The burden of cervical cancer survivorship: Understanding morbidity and survivorship needs through hospital admissions.

Objective: To describe disease- and treatment-related survivorship burden amongst survivors of cervical cancer and identify risk factors for hospital admissions after initial treatment. Methods: Retrospective chart review including patients treated for cervical cancer from 2014 to 2020 at a single urban academic institution. Clinical, demographic, and hospital admission characteristics were summarized. Associations between patient characteristics and likelihood of admission were examined using univariate and multivariate regression. Results: Of 366 patients undergoing surveillance following completion of primary treatment, 156 (43 %) were hospitalized for cancer or treatment-related sequela in the median follow-up of 3.6 years (IQR 1.4-6.4), with a median of 2 admissions (IQR 1-4.5) per patient and 570 unique admissions. While 65 (35 %) of admitted patients had multiple reasons for admission, the most common reasons for admission were: gastrointestinal complications (43 %), infection (38 %), genitourinary complications (33 %), and pain control (23 %). A substantial proportion of admitted patients underwent interventions including surgical procedures (57 %), transfusion of blood products (40 %), and interventional radiology procedures (28 %) and utilized supportive care services including case management (53 %), physical therapy (40 %), and occupational therapy (36 %). On multivariate analysis, odds of admission were higher among Black patients (aOR 2.4, p <.01), uninsured patients (aOR 2.7, p <.05), those with lower performance status (aOR 1.4, p <.05), and those with recurrence (aOR 5.5, p <.001). Conclusion: Survivors of cervical cancer represent a high-risk population frequently hospitalized after initial treatment. Black patients, uninsured patients, those with recurrence, and those with lower performance status faced higher odds of admission. Comprehensive, team-based care is necessary to address complex survivorship needs.

Molecular portraits of clear cell ovarian and endometrial carcinoma with comparison to clear cell renal cell carcinoma.

OBJECTIVE: Advanced clear cell gynecologic malignancies remain among the most challenging diseases to manage. We evaluated ovarian and endometrial clear cell carcinoma (OCCC and ECCC) specimens using comprehensive sequencing technology to identify mutational targets and compared their molecular profiles to histologically similar clear cell renal cell carcinoma (ccRCC). METHODS: Using next-generation sequencing (NGS), fragment analysis (FA), and in situ hybridization (ISH), 164 OCCC, 75 ECCC and 234 ccRCC specimens from 2015 to 2018 were evaluated and compared. RESULTS: The highest mutation rates in ECCC and OCCC were noted in: ARID1A (75.0%, 87.5%), TP53 (34.8%, 11.1%), PIK3CA (25.0%, 46.8%), PPP2R1A (8.7%, 16.7%), MSI-high (8.8%, 6.4%) and PTEN (8.3%, 7.1%). Among these mutations, there was no significant difference between OCCC and ECCC mutation prevalence except in TP53, with higher mutation rates in ECCC versus OCCC (34.8 vs. 11.1%, respectively, p < 0.05). ccRCC demonstrated different mutation profiles with higher mutation rates in VHL (80.3%), PBRM1 (43.9%), SETD2 (31.1%), and KDM5C (29.2%). By contrast, VHL, PBRM1, and SETD2 mutations were not found in ECCC and OCCC (0.0%). Compared to ccRCC and ECCC, OCCC was found to have a significantly higher tumor mutation burden (TMB) (19.1%). CONCLUSION: Gynecologic and renal CCC demonstrate separate and disparate somatic profiles. However, OCCC and ECCC are diseases with similar profiles. TMB and MSI analyses indicate that a subset of OCCC may benefit from immunotherapy. Prospective clinical trials are needed and are underway to examine targeted therapies in these gynecologic disease subtypes.

A molecular atlas of the human postmenopausal fallopian tube and ovary from single-cell RNA and ATAC sequencing.

