Biliary duct stenosis after image-guided high-dose-rate interstitial brachytherapy of central and hilar liver tumors

A systematic analysis of 102 cases
  • Maciej PowerskiEmail author
  • Susanne Penzlin
  • Peter Hass
  • Ricarda Seidensticker
  • Konrad Mohnike
  • Robert Damm
  • Ingo Steffen
  • Maciej Pech
  • Günther Gademann
  • Jens Ricke
  • Max Seidensticker
Original Article



Image-guided high-dose-rate interstitial brachytherapy (iBT) with iridium-192 is an effective treatment option for patients with liver malignancies. Little is known about long-term radiation effects on the bile duct system when central hepatic structures are exposed to iBT. This retrospective analysis investigates the occurrence of posthepatic cholestasis (PHC) and associated complications in patients undergoing iBT.

Materials and methods

We identified patients who underwent iBT of hepatic malignancies and had point doses of ≥1 Gy to central bile duct structures. Patients with known bile duct-related diseases or prior bile duct manipulation were excluded.


102 patients were retrospectively included. Twenty-two patients (22%) developed morphologic PHC after a median of 17 (3–54) months; 18 of them were treated using percutaneous transhepatic cholangiopancreatography drainage or endoscopic retrograde cholangiopancreatography. The median point dose was 24.8 (4.4–80) Gy in patients with PHC versus 14.2 (1.8–61.7) Gy in those without PHC (p = 0.028). A dose of 20.8 Gy (biological effective dose, BED3/10 = 165/64.1 Gy) was identified to be the optimal cutoff dose (p = 0.028; 59% sensitivity, 24% specificity). Abscess/cholangitis was more common in patients with PHC compared to those without (4 of 22 vs. 2 of 80; p = 0.029). Median survival did not differ between patients with and without PHC (43 vs. 36 months; p = 0.571).


iBT of liver malignancies located near the hilum can cause PHC when the central bile ducts are exposed to high point doses. Given the long latency and absence of impact of iBT-induced PHC on median survival, the rate of cholestasis and complications seen in our patients appears to be acceptable.


Local ablation Interstitial brachytherapy Bile duct stenosis Extrahepatic cholestasis Central and hilar liver tumors 

Gallengangstenosen nach bildgeführter interstitieller Hochdosis-Brachytherapie zentraler und hilusnaher Lebertumore

Eine systematische Analyse von 102 Fällen



Die bildgestützte interstitielle Hochdosis-Brachytherapie (iBT) mit Iridium-192 ist eine effektive Methode zur Ablation hepatischer Malignome. Unklar ist die Langzeitauswirkung auf das Gallengangsystem bei Bestrahlung zentraler Leberstrukturen. Die vorgestellte retrospektive Studie eruiert den Einfluss der iBT auf die Entstehung posthepatischer Cholestasen (PHC) und vergesellschafteter Komplikationen.

Material und Methoden

Eingeschlossen wurden Patienten mit iBT hepatischer/hilusnaher Malignome mit Punktdosen ≥1 Gy an zentralen Gallengangstrukturen. Ausschlusskriterien waren gallengangassoziierte Erkrankungen oder vorherige Manipulationen an den Gallenwegen.


In die Studie konnten 102 Patienten eingeschlossen werden. Von diesen entwickelten 22 (22 %) nach im Median 17 Monaten (Spanne 3–54 Monate) eine morphologische PHC, die in 18 Fällen (18 %) mit perkutaner transhepatischer Cholangiodrainage oder endoskopischer retrograder Cholangiopankreatikographie abgeleitet werden musste. Die Punktdosis der Patienten mit PHC lag im Median bei 24,8 Gy (Spanne 4,4–80 Gy), derjenigen ohne PHC bei 14,2 Gy (Spanne 1,8–61,7 Gy; p = 0,028). Bei 20,8 Gy (biologische effektive Dosis, BED3/10 = 165/64,1 Gy) konnte ein optimaler Cut-off-Wert (Schwellendosis) ermittelt werden (p = 0,028; Sensitivität 59 %, Spezifität 24 %). Abszesse/Cholangitiden traten bei Patienten mit PHC signifikant häufiger auf als ohne (4 von 22 vs. 2 von 80; p = 0,029). Im medianen Überleben zwischen Patienten mit und ohne PHC zeigte sich kein Unterschied (43 vs. 36 Monate; p = 0,571).


