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Biopsy, Needle Localization, and RadiofrequencyAblation for Pediatric Patients

Fredric A. Hoffer, MD FAAP, FSIR

Pediatric interventions for oncology patients include aspiration orpercutaneous biopsy for malignancy diagnosis or recurrence,and percutaneous biopsy for the complications of tumor treat-ment. Tumor localization techniques have been used to resectsmall lesions with minimal invasion. However improved guidancetechniques have allowed for more precise biopsy and the use ofthermal ablation instead of excision for local tumor control. I willdiscuss these diagnostic and therapeutic techniques as theyapply to children. 2003 Elsevier Inc. All rights reserved.

Atraumatic CareAtraumatic care is important when dealing with pediatric on-cology patients. When children face a chronic disease, anypainful experience will sour their outlook and heighten thereaversion to pain. It is important to place topical anestheticpreparations such as lidocaine/prilocaine or 4% lidocaine onthe skin for 60 to 45 minutes, respectively, with an occlusivedressing before obtaining percutaneous or IV access. Prilocainecannot be used in the newborn due to the risk of methemoglo-binemia. I prefer to have an anesthesiologist in attendance forall biopsies and ablations.

Percutaneous Tumor Biopsy

As a pediatric radiologist I perform more biopsies than anysingle surgeon in our institution. This reliance on percutaneousbiopsy occurs in many adult hospitals but is not as widespreadin pediatric institutions. Building a successful biopsy practiceinvolves carefully planning how the material is obtained andprocessed. Adult carcinomas often can be diagnosed by cytol-ogy alone. Pediatric tumors, which are often lymphoma, sar-coma, and blastoma, often appear as small round blue cells andneed core biopsy tissue for further analysis. Obtaining corebiopsies with a 15-G spring-loaded core biopsy needle helps thepathologist have adequate tissue for histopathology, immuno-pathology, molecular pathology, and cytogenetics. Immuno-

histochemical staining can be obtained from specimens pre-served in 10% formalin.

Obtaining genetic information is often necessary to differen-tiate these small blue round-cell tumors. Genetic testing re-quires at least two passes with a 15-G needle and the placementof the fresh material in RPMI 1640 (Roswell Park MedicalCenter) transport media. In the past, I relied on culturing thetumor for cytogenetic analysis.1,2 At St. Jude and other majoroncology centers, a solid tumor panel of genetic translocations(t) can be screened with a polymerase chain reaction (PCR)technique (in the department of molecular pathology). Thesolid tumor PCR panel includes at least Ewing sarcoma family

of tumors [t(11;22)(21;22)], alveolar rhabdomyosarcoma [t(2;13)], and synovial sarcoma [t(X;18)].

Fresh tissue placed in RPMI 1640 is also used for FISH(fluorescent in situ hybridization) techniques. The FISH tech-nique obtains the genetic information necessary to establishprognosis for neuroblastoma including MYCN gene amplifica-tion and loss of the short arm of the first chromosome (1p),which are poor prognostic indicators. FISH for 1p can also beobtained in Wilms tumor to assign risk-based treatment. TheDNA index (ploidy) of the primary tumor is also necessary forthe treatment of neuroblastoma and can be obtained from twopasses of a 15-G core biopsy needle.3 Low DNA index (diploid)of the primary neuroblastoma in the first 2 years of life corre-

lates with a poor prognosis.The Childrens Oncology Group, the one remaining cooper-ative cancer group for children in the United States, also re-quires a determination of favorable or unfavorable histology forneuroblastoma based on the Shimada pathology classificationsystem.4 This requires examining the excised specimen grosslyto determine tissue nodularity and microscopically to count1000 cells. I have shown that imaging and percutaneous needlesampling of the primary tumor is sufficient to assign favorableor unfavorable histology for neuroblastoma.3 Unfortunately,percutaneous biopsy material is not currently accepted for in-clusion in a COG neuroblastoma protocol.

