Chemical Ablation of Liver Lesions

Chapter 144


Chemical Ablation of Liver Lesions


Joshua L. Weintraub, Thomas J. Ward and John H. Rundback


The presentation of a patient with a liver lesion ranges from the patient with an incidentally discovered and asymptomatic simple liver cyst to the patient with multifocal primary or metastatic liver tumors. The interventions used to treat this wide range of lesions is equally as varied, with percutaneous chemical ablation having a continually evolving role.



Chemical Ablation of Benign Liver Lesions


Simple Liver Cysts


Liver cysts are common, with a prevalence of approximately 2.5% in the general population and a female predominance.1 A majority of these cysts are incidentally discovered by ultrasound or computed tomography (CT) and are clinically insignificant, so no further evaluation or treatment is necessary. For a minority of patients, larger cysts can produce symptoms that range from abdominal discomfort and nausea to compression of the biliary tree or inferior vena cava, intraperitoneal rupture, hemorrhage, torsion, or infection.26 The majority of symptomatic cysts occur in females older than 50, with a 9 : 1 female-to-male ratio and a predisposition for the right hepatic lobe.7


Previous attempts at percutaneous treatment of the symptomatic cyst focused on cyst aspiration. This strategy produced suboptimal results due to high rates of cyst recurrence, with reported recurrence rates between 78% and 100%.8,9 Advances in percutaneous treatment of liver cysts occurred with the introduction of ablative agents that treat the underlying pathology of the process. True simple hepatic cysts have an epithelial lining and are the result of congenitally aberrant bile ducts that are separated from the remainder of the intrahepatic biliary tract. The columnar or cuboidal epithelial cells that line the cyst produce fluid that reaccumulates after simple aspiration.


With newer techniques, after cyst aspiration a variety of chemical agents (e.g., tetracycline hydrochloride, doxycycline, minocycline hydrochloride, hypertonic saline) have been injected into the cyst in an attempt to decrease previously observed recurrence rates by damaging the fluid-producing cells.1013 The most studied chemical agent administered for this purpose is ethanol, which produces epithelial cell damage that prevents fluid secretion and results in subsequent cyst destruction.



Percutaneous Ethanol Sclerotherapy


Indications


Percutaneous ethanol sclerotherapy (PES) is indicated in the setting of a hepatic cyst that produces clinically significant mass effect on adjacent structures, such as biliary obstruction or compression of the inferior vena cava, abdominal pain, or other significant symptomatology that affects the patient’s quality of life (Fig. e144-1). In the setting of abdominal pain, care must be taken to exclude other etiologies for the patient’s symptoms before proceeding with intervention, since approximately 85% of cysts are asymptomatic.2,14 Furthermore, the lesion to be treated must be definitively identified as a simple cyst and not a cystadenoma, cystadenocarcinoma, or other malignancy. In the setting of an indeterminate lesion or hemorrhage into a simple cyst, definitive identification with magnetic resonance imaging (MRI) can generally be obtained. If there is uncertainty that a discovered cyst is the cause of the patient’s pain, a trial of simple aspiration can be performed, with ethanol sclerosis performed in the setting of symptomatic cyst recurrence.







Technique


PES is performed with real-time ultrasound guidance, at which time the location, depth, and angle for the puncture site is determined. The procedure itself has not significantly changed since Bean and Rodan’s paper in the American Journal of Radiology 25 years ago.17 The procedure is performed with mild sedation and sterile technique, with prophylactic antibiotics generally not administered. Local 1% lidocaine is administered at the determined puncture site prior to gaining access to the cyst via an 18-gauge needle. Access to and characterization of the cyst is confirmed with fluid aspiration. The first 20 mL of fluid is sent for laboratory evaluation to exclude malignancy or infection. A 0.035-inch Amplatz wire is placed through the needle into the cyst, with the needle then withdrawn. The Seldinger technique is used to advance a 6F to 12F multipurpose drainage catheter with side holes into the cyst after appropriate fascial dilatation. All fluid is then aspirated from the cyst, with complete drainage confirmed via ultrasound examination. The evacuated cyst cavity is then injected with dilute water-soluble contrast and fluoroscopy, or a CT scan is performed to evaluate for a communication between the cyst and the biliary tree or peritoneal cavity.


