Artículo Semana 03 (3 - )
Artículo Semana 03 (3 - )
Artículo Semana 03 (3 - )
1177/0284185116639765
Original Article
Acta Radiologica
0(0) 1–6
! The Foundation Acta Radiologica
Determination of the electrical 2016
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DOI: 10.1177/0284185116639765
impact on therapy planning in the acr.sagepub.com
Abstract
Background: Radiofrequency ablation is used to induce thermal necrosis in the treatment of liver metastases. The
specific electrical conductivity of a liver metastasis has a distinct influence on the heat formation and resulting tumor
ablation within the tissue.
Purpose: To examine the electrical conductivity s of human colorectal liver metastases and of tumor-free liver tissue in
surgical specimens.
Material and Methods: Surgical specimens from patients with resectable colorectal liver metastases were used for
measurements (size of metastases <30 mm). A four-needle measuring probe was used to determine the electrical
conductivity s of human colorectal liver metastasis (n ¼ 8) and tumor-free liver tissue (n ¼ 5) in a total of five patients.
All measurements were performed at 470 kHz, which is the relevant frequency for radiofrequency ablation. The tissue
temperature was also measured. Hepatic resections were performed in accordance with common surgical standards.
Measurements were performed in the operating theater immediately after resection.
Results: The median electrical conductivity s was 0.57 S/m in human colorectal liver metastases at a median tempera-
ture of 35.1 C and 0.35 S/m in tumor-free liver tissue at a median temperature of 34.9 C. The electrical conductivity was
significantly higher in tumor tissue than in tumor-free liver tissue (P ¼ 0.005). There were no differences in tissue
temperature between the two groups (P ¼ 0.883).
Conclusion: The electrical conductivity is significantly higher in human colorectal liver metastases than in tumor-free
liver tissue at a frequency of 470 kHz.
Keywords
Electrical conductivity, radiofrequency ablation, liver metastases
Date received: 26 October 2015; accepted: 17 February 2016
Introduction
Biological tissues have different electrical conductivities
Radiofrequency ablation (RFA) is a frequently used (6,7). Haemmerich et al. measured the electrical con-
treatment for primary liver tumors and liver metastases ductivity of a small number of human liver tumors
(1,2). A challenge in RFA is the induction of ablation and healthy liver tissue. They showed that the electrical
zones large enough to destroy the tumor tissue with an
adequate security margin to prevent local tumor recur-
rence. The mechanisms by which tissue is destroyed by Charité–Universitätsmedizin Berlin, Berlin, Germany
RFA are well known (3,4). The area of the induced
Corresponding author:
thermal necrosis is significantly influenced by the prop- Urte Zurbuchen, Charité–Universitätsmedizin Berlin, Campus Benjamin
erties of the treated tissue, such as blood flow in Franklin, Hindenburgdamm 30, Berlin, 12200, Germany.
the tissue (5) and its electrical conductivity (6). Email: urte.kunz-zurbuchen@charite.de
conductivity is higher in tumor tissue than in healthy accordance with common surgical standards. The
tissue, independent of the frequency used for measure- measurements were obtained in the operating room
ment. Any relationship between temperature and elec- immediately (3–5 min) after resection of the surgical
trical conductivity was not examined in this study (8). specimen.
In an earlier study, we examined the changes in elec- The four-needle measuring probe was positioned in
trical conductivity s during tissue coagulation at the the tumor (Figs. 1 and 2), and the electrical conductiv-
ablative and cooling temperatures associated with ity was read from the measurement bridge. The
RFA (9). We used porcine liver tissue in an ex vivo temperature of the tissue was measured with a digital
model for this study. We showed that the electrical thermometer in the middle of the tissue near the mea-
conductivity increased during the heating phase and suring probe. Measurements in macroscopic tumor-
decreased continuously during the cooling phase. In a free liver tissue were performed in a similar manner
pre-test, we completed a single conductivity measure- within the same surgical specimen. The surgical speci-
ment in a human liver sample to examine the electrical mens underwent a histological assessment after
conductivity in healthy human liver tissue and in a measurement.
human liver metastasis. This measurement indicated All data (tissue temperature, electrical conductivity,
that the electrical conductivity of human liver tissue is histological findings, and pre-treatment chemotherapy)
significantly different from that of porcine liver tissue. were collected in a database. Statistical analyses were
The conductivity was higher for the liver metastasis and
lower for the healthy liver tissue compared with the
corresponding values in the porcine liver at the same
temperature.
