@article{LinzBrandsKertelsetal.2021, author = {Linz, Christian and Brands, Roman C. and Kertels, Olivia and Dierks, Alexander and Brumberg, Joachim and Gerhard-Hartmann, Elena and Hartmann, Stefan and Schirbel, Andreas and Serfling, Sebastian and Zhi, Yingjun and Buck, Andreas K. and K{\"u}bler, Alexander and Hohm, Julian and Lapa, Constantin and Kircher, Malte}, title = {Targeting fibroblast activation protein in newly diagnosed squamous cell carcinoma of the oral cavity - initial experience and comparison to [\(^{18}\)F]FDG PET/CT and MRI}, series = {European Journal of Nuclear Medicine and Molecular Imaging}, volume = {48}, journal = {European Journal of Nuclear Medicine and Molecular Imaging}, number = {12}, issn = {1619-7070}, doi = {10.1007/s00259-021-05422-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-307246}, pages = {3951-3960}, year = {2021}, abstract = {Purpose While [\(^{18}\)F]-fluorodeoxyglucose ([\(^{18}\)F]FDG) is the standard for positron emission tomography/computed tomography (PET/CT) imaging of oral squamous cell carcinoma (OSCC), diagnostic specificity is hampered by uptake in inflammatory cells such as neutrophils or macrophages. Recently, molecular imaging probes targeting fibroblast activation protein α (FAP), which is overexpressed in a variety of cancer-associated fibroblasts, have become available and might constitute a feasible alternative to FDG PET/CT. Methods Ten consecutive, treatment-na{\"i}ve patients (8 males, 2 females; mean age, 62 ± 9 years) with biopsy-proven OSCC underwent both whole-body [\(^{18}\)F]FDG and [\(^{68}\)Ga]FAPI-04 (FAP-directed) PET/CT for primary staging prior to tumor resection and cervical lymph node dissection. Detection of the primary tumor, as well as the presence and number of lymph node and distant metastases was analysed. Intensity of tracer accumulation was assessed by means of maximum (SUV\(_{max}\)) and peak (SUV\(_{peak}\) standardized uptake values. Histological work-up including immunohistochemical staining for FAP served as standard of reference. Results [\(^{18}\)F]FDG and FAP-directed PET/CT detected all primary tumors with a SUVmax of 25.5 ± 13.2 (FDG) and 20.5 ± 6.4 (FAP-directed) and a SUVpeak of 16.1 ± 10.3 ([\(^{18}\)F]FDG) and 13.8 ± 3.9 (FAP-directed), respectively. Regarding cervical lymph node metastases, FAP-directed PET/CT demonstrated comparable sensitivity (81.3\% vs. 87.5\%; P = 0.32) and specificity (93.3\% vs. 81.3\%; P = 0.16) to [\(^{18}\)F]FDG PET/CT. FAP expression on the cell surface of cancer-associated fibroblasts in both primary lesions as well as lymph nodes metastases was confirmed in all samples. Conclusion FAP-directed PET/CT in OSCC seems feasible. Future research to investigate its potential to improve patient staging is highly warranted.}, language = {en} } @article{PhilippAbbrederisHerrmannKnopetal.2015, author = {Philipp-Abbrederis, Kathrin and Herrmann, Ken and Knop, Stefan and Schottelius, Margret and Eiber, Matthias and L{\"u}ckerath, Katharina and Pietschmann, Elke and Habringer, Stefan and Gerngroß, Carlos and Franke, Katharina and Rudelius, Martina and Schirbel, Andreas and Lapa, Constantin and Schwamborn, Kristina and Steidle, Sabine and Hartmann, Elena and Rosenwald, Andreas and Kropf, Saskia and Beer, Ambros J and Peschel, Christian and Einsele, Hermann and Buck, Andreas K and Schwaiger, Markus and G{\"o}tze, Katharina and Wester, Hans-J{\"u}rgen and Keller, Ulrich}, title = {In vivo molecular imaging of chemokine receptor CXCR4 expression in patients with advanced multiple myeloma}, series = {EMBO Molecular Medicine}, volume = {7}, journal = {EMBO Molecular Medicine}, number = {4}, doi = {10.15252/emmm.201404698}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148738}, pages = {477-487}, year = {2015}, abstract = {CXCR4 is a G-protein-coupled receptor that mediates recruitment of blood cells toward its ligand SDF-1. In cancer, high CXCR4 expression is frequently associated with tumor dissemination andpoor prognosis. We evaluated the novel CXCR4 probe [\(^{68}\)Ga]Pentixafor for invivo mapping of CXCR4 expression density in mice xenografted with human CXCR4-positive MM cell lines and patients with advanced MM by means of positron emission tomography (PET). [\(^{68}\)Ga]Pentixafor PET provided images with excellent specificity and contrast. In 10 of 14 patients with advanced MM [\(^{68}\)Ga]Pentixafor PET/CT scans revealed MM manifestations, whereas only nine of 14 standard [\(^{18}\)F]fluorodeoxyglucose PET/CT scans were rated visually positive. Assessment of blood counts and standard CD34\(^{+}\) flow cytometry did not reveal significant blood count changes associated with tracer application. Based on these highly encouraging data on clinical PET imaging of CXCR4 expression in a cohort of MM patients, we conclude that [\(^{68}\)Ga]Pentixafor PET opens a broad field for clinical investigations on CXCR4 expression and for CXCR4-directed therapeutic approaches in MM and other diseases.