F Borchard

Universitätsklinikum Tübingen, Tübingen, Baden-Württemberg, Germany

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Publications (187)508.22 Total impact

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    ABSTRACT: This study examined whether the apoptosis-related protein, BAX, or the microsatellite-instability phenotype provide prognostic information in patients with resected colon cancer. A total of 371 stage I-III patients that previously underwent radical surgery were included (mean follow-up 51.8 months). BAX expression was examined by immunohistochemical staining; high-frequency microsatellite instability (MSI+) was determined by assessing the specific marker, BAT26, using single-strand conformation polymorphism (SSCP)-based analysis. High BAX expression was found in 66.4% of patients. MSI+ tumors were observed in 14.8% of 344 patients. Univariate analysis showed that unlike MSI, low BAX expression was significantly correlated with poor disease-specific overall survival (OS) in stages I-III (p = 0.04). Multivariate subgroup analyses revealed that unlike MSI, low BAX was an independent predictor for OS in stage II (p = 0.009); however, in stages I or III, BAX or MSI were not independent predictors of OS. In stage II colon cancer treated with surgery alone, BAX protein expression may be a predictor for prognosis.
    International Journal of Colorectal Disease 03/2009; 24(6):655-63. · 2.24 Impact Factor
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    ABSTRACT: We evaluated the expression patterns of proapoptotic BAX, antiapoptotic Bcl-2 and p53, the proposed upstream effector of these molecules, as potential prognostic markers in UICC stage III colon cancer by immunohistochemical staining. To identify high-frequency microsatellite instability (MSI+) individuals, we performed single-strand conformation polymorphism-based analysis for BAT26. A total of 188 patients who had received 5-fluorouracil (5-FU)-based adjuvant chemotherapy (5-FU/folinic acid or 5-FU/levamisole) were enrolled. Median follow-up was 84.5 months. We found that BAX, Bcl-2 and p53 protein expressions were high or positive in 59, 70 and 50% of 188 cases, respectively. MSI+ tumours were detected in 9% of 174 evaluable patients. BAX or Bcl-2 was correlated with a higher degree of differentiation or left-sided tumours (P=0.01 or P=0.03, respectively); MSI was correlated with right-sided tumours (P<0.0001). In contrast to p53, Bcl-2, or MSI, low BAX, advanced pN category, low grade of differentiation and treatment with 5-FU/levamisole were univariately associated with poorer disease-free survival (DFS) (P=0.0005, P=0.001, P=0.005 and P=0.01, respectively) and poorer overall survival (OS) (P=0.002, P=0.0001, P=0.003 and P=0.02, respectively). Besides pN category and treatment arm, BAX was an independent variable related to both OS and DFS (P=0.003 and P=0.001, respectively). In both univariate and multivariate analysis, the p53-/BAX high in comparison with the p53+/BAX high subset conferred a significantly improved DFS (P=0.03 and P=0.03, respectively) as well as a marginally improved OS (P=0.07 and P=0.08, respectively). BAX protein expression may be of central significance for clinical outcome to 5-FU-based adjuvant chemotherapy in stage III colon cancer, and bivariate analysis of p53/BAX possibly may provide further prognostic evidence.
