sheath was left at the site of restenosis. Then the patient was transported with this sheath to the Department of Radiotherapy and Oncology. Here, with the assistance of interventional radiologist, via this sheath, the 6 - French - diameter catheter with the blind distant end was inserted. Then the calibration catheter was inserted inside the 6- French catheter, and the simulation films were made (Fig. 1). The calibration catheter was withdrawn, the target volume and dose was defined. After irradiation of a single dose of 12 ±15 Gy, the 6 -French catheter and sheath were removed by the interventional radiologist, and the patient was transported to the 1st Department of Internal Medicine for monitoring using the standard way, like after the dilatation of TIPS. After treatment, the irradiated segment of TIPS was examined by doppler ultrasound in all patients. The criterion for the failure of the treatment was if the gradient between portal

Fig. 1. TIPS with the calibration catheter.

vein and right atrium is higher than 12 mm Hg as measured by doppler ultrasound. 2.3. Radiotherapy details The isodose plans were calculated at the planning software Abacus. All patients were irradiated by the source of Iridium - 192 by the high dose rate remote afterloading device Gammamed 12i. The length of irradiated volume was chosen according to the length of the restenosis. The average length of restenosis was 56 mm (30 ±90 mm). The target volume of brachytherapy was the stenotic segment of TIPS as defined by antiography, and safety distance about 10 mm was added to both the proximal and distal margins. The entire length of the restenosis was covered with a homogeneous dose distribution. The dose reference point was selected 3 mm from the source axis in five patients with spiral Z - stent and 5 mm in one patient with Wallstent, and the dose was prescribed at this point. Five patients with spiral Z -stent received a single dose fraction of 12 Gy given at 3 mm from the source axis, and one patient with Wallstent received a single dose fraction of 15 Gy given at 5 mm in the stenotic segment of TIPS. 3. Results The time of hospitalisation after endovascular brachytherapy was not longer than by standard dilatation of TIPS. Follow - up time ranged from 148 to 639 days. In one patient, restenosis occurred in the treated

J. DvorÏaÂk et al. / Cardiovascular Radiation Medicine 2 (2000) 3± 6

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Table 1 Patient number

Date of TIPS

Number of revisions before BRT

Date of revision with BRT

Date of last control

1

30.12.92

2

08.07.98

14.06.99

2 3 4 5

27.05.94 25.05.95 11.04.97 23.10.97

3 1 2 1

02.06.98 04.05.99 06.11.98 21.04.98

24.01.00 30.09.99 25.10.99 24.01.00

6

22.05.98

2

22.07.99

04.01.00

Status functional died 24.09.99 of HCC functional functional functional restenosis 01.07.98 functional

Abbreviations: BRT = brachytherapy; HCC = hepatocellular carcinoma.

vessel segment 71 days after endovascular brachytherapy, discovered by doppler ultrasound. This patient was a 26 - year- old alcoholic who is now without clinical signs of portal hypertension (varices, gastropathy, ascites). There was no need for further radiologic intervention in this patient. One patient was without restenosis at the time of the last control 341 days after endovascular brachytherapy. This patient died of hepatocellular carcinoma (HCC) 427 days after endovascular brachytherapy (BRT). All other patients were, during the follow - up time, without restenosis in the irradiated vessel segment. No radiation - associated side effects were observed (Table 1). 4. Discussion According to our knowledge, there are only two reports in the literature about endovascular brachytherapy of TIPS [5,6]. Our experience shows that endovascular brachytherapy of TIPS is a safe, technically feasible and well tolerated method. In a vessel such as the TIPS shunt with variations in diameter between 8 and 12 mm, there is a potential for great variability in the dose delivered to the walls of the shunt and the surrounding structures. The risk of this variability in the dose is potential lower treatment dose to the stenotic segment of the wall of TIPS and, on the other hand, potential risk of radiation damage of surrounding liver tissue. In the present cohort of patients, we used endovascular brachytherapy as ``rescue procedure'' in patients requiring multiple dilatations of restenosis in short intervals. The main technical problem is the centering of the catheter in TIPS (Fig. 1). The centering is less problematic in the case of gamma radiation compared to beta radiation because of longer radius of gamma radiation than beta radiation. TIPS stenosis may be an ideal lesion for treatment by endovascular brachytherapy when the problem of centering in a large vessel is solved [6]. Our effort now is to look for the optimal centering of the source of irradiation, e.g. to use the balloon or the basket. There could be alternative methods of radiation treatment of TIPS such as with radioactive stents, a beta source within a

