Recent Research Publications- August 2022
Superficial versus deep inguinal nodal dissection for vulvar cancer staging.
Mattson J, Emerson J, Underwood A, Sun G, Mott SL, Kulkarni A, Robison K,
Gynecol Oncol. 2022 Jun 30:S0090-8258(22)00428-0. doi: 10.1016/j.ygyno.2022.06.024. Epub ahead of print.
- The objective of this study was to compare the rate of groin recurrence among women undergoing superficial or deep inguinal lymph node dissections in suspected early-stage vulvar carcinoma. Secondary objectives included comparison of overall survival and post-operative morbidity between the study groups
- A retrospective cohort of 233 patients with squamous cell carcinoma (SCC) of the vulva who underwent an inguinal lymph node dissection at two major academic institutions from 1999 to 2017 were analyzed. Demographic, surgical, recurrence, survival, and post-operative morbidity data were collected for 233 patients, resulting in a total of 400 groin node dissections analyzed.
- Rates of overall primary recurrence of disease between superficial and deep inguinal LND (42.5 vs. 39.8%, p = 0.70) and rates of inguinal recurrence (3.4 vs. 8.3%, p = 0.16) were similar. Overall rates of postoperative morbidity were significantly higher in the cohort undergoing deep LND (70.3% vs 44.3%, p < 0.01). Rates of lymphedema (42.4 vs 15.9%, p < 0.01), readmission (26.3 vs 6.8%, p < 0.01), and infection (40.7 vs 14.8%, p < 0.01) were all significantly higher among patients undergoing deep LND. There was no significant difference noted in overall survival between the study groups when adjusting for stage and age (HR 1.08, p = 0.84).
- Superficial inguinal LND had no significant difference in rate of recurrence or overall survival when compared to deep inguinal LND in patients with vulvar SCC. Those who received a deep LND had a significant increase in overall morbidity, including lymphedema, readmission, and infection. For patients who cannot undergo or fail sentinel lymph node mapping, a superficial inguinal lymph node dissection may have similar outcomes in recurrence and overall survival with a reduction in overall morbidity as compared to a complete, or deep, lymph node dissection.
Kokila Thenuwara, Franklin Dexter, Richard H. Epstein
Perioperative Care and Operating Room Management, Volume 28, September 2022, 100277, epub ahead of print.
Background: Our goal was to assess whether anesthesia workforce limited surgical obstetrical care in the rural US state of Iowa. All Iowa hospitals with obstetrics have anesthesia practitioners (i.e., constraints would be functional, not related to having no anesthesia coverage). Our hypothesis #1 was that scheduling for cesarean delivery would functionally be separate from other inpatient operating room scheduling. Our hypothesis #2 was absence of systematic differences among hospitals in their distributions of cesarean deliveries between weekends and regular workdays.
- The retrospective cohort study included all inpatient surgical cases at hospitals with cesarean births in the state of Iowa October 2015 through June 2021. There were analyzed 112 hospitals × 2100 days × 2 numbers, counts of cesarean deliveries and counts of all other surgical cases.
Results: The incremental risk ratio between daily cesarean deliveries and other inpatient surgical cases was 1.00 per cesarean delivery (99% confidence interval 0.99 to 1.01). Thus, doing another cesarean delivery was not associated with either a proportional reduction (ratio <1) or increase (ratio >1) in other cases performed on the same day. Multiple sensitivity analyses showed the same results. In addition, there was no association in cesarean deliveries between hospitals’ percentages on weekends and overall weekly numbers (P = 0.08). Multiple sensitivity analyses showed the same results, no systematic differences between large versus small obstetrical programs in the distributions of cesareans between weekends versus workdays. Finally, among the 19/73 hospitals ending obstetrics during the study period, all continued to perform surgery.
Conclusions: Limitations in the anesthesia workforce did not constrain surgical obstetrical care statewide. Similarly, cesarean births were at most negligibly causing other inpatient surgical cases to be postponed to later days.
