Melanosis coli

　　1. Etiology

　　Melanosis coli has no racial heredity, commonly occurs in the elderly, and the exact etiology is still unclear to this day. As early as 1928, Banle proposed the relationship between MC and anthraquinone-type laxatives (73%), and long-term oral intake of laxatives is generally recognized by scholars as the main cause of MC, among which anthraquinone derivatives (such as cascarilla bark, senna leaves, rhubarb soda, etc.) are the main ones. Laxatives made from extracts such as牛黄解毒片 (Niu Huang Jie Du Pian), 麻仁润肠丸 (Ma Ren Ruan Chang Wan), aloe vera, and 果导 (Guo Dao), as well as biphениl methane derivatives (such as bisacodyl), can also cause MC. Moreover, the time and method of taking the medicine also affect the occurrence of MC. There are reports that the shortest time for the occurrence of melanosis coli in patients taking laxatives is 4 months abroad and 1 month in China, with 23.0% occurring within less than 4 months. Another set of materials shows that the incidence of melanosis coli in patients with intermittent medication for less than 1 year is 9.52%; for those with intermittent medication for more than 1 year, it is 11.25%; for those with continuous medication for less than 1 year, the incidence rate of MC is 77.78%; and for those with continuous medication for more than 1 year, the incidence rate is as high as 81.06%. However, not all MC is related to laxatives; about 1/4 of patients who have taken anthraquinone-type laxatives for a long time have no melanosis. And another 1/4 of patients with melanosis have no long-term medication history. Some patients find that as constipation improves, MC also improves or disappears, suggesting that constipation may be one of the causes. In recent years, with the change of people's dietary habits, such as increased intake of fat and protein and reduced intake of fiber, and the increase in patients with defecation difficulties such as constipation, anterior rectal prolapse, and anal-rectal reflex disorder, the number of patients with melanosis coli has increased significantly. Ulcerative colitis may also be another factor leading to MC, with some patients having both ulcerative colitis and melanosis without using laxatives. There are also some patients with chronic diarrhea who develop MC simultaneously, suggesting that chronic diarrhea may also be one of the causes of MC. Some reports indicate that after abdominal gunshots, urinary tract colostomy, the area below the anastomosis also develops melanosis. In addition, some people believe that aging and weakness, decreased gastrointestinal motility, and prolonged retention of feces in the intestines may also be related to MC. Some people also propose that age may affect the occurrence of MC, with the incidence rate significantly higher than other age groups for those over 60 years old (P

　　2, Pathogenesis

　　The various pigments contained in the laxatives are the fundamental cause of the disease. Isek reported a case of a patient who took bamboo leaf extract for 7 years and developed MC, which also proves this point.

　　Various laxatives can cause a transient, dose-related apoptosis of colonic mucosal epithelial cells after entering the large intestine, and the apoptotic bodies produced are engulfed by mononuclear macrophages and migrate to the lamina propria through the basement membrane pores. In the lysosomes of macrophages, the apoptotic bodies are converted into typical lipofuscin or other pigments. With the long-term use of laxatives, these pigmented macrophages continuously accumulate and eventually develop into typical MC changes. Due to the large accumulation of lipofuscin granules in macrophages, severe cases can lead to cell lysis, and the lipofuscin granules gradually spread to the surrounding connective tissue stroma, which can be observed by electron microscopy. This is currently recognized by most scholars as the pathogenesis of MC. Histological studies have shown that the pigment of MC contains glycolipids and glycoproteins, suggesting that it originates from apoptotic epithelial cells or their metabolites, rather than from the laxatives themselves, and the number of apoptotic epithelial cells is positively correlated with the degree of MC. Of course, some people also propose that apoptosis may not be the main mechanism of MC occurrence.

　　There are varying degrees of pigment deposition on the normal mucosa of the colon, which presents as brown, brown, black striped or tiger skin-like localized or diffuse distribution. In patients with polyps, the mucosa appears pink or white, and the submucosal vascular network is unclear. Under the light microscope, the colonic mucosal epithelial cells are roughly normal, the submucosal layer is thickened and edematous, and there are a large number of dense or scattered macrophages in the lamina propria, with irregular morphology, cytoplasm filled with pigment granules, and the nucleus obscured. Sometimes pigment granules can also be seen outside the macrophages. In severe cases of colorectal melanosis, macrophages containing pigment granules can also be seen in the submucosa or mesenteric lymph nodes, and at this time, melanin staining (Fontana silver staining) is positive and iron staining is negative. Under electron microscopy, the lamina propria shows a significant increase in the number and size of macrophages. There is a large amount of lipofuscin deposition in the cytoplasm and surrounding connective tissue. Near the myelinated nerve fibers of the intestinal wall plexus, macrophages containing lipofuscin granules can also be seen, along with the phagocytosis phenomenon of fibroblasts.