}, language = {en} } @article{WinterSchulzSchmitteretal.2022, author = {Winter, Anna and Schulz, Stefan M. and Schmitter, Marc and Brands, Roman C. and Straub, Anton and K{\"u}bler, Alexander and Borgmann, Anna and Hartmann, Stefan}, title = {Oral-health-related quality of life in patients with medication-related osteonecrosis of the jaw: a prospective clinical study}, series = {International Journal of Environmental Research and Public Health}, volume = {19}, journal = {International Journal of Environmental Research and Public Health}, number = {18}, issn = {1660-4601}, doi = {10.3390/ijerph191811709}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-288141}, year = {2022}, abstract = {Medication-related osteonecrosis of the jaw (MRONJ) represents an adverse side effect of antiresorptive and antiangiogenic medications. It is associated with impaired quality of life, oral health, and oral function and can be classified into various stages. The purpose of this prospective clinical study is to evaluate the impact of stages I and II MRONJ on oral-health-related quality of life (OHRQoL) and related parameters. Patients' OHRQoL, satisfaction with life, oral discomfort, and oral health were assessed using the German version of the Oral Health Impact Profile (OHIP-G49), visual analog scales (VAS), and Satisfaction with Life Scale (SWLS) at baseline (T0), 10 days (T1), and 3 months after treatment (T2) in 36 patients. Data were analyzed using Kolmogorov-Smirnov test, two-way mixed ANOVAs, and follow-up Mann-Whitney U tests. The impact of treatment effects on the original seven OHIP domain structures and the recently introduced four-dimensional OHIP structure were evaluated using linear regression analysis. Thirty-six patients received surgical MRONJ treatment. Before treatment, patients' perceived OHRQoL, oral discomfort, oral health, and satisfaction with life were negatively affected by MRONJ. Surgical treatment significantly improved OHRQoL and related parameters (all p ≤ 0.012). This improvement was greater in patients with higher impairment at T0. OHRQoL and oral restrictions were still impaired after treatment in patients who needed prosthetic treatment. The four-dimensional structure revealed valuable information beyond the standard seven OHIP domains. Increased awareness of MRONJ risks and an interdisciplinary treatment approach for MRONJ patients are needed.}, language = {en} } @article{WinterSchulzSchmitteretal.2023, author = {Winter, Anna and Schulz, Stefan M. and Schmitter, Marc and M{\"u}ller-Richter, Urs and K{\"u}bler, Alexander and Kasper, Sylvia and Hartmann, Stefan}, title = {Comprehensive geriatric assessment and quality of life aspects in patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC)}, series = {Journal of Clinical Medicine}, volume = {12}, journal = {Journal of Clinical Medicine}, number = {17}, issn = {2077-0383}, doi = {10.3390/jcm12175738}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363096}, year = {2023}, abstract = {To define frailty in older cancer patients, the aim of this study was to assess the geriatric status and quality of life (QoL) aspects in patients suffering from recurrent/metastatic head and neck squamous cell carcinoma (r/m HNSCC) under palliative treatment. A comprehensive geriatric assessment (CGA) was performed on 21 r/m HNSCC patients at two defined assessments, and the QoL aspects and the impact of descriptive data were evaluated. The Kolmogorov-Smirnov test, Spearman's rho correlation, and two-way mixed ANOVA were used for statistical analysis. All patients were found to be "frail". Pain, fatigue, and the burden of illness were the highest-rated symptoms. Oral function and orofacial appearance were highly impaired. A significant impact of descriptive data on the CGA and QoL results was found (all p ≤ 0.05). Thus, the CGA results revealed high frailty, severe comorbidities, and high impairments in QoL aspects. The CGA and QoL results were negatively affected by the primary HNSCC treatment approach, the need for prosthetic treatment, and worse oral functional capacity. Therefore, frailty in r/m HNSCC patients seems to be multidimensional. The evaluation of the CGA and QoL aspects in r/m HNSCC patients can be recommended to detect special needs, organize aftercare, and improve the support for frail and vulnerable cancer patients to create a multidisciplinary treatment approach.