Chemical and Thermal Ablation of Desmoid Tumors



Chemical and Thermal Ablation of Desmoid Tumors


David S. Pryluck, Joseph P. Erinjeri and Timothy W.I. Clark


Desmoid tumors, or aggressive fibromatosis, are low-grade sarcomas composed of highly differentiated monoclonal fibroblasts with extensive collagen overgrowth. The incidence of sporadic desmoid tumors in the general population is estimated at two to five persons per million per year. Desmoids occur in 16% to 20% of patients with familial adenomatous polyposis (FAP) syndromes such as Gardner syndrome and produce significant morbidity. Desmoids are the second most common cause of death in patients with FAP, after colon cancer. Along with FAP, risk factors for desmoid tumors include surgical trauma, female gender, parity, bone malformations, and connective tissue disorders. Genetic risk has been associated with a mutation in the APC-β-catenin-Tcf pathway in both sporadic and FAP-associated desmoid tumors. Stabilization of β-catenin-Tcf in transgenic murine models has been shown to produce desmoids in 75% of unwounded animals after 3 months and excessive fibroblast proliferation in 100% of mice with cutaneous wounds after only 24 days.


Desmoid tumors are locally infiltrative, and although they rarely metastasize, extensive morbidity and even mortality can occur from compression of adjacent organs. Growth of desmoids is characterized by extension along fascial planes with invasion of neurovascular structures (Fig. 162-1, A). Primary surgical treatment consists of wide excision or limb amputation. Recurrence develops in 25% to 70% of cases despite tumor-free margins, often within several months after resection. In approximately 90% of patients with positive margins, disease rapidly recurs within several months after resection.



Therapy for desmoid tumors is extremely challenging and limited by the wide spectrum of the condition. The majority of the published literature is confined to single case reports, with a paucity of prospective studies.


Percutaneous image-guided techniques including chemical ablation, cryoablation, and radiofrequency ablation (RFA) are now being utilized as part of an interdisciplinary approach to treating desmoid tumors. These techniques, which have routinely been used in the treatment of hepatic, renal, and osseous neoplasms, may be uniquely suited for many of the challenges encountered in the treatment of desmoid tumors, and can be used as a primary treatment modality, an adjunct to chemotherapy or radiation, or as salvage therapy following postsurgical recurrence. The underlying goal should be improvement of pain and function in each patient. This chapter will discuss the mechanism of action, technical and clinical considerations, and a brief review of the existing medical literature for each technique as applied to the treatment of desmoid tumors.



Chemical Ablation


Percutaneous chemical ablation with 50% acetic acid or absolute ethanol has been used for in situ destruction of desmoid tumors (Fig. 162-2, B). The cytotoxic effects of acetic acid are derived from protein desiccation, lipid dissolution, and collagen extraction, whereas those of ethanol are attributed to cytoplasmic dehydration, denaturation of cellular proteins, and small vessel thrombosis. These effects culminate in coagulative necrosis indistinguishable from thermal ablation techniques. Instances of significant tumor reduction have been observed after even a single session of chemical ablation, suggesting that other mechanisms such as apoptosis or immune-modulated tumor destruction may also play a role in tumor regression.






Equipment


Devices needed for percutaneous chemical ablation of desmoid tumors are readily available in most interventional radiology practices and include:






Technique


Anatomy and Approach


Chemical ablation of desmoid tumors involves targeting the center of the tumor through a percutaneous window that does not traverse collateral structures. Desmoid tumors may be oblong or irregular in shape and require insertion of more than one needle during the treatment session. Acetic acid is prepared in the hospital pharmacy by combining 10 mL of glacial acetic acid (U.S. Pharmacopeia) with 10 mL of sterile water. The resultant solution of 50% acetic acid is filtered through a Millex-GV 0.22-µm filter (Millipore, Bedford, MA) to ensure sterility. This solution is then delivered to the interventional radiology department in a stoppered sterile glass bottle. Patients must be informed that acetic acid is not approved for injection by the U.S. Food and Drug Administration (FDA), although it is used in various medical applications, including as a buffering agent for dialysate solutions and for diagnostic purposes during colposcopy to detect and characterize cervical lesions.


Infusion needles are positioned in the desmoid tumor under local anesthesia. Patients also receive conscious sedation (intravenous midazolam and fentanyl citrate) during the procedure for local pain during the injection. With ultrasound, the needles are positioned within the central core of the tumor before injection of the chemical agent.