As part of the Human Cell Atlas Initiative, our goal is to generate single-cell transcriptomics (single-cell RNA sequencing [scRNA-seq], 86,708 cells) and regulatory (single-cell assay on transposase accessible chromatin sequencing [scATAC-seq], 59,830 cells) profiles of the normal postmenopausal ovary and fallopian tube (FT). The FT contains 11 major cell types, and the ovary contains 6. The dominating cell type in the FT and ovary is the stromal cell, which expresses aging-associated genes. FT epithelial cells express multiple ovarian cancer risk-associated genes (CCDC170, RND3, TACC2, STK33, and ADGB) and show active communication between fimbrial epithelial cells and ovarian stromal cells. Integrated single-cell transcriptomics and chromatin accessibility data show that the regulatory landscape of the fimbriae is different from other anatomic regions. Cell types with similar gene expression in the FT display transcriptional profiles. These findings allow us to disentangle the cellular makeup of the postmenopausal FT and ovary, advancing our knowledge of gynecologic diseases in menopause.

Surviving and thriving: What do survivors of gynecologic cancer want?

The purpose of this study was to characterize survivorship concerns and survivorship program preferences among gynecologic cancer survivors. Women treated for gynecologic malignancy at our cancer center were surveyed from 1/2019 to 10/2020 on concerns and preferences using a 5-point Likert scale. Descriptive analysis and multivariable logistic regression were performed to describe survivors' concerns/preferences. The most frequent survivorship concerns were fear of cancer recurrence (49.6%), desire to lose weight (40.0%), and long-term side effects (30.7%). The highest ranked survivorship program components included assistance with nutrition (36.5%), weight loss (30.4%), and stress reduction (29.0%). Older patients (≥64 y) were less likely to report concern with losing weight (OR 0.26, p < 0.05), sex life (OR 0.18, p < 0.01), and strain in family relationships (OR 0.27, p < 0.05) compared with younger patients. Compared with ovarian/fallopian tube/primary peritoneal cancer survivors, endometrial cancer survivors were less likely to desire nutritional education (OR 0.06, p < 0.01). Participants with advanced cancer were less likely to desire assistance with weight loss than those with early stage cancer (OR 0.23, p < 0.05). A significant portion of gynecologic cancer survivors reported a fear of cancer recurrence. Assistance with nutrition and weight loss were the most desired survivorship program components. Variation in patient preferences and differences among clinical subgroups highlight the need for tailored survivorship care.

Lessons learned: Telemedicine patterns and clinical application in patients with gynecologic cancers during COVID-19.

Objective: To describe the use of telemedicine in gynecologic oncology and identify patient characteristics associated with telemedicine use during COVID-19. Methods: Single-institution retrospective chart review of patients with gynecologic cancer who participated in in-person and telemedicine visits (video and telephone) from January 2019 to November 2020. Patient characteristics, visit and treatment characteristics were collected. Comparisons between 2019 and 2020 and between in-person and telemedicine visits were performed. Cancer-specific visit details were described. Results: From January to November 2020, 2,039 patients attended 5240 ambulatory visits in our gynecologic oncology outpatient clinics with 4,304 (82.1%) in-person visits, 512 (9.8%) video telemedicine visits, and 424 (8.1%) telephone visits. In 2020, 936 (45.9%) patients participated in a telemedicine visit. Demographic characteristics did not differ between those who participated in any telemedicine versus in-person visits (p > 0.05). Black patients represented a larger share of telephone visits but this was not significant. Patients aged > 65 years were more likely to use the telephone for a visit and less likely to use video visits compared to their younger counterparts. The majority of patients who attended a telemedicine visit also attended a visit in-person (88.0%). The most common purpose of the telemedicine visits was to discuss results and/or treatment plans (46%) with other appointments occurring for treatment check-ins and clinical trials. Conclusions: The use of telemedicine drastically increased in 2020. Patient demographics were not different between in-person and telemedicine visits except that older patients were more likely to use telephone visits over video visits. Telemedicine can be used for a variety of care needs in gynecologic oncology but further work needs to be done to optimize implementation, assess cost-effectiveness and patient outcomes.

