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1. Rational for hypothermic perfusion
2. Clarification: In situ - Ex situ
3. Veno-Venous Bypass: yes-no?, never-always?
4. Our experience and lessons learned
Hepatectomy & Hypothermic Perfusion of the Liver
Daniel Azoulay
1. Rational for hypothermic perfusion
1. Rational for hypothermic perfusion
The « central column » of the liver
and the frequent need for total & prolonged
vascular exclusion of the liver
1. Rational for hypothermic perfusion
Azoulay D, et al., HPB in Press
Belghiti J, et al., Ann Surg 1996
1. Rational for hypothermic perfusion
Total Vascular Exclusion
- Hemodynamical Intolerance 10-20%
- Splanchnic congestion
- Continuous and subsequently Time Limited
-« Consensual » Limit = 60 minutes
Limits of Standard TVE
1. Rational for hypothermic perfusion
Vascular Exclusion
with Venous Bypass
Solves the problems of
- hemodynamical intolerance
- splanchnic congestion
But continuous
= remains time limited
Limits of Standard TVE
Metabolic needs: 2.0-fold decrease for every 10°C decline
in tissue temperature.
Techniques & Technologies of LT.
Kato, et al., Am J Physiol Gastrointest Liver Physiol 2002
+
LR under hypothermic perfusion of the liver.
=
In Situ : Portal triade untouched
… no need for reconstruction
Ex Situ : Portal triade
divised and… needs reconstruction
Clarification In situ - Ex situ : variations on a theme
HYPOTHERMIC PERFUSION
Always in Vivo…
Delriviere, Hannoun, J Am Coll Surg. 1995 In Situ - Ante situm
Resection
Clarification: In situ - Ex situ
Belghiti J. et al., Gastroenterol Clin Biol 1991.
In Situ - Ante situm
Clarification: In situ - Ex situ
Mettre livre
Approach to the supra-hepatic IVC: value of ante situm
Ante situm
provides the surgeon
1) Optimal visualization of the hepatic venous confluence
2) A complete resection of the tumor
without transecting the portal triade.
Total 166 TVE: 66% R0: 87% 11/148: 7.4%
61/148: 41%
Tube: 43%
Relevant Reported Series of Combined Liver and IVC Resections Guerrini, Intern J Surg 2015
Hypothermic perfusion
- portal route
- UW solution
Liver Resection with TVE and Hypothermic Perfusion
of the Liver and Veno-Venous Bypass
Preliminary Experience 20 cases
Bypass
UW
4°C
Our experience and lessons learned: Preliminary experience
Azoulay, et al., Ann Surg 2005
• 1- Total vascular exclusion of the liver > 60 minutes is better
tolerated when performed under hypothermic perfusion
• 2- Mortality tends to be lower and morbidity is significatively
lowered following TVE under hypothermic perfusion
compared to standard TVE
• 3- The need for portal vein embolization, the maximum
diameter of the lesion, and a planned vascular reconstruction
are independent predictors of TVE > 60 minutes
Patients and methods
TVE and Hypothermic Perfusion of the Liver: Further experience
1998 - 2010
2455 Hepatectomies
Vascular Exclusion
391 (15.9%)
No Vascular Exclusion
2064 (84.1%)
Vascular Exclusion
Without Caval Clamping
227 (9.2%)
Vascular Exclusion
With Caval Clamping
164 (6.7%)
Hypothermic Perfusion
77 (3.1%)
Without Hypothermic Perfusion
87 (3.6%)
Bypass
UW
4°C
Disease
Colo-rectal metastases
Mass forming cholangiocarcinoma
Hepatocellular carcinoma
Klatskin
Benign Tumor
Other
TVE with
Hypothermia
77 cases
31 (40.2%)
22 (26.6%)
10 (13%)
2 (2.6%)
5 (6.5%)
7 (11%)s
Patients and methods
Bypass
UW
4°C
TVE and Hypothermic Perfusion of the Liver: Further experience
« Biological tolerance »
Azoulay D, et al., Ann Surg 2014
Azoulay D, et al., Ann Surg 2014
Azoulay D, et al., Ann Surg 2014
Three independent predictors of 90-Day mortality
• CCI 3 or more
• Maximum tumor size >10 cm
• Presence of 50/50 criteria
 Expected
 Not controlable
 Too late…
So What?
