Nab-paclitaxel weekly versus dose-dense solvent-based paclitaxel followed by dose-dense epirubicin plus cyclophosphamide in high-risk HR+/HER2- early breast cancer: results from the neoadjuvant part of the WSG-ADAPT-HR+/HER2- trial.

BACKGROUND: In high-risk hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC), nanoparticle albumin-bound (nab)-paclitaxel showed promising efficacy versus solvent-based (sb)-paclitaxel in neoadjuvant trials; however, optimal patient and therapy selection remains a topic of ongoing research. Here, we investigate the potential of Oncotype DX® recurrence score (RS) and endocrine therapy (ET) response (low post-endocrine Ki67) for therapy selection. PATIENTS AND METHODS: Within the WSG-ADAPT trial (NCT01779206), high-risk HR+/HER2- EBC patients were randomized to (neo)adjuvant 4× sb-paclitaxel 175 mg/m2 q2w or 8× nab-paclitaxel 125 mg/m2 q1w, followed by 4× epirubicin + cyclophosphamide (90 mg + 600 mg) q2w; inclusion criteria: (i) cN0-1, RS 12-25, and post-ET Ki67 >10%; (ii) cN0-1 with RS >25. Patients with cN2-3 or (G3, baseline Ki67 ≥40%, and tumor size >1 cm) were allowed to be included without RS and/or ET response testing. Associations of key factors with pathological complete response (pCR) (primary) and survival (secondary) endpoints were analyzed using statistical mediation and moderation models. RESULTS: Eight hundred and sixty-four patients received neoadjuvant nab-paclitaxel (n= 437) or sb-paclitaxel (n = 427); nab-paclitaxel was superior for pCR (20.8% versus 12.9%, P = 0.002). pCR was higher for RS >25 versus RS ≤25 (16.0% versus 8.4%, P = 0.021) and for ET non-response versus ET response (15.1% versus 6.0%, P = 0.027); no factors were predictive for the relative efficacy of nab-paclitaxel versus sb-paclitaxel. Patients with pCR had longer distant disease-free survival [dDFS; hazard ratio 0.42, 95% confidence interval (CI) 0.20-0.91, P = 0.024]. Despite favorable prognostic association of RS >25 versus RS ≤25 with pCR (odds ratio 3.11, 95% CI 1.71-5.63, P ≤ 0.001), higher RS was unfavorably associated with dDFS (hazard ratio 1.03, 95% CI 1.01-1.05, P = 0.010). CONCLUSIONS: In high-risk HR+/HER2- EBC, neoadjuvant nab-paclitaxel q1w appears superior to sb-paclitaxel q2w regarding pCR. Combining RS and ET response assessment appears to select patients with highest pCR rates. The disadvantage of higher RS for dDFS is reduced in patients with pCR. These are the first results from a large neoadjuvant randomized trial supporting the use of RS to help select patients for neoadjuvant chemotherapy in high-risk HR+/HER2- EBC.

The role of transvaginal ultrasonography for detecting ovarian cancer in an asymptomatic screening population: a systematic review.

INTRODUCTION: The purpose of this study was to systematically analyze the effect of transvaginal ultrasonography in an asymptomatic female population as an annual screening procedure with regard to mortality data. Studies were evaluated descriptively on their strengths and weaknesses considering the methods and results. METHODS: We evaluated 632 international studies by selecting only randomized controlled trials (RCTs). Three RCTs concerning transvaginal ultrasonography were found, performed in Japan, the USA, and Great Britain. DISCUSSION: Currently, no clear recommendation for the screening for ovarian cancer in an asymptomatic population can be given based on these three studies. The authors could not show a change in mortality using transvaginal ultrasonography for annual screening. CONCLUSION: An annual palpation does not offer a beneficial effect. The development of new ultrasound machines with higher image resolution in combination with a well-standardized algorithm for ovarian cancer in upcoming years might provide an improvement regarding mortality. The current studies do not show a benefit in screening an asymptomatic population annually with transvaginal ultrasonography, but the most recent publication showed a trend toward lower mortality in patients who underwent screening after 7-14 years of follow-up. Nevertheless, all three heterogeneous RCTs had weaknesses in their methods and therefore they neither contradict the general recommendation for screening in an asymptomatic population nor do they support it.

Long-term follow-up and quality of life in patients with intracranial germinoma.

