Thyroid is at the crossroads of immune dysregulation, tissue remodeling and oncogenesis. Autoimmune disorders, nodular disease and cancer of the thyroid affect a large amount of general population, mainly women. We wondered if there could be a common factor behind three processes (immune dysregulation, tissue remodeling and oncogenesis) that frequently affect, sometimes coexisting, the thyroid gland. The long pentraxin 3 (PTX3) is an essential component of the humoral arm of the innate immune system acting as soluble pattern recognition molecule. The protein is found expressed in a variety of cell types during tissue injury and stress. In addition, PTX3 is produced by neutrophils during maturation in the bone-marrow and is stored in lactoferrin-granules. PTX3 is a regulator of the complement cascade and orchestrates tissue remodeling and repair. Preclinical data and studies in human tumors indicate that PTX3 can act both as an extrinsic oncosuppressor by modulating complement-dependent tumor-promoting inflammation, or as a tumor-promoter molecule, regulating cell invasion and proliferation and epithelial to mesenchymal transition, thus suggesting that this molecule may have different functions on carcinogenesis. The involvement of PTX3 in the regulation of immune responses, tissue remodeling and oncosuppressive processes led us to explore its potential role in the development of thyroid disorders. In this review, we aimed to highlight what is known, at the state of the art, regarding the connection between the long pentraxin 3 and the main thyroid diseases i.e., nodular thyroid disease, thyroid cancer and autoimmune thyroid disorders.

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Multimodal treatments are the gold standard for advanced resectable gastroesophageal cancer. The exclusive neoadjuvant, chemoradiation-based CROSS regimen and the perioperative chemotherapy-based FLOT regimen are commonly adopted for adenocarcinoma of distal esophagus and esophago-gastric junction (EGJ). At present, there is no clear evidence of the superiority of either of these two approaches on survival. An intention-to-treat analysis was performed on a cohort of consecutive patients who underwent neoadjuvant CROSS or FLOT regimen and subsequently confirmed to curative-intent surgery for adenocarcinoma of distal oesophagus and EGJ between August 2017 and October 2021. Propensity Score Matching (PSM) was performed in order to balance baseline characteristics of patients undergoing CROSS and FLOT neoadjuvant regimen. The primary endpoint was Overall Survival (OS). Secondary endpoints included Disease-Free Survival (DFS), 90-day morbidity rate, margin status, incidence and pattern of recurrence. Subgroup analyses were performed according to the specific neoadjuvant regimen adopted. Of the 111 patients included, 84 were correctly matched after PSM, 42 in each group. CROSS and FLOT patients showed similar 1-year OS rate (85.3% and 85.4% respectively, p = 0.189) and 1-year DFS rate (73.3% and 81.3% respectively, p = 0.267). When compared to FLOT patients, CROSS patients reported lower but not significant rates of post-operative severe complications (4.8% vs 11.9%, p = 0.433) and negative margins of resection (95.2% vs 97.6%, p = 1.000). In the CROSS group, 89% of recurrences occurred outside the radiation field. In FLOT group, 69% of patients completed all the 8 expected perioperative cycles. FLOT and CROSS offer similar OS and DFS, together with comparable 90-day morbidity/mortality rates and pathological findings. Both regimens are affected by specific limitations that have to be kept in mind during treatment assessment. The results of ongoing Randomized Controlled Trials are urgently awaited.

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