Skip to main content
Erschienen in: Annals of Surgical Oncology 7/2012

01.07.2012 | Hepatobiliary Tumors

Liver Injury Due to Chemotherapy-induced Sinusoidal Obstruction Syndrome Is Associated with Sinusoidal Capillarization

verfasst von: Masato Narita, MD, PhD, Elie Oussoultzoglou, MD, Marie-Pierre Chenard, MD, PhD, Pascal Fuchshuber, MD, PhD, FACS, Muddasar Rather, MD, Edoardo Rosso, MD, Pietro Addeo, MD, Daniel Jaeck, MD, PhD, FRCS, Philippe Bachellier, MD, PhD

Erschienen in: Annals of Surgical Oncology | Ausgabe 7/2012

Einloggen, um Zugang zu erhalten

Abstract

Background

Indocyanine green (ICG) retention is a validated test of hepatic function in patients with chronic liver disease. The underlying mechanism for the impairment of ICG retention in patients undergoing chemotherapy for colorectal liver metastases (CLM) remains unclear. We sought to elucidate the mechanism for impairment of ICG retention in patients with CLM.

Methods

Clinicopathologic data of 98 patients with CLM undergoing hepatectomy were analyzed. The archived nontumoral liver parenchyma bearing no CLM were immunostained with CD34 antibody to determine the sinusoidal capillarization.

Results

Of 98 patients, 80 received preoperative chemotherapy. Sinusoidal obstruction syndrome (SOS) occurred in 39 patients (39.8%). The development of SOS in patients receiving oxaliplatin-based chemotherapy was significantly higher compared to those receiving non-oxaliplatin-based chemotherapy (P = 0.003). SOS was independently associated with abnormal ICG retention rate at 15 minutes (ICG-R15) (odds ratio 3.45, 95% confidence interval 1.31–9.04, P = 0.012) and CD 34 overexpression (odds ratio 18.76, 95% confidence interval 4.58–76.81, P < 0.001). ICG-R15 correlated with CD34 expression within the nontumoral liver parenchyma (r = 0.707, P < 0.001) and severity of SOS (r = 0.423, P < 0.001). CD34 positive areas were likely situated at the peripheral area of SOS, and both SOS score and number of cycles of oxaliplatin-based chemotherapy significantly correlated with CD34 expression (r = 0.629, P < 0.001 and r = 0.522, P < 0.001, respectively).

