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Non-invasive MR assessment of macroscopic and microscopic vascular abnormalities in the rectal tumour-surrounding mesorectum

  • Oncology
  • Published:
European Radiology Aims and scope Submit manuscript

Abstract

Objectives

To evaluate the MRI macroscopic and microscopic parameters of mesorectal vasculature in rectal cancer patients.

Methods

Thirteen patients with rectal adenocarcinoma underwent a dynamic contrast-enhanced MRI at 1.5 T using a blood pool agent at the primary staging. Mesorectal macrovascular features, i.e., the number of vascular branches, average diameter and length, were assessed from baseline-subtracted post-contrast images by two independent readers. Mesorectal microvascular function was investigated by means of area under the enhancement-time curve (AUC). Histopathology served as reference standard of the tumour response to CRT.

Results

The average vessel branching in the mesorectum around the tumour and normal rectal wall was 8.2 ± 3.8 and 1.7 ± 1.3, respectively (reader1: p = 0.001, reader2: p = 0.002). Similarly, the tumour-surrounding mesorectum displayed circa tenfold elevated AUC (p = 0.01). Interestingly, patients with primary node involvement had a twofold higher number of macrovascular branches compared to those with healthy nodes (reader1: p = 0.005 and reader2: p = 0.03). A similar difference was observed between good and poor responders to CRT, whose tumour-surrounding mesorectum displayed 10.7 ± 3.4 and 5.6 ± 1.5 vessels, respectively (reader1/reader2: p = 0.02).

Conclusions

We showed at baseline MRI of rectal tumours a significantly enhanced macrovascular structure and microvascular function in rectal tumour-surrounding mesorectum, and the association of primary mesorectal macrovascular parameters with node involvement and therapy response.

Key Points

• Vascular MRI reveals macrovascular and microvascular abnormalities in the rectal tumour-surrounding mesorectum.

• Formation of highly vascular stroma precedes the actual tumour invasion.

• High macrovascular parameters are associated with node involvement.

• Mesorectal vascular network differs for good and poor responders.

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Abbreviations

a.u.:

Arbitrary units

AUC:

Area under the contrast enhancement-time curve

cN:

Clinical (MRI-based) nodal stage

CRT:

Neoadjuvant chemoradiotherapy

DCE-MRI:

Dynamic contrast-enhanced magnetic resonance imaging

EMVI:

Extramural venous invasion

H&E:

Haematoxylin and eosin staining

ROI:

Region of interest

SI:

Signal intensity

T1:

Longitudinal relaxation time

T2:

Transversal relaxation time

TME:

Total mesorectal excision

TRG:

Tumour regression grade

(y)pTN:

Pathological tumour and node stage

References

  1. Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285:1182–1186

    Article  CAS  PubMed  Google Scholar 

  2. Ferrara N, Kerbel RS (2005) Angiogenesis as a therapeutic target. Nature 438:967–974

    Article  CAS  PubMed  Google Scholar 

  3. Weidner N, Semple JP, Welch WR, Folkman J (1991) Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma. N Engl J Med 324:1–8

    Article  CAS  PubMed  Google Scholar 

  4. Weidner N, Carroll PR, Flax J, Blumenfeld W, Folkman J (1993) Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma. Am J Pathol 143:401–409

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Li CY, Shan S, Huang Q, Braun RD, Lanzen J, Hu K et al (2000) Initial stages of tumor cell-induced angiogenesis: evaluation via skin window chambers in rodent models. J Natl Cancer Inst 92:143–147

    Article  CAS  PubMed  Google Scholar 

  6. Nowacki P, Kojder I (2001) Peritumoral angiogenesis around primary and metastatic brain neoplasms. Morphometric analysis. Folia Neuropathol 39:95–102

    CAS  PubMed  Google Scholar 

  7. Yu DC, Chen J, Ding YT (2010) Hypoxic and highly angiogenic non-tumor tissues surrounding hepatocellular carcinoma: the 'niche' of endothelial progenitor cells. Int J Mol Sci 11:2901–2909

