- Email: [email protected]
Selective internal radiation therapy of hepatic tumours: Is coiling of the gastroduodenal artery always beneficial?
Clinical Radiology 69 (2014) e216ee222
Contents lists available at ScienceDirect
Clinical Radiology journal homepage: www.clinicalradiologyonline.net
Selective internal radiation therapy of hepatic tumours: Is coiling of the gastroduodenal artery always beneficial? J. Schelhorn a, *, J. Theysohn a, J. Ertle b, J.F. Schlaak b, S. Mueller c, A. Bockisch c, T. Lauenstein a a
Department of Diagnostic and Interventional Radiology, University Hospital Essen, Germany Department of Gastroenterology und Hepatology, University Hospital Essen, Germany c Clinic of Nuclear Medicine, University Hospital Essen, Germany b
article in formation Article history: Received 26 September 2013 Received in revised form 23 December 2013 Accepted 24 December 2013
AIM: To assess the effect of gastroduodenal artery (GDA) occlusion prior to selective internal radiation therapy (SIRT) with regards to arterial hepato-intestinal collateralization (HIC). MATERIALS AND METHODS: Six hundred and six patients were scheduled for SIRT between 2006 and 2012 at University Hospital Essen, Germany. Digital subtraction angiography (DSA) followed by administration of 99m-technetium labelled human serum albumin microspheres (99mTc-HSAM) and single-photon emission computed tomography combined with computed tomography (SPECT/CT) was initially performed. Depending on vascular anatomy and hepatic tumour load, GDA coil embolization was considered. In subsequent 99mTc-HSAM rescans or therapeutic DSA, HIC and its consequences for SIRT were analysed. RESULTS: The GDA was occluded in 86 of 606 patients (14%). Twenty-two of these 86 patients did not undergo SIRT due to the patients’ clinical status or SIRT contraindications. In 28 of the remaining 64 patients, newly apparent or reopened HIC were seen either at the site of the proximal GDA (n ¼ 21) or in the periphery of the hepatic arteries (n ¼ 7). In 25 of these 28 patients, the HIC could be occluded or the catheter position could be changed achieving a safe 90Y application. However, due to the newly visible HIC in three of 28 patients, SIRT was regarded as unsafe and was abandoned. CONCLUSION: Coil embolization of the GDA may induce arterial hepato-intestinal collaterals. Although most of these collaterals do not impede 90Y administration, SIRT may become unfeasible in specific occasions. Hence, segmental or lobar SIRT instead of a whole-liver approach with coiling of the GDA is recommended. Ó 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Introduction Selective internal radiation therapy (SIRT) is based on the intra-arterial administration of microspheres with the beta * Guarantor and correspondent: J. Schelhorn, Department of Diagnostic and Interventional Radiology, University Hospital Essen, Hufelandstrasse 55, 45147 Essen, Germany. Tel.: þ4920172384515. E-mail address: [email protected] (J. Schelhorn).
emitter 90-yttrium (90Y). It is increasingly used as a treatment for unresectable liver tumours.1e13 Due to the almost exclusive arterial blood supply of the tumours but the dual (portal venous > arterial) blood supply of normal liver tissue, the intra-arterial administration of 90Y allows local tumour therapy with partial sparing of healthy liver tissue. Owing to the high administered radioactivity of approximately 1e3 GBq,3,8,14 even a small amount of non-targeted diversion of 90Y to other organs may lead to therapy-
0009-9260/$ e see front matter Ó 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.crad.2013.12.015
J. Schelhorn et al. / Clinical Radiology 69 (2014) e216ee222
resistant radiation gastritis, gastrointestinal ulcers causing perforation, and pancreatitis.1,15e18 In order to prevent any non-target radiation of adjacent organs coil embolization of extrahepatic vessels, including the gastroduodenal artery (GDA), can be performed.1,15,19 However, due to haemodynamic changes, coil embolization may result in recruitment of pre-existing but formerly not relevantly perfused hepatointestinal collaterals (HICs), reopening of coiled vessels or side branches, or even the development of new HICs, which may increase the risk of gastrointestinal complications during subsequent SIRT.20 The aim of the present study was to assess the rate and localization of reopened or newly apparent HICs after GDA occlusion and their impact on SIRT in patients treated at University Hospital Essen, Germany.
Material and methods Patients Six hundred and six patients (464 male, 142 female, mean age 64.5 years) were scheduled for SIRT between October 2006 and December 2012 at University Hospital Essen. Selection criteria for standard SIRT were based on contraindications for transarterial chemoembolization (TACE), including portal vein thrombosis or a hepatic tumour burden that was too large to be treated using TACE. Hepatic tumours included hepatocellular carcinoma (n ¼ 476), cholangiocarcinoma (n ¼ 14), or hepatic metastases (n ¼ 116). Informed consent for angiography and SIRT was obtained, and retrospective analysis and use of data were approved by the local ethic committee.
Pretreatment digital subtraction angiography (DSA) DSA was performed using a biplanar DSA system (Philips Allura, Philips Healthcare, Best, The Netherlands; or Toshiba Infinix DP-i, Toshiba Medical Systems, Tokyo, Japan). Using the Seldinger technique, a 5 F guiding catheter (Sidewinder1, Sindwinder-2 or Cobra-2; Terumo Europe, Leuven, Belgium) was inserted via transfemoral access. Selective DSA of the coeliac trunk and the superior mesenteric artery was performed administering 15 ml of contrast agent (iobitridol; Xenetix, Guerbet, Roissy, France) at a rate of 5 ml/s by an automatic injector (Tyco Healthcare, Mansfield, MA, USA). Selective DSA was acquired at 80 kV, 70 mAs, and a rate of two images per second. The GDA was occluded in two settings: (a) in patients with whole-liver treatment or (b) in patients with lobar treatment when the injection side/catheter position was close to the origin of the GDA. Occlusion was achieved by permanent coil embolization using interlocking detachable or pushable coils (Boston Scientific, Natick, MA, USA or Cook Medical, Bloomington, IN, USA) and a microcatheter (Rebar 0.27 inch, ev3 Europe SAS, Paris, France). In a next step, the position for administration of the 99mtechnetium-labelled human serum albumin microspheres (99mTc-HSAM) was defined for the right, left, or both hepatic lobes and a total of 150 MBq 99mTc-HSAM (B20, ROTOP Pharmaka AG, Dresden, Germany) was injected from the
e217
defined microcatheter positions. Subsequent anterioreposterior planar gamma camera images of the trunk were recorded and after defining regions of interest for the lungs and the liver, the hepatopulmonary lung shunt fraction was calculated dividing the total lung count by the sum of the lung and liver count.21 Furthermore, combined single-photon emission computed tomography/computed tomography (SPECT/CT) analysis was performed to exclude any extrahepatic tracer accumulation.19,22,23
SIRT with 90-yttrium Therapeutic DSA for 90Y administration (TheraSphereÔ, BTG, Hertfordshire, United Kingdom) was performed in the same way as the pretreatment DSA. Initially, diagnostic DSA was carried out to check for impermeability of the previously coil embolized GDA and for potential newly apparent or reopened HIC. If HIC were detected, a reattempt to occlude the HICs using permanent coiling was undertaken followed by repeat 99mTc-HSAM. If this was not feasible, the microcatheter position was changed for 90Y administration in order to allow for a safe distance between the injection site and the HIC, for the most part followed by repeat 99mTcHSAM. However, the catheter tip was never positioned more proximally than the position that had been demonstrated to be safe by the 99mTc-HSAM SPECT/CT. If microcatheter repositioning was not feasible due to the peripheral localization of HIC, SIRT was considered as unsafe and was cancelled.
