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
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
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
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
• 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
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.
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
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
Outcomes after extended pancreatectomy in patients with
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)
Outcomes after extended pancreatectomy in patients with
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%
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 ductaladenocarcinoma are feasible and superior to palliative chemotherapy
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
Arterial resections during pancreatectomy for locally advanced pancreatic ductaladenocarcinoma are feasible and superior to palliative chemotherapy
Category C and D1 cases (nonresponsive to neoadjuvant therapy)
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