Skip to main content
Log in

Organoide zur Weiterentwicklung der intraoperativen Diagnostik

Organoids for the advancement of intraoperative diagnostic procedures

  • Leitthema
  • Published:
Der Urologe Aims and scope Submit manuscript

Zusammenfassung

Im Rahmen von onkologischen Operationen besteht immer die Abwägung zwischen onkologischer Sicherheit und dem Funktionserhalt. Dies gilt insbesondere bei Operationen im Becken, aufgrund der engen Lagebeziehung zur Muskulatur des Beckenbodens sowie Gefäß und Nervenverläufen. Aktuell dienen zumeist Risikomodelle, präoperative Bildgebung, die Einschätzung des Operateurs sowie der intraoperative Schnellschnitt als Entscheidungsgrundlage. Neue Bildgebungstechniken sowie Standardisierung im Schnellschnitt haben diese in den letzten Jahren deutlich verbessert. Es verbleiben jedoch weiterhin Einschränkungen durch zeitliche Verzögerung sowie erschwerte korrekte anatomische Zuordnung der zu untersuchenden Präparate. Alternative intraoperative Verfahren könnten diese Grenzen in der Zukunft überwinden. Patientenabgeleitete Organoide haben sich in den letzten Jahren zu einem wichtigen neuen Forschungsvehikel entwickelt. Sie basieren auf Tumorstammzellen, die unter speziellen Kulturbedingungen dreidimensionale Replikate des Ursprungsgewebes formen. Damit sind sie optimal geeignet zur Testung von individuellen Systemtherapien aber auch als Validierungstechnik für neue diagnostische Verfahren. Das durch die Deutsche Forschungsgemeinschaft geförderte Graduiertenkolleg 2543/I analysiert in einem interdisziplinären Team das Potenzial neuer diagnostischer Methoden im Hinblick auf die intraoperative real-time Diagnostik in Ergänzung zu konventionellen Schnellschnittdiagnostik

Abstract

In the context of cancer surgery, there is always a trade-off between oncological safety and preservation of function. This is especially true in pelvic surgery due to the close relationship to the pelvic floor muscles, blood supply and nerves. Currently, risk models, preoperative imaging, the surgeon’s assessment, and the intraoperative frozen section serve as the basis for decision-making. New imaging techniques and standardization in frozen section have significantly improved this in recent years. However, limitations remain due to time delays as well as more difficult correct anatomical assignment in the follow-up. Alternative intraoperative techniques may overcome this limitation in the future. Patient-derived organoids have emerged as an important new research vehicle in recent years. They are based on tumor stem cells that, under special culture conditions, form three-dimensional replicas of the original tissue. This makes them ideally suited for testing individual system therapies but also as a validation technique for new intraoperative diagnostic procedures. The Research Training Group 2543/I, which is funded by the German Research Foundation, is researching the potential of new diagnostic methods in an interdisciplinary team regarding validation in addition to intraoperative frozen sections.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Abb. 1
Abb. 2
Abb. 3
Abb. 4

Literatur

  1. Amend B, Hennenlotter J, Kuehs U, Laible I, Anastasiadis A, Schilling D et al (2013) Prostatic peripheral nerve distribution may impact the functional outcome of nerve-sparing prostatectomy. World J Urol 31(2):377–382

    Article  CAS  Google Scholar 

  2. Vale CL, Fisher D, Kneebone A, Parker C, Pearse M, Richaud P et al (2020) Adjuvant or early salvage radiotherapy for the treatment of localised and locally advanced prostate cancer: a prospectively planned systematic review and meta-analysis of aggregate data. Lancet. https://doi.org/10.1016/s0140-6736(20)31952-8

    Article  PubMed  PubMed Central  Google Scholar 

  3. Martini A, Gandaglia G, Fossati N, Scuderi S, Bravi CA, Mazzone E et al (2021) Defining clinically meaningful positive surgical margins in patients undergoing radical prostatectomy for localised prostate cancer. Eur Urol Oncol 4(1):42–48. https://doi.org/10.1016/j.euo.2019.03.006

    Article  PubMed  Google Scholar 

  4. Zaffuto E, Gandaglia G, Fossati N, Dell’Oglio P, Moschini M, Cucchiara V et al (2017) Early postoperative radiotherapy is associated with worse functional outcomes in patients with prostate cancer. J Urol 197(3):669–675

