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4. Entwicklung eines dreidimensionalen Prostatakarzinomzellkulturmodells

Author

Jung, V., Saar, M., Grobholz, R., Stöckle, M., Unteregger, G., and Kamradt, J.

Abstract

Zusammenfassung: Zahlreiche Erkenntnisse in der Prostatakarzinomforschung basieren auf Zellkulturergebnissen. Neuere genomische Untersuchungen zeigen jedoch, dass verwendete permanente Prostatakarzinomzelllinien sich deutlich von dem klinisch relevanten, primären Prostatakarzinom unterscheiden und damit die Übertragbarkeit dieser Zellkulturergebnisse auf die Klinik nur bedingt gegeben ist. Das Arbeiten mit Primärzellkulturen aus Gewebestückchen von Prostatektomiepräparaten bietet eine sehr gute Alternative, doch die Etablierung von Primärkulturen gestaltet sich schwierig und recht aufwändig. In dieser Arbeit wurde ein Primärzellkulturmodell mit einem Invasionssystem kombiniert. Hiermit gelang es nicht nur invasiv wachsende Zellpopulationen aus Primärkulturen zu selektionieren, sondern auch diese Zellen in einem 3D-Modell unter der Ausbildung von Sphäroiden weiter zu kultivieren. Zur Charakterisierung dieser Zellpopulation haben wir vergleichende genomische Hybridisierungen durchgeführt, die zahlreiche genetische Alterationen aufzeigen. Das hier dargestellte Modell ermöglicht es erstmalig, invasive Zellklone aus primärem Prostatakarzinomgewebe zu gewinnen und durch Kultivierung für weitere Untersuchungen zu verwenden.

Published
2024
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6. Beteiligung von VEGF-R (vascular endothelial growth factor receptor) und NGF (nerve growth factor) bei der Neovaskularisation als Ursache der Rezidivvarikosis in der Krosse

Author

Rewerk, S., Meyer, A. J., Duczek, C., Winkler, M., Nüllen, H., Grobholz, R., Willeke, F., Bruch, H. P., editor, Büchler, M. W., editor, Buhr, H. J., editor, Hohenberger, W., editor, Klar, E., editor, Kremer, B., editor, Post, S., editor, Schilling, M., editor, Schumpelick, V., editor, Siewert, J. R., editor, Thiede, A., editor, Becker, H., editor, Bittner, R., editor, Függer, R., editor, Köckerling, F., editor, Saeger, H. D., editor, Zornig, C., editor, Hölscher, A., editor, Izbicki, J. R., editor, Junginger, T., editor, Senninger, N., editor, Allgayer, H., editor, Broll, R., editor, Bruns, C. J., editor, Fries, H., editor, Kalthoff, H., editor, Schackert, H. K., editor, Ertel, W., editor, Faist, E., editor, Holzheimer, R. G., editor, Holzmann, B., editor, Schade, U. F., editor, Vollmar, B., editor, Brückner, U. B., editor, Heidecke, C. D., editor, Menger, M. D., editor, Neugebauer, E., editor, Spiegel, H. U., editor, Biemer, E., editor, Germann, G., editor, Haas, N., editor, Machens, H. G., editor, Stark, G. B., editor, Steinau, H. U., editor, Haverich, A., editor, Heberer, M., editor, Rogiers, X., editor, Jauch, K. W., editor, Roth, H., editor, von Schweinitz, D., editor, Waag, K. L., editor, Altendorf-Hofmann, A., editor, Celik, I., editor, Lehnert, T., editor, Lorenz, W., editor, Ohmann, C., editor, Bechstein, W. O., editor, Broelsch, C., editor, Hopt, U., editor, Klempnauer, J., editor, Neuhaus, P., editor, Fändrich, F., editor, Markus, B., editor, Minor, T., editor, Wonigeit, K., editor, Dralle, H., editor, Goretzki, P. E., editor, Rothmund, M., editor, Bühren, V., editor, Josten, C., editor, Muhr, G., editor, Nast-Kolb, D., editor, Stürmer, K. M., editor, Trentz, O., editor, Brunkwall, J., editor, Sandmann, W., editor, Schmitz-Rixen, T., editor, Storck, M., editor, Branscheid, D., editor, Dienemann, H., editor, Hirner, A., editor, Passlick, B., editor, Toomes, H., editor, Beyersdorf, F., editor, Hetzer, R., editor, Schäfers, H. J., editor, Zerkowski, H. R., editor, Becker, H. D., editor, Saeger, H. -D., editor, Jauch, K. -W., editor, and Bauer, H., editor

