Endocrine symptom assessment in women with breast cancer: what a simple "yes" means

GOALS OF WORK: To investigate the self-reported symptoms related to endocrine therapy in women with early or advanced breast cancer and the impact of these symptoms on quality of life (QL) indicators. MATERIALS AND METHODS: Symptom occurrence was assessed by the Checklist for Patients on Endocrine Therapy (C-PET) and symptom intensity was assessed by linear analogue self-assessment (LASA) indicators. Patients also responded to global LASA indicators for physical well-being, mood, coping effort and treatment burden. Associations between symptoms and these indicators were analysed by linear regression models. MAIN RESULTS: Among 373 women, the distribution of symptom intensity showed considerable variation in patients reporting a symptom as present. Even though patients recorded a symptom as absent, some patients reported having experienced that symptom when responding to symptom intensity, as seen for decreased sex drive, tiredness and vaginal dryness. Six of 13 symptoms and lower age had a detrimental impact on the global indicators, particularly tiredness and irritability. CONCLUSIONS: Patients' experience of endocrine symptoms needs to be considered both in patient care and research, when interpreting the association between symptoms and QL.

[Infections in pregnancy]

Infections in pregnancy may complicate its course and harm the fetus or newborn after vertical transmission. Treatment of asymptomatic bacteriuria is mandatory in pregnant women given the high risk of secondary pyelonephritis. Intraamniotic infection usually arises by the ascending route and is associated with premature rupture of membranes. Vaginal infections promote preterm labour or premature rupture of membranes and may be transmitted to the child during labour. They must therefore be treated although they often cause little discomfort to the pregnant woman. Systemic infections due to viral, protozoal and bacterial pathogens may be transmitted transplacentally and cause embryopathies, fetopathies or neonatal infections. Depending on the responsible agent the negative impact on the course of pregnancy and on the fetus' or neonate's health can be prevented or reduced by prophylactic or therapeutic interventions.

Ear acupuncture points in neonates

OBJECTIVE: The aim of this study was to determine the presence and absence of acupuncture ear points in healthy neonates. DESIGN: This was a prospective observational study performed at a university teaching hospital. Subjects: The subjects were healthy neonates. We compared male and female neonates, right and left lobe, term and preterm deliveries, and cesarean sections versus vaginal deliveries. Examinations took place on the fifth day after delivery and were performed by a neuronal pen (SVESA 1070, SVESA GmbH, Munich, Germany). An integrated optical signal detected the ear points that were assigned to the Chinese ear map. MAIN OUTCOME MEASURES: This study looked at the presence and absence of acupuncture ear points in neonates. RESULTS: There were 27 male neonates and 23 female neonates. In 66% of neonates, no points at all were found. We detected 0-4 points on the right lobe and 0-2 points on the left lobe. The psychovegetative rim was the most common point in 26% of all children. No psychic points were detected. No significant differences were found between right and left ear lobes, male and female neonates, or term and preterm deliveries with respect to numbers of points or access of points. Moreover, there were no differences among modes of delivery. CONCLUSIONS: Some ear points in healthy neonates are detectable and not dependent on side of the ear lobe. Females had significantly more acupuncture points. There was an extremely significant difference in the group with 2 active earpoints between cesarean and vaginally delivered neonates. The most important point was the psychovegetative rim and the absence of psychic points in favor of the organ points. Possibly, ear points in neonates could be used for diagnostic and therapeutic options in neonates in the future.

Outcome of treated anogenital intraepithelial neoplasia among human immunodeficiency virus-infected women

OBJECTIVE: To determine characteristics and clinical course of high-grade anogenital intraepithelial neoplasia (AIN) in human immunodeficiency virus (HIV)-infected women. STUDY DESIGN: HIV-positive women with biopsy-proven high-grade (II and III) vulvar (VIN), vaginal (VAIN) or perianal intraepithelial neoplasia (PAIN) were identified in the electronic databases of 2 colposcopy clinics. RESULTS: A total of 31 patients were identified from 1992 to 2007, of which 30 had a mean follow-up of 47.7 months (SD = 46.0; range, 2.6-166.2). Of the patients, 77.4% had VIN, 12.9% VAIN and 9.7% PAIN at first diagnosis. Age at diagnosis of IN was 36.2 years (SD +/- 5.2; range, 23.5-47.0). Ninety percent of patients received antiretroviral therapy at first diagnosis of IN; 65% (13 of 20) of patients with a follow-up of > 2 years required a second treatment, and 2 developed invasive vulvar cancer (10%). CONCLUSION: AIN among HIV-positive women shows a high relapse rate despite treatment modality used and a substantial invasive potential.

