Hôpital Européen

Vascularized composite allotransplantation (VCA) has transformed reconstructive surgery for patients with severe tissue defects. Nonetheless, donor shortages remain a major limitation. Cross-sex VCA (CS-VCA) has been proposed as a means of expanding the donor pool, but concerns persist regarding potentially heightened rejection risks in sex-mismatched transplants. This review examines published adult CS-VCA cases up to May 2025. The primary outcomes analyzed were acute rejection episodes, allograft survival, immunological complications, and sequelae affecting form and function. Nine CS-VCA cases were identified (six upper extremity, one lower extremity, and two abdominal wall transplants). Eight involved female donors (median age, 47 years) and male recipients (median age, 30 years). Acute rejection occurred in five of nine cases; however, 11 of 13 allografts remained viable at follow-up (6-41 months) under immunosuppressive therapy. Two cases developed vascular complications, resulting in technical failure and partial amputation, respectively. Higher human leukocyte antigen (HLA) mismatches (mean, 5) were associated with complications, while fewer mismatches (mean, 3) correlated with better outcomes. In contrast to trends in solid organ transplantation, female-to-male CS-VCA demonstrated relatively favorable outcomes in the limited cases reported. These findings suggest that CS-VCA may be a feasible strategy to expand the VCA donor pool, provided that patient selection is careful, ABO/Rh and HLA compatibility are prioritized, and rigorous immunological monitoring is maintained. Further studies should investigate sex-specific immune mechanisms to optimize long-term success rates.

Orbital exenteration reconstruction remains a major reconstructive challenge because of the orbit's complex anatomy and its close relationship with the paranasal sinuses, which predispose patients to delayed healing. Traditional approaches, such as secondary intention healing or split-thickness skin grafting, may result in prolonged epithelialization and can compromise timely prosthetic rehabilitation. Acellular dermal matrices (ADM) have emerged as biological scaffolds that provide immediate coverage of the defect while preserving an open orbital cavity suitable for prosthetic fitting. A systematic review of the literature was conducted using PubMed/MEDLINE, Scopus, and Google Scholar to identify clinical studies reporting orbital exenteration reconstruction using ADM. Eligible studies included clinical series describing postoperative healing, prosthesis fitting, and complications. Ten studies encompassing 42 patients were identified, of which 4 retrospective cohort studies, including 36 patients, provided sufficient data for quantitative synthesis. Pooled analysis demonstrated a prosthesis fitting rate of 85%, with a mean time to complete re-epithelialization of ∼10 weeks. Reported complications were infrequent, including sino-orbital fistula, delayed healing, and cerebrospinal fluid leak. The use of radiotherapy did not appear to significantly affect epithelialization time or prosthetic outcomes. Overall, available evidence suggests that ADM may represent a useful adjunct for lining exenteration defects limited to the bony orbital framework, facilitating earlier epithelialization while maintaining conditions favorable for prosthetic rehabilitation. Given the rarity of orbital exenteration, the low-to-moderate quality of included studies, the heterogeneity of reconstructive strategies, and the lack of comparative studies, these findings should be considered exploratory, and larger prospective or comparative studies are needed to better define the role of ADM within the reconstructive algorithm.

Overexpression of complement genes in the tumor microenvironment, including Factor H (FH), is a strong predictor of poor prognosis in multiple cancers. Its canonical functions in the bloodborne complement cascade, though, cannot explain this prognostic impact. Here, we demonstrate that FH operates within the intracellular space in fibroblasts and tumor cells. By transcriptomics approach in patient tumors, cellular and biochemical assays we revealed that the prognostic impact of FH overexpression is mediated mainly by its cell-intrinsic functions in tumor-promoting fibroblasts and malignant cells. Intranuclear FH interacts with the cell cycle-transcription factor E2F3. FH also promotes proliferation by lowering the nuclear p53 pool. Moreover, in ccRCC cancer cells, FH also regulates cytoskeleton organization and cell morphology, potentially, via interaction with the actin capping CapZ complex. Therefore, complement FH acts as a multitasking effector, regulating cell cycle and actin polymerization, challenging the paradigm of extracellular space-restricted functioning, considered for many complement proteins.

Urothelial bladder cancer (UBC) carries significant mortality and treatment morbidity. Conventional diagnostic and monitoring methods, including cystoscopy and biopsy, are invasive and limited in sensitivity. Circulating tumor DNA (ctDNA), a minimally-invasive "liquid biopsy," has emerged as a promising tool for real-time disease assessment. This study aimed to systematically evaluate the diagnostic, prognostic, and predictive value of plasma and urine ctDNA in localized, locally advanced, and metastatic UBC. A systematic review was conducted according to PRISMA guidelines using PubMed, MEDLINE, and Web of Science databases (January 2016-October 2025). Eligible studies evaluated plasma and urine ctDNA. Main outcomes included diagnostic performance, correlation with tissue mutations, disease monitoring, and prognostic or predictive value. Data synthesis focused on ctDNA detection methods, timing relative to treatment, and survival outcomes. KEY FINDINGS AND LIMITATIONS: ctDNA showed strong concordance with tumor tissue mutations and high potential for real-time monitoring of tumor burden. Data are more robust in muscle-invasive bladder cancer (MIBC) than non-muscle-invasive bladder cancer (NMIBC). Postcystectomy ctDNA positivity was an independent predictor of recurrence-free, progression-free, and overall survival. ctDNA clearance correlated with response to neoadjuvant chemotherapy and immune checkpoint inhibitors. In metastatic disease, high ctDNA mutation burden was associated with shorter overall survival and resistance mechanisms, such as PIK3CA-mediated fibroblast growth factor receptor inhibitor resistance. Limitations included heterogeneous methodologies, variable assay sensitivity, and small patient cohorts. ctDNA represents a powerful non-invasive biomarker for diagnosis, surveillance, and treatment guidance in UBC. Ongoing phase III trials (IMvigor011, TOMBOLA, MODERN) may establish its clinical utility as a standard tool for personalized disease management.

Ferroptosis is an oxidative, lipid peroxidation-driven form of regulated cell death that occurs when antioxidant and organelle-protective systems are compromised. Increasing evidence implicates ferroptosis as a process that can exert both tumour-suppressive and tumour-promoting effects depending on cellular context at multiple stages of cancer evolution (from tumour initiation to metastatic colonization), sparking substantial interest in therapeutically exploiting this mechanism of cell death. Yet, despite rapid preclinical progress, clinical translation of ferroptosis-based strategies remains nascent. In this Review, we examine the major barriers to translation, including pharmacological limitations, tumour-intrinsic heterogeneity, microenvironmental and immune constraints, and gaps in current preclinical modelling. We also highlight emerging opportunities such as new ferroptosis-inducing agents, biomarker-guided patient selection and rational combinations with chemotherapy, radiotherapy, targeted agents or immunotherapies. Finally, we outline a translational roadmap for integrating ferroptosis-based therapies into oncology practice. By defining key challenges and future directions, this Review aims to position ferroptosis as a viable therapeutic paradigm and to accelerate progress towards clinical application.