Use of endoscopic plication to repair a dysfunctional gastric conduit.

Video 1Full length video showing the use of endoscopic plication to repair a dysfunctional gastric conduit.

Association of Intrauterine Device Malposition With Previous Cesarean Delivery and Related Uterine Anatomical Changes.

OBJECTIVES: We sought to determine the association between intrauterine device (IUD) malposition and previous cesarean delivery (CD) and related uterine anatomical changes. METHODS: A retrospective cohort of all persons with an IUD presenting for two- and three-dimensional pelvic ultrasonography over 2 years, for any gynecologic indication, was compiled. IUD malposition was defined as IUD partially or completely positioned outside the endometrial cavity. Uterine position, uterine flexion, and cesarean scar defect (CSD) size were assessed. Patient characteristics and sonographic findings were compared between those with normally positioned and malpositioned IUD. Primary outcome was the rate of IUD malposition in persons with and without a history of CD. Logistic regression analysis was used to control for potential confounders. RESULTS: Two hundred ninety-six persons with an IUD had a pelvic ultrasound, 240 (81.1%) had a normally positioned IUD, and 56 (18.9%) had a malpositioned IUD. The most common location of IUD malposition was low uterine segment and cervix (67.9%). Malpositioned IUD was associated with referral for evaluation of pelvic pain (P = .001). Prior CD was significantly associated with a malpositioned IUD, after adjusting for confounders (aOR 3.50, 95% CI 1.31-9.35, P = .01). Among persons with prior CD, uterine retroflexion and a large CSD were independent risk factors for IUD malposition (aOR 4.1, 95% CI 1.1-15.9, P = .04 and aOR 5.4, 95% CI 1.4-20.9, P = .01, respectively). CONCLUSIONS: Prior CD is associated with significantly increased risk of IUD malposition. Among persons with previous CD, those with a retroflexed uterus and a large CSD are more likely to have a malpositioned IUD.

Cancer-Immunity Marker RNA Expression Levels across Gynecologic Cancers: Implications for Immunotherapy.

Our objective was to characterize cancer-immunity marker expression in gynecologic cancers and compare immune landscapes between gynecologic tumor subtypes and with nongynecologic solid tumors. RNA expression levels of 51 cancer-immunity markers were analyzed in patients with gynecologic cancers versus nongynecologic cancers, and normalized to a reference population of 735 control cancers, ranked from 0 to 100, and categorized as low (0-24), moderate (25-74), or high (75-100) percentile rank. Of the 72 patients studied, 43 (60%) had ovarian, 24 (33%) uterine, and 5 (7%) cervical cancer. No two immune profiles were identical according to expression rank (0-100) or rank level (low, moderate, or high). Patients with cervical cancer had significantly higher expression level ranks of immune activating, proinflammatory, tumor-infiltrating lymphocyte markers, and checkpoints than patients with uterine or ovarian cancer (P < 0.001 for all comparisons). However, there were no significant differences in immune marker expression between uterine and ovarian cancers. Tumors with PD-L1 tumor proportional score (TPS) ≥1% versus 0% had significantly higher expression levels of proinflammatory markers (58 vs. 49%, P = 0.0004). Compared to patients with nongynecologic cancers, more patients with gynecologic cancers express high levels of IDO-1 (44 vs. 13%, P < 0.001), LAG3 (35 vs. 21%, P = 0.008), and IL10 (31 vs. 15%, P = 0.002.) Patients with gynecologic cancers have complex and heterogeneous immune landscapes that are distinct from patient to patient and from other solid tumors. High levels of IDO1 and LAG3 suggest that clinical trials with IDO1 inhibitors or LAG3 inhibitors, respectively, may be warranted in gynecologic cancers.

Low grade appendiceal mucinous neoplasm metastatic to the ovary: A case report and intraoperative assessment guide.

