Adherence to risk-reducing salpingo-oophorectomy guidelines among gynecologic oncologists compared to general gynecologists.

BACKGROUND: Risk-reducing bilateral salpingo-oophorectomy reduces mortality from high-grade serous carcinoma in patients with hereditary breast and ovarian cancer associated gene mutations. Ideal surgical management includes 5 steps outlined in 2005 by the Society of Gynecologic Oncology and the American College of Obstetricians and Gynecologists. In addition, it is recommended that pathologic examination include serial sectioning of specimens. In practice, risk-reducing salpingo-oophorectomy is performed by both gynecologic oncologists and general gynecologists. To ensure optimal detection of occult malignancy, standardized adherence to outlined guidelines is necessary. OBJECTIVE: This study aimed to evaluate the adherence to optimal surgical and pathologic examination guidelines and to compare the rate of occult malignancy at the time of surgery between 2 provider types. STUDY DESIGN: Institutional review board exemption was obtained. A retrospective review of patients undergoing risk-reducing bilateral salpingo-oophorectomy without hysterectomy from October 1, 2015, to December 31, 2020, at 3 sites within a healthcare system was conducted. The inclusion criteria included age ≥18 years and a documented indication for surgery being a mutation in BRCA1 or BRCA2 or a strong family history of breast and/or ovarian cancer. Compliance with 5 surgical steps and pathologic specimen preparation was based on medical record documentation. Multivariable logistic regression was used to determine differences in adherence between provider groups and surgical and pathologic examination guidelines. A P value of <.025 was considered statistically significant for the 2 primary outcomes after Bonferroni correction was applied to adjust for multiple comparisons. RESULTS: A total of 185 patients were included. Among the 96 cases performed by gynecologic oncologists, 69 (72%) performed all 5 steps of surgery, 22 (23%) performed 4 steps, 5 (5%) performed 3 steps, and none performed 1 or 2 steps. Among the 89 cases performed by general gynecologists, 4 (5%) performed all 5 steps, 33 (37%) performed 4 steps, 38 (43%) performed 3 steps, 13 (15%) performed 2 steps, and 1 (1%) performed 1 step. Gynecologic oncologists were more likely to document adherence to all 5 recommended surgical steps in their surgical dictation (odds ratio, 54.3; 95% confidence interval, 18.1-162.7; P<.0001). Among the 96 cases documented by gynecologic oncologists, 41 (43%) had serial sectioning of all specimens performed, compared with 23 of 89 cases (26%) performed by general gynecologists. No difference in adherence to pathologic guidelines was identified between the 2 provider groups (P=.0489; note: P value of >.025). Overall, 5 patients (2.70%) had occult malignancy diagnosed at the time of risk-reducing surgery, with all surgeries performed by general gynecologists. CONCLUSION: Our results demonstrated greater compliance with surgical guidelines for risk-reducing bilateral salpingo-oophorectomy in gynecologic oncologists than in general gynecologists. No considerable difference was determined between the 2 provider types in adherence to pathologic guidelines. Our findings demonstrated a need for institution-wide protocol education and implementation of standardized nomenclature to ensure provider adherence to evidence-based guidelines.

Anti-NMDA receptor encephalitis with neurologic sequelae refractory to conservative therapy with complete response to adjuvant therapy.

BACKGROUND: Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis has been described in increasing frequency in association with benign, mature ovarian teratoma. Affected patients typically present with paraneoplastic limbic encephalitis with flu-like symptoms followed by altered mental status, acute psychiatric symptoms, seizures and amnesia. These symptoms can rapidly progressive if not treated aggressively with surgical resection. Profound neurological symptoms may require immunotherapy. CASE: We present a case of anti-NMDA receptor encephalitis associated with a malignant immature teratoma in which symptoms were refractory to surgical management and initial immunotherapy. A complete neurologic response was only seen after initiating adjuvant chemotherapy. CONCLUSION: Anti-NMDA receptor encephalitis has rarely been described with immature ovarian teratomas. In these cases, a complete response may not be observed until systemic chemotherapy is started.

Overall Survival and Adjuvant Therapy in Women with Ovarian Carcinosarcoma: A Single-Institution Experience.