    British Journal of Cancer 05/2007; 96(9):1409-18. · 5.08 Impact Factor
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    ABSTRACT: Different histogenetic pathways have been suggested between ulcerative colitis (UC)-associated neoplasia and sporadic colorectal neoplasia. Little is known about the cytokeratin (CK) and mucin expression in UC-associated neoplasms. To clarify the characteristics of UC-associated colorectal carcinogenesis, we examined the immunohistochemical expression of CK7, CK20, MUC2, MUC5AC and MUC6 in 90 colorectal neoplasms, including 22 UC-associated adenocarcinomas (colitic cancer; CC), ten high-grade dysplasias (HGD) in UC, nine low-grade dysplasias (LGD) in UC, 24 sporadic tubular adenomas (TA) and 25 adenocarcinomas (AC). CK7 was positive in most of UC-associated neoplasms: 59% of CC cases, 80% of HGD and 89% of LGD, respectively, whereas, in non-UC associated neoplasia, 21% of TA and 12% of AC. The frequency of MUC6 expression in UC-associated neoplasia was 32% in CC, 30% in HGD and 44% in LGD, respectively, whereas, in non-UC associated neoplasia, 4.2% in TA and 0% in AC. MUC5AC expression in UC-associated neoplasia was detectable in 73% of CC, 90% of HGD and 89% of LGD, respectively; in non-UC associated neoplasia 67% in AC and 20% in TA. There were obvious differences in the expression of CK7 and MUC6 between UC-associated neoplasms and sporadic tumors. The incidence of MUC5AC expression in UC-associated neoplasms was also higher than sporadic tumors. These results suggest that gastric-type mucins play an important role in the initial step of CC-tumorigenesis, and CK7 and gastric-type mucins may be useful in the differential diagnosis between UC-associated neoplasms and sporadic ones.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 07/2006; 448(6):756-62. · 2.68 Impact Factor
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    ABSTRACT: Since 1985, when gastric-type well-differentiated adenocarcinomas were demonstrated in hyperplastic polyps of the stomach, we have studied phenotypic expression in gastrointestinal epithelial lesions. The recent discovery of MUC genes coding core proteins of mucin has improved research on the phenotypic expression of gastrointestinal neoplasms. The disease entity of gastric-type well-differentiated adenocarcinoma has recently been accepted, especially in Japan and Europe. This entity has often become a clinicopathological subject of discussion, because its biological behavior is possibly highly malignant, in spite of the difficulty in making endoscopic and histopathological diagnoses. Even under these circumstances, the term "gastric adenoma" usually means flat adenoma of the intestinal type. Gastric-type adenomas have been regarded as exceptional until recently. Although gastric-type adenomas could theoretically be classified into foveolar type and pyloric-gland type, foveolar-type adenoma is, in practice, difficult to distinguish from gastric-foveolar-type adenocarcinoma. In 2003, we first reported systematic clinicopathological analyses of pyloric gland adenoma, demonstrating its unstable and precancerous nature. In this article, we review and discuss the clinicopathological and molecular pathological aspects of gastric-type well-differentiated adenocarcinomas and pyloric gland adenomas, mainly based on our published and unpublished data.
    Gastric Cancer 02/2006; 9(3):177-84. · 3.99 Impact Factor
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    ABSTRACT: The term "pyloric gland adenoma" reflects its etiogenesis from deep mucoid glands in the stomach. The diagnosis can be confirmed by immunohistochemistry. Typically, pyloric gland adenomas are strongly positive for Mucin 6 (deep mucoid gastric glands). These lesions express Mucin 6 over the whole lesion up to the surface often only with a small layer of columnar epithelium expressing Apomucin 5AC. The amount of mucin 5AC which is expressed on normal within the apical foveolar epithelium might vary from case to case. Combination or transdifferentiation with ordinary tubular (intestinal differentiation) adenoma can be observed. The gastric corpus mucosa of elderly female patients with autoimmune gastritis is highly affected. The frequency of pyloric gland adenoma is given in the literature being 2.7% of all gastric polyps. Therefore pyloric gland adenomas are not that rare that one might assume. Only a few publications are available which makes one think that these lesions are frequently misinterpreted. Pyloric gland adenomas can arise in gastric heterotopia and gastric metaplasia in the whole gastrointestinal tract. The clinical significance is given by a 30% rate of malignant transformation. These cases represent for the most well differentiated early adenocarcinomas which are known to have an excellent prognosis after complete polypectomy and limitation to the mucosal layer.
    Ceskoslovenska patologie 02/2006; 42(1):4-7.
