Surgery of colorectal liver metastasis Juozas Pundzius Surgery 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.

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

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 607 434 1,568 280 1,001 305 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, 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, 103:278-288, 1988

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?

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 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 Oncol7:643-650, 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 to resect with minimally clear margins > 10mm Suggestion- To try expand clear margins to 30mm

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

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% 3% - 16% 8% 23% 24% 18% 21% 6% 7% 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: 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 B 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 %

Liver resection volume guides No ascites or easy control Bilirubinaemy normal 18.8-25.6 μmol/l 27.4-32.5 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

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