A look at the gynecologic oncologist workforce - Are we meeting patient demand?

OBJECTIVE: to examine the geographic distribution of gynecologic oncologists (GO) and assess if the GO workforce is meeting the demand for oncology services for patients with gynecologic cancers. METHODS: We identified GO by National Provider Identifiers (NPI) and calculated county-level density of GO. County-level gynecologic cancer rates were derived from the U.S. Cancer Statistics to represent demand for GO services. A spatial data plot compared GO workforce to gynecologic cancer service demand. U.S. census county-level demographic information was collected and compared. RESULTS: In 2019, 1527 GO had a registered NPI. Of 3142 counties in the US, 2864 (91.2%) counties had no GO in their local county and 1943 (61.8%) counties had no GO in local or adjacent (neighboring) counties. As the gynecologic cancer rate increases (described in quintiles) in counties, there are fewer counties without a GO or adjacent GO. However, county-level GO density (number of GO per 100,000 women) did not significantly increase as the county-level incidence of gynecologic cancer increased (r = -0.12, p = 0.06)… Women living in counties with the highest gynecologic cancer rates and without access to a GO were more likely to reside in a rural area where residents had a lower median income and were predominately of White race.. CONCLUSION: There are a significant number of counties in the U.S. without a GO. As county-level gynecologic cancer incidence increased, the proportion of counties without a GO decreased; GO density did not increase with increasing cancer rates. Rural counties with high gynecologic incidence rates are underserved by GO. This information can inform initiatives to improve outreach and collaboration to better meet the needs of patients in different geographic areas.

Pembrolizumab and lenvatinib versus carboplatin and paclitaxel as first-line therapy for advanced or recurrent endometrial cancer: A Markov analysis.

OBJECTIVE: To determine the cost effectiveness of pembrolizumab/lenvatinib (P/L) versus standard-of-care carboplatin/paclitaxel (C/T) as first-line systemic therapy for patients with advanced/recurrent endometrial cancer. METHODS: We designed a Markov model to simulate treatment outcomes for advanced/recurrent endometrial cancer patients whose tumors are either microsatellite stable (MSS) or have high microsatellite instability (MSI-high). We adopted a healthcare sector perspective for the analysis. Model inputs for costs, health utility, and clinical estimates were obtained from the literature including data from GOG0209 and KEYNOTE-146. Primary outcomes included costs of care, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER). The time-horizon was three years and the discount rate was 3% annually. RESULTS: In a MSS cohort, compared to C/T, first-line treatment with P/L increased treatment costs by $212,670 and decreased QALYs by 0.28 per patient. In a MSI-high cohort, compared to C/T, P/L increased costs by $313,487 and increased QALYs by 0.11 per patient, representing an ICER of $2,849,882 per QALY. Sensitivity analyses found that the price of the new drugs was the most important determinant of the ICER and that the price of the new drugs would need to decrease by 85% to $2817 per cycle to reach a $150,000/QALY threshold. CONCLUSION: In the MSS model, we found that first-line therapy for advanced or recurrent endometrial cancer with P/L increased costs and worsened outcomes compared to C/T. In the MSI-high model, P/L improved survival and QALYs compared to C/T but was not cost-effective at the current cost of the drugs.

Postoperative complications of epidural analgesia at hysterectomy for gynecologic malignancies: an analysis of the National Surgical Quality Improvement Program.

