AJR 2004; 183:209-213
© American Roentgen Ray Society
Histopathologic Evaluation of Tissue Extracted on the Radiofrequency Probe After Ablation of Liver Tumors: Preliminary Findings
Constantinos T. Sofocleous1,2,
Kenneth M. Klein3,
Basil Hubbi4,
Karen T. Brown2,
Stanley H. Weiss5,
George Kannarkat4,
Clay R. Hinrichs1,
Daniel Contractor1,
Philip Bahramipour1,
Allison Barone1 and
Stephen R. Baker1
1 Department of Radiology, University of Medicine and Dentistry of New
Jersey–Newark, Newark, NJ.
2 Present address: Department of Interventional Radiology, Memorial
Sloan-Kettering Cancer Center, Weil Medical College, Cornell University, 1275
York Ave., New York, NY 10021.
3 Department of Pathology, University of Medicine and Dentistry of New
Jersey–Newark, Newark, NJ.
4 New Jersey Medical School, University of Medicine and Dentistry of New
Jersey–Newark, Newark, NJ.
5 Department of Epidemiology and Preventive Medicine, New Jersey Medical School,
University of Medicine and Dentistry of New Jersey–Newark, Newark,
NJ.
Received August 28, 2003;
accepted after revision January 21, 2004.
Address correspondence to C. T. Sofocleous
(constant{at}pol.net).
Abstract
OBJECTIVE. Our aim was to evaluate the histologic characteristics of
tissue extracted on the probe immediately after radiofrequency ablation of
malignant tumors in the liver.
MATERIALS AND METHODS. From April to December 2001, 20
radiofrequency ablations were performed in 19 patients with primary
(n = 17) and metastatic (n = 2) liver masses. Track ablation
according to device protocol was performed after each ablation. Tissue was
adherent to the probe after all radiofrequency probe passes. All pieces of
tissue found on the probe were collected and preserved in formalin.
RESULTS. Tissue was examined by the study pathologist. In eight
(40%) of 20 specimens, coagulation necrosis was present. In five (25%) of 20
specimens, possibly nonviable tissue was extracted, although some cell
characteristics were identified. In seven (35%) of 20 specimens with
hepatocellular carcinoma, possibly viable tissue was found. Five specimens
were identified as hepatocellular carcinoma, and two, as cirrhotic
nodules.
CONCLUSION. Histopathologic evaluation of the tissue extracted on
the radiofrequency probe after ablation is feasible. This study showed that
coagulation necrosis was clearly present in at least 40% of the patients,
which proves that nonviable tissue can be seen immediately after ablation.
Whether this pathologic finding has prognostic value is not known.
Introduction
Tumor ablation with thermal energy sources, such as radiofrequency, laser,
or microwave, is receiving increasing attention as treatment for focal
malignant liver tumors
[1–5].
These methods permit local tumor destruction with minimal damage to
surrounding tissue and are being used to treat focal hepatic malignancy.
Percutaneous, imaging-guided, radiofrequency ablation of tumors is used in
patients who are not considered candidates for anatomic surgical hepatic
resection because of age, comorbidity, or extent of disease. Radiofrequency
ablation has also been reported to reduce the size of, or stabilize, hepatic
tumors in patients awaiting liver transplantation
[6,
7].
Although complications of radiofrequency ablation are rare
[2], limitations of thermal
energy therapy include tumor seeding along the ablation track
[8], incomplete tumor ablation
[6,] and posttreatment
recurrence [7,
9].
While performing a series of percutaneous radiofrequency ablations of liver
tumors, we noticed that tissue always adhered to the probe and its electrodes
after each use, and we postulated that histologic assessment of the viability
of this tissue might be feasible and could conceivably be used in the future
as a predictor of treatment outcome. This preliminary report describes the
histopathologic characteristics of tissue extracted from the radiofrequency
probe after 20 ablations in 19 patients and shows that when the Radiofrequency
Interstitial Tumor Ablation (RITA) system (RITA Medical Systems) is used,
there is always adequate amount of tissue on the probe and its nine electrodes
to allow histologic examination and provide information regarding tissue
damage.
Materials and Methods
The study was designed to examine the histopathologic characteristics of
tissue extracted from the probe after radiofrequency ablation of liver tumors.
