Ghrelin Level and Body Weight Loss After Esophagectomy for Esophageal Cancer

Miyazaki, Tatsuya; Tanaka, Naritaka; Hirai, Hanako; Yokobori, Takehiko; Sano, Akihiko; Sakai, Makoto; Inose, Takanori; Sohda, Makoto; Nakajima, Masahiro; Fukuchi, Minoru; Kato, Hiroyuki; Kuwano, Hiroyuki

doi:10.1016/j.jss.2011.09.016

Cited by 23 publications

(13 citation statements)

References 28 publications

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“…; Table S2 , supporting information), and fasting ghrelin levels were unrelated to weight loss. This is consistent with cross‐sectional data indicating normalization of fasting ghrelin concentrations among patients in the long term after oesophagectomy, and with rodent studies demonstrating increased production of ghrelin from extragastric sites after gastrectomy.…”

Section: Discussionsupporting

confidence: 90%

Changes in gut hormones, glycaemic response and symptoms after oesophagectomy

Elliott

Docherty

Murphy

et al. 2019

British Journal of Surgery

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Background: Oesophagectomy is associated with reduced appetite, weight loss and postprandial hypoglycaemia, the pathophysiological basis of which remains largely unexplored. This study aimed to investigate changes in enteroendocrine function after oesophagectomy.Methods: In this prospective study, 12 consecutive patients undergoing oesophagectomy were studied before and 10 days, 6, 12 and 52 weeks after surgery. Serial plasma total fasting ghrelin, and glucagon-like peptide 1 (GLP-1), insulin and glucose release following a standard 400-kcal mixed-meal stimulus were determined. CT body composition and anthropometry were assessed, and symptom scores calculated using European Organisation for Research and Treatment of Cancer (EORTC) questionnaires. Results: At 1 year, two of the 12 patients exhibited postprandial hypoglycaemia, with reductions in bodyweight (mean(s.e.m.) 17⋅1(3⋅2) per cent, P < 0⋅001), fat mass (21.5(2.5) kg versus 25.5(2.4) kg before surgery; P = 0⋅014), lean body mass (51.5(2.2) versus 54.0(1.8) kg respectively; P = 0⋅003) and insulin resistance (HOMA-IR: 0.84(0.17) versus 1.16(0.20); P = 0⋅022). Mean(s.e.m.) fasting ghrelin levels decreased from postoperative day 10, but had recovered by 1 year (preoperative: 621⋅5(71⋅7) pg/ml; 10 days: 415⋅1(59⋅80) pg/ml; 6 weeks: 309⋅0(42⋅0) pg/ml; 12 weeks: 415⋅8(52⋅1) pg/ml; 52 weeks: 547⋅4(83⋅2) pg/ml; P < 0⋅001) and did not predict weight loss (P = 0⋅198). Postprandial insulin increased progressively at 10 days, 6, 12 and 52 weeks (mean(s.e.m.) insulin AUC 0-30 min : fold change 1⋅7(0⋅4), 2⋅0(0⋅4), 3⋅5(0⋅7) and 4⋅0(0⋅8) respectively; P = 0⋅001). Postprandial GLP-1 concentration increased from day 10 after surgery (P < 0⋅001), with a 3⋅3(1⋅8)-fold increase at 1 year (P < 0⋅001). Peak GLP-1 level was inversely associated with the postprandial glucose nadir (P = 0⋅041) and symptomatic neuroglycopenia (Sigstad score, P = 0⋅017, R 2 = 0⋅45). GLP-1 AUC predicted loss of weight (P = 0⋅008, R 2 = 0⋅52) and fat mass (P = 0⋅010, R 2 = 0⋅64) at 1 year.Conclusion: Altered enteroendocrine physiology is associated with early satiety, weight loss and postprandial hypoglycaemia after oesophagectomy.

