critical care aspects of gi surgery by professor lars lundell

Esophagectomy

postoperative morbidity

30-50%

4

Can we make the train smaller?

21/01/2018Name Surname

Transthoracic vs transhiatal esophagectomy

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

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

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

Transition from open to minimally invasive esophagectomy from 2011 to 2016.

Rouvelas et al 2017

Preoperative risk assessment and prevention in esophageal cancer surgery

Grotenhuiset al 2010

Still competitive

Preoperative risk assessment and prevention (?) in esophageal cancer surgery

Radiationexposure and damage tosurroundingorgans

Echocardiographic findings

14/10/2015 Name Surname 15Lund 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

Preop cardiac function

Lund et al 2015



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



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



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



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

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

60ChemotherapyChemoradiotherapy

p=0.57

Pre Op POD 0 POD 1 POD 2 POD 3

pF

i (P

aO

2/F

iO2)

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

285 patients screened for inclusion

90 nCRT

104 excluded:

50 did not meet inclusioncriteria

36 declined to participate

18 other reason

91 nCT

181

80 underwent

surgery

80 underwent

surgery

78 underwentresection

78underwentresection

Randomized

Klevebro et al 2014

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

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

Causes of death during years 1–3 after randomization, according to treatment allocation

p=0.0411 (46%)3 (15%)

Klevebro et al 2015

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

Results II

• Neoadjuvant chemoradiotherapy n=28.

• Non-RT n=42

• Esophagectomy with cervicalanastomosis.

The organ at risk for radiation induced damage

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

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

Systematic review and meta-analysis on the significance of salvage esophagectomyfor 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

• 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

Relative Risk of Lethality by Type of Cancer

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

mo

rta

lity

ra

te (

%)

n=428 n=441 n=487 n=474 n=555

hospital mortality per cluster

intervals

Gouma et al.

Pancreatic fistula formation and its consequences

Pankreas transected by use of staples

Ansorge et al 2013

The predictive value of plasma amylase values

for the subsequent development of ISGPF grade B/C

Ansorge et al 2013

The predictive value of drain amylase values for the

subsequent development of ISGPF grade B/C

Ansorge et al 2013

The predictive value of plasma CRP values for the

subsequent development of ISGPF grade B/C

• Adjuvant!

• Neoadjuvant?

• Preop/locally advanced?!

Pancreas cancer-

current and future therapeutic options

Presented By John Neoptolemos at 2016 ASCO Annual Meeting

Vein Resection – prognosis?

Conroy et al 2010

C and D1 cases - ”The Appleby procedure”

Klompmaker et al British Journal of Surgery; 103: 2016

Distal pancreatectomy with coeliac axis resectionOverall survival

Klompmaker et al British Journal of Surgery; 103: 2016

< 50 % neoadjuvant > 50 % neoadjuvant neoadjuvant unknown

Outcomes after extended pancreatectomy in patients with

borderline resectable and locally advanced pancreatic

cancer

Hartwig et al BJS 2016; 103: 1683–1694

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


borderline resectable and locally advanced pancreatic cancer

Hartwig et al BJS 2016; 103: 1683–1694

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)


borderline resectable and locally advanced pancreatic cancer

Hartwig et al BJS 2016; 103: 1683–1694

The Karolinska Experiences

Arterial resections during pancreatectomy for locally advanced pancreatic ductaladenocarcinoma 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

34

66

54

3.1

0 20 40 60 80

arterial resectionalone %

arterial + veinresection %

morbidity %

in hospital mortality%



Del Chiaro et al APC poster 2016


Category C and D1 cases

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


Category C and D1 cases (nonresponsive to neoadjuvant therapy)

Procedures waiting behind the corner

Intravenous fluid therapy – in hospital iv fluid therapy in adultsall cause mortality

Intravenous fluid therapy – in hospital iv fluid therapy in adultsLength of ICU stay

Intraoperative Fluid Restriction in Pancreatic Surgery: A Double Blinded Randomised Controlled Trial

Busch et al 2015

• provoked vasodilatation

• large volume shifts

• hemodynamic instability

• vasopressors need

• large amounts of fluids

• risk for complications ?

Potential caveats confined to the use of EDA

critical care aspects of gi surgery by professor lars lundell

Health & Medicine