Clinical outcomes with utilization of high-potency topical steroids in patients with lichen sclerosus-associated vulvar cancer.

OBJECTIVES: To evaluate the impact of high-potency topical steroid use on risk of recurrence of lichen sclerosus-associated vulvar cancer. METHODS: This is a retrospective cohort study evaluating patients with lichen sclerosus (LS)- associated vulvar squamous cell cancer (VSCC). Demographic and clinical outcome data were compared between two comparison groups: patients who received steroids, mainly clobetasol, and patients who did not receive steroids following treatment of LS-related vulvar cancer. Categorical variables were compared using Fisher's exact test or chi-square test. Continuous variables were compared using a two-sided student's t-test. Time to recurrence (TTR) and overall survival (OS) were analyzed using Kaplan-Meier survival plot and compared using Mantel-Cox log rank test. Cox proportional hazard regression models were conducted to generate hazard ratios for both TTR and OS. A p value of <0.05 was considered statistically significant. RESULTS: A total of 49 patients were included, with 36 patients receiving steroid treatment and 13 patients in the expectant management group. The median age of diagnosis was 68. The average BMI was 31.7 +/- 7.0. The median length of follow up was 41 months. The majority of patients were diagnosed with stage I VSCC. There was no difference in demographics or oncologic management of vulvar cancer between the two cohorts. Overall recurrence was decreased among patients who received steroid treatment when compared to patients who did not, 12 patients (33.3%) versus 9 patients (69.2%) respectively (p = 0.048). CONCLUSIONS: High-potency topical steroid use following treatment of lichen sclerosus-associated vulvar squamous cell carcinoma is associated with decreased risk of recurrence and prolonged median time to recurrence.

Clinical factors associated with failed sentinel lymph node mapping in endometrial cancer.

Objective: Sentinel lymph node (SLN) mapping is a highly accurate surgical technique for detecting metastases in endometrial cancer. The objective of this study was to identify clinical factors associated with failed mapping. Methods: All patients with endometrial cancer undergoing minimally-invasive staging and planned SLN biopsy from 1/1/2017 to 12/31/2020 at a single institution were identified retrospectively. Demographic, clinicopathologic and treatment data were obtained. Data were compared using descriptive statistics. Univariate and multivariable logistic regression were performed to identify predictors of failed mapping. Results: 819 patients were identified with a mean age of 64.6 years (range 26-93) and mean BMI of 35.6 kg/m2 (range 18-68). Most (88.5 %, 725/819) had early-stage disease and endometrioid histology (82.3 %, 674/819). A majority (74.2 %, 608/819) had successful bilateral mapping, and 54 (6.6 %) had unsuccessful bilateral mapping. Increasing BMI was significantly associated with unsuccessful bilateral mapping: patients with BMI > 30 were more likely to have unsuccessful SLN mapping (p = 0.033). Among patients with known lymph node status (799/819), patients with macrometastases and micrometastases were more likely to have failed bilateral mapping compared to those with negative SLNs or isolated tumor cells (p = 0.013). On multivariable analysis, higher BMI and histology were associated with failed bilateral mapping (OR = 1.023, 95 % CI (1.005, 1.041) and OR = 1.678, 95 % CI (1.177, 2.394), respectively). Conclusion: SLN mapping has a high success in patients undergoing minimally-invasive surgical staging for endometrial cancer. Increasing BMI, high risk histology, and lymph node metastases are risk factors for failed mapping.

Same-day Hospital Discharge after Minimally Invasive Hysterectomy in a Gynecologic Oncology Practice: Feasibility, Safety, Predictors of Admission, and Adverse Outcomes.

STUDY OBJECTIVES: (1) Determine the feasibility and safety of same-day hospital discharge (SDHD) after minimally invasive hysterectomy (MIH) in a gynecologic oncology practice and (2) detail predictors of immediate postoperative hospital admission and multiple 30-day adverse outcomes. DESIGN: Retrospective cohort study. SETTING: University of Pittsburgh Medical Center Magee-Womens Hospital. PATIENTS: MIH by a gynecologic oncologist between January 2017 and July 2019. INTERVENTIONS: Clinicopathologic, operative, and medical characteristics, as well as 30-day postoperative complications, emergency department (ED) encounters, and hospital readmissions were extracted. Admitted and SDHD patients were compared using descriptive, chi-square, Fisher's exact, t test, and logistic regression analyses. Univariate and multivariable analyses (MVA) revealed predictors of postoperative hospital admission, 30-day readmission, and a 30-day composite adverse event variable (all-reported postoperative complications, ED encounter, and/or readmission). MEASUREMENTS AND MAIN RESULTS: A total of 1124 patients were identified, of which 77.3% had cancer or precancer; 775 patients (69.0%) underwent SDHD. On MVA, predictors of postoperative admission included older age, distance from hospital, longer procedure length, operative complications, start time after 2 PM, radical hysterectomy, minilaparotomy, adhesiolysis, cardiac disease, cerebrovascular disease, venous thromboembolism, diabetes, and neurologic disorders (p <.05). Moreover, 30-day adverse outcomes were rare (complication 8.7% National Surgical Quality Improvement Program/11.9% all-reported; ED encounter 5.0%; readmission 3.6%). SDHD patients had fewer all-reported complications (10.3% vs 15.5%, p = .01), no difference in ED encounters (4.6% vs 5.7%, p = .44), and fewer observed readmissions (2.8% vs 5.2%, p = .05). Predictors of readmission were identified on univariate; MVA was not feasible given the low number of events. Longer procedure length and cardiac and obstructive pulmonary disease were predictors of the composite adverse event variable (p <.05). CONCLUSION: SDHD is feasible and safe after MIH within a representative gynecologic oncology practice. Clinicopathologic, medical, and surgical predictors of multiple adverse outcomes were comprehensively described. By identifying patients at high risk of postoperative adverse events, we can direct SDHD selection in the absence of standardized institutional and/or national consensus guidelines and identify patients for prehabilitation and increased perioperative support.

