Zentralbl Chir 2009; 134(2): 127-135
DOI: 10.1055/s-0028-1098881
Originalarbeit

© Georg Thieme Verlag Stuttgart ˙ New York

Leberresektion beim Hepatozellulären Karzinom – Eigene Ergebnisse und Literaturübersicht

Hepatic Resection for Hepatocellular Carcinoma – Results and Analysis of the Current LiteratureH. Neeff1 , F. Makowiec1 , J. Harder2 , V. Gumpp3 , A. Klock1 , R. Thimme2 , O. Drognitz1 , U. T. Hopt1
  • 1Universität Freiburg, Allgemein- und Viszeralchirurgie, Freiburg, Germany
  • 2Universität Freiburg, Innere Medizin II, Freiburg, Germany
  • 3Universität Freiburg, Comprehensive Cancer Center, Freiburg, Germany
Further Information

Publication History

Publication Date:
20 April 2009 (online)

Zusammenfassung

Hintergrund: Das hepatozelluläre Karzinom (HCC) ist weltweit die fünft häufigste Krebstodes­ursache. In Mitteleuropa ist seine Inzidenz zwar deutlich niedriger, aber stetig zunehmend. Hier spielen weniger virale Grunderkrankungen als nutritiv-toxische / metabolische Ursachen (Alkohol, Diabetes, Übergewicht) eine Rolle. Die Therapiemöglichkeiten des HCC sind stark abhängig vom Ausmaß der Erkrankung bei der Diagnosestellung und umfassen, neben lokal destruierenden Verfahren, die Lebertransplantation sowie die chirurgische Resektion. In dieser Arbeit sollen aktuelle Ergebnisse der Resektion des HCC vorgestellt und mit Ergebnissen sowohl der Resektion aber auch der lokalen Therapie und Transplanta­tion verglichen werden. Patienten: Von 1999–2008 führten wir bei 93 Patienten (83 % männlich, medianes Alter 64 [Spanne 39–94] Jahre) eine Leberresektion wegen eines HCC durch. Die Datenerhebung erfolgte prospektiv. Die für 85 Patienten erhältliche Nachbeobachtungszeit lag im Median bei 1,2 Jahren (0,25–8 Jahre). Ergebnisse: Im Gegensatz zur weltweiten Epi­demiologie des HCC wurde eine virale Hepatitis als Grunderkrankung nur bei 28 % aller Patienten nachgewiesen. Eine Zirrhose lag in 50 % vor. Die Anzahl der Tumore betrug im Median eins (1–11). Die mediane Tumorgröße lag bei 55 mm (5–250 mm). 58 % der Tumore wurden atypisch oder durch Segmentresektion, 42 % durch eine (ggf. erweiterte) Hemihepatektomie entfernt. In 95 % gelang die R0-Resektion. Die Gesamtkomplikationsrate lag bei 61 %. Eine operative Revision wurde in 10 % durchgeführt. Die Gesamtmortalität lag bei 8,6 % und nahm während des Studienzeitraumes stark ab (1999–2004: 14,9 %, 2005–2008: 2,2 %, p = 0,03). Das kumulative Überleben betrug 81 % nach 1 Jahr, 58 % nach 3 Jahren und 26 % nach 5 Jahren. Als tendenzieller prognostischer Faktor konnte das T-Stadium identifiziert werden. Schlussfolgerung: Die Resektion hepatozellulärer Karzinome ist neben lokal ablativen Verfahren und der Transplantation eine der Haupttherapieoptionen. Eine sorgfältige Patientenselektion lässt R0-Resektionsraten > 90 % zu. Trotz einer hohen Gesamtkomplikationsrate bleibt die Notwendigkeit einer Re-Operation eher die Ausnahme. Die perioperative Mortalität nahm in der zweiten Hälfte des Untersuchungszeitraumes zwar signifikant ab, lag aber insgesamt mit 8,6 % höher als nach Resektion anderer Lebertumore. Die Überlebensrate unserer Serie ist vergleichbar mit Berichten anderer europäischen Zentren.