After positioning of one to three needles within the center of the desmoid tumor, acetic acid is infused. Real-time ultrasound monitoring is preferable. It is vital that an extremely slow rate of infusion be used. For this reason, a calibrated 1-mL Luer-Lok syringe is helpful. This enables the operator to accurately monitor the rate and pressure of injection. Generally, acetic acid is injected at a rate of approximately 0.1 mL per 15 to 20 seconds. A rapid burst of the agent is undesirable; rather, the technique relies on steady and gradual dispersal of the agent. As acetic acid penetrates through the tumor, the baseline hypoechoic echotexture of the tumor will become immediately hyperechoic (see Fig. 162-2). Further injection is performed as the needle is slowly withdrawn away from the central core of the tumor in an attempt to render the inner aspect of the tumor as uniformly echogenic as possible. The volume of acetic acid during an individual treatment session is divided between the additional infusion needles. In total, no more than 10 mL of acetic acid is injected in a single treatment session. Even large tumors may require a much smaller volume than this to produce a large area of echogenicity in the tumor. Because desmoids are not encapsulated, great care must be taken to not allow extravasation of the agent through the interstices of the tumor. Care is also taken to ensure distribution of acetic acid in the peripheral margins. If the periphery of the tumor becomes hyperechoic during the injection, the infusion is stopped, and the needle is either repositioned or withdrawn.


All patients are given a dose of broad-spectrum parenteral antibiotic at the time of the procedure. Patients are discharged home after a period of 4 hours of observation and then seen back in the interventional radiology clinic the day after the procedure to assess overlying skin integrity and evaluate for local changes of tumor inflammation.


It is important to use a staged approach to therapy. Treatment sessions are spaced 4 to 5 weeks apart.



Technical Aspects




• Real-time ultrasound monitoring during chemical ablation is preferable.


• A single intravenous dose of a broad-spectrum antibiotic (e.g., cefazolin, vancomycin) is given.


• Conscious sedation is achieved with intravenous fentanyl citrate and midazolam.


• One to three needles (Bernardino, Chiba) are positioned within the center of the desmoid tumor under local anesthesia.


• Once the needles are positioned, acetic acid is injected through a single needle at a rate of approximately 0.1 mL per 15 to 20 seconds via a calibrated 1-mL Luer-Lok syringe.


• The desmoid tumor will change from a hypoechoic appearance to a bright echotexture during injection.


• The injection is performed to a sonographic endpoint to render the central two thirds of the tumor as uniformly echogenic as possible.


• Further injection is performed as the needle is slowly withdrawn away from the central core of the tumor in an attempt to render the inner aspect of the tumor as uniformly echogenic as possible.


• The needle is removed after aspiration to minimize seepage of acetic acid during tumor withdrawal.


• The same process is repeated with the remaining needle or needles.


• In total, no more than 10 mL of 50% acetic acid is injected during a single treatment session.


• When needles are reinserted during subsequent treatment sessions, brownish sterile fluid from necrotic tumor tissue as a result of previous treatment may be encountered. This fluid is aspirated before injection of additional acetic acid.



Outcomes


After our initial description of one partial response and a sustained complete response in two patients, we have performed approximately 60 additional treatment sessions of percutaneous chemical ablation in 20 cumulative patients. Our unpublished observations, including logistic regression of CT and MRI volumetric analysis of tumor regression patterns after chemical ablation, have shown that 60% of patients have a mean decrease in tumor volume of 30%. A subset of these patients will experience more dramatic responses, including those with complete resolution of enhancing tumor tissue on follow-up MRI. Parallel to a reduction in tumor size, these patients also experience improvement in function and a decrease in pain, many of whom required daily oral or transdermal narcotic analgesics (or both) before ablation. Moreover, these patients will no longer have central enhancement of their tumor on T1-weighted gadolinium-enhanced MRI. However, we currently limit treatment to patients with desmoid tumors that are 10 cm or less in maximum diameter and those who have a tumor located in an area that is percutaneously accessible without evidence of encasement of a major neurovascular structure or vital organ.


Dec 23, 2015 | Posted by in INTERVENTIONAL RADIOLOGY | Comments Off on Chemical and Thermal Ablation of Desmoid Tumors
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