[Follow-up after malignant tumours of the uterus (cancer of the uterine corpus / cervical cancer)]

Malignant uterine tumours can affect the corpus or the cervix. The endometrial carcinoma with its different histological subtypes counts for most of the malignomas of the uterine body. But the rare category of uterine sarcomas (carcinosarcomas, leiomyosarcomas as well as endometrial stromal sarcomas) also belongs to this group. Cervical cancer presents an own entitity, regarding both histology and therapeutic options. Endometrial cancer is the most common genital malignoma in Northern Europe and North America. Histologically, the endometrial cancer can be subdivided in two groups: type I is hormonal sensitive and well differentiated, type II represents an undifferenciated aggressive tumour with poor prognosis. In general, the patient is elderly. Due to the main symptom - abnormal vaginal bleeding - endometrial cancer is detected in an early stage in about 75% of all patients. First choice in therapy is stage related surgery. Follow-up schemes have not proved yet to improve survival, therefore clear guidelines are missing. National and international groups recommend regular follow-up visits to detect the early vaginal vault relapse which is curable. Cervical cancer is mainly a squamous cell carcinoma and oncogenic Human Papilloma Virus (HPV) associated. Surgery is only indicated up to stage IIA, advanced stages should be treated by radio-chemotherapy. Several studies have shown that follow-up visits can improve survival rates. Intention is the detection of the curable local relapse.

Correction of erosion after suburethral sling insertion for stress incontinence: results and related sexual function

BACKGROUND: Suburethral slings are commonly used for the surgical treatment of female stress incontinence; occasionally they can cause erosion and dyspareunia. OBJECTIVES: The primary aim of this study is to determine the outcome after reclosure of the vaginal epithelium for suburethral sling erosion. Sexual function was assessed before and after intervention using the Female Sexual Function Index (FSFI) questionnaire. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective case-controlled study in which, between December 2005 and December 2007, we included patients who were referred to the Department of Urogynaecology because of vaginal erosion after suburethral sling insertion for urinary stress incontinence. For evaluation of sexual function, all patients filled in an FSFI questionnaire before intervention and at follow-up. All patients underwent gynaecological examination including colposcopy, and the site and size of the defect were noted. INTERVENTION: The edge of the vaginal epithelium was trimmed, mobilized, and closed with interrupted vertical Vicryl mattress sutures in a single layer. MEASUREMENTS: FSFI questionnaire and clinical findings. RESULTS AND LIMITATIONS: Twenty-one patients were included in the study. Eighteen patients with larger defects were operated on, and three defects healed after topical application of estrogen cream. In 16 patients, the defect had healed at follow-up; two patients with persisting defects were brought back to surgery and the procedure was repeated, paying particular attention to tension-free adaptation of vaginal tissue. In one patient, partial sling removal was performed after the second failed intervention. The domains of desire (p<0.0001), arousal (p<0.0003), lubrication (p<0.0001), satisfaction (p<0.0130), and pain (p<0.0001) improved significantly. Orgasm remained unchanged (p=0.4130; all two-tailed t-test). CONCLUSION: Suburethral erosion can be treated effectively by resuturing. Sexual function is improved in regard to desire, arousal, lubrication, satisfaction, and pain, but not orgasm. In septic patients and patients with a history of radiation, grossly infected tissue, or severe pain, excision of the mesh needs to be considered.

Sexual and organ function in patients with symptomatic prolapse: are pessaries helpful?

