Vaginal Cuff Dehiscence in Transgender Patients After Minimally Invasive Hysterectomy.

STUDY OBJECTIVE: To compare rates of vaginal cuff dehiscence (VCD) in transgender patients with cisgender patients after minimally invasive hysterectomy (MIH). DESIGN: We performed a single-surgeon, retrospective cohort analysis comparing the rates of VCD in patients undergoing MIH for gender affirmation with other indications (benign, malignant, prophylactic) with our study surgeon between January, 2015, and December, 2021. SETTING: Major, urban, academic tertiary care hospital in the United States. PATIENTS: 166 patients met inclusion criteria with 49 of those patients undergoing MIH (29.5%) for gender affirmation. Of the remaining 117 patients, 92 (78.6%) underwent MIH for cancer, 15 (12.8%) for prophylaxis, and 10 (8.5%) for benign indications. INTERVENTIONS: Not applicable. MEASUREMENTS: We assessed included patients for baseline demographics, presence of risk factors for VCD, details of index hysterectomy, and details of cuff dehiscence events. MAIN RESULTS: Transgender patients tended to be younger at the time of surgery, but demographics were otherwise similar between both groups. Most transgender patients (n = 36, 73.5%) had both ovaries removed at the time of hysterectomy, 100% were on testosterone therapy pre- and postoperatively, and none used supplementary estrogen. Three of the 49 transgender patients (6.1%) experienced postoperative dehiscence of the vaginal cuff compared with 2 of the 117 cisgender patients (1.7%). This failed to reach statistical significance; however, our descriptive analysis showed that all cases of dehiscence in the cisgender group had identifiable precipitating factors (i.e., trauma). By comparison, all cases of dehiscence in the transgender group were spontaneous with few identifiable risk factors. CONCLUSION: Transgender patients undergoing MIH may be at increased risk of VCD, although the rarity of this surgical complication precluded determination of statistical significance in our data set. We propose testosterone exposure as a possible risk factor for VCD, although we cannot exclude other factors, such as young age, as drivers of VCD in this population. Future studies of biospecimens are needed to evaluate for cellular differences in these patients.

Association between adherence to posttreatment National Comprehensive Cancer Network (NCCN) surveillance guidelines and detection of recurrent uterine cancer.

OBJECTIVE: To identify correlations between disease recurrence and adherence to NCCN posttreatment surveillance guidelines in patients who develop recurrent uterine cancer. METHODS: Retrospective analysis identified patients (n = 60) with recurrent uterine cancer and at least one surveillance visit with a gynecologic oncologist between 2011 and 2020. Adherence to NCCN guidelines and details of recurrence were recorded. RESULTS: Recurrent uterine cancer was identified in 60 patients with an average time to recurrence (TTR) of 25 months. Of those, 39 (65%) were adherent to NCCN surveillance guidelines and 36 (60%) were symptomatic at the time of recurrence diagnosis. Asymptomatic recurrence was diagnosed by imaging in 11 (46%), physical exam in 7 (29%), and blood work in 6 (25%) patients. Patients who were adherent to NCCN guidelines were diagnosed with recurrence on average 11 months earlier (p = 0.0336). Adherence was an independent predictor of TTR for all patients regardless of symptoms. There was no significant effect of age, race, primary language, or stage of disease on adherence. CONCLUSION: Adherence to NCCN posttreatment surveillance guidelines for uterine cancer is independently associated with an earlier diagnosis of recurrence.

Opportunities Missed: Cervix Cancer Screening Failures in Women Aged 65 and Older.

OBJECTIVES: This study aimed to determine the screening history and associated outcomes of women diagnosed with cervical cancer after age 65. METHODS: All patients from 2012 to 2021 diagnosed with squamous, adenocarcinoma, neuroendocrine, or adenosquamous cervical cancer after age 65 in a single managed care organization (MCO) were included in this retrospective cohort study. Demographic, medical, screening, pathologic, follow-up, and treatment data were extracted. Statistical analysis was done using chi-square test and logistic regression. Cancer-specific survival was estimated using the Kaplan-Meier method. RESULTS: Of 2,175 patients screened, 209 met inclusion criteria. Only 26.3% of patients had appropriate cervical cancer screening and 41% of patients died of their disease. Managed care organization membership duration of more than 5 years positively correlated with proper cervical cancer screening ( p < .001); however, 64% of the long-term members still did not meet criteria to end screening at age 65, with 42.6% of these patients having more than 25 physician visit opportunities to address screening. Increased physician visits correlated with earlier stage at diagnosis of cervical cancer ( p = .012). Median cancer-specific survival was significantly better in properly screened patients at 68 vs 30 months, respectively ( p = .03). CONCLUSIONS: Most patients diagnosed with cervical cancer after age 65 did not have adequate previous screening, including those who were MCO members for more than 5 years. There were many missed opportunities for screening, despite multiple provider touchpoints. The authors' data suggest that adequate screening confers a survival benefit secondary to earlier stage at diagnosis. Further study in this age group is needed to redefine the criteria to end cervix cancer screening.

A case of endometrial intraepithelial neoplasia in a transgender man on testosterone therapy.

Testosterone is commonly used as gender-affirming therapy to induce masculinization in transmasculine individuals. The effects of testosterone therapy on endometrial tissue are complex, and while some patients experience endometrial atrophy while taking testosterone, others do not. Reports of gynecologic malignancies, and endometrial cancer in particular, in transmasculine patients taking testosterone are extremely rare (Urban et al., May 2011, Jeevananthan and Iyengar, 2021, Agnieszka Bobola, 2021). Here we report a case of endometrial intraepithelial neoplasia in a transgender man taking testosterone.