OBJECTIVE: The aim of this study was to identify the rate of 30-day postoperative complications after the use of epidural in women undergoing hysterectomy for gynecologic malignancy. Secondary outcome was the impact of epidural on hospital length of stay. METHODS: A retrospective cohort study was conducted using the American College of Surgeons' National Surgical Quality Improvement Program database. This large dataset includes perioperative risk factors and 30-day post-operative outcomes from more than 680 hospitals. Women who underwent abdominal hysterectomy for a gynecologic malignancy from January 2014 to December 2017 were included. Adult patients (18 years or older) who underwent abdominal hysterectomy were identified using common procedure terminology and international classification of diseases codes. Only laparotomy cases were included, and minimally invasive cases (laparoscopy, transvaginal) were excluded due to the small prevalence of epidural cases in this cohort. All patients received general anesthesia. If patients were noted to have "epidural anesthesia" they were included in the epidural cohort and those receiving other adjuvant techniques (regional blocks or spinal anesthesia) were excluded. The primary outcome of interest was the 30-day occurrence of a pulmonary embolism, deep-vein thrombosis, pneumonia, and urinary tract infection. Those who received epidural analgesia were matched in a 1:1 ratio with a similar group of patients who did not receive epidural analgesia using a calculated propensity score to control for confounding factors. RESULTS: A total of 2035 (13.8%) patients undergoing abdominal hysterectomy for a gynecologic malignancy received epidural analgesia. 1:1 propensity-matched samples included 2035 patients in both epidural and no-epidural groups. Patient characteristics between groups were similar. Overall 30-day complication rates were higher in the epidural group (75.9% vs 62.0%, P<0.01). Specific complications that were higher in the epidural group included: blood transfusion (28.9% vs 22.8%); wound disruption (2.0% vs 1.1%); surgical site infection (10.1% vs 7.2%); and delay in return of bowel function (12.3% vs 9.3%) (all P<0.05). Hospital length of stay was significantly longer in the epidural group as compared with the no-epidural group (5.69 days vs 4.79 days, P<0.01) and readmissions were higher in the epidural group (10.5% vs 9.7%, P<0.01), but there was no difference in 30-day mortality between the groups (P=0.62). DISCUSSION: The rate of 30-day complications and length of stay among women undergoing an abdominal hysterectomy for gynecologic malignancy was higher for those who received epidural analgesia, but there was no difference in 30-day mortality. Although epidural analgesia can provide a number of benefits when used for postoperative pain control, the possible association with increased 30-day morbidity and length of stay needs to be considered.

Pancreaticobiliary metastasis presenting as primary mucinous ovarian neoplasm: A systematic literature review.

True primary mucinous ovarian carcinomas are rarer than originally thought and their clinical behavior and treatment response are different than more common epithelial ovarian carcinomas. Secondary ovarian neoplasms often mimic the clinical and histological features of mucinous ovarian cancer making their diagnosis, and therefore treatment, more difficult. Misdiagnosis can have a significant impact on both treatment and prognosis. The majority of these secondary ovarian neoplasms arise from the gastrointestinal tract, with mucinous histology often of pancreaticobiliary origin. Our study objective was to review current evidence distinguishing pancreaticobiliary ovarian metastasis from primary mucinous ovarian carcinoma. We utilized a PubMed search using MeSH terms and selected articles were reviewed, synthesized and summarized. Thirty-nine articles were included in the review. The clinical, gross, histological and immunohistochemical features distinguishing primary mucinous ovarian carcinomas from pancreaticobiliary ovarian metastasis were identified. Compared to primary mucinous ovarian carcinoma, metastatic pancreaticobiliary tumors are more often bilateral, <10 cm, have irregular external surface and surface implants, display an infiltrative pattern of invasion and stain for MUC1 and CK17. Primary ovarian mucinous tumors rarely (<3%) have signet ring cells or involvement of the hilum. Metastatic mucinous tumors mimic their primary mucinous ovarian counterparts and their clinical and histopathological features overlap in many ways. However, these metastatic tumors have features that can help differentiate them from primary mucinous carcinoma. With a high index of suspicion and knowledge of the reviewed features, distinguishing these tumors will continue to become easier.

A preoperative risk score to predict red blood cell transfusion in patients undergoing hysterectomy for ovarian cancer.