OBJECTIVE: To evaluate quality of life and pelvic organ and sexual function before and during pessary use in patients with symptomatic pelvic organ prolapse and to determine reasons which lead to cessation of pessary use. DESIGN: Prospective observational study. SETTING: Tertiary referral center. PATIENT(S): Patients with symptomatic stage II or more prolapse of the anterior, posterior, or apical vaginal wall with or without uterus were included in this study. INTERVENTION(S): We used the Female Sexual Function Index questionnaire and the Sheffield prolapse questionnaire. For quality of life we used the King's Health Questionnaire. MAIN OUTCOME MEASURE(S): Main outcome measures were quality of life and sexual and pelvic organ function. RESULT(S): A total of 73 women participated in this study; 31 were sexually active. Desire, lubrication, and sexual satisfaction showed statistically significant improvement, and orgasm remained unchanged. Statistically significant improvement in the feeling of bulge occurred during therapy, stool outlet problems were significantly improved, overactive bladder symptoms were significantly better, and pessaries did not significantly alter incontinence. CONCLUSION(S): Pessaries have been shown to be a viable noninvasive treatment for pelvic organ prolapse improving organ and sexual function as well as general wellbeing.

Sexual function after suburethral sling removal for dyspareunia

INTRODUCTION: Impact on sexual function has received little attention in the medical literature for a long time. Because of the site of insertion of permanent tension free vaginal tape (TVT) the G spot might be affected or the tape might interfere with arousal and sensory stimulation. Recent studies have reported varying degrees of sexual impairment after TVT insertion ranging from 0% to 15% including dyspareunia. AIM: The aim of this study was to evaluate sexual function before and after suburethral sling removal due to postoperative female de novo dyspareunia. As a secondary outcome, general patients' satisfaction with their overall continence situation was assessed. PATIENTS AND METHODS: Between December 2005 and December 2007, we included 18 female patients who complained of de novo dyspareunia after suburethral sling insertion for urinary stress incontinence. All patients filled in an FSFI questionnaire prior to sling removal and at 3 months postoperatively. Additionally, all women were asked to estimate their general satisfaction regarding their continence situation using a Visual Analogue Scale (VAS) from 0 to 10, with 0 being the least satisfying situation and 10 being the most satisfying situation. All patients underwent gynaecological examination including ICS-pelvic organ prolapse staging (ICS-POP score). RESULTS: Of the 18 slings, ten were transobturator tapes (6 x TVT-O, 2 x Monarch, 2 x unknown) and eight were retropubic tapes (7 x TVT, 1 x SPARC). Desire, arousal, lubrication, satisfaction, and pain improved statistically significant. Orgasm scores were low with median scoring of 1.5 scores before and 1.0 scores after sling removal, and they did not change significantly after sling removal. The satisfaction rate deteriorated from a median of 7 (95% confidence interval [CI] 6.3-7.7) to a median of 4 (95% CI 3.7-5.1; p=0.99) but not statistically significant. CONCLUSIONS: Sexual function in patients with de novo dyspareunia is likely to improve after sling removal but not in all domains. Bladder function may deteriorate.

A diagnostically challenging case of ureterovaginal fistula after laparoscopic hysterectomy

A complicated case of iatrogenic ureterovaginal fistula in a 56-year-old woman after laparoscopic-assisted vaginal hysterectomy, which persisted after several attempts of repair including ureterocystoneostomy, is presented. Accurate radiologic work-up enabled us to identify a refluxing ureteral stump, which was not ligated at the time of ureterocystoneostomy, as the origin of urinary leakage. Surgical principles that should be adhered to when managing such complex cases to obtain successful long-lasting outcome are described.

Ultrasound of the pediatric female pelvis

Pelvic pain is a common indication for ultrasound examinations in female pediatric patients. Many pathological processes affect the female pelvis in childhood. Knowledge of the normal ultrasound appearance of the pelvic organs is the basis for the recognition of pathologic findings. Pelvic pain in children is a nonspecific clinical finding often prompting use of ultrasound. Other indications for pelvic ultrasound in female children include workup of cysts seen on fetal ultrasound, urogenital malformations in newborns, precocious puberty, vaginal discharge or abnormal bleeding, and amenorrhea. Knowledge of differential diagnosis for disease processes of the female pelvic organs is essential. Ultrasound is the imaging modality of choice for evaluating the pediatric female pelvis.

