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Print version ISSN 0102-6720
ABCD, arq. bras. cir. dig. vol.24 no.4 São Paulo Oct./Dec. 2011
Marcos Vinicius Perini; Fabricio Ferreira Coelho; Fabio Ferrari Makdissi; Renato Miccelli Lupinacci; Marcel Autran Machado; Paulo Herman
INTRODUCTION: Nowadays, liver resections
can be performed with acceptable morbi-mortality rates. In specialized centers,
mortality as low as 1% can be achieved, even with the advent of new hepatotoxic
chemotherapy regimens. In order to reduce morbidity and mortality, newer strategies
can be undertaken, such as portal vein embolization, radiofrequency ablation
techniques, re-hepatectomies, major vascular resections and two stages hepatectomies.
METHOD: Literature review was conducted on sites search PubMed, BIREME, SciELO, with the headings "partial hepatectomy, hepatic metastases, colorectal cancer, radiofrequency and embolization". Were selected mainly studies with the application of techniques and surgical procedures in the treatment of liver metastasis.
CONCLUSION: Survival rates as good as 50% in 5y can be achieved in selected cases when a multidisciplinary team is involved. Better surgical techniques, with parenchimal sparing strategies and the advent of neoadjuvant chemotherapy can turn unresectable liver lesions to resectable and increase survival rates.
Headings: Partial hepatectomy. Hepatic metastases. Colorectal cancer. Radiofrequency. Embolization.
A few years ago, only 15 to 20% of patients with liver metastases of colorectal cancer were considered candidates for surgical treatment with curative intent. With the strategies discussed here involving the performance of a multidisciplinary team including a surgeon, oncologist, radiologist and interventional radiologist, currently the resection of hepatic metastases from colorectal tumors can be accomplished in 30% to 40% of patients.
Is considered resectable the liver metastases that are capable of being removed with free margin and when around 25% to 30% of functional liver mass is preserved.
In 2006, the Consensus of Resectability IHBPA defined as: 1) ability to preserve two contiguous liver segments with adequate preservation of the influx, efflux and biliary drainage of the remnant liver parenchyma and 2) remnant liver greater than 20% without disease (liver disease) . It is recommended safety margins greater than 1 cm but these are not mandatory and the presence of resectable extrahepatic disease is not a contraindication to liver resection1,9,11.
In everyday practice, we can divide the patients suffering from the disease in easily resectable, marginally resectable and unresectable. Obviously special attention must be focused on the last two groups, since the technical feasibility of hepatectomy becomes defiant and preoperative clinical approach demand integration among different professionals (radiologists, surgeons and oncologists). The main causes of non-resectability are the presence of multiple nodules in both hepatic lobes, involvement of the hepatic pedicle and the hepatic veins and the presence of extrahepatic disease.
In the present article will be reviewed the main strategies used in marginally resectable patients that aim to make them resectable. Among these different tactics, exist the portal embolization, radiofrequency, liver resection in two stages, the re-hepatectomy and extreme liver resections.
There is no doubt that chemotherapy is part of strategies to increase resectability, decreasing the size of the nodules and also helping to increase survival in patients undergoing resection of metastases. Neoadjuvant chemotherapy has been used routinely in patients with liver metastases of colorectal tumors with the aim of eradicating not visible disease, to test the biological sensitivity of the tumor and chemotherapy to become resectable in patients considered unresectable15.
Selective portal embolization
Aims to lead to hypertrophy of the remnant liver to prevent postoperative liver failure. This is more common in patients who were previously treated with chemotherapy which can cause hepatotoxicity (liver where the regenerative capacity is impaired) and require resection involving more than 60% to 70% of the hepatic parenchyma. The hepatocellular damage caused by chemotherapy depends on the agent used. It is known that irinotecan leads to steatohepatitis and this condition increases the mortality of liver resections, whereas oxaliplatin leads to sinusoidal dilatation, increasing the risk of intraoperative bleeding, but with no impact on mortality20,23.
Typically, in healthy livers, resection of 70% to 80% of the liver do not progress to liver failure. However, in the presence of prior liver injury (chemotherapy, steatosis or cirrhosis) resection of more than 60% of the liver can lead to a condition of postoperative liver failure. Therefore, when treating liver undergoing chemotherapy, for more than 3 to 4 months, remaining liver (measured by liver volumetry using computed tomography) less than 40% it is recommended portal embolization. This should also be recommended in patients with metabolic diseases (obesity) where hepatic steatosis is frequent.
