Gastrointestinal Complications Associated with Hepatic Arterial Yttrium-90 Microsphere Therapy
2007; Elsevier BV; Volume: 18; Issue: 4 Linguagem: Inglês
10.1016/j.jvir.2007.02.002
ISSN1535-7732
AutoresRavi Murthy, Daniel B. Brown, Riad Salem, Steven G. Meranze, Douglas M. Coldwell, Sunil Krishnan, Rodolfo Núñez, Amit Habbu, David Liu, William A. Ross, Alan M. Cohen, Michael L. Censullo,
Tópico(s)Organ Transplantation Techniques and Outcomes
ResumoHepatic arterial therapy with yttrium-90 microspheres exploits the avenue provided by the neoplastic microvasculature to deliver high-energy, low-penetrating therapeutic doses of radiation. Variant hepatic arterial anatomy, collateral vessels, and changes in flow dynamics during treatment can affect particle dispersion and lead to nontarget particle distribution and subsequent gastrointestinal morbidity. Awareness of these variances and techniques to prevent gastrointestinal tract microsphere delivery is essential in mitigating this serious complication. Our aim is to increase the understanding of the role of various imaging and preventative techniques in minimizing this undesired effect. Hepatic arterial therapy with yttrium-90 microspheres exploits the avenue provided by the neoplastic microvasculature to deliver high-energy, low-penetrating therapeutic doses of radiation. Variant hepatic arterial anatomy, collateral vessels, and changes in flow dynamics during treatment can affect particle dispersion and lead to nontarget particle distribution and subsequent gastrointestinal morbidity. Awareness of these variances and techniques to prevent gastrointestinal tract microsphere delivery is essential in mitigating this serious complication. Our aim is to increase the understanding of the role of various imaging and preventative techniques in minimizing this undesired effect. YTTRIUM 90 (90Y) is produced by neutron bombardment of yttrium 89. 90Y has a half-life of 67.4 hours and emits characteristic high-energy beta particles (0.9 MeV) that have an average penetration of 2.5 mm in tissue. Hepatic arterial delivery of 90Y radioactive microspheres, also termed radioembolization, microsphere brachytherapy, or selective internal radiation therapy, has shown promising clinical results in the treatment of unresectable primary hepatocellular carcinoma and hepatic metastases from colorectal cancer. Microspheres containing 90Y and measuring between 20 and 40 μm are injected into the hepatic artery where they preferentially distribute and embolize within the hepatic tumoral vascular plexus by virtue of their diameter. Both commercially available microsphere devices for delivering 90Y, TheraSphere (MDS Nordion, Ottawa, Canada) and SIR-Spheres (Sirtex Medical, Sydney, Australia), have been used extensively in Australasia and Canada over the past two decades. Although 90Y is the active moiety for both devices, important differences influence device delivery (Table 1). Currently, SIR-Spheres (resin) are U.S. Food and Drug Administration (FDA) approved, in conjunction with intraarterial adjuvant fludarabine, for the treatment of hepatic metastases from colorectal adenocarcinoma, and TheraSphere (glass) is FDA approved for the treatment of initially unresectable hepatocellular carcinoma.Table 1Important Differences Between TheraSphere and SIR-SpheresCharacteristicTheraSphereSIR-SpheresCompositionGlassResinSpecific activity per microsphere (GBq)2,50050Specific gravity per microsphereHighLowAverage microspheres (million) per dose3–840–60Maximal prescribed dose (GBq)203Relative embolic potentialLowerHigherRelative pressure for infusionHigherLowerContrast injection during infusionNot possiblePossible Open table in a new tab Along with direct radiation effects, toxic effects specific to 90Y microsphere therapy have been well described, the most common of which are gastrointestinal. This is presumed to be caused by nontarget sphere distribution attributable to unrecognized variant or collateral circulation, as well as changes in flow dynamics during infusion. Information obtained during the 90Y microsphere treatment-planning process assists in avoiding or mitigating this serious toxic effect. Performing high-quality nonselective and selective arteriography of the celiac and superior mesenteric arterial distribution is the most important step in minimizing gastrointestinal toxicity. Carefully characterizing the hepatic arterial supply is essential because