Management of Liver

Metastasis from
Colorectal Cancer

Wifanto S Jeo – Ibrahim Basir

Digestive Surgery
Jakarta 2017
 Scope of View

• Colorectal Cancer Liver Metastasis

(CRCLM)
• Hepatectomy in CRC
• Increasing Resectability
• Synchronous Liver Metastasis
 Colorectal Cancer
Liver Metastasis
• Basic Facts & Figures:
– 2nd & 3rd most common cancers in males
and females.
– 9% of cancer related deaths.
– Over All Survival (OAS) for entire patients
65%.
• At diagnosis : 25% CRC with synchronous
hepatic metastasis
• Metastatic disease: 5-year OAS 10%.
• Median survival of metastatic disease > 24 -
30 months with efective chemotheraphy
Kopetz et al, 2009
CRC in Indonesia
GLOBOCAN 2002, IARC. United States Census Bureau
 Sites of Colorectal
Metastasis
• Peritoneum
• Liver
• Lung
• Ovary
• Bone
• Brain
• Incisions
• Spleen
• Other means a potential cure
 Survival in CRC

Stage 0 month 30 m 60 m
% Survival % Survival % Survival
I 100 96.1 93.2
IIa 100 91.0 84.7
IIb 100 80.2 72.2
IIIa 100 91.4 83.4
IIIb 100 77.3 64.1
IIIc 100 67.1 52.3
IIId 100 57.3 43.0
IIIe 100 43.1 26.8
IV 100 17.3 8.1

O’ConnellJB, Maggard MA, Ko CY: Colon Cancer Survival Rates with The New American Joint
Committee on Cancer, Sixth Edition Staging. J Natl Cancer Inst 2004;96:1423.
Colorectal Cancer Mortality
 Advances Treatment of
Stage IV CRC
1980 1985 1990 1995 2000 2005 2010 2015

BSC
35 5-
FU Irinotecan
30
Capecitabine
25 Oxaliplatin
OS (monthas)

20 Cetuximab
Bevacizumab
15 Panitumumab
10 Aflibercept
Regorafenib
5 median overall BBP
survival
0
198 1985 1990 1995 2000 2005 2010 2015
0
 Results of Hepatic Resection for
Patients with mCRC
Survival (%)
Author (year) No.Pt Mortality Median Survival 1-year 5-year
Hughes et al 607 --- --- --- 33
(86)
Gayowski et al 204 0 33 mo 91 32
(94)
Scheele et al 469 4 40 mo 83 39
(95)
Fong et al (95) 577 4 40 mo 85 35
Jamison et al 280 4 33 mo 84 27
(97)
Fong et al (99) 1001 3 42 mo --- 36

Choti et al (02) 226 1 46 mo 96 40

Pawlik et al (05) 557 1 74 mo 97 58

 Colorectal Cancer
Hospital Based Jakarta 2010-2015
Criteria Numbers %
Sex Male 378 55
Female 310 45
Staging I 23 3.3
II 141 20.5
III 337 48.9
IV 167 24.3
Location Rectum 423 61.5
Liver Resection mCRC No Notes
Colon 265 38.5
Metasectomy 6 Segment 2,5,6,8
Left Lateral 2 Segment 2-3 RSCM
Sectionectomy Digestive Division
Total 8 4.8% from Stage IV
 Preoperative Evaluation
• Medical fitness for surgery
• Detemination of Oncologic and Technical Resectability
• High quality preoperative imaging
– Ultrasonography (US) : number, size and anatomic
relationships
– CT Scan : precontrast, arterial, delayed or venous
phases
Coronal and sagital reconstructions
Three dimensional reconstructions : future liver
remnant volume
– MRI
– PET Scan
 CT Scan 3 Phases
Radiologist Assestment

CT Scan Non Arterial Venous Delayed

3 Phases contras Phase Phase Phase
(30”) (60”) (3-10’)
Liver Metastasis Solid/multi Hipodens>> Wash out Wash out
ple > /hiperdens

HCC Solid En En/wash out Wash out

central/perif
er
Cholangiocarcinoma Solid En perifer En/wash out En
central

Liver Abscess Cyst En perifer Wash out Wash out

En= Enhancement
 Hepatectomy in mCRC
40

• Mortality : 5% or less 35

• Morbidity : 20-50% 30

• 5-year survival : 25- 25 mCRC

40% 20
• 10-year survival :20- mCRC
15 Hepatect
26% omy
10
• Median survival 24-46
months 5

0
5Years 10Years
Management of mCRC

JNCCN 2017
 Traditional Definition of
Resectability
• Metachronous detection
• Unilobar disease
• <4 metastases
• <5 cm largest metastasis
• >1 cm resection margin

Rees et al 1997
Technically “Unresectable”
1.Direct invasion into
hepatic/portal
veins
2.Multicentric tumors
or satellite nodules
3.Proximity to major
vascular structures
4.Severe cirrhosis
with lacking
functional hepatic
reserve
 Resectable vs Unresectable
Lesion
Resectable Lesion Parenchymal obliteration

19
 Resectable vs Unresectable
Lesion
Resectable or Unresectable Lesion?

20
 Change in Paradigm

“Can all disease be resected while

leaving
a functional liver remnant?”