Intracranial germinomas are fairly rare tumors occurring mostly in children or young adults with a comparatively good prognosis. Radiation is the preferred treatment of choice for this diagnosis. It has been thoroughly studied to what extent radiation doses and fields can be limited in order to avoid side effects in these young patients. The role of chemotherapy remains unclear, whereas surgery is limited to biopsy for proof of histology. Regarding the good overall survival rate, quality of life is a significant aspect to consider in these patients. We present a single institution analysis of patients with intracranial germinoma and analyze the long-term outcome with special regard to quality of life. Thirty-three patients with intracranial germinomas were analyzed by chart review, telephone interview, and neurological assessment. Additionally, a survey on quality of life was performed. The 10-year overall survival rate was 82.1 % at a mean follow-up of 141 (22-306) months. Three quarters (76 %) of the patients reached a favorable neurological outcome on the Modified Rankin Scale (mRS 0-2). However, the self-reported quality of life was significantly worse in germinoma patients compared with a healthy control group (p < 0.001). Surgical resection of the tumor led to no improvement regarding overall survival, neurological outcome, and quality of life. In terms of cognitive functioning, patients with tumor resection were significantly more impaired than biopsied patients (p = 0.04). Although germinomas are efficiently treatable tumors, the restrictions in quality of life in these often young patients are considerable, including financial difficulties. There seems no justification for tumor resection in newly diagnosed cases suspicious for germinoma as the cognitive outcome is worse than in biopsied patients, and there is no effect on overall survival.

The use of complementary and alternative medicine by women transitioning through menopause in Germany: results of a survey of women aged 45-60 years.

OBJECTIVES: To describe prevalence rates of complementary and alternative medicine therapies (CAM) for the relief of menopausal complaints among German women. Furthermore, to investigate the perceived effectiveness of these therapies. DESIGN: A self-administered questionnaire was sent to 9785 randomly selected women in Germany aged between 45 and 60 years. RESULTS: A total of 1893 (19.3%) questionnaires have been sent back. The mean age of all participants was 52.6±4.3 years. 81% (n=1517) of the responding women stated that they had experienced menopausal complaints at least once. Symptoms ranged from vasomotor symptoms, including hot flushes and night sweats, in 71.2% of cases, to bladder problems in 42.7%. The average symptom score (MRS II total score, range 1-44) among the respondents was 12.76±9.6. More than half (56%; n=1049/1872) of the responding women had used some form of therapy to alleviate their symptoms at least once. The majority of women undertaking a therapy (64.8%; n=679/1049) had used only CAM interventions (either one or more type of CAM), 14.2% (n=149) had used hormone replacement therapy (HRT) only, while 21.1% (n=221/1049) had tried both CAM and HRT. Popular CAM interventions by the respondents were an alteration of lifestyle (28.7%), St. John's wort (18.3%) and homoeopathy (14.9%). An alteration in lifestyle was rated as the most effective CAM treatment with 84.9% (n=457). Other treatments like hormone yoga (79.2%; n=42), homoeopathy (73.7%; n=205) and TCM (59.1%; n=94) were also perceived to be effective. Phytoestrogens were rated as the most ineffective (45.5%; n=50). CONCLUSION: CAM interventions to alleviate menopausal complaints are popular among German women, with 48.2% (n=900/1872) of respondents reporting having used CAM either alone or in combination with HRT. However, the users rated the effects of CAM differently, with some reporting CAM to be highly effective, while others indicate lower effectiveness. Nevertheless, women with a significantly higher symptom scoring tend to use both CAM and a conventional therapy (HRT).

Attitude of German women towards hormone therapy: results of a lay survey.

OBJECTIVE: Hormone therapy (HT) use has experienced a substantial change since publication of Women's Health Initiative (WHI) controlled trial. We aimed to investigate the attitude towards HT in German women aged 45-60 years. STUDY DESIGN: A questionnaire was sent to 9785 randomly selected women in Germany aged between 45 and 60 years. RESULTS: Response rate was 19.3% (n = 1,893). Of those, 81% experienced climacteric symptoms. Vasomotor symptoms were most frequently reported (71.2%; n = 1332). Of the respondents, 19.7% (n = 369) used HT. The most frequently mentioned benefits of HT were the improvement of climacteric complaints (71.2%; n = 1346), followed by the relief of osteoporosis (37.2%; n = 697) and the "anti-aging" effect (16.3%; n = 305). Breast cancer was stated as the main risk (64.9%; n = 1215), closely followed by weight gain (53.4%; n = 1000) and thromboembolism (48%; n = 898). About 44% of the women who has been advised by gynaecologists choose a HT, whereas this rate dropped down to 14.3% and 11.3% for women who have been advised by friends or media. CONCLUSION: German women were generally aware of the main risks and benefits of HT. "More informed" women appear to be more likely to use HT compared to "less informed" women. The media produces negative impression of HT.