Cardillo N, Devor EJ, Pedra Nobre S, Newtson A, Leslie K, Bender DP, Smith BJ, Goodheart MJ, Gonzalez-Bosquet J.
Cancers (Basel). 2022 Jul 21;14(14):3554.
Advanced high-grade serous (HGSC) ovarian cancer is treated with either primary surgery followed by chemotherapy or neoadjuvant chemotherapy followed by interval surgery. The decision to proceed with surgery primarily or after chemotherapy is based on a surgeon's clinical assessment and prediction of an optimal outcome. Optimal and complete cytoreductive surgery are correlated with improved overall survival. This clinical assessment results in an optimal surgery approximately 70% of the time. We hypothesize that this prediction can be improved by using biological tumor data to predict optimal cytoreduction. With access to a large biobank of ovarian cancer tumors, we obtained genomic data on 83 patients encompassing gene expression, exon expression, long non-coding RNA, micro RNA, single nucleotide variants, copy number variation, DNA methylation, and fusion transcripts. We then used statistical learning methods (lasso regression) to integrate these data with pre-operative clinical information to create predictive models to discriminate which patient would have an optimal or complete cytoreductive outcome. These models were then validated within The Cancer Genome Atlas (TCGA) HGSC database and using machine learning methods (TensorFlow). Of the 124 models created and validated for optimal cytoreduction, 21 performed at least equal to, if not better than, our historical clinical rate of optimal debulking in advanced-stage HGSC as a control. Of the 89 models created to predict complete cytoreduction, 37 have the potential to outperform clinical decision-making. Prospective validation of these models could result in improving our ability to objectively predict which patients will undergo optimal cytoreduction and, therefore, improve our ovarian cancer outcomes.
Copeland LJ, Brady MF, Burger RA, Rodgers WH, Huang HQ, Cella D, O'Malley DM, Street DG, Tewari KS, Morris RT, Lowery WJ, Miller DS, Dewdney SB, Spirtos NM, Lele SB, Guntupalli S, Ueland FR, Glaser GE, Mannel RS, DiSaia PJ.
J Clin Oncol. 2022 Jun 27:JCO2200146. doi: 10.1200/JCO.22.00146. Epub ahead of print.
Purpose: To compare taxane maintenance chemotherapy, paclitaxel (P) and paclitaxel poliglumex (PP), with surveillance (S) in women with ovarian, peritoneal, or fallopian tube (O/PC/FT) cancer who attained clinical complete response after first-line platinum-taxane therapy.
- Women diagnosed with O/PC/FT cancer who attained clinical complete response after first-line platinum-taxane-based chemotherapy were randomly allocated 1:1:1 to S or maintenance, P 135 mg/m2 once every 28 days for 12 cycles, or PP at the same dose and schedule. Overall survival (OS) was the primary efficacy end point.
- Between March 2005 and January 2014, 1,157 individuals were enrolled. Grade 2 or worse GI adverse events were more frequent among those treated with taxane (PP: 20%, P: 27% v S: 11%). Grade 2 or worse neurologic adverse events occurred more often with taxane treatment (PP: 46%, P: 36% v S: 14%). At the fourth scheduled interim analysis, both taxane regimens passed the OS futility boundary and the Data Monitoring Committee approved an early release of results. With a median follow-up of 8.1 years, 653 deaths were reported; none were attributed to the study treatment. Median survival durations were 58.3, 56.8, and 60.0 months for S, P, and PP, respectively. Relative to S, the hazard of death for P was 1.091 (95% CI, 0.911 to 1.31; P = .343) and for PP, it was 1.033 (95% CI, 0.862 to 1.24; P = .725). The median times to first progression or death (PFS) were 13.4, 18.9, and 16.3 months for S, P, and PP, respectively. Hazard ratio = 0.801; 95% CI, 0.684 to 0.938; P = .006 for P and hazard ratio = 0.854; 95% CI, 0.729 to 1.00; P = .055 for PP.