Published
2006
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13. Digitale Pathologie

Author

Grobholz R

Subjects
0301 basic medicine, Multimedia, Point (typography), Computer science, Process (engineering), Digital pathology, Tissue reconstruction, Routine practice, computer.software_genre, Pathology and Forensic Medicine, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Workflow, 030220 oncology & carcinogenesis, Digital image analysis, computer, Desk
Abstract

Background Digital pathology (DP) and whole-slide imaging (WSI) technology have matured substantially over the last few years. Meanwhile, commercial systems are available that can be used in routine practice. Aims Illustration of DP experiences in a routine diagnostic setting. Results and conclusions A DP system offers several advantages: 1) glass slides are no longer unique; 2) access to cases is possible from any location; 3) digital image analysis can be applied; and 4) archived WSI can be easily accessed. From this point, several secondary advantages arise: a) the slide compilation of the case and the case assignment is fast and safe; b) carrying cases to the pathologist is obsolete and paperless work is possible; c) WSI can be used for a second opinion and be accessible in remote locations; d) WSI of referred cases are still accessible after returning the slides; e) histological images can easily be provided in tumor boards; f) the office desk is clean; and g) a "home office" is possible. To introduce a DP system, a comprehensive workflow analysis is needed that clarifies the needs and wishes of the respective institute. In order to optimally meet the requirements, open DP platforms are of particular advantage, because they enable the integration of scanners from various manufacturers. Further developments in image analysis, such as virtual tissue reconstruction, could enrich the diagnostic process in the future and improve treatment quality.

Published
2018

25. Coronary Heart Disease and an Incidental Parathyroid Carcinoma

Author

Stoll, M., Nebiker, C. A., Remonda, L., and Grobholz, R.

Subjects
Article Subject
Abstract

A 71-year-old woman was admitted with angina pectoris. During hospitalization she developed a myocardial infarction (NSTEMI). Laboratory results revealed a mild elevated troponin and an elevated calcium level (3.35 mmol/l). Subsequently, there was a decreased phosphate (0.36 mmol/l [normal 0.81-1.62 mmol/l]) as well as 16-fold elevated serum level of parathyroid hormone (PTH, 1156 ng/l [normal 10-73 ng/l]), indicating a primary hyperparathyroidism. Sonographically a thyroidal node was detected, not clearly demarcated (TIRADS 5). FNA showed a monomorphic, partial follicular cell population with an immunohistochemical positivity for PTH. Magnetic resonance imaging (MRI) showed a 5 cm large tumor at the right caudal pole of the thyroid with compression of the dorsolateral trachea without infiltration. Surgical removal with en bloc resection of the right hemithyroid with parathyroidectomy was performed. Postoperatively the PTH level dropped to 12.1 ng/l. Pathological examination revealed a 5 cm tumor with infiltration of the thyroid and a perineural invasion. The diagnosis of a presymptomatic parathyroid carcinoma could be established. The affirmative histopathological diagnosis of a parathyroid carcinoma can be challenging and is limited to tumors with evidence of invasive growth in adjacent structures such as the thyroid and/or soft tissue, perineural spaces, angioinvasion of capsular and/or extracapsular vessels, and/or documented metastases.

Published
2019
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32. Akute Lidschwellung

Author

B. Röhrl, Christoph Düber, Maliha Sadick, Hahn S, Hörmann K, and Grobholz R

Subjects
medicine.medical_specialty, Text mining, business.industry, medicine, Radiology, Nuclear Medicine and imaging, Swelling, medicine.symptom, business, Dermatology
Published
2006

33. Intraductal carcinoma of prostate reporting practice: a survey of expert European uropathologists

Author

Varma, M., Egevad, L., Algaba, F., Berney, D., Bubendorf, L., Camparo, P., Comperat, E., Erbersdobler, A., Griffiths, D., Grobholz, R., Haitel, A., Hulsbergen-van de Kaa, C.A., Langner, C., Loftus, B., Lopez-Beltran, A., Mayer, N., Nesi, G., Oliveira, P., Oxley, J., Rioux-Leclercq, N., Seitz, G., Shanks, J., Kristiansen, G., Varma, M., Egevad, L., Algaba, F., Berney, D., Bubendorf, L., Camparo, P., Comperat, E., Erbersdobler, A., Griffiths, D., Grobholz, R., Haitel, A., Hulsbergen-van de Kaa, C.A., Langner, C., Loftus, B., Lopez-Beltran, A., Mayer, N., Nesi, G., Oliveira, P., Oxley, J., Rioux-Leclercq, N., Seitz, G., Shanks, J., and Kristiansen, G.