Follow-up Clinical symptoms such as dyspepsia, acid regurgitation, or abdominal pain were assessed directly after DSA and in clinical follow-up visits. Patients were discharged 48 h after 90 Y administration and had been strictly instructed to contact the hospital in case of any adverse event.
Results In 86 of 606 patients (14%, 95% CI: 12e17%), the GDA was initially occluded. Twenty-two of these 86 patients did neither undergo SIRT nor further SIRT evaluation due to clinical deterioration (n ¼ 9), interim liver transplantation (n ¼ 1), insufficient tumoural 99mTc-HSAM accumulation (n ¼ 4), a predicted lung dose exceeding 30 Gy (n ¼ 4), preference for other therapeutic options such as edotreotide treatment in hepatic metastasis of neuroendocrine tumours (n ¼ 3), or final refusal of SIRT by the patient (n ¼ 1). Hence, 64 patients were further scheduled for SIRT (n ¼ 2) or received SIRT (n ¼ 62). The median time interval between initial DSA, including GDA coiling, and subsequent DSA with SIRT and Re-HSA scan was 35 days (range 2e76 days). The median time interval between initial DSA and SIRT was 36 days (range 15e115 days). These long time intervals were caused by several repeated 99mTc-HSAM SPECT/CT examinations due to gastrointestinal 99mTc-HSAM accumulation (n ¼ 11), administration of sorafenib
e218
J. Schelhorn et al. / Clinical Radiology 69 (2014) e216ee222
Figure 1 Flowchart: SIRT evaluation of all 606 patients.
(Nexavar, Bayer AG, Leverkusen, Germany) for lung shunt reduction (n ¼ 1), one failed SIRT due to microcatheter occlusion during 90Y administration (n ¼ 1), and interim surgical resection of the HIC (n ¼ 1). Of the 62 patients who finally received SIRT, 50 had a lobar approach with 90Y administration into the right, left, or both hepatic arteries and only 12 a whole-liver approach with 90Y administration into the main hepatic artery. In 36 of 64 patients (56%), the therapeutic DSA did not reveal any newly apparent or reopened HICs, resulting in a straightforward SIRT. All 36 patients tolerated SIRT well. In 28 of 64 patients (44%, 95% CI: 32e56%), new or reopened HICs were detected based on DSA (Fig 1). In 21 of 28 patients (75%), these HICs were located at the proximal stump of the occluded GDA or at the proximal common hepatic artery (Fig 2). In 15 of these 21 patients, the HIC did not interfere
with microcatheter positioning for 90Y administration due to a sufficiently safe distance between the HIC and the 90Y injection site. However, in six of 21 patients a more distal microcatheter position had to be chosen to avoid nontargeted microsphere diversion during SIRT. In all 21 patients, SIRT was performed without any complications. In seven of the 28 patients with HICs (25%), the HICs were detected in the periphery of the hepatic arterial bed. In these patients, HICs arose from branches of the right (n ¼ 4), the left (n ¼ 2), or both hepatic arteries (n ¼ 1). In all seven patients, the newly apparent HICs were too small for probing and coil embolization. In four of the seven patients, a more distal microcatheter positioning was achievable; hence, SIRT could be safely performed (Fig 3). In three out of these seven patients, neither coil embolization nor a more distal microcatheter positioning was feasible. One of these patients was excluded from SIRT without any repeat 99mTc-HSAM administration due to HICs (Fig 4). In two other patients, the repeated 99mTc-HSAM administration confirmed relevant hepato-intestinal shunting, and therefore, SIRT was considered unsafe and was primarily abandoned. Extraordinarily, in one of these three patients, the interdisciplinary tumour team opted for surgical removal of the HIC. After this invasive surgical SIRT preparation, a repeated pretreatment DSA showed no remaining HIC or gastrointestinal 99mTc-HSAM accumulation (Fig 5). Thus, SIRT could be performed and was tolerated well in this patient. SIRT could not be performed in the remaining two patients.
Discussion GDA coil embolization prior to SIRT is commonly performed in many centres. However, in the present study, recruitment of preformed HICs that were not relevantly
Figure 2 Initial hepaticography visualising a patent GDA (a). After GDA coil embolization a reopened side branch on the GDA stump (considered as a proximal HIC) was detected during DSA (b). In cases like these, SIRT can be safely performed with a more distal microcatheter position.
