C Hann von Weyhern

Universität Witten/Herdecke, Witten, North Rhine-Westphalia, Germany

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Publications (60)191.44 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The objective was to determine the role of dose intensive induction chemotherapy in patients with soft tissue sarcomas (STS) that were considered unresectable. Treatment consisted of 2-3 cycles of doxorubicin (Dox) and ifosfamide (Ifo) followed by high dose chemotherapy with ifosfamide, carboplatin, etoposide (HD-ICE) plus peripheral blood stem cell transplantation (PBSCT). 30 out of 631 consecutive patients, median age 46 years (21-62), with high grade STS were included. 29 patients completed at least 2 cycles of Dox/Ifo. HD-ICE was withheld because of progressive disease (PD) in 5 patients, neurotoxicity in 6 cases, insufficient peripheral blood stem cell (PBSC) mobilization, complete remission (CR) and refusal in 1 patient each. HD-ICE was associated with non-haematological grade III toxicity including emesis, mucositis, fever, neurotoxicity, and transaminase level elevation. Two additional patients attained a partial response after HD-ICE. Overall, 24 of 30 (80 %) patients underwent surgery, with complete tumor resections in 19 patients (63 % of all patients, 79 % of the operated subgroup); however, 2 of these required amputation. After a median follow up period of 50 months in surviving patients (range, 26-120), 5-year PFS and OS rates were 39 % and 48 %, respectively. Induction chemotherapy plus consolidation HD-ICE is generally feasible, but is associated with significant neurotoxicity. The advantage of HD-ICE over conventional dose chemotherapy plus external beam radiation therapy (EBRT) in non-resectable disease remains unproven.
    Investigational New Drugs 10/2013; · 3.50 Impact Factor
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    ABSTRACT: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a standard procedure for intrathoracic lymph node biopsies. The newly developed cryo-needle operates in a similar way to the EBUS-TBNA but is able to obtain specimens for histological evaluation. The purpose of this animal study was to evaluate the feasibility, effect, and safety of the cryo-needle biopsies. Four EBUS-guided cryo-needle biopsies were obtained from a mediastinal lymph node of a healthy pig. In an open surgery approach, cryo-needle biopsies using activation times of 1, 2, and 3 s (A1/A2/A3) and needle biopsies using a 21-gauge EBUS-TBNA needle were obtained from mesenteric lymph nodes. Cryo-needle biopsies A2 were performed with (A2+) and without (A2-) an oversheath. The size, weight, percentage of lymphatic tissue and artefact-free area of each cryobiopsy were evaluated. Smears were made with the TBNA-needle aspirates to determine the number of lymphocytes per high-power field (HPF). The bleeding duration was measured. We successfully obtained EBUS-guided cryo-needle biopsies. The area and weight of the biopsies A3 and A2+ were significantly larger compared with A1 (1.7 ± 0.8 and 1.4 ± 0.3 vs. 0.9 ± 0.4 mm(2); 5.2 ± 2.4 and 3.4 ± 1.8 vs. 1.5 ± 0.7 mg). The percentage of lymphatic tissue of the cryobiopsies was 90 ± 25 and 98 % of samples were artefact-free. The number of lymphocytes/HPF of TBNA-needle smears was 128 ± 54.3. There was no difference in bleeding duration between the techniques. The cryo-needle yields large histological specimens of high quality.
    Beiträge zur Klinik der Tuberkulose 08/2013; · 2.06 Impact Factor
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    ABSTRACT: To measure perfusion in different lung cancer subtypes and compare results with histopathological/immunohistochemical results. Seventy-two consecutive untreated patients with lung cancer (40 adenocarcinomas, 20 squamous cell, and 12 small cell lung cancers) were enrolled. A 40-second volume perfusion computed tomography of the tumor bulk was obtained. Blood flow (BF), blood volume (BV), and transit constant were determined. Tumor volume and tumor necrosis were determined on contrast-enhanced computed tomography. Pathologic specimens were assessed for microvessel density (MVD), hypoxia-induced transcription (hif-1/-2), and proliferation (Ki-67). Higher MVD is associated with higher BF and BV. Higher tumor grade leads to lower BF but increased necrosis and tumor volume. Markers of hypoxia were independent from perfusion parameters, extent of necrosis or MVD. Blood flow, BV, and MVD were not significantly different among lung cancer subtypes. Transit constant was significantly reduced in small cell lung cancer versus adenocarcinoma. Perfusion values are related to MVD and tumor grade but vary considerably among lung cancer subtypes.
