Talk about liver surgery

1. Treatment of Liver Tumours-
Current Trends
Dr.Venugopal B
Dept .of HPB & Liver Transplant
KIMS, Thiruvananthapuram.

2. Liver Tumours
• Benign
• Malignant
-Primary
Hepatocellular ca
Cholangio Ca
-Secondary
Colorectal
Neuroendocrine
Non colorectal non neuroendocrine

3. Hepatocellular carcinoma
• 5th most common malignancy
• 3rd most common cause of cancer death
• 70% occur in Cirrhotic livers
• Incidence is increasing

4. Treatment options
• Surgical resection
• Liver transplantation
• Radiofrequency ablation
• TACE, TARE
• Radiotherapy
• Targeted therapy

5. Treatment selection
• Applicability
• Safety
• Efficacy

6. BCLC staging

7. Surgical resection
• Cirrhotics with HCC (<5%)
• HCC without cirrhosis
• Criteria
-Child-Pugh class A
-Normal bilirubin
-Absence of portal hypertension
- <5cm in diameter

8. Postoperative Liver Failure is the commonest
cause of mortality

9. Risk factors for Liver Resection
• Advanced age
• Comorbidities
• Chronic Liver Disease
• Cholestatic liver
• Post chemotherapy liver
• Extent and complexity of the resection

10. Cause of Postoperative Liver Failure
• Impaired functional reserve
• Inadequate residual volume

11. Risk assessment
• Clinical
• Biochemical
• Volumetric
• Functional

12. Portal hypertension
• Previous variceal haemorrhage or ascites
• Presence of oesophageal varices
• Platelet count <100000
• Radiologically visible portosystemic shunt

13. Indocyanine green clearance test
< 14% 14-20%
>20%
Major hepatic resection
contraindicated
&
Adequate liver remnant CT
Major hepatectomy

14. Child- Pugh score
• Child A - major liver resection
• Child B - segmental/subsegmental
resection
• Child C - Absolute contraindication

15. Contrast CT scan
• Site , Size
• Relation to blood vessels
• Residual liver volume(FLRV)

16. TUMOR VOLUME

18. Safe remnant liver volume
Residual liver volume
• FLRV = Total liver volume - Tumor volume
• >30% - Normal liver
• > 40% - Cirrhotic

21. Strategies to deal with impaired
functional reserve
• Parenchyma sparing resection
• Resection after PVE
• Resection in combination with RFA
• Two stage resection
• Resection after chemotherapy
• Resection after TACE

22. Augmentation FLRV
• PVE
• PV ligation
• Repeat CT after 3 weeks
• FLRV increases by 20-46%
• Resectability 70 to 100 %
• Can be used as a dynamic test for liver
regeneration

23. not randomized but alternatively assigned
28 pts with PVE
27 pts without PVE
Portal Vein Embolization Before Right
Hepatectomy
Farges O, Belghiti J et al, Ann Surg 2003;237:208-17
future liver remnant volume after PVE
4419% in normal liver
3528% in chronic liver disease
the postoperative course and
complications
 similar between PVE(+) and (-) in
normal liver
 significantly decreased in PVE(+) with
chronic liver diseases, but no difference in
surgical mortality

24. Portal vein embolisation

25. Portal vein embolisation

27. Safe Liver
Resection
Adequate
Biliary
drainage
Adequate
functioning
Parenchyma
Adequate
outflow
Adequate
Inflow

31. Surgical resection -Result
• 5 yr survival: 60-70%
• Tumour recurrence: 50% at 3 yrs

32. Liver transplantation for HCC
• Ideal treatment for small HCC in Cirrhotics
-Widest possible surgical margin!
-Cure of underlying liver disease
(denovo tumorogenesis)

33. Early Results
Survival(%) Recurrence (%)
Center 1 yr 2 yr 3 yr
Cincinnati 45 30 20 39
UCLA 40 22 – 67
Cambridge 45 38 – 65
Pittsburgh 64 47 48 43
Liver Transplantation for
Hepatocellular Carcinoma