Hepatic measuring does not mean measurement of liver function; however the studies take into account in the West are focused more in mass size than functional aspects. In the East, the function measurement can be accomplished by determining the clearance of indocyanine green (drug completely metabolized in the liver). In the West, studies take into account the existence of tissue damage (revealed by biopsy, imaging, or by changes in the use of hepatotoxic drugs). Liver volume is measured by the total surface of corporal area - ASC (total liver volume = -794.41 + 1268.28 x BSA). The remnant liver volume - VFR - can be measured using the formula = VFR measured/VFR. VFR is greater than 30% in patients undergoing multiple cycles of chemotherapy with the aim of reducing the incidence of postoperative liver failure14.
Although some authors argue that the ligation of the portal vein (branch of the side to be resected, usually the right) is as effective as embolization done by interventional radiology (through the use of springs, microparticles, cyanoacrylate), most of the services of liver surgery prefer transparietal puncture embolization6,24.
After four to six weeks of embolization or ligation of the portal vein occurs hemi-compensatory hypertrophy of the remnant liver and resection can be done successfully (the largest increase in liver volume occurs at the end of the third week, where it can be seen 75% growth). During this period, chemotherapy can be performed without damage to regeneration and ablation techniques. Patients who experience tumor growth or appearance of new lesions or poor hepatic hyperplasia are usually not considered candidates to resection7 (Figure 1).
Methods of tumor ablation
Among these, there is the radiofrequency (RF) as the most widely used method16. Although not considered curative method its use in colorectal metastases has been increasing referred for both situations: disease control and helping the curative treatment (resection). Lesions up to 3 cm can be treated by RF, both percutaneously or surgically (laparoscopy or laparotomy). Usually patients are treated with RF when damage does not spread outside the liver or when there it is possibility to control (or can control) the extrahepatic disease2,17. Most centers consider the patient treatable with up to four liver lesions. Lesions located on the periphery of the liver may eventually be treated by RF, although the chance of complications such as rupture, biliary fistula and bleeding are higher. However, if these lesions are in contact with abdominal hollow viscera, the risk of perforation contraindicate the procedure. The treatment of tumors adjacent to the gallbladder and the hepatic hilum may lead to thermal injury and risk of biliary fistula or biliary stricture.
The best indications are absence of clinical conditions for liver resection and in those with bilateral disease where there is need to perform a partial hepatectomy in one lobe and ablation of nodules in the remnant liver. Lesions in contact with or very near vascular vessels can be treated with some degree of effectiveness when employing certain maneuvers, such as hilar vascular occlusion, reducing the inflow of blood and thus reducing heat loss25(Figure 2).
It should be considered in the presence of bilateral liver disease, where resection of more than 70% of the liver should be performed in two-stage hepatectomy. In this situation, resection of the nodules on one side of the liver should be done in the first place followed or not by portal ligation/embolization (in the same surgery or postoperatively). In a second stage, resection of the previously embolized hemi-liver can be done safely. The purpose of this second strategy is to make safe and potentially curative operation, leaving sufficient functional parenchyma avoiding liver failure3,22. In the interval between two operations (or soon after portal embolization) chemotherapy can be administered two to three weeks after the procedure, aiming to prevent tumor growth. When there is disease progression during this period, these individuals are not usually considered candidates for the second procedure, and this number could reach 20%. Survival at three years can reach 54% of the costs of morbidity in 30% after the first procedure and 45% after the second13,22.
After liver resection with curative intent, approximately 60% to 70% of patients will experience disease recurrence, and of this amount, one third will relapse only in liver. Of this group, about 10% to 30% will present new conditions for liver resection, being candidates for re-hepatectomy. Despite the technical difficulties of the procedure, some studies have shown complications and survival rates similar to first resection5,21. In bi-institutional study, median survival of 37 months was achieved. Patients with interval between resections greater than one year have a more favorable prognosis18. There are few series in which one or more third hepatectomies were necessary, however good results can be achieved selected cases4.
Extreme hepatic resections
When there are metastatic lesions involving the confluence of the hepatic veins or invading the superior vena cava, resections are generally not feasible due to risk of intraoperative bleeding and gas embolism. However in some cases, total vascular exclusion can be performed with or without resection and reconstruction of the inferior vena cava with possible prosthesis to replace it. Usually, these situations need to clamping of the inflow (portal and arterial) associated with the control of the vena cava, infra and supra hepatic. When these maneuvers, usually occurs hemodynamic instability and, eventually, the use of venovenous bypass may be necessary. Modifications of this technique can be used as the preservation of caval flow by clamping of the hepatic veins10. In this condition, there is less hemodynamic changes and resections can be performed more safely.
