[Predictors of the Utilization and Waiting Period Before Starting an Oncological Rehabilitation after Breast Cancer]. / Prädiktoren der Inanspruchnahme und des Beginns einer onkologischen Rehabilitation nach Brustkrebs.

PURPOSE: This study explores the sociodemographic, medical and work-related factors leading to a participation in an in-house rehabilitation measure after primary treatment for breast cancer. METHODS: The prospective multi-center study is based on a written survey with employed breast cancer patients who were recruited at 11 breast cancer centers in Lower Saxony, Germany. Predictors of participation were examined by logistic regression, predictors of the time period before starting the rehabilitation by linear regression. RESULTS: 409 patients returned their questionnaires at all three time-points. Response rates were 80,1% 3 weeks after surgery (t0), 95,2% 6 months after surgery (t1) and 89,9% one year after surgery (t2). Altogether, 294 patients (72%) participated in the rehabilitation measure. Respondents, 90% of whom participated in rehabilitation before returning to work, began their rehabilitation on average 21 weeks after primary surgery. They showed an increased probability of participation if they had indicated the need to clarify their job situation (OR=2,74, p<0,01), or if their answers displayed a detrimental relation between effort and reward at work (OR=3,89, p<0,05). At the same time, higher age, a higher level of school education (OR=4,23) and reduced physical health (OR=0,94, p<0,01) increased the chance for breast cancer patients to take part in oncological rehabilitation. The starting point of rehabilitation was only predictable by medical treatments: adjuvant chemotherapy (ß=0,492, p≤0,001), additional surgery (ß=0,112, p<0,05), and radiation therapy within the second half year after primary surgery (ß=0,20; p<0,001) led to a postponement. CONCLUSION: This study shows that an increased need of breast cancer patients for medical and socio-psychological support leads to their participation in an in-house rehabilitation and thus underlines the necessity of these institutions. Women with an impaired psychological health should be given extra attention.

Free radicals induced by sunlight in different spectral regions - in vivo versus ex vivo study.

Sunlight represents an exogenous factor stimulating formation of free radicals which can induce cell damage. To assess the effect of the different spectral solar regions on the development of free radicals in skin, in vivo electron paramagnetic resonance (EPR) investigations with human volunteers and ex vivo studies on excised human and porcine skin were carried out. For all skin probes, the ultraviolet (UV) spectral region stimulates the most intensive radical formation, followed by the visible (VIS) and the near infrared (NIR) regions. A comparison between the different skin models shows that for UV light, the fastest and highest production of free radicals could be detected in vivo, followed by excised porcine and human skin. The same distribution pattern was found for the VIS/NIR spectral regions, whereby the differences in radical formation between in vivo and ex vivo were less pronounced. An analysis of lipid composition in vivo before and after exposure to UV light clearly showed modifications in several skin lipid components; a decrease of ceramide subclass [AP2] and an increase of ceramide subclass [NP2], sodium cholesterol sulphate and squalene (SQ) were detectable. In contrast, VIS/NIR irradiation led to an increase of ceramides [AP2] and SCS, and a decrease of SQ. These results, which are largely comparable for the different skin models investigated in vivo and ex vivo, indicate that radiation exposure in different spectral regions strongly influences radical production in skin and also results in changes in skin lipid composition, which is essential for barrier function.

Ioncopy: a novel method for calling copy number alterations in amplicon sequencing data including significance assessment.

