Oncologic Outcomes for Different Axillary Staging Techniques in Patients with Nodal-Positive Breast Cancer Undergoing Neoadjuvant Systematic Treatment: A Cancer Registry Study.

BACKGROUND: Targeted approaches such as targeted axillary dissection (TAD) or sentinel lymph node biopsy (SLNB) showed false-negative rates of < 10% compared with axillary lymph node dissection (ALND) in patients with nodal-positive breast cancer undergoing neoadjuvant systemic treatment (NAST). We aimed to evaluate real-world oncologic outcomes for different axillary staging techniques. METHODS: We identified nodal-positive breast cancer patients undergoing NAST from 2016 to 2021 from the state cancer registry of Baden-Wuerttemberg, Germany. Invasive disease-free survival (iDFS) was assessed using Kaplan-Meier statistics and multivariate Cox regression models (adjusted for age, ypN stage, ypT stage, and tumor biologic subtype). RESULTS: A total of 2698 patients with a median follow-up of 24.7 months were identified: 2204 underwent ALND, 460 underwent SLNB (255 with ≥ 3 sentinel lymph nodes [SLNs] removed, 205 with 1-2 SLNs removed), and 34 underwent TAD. iDFS 3 years after surgery was 69.7% (ALND), 76.6% (SLNB with ≥ 3 SLNs removed), 76.7% (SLNB with < 3 SLNs removed), and 78.7% (TAD). Multivariate Cox regression analysis showed no significant influence of different axillary staging techniques on iDFS (hazard ratio [HR] for SLNB with < 3 SLNs removed 0.96, 95% confidence interval [CI] 0.62-1.50; HR for SLNB with ≥ 3 SLNs removed 0.86, 95% CI 0.56-1.3; HR for TAD 0.23, 95% CI 0.03-1.64; ALND reference), and for ypN+ (HR 1.92, 95% CI 1.49-2.49), triple-negative breast cancer (HR 2.35, 95% CI 1.80-3.06), and ypT3-4 (HR 2.93, 95% CI 2.02-4.24). CONCLUSION: These real-world data provide evidence that patient selection for de-escalated axillary surgery for patients with nodal-positive breast cancer undergoing NAST was successfully adopted and no early alarm signals of iDFS detriment were detected.

[Incidence, therapy, and prognosis of prostate cancer in Baden-Württemberg: analysis based on cancer registry data]. / Inzidenz, Behandlung und Prognose des Prostatakarzinoms in Baden-Württemberg: Analyse anhand von Krebsregisterdaten.

BACKGROUND: Prostate cancer (PCa) is the most common solid tumor in men in Germany. Collection of epidemiological and clinical data has been centralized for several years due to legal requirements via the state cancer registries. Thus, the reporting of diagnosis, therapy, and progression of cancer is obligatory in Germany. These data needs to be processed based on the questions of the treating physicians. OBJECTIVES: Intention of this work was to present the development of new cases, disease stages, treatment procedures and prognosis of PCa in Baden-Württemberg (BW). METHODS: For this purpose, data of the cancer registry BW regarding patients with PCa first diagnosed between 2013 and 2021 were evaluated. The evaluation was performed using descriptive statistics, Χ2 test and Kaplan-Meier analysis. RESULTS: A total of 84,347 new diagnoses of PCa were reported. Clinical stage was present in 55.3% of patients. Assignment by International Society of Urological Pathology (ISUP) groups was present in 75.7%. A steady increase in primary diagnosis was evident through 2019. The proportion of primary metastatic disease decreased (2013: 19.6% vs. 2021: 12.0%), and the proportion of localized tumors increased (2013: 65.5% vs. 2021: 77.1%). Radical prostatectomy (RP) dominated the treatment of localized tumors with a mean of 60.1%. The proportion of robot-assisted surgery increased from 23.7% (2013) to 60.8% (2021) with a decrease in the R1 rate from 34.8 to 26.2%. Progression-free survival correlated closely with tumor stage and ISUP group. CONCLUSION: An increase in PCa cases and a decrease of advanced tumors were observed. Treatment was mostly surgical in localized stages, with increasing proportion of robotic-assisted RP. Early diagnosis and treatment are critical for long-term prognosis.

Clinical Characterization of HCC/CCA Mixed Cancers in a Population-based Cohort.

BACKGROUND AND AIMS: Primary liver cancer (PLC) ranks among of the most common cancers worldwide. Within this group, a minority of cases displays characteristics of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), known as combined hepatocellular cholangiocarcinoma (cHCC- CCA). Currently, there is no specific standardized therapy for these mixed tumors. Therefore, the aim of our study was to analyze the clinical course, treatment and outcome of cHCC-CCA patients in a European population-based registry. METHODS: We investigated 9,144 patients with PLC (6,622 HCC, 2,356 iCCA, and 166 cHCC-CCA) diagnosed between 2009 and 2020. All data were obtained from Clinical Cancer Registry of Baden-Württemberg (BW), Germany. RESULTS: In all three groups patients were predominantly male (82%, 57%, and 68% for HCC, iCCA and cHCC-CCA groups, respectively). 48% of cHCC-CCA patients were diagnosed as stage IV cancers, which was more than for HCC (31%) but less compared to CCA (64%). Overall median survival of cHCC-CCA patients was worse compared to HCC (9-13 months vs. 15.5 months, p<0.001) and rather comparable to CCA (11.8 months). CONCLUSIONS: Our data demonstrated that cHCC-CCA tumors appear to have a distinct clinical course with worse overall survival compared to HCC. Thus, identification of these cancers by histopathology is essential in order to further characterize this tumor entity and to provide accurate treatment to these patients.

