F Grabellus

Universität Duisburg-Essen, Duisburg, North Rhine-Westphalia, Germany

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Publications (22)42.69 Total impact

  • Article: Neoadjuvant treatment improves capsular integrity and the width of the fibrous capsule of high-grade soft-tissue sarcomas.
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    ABSTRACT: BACKGROUND: Neoadjuvant treatment is thought to improve resection with margin-negative surgery in locally advanced soft-tissue sarcomas (STS). Treatment-induced alterations of the tumor peripheryhave not yet been microscopically evaluated. OBJECTIVE: This histopathological study compared limb STS with primary resection and those that had undergone neoadjuvant treatment, emphasizing microscopic changes of the fibrous capsule (FC) and reactive zone (RZ) after neoadjuvant treatment. PATIENTS AND METHODS: Patients with primary high-grade limb sarcomas (N = 76) which have not previously been treated were included. Of those, 37 were primarily resected and 39 were treated with one of the following neoadjuvant treatment modalities: 7x chemotherapy (CTX), 3x radiotherapy (RT), 15x isolated limb perfusion (ILP), 8x CTX + RT, and 6x CTX + ILP. Sizes of the FC and RZ were microscopically measured, and FC-integrity was documented. Histopathologic regression was expressed as a percent. RESULTS: Only 35.1% of untreated sarcomas showed an intact FC. We observed significantly higher capsular integrity after treatment (76.9%). Additionally, the average width of the FC (0.21 mm vs. 0.61 mm) and RZ (0.67 mm vs. 1.48 mm) increased significantly. The extent of histopathologic regression showed a correlation with capsular integrity and width. The combination of two treatment modalities (CTX + RT or ILP) showed strongest effects at the tumor periphery. CONCLUSIONS: Neoadjuvant treatment stabilizes the tumor periphery in STS (e.g., the capsule). Concerning local treatment strategies, these novel histopathologic insights might significantly influence the decision as to whether primary resection is advisable in advanced local soft-tissue sarcoma.
    European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 10/2012; · 2.56 Impact Factor
  • Article: Isolierte Extremitätenperfusion zur lokalen Tumorkontrolle an den Gliedmaßen
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    ABSTRACT: Die proliferativen Randzonen determinieren beim hoch malignen Weichteilsarkom (WTS) die Rezidivhäufigkeit. Bei der Resektion Die proliferativen Randzonen determinieren beim hoch malignen Weichteilsarkom (WTS) die Rezidivhäufigkeit. Bei der Resektion großer und tief lokalisierter Sarkome ist aber das Erreichen sog. weiter Sicherheitsabstände unter der Maßgabe des Erhalts großer und tief lokalisierter Sarkome ist aber das Erreichen sog. weiter Sicherheitsabstände unter der Maßgabe des Erhalts von Funktion und Gliedmaße häufig limitiert. Selbst knappe Abstände können zuweilen nicht erreicht werden. Durch neoadjuvante von Funktion und Gliedmaße häufig limitiert. Selbst knappe Abstände können zuweilen nicht erreicht werden. Durch neoadjuvante Therapieverfahren kann mittels Devitalisierung oder Schrumpfung des Tumors eine spätere Resektion deutlich verbessert oder Therapieverfahren kann mittels Devitalisierung oder Schrumpfung des Tumors eine spätere Resektion deutlich verbessert oder erst ermöglicht werden. Die isolierte Extremitätenperfusion mit TNF-α und Melphalan (TM-ILP) gilt dabei als das effektivste erst ermöglicht werden. Die isolierte Extremitätenperfusion mit TNF-α und Melphalan (TM-ILP) gilt dabei als das effektivste Therapieverfahren. Mehrere Studien berichten über Remissionsraten von bis zu 80% mit Verbesserung der späteren Resektion und Therapieverfahren. Mehrere Studien berichten über Remissionsraten von bis zu 80% mit Verbesserung der späteren Resektion und Erhalt von Funktion und Gliedmaße. Einen besonders hohen Stellenwert besitzt die TM-ILP für Patienten mit synchron metastasierten Erhalt von Funktion und Gliedmaße. Einen besonders hohen Stellenwert besitzt die TM-ILP für Patienten mit synchron metastasierten großen WTS der Gliedmaßen. Im Gegensatz zu den zeitlichen Verzögerungen, die meist mit den ausgedehnten chirurgischen Resektionen großen WTS der Gliedmaßen. Im Gegensatz zu den zeitlichen Verzögerungen, die meist mit den ausgedehnten chirurgischen Resektionen verbunden sind, kann nach TM-ILP schon innerhalb weniger Tage die Systemtherapie erfolgen. Diese Therapiemodalität sollte verbunden sind, kann nach TM-ILP schon innerhalb weniger Tage die Systemtherapie erfolgen. Diese Therapiemodalität sollte in tertiären Behandlungszentren