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Purpose: Members of the Bcl-2 family act as master regulators of mitochondrial homeostasis and apoptosis. We analyzed whether ERBB2 influences the prognosis of breast cancer by influencing the proapoptotic versus antiapoptotic balance of Bcl-2 family members.Experimental Design: ERBB2-regulated Bcl-2 family members were identified by inducible expression of ERBB2 in MCF-7 breast cancer cells and by correlation analysis with ERBB2 expression in breast carcinomas. The prognostic relevance of ERBB2-regulated and all additional Bcl-2 family members was determined in 782 patients with untreated node-negative breast cancer. The biological relevance of ERBB2-induced inhibition of apoptosis was validated in a murine tumor model allowing conditional ERBB2 expression.Results: ERBB2 caused an antiapoptotic phenotype by upregulation of MCL-1, TEGT, BAG1, BNIP1, and BECN1 as well as downregulation of BAX, BMF, BNIPL, CLU, and BCL2L13. Upregulation of the antiapoptotic MCL-1 [P = 0.001, hazard ratio (HR) 1.5] and BNIP3 (P = 0.024; HR, 1.4) was associated with worse prognosis considering metastasis-free interval, whereas clusterin (P = 0.008; HR, 0.88) and the proapoptotic BCL2L13 (P = 0.019; HR, 0.45) were associated with better prognosis. This indicates that ERBB2 alters the expression of Bcl-2 family members in a way that leads to adverse prognosis. Analysis of apoptosis and tumor remission in a murine tumor model confirmed that the prototypic Bcl-2 family member Bcl-xL could partially substitute for ERBB2 to antagonize tumor remission.Conclusions: Our results support the concept that ERBB2 influences the expression of Bcl-2 family members to induce an antiapoptotic phenotype. Antagonization of antiapoptotic Bcl-2 family members might improve breast cancer therapy, whereby MCL-1 and BNIP3 represent promising targets. Clin Cancer Res; 16(2); 451–60

Purpose: According to current guidelines, molecular tests predicting the outcome of breast cancer patients can be used to assist in making treatment decisions after consideration of conventional markers. We developed and validated a gene expression signature predicting the likelihood of distant recurrence in patients with estrogen receptor (ER)–positive, HER2-negative breast cancer treated with adjuvant endocrine therapy.Experimental Design: RNA levels assessed by quantitative reverse transcriptase PCR in formalin-fixed, paraffin-embedded tumor tissue were used to calculate a risk score (Endopredict, EP) consisting of eight cancer-related and three reference genes. EP was combined with nodal status and tumor size into a comprehensive risk score, EPclin. Both prespecified risk scores including cutoff values to determine a risk group for each patient (low and high) were validated independently in patients from two large randomized phase III trials [Austrian Breast and Colorectal Cancer Study Group (ABCSG)-6: n = 378, ABCSG-8: n = 1,324].Results: In both validation cohorts, continuous EP was an independent predictor of distant recurrence in multivariate analysis (ABCSG-6: P = 0.010, ABCSG-8: P < 0.001). Combining Adjuvant!Online, quantitative ER, Ki67, and treatment with EP yielded a prognostic power significantly superior to the clinicopathologic factors alone [c-indices: 0.764 vs. 0.750, P = 0.024 (ABCSG-6) and 0.726 vs. 0.701, P = 0.003 (ABCSG-8)]. EPclin had c-indices of 0.788 and 0.732 and resulted in 10-year distant recurrence rates of 4% and 4% in EPclin low-risk and 28% and 22% in EPclin high-risk patients in ABCSG-6 (P < 0.001) and ABCSG-8 (P < 0.001), respectively.Conclusions: The multigene EP risk score provided additional prognostic information to the risk of distant recurrence of breast cancer patients, independent from clinicopathologic parameters. The EPclin score outperformed all conventional clinicopathologic risk factors. Clin Cancer Res; 17(18); 6012–20. ©2011 AACR.

