Diagnostik und Therapie von Lebermetastasen kolorektaler Karzinome - Workflow

Zusammenfassung

In dieser Übersicht wird zu den Standards der Diagnostik und Therapie von Lebermetastasen kolorektaler Karzinome auf der Basis eines Workshops Stellung genommen. Es werden Algorithmen zum Vorgehen bei Patienten mit synchronen / metachronen kolorektalen Lebermetastasen sowie beim lokoregionären Rezidivtumor beschrieben. Die chirurgische Resektion ist die Methode der Wahl zur kurativen Behandlung von Lebermetastasen. Die Indikation hierzu sollte sich an folgenden Faktoren orientieren:
1. Generelle Operabilität des Patienten (Begleiterkrankung),
2. Erreichbarkeit einer R 0-Situation,
i. ggf. in Kombination mit ablativen Verfahren,
ii. ggf. neoadjuvante Chemotherapie,
iii. Sanierbarkeit extrahepatischer Tumormanifestation,
3. Ausreichende funktionelle Leberreserve nach Erreichen einer R 0-Situation,
i. ggf. Pfortaderembolisation oder zweizeitiges Vorgehen,
4. Zwei benachbarte Lebersegmente können mit vollständiger vaskulärer und biliärer Versorgung erhalten werden,
5. Tumorbiologische Aspekte („prognostische Parameter”),
6. Erfahrung des Chirurgen / Zentrums!
Extrahepatische Metastasen stellen keine absolute Kontraindikation zur Leberresektion dar, vorausgesetzt, eine komplette Resektion von intra- und extrahepatischem Tumor ist möglich. Lässt sich eine R 0-Resektion erreichen, wird selbst bei bilateralem Leberbefall und 5 und mehr Knoten eine sinnvolle Operationsindikation beschrieben. Die Art der Leberresektion (Wedge-Resektion vs. anatomische Resektion) hat keinen Einfluss auf die Rezidivrate. Die präoperative Volumetrie ist bei größeren Resektionen angezeigt. Mindestanforderungen an die Größe der Restleber sind: 25 % des gesunden Lebergewebes bei Patienten mit normaler Leber, bei Zustand nach Zytostatika, Fettleber, Fibrose und Diabetes 40 % und bei Zirrhose 50-60 %. Bei 15-30 % der Patienten, die initial als anatomisch irresektabel gelten, erlaubt die präoperative Chemotherapie eine komplette Resektion, jedoch ist der Nutzen einer neoadjuvanten Chemotherapie bei Patienten mit resektablen Metastasen noch nicht ausreichend belegt. Lokal destruierende Maßnahmen wie Radiofrequenzablation (RFA) oder Laserinduzierte interstitielle Thermotherapie (LITT) kommen vor allem bei zentralen Rezidivmetastasen, risikoreichen Leberresektionen einer Seite (wegen großer oder multipler Metastasen) und gleichzeitig tief liegender Metastase der anderen Seite in Betracht sowie für zwei bis drei kleine Metastasen bei eingeschränkter Operationsfähigkeit. Patienten mit Tumoren größer 3 cm zeigen bei der perkutanen RFA eine hohe lokale Rezidivrate und sind keine optimalen Kandidaten für dieses Verfahren. Sowohl für die operative Behandlung als auch die lokal destruierenden Maßnahmen muss ausreichende Erfahrung vorliegen, sodass diese Patienten nur in Zentren mit Erfahrung in der Leberchirurgie behandelt werden sollten.

Abstract

In this review, standards of diagnosis and treatment of colorectal liver metastases are described on the basis of a workshop discussion. Algorithms of care for patients with synchronous / metachronous colorectal liver metastases or locoregional recurrent tumour are presented. Surgical resection is the procedure of choice in the curative treatment of liver metastases. The decision about the resection of liver metastases should consider the following parameters:
1. General operability of the patient (comorbidity);
2. Achievability of an R 0 situation:
i. if necessary, in combination with ablative methods,
ii. if necessary, neoadjuvant chemotherapy, iii. the ability to eradicate extrahepatic tumour manifestations;
3. Sufficient volume of the liver remaining after resection („future liver remnant = FLR):
i. if necessary, in combination with portal vein embolisation or two-stage hepatectomy;
4. The feasibility to preserve two contiguous hepatic segments with adequate vascular inflow and outflow as well as biliary drainage;