angeboten werden können. in tertiären Behandlungszentren angeboten werden können. Clear and wide safety margins are required in surgical resections of high-grade soft tissue sarcomas (STS) due to the proliferation Clear and wide safety margins are required in surgical resections of high-grade soft tissue sarcomas (STS) due to the proliferation patterns at the periphery of the tumors. But resections of large and deep-seated tumors are often limited by close or even patterns at the periphery of the tumors. But resections of large and deep-seated tumors are often limited by close or even marginal resection margins in order to salvage a limb and its function. Hence, neoadjuvant treatment strategies may improve marginal resection margins in order to salvage a limb and its function. Hence, neoadjuvant treatment strategies may improve subsequent surgical resection by shrinking and devitalizing the local tumor. Of these treatment modalities, hyperthermic isolated subsequent surgical resection by shrinking and devitalizing the local tumor. Of these treatment modalities, hyperthermic isolated limb perfusion with TNF-α and melphalan (TM-ILP) provides the most effective deterioration of advanced and even nonresectable limb perfusion with TNF-α and melphalan (TM-ILP) provides the most effective deterioration of advanced and even nonresectable STS by immediate destruction of the vasculature. Different studies have reported remission rates of up to 80%, with improved STS by immediate destruction of the vasculature. Different studies have reported remission rates of up to 80%, with improved subsequent resection as well as minimization of the surgical trauma usually associated with the resection of high-grade sarcomas. subsequent resection as well as minimization of the surgical trauma usually associated with the resection of high-grade sarcomas. Obviously, TM-ILP has its greatest potential in advanced STS of the limbs with concomitant metastatic disease. Patients are Obviously, TM-ILP has its greatest potential in advanced STS of the limbs with concomitant metastatic disease. Patients are ready for systemic treatment strategies within days of deterioration of the local tumor by TM-ILP. This treatment modality ready for systemic treatment strategies within days of deterioration of the local tumor by TM-ILP. This treatment modality should be offered to these patients and should be available in tertiary cancer centers. should be offered to these patients and should be available in tertiary cancer centers.
    Der Onkologe 04/2012; 15(4):382-388. · 0.17 Impact Factor
  • Article: Riesenzelltumoren des Weichgewebes (mit niedrig-malignem Potenzial) in Operationsnarben
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    ABSTRACT: Riesenzelltumoren des Weichgewebes mit niedrig-malignem Potenzial („giant cell tumor of soft tissue“, GCT-ST) sind seltene primäre „Low-grade-Weichteilsarkome“. Das klinische Verhalten und die Histologie sind dem Riesenzelltumor des Knochens sehr ähnlich. Wir berichten über zwei GCT-ST-Fälle, die klinisch als Rezidiv einer anderen Tumorentität behandelt wurden. Die beiden voroperierten Tumoren waren ein hochdifferenziertes Leiomyosarkom des Weichgewebes und ein In-situ-Plattenepithelkarzinom der Haut. Das Auftreten von GCT-ST in chirurgischem Narbengewebe ist bisher noch nicht beschrieben und lässt an einen ätiologischen Zusammenhang zwischen reparativen Gewebeprozessen und dem Entstehen derartiger Läsionen denken. Die teils kurze Zeitspanne zwischen Operation und Auftreten des GCT-ST erscheint für die Entwicklung eines unabhängigen Zweittumors ungewöhnlich kurz, was die unscharfe Grenze zwischen reaktiven und neoplastischen fibrösen oder sogenannten fibrohistiozytären Läsionen unterstreicht. Giant cell tumor of soft tissue (GCT-ST) is a rare primary soft tissue tumor with low malignant potential. It is clinically and pathologically similar to the giant cell tumor of the bone. Two cases of GCT-ST in surgical scars are reported. Both tumors were initially regarded as tumor relapses of a leiomyosarcoma of deep soft tissue and a dermal in situ squamous cell carcinoma, respectively. The development of GCT-ST in surgical scars has not been observed previously. These findings suggest chronic inflammation and tissue repair as etiological factors in the development of GCT-ST. The period of time between initial surgical intervention and the development of the GCT-ST seems to be unusually short for the development of a “true” second neoplasm, which may underline the sometimes diffuse border between reactive “pseudosarcomatous” and neoplastic fibro-histiocytic lesions.
