Cristino, H

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Synchronous liver metastases  Oncosurgical Strategy    How to resect the unresectable?  Humberto Cristino Diretor do Serviço de Cirurgia Geral: Dr. Mesquita Rodrigues Epidemiology Portugal *GLOBOCAN Report 2012 - International Agency for Research on Cancer • 7129 new cases of Colorectal Cancer *  • 1/3  are rectal cancers  • 3797 mortality cases* Epidemiology     25% of patients have metastatic disease at presentation    30% develop metastases during the course of their disease   The liver is the most common site of metastatic disease,   • Involved in 80 % of cases  • Liver-only mets (40 %)     Tzeng CW, Aloia TA. Colorectal liver metastases. J Gastrointest Surg. 2013  Frankel TL, D’Angelica MI. Hepatic resection for colorectal metastases. J Surg Oncol. 2014 Median survival – hepatic metastases    Untreated – survival   6 and 12 months    Systemic chemotherapy - median survival of 2-year     Resected R0 -  5 year survival ranges between 27% to 74%       - 10 Y survival 9- 50%      Results of hepatic resection for mets CCR n Survival  at 5 Years % median survival , M Hughes, KS; 1986 607 33 NR Scheele, J; 1995 434 33 40 Nordlinger, B; 1996 1568 28 NR Jamison, RL; 1997 280 27 33 Fong, Y; 1999 1001 37 42 Iwatsuki, S; 1999 305 32 NR Choti, M; 2002 133 58 NR Abdalla, E; 2004 190 58 NR Fernandez, FG; 2004 100 58 NR Wei, AC; 2006 423 47 NR Aloia TA; 2006 150 71 Rees, M; 2008 929 36 42.5 de Jong, M; 2009 1669 47 36 Morris, EJ; 2010 3116 44 NR    Resected R0 -  5 year survival ranges between 27% to 74%       - 10 Y survival 9- 50%      Resection is the only chance of long-term survival / cure     Only a minority of patients are suitable for upfront surgery 20% – 25%       When patients with unresectable disease are downstaged to complete resection, long-term data support 5 and 10-year survival are similar to upfront resectable patients       Liver metastases in colorectal cancer Liver metastases Resectable 20% to 25% Nonresectable 75% to 80% Survival benefit 27% to 74 % at 5 Y downstage Resectable 20% to 30% location number size FRL How to resect the unresectable?    Liver metastases in colorectal cancer “Resectable”      1. Appropriate medical candidate for surgery    2. The metastatic liver tumor can be completely resected.     3. Sufficient future remnant liver    Liver  Tumor  Patient Patient selection and Preoperative assessment   CT - scan of the abdomen and chest  MRI - if small lesions, a fatty liver or preop CT   PET - in case of tumor recurrence   - in patients with a previous liver resection   - suspected distant metastasis.    Child Pugh,   ICGR15   Tumor evaluation  liver function evaluation Two management strategies (to improve resectability.)   - Optimize the FLR  parenchymal-sparing liver surgery   PVE   two-stage hepatectomy  (ALPPS)  local ablation techniques       - Shrink tumors   Conversion chemotherapy,   Hepatic Arterial Infusion Pump Therapy    Liver  Tumor Strategies to Shrink Tumor Burden     Systemic Chemotherapy    Hepatic Arterial Infusion Pump Therapy  Systemic Chemotherapy   • In the 5-FU era -  response rates approximately 20 %      • Modern chemotherapeutic agents  (Oxaliplatin, Irinotecan … and new regimens FOLFOX, FOLFIRI …)   - tumor response rates of >50%   - 6-month stable disease 90–95 %   - long median survival (30 months).         • N= 872  • 701 patients with unresectable CRLM (80%)  • FOLFOX  • 14 % resectable         Ann Surg Oncol. 