Increased osteoblast and osteoclast indices in individuals with systemic mastocytosis.

UNLABELLED: Indolent systemic mastocytosis (ISM) can trigger bone loss. However, the clinical relevance of different mast cell infiltration patterns for bone remains to be clarified. Here, we report increased bone turnover in individuals with ISM, and its extent is rather related to the type of mast cell distribution within the bone marrow than to the presence or absence of cutaneous manifestations. INTRODUCTION: It is well established that ISM can trigger osteopenia or osteoporosis. However, neither the clinical relevance of the infiltration pattern of mast cells within the bone marrow nor the impact of the presence or absence of cutaneous mast cell infiltration has been elucidated. METHODS: We retrospectively analysed 300 cases with histologically proven ISM of the bone marrow and performed quantitative histomorphometry for a subgroup of 159 patients that did not receive any treatment before the biopsies were taken. Most importantly, since 66 % of the patients displayed ISM without the characteristic skin lesions, we were able to compare ISM with or without cutaneous manifestation. RESULTS: We found that both forms of ISM were not only characterized by a decreased trabecular bone mass but also by an increased number of osteoclasts and osteoblasts. Interestingly, when we analysed these data in relation to mast cell distribution, we found that the bone cell numbers in cases with mast cell granulomas were significantly increased compared to cases with diffuse mast cell distribution. Moreover, evidence of increased bone turnover was also found in 16 patients displaying osteosclerosis. CONCLUSION: Based on the largest cohort of bone biopsies from patients with ISM analysed so far, we could demonstrate high bone turnover, more specifically increased osteoblast and osteoclast numbers and surface indices, as a cause of the skeletal changes. Moreover, the severity of the bone disease is presumably rather dependent on the amount of mast cells and their distribution within the bone marrow irrespective of the presence or absence of cutaneous involvement.

Prognostic impact of the time interval between surgery and chemotherapy in advanced ovarian cancer: analysis of prospective randomised phase III trials.

BACKGROUND AND AIMS: Surgery followed by platinum-taxane chemotherapy is the current standard approach to treat advanced ovarian cancer. The impact of the time interval between surgery and initiation of chemotherapy for clinical outcome has not been clarified yet. METHODS: Individual patient data analysis of 3326 patients from three prospective randomised phase III trials conducted between 1995 and 2002 to investigate platinum-taxane based chemotherapy regimens in advanced ovarian cancer. Time to chemotherapy (TTC) was analysed and correlated with outcome. RESULTS: Median TTC was 19 days (range 1-56). The effect of TTC differed significantly for patients with or without residual disease for progression-free (PFS; interaction p=0.004) and for overall survival (OS; interaction p=0.028). A delayed start of chemotherapy was associated with earlier disease recurrence (HR 1.038, 95% CI 0.973; 1.106, p=0.257 per week delay) and a significantly decreased OS (HR 1.087, 95% CI 1.005; 1.176 p=0.038) in patients with no residual tumour after surgery. In contrast, in patients with residual disease, a longer TTC was significantly associated with later progression (HR 0.931, 95% CI 0.895; 0.969, p<0.001) and no effect towards OS (HR 0.983, 95% CI 0.940; 1.028, p=0.452). CONCLUSIONS: Our results provide evidence that early initiation of chemotherapy might result in slightly improved survival in patients with complete cytoreduction while patients with residual disease after surgery did not benefit from earlier chemotherapy. A prospective study randomising patients to different time intervals could clarify the definitive relevance of the time between surgery and chemotherapy.

Impaired bone mineralization accompanied by low vitamin D and secondary hyperparathyroidism in patients with femoral neck fracture.