Recently, I have studied percutaneous biopsy and aspirationmaterial obtained for the diagnosis and recurrence of lym-

phoma and leukemia.5 Percutaneous biopsy of lymphoma in-cluding Hodgkins disease is usually diagnostic. Drainage oraspiration of a fluid collection associated with non-Hodgkinslymphoma or leukemia is often diagnostic and is less invasivethan biopsy. To diagnose Hodgkins disease, one has to be luckyenough to find a Reed Sternberg cell. The other hematologicmalignancies need to be identified by histology and immuno-chemistry. Formalin-fixed tissue can be stained for antibodies,a technique termed immunohistochemical staining. Flow cy-tometry can analyze antibody labeling of the tumor from freshtissue placed in RPMI 1640. If an aspirate of a fluid collection issubmitted for flow cytometry, it should be heparinized. Some

From the Division of Diagnostic Imaging, Department of RadiologicalSciences, St. Jude Childrens Research Hospital, Memphis, Tennessee,USA.

Supported in part by Cancer Center Support (CORE) Grant CA 21765from the National Cancer Institute and by the American Lebanese SyrianAssociated Charities (ALSAC).

Address reprint requests to Fredric A. Hoffer, MD, Division of Diagnos-tic Imaging, Department of Radiological Sciences, St. Jude ChildrensResearch Hospital, 332 N. Lauderdale St., Memphis, TN 38105, USA.Fax: 901-495-4398. E-mail: fred.hoffer@stjude.org

2003 Elsevier Inc. All rights reserved.1089-2516/03/0604-0007$30.00/0doi:10.1053/j.tvir.2003.10.003

Techniques in Vascular and Interventional Radiology, Vol 6, No 4 (December), 2003: pp 192-196192

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children with large mediastinal masses could obstruct theirairway or systemic venous return during anesthesia. If theyhave impaired peak expiratory flow or tracheal narrowing over50%,6 the least sedation possible should be used for a simplepercutaneous needle aspiration or more invasive percutaneousbiopsy.

Lung Biopsy for Invasive Aspergillosis

Invasive pulmonary aspergillosis occurs with frightening regu-larity in our immunosuppressed patients.7 A mortality rate of82% has been reported for recipients of bone marrow trans-plants.8 Until now, none of our patients have survived withoutsurgical resection. The newer antifungal agents show promiseof controlling this disease without resection. Galactomannan, acell-wall antigen of Aspergillus, can now be detected in theperipheral circulation. Using this test and the enhanced CTappearance may be all that is necessary to diagnose this infec-tion. The halo around a small nodule is an early imaging char-acteristic of invasive aspergillosis. Central necrosis on en-hanced CT or MR is a reliable sign ina larger nodule in a patientwith an absolute neutrophil count (ANC) of less than 1000cells/ mm3. When the ANC is in the normal 1000 range, a

crescent of air may appear between the necrotic center andviable rim of the pulmonary aspergillosis. Percutaneous CT-guided biopsy of the lesion is fairly accurate7 and will selectpatients that would benefit from pulmonary resection. Whenbiopsying the lung, I often use a coaxial technique with a 19-Gsheath and a 20-Gspring-loaded core biopsy needle. Material issent for KOH preparation, fungal cultures, and histopathology.

Liver Biopsy Techniques: Transjugular orCoaxial Percutaneous

I have performed percutaneous coaxial hepatic biopsies andtransjugular hepatic biopsies on pediatric oncology patients.9

Percutaneous liver biopsies are reserved for patients that do nothave an increased risk of bleeding. Transjugular liver biopsy isindicated for patients with coagulopathy, thrombocytopenia,prolonged bleeding time, ascites, or those at risk of hepaticvenous hypertension: bone marrow or stem cell transplant re-cipients at risk of hepatic venoocclusive disease (HVOD) fromday7 to day 30.

Percutaneous technique is always guided by color-flowDoppler sonography (US) to avoid vessels. One gram of micro-fibrillar collagen (Avitene, MedChem Products, Inc. Woburn,MA) is mixed with 10 mL of normal saline and drawn up into a1-mL syringe. A 17-G sheath and 18 spring-loaded biopsy nee-dle is used for the coaxial biopsy. The collagen mixture is theninjected into the 17-G sheath under US guidance as the sheath

is withdrawn. Color-flow Doppler US can then monitor bleed-ing from the tract. Bleeding will have color flow and the colla-gen will appear echogenic without flow. To document thequantity of hemosiderosis in patients who have undergonechronic transfusions, two dry specimens should be sent in ametal-free container surrounded by ice.

