Chemosaturation Percutaneous Hepatic Perfusion (CS-PHP) with Melphalan: Evaluation of 2D-Perfusion Angiography (2D-PA) for Leakage Detection of the Venous Double-Balloon Catheter

  • Cornelia L. A. Dewald
  • Timo C. Meine
  • Hinrich M. B. Winther
  • Roman Kloeckner
  • Sabine K. Maschke
  • Martha M. Kirstein
  • Arndt Vogel
  • Frank K. Wacker
  • Bernhard C. Meyer
  • Julius Renne
  • Jan B. HinrichsEmail author
Clinical Investigation Imaging
Part of the following topical collections:
  1. Imaging



To evaluate the feasibility of 2D-perfusion angiography (2D-PA) for detecting leakage of the double-balloon catheter used for chemosaturation percutaneous hepatic perfusion (CS-PHP).

Materials and Methods

Overall, 112 CS-PHP (09/2015-09/2018) in 52 patients were retrospectively screened for leakage alongside the double-balloon catheter on standard venograms. Finally, 18 procedures with visually detected leakage were included. Fifteen consecutive procedures without leakage served as control. To evaluate 2D-PA for leakage detection, the acquired digital subtraction venograms were post-processed. For each balloon, two different target ROIs were evaluated to assess a possible impact of localization and shape of the ROIs. Time to peak (TTP), peak density (PD), area under the curve (AUC), and ratios of target ROI/reference ROIs (PDtROI/PDREF; AUCtROI/AUCREF; and TTPtROI/TTPREF) were calculated.


Leakages were located as follows: 15/18 cranial and 3/18 caudal. At the cranial balloon both ROIs showed a significant decrease in PDtROI/PDREF and AUCtROI/AUCREF (ROI1: p < 0.0001; p < 0.0001; ROI2: p < 0.0001; p < 0.0001) and a significant increase in TTPtROI/TTPREF (ROI1: p = 0.0009; ROI2: p = 0.0003) after double-balloon correction. Following balloon adjustment, the 2D-PA ratios (PD and AUC) of the tested ROIs differed significantly (p < 0.05). The inter-individual comparison of the 2D-PA parameters of the group with leakage before balloon correction and the non-leakage group showed significantly different 2D-PA values for the cranial balloon in both ROIs (p < 0.05). No significant differences were found for the caudal balloon.


2D-PA provides a feasible tool for detecting leakages alongside the cranial portion of the double-balloon catheter used in CS-PHP. The shape and position of the ROIs used to assess perfusion and flow have an impact on the measurements.


2D-perfusion angiography Chemosaturation Percutaneous hepatic perfusion Double-balloon catheter Leakage 



2D-perfusion angiography


Activated clotting time


Area under the curve


Ratio of the target ROI to the reference ROI for AUC


Chemosaturation percutaneous hepatic perfusion


Digital subtraction angiography


Inferior vena cava


Peak density


Ratio of the target ROI to the reference ROI for PD


Region of interest


Reference region of interest


Transarterial chemoembolization


Transjugular intrahepatic portosystemic shunt


Target region of interest


Time to peak


Ratio of the target ROI to the reference ROI for TTP


Author’s Contribution

All authors significantly contributed to the design and composition, data analysis, and data interpretation for this study. Furthermore, all of the authors drafted the article or substantially revised it due to the important intellectual content. All of the authors gave their final consent for this version of the manuscript to be published.

Compliance with Ethical Standards

Conflict of interest

The authors of this manuscript declare relationships with the following companies: Siemens Healthcare and ProMedicus (Bernhard Meyer and Frank Wacker, outside the submitted work). The remaining authors declare no relationships with any companies whose products or services may be related to the subject matter of the article.

Ethical Approval

Our local ethics committee approved our protocol, and written informed consent was obtained from each study patient. The study follows the ethical standards of the Declaration of Helsinki. The article includes no identifying information.

Human and Animal Rights

This study follows the ethical standards of the Declaration of Helsinki. Animal studies are not part of this article (does not apply to this article).


