The effect of older age on treatment outcomes in women with advanced ovarian cancer receiving chemotherapy: An NRG-Oncology/Gynecologic Oncology Group (GOG-0182-ICON5) ancillary study.

OBJECTIVE: To assess the effect of age on overall survival (OS) in women with ovarian cancer receiving chemotherapy. Secondary objectives were to describe the effect of age on treatment compliance, toxicities, progression free survival (PFS), time from surgery to chemotherapy, and rates of optimal cytoreduction. METHODS: Women enrolled in GOG 0182-ICON5 with stage III or IV epithelial ovarian cancer (EOC) who underwent surgery and chemotherapy between 2001 and 2004 were included. Patients were divided into ages <70 and ≥ 70 years. Baseline characteristics, treatment compliance, toxicities, and clinical outcomes were compared. RESULTS: We included a total of 3686 patients, with 620 patients (16.8%) ≥ 70 years. OS was 37.2 months in older compared to 45.0 months in younger patients (HR 1.21, 95% CI, 1.09-1.34, p < 0.001). Older patients had an increased risk of cancer-specific-death (HR 1.16, 95% CI, 1.04-1.29) as well as non-cancer related deaths (HR 2.78, 95% CI, 2.00-3.87). Median PFS was 15.1 months in older compared to 16.0 months in younger patients (HR 1.10, 95% CI, 1.00-1.20, p = 0.056). In the carboplatin/paclitaxel arm, older patients were just as likely to complete therapy and more likely to develop grade ≥ 2 peripheral neuropathy (35.7 vs 19.7%, p < 0.001). Risk of other toxicities remained equal between groups. CONCLUSIONS: In women with advanced EOC receiving chemotherapy, age ≥ 70 was associated with shorter OS and cancer specific survival. Older patients receiving carboplatin and paclitaxel reported higher rates of grade ≥ 2 neuropathy but were not more likely to suffer from other chemotherapy related toxicities. Clintrials.gov: NCT00011986.

Intestinal type adenocarcinoma of the endometrium with signet ring cells, a rare aggressive variant.

Objective: Intestinal type mucinous adenocarcinoma (iMACE) is a rare and unusual variant of mucinous carcinoma of the endometrium that can show focal features of poorly differentiated adenocarcinomas of gastric, pancreatic or intestinal origin by producing signet ring cells. To date, only two reported cases of signet ring cells as a morphological feature of iMACE have been reported. Alterations in E-cadherin expression have been linked to increased metastatic potential, tumor dedifferentiation, and deep myometrial invasion in endometrial carcinomas. The presence or absence of E-cadherin in iMACE with signet-ring cells has not been studied. Thus, we sought to analyze E-cadherin expression in this aggressive variant of endometrial carcinoma. Cases: Diagnosis of iMACE with signet ring cells was rendered with the aid of immunohistochemical staining and histological analysis. Average age of diagnosis was 72 with the presenting complaint of postmenopausal bleeding in all three women. Focal loss or weakly positive E-cadherin expression was seen in areas of signet-rings cell morphology in all three cases. Conclusion: This case report adds to the body of literature that demonstrates the aggressive nature of intestinal differentiation in the endometrium. In addition, this report suggests that the presence of signet-rings cells and loss of E-cadherin expression may render a poorer prognosis as seen in other parts of the body.

Nosocomial COVID-19 infection in women undergoing elective cesarean delivery: a prospective cohort study.

BACKGROUND: The COVID-19 pandemic placed obstetricians in a difficult position of continuing to perform elective cesarean delivery without the knowledge of the risk of the spread of nosocomial infection of the COVID-19 virus. OBJECTIVE: This study aimed to determine the nosocomial infection rate in women undergoing elective cesarean delivery at 2 academic institutions. STUDY DESIGN: This nonrandomized prospective cohort trial evaluated patients undergoing elective cesarean delivery during the reopening phase of the COVID-19 pandemic in the state of New York at 2 large volume labor and delivery units. Eligible patients with a negative preoperative reverse transcriptase-polymerase chain reaction test and immunoglobulin G antibody test for COVID-19 were retested 6 to 9 days after discharge. The primary objective was the COVID-19 test conversion rate defined as a positive polymerase chain reaction test for SARS-CoV-2 after discharge with a negative preoperative test. This was used as a proxy for the nosocomial infection rate. RESULTS: A total of 136 patients were screened for participation. Of these patients, 2 tested positive for COVID-19 on preoperative testing, and 25 declined to participate. Overall, 111 patients consented to participate, and 96 patients underwent both preoperative and postoperative testing. No patient with a negative polymerase chain reaction test preoperatively, had a positive polymerase chain reaction test for the COVID-19 virus postoperatively. CONCLUSION: With strict and methodical perioperative and postpartum protocols, we can limit nosocomial COVID-19 infection in women undergoing elective cesarean delivery.