Proliferation and apoptosis in mammary epithelium during the rat oestrous cycle

AIM: During each oestrous cycle, the mammary gland is subject to changes in ovarian hormone levels. It responds with limited proliferation, differentiation and regression. To understand the processes resulting in these changes, particularly the regulation of cell death, we examined protein levels in mammary epithelium during the oestrous cycle of the Sprague-Dawley rat. METHODS: Studies of serum hormone levels, vaginal smears, uterine weight and morphology, mammary gland morphology, proliferation and apoptotic indices, and protein levels during the stages of the Sprague-Dawley rat oestrous cycle were used to examine the response of mammary epithelium to the oestrous cycle. RESULTS: Proliferation of mammary epithelium was greater in diestrus and proestrus, while apoptosis was increased in metestrus and diestrus. Growth factor-, hormone- and anchorage-mediated cell survival signalling, indicated by activation of Stat5A, FAK and Akt 1 and expression of anti-apoptotic Bcl-2 family members, was greater in proestrus and reduced in metestrus. In contrast, the levels of pro-apoptotic Bcl-2 family members and proteins associated with apoptosis in mammary epithelium (TGFbeta3, pStat3) were increased during metestrus and diestrus. CONCLUSION: Decreases in growth factor, hormone and cell attachment survival signals corresponded with increased apoptosis during the second half of the oestrous cycle. The protein levels detected during oestrus suggest parallels to apoptosis in mammary involution.

Sexual transmission of HIV according to viral load and antiretroviral therapy: systematic review and meta-analysis

OBJECTIVES: To synthesize the evidence on the risk of HIV transmission through unprotected sexual intercourse according to viral load and treatment with combination antiretroviral therapy (ART). DESIGN: Systematic review and meta-analysis. METHODS: We searched Medline, Embase and conference abstracts from 1996-2009. We included longitudinal studies of serodiscordant couples reporting on HIV transmission according to plasma viral load or use of ART and used random-effects Poisson regression models to obtain summary transmission rates [with 95% confidence intervals, (CI)]. If there were no transmission events we estimated an upper 97.5% confidence limit. RESULTS: We identified 11 cohorts reporting on 5021 heterosexual couples and 461 HIV-transmission events. The rate of transmission overall from ART-treated patients was 0.46 (95% CI 0.19-1.09) per 100 person-years, based on five events. The transmission rate from a seropositive partner with viral load below 400 copies/ml on ART, based on two studies, was zero with an upper 97.5% confidence limit of 1.27 per 100 person-years, and 0.16 (95% CI 0.02-1.13) per 100 person-years if not on ART, based on five studies and one event. There were insufficient data to calculate rates according to the presence or absence of sexually transmitted infections, condom use, or vaginal or anal intercourse. CONCLUSION: Studies of heterosexual discordant couples observed no transmission in patients treated with ART and with viral load below 400 copies/ml, but data were compatible with one transmission per 79 person-years. Further studies are needed to better define the risk of HIV transmission from patients on ART.

Effects of female genital mutilation on birth outcomes in Switzerland

OBJECTIVE: The primary aim of this study was to determine the desires and wishes of pregnant patients vis-à-vis their external genital anatomy after female genital mutilation (FGM) in the context of antenatal care and delivery in a teaching hospital setting in Switzerland. Our secondary aim was to determine whether women with FGM and non-mutilated women have different fetal and maternal outcomes. DESIGN: A retrospective case-control study. SETTING: A teaching hospital. POPULATION: One hundred and twenty-two patients after FGM who gave consent to participate in this study and who delivered in the Department of Obstetrics and Gynaecology in the University Hospital of Berne and 110 controls. METHODS: Data for patients' wishes concerning their FGM management, their satisfaction with the postpartum outcome and intrapartum and postpartum maternal and fetal data. As a control group, we used a group of pregnant women without FGM who delivered at the same time and who were matched for maternal age. MAIN OUTCOME MEASURES: Patients' satisfaction after delivery and defibulation after FGM, maternal and fetal delivery data and postpartum outcome measures. RESULTS: Six percent of patients wished to have their FGM defibulated antenatally, 43% requested a defibulation during labour, 34% desired a defibulation during labour only if considered necessary by the medical staff and 17% were unable to express their expectations. There were no differences for FGM patients and controls regarding fetal outcome, maternal blood loss or duration of delivery. FGM patients had significantly more often an emergency Caesarean section and third-degree vaginal tears, and significantly less first-degree and second-degree tears. CONCLUSION: An interdisciplinary approach may support optimal antenatal and intrapartum management and also the prevention of FGM in newborn daughters.

