Jose I Bilbao

Clínica Universidad de Navarra, Madrid, Madrid, Spain

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Publications (12)60.14 Total impact

  • Article: Reply to: "Pre-therapeutic dosimetry evaluation and selective internal radiation therapy of hepatocellular carcinoma using yttrium-90-loaded microspheres"
    Journal of Hepatology 01/2013; · 9.26 Impact Factor
  • Article: Prognostic factors and prevention of radioembolization-induced liver disease.
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    ABSTRACT: Radioembolization (RE)-induced liver disease (REILD) has been defined as jaundice and ascites appearing 1 to 2 months after RE in the absence of tumor progression or bile duct occlusion. Our aims were to study the incidence of REILD in a large cohort of patients and the impact of a series of changes introduced in the processes of treatment design, activity calculation and the routine use of ursodeoxycholic acid and low-dose steroids (modified protocol). Between 2003 and 2011, 260 patients with liver tumors treated by RE were studied (standard protocol: 75, modified protocol: 185). REILD appeared only in patients with cirrhosis or in non-cirrhotic patients exposed to systemic chemotherapy prior to RE. Globally, the incidence of REILD was reduced in the modified protocol group from 22.7% to 5.4% and the incidence of severe REILD from 13.3% to 2.2% (p=0.000). Treatment efficacy was not jeopardized since 3-month disease control rates were virtually identical in both groups (66.7% and 67.2%, p=0.93). Exposure to chemotherapy in the 2-month period following RE, and being treated by the standard protocol were independent predictors of REILD among non-cirrhotic patients. In cirrhotics, the presence of a small liver (total volume <1.5 L), an abnormal bilirubin (> 1.2 mg/dL), and treatment in a selective fashion were independently associated to REILD. Conclusion: REILD is an uncommon but relevant complication that appears when liver tissue primed by cirrhosis or prior and subsequent chemotherapy is exposed to the radiation delivered by radioactive microspheres. We have designed a comprehensive treatment protocol that reduces the frequency and the severity of REILD. (HEPATOLOGY 2012.).
    Hepatology 12/2012; · 11.66 Impact Factor
  • Article: Radioembolization for hepatocellular carcinoma.
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    ABSTRACT: Radioembolization is a form of brachytherapy in which intra-arterially injected (90)Y-loaded microspheres serve as sources for internal radiation purposes. It produces average disease control rates above 80% and is usually very well tolerated. Main complications do not result from the microembolic effect, even in patients with portal vein occlusion, but rather from an excessive irradiation of non-target tissues including the liver. All the evidence that support the use of radioembolization in HCC is based on retrospective series or non-controlled prospective studies. However, reliable data can be obtained from the literature, particularly since the recent publication of large series accounting for nearly 700 patients. When compared to the standard of care for the intermediate and advanced stages (transarterial embolization and sorafenib), radioembolization consistently provides similar survival rates. Two indications seem particularly appealing in the boundaries of these stages for first-line radioembolization. First, the treatment of patients straddling between the intermediate and advanced stages (intermediate patients with bulky or bilobar disease that are considered poor candidates for TACE, and advanced patients with solitary tumors invading a segmental or lobar branch of the portal vein). Second, the treatment of patients that are slightly above the criteria for resection, ablation or transplantation, for which downstaging could open the door for a radical approach. Radioembolization can also be used to treat patients progressing to TACE or sorafenib. With a number of clinical trials underway, the available evidence shows that it adds a significant value to the therapeutic weaponry against HCC of tertiary care centers dealing with this major cancer problem.
    Journal of Hepatology 08/2011; 56(2):464-73. · 9.26 Impact Factor
  • Article: Radioembolization with use of yttrium-90 resin microspheres in patients with hepatocellular carcinoma and portal vein thrombosis.