    Der Pathologe 04/2012; 30(5):401-406. · 0.67 Impact Factor
  • Article: Neuromonitoring in a porcine model of acute hepatic failure.
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    ABSTRACT: Cerebral oedema has been noted to occur frequently in patients dying of fulminant hepatic failure. Therefore, in the present study, multimodal neuromonitoring was evaluated in an animal model of hepatectomy. Acute liver failure was surgically induced in swine by complete hepatectomy (n = 8). Intracranial pressure monitoring via a ventricular drainage system, electroencephalogram and recording of visually evoked potentials were used to establish a continuous neuromonitoring system. Measurements of liquor and serum ammonia (NH(3)) levels were taken at later stages of the trial in an approach to widen monitoring. Serial monitoring of the electroencephalogram revealed progressive slowing of the frequency with decreasing amplitude. Monitoring of the intracranial pressure with a subdural pressure transducer demonstrated a progressive and reproducible elevation. Increase in blood NH(3) was observed. Anaesthesia was terminal. In all cases death was caused by cardiocirculatory insufficiency, confirmed by autopsy. At autopsy, brain tissue of the animals was found to be swollen showing flattened cortical gyri. In conclusion, the technique of extended neuromonitoring offers an advanced option for monitoring animal models of fulminant hepatic failure for further developments and investigations.
    Laboratory Animals 04/2011; 45(3):174-8. · 1.21 Impact Factor
  • Article: Liver transplantation for metastasized extragastrointestinal stromal tumor: a case report and an overview of literature.
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    ABSTRACT: A 63-year-old woman underwent living donor liver transplantation for hepatic metastases of an extragastrointestinal stromal tumor (EGIST) originating from the rectovaginal space. Due to a multifocal extrahepatic tumor recurrence, treatment with imatinib mesylate was started after extensive pharmacokinetic studies to rule out possible interactions with immunosuppressives. We performed several re- resections for EGIST recurrence thereafter. At the last follow-up, 17 years after primary tumor resection and 10 years after living donor liver transplantation, the patient is symptom-free under immunosuppressive and imatinib mesylate treatments with a 2-cm stable recurrent pararectal EGIST. To our knowledge, this is the only report published on a patient who underwent transplantation for hepatic EGIST metastases with a posttransplantation follow-up of 10 years and the first report on living donor liver transplantation for metastasized EGIST. This is the first description of pharmacokinetics of imatinib and its main active metabolite CGP74588 in a liver transplant recipient.
    Transplantation Proceedings 11/2010; 42(9):3843-8. · 1.00 Impact Factor
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    Article: Differential miRNA expression profiles in variants of papillary thyroid carcinoma and encapsulated follicular thyroid tumours.
