Efficacy of topical progesterone versus topical clobetasol propionate in patients with vulvar Lichen sclerosus - A double-blind randomized phase II pilot study.

BACKGROUND Lichen sclerosus (LS) is a chronic inflammatory skin disease that mostly affects the anogenital region of women and lowers patients' quality of life. Current standard treatment of LS is topical steroids. OBJECTIVE To evaluate the efficacy of topical progesterone 8% ointment and compare to standard therapy with topical clobetasol propionate 0.05% in premenopausal women presenting with previously untreated early onset LS. STUDY DESIGN Randomized, double-blind, 2-arm, single center superiority trial in premenopausal women with histologically confirmed vulvar LS who were randomized in a 1:1 ratio to receive clobetasol propionate 0.05% ointment or progesterone 8% ointment. The primary outcome was the clinical severity LS score after 12 weeks, which consists of six clinical features assessed by the physician. Secondary outcomes were the symptom severity LS score, which consists of three symptoms rated by the patient, the Short Form SF-12 physical and mental health scores, and adverse events. Response to medication was assessed by biopsy at the end of the treatment to evaluate inflammatory parameters. RESULTS Overall, 105 women were screened, 102 underwent vulvar biopsy and 37 received a histologically confirmed diagnosis of LS and were randomized: 17 to progesterone and 20 to clobetasol propionate. At 12 weeks, the mean clinical LS scores improved from 4.6 (SD 2.0) to 4.5 (SD 1.7) in the progesterone arm, and from 4.6 (SD 2.8) to 2.9 (SD 2.2) in the clobetasol propionate arm (difference in favor of clobetasol 1.61; 95% CI 0.44 to 2.77, p = 0.009), and the mean symptom severity LS scores improved from 4.5 (SD 3.8) to 3.1 (SD 3.0) in the progesterone arm, and from 4.7 (SD 2.8) to 1.9 (SD 1.8) in the clobetasol propionate arm (difference in favor of clobetasol 1.32; 95% CI -0.25 to 2.89, p = 0.095). LS was in complete remission in 6 out of 10 patients (60%) with available biopsy in the progesterone arm, and in 13 out of 16 patients (81.3%) in the clobetasol propionate arm (odds ratio in favor of clobetasol 0.35; 95% CI 0.06 to 2.06, p = 0.234). No drug-related serious adverse event occurred during the trial. CONCLUSIONS Topical progesterone 8% ointment is inferior to standard therapy with topical clobetasol propionate 0.05% in previously untreated premenopausal women with vulvar LS after 12 weeks treatment

Acellular Dermal Matrix (Permacol®) for Heterologous Immediate Breast Reconstruction after Skin-Sparing Mastectomy in Patients with Breast Cancer: A Single-Institution Experience and a Review of the Literature.

OBJECTIVE Skin-sparing mastectomy (SSM) with immediate heterologous reconstruction is a safe oncological option in surgical therapy of early breast cancer. Permacol® is an acellular dermal matrix (ADM) placed between the implant and the skin to improve lower pole projection and implant coverage. The aim of our study was to evaluate the outcome with a focus on patient satisfaction after 6 months and to analyze physical changes of ADM. METHODS 10 patients who underwent SSM with Permacol® were analyzed retrospectively. All patients were followed using a satisfaction questionnaire and an ultrasound evaluation of the tissue thickness of the pectoralis muscle and the Permacol®. RESULTS No intraoperative complications were observed. One patient required removal of the implant for necrosis after 3 months. Half of the patients underwent secondary corrective surgery. A statistically significant thinning of the pectoralis muscle was observed, compared to the thickening of the Permacol®. A majority of the patients were satisfied with the operation, and we found a correlation between lower body mass index and patient satisfaction. CONCLUSION In our small case series Permacol®-assisted immediate reconstruction is shown to be an option for selected cases. Physical changes of Permacol® result in a symmetrical coverage of the implant, which may improve cosmetic outcome

Predictive factors for preterm delivery under rural conditions in post-tsunami Banda Aceh

Objective: To assess the risk for preterm deliveries <37 week of gestation and associated prevalence of vaginal infection in a rural setting after the tsunami in Banda Aceh, Indonesia. Methods: Wet mount microscopy, vaginal pH and vaginal swabs for microbiological culture were collected in pregnant women during the 2nd trimester from February to June of 2005 in four temporary outpatient clinics and the patients were followed up until delivery. Results: One hundred and fifty-nine pregnant patients were screened. Sixty-two could be followed up until delivery. Thirty-nine (62.9%) delivered at term and 23 (37.1%) delivered prematurely. Significant risk factors for preterm delivery were a history of preterm delivery and group B streptococcus infection. Increased vaginal pH alone had no significant influence on preterm delivery, although there was a trend. Conclusion: The rate of preterm delivery was high in this cohort. We suggest risk stratification for preterm delivery in rural conditions by performing a vaginal pH and wet mount microscopy. If either is suspect we suggest collecting a vaginal swab for microbiological culture for targeted treatment. Patients with a history of preterm delivery are at increased risk and should be monitored closely

