Attitudes and beliefs regarding complementary and alternative medicine in a diverse gynecologic oncology patient population.

Objectives: To measure prevalence of complementary and alternative medicine (CAM) use in a diverse gynecologic oncology patient population and evaluate how attitudes and beliefs regarding CAM relate to demographic factors. Methods: A validated Attitudes and Beliefs about Complementary and Alternative Medicine (ABCAM) survey was distributed to patients with gynecologic malignancy. Results were evaluated using Pearson's Chi-squared and Fisher's exact tests for categorical variables and Wilcoxon ranks sum and Kruskal-Wallace tests for non-normally distributed variables. Results: One-hundred thirty patients completed the ABCAM survey. Self-reported race and ethnicity included Asian or Pacific Islander (n = 54; 42%), Hispanic/Latino (n = 23; 18%), White (n = 21; 16%), Black or African American (n = 20; 15%), American Indian/Alaska Native (n = 8; 6.2%) and Other (n = 4; 3.1%). Twenty-four respondents (18%) reported use of CAM. There was a significant difference in expected benefits to CAM between respondents of different races/ethnicities (p < 0.001). Black and Asian respondents reported greater expected benefit to CAM. Hispanic/Latino, American Indian/Alaskan Native, and White respondents reported fewer expected benefits. A significant association was found between perceived barriers to CAM and race/ethnicity (p 0.043), with Asian, Hispanic/Latino and White respondents perceiving more barriers while Black and American Indian/Alaskan Natives reported perceiving fewer barriers to CAM. Respondents with incomes greater than $100,000 reported fewer barriers to CAM. Conclusions: Use of CAM among gynecologic oncology patients is lower than previously thought. Income, race, and ethnicity inform patient engagement with CAM and can be used to better tailor the provision of evidence-based CAM interventions to benefit a greater number of gynecologic cancer patients.

Adoption of minimally invasive surgery after neoadjuvant chemotherapy in women with metastatic uterine cancer.

OBJECTIVE: Utilization of neoadjuvant chemotherapy (NACT) for advanced stage uterine cancer is increasing. We analyzed the use and outcomes of open versus minimally invasive surgery (MIS) for women with stage IV uterine cancer who received NACT and underwent IDS. METHODS: The National Cancer Database was used to identify women with stage IV uterine cancer diagnosed from 2010 to 2017 and treated with NACT. Among women who underwent IDS, overall survival (OS) was compared between those who underwent laparotomy vs a minimally invasive approach. To account for imbalances in confounders, a propensity score analysis using inverse probability of treatment weighting (IPTW) was performed. RESULTS: A total of 1618 women were identified. Minimally invasive IDS was performed in 31.1% and increased from 16.2% in 2010 to 40.4% in 2017 (P < 0.001). More recent year of diagnosis and performance of surgery at a comprehensive cancer center were associated with increased use of MIS (P < 0.05). Women with serous and clear cell tumors, and carcinosarcomas (compared to endometrioid tumors), as well as Medicaid coverage (compared to commercial insurance) were less likely to undergo an MIS approach (P < 0.05). The median OS was 28 months (95% CI 23.7-30.7) and 24.3 months (95% CI 22.3-26.1) for MIS and laparotomy, respectively. After propensity score balancing, there was no association between the use of MIS and survival (HR = 0.90, 95% CI 0.71-1.14). CONCLUSIONS: Among women with stage IV uterine cancer treated with NACT performance of minimally invasive debulking surgery is increasing. Compared to laparotomy, MIS does not appear to negatively impact survival.

Leveraging Health Information Technology to Collect Family Cancer History: A Systematic Review and Meta-Analysis.