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    ABSTRACT: Intraarterial delivery of yttrium-90 ((90)Y)-bound microspheres (ie, radioembolization) is a promising treatment for hepatocellular carcinoma (HCC). An early concern was the "embolic" nature of the microspheres, and their potential to reduce hepatic arterial blood flow in patients with compromised portal blood flow secondary to portal vein thrombosis/occlusion (PVT). In this situation, the risk of liver failure could be enhanced, particularly in patients with cirrhosis who have increased hepatic arterial blood flow. This retrospective analysis was undertaken to assess the safety and clinical benefits of radioembolization with (90)Y resin microspheres in HCC with branch or main PVT. A total of 25 patients presenting with unresectable HCC and compromised portal flow received segmental, lobar, or whole-liver infusion of (90)Y resin microspheres. For the analysis of tumor response, changes in target lesions, appearance of new lesions, and changes in portal vein thrombus were studied. Controlled disease was defined by absence of progression in all these components. Globally, controlled disease was achieved in 66.7% of patients at 2 months and 50% of patients at 6 months. No significant changes were observed in liver-related toxicities according to Common Toxicity Criteria (version 3.0) at 1 and 2 months after treatment. Median survival time was 10 months (95% CI, 6.6-13.3 months). Radioembolization of unresectable HCC and branch or main PVT with (90)Y resin microspheres was associated with minimal toxicity and a favorable median survival time. Further prospective studies are warranted to validate the findings in this clinically challenging patient population.
    Journal of vascular and interventional radiology: JVIR 08/2010; 21(8):1205-12. · 1.81 Impact Factor
  • Article: Treatment of hepatocellular carcinoma by radioembolization using 90Y microspheres.
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    ABSTRACT: The use of external beam radiation therapy for primary treatment of hepatocellular carcinoma (HCC) has been limited by the low radiation tolerance of the non-tumoral liver. However, technical advances allowing partial liver volume external irradiation have resulted in consistently high response rates. Internal radiation therapy, also called (90)Y radioembolization ((90)Y-RE), consists in delivering implantable microspheres labeled with (90)Y into the arteries that feed liver tumors in order to provide a high dose of radiation to tumor nodules irrespective of their number, size and location, while preserving the non-tumoral liver tissue from receiving a harmful level of radiation. Among patients with HCC, (90)Y-RE is used for those that have a preserved liver function and unresectable tumors that cannot be treated with percutaneous ablation. Although (90)Y-RE is by and large well tolerated, it may produce relevant toxic effects as a result of radiation of non-target organs including cholecystitis, gastrointestinal ulceration, pneumonitis, and most importantly, liver toxicity. A significant effect on tumor growth in the treated lesions is consistently observed with disease control rates in excess of 80%. Also, (90)Y-RE may allow downstaging large or multiple lesions to radical treatments with curative intent. When compared with the survival of HCC patients in advanced stage either not treated or treated with ineffective systemic agents, survival after (90)Y-RE is encouraging and warrants future clinical trials. Clinical research in combining the cytotoxic effect of (90)Y with the cytostatic mechanism of targeted therapies is currently in progress and will provide valuable safety and toxicity data that may translate into improved clinical outcome and overall survival.
    Digestive Diseases 02/2009; 27(2):164-9. · 2.37 Impact Factor
  • Article: Liver disease induced by radioembolization of liver tumors: description and possible risk factors.
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    ABSTRACT: To the authors' knowledge, liver damage after liver radioembolization with yttrium90-labeled microspheres has never been studied specifically. Using a complete set of data recorded prospectively among all patients without previous chronic liver disease treated by radioembolization at the authors' institution from September 2003 to July 2006, patterns of liver damage were identified and possible risk factors were analyzed. In all, 20% of patients developed a distinct clinical picture that appeared 4 to 8 weeks after treatment and was characterized by jaundice and ascites. Veno-occlusive disease was the histologic hallmark observed in the most severe cases. This form of sinusoidal obstruction syndrome was not observed among patients who never received chemotherapy or in those in whom a single hepatic lobe was treated. Relevant to treatment planning, a possible risk factor was a higher treatment dose in relation to the targeted liver volume. A transjugular intrahepatic stent shunt improved liver function in 2 patients with impending liver failure, although 1 of them eventually died from it. Radioembolization of liver tumors, particularly after antineoplastic chemotherapy, may result in an uncommon but potentially life-threatening form of hepatic sinusoidal obstruction syndrome that presents clinically with jaundice and ascites.