J. Schelhorn et al. / Clinical Radiology 69 (2014) e216ee222
e219
Figure 3 In the initial celiacography (a) and hepaticography (b) a patent GDA is visible without any other detectable HICs. After GDA occlusion peripheral HICs arising from the right hepatic artery were detected (c). SIRT was still possible because a more distal microcatheter position was achievable (d).
perfused previously and reopening of coiled or even newly developed HICs were found in 44% of patients after GDA occlusion. In the majority of cases, SIRT was still feasible after recoiling or modification of the microcatheter position. However, in 5% of patients, this was not possible and SIRT had to be abandoned. Hence, coil embolization of the GDA with consecutively developed or newly perfused HICs can permanently exclude patients from SIRT. Therefore, a primary lobar or segmental SIRT approach is preferred and GDA coiling avoided to eliminate the risk of the rare development of peripheral HICs. Furthermore, as a future perspective, with currently developed anti-reflux devices, one may even choose a whole-liver SIRT approach with a relatively proximal microcatheter position without the need for GDA coiling to avoid any risk of reopening or recruitment of HICs (Fischman A, Arepally A, Sze D et al. Radioembolisation without prophylactic coil embolization
of patent proximal extrahepatic vasculature: use of an antireflux infusion system. In: Cirse 2013. Cardiovasc Intervent Radiol. 2013 Sep;36(3) Supplement: S221.) It is crucial to prevent 90Y distribution into small gastrointestinal vessels as this may lead to non-healing gastrointestinal ulcers.1 Currently, rates of radiationinduced gastritis and gastrointestinal ulcerations of 0.7e4.8% in SIRT have been reported.18,24,25 These ulcerations are predominantly located in the stomach and duodenum on the serosal surface and can be refractory to medical therapy. They may lead to gastrointestinal bleeding, bowel obstruction, or even perforation, and in severe cases surgical therapy is required.26 To overcome this problem, different strategies exist. Either the critical vessels can be occluded or a more peripheral microcatheter position for 90Y administration can be chosen. However, the latter strategy may result in the need of numerous 90Y
e220
J. Schelhorn et al. / Clinical Radiology 69 (2014) e216ee222
Figure 4 After GDA coil embolization newly apparent peripheral HICs were detected in DSA resulting in the impracticality of SIRT: primary coeliacography with patent GDA (a), in the repeated DSA multiple newly visible HIC were seen in the hepaticography (b) and after separate probing of common (c), right (d) and left hepatic artery (e).
injections, which can be time-consuming, technically challenging, and cumbersome. Therefore, some authors propagate the occlusion of most gastrointestinal shunt vessels prior to SIRT.1,15,19,27 This approach was chosen by Abdelmaksoud et al.20 who investigated 122 patients undergoing whole-liver SIRT after endovascular skeletonization of the hepatic artery. Embolization of all hepatico-enteric vessels was performed in the pretreatment DSA by this group. Vessel occlusion was verified by C-arm computed tomography (CACT) and 99mtechnetium macro-aggregated albumin (99mTc-MAA) scintigraphy. During the following treatment session, DSA and CACT were repeated to investigate for new or reopened HICs. In 42 patients (34%), Abdelmaksoud et al. found HICs requiring recoiling. Despite re-embolization, three patients developed gastric or duodenal ulcerations. The rate of newly apparent or reopened HICs reported by this group is comparable to the number of HIC in the present cohort. However, in the present study different clinical consequences were drawn from these findings. Owing to safety reasons, three patients with peripheral HICs were excluded from SIRT. However, the majority of the present patients received SIRT and none developed any gastrointestinal adverse events, which is very important in the palliative setting of SIRT. The above-described facts underline the complex situation that can be found after coiling of hepato-intestinal shunt vessels. Although the majority of patients do not face any problems after GDA occlusion, patients with new or reopened HICs should be triaged into groups of (a) re-embolization, (b) change of microcatheter position, and (c) exclusion from SIRT. Clearly, there are no strict guidelines for this triage and patients with HICs should be discussed individually.
Petroziello et al.28 described that after pretreatment side-branch embolization, eight of their 56 patients (14%) presented with recanalized or newly developed HICs and that seven out of the 110 primarily coiled vessels (6%) had newly developed collaterals.28 Patients with reopened or new HIC were treated, where possible, by re-embolization or a more distal microcatheter position. In one patient, SIRT was not performed for safety reasons. Compared with the present results and the findings of Abdelmaksoud et al., the number of newly apparent or reopened collaterals described by Petroziello et al. is much lower. One explanation could be that in the present study only coil embolization of the GDA was analysed. It is conceivable that after occlusion of a large vessel, the haemodynamic changes are more prone to lead to new or reopened HICs than after occlusion of smaller vessels such as the right gastric artery or even smaller accessory arteries as described by Petroziello et al. Most recently, Enriquez et al.29 investigated predisposing technical factors for GDA recanalization after coil embolization. One hundred and forty-two patients scheduled for either radioembolization or hepatic arterial chemotherapy were enrolled. In all subjects, the GDA was occluded using fibred coils. Different factors, including length of the coil pack, distance between GDA origin and coils, and platelet count, were analysed regarding the impact on GDA recanalization. Recanalization was undertaken in 20% of the patients. The only predisposing factor for recanalization was the distance between the GDA origin and the coil: the further the coil was from the origin, the more likely the GDA was recanalized. The other factors analysed did not have any impact on the recanalization rate. Again, the number of
J. Schelhorn et al. / Clinical Radiology 69 (2014) e216ee222
e221
Figure 5 The patent GDA (a) was initially embolized using coils (b). Afterwards, newly visible peripheral HICs were detected (c, d) and it was only after surgical removal of these HICs (e, f) that no more gastrointestinal 99mTc-HSAM accumulation was detected, and SIRT could finally be performed.
patients (approximately 20%) with recanalization is not high, but these patients require recoiling or a more distal microcatheter position, often resulting in a segmental approach. However, Enriquez did not focus on the location of the HICs and did not distinguish between proximal and peripheral HICs, which the present authors consider more critical because they may render even lobar or segmental SIRT impossible. These peripheral HIC were found in 11% of the present patients after GDA occlusion.
The present study is not without limitations. First, the diagnostic DSA was performed by different interventional radiologists. However, the procedure for SIRT preparation is standardized and all images were re-analysed for this study. As a further limitation, only coils were used for GDA occlusion. Other techniques, including the combination of coils and gelfoam or Amplatzer plugs, may result in a different incidence of HICs. Furthermore, this was a retrospective study. Of course, it would be favourable to perform
e222
J. Schelhorn et al. / Clinical Radiology 69 (2014) e216ee222
a prospective trial comparing the outcome of two patient groups with and without protective embolization of the GDA prior to SIRT. In summary, a lobar or segmental SIRT instead of a whole-liver approach and avoidance of GDA coiling are recommended to reduce the risk of peripheral HIC development.