Oncoplastic Breast Consortium consensus conference on nipple-sparing mastectomy

Purpose Indications for nipple-sparing mastectomy (NSM) have broadened to include the risk reducing setting and locally advanced tumors, which resulted in a dramatic increase in the use of NSM. The Oncoplastic Breast Consortium consensus conference on NSM and immediate reconstruction was held to address a variety of questions in clinical practice and research based on published evidence and expert panel opinion. Methods The panel consisted of 44 breast surgeons from 14 countries across four continents with a background in gynecology, general or reconstructive surgery and a practice dedicated to breast cancer, as well as a patient advocate. Panelists presented evidence summaries relating to each topic for debate during the in-person consensus conference. The iterative process in question development, voting, and wording of the recommendations followed the modified Delphi methodology. Results Consensus recommendations were reached in 35, majority recommendations in 24, and no recommendations in the remaining 12 questions. The panel acknowledged the need for standardization of various aspects of NSM and immediate reconstruction. It endorsed several oncological contraindications to the preservation of the skin and nipple. Furthermore, it recommended inclusion of patients in prospective registries and routine assessment of patient-reported outcomes. Considerable heterogeneity in breast reconstruction practice became obvious during the conference. Conclusions In case of conflicting or missing evidence to guide treatment, the consensus conference revealed substantial disagreement in expert panel opinion, which, among others, supports the need for a randomized trial to evaluate the safest and most efficacious reconstruction techniques

Oncoplastic Breast Consortium consensus conference on nipple-sparing mastectomy.

Purpose Indications for nipple-sparing mastectomy (NSM) have broadened to include the risk reducing setting and locally advanced tumors, which resulted in a dramatic increase in the use of NSM. The Oncoplastic Breast Consortium consensus conference on NSM and immediate reconstruction was held to address a variety of questions in clinical practice and research based on published evidence and expert panel opinion. Methods The panel consisted of 44 breast surgeons from 14 countries across four continents with a background in gynecology, general or reconstructive surgery and a practice dedicated to breast cancer, as well as a patient advocate. Panelists presented evidence summaries relating to each topic for debate during the in-person consensus conference. The iterative process in question development, voting, and wording of the recommendations followed the modified Delphi methodology. Results Consensus recommendations were reached in 35, majority recommendations in 24, and no recommendations in the remaining 12 questions. The panel acknowledged the need for standardization of various aspects of NSM and immediate reconstruction. It endorsed several oncological contraindications to the preservation of the skin and nipple. Furthermore, it recommended inclusion of patients in prospective registries and routine assessment of patient-reported outcomes. Considerable heterogeneity in breast reconstruction practice became obvious during the conference. Conclusions In case of conflicting or missing evidence to guide treatment, the consensus conference revealed substantial disagreement in expert panel opinion, which, among others, supports the need for a randomized trial to evaluate the safest and most efficacious reconstruction techniques

[Sarcomas and mixed mesodermal tumors of the uterus]

Malignant mesodermal tumors of the uterus are an inhomogenous group of uterine malignancies with different pathogenesis, clinical presentation and prognosis. These rare tumors represent approximately 1 % of all uterine malignancies. The aggressive carcinosarcomas or mixed muellerian tumors are defined by mixed malignant epithelial and malignant mesodermal histopathology and are of the same precursor cell origin like endometrial cancer. Thus, carcinosarcomas were reclassified by the FIGO as an aggressive type of endometrial cancer and treated like type II endometrial cancer. Adenosarcomas are also mixed tumors with benign epithelial proliferation and malignant mesodermal cell growth, have a good prognosis and represent less than 5 % of all mesodermal uterine malignancies. Besides carcinosarcomas, the pure mesodermal leiomyosarcomas are the most common mesodermal malignancies. Patients with leiomyosarcamos are usually perimenopausal, and although more than half of the patients present with symptoms, diagnosis occurs incidentally in most cases in final histopathologic workup of an excised putative myoma or uterus. Adequate anamnesis, gynecologic examination and careful imaging by transvaginal ultrasound in the preoperative setting might hint to correct differential diagnosis in many cases. Overall the prognosis of uterine leiomyomas is poor. Malignancies of the endometrial stroma are very rare and divided in two subgroups, the mostly estrogen receptor positive endometrial stromal sarcoma, which occur preferably in premenopausal women and show a favorable prognosis, and the very aggressive undifferentiated endometrial sarcomas. The more rare undifferentiated endometrial sarcomas occur in postmenopausal women and most patients die in the first two years after diagnosis. Risk stratification of preoperative differential diagnosis requires improvements and the correct histopathologic workup of mesodermal uterine malignancies is still a challenge for pathologists