Conclusions

These results suggest that the deterioration of hepatic functional reserve due to SOS is associated with sinusoidal capillarization, indicated by CD34 overexpression within nontumoral liver parenchyma adjacent to SOS.
Literatur
1.
Zurück zum Zitat Adam R. Chemotherapy and surgery: new perspectives on the treatment of unresectable liver metastases. Ann Oncol. 2003; 14(Suppl. 2): 13–6.PubMed Adam R. Chemotherapy and surgery: new perspectives on the treatment of unresectable liver metastases. Ann Oncol. 2003; 14(Suppl. 2): 13–6.PubMed
2.
Zurück zum Zitat Geoghegan JG, Scheele J. Treatment of colorectal liver metastases. Br J Surg. 1999;86:158–69.PubMedCrossRef Geoghegan JG, Scheele J. Treatment of colorectal liver metastases. Br J Surg. 1999;86:158–69.PubMedCrossRef
3.
Zurück zum Zitat Adam R, Delvart V, Pascal G, Valeanu A, Castaing D, Azoulay D, et al. Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival. Ann Surg. 2004;240:644–57.PubMedCrossRef Adam R, Delvart V, Pascal G, Valeanu A, Castaing D, Azoulay D, et al. Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival. Ann Surg. 2004;240:644–57.PubMedCrossRef
4.
Zurück zum Zitat Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, et al. Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. Lancet. 2008;371:1007–16.PubMedCrossRef Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, et al. Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. Lancet. 2008;371:1007–16.PubMedCrossRef
5.
Zurück zum Zitat Adam R, Bhangui P, Poston G, Mirza D, Nuzzo G, Barroso E, et al. Is perioperative chemotherapy useful for solitary, metachronous, colorectal liver metastases? Ann Surg. 2010;252:774–87.PubMedCrossRef Adam R, Bhangui P, Poston G, Mirza D, Nuzzo G, Barroso E, et al. Is perioperative chemotherapy useful for solitary, metachronous, colorectal liver metastases? Ann Surg. 2010;252:774–87.PubMedCrossRef
6.
Zurück zum Zitat Kubota K, Makuuchi M, Kusaka K, Kobayashi T, Miki K, Hasegawa K, et al. Measurement of liver volume and hepatic functional reserve as a guide to decision-making in resectional surgery for hepatic tumors. Hepatology. 1997;26:1176–81.PubMed Kubota K, Makuuchi M, Kusaka K, Kobayashi T, Miki K, Hasegawa K, et al. Measurement of liver volume and hepatic functional reserve as a guide to decision-making in resectional surgery for hepatic tumors. Hepatology. 1997;26:1176–81.PubMed
7.
Zurück zum Zitat Seyama Y, Kokudo N. Assessment of liver function for safe hepatic resection. Hepatol Res. 2009;39:107–16.PubMedCrossRef Seyama Y, Kokudo N. Assessment of liver function for safe hepatic resection. Hepatol Res. 2009;39:107–16.PubMedCrossRef
8.
Zurück zum Zitat Wisse E, De Zanger RB, Charels K, Van Der Smissen P, McCuskey RS. The liver sieve: considerations concerning the structure and function of endothelial fenestrae, the sinusoidal wall and the space of Disse. Hepatology. 1985;5:683–92.PubMedCrossRef Wisse E, De Zanger RB, Charels K, Van Der Smissen P, McCuskey RS. The liver sieve: considerations concerning the structure and function of endothelial fenestrae, the sinusoidal wall and the space of Disse. Hepatology. 1985;5:683–92.PubMedCrossRef
9.
Zurück zum Zitat Fina L, Molgaard HV, Robertson D, Bradley NJ, Monaghan P, Delia D, et al. Expression of the CD34 gene in vascular endothelial cells. Blood. 1990;75:2417–26.PubMed Fina L, Molgaard HV, Robertson D, Bradley NJ, Monaghan P, Delia D, et al. Expression of the CD34 gene in vascular endothelial cells. Blood. 1990;75:2417–26.PubMed
10.
Zurück zum Zitat Couvelard A, Scoazec JY, Dauge MC, Bringuier AF, Potet F, Feldmann G. Structural and functional differentiation of sinusoidal endothelial cells during liver organogenesis in humans. Blood. 1996;87:4568–80.PubMed Couvelard A, Scoazec JY, Dauge MC, Bringuier AF, Potet F, Feldmann G. Structural and functional differentiation of sinusoidal endothelial cells during liver organogenesis in humans. Blood. 1996;87:4568–80.PubMed
11.
Zurück zum Zitat Kuntz E, Kuntz HD. Hepatology: textbook and atlas: history, morphology, biochemistry, diagnostics, clinic, therapy, 3rd edn. Heidelberg: Springer-Verlag; 2008. Kuntz E, Kuntz HD. Hepatology: textbook and atlas: history, morphology, biochemistry, diagnostics, clinic, therapy, 3rd edn. Heidelberg: Springer-Verlag; 2008.
12.
Zurück zum Zitat Takamoto T, Hashimoto T, Sano K, Maruyama Y, Inoue K, Ogata S, et al. Recovery of liver function after the cessation of preoperative chemotherapy for colorectal liver metastasis. Ann Surg Oncol. 2010;17:2747–55.PubMedCrossRef Takamoto T, Hashimoto T, Sano K, Maruyama Y, Inoue K, Ogata S, et al. Recovery of liver function after the cessation of preoperative chemotherapy for colorectal liver metastasis. Ann Surg Oncol. 2010;17:2747–55.PubMedCrossRef
13.