INTRODUCTION: Incidence of low grade appendiceal mucinous neoplasm is increasing. Preoperatively, it may present similarly to primary ovarian malignancy. This case report describes a case of presumed ovarian malignancy with final pathologic diagnosis of low grade appendiceal mucinous neoplasm. We also propose several surgical strategies to approach this conundrum. PRESENTATION OF CASE: A postmenopausal woman with abdominal pain was found to have a 30 cm abdominopelvic mass with elevated CA-125 and CEA presumably a primary ovarian malignancy. During surgical staging, intraoperative findings were notable for an appendiceal mass. Intraoperative surgical oncology consultation recommended appendectomy for diagnostic purposes. Following primary surgery and final pathologic diagnosis, she underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. DISCUSSION: Low grade appendiceal mucinous neoplasm should be within the differential diagnosis of gynecologic surgeons when presented with a patient with large volume ascites and biopsy of acellular mucin. Intraoperatively, an abnormal appearing appendix with normal appearing gynecologic structures should trigger suspicion for appendiceal rather than ovarian origin. Preoperative symptoms, imaging studies, tumor markers, and frozen section pathology may not be able to differentiate between appendiceal and epithelial ovarian malignancies. CONCLUSION: A recognition of mucinous material and abnormal appearing appendix should prompt the surgeon to consider performing an appendectomy to obtain primary pathologic diagnosis. A high level of suspicion could better optimize the patient for a joint case with the appropriate surgeons. Given the documented disguise of low grade appendiceal mucinous neoplasm as primary ovarian cancer and its increasing incidence, diagnosis and general understanding of treatment should be understood.

Cancer immunity marker RNA expression levels across gynecologic cancers: Implications for immunotherapy.

Background: Our objective was to characterize cancer immunity marker expression in gynecologic cancers and compare immune landscapes between gynecologic tumor subtypes and with non-gynecologic solid tumors. Methods: RNA expression levels of 51 cancer-immunity markers were analyzed in patients with gynecologic cancers vs. non-gynecologic cancers, and normalized to a reference population of 735 control cancers, ranked from 0-100, and categorized as low (0-24), moderate (25-74), or high (75-100) percentile rank. Results: Of the 72 patients studied, 43 (60%) had ovarian, 24 (33%) uterine, and 5 (7%) cervical cancer. No two immune profiles were identical according to expression rank (0-100) or rank level (low, moderate, or high). Patients with cervical cancer had significantly higher expression level ranks of immune activating, pro-inflammatory, tumor infiltrating lymphocyte markers and checkpoints than patients with uterine or ovarian cancer (p<0.001 for all comparisons). However, there were no significant differences in immune marker expression between uterine and ovarian cancers. Tumors with PD-L1 TPS =>1% versus 0% had significantly higher expression levels of pro-inflammatory markers (58 vs. 49%, p=0.0004). Compared to patients with non-gynecologic cancers, more patients with gynecologic cancers express high levels of IDO-1 (44 vs. 13%, p<0.001), LAG3 (35 vs. 21%, p=0.008) and IL10 (31 vs. 15%, p=0.002.) Conclusions: Patients with gynecologic cancers have complex and heterogeneous immune landscapes that are distinct from patient to patient and from other solid tumors. High levels of IDO1 and LAG3 suggest that clinical trials with IDO1 inhibitors or LAG3 inhibitors, respectively, may be warranted in gynecologic cancers.

Increased Morbidity and Mortality in COVID-19 Patients with Liver Injury.

BACKGROUND: There is a high prevalence of liver injury (LI) in patients with coronavirus disease 2019 (COVID-19); however, few large-scale studies assessing risk factors and clinical outcomes in these patients have been done. AIMS: To evaluate the risk factors and clinical outcomes associated with LI in a large inpatient cohort of COVID-19 patients. METHODS: Adult patients with COVID-19 between March 1 and April 30, 2020, were included. LI was defined as peak levels of alanine aminotransferase/aspartate aminotransferase that were 3 times the ULN or peak levels in alkaline phosphatase/total bilirubin that were 2 times the ULN. Mild elevation in liver enzymes (MEL) was defined as abnormal peak liver enzyme levels lower than the threshold for LI. Patients with MEL and LI were compared to a control group comprising patients with normal liver enzymes throughout hospitalization. RESULTS: Of 1935 hospitalized COVID-19 patients, 1031 (53.2%) had MEL and 396 (20.5%) had LI. Compared to control patients, MEL and LI groups contained proportionately more men. Patients in the MEL cohort were older compared to control, and African-Americans were more highly represented in the LI group. Patients with LI had an increased risk of mortality (relative risk [RR] 4.26), intensive care unit admission (RR, 5.52), intubation (RR, 11.01), 30-day readmission (RR, 1.81), length of hospitalization, and intensive care unit stay (10.49 and 10.06 days, respectively) compared to control. CONCLUSION: Our study showed that patients with COVID-19 who presented with LI had a significantly increased risk of mortality and poor clinical outcomes.

