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Surgical Approach To Liver Metastases from Colorectal Cancer

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The topics of this lecture: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.

2General InformationColorectal 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.

3In 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).

Time of diagnosis synchronous. After radical surgery- metachronous4 0 1 2 3 4 5100500% survivingYears after diagnosis of colorectal metastases3%19881998Rougier P et al. Brit J Surg 199519280%1943 First hepatectomy for colorectal liver metastasis 1957 Introduction of 5-fluorouracil28%.

Low mortality-1.5% (high volume), and 9.6% (low volume) but higher morbidity- 15-30% : hemorrhage, abscess, bile leaks, hepatic failure.

Low volume- less than eight resections per year.Even 10 yrs survival studies morbidity with liver resection includes hemorrhage, perihepatic abscess, bile leak and/or fistula, pleural effusion, and hepatic failure.patients undergoing resection, with 5-year overall survival exceeding 50%. Median survival in unresected- 6-9 months.7Hepatic 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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10Multidisciplinary approachTumor board.. And all thatSocial worker.11Preoperative Evaluation of the Patient with Hepatic Metastases

easily resectable disease =those cases with a few CLM, which can be easily resected patients with unresectable disease -extensive or ill-located tumor unresectable even with treatment Approximately 1015% of patients with CLM are considered resectable at the time of diagnosis12Defining ResectabilityCriteria for surgeryImaging.

13Criteria for surgery

14Old approach criteria for surgery(1989, Steele et al):Less then four lesions in the same lobe.Maximum lesion dimensions20%).Aggressive approachMore then one hepatectomyResecting metastases in other sites as well(lungs, adrenal etc)Vauthey JN, Choti MA, Helton WS. AHPBA/SSO/SSAT consensus conference on hepatic colorectal metastases: rationale and overview of the conference. Ann. Surg. Oncol.13,12591260 (2006).It is worth noting that R0 resection is defined independently of the surgical margin width, which can be less than 1 cm with no impairment in survival, provided that all of the tumor is removed. [39,40] Moreover, in the event that the remnant liver will be not sufficient after the planned surgical procedure, innovative approaches, such as preoperative portal vein embolization (resulting in subsequent hypertrophy of future liver remnant) and staged hepatic resection [41] may offer the possibility to reconsider a larger percentage of mCRC patients for metastasectomy. In contrast, patients with cirrhosis need a greater remnant liver volume (>40%) in order to avoid postoperative liver failureno strong evidence to date has clearly demonstrated improved outcomes following PVE compared to no PVE16Contra-indications:Radiographic evidence of involvement of the common hepatic artery, common hepatic or common bile duct, or main portal veinExtensive 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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Also in doubt what about artificial IVC OR PORTAL TRIADS??18Normal Underlying Liver20% of TLVKubota, Hepatology 1997Azoulay, Ann Surg 2000Abdalla, Arch Surg 2002Vauthey, Ann Surg 2004High Dose Chemotherapy30% of TLVChronic Liver Disease40% of TLVAzoulay, Ann Surg 2000Adam, Ann Surg 2004Liver Remnant Volume19And 40% for patients with chronic liver disease or who have undergone high dose chemotherapy.Liver Volumetry

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

Preoperative portal vein embolization -. PVE results in marked atrophy of the embolized lobe due to the reductionn blood flow through. In contrast, portal venous flow to the non-embolized lobe increases because venous return from the splanchnic system is essentially unchanged which has an overall effect of inducing marked hypertrophy of the non embolized lobe.Modern multimodality approach to hepatic colorectal metastases: Solutions and controversies Vijay P. Khatri el al (2007 surgical oncology).(A) Patient with CLM who required a right hepatectomy but had a small left hepatic lobe (outlined), (B) angiogram showingright posterior and anterior portal vein embolization with coils and glue (arrows), (C) left hepatic lobe hypertrophy (outlined) seen,(D) CT Scan following right hepatectomy and the patient recovered without liver failure.

21Imaging

Imaging CTCT 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.

When CT is used in the staging of patients for cancer metastatic lesions, the use of intravenous contrast is mandatory and examination should be perfomed by multiphasic technique with a minimum of thin slices defined as at least 2.5-mm cuts.Metastases appear hypovascular(BLACK) to the surrounding liver parenchyma. Getting livers hepatic artery supply.. A recent meta-analysis, collecting the data from a pool of 12 articles investigating the role of helical CT, reported a sensitivity of 74.8% on a per-patient basis and 82.6% on a per-lesion basis. [13] In a meta-analysis of hepatic metastases from cancers of the gastrointestinal tract, Kinkel et al (14) reported a mean weighted sensitivity of 72% for CT based on 25 publications that included 1,747 patients. In another study with surgically proven liver lesions, a sensitivity of 69% to 71% and a specificity of 86% to 91% was shown using dual-phase helical CT.(8)For metastatic colorectal carcinoma,a sensitivity of 73% and specificity of 96.5% was reported.

