Clinicopathological and molecular characterization of gastroesophageal junction (GEJ) adenocarcinoma before age of 40 years

Gastroesophageal junction (GEJ) adenocarcinoma are uncommon before age of 40 years. While certain clinical, pathological and molecular features of GEJ adenocarcinoma in older patients have been extensively studied, these characteristics in the younger population remain to be determined. In the recent literature, a high sensitivity and specificity for the detection of dysplasia and esophageal adenocarcinoma was demonstrated by using multicolor fluorescence in situ hybridization (FISH) DNA probe set specific for the locus specific regions 9p21 (p16), 20q13.2 and Y chromosome. We evaluated 663 patients with GEJ adenocarcinoma and further divided them into 2 age-groups of or= 50 years, rispectively. FISH with selected DNA probe for Y chromosome, locus 9p21 (p16), and locus 20q13.2 was investigated with formalin fixed and parassin embedded tissue from surgical resections of 17 younger and 11 older patients. Signals were counted in > 100 cells with each given histopathological category. The chromosomal aberrations were then compared in the 2 age-groups with the focus on uninvolved squamous and columnar epithelium, intestinal metaplasia (Barrett's mucosa), glandular dysplasia, and adenocarcinoma. Comparisons were performed by the X2 test, Fisher's exact test, Student's t-test and Mann-Whitney U-test as appropriate. Survival was estimated by the Kaplan-Meier method with univariate analysis by the log-rank. Significance was taken at the 5% level. There was no difference in the surgical technique applied in both age groups and most patients underwent Ivor Lewis esophagectomy. Among clinical variables there was a higher incidence of smocking history in older patient group. We identified a progressive loss of Y chromosome from benign squamos epithelium to Barrett's mucosa and glandular dysplasia, and, ultimately, to a near complete loss in adenocarcinoma in both age groups. The young group revealed significantly more losses of 9p21 in both benign and neoplastic cells when compared to the older patients group. In addition, we demonstrated an increase in the percentage of cells showing gain of locus 20q13.2 with progression from benign epithelium through dysplasia to adenocarcinoma with almost the same trend in both the young and the older patients. When compared with the older age-group, younger patients with GEJ adenocarcinoma possess similar known demographics, environmental factors, clinical, and pathologic characteristics. The most commonly detected genetic aberrations of progressive Y chromosomal loss, 9p21 locus loss, and 20q13 gains were similar in the younger and older patients. However the rate of loss of 9p21 is significantly higher in young patients, in both the benign and the neoplastic cells. The loss of 9p21, and possibly, the subsequent inactivation of p16 gene may be one of the molecular mechanisms responsible for the accelerated neoplastic process in young patients.

Framing climate change: a planetary health perspective on the pediatric age

This thesis analyzes an analysis of the risk perception of Italian paediatricians and parents regarding the impact of climate change on pediatric health. The consequences of climate change are now before our eyes; the recent pandemic has highlighted the impact that the destruction of ecosystems and global warming can have on our health. Fragile subjects will pay the most for the consequences of this crisis: children, the elderly, pregnant women. According to the World Health Organization (WHO), 88% of the disease burden linked to climate change falls on children under the age of 5. Climate change poses a challenge of equity not only between different areas of the world but also between generations: the worst consequences will weigh on those who have not caused damage to the ecosystem. This study began by studying the risk perceptions of the two main caregivers who deal with the child's health: parents and paediatricians. The study analyzed a mixed methods approach, exploiting quantitative and qualitative approaches. Two surveys were carried out in collaboration with the Italian Society of Pediatrics (SIP) and AGE, the Italian Parents' Association, using a tool already consolidated in the literature and adapted according to the needs of the thesis. Sixty semi-structured interviews were then conducted with pediatricians of different age groups and different regions of Italy. The collected data were then compared with the literature on the subject, in order to understand differences and similarities. This work is part of a still rather scarce, but growing, field of literature and represents the first study of this type in Italy.