The transjugular technique starts with free-hand US guid-ance to access the internal jugular vein. Then a LABS 200system (Cook, Inc., Bloomington, IN) is used with a spring-loaded 19-G core biopsy needle through the hepatic vein. Bi-opsy is rarely required to document HVOD disease since it isusually diagnosed clinically with a triad of weight gain, jaun-

dice, and hepatic tenderness or enlargement. If a transjugularbiopsy is done, measurement of the free and wedge hepaticvenous pressures may document the portal hypertension thatoccurs with this disease. Many are performed after day 21when engraftment of the transplanted cells occurs and the pa-tient becomes more jaundiced with suspected graft versus hostdisease. In this setting, I obtain material for histopathology,viral, bacterial, and fungal culture, and most recently PCR forspecific viruses.

Tumor Localization

I have used a Kopans breast biopsy needle (Cook, Inc.) todeliver 0.1to 0.2mL of methylene blue dye and a hooked wire10

into small masses for excisional biopsy. However, I prefer tobiopsy smalllesions, recurrences, or metastases under real-timeCT or US guidance and then ablate them with radiofrequencyrather than have them excised by surgery. Needle localizationhas been most useful when a small lung nodule is present underthe pleural surface. This will not be seen and cannot be feltduring thoracoscopic surgery. Needle localization has allowedless invasive thoracoscopic surgery to replace conventionalthoracotomy for excision of these lesions.

Guidance Techniques

If a lesion can be visualized by US, this is the preferred guidancemodality for any percutaneous procedure. The disadvantage ofusing US with radiofrequency (RF) ablation is that the gas thatforms during the ablation may obscure the far edge of thetumor. European radiologists have the advantage of readilyaccessible ultrasound contrast agents.11 US contrast agentsmake lesions more conspicuous, which allows more preciseplacement of the RF probe into the mass. More importantly,when the RF ablation is thought to be completed, additional UScontrast agent can be given. If a portion of the tumor remains

viable, the RF probe can be repositioned and the remainingtissue can be ablated before the session ends.

Pulmonary and osseous lesions are best approached with CTguidance. Real-time CT (CT fluoroscopy) may generate exces-sive radiation dosage to the examiner and the child unless usedin a spot-check manner.12 A compromise CT guidance systemis a single- or multislice-image acquisition controlled by theradiologist in the CT scanning room. Although not a real-timetechnique, the radiologist can get spot CT images within sec-onds of needle or probe manipulation and view them withoutleaving the room. If there is a small lung nodule, the youngpatient may require general anesthesia with controlled breath-ing during biopsy or RF probe advancement. Virtual CT guid-ance systems (e.g., UltraGuide, Inc., Lakewood, CO and Tirat

Hicarmel, Israel) are also available and may aid in biopsy or RFablation of small liver nodules that are not visible on either USor noncontrast CT. This technique allows the real-time projec-tion of a needle or probe onto the preexisting contrast-en-hanced CT image. This technique also allows off-axial guidanceof the needle placement. Combined CT and US guidance maybe necessary for some difficult biopsies or ablations.

Radiofrequency Ablation of Osteoid Osteoma

Osteoid osteoma is a common benign cortical bone lesion inchildren and adults that classically gives the patient night pain

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partially relieved by anti-inflammatory agents. The radiolucentnidus isnot usually larger than 1 cm indiameter and is best seenon CT. The nidus produces a sclerotic reaction in the corticalbone as noted by radiograph or CT and inflammation in themedullary portion of the bone as noted by MR or scintigraphy.RF ablation is the treatment method of choice for osteoid os-teoma in children and adults.13 Rosenthal recently reportedexperience in over 250 patients with primary and secondarysuccess rates of 91 and 60%, respectively, with immediate relief

of pain.13

Surgical excision of the osteoid osteoma is unneces-sary and carries the risk of missing the lesion and fracturing thebone.14 Percutaneous excision under CT guidance is an alter-native.15 The percutaneous excision requires a large trephineneedle driven by an electric drill. The nidus and a considerableportion of cortex are excised. Because of the cortical bone lossand the risk of fracture, the patients are kept on crutches for 6weeks after the core excision.