Zurück zum Zitat Nakano H, Oussoultzoglou E, Rosso E, Casnedi S, Chenard-Neu MP, Dufour P, et al. Sinusoidal injury increases morbidity after major hepatectomy in patients with colorectal liver metastases receiving preoperative chemotherapy. Ann Surg. 2008;247:118–24.PubMedCrossRef Nakano H, Oussoultzoglou E, Rosso E, Casnedi S, Chenard-Neu MP, Dufour P, et al. Sinusoidal injury increases morbidity after major hepatectomy in patients with colorectal liver metastases receiving preoperative chemotherapy. Ann Surg. 2008;247:118–24.PubMedCrossRef
14.
Zurück zum Zitat Narita M, Oussoultzoglou E, Chenard MP, Rosso E, Casnedi S, Pessaux P, et al. Sinusoidal obstruction syndrome compromises liver regeneration in patients undergoing two-stage hepatectomy with portal vein embolization. Surg Today. 2011;41:7–17.PubMedCrossRef Narita M, Oussoultzoglou E, Chenard MP, Rosso E, Casnedi S, Pessaux P, et al. Sinusoidal obstruction syndrome compromises liver regeneration in patients undergoing two-stage hepatectomy with portal vein embolization. Surg Today. 2011;41:7–17.PubMedCrossRef
15.
Zurück zum Zitat Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92:205–16. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92:205–16.
16.
Zurück zum Zitat Rahbari NN, Garden OJ, Padbury R, Brooke-Smith M, Crawford M, Adam R, et al. Posthepatectomy liver failure: a definition and grading by the International Study Group of Liver Surgery (ISGLS). Surgery. 2011;149:713–24.PubMedCrossRef Rahbari NN, Garden OJ, Padbury R, Brooke-Smith M, Crawford M, Adam R, et al. Posthepatectomy liver failure: a definition and grading by the International Study Group of Liver Surgery (ISGLS). Surgery. 2011;149:713–24.PubMedCrossRef
17.
Zurück zum Zitat Rubbia-Brandt L, Audard V, Sartoretti P, Roth AD, Brezault C, Le Charpentier M, et al. Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Ann Oncol. 2004;15:460–6.PubMedCrossRef Rubbia-Brandt L, Audard V, Sartoretti P, Roth AD, Brezault C, Le Charpentier M, et al. Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Ann Oncol. 2004;15:460–6.PubMedCrossRef
18.
Zurück zum Zitat Schneider PD. Preoperative assessment of liver function. Surg Clin North Am. 2004;84:355–73.PubMedCrossRef Schneider PD. Preoperative assessment of liver function. Surg Clin North Am. 2004;84:355–73.PubMedCrossRef
19.
Zurück zum Zitat Oussoultzoglou E, Jaeck D, Addeo P, Fuchshuber P, Marzano E, Rosso E, et al. Prediction of mortality rate after major hepatectomy in patients without cirrhosis. Arch Surg. 2010;145:1075–81.PubMedCrossRef Oussoultzoglou E, Jaeck D, Addeo P, Fuchshuber P, Marzano E, Rosso E, et al. Prediction of mortality rate after major hepatectomy in patients without cirrhosis. Arch Surg. 2010;145:1075–81.PubMedCrossRef
20.
Zurück zum Zitat Yokoyama Y, Nishio H, Ebata T, Igami T, Sugawara G, Nagino M. Value of indocyanine green clearance of the future liver remnant in predicting outcome after resection for biliary cancer. Br J Surg. 2010;97:1260–8.PubMedCrossRef Yokoyama Y, Nishio H, Ebata T, Igami T, Sugawara G, Nagino M. Value of indocyanine green clearance of the future liver remnant in predicting outcome after resection for biliary cancer. Br J Surg. 2010;97:1260–8.PubMedCrossRef
21.
Zurück zum Zitat Imamura H, Seyama Y, Kokudo N, Maema A, Sugawara Y, Sano K, et al. One thousand fifty-six hepatectomies without mortality in 8 years. Arch Surg. 2003;138:1198–206.PubMedCrossRef Imamura H, Seyama Y, Kokudo N, Maema A, Sugawara Y, Sano K, et al. One thousand fifty-six hepatectomies without mortality in 8 years. Arch Surg. 2003;138:1198–206.PubMedCrossRef
22.
Zurück zum Zitat Levesque E, Saliba F, Benhamida S, Ichai P, Azoulay D, Adam R, et al. Plasma disappearance rate of indocyanine green: a tool to evaluate early graft outcome after liver transplantation. Liver Transpl. 2009;15:1358–64.PubMedCrossRef Levesque E, Saliba F, Benhamida S, Ichai P, Azoulay D, Adam R, et al. Plasma disappearance rate of indocyanine green: a tool to evaluate early graft outcome after liver transplantation. Liver Transpl. 2009;15:1358–64.PubMedCrossRef
23.
Zurück zum Zitat Poon RT, Fan ST. Assessment of hepatic reserve for indication of hepatic resection: how I do it. J Hepatobiliary Pancreat Surg. 2005;12:31–7.PubMedCrossRef Poon RT, Fan ST. Assessment of hepatic reserve for indication of hepatic resection: how I do it. J Hepatobiliary Pancreat Surg. 2005;12:31–7.PubMedCrossRef
24.
Zurück zum Zitat Hemming AW, Scudamore CH, Shackleton CR, Pudek M, Erb SR. Indocyanine green clearance as a predictor of successful hepatic resection in cirrhotic patients. Am J Surg. 1992;163:515–8.PubMedCrossRef Hemming AW, Scudamore CH, Shackleton CR, Pudek M, Erb SR. Indocyanine green clearance as a predictor of successful hepatic resection in cirrhotic patients. Am J Surg. 1992;163:515–8.PubMedCrossRef
25.
