FOXO3a deregulation in uterine smooth muscle tumors.

OBJECTIVE: The present study aimed to investigate FOXO3a deregulation in Uterine Smooth Muscle Tumors (USMT) and its potential association with cancer development and prognosis. METHODS: The authors analyzed gene and protein expression profiles of FOXO3a in 56 uterine Leiomyosarcomas (LMS), 119 leiomyomas (comprising conventional and unusual leiomyomas), and 20 Myometrium (MM) samples. The authors used techniques such as Immunohistochemistry (IHC), FISH/CISH, and qRT-PCR for the present analyses. Additionally, the authors conducted an in-silico analysis to understand the interaction network involving FOXO3a and its correlated genes. RESULTS: This investigation revealed distinct expression patterns of the FOXO3a gene and protein, including both normal and phosphorylated forms. Expression levels were notably elevated in LMS, and Unusual Leiomyomas (ULM) compared to conventional Leiomyomas (LM) and Myometrium (MM) samples. This upregulation was significantly associated with metastasis and Overall Survival (OS) in LMS patients. Intriguingly, FOXO3a deregulation did not seem to be influenced by EGF/HER-2 signaling, as there were minimal levels of EGF and VEGF expression detected, and HER-2 and EGFR were negative in the analyzed samples. In the examination of miRNAs, the authors observed upregulation of miR-96-5p and miR-155-5p, which are known negative regulators of FOXO3a, in LMS samples. Conversely, the tumor suppressor miR-let7c-5p was downregulated. CONCLUSIONS: In summary, the outcomes of the present study suggest that the imbalance in FOXO3a within Uterine Smooth Muscle Tumors might arise from both protein phosphorylation and miRNA activity. FOXO3a could emerge as a promising therapeutic target for individuals with Unusual Leiomyomas and Leiomyosarcomas (ULM and LMS), offering novel directions for treatment strategies.

Hyperbaric oxygen therapy as adjuvant for treating wound complications after extensive resection for vulvar malignancy.

INTRODUCTION: Necrosis, wound breakdown, and infection represent major complications associated with radical vulvectomy. We aimed to analyze the feasibility of hyperbaric oxygen (HBO2) therapy as an adjunctive treatment for such complications. METHODS: We performed a retrospective analysis of the medical records, clinical charts, and operative records of vulvar cancer patients who underwent hyperbaric oxygen therapy after extensive surgical resection in our institute between 2012 and 2016, with a comparison of the clinical outcomes of patients with similar surgical procedures andsevere wound complications who did not undergo HBO2. RESULTS: A total of 16 patients were included in the study. In the subgroup treated with HBO2, seven patients were identified. Two patients had primary surgery, while five had recurrent surgery (of these, two had previously undergone radiation therapy). Six patients received reconstructive flaps (five myocutaneous and onefasciocutaneous), while one patient had primary suture. Dehiscence, ischemia and necrosis were estimated to cover 30%-80% of the surgical surface area. Surgical debridement was performed in six patients. Daily 90-minute sessions in the hyperbaric chamber were performed at a pressure of 2.2 atmospheres absolute, with partial oxygen pressure of 1672 mbar. Infection control and satisfactory healing were achieved using 10-61 sessions. All patients in the subgroup who did not receive HBO2 required surgical debridement due to partial or near-total flap necrosis, with two reconstructive interventions required. CONCLUSIONS: Hyperbaric oxygen therapy was an efficient adjuvant for wound healing and infection control in managing wound complications after extensive vulvar resections.