Institutional review board approval was obtained, and all patients signed
informed consent forms before the procedure. This series included patients who
underwent percutaneous radiofrequency ablation with the RITA system, using CT
guidance. The procedures were performed with the patients under general
anesthesia or IV sedation at the discretion of the consulting attending
anesthesiologist while the patient was under continuous electrophysiologic
monitoring. Each ablation was performed by one of four fellowship-trained
attending interventional radiologists with similar experience in the
performance of imaging-guided percutaneous radiofrequency ablation. From April
to December 2001, tissue was collected from 20 radiofrequency ablation
sessions performed in 19 patients with primary (n = 17) and
metastatic (n = 2) liver masses. Population demographics, preablation
tumor size and location, and pathologic findings are presented in
Table 1.
A detailed description of the radiofrequency ablation system that we used
has been made in a prior publication that reported application of laparoscopic
radiofrequency ablation [10].
In short, the radiofrequency generator (model 1500, RITA Medical Systems) was
activated to the power needed (maximum, 150 W) to achieve a probe temperature
(average thermocouple temperature, 105°C) resulting in cell death. The
target temperature monitored by the thermocouple is maintained for 5–14
min depending on the desired radius of necrosis (3–5 cm). In two lesions
larger than 5 cm in diameter, two overlapping areas of 5-cm ablations were
performed at the same session. After each ablation, a cooldown cycle was
performed by the automatic turnoff of the generator power. Mean temperature of
70°C at 60 sec after ablation indicates that a technically successful
ablation has been performed
[10]. Track ablation according
to device protocol (preservation of mean temperature at 
70°C) is
performed after the termination of the ablation and cooldown cycles
[10,
11], while the probe is
gradually withdrawn from the liver.
We observed that macroscopically identifiable tissue was always adherent to
the probe and its nine electrodes (tines or prongs) after each use (Fig.
1A,
1B). The entire amount of
tissue was collected from the needle of the thermal ablation probe and all its
reexpanded nine electrodes after the completion of percutaneous radiofrequency
ablation. All the fragments of tissue found on the probe and the electrodes
after each radiofrequency ablation session were collected. The specimens,
measuring 5–11 mm in length (Fig.
1B), were collected by the interventional radiologist, placed in
formalin, and sent to the laboratory for examination by the study pathologist.
The specimens were handled like any surgical specimen: They were fixed in 10%
formalin, dehydrated and embedded in paraffin, and then cut into 5-µm-thick
sections. They were subsequently stained with H and E and Masson trichrome to
define fibrosis.
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Fig. 1A. —Tissue fragments extracted by radiofrequency ablation probe.
Photograph shows needle probe after radiofrequency ablation and removal from
patient's body, with fragments of extracted tissue on reexpanded
electrodes.
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The pathologic findings were classified as one of the following:
coagulation necrosis (nonviable tissue), findings of coagulation necrosis
without identifiable cell characteristics
(Fig. 2A); possibly nonviable
tissues, tumor cells that are smudged and somewhat distorted, with poorly
identified cytoplasm and nuclei identified between areas of coagulation
necrosis (Fig. 2B); and
possibly viable tissues, cell characteristics of malignant cells
(hepatocellular carcinoma) or cirrhotic nodules or both
(Fig. 2C).
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Fig. 2B. —Histopathologic findings after radiofrequency ablation.
Photomicrograph shows possibly nonviable tissue. Coagulation necrosis is
interrupted by nest of tumor (hepatocellular carcinoma) cells, which are
smudged and somewhat distorted. Cytoplasm and nuclei of tumor cells are not as
clearly seen (Table 1, patient
14).
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Results
All tissue fragments were collected and examined by the study pathologist.
In eight (40%) of 20 specimens, coagulation necrosis (nonviable tissue) was
present (Table 1 and
Fig. 2A) without any
preservation of cellular characteristics. In five (25%) of 20 specimens,
possibly nonviable tissue was classified, although some cell characteristics
were identified (Table 1 and
Fig. 2B). In these specimens,
areas of coagulation necrosis were interrupted by the presence of cells that
preserved their cell membrane, protoplasm, and nuclei and were therefore
identifiable. In seven (35%) of 20 specimens, possibly viable tissue was
found: five cases with hepatocellular carcinoma and two with cirrhotic nodules
(Table 1). In five of these
specimens, several nests of cells with characteristics of malignancy
consistent with hepatocellular carcinoma were present
(Fig. 2C). In the other two, no
evidence of malignancy was found, but cellular characteristics diagnostic of
cirrhosis were present. Changes of coagulation necrosis, although present,
were inconsistent and much less evident in specimens classified as possibly
viable.
