Christopher M. Tarney

A clinicopathologic study of vaginal intraepithelial neoplasia.

OBJECTIVE: To evaluate the natural history of vaginal intraepithelial neoplasia (VAIN) and to identify risk factors for invasive vaginal carcinoma. METHODS: The records of all women with VAIN diagnosed at military treatment facilities over a 10-year period with minimum follow-up of 12 months were reviewed. Patient demographics and clinical information related to the diagnosis and treatment of VAIN were recorded. RESULTS: One hundred twenty-seven women with VAIN met inclusion criteria. The mean age was 47.4 years, and median surveillance was 34 months (range 12–169 months). Seventy-five patients had low-grade vaginal dysplasia as their initial diagnosis, and 15 (20%) of these patients underwent treatment. Fifty-two patients had high-grade vaginal dysplasia, of which 38 (73%) underwent treatment. Overall, 113 patients (89%) demonstrated normalization of disease, 11 patients (9%) demonstrated persistence of disease, and three patients (2%) experienced recurrence of disease. No patients experienced development of invasive vaginal carcinoma. However, median time to normalization was 6 months longer in patients with low-grade dysplasia compared with those with high-grade dysplasia (15.9 months compared with 10.0 months; hazard ratio 1.5; 95% confidence interval 1.004–2.1; P=.045). Patients with high-grade dysplasia had more biopsies performed during their surveillance than patients with low-grade dysplasia (3.3 compared with 2.5; P=.045). CONCLUSION: Overall, 89% of patients demonstrated normalization of VAIN, and none had progression to invasive cancer. Normalization, persistence, and recurrence rates did not significantly differ by grade of dysplasia or treatment status. Based on our findings regarding the time to normalization, annual surveillance with combined cytology and colposcopy is likely adequate. Because 11% of patients with VAIN either will experience recurrence or will have persistent disease, lifetime surveillance is recommended. LEVEL OF EVIDENCE: III

Bladder Injury During Cesarean Delivery

Cesarean section is the most common surgery performed in the United States with over 30% of deliveries occurring via this route. This number is likely to increase given decreasing rates of vaginal birth after cesarean section (VBAC) and primary cesarean delivery on maternal request, which carries the inherent risk for intraoperative complications. Urologic injury is the most common injury at the time of either obstetric or gynecologic surgery, with the bladder being the most frequent organ damaged. Risk factors for bladder injury during cesarean section include previous cesarean delivery, adhesions, emergent cesarean delivery, and cesarean section performed at the time of the second stage of labor. Fortunately, most bladder injuries are recognized at the time of surgery, which is important, as quick recognition and repair are associated with a significant reduction in patient mortality. Although cesarean delivery is a cornerstone of obstetrics, there is a paucity of data in the literature either supporting or refuting specific techniques that are performed today. There is evidence to support double-layer closure of the hysterotomy, the routine use of adhesive barriers, and performing a Pfannenstiel skin incision versus a vertical midline subumbilical incision to decrease the risk for bladder injury during cesarean section. There is also no evidence that supports the creation of a bladder flap, although routinely performed during cesarean section, as a method to reduce the risk of bladder injury. Finally, more research is needed to determine if indwelling catheterization, exteriorization of the uterus, and methods to extend hysterotomy incision lead to bladder injury.

Rupture of an unscarred uterus in a quadruplet pregnancy.

BACKGROUND: Uterine rupture of an unscarred uterus is a rare complication in a quadruplet pregnancy. CASE: A 30-year-old woman, gravida 4 para 0030, with a quadruplet pregnancy and no previous uterine surgeries presented with moderate vaginal bleeding at 32 4/7 weeks of gestation. Fetal testing was reassuring, and the cervix showed no signs of preterm labor. A decision was made to proceed with cesarean delivery because of the amount of vaginal bleeding, with surgical findings of uterine rupture superior to the lower uterine segment. CONCLUSION: High-order gestations may be an independent risk factor for uterine rupture.

Prevalence of Human Papillomavirus in Self-Collected Cervicovaginal Swabs in Young Women in the United States Between 2003 and 2012.