Supplementary Table 4 from The Humoral Immune System Has a Key Prognostic Impact in Node-Negative Breast Cancer

Supplementary Table 2 from The Humoral Immune System Has a Key Prognostic Impact in Node-Negative Breast Cancer

Supplementary Tables 1, 3, 5-6, Figures 1-6 from The Humoral Immune System Has a Key Prognostic Impact in Node-Negative Breast Cancer

Estrogen receptor (ER) expression and proliferative activity are established prognostic factors in breast cancer. In a search for additional prognostic motifs, we analyzed the gene expression patterns of 200 tumors of patients who were not treated by systemic therapy after surgery using a discovery approach. After performing hierarchical cluster analysis, we identified coregulated genes related to the biological process of proliferation, steroid hormone receptor expression, as well as B-cell and T-cell infiltration. We calculated metagenes as a surrogate for all genes contained within a particular cluster and visualized the relative expression in relation to time to metastasis with principal component analysis. Distinct patterns led to the hypothesis of a prognostic role of the immune system in tumors with high expression of proliferation-associated genes. In multivariate Cox regression analysis, the proliferation metagene showed a significant association with metastasis-free survival of the whole discovery cohort [hazard ratio (HR), 2.20; 95% confidence interval (95% CI), 1.40–3.46]. The B-cell metagene showed additional independent prognostic information in carcinomas with high proliferative activity (HR, 0.66; 95% CI, 0.46–0.97). A prognostic influence of the B-cell metagene was independently confirmed by multivariate analysis in a first validation cohort enriched for high-grade tumors (n = 286; HR, 0.78; 95% CI, 0.62–0.98) and a second validation cohort enriched for younger patients (n = 302; HR, 0.83; 95% CI, 0.7–0.97). Thus, we could show in three cohorts of untreated, node-negative breast cancer patients that the humoral immune system plays a pivotal role in metastasis-free survival of carcinomas of the breast. [Cancer Res 2008;68(13):5405–13]

Background: Some countries have implemented stand-alone human papillomavirus (HPV) testing while others consider cotesting for cervical cancer screening. We compared both strategies within a population-based study. Methods: The MARZY cohort study was conducted in Germany. Randomly selected women from population registries aged ≥30 years (n = 5,275) were invited to screening with Pap smear, liquid-based cytology (LBC, ThinPrep), and HPV testing (Hybrid Capture2, HC2). Screen-positive participants [ASC-US+ or high-risk HC2 (hrHC2)] and a random 5% sample of screen-negatives were referred to colposcopy. Post hoc HPV genotyping was conducted by GP5+/6+ PCR-EIA with reverse line blotting. Sensitivity, specificity (adjusted for verification bias), and potential harms, including number of colposcopies needed to detect 1 precancerous lesion (NNC), were calculated. Results: In 2,627 screened women, cytological sensitivities (Pap, LBC: 47%) were lower than HC2 (95%) and PCR (79%) for CIN2+. Cotesting demonstrated higher sensitivities (HC2 cotesting: 99%; PCR cotesting: 84%), but at the cost of lower specificities (92%–95%) compared with HPV stand-alone (HC2: 95%; PCR: 94%) and cytology (97% or 99%). Cotesting versus HPV stand-alone showed equivalent relative sensitivity [HC2: 1.06, 95% confidence interval (CI), 1.00–1.21; PCR: 1.07, 95% CI, 1.00–1.27]. Relative specificity of Pap cotesting with either HPV test was inferior to stand-alone HPV. LBC cotesting demonstrated equivalent specificity (both tests: 0.99, 95% CI, 0.99–1.00). NNC was highest for Pap cotesting. Conclusions: Cotesting offers no benefit in detection over stand-alone HPV testing, resulting in more false positive results and colposcopy referrals. Impact: HPV stand-alone screening offers a better balance of benefits and harms than cotesting. See related commentary by Wentzensen and Clarke, p. 432