    Journal of computer assisted tomography 01/2013; 37(1):15-21. · 1.38 Impact Factor
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    ABSTRACT: Advanced adult soft-tissue sarcomas (STSs) are rare tumors with a dismal prognosis and limited systemic treatment options. STSs may originate from mesenchymal stem cells (MSCs); the latter have mainly been isolated from adult bone marrow as plastic-adherent cells with differentiation capacity into mesenchymal tissues. Recently, a panel of antibodies has been established that allows for the prospective isolation of primary MSCs with high selectivity. Similar to cancer stem cells in other malignancies, sarcoma stem cells may bear immunophenotypic similarity with the corresponding precursor, that is, MSCs. We therefore set out to establish the expression pattern of MSC markers in sarcoma cell lines and primary tumor samples by flow cytometry. In addition, fibroblasts from different sources were examined. The results document a significant amount of MSC markers shared by sarcoma cells. The expression pattern includes uniformly expressed markers, as well as MSC markers that only stained subpopulations of sarcoma cells. Expression of W5C5, W8B2 (tissue nonspecific alkaline phosphatase [TNAP]), CD344 (frizzled-4), and CD271 marked subpopulations displaying increased proliferation potential. Moreover, CD271+ cells displayed in vitro doxorubicin resistance and an increased capacity to form spheres under serum-free conditions. Interestingly, another set of antigens, including the bona fide progenitor cell markers CD117 and CD133, were not expressed. Comparative expression patterns of novel MSC markers in sarcoma cells, as well as fibroblasts and MSCs, are presented. Our data suggest a hierarchical cytoarchitecture of the most common adult type sarcomas and introduce W5C5, TNAP, CD344, and CD271 as potential sarcoma progenitor cell markers.
    Stem cells translational medicine. 12/2012;
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    ABSTRACT: The expression of Heat Shock Proteins (HSPs) is increased in various cancers and has been shown to correlate with biological tumor behaviour. This study aimed to investigate the impact of HSP70, HSP60 and HSP27 expression in colon cancer. HSP expression was determined by immunohistochemistry on a tissue microarray with 355 primary resected colon carcinomas of all stages. Expression patterns were correlated with pathologic features (UICC pTNM category, tumor grading) and survival. Expression of HSP27, HSP60 and HSP70 ranged from negative to high. There was no correlation between HSP27, HSP60 and HSP70 expression among each other and with UICC pT category, presence of lymph node or distant metastases or tumor grading. High HSP70 expression was associated with worse overall survival (p < 0.001) and was an independent prognostic factor (p = 0.004) in multivariate analysis including the pathological parameters mentioned above. For patients without lymph node or distant metastases (UICC stages I/II) and with complete tumor excision, HSP70 expression was the only independent prognostic factor for survival (p = 0.001) and superior to UICC pT category. In left sided UICC stage I/II carcinomas, high HSP27 expression also had adverse prognostic impact and was an independent prognostic factor (p = 0.016) besides HSP70 (p = 0.002). High HSP70 and HSP27 expression is associated with worse clinical outcome in colon cancer. Determination of tumoral HSP70 and HSP27 may be used as additional biomarker for risk stratification especially for UICC stage I/II patients.
    Cellular oncology (Dordrecht). 04/2012; 35(3):197-205.
