Critical care aspects of GI surgery by Professor Lars Lundell

2. Esophagectomy

3. postoperative morbidity
30-50%

4. 4
Can we make the train smaller?
21/01/2018Name Surname

5. Transthoracic vs transhiatal esophagectomy

6. AXON05/NK/6/UEGW
Variable
•
•Hospital stay 15 (8-53) 19 (7-154) p<0,01
•Mortality 0
•Resp. compl. p<0,01
•Anast. leakage 6 6
•
• p<0,01
Variable THO (n=106) TTO (n=114)
•ICU stay (days) 2 (0-21) 6 (0-71) p<0,01
•Hospital stay 15 (8-53) 19 (7-154) p<0,01
•Mortality 2(2%) 5(4%)
•Resp. compl. 29 (27%) 65 (57%) p<0,01
•Anast. leakage 6 10
•Vocal cord palsy14 (13%) 24(21%)
•no lymph nodes16 +/-9 p<0,001
Transhiatal (THO) vs Transthoracic (TTO) Oesophagectomy
(Hulscher et al 2002)
31 +/-14

9. 0 20 40 60 80
pulmonary infection (%)
Hospital stay (days)
SF 36 (physical)
QLQ C30
MIE
Open TA
Minimal invasive vs open esophagectomy for esophageal cancer
Biere et al 2012

10. 0 10 20
% pneumonia
% resp. insuff
% ARDS
post op hopital stay
(days)
Open
HMIO
Hybrid Minimal Invasive compared to Open Esophagectomy
Briez et al 2012

