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Dig Surg. 2009 December; 26(5): 434–435.
Published online 2009 November 13. doi:  10.1159/000235955
PMCID: PMC2826428

Re: Assessment of Viable Tumour Tissue Attached to Needle Applicators after Local Ablation of Liver Tumours

Dear Sir,

We have read with great interest the paper by Snoeren et al., entitled ‘Assessment of viable tumour tissue attached to needle applicators after local ablation of liver tumours’ [1] . The authors commented that the finding in our earlier publication [2] where intact tumor cells were detected by simple HE examinations on tissue extracted on the RITA Starburst XL electrode after ablation of liver malignancies is remarkable. This finding was not in accordance with their findings where viable tumor was only found on the Leveen Radiotherapeutics device [1] . In order to improve the limitations of morphologic stains a lone in our initial study [2], we performed evaluation of fixed specimens with proliferation marker Ki67 [3, 4] and apoptosis marker caspase 3 [5]. This study [6] demonstrated that tumor cells positive for Ki67 carry a risk of approximately 6 times for local tumor progression (LTP) when compared to those that are Ki67-negative (hazard ratio 5.9, 95% CI 2.4-14.5, p <0.001). Furthermore, for the subset of tumors under 3 cm in largest diameter, this risk is over 10 times for the Ki67-positive tumor cells when compared to those that test negative (hazard ratio 10.1, 95% CI 1.7-57.5, p = 0.009). In this study, we collected specimens after RF ablation with the Leveen (n = 54) and the RITA XL (n = 14) electrodes [6]. 13/68 (19%) specimens were positive for Ki67, 12/54 (22.2%) from the Leveen and 1/14 (7%) from the RITA electrode. This difference was not statistically significant (p = 0.27). Should this trend remain the same, a statistically significant difference could be established if the population was 250.

We have certain questions regarding the methodology of Snoeren et al. [1]:

  • (1) Is it possible that any cells reacting to the G6PD were normal viable hepatocytes and not tumor?
  • (2) Macroscopic tissue adherent on RITA electrodes was seen in 87.5% cases. Did all these specimens contain completely destructed, nonidentifiable cells? Were there any nests of identifiable tumor cells with or without changes of thermal injury?
  • (3) It appears that tissue was found in 7/8 cases (87.5%) treated with the RITA electrode. Is it possible that the differences in the incidence of viable tumor cells between electrodes would be different with the addition of more cases?
  • (4) The inability to resect with a clear, tumor-free margin, and multifocal and extrahepatic disease were indications for ablation. Was the ratio of patients with these factors similar between the groups that were treated with the Leveen when compared to the other electrodes? (5) Are the authors planning to report on the incidence of LTP and track seeding in their population in order to identify any correlation with their tissue findings?

Several publications evaluating tissue changes after ablation in animal tumor models [7, 8] and human hepatic malignant tumors [9, 10] have demonstrated that the presence of tumor cells in the HE stain corresponds to viable tumor. In our publication, identifiable tumor cells were examined with proliferation marker Ki67, confirming the proliferation and viability of those cells [6] . Tumor cells were more commonly identified after the use of the Leveen when compared to the Starburst Xl electrode; however, this difference was not significant [6] . The presence of Ki67-positive tumor cells on tissue extracted on the electrode was identified as an independent prognostic risk factor of LTP as mentioned above [6] . This marker as well as caspase 3 can be evaluated in fixed specimens allowing evaluation of the same tumor cells identified with the HE stains.

Snoeren et al. [1] attributed their findings to the inability to perform track ablation with the Leveen electrode after treatment. Although this is an important point and may be related to the presence of viable tumor in their series, no viable tumor should remain on the electrode if ablation of the tumor with creation of an adequate clear margin was successful. It is therefore important to select patients for ablation when tumor treatment with a clear margin can indeed be reasonably achieved. In any other case, ablation should not be offered with a curative intent.

The performance of tissue examinations in the ablated tumors is important to confirm coagulation necrosis or detect residual viable tumor, able to proliferate. This may allow identification of patients at risk of LTP and additional treatment that may improve outcomes.

Footnotes

Disclosure Statement

C.T.S., L.P. and M.G. received research support from the National Institute of Health (R21-CA131763) for research related to this publication.

References

1. Snoeren N, Jansen MC, Rijken AM, van Hillesgersberg R, Slooter G, Klaase J, van der Tol PM, van der Linden E, Ten Kate FJW, van Gulik TM. Assessment of viable tumour tissue attached to needle applicators after local ablation of liver tumours. Dig Surg. 2009;26:56–62. [PubMed]
2. Sofocleous CT, Klein KM, Hubbi B, Brown KT, Weiss SH, Kannarkat G, Hinrichs CR, Contractor D, Bahramipour P, Barone A, Baker SR. Histopathologic evaluation of tissue extracted on the radiofrequency probe after ablation of liver tumors: preliminary findings. AJR Am J Roentgenol. 2004;183:209–213. [PubMed]
3. Scalzo DA, Kallakury BV, Gaddipati RV, Sheehan CE, Keys HM, et al. Cell proliferation rate by MIB-1 immunohistochemistry predicts postradiation recurrence in prostatic adenocarcinomas. Am J Clin Pathol. 1998;109:163. [PubMed]
4. Scholzen T, Gerdes J. The Ki-67 protein: from the known and the unknown. J Cell Physiol. 2000;182:311–322. [PubMed]
5. Budihardjo I, Oliver H, Lutter M, Luo X, Wang X. Biochemical pathways of caspase activation during apoptosis. Annu Rev Cell Dev Biol. 1999;15:269–290. [PubMed]
6. Sofocleous CTNR, Petrovic L, Klimstra D, Gonen M, Brown KT, Brody LA, Covey AM, Thornton R, Fong Y, Solomon SB, Schwartz L, DeMatteo R, Getrajdman GI. Hi stopat hologic and immunohistochemical features of tissue a dherent to multitined electrodes after RF ablation of liver malignancies can help predict local progression: initial results. Radiology. 2008;249:364–374. [PubMed]
7. Raman SS, Lu DS, Vodopich DJ, Sayre J, Lassman C. Creation of radiofrequency lesions in a porcine model: correlation with so nography, CT, and histopathology. AJR Am J Roentgenol. 2000;175:1253–1258. [PubMed]
8. 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. [PMC free article] [PubMed]
9. Morimoto M, Sugimori K, Shirato K, et al. Treatment of hepatocellular carcinoma with radiofrequency ablation: radiologic-histo-logic correlation during follow-up periods. Hepatology. 2002;35:1467–1475. [PubMed]
10. Scudamore CH, Lee SI, Patterson EJ, et al. Radiofrequency ablation followed by resection of malignant liver tumors. Am J Surg. 1999;177:411–417. [PubMed]

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