34. Liver Transplantation for HCC
• Early experience in 1980s- disappointing
• Paul Brousse > 50% DFS 3yrs
Single <3cm, < 3tumour
Bismuth etal. Ann Surg 1993
• Milan group 4yr OS 75% DFS 83%
Single <5cm, <3 tumours <3cm
Mazaffero etal. NEJM 1996

35. UCSF Criteria
• Lesion <6.5cm
• 2-3 lesions
-Largest <4.5cm
-total dia <8cm
• No vascular invasion
• No extrahepatic metastases
• One yr survival 90%
• Five yr survival 75%
Yao FY etal.Hepatology2001;33: 1394-403

38. Radiofrequency Ablation
• Local application of thermal energy generated
by high frequency electric current
• Complete ablation in tumours up to 4cm

39. Radiofrequency Ablation

40. • 148 pts, single, small (< 4cm)
• RFA: 55 pts, Resection: 93 pts
• Recurrence:
RFA: 58.2%---- 40% remote, 18.2% local
Resection: 45.2%---- 43% remote, 2.2% local
• Survival:
RFA: 100%, 72.7% at 1 & 3 yrs
Resection: 97.9%, 83.9% at 1 & 3 yrs
SN Hong et al. J Clin Gastroenterol 2005;39:247 Samsung Medical Center, Seoul, Korea
Hepatocellular Carcinoma
Resection vs RFA

41. BEFORE RF AFTER RF

42. Resection vs RF ablation
• Similar results for tumours < 3cm
• Comparable for 3 to 5 cm
• Resection better for >5cm

43. Transarterial chemoembolisation-
Contrindications
• Serum bilirubin >2mg/dl
• LDH >425 U/L
• AST >100 U/L
• Tumour burden >50% of the Liver
• Cardiac or renal insufficiency
• Ascites,recent variceal bleed or significant
thrombocytopenia

44. Transarterial Chemoembolization
Meta-analysis of 7 randomized controlled trials
• 2 yr survival: 41% (19-63%)
• Treatment response: 35% (16-61%)
• Average no. of sessions: 1-4.5
• Risks:
– Infection
– Tumor lysis syndrome
– Hepatic failure
• Llovel J He aloI2003"37:429

45. Radioembolization
• Similar to TACE
• Use radiation particles eg Yttrium, Rhenium
• Results slightly better than TACE

46. Targeted therapy
• Sorafenib
-increases survival
-Disease progression delayed

47. Colorectal Liver Metastases

48. Introduction
Liver is the most common site for hematogenous metastasis
from colorectal carcinomas.
~ 25% synchronous.
Bengmark S. Cancer 23: 198- 202
~ 50% metachronous
Bozzetti F. Ann Surg 205:264- 270
In patients with isolated liver metastasis, the extent of liver
disease is the prime determinant of survival.

49. Natural History of CRM
Stangl R et al –Lancet 1994
Prospective study 1980-1990
484 consecutive untreated patients
Avg survival(yr) 31%-1 ,7.9%-2, 2.6%-3,
0.9%-4 (Median survival 7.5 months)
The prosnosis is most closely related to the extent of liver
replacement by tumor.

50. Natural History of CRM
• Wagner JS Ann Surg 1984
Study comparing outcome in potentially
operable but not resected metastases with
those who underwent surgery
5- year survival 25% in the operated group
compared to 2%in the nonoperated group.

51. Colorectal liver met-treatment options
• Resection
• Ablation
• Liver directed therapy
• Chemotherapy

52. Rationale for treatment
• Spread to liver is via portal circulation before
systemic spread.
• Stepwise spread provides an opportunity to prevent
dissemination of tumor to other sites by treatment
of hepatic metastasis.
• This way hepatic colorectal metastasis differ from
other metastasis.
• Regenerative capacity of liver has allowed major
resections to be possible with increasing frequency

53. • Hepatic resection has become standard treatment
after Foster et al showed survival after hepatic
resection to be consistently above 20% as compared
to 0% with no treatment.
• With improvement in surgery, resection of hepatic
metastatic tumors have been increasingly
undertaken
• 5 year survival after margin negative hepatic
resection have been 24-58%(40%) with 10 year
survival of 15-20%.

