Surgery of colorectal liver metastasis

Juozas PundziusSurgery clinic of Kaunas university of

medicine

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.

Sasson A.R., Sigurdson E.R. et al; Seminars in Oncology; Vol 29, No 2, 2002

Methods of treatment of liver metastasis

CurativeSurgical – 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

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. 137:156-163, 2005

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

1999

607

434

1,568

280

1,001

305

33%

33%

28%

27%

37%

32%

-

40

-

33

42

-

Long term results – our data

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).

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 230:309-318, 1999Elias 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, 103:278-288, 1988

Restrictions for surgery in case of extrahepatic disease

Liver resection restricted in:1. Presence of metastasis in two or more organs -

lung, liver, colon (recurence) in case of multiple metastasis in one of them

2. Carcinomatosis, pleuritis, ascitis

3. Presence of portal or celiac lymph node metastasis proved by biopsy and extra pathology?

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 1.001 patients);

Fong Y, Fortner J et al Ann Surg 230:309-318, 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 77:1254-1262,1996

Suggestions for therapy in case of primary tumor spread

Node positive patients – candidates for adjuvant therapy

Prognostic factors for long term results– number of liver metastases

Increasing number of metastases – decreasing survivalExperience-

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 Oncol7:643-650, 2000

Statement- increased number of metastasis increasing likelihood of

undetectable metastasis

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

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 230:309-318, 1999

Synchronous or early manifestation of liver metastases are poor prognostic factors

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

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 :291-299,1999

Tumor size – no influence on survival;Cady B, Jenkins RL et al Ann Surg 227:566-571, 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

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 9:1105-112, 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, 103:278-288, 1988

2. Increase in hepatic recurrence;Hughes KS et al Surgery 100:278-284, 1986

Obligations and Suggestions for surgeon in aspect of margins

Obligation- to resect with minimally clear margins > 10mm

Suggestion-To try expand clear margins to 30mm

Poor prognostic factorsAs 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

>1

>3

>3

>3

>5

>8

>3

>5

>5

+

+

+

+

+

+

+

+

+

<1yr

<2,5yr

<2yr

+

+

+

+

+

+

+

Actuality of surgical resection (I)

Short term results

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%

4%

3%

2%

-

16%

8%

23%

-

24%

18%

21%

8%

-

-

3%

4%

6%

7%

3%

-

-

6%

6%

8%

9%

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).

Low morbidity and mortality depends on patient selection

Preoperative evaluation:

1. Medical condition similar to other major abdominal surgery ( particular attention to pulmonary and cardiac systems).

2. Preoperative Hepatic function;

Main contraindication for expanded liver resection

Inability to preserve an adequate reserve of functional hepatic tissue;

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

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.

Clinical evaluation (Child – Pugh) 1964m

A B C

Albuminaemy (g/l) >35 30-35 <30

Bilirubinaemy (mkmol/l) <40 40-35 >50

Ascites No Easy control

Hard control

Encephalopathy No I – II III – IV

Nutrition Excelent Good Bad

Operation risk Minimal Medium Big

Postoperative mortality 0-5 % 10-15 % >25 %

1 year mortality Minimal 20-40 % 40-60 %

No ascites or easy control

Bilirubinaemy

normal 18.8-25.6 μmol/l 27.4-32.5 μmol/l > 34.2 μmol/l

Limitedresection

Enucleation Not resectableICG-5

normal 10-19% 20-29% 30-39% > 40%

Major surgery

Bisegment-ectomy

Segment-ectomy

Limited resection

Enucleation

Liver resection volume guides

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

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

Intent to enlarge normal liver before surgery

• Transhepatic portal vein embolisation

Transileocolic portal vein embolisation scheme

Laparotomy and catheterisation of ileocolic vein

RPV

SMV

Intent to enlarge normal liver before surgery