Bilateral Singapore fasciocutaneous flap after anterior vulvectomy and distal urethrectomy for localized recurrent vulvar carcinoma.

Introduction: Vulvar cancer has an overall low incidence, accounting for approximately 3-5% of all gynecological malignancies.Case: We present a case of locally recurrent Stage IIIA squamous cell carcinoma of the vulva in a 51-year-old healthy African American female. She was initially treated with primary chemoradiation with cisplatin sensitization and boost to primary tumor up to 70 Gray. Post-treatment biopsies revealed complete pathologic response. She later presented with local recurrence to the primary site of the clitoris and vulva, with no evidence of metastasis on imaging, with progressive disease despite treatment with immunotherapy. Methods: Biopsy-proven disease progression was present on the clitoris, entire left labia minora, and a portion of the right labia minora with no evidence of metastasis on imaging. Surgical resection for localized recurrence was recommended, and she underwent radical anterior vulvectomy, distal urethrectomy, and vulvar reconstruction with bilateral Singapore fasciocutaneous flap as part of a multidisciplinary team. Patient underwent several prophylactic hyperbaric oxygen treatments. There were no issues with postoperative wound healing. Conclusion: Treatment with radical excision often requires multidisciplinary teams for complex reconstructions to restore vulvar anatomy in the setting of prior radiation, especially for those patients desiring the ability to have penetrative intercourse in the future. There are few surgical videos that describe these types of vulvar excisions and subsequent reconstructions. This video provides a unique approach to vulvar reconstruction in a previously irradiated field.

Disease progression, survival, and molecular disparities in Black and White patients with endometrioid endometrial carcinoma in real-world registries and GOG/NRG oncology randomized phase III clinical trials.

OBJECTIVE: Investigate racial disparities in outcomes and molecular features in Black and White patients with endometrioid endometrial carcinoma (EEC). METHODS: Black and White patients diagnosed with EEC who underwent hysterectomy ± adjuvant treatment in SEER, National Cancer Database (NCDB), the Genomics Evidence Neoplasia Information Exchange (GENIE) project (v.13.0), and eight NCI-sponsored randomized phase III clinical trials (RCTs) were studied. Hazard ratio (HR) and 95% confidence interval (CI) were estimated for cancer-related death (CRD), non-cancer death (NCD), and all-cause death. RESULTS: Black (n = 4397) vs. White (n = 47,959) patients in SEER had a HR (95% CI) of 2.04 (1.87-2.23) for CRD and 1.22 (1.09-1.36) for NCD. In NCDB, the HR (95% CI) for death in Black (n = 13,468) vs. White (n = 155,706) patients was 1.52 (1.46-1.58) dropping to 1.29 (1.23-1.36) after propensity-score matching for age, comorbidity, income, insurance, grade, stage, LVSI, and treatment. In GENIE, Black (n = 109) vs. White (n = 1780) patients had fewer PTEN, PIK3R1, FBXW7, NF1, mTOR, CCND1, and PI3K-pathway-related gene mutations. In contrast, TP53 and DNA-repair-related gene mutation frequency as well as tumor mutational burden-high status were similar in Black and White patients. In RCTs, Black (n = 187) vs. White (n = 2877) patients were more likely to have advanced or recurrent disease, higher grade, worse performance status and progressive disease. Risk of death in Black vs. White patients in RCTs was 2.19 (1.77-2.71) persisting to 1.32 (1.09-1.61) after matching for grade, stage, and treatment arm while balancing age and performance status. CONCLUSIONS: Differences exist in clinical presentation, outcomes, and molecular features in Black vs. White patients with EEC in real-world registries and RCTs. Targeted-drug development, strategies to modify social determinants, and diverse inclusion in RCTs are approaches to reduce disparities.

Rapid Root Cause Analysis: Improving OBGYN Resident Exposure to Quality Improvement and Patient Safety Curricula.