SUMMARY: Although it is well established that a decrease in bone mass increases the risk of osteoporotic fractures, the proportion of fractures attributable to areal bone mineral density (BMD) is rather low. Here, we have identified bone mineralization defects together with low serum 25-hydroxyvitamin D (25-(OH) D) levels as additional factors associated with femoral neck fractures. INTRODUCTION: Osteoporotic fractures of the femoral neck are associated with increased morbidity and mortality. Although it is well established that a decrease in bone mass increases the risk of osteoporotic fractures, the proportion of fractures attributable to areal BMD is rather low. To identify possible additional factors influencing femur neck fragility, we analyzed patients with femoral neck fracture. METHODS: We performed a detailed clinical and histomorphometrical evaluation on 103 patients with femoral neck fracture including dual-energy X-ray absorptiometry, laboratory parameters, and histomorphometric and bone mineral density distribution (BMDD) analyses of undecalcified processed biopsies of the femoral head and set them in direct comparison to skeletal healthy control individuals. RESULTS: Patients with femoral neck fracture displayed significantly lower serum 25-(OH) D levels and increased serum parathyroid hormone (PTH) compared to controls. Histomorphometric analysis revealed not only a decreased bone volume and trabecular thickness in the biopsies of the patients, but also a significant increase of osteoid indices. BMDD analysis showed increased heterogeneity of mineralization in patients with femoral neck fracture. Moreover, patients with femoral neck fracture and serum 25-(OH) D levels below 12 µg/l displayed significantly thinner trabecular bone. CONCLUSION: Taken together, our data suggest that impaired bone mineralization accompanied by low serum 25-(OH) D levels is of major importance in the etiology of femoral neck fractures. Therefore, balancing serum 25-(OH) D levels and thereby normalizing PTH serum levels may counteract pronounced mineralization defects and might decrease the incidence of femoral neck fractures.

Comparison of values in critically ill patients for global end-diastolic volume and extravascular lung water measured by transcardiopulmonary thermodilution: A metaanalysis of the literature

Introduction: Hemodynamic parameters such as the global end-diastolic volume index (GEDVI) and extravascular lung water index (EVLWI), derived by transpulmonary thermodilution, have gained increasing interest for guiding fluid therapy in critically ill patients. The proposed normal values (680-800ml/m2 for GEDVI and 3-7ml/kg for EVLWI) are based on measurements in healthy individuals and on expert opinion, and are assumed to be suitable for all patients. We analyzed the published data for GEDVI and EVLWI, and investigated the differences between a cohort of septic patients (SEP) and patients undergoing major surgery (SURG), respectively. Methods: A PubMed literature search for GEDVI, EVLWI or transcardiopulmonary single/double indicator thermodilution was carried out, covering the period from 1990 to 2010. Intervention: Meta-regression analysis was performed to identify any differences between the surgical (SURG) and non-surgical septic groups (SEP). Results: Data from 1925 patients corresponding to 64 studies were included. On comparing both groups, mean GEDVI was significantly higher by 94ml/m2 (95%CI: [54; 134]) in SEP compared to SURG patients (788ml/m2 95%CI: [762; 816], vs. 694ml/m2, 95%CI: [678; 711], p<0.001). Mean EVLWI also differed significantly by 3.3ml/kg (95%CI: [1.4; 5.2], SURG 7.2ml/kg, 95%CI: [6.9; 7.6] vs. SEP 11.0ml/kg, 95%CI: [9.1; 13.0], p=0.001).Conclusions: The published data for GEDVI and EVLWI are heterogeneous, particularly in critically ill patients, and often exceed the proposed normal values derived from healthy individuals. In the group of septic patients, GEDVI and EVLWI were significantly higher than in the group of patients undergoing major surgery. This points to the need for defining different therapeutic targets for different patient populations (AU)

Introducción: Parámetros hemodinámicos como el índice de volumen diastólico final global (GEDVI) y el índice de agua pulmonar extravascular (EVLWI), obtenidos mediante termodilución transpulmonar, suscitan un interés creciente como guía de la terapia de fluidos en pacientes críticamente enfermos. Los valores normales propuestos (680-800ml/m2 para el GEDVI y 3-7ml/kg para el EVLWI) se basan en mediciones realizadas a individuos sanos y en la opinión de expertos, y se asume que son adecuados para todos los pacientes. Analizamos los datos publicados sobre el GEDVI y el EVLWI e investigamos las diferencias entre una cohorte de pacientes septicémicos (SEP) y pacientes sometidos a cirugía mayor (SURG) respectivamente. Métodos: Se realizó una búsqueda bibliográfica en PubMed de GEDVI, EVLWI o termodilución trasncardiopulmonar de indicador único/doble referida al periodo comprendido entre 1990 y 2010. Intervenciones: Se realizó un análisis de metarregresión para identificar las diferencias entre los grupos quirúrgico (SURG) y no quirúrgico septicémico (SEP). Resultados: Se incluyeron los datos de 1925 pacientes correspondientes a 64 estudios. Al comparar ambos grupos, el GEDVI medio resultó ser significativamente (..) (AU)