References 1. Salem R, Thurston KG. Radioembolization with 90-yttrium microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies. Part 2: special topics. J Vasc Interv Radiol 2006;17:1425e39. 2. Salem R, Thurston KG. Radioembolization with yttrium-90 microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies. Part 3: comprehensive literature review and future direction. J Vasc Interv Radiol 2006;17:1571e93. 3. Salem R, Thurston KG. Radioembolization with 90-yttrium microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies. Part 1: technical and methodologic considerations. J Vasc Interv Radiol 2006;17:1251e78. 4. Salem R, Lewandowski RJ, Atassi B, et al. Treatment of unresectable hepatocellular carcinoma with use of 90Y microspheres (TheraSphere): safety, tumor response, and survival. J Vasc Interv Radiol 2005; 16:1627e39. 5. Salem R, Lewandowski RJ, Sato KT, et al. Technical aspects of radioembolization with 90Y microspheres. Tech Vasc Interv Radiol 2007;10:12e29. 6. Lewandowski RJ, Sato KT, Atassi B, et al. Radioembolization with 90Y microspheres: angiographic and technical considerations. Cardiovasc Intervent Radiol 2007;30:571e92. 7. Powerski MJ, Scheurig-Munkler C, Banzer J, et al. Clinical practice in radioembolization of hepatic malignancies: a survey among interventional centers in Europe. Eur J Radiol 2012;81:e804e11. 8. Wybranski C, Mohnike K, Ricke J. Minimally invasive tumor ablation in the liver. Anasthesiol Intensivmed Notfallmed Schmerzther 2009; 44(670):7. quiz 679. 9. Dudeck O, Zeile M, Wybranski C, et al. Early prediction of anticancer effects with diffusion-weighted MR imaging in patients with colorectal liver metastases following selective internal radiotherapy. Eur Radiol 2010;20:2699e706. 10. Mazzaferro V, Sposito C, Bhoori S, et al. Yttrium-90 radioembolization for intermediate-advanced hepatocellular carcinoma: a phase 2 study. Hepatology 2013;57:1826e37. 11. Sangro B, Carpanese L, Cianni R, et al. Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation. Hepatology 2011;54:868e78. 12. Salem R, Lewandowski RJ, Mulcahy MF, et al. Radioembolization for hepatocellular carcinoma using yttrium-90 microspheres: a comprehensive report of long-term outcomes. Gastroenterology 2010;138:52e64. 13. Hilgard P, Hamami M, Fouly AE, et al. Radioembolization with yttrium90 glass microspheres in hepatocellular carcinoma: European experience on safety and long-term survival. Hepatology 2010;52:1741e9.
14. Grober OS, Nultsch M, Laatz K, et al. Radioembolization with Y-labeled microspheres: post-therapeutic therapy validation with Bremsstrahlung-SPECT. Z Med Phys 2011;21:274e80. 15. Paprottka PM, Jakobs TF, Reiser MF, et al. Practical vascular anatomy in the preparation of radioembolization. Cardiovasc Intervent Radiol 2012;35:454e62. 16. Pech M, Kraetsch A, Wieners G, et al. Embolization of the gastroduodenal artery before selective internal radiotherapy: a prospectively randomized trial comparing platinum-fibered microcoils with the Amplatzer Vascular Plug II. Cardiovasc Intervent Radiol 2009;32: 455e61. 17. Dudeck O, Bulla K, Wieners G, et al. Embolization of the gastroduodenal artery before selective internal radiotherapy: a prospectively randomized trial comparing standard pushable coils with fibered interlock detachable coils. Cardiovasc Intervent Radiol 2011;34:74e80. 18. Naymagon S, Warner RR, Patel K, et al. Gastroduodenal ulceration associated with radioembolization for the treatment of hepatic tumors: an institutional experience and review of the literature. Dig Dis Sci 2010;55:2450e8. 19. Kennedy A, Nag S, Salem R, et al. Recommendations for radioembolization of hepatic malignancies using yttrium-90 microsphere brachytherapy: a consensus panel report from the radioembolization brachytherapy oncology consortium. Int J Radiat Oncol Biol Phys 2007;68:13e23. 20. Abdelmaksoud MH, Hwang GL, Louie JD, et al. Development of new hepaticoenteric collateral pathways after hepatic arterial skeletonization in preparation for yttrium-90 radioembolization. J Vasc Interv Radiol 2010;21:1385e95. 21. Dezarn WA, Cessna JT, DeWerd LA, et al. Recommendations of the American Association of Physicists in Medicine on dosimetry, imaging, and quality assurance procedures for 90Y microsphere brachytherapy in the treatment of hepatic malignancies. Med Phys 2011;38:4824e45. 22. Hamami ME, Poeppel TD, Muller S, et al. SPECT/CT with 99mTc-MAA in radioembolization with 90Y microspheres in patients with hepatocellular cancer. J Nucl Med 2009;50:688e92. 23. Ahmadzadehfar H, Sabet A, Muckle M, et al. 99mTc-MAA/90Y-Bremsstrahlung SPECT/CT after simultaneous Tc-MAA/90Y-microsphere injection for immediate treatment monitoring and further therapy planning for radioembolization. Eur J Nucl Med Mol Imaging 2011;38:1281e8. 24. Kennedy AS, McNeillie P, Dezarn WA, et al. Treatment parameters and outcome in 680 treatments of internal radiation with resin 90Y-microspheres for unresectable hepatic tumors. Int J Radiat Oncol Biol Phys 2009;74:1494e500. 25. Sato KT, Lewandowski RJ, Mulcahy MF, et al. Unresectable chemorefractory liver metastases: radioembolization with 90Y microspheresdsafety, efficacy, and survival. Radiology 2008;247:507e15. 26. Collins J, Salem R. Hepatic radioembolization complicated by gastrointestinal ulceration. Semin Intervent Radiol 2011;28:240e5. 27. Liu DM, Salem R, Bui JT, et al. Angiographic considerations in patients undergoing liver-directed therapy. J Vasc Interv Radiol 2005;16:911e35. 28. Petroziello MF, McCann JW, Gonsalves CF, et al. Side-branch embolization before 90Y radioembolization: rate of recanalization and new collateral development. AJR Am J Roentgenol 2011;197:W169e74. 29. Enriquez J, Javadi S, Murthy R, et al. Gastroduodenal artery recanalization after transcatheter fibered coil embolization for prevention of hepaticoenteric flow: incidence and predisposing technical factors in 142 patients. Acta Radiol 2013;54:790e4.
