@article{StanglHaasEichneretal.2020, author = {Stangl, Stephanie and Haas, Kirsten and Eichner, Felizitas A. and Grau, Anna and Selig, Udo and Ludwig, Timo and Fehm, Tanja and St{\"u}bner, Tanja and Rashid, Asarnusch and Kerscher, Alexander and Bargou, Ralf and Hermann, Silke and Arndt, Volker and Meyer, Martin and Wildner, Manfred and Faller, Hermann and Schrauder, Michael G. and Weigel, Michael and Schlembach, Ulrich and Heuschmann, Peter U. and W{\"o}ckel, Achim}, title = {Development and proof-of-concept of a multicenter, patient-centered cancer registry for breast cancer patients with metastatic disease — the "Breast cancer care for patients with metastatic disease" (BRE-4-MED) registry}, series = {Pilot and Feasibility Studies}, volume = {6}, journal = {Pilot and Feasibility Studies}, doi = {10.1186/s40814-019-0541-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229149}, year = {2020}, abstract = {Background: Patients with metastatic breast cancer (MBC) are treated with a palliative approach with focus oncontrolling for disease symptoms and maintaining high quality of life. Information on individual needs of patients andtheir relatives as well as on treatment patterns in clinical routine care for this specific patient group are lacking or arenot routinely documented in established Cancer Registries. Thus, we developed a registry concept specifically adaptedfor these incurable patients comprising primary and secondary data as well as mobile-health (m-health) data. Methods: The concept for patient-centered "Breast cancer care for patients with metastatic disease"(BRE-4-MED)registry was developed and piloted exemplarily in the region of Main-Franconia, a mainly rural region in Germanycomprising about 1.3 M inhabitants. The registry concept includes data on diagnosis, therapy, progression, patient-reported outcome measures (PROMs), and needs of family members from several sources of information includingroutine data from established Cancer Registries in different federal states, treating physicians in hospital as well as inoutpatient settings, patients with metastatic breast cancer and their family members. Linkage with routine cancerregistry data was performed to collect secondary data on diagnosis, therapy, and progression. Paper and online-basedquestionnaires were used to assess PROMs. A dedicated mobile application software (APP) was developed to monitorneeds, progression, and therapy change of individual patients. Patient's acceptance and feasibility of data collection inclinical routine was assessed within a proof-of-concept study. Results: The concept for the BRE-4-MED registry was developed and piloted between September 2017 and May 2018.In total n= 31 patients were included in the pilot study, n= 22 patients were followed up after 1 month. Recordlinkage with the Cancer Registries of Bavaria and Baden-W{\"u}rttemberg demonstrated to be feasible. The voluntary APP/online questionnaire was used by n= 7 participants. The feasibility of the registry concept in clinical routine waspositively evaluated by the participating hospitals. Conclusion: The concept of the BRE-4-MED registry provides evidence that combinatorial evaluation of PROMs, needsof family members, and raising clinical parameters from primary and secondary data sources as well as m-healthapplications are feasible and accepted in an incurable cancer collective.}, language = {en} } @article{HartmannsbergerDopplerStauberetal.2020, author = {Hartmannsberger, Beate and Doppler, Kathrin and Stauber, Julia and Schlotter-Weigel, Beate and Young, Peter and Sereda, Michael W. and Sommer, Claudia}, title = {Intraepidermal nerve fiber density as biomarker in Charcot-Marie-Tooth disease 1A}, series = {Brain Communications}, volume = {2}, journal = {Brain Communications}, number = {1}, doi = {10.1093/braincomms/fcaa012}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229538}, year = {2020}, abstract = {Charcot-Marie-Tooth disease type 1A, caused by a duplication of the gene peripheral myelin protein 22 kDa, is the most frequent subtype of hereditary peripheral neuropathy with an estimated prevalence of 1:5000. Patients suffer from sensory deficits, muscle weakness and foot deformities. There is no treatment approved for this disease. Outcome measures in clinical trials were based mainly on clinical features but did not evaluate the actual nerve damage. In our case-control study, we aimed to provide objective and reproducible outcome measures for future clinical trials. We collected skin samples from 48 patients with Charcot-Marie-Tooth type 1A, 7 patients with chronic inflammatory demyelinating polyneuropathy, 