Introduction Advanced gynecologic cancers have a poor prognosis and constitute a major challenge for adequate treatment strategies. By analyzing and targeting molecular alterations, molecular guided treatments may be a viable option for the treatment of advanced gynecologic cancers. Patients and Methods In this single‐center, real‐world retrospective analysis of our platform for precision cancer medicine (PCM), we describe the molecular profiling of 72 patients diagnosed with different types of advanced gynecologic malignancies. Tumor samples of the patients were examined by next‐generation sequencing panel and immunohistochemistry (IHC). Results In total, we identified 209 genetic aberrations in 72 patients. The ten most frequent alterations were TP53 (n = 42, 20%), KRAS (n = 14, 6.6%), PIK3CA (n = 11, 5.2%), PIK3R1 (n = 9, 4.3%), ATR (n = 8, 3.8%), PTEN (n = 8, 3.8%), BRCA1 (n = 6, 2.8%), NF1 (n = 4, 1.9%), NOTCH1 (n = 4, 1.9%), and POLE (n = 4, 1.9%), which account for more than half of all molecular alterations (52.6%). In 21 (29.1%) patients only one mutation could be detected, and 44 (61.1%) patients had more than one mutation. No molecular alterations were detected in seven (9.7%) patients. IHC detected expression of phosphorylated mammalian target of rapamycin and epidermal growth factor receptor in 58 (80.6%) and 53 (73.6%) patients, respectively. In over two thirds (n = 49, 68.1%), a targeted therapy was suggested, based on the identified genetic aberrations. The most frequently recommended specific treatment was the combination of everolimus with exemestane (n = 18, 25 %). Conclusion Based on our observations, it seems that PCM might be a feasible approach for advanced gynecologic cancers with limited treatment options. Implications for Practice Nowadays molecular profiling of advanced gynecologic malignancies is feasible in the clinical routine. A molecular portrait should be done for every patient with an advanced therapy‐refractory gynecologic malignancy to offer molecular‐based treatment concepts., To determine the feasibility of precision cancer medicine (PCM) in gynecologic cancers, this retrospective study analyzed patients with advanced gynecologic cancers enrolled and profiled in a PCM platform, MONDTI, focusing on the technical feasibility to map the molecular profiles of advanced, pretreated, and mainly relapsed gynecologic cancers and to subsequently target the detected molecular alterations

Background The purpose of this systematic review update and meta-analysis was to analyze resistance exercise (RE) intervention trials in breast cancer survivors (BCS) regarding their effect on breast cancer-related lymphedema (BCRL) status and upper and lower extremity strength. Methods Systematic literature search was conducted utilizing PubMed, MEDLINE, and Embase databases. Any exercise intervention studies—both randomized controlled and uncontrolled—which assessed the effects of RE on BCRL in BCS in at least one intervention group published between 1966 and 31st January 2020 were included. Included articles were analyzed regarding their level of evidence and their methodological quality using respective tools for randomized and nonrandomized trials of the Cochrane collaboration. Meta-analysis for bioimpedance spectroscopy (BIS) values as well as upper and lower extremity strength was conducted. Results Altogether, 29 studies were included in the systematic review. Results of six studies with altogether twelve RE intervention groups could be pooled for meta-analysis of the BCRL. A significant reduction of BCRL after RE was seen in BIS values (95% CI − 1.10 [− 2.19, − 0.01] L-Dex score). Furthermore, strength results of six studies could be pooled and meta-analysis showed significant improvements of muscular strength in the upper and lower extremities (95% CI 8.96 [3.42, 14.51] kg and 95% CI 23.42 [11.95, 34.88] kg, respectively). Conclusion RE does not have a systematic negative effect on BCRL and, on the contrary, potentially decreases it.