Azoulay D, et al., Ann Surg 2014
CRLMets, n = 33/36 available
Updated survivals 94 cases (unpublished)
HCC, n = 15
Updated survivals 94 cases (unpublished)
IHCC, n = 26
Updated survivals 94 cases (unpublished)
Veno Venous Bypass
CHB Experience: ⌁Zero severe problem / hundreds of VVBs
Navez et al., HPB in press
VVB Yes
n = 13
96
600
3 (23%)
30%
0
15%
16
VVB No
n = 14
75
1750
2 (14%)
50%
29%
64%
19
Variable
Duration Vasc Exclusion, min
Blood Loss, mL
Mortality
Severe morbidity
Ascites
Resp. complications
Hospital stay, days
p value
0.18
0.01
0.6
0.4
0.04
0.01
0.35
12
14
16
18
20
22
24
26
28
PAP
mm Hg
4.5
5
5.5
6
6.5
7
7.5
8
CO
L/min
4
5
6
7
8
9
10
RAP
mm Hg
NS
NS
NS NS
NS
NS
7.25
7.3
7.35
7.4
7.45
7.5
Arterial
blood pH
34
35
36
37
Central
Temperature
°C
S
S
NS
S
70
75
80
85
90
95
100
105
NS S
MAP
mm Hg
before
during
after before after
during
Liver resection under total vascular exclusion
Veno-Venous Bypass = Hemodynamical stability
Reminder: hemodyn intolerance = 17% in Belghiti et al., Ann Surg 1996
Azoulay D, et al., Liver Transpl 2019
Obviates cumbersome portal canula
Azoulay D, et al., Int Care Med 2019
Azoulay D, et al., HBSN 2014
Personal experience = 8 cases
Ex situ = Portal triade reconstruction needed
Ex Situ Resection
Oldhafer KJ, et al., Surgery 2000
Pichlmayr R, et al., Br J Surg 1990
Nagino, et al., Ann Surg 2010
50 cases of Klatskin tumors 1997 - 2009
Biliary drainage 45 cases (90%)
VVB = ZERO, Hypothermic perfusion = ZERO
Operative mortality = 1 case (2%)
Operative Morbidity = 54 % (27 patients)
« In earlier studies from Pichlmayr et al. …
morbidity and mortality rates were close to 30%.
In the past 15 years, we were able to reduce this
mortality rate to 12.5% in favor of the ante situm
liver resection... »
Oldhafer, et al., Langenbeck’s Arch Surg 2018
Zawistowski zt al., Surgery 2021 in press
Govil al., Indian J Gastroenterol 2013
Balmas-Geaorge al., Langenbeck’Arch Surg 2021
Balmas-Geaorge al., Langenbeck’Arch Surg 2020
In situ vs. Ex situ ? Review (personal)
vs.
vs
Hypothermic perf for malignancy
Postoperative Mortality
12.7% 27.7%
Including
8 cases salvage transplantation…
vs.
13% 20%
Including
8 cases of salvage transplantation…
Left PV invaded
Left branch HA free
Biliary dilatation
PV
LPV
RPV
PV
LPV
RPV
IVC replaced/PTFE graft
PV reconstruction
Biliary drain
S3
S2
LT
LR
LT
LR
LT LT
LR
LR
LR
LR
Oslo Low & High Tumor Burden:
« Selected CRLM with low Oslo Score
and high Tumor Burden Score
could benefit from LT with survival outcomes
that are far better
than what is achieved by LR. »
Lanari J, et al., Transplant Intern 2021
In Situ Hepatectomy & Hypothermic Perfusion of the Liver
Conclusions (1)
• Rare = 3% of highly specialized activity
• Planification/ Adaptation ->bypass, cell saver,
hypothermic perfusate available
• In situ « better » than Ex situ in terms of mortality
Conclusions (2)
• How to improve strategy?
• Improve patient-doctor decision process for this
type of surgery: difficult in the current era of mini-
invasive approach & ERAS…?
• Define the place of salvage liver transplantation ?