    Cancer 05/2008; 112(7):1538-46. · 4.77 Impact Factor
  • Article: Liver disease induced by radioembolization of liver tumors
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    ABSTRACT: BACKGROUND To the authors' knowledge, liver damage after liver radioembolization with yttrium90-labeled microspheres has never been studied specifically.METHODS Using a complete set of data recorded prospectively among all patients without previous chronic liver disease treated by radioembolization at the authors' institution from September 2003 to July 2006, patterns of liver damage were identified and possible risk factors were analyzed.RESULTSIn all, 20% of patients developed a distinct clinical picture that appeared 4 to 8 weeks after treatment and was characterized by jaundice and ascites. Veno-occlusive disease was the histologic hallmark observed in the most severe cases. This form of sinusoidal obstruction syndrome was not observed among patients who never received chemotherapy or in those in whom a single hepatic lobe was treated. Relevant to treatment planning, a possible risk factor was a higher treatment dose in relation to the targeted liver volume. A transjugular intrahepatic stent shunt improved liver function in 2 patients with impending liver failure, although 1 of them eventually died from it.CONCLUSIONS Radioembolization of liver tumors, particularly after antineoplastic chemotherapy, may result in an uncommon but potentially life-threatening form of hepatic sinusoidal obstruction syndrome that presents clinically with jaundice and ascites. Cancer 2008. © 2008 American Cancer Society.
    Cancer 03/2008; 112(7):1538 - 1546. · 4.77 Impact Factor
  • Article: Gastroduodenal injury after radioembolization of hepatic tumors.
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    ABSTRACT: Radioembolization is a new tool for the treatment of hepatic tumors that consists in the injection of biocompatible microspheres carrying radioisotopes into the hepatic artery or its branches. We have performed radioembolization in 78 patients with hepatic tumors using resin-based microspheres loaded with yttrium-90. All patients were previously evaluated to minimize the risk of hazardous irradiation to nontarget organs and to obtain the data needed for dose calculation. We report a complication found in three cases (3.8%) that consists of abdominal pain resulting from gastroduodenal lesions and that had a chronic, insidious course. Microscopically, microspheres were detected in the specimens obtained from all affected gastric areas. Since these gastroduodenal lesions do not appear when nonradiating microspheres are injected in animals, lesions are likely to be due to radiation and not to an ischemic effect of vascular occlusion by spheres. We believe that a pretreatment evaluation that includes a more thorough scrutiny of the hepatic vascularization in search of small collaterals connecting to the gastroduodenal tract can help prevent this awkward complication.
    The American Journal of Gastroenterology 07/2007; 102(6):1216-20. · 7.28 Impact Factor
  • Article: Radioembolization using 90Y-resin microspheres for patients with advanced hepatocellular carcinoma.
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    ABSTRACT: To investigate the antitumor effect of resin microspheres loaded with 90-yttrium against hepatocellular carcinoma and their safety in the setting of liver cirrhosis. Data from 24 consecutive patients with hepatocellular carcinoma (HCC) treated by radioembolization in the period from September 2003 to February 2005 were reviewed. Patients received no further antineoplastic therapy. A comprehensive evaluation was performed to prevent the risk of damage due to microsphere misplacing. Patients were discharged the day after microspheres injection. Serious liver toxicity observed among cirrhotic patients in a first period was subsequently prevented by modifying the selection criteria and the method for calculating the activity to be administered. Among 21 patients evaluable for response using Response Evaluation Criteria in Solid Tumors (RECIST) criteria, a reduction in size of target lesions was observed in all but 1 patient. When considering only target lesions, disease control rate and response rate were 100% and 23.8%, respectively. However, 43% of patients progressed in the liver in the form of new lesions appearing a median time of 3 months after radioembolization. Our experience in these series of patients indicates that radioembolization using resin microspheres has a significant antitumor effect against HCC and that using stringent selection criteria and conservative models for calculating the radiation activity to be administered, radioembolization can be performed safely even in cirrhotic patients.
    International Journal of Radiation OncologyBiologyPhysics 12/2006; 66(3):792-800. · 4.11 Impact Factor
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    Article: In vivo evaluation of a new embolic spherical particle (HepaSphere) in a kidney animal model.