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    ABSTRACT: Pyloric gland adenoma is a recently described and very rare entity. The occurrence of adenoma is very unusual in Barrett's epithelium of the esophagus. We report a case of esophageal polyp showing the features of pyloric gland adenoma, which was surrounded by so-called specialized columnar epithelium. Immunohistochemically, most tumor glands were strongly positive for MUC6, except in the superficial layer. MUC5AC was positive in almost all tumor cells, but MUC2 and CD10 were negative in the tumor. MIB-1-positive proliferating cells were distributed throughout the tumor. Microdissection and comparative genomic hybridization analyses revealed losses on 2p24-25.2, 2q14.1-ter, 5q31.3-32, 6q23-24, 8q23-24.2, 11q22.3-24 and 18q21.1-22. This is the first case of pyloric gland adenoma found to arise in Barrett's epithelium of the esophagus, showing its unstable and precancerous nature.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 06/2005; 446(5):537-41. · 2.68 Impact Factor
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    ABSTRACT: In a 46-year-old man, a pedunculated rectal polyp measuring 3.0x3.0x2.0 cm was diagnosed histologically as a pyloric gland-type adenoma arising in heterotopic gastric corpus mucosa. The luminal site was covered by glands of the gastric foveolar type, displaying focal marked proliferation interpreted as low-grade intraepithelial neoplasia. A bidirectional gastric differentiation was found: most lower glandular structures showed positivity for the deep gastric mucin core protein Muc 6 and superficial positivity for gastric foveolar epithelium mucin core protein Muc 5AC. Pyloric gland adenoma has so far been described in one larger series only and a few case reports of the stomach, gallbladder, pancreatic duct and within heterotopic gastric corpus mucosa of the duodenal bulb. The present case report is the first case of a pyloric gland-type adenoma within a gastric corpus heterotopia of the rectal mucosa.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 06/2005; 446(5):542-5. · 2.68 Impact Factor
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    ABSTRACT: To determine the prognostic impact of BAX in correlation to its upstream effector p53 as well as clinicopathologic variables and patient outcome in preoperatively irradiated rectal carcinoma. We investigated 92 rectal carcinoma patients treated by preoperative radiotherapy to a total dose of 30 Gy followed by surgery. Median follow-up was 71 months. Immunohistochemistry was performed on paraffin sections of pretreatment biopsy samples for BAX protein. Also, we considered the previously determined p53 expression data from this cohort. BAX protein expression was classified as high and low in 63 (68.5%) and 29 (31.5%) tumors, respectively. Unlike clinicopathologic variables, high BAX expression was significantly associated with improved disease-free survival by univariate analysis (p = 0.048). Moreover, in multivariate analyses, high BAX expression was an independent prognostic indicator for both improved local recurrence-free interval and improved disease-free survival (p = 0.03 and 0.047, respectively). Concerning the p53/BAX pathway, subgroup analysis yielded no association between p53 immunonegative/BAX high vs. p53 immunopositive/BAX low expressing tumors with regard to overall, disease-free, or local recurrence-free survival in either univariate (p = 0.88, 0.54, and 0.16, respectively) or multivariate analysis. This study demonstrates that BAX protein expression might help to predict disease recurrence in preoperatively irradiated rectal carcinoma, whereas determination of p53, the proposed upstream regulator of BAX-induced apoptosis, did not provide additional prognostic information.
    International Journal of Radiation OncologyBiologyPhysics 02/2005; 61(1):85-91. · 4.52 Impact Factor
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    ABSTRACT: In the Dukes' B and C stages of colorectal carcinoma there are considerable variations in the observed courses of the disease. Since post-operative chemotherapy in patients with Dukes' C (node-positive) colon carcinoma has been demonstrated to be effective in improving overall-survival, a more exact prognosis assessment gains additional significance and therapeutic relevance. One also hopes to derive improved prognostic factors from the clarification of the molecular pathogenesis. Because of its frequency and the accessibility and recognizability of its developmental stages colorectal carcinoma is among the best investigated of all solid tumors. Despite a multitude of suggested molecular candidate markers none of these changes has yet been able enter the everyday life of the clinic. However, it is to be expected that some of the molecular alterations presently discussed will gain importance before long in the clinical treatment of patients with colorectal carcinoma. Considering also our own findings, this review presents the latest developments in the scientific discussion of the tumor suppressor/oncogenes p53, k-ras, and DCC, biochemical determinants of the 5-fluorouracil metabolism, and defects of the DNA repair system.
