Guldenschuh I, Hurlimann R, Muller A, Ammann R, Mullhaupt B, Dobbie Z, Zala G F, Flury R, Seelentag W, Roth J, Meyenberger C, Fried M, Hoppeler T, Spigelman A D, Scott R J
Gastroenterology, Department of Internal Medicine, University Hospital Zurich, Zurich, Switzerland.
Dis Colon Rectum. 2001 Aug;44(8):1090-7; discussion 1097-9. doi: 10.1007/BF02234627.
Familial adenomatous polyposis is an inherited colorectal cancer syndrome characterized by the presence of multiple adenomatous colorectal polyps. Molecular studies have revealed that germline mutations in the APC gene are the underlying cause of the disease. The nonsteroidal anti-inflammatory agent sulindac has been shown to reduce the number of colorectal adenomas. Most sulindac trials in the large bowel have focused on the distal colon and relatively little is known about its effect on the proximal colon. Moreover, it is unknown whether the site of the APC mutation affects the efficacy of sulindac.
This study investigated whether there were regional differences in the effect of sulindac on the colon and whether response to sulindac was dependent on the site of mutation in the APC gene. In an open prospective study 17 patients with familial adenomatous polyposis were treated with 300 mg oral sulindac daily for four months followed by a washout phase of six months. Ten of the patients had an intact colon and seven had rectal stumps only. The number, size, and the degree of dysplasia of the adenomas were evaluated by colonoscopy at entry, end of treatment and end of the study.
Overall, a statistically significant decrease in the number of adenomas was observed (120 +/- 112 to 28 +/- 64, P = 0.007). After cessation of sulindac treatment the number of adenomas increased to 48 +/- 44.5, but remained significantly lower than the values observed at baseline. In the ten patients with intact colons, adenomas decreased by sevenfold in the proximal colon (103 +/- 73 to 15.1 +/- 47.4, P = 0.011) and twofold in the distal colon (80 +/- 52 to 29.6 +/- 37.2, P = 0.005). The size of adenomas and the grade of dysplasia also decreased. No correlation could be seen between the APC mutation site and the response to treatment.
These data indicate that sulindac reduces the number of adenomas in the entire colon and that the effect seems to be more pronounced in the proximal colon.
家族性腺瘤性息肉病是一种遗传性结直肠癌综合征，其特征为存在多个结直肠腺瘤性息肉。分子研究表明，APC基因的种系突变是该疾病的根本原因。非甾体抗炎药舒林酸已被证明可减少结直肠腺瘤的数量。大多数在大肠进行的舒林酸试验都集中在远端结肠，而对其对近端结肠的影响了解相对较少。此外，尚不清楚APC突变位点是否会影响舒林酸的疗效。
本研究调查了舒林酸对结肠的影响是否存在区域差异，以及对舒林酸的反应是否取决于APC基因的突变位点。在一项开放性前瞻性研究中，17例家族性腺瘤性息肉病患者每天口服300毫克舒林酸，持续四个月，随后有六个月的洗脱期。其中10例患者结肠完整，7例仅保留直肠残端。在入组时、治疗结束时和研究结束时通过结肠镜检查评估腺瘤的数量、大小和发育异常程度。
总体而言，观察到腺瘤数量有统计学意义的减少（从120±112个降至28±64个，P = 0.007）。停止舒林酸治疗后，腺瘤数量增加至48±44.5个，但仍显著低于基线时观察到的值。在10例结肠完整的患者中，近端结肠的腺瘤数量减少了7倍（从103±73个降至15.1±47.4个，P = 0.011），远端结肠减少了2倍（从80±52个降至29.6±37.2个，P = 0.005）。腺瘤的大小和发育异常程度也有所降低。未发现APC突变位点与治疗反应之间存在相关性。
这些数据表明，舒林酸可减少整个结肠的腺瘤数量，且这种作用在近端结肠似乎更为明显。