Contents lists available at ScienceDirect
Clinical Radiology journal homepage: www.clinicalradiologyonline.net
Selective internal radiation therapy of hepatic tumours: Is coiling of the gastroduodenal artery always beneficial? J. Schelhorn a, *, J. Theysohn a, J. Ertle b, J.F. Schlaak b, S. Mueller c, A. Bockisch c, T. Lauenstein a a
Department of Diagnostic and Interventional Radiology, University Hospital Essen, Germany Department of Gastroenterology und Hepatology, University Hospital Essen, Germany c Clinic of Nuclear Medicine, University Hospital Essen, Germany b
article in formation Article history: Received 26 September 2013 Received in revised form 23 December 2013 Accepted 24 December 2013
AIM: To assess the effect of gastroduodenal artery (GDA) occlusion prior to selective internal radiation therapy (SIRT) with regards to arterial hepato-intestinal collateralization (HIC). MATERIALS AND METHODS: Six hundred and six patients were scheduled for SIRT between 2006 and 2012 at University Hospital Essen, Germany. Digital subtraction angiography (DSA) followed by administration of 99m-technetium labelled human serum albumin microspheres (99mTc-HSAM) and single-photon emission computed tomography combined with computed tomography (SPECT/CT) was initially performed. Depending on vascular anatomy and hepatic tumour load, GDA coil embolization was considered. In subsequent 99mTc-HSAM rescans or therapeutic DSA, HIC and its consequences for SIRT were analysed. RESULTS: The GDA was occluded in 86 of 606 patients (14%). Twenty-two of these 86 patients did not undergo SIRT due to the patients’ clinical status or SIRT contraindications. In 28 of the remaining 64 patients, newly apparent or reopened HIC were seen either at the site of the proximal GDA (n ¼ 21) or in the periphery of the hepatic arteries (n ¼ 7). In 25 of these 28 patients, the HIC could be occluded or the catheter position could be changed achieving a safe 90Y application. However, due to the newly visible HIC in three of 28 patients, SIRT was regarded as unsafe and was abandoned. CONCLUSION: Coil embolization of the GDA may induce arterial hepato-intestinal collaterals. Although most of these collaterals do not impede 90Y administration, SIRT may become unfeasible in specific occasions. Hence, segmental or lobar SIRT instead of a whole-liver approach with coiling of the GDA is recommended. Ó 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Introduction Selective internal radiation therapy (SIRT) is based on the intra-arterial administration of microspheres with the beta * Guarantor and correspondent: J. Schelhorn, Department of Diagnostic and Interventional Radiology, University Hospital Essen, Hufelandstrasse 55, 45147 Essen, Germany. Tel.: þ4920172384515. E-mail address: [email protected] (J. Schelhorn).
emitter 90-yttrium (90Y). It is increasingly used as a treatment for unresectable liver tumours.1e13 Due to the almost exclusive arterial blood supply of the tumours but the dual (portal venous > arterial) blood supply of normal liver tissue, the intra-arterial administration of 90Y allows local tumour therapy with partial sparing of healthy liver tissue. Owing to the high administered radioactivity of approximately 1e3 GBq,3,8,14 even a small amount of non-targeted diversion of 90Y to other organs may lead to therapy-
0009-9260/$ e see front matter Ó 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.crad.2013.12.015
J. Schelhorn et al. / Clinical Radiology 69 (2014) e216ee222
resistant radiation gastritis, gastrointestinal ulcers causing perforation, and pancreatitis.1,15e18 In order to prevent any non-target radiation of adjacent organs coil embolization of extrahepatic vessels, including the gastroduodenal artery (GDA), can be performed.1,15,19 However, due to haemodynamic changes, coil embolization may result in recruitment of pre-existing but formerly not relevantly perfused hepatointestinal collaterals (HICs), reopening of coiled vessels or side branches, or even the development of new HICs, which may increase the risk of gastrointestinal complications during subsequent SIRT.20 The aim of the present study was to assess the rate and localization of reopened or newly apparent HICs after GDA occlusion and their impact on SIRT in patients treated at University Hospital Essen, Germany.
Material and methods Patients Six hundred and six patients (464 male, 142 female, mean age 64.5 years) were scheduled for SIRT between October 2006 and December 2012 at University Hospital Essen. Selection criteria for standard SIRT were based on contraindications for transarterial chemoembolization (TACE), including portal vein thrombosis or a hepatic tumour burden that was too large to be treated using TACE. Hepatic tumours included hepatocellular carcinoma (n ¼ 476), cholangiocarcinoma (n ¼ 14), or hepatic metastases (n ¼ 116). Informed consent for angiography and SIRT was obtained, and retrospective analysis and use of data were approved by the local ethic committee.
Pretreatment digital subtraction angiography (DSA) DSA was performed using a biplanar DSA system (Philips Allura, Philips Healthcare, Best, The Netherlands; or Toshiba Infinix DP-i, Toshiba Medical Systems, Tokyo, Japan). Using the Seldinger technique, a 5 F guiding catheter (Sidewinder1, Sindwinder-2 or Cobra-2; Terumo Europe, Leuven, Belgium) was inserted via transfemoral access. Selective DSA of the coeliac trunk and the superior mesenteric artery was performed administering 15 ml of contrast agent (iobitridol; Xenetix, Guerbet, Roissy, France) at a rate of 5 ml/s by an automatic injector (Tyco Healthcare, Mansfield, MA, USA). Selective DSA was acquired at 80 kV, 70 mAs, and a rate of two images per second. The GDA was occluded in two settings: (a) in patients with whole-liver treatment or (b) in patients with lobar treatment when the injection side/catheter position was close to the origin of the GDA. Occlusion was achieved by permanent coil embolization using interlocking detachable or pushable coils (Boston Scientific, Natick, MA, USA or Cook Medical, Bloomington, IN, USA) and a microcatheter (Rebar 0.27 inch, ev3 Europe SAS, Paris, France). In a next step, the position for administration of the 99mtechnetium-labelled human serum albumin microspheres (99mTc-HSAM) was defined for the right, left, or both hepatic lobes and a total of 150 MBq 99mTc-HSAM (B20, ROTOP Pharmaka AG, Dresden, Germany) was injected from the
e217
defined microcatheter positions. Subsequent anterioreposterior planar gamma camera images of the trunk were recorded and after defining regions of interest for the lungs and the liver, the hepatopulmonary lung shunt fraction was calculated dividing the total lung count by the sum of the lung and liver count.21 Furthermore, combined single-photon emission computed tomography/computed tomography (SPECT/CT) analysis was performed to exclude any extrahepatic tracer accumulation.19,22,23
SIRT with 90-yttrium Therapeutic DSA for 90Y administration (TheraSphereÔ, BTG, Hertfordshire, United Kingdom) was performed in the same way as the pretreatment DSA. Initially, diagnostic DSA was carried out to check for impermeability of the previously coil embolized GDA and for potential newly apparent or reopened HIC. If HIC were detected, a reattempt to occlude the HICs using permanent coiling was undertaken followed by repeat 99mTc-HSAM. If this was not feasible, the microcatheter position was changed for 90Y administration in order to allow for a safe distance between the injection site and the HIC, for the most part followed by repeat 99mTcHSAM. However, the catheter tip was never positioned more proximally than the position that had been demonstrated to be safe by the 99mTc-HSAM SPECT/CT. If microcatheter repositioning was not feasible due to the peripheral localization of HIC, SIRT was considered as unsafe and was cancelled.