The aim of this study was to examine the electric
conductivity s of human colorectal liver metastases
and of tumor-free liver tissue in surgical specimens.
performed with IBM SPSS Statistics version 21 (IBM, electrical conductivity value was 0.35 S/m in the tumor-
Ehningen, Germany). Central tendencies were calcu- free liver tissue. The electric conductivity was signifi-
lated as medians (minimum – maximum) because cantly higher in the metastases than in the tumor-free
none of the parameters measured showed normal dis- liver tissue (Table 2).
tributions. The Mann–Whitney U Test was used for To examine whether a correlation between tempera-
comparisons between two independent groups. The ture and conductivity existed, we used Pearson’s correl-
level of significance was 0.05 (two-sided) for each stat- ation coefficient. The temperature difference was 2.1 C
istical test. To determine whether a linear correlation for liver metastases and 1 C for tumor-free liver tissue.
existed between temperature and conductivity, we used There was no significant correlation between tempera-
Pearson’s correlation coefficient. ture and conductivity in liver metastases or tumor-free
liver tissue (Pearson’s correlation: P ¼ 0.985 for liver
metastases and P ¼ 0.880 for tumor-free liver tissue).
Results
The measurements were obtained from human colorec-
tal liver metastases from five patients with a total of
Discussion
eight metastases. Measurements were also performed In this study, we examined the electrical conductivity s
in tumor-free liver tissues from all surgical specimens. in human colorectal liver metastases and in tumor-free
Table 1 shows the results of all electrical conductivity liver tissues from surgical specimens. We investigated
s measurements, including the temperature at the eight metastases in five patients. The median electrical
time of measurement. The postoperative histological conductivity s was 0.57 S/m at a median temperature of
examination confirmed colorectal adenocarcinomas 35.1 C for the metastases. This value was significantly
in all metastases. The tumor-free liver tissue samples higher than the electrical conductivity of the human
showed different grades of steatosis or fibrosis. The tumor-free liver tissue, which was 0.35 S/m at a tem-
measurements in all eight metastases were performed perature of 34.9 C.
at a median temperature of 35.1 C. The median elec- Previous studies in various tumor models suggested
trical conductivity s of the metastases was 0.57 S/m. that malignant tissue has a higher electrical conductiv-
The five measurements in healthy liver tissue were per- ity than normal tissues at radiofrequencies (11,13,14).
formed at a median temperature of 34.9 C. The median Haemmerich et al. measured electrical conductivity in a
Table 1. Electrical conductivity in colorectal liver metastases and tumor-free liver tissue.
Group
small number of human liver tumors and healthy liver the measurements were essentially performed at body
tissue samples. These authors showed that the electrical temperature. Cell disintegration could be excluded, as
conductivity is higher in tumor tissue than in healthy all measurements were performed without delay after
tissue, independent of the frequency used for measure- resection.
ment (8). The relationship between temperature and However, this study also had some limitations. In
electrical conductivity was not examined in this study. addition to the small sample size, we measured the con-
In this study, the measurements were performed ductivity in liver tissue at only one specific temperature
30–60 min after resection of the surgical specimen and after surgical resection. Therefore, we could not exam-
after the transport of tissues to the pathology lab, ine temperature-dependent changes, which we expect to
where the tumor was centrally sliced to expose the occur during RFA. While these data would be interest-
tumor core. Haemmerich determined the electrical con- ing, such an approach is limited due to ethical consid-
ductivity to be 0.50 S/m for tumor tissue and 0.26 S/m erations. An experimental conductivity measurement
for normal liver tissue at 460 kHz. The temperature of involving the coagulation process would require heat-
the tissue upon measurement was not indicated. Our ing of the tumor (9), which would render a proper
results at 470 kHz, which were 0.57 S/m for tumor tis- pathological investigation impossible. The vasculariza-
sues and 0.35 S/m for normal liver tissue, are slightly tion of tissue was missing in our study. It is known that
higher than the values obtained by Haemmerich. Our the vascular perfusion of tissue has a high impact on its
results confirm that the electrical conductivity is higher biophysiological properties (5). The absence of blood
in tumor tissue than in normal tumor-free tissue. We flow in the measured tissue presumably influences the
assumed that the slightly greater electrical conductivity electrical conductivity. In our previous study, we
in our study was due to the higher temperature in the showed temperature-dependent changes in electrical
tissue at the time of measurement. In our experimental conductivity during the complete heating and cooling
set-up, the measurements were performed 3–5 min after phases within the RFA temperature range. We used
resection of the surgical specimen in the operating porcine liver samples for these ex vivo measurements.
room, and the tissue temperature was measured. In the present study, the temperature difference was
Empirical surgical specimens cool down quickly, 2.1 C for the liver metastases and 1 C for the tumor-
so we assume that the tissue temperatures in free liver tissue. There was no significant correlation
Haemmerich’s study were lower. between temperature and conductivity in our study.
