Acute hemorrhage can be a life-threatening complication in cancer patients and is a significant cause of morbidity and mortality1-³⁾. It occurs in approximately 6-10% of cancer patients3, ⁴⁾. Medical treatment for acute hemorrhage includes compression, drug therapy, blood transfusion, hydration and other supportive care. Other therapeutic strategies include radiotherapy, surgical therapy, such as vessel ligation or the resection of hemorrhagic tissue³⁾. However, the inherent morbidity of the surgical procedures in debilitated patients, and the efficacy of medical treatment may make this approach problematic3, ⁵⁾. Therefore, selective arterial embolization (SAE) is increasingly preferred as a therapeutic procedure for controlling hemorrhage, normally in adults. Furthermore, SAE is applied increasingly in conditions, such as hemorrhage, arterio-venous malformation, arteriovenous fistula, aneurysm and tumors6-⁹⁾. However, SAE is performed less frequently in pediatric patients. This may be secondary to the stress of the procedure itself, lack of doctor`s experience and possible long-term side effects⁸⁾. Therefore, the aim of this retrospective study was to determine the efficacy and safety of SAE in the treatment of intractable hemorrhage in pediatric patients with malignancies.

From January 2004 to December 2009, the medical records of 6 pediatric patients with a malignancy who underwent SAE of the internal iliac artery at Chonnam National University Hwasun Hospital were analyzed retrospectively. All patients presented with intractable hemorrhage, which had not responded to earlier conservative measures. Data on the following items were documented: general characteristics, underlying disease, treatment of underlying disease, number of SAE performed, response to SAE, side effects related to the procedure and follow-up duration. The complications related to the SAE procedure, including nausea, vomiting, fever, development of hematoma, infection, vascular perforation, ischemia, and pain were also examined. SAE was performed by an interventional radiologist under fluoroscopic guidance after patients had been appropriately sedated. The Gelfoam® (Pfizer Inc., New York, NY, USA) and/or Tornado® coils (Cook Inc., Bloomington, IN, USA) were used as embolic agents.

In cases of hemorrhagic cystitis (HC), the onset time and duration of HC before SAE were reviewed. HC was graded according to the criteria previously reported⁹⁾: grade 1, continuation of microscopic hematuria for more than 2 days; grade 2, gross hematuria; grade 3, gross hematuria with a clot; grade 4, gross hematuria with renal impairment due to urinary tract obstruction with a clot.

In cancer patients, acute hemorrhage is a well-known complication that is associated with high morbidity and mortality3, ⁵⁾. Various therapeutic approaches have been attempted including intensive supportive care with compression, hydration, blood transfusion, drug therapy and surgical care3, 5, ⁹⁾. However, there is no specific and effective treatment. Some patients do not respond to medical care5, ¹¹⁾. Surgical treatment is the ultimate therapeutic approach for controlling refractory hemorrhage but is associated with high morbidity and mortality because of the poor general condition of the cancer patients or underlying disease as well as the complications arising from treatment of the underlying disease2, ¹²⁾. SAE is a minimally invasive procedure with a lower rate of morbidity, having obvious advantages over surgery. Therefore, it is an accepted approach and is used more often to treat intractable hemorrhage5, 12, ¹³⁾.

The SAE of the internal iliac artery was first reported in 1973 as a mean to control the bleeding associated with pelvic fractures¹⁶⁾. In 1974, Halad and Myging¹⁷⁾ were the first to describe the use of SAE of the internal iliac artery to control HC secondary to radiation therapy for bladder cancer. Since then, the indications for SAE of the internal iliac artery to control intractable hemorrhage have widened¹⁸⁾, including the management of hemorrhage resulting from trauma, iatrogenic or obstetrical causes, and pelvic or urological neoplasm2, 5, 9, 14, 15, ¹⁹⁾. In this study, all 6 children had an acute pelvic cavity hemorrhage resulting from HC, iatrogenic vascular injuries or rupture of a retroperitoneal tumor, which could not be controlled by medical treatment. SAE of the internal iliac artery was attempted as surgical therapy was impossible due to the poor general condition of the patients and their low platelet counts. The bleeding was brought under control in 5 of the 6 patients (83.3%) after SAE. The remaining one patient died of uncontrollable bleeding despite the SAE procedure because of poor general condition associated with underlying hypotensive shock. These results are similar to those of previous studies showing the efficacy of SAE2, 5, 9, 11, 12, 14, ¹⁵⁾.