The aim of this prospective randomized, double-masked, placebo-controlled, multicenter study was to analyze the surgeon’s individual assessment of tissue quality during pelvic floor surgery in postmenopausal women pre-treated with local estrogen therapy (LET) or placebo cream. Secondary outcomes included intraoperative and early postoperative course of the two study groups. Surgeons, blinded to patient’s preoperative treatment, completed an 8-item questionnaire after each prolapse surgery to assess tissue quality as well as surgical conditions. Our hypothesis was that there is no significant difference in individual surgical assessment of tissue quality between local estrogen or placebo pre-treatment. Multivariate logistic regression analysis was performed to identify independent risk factors for intra- or early postoperative complications. Out of 120 randomized women, 103 (86%) remained for final analysis. Surgeons assessed the tissue quality similarity in cases with or without LET, representing no statistically significant differences concerning tissue perfusion, tissue atrophy, tissue consistency, difficulty of dissection and regular pelvic anatomy. Regarding pre-treatment, the rating of the surgeon correlated significantly with LET (r = 0.043), meaning a correct assumption of the surgeon. Operative time, intraoperative blood loss, occurrence of intraoperative complications, total length of stay, frequent use of analgesics and rate of readmission did not significantly differ between LET and placebo pre-treatment. The rate of defined postoperative complications and use of antibiotics was significantly more frequent in patients without LET (p = 0.045 and p = 0.003). Tissue quality was similarly assessed in cases with or without local estrogen pre-treatment, but it seems that LET prior to prolapse surgery may improve vaginal health as well as tissue-healing processes, protecting these patients from early postoperative complications.

ZusammenfassungDie Implantation spannungsfreier Bänder („tension free vaginal tape“ [TVT]) ist eine minimalinvasive Technik zur Behandlung der Belastungsinkontinenz. Um den Stellenwert und die Besonderheiten der Methode bei älteren Menschen zu evaluieren, wurde eine selektive Literaturrecherche in PubMed mit den Stichworten „urinary incontinence“/„tension free vaginal tape“/„stress incontinence“ AND „elderly“ durchgeführt. Angesichts der demografischen Entwicklung weltweit erweist sich die Harninkontinenz im Alter als zunehmendes medizinisches und sozioökonomisches Problem. Ein TVT kann selbst bei Hochaltrigen unter folgenden Bedingungen ins Auge gefasst werden: grundsätzlich fehlende Kontraindikation gegen einen chirurgischen Eingriff; Vorliegen einer Belastungs- oder Mischinkontinenz (mit hohem Belastungsanteil); Versagen der konservativen Therapie. Unter der Voraussetzung von Operationswunsch und gegebener Operabilität zeigen die Langzeitergebnisse des TVT über 11 Jahre eine persistierende Kontinenzrate von mehr als 80 %. Die Operation ist sicher und effektiv, geht allerdings mit einer erhöhten Rate von postoperativen Harnwegsinfekten und De-Novo-Dranginkontinenz einher.

// Gerald W. Prager 1, 8 , Matthias Unseld 1, 8 , Fredrik Waneck 3, 8 , Robert Mader 1, 8 , Fritz Wrba 2, 8 , Markus Raderer 1, 8 , Thorsten Fuereder 1, 8 , Phillip Staber 4, 8 , Ulrich Jager 4, 8 , Markus Kieler 1, 8 , Daniela Bianconi 1, 8 , Mir Alireza Hoda 7, 8 , Lukas Baumann 9 , Alexander Reinthaller 5, 8 , Walter Berger 6, 8 , Christoph Grimm 5, 8 , Heinz Kolbl 5, 8 , Maria Sibilia 6, 8 , Leonhard Mullauer 2, 8 and Christoph Zielinski 1, 8 1 Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria 2 Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria 3 Department of Interventional Radiology, Medical University of Vienna, Vienna, Austria 4 Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria 5 Department of General Gynecology and Gynecological Oncology, Medical University of Vienna, Vienna, Austria 6 Department of Medicine I, Institute of Cancer Research, Medical University of Vienna, Vienna, Austria 7 Department of Surgery, Institute of Cancer Research, Medical University of Vienna, Vienna, Austria 8 Comprehensive Cancer Center of the Medical University of Vienna, Vienna, Austria 9 Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria Correspondence to: Gerald W. Prager, email: gerald.prager@meduniwien.ac.at Keywords: precision medicine; molecular profile Received: May 28, 2018 Accepted: January 02, 2019 Published: January 29, 2019 ABSTRACT Background: The concept of personalized medicine defines a promising approach in cancer care. High-throughput genomic profiling of tumor specimens allows the identification of actionable mutations that potentially lead to tailored treatment for individuals’ benefit. The aim of this study was to prove efficacy of a personalized treatment option in solid tumor patients after failure of standard treatment concepts. Results: Final analysis demonstrates that 34 patients (62%) had a longer PFS upon experimental treatment (PFS1) when compared to previous therapy (PFS0); PFS ratio > 1.0 ( p = 0.002). The median PFS under targeted therapy based on molecular profiling (PFS1) was 112 days (quartiles 66/201) and PFS0 = 61 days (quartiles 51/92; p = 0.002). Of the 55 patients, 31 (56%) showed disease control (DCR), consisting of 2 (4%) patients which achieved a complete remission, 14 (25%) patients with a partial remission and 15 (27%) patients who had a stabilization of disease. Median OS from start of experimental therapy was 348 days (quartiles 177/664). Conclusion: The prospective trial EXACT suggests that treatment based on real-time molecular tumor profiling leads to superior clinical benefit. Materials and Methods: In this prospective clinical phase II trial, 55 cancer patients, after failure of standard treatment options, aimed to achieve a longer progression-free survival on the experimental treatment based on the individual’s molecular profile (PFS1) when compared to the last treatment given before (PFS0). The personalized medicine approach was conceived to be clinical beneficial for patients who show a PFS ratio (PFS 1/PFS0) of > 1.0.