11. Transition from open to minimally invasive esophagectomy from 2011 to 2016.
Rouvelas et al 2017

12. Preoperative risk assessment and prevention in esophageal cancer surgery
Grotenhuis
et al 2010

13. Still competitive
Preoperative risk assessment and prevention (?) in esophageal cancer surgery

14. Radiation
exposure and
damage to
surrounding
organs

15. Echocardiographic findings
14/10/2015 Name Surname 15
Lund et al 2015

16. Chemotherapy Chemoradiotherapy
Variable Pre neoadjuvant Post neoadjuvant Pa Pre neoadjuvant
Post
neoadjuvant pa pb
EF (%) 59 (56–62) 57 (53–60) >0.99 60 (57–64) 59 (55–63) >0.99 0.80
GS (%) –17.6 (–16, –19) –15.7 (–14, –17) 0.26 –17.3 (–16, –19) –16.1 (–14, –18) >0.99 0.59
MAPSE sept (cm/s) 12.5 (11.5–13.5) 12.1 (11.2–13.1) >0.99 12.6 (11.4–13.8) 11.1 (10.1–12.2) 0.02 0.09
MAPSE lat (cm/s) 11.5 (10.4–12.6) 11.2 (10.2–12.3) >0.99 11.2 (10.0–12.4) 11.0 (9.8–12.1) >0.99 0.96
E (cm/s) 72.0 (62.6–81.4) 68.1 (62.2–74.1) >0.99 78.8 (68.4–89.3) 64.1 (57.2–70.9) 0.01 0.09
A (cm/s) 67.8 (58.2–77.5) 74.6 (63.9–85.3) 0.37 82.0 (71.1–92.7) 83.7 (71.6–95.9) 0.98 0.41
E/A 1.08 (0.93–1.25) 0.95 (0.81–1.10) 0.43 0.97 (0.82–1.14) 0.77 (0.65–0.92) 0.03 0.39
NT–ProBNP (ηg/l) 93 (58–149) 108 (70–167) >0.99 65 (32–130) 154 (92–260) 0.05 0.07
Exercise test (W) 150 (135–165) 133 (115–151) 0.03 151 (133–151) 118 (96–140) 0.001 0.10
Preop cardiac function
Lund et al 2015
Chemotherapy Chemoradiotherapy
Variable Pre neoadjuvant Post neoadjuvant Pa Pre neoadjuvant
Post
neoadjuvant pa pb
EF (%) 59 (56–62) 57 (53–60) >0.99 60 (57–64) 59 (55–63) >0.99 0.80
GS (%) –17.6 (–16, –19) –15.7 (–14, –17) 0.26 –17.3 (–16, –19) –16.1 (–14, –18) >0.99 0.59
MAPSE sept (cm/s) 12.5 (11.5–13.5) 12.1 (11.2–13.1) >0.99 12.6 (11.4–13.8) 11.1 (10.1–12.2) 0.02 0.09
MAPSE lat (cm/s) 11.5 (10.4–12.6) 11.2 (10.2–12.3) >0.99 11.2 (10.0–12.4) 11.0 (9.8–12.1) >0.99 0.96
E (cm/s) 72.0 (62.6–81.4) 68.1 (62.2–74.1) >0.99 78.8 (68.4–89.3) 64.1 (57.2–70.9) 0.01 0.09
A (cm/s) 67.8 (58.2–77.5) 74.6 (63.9–85.3) 0.37 82.0 (71.1–92.7) 83.7 (71.6–95.9) 0.98 0.41
E/A 1.08 (0.93–1.25) 0.95 (0.81–1.10) 0.43 0.97 (0.82–1.14) 0.77 (0.65–0.92) 0.03 0.39
NT–ProBNP (ηg/l) 93 (58–149) 108 (70–167) >0.99 65 (32–130) 154 (92–260) 0.05 0.07
Exercise test (W) 150 (135–165) 133 (115–151) 0.03 151 (133–151) 118 (96–140) 0.001 0.10
Chemotherapy Chemoradiotherapy
Variable Pre neoadjuvant Post neoadjuvant Pa Pre neoadjuvant
Post
neoadjuvant pa pb
EF (%) 59 (56–62) 57 (53–60) >0.99 60 (57–64) 59 (55–63) >0.99 0.80
GS (%) –17.6 (–16, –19) –15.7 (–14, –17) 0.26 –17.3 (–16, –19) –16.1 (–14, –18) >0.99 0.59
MAPSE sept (cm/s) 12.5 (11.5–13.5) 12.1 (11.2–13.1) >0.99 12.6 (11.4–13.8) 11.1 (10.1–12.2) 0.02 0.09
MAPSE lat (cm/s) 11.5 (10.4–12.6) 11.2 (10.2–12.3) >0.99 11.2 (10.0–12.4) 11.0 (9.8–12.1) >0.99 0.96
E (cm/s) 72.0 (62.6–81.4) 68.1 (62.2–74.1) >0.99 78.8 (68.4–89.3) 64.1 (57.2–70.9) 0.01 0.09
A (cm/s) 67.8 (58.2–77.5) 74.6 (63.9–85.3) 0.37 82.0 (71.1–92.7) 83.7 (71.6–95.9) 0.98 0.41
E/A 1.08 (0.93–1.25) 0.95 (0.81–1.10) 0.43 0.97 (0.82–1.14) 0.77 (0.65–0.92) 0.03 0.39
NT–ProBNP (ηg/l) 93 (58–149) 108 (70–167) >0.99 65 (32–130) 154 (92–260) 0.05 0.07
Exercise test (W) 150 (135–165) 133 (115–151) 0.03 151 (133–151) 118 (96–140) 0.001 0.10
Chemotherapy Chemoradiotherapy
Variable Pre neoadjuvant Post neoadjuvant Pa Pre neoadjuvant
Post
neoadjuvant pa pb
EF (%) 59 (56–62) 57 (53–60) >0.99 60 (57–64) 59 (55–63) >0.99 0.80
GS (%) –17.6 (–16, –19) –15.7 (–14, –17) 0.26 –17.3 (–16, –19) –16.1 (–14, –18) >0.99 0.59
MAPSE sept (cm/s) 12.5 (11.5–13.5) 12.1 (11.2–13.1) >0.99 12.6 (11.4–13.8) 11.1 (10.1–12.2) 0.02 0.09
MAPSE lat (cm/s) 11.5 (10.4–12.6) 11.2 (10.2–12.3) >0.99 11.2 (10.0–12.4) 11.0 (9.8–12.1) >0.99 0.96
E (cm/s) 72.0 (62.6–81.4) 68.1 (62.2–74.1) >0.99 78.8 (68.4–89.3) 64.1 (57.2–70.9) 0.01 0.09
A (cm/s) 67.8 (58.2–77.5) 74.6 (63.9–85.3) 0.37 82.0 (71.1–92.7) 83.7 (71.6–95.9) 0.98 0.41
E/A 1.08 (0.93–1.25) 0.95 (0.81–1.10) 0.43 0.97 (0.82–1.14) 0.77 (0.65–0.92) 0.03 0.39
NT–ProBNP (ηg/l) 93 (58–149) 108 (70–167) >0.99 65 (32–130) 154 (92–260) 0.05 0.07
Exercise test (W) 150 (135–165) 133 (115–151) 0.03 151 (133–151) 118 (96–140) 0.001 0.10
Chemotherapy Chemoradiotherapy
Variable Pre neoadjuvant Post neoadjuvant Pa Pre neoadjuvant
Post
neoadjuvant pa pb
EF (%) 59 (56–62) 57 (53–60) >0.99 60 (57–64) 59 (55–63) >0.99 0.80
GS (%) –17.6 (–16, –19) –15.7 (–14, –17) 0.26 –17.3 (–16, –19) –16.1 (–14, –18) >0.99 0.59
MAPSE sept (cm/s) 12.5 (11.5–13.5) 12.1 (11.2–13.1) >0.99 12.6 (11.4–13.8) 11.1 (10.1–12.2) 0.02 0.09
MAPSE lat (cm/s) 11.5 (10.4–12.6) 11.2 (10.2–12.3) >0.99 11.2 (10.0–12.4) 11.0 (9.8–12.1) >0.99 0.96
E (cm/s) 72.0 (62.6–81.4) 68.1 (62.2–74.1) >0.99 78.8 (68.4–89.3) 64.1 (57.2–70.9) 0.01 0.09
A (cm/s) 67.8 (58.2–77.5) 74.6 (63.9–85.3) 0.37 82.0 (71.1–92.7) 83.7 (71.6–95.9) 0.98 0.41
E/A 1.08 (0.93–1.25) 0.95 (0.81–1.10) 0.43 0.97 (0.82–1.14) 0.77 (0.65–0.92) 0.03 0.39
NT–ProBNP (ηg/l) 93 (58–149) 108 (70–167) >0.99 65 (32–130) 154 (92–260) 0.05 0.07
Exercise test (W) 150 (135–165) 133 (115–151) 0.03 151 (133–151) 118 (96–140) 0.001 0.10