Novel Therapies in Gynecologic Cancer.

During the past decade, considerable strides have been made in the understanding and treatment of gynecologic cancers. The advent of PARP inhibitors, antiangiogenic therapies, immunotherapy combinations, and targeted agents have altered the standard of care in ovarian, endometrial, and cervical cancers. However, continued advancement in the treatment of gynecologic cancers is critical. Fortunately, exciting work defining new therapeutic targets and novel treatment strategies is on the horizon. Here, we discuss emerging treatments for gynecologic cancers, including endometrial, cervical, ovarian, and rare gynecologic cancers. We highlight research that has deepened our understanding of the unique biology and molecular underpinnings of these cancers and is being translated into powerful new treatment approaches. We particularly highlight the advent of immunotherapy in endometrial cancer; radiosensitizers in cervical, vaginal, and vulvar cancers; targeted therapies in ovarian cancer; and molecularly driven approaches to treat rare gynecologic cancers. Continued basic, translational, and clinical research holds the promise to change the landscape of gynecologic cancer and improve the lives of all women impacted by these diseases.

An Orthotopic Mouse Model of Ovarian Cancer using Human Stroma to Promote Metastasis.

Ovarian cancer is characterized by early, diffuse metastasis with 70% of women having metastatic disease at the time of diagnosis. While elegant transgenic mouse models of ovarian cancer exist, these mice are expensive and take a long time to develop tumors. Intraperitoneal injection xenograft models lack human stroma and do not accurately model ovarian cancer metastasis. Even patient derived xenografts (PDX) do not fully recapitulate the human stromal microenvironment as serial PDX passages demonstrate significant loss of human stroma. The ability to easily model human ovarian cancer within a physiologically relevant stromal microenvironment is an unmet need. Here, the protocol presents an orthotopic ovarian cancer mouse model using human ovarian cancer cells combined with patient-derived carcinoma-associated mesenchymal stem cells (CA-MSCs). CA-MSCs are stromal progenitor cells, which drive the formation of the stromal microenvironment and support ovarian cancer growth and metastasis. This model develops early and diffuses metastasis mimicking clinical presentation. In this model, luciferase expressing ovarian cancer cells are mixed in a 1:1 ratio with CA-MSCs and injected into the ovarian bursa of NSG mice. Tumor growth and metastasis are followed serially over time using bioluminescence imaging. The resulting tumors grow aggressively and form abdominal metastases by 14 days post injection. Mice experienced significant decreases in body weight as a marker of systemic illness and increased disease burden. By day 30 post injection, mice met endpoint criteria of >10% body weight loss and necropsy confirmed intra-abdominal metastasis in 100% of mice and 60%-80% lung and parenchymal liver metastasis. Collectively, orthotopic engraftment of ovarian cancer cells and stroma cells generates tumors that closely mimic the early and diffuse metastatic behavior of human ovarian cancer. Furthermore, this model provides a tool to study the role of ovarian cancer cell: stroma cell interactions in metastatic progression.

Smooth Muscle Cells in Pelvic Washings at Time of Benign Hysterectomy.

STUDY OBJECTIVE: To evaluate if smooth muscle cells can be detected in pelvic washings at the time of intact hysterectomy. DESIGN: A multicentered pilot cohort study (Canadian Task Force classification II-2). SETTING: Two academically affiliated tertiary referral centers. PATIENTS: Patients undergoing total hysterectomy for benign indications without morcellation by minimally invasive gynecologic surgeons were enrolled from January 2018 to July 2018. INTERVENTIONS: Pelvic washings were collected at 2 times during surgery: after abdominal entry and after vaginal cuff closure. Cell blocks were generated, and slides were stained using hematoxylin and eosin, smooth muscle actin, and desmin and interpreted by 1 expert pathologist at each institution. MEASUREMENTS AND MAIN RESULTS: Thirty-eight subjects were recruited; 3 subjects were excluded because of unplanned morcellation. Smooth muscle uterine cells were detected in 1 prewash specimen and 2 postwash specimens. The group with positive washings was noted to have longer procedure times (136 vs 114 minutes), lower blood loss (25 vs 86 mL), and higher uterine weight (242 vs 234 g) compared with negative washings group. CONCLUSION: Tissue dissemination of uterine cells may be possible at the time of hysterectomy. Larger prospective studies are needed to better describe the incidence of and risk factors for tissue dissemination.