Purpose On January 1st, 2018, the ÖGZ (Austrian Society of Cytology) revised its cytological nomenclature to make it more similar to the 2015 Bethesda system. Following these changes, the Austrian Society of Gynecology and Obstetrics felt it necessary to revise the approach currently used in Austria to diagnose and treat CIN and to review the procedures to be followed when the quality of cytological specimens is unsatisfactory. It was not possible to adopt the German S3 guideline “Prevention of Cervical Cancer” in its entirety, because the Munich III gynecological cytology nomenclature used in Germany is not used in Austria. This made it necessary to compile a separate scientific opinion for Austria. Methodology The OEGGG worked together with the ÖGZ (Austrian Society for Cytology), AGO Austria (Austrian Working Group for Gynecological Oncology), the AGK (Colposcopy Working Group), and physicians representing gynecologists in private practice. The different scientific associations nominated representatives, who attended the various meetings. After an in-depth analysis of the recent literature, three meetings and numerous votes by telephone, we were able to achieve a consensus about the contents of this guideline. Recommendations The guideline provides recommendations for the diagnosis and treatment of CIN which take account of the gynecological cytology nomenclature used in Austria.

The COVID-19 pandemic led to dramatical changes in elective medical care. We analysed its impact on patients with female pelvic floor dysfunction during the 6 weeks of lockdown in Austria. A cross-sectional study was conducted: All 99 women who presented at the urogynaecologic outpatient clinic of the Medical University of Vienna with pelvic organ prolapse (POP) or urinary incontinence (UI) from December 2019 up to the lockdown in March 2020 were included and contacted. 97% of these women (96 participants) agreed to participate in the survey conducted to asses pelvic floor related quality of life (QoL) through telephone- interrogation. The mean age was 59 ± 14.8 years, the POP group consisted of 42 women while the UI group included 54 women. Most participants (83% of POP and 81% of UI cases) stated that their female pelvic floor dysfunction had remained equally relevant or had become even more significant during the lockdown. Associated symptoms and psychological strain also maintained their relevance during the lockdown (UI: p = 0.229, POP: p = 0.234). Furthermore, 97% of all interviewed women indicated to be strongly willing to continue their treatment. A generalised linear model regression revealed no clinical or demographic risk factors for psychological strain during the lockdown (p &gt, 0.05). Our results demonstrate that women’s QoL remains significantly impaired by their pelvic-floor disorders even during a worldwide crisis such as COVID-19. Therefore, elective disciplines such as urogynaecology urgently require novel and innovative strategies for continued patient care even in times of a lockdown.

