Correspondence

We thank Drs. Caturelli and Ghittoni for drawing attention to our study. We are, however, unsure if due diligence was given to the review and interpretation of our article. Caturelli and Ghittoni contend that the incidence of hepatocellular carcinoma (HCC) among indeterminate nodules in our study is too low. As mentioned in the Discussion section, our reported incidence of 13%-24% is well within the range of 9%-33% reported by three European studies.1 The reason for the low incidence is the more sensitive imaging diagnostic criteria for 1-2 cm HCC in the updated American Association for the Study of Liver (AASLD) guidelines, where now one of two, rather than both, positive contrast imaging scan is required for diagnosis of malignancy.2 Furthermore, their suggestion that a smaller criterion for nodule growth than our 30% increase in diameter be used is highly unrealistic, given inter- and intraobserver variability for measuring 1-2 cm nodules. Precisely for this reason were the Response Evaluation Criteria In Solid Tumors (RECIST) criteria revised to the current 1.1 version. A criterion of a minimum of 5 mm growth in the single largest diameter of target lesion was added to avoid interpreting measurement error in small lesions as progressive disease.3 Caturelli and Ghittoni indicate puzzlement as to why some of our nodules were not visible on grayscale ultrasound. We have described in our methodology the realistic inclusion of nodules that were found on subsequent computed tomography (CT)/magnetic resonance imaging (MRI) work-up imaging. Additionally, the authors misinterpreted the aim of our study, which was to identify variables with significant association with HCC that would allow selective application of biopsy to a subset of indeterminate 1-2 cm nodules. Our aim was not to measure the impact of biopsy. Finally, biopsy sampling error is expected for such small nodules and that is why the AASLD guidelines ignore negative biopsies and recommend close follow-up or rebiopsy.2 Forner et al.4 reported 30% and 39% false-negative biopsy rates for first and second biopsies of HCCs. We want to vigorously stress that the aim of oncology is not the successful treatment of tumors, as Caturelli and Ghittoni suggest, but rather increasing patient survival. The treatment of “very early HCCs” has not been studied in such a way. When the majority of indeterminate nodules remain stable in the long-term, it is reasonable to limit biopsy and treatment to those who are predisposed to growth while closely following the others. Korosh Khalili M.D.*, Morris Sherman M.D. , * Department of Medical Imaging, University of Toronto, University Health Network, Princess Margaret Hospital, Toronto, ON, Canada, Department of Gastroenterology, University of Toronto, University Health Network, Princess Margaret Hospital, Toronto, ON, Canada.

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