Hepatic artery chemotherapy (HAC) was developed in the early 1960s to treat large, unresectable primary and secondary liver tumors 12. This approach is based on the rationale that local therapy through the hepatic artery increases the exposure of the liver tumors to cytotoxic agents, leading to higher response rates while limiting systemic side effects like myelosuppression, mucositis and diarrhea. Surgical or percutaneous placement of a subcutaneous device allows chemotherapy to be delivered continuously into the gastroduodenal artery via a catheter. Regional chemotherapy predominantly for the treatment of colorectal liver metastases was increasingly used in the late 1980s and 1990s because of the limited efficacy of available systemic treatment options 3456789. This approach was also evaluated in the treatment of unresectable primary liver tumors and as adjuvant treatment after metastasectomy 1011121314. However, the application of floxuridine-deoxy-ribose (FUDR), a prodrug of 5-fluorouracil (5-FU) with a high liver extraction fraction, into the hepatic artery can cause several complications. Biliary toxicity is the dose limiting side effect of HAC with FUDR, usually indicated by an increase of bilirubin and liver enzymes 15161718. Other infrequent complications are gastric and duodenal ulcerations, mainly due to misperfusion. Rarely thrombosis, nausea, vomiting and diarrhea occur 161920. Pocket infections, development of cholangitis and liver abscesses have also been reported 21.

A rare complication of HAC is the formation of pseudoaneurysms of the hepatic artery. In this article we describe two patients who developed aneurysmatic cavities of the hepatic artery after regional chemotherapy with FUDR and presented with hemorrhage.

Pseudoaneurysms of the hepatic artery due to placement of a catheter into the gastroduodenal artery and treatment with continuous regional chemotherapy are described infrequently in the literature 91322. They can remain clinically silent even after continuation of the treatment 23. A few case reports describe the development of hemorrhage after rupture of the pseudoaneurysm or fistulation to a bile duct or the intestine 242526. Pseudoaneurysms usually develop after percutaneous or surgical procedures as a result of dissection of the vessel. A penetrating trauma leads to a disruption of the media without blood seepage through the adventitia. The late development after multiple courses of intra-arterial chemotherapy, as described in our two patients, emphasises the role of HAC as a potential cause. Hepatic artery aneurysms account for 20% of all visceral aneurysms 27. The rate of rupture was reported to be as high as 65%, with a mortality rate of 20% 28. Symptoms of rupture include abdominal pain in case of retroperitoneal bleeding and hematemesis or melena, if the aneurysm is in contact with the biliary tract or the duodenal lumen. Early interventional therapy is necessary to control hemorrhage. The preferred approach is a hepatic angiography with subsequent coil embolization because pseudoaneurysms are usually located adjacent to the hilum of the liver, making surgery difficult 2930313233. Major risks of this procedure include arterial dissection, artery occlusion, thromboembolic phenomena and intraprocedural rupture of the aneurysm. Recently, promising results were reported with endovascular stent-graft placement, but long-term results are still lacking 3435. There are also reports of successful treatment with computed tomography guided percutaneous embolization and ultrasound guided percutaneous thrombin injection 3637.

Considering the development and widespread use of more effective systemic chemotherapy, the use of regional chemotherapy decreased in the last years. A recent meta-analysis showed that FUDR-based HAC alone does not improve response rates and outcome compared with 5-FU based combination chemotherapy 38. However, the role of regional chemotherapy with FUDR in primary liver tumors and in combination with efficient systemic chemotherapy in colorectal liver metastases has not been defined yet. HAC should be utilized only in high-volume centers with expertise in this field due to the high technical demands of this procedure, since the rate of complications is clearly related to the surgeon's experience 39. Clinicians should be aware of the possibly life threatening complications in patients treated with HAC. Because of the unpredictable course of pseudoaneurysms, early treatment with interventional radiological techniques should be considered. In the case of our two patients, angiography with coil embolization was necessary to control the critical condition.

Hepatic artery pseudoaneurysms may complicate regional chemotherapy with floxuridine. Prompt angiography with coil embolization is the preferred treatment to avoid life threatening hemorrhage in these patients.

Both patients gave written informed consent for publication of their data for scientific purposes.

The authors declare that they have no competing interests.

PS and BCP collected the data and wrote the article. TP provided the angiography pictures, contributed to the analysis and interpretation of the data and revised the manuscript. All authors read and approved the final manuscript.