- Maintenance therapy with P and PP did not improve OS among patients with newly diagnosed O/tubal/peritoneal cancer, but may modestly increase PFS. GI and neurologic toxicities were more frequent in the taxane treatment arms.
Mancuso AC, Mengeling MA, Holcomb A, Ryan GL.
Am J Obstet Gynecol. 2022 Jul 13:S0002-9378(22)00538-5. doi: 10.1016/j.ajog.2022.07.002. Epub ahead of print.
Background: Veterans experience many potentially hazardous exposures during their service, but little is known about the possible impact of these exposures on reproductive health.
- To assess the association between infertility and environmental, chemical, or hazardous material exposures among United States Veterans
STUDY DESIGN: We examined self-reported cross-sectional data from a national sample of female and male United States Veterans aged 20-45 separated from service for ≤10 years. Data were obtained via a computer-assisted telephone interview lasting an average of 1 hour 27 minutes that assessed demographics, general and reproductive health, and lifetime and military exposures. Logistic regression models were used to evaluate associations between exposures to environmental, chemical, and hazardous materials and infertility as defined by two different definitions: unprotected intercourse for 12 or more months without conception and trying to conceive for 12 or more months without conception.
- Of the Veterans included in this study, 592/1194 (49.6%) women and 727/1,407 (51.7%) men met the unprotected intercourse definition for infertility and 314/781 (40.2%) women and 270/775 (34.8%) men met the trying to conceive definition for infertility. Multiple individual exposure rates were found to be higher in women and men Veterans with self-reported infertility, including petrochemicals and polychlorinated biphenyls, which were higher in both the men and women groups reporting infertility by either definition. Importantly, there were no queried exposures self-reported at higher rates in the non-infertile groups. Veterans reporting infertility also reported a higher number of total exposures with a mean ± standard deviation of 7.61 ± 3.87 exposures for the women with infertility compared to 7.13 ± 3.67 for the non-infertile group (p=.030) and 13.17 ± 4.19 for Veteran men with infertility compared to 12.54 ± 4.10 for the non-infertile group (p=.005) using the unprotected intercourse definition, and 7.69 ± 3.79 for the women with infertility compared to 7.02 ± 3.57 for the non-infertile group (p=.013) and 13.77 ± 4.17 for the Veteran men with infertility compared to 12.89 ± 4.08 for the non-infertile group (p=.005) using the trying to conceive definition.
- These data identified an association between infertility and environmental, chemical, and hazardous materials Veterans were exposed to during military service. Although this study is limited by the self-reported and unblinded data collection from a survey, and causation between exposures and infertility cannot be proven, it does show that Veterans encounter many exposures during their service and calls for further research into the possible link between Veteran exposures and reproductive health.
Iwamoto A, Van Voorhis BJ, Summers KM, Sparks A, Mancuso AC.
Fertil Steril. 2022 Jul 11:S0015-0282(22)00387-9. doi: 10.1016/j.fertnstert.2022.06.009. Epub ahead of print.
Objective: To compare the cumulative live birth rates (CLBRs) and cost effectiveness of intracytoplasmic sperm injection (ICSI) and conventional in vitro fertilization (cIVF) for non-male factor infertility.
- A retrospective cohort study.
- Society for Assisted Reproductive Technology clinics.
- A total of 46,967 patients with non-male factor infertility with the first autologous oocyte retrieval cycle between January 2014 and December 2015.
- None.
Main outcome measure(s): The primary outcomes were CLBR, defined as up to 1 live birth from an autologous retrieval cycle between 2014 and 2015, and linked fresh and frozen embryo transfers through 2016. The secondary outcomes included miscarriage rate, 2 pronuclei per oocyte retrieved, and the total number of transferred and frozen embryos. Analyses were performed on subsamples with and without preimplantation genetic testing for aneuploidy (PGT-A). A cost analysis was performed to determine the costs accrued by ICSI.
