EAL

ONC: Surgery (2006-2007)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To investigate the impact of an omega three fatty acid (n-3FA ) supplemented diet versus an arginine (ARG) supplemented diet in post-surgical oral and laryngeal cancer patients on nutrition variables, clinical outcome, postoperative infections, and wound complications.

Inclusion Criteria:

Post-surgical oral and laryngeal cancer patients
No recent weight loss (< 5% at 3 months prior to study)
Ambulatory

Exclusion Criteria:

Severely impaired hepatic function (t-bilirubin > 3.5 mg/dL)
Severely impaired renal function (creatinine > 2.5 mg/dL)
Ongoing infection
Fever in the preceeding month
Major gastrointestinal disease
Autoimmune disorders
Steroid treatment
Medication which could modulate metabolism and/or weight

Description of Study Protocol:

Recruitment Subjects were recruited at time of hospital discharge post surgery.

Design

Subjects were enrolled and randomized using sealed envelopes at time of discharge.
Subjects were asked to consume either 2 cans of a n-3FA supplemented liquid nutritional supplement or 2 cans of a ARG supplemented liquid nutritional supplement for 12 weeks in addition to an oral diet of 30 Kcal/kg/day and 1.1 g protein/kg/day.
Subjects were also instructed to complete regular physical activity (1 hour of walking per day).

Nutritional Composition of Liquid Nutritional Supplements
Nutrient	n-3 FA Supplement (Group 1)	ARG Supplement (Group 2)
Volume	240 ml	300 ml
Total Energy	295 Kcal	303 Kcal
Protein:
Total	15.96g	16.7g
Free L-Agrinine	-	3.7g
Lipid:
Total	6.14g	8.3g
EPA	1.01g	0.59g
DHA	0.31g	0.37g
Carbohydrate	43.99g	40.2g
Dietary Fiber	2.64g	3g

Subjects completed 3 day food diaries at baseline (week 0) and week 12, which included 1 weekend day and 2 week days. Total energy and macronutrient intakes were calculated fromthis data. Alcohol intake and smoking habits were also measured.

Blinding used: Unclear. Patients were randomized using sealed envelopes but no other indication of blinding was reported.

Intervention: Subjects were randomized using sealed envelopes to consume, in addition to oral diet, either 2 cans of an n-3FA enriched liquid nutritional supplement (1.32 g n-3FA/can) or 2 cans of an ARG containing liquid nutritional supplement (3.7g ARG/can)

Statistical Analysis The intent to treat analyses included:

Frequencies
Kolmogorov-Smirnov test (distribution of variables)
2 tailed-paired or unpaired t-test
ANOVA
Freidman or Wilcoxon test
p< 0.05

Power calculation indicated 30 patients were necessary to detect an improvement of 5 kg with a p value <0.05 and power of 80%

Data Collection Summary:

Timing of Measurements

The following studies were completed at baseline (time of hospital discharge) and week 12:

Physical examination
Height
Weight
Body mass index (kg/m²)
Regional changes in body mass as measured by muscle circumferences and tricep skinfold measurement
Body composition as measured with bioelectrical impedance analysis (BIA)
Posoperative complications (none, general infections, urinary tract infections, local, wound infections)
Gastrointestinal symptoms
Biochemical Indices
- Albumin
- Prealbumin
- Transferrin
- Lymphocytes
3 day food diary (instructed by RD on how to record intake)

Patients were also asked to keep a record of partial or whole can consumption of supplement.

Dependent Variables

Variable 1: Nutrition Variables as measured by anthropometrics (height, weight, BMI, BIA, skinfold assessments), GI symptoms, biochemical indices (albumin , prealbumin , transferrin , lymphocytes), and food diary
Variable 2: Clinical Outcome as measured by presence of post-operative complications
Variable 3: Postoperative infections as measured by presence or absence
Variable 4: Wound complications as measured by presence or absence

Independent Variables Intake of of n-3FA or ARG supplemented liquid nutritional supplements

Description of Actual Data Sample:

Initial N: 73 [38 (36 male, 2 female) n-3FA group; 35 (32 male, 3 female) ARG group]

Attrition (final N): 73 [38 (36 male, 2 female) n-3FA group; 35 (32 male, 3 female) ARG group]

Age: 60.2 ± 11.15 years n-3FA group; 62.5 ± 11.4 years ARG group

Ethnicity: Not specified

Other relevant demographics:

Patient Demographic Variables

Variable n-3FA Group ARG Group

Smoking Habit 11.4%     13.2%

Alcohol Habit 17.2% 21.1%

Disease Stage

    I 0 0

    II 8 4

    III     10 9

    IV 20 22

Diagnosis

    Oral Cavity 9 8

    Larynx 29 27

No significant differences between groups.

