Introitussonographie in der Diagnostik der Streßharninkontinenz : Langzeitergebnisse der Kolposuspension nach Burch und der Kolporrhaphia anterior in der operativen Therapie der weiblichen Streßharninkontinenz

Die Harninkontinenz zählt zu den häufigsten Erkrankungen der Frau, mit der der Gynäkologe immer häufiger konfrontiert wird. Die richtige Diagnose und Therapie ist entscheidend für eine rasche Behebung der Einschränkung der Lebensqualität der Patientin. Die gestörte Beckenbodenmorphologie streßinkontinenter Patientinnen lässt sich mittels Introitussonographie mit geringem technischen Aufwand darstellen. Dabei kann die Position des Blasenhalses ebenso wie die Form und Lage der Urethra in Ruhe und unter Belastung sowohl in Einzelbildern als auch in dynamischen Bildsequenzen bestimmt werden. 1. Fragestellung: In der vorgelegten Arbeit wurden die Langzeitergebnisse von zwei Operationsmethoden bei Streßharninkontinenz mittels Introitussonographie und modifiziertem Gaudenz-Fragebogen mit folgenden Fragestellungen untersucht: - Korreliert der gemessene SBHA mit dem Grad der Inkontinenz? - Welche Methode der operativen Therapie der weiblichen Streßharninkontinenz (Burch vs. Kolporrhaphia anterior) zeigt gemessen am Symphysenblasenhalsabstand bzw. dem Befinden der Patientinnen (modifizierter Gaudenz-Fragebogen) die besseren Langzeitergebnisse? - Wie ändert sich der Symphysenblasenhalsabstand in der Langzeitbeobachtung seit der Operation? - Wie ist das subjektive Befinden der Patientinnen zur Problematik der Harninkontinenz vor und nach der Operation? - Wie hoch ist der Anteil einer rezidivierenden Streßharninkontinenz in beiden Kollektiven? 2. Patienten und Methode: Untersucht wurden 83 Patientinnen (mittleres Lebensalter 51 Jahre, SD 8,5 Jahre), die sich im Zeitraum zwischen 1989-1999 einer Kolporrhaphia anterior (N=60) oder einer Kolposuspension nach Burch (N=23) unterzogen hatten. Die Untersuchung gliederte sich in zwei Teilabschnitte:- Anamneseerhebung im persönlichen Gespräch und mittels modifiziertem Gaudenz-Fragebogen bezüglich der prä- und postoperativen Inkontinenzbeschwerden.- Klinische Untersuchung und Introitussonographie in Ruhe und unter Belastung. Patientinnen, bei denen eine kombinierte Operation durchgeführt wurde oder ein Descensus vorlag, wurden nicht in die Auswertung aufgenommen. 3. Ergebnisse: Eine anhaltende, vollständige Kontinenz konnte bei 21 von 83 Frauen (25,3%) diagnostiziert werden, wobei die Operationsmethode nach Burch tendenziell bessere Ergebnisse erbrachte. Bei 39 von 83 Frauen (47%) bestand eine gelegentliche Streßharninkontinenz, die in seltenen ungünstigen Konstellationen, wie bei Erkältung und voller Blase auftrat. Es war eine deutliche Verbesserung für die Frauen, gemessen an ihrer präoperativen Situation. Die Symptomatik: keine Streßharninkontinenz, gelegentliche Streßharninkontinenz, Rezidivinkontinenz zeigte eine Korrelation mit dem Symphysenblasenhalsabstand unter Belastung: - Je schwerer die Symptome der Streßharninkontinenz, umso niedriger ist der Symphysenblasenhalsabstand unter Belastung Bei der Kolposuspension nach Burch wurden postoperativ höhere mittlere SBHA-Werte in Ruhe (15,4mm), sowie unter Belastung (7,2mm), als bei der Kolporrhaphia anterior (13,6mm bzw. 3,4mm) gemessen. Die objektive Beurteilung der Langzeitergebnisse zeigt bei 18 von 23 Frauen (78,3%), die sich einer Kolposuspension nach Burch unterzogen hatten eine deutliche Besserung der Streßharninkontinenz. Dagegen gaben nur 17 von 60 Frauen (28,3%), bei denen eine Kolporrhaphia anterior durchgeführt wurde, eine deutliche Besserung der Streßharninkontinenz an. Auch bei der subjektiven Beurteilung zeigt die gruppenspezifische Auswertung, dass die Kolposuspension nach Burch signifikant (p=0,06) bessere Ergebnisse erzielte. Eine Rezidivinkontinenz wiesen 27,7% der Frauen auf, wobei sich der Anteil in der Gruppe der nach Burch operierten auf 21,7% (5 von 23 Frauen) und in der Gruppe der Kolporrhaphia anterior auf 30% (18 von 60 Frauen) belief. 