EAL

ONC: Branched Chain Amino Acids (2006)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To clarify whether or not long-term oral administration of BCAAs is effective in terms of clinical features, laboratory data, cancer recurrence and overall survival in patients undergoing hepatic resection for primary HCC

Inclusion Criteria:

Patients who had undergone possibly curative hepatic resection for primary hepatocellular carcinoma

Exclusion Criteria:

non-curative resection

inability to participate in the study soon after randomization because of complications or referral to distant hospitals

non-compliance

Description of Study Protocol:

Recruitment

150 patients who had undergone possibly curative hepatic resection for primary hepatocellular carcinoma were recruited.

Design

150 patients were randomized 2-3 weeks after surgery

Control group - ate their usual meals

BCAA group - ate their usual meals; drank 50 g Aminoleban EN twice a day in the morning and in the evening for at least 1 year.

Blinding used (if applicable)

Not specified.

Intervention (if applicable)

50 g Aminoleban EN twice a day in the morning and in the evening for at least 1 year

Compositition of Aminoleban EN: per 100 grams: 27.0 g protein (13.0 g peptides, 13 g amino acids, 1.0 g casein), 62.1 g dextrin and 7.0 g rice oil. yields: 420 kcal

Statistical Analysis

Data analyzed by the chi² test, Mann-Whitney U test, or unpaired Students' t test.

Changes in clinical features: compared by Kolmogorov-Smirnov test.

Cumulative survival and intrahepatic recurrence rates: Kaplan-Meier method

P values less than 0.05 were considered statistically significant

Data Collection Summary:

Timing of Measurements

After discharge from hospital, patients were followed up monthly for one year and every few months thereafter. Clinical features and biochemical parameters were measured at monthly intervals. Tumor recurrence was studied at 3-month intervals.

Dependent Variables

Clinical features - flapping tremor, encephalopathy, ascites, edema, performance status
Red cell and platelet counts
Hepatic function - AST, ALT, Bilirubin, albumin, cholesterol, ammonia

Independent Variables

50 g Aminoleban EN twice a day in the morning and in the evening for at least 1 year

Description of Actual Data Sample:

Initial N: 109 males, 23 females

Attrition (final N): 43; 34 patients in BCAA group and 32 patients in the control group had died by the time of final follow-up. Causes: cancer recurrence, liver failure, subarachnoid hemorrhage. Overall cumulative survival rates were no different between groups.

Age: 12 patients < 50 years; 100 patients 50-70 years; 20 patients > 70 years

Ethnicity: unknown

Anthropometrics / demographics: two groups were comparable in terms of age, sex, alcohol abuse, underlying liver disease, Child grade, tumor size, tumor node metastasis stage, and extent of liver resection.

Location: not specified

Summary of Results:

Compliance and side-effects of BCAA treatment:

63 of 67 patients continued to take BCAA for at least 1 year; treatment stopped due to side effects in 3 and tumor recurrence in 1.

Clinical effect of branched chain amino acid treatment:

the rates of flapping tremor and performance status =/< 70 were higher in the control group

Ascites and edema were significantly less common in the BCAA group but only within the first 3 months

Body weight was greater in the treatment group at all time points in the first year

Effect of BCAA treatment on red cell and platelet counts:

Trend toward higher red blood cell and platet counts in the BCAA group

Effect of branched chain amino acid treatment on hepatic function:

No significant differences in conventional liver tests between the two groups

Intrahepatic recurrence:

39 patients total: 58% in BCAA group vs 60% in control group

Author Conclusion:

"It is concluded that long-term oral supplementation with BCAAs after curative resection of HCC is beneficial in improving body-weight, performance status, and neurological conditions as well as red cell and platelet counts, serum albumin level and amino acid patterns without increasing the rate of tumor recurrence after major hepatic resection."

Additional author comments:

Of concern with nutritional support to patients with malignant disease is the potential for stimulating tumor growth
With the present study, follow-up of these patients showed that tumour recurrence and overall patient survival rates were not influenced by the BCAA treatment

Funding Source:

University/Hospital:

Shimane Medical University (Japan)

Reviewer Comments:

Overall, the framework of this study solid. However, the study begins to fall short in the description of the methods. It is unknown through reading the study whether blinding of any sort was used, how compliance of the BCAA formula was determined, if there was funding from outside sources that may bias results, and what the ethnicity of the patients was. Without some of these important details, it is difficult to state whether or not this is a credible study.

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?	???
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?	Yes
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)	???
	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%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	Yes
	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?	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?	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)?	Yes
	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?		???
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	No
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?	???