The normothermic liver ischemia with clamping of the hepatic pedicle and the inferior vena cava above and below the liver can be tolerated for up to 60 minutes making safer resection of these tumors12. Some authors advocate the use of cold ischemia (hypothermic) with the same clamping associated with liver perfusion with cold preservation solution (used in transplants) in order to reduce the harm to the liver parenchyma during resection complex, which would lead to lower morbidity post surgery and a lower incidence of renal failure. In these extreme situations the rate of operative mortality in expert hands is 5% to 10%, morbidity 64% and five-year survival of 38%8. It should be noted that only is multidisciplinary follow-up and periodic re-evaluations together with the team can lead to better treatment of this group of patients.
The various strategies used in patients with liver metastases, initially unresectable seem to aim at curative resection, leaving 30% to 40% of functional liver parenchyma. Treatment should be individualized and the involvement of professionals from various areas of medicine should be encouraged. The initial chemotherapy (neoadjuvant) is essential in treating these patients, and after initial chemotherapy and lesions response (decreased or remained stable), some strategies can be employed, namely: 1) whether the unilateral resection of the lesions will leave liver remnant of less than 30%, hold portal embolization; 2) if three to five lesions up to 3 cm in diameter will remain after hepatic resection containing the greatest amount of metastatic liver disease, it can be associated to it ablative techniques (radiofrequency) or enucleation; 3) if more than five lesions or single lesion greater than 3 cm will be left in the remnant liver, perform hepatectomy in two stages usually associated with selective embolization or ligation of the portal vein.
1. Abdalla EK, Adam R, Bilchik AJ, Jaeck D, Vauthey JN, Mahvi D. Improving resectability of hepatic colorectal metastases: expert consensus statement. Ann Surg Oncol, 2006. 13(10): p. 1271-80. [ Links ]
2. Abdalla EK, Vauthey JN, Ellis LM, Ellis V, Pollock R, Broglio KR, Hess K, Curley SA. Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases. Ann Surg, 2004. 239(6):818-25. [ Links ]
3. Adam R, Laurent A, Azoulay D, Castaing D, Bismuth H. Two-stage hepatectomy: A planned strategy to treat irresectable liver tumors. Ann Surg, 2000. 232(6): 777-85. [ Links ]
4. Adam R, Pascal G, Azoulay D, Tanaka K, Castaing D, Bismuth H. Liver resection for colorectal metastases: the third hepatectomy. Ann Surg, 2003. 238(6): 871-83. [ Links ]
5. Antoniou A, Lovegrove RE, Tilney HS, Heriot AG, John TG, Rees M, Tekkis PP, Welsh FK. Meta-analysis of clinical outcome after first and second liver resection for colorectal metastases. Surgery, 2007. 141(1): 9-18. [ Links ]
6. Aussilhou B, Lesurtel M, Sauvanet A, Farges O, Dokmak S, Goasguen N, Sibert A, Vilgrain V, Belghiti J. Right portal vein ligation is as efficient as portal vein embolization to induce hypertrophy of the left liver remnant. J Gastrointest Surg, 2008. 12(2): 297-303. [ Links ]
7. Azoulay D, Castaing D, Smail A, Adam R, Cailliez V, Laurent A, Lemoine A, Bismuth H. Resection of nonresectable liver metastases from colorectal cancer after percutaneous portal vein embolization. Ann Surg, 2000. 231(4): 480-6. [ Links ]
8. Azoulay D, Eshkenazy R, Andreani P, Castaing D, Adam R, Ichai P, Naili S, Vinet E, Saliba F, Lemoine A, Gillon MC, Bismuth H. In situ hypothermic perfusion of the liver versus standard total vascular exclusion for complex liver resection. Ann Surg, 2005. 241(2):277-85. [ Links ]
9. Charnsangavej C, Clary B, Fong Y, Grothey A, Pawlik TM, Choti MA. Selection of patients for resection of hepatic colorectal metastases: expert consensus statement. Ann Surg Oncol, 2006. 13(10): 1261-8. [ Links ]
10. Cherqui D, Malassagne B, Colau PI, Brunetti F, Rotman N, Fagniez PL. Hepatic vascular exclusion with preservation of the caval flow for liver resections. Ann Surg, 1999. 230(1): 24-30. [ Links ]
11. Costa SRP, Araujo SLM, Teixeira OA, Pereira AC. Setorectomia posterior direita laparoscópica no tratamento dos tumores hepáticos. ABCD Arq Bras Cir Dig 2010;23(4):275-279 [ Links ]