8. Kamel IR, Georgiades C, Fishman EK. Incremental value of advanced image processing of multislice computed tomography data in the evaluation of hypervascular liver lesions. J Comput Assist Tomogr. 2003;27:652-65614. Kinkel K, Lu Y, Both M, et al. Detection of hepatic metastases from cancers of the gastrointestinal tract by using noninvasive imaging methods (US, CT, MR imaging, PET): a meta-analysis. Radiology. 2002;224:748-756.15. Bhattacharjya S, Bhattacharjya T, Baber S, et al. Prospective study of contrast-enhanced computed tomography, computed tomography during arterioportography, and magnetic resonance imaging for staging colorectal liver metastases for liver resection. Br J Surg. 2004;91:1361-1369.23Imaging FDG-PET/CTEvaluation 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.

HIGH CEA.The use of PET/CT in the imaging of CLM is also currently evaluated for its potential for measuring the responsiveness of the tumor to preoperative treatment, as measured by the therapy-induced reduction of FDG uptake: this represents a positive sign to the surgeon performing resections of CLM.FDG-PET proved to be the most sensitive method for detecting extrahepatic disease in patients with CLM, leading to changes in the surgical management of patients in 25% of cases, with a reduction of nontherapeutic laparotomies.More recently, Patel and colleagues identified six studies over 440 patients comparing CT scan and PET/CT, and confirmed that for extrahepatic lesions PET/CT was more sensitive than CT (7589 vs 5864%, respectively), with similar specificities (9596 vs 8797%, respectively). [17] With regards to CLM, PET/CT was superior than CT both for sensitivity (91100 vs 7894%, respectively) and specificity (75100 vs 2598%, respectively), and the same results were reported for local recurrences.Imaging of the entire body with PET permits the diagnosis of unsuspected metastases outside of the liver and alters surgical management in 23% to 29% of patients.Patel S, McCall M, Ohinmaa A et al. Positron emission tomography/computed tomographic scans compared to computed tomographic scans for detecting colorectal liver metastases: a systematic review. Ann. Surg.253,666671 (2011). most accurate for detection of hepatic metastases greater than 1 cm in diameter.

24Imaging MRISensitivity 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.

moreover, it is likely that the accuracy of MRI will be further improved in coming years thanks to the availability of new hepatocyte-specific contrast agents (e.g., gadoxetic acid disodium) that are selectively taken up by hepatocytes with a complete wash-out in metastatic lesions.25Imaging USWidespread 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.

should be carefully considered when chosen as the preferred imaging modality for CLM, particularly in the case of small liver lesions (2 cm or less in maximum diameter) when sensitivity is in the range of 36 to 61%.

26Imaging- Intraoperative USIntraoperative US- most sensitive technique for detecting liver lesions (sensitivity 93 to 94%).Discovers 25 30 % new lesions.May change planning of the operation.

intraoperative US (IOUS) is, the most sensitive technique for detecting liver lesions (sensitivity 93 to 94%), but its invasive nature limits its use.

27Imaging- SummaryCT 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.In a recent meta-analysis by Niekel et al., a total of 3391 patients from 39 studies were analyzed in order to define the diagnostic performance values of different imaging techniques in the detection of CLM in patients who have not previously undergone therapy. [22] FDG-PET achieved a higher sensitivity estimate compared with CT and MRI, while specificity estimates were comparable among different methods. Interestingly, authors found that, for lesions smaller than 10 mm, the sensitivity estimates for MRI were higher than those for CT, while no differences were detected for lesions of 10 mm or more. Therefore, MRI is recommended by the authors as the preferred first-line modality for evaluating CLM in untreated patients, while FDG-PET can be used as the second-line modality.(Niekel MC, Bipat S, Stoker J. Diagnostic imaging of colorectal liver metastases with CT, MR imaging, FDG PET, and/or FDG PET/CT: a meta-analysis of prospective studies including patients who have not previously undergone treatment. Radiology257,674684 (2010). )

To conclude, CT scan is an essential tool in the optimal imaging of the majority of CLM. MRI may provide additional benefit in terms of accuracy, particularly when the performance of CT is impaired by important liver damage owing to prolonged treatment or concomitant co-morbidities. PET/CT is extremely useful to exclude extrahepatic disease, but its value in patients with liver-only metastases has not been definitively demonstrated.Finally, no preoperative technique may substitute the intraoperative evaluation by IOUS, which remains mandatory in all patients undergoing surgical resection of CLM.

28Treatment of liver metastatic colorectal cancer

Overall survival in advanced colorectal cancer in 2008: The impact of multi-disciplinary management 0 1 2 3 4 5100500% survivingYears after diagnosis of colorectal metastases2008 chemotherapyMedian survival >24 months 5 year survival 9 % 3%