　　The relationship between tumors and colorectal melanosis is that patients with colorectal melanosis have a higher incidence of colorectal cancer. Morgenstern statistically analyzed 511 specimens of colorectal cancer resection, of which 5.9% were accompanied by melanosis. Zhao Dongli and others reported that among 38 cases of MC, 2 were accompanied by colorectal cancer, 3 by colorectal adenomatous polyps, 1 with rectal polyps, and 2 with colorectal cancer found after surgery. The reason why patients with colorectal melanosis are prone to cancer and polyps may be related to the damage to the intestinal mucosa caused by laxatives and the pigment deposition of MC. Some studies have already shown that certain active ingredients in natural or synthetic laxatives have potential genotoxicity and carcinogenicity.

　　Melanosis coli has no specific symptoms and signs, mainly including abdominal distension, constipation, and difficulty in defecation. A few patients have lower abdominal pain and poor appetite, which may be related to the invasion of the melanosis into the colonic plexus, causing degenerative changes in the mucosal plexus, leading to intestinal dysfunction and electrolyte disorder. A few patients have hypokalemia, hyponatremia, and hypocalcemia, and occasionally there may be edematous narrowing of the colon. Some reports suggest that this disease often occurs with colorectal cancer, adenoma, and polyps.

　　There are no effective preventive measures at present; early detection and early diagnosis are the key to the prevention and treatment of the disease.

　　1. Establish good defecation habits

　　It is necessary to develop the habit of defecating at a regular time. When defecating, one should concentrate their attention and not read newspapers or do other things.

　　2. Increase fiber intake

　　Fiber-rich foods include bran or brown rice, vegetables such as celery and chives, and increase water intake to enhance the stimulation of the colon.

　　3. Increase the amount of exercise

　　Therefore, it is recommended to take a walk, go for a slow run, or do exercises in the morning. If there is no time, more half-squatting movements can be done in the office, which can also exercise the abdominal muscle tension and compensate for insufficient exercise.

　　Blood routine examination is normal, and a few patients may have hyponatremia, hypokalemia, or hypocalcemia.

　　Colonoscopy examination:

　　The endoscopic manifestation of melanosis coli includes smooth and intact colonic mucosa, with light brown, brownish, or black pigmentation that appears streaky, patchy, or tiger-skin-like, which may be discontinuously or continuously distributed in a network pattern. The intestinal lumen becomes明显 darker, and white or pink polyps may be elevated. In some cases, the mucosa shows no significant coloring, but an unexpected biopsy of a polyp in the sigmoid colon confirms it as MC. According to the degree of mucosal pigmentation, MC is divided into three degrees: Degree I, with light black pigmentation resembling leopard skin, the mucosal vascular patterns are faintly visible, the lesions are mostly localized, and the boundary with normal mucosa is not very clear; Degree II, dark brownish, with linear whitish mucosa between the dark brownish mucosa, more common in the left half of the colon or on a segment of colonic mucosa, the mucosal blood vessels are not clear, and there is a clear boundary with normal mucosa; Degree III, deep blackish brown, with fine whitish linear or dot-like mucosa between the deep blackish brown mucosa, submucosal blood vessels are not visible, and this type of manifestation is more common in the total colon type. From the perspective of the site of the lesion, if the lesion is localized, it is more common in the proximal colon, and in severe cases, it can affect the entire colon. In the statistics of 261 cases of MC in China, the left half of the colon accounts for about 32.84%, the right half of the colon accounts for 11.94%, the transverse colon accounts for 26.87%, and the total colon involvement accounts for 28.36%. It is more obvious at the hepatic flexure, splenic flexure, the junction of the descending sigmoid colon, and above the anastomosis.

    The diet of patients with colorectal melanosis should be light, easy to digest, eat more vegetables and fruits, and reasonably match the diet, pay attention to adequate nutrition. In addition, patients should also pay attention to avoiding spicy, greasy, and cold foods.

　　1. Treatment

　　There is currently no effective drug treatment for MC. Most scholars believe that MC is a benign reversible non-inflammatory intestinal mucosal lesion. With the improvement of constipation symptoms and the discontinuation of laxatives, a large amount of lipofuscin is digested and decomposed by lysosomes, and the pigmentation of MC can be reduced or even disappear. Therefore, it is recommended to eat more vegetables, fruits, and fiber-rich foods, drink more water, exercise more, reduce constipation or difficulty in defecation, develop good defecation habits, stop using or not using colored laxatives and instead use oily laxatives, and use gastrointestinal motility drugs and microecological preparations as necessary to relieve constipation, which can reduce the incidence of MC and reverse the existing lesions. Treatment should be given to some causes that may cause melanosis, such as rectal prolapse repair and intussusception fixation surgery. For patients diagnosed with MC, regular follow-up colonoscopy should be performed to detect accompanying colon polyps, adenomas, and colorectal cancer in time, and early endoscopic high-frequency electrocision or surgical resection treatment should be performed. However, for those without a history of taking laxatives but suffering from the disease, the treatment method needs further exploration.

　　2. Prognosis

　　Most scholars believe that colorectal melanosis is a benign reversible damage that can coexist with colorectal cancer. Regular follow-up colonoscopy is very necessary.