  1. 1.
    Hughes MS, Zager J, Faries M, Alexander HR, Royal RE, Wood B, et al. Results of a randomized controlled multicenter phase III trial of percutaneous hepatic perfusion compared with best available care for patients with melanoma liver metastases. Ann Surg Oncol. 2016;23:1309–19.CrossRefGoogle Scholar
  2. 2.
    Marquardt S, Kirstein MM, Brüning R, Zeile M, Ferrucci PF, Prevoo W, et al. Percutaneous hepatic perfusion (chemosaturation) with melphalan in patients with intrahepatic cholangiocarcinoma: European multicentre study on safety, short-term effects and survival. Eur Radiol. 2018;383:2168.Google Scholar
  3. 3.
    Kirstein MM, Marquardt S, Jedicke N, Marhenke S, Koppert W, Manns MP, et al. Safety and efficacy of chemosaturation in patients with primary and secondary liver tumors. J Cancer Res Clin Oncol. 2017;143:2113–21.CrossRefGoogle Scholar
  4. 4.
    Forster MR, Rashid OM, Perez MC, Choi J, Chaudhry T, Zager JS. Chemosaturation with percutaneous hepatic perfusion for unresectable metastatic melanoma or sarcoma to the liver: a single institution experience. J Surg Oncol. 2014;109:434–9.CrossRefGoogle Scholar
  5. 5.
    Vogel A, Gupta S, Zeile M, von Haken R, Brüning R, Lotz G, et al. Chemosaturation percutaneous hepatic perfusion: a systematic review. Adv Ther. 2017;33:2122–38.CrossRefGoogle Scholar
  6. 6.
    de Leede EM, Burgmans MC, Meijer TS, Martini CH, Tijl FGJ, Vuyk J, et al. Prospective clinical and pharmacological evaluation of the Delcath System’s second-generation (GEN2) hemofiltration system in patients undergoing percutaneous hepatic perfusion with melphalan. Cardiovasc Interv Radiol. 2017;40:1196–205.CrossRefGoogle Scholar
  7. 7.
    McEwan PE, Bailey L, Trost D, Scull C, Keating JH, Williams M, et al. Percutaneous hepatic perfusion with filtered melphalan for localized treatment of metastatic hepatic disease: a risk assessment. Int J Toxicol. 2018;37:1091581818811306–447.CrossRefGoogle Scholar
  8. 8.
    Maschke SK, Renne J, Werncke T, Olsson KM, Hoeper MM, Wacker FK, et al. Chronic thromboembolic pulmonary hypertension: evaluation of 2D-perfusion angiography in patients who undergo balloon pulmonary angioplasty. Eur Radiol. 2017;27:4264–70.CrossRefGoogle Scholar
  9. 9.
    Maschke SK, Werncke T, Klöckner R, Rodt T, Renne J, Kirstein MM, et al. Quantification of perfusion reduction by using 2D-perfusion angiography following transarterial chemoembolization with drug-eluting beads. Abdom Radiol (NY). 2017;65:87–9.Google Scholar
  10. 10.
    Maschke SK, Werncke T, Renne J, Kloeckner R, Marquardt S, Kirstein MM, et al. Transjugular intrahepatic portosystemic shunt (TIPS) dysfunction: quantitative assessment of flow and perfusion changes using 2D-perfusion angiography following shunt revision. Abdom Radiol (NY). 2018;43:2868–75.CrossRefGoogle Scholar
  11. 11.
    Murray T, Rodt T, Lee MJ. Two-dimensional perfusion angiography of the foot: technical considerations and initial analysis. J Endovasc Ther. 2016;23:58–64.CrossRefGoogle Scholar
  12. 12.
    Reekers JA, Koelemay MJW, Marquering HA, van Bavel ET. Functional imaging of the foot with perfusion angiography in critical limb ischemia. Cardiovasc Interv Radiol. 2016;39:183–9.CrossRefGoogle Scholar
  13. 13.
    Zhou M, Su Z, Shi Z, Fu W, Meng X, Wang Y, et al. Application of color-coded quantitative digital subtraction angiography in predicting the outcomes of immediate type I and type III endoleaks. J Vasc Surg. 2017;66:760–7.CrossRefGoogle Scholar
  14. 14.
    Tan RY, Chong TT, Tsai FC, Pang SC, Lee KG, Gogna A, et al. A pilot study on adjunctive use of parametric colour-coded digital subtraction angiography in endovascular interventions of haemodialysis access. BMC Med Imaging. 2018;18:28.CrossRefGoogle Scholar
  15. 15.
    Burgmans MC, de Leede EM, Martini CH, Kapiteijn E, Vahrmeijer AL, van Erkel AR. percutaneous isolated hepatic perfusion for the treatment of unresectable liver malignancies. Cardiovasc Interv Radiol. 2016;39:801–14.CrossRefGoogle Scholar
  16. 16.
    Hinrichs JB, Murray T, Akin M, Lee M, Brehm MU, Wilhelmi M, et al. Evaluation of a novel 2D perfusion angiography technique independent of pump injections for assessment of interventional treatment of peripheral vascular disease. Int J Cardiovasc Imaging. 2017;33:295–301.CrossRefGoogle Scholar
  17. 17.
    Karydis I, Gangi A, Wheater MJ, Choi J, Wilson I, Thomas K, et al. Percutaneous hepatic perfusion with melphalan in uveal melanoma: a safe and effective treatment modality in an orphan disease. J Surg Oncol. 2018;117:1170–8.CrossRefGoogle Scholar
  18. 18.
    Jens S, Marquering HA, Koelemay MJW, Reekers JA. Perfusion angiography of the foot in patients with critical limb ischemia: description of the technique. Cardiovasc Interv Radiol. 2015;38:201–5.CrossRefGoogle Scholar
  19. 19.
    Kim AH, Shevitz AJ, Morrow KL, Kendrick DE, Harth K, Baele H, et al. Characterizing tissue perfusion after lower extremity intervention using two-dimensional color-coded digital subtraction angiography. J Vasc Surg. 2017;66:1464–72.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2019

Authors and Affiliations

  • Cornelia L. A. Dewald
    • 1
  • Timo C. Meine
    • 1
  • Hinrich M. B. Winther
    • 1
  • Roman Kloeckner
    • 2
  • Sabine K. Maschke
    • 1
  • Martha M. Kirstein
    • 3
  • Arndt Vogel
    • 3
  • Frank K. Wacker
    • 1
  • Bernhard C. Meyer
    • 1
  • Julius Renne
    • 1
  • Jan B. Hinrichs
    • 1
    Email author
  1. 1.Department of Diagnostic and Interventional Radiology, Member of the German Center for Lung Research (DZL), Institute for Diagnostic and Interventional RadiologyHannover Medical SchoolHannoverGermany
  2. 2.Department of Diagnostic and Interventional RadiologyJohannes Gutenberg-University Medical CentreMainzGermany
  3. 3.Department of Gastroenterology, Hepatology and EndocrinologyHannover Medical SchoolHannoverGermany

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