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Isaka N, Padera TP, Hagendoorn J, Fukumura D, Jain RK (2004) Peritumor lymphatics induced by vascular endothelial growth factor-C exhibit abnormal function. Cancer Res 64:4400–4404

    Article  CAS  PubMed  Google Scholar 

  9. Winkler F, Kienast Y, Fuhrmann M, Von Baumgarten L, Burgold S, Mitteregger G et al (2009) Imaging glioma cell invasion in vivo reveals mechanisms of dissemination and peritumoral angiogenesis. Glia 57:1306–1315

    Article  PubMed  Google Scholar 

  10. Sica G, Lama G, Anile C, Geloso MC, La Torre G, De Bonis P et al (2011) Assessment of angiogenesis by CD105 and nestin expression in peritumor tissue of glioblastoma. Int J Oncol 38:41–49

    PubMed  Google Scholar 

  11. Sardanelli F, Iozzelli A, Fausto A, Carriero A, Kirchin MA (2005) Gadobenate dimeglumine-enhanced MR imaging breast vascular maps: association between invasive cancer and ipsilateral increased vascularity. Radiology 235:791–797

    Article  PubMed  Google Scholar 

  12. Bullitt E, Zeng D, Gerig G, Aylward S, Joshi S, Smith JK et al (2005) Vessel tortuosity and brain tumor malignancy: a blinded study. Acad Radiol 12:1232–1240

    Article  PubMed  PubMed Central  Google Scholar 

  13. Smith NJ, Barbachano Y, Norman AR, Swift RI, Abulafi AM, Brown G (2008) Prognostic significance of magnetic resonance imaging-detected extramural vascular invasion in rectal cancer. Br J Surg 95:229–236

    Article  CAS  PubMed  Google Scholar 

  14. Smith NJ, Shihab O, Arnaout A, Swift RI, Brown G (2008) MRI for detection of extramural vascular invasion in rectal cancer. AJR Am J Roentgenol 191:1517–1522

    Article  PubMed  Google Scholar 

  15. Betge J, Pollheimer MJ, Lindtner RA, Kornprat P, Schlemmer A, Rehak P et al (2012) Intramural and extramural vascular invasion in colorectal cancer: prognostic significance and quality of pathology reporting. Cancer 118:628–638

    Article  PubMed  Google Scholar 

  16. Kim YC, Kim JK, Kim MJ, Lee JH, Kim YB, Shin SJ (2015) Feasibility of mesorectal vascular invasion in predicting early distant metastasis in patients with stage T3 rectal cancer based on rectal MRI. Eur Radiol 1–9. doi:10.1007/s00330-015-3837-6

  17. Rohrer M (2008) MRI Contrast Media — Introduction and Basic Properties of the Blood Pool Agent Gadofosveset (Vasovist®) in Clinical Blood Pool MR Imaging, Leiner T, Goyen M, Rohrer M, Schönberg SO (Eds.). Springer Medizin Verlag, Heidelberg

  18. Turetschek K, Floyd E, Helbich T, Roberts TP, Shames DM, Wendland MF et al (2001) MRI assessment of microvascular characteristics in experimental breast tumors using a new blood pool contrast agent (MS-325) with correlations to histopathology. J Magn Reson Imaging 14:237–242

    Article  CAS  PubMed  Google Scholar 

  19. Maas M, Nelemans PJ, Valentini V, Das P, Rodel C, Kuo LJ et al (2010) Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol 11:835–844

    Article  PubMed  Google Scholar 

  20. Maas M, Beets-Tan RG, Lambregts DM, Lammering G, Nelemans PJ, Engelen SM et al (2011) Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. J Clin Oncol 29:4633–4640

    Article  PubMed  Google Scholar 

  21. Lambregts DM, Beets GL, Maas M, Kessels AG, Bakers FC, Cappendijk VC et al (2011) Accuracy of gadofosveset-enhanced MRI for nodal staging and restaging in rectal cancer. Ann Surg 253:539–545

    Article  PubMed  Google Scholar 

  22. Martens MH, Subhani S, Heijnen LA, Lambregts DM, Buijsen J, Maas M et al (2015) Can perfusion MRI predict response to preoperative treatment in rectal cancer? Radiother Oncol 114:218–223