Practice patterns and survival in FIGO 2009 stage 3B endometrial cancer.

OBJECTIVE: To describe the practice patterns and outcomes of patients with stage 3B endometrial cancer. METHODS: We queried the National Cancer Database for all surgically staged, stage 3 patients between 2012 and 2016. Patients who received any pre-operative therapy were excluded. Demographics, tumor factors, and adjuvant therapy for the stage 3 substages were compared. Logistic regression was used to identify factors associated with adjuvant therapy. Kaplan Meier curves were generated and compared using the log-rank test. Multivariable Cox Proportional Hazards Model was used to adjust for prognostic factors. Findings with p < 0.05 were considered significant. RESULTS: Of 7363 patients with stage 3 disease, 478 (6%) had stage 3B; 1732 (23%) had stage 3A, 3457 (48%) had stage 3C1, and 1696 (23%) had stage 3C2 disease. Post-surgical treatment consisted of: combined chemotherapy (CT) and radiation (RT) (49%), CT alone (28%), RT alone (9%), 14% received no postoperative therapy. Among all stage 3 substages, patients with stage 3B disease were the least likely to receive any CT, and the most likely to receive RT alone. After adjusting for known prognostic factors, patients with stage 3A (Hazard ratio (HR) of death = 0.64) and 3C1 (HR of death = 0.79) disease had significantly worse overall survival compared to stage 3B; survival was not demonstrably different from patients with stage 3C2 disease. Patients with stage 3B disease who received CT + RT had the best overall survival. CONCLUSION: Survival of patients with stage 3B disease is similar to that of patients with para-aortic node metastases and is inferior to all others with stage 3 endometrial cancer. Less frequent CT and a higher rate of post-operative RT alone, describes a distinct practice from that seen in other stage 3 patients.

Trends and geographic variation in women's representation as principal investigators (PI) in phase 3 gynecologic oncology clinical trials.

OBJECTIVE: To investigate the representation of women as principal investigators (PI) in phase 3, gynecologic oncology clinical trials. METHODS: ClinicalTrials.gov was queried for all phase 3 clinical trials with start dates between January 1, 2010 and December 31, 2020 using the search terms: "ovarian cancer", "endometrial cancer", and "cervical cancer". Trial characteristics were abstracted from the website. Gender of the PI was assessed by name, image on institutional website or by querying the trial coordinator. Trials were considered to have women's representation if women were the sole PI or among multiple co-PIs. Chi-square tests and relative risks were used to compare proportions across groups. Linear regression was used to assess trends over time. RESULTS: 200 unique clinical trials were included in this analysis, of which women were represented as PI in 76 (38%). Women were more likely to be a PI of trials funded by multiple sites than a single entity (RR = 1.80, 95% confidence interval (CI) 1.25, 2.61, p = 0.01), registered outside of Asia than those in Asia (RR = 1.78, 95% CI 1.11, 2.88, p = 0.02), and trials with multiple co-PIs than with one PI (RR = 1.78 (95% CI 1.18, 2.67), p = 0.01). Overall, women's representation as a PI increased by 3% annually (by year of registration, R2 = 0.61, p = 0.01). This increase was most evident in trials registered in multiple continents and Europe (both 4% annually). CONCLUSIONS: Women's representation as PIs in clinical trials has increased in the last decade. Trials funded by multiple sources outside of Asia have the highest proportion of PIs who are women. These trends may represent ongoing leadership and mentorship opportunities for women gynecologic oncologists.