17. Periop inflammatory responses in the exposed lung
Chemo-
therapy
(n=15)
Chemoradio-
therapy
(n=11)
p
IL-1b 2.00 (1.37-2.73) 4.41 (2.65-6.43) 0.007
IL-6 6.52 (4.16-8.85) 8.94 (3.27-20.53) 0.16
IL-8 9.53 (2.28-14.41) 17.45 (2.36-29.24) 0.39
IL-10 3.71 (1.19-4.76) 4.24 (2.66-6.84) 0.28
MCP-1 7.10 (2.35-11-16) 9.65 (5.01-21.19) 0.16
CD45 32 (10-59) 26 (9-62) 0.53
Lund et al 2017 17
Median (range)
Chemo-
therapy
(n=15)
Chemoradio-
therapy
(n=11)
p
IL-1b 2.00 (1.37-2.73) 4.41 (2.65-6.43) 0.007
IL-6 6.52 (4.16-8.85) 8.94 (3.27-20.53) 0.16
IL-8 9.53 (2.28-14.41) 17.45 (2.36-29.24) 0.39
IL-10 3.71 (1.19-4.76) 4.24 (2.66-6.84) 0.28
MCP-1 7.10 (2.35-11-16) 9.65 (5.01-21.19) 0.16
CD45 32 (10-59) 26 (9-62) 0.53
pFi
10
20
30
40
50
60
Chemotherapy
Chemoradiotherapy
p=0.57
Pre Op POD 0 POD 1 POD 2 POD 3
pFi(PaO2/FiO2)