Die iBT hilusnaher Lebertumore kann bei hohen Punktdosen an zentralen Gallengängen zu einer klinisch relevanten PHC führen. In Anbetracht der langen Latenzzeit und der fehlenden Auswirkung iBT-assoziierter PHC auf das mediane Überleben halten wir die ermittelte Rate an Strikturen und Komplikationen für akzeptabel.


Lokale Ablation Interstitielle Brachytherapie Gallangangsstenose Extrahepatische Cholestase Zentrale und hilusnahe Lebertumore 


Conflict of interest

M. Powerski, S. Penzlin, P. Hass, R. Seidensticker, K. Mohnike, R. Damm, I. Steffen, M. Pech, G. Gademann, J. Ricke, and M. Seidensticker declare that they have no competing interests.


  1. 1.
    Kuo I‑M, Huang S‑F, Chiang J‑M et al (2015) Clinical features and prognosis in hepatectomy for colorectal cancer with centrally located liver metastasis. World J Surg Oncol 13:92. CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Schmoll HJ, Van Cutsem E, Stein A et al (2012) ESMO consensus guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making. Ann Oncol 23:2479–2516. CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Fukasawa M, Takano S, Shindo H et al (2017) Endoscopic biliary stenting for unresectable malignant hilar obstruction. Clin J Gastroenterol 10:485–490. CrossRefPubMedGoogle Scholar
  4. 4.
    Cho Y, Kim TH, Seong J (2017) Improved oncologic outcome with chemoradiotherapy followed by surgery in unresectable intrahepatic cholangiocarcinoma. Strahlenther Onkol 193:620–629. CrossRefPubMedGoogle Scholar
  5. 5.
    Kim Y, Rhim H, Cho OK et al (2006) Intrahepatic recurrence after percutaneous radiofrequency ablation of hepatocellular carcinoma: analysis of the pattern and risk factors. Eur J Radiol 59:432–441. CrossRefPubMedGoogle Scholar
  6. 6.
    Ohnishi T, Yasuda I, Nishigaki Y et al (2008) Intraductal chilled saline perfusion to prevent bile duct injury during percutaneous radiofrequency ablation for hepatocellular carcinoma. J Gastroenterol Hepatol 23:e410–e415. CrossRefPubMedGoogle Scholar
  7. 7.
    Kahlenberg MS, Volpe C, Klippenstein DL et al (1998) Clinicopathologic effects of cryotherapy on hepatic vessels and bile ducts in a porcine model. Ann Surg Oncol 5:713–718CrossRefGoogle Scholar
  8. 8.
    Huang Y‑Z, Zhou S‑C, Zhou H, Tong M (2013) Radiofrequency ablation versus cryosurgery ablation for hepatocellular carcinoma: a meta-analysis. Hepatogastroenterology 60:1131–1135. CrossRefPubMedGoogle Scholar
  9. 9.
    Collettini F, Singh A, Schnapauff D et al (2013) Computed-tomography-guided high-dose-rate brachytherapy (CT-HDRBT) ablation of metastases adjacent to the liver hilum. Eur J Radiol 82:e509–e514. CrossRefPubMedGoogle Scholar
  10. 10.
    Ricke J, Wust P, Wieners G et al (2004) Liver malignancies: CT-guided interstitial brachytherapy in patients with unfavorable lesions for thermal ablation. J Vasc Interv Radiol 15:1279–1286. CrossRefPubMedGoogle Scholar
  11. 11.
    Grimm J, LaCouture T, Croce R et al (2011) Dose tolerance limits and dose volume histogram evaluation for stereotactic body radiotherapy. J Appl Clin Med Phys 12:3368PubMedGoogle Scholar
  12. 12.
    National Cancer Institute (2009) CTCAE v4.03. Accessed 17 July 2018Google Scholar
  13. 13.
    Osmundson EC, Wu Y, Luxton G et al (2015) Predictors of toxicity associated with stereotactic body radiation therapy to the central hepatobiliary tract. Int J Radiat Oncol Biol Phys 91:986–994. CrossRefPubMedGoogle Scholar
  14. 14.
    Toesca DAS, Osmundson EC, von Eyben R et al (2017) Central liver toxicity after SBRT: an expanded analysis and predictive nomogram. Radiother Oncol 122:130–136. CrossRefPubMedGoogle Scholar
