1. UPDATES OF IMMUNONUTRITION THERAPY IN SURGERY AND
Taiwan Surgical Association Meeting
Taipei - March 18, 2018
UPDATES OF IMMUNONUTRITION THERAPY IN SURGERY AND
ONCOLOGY PATIENTS
Marco
Braga
Professor
of Surgery
San Raffaele
University ,
Milan

2. Switching philosophy Nutritional therapy
( Braga, Clin Nutr 2016 )
Switching philosophy
Nutritional therapy
“ the classic concept “
Nitrogen and Energy to support
patients’ nutritional status
Indications:
Undernourished patients
Pharmaconutrition or Immunonutrition
Specific substrates to modulate inflammatory and immune response
Indications:
Patients undergoing GI cancer surgery regardless of their nutritional status

3. Perioperative Immunoinutrition
Plasma Arginine (mmol/L)
Plasma NO (mmol/L) 20 40 60 80
100
120
140
160 50 * * 40 * * 30 20 10
Days
Day + 8
- 8 1
- 1 2
+ 1 3 +4 4
+ 8 5 6
Day - 1
Control
Supplemented
Braga, Arch Surg 1996

5. PERIOPERATIVE IMMUNONUTRITION
Lower PGE2 serum level after surgery
Higher IFN-gamma production after surgery
Higher mRNA expression Th1 transcription factor
Modulate Th1 / Th2 differentiation
Suzuki, Surgery 2010
Aida, Surgery 2014

6. Gianotti, JPEN 1999

7. Perioperative Immunonutrition
G-I
cancer surgical patients
Author
Blinding IsoN
Pts
Infection
rate p
Braga ‘99
yes
yes
206
13 % vs
29 %
Senkal
‘99
yes
yes % vs
24 %

8. reimbursement rates (€)
Total costs
and DRG
reimbursement rates (€)
Conventional
Pre
-op IMN
Uncomplicated pts
184,725
229,208
Complicated pts
535,236
334,148
Nutrition
3,047
14,729
Total
578,085
723,368
DRG
reimbursement
781,392
740,301
Difference
58,024
162,216
Braga, Nutrition

9. Immunonutrition McClave JPEN 2013
Perioperative pharmaconutrition (formula containing arg, w-3 and nucleotides) has been shown to reduce infection, other complications, and LOS in patients undergoing major upper or lower gastrointestinal cancer surgeries, regardless of preexisting nutrition status. 9
McClave JPEN 2013

10. Latest Meta-analysis (83 RCTs, 7116 Pts )
IMNs reduced Infection Rate and LOS ( p< 0.001)
even after exclusion of high - risk of bias RCTs
RCTs
Infection rate
LOS
GLUTAMINE
p = 0.003
p < 0.001
ARGININE
p < 0.001
p = 0.003
OMEGA
p < 0.001
p < 0.001
RNA
p < 0.001
p < 0.001
Probst, Br J Surg

11. 264 well-nourished patients ( 75% laparoscopic surgery )
7 days before surgery days after surgery
Moya, Medicine 2016

12. Who benefit from immunonutrition?
Weimann A., Braga M., Carli F. et al Clin Nutr 2017
Who benefit from immunonutrition?
Patients with high risk for postoperative infections should receive perioperative immunonutrition even if operations including those for cancer have to be delayed.

13. THE OXIDATIVE STRESS VICIOUS CIRCLE
Ischemia/Reperfusion
Tissue cells infiltration
Oxygen compsuption
Cytokines release
ATP
AMP
ROS production
Xantine
dehidrogenase
Xantine
oxidase
Respiratory Burst reactions
Oxidative stress
NF-κB Macrophages activation
DNA, proteins
and lipid dammage
Cell death
Inflammation
Release of IL-1β,
TNF-α, Il-6, IL-8

14. ANTIOXIDANTS IN CRITICALLY ILL PATIENTS
MORTALITY
Heyland Int Care Med 2005

15. POSTOPERATIVE ENTERAL ANTIOXIDANTS
WELL TOLERATED AND METABOLICALLY SAFE
IMPROVEMENT IN ANTIOXIDANT CONCENTRATIONS
IMPROVEMENT IN ANTIOXIDANT DEFENSES
Preiser CCM
Nathens Ann Surg
Senkal Clin Nutr
Schroeder EJCN

16. ANTIOXIDANTS (BOOSTER (300 mL)
Vitamin C 750 mg
Vitamin E 250 mg
Selenium 150 μg
Zinc 10 mg
β-carotene 5 mg
Green tea extract 1 g
Glutamine 15 g
Glucose 50 g

17. PLACEBO CONTROLLED TRIAL
RANDOMIZED BLIND
PLACEBO CONTROLLED TRIAL
PANCREATIC RESECTION
1° Dose – 18 h
2° Dose
- 12 h
3° Dose
- 2 h
Baseline
D +1
D +3
D +7
D +30
T.A.C.
CRP
Antioxidants
T.A.C.
CRP
Antioxidants
T.A.C.
CRP
Antioxidants
T.A.C.
CRP
Antioxidants
Final visit
Braga, Nutrition 2012

18. ANTIOXIDANTS BOOSTER
Braga, Nutrition 2012

19. TOTAL ANTIOXIDANT CAPACITY*
*** **
* p = ** p = *** p = 0.001
Braga, Nutrition 2012

20. Quality of protein intake in cancer
TPN enriched with branched-chain A.-A.
improved albumin synthesis.
Tayek, Cancer 1986
Hunter, BJS 1989
TPN enriched with leucin and omega-3 fatty acids increased muscle protein synthesis.
Deutz, Clin Nutr 2011

21. Glutamine in cancer patients
Glutamine is a semi-essential A.-A. in catabolic conditions, including cancer.
Positive effect of Glutamine supplementation
on chemotherapy toxicity
Kuhn, Clin Nutr

22. Oral Glutamine reduces CT-RT toxicity
Head and Neck cancer Kaohsiung University. ClinicalTrials.gov 2017
Lopez-Vaquero Mol Clin Oncol 2017
Chattopadhyay, South Asian J Cancer 2014
Lung cancer Gul, Asian Pac J Cancer Prev 2015
Colorectal cancer Wang, The Oncologist
Mixed cancer Sayles, Nutr Clin Pract
Anderson, Cancer 1998

23. Body Composition assessed by CT Scan ( L3 )
in Pancreatic Cancer Surgical Patients
Subcutaneous Fat
Visceral Fat
Muscle Mass
Sarcopenia Rate : 64%
Severe Weight Loss : 25%
Pecorelli, Br J Surg 2016

24. Sarcopenia in Colorectal Cancer
Association with preoperative CRP
Association with T-stage and lymphatic invasion
Increased postoperative complications
Reduced overall and disease-free survival
Mie University Hospital

25. 60-day Mortality Following PD
Multivariate stepwise logistic regression
C-statistics index: 0.871
(95%CI: – 0.943)
Hosmer-Lemeshow test: p-value = 0.618
Pecorelli, BJS

26. PREHABILITATION Relaxation Techniques
MULTIMODAL APPROACH
Relaxation Techniques
Medical / Pharmacological Optimization
Physical Activity ( Aerobic, Respiratory )
Specialized Nutrition

27. Change in %LBM from baseline Change in % body fat from baseline
Prehabilitation changes body composition preop. and postop.
vvv
Change in %LBM from baseline
Change in % body fat from baseline
% of lean body mass (LBM) and fat measured using hand-to-foot bio-electrical impedance analyzer

28. IMMUNONUTRITION IN SURGERY
FUTURE TRENDS
Molecular signalling pathway
Dose - Response Studies
Sarcopenic patients
Neoadjuvant treatment