EAL

ONC: Pancreatic Cancer (2006)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To determine the effects of the administration of a nutritional supplement containing fish oil on the levels of acute phase proteins in patients with advanced pancreatic cancer.

Inclusion Criteria:

Advanced pancreatic cancer
Weight loss (duration and type not specified)
Three weeks post surgery or bile duct stenting

Exclusion Criteria:

Not Specified

Description of Study Protocol:

Recruitment Not Described

Design Advanced pancreatic cancer patients post surgery or bile duct stenting were enrolled. At least 3 weeks post surgery the following was collected:

Weight (without shoes; using a beam scale)
Venous blood sampling of the following:
- C reactive protein
- Alpha 1 antitrypsin
- Alpha 1 acid glycoprotein
- Haptoglobin
- Ceruloplasmin
- Albumin
- Prealbumin
- Transferrin
- Fibrinogen (Baseline only)

The initial 18 patients received full supportive care (not described). Blood was sampled again at median day 28.

The subsequent 18 patients received 2 cans per day of a fish oil enriched liquid nutritional supplement (Per can: 310 Kcal, 16g protein, 1.09g EPA, 0.46g DHA, 240mL) for a four week period. Blood was sampled again at median day 24.

Six healthy individuals were used as controls.

Blinding used (if applicable) Not applicable

Intervention (if applicable) An initial 18 patients with advanced pancreatic cancer received full supportive care alone and underwent blood sampling at baseline and 28 days. A subsequent 18 patients with advanced pancreatic cancer received 2 cans per day of a fish oil enriched liquid nutritional supplement and underwent blood sampling at baseline and day 24. Six health volunteers were used as a comparison group.

Statistical Analysis Analyses included:

Descriptive statistics (median, Interquartile range)
Mann-Whitney U test
Wilcoxon signed rank test
Chi square test
p< 0.05

Data Collection Summary:

Timing of Measurements At least 3 weeks post surgery the following was collected:

Weight (without shoes; using a beam scale)
Venous blood sampling of the following:
- C reactive protein (CRP)
- Alpha 1 antitrypsin
- Alpha 1 acid glycoprotein
- Haptoglobin
- Ceruloplasmin
- Albumin
- Prealbumin
- Transferrin
- Fibrinogen (Baseline only)

Non-supplemented Group: tests were repeated at a median 28 days, with the exception of fibrinogen, which was not repeated

Supplemented Group: these tests, excluding fibrinogen, were repeated at a median 24 days.

Healthy Controls: Not described

Dependent Variables

Variable 1: Positive acute phase protein reaction as measured with C reactive protein, Alpha 1 antitrypsin, Alpha 1 acid glycoprotein, Haptoglobin, Ceruloplasmin, Fibrinogen
Variable 2: Negative acute phase protein reaction as measured with Albumin, Prealbumin, Transferrin
Variable 3: Nutrition status as measured by weight

Independent Variables

Presence of advanced pancreatic cancer
Intake of fish oil supplemented liquid nutritional supplement

Description of Actual Data Sample:

Initial N: 42 [6 Healthy Controls; 36 Advanced pancreatic cancer patients] Sex not described

Attrition (final N): 42 [6 Healthy Controls; 36 Advanced pancreatic cancer patients] Sex not described

Age: 54y (50-56y) Healthy Controls;

60y (54-70y) Non-Supplemented group;

64y (56-66y) Supplemented group

Ethnicity: Not described

Other relevant demographics:

UICC Stage of Disease

Group     Stage 2   Stage 3 Stage 4

Supplemented 10 2 6

Non-Supplemented 8 2 8

Baseline Serum Acute Phase Protein Levels in Cancer Patients

Variables

Supplemented Group

Non-Supplemented Group

Statistical Significance of Group Difference

Positive acute phase protein reaction

     C Reactive Protein <5 (<5-21) 11 (<5-30) NS

     a1 antitrypsin 2.07 (1.62-2.33) 2.22 (1.76-2.73) NS

     a1 acid glycoprotein 1.12 (0.89-1.39)   1.33 (0.94-2.10) NS

     Haptoglobin 2.01 (1.45-2.21)
2.26 (1.75-2.63)
NS

     Ceruloplasmin 0.30 (0.27-0.35) 0.38 (0.32-0.44) 0.035

Negative acute phase protein reaction

     Albumin 41 (38-43) 41 (35-44) NS

     Prealbumin 0.20 (0.14-0.22) 0.22 (0.13-0.30) NS

     Transferrin 2.17 (1.89-2.61) 2.38 (2.01-2.75 NS

Ceruloplasim significantly higher in non-supplemented group

Anthropometrics

Percentage Pre-study Weight Loss

Group Prestudy Weight Loss

Supplemented 11.8% (5.6-23.5)

Non-Supplemented 17.9% (15.9-20.7)

Location

: Royal Infirmary of Edinburgh, Edinburgh, UK

UICC Stage of Disease
Group	Stage 2	Stage 3	Stage 4
Supplemented	10	2	6
Non-Supplemented	8	2	8

Percentage Pre-study Weight Loss
Group	Prestudy Weight Loss
Supplemented	11.8% (5.6-23.5)
Non-Supplemented	17.9% (15.9-20.7)

Summary of Results:

Healthy Controls versus Cancer Patients:

Serum concentrations of negative acute phase proteins (albumin, prealbumin, and transferrin) were significantly lower (p< 0.04) in cancer patients than in healthy controls. Serum concentrations of positive acute phase proteins (CRP, fibrinogen, a1 antitrypsin, a1 acid-glycoprotein, haptoglobin, ceruloplasmin) were significantly higher (p< 0.04) in cancer patients.