5. Tumour biological aspects (“prognostic variables”);
6. Experience of the surgeon and centre!
Extrahepatic disease does not contraindicate hepatectomy for colorectal liver metastases provided a complete resection of both intra- and extrahepatic disease is feasible. Even in bilobar colorectal metastases and 5 or more tumours in the liver, a complete tumour resection has been described. The type of resection (hepatic wedge resection or anatomic resection) does not influence the recurrence rate. Preoperative volumetry is indicated when major hepatic resection is planned. The FLR should be 25 % in patients with normal liver, 40 % in patients who have received intensive chemotherapy or in cases of fatty liver, liver fibrosis or diabetes, and 50-60 % in patients with cirrhosis. In patients with initially unresectable colorectal liver metastases, preoperative chemotherapy enables complete resection in 15-30 % of the cases, whereas the value of neoadjuvant chemotherapy in patients with resectable liver metastases has not been sufficiently supported. In situ ablative procedures (radiofrequency ablation = RFA and laser-induced interstitial thermotherapy = LITT) are local therapy options in selected patients who are not candidates for resection (central recurrent liver metastases, bilobar multiple metastases and high-risk resection or restricted patient operability). Patients with tumours larger than 3 cm have a high local recurrence rate after percutaneous RFA and are not optimal candidates for this procedure. The physician's experience influences the results significantly, both after hepatectomy and after in situ ablation. Therefore, patients with colorectal liver metastases should be treated in centres with experience in liver surgery.

Schlüsselwörter

Lebermetastasen - kolorektales Karzinom - Leberresektion - Radiofrequenzablation - Laser - Chemotherapie

Key words

liver metastasis - colorectal carcinoma - liver resection - radiofrequency ablation - laser - chemotherapy

Literatur

• 1 Abdalla E K, Barnett C C, Doherty D et al. Extended hepatectomy in patients with hepatobiliary malignancies with and without preoperative portal vein embolization.  Arch Surg. 2002;  137 675-680
• 2 Abdalla E K, Vauthey J-N, Ellis L M et al. Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection / ablation for colorectal liver metastases.  Ann Surg. 2004;  239 818-827
• 3 Abdalla E K, Adam R, Bilchik A J et al. Improving resectability of hepatic colorectal metastases: Expert consensus statement.  Ann Surg Oncol. 2006;  13 1271-1280
• 4 Adam R, Laurent A, Azoulay D et al. Two-stage hepatectomy: a planned strategy to treat unresectable liver tumors.  Ann Surg. 2000;  232 777-785
• 5 Adam R, Avisar E, Ariche A et al. Five-year survival following hepatic resection after neoadjuvant therapy for nonresectable colorectal (liver) metastases.  Ann Surg Oncol. 2001;  8 347-352
• 6 Adam R, Pascal G, Azoulay D et al. Liver resection for colorectal metastases. The third hepatectomy.  Ann Surg. 2003;  238 871-884
• 7 Adam R, Delvart V, Pascal G et al. Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival.  Ann Surg. 2004;  240 644-657
• 8 Adam R, Pascal G, Castaing D et al. Tumor progression while on chemotherapy. A contraindication to liver resection for multiple colorectal metastases?.  Ann Surg. 2004;  240 1052-1064
• 9 Adams R B, Haller D G, Roth M S. Editorial review: Improving resectability of hepatic colorectal metastases: Expert consensus statement by Abdalla et al.  Ann Surg Oncol. 2006;  13 1281-1283
• 10 Ahmad A, Chen S L, Bilchik A J. Role of repeated hepatectomy in the multimodal treatment of hepatic colorectal metastases.  Arch Surg. 2007;  142 526-532
• 11 Alberts S R, Horvath W L, Sternfeld W C et al. Oxaliplatin, fluorouracil and leucovorin for patients with unresectable liver-only metastases from colorectal cancer: a North Central Cancer Treatment Group phase II study.  J Clin Oncol. 2005;  23 9243-9249
• 12 Bartlett D L, Berlin J, Lauwers G Y et al. Chemotherapy and regional therapy of hepatic colorectal metastases: Expert consensus statement.  Ann Surg Oncol. 2006;  13 1284-1292
• 13 Baumann T, Ludwig U, Pache G et al. Detection of pulmonary nodules with move-during-scan MRI using a free-breathing TIRM sequence.  Invest Radiol. 2008;  ,  (ahead of print)