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    ABSTRACT: Recent studies showed a significant upregulation of distinct microRNAs (miRNAs) in papillary thyroid carcinoma (PTC). The objective of this study was to explore whether this upregulation could also be assigned to distinct histomorphological variants of PTC, especially the follicular variant and other encapsulated follicular thyroid tumours. We used total RNA of 113 formalin-fixed paraffin-embedded tissues of 50 PTCs ((10 conventional type (PTC-CT), 10 tall cell variants (PTC-TCVs), 30 follicular variants (PTC-FVs)), 10 follicular adenomas (FAs), 10 multinodular goitres (MNGs), 21 follicular thyroid carcinomas and 22 well-differentiated tumours of unknown malignant potential (WDT-UMP) to analyse the miRNA expression pattern of five selected miRNAs (146b, 181b, 21, 221 and 222) using RT-PCR TaqMan miRNA assay to explore the diagnostic utility of this method. The mean values of the expression pattern of all miRNAS in PTCs show a statistically significant difference from those in MNG and FA with fold changes up to 90 for miRNA 146b, P<0.001. No differences in expression pattern could be showed between MNG and FA. The PTC-FVs differ significantly from FA in all five miRNAS, from MNG in three and from WDT-UMP in one miRNA with fold changes between 1.7 and 21.2, but failed to be of diagnostic value regarding individual cases with substantial overlaps. We conclude that analysis of a set of five selected miRNAS distinguish common variants of PTC from FA/MNG but failed to be a useful diagnostic method in individual and doubtful cases, especially in the differential diagnosis of encapsulated follicular thyroid tumours.
    British Journal of Cancer 12/2009; 102(2):376-82. · 5.04 Impact Factor
  • Article: [Giant cell tumors of soft tissue arising in surgical scars].
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    ABSTRACT: Giant cell tumor of soft tissue (GCT-ST) is a rare primary soft tissue tumor with low malignant potential. It is clinically and pathologically similar to the giant cell tumor of the bone. Two cases of GCT-ST in surgical scars are reported. Both tumors were initially regarded as tumor relapses of a leiomyosarcoma of deep soft tissue and a dermal in situ squamous cell carcinoma, respectively. The development of GCT-ST in surgical scars has not been observed previously. These findings suggest chronic inflammation and tissue repair as etiological factors in the development of GCT-ST. The period of time between initial surgical intervention and the development of the GCT-ST seems to be unusually short for the development of a "true" second neoplasm, which may underline the sometimes diffuse border between reactive "pseudosarcomatous" and neoplastic fibro-histiocytic lesions.
    Der Pathologe 05/2009; 30(5):401-6. · 0.67 Impact Factor
  • Article: Analysis of deregulated miRNAs is helpful to distinguish poorly differentiated thyroid carcinoma from papillary thyroid carcinoma.
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    ABSTRACT: Poorly differentiated thyroid carcinoma (PDTC) is defined as a malignant follicular cell derived neoplasm, both morphologically and biologically intermediate between well differentiated and anaplastic thyroid carcinoma (ATC). In the present study we investigated the expression levels of two distinct sets of miRNAs ('set 1': miRNA-146b, -181b, -21, -221, -222, all shown to be significantly upregulated in papillary thyroid carcinoma [PTC]; 'set 2': miRNA-30d, -125b, -26a, -30a-5p, and let7c, all downregulated in ATC) in a series of 15 PDTC (including 3 mixed PDTC/PTC), 9 'pure' PTC, and 9 ATC. Compared to normal thyroid tissue all 'set 1' miRNAs were significantly upregulated in PTC (p<0.001); in ATC 4/5 miRNAs were upregulated (p<0.001) whereas in PDTC the expression levels of all 5 miRNAs did not differ significantly from normal thyroid. All miRNAs of 'set 2' were significantly upregulated in PTC (p<0.004) and downregulated in ATC (p<0.03); in PDTC only 3/5 were downregulated (p<0.011). All 10 miRNAs investigated differed significantly (p<0.003) between PTC and PDTC. In the histologically differentiated PTC compound of mixed PDTC/PTC cases, however, miRNA expression levels of all 10 miRNAs investigated lacked significant difference from those found in the PDTC compound, whereas 6/10 miRNAs differed significantly from 'pure' PTC. Our results indicate that analysis of distinct sets of miRNAs represent useful tools to distinguish PDTC from 'pure' PTC. Additionally our findings suggest that lack of deregulation of some miRNAs may select a subset of PTC prone to progression to PDTC.
    Hormone and Metabolic Research 04/2009; 41(6):475-81. · 2.19 Impact Factor
  • Article: Lack of correlation between BRAF V600E mutational status and the expression profile of a distinct set of miRNAs in papillary thyroid carcinoma.
