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.

Association between the Absolute Baseline Lymphocyte Count and Response to Neoadjuvant Platinum-based Chemotherapy in Muscle-invasive Bladder Cancer.

AIMS: Platinum-based neoadjuvant chemotherapy (NAC) improves overall survival in muscle-invasive bladder cancer (MIBC). A pathological complete response (pCR) at radical cystectomy after NAC is associated with better overall survival, but there are no established predictive biomarkers of response to NAC in MIBC. The aim of this study was to find laboratory variables associated with pCR following NAC. MATERIALS AND METHODS: We carried out a retrospective review of MIBC patients treated with NAC followed by radical cystectomy at the Sheba Medical Center between 2005 and 2015. Overall survival was calculated using the Kaplan-Meier product-limit method and compared between patients who achieved or did not achieve pCR using the Log-rank test. Baseline and pre-surgery laboratory values were collected and compared between patients who subsequently achieved pCR and those who did not using logistic regression. RESULTS: Fifty-eight patients underwent radical cystectomy after NAC, with a median follow-up of 32 (range 4.8-111.4) months from diagnosis. Of 55 patients with documented pathological outcome on radical cystectomy, 17 (31%) achieved pCR (complete responders). Of the 15 complete responders with follow-up data, 13 (87%) were still alive at time of last follow-up for this study (July 2015). Patients who did not achieve pCR had a significantly worse overall survival than complete responders (P = 0.0007). The baseline lymphocyte count, neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were significantly associated with response (P = 0.037, P = 0.045, P = 0.042, respectively) on univariate analysis, whereas baseline albumin, haemoglobin, neutrophils, platelets and the total white blood count were not significantly associated with response. Lymphocyte counts were significantly higher in responders than non-responders throughout three time points (P = 0.003 using a generalised linear mixed model). CONCLUSIONS: A high baseline level of lymphocytes is associated with the achievement of pCR at radical cystectomy after NAC, which, in turn, is associated with a significantly longer overall survival. Our results suggest that chemosensitivity in MIBC is associated with lymphocyte count.

Acerca del yo corporal como objeto interno / On the body ego as internal object

La autora pretende establecer una distinción entre la imagen corporal, basada en la experiencia corporal, y el cuerpo erótico como un aspecto de la relación con el cuerpo como objeto interno. Propone entonces la siguiente hipótesis: si bien la imagen corporal y la representación de la relación afectiva de la madre con el cuerpo del niño, en sus aspectos positivos y negativos, contribuyen ambos a la formación del yo corporal, solo la imagen corporal que puede compartirse con la madre de manera satisfactoria para ambos, puede ser introyectada por el yo y constituir el objeto interno erótico amado (AU)

The autor seeks to draw distinction between body image, based on the experience of the body, and the erotic body as an aspect of the relationship with the body as an internal object. She then puts forward the following hypothesis: while body image and the representation of the mother´s affective relationship with the infant´s body, in its positive and negative aspects, both contribute to the formation of the body ego, only the body image able to be shared with the mother in an acceptable way for both may be introjected by the ego and constitute the erotic loved internal object (AU)

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.

[Treatment of extreme tumour pain with morphine and s-ketamine A case report of an 11-year old girl]. / Therapie extremer Tumorschmerzen mit Morphin und (S)-Ketamin. Falldarstellung eines 11-jährigen Mädchens.

We are reporting on the case of an 11-year old girl with a malignant tumour. The extreme pain throughout the body could not be treated by conventional methods. By intravenous application of a morphine and s-ketamine mixture we were able to achieve a very effective analgesic result. Apart from the opiate effect of the morphine the decisive factor was the NMDA-antagonism of the s-ketamine. The latter suppresses central sensitisation and chronic pain and reduces or even prevents the development of opioid tolerance. It was possible to use smaller opiate doses more effectively, thus reducing the side effects of the pain therapy. Under associated whole-body thermochemotherapy the girl experienced general pain relief and we were able to return to conventional therapy with a fentanyl plaster.

Gross-total surgery of supratentorial low-grade gliomas under intraoperative MR guidance.

BACKGROUND AND PURPOSE: Length of survival of patients with low-grade glioma correlates with the extent of tumor resection. These tumors, however, are difficult to distinguish intraoperatively from normal brain tissue, often leading to incomplete resection. Our goal was to evaluate the effectiveness of intraoperative MR guidance in achieving gross-total resection. METHODS: We studied 12 patients with low-grade glioma who underwent surgery within a vertically open 0.5-T MR system. During surgery, localization of residual tumor tissue was guided by interactive, near real-time imaging. The amount of residual tumor tissue on MR images was evaluated at the point of the operation at which the neurosurgeon would have terminated the procedure under conventional conditions (first control) and again before closing the craniotomy. RESULTS: Significant residual tumor (more than 10% of original tumor volume) was shown in eight patients at the first control condition. The percentage of resection varied from 26% to 100% (mean, 68%) at this time. Twelve tissue samples from seven patients were obtained in areas identified as residual tumor on MR images. In 10 cases, the neuropathologic investigation confirmed the presence of residual low-grade glioma; in two cases, the borderzone of tumor was identified. In evaluating the final sets of images, we found total resection in six cases, over 90% resection in five cases, and 85% resection in one case (mean, 96%). CONCLUSION: Surgical treatment of low-grade gliomas under intraoperative MR guidance provides improved resection results with maximal patient safety.

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.

Transurethral resection and partial cystectomy for invasive bladder cancer.

Bladder-preserving modalities for patients with invasive bladder cancer have become increasingly popular in recent years. Surgical-only approaches, such as transurethral resection (TUR) or partial cystectomy, are unique among a variety of bladder-preserving modalities, most of which involve combination with radiation and chemotherapy. TUR and partial cystectomy remain incompletely evaluated due to relatively small series in the literature and the lack of standardized selection criteria. The outcome as measured by long-term bladder preservation and overall survival is not dissimilar to concurrent radical cystectomy series, possibly because of positive selection of patients.

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.

Complete androgen blockade for prostate cancer: what went wrong?

PURPOSE: We summarized and critically assessed all available data from phase III clinical trials on complete androgen blockade versus surgical or medical castration alone. MATERIALS AND METHODS: Published results in journals and abstracts of phase III trials, and published meta-analyses were reviewed. We also reviewed quality of life and toxicity issues associated with the addition of antiandrogens to medical or surgical castration. Finally, we discuss the original rationale for complete androgen blockade in the context of current knowledge. RESULTS: A total of 27 clinical trials using various combinations of androgen deprivation were identified, of which 3 showed a statistically significant benefit for the complete androgen blockade arm. There were 5 publications of meta-analyses that each used different selection criteria for the inclusion of studies in the final analysis. Toxicity and quality of life have not been widely investigated in prospective fashion but the available data suggest a higher toxicity rate and decreased quality of life with complete androgen blockade. CONCLUSIONS: The extensive body of data does not support routine use of antiandrogens in combination with medical or surgical castration as first line hormonal therapy in patients with metastatic prostate cancer.

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.