In Situ Hepatectomy & Hypothermic Perfusion of the Liver

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Chirurgie hépatique sous perfusion hypothermique - D. Azoulay

  • 1. 1. Rational for hypothermic perfusion 2. Clarification: In situ - Ex situ 3. Veno-Venous Bypass: yes-no?, never-always? 4. Our experience and lessons learned Hepatectomy & Hypothermic Perfusion of the Liver Daniel Azoulay
  • 2. 1. Rational for hypothermic perfusion
  • 3. 1. Rational for hypothermic perfusion
  • 4.
  • 5. The « central column » of the liver and the frequent need for total & prolonged vascular exclusion of the liver 1. Rational for hypothermic perfusion Azoulay D, et al., HPB in Press
  • 6. Belghiti J, et al., Ann Surg 1996 1. Rational for hypothermic perfusion
  • 7. Total Vascular Exclusion - Hemodynamical Intolerance 10-20% - Splanchnic congestion - Continuous and subsequently Time Limited -« Consensual » Limit = 60 minutes Limits of Standard TVE 1. Rational for hypothermic perfusion
  • 8. Vascular Exclusion with Venous Bypass Solves the problems of - hemodynamical intolerance - splanchnic congestion But continuous = remains time limited Limits of Standard TVE
  • 9. Metabolic needs: 2.0-fold decrease for every 10°C decline in tissue temperature. Techniques & Technologies of LT. Kato, et al., Am J Physiol Gastrointest Liver Physiol 2002 + LR under hypothermic perfusion of the liver. =
  • 10. In Situ : Portal triade untouched … no need for reconstruction Ex Situ : Portal triade divised and… needs reconstruction Clarification In situ - Ex situ : variations on a theme HYPOTHERMIC PERFUSION Always in Vivo…
  • 11. Delriviere, Hannoun, J Am Coll Surg. 1995 In Situ - Ante situm Resection Clarification: In situ - Ex situ
  • 12. Belghiti J. et al., Gastroenterol Clin Biol 1991. In Situ - Ante situm Clarification: In situ - Ex situ
  • 13. Mettre livre Approach to the supra-hepatic IVC: value of ante situm
  • 14. Ante situm provides the surgeon 1) Optimal visualization of the hepatic venous confluence 2) A complete resection of the tumor without transecting the portal triade.
  • 15. Total 166 TVE: 66% R0: 87% 11/148: 7.4% 61/148: 41% Tube: 43% Relevant Reported Series of Combined Liver and IVC Resections Guerrini, Intern J Surg 2015
  • 16. Hypothermic perfusion - portal route - UW solution Liver Resection with TVE and Hypothermic Perfusion of the Liver and Veno-Venous Bypass Preliminary Experience 20 cases Bypass UW 4°C Our experience and lessons learned: Preliminary experience
  • 17. Azoulay, et al., Ann Surg 2005 • 1- Total vascular exclusion of the liver > 60 minutes is better tolerated when performed under hypothermic perfusion • 2- Mortality tends to be lower and morbidity is significatively lowered following TVE under hypothermic perfusion compared to standard TVE • 3- The need for portal vein embolization, the maximum diameter of the lesion, and a planned vascular reconstruction are independent predictors of TVE > 60 minutes
  • 18. Patients and methods TVE and Hypothermic Perfusion of the Liver: Further experience 1998 - 2010 2455 Hepatectomies Vascular Exclusion 391 (15.9%) No Vascular Exclusion 2064 (84.1%) Vascular Exclusion Without Caval Clamping 227 (9.2%) Vascular Exclusion With Caval Clamping 164 (6.7%) Hypothermic Perfusion 77 (3.1%) Without Hypothermic Perfusion 87 (3.6%) Bypass UW 4°C
  • 19. Disease Colo-rectal metastases Mass forming cholangiocarcinoma Hepatocellular carcinoma Klatskin Benign Tumor Other TVE with Hypothermia 77 cases 31 (40.2%) 22 (26.6%) 10 (13%) 2 (2.6%) 5 (6.5%) 7 (11%)s Patients and methods Bypass UW 4°C TVE and Hypothermic Perfusion of the Liver: Further experience