18. Meta‐analysis of postoperative morbidity and perioperative mortality in patients receiving neoadjuvant
chemotherapy or chemoradiotherapy for resectable oesophageal
and gastro‐oesophageal junctional cancers
Kumagai et al 2014

19. Meta‐analysis of postoperative morbidity and perioperative mortality in patients receiving neoadjuvant
chemotherapy or chemoradiotherapy for resectable oesophageal
and gastro‐oesophageal junctional cancers
Kumagai et al 2014

20. 285 patients screened for
inclusion
90
nCRT
104 excluded:
50 did not meet inclusion
criteria
36 declined to participate
18 other reason
91
nCT
181
80
underwent
surgery
80
underwent
surgery
78
underwent
resection
78
underwent
resection
Randomized
Klevebro et al 2014

21. nCRT n=78 nCT n=78 P-value
30 day mortality 0 0
90 day mortality 6 (8%) 2 (3%) 0.28
Surgical complication 28 (37%) 27 (35%) 0.73
- Anastomotic leak 10 (13%) 7 (9%) 0.45
Non-surgical complication 23 (31%) 16 (21%) 0.15
- Respiratory complication 17 (23%) 10 (13%) 0.14
-Cardiovascular complication 6 (8%) 4 (5%) 0.53
Any complication 40 (53%) 35 (45%) 0.30
Postoperative morbidity and mortality
Klevebro et al 2014

22. nCRT nCT P-value
Clavien-Dindo grade
I 1 0
II 9 7
IIIa 9 12
IIIb 14 8
IVa 4 4
IVb 0 0
V 5 1
Clavien-Dindo grade IIIb or higher 23 (30%) 13 (17%) 0.05
Median Clavien-Dindo IIIb IIIa 0.002
Severity of complications
Klevebro et al 2014

23. Causes of death during years 1–3 after randomization,
according to treatment allocation
p=0.0411 (46%)3 (15%)
Klevebro et al 2015

24. Mean estimated dose towards the gastric fundus was 17.3 Gy (95% CI 11.3 - 23.3)
Results II

25. • Neoadjuvant
chemoradiotherapy n=28.
• Non-RT n=42
• Esophagectomy with cervical
anastomosis.
The organ at risk for radiation induced damage

26. Whisker box plot of the distribution of Clavien Dindo grade
after an anastomotic dehiscence
The median score was IIIb in the non-RT group, and IVb in the nCRT group (p=0.002).
Klevebro et al 2016

27. Esophageal Neoplasia
Esophageal Squamous Cell Carcinoma ESCC
. The highest rates are found in Asia (China,
Singapore), and Iran. “Asian Belt”
. Enviromental Toxic Agents, play a key role
Esophageal Adenocarcinoma EAC
. The highest rates are found in developed
countries (adult causasian male)
. Generally associated with reflux disease,
Barrett esophagus and obesity
ESCC and EAC show many difference based on their
epidemiology, natural history and pathogenesis

31. Systematic review and meta-analysis on the significance of salvage esophagectomy
for persistent or recurrent esophageal squamous cell carcinoma
after definitive chemoradiotherapy
• A treatment-related mortality of 10.3% was recorded in patients who were
submitted to salvage esophagectomy, while it was impossible to perform a
meta-analysis comparing treatment-related mortality between the groups.
• Salvage esophagectomy offers significant gain in long-term survival
compared with second-line CRT
• Salvage esophagectomy is carried out at a price of a high treatment-related
mortality.
Kumagai et al 2016

32. • Main hypothesis:
– The overall survival after dCRT with surveillance and
salvage esophagectomy ”on demand ” is non-inferior (at
the 10% level) to the overall survival after nCRT+ surgery
• Secondary hypothesis
– The overall summarized HRQOL is better after dCRT (at
least 30%) than after nCRT + surgery at 6 months after
randomization
European multicenter RCT

33. Relative Risk of Lethality by Type of Cancer

34. Results after pancreatico-duodenectomy
0
2
4
6
8
10
12
14
16
18
20
'94-'95 '96-'97 '98-'99 '00-'01 '02-'03
< 5
5 - 9
10 - 24
> 24
mortalityrate(%)
n=428 n=441 n=487 n=474 n=555
hospital mortality per cluster
intervals
Gouma et al.