According to Han et al.⁵⁾, 10 patients with grade 3-4 HC following allogeneic HSCT underwent SAE of the internal iliac artery. The unsuccessful medical treatments performed before SAE included the following: hyperhydration, blood transfusion, intravesical instillation of granulocyte, monocyte-colony stimulating factor, bladder irrigation, and antiviral agents. Eight patients responded to SAE within 15 days. Surgical treatment, such as cauterization with cystoscopy or cystectomy, was not necessary⁵⁾. There were several reports about successful SAE; 2 adults with HC who received an allogeneic HSCT²⁾ and 6 patients (mean age 80 years) with bladder or prostate carcinoma, who all patients were embolized successfully within 8 days and without complications¹²⁾. SAE was also performed successfully in instances of severe postpartum hemorrhage, pelvic fracture or trauma15, ²⁰⁾.

During the follow-up period, 2 children underwent a second SAE due to a relapse of the hemorrhage but there were no recurrences after the second procedure. This finding is comparable to that of other studies. In the recent study, 6 adult patients were reported who underwent selective embolization of the bladder arteries for treatment of incoercible hematuria. All patients with hematuria responded within 48 hours after the procedure, but two patients had a recurrence of the bleeding that required a second procedure²¹⁾. In 2007 report, among 7 patients with intractable bladder hemorrhage who underwent internal iliac artery embolization, but bleeding was controlled permanently in 4 (57%) patients and a second embolization was required in 1 patient²²⁾. In the other study of 44 patients with an advanced pelvic tumor (mean age 79 years; range 51-95), the initial embolization produced complete control of the bleeding in 36 of the 44 patients (82%). However, subsequent arterial embolization was required in 5 patients (11%) and was successful²³⁾. In addition, this procedure can also be used to diagnose and treat aneurysms, arterio-venous malformation or tumors6, 24, ²⁵⁾.

However, SAE is performed less frequently in children, particularly in pediatric cancer patients6-8, ²⁴⁾. A search of the literature on SAE in the pediatric population revealed only a few reports. Legge et al.⁸⁾ performed SAE in 5 pediatric patients suffering from hypersplenism, hemobilia, sigmoid hemangioma and aneurysmal bone cysts in the iliac bone. Embolization provided definitive treatment in all cases without complications. Bilateral internal pudendal artery embolization was performed for intractable priapism in a 14-year-old boy with chronic myelogenous leukemia⁷⁾. A month-old baby with a mycotic internal iliac aneurysm underwent successful coil embolization⁶⁾. Erkan²⁴⁾ also carried out SAE for the treatment of pelvic aneurysmal bone cysts in two children. Along with the reported cases, our data on 6 patients support the effectiveness of SAE for the treatment of refractory hemorrhage in children with a malignancy.

A range of materials have been used for embolization including muscle, autologous clots, gelatin, coil, and balloon²⁶⁾. Gelfoam® and/or coil were used for embolization. Gelfoam®, a gelatin sponge, is a water-insoluble hemostatic material that is easy to handle. It is biodegradable or absorbable, and the vessel recanalizes within a few weeks. Consequently, it has fewer complications of vascular occlusion than using coil or surgical vessel ligation8, ²⁶⁾. A coil is effective either for fast flowing vessels or when needed to occlude a vessel permanently²³⁾.

The complications associated with SAE include nausea, vomiting, fever, infection, pain, hematoma, vascular perforation, chills, claudication, erectile dysfunction, urinary retention, and paresthesia5, 12, 17, 26-²⁸⁾. However, serious side effects are rare26, ²⁹⁾ and can be reduced by precise placement of the coil or Gelfoam® to preserve tissue perfusion12, 21, ³⁰⁾. In the current study, there were no side effects encountered during the follow-up period, but it will be necessary to carefully observe these patients for possible long-term complications, such as claudication, sexual dysfunction and paresthesia26-²⁸⁾.

In conclusion, bleeding was controlled in 5 out of 6 children (83.3%) after SAE of the internal iliac artery without side effects. The results suggest that SAE of the internal iliac artery is an effective and safe therapeutic approach in pediatric cancer patients with hemorrhage who do not respond to supportive care. SAE can also reduce the patients` exposure to the risks inherent with the surgical procedures. Further clinical trials involving a larger number of patients will be needed to evaluate the potential role, safety and possible long-term side effects of SAE in children with malignancies.