What is
What is left
resected

21
New Definition of Resectability
 Factors considered
Important Evaluation
• Medical fitness (Tolerate to surgery)
• Child-Pugh score
• Adequate functional liver after
surgery
• Adequate portal flow
• Adequate hepatic venous out-flow
• Adequate biliary drainage
Child-Pugh Score
 Resectability

• Solitary, multiple, or bilobar disease who have

had curative intent treatment of their primary
tumors are candidates for liver resection
• Focuses on achieving an R0 resection, including
resection of limited extrahepatic disease
• If necessary, this is achieved in combination with
other methods
 Future liver remnant volume

• At least 20% of the total liver volume (TLV) in

patients with a healthy liver, in the absence of
unresectable extrahepatic disease
• Patients that have been submitted to many
chemotherapy cycles need at least 30%
• Patients with chronic hepatopathy one can
estimate 40%

20% 30% 40%

 Criteria of Resectability
• Three category :
– Clearly Resectable
– Unresectable but potentially covertible
– Unresectable unlikely become resectable
• French Recommendations :
– Class I : Easily resectable
• Four or less than 4 segments involved and residual
healthy liver volume > 40%
• Vena cava free from tumor
• One or less involvement of hepatic vein
 Criteria of Resectability
• French Recommendations :
– Class II : Potentially resectable
• Five to six segments involved
• + contralateral major named vascular structure
within liver
• Need complex and large resection
– Unresectable
• Involvement of two portal branches
• Involvement of one portal branch and a
contralateral hepatic vein
• Involvement of three hepatic vein
Systemic Treatment
Recommendation

Ismaili et al, WJSO 2011

 Strategies to Increase
Resectability
• Conversion Therapy - transforming an initially
unresectable disease into a resectable one using
Chemotherapy and/or Targeted therapy
• Portal Vein Embolization
• Two-Stage Hepatectomy
• Special Techniques : ALPPS

Coimbra et al. Rev Assoc Med Bras 2011; 57(2)

Increase Resectability :
Conversion Therapy
 Increase Resectability :
Conversion Therapy
• Neoadjuvant chemotherapy
– Increasing percentage of resectability
– Achieving a limited hepatectomy
– Treatment of micro-metastasis
– Evaluation of chemosensitivity of the disease
• Liver injury related to neoadjuvant chemotherapy
– Steatosis and steatohepatitis
– Vascular damage or sinusoidal obstruction syndrome :
portal hypertention, asites, hyperbilirubinemia
– Drug specific toxicity
• Interval to surgery : 6-8 weeks
Increase Resectability :
Portal Vein Embolization
 Increase Resectability :
Portal Vein Embolization
• Absolute contraindication :
– Establish Portal hypertension
– Extensive tumor trombus of ipsilateral portal vein
• Access route : transileocolic, percutaneus
transhepatic ipsilateral or contralateral

Aoki T et al, World J Hepatol. 2016;8(9):439-455

 Two-Stage Hepatectomy

Concept

• Two sequential liver resections aiming to

resect multinodular hepatic tumors

irresectable by a single procedure

- Regeneration following hepatectomy

- Planned strategy at the time of 1st
hepatectomy
Adam R, et al. Ann Surg 2000; 232:777-85
Two-Stage Hepatectomy
Two-Stage Hepatectomy 155 cc

1I

440 cc
IV
I
2

(1) Adam R, et al. Ann Surg 2000; 232:777-85

 Special Technique in Liver
Resection
• ALPPS = Associating Liver Partition and Portal vein
Ligation for Stage Hepatectomy
• First report by Schnitzbauer et al. (Germany) 2012 and
followed by many liver surgeons

Schnitzbauer et al, Ann Surg 2012;255:405-414

Special Technique in Liver
Resection

Schnitzbauer et al, Ann Surg 2012;255:405-414

Special Technique in Liver
Resection
• 76yo male with
multiple
synchronous CRCLM

Jiao et al, Hep 2012;255:405-414

 Male, 57yo, Liver metastasis Sigmoid
Adenocarcinoma

Targeted Chemotherapy Metasectomy Segment 8

41
Male, 60yo, Liver Metastasis
Rectal Adenocarcinoma

42
Simultaneous Sigmoid Resection and
Left Lateral Segmentectomy

Female 49 yo
 Synchronous Liver Metastasis

• By avoiding a second laparotomy, simultaneous

colon and hepatic resection reduces overall
hospital stay, no difference in morbidity and
mortality rates compared with staged resection
• Simultaneous resection is an acceptable option in
patients with resectable synchronous colorectal
metastasis
 Synchronous Liver Metastasis

Classic or Simultaneous Liver First

• Classic approach • Advances in surgical

• Symptomatic mCRC techniques
– Bleeding • Advances in surgery
– Obstruction equipment and
• Combine with resection instrument
liver metastasis • Following Targeted or
• Less than 3 segment chemotheraphy
resection (minor • Limitted progression
resection) time to unresectable
• Require major hepatic
resection
mCRC with LLD: Key Players
Systemic Cures 2 –
Therapies 10%
Alone of Patients

Cures >
Surgery
30%
Alone
of Patients

Don’t Miss Surgical Intervention

The Race Toward More Responses

and Survival
 Take Home Message

• CRC is among disease associated with

reduction of mortality over the past decade.
• Surgical resection undoubtedly remains the
gold standard for the treatment of CRC as
well as resectable liver metastases
• Paradigm in liver resection and techniques
increasing resectability have challenge in
mCRC management.
• Multimodality treatment in CRCLM will
increase more responses and survival.