2001 5-year survival 39 % Tumor response rate -patients with unresectable CRLM Curr Oncol Rep (2014) 16:407    • Modern preop CT allows complete resection in 12-35% of patients   • A strong correlation between the response rates and the resection rates of patients with initially unresectable CLRM       Ressection conversion therapy -5 year OS (40–50 %)     -similar to upfront resectable patients  Hepatic Arterial Infusion Pump Therapy   The concept     • Liver mets larger than 3 mm over 80% of their blood irrigation is by hepatic artery   • Normal hepatocytes derive their blood supply from the PV (75%)    • The tip of the catheter is positioned at the gastroduodenal-hepatic artery junction    Surgery 1970;66:1067–1072 Hepatic Arterial Infusion Pump Therapy      • This directed therapy allows an increased amount of cytotoxic drugs without increasing the systemic side effects    • HAIP increased the possibility of tumor response and might improve liver function    • This therapy can be used in combination with systemic chemotherapy   Curr Oncol Rep (2014) 16:407    • 49 patients with unresectable CRLM   • combined HAIP and systemic CT including bevacizumab   • 47% achieved conversion to resection at a median of 6 months from treatment initiation  • 3-year OS – resected patients 80% / not resection26% Ann Surg. 2015 February ; 261(2): 353–360. Two management strategies (to improve resectability.)   - Optimize the FLR  parenchymal-sparing liver surgery   PVE   two-stage hepatectomy  (ALPPS)  local ablation techniques       - Shrink tumors   Conversion chemotherapy,   Hepatic Arterial Infusion Pump Therapy    Liver  Tumor Strategies to otimize FRL  The objective       parenchymal-sparing liver surgery   PVE   two-stage hepatectomy  (ALPPS)  local ablation techniques  Resection of all detectable lesions with tumor-free margins Preoperative Planning and  Volumetric Assessment   To achieve a safe hepatic resection with an adequate FLR    • Evaluation of the underlying parenchymal status and function   • Evaluation of liver tumors (the proximity to critical structures)   • Evaluation  of liver volumes (FRL)   Parenchymal-sparing liver surgery (One-Stage Ultrasonically Guided Liver Resection)      This technique allow radical but conservative liver resections   Avoiding the unnecessary sacrifice of functional parenchyma    Reducing the risk of developing postoperative liver failure   Avoiding the necessity of PVE / two stage heptectomy   with equal or better perioperative and long-term outcomes than non-PSLS    - A profound knowledge of liver patient’s anatomy  - Expert IOUS skills  World J Surg 2008; 32: 2057-2069        “Prophylactic” large resections were useless in preventing intra or extra-hepatic recurrence  • increased patient risk  • less chances of future repeated resection  • poorer prognosis after major resection than after multiple minor resections   Kokudo N; Am J Surg 2001; 181: 153-159 Tanaka K; World J Surg 2008; 32: 2057-2069 S7 resection S7 partial resection of RHV reconstruction by running suture S4a PVE (portal vein embolization)      Introduced in the 1980s by Makuuchi    Tumor is technically resectable but the FRL is too small    Is embolized the PV supplying the portion of liver to be resected   Induce ipsilateral atrophy and contralateral compensatory hypertrophy of the FRL up to 40% over a median period of approximately 4 weeks* *Azoulay, Ann. Surg. April 2000 Vol. 231, No. 4, PVE     Surgery         Surgery 2 to 6 weeks after PVE     Resectability 60% to 82%   - progression of hepatic or extrahepatic disease    - Insufficient hypertrophy 9%     Br J Surg. 2010 Feb;97(2):240-50. n = 364 hepatectomias major  PVE  = 67 (18%)  Morbilidade: 41 % não PVE / 55% PVE    61% 44% 0% PVE         PVE in bilobar disease      PVE may increases tumor growth rate       Kokudo N  et al, Hepatology, 2001;34:267-72. Two stage hepatectomy Two stage hepatectomy  In patients with bilobar, multinodular tumor       • the first stage - clearing the FLR  • PVE to increase the volume of the tumor-free FLR.   • second stage - resection of the remaining disease   The second stage resection is completed in 69-77% of patients **  Patients who complete two-stage procedure had an overall 5 Y survival of 42% **Oncology, Vol 5, No 5 October 2014  Annals of surgery 248, dec 2008 Two stage hepatectomy-strategy    Preop CT First-stage resection + PVE CT (3 w after liver resection) Second-stage resection Postop CT compensatory hypertrophy René Adam, MD, Ann Surg. 2000 December; 232(6): 777–785.  