The visceral pleura, lung cancer and lymphatic spread

The paper by Takeda et al. in this month’s EJCTS explores the channels of lymphatic spread in lung cancer cases with visceral pleural invasion [1]. There is a lot going on in this paper with a collection of very interesting messages.

All surgeons make conscious or unconscious visual judgements of the quality of the lung during lung surgery. We all register levels of surface anthracosis and automatically draw assessments regarding lung function and lung quality. However, we do not currently draw conclusions on cancer spread from that same information. The authors of this study suggest we should.

In this paper, the authors do a number of interesting things. They bring in visual assessment of the lung with a mix of subjective and objective measures. In 2022, image software should permit objective scientific assessment and the use of such tools should be encouraged. In this paper, the authors do use subjective measures of anthracosis; two surgeons subjectively score the level of anthracosis on a simple rating scale. However, they also use an objective assessment with an image software processing package which was used to generate an anthracotic ratio (%). This greatly strengthens the study and the potential reproducibility of the study. Ultimately the development of this type of image processing software could be incorporated into a Video Assisted Thoracoscopic Surgery (VATS) or Robotic Assisted Thoracoscopic Surgery (RATS) system, generating useful data for the operating surgeon.

The authors attempt to map in real time the lymphatic drainage patterns of the visceral pleura with an image processing assessment tool. They use Indocyanine Green (ICG) dye injection with video fluoroscopy to image and track the passage of dye through lymphatic channels. At least we think that it how it clears, as it is not clear how much drains by the venous system. There is an opportunity here for future studies to use objective image analysis software to profile this lymphatic transit, although in this study it was assessed subjectively by a surgeon.

The histology of cases with high levels of anthracosis shows distinctive lymphatic anatomy. Cases with high levels on anthracosis have different lymphatic patterns. What is not clear is if the changes in lymphatic anatomy that have impaired lymphatic drainage are initiated and driven by the anthracosis. It remains possible that patients with congenitally poor lung visceral pleural lymphatic drainage are the cases that accumulate the debris of anthracosis, rather than clear it. There is potentially much basic science to explore in understanding which is the chicken and egg here. Ultimately for an operating surgeon, there may now be an intraoperative visual measure (anthracosis score) that communicates lymphatic spread patterns in lung cancer with immediate operative implications in regard to lymph node assessment.

For the operating surgeon, a full lymph node assessment and clearance remains the gold standard and this paper does not change that. However, there are two interesting messages from this paper in regard to lymphatic spread. First, this paper further develops the understanding of lymphatic drainage. Not only does the lung parenchyma drain in a sequential pattern through the lymph nodes that we surgeons name N1 and then to N2 nodes, but rather some of the lymphatic drainage channels along the visceral pleural directly to N2 nodes bypassing what we label N1 nodes. Second, this has cancer implications in that pleural positive tumours have two channels to N2 nodes: within the lung via N1 nodes and along the visceral pleura surface, bypassing N1 nodes. This should remind us of the established truth of the weakness of any limited lymph node assessment. The lung cancer staging project upgrades small tumours with pleural invasion to T2. While many would view the adverse mechanism as shedding tumour cells into the pleural space and contact with the corresponding parietal pleura, the visceral pleural lymphatic drainage to N2 nodes may also be a factor in the unfavourable prognosis noted with visceral pleural invasion.

Ironically, if we accept that anthracotic lung appearances correlate with high exposure to airborne particles; we would expect that to be bad. However, it almost seems in this case that a low anthracotic score may leave an individual more vulnerable to N2 node positivity, although that is probably an over interpretation.

There are some weaknesses in this paper. One study group consists of only 42 cases collected over 7 years (6/year) and the other 53 cases collected over 9 years (6/year). Some of the key results depend on the subjective reports of two surgeons. In many ways, not using the image analysis software for the ICG analysis was a missed opportunity.

Overall this is a very stimulating paper with a number of potential follow-through inquiries. The use of objective image analysis software is possible in 2022, and to be encouraged. I would have liked if the authors had continued their use of objective image software for the ICG assessment, in addition to the anthracosis score. They also leave a 5-min interval between injection and ICG measurement, and it is unclear what impact that had on clearance in the anthracotic group. Studies using ICG imaging will be limited by the ability of the fluoroscopy to penetrate into tissues and so further development of this research theme may require evolving techniques or animal studies.

For those working in lung cancer, this is an interesting paper pushing us to explore the basic science of pulmonary lymphatic drainage. Does the anthracosis cause the distinctive lymphatic anatomy and performance patterns or were they the reason for the retention of the anthracotic debris? We always think of the inhaled debris as toxin drivers of neoplasia, but what if they also altered the lymphatic drainage? Does intraoperative assessment of anthracosis offer a novel real-time guide for the surgeon in regard to the surgical approach? How can we use contemporary image software analysis to more accurately and objectively assess the lungs we operate on, in an era when most surgeons observe the lung through a camera? Isn't this the most fantastic and fascinating discipline to work in! There is much still to learn. We must endeavour.

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