Toward the Quadruple Aim: Impact of a Humanistic Mentoring Program to Reduce Burnout and Foster Resilience.

OBJECTIVE: To assess the effect of a faculty development program (Mentoring and Professionalism in Training [MAP-IT]) that fosters humanism in medicine on elements of burnout and the development of resilience. PARTICIPANTS AND METHODS: The cohort of participants was drawn from a cross-section of disciplines and represented a diverse group of health professionals, including physicians, nurses, physician assistants, pharmacists, psychologists, social workers, and chaplains. The 106 participants were divided into 12 groups, each of which was facilitated by two or three leaders. Each group completed the MAP-IT curriculum from October 1, 2017, through July 31, 2018. All participants and leaders completed the Connor-Davidson Resilience Scale and the Maslach Burnout Inventory (assessing emotional exhaustion, depersonalization, and personal accomplishment) before and after completion of the program. RESULTS: The participants' scores for emotional exhaustion and depersonalization remained unchanged following the completion of the MAP-IT curriculum. However, their scores for personal accomplishment and resilience increased significantly and approximated those of the leaders. CONCLUSION: The MAP-IT program has shown effectiveness both in fostering resilience and a sense of personal accomplishment. The time is ripe for institutional programming to create and foster the personal tools needed to prevent burnout and its sequelae.

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.

Correction: Identification of grade and origin specific cell populations in serous epithelial ovarian cancer by single cell RNA-seq.

[This corrects the article DOI: 10.1371/journal.pone.0206785.].

Identification of grade and origin specific cell populations in serous epithelial ovarian cancer by single cell RNA-seq.

Here we investigated different cell populations within ovarian cancer using single-cell RNA seq: fourteen samples from nine patients with differing grades (high grade, low grade and benign) as well as different origin sites (primary and metastatic tumor site, ovarian in origin and fallopian in origin). We were able to identify sixteen distinct cell populations with specific cells correlated to high grade tumors, low grade tumors, benign and one population unique to a patient with a breast cancer relapse. Furthermore the proportion of these populations changes from primary to metastatic in a shift from mainly epithelial cells to leukocytes with few cancer epithelial cells in the metastases. Differential gene expression shows myeloid lineage cells are the primary cell group expressing soluble factors in primary samples while fibroblasts do so in metastatic samples. The leukocytes that were captured did not seem to be suppressed through known pro-tumor cytokines from any of the cell populations. Single cell RNA-seq is necessary to de-tangle cellular heterogeneity for better understanding of ovarian cancer progression.

Two microRNA signatures for malignancy and immune infiltration predict overall survival in advanced epithelial ovarian cancer.

MicroRNAs have been established as key regulators of tumor gene expression and as prime biomarker candidates for clinical phenotypes in epithelial ovarian cancer (EOC). We analyzed the coexpression and regulatory structure of microRNAs and their co-localized gene targets in primary tumor tissue of 20 patients with advanced EOC in order to construct a regulatory signature for clinical prognosis. We performed an integrative analysis to identify two prognostic microRNA/mRNA coexpression modules, each enriched for consistent biological functions. One module, enriched for malignancy-related functions, was found to be upregulated in malignant versus benign samples. The second module, enriched for immune-related functions, was strongly correlated with imputed intratumoral immune infiltrates of T cells, natural killer cells, cytotoxic lymphocytes, and macrophages. We validated the prognostic relevance of the immunological module microRNAs in the publicly available The Cancer Genome Atlas data set. These findings provide novel functional roles for microRNAs in the progression of advanced EOC and possible prognostic signatures for survival.

Metastatic Malignant Ovarian Steroid Cell Tumor: A Case Report and Review of the Literature.

We report a case of malignant ovarian steroid cell tumor not otherwise specified (NOS) in a 47-year-old female who presented with hirsutism, virilization, and amenorrhea. At the time of laparotomy, the tumor had already spread to the pelvic cul-de-sac. She underwent a total hysterectomy, bilateral salpingo-oophorectomy, and tumor resection with no residual disease. She received three cycles of bleomycin, etoposide, and cisplatin (BEP) and is now free of disease 24 months after surgery. Literature review of ovarian steroid cell tumors NOS including clinicopathological features and clinical management was performed.

Ovarian Sertoli-Leydig Cell Tumor with Predominant Heterologous Mucinous Differentiation and Foci of Hepatocytic Differentiation: Case Report and Review of The Literature.

