Antineoplastic Drug Synergy of Artesunate with Navitoclax in Models of High-Grade Serous Ovarian Cancer.

Artesunate belongs to a class of medications derived from the sweet wormwood plant (Artemisia annua) known as artemisinins. Artesunate has traditionally been used as a frontline treatment for severe malaria but has also demonstrated antineoplastic activity against various malignancies, including ovarian cancer. Data suggest that artesunate exacerbates cellular oxidative stress, triggering apoptosis. In the current study, we investigated the ability of navitoclax, an inhibitor of the antiapoptotic Bcl-2 protein family, to enhance artesunate efficacy in ovarian cancer cells. Artesunate and navitoclax both demonstrated antiproliferative effects on 2D and 3D ovarian cancer cell models as single agents. Upon combination of navitoclax with artesunate, antineoplastic drug synergy was also observed in each of the 2D cell lines and ovarian tumor organoid models tested. Further investigation of this drug combination using intraperitoneal CAOV3 xenograft models in BALB/scid mice showed that the artesunate/navitoclax doublet was superior to single-agent artesunate and vehicle control treatment. However, it did not outperform single-agent navitoclax. With optimization, this drug combination could provide a new therapeutic option for ovarian cancer and warrants further preclinical investigation.

Enhanced Recovery after Surgery Protocol to Improve Racial and Ethnic Disparities in Postcesarean Pain Management.

OBJECTIVE: The objective of this study was to assess the efficacy of an enhanced recovery after surgery (ERAS) protocol and determine its effect on racial/ethnic disparities in postcesarean pain management. STUDY DESIGN: We performed an institutional review board-approved retrospective cohort study of scheduled cesarean deliveries before and after ERAS implementation at a single urban academic institution. Pre-ERAS, all analgesic medications were given postoperatively on patient request. The ERAS protocol included preoperative acetaminophen and celecoxib. Postoperatively, patients received scheduled nonsteroidal anti-inflammatory drugs and acetaminophen. Oral oxycodone was available as needed, and opioid patient-controlled analgesia was eliminated from the standard order set. The primary outcome was total opioid use in the first 48 hours after cesarean, pre- and post-ERAS, reported in total milliequivalents of intravenous morphine (MME). A secondary analysis of opioid use and pain scores by racial groups was also performed. Chi-square, independent t-tests, analysis of variance, Mann-Whitney U, and Kruskal-Wallis tests were used depending on variable and data normality. RESULTS: Pre-ERAS and post-ERAS groups included 100 women each. Post-ERAS, total opioid use in 48 hours was less (40.8 vs. 8.6 MME, p < 0.001) and visual analog scale (VAS) pain scores were lower on postoperative day 1 (POD1) and 2 (POD2) (POD1 maximum at rest: 6.7 vs. 5.3, p < 0.001). Pre-ERAS pain scores differed by race with non-Hispanic Black (NHB) patients reporting the highest mean and max VAS pain scores POD1 and POD2 (POD1, maximum VAS at rest: NHB-7.4, non-Hispanic White-6.6, Hispanic-5.8, Asian-4.4, p = 0.006). Post-ERAS, there were no differences in postoperative pain scores between groups with movement on POD1 and POD2. CONCLUSION: A standardized ERAS protocol for postcesarean pain decreases opioid use and may improve some racial disparities in postcesarean pain control. KEY POINTS: · ERAS protocols improve postoperative pain control and lower postoperative opioid use.. · Studies show that there are racial and ethnic disparities in postpartum pain control.. · Protocols standardize care and may decrease the effects of provider implicit bias..

Clinical Characteristics and Histologic Features of Hysterectomy Specimens From Transmasculine Individuals.

OBJECTIVE: To describe the clinical characteristics of transmasculine individuals who underwent hysterectomy and characterize surgical pathology findings. METHODS: Under an institutional review board-approved protocol, transmasculine individuals who were undergoing hysterectomy and bilateral salpingectomy or bilateral salpingo-oophorectomy were retrospectively identified from a single institution. Past medical, surgical, obstetric, and gynecologic history were collected, including prior testosterone use, cervical cancer screening status, and preoperative pelvic imaging. Surgical pathologic findings of the endometrium, ovaries, and cervix were collected. RESULTS: A total of 72 individuals were included. The median age was 30 years (range 19-51). The majority of patients had private insurance (n=53, 74%) and were on testosterone at time of the preoperative visit (n=63, 88%). Forty-two patients (58%) reported anxiety, depression, or bipolar disorder, and 34 patients (47%) were taking an antidepressant or mood stabilizer. Of the 68 patients eligible for cervical cancer screening, 33 (49%) were up to date before their surgical consultation visits. Pelvic pain was the leading indication for surgery (n=65, 90%), and 29 patients (40%) had multiple listed indications for surgery. Surgical pathology results included cervical intraepithelial neoplasia 2-3 in three patients (4%), endometrial or cervical atrophy in 13 patients (18%), and ovarian or paratubal cysts in 16 patients (22%). CONCLUSION: This study describes the distinct clinical characteristics and surgical pathology findings that health care professionals should consider when caring for this unique patient population, including a relatively high rate of mental health conditions, pelvic pain as the leading indication for surgery, and the presence of endometrial or cervical atrophy and ovarian or paratubal cysts on surgical pathology.