Gonadotropin-releasing hormone type II antagonist induces apoptosis in MCF-7 and triple-negative MDA-MB-231 human breast cancer cells in vitro and in vivo

Triple-negative breast cancer does not express estrogen and progesterone receptors, and no overexpression/amplification of the HER2-neu gene occurs. Therefore, this subtype of breast cancer lacks the benefits of specific therapies that target these receptors. Today chemotherapy is the only systematic therapy for patients with triple-negative breast cancer. About 50% to 64% of human breast cancers express receptors for gonadotropin-releasing hormone (GnRH), which might be used as a target. New targeted therapies are warranted. Recently, we showed that antagonists of gonadotropin-releasing hormone type II (GnRH-II) induce apoptosis in human endometrial and ovarian cancer cells in vitro and in vivo. This was mediated through activation of stress-induced mitogen-activated protein kinases (MAPKs) p38 and c-Jun N-terminal kinase (JNK), followed by activation of proapoptotic protein Bax, loss of mitochondrial membrane potential, and activation of caspase-3. In the present study, we analyzed whether GnRH-II antagonists induce apoptosis in MCF-7 and triple-negative MDA-MB-231 human breast cancer cells that express GnRH receptors. In addition, we ascertained whether knockdown of GnRH-I receptor expression affects GnRH-II antagonist-induced apoptosis and apoptotic signaling

Safe vaginal uterine morcellation following total laparoscopic hysterectomy.

The minimally invasive approach for hysterectomy with proven benefits and lower morbidity has become the gold standard, even in women with large uterine masses. Most women with a malignant condition present with abnormal vaginal bleeding and/or suspicious imaging such that few are diagnosed by final histopathology after surgery. However, if a malignancy is not diagnosed preoperatively, intraabdominal morcellation for uterus extraction has an increased risk for potential tumor spread and peritoneal metastases, especially in cases of unexpected leiomyosarcoma. We describe a simple method to wrap the uterus in a contained environment with a plastic bag through the posterior vaginal fornix prior to conventional coring morcellation for vaginal extraction in total laparoscopic hysterectomy. We further describe our experience with a risk stratification and treatment algorithm to implement this procedure in daily routine. A video and an illustrating sketch demonstrate the simplicity and safety of the procedure

Should Groin Recurrence Still Be Considered as a Palliative Situation in Vulvar Cancer Patients?: A Brief Report.

OBJECTIVE To assess survival after groin recurrence in patients with vulvar cancer in the transition period of the implementation of the sentinel lymph node biopsy procedure. Recurrence of groin metastases in vulvar cancer patients is assumed to be lethal. It is unknown if early detection of relapse and multimodal treatment strategies improve the outcome of patients with groin recurrence. METHODS Multicenter retrospective cohort study of patients with recurrent vulvar cancer who presented with groin and/or pelvic lymph node metastases between 2000 and 2014 at 3 tertiary referral hospitals. Our primary outcome was to assess survival after groin recurrence of vulvar cancer and the influence of multimodal treatment. All analyses were done using Stata 12 (Stata Corporation, College Station, Tex). Hazard ratios (HRs) and their corresponding 95% confidence intervals were calculated using a Cox proportional hazards model. RESULTS We identified 30 patients with a median time from diagnosis to groin recurrence of 10 months. The median follow-up of patients who were alive at the time of analysis was 22 months (range, 9-123 months). A Kaplan-Meier estimate showed an overall survival rate of 50% after 7 years. Patients with multimodal groin relapse treatment performed better than those with single-mode treatment (HR, 0.25; P = 0.037). Lymph node metastases at diagnosis were also associated with lower survival (HR, 6.11; P = 0.020). We observed a trend toward lower survival with a tumor size greater than T1 (HR, 2.55; P = 0.111). The time from diagnosis to groin recurrence had no influence on survival (HR, 0.99; P = 0.561). CONCLUSIONS Close follow-up visits for at least 2 years are important to detect recurrent disease in groin and pelvic lymph nodes. Treatment of recurrent groin metastases should no longer be considered as a palliative situation--given that one half of the patients will have long-term survival after multimodal treatment strategies