Sebaceous carcinoma arising within an ovarian mature cystic teratoma: A case report with discussion of clinical management and genetic evaluation.

Sebaceous carcinomas are rare tumors, with the majority of described cases occurring within the eyelid. To date, there are nine documented reports of sebaceous carcinoma arising within a mature cystic teratoma of the ovary. Although the majority of cases originate from idiopathic mutations, there exists a strong association between this rare tumor and hereditary syndromes of DNA mismatch repair deficiency, such as Lynch syndrome and the lesser-known Muir-Torre syndrome. Here we present the case of a 67 year-old woman with a longstanding history of a small left ovarian cyst with sonographic features of an ovarian dermoid. After nine years, the left adnexal mass was noted to have enlarged, and she underwent a laparoscopic bilateral salpingo-oophorectomy. The final pathology was reported as sebaceous carcinoma arising within a mature cystic teratoma. The patient underwent subsequent surgical staging and has been followed for eight months without evidence of disease. This report includes a review of the current literature, as well as a brief discussion of the clinical management of women with sebaceous carcinoma arising within a mature teratoma. Additionally, we comment on the broader, hereditary significance of a diagnosis of sebaceous carcinoma, and use this case to demonstrate the thorough histologic and genetic evaluation that is recommended for patients diagnosed with this rare tumor.

Aspirin use correlates with survival in women with clear cell ovarian cancer.

Data from colon, breast and prostate cancers suggest that aspirin users have reduced mortality. While the direct mechanism remains uncertain, aspirin can suppress the COX-dependent and independent pathways involved in tumor progression. We hypothesized that aspirin users with clear cell ovarian cancer would have improved survival outcomes. We performed a retrospective review of patients with clear cell ovarian cancer diagnosed between 1995 and 2010, and followed outcomes through 2016. Patients underwent primary cytoreductive surgery followed by platinum-based chemotherapy. Aspirin use was defined by medication documentation in two records more than six months apart. Statistical tests included Fisher's exact, Kaplan-Meier and Cox regression analyses. Seventy-seven patients met inclusion criteria. Fifty-four patients (70%) had stage I-II disease. Thirteen patients (17%) used aspirin. Aspirin users had a statistically longer disease-free survival compared to non-users (HR 0.13, p = .018). While median disease-free survival was not reached for either group, 1 of 13 (8%) aspirin users recurred at 24 months, compared to 18 of 64 (28%) non-users. Aspirin users demonstrated longer overall survival (HR 0.13, p = .015). Median survival was not reached for aspirin users, compared to 166 months for non-users. Aspirin use retained significance (HR 0.13, p = .044) after controlling for age, stage and cytoreductive status. In this small cohort of women with clear cell ovarian cancer, aspirin use correlated with improved disease-free and overall survival, and retained independent significance as a positive prognostic factor. Further research is warranted to confirm these findings before considering aspirin as a therapeutic intervention.

Nestin expression and in vivo proliferative potential of tanycytes and ependymal cells lining the walls of the third ventricle in the adult rat brain.

There is a disagreement in the literature concerning the degree of proliferation of cells in the walls of the third ventricle (3rdV) under normal conditions in the adult mammalian brain. To address this issue, we mapped the cells expressing the neural stem/progenitor cell marker nestin along the entire rostrocaudal extent of the 3rdV in adult male rats and observed a complex distribution. Abundant nestin was present in tanycyte cell bodies and processes and also was observed in patches of ependymal cells as well as in isolated ependymal cells throughout the walls of the 3rdV. However, we observed very limited ependymal cell or tanycyte proliferation in normal adult rats as determined by bromodeoxyuridine (BrdU) incorporation or the expression of Ki-67. Moreover, fewer than 13% of the cells that were BrdU-positive (BrdU+) or Ki-67-positive (Ki-67+) expressed nestin. These observations stand in contrast to those made in the subventricular zone of the lateral ventricle (SVZ) and subgranular zone of the hippocampal formation (SGZ), where cell proliferation measured by BrdU incorporation or Ki-67 expression is observed frequently in cells that also express nestin. Thus, while ependymal cell or tanycyte cell proliferation can be promoted by the addition of mitogens, dietary modifications or other in vivo manipulations, the proliferation of ependymal cells and tanycytes in the walls of the 3rdV is very limited in the normal adult male rat brain.