Olga Grechukhina

Circulating microRNAs as potential biomarkers for endometriosis

OBJECTIVE To evaluate whether microRNAs (miRNAs) associated with endometriosis are detectable in the circulation and could serve as potential noninvasive biomarkers for endometriosis. DESIGN Case-control study. SETTING University hospital. PATIENT(S) Twenty-four women with endometriosis and 24 women without the disease (controls). INTERVENTION(S) Serum samples collected from women undergoing laparoscopy for endometriosis and other benign gynecologic disease. MAIN OUTCOME MEASURE(S) Total RNA extracted from serum and quantitative reverse-transcription polymerase chain reaction to determine levels of miRNA let-7a-f and miR-135a,b. RESULT(S) The levels of circulating let-7b and miR-135a were statistically significantly decreased in women with endometriosis compared with controls, and let-7d and 7f showed a trend toward down-regulation. Let-7b expression strongly correlated with serum CA-125 levels and showed the highest area under the curve of 0.691. When the patients were analyzed according to phase of the menstrual cycle, the expression of let-7b, 7c, 7d, and 7e was statistically significantly lower in the women with endometriosis during the proliferative phase. Using a logistic regression model, we evaluated the diagnostic power of differently expressed miRNAs; the combination of let-7b, let-7d, and let-7f during the proliferative phase yielded the highest area under the curve value of 0.929 in discriminating endometriosis from controls. CONCLUSION(S) Several circulating miRNAs are differentially expressed in the sera of women with endometriosis compared with controls. The combination of serum let-7b, 7d, and 7f levels during the proliferative phase may serve as a diagnostic marker for endometriosis.

Global Gene Expression Profiling of Proliferative Phase Endometrium Reveals Distinct Functional Subdivisions

The human endometrium follows a predictable pattern of development during the proliferative phase. Endometrial thickness increases after day 3 and then plateaus at days 9 to 10 of the menstrual cycle despite continued high serum levels of estrogen. We hypothesized that proliferative phase endometrium undergoes more than simple estrogen responsive growth, rather it is characterized by complex time-dependent functional activities reflected in differential gene expression. Nine endometrial RNA samples from healthy participants were subjected to microarray analysis and 15 samples were used for quantitative real-time polymerase chain reaction. The samples were divided into early, mid, or late proliferative phase. The early proliferative phase showed higher expression of genes including transforming growth factor β2, chemokine (C-C motif) ligand 18 (CCL18), and metallothionein 2A. The mid-proliferative phase was characterized by higher expression of heat shock proteins and implantation-associated genes including Indian hedgehog, secreted frizzled protein 4, and progesterone receptor. In the late proliferative phase, we identified increased angiotensin II receptor, type 2 and large decrease in expression of genes related to natural killer (NK) cell function. We demonstrate a unique gene expression signature at distinct time points within the proliferative phase. The early proliferative phase is characterized by tissue remodeling, angiogenesis, and modulation of inflammation; the mid-proliferative phase is characterized not only by proliferation in response to estrogens but also marks the onset of expression of genes required for endometrial receptivity and a dampening of estrogen responsiveness. In the late proliferative phase, changes in immune function and NK cells predominate. The proliferative phase is not simply a uniform period of estrogen responsive endometrial growth that can be considered as a single experimental time point when evaluating endometrial development; rather the proliferative phase is complex with differing functions and patterns of gene expression.

Challenging Case of Postmenopausal Bleeding and Complete Urogenital Duplication

Patient: Female, 58 Final Diagnosis: Congenital duplication of genitourinary system Symptoms: — Medication: — Clinical Procedure: Laparoscopic hysterectomy Specialty: Obstetrics and Gynecology Objective: Congenital defects/diseases Background: Müllerian duct anomalies represent a wide spectrum of congenital abnormalities ranging from simple uterine anomalies to more complex multisystem derangements. Complete duplication of uterus, cervix, and vagina may be associated with urologic and caudal gastrointestinal malformations. Case Report: We present a case report detailing the management of a morbidly obese patient with postmenopausal bleeding and thickened endometrial stripe who had a very rare condition of pelvic organ duplication, including 2 hemiuteri, 2 vaginas, 2 hemibladders, and 2 each of ovaries, fallopian tubes, kidneys, and ureters. Laparoscopic hysterectomy was complicated by difficulties understanding urinary system anatomy requiring intraoperative urology consultation and imaging. Conclusions: Management of patients with urogenital duplication and abnormal uterine bleeding requires a thorough understanding of possible associated malformations. Thorough preoperative evaluation, careful surgical exploration, and multidisciplinary approach may be necessary to avoid urologic injury in such patients.

Endometrial Carcinoma in a 26-Year-Old Patient with Bardet-Biedl Syndrome

Background Bardet-Biedl Syndrome (BBS) is a rare genetic condition characterized by cognitive impairment, dysmorphism, central obesity, and diabetes mellitus, among other abnormalities. Although some of these characteristics are known independent risk factors for endometrial cancer and its precursors, the association between BBS and endometrial cancer is underreported. Case We present the case of a 26-year-old patient with BBS and clinical signs of hyperestrogenism who presented with abnormal uterine bleeding and was diagnosed with endometrioid adenocarcinoma. She ultimately underwent definitive surgical treatment with hysterectomy and bilateral salpingectomy. Conclusions This is one of only a few reports in the literature describing the association of BBS and endometrioid endometrial adenocarcinoma. Given the association of BBS with risk factors for hyperestrogenism such as truncal obesity, hyperinsulinemia, and ovulatory dysfunction, providers should have increased suspicion for endometrial cancer in young patients with BBS and abnormal uterine bleeding.

A Novel Approach to Serial Amnioinfusion in a Case of Premature Rupture of Membranes Near the Limit of Viability

Prelabor rupture of the membranes (PROM) near the limit of viability is associated with significant risks for both mother and fetus. Preterm labor, intra-amniotic infection, and placental abruption are the immediate risks to the pregnancy; however, the fetus incurs additional risks related to the sequela of persistent oligohydramnios. Transabdominal intra-amniotic infusions have been studied. Results, suggesting that this intervention may prolong the latency period, and potentially, decrease pulmonary hypoplasia in surviving neonates without evidence of increasing risk of intra-amniotic infection. To our knowledge, the use of antibiotic-infused fluid has not been reported in this clinical scenario. Therefore, we present a case of a patient with PROM before the limit of viability who underwent serial transabdominal amnioinfusions with oxacillin-containing normal saline, which resulted in membrane resealing and neonatal survival with no additional maternal morbidity.

Unusual presentation of a rectovestibular fistula as gastrointestinal hemorrhage in a postmenopausal woman.

Background. Anorectal malformations (ARMs) are extremely rare and are usually identified neonatally. It is unusual for these cases to present in the postmenopausal period. This case report describes a postmenopausal patient with ARM and rectovaginal hemorrhage. Case. An 86-year-old, gravida 11, para 9, presented to the emergency department complaining of profuse postmenopausal vaginal bleeding. Her gynecologic history was significant only for an unclear history of an anal abnormality that was noted at birth. Speculum examination revealed profuse rectal bleeding from a rectovestibular fistula exterior to her hymenal ring. Colonoscopic examination revealed severe diverticular disease. Conclusion. This patient was born with an imperforate anus which resolved as rectovestibular fistula and ectopic anus. This case presents a rare clinical circumstance which integrates the fields of obstetrics, gynecology, gastroenterology, and embryology alike.