Johannes Stubert

Differentiating between malignant and benign breast masses: factors limiting sonoelastographic strain ratio.

PURPOSE We compared strain ratio vs. qualitative elastography for the further differentiation of focal breast lesions, with special focus on limiting factors. MATERIALS AND METHODS 215 patients with 224 histologically proven breast masses (116 malignant, 108 benign) were prospectively examined using a high-end ultrasound system (Philips iU22) with serial elastography function. B-mode scans and available mammograms were reviewed according to the BIRADS classification, raw elastogram data was analyzed qualitatively using the Tsukuba score and semiquantitatively by calculating the strain ratio (fat to lesion ratio). For diagnostic performance, Receiver Operating Characteristic (ROC) curve analysis was obtained. A sub-group analysis regarding breast density, lesion size, lesion depth and histological subtypes was performed. RESULTS Mean strain ratio values were 3.04 ± 0.9 for malignant and 1.91 ± 0.75 for benign lesions (p < 0,001). The areas under the ROC curve values were 0.832 (95 % CI 0.777; 0.888) for strain ratio, 0.869 (95 % CI 0.822; 0.917) for Tsukuba score, 0.822 (95 % CI 0.768; 0.876) for B-mode ultrasound and 0.853 (95 % CI 0.799; 0.907) for mammography. Sensitivity, specificity, positive predictive value and negative predictive value of the strain ratio were 90.7 %, 58.2 %, 70.3 % and 85.1 %, when a cutoff point of 2.0 was used. Only lesion depth ≤ 4 mm was associated with diagnostic failure in the multivariate analysis of factors influencing accuracy, whereas no significant correlation between breast density and lesion size and the accuracy of the strain ratio could be found. CONCLUSION The addition of strain ratio to B-mode ultrasound increases specificity without loss of sensitivity in differentiating between malignant and benign breast tumors. Strain ratio measurements should not be carried out on tumors with a lesion depth ≤ 4 mm.

A short-term follow-up of implant based breast reconstruction using a titanium-coated polypropylene mesh (TiLoop Bra)

INTRODUCTION A new approach for implant based breast reconstruction (IBBR) is the use of a titanium-coated polypropylene mesh (TCPM) as an alternative to acellular dermal matrix (ADM). This TCPM has a good biocompatibility and can be used similarly to ADM. The aim of this study is to discuss indications, limitations and complications of TCPM in IBBR. METHODS A retrospective analysis of 42 patients undergoing immediate or delayed IBBR using a TCPM was performed. Primary endpoints were incidence of infection and expander/implant with mesh removal due to infected fluid collection or extrusion. RESULTS In two patients, mild hematoma, seroma or infection occurred. Skin necrosis or capsular contraction was observed in one patient. Mesh explantation was needed in 3 cases. These events were higher among the first cases and in patients with postoperative skin infection (p = 0.003). CONCLUSION In selected patients with adequate soft tissue cover TCPM seems to be a helpful tool for implant stabilization in terms of lateral stabilization and fixation of the musculus pectoralis major. In comparison to ADM, TCPM is cheaper and initial results are promising, but further follow-up data are necessary. In patients with poor soft tissue cover ADM should be used.

Axillary lymph node dissection in early-stage invasive breast cancer: is it still standard today?

Evaluation of axillary lymph node status by sentinel lymph node biopsy (SLNB) and complete axillary lymph node dissection (ALND) are an inherent part of breast cancer treatment. Increased understanding of tumor biology has changed the prognostic and therapeutic impact of lymph node status. Non-invasive imaging techniques like axillary ultrasound, FDG-PET, or MRI revealed moderate sensitivity and high specificity in evaluation of lymph node status. Therefore, they are not sufficient for lymph node staging. Otherwise, the impact of remaining micrometastases and even macrometastases for prognosis and treatment decisions is overestimated. Considering tumor biology, the distinction of axillary metastases in isolated tumor cells (ITC, pN0(i+)); micrometastases (pN1mi), and macrometastases (pN1a) is not comprehensible. Increasing data support the thesis that remaining axillary metastases neither increase the axillary recurrence rate nor decrease overall survival. It is doubtful that axillary tumor cells are capable to complete the complex multistep metastatic process. If applied, axillary metastases are sensitive to systemic treatment and are targeted by postoperative tangential breast irradiation. Therefore, the controversy about the clinical relevance of tumor cell clusters or micrometastases in SLN is a sophisticated but not contemporary discussion. Currently, there is no indication for axillary surgery in elderly patients with favorable tumors and clinically tumor-free lymph nodes. Nonetheless, a rational and evidence-based approach to the management of clinically and sonographically N0 patients with planned breast-conserving surgery and limited tumor size is needed now.