Predictive value of HER2 serum levels in patients treated with lapatinib or trastuzumab -- a translational project in the neoadjuvant GeparQuinto trial.

BACKGROUND: We were able to demonstrate a predictive value of serum HER2 (sHER2) in patients receiving trastuzumab in the neoadjuvant GeparQuattro trial. However, the role of sHER2 in patients receiving neoadjuvant therapy (NT) with lapatinib is still unclear. METHODS: The neoadjuvant GeparQuinto trial compared trastuzumab vs lapatinib in addition to chemotherapy in HER2-positive primary breast cancer patients. The sHER2 levels were measured by enzyme-linked immunosorbant assay in 210 patients, of whom 109 (52%) patients received trastuzumab and 101 (48%) lapatinib at three different time points. RESULTS: Twenty-two percent of patients had elevated baseline sHER2 levels (>15 ng ml⁻¹). A decrease of sHER2 levels (>20%) in the trastuzumab and lapatinib-treated group during NT was seen in 44% and 24% of the patients, an increase of sHER2 levels (>20%) was seen in 6% and 41% of patients, respectively. Higher pre-chemotherapy sHER2 levels were associated with higher pathological complete remission (pCR) rates in the entire study cohort (OR 1.8, 95% CI 1.02-3.2, P=0.043). A decline of sHER2 levels (>20%) during NT was a predictor for pCR in the lapatinib-treated patient group (OR: 11.7, 95% CI 1.3-110, P=0.031). CONCLUSION: Results of this study demonstrate that sHER2 levels change differently during NT depending on the anti-HER2 treatment strategy. Elevated baseline sHER2 levels (>15 ng ml⁻¹) and a decrease of sHER2 levels (>20%) early after therapy initiation are both relevant criteria to predict response to lapatinib-based treatment.

Comparison of values in critically ill patients for global end-diastolic volume and extravascular lung water measured by transcardiopulmonary thermodilution: a meta-analysis of the literature.

INTRODUCTION: Hemodynamic parameters such as the global end-diastolic volume index (GEDVI) and extravascular lung water index (EVLWI), derived by transpulmonary thermodilution, have gained increasing interest for guiding fluid therapy in critically ill patients. The proposed normal values (680-800ml/m(2) for GEDVI and 3-7ml/kg for EVLWI) are based on measurements in healthy individuals and on expert opinion, and are assumed to be suitable for all patients. We analyzed the published data for GEDVI and EVLWI, and investigated the differences between a cohort of septic patients (SEP) and patients undergoing major surgery (SURG), respectively. METHODS: A PubMed literature search for GEDVI, EVLWI or transcardiopulmonary single/double indicator thermodilution was carried out, covering the period from 1990 to 2010. INTERVENTION: Meta-regression analysis was performed to identify any differences between the surgical (SURG) and non-surgical septic groups (SEP). RESULTS: Data from 1925 patients corresponding to 64 studies were included. On comparing both groups, mean GEDVI was significantly higher by 94ml/m(2) (95%CI: [54; 134]) in SEP compared to SURG patients (788ml/m(2) 95%CI: [762; 816], vs. 694ml/m(2), 95%CI: [678; 711], p<0.001). Mean EVLWI also differed significantly by 3.3ml/kg (95%CI: [1.4; 5.2], SURG 7.2ml/kg, 95%CI: [6.9; 7.6] vs. SEP 11.0ml/kg, 95%CI: [9.1; 13.0], p=0.001). CONCLUSIONS: The published data for GEDVI and EVLWI are heterogeneous, particularly in critically ill patients, and often exceed the proposed normal values derived from healthy individuals. In the group of septic patients, GEDVI and EVLWI were significantly higher than in the group of patients undergoing major surgery. This points to the need for defining different therapeutic targets for different patient populations.

