Publications

BACKGROUND: There is limited information regarding early development of soft-tissue and/or bone hypertrophy with facial port-wine stains (PWS). OBJECTIVE: We sought to characterize patients with hypertrophic PWS presenting during childhood. METHODS: Patients with a facial PWS and underlying hypertrophy that developed before the age of 18 years were included in a multicenter retrospective study. Age at onset of the hypertrophy, its location, association with odontologic problems, presence of other associated complications, and response to laser treatment were recorded. RESULTS: A total of 98 patients were included. The mean age at onset of hypertrophy, retrieved for 77 of 98 patients, was 5.6 years. The hypertrophy was congenital in 26%. Odontologic problems were noted in 39.8% of cases. Other complications, including cataract, asymmetric development of the maxillary bone, and speech delay/disorders, were reported in 18.4%. In all, 67 patients received laser treatment. Only 3% achieved complete or nearly complete clearance of the PWS. LIMITATIONS: As only cases of PWS with early-onset hypertrophy were included, we were unable to calculate the prevalence of this manifestation. CONCLUSION: PWS with early-onset hypertrophy are associated with a high rate of complications and a poor response to laser treatment. Periodic monitoring is recommended for early detection and treatment of complications.

Giant intracranial aneurysms are defined as greater than 25mm in diameter. They share the same surgical challenges and strategies as so-called complex aneurysms, sometimes smaller in size but presenting with similar complex anatomy. The surgical difficulties arise from the size of the sack, the presence of intraluminal thrombus, the thickness of the arterial wall, and the complexity of arterial branching on the neck. Preoperative imaging gathers complementary information from magnetic resonance imaging, computed tomographic angiography, and rotational catheter-based angiography with three-dimensional reconstruction including balloon-test occlusion. The therapeutic decision-making needs a multidisciplinary approach including endovascular, neurosurgical and anesthesiological expertises. The microsurgical treatment needs a step-by-step preoperative planning with anticipation of possible pitfalls and alternative strategies. Classical principles of aneurysm surgery have to be tailored to face the difficulties arising from the size of the sack and from the arterial wall calcifications.

Metastatic melanoma has benefited from immunotherapy and targeted therapy advances. Faced with the inescapable onset of treatment resistance, the choice of a second-line treatment can be guided by a patient-derived tumor xenograft (PDTX). This new approach requires an excellent multidisciplinary collaboration where the surgeon has a key role to play. Each patient included (stage IIIC or IV) presented with subcutaneous melanoma metastasis that could be surgically resected. The surgeon performed orthotopic PDTX on CB17-SCID mice. To validate the model, tumor material was amplified over three successive generations of animals to obtain cohorts compatible with carrying out a study to compare treatment response by targeted therapy (vemurafenib versus controls). Tumors were characterized (histologically and genetically) at all stages of the generations' amplification. Functional imaging by fluorine-18 fluorodeoxyglucose PET scan was performed for the third generation PDTX. Seventeen patients with a mutated BRAF V600E subcutaneous metastasis were included, yielding 257 PDTX. Clinical, histological, and genetic characteristics of the grafted tumors were stable over the three mice generations. The treatment response to vemurafenib was observed for all PDTX. The fluorine-18 fluorodeoxyglucose PET scan evidenced a decreased in glucose uptake in the treated tumors. PDTX models are being widely used in fundamental research and are more compatible with clinical issues. If PDTX are simple and easily reproducible in metastatic melanoma, an organized multidisciplinary platform is essential to implement them. In our experience, surgeons have a key role to play in the cohesion of this new therapeutic approach.

Melanoma is a major public health problem. In recent years, it has been shown that melanoma can be characterized by specific oncogenes mutations such as the BRAF mutation, leading to the development of new therapeutic drugs. Dabrafenib is an inhibitor of BRAF, approved as a first-line treatment of metastatic or unresectable stage 3 or 4 melanoma with the BRAF mutation. Few studies have evaluated the drug interaction potential of dabrafenib. This molecule is an enzyme inducer that increases the synthesis of drug-metabolizing enzymes, including CYP3A4, CYP2B6, CYP2C8, CYP2C9, CYP2C19, and UGT enzymes. Accordingly, the plasma concentrations of drugs metabolized by these enzymes are decreased. The decrease in plasma concentrations may cause a reduction or even loss of the clinical effect of these drugs. Many drugs metabolized by these enzymes may be affected, especially midazolam, warfarin, or rifampicin. However, interactions with immunosuppressants have not been described. Everolimus and tacrolimus are two immunosuppressive drugs metabolized by CYP3A4. We report a case of drug interaction between dabrafenib and immunosuppressive drugs (everolimus, tacrolimus), observed in a transplanted heart patient, requiring dosage adjustment of its immunosuppressive treatment to avoid graft rejection.

OBJECTIVE: Uterine infertility (UI), which can be caused by a variety of congenital or acquired factors, affects several thousand women in Europe. Uterus transplantation (UTx), at the current stage of research, offers hope for these women to be both the biological mother and the carrier of their child. However, the indications of UTx still need to be defined. The main aim of the study was to describe the different etiologies of UI and other data as marital and parental status from women requesting UTx who contacted us in the framework of a UTx clinical trial. Secondarily, we discussed the potential indications of UTx and their feasibility. STUDY DESIGN: This is an observational study. RESULTS: Of a total of 139 patients with UI, 105 patients (75.5%) had uterine agenesis, making it the leading cause of UI in this sample. Among the patients with uterine agenesis, 25% had a solitary kidney and 44.7% had undergone vaginal reconstruction. Peripartum hysterectomy, hysterectomy for cancer, and hysterectomy for benign pathologies accounted for 9.4%, 7.2% and 5% of cases, respectively. Less common causes of UI included complete androgen insensitivity syndrome (2.2% of patients) and prenatal diethylstilbestrol exposure (0.7%). Approximately 14% of the women already had at least one child and 66% were in a couple living together for at least 2 years. CONCLUSION: UTx is still under evaluation and further research is under way. Nulliparous patients with no major medical or surgical history and with normal ovarian function, who meet the legal criteria for medically assisted reproduction, represent the best indications for UTx at this stage of its development.