  • 20. « Biological tolerance » Azoulay D, et al., Ann Surg 2014
  • 21. Azoulay D, et al., Ann Surg 2014
  • 22. Azoulay D, et al., Ann Surg 2014
  • 23. Three independent predictors of 90-Day mortality • CCI 3 or more • Maximum tumor size >10 cm • Presence of 50/50 criteria  Expected  Not controlable  Too late… So What? Azoulay D, et al., Ann Surg 2014
  • 24. CRLMets, n = 33/36 available Updated survivals 94 cases (unpublished)
  • 25. HCC, n = 15 Updated survivals 94 cases (unpublished)
  • 26. IHCC, n = 26 Updated survivals 94 cases (unpublished)
  • 27. Veno Venous Bypass CHB Experience: ⌁Zero severe problem / hundreds of VVBs Navez et al., HPB in press VVB Yes n = 13 96 600 3 (23%) 30% 0 15% 16 VVB No n = 14 75 1750 2 (14%) 50% 29% 64% 19 Variable Duration Vasc Exclusion, min Blood Loss, mL Mortality Severe morbidity Ascites Resp. complications Hospital stay, days p value 0.18 0.01 0.6 0.4 0.04 0.01 0.35
  • 28. 12 14 16 18 20 22 24 26 28 PAP mm Hg 4.5 5 5.5 6 6.5 7 7.5 8 CO L/min 4 5 6 7 8 9 10 RAP mm Hg NS NS NS NS NS NS 7.25 7.3 7.35 7.4 7.45 7.5 Arterial blood pH 34 35 36 37 Central Temperature °C S S NS S 70 75 80 85 90 95 100 105 NS S MAP mm Hg before during after before after during Liver resection under total vascular exclusion Veno-Venous Bypass = Hemodynamical stability Reminder: hemodyn intolerance = 17% in Belghiti et al., Ann Surg 1996
  • 29. Azoulay D, et al., Liver Transpl 2019 Obviates cumbersome portal canula
  • 30. Azoulay D, et al., Int Care Med 2019
  • 31. Azoulay D, et al., HBSN 2014 Personal experience = 8 cases
  • 32. Ex situ = Portal triade reconstruction needed Ex Situ Resection Oldhafer KJ, et al., Surgery 2000 Pichlmayr R, et al., Br J Surg 1990
  • 33. Nagino, et al., Ann Surg 2010 50 cases of Klatskin tumors 1997 - 2009 Biliary drainage 45 cases (90%) VVB = ZERO, Hypothermic perfusion = ZERO Operative mortality = 1 case (2%) Operative Morbidity = 54 % (27 patients)
  • 34. « In earlier studies from Pichlmayr et al. … morbidity and mortality rates were close to 30%. In the past 15 years, we were able to reduce this mortality rate to 12.5% in favor of the ante situm liver resection... » Oldhafer, et al., Langenbeck’s Arch Surg 2018
  • 35. Zawistowski zt al., Surgery 2021 in press Govil al., Indian J Gastroenterol 2013 Balmas-Geaorge al., Langenbeck’Arch Surg 2021 Balmas-Geaorge al., Langenbeck’Arch Surg 2020
  • 36. In situ vs. Ex situ ? Review (personal) vs. vs Hypothermic perf for malignancy Postoperative Mortality 12.7% 27.7% Including 8 cases salvage transplantation… vs. 13% 20% Including 8 cases of salvage transplantation…
  • 37. Left PV invaded Left branch HA free Biliary dilatation
  • 40. IVC replaced/PTFE graft PV reconstruction Biliary drain S3 S2
  • 41. LT LR LT LR LT LT LR LR LR LR Oslo Low & High Tumor Burden: « Selected CRLM with low Oslo Score and high Tumor Burden Score could benefit from LT with survival outcomes that are far better than what is achieved by LR. » Lanari J, et al., Transplant Intern 2021
  • 42. In Situ Hepatectomy & Hypothermic Perfusion of the Liver Conclusions (1) • Rare = 3% of highly specialized activity • Planification/ Adaptation ->bypass, cell saver, hypothermic perfusate available • In situ « better » than Ex situ in terms of mortality
  • 43. Conclusions (2) • How to improve strategy? • Improve patient-doctor decision process for this type of surgery: difficult in the current era of mini- invasive approach & ERAS…? • Define the place of salvage liver transplantation ? In Situ Hepatectomy & Hypothermic Perfusion of the Liver