identifying these extrahepatic arteries is necessary for vascular exclusion as it is believed that gastrointestinal ulceration invariably results from microsphere diversion via extrahepatic arteries that supply the esophagus, duodenum, or gastric structures. These extrahepatic arteries include the gastroduodenal artery (GDA), right gastric artery (RGA), and retroduodenal artery; however, usually several small and variable unnamed arteries may be present, and recognition of these variants is important. To further complicate this issue, variance or altered morphology of both the hepatic and extrahepatic arteries frequently causes misperception and misidentification of these vessels on arteriography especially in the presence of neoplastic disease (1Liu D.M. Salem R. Bui J.T. et al.Angiographic considerations in patients undergoing liver-directed therapy.J Vasc Interv Radiol. 2005; 16: 911-935Abstract Full Text Full Text PDF PubMed Scopus (190) Google Scholar). As part of the pretreatment evaluation, approximately 5 mCi technetium (Tc99m) macroaggregated albumin (MAA) is injected into the hepatic artery. This determines the extent of any arteriovenous shunts but also acts as a microsphere surrogate and can help to identify any nontarget organs via the detection of extrahepatic abdominal scintigraphic activity. It is then assumed that diversion of the microspheres to the gastrointestinal tract occurred via patent arteries. The therapy-planning arteriogram must then be retrospectively reviewed to identify and exclude the culprit artery (or arteries) before the therapeutic 90Y microspheres are administered. Secondary emission Bremsstrahlung scans after delivery indirectly detect the distribution of the microspheres within and external to the liver. Once embolized, these microspheres are nonretrievable. To illustrate the role and pitfalls of various imaging techniques and interpretation, we present two cases of gastrointestinal ulceration after 90Y resin microsphere therapy and review the relevant imaging and literature. Ulcers after 90Y glass microsphere therapy have occurred, but the authors lacked access to similar illustrative cases suitable for publication. The institutional review boards of our respective institutions approved this retrospective study, and a waiver was granted for informed consent. A clinically occult rectal adenocarcinoma with synchronous bilobar hepatic metastases (stage IV) was detected during the assessment for myocardial infarction secondary to iron deficiency anemia in a 42-year-old male. The treatment plan called for liver-directed therapy with 90Y microspheres for intrahepatic disease progression and concurrent systemic chemotherapy. The GDA was coil-embolized via a microcatheter during the therapy-planning arteriogram. Tc99m MAA was administered into the common hepatic artery. Nuclear scintigraphy demonstrated hepatic and a small area of extrahepatic activity in the infrahepatic location. The extrahepatic activity was attributed to entrapment of the technetium Tc99m MAA within the static segment ("stump flow") of the embolized GDA (Fig 1a). The patient subsequently underwent right hepatic arterial infusion of 20.2 mCi of 90Y resin microspheres (SIR-Spheres) to treat the right lobe. Similarly, the left lobe was treated with 12.15 mCi of 90Y resin microspheres via the left hepatic artery at a separate catheterization 4 weeks later. The patient was discharged with a prescription for use of a daily proton pump inhibitor (PPI) after each treatment. Posttreatment Bremsstrahlung (secondary gamma emission) scans were not performed in either instance per institutional protocol. A few days after treatment of the left lobe, the patient developed persistent dyspepsia and emesis with oral intake despite increasing use of the PPI and the addition of sucralfate for gastrointestinal ulcer prophylaxis. An esophagogastroduodenoscopy revealed severe gastric antral ulcerations without evidence of Helicobacter pylori infection (Fig 1b). Endoscopic biopsy revealed characteristic microspheres in the gastric antral submucosa (Fig 1c). Retrospective review of the left hepatic arteriogram demonstrated an aberrant RGA that had been misperceived as a segmental branch of the left hepatic artery (Fig 1d) and, therefore, had not been embolized. Because of persistent emesis, enteral nutrition was transiently supplemented via a gastrojejunostomy catheter for 10 weeks after the second