The technique for RF ablation of osteoid osteoma is welldeveloped.16,17 The patient is placed under general anesthesiasince the biopsy or ablation of an osteoid osteoma is very pain-ful. The lesion can be biopsied with a 14-G Ackerman needleunder CT guidance. This allows passage of a 17-G RF probeinto the center of thenidus. I recommendusinga thermocouple

(TC) noncooled probe with a 5-mm active tip (Radionics, Di-vision of Tyco Health care group LP, Burlington, MA). Thisprobe distributes heat over a 1-cm-diameter volume, effectivelyablating the small nidus of the osteoid osteoma.13 The sheathmust be pulled back so that it is over 1 cm from the activeportion of the RF probe. This will avoid heating the sheath andthe soft tissue, nerves, and skin the sheath passes through ornear. The generator is placed on manual mode and tempera-tures of 90C are obtained for 4 to 6 minutes. If a portion of thenidus is not within 5 mm of the probe tip, the probe is reposi-tioned and the ablation repeated. The patient can then be re-covered and sent home. If the pain persists or recurs, a repeatablation can be performed.

One could safely perform the osteoid osteoma RF ablationtechnique with the Cool-Tip system (Radionics) with a 1-cmactive tip probe but with the cooling turned off. Cooling the tipof the RF probe will burn a larger area (3 cm in diameter orlarger) than necessary and increase the risk of a delayed patho-logic fracture. Because this Radionics system is so precise, anosteoid osteoma in the vertebral body neighboring the spinalcanal has been safely treated with a noncooled RF probe with-out spinal cord injury.18 Nondeployed multiprong or umbrella-shaped probes should be avoided when treating osteoid os-teoma at any location. The prongs cannot be fully deployed inthe small nidus. The generated heat is distributed down theshaft of the probe and may damage neighboring nerves or skin.Other manufacturers are now developing straight single-tip

probes for RF tumor ablation but usually coupled with infusionports that distribute saline in to the surrounding tissues andextend the diameter of the burn. Saline infusion should not beused in conjunction with RF ablation for the osteoid osteoma.

Radiofrequency Tumor Ablation in thePediatric Patient

I have gained experience performing RF ablation of pediatrictumors including in an open phase I protocol for RF ablation ofmalignant tumors (usually metastases) in the liver, lung, andmusculoskeletal system acquired during childhood. Some tu-

mors such as hepatoblastoma and osteosarcoma are not sensi-tive to radiotherapy and benefit from complete excision. Ifsurgical excision of these tumors or their metastases is notpossible, RF ablation is warranted.

A pain service consultation is obtained before the procedure;all pediatric patients are placed under general anesthesia, andpatient-controlled analgesia is arranged as an inpatient at leastovernight after the tumor ablation. I prefer to use the RadionicsCool Tip ablation system and have found that using the triple-

cluster probe is most effective. Cooling of the tip and imped-ance control allows larger burn areas by avoiding high temper-atures and charring near the probe. Burn times of 12 minutesper position are required in the liver and shorter burn times areallowed in less vascular organs such as the lung or musculo-skeletal system. If temperatures of 60C are obtained, theninstantaneous tissue death is assured. Temperatures over 50Cover several minutes will also completely ablate the tumor.Overlapping burns should be performed so that all the tumorand cuff of 1 cm normal tissue (which may harbor microscopicdisease) reach these critical temperatures. When the ablationcycle in each position is finished, the cooling is turned off andthe probe is heated to 80C without impedance control to as-sure that the tissue in contact with the probe is also ablated.

This noncooling technique can also be performed as the needleis withdrawn at 1-minute intervals to burn the needle tract andprevent tumor spread and bleeding. The probe can be touchedto assure there is no burning of the skin as it is withdrawn.

The Italian investigators have the most experience using RFfor ablating hepatomas or hepatic metastases describing 0.3%mortality and 2.2% major complication rate for liver tumor RFablation19 in adults. RFA is now applied successfully to tumorsup to 7 cm in diameter. Even larger hepatic tumors have beenablated with RF.20 I have had the opportunity to RF ablatepediatric liver metastases from colon cancer, rhabdomyosar-coma, pancreatoblastoma, and hepatocellular carcinoma. ThisRFA technique has been taken to the extreme when treating

carcinoid syndrome.21

Multiple hepatic lesions can be ablatedat one time and remaining lesions can be treated at later ses-sions, allowing regeneration of the liver between ablations. Thevolume of ablation is only limited by the risk of renal insuffi-ciency from tumor lysis, myoglobinuria, and hemoglobin-uria22-24. The renal insufficiency may be avoided by aggressivehydration duringand after RF ablation. Other manifestations oftumor lysis syndrome include fever, nausea, pain, and fatigue.23

Other complications of RFA include damage to neighboringbile ducts or bowel. These thin-walled systems may be burnedand leak their contents. Patients who have had a prior biliaryenteric anastomosis are at a high risk of developing a hepaticabscess. They shouldunderstand the risks of RF ablation andbetreated with prophylactic antibiotics.