54. Prognostic scoring
• Fong et al Ann Surg 1999
Data base of 1001 consecutive patients
undergoing hepatic resection for CR metstases
5 preoperative clinical criteria for clinical risk score
• Disease free survival <12 months
• Number of mets >1
• Preoperative CEA level>200U/ml
• Size of largest lesion >5cm
• Lymphnode positive primary tumor

55. Clinical risk score
• Presence of any one characteristic was
associated with 5 year survival of 24-34%
• Score of 2 or less –good prognosis (ideal for
resection)
• 3-4 outcome less favorable so aggressive trial
of adjuvant therapy required
• 5- long term survivors are rare so adjuvant
treatment trials are required

56. Patient selection -Imaging
• CECT
• MRI
• PET Scan

57. Effect of PET Before Liver Resection on Surgical
Management
for Colorectal Adenocarcinoma Metastases
A Randomized Clinical Trial
Carol-Anne Moulton, MB, BS; Chu-Shu Gu, MSc; Calvin H. Law, MD; Ved R. Tandan, MD; Richard Hart, MD; Douglas
Quan, MD;
Robert J. Fairfull Smith, MB; DiederickW. Jalink, MD; Mohamed Husien, MD; Pablo E. Serrano, MD; Aaron L. Hendler,
MD; Masoom A. Haider, MD;
Leyo Ruo, MD; Karen Y. Gulenchyn, MD; Terri Finch, BA; Jim A. Julian, MMath; Mark N. Levine, MD; Steven
Gallinger,MD
CONCLUSIONS AND RELEVANCE Among patients with potentially
resectable hepatic
metastases of colorectal adenocarcinoma, the use of PET-CT
compared with CT alone did not
result in frequent change in surgical management. These findings
raise questions about the
value of PET-CT scans in this setting.
JAMA. 2014;311(18):1863-1869. doi:10.1001/jama.2014.3740

58. Patient selection –Criteria for
unresectability
• Nontreatable extrahepatic disease
• Unfitness for surgery
• Involvement of >70 % of liver or 6 segments

59. Resectability
• Currently, hepatic colorectal metastases should be defined as
resectable when
– Disease can be completely resected
– 2 adjacent liver segments can be spared
– Adequate vascular inflow and outflow and biliary drainage can be
preserved
– Volume of the liver remaining after resection (i.e., the ‘‘future liver
remnant’’) will be adequate (at least 20% of the total estimated liver
volume).
• Instead of resectability being defined by what is removed,
decisions regarding resectability should now focus on what
will remain following resection.

60. Who cannot be operated

61. Resection for CRLM- Clinical situation
• Synchronous lesions
• Metachronous lesions

62. Timing of resection and synchronous lesion
• Best timing not yet defined
• Most investigators recommend staged
approach 2-3 months after resection of
primary
• Recently few series have shown equal results
with simultaneous resections

63. • Staged or simultaneous resections can be
considered depending on
– Complexity of resections
– Symptoms
– Comorbid disease
– Available surgical expertise

64. Extrahepatic disease
• No longer be considered an absolute C/I to hepatic
resection
– If the patient is carefully selected
– Complete (margin-negative) resection of both intra- and
extrahepatic disease is feasible.
• Survival rate was significantly higher in patients with
– fewer than five liver metastases
– Who received neoadjuvant chemotherapy
– In whom a complete resection could be achieved.

65. Residual liver volume
• 20% of residual liver volume is adequate for
normal liver
• Most paitents with CRM have received
chemotherapy and have CASH
• Exact extent of FRLV has not been defined.
• PVE helps in improving the resectability by
hypertrophy of residual liver and providing
adequate FRLV.

