ImportanceWhile originally approved for the management of heart failure, hypertension, and edema, spironolactone is commonly used off label in the management of acne, hidradenitis, androgenetic alopecia, and hirsutism. However, spironolactone carries an official warning from the US Food and Drug Administration regarding potential for tumorigenicity.ObjectiveTo determine the pooled occurrence of cancers, in particular breast and prostate cancers, among those who were ever treated with spironolactone.Data SourcesPubMed, Cochrane Library, Embase, and Web of Science were searched from inception through June 11, 2021. The search was restricted to studies in the English language.Study SelectionIncluded studies reported the occurrence of cancers in men and women 18 years and older who were exposed to spironolactone.Data Extraction and SynthesisTwo independent reviewers (K.B. and H.H.) selected studies, extracted data, and appraised the risk of bias using the Newcastle-Ottawa Scale. Studies were synthesized using random effects meta-analysis.Main Outcomes and MeasuresCancer occurrence, with a focus on breast and prostate cancers.ResultsSeven studies met eligibility criteria, with sample sizes ranging from 18 035 to 2.3 million and a total population of 4 528 332 individuals (mean age, 62.6-72.0 years; in the studies without stratification by sex, women accounted for 17.2%-54.4%). All studies were considered to be of low risk of bias. No statistically significant association was observed between spironolactone use and risk of breast cancer (risk ratio [RR], 1.04; 95% CI, 0.86-1.22; certainty of evidence very low). There was an association between spironolactone use and decreased risk of prostate cancer (RR, 0.79; 95% CI, 0.68-0.90; certainty of evidence very low). There was no statistically significant association between spironolactone use and risk of ovarian cancer (RR, 1.52; 95% CI, 0.84-2.20; certainty of evidence very low), bladder cancer (RR, 0.89; 95% CI, 0.71-1.07; certainty of evidence very low), kidney cancer (RR, 0.96; 95% CI, 0.85-1.07; certainty of evidence low), gastric cancer (RR, 1.02; 95% CI, 0.80-1.24; certainty of evidence low), or esophageal cancer (RR, 1.09; 95% CI, 0.91-1.27; certainty of evidence low).Conclusions and RelevanceIn this systematic review and meta-analysis, spironolactone use was not associated with a substantial increased risk of cancer and was associated with a decreased risk of prostate cancer. However, the certainty of the evidence was low and future studies are needed, including among diverse populations such as younger individuals and those with acne or hirsutism.

Background Pre-injection aspiration procedures could increase safety during soft tissue filler injections. However, various influencing factors have been detected in vitro that could result in false negative aspiration results. Objective A case series was retrospectively investigated to identify factors contributing to positive blood aspiration procedures in vivo. Methods This study evaluated 213 clinical cases positive for blood aspiration documented in an Asian population: 208 females (43.8 ± 7.2 years old) and 5 males (46.8 ± 7.8 years old) during soft tissue filler injections. Injection location, layer (depth) of injection, product injected, size of utilized needle (gauge), length of needle (inch), priming of needle (yes/no), injection angle (degree), and time until blood was visible in the needle hub (seconds) were evaluated. Results The most frequent location where a positive aspiration was observed was the pyriform fossa (n = 56; 26.3%), the most frequent plane was the supra-periosteal plane (n = 195; 91.5%), and the most frequent needle utilized was a 27G needle (n = 125; 58.7%). Statistically significantly more positive cases were identified when the needle was primed compared with an unprimed needle (P < 0.001, which was independent of the product). The estimated incidence rate was 0.04% to 0.9% for having positive aspiration procedures per total performed injection procedures. Conclusions Pre-injection aspiration could be a valuable tool to prevent accidental intravascular injection of soft tissue filler. The results of the present investigation show that aspiration can be performed with an acceptable aspiration time, that is, less than 2 seconds, if a suitable product/needle combination is chosen. Level of Evidence: 4

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Introduction: Alpha-fetoprotein (AFP) functions in utero to inhibit estrogen-mediated growth in fetal tissue. AFPep is a 9-amino acid cyclized form of the active site in AFP that impedes phosphorylation and activation of ERα. Recent studies demonstrate that AFPep inhibits estrogen-dependent growth in MCF-7 and T47D xenografts and decreases mammary tumor burden in estrogen-exposed ACI rats. It is important to identify biomarkers that predict the efficacy of AFPep. Dimerized, phosphorylated ERα (pERα) transcribes TRIM25, which is associated with breast cancer metastasis and decreased survival. KLF5 is a transcription factor downstream of pERα and is associated with breast and cervical cancer proliferation, invasiveness, and migration. We hypothesize that treatment with AFPep inhibits expression of TRIM25 and KLF5 and that these are predictive biomarkers for AFPep-mediated inhibition of estrogen-dependent growth. Methods: Expression of ERα, pERα, TRIM25, and KLF5 were assessed in three estrogen-sensitive models: immature mouse uterus, MCF7 xenografts, and canine breast tumors. Immature mice were treated with saline only, AFPep (100 μg) only, estrogen, or estrogen plus AFPep (100 μg). Twenty-four hours post treatment, uteri were removed, weighed, and blotted for biomarkers. Mice bearing MCF7 xenografts were treated with estrogen or estrogen with AFPep and biopsied after 14 days. Finally, two dogs, one with a simple tubular mammary adenoma and the other with a grade II mixed mammary carcinoma, were treated with AFPep for seven days. Results: Immature mice treated with estrogen had greater uterine-to-body weight ratio, increased ratio of pERα to total ERα, and increased KLF5 and TRIM25 expression compared to mice treated with saline alone or AFPep alone. Uteri from mice treated with estrogen and AFPep showed decreased uterine-to-body weight ratio, decreased ratio of pERα to total ERα, and decreased KLF5 and TRIM25 expression compared to uteri treated with estrogen alone. MCF7 xenografts from mice treated with estrogen and AFPep showed decreased ratio of pERα to total ERα compared to mice treated with estrogen alone. AFPep treatment of xenograft-bearing mice decreased expression of TRIM25 and KLF5 in the tumor. In the clinical canine mammary tumor study, a mixed carcinoma expressed pERα and treatment of that dog with AFPep decreased the expression of both KLF5 and TRIM25 in that tumor. A dog with a simple tubular adenoma did not express pERα, and treatment of that dog with AFPep had little impact on the expression of TRIM25 and KLF5 in the tumor. Conclusion: We conclude that AFPep inhibits estrogen-mediated growth and the ratio of pERα to total ERα. KLF5 and TRIM25 also serve as predictive markers for the efficacy of AFPep in uterus and breast tissue respectively. Citation Format: Kanthi J. Bommareddy, Anusri Kadakuntla, Michael Kuna, Priya Shivraj, Roman Ginnan, Ann Hohenhaus, James Bennett, Thomas Andersen. Trim25 and KLF5 expression predict AFPep-mediated inhibition of estrogen-dependent growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2968.