Association of obesity with illness severity in hospitalized patients with COVID-19: A retrospective cohort study.

BACKGROUND: Although recent studies have shown an association between obesity and adverse coronavirus disease 2019 (COVID-19) patient outcomes, there is a paucity in large studies focusing on hospitalized patients. We aimed to analyze outcomes associated with obesity in a large cohort of hospitalized COVID-19 patients. METHODS: We performed a retrospective study at a tertiary care health system of adult patients with COVID-19 who were admitted between March 1 and April 30, 2020. Patients were stratified by body mass index (BMI) into obese (BMI ≥ 30 kg/m 2) and non-obese (BMI < 30 kg/m 2) cohorts. Primary outcomes were mortality, intensive care unit (ICU) admission, intubation, and 30-day readmission. RESULTS: A total of 1983 patients were included of whom 1031 (51.9%) had obesity and 952 (48.9%) did not have obesity. Patients with obesity were younger (P < 0.001), more likely to be female (P < 0.001) and African American (P < 0.001) compared to patients without obesity. Multivariable logistic models adjusting for differences in age, sex, race, medical comorbidities, and treatment modalities revealed no difference in 60-day mortality and 30-day readmission between obese and non-obese groups. In these models, patients with obesity had increased odds of ICU admission (adjusted OR, 1.37; 95% CI, 1.07-1.76; P = 0.012) and intubation (adjusted OR, 1.37; 95% CI, 1.04-1.80; P = 0.026). CONCLUSIONS: Obesity in patients with COVID-19 is independently associated with increased risk for ICU admission and intubation. Recognizing that obesity impacts morbidity in this manner is crucial for appropriate management of COVID-19 patients.

Assessment of malnutrition by unintentional weight loss and its implications on oncologic outcomes in patient with locally advanced cervical cancer receiving primary chemoradiation.

OBJECTIVES: To determine the prevalence, risk factors for, and clinical implications of unintentional weight loss on oncologic outcomes in locally advanced cervical cancer (LACC) treated with concurrent chemotherapy and contemporary radiation techniques. METHODS: This a single-institution, retrospective cohort study of patients with LACC who received definitive chemoradiation (CRT) from 2010 to 2015. Clinicopathologic factors were abstracted by chart review and characterized using descriptive statistics. Factors associated with severe weight loss (≥10% from baseline) were determined by Chi-square test. Time-to-event analysis was performed using the Kaplan Meier method and regression was performed using the Cox Proportional hazards model. RESULTS: One hundred and eight patients comprised the cohort. The majority of patients were White, obese, and had squamous histology. Almost 80% of patients experienced at least some weight loss, with 14% of patients experiencing severe weight loss. Patients with FIGO 2009 stage 3 or 4 disease had a 3.4-fold increased risk of severe weight loss compared to those with earlier stage disease. Patients who had severe weight loss had a higher risk for death (HR = 2.37, 95% confidence interval [CI] 1.77, 7.37, p = 0.036) and a trend toward high risk for recurrence (HR = 1.43, 95% CI 0.46, 3.32, p = 0.107) compared to patients without severe weight loss. CONCLUSION: Unintentional weight loss is a common symptom of patients with LACC receiving CRT that affects oncologic outcomes, yet it remains under-recognized. Increased awareness of weight loss and malnutrition may encourage interventions to improve this potentially modifiable risk factor for worse prognosis and quality of life.

Vaccine Strategies for Human Papillomavirus-Associated Head and Neck Cancers.

The rising incidence of oropharyngeal squamous cell cancers (OPSCC) in the United States is largely attributed to HPV. Prophylactic HPV vaccines have demonstrated effectiveness against oral infection of HPV 16 and HPV 18. We review the global epidemiology and biology of HPV-related cancers as well as the development of HPV vaccines and their use worldwide. We also review the various strategies and challenges in development of therapeutic HPV vaccines.

HIPEC after neoadjuvant chemotherapy and interval debulking is associated with development of platinum-refractory or -resistant disease.

