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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’  . The authors commented that the finding in our earlier publication  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  . In order to improve the limitations of morphologic stains a lone in our initial study , we performed evaluation of fixed specimens with proliferation marker Ki67 [3, 4] and apoptosis marker caspase 3 . This study  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 . 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. :
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  . 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  . 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  . 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.  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.
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.