Discussion
Imaging-guided radiofrequency ablation is a promising technique for the
treatment of unresectable hepatic tumors
[4,
5], with a relatively low
incidence of complications [2,
12] and shortcomings such as
incomplete tumor ablation [6],
tumor developing in a new location
[7], local tumor recurrence or
progression [9], and tumor
seeding of the percutaneous ablation track
[8].
In a prior study, radiofrequency ablation of liver tumors using internally
cooled electrodes (Radionics) was followed by surgical excision and subsequent
pathologic examination that showed no coagulation necrosis immediately after
treatment. In specimens removed and examined 3 days or later, definite
contiguous coagulation necrosis without intervening areas of viable tumor was
seen [13]. Our specimens
extracted by the RITA probe and evaluated immediately after treatment showed
coagulation necrosis in a significant number (40%) of specimens. This finding
alone is interesting and worth reporting because it may prove to be a
predictor of outcome. In our patients in whom evidence of viable hepatic
tissue or malignancy or both was present (60%), progression to irreversible
coagulation and cellular death might be found later after treatment if one
assumes that radiofrequency ablation causes hepatic injury and subsequent cell
necrosis in a pathophysiologic manner similar to that in ischemic necrosis
[13]. This question was not
addressed in our study, which did not include any late tissue evaluation from
the area of the ablated tumor. Several mechanisms may cause cellular injury by
radiofrequency ablation [14];
the most likely one would be due to radiofrequency-induced heating, which
presumably drives extracellular and intracellular water out of the tissue and
causes coagulation necrosis
[15]. Although reported for
the first time, finding coagulation necrosis immediately after ablation is not
surprising. Histopathologic findings 24 hr after radiofrequency ablation in a
rabbit liver model showed coagulation necrosis that could be detected on MRI
[16]. Coagulative necrosis
after radiofrequency ablation was described in a pig liver model
[17], and "coarcted
cytoplasm" (coagulation), in a guinea pig liver study
[18] within the first day
after ablation. When the researchers evaluated the effect of vascular
occlusion on radiofrequency ablation in a porcine model
[19], the animals were
immediately sacrificed after ablation, and specimen examination and H and E
staining showed that the liver area around the radiofrequency probe
(four-electrode probe, model 30, RITA Medical Systems) consisted of vacuolated
hepatocytes with frayed borders. In the inner zone of ablation around the
probe, no intact hepatic tissue was seen. Coagulated tissue with no viable
cells was found in the central pale zone of ablation in a porcine model after
using the LeVeen electrode (Radiotherapeutics)
[20]. When the researchers
used a similar technique with the hook electrodes probe (RITA Medical
Systems), the ablated liver tumor was resected and evaluated pathologically at
a later time. The results showed that in all cases, the ablated tissue could
be recognized on H and E–stained sections as areas of disrupted cell
outlines, preserved nuclear staining, and increased cytoplasmic eosinophilia
[21]. Tissue viability
immediately after radiofrequency ablation with the LeVeen probe in the normal
pig liver has been evaluated with histochemical (lactate dehydrogenase and
nicotinamide adenine dinucleotide-diaphorase-NADPH-diaphorase) and H and E
stains, showing a core of heat-coagulation tissue on the H and E not stained
by the histochemical stain, suggesting 100% cellular destruction
[22]. H and E staining showed
thermal coagulation in specimens collected 8 hr after radiofrequency ablation
of lung tumors in a large-animal model
[23]. Using this simple
technique, we showed that coagulation necrosis achieved by radiofrequency
ablation can be recognized immediately on pathologic examination of the
extracted tissue in almost half of the cases.
This preliminary report shows that tissue adherent to the radiofrequency
probe after ablation can be examined pathologically and may show coagulation
necrosis [22,
23]. Immediate postablation
pathologic examination of tissue adherent to the radiofrequency probe is
technically feasible and may instigate further investigation to determine its
value as a possible predictor of radiofrequency ablation outcomes.
References
- Gazelle GS, Goldberg SN, Solbiati L, Livraghi T. Tumor ablation
with radio-frequency energy. Radiology2000; 217:633
–646[Abstract/Free Full Text]
- Rhim H, Yoon K, Lee FM, et al. Major complications after
radio-frequency thermal ablation of hepatic tumors: spectrum of imaging
findings. RadioGraphics2003; 23:123
–136[Abstract/Free Full Text]
- Kato T, Tamura S, Tekin A, et al. Use of a microwave coagulation
therapy in liver transplant candidates with hepatocellular carcinoma: a
preliminary report. Transplant Proc2001; 33:1469[Medline]
- Dodd GD III, Soulen MC, Kane RA, et al. Minimally invasive
treatment of malignant hepatic tumors: at the threshold of a major
breakthrough. RadioGraphics2000; 20:9
–27[Abstract/Free Full Text]
- Goldberg SN, Charboneau JW, Dodd GD III, et al. Image-guided tumor
ablation: proposal for standardization of terms and reporting criteria.
