Synchronous Hepatic Colorectal Metastases: Scope of the Problem Liver Disease Should be Resected First (with the primary tumor) • Colorectal cancer in USA • New cases 150,000 • Metastatic liver disease 75,000 20,000 * � Synchronous presentation 7,000 § � Liver-only disease * - may vary depending on definition used § - candidates for potentially curative resection William R. Jarnagin, MD, FACS Definitions Synchronous Colorectal Liver Metastases • Synchronous liver disease Historical approach • Identified at time of 1 o diagnosis � ? Within 12 months • Resect the primary lesion • Even if asymptomatic • Primary tumor � ‘To avoid bleeding or obstructive complications’ • Asymptomatic � No obstruction, no bleeding • Treat with chemotherapy • Liver disease • Infrequently consider surgery for the liver disease • Resectable with one procedure • ‘Synchronous disease carries a high risk for recurrence’ � Staged resection not required � ? Ablation plus resection • Not found incidentally during 1 o resection 1
Synchronous Colorectal Liver Metastases Synchronous Colorectal Liver Metastases Contemporary approach • Complete resection of all disease • The primary tumor • Should be the objective • Infrequently requires resection due to symptoms • Considered in the context of overall disease management • One operation is better than 2 • Chemotherapy • Morbidity/resource utilization related to both operations • Should be part of the treatment plan � Additive • Should not be a knee-jerk reflex to treat before resection � High risk patients likely to benefit most • All studies retrospective • Significant bias • Should always consider surgery if resectable • Synchronous disease does not preclude long-term survival • Colorectal resection first in nearly all staged procedures J Am Coll Surg 2009;208:842 Synchronous Colorectal Liver Metastases All patients Staged Synchronous (n=160) (n=70) p Pre-op Chemotherapy 70% 52% 0.001 • July 1997 – June 2008 Staged Synchronous � Lobe Resection 40% 47% 0.2 (n=160) (n=70) p LAR/APR/Total 35% 40% 1.0 Age (years) 61 58 0.06 • 230 patients with synchronous Complications Comorbidities liver metastases Overall 55% 56% 1.0 Cardiac 86% 87% 0.8 • Staged = 160 � Grade 3 21% 19% 0.5 Pulmonary 5% 3% 0.4 • Synchronous = 70 Mortality 2% 2% 1.0 Diabetes 10% 18% 0.2 Hypertension 33% 34% 1.0 OR time 235 min 180 min NS • Unmatched # Liver Tumors 3 (1-8) 3 (1-16) 1.0 EBL 350 ml 300 ml 0.9 Largest Size (cm) 4 (1-13) 3.7 (0.3-9) 1.0 • No differences Transfused 45% 50% NS Clinical Risk Score � 3 67% 64% 0.8 • Demographics Length of Stay 18 days 10 days 0.001 Rectal 1 o 23% 30% NS • Disease extent Martin et al. J Am Coll Surg 2009;208:842 2
Synchronous Colorectal Liver Metastases Major hepatic resections only Staged Synchronous (n=64) (n=33) p Complications • Consecutive synchronous Overall 60% 50% 0.6 Staged Synchronous � Grade 3 32% 15% 0.5 resections matched (n=32) (n=32) p Mortality 2% 0% 1.0 to staged procedures Age (years) 67 69 ns OR time 268 min 202 min 0.06 ASA 2 2 ns EBL 750 ml 450 ml 0.01 • Matching variables: Clinical Risk Score 2 2 ns Length of Stay 18 days 12 days 0.001 • Age LAR/APR 38% 38% ns � Lobe Resection • Gender 22% 22% ns • ASA Adjuvant/Neoadjuvant Tx 53% 41% ns • Hepatic resection • Similar results when only major hepatic resections considered • Primary resection Martin et al. J Am Coll Surg 2009;208:842 EJSO 2010;36:365 Synchronous Colorectal Liver Metastases Synchronous Colorectal Liver Metastases Major Author Years N Hepatectomy Morbidity Mortality Staged Synchronous Synch 73 73% 32% 0% (n=32) (n=32) p Yan et al - Staged 30 77% 43% 0% EBL 425 ml 475 ml ns Synch 28 32% 18% 0% Jaeck et al 1982-96 Staged 31 52% 16% 0% Morbidity 59% 34% 0.7 Synch 57 - 25% 3.5% Turrini et al 1994-05 Mortality 0 0 - Staged 62 - 21% 5.0% Length of Stay 20 days 12 days 0.008 Synch 31 - 19% 0% Stojanovic et al - Staged 51 - 20% 0% Synch 25 28% 0% Vassiliou et al 1996-04 NS Survival Staged 78 29% 0% Recurrence-Free 14 months 10 months 0.5 Synch 70 34% 33% 1% Capussotti et al 1985-04 Staged 57 56% 56% 0% Overall 42 months 39 months 0.8 5-Year 24% 21% 0.8 Synch 64 16% 53% 0% Chua et al 1996-99 Staged 32 41% 41% 0% Synch 39 13% 28% 0% Tanaka et al 1992-03 • Shorter hospital stay in synchronous group Staged 37 54% 16% 0% Synch 134 34% 48% 2% Martin et al 1984-01 • No difference in long-term survival Staged 106 72% 68% 2% Synch 35 31% 32% 0% Weber et al 1987-00 Staged 62 56% 23% 0% EJSO 2010;36:365 3
