137 Editorial (PRO/) CON: is STAS an inducible artifact? Figure 4. Example of an impression by a surgical pincet in an open lung biopsy taken for diagnosis of interstitial lung disease. The pincet marks are visible with adjacent crushed tissue and iatrogenic collapsed alveolar walls. Displacement during surgery handling Another possible cause of iatrogenic displacement of tumour cells is manipulation of the tumour during surgery or grossing of the fresh (unfixed) specimen. A ‘no touch’ technique is impossible during lung surgery or pathology grossing. During surgery not only clamping may be a cause, but also manipulation with a hand or an instrument (e.g., for tearing parenchyma into the clamp) (Figure 4). Moreover, opening of the thorax will abrogate the negative pressure between the parietal and visceral pleural leaves. This will reduce the physiologic lymph flow and thereby increase the interstitial pressure. The deflation process may have an incremental effect on the (also intratumorally) interstitial pressure. This process, combined with possible manipulation, may lead to an increase of circulating tumour cells (CTCs)207. Although studies on CTC’s during surgery for NSCLC collect blood samples at various sites (peripheral vein, radial artery during anaesthesia, pulmonary draining vein in the beginning and at the end of resection) and examine different biomarkers, the findings point more or less in the same direction: increase in CTCs during surgery208 209 210 211 212 213, increase in clusters of CTC128 212 214, association with adverse clinicopathologic parameters: higher stage215 212, microscopic lymphatic tumour invasion209, N+ vs N0215, reduced disease free survival216 217 218. Several manuscripts mention the word manipulation explicitly, expressing awareness in the surgical community. Moreover, the finding of normal epithelial cells in the pulmonary vein was also reported in a few 11
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