Current Knowledge on Endocrine Disrupting Chemicals (EDCs) from Animal Biology to Humans, from Pregnancy to Adulthood: Highlights from a National Italian Meeting

Wildlife has often presented and suggested the effects of endocrine disrupting chemicals (EDCs). Animal studies have given us an important opportunity to understand the mechanisms of action of many chemicals on the endocrine system and on neurodevelopment and behaviour, and to evaluate the effects of doses, time and duration of exposure. Although results are sometimes conflicting because of confounding factors, epidemiological studies in humans suggest effects of EDCs on prenatal growth, thyroid function, glucose metabolism and obesity, puberty, fertility, and on carcinogenesis mainly through epigenetic mechanisms. This manuscript reviews the reports of a multidisciplinary national meeting on this topic

I DISORDINI DELLO SVILUPPO SESSUALE E LE MALFORMAZIONI DELL’APPARATO GENITALE

La differenziazione sessuale è un processo complesso, che si articola durante tutta l’embriogenesi portando allo sviluppo di differenti tipologie di “sesso”. L’evoluzione naturale del sistema riproduttivo porta di default alla formazione di gonadi e genitali esterni femminili. Perché si compia la differenziazione in senso “maschile” sono necessari vari cofattori quali un gene SRY correttamente funzionante, tessuto gonadico che produca AMH e testosterone, recettori ormonali funzionanti nei tessuti bersaglio. Eventuali alterazioni di questo delicato processo possono portare alla presenza di Disordini dello Sviluppo Sessuale (DSD). Le malformazioni dell’apparato genitale (MAG) sono deviazioni dalla normale anatomia che possono ridurre la capacità riproduttiva di una donna o, in casi complessi (anomalie ostruttive) possono mettere a rischio la sua stessa salute. Embriologicamente derivano da difetti di formazione, canalizzazione, fusione o riassorbimento dei dotti di Muller

Surveillance of Individuals at High Risk of Developing Pancreatic Cancer:A Prevalence Meta-analysis to Estimate the Rate of Low-yield Surgery

Objective: To quantify the rate of low-yield surgery, defined as no high-grade dysplastic precursor lesions or T1N0M0 pancreatic cancer at pathology, during pancreatic cancer surveillance. Background: Global efforts have been made in pancreatic cancer surveillance to anticipate the diagnosis of pancreatic cancer at an early stage and improve survival in high-risk individuals (HRIs) with a hereditary predisposition. The negative impact of pancreatic cancer surveillance when surgery is performed for low-grade dysplasia or a non-neoplastic condition is not well quantified. Materials and Methods: A systematic search and prevalence meta-analysis was performed for studies reporting surgery with final diagnoses other than those defined by the Cancer of the Pancreas Screening (CAPS) goals from January 2000 to July 2023. The secondary outcome was the pooled proportion of final diagnoses matching the CAPS goals (PROSPERO: CRD42022300408). Results: Twenty-three articles with 5027 patients (median 109 patients/study, interquartile range 251) were included. The pooled prevalence of low-yield surgery was 2.1% (95% CI: 0.9-3.7, I 2: 83%). In the subgroup analysis, this prevalence was nonsignificantly higher in studies that only included familial pancreatic cancer subjects without known pathogenic variants, compared with those enrolling pathogenic variant carriers. No effect modifiers were found. Overall, the pooled prevalence of subjects under surveillance who had a pancreatic resection that contained target lesions was 0.8% (95% CI, 0.3-1.5, I 2: 24%]. The temporal analysis showed that the rate of low-yield surgeries decreased in the last decades and stabilized at around 1% (test for subgroup differences P&lt;0.01). Conclusions: The risk of "low-yield" surgery during pancreatic cancer surveillance is relatively low but should be thoroughly discussed with individuals under surveillance.</p

Surveillance of Individuals at High Risk of Developing Pancreatic Cancer: A Prevalence meta-analysis to Estimate the Rate of low-yield Surgery

Objective: To quantify the rate of low-yield surgery, defined as no high-grade dysplastic precursor lesions or T1N0M0 pancreatic cancer at pathology, during pancreatic cancer surveillance. Summary background data: Global efforts have been made in pancreatic cancer surveillance to anticipate the diagnosis of pancreatic cancer at an early stage and improve survival in high-risk individuals (HRI) with a hereditary predisposition. The negative impact of pancreatic cancer surveillance when surgery is performed for low-grade dysplasia or a non-neoplastic condition is not well-quantified. Methods: A systematic search and prevalence meta-analysis was performed for studies reporting surgery with final diagnoses other than those defined by the CAPS goals from January 2000 to July 2023. The secondary outcome was the pooled proportion of final diagnoses matching the CAPS goals (PROSPERO: #CRD42022300408). Results: Twenty-three articles with 5,027 patients (median 109 patients/study, IQR 251) were included. The pooled prevalence of low-yield surgery was 2.1% [95%CI 0.9-3.7], I2 83%). In the subgroup analysis, this prevalence was non-significantly higher in studies that only included familial pancreatic cancer (FPC) subjects without known pathogenic variants (PV), compared to those enrolling PV carriers. No effect modifiers were found. Overall, the pooled prevalence of subjects under surveillance who had a pancreatic resection that contained target lesions was 0.8% [95%CI 0.3-1.5], I2 24%). The temporal analysis showed that the rate of low-yield surgeries decreased in the last decades and stabilized at around 1% (test for subgroup differences P&lt;0.01). Conclusions: The risk of "low-yield" surgery during pancreatic cancer surveillance is relatively low but should be thoroughly discussed with individuals under surveillance