Follow-up Clinical symptoms such as dyspepsia, acid regurgitation, or abdominal pain were assessed directly after DSA and in clinical follow-up visits. Patients were discharged 48 h after 90 Y administration and had been strictly instructed to contact the hospital in case of any adverse event.
Results In 86 of 606 patients (14%, 95% CI: 12e17%), the GDA was initially occluded. Twenty-two of these 86 patients did neither undergo SIRT nor further SIRT evaluation due to clinical deterioration (n ¼ 9), interim liver transplantation (n ¼ 1), insufficient tumoural 99mTc-HSAM accumulation (n ¼ 4), a predicted lung dose exceeding 30 Gy (n ¼ 4), preference for other therapeutic options such as edotreotide treatment in hepatic metastasis of neuroendocrine tumours (n ¼ 3), or final refusal of SIRT by the patient (n ¼ 1). Hence, 64 patients were further scheduled for SIRT (n ¼ 2) or received SIRT (n ¼ 62). The median time interval between initial DSA, including GDA coiling, and subsequent DSA with SIRT and Re-HSA scan was 35 days (range 2e76 days). The median time interval between initial DSA and SIRT was 36 days (range 15e115 days). These long time intervals were caused by several repeated 99mTc-HSAM SPECT/CT examinations due to gastrointestinal 99mTc-HSAM accumulation (n ¼ 11), administration of sorafenib
e218
J. Schelhorn et al. / Clinical Radiology 69 (2014) e216ee222
Figure 1 Flowchart: SIRT evaluation of all 606 patients.
(Nexavar, Bayer AG, Leverkusen, Germany) for lung shunt reduction (n ¼ 1), one failed SIRT due to microcatheter occlusion during 90Y administration (n ¼ 1), and interim surgical resection of the HIC (n ¼ 1). Of the 62 patients who finally received SIRT, 50 had a lobar approach with 90Y administration into the right, left, or both hepatic arteries and only 12 a whole-liver approach with 90Y administration into the main hepatic artery. In 36 of 64 patients (56%), the therapeutic DSA did not reveal any newly apparent or reopened HICs, resulting in a straightforward SIRT. All 36 patients tolerated SIRT well. In 28 of 64 patients (44%, 95% CI: 32e56%), new or reopened HICs were detected based on DSA (Fig 1). In 21 of 28 patients (75%), these HICs were located at the proximal stump of the occluded GDA or at the proximal common hepatic artery (Fig 2). In 15 of these 21 patients, the HIC did not interfere
with microcatheter positioning for 90Y administration due to a sufficiently safe distance between the HIC and the 90Y injection site. However, in six of 21 patients a more distal microcatheter position had to be chosen to avoid nontargeted microsphere diversion during SIRT. In all 21 patients, SIRT was performed without any complications. In seven of the 28 patients with HICs (25%), the HICs were detected in the periphery of the hepatic arterial bed. In these patients, HICs arose from branches of the right (n ¼ 4), the left (n ¼ 2), or both hepatic arteries (n ¼ 1). In all seven patients, the newly apparent HICs were too small for probing and coil embolization. In four of the seven patients, a more distal microcatheter positioning was achievable; hence, SIRT could be safely performed (Fig 3). In three out of these seven patients, neither coil embolization nor a more distal microcatheter positioning was feasible. One of these patients was excluded from SIRT without any repeat 99mTc-HSAM administration due to HICs (Fig 4). In two other patients, the repeated 99mTc-HSAM administration confirmed relevant hepato-intestinal shunting, and therefore, SIRT was considered unsafe and was primarily abandoned. Extraordinarily, in one of these three patients, the interdisciplinary tumour team opted for surgical removal of the HIC. After this invasive surgical SIRT preparation, a repeated pretreatment DSA showed no remaining HIC or gastrointestinal 99mTc-HSAM accumulation (Fig 5). Thus, SIRT could be performed and was tolerated well in this patient. SIRT could not be performed in the remaining two patients.
Discussion GDA coil embolization prior to SIRT is commonly performed in many centres. However, in the present study, recruitment of preformed HICs that were not relevantly
Figure 2 Initial hepaticography visualising a patent GDA (a). After GDA coil embolization a reopened side branch on the GDA stump (considered as a proximal HIC) was detected during DSA (b). In cases like these, SIRT can be safely performed with a more distal microcatheter position.