35. Pancreatic fistula formation and its consequences

40. Pankreas transected by use of staples

41. Ansorge et al 2013
The predictive value of plasma amylase values
for the subsequent development of ISGPF grade B/C

42. Ansorge et al 2013
The predictive value of drain amylase values for the
subsequent development of ISGPF grade B/C

43. Ansorge et al 2013
The predictive value of plasma CRP values for the
subsequent development of ISGPF grade B/C

44. • Adjuvant!
• Neoadjuvant?
• Preop/locally advanced?!
Pancreas cancer-
current and future therapeutic options

45. Slide 20
Presented By John Neoptolemos at 2016 ASCO Annual Meeting

48. Vein Resection – prognosis?

49. Conroy et al 2010

50. C and D1 cases - ”The Appleby procedure”
Klompmaker et al British Journal of Surgery; 103: 2016

51. Distal pancreatectomy with coeliac axis resection
Overall survival
Klompmaker et al British Journal of Surgery; 103: 2016
< 50 % neoadjuvant > 50 % neoadjuvant neoadjuvant unknown

54. Outcomes after extended pancreatectomy in patients with
borderline resectable and locally advanced pancreatic
cancer
Hartwig et al BJS 2016; 103: 1683–1694

55. 42.4
4.3
7.5
0 10 20 30 40 50
morbidity %
30 day mortality %
in hospital mortality
%
extended p-ectomy
standard p-ectomy
Outcomes after extended pancreatectomy in patients with
borderline resectable and locally advanced pancreatic cancer
Hartwig et al BJS 2016; 103: 1683–1694

56. 22
53.3
5.4
16.3
0 20 40 60
arterial resection %
morbidity %
30 day mortality %
in hospital mortality %
total p-ectomy (n=203)
total p-ectomy
(n=203)
Outcomes after extended pancreatectomy in patients with
borderline resectable and locally advanced pancreatic cancer
Hartwig et al BJS 2016; 103: 1683–1694

57. The Karolinska Experiences
Arterial resections during pancreatectomy for locally advanced pancreatic ductal
adenocarcinoma are feasible and superior to palliative chemotherapy
M Del Chiaro, Z Ateeb, N Sanjeevi, S Westermark, E Rangelova, U Arnelo, L Lundell,
R Segersvärd, and C Ansorge
Center for Digestive Diseases, Karolinska University Hospital, Stockholm Sweden
APC poster 2016

58. 34
66
54
3.1
0 20 40 60 80
arterial resection
alone %
arterial + vein
resection %
morbidity %
in hospital mortality
%
total p-ectomy (n=32)
total p-ectomy (n=32)
Del Chiaro et al APC poster 2016
Arterial resections during pancreatectomy for locally advanced pancreatic ductal
adenocarcinoma are feasible and superior to palliative chemotherapy
Category C and D1 cases

59. 66.4
20.7 20.7
0
10
20
30
40
50
60
70
1 year 3 year 5 year
extended resection
(n=32)
palliative treatment
(n=32)
Overall survival (%)
Del Chiaro et al APC poster 2016Del Chiaro et al APC poster 2016
Arterial resections during pancreatectomy for locally advanced pancreatic ductal
adenocarcinoma are feasible and superior to palliative chemotherapy
Category C and D1 cases (nonresponsive to neoadjuvant therapy)

60. Procedures waiting behind the corner

62. Intravenous fluid therapy – in hospital iv fluid therapy in adults
all cause mortality

63. Intravenous fluid therapy – in hospital iv fluid therapy in adults
Length of ICU stay

64. Intraoperative Fluid Restriction in Pancreatic Surgery:
A Double Blinded Randomised Controlled Trial
Busch et al 2015

65. • provoked vasodilatation
• large volume shifts
• hemodynamic instability
• vasopressors need
• large amounts of fluids
• risk for complications ?
Potential caveats confined to the use of EDA