  15. 15.
    EQD2 and BED calculator. Accessed 17 July 2018
  16. 16.
    Fowler JF (1989) The linear-quadratic formula and progress in fractionated radiotherapy. Br J Radiol 62:679–694. CrossRefPubMedGoogle Scholar
  17. 17.
    Ricke J, Wust P, Stohlmann A et al (2004) CT-guided brachytherapy. A novel percutaneous technique for interstitial ablation of liver metastases. Strahlenther Onkol 180:274–280. CrossRefPubMedGoogle Scholar
  18. 18.
    Mohnike K, Neumann K, Hass P et al (2017) Radioablation of adrenal gland malignomas with interstitial high-dose-rate brachytherapy : efficacy and outcome. Strahlenther Onkol 193:612–619. CrossRefPubMedGoogle Scholar
  19. 19.
    Ricke J, Mohnike K, Pech M et al (2010) Local response and impact on survival after local ablation of liver metastases from colorectal carcinoma by computed tomography-guided high-dose-rate brachytherapy. Int J Radiat Oncol Biol Phys 78:479–485. CrossRefPubMedGoogle Scholar
  20. 20.
    Mohnike K, Wieners G, Schwartz F et al (2010) Computed tomography-guided high-dose-rate brachytherapy in hepatocellular carcinoma: safety, efficacy, and effect on survival. Int J Radiat Oncol Biol Phys 78:172–179. CrossRefPubMedGoogle Scholar
  21. 21.
    Streitparth F, Pech M, Böhmig M et al (2006) In vivo assessment of the gastric mucosal tolerance dose after single fraction, small volume irradiation of liver malignancies by computed tomography-guided, high-dose-rate brachytherapy. Int J Radiat Oncol Biol Phys 65:1479–1486. CrossRefPubMedGoogle Scholar
  22. 22.
    Tselis N, Chatzikonstantinou G, Kolotas C et al (2013) Computed tomography-guided interstitial high dose rate brachytherapy for centrally located liver tumours: a single institution study. Eur Radiol 23:2264–2270. CrossRefPubMedGoogle Scholar
  23. 23.
    Eriguchi T, Takeda A, Sanuki N et al (2013) Acceptable toxicity after stereotactic body radiation therapy for liver tumors adjacent to the central biliary system. Int J Radiat Oncol Biol Phys 85:1006–1011. CrossRefPubMedGoogle Scholar
  24. 24.
    Ahmed M (2018) Acute cholangitis—an update. World J Gastrointest Pathophysiol 9:1–7. CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Sun Z, Zhu Y, Zhu B et al (2016) Controversy and progress for treatment of acute cholangitis after Tokyo Guidelines (TG13). Biosci Trends 10:22–26. CrossRefPubMedGoogle Scholar
  26. 26.
    Llovet JM, Brú C, Bruix J (1999) Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 19:329–338. CrossRefPubMedGoogle Scholar
  27. 27.
    Bennouna J, Sastre J, Arnold D et al (2013) Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol 14:29–37. CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Maciej Powerski
    • 1
    Email author
  • Susanne Penzlin
    • 1
  • Peter Hass
    • 2
  • Ricarda Seidensticker
    • 3
  • Konrad Mohnike
    • 4
  • Robert Damm
    • 1
  • Ingo Steffen
    • 5
  • Maciej Pech
    • 1
  • Günther Gademann
    • 2
  • Jens Ricke
    • 3
  • Max Seidensticker
    • 3
  1. 1.Klinik für Radiologie und NuklearmedizinOtto-von-Guericke UniversityMagdeburgGermany
  2. 2.Klinik für StrahlentherapieOtto-von-Guericke UniversityMagdeburgGermany
  3. 3.Klinik und Poliklinik für RadiologieKlinikum der Universität MünchenMünchenGermany
  4. 4.Diagnostisch Therapeutisches Zentrum BerlinBerlinGermany
  5. 5.Klinik für NuklearmedizinCharité Universitätsmedizin Berlin, Campus Virchow KlinikumBerlinGermany

Personalised recommendations