PURPOSE: Collection of family cancer histories (FCHs) can identify individuals at risk for familial cancer syndromes. The aim of this study is to evaluate the literature on existing strategies whereby providers use information technology to assemble FCH. METHODS: A systematic search of online databases (Ovid MEDLINE, Cochrane, and Embase) between 1980 and 2020 was performed. Statistical heterogeneity was assessed through the chi-square test (ie, Cochrane Q test) and the inconsistency statistic (I2). A random-effects analysis was used to calculate the pooled proportions and means. RESULTS: The comprehensive search produced 4,005 publications. Twenty-eight studies met inclusion criteria. Twenty-seven information technology tools were evaluated. Eighteen out of 28 studies were electronic surveys administered before visits (18, 64.3%). Five studies administered tablet surveys in offices (5, 17.8%). Four studies collected electronic survey via kiosk before visits (4, 14.3%), and one study used animated virtual counselor during visits (1, 3.6%). Among the studies that use an FCH tool, the pooled estimate of the overall completion rate was 86% (CI, 72% to 96%), 84% (CI, 65% to 97%) for electronic surveys before visits, 89% (CI, 0.74 to 0.98) for tablet surveys, and 85% (CI, 0.66 to 0.98) for surveys via kiosk. Mean time required for completion was 31.0 minutes (CI, 26.1 to 35.9), and the pooled estimate of proportions of participants referred to genetic testing was 12% (CI, 4% to 23%). CONCLUSION: Our review found that electronic FCH collection can be completed successfully by patients in a time-efficient manner with high rates of satisfaction.

Financial toxicity, mental health, and gynecologic cancer treatment: The effect of the COVID-19 pandemic among low-income women in New York City.

BACKGROUND: New York City (NYC) emerged as an epicenter of the COVID-19 pandemic, and marginalized populations were affected at disproportionate rates. The authors sought to determine the impact of COVID-19 on cancer treatment, anxiety, and financial distress among low-income patients with gynecologic cancer during the peak of the NYC pandemic. METHODS: Medicaid-insured women who were receiving gynecologic oncology care at 2 affiliated centers were contacted by telephone interviews between March 15 and April 15, 2020. Demographics and clinical characteristics were obtained through self-report and retrospective chart review. Financial toxicity, anxiety, and cancer worry were assessed using modified, validated surveys. RESULTS: In total, 100 patients completed the telephone interview. The median age was 60 years (range, 19-86 years), and 71% had an annual income <$40,000. A change in employment status and early stage cancer (stage I and II) were associated with an increase in financial distress (P < .001 and P = .008, respectively). Early stage cancer and telehealth participation were significantly associated with increased worry about future finances (P = .017 and P = .04, respectively). Lower annual income (<$40,000) was associated with increased cancer worry and anxiety compared with higher annual income (>$40,000; P = .036 and P = .017, respectively). When controlling for telehealth participation, income, primary language, and residence in a high COVID-19 prevalence area, a delay in medical care resulted in a 4-fold increased rate of anxiety (P = .023, 95% CI, 1.278-14.50). Race was not significantly associated with increased financial distress, cancer worry, or anxiety. CONCLUSIONS: Low socioeconomic status was the most common risk factor for increased financial distress, cancer worry, and anxiety. Interventions aimed at improving access to timely oncology care should be implemented during this ongoing pandemic.

Combination uterine artery embolization and hysteroscopic resection for a symptomatic uterine leiomyoma: A collaborative single-session approach for better patient care.

Uterine artery embolization (UAE) for symptomatic uterine fibroids is accompanied by transcervical fibroid expulsion in 3-15% of cases. It can be a source of significant patient distress, may require reintervention for removal, and is the most common reason for hospital readmission following UAE. Conversely, the success of hysteroscopic resection decreases with increasing fibroid size while the risk of complications increases. Because certain fibroid features identifiable on preoperative imaging predict need for eventual hysteroscopic resection, it is possible to prospectively identify such patients and employ an alternative management strategy. We present such an approach, illustrated in the case of a woman with a pedunculated broad-based uterine fibroid successfully managed via combination UAE and immediate hysteroscopic resection.

Racial and Ethnic Disparities in Genetic Testing at a Hereditary Breast and Ovarian Cancer Center.