Radiology2003; 228:335
–345[Abstract/Free Full Text]
- Pulvirenti A, Garbagnati F, Regalia F, et al. Experience with
radiofrequency ablation of small hepatocellular carcinomas before liver
transplantation. Transplant Proc2001; 33:1516
–1517[Medline]
- Curley SA, Izzo F, Ellis LM, et al. Radiofrequency ablation of
hepatocellular cancer in 110 patients with cirrhosis. Ann
Surg 2000;232:381
–391[Medline]
- Llovet JM, Vilana R, Bru C, et al. Increased risk of tumor seeding
after percutaneous radiofrequency ablation for single hepatocellular
carcinoma. Hepatology2001; 33:1124
–1229[Medline]
- Rossi S, Garbagnati F, Lencioni R, et al. Percutaneous
radio-frequency thermal ablation of nonresectable hepatocellular carcinoma
after occlusion of tumor blood supply. Radiology2000; 217:119
–126[Abstract/Free Full Text]
- Berber E, Flesher NL, Siperstein AE. Initial clinical evaluation of
the RITA 5-centimeter radiofrequency thermal ablation catheter in the
treatment of liver tumors. Cancer J2000; 6[suppl 4]:S319
–S329
- Lencioni R, Cioni D, Goletti O, Bartolozzi C. Radiofrequency
thermal ablation of liver tumors: state-of-the-art. Cancer
J 2000;6[suppl 4]:S304
–S315
- McGahan JP, Dodd G III. Radiofrequency ablation of the liver:
current status. AJR2001; 176:3
–16[Free Full Text]
- Goldberg SN, Gazelle GS, Compton CC, Mueller PR, Tanabe KK.
Treatment of intrahepatic malignancy with radiofrequency ablation:
radiologic-pathologic correlation. Cancer2000; 11:2452
–2463
- Haines D, Watson D. Tissue heating during radiofrequency catheter
ablation: a thermodynamic model and observations in isolated perfused and
superfused canine right ventricular free wall. Pacing Clin
Electrophysiol 1989;12:962
–976[Medline]
- Huang S. Advances in applications of radiofrequency current to
catheter ablation therapy. Pacing Clin Electrophysiol1991; 14:28
–42[Medline]
- Lee JD, Lee JM, Kim SW, Kim CS, Mun WS. MR imaging-histopathologic
correlation of radiofrequency thermal ablation lesion in a rabbit liver model:
observation during acute and chronic stages. Korean J
Radiol 2001;2:151
–158[Medline]
- Hansen PD, Rogers S, Corless CL, Swanstrom LL, Siperstien AE.
Radiofrequency ablation lesions in a pig liver model. J Surg
Res 1999;87:114
–121[Medline]
- Rossi S, Fornari F, Pathies C, Buscarini L. Thermal lesions induced
by 480 KHz localized current field in guinea pig and pig liver.
Tumori 1990;28;76:54
–57
- Chinn SB, Lee FT Jr, Kennedy GD, et al. Effect of vascular
occlusion on radiofrequency ablation of the liver: results in a porcine model.
AJR 2001;176:789
–795[Abstract/Free Full Text]
- Raman SS, Lu DK, Vodopich DJ, Sayre J, Lassman C. Creation of
radiofrequency lesions in a porcine model: correlation with sonography, CT,
and histopathology. AJR2000; 175:1253
–1258[Abstract/Free Full Text]
- Scudamore CH, Lee SI, Patterson EJ, et al. Radiofrequency ablation
followed by resection of malignant liver tumors. Am J
Surg 1999;5:411
–417
- Sugimori K, Morimoto M, Shirato K, et al. Radiofrequency ablation
in a pig liver model: effect of transcatheter arterial embolization on
coagulation diameter and histologic characteristics. Hepatol
Res 2002;24:164
–173[Medline]
- Ahrar K, Price RE, Wallace MJ, et al. Percutaneous radiofrequency
ablation of lung tumors in a large animal model. J Vasc Interv
Radiol 2003;14:1037
–1043[Medline]
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Abstract
Introduction