treatment, after which the ability to tolerate oral intake returned. A 67-year-old man underwent a right hemicolectomy for a moderately differentiated adenocarcinoma (T4N2M0, stage III). Adjuvant chemotherapy was discontinued after the patient experienced treatment-related toxic effects and the discovery of metachronous bilobar hepatic-only metastatic disease. He was referred for liver-directed therapy with 90Y microspheres. At therapy-planning arteriography, the proper hepatic artery was found to be relatively short, such that the origin of the GDA was adjacent to the origin of the right and left hepatic arteries. The GDA was embolized via a coaxially placed microcatheter with fibered microcoils. Injection of 4 mCi of Tc99m MAA delivered via the right hepatic artery revealed scintigraphic activity corresponding to the right lobe (Fig 2a). An arteriogram after embolization demonstrated complete focal occlusion of the GDA at the common hepatic artery origin (Fig 2b). Subsequently, the catheter was placed in the proper hepatic artery, through which 52.18 mCi of 90Y resin microspheres was infused with preservation of hepatopetal flow, thus allowing both lobes of the liver to be treated at a single session. Planar and single-photon emission computed tomography Bremsstrahlung scans were performed the next day to confirm hepatic deposition as per institutional protocol. They were initially interpreted as demonstrating no extrahepatic activity. The patient was prescribed PPI and sucralfate for gastrointestinal ulcer prophylaxis and was discharged from the hospital after an uneventful overnight observation. However, he subsequently developed progressive dyspepsia, nausea, and emesis. Esophagogastroduodenoscopy identified both gastric and duodenal ulcers, which were biopsied. The gastric biopsy demonstrated circular, hematoxyphilic structures that were consistent with the cross-sectional appearance of the microsphere (Fig 2c); Helicobacter pylori stained negative. Endoscopy 2 months later demonstrated healing of the ulcer after aggressive medical management. Retrospective review of the posttreatment planar Bremsstrahlung scintigraphic images demonstrated a curvilinear area of extrahepatic activity in an area corresponding with the gastric antrum (Fig 2d). Review of the arteriogram demonstrated an aberrant origin of the RGA from the left hepatic artery that had been misperceived on pretherapy angiography as a branch supplying the liver and, therefore, had not been embolized, allowing the 90Y microspheres to reach the stomach (Fig 2b). Because the Tc99m MAA was not delivered through the left hepatic artery, it did not traverse the RGA, and thus extrahepatic deposition of this surrogate agent was not created and therefore extrahepatic activity on the pretherapy nuclear scintigrams was not detected. Ionizing radiation is a recognized trigger for the development of clinically apparent changes in gastric mucosa, including mucosal fragility, thickening and congestion of the gastric folds, ulcerations, hemorrhagic gastritis, and perforation (2De Sagher L.I. Van den Heule B. Van Houtte P. Engelholm L. Balikdjan D. Bleiberg H. Endoscopic appearance of irradiated gastric mucosa.Endoscopy. 1979; 11: 163-165Crossref PubMed Scopus (7) Google Scholar). In clinical use, the tolerance of the stomach to radiation has been best described in patients with Hodgkin disease (3Cosset J.M. Henry-Amar M. Burgers J.M. et al.Late radiation injuries of the gastrointestinal tract in the H2 and H5 EORTC Hodgkin's disease trials: emphasis on the role of exploratory laparotomy and fractionation.Radiother Oncol. 1988; 13: 61-68Abstract Full Text PDF PubMed Scopus (48) Google Scholar). In this large report of radiation-induced gastrointestinal complications, among 516 patients treated to 40 Gy with infradiaphragmatic radiation fields that incidentally encompassed the stomach, 36 (7%) developed late gastrointestinal radiation toxic effects. Twenty-five (5%) patients presented with gastric or duodenal ulcers, two with severe gastritis, six with small bowel obstruction or perforation, and three with an ulcer and bowel obstruction. There was a statistically significant difference in the rate of these complications based on radiation fractionation. Patients receiving weekly doses of 2 Gy for 5 weeks, 2.5 Gy for 4 weeks, or 3.3 Gy for 3 weeks had complication rates of 4%, 9%, or 22%, respectively. The literature has numerous reports of gastrointestinal complications after the transhepatic arterial delivery of beta radiation–emitting 90Y microspheres (Table 2). Similar gastrointestinal toxic effects from hepatic chemoembolization (4Hirakawa M. Iida M. Aoyagi K. Matsui T. Akagi K. Fujishima M. Gastroduodenal lesions after transcatheter arterial chemo-embolization in patients with hepatocellular carcinoma.Am J Gastroenterol. 