In a previous study on porcine liver ex vivo, we Even if we did not examine the changes in electrical
determined that the electrical conductivity changes conductivity in human liver metastases during the
during the coagulation process (9). We showed that RFA heating and cooling phases for the reasons out-
the electrical conductivity s depends on the tissue tem- lined above, we assumed that the trends would be the
perature and that the conductivity continuously same and that the electrical conductivity would increase
increases during the thermal coagulation process. The during the heating phase and decrease continuously
maximum conductivity was reached at a temperature of during the cooling phase. Other experimental studies
80 C. During the cooling phase, which follows coagu- support this statement (15).
lation, the electrical conductivity was uniformly lower The heat dispersion during RFA of colorectal liver
than that during tissue heating. To our knowledge, no metastases is influenced by several application param-
data exist regarding the correlation between electrical eters (applicator length, power settings, application
conductivity s and tissue temperature in human colo- time), as well as by tissue-dependent parameters
rectal liver metastases. (16,17). In addition to vascular perfusion (5), electrical
All measurements were performed in the operating conductivity determines the depth of the heat disper-
room immediately after surgical resection to ensure that sion in the target tissue. Several studies have shown that
larger coagulation zones can be achieved by changing 2. Cirocchi R, Trastulli S, Boselli C, et al. Radiofrequency
the biophysiological properties of the target tissue ablation in the treatment of liver metastases from colo-
(18,19). Based on the knowledge that a change in elec- rectal cancer. Cochrane Database Syst Rev Online 2012;
trical conductivity can be achieved by saline, the per- 6:CD006317.
fusion of saline in the vicinity of radiofrequency 3. Goldberg SN, Gazelle GS, Compton CC, et al.
Treatment of intrahepatic malignancy with radiofre-
applicators has been performed to produce larger
quency ablation: radiologic-pathologic correlation. Cancer
coagulation zones (20) and maintain low electrical
2000;88:2452–2463.
conductivity. 4. Thomsen S. Pathologic analysis of photothermal and
Differences in the electrical conductivity between photomechanical effects of laser-tissue interactions.
liver metastases and tumor-free liver tissue can have a Photochem Photobiol 1991;53:825–835.
significant impact on ablation area. The histological 5. Lehmann KS, Ritz JP, Valdeig S, et al. Ex situ quantifi-
analysis of the liver tissue samples in our study showed cation of the cooling effect of liver vessels on radiofre-
different stages of steatosis or fibrosis. The impact of quency ablation. Langenbecks Arch Surg Dtsch Ges Für
liver histological features on the electrical conductivity Chir 2009;394:475–481.
of the tissue is not clear. An impedance-controlled 6. O’Rourke AP, Lazebnik M, Bertram JM, et al. Dielectric
therapy, which takes the changes in electrical conduct- properties of human normal, malignant and cirrhotic
ivity into account, would be a reasonable approach liver tissue: in vivo and ex vivo measurements from 0.5
for an optimized ablation strategy (21). Moreover, com- to 20 GHz using a precision open-ended coaxial probe.
puter-aided simulation and planning tools are being Phys Med Biol 2007;52:4707–4719.
7. Fu F, Xin SX, Chen W. Temperature- and frequency-
developed to enable a pre-interventional estimation of
dependent dielectric properties of biological tissues
RFA effectiveness (22,23) by using mathematical simu-
within the temperature and frequency ranges typically
lation to model the electrical conductivity of tissues (24). used for magnetic resonance imaging-guided focused
The simulation algorithms of these systems require ultrasound surgery. Int J Hyperth Off J Eur Soc
information related to the electrical conductivity of Hyperthermic Oncol North Am Hyperth Group 2014;
target tissues for precise RFA therapy planning. 30:56–65.
In conclusion, electrical conductivity significantly 8. Haemmerich D, Schutt DJ, Wright AW, et al. Electrical
differs between human colorectal liver metastases and conductivity measurement of excised human metastatic
tumor-free liver tissue. The conductivity influences the liver tumours before and after thermal ablation. Physiol
energy distribution in the target tissue during RFA. Meas 2009;30:459–466.
Knowledge of the conductivity can have an impact on 9. Zurbuchen U, Holmer C, Lehmann KS, et al.