Introduction Each year, millions of patients in the United States experience harm as a result of the healthcare they receive. One mechanism used by health systems to learn how and why errors occur is root cause analysis (RCA). RCA teams develop action plans to create and implement systemic changes in healthcare delivery in order to prevent future harm. The American Council on Graduate Medical Education (ACGME) recognizes the importance of analyzing adverse events, and it requires that all residents participate in real or simulated patient safety activities, such as RCAs. Often, institutional RCAs necessitate the assimilation of participants on short notice and demand considerable time investment, limiting the feasible participation of graduate medical education (GME) trainees. This presents a gap between ACGME expectations and the reality of resident involvement in patient safety activities. We present the first iteration of a quality improvement project encompassing a three-hour resident physician training course with simulated RCA-experiential learning. The purpose of this project was to produce a condensed, educational RCA experience that adequately trains all GME learners to serve as informed healthcare safety advocates while also satisfying ACGME requirements. Methods The course ("rapid RCA") was conducted during protected weekly academic training. All residents of the San Antonio Uniformed Services Health Education Consortium (SAUSHEC) Obstetrics and Gynecology (OBGYN) residency program who had not previously participated in a real or simulated RCA were required to take the "rapid RCA." Pre- and post-course surveys were completed anonymously to assess baseline knowledge, new knowledge gained from the course, and attitudes toward the course and its importance to resident training. Results Fourteen OBGYN residents attended the "rapid RCA," indicating that 64% (14 out of 22) of the program had no previous experience or opportunity to participate in a real or simulated RCA. Participation in the course demonstrated a significant gain of new knowledge with an increase from 0/14 to 10/14 (71%) residents correctly answering all pre- and post-course questions, respectively (p < 0.001). Additionally, on a Likert scale from 1 to 5, with 5 indicating "expert level," residents indicated they felt more comfortable on patient safety topics after taking the course (mean pre-course score 1.85 to post-course score 3.64, p < 0.001). All participants indicated they would prefer to take the "rapid RCA" as opposed to the only available local alternative option for a simulated RCA, currently offered as a full-day intensive course. Conclusion A meaningful increase in patient safety knowledge and attitudes toward topics covered in an RCA was demonstrated through the implementation of a "rapid RCA" in OBGYN residents. We plan to incorporate this into our annual curriculum to satisfy ACMGE requirements. This format could be adapted for other specialties as applicable.

High-Risk Gestational Trophoblastic Neoplasia from a Homozygous NLRP7 Mutation.

•NLRP7 germline mutation can result in high risk gestational trophoblastic neoplasia.•No successful reproductive outcomes have been reported with homozygous NLRP7 mutation.•Germline testing should be considered for patients presenting with recurrent gestational trophoblastic disease.•Once an NLRP7 mutation is diagnosed, consultation with reproductive endocrinology is necessary to discuss future fertility.•Further research is needed in rare cases regarding gestational trophoblastic neoplasia recurrence and reproductive outcomes.

Mandatory HPV Vaccination; Opportunity to Save Lives, Improve Readiness and Cut Costs.

Human papillomavirus (HPV) is the most common sexually transmitted infection (STI) in the U.S. military and accounts for more healthcare visits than the next two most common STIs combined. Human papillomavirus is preventable with a safe, effective, prophylactic vaccine that has been available since 2006, yet vaccination rates remain low. The vaccine is approved for females and males aged 9-45 years for prevention of HPV-related dysplasia and cancers. Although it is recommended by the Centers for Disease Control and Prevention (CDC)'s Advisory Committee on Immunization Practices (ACIP), it is not part of the U.S. military's mandatory vaccine list. Human papillomavirus does not just affect female service members-male service members have a higher reported seropositive rate than their civilian counterparts and can develop oropharyngeal, anal, or penile cancers as sequelae of HPV. Oropharyngeal cancer, more common in males, is the fastest growing and most prevalent HPV-related cancer in the USA. Several countries, such as Australia and Sweden, have successfully implemented mandatory vaccine programs and have seen rates of HPV-related diseases, including cancer, decline significantly. Some models project that cervical cancer, which is the fifth-most common cancer in active duty women, will be eliminated in the next 20 years as a result of mandatory vaccination programs. Between higher seropositive rates and lack of widespread vaccination, HPV dysplasia and cancer result in lost work time, decreased force readiness, negative monetary implications, and even separation from service. With more than half of the 1.3 million service members in the catch-up vaccination age range of less than 26 years of age, we are poised to have a profound impact through mandatory active duty service member vaccination. Although multiple strategies for improving vaccination rates have been proposed, mandatory vaccination would be in line with current joint service policy that requires all ACIP-recommended vaccines. It is time to update the joint service guidelines and add HPV vaccine to the list of mandatory vaccines.

Jupiter microtubule-associated homolog 1 (JPT1): A predictive and pharmacodynamic biomarker of metformin response in endometrial cancers.

