HYPERVASCULAR TUMORS AND PRE-SURGICAL DEVASCULARIZATION || ARTERIOVENOUS MALFORMATIONS
CHRONIC PELVIC PAIN || ENDOLEAKS

:: Hypervascular Tumors and Pre-surgical Devascularization

In reality, the majority of the target tumors and organs are the same for both of these indications, with the patient's health and the physician's treatment approach being either non-surgical (inoperable hypervascular tumors) or surgical (pre-surgical devascularization). In these cases, embolization with a "bland" embolic, i.e. an embolic agent without adjunctive chemotherapy is indicated.

The target organs for the majority of the cases will be the kidney, liver, spleen, and sites resulting from metastases from tumors in these organs. In addition, tumors in the pancreas, lung and colon may be treatable with embolization.

Both embolization of inoperable hypervascular tumors and pre-surgical embolization of target organs usually involve organs with focal tumors. This is particularly true in vital singular organs, e.g. the liver and the pancreas. Other organs, such as the kidney (one of them) and the spleen may be removed entirely without significant consequences. The embolization of inoperable hypervascular tumors is often performed as a palliative to reduce pain when hope for recovery is low. More recently, however, hypervascular tumors are being treated with bland embolics and with chemoembolics to control the tumor growth and to extend the life of the patient. Pre-surgical embolization, on the other hand, is usually performed to rid the organ of the tumor. The organ may be removed entirely or partially following embolization, with the goal of embolization to reduce the amount of blood loss during the excision of the organ.

The embolization of renal cell carcinoma (RCC) has been shown to be very effective, either as a non-surgical option or prior to surgical excision. Onishi (8) reported on the treatment of 54 patients with unresectable RCC and distant metastasis at the time of diagnosis. Twenty-four patients underwent transcatheter arterial embolization (TAE) with ethanol and 30 patients did not get the embolic. The median survival of the two groups was 229 days for the group receiving TAE and 116 days without TAE. The 1- and 2- and 3-year survival rates in the TAE group were 29%, 15%, and 10% respectively. In those patients not undergoing TAE, the corresponding survival rates were 13%, 7%, and 3%, respectively. The adverse effects in patients undergoing TAE with ethanol included fever, back pain on the affected side, nausea and vomiting, but all of the patients recovered from these adverse effects. In another report, Kauffmann (9) used an occlusive gel (Ethibloc) to embolize patients with advanced cancer of the kidney. In all cases, very high volumes (14-40 mL) of the embolizing agent were necessary to achieve total occlusion of the entire arterial compartment.

Renal cell carcinoma has also been treated successfully with embolic agents prior to surgical excision of the kidney. Kalman (10) reviewed the available literature which consisted of 389 papers. In total, 3225 case histories met the inclusion criteria for the review. The overall conclusion was that complete pre-operative renal artery embolization facilitates the excision of renal vein invading tumors. The optimal delay between embolization and the operation was probably one day. The embolization material of choice is ethanol. Palliative embolization of inoperable tumors with serious hemorrhage seems to have been successful in most cases. The scientific basis for the implementation of renal artery embolization in renal cell carcinoma, however, appears to be weak and controlled trials need to be performed.

Saitoh (11) also conducted a retrospective study of the literature to evaluate the long-term results of TAE with absolute ethanol for patients with RCC. Twenty patients, including 15 patients with stage IVb tumors, underwent ethanol TAE, with 12 of them followed by nephrectomy. The cumulative survival rates after 1, 3, and 5 years were 71%, 54%, and 54% in the surgical group, and 54%, 33% and 22% in the non-surgical group

Zielinski et. al. (12) reported a series of 474 patients with renal cell carcinoma who had radical nephrectomy. The overall 5- and 10-year survival rates for 118 patients embolized before nephrectomy was 62% and 47%, respectively, as compared to 35% and 23%, respectively, for a matched group of 116 patients treated with surgery alone (p=0.001).

Embolization with agents that initiate the formation of thrombus to effect the embolization have also been known to initiate potential complications, such as pulmonary embolism. To prevent pulmonary embolization of necrotic tumor thrombosis after RCC embolization, Hirota et al. (13) place suprarenal inferior vena cava (IVC) filters in their patients.

