APACC
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Primary study

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APACC, a French prospective study on aspirin efficacy in reducing colorectal adenoma recurrence: design and baseline findings.

期刊 European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)
Year 2001
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UNLABELLED: Colorectal cancer is the second most frequent cause of death from cancer in western countries. Many lines of evidence suggest that non-steroidal anti-inflammatory drugs (NSAIDs) may offer chemoprevention against colorectal cancer. A multicentre, double-blind, randomized, controlled trial is underway to determine the efficacy of regular aspirin intake (160 or 300 mg/day) in reducing colorectal adenoma recurrence. We now report the baseline characteristics of subjects enrolled into the trial. RESULTS: A total of 618 polyps were excised from 274 patients at the baseline colonoscopy. Men had on average (+/-SD) 2.5 +/- 1.8 polyps per subject and women had 1.7 +/- 1.2. Ninety-one (33.7%) had three or more adenomas and 183 (67.8%) had more than one adenoma measuring 10 mm or more in diameter. The mean (+/-SD) age of the subjects was 57.7 (+/- 9.4) years. Sixty-seven (24.9%) reported that they had previously had adenoma(s), 95 (35.2%) reported a family history of colorectal cancer and 41 (15.2%) a family history of colorectal adenomas. PERSPECTIVE: All subjects will undergo a one-year clearance colonoscopy by February 2001. Clinical, molecular biological and dietary data will enable us to investigate other factors influencing the recurrence of adenomas in this group of high-risk subjects.

Primary study

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每天可溶性阿斯匹林和预防结肠直肠腺瘤的复发：一年通过APACC审判结果。

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期刊 Gastroenterology
Year 2003
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背景与目的：流行病学和实验研究表明，服用阿司匹林可降低大肠癌发生的危险。然而，现有的数据不足以作为公司建议的基础上。方法：我们随机分配272例大肠腺瘤的历史（至少有一个直径超过5毫米，或3个以上）每天赖氨酸乙酰水杨酸（160或300毫克/天）或安慰剂组为4年。主要终点是腺瘤复发后1年和4年。这些结果是今年1结肠镜检查。结果：在完成今年1结肠镜检查的238例患者中，至少有一个腺瘤观察38例患者在阿司匹林组和安慰剂组的112个（41％）46 126（30％）的相对危险性为0.73（95％信心区间[CI]：0.52-1.04，P = 0.08）。至少有一个直径超过5毫米的腺瘤观察13例（10％），阿司匹林组和安慰剂组26（23％）（P = 0.001）。腺瘤超过10毫米直径的相应数字分别为（1％）和7（6％）（p = 0.05）。逐步回归分析表明，较低的腺瘤复发的独立危险因素是阿司匹林治疗（> 5毫米，腺瘤，P = 0.01），进入结肠镜检查前（P = 0.001），没有腺瘤个人历史，以及初始腺瘤性息肉负担少于10毫米（p = 0.001）。结论：每日的水溶性阿司匹林在结肠镜检查发现在开始治疗后1年的经常性腺瘤的风险减少有关。

Systematic review

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阿司匹林的化学预防大肠腺瘤：随机试验的荟萃分析。

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期刊 Journal of the National Cancer Institute
Year 2009
連結 Pubmed DOI PubMed Central
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背景：多行的证据表明，阿司匹林具有抗肿瘤作用在大肠。随机临床试验已进行了评估阿司匹林的有效性，减少大肠腺瘤的危险。这些试验的荟萃分析将提供更精确的估算阿司匹林效果，无论是整体和在分组。方法：我们从所有随机双盲安慰剂对照试验，评价阿司匹林预防大肠腺瘤合并数据。我们采用随机效应荟萃分析估计腺瘤的发生阿司匹林的效果和先进的病变风险比和95％可信区间（CI）（即管状腺瘤，绒毛状腺瘤，腺瘤>或=1厘米直径，高品位发育不良，或浸润性癌）的腺瘤。所有的统计检验双面。结果：我们确定了四个临床试验，2967随机分配的受试者。每个审判评估阿司匹林二级预防大肠腺瘤。测试范围从81到325毫克/ d剂量阿司匹林。与会者在基线时的平均年龄为58​​岁，60％为男性。中位随访33个月。共有2698参与者接受大肠镜随访，腺瘤发生和先进的病变发生后，随机分析。在这些参与者中，被发现在424（37％）分配安慰剂，并在1542参加507（33％）分配给任何剂量阿司匹林1156参与者腺瘤。先进的病变被发现在12％的参与者在安慰剂组中有9％分配给任何剂量阿司匹林的参与者。在任何腺瘤任何剂量阿司匹林与安慰剂的汇集风险比为0.83（95％CI = 0.72〜0.96％）。这相当于绝对风险降低6.7％（95％CI = 3.2％至10.2％）。对于任何先进的病变，所汇集的风险比为0.72（95％CI = 0.57至0.90）。我们没有发现任何基线因素研究的统计显着的效果修改。结论：阿司匹林是有效预防大肠腺瘤在个人与这些病变的历史。