    International Journal of Colorectal Disease 02/2004; 19(1):23-42. · 2.24 Impact Factor
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    ABSTRACT: There are a number of difficulties regarding the diagnosis of Barrett's mucosa and the varying grades of neoplasia that may be associated with it. It was, therefore, the aim of a consensus conference of the Working Group for Gastroenterological Pathology within the German Society of Pathology to achieve standardisation regarding the following issues: definition and diagnostic criteria for Barrett's mucosa and its discrimination from intestinal metaplasia of the cardia, diagnostic criteria for intraepithelial neoplasia, number of biopsies necessary to establish the diagnosis, significance of additional immunohistochemical and/or molecular methods as well as importance of a second opinion in the diagnosis of intraepithelial neoplasia.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 12/2003; 443(5):597-601. · 2.68 Impact Factor
  • M Vieth, R Kushima, F Borchard, M Stolte
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    ABSTRACT: Pyloric gland adenoma is a rarely described neoplasia of the gastric mucosa. Recent publications have shown that similar lesions are also found in the gallbladder, the main pancreatic duct, the duodenum and the cervix of the uterus. Apart from case reports, few clinical data are available on these patients. We therefore conducted a search of the archived material collected between 1990 and 2000 for more clinical data on patients with this rare lesion. Between 1990 and 2000, 90 patients were diagnosed as having a pyloric gland adenoma in the stomach (77 patients), duodenal bulb (7 patients), duodenum (1 patient), bile duct (3 patients) or gallbladder (2 patients). Pyloric gland adenomas account for 2.7% of all gastric polyps and occur predominantly in old age (73+/-12.8 years), more frequently in women (75%) than in men. The predilection site in the stomach is the corpus mucosa (64%) and they are often found in patients suffering from autoimmune gastritis (36%). At the time of diagnosis, pyloric gland adenomas measure 16.1+/-9.1 mm in size. In 30% of gastric pyloric adenomas, transition to well-differentiated adenocarcinoma has been noted. In our material, pyloric gland adenoma is the third most common neoplastic polypoid lesion in the stomach. Since a search through the literature revealed only a few case reports on this lesion, it is possible that for some reason this lesion might be diagnosed more often than reported. Our study revealed that 30% of the gastric pyloric gland adenomas showed continuous transition to well-differentiated adenocarcinoma at the time of the initial diagnosis. This underscores the malignant potential of the lesion, and the need for polypectomy.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 05/2003; 442(4):317-21. · 2.68 Impact Factor
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    ABSTRACT: There are a number of difficulties regarding the diagnosis of Barrett's mucosa and the varying grades of neoplasia that may be associated with it. It was therefore the aim of a consensus conference of the "Working Group for Gastroenterological Pathology within the German Society of Pathology" to achieve standardization regarding the following issues: definition and diagnostic criteria for Barrett's mucosa and its discrimination from intestinal metaplasia of the cardia, diagnostic criteria for intraepithelial neoplasia, number of biopsies necessary to establish the diagnosis, significance of additional immunohistochemical and/or molecular biological methods as well as importance of a second opinion in the diagnosis of intraepithelial neoplasia.
