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Introduction: Artificial tear substitutes are key elements in the first-line treatment of dry eye disease (DED). We hypothesized that GlicoPro ® , a new multimolecular complex based on proteins, sulfured and unsulfured glycosaminoglycans and opiorphin, was able to significantly improve the effect of hydroxypropyl-methylcellulose (HPMC) eyedrops in treating DED., Methods: We performed an in vitro experiment and a clinical study, comparing an HPMC + GlicoPro ® -based to an HPMC-based ophthalmic formulation (similar kinematic viscosity and comparable HPMC concentration). An in vitro dry eye model was established by inducing hyperosmolarity in the base medium of human corneal epithelial cells HCE-2. After treatment with ophthalmic formulations, the expression levels of inflammatory cytokines and enzymes (IL-20, IL-1β, TNF-α, IL-6, IL-8, MMP-9, and MCP-1) was measured by real-time polymerase chain reaction. Moreover, we performed a single-blind randomized 1:1 clinical trial, aimed to compare the efficacy of the two formulations instilled four times per day (QID), in treating mild-to-moderate DED. Symptoms (Ocular Surface Disease Index and Symptom Assessment iN Dry Eye), clinical signs, and ocular surface imaging data were assessed at baseline and after 1 and 3 months of treatment., Results: In vitro experiment: under hyperosmotic conditions, corneal epithelial cells upregulated the expression of inflammatory cytokines IL-20, IL-1β, TNF-α, IL-6, and IL-8. Treatment with HPMC + GlicoPro ® significantly decreased the expression of all inflammatory markers tested, including cytokines, MMP-9, and MCP-1 (P < 0.05)., Clinical Study: the HPMC + GlicoPro ® formulation showed a significantly higher effect in improving symptoms (overall treatment effect: P < 0.001), tear film stability, and markers of inflammation on corneal confocal microscopy (P < 0.01)., Conclusions: Both in vitro and clinical data provided evidence supporting the role of GlicoPro ® in improving the effect of HPMC in DED treatment., Clinical Trial Registration: NCT06726525., Competing Interests: Declarations. Conflict of Interest: Edoardo Villani has received honoraria from AbbVie, Alcon, Diadema, FB Vision, Fidia, Essilor Luxottica, NTC, Santen, Sifi, Thea, Unifarco, Visufarma for contributing to advisory boards, educational events, and/or expert panels. Pasquale Aragona has received honoraria from AbbVie, Alcon, Bausch and Lomb, DMG, FB Vision, Fidia, Medivis, Santen, Sifi, Sun Pharma, Thea for contributing to advisory boards, educational events, and/or expert panels. Giuseppe Campagna, Valentina Gentili, Elisa Imelde Postorino, Paola Genovese, Paola Palino, Gloria Maini, Alice Carbucicchio, Eleonora Ferioli, Paolo Nucci, and Roberta Rizzo declare that they have no competing interests. Ethical Approval: The clinical study was approved by Intercompany Ethics Committee of Messina (Italy), protocol number: Prot. 20–22, and was performed in accordance with the Helsinki Declaration of 1964 and its later amendments. All subjects included provided informed consent to participate in the study., (© 2025. The Author(s).)

Dedifferentiated endometrioid adenocarcinoma is characterised by the coexistence of an undifferentiated carcinoma and a low-grade endometrioid adenocarcinoma. The low-grade component in this subtype of endometrial carcinoma is Grade 1 or 2 according to the Federation of Gynaecology and Obstetrics (FIGO) grading system. The coexistence of low-grade endometrial carcinoma and solid undifferentiated carcinoma can cause diagnostic problems on histological examination. In fact, this combination can often be mistaken for a more common Grade 2 or Grade 3 endometrial carcinoma. Therefore, this subtype of uterine carcinoma can often go under-recognised. An accurate diagnosis of dedifferentiated endometrial carcinoma is mandatory because of its poorer prognosis compared to Grade 3 endometrial carcinoma, with a solid undifferentiated component that can amount to as much as 20% of the entire tumour. The aim of this review is to provide clinical, immunohistochemical, and molecular data to aid with making an accurate histological diagnosis and to establish whether there are any findings which could have an impact on the prognosis or therapeutic implications of this rare and aggressive uterine neoplasm.

Background: Early colorectal cancer (ECC) is defined as T1NXM0 colorectal cancer (CRC). Although a non-negligible number of T1-CRCs presents metastatic lymph-nodes, local excision is increasingly proposed as alternative to radical resection. Several criteria have been suggested to identify low-risk T1-CRC, but recommendations on this topic are still heterogeneous. This study aims to identify criteria associated with N+ T1-CRC, to select patients to undergo (or not) local excision., Methods: A retrospective analysis of demographic, clinical, and histology criteria of 122 consecutive T1-CRC patients undergoing radical resection at Parma University Hospital between 2000 and 2018 has been performed., Results: Lymph-node metastasis (LNM) was observed in 15/122 patients (12.3%). No LNM was observed among well-differentiated (G1) tumors (0/37), while 10/65 (15.4%) G2 cases as well as 5/20 (25%) G3 patients presented LNM. G1 was associated with absence of LNM (p = 0.013). After excluding G1 patients, the rate of N + T1-CRC was 17.6% (15/85). LNM was observed in 4/8 (50%) patients with lymphovascular invasion (LVI) and in 11/77 (14.2%) without LVI. LVI resulted being associated with LNM (p < 0.042). LNM was reported in 28.3% of cases with a tumor infiltration >4.25 mm (13/46), compared to 5.1% in cases with an infiltration ≤4.25 mm (2/39) (p = 0.012). In Cox regression analysis, the higher hazard ratio (HR) was reported for the LVI + and infiltration >4.25 mm (HR 24.849)., Conclusions: In patients with ECC (pT1NXM0), good differentiation (G1), absence of lymphovascular invasion (LVI-), and tumor radial infiltration ≤4.25 mm may allow performing local resection and avoiding radical surgery., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Mesothelin (MSLN) is a protein expressed in the mesothelial cell lining of the pleura, peritoneum, and pericardium; its biological functions in normal cells are still unknown. Experimental studies using knockout mice have suggested that this molecule does not play an important role in development and reproduction. In contrast, it has been observed that this molecule is produced in abnormal amounts in several malignant neoplasms, such as mesotheliomas and pancreatic adenocarcinomas. Many molecular studies have also demonstrated that mesothelin is overexpressed in HSOCs. Here, we discuss the current knowledge of mesothelin and focus on its role in clinical and pathological diagnoses, as well as its impact on the prognosis of HSOC. Moreover, regarding the binding of MSLN to the ovarian cancer antigen CA125, which has been demonstrated in many studies, we also report on signal transduction pathways that may play an important role in the spread and neoplastic progression of this lethal neoplasm. Given that mesothelin is overexpressed in many solid tumours and has antigenic properties, this molecule could be considered an antigenic target for the treatment of many malignancies. Consequently, we also review the literature to report on mesothelin-targeting therapies for HSOC that have been recently investigated in many clinical studies.