ObjectiveSexual activity (SA) and functioning (SF) are important factors influencing quality of life (QoL). Anticancer treatment can cause or promote sexual dysfunctions. In this study we analyzed the SA, SF and QoL in patients after completion of treatment for breast cancer (BC) and ovarian cancer (OC).MethodsIn this retrospective multicenter study 396 BC patients and 93 OC patients aged between 18 and 70years were surveyed at least 24months after cancer diagnosis and compared to 60 healthy women. Data were collected through validated questionnaires (Sexual Activity Questionnaire, Female Sexual Function Index-d, EORTC Quality of Life Questionnaire-C30).Results45.9% of BC patients and 56.5% of OC patients reported SA. SF and well-being of sexually active BC patients were not influenced by the type and radicality of surgery or the administration of chemotherapy. Patients who received antihormonal therapy at the time of evaluation showed a lower frequency of SA (p=0.007), less satisfaction (p=0.003) and more discomfort during SA (p=<0.001) compared to healthy controls but no differences in experiencing orgasms, health status, QoL and global health status. In contrast, BC patients without antihormonal therapy showed only a higher discomfort score (p=0.028) than healthy controls and estimated their health status and QoL significantly better than patients who received antihormonal therapy (p=0006). In general, SA was associated with a better health status (p=0.007), a better QoL (p=0.004) and a better global health status (p=0.004) in BC patients. Sexually active OC patients showed no significant differences in SF, QoL and health status compared to healthy controls.ConclusionsCompared to healthy controls BC patients showed limitations in SF with a lower SA rate and more discomfort. Antihormonal therapy was an important factor influencing SF and well-being. Breast and OC survivors reported good physical and psychical health without differences in QoL and health status compared to controls. This might be explained by a change of perspective on life difficulties and altered priorities through a life threatening disease.

To compare operating time and blood loss in patients undergoing total laparoscopic hysterectomies (TLH) for benign conditions with either the Marseal™ IQ 5 mm (MS) or the Ligasure™ 5 mm (LS) vessel-sealing device.

The psychological and somatic strain in patients with chronic, recurrent herpes simplex virus- (HSV) infections is high. Standard diagnostics involve the evaluation of characteristic clinical symptoms, serologic testing and the direct detection of HSV in body fluids and tissues. Aciclovir is commonly used in the prevention and treatment of HSV-infections. Immunodeficient patients are more likely to get infected by HSV.

Etwa 4% der zervikalen Adenokarzinome sind villoglanduläre Adenokarzinome (VGA). Diese Sonderform soll im Vergleich zum herkömmlichen Zervixkarzinom eine sehr gute Prognose aufweisen. Ist daher ein nicht radikal-operatives Vorgehen vertretbar?

Less than 10 deliveries via cervicovaginal fistula (CVF) with closed cervical os were reported so far. In the majority of cases, the patients had a history of induced abortions. The CVF was usually recognized due to postpartum hemorrhage. The facilitating role of prostaglandins used for labor induction was supposed. In all cases, the babies remained unaffected by the delivery route. We report a new case of a 37-year-old gravida 2, para 0, with a history of a paracervical tear following a first trimester abortion 11 years ago. The abortion and the laceration were not reported in the current obstetrical documentation. After labor induction using oral misoprostol in the 41 + 5 weeks of pregnancy, the patient delivered a healthy baby through a left-sided CVF, which imposed as bleeding paracervical laceration, 6 cm in diameter, extending to the vaginal fornix in the 3 o'clock position. The cervical os was only 1-1.5 cm dilated and imposed as an inelastic band ("squid ring") in the 9 o'clock position. The laceration was sutured under spinal anesthesia. The patient recovered quickly, and the postpartum hemoglobin drop was 2.8 g/dl. In conclusion, the possibility of CVF should be considered in women with a history of induced abortion.

