Benign Uterine Neoplasm as a Cause of Prepubertal Bleeding.

BACKGROUND: Vaginal bleeding in the prepubertal child has several etiologies, including structural anomalies, endocrinologic dysfunction, infection, trauma, foreign body, and hematologic disorders. CASE: An 8-year-old premenarcheal girl presented with vaginal bleeding. On ultrasound, she was found to have an intramural hyperechogenic mass in the left uterine fundus. This was biopsied and showed smooth muscle. She was subsequently started on a GnRH agonist to suppress bleeding and has since been followed with serial ultrasounds. We have 6 years of follow-up imaging showing a presumed adenomyoma versus fibroid that has been stable in size. SUMMARY AND CONCLUSION: We present a novel case of adenomyosis presenting as prepubertal bleeding. Pelvic imaging is prudent to exclude structural etiologies as the cause of prepubertal vaginal bleeding.

Differentiating mouse embryonic stem cells express markers of human endometrium.

BACKGROUND: Modeling early endometrial differentiation is a crucial step towards understanding the divergent pathways between normal and ectopic endometrial development as seen in endometriosis. METHODS: To investigate these pathways, mouse embryonic stem cells (mESCs) and embryoid bodies (EBs) were differentiated in standard EB medium (EBM). Immunofluorescence (IF) staining and reverse-transcription polymerase chain reaction (RT-PCR) were used to detect expression of human endometrial cell markers on differentiating cells, which were sorted into distinct populations using fluorescence-activated cell sorting (FACS). RESULTS: A subpopulation (50%) of early differentiating mESCs expressed both glandular (CD9) and stromal (CD13) markers of human endometrium, suggestive of a novel endometrial precursor cell population. We further isolated a small population of endometrial mesenchymal stem cells, CD45-/CD146+/PDGFR-ß+, from differentiating EBs, representing 0.7% of total cells. Finally, quantitative PCR demonstrated significantly amplified expression of transcription factors Hoxa10 and Foxa2 in CD13+ EBs isolated by FACS (p = 0.03). CONCLUSIONS: These findings demonstrate that mESCs have the capacity to express human endometrial cell markers and demonstrate potential differentiation pathways of endometrial precursor and mesenchymal stem cells, providing an in vitro system to model early endometrial tissue development. This model represents a key step in elucidating the mechanisms of ectopic endometrial tissue growth. Such a system could enable the development of strategies to prevent endometriosis and identify approaches for non-invasive monitoring of disease progression.

Use of norethindrone acetate alone for postoperative suppression of endometriosis symptoms.

STUDY OBJECTIVE: To evaluate the efficacy and tolerability of norethindrone acetate (NA) as single-agent hormonal therapy for suppression of endometriosis symptoms in adolescents and young adults. DESIGN: Retrospective study. SETTING: Two academic medical centers. PARTICIPANTS: A keyword search using the query 'NA' was applied to the electronic medical records of all women treated by one gynecologist (M.R.L.) from 1992 to 2010. IRB-approved chart review was then conducted on the index records. INTERVENTIONS: Continuous treatment with NA (5-15 mg daily). MAIN OUTCOME MEASURES: Postoperative bleeding and pain scores; adverse effects. RESULTS: One hundred and ninety-four patients with surgically diagnosed endometriosis initiated NA postoperatively during the study period. Median patient age was 18.9 years. 92.2% of patients had stage 1 or 2 disease, and distribution was similar among those excluded. Median pain scores decreased from 5 at NA initiation to 0 at follow-up (P = .0001) and bleeding scores from 2 to 0, respectively (P = .001) for all stages of endometriosis. Post-NA bleeding scores were improved regardless of prior hormonal regimen, and post-NA pain scores improved in all patients except for those previously prescribed GnRH-agonist plus add-back. Most patients (55.2%) did not report any side effects. The most common adverse effect was weight gain (16.1%), with a mean increase in BMI of 1.2 ± 1.6 kg/m(2) at 12 months. CONCLUSION: NA alone is a well-tolerated, effective option to manage pain and bleeding for all stages of endometriosis. Among those on prior hormonal therapy, symptoms improved after NA initiation.

Recurrent bilateral serous cystadenomas in a premenarchal girl: a case report and literature review.

BACKGROUND: Ovarian serous cystadenomas are rare in children. No case of recurrence after surgical resection in a premenarchal girl has been published. CASE: An 8-year-old presented with abdominal pain and ultrasound showed bilateral ovarian cystic masses with normal clinical and laboratory exam. Cystectomies were performed revealing serous cystadenomas. Ten months later, her pain returned and ultrasound showed new cysts. Persistence of cysts and symptoms required repeat surgery with the same pathology. SUMMARY AND CONCLUSION: Premenarchal girls with ovarian cystic masses require surgical intervention in cases of persistent symptoms, uncertain diagnosis, or concern for ovarian torsion. With reassuring imaging and tumor markers, conservation of the ovary can be achieved with cystectomy alone. Ultrasound follow-up is recommended after surgical resection until bimanual exam can be performed.