• 14 Bechstein W O, Golling M. Chirurgische Resektion kolorektaler Lebermetastasen. Was ist Standard?.  Chirurg. 2005;  76 543-551
• 15 Benoist S, Brouquet A, Penna C et al. Complete response of colorectal liver metastases after chemotherapy: does it mean cure?.  J Clin Oncol. 2006;  24 3939-3945
• 16 Berufsverband Deutscher Pathologen und Deutsche Gesellschaft für Pathologie .Empfehlungen zur pathologisch-anatomischen Diagnostik des kolorektalen Karzinoms, 2005. Berufsverband Deutscher Pathologen, Gelsenkirchen. www.bv-pathologie.de
• 17 Bipat S, van Leeuwen M S, Comans E FI et al. Colorectal liver metastases: CT, MR imaging and PET for diagnosis - Meta-Analysis.  Radiology. 2005;  237 123-131
• 18 Boige V, Malka D, Elias D et al. Hepatic arterial infusion of oxaliplatin and intravenous LV5FU2 in unresectable liver metastases from colorectal cancer after systemic chemotherapy failure.  Ann Surg Oncol. 2008;  15 219-226
• 19 Bolton J S, Fuhrmann G M. Survival after resection of multiple bilobar hepatic metastases from colorectal carcinoma.  Ann Surg. 2000;  231 743-752
• 20 Brunt E M, Janney C G, Di Bisceglie A M et al. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions.  Am J Gastroenterol. 1999;  94 2467-2474
• 21 Buhr H J, Dommisch K, Fleischer G-M für die Arbeitsgruppe „Workflow Rektumkarzinom” et al.,. Klinischer Ablaufpfad (Workflow) zu Diagnostik, Therapie und Nachsorge des Rektumkarzinoms.  Zentralbl Chir. 2006;  131 285-297
• 22 Capussotti L, Muratore A, Mulas M M et al. Neoadjuvant chemotherapy and resection for initially irresectalbe colorectal liver metastases.  Br J Surg. 2006;  93 1001-1006
• 23 Capussotti L, Vigano L, Ferrero A et al. Timing of liver metastases synchronous to colorectal tumor: Proposal of prognosis-based decisional model.  Ann Surg Oncol. 2007;  14 1143-1150
• 24 Chapman W C, Hoff P M, Strasberg S M. Editorial review: Selection of patients for resection of hepatic colorectal metastases: Expert consensus statement by Charnsangavej et al.  Ann Surg Oncol. 2006;  13 1269-1270
• 25 Chari R S, Helton W S, Marsh R D. Editorial review: chemotherapy and regional therapy of hepatic colorectal metastases: Expert consensus statement by Bartlett et al.  Ann Surg Oncol. 2006;  13 1293-1295
• 26 Charnsangavej C, Clary B, Fong Y et al. Selection of patients for resection of hepatic colorectal metastases: Expert consensus statement.  Ann Surg Oncol. 2006;  13 1261-1268
• 27 Chu Q D, Vezeridis M P, Avradopoulos K A et al. Repeat hepatic resection for recurrent colorectal cancer.  World J Surg. 1997;  21 292-296
• 28 Chun Y S, Vauthey J-N, Ribero D et al. Systemic chemotherapy and two-stage hepatectomy for extensive bilateral colorectal liver metastases: perioperative safety and survival.  J Gastrointest Surg. 2007;  11 1498-1505
• 29 Clavien P-A, Yadav S, Sindram D et al. Protective effects of ischemic preconditioning for liver resection performed under inflow occlusion in humans.  Ann Surg. 2000;  332 155-162
• 30 Clavien P -A, Selzner M, Rüdiger H A et al. A prospective randomized study in 100 consecutive patients undergoing major liver resection with versus without ischemic precondition.  Ann Surg. 2003;  238 843-852
• 31 Clavien P-A, Petrowsky H, DeOliveira M et al. Strategies for safer liver surgery and partial liver transplantation.  N Engl J Med. 2007;  356 1545-1549
• 32 Dawson L, McGinn C J, Normolle D et al. Escalated focal liver radiation and concurrent hepatic artery fluorodeoxyuridine for unresectable intrahepatic malignancies.  J Clin Oncol. 2000;  18 2210-2218
• 33 Ducreux M, Ychou M, Laplanche A et al. Hepatic arterial oxaliplatin infusion plus intravenous chemotherapy in colorectal cancer with inoperable hepatic metastases: A trial of the Gastrointestinal Group of the Féderation Nationale des Centres de Lutte Contre le Cancer.  J Clin Oncol. 2005;  23 4881-4887
• 34 Dworak O, Keilholz L, Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy.  Int J Colorect Dis. 1997;  12 19-23
• 35 Elias D, Cavalcanti A, de Baere T et al. [Long-term oncological results of hepatectomy performed after selective portal emoblization].  Ann Chir. 1999;  53 559-564