OBJECTIVE: To evaluate whether there was a change in prevalence of human papillomavirus (HPV) in the United States correlated with the introduction of HPV vaccines in both vaccinated and unvaccinated women. METHODS: We performed a retrospective review of prevalence data for women aged 18–29 years living in the United States using the National Health and Nutrition Examination Surveys, which is an ongoing series of cross-sectional surveys. Participants provided responses to standardized questions and self-collected cervicovaginal swabs in which a Linear Array HPV Assay was used to determine HPV prevalence. A total of 783 women from the prevaccine era (2003–2004) and 1,526 from the postvaccine era (2007–2012) were analyzed. RESULTS: Among women aged 18–29 years, the prevalence of vaccine-type HPV declined among women receiving one or more doses of vaccine (P=.003): 10.1% (95% confidence interval [CI] 7.1–13.8%) in the prevaccine era to 4.2% (95% CI 3.3–10.9%) in the postvaccine era. There was no change in prevalence of nonvaccine-type HPV among women receiving one or more doses of vaccine (P>.05). There was also no change in prevalence of vaccine-type HPV among unvaccinated women from the prevaccine era 10.1% (95% CI 7.1–13.8%) to 8.8% (95% CI 5.6–12.9%) in the postvaccine era (P=.4). Vaccine coverage increased to 31.5% of eligible women aged 18–29 years as of 2011–2012. CONCLUSION: Six years after introduction of HPV vaccination in the United States, there has been a decrease in the prevalence of vaccine-type HPV among women correlated with receiving one or more vaccine doses with no change in nonvaccine-type HPV. Furthermore, there has been no change in prevalence of vaccine-type HPV among unvaccinated women.

Association of Spouse Deployment on Pregnancy Outcomes in a U.S. Military Population.

OBJECTIVE: To evaluate the association of spousal deployment during the antenatal period on maternal and neonatal outcomes and to estimate whether group prenatal care may be beneficial in reducing adverse outcomes when spouses are deployed. METHODS: Primigravid women who delivered at Womack Army Medical Center, Fort Bragg, North Carolina, were prospectively enrolled and selected for participation on a random basis between January 2013 and January 2014. Women whose spouses were deployed to a combat zone during the entire pregnancy (deployed group) were compared with women whose spouses were not deployed during the pregnancy (nondeployed group). Pregnancy and neonatal outcomes were compared between groups. RESULTS: Three hundred ninety-seven women were enrolled with 183 (46.1%) in the deployed group and 214 (53.9%) in the nondeployed group. Spouse deployment was associated with increased risk of preterm delivery (38 [20.8%] compared with 16 [7.5%], P<.001) and postpartum depression (30 [16.4%] compared with 13 [6.1%], P=.001) when compared with women in the nondeployed group. There were no differences in the incidence of preterm delivery and postpartum depression for women in the deployed group who participated in group prenatal care when compared with women participating in traditional care (preterm delivery 6 [14.6%] compared with 32 [22.5%], P=.38; postpartum depression 4 [9.8%] compared with 26 [18.3%], P=.24). CONCLUSION: Women who have a spouse deployed during their pregnancy are at increased risk for preterm birth and postpartum depression. Larger studies are needed to evaluate whether spouse deployment during pregnancy has other perinatal effects and whether group prenatal care may have a positive effect on adverse perinatal outcomes in this population. LEVEL OF EVIDENCE: II

Racial disparities in molecular subtypes of endometrial cancer

OBJECTIVES Racial differences in the molecular subtypes of endometrial cancer and associations with progression-free survival (PFS) were evaluated. METHODS Molecular, clinical and PFS data were acquired from the Cancer Genome Atlas (TCGA) including classification into the integrative, somatic copy number alteration and transcript-based subtypes. The prevalence and prognostic value of the aggressive molecular subtypes (copy number variant [CNV]-high, cluster 4 or mitotic) were evaluated in Black and White patients. RESULTS There were 337 patients including 14% self-designated as Black, 27% with advanced stage, and 82% with endometrioid histology. The CNV-high subtype was more common in Black than White patients (61.9% vs. 23.5%, P=0.0005) and suggested worse PFS in Black patients (hazard ratio [HR]=3.4, P=0.189). The cluster 4 subtype was more prevalent in Black patients (56.8% vs. 20.9%, P<0.0001) and associated with worse PFS in Black patients (HR=3.4, P=0.049). The mitotic subtype was more abundant in Black patients (64.1% vs. 33.7%, P=0.002), indicated worse PFS in Black patients (HR=4.1, P=0.044) including the endometrioid histology (HR=6.1, P=0.024) and exhibited race-associated enrichment in cell cycle signaling and pathways in cancer including PLK1 and BIRC7. All of these aggressive molecular subtypes also indicated worse PFS in White patients, with unique enrichments in mitotic signaling different from Black patients. CONCLUSIONS The aggressive molecular subtypes from TCGA were more common in Black endometrial cancer patients and indicated worse PFS in both Black and White patients. The mitotic subtypes also indicated worse PFS in Black patients with endometrioid histology. Enrichment patterns in mitotic signaling may represent therapeutic opportunities.

