4.1. Schistosoma infection and colorectal polyps
The distribution of schistosomiasis has obvious regional and sex characteristics. The ratio of intestinal schistosomiasis among men and women was 2.82:1. The number of male infections was significantly higher than that of females, which may be related to the higher number of opportunities for male exposure to contaminated water. Previous surveys have shown that infection rates of schistosomiasis are much higher in adults than in children and adolescents and almost twice as high in adult men as in adult women [7].
Many eggs were deposited in loose connective tissue in the submucosa of the intestinal wall after Schistosoma infection. Due to inflammation and foreign body reaction, tissue necrosis and granulomas formed in the deposition site of the eggs, which then stimulated the proliferation of fibrous tissue and the thickening of the mucosal muscle layer, resulting in yellow nodular changes and vascular network disorder visible to the naked eye under colonoscopy[3]. In our study, all schistosomiasis patients had different degrees of yellow intestinal mucosa, yellow flat or protruding nodules or vascular network disorder, and schistosomal eggs were observed under microscopy. Previous studies have shown that every segment of the intestinal tract of schistosomiasis patients can be involved, but the rectum, sigmoid colon and descending colon supplied by the inferior mesenteric vein were more common, accounting for 90% [8]. Our analysis showed that the rectum and sigmoid colon were the most common intestinal involvement sites of schistosomiasis, and 96.4% of the patients were infected in the descending colon, sigmoid colon or rectum, which was consistent with the above conclusions.
There were 160 cases of intestinal schistosomiasis with intestinal polyps. There was no significant difference in the detection rate of polyps between men and women. However, the incidence of polyps increased with age (p < 0.05). Previous studies have shown that the incidence of polyps in intestinal schistosomiasis patients is in direct proportion to age, and patients over 60 years old with colorectal polyps account for 91.25% of the total samples [9]. Our study revealed that the proportion of polyp patients over 60 years old was 59.4%.
The detection rate of polyps in chronic intestinal schistosomiasis patients was higher than that in the control group (p < 0.05), and rectal polyps were dominant (p = 0.002), which was consistent with the main sites of schistosomiasis infection, indicating that patients with chronic schistosomiasis intestinal infection had a higher risk of colon polyps. Recently, some scholars compared the intestinal polyp characteristics of patients with intestinal schistosomiasis to nonschistosomiasis patients through a retrospective study. The results showed that polyps less than 10 mm and sessile polyps were common in both groups [9]. In our study, the size of polyps in the two groups was also less than 10 mm, accounting for more than 90%. The morphology of polyps was mainly superficial bulges (type IIa) in the two groups (p > 0.05).
Our study showed that the proportion of traditional adenoma in intestinal schistosomiasis patients aged 71 ~ 89 years was higher than that in patients without schistosomiasis (p < 0.001). Therefore, patients exposed to chronic intestinal schistosomiasis may have a higher risk of adenoma. Xiao et al. compared the oncogene expression of schistosomiasis adenomatous polyps, schistosomiasis nonadenomatous polyps and colorectal cancer and found that the expression rate of protooncogenes such as Bcl-2 and CK–20 was higher in adenomatous polyps than in nonadenomatous polyps, and the expression rate of the tumor suppressor gene p27 was significantly lower (p < 0.001). The expression rates of CK-20 and p27 in adenomatous polyps were not significantly different from those in colorectal cancer tissues. Therefore, they believe that adenomatous polyps with schistosomiasis infection are an important factor for canceration [10].
4.2. Schistosoma infection and carcinoma
We found that the combination rate of CRC in women with schistosomiasis was significantly higher than that in the control group (p = 0.017), but there was no difference in the overall detection rate of CRC between the two groups, indicating that chronic schistosomiasis may increase the incidence of colorectal cancer in women. However, the sample size of this study is relatively small, and larger studies are needed to determine whether the conclusion is correct.
Many studies have shown that schistosomiasis is closely related to colorectal cancer. S. japonicum infection is considered an important risk factor for CRC and can increase mortality in CRC patients [8, 11]. The canceration mechanism of schistosomiasis is not fully understood, and inflammation may be the key factor in cancer [12].