}, language = {en} } @article{FuchsHartmannErnestusetal.2016, author = {Fuchs, Andreas and Hartmann, Stefan and Ernestus, Karen and Mutzbauer, Grit and Linz, Christian and Brands, Roman C. and K{\"u}bler, Alexander C. and M{\"u}ller-Richter, Urs D. A.}, title = {Mandibular intraosseous pseudocarcinomatous hyperplasia: a case report}, series = {Journal of Medical Case Reports}, volume = {16}, journal = {Journal of Medical Case Reports}, number = {268}, doi = {10.1186/s13256-016-1052-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146873}, year = {2016}, abstract = {Background Mandibular pseudocarcinomatous hyperplasia is a rare and generally benign pathology. We report on one of these rare cases. Case presentation The case history of a 73-year-old white man stated that he had a carcinoma of the oropharynx, which was primarily treated with radiotherapy and chemotherapy 4 years prior. As a result of radiotherapy he developed an osteoradionecrosis of his mandible and a consecutive pathological fracture of his left mandibular angle. Subsequent osteosynthesis was performed with a reconstruction plate. When we first saw him, his reconstruction plate was partially exposed with intraoral and extraoral fistulation. The resected bone of his defect-bordering jaw showed the typical pathohistological findings of an intraosseous mandibular pseudocarcinomatous hyperplasia. After a first reconstruction attempt with an iliac crest graft failed, definitive reconstruction of his mandible with a microvascular anastomosed fibula graft was achieved. Conclusions Intraosseous pseudocarcinomatous hyperplasia of the mandible is a rare differential diagnosis in maxillofacial surgery. Besides other benign epithelial neoplasms, such as calcifying epithelial odontogenic tumor, squamous odontogenic tumor, or different forms of ameloblastoma, the far more frequent invasive squamous cell carcinoma needs to be excluded. A misinterpretation of pseudocarcinomatous hyperplasia as squamous cell carcinoma must be avoided because it can lead to a massive overtreatment.}, language = {en} } @phdthesis{Hartmann2010, author = {Hartmann, Stefan}, title = {Vergleichende Analysen zwischen dreidimensionaler und konventioneller Kephalometrie bei Dysgnathiepatienten - Digitale Volumentomographie versus laterales Fernr{\"o}ntgenseitenbild}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-51407}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2010}, abstract = {In der vorliegenden retrospektiven Querschnittstudie wurde untersucht, ob sich zwei- und dreidimensionale Kephalometrie bei Dysgnathiepatienten unterscheidet. Zur Auswertung herangezogen wurden standardisiert aufgenommene Fernr{\"o}ntgenseitenbilder (FRS) und Cone-beam computed tomography (CB-CT)-Scans von 36 Patienten. Alle Patienten wurden in der Universit{\"a}tsklinik und Poliklink f{\"u}r Mund-, Kiefer- und Plastische Gesichtschirurgie aufgrund ihrer Dysgnathie operativ versorgt. Vor dem Vergleich der konventionellen Schichtaufnahmen und der korrespondierenden Volumina des gleichen Patienten miteinander, wurde zun{\"a}chst eine Pr{\"u}fung der Methode f{\"u}r beide Verfahren vorgenommen. Die Ergebnisse wurden statistisch deskriptiv und mithilfe eines Einstichproben-T-Test sowie eines F-Tests ausgewertet und interpretiert. Als Signifikanzniveau wurde p ≤ 0,05 gew{\"a}hlt. In der Studie konnte gezeigt werden, dass sich Untersucher bei der Auswertung eines dreidimensionalen Bildes h{\"a}ufiger und deutlicher unterscheiden als bei einer vergleichbaren Analyse auf Grundlage eines zweidimensionalen Bildes. Die Standardabweichungen waren f{\"u}r die Auswertungen der Volumina kleiner. Insbesondere die Messung der Unterkieferl{\"a}nge zeigte bei dreidimensionalen Bildern deutliche Unterschiede zwischen beiden Untersuchern. Die große Mehrzahl der anderen Messwerte zeigten hingegen keine relevanten Unterschiede zwischen den Untersuchern. Die Varianzen der Messungen waren f{\"u}r die 3-D-Kephalometrie in 71\% bzw. 79\% der F{\"a}lle kleiner als in einer vergleichbaren zweidimensionalen FRS-Messung. Es zeigte sich kein Anhalt f{\"u}r Zusammenh{\"a}nge zwischen der Anzahl der Referenzpunkte, die einer Messung zugrunde liegen und der entsprechenden Varianz des untersuchten