• 36 Elias D, Quellet J-F, Bellon N et al. Extrahepatic disease does not contraindicate hepatectomy for colorectal liver metastases.  Br J Surg. 2003;  90 567-574
• 37 Elias D, Baton O, Sideris L et al. Local recurrences after intraoperative radiofrequency ablation of liver metastases: a comparative study with anatomic and wedge resections.  Ann Surg Oncol. 2004;  11 500-505
• 38 Elias D, Goere D, Boige V et al. Outcome of posthepatectomy-missing colorectal liver metastases after complete response to chemotherapy: Impact of adjuvant intra-arterial hepatic oxaliplatin.  Ann Surg Oncol. 2007;  14 3188-3194
• 39 Evrard S, Becouarn Y, Fonck M et al. Surgical treatment of liver metastases by radiofrequency ablation, resection, or in combination.  Eur J Surg Oncol. 2004;  30 399-406
• 40 Falcone A, Ricci S, Brunetti I et al. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest.  J Clin Oncol. 2007;  25 1670-1676
• 41 Fautz H-P, Kannengiesser S AR. Sliding multislice (SMS): a new technique for minimum FOV usage in axial continuously moving-table acquisitions.  Magn Res Med. 2006;  55 363-370
• 42 Fernandez F G, Ritter J, Wendell Goodwich J et al. Effect of steatohepatitis associated with irinotecan or oxaliplatin pretreatment on resectability of hepatic colorectal metastases.  J Am Coll Surg. 2005;  200 845-853
• 43 Fernández-Trigo V, Shamsa F, Sugarbaker P H. and other members of the Repeat Hepatic Metastases Registry . Repeat liver resections from colorectal metastasis.  Surgery. 1995;  117 296-304
• 44 Figueras J, Torras J, Valls C et al. Surgical resection of colorectal liver metastases in patients with expanded indications: a single-center experience with 501 patients.  Dis Colon Rectum. 2007;  50 478-488
• 45 Fong Y, Fortner J, Sun R L et al. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer. Analysis of 1001 consecutive cases.  Ann Surg. 1999;  230 309-318
• 46 Gallagher D J, Capanu M, Raggio G et al. Hepatic arterial infusion plus systemic irinotecan in patients with unresectable hepatic metastases from colorectal cancer previously treated with systemic oxaliplatin: a retrospective analysis.  Ann Oncol. 2007;  18 1995-1999
• 47 Germer C -T, Buhr H J, Isbert C. Nichtoperative Ablation. Möglichkeiten und Grenzen der Ablationsverfahren zur Behandlung von Lebermetastasen unter kurativer Intention.  Chirurg. 2005;  76 552-562
• 48 Gruttadauria S, Luca A, Mandala' L et al. Sequential preoperative ipsilateral portal and arterial embolization in patients with colorectal liver metastases.  World J Surg. 2006;  30 576-578
• 49 Herfarth K K, Debus J. Stereotaktische Strahlentherapie von Lebermetastasen.  Chirurg. 2005;  76 564-569
• 50 Hermanek P. Liver metastases: Classification and staging systems.  Hepato-Gastroenterol 39, Eur Clin Digest Dis Suppl. 1992;  1 10-37
• 51 Hildebrandt B, Pech M, Nicolaou E et al. Interventionally implanted port catheter systems for hepatic arterial infusion of chemotherapy in patients with colorectal liver metastases: a phase II study and historical comparison with the surgical approach.  BMC Cancer. 2007;  7 69
• 52 Ho W M, Ma B, Mok T et al. Liver resection after irinotecan, 5-fluorouracil, and folinic acid for patients with unresectable colorectal liver metastases: a multicenter phase II study by the Cancer Therapeutic Research Group.  Med Oncol. 2005;  22 203-212
• 53 Isbert C, Buhr H J, Ritz J-P et al. Curative in situ ablation of colorectal liver metastases - experimental and clinical implementation.  Int J Colorect Dis. 2007;  22 705-715
• 54 Jaeck D, Nakano H, Bachellier P et al. Significance of hepatic pedicle lymph node involvement in patients with colorectal liver metastases: a prospective study.  Ann Surg Oncol. 2002;  9 430-438
• 55 Jaeck D, Bachellier P, Nakano H et al. One or two-stage hepatectomy combined with portal vein embolization for initially nonresectable colorectal liver metastases.  Am J Surg. 2003;  185 221-229
• 56 Jaeck D, Oussoultzoglou E, Rosso E et al. A two-stage hepatectomy procedure combined with portal vein embolization to achieve curative resection for initially unresectable multiple and bilobar colorectal liver metastases.  Ann Surg. 2004;  240 1037-1051