Two-Stage Hepatectomy: A Planned Strategy to Treat Irresectable Liver Tumors Wicherts, Ann Surg 2008;248: 994–1005) ALPPS - Associated Liver Partition and Portal vein ligation for Staged hepatectomy         • Is a novel two-stage technique for optimizing FLR  • First stage -Portal vein ligation is combined with an in situ liver transection  • Results in a pronounced short-term parenchymal hypertrophy over approximately 1 week  • Second stage (1 week), a second laparotomy  to remove the pre-divided liver   ALPPS - Associated Liver Partition and Portal vein ligation for Staged hepatectomy   • The increase in FLR with ALPPS ranges form  63-87%    • Advantage of ALPPS over PVE is the short interval to completion surgery    hypertrophy of the FLR - in less than   10 days (ALPPS)        - compared to over 3 weeks for PVE      Morbidity 53-71% /  mortality of 0-22%    The benefit of ALPPS over conventional PVE is heavily debated  J Gastrointest Oncol 2014;5(5):374-38 Locoregional Therapies - RFA     RFA thermally ablate tumors   Can be performed percutaneously, laparoscopically, or during laparotomy     Locoregional Therapies - RFA   Indications:   Patients who are not candidates for surgical resection (co-morbidities)    May be used in combination with resection in order to optimize FLR Journal of surgical oncology 2006;93:8-12 Locoregional Therapies - RFA   Disadvantage / limits        Tumors greater than 30 mm  (high recurrence rate)    Contact with major biliary structures (risk for bile duct stricture and fistula)    Contact with major vascular structures (risk of an inadequate ablation)       141 patients treated with multiple resections   95 patients treated with  ablation +  resection techniques   5-year OS was statistically similar - ablation-resection (56 %)         - multiple resection (49 %)   JAMA Surg. 2013 July ; 148(7): 597–601 What about liver tranplantation?  Nonresectable  liver-only metastases Standard treatment option  Palliative chemotherapy       comparison of results in 2 prospective studies SECA / NORDIC VII  - CRC nonresectable metástases  - liver-only metástases   SECA study - patients undergoing liver transplantation    NORDIC VII study  - patients receiving chemotherapy       - Nordic FLOX with or without cetuximab   Dueland et al Annals of Surgery Volume 261, Number 5, May 2015            5-year OS  -56% in patients undergoing liver transplantation -9% in patients starting firstline chemotherapy Dueland et al Annals of Surgery Volume 261, Number 5, May 2015     Autor recomendations    Selecting patients for liver transplantation based on   • CEA <80 μg/L • metastases < 5.5 cm • no progressive disease at the time of transplantation • more than 2 years from diagnosis of CRC   May be obtained a 5-year OS rate of 75% Liver metastases in colorectal cancer Liver metastases Resectable 20% to 25% Nonresectable 75% to 80% Survival benefit 27% to 74 % at 5 Y downstage Resectable 20% to 30% Surgical techniques  Medical therapies Conclusion   • Surgical resection remains the treatment of choice for resectable CLM   • Surgical techniques and medical therapies, are currently utilized in to improve resectability.   • Treating hepatic metastases requires a knowledge of all treatment options   • Patients with unresectable disease are downstaged to complete resection, long-term data support 5 and 10-year survival are similar to upfront resectable patients   • Liver Transplantation for Unresectable CRCLM? … Obrigado   Humberto Cristino Diretor do Serviço de Cirurgia Geral: Dr. Mesquita Rodrigues 

Synchronous liver metastases, oncosurgical strategy: How to resect the unresectable?

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Synchronous liver metastases, oncosurgical strategy: How to resect the unresectable?

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