Calcium and colorectal epithelial cell proliferation: a preliminary randomized, double-blinded, placebo-controlled clinical trial.
Calcium and colorectal epithelial cell proliferation: a preliminary randomized, double-blinded, placebo-controlled clinical trial.
复制标题
钙和结直肠上皮细胞增殖：初步随机、双盲、安慰剂对照临床试验。
DOI：
10.1093/jnci/85.2.132
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Grandits,G
中科院分区：
文献类型：
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作者：
Bostick,RM;Potter,JD;Fosdick,L;Grambsch,P;Lampe,JW;Wood,JR;Louis,TA;Ganz,R;Grandits,G
背景结肠癌高危患者结肠上皮细胞增殖增加.钙的应用改善了啮齿类动物的增殖性变化，在小型的非对照临床试验中的发现表明在人类中也有类似的效果。目的本初步的、双盲的、随机的临床试验设计1）调查补充钙是否会减少消耗高脂肪、西式饮食的散发性腺瘤患者的结肠上皮细胞增殖; 2）以确定样本量（scorable隐窝人数每人）需要达到足够的统计权力;和3），以评估全面的临床trials.MethodsTwenty-one散发性腺瘤患者的可行性进行治疗，每天安慰剂或1200毫克的补充钙。为了确定结肠上皮细胞增殖，我们使用氚化胸苷标记直肠活检标本中的结肠隐窝上皮细胞，并计算标记细胞的百分比（标记指数[LI]）。两名病理学技术人员“阅片人”对每份标本独立评分，并确定阅片人之间的可靠性。受试者在研究期间保持他们的日常饮食，卡路里，钙，总脂肪和维生素D的摄入量在他们之间没有实质性差异。我们计算曲线的统计能力，以确定每个人的可评分隐窝的数量需要检测的统计学显着差异（P<0.05）的平均LI.ResultsThe汇总基线LI为4.7%。在钙治疗组中，LI增加0.6%（成比例增加，12.8%）;在安慰剂治疗组中，LI降低0.5%（成比例降低，10.6%）。安慰剂组与钙剂组从基线至8周随访的平均LI变化之间的差异无统计学显著性。基线LI的阅片者间可靠性的组内相关系数为0.66。分析表明，评分8个隐窝足以估计足够的LI组间比较，在81%的活检samples.ConclusionsCalcium碳酸盐补充剂提供1200毫克元素钙，每天可能不会减少结肠上皮细胞增殖超过8周的时间在散发性腺瘤患者。在未来测量LI的试验中，应考虑确保足够数量的可评分隐窝，以及活检程序不充分、标签失效、读片员可靠性和受试者退出的影响。我们的研究结果支持了一个全面的临床试验的可行性，以进一步研究膳食钙，结肠上皮细胞增殖和结直肠癌之间的关系。[J Natl Cancer Inst 85：132-141，1993]
BackgroundColonic epithelial cell proliferation is increased in patients at high risk for colon cancer. Calcium administration has ameliorated the proliferative changes in rodents, and findings in small, uncontrolled clinical trials have suggested similar effects in humans.PurposeThis preliminary, double-blind, randomized clinical trial was designed 1) to investigate whether supplemental calcium will reduce colonic epithelial cell proliferation in patients with sporadic adenomas who consume a high-fat, Western-style diet; 2) to determine the sample size (number of scorable crypts per person) needed to achieve adequate statistical power; and 3) to evaluate the feasibility of full-scale clinical trials.MethodsTwenty-one sporadic adenoma patients were treated daily with placebo or 1200 mg of supplemental calcium. To determine colonic epithelial cell proliferation, we used tritiated thymidine labeling of colon crypt epithelial cells in rectal biopsy specimens and calculated the percentage of labeled cells (labeling index [LI]). Two pathology technician “readers” independently scored each specimen, and inter-reader reliability was determined. Subjects remained on their usual diet during the study, and intake of calories, calcium, total fat, and vitamin D did not differ substantially among them. We calculated curves for statistical power to determine the number of scorable crypts needed per person for detection of a statistically significant difference (P<.05) of 1.0% in mean LI.ResultsThe pooled baseline LI was 4.7%. In the calcium-treated group, the LI increased 0.6% (proportional increase, 12.8%); in the placebo-treated group, it decreased 0.5% (proportional decrease, 10.6%). The difference between change in the mean LI from baseline to 8 weeks' follow-up in the placebo group versus the calcium group was not statistically significant. The intraclass correlation coefficient for inter-reader reliability for the baseline LI was .66. Analyses indicated scoring eight crypts sufficient for estimates of the LI adequate for between-group comparisons, a level achieved in 81% of biopsy specimens.ConclusionsCalcium carbonate supplements delivering 1200 mg elemental calcium daily may not decrease colonic epithelial cell proliferation over an 8-week period in sporadic adenoma patients. In future trials measuring the LI, consideration should be given to ensuring adequate numbers of scorable crypts and to the impact of inadequate biopsy procedures, labeling failure, reader reliability, and participant withdrawal. Our findings support the feasibility of a full-scale clinical trial to further study the relationships among dietary calcium, colonic epithelial cell proliferation, and colorectal cancer. [J Natl Cancer Inst 85:132–141, 1993]