BACKGROUND/AIM The pro-angiogenic Cyr61 protein has been associated with tumorigenesis and cancer progression in different gynecological carcinomas. In this study, we evaluated the potential impact and clinical relevance of Cyr61 expression in patients with primary non-metastatic cervical cancer (CC). PATIENTS AND METHODS Cyr61 expression was assessed in tissue specimen of 48 patients with primary CC by immunohistochemical analysis. Expression levels were scored and correlated to clinico-pathological factors and outcome data. RESULTS High Cyr61 expression levels were present in 54.2% of CC tissues. Associations with histological grade (p=0.030), depth of tumor invasion (p=0.007) and GOG score (p=0.027) were observed. Patients who overexpressed Cyr61 displayed an increased death rate (30.8% vs. 18.2%) and a decreased 5-year-survival (76.9% vs. 86.4%). CONCLUSION Our data indicate a potential functional impact of Cyr61 in development and the progression of CC. The definite tumor-relevant function (suppressive/promoting) of Cyr61 in CC and the prognostic relevance of Cyr61 overexpression has to be evaluated in larger cohorts.

BACKGROUND:The effective utilization of staff resources is of decisive importance for the adequate, appropriate, and economical delivery of hospital services. The goal of this study was to determine the distribution of working time among doctors in a German university hospital-in particular, in terms of type of activities and time of day.METHODS:The distribution of working time was determined from 14-day samples taken in seven clinical departments of the Medical Center-University of Freiburg. In each 14-day sample, the activities being carried out at multiple, randomly chosen times were recorded.RESULTS:A total of 250 doctors (participation rate: 83%) took part in the study. A total of 20 715 hours of working time was analyzed, representing twelve years of full-time employment. Overall, 46% of working time in the inpatient sector was spent in direct contact with patients, with relevant differences among the participating clinical departments: for instance, the percentage of time taken up by patient contact was 35% in pediatrics and 60% in oral and maxillofacial surgery. Patient contact was highest (over 50% overall) in the period 8 a.m. to 12 noon.CONCLUSION:The amount of working time taken up by activities other than direct patient contact was found to be lower than in previous studies. It remains unclear what distribution of working time is best for patient care and whether it would be possible or desirable to increase the time that doctors spend in direct contact with patients.

Objective: The aim of this study was to calculate the validity parameters of the Digene Hybrid Capture 2 (HC2) high-risk human papillomavirus DNA test with and without cytology in the follow-up examinations after laser treatment of the transformation zone or large loop excision of the transformation zone (LLETZ) for cervical intraepithelial neoplasia (CIN). Methods: We performed a standardized follow-up examination in 113 postlaser and 153 post-LLETZ patients in our colposcopy clinic. Routine cytology, HC2 tests, and colposcopically-guided cervical biopsies were performed and sensitivity, specificity, and positive and negative predictive values were calculated using the histological cervical biopsy result as the criterion standard. Results: After a median follow-up time of 25.5 months, the overall posttreatment recurrence/persistence rate of CIN2 or higher (CIN 2+) was 24% after laser and 12.4% after Post-LLETZ treatment. Hybrid Capture 2 alone had a sensitivity/NPVof 70/88% in post-laser and 70/93% in post-LLETZ patients. Cytology alone had a sensitivity/NPV for CIN 2+ of 48/84% in post-laser and 58/91% in post-LLETZ patients. Combined testing of HC2 with cytology had a sensitivity/NPV of 81/92% in postlaser and 88/95% in post-LLETZ patients. Discussion: In this test of cure study, combined testing of cytology with HC2 resulted in a high sensitivity and NPV. Hybrid Capture 2 and cytology-negative women may safely return to routine recall. Cytology alone is not an adequate follow-up strategy in postlaser patients.

Frühes Therapieansprechen auf eine neoadjuvante Chemotherapie (NACT) beim Mammakarzinom ist insbesondere bei Patientinnen mit tripelnegativen (TNBC) mit einer hohen Rate an pathologischer Komplettremission assoziiert. Nichtkodierende RNAs (ncRNAs), z.B. microRNAs, sind beim Mammakarzinom an onkogenen und tumorsuppressiven Prozessen beteiligt. Diese in-vitro-Studie untersucht das Potential von ncRNAs als neuartige Biomarker bezüglich des Therapieansprechens auf die NACT mit Fokus auf das TNBC.