16 patients with small fibre neuropathy and 45 healthy controls. To analyse skin innervation, 40-µm cryosections of glabrous skin taken from the lateral index finger were double-labelled by immunofluorescence. The disease severity of patients with Charcot-Marie-Tooth type 1A was assessed by the Charcot-Marie-Tooth neuropathy version 2 score, which ranged from 3 (mild) to 27 (severe) and correlated with age (P < 0.01, R = 0.4). Intraepidermal nerve fibre density was reduced in patients with Charcot-Marie-Tooth type 1A compared with the healthy control group (P < 0.01) and negatively correlated with disease severity (P < 0.05, R = -0.293). Meissner corpuscle (MC) density correlated negatively with age in patients with Charcot-Marie-Tooth type 1A (P < 0.01, R = -0.45) but not in healthy controls (P = 0.07, R = 0.28). The density of Merkel cells was reduced in patients with Charcot-Marie-Tooth type 1A compared with healthy controls (P < 0.05). Furthermore, in patients with Charcot-Marie-Tooth type 1A, the fraction of denervated Merkel cells was highly increased and correlated with age (P < 0.05, R = 0.37). Analysis of nodes of Ranvier revealed shortened paranodes and a reduced fraction of long nodes in patients compared with healthy controls (both P < 0.001). Langerhans cell density was increased in chronic inflammatory demyelinating polyneuropathy, but not different in Charcot-Marie-Tooth type 1A compared with healthy controls. Our data suggest that intraepidermal nerve fibre density might be used as an outcome measure in Charcot-Marie-Tooth type 1A disease, as it correlates with disease severity. The densities of Meissner corpuscles and Merkel cells might be an additional tool for the evaluation of the disease progression. Analysis of follow-up biopsies will clarify the effects of Charcot-Marie-Tooth type 1A disease progression on cutaneous innervation.}, language = {en} } @article{VoelkerWeigelStrehletal.2018, author = {V{\"o}lker, Hans-Ullrich and Weigel, Michael and Strehl, Annette and Frey, Lea}, title = {Levels of uPA and PAI-1 in breast cancer and its correlation to Ki67-index and results of a 21-multigene-array}, series = {Diagnostic Pathology}, volume = {13}, journal = {Diagnostic Pathology}, number = {67}, doi = {10.1186/s13000-018-0737-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176960}, year = {2018}, abstract = {Background: Conventional parameters including Ki67, hormone receptor and Her2/neu status are used for risk stratification for breast cancer. The serine protease urokinase plasminogen activator (uPA) and the plasminogen activator inhibitor type-1 (PAI-1) play an important role in tumour invasion and metastasis. Increased concentrations in tumour tissue are associated with more aggressive potential of the disease. Multigene tests provide detailed insights into tumour biology by simultaneously testing several prognostically relevant genes. With OncotypeDX\(^{®}\), a panel of 21 genes is tested by means of quantitative real-time polymerase chain reaction. The purpose of this pilot study was to analyse whether a combination of Ki67 and uPA/PAI-1 supplies indications of the result of the multigene test. Methods: The results of Ki67, uPA/PAI-1 and OncotypeDX\(^{®}\) were analysed in 25 breast carcinomas (luminal type, pT1/2, max pN1a, G2). A statistical and descriptive analysis was performed. Results: With a proliferation index Ki67 of < 14\%, the recurrence score (RS) from the multigene test was on average in the low risk range, with an intermediate RS usually resulting if Ki67 was > 14\%. Not elevated values of uPA and PAI-1 showed a lower rate of proliferation (average 8.5\%) than carcinomas with an increase of uPA and/or PAI-1 (average 13.9\%); p = 0.054, Student's t-test. When Ki67 was > 14\% and uPA and/or PAI-1 was raised, an intermediate RS resulted. These differences were significant when compared to cases with Ki67 < 14\% with non-raised uPA/PAI-1 (p < 0.03, Student's t-test). Without taking into account the proliferative activity, an intermediate RS was also verifiable if both uPA and PAI-1 showed raised values. Conclusion: A combination of the values Ki67 and uPA/PAI-1 tended to depict the RS to be expected. From this it can be deduced that an appropriate analysis of this parameter combination may be undertaken before the multigene test in routine clinical practice. The increasing cost pressure makes it necessary to base the implementation of a multigene test on ancillary variables and to potentially leave it out if not required in the event of a certain constellation of results (Ki67 raised, uPA and PAI-1 raised).}, language = {en} }