Surgical management of hepatic metastases from colorectal cancer

1. Surgical management of hepatic metastases from colorectal cancer Joint Hospital Surgical Grand Round Dr HH Wong Department of Surgery PYNEH

4. Liver is the commonest site of distant metastasis of colorectal cancer • Nearly half of the patients with colorectal cancer ultimately develop liver metastasis during the course of their diseases • Liver metastasis may be present in as many as 35% of patients with colorectal cancer at the time of operation

5. Prognosis of patients with untreated liver metastasis • extent of hepatic involvement at the time of diagnosis • Histological grade of the primary tumour

6. 0 % five-year survival for patients with untreated but potentially resectable liver metastases • 28 % five-year survival for operated patients with resected liver metastases - Wilson SM, Adson MA. Surgical treatment of hepatic metastases from colorectal cancer. Arch Surg 1976; 111: 330-334 )

7. patients with an untreated single liver metastasis had a median survival of 19 months, with no patients surviving 5 years • while patients with a resected single liver metastasis had a median survival of 36 months with 25 % of patients surviving five years • Wanebo HJ, Semoglou C, Attiyeh F, Stearns MJ Jr. Surgical management of patients with primary operable colorectal cancer and synchronous liver metastases. Am J Surg 1978; 135: 81-85

8. Surgical resection of distant metastases in colorectal cancer can produce long-term survival and cure in some selected patients. • Five-year survival rates after resection of all detectable liver metastases range from 6 to 52 %

9. Traditional selection criterion • No more than 3 metastases • Unilobar disease • Tumours < 5cm • Metachronous detection of metastases • Resection margin > 1cm required • No extrahepatic disease • Not > 65 of age • No portal nodal involvement

10. Unilobar or bilobar disease • Only 1/3 of patients with colorectal liver metastases have disease limited to one lobe • segment-based resection allows excision of bilateral or multiple liver lesions that might previously have been deemed unresectable

11. Unilobar or bilobar disease • Up to 75 % of the liver can be removed if the liver function is normal • Vauthey JN. Liver imaging. A surgeon's perspective. Radiol Clin North Am 1998;36(2):445-57

12. Number of metastases • Long-term survival is rare in patient with resection of four or more lesions • Ekberg H. determinants of survival in liver resection for colorectal secondaries. Br J Surg 1986; 73: 727-31 • patients who underwent resection of more than four colorectal liver metastases revealed an overall 5 year survival rate of 23% • Weber SM et al. Survival after resection of multiple hepatic colorectal metastases. Ann Surg Oncol 7: 643-650, 2000

13. Number of metastases • no significant difference in the mortality, morbidity and five-year survival between patients whose lesions more than four and those less than four • Morris DL. Surgery for liver metastases: How many? ANZ J Surg 2002; 72: 2 • Minagawa M et al. Extension of the frontiers of surgical indications in the treatment of liver metastases from colorectal cancer: Longterm results. Ann Surg 231: 487-499, 2000

14. Resection margin • Patients with incomplete removal of tumour have similar outcomes to non-operated patients • Scheele J et al. Hepatic metastases from colorectal carcinoma: impact of surgical resection on the natural history. Br J Surg, 77, 1241-6

15. Resection margin • Registry of Hepatic Metastases • Margin greater than 1cm was associated with a 45% 5-year survival • Only 23% survived 5 years if the margin was less

16. Resection margin • Recent reports suggest a generous margin is not essential for achieving a curative outcome • Yamamoto J et al. Factors influencing survival of patients undergoing hepatectomy for colorectal metastases. Br J Surg, 86, 332-7 • Minagawa M et al. extension of the frontiers of surgical indications in the treatment of liver metastases from colorectal cancer. Ann Surg, 231, 487-99

17. Resection margin • 1mm tumour –free resection margin is enough to achieve comparable survival and disease-free survival • Hamady Z et al. Current techniques and results of liver resection for colorectal liver metastasis. Br Med Bull 2004; 70: 87-104

18. Other factors associate with poor prognosis • Metastasis greater than 6cm • Presence of extrahepatic metastases • Portal LN involvement • None of these patients survives 5 years after hepatectomy • Elevated pre-operative CEA level

19. Synchronous colorectal and liver resection • Liver metastasis may be present in as many as 35% of patients with colorectal cancer at the time of operation • Combined single-stage resection of colorectal cancer and liver metastases • Earlier initiation of adjuvant therapy • Avoiding a second laparotomy

20. Synchronous colorectal and liver resection • Safe and feasible with no increase in perioperative morbidity or mortality • No difference in survival compared with staged resection • Lyass S et al. combined colon and hepatic resection for synchronous colorectal liver metastases. J Surg Oncol, 78, 17-21 • Jeack D et al. Strategie Chirurgicale dans le traitement des mestatases hepatiques synchornes des cancers colorectaux. Analyse d’une serie de 59 malades operes. Chirurgie, 124, 258-63

21. R Martin et al. Simultaneous liver and colorectal resections are safe for synchronous colorectal liver metastasis. Journ Am Col Surg 2003; 197: 233-241 240 patients were treated surgically for primary adenocarcinoma of the large bowel and synchronous hepatic metastasis 134 patients underwent simultaneous resection 106 patients underwent staged operations Synchronous colorectal and liver resection

22. Synchronous colorectal and liver resection • Complications were less common in the simultaneous resection group • 65 patients (49%) sustaining 142 complications for simultaneous resection group • 71 patients (67%) sustaining 197 complications for both hospitalizations in the staged resection group (p < 0.003) • Patients having simultaneous resection required fewer days in the hospital (median 10 days versus 18 days, P = 0.001) • Perioperative mortality was similar (simultaneous, N = 3; staged, N = 3).