OBJECTIVE: To describe our single-institution oncologic outcomes of patients who received neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: We compared clinicopathologic information and outcomes for all patients with advanced stage, high-grade serous ovarian cancer who received NACT and IDS with (N = 20) or without (N = 48) HIPEC at our institution from 2010 to 2019 RESULTS: Mean age (62 years with HIPEC and 60 years without HIPEC) and proportion of stage 4 disease (40% for both) did not differ between cohorts. HIPEC patients had higher rates of complete cytoreduction (95% vs 50%), longer mean duration of surgery (530 vs. 216 min), more grade 3 or 4 postoperative complications (65% vs. 4%), and longer mean length of hospital stay (8 vs. 5 days). HIPEC patients had significantly higher risk for platinum-refractory progression or platinum-resistance recurrence (50% vs 23%; RR = 2.18; 95% CI 1.11, 4.30, p = 0.024). Median progression free survival (11.5 vs. 12 months) and all-cause mortality (19.1 vs. 30.5 months) in the HIPEC and non-HIPEC cohorts, respectively, did not differ CONCLUSIONS: HIPEC was associated with increased risk for platinum refractory or resistant disease. Higher surgical complexity may contribute to higher complication rates without improving oncologic outcomes in our patients. Further investigations and long-term follow-up are needed to assess the utility of HIPEC in primary treatment of advanced stage ovarian cancer.

The Changing Landscape of Therapeutic Cancer Vaccines-Novel Platforms and Neoantigen Identification.

Therapeutic cancer vaccines, an exciting development in cancer immunotherapy, share the goal of creating and amplifying tumor-specific T-cell responses, but significant obstacles still remain to their success. Here, we briefly outline the principles underlying cancer vaccine therapy with a focus on novel vaccine platforms and antigens, underscoring the renewed optimism. Numerous strategies have been investigated to overcome immunosuppressive mechanisms of the tumor microenvironment (TME) and counteract tumor escape, including improving antigen selection, refining delivery platforms, and use of combination therapies. Several new cancer vaccine platforms and antigen targets are under development. In an effort to amplify tumor-specific T-cell responses, a heterologous prime-boost antigen delivery strategy is increasingly used for virus-based vaccines. Viruses have also been engineered to express targeted antigens and immunomodulatory molecules simultaneously, to favorably modify the TME. Nanoparticle systems have shown promise as delivery vectors for cancer vaccines in preclinical research. T-win is another platform targeting both tumor cells and the TME, using peptide-based vaccines that engage and activate T cells to target immunoregulatory molecules expressed on immunosuppressive and malignant cells. With the availability of next-generation sequencing, algorithms for neoantigen selection are emerging, and several bioinformatic platforms are available to select therapeutically relevant neoantigen targets for developing personalized therapies. However, more research is needed before the use of neoepitope prediction and personalized immunotherapy becomes commonplace. Taken together, the field of therapeutic cancer vaccines is fast evolving, with the promise of potential synergy with existing immunotherapies for long-term cancer treatment.

Charting a professional course for academic gynecologic oncology mentors.

OBJECTIVES: To describe the transition from a mentee to mentor role in a cohort of academic gynecologic oncologists by studying the evolution of authorship placement in peer reviewed publications by current gynecologic oncology (GO) fellowship directors. METHODS: Current GO fellowship directors were identified from the ACGME website. A Pubmed search identified all publications by all listed fellowship directors. Number of publications, and order of authorship were counted by years since medical school graduation. Milestones representing likely career transition points were developed and tracked. Descriptive statistics were used to characterize the individuals and associated institutions. Time to event curves were compared using the Kaplan Meier method. RESULTS: The study cohort comprised 58 GO fellowship program directors. The median time since medical school graduation was 22 years. Eight unique milestones reflecting the relative frequencies of authorship placement were studied. The median time to accomplishing these milestones ranged from 6 to 18 years. The timing of milestone attainment suggests a stepwise progression of events and was associated with both individual and institutional factors. CONCLUSIONS: In this cohort of 58 fellowship directors, a roadmap to mentorship was identified, that includes several measurable milestones, and representative times to attain each. Further analyses identified a set of factors associated with the rate of progression. We hope these findings can inform the evolution of mentorship in gynecologic oncology. It is possible that initiatives focused on mentorship training might include milestone tracking to facilitate development.