Effect of Supplementation on Acute Phase Protein Levels and Weight in Cancer Patients:

**Changes in Acute Phase Protein Concentrations and Weight Over a 4 Week Period**
	Supplemented Group	Non-Supplemented Group	Statistical Significance of Group Difference
Change in Total Positive Acute Phase Protein Level¹	-0.02g/L (-0.19 - +0.53)	+0.42g/L (-0.30 - +1.24)	NS
Change in Total Negative Acute Phase Protein Level²	+1.32 g/L (-1.07 - +2.95)	-2.44g/L (-5.72 - +0.28)	0.0012
Weight	+1.0 Kg (-0.1- +2.0)	-2.82²Kg (-3.7- -1.7)	0.0001

Positive Acute Phase Proteins: C reactive protein, Alpha 1 antitrypsin, Alpha 1 acid glycoprotein, Haptoglobin, Ceruloplasmin
Negative Acute Phase Proteins: Albumin, Prealbumin, Transferrin

Supplemented Group:
- Significant increase in transferrin (p = 0.031)
- Significant increase in total negative acute phase protein production (p=0.0048)
- No significant changes from baseline in C reactive protein, Alpha 1 antitrypsin, Alpha 1 acid glycoprotein, Haptoglobin, Ceruloplasmin, Albumin, Prealbumin
Non-Supplemented Group:
- Significant increase in C reactive protein (p=0.0013)
- Significant decrease in albumin (p=0.012), prealbumin (p=0.0048) , and transferrin (p=0.0038)
- Significant decrease in total negative acute phase protein production (p=0.0016)
Between Group Comparisons
- Significant difference (p=0.0012) in total negative acute phase proteins between groups at 4 weeks
- Significant difference in weight change at four weeks of intervention, with the supplemented group experiencing a mean increase in weight [+1.0 Kg (-0.1- +2.0Kg)]and the non-supplemented group experiencing a decrease in weight [-2.82Kg (-3.7- -1.7Kg)]

Author Conclusion:

Patients with advanced pancreatic cancer exhibit the typical acute phase protein response seen in other tumor groups with increased positive acute phase proteins and decreased negative acute phase proteins.

Supplementation with a fish oil containing liquid nutritional supplement for 4 weeks led to increased weight and transferrin. The fish oil may be causing a combination of the attenuation of the acute phase protein response and improvement in nutritional status. Additional work is needed to elucidate the mechanism of action of fish oil in advanced cancer patients.

Funding Source:

Reviewer Comments:

No information provided on:

Funding source
Conflict of interest
Ethnicity
Cancer treatment
Exclusion cirteria
Compliance with therapy
Dietary intake
Description of "full supportive care"

Limited information on:

Inclusion criteria
Duration of supplementation
Location of study (inpatient versus outpatient)

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?	No
2.	Was the selection of study subjects/patients free from bias?		No
	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?	No
	2.2.	Were criteria applied equally to all study groups?	No
	2.3.	Were health, demographics, and other characteristics of subjects described?	No
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
3.	Were study groups comparable?		No
	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?	No
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	No
	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?	No
	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.)	???
	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?	No
	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.)	No
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	No
	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?		No
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	No
	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?	No
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	No
	6.6.	Were extra or unplanned treatments described?	No
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	N/A
	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?	No
	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?		No
	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)?	No
	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?	No
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	No
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

Variables	Supplemented Group	Non-Supplemented Group	Statistical Significance of Group Difference
Positive acute phase protein reaction
C Reactive Protein	<5 (<5-21)	11 (<5-30)	NS
a1 antitrypsin	2.07 (1.62-2.33)	2.22 (1.76-2.73)	NS
a1 acid glycoprotein	1.12 (0.89-1.39)	1.33 (0.94-2.10)	NS
Haptoglobin	2.01 (1.45-2.21)	2.26 (1.75-2.63)	NS
Ceruloplasmin	0.30 (0.27-0.35)	0.38 (0.32-0.44)	0.035
Negative acute phase protein reaction
Albumin	41 (38-43)	41 (35-44)	NS
Prealbumin	0.20 (0.14-0.22)	0.22 (0.13-0.30)	NS
Transferrin	2.17 (1.89-2.61)	2.38 (2.01-2.75	NS