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    ABSTRACT: Renal cell carcinoma can cause various paraneoplastic syndromes including metabolic and hematologic disturbances. Paraneoplastic hypereosinophilia has been reported in a variety of hematologic and solid tumors. We present the first case in the literature of severe paraneoplastic hypereosinophilia in a patient with renal cell carcinoma. A 46 year-old patient patient with a history of significant weight loss, reduced general state of health and coughing underwent radical nephrectomy for metastasized renal cell carcinoma. Three weeks after surgery, the patient presented with excessive peripheral hypereosinophilia leading to profound neurological symptoms due to cerebral microinfarction. Systemic treatment with prednisolone, hydroxyurea, vincristine, cytarabine, temsirolimus and sunitinib led to reduction of peripheral eosinophils but could not prevent rapid disease progression of the patient. At time of severe leukocytosis, a considerable increase of cytokines associated with hypereosinophilia was measurable. Paraneoplastic hypereosinophilia in patients with renal cell carcinoma might indicate poor prognosis and rapid disease progression. Myelosuppressive therapy is required in symptomatic patients.
    BMC Urology 03/2012; 12:7. · 1.69 Impact Factor
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    ABSTRACT: The aim of this study was to investigate correlations between glucose metabolism registered by (18)F-FDG PET/CT and tumor perfusion quantified by volume perfusion CT and immunohistochemical markers Ki67 and microvessel density (MVD) in patients with non-small cell lung cancer (NSCLC). Between February 2010 and April 2011, 24 consecutive patients (21 women, 3 men; mean age ± SD, 67.6 ± 6.8 y; age range, 55.6-81.3 y) with histologically proven NSCLC (14 adenocarcinoma, 9 squamous cell lung carcinoma [SCC], and 1 mixed adenocarcinoma and SCC) underwent (18)F-FDG PET/CT and additional volume perfusion CT. Maximum standardized uptake value (SUV(max)), mean SUV, and the metabolic tumor volume were used for (18)F-FDG uptake quantification. Blood flow (BF), blood volume (BV), flow extraction product (K(trans)), and standardized perfusion value (SPV) were determined as CT perfusion parameters. Both perfusion parameters and (18)F-FDG uptake values were subsequently related to the histologic subtypes, proliferation marker Ki67, MVD according to CD34 staining, and total tumor volume. Mean SUV, SUV(max), and the metabolic tumor volume (mL) were 5.8, 8.7, and 32.3, respectively, in adenocarcinoma and 8.5, 12.9, and 16.8, respectively, in SCC. Mean BF (mL/100 mL/min), mean BV (mL/100 mL), and K(trans) (mL/100 mL/min) were 35.4, 7.3, and 27.8, respectively, in adenocarcinoma and 35.5, 10.0, and 27.8, respectively, in SCC. Moderate correlations were found between the (18)F-FDG PET/CT parameters and Ki67 as well as between CT perfusion parameters and MVD but not vice versa. For all tumors, the following correlations were found: between SUV(max) and Ki67, r = 0.762 (P = 0.017); between SUV(max) and MVD, r = -0.237 (P = 0.359); between mean BF and Ki67, r = -0.127 (P = 0.626); and between mean BF and MVD, r = 0.467 (P = 0.059). Interestingly, correlations between the BF-metabolic relationship and total tumor volume were higher in SCC (r = 0.762, P = 0.017) than in adenocarcinoma (r = -0.0791, P = 0.788). (18)F-FDG uptake correlates with Ki67, whereas BF, BV, and K(trans) correlate with MVD. Therefore, (18)F-FDG uptake and perfusion parameters provide complementary functional information. An improved tumor profiling will be beneficial for both prognosis and therapy response evaluation in these tumors.