Additional benefits, such as reduced blood loss during surgical resection have also been shown in the literature. Lonser et al. (14) published a technical note from the National Institute of Disorders and Stroke that concluded that introperative perfusion of tumors with ethanol produced immediate blanching and devascularization and enhanced visualization and resection. Christensen et al. (15) has also published on this same subject.

Renal cell carcinoma metastasized to the spine is a frequent occurrence. Roscoe et al. (16) reported on the treatment of eight patients. Pre-operative devascularized lesions resulted in less blood loss (940 cc) versus 1975cc on average for non-embolized patients. In another clinical paper, Sun and Lang (17) published the results of pre-operative devascularization of patients with bone metastasis from RCC. Patients had less blood loss (460 cc ) when pre-operative embolization was performed with PVA particles than non-embolized patients (750 cc) (p < 0.01). Survival ranged from 3 to 56 months. Chatziioannou et al. (18) evaluated the effectiveness of complete vs. incomplete embolization in reducing blood loss in surgical patients with bone metastasic RCC. They found that complete embolization resulted in less blood loss (535 +/- 390 mL) vs. 1,247 +/- 1,047 mL). Transfusions were also less in the treated patients (1.3 +/- 1 unit vs. 2.4 +/- 1.2 units). In addition to the benefits of reducing blood loss during surgery, embolization of metastatic RCC has also been reported to alleviate pain and the need for surgical decompression of the spine (Keuther, et al., 19).

The treatment of inoperable hepatocellular carcinoma (HCC) has been a frustrating experience, with most patients surviving only approximately 6 months after diagnosis. Although surgical resection is the only curative treatment, clinicians continue to search for options for the non-surgical patient. Although transcatheter chemoembolization (TACE) has been the mainstay for the past 15 years, the effectiveness of this local chemotherapy remains controversial for these patients. To date, the benefits of TACE have not been proven in a prospective randomized trial. In addition, there are several TACE treatment approaches, ranging from one-time treatment to repeated treatments every 6-8 weeks. Bland embolization or embolization without chemotherapy has been the choice of some groups, including Sloan-Kettering Hospital in New York (20).

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:: Arteriovenous Malformations (AVM)

An arteriovenous malformation (AVM) is a tangle of abnormally connected arteries and veins. Although the majority of these AVMs occur in the brain, AVMs also occur in the vasculature of the trunk and are usually referred to as AVMs of the upper extremity (UE) or of the lower extremity (LE).

Uterine AVMs are uncommon, but are potentially life-threatening lesions. In the past, most uterine AVMs have been managed surgically by hysterectomy with or without hypogastric artery ligation. Markoff et al. (21) has published on the successful bilateral embolization of the hypogastric arteries with a liquid polymer, isobutyl 2-cyanoacrylate (Bucrylate). Chow et al. (22) also reported the use of polyvinyl alcohol particles (Ivalon) and fragments of gelatin sponge as being effective in the treatment of uterine AVMs.

In 2000, White et al. (23) reported on a series of 20 patients that were treated with embolotherapy in combination with surgery for the management of symptomatic high-flow AVMs of the lower and upper extremities. Nine patients presented with pain and skin ulceration (n=7) associated with LE-AVMs. All 11 UE-AVM patients had debilitating pain. Seven had weakness of the affected hand and two had bony erosion. Embolization of the nidus beneath the site of maximum pain or ulceration was performed percutaneously from the femoral artery through coaxially placed microcatheters (n=18) or surgical cutdown (n=2). Cyanoacrylate (isobutyl or n-butyl) diluted with iophendylate or ethiodized oil was used in 19 of 20 patients. Long -term follow of these patients revealed that embolotherapy alone or in combination with surgical resection of the AVM provided excellent palliation in patients with UE-AVM. The LE-AVM patients were also followed up (mean 8.6 years). Five of the nine LE-AVM patients had subsequent leg amputations 1-6 years after successful embolization. In three of these patients, the trifurcation arteries were diffusely involved in the AVM.