• 57 Junginger T, Kneist W, Dünschede F et al. Lebermetastasen kolorektaler Karzinome - wie oft kann man operieren?.  Zentralbl Chir. 2007;  132 281-286
• 58 Kaido T, Arii S, Shimada Y et al. Portal embolization in various types of liver: novel variables to predict hypertrophy.  Hepatogastroenterology. 2003;  50 140-145
• 59 Kanzler S, Teufel A, Galle P R. Funktionsdiagnostik vor Leberresektionen - teuer und ohne klinische Relevanz?.  Zentralbl Chir. 2007;  132 267-273
• 60 Karoui M, Penna C, Amin-Hashem M et al. Influence of preoperative chemotherapy on the risk of major hepatectomy for colorectal liver metastases.  Ann Surg. 2006;  243 1-7
• 61 Kavanagh B D, Schefter T E, Cardenes H R et al. Interim analysis of a prospective phase I / II trial of SBRT for liver metastases.  Acta Oncol. 2006;  45 848-855
• 62 Kemeny N, Huang Y, Cohen A M et al. Hepatic arterial infusion of chemotherapy after resection of hepatic metastases from colorectal cancer.  New Engl J Med. 1999;  341 2039-2048
• 63 Kemeny N E, Gonen M. Hepatic arterial infusion after liver resection.  N Engl J Med. 2005;  352 734-735
• 64 Kennedy A S, Coldwell D, Nutting C et al. Resin ⁹⁰Y-microsphere brachytherapy for unresectable colorectal liver metastases: modern USA experience.  Int J Radiat Oncol Biol Phys. 2006;  65 412-425
• 65 Khan A Z, Karanjia N D. The impact of staging laparoscopy prior to hepatic resection for colorectal metastases.  Eur J Surg Oncol. 2007;  33 1010-1013
• 66 Kin T, Nakajima Y, Kanehiro H et al. Repeat hepatectomy for recurrent colorectal metastases.  World J Surg. 1998;  22 1087-1091
• 67 Kleiner D E, Brunt E M, Van Natta M for the Nonalcoholic Steatohepatitis Clinical Research Network et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease.  Hepatology. 2005;  41 1313-21
• 68 Kobayashi K, Kawamura M, Ishihara T. Surgical treatment for both pulmonary and hepatic metastases from colorectal cancer.  J Thorac Cardiovasc Surg. 1999;  118 1090-1096
• 69 Koffron A J, Auffenberg G, Kung R et al. Evaluation of 300 minimally invasive liver resections at a single institution. Less is more.  Ann Surg. 2007;  246 385-394
• 70 Kune G A, Kune S, Field B et al. Survival in patients with large-bowel cancer. A population-based investigation from the Melbourne Colorectal Cancer Study.  Dis Colon Rectum. 1990;  33 938-945
• 71 Lang H, Radtke A, Hindennach M et al. Impact of virtual tumor resection and computer-assisted risk analysis on operation planning and intraoperative strategy in major hepatic resection.  Arch Surg. 2005;  140 629-638
• 72 Langenhoff B S, Krabbe P FM, Ruers T JM. Computer-based decision making in medicine: A model for surgery of colorectal liver metastases.  Eur J Surg Oncol. 2007;  33 S 111-S 117
• 73 Leen E, Ceccotti P, Mong S J et al. Potential value of contrast-enhanced intraoperative ultrasonography during partial hepatectomy for metastases. An essential investigation before resection?.  Ann Surg. 2006;  243 236-240
• 74 Leporrier J, Maurel J, Chiche L et al. A population-based study of the incidence, management and prognosis of hepatic metastases from colorectal cancer.  Br J Surg. 2006;  93 465-474
• 75 Lesurtel M, Selzner M, Petrowsky H et al. How should transection of the liver be performed? A prospective randomized study in 100 consecutive patients: comparing four different transection strategies.  Ann Surg. 2005;  242 814-823
• 76 Liang P, Dong B, Yu X et al. Prognostic factors for percutaneous microwave coagulation therapy of hepatic metastases.  AJR. 2003;  181 1319-1325
• 77 Liersch T, Meller J, Bittrich M et al. Update of carcinoembryonic antigen radioimmunotherapy with (¹³¹)I-labetuzumab after salvage resection of colorectal liver metastases: comparison of outcome to a contemporaneous control group.  Ann Surg Oncol. 2007;  14 2577-2590
• 78 Lorenz M, Müller H -H, Schramm H et al. Randomized trial of surgery versus surgery followed by adjuvant hepatic arterial infusion with 5-fluorouracil and folinic acid for liver metastases of colorectal cancer. German Cooperative on Liver Metastases.  Ann Surg. 1998;  228 756-762
• 79 Lyass S, Zamir G, Matot I et al. Combined colon and hepatic resection for synchronous colorectal liver metastases.  J Surg Oncol. 2001;  78 17-21