[The effects of multimodal intervention for the primary prevention of cardiovascular diseases on depression, anxiety, and Type-D pattern: initial results of the randomized controlled PreFord trial]. / Effekte einer multimodalen Intervention zur Primärprävention kardiovaskulärer Krankheiten auf Depressivität, Angst und Typ-D-Muster: Erste Ergebnisse der randomisierten, kontrollierten PräFord-Studie.

Depression, anxiety, and Type-D pattern are associated with the earlier development and faster progression of cardiovascular disease (CVD). The aim of the randomized controlled PreFord trial was to improve multiple biological and psychosocial risk factors in the primary prevention of CVD. A total of 447 women and men with an ESC risk score >5% were randomly assigned to either multimodal or routine care groups. Somatic and psychosocial variables (HADS, DS-14) were assessed before and after the intervention, and annually for 2 years thereafter. The intervention showed no significant effects on the symptoms of depression, anxiety, and type D personality, either in the whole sample or in those with elevated scores at baseline. Thus, our study did not provide evidence that symptoms of depression, anxiety, or Type D personality can be effectively treated by multimodal behavioral interventions for the primary prevention of CVD.

EGFR gene copy number increase in vulvar carcinomas is linked with poor clinical outcome.

EGFR copy number increases have been frequently reported in cancer including vulvar carcinomas. Co-amplification of cancer genes plays an important role in the development of many tumour types. To better understand the effect of EGFR aberrations on vulvar cancer phenotype and patient prognosis, the authors analysed EGFR copy number changes using fluorescence in situ hybridisation and EGFR expression by immunohistochemistry in a tissue microarray containing 183 squamous cell carcinomas of vulva. Furthermore, the authors analysed the co-amplification frequency of EGFR with HER2, CCND1, MYC and PIK3CA, respectively. EGFR copy number increase was found in 39.3% of the tumours. Seventeen per cent of vulvar carcinomas showed EGFR high polysomy including 9% with amplification of the EGFR gene. Copy number gain of the EGFR locus was associated with non-basaloid phenotype (p=0.03), high-tumour stage (p<0.001), human papillomaviruse negativity of tumours (p=0.04) and the number of lymph node metastases (p=0.02). EGFR protein expression was statistically correlated to EGFR copy number increase (p<0.05). The observed co-amplification rate of EGFR with all four additionally examined oncogenes was much higher than statistically expected. There was a highly significant association between EGFR copy number increase and CCND1 amplifications (p<0.001) as well as the total number of gene amplifications (p=0.04). EGFR copy number gains were significantly related to unfavourable patient outcome in univariate analysis and multivariate Cox regression analysis. In conclusion, EGFR copy number increases are detectable in a substantial proportion of vulvar carcinomas with relationships to advanced tumour stages and the development of lymph node metastases. EGFR copy number aberrations are connected to other gene amplifications and probably define an human papillomaviruses-independent pathway in the development of vulvar carcinomas. These data support the potential utility of EGFR inhibitors as a therapeutic alternative in a subset of vulvar carcinomas.

Attitude of German gynecologists towards prescribing HRT before and after the WHI study.

OBJECTIVE: The publication of the Women's Health Initiative (WHI) randomized, controlled trial in 2002 resulted in a critical discussion on the risks and benefits of hormone replacement therapy (HRT). The present study aims to evaluate the attitude of German gynecologists regarding changes in the prescription of HRT over recent years. Method A questionnaire was sent to all 9589 German gynecologists in private practice in November 2010. RESULTS: The response rate was 2548 (26.6%). Whereas 82.2% of the responders stated that their advice for primary hormone therapy and alternative agents depended on the severity of symptoms, 9.1% of the responders would recommend HRT in the first place (male: 14.3%; female: 6.1%; p < 0.001). An age limit for hormone prescription was stated by 26.2%, with a mean age limit of 63 ± 5.3 years. An increasing number of patients and becoming more critical about HRT after the WHI was mentioned by 79.8%. Of the responding doctors, 43.9% found that their patients were badly informed by the media, 44.5% stated they were moderately or well (10.1%) informed, whereas only 1% considered their patients to be very well informed. HRT was prescribed for the relief of vasomotor symptoms by 97.4% of responders, making this the primary indication. This percentage decreased slightly to 92.6% between 2003 and 2008 (p < 0.001) and increased again to a similar level at the beginning of 2010 (96.7%, p < 0.05). CONCLUSION: German gynecologists generally have a positive attitude towards HRT, but find it important to focus on the evaluation of the risk-benefit ratio. The major barriers to prescription are multiple concerns of the patients resulting from non-objective media.

