Filamin A (FLNA) is poorly expressed in adrenocortical carcinomas (ACC) compared to adenomas (ACA). Its presence is associated to a less aggressive tumour behaviour, potentially due to its role in negatively regulating IGF1R signalling. Upregulation of G2/M Wee1 kinase was shown in FLNA‐deficient mouse neural progenitor cells, and it has been reported in several tumours. This study explored Wee1 expression in ACC and its regulation by FLNA, the effects of Wee1 inhibitor AZD1775, and the impact of FLNA on its efficacy in ACC cell lines and primary cells. Analysis of FLNA and Wee1 proteins revealed elevated Wee1 and reduced FLNA in ACC compared to normal adrenal gland. FLNA knockdown increased Wee1 protein in NCI‐H295R, MUC‐1, and in primary ACC cells. Higher p‐CDK1 and cyclin B1 were shown in FLNA‐silenced MUC‐1, while decreased Wee1, p‐CDK1 and cyclin B1 resulted after FLNA overexpression. Wee1 reduction was reverted by lactacystin treatment and FLNA transfection increased p‐Wee1 (Ser123), suggesting FLNA's role in targeting Wee1 for degradation. AZD1775 dose‐dependently reduced proliferation and viability in ACC cell lines and primary cultures, and it triggered MUC‐1 cell death. Similar effects were induced by Wee1 silencing. FLNA depletion augmented AZD1775's efficacy in reducing proliferation and potentiating apoptosis in MUC‐1 and primary cells. In conclusion, we demonstrated that FLNA regulates Wee1 expression by promoting its degradation, suggesting that low FLNA typical of ACC leads to increased Wee1 with consequent cancer cells growth. It proposes Wee1 inhibition as a new potential therapeutic approach for ACC, particularly for those lacking FLNA.
Background/Objectives: The textbook outcome (TO) is a composite tool introduced to uniform surgical units and regulate surgical quality and outcomes. A patient is considered TO only if all predetermined items are met. In colorectal surgery, TO represents a new tool that can achieve important results given the prevalence of colorectal cancers. However, at present, there is a lack of uniformity in the TO’s definition. This study utilized the Delphi process to define an Italian version of the TO in colorectal cancer. Methods: The survey consisted of two rounds of online questionnaires submitted to an expert panel in colorectal oncological surgery, renowned academic surgeons, who had attended multiple scientific conferences and who were authors of papers on this specific topic. Five main topics with 26 questions were investigated through an online modified Delphi method. Items with almost 75% agreement achieved consensus. Results: Twenty-eight Italian experts were selected and participated in the two rounds. The Italian version of the textbook outcome in colorectal surgery was defined as the presence of 90-day postoperative survival, negative margins and at least 12 lymph nodes, a minimally invasive approach, ostomy fashioning if preoperatively planned, postoperative complication < Clavien–Dindo 3b, at least 10 ERAS items, no readmission, proper CHT and RT regimens, complete colonoscopy after or before surgery and Tumor Board Evaluation. Conclusions: The textbook outcome in colorectal cancer patients is a quality instrument providing a complete overview of the care of such patients, from diagnosis to treatment. We hereby propose an Italian version of the TO with outcomes chosen by an expert panel.
Background: Endoscopic onlay repair (ENDOR) approach is gaining traction as a promising technique for the treatment of diastasis recti and associated ventral hernia. However, comprehensive evidence regarding its perioperative and short-term outcomes remains scarce. The objective of this meta-analysis is to provide a comprehensive summary of the existing evidence concerning perioperative and short-term postoperative outcomes. Methods: A systematic literature review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A comprehensive search was conducted in MEDLINE, Embase, and CENTRAL until August 1st, 2024. Articles reporting outcomes of ENDOR in adult population diagnosed with diastasis recti associated or not with primary or incisional ventral hernia were included. Primary outcomes were evaluated based on safety and short-term measures, including intraoperative and short-term postoperative characteristics. A fixed effects model was used for meta-analysis. The methodological quality of the studies was assessed using the Methodological Index for Non-randomized Studies (MINORS) criteria. Results: A total of 12 studies (480 patients) were identified. Minimally invasive ENDOR resulted in an intraoperative complications and conversion rate of 1.0% [95% CI 0.0–2.0%]. The rate of seroma was 25% [95% CI 12.0–39.0%], the one of surgical site infection was 1% [95% CI 0.0–2.0%] and the rate of hematoma was 2% [95% CI 1.0–3.0%]. After a median follow-up of 16 months (1.8–39), the rate of recurrence was 2% [95% CI 0.0–3.0%]. Conclusions: The minimally invasive ENDOR approach stands out as a safe and effective method for diastasis recti and associated ventral hernia repair in selected patients, exhibiting low rates of intraoperative complications and yielding favorable outcomes. Prospero registry Registration number: CRD42024573235