• 80 Malik H Z, Prasad K R, Halazun K J et al. Preoperative prognostic score for predicting survival after hepatic resection for colorectal liver metastases.  Ann Surg. 2007;  246 806-814
• 81 Manfredi S, Lepage C, Hatem C et al. Epidemiology and management of liver metastases from colorectal cancer.  Ann Surg. 2006;  244 254-259
• 82 Mantke R, Niepmann D, Gastinger I et al. Kurative und diagnostische Resektionen an der Leber. Datenanalyse des Tumorzentrums Brandenburg unter besonderer Berücksichtigung der Tumorentität kolorektales Karzinom.  Chirurg. 2006;  77 1135-1143
• 83 Martin R, Paty P, Fong Y et al. Simultaneous liver and colorectal resections are safe for synchronous colorectal liver metastasis.  J Am Coll Surg. 2003;  197 233-242
• 84 Masi G, Cupini S, Marcucci L et al. Treatment with 5-fluorouracil / folinic acid, oxaliplatin, and irinotecan enables surgical resection of metastases in patients with initially unresectable metastatic colorectal cancer.  Ann Surg Oncol. 2006;  13 58-65
• 85 Mentha G, Majno P E, Andres A et al. Neoadjuvant chemotherapy and resection of advanced synchronous liver metastases before treatment of the colorectal primary.  Br J Surg. 2006;  93 872-878
• 86 Mentha G, Majno P, Terraz S et al. Treatment strategies for the management of advanced colorectal liver metastases detected synchronously with the primary tumour.  Eur J Surg Oncol. 2007;  33: Suppl S 76-S 83
• 87 Miller G, Biernacki P, Kemeny N E et al. Outcomes after resection of synchronous or metachronous hepatic and pulmonary colorectal metastases.  J Am Coll Surg. 2007;  205 231-238
• 88 Minagawa M, Makuuchi M, Torzilli G et al. Extension of the frontiers of surgical indications in the treatment of liver metastases from colorectal cancer: long-term results.  Ann Surg. 2000;  231 487-499
• 89 Minagawa M, Yamamoto J, Miwa S et al. Selection criteria for simultaneous resection in patients with synchronous liver metastasis.  Arch Surg. 2006;  141 1006-1012
• 90 Morise Z, Sugioka A, Fujita J et al. Does repeated surgery improve the prognosis of colorectal liver metastases?.  J Gastrointest Surg. 2006;  10 6-11
• 91 Mulier S, Ni Y, Jamart J et al. Local recurrence after hepatic radiofrequency coagulation. Multivariate meta-analysis and review of contributing factors.  Ann Surg. 2005;  242 158-171
• 92 Mulier S, Ni Y, Jamart J et al. Radiofrequency ablation versus resection for resectable colorectal liver metastases: time for a randomized trial?.  Ann Surg Oncol. 2008;  15 144-157
• 93 Muratore A, Polastri R, Bouzari R et al. Repeat hepatectomy for colorectal liver metastases: A worthwile operation?.  J Surg Oncol. 2001;  76 127-132
• 94 Nagakura S, Shirai Y, Suda T et al. Multiple repeat resections of intra- and extrahepatic recurrences in patients undergoing initial hepatectomy for colorectal carcinoma metastases.  World J Surg. 2002;  26 141-147
• 95 Neeleman N, Andersson R. Repeated liver resection for recurrent liver cancer.  Br J Surg. 1996;  83 893-901
• 96 Nishio H, Hamady Z ZR, Malik H Z et al. Outcome following repeat liver resection for colorectal liver metastases.  Eur J Surg Oncol. 2007;  33 729-734
• 97 Nordlinger B, Jaeck D, Guignet M et al. Résection chirurgicale des Métastases Hépatiques, Enquéte de l'Association Francaise de Chirurgie. Springer, Paris 1992; 141-175. Zitiert bei Elias et al. 2003
• 98 Nordlinger B, Guiguet M, Vaillant M J-C Association Francaise de Chirurgie et al.,. Surgical resection of colorectal carcinoma metastases to the liver. A prognostic scoring system to improve case selection, based on 1568 patients.  Cancer. 1996;  77 1254-1262
• 99 Nordlinger B, Sorbye H, Glimelius B for the EORTC Gastro-Intestinal Tract Cancer Group, Cancer Research UK, Arbeitsgruppe Lebermetastasen und -tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie (ALM-CAO), Australasian Gastro-Intestinal Trials Group (AGITG), and Fédération Francophone de Cancérologie Digestive (FFCD) 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 1007-1016
• 100 Parks R, Gonen M, Kemeny N et al. Adjuvant chemotherapy improves survival after resection of hepatic colorectal metastases: analysis of data from two continents.  J Am Coll Surg. 2007;  204 753-763
