Catheter-based transarterial therapies for hepatocellular cancer
ABSTRACTAs the prevalence of liver cancer increases, so does the demand for nonsurgical, minimally invasive alternatives to surgery, since many patients have tumors that cannot be surgically resected. Catheter-based hepatic arterial procedures may be an option in patients with primary and metastatic liver cancer. The authors describe four catheter-based hepatic arterial procedures and outline the management of potential complications during the immediate postprocedural period.
KEY POINTS
- Bland embolization carries a risk of pulmonary embolism if there is shunting between the pulmonary and hepatic circulation via the hepatic vein. Technetium-99m macro-aggregated albumin scanning is done before the procedure to assess the risk.
- Postembolization syndrome—characterized by low-grade fever, mild leukocytosis, and pain—is common after chemoembolization. Therefore, after the procedure, the patient is admitted to the hospital overnight for monitoring and control of symptoms such as pain and nausea.
- Puncture-site complications include hematoma, pseudo-aneurysm, infection, nerve damage, and arterial thrombosis. Systemic complications include postembolization syndrome, tumor lysis syndrome, hypersensitivity reactions, and contrast-induced nephropathy.
PUNCTURE-SITE COMPLICATIONS
Hematoma
Hematoma at the puncture site is the most common complication of arterial access, with an incidence of 5% to 23%. The main clinical findings are erythema and swelling at the puncture site, with a palpable hardening of the skin. Pain and decreased range of motion in the affected extremity can also occur.
Simple hematomas exhibit a stable size and hemoglobin count and are managed conservatively. Initial management involves marking the site and checking frequently for a change in size, as well as applying pressure. Strict bed rest is recommended, with the affected leg kept straight for 4 to 6 hours. The hemoglobin concentration and hematocrit should be monitored for acute blood loss. Simple hematomas usually resolve in 2 to 4 weeks.
Complicated hematoma is characterized by continuous blood loss and can be compounded by a coagulopathy coexistent with underlying liver disease. Severe blood loss can result in hypotension and tachycardia with an acute drop in the hemoglobin concentration.
Of note, a complicated hematoma can manifest superficially in the groin and may not change size over time, as most of the bleeding is intrapelvic.
Complicated hematomas require management by an interventional radiologist, including urgent noncontrast CT of the pelvis to evaluate for bleeding. In severe cases, embolization or stent graft placement by the interventional radiologist may be necessary. Open surgical evacuation is usually done only when compartment syndrome is a concern.24–26
Pseudoaneurysm
Pseudoaneurysm occurs in 0.5% to 9% of patients who undergo arterial puncture. It primarily arises from difficulty with cannulation of the artery and from inadequate compression after removal of the vascular sheath.
The signs of pseudoaneurysm are similar to those of hematoma, but it presents with a palpable thrill or bruit on auscultation. Ultrasonography is used for diagnosis.
As with hematoma treatment, bed rest and close monitoring are important. Mild pseudoaneurysm usually responds to manual compression for 20 to 30 minutes. More severe cases may require surgical intervention or percutaneous thrombin injection under ultrasonographic guidance.25,27
Infection
Infection of the puncture site is rare, with an incidence of about 1%. However, with the advent of closure devices such as Angio-Seal (St. Jude Medical), the incidence of infection has been on the rise, as these devices leave a tract from the skin to the vessel, providing a nidus for infection.25,28
The hallmarks of infection are straightforward and include pain, swelling, erythema, fever, and leukocytosis, and treatment involves antibiotics.
Nerve damage
In rare cases, puncture or postprocedural compression can damage surrounding nerves. The incidence of nerve damage is less than 0.5%. Symptoms include numbness and tingling at the access site and limb weakness. Treatment involves symptomatic management and physical therapy. Nerve damage can also result from nerve sheath compression by a hematoma.25,29
Arterial thrombosis
Arterial thrombosis can occur at the site of sheath entry, but this can be avoided by administering anticoagulation during the procedure. Classic symptoms include the “5 P’s”: pain, pallor, paresthesia, pulselessness, and paralysis. Treatment depends on the clot burden, with small clots potentially dissolving and larger clots requiring possible thrombolysis, embolectomy, or surgery.25,30
SYSTEMIC CONSIDERATIONS
Postembolization syndrome
Postembolization syndrome is characterized by low-grade fever, mild leukocytosis, and pain. Although not a true complication of the procedure, it is an expected event in postprocedural care and should not be confused with systemic infection.