Abstract

Item does not contain fulltext, BACKGROUND: It is unclear whether the reported variation in the diagnosis of intraductal carcinoma of the prostate (IDC-P) is due to variable interpretation of borderline morphology, use of different diagnostic criteria or both. AIMS: We sought to determine the degree of variation in the diagnostic criteria and reporting rules for IDC-P in prostate biopsies employed by expert uropathologists. METHODS: A questionnaire survey was circulated to 23 expert uropathologists from 11 European countries. RESULTS: Criteria used for diagnosis of IDC-P included solid intraductal growth (100%), dense cribriform (96%), loose cribriform/micropapillary with nuclear size >6x normal (83%) or comedonecrosis (74%) and dilated ducts >2x normal (39%). 'Nuclear size' was interpreted as nuclear area by 74% and nuclear diameter by 21%. Pure IDC-P in needle biopsies was reported by 100% and Gleason graded by 30%. All would perform immunohistochemistry in such cases to rule out invasive cancer. An IDC-P component associated with invasive cancer would be included in the determination of tumour extent and number of cores involved by 74% and 83%, respectively. 52% would include IDC-P component when grading invasive cancer. 48% would perform immunohistochemistry in solid or cribriform nests with comedonecrosis to exclude IDC-P (17% routinely, 30% if the focus appeared to have basal cells on H&E). 48% graded such foci as Gleason pattern 5 even if immunohistochemistry demonstrated the presence of basal cells. CONCLUSIONS: There is a need for more clarity in the definition of some of the diagnostic criteria for IDC-P as well as for greater standardisation of IDC-P reporting.

Published
2016

34. New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs

Author

Sturm, D., Orr, B.A., Toprak, U.H., Hovestadt, V., Jones, D.T., Capper, D., Sill, M., Buchhalter, I., Northcott, P.A., Leis, I., Ryzhova, M., Koelsche, C., Pfaff, E., Allen, S.J., Balasubramanian, G., Worst, B.C., Pajtler, K.W., Brabetz, S., Johann, P.D., Sahm, F., Reimand, J., Mackay, A., Carvalho, D.M., Remke, M., Phillips, J.J., Perry, A., Cowdrey, C., Drissi, R., Fouladi, M., Giangaspero, F., Lastowska, M., Grajkowska, W., Scheurlen, W., Pietsch, T., Hagel, C., Gojo, J., Lotsch, D., Berger, W., Slavc, I., Haberler, C., Jouvet, A., Holm, S., Hofer, S., Prinz, M., Keohane, C., Fried, I., Mawrin, C., Scheie, D., Mobley, B.C., Schniederjan, M.J., Santi, M., Buccoliero, A.M., Dahiya, S., Kramm, C.M., Bueren, A.O. von, Hoff, K. von, Rutkowski, S., Herold-Mende, C., Fruhwald, M.C., Milde, T., Hasselblatt, M., Wesseling, P., Rossler, J., Schuller, U., Ebinger, M., Schittenhelm, J., Frank, S., Grobholz, R., Vajtai, I., Hans, V., Schneppenheim, R., Zitterbart, K., Collins, V.P., Aronica, E., Varlet, P., Puget, S., Dufour, C., Grill, J., Figarella-Branger, D., Wolter, M., Schuhmann, M.U., Shalaby, T., Grotzer, M., Meter, T. van, Monoranu, C.M., Felsberg, J., Reifenberger, G., Snuderl, M., Forrester, L.A., Koster, J., Versteeg, R., Volckmann, R., Sluis, P. van, Wolf, S., Mikkelsen, T., Gajjar, A., Aldape, K., Moore, A.S., Taylor, M.D., Jones, C., et al., Sturm, D., Orr, B.A., Toprak, U.H., Hovestadt, V., Jones, D.T., Capper, D., Sill, M., Buchhalter, I., Northcott, P.A., Leis, I., Ryzhova, M., Koelsche, C., Pfaff, E., Allen, S.J., Balasubramanian, G., Worst, B.C., Pajtler, K.W., Brabetz, S., Johann, P.D., Sahm, F., Reimand, J., Mackay, A., Carvalho, D.M., Remke, M., Phillips, J.J., Perry, A., Cowdrey, C., Drissi, R., Fouladi, M., Giangaspero, F., Lastowska, M., Grajkowska, W., Scheurlen, W., Pietsch, T., Hagel, C., Gojo, J., Lotsch, D., Berger, W., Slavc, I., Haberler, C., Jouvet, A., Holm, S., Hofer, S., Prinz, M., Keohane, C., Fried, I., Mawrin, C., Scheie, D., Mobley, B.C., Schniederjan, M.J., Santi, M., Buccoliero, A.M., Dahiya, S., Kramm, C.M., Bueren, A.O. von, Hoff, K. von, Rutkowski, S., Herold-Mende, C., Fruhwald, M.C., Milde, T., Hasselblatt, M., Wesseling, P., Rossler, J., Schuller, U., Ebinger, M., Schittenhelm, J., Frank, S., Grobholz, R., Vajtai, I., Hans, V., Schneppenheim, R., Zitterbart, K., Collins, V.P., Aronica, E., Varlet, P., Puget, S., Dufour, C., Grill, J., Figarella-Branger, D., Wolter, M., Schuhmann, M.U., Shalaby, T., Grotzer, M., Meter, T. van, Monoranu, C.M., Felsberg, J., Reifenberger, G., Snuderl, M., Forrester, L.A., Koster, J., Versteeg, R., Volckmann, R., Sluis, P. van, Wolf, S., Mikkelsen, T., Gajjar, A., Aldape, K., Moore, A.S., Taylor, M.D., Jones, C., and et al.

