RESUMEN
OBJECTIVE: To compare pain control during vulvar biopsy after either application of 5% lidocaine-prilocaine cream or injection of 1% lidocaine. METHODS: In a single-site randomized trial, patients who needed vulvar biopsy on a non-hair-bearing surface were recruited from a gynecologic oncology clinic to compare lidocaine-prilocaine cream (placed at least 10 minutes before biopsy) with lidocaine injection (at least 1 minute prior). A sample size of 53 participants in each arm (N=106) was planned. Pain was recorded using a 100 mm visual analog scale at three time points: baseline, after application of anesthesia, and after biopsy. The primary outcome was highest pain score recorded. Secondary outcomes were pain score at biopsy, patient experience, and tolerability and acceptability. Linear regression was used to compare the primary outcome between arms while controlling for baseline vulvar pain. A convenience analysis was performed in March 2019. RESULTS: From October 2018 to March 2019, 38 patients completed informed consent and were randomized. Participants were women with median age of 60 years. Most characteristics between groups were similar. Nineteen were analyzed in the lidocaine-prilocaine group, and 18 were analyzed in the lidocaine injection group. The median highest pain score in the lidocaine-prilocaine group was 20.0 mm vs 56.5 mm in the lidocaine injection group. Controlling for baseline pain, the highest pain score in the lidocaine-prilocaine arm was 25.7 mm lower than in the lidocaine injection arm (95% CI [-45.1 to -6.3]; P<.01). Patients randomized to lidocaine-prilocaine had a significantly better experience than those receiving injected lidocaine (median experience score 2.0 mm vs 17.0 mm; P=.02). CONCLUSION: Lidocaine-prilocaine cream before vulvar biopsy resulted in a lower maximum pain score and a significantly better patient rating of the biopsy experience when compared with lidocaine injection. Lidocaine-prilocaine cream, alone, is a reasonable option to use for vulvar biopsy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03654417.
Asunto(s)
Biopsia con Aguja/métodos , Combinación Lidocaína y Prilocaína/uso terapéutico , Lidocaína/uso terapéutico , Bloqueo Nervioso/métodos , Vulva/patología , Anciano , Anestésicos Locales/uso terapéutico , Femenino , Humanos , Inyecciones , Modelos Lineales , Persona de Mediana Edad , Pomadas , Dolor/prevención & control , Manejo del Dolor , Dimensión del Dolor , Satisfacción del Paciente , Perineo , Vulva/cirugíaRESUMEN
Stimulation of cultured epithelial cells with scatter factor/hepatocyte growth factor (HGF) results in the detachment of cell-cell junctions and initiation of cell migration. Instead of coordinating collective cell behavior within a tissue, cells become solitary and have few cell-cell interactions. Since epithelial scattering is recapitulated in cancer progression and since HGF signaling drives cancer metastasis in many cases, inhibitors of HGF signaling have been proposed to act as anticancer agents. We previously sought to better understand critical components required for HGF-induced epithelial scattering by performing a forward chemical genetics screen, which resulted in the identification of compounds with no previously reported biological activity that we report here. In efforts to determine the mechanism of these compounds, we find that many compounds have broad antiproliferative effects on cancer cell lines by arrest of cell division in G2/M with minimal induction of apoptosis. This effect is reminiscent of microtubule-targeting agents, and we find that several of these scaffolds directly inhibit microtubule polymerization. Compounds are assessed for their toxicity and pharmacokinetics in vivo. The identification of novel small-molecule inhibitors of microtubule polymerization highlights the role of the microtubule cytoskeleton in HGF-induced epithelial scattering.