Abstract
OBJECTIVE To investigate the clinical characteristics of melanosis of the colon (MC) and its correlation with polypus and carcinoma of the large intestine.
METHODS Clinical feature and colonoscopic findings of 156 MC patients were retrospectively analyzed. Final diagnosis of MC case was made after colonoscopic and pathological examination, and data of the case history was recorded.
RESULTS The overall detection rate of MC was 1.12%, with 0.46% in males, 0.66% in females. An 82.69% of the patients suffered various constipations and had a history of taking cathartics. The clinical manifestation of total-colon melanosis occurred in 83.97% of the patients. There was no significant difference between the rate of concomitant polypus (27.56%) in the MC patients and the detection rate of polypus in the patients who underwent a synchronous colonoscopy (χ2 = 1.205, P = 0.298). Also there was no significant difference between the detection rate of carcinoma of the large intestine (8.97%) in MC patients and the detection rate of the same disease in the patients who underwent synchronous colonoscopy (χ2 = 0.268, P = 0.604). A logistic regression analysis has shown that the older the age of MC patients is, the more opportunities of MC and the concomitant polypus would occur.
CONCLUSION MC may be related to constipations and a long-term administration of cathartics, among which total-colon melanosis ranks first in the cases. There is an earlier age of onset in the females, with a higher detection rate. The older the age of the patients is, the higher the detection rate of MC is, and the more possibility the onset of the concomitant polypus.
keywords
Introduction
Melanosis of colon (MC) is a metabolic affection with the characteristic of pigmentation of the colic mucosa[1]. With development and popularity of electronic colonoscopy, the detection rate of MC has been increased, as a result, more and more clinical interests have been driven to it. Over the past few years, related researches and reports on MC were increased in China, however, the etiological factor and pathogenesis of the disease remain unclear, and the relationship between MC and the polypus or carcinoma of large intestine is also a focus of the interests among the researchers at present. In our article, the authors summarized the data of 156 cases with MC diagnosed during 7 years, from 2001-2007, and retrospectively analyzed the characteristics of the case history and endoscopic findings in these patients.
Material and Methods
Clinical data
In our hospital, there were 13,896 patients who underwent a colonoscopy during 7 years, from 2001-2007, of which 7321 were males and 6575 females. In these patients, 156 (1.12%) were diagnosed as MCs, with an average age of 58.57 ± 14.51 ranging from 24-89 years. In the 156 patients, 64 were male, with an average age of 65.53 ± 13.08 ranging from 30-89, and 92 female, with the mean age of 53.73 ± 13.50, ranging from 24-78 (male-female ratio: t = 5.439, P < 0.001).
Observation index
Endoscopic diagnosis of MC
A brown or pitchy pigmented change, and a granular, reticulated or leopard skin and snake-skin like changes, and the main segments of bowels where the lesions located were observed through the endoscopic. The color of MC was pale pitchy in the patients with slight symptom, which was similar to a leopard skin, with apparent asymmetrical milky spots. The vascular lake of the mucosa was ambiguously seen, and most of the lesions occurred on the intestinal mucosa of the colon. The dividing line between the affected mucous membrane of the colon and non-pigmented intestinal mucosa was ill-defined. The color of MC was dark brown (or sable) in the patients with severe symptom. There was some petty linear milky or spot-like mucosa between the sable mucous membranes, and the blood vessel of mucosa was rarely seen, or even the vascular lake vanished. These findings were frequently seen in the type of the total-colon MC (Fig. 1).
Intestinal-mucosa pigmentation shown on an image display of colonoscopy
Pathologic diagnosis of MC
In the interstitial substance of intestinal mucous membrane proper, there was a macrophage sedimentation, with some brown pigment phagocytized by the macrophages at various degree. The epithelial cell layer was normal (Fig. 2).
The macrophage phagocytizing brown pigment granule was seen in the proper layer of intestinal mucosa (H&E stain, × 400)
Data of case history
The major clinical symptom of each patient was recorded, especially the status of defecation, such as constipation or diarrhea, complicated constipation, and whether or not the cathartic drugs were taken, etc.
Concomitant polypus and cancer
The number and sites of the concomitant polypus and cancer in the MC patients and those of polypus in the non-MC patients, and the detection rate of cancer were added up when collecting the data. The statistical analysis of pathological types of the polypus and cancer were also conducted.
Statistical analysis
SPSS 10.0 was used for t test, and the correlation analysis, chi-square test and 2-D logistic regression analysis were also used in the statistical analyses. The value of P < 0.05 was considered as statistically significant.
Results
Habit and character of defecation in the MC patients
Constipation occurred in 82.69% of the cases (129), an alternate constipation and diarrhea in 7.05% (11), and diarrhea in 7.05% (11). No special change of defecation was found in 3.21% of the cases (5).
For the gender constituent ratio of the MC patients who received a synchronous colonoscopy, and the detection rates of the polypus and tumor are shown in Table 1. In the 43 cases with polypus, tubular adenoma was found in 21 (48.84%), hyperplastic polyp in 13 (30.23%) and inflammatory polyp in 9 (20.93%). In 14 cases with carcinoma of large intestine, 10 were rectal cancer (71.43%) and 4 were sigmoid colon carcinoma (28.57%). All of the 14 cases were adeno-carcinomas. In the 43 cases with concomitant polyp, carcinoma of large intestine was found in 3. There was no correlation in incidence between the polyp and cancer (r = -0.043, P = 0.591).
The detection rate of MC and MC with concomitant polyp and cancer in the patients with synchronous colonoscopy (n, %)
For correlation among gender, age and the site of melanosis on intestinal mucosa, see Table 2.
The correlation among gender, age and the site of melanosis on intestinal mucosa
For correlation between the site of pigmentation and colorectal polypus in the MC patients, see Table 3.