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    ABSTRACT: Recent studies demonstrated a significant upregulation of distinct microRNAs (miRNAs), small endogenous RNAs that regulate gene expression, in papillary thyroid carcinoma (PTC). In the pathogenesis of PTC the T1799A (V600E) BRAF mutation is the most common genetic alteration leading to a constitutive activation of the MAPK pathway. The aim of the present study was to elucidate a possible correlation between BRAF mutational status and a distinct miRNA expression profile. In a series of 221 PTC we determined the BRAF V600E mutational status using DNA-sequencing and correlated the occurrence of the mutation with a variety of clinicopathologcial data. The miRNA expression profile of five selected subtypes (miRNA-146b, -181b, -21, -221, -222) in two matched cohorts of BRAF positive (n=28) and wildtype cases (n=26) was examined by RT-PCR TaqMan miRNA assay. The BRAF V600E mutation was significantly found in PTCs with extrathyroidal extension (p <0.001). Among them, V600E was even significantly associated with smaller tumour size of 1 cm or less (microcarcinomas; p<0.003) and the follicular (p=0.017) and tall cell variant (p=0.015). By calculating relative changes in miRNA gene expression no differences in fold changes could be detected between BRAF positive and wildtype PTC suggesting that BRAF has no regulatory influence on the expression of the five examined miRNAs. However, our study confirmed the diagnostic utility of this distinct set of miRNAs to detect PTC by significant fold changes in at least 3 miRNAs (miRNA-146b, -221, -222) irrespective of its histological variant.
    Hormone and Metabolic Research 04/2009; 41(6):482-7. · 2.19 Impact Factor
  • Article: COX-2 expression in highly aggressive thyroid malignancies - indication for a possible therapeutic option?
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    ABSTRACT: Both anaplastic thyroid carcinoma (ATC) and angiosarcoma of the thyroid (AST) are highly aggressive malignancies with very limited therapeutic options. Since selective inhibition of COX-2, for example, by celecoxib has been shown to suppress both tumour formation and progression, we investigated COX-2 protein expression in a series of ATC and AST (26 cases each) using immunohistochemistry. COX-2 expression was demonstrated in 13 ATC (50%) and 11 AST (42%); a strong COX-2 expression in more than 50% of vital tumour cells was found in 5 ATC and 5 AST, respectively. Although a recently performed phase II trial applying celecoxib failed overall to halt tumour progression in differentiated thyroid carcinoma, the two cases with partial or complete remission noted in this study were related to tumours with immunohistochemically proven strong COX-2 expression. The strong COX-2 expression observed in approximately 20% of our ATC and AST samples may thus indicate selective patients with a possible therapeutic option for an otherwise fatal disease.
    Hormone and Metabolic Research 01/2009; 41(4):314-9. · 2.19 Impact Factor
  • Article: Effectiveness of regional chemotherapy with TNF-alpha/melphalan in advanced soft tissue sarcoma of the extremities.
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    ABSTRACT: Hyperthermic isolated limb perfusion with tumour necrosis factor alpha (TNF-alpha) and melphalan was repeatedly reported to achieve extraordinarily high clinical remission rates in advanced and non-resectable soft tissue sarcoma of the limbs, thus avoiding imminent mutilation or amputation for most of those patients. With the limb being isolated throughout the extracorporal perfusion, high doses of recombinant TNF-alpha as well as melphalan can be applied. Basically, TNF-alpha directly affects the vasculature of the tumour and induces a severe inflammation with consecutive deterioration of the tumour capillaries. Furthermore, TNF-alpha increases the tumour-selective uptake of melphalan into the tumour cells thus leading to synergy of antivascular targeted treatment and antineoplastic effects of highest dose chemotherapy supplemented by hyperthermia. Meanwhile, a lot of sarcoma centres in Europe adopted this technique and established referral programmes for patients with non-resectable soft tissue sarcomas of the limbs. Despite these programmes many patients still do not get offered hyperthermic ILP with TNF-alpha and melphalan as a treatment option and modality. This article summarizes multimodality in treatment of soft tissue sarcoma of the limbs and reviews the current status of melphalan-based ILP with TNF-alpha (TM-ILP) and its results, to enable comparison and critical consideration of other treatment options.