BACKGROUND: Patients with ovarian cancer experience a high rate of anemia throughout their treatment course, with rates that range from 19-95%. Blood transfusions offer symptom relief but may be costly, are limited in supply, and have been associated with worse 30-day surgical morbidity and mortality rates. OBJECTIVE: The purpose of this study was to identify risk factors for blood transfusion with packed red blood cell and to develop a transfusion risk score to identify patients who undergo surgery for ovarian cancer and who are at lowest risk for a blood transfusion. Our aim was to help clinicians identify those patients who may not require a crossmatch to encourage resource use and cost-savings. STUDY DESIGN: This is a retrospective database cohort study of 3470 patients who underwent hysterectomy for ovarian cancer with the use the National Surgical Quality Improvement Program database from 2014-2016. The association between risk factors with respect to 30-day postoperative blood transfusion was modeled with the use of logistic regression. A risk score to predict blood transfusion was created. RESULTS: Eight hundred ninety-one (25.7%) patients received a blood transfusion. In multivariate analysis, blood transfusion was associated independently with age (odds ratio, 1.90, P<.01), African American race (odds ratio, 2.30; P<.01), ascites (odds ratio, 1.89; P=.02), preoperative hematocrit level <30% (odds ratio, 10.70; P<.01), preoperative platelet count >400×109/L (odds ratio, 1.75; P<.01), occurrence of disseminated cancer (odds ratio, 1.71; P<.01), open surgical approach (odds ratio, 7.88; P<.01), operative time >3 hours (odds ratio, 2.19; P<.01), and additional surgical procedures that included large bowel resection (odds ratio, 4.23; P<.01), bladder/ureter resection (odds ratio, 1.69; P=.02), and pelvic exenteration (P=.02). A preoperative risk score that used age, race, ascites, preoperative hematocrit level, platelets, presence of disseminated cancer, planned hysterectomy approach, and procedures accurately predicted blood transfusion with good discriminatory ability (C-statistic=0.80 [P<.001]; C-statistic=0.69 [P<.001] for derivation and validation datasets, respectively) and calibration (Hosmer-Lemeshow goodness-of-fit, P=.081; P=.56 for derivation and validation datasets, respectively). CONCLUSION: Patients who undergo hysterectomy for ovarian cancer experience a high incidence of blood transfusions in the perioperative period. Preoperative risk factors and planned surgical procedures can be used in our transfusion risk score to help predict anticipated blood requirements.

Food Insecurity, Food "Deserts," and Glycemic Control in Patients With Diabetes: A Longitudinal Analysis.

OBJECTIVE: Both food insecurity (limited food access owing to cost) and living in areas with low physical access to nutritious foods are public health concerns, but their relative contribution to diabetes management is poorly understood. RESEARCH DESIGN AND METHODS: This was a prospective cohort study. A random sample of patients with diabetes in a primary care network completed food insecurity assessment in 2013. Low physical food access at the census tract level was defined as no supermarket within 1 mile in urban areas and 10 miles in rural areas. HbA1c measurements were obtained from electronic health records through November 2016. The relationship among food insecurity, low physical food access, and glycemic control (as defined by HbA1c) was analyzed using hierarchical linear mixed models. RESULTS: Three hundred and ninety-one participants were followed for a mean of 37 months. Twenty percent of respondents reported food insecurity, and 31% resided in an area of low physical food access. In adjusted models, food insecurity was associated with higher HbA1c (difference of 0.6% [6.6 mmol/mol], 95% CI 0.4-0.8 [4.4-8.7], P < 0.0001), which did not improve over time (P = 0.50). Living in an area with low physical food access was not associated with a difference in HbA1c (difference 0.2% [2.2 mmol/mol], 95% CI -0.2 to 0.5 [-2.2 to 5.6], P = 0.33) or with change over time (P = 0.07). CONCLUSIONS: Food insecurity is associated with higher HbA1c, but living in an area with low physical food access is not. Food insecurity screening and interventions may help improve glycemic control for vulnerable patients.

