DOI: https://doi.org/10.21203/rs.3.rs-2831569/v1
Background:
Schistosomiasis, as the second largest parasitic disease in the world, has infected more than 200 million people. Previous studies have found a correlation between schistosomiasis and the occurrence and development of colorectal cancer. However, there is still a lack of large-scale studies reporting whether schistosomiasis affects the prognosis of colorectal cancer and the treatment standards for schistosomiasis-associated colorectal cancer. This study aims to investigate the clinicopathological characteristics and prognosis of colorectal cancer patients with chronic schistosomiasis (CRCS+).
Methods:
We collected data from 94 CRCS+ patients diagnosed at Xiangya Hospital of Central South University between January 1, 2014 and December 31, 2019. Using propensity score matching, we selected 94 colorectal cancer patients without chronic schistosomiasis (CRCS−) and retrospectively analyzed the clinical and pathological data of both groups.
Results:
Compared to CRCS− patients, CRCS+ patients exhibited distinct clinicopathological features such as regional clustering, advanced age, severe liver function impairment, and a lower positive rate of fecal monoclonal blood tests. Calcification was a characteristic feature of CRCS+ patients. Overall survival was worse for colorectal cancer patients with chronic schistosomiasis.
Conclusions:
Schistosomiasis may be considered an independent risk factor for colorectal cancer.
According to the latest data released by the International Agency for Research on Cancer, there were 19.3 million new cases of cancer and 10 million cancer-related deaths worldwide in 2020. Colorectal cancer accounted for over 1.9 million new cases and 935,000 deaths, ranking third in incidence and second in mortality among all malignant tumors [1]. There is no single risk factor for colorectal cancer. In addition to family history [2, 3], smoking [4, 5], alcohol consumption [6, 7], obesity [8, 9], diabetes [10–12], consumption of red or processed meat [13, 14], and inflammatory colorectal lesions are also considered risk factors for colorectal cancer [15, 16]. Currently, TNM staging is commonly used to evaluate the prognosis of patients with colorectal cancer after surgical resection and to guide drug treatment. However, there are many factors that affect the prognosis of colorectal cancer, including the tumor microenvironment, among others, in addition to histopathology. TNM staging lacks multi-dimensional considerations, and postoperative evaluation based solely on TNM staging is not completely accurate. Even in the early stages, there is a risk of recurrence and metastasis of colorectal cancer. Therefore, it is necessary to identify additional indicators that may be related to the prognosis of colorectal cancer to accurately predict prognosis and guide individualized drug treatment.
Schistosomiasis is a zoonotic disease and the second most common parasitic infection worldwide after malaria, with over 200 million people infected, primarily in tropical and subtropical regions [17–19]. Several species of schistosomes can infect humans, but Schistosoma japonicum is the predominant species in China. Oncomelania is the only intermediate host of Schistosoma japonicum, and it is widely distributed and difficult to control. Schistosomiasis was once one of the five major parasitic diseases in China. However, after years of control efforts, schistosomiasis has shown only low prevalence in recent years. According to epidemiological surveys, at the end of 2020, there were 450 schistosomiasis-endemic counties/cities/districts in China, affecting a total population of approximately 71.3704 million people [20]. In 2020, new cases of advanced schistosomiasis in China were mainly concentrated in Hunan, Hubei, and Jiangxi provinces. By 2019, Hunan Province still had an Oncomelania area of 173,000 hm2, accounting for 47.7% of China’s total Oncomelania area and making it the largest endemic area for schistosomiasis and the province with the largest Oncomelania coverage in China. Dongting Lake, located in Hunan Province, is the second largest freshwater lake in China. Its geographical location and rich freshwater resources provide favorable conditions for Oncomelania growth. The surrounding area of Dongting Lake is also a difficult area for schistosomiasis control. Schistosome damage to the human body is mainly caused by eggs deposited in the intestinal wall tissues of the rectum, colon, and appendix, causing congestion, edema, and necrosis of the intestinal mucosa. Severe inflammatory reaction leads to mucosal ulceration, microabscess formation, polyposis, and neoplastic transformation [21]. Schistosome infection has been associated with various human malignancies, including bladder cancer, liver cancer, and colorectal cancer, but the specific mechanisms are still unclear [22].
The first reported case of colorectal cancer complicated with schistosomiasis dates back to 1932, and since then, numerous studies have reported cases of colorectal cancer with schistosomiasis. Schistosome egg deposition can cause local long-term chronic inflammation. Recent studies suggest that chronic inflammation caused by schistosomiasis may be a risk factor for colorectal cancer, but there are few large-scale studies on whether schistosomiasis affects the prognosis of colorectal cancer.