Parameters. Beim direkten Vergleich zwischen zwei- und dreidimensionalem Bild wurden bei 66\% der paramedianen Parameter, aber nur bei 25\% der medianen Variablen gemittelte Differenzen von mehr als einem Millimeter bzw. Grad festgestellt. Es kommt also bei Parametern, die außerhalb der Sch{\"a}delmedian-Ebene liegen, h{\"a}ufiger zu klinisch relevanten Differenzen zwischen lateralem FRS und CB-CT. Die CB-CT kann zusammen mit der 3D-Kephalometrie bei Patienten mit fazialen Asymmetrien einen Zugewinn an Information gegen{\"u}ber der konventionellen Schichtaufnahme bedeuten. Hier zeigen sich die Vorteile einer {\"u}berlagerungsfreien und pr{\"a}zisen Darstellung des Gesichtssch{\"a}dels klar.}, subject = {Kraniometrie}, language = {de} } @article{OttoRubenwolfBurgeretal.2012, author = {Otto, Wolfgang and Rubenwolf, Peter C. and Burger, Maximilian and Fritsche, Hans-Martin and R{\"o}ßler, Wolfgang and May, Matthias and Hartmann, Arndt and Hofst{\"a}dter, Ferdinand and Wieland, Wolf F. and Denzinger, Stefan}, title = {Loss of aquaporin 3 protein expression constitutes an independent prognostic factor for progression-free survival: an immunohistochemical study on stage pT1 urothelial bladder cancer}, series = {BMC Cancer}, volume = {12}, journal = {BMC Cancer}, number = {459}, doi = {10.1186/1471-2407-12-459}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-135679}, year = {2012}, abstract = {Background: Treatment of patients with stage pT1 urothelial bladder cancer (UBC) continues to be a challenge due to its unpredictable clinical course. Reliable molecular markers that help to determine appropriate individual treatment are still lacking. Loss of aquaporin (AQP) 3 protein expression has previously been shown in muscle-invasive UBC. The aim of the present study was to investigate the prognostic value of AQP3 protein expression with regard to the prognosis of stage pT1 UBC. Method: AQP 3 protein expression was investigated by immunohistochemistry in specimens of 87 stage T1 UBC patients, who were diagnosed by transurethral resection of the bladder (TURB) and subsequent second resection at a high-volume urological centre between 2002 and 2009. Patients underwent adjuvant instillation therapy with Bacillus Calmette-Guerin (BCG). Loss of AQP3 protein expression was defined as complete absence of the protein within the whole tumour. Expression status was correlated retrospectively with clinicopathological and follow-up data (median: 31 months). Multivariate Cox regression analysis was used to assess the value of AQP3 tumour expression with regard to recurrence-free (RFS), progression-free (PFS) and cancer-specific survival (CSS). RFS, PFS and CSS were calculated by Kaplan-Meier analysis and Log rank test. Results: 59\% of patients were shown to exhibit AQP3-positive tumours, whereas 41\% of tumours did not express the marker. Loss of AQP3 protein expression was associated with a statistically significantly worse PFS (20\% vs. 72\%, p=0.020). This finding was confirmed by multivariate Cox regression analysis (HR 7.58, CI 1.29 - 44.68; p=0.025). Conclusions: Loss of AQP3 protein expression in pT1 UBC appears to play a key role in disease progression and is associated with worse PFS. Considering its potential prognostic value, assessment of AQP3 protein expression could be used to help stratify the behavior of patients with pT1 UBC.}, language = {en} } @article{HartmannLessnerMentzeletal.2014, author = {Hartmann, Stefan and Lessner, Grit and Mentzel, Thomas and K{\"u}bler, Alexander C. and M{\"u}ller-Richter, Urs}, title = {An adult spindle cell rhabdomyosarcoma in the head and neck region with long-term survival: a case report}, doi = {10.1186/1752-1947-8-208}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-110362}, year = {2014}, abstract = {Introduction Spindle cell rhabdomyosarcoma of the head and neck is a very rare tumor in adults. We report on one case with long-term survival. Case presentation A 41-year-old nonsmoking Caucasian man presented in June 2007 with a painless swelling under his tongue. A diagnosis of a soft tissue sarcoma, and a myofibrosarcoma in particular, was made via biopsy. After multimodal treatment, including local and systemic therapy, our patient remained disease-free until September 2010. The local recurrence was treated unsuccessfully with various chemotherapy regimens. In September 2011, our patient underwent surgical resection again, and a spindle cell rhabdomyosarcoma was diagnosed. To analyze the mismatch between the original diagnosis of