Interval robotic cytoreduction following neoadjuvant chemotherapy in advanced ovarian cancer.

The objective of this study is to review our experience with robotic interval cytoreduction following neoadjuvant chemotherapy for advanced ovarian cancer. We retrospectively reviewed patients with advanced ovarian cancer treated with neoadjuvant chemotherapy (NAC) and interval robotic cytoreduction (IRC) between 2011 and 2016 at the University of Rochester Medical Center. Demographic information, chemotherapy treatment, operative results, and follow-up were extracted from medical records. Twenty-nine patients underwent IRC after a mean of 3.9 cycles of NAC. The mean operative time was 165 min with a mean EBL of 107 cc. The mean length of stay was 2.0 days. One case (3.3%) was converted to an open procedure because of extensive tumor not amenable to robotic cytoreduction. Overall, 19 (66%) patients underwent an R0 cytoreduction, 8 (28%) an optimal (<1 cm) cytoreduction, and 2 (7%) a suboptimal cytoreduction. The median overall survival was 39.7 months and median progression-free survival was 21.2 months. Interval robotic cytoreduction following NAC is feasible and may be preferable to open interval cytoreductive surgery, in specific patients, to minimize morbidity and length of hospital stay.

Effectiveness of diabetes interventions in the patient-centered medical home.

The patient-centered medical home (PCMH) is an innovative care model for the provision of primary care that is being rapidly adopted in the U.S. with the support of federal agencies and professional organizations. Its goal is to provide comprehensive, patient-centered care with increased access, quality, and efficiency. Diabetes, as a common, costly, chronic disease that requires ongoing management by patients and providers, is a condition that is frequently monitored as a test case in PCMH implementations. While in theory a PCMH care model that supports patient engagement and between-visit care may help improve diabetes care delivery and outcomes, the success of this approach may depend largely upon the specific strategies used and implementation approach. The cost-effectiveness of diabetes care in the PCMH model is not yet clear. Interventions have been most effective and most cost-effective for those with the poorest diabetes management at baseline.

Analysis of Ca2+ signaling motifs that regulate proton signaling through the Na+/H+ exchanger NHX-7 during a rhythmic behavior in Caenorhabditis elegans.

Membrane proton transporters contribute to pH homeostasis but have also been shown to transmit information between cells in close proximity through regulated proton secretion. For example, the nematode intestinal Na(+)/H(+) exchanger NHX-7 causes adjacent muscle cells to contract by transiently acidifying the extracellular space between the intestine and muscle. NHX-7 operates during a Ca(2+)-dependent rhythmic behavior and contains several conserved motifs for regulation by Ca(2+) input, including motifs for calmodulin and phosphatidylinositol 4,5-bisphosphate binding, protein kinase C- and calmodulin-dependent protein kinase type II phosphorylation, and a binding site for calcineurin homologous protein. Here, we tested the idea that Ca(2+) input differentiates proton signaling from pH housekeeping activity. Each of these motifs was mutated, and their contribution to NHX-7 function was assessed. These functions included pH recovery from acidification in cells in culture expressing recombinant NHX-7, extracellular acidification measured during behavior in live moving worms, and muscle contraction strength as a result of this acidification. Our data suggest that multiple levels of Ca(2+) input regulate NHX-7, whose transport capacity normally exceeds the minimum necessary to cause muscle contraction. Furthermore, extracellular acidification limits NHX-7 proton transport through feedback inhibition, likely to prevent metabolic acidosis from occurring. Our findings are consistent with an integrated network whereby both Ca(2+) and pH contribute to proton signaling. Finally, our results obtained by expressing rat NHE1 in Caenorhabditis elegans suggest that a conserved mechanism of regulation may contribute to cell-cell communication or proton signaling by Na(+)/H(+) exchangers in mammals.