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Heatmap of protein functions

The human microbiome has been strongly correlated with disease pathology and outcomes, yet remains relatively underexplored in patients with malignant endometrial disease. In this study, vaginal microbiome samples were prospectively collected at the time of hysterectomy from 61 racially and ethnically diverse patients from three disease conditions: (i) benign gynecologic disease (controls, n = 11), (ii) low-grade endometrial carcinoma (n = 30), and (iii) high-grade endometrial carcinoma (n = 20). Extracted DNA underwent shotgun metagenomics sequencing, and microbial α and β diversities were calculated. Hierarchical clustering was used to describe community state types (CST), which were then compared by microbial diversity and grade. Differential abundance was calculated, and machine learning utilized to assess the predictive value of bacterial abundance to distinguish grade and histology. Both α- and β-diversity were associated with patient tumor grade. Four vaginal CST were identified that associated with grade of disease. Different histologies also demonstrated variation in CST within tumor grades. Using supervised clustering algorithms, critical microbiome markers at the species level were used to build models that predicted benign versus carcinoma, high-grade carcinoma versus benign, and high-grade versus low-grade carcinoma with high accuracy. These results confirm that the vaginal microbiome segregates not just benign disease from endometrial cancer, but is predictive of histology and grade. Further characterization of these findings in large, prospective studies is needed to elucidate their potential clinical applications.Significance:The vaginal microbiome reliably segregates not just benign gynecologic condition from endometrial cancer, but also predicts cancer grade and histology. Patterns of microbial abundance and gene expression should be increasingly considered as a factor in the evolution of precision medicine approaches, especially as they relate to cancer screening, disease pathogenesis, and patient-centered outcomes.

Heatmap of abundance values

Additional statistical methods

Biomarker discovery by histology

Individual Specimen Reads

Analysis of Confounders

Functional pathway analysis

Microbial alpha diversities

Microbial abundance by histotype

The human microbiome has been strongly correlated with disease pathology and outcomes, yet remains relatively underexplored in patients with malignant endometrial disease. In this study, vaginal microbiome samples were prospectively collected at the time of hysterectomy from 61 racially and ethnically diverse patients from three disease conditions: (i) benign gynecologic disease (controls, n = 11), (ii) low-grade endometrial carcinoma (n = 30), and (iii) high-grade endometrial carcinoma (n = 20). Extracted DNA underwent shotgun metagenomics sequencing, and microbial α and β diversities were calculated. Hierarchical clustering was used to describe community state types (CST), which were then compared by microbial diversity and grade. Differential abundance was calculated, and machine learning utilized to assess the predictive value of bacterial abundance to distinguish grade and histology. Both α- and β-diversity were associated with patient tumor grade. Four vaginal CST were identified that associated with grade of disease. Different histologies also demonstrated variation in CST within tumor grades. Using supervised clustering algorithms, critical microbiome markers at the species level were used to build models that predicted benign versus carcinoma, high-grade carcinoma versus benign, and high-grade versus low-grade carcinoma with high accuracy. These results confirm that the vaginal microbiome segregates not just benign disease from endometrial cancer, but is predictive of histology and grade. Further characterization of these findings in large, prospective studies is needed to elucidate their potential clinical applications. Significance: The vaginal microbiome reliably segregates not just benign gynecologic condition from endometrial cancer, but also predicts cancer grade and histology. Patterns of microbial abundance and gene expression should be increasingly considered as a factor in the evolution of precision medicine approaches, especially as they relate to cancer screening, disease pathogenesis, and patient-centered outcomes.

Objective Mutations in the MAP kinase pathway (KRAS, NRAS, BRAF) are common in low grade serous ovarian carcinoma (LGSOC). The effect of these and other mutations on RNA transcription in this disease is poorly understood. Our objective was to describe patterns of somatic mutations and gene transcription in a racially diverse population with LGSOC. Methods Utilizing an institutional tumor registry, patients with LGSOC were identified and charts were reviewed. RNA was extracted from available tumor tissue. Commercial tumor profiling results were analyzed with PanCancer pathway nanoString mRNA expression data. Along with nanoString n-Solver software, Chi-squared, Fishers Exact, and Cox proportional hazards models were used for statistical analysis, with significance set at p Results 39 patients were identified—20% Black, 43% Hispanic, and 36% non-Hispanic White. 18 patients had commercial somatic DNA test results, and 23 had available tumor tissue for RNA extraction and nanoString analysis. The most common somatic alterations identified was KRAS (11 patients, 61%), followed by ERCC1 and TUBB3 (9 each, 50%). KRAS mutations were less common in smokers (14.3% vs 90.9%, p = 0.002). RNA expression analysis demonstrated a greater than two-fold decrease in expression of HRAS in tumors from older patients (p = 0.04), and a greater than two-fold decrease in the expression of HRAS in recurrent tumors (p = 0.007). No significant differences were seen in somatic testing results, RNA expression analysis, or progression free survival between different racial and ethnic cohorts. Conclusions Somatic deficiencies in ERCC1, TUBB3, and KRAS are common in LGSOC in a population of minority patients. HRAS demonstrates decreased expression in tumors from older patients and recurrent tumors.