The effect of combined surgical-medical intervention on the progression of endometriosis in an adolescent and young adult population.

STUDY OBJECTIVE: To evaluate the effect of combined surgical-medical treatment on endometriosis progression in adolescents as measured by disease stage. DESIGN: Retrospective chart review. SETTING: Two academic medical centers. PARTICIPANTS: Sequential cases of young women identified on chart review with chronic pelvic pain unresponsive to dysmenorrheal treatment who underwent initial laparoscopy for diagnosis and surgical destruction of endometriosis. All patients were then treated with standard continuous medical therapy. Patients with exacerbation of pain on anti-endometriosis medical therapy who elected a subsequent laparoscopic procedure were eligible for this study. INTERVENTION: Retrospective chart review MAIN OUTCOME MEASURES: Endometriosis stage and adhesions at subsequent laparoscopy as compared to the initial surgical procedure. RESULTS: 90 patients met inclusion criteria. Eligible patients were 12 to 24 years of age at the time of the initial laparoscopy. The median endometriosis stage at first and second laparoscopy was I. No stage change was observed in 70% of patients, 19% improved by one stage, 1% improved by two stages, and 10% worsened by one stage. Regardless of initial stage, a trend toward disease progression was not observed. There was a significant likelihood for stage improvement at second laparoscopy, with those initially diagnosed as stage II or III most likely to exhibit improvement. CONCLUSIONS: Based on the concept that endometriosis can be progressive, these data suggest that combined surgical-medical management retards disease progression in adolescents and young adults.

Thrombocytosis associated with malignant ovarian lesions within a pediatric/adolescent population.

STUDY OBJECTIVE: To determine if there is an association between pediatric ovarian malignancies and elevated platelet counts: DESIGN: Retrospective chart review. SETTING: Large referral children's hospital. PARTICIPANTS: 154 patients taken to the operating room between February 1993 and February 2006 with an adnexal mass where ovarian tissue was submitted for pathological analysis. MAIN OUTCOME MEASURES: The principle outcome was the presence of ovarian malignancy. RESULTS: We found that there is an increase in thrombocytosis among individuals with ovarian malignancy, with as high as 33% of those with ovarian germ cell tumors demonstrating preoperative thrombocytosis. CONCLUSION: These results suggest that thrombocytosis may be a useful marker for ovarian malignancy in this population. Further studies will be needed to determine if there is any prognostic value to thrombocytosis among these patients, with a potential value for counseling and future intervention based on these findings.

High risk of infertility and long term gonadal damage in males treated with high dose cyclophosphamide for sarcoma during childhood.

BACKGROUND: Therapy with alkylating agents, such as cyclophosphamide, can be associated with irreversible gonadal toxicity in male survivors of adult cancer. To the authors's knowledge the effect of high dose therapy with cyclophosphamide during childhood on adult testicular reproductive and endocrine function has not been established. METHODS: Gonadal function was studied in 17 adult male survivors of childhood sarcomas treated with high dose pulse cyclophosphamide therapy as part of a VAC (vincristine, actinomycin, and cyclophosphamide) or Adria-VAC (doxorubicin, vincristine, actinomycin, and cyclophosphamide) chemotherapy regimen. Patients answered a questionnaire concerning sexual functioning and underwent a comprehensive physical examination, semen analysis, and hormonal evaluation. RESULTS: Of the 17 males who underwent semen analysis, 10 (58.8%) had azoospermia, 5 (29.4%) had oligospermia, and only 2 (11.8%) were found to have a normal sperm count. All patients treated prior to the onset of puberty had an abnormal semen analysis. The 2 patients with normal sperm counts received the lowest doses of cyclophosphamide (< 7.5 g/m(2)). The baseline follicle-stimulating hormone level was elevated in only 10 of 14 patients with abnormal sperm counts (71.4%). Testosterone levels were normal in 15 of 16 patients (93.8%); however, the baseline luteinizing hormone (LH) level was elevated in 6 of 15 patients with normal testosterone levels (40%). Gonadotropin-releasing hormone-stimulated LH levels were > 3 times that of baseline in 13 of /14 patients (92.9%), suggesting some degree of Leydig cell insufficiency. CONCLUSIONS: The results of the current study show a high risk of gonadal dysfunction in men exposed to cyclophosphamide during childhood as part of a VAC/Adria-VAC chemotherapy regimen. Exposure prior to puberty was not found to be protective, and the risk of infertility appeared to increase with higher doses of therapy. To the authors' knowledge the clinical significance of impaired Leydig cell function beginning at a young age is unknown and merits further study.