    Article  Google Scholar 

  5. Del Giudice F, Leonardo C, Simone G, Pecoraro M, De Berardinis E, Cipollari S et al (2020) Preoperative detection of vesical imaging-reporting and data system (VI-RADS) score 5 reliably identifies extravesical extension of urothelial carcinoma of the urinary bladder and predicts significant delayed time to cystectomy: time to reconsider the need for primary deep transurethral resection of bladder tumour in cases of locally advanced disease? BJU Int 126(5):610–619

    Article  CAS  Google Scholar 

  6. Zhang F, Liu C‑L, Chen Q, Shao S‑C, Chen S‑Q (2019) Accuracy of multiparametric magnetic resonance imaging for detecting extracapsular extension in prostate cancer: a systematic review and meta-analysis. Br J Radiol 92(1104):20190480

    Article  Google Scholar 

  7. Sighinolfi MC, Eissa A, Spandri V, Puliatti S, Micali S, Reggiani Bonetti L et al (2020) Positive surgical margin during radical prostatectomy: overview of sampling methods for frozen sections and techniques for the secondary resection of the neurovascular bundles. BJU Int. https://doi.org/10.1111/bju.15024

    Article  PubMed  PubMed Central  Google Scholar 

  8. Lavery HJ, Xiao G-Q, Nabizada‐Pace F, Mikulasovich M, Unger P, Samadi DB (2011) ‘Mohs surgery of the prostate’: the utility of in situ frozen section analysis during robotic prostatectomy. BJU international 107(6):975–979

    Article  Google Scholar 

  9. Nunez AL, Giannico GA, Mukhtar F, Dailey V, El-Galley R, Hameed O (2016) Frozen section evaluation of margins in radical prostatectomy specimens: a contemporary study and literature review. Ann Diagn Pathol 24:11–18

    Article  Google Scholar 

  10. Dinneen E, Haider A, Grierson J, Freeman A, Oxley J, Briggs T et al (2021) NeuroSAFE frozen section during robot-assisted radical prostatectomy (RARP): peri-operative and histopathological outcomes from the NeuroSAFE PROOF feasibility randomised controlled trial. BJU Int 127(6):676–686. https://doi.org/10.1111/bju.15256

    Article  PubMed  Google Scholar 

  11. Cahill LC, Wu Y, Yoshitake T, Ponchiardi C, Giacomelli MG, Wagner AA et al (2020) Nonlinear microscopy for detection of prostate cancer: analysis of sensitivity and specificity in radical prostatectomies. Mod Pathol 33(5):916–923

    Article  CAS  Google Scholar 

  12. Panebianco V, Barchetti F, Sciarra A, Ciardi A, Indino EL, Papalia R et al (2015) Multiparametric magnetic resonance imaging vs. standard care in men being evaluated for prostate cancer: a randomized study. Urol Oncol 33(1):17.e1–e7

    Article  Google Scholar 

  13. Ström P, Kartasalo K, Olsson H, Solorzano L, Delahunt B, Berney DM et al (2020) Artificial intelligence for diagnosis and grading of prostate cancer in biopsies: a population-based, diagnostic study. Lancet Oncol 21(2):222–232

    Article  Google Scholar 

  14. olde Heuvel J, van der Poel HG, Bekers EM, Grootendorst MR, Vyas KN, Slump CH et al (2020) 68 Ga-PSMA Cerenkov luminescence imaging in primary prostate cancer: first-in-man series. Eur J Nucl Med Mol Imaging 47(11):2624–2632

    Article  Google Scholar 

  15. Allen WM, Foo KY, Zilkens R, Kennedy KM, Fang Q, Chin L et al (2018) Clinical feasibility of optical coherence micro-elastography for imaging tumor margins in breast-conserving surgery. Biomed Opt Express 9(12):6331–6349

    Article  Google Scholar 

  16. Fuks D, Pierangelo A, Validire P, Lefevre M, Benali A, Trebuchet G et al (2019) Intraoperative confocal laser endomicroscopy for real-time in vivo tissue characterization during surgical procedures. Surg Endosc 33(5):1544–1552

    Article  Google Scholar 

  17. Calin VL, Mihailescu M, Costea RV, Dumitru A, Patrascu O‑M, Brehar F et al (Hrsg) (2019) Optical biomarkers for detection of malignant tissue using digital holographic microscopy. European Conference on Biomedical Optics, München

    Google Scholar 

  18. Toulouse A, Drozella J, Thiele S, Giessen H, Herkommer A (2021) 3D-printed miniature spectrometer for the visible range with a 100× 100 μm 2 footprint. Light: Advanced Manufacturing 2(1):1–11