J Am Coll Surg 2013;216:707-716 J Am Coll Surg 2013;216:707-716 Surgical Management of Patients with Synchronous Surgical Management of Patients with Synchronous Colorectal Liver Metastasis: A Multicenter International Colorectal Liver Metastasis: A Multicenter International Analysis Analysis Skye C Mayo, MD, MPH, Carlo Pulitano, MD, Hugo Marques, MD, Jorge Lamelas, MD, Christopher L Wolfgang, MD, PhD, FACS, Skye C Mayo, MD, MPH, Carlo Pulitano, MD, Hugo Marques, MD, Jorge Lamelas, MD, Christopher L Wolfgang, MD, PhD, FACS, Wassila de Saussure, MD, Michael A Choti, MD, MBA, Isabelle Gindrat, MD, Luca Aldrighetti, MD, Eduardo Barrosso, MD, Gilles Wassila de Saussure, MD, Michael A Choti, MD, MBA, Isabelle Gindrat, MD, Luca Aldrighetti, MD, Eduardo Barrosso, MD, Gilles Mentha, MD, Timothy M Pawlik, MD, MPH, PhD, FACS Mentha, MD, Timothy M Pawlik, MD, MPH, PhD, FACS • 1,004 Patients with synchronous colorectal liver metastases Colorectal First Simultaneous Variable (n=647) (n=329) p • 1982 – 2011 Age (years) 61 60 ns • 4 Institutions Primary Colon 74% 72% ns • Treated with curative intent > 2 Liver Metastases 33% 35% ns � Resection + ablation of liver disease allowed Major Hepatectomy 39% 24% <0.001 � Extrahepatic metastases allowed if completely resected Resection + Ablation 11% 9% ns • Staged (colorectal first) = 647 Chemotherapy (pre or post) 63% 56% <0.001 • Staged (liver first) = 28 • Simultaneous = 329 J Am Coll Surg 2013;216:707-716 Surgical Management of Patients with Synchronous Colorectal Liver Metastasis: A Multicenter International Analysis Skye C Mayo, MD, MPH, Carlo Pulitano, MD, Hugo Marques, MD, Jorge Lamelas, MD, Christopher L Wolfgang, MD, PhD, FACS, Wassila de Saussure, MD, Michael A Choti, MD, MBA, Isabelle Gindrat, MD, Luca Aldrighetti, MD, Eduardo Barrosso, MD, Gilles Mentha, MD, Timothy M Pawlik, MD, MPH, PhD, FACS Colorectal First Simultaneous Variable (n=647) (n=329) p R0 Resection (liver) 72% 79% - • 610 patients over 21 years at 3 centers Severe Complications 11% 11% ns • Staged procedures done at same institution: 205 patients 90-Day Mortality 3.2% 2.7% ns • Simultaneous major hepatic resections: 36 patients Recurrence 60% 53% ns � < 1 patient per center per year • Staged and simultaneous resections: similar outcomes � Combined bias of 3 different institutions Ann Surg Onc 2007;14:3481 4
Synchronous Colorectal Liver Metastases Synchronous Colorectal Liver Metastases Liver first resection: Why? Staged Synchronous p MAJOR HEPATECTOMY • ‘Increasing complexity of care of 1 o colorectal cancers’ # 51 36 Length of Stay 14 days 9 days <0.0001 • Preoperative radiotherapy for rectal cancer Severe Morbidity 18% 36% 0.07 � Prevent progression of liver disease Mortality 0 8% 0.05 � Possibility of a complete response MINOR HEPATECTOMY # 19 99 • ‘Liver metastases give rise to widespread systemic disease’ Length of Stay 14 days 8.5 days <0.0001 Severe Morbidity 11% 14% 0.7 Mortality 0 1% 0.8 • ‘Option to give systemic therapy as a first step’ • Authors conclude: combined major hepatectomies should not be done • Questionable at best • Do these arguments mandate a paradigm shift? • Based on very small numbers (3 patients) � Accrued over a long time interval - Colorectal 1 st - Colorectal 1 st - Liver 1 st - Liver 1 st Colorectal Liver 1 st 1 st (n=58) (n=729) p Rectal 1 o 57% 23% <0.001 Pre-Colectomy XRT 31% 6% <0.001 Pre-Hepatectomy Chemo P = 0.96 P = 0.96 21% 4% <0.001 Irinotecan + Oxali 1 o Nodal Metastases 41% 72% <0.001 Clinical Risk Score � 3 • Liver 1 st approach: 51% 49% 0.2 • Survival similar to colorectal 1 st approach • Applicable to a very small fraction of all patients Ann Surg 2012;256:772 5
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