EAL

ONC: Nutrition Status and Outcomes in Adult Oncology Patients (2013)

Citation:

Braga M, Gianotti L, Vignali A, Cestari A, Bisagni P, Di Carlo V. Artificial nutrition after major abdominal surgery: Impact of route of administration and composition of the diet. Crit Care Med.1998; 26(1): 24-30.

PubMed ID: 9428539

Study Design:

Randomized Controlled Trial

Class:

A - Click here for explanation of classification scheme.

Quality Rating:

POSITIVE: See Quality Criteria Checklist below.

Research Purpose:

To evaluate the impact of the route of administration of artificial nutrition and the composition of the diet on outcome after major abdominal surgery in gastric and pancreatic cancer patients.

Inclusion Criteria:

Adult patients with histologically documented gastric or pancreatic cancer, candidates for elective curative surgery
Patients who signed a written informed consent.

Exclusion Criteria:

Clinically relevant alteration of renal, hepatic, cardiac or gastrointestinal function
Ongoing infections
History of immune disorders.

Description of Study Protocol:

Recruitment

Patients who met the inclusion criteria were prospectively enrolled at the study institution.

Design

Randomized clinical trial.

Blinding used

Post-operative infections were recorded by members of the surgical staff who were not involved in the study.

Intervention

At surgery, patients were randomly assigned to three groups:
- Enriched group (received an enteral diet supplemented with arginine, RNA and omega-3 fatty acids)
- Control group (received an isocaloric, isonitrogenous standard enteral formula)
- TPN group (received an isocaloric, isonitrogenous total parenteral nutrition)
The infusion of the enteral diets started within 12 hours after surgery. The rate was progressively increased to the daily nutritional goal (25kcal per kg, 0.25g of nitrogen per kg) that was reached on post-operative day (POD) four.
To achieve an isocaloric and isonitrogenous treatment in all groups, enteral feeding was integrated with parenteral nutrition until POD four. Nutrition support was continued for seven days after surgery.
Oral food intake was allowed on POD eight. The patients unable to resume oral feeding on POD eight continued the nutrition support according to the protocol. Outcome measures were recorded during the study period and evaluated using statistical analysis.

Statistical Analysis

The means of continuous variables were compared by one-way analysis of variance. If an overall significant difference was found among the three groups, then Tukey's test was used to evaluate which group was different from the other.
The statistical analysis among discrete parameters was performed by chi-square test
P<0.05 was considered statistically significant.

Data Collection Summary:

Timing of Measurements

Amount of enteral or parenteral nutrition recorded daily. Post-operative duration of artificial nutrition was recorded for all subjects.
Possible adverse effects to enteral nutrition were recorded daily. The first bowel movement was also recorded.
Post-operative infections and non-infectious complications were recorded as they occurred.

Dependent Variables

Side effects of early enteral feeding (abdominal distention, abdominal cramps, diarrhea, emesis, displacement of jejunostomy)
Non-infectious post-operative complications (cardiopulmonary, pancreatic fistula, dehiscence of digestive anastomosis, pancreatic or biliary fistula)
Post-operative infections (wound infection, unknown fever, abdominal abscess, pneumonia, over-infection of pancreatic or biliary fistula, urinary tract infection)
Severity of infection (evaluated according to the Sepsis Score) and the length of post-operative stay (LOS).

Independent Variables

Route of administration (enteral vs. parenteral)
Composition of diet (standard enteral formula, enriched enteral formula and TPN).

Control Variables

Age
Baseline hemoglobin and albumin
Pre-operative weight loss
Homologous transfusion
Surgical procedures (gastrectomy vs. pancreatoduodenectomy)
Duration of surgery
Operative blood loss.

Description of Actual Data Sample:

Initial N: 166 patients with gastric (N=92) or pancreatic (N=74) cancer (90 males, 72 females)
Attrition (final N): 166
Age: Mean age 623±9.2 years
Anthropometrics: No significant difference with respect to age, hemoglobin and albumin values, weight loss, type and duration of surgery, operative blood loss, or rate of homologous transfusion among the three groups
Location: Department of Surgery, Scientific Institute San Raffaele, University of Milan, Italy.

Summary of Results:

Key Findings

25 (22.7%) of 110 patients who received enteral nutrition complained of adverse effects. Only seven (6.3%) did not reach nutritional goal
The enteral-fed patients had a significantly quicker canalization to gas and stools than patients fed parenterally (P<0.05)
Early enteral nutrition did not increase the rate of anastomotic dehiscences and pancreatic or biliary fistula. Cardiopulmonary complications in the TPN group were double those in the two enteral groups.
34 (20.4%) patients developed post-operative infections. The post-operative infection rate was highest in the TPN group and lowest in the enriched group. The enriched group had a significantly lower Sepsis Score than the TPN group.

Post-operative

Infections

Enriched

(N=55)

Control

(N=55)

TPN

(N=56)

Statistical Significance

of Group Difference

(Enriched vs. TPN)

Total

9 (16.3%)

13 (23.6%)

16 (28.5%)

P=0.1

Sepsis Score

4.0±1.6

6.5±3.0

8.6±4.5

P<0.05

78 (47%) patients were classified as malnourished before operation (defined as a pre-operative weight loss more than 10% in the previous six-month period) and 42 (25.3%) were given homologous transfusions during the peri-operative period. The post-operative infection rate was higher in these two sub-groups.

Post-operative

Infections

Enriched

(N=55)

Control

(N=55)

TPN

(N=56)

Malnourished sub-group

16.0%

25.9%

30.7%

Transfused sub-group

20.0%

38.4%

42.8%

In both the malnourished and the transfused sub-groups, both severity of post-operative infections and length of post-operative stay were significantly reduced in the enriched group compared with the TPN group (P<0.05)
In transfused patients, the rate of septic complications was 20.0% in the enriched group, 38.4% in the control group and 42.8% in the TPN group.

Author Conclusion:

Data from this study show that early post-operative enteral infusion of nutrients, even when proximal to a "fresh" gastrointestinal anastomosis, is safe and well tolerated and stimulates an early return of bowel function
Although this study shows that early enteral feeding with a standard diet exerts only a slight improvement of clinical outcome compared with TPN, the lower cost, the safety and the good tolerance should encourage the routine use of jejunal infusion of nutrients after major surgery
Besides the route of administration, the composition of diet also exerts a progressive effect with the enriched formula giving the best results and the TPN the worst
In conclusion, early enteral feeding is a suitable alternative to TPN after major abdominal surgery. The use of the enriched diet appears to be more beneficial in malnourished and transfused patients.

Funding Source:

University/Hospital:	University of Milan, Italy / University hospital
In-Kind support reported by Industry:	Yes

Reviewer Comments:

Besides post-operative infections, unclear if other measures were recorded by staff who were blinded. Due to study design, route of administration unable to be blinded but composition of diet could have been blinded.
90 males and 72 females do not add up to a total of 166 patients
It was assumed that all outcome variables were measured only during the seven-day post-operative duration and longer for patients unable to resume oral feeding on POD eight
The enteral diets were provided by Novartis Nutrition but unclear if industry contributed any other funding to the study itself.

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		Yes
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
3.	Were study groups comparable?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	No
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		N/A
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	N/A
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	N/A
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		No
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	No
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	???
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	Yes
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	N/A
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	No
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	???
	10.2.	Was the study free from apparent conflict of interest?	Yes