RFA of primary or metastatic lung cancer has been success-fully performed in adults25-28. Surgical excision of osteosar-coma metastases to the lung does improve outcome.29 Surgeryoften finds multiple small lesions undetected by CT. However,there may be diminishing returns for performing repeat thora-cotomy for recurrent pulmonary metastases. Exposure of theentire pleural surface will become more difficult and thoraco-scopic excision after pleural adhesions may be impossible.There is a 91% recurrence rate of pulmonary osteosarcomametastases after initial thoracotomy30; 45% of the nodules recurat the surgical scar. RFA of recurrent lesions may be warrantedafter the initial thoracotomy.

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RFA of lung nodules can be performed with either cooled tipprobes or umbrella probes. Stroke from air embolus into thepulmonary veins is a potentialrisk when performing RFA of thelung. Although there has been only one report of a stroke,27 onestudy found small air emboli passing through the carotid arteryduring lung RFA without any clinical sequelae.28 I have ablatedpulmonary metastases in one patient with synovial sarcomausing a triple-cluster Cool-Tip Radionics RF probe.

Children do on occasion develop painful bone metastases.

The pain of bone metastases in adults has been successfullyrelieved by RFA.31,32 Even spinal metastases have been targetedwith RFA. The lesion is approached from the long axis of thebone if possible. If the cortex is intact, a core biopsy can be

performed with a 14-G Trephine needle. This hole will allow asingle-cooled tip RF probe to be placed inthe bone. If the cortexis thinned or disrupted, then a triple-cooled tip probe or anumbrella RF device can be placed. Lesions with diameters of 5to 10 cm can be effectively ablated with these probes. Weight-bearing lesions have also been treated with RFA when com-bined with cementoplasty,32 which I would recommend if morethan one-third of the weight-bearing cortex is burned duringthe RF ablation. RF-ablated tissue shrinks just like cookedmeat. This allows space for the cement to be placed.

RF ablation may have a future role in controlling aggressivefibromatosis (desmoid tumors). These lesions are locally ag-gressive and recur after surgical resection. Radiotherapy andchemotherapy33 have had limited success. There has been one

report of using acetic acid to ablate desmoid tumors not ame-nable to surgical resection.34 The technique was staged so thatthe inner portion of the tumor was first ablated. The tumor thenshrank away from vital structures, allowing for complete abla-tion. RF ablation could accomplish the same task. If there is acontiguous vital nerve, the portion of the desmoid tumor that isdistant from the nerve could first be ablated. This may allow thedesmoid tumor to fall away from the nerve.

RF ablation can damage central or peripheral nerves if tem-

perature of the nerves exceeds 45C. Because of this, osseousRFA has been performed in adult patients under conscioussedation so that nerve stimulation can be detected. This wouldbe impossible in pediatric patients. Other means of monitoringnerve function in children under general anesthesia would be

necessary. One can monitor the temperature near a major nerveor spinal canal using a percutaneously placed temperatureprobe. One can avoid using paralytics during anesthesia todetect motor nerve stimulation. When contemplating RF abla-tion of malignant tumors in the spine, one should choose le-sions that are at least 1 cm away from the spinal canal to protectthe spinal cord.

RFA has been performed in adults with renal cell carci-

noma.35,36

Peripheral renal lesions are more likely to be com-pletely ablated without complications. The pediatric equivalentwould be perilobar nephroblastomatosis and bilateral Wilmstumor. Initially, nephron-sparing surgery would be most effi-cacious. However, persistent or recurrent masses may be diffi-cult to treat with surgical re-excision. RFA could potentiallytreat the peripheral masses in the unresected kidney.

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