Tumor resistance to endocrine therapy triggers estrogen-independent cancer progression, which is a major obstacle to the successful treatment of hormone receptor positive breast cancer (BC). The underlying molecular mechanisms of endocrine resistance are not fully understood yet. The matricellular protein cysteine-rich angiogenic inducer 61 (Cyr61) is associated with tumor invasiveness and the induction of tumorigenesis in various malignancies in vivo and the induction of estrogen-independence and endocrine therapy resistance in BC. The present study evaluated the potential effects and clinical relevance of Cyr61 expression levels in 67 patients with primary non-metastatic BC. Immunohistochemical analysis of formalin-fixed paraffin-embedded tissue sections was performed, and the association between Cyr61 protein expression and clinicopathological factors and survival was analyzed. Cyr61 overexpression was revealed to be significantly associated with a positive estrogen receptor (ER)/progesterone receptor (PR) status (P=0.016) and to the molecular subtype of BC (P=0.039). Compared with patients without Cyr61 overexpression, patients with Cyr61 overexpression exhibited an increased recurrence rate (30.6 vs. 22.6%) and decreased long-term survival (10-year overall survival, 62.9 vs. 69.7%); however, these associations did not reach statistically significant levels in Cox regression model analysis. Similar results were identified in the subgroup analysis of patients with ER/PR positive BC. These results indicate that Cyr61 serves a role in the development of endocrine therapy resistance in BC and is thus a potential therapeutic target to overcome endocrine therapy resistance. However, additional long-term survival analyses with large patient populations are required.

In recurrent ovarian cancer (ROC), there is a high demand on effective therapies with a mild toxicity profile. Treosulfan is an alkylating agent approved as oral (p.o.) and intravenous (i.v.) formulation for the treatment of recurrent ovarian cancer. Data on safety and efficacy for either formulation are rare. For the first time we conducted a randomized phase III study comparing both formulations in women with ROC.Patients having received at least two previous lines of chemotherapy were randomly assigned to one of two treatment arms: treosulfan i.v. 7000 mg/m2 d1 q4w or treosulfan p.o. 600 mg/m2 d1-28 q8w. Primary endpoint was safety regarding hematological and gastrointestinal toxicity grade III/IV, secondary endpoints were other toxicities, clinical benefit rate (CBR), time to progression (TTP), overall survival (OS) and quality of life.250 patients were treated with treosulfan i.v. (128) or treosulfan p.o. (122). In general treosulfan therapy was well tolerated in both treatment arms. Leukopenia grade III/IV occurred significantly more frequently in the p.o. arm (3.9% i.v. arm, 14.8% p.o. arm, p = 0.002). Other toxicities were similar in both arms. CBR was comparable between arms (41.4% i.v. arm, 36.9% p.o. arm). No difference in TTP (3.7 months i.v. arm, 3.5 months p.o. arm) or OS (13.6 months i.v. arm, 10.4 months p.o. arm, p = 0.087) occurred.Given the safety and efficacy results treosulfan is an acceptable option for heavily pretreated OC patients. Regarding the toxicity profile the i.v. application was better tolerated with less grade III and IV toxicities.

Due to their post-transcriptional regulatory impact on gene expression, microRNAs (miRNA, miRs) influence decisively cellular processes of differentiation, proliferation and apoptosis. In oncogenic pathways various miRNAs exert either oncogenic or tumor suppressor activities in a stage-specific manner. Dysregulation of miRNA expression pattern has been associated with several human cancers including endometrial cancer (EC). In the present study, expression profile alterations of EC associated secreted miRNAs were determined under the microenvironmental stress situations hypoxia and acidosis occurring in tumor progression and metastasis. The potential influence of hypoxia and acidosis vs. control conditions on the expression levels of 24 EC-relevant miRNA types was quantitatively accessed via real-time PCR in three established EC in vitro models. Expression data were analyzed statistically. In vitro application of hypoxia resulted in downregulation of miR-15a, miR-20a, miR-20b and miR-128-1 in Ishikawa cells (type I EC) and upregulation of miR-21 in EFE-184 cells (type I EC). Acidosis triggered upregulation of tumor promoting miR-125b in AN3-CA cell (type II EC), whereas in Ishikawa cells (type I EC) miRNAs with tumor suppressive function were found altered in divergent directions, both up- (let-7a) and down- (miR-22) regulated. Our current findings emphasize the functional importance of secreted miRNAs in the immediate response of EC cells to exogenic stress situations such as the typical tumor epiphenomena hypoxia and acidosis. Focusing on the specific potential of secreted, thus circulating miRNA molecules, alterations in expression levels not only influence intracellular gene expression and signaling cascades, but also transfer the induction of (tumor)biological cellular changes to adjacent cells.