    Der Pathologe 03/2003; 24(1):9-14. · 0.62 Impact Factor
  • Gastroenterology 01/2003; 124(4). · 12.82 Impact Factor
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    ABSTRACT: We report a case of a pedunculated polyp with a focus of gastric-type adenocarcinoma arising in the opposite side of the papilla Vater of the duodenal second portion. The carcinoma was surrounded by lobules of hyperplastic Brunner's glands. Immunohistochemically the carcinoma tissue showed both gastric foveolar-type mucin ( MUC5AC) and pyloric/Brunner's gland-type mucin ( MUC6), in which proliferating cells positive for MIB-1 (Ki-67) were scattered diffusely. Most of the hyperplastic Brunner's glands were positive for MUC6, while cells toward the lumen in the superficial layer were positive for MUC5AC and MIB-1. This directional pattern of differentiation of Brunner's glands has recently been demonstrated by our group in the histogenetic course of gastric metaplasia originating directly from Brunner's glands. Therefore the present carcinoma is thought to have developed under induction of gastric-foveolar differentiation in a manner very similar to that of gastric metaplasia in hyperplastic Brunner's glands.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 07/2002; 440(6):655-9. · 2.68 Impact Factor
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    ABSTRACT: We evaluate the usefulness of screening for p53 and Ki-ras mutations in comparison with histological and flow cytometric findings. We analyzed 1486 biopsy samples from 769 locations of 83 patients with long-standing ulcerative colitis enrolled in a surveillance program by means of histology, flow cytometry and SSCP analysis. As a control we used 66 biopsy samples of 16 patients with irritable bowel disease. With respect to all biopsy samples analyzed, DNA aneuploidy was found in 32.5% (27/83) of patients, dysplasia in 22.9% (15/83), p53 in 21.7% (18/83) and Ki-ras mutations in 18.1% (15/83) of patients. None of these markers was found in our control group. In 7 out of 10 patients who displayed dysplastic findings during endoscopic surveillance p53 and / or Ki-ras mutations were present in at least one colonoscopy. Statistically significant associations were observed between dysplasia and DNA aneuploidy (P < 0.001), between dysplasia and p53 mutations (P = 0.05) and between dysplasia and p53 and/or Ki-ras mutations (P = 0.002). No significant associations were found between dysplasia and Ki-ras mutations alone. The results for the SSCP analysis showed a much broader variation than those for the flow cytometric analysis. These results show that screening for p53 and Ki-ras mutations can be a useful adjunct in surveillance of patients with long-standing ulcerative colitis.
    Scandinavian Journal of Gastroenterology 01/2002; 36(12):1320-6. · 2.33 Impact Factor
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    ABSTRACT: Patients with ulcerative colitis (UC) are prone to develop colorectal cancer which is related to the duration and extent of the disease. One of the earliest events in tumor progression is the development of aneuploidy. Aneuploidy is correlated with the grade of dysplasia which serves as a common but not always reproducible marker for the prediction of UC associated formation of cancer. We analyzed 48 biopsy samples from 5 patients with long-standing ulcerative colitis by comparative genomic hybridization (CGH). The majority of these samples represented premalignant stages which are not well characterized at the molecular level as yet. We compared biopsy samples from different colon locations in regard to chromosomal alterations, dysplasia status and DNA index. Besides chromosomal changes occurring only in certain patients in restricted areas of the colon we also detected amplifications and deletions which were common in all persons throughout the colon. The stage of dysplasia seems to have no influence on the number and appearance of chromosomal changes. Amplifications in 2, 3, 6, 9, 11, 12 and 15 were found in almost all cases. In dysplastic samples chromosomal regions 3, 6 and 11 revealed gains of DNA. Deletions were detected within 8q, 15, 18q, 20p and 22q. The affected chromosomal regions may contain yet unknown oncogenes or tumor suppressor genes participating in UC associated carcinogenesis. The conspicuous regions found in the CGH experiments allow the selective and detailed characterization at a molecular level.
    International Journal of Oncology 10/2001; 19(3):489-94. · 2.66 Impact Factor
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    ABSTRACT: To examine the prevalence of DNA aneuploidy as a function of the extent of ulcerative colitis and to study the correlation of aneuploidy with clinical characteristics. Furthermore, the occurrence of aneuploidy and dysplasia during colonoscopic surveillance was studied in a subset of these patients. By analyzing 5404 biopsy samples of 368 patients with ulcerative colitis, we have evaluated the importance of DNA ploidy measured by flow cytometry. We have also investigated the influence of extent (219 patients with extensive or total colitis vs. 149 patients with localized colitis) and duration of colitis on the development of dysplasia (patients with biopsy specimens that showed inflammation alone were compared with those with biopsy specimens that were equivocal or positive for dysplasia) and aneuploidy. Included was a subgroup of patients with ulcerative colitis and primary sclerosing cholangitis (n = 16). Aneuploidy was found in 8.7 percent (32/368) of all patients. The prevalence of aneuploidy increased by the extent of ulcerative colitis (2 percent localized, 6.8 percent extensive colitis, 14.9 percent total colitis). The frequency of aneuploidy was higher in patients with disease duration longer than 10 years (P = 0.007). Patients with ulcerative colitis and primary sclerosing cholangitis were more likely to develop aneuploidy (9/16, 56.3 percent vs. 14/120, 11.7 percent; P < 0.001) and dysplasia (4/16, 25 percent vs. 10/120, 8.3 percent; P = 0.06) than patients without primary sclerosing cholangitis. Because DNA aneuploidy represents an early alteration during neoplastic transformation in ulcerative colitis, flow cytometry is a valuable tool in the surveillance of those patients. Primary sclerosing cholangitis represents an additional risk factor for the development of DNA aneuploidy and dysplasia.