BACKGROUND: Prior studies suggest that referral to genetic counseling and completion of genetic testing vary by race/ethnicity; however, the data are limited. OBJECTIVE: We sought to evaluate patterns of genetic testing and clinical outcomes across race/ethnicity at a hereditary breast and ovarian cancer center. DESIGN: The medical records for all patients undergoing genetic assessment at a hereditary breast and ovarian cancer center were reviewed and stratified by self-reported race/ethnicity (non-Hispanic White, Hispanic, non-Hispanic Black, and Asian). PARTICIPANTS: A total of 1666 patients met inclusion criteria (non-Hispanic Whites, 1367; Hispanics, 85, non-Hispanic Blacks, 101; Asians, 113). MAIN MEASURES: Demographics, patient characteristics, and referral patterns for patients who underwent genetic testing were analyzed using Kruskal-Wallis tests, chi-square test, or Fisher's exact tests, stratifying by self-reported race/ethnicity. Pathogenic mutations and variants of unknown significance (VUS) were reviewed. Outcomes of patients with genetic mutations and personal history of breast and/or gynecologic malignancies were compared. KEY RESULTS: Non-Hispanic Whites were more likely to be referred due to family cancer history compared to all other ethnicities while Non-Hispanic Blacks, Hispanics, and Asians were more likely to be referred due to personal history of cancer (p < 0.001). Non-Hispanic Blacks and Hispanics were more likely to have advanced-stage cancer at the time of genetic testing (p < 0.02). Rates of mutations did not differ by race/ethnicity when Ashkenazi Jewish patients were excluded (p = 0.08). Among patients found to have a BRCA1/2 mutation, Non-Hispanic Whites were more likely to undergo cancer screening and risk-reducing surgery compared with all other ethnicities (p = 0.04). CONCLUSIONS: Minority patients were more likely to utilize genetic services following a cancer diagnosis and less likely due to family cancer history, suggesting a missed opportunity for mutation detection and cancer prevention in this population. Efforts to eradicate racial/ethnic disparities in early access to genetic testing and guided cancer prevention strategies are essential.

Perioperative Morbidity and Mortality of Patients With COVID-19 Who Undergo Urgent and Emergent Surgical Procedures.

OBJECTIVE: To evaluate the perioperative morbidity and mortality of patients with COVID-19 who undergo urgent and emergent surgery. SUMMARY BACKGROUND DATA: Although COVID-19 infection is usually associated with mild disease, it can lead to severe respiratory complications. Little is known about the perioperative outcomes of patients with COVID-19. METHODS: We examined patients who underwent urgent and emergent surgery at 2 hospitals in New York City from March 17 to April 15, 2020. Elective surgical procedures were cancelled throughout and routine, laboratory based COVID-19 screening was instituted on April 1. Mortality, complications, and admission to the intensive care unit were compared between patients with COVID-19 detected perioperatively and controls. RESULTS: Among 468 subjects, 36 (7.7%) had confirmed COVID-19. Among those with COVID-19, 55.6% were detected preoperatively and 44.4% postoperatively. Before the routine preoperative COVID-19 laboratory screening, 7.7% of cases were diagnosed preoperatively compared to 65.2% after institution of screening (P = 0.0008). The perioperative mortality rate was 16.7% in those with COVID-19 compared to 1.4% in COVID-19 negative subjects [aRR = 9.29; 95% confidence interval (CI), 5.68-15.21]. Serious complications were identified in 58.3% of COVID-19 subjects versus 6.0% of controls (aRR = 7.02; 95%CI, 4.96-9.92). Cardiac arrest, sepsis/shock, respiratory failure, pneumonia, acute respiratory distress syndrome, and acute kidney injury were more common in those with COVID-19. The intensive care unit admission rate was 36.1% in those with COVID-19 compared to 16.4% of controls (aRR = 1.34; 95%CI, 0.86-2.09). CONCLUSIONS: COVID-19 is associated with an increased risk for serious perioperative morbidity and mortality. A substantial number of patients with COVID-19 are not identified until after surgery.

Coronavirus Spectrum Infections (COVID-19, MERS, SARS) in Cancer Patients: A Systematic Review of the Literature.

BACKGROUND: Coronavirus 2019 (COVID-19) has spread rapidly around the world to become a global pandemic. There is limited data on the impact of COVID-19 among patients with cancer. METHODS: A systematic review was performed to determine outcomes of adult patients with cancer affected by coronavirus infections, specifically SARS, MERS, and COVID-19. Studies were independently screened by two reviewers and assessed for quality and bias. Outcomes measured included study characteristics, cancer type, phase of care at the time of diagnosis, and clinical presentation. Morbidity and mortality outcomes were analyzed to assess the severity of infection as compared to the general population. RESULTS: A total of 19 studies with 110 patients were included. Of these, 66.4% had COVID-19 infections, 32.7% MERS and only one patient with SARS. The majority of COVID-19 studies were based on studies in China. There was a 56.6% rate of a severe event, including ICU admission or requiring mechanical ventilation, with an overall 44.5% fatality rate. CONCLUSIONS: Patients with cancer with coronavirus infections may be more susceptible to higher morbidity and mortality.

