How to deal with synchronous primary and liver metastases

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1 How to deal with synchronous primary and liver metastases Luis Sabater Ortí MD, PhD Associate Professor University of Valencia European Board Surgical Qualification HBP (EBSQ-HPB) Department of Surgery. Liver-Biliary and Pancreatic Unit Hospital Clínico. University of Valencia

2 DISCLOSURE Nothing to disclose

3 Painting: Sandra Villa Lago Photograph: David Gimeno Veses School of Medicine. Universitat de Valencia

4 Definitions SYNCHRONIC Metastasis Diagnosed at the same time as the CRC Pre-operative staging Intraoperative finding (urgent surgery CRC) 3-6 months after resection % of patients with CRC SIMULTANEOUS SURGERY (Vogt P, 1991) SEQUENTIAL BOWEL-FIRST (80s and two-staged in 2000, Adam R) SEQUENTIAL LIVER FIRST (Mentha G, 2006)

5 Definitions, advantages and disadvantages Simultaneous: All liver metastases and the primary tumor are resected in the same operation Advantages Avoid two operations Beneficial psycological effects Resection of all disease, lower risk of dissemination Chemo starts early and in better oncological conditions Less morbidity Shorter length hospital stay Lower costs Disadvantages Long surgical time Specialised surgeons required The biological behaviour of the tumor is not observed Safety of bowel anastomosis Higher risk of occult liver metastases Bacterial contamination Infection / sepsis

6 Definitions, advantages and disadvantages Sequential bowel-first: First resection of the CRC and then the liver metastases. With or without Chemo during the interval. Advantages Less surgical time for each surgical operation No accumulation of risks in each surgery Better management of complex surgeries Allows evaluation of tumor behaviour With Chemo occult liver M1 or microm1 are treated With Chemo reduces M1 size: less parenchyma resection and higher R0 Evaluation response to Chemo and tolerance Less recurrence rate (?) Disease free survival longer (?) Disadvantages Two surgical operations Psychological effects Longer length of hospital stay If complications, delays liver surgery or Chemo Increase in morbidity If interval Chemo, toxicity may appear If interval Chemo, M1 can disappear Disease progression Unresectability Higher costs

7 Definitions, advantages and disadvantages Sequential bowel-first: Resection of the primary CRC and clearance of the less invaded liver. Then, complete resection of the liver metastases (after hypertrophy of the FLR) PORTAL Embolization

8 Definitions, advantages and disadvantages Sequential liver first (reverse approach): Resection first of all liver metastases and later the CRC. Always neoadjuvant chemo. Rationale 1 : the lesion that kills the patient is the metastasis Rationale 2: progression of the CRLM beyond resectability during treatment of the primary tumour, especially if delay is due to complications of primary resection or adjuvant chemotherapy. Advantages Chemo treatment of liver metastases and the primary CRC Avoids progression of liver metastases Allows the most appropriatte timing of administration of pelvis Chemo-RDT Early administration of Chemo Increase S if conversion of M1 to resectables Avoids palliative surgery of CRC and its complications Disadvantages Liver progression in cases of doubtful resectability with non-response to Chemo CRC progression (rare) Complications of primary CRC requiring urgent or palliative surgery (5-11 %) Long liver toxicity Small size liver M1 disappearance Short surgical window (6-12 months)

9 Scientific Evidence. Review Simultaneous liver & primary versus sequential Hillingso JG, Wille-Jorgensen P. Staged or simultaneous resection of synchronous liver metastases from colorectal cancer- a systematic review. Colorectal Disease 2009; 11:3-10 Brouquet A, Mortenson MM, Vauthey J-N et al. Surgical Strategies for Synchronous Colorectal Liver Metastases in 156 Consecutive Patients: Classic, Combined or Reverse Strategy? J Am Coll Surg 2010; 210: Slesser AAP, Simillis C, Goldin R, Brown G, Mudan S, Tekkis PP. A meta-analysis comparing simultaneous versus delayed resections in patients with synchronous colorectal liver metastases. Surgical Oncology 2013; 22: Baltatzis M, Chan AK, Jegatheeswaran S, Mason JM, Siriwardena AK. Colorectal cancer with synchronous hepatic metastases: Systematic review of reports comparing synchronous surgery with sequential bowel-first or liver-first approaches. Eur J Surg Oncol 2016; 42: Abelson JS, Michelassi F, Sun T, Mao J, Milsom J, Samstein B, Sedrakyan A, Yeo HL. Simultaneous resection for synchronous colorectal liver metastases : the new standard of care? J Gastrointest Surg 2017; 21:

10 Scientific Evidence. Review Simultaneous liver and primary versus sequential Hillingso JG, Wille-Jorgensen P. Staged or simultaneous resection of synchronous liver metastases from colorectal cancer-a systematic review. Colorectal Disease 2009; 11: studies, Biases (prevent meta-analysis): simultaneous more frequent in right colon Tm and limited resections sequential more frequent in bigger and multiple M1 Simultaneous surgery Sequential surgery Length of Hospital Stay 15 days 18 days Morbidity 33 % 42 % Mortality 3.6 % 1 % Survival = =

11 Scientific Evidence. Review Sequential LIVER FIRST Brouquet A, Mortenson MM, Vauthey J-N et al. Surgical Strategies for Synchronous Colorectal Liver Metastases in 156 Consecutive Patients: Classic, Combined or Reverse Strategy? J Am Coll Surg 2010; 210: Sequential Colon first N= 72 Simultaneous Colon & Liver N= 43 Sequential Liver first N= 27 Morbidity 51 % 47 % 31 % p NS Mortality 3 % 5 % 4 % p NS Survival (3, 5 years) 58 %, 48 % 65 %, 55 % 79 %, 39 % p NS Nº M p < 0.05 Major Hepatectomy 66 % 35 % 89 % p< 0.05 Sequential Liver First 5 % complications related to primary tumour 34 % do not complete primary tumour resection

12 Scientific Evidence. Review Simultaneous liver and primary versus sequential Slesser AAP, Simillis C, Goldin R, Brown G, Mudan S, Tekkis PP. A meta-analysis comparing simultaneous versus delayed resections in patients with synchronous colorectal liver metastases. Surgical Oncology 2013; 22: studies, : 3159 patients: 1381 Simultaneous (43.7 %) 1778 Sequential (56.3%) Biases: < Neoadjuvant Chemo in simultaneous More frequent bilobar and bigger M1 in sequential and higher rate of major resections in sequential Simultaneous surgery Sequential surgery Length of Hospital Stay 14 days 20 days Time of surgery = = Blood loss = 825 ml = 955 ml Free disease survival = = Survival = = Morbidity = 36 % = 37 %

13 Scientific Evidence. Review Simultaneous liver and primary versus sequential Baltatzis M, Chan AK, Jegatheeswaran S, Mason JM, Siriwardena AK. Colorectal cancer with synchronous hepatic metastases: Systematic review of reports comparing synchronous surgery with sequential bowel-first or liver-first approaches. Eur J Surg Oncol 2016; 42: studies, : 1203 patients: 748 Bowel first (62%) 380 Simultaneous (31.5%) 75 Liver first (6.5%) Minor complications similar Major complications : 9.1 % (95%CI: 7.6%-10.8%, I 2 =48%) Death: 3.1 % (95%CI: 2.2%-4.3%, I 2 =0%) 5-year survival 44% (I 2 =39%) Overall treatment-related mortality is low and survival is similar among the 3 groups.

14 Scientific Evidence. Review Simultaneous liver and primary versus sequential 135 Hospitals New York State Abelson JS et al. J Gastrointest Surg 2017

15 Scientific Evidence. Review Simultaneous liver and primary versus sequential Abelson JS et al. J Gastrointest Surg 2017

16 Scientific Evidence. Review Sturesson Ch et al. Liver-first strategy for synchronous colorectal liver metastases-an intention-to treat analysis. HBP 2017; 19: Liver-first 35 % Do not complete the planned treatment (two surgeries) Classical 30 % Do not complete the planned treatment (two surgeries)

