Gastroenterology

Gastroenterology

Volume 138, Issue 4, April 2010, Pages 1312-1320
Gastroenterology

Clinical—Alimentary Tract
Effects of Ghrelin Administration After Total Gastrectomy: A Prospective, Randomized, Placebo-Controlled Phase II Study

https://doi.org/10.1053/j.gastro.2009.12.058Get rights and content

Background & Aims

Body weight (BW) loss and reduction of blood ghrelin level are commonly observed after total gastrectomy (TG). A prospective study was designed to elucidate whether exogenous ghrelin administration prevents postoperative BW loss by improving appetite and oral food intake in patients with gastric cancer after undergoing TG.

Methods

In this randomized phase II study, 21 patients undergoing TG were assigned to a ghrelin (11 patients) or placebo group (10 patients). They received intravenous infusion of synthetic human ghrelin (3 μg/kg) or saline twice daily for 10 days after starting oral food intake following surgery. Changes in BW, appetite visual analog scale score, food intake calories, body composition, basal metabolic rate, and various blood test results were evaluated.

Results

Excluding one patient who developed profound diaphoresis during ghrelin infusion, 20 patients completed the study. Food intake and appetite were significantly higher with ghrelin compared with placebo (average, 13.8 vs 10.4 kcal/kg/day [P = .030] and 5.7 vs 3.9 cm [P = .032], respectively). BW loss was significantly lower in the ghrelin than in the placebo group (−1.4% vs −3.7%; P = .044). Fat mass, lean body mass, and basal metabolic rate decreased significantly in the placebo group; however, the reductions in lean body mass and basal metabolic rate were not significant in the ghrelin group, although that of fat mass was significant.

Conclusions

Short-term administration of synthetic ghrelin was safe and successfully lessened postoperative BW loss and improved appetite and food intake after TG.

Section snippets

Patients

Twenty-one patients who underwent total gastrectomy at Osaka University Hospital between June 2006 and June 2008 were enrolled in the study. The inclusion criteria were as follows: (1) adenocarcinoma of the stomach confirmed by histopathologic examination, (2) preoperative clinical staging with less than stage II (International Union Against Cancer TNM stage classification), (3) curative surgical treatment (R0) (ie, total gastrectomy with D1 or D2 lymph node dissection), and (4) age between 20

Patient Characteristics

The study flow diagram is summarized in Figure 1B. One of the 11 patients (9.1%) in the ghrelin group developed profuse diaphoresis during ghrelin infusion, equivalent to grade 1 by National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Accordingly, we decided to stop ghrelin administration and the patient was excluded from further analysis. The 10-day course of ghrelin administration was well tolerated by the remaining 10 patients without any adverse events,

Discussion

Body weight loss is a common finding in patients who undergo gastrectomy for gastric cancer, which not only associates with various pathologic conditions but also affects patients' social activity. Therefore, postoperative body weight loss needs to be investigated thoroughly, especially in Japan, where early gastric cancer accounts for more than 50% of the total incidence of gastric cancer,30 and the 5-year survival rate of early gastric cancer is more than 90%.31 Previous studies reported that

Acknowledgments

Online registry: http://www.umin.ac.jp; clinical trial no. UMIN000001925.

The authors thank Tomoyuki Sugimoto from the Department of Biomedical Statistics, Osaka University, for the advice on statistical analysis as well as the nutritional management room staff of Osaka University Hospital for calculating food intake calories per day in this study.

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    Conflicts of interest The authors disclose no conflicts.

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