balloon or on a wire or external beam radiation. Radioactive stents were successfully used in the prevention of coronary artery restenosis [4]. Radioactive stents for TIPS would have larger dimensions than intracoronary stents. These larger dimensions of radioactive stents for TIPS would be probably connected with technical problems. Beta source 32phosphorus - filled balloon angioplasty catheter was used in porcine model to reduce pseudointimal hyperplasia in TIPS [5] In this study, intraluminal irradiation was used after initial TIPS placement. That is a different situation than the one in our study, where endovascular brachytherapy was not used after initial TIPS placement, but in repeated restenosis [5]. In contrast to human study, the experiments [5] were performed in normal animals with no portal hypertension and normal coagulation, which may explain the different effect on TIPS patency. External beam radiation is successfully used in arteriovenous fistulas because of their unique anatomic advantage in their very superficial location [7]. In the case of TIPS, the integral dose to the liver tissue from the external beam radiation would be probably unacceptable. The endovascular brachytherapy of TIPS enlarges the indications of brachytherapy. This study may be the largest experience of treating TIPS restenosis in humans to date. This is a pilot study for the evaluation of technical feasibility, and for definitive conclusions, a lot of studies are needed.

References [1] Condado JA, Curdiel O, Espinosa R, et al. Percutaneous transluminal coronary angioplasty (PTCA) and intracoronary radiation therapy (ICRT): a possible new modality for the treatment of coronary restenosis: a preliminary report of the first 10 patients treated with intracoronary radiation therapy [abstract]. J Am Coll Cardiol 1995;228A. [2] Freedman AM, Sanayl AJ. Complications of transjugular intrahepatic portosystemic shunts. Sem Intervent Radiol 1994;11:161 ± 77. [3] Hausegger KA, Sternthal HM, Klein GE, et al. Transjugular intrahepatic portosystemic shunt: angiographic follow - up and secondary interventions. Radiology 1994;191:177 ± 81. [4] Herhlein C, Zimmermann M, Metz J, et al. Radioactive stent implantation inhibits neointimal proliferation in non - atherosclerotic rabbits. Circulation (abstr.) 1993;88:I ± 65.

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[5] Lessie T, Yoon HC, Nelson HA, et al. Intraluminal irradiation for TIPS stenosis: preliminary results in a swine model. JVIR 1999; 10(7):899 ± 906. [6] Martin LG. Radiation for peripherals application: technical aspects. In: Waksman R, King SB, Crocker IR, et al., editors. Vascular brachytherapy. Veenendaal: Nucletron, 1996. pp. 249 ± 57. [7] Nori D, Parikh S, Moni J, et al. Management of peripheral vascular disease: innovative approaches using radiation therapy. Int J Radiat Oncol Biol Phys 1996;36(4):847 ± 56.

[8] Rubin P, Waksman R. Editor's note. Int J Radiat Oncol Biol Phys 1996;36(4):763 ± 6. [9] Schopohl B, Liermann D, Pohlit LJ, et al. 192Ir endovascular brachytherapy for avoidance of intimal hyperplasia after percutaneous transluminal angioplasty and stent implantation in peripheral vessels: 6 years of experiences. Int J Radiat Oncol Biol Phys 1996;36(4): 835 ± 40.