    Diseases of the Colon & Rectum 10/2001; 44(10):1446-55. · 3.34 Impact Factor
  • Gastroenterology 04/2001; 120(5). · 12.82 Impact Factor
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    ABSTRACT: The diagnosis of celiac disease (CD) is based upon histological findings in duodenal or jejunal biopsies. In the past few years it has turned out that the development of CD lesion in the small bowel is a dynamic process which may present in various histological forms. At one end of the spectrum is a mucosa with normal architecture and an increase in intraepithelial lymphocytes (IEL), at the other end is the classical flat mucosa. Histological features supporting the diagnosis of CD are architectural changes of the villi and/or crypts, an increase in lamina propria cell density and an increase in IEL counts. For diagnostic purposes and for monitoring of CD patients an exact histological classification of the histological findings has to be given. This has become possible by using a modified Marsh classification. In the present paper the histological presentation of CD is presented as well as the modified Marsh classification and the most important differential diagnoses.
    Zeitschrift für Gastroenterologie 03/2001; 39(2):157-66. · 1.41 Impact Factor
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    ABSTRACT: The diagnosis of celiac disease (CD) is based upon histological findings in duodenal or jejunal biopsy specimens. In recent years it has been seen that the development of CD lesion in the small bowel is a dynamic process which may present in various histological forms. At one end of the spectrum is a mucosa with normal architecture and an increase in intraepithelial lymphocytes; at the other end is the classical flat mucosa. Histological features supporting the diagnosis of CD are architectural changes of the villi and/or crypts, an increase in lamina propria cell density, and an increase in intraepithelial lymphocytes counts. Exact histological classification of the histological findings is required for diagnostic purposes and for monitoring of CD patients. This has become possible by using a modified Marsh classification. We present both the histological presentation of CD and the modified Marsh classification, and the most important differential diagnoses.
    Der Pathologe 02/2001; 22(1):72-81. · 0.62 Impact Factor

Publication Stats

4k Citations
508.22 Total Impact Points

Institutions

  • 1999–2009
    • Universitätsklinikum Tübingen
      Tübingen, Baden-Württemberg, Germany
  • 2006
    • Kyoto Prefectural University of Medicine
      • Graduate School of Medical Science
      Kioto, Kyōto, Japan
  • 2005–2006
    • University of Bayreuth
      Bayreuth, Bavaria, Germany
  • 1996–2006
    • Shiga University of Medical Science
      • • Department of Pathology
      • • Department of Clinical Laboratory Medicine
      Ōtu, Shiga, Japan
  • 1997–2005
    • University of Tuebingen
      • Department of Internal Medicine
      Tübingen, Baden-Wuerttemberg, Germany
    • Friedrich-Alexander Universität Erlangen-Nürnberg
      Erlangen, Bavaria, Germany
  • 2003
    • Otto-von-Guericke-Universität Magdeburg
      • Institute for Pathology
      Magdeburg, Saxony-Anhalt, Germany
  • 2001
    • University of Vienna
      Wien, Vienna, Austria
  • 2000–2001
    • Virginia Commonwealth University
      • Department of Radiation Oncology
      Richmond, VA, United States
  • 1974–1998
    • Heinrich-Heine-Universität Düsseldorf
      • • Klinik für Gastroenterologie, Hepatologie und Infektiologie
      • • Institute of Neuropathology
      • • Medizinische Fakultät
      • • Nuklearmedizinische Klinik
      Düsseldorf, North Rhine-Westphalia, Germany
  • 1989
    • Medizinische Laboratorien Düsseldorf
      Düsseldorf, North Rhine-Westphalia, Germany
  • 1988
    • Ludwig-Maximilian-University of Munich
      • Institut für Tierpathologie
      München, Bavaria, Germany