    International Journal of Hyperthermia 06/2008; 24(3):193-203. · 1.92 Impact Factor
  • Article: Relationship and prognostic significance of phospho-(serine 166)-murine double minute 2 and Akt activation in node-negative breast cancer with regard to p53 expression.
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    ABSTRACT: The Akt signalling pathway plays a central role in tumourigenesis. Activation of Akt is related to a more aggressive phenotype in various human cancers, including breast cancer. Its activation contributes to cancer progression via pleiotropic effects, including suppression of apoptosis and modulation of cell cycle regulation. Murine double minute 2 (MDM2) is an oncoprotein that inhibits the function of p53 tumour suppressor protein. Cell culture studies show that Akt-related phosphorylation of MDM2 at serine 166 allows MDM2 to gain nuclear entry and fulfil its p53 regulating function. This study was designed to analyse the relationship of phospho-MDM2 (pMDM2) expression with Akt activation to determine a possible prognostic relevance of pMDM2 in node-negative breast cancer with respect to Akt activation and p53 status. pMDM2, phospho-Akt (pAkt) and p53 protein expression status were analysed immunohistochemically in 121 paraffin-embedded breast cancer cases. Expression of pMDM2 correlated with Akt activation (P<0.001). Univariate analysis identified pMDM2 as a prognostic factor (P=0.0458) in node-negative breast cancers. The unfavourable prognostic significance was even more pronounced in tumours with a pMDM2(+)/pAkt(+) immunophenotype (P=0.0205). Stratification into a p53-negative subgroup further strengthened the adverse prognostic influence. These data confirm that MDM2 phosphorylation at serine 166 is mediated by Akt kinase. Besides the prognostic impact of pMDM2, our findings suggest that Akt-mediated modulation of the MDM2/p53 complex contributes to increased tumour aggressiveness especially in p53-negative breast cancers. However, due to the relatively small number of patients in this cohort, the results obtained need to be confirmed by larger cohorts.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 01/2006; 448(1):16-23. · 2.49 Impact Factor
  • Article: [Two cystic retroperitoneal lesions mimicking adrenal cysts].
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    ABSTRACT: Adrenal cysts are uncommon lesions and most of them are found incidentally during abdominal imaging. We report on two benign extraadrenal lesions mimicking adrenal tumors in abdominal imaging. The histopathological investigation of the lesions revealed a foregut duplication cyst of the lesser gastric curvature and an epithelial inclusion cyst (epidermoid cyst) in an intrapancreatic accessory spleen respectively.
    Der Pathologe 06/2005; 26(3):226-30. · 0.67 Impact Factor
  • Article: Retroperitoneale Zysten, die Nebennierenzysten imitieren können
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    ABSTRACT: Nebennierenzysten sind selten und werden in der Regel zufllig bei radiologischen Untersuchungen des Abdomens entdeckt. Wir berichten ber zwei extraadrenal gelegene zystische Lsionen, die in der Bildgebung als Nebennierenzysten eingeordnet wurden. Die Untersuchung der Zysten durch die Pathologie ergab die Diagnosen von einerseits einer Duplikaturzyste an der kleinen Magenkurvatur (Kopfdarm) und andererseits einer epithelialen Inklusionszyste der Milz, die sich im vorliegenden Fall wahrscheinlich in eine Nebenmilz am Pankreasschwanz entwickelt hat.Adrenal cysts are uncommon lesions and most of them are found incidentally during abdominal imaging. We report on two benign extraadrenal lesions mimicking adrenal tumors in abdominal imaging. The histopathological investigation of the lesions revealed a foregut duplication cyst of the lesser gastric curvature and an epithelial inclusion cyst (epidermoid cyst) in an intrapancreatic accessory spleen respectively.
    Der Pathologe 04/2005; 26(3):226-230. · 0.67 Impact Factor
  • Article: ETV6-NTRK3 gene fusion in a secretory carcinoma of the breast of a male-to-female transsexual.