BACKGROUND: Carcinosarcoma of the ovary (CSO) is a rare and aggressive variant of ovarian cancer. Due to the rare nature of the disease there is insufficient evidence to make recommendations regarding standard management and overall prognosis. METHODS: An Institutional Review Board-approved study identified all our patients with CSO between January 2011 and May 2018. Demographic and outcome measures were abstracted from the medical records and tumor board files. Cox proportional hazard models, log rank tests, and comparisons of means were used to calculate significance (p < 0.05). RESULTS: 27 women with CSO were identified. The median age at diagnosis was 65 years (range 48-91). Five women (18%) presented with early stage disease (Stage I or II) and 22 patients (82%) presented with late stage III or IV disease. Twenty patients (74%) received intravenous platinum-based combination chemotherapy. Seven patients did not receive chemotherapy during their treatment course. The median overall survival was 23 months (range 2-68 months). Overall survival was not significantly worsened by the stage of disease at diagnosis. There was no difference in survival based on the age at diagnosis, tobacco status or ethnicity (p > 0.05). CONCLUSION: This is one of the largest single institution experiences with CSO. The majority of our patients presented with advanced stage disease and received adjuvant platinum-based chemotherapy after cytoreductive surgery. The median overall survival of 23 months was not affected by the stage of the disease. The optimal management of this rare disease needs further study with collaborative, prospective multi-institutional trials.

In vivo oocyte retrieval in a young woman with ovarian cancer.

BACKGROUND: Oocyte cryopreservation is rapidly becoming an option for single women recently diagnosed with cancer who wish to preserve their fertility. We describe oocyte retrieval in young women with invasive ovarian cancer. CASE: A 23-year-old nulliparous woman had recurrence of a mixed ovarian germ cell tumor after unilateral oophorectomy. Concern of involvement of her remaining ovary and need for postoperative chemotherapy prompted decision to perform controlled ovarian hyperstimulation followed by intraoperative in vivo oocyte retrieval. CONCLUSION: Oocyte cryopreservation through controlled ovarian hyperstimulation leading up to oocyte retrieval at the time of surgical staging for gynecologic malignancies can be coordinated in a timely fashion, affording fertility preservation without significant treatment delay. Greater awareness of this capability may prompt extension of oocyte cryopreservation services to all potential candidates and help mobilize the establishment of referral pathways and multidisciplinary teams of general gynecologists, gynecologic oncologists, and reproductive endocrinologists.

Lymph node dissection in the surgical management of atypical endometrial hyperplasia.

OBJECTIVE: The aim of this study was to evaluate the effect of lymph node dissection in patients with atypical endometrial hyperplasia. STUDY DESIGN: Patients undergoing surgical management of atypical endometrial hyperplasia during the study period were retrospectively identified. Clinical and pathologic information was analyzed. RESULTS: Eighty-eight patients comprised our cohort. Median age was 54 years (range, 37-85 years). Sixty-seven patients had lymph node dissection at the time of surgery for atypical endometrial hyperplasia, whereas 21 did not. Twenty-five of 88 (28.4%) had endometrial carcinoma on final uterine pathology. Stages were as follows: 4 IA, 15 IB, 3 IC, 2 IIB, and 1 IIIC. Surgical outcomes were not statistically significant between staged and unstaged groups. Information from lymph node dissection influenced management decisions in 7 of the 25 (28%) cancer patients. CONCLUSION: Lymph node dissection did not adversely affect surgical outcomes in patients with atypical endometrial hyperplasia. Because many of these patients have concurrent endometrial cancer, we recommend consideration of lymph node dissection in atypical endometrial hyperplasia patients undergoing definitive surgical treatment.

LPA receptor 2 mediates LPA-induced endometrial cancer invasion.

OBJECTIVE: We have previously shown that lysophosphatidic acid (LPA) promotes the ovarian cancer metastatic cascade. In this study, we evaluated the role of LPA on endometrial cancer invasion. METHODS: Transient mRNA knockdown was accomplished using pre-designed siRNA duplexes against LPA receptor 2 (LPA2) and human matrix metalloproteinase-7 (MMP-7). RT-PCR was used to characterize LPA receptor and MMP-7 expression. Analysis of in vitro invasion was performed with rat-tail collagen type I coated Boyden chambers. Gelatin zymography was used to evaluate the MMP activity in cell culture conditioned media. Cell-cell and cell-matrix attachment was also assessed upon LPA2 knockdown to further illuminate the LPA2 cascade. RESULTS: LPA increases HEC1A cellular invasion at physiologic concentrations (0.1-1 muM). Of the four principle LPA receptors, LPA2 is predominantly expressed by HEC1A cells. Transient transfection of LPA2 siRNA reduced LPA2 mRNA expression in HEC1A cells by 93% (P<0.01). Silencing LPA2 eliminated the LPA-stimulated increase in invasion (P<0.05) and reduced LPA-induced MMP-7 secretion/activation, without significantly affecting cell-cell or cell-matrix adhesion. Silencing MMP-7 reduced overall invasion but did not eliminate LPA's pro-invasive effect on HEC1A cells, as compared to negative control (P<0.05). Gelatin zymography confirmed that LPA2 and MMP-7 knockdown reduced MMP-7 activation in HEC1A conditioned media. CONCLUSION: LPA2 mediates LPA-stimulated HEC1A invasion and the subsequent activation of MMP-7.