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:: Chronic Pelvic Pain

Chronic pelvic pain (CPP), defined as noncyclic abdominal and pelvic pain of at least 6 months duration, may account for approximately 10% of outpatient gynecologic visits and for one-third of diagnostic laparoscopies performed (24). The contributing causes include the following: endometriosis, pelvic adhesions, atypical menstrual pain, urologic disorders, irritable bowel syndrome, and psychosocial issues. In 1984, a series that correlated laparoscopic and venographic findings in women with unexplained CPP showed that up to 91% of the women had marked pelvic venous congestion (25). Pelvic congestion syndrome (PCS), a condition associated with ovarian vein (OV) incompetence, is manifested by pelvic pain of variable intensity that is heightened before or during menses and that is aggravated by prolonged standing, fatigue, and coitus. The traditional therapy involves medical management and / or surgery.

Cordts et al. (26) reported on a series of 11 women who were referred to the vascular clinic for the evaluation of the following: lower extremity varicosities (n=6), vulvar varicies (n=2), tubo-ovarian varicosities diagnosed either by laparoscopy or ultrasound for chronic pain (n=3). Nine of the women underwent embolization with either 0.035 inch Gianturco stainless steel coils or 0.018 inch platinum microcoils. An average of 16 coils was used for each ovarian vein that was embolized (range 6-24 coils). No liquid sclerosants were used. Parallel ovarian vein trunks that entered the main trunk or that directly entered the left renal vein were embolized as well. The mean follow-up was 13.4 months. Although 8 of the 9 embolized patients experienced excellent initial pain relief (>80%), two patients complained of symptom return from 6-22 months post procedure. One of these two patients was lost to follow-up. The other patient underwent another venography that revealed the both ovarian veins were thrombosed. The left common iliac vein was patent however, and there was significant cross filling of the pelvic collaterals from left to right via the hypogastric veins. No further treatment was performed.

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:: Endoleaks Associated with AAA Stent Grafts

Complications associated with abdominal aortic aneurysms (AAA) is the 13th leading cause of death in the United States. The treatment of AAA with endovascular stent grafts has become a safe therapy that is effective over the short-term (27). The major problem is the occurrence of endoleaks, which occur early after the operation in 66% of the patients and late in 20-30% of the patients (28). Many endoleaks seal spontaneously by thrombus formation during the follow-up period. Other endoleaks are persistent and require intervention or the aneurysm sac will continue to be under pressure and will eventually rupture.

Although the approaches to ensure long-term success of endovascular stent graft repair remain controversial, several authors have embraced the concept of embolization of endoleaks to assist in the shrinkage of the aneurysmal sac. Ermis et al. (29) reported on the use of coils to treat the endoleaks in 15 AAA stent graft patients. In 8 patients, coil embolization failed to completely obliterate the leak, whereas, embolotherapy proved successful in the remaining 7 patients. Surveillance of the endoleaks and the effect of their embolization on aneurysm size were followed with serial CT scans for at least 12 months. Successfully treated patients showed a mean decrease from 20.58 +/- 3.63 (median 19.87) to 16.36 +/- 6.46 cm2, whereas the patients with an unsuccessful endoleak treatment exhibited a slight increase in mean aneurysm area from 21.41 +/- 4.25 to 22.47 +/- 6.70 cm2.

Recently, Fry et al. (30) commented in an editorial that there may be a need for a paradigm shift in the approach to the treatment of type II endoleaks. The authors reported on the use of a liquid embolic agent (Onyx, MicroTherapeutics, Inc.) injected into the sac of the aneurysm through a translumbar approach. The authors suggest that the use of a liquid embolic agent may be more effective than coils since the recanalization of blood flow within the interstices of coils and coil compaction also potentially limit the effectiveness and durability of coil repair of type II endoleaks. The results of their research were recently reported in a series of six patients with a follow-up of 7-29 weeks (mean = 19.2 weeks) after treatment (31). In these patients, translumbar access to the aneurysm sac was attempted in four patients. Direct endoleak access was attained in three of four patients using a catheter that was guided through the translumbar sheath. Onyx was slowly injected while the delivery catheter was gradually withdrawn, forming a cast of the endoleak sac. Aneurysm sacs decreased in size in all cases (range, 1.5-3 mm: average 1.8mm, p < 0.002). A small endoleak persisted in one patient in whom endoleak access was not successful. All patients remained asymptomatic 20-37 weeks after treatment.

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