AIM: To evaluate the long-term natural history of the gastroduodenal lesions secondary to extrahepatic embolization with Ytrium 90 (⁹⁰Y) spheres.

METHODS: From September 2003 to January 2012, 379 procedures of liver radioembolization (RE) using resin microspheres loaded with ⁹⁰Y were performed in our center. We have retrospectively compiled the data from 379 RE procedures performed in our center. We report a comprehensive clinical, analytical, endoscopic and histologic long-term follow-up of a series of patients who developed gastroduodenal lesions after the treatment.

RESULTS: Six patients (1.5%) developed gastrointestinal symptoms and had gastrointestinal lesions as shown by upper endoscopy in the next 12 wk after RE. The mean time between RE and the appearance of symptoms was 5 wk. Only one patient required endoscopic and surgical treatment. The incidence of gastrointestinal ulcerations was 3.75% (3/80) when only planar images were used for the pre-treatment evaluation. It was reduced to 1% (3/299) when single-photon emission computed tomography (SPECT) images were also performed. The symptoms that lasted for a longer time were nausea and vomiting, until 25 mo after the treatment.

CONCLUSION: All patients were free from severe symptoms at the end of follow-up. The routine use of SPECT has decreased the incidence of gastrointestinal lesions due to unintended deployment of ⁹⁰Y particles.

Radioembolization (RE) with microspheres embedded with Yttrium 90 (⁹⁰Y) is a therapeutic option for primary and secondary liver tumors. Prior to treatment, an angiography is performed to identify the hepatic vasculature and to mimic the actual procedure by injecting ⁹⁹Tc-radiolabeled macroaggregated albumin (99Tcm-MAA)[1]. During this procedure, guidelines recommend the embolization of the gastroduodenal artery, right gastric, and other extrahepatic arteries to isolate the hepatic circulation[2]. Unintended extrahepatic deployment of particles is a rare but well known complication of this procedure, that may result in cholescystitis[3], pancreatitis[4], radiation pneumonitis[5] and gastrointestinal ulcerations[6,7]. Radiation injury is likely to be the main pathogenical factor of these lesions[6]. However, although the small diameter of the particles (20-30 μm) does not induce a significant macroembolic effect, it has been shown in animal models that microspheres may sometimes aggregate and occlude small size vessels[8].

Radiation-induced gastrointestinal ulcerations may have a significant negative impact in quality of life due to decreased oral intake, pain or anemia, and the even need to perform gastric surgery has been described[9]. However, most case reports or series only describe the appearance and immediate consequences and very little is known about the long-term outcome of this complication. We describe for the first time a case series of six patients with gastrointestinal lesions secondary to RE and their clinical, endoscopic and histologic long-term follow-up.

From September 2003 to January 2012, 379 procedures of liver RE using resin microspheres loaded with ⁹⁰Y (SIR-Spheres, Sirtex Medical, Sidney, Australia) were performed in our center. Six patients (1.5%) developed gastrointestinal symptoms and had an upper endoscopy performed in the next 12 wk after the procedure that showed gastrointestinal lesions. Findings in the initial and the subsequent gastroduodenoscopies and their histopathologic studies were compiled retrospectively. Although the follow-up was not structured, at least two endoscopies were available from all but one patient. The maximum endoscopic follow-up time was 78 mo. We have gathered from the medical reports and thoroughly analyzed all clinical, analytical, endoscopic and histopathological findings.

RE is an accepted therapeutic technique for advanced primary and secondary liver tumors. It seems to be better tolerated than transarterial chemoembolization in terms of abdominal pain[10], length of hospital stay[11] and post-embolization symptoms[12]. Main complications do not result from the microembolic effect of the spheres, even in patients with portal vein occlusion, but rather from an excessive irradiation of non-target tissues, including the liver[13].

We describe in this case series an incidence of symptomatic gastroduodenal lesions after RE of 1.5% (6 out of 379 patients). Other authors have reported an incidence between 0% and 28%, with an average 4.8% calculated from the data previously published in 23 studies[7]. The two largest series of patients with secondary liver tumors from colorectal cancer or other malignancies reported rates of grade 3 gastrointestinal ulceration of 1% to 2%[14,15]. A higher incidence of 3.7% was found among 325 patients with hepatocellular carcinoma treated in 8 different European institutions[16].

A decrease in the incidence of gastroduodenal lesions was observed when SPECT images were used for evaluation the RE procedures compared with planar images. These data suggest that SPECT imaging is an important tool to minimize the risk of gastrointestinal adverse events secondary to RE treatment. Our results arise from a retrospective single center study. If they are further confirmed by other series, a possible change in the current guidelines could be considered in favor of the use of SPECT imaging.

In most patients (4 out of 6 patients, 66%) the spheres were injected from the common or proper hepatic artery. This site of injection leads to a greater chance of non-target embolization of the spheres in extrahepatic vessels. However, we have retrospectively reviewed all the angiographies and none of them showed collaterals or had extrahepatic deposits of MAA in the subsequent scans. In one of the patients treated by bilobar injection, a spasm in the left hepatic artery could have contributed to this complication.

In our case series, two patients were receiving combined concomitant treatment with the combination of oxaliplatin and 5-fluorouracil (FOLFOX) or gemcitabine (GEMOX). None of these drugs produce gastrointestinal lesions that could act as a confounding factor. In a literature search, we have found only one case of gastroduodenal ulceration with FOLFOX therapy and the patient was concurrently treated with Bevacizumab[17]. Saif et al[18] described a case of a patient treated with gemcitabine and warfarine who presented with gastrointestinal haemorrhage secondary to gastric and duodenal ulcers (with an international normalized ratio of 8.0). The lesions in our series are not likely to have been caused by these drugs, but we can not exclude a certain contribution.

The most common presenting symptoms in our series were abdominal pain, nausea/vomiting and anorexia. The intensity was usually mild and did not limit daily activities. Many drugs have been used, alone or in combination, demonstrating a slow but effective relieve of symptoms of this complication. However, more studies are needed to determine the best medical treatment. Only one patient required elective surgical treatment due to a late (> 1 year) duodenal stenosis. No urgent endoscopic or surgical treatment was performed. All but one patient are free of symptoms at the end of follow-up. All these data suggest that unintended gastrointestinal deployment of particles should be considered as a potential but transient cause of abdominal pain after the procedure. As shown in our series, the largest so far reported, a conservative approach must be considered as the primary treatment option. Nevertheless, the long-standing duration of symptoms (maximum 25 mo) in association with other factors (anemia, tumor progression and other comorbidities) certainly impacts the quality of life of affected patients. A common approach between oncologists, hepatologists and endoscopists would help improving the management and prognosis of the RE procedure and its complications.