Current status of hyperthermic intraperitoneal chemotherapy (HIPEC) for ovarian cancer in the United States.

OBJECTIVES: 1.) To compare frequency of HIPEC use in ovarian cancer treatment before and after publication of the phase III study by van Driel et al. in January 2018. 2.) To compare associated rates of hospital-based outcomes, including length of stay, intensive care unit (ICU) admission, complications, and costs in ovarian cancer surgery with or without HIPEC. METHODS: We queried Vizient's administrative claims database of 550 US hospitals for ovarian cancer surgeries from January 2016-January 2020 using ICD-10 diagnosis and procedure codes. Sodium thiosulfate administration was used to identify HIPEC cases according to the published protocol. Student t-tests and relative risk (RR) were used to compare continuous variables and contingency tables, respectively. RESULTS: 152 ovarian cancer patients had HIPEC at 39 hospitals, and 20,014 ovarian cancer patients had surgery without HIPEC at 256 hospitals. Following the trial publication, 97% of HIPEC cases occurred. During the index admission, HIPEC patients had longer median length of stay (8.4 vs. 5.7 days, p < 0.001) and higher percentage of ICU admissions (63.1% vs. 11.0%, p < 0.001) and complication rates (RR = 1.87, p = 0.002). Index admission direct costs ($21,825 vs. $12,038, p < 0.001) and direct cost index (observed/expected costs) (1.87 vs. 1.11, p < 0.001) were also greater in the HIPEC patients. No inpatient deaths or 30-day readmissions were identified after HIPEC. CONCLUSIONS: Use of HIPEC for ovarian cancer increased in the US after publication of a phase III clinical trial in a high-impact journal, though the absolute number of cases remains modest. Incorporation of HIPEC was associated with increased cost, hospital length of stay, ICU admission, and hospital-acquired complication rates. Further studies are needed in order to evaluate long-term outcomes, including morbidity and survival.

Evaluating When and Why Patients Discontinue Chronic Therapy for Irritable Bowel Syndrome With Constipation and Chronic Idiopathic Constipation.

INTRODUCTION: To inform the patient-centered discussion regarding comparative outcomes with irritable bowel syndrome/chronic idiopathic constipation pharmacotherapy, we evaluated reasons and timing of discontinuation of FDA-approved pharmacotherapy for irritable bowel syndrome and chronic idiopathic constipation in a large observational real-world cohort. METHODS: We identified patients initiating lubiprostone or linaclotide within the University of Michigan Electronic Medical Record (2012-2016). Medication start and stop dates were determined in manual chart review including detailed review of all documentation including office notes and telephone encounters. A Cox model was constructed to predict the hazard of discontinuation. RESULTS: On multivariate analysis of 1,612 patients, linaclotide users had a lower risk of discontinuing therapy than lubiprostone users for any reason (hazard ratio [HR] = 0.6, 95% confidence interval [CI] 0.5-0.8). At 3 and 12 months, the overall discontinuation rates were 23% and 43% for lubiprostone compared with 14% and 24% for linaclotide. Over the first year of therapy, more than half of discontinuations due to intolerance occurred in the first 3 months for both drugs. Linaclotide users were more likely to discontinue due to intolerance (HR = 1.6 [95% CI, 1.2-2.3]) but less likely to discontinue due to insufficient efficacy of therapy (HR = 0.5 [95% CI, 0.4-0.8]). IBS diagnosis increased the hazard of discontinuation of lubiprostone relative to linactolide (HR = 1.4, 95% CI, 1.1-1.6). Loss of prescription drug coverage remained a common reason for discontinuation over the first year of therapy. DISCUSSION: Individuals appear more likely to discontinue lubiprostone than linaclotide overall, but more likely to discontinue linaclotide compared with lubiprostone due to intolerance (mostly diarrhea). Most discontinuations due to intolerance occur in the first 3 months. These results may be useful in individualized treatment selection and enhancing patient knowledge regarding long-term outcomes.