Sentinel lymph node and prognostic factors in gastric cancer

Abstract

We would like to respond to the letter by Hanisch and Batsis entitled ‘‘Sentinel lymph node biopsy in laparoscopic surgical oncology’’ [1] in which some interesting concerns have been raised regarding the association of minimally invasive surgery and sentinel lymph node (SLN) navigation procedure described in our case report published in the September issue of Surgical Endoscopy [2]. In fact, there are several reservations in the application of SLN mapping in gastric cancer. Unexpected anatomical skip metastases might be accounted for by aberrant drainage routes from the primary lesion [3]. Unneglectable false-negative rates have been reported due to a number of factors. The most common one is the obstruction of lymphatic vessels due to cancer invasion. In these cases, the tracer is not able to reach the initial SLN and will be deviated to second tier or false SLNs. Other risk factors associated with false-negative SLN are surgeon inexperience, male gender, and a small number of SLNs (B3) [4]. The limitations of SLN navigation have been overcome with the restriction of its indication to early-stage cases, the introduction of technical improvements like the combination of dye-guided and radio-guided methods, and sentinel lymphatic basin dissection [5]. Some Eastern authors have proposed testing the SLN navigation association with conservative visceral resection such as function-preserving gastrectomy, endoscopic mucosal resection, or endoscopic submucosal dissection [6, 7]. This way, the morbidity and functional disturbances related to not only the extended lymphadenectomy but also to total or subtotal gastric resection are avoided. The attempts to reduce the adverse effects and invasiveness of early gastric cancer surgery are also translated in the association of SLN navigation with the laparoscopic procedure [8]. Such proposals should be substantiated by more consistent data. Reading carefully the letter of Hanisch and Batsis, it is possible to surmise that they did not see the possible operational or methodological caveats of our laparoscopic SLN navigation. Their final intention was not to discuss the conceptual limitations of the SLN procedure. The ultimate topic that they were trying to address was the lack of reliable prognostic markers in gastric cancer that would enable the correct modulation of surgical radicality in early-stage disease. They conclude that basic and translational research on genomics and epigenetics would provide not only the understanding of mechanisms underlying the tumor progression but also more robust predictive factors of long-term oncological outcome of gastric cancer. Gastric carcinogenesis is a multistep process involving genetic and epigenetic alteration of protein-coding proto-oncogenes and tumorsuppressor genes. Single nucleotide variants (SNVs), present as either germline or somatic point mutations, are essential drivers of tumorigenesis and cellular proliferation in many human cancer types because they were proven to be involved in DNA repair and tumor suppression [9]. Recent discoveries have shed new light on the involvement of a class of noncoding RNA known as microRNA (miRNA) in gastric cancer [10]. Genes coding these miRNAs have been characterized as novel protooncogenes and tumor-suppressor genes based on findings that these miRNAs control malignant phenotypes of gastric cancer cells. In this sense, miRNA dysregulation promotes cell-cycle progression [11], confers resistance to apoptosis [11, 12], and enhances invasiveness and metastasis [13]. Moreover, several miRNAs have also been shown to E. Orsenigo (&) S. Kusamura C. Staudacher Department of Surgery, University Vita-Salute San Raffaele, Via Olgettina, 60-20132 Milan, Italy e-mail: orsenigo.elena@hsr.it