Cats A, Dullaart R P, Kleibeuker J H, Kuipers F, Sluiter W J, Hardonk M J, de Vries E G
Division of Medical Oncology, University Hospital, Groningen, The Netherlands.
Cancer Res. 1996 Feb 1;56(3):523-6.
To gain insight into the possible physiological mechanisms responsible for the increased incidence of colonic neoplasms in patients with acromegaly, a prospective cohort study was carried out in 30 patients with acromegaly, a prospective cohort study was carried out in 30 patients with acromegaly. Seven patients had newly diagnosed acromegaly and 23 were studied during follow-up. Serum growth hormone and insulin-like growth factor-1 (IGF-1) were determined on two separate occasions. During diagnostic endoscopy, mucosal biopsies were obtained for immunohistochemical determination of sigmoidal epithelial cell proliferation, expressed as labeling index (LI). Duodenal and fecal bile acid analyses were performed using gas-liquid chromatography. Results were compared with normal ranges of the laboratory. An increased overall LI was found in 54% of the patients. Increased LI of the luminal, middle, and basal crypt compartments was found in 11, 64, and 28%, respectively. Similarly, comparisons of the mean +/- SEM of the overall LI and the LI of the middle and basal compartments between acromegalic patients and a control group showed overall LI 10.0 +/- 0.8% versus 5.7 +/- 0.6% (P < 0.001), middle LI 12.1 +/- 1.2% versus 5.0 +/- 0.6% (P < 0.001), and basal LI 17.1 +/- 1.3% versus 10.8 +/- 1.3% (P < 0.01). Duodenal and fecal bile acid proportions were within the normal ranges of the laboratory. There was a positive correlation between growth hormone and overall LI (r = 0.55, P < 0.01) by least square regression analysis. There was no correlation between duodenal bile acid composition and hormone levels. The proportion of secondary bile acids in feces correlated with growth hormone (r = 0.55, P < 0.05) as well as with IGF-1 (r = 0.59, P < 0.05). With multiple regression analyses, only a relation between overall LI and IGF-1 (P = 0.007) remained to hold true. Increased epithelial cell proliferation, most probably due to a direct stimulatory effect of especially IGF-1, contributes to the increased risk of colonic neoplasms in acromegaly.
为深入了解肢端肥大症患者结肠肿瘤发病率增加可能的生理机制，对30例肢端肥大症患者进行了一项前瞻性队列研究。7例患者为新诊断的肢端肥大症，23例在随访期间接受研究。在两个不同时间点测定血清生长激素和胰岛素样生长因子-1（IGF-1）。在诊断性内镜检查时，获取黏膜活检组织用于免疫组化测定乙状结肠上皮细胞增殖情况，以标记指数（LI）表示。采用气液色谱法进行十二指肠和粪便胆汁酸分析。结果与实验室正常范围进行比较。54%的患者总体LI升高。管腔、中间和基底隐窝区LI升高的患者分别占11%、64%和28%。同样，肢端肥大症患者与对照组之间总体LI以及中间和基底区LI的均值±标准误比较显示，总体LI分别为10.0±0.8%和5.7±0.6%（P<0.001），中间LI分别为12.1±1.2%和5.0±0.6%（P<0.001），基底LI分别为17.1±1.3%和10.8±1.3%（P<0.01）。十二指肠和粪便胆汁酸比例在实验室正常范围内。通过最小二乘法回归分析，生长激素与总体LI之间存在正相关（r = 0.55，P<0.01）。十二指肠胆汁酸组成与激素水平之间无相关性。粪便中次级胆汁酸比例与生长激素（r = 0.55，P<0.05）以及与IGF-1（r = 0.59，P<0.05）相关。通过多元回归分析，仅总体LI与IGF-1之间的关系（P = 0.007）仍然成立。上皮细胞增殖增加，很可能特别是由于IGF-1的直接刺激作用，导致肢端肥大症患者结肠肿瘤风险增加。