- Among cycles without PGT-A in patients with non-male factor infertility, the CLBR was 60.9% for ICSI cycles vs. 64.3% for cIVF cycles, a difference that was not significantly different after adjustment for covariates (adjusted risk ratio, 0.99; 95% confidence interval, 0.99-1.00). With PGT-A, no difference in CLBR was found between ICSI and cIVF cases after adjustment (64.7% vs. 69.0%, respectively; adjusted risk ratio, 0.97; 95% confidence interval, 0.93-1.01). The patients were charged an estimated additional amount of $37,476,000 for ICSI without genetic testing and an additional amount of $7,213,500 for ICSI with PGT-A over 2 years by Society for Assisted Reproductive Technology clinics.
- In patients with non-male factor infertility, ICSI did not improve CLBR. Given the additional cost and the lack of CLBR benefit, our data show that the routine use of ICSI in patients with non-male factor infertility is not warranted.
Masse N, Dexter F, Wong CA.
Obstet Gynecol. 2022 Aug 1;140(2):181-186. doi: 10.1097/AOG.0000000000004857. Epub 2022 Jul 6.
Objective: To evaluate whether the administration of prophylactic methylergonovine in addition to oxytocin in patients undergoing intrapartum cesarean birth reduces the need for additional uterotonic agents.
- This was a single-center, placebo-controlled, randomized trial of patients undergoing intrapartum cesarean birth. Patients were randomly allocated to receive intravenous oxytocin 300 mL/minute plus intramuscular methylergonovine 0.2 mg (1 mL) or intravenous oxytocin 300 mL/minute plus intramuscular normal saline (1 mL). The primary outcome was the receipt of additional uterotonic agents. Secondary outcomes included surgeon assessment of uterine tone, incidence of postpartum hemorrhage, quantitative blood loss, and blood transfusion. To detect a twofold decrease in the need for additional uterotonic agents (assuming a 42% baseline) with a two-sided type 1 error of 5% and power of 80%, a sample size of 76 patients per group was required.
- From June 2019 through February 2021, 80 patients were randomized to receive methylergonovine plus oxytocin and 80 were randomized to receive to oxytocin alone. Significantly fewer patients who were allocated to the methylergonovine group received additional uterotonic agents (20% vs 55%, relative risk [RR] 0.4, 95% CI 0.2-0.6). Participants receiving methylergonovine were more likely to have satisfactory uterine tone (80% vs 41%, RR 1.9, 95% CI 1.5-2.6), lower incidence of postpartum hemorrhage (35% vs 59%, RR 0.6, 95% CI 0.4-0.9), lower mean quantitative blood loss (967 mL vs 1,315 mL; mean difference 348, 95% CI 124-572), and a lower frequency of blood transfusion (5% vs 23%, RR 0.2, 95% CI 0.1-0.6).
- The administration of prophylactic methylergonovine in addition to oxytocin in patients undergoing intrapartum cesarean birth reduces the need for additional uterotonic agents.
Occupation and Semen Parameters in a Cohort of Fertile Men.
Meyer JD, Brazil C, Redmon JB, Wang C, Swan SH.
J Occup Environ Med. 2022 Jul 19. doi: 10.1097/JOM.0000000000002607. Epub ahead of print.
Objective: We examined associations between occupation and semen parameters in demonstrably fertile men in the Study for Future Families.
- Associations of occupation and workplace exposures with semen volume, sperm concentration, motility, and morphology were assessed using generalized linear modeling.
- Lower sperm concentration and motility were seen in installation, maintenance, and repair occupations. Higher exposure to lead, and to other toxicants, was seen in occupations with lower mean sperm concentrations (prevalence ratio for lead: 4.1; pesticides/insecticides: 1.6; solvents: 1.4). Working with lead for more than 3 months was associated with lower sperm concentration, as was lead exposure outside of work.
- We found evidence in demonstrably fertile men for reduced sperm quality with lead, pesticide/herbicide, and solvent exposure. These results may identify occupations where protective measures against male reproductive toxicity might be warranted.