Purpose: MicroRNAs have been identified as crucial regulators of carcinogenic pathways. Micro environmental alterations such as hypoxia and acidosis frequently accompany tumor progression and metastasis. Thereto expression profiles of 24 different microRNAs, exhibiting oncogenic as well as tumor suppressor functions, were investigated under the influence of these two exogenic stimuli in endometrial cancer (EC) in vitro.

There is increasing evidence that not only the way of data acquisition but also the design of data visualization (i.e., the format) has impact on the quality of pathology reports. Therefore, we investigated the correlation between the format of pathology reports and the amount as well as the detection time of transmitted data. All reports of oncological breast resection specimens referred to the Institute for Surgical Pathology, University Medical Center Freiburg, between 2003 and 2011 (n = 4181) were classified into descriptive reports (DR, n = 856), structured reports (SR, n = 2455), or template-based synoptic reports (TBSR, n = 870). The reports were screened regarding the content of nine organ-specific essential data. The amount of recorded essential data per report was summarized in an essential data score (EDS) and the format types were statistically compared regarding their EDS. Additionally, we measured the time a gynecologist needed to detect all nine essential data within a subset of reports and compared the format types regarding the detection times statistically. A full-score EDS of 9 was seen in 28.4 % of all reports, in 4 % of DRs, in 21.4 % of SRs, and in 72.3 % of TBSRs (p < 0.0001). Median EDS of DRs was 7, of SRs 8, and of TBSRs 9 (p < 0.0001). Data regarding tumor localization, tumor size, specific grading, angioinvasion, hormone receptor status, and additional findings were mentioned more frequently in TBSRs compared to other format type reports with a statistically highly significant difference (p < 0.0001). Mean data detection time decreased significantly from 26 to 20 and 14 s in DRs, SRs, and TBSRs, respectively. Our results clearly show that due to the use of TBSRs reporting of oncological breast resection specimens are improved regarding the content of essential data and the clarity of the data layout resulting in a rapid detection of essential data by clinicians.

Introduction:The gastrin-releasing peptide receptor (GRPR) is overexpressed in breast cancer.The present study evaluates GRPR imaging as a novel imaging modality in breast cancer by employing positron emission tomography (PET) and the GRPR antagonist 68 Ga-RM2.Methods: Fifteen female patients with biopsy confirmed primary breast carcinoma (3 bilateral tumors; median clinical stage IIB) underwent 68 Ga-RM2-PET/CT for pretreatment staging.In vivo tumor uptake of 68 Ga-RM2 was correlated with estrogen (ER) and progesterone (PR) receptor expression, HER2/neu status and MIB-1 proliferation index in breast core biopsy specimens.Results: 13/18 tumors demonstrated strongly increased 68 Ga-RM2 uptake compared to normal breast tissue (defined as PET-positive).All PET-positive primary tumors were ER-and PR-positive (13/13) in contrast to only 1/5 PET-negative tumors.Mean SUV MAX of ER-positive tumors was 10.6±6.0 compared to 2.3±1.0 in ER-negative tumors (p=0.016).In a multivariate analysis including ER, PR, HER2/neu and MIB-1, only ER expression predicted 68 Ga-RM2 uptake (model: r 2 =0.55, p=0.025).Normal breast tissue showed inter-and intraindividually variable, moderate GRPR binding (SUV MAX 2.3±1.0), while physiological uptake of other organs was considerably less except pancreas.Of note, 68 Ga-RM2-PET/CT detected internal mammary lymph nodes with high 68 Ga-RM2 uptake (n=8), a contralateral axillary lymph node metastasis (verified by biopsy) and bone metastases (n=1; not detected by bone scan and CT).Conclusion: Our study demonstrates that 68 Ga-RM2-PET/CT is a promising imaging method in ER-positive breast cancer.In vivo GRPR binding assessed by 68 Ga-RM2-PET/CT correlated with ER expression in primary tumors of untreated patients.