The aim of this study is to investigate whether chronic schistosomiasis is a negative prognostic factor for colorectal cancer by analyzing the clinicopathological data and overall survival time (OS) of colorectal cancer patients both with and without chronic schistosomiasis.
This study gathered clinical and pathological data of patients who underwent colorectal cancer surgery at Xiangya Hospital of Central South University between January 1, 2014, and December 31, 2019. 94 patients with colorectal cancer were pathologically diagnosed with schistosome eggs, while 6025 patients were diagnosed without schistosome eggs based on the inclusion and exclusion criteria. Propensity score matching was performed based on gender, age, tumor location, year of surgery, TNM stage, and preoperative chemotherapy. As a result, a total of 94 colorectal cancer patients without chronic schistosomiasis were randomly matched in a 1:1 ratio.
Inclusion criteria:
Surgery performed between January 1, 2014 and December 31, 2019.
Complete clinical and pathological data were available.
Exclusion criteria:
Patients with concurrent malignant tumors or previous history of malignant tumors.
Postoperative pathological results showed non-adenocarcinoma type tumor.
Data collected included gender, age, residence, history of intestinal obstruction, blood routine examination, liver function, tumor markers (CA125, CA199, CEA and AFP), blood type, fecal monoclonal occult blood test, colonoscopy, CT, tumor TNM staging, chemotherapy, etc. Variables extracted from patients’ medical records appear in Tables 1 to 7.
Follow-up was conducted through outpatient visits and telephone interviews until August 2022. The primary outcome was overall survival (OS), calculated from the date of surgery to the death of patients due to any cause or the end of follow-up.
All data were analyzed using SPSS 27.0 software. Clinical data were analyzed using t-tests and chi-square tests. Kaplan-Meier and Log-Rank methods were used to calculate survival rates and plot survival curves. P-values < 0.05 was considered statistically significant.
This study included 94 colorectal cancer patients with chronic schistosomiasis (CRCS+) who underwent surgery at Xiangya Hospital of Central South University between January 1, 2014 and December 31, 2019. Analysis of patient residence showed that all but two patients (who lived along the Yangtze River in Jingzhou City, Hubei Province) lived in Dongting Lake and its tributaries, including 43 patients in Yueyang City, 24 in Yiyang City, 17 in Changde City, 5 in Changsha City, 2 in Yongzhou City, and 1 in Hengyang City, Hunan Province. All patients had a history of contact with schistosomiasis water. The distribution of patients is shown in Fig. 1.
According to TNM stage, 17 CRCS+ patients (18.1%) were stage I; 41 (43.6%) were stage II; 32 (34.0%) were stage III; and 4 (4.3%) were stage IV. By tumor location, 47 cases (50.0%) were rectal cancer; 16 (17.0%) were sigmoid colon cancer; 7 (7.4%) were left colon cancer; and 24 (25.5%) were right colon cancer.
A total of 6025 colorectal cancer patients without schistosomiasis who met the inclusion and exclusion criteria and underwent surgery at Xiangya Hospital of Central South University between January 1, 2014 and December 31, 2019 were included in this study. Of these patients, 782 (13.0%) were stage I; 2158 (35.8%) were stage II; 2525 (41.9%) were stage III; and 560 (9.3%) were stage IV. By tumor location, 3005 cases (49.9%) were rectal cancer; 1085 (18.0%) were sigmoid colon cancer; 504 (8.4%) were left colon cancer; 71 (1.2%) were transverse colon cancer; and 1360 (22.6%) were right colon cancer.
The proportion of CRCS+ patients at stages I and II (61.7%) was higher than that of patients without schistosomiasis (48.8%), although the difference was not statistically significant (P = 0.062). There was no significant difference in tumor location between CRCS+ patients and patients without schistosomiasis (P = 0.807). See Table 1.
Gender was compared between CRCS+ patients and the 6025 colorectal cancer patients without schistosomiasis. Among CRCS+ patients, there were 64 males (68.1%) and 30 females (31.9%). Among the 6025 patients without schistosomiasis, there were 3606 males (59.9%) and 2419 females (40.1%). The proportion of males was higher among CRCS+ patients, but the difference was not statistically significant (P = 0.106).