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    ABSTRACT: HepaSphere is a new spherical embolic material developed in a dry state that absorbs fluids and adapts to the vessel wall, leaving no space between the particle and the arterial wall. The aim of this study was to elucidate the final in vivo size, deformation, final location, and main properties of the particles when reconstituted with two different contrast media (Iodixanol and Ioxaglate) in an animal model. Two sizes of "dry-state" particles (50-100 and 150-200 microm) were reconstituted using both ionic and nonionic contrast media. The mixture was used to partly embolize both kidneys in an animal model (14 pigs). The animals were sacrificed 4 weeks after the procedure and the samples processed. The final size of the particles was 230.2 +/- 62.5 microm for the 50- to 100-microm dry-state particles and 314.4 +/- 71 microm for the 150- to 200-microm dry-state particles. When the contrast medium (ionic versus nonionic) used for the reconstitution was studied to compare (Student's t-test) the final size of the particles, no differences were found (p > 0.05). The mean in vivo deformation for HepaSphere was 17.1% +/- 12.3%. No differences (p > 0.05) were found in the deformation of the particle regarding the dry-state size or the contrast medium (Mann-Whitney test). We conclude that HepaSphere is stable, occludes perfectly, and morphologically adapts to the vessel lumen of the arteries embolized. There is no recanalization of the arteries 4 weeks after embolization. Its final in vivo size is predictable and the particle has the same properties in terms of size and deformation with the two different contrast media (Iodixanol and Ioxaglate).
    CardioVascular and Interventional Radiology 31(2):367-76. · 2.09 Impact Factor
  • Article: Treatment of ureteroarterial fistulae with covered vascular endoprostheses and ureteral occlusion.
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    ABSTRACT: Ureteroarterial fistulae (UAFs) are a rare entity, often difficult to identify, and associated with a high mortality rate. This fact has been attributed to a delay in diagnosis and treatment. Five conditions that can predispose to the development of this uncommon entity have been described: prior pelvic surgery, prolonged ureteral stenting, radiation therapy, previous vascular surgery and vascular pathology. We present 4 patients with UAFs and at least three of the above-mentioned conditions. Ureteral ischemia and subsequent necrosis promote the formation of these fistulae. The constant pulsation of the iliac artery is transmitted to an already compromised ureter containing a stiff intraluminal foreign body, resulting in pressure necrosis, most likely where the ureter crosses the iliac artery. Cases were managed percutaneously with a combination of the deployment of a covered prosthesis and, when needed, with mechanical occlusion of the ureter. Hematuria stopped in all the patients with no evidence of immediate rebleeding. One patient presented a new episode of vaginal bleeding 13 months after endograft placement and ureteral embolization. Arteriography showed the presence of a hypogastric artery pseudoaneurysm that was occluded using coils. No new bleeding has occurred in this patient 12 months after the second embolization. At present all 4 patients are alive with follow-up periods of 5, 9, 11 and 25 months since the first procedure.
    CardioVascular and Interventional Radiology 28(2):159-63. · 2.09 Impact Factor
  • Article: A retrospective comparative analysis of the effect of Y90-radioembolization on the survival of patients with unresectable hepatocellular carcinoma.
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    ABSTRACT: to determine the impact of Y90-Radioembolization on survival when used as a first-line treatment for unresectable HCC. We retrospectively analyzed 35 consecutive patients with unresectable HCC who received 90Y-labeled resin microspheres as first-line treatment and compared their overall survival from the time of diagnosis with that of a cohort of 43 patients with unresectable HCC that were potential candidates for Y90-Radioembolization but had received conventional care due to unavailability or technical contraindications. Patients in both groups had a similar liver function and tumor burden. Median survival from diagnosis was significantly higher in the radioembolization group compared with controls (16 vs. 8 months; p < 0.05), even after adjusting for cirrhosis, multinodular disease, bilobar involvement or vascular invasion. In a multivariate analysis, treatment by radioembolization was the only prognostic factor independently associated with improved survival. In an intention-to-treat analysis, patients evaluated for radioembolization (finally treated or not) survived longer than controls (13 vs. 10 months; p < 0.05). Y90-Radioembolization is likely to improve survival among patients with unresectable HCC compared with conventional treatment. Further prospective studies are needed to evaluate the potential of this new treatment modality in unresectable HCC.
    Hepato-gastroenterology 56(96):1683-8. · 0.66 Impact Factor