Impact of age at diagnosis on racial disparities in endometrial cancer patients

INTRODUCTION Although black patients with endometrial cancer (EC) have worse survival compared with white patients, the interaction between age/race has not been examined. The primary objective was to evaluate the impact of age at diagnosis on racial disparities in disease presentation and outcome in EC. METHODS We evaluated women diagnosed with EC between 1991 and 2010 from the Surveillance, Epidemiology, and End Results. Mutation status for TP53 or PTEN, or with the aggressive integrative, transcript-based, or somatic copy number alteration-based molecular subtype were acquired from the Cancer Genome Atlas. Logistic regression model was used to estimate the interaction between age and race on histology. Cox regression model was used to estimate the interaction between age and race on survival. RESULTS 78,184 white and 8518 black patients with EC were analyzed. Median age at diagnosis was 3-years younger for black vs. white patients with serous cancer and carcinosarcoma (P<0.0001). The increased presentation of non-endometrioid histology with age was larger in black vs. white patients (P<0.0001). The racial disparity in survival and cancer-related mortality was more prevalent in black vs. white patients, and in younger vs. older patients (P<0.0001). Mutations in TP53, PTEN and the three aggressive molecular subtypes each varied by race, age and histology. CONCLUSIONS Aggressive histology and molecular features were more common in black patients and older age, with greater impact of age on poor tumor characteristics in black vs. white patients. Racial disparities in outcome were larger in younger patients. Intervention at early ages may mitigate racial disparities in EC.

HPV Vaccination Does Not Provide Herd Immunity for Unvaccinated Women or Cross-Protection for Nonvaccine HPV Types [12].

INTRODUCTION: To determine if the human papillomavirus (HPV) vaccination offers cross-protection against nonvaccine HPV types and whether introduction of the vaccination has offered herd immunity to unvaccinated women. METHODS: We collected and analyzed HPV prevalence data for females aged 18–29 from the prevaccine era (2007–2008) and postvaccine era (2009–2012) using the National Health and Nutrition Examination Surveys (NHANES); 1628 female respondents aged 18–29, representing 21,135,134 females in the United States non-institutionalized civilian population, provided vaginal swabs across three consecutive NHANES survey cycles. RESULTS: Among females aged 18–29, the prevalence of high risk HPV among women who received at least one dose of the HPV vaccine decreased from 67% (95% confidence interval [CI] 50.7–81.4) in 2007–2008 to 41.5% (95% CI, 30.5–53.1) in 2011–2012; among the women vaccinated for HPV in the postvaccine era, the prevalence of HPV-16 and -18 was 6.4% versus 93.6% for all other high risk HPV types. There was no difference in prevalence in high risk HPV for women who did not receive the vaccine; 49.5% (95% CI, 42.5–56.6) in 2007–2008 versus 50.8% (95% CI, 43.0–58.7) in 2011–2012. CONCLUSION/IMPLICATIONS: The prevalence of high risk HPV significantly decreased among females aged 18–29 years who received the HPV vaccine, but there appeared to be no cross-protection against nonvaccine HPV types. These findings may offer support for usage of the investigational 9-valent HPV vaccine. There also was no evidence to suggest protection against HPV infection for unvaccinated women.

Cogan syndrome in pregnancy.

BACKGROUND: Cogan syndrome is a rare, multisystem, autoimmune disorder of unknown etiology. Little is known about whether it affects pregnancy or whether pregnancy affects the disease. CASE: A 24-year-old primigravid woman with Cogan syndrome diagnosed 3 years before her pregnancy presented to our clinic for prenatal care. During pregnancy she experienced no worsening of symptoms of her disease but reported subjective improvement in vision and hearing. Cesarean delivery was performed at term because of nonreassuring fetal status. There were no obstetric or postpartum complications. CONCLUSION: Cogan syndrome requires close monitoring. If it worsens, then the disease process can be similar to both physiologic and pathologic changes of pregnancy. However, unlike the former, worsening Cogan syndrome can have irreversible maternal consequences.

Transabdominal Ultrasonography to Detect Ureteral Patency in the Operative Suite

INTRODUCTION: The objective of this study was to compare ultrasound detection of ureteral jets with cystoscopy in verifying ureteral patency after gynecologic surgery in the operating suite. METHODS: Twenty women scheduled for gynecologic surgery whose surgeons routinely perform cystoscopy postoperatively were recruited for this study. At the conclusion of the case, transabdominal color Doppler ultrasonography was used intraoperatively to detect bilateral ureteral jets. After ultrasonography, cystoscopy was completed by the surgeon to detect ureteral patency. The timing to complete cystoscopy also was compared with the timing to perform the ultrasound scan. Statistical analysis was performed using the Students t test to determine significance between times to complete cystoscopy compared with ultrasonography. RESULTS: Bilateral ureteral jets were detected in all women with the use of both transabdominal color Doppler ultrasonography and cystoscopy. Time to detection of both ureteral jets was faster with the use of ultrasonography compared with cystoscopy (mean 72.2 seconds, standard deviation 43.8 seconds compared with mean 176.8 seconds, standard deviation 71.8 seconds]. CONCLUSION: Transabdominal color Doppler ultrasonography is a reasonable alternative to cystoscopy to document ureteral patency in the operative suite at the conclusion of gynecologic surgery. Larger studies are needed to determine whether ultrasonography is as effective as cystoscopy in screening for ureteral injury.