Zurück zum Zitat Krieger PM, Tamandl D, Herberger B, Faybik P, Fleischmann E, Maresch J, et al. Evaluation of chemotherapy-associated liver injury in patients with colorectal cancer liver metastases using indocyanine green clearance testing. Ann Surg Oncol. 2011;18:1644–50.PubMedCrossRef Krieger PM, Tamandl D, Herberger B, Faybik P, Fleischmann E, Maresch J, et al. Evaluation of chemotherapy-associated liver injury in patients with colorectal cancer liver metastases using indocyanine green clearance testing. Ann Surg Oncol. 2011;18:1644–50.PubMedCrossRef
26.
27.
Zurück zum Zitat Hickey PL, McLean AJ, Angus PW, Choo EF, Morgan DJ. Increased sensitivity of propranolol clearance to reduced oxygen delivery in the isolated perfused cirrhotic rat liver. Gastroenterology. 1996;111:1039–48.PubMedCrossRef Hickey PL, McLean AJ, Angus PW, Choo EF, Morgan DJ. Increased sensitivity of propranolol clearance to reduced oxygen delivery in the isolated perfused cirrhotic rat liver. Gastroenterology. 1996;111:1039–48.PubMedCrossRef
28.
Zurück zum Zitat Schaffner F, Poper H. Capillarization of hepatic sinusoids in man. Gastroenterology. 1963;44:239–42.PubMed Schaffner F, Poper H. Capillarization of hepatic sinusoids in man. Gastroenterology. 1963;44:239–42.PubMed
29.
Zurück zum Zitat Haaz MC, Rivory L, Riche C, Vernillet L, Robert J. Metabolism of irinotecan (CPT-11) by human hepatic microsomes: participation of cytochrome P-450 3A and drug interactions. Cancer Res. 1998;58:468–72.PubMed Haaz MC, Rivory L, Riche C, Vernillet L, Robert J. Metabolism of irinotecan (CPT-11) by human hepatic microsomes: participation of cytochrome P-450 3A and drug interactions. Cancer Res. 1998;58:468–72.PubMed
30.
Zurück zum Zitat Schiffer E, Frossard JL, Rubbia-Brandt L, Mentha G, Pastor CM. Hepatic regeneration is decreased in a rat model of sinusoidal obstruction syndrome. J Surg Oncol. 2009;99:439–46.PubMedCrossRef Schiffer E, Frossard JL, Rubbia-Brandt L, Mentha G, Pastor CM. Hepatic regeneration is decreased in a rat model of sinusoidal obstruction syndrome. J Surg Oncol. 2009;99:439–46.PubMedCrossRef
31.
Zurück zum Zitat Wang X, Kanel GC, DeLeve LD. Support of sinusoidal endothelial cell glutathione prevents hepatic veno-occlusive disease in the rat. Hepatology. 2000;31:428–34.PubMedCrossRef Wang X, Kanel GC, DeLeve LD. Support of sinusoidal endothelial cell glutathione prevents hepatic veno-occlusive disease in the rat. Hepatology. 2000;31:428–34.PubMedCrossRef
32.
Zurück zum Zitat Ribero D, Wang H, Donadon M, Zorzi D, Thomas MB, Eng C, et al. Bevacizumab improves pathologic response and protects against hepatic injury in patients treated with oxaliplatin-based chemotherapy for colorectal liver metastases. Cancer. 2007;110:2761–7.PubMedCrossRef Ribero D, Wang H, Donadon M, Zorzi D, Thomas MB, Eng C, et al. Bevacizumab improves pathologic response and protects against hepatic injury in patients treated with oxaliplatin-based chemotherapy for colorectal liver metastases. Cancer. 2007;110:2761–7.PubMedCrossRef
33.
Zurück zum Zitat Narita M, Hatano E, Ikai I, Miyagawa-Hayashino A, Yanagida A, Nagata H, et al. A phosphodiesterase III inhibitor protects rat liver from sinusoidal obstruction syndrome through heme oxygenase-1 induction. Ann Surg. 2009;249:806–13.PubMedCrossRef Narita M, Hatano E, Ikai I, Miyagawa-Hayashino A, Yanagida A, Nagata H, et al. A phosphodiesterase III inhibitor protects rat liver from sinusoidal obstruction syndrome through heme oxygenase-1 induction. Ann Surg. 2009;249:806–13.PubMedCrossRef
34.
Zurück zum Zitat Le Couteur DG, Fraser R, Cogger VC, McLean AJ. Hepatic pseudocapillarisation and atherosclerosis in ageing. Lancet. 2002;359:1612–5.PubMedCrossRef Le Couteur DG, Fraser R, Cogger VC, McLean AJ. Hepatic pseudocapillarisation and atherosclerosis in ageing. Lancet. 2002;359:1612–5.PubMedCrossRef
35.
Zurück zum Zitat Narita M, Hatano E, Tamaki N, Yamanaka K, Yanagida A, Nagata H, et al. Dai-kenchu-to attenuates rat sinusoidal obstruction syndrome by inhibiting the accumulation of neutrophils in the liver. J Gastroenterol Hepatol. 2009;24:1051–7.PubMedCrossRef Narita M, Hatano E, Tamaki N, Yamanaka K, Yanagida A, Nagata H, et al. Dai-kenchu-to attenuates rat sinusoidal obstruction syndrome by inhibiting the accumulation of neutrophils in the liver. J Gastroenterol Hepatol. 2009;24:1051–7.PubMedCrossRef
Metadaten
Titel
Liver Injury Due to Chemotherapy-induced Sinusoidal Obstruction Syndrome Is Associated with Sinusoidal Capillarization
verfasst von
Masato Narita, MD, PhD
Elie Oussoultzoglou, MD
Marie-Pierre Chenard, MD, PhD
Pascal Fuchshuber, MD, PhD, FACS
Muddasar Rather, MD
Edoardo Rosso, MD
Pietro Addeo, MD
Daniel Jaeck, MD, PhD, FRCS
Philippe Bachellier, MD, PhD
Publikationsdatum
01.07.2012
Verlag
Springer-Verlag
Erschienen in
Annals of Surgical Oncology / Ausgabe 7/2012
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-011-2112-6