Abstract

Background: Hepatocellular carcinoma (HCC) is the fifth-leading cause of cancer death world­wide. Although less frequent in Western Europe, its incidence is increasing in this region. Causes involved in the pathogenesis of HCC are, besides viral hepatitis, metabolic and nutritional factors (alcohol, diabetes, obesity). The therapeutic man­agement depends strongly on the initial extent of disease and includes hepatic resection, liver transplantation and local ablation. In this context, we present our results on liver resection for HCC and a discussion of the current literature about (potentially curative) treatment for HCC. Patients: From 1999 until 2008 93 patients [83 % male, median age 64 (range: 39–94) years] underwent hepatic resection for HCC. Postoperative follow-up was available in 85 patients [median follow-up: 1.2 (0.25–8) years]. Results: In contrast to data, especially from Asia, a viral hepatitis as the origin of HCC was found in only 28 % of the patients in our series. Half of the patients had proven liver cirrhosis. The median number of intrahepatic tumours was one (1–11), median size of the largest tumour was 55 mm (5–250 mm). 58 % of the HCC were removed by ­atyp­ical or segmental resection, 42 % of the pa­tients underwent hemihepatectomy or extended ­hemihepatectomy. Tumor-free resection margins were ­achieved in 95 %. Total postoperative morbidity was 61 %. A reoperation for complications was ­necessary in 10 %. Hospital mortality was 8.6 % in the entire study period but decreased from 14.9 % in 1999–2004 to 2.2 % in 2005 to 2008 (p = 0.03). Actuarial survival was 81 % after 1 year, 58 % after 3 years and 26 % after 5 years. The T-stage could be identified tendentially as a prognostic factor influencing survival. Conclusion: With the proper selection of patients, liver resection for HCC may be performed with a curative intention (i. e., free resection margins) in over 90 %. Although it decreased during the study period peri­operative mortality was higher than after resection of other hepatic tumours. Long-term survival in our series was comparable to reports from other European centres.