1988; 83: 837-840PubMed Google Scholar) and hepatic artery chemotherapy infusion (5Kemeny N. Daly J. Oderman P. et al.Hepatic artery pump infusion: toxicity and results in patients with metastatic colorectal carcinoma.J Clin Oncol. 1984; 2: 595-600Crossref PubMed Scopus (144) Google Scholar) are known to occur. An increased incidence of gastrointestinal complications has been shown to be associated with pretherapy extrahepatic activity detected on nuclear scintigraphy after the hepatic arterial injection of Tc99m MAA (6Bledin A. Kantarjian H. Kim E. et al.99mTc-labeled macroaggregated albumin in intrahepatic arterial chemotherapy.AJR Am J Roentgenol. 1982; 139: 711-715Crossref PubMed Scopus (44) Google Scholar). When hepatic artery chemotherapy infusion is performed, the detection of such extrahepatic perfusion and its subsequent reduction by ligature or embolization of the feeding vessels is described (7Inaba Y. Arai Y. Matsueda K. Takeuchi Y. Aramaki T. Right gastric artery embolization to prevent acute gastric mucosal lesions in patients undergoing repeat hepatic arterial infusion chemotherapy.J Vasc Interv Radiol. 2001; 12: 957-963Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar). When employing 90Y microspheres, the ischemic effect of embolization combined with the nonmigratory focal radiation dose is believed to increase the risk of an ulcer above that which would be expected with radiation or nonradioactive microspheres alone. In most published series, after microsphere implantation, patients developed abdominal symptoms such as acute and delayed abdominal pain, nausea, vomiting, and anorexia. The source of these symptoms may not be solely gastrointestinal in origin because pancreatitis and cholecystitis, which are also known to occur after this therapy, can produce an indistinguishable constellation of clinical findings (8Salem R. Thurston K.G. Radioembolization with 90yttrium microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies: part 2: special topics.J Vasc Interv Radiol. 2006; 17: 1425-1439Abstract Full Text Full Text PDF PubMed Scopus (170) Google Scholar, 9Thamboo T. Tan K.B. Wang S.C. Salto-Tellez M. Extra-hepatic embolisation of Y-90 microspheres from selective internal radiation therapy (SIRT) of the liver.Pathology. 2003; 35: 351-353PubMed Google Scholar, 10Carr B. Hepatic arterial 90yttrium glass microspheres (Therasphere) for unresectable hepatocellular carcinoma: interim safety and survival data on 65 patients.Liver Transpl. 2004; 10: S107-S110Crossref PubMed Scopus (216) Google Scholar, 11Salem R. Lewandowski R. Roberts C. et al.Use of yttrium-90 glass microspheres (TheraSphere) for the treatment of unresectable hepatocellular carcinoma in patients with portal vein thrombosis.J Vasc Interv Radiol. 2004; 15: 335-345Abstract Full Text Full Text PDF PubMed Scopus (167) Google Scholar, 12Liu M.D. Uaje M.B. Al-Ghazi M.S. et al.Use of yttrium-90 TheraSphere for the treatment of unresectable hepatocellular carcinoma.Am Surg. 2004; 70: 947-953PubMed Google Scholar, 13Popperl G. Helmberger T. Munzing W. Schmid R. Jacobs T.F. Tatsch K. Selective internal radiation therapy with SIR-Spheres in patients with nonresectable liver tumors.Cancer Biother Radiopharm. 2005; 20: 200-208Crossref PubMed Scopus (82) Google Scholar)Table 2Gastrointestinal Complications Associated with 90Y Microsphere TherapyAuthorNo. of PatientsGI SymptomsUlcersBiopsy with DeviceSurgical Rx UlcerCarr (10Carr B. Hepatic arterial 90yttrium glass microspheres (Therasphere) for unresectable hepatocellular carcinoma: interim safety and survival data on 65 patients.Liver Transpl. 2004; 10: S107-S110Crossref PubMed Scopus (216) Google Scholar)659 (14%)0—0Salem (11Salem R. Lewandowski R. Roberts C. et al.Use of yttrium-90 glass microspheres (TheraSphere) for the treatment of unresectable hepatocellular carcinoma in patients with portal vein thrombosis.J Vasc Interv Radiol. 