Sertoli-Leydig cell tumor is a rare ovarian neoplasm and belongs to the group of sex cord stromal tumors. We present a case of a 15-year old girl diagnosed with Sertoli-Leydig cell tumor with heterologous elements consisting predominantly of mucinous epithelium and a sparse Sertoli-Leydig cell component, mimicking mucinous neoplasm. Furthermore, foci of hepatocytic differentiation were also identified. Immunohistochemical stains showed the component of Sertoli cell differentiation was positive for cytokeratin 18 and inhibin. The component of Leydig cell differentiation was strongly positive for inhibin. The component of hepatocytic differentiation was positive for low molecular weight keratin, HepPar1, alpha-fetoprotein and weakly positive for inhibin. Thus, this was a very rare case which created a challenge for pathologists, especially on frozen sections.

Mentoring program design and implementation in new medical schools.

PURPOSE: Mentoring is considered a valuable component of undergraduate medical education with a variety of programs at established medical schools. This study presents how new medical schools have set up mentoring programs as they have developed their curricula. METHODS: Administrators from 14 US medical schools established since 2006 were surveyed regarding the structure and implementation of their mentoring programs. RESULTS: The majority of new medical schools had mentoring programs that varied in structure and implementation. Although the programs were viewed as valuable at each institution, challenges when creating and implementing mentoring programs in new medical schools included time constraints for faculty and students, and lack of financial and professional incentives for faculty. CONCLUSIONS: Similar to established medical schools, there was little uniformity among mentoring programs at new medical schools, likely reflecting differences in curriculum and program goals. Outcome measures are needed to determine whether a best practice for mentoring can be established.

Education and experience with breast health maintenance and breast cancer care: a study of obstetricians and gynecologists.

Breast cancer is one of the most common malignancies in the United States. A survey regarding the practice, training, and knowledge of breast health maintenance and cancer screening was conducted with a response rate of 59%. Most respondents reported adequate knowledge and that continuing educational efforts were at least adequate. Most recognize the importance of family history and incorporate patient inquiry and referral to genetics practitioners into their practice. A considerable portion does not inquire about hereditary risk factors and feel "not qualified" to manage genetic counseling and screening. Continued training is needed about hereditary predisposition to breast disease.

Evaluation of vinorelbine in persistent or recurrent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study.

PURPOSE: Vinorelbine is being explored by the Gynecologic Oncology Group (GOG) for its possible use in advanced or recurrent squamous cell carcinoma of the uterine cervix. The objective of this Phase II trial was to evaluate a days 1 and 8 every-21-days schedule and determine its activity in patients who had failed standard chemotherapy. PATIENTS AND METHODS: Eligible patients with measurable disease and satisfactory baseline bone marrow, liver, and kidney functions were treated with vinorelbine 30 mg/m(2) given on days 1 and 8 every 21 days. A two-stage sampling design was used, proceeding to a second stage accrual if sufficient activity was documented in the first 25 patients. RESULTS: The study did proceed to the second stage and accrued 44 patients. There were six objective responses (one complete, five partial) for a response rate of 13.7% (95% confidence interval: 5.2-27.4%). There were three patients with response in extra-pelvic sites (including the complete response) and three with response in the pelvis. The overall frequency of grades 3 and 4 neutropenia was 41%, whereas neuropathy was reported in 27% and was severe in three. Treatment-related pain, very severe in two instances, was also reported in 27%. CONCLUSION: Vinorelbine has moderate activity in a pretreated population with squamous cell carcinoma of the cervix. Accordingly, vinorelbine in this days 1 and 8 schedule is being studied further in combination with cisplatin by the GOG.

Teaching operative dictation. A survey of obstetrics/gynecology residency program directors.

OBJECTIVE: To assess current efforts to teach operative dictation in obstetrics and gynecology residency programs. STUDY DESIGN: A survey detailing the didactics of operative dictation was distributed in a single mailing to all program directors listed in the roster of the Council on Residency Education in Obstetrics and Gynecology. RESULTS: Of 274 surveys distributed, 115 (42%) were returned. Ten percent of program directors reported defined curricula related to operative dictation. Using a combination of lectures, personal instruction and review of previous notes, attendings and senior residents share the responsibility for teaching operative dictation in the majority (78%) of programs. Sixty percent of program directors were in favor of more formal guidelines for residency education in the technique of operative dictation, 34% were opposed, and 6% offered no opinion. CONCLUSION: Obstetrics and gynecology residency programs rarely have a structured curriculum for teaching operative dictation, and the majority of program directors support the institution of more formal guidelines.