• 101 Pawlik T M, Scoggins C R, Zorzi D et al. Effect of surgical margin status on survival and site of recurrence after hepatic resection for colorectal metastases.  Ann Surg. 2005;  241 715-724
• 102 Petrowsky H, Gonen M, Jarnagin W et al. Second liver resections are safe and effective treatment for recurrent hepatic metastases from colorectal cancer: a bi-institutional analysis.  Ann Surg. 2002;  235 863-871
• 103 Petrowsky H, McCormack L, Trujillo M et al. A prospective, randomized, controlled trial comparing intermittent portal triad clamping versus ischemic preconditioning with continuous clamping for major liver resection.  Ann Surg. 2006;  244 921-930
• 104 Portier G, Elias D, Bouche O et al. Multicenter randomized trial of adjuvant fluorouracil and folinic acid compared with surgery alone after resection of colorectal liver metastases: FFCD ACHBTH AURC 9002 trial.  J Clin Oncol. 2006;  24 4976-4982
• 105 Poston G J. Radiofrequency ablation of colorectal liver metastases: Where are we really going?.  J Clin Oncol. 2005;  23 1342-1344
• 106 Poston G J, Adam R, Alberts S et al. OncoSurge: a strategy for improving resectability with curative intent in metastatic colorectal cancer.  J Clin Oncol. 2005;  23 7125-7134
• 107 Pozzo C, Basso M, Cassano A et al. Neoadjuvant treatment of unresectable liver disease with irinotecan and 5-fluorouracil plus folinic acid in colorectal cancer patients.  Ann Oncol. 2004;  15 933-939
• 108 Rau H G, Schauer R, Pickelmann S et al. Dissektionstechniken in der Leberchirurgie.  Chirurg. 2001;  72 105-112
• 109 Rau H G, Wichmann M W, Schinkel S et al. Wasserstrahldissektion bei Leberresektion: Ultraschallaspirator versus Jet-Cutter.  Zentralbl Chir. 2001;  126 586-590
• 110 Reddy S K, Pawlik T M, Zorzi D et al. Simultaneous resections of colorectal cancer and synchronous liver metastases: a multi-institutional analysis.  Ann Surg Oncol. 2007;  14 3481-3491
• 111 Ricke J, Wust P, Wieners G et al. Liver malignancies: CT-guided interstitial brachytherapy in patients with unfavorable lesions for thermal ablation.  J Vasc Interv Radiol. 2004;  15 1279-1286
• 112 Ricke J, Wust P, Stohlmann A et al. CT-guided interstitial brachytherapy of liver malignancies alone or in combination with thermal ablation: phase I-II results of a novel technique.  Int J Radiat Oncol Biol Phys. 2004;  58 1496-1505
• 113 Rosenberg R, Stangl M, Siewert J R. Chirurgische Therapie von Lebermetastasen. In: Siewert JR (Hrsg). Onkologische Chirurgie. 2. Aufl. Springer Medizin, Heidelberg 2006; 575-586
• 114 Rubbia-Brandt L, Giostra E, Brezault C et al. Importance of histological tumor response assessment in predicting the outcome in patients with colorectal liver metastases treated with neo-adjuvant chemotherapy followed by liver surgery.  Ann Oncol. 2007;  18 299-304
• 115 Sahani D V, Kalva S P, Tanabe K K et al. Intraoperative US in patients undergoing surgery for liver neoplasms: comparison with MR imaging.  Radiology. 2004;  232 810-814
• 116 Scheele J, Altendorf-Hofmann A, Grube T et al. Resektion colorectaler Lebermetastasen. Welche Prognosefaktoren bestimmen die Patientenselektion?.  Chirurg. 2001;  72 547-560
• 117 Schefter T E, Kavanagh B D, Timmerman R D et al. A phase I trial of stereotactic body radiation therapy (SBRT) for liver metastases.  Int J Radiat Oncol Biol Phys. 2005;  62 1371-1378
• 118 Schmiegel W, Reinacher-Schick A, Arnold D et al. S 3-Leitlinie „Kolorektales Karzinom” - Aktualisierung 2008. Ergebnis einer evidenzbasierten Konsensuskonferenz. (Manuskript in Vorbereitung)
• 119 Schneider P D. Preoperative assessment of liver function.  Surg Clin N Am. 2004;  84 355-373
• 120 Schüssler-Fiorenza C M, Mahvi D M, Niederhuber J et al. Clinical risk score correlates with yield of PET scan in patients with colorectal hepatic metastases.  J Gastrointest Surg. 2004;  8 150-155
• 121 Selzner M, Hany T F, Wildbrett P et al. Does the novel PET / CT imaging modality impact on the treatment of patients with metastatic colorectal cancer of the liver?.  Ann Surg. 2004;  240 1027-1036
• 122 Shaw I M, Rees M, Welsh F KS et al. Repeat hepatic resection for recurrent colorectal liver metastases is associated with favourable long-term survival.  Br J Surg. 2006;  93 457-464
