Reply to Letter: “Neural Invasion Cannot be Controlled by Extended Surgery in Gastric Cancer”

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Reply:
In the presented study by Liebl et al,1 neural invasion of cancer cells was detected as an independent prognostic factor in gastric cancer. Here, they also demonstrate that the aggressiveness of cancer cells to invade nerves is even better represented by the individual neural invasion severity score, which in gastric cancer is not high and does not have a prognostic impact on survival. On the contrary, in the special subgroup of “gastric” cancer, the adenocarcinomas of the esophagogastric junction/AEG-II and III reveal a more aggressive neural invasion phenotype, with a distinct impact on patient's prognosis. With these data, it becomes obvious that the biological behavior of neural invasion varies in the different types of gastric cancer according to the site of the tumor and their differentiation. For this reason alone, a widely distributed extended gastric resection as suggested by Chen and colleagues2 cannot be fully supported. To justify such an aggressive surgical approach, we first have to better understand the pathogenesis of neural invasion in gastric cancer and why they differ within the same organ.
The importance of neural invasion in pancreatic cancer is nowadays a widely accepted phenomenon. This is also supported by recent data from Liebl et al, who demonstrated pancreatic cancer as the most neuroaffine cancer among all gastrointestinal malignancies. Indeed, in this study, pancreatic cancer had the greatest neural invasion severity and most dismal impact on patient's prognosis. According to the idea of Chen and colleagues, an extended resection in the case of pancreatic cancer may also lead to a better prognosis for this special subgroup of patients. Unfortunately, this is not the case. Jang et al3 have studied this approach especially with extended lymph node resection and extended resection at the superior mesenteric artery and coeliac plexus, with only disappointing results according to prognosis and survival. They concluded that extended resections with increased morbidities could not justify such an approach.
As surgeons we have to somehow accept that the feature of neural invasion is an oncological weapon that can hardly be overcome by the scalpel. We have to focus more on the pathogenesis of this phenomenon to understand its biological power. Until then, extended resections other than the already existing oncological resection concepts should be avoided.

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