Welch BM, Keil AP, Buckley JP, Calafat AM, Christenbury KE, Engel SM, O'Brien KM, Rosen EM, James-Todd T, Zota AR, Ferguson KK; Pooled Phthalate Exposure and Preterm Birth Study Group, Alshawabkeh AN, Cordero JF, Meeker JD, Barrett ES, Bush NR, Nguyen RHN, Sathyanarayana S, Swan SH, Cantonwine DE, McElrath TF, Aalborg J, Dabelea D, Starling AP, Hauser R, Messerlian C, Zhang Y, Bradman A, Eskenazi B, Harley KG, Holland N, Bloom MS, Newman RB, Wenzel AG, Braun JM, Lanphear BP, Yolton K, Factor-Litvak P, Herbstman JB, Rauh VA, Drobnis EZ, Redmon JB, Wang C, Binder AM, Michels KB, Baird DD, Jukic AMZ, Weinberg CR, Wilcox AJ, Rich DQ, Weinberger B, Padmanabhan V, Watkins DJ, Hertz-Picciotto I, Schmidt RJ.
JAMA Pediatr. 2022 Jul 11:e222252. doi: 10.1001/jamapediatrics.2022.2252. Epub ahead of print.
Importance: Phthalate exposure is widespread among pregnant women and may be a risk factor for preterm birth.
- To investigate the prospective association between urinary biomarkers of phthalates in pregnancy and preterm birth among individuals living in the US.
Design, setting, and participants: Individual-level data were pooled from 16 preconception and pregnancy studies conducted in the US. Pregnant individuals who delivered between 1983 and 2018 and provided 1 or more urine samples during pregnancy were included.
- Urinary phthalate metabolites were quantified as biomarkers of phthalate exposure. Concentrations of 11 phthalate metabolites were standardized for urine dilution and mean repeated measurements across pregnancy were calculated.
Main outcomes and measures: Logistic regression models were used to examine the association between each phthalate metabolite with the odds of preterm birth, defined as less than 37 weeks of gestation at delivery (n = 539). Models pooled data using fixed effects and adjusted for maternal age, race and ethnicity, education, and prepregnancy body mass index. The association between the overall mixture of phthalate metabolites and preterm birth was also examined with logistic regression. G-computation, which requires certain assumptions to be considered causal, was used to estimate the association with hypothetical interventions to reduce the mixture concentrations on preterm birth.
- The final analytic sample included 6045 participants (mean [SD] age, 29.1 [6.1] years). Overall, 802 individuals (13.3%) were Black, 2323 (38.4%) were Hispanic/Latina, 2576 (42.6%) were White, and 328 (5.4%) had other race and ethnicity (including American Indian/Alaskan Native, Native Hawaiian, >1 racial identity, or reported as other). Most phthalate metabolites were detected in more than 96% of participants. Higher odds of preterm birth, ranging from 12% to 16%, were observed in association with an interquartile range increase in urinary concentrations of mono-n-butyl phthalate (odds ratio [OR], 1.12 [95% CI, 0.98-1.27]), mono-isobutyl phthalate (OR, 1.16 [95% CI, 1.00-1.34]), mono(2-ethyl-5-carboxypentyl) phthalate (OR, 1.16 [95% CI, 1.00-1.34]), and mono(3-carboxypropyl) phthalate (OR, 1.14 [95% CI, 1.01-1.29]). Among approximately 90 preterm births per 1000 live births in this study population, hypothetical interventions to reduce the mixture of phthalate metabolite levels by 10%, 30%, and 50% were estimated to prevent 1.8 (95% CI, 0.5-3.1), 5.9 (95% CI, 1.7-9.9), and 11.1 (95% CI, 3.6-18.3) preterm births, respectively.
Conclusions and relevance: Results from this large US study population suggest that phthalate exposure during pregnancy may be a preventable risk factor for preterm delivery.
