139 Editorial (PRO/) CON: is STAS an inducible artifact? of signs of the suggested “vascular co-option” seen in most cases of purposed STAS, makes this observation unlikely to be a biological constant phenomenon. Possible alternative explanations For the observation “(i), the attachment to the alveolar wall”, gravity is likely to play a role, causing detached tumour cells to get in touch with alveolar walls. The term “in close approximation” to the alveolar wall, is scientifically probably more accurate than “attached” to the alveolar wall. For phrase “(ii) regarding replacement of pneumocytes”, an image is provided with a magnification220, that by itself is insufficient to judge the replacement of pneumocytes type I, because the alveolar wall including the pneumocytes type I at the gas exchange interface is very thin (between 0.2 and 0.6 μm). In the published figures, type I pneumocytes as an alternative explanation may be present in between the endothelial cell staining and the tumour cells. Thus, the scientific proof that IHC stains demonstrate the focal absence of pneumocytes at the “attachment points” is clearly lacking. For the phrase “(iii) dealing with the penetration of the alveolar wall”, in the provided image, an alternative explanation could be that this discontinuation may well correspond to physiological pores of Kohn222. In our opinion the suggestion that “tumour cells detach from the main tumour, migrate through air spaces, and reattach to the alveolar walls through vessel co-option, allowing them to survive and grow” is an overinterpretation or misconception, which is not incontrovertibly supported by the presented data. The argument of retained tumour cells in the unresected lobe after segmentectomy In a recent study Gross and colleagues observed that occult STAS tumour cells can be detected in the lung tissue of the remaining unresected lobe after segmentectomy199. Ten patients were examined who initially had a local resection with STAS and subsequently another local resection or a completion lobectomy. In all ten patients, STAS was found in the additional resection. As different knifes were used in the cases a strong argument is put forward against the pathologist’s knife as a plausible cause. The authors concluded that “our study provides evidence that STAS is not an ex-vivo artifact of the pathologic tissue-grossing process and adds to the growing evidence that STAS is an in vivo biological process.” However, if there are other explanations, the last interpretation is definitely a jump to far. An alternative explanation At this point it is essential to realize the physiology of the lymph flow in the lobes. A cross section of a lobe with subpleural lymph vessels is shown in Figure 3A. Columns of lymph are filled during inhalation in the lymph vessel, which are subsequently reduced in length during exhalation, pushing the lymphatic flow centrally, where the larger lymph vessels have valves. These prohibit backflow during the next inhalation. As the 11
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