1. Surgery of colorectal liver metastasis
Juozas Pundzius
Surgery clinic of Kaunas university of medicine

2. Incidence of liver metastasis in colorectal cancer
At the time of diagnosis of primary colorectal cancer:
in 15-20% liver metastases are detectable
In 15% udetectable liver metastases present
(Synchronous disease)
Sasson A.R., Sigurdson E.R. et al; Seminars in Oncology; Vol 29, No 2, 2002
After curative surgery in 20-30% developing subsequent spread to the liver;
(Metachronous disease)
Weinreich D Semin Oncol 29:136:144, 2002
~ 50% of IV stage patients, liver is the only site of metastatic process;
~ 30% of patients with liver metastases are suitable for curative surgery.

3. Methods of treatment of liver metastasis
Curative
Surgical – hepatic resection;
With or without adjuvant therapy;
Palliative
Medical – chemoterapy (systemic or regional);
Surgical;
Ablative techniques:
RFA
Ethanol injections
Cryotherapy;
Vesel ligation, embolization
Chemoembolization
Radiation

4. Curative possibilities of colorectal liver metastases
Hepatic resection is the only form of treatment that offers a long-term survival for patients with liver metastases from colorectal cancer, with 5-year survival ranging from 25% to 39%.
Tanaka K, Shimada H. et al Surgery Vol. 137: , 2005

5. Long term results after CRC liver metastases surgery
Study
Year
No. of patients
5-year survival
(overall)
Median survival
(Mo)
Hughes et al
Scheele et al
Nordlinger et al
Jamison et al
Fong et al
Iwatsuki et al
1986
1995
1996
1997
1999
607
434
1,568
280
1,001
305
33%
28%
27%
37%
32% - 40 33 42

6. Long term results – our data

7. Prognostic factors influencing long term results after curative surgery
Extrahepatic disease;
Primary tumor stage;
Number and size of liver matastases;
Disease free interval;
Margins;
Other ( age, CEA).

8. Prognostic factors for long term results- extrahepatic disease
Mayo Clinic
0% 5 year survival with extrahepatic disease (22 patients);
Memorial Sloan-Kettering Cancer Center
Patients with and without extrahepatic disease 5 year survival 18% vs 38%;(1.001pts)
Fong Y, Fortner J et al Ann Surg 230: , 1999
Elias D, Lasser P, De/Cl/Nouveche, Dec, 1991
Registry of Hepatic Metastases
Metastatic lymphadenopathy (portal and celiac nodes) markedly decreased survival with no 5 year survival reported (850 patients, retrospective study);
Registry of Hepatic Metastases, Surgery, 103: , 1988

9. Restrictions for surgery in case of extrahepatic disease
Liver resection restricted in:
Presence of metastasis in two or more organs - lung, liver, colon (recurence) in case of multiple metastasis in one of them
Carcinomatosis, pleuritis, ascitis
Presence of portal or celiac lymph node metastasis proved by biopsy and extra pathology?

10. Prognostic factors for long term results– primary tumor stage
Patients with lymphatic spread have a decreased survival compared to patients without lymphatic spread, 41% vs 32% ( p = 0.05 analysis of patients);
Fong Y, Fortner J et al Ann Surg 230: , 1999
Stage II primary have an improved outcome compared to patients with stage III primary;
Scheele J., Stangl R. et al; World J Surg, 19:59-71,1995
Nordliger B., Guiget M et al; Cancer 77: ,1996

11. Suggestions for therapy in case of primary tumor spread
Node positive patients – candidates for adjuvant therapy

12. Prognostic factors for long term results– number of liver metastases
Increasing number of metastases – decreasing survival
Experience-
155 patients who had 4 and more lesions:
5 – year survival after 9 to 20 metastases resected - 14%.
increasing number of metastases and positive resection margin - independent prognostic factors (multivariate analysis).
Weber SM, Jarnagin WR et al Ann Surg Oncol7: , 2000
Statement-
increased number of metastasis increasing likelihood of undetectable metastasis

13. Restrictions for surgery in case of multiple liver metastases
1- 3 metastasis in one liver lobe are suitable for curative liver resection
Patients with 4 and more mts in one or both liver lobes are candidates for neoadjuvant treatment
after 2 months chemotherapy in case of no manifestation of new metastasis possibilities of surgery should be discussed

14. Prognostic factors for long term results– disease free interval
Experience-
Difference of median survival in
synchronous vs. metachronous disease
27 months vs. 37 months
Scheele J., Stangl R. et al; World J Surg, 19:59-71,1995
Statements:
Increasing disease-free interval associated with improved survival.
Fong Y, Fortner J et al Ann Surg 230: , 1999
Synchronous or early manifestation of liver metastases are poor prognostic factors

15. Suggestions after liver resection in case of short disease free interval
Strong follow up protocol of resected patients with intent to detect new manifestation of metastasis
Neoadjuvant, adjuvant chemotherapy