    Article  PubMed  Google Scholar 

  23. Quirke P, Durdey P, Dixon MF, Williams NS (1986) Local recurrence of rectal adenocarcinoma due to inadequate surgical resection. Histopathological study of lateral tumour spread and surgical excision. Lancet 2:996–999

    Article  CAS  PubMed  Google Scholar 

  24. Mandard AM, Dalibard F, Mandard JC, Marnay J, Henry-Amar M, Petiot JF et al (1994) Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer 73:2680–2686

    Article  CAS  PubMed  Google Scholar 

  25. Vecchio FM, Valentini V, Minsky BD, Padula GD, Venkatraman ES, Balducci M et al (2005) The relationship of pathologic tumor regression grade (TRG) and outcomes after preoperative therapy in rectal cancer. Int J Radiat Oncol Biol Phys 62:752–760

    Article  PubMed  Google Scholar 

  26. Shapiro SS, Wilk MB (1965) An analysis of variance test for normality (complete samples). Biometrika 52:591–611

    Article  Google Scholar 

  27. Moore KL, Dalley AF, Agur AM (2013) Clinically oriented anatomy, 7th Edition, Lippincott Williams & Wilkins, Baltimore

  28. Bullitt E, Lin NU, Smith JK, Zeng D, Winer EP, Carey LA et al (2007) Blood vessel morphologic changes depicted with MR angiography during treatment of brain metastases: a feasibility study. Radiology 245:824–830

    Article  PubMed  PubMed Central  Google Scholar 

  29. Parikh AH, Smith JK, Ewend MG, Bullitt E (2004) Correlation of MR perfusion imaging and vessel tortuosity parameters in assessment of intracranial neoplasms. Technol Cancer Res Treat 3:585–590

    Article  PubMed  PubMed Central  Google Scholar 

  30. Bullitt E, Ewend MG, Aylward S, Lin W, Gerig G, Joshi S et al (2004) Abnormal vessel tortuosity as a marker of treatment response of malignant gliomas: preliminary report. Technol Cancer Res Treat 3:577–584

    Article  PubMed  PubMed Central  Google Scholar 

  31. Zhang L, Yang N, Park JW, Katsaros D, Fracchioli S, Cao G et al (2003) Tumor-derived vascular endothelial growth factor up-regulates angiopoietin-2 in host endothelium and destabilizes host vasculature, supporting angiogenesis in ovarian cancer. Cancer Res 63:3403–3412

    CAS  PubMed  Google Scholar 

  32. Galvin JM, De Neve W (2007) Intensity modulating and other radiation therapy devices for dose painting. J Clin Oncol 25:924–930

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The scientific guarantor of this publication is Regina G.H. Beets-Tan, PhD, MD. The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. The authors state that this work has not received any funding.

No complex statistical methods were necessary for this paper. Institutional Review Board approval was obtained. Written informed consent was obtained from all subjects (patients) in this study.

Methodology: prospective, experimental, performed at one institution.

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Author notes

    Authors and Affiliations

    1. Department of Radiology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, 6202 AZ, Maastricht, Netherlands

      Ewelina Kluza, Jean-Paul J. E. Kleijnen, Milou H. Martens, Monique Maas, Cécile R. L. P. N. Jeukens & Regina G. H. Beets-Tan

    2. Department of Pathology, Maastricht University Medical Center, Maastricht, Netherlands

      Dorit Rennspiess, Robert G. Riedl & Axel zur Hausen

    3. Department of Surgery, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, Netherlands

      Milou H. Martens & Geerard L. Beets

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    1. Ewelina Kluza
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    Correspondence to Regina G. H. Beets-Tan.

    Additional information

    Jean-Paul J. E. Kleijnen and Milou H. Martens contributed equally to this work.

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    Kluza, E., Kleijnen, JP.J.E., Martens, M.H. et al. Non-invasive MR assessment of macroscopic and microscopic vascular abnormalities in the rectal tumour-surrounding mesorectum. Eur Radiol 26, 1311–1319 (2016). https://doi.org/10.1007/s00330-015-3955-1

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