Angiogenic factors and acute-phase proteins in serum samples of preeclampsia and HELLP patients: a matched-pair analysis

Objectives: To investigate the serum level distribution of angiogenic markers (PlGF, endoglin, sFlt-1) and acute-phase proteins (SAA, CRP) in patients with HELLP syndrome or preeclampsia (PE) including matched controls. Methods: The matching procedure revealed 46 controls for 23 HELLP cases, and 81 controls for 42 preeclamptic patients. Maternal serum concentrations were determined by immunoassays. Results: SAA and CRP levels were significantly higher in HELLP patients compared with controls. This finding was not observed in preeclamptic subgroup. Pro-angiogenic PlGF is significantly lower in PE and HELLP syndrome. Anti-angiogenic endoglin is significantly higher in PE and HELLP syndrome. The sFlt-1 analysis supports the anti-angiogenic shift in HELLP and preeclamptic patients, but with smaller differences between subgroups. The SAA/PlGF ratio showed the highest ROC value of all tested parameters in discrimination between HELLP and HELLP controls. Conclusions: These findings support the concept that patients with HELLP syndrome have both an anti-angiogenic state and a pronounced inflammatory response, while patients with PE are characterized only by an anti-angiogenic shift.

Using a titanium-coated polypropylene mesh (TiLOOP® Bra) for implant-based breast reconstruction: case report and histological analysis

In breast reconstruction (BR), autologous tissue is preferably used in patients who are not eligible for breast conserving therapy (BCT). With the improvement of surgical techniques and enhanced implant technology implantbased BR experiences new importance [1]. The invention of new materials like acellular dermal matrix (ADM) and the new titanium-coated polypropylene mesh (TCPM; TiLOOP Bra, pfm medical, Cologne, Germany) gives breast surgeons and patients new perspectives [2]. Disadvantages and difficulties of a subpectoral placement of the implant can be resolved through the use of supporting and covering materials like ADM or TCPM. These meshes provide additional cover to the skin in the lower lateral part of the breast where usually not enough muscle is available to completely cover the implant. Especially with the proven safety of skinand nipple-sparing mastectomy (SSM/NSM) and the introduction of mammography screening, immediate implant-based BR is emerging [3]. Additionally, the surgical extent and patients impairment by prosthesis reconstruction is much lower than that by autologous tissue. The use of ADM for immediate implant-based BR has been described before [4–9]. In this case, we present a patient undergoing implant-based BR using a TCPM.

Clinical differences between early- and late-onset severe preeclampsia and analysis of predictors for perinatal outcome

Abstract Aims: To analyze the clinical differences between early- and late-onset cases of severe preeclampsia and to evaluate parameters that could help to predict perinatal outcome. Methods: Over a period of 6 years, all cases of severe preeclampsia (n=68) at our institution were included in a retrospective cohort analysis. Differences between early (<34 weeks, n=44) and late (≥34 weeks, n=24) onset of the disease were evaluated. Risk factors for low 5-min Apgar score (≤7), small-for-gestational-age (SGA) infants and neonatal acidosis (umbilical arterial pH <7.20) were identified and considered in a multiple logistic regression model. Results: Early- and late-onset severe preeclampsia differed from each other remarkably. Perinatal outcome was unfavorable in early-onset disease and seemed to be mainly a result of premature delivery and development of fetal growth restriction. Abnormal uterine Doppler velocimetry increased the risk of low 5-min Apgar values [odds ratio (OR) 8.0, P=0.012] and preterm birth <34+0 weeks (OR 17.9, P<0.001). An increased resistance of the umbilical artery was associated with a higher risk for SGA birth weight (OR 4.9, P=0.010). Conclusion: Preeclampsia is a heterogeneous syndrome even if only severe cases were analyzed. Abnormal Doppler flow characteristics facilitated the identification of patients who were at increased risk for worse perinatal outcome.