RFA and can be used to optimize therapy planning. Determination of the temperature-dependent electric
The higher electrical conductivity of tumor tissue conductivity of liver tissue ex vivo and in vivo:
should be considered in planning algorithms for Importance for therapy planning for the radiofrequency
ablation of liver tumours. Int J Hyperth Off J Eur Soc
RFA. A viable option would be to directly measure
Hyperthermic Oncol North Am Hyperth Group 2010;26:
the specific conductivity before RFA. The ablation
26–33.
could then be performed in an impedance-controlled 10. Tsai JZ, Cao H, Tungjitkusolmun S, et al. Dependence of
manner to reach an optimal energy input into the apparent resistance of four-electrode probes on insertion
target tissue. depth. IEEE Trans Biomed Eng 2000;47:41–48.
11. Haemmerich D, Ozkan R, Tungjitkusolmun S, et al.
Declaration of conflicting interests Changes in electrical resistivity of swine liver after occlu-
sion and postmortem. Med Biol Eng Comput 2002;40:
The authors declared no potential conflicts of interest with
29–33.
respect to the research, authorship, and/or publication of this
12. Haemmerich D, Staelin ST, Tsai JZ, et al. In vivo elec-
article.
trical conductivity of hepatic tumours. Physiol Meas
2003;24:251–260.
Funding 13. Surowiec AJ, Stuchly SS, Barr JB, et al. Dielectric prop-
The authors received no financial support for the research, erties of breast carcinoma and the surrounding tissues.
authorship, and/or publication of this article. IEEE Trans Biomed Eng 1988;35:257–263.
14. Swarup A, Stuchly SS, Surowiec A. Dielectric properties
of mouse MCA1 fibrosarcoma at different stages of
References development. Bioelectromagnetics 1991;12:1–8.
1. Faitot F, Faron M, Adam R, et al. Two-stage hepatect- 15. Wi H, McEwan AL, Lam V, et al. Real-time conductivity
omy versus 1-stage resection combined with radiofre- imaging of temperature and tissue property changes
quency for bilobar colorectal metastases: a case-matched during radiofrequency ablation: an ex vivo model using
analysis of surgical and oncological outcomes. Ann Surg weighted frequency difference. Bioelectromagnetics 2015;
2014;260:822–827. (discussion 827–828). 36:277–286.
16. Zurbuchen U, Frericks B, Roggan A, et al. Ex vivo evalu- output more effective? RöFo Fortschritte Auf Dem
ation of a bipolar application concept for radiofrequency Geb Röntgenstrahlen Nukl 2007;179:282–288.
ablation. Anticancer Res 2009;29:1309–1314. 21. Kröger T, Pätz T, Altrogge I, et al. Fast estimation of the
17. Vahldiek JL, Lehmann KS, Poch F, et al. Measuring vascular cooling in RFA based on numerical simulation.
and optimizing results in multipolar RFA: Techniques Open Biomed Eng J 2010;4:16–26.
and early findings in an experimental setting. Clin 22. Rieder C, Kroeger T, Schumann C, et al. GPU-based
Hemorheol Microcirc 2014;58:77–87. real-time approximation of the ablation zone for radio-
18. Goldberg SN, Ahmed M, Gazelle GS, et al. Radio- frequency ablation. IEEE Trans Vis Comput Graph
frequency thermal ablation with NaCl solution injec- 2011;17:1812–1821.
tion: effect of electrical conductivity on tissue heating 23. Lehmann KS, Frericks BB, Holmer C, et al. In vivo val-
and coagulation-phantom and porcine liver study. idation of a therapy planning system for laser-induced
Radiology 2001;219:157–165. thermotherapy (LITT) of liver malignancies. Int J
19. Liu Z, Ahmed M, Weinstein Y, et al. Characterization of Colorectal Dis 2011;26:799–808.
the RF ablation-induced ‘‘oven effect’’: the importance of 24. Trujillo M, Berjano E. Review of the mathematical func-
background tissue thermal conductivity on tissue heating. tions used to model the temperature dependence of elec-
Int J Hyperth Off J Eur Soc Hyperthermic Oncol North trical and thermal conductivities of biological tissue in
Am Hyperth Group 2006;22:327–342. radiofrequency ablation. Int J Hyperth Off J Eur Soc
20. Clasen S, Geng A, Herberts T, et al. Internally cooled Hyperthermic Oncol North Am Hyperth Group 2013;
bipolar radiofrequency ablation: is a lower power 29:590–597.