    Journal of Nuclear Medicine 03/2012; 53(4):521-9. · 5.77 Impact Factor
  • Journal of Clinical Oncology 11/2011; 29(33):e799-802. · 18.04 Impact Factor
  • U Grosse, C Hann von Weyhern, S D Ioanoviciu, M Horger
    RöFo - Fortschritte auf dem Gebiet der R 06/2011; 183(6):501-4. · 2.76 Impact Factor
  • B Kunze, C von Weyhern, T Kluba
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    ABSTRACT: Myositis proliferans is a soft tissue neoplasia with rare incidence. In the most cases, it is localized in the region of the neck, shoulder, pelvis and thigh. Due to its rapid growth and histological picture, the tumour may appear as a malignant neoplasia. We report the case of a 29-year-old woman suffering from an increasing painful swelling of the left proximal lower leg. Performed biopsies and histological examinations provided the diagnosis of myositis proliferans adjacent to the fibula, which responded to local resection and did not recur after 2 years. We show the importance of adequate diagnostic and therapeutic approach to avoid unnecessary and probably radical overtherapy of the patient.
    MUSCULOSKELETAL SURGERY 05/2011; 95(3):255-7.
  • Claus Hann von Weyhern, Björn L D M Brücher
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    ABSTRACT: Tissues are complicated three-dimensional structures, composed of different types of interacting cells. Since the cell population of interest might constitute only a minor fraction of the total tissue volume, the problem of tissue heterogeneity has been a major barrier to the molecular analysis of normal versus diseased tissue. Thus, tissue microdissection represents one of the most promising techniques in molecular pathology offering the link between morphology and genetic analysis since it was established in the early 1970s. These first applications and further developments in the techniques enable preparation of morphologically well described and circumscribed cell populations of either tumor cells or surrounding tissue or even cytology specimens without contamination of unwanted cells. Laser capture microdissection is suitable for the dissection of both paraffin embedded and fresh frozen material. Further applications of the dissected genomic material are isolation of DNA and RNA as described later on followed by PCR or RT-PCR and sequencing.
    Methods in molecular biology (Clifton, N.J.) 01/2011; 755:197-202. · 1.29 Impact Factor
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    Dominik Ketelsen, Claus Hann von Weyhern, Marius Horger
    Journal of Clinical Oncology 11/2010; 28(33):e678-9. · 18.04 Impact Factor
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    ABSTRACT: Paratesticular fibrous pseudotumor (nodular periorchitis, inflammatory pseudotumor of the spermatic cord) is a rare, benign condition of unknown etiology characterized by solitary or multiple intrascrotal nodules composed of dense fibrous tissue with a variable, sometimes sparse inflammatory infiltrate. Based on certain similarities to other fibroinflammatory disorders characterized by infiltrates of IgG4-expressing plasma cells and recently subsumed under the heading of IgG4-mediated diseases, we investigated the plasma cell distribution and immunoglobulin isotypes in three cases of paratesticular fibrous and inflammatory pseudotumor. All three cases showed a high number of IgG4-positive plasma cells with an IgG4 to IgG ratio of 44-48%. This finding indicates that paratesticular fibrous pseudotumor might belong to the growing list of IgG4-related diseases, which by now includes such diverse entities as retroperitoneal fibrosis, sclerosing pancreatitis and cholangitis, Riedel's thyroiditis, or sclerosing sialadenitis.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 10/2010; 458(1):109-13. · 2.68 Impact Factor
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    ABSTRACT: Because (18)F-FDG PET alone has only limited value in metastatic germ cell tumors (GCTs), we investigated the addition of 3'-deoxy-3'-(18)F-fluorothymidine (FLT) to (18)F-FDG for early response monitoring and prediction of the histology of residual tumor masses in patients with metastatic GCT. Eleven patients with metastatic GCT were examined with both (18)F-FDG PET/CT and (18)F-FLT PET/CT before chemotherapy, after the first cycle of chemotherapy (early response), and 3 wk after completion of chemotherapy. In 1 patient with negative (18)F-FLT PET/CT results before chemotherapy, no further (18)F-FLT scanning was performed. PET images were analyzed visually and, using standardized uptake values (SUVs), semiquantitatively. The results were compared with the findings of CT and tumor marker levels and validated by histopathologic examination of resected residual masses, including Ki-67 immunostaining (7 patients), or by clinicoradiologic follow-up for at least 6 mo (4 patients). A responder was defined as a patient showing the presence of necrosis, a complete remission, or a marker-negative partial remission within a minimum progression-free interval of 