J. Schelhorn et al. / Clinical Radiology 69 (2014) e216ee222
e219
Figure 3 In the initial celiacography (a) and hepaticography (b) a patent GDA is visible without any other detectable HICs. After GDA occlusion peripheral HICs arising from the right hepatic artery were detected (c). SIRT was still possible because a more distal microcatheter position was achievable (d).
perfused previously and reopening of coiled or even newly developed HICs were found in 44% of patients after GDA occlusion. In the majority of cases, SIRT was still feasible after recoiling or modification of the microcatheter position. However, in 5% of patients, this was not possible and SIRT had to be abandoned. Hence, coil embolization of the GDA with consecutively developed or newly perfused HICs can permanently exclude patients from SIRT. Therefore, a primary lobar or segmental SIRT approach is preferred and GDA coiling avoided to eliminate the risk of the rare development of peripheral HICs. Furthermore, as a future perspective, with currently developed anti-reflux devices, one may even choose a whole-liver SIRT approach with a relatively proximal microcatheter position without the need for GDA coiling to avoid any risk of reopening or recruitment of HICs (Fischman A, Arepally A, Sze D et al. Radioembolisation without prophylactic coil embolization
of patent proximal extrahepatic vasculature: use of an antireflux infusion system. In: Cirse 2013. Cardiovasc Intervent Radiol. 2013 Sep;36(3) Supplement: S221.) It is crucial to prevent 90Y distribution into small gastrointestinal vessels as this may lead to non-healing gastrointestinal ulcers.1 Currently, rates of radiationinduced gastritis and gastrointestinal ulcerations of 0.7e4.8% in SIRT have been reported.18,24,25 These ulcerations are predominantly located in the stomach and duodenum on the serosal surface and can be refractory to medical therapy. They may lead to gastrointestinal bleeding, bowel obstruction, or even perforation, and in severe cases surgical therapy is required.26 To overcome this problem, different strategies exist. Either the critical vessels can be occluded or a more peripheral microcatheter position for 90Y administration can be chosen. However, the latter strategy may result in the need of numerous 90Y
e220
J. Schelhorn et al. / Clinical Radiology 69 (2014) e216ee222
Figure 4 After GDA coil embolization newly apparent peripheral HICs were detected in DSA resulting in the impracticality of SIRT: primary coeliacography with patent GDA (a), in the repeated DSA multiple newly visible HIC were seen in the hepaticography (b) and after separate probing of common (c), right (d) and left hepatic artery (e).
injections, which can be time-consuming, technically challenging, and cumbersome. Therefore, some authors propagate the occlusion of most gastrointestinal shunt vessels prior to SIRT.1,15,19,27 This approach was chosen by Abdelmaksoud et al.20 who investigated 122 patients undergoing whole-liver SIRT after endovascular skeletonization of the hepatic artery. Embolization of all hepatico-enteric vessels was performed in the pretreatment DSA by this group. Vessel occlusion was verified by C-arm computed tomography (CACT) and 99mtechnetium macro-aggregated albumin (99mTc-MAA) scintigraphy. During the following treatment session, DSA and CACT were repeated to investigate for new or reopened HICs. In 42 patients (34%), Abdelmaksoud et al. found HICs requiring recoiling. Despite re-embolization, three patients developed gastric or duodenal ulcerations. The rate of newly apparent or reopened HICs reported by this group is comparable to the number of HIC in the present cohort. However, in the present study different clinical consequences were drawn from these findings. Owing to safety reasons, three patients with peripheral HICs were excluded from SIRT. However, the majority of the present patients received SIRT and none developed any gastrointestinal adverse events, which is very important in the palliative setting of SIRT. The above-described facts underline the complex situation that can be found after coiling of hepato-intestinal shunt vessels. Although the majority of patients do not face any problems after GDA occlusion, patients with new or reopened HICs should be triaged into groups of (a) re-embolization, (b) change of microcatheter position, and (c) exclusion from SIRT. Clearly, there are no strict guidelines for this triage and patients with HICs should be discussed individually.
Petroziello et al.28 described that after pretreatment side-branch embolization, eight of their 56 patients (14%) presented with recanalized or newly developed HICs and that seven out of the 110 primarily coiled vessels (6%) had newly developed collaterals.28 Patients with reopened or new HIC were treated, where possible, by re-embolization or a more distal microcatheter position. In one patient, SIRT was not performed for safety reasons. Compared with the present results and the findings of Abdelmaksoud et al., the number of newly apparent or reopened collaterals described by Petroziello et al. is much lower. One explanation could be that in the present study only coil embolization of the GDA was analysed. It is conceivable that after occlusion of a large vessel, the haemodynamic changes are more prone to lead to new or reopened HICs than after occlusion of smaller vessels such as the right gastric artery or even smaller accessory arteries as described by Petroziello et al. Most recently, Enriquez et al.29 investigated predisposing technical factors for GDA recanalization after coil embolization. One hundred and forty-two patients scheduled for either radioembolization or hepatic arterial chemotherapy were enrolled. In all subjects, the GDA was occluded using fibred coils. Different factors, including length of the coil pack, distance between GDA origin and coils, and platelet count, were analysed regarding the impact on GDA recanalization. Recanalization was undertaken in 20% of the patients. The only predisposing factor for recanalization was the distance between the GDA origin and the coil: the further the coil was from the origin, the more likely the GDA was recanalized. The other factors analysed did not have any impact on the recanalization rate. Again, the number of
J. Schelhorn et al. / Clinical Radiology 69 (2014) e216ee222
e221
Figure 5 The patent GDA (a) was initially embolized using coils (b). Afterwards, newly visible peripheral HICs were detected (c, d) and it was only after surgical removal of these HICs (e, f) that no more gastrointestinal 99mTc-HSAM accumulation was detected, and SIRT could finally be performed.
patients (approximately 20%) with recanalization is not high, but these patients require recoiling or a more distal microcatheter position, often resulting in a segmental approach. However, Enriquez did not focus on the location of the HICs and did not distinguish between proximal and peripheral HICs, which the present authors consider more critical because they may render even lobar or segmental SIRT impossible. These peripheral HIC were found in 11% of the present patients after GDA occlusion.
The present study is not without limitations. First, the diagnostic DSA was performed by different interventional radiologists. However, the procedure for SIRT preparation is standardized and all images were re-analysed for this study. As a further limitation, only coils were used for GDA occlusion. Other techniques, including the combination of coils and gelfoam or Amplatzer plugs, may result in a different incidence of HICs. Furthermore, this was a retrospective study. Of course, it would be favourable to perform
e222
J. Schelhorn et al. / Clinical Radiology 69 (2014) e216ee222
a prospective trial comparing the outcome of two patient groups with and without protective embolization of the GDA prior to SIRT. In summary, a lobar or segmental SIRT instead of a whole-liver approach and avoidance of GDA coiling are recommended to reduce the risk of peripheral HIC development.