Background: The aim of this study was to identify clinical risk factors for increased post-void residual (PVR) volumes in patients undergoing vaginal prolapse surgery and to find out whether uterus preservation or prolapse hysterectomy influences the incidence of postoperative urinary retention. Methods: This retrospective study included women who presented with pelvic organ prolapse (POP) and planned prolapse surgery between January 2017 and July 2019. PVR was assessed postoperatively and increased amounts were defined as incomplete voiding with residual urine volume greater than 150 mL. Results: Increased PVR at the first postoperative day occurred in 31.8% (56/176). Body mass index (BMI) was significantly lower in patients with increased PVR after pelvic floor surgery compared to patients with normal PVR amounts (p = 0.040). Furthermore, during multiple logistic regression analysis, low BMI (p = 0.009) as well as prolapse hysterectomy (p = 0.032) turned out to be the strongest risk factors associated with increased PVR volume. Conclusion: This is the first study identifying prolapse hysterectomy as an independent risk factor for increased PVR after surgical prolapse repair. Our results might be helpful in counseling patients prior to surgery and underline the option of uterus preservation during prolapse surgery in selected cases.

Benigne sowie maligne Raumforderungen der Adnexe konnen die Indikation fur eine Adnexektomie sein. Es sind zwei Zugangswege zur Adnexe moglich, uber eine Laparoskopie oder uber eine Laparotomie, das Vorgehen wird individuell festgelegt. Die operativen und anasthesiologischen Besonderheiten werden in diesem Kapitel vorgestellt.

Die plastische und rekonstruktive Mammachirugie umfasst Augmentations- sowie Reduktionsplastiken und die chirurgische Rekonstruktion nach Mastektomie. Die unterschiedlichen Operationsverfahren werden zusammen mit dem anasthesiologischen Management in diesem Kapitel beschrieben.

Es gibt zwei Indikationen in der Geburtshilfe, die ein operatives Eingreifen rechtfertigen: Gefahr fur die Mutter und Gefahr fur das Kind. Um eine vaginal operative Geburt vornehmen zu konnen, muss der Muttermund vollstandig eroffnet, die Fruchtblase bereits gesprungen sein und der kindliche Kopf sich mindestens in Beckenmitte befinden. Die Vakuumextraktion ist die haufigste vaginal-operative Entbindungsmethode. Das anasthesiologische Management entspricht dem der vaginalen Geburt.

The decades-long global obesity epidemic has resulted in steady increase in the incidence of obesity-related malignancies. The associated diagnostic and therapeutic implications present a clinical challenge for gynecologic oncology treatment strategies. Recent studies have provided solid evidence for an independent, linear, positive correlation between a pathologically increased body mass index and the probability of developing endometrial or postmenopausal breast cancer. The pathogenesis is complex and the subject of current research. Proposed causes include pathologically increased serum levels of sexual steroids and adiponectin, obesity-induced insulin resistance, and systemic inflammatory processes. The scientific evidence for an association between obesity and other gynecological malignancies is, however, less solid. The clinical relevance of obesity as a risk factor for epithelial ovarian cancer, cervical cancer and vulvar cancer appears to be negligible. Nevertheless, obesity appears to have a negative impact on prognosis and oncologic outcomes for all gynecological cancers. Whether or not this effect can be interpreted as correlative or causal is still a subject of ongoing debate.

Objective Aim of the study was to investigate the expression of transforming growth factor-β1 (TGF-β1), a key regulator of the extracellular matrix composition, in the uterosacral ligaments (USLs) of women with pelvic organ prolapse (POP) compared with controls. We hypothesized that the expression pattern of TGF-β1 differs between postmenopausal women with or without POP. Methods Under ethical approval, USL samples were obtained from postmenopausal women undergoing vaginal hysterectomy for stage two or greater pelvic organ prolapse (cases, n = 70) and from postmenopausal women without pelvic organ prolapse undergoing vaginal hysterectomy for benign indications (controls, n = 30). Immunohistochemical staining was performed from paraffin embedded tissue using anti-TGF-β1 antibodies. The expression of TGF-β1 was evaluated by the pathologist, who was blinded to all clinical data. Results The expression of TGF-s1 was similar in patients with symptomatic POP (89 % positive) and in controls (90 % positive) without any signs of prolapse (p = 0.091). Age-adjusted analysis did not significantly alter these results. Regarding POP-Q stages, TGF-s1 was significantly more frequently expressed in severe prolapse cases compared to moderate/mild cases (POP-Q stage IV versus POP-Q stage II and III; p = 0.001). No significant association could be detected between TGF-s1 expression and age, BMI and parity in cases with POP (p > 0.05). As published previously, advanced patients’ age as well as early menopausal age remained independent risk factors associated with POP in multiple logistic regression analysis (p = 0.001; p = 0.02). Conclusion Although our study detected POP-Q stage related alterations in USL composition and TGF-s1 expression, there was no significant difference in the expression of TGF-β1 in cases with or without prolapse.

