Nasal polyposis is defined by a Th2-driven chronic inflammation of the nose and sinus with polyps visible in the nasal fossae. It is a prevalent disease with a significant impact on the HRQL. Allergy, allergic rhinitis, asthma, and aspirin intolerance are frequently associated. The management is individual. The first line of treatment is a long-term treatment with intranasal corticosteroids. Oral corticosteroids should be used with caution. When the medical treatment fails the patient is eligible for sinus surgery. In case of symptomatic recurrence after both medical treatment and ethmoidectomy, biologics are nowadays a very promising treatment effective on all the respiratory tract. Dupilumab seems in the literature the molecule of choice. However, besides the international guidelines published by EPOS and Euforea, the molecule prescribed depends also on the availability of it in each country and the criteria edited by the health authorities to get reimbursement. Long treatment is mandatory. Traditional medical treatment is necessary as a complement to biologics.

Background: The objective of this study was to evaluate, the clinical benefit of benralizumab in patients with uncontrolled severe asthma associated with chronic rhinosinusitis with nasal polyposis (CRSwNP). Methods: The study included patients with uncontrolled severe asthma associated with CRSwNP who started therapy with benralizumab. Pulmonary function, eosinophilia, IgE, comorbidity, changes in the Asthma Control Test (ACT), Asthma Control Questionnaire (ACQ), Visual Analogue Scale (VAS), Quality of Life (AQLQ), VAS (obstruction, drip, anosmia, facial pressure), SNOT-22, decrease or withdrawal of steroids and other medication, hospital admissions and emergency visits were analysed. The FEOS scale and EXACTO were employed in the assessment of response. Results: We analyzed 58 patients who completed minimal treatment at 12 months. After treatment with benralizumab, exacerbations were reduced by 82% (p

Hereditary polyposis syndromes are rare but potentially devastating conditions which require multidisciplinary care from an early age. Societal guidelines serve as the framework for disease diagnosis, surveillance and treatment. Guidelines are based on expert opinion and ideally are evidence-based; however, recommendations may vary among different societies and can result in discordant care. This paper aims to summarize key differences in management based on societal guidelines for pediatric polyposis syndromes and identify some of the factors which may contribute to divergence in care.

Familial adenomatous polyposis (FAP) is caused by germline mutations in the tumor suppressor gene APC. To date, nearly 2000 APC mutations have been described in FAP, most of which are predicted to result in truncated protein products. Mutations leading to aberrant APC splicing have rarely been reported. Here, we characterized a novel germline heterozygous splice donor site mutation in APC exon 12 (NM_000038.5: c.1621_1626+7del) leading to exon 12 skipping in an Italian family with the attenuated FAP (AFAP) phenotype. Moreover, we performed a literature me-ta-analysis of APC splicing mutations. We found that 123 unique APC splice site mutations, in-cluding the one described here, have been reported in FAP patients, 69 of which have been char-acterized at the mRNA level. Among these, only a small proportion (9/69) results in an in-frame protein, with 4 mutations causing skipping of exon 12 and/or 13 with loss of armadillo repeat 2 (ARM2) and 3 (ARM3), and 5 mutations leading to skipping of exon 5, 7, 8, and (partially) 9 with loss of regions not encompassing known functional domains. The APC splicing mutations considered in this study cluster with the AFAP phenotype and delineate a novel molecular mechanism of pathogenesis in FAP disease.

Juvenile Polyposis Syndrome (JPS) is a rare autosomal dominant disorder characterized by multiple juvenile polyps in the gastrointestinal tract, often associated with mutations in genes such as Smad4 and BMPR1A. This study explores the impact of Smad4 knockout on the development of intestinal polyps using Collaborative Cross (CC) mice, a genetically diverse model. Our results reveal a significant increase in intestinal polyps in Smad4 knockout mice across the entire population, emphasizing the broad influence of Smad4 on polyposis. Sex-specific analyses demonstrate higher polyp counts in knockout males and females compared to their WT counterparts, with distinct correlation patterns. Line-specific effects highlight the nuanced response to Smad4 knockout, underscoring the importance of genetic variability. Multimorbidity heat maps offer insights into complex relationships between polyp counts, locations, and sizes. Heritability analysis reveals a significant genetic basis for polyp counts and sizes, while machine learning models, including k-Nearest Neighbours and Linear Regression, identify key predictors, enhancing our understanding of juvenile polyposis genetics. Overall, this study provides a comprehensive understanding of the intricate genetic interplay in the context of Smad4 knockout, offering valuable insights into potential therapeutic targets for juvenile polyposis and related diseases.

Inflammatory bowel diseases, familial adenomatous polyposis (FAP) and colorectal cancer (CRC) are associated with alterations of the intestinal microbiota. However, few data are available on the perpetuation of FAP and ulcerative colitis (UC) in relation to microbial dysbiosis. This study evaluated the UC and genetically confirmed FAP patients’ gut microbial balance in concordance to clinical outcome. Fecal materials (average mass of 0.54 g) were collected from three FAP and five UC patients to compare with healthy individuals as control group. Genomic materials of micro-biota were isolated for next generation sequencing of 16S rRNA that was performed by using QIAseq 16S/ITS panel in Illumina Miseq Platform. Data processing and bioinformatics analysis were performed via CLC Genomic Workbench bioinformatics tool. The comparison between FAP, UC and control group revealed an alteration in the intestinal microbial composition. More in details, relative abundance of class levels showed statistical significance differences among FAP, UC and control groups. Our preliminary data focused on the explanation of how dysbiosis can lead to inflammation and drive processes together with host genetic profile that leads to colorectal carcinogenesis.

Background - Compared to the da Vinci platform, there is limited experience with the Hugo RAS platform for colorectal surgery in Europe. This difference is especially notable when considering a single complex procedure, such as total colectomy. Aim - To demonstrate the feasibility and safety of using the Hugo RAS for assisted total colectomy. Clinical case- Female patient: eighteen-year-old with Familial Adenomatous Polyposis (FAP). Her IBM was 19. She underwent a total colectomy with ileorectal anastomosis using the Hugo RAS platform. The procedure took 230 minutes and had no complications. The postoperative period was uneventful. She was discharged from the hospital on the third postoperative day. Conclusion - The Hugo RAS platform is one of the emergent minimally invasive robotic platforms that can be used even in total colectomy if the proper patient selection is made. The placement choice of arms and trocars was crucial to obtain a similar operative time of the single laparoscopic approach. The certification of Hugo’s new instruments, such as energy devices and staplers, will make this platform even more competitive.