a myofibrosarcoma and the second diagnosis, the two specimens were reassessed, and a final diagnosis of a spindle cell rhabdomyosarcoma was made. In 2012 and 2013, our patient suffered further recurrences that were surgically treated, and he is still alive with disease six years and 10 months after the initial diagnosis in June 2007. Conclusions In adults, the spindle cell rhabdomyosarcoma tumor is very rare in the head and neck region. In contrast to childhood tumors, spindle cell rhabdomyosarcoma in adulthood is often associated with a poor prognosis. In the present case, the radical surgical treatment might have helped to prolong the patient's overall survival, which has lasted more than six years. To our knowledge, this is the longest overall survival reported so far for this tumor entity in the head and neck region.}, language = {en} } @article{BoschertKlenkAbtetal.2020, author = {Boschert, Verena and Klenk, Nicola and Abt, Alexander and Raman, Sudha Janaki and Fischer, Markus and Brands, Roman C. and Seher, Axel and Linz, Christian and M{\"u}ller-Richter, Urs D. A. and Bischler, Thorsten and Hartmann, Stefan}, title = {The influence of Met receptor level on HGF-induced glycolytic reprogramming in head and neck squamous cell carcinoma}, series = {International Journal of Molecular Sciences}, volume = {21}, journal = {International Journal of Molecular Sciences}, number = {2}, issn = {1422-0067}, doi = {10.3390/ijms21020471}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235995}, year = {2020}, abstract = {Head and neck squamous cell carcinoma (HNSCC) is known to overexpress a variety of receptor tyrosine kinases, such as the HGF receptor Met. Like other malignancies, HNSCC involves a mutual interaction between the tumor cells and surrounding tissues and cells. We hypothesized that activation of HGF/Met signaling in HNSCC influences glucose metabolism and therefore substantially changes the tumor microenvironment. To determine the effect of HGF, we submitted three established HNSCC cell lines to mRNA sequencing. Dynamic changes in glucose metabolism were measured in real time by an extracellular flux analyzer. As expected, the cell lines exhibited different levels of Met and responded differently to HGF stimulation. As confirmed by mRNA sequencing, the level of Met expression was associated with the number of upregulated HGF-dependent genes. Overall, Met stimulation by HGF leads to increased glycolysis, presumably mediated by higher expression of three key enzymes of glycolysis. These effects appear to be stronger in Met\(^{high}\)-expressing HNSCC cells. Collectively, our data support the hypothesized role of HGF/Met signaling in metabolic reprogramming of HNSCC.}, language = {en} } @article{LinzFaberSchmidetal.2022, author = {Linz, Christian and Faber, Julian and Schmid, Reiner and Kunz, Felix and B{\"o}hm, Hartmut and Hartmann, Stefan and Schweitzer, Tilmann}, title = {Using a 3D asymmetry index as a novel form for capturing complex three-dimensionality in positional plagiocephaly}, series = {Scientific Reports}, volume = {12}, journal = {Scientific Reports}, doi = {10.1038/s41598-022-24555-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300427}, year = {2022}, abstract = {Positional plagiocephaly (PP) is the most common skull deformity in infants. Different classification systems exist for graduating the degree of PP, but all of these systems are based on two-dimensional (2D) parameters. This limitation leads to several problems stemming from the fact that 2D parameters are used to classify the three-dimensional (3D) shape of the head. We therefore evaluate existing measurement parameters and validate a newly developed 3D parameter for quantifying PP. Additionally, we present a new classification of PP based on a 3D parameter. 210 patients with PP and 50 patients without PP were included in this study. Existing parameters (2D and 3D) and newly developed volume parameters based on a 3D stereophotogrammetry scan were validated using ROC curves. Additionally, thresholds for the new 3D parameter of a 3D asymmetry index were assessed. The volume parameter 3D asymmetry index quantifies PP equally as well as the gold standard of 30° diagonal difference. Moreover, a 3D asymmetry index allows for a 3D-based classification of PP. The 3D asymmetry index can be used to define the degree of PP. It is easily applicable in stereophotogrammetric datasets and allows for comparability both intra- and inter-individually as well as for scientific analysis.}, language = {en} }