66. Indications of PVE
• FLRV ≤ 20% of TLV in patients with normal
liver
• FLRV ≤ 30% of TLV in patients who have
received extensive chemotherapy;
• FLRV ≤ 40% of TLV in patients with hepatic
fibrosis or cirrhosis.

67. Margin status
• Negative resection margin decreases local recurrence
rates and improves survival
• Cady et al recommended minimum margin of 1 cm
• Multicenter study 0f 557 pts.
• No difference in 5 yr OS or tumour recurrence rate
for tumour free margin of 1-4mm,5-9mm or >10mm
Ann Surg 2005: 241:715

68. Radiological vs Pathological response
• Radiological complete response is rarely
associated with complete pathological
response
• Pathological response only in 4 to 9 %
• Mapping and timing of resection are critical.
• Resection should encompass segments
involved based on pre-chemotherapy imaging.

69. Metachronous mets- Timing of sugery
Upfront Surgery
vs
Upfront Chemotherapy

70. Upfront surgery indications
• Low risk patients
-medically fit
-four or fewer lesions
• Potentially resectable

71. Upfront chemotherapy- Evidence

72. EORTC 40983- Perioperative FOLFOX
vs. Surgery for resectable CRLM
• Eligibility:
• 1-4 Liver metastases that were technically
resectable
• No extrahepatic (non-primary) disease
• No prior oxaliplatin
• Design:
• Experimental arm: 6 cycles (12 weeks) FOLFOX4
pre- and post surgery
Lancet. 2008 Mar 22;371(9617):1007-16

73. EORTC Trial
• Total no 364 Chemo 182 Resection 182
Resection rate 83% vs 84%
Nontherapeutic Lap 8/159(5%) vs 18/170(11%)
Postop complications 25% vs 16 %
Mortality 1 vs 2

74. EORTC Result
• Media follow-up 8.5 yrs
• 5 yr PFS 38% vs 30%( HR 0.81, p= 0.068)
• 5 yr OS 51% vs 48% (HR 0.88, 95% CI 0.68-
1.14)

75. Aggressive surgical approach
• Repeat hepatectomy: 60-70% of operated
cases develop recurrance. One third are liver
only mets.
• Of these 10- 15% candidates for repeat
resection.
• Periop mortality 1- 9%
• Median survival 37 months.
Jarnagin. Ann Surg
• Recurrence rate ~70%

76. Aggressive surgical approach
• En bloc vascular (IVC, hepatic vein) resection
and Ex vivo surgery:
• For liver mets in central and posterior
segments.
• Significant mortality and morbidity (~30%)
• Median survival 19 months.
Miyazaki M. Am j Surg

77. Aggressive Surgical approach

78. Conversion chemotherapy
• Preoperative chemotherapy permits complete
resection in 12-33% of patients who were considered
unresectable
• Survival in these patients is similar to those who have
hepatic resection upfront ( 5yr SR 30 to 35%)
• Chemotherapy regimens based on (5-FU) rarely
provided sufficient intrahepatic tumoricidal effect to
convert hepatic metastases from unresectable to
resectable (response rate < 20%).
• Actual conversion only 5 to 15%

79. Study Phase Regimen Number of
patients
Response rate Resection rate R0 rate
First BEAT IV Chemotherapy+
bevacizumab
1914
704 (liver only)
225 (11.8%)
107 (15.2%)
173 (9.0%)
85 (12.1%)
NO16966 III FOLFOX/XELOX+
bevacizumab
FOLFOX/XELOX+
placebo
699 211 (liver
only)
701 207 (liver
only)
38%
38%
44 (6.3%)
24 (11.6%) 34
(4.9%)
24 (11.6%)
CRYSTAL III FOLFIRI+cetuxi
mab
FOLFIRI
599
599
57.3% (WT)
39.7% (WT)
7%
3.7%
4.8%
1.7%
OPUS II FOLFOX+cetuxi
mab
FOLFOX
169
168
57% (WT)
34% (WT)
4.7%
2.4%
CELIM II FOLFOX+cetuxi
mab
FOLFIRI+cetuxi
mab
56
55
68%
57%
20 (38%)
16 (30%)
Table 2. Conversion rates in unresectable colorectal cancer liver metastases patients treated with bevacizumab or cetuximab containing regimens.
WT, KRAS wild-type.