4. Schlussfolgerung: Die Diagnostik der Streßharninkontinenz der Frau ist sicher und einfach durch die Introitussonographie gegeben, da die Inkontinenzsymptomatik zum Symphysenblasenhalsabstand unter Belastung korreliert. Aufgrund der signifikant besseren postoperativ subjektiven und der tendenziell besseren objektiven Ergebnisse in der operativen Therapie der Streßharninkontinenz der Frau, sollte die Kolposuspension nach Burch bei gegebener Indikation gegenüber der Kolporrhaphia anterior als Inkontinenz-Operation bevorzugt werden. Diese Entscheidung sollte jedoch unter Berücksichtigung der anatomischen Lageveränderungen getroffen werden. Auf der Basis unserer Ergebnisse, sollte im Rahmen weiterer klinischer Studien geklärt werden, inwiefern sich der Symphysenblasenhalsabstand in den Kollektiven der Kolporrhaphia anterior und der Kolposuspension nach Burch prä- versus postoperativ darstellt. Weiterhin wäre zur Beurteilung der Streßharninkontinenz eine zusätzliche Validierung durch urodynamische Messungen sinnvoll.Urinary incontinence is one of the most frequent diseases in women, and is seen by gynaecologists in increasing numbers. To remove impairments on the quality of life of patients, optimal diagnosis and therapy is crucial. With introital sonography, which is technically not challenging, the altered morphology of the pelvic floor of patients suffering from stress incontinence can easily be visualized. This shows the position of the bladder neck, as well as shape and position of the urethra, at rest and under pressure, in single pictures and as dynamic picture sequences. 1. Problems: This work examines long-term outcomes of two different operations for stress incontinence with the means of introital sonography and a modified Gaudenz-questionnaire. The following questions are addressed: - Is there any correlation of the measured distance (symphysis-bladder neck distance) and the degree of incontinence? - Which operation procedure for female stress incontinence (Burch colposuspension vs. anterior colporrhaphy) leads to a better outcome as assessed by the and by well-being of patients (modified Gaudenz-questionnaire)? - In the long term, is there any change in the distance of the symphysis-bladder neck distance after the operation? - What is the attitude of patients about incontinence before and after the operation? - Are there differences in relapses with respect to the chosen operation procedure? 2. Patients and Methods: 83 patients (mean age 51 years, SD 8,5 years) having a anterior colporrhaphy (N=60) or (N=23) in 1989 to 1999, were included. Examinations were performed in two parts as follows: - Personal anamnesis following a modified Gaudenz-questionnaire addressing incontinence symptoms before and after the operation - Clinical examination and introital sonography at rest and under pressure Patients with a combined operation (Burch colposuspension and anterior colporrhaphia) or with decensus were excluded. 3. Results: A long term and complete continence was observed by 21 of 83 women (25,3%), with Burch colposuspension seeming to lead to better results. 39 of 83 women (47%) reported an intermitting stress incontinence, which was associated with a rare combination of circumstances, like cough and full bladder. There was a clear improvement in the patients compared to their situation before the operation. The symptoms: no stress incontinence, intermitting stress incontinence and relapse correlated with symphysis-bladder neck distance under pressure: - The more severe the symptoms, the lower the symphysis-bladder neck distance under pressure. These distances were larger following Burch colposuspension (15,4mm at rest, 7,2mm under pressure) than following anterior colporrhaphy (13,6mm and 3,4mm, respectively). In 18 of 23 women (78,3%) after Burch colposuspension, an objective judgement of the long-term outcome showed a clear improvement of stress incontinence symptoms. In contrast, only 17 of 60 women (28,3%) after anterior colporrhaphy reported improvement. Concerning the subjective rating, group-specific analysis confirmed that Burch colposuspension lead to significantly better results (p=0,06). Relapse was observed in 27,7% of all women, with women after Burch colposuspension performing better (5 of 23 patients; 21,7%) compared to women after anterior colporrhaphy (18 of 60 patients; 30%). 4. Conclusion: With introital sonography, diagnosis of stress incontinence is straightforward, because symptoms of incontinence correlate with the symphysis-bladder neck distance under pressure. Given the significantly better postoperative outcome and the trend to better objective results, Burch colposuspension should be preferred to anterior colporrhaphy as operation method for stress incontinence. However, attention should be paid to possible anatomical alterations. Based on our results, further clinical studies are necessary to measure changes in the symphysis-bladder neck distance in larger groups of patients with respect to the method of operation (Burch colposuspension vs. anterior colporrhaphy). Moreover, additional urodynamic measurements should be taken to validate the assessment of stress incontinence