Preoperative use of metformin in obese women with endometrioid endometrial cancer (EEC) reduces tumor proliferation and inhibits the mammalian target of rapamycin pathway, though is only effective in select cases. This study sought to identify a predictive and/or pharmacodynamic proteomic signature of metformin response to tailor its pharmacologic use. Matched pre- and post-metformin-treated tumor tissues from a recently completed preoperative window trial of metformin in EEC patients (ClinicalTrials.gov: NCT01911247) were analyzed by mass spectrometry (MS)-based proteomic and immunohistochemical analyses. Jupiter microtubule-associated homolog 1 (JPT1) was significantly elevated in metformin responders (n = 13) vs nonresponders (n = 7), and found to decrease in abundance in metformin responders following treatment; observations that were verified by immunohistochemical staining for JPT1. Metformin response and loss of JPT1 were assessed in RL95-2 and ACI-181 endometrial cancer (EC) cell lines. We further identified that silencing of JPT1 abundance does not alter cellular response to metformin or basal cell proliferation, but that JPT1 abundance does decrease in response to metformin treatment in RL95-2 and ACI-181 EC cell lines. These data suggest that JPT1 represents a predictive and pharmacodynamic biomarker of metformin response that, if validated in larger patient populations, may enable preoperative EEC patient stratification to metformin treatment and the ability to monitor patient response.

Nestin: A biomarker of aggressive uterine cancers.

OBJECTIVE: Evidence of potential prognostic and predictive value for nestin was investigated in well-annotated uterine cancers (UCs). METHODS: Nestin expression and previously-published biomarkers were evaluated by immunohistochemistry (IHC) in UC tissue microarrays. Biomarkers were categorized as low vs. high, and nestin was cut at 10% positive staining. Relationship between nestin and clinicopathologic factors, biomarkers and outcome were evaluated using exact/log-rank testing or logistic/Cox modeling. RESULTS: There were 323 eligible cases, 34% had advanced stage disease, 37% had type II disease, and 5% were carcinosarcomas. High nestin, observed in 19% of cases, was more common in advanced vs. early stage disease, type II cancers or uterine carcinosarcoma vs. type I cancers, grade 3 disease, positive lymphovascular space invasion (LVSI) and tumors >6cm (p<0.05). Nestin was inversely correlated with ER, PR and TFF3, and correlated with p53 and IMP3. Women with high vs. low nestin had worse progression-free survival (PFS) and cancer-specific survival overall, and worse PFS in the subset who received no adjuvant therapy or radiation, or had early stage, type I disease or tumors with both low and high ER, PR, TFF3, PTEN, p53 or IMP3. The relationship between nestin and PFS was independent of stage, LVSI and risk categorization but not type of UC. CONCLUSIONS: High nestin was more common in UCs with aggressive features and poor outcome. Nestin may represent a predictive biomarker for treatment selection for patients previously considered to be lower risk and a candidate for no or radiation-based adjuvant therapy, and compliment ER/PR testing.

Adnexal Incarceration in a Posterior Pelvic Peritoneal Defect Mimics Ovarian Torsion.

Surgery for suspected ovarian torsion sometimes reveals unexpected sources of pelvic pain, such as internal hernias, adhesions, or anatomic defects. A 23-year-old nulligravida with Alagille syndrome was taken to the operating room with suspected ovarian torsion. Intraoperatively, the right adnexa bulged out of a right-sided, posterior peritoneal cleft that incarcerated most of the enlarged ovary. No ovarian torsion was identified. The left adnexa appeared to be normal; however, it dwelled within a left-sided posterior peritoneal cleft. The bilateral posterior peritoneal defects that housed the adnexa were likely of congenital etiology. Although adnexal incarceration is a rare finding at surgery for suspected ovarian torsion, it should be part of the differential diagnosis when evaluating acute pelvic pain.

An Uncommon Case of Bilateral Peroneal Nerve Palsy following Delivery: A Case Report and Review of the Literature.

Peroneal nerve palsy is an infrequent but potential complication of childbirth. Bilateral peroneal palsy is particularly rare following delivery with few reported cases. A 38-year-old gravida 1, para 0 underwent a prolonged second stage of labor, was diagnosed with an arrest of descent, and subsequently underwent an uncomplicated primary cesarean section. The patient was diagnosed with bilateral peroneal neuropathy four days after delivery. By two months postpartum, her foot drop had improved by 85% and the remainder of her symptoms resolved. Awareness of the risks of a peroneal neuropathy as well as implementation of preventive measures is important for members of the delivery team. Regional anesthesia during labor is a risk factor for the development of a peroneal neuropathy.

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.

Takotsubo cardiomyopathy following laparoscopic port placement in a patient with ovarian cancer.

► Gynecologic oncology patients can be exposed to both chronic and acute physical and emotional stress. ► Gynecologic oncology patients appear to represent an at-risk population for the development of Takotsubo's cardiomyopathy.