Primary study

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Cyclooxygenase-2 expression and recurrence of colorectal adenomas: Effect of aspirin chemoprevention

期刊 Gut
Year 2010
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Background: Low-dose aspirin reduces the incidence of colorectal cancer and recurrence of adenomas. Cyclooxygenase-2 (COX-2), one of its main target enzymes, is reportedly over-expressed in colorectal adenomas. Aim: To assess COX-2 expression, in relation to adenoma recurrence and the protective effect of aspirin, in a large series of colorectal adenomas, recruited from a double-blind randomised controlled trial comparing recurrences after low-dose aspirin or placebo. Methods: Follow-up colonoscopies were performed after 1 and 4 years to assess adenoma recurrence. COX-2 expression was assessed by immunohistochemistry for each adenoma obtained at baseline colonoscopy, separately for epithelium, deep stroma and overall. Architecture, grade of dysplasia, K-ras mutation, p53 and cyclin D1 expression were studied. Results: COX-2 expression could be assessed in 219 adenomas from 136 patients: 128 adenomas (58%) from 59 patients strongly expressed COX-2. Strong COX-2 expression predominated in adenomas larger than 10 mm (84/129 vs 44/90; p=0.02) and in adenomas showing high-grade dysplasia (22/29 vs 104/188; p=0.04). Deep stromal but not epithelial initial expression of COX-2 predicted adenoma recurrence in the whole population (30/72 patients or 42% strongly expressed deep stromal COX-2 compared with16/64 or 25% without recurrent adenoma; p=0.04). The protective effect of aspirin was mainly observed in patients in whom COX-2 initial expression was low (RR for recurrence in patients taking aspirin with low COX-2 expression: 0.59; 95% CI 0.39 to 0.90; p=0.02). There was no significant effect of aspirin at the end of the trial. Conclusion: Over-expression of COX-2 was frequent and predominated in large and high-grade dysplasia adenomas. Deep stromal but not epithelial initial expression of COX-2 predicted recurrence of adenomas. Aspirin did not act preferentially on patients whose initial adenomas strongly expressed COX-2.

Primary study

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Prevention by daily soluble aspirin of colorectal adenoma recurrence: 4-year results of the APACC randomised trial.

期刊 Gut
Year 2012
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BACKGROUND: Aspirin inhibits colorectal carcinogenesis. In a randomised double-blind placebo-controlled trial, daily soluble aspirin significantly reduced recurrence of colorectal adenomas at 1-year follow-up. In this study the results of daily intake of low-dose aspirin on polyp recurrence at 4-year follow-up are presented. METHODS: 272 patients (naive for chronic aspirin use) with colorectal adenomas were randomly assigned to treatment with lysine acetylsalicylate 160 mg/day (n=73) or 300 mg/day (n=67) or placebo (n=132) for 4 years. The primary endpoints were adenoma recurrence and adenomatous polyp burden at year 4, comparing aspirin at either dose with placebo. The same endpoints were also assessed at year 1 or 4 (last colonoscopy performed for each patient). RESULTS: At the final year 4 colonoscopy the analysis included 185 patients (55 receiving aspirin 160 mg/day, 47 aspirin 300 mg/day and 83 placebo). There was no difference in the proportion of patients with at least one recurrent adenoma between patients receiving aspirin at either dose and those treated with placebo (42/102 (41%) vs 33/83 (40%); NS) or in the adenomatous polyp burden (3.1 ± 5.8 mm vs 3.4 ± 6.2 mm; NS). Also, the proportion of patients with at least one advanced recurrent adenoma did not differ (10/102 [corrected] (10%) in the aspirin group vs 7/83 (8.4%) [corrected] in the placebo group; NS). CONCLUSION: Daily low-dose aspirin decreased adenoma recurrence significantly at 1 year but not at year 4. This discrepancy might be explained by a differential effect of aspirin according to the natural history of the polyp. TRIAL REGISTRATION NUMBER: NCT 00224679.