Isoflavones – Mechanism of Action and Impact on Breast Cancer Risk

Isoflavones are plant-derived substances with weak estrogenic effects. Asian populations are high consumers of soy products which are rich in isoflavones. The lower breast cancer incidence in Asian women compared with Western women has been associated with the possibility of a preventive isoflavone effect on cancer risk. The aim of this review is to give an overview of current research data on the influence of isoflavones on the risk of primary breast cancer development as well as the risk of recurrence in breast cancer patients. Despite inconsistencies in the available data, an inverse correlation between isoflavone intake and risk of breast cancer is likely. However, a negative impact on breast cancer disease, especially on hormone receptor-positive tumors, cannot be excluded at present.

Biocompatibility, cell growth and clinical relevance of synthetic meshes and biological matrixes for internal support in implant-based breast reconstruction

PurposeBiological matrixes and synthetic meshes are increasingly used in implant-based breast reconstruction (IBBR). The objective was to test different materials used for internal support in IBBR in regards to biocompatibility and discuss possible limitations in a clinical context.Materials and methodsIn vitro investigations were performed on four relevant cell lines: Normal Human Dermal Fibroblasts (NHDF), Human White Preadipocytes (HWP), Endothelial cells (HDMEC) and Skeletal muscle cells (SkMC). A titanium-coated polypropylene mesh (TiLOOP® Bra), a partially resorbable mesh (SERAGYN BR®) and a porcine derived biologic matrix (Strattice™) were investigated. Test of cytotoxicity, cell proliferation and oxidative stress was performed. Real-time cell analysis was used to determine adhesion rate. Light- and scanning electron microscopy investigated cell migration.ResultsNo relevant cytotoxicity was detected for any mesh or matrix. Good cell proliferation was observed in all materials with best results for NHDF and SkMC. For HWP and HDMEC decreased proliferation and adherence to the synthetic meshes and biologic matrix were observed. Real-time cell analysis of fibroblasts incubated with the corresponding material, showed increased impedance for the synthetic meshes. A morphologic cell change was observed within all materials. Scanning electron microscopy showed good cell penetration into the meshes and matrix. The material compositions did not seem to influence the clinical outcome, although the biological matrix was much thicker compared to the synthetic meshes.ConclusionBiochemical examination showed good biocompatibility for the investigated meshes and matrix. All products seem to have their value in IBBR and can be recommended for IBBR.

Medical Prevention of Breast Cancer

Breast cancer is the most common cancer of women in Western Europe and North America. Effective strategies of medical prevention could reduce the burden of breast cancer mortality. The best evidence for a risk reduction exists for hormonal agents such as tamoxifen and raloxifene (22-72%) or aromatase inhibitors (50-65%). However, the severity of side effects and the lack of evidence for an improved survival compromise the risk/benefit balance. In this review the results of chemoprevention studies, including new treatment approaches, are summarized with critical discussion of their use in clinical practice.

miRNA expression profiles determined in maternal sera of patients with HELLP syndrome

Objective: Syndrome of hemolysis, elevated liver enzymes and low platelets (HELLP) represents a distinct subgroup of severe preeclampsia. The aim of our study was to identify differentially expressed miRNAs in sera of patients with HELLP syndrome in comparison to unaffected controls. Study design: Blood samples were obtained from patients with manifest HELLP syndrome and matched unaffected controls. The expression of 754 mature miRNAs was assessed using the TaqMan Array format (n = 12). Results of seven differentially expressed miRNAs were further validated by single quantitative real-time polymerase chain reaction (qPCR) assays. Results: Serum miRNA analysis allowed detection of maternal and fetal miRNAs. Distinct miRNA expressions were confirmed for miR-122, miR-758 and miR-133a represented by a median up-regulation ≥two-fold in the HELLP group. The liver specific miR-122 was 11.5-fold increased with an area under curve (AUC) of 0.82 in the receiver operating characteristic (ROC) analysis. Cluster analyses of our data uncovered subgroups of HELLP patients were associated with clinical subtypes and differences in organ manifestation. Conclusion: In our proof of principle study, we demonstrated that patients with HELLP syndrome showed alterations of serum miRNA expression patterns. Data analysis goes along with the hypothesis that HELLP syndrome is regarded to be a heterogeneous disease.