    Google Scholar 

  19. Daum R, Brauchle EM, Berrio DAC, Jurkowski TP, Schenke-Layland K (2019) Non-invasive detection of DNA methylation states in carcinoma and pluripotent stem cells using Raman microspectroscopy and imaging. Sci Rep 9(1):1–13

    Article  CAS  Google Scholar 

  20. Kumar S, Srinivasan A, Nikolajeff F (2018) Role of infrared spectroscopy and imaging in cancer diagnosis. Curr Med Chem 25(9):1055–1072

    Article  CAS  Google Scholar 

  21. Pinto M, Zorn KC, Tremblay J‑P, Desroches J, Dallaire F, Aubertin K et al (2019) Integration of a Raman spectroscopy system to a robotic-assisted surgical system for real-time tissue characterization during radical prostatectomy procedures. J Biomed Opt 24(2):25001

    Article  CAS  Google Scholar 

  22. Pathiraja AA, Weerakkody RA, von Roon AC, Ziprin P, Bayford R (2020) The clinical application of electrical impedance technology in the detection of malignant neoplasms: a systematic review. J Transl Med 18:1–11

    Article  Google Scholar 

  23. Morgan K, Gamal W, Samuel K, Morley SD, Hayes PC, Bagnaninchi P et al (2020) Application of impedance-based techniques in hepatology research. J Clin Med 9(1):50

    Article  CAS  Google Scholar 

  24. Liebsch M, Grune B, Seiler A, Butzke D, Oelgeschläger M, Pirow R et al (2011) Alternatives to animal testing: current status and future perspectives. Springer,

    Google Scholar 

  25. Clevers H (2016) Modeling development and disease with organoids. Cell 165(7):1586–1597

    Article  CAS  Google Scholar 

  26. Vlachogiannis G, Hedayat S, Vatsiou A, Jamin Y, Fernández-Mateos J, Khan K et al (2018) Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. Science 359(6378):920–926

    Article  CAS  Google Scholar 

  27. de Poel E, Lefferts J, Beekman J (2020) Intestinal organoids for cystic fibrosis research. J Cyst Fibros 19:60–S4

    Article  Google Scholar 

  28. Suarez-Ibarrola R, Sigle A, Eklund M, Eberli D, Miernik A, Benndorf M et al (2021) Artificial intelligence in magnetic resonance imaging-based prostate cancer diagnosis: where do we stand in 2021? Eur Urol Focus. https://doi.org/10.1016/j.euf.2021.03.020

    Article  PubMed  Google Scholar 

  29. Kim E, Choi S, Kang B, Kong J, Kim Y, Yoon WH et al (2020) Creation of bladder assembloids mimicking tissue regeneration and cancer. Nature 588(7839):664–669. https://doi.org/10.1038/s41586-020-3034-x

    Article  CAS  PubMed  Google Scholar 

  30. Yoshida T, Okuyama H, Nakayama M, Endo H, Nonomura N, Nishimura K et al (2015) High-dose chemotherapeutics of intravesical chemotherapy rapidly induce mitochondrial dysfunction in bladder cancer-derived spheroids. Cancer Sci 106(1):69–77

    Article  CAS  Google Scholar 

  31. Drost J, Clevers H (2017) Translational applications of adult stem cell-derived organoids. Development 144(6):968–975

    Article  CAS  Google Scholar 

  32. Mullenders J, de Jongh E, Brousali A, Roosen M, Blom JP, Begthel H et al (2019) Mouse and human urothelial cancer organoids: a tool for bladder cancer research. Proc Natl Acad Sci USA 116(10):4567–4574

    Article  CAS  Google Scholar 

Download references

Förderung

Die Arbeiten, die in diesem Artikel beschrieben werden, entstanden teilweise im Rahmen der Tätigkeiten im Graduiertenkolleg 2543/1 „Intraoperative Multisensorische Gewebedifferenzierung in der Onkologie“ (Projekt ID 40947457), gefördert von der Deutschen Forschungsgemeinschaft (DFG).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to N. Harland.

Ethics declarations

Interessenkonflikt

N. Harland, B. Amend, N. Lipke, S. Y. Brucker, F. Fend, A. Herkommer, H. Lensch, O. Sawodny, T.E. Schäffer, K. Schenke-Layland, C. Tarín Sauer, W. Aicher und A. Stenzl geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

Additional information

figure qr

QR-Code scannen & Beitrag online lesen

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Harland, N., Amend, B., Lipke, N. et al. Organoide zur Weiterentwicklung der intraoperativen Diagnostik. Urologe 60, 1159–1166 (2021). https://doi.org/10.1007/s00120-021-01595-5

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00120-021-01595-5

Schlüsselwörter

Keywords

Navigation