Recently, it has been demonstrated that calling of copy number alterations (CNAs) from amplicon sequencing (AS) data is feasible. Most approaches, however, require non-tumor (germline) DNA for data normalization. Here, we present the method Ioncopy for CNA detection which requires no normal controls and includes a significance assessment for each detected alteration.Ioncopy was evaluated in a cohort of 184 clinically annotated breast carcinomas. A total number of 252 amplifications were detected, of which 183 (72.6%) could be validated by a call of an additional amplicon interrogating the same gene. Moreover, a total number of 33 deletions were found, whereof 27 (81.8%) could be validated. Analyzing the 16 most frequently amplified genes, validation rates of over 89% could be achieved for 11 of these genes. 11 of the top 16 genes showed significant overexpression in the amplified tumors. 89.5% of the HER2-amplified tumors were GRB7 and STARD3 co-amplified, whereas 68.4% of the HER2-amplified tumors had additional MED1 amplifications. Correlations between CNAs measured by amplicons in HER2 exons 19, 20 and 21 were strong (all R > 0.93). AS based detection of HER2 amplifications had a sensitivity of 90.0% and a specificity of 98.8% compared to the gold standard of HER2 immunohistochemistry combined with in situ hybridization.In summary, we developed and validated a novel method for detection and significance assessment of CNAs in amplicon sequencing data. Using Ioncopy, AS offers a straightforward and efficient approach to simultaneously analyze gene amplifications and gene deletions together with simple somatic mutations in a single assay.

Obesity in critically ill patients is associated with increased need of mechanical ventilation but not with mortality.

Worldwide incidence of obesity is increasing and impaired outcome in postoperative patients has been described. Antibiotic prescribing is complicated by different pharmacology in this population. This study evaluates mortality and morbidity of obese postoperative patients and explores possible relation to antibiotic therapy. Therefore, data obtained in a prospective study in 2009-2010 were analysed. Postoperative patients on 5 ICUs were included with >48h of ICU treatment and documented body-mass-index (BMI). Altogether 451 non-obese patients (BMI<30kg/m(2)) were compared with 130 obese patients including propensity score matching. There was significant heterogeneity of baseline characteristics. ICU-mortality was 7.5% in non-obese and 7.7% in obese patients (p>0.999), but 65.4% of obese patients required mechanical ventilation compared with only 53.2% of non-obese patients (p=0.016). These findings were validated in multivariate regression analyses (adjusted OR for ICU-mortality for obese patients 0.53, 95%-CI 0.188-1.321, p=0.197; adjusted OR for mechanical ventilation 1.841, 95%-CI 1.113-3.076, p=0.018). Results were confirmed by propensity score matching. Therapeutic drug monitoring for vancomycin (TDM) showed that underdosing and overdosing occurred more often in obese patients and sufficient TDM levels were less often achieved. In conclusion, obesity is associated with increased morbidity but ICU mortality is equal compared with a non-obese population. Pharmacological differences might explain observed differences in antibiotic therapy and in obese patients TDM might be especially of importance.

A Novel Operative Procedure for Pelvic Organ Prolapse Utilizing a MRI-Visible Mesh Implant: Safety and Outcome of Modified Laparoscopic Bilateral Sacropexy.

INTRODUCTION: Sacropexy is a generally applied treatment of prolapse, yet there are known possible complications of it. An essential need exists for better alloplastic materials. METHODS: Between April 2013 and June 2014, we performed a modified laparoscopic bilateral sacropexy (MLBS) in 10 patients using a MRI-visible PVDF mesh implant. Selected patients had prolapse POP-Q stages II-III and concomitant OAB. We studied surgery-related morbidity, anatomical and functional outcome, and mesh-visibility in MRI. Mean follow-up was 7.4 months. RESULTS: Concomitant colporrhaphy was conducted in 1/10 patients. Anatomical success was defined as POP-Q stage 0-I. Apical success rate was 100% and remained stable. A recurrent cystocele was seen in 1/10 patients during follow-up without need for intervention. Out of 6 (6/10) patients with preoperative SUI, 5/6 were healed and 1/6 persisted. De-novo SUI was seen in 1/10 patients. Complications requiring a relaparoscopy were seen in 2/10 patients. 8/10 patients with OAB were relieved postoperatively. The first in-human magnetic resonance visualization of a prolapse mesh implant was performed and showed good quality of visualization. CONCLUSION: MLBS is a feasible and safe procedure with favorable anatomical and functional outcome and good concomitant healing rates of SUI and OAB. Prospective data and larger samples are required.