80. Intra arterial approaches
• Infusion
• Chemoembolization
• Radioembolization (SIRT)

81. • Given the effectiveness of systemic
chemotherapy, regional chemotherapy should
be used in conjunction with systemic
chemotherapy.
• Too little data exist to determine an overall
advantage of one form of regional therapy
over another

82. RFA
• RFA is indicated in unresectable tumors due to
– Size
– Location
– Number of lesions
– Co morbid conditions
• Mainly used as palliative therapy
• Can be used with resection in borderline
resectable tumors

84. Metastatic Liver Tumors – Neuroendocrine
Tumors
• Functional (carcinoid syndrome)
• Non functional

85. Metastatic Liver Tumors – Neuroendocrine
Tumors
Workup
• CT
• MRI
• Octeriotide scan
• Dota PET scan

86. Metastatic Liver Tumors – Neuroendocrine
Tumors
Treatment modalities
• Liver resection and debulking (90%
debulking)
• Ablation
• Liver directed therapy; chemoembolization,
radioembolization
• Chemotherapy or hormonal therapy
• PRRT

87. Metastatic Liver Tumors – Neuroendocrine
Tumors
Hepatic resection
 surgical resection is the first line treatment
Rationale
Slow growing tumor (ineffective to
radiochemotherapy)
Biologically active tumors – mass dependent
hormone production
5 yr survival- 85- 100%

90. Metastatic Liver Tumors – Neuroendocrine
Tumors
Hepatic Transplantation
• Offers potential for cure or best palliation
•Prerequisites – complete excision of primary
& regional disease
• 5 yr survival- 36- 89%

91. Metastatic Liver Tumors – Neuroendocrine
Tumors
Hepatic Transplantation
•Factors increasing survival (Fernandez
2003)
– Age less than 50 years
–Limited hepatic metastases
– low Ki67 index
– regular E-cadherin staining
– R0 resection of the primary NET with no

92. Non colorectal Non neuroendocrine Metastasis
(NCNN)
• Role of hepatectomy in (NCNN) tumors not
well defined
• Increasing publications
• Overall 5 yr survival: 25- 36%
• Tumors of various pathological types resected
– Influences the outcome

93. Non colorectal Non neuroendocrine Metastasis
(NCNN)
MSKCC series from 1981- 2002
Tumor pathology %age
Breast 20
Melanoma 12
Reproductive tract 28
Testicular 14
Gynecologic (ovarian, endometrial, cervical) 14
Adrenocortical 11
Renal 8
Gastrointestinal ( stomach, duodenum, periampullary, anal) 9
Others (lung, salivary gland, nasophyrangeal, thyroid, tonsil, sweat
gland)
9
Unknown 3

94. Non colorectal Non neuroendocrine Metastasis
(NCNN)
MSKCC series from 1981- 2002
Tumor pathology %age
Breast 20
Melanoma 12
Reproductive tract 28
Testicular 14
Gynecologic (ovarian, endometrial, cervical) 14
Adrenocortical 11
Renal 8
Gastrointestinal ( stomach, duodenum, periampullary, anal) 9
Others (lung, salivary gland, nasophyrangeal, thyroid, tonsil, sweat
gland)
9
Unknown 3
Median follow-up: 35 months
30 day mortality- 0 %
3-year relapse-free survival rate was 30%
3-year cancer-specific survival rate was 57%

95. Liver Metastases: Gastric GIST with liver
mets
• Most common indication among sarcomas
• Imatinib changed natural history of the
disease
• 5-year overall survival rate: 30% in resected
patients versus only 4% who do not
underwent resection
MSKCC data

98. Thank you