Heterogeneity between Core Needle Biopsy and Synchronous Axillary Lymph Node Metastases in Early Breast Cancer Patients: A Comparison of HER2, Estrogen and Progesterone Receptor Expression Profiles during Primary Treatment Regime

In breast cancer therapeutic decisions are based on the expression of estrogen (ER), progesterone (PR), the human epidermal growth factor 2 (HER2) receptors and the proliferation marker Ki67. However, only little is known concerning heterogeneity between the primary tumor and axillary lymph node metastases (LNM) in the primary site. We retrospectively analyzed receptor profiles of 215 early breast cancer patients with axillary synchronous LNM. Of our cohort, 69% were therapy naive and did not receive neoadjuvant treatment. Using immunohistochemistry, receptor status and Ki67 were compared between core needle biopsy of the tumor (t-CNB) and axillary LNM obtained during surgery. The discordance rates between t-CNB and axillary LNM were 12% for HER2, 6% for ER and 20% for PR. Receptor discordance appears to already occur at the primary site. Receptor losses might play a role concerning overtreatment concomitant with adverse drug effects, while receptor gains might be an option for additional targeted or endocrine therapy. Hence, not only receptor profiles of the tumor tissue but also of the synchronous axillary LNM should be considered in the choice of treatment

The Mechanical Fingerprint of Circulating Tumor Cells (CTCs) in Breast Cancer Patients

Circulating tumor cells (CTCs) are a potential predictive surrogate marker for disease monitoring. Due to the sparse knowledge about their phenotype and its changes during cancer progression and treatment response, CTC isolation remains challenging. Here we focused on the mechanical characterization of circulating non-hematopoietic cells from breast cancer patients to evaluate its utility for CTC detection. For proof of premise, we used healthy peripheral blood mononuclear cells (PBMCs), human MDA-MB 231 breast cancer cells and human HL-60 leukemia cells to create a CTC model system. For translational experiments CD45 negative cells—possible CTCs—were isolated from blood samples of patients with mamma carcinoma. Cells were mechanically characterized in the optical stretcher (OS). Active and passive cell mechanical data were related with physiological descriptors by a random forest (RF) classifier to identify cell type specific properties. Cancer cells were well distinguishable from PBMC in cell line tests. Analysis of clinical samples revealed that in PBMC the elliptic deformation was significantly increased compared to non-hematopoietic cells. Interestingly, non-hematopoietic cells showed significantly higher shape restoration. Based on Kelvin–Voigt modeling, the RF algorithm revealed that elliptic deformation and shape restoration were crucial parameters and that the OS discriminated non-hematopoietic cells from PBMC with an accuracy of 0.69, a sensitivity of 0.74, and specificity of 0.63. The CD45 negative cell population in the blood of breast cancer patients is mechanically distinguishable from healthy PBMC. Together with cell morphology, the mechanical fingerprint might be an appropriate tool for marker-free CTC detection