Preti M, Joura E, Vieira-Baptista P, Van Beurden M, Bevilacqua F, Bleeker MCG, Bornstein J, Carcopino X, Chargari C, Cruickshank ME, Erzeneoglu BE, Gallio N, Heller D, Kesic V, Reich O, Temiz BE, Woelber L, Planchamp F, Zodzika J, Querleu D, Gultekin M.
J Low Genit Tract Dis. 2022 Jul 1;26(3):229-244. doi: 10.1097/LGT.0000000000000683. Epub 2022 Jun 21.
The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) developed consensus statements on pre-invasive vulvar lesions in order to improve the quality of care for patients with vulvar squamous intraepithelial neoplasia, vulvar Paget disease in situ, and melanoma in situ. For differentiated vulvar intraepithelial neoplasia (dVIN), an excisional procedure must always be adopted. For vulvar high-grade squamous intraepithelial lesion (VHSIL), both excisional procedures and ablative ones can be used. The latter can be considered for anatomy and function preservation and must be preceded by several representative biopsies to exclude malignancy. Medical treatment (imiquimod or cidofovir) can be considered for VHSIL. Recent studies favor an approach of using imiquimod in vulvar Paget's disease. Surgery must take into consideration that the extension of the disease is usually wider than what is evident in the skin. A 2 cm margin is usually considered necessary. A wide local excision with 1 cm free surgical margins is recommended for melanoma in situ. Following treatment of pre-invasive vulvar lesions, women should be seen on a regular basis for careful clinical assessment, including biopsy of any suspicious area. Follow-up should be modulated according to the risk of recurrence (type of lesion, patient age and immunological conditions, other associated lower genital tract lesions).
Endometrial thickness: How thin is too thin?
Jacobs EA, Van Voorhis B, Kawwass JF, Kondapalli LA, Liu K, Dokras A.
Fertil Steril. 2022 Aug;118(2):249-259. doi: 10.1016/j.fertnstert.2022.05.033.
Weldon CB, Trosman JR, Liang SY, Douglas MP, Scheuner MT, Kurian A, Roscow B, Erwin D, Phillips KA.
J Genet Couns. 2022 Jul 28. doi: 10.1002/jgc4.1614. Epub ahead of print.
Multi-cancer gene panels for hereditary cancer syndromes (hereditary cancer panels, HCPs) are widely available, and some laboratories have programs that limit patients' out-of-pocket (OOP) cost share. However, little is known about practices by cancer genetic counselors for discussing and ordering an HCP and how insurance reimbursement and patient out-of-pocket share impact these practices. We conducted a survey of cancer genetic counselors based in the United States through the National Society of Genetic Counselors to assess the impact of reimbursement and patient OOP share on ordering of an HCP and hereditary cancer genetic counseling. Data analyses were conducted using chi-square and t tests. We received 135 responses (16% response rate). We found that the vast majority of respondents (94%, 127/135) ordered an HCP for patients rather than single-gene tests to assess hereditary cancer predisposition. Two-thirds of respondents reported that their institution had no protocol related to discussing HCPs with patients. Most respondents (84%, 114/135) indicated clinical indications and patients' requests as important in selecting and ordering HCPs, while 42%, 57/135, considered reimbursement and patient OOP share factors important. We found statistically significant differences in reporting of insurance as a frequently used payment method for HCPs and in-person genetic counseling (84% versus 59%, respectively, p < 0.0001). Perceived patient willingness to pay more than $100 was significantly higher for HCPs than for genetic counseling(41% versus 22%, respectively, p < 0.01). In sum, genetic counselors' widespread selection and ordering of HCPs is driven more by clinical indications and patient preferences than payment considerations. Respondents perceived that testing is more often reimbursed by insurance than genetic counseling, and patients are more willing to pay for an HCP than for genetic counseling. Policy efforts should address this incongruence in reimbursement and patient OOP share. Patient-centered communication should educate patients on the benefit of genetic counseling.