Weitere Artikel der Ausgabe 7/2012

Annals of Surgical Oncology 7/2012 Zur Ausgabe

Echinokokkose medikamentös behandeln oder operieren?

06.05.2024 DCK 2024 Kongressbericht

Die Therapie von Echinokokkosen sollte immer in spezialisierten Zentren erfolgen. Eine symptomlose Echinokokkose kann – egal ob von Hunde- oder Fuchsbandwurm ausgelöst – konservativ erfolgen. Wenn eine Op. nötig ist, kann es sinnvoll sein, vorher Zysten zu leeren und zu desinfizieren. 

Recycling im OP – möglich, aber teuer

05.05.2024 DCK 2024 Kongressbericht

Auch wenn sich Krankenhäuser nachhaltig und grün geben – sie tragen aktuell erheblich zu den CO2-Emissionen bei und produzieren jede Menge Müll. Ein Pilotprojekt aus Bonn zeigt, dass viele Op.-Abfälle wiederverwertet werden können.

Im OP der Zukunft läuft nichts mehr ohne Kollege Roboter

04.05.2024 DCK 2024 Kongressbericht

Der OP in der Zukunft wird mit weniger Personal auskommen – nicht, weil die Technik das medizinische Fachpersonal verdrängt, sondern weil der Personalmangel es nötig macht.

Nur selten Nachblutungen nach Abszesstonsillektomie

03.05.2024 Tonsillektomie Nachrichten

In einer Metaanalyse von 18 Studien war die Rate von Nachblutungen nach einer Abszesstonsillektomie mit weniger als 7% recht niedrig. Nur rund 2% der Behandelten mussten nachoperiert werden. Die Therapie scheint damit recht sicher zu sein.

Update Chirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

Karpaltunnelsyndrom BDC Leitlinien Webinare
CME: 2 Punkte

Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis
Berufsverband der Deutschen Chirurgie e.V.

S2e-Leitlinie „Distale Radiusfraktur“

Radiusfraktur BDC Leitlinien Webinare
CME: 2 Punkte

Das Webinar beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske
Dr. med. Benjamin Meyknecht
Berufsverband der Deutschen Chirurgie e.V.

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

Appendizitis BDC Leitlinien Webinare
CME: 2 Punkte

Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric
Berufsverband der Deutschen Chirurgie e.V.