2004; 15: 335-345Abstract Full Text Full Text PDF PubMed Scopus (167) Google Scholar)153 (20%)0—0Liu (12Liu M.D. Uaje M.B. Al-Ghazi M.S. et al.Use of yttrium-90 TheraSphere for the treatment of unresectable hepatocellular carcinoma.Am Surg. 2004; 70: 947-953PubMed Google Scholar)11R0—0Popperl (13Popperl G. Helmberger T. Munzing W. Schmid R. Jacobs T.F. Tatsch K. Selective internal radiation therapy with SIR-Spheres in patients with nonresectable liver tumors.Cancer Biother Radiopharm. 2005; 20: 200-208Crossref PubMed Scopus (82) Google Scholar)2320 (86%)1 (4%)NR0Kennedy (14Kennedy A.S. Coldwell D. Nutting C. Murthy R. Wertman Jr, D.E. Loehr S.P. et al.Resin 90Y-microsphere brachytherapy for unresectable colorectal liver metastases: modern USA experience.Int J Radiat Oncol Biol Phys. 2006; 65: 412-425Abstract Full Text Full Text PDF PubMed Scopus (292) Google Scholar)20852 (25%)12 (5%)NRNRStubbs (15Stubbs R.S. O'Brien I. Correia M.M. Selective internal radiation therapy with 90Y microspheres for colorectal liver metastases: single-centre experience with 100 patients.ANZ J Surg. 2006; 76: 696-703Crossref PubMed Scopus (88) Google Scholar)100R8 (8%)NRNRStubbs (16Stubbs R. Cannan R. Mitchell A. 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Goin J. et al.90Y microsphere (TheraSphere) treatment for unresectable colorectal cancer metastases of the liver: response to treatment at targeted doses of 135-150 Gy as measured by [18F]fluorodeoxyglucose positron emission tomography and computed tomographic imaging.J Vasc Interv Radiol. 2005; 16: 1641-1651Abstract Full Text Full Text PDF PubMed Scopus (133) Google Scholar)275 (19%)1NR1Herba (21Herba M. Thirlwell M. Radioembolization for hepatic metastases.Semin Oncol. 2002; 29: 152-159Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar)37NR3 (8%)10Andrews (22Andrews J. Walker S. Ackermann R. Cotton L. Ensminger W. Shapiro B. Hepatic radioembolization with yttrium-90 containing glass microspheres: preliminary results and clinical follow-up.J Nucl Med. 1994; 35: 1637-1644PubMed Google Scholar)24NR4 (17%)00Lim (23Lim L. Gibbs P. Yip D. et al.Prospective study of treatment with selective internal radiation therapy spheres in patients with unresectable primary or secondary hepatic malignancies.Intern Med J. 2005; 35: 222-227Crossref PubMed Scopus (57) Google Scholar)46R4 (8%)30Geschwind (24Geschwind J. Salem R. Carr B. et al.Yttrium-90 microspheres for the treatment of hepatocellular carcinoma.Gastroenterology. 2004; 127: S194-S205Abstract Full Text Full Text PDF PubMed Scopus (276) Google Scholar)8010 (13%)3 (3%)NR0Gray (25Gray B. Van Hazel G. Hope M. et al.Randomised trial of SIR-Spheres plus chemotherapy vs. chemotherapy alone for treating patients with liver metastases from primary large bowel cancer.Ann Oncol. 2001; 12: 1711-1720Crossref PubMed Scopus (432) Google Scholar)71R0—0Murthy (26Murthy R. Xiong H. 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Of the reported 1,140 patients in the literature where abdominal toxicities were reported, the median incidence of abdominal symptoms was six patients per reported series, and 25% (range, <1% to 45.5%) for the entire cohort. The median reported ulceration rate was 8% (range, 0% to 20%) with 6% (0.4% of the entire cohort) requiring surgical intervention. These results are skewed by reports with the highest incidence of ulcers being published in studies with a small number of patients suggesting a learning curve for the procedure coupled with the potential of duplication of the same patients with this complication in multiple publications by the same group. In a more recent report, the incidence of gastrointestinal complications and ulcers in more than 200 patients was 25% and 12%, respectively, in the largest modern multicenter U.S. experience to date; this included patients treated immediately after FDA approval of both devices. In this retrospective study, extrahepatic arterial embolization was performed at the discretion of the interventional radiologist (14Kennedy A.S. Coldwell D. Nutting C. Murthy R. Wertman Jr, D.E. Loehr S.P. et al.Resin 90Y-microsphere brachytherapy for unresectable colorectal liver metastases: modern USA experience.Int J Radiat Oncol Biol Phys. 2006; 65: 412-425Abstract Full Text Full Text PDF PubMed Scopus (292) Google Scholar). In a separate, large, single-center series from an experienced team in New Zealand, where delivery was predominately via implanted hepatic artery access devices, the ulcer rate was 8% with a disproportionately higher incidence after transcatheter-based