Precision medicine for breast cancer relies on biomarkers to select therapies. However, the reliability of biomarkers drawn from gene expression arrays has been questioned and calls for reassessment, in particular for large datasets. We revisit widely used data-normalization procedures and evaluate differences in outcome in order to pinpoint the most reliable reprocessing methods biomarkers can be based upon. We generated a database of 3753 breast cancer patients out of 38 studies by downloading and curating patient samples from NCBI-GEO. As gene-expression biomarkers, we select the assessment of receptor status and breast cancer subtype classification. Each normalization procedure is applied separately, and biomarkers are then evaluated for each patient. Differences between normalization pipelines are quantified as percentages of patients having outcomes different for each pipeline. Some normalization procedures lead to quite consistent biomarkers, differing only in 1-2% of patients. Other normalization procedures—some of them have been used in many clinical studies—end up with distrusting discrepancies (10% and more). A good deal of doubt regarding the reliability of microarrays may root in the haphazard application of inadequate preprocessing pipelines. Several modes of batch corrections are evaluated regarding a possible improvement of receptor prediction from gene expression versus the golden standard of immunohistochemistry. Finally, we nominate those normalization methods yielding consistent and trustable results. Adequate bioinformatics data preprocessing is key and crucial for any subsequent statistics to arrive at trustable results. We conclude with a suggestion for future bioinformatics development to further increase the reliability of cancer biomarkers.

Lung cancer during pregnancy represents a rare disease. In this case report, we present a patient at advanced and metastasized stage of signet ring cell carcinoma who presented in the22ndweek of gestation.

Aim: To evaluate pre-treatment serum C-reactive protein (CRP) level as a prognostic parameter in patients with adenocarcinoma of the uterine cervix. Materials and Methods: Pre-treatment CRP levels were analyzed to determine potential associations with clinicopathological parameters and to assess prognostic value in 46 patients with sole adenocarcinoma of the uterine cervix. Results: The mean (±SD) pre-treatment serum CRP level was 5.82 (7.21) mg/l. Serum CRP concentration significantly correlated positively with age at diagnosis (p=0.001), lymphovascular space invasion (p=0.0026), recurrent disease (p=0.0001) and International Federation of Gynecology and Obstetrics (FIGO) stage (p=0.0002). In multivariate Cox regression models with age, FIGO stage, histological grade and lymph node status, elevated CRP and cancer antigen 125 levels were associated with shortened survival (p

The modern sling procedures for treating female stress urinary incontinence encompass numerous methods, materials and manufacturers. On the basis of the current S2e guidelines, the methods used most frequently in the diagnosis of and therapy for stress urinary incontinence in women are critically illustrated. An individualised procedure is necessary for the choice of the surgical method, especially in the presence of accompanying pathologies. This article is intended to help the treating physician to carry out quality-assured diagnostics and therapy for the patient and to offer the best possible urogynaecological management. In addition to the complications and chances of success of the surgical options, the legal aspects of therapy planning are also taken into consideration.Die modernen Schlingenverfahren zur Behandlung der weiblichen Belastungsinkontinenz variieren heute zwischen zahlreichen Verfahren, Materialien und Herstellern. Basierend auf der aktuellen S2e-Leitlinie werden die am häufigsten angewendeten Verfahren bei der Diagnostik und Therapie der Belastungsinkontinenz der Frau kritisch beleuchtet. Bei der Wahl der Operationsmethode ist ein individualisiertes Vorgehen erforderlich, insbesondere, wenn Begleitpathologien vorliegen. Der Beitrag soll den behandelnden Ärzten helfen, die Diagnostik und Therapie der Patientinnen qualitätsgesichert durchzuführen und die bestmögliche urogynäkologische Versorgung anbieten zu können. Dabei werden neben den Komplikationen und Erfolgsaussichten der operativen Möglichkeiten auch juristische Aspekte bei der Therapieplanung berücksichtigt.