The Importance of Clinical Examination under General Anesthesia: Improving Parametrial Assessment in Cervical Cancer Patients

Background: Parametrial tumor involvement is an important prognostic factor in cervical cancer and is used to guide management. Here, we investigate the diagnostic value of clinical examination under general anesthesia (EUA) and magnetic resonance imaging (MRI) in determining parametrial tumor spread. Methods: Post-operative pathological findings of 400 patients with primary cervical cancer were compared to the respective MRI data and the results from EUA. The gynecological oncologist had access to the MR images during clinical assessment (augmented EUA, aEUA). Results: Pathologically proven parametrial tumor invasion was present in 165 (41%) patients. aEUA exhibited a higher accuracy than MRI alone (83% vs. 76%; McNemar’s odds ratio [OR] = 2.0, 95%CI 1.25–3.27, p = 0.003). Although accuracy was not affected by tumor size in aEUA, MRI was associated with a lower accuracy in tumors ≥2.5 cm (OR for a correct diagnosis compared to smaller tumors 0.22, p < 0.001). There was also a decrease in specificity when evaluating parametrial invasion by MRI in tumors ≥2.5 cm in diameter (p < 0.0001) compared to smaller tumors (< 2.5 cm). Body mass index had no influence on performance of either method. Conclusions: aEUA has the potential to increase the diagnostic accuracy of MRI in determining parametrial tumor involvement in cervical cancer patients

Prognostic impact of circulating tumor cells assessed with the CellSearch System (TM) and AdnaTest Breast (TM) in metastatic breast cancer patients: the DETECT study

Introduction: There is a multitude of assays for the detection of circulating tumor cells (CTCs) but a very limited number of studies comparing the clinical relevance of results obtained with different test methods. The DETECT trial for metastatic breast cancer patients was designed to directly compare the prognostic impact of two commercially available CTC assays that are prominent representatives of immunocytochemical and RT-PCR based technologies. Methods: In total, 254 metastatic breast cancer patients were enrolled in this prospective multicenter trial. CTCs were assessed using both the AdnaTest Breast Cancer and the CellSearch system according to the manufacturers' instructions. Results: With the CellSearch system, 116 of 221 (50%) evaluable patients were CTC-positive based on a cut-off level at 5 or more CTCs. The median overall survival (OS) was 18.1 months in CTC-positive patients. (95%-CI: 15.1-22.1 months) compared to 27 months in CTC-negative patients (23.5-30.7 months; p&lt;0.001). This prognostic impact for OS was also significant in the subgroups of patients with triple negative, HER2-positive and hormone receptor-positive/HER2-negative primary tumors. The progression free survival (PFS) was not correlated with CTC status in our cohort receiving different types and lines of systemic treatment (p = 0.197). In multivariate analysis, the presence of CTCs was an independent predictor for OS (HR: 2.7, 95%-CI: 1.6-4.2). When the AdnaTest Breast was performed, 88 of 221 (40%) patients were CTC-positive. CTC-positivity assessed by the AdnaTest Breast had no association with PFS or OS. Conclusions: The prognostic relevance of CTC detection in metastatic breast cancer patients depends on the test method. The present results indicate that the CellSearch system is superior to the AdnaTest Breast Cancer in predicting clinical outcome in advanced breast cancer