23. Laparoscopic liver resection • Not widely accepted in view of technical difficulties • Tumour cell seedings at port sites • Overall morbidity has been shown to be lower with laparoscopic resection • Gigot J et al. laparoscopic liver resection for malignant liver tumours. Ann Surg, 236, 90-7

24. Doubling of resection rates • Only 25 % of patients with colorectal liver metastases are candidates for liver resection • Various methods to increase resectability

25. Neoadjuvant chemotherapy • Downstaging of tumour to convert unresectable tumours into potentially resectable ones • Permit resection of about 15% of metastases which have previously been considered unresectable • Adam R et al. Five-year survival following hepatic resection after neoadjuvant therapy for nonresectable colorectal liver metastases. Ann Surg Oncol, 8, 347-53 • It rarely changes the tumour relationship to the vascular structures

26. Preoperative portal vein embolization • Inducing ipsilateral atrophy and contralateral hypertrophy of the liver remnant in these patients • Increase 50% the size of the non-embolized lobe in 4-6 weeks • Abdalla EK, Hicks ME, Vauthey JN. Portal vein embolization: rationale, technique and future prospects. Br J Surg. 2001;88:165–175

27. Preoperative portal vein embolization • Curative liver resection expected to be feasible in ~50% patient who were initially considered inoperable • 5 year suvival apporaching 37% • Elias D et al. Preoeprative selective portal vein embolization before hepatectomy for liver metastases: long term results and impoact on survival. Surgery, 131, 294-9

28. Two-stage resection • Convert non-resectable liver metastases into potentially curable cases • Especially applied to multinodular bilobar metastase • First-stage resection remove the highest possible number of tumour lesions

29. Two-stage resection • Followed by liver regeneration period and chemotherapy • 2nd stage only perfomred if potentially curative and only if enough parenchymal hypertrophy has occurred to reduce the risk of postoperative liver failure. • Adam R, Laurent A, Azoulay D, et al. Two-stage hepatectomy: a planned strategy to treat irresectable liver tumors. Ann Surg. 2000;232:777–785.

30. Only 25 % of patients with colorectal liver metastases are candidates for liver resection • Other treatment modalities, such as local ablative therapy, systemic chemotherapy, hepatic artery infusion and isolated hepatic infusion may offer palliation and prolongation of disease-free and overall survival

31. Local ablative therapy • Radiofrequency ablation • Cryotherapy • Percutaneous ethanol injection • Laser and photodynamic therapy

32. Radiofrequency ablation • An electrode delivers a high-frequency alternating current to the tissue, causing hyperthermia and finally inducing coagulative necrosis • Single rigid probes inducing a cylindrical necrotic lesion • Multi-tined expandable electrodes induce a spherical lesion

33. Radiofrequency ablation • Multiple insertions may be necessary when tumours are >3cm in diameter • Probe placed under ultrasound or CT guidance • RFA can be performed in combination with resection

34. Radiofrequency ablation • High complete response rates of 52%-95% are achieved by RFA • Curley SA et al. radiofrequency ablation of malignant liver tumours. Ann Surg Oncol 2003; 10: 338-237 • Ruers TJ et al. Long –term results of treating hepatic colorectal metastases with cryosurgery. Br J Surg 2001

35. Radiofrequency ablation • Prolongation of disease free and overall survival to repectively 50% and 94% at 1 year • Median survival time of 30-34 months • Solbiati L et al. Radiofrequency thermal ablation of hepatic metastases. Eur J Ultrasound 2001; 13: 149-158

36. Hepatic resection vs. RFA • Aloia, Thomas A et al. Solitary Colorectal Liver Metastasis: Resection Determines Outcome. Arch Surg 141(5), 2006, p 460–467 • 150 underwent HR and 30 underwent RFA • Local recurrence (LR) rate was markedly lower after HR (5%) than after RFA (37%) (P<.001). • Treatment by HR was associated with longer 5-year survival rates than RFA • LR-free (92% vs 60%, respectively; P<.001) • disease-free (50% vs 0%, respectively; P = .001) • overall (71% vs 27%, respectively; P<.001) survival rates

37. Hepatic resection vs. RFA • Tumors 3 cm or larger (n = 79) • LR occurred more frequently following RFA (31%) than after HR (3%) (P = .001) • 5-year LR-free survival rate of 66% after RFA vs 97% after HR (P<.001). • Tumors < 3cm • longer 5-year overall survival rates after HR (72%) as compared with RFA (18%) (P = .006).

38. Conclusion • Hepatic resection remains the only possible cure for colorectal liver metastases • Changing criteria for hepatic resection has doubled the resection rate • Promising treatment modalities to increase resectablitiy • RFA can achieve good results in patient with non-resectable disease, however, itself alone cannot replace hepatic resection in potentially curative cases

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