The age of CRCS+ patients ranged from 29 to 81 years, with an average age of 66.13 ± 9.23 years; among them, 79 cases (84.0%) were over 60 years old. In contrast, the age of colorectal cancer patients without schistosomiasis ranged from 14 to 92 years, with an average age of 58.35 ± 12.07 years; among them, 2973 cases (49.3%) were over 60 years old. The proportion of patients aged over 60 years was significantly higher in CRCS+ patients compared to patients without schistosomiasis (P < 0.001), as shown in Fig. 2.
| Clinicopathological characteristics | CRCS+ | 6025 Colorectal cancer patients without schistosomiasis | P-value | |
|---|---|---|---|---|
| TNM | I | 17(18.1%) | 782(13.0%) | 0.062 |
| II | 41(43.6%) | 2158(35.8%) | ||
| III | 32(34.0%) | 2525(41.9%) | ||
| IV | 4(4.3%) | 560(9.3%) | ||
| Location | Rectum | 47(50.0%) | 3005(49.9%) | 0.807 |
| Sigmoid colon | 16(17.0%) | 1085(18.0%) | ||
| Left colon | 7(7.4%) | 504(8.4%) | ||
| Right colon | 24(25.5%) | 1360(22.6%) | ||
| Transverse colon | 0(0.0%) | 71(1.2%) | ||
| Gender | male | 64(68.1%) | 3606(59.9%) | 0.106 |
| female | 30(31.9%) | 2419(40.1%) | ||
| Age | ≤ 50 | 5(5.3%) | 1568(26.0%) | P<0.001 |
| 51–60 | 11(11.7%) | 1670(27.7%) | ||
| 61–70 | 50(53.2%) | 1866(31.0%) | ||
| 71–80 | 24(25.5%) | 755(12.5%) | ||
| ≥ 81 | 4(4.3%) | 166(2.8%) | ||
| CRCS+: colorectal cancer patients with chronic schistosomiasis | ||||
To reduce potential confounding factors, propensity score matching was performed based on gender, age, tumor location, year of surgery, TNM stage, and preoperative chemotherapy. As a result, a total of 94 colorectal cancer patients without chronic schistosomiasis (CRCS−) were randomly matched in a 1:1 ratio. See Table 2.
| Variable | CRCS+(N = 94) | CRCS−(N = 94) | P-value | |
|---|---|---|---|---|
| Gender | male | 64(68.1%) | 64(68.1%) | 1.000 |
| female | 30(31.9%) | 30(31.9%) | ||
| Age | 66.1 ± 9.23 | 65.6 ± 8.94 | 0.665 | |
| Year of operation | 2014 | 18(19.1%) | 13(13.8%) | 0.807 |
| 2015 | 16(17.0%) | 19(20.2%) | ||
| 2016 | 9(9.6%) | 13(13.8%) | ||
| 2017 | 16(17.0%) | 18(19.1%) | ||
| 2018 | 21(22.3%) | 20(21.3%) | ||
| 2019 | 14(14.9%) | 11(11.7%) | ||
| Location | Rectum | 47(50.0%) | 48(51.1%) | 0.627 |
| Sigmoid colon | 16(17.0%) | 21(22.3%) | ||
| Left colon | 7(7.4%) | 5(5.3%) | ||
| Right colon | 24(25.5%) | 19(20.2%) | ||
| Transverse colon | 1(1.1%) | 1(1.1%) | ||
| TNM | I | 17(18.1%) | 25(26.6%) | 0.308 |
| II | 41(43.6%) | 40(42.6%) | ||
| III | 32(34.0%) | 28(29.8%) | ||
| IV | 4(4.3%) | 1(1.1%) | ||
| Chemotherapy | yes | 10(10.6%) | 5(5.3%) | 0.178 |
| no | 84(89.4%) | 89(94.7%) | ||
According to the patients' medical history, imaging data, and surgical records, 9 cases (9.6%) of CRCS+ patients had intestinal obstruction before surgery. Among CRCS− patients, 8 cases (8.5%) had intestinal obstruction before surgery, and there was no significant difference between the two groups (P = 0.799).
The preoperative colonoscopy reports revealed that 27 CRCS+ patients (28.7%) had multiple colon polyps (≥ 2). Similarly, 27 CRCS− patients (28.7%) had multiple colon polyps, and there was no significant difference observed between the two groups (P = 1.000).
Preoperative blood routine examination results were compared between CRCS+ and CRCS− patients; for patients with a history of chemotherapy, results before the first chemotherapy were taken into account. The blood routine indicators analyzed in this study included white blood cell count, red blood cell count, hemoglobin, platelet count, neutrophil count, lymphocyte count, eosinophil count, basophil count, monocyte count, neutrophil ratio, lymphocyte ratio, eosinophil ratio, basophil ratio, and monocyte ratio. The study found no significant difference in these blood routine examination results between the two patient groups. See Table 3.
Preoperative liver function results were compared between CRCS+ and CRCS− patients; for patients with a history of chemotherapy, results before the first chemotherapy were taken into account. The level of aspartate aminotransferase was significantly higher in CRCS+ patients than in CRCS− patients; the difference between the two groups was statistically significant (P = 0.047). However, no significant differences were observed in other liver function indicators such as total protein, albumin, globulin, total bilirubin, direct bilirubin, total bile acid, and alanine aminotransferase between the two groups. See Table 4.
