Melanosis coli: A naturally enhanced contrast for colonoscopy?

Melanosis coli, a dark brown discoloration of the colonic mucosa, is associated with chronic use of anthraquinone laxatives (senna). In addition, Aloe Vera and Rhubarb, used in traditional alternative medicine in Taiwan, are also implicated as the causes of melanosis coli. The term “melanosis,” however, may be misleading, since the pigment responsible for the discoloration is not the deposition of melanin but of lipofuscin in macrophages in the colonic lamina propria. Anthroquinone laxatives induce apoptosis of colon epithelium cells, which are ingested by adjacent macrophages within the mucosa. Those macrophages migrate to the lamina propria and convert the apoptotic cells into lipofuscin with lysozyme. Interestingly, adenomas have impaired absorption of apoptotic debris into the macrophages and thus stand out in the dark mucosa of the melanosis coli as a “pigmentation sparring sign.” Whether melanosis coli increases the risk of colon adenoma and adenocarcinoma is controversial. An early prospective case-control study by Siegers et al suggested anthraquinone laxative abuse was associated with a relative risk of 3.04 (95% confidence interval [CI]: 1.18–4.90) for colorectal cancer. Most recent case-control studies, however, showed that melanosis coli was associated with increased detection of adenomas but not adenocarcinomas. Kassim et al found that patients with melanosis coli were more likely to have both hyperplastic polyp and low-grade adenoma, but not adenocarcinoma. Liu et al found that melanosis coli was associated with higher detection rates of low-grade adenoma (odds ratio [OR] = 1.54; 95% CI: 1.06–2.23; P < .05) but similar detection of high-grade adenomas or adenocarcinomas. Blackett et al showed patients with melanosis were more likely to have an adenoma ≤5 mm (OR = 1.62; 95% CI: 1.04–2.51; P = .03) but not adenomas 6 to 9 mm or ≥10 mm. Abu Baker et al even reported that melanosis coli was associated with less diagnosis of adenocarcinoma than controls (0.3% vs 3.9%; P < .001). Katsumata et al conducted a case-control study in Japan and performed a metaanalysis of five studies at the same time. They concluded that although hyperplastic polyps and adenomas were more frequently detected in patients with melanosis coli, the risk of colorectal cancer was not increased. There are two plausible explanations for the association between melanosis coli and increased detection of adenomas: either melanosis coli promotes the development of adenoma or it facilitates the detection of adenoma. The lack of association between melanosis coli and adenocarcinoma lends support to the latter assumption, as, in accordance with the theory of the colorectal adenoma-carcinoma sequence, increased development of adenoma is supposed to increase the risk of adenocarcinoma. Going a step further than enhancing detection of adenomas, Chan et al proposed that the pigmentation sparring sign may help differentiate adenomas from hyperplastic polyps in this issue of Adv Dig Med. The authors conducted a retrospective review of 571 consecutive colonoscopies for cancer screening in 2014. These store endoscopic images (3–5 frames for each polyp) from patients with melanosis coli and polyps were reviewed by three experienced endoscopists with no prior access to the images. The pigmentation sparring sign was considered positive if two or more endoscopists were in agreement. Twenty-three patients (4%) had melanosis coli. Sixteen of these patients had 35 polyps (21 adenomas and 14 hyperplastic polyps). The average diameter of the adenomas was 3.9 mm (range, 2– 15 mm). The use of the pigmentation sparing sign for predicting adenoma had a sensitivity of 95.2%, a specificity of 78.6%, a positive predictive value of 87.0%, and a negative predictive value (NPV) of 91.7%. The overall accuracy for predicting melanosis coli with the pigmentation sparing sign was 88.6%. Although the reported accuracy of the pigmentation sparring sign is considerably lower than the modern state-of-the-art image enhancing stools, such as narrow band imaging without magnification (sensitivity and accuracy of 96% and 93%, respectively), the numbers are higher than the sensitivity and accuracy of highdefinition white light without using any image enhancing technique (38% and 61%, respectively). The results Received: 29 October 2022 Accepted: 14 November 2022