Introduction: Lesions of uncertain malignant potential (B3) represent a heterogeneous group with an overall risk for malignancy of 9.85-35.1% after total resection. Positive predictive values (PPV) for malignancy vary depending on B3 subtype.The aim of this study was to evaluate the PPV for malignancy in B3 lesions and to determine the clinical significance of atypia-dependent sub-classification (a = without epithelial atypia; b = with epithelial atypia) of B3 into B3a and B3b and papillary lesions (PL) in PLa and PLb.Methods: 219 patients with histopathologically proven B3 lesions on core needle/vacuum-assisted biopsy who subsequently underwent diagnostic excision biopsy were included in this study. PPVs for malignancy were reported for B3 in general and all B3 sub-categories. Logistic regression analysis identified associations between B3-subgroups and outcome after excision biopsy as well as the impact of clinical and diagnostic findings on excision diagnosis.Results: The overall PPV rate was 10.0% (22/219). Excision histology exhibited a higher malignancy rate in PLb (2/7; PPV: 28.6%) than in PLa (6/127; PPV: 4.7%) (p = 0.057) and in B3b (12/50; PPV: 24.0%) compared to B3a category (8/165; PPV: 4.8%) (p < 0.001).Discussion: These findings support the necessity of B3 lesion sub-classification into B3a and B3b and of PL into PLa and PLb when considering epithelial atypia. The determination of atypia status represents a relevant factor in risk-stratification for clinical management of B3 lesions. Should future studies using the sub-classification of PL confirm these results, observation may be a safe option for the clinical management of patients with asymptomatic PLa lesions. (C) 2016 Elsevier Ltd. All rights reserved.

PURPOSE:Expression profile alterations of nine breast cancer (BC)-associated secreted microRNAs (miRs) were determined under microenvironmental alterations occurring in tumour progression, metastasis or specific oncological treatment modalities. Thereto, the potential influence of the exogenic stimuli hypoxia, acidosis and hyperthermia was investigated in vitro.MATERIAL AND METHODS:Four established BC cell lines were applied as in vitro BC model systems. Quantitative analyses of secreted microRNA specimens were performed by RNA isolation from cell culture supernatant and subsequent real-time PCR in cells under physiological versus hypoxic, acidic or hyperthermia conditions.RESULTS:The in vitro application of exogenic stimuli hypoxia, extracellular acidosis and hyperthermia caused heterogeneous expression alterations for the investigated secreted miRNA phenotypes. The majority of relevant exogenic stimuli-dependent microRNA expression alterations were restricted to single events displaying distinct cell type and stimulus dependent correlations only. Most remarkably, hyperthermia triggered a uniform significant down-regulatory effect on the expression levels of the three secreted microRNAs miR-10b, miR-15b and miR-139, respectively. The marked decrease in miR-10b and miR-15b levels was detectable in all four, while miR-139 was found significantly reduced in three out of four BC cell lines.CONCLUSION:Hyperthermia-dependent down-regulatory influence on three distinct BC-related microRNAs in vitro generates translational aspects for clinical BC treatment, since the identified microRNAs miR-10b, miR-15b and miR-139 are known to have oncogenic as well as tumour suppressor functions in BC. However, an evaluation regarding the potential impact of microRNA-related hyperthermia-dependent alterations for innovative BC treatment approaches demands further analysis including in vivo data.

INTRODUCTION:There is only limited data from clinical practice on the relevance of body mass index (BMI) on pathologic complete response (pCR) following neoadjuvant chemotherapy (NAC) in patients with breast cancer (BC). PATIENTS AND METHODS:The impact of BMI on pCR and survival outcome was examined in 324 patients with primary non-metastatic BC. An additional meta-analysis was performed on the current data and relevant previously published studies in clinical practice. RESULTS:Multivariable regression analysis identified lymph vascular invasion (odds ratio [OR], 0.05; 95% confidence interval [CI], 0.01-0.18; P = .0000), grading 3 (OR, 3.12; 95% CI, 1.59-6.12; P = .0009), and HER2/neu status (OR, 4.76; 95% CI, 1.86-12.18; P = .011) as independent factors for pCR after NAC. There was no association between pCR and continuous or categorical BMI. Various additional subgroup analyses of molecular BC subtypes (triple-negative, luminal-like, HER2-luminal, HER2-like) and BMI also showed no association. These findings were confirmed by the meta-analysis. Except for one subgroup analysis in which overweight and obese patients were combined as one group, no association between BMI and pCR as well as survival outcome was found. CONCLUSIONS:BMI was not established as a relevant clinical factor. Only lymph vascular invasion, grading 3, luminal-like, and HER2/like BC subtype showed predictive and prognostic impact in patients with BC receiving NAC.