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The latest changes in surgery of liver metastatic colorectal cancer. Preoperative evaluation of the patient with hepatic metastases Treatment of liver metastatic colorectal cancer Surgical, chemotherapy and biological.

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General Information Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the United States. CRC is the second-most common cause of cancer death in western countries.

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In approximately 50% of patients with CRC liver metastatic, the metastatic disease is confined to the liver. The liver is the most frequent site of metastasis in CRC, both at the time of diagnosis (2025% of cases) or after an apparently radical surgery on the primary tumor (40% of cases).

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0 1 2 3 4 5 100 50 0 % surviving Years after diagnosis of colorectal metastases 3% 19881998 Rougier P et al. Brit J Surg 1995 1928 0% 1943 First hepatectomy for colorectal liver metastasis 1957 Introduction of 5-fluorouracil

The Benefits and Side effects of Surgery Recent reports- 5 years overall survival >28%. Low mortality-1.5% (high volume), and 9.6% (low volume) but higher morbidity- 15-30% : hemorrhage, abscess, bile leaks, hepatic failure.

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Hepatic resection for colorectal metastases, limited to the liver, has become the standard of care. Surgery currently remains the only potentially curative therapy.

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Multidisciplinary approach Patient Surgeon Oncologist Gastroenterologist Anaesthesiologist radiologist

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Preoperative Evaluation of the Patient with Hepatic Metastases Easily resectable disease Initially unresectable disease Unresectable

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Defining Resectability Criteria for surgery Imaging.

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Old approach criteria for surgery(1989, Steele et al): Less then four lesions in the same lobe. Maximum lesion dimensions

Current approach for liver surgery New approach criteria for surgery(2006,Vauthey et al): Complete Radical resection(less then 1cm margin). Preservation of two adjacent liver segments. adequate vascular inflow and outflow and biliary drainage can be preserved Future liver remnant(total volume>20%). Aggressive approach More then one hepatectomy Resecting metastases in other sites as well(lungs, adrenal etc)

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Contra-indications: Radiographic evidence of involvement of the common hepatic artery, common hepatic or common bile duct, or main portal vein Extensive liver involvement (>70 percent, more than six segments, or involvement of all three hepatic veins) Inadequate predicted post resection functional hepatic reserve

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Normal Underlying Liver 20% of TLV Kubota, Hepatology 1997 Azoulay, Ann Surg 2000 Abdalla, Arch Surg 2002 Vauthey, Ann Surg 2004 High Dose Chemotherapy 30% of TLV Chronic Liver Disease 40% of TLV Azoulay, Ann Surg 2000 Adam, Ann Surg 2004 Liver Remnant Volume

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Liver Volumetry

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Minimized the postoperative mortality- preserving a liver remnant that is >20% of the total liver volume. pre-operative portal vein embolization (PVE) to initiate compensatory hypertrophy of the future remnant liver. Atrophy of embolized lobe. Hypertrophy of non embolized lobe- Increasing Remnant liver. More potential surgical candidates Preoperative portal vein embolization

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Imaging CT CT is the staging modality most widely used in CRC Widespread availability and relatively low cost in comparison with MRI or PET/CT. In a study with surgically proven liver lesions, a sensitivity of 69% to 73% and a specificity of 86% to 91% was shown.* Limitations: steatosis, lesions smaller than 1 cm, Hemangiomas. *Kamel et el.J comput 2003, Kinkel et el. Radiology 2002, Bhattacharjya et al.Br J Surg. 2004.

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Imaging FDG-PET/CT Evaluation of patients with known or suspected recurrent colorectal cancer. Most sensitive method for detecting extra-hepatic disease in patients with CLM. Alters surgical management in 23% to 29% of patients. Measures the responsiveness of the tumor to preoperative treatment. For hepatic lesions compared with CT, it has a Sensitivity - 91100 % and Specificity- 75-100% (Patel S et el. Ann Surg 2011). Limitations: Correlation of pathological response and metabolic response, detecting lesions smaller than 1 cm, expansive.

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Imaging MRI Sensitivity 81.1% and specificity of 97.2%. mangafodipir trisodium imaging has a sensitivity of 100%, a specificity of 92%. Better sensitivity with patients that have steatosis, lesions smaller than 1cm. Best preoperative imaging technique for CLM detection, but not used routinely. Used to differentiate metastatic findings from benign findings such as- cysts, adenomas, and hemangiomas. Limitations: length of the scan time, patient compliance and higher costs.

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Imaging US Widespread availability. Sensitivity is in the range of 36 to 61% in small liver lesions. Limitations: lesions> 2cm, experience of the operator, impaired accuracy with: obese patients, liver steatosis. Used for surveillance and liver lesion biopsy.

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Imaging- Intraoperative US Intraoperative US- most sensitive technique for detecting liver lesions (sensitivity 93 to 94%). Discovers 25 30 % new lesions. May change planning of the operation.

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Imaging- Summary CT scan is an essential tool in the optimal imaging of the majority of CLM. MRI : for patients with liver damage owing to prolonged treatment or co-morbidities. For lesions smaller than 1cm, the sensitivity estimates for MRI were higher than those for CT. (Niekel et al 2010). PET/CT is extremely useful to exclude extrahepatic disease. Intraoperative evaluation by IOUS, mandatory in all patients undergoing surgical resection of CLM.

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Overall survival in advanced colorectal cancer in 2008: The impact of multi-disciplinary management 0 1 2 3 4 5 100 50 0 % surviving Years after diagnosis of colorectal metastases 2008 chemotherapy Median survival >24 months 5 year survival 9 % 3%

Radiofrequency ablation (RFA) Needle probe under image guidance generating heat and thus destroying the interstitial. Temperatures >60 results in cell necrosis

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Others Cryosurgery Yittrium 90

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Hepatic resection for colorectal metastases that are limited to the liver is a standard of care. Preoperative Evaluation of the Patients is vital. Each patient needs a different care. The future is promising.

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