Staged Hepatectomy for Colorectal Metastases to Liver Dr. Steven, Kong Ling TING Caritas Medical Centre

Introduction Surgical resection is considered as a curative therapy for colorectal liver metastases (CLM) Surgical resection is considered as a curative therapy for colorectal liver metastases (CLM) 5-year overall survival rate - 58% 5-year overall survival rate - 58% Patient with unresectable colorectal liver metastases, and no other organs involved Patient with unresectable colorectal liver metastases, and no other organs involved Chemotherapy? Chemotherapy? Use of preoperative portal vein embolization and ablative therapies? Use of preoperative portal vein embolization and ablative therapies? Two stage hepatectomy (TSH) Two stage hepatectomy (TSH)

Selection of patients for resection of CLM: expert consensus statement. In Ann Surg Oncol 2006 Selection of patients for resection of CLM: expert consensus statement. In Ann Surg Oncol 2006 To preserve: To preserve: 1. two contiguous liver segments 1. two contiguous liver segments 2. adequate vascular supply and biliary drainage 2. adequate vascular supply and biliary drainage 3. adequate functional liver volume (FLV) >20% 3. adequate functional liver volume (FLV) >20% Unresectable disease – bilobar CLM, with inability to Unresectable disease – bilobar CLM, with inability to achieve margin negative (R0) resection of all tumors, achieve margin negative (R0) resection of all tumors, while preserving the above three criteria while preserving the above three criteriaIntroduction

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Past 5-year studies in PubMed and MEDLINE Past 5-year studies in PubMed and MEDLINE Two stage hepatectomy with curative intention Two stage hepatectomy with curative intention Initially unresectable disease Initially unresectable disease Survival outcomes reported Survival outcomes reported Overlapping patient pool series Overlapping patient pool series <10 patient number <10 patient number 9 Observational studies 9 Observational studies Review of Current Evidence

1. Bilobar multiple liver metastases 2. Response to chemotherapy 3. Adequate remnant liver volume (>25 / 30%) 4. Other conditions concerning surgical strategy, for example: left hemi-liver clear of metastases during 1st stage (Tsim et al.) Review of Current Evidence

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* R0 resection cases included only, DF = disease free Review of Current Evidence

Adjuvant modalities Adjuvant modalities Portal vein embolization Portal vein embolization Intra-operative ligation of portal vein Intra-operative ligation of portal vein ALPPS (Associating Liver Partition and Portal vein ligation for Staged hepatectomy) ALPPS (Associating Liver Partition and Portal vein ligation for Staged hepatectomy) Ablation (RFA) – preferably <1cm tumors away from major vessels Ablation (RFA) – preferably <1cm tumors away from major vessels Review of Current Evidence

Interval chemotherapy Interval chemotherapy Mentha et al. – histologic evidence supporting interval chemotherapy Mentha et al. – histologic evidence supporting interval chemotherapy Liver steatosis, steatohepatitis, sinusoidal liver injury, blue liver syndrome Liver steatosis, steatohepatitis, sinusoidal liver injury, blue liver syndrome Role of intra arterial chemotherapy (HAI) Role of intra arterial chemotherapy (HAI) Review of Current Evidence

Factors affect the survival outcome Factors affect the survival outcome Response to preoperative chemotherapy Response to preoperative chemotherapy FLR volume FLR volume Completion of both stages of hepatectomy Completion of both stages of hepatectomy Presence of extra-hepatic metastases Presence of extra-hepatic metastases ? Tumor number and size ? Tumor number and size ? Resection margin ? Resection margin Review of Current Evidence

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Two stage hepatectomy in selected patients with Two stage hepatectomy in selected patients with initially unresectable CLM is associated with initially unresectable CLM is associated with acceptable operative mortality and survival acceptable operative mortality and survival outcomes outcomes Consensus on patient selection, combined Consensus on patient selection, combined adjuvant modalities, interval chemotherapy adjuvant modalities, interval chemotherapy Data inhomogeneity: synchronous versus Data inhomogeneity: synchronous versus metachronous disease, use of biological agents, metachronous disease, use of biological agents, presence of extra-hepatic disease presence of extra-hepatic diseaseConclusion