Anthropometrics

Patient Demographic Variables
Variable	n-3FA Group	ARG Group
Body Weight	65.5 ± 11.5 kg	68.2 ± 10.8 kg
Body Mass Index	23.81 ± 3.7 kg	24.6 ± 3.3 kg
Fat Free Mass	53.1 ± 8.7 kg	52.1 ± 8 kg
Fat Mass	15.4 ± 6.6 kg	16.7 ± 5.7 kg
Tricep Skinfold	10.9 ± 4.7 mm	11.3 ± 5.4 mm
Arm Circumference	27.4 ± 3.4 cm	27.4 ± 2.8 cm

Location: Hospital Rio Hortega and Hospital Clinico, Valladolid, Spain

Summary of Results:

Variables	n-3FA Group Measures and confidence intervals	ARG group Measures and confidence intervals	Statistical Significance of Group Difference
Nutrition Variables
Albumin, g/dL
Basal	3.12 ± 0.9	3.01 ± 0.57	NS
3 Months	4.26 ± 0.76*	4.12 ± 0.81*	NS
Prealbumin, mg/dL
Basal	20.7 ± 7.1	21.8 ± 7.1	NS
3 Months	27.2 ± 5.7*	25.36 ±6.8*	NS
Transferrin, mg/dL
Basal	184.4 ± 41.1	177.7 ± 38.9	NS
3 Months	245.39 ± 44.4*	231.9 ± 59.2*	NS
Lymphocytes, 10³ micro L/mm³
Basal	1,538 ± 454	1,596 ± 568	NS
3 Months	2,090 ± 1,158*	2,270 ± 841*	NS
Weight, kg
Basal	65.5 ± 11.5	68.2 ± 10	NS
3 Months	70.4 ± 11.1*	69.1 ± 11.4	NS
Fat Free Mass, kg
Basal	53.1 ± 8.7	52.1 ± 8	NS
3 Months	52.1 ± 8.6	52.9 ± 8.4	NS
Fat Mass, kg
Basal	15.4 ± 6.6	16.7 ± 5.7	NS
3 Months	18.1 ± 8.4*	16.4 ± 6.5	NS
Triceps Skinfold, mm
Basal	10.9 ± 4.7	11.3 ± 5.4	NS
3 Months	12.35 ± 6.1*	11.4 ± 4.5	NS
Arm Circumference, cm
Basal	27.4 ± 3.4	27.4 ± 2.8	NS
3 Months	27.7 ± 4.4	27.7 ± 3.3	NS

* = Basal vs. 3 month values p< 0.05

Nutrition Variables

Duration of Supplementation:

n-3FA Group: 86.3 ± 26 days
ARG Group: 90 ± 22.6 days
Non-significant difference

Volume of Supplement Consumed:

n-3FA Group: 1.5 ± 0.52 units
ARG Group: 1.5 ± 0.52 units
Non-significant difference

Total Calorie Consumption:

n-3FA Group: 2,034 ± 501 Kcal/day
ARG Group: 1,948 ± 607 Kcal/day
Non-significant difference

Total Protein Consumption:

n-3FA Group: 95.68 ± 40.4 g/day
ARG Group: 94.1 ± 28 g/day
Non-significant difference

Gastrointestinal Intolerance:

n-3FA Group: 0 incidences
ARG Group: 0 incidences

Biochemical Indices:

Significant in-group improvement at 3 months in ARG and n-3FA group in all biochemical indices
No significant difference between groups

Anthropometric Parameters:

Significant increase in weight, fat mass, and triceps skinfold at 3 months in n-3FA group only
No significant difference between groups

Infections Complications

n-3FA Group: 0% (n=0)
ARG Group: 8.57% (n=3)
Non-significant difference

Other Findings

Alcohol and smoking habits did not affect results

Author Conclusion:

Outpatient ambulatory supplementation of oral diet with ARG enriched liquid nutritional supplements does not improve weight or indices of body composition after 3 months of supplementation. Significant improvements were seen in serum protein levels. Further studies are warranted to examine the potential role of ARG enriched supplements in an outpatient setting.

Funding Source:

Reviewer Comments:

This study appears to be well designed and well written. Overall oral intake and supplement compliance was good and similar to that presented in other studies of immune enhanced liquid nutritional supplements:

Limitations:

No information provided on funding source

Subjects were only included if they had lost less than 5% of their body weight over the past 3 months, this is not always characteristic of head and neck patients.

No control supplement which did not contain immune-enhancing ingredient to assess the effect of non-supplemented liquid nutritional supplements on weight.

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?	No
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)	Yes
	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?		Yes
	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?		???
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	???
	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?	N/A
	6.6.	Were extra or unplanned treatments described?	N/A
	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)?	Yes
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	Yes
	8.6.	Was clinical significance as well as statistical significance reported?	No
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	Yes
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?		???
	10.1.	Were sources of funding and investigators' affiliations described?	No
	10.2.	Was the study free from apparent conflict of interest?	Yes