16. Prognostic factors for long term results– size of liver metastases
Controversial opinions:
Increasing tumor size – poor prognostic factor;
Iwatsuki S, Dvorchik I et al, J Am Coll Surg 189 : ,1999
Tumor size – no influence on survival;
Cady B, Jenkins RL et al Ann Surg 227: , 1998
Clinical consideration (hypothesis):
Large and solitary tumor because of long growing period should decrease likelihood of manifestation of new metastasis,
Current consensus:
There is no absolute metastasis size limit for surgical resection

17. Prognostic factors for long term results - margins
Studies:
Patients with positive resection margins ( noncurative) had a life expectancy similar to that of patients with unresectable disease;
Steele G Jr, Bleday R et al J Clin Oncol 9: , 1991
Patients with minimally negative microscopic margins (1 to 9 mm) compared to patients with margins greater than 10 mm:
1. decreased 5-year survival;
34% vs 41% (p = 0.009)
Scheele J., Stangl R. et al; World J Surg, 19:59-71,1995
23% vs 47% (p < 0.01)
Registry of Hepatic Metastases, Surgery, 103: , 1988
2. Increase in hepatic recurrence;
Hughes KS et al Surgery 100: , 1986

18. Obligations and Suggestions for surgeon in aspect of margins
to resect with minimally clear margins > 10mm
Suggestion-
To try expand clear margins to 30mm

19. Poor prognostic factors As guidelines for patient selection
Study
Age
Primary
Tumor Stage
No. of lesions
Size
Satellite lesions
Bilobar
Margins
(<1cm)
Disease
Free
Interval
CEA
Extra
Hepatic
disease
Fong
Iwatsuki
Lise
Cady Nordlinger
Jamison
Wanebo
Scheele
Doci +
>1
>2
>3
>5
>8
<1yr
<2,5yr
<2yr

20. Actuality of surgical resection (I)
Short term results

21. Short term results after liver resection
morbidity - <25%
mortality - <4%
Study
Mortality
Morbidity
Hepatobiliary
compl.
Infectious compl.
Scheele et al
Iwatsuki et al
Nordlinger et al
Cady et al
Fong et al
Doci et al
Our data 4% 1% 2% 3% -
16% 8%
23%
24%
18%
21% 6% 7% 9%

22. Morbidity and Mortality after liver resection
General complications:
cardiovascular, pulmonary, etc.
Infection, abscess;
Hemorrhage.
Specific complications:
bile leak, biliary fistula,
Liver failure
( can be decreesed < 5% with proper patient selection despite agresive surgical treatment).

23. Low morbidity and mortality depends on patient selection
Preoperative evaluation:
Medical condition
similar to other major abdominal surgery ( particular attention to pulmonary and cardiac systems).
2. Preoperative Hepatic function;

24. Main contraindication for expanded liver resection
Inability to preserve an adequate reserve of functional hepatic tissue;

25. Chance for survival after liver resection with normal liver function
70-75% of the liver can be resected without increasing the risk of postoperative liver failure in the absence of cirrhosis or fatty liver.
Sasson A.R., Sigurdson E.R. et al; Seminars in Oncology; Vol 29, No 2, 2002

26. Patient selection – preoperative evaluation of Hepatic function
Main question – extent of the operation?
Clinical evaluation (Child – Pugh);
Level of Bilirubinaemy;
Indocianine green (ICG-5);
CT volumetry.

27. Clinical evaluation (Child – Pugh) 1964mB C
Albuminaemy (g/l)
>35
30-35
<30
Bilirubinaemy (mkmol/l)
<40
40-35
>50
Ascites No
Easy control
Hard control
Encephalopathy
I – II
III – IV
Nutrition
Excelent
Good
Bad
Operation risk
Minimal
Medium
Big
Postoperative mortality
0-5 %
10-15 %
>25 %
1 year mortality
20-40 %
40-60 %

28. Liver resection volume guides
No ascites or easy control
Bilirubinaemy
normal
μmol/l
μmol/l
> 34.2 μmol/l
Limited
resection
Enucleation
Not resectable
ICG-5
normal
10-19%
20-29%
30-39%
> 40%
Major surgery
Bisegment-
ectomy
Segment-
ectomy
Limited
resection
Enucleation

29. CT volumetry of liver Liver sector Volume cm3 % Posterior 207.4 27.7
Anterior
149.9
19.7
Medial
163.3
21.5
Lateral
177.9
23.4
Caudal
22.7
2.9
Tumor
36.7
4.8

30. Preoperative procedures to increase volume of the liver
Decreasing of blood supply to diseased part of the liver with intent to enlarge normal liver lobe:
Portal vein embolisation
Embolisation of hepatic artery

31. Intent to enlarge normal liver before surgery
Transhepatic portal vein embolisation

32. Transileocolic portal vein embolisation scheme
Intent to enlarge normal liver before surgery
Transileocolic portal vein embolisation scheme
RPV
SMV
Laparotomy and catheterisation of ileocolic vein