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    ABSTRACT: Secretory carcinomas of the breast were first described as "juvenile carcinoma" by McDivitt and Stewart in a cohort of children. This term has been replaced by the term "secretory breast carcinoma", because the entity can occur at any time of life. Carcinoma of the male breast is uncommon and accounts for approximately 1% of all cancers in men. Recently, it has been reported that human secretory breast carcinoma expresses the ETV6-NTRK3 gene fusion that was previously cloned in pediatric mesenchymal cancers. We present the case of a 46-year-old male-to-female transsexual in whom a secretory breast carcinoma was an incidental finding. As confirmation of the histopathological diagnosis we detected the novel ETV6-NTRK3 gene fusion in this tumor.
    The Breast 03/2005; 14(1):71-4. · 2.49 Impact Factor
  • Article: Immunohistochemical differentiation of eosinophilic heart diseases using antibodies against eosinophil activation markers.
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    ABSTRACT: Eosinophilic heart syndromes are rare in Western countries and include endocarditis parietalis fibroplastica (EPF) and hypersensitivity myocarditis (HM). There are striking differences in natural history and morphological findings. Since diagnosis can be difficult when analysing small myocardial biopsies lacking the characteristic histological features, we studied a set of immunohistochemical markers in order to characterize the activation status of the infiltrating eosinophils to distinguish between these two entities. This study is based on the investigation of seven explanted hearts and one left ventricular specimen collected during implantation of a left ventricular assist device from a total of seven patients with HM. Also investigated were three right and three left ventricular specimens from five patients with EPF. We used antibodies (Ab) against EG1, and EG2, CD44, and CD69 which have been described as markers to distinguish between resting and activated eosinophils. The EG1 to EG2 ratio of eosinophils and the immunoreactivity against CD44 showed no differences between the two entities. However, eosinophils in the EPF were completely negative for CD69, whereas eosinophils reacted positively within the HM group. The immunohistochemical investigation of eosinophilic heart diseases using antibodies against CD69 can be a useful tool to distinguish between hypersensitivity myocarditis and endocarditis parietalis fibroplastica.
    Histopathology 02/2005; 46(1):89-97. · 3.08 Impact Factor
  • Article: Vascular anastomosing by gluing--an experimental study.
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    ABSTRACT: Performing anastomoses by stitching is very time-consuming. We therefore looked for an alternative technique and used a relatively new surgical adhesive. Ten anastomoses between the aorta and a prosthesis were performed on five pigs (Deutsche Landrasse) using surgical glue (BioGlue). The proximal anastomoses between the abdominal aorta and the prostheses were performed end-to-side just below the renal arteries, the distal anastomoses in an end-to-end fashion just above the iliac bifurcation. The aorta between the anastomoses was ligated and resected. The animals were sacrificed between one week and up to four months after operation and anastomoses were analysed by angiography, CT angiography, angioscopy, and histology. Angiography and CT angiography revealed that all anastomoses were patent. No aneurysms were found at the site of anastomoses. No haematomas were detected. Angioscopy revealed well-healed connections between the original aorta and the prosthesis. We could demonstrate that anastomoses between the aorta and a prosthesis can be performed safely using a surgical adhesive. Further investigations of these anastomoses, especially over the long term, using calcified aortas, are necessary.
    The Thoracic and Cardiovascular Surgeon 03/2004; 52(1):6-9. · 0.88 Impact Factor
  • Article: [Myocardial alterations with mechanical left ventricular assist devices].
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    ABSTRACT: Left ventricular assist devices (LVAD) have been used to "bridge" patients with end-stage heart failure to transplantation. Although several reports have suggested that the native ventricular function recovers after long-term LVAD support, a process called "reverse remodeling", the underlying biological mechanisms are still unclear. Various molecular pathways of the human myocardium associated with apoptosis, response to stress, or matrix changes are known to be altered under conditions of heart failure, and some have been shown to be reversibly regulated during left ventricular mechanical support, suggesting that the descriptive term "reverse remodeling" is, at least in parts, a reversible mechanism. The reduction of volume and pressure overload with a decrease of ventricular wall stress leading to an improvement of myocardial blood supply under mechanical circulatory assistance, may be one explanation for the molecular myocardial changes and may reflect one possible cause for the phenomenon of "reverse remodeling".