The contrast material is then removed prior to instillation of sterile ethanol. The volume of ethanol instilled is generally selected to be between 25% and 40% of the volume of cyst fluid aspirated. The drainage catheter is then capped, and the ethanol is left in place for 20 to 30 minutes, with the patient rolled into various positions to ensure treatment of all surfaces of the cyst cavity. The ethanol is then aspirated, with the volume removed generally found to be greater than the volume injected because of the release of loculated pockets of fluid or dead cells. This procedure may be repeated in the setting of large cysts (generally > 400 mL). The catheter is then removed and the skin bandaged. A study that compared single-session ethanol sclerotherapy to prolonged catheter drainage with negative pressure demonstrated similar results between the two methods, with statistically insignificant differences in regard to average cyst volume reduction, final cyst volume, or cyst disappearance rates.18


Should the patient experience significant pain, the ethanol is immediately aspirated off, generally with subsequent resolution of the patient’s acute symptomatology. Lidocaine may be injected into the cyst cavity via the drainage catheter prior to ethanol administration to minimize the occurrence of this event.



Controversies


The principle controversies surrounding hepatic cyst PES focus on the appropriateness of the treatment and whether laparoscopic treatment is more appropriate as first-line treatment. There is little debate that hepatic cysts that produce significant mass effect on adjacent structures should be treated. Treatment performed for abdominal discomfort or pain is more controversial. Care must be taken to exclude other etiologies for the patient’s symptoms prior to intervention. Performing interventionalists may prefer to do a trial cyst aspiration without sclerotherapy. If symptoms do not abate, the cyst in question is excluded as the cause of pain. Should pain resolve after aspiration and recur with cyst recurrence, PES may be advised.


A variety of options are available for surgical management. Prior to widespread use of laparoscopic surgeries, open cystectomy, hepatic wedge resections, and lobectomies were performed, with significant rates of morbidity and mortality. In comparison, laparoscopic “de-roofing” has significantly lowered adverse events, cost, and length of stay, with low rates of recurrence.1921 No prospective randomized control studies have been performed that compare percutaneous to laparoscopic treatment. As such, the expertise of the physicians at the performing institution generally guides treatment decisions.



Outcomes


PES is effective at reducing cyst volume and relieving the symptoms for which the procedure is performed. A review of the literature performed by Drenth et al. of 34 articles that involved 292 patients with solitary or multiple hepatic cysts demonstrated an at-least-partial recurrence rate of 21% during follow-up, with the majority being asymptomatic and reintervention rarely performed.22 The largest study examined cyst size reduction and symptom relief in 25 patients with 59 symptomatic hepatic cysts, with 11 patients having a single cyst. Overall, 8 cysts resolved completely, and mean diameter of remaining cysts decreased from 9 to 3 cm. Symptoms completely resolved or improved in all patients with solitary cysts; symptoms recurred in 7 patients with polycystic liver disease, owing to growth of other untreated cysts.23




Postprocedural and Follow-up Care


If tolerated without immediate complication, PES can be performed as an outpatient procedure. Short-term follow-up at 1 to 2 months with ultrasound is generally performed, with further follow-up performed only for symptom recurrence. A small sample of 39 benign intraabdominal cysts, 21 hepatic, that were treated with PES followed by frequent ultrasound during the first year demonstrated that of those cysts that recurred, all recurred at a smaller volume and subsequently decreased spontaneously in size without intervention. The authors concluded that initial recurrence after percutaneous ablation is usually a transient reactive inflammatory reaction and not true treatment failure.24 Should symptoms recur in the setting of cyst recurrence, repeat PES or laparoscopic de-roofing may be considered.



Puncture, Aspiration, Injection, and Reaspiration of Cystic Echinococcosis


Cystic echinococcosis (CE) is a zoonotic infection of the Echinococcus tapeworm, with Echinococcus granulosus and Echinococcus multilocularis being the species that most commonly cause human disease. In endemic areas and Middle Eastern, South American, and Mediterranean countries, the annual incidence of CE ranges from 1 to 200 per 100,000, with a mortality rate of 2% to 4% and higher mortality rates seen in the setting of inadequate medical care.25 CE can affect multiple organ systems, although 80% of patients present with a solitary cyst, most commonly hepatic.26 Disease presentation and progression is markedly variable. Cysts may remain stable for years, regress or resolve spontaneously, or grow rapidly with symptom onset generally secondary to mass effect on adjacent structures, although intraperitoneal rupture and subsequent anaphylaxis can occur.


