RESUMO
Palmitoylethanolamide (PEA) is an endocannabinoid-like bioactive lipid mediator belonging to the family of N-acylethanolamines, most abundantly found in peanuts and egg yolk. When the gastrointestinal (GI) effects of PEA are discussed, it must be pointed out that it affects intestinal motility but also modulates gut microbiota. This is due to anti-inflammatory, antioxidant, analgesic, antimicrobial, and immunomodulatory features. Additionally, PEA has shown beneficial effects in several GI diseases, particularly irritable bowel syndrome and inflammatory bowel diseases, as various studies have shown, and it is important to emphasize its relative lack of toxicity, even at high dosages. Unfortunately, there is not enough endogenous PEA to treat disturbed gut homeostasis, even though it is produced in the GI tract in response to inflammatory stimuli, so exogenous intake is mandatory to achieve homeostasis. Intake of PEA could be through animal and/or vegetable food, but bearing in mind that a high dosage is needed to achieve a therapeutic effect, it must be compensated through dietary supplements. There are still open questions pending to be answered, so further studies investigating PEA's effects and mechanisms of action, especially in humans, are crucial to implementing PEA in everyday clinical practice.
RESUMO
Pathologic complete response (pCR) after neoadjuvant systemic therapy (NAST) of early breast cancer (EBC) has been recognized as a good prognostic factor in the treatment of breast cancer because of its significant correlation with long-term disease outcome. Based on this correlation, pCR has been accepted by health authorities (FDA, EMA) as a surrogate endpoint in clinical trials for accelerated drug approval. Moreover, in recent years, we have observed a tendency to treat pCR in routine clinical practice as a primary therapeutic target rather than just one of the pieces of information obtained from clinical trials. These trends in routine clinical practice are the result of recommendations in treatment guidelines, such as the ESMO recommendation " to deliver all planned (neoadjuvant) treatment without unnecessary breaks, i.e. without dividing it into preoperative and postoperative periods, irrespective of the magnitude of tumor response", because " this will increase the probability of achieving pCR, which is a proven factor for a good prognosis ". We hypothesize that the above recommendations and trends in routine clinical practice are the consequences of misunderstanding regarding the concept of pCR, which has led to a shift in its importance from a prognostic factor to a desired treatment outcome. The origin of this misunderstanding could be a strong subconscious incentive to achieve pCR, as patients who achieved pCR after NAST had a better long-term outcome compared with those who did not. In this paper, we attempt to prove our hypothesis. We performed a comprehensive analysis of the therapeutic effects of NAST and adjuvant systemic therapy (AST) in EBC to determine whether pCR, as a phenomenon that can only be achieved at NAST, improves prognosis per se. We used published papers as a source of data, which had a decisive influence on the formation of the modern attitude towards EBC therapy. We were unable to find any evidence supporting the use of pCR as a desired therapeutic goal because NAST (reinforced by pCR) was never demonstrated to be superior to AST in any context.