Abstract

Item does not contain fulltext, Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs, we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated "CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)," "CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)," "CNS high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1)," and "CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR)," will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by poorly differentiated CNS tumors.

Published
2016

36. Mimikry eines Leberabszesses als hepatozelluläres Karzinom

Author

Grobholz R, Kilian Ak, Prosst Rl, and Post S

Subjects
medicine.medical_specialty, Cirrhosis, business.industry, medicine.medical_treatment, General Medicine, Gallstones, medicine.disease, medicine.anatomical_structure, Hepatocellular carcinoma, Laparotomy, Medicine, Abdomen, Cholecystectomy, Radiology, business, Abscess, Liver abscess
Abstract

HISTORY: We report on a 82 year-old male who presented with chronic pain in the right upper abdomen, nausea and vomitus. An uncomplicated laparoscopic cholecystectomy occurred eight years and a hepatitis 60 years before. Clinical examination showed a normal abdominal status without palpable liver, spleen, enlarged lymph nodes or masses. He had no icteric skin and sclera. INVESTIGATIONS: The patient was afebrile without leukocytosis. The tumour markers CEA, CA 19 - 9 and AFP were negative. Ultrasound of the abdomen showed a normal homogeneous echotexture of the liver without signs of cholestasis or cirrhosis. In segment 6 a 3 cm large hypoechoic cystic formation with a central echogenic structure with acoustic shadowing was noted. Magnetic resonance revealed a 2.8 x 3.6 cm large lesion in the dorsal region of segment 6 of the liver, infiltrating the perihepatic fat. Pathologic lymph nodes and metastases were not found. DIAGNOSIS AND TREATMENT: At laparotomy, the tumour appeared to be malignant with invasion to the perirenal fat. Complete resection with negative margins included segment 6 of the liver and the adjacent fat (the kidney itself was not infiltrated). The cut specimen also showed signs of malignancy with central necrosis. However, histology of the resected specimen revealed a sterile liver abscess without malignancy, but with microscopic foreign bodies. The patient had an uneventful recovery without postoperative complications. CONCLUSIONS: This case report demonstrates the difficulty encountered in the differential diagnosis of inflammatory processes and malignant tumours. Chronic inflammatory changes may mimic solid neoplasms. Despite adequate magnetic resonance imaging and thorough intraoperative examination, the correct diagnosis was finally found by histology. The most likely genesis of the abscess are lost gallstones during cholecystectomy.