Liu et al. retrospectively analyzed 179 cases of intestinal schistosomiasis japonicum disease, among which 32 cases were complicated with colorectal cancer, and concluded that intestinal schistosomiasis was related to the incidence of CRC [13]. Wang et al. compared 30 patients with schistosomiasis rectal cancer (SRC) who underwent laparoscopic total mesorectal resection to 60 CRC patients without schistosomiasis. Multivariate analysis showed that schistosomiasis affected the disease-free survival and overall survival of rectal cancer patients, and the prognosis of SRC was considered to be worse than that of nonschistosomiasis rectal cancer (NSRC) [14]. However, Weng et al. compared 1,800 hot spot mutations in 22 genes of 26 schistosomiasis patients with CRC and 42 patients with simple colorectal cancer by targeted second-generation sequencing technology and found no significant difference between the two groups. They believed that schistosomiasis infection was less correlated with colorectal cancer, but the sample size was small [15].
CRC with chronic schistosomiasis is mostly adenocarcinoma. Canepa et al. reported the first case of rectal signet-ring cell carcinoma [16]. Studies have reported that the average age of CRC patients with schistosomiasis is 6 years younger than that of people without schistosomiasis [17]. However, some studies have shown the opposite [18]. A study of 80 schistosomiasis CRC patients and 258 nonschistosomiasis CRC patients showed that CRC patients with schistosomiasis infection were older (62.2 ± 9.6 y vs 57.2 ± 11.7 y, p = 0.000) [19]. In our study, the average age of CRC patients with schistosomiasis was 69.2 ± 13.4 years, which was higher than that of people without schistosomiasis (p = 0.016).
4.3. Schistosoma infection and colitis
Ulcerative colitis usually presents as extensive and consecutive erosion and multiple shallow ulcerations of the colon, covered with secretions, accompanied by hyperemia, edema or bleeding of surrounding tissue under the endoscope. We compared the erosion and ulceration of the intestinal mucosa between schistosomiasis patients and nonschistosomiasis patients. The ratio of ulceration or erosion in the transverse colon, descending colon and rectum of intestinal schistosomiasis patients was lower than that in the control group, with a large difference, but without statistical significance (p༞0.05). There was no significant difference in the detection rate of ulcerative colitis between the two groups (p > 0.05). We indicated that chronic schistosomiasis infection of the intestine has little influence on the incidence of ulcerative colitis, but it may reduce the risk of scattered ulceration or erosion of the colonic mucosa. A larger sample size is needed for further study.
Previous studies have shown that the incidence of inflammatory bowel disease (IBD) in epidemic areas of parasitic diseases is lower than in other regions [20]. An animal study demonstrated that the deposition of S. japonicum eggs prevented 5% 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice, which may be related to Th1/2 balance and regulation of Toll-like receptor 4[21]. Liu et al. found in a mouse model that S. japonicum infection could prevent dextran sulfate sodium-induced colitis. The reduction in the inflammatory response is related to the Th1/Th2/Th17 pathway, NF-κB pathway and endoplasmic reticulum stress [22]. Wu et al. found that the soluble antigen of adult S. japonicum and recombinant cysteine protease inhibitor protein can alleviate colitis by promoting the immune response mediated by Treg and Th2 and suppressing the Th1 response in mice induced by TNBS [23]. Many animal studies tend to believe that schistosomiasis plays a protective role in IBD. Our study compared general performance, such as ulcers and erosion of the intestinal mucosa, under colonoscopy but lacked research at the pathological and molecular levels.
4.4. Schistosoma infection and hemorrhoids
Clinically, internal hemorrhoids usually appear as the mass of varicose veins above the anorectal odontoid line, where the superior rectal vein and the middle rectal vein respectively drain the blood to the portal vein and the systemic vein [24]. As we know above, schistosomiasis mainly lives in the portal vein and its branches, especially the submesenteric vein, and thus can further reach the superior rectal vein. Therefore, we speculated that the formation of internal hemorrhoids may be related to the chronic inflammation caused by the stimulation of eggs, which aggravates the local venous reflux and affects the structure of the anal cushion. In addition, intestinal symptoms such as diarrhea and bloody stool caused by schistosomiasis may also promote the development of internal hemorrhoids. More research is needed.