References 1. Salem R, Thurston KG. Radioembolization with 90-yttrium microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies. Part 2: special topics. J Vasc Interv Radiol 2006;17:1425e39. 2. Salem R, Thurston KG. Radioembolization with yttrium-90 microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies. Part 3: comprehensive literature review and future direction. J Vasc Interv Radiol 2006;17:1571e93. 3. Salem R, Thurston KG. Radioembolization with 90-yttrium microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies. Part 1: technical and methodologic considerations. J Vasc Interv Radiol 2006;17:1251e78. 4. Salem R, Lewandowski RJ, Atassi B, et al. Treatment of unresectable hepatocellular carcinoma with use of 90Y microspheres (TheraSphere): safety, tumor response, and survival. J Vasc Interv Radiol 2005; 16:1627e39. 5. Salem R, Lewandowski RJ, Sato KT, et al. Technical aspects of radioembolization with 90Y microspheres. Tech Vasc Interv Radiol 2007;10:12e29. 6. Lewandowski RJ, Sato KT, Atassi B, et al. Radioembolization with 90Y microspheres: angiographic and technical considerations. Cardiovasc Intervent Radiol 2007;30:571e92. 7. Powerski MJ, Scheurig-Munkler C, Banzer J, et al. Clinical practice in radioembolization of hepatic malignancies: a survey among interventional centers in Europe. Eur J Radiol 2012;81:e804e11. 8. Wybranski C, Mohnike K, Ricke J. Minimally invasive tumor ablation in the liver. Anasthesiol Intensivmed Notfallmed Schmerzther 2009; 44(670):7. quiz 679. 9. Dudeck O, Zeile M, Wybranski C, et al. Early prediction of anticancer effects with diffusion-weighted MR imaging in patients with colorectal liver metastases following selective internal radiotherapy. Eur Radiol 2010;20:2699e706. 10. Mazzaferro V, Sposito C, Bhoori S, et al. Yttrium-90 radioembolization for intermediate-advanced hepatocellular carcinoma: a phase 2 study. Hepatology 2013;57:1826e37. 11. Sangro B, Carpanese L, Cianni R, et al. Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation. Hepatology 2011;54:868e78. 12. Salem R, Lewandowski RJ, Mulcahy MF, et al. Radioembolization for hepatocellular carcinoma using yttrium-90 microspheres: a comprehensive report of long-term outcomes. Gastroenterology 2010;138:52e64. 13. Hilgard P, Hamami M, Fouly AE, et al. Radioembolization with yttrium90 glass microspheres in hepatocellular carcinoma: European experience on safety and long-term survival. Hepatology 2010;52:1741e9.
14. Grober OS, Nultsch M, Laatz K, et al. Radioembolization with Y-labeled microspheres: post-therapeutic therapy validation with Bremsstrahlung-SPECT. Z Med Phys 2011;21:274e80. 15. Paprottka PM, Jakobs TF, Reiser MF, et al. Practical vascular anatomy in the preparation of radioembolization. Cardiovasc Intervent Radiol 2012;35:454e62. 16. Pech M, Kraetsch A, Wieners G, et al. Embolization of the gastroduodenal artery before selective internal radiotherapy: a prospectively randomized trial comparing platinum-fibered microcoils with the Amplatzer Vascular Plug II. Cardiovasc Intervent Radiol 2009;32: 455e61. 17. Dudeck O, Bulla K, Wieners G, et al. Embolization of the gastroduodenal artery before selective internal radiotherapy: a prospectively randomized trial comparing standard pushable coils with fibered interlock detachable coils. Cardiovasc Intervent Radiol 2011;34:74e80. 18. Naymagon S, Warner RR, Patel K, et al. Gastroduodenal ulceration associated with radioembolization for the treatment of hepatic tumors: an institutional experience and review of the literature. Dig Dis Sci 2010;55:2450e8. 19. Kennedy A, Nag S, Salem R, et al. Recommendations for radioembolization of hepatic malignancies using yttrium-90 microsphere brachytherapy: a consensus panel report from the radioembolization brachytherapy oncology consortium. Int J Radiat Oncol Biol Phys 2007;68:13e23. 20. Abdelmaksoud MH, Hwang GL, Louie JD, et al. Development of new hepaticoenteric collateral pathways after hepatic arterial skeletonization in preparation for yttrium-90 radioembolization. J Vasc Interv Radiol 2010;21:1385e95. 21. Dezarn WA, Cessna JT, DeWerd LA, et al. Recommendations of the American Association of Physicists in Medicine on dosimetry, imaging, and quality assurance procedures for 90Y microsphere brachytherapy in the treatment of hepatic malignancies. Med Phys 2011;38:4824e45. 22. Hamami ME, Poeppel TD, Muller S, et al. SPECT/CT with 99mTc-MAA in radioembolization with 90Y microspheres in patients with hepatocellular cancer. J Nucl Med 2009;50:688e92. 23. Ahmadzadehfar H, Sabet A, Muckle M, et al. 99mTc-MAA/90Y-Bremsstrahlung SPECT/CT after simultaneous Tc-MAA/90Y-microsphere injection for immediate treatment monitoring and further therapy planning for radioembolization. Eur J Nucl Med Mol Imaging 2011;38:1281e8. 24. Kennedy AS, McNeillie P, Dezarn WA, et al. Treatment parameters and outcome in 680 treatments of internal radiation with resin 90Y-microspheres for unresectable hepatic tumors. Int J Radiat Oncol Biol Phys 2009;74:1494e500. 25. Sato KT, Lewandowski RJ, Mulcahy MF, et al. Unresectable chemorefractory liver metastases: radioembolization with 90Y microspheresdsafety, efficacy, and survival. Radiology 2008;247:507e15. 26. Collins J, Salem R. Hepatic radioembolization complicated by gastrointestinal ulceration. Semin Intervent Radiol 2011;28:240e5. 27. Liu DM, Salem R, Bui JT, et al. Angiographic considerations in patients undergoing liver-directed therapy. J Vasc Interv Radiol 2005;16:911e35. 28. Petroziello MF, McCann JW, Gonsalves CF, et al. Side-branch embolization before 90Y radioembolization: rate of recanalization and new collateral development. AJR Am J Roentgenol 2011;197:W169e74. 29. Enriquez J, Javadi S, Murthy R, et al. Gastroduodenal artery recanalization after transcatheter fibered coil embolization for prevention of hepaticoenteric flow: incidence and predisposing technical factors in 142 patients. Acta Radiol 2013;54:790e4.