Published
2003

39. Standardization of Gleason grading among 337 European pathologists

Author

Egevad, L, Ahmad, AS, Algaba, F, Berney, DM, Boccon-Gibod, L, Comperat, E, Evans, AJ, Griffiths, D, Grobholz, R, Kristiansen, G, Langner, C, Lopez-Beltran, A, Montironi, R, Moss, S, Oliveira, P, Vainer, B, Varma, M, and Camparo, P

Subjects
Gleason grading, male, biopsy, pathology, human, reproducibility, prostatic neoplasms
Abstract

Egevad L, Ahmad A S, Algaba F, Berney D M, Boccon-Gibod L, Comperat E, Evans A J, Griffiths D, Grobholz R, Kristiansen G, Langner C, Lopez-Beltran A, Montironi R, Moss S, Oliveira P, Vainer B, Varma M & Camparo P (2013) Histopathology 62, 247-256 Standardization of Gleason grading among 337 European pathologists Aims: The 2005 International Society of Urological Pathology (ISUP) modification of Gleason grading recommended that the highest grade should always be included in the Gleason score (GS) in prostate biopsies. We analysed the impact of this recommendation on reporting of GS 6 versus 7. Methods and results: Fifteen expert uropathologists reached two-thirds consensus on 15 prostate biopsies with GS 67 cancer. Eighty-five microphotographs were graded by 337 of 617 members of the European Network of Uropathology (ENUP), representing 19 countries. There was agreement between expert and majority member GS in 12 of 15 cases, while members upgraded in three cases. Among members and the expert consensus, a GS >6 was assigned by 64.5% and 60%, respectively. Mean member GS was higher than consensus GS in nine of 15 cases. A Gleason pattern (GP) 5 was reported by 0.35.6% in 10 cases. Agreement between consensus and member GS was 58.289.3% (mean 71.4%) in GS 6 cases and 46.363.8% (mean 56.4%) in GS 7 cases (P = 0.009). Conclusions: While undergrading of prostate cancer used to be prevalent, some now tend to overgrade. Minimum diagnostic criteria for GP 4 and 5 in biopsies need to be better defined. Image libraries reviewed by experts may be useful for standardization.

Published
2013

40. Utility of whole slide imaging and virtual microscopy in prostate pathology

Author

Camparo, P, Egevad, L, Algaba, F, Berney, DM, Boccon-Gibod, L, Comperat, E, Evans, AJ, Grobholz, R, Kristiansen, G, Langner, C, Lopez-Beltran, A, Montironi, R, Oliveira, P, Vainer, B, and Varma, M

Subjects
prostate, whole slide images, expert analysis, Telepathology, virtual microscopy
Abstract

Whole slide imaging (WSI) has been used in conjunction with virtual microscopy (VM) for training or proficiency testing purposes, multicentre research, remote frozen section diagnosis and to seek specialist second opinion in a number of organ systems. The feasibility of using WSI/VM for routine surgical pathology reporting has also been explored. In this review, we discuss the utility and limitations of WSI/VM technology in the histological assessment of specimens from the prostate. Features of WSI/VM that are particularly well suited to assessment of prostate pathology include the ability to examine images at different magnifications as well as to view histology and immunohistochemistry side-by-side on the screen. Use of WSI/VM would also solve the difficulty in obtaining multiple identical copies of small lesions in prostate biopsies for teaching and proficiency testing. It would also permit annotation of the virtual slides, and has been used in a study of inter-observer variation of Gleason grading to facilitate precise identification of the foci on which grading decisions had been based. However, the large number of sections examined from each set of prostate biopsies would greatly increase time required for scanning as well as the size of the digital file, and would also be an issue if digital archiving of prostate biopsies is contemplated. Z-scanning of glass slides, a process that increases scanning time and file size would be required to permit focusing a virtual slide up and down to assess subtle nuclear features such as nucleolar prominence. The common use of large blocks to process prostatectomy specimens would also be an issue, as few currently available scanners can scan such blocks. A major component of proficiency testing of prostate biopsy assessment involves screening of the cores to detect small atypical foci. However, screening virtual slides of wavy fragmented prostate cores using a computer mouse aided by an overview image is very different from screening glass slides using a microscope stage. Hence, it may be more appropriate in this setting to mark the lesional area and focus only on the interpretation component of competency testing. Other issues limiting the use of digital pathology in prostate pathology include the cost of high quality slide scanners for WSI and high resolution monitors for VM as well as the requirement for fast Internet connection as even a subtle delay in presentation of images on the screen may be very disturbing for a pathologist used to the rapid viewing of glass slides under a microscope. However, these problems are likely to be overcome by technological advances in the future.

Published
2012

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