The pathophysiology of postembolization syndrome is not completely understood, but it is believed to be a sequela of liver necrosis and resulting inflammatory reaction.31 The incidence has been reported to be as high as 90% to 95%, with 81% of patients reporting nausea, vomiting, malaise, and myalgias; 42% of patients experience low-grade fever.32 Higher doses of chemotherapy and inadvertent embolization of the gallbladder have been associated with a higher incidence of postembolization syndrome.32
Symptoms typically peak within 5 days of the procedure and can last up to 10 days. If symptoms do not resolve during this time, infection should be ruled out. Blood cultures and aspirates from infarcted liver tissue remain sterile in postembolization syndrome, thus helping to rule out infection.32
Treatment with corticosteroids, analgesics, antinausea drugs, and intravenous fluids have all been used individually or in combination, with varying success rates. Prophylactic antibiotic treatment does not appear to play a role.33
Tumor lysis syndrome
Tumor lysis syndrome—a complex of severe metabolic disturbances potentially resulting in nephropathy and kidney failure—is extremely rare, with only a handful of individual case reports. It can occur with any embolization technique. Hsieh et al34 reported two cases arising 24 hours to 3 days after treatment. Hsieh et al,34 Burney,35 and Sakamoto et al36 reported tumor lysis syndrome in patients with tumors larger than 5 cm, suggesting that these patients may be at higher risk.
Tumor lysis syndrome typically presents with oliguria and subsequently progresses to electrolyte abnormalities, defined by Cairo and Bishop37 as a 25% increase or decrease in the serum concentration of two of the following within 7 days after tumor therapy: uric acid, potassium, calcium, or phosphate. Treatment involves correction of electrolyte disturbances, as well as aggressive rehydration and allopurinol for high uric acid levels.
Hypersensitivity to iodinated contrast
Contrast reactions range from immediate (within 1 hour) to delayed (from 1 hour to several days after administration). The most common symptoms of an immediate reaction are pruritus, flushing, angioedema, bronchospasm, wheezing, hypotension, and shock. Delayed reactions typically involve mild to moderate skin rash, mild angioedema, minor erythema multiforme, and, rarely, Stevens-Johnson syndrome.38 Dermatology consultation should always be considered for delayed reactions, particularly for severe skin manifestations.
Immediate reactions should be treated with intravenous (IV) fluid support and bronchodilators, and in life-threatening situations, epinephrine. Treatment of delayed reaction is guided by the symptoms. If the reaction is mild (pruritus or rash), secure IV access, have oxygen on standby, begin IV fluids, and consider giving diphenhydramine 50 mg IV or by mouth. Hydrocortisone 200 mg IV can be substituted if the patient has a diphen-hydramine allergy. For severe reactions, epinephrine (1:1,000 intramuscularly or 1:10,000 IV) should be given immediately.39
Ideally, high-risk patients (ie, those with known contrast allergies) should avoid contrast medium if possible. However, if contrast is necessary, premedication should be provided. The American College of Radiology recommends the following preprocedural regimen: prednisone 50 mg by mouth 13 hours, 7 hours, and 1 hour before contrast administration, then 50 mg of diphenhydramine (IV, intramuscular, or oral) 1 hour before the procedure. Methylprednisolone 32 mg by mouth 12 hours and 2 hours before the procedure is an alternative to prednisone; 200 mg of IV hydrocortisone can be used if the patient cannot take oral medication.40–42
Hypersensitivity to embolizing agents
In chemoembolization procedures, ethiodized oil is used as both a contrast medium and an occluding agent. This lipiodol suspension is combined and injected with the chemotherapy drug. Hypersensitivity reactions have been reported, but the mechanism is not well understood.
One study43 showed a 3.2% occurrence of hypersensitivity to lipiodol combined with cisplatin, a frequently used combination. The most common reaction was dyspnea and urticaria (observed in 57% of patients); bronchospasm, altered mental status, and pruritus were also observed in lower frequencies. Treatment involved corticosteroids and antihistamines; blood pressure support with vasopressors was used as needed.43
Contrast-induced nephropathy
Contrast-induced nephropathy is defined as a 25% rise in serum creatinine from baseline after exposure to iodinated contrast agents. Patients particularly at risk include those with preexisting renal impairment, diabetes mellitus, or acute renal failure due to dehydration. Other risk factors include age, preexisting cardiovascular disease, and hepatic impairment.
Prophylactic strategies rely primarily on intravenous hydration before exposure. The use of N-acetylcysteine can also be considered, but its effectiveness is controversial and it is not routinely recommended in the United States.
Managing acute renal failure, whether new or due to chronic renal impairment, should first involve rehydration. In cases of a severe rise in creatinine or uremia, dialysis should be considered as well as a nephrology consultation.44,45