    Der Pathologe 04/2003; 24(2):83-90. · 0.67 Impact Factor
  • Article: Myokardiale Veränderungen unter mechanischer linksventrikulärer Unterstützungstherapie
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    ABSTRACT: Zusammenfassung Linksventrikulre Untersttzungssysteme (LVAD) werden hauptschlich bei terminaler Herzinsuffizienz eingesetzt, um die Wartezeit bis zur Transplantation zu berbrcken. Unter LVAD verbessert sich oftmals die native Herzfunktion, sodass bei einzelnen Patienten das System entfernt werden kann und eine Herztransplantation nicht mehr notwendig ist. Dieser Prozess wird als "reverse remodeling" bezeichnet. Die urschlichen molekularen Mechanismen hierfr sind noch weitgehend unklar. Verschiedene molekulare Systeme spielen bei der Entwicklung der Herzinsuffizienz eine Rolle. Unter LVAD-Therapie werden einzelne dieser System reversibel reguliert. Die Verminderung von Volumen- und Druckbelastung mit einer Abnahme der ventrikulren Wandspannung durch die Entlastungstherapie fhrt neben einer Reduktion der Myozytenhypertrophie auch zu einer verbesserten myokardialen Perfusion und damit zu einer Abnahme der chronischen Ischmie bei Herzinsuffizienz. Diese Verbesserung der myokardialen Durchblutung und Verringerung der ventrikulren Wandspannung wren eine mgliche Erklrung fr die reversible Regulation der beteiligten molekularen Systeme. Abstract Left ventricular assist devices (LVAD) have been used to "bridge" patients with end-stage heart failure to transplantation. Although several reports have suggested that the native ventricular function recovers after long-term LVAD support, a process called "reverse remodeling", the underlying biological mechanisms are still unclear. Various molecular pathways of the human myocardium associated with apoptosis, response to stress, or matrix changes are known to be altered under conditions of heart failure, and some have been shown to be reversibly regulated during left ventricular mechanical support, suggesting that the descriptive term "reverse remodeling" is, at least in parts, a reversible mechanism. The reduction of volume and pressure overload with a decrease of ventricular wall stress leading to an improvement of myocardial blood supply under mechanical circulatory assistance, may be one explanation for the molecular myocardial changes and may reflect one possible cause for the phenomenon of "reverse remodeling".
    Der Pathologe 02/2003; 24(2):83-90. · 0.67 Impact Factor
  • Article: Sudden unexpected death in young adults with chronic hydrocephalus.
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    ABSTRACT: We present four cases of sudden unexpected death in young adults with chronic hydrocephalus. The patients were between 20 and 28 years of age and had suffered from aqueduct stenosis (two patients), spina bifida in combination with Arnold-Chiari malformation (type II) and fragile X-syndrome. The patients suddenly collapsed with cardiorespiratory failure and could not be resuscitated and none had a history of headache or seizures. The post-mortem examinations revealed no unusual findings and a definite cause of death could not be established. Neuropathological examination revealed chronically hydrocephalic brains without any signs of uncal or tonsillar herniation. We hypothesise that a sudden pressure-induced decompensation of cerebral neuronal pathways involving insular and limbic cortex, hypothalamus and brain stem nuclei, may have caused disturbances of the cardiopulmonary control centres in the reticular formation of the brain stem, which in turn may have led to instantaneous cardiorespiratory arrest resulting in sudden "neurogenic" cardiac death.
    Deutsche Zeitschrift für die Gesamte Gerichtliche Medizin 02/2001; 114(6):331-7. · 2.59 Impact Factor

Institutions

  • 2003–2012
    • Universität Duisburg-Essen
      • • Institut für Pathologie und Neuropathologie
      • • Institut für Pathophysiologie
      Duisburg, North Rhine-Westphalia, Germany
    • Universitätsklinikum Essen
      • • Klinik für Unfallchirurgie
      • • Institut für Pathologie und Neuropathologie
      • • Klinik für Kardiologie
      Essen, North Rhine-Westphalia, Germany