Is hysterectomy necessary for the treatment of preinvasive stratified mucin producing intraepithelial lesions of the cervix?

OBJECTIVES: Stratified mucin producing intraepithelial lesion (SMILE) is an uncommon premalignant cervical intraepithelial lesion, characterized by histopathologic features resembling those observed in high grade squamous intraepithelial lesions and adenocarcinoma in situ of the cervix. Its hybrid morphology poses a pathologic challenge with no specific management guidelines. The goal of this study was to review the natural history of SMILE and treatment based outcomes. METHODS: A retrospective pathology review of all cases of cervical intraepithelial lesions, with confirmation of all SMILE lesions, at one institution between 2007 and 2019, was performed. Clinical and pathologic characteristics, management options, and patient outcomes were reviewed and analyzed. Inclusion criteria included all patients diagnosed initially with SMILE on biopsy, excisional procedure, or simple hysterectomy. Patients diagnosed with SMILE had to fulfill the following pathologic features: stratified columnar epithelium with nuclear atypia and mucin production throughout the epithelial thickness with increased mitotic activity, and/or apoptotic bodies. Pathologic slides were re-evaluated by a pathologist to confirm the diagnosis and review margin status. RESULTS: 24 patients with SMILE were identified. Mean age at diagnosis was 36.2 years (range 25-53) with 67% (16/24) diagnosed before the age of 40. The majority (54%, 13/24) were nulliparous and 63% (15/24) had a past history of abnormal Pap smears. 92% (22/24) of patients were positive for high risk human papillomavirus, with 13% (n=3) presenting with a normal Pap smear. Diagnosis was made primarily on colposcopy (n=16), cold knife cone/loop electrosurgical excision procedure (n=7), or hysterectomy (n=1). Most patients (71%, 17/24) had a co-existing precancerous lesion at the time of diagnosis and the most common was high grade squamous intraepithelial lesion (53%). Five invasive lesions were also identified at the time of diagnosis of SMILE (2 adenocarcinoma, 3 adenosquamous), 1 of which underwent chemoradiation. Among all patients, 25% (6/24) underwent hysterectomy (4 simple, 2 radical), while 63% (17/24) of patients underwent a fertility sparing excisional procedure; 4% (1/24) were incidentally diagnosed on hysterectomy. 18 patients had negative margins and 2 patients had positive margins. Over a median follow-up of 29 months (range 3-105), all of the fertility sparing patients with negative margins had no recurrence. Among the two patients with positive margins, one had no recurrence on repeat excision and the other underwent repeat excision with persistent SMILE identified, subsequent negative margin, and no recurrence since. DISCUSSION: Our data showed that most patients with SMILE were young, positive for high risk human papillomavirus, nulliparous, and presented with coexisting lesions. Excisional procedures with negative margins may be sufficient fertility sparing treatment in patients with preinvasive SMILE with a low risk of recurrence. There should be consideration of hysterectomy at the completion of childbearing.

Cauda equina syndrome secondary to leptomeningeal metastases from recurrent primary peritoneal carcinoma.

The patient is a 42-year-old woman with metastatic primary peritoneal carcinoma and known brain metastases, who subsequently developed cauda equina syndrome after presenting with ataxia, lower extremity weakness, and bowel and bladder incontinence secondary to leptomeningeal metastasis after treatment with neoadjuvant chemotherapy, surgical debulking, and adjuvant chemotherapy. Metastases to the central nervous system (CNS) and leptomeninges are rare events in epithelial ovarian and primary peritoneal carcinomas as these tumours do not have a predilection for the CNS. Cauda equina syndrome is often characterised by gait disturbances, bowel and bladder dysfunction, saddle anaesthesia, and lower extremity muscle weakness. In patients with known metastatic gynaecologic carcinomas presenting with nonspecific neurologic symptoms, cauda equina syndrome should remain high in the differential diagnosis.

Ruptured clear cell carcinoma of the ovary presenting as acute abdomen.