Collaborative Efforts Between Interventional Radiology and Obstetrics/Gynecology.

Since the introduction of uterine artery embolization as a treatment option for symptomatic leiomyomas, there has been a growing interest in expanding the role of interventional radiology (IR) in the evaluation and treatment of obstetrics and gynecology (OBGYN) patients. This review provides an overview of opportunities for collaboration between IR and OBGYN. This can include medically and/or surgically complex patients, efforts to reduce quantitative blood loss, obstetrical emergencies, and consideration of fertility or uterine preservation. Increased collaborative efforts between IR and OBGYN would allow for patients to be fully informed regarding the complete spectrum of surgical and nonsurgical treatment options available to them. The purpose of this review is to foster opportunities to improve outcomes and respect patient values.

Digital Quantification of Ki-67 and PHH3 in the Classification of Uterine Smooth Muscle Tumors.

Uterine smooth muscle tumors are the most common tumors of the female genital tract and include leiomyoma (LM) and its variants, smooth muscle tumors of uncertain malignant potential (STUMP), and leiomyosarcoma (LMS). Accurate diagnosis of LMS is determined by nuclear atypia, mitotic count, and the presence or absence of tumor cell necrosis, a process which is often difficult and subjective. In this study, we correlated digital quantification of proliferation marker Ki-67 and mitotic marker phosphohistone H3 (PHH3) to mitotic count, classification of uterine smooth muscle tumors, and clinical outcomes. A total of 39 cases (17 LMS, 5 STUMP, 10 LM with bizarre nuclei, and 7 LM) were included. Mitotic count, Ki-67, and PHH3 were significantly correlated. When comparing the LMS group to the STUMP, LM with bizarre nuclei, and LM groups combined, LMS showed a significantly greater digital quantification of Ki-67 (median 10.6% vs. 0.4%, P<0.001) and PHH3 (median 0.5% vs. 0.14%, P=0.022). Ki-67 was a better predictor of LMS compared with PHH3 (area under the curve 0.92 vs. 0.73, P=0.017). Above a threshold Ki-67 value of 3.8%, the sensitivity was 82% and specificity was 91%. Clinical outcomes were available for 10 patients (8 LMS and 2 STUMP), and inferior progression-free survival was noted for patients with higher Ki-67 values. Overall, this study suggests that digital quantification of Ki-67 can potentially aid in diagnosis of LMS.

Stereotactic body radiation therapy for oligometastatic gynecologic malignancies: A systematic review.

OBJECTIVE: To assess the efficacy and safety of stereotactic body radiation therapy (SBRT) for oligometastatic gynecologic malignancies. METHOD: A comprehensive search of the PubMed, Medline, and EMBASE databases was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. "Oligometastatic" was defined as a limited number of uncontrolled/untreated metastatic lesions (typically ≤ 5), including regional nodal metastases. Primary outcomes were response rate (complete response or partial response), local control of oligometastatic lesions, and toxicity. RESULTS: Of 716 screened records, 17 studies (13 full length articles, 4 conference abstracts) were selected and analyzed as 16 unique studies. A total of 667 patients were treated with ~1071 metastatic lesions identified. Primary sites included ovarian (57.6%), cervical (27.1%), uterine (11.1%), vaginal (0.4%), vulvar (0.3%), and other/unspecified (3.4%). Most patients (65.4%) presented with a single metastatic lesion. Metastatic lesion sites included the abdomen (44.2%), pelvis (18.8%), thorax (15.5%), neck (4.6%), central nervous system (4.3%), bone (1.6%), and other/unspecified (11%). Of the lesions, 64% were nodal. Response rate (among 8 studies) ranged from 49% to 97%, with 7/8 studies reporting > 75% response rate. Local control ranged from 71% to 100%, with 14/16 studies reporting ≥ 80% local control. No grade ≥ 3 toxicities were observed in 9/16 (56%) studies. Median progression-free survival (PFS) (among 10 studies) ranged from 3.3 months to 21.7 months. Disease progression most commonly occurred outside of the SBRT radiation field (79% to 100% of failures). CONCLUSIONS: SBRT for oligometastatic gynecologic malignancies is associated with favorable response and local control rates but a high rate of out-of-field progression and heterogeneous PFS. Additional study into rational combinations of SBRT and systemic therapy appears warranted to further improve patient outcomes.

A Discussion of High-Risk HPV in a 6-Year-Old Female Survivor of Child Sexual Abuse.

BACKGROUND: Human papilloma viruses (HPVs) cause a variety of clinical manifestations in children including skin warts, laryngeal papillomas, and condyloma acuminatum. Whereas the mode of transmission is well understood and management of HPV infection is clearly defined by guidelines in adults, less is known about the mode of transmission, natural history of disease, and appropriate management of high-risk anogenital HPV infections in children. CASE: The patient is a previously healthy 6-year-old female who presented with multiple vaginal lesions causing pain and discomfort and was diagnosed with HPV 18 positive CIN I. SUMMARY AND CONCLUSION: Children infected with high-risk HPV subtypes remain a vulnerable patient population, and there is minimal literature on the natural history of disease and effects of overtreatment. Based on a literature review, conservative management, HPV vaccination, and consideration of the cervical cancer screening guidelines for adolescent females are an appropriate treatment course until more studies are reported on cervical cancer screening in survivors of child sexual abuse.