Conservative management of bilateral asynchronous adnexal torsion with necrosis in a prepubescent girl.

Conservative management of ovarian torsion consisting of detorsion and surgical stabilization of the involved ovary, and possibly including the uninvolved ovary, has been described in the adult population. A 6-year-old girl with a history of prior ovarian torsion resulting in oophorectomy presented with 72 hours of intermittent abdominal pain, anorexia, and 1 episode of vomiting. The patient had torsion of her remaining ovary diagnosed surgically and was managed with detorsion and oophoropexy, despite the severely necrotic appearance of the ovarian tissue. Postoperative serial ultrasound scans confirmed the viability and position of the ovary. In the prepubertal girl, ovaries may torse despite the absence of enlarging lesions such as tumors or cysts. To maximize the potential success of conservative therapy, torsion always must be included in the differential diagnosis of abdominal pain. Surgical management should attempt to salvage the torsed ovary, despite possible necrotic appearance, and also consider interventions to prevent recurrence, because bilateral torsion is a rare but potentially devastating complication.

Three years of a clinical practice guideline for uncomplicated pelvic inflammatory disease in adolescents.

PURPOSE: To study the effect of continued use of a clinical practice guideline (CPG) on the course of admissions for uncomplicated pelvic inflammatory disease (PID) over 3 consecutive fiscal years (FY). METHODS: Medical charts, computerized laboratory records, and hospital charge data were reviewed for 165 consecutive inpatient admissions of adolescents meeting clinical criteria for PID during FY 1994, 1995, and 1996. Data were analyzed to compare demographics, clinical variables, length of stay (LOS), and hospital charges (total, nursing, and pharmacy) across the three FYs. RESULTS: Of admissions for clinical PID, 65% had a discharge diagnosis of PID. Of those, 90% were uncomplicated PID. Among admissions with a discharge diagnosis of uncomplicated PID, reductions were seen in mean LOS (3.75 days in FY 1994 vs. 3.24 days in FY 1995 vs. 3.08 days in FY 1996; p =.047), proportion of admissions lasting longer than 3 days (48% vs. 24% vs. 20%; p < or =.022), and mean pharmacy charge ($946 vs. $806 vs. $731; p =.002). For all admissions to CPG, mean LOS, proportion of prolonged admissions, and mean total and pharmacy charges also decreased over the first 2 years but increased in FY 1996. More patients in FY 1996 met the three major clinical criteria plus at least one additional criterion (76% in FY 1996 vs. 26% in FY 1994 and 53% in FY 1995; p <.0005) and had pelvic ultrasounds (80% in FY 1996 vs. 56% in FY 1994 and 45% in FY 1995; p < or =.001) than in other FYs. CONCLUSIONS: Continued use of a CPG can reduce hospital LOS, charges, and prolonged admissions of adolescents with uncomplicated PID. Over 3 years, variations in clinical practice such as admitting sicker patients may attenuate the effect of the CPG.

Surgicel in the management of labial and clitoral hood adhesions in adolescents with lichen sclerosus.

STUDY OBJECTIVE: Lichen sclerosus (LS) is an inflammatory dermatosis of the vulva with potentially destructive consequences to the young woman's perineum. Long-term sequelae include atrophy of the labia minora, scarring of the clitoral hood, and labial and/or clitoral hood adhesions. This study aims to find techniques for preventing these devastating effects. PARTICIPANTS: Three young women, ages 14 and 15 years, with a long history of lichen sclerosus and labial adhesions, presented with recurrent labial and periclitoral adhesions. Increasing pain prior to presentation, exquisite enough to inhibit even walking, necessitated urgent operative intervention. Scarring of the clitoral hood with an area of firmness beneath the scarring was present. Sharp dissection of the clitoral hood was performed with the entrapped keratinaceous debris and hair expressed. The adherent labia were separated. Surgicel, oxidized regenerated cellulose gauze (Johnson & Johnson, Arlington, TX), was sutured to the exposed clitoral hood and labial surfaces with vicryl suture. Complete dissolution of the Surgicel occurred between postoperative day 4-6 without recurrence of adhesions. One-year follow-up did not reveal any evidence of recurrence in any of the three patients. CONCLUSION: The recurrence of labial and clitoral hood adhesions in young women with a history of LS was prevented for at least 1 year by surgical lysis and application of Surgicel to the affected area. This technique has prevented the recurrence during the interval when these surfaces are at highest risk of re-agglutination.

Microlaparoscopy with conscious sedation in adolescents with suspected pelvic inflammatory disease.