Health-related quality of life and patient-defined benefit of clobetasol 0.05% in women with chronic lichen sclerosus of the vulva.

BACKGROUND: This study investigates the health-related quality of life in patients with vulvar lichen sclerosus (LS) and the patient-defined therapeutic benefit of clobetasol. METHODS: A survey analysis of 96 women with LS after treatment with clobetasol was performed. Quality of life was assessed with the Skindex-29. The Patient Benefit Index (PBI) was used to determine the therapeutic benefit. RESULTS: The overall response rate was 59.2%. Quality of life was most impaired by somatic symptoms (scale 'Symptoms' score 3.2) and emotional stress (scale 'Emotions' score 3.1), while social interactions (scale 'Functioning' score 1.9) played an inferior role (p < 0.001). Primary therapeutic goals 'to have confidence in the therapy' and 'to be free of itching' were achieved in 73.2 and 69.0% of patients who indicated the goal applied to them. The global PBI score was 3.06. In 93.2% of patients it was >1, indicating a potential benefit from clobetasol. CONCLUSION: Topical clobetasol is of potential therapeutic benefit for patients with vulvar LS and might therefore improve quality of life.

Perioperative morbidity and outcome of secondary cytoreduction for recurrent epithelial ovarian cancer.

BACKGROUND: Despite radical surgical and chemotherapeutic treatment of ovarian cancer, the majority of patients develop recurrent disease. Secondary cytoreductive surgery can result in favourable outcome in selected patients, but information regarding feasibility, safety and perioperative outcome of these often complex procedures is limited. METHODS: Surgical parameters in patients with recurrent epithelial ovarian cancer selected for secondary cytoreduction were analysed and compared to patients undergoing primary cytoreduction. RESULTS: In total, 222 patients undergoing radical cytoreduction were analysed (48 patients for relapsed disease and 174 patients at primary diagnosis of advanced ovarian cancer). The range of surgical procedures was similar in both groups. In 48% of secondary cytoreductions 'optimal surgical results' (residual tumour <1 cm) were obtained and 33% of the patients had no residual disease compared to 82% and 58% at primary cytoreduction. There was no significant difference in perioperative complication rates. The duration of surgery was shorter and the number of transfused blood products was smaller at secondary cytoreduction (p < 0.001 and p = 0.001). CONCLUSION: Secondary cytoreduction in relapsed ovarian cancer is safe and feasible and perioperative outcome is not inferior compared to primary cytoreduction. Surgery-associated morbidity should represent a minor aspect in the selection and counselling of patients regarding treatment options for recurrent ovarian cancer.

Single nucleotide polymorphism in esophageal cancer related gene 1: an analysis in resected oral squamous cell carcinoma patients.

Esophageal cancer related gene 1 (ECRG1) is a novel candidate tumor suppressor gene in human esophageal squamous cells. Overexpression of ECRG1 protein inhibits tumor cell proliferation. Genetic polymorphisms in coding sequences of the gene may cause functional alterations of the gene product and be associated with higher cancer risk and disease phenotypes. A single nucleotide polymorphism (SNP) (Arg290Gln) found in the coding region of ECRG1 might play a role in susceptibility to esophageal squamous cell carcinoma. This study examined SNPs in ECRG1 in a similar tumor type (oral squamous cell carcinoma; OSCC) and investigated the relationship between SNPs in ECRG1 and the clinical outcome of patients with OSCC. DNA samples of 137 OSCC patients were analyzed for SNP genotypes Arg/Arg, Arg/Gln and Gln/Gln in the coding region (exon 8) of ECRG1. SNP genotypes Arg/Arg were found in 70 (51%), Arg/Gln in 60 (43%) and Gln/Gln in 7 (5%) patients. There was no significant association between genotypes and survival (p=0.77) or relapse free survival (p=0.32). The Gln/Gln genotype had the best survival (not significant) probably due to rare cases of SNP Gln/Gln genotype. Genotype Arg/Arg might be a potential negative prognostic marker in OSCC, but more studies with higher patient numbers are required.