Lymph node ratio (LNR) can predict treatment outcome and prognosis in patients with solid tumors. Aim of the present analysis was to confirm the concept of using LNR for assessing outcome in patients with vulvar cancer after surgery with inguinal lymphadenectomy in a large multicenter project.The AGO-CaRE-1 study multicenter database was used for analysis. LNR was defined as ratio of number of positive lymph nodes (LN) to the number of resected. Previously established LNR risk groups were used to stratify patients. LNR was investigated with respect to clinical parameters. Univariate and multivariable survival analyses were performed to assess the value of LNR in order to predict overall (OS) and progression-free (PFS) survival.In total, 1047 patients treated with surgery including inguinal lymph node resection for squamous cell carcinoma of the vulva were identified from the database. Of these, 370 (35.3%) were found to have positive inguinal LN. In total, 677 (64.7%) had a LNR of 0% (N0), 255 (24.4%) a LNR of0% 20%, and 115 (11%) a LNR of ≥20%. Patients with higher LNR were found to have larger tumor size (P .001), advanced tumor stage (P .001), high tumor grade (P .001), and deep stromal invasion (P .001), more frequently. Three-year PFS rates were 75.7%, 44.2%, and 23.1% and three-year OS rates were 89.7%, 65.4%, and 41.9%, in patients with LNRs 0%,0% 20%, and ≥20%, respectively (P .001, P .001). On multivariable analyses LNR (HR 7.75, 95%-CI 4.01-14.98, P .001), FIGO stage (HR 1.41, 95%-CI 1.18-1.69, P .001), and patient's performance status (HR 1.59, 95%-CI 1.39-1.82, P .001), were associated with PFS. In addition, LNR (HR 12.74, 95%-CI 5.64-28.78, P .001), and performance status (HR 1.72, 95%-CI 1.44-2.07, P .001) were also the only two parameters independently associated with OS. LNR generally showed stronger correlation than number of affected LN when comparing the two different multivariable models.In women with vulvar cancer LNR appears to be a consistent, independent prognostic parameter for both PFS and OS and allows patient stratification into three distinct risk groups. In survival analyses, LNR outperformed nodal status and number of positive nodes.

The working group recommends against contralateral prophylactic mastectomy (CPM) in women with breast cancer without a family history or genetic predisposition with unilateral breast cancer. This is based on the low risk of developing contralateral breast cancer, the lack of a survival benefit, the increased risk of surgical complications, and the lack of benefit on quality of life.

Purpose Therapeutic decisions in breast cancer patients crucially depend on the status of estrogen receptor, progesterone receptor and HER2, obtained by immunohistochemistry (IHC). These are known to be inaccurate sometimes, and we demonstrate how to use gene-expression to increase precision of receptor status. Methods We downloaded data from 3241 breast cancer patients out of 36 clinical studies. For each receptor, we modelled the mRNA expression of the receptor gene and a co-gene by logistic regression. For each patient, predictions from logistic regression were merged with information from IHC on a probabilistic basis to arrive at a fused prediction result. Results We introduce Sankey diagrams to visualize the step by step increase of precision as information is added from gene expression: IHC-estimates are qualified as ‘confirmed’, ‘rejected’ or ‘corrected’. Additionally, we introduce the category ‘inconclusive’ to spot those patients in need for additional assessments so as to increase diagnostic precision and safety. Conclusions We demonstrate a sound mathematical basis for the fusion of information, even if partly contradictive. The concept is extendable to more than three sources of information, as particularly important for OMICS data. The overall number of undecidable cases is reduced as well as those assessed falsely. We outline how decision rules may be extended to also weigh consequences, being different in severity for false-positive and false-negative assessments, respectively. The possible benefit is demonstrated by comparing the disease free survival between patients whose IHC could be confirmed versus those for which it was corrected. Electronic supplementary material The online version of this article (10.1007/s10549-018-4920-x) contains supplementary material, which is available to authorized users.