TY - JOUR A1 - Wiegering, Armin A1 - Isbert, Christoph A1 - Dietz, Ulrich A. A1 - Kunzmann, Volker A1 - Ackermann, Sabine A1 - Kerscher, Alexander A1 - Maeder, Uwe A1 - Flentje, Michael A1 - Schlegel, Nicolas A1 - Reibetanz, Joachim A1 - Germer, Christoph-Thomas A1 - Klein, Ingo T1 - Multimodal therapy in treatment of rectal cancer is associated with improved survival and reduced local recurrence - a retrospective analysis over two decades N2 - Background The management of rectal cancer (RC) has substantially changed over the last decades with the implementation of neoadjuvant chemoradiotherapy, adjuvant therapy and improved surgery such as total mesorectal excision (TME). It remains unclear in which way these approaches overall influenced the rate of local recurrence and overall survival. Methods Clinical, histological and survival data of 658 out of 662 consecutive patients with RC were analyzed for treatment and prognostic factors from a prospectively expanded single-institutional database. Findings were then stratified according to time of diagnosis in patient groups treated between 1993 and 2001 and 2002 and 2010. Results The study population included 658 consecutive patients with rectal cancer between 1993 and 2010. Follow up data was available for 99.6% of all 662 treated patients. During the time period between 2002 and 2010 significantly more patients underwent neoadjuvant chemoradiotherapy (17.6% vs. 60%) and adjuvant chemotherapy (37.9% vs. 58.4%). Also, the rate of reported TME during surgery increased. The rate of local or distant metastasis decreased over time, and tumor related 5-year survival increased significantly with from 60% to 79%. Conclusion In our study population, the implementation of treatment changes over the last decade improved the patient’s outcome significantly. Improvements were most evident for UICC stage III rectal cancer. KW - Rectal cancer KW - Improved survival KW - TME Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-110606 ER - TY - JOUR A1 - Metzenmacher, Martin A1 - Váraljai, Renáta A1 - Hegedüs, Balazs A1 - Cima, Igor A1 - Forster, Jan A1 - Schramm, Alexander A1 - Scheffler, Björn A1 - Horn, Peter A. A1 - Klein, Christoph A. A1 - Szarvas, Tibor A1 - Reis, Hennig A1 - Bielefeld, Nicola A1 - Roesch, Alexander A1 - Aigner, Clemens A1 - Kunzmann, Volker A1 - Wiesweg, Marcel A1 - Siveke, Jens T. A1 - Schuler, Martin A1 - Lueong, Smiths S. T1 - Plasma Next Generation Sequencing and Droplet Digital-qPCR-Based Quantification of Circulating Cell-Free RNA for Noninvasive Early Detection of Cancer JF - Cancers N2 - Early detection of cancer holds high promise for reducing cancer-related mortality. Detection of circulating tumor-specific nucleic acids holds promise, but sensitivity and specificity issues remain with current technology. We studied cell-free RNA (cfRNA) in patients with non-small cell lung cancer (NSCLC; n = 56 stage IV, n = 39 stages I-III), pancreatic cancer (PDAC, n = 20 stage III), malignant melanoma (MM, n = 12 stage III-IV), urothelial bladder cancer (UBC, n = 22 stage II and IV), and 65 healthy controls by means of next generation sequencing (NGS) and real-time droplet digital PCR (RT-ddPCR). We identified 192 overlapping upregulated transcripts in NSCLC and PDAC by NGS, more than 90% of which were noncoding. Previously reported transcripts (e.g., HOTAIRM1) were identified. Plasma cfRNA transcript levels of POU6F2-AS2 discriminated NSCLC from healthy donors (AUC = 0.82 and 0.76 for stages IV and I–III, respectively) and significantly associated (p = 0.017) with the established tumor marker Cyfra 21-1. cfRNA yield and POU6F2-AS transcript abundance discriminated PDAC patients from healthy donors (AUC = 1.0). POU6F2-AS2 transcript was significantly higher in MM (p = 0.044). In summary, our findings support further validation of cfRNA detection by RT-ddPCR as a biomarker for early detection of solid cancers. KW - liquid biopsy KW - cfRNA KW - cancer KW - ddPCR KW - NGS KW - POU6F2-AS2 KW - early detection Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200553 SN - 2072-6694 VL - 12 IS - 2 ER - TY - JOUR A1 - Lenz, Dominic A1 - Pahl, Jens A1 - Hauck, Fabian A1 - Alameer, Seham A1 - Balasubramanian, Meena A1 - Baric, Ivo A1 - Boy, Nikolas A1 - Church, Joseph A. A1 - Crushell, Ellen A1 - Dick, Anke A1 - Distelmaier, Felix A1 - Gujar, Jidnyasa A1 - Indolfi, Giuseppe A1 - Lurz, Eberhard A1 - Peters, Bianca A1 - Schwerd, Tobias A1 - Serranti, Daniele A1 - Kölker, Stefan A1 - Klein, Christoph A1 - Hoffmann, Georg F. A1 - Prokisch, Holger A1 - Greil, Johann A1 - Cerwenka, Adelheid A1 - Giese, Thomas A1 - Staufner, Christian T1 - NBAS Variants Are Associated with Quantitative and Qualitative NK and B Cell Deficiency JF - Journal of Clinical Immunology N2 - Purpose Biallelic pathogenic NBAS variants manifest as a multisystem disorder with heterogeneous clinical phenotypes such as recurrent acute liver failure, growth retardation, and susceptibility to infections. This study explores how NBAS-associated disease affects cells of the innate and adaptive immune system. Methods Clinical and laboratory parameters were combined with functional multi-parametric immunophenotyping methods in fifteen NBAS-deficient patients to discover possible alterations in their immune system. Results Our study revealed reduced absolute numbers of mature CD56dim natural killer (NK) cells. Notably, the residual NK cell population in NBAS-deficient patients exerted a lower potential for activation and degranulation in response to K562 target cells, suggesting an NK cell–intrinsic role for NBAS in the release of cytotoxic granules. NBAS-deficient NK cell activation and degranulation was normalized upon pre-activation by IL-2 in vitro, suggesting that functional impairment was reversible. In addition, we observed a reduced number of naïve B cells in the peripheral blood associated with hypogammaglobulinemia. Conclusion In summary, we demonstrate that pathogenic biallelic variants in NBAS are associated with dysfunctional NK cells as well as impaired adaptive humoral immunity. KW - NBAS KW - inborn error of immunity KW - NK cell deficiency KW - B cell deficiency KW - vesicle trafficking KW - familial hemophagocytic lymphohistiocytosis Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-308362 SN - 0271-9142 SN - 1573-2592 VL - 41 IS - 8 ER -