BACKGROUND: Ovarian cancer remains one of the leading causes of cancer-related deaths among women. Clear cell ovarian carcinoma is a rare histologic subtype accounting for 5-10% of all epithelial ovarian cancers and is often associated with endometriosis. Patients generally present with vague abdominal and pelvic complaints. However, patients can present in the acute setting with pleural effusions, ascites, bowel obstructions, and deep vein thrombosis. CASE: A 54 year old woman presenting with an acute abdomen secondary to rupture of ovarian clear cell carcinoma. CONCLUSION: Ovarian clear cell carcinoma should remain in the differential diagnosis in a patient presenting with an acute abdomen and imaging suspicious for a gynecologic malignancy originating from the ovary.

Slug promotes survival during metastasis through suppression of Puma-mediated apoptosis.

Tumor cells must overcome apoptosis to survive throughout metastatic dissemination and distal organ colonization. Here, we show in the Polyoma Middle T mammary tumor model that N-cadherin (Cdh2) expression causes Slug (Snai2) upregulation, which in turn promotes carcinoma cell survival. Slug was dramatically upregulated in metastases relative to primary tumors. Consistent with a role in metastasis, Slug knockdown in carcinoma cells suppressed lung colonization by decreasing cell survival at metastatic sites, but had no effect on tumor cell invasion or extravasation. In support of this idea, Slug inhibition by shRNA sensitized tumor cells to apoptosis by DNA damage, resulting in caspase-3 and PARP cleavage. The prosurvival effect of Slug was found to be caused by direct repression of the proapoptotic gene, Puma (Bbc3), by Slug. Consistent with a pivotal role for a Slug-Puma axis in metastasis, inhibition of Puma by RNA interference in Slug-knockdown cells rescued lung colonization, whereas Puma overexpression in control tumor cells suppressed lung metastasis. The survival function of the Slug-Puma axis was confirmed in human breast cancer cells, where Slug knockdown increased Puma expression and inhibited lung colonization. This study demonstrates a pivotal role for Slug in carcinoma cell survival, implying that disruption of the Slug-Puma axis may impinge on the survival of metastatic cells.

Contribution of CXCL12 secretion to invasion of breast cancer cells.

INTRODUCTION: Neu (HER2/ErbB2) is overexpressed in 25% to 30% of human breast cancer, correlating with a poor prognosis. Researchers in previous studies who used the mouse mammary tumor virus Neu-transgenic mouse model (MMTV-Neu) demonstrated that the Neu-YB line had increased production of CXCL12 and increased metastasis, whereas the Neu-YD line had decreased metastasis. In this study, we examined the role of increased production of CXCL12 in tumor cell invasion and malignancy. METHODS: We studied invasion in the tumor microenvironment using multiphoton intravital imaging, in vivo invasion and intravasation assays. CXCL12 signaling was altered by using the CXCR4 inhibitor AMD3100 or by increasing CXCL12 expression. The role of macrophage signaling in vivo was determined using a colony-stimulating factor 1 receptor (CSF-1R) blocking antibody. RESULTS: The Neu-YD strain was reduced in invasion, intravasation and metastasis compared to the Neu-YB and Neu deletion mutant (activated receptor) strains. Remarkably, in the Neu-YB strain, in vivo invasion to epidermal growth factor was dependent on both CXCL12-CXCR4 and CSF1-CSF-1R signaling. Neu-YB tumors had increased macrophage and microvessel density. Overexpression of CXCL12 in rat mammary adenocarcinoma cells increased in vivo invasion as well as microvessel and macrophage density. CONCLUSIONS: Expression of CXCL12 by tumor cells results in increased macrophage and microvessel density and in vivo invasiveness.

Tumor-stroma: In vivo assays and intravital imaging to study cell migration and metastasis.

The development of metastatic disease is often correlated with poor patient outcome in a variety of different cancers. The metastatic cascade is a complex, multistep process that involves the growth of the primary tumor and angiogenesis, invasion into the local environment, intravasation into the vasculature, tumor cell survival in the circulation, extravasation from the vasculature and sustained growth at secondary organ sites to form metastases. Although in vitro assays of single cell types can provide information regarding cell autonomous mechanisms contributing to metastasis, the in vivo microenvironment entails a network of interactions between cells which is also important. Insight into the mechanisms underlying tumor cell migration, invasion and metastasis in vivo has been aided by development of multiphoton microscopy and in vivo assays, which we will review here.