6 mo. Early treatment response was judged according to the criteria of the European Organization for Research and Treatment of Cancer. Before chemotherapy, reference lesions showed increased (18)F-FDG uptake (mean SUV, 8.8; range, 2.9-15.0) in all patients and moderate (18)F-FLT uptake (mean SUV, 3.7; range, 1.7-9.7) in 10 of 11 patients. After 1 cycle of chemotherapy, mean SUV decreased in responders and nonresponders by 64% and 60%, respectively, for (18)F-FDG (P = 0.8) and by 58% and 48%, respectively, for (18)F-FLT (P = 0.5). After the end of chemotherapy, mean SUV decreased in responders and nonresponders by 85% and 73%, respectively, for (18)F-FDG (P = 0.1) and by 68% and 65%, respectively, for (18)F-FLT (P = 0.8). The results of early and final PET were inconsistent in 6 of 11 patients for (18)F-FDG and in 4 of 10 patients for (18)F-FLT. Both patients with teratoma had false-negative results on both (18)F-FDG and (18)F-FLT. The sensitivity, specificity, positive predictive value, and negative predictive value for detection of viable tumor after 1 cycle of chemotherapy were 60%, 33%, 43%, and 50%, respectively, for (18)F-FDG and 60%, 80%, 75%, and 67%, respectively, for (18)F-FLT PET/CT. The respective values after the end of chemotherapy were 20%, 100%, 100%, and 60% for (18)F-FDG and 0%, 100%, 0%, and 50% for (18)F-FLT PET/CT. PET-negative residual masses after chemotherapy of metastatic GCT still require resection, since the low negative predictive value of (18)F-FDG PET for viable tumor cannot be improved by application of (18)F-FLT.
    Journal of Nuclear Medicine 06/2010; 51(6):845-53. · 5.77 Impact Factor
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    ABSTRACT: Cryoextraction is a procedure used for the recanalization of obstructed airways caused by visible exophytic endobronchial tumor. Biopsy samples obtained by this technique have been shown to be useful for histological assessment. The aim of the present animal study was to systematically evaluate biopsy size, histological quality and bleeding risk after cryobiopsy with new, flexible cryoprobes in comparison with forceps biopsy, serving as the gold standard. Biopsies were obtained from anesthetized pigs with the flexible bronchoscopy technique, and evaluated histologically with respect to their size and quality. Bleeding frequency, bleeding duration and histological changes in the biopsy bed were also recorded. Cryobiopsies were significantly larger than forceps biopsies. The size of cryobiopsies was dependent on the freezing time. The histological quality of the cryobiopsy specimenswas not impaired by the freezing process, whereas forceps biopsies showed typical crush artifacts. Despite the larger defects left in the tracheobronchial system after cryobiopsy, bleeding frequency and duration were not higher compared to forceps biopsy. Since cryobiopsy sampling is not associated with a higher bleeding risk compared with forceps biopsy, this new biopsy technique offers--in addition to a good specimen quality--a safe and valuable tool with the potential of improving the outcome of diagnostic endoscopy.
    Respiration 02/2010; 80(2):127-32. · 2.62 Impact Factor
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    ABSTRACT: Tumor dissemination is frequent in gastric cancer and implies a poor prognosis. Cure is only achievable provided an accurate staging is performed at primary diagnosis. In previous studies we were able to show a relevant impact of increased phosphoglycerate kinase 1 expression (PGK1; a glycolytic enzyme) on invasive properties of gastric cancer in-vivo and in-vitro. Thus the aim of the present study was to evaluate the effect of enhanced PGK1 expression in gastric cancer employing magnetic resonance (MR)-imaging combined with positron emission tomography (PET), a recently emerging new high resolution imaging technique in a mouse model. A metastatic nude mouse model simulating human gastric cancer behavior by orthotopic tumor implantation was established. Mice were divided into one control group (n=5) and two experimental groups (n=30) divided by half in animals baring tumors from MKN45-cells and MKN45-cells with plasmid-mediated overexpression of PGK1. In the course of tumor growth MR-imaging and PET/MRI fusion was performed. Successively experimental animals were examined macroscopically and histopathologically regarding growth, metastasis and PGK1 expression. Elevated PGK1 expression increased invasive and metastatic behavior of implanted gastric tumors significantly. MR/PET- imaging results in-vivoand subsequent ex-vivo findings concerning tumor growth and metastasis correlated excellently and could be underlined by concordant immuohistochemical PGK1 staining. Consistent in-vivo findings suggest that PGK1 might be crucially involved in gastric malignancy regarding growth and metastasis, which was also underlined by novel imaging techniques. Thus, PGK1 may be exploited as a prognostic marker and/or be of potential therapeutic value preventing malignant dissemination.