17 Scientific Evidence. Review SIMULTANEOUS vs Sequential BOWEL FIRST vs Sequential LIVER FIRST Summary Scientific Evidence None randomized (RCT) studies Important selection biases Sequential in patients with greater liver disease No clear evidence Simultaneous and sequential resections are equally feasible and safe in selected cases Simultaneous short length of hospital stay and same survival Liver first approach is an option in patients with synchronous M1 and asymptomatic primary tumour Despite having greater metastatic disease, same survival as the simultaneous or bowel-first approach

18 Indications and clinical recommendations SIMULTANEOUS Surgery Patients with good general condition who can withstand the 2 procedures (colon and liver) (longer time and greater aggressiveness) High possibility of R0 resection in both fields (no matter the number, size or location of M1) Sufficient liver remnant (25-40%) (2 contiguous segments with their vascular pedicles and biliary drainage) No extrahepatic disease or resectable (pulmonary metastases) Uncomplicated primary tumor: no occlusion, no perforation, no hemorrhage Specialized surgeons and estimated surgery times <6 hours (variable) Do not associate complex surgeries in the two fields

19 Indications and clinical recommendations SIMULTANEOUS Surgery During surgery, reevaluate if continue with the 2 procedures (safety) No peritoneal spread No severe complications during the first resection Resection of all metastases seen on intraoperative ultrasound First liver metastases or first colorectal tumor? 1º liver: Liver surgery without contamination Work with low PVC (<5 mmhg) without affecting this hypovolemia to the colorectal anastomosis Avoid colon edema (on the anastomosis) by Pringle 1º CRC: R0 safety in the primary Pringle manouvre as short as posible (only if necessary)

20 Indications and clinical recommendations SEQUENTIAL COLON FIRST Surgery Patient with comorbidities that prevent 2 simultaneous surgeries Surgeon who is not an expert in liver surgery Doubtful resectability (R0) or unresectability of M1 or CCR Very long estimated surgical time Complex surgery of the CRC and the M1 Complicated CRC: obstruction, perforation... Bilobar metastases, adjacent to large vessels or liver remnant <25-40% Extrahepatic metastases

21 Indications and clinical recommendations SEQUENTIAL LIVER FIRST Surgery Asymptomatic primary tumor or minimal symptoms (treatable by endoscopy) Unresectable or borderline resectable liver M1 M1 hepatic and extrahepatic unresectable or doubtfully resectable (initially) Hepatic M1 of doubtful resectability with uncomplicated primary but doubtful resectability with oncological criteria Large or multiple liver M1 at risk of becoming unresectable if they progress after resection of the primary

22 Synchronous primary CRC and liver metastases Trends in surgical strategy Vallance AE et al. The timing of liver resection in patients with colorectal cancer and synchronous liver metastases: a population-based study of current practice and survival. Colorectal Dis 2018

23 Synchronous primary CRC and liver metastases Management of the disappearing metastases (after chemotherapy) Incidence: 5-38 % MRI more accurate than CT for detecting lesions after chemo Try to avoid this problem Early involvement of surgeon: Multidisciplinary board Limit the duration of chemo: short course or stop when response allow surgical resection Coils to mark M1 if risk of dissapearing Ability to detect missing M1 at the time of surgery varies widely: % Complete pathological or durable clinical response in 26 % - 82 % of patients (mean= 54%) Complete radiological response IS NOT EQUIVALENT to complete pathological response Surgical resection should include all original sites of M1 when feasible When such resections are hazardous, a watch-and-wait strategy can be a reasonable alternative Adams RB et al. Selection for hepatic resection of colorectal liver metastases: expert consensus statement. HBP 2013; 15: Lucidi V et al. Missing metastases as a model to challenge current therapeutic algorithms in colorectal liver metastases. World J Gastroenterol 2016; 22:

24 Simultaneous with primary, sequential bowel-first or liver-first Indications and clinical recommendations Complexity of the colorectal tumor Complexity of liver surgery Comorbidities of the patient-general condition SELECTION Patient fitness Anatomical location: colon, rectum, liver Extent of liver metastases

25 Synchronous primary and liver metastases Summary Multidisciplinary Board Oncological and Surgical strategies Selection of patients for each strategy Planification for an appropriate sequential treatment Simultaneous, bowel-first or liver-first Complex surgical procedures requiring surgical expertise

26

27 Thank you!!

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