12. Huguet C, Gavelli A, Chieco PA, Bona S, Harb J, Joseph JM, Jobard J, Gramaglia M, Lasserre M. Liver ischemia for hepatic resection: where is the limit? Surgery, 1992. 111(3): 251-9. [ Links ]
13. Jaeck D, Oussoultzoglou E, Rosso E, Greget M, Weber JC, Bachellier P. 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(6): 1037-49. [ Links ]
14. Kishi Y, Abdalla EK, Chun YS, Zorzi D, Madoff DC, Wallace MJ, Curley SA, Vauthey JN. Three hundred and one consecutive extended right hepatectomies: evaluation of outcome based on systematic liver volumetry. Ann Surg. 2009 Oct;250(4):540-8. [ Links ]
15. Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, Bechstein WO, Primrose JN, Walpole ET, Finch-Jones M, Jaeck D, Mirza D, Parks RW, Collette L, Praet M, Bethe U, Van Cutsem E, Scheithauer W, Gruenberger T. 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 Mar 22;371(9617):1007-16. [ Links ]
16. O'Rourke AP, Haemmerich D, Prakash P, Converse MC, Mahvi DM, Webster JG. Current status of liver tumor ablation devices. Expert Rev Med Devices, 2007. 4(4): p. 523-37. [ Links ]
17. Patterson, E.J., et al., Radiofrequency ablation of porcine liver in vivo: effects of blood flow and treatment time on lesion size. Ann Surg, 1998. 227(4): p. 559-65. [ Links ]
18. Petrowsky H, Gonen M, Jarnagin W, Lorenz M, DeMatteo R, Heinrich S, Encke A, Blumgart L, Fong Y. Second liver resections are safe and effective treatment for recurrent hepatic metastases from colorectal cancer: a bi-institutional analysis. Ann Surg. 2002 Jun;235(6):863-71. [ Links ]
19. Ribero D, Abdalla EK, Madoff DC, Donadon M, Loyer EM, Vauthey JN. Portal vein embolization before major hepatectomy and its effects on regeneration, resectability and outcome. Br J Surg. 2007 Nov;94(11):1386-94. [ Links ]
20. Rubbia-Brandt L, Audard V, Sartoretti P, Roth AD, Brezault C, Le Charpentier M, Dousset B, Morel P, Soubrane O, Chaussade S, Mentha G, Terris B. Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Ann Oncol. 2004 Mar;15(3):460-6. [ Links ]
21. Suzuki S, Sakaguchi T, Yokoi Y, Kurachi K, Okamoto K, Okumura T, Tsuchiya Y, Nakamura T, Konno H, Baba S, Nakamura S. Impact of repeat hepatectomy on recurrent colorectal liver metastases. Surgery. 2001 Apr;129(4):421-8. [ Links ]
22. Togo S, Nagano Y, Masui H, Tanaka K, Miura Y, Morioka D, Endo I, Sekido H, Ike H, Shimada H. Two-stage hepatectomy for multiple bilobular liver metastases from colorectal cancer. Hepatogastroenterology. 2005 May-Jun;52(63):913-9. [ Links ]
23. Vauthey JN, Pawlik TM, Ribero D, Wu TT, Zorzi D, Hoff PM, Xiong HQ, Eng C, Lauwers GY, Mino-Kenudson M, Risio M, Muratore A, Capussotti L, Curley SA, Abdalla EK. Chemotherapy regimen predicts steatohepatitis and an increase in 90-day mortality after surgery for hepatic colorectal metastases. J Clin Oncol. 2006 May 1;24(13):2065-72. [ Links ]
24. Wilms C, Mueller L, Lenk C, Wittkugel O, Helmke K, Krupski-Berdien G, Rogiers X, Broering DC. Comparative study of portal vein embolization versus portal vein ligation for induction of hypertrophy of the future liver remnant using a mini-pig model. Ann Surg. 2008 May;247(5):825-34. [ Links ]
25. Wong SL, Mangu PB, Choti MA, Crocenzi TS, Dodd GD 3rd, Dorfman GS, Eng C, Fong Y, Giusti AF, Lu D, Marsland TA, Michelson R, Poston GJ, Schrag D, Seidenfeld J, Benson AB 3rd. American Society of Clinical Oncology 2009 clinical evidence review on radiofrequency ablation of hepatic metastases from colorectal cancer. J Clin Oncol. 2010 Jan 20;28(3):493-508. [ Links ]
Correspondence: Financial source: none Received for publication: 16/01/2011 From the Department of Surgery of the Liver and
Portal Hypertension, Department of Gastroenterology, Hospital das Clínicas,
Faculty of Medicine, University of São Paulo, São Paulo, SP, Brazil.
Conflicts of interest: none
Accepted for publication: 20/04/2011
Financial source: none
Received for publication: 16/01/2011
From the Department of Surgery of the Liver and Portal Hypertension, Department of Gastroenterology, Hospital das Clínicas, Faculty of Medicine, University of São Paulo, São Paulo, SP, Brazil.