STUDY OBJECTIVE: To develop a protocol for emergency department microlaparoscopy with conscious sedation in adolescents with clinically suspected pelvic inflammatory disease (PID), and to evaluate the feasibility and tolerability of microlaparoscopy in this population. DESIGN: Prospective study involving adolescents and young adults age 13 to 24 meeting clinical criteria for uncomplicated PID. Laparoscopy subjects underwent microlaparoscopy in the Children's Hospital Emergency Department (ED) and comparison subjects were admitted for treatment of PID. Chi-square, Mann-Whitney U tests, Wilcoxon Rank Sum tests, and repeated measures of analysis of variance (MANOVA) were used for analysis. RESULTS: Twenty-four patients were enrolled: 6 laparoscopy subjects and 18 comparison subjects. Laparoscopy and comparison subjects did not differ with respect to age, mean white blood cell (WBC) count, mean temperature, or mean erythrocyte sedimentation rate. Mean surgical induction time was 13.5 minutes, operative time 19.0 minutes, and total procedure time 32.5 minutes. Mean requirement for midazolam was 2.8 mg and for fentanyl 225 microg. Pain assessment over the first 90 minutes did not differ significantly between laparoscopy and comparison subjects. Four of 6 laparoscopy subjects (67%) and 10 of 18 comparison subjects (56%) were diagnosed with PID (p = NS). CONCLUSIONS: ED microlaparoscopy appears to be feasible, safe, and well tolerated in this small sample of adolescents and young adults with suspected PID.

Developmental abnormalities of the female reproductive tract.

Developmental abnormalities of the female reproductive tract are a group of heterogeneous anomalies that may also affect other organ systems. Our review outlines the diverse abnormalities, etiologies, modes of diagnosis, and treatment options currently available.

Endometriosis in adolescents. Incidence, diagnosis and treatment.

OBJECTIVE: To review the incidence and diagnosis of endometriosis in adolescents and to evaluate the surgical and medical treatment options for this special population. STUDY DESIGN: Literature research. RESULTS: Endometriosis is the most common cause of chronic pelvic pain in adolescents, affecting up to 70% of girls with chronic pelvic pain unresponsive to medical management. There may be a natural progression of endometriosis from atypical lesions in adolescents to classic lesions in adults. CONCLUSION: Endometriosis should be strongly suspected in adolescent girls with chronic pelvic pain unresponsive to oral contraceptives and nonsteroidal antiinflammatory drugs. Initial management of endometriosis involves surgical resection or destruction at the time of diagnosis followed by medical management with continuous oral contraceptives. Gonadotropin-releasing hormone agonists should be considered for adolescents over 16 years of age who have completed pubertal maturation.

Pelvic pain.

Pelvic pain is a common symptom in the adolescent female. Acute pain may represent a life-threatening situation and torsion, ectopic pregnancy, and PID must be considered. For the young patient who presents with chronic pelvic pain, a multidisciplinary approach is essential to facilitate diagnosis and management. Whenever possible, organic disease such as endometriosis, adhesions, and obstructive malformations should be identified and treated as indicated. Developing a treatment team, recognizing psychosocial and environmental factors, and encouraging long-term relationships are critical components in the care of these patients and in the prevention of recurrent symptom formation and future disability.

Vulvar disorders in adolescents.

Bacterial and fungal vulvitis, dermatitis, inflammatory dermatoses, secondary drug reactions, viral infections, and a variety of vulvar tumors can all present as primary vulvar problems in adolescents. In addition, systemic disease can present with vulvar involvement. These disorders can be extremely anxiety-provoking in adolescent females who are dealing with issues surrounding self-image, physical maturation, and sexuality. A detailed history and physical exam can provide many clues to the underlying problem, but sometimes a biopsy is necessary to establish a diagnosis. Consultations from other services, such as dermatology or infectious diseases, can be very helpful. The best approach involves a combination of empathetic reassurance, careful diagnosis, and successful treatment. In order to facilitate optimal care of adolescents with vulvar disorders, a comprehensive review of the literature is presented.

Obstructive anomalies of the female reproductive tract.

Obstructive anomalies of the female reproductive tract preclude the outflow of menstruation and may allow the collection of blood in the uterus and/or vagina and increase the likelihood of retrograde flow. These conditions occur in young women and may result in pelvic masses, endometriosis and/or pain. In addition, the long-term sequelae of endometriosis may influence fertility. Pediatricians, primary care physicians and gynecologists need to maintain a high index of suspicion in order to aggressively diagnose these congenital anomalies in young adolescents. In order to maintain this vigilance and assist in maintaining future fertility, it is important to review the embryologic sources of these anomalies, understand the modes of diagnosis and recognize the treatment options currently available.

Limitations of the medical evaluation for child sexual abuse.

The purpose of this review is to highlight the inherent difficulties that a clinician faces during the evaluation of child sexual abuse cases. Each component of the medical evaluation has its own unique problems. Some of them are caused by the nature of the abusive relationship, while others are the result of the children's limited verbal skills. Readers should be aware of these limitations as they formulate an opinion at the conclusion of the examination.