delivery (15Stubbs R.S. O'Brien I. Correia M.M. Selective internal radiation therapy with 90Y microspheres for colorectal liver metastases: single-centre experience with 100 patients.ANZ J Surg. 2006; 76: 696-703Crossref PubMed Scopus (88) Google Scholar). In extreme cases, surgical intervention has been required for either nonhealing or bleeding ulcers (16Stubbs R. Cannan R. Mitchell A. Selective internal radiation therapy with 90yttrium microspheres for extensive colorectal liver metastases.J Gastrointest Surg. 2001; 5: 294-302Crossref PubMed Scopus (106) Google Scholar, 17Blanchard R. Morrow I. Sutherland J. Treatment of liver tumors with yttrium-90 microspheres alone.Can Assoc Radiol J. 1989; 40: 206-210PubMed Google Scholar, 18Shepherd F. Rotstein L. Houle S. Yip T. Paul K. Sniderman K. A phase I dose escalation trial of yttrium-90 microspheres in the treatment of primary hepatocellular carcinoma.Cancer. 1992; 70: 2250-2254Crossref PubMed Scopus (112) Google Scholar, 19Dancey J. Shepherd F. Paul K. Sniderman K. Houle S. Gabrys J. et al.Treatment of nonresectable hepatocellular carcinoma with intrahepatic 90Y-microspheres.J Nucl Med. 2000; 41: 1673-1681PubMed Google Scholar, 20Lewandowski R. Thurston K. Goin J. et al.90Y microsphere (TheraSphere) treatment for unresectable colorectal cancer metastases of the liver: response to treatment at targeted doses of 135-150 Gy as measured by [18F]fluorodeoxyglucose positron emission tomography and computed tomographic imaging.J Vasc Interv Radiol. 2005; 16: 1641-1651Abstract Full Text Full Text PDF PubMed Scopus (133) Google Scholar). A discordant number of these surgical cases were associated with alcohol abuse, preexisting peptic ulcer disease, and subsequent hepatic artery chemotherapy delivery (21Herba M. Thirlwell M. Radioembolization for hepatic metastases.Semin Oncol. 2002; 29: 152-159Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar, 22Andrews J. Walker S. Ackermann R. Cotton L. Ensminger W. Shapiro B. Hepatic radioembolization with yttrium-90 containing glass microspheres: preliminary results and clinical follow-up.J Nucl Med. 1994; 35: 1637-1644PubMed Google Scholar). Standardized reporting criteria, which would allow investigators and clinicians to directly compare outcomes, have been used in a minority of reports primarily because many of these antedated the requirement for such reporting. When applied, the systems used for monitoring toxicity data varied (19Dancey J. Shepherd F. Paul K. Sniderman K. Houle S. Gabrys J. et al.Treatment of nonresectable hepatocellular carcinoma with intrahepatic 90Y-microspheres.J Nucl Med. 2000; 41: 1673-1681PubMed Google Scholar, 23Lim L. Gibbs P. Yip D. et al.Prospective study of treatment with selective internal radiation therapy spheres in patients with unresectable primary or secondary hepatic malignancies.Intern Med J. 2005; 35: 222-227Crossref PubMed Scopus (57) Google Scholar, 24Geschwind J. Salem R. Carr B. et al.Yttrium-90 microspheres for the treatment of hepatocellular carcinoma.Gastroenterology. 2004; 127: S194-S205Abstract Full Text Full Text PDF PubMed Scopus (276) Google Scholar, 25Gray B. Van Hazel G. Hope M. et al.Randomised trial of SIR-Spheres plus chemotherapy vs. chemotherapy alone for treating patients with liver metastases from primary large bowel cancer.Ann Oncol. 2001; 12: 1711-1720Crossref PubMed Scopus (432) Google Scholar). Some reports do not list distinguishing details on the relative incidence and severity of abdominal symptoms despite the development of gastric ulcerations in their series (21Herba M. Thirlwell M. Radioembolization for hepatic metastases.Semin Oncol. 2002; 29: 152-159Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar, 22Andrews J. Walker S. Ackermann R. Cotton L. Ensminger W. Shapiro B. Hepatic radioembolization with yttrium-90 containing glass microspheres: preliminary results and clinical follow-up.J Nucl Med. 1994; 35: 1637-1644PubMed Google Scholar, 23Lim L. Gibbs P. Yip D. et al.Prospective study of treatment with selective internal radiation therapy spheres in patients with unresectable primary or secondary hepatic malignancies.Intern Med J. 2005; 35: 222-227Crossref PubMed Scopus (57) Google Scholar). Patients who developed gastrointestinal ulcerations were generally symptomatic, but even when symptoms were present, endoscopic evaluation was not pursued in all patien
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