The Singapore flap, which is a pedicled pudendal fasciocutaneous flap from the thigh, is used for vaginal reconstruction in the case of vaginal agenesis, perineal wound closure, rectovaginal fistula repair, and disorders of sexual differentiation. It may also be used to reconstruct the vagina following pelvic exenteration in the case of gynecologic malignancy. Possible complications include flap loss or necrosis, wound dehiscence, neovaginal stenosis or prolapse, infection, hair growth, and dyspareunia.

While the majority of studies regarding the health benefits from human papillomavirus (HPV) vaccination have focused on cervical neoplasia and cancer, few have investigated how the epidemiology of vaginal and vulvar disease may be affected. To better understand how occurrence rates for vaginal and vulvar neoplasias and carcinomas may change in the future, we must have an understanding of the overall disease prevalence within a given population, the efficacy of vaccination and the proportion of cases attributable to HPV types administered in the vaccine. In this review, we will examine basic HPV epidemiology and prevalence, the molecular transformation events carried out by HPV oncoproteins, and clinical trials monitoring HPV-induced disease of the female genital tract. While precise projections of exactly how vaginal and vulvar disease prevalence will change with vaccination will require more studies, the preliminary data are promising.

Cystic adenomyosis is a rare form of adenomyosis. Presently, these cysts are generally considered to be of a benign nature and result from cyclical response to menstrual dynamics.A 31-year-old, African-American female presented for a second opinion with a chief complaint of pelvic pain. She had recently undergone an exploratory laparoscopy with findings suggestive of endometriosis. She was never pregnant and had been taking oral contraceptive pills for over 3 months with little relief This patient had no history of uterine surgery. Pelvic ultrasound performed after her surgery revealed a cystic structure, homogeneously echogenic in the anterior corpus of the uterus, measuring 2.7 x 2.4 x 3.5 cm. This structure appeared consistent with an adenomyotic cyst. The patient's symptoms improved after the transvaginal aspiration, and she no longer required narcotics.Of all the possibilities considered, this cyst most closely resembled an adenomyotic cyst in its clinical presentation, location within the myometrium and gross appearance of the chocolate cyst fluid. Imaging is key in distinguishing this process from other congenital and acquired gynecologic entities. Awareness of this condition is important for timely and accurate diagnosis followed by appropriate intervention.

Fibroids are the most common gynecologic tumors. Our case discusses the outcome of a 47-year-old woman who presented to our clinic with cachexia, and a giant abdominal mass. An initial diagnostic imaging workup consisted of X-Ray, CT, and ultrasound and indicated a possible diagnosis of leiomyosarcoma. However, after surgical evaluation, she was diagnosed pathologically with an atypical presentation of a uterine leiomyoma. Our case reviews the epidemiology and presentation of both pathologies, along with the imaging workup, and the operative correlation in our patient.

According to the prescribing information, pegfilgrastim should not be administered within 14 days prior to, or within 24 hours after, the administration of cytotoxic chemotherapy. However, few data exist to support this recommendation. A single-institution retrospective review was conducted of all patients with ovarian or primary peritoneal cancer who received prophylactic pegfilgrastim on the same day as myelosuppressive chemotherapy from May 2003 to June 2006. Forty-six patients were treated for the following malignancies: 35 (76%) epithelial ovarian, 6 (13%) primary peritoneal, and 5 (11.0%) ovarian germ cell or stromal cell carcinoma. All patients met the current guidelines of using colony-stimulating factors for prophylaxis against febrile neutropenia. A total of 269 cycles of chemotherapy were administered. All patients received pegfilgrastim within 1 hour of the completion of chemotherapy administration. Grade 1 or 2 neutropenia developed in 10 cycles (3.7%), and the mean absolute neutrophil count was 4926/uL (range, 1,293-24,300). No patients had febrile neutropenic episodes, hospitalizations, or antibiotic use secondary to neutropenia, nor did they have dose reductions or chemotherapy delays due to neutropenia. Administration of pegfilgrastim on the same day as myelosuppressive chemotherapy in patients with ovarian or primary peritoneal cancer may be determined to be a convenient, safe, and effective approach.

Objectives This study was designed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of weekly docetaxel with concurrent radiotherapy (RT) for the primary treatment of locally advanced squamous cell carcinoma of the cervix. Methods Eligible patients included those with locally advanced squamous cell cervical cancer without para-aortic lymph node involvement. Docetaxel dose levels were 20 mg/m 2 , 30 mg/m 2 and 40 mg/m 2 given intravenously weekly for 6 cycles. Three patients were to be treated at each dose level and 6 to receive the MTD. Results Fifteen patients completed 4–6 cycles of chemotherapy. One of three patients experienced 2 delayed grade 3 severe adverse events (SAE) at the 20 mg/m 2 dose level consisting of colonic and ureteral obstruction. At the 30 mg/m 2 dose level, 1/4 patients had a probable treatment-related celiotomy due to obstipation and a necrotic tumor. Of the 8 patients treated at the 40 mg/m 2 dose level, 1 experienced grade 3 pneumonitis, likely treatment related. Overall, 10/15 (67%) experienced grade 1 or 2 diarrhea, 6 had grade 2 hematologic toxicity, and 2 had grade 2 hypersensitivity. 10 of 16 patients (67%) had no evidence of disease with follow-up ranging from 10–33 months (average 23 months). Conclusions The recommended phase II dose of docetaxel administered weekly with concurrent radiotherapy for locally advanced squamous cell carcinoma of the cervix is 40 mg/m 2 .