Prevention of postmenopausal bone loss using tibolone or conventional peroral or transdermal hormone replacement therapy with 17beta-estradiol and dydrogesterone

Postmenopausal bone loss can be prevented by continuous or intermittent estradiol (E2) administration. Concomitant progestogen therapy is mandatory in nonhysterectomized women to curtail the risk of endometrial hyperplasia or cancer. However, the recurrence of vaginal bleeding induced by sequential progestogen therapy in addition to continuous estrogen administration is one of the reasons for noncompliance to hormone replacement therapy (HRT). Tibolone, a synthetic steroid with simultaneous weak estrogenic, androgenic, and progestational activity, which does not stimulate endometrial proliferation, has recently been proposed for the treatment of climacteric symptoms. To compare the efficacy of conventional oral and transdermal HRT with that of tibolone in the prevention of postmenopausal bone loss, 140 postmenopausal women (age, 52 +/- 0.6 years; median duration of menopause, 3 years) were enrolled in an open 2-year study. Volunteers had been offered a choice between HRT and no therapy (control group, CO). Patients selecting HRT were randomly allocated to one of the following three treatment groups: TIB, tibolone, 2.5 mg/day continuously, orally; PO, peroral E2, 2 mg/day continuously, plus sequential oral dydrogesterone (DYD), 10 mg/day, for 14 days of a 28-day cycle; TTS, transdermal E2 by patch releasing 50 microg/day, plus DYD as above. Bone densitometry of the lumbar spine, upper femur, and whole body was performed using dual-energy X-ray absorptiometry at baseline, and then 6, 12, 18, and 24 months after initiation of therapy. One hundred and fifteen women (82%) completed the 2 years of the study. The dropout rate was similar in each group. Over 2 years, bone preservation was observed in all three treatment groups as compared with controls, without significant differences among treatment regimens. In conclusion, tibolone can be regarded as an alternative to conventional HRT to prevent postmenopausal bone loss.

Exemestane Versus Anastrozole in Postmenopausal Women With Early Breast Cancer: NCIC CTG MA.27—A Randomized Controlled Phase III Trial

PURPOSE In patients with hormone-dependent postmenopausal breast cancer, standard adjuvant therapy involves 5 years of the nonsteroidal aromatase inhibitors anastrozole and letrozole. The steroidal inhibitor exemestane is partially non-cross-resistant with nonsteroidal aromatase inhibitors and is a mild androgen and could prove superior to anastrozole regarding efficacy and toxicity, specifically with less bone loss. PATIENTS AND METHODS We designed an open-label, randomized, phase III trial of 5 years of exemestane versus anastrozole with a two-sided test of superiority to detect a 2.4% improvement with exemestane in 5-year event-free survival (EFS). Secondary objectives included assessment of overall survival, distant disease-free survival, incidence of contralateral new primary breast cancer, and safety. RESULTS In the study, 7,576 women (median age, 64.1 years) were enrolled. At median follow-up of 4.1 years, 4-year EFS was 91% for exemestane and 91.2% for anastrozole (stratified hazard ratio, 1.02; 95% CI, 0.87 to 1.18; P = .85). Overall, distant disease-free survival and disease-specific survival were also similar. In all, 31.6% of patients discontinued treatment as a result of adverse effects, concomitant disease, or study refusal. Osteoporosis/osteopenia, hypertriglyceridemia, vaginal bleeding, and hypercholesterolemia were less frequent on exemestane, whereas mild liver function abnormalities and rare episodes of atrial fibrillation were less frequent on anastrozole. Vasomotor and musculoskeletal symptoms were similar between arms. CONCLUSION This first comparison of steroidal and nonsteroidal classes of aromatase inhibitors showed neither to be superior in terms of breast cancer outcomes as 5-year initial adjuvant therapy for postmenopausal breast cancer by two-way test. Less toxicity on bone is compatible with one hypothesis behind MA.27 but requires confirmation. Exemestane should be considered another option as up-front adjuvant therapy for postmenopausal hormone receptor-positive breast cancer.