Evaluation of patterns of progression on poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance in ovarian cancer: a cross-sectional study.

INTRODUCTION: Despite improvement in progression-free survival with poly (ADP-ribose) polymerase inhibitors (PARPi) as maintenance therapy for ovarian cancer, many patients will eventually progress on therapy. Oligoprogression is uniquely suited to considerations of local consolidation therapy in this setting, but not commonly used in ovarian cancer. In this study we evaluated the proportion of patients on PARPi maintenance who developed limited sites of disease, the location of progression, and their natural history. METHODS: From January 2006 to December 2020, natural language processing software (DEEP6AI) was used to identify 58 patients with ovarian cancer treated with PARPi maintenance after complete or partial response after surgery and platinum-based chemotherapy at our institution. Patients were assessed for presence and location of recurrence based on radiologic findings. RESULTS: The median patient age was 65 (IQR 57-71) years. Patients had a median of two lines of chemotherapy prior to starting PARPi. With a median follow-up of 48 (range 12-149) months, 32 (55%) patients had a recurrence on maintenance olaparib and 11 (34%) patients developed oligoprogression (≤3 sites). For the 11 patients with oligoprogression, three patients developed recurrence in one site, five in two sites, and three in three sites. The sites of oligoprogression were pelvic/periaortic nodal (27%), peritoneal (27%), liver (27%), lung/mediastinal (14%), and brain (5%). The median progression-free survival for the entire cohort was 6.0 months (95% CI 4.2 to 7.8); median overall survival was not met. There were no significant differences in overall survival (p=0.81) or progression-free survival (p=0.95) between patients with and without oligoprogression. CONCLUSIONS: One-third of patients on PARPi maintenance experienced oligoprogression defined as limited to ≤3 sites. These patients may benefit from local consolidation therapy. A larger dataset is needed to validate these findings to assess if trials investigating local therapy for these patients is of value.

Narcotics reduction, quality and safety in gynecologic oncology surgery in the first year of enhanced recovery after surgery protocol implementation.

OBJECTIVES: Enhanced Recovery After Surgery (ERAS) programs are mechanisms for achieving value-based improvements in surgery. This report provides a detailed analysis of the impact of an ERAS program on patient outcomes as well as quality and safety measures during implementation on a gynecologic oncology service at a major academic medical center. METHODS: A retrospective review of gynecologic oncology patients undergoing elective laparotomy during the implementation phase of an ERAS program (January 2016 through December 2016) was performed. Patient demographics, surgical variables, postoperative outcomes, and adherence to core safety measures, including antimicrobial and venous thromboembolism (VTE) prophylaxis, were compared to a historical patient cohort (January 2015 through December 2015). Statistical analyses were performed using t-tests, Wilcoxon rank sum tests, and Chi squared tests. RESULTS: The inaugural 109 ERAS program participants were compared to a historical patient cohort (n=158). There was no difference in BMI, race, malignancy, or complexity of procedure between cohorts. ERAS patients required less narcotics (70.7 vs 127.4, p=0.007, oral morphine equivalents) and PCA use (32.1% vs. 50.6%, p=0.002). Despite this substantial reduction in narcotics, ERAS patients did not report more pain and in fact reported significantly less pain by postoperative day 3. There were no differences in length of stay (5days), complication rates (13.8% vs. 20.3%, p=0.17) or 30-day readmission rates (9.5 vs 11.9%, p=0.54) between ERAS and historical patients, respectively. Compliance with antimicrobial prophylaxis was 97.2%. However, 33.9% of ERAS patients received substandard preoperative VTE prophylaxis. CONCLUSIONS: ERAS program implementation resulted in reductions in narcotic requirements and PCA use without changes in length of stay or readmission rates. Compliance should be diligently audited during the implementation phase of ERAS programs, with special attention to adherence to pre-existing core safety measures.

Phylogenomic evidence supports past endosymbiosis, intracellular and horizontal gene transfer in Cryptosporidium parvum.

BACKGROUND: The apicomplexan parasite Cryptosporidium parvum is an emerging pathogen capable of causing illness in humans and other animals and death in immunocompromised individuals. No effective treatment is available and the genome sequence has recently been completed. This parasite differs from other apicomplexans in its lack of a plastid organelle, the apicoplast. Gene transfer, either intracellular from an endosymbiont/donor organelle or horizontal from another organism, can provide evidence of a previous endosymbiotic relationship and/or alter the genetic repertoire of the host organism. Given the importance of gene transfers in eukaryotic evolution and the potential implications for chemotherapy, it is important to identify the complement of transferred genes in Cryptosporidium. RESULTS: We have identified 31 genes of likely plastid/endosymbiont (n = 7) or prokaryotic (n = 24) origin using a phylogenomic approach. The findings support the hypothesis that Cryptosporidium evolved from a plastid-containing lineage and subsequently lost its apicoplast during evolution. Expression analyses of candidate genes of algal and eubacterial origin show that these genes are expressed and developmentally regulated during the life cycle of C. parvum. CONCLUSIONS: Cryptosporidium is the recipient of a large number of transferred genes, many of which are not shared by other apicomplexan parasites. Genes transferred from distant phylogenetic sources, such as eubacteria, may be potential targets for therapeutic drugs owing to their phylogenetic distance or the lack of homologs in the host. The successful integration and expression of the transferred genes in this genome has changed the genetic and metabolic repertoire of the parasite.