Correlation between the site of pigmentation and colorectal polypus in the MC patients
A 2-D logistic regression analysis of the correlation among the polyp, cancer, gender, age and site of malenosis on intestinal mucosa only drew a conclusion that there is a correlation between the onset of the polyp and the age of the MC patients, that is, the older the patient is, the more possibility of MC with concomitant polyp would occur (P = 0.002, relative risk = 1.045).
Discussion
In 1825, Billiand took the initiative in describing the phenomenon of melanin pigmentation on the mucous membrane of colon. Until 1857, Virchow first gave the name of the MC to the disease and kept using it up to now. In addition to colon, the same phenomenon of melanin pigmentation could also occur in esophagus, stomach, duodenum, and ileum etc. In 1928, the causes of MC reported by Bartle, might relate to the administration of the cathartic of anthraquinones, and quite a few MC patients who had the history of taking the cathartic containing anthraquinones could also be seen in clinical reports from China and overseas[2,3]. The incidence rate of MC at overseas was significantly higher than that reported in China. The detection rate of MC was about 10% in the Western countries, or even higher[4], while the detection rate was between 0.06%-5.9% in China, based on data from China[5,6]. After statistically analyzing the findings and results over the past 7 years, it was found that a 82.69% of the MC patients had a history of constipation and taking administration of miscellaneous cathartics which contain anthraquinones, at different dosages. However, the occurrence of diarrhea or alternate constipation and diarrhea was also seen in part of the patients, and even no special changes of the defecation in very few patients that only experienced abdominal pain and distention, hypostatic anal distention (gas pains) etc., or their MC was only discovered by physical examination. Therefore, constipation and administration the cathartics containing anthraquinones fail to completely explain the cause of disease and pathogenesis of MC, so further studies are needed. In our group, the detection rate of MC was 1.12%, with a rate of 0.46% in the males, which was significantly lower than the rate in the females (0.66%) (χ2 = 8.603, P = 0.003). The average age of these MC patients was slightly older (58.5705 ± 14.5083). Among the MC patients, the average age of the onset in the females was significantly lower than that in the males (t = 5.439, P < 0.001), which might relate to a major number of the females with constipation, a slightly earlier age of onset, and an abusage of cathartics containing the anthraquinones.
Based on the results analyzed in the study, 83.97% (131/156) of the MC patients with the clinical manifestation were total-colon mucosal melanosis. There was no significant difference in the site of MC between the males and females (χ2 = 1.002, P = 0.317). Among the MC patients, the older the age of the patients was, the more possibility of total-colon melanosis would occur (t = 2.434, P = 0.016). At present, the relationship among the MC, colon tumor, adenoma of colon and polyp still remains controversial. The results of several clinical researches, including prospective and retrospective studies, on the correlations among the colon melanosis and polyp, especially, the adenomatous polyp and carcinoma of colon, are not quite the same[7-10]. In accordance with the relationship between the sites of polyp and the colon melanosis, the favorite sites of polyp are in order of the descending colon, rectum, transverse colon, sigmoid colon and ascending colon, and most of the polyps occur in the site of melanosis on intestinal mucosa. In 156 MC patients, 27.56% of them suffered concomitant polyp. Comparing the rate of concomitant polypus in the 156 MC patients and the detection rate of polyp (23.84%) in the subjects undergoing a synchronous colonoscopy in our hospital (χ2 = 1.205, P = 0.298), no significant difference was found. There were 14 of the 156 cases (8.97%), whose carcinoma of large intestine was found by the detection of synchronous endoscopy, which had no significant difference compared with the detection rate of the large intestine by synchronous carcinoma in the screening (11.38%) (χ2 = 0.268, P = 0.604). There was no correlation between the concomitant polyp of MC and the concomitant carcinoma. It was thus evident that after a 2-D logistic regression analysis, the incidence of polyp related to the age of the patients, and it didn’t relate to the gender of the patients and the site of melanosis. The older the age of patients was, the more probability of a complicated polyp would occur, which is in conformity with the relationship among incidence, patient’s age and most common site of the polyp that did not occur in colon melanosis[11]. It can be seen that there was no direct correlation between the morbidities of the melanosis and the polyp on the colon. Therefore, the viewpoint of a favorable growth of the polyp, or even the tumor in the MC patients is not supported here. Judging whether or not the melanosis of intestinal mucosa is related to the onset of a polyp that can even develop into a colon and rectal tumor will need more in-depth investigations.
Clinically, MC is a reversible lesion, reversal may occur in many MC patients when they stop taking the cathartic containing anthraquinones, and their manifestation shows a decreased hyper-pigmentation, or even the normal condition of the mucosa was observed under the endoscopy. MC patients do not need any special treatment against the disease. Chronic-constipation patients should increase the intake of dietary fibers, and better stop taking the cathartics containing anthraquinones. Preventing the abusage of the cathartics is the fundamental method of treatment and prevention for the MC patients.
Based on the preliminary study of the 156 patients with MC detected during the past 7 years, we summarize the data in our study mentioned above as follows. The detection rate of MC is 1.12%, and that of the females with MC is higher than that of the males with MC, with an early age of the onset in the females. There is always a correlation among the onset of MC, concomitant polyp and the age of the patients, that is, the older the age of the patients is, the higher the detection rate of MC, and more probability of the concomitant polyp would occur. In order to clarify the relationship among the onset of MC, constipation and a long-term administration of cathartics, as well as their correlation with the polyps in the adenoma of colon and tumors, the first need for the further studies is pathogenesis of MC.
- Received January 8, 2009.
- Accepted March 24, 2009.
- Copyright © 2009 by Tianjin Medical University Cancer Institute & Hospital and Springer
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