• 123 Shimada H, Tanaka K, Masui H et al. Results of surgical treatment for multiple (> 5 nodules) bi-lobar hepatic metastases from colorectal cancer.  Langenbecks Arch Surg. 2004;  389 114-121
• 124 Simillis C, Constantinides V A, Tekkis P P et al. Laparoscopic versus open hepatic resections for benign and malignant neoplasms - a meta-analysis.  Surgery. 2007;  141 203-211
• 125 Siperstein A E, Berber E, Ballem N et al. Survival after radiofrequency ablation of colorectal liver metastases. 10-year experience.  Ann Surg. 2007;  246 559-567
• 126 Sjövall A, Järv V, Blomqvist L et al. The potential for improved outcome in patients with hepatic metastases from colon cancer: a population-based study.  Eur J Surg Oncol. 2004;  30 834-841
• 127 Sommer G, Schaefer O, Ludwig U et al. Sliding multislice MRI for abdominal staging of patients with pelvic malignancies. A pilot study.  J Magn Reson Imaging. 2008;  ,  (ahead of print)
• 128 Souglakos J, Androulakis N, Syrigos K et al. FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) vs FOLFIRI (folinic acid, 5-fluorouracil and irinotecan) as first-line treatment in metastatic colorectal cancer (MCC): a multicentre randomised phase III trial from the Hellenic Oncology Research Group (HORG).  Br J Cancer. 2006;  94 798-805
• 129 Sugarbaker P H. Repeat hepatectomy for colorectal metastases.  J Hepatobiliary Pancreat Surg. 1999;  1 30-38
• 130 Sugawara G, Isogai M, Kaneoka Y et al. Repeat hepatectomy for recurrent colorectal metastases.  Surg Today. 2005;  35 282-289
• 131 Suzuki S, Sakaguchi T, Yokoi Y et al. Impact of repeat hepatectomy on recurrent colorectal liver metastases.  Surgery. 2001;  129 421-428
• 132 Takahashi S, Inoue K, Konishi M et al. Prognostic factors for poor survival after repeat hepatectomy in patients with colorectal liver metastases.  Surgery. 2003;  133 627-634
• 133 Tanaka K, Shimada H, Ohta M et al. Procedures of choice for resection of primary and recurrent liver metastases from colorectal cancer.  World J Surg. 2004;  28 482-487
• 134 Tannapfel A, Reinacher-Schick A. Chemotherapie-assoziierte Hepatotoxizität in der Behandlung des kolorektalen Karzinoms.  Zeitschr Gastroenterol. 2008;  46 435-440
• 135 Thelen A, Jonas S, Benckert C et al. Simultaneous versus staged liver resection of synchronous liver metastases from colorectal cancer.  Int J Colorect Dis. 2007;  22 1269-1276
• 136 Tuttle T M, Curley S A, Roh M S. Repeat hepatic resection as effective treatment of recurrent colorectal liver metastases.  Ann Surg Oncol. 1997;  4 125-130
• 137 UICC .TNM Supplement 2^nd ed. Wittekind C, Henson DE, Hutter RVP, Sobin LH (eds). A commentary on uniform use. John Wiley & Sons, New York 2001
• 138 UICC .TNM Supplement 3^rd ed. Wittekind C, Henson DE, Hutter RVP, Sobin LH (eds). A commentary on uniform use. John Wiley & Sons, New York 2003
• 139 Vauthey J -N, Choti M A, Helton W S. AHPA / SSO / SSAT Consensus conference on hepatic colorectal metastases: Rationale and overview of the conference.  Ann Surg Oncol. 2006;  13 1259-1260
• 140 Vogl T J, Mack M G, Balzer J O et al. Liver metastases: neoadjuvant downsizing with transarterial chemoembolization before laser-induced thermotherapy.  Radiology. 2003;  229 457-464
• 141 Vogl T J, Straub R, Eichler K et al. Colorectal carcinoma metastases in liver: laser-induced interstitial thermotherapy - local tumor control rate and survival data.  Radiology. 2004;  230 450-458
• 142 Yamamoto J, Kosuge T, Shimada K et al. Repeat liver resection for recurrent colorectal liver metastases.  Am J Surg. 1999;  178 275-281
• 143 Zelek L, Bugat R, Cherqui D on behalf of the European Association for Research in Oncology, Créteil, France et al. Multimodal therapy with intravenous biweekly leucovorin, 5-fluorouracil and irinotecan combined with hepatic arterial infusion pirarubicin in non-resectable hepatic metastases from colorectal cancer (a European Association for Research in Oncology trial).  Ann Oncol. 2003;  14 1537-1542
• 144 Zorzi D, Mullen J T, Abdalla E K et al. Comparison between hepatic wedge resection and anatomic resection for colorectal liver metastases.  J Gastrointest Surg. 2006;  10 86-94
• 145 Zorzi D, Laurent A, Pawlik T M et al. Chemotherapy-associated hepatotoxicity and surgery for colorectal liver metastases.  Br J Surg. 2007;  94 274-286