Immune Markers and Tumor-Related Processes Predict Neoadjuvant Therapy Response in the WSG-ADAPT HER2-Positive/Hormone Receptor-Positive Trial in Early Breast Cancer

Prognostic or predictive biomarkers in HER2-positive early breast cancer (EBC) may inform treatment optimization. The ADAPT HER2-positive/hormone receptor-positive phase II trial (NCT01779206) demonstrated pathological complete response (pCR) rates of ~40% following de-escalated treatment with 12 weeks neoadjuvant ado-trastuzumab emtansine (T-DM1) ± endocrine therapy. In this exploratory analysis, we evaluated potential early predictors of response to neoadjuvant therapy. The effects of PIK3CA mutations and immune (CD8 and PD-L1) and apoptotic markers (BCL2 and MCL1) on pCR rates were assessed, along with intrinsic BC subtypes. Immune response and pCR were lower in PIK3CA-mutated tumors compared with wildtype. Increased BCL2 at baseline in all patients and at Cycle 2 in the T-DM1 arms was associated with lower pCR. In the T-DM1 arms only, the HER2-enriched subtype was associated with increased pCR rate (54% vs. 28%). These findings support further prospective pCR-driven de-escalation studies in patients with HER2-positive EBC

Update breast cancer 2021 part 4 – prevention and early stages

This past year has seen new and effective options for further improving treatment outcome in many patients with early-stage breast cancer. Patients with hormone receptor-positive disease benefited significantly from the addition of the CDK4/6 inhibitor abemaciclib to endocrine adjuvant therapy. In triple-negative disease, data were presented for two treatment regimens. Patients with advanced disease (stage 2 and 3) benefit from neoadjuvant treatment with the immune checkpoint inhibitor pembrolizumab in combination with standard chemotherapy, regardless of PD-L1 expression. When neoadjuvant therapy has failed to achieve the desired remission in BRCA1 and BRCA2 mutations, the administration of the PARP inhibitor olaparib has demonstrated an impressive response. Other data address translational issues in HER2-positive breast cancer and neoadjuvant therapy approaches with the oral SERD giredestrant and the PARP inhibitor talazoparib. This review presents and analyses the findings of this yearʼ s most important study outcomes

Update breast cancer 2021 part 5 – advanced breast cancer

Despite the COVID 19 pandemic and mostly virtual congresses, innovation in the treatment of breast cancer patients continues at an unabated pace. This review summarises the current developments. Initial overall survival data for CDK4/6 inhibitor treatment in combination with an aromatase inhibitor as the first advanced line of therapy in treatment-naive postmenopausal patients have been published. Similarly, a trial comparing trastuzumab-deruxtecan versus trastuzumab-emtansine revealed a clear benefit regarding progression-free survival. Understanding of biomarkers making checkpoint inhibitor therapy particularly effective is increasing, and new compounds such as oral selective estrogen receptor destabilisers (SERDs) are entering clinical development and completing the first phase III trials

Update breast cancer 2022 part 4 – advanced-stage breast cancer

For the treatment of patients with advanced HER2-negative hormone receptor-positive breast cancer, several substances have been introduced into practice in recent years. In addition, other drugs are under development. A number of studies have been published over the past year which have shown either an advantage for progression-free survival or for overall survival. This review summarizes the latest results, which have been published at current congresses or in specialist journals, and classifies them in the clinical treatment context. In particular, the importance of therapy with CDK4/6 inhibitors – trastuzumab deruxtecan, sacituzumab govitecan and capivasertib – is discussed. For trastuzumab deruxtecan, an overall survival benefit in HER2-negative breast cancer with low HER2 expression (HER2-low expression) was reported in the Destiny-Breast-04 study. Similarly, there was an overall survival benefit in the FAKTION study with capivasertib. The lack of overall survival benefit for palbociclib in the first line of therapy raises the question of clinical classification