Traditionally, surgical management has been the standard of care for treating active or symptomatic CE because of the fear that percutaneous treatment could result in spillage of cyst contents and peritoneal seeding or a fatal anaphylactic reaction. Use of the anthelmintic chemotherapy drugs mebendazole and albendazole prior to percutaneous intervention decreases this risk and has resulted in increased use of percutaneous treatment strategies at many high-volume centers (Fig. e144-2).27





Indications


The appropriateness for a puncture, aspiration, injection, and reaspiration (PAIR) treatment strategy depends on the complexity and activity of the cyst being treated. In 1996, the World Health Organization Informal Working Group on Echinococcosis (WHO-IWGE) produced a standardized classification system to replace the previous classification schemes.28 The most popular scheme at the time was proposed by Gharbi et al. in 1981 and is still regularly referenced.29


PAIR is first-line treatment for WHO-IWGE CE1 and CE3a cysts (Gharbi types 1 and 2).30 These cysts contain clear fluid; a detached membrane and daughter cysts may or may not be present. It is also indicated for patients who are not surgical candidates, patients who refuse surgery, and for cases that failed surgery or medical management.





Technique


PAIR of CE is performed with real-time ultrasound or CT guidance after the diagnosis of CE is confirmed with an indirect hemagglutination test (IHA), or enzyme-linked immunosorbent assay (ELISA) confirms the presence of antibodies against Echinococcosis, and ultrasound or CT has identified a characteristic cyst. Albendazole or mebendazole is administered at least 4 hours before the procedure and continued for 1 month after.31


The procedure is performed with conscious sedation as well as continuous cardiac and hemodynamic monitoring, with resuscitation equipment close at hand. Prophylactic antibiotics are generally not administered. Local 1% lidocaine is administered at the determined puncture site prior to gaining access to the cyst via an 18- to 22-gauge needle. When possible, an intercostal approach is taken, with the puncture trajectory selected to traverse at least 1 cm of normal liver to prevent spillage of cyst contents. Access to and characterization of the cyst is confirmed with fluid aspiration. Cyst fluid is then aspirated, with fluid sent for parasitologic evaluation.


Evaluation for biliary communication can be performed with fluoroscopy or CT after injection of dilute water-soluble contrast or by testing the aspirated fluid for bilirubin. After biliary communication is excluded, a scolicidal agent—sterile 20% hypertonic saline or 95% ethanol—is injected. The volume administered is approximately 50% of the volume of cystic fluid aspirated. The agent is left in place for 20 minutes and the patient rolled in different positions to ensure uniform mixing of the cyst contents with the hypertonic saline or ethanol. The fluid is then completely removed.


In the case of large cysts (>10 cm in diameter), a PAIR procedure may be performed with drainage (PAIR-D). Following a traditional PAIR procedure, a 0.035-inch Amplatz wire is placed through the needle into the cyst, with the needle then withdrawn. The Seldinger technique is used to advance an 8F multipurpose drainage catheter with side holes into the cyst, with care taken to only dilate the tract through the subcutaneous tissues and most superficial liver to reduce the risk of cyst content spillage. The drainage catheter is left to drainage and irrigated with isotonic fluid 4 or 5 times daily until drain output is less than 10 mL/day.32



Controversies


Controversy initially surrounded the safety of percutaneous treatment of CE with PAIR, owing to the fear that this strategy would result in increased rates of peritoneal seeding or anaphylactic reactions. For decades, CE was treated with an open surgical approach, but after the introduction of chemotherapeutic drugs to treat CE, there has been increased interest in percutaneous management. Large series have since demonstrated PAIR to be a safe and efficacious treatment strategy that is supported by long-term data when appropriate patient selection criteria are used.30,33


The optimal protoscolicidal agent is also a point of controversy. No study has demonstrated superiority of ethanol over hypertonic saline, although some believe ethanol is more sclerosing and results in quicker cyst involution.33,34 In the setting of cystobiliary communication, however, the risk of sclerosing cholangitis precludes administering ethanol.



Outcomes


Smego et al. performed a large meta-analysis of 769 patients with CE who were treated with PAIR and albendazole or mebendazole, compared to 952 era-matched historical control subjects treated surgically. PAIR produced clinical and parasitologic cure in 95.8% of patients, compared to 89.8% in the surgical group (P < .0001).27 Rates of cyst disappearance or solidification observed with follow-up ultrasound after PAIR generally range from 80% to 100%.30,32,35 Postprocedure seroconversion rates, as determined by serial IHAs or ELISAs, range from 50% to 100% in smaller studies.30,34,36,37 A statistically significant lower rate of disease recurrence was also observed with PAIR compared to surgery: 1.6% to 6.3%, resectively.27




Dec 23, 2015 | Posted by in INTERVENTIONAL RADIOLOGY | Comments Off on Chemical Ablation of Liver Lesions

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