Literatur

  • 1 Bosch F X, Ribes J, Díaz M et al. Primary liver cancer: Worldwide incidence and trends.  Gastroenterology. 2004;  127 5-16
  • 2 McGlynn K A, Tsao L, Hsing A W et al. International trends and patterns of primary liver cancer.  Int J Cancer. 2001;  94 290-296
  • 3 Ferlay J, Autier P, Boniol M et al. Estimates of the cancer incidence and mortality in Europe in 2006.  Ann Oncol. 2007;  18 581-592
  • 4 Marrero J A, Fontana R J, Fu S et al. Alcohol, tobacco and obesity are ­synergistic risk factors for hepatocellular carcinoma.  J Hepatol. 2005;  42 218-224
  • 5 El-Serag H B, Tran T, Everhart J E. Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma.  Gastroenterology. 2004;  126 460-468
  • 6 Hashimoto E, Yatsuji S, Tobari M et al. Hepatocellular carcinoma in ­patients with nonalcoholic steatohepatitis.  J Gastroenterol. 2009;  44 89-95
  • 7 Caldwell S H, Crespo D M, Kang H S et al. Obesity and hepatocellular carcinoma.  Gastroenterology. 2004;  127 97-103
  • 8 Blum H E. Epidemiologie, Diagnostik und Prävention.  Der Gastroente­rologe. 2007;  2 6-11
  • 9 Borie F, Bouvier A M, Herrero A et al. Treatment and prognosis of hepatocellular carcinoma: A population based study in France.  J Surg Oncol. 2008;  98 505-509
  • 10 Kanzler S, Teufel A, Galle P R. Liver function test to predict hepatic failure after liver resection – expensive and without clinical relevance?.  Zentralbl Chir. 2007;  132 267-273
  • 11 Lau W Y, Lai E C. Hepatocellular carcinoma: Current management and recent advances.  Hepatobiliary Pancreat Dis Int. 2008;  7 237-257
  • 12 Fong Y, Sun R L, Jarnagin W et al. An analysis of 412 cases of hepatocellular carcinoma at a Western center.  Ann Surg. 1999;  229 790-800
  • 13 Spangenberg H C. Lokal-ablative Therapie.  Der Gastroenterologe. 2007;  2 27-33
  • 14 Lopez P M, Villanueva A, Llovet J M. Systematic review: Evidence-Based management of hepatocellular carcinoma – an updated analysis of randomized controlled trials.  Aliment Pharmacol Ther. 2006;  23 1535-1547
  • 15 Lencioni R, Crocetti L. A critical appraisal of the literature on local ­ablative therapies for hepatocellular carcinoma.  Clin Liver Dis. 2005;  9 301-314
  • 16 Lau W Y, Lai E C. The current role of radiofrequency ablation in the management of hepatocellular carcinoma: A systematic review.  Ann Surg. 2009;  249 20-25
  • 17 Grundmann R T, Hermanek P, Merkel S et al. Diagnosis and treatment of colorectal liver metastases – workflow.  Zentralbl Chir. 2008;  133 267-284
  • 18 Edmondson H A, Steiner P E. Primary carcinoma of the liver: A study of 100 cases among 48 900 necropsies.  Cancer. 1954;  7 462-503
  • 19 Couinaud C. Anatomic principles of left and right regulated hepatec­tomy: Technics.  J Chir (Paris). 1954;  70 933-966
  • 20 Vauthey J N, Abdalla E K, Doherty D A et al. Body surface area and body weight predict total liver volume in Western adults.  Liver Transpl. 2002;  8 233-240
  • 21 El-Serag H B, Siegel A B, Davila J A et al. Treatment and outcomes of treating of hepatocellular carcinoma among Medicare recipients in the United States: A population-based study.  J Hepatol. 2006;  44 158-166
  • 22 Samuel M, Chow P K, Chan Shih-Yen E et al. Neoadjuvant and adjuvant therapy for surgical resection of hepatocellular carcinoma. Cochrane Database Syst Rev 2009; 1: CD001199
  • 23 Sotiropoulos G C, Lang H, Frilling A et al. Resectability of hepatocellular carcinoma: Evaluation of 333 consecutive cases at a single hepatobiliary specialty center and systematic review of the literature.  Hepatogastroenterology. 2006;  53 322-329
  • 24 Okuda K, Ohtsuki T, Obata H et al. Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients.  Cancer. 1985;  56 918-928
  • 25 Dohmen K. Many staging systems for hepatocellular carcinoma: Evolution from Child-Pugh, Okuda to SLiDe.  J Gastroenterol Hepatol. 2004;  19 1227-1232
  • 26 The Cancer of the Liver Italian Program (CLIP) investigators . Prospective validation of the CLIP score: A new prognostic system for patients with cirrhosis and hepatocellular carcinoma.  Hepatology. 2000;  31 840-845
  • 27 Chevret S, Trinchet J C, Mathieu D et al. A new prognostic classification for predicting survival in patients with hepatocellular carcinoma. Groupe d’etude et de traitement du carcinome hépatocellulaire.  J Hepatol. 1999;  31 133-141
  • 28 Llovet J M, Brú C, Bruix J. Prognosis of hepatocellular carcinoma: The BCLC staging classification.  Semin Liver Dis. 1999;  19 329-338
  • 29 Schöniger-Hekele M, Müller C, Kutilek M et al. Hepatocellular carcinoma in Central Europe: Prognostic features and survival.  Gut. 2001;  48 103-109