Evaluation of carotenoids and reactive oxygen species in human skin after UV irradiation: a critical comparison between in vivo and ex vivo investigations.

UV irradiation is one of the most harmful exogenous factors for the human skin. In addition to the development of erythema, free radicals, that is reactive oxygen species (ROS), are induced under its influence and promote the development of oxidative stress in the skin. Several techniques are available for determining the effect of UV irradiation. Resonance Raman spectroscopy (RRS) measures the reduction of the carotenoid concentration, while electron paramagnetic resonance (EPR) spectroscopy enables the analysis of the production of free radicals. Depending on the method, the skin parameters are analysed in vivo or ex vivo. This study provides a critical comparison between in vivo and ex vivo investigations on the ROS formation and carotenoid depletion caused by UV irradiation in human skin. The oxygen content of tissue was also determined. It was shown that the antioxidant status measured in the skin samples in vivo and ex vivo was different. The depletion in the carotenoid concentration in vivo exceeded the value determined ex vivo by a factor of about 1.5, and the radical formation after UV irradiation was significantly greater in vivo by a factor of 3.5 than that measured in excised human skin, which can be explained by the lack of oxygen ex vivo.

Integration of metabolomics and expression of glycerol-3-phosphate acyltransferase (GPAM) in breast cancer-link to patient survival, hormone receptor status, and metabolic profiling.

Changes in lipid metabolism are an important but not well-characterized hallmark of cancer. On the basis of our recent findings of lipidomic changes in breast cancer, we investigated glycerol-3-phosphate acyltransferase (GPAM), a key enzyme in the lipid biosynthesis of triacylglycerols and phospholipids. GPAM protein expression was evaluated and linked to metabolomic and lipidomic profiles in a cohort of human breast carcinomas. In addition, GPAM mRNA expression was analyzed using the GeneSapiens in silico transcriptiomics database. High cytoplasmic GPAM expression was associated with hormone receptor negative status (p = 0.013). On the protein (p = 0.048) and mRNA (p = 0.001) levels, increased GPAM expression was associated with a better overall survival. Metabolomic analysis by GC-MS showed that sn-glycerol-3-phosphate, the substrate of GPAM, was elevated in breast cancer compared to normal breast tissue. LC-MS based lipidomic analysis identified significantly higher levels of phospholipids, especially phosphatidylcholines in GPAM protein positive tumors. In conclusion, our results suggest that GPAM is expressed in human breast cancer with associated changes in the cellular metabolism, in particular an increased synthesis of phospholipids, the major structural component of cellular membranes.

Long term combination treatment with bevacizumab, pegylated liposomal doxorubicin and regional abdominal hyperthermia in platinum refractory ovarian cancer: a case report and review of the literature.

BACKGROUND: Platinum resistance constitutes a therapeutic challenge in the treatment of ovarian cancer, with overall unsatisfactory response rates to standard chemotherapy and correspondingly low survival. Regional abdominal hyperthermia and bevacizumab are treatment options that have both shown the capacity to improve the results of standard chemotherapy in the platinum-resistant situation, when added to the treatment schedule. CASE REPORT: We report on a 29-year-old patient with primary platinum-refractory ovarian cancer, who was treated with a combination of pegylated liposomal doxorubicin, regional abdominal hyperthermia and bevacizumab in a four-week cycle over a long-term period of 38 months. Due to an excellent clinical and radiologic response resulting in stable disease, with a concomitant mild toxicity profile consisting only of intermitted diarrhoea and mild fatigue [corrected] , the treatment was continued in an ambulatory setting. DISCUSSION: To our knowledge we describe the first experience with combination treatment of pegylated liposomal doxorubicin with regional abdominal hyperthermia and bevacizumab in a long term setting of almost 2 years. Excellent response with comparably low toxicity was demonstrated. Further evaluation as a therapeutic option in this heavily pretreated and highly palliative patient population is warranted.