Surgery of pancreatic cancer

Gian Luca Grazi
Professor of Surgery – HepatoBiliaryPancreatic Surgery, AUO Careggi
Oncological treatment for
radical purposes
Surgery

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Gian Luca Grazi – HepatoBiliaryPancreatic Surgery, AOU Careggi
https://www.chirurgiadelfegato.it/pancreas/tumore-pancreas/tumore-alla-testa-del-pancreas/dcp/

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Pre-operative management
Neo-adjuvant chemotherapy
Centralization

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Ducreux M, Ann Oncol 2015: 26 (Supplement 5): v56–v68

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Should we drain the jaundiced patient ?
Jaundice is not an emergency situation!!!

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Outcome No PreOp Biliary
Drainage
Plastic Stent Metal stent Percutaneous
catheter
Any Post-operative
complication
80 (79%) 46 (50%) 47 (50%) 27 (22%)
Intraabdominal
infection
62 (64%) 34 (39%) 53 (57%) 52 (41%)
Post-operative
hemorrage
42 (40%) 49 (51%) 52 (58%) 58 (51%)
Wound infection 96 (88%) 19 (22%) 54 (51%) 31 (399%)
The probability that an approach is better than other approaches for a given clinical outcome (i.e. P-scores).
The best approach is highlighted
Lee PJ, HPB 2018;20:477-486

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250 µmol/l
=
14,62 mg/dl
van Gils L, HPB 2022;24:1888-1897
Flowchart (The displayed bilirubin levels are measured at diagnosis)
Preoperative biliary drainage in severely jaundiced patients
with pancreatic head cancer: A retrospective cohort study

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35
21
9
6
16
8
0
8
0
5
10
15
20
25
30
35
40
Any severe P.O.
complication
CD III CD IV In hospital Mortality
< 250 µmol/l > 250 µmol/l
van Gils L, HPB 2022;24:1888-1897
Surgery related endpoints; analysis based on
bilirubin level directly prior to surgery

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 Patients with pancreatic head cancer and cholestasis with a bilirubin 250 mmol/l
are comparable to patients with a lower bilirubin level and that there is no
evidence supporting a different approach regarding PBD in patients with severe
cholestasis.
 PBD should no longer be performed based on a high bilirubin level alone.
 There are still indications for PBD, for example cholangitis, refractory pruritus and
in the setting of neoadjuvant therapy, which is subject of extensive research and
increasingly applied in clinical practice.
 Whether a specific subgroup of patients with pancreatic head cancer and
cholestasis might benefit from PBD needs to be further evaluated.
van Gils L, HPB 2022;24:1888-1897

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Arterial Tumor Contact
Less than or equal
to 180°tumor
contact without
deformity.
More than 180°
tumor contact
without deformity.
Tumor contact with
deformity (arrow).
Al-Hawary MM, Gastroenterology 2014; 146: 291-304

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Venous Tumor Contact
Less than or equal
to 180°tumor
contact without
deformity.
Less than or equal
to 180°tumor
contact with
deformity (arrows).
More than 180°
tumor contact
without deformity.
Tear drop
deformity (arrows).
Al-Hawary MM, Gastroenterology 2014; 146: 291-304

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Resectable
R
Borderline Resectable
BR
Unresectable
UR
Venous Involvement alone
BR-PV
Arterial Involvement
BR-A
Locally advanced
LA
Metastatic
M
SMV/PV No contact or
unilateral narrowing
Tumor contact 180° or greater
or bilateral
narrowing/occlusion, not
exceeding the inferior border
of the duodenum
Bilateral
narrowing/occlusion,
exceeding the inferior
border of the duodenum
SMA, CA No tumor contact No tumor contact/invasion Tumor contact < 180°
without deformity/stenosis
Tumor contact/invasion
of 180° or more degree
CHA No tumor contact No tumor contact/invasion Tumor contact without
showing tumor contact of
the PHA and/or CA
Tumor/contact/invasion
of the PHA and/or CA
AO Tumor contact or
invasion
M Distant
metastases
Isaji S, Pancreat 2018, 18: 2-11
International Consensus of Classification of
Borderline Resectable Pancreatic Tumor
SMV: superior mesenteric vein, PV: portal vein, SMA: superior mesenteric artery, CA: celiac artery,
CHA: common hepatic artery, PHA: proper hepatic artery

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Centralization

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Ghaneh P, Lancet Gastroenterol Hepatol. 2023;8:157-168
ESPAC5 was a multicentre, randomised,
open-label, controlled, phase 2
feasibility trial.
The trial was done in 16 pancreatic
centres in the UK and Germany.

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 The results of ESPAC5 show that neoadjuvant short-course combination
chemotherapy was more effective than immediate surgery with adjuvant
therapy in the setting of borderline resectable pancreatic ductal
adenocarcinoma, and favoured neoadjuvant chemotherapy rather than
neoadjuvant chemoradiotherapy.
 The survival advantage of neoadjuvant therapy was seen despite no
significant difference being noted in resection rate.
 The results of this trial provide evidence for neoadjuvant short-course
chemotherapy in borderline resectable pancreatic ductal adenocarcinoma.
Ghaneh P, Lancet Gastroenterol Hepatol. 2023;8:157-168

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Drop out Rate:
35/90 (41.1%)
Allocated to
surgery:
10/33 (30.3%)
Allocated to
CHT:
25/57 (43.8%)
Planned:
100 patients

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Cucchetti A, Surgery. 2023:S0039-6060(23)00042-9. doi: 10.1016/j.surg.2023.01.016
Regret can be a consequence of the omission of potentially beneficial therapy and the commission
of treatment in the case that it was subsequently proved to be more harmful than beneficial.
• The regret of omission here refers to the regret felt by the physician who withheld neoadjuvant
therapy from a patient who otherwise may have benefited from this treatment.
• The regret of commission refers to the regret felt by the physician who decided to start
neoadjuvant therapy resulting in the loss of performing upfront surgery.

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TYPE OF REGRET QUESTION MEANING
Regret of omission “How would you rate the level of your
regret, on a scale of 0 to 100 (0 = no
regret, 100 = maximum regret) if you
decided NOT to start neoadjuvant
therapy and the patient died after
upfront surgery due to early tumor
relapse?”
Regret is here the consequence
of the missed opportunity to
control the tumor biology, so
that the patient was upfront
resected and eventually died
after tumor recurrence.
Regret of the commission “How would you rate the level of your
regret, on a scale of 0 to 100 (0 = no
regret, 100 = maximum regret) if you
started neoadjuvant therapy but the
patient’s disease ultimately became
unresectable and he/she died because
of cancer?”
Regret is here the consequence
of the decision to administer
neoadjuvant chemotherapy,
which ultimately prevented
undertaking a theoretically life-
prolonging surgery.

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 Different physicians working in different hospitals will likely make similar decisions for
PDAC patients with high-risk features but can decide differently on the same patient
who presents with intermediate or low biological risk.
 This particularly affects surgeons working in low/medium volume surgical units, who
are more prone to opt for upfront surgery.
 Given these differences, it would be preferable to make decisions in multidisciplinary
teams working, preferably, in high-volume hospitals to ensure that more consistent
elicitation of preferences can be achieved.

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Centralization

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Balzano G, Br J Surg. 2020 Oct;107(11):1510-1519
Mortality rates in each of
92 Italian hospitals with a
minimum volume of ten
resections per year
according to hospital
volume

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 The great majority of Italian hospitals performing pancreatic resections fall
into the very low-volume category, with an observed mortality rate more than
three times higher than that of hospitals with the highest volume.
 If all patients had received the standard of treatment offered by very high-
volume hospitals, 396 of 789 deaths (50⋅2 per cent) would have been avoided.

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Geographical distribution of Italian hospitals with a minimum volume of ten patients and
maximum risk-standardized mortality rate of less than 5 or 5–10 per cent, in relation to Italian
population density

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Failure to Rescue
High-mortality hospitals may not be as proficient at
recognizing and managing serious complications
once they occur
Ghaferi AA, Ann Surg 2009;250: 1029 –1034

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Complication Incidence and Failure to Rescue Rates Between “Best”
and “Worst” Hospitals for All High-Risk Operations Combined

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Mortality, complication, and failure to rescue rates for
all operations combined.

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Failure to rescue rates for 6 major operations

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180
202
230
239
266
203
222
270
258
249
260 261
8.11 5.26 6.88 6.06 5.36 6.29 5.26 4.93 6.93 5.5 4.19 5.26
0
50
100
150
200
250
300
2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021
# cases p.o. mortality
Number of Pancreatic Resection for Cancer
in Tuscany
Fonte dati: https://www.ars.toscana.it/banche-dati/dati-sintesi-sintprosero-aggiornamenti-sugli-indicatori-di-esito-per-ospedale-in-toscana-quali-mortalita-riammissioni-e-volumi

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103
36
8 8
1
118
33
5
14
3
129
56
10
14
3
152
40
8 9
4
145
33
23 21
2
143
44
26
20
7
168
30
18 20
13
0
20
40
60
80
100
120
140
160
180
Center #1 Center #2 Center #3 Center #4 Center #5
#
of
cases
2015 2016 2017 2018 2019 2020 2021
Fonte dati: Programma Nazionale Esiti, Edizione 2022, https://pne.agenas.it/
Number of Pancreatic Resection for Cancer
in Tuscany, per Center

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0.58
2.18
0
22.7
1.17
3.41
0
6.77
3.03
1.82
0
18.13
0
1.84
0
4.82
1.2
2.9
7.1
4.02
2.4
1.69
6.95
6.21
2.72
11.7
0
10.19
0
5
10
15
20
25
Center #1 Center #2 Center #3 Center #4 Center #5
%
30-day
mortality
2015 2016 2017 2018 2019 2020 2021
Fonte dati: Programma Nazionale Esiti, Edizione 2022, https://pne.agenas.it/
30-day Mortality for Pancreatic Resection for Cancer
in Tuscany, per Center

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29
47
52
43
66
53 54
71
38 38
10
16
34
27 28
40
36
30
44
20 21
7
0
10
20
30
40
50
60
70
80
2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023
Total Whipple
Pancreatic Resections at AOU Careggi

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1
3
8
10
8
2
5
9
15
21
31
10
4
26
39
42
33
49
43
40
44
7
2
0
2
9
3 4 5 4 5
6
2 1
7 6
0
0
10
20
30
40
50
60
2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023
Unit 1 Unit 2 Unit 3 Unit 4
Pancreatic Resections at AOU Careggi

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As surgeons acquired a better understanding of surgical anatomy and physiology,
perioperative management improved, surgery expanded and training programs developed.
Modern surgery demonstrates potentially curative treatment options when facing a patient
with tumors including ablative techniques, open or minimal access surgery, and organ
transplantation.
Preoperative selection of the therapeutic approach should consider the staging of primary
cancer, concomitant diseases, and the patient's performance status.
A twenty-one-century surgeon must be equipped with excellent theoretical and clinical skills
to perform a precise operation.
Modern surgeons need to acquire high-level knowledge about the various surgical
procedures and techniques available to perform a oncological correct procedure.
Modern concept of surgical oncology

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A preoperative molecular prognostic nomogram for
resectable pancreatic cancer.
Dreyer SB, Ann Surg. 2020;272:366-376
A nomogram, also called a nomograph,
alignment chart, or abac, is a graphical
calculating device, a two-dimensional diagram
designed to allow the approximate graphical
computation of a mathematical function.
The field of nomography was invented in 1884
by the French engineer Philbert Maurice
d'Ocagne (1862–1938) and used extensively for
many years to provide engineers with fast
graphical calculations of complicated formulas
to a practical precision.

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• Ilenia Bartolini
• Giacomo Batignani
• Lorenzo Bruno
• Giancarlo Freschi
• Luca Moraldi
• Maria Novella Ringressi
• Matteo Risaliti
• Antonio Taddei

Oncological treatment for radical purposes - Surgery
Gian Luca Grazi
Professor of Surgery – HepatoBiliaryPancreatic Surgery AOU Careggi
gianluca.grazi@unifi.it
www.chirurgiadelfegato.it

Surgery of pancreatic cancer

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