  • 30 Leung T W, Tang A M, Zee B et al. Construction of the Chinese University Prognostic Index for hepatocellular carcinoma and comparison with the TNM staging system, the Okuda staging system, and the Cancer of the Liver Italian Program staging system: A study based on 926 patients.  Cancer. 2002;  94 1760-1769
  • 31 Kudo M, Chung H, Osaki Y. Prognostic staging system for hepatocellular carcinoma (CLIP score): Its value and limitations, and a proposal for a new staging system, the Japan Integrated Staging Score (JIS score).  J Gastroenterol. 2003;  38 207-215
  • 32 Omagari K, Honda S, Kadokawa Y et al. Preliminary analysis of a newly proposed prognostic scoring system (SLiDe score) for hepatocellular carcinoma.  J Gastroenterol Hepatol. 2004;  19 805-811
  • 33 Neuhaus P, Jonas S, Bechstein W O. Hepatoma of the liver – resection or transplantation?.  Langenbecks Arch Surg. 2000;  385 171-178
  • 34 Morris-Stiff G, Gomez D, de Liguori Carino N et al. Surgical management of hepatocellular carcinoma: Is the jury still out?.  Surg Oncol. 2008;  , [Epub ahead of print]
  • 35 Facciuto M E, Koneru B, Rocca J P et al. Surgical treatment of hepato­cellular carcinoma beyond Milan criteria. Results of liver resection, salvage transplantation, and primary liver transplantation.  Ann Surg ­Oncol. 2008;  15 1383-1391
  • 36 Mazzaferro V, Llovet J M, Miceli R et al. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: A retrospective, exploratory analysis.  Lancet Oncol. 2009;  10 35-43
  • 37 Yao F Y, Ferrell L, Bass N M et al. Liver transplantation for hepatocellular carcinoma: Comparison of the proposed UCSF criteria with the Milan criteria and the Pittsburgh modified TNM criteria.  Liver Transpl. 2002;  8 765-774
  • 39 Ladurner R, Königsrainer A. Liver surgery: what is feasible?.  Zentralbl Chir. 2007;  132 274-280
  • 40 Lai E C, Fan S T, Lo C M et al. Hepatic resection for hepatocellular carci­noma. An audit of 343 patients.  Ann Surg. 1995;  221 291-298
  • 41 Song T J, Ip E W, Fong Y. Hepatocellular carcinoma: Current surgical management.  Gastroenterology. 2004;  127 248-260
  • 42 Belghiti J, Regimbeau J M, Durand F et al. Resection of hepatocellular carcinoma: A European experience on 328 cases.  Hepatogastroenterology. 2002;  49 41-46
  • 43 Bège T, Le Treut Y P, Hardwigsen J et al. Prognostic factors after resection for hepatocellular carcinoma in nonfibrotic or moderately fibrotic liver. A 116-case European series.  J Gastrointest Surg. 2007;  11 619-625
  • 44 Jarnagin W R, Gonen M, Fong Y et al. Improvement in perioperative outcome after hepatic resection: Analysis of 1 803 consecutive cases over the past decade.  Ann Surg. 2002;  236 397-406
  • 45 Mullen J T, Ribero D, Reddy S K et al. Hepatic insufficiency and mortality in 1 059 noncirrhotic patients undergoing major hepatectomy.  J Am Coll Surg. 2007;  204 854-862
  • 46 Lang H, Sotiropoulos G C, Dömland M et al. Liver resection for hepatocellular carcinoma in non-cirrhotic liver without underlying viral hepatitis.  Br J Surg. 2005;  92 198-202
  • 47 Lang H, Sotiropoulos G C, Brokalaki E I et al. Survival and recurrence rates after resection for hepatocellular carcinoma in noncirrhotic ­livers.  J Am Coll Surg. 2007;  205 27-36
  • 48 Lubrano J, Huet E, Tsilividis B et al. Long-Term outcome of liver resection for hepatocellular carcinoma in noncirrhotic nonfibrotic liver with no viral hepatitis or alcohol abuse.  World J Surg. 2008;  32 104-109
  • 49 Rayya F, Harms J, Bartels M et al. Results of resection and transplantation for hepatocellular carcinoma in cirrhosis and noncirrhosis.  Transplant Proc. 2008;  40 933-935
  • 50 Tanaka K, Shimada H, Matsumoto C et al. Anatomic versus limited nonanatomic resection for solitary hepatocellular carcinoma.  Surgery. 2008;  143 607-615
  • 51 Portolani N, Coniglio A, Ghidoni S et al. Early and late recurrence after liver resection for hepatocellular carcinoma: Prognostic and thera­peutic implications.  Ann Surg. 2006;  243 229-235
  • 52 Makuuchi M, Sano K. The surgical approach to HCC: Our progress and results in Japan.  Liver Transpl. 2004;  10 46-52
  • 53 Ercolani G, Grazi G L, Ravaioli M et al. Liver resection for hepatocellular carcinoma on cirrhosis: Univariate and multivariate analysis of risk factors for intrahepatic recurrence.  Ann Surg. 2003;  237 536-543
  • 54 Otto G, Heuschen U, Hofmann W J et al. Survival and recurrence after ­liver transplantation versus liver resection for hepatocellular carci­noma: A retrospective analysis.  Ann Surg. 1998;  227 424-432

F. Makowiec

University of Freiburg · Department of Surgery · Freiburg · Germany

Phone: +49 / 7 61 / 2 70 28 06

Fax: +49 / 7 61 / 2 70 28 04

Email: Frank.Makowiec@uniklinik-freiburg.de