    Cellular Physiology and Biochemistry 01/2010; 26(2):147-54. · 3.42 Impact Factor
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    ABSTRACT: The evaluation of subepithelial tumors of the stomach is normally the domain of gastroscopy and endoscopic ultrasound. We investigated these rare tumors using transabdominal B-mode ultrasound and performed perfusion analysis of these tumors with contrast enhanced ultrasound. Patients with gastrointestinal stromal tumors (GIST, n = 3), leiomyoma (n = 1) and schwannoma (n = 1) were routinely examined using conventional B-mode-ultrasound, colour Doppler ultrasound and contrast-enhanced ultrasound (contrast media: Sonovue; ultrasound device: Siemens Acuson Sequoia 512). Gastroscopy, endosonography with puncture of the subepithelial tumor and computed tomography were also performed in all patients. After surgery, the resected stomach tumors were correlated with the preoperative imaging findings. All calculated tumor sizes using any imaging modalities showed a good correlation with the macroscopic tumor sizes ex-vivo. Histologically increased tumor size of the GISTs was correlated with large, central avascular areas. The GISTs and the leiomyoma presented with mixed echogenicity in B-mode-ultrasound. Colour Doppler ultrasound was able to detect some vessels in the periphery of the tumor only. Using contrast-enhanced ultrasound the GISTs and the leiomyoma presented hypervascular. The contrast pattern of these lesions was from the periphery to the centre or diffuse or a progressive centrifugal fill in during the arterial phase. We also registered slowly progressive washout starting at the end of the arterial phase and increasing into the late phase. The contrast media behaviour in the schwannoma was different from that describt above within the GISTs: it was noted to have a diffuse intralesional pattern at the start of the arterial phase followed by an early, rapidly progressing washout-phenomenon. In our pilot study B-mode transabdominal ultrasound was able to visualise gastric subepithelial tumors larger than three centimetre. Contrast-enhanced ultrasound is a proven method in clinical practice for the perfusion analysis of gastric subepithelial tumors. It can also be used for the planning of ultrasound-guided biopsies to avoid punctures of necrotic tumor parts.
    Clinical hemorheology and microcirculation 01/2010; 45(2-4):225-32. · 3.40 Impact Factor
  • Zeitschrift Fur Gastroenterologie - Z GASTROENTEROL. 01/2010; 48(08).
  • Zeitschrift Fur Gastroenterologie - Z GASTROENTEROL. 01/2010; 48(08).
  • Zeitschrift Fur Gastroenterologie - Z GASTROENTEROL. 01/2010; 48(08).

Publication Stats

723 Citations
191.44 Total Impact Points

Institutions

  • 2013
    • Universität Witten/Herdecke
      • Chair of Internal Medicine I
      Witten, North Rhine-Westphalia, Germany
    • Städtischen Klinikum München
      München, Bavaria, Germany
  • 2010
    • Pathologisches Institut Bremerhaven
      Bremerhaven, Bremen, Germany
  • 2005–2010
    • Technische Universität München
      • • Medizinische Klinik und Poliklinik III - Hämatologie/Onkologie
      • • Clinic and Polyclinic for Surgery
      München, Bavaria, Germany
  • 2007
    • Deutsches Herzzentrum München
      München, Bavaria, Germany