Ca2+ dynamics correlates with phenotype and function in primary human neutrophils.

Central to the immune defense function of neutrophils is to sense, to move and to kill. Neutrophils acquire distinct cellular states necessary to fulfill these functions each associated with a particular phenotype. The cells constituting the neutrophil population are presumably not synchronized with respect to their actual state, e.g. due to maturity or preactivation. It is also likely that they exhibit a different degree of phenotypic plasticity (that is, the ability to switch to a particular state). Calcium is known to play a crucial role in neutrophils such as for cell motility. The present study focuses on characterizing the cell-to-cell variability at the morphological as well as at the level of calcium dynamics by studying single primary human neutrophils. We apply long-term multivariate live cell imaging to (i) characterize neutrophil phenotypes of different functional states, (ii) analyze the distribution of cells being in these states and, (iii) study the individual intracellular calcium response simultaneously with shape changes. We are able to differentiate the five distinct subpopulations of neutrophils based on quantitative parameters of cell morphology and motility. As a major result, we demonstrate that the calcium dynamics of individual cells correlates with their respective functional state. Finally, we see a number of cells that undergo spontaneous phenotypic changes from one cellular state to another. These events are preceded either by exhibiting the calcium dynamics of the future state or by switching to the respective calcium dynamics in parallel to switching the morphology. Based on our results we conclude that specific calcium dynamics carries crucial information for the function and phenotype of neutrophils.

Simplification of biochemical models: a general approach based on the analysis of the impact of individual species and reactions on the systems dynamics.

BACKGROUND: Given the complex mechanisms underlying biochemical processes systems biology researchers tend to build ever increasing computational models. However, dealing with complex systems entails a variety of problems, e.g. difficult intuitive understanding, variety of time scales or non-identifiable parameters. Therefore, methods are needed that, at least semi-automatically, help to elucidate how the complexity of a model can be reduced such that important behavior is maintained and the predictive capacity of the model is increased. The results should be easily accessible and interpretable. In the best case such methods may also provide insight into fundamental biochemical mechanisms. RESULTS: We have developed a strategy based on the Computational Singular Perturbation (CSP) method which can be used to perform a "biochemically-driven" model reduction of even large and complex kinetic ODE systems. We provide an implementation of the original CSP algorithm in COPASI (a COmplex PAthway SImulator) and applied the strategy to two example models of different degree of complexity - a simple one-enzyme system and a full-scale model of yeast glycolysis. CONCLUSION: The results show the usefulness of the method for model simplification purposes as well as for analyzing fundamental biochemical mechanisms. COPASI is freely available at http://www.copasi.org.

Accessible methods for the dynamic time-scale decomposition of biochemical systems.

MOTIVATION: The growing complexity of biochemical models asks for means to rationally dissect the networks into meaningful and rather independent subnetworks. Such foregoing should ensure an understanding of the system without any heuristics employed. Important for the success of such an approach is its accessibility and the clarity of the presentation of the results. RESULTS: In order to achieve this goal, we developed a method which is a modification of the classical approach of time-scale separation. This modified method as well as the more classical approach have been implemented for time-dependent application within the widely used software COPASI. The implementation includes different possibilities for the representation of the results including 3D-visualization. AVAILABILITY: The methods are included in COPASI which is free for academic use and available at www.copasi.org. CONTACT: irina.surovtsova@bioquant.uni-heidelberg.de SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

SYCAMORE--a systems biology computational analysis and modeling research environment.

UNLABELLED: SYCAMORE is a browser-based application that facilitates construction, simulation and analysis of kinetic models in systems biology. Thus, it allows e.g. database supported modelling, basic model checking and the estimation of unknown kinetic parameters based on protein structures. In addition, it offers some guidance in order to allow non-expert users to perform basic computational modelling tasks. AVAILABILITY: SYCAMORE is freely available for academic use at http://sycamore.eml.org. Commercial users may acquire a license. CONTACT: ursula.kummer@bioquant.uni-heidelberg.de.

Effects of compliance mismatch on blood flow in an artery with endovascular prosthesis.

The objective of this paper is to study the mechanical effects caused by the local stiffening of an artery (due to the vascular prosthesis, for instance). At the junction of the host artery and the more rigid implantant, the abrupt change in compliance creates an abnormal stress concentration that initiates an adaptive response in the vascular tissue. The roles of both fluid and solid mechanical phenomena must be considered in the prosthesis design optimization. In this context, even the simple models could provide helpful tools for designing process. We present here a model of blood flow in compliant vessel. The artery is supposed to be an orthotropical thin elastic shell. We obtain the solution by matched asymptotic expansions. The results prove the high flexure concentration close to the compliance jump. It is shown that the use of orthotropical graft may reduce the peak value of these shear forces to a remarkable extent. Waves reflected from the suture and pressure increase in the prosthesis are discussed. Compliance mismatch is shown to reduce the peak value of maximal wall shear stress.