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Section: Discussionsupporting

confidence: 90%

Changes in gut hormones, glycaemic response and symptoms after oesophagectomy

Elliott

Docherty

Murphy

et al. 2019

British Journal of Surgery

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“…(2007) a 52 156 Total Inverse h NR NR Doecke et al . (2008) a 774 1352 NR NR No association NR Miyazaki et al . (2012) a 25 0 Total NR NR No association Murphy et al .…”

Section: Resultsmentioning

confidence: 99%

“…Studies suggest that physiologic ghrelin responses to fasting and postprandial states are blunted or nonexistent in cancer patients ( Roth et al 2011 , Zub-Pokrowiecka et al 2011 ) and in rats with hepatoma cells (Portau et al 2011). In addition, cancer-related surgeries such as gastrectomy and esophagectomy are associated with decreased serum ghrelin levels, relative to presurgery levels ( Zub-Pokrowiecka et al 2011 , Miyazaki et al 2012 ).…”

Section: Discussionmentioning

confidence: 99%

Is there an effect of ghrelin/ghrelin analogs on cancer? A systematic review

Sever¹,

White²,

García³

2016

Endocrine-Related Cancer

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Ghrelin is a hormone with multiple physiologic functions, including promotion of growth hormone release, stimulation of appetite and regulation of energy homeostasis. Treatment with ghrelin/ghrelin-receptor agonists is a prospective therapy for disease-related cachexia and malnutrition. In vitro studies have shown high expression of ghrelin in cancer tissue, although its role including its impact in cancer risk and progression has not been established. We performed a systematic literature review to identify peer-reviewed human or animal in vivo original research studies of ghrelin, ghrelin-receptor agonists, or ghrelin genetic variants and the risk, presence, or growth of cancer using structured searches in PubMed database as well as secondary searches of article reference lists, additional reviews and meta-analyses. Overall, 45 (73.8%) of the 61 studies reviewed, including all 11 involving exogenous ghrelin/ghrelin-receptor agonist treatment, reported either a null (no statistically significant difference) or inverse association of ghrelin/ghrelin-receptor agonists or ghrelin genetic variants with cancer risk, presence or growth; 10 (16.7%) studies reported positive associations; and 6 (10.0%) reported both negative or null and positive associations. Differences in serum ghrelin levels in cancer cases vs controls (typically lower) were reported for some but not all cancers. The majority of in vivo studies showed a null or inverse association of ghrelin with risk and progression of most cancers, suggesting that ghrelin/ghrelin-receptor agonist treatment may have a favorable safety profile to use for cancer cachexia. Additional large-scale prospective clinical trials as well as basic bioscientific research are warranted to further evaluate the safety and benefits of ghrelin treatment in patients with cancer.

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“…Upper gastrointestinal surgery, such as Roux-en-Y gastric bypass (RYGB), also leads to changes in body weight and appetite, and is often associated with a reduction in ghrelin levels [ 79 , 80 , 81 , 82 ]. Subsequent data, however, show that ghrelin levels frequently return to pre-operative levels within the first year after this surgery in humans [ 83 ] and within six weeks after surgery in mice [ 84 ], with some studies showing an increase in ghrelin post-RYGB [ 85 ].…”

Section: Discussionmentioning

confidence: 99%

The Neurobiological Impact of Ghrelin Suppression after Oesophagectomy

Murphy

Roux

2016

IJMS

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Ghrelin, discovered in 1999, is a 28-amino-acid hormone, best recognized as a stimulator of growth hormone secretion, but with pleiotropic functions in the area of energy homeostasis, such as appetite stimulation and energy expenditure regulation. As the intrinsic ligand of the growth hormone secretagogue receptor (GHS-R), ghrelin appears to have a broad array of effects, but its primary role is still an area of debate. Produced mainly from oxyntic glands in the stomach, but with a multitude of extra-metabolic roles, ghrelin is implicated in complex neurobiological processes. Comprehensive studies within the areas of obesity and metabolic surgery have clarified the mechanism of these operations. As a stimulator of growth hormone (GH), and an apparent inducer of positive energy balance, other areas of interest include its impact on carcinogenesis and tumour proliferation and its role in the cancer cachexia syndrome. This has led several authors to study the hormone in the cancer setting. Ghrelin levels are acutely reduced following an oesophagectomy, a primary treatment modality for oesophageal cancer. We sought to investigate the nature of this postoperative ghrelin suppression, and its neurobiological implications.

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Ghrelin Level and Body Weight Loss After Esophagectomy for Esophageal Cancer

Cited by 23 publications

References 28 publications

Changes in gut hormones, glycaemic response and symptoms after oesophagectomy

Changes in gut hormones, glycaemic response and symptoms after oesophagectomy

Is there an effect of ghrelin/ghrelin analogs on cancer? A systematic review

The Neurobiological Impact of Ghrelin Suppression after Oesophagectomy

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