Rees M, Tekkis PP, Welsh FKS, et al. Evaluation of long term survival after hepatic resection for metastatic colorectal cancer: a multifactorial model of 929 patients. Ann Surg : Rees M, Tekkis PP, Welsh FKS, et al. Evaluation of long term survival after hepatic resection for metastatic colorectal cancer: a multifactorial model of 929 patients. Ann Surg : Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol :1-34 Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol :1-34 Tanaka K, Shimada H, Ueda M et al. Perioperative complications after hepatectomy with or without intra-arterial chemotherapy for bilobar colorectal cancer liver metastases. Surgery : Tanaka K, Shimada H, Ueda M et al. Perioperative complications after hepatectomy with or without intra-arterial chemotherapy for bilobar colorectal cancer liver metastases. Surgery : Kuniya Tanaka, Takafumi Kumamoto, Kazunori Nojiri, et al. Timing of two stage liver resection during chemotherapy for otherwise unresectable colorectal metastases. World J Surg : Kuniya Tanaka, Takafumi Kumamoto, Kazunori Nojiri, et al. Timing of two stage liver resection during chemotherapy for otherwise unresectable colorectal metastases. World J Surg : Mohammad H. Jamal, Mazen Hassanin, et al. Staged hepatectomy for bilobar colorectal hepatic metastases. HPB : Mohammad H. Jamal, Mazen Hassanin, et al. Staged hepatectomy for bilobar colorectal hepatic metastases. HPB : Tsai S, Marques HP, et al. Two stage stretegy for patients with extensive bilateral colorectal liver metastases. HPB : Tsai S, Marques HP, et al. Two stage stretegy for patients with extensive bilateral colorectal liver metastases. HPB : Bowers KA, O’Reilly D, Bond Smith GE, et al. Feasibility study of two stage hepatectomy for bilobar liver metastases. Am J Surg : Bowers KA, O’Reilly D, Bond Smith GE, et al. Feasibility study of two stage hepatectomy for bilobar liver metastases. Am J Surg : Brouquet A, Abdalla EK, Kopetz S, et al. High survival rate after two stage resection of advanced colorectal liver metastases: response based selection and complete resection define outcome. J Clin Oncol : Brouquet A, Abdalla EK, Kopetz S, et al. High survival rate after two stage resection of advanced colorectal liver metastases: response based selection and complete resection define outcome. J Clin Oncol : Muratore A, Zimmitti G, Ribero D, et al. Chemotherapy between the first and second stages of a two stage hepatectomy for colorectal liver metastases: should we routinely recommend it? Ann surg Oncol : Muratore A, Zimmitti G, Ribero D, et al. Chemotherapy between the first and second stages of a two stage hepatectomy for colorectal liver metastases: should we routinely recommend it? Ann surg Oncol : Turrini O, Ewald J, et al. Two stage hepatectomy: who will not jump over the second hurdle? Eur J Surg Oncol : Turrini O, Ewald J, et al. Two stage hepatectomy: who will not jump over the second hurdle? Eur J Surg Oncol : Tsim N, Healey AJ, Frampton AE, et al. Two stage resection for bilobar colorectal liver metastases: R0 resection is the key. Ann Surg Oncol : Tsim N, Healey AJ, Frampton AE, et al. Two stage resection for bilobar colorectal liver metastases: R0 resection is the key. Ann Surg Oncol : Narita M, Jaeck D, et al. Two stage hepatectomy for multiple bilobar colorectal liver metastases. Br J Surg : Narita M, Jaeck D, et al. Two stage hepatectomy for multiple bilobar colorectal liver metastases. Br J Surg : Adam R, Wicherts DA, de Haas RJ, et al. Patients with initially unresectable colorectal liver metastases: is there a possibility of cure? J Clin Oncol : Adam R, Wicherts DA, de Haas RJ, et al. Patients with initially unresectable colorectal liver metastases: is there a possibility of cure? J Clin Oncol : Mentha G, Terraz S, Morel P, et al. Danerous halo after neoadjuvant chemotherapy and two step hepatectomy for colorectal liver metastases. Br J Surg : Mentha G, Terraz S, Morel P, et al. Danerous halo after neoadjuvant chemotherapy and two step hepatectomy for colorectal liver metastases. Br J Surg : Adam R, Pascal G, Castaing D, et al. Tumor progression while on chemotherapy: a contraindication to liver resection for multiple colorectal metastases? Ann Surg : Adam R, Pascal G, Castaing D, et al. Tumor progression while on chemotherapy: a contraindication to liver resection for multiple colorectal metastases? Ann Surg : Wicherts DA, Miller R, de Hass RJ et al. Long term results of two stage hepatectomy for irresectable colorectal cancer liver metastases. Ann Surg : Wicherts DA, Miller R, de Hass RJ et al. Long term results of two stage hepatectomy for irresectable colorectal cancer liver metastases. Ann Surg : Hemming AW, Reed AI, et al. Preoperative portal vein embolization for extended hepatectomy Ann Surg : Hemming AW, Reed AI, et al. Preoperative portal vein embolization for extended hepatectomy Ann Surg : Picture sources: Picture sources: