Clinical Nutrition 33 (2014) 649e654

Contents lists available at ScienceDirect

Clinical Nutrition
journal homepage: http://www.elsevier.com/locate/clnu

Original article

Cost-effectiveness analysis of immune-modulating nutritional support

for gastrointestinal cancer patientsq
Hélène Chevrou-Séverac a, *, Christophe Pinget b, Yannick Cerantola c,
Nicolas Demartines c, Jean-Blaise Wasserfallen b, Markus Schäfer c
a
Nestlé Health Science, Avenue Nestlé 55, BP 353, CH-1800 Vevey, Switzerland
b
University Hospital of Lausanne (CHUV), Medical Direction, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland
c
University Hospital of Lausanne (CHUV), Department of Visceral Surgery, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland

a r t i c l e i n f o s u m m a r y

Article history: Background & aim: Immune-modulating nutritional formula containing arginine, omega-3 fatty acids
Received 27 March 2013 and nucleotides has been demonstrated to decrease complications and length of stay in surgical patients.
Accepted 5 September 2013 This study aims at assessing the impact of immune-modulating formula on hospital costs in gastroin-
testinal cancer surgical patients in Switzerland.
Keywords: Method: Based on a previously published meta-analysis, the relative risks of overall and infectious
Immune-modulating formula
complications with immune-modulating versus standard nutrition formula were computed. Swiss
Post-surgical complication risk
hospital costs of patients undergoing gastrointestinal cancer surgery were retrieved. A method was
Cost-effectiveness analysis
Gastrointestinal cancer surgery
developed to compute the patients’ severity level, not taking into account the complications from the
surgery. Incremental costs of complications were computed for both treatment groups, and sensitivity
analyses were carried out.
Results: Relative risk of complications with pre-, peri- and post-operative use of immune-modulating
formula was 0.69 (95%CI 0.58e0.83), 0.62 (95%CI 0.53e0.73) and 0.73 (95%CI 0.35e0.96) respectively.
The estimated average contribution of complications to the cost of stay was CHF 14,949 (V10,901) per
patient (95%CI 10,712e19,186), independently of case’s severity. Based on this cost, immune-modulating
nutritional support decreased costs of hospital stay by CHF 1638 to CHF 2488 per patient (V1195
eV1814). Net hospital savings were present for baseline complications rates as low as 5%.
Conclusion: Immune-modulating nutritional solution is a cost-saving intervention in gastrointestinal
cancer patients. The additional cost of immune-modulating formula are more than offset by savings
associated with decreased treatment of complications.
Ó 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

1. Introduction
Complications following gastrointestinal (GI) cancer surgery are
still an important issue and significantly impact on patient’s
outcome, length of hospital stay (LOS) and costs.1,2 Reported post-
Non-standard abbreviations: IMF, immune-modulating formula; GI, gastroin-
testinal; DRG, diagnostic-related group; RR, relative risk; LOS, length of hospital
stay; CHF, Swiss franc.
q Conferences presentations: This paper has been presented as: (1) A poster
presentation at the 24th Annual Congress, European Society of Intensive Care
Medicine, October 1e5, 2011, Berlin, Germany. (2) An oral presentation at the 23rd
Annual Congress ALASS (Association latine d’analyse des systèmes de santé),
September 9e11 of 2012, Lisboa, Portugal. (3) An oral presentation at the 9th HTAi
conference (Health Technology Assessment international), June 25e27th of 2012,
Bilbao, Spain.
* Corresponding author. Tel.: þ41 21 924 79 22.
E-mail address: helene.chevrouseverac@nestle.com (H. Chevrou-Séverac).
operative complication rates for GI cancer surgery are ranging from
15% to 54%,3e7 with infectious complications being the most
frequent ones (including wound infections, abdominal abscess,
pneumonia, anastomotic dehiscence, urinary tract infections, and
sepsis). Policies to prevent and reduce post-operative complica-
tions generally focus on pathogen eradication, e.g. peri-operative
antibiotic prophylaxis, reduction of surgical trauma and intra-
operative contamination, as well as improvement in the hospital
environment.8 Only recently, improving host defense mechanisms
have become a target of interest.
Adequate nutrition is strongly linked with immune competence
and risk reduction of infections5,7; hence any nutritional depriva-
tion increases patient’s risk. Immune-modulating nutritional for-
mulas (IMF) have been studied in multiple randomized clinical
trials. Most of them have shown a reduction in post-operative in-
fectious and non-infectious complications as well as LOS in patients

0261-5614/$ e see front matter Ó 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
http://dx.doi.org/10.1016/j.clnu.2013.09.001

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650 H. Chevrou-Séverac et al. / Clinical Nutrition 33 (2014) 649e654

undergoing GI cancer surgery. Although some studies were not Table 1

conclusive due to either the IMF used, as formulas are not identical ICD codes related to GI cancer patients.

and therefore don’t reach the same clinical efficacy,6 or compliance Main diagnostic ICD-10 codes
issues,9,10 when studies were pulled together in meta-analyses, (C15) Malignant neoplasm of esophagus (ICD-10 codes selected: C15.0;
results have been consistently showing benefit of IMF in GI surgi- C15.4e5; C15.8e9)
cal patients.3e7,11 The most recent meta-analyses of RCTs in GI (C16) Malignant neoplasm of stomach (ICD-10 codes selected: C16.0e9 except
surgery are the ones of Cerantola et al. (2011),5 Marimuthu et al. C16.7)
(C17) Malignant neoplasm of small intestine (ICD-10 codes selected: C17.0e2
(2012)7 and Zhang et al. (2012).11 Cerantola’s study focused on all GI
and C17.8e9)
cancer surgeries, whereas Marimuthu’s one assessed only major (C18) Malignant neoplasm of colon (ICD-10 codes selected: C18.0e9)
open GI surgery; while Zhang and coauthors focused on surgeries (C19) Malignant neoplasm of rectosigmoid junction
for GI cancer patients. (C20) Malignant neoplasm of rectum
(C25) Malignant neoplasm of pancreas (ICD-10 codes selected: C25.0e3 and
In addition of meta-analyses3e7,11 demonstrating the efficacy of
C25.8e9)
IMF versus standard of care (SoC, i.e. nil-by-mouth and/or standard (C26) Malignant neoplasm of other and ill-defined digestive organs (ICD-10
enteral nutrition depending on the IMF regimen), several cost- codes selected: C26.8e9)
effectiveness analyses and cost impact studies of IMF have been (C78.7) Secondary malignant neoplasm of liver
published.1,12e14 The impact of IMF on hospital costs has been
studied in GI cancer surgery in Germany,12 Italy1,13 and the US.14 All
these trials demonstrated that IMF is a cost-effective and cost- ones included into the meta-analysis of Cerantola et al.5 were
saving intervention, independent of the IMF regimen. However, retrieved (see Tables 1 and 2 for the list of GI cancer diagnoses and
none of these studies took into account the patients’ severity level surgical interventions). Their medical records provided information
to isolate cost of care related to the index disease and interventions. on diagnoses, interventions, comorbidities, LOS, costs and DRG
The goal of this study was to fill this gap by assessing the cost- codes. Patients with overall and infectious complications linked to
effectiveness of IMF from a Swiss hospital diagnostic-related surgery that were potentially preventable with IMF intervention
group (DRG) cost database, while discarding the impact of pa- were coded as patients with complications (see Table 3 for the
tients’ severity level on these costs. selected complications). Based on the meta-analysis of Waitzberg
et al. (2006),3 these likely preventable complications with IMF were
2. Methods identified to be wound infections, anastomotic leaks and their
consequent infections, pneumonia and abdominal abscesses. From
2.1. Clinical outcomes this database extraction, average costs of hospital stay for the GI
cancer surgical patients with and without complications were
This cost-effectiveness analysis of IMF in GI patients used the computed.
clinical evidence from the Cerantola’s meta-analysis5 in order to
have clinical practice close to one of the Swiss hospital from which 2.2.2. Disease severity and cost of stay due to complications
cost data were extracted for the economic analysis. We used the In order to distinguish between costs related to treating com-
same 21 RCTs as included in this meta-analysis of RCTs comparing plications from costs linked to the patient’s comorbidities and/or
IMF versus SoC (standard enteral nutrition or nil-by-mouth) in GI disease severity, corrected cost-weights were computed by using
cancer patients undergoing elective surgery,5 to determine the Diagnosis Related Groups (DRG) to derive an exogenous severity
relative risks (RR) of overall and infectious complications of IMF score for each patient stay. In a DRG system, patient stays are
compared to SoC. Among these 21 studies, 6 focused on pre- classified in homogeneous groups on the basis of age, gender,
operative use of IMF, 12 on post-operative use of IMF and 6 on diagnostic and intervention codes. Patient stays grouped in the
peri-operative administration of IMF (see Cerantola et al.5 for more same DRG are assumed to have comparable costs. To each DRG, a
details). The studies selected by Cerantola and coauthors are not severity score called cost-weight (CW) is assigned. This CW was
presented in this publication. The RR computed here are just used to derive the patient’s exogenous severity score. For patients
complementary results to this meta-analysis in order to be used in a without complications, the exogenous severity score is equal to the
straightforward way into the cost-effectiveness analysis. current CW. However for the patients with complications, the CW
The computation of RR was performed using Review Manager they would have had in absence of complication was calculated to
Software for WindowsÒ (RevManÒ 5.0.23; The Nordic Cochrane identify their exogenous severity score (meaning independent of
Centre, Copenhagen Denmark), by a treatment effects analysis, the complications studied). The relevant complication codes were
with 95% confidence intervals (CI). Data across studies were pooled discarded from the patients’ record and a new DRG computed
using fixed-effects (inverse variance) and random-effects models. which represents the severity of patient’s profile independent of
his/her complications. Finally the contributions of complications
2.2. Cost outcomes and of patient’s severity level to the cost of hospital stay were both
estimated by regression analysis using Stata Statistical Software:
2.2.1. Hospital cost database Release 11 (StataCorp 2009).
Cost data were obtained from the university hospital of Lau-
sanne (CHUV) from its accounting and diagnostic-related group
Table 2
(DRG) database (thereafter, hospital database) for the years 2006e ICD codes related to GI surgeries.
2010. Based on their diagnostic (ICD-10-CMd) and intervention
List of interventions code ICD 9: GI surgeries
codes (ICD-9-CMe), hospital records of patients matching with the
42.19 42.33 42.39 42.4 42.41 42.42 42.52 42.54 42.58
42.59 42.62 42.63 42.65 42.69 42.99 43.5 43.6 43.7
d 43.89 43.91 43.99 45.31 45.33 45.34 45.41 45.43 45.49
International Classification Disease, 10th revision, Clinical Modification, World
45.61 45.62 45.71 45.73 45.74 45.75 45.76 45.79 45.8
Health Organization, http://www.who.int/classifications/icd/en/.
e 45.91 45.92 45.93 45.94 45.95 46.99 49.99 50.23 50.25
International Classification Disease, 9th revision, Clinical Modification, World
50.26 52.01 52.09 52.22 52.51 52.52 52.53 52.7 52.96
Health Organization.

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 H. Chevrou-Séverac et al. / Clinical Nutrition 33 (2014) 649e654 651

Table 3
ICD codes used to classify complications likely preventable with IMF.

ICD-10 diagnostic codes used to identify complications and infections

Sepsis A41.1 A41.2 A41.5 A41.51 A41.52 A41.58 A41.8 A41.9 N39.0 R65.0
Infections A49.0 A49.1 A49.8 A49.9
Pneumopathies J15.0 J15.2 J15.6 J18.0 J18.1 J18.9
Other complications K91.3 K91.8

2.2.3. Hospital cost impact and cost-effectiveness analyses
The resulting estimated treatment cost of complications was
then used to compute the impact of IMF versus SoC on hospital
costs for GI cancer patients undergoing surgery. For each patient’s
group, the costs of complications were computed by multiplying
the percentage of patients presenting with overall complications by
the cost of treating these complications. The hospitalization costs
related to exogenous patient’s severity score were not taken into
account, as assumed to be unrelated to the effect of IMF. Finally, the
cost-effectiveness of IMF intervention compared to SoC was
computed by comparing both cost of complications and medical
nutrition and complications rates between the two treatment
groups.
2.2.4. Sensitivity analyses
In order to also assess the robustness of the model, sensitivity
analyses were performed. First, results were computed around the
baseline complication rate which was varied between 0% and 60%.
The difference in hospital cost per patient were computed for each
complication rate and plotted against the baseline complications
rate for each IMF regimen. The baseline complication rate at which
difference in costs between groups was null (also called cost-
neutrality) was also estimated for the three regimen of IMF use.
Second, results were estimated for RR of infectious complications to
get a crude estimate of the impact of IMF regimen on cost of in-
fections. Here as well, the initial infection rate, making INF a cost-
neutral intervention was computed. Finally, uncertainty in param-
eters was also taken into account by one-way sensitivity analysis
using 95% confidence interval values for the RR of complications
and the RR of infections.
3. Results
3.1. Clinical outcomes (Tables 4 and 5)
RR of infectious complications and overall complications based
on the 21 trials included in the meta-analysis by Cerantola and
coauthors5 are displayed in Tables 4 and 5. The decreases in risks of
complications were always statistically significant, but more
important for infectious complications (RR ¼ 0.48e0.65) than for
overall complications (RR ¼ 0.62e0.73). The effect of IMF to reduce
the overall complication rate was more important when IMF was
used peri-operatively (RR of 0.62, with 95%CI 0.53e0.73); whereas
for infectious complications, the decrease was more important
when IMF was administered pre-operatively (RR of 0.48, with 95%
CI 0.35e0.66).
3.2. Hospital cost data and case’s severity
Four hundred and twenty patients with diagnosis and operation
codes related to GI cancer and surgery were extracted from the
hospital DRG database. These patients were selected based on the
diagnostic and intervention codes related to major GI surgery
related to use of IMF as recommended in ESPEN Guidelines (Grade A
recommendation).15 These patients underwent major GI surgery
into this hospital between January 2006 and December 2010. All
patients underwent routine pre-operative nutritional assessment at
the outpatient department by using the Nutritional Risk Score
(NRS).16 Patients having a NRS 3 were further assessed and treated
by the clinical nutrition team according to ESPEN guidelines.15 If
necessary, surgery was delayed up to two weeks. In addition be-
tween October 2007 and September 2010, 152 of these patients
were included into a randomized clinical trial assessing the efficacy
of pre-operative IMF compared to standard enteral nutrition on
post-operative complications rate in patients at nutritional risk.9
Consequently some of these patients might have used less health-
care resources than a true control group due to either the usual
standard nutrition protocol or to the trial done. Therefore using cost
data from this hospital was a conservative approach, as it may have
driven the hospital costs estimation down. This assumption was
confirmed as only 64 patients over the 420 selected presented with
complications giving a post-operative complication rate of 15.2%, far
below the rates usually seen in control groups of RCTs (ranging from
31% to 95% for overall complications when considering the RCTs
included in Cerantola’s meta-analysis5).
From these DRG data, the average exogenous severity scores
were estimated to amount to 4.05 (SD 1.85) for the 64 patients
presenting with at least one complication, and 2.84 (SD 1.21) for
patients without complication. This difference demonstrates that
patients with complications are more severely ill than those
without it, independently of the complications studied.
The average cost of hospital stay for the 420 cancer patients
(with and without infectious complications) undergoing lower and
upper GI surgery was CHF 33,549 (SD 21,955) per patient-stay
(V24,464). The mean hospital cost of stay for patients without
and with complications was CHF 29,499 (SD 17,587) and CHF
56,072 (SD 29,239) per patient-stay respectively (V21,511 and
V40,889). Patients without complications staid on average 12.76
days (with SD of 7.11) into hospital; while patients with compli-
cations staid 22.92 days (10.32). The contribution to the cost of
hospital stay of treating complications was estimated by a regres-
sion analysis taking into account the severity scores of the patients:
it led to additional CHF 14,949 (V10,901) per patient-stay (95%CI
CHF 10,712e19,186) (see Table 6).

Table 4 Table 5
Relative risk of overall complications for the 3 regimen of IMF; computed by meta- Relative risk of infectious complications for the 3 regimen of IMF; computed by
analysis. meta-analysis.

IMF regimen Relative risk 95% confidence Pooled complication IMF regimen interval Relative risk 95% confidence Pooled infection
of complications interval rate  control of infections interval rate  control

Pre-operative 0.69 0.58e0.83 53% Pre-operative 0.48 0.35e0.66 36%

Post-operative 0.73 0.35e0.96 50% Post-operative 0.65 0.53e0.79 29%
Peri-operative 0.62 0.53e0.73 54% Peri-operative 0.50 0.38e0.66 29%

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Table 6
Estimated cost of hospital stay due to case’s severity and complications (estimated
by regression analysis).

Estimated costs 95% confidence interval P

Exogenous severity CHF 9637 CHF 8546; 10,728 <0.001

score
Complications CHF 14,949 CHF 10,712; 19,186 <0.001

For non-malnourished patients, IMF is recommended to be

taken orally 3 times a day prior to surgery for 5e7 days; whereas for
malnourished patients the recommended intake is 3 times a day
orally for 5e7 days prior to surgery and 5 times a day orally (or 2 to
3 enteral pouches) for minimum 7 days. Thus the cost of IMF for
well-nourished patients was CHF 200 for the pre-operative
regimen for 5 days and a minimum of CHF 580 for the peri-oper-
ative regimen (either oral or enteral) for malnourished patients for
5 days pre- and minimum 7 days post-surgery (Nestlé Health Sci-
ence list prices as of 2010).
3.3. Cost-effectiveness analysis
Treatment costs of complications were computed for patients in
the IMF and control groups (Table 7). Considering the pre-operative
use of IMF therapy, in the SoC group, the pooled average compli-
cation rate was estimated to be 53%. Hence, based on the marginal
costs of CHF 14,949 (V10,901) for treating complications, this cost
of treating complication were multiplied by the complication rate
of the control group leading to an incremental average costs of
treating complications in the control group of CHF 7923 (5778V)
per patient. With the use of IMF, complications decreased from
53.0% in SoC to 36.6% (RR 0.69). The average incremental cost of
treating complications in the IMF group was computed like in the
control group while adding cost of IMF: it led to CHF 5667 (V4132)
per patient including costs of IMF. Thus, hospitals could save CHF
2256 (V1645) per patient’s hospitalization (95%CI [CHF 1560;
2952]) by decreasing the risk of overall complications with the
prescription of IMF pre-operatively. When doing the same calcu-
lation for peri-operative use of IMF, the estimated savings
amounted to an average of CHF 2488 (V1814) per patient (95%CI
[CHF 1618; 3357]) and to an average of CHF 1638 (V1195) per pa-
tient with post-operative use of IMF (95%CI [CHF 1066; 2210])
(Table 7). Thus in the three IMF regimen, overall complications as
well as treatment costs decreased, making IMF a more effective and
cost-saving intervention compared to Soc.
Fig. 1. Estimated cost-savings depending on the initial complications rate in the
control group (pre-operative regimen). Vertical axe’s title: Savings per patient’s stay in
Swiss francs. Horizontal axe’s title: Baseline complication rate.
hospitals. Considering pre-operative use of IMF, hospitals can still
achieve net savings of CHF32 (V23) per patient if baseline in-
fections rate in GI cancer surgical patient is as low as 5% (see Fig. 1).
The baseline complication rates at which there is no difference in
cost of complications (also called cost-neutral baseline rate) be-
tween the control and the intervention groups were estimated to
be 4.32%, 10.21% and 9.41% for the pre-, peri- and post-operative
regimen of IMF. For initial complication rates above these thresh-
olds, introducing IMF in the protocol of care for treating GI cancer
patients undergoing surgery could generate savings in hospital
costs (Table 8).
When considering only the infectious complications into the
cost-effectiveness analysis, here as well IMF was deemed as a
dominant intervention as it decreased risk of infection and cost of
care. The savings were respectively CHF 2598, CHF 1588 and CHF
1137 per patient for the pre-, peri- and post-operative use of IMF
respectively (respectively V1895; V1158 and V829). Similarly when
making the baseline infection rates varied in the control group, the
cost-neutral baseline infection rates was found to be 2.57%, 7.76%
and 7.27% for pre-, peri- and post-operative use of IMF (Figs. 1e3).
For initial infection rate above these thresholds, hospitals are ex-
pected to make savings when introducing IMF in their medical
practice (Table 8).
Finally, when taking into account 95%CI of RR of complications,
the range of cost of stay for treating complication always demon-
strated savings for pre and peri-operative use of IMF, whereas it
wasn’t the case for post-operative use; while when considering 95%
CI of RR of infections, the range of hospital cost shown that the IMF
intervention was always cost-saving (Table 8).
4. Discussion

This study demonstrated that IMF, by decreasing complications,

3.4. Sensitivity analyses
decreased net hospital cost, making it a more effective and cost-
saving intervention compared to SoC (called also dominant inter-
In real life, baseline complications rates in the control group
vention). Indeed, costs of IMF were offset by the savings due to the
could be different, depending on medical practice in different
decrease in hospital complications costs.

Table 8
Table 7
Results of the sensitivity analyses for the pre-, peri- and post-operative use of IMF.
Hospital cost of stay in the IMF and control groups based on relative risk of
complications. Pre-operative Peri-operative Post-operative
regimen regimen regimen
IMF Complication rate Marginal hospital costs
regimen Cost-neutral baseline 4.32% 10.21% 9.41%
RR SoC IMF SoC (95%CI) IMF (95%CI) Difference
complication rate
(IMF  Soc)
Savings per patient based on CHF 1147; CHF 1600; CHF 81;
(95%CI)
95%CI of RR of complications 3128 3214 þ4478
Pre-op 0.69 53.0% 36.6% CHF 7923 CHF 5667 CHF 2256 Savings based on infection CHF 2598 CHF 1588 CHF 1137
(5677; 10,169) (4117; 7216) (1560; 2952) rate per patient (95%CI) (1805; 3392) (973; 2202) (707; 1567)
Peri-op 0.62 54.0% 33.5% CHF 8072 CHF 5585 CHF 2488 Cost-neutral baseline 2.57% 7.76% 7.27%
(5784; 10,360) (4166; 7003) (1618; 3357) infection rate
Post-op 0.73 50.0% 36.5% CHF 7475 CHF 5836 CHF 1638 Savings based on 95%CI CHF 1630; CHF 894; CHF 530;
(5356; 9593) (4290; 7383) (1066; 2210) of RR of infections 3298 2108 1658

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 H. Chevrou-Séverac et al. / Clinical Nutrition 33 (2014) 649e654
Fig. 2. Estimated cost-savings depending on the initial complication rate in the control
group (peri-operative regimen). Vertical axe’s title: Savings per patient’s stay in Swiss
francs. Horizontal axe’s title: Baseline complication rate.
Our results are in concordance with four other studies assessing
the cost-effectiveness and impact on hospital costs of IMF in GI
cancer patients’ population undergoing elective surgery. Braga and
Gianotti13 and Braga et al.1 used hospital costs data gathered from
GI cancer surgical patients included in a randomized controlled
trial performed in an Italian hospital setting. Both analyses
concluded that IMF was an effective and cost-saving nutritional
therapy. These results confirmed a previous study using German
cost data.12 Furthermore, Mauskopf et al.14 estimated the impact of
IMF on US hospital costs. Although they showed that IMF was cost-
saving compared to SoC in GI cancer surgery, they did not focus on
incremental costs due to complications. Our study is limited by the
fact that hospitalization costs were not collected by micro-costing
method or alongside clinical trials, which might reduce its accu-
racy. Nevertheless, our results are comparable to the ones of Sen-
kal12 and Braga,1 who both used more detailed micro-costing
methods to compute complications costs. In both studies, costs of
IMF for all patients were offset by the savings due to the decrease in
complication rates. In addition, our approach of taking into account
exogenous severity score of the patients allowed for isolating the
hospital costs attributed to the complications partially preventable
by the use of IMF. Despite the lack of micro-costing hospital cost
data, our approach allowed to compute the hospital costs for
treating complications partly preventable with IMF. Thus correcting
for case’s severity into DRG hospital database can be an option to
identify hospital costs attributable to specific diseases, in-
terventions or comorbidities.
Our analysis used the clinical outcomes from the meta-analysis
of Cerantola and coauthors which mixed different IMF formulas.5
Therefore, a comparison between the different IMF formulas
could be of interest as well. However, Drover and coauthors have
already done this comparison and demonstrated that the IMF
Fig. 3. Estimated cost-savings depending on the initial complications rate in the
control group (post-operative regimen). Vertical axe’s title: Savings per patient’s stay
in Swiss francs. Horizontal axe’s title: Baseline complication rate.
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653
containing arginine, omega-3 fatty acids and nucleotide had the
strongest efficacy on risk of infections and hospital LOS.6
IMF containing arginine, fish oil and nucleotides has been
constantly demonstrating its efficacy when taken accordingly to
recommended intake in well-nourished and malnourished GI
cancer patients undergoing surgery; and has received a grade A
recommendation into ESPEN Guidelines on Enteral Nutrition for
Surgery including organ transplantation.15 The clinical benefit of
IMF has been shown on decreasing risk of overall complications,
infectious complications and LOS. However, the role of IMF on
prevention of infections with multi-resistant strains has not been
demonstrated. This lack of data is probably related to the fact that
infections caused by multi-resistant strains have gained clinical
importance only during recent years.
In almost all Western countries, healthcare costs are rapidly
increasing and the increasing gap between costs and available re-
sources has become a serious issue,17 especially during economic
downturns. The development and implementation of effective cost
containment measures represent an ongoing major challenge
involving all players in the healthcare market. Pre-operative
assessment of surgical risk and interventions aiming at decreasing
the post-operative complications and infections risk are the two
potentially successful approaches. Among pre-operative surgical
risk, malnutrition is a well-known risk factor for all kind of post-
operative complications. In post-operative period, malnourished
patients are indeed more vulnerable to infection and present
delayed wound healing.18,19 Therefore screening for malnutrition
risk and intervening with medical nutrition are two assets in pre-
venting and fighting hospital-acquired infection, especially in a
context of increasing bacteria resistance. In addition, IMF nutri-
tional intervention in well-nourished patients has also been
demonstrated to be an asset in decreasing the risk of post-operative
complications.3e7,11 Hence independently of the nutritional status,
this study and the previous available cost-effectiveness analyses
and meta-analyses of RCTs on IMF have demonstrated that
immune-modulating nutritional intervention when taken accord-
ingly to recommendations is also an asset to support patients’ re-
covery after GI cancer surgery.
By decreasing the risk of complications by 27%e48%, IMF could
allow hospitals to make net savings ranging between CHF 1638 and
2488 per patients. Therefore, IMF can be considered as a dominant
intervention in GI cancer patients undergoing elective surgery: it is
a more effective and a cost-saving nutritional intervention
compared to nil-by-mouth or standard enteral nutrition. As IMF is a
very simple intervention in an era of high technology, it should be
recommended to hospitals willing to decrease infectious compli-
cations as well as to control hospital costs.
Conflict of interest
Since the initiation of this publication, JBW, ND and MS have
been invited from time to time by Nestlé Health Science to present
into symposium on topics realted to medical nutrition and/or into
experts panel.
Acknowledgment
Funding: HCS works for Nestlé Health Science, as Global Head of
the Health Economics. CP and JBW were consultants for Nestlé
Health Science for this study. YC, MS and ND didn’t receive any
financial incentive or support to collaborate to the study.
Authors’ contribution: HCS initiated the project and wrote the
abstract and manuscript. CP realized the DRG cost database analysis
and reviewed the manuscript. YC computed the relative risk of
infectious and non-infectious complications based on the same
654 H. Chevrou-Séverac et al. / Clinical Nutrition 33 (2014) 649e654
data has the Cerantola et al. (2011) meta-analysis. MS and YC
brought their medical expertise to carefully select the cost data for
patients matching their meta-analysis (i.e. GI cancer patients un-
dergoing major GI surgery). CP, YC, MS, JBW and ND actively
reviewed and contributed to the abstract and manuscript.
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