In this study, 74 CRCS+ patients (78.7%) tested positive and 20 (21.3%) tested negative for fecal monoclonal occult blood test before surgery. Among CRCS− patients, 84 (89.4%) tested positive and 10 (10.6%) tested negative for fecal monoclonal occult blood before surgery. The difference was statistically significant (P = 0.046).
| Variable | CRCS+ | CRCS- | P-value |
|---|---|---|---|
| White blood cell count(10^9/L) | 6.25 ± 1.97 | 6.29 ± 1.77 | 0.907 |
| Red blood cell count(10^12/L) | 4.17 ± 0.56 | 4.21 ± 0.55 | 0.633 |
| Hemoglobin(g/L) | 120.48 ± 22.27 | 121.86 ± 22.04 | 0.669 |
| Platelet(10^9/L) | 237.73 ± 114.03 | 227.46 ± 81.85 | 0.479 |
| Neutrophil count(10^9/L) | 4.01 ± 1.64 | 3.93 ± 1.45 | 0.735 |
| Lymphocyte count(10^9/L) | 1.53 ± 0.55 | 1.66 ± 0.62 | 0.126 |
| Eosinophil count(10^9/L) | 0.18 ± 0.18 | 0.19 ± 0.13 | 0.852 |
| Basophil count(10^9/L) | 0.02 ± 0.04 | 0.02 ± 0.04 | 0.865 |
| Monocyte count(10^9/L) | 0.50 ± 0.20 | 0.48 ± 0.16 | 0.428 |
| Neutrophil ratio(%) | 62.92 ± 9.50 | 61.72 ± 8.31 | 0.355 |
| Lymphocyte ratio(%) | 25.47 ± 8.85 | 26.90 ± 8.12 | 0.251 |
| Basophil ratio(%) | 0.55 ± 0.34 | 0.61 ± 0.43 | 0.229 |
| Eosinophil ratio(%) | 2.90 ± 2.18 | 3.12 ± 2.23 | 0.501 |
| Monocyte ratio(%) | 8.11 ± 2.22 | 7.66 ± 1.65 | 0.113 |
CRCS+: colorectal cancer patients with chronic schistosomiasis CRCS-༚colorectal cancer patients without chronic schistosomiasis
| Variable | CRCS+ | CRCS- | P-value |
|---|---|---|---|
| Total protein(g/L) | 66.17 ± 6.63 | 67.74 ± 6.14 | 0.093 |
| Albumin(g/L) | 39.04 ± 5.05 | 39.99 ± 4.63 | 0.177 |
| Globulin(g/L) | 27.13 ± 4.36 | 27.75 ± 3.92 | 0.308 |
| Total bilirubin (µmol/L) | 9.97 ± 4.36 | 9.64 ± 4.40 | 0.604 |
| Direct bilirubin(µmol/L) | 4.25 ± 1.94 | 3.98 ± 1.87 | 0.333 |
| Total bile acid(µmol/L) | 5.68 ± 6.78 | 4.73 ± 4.27 | 0.255 |
| Alanine aminotransferase(U/L) | 19.35 ± 13.57 | 16.45 ± 8.49 | 0.081 |
| Aspartate aminotransferase(U/L) | 23.53 ± 9.86 | 21.14 ± 6.06 | 0.047 |
CRCS+: colorectal cancer patients with chronic schistosomiasis CRCS-༚colorectal cancer patients without chronic schistosomiasis
Blood type was compared between the two groups. Among CRCS+ patients, there were 31 cases (33.0%) with blood type A, 26 (27.7%) with blood type B, 24 (25.5%) with blood type O, and 13 (13.8%) with blood type AB. Among CRCS− patients, there were 33 cases (35.1%) with blood type A, 15 (16.0%) with blood type B, 39 (41.5%) with blood type O, and 7 (7.4%) with blood type AB. The difference between the two groups was statistically significant (P = 0.039). See Table 5.
| Variable | CRCS+ | CRCS- | P-value | |
|---|---|---|---|---|
| Blood type | A | 31(33.0%) | 33(35.1%) | 0.039 |
| B | 26(27.7%) | 15(16.0%) | ||
| O | 24(25.5%) | 39(41.5%) | ||
| AB | 13(13.8%) | 7(7.4%) | ||
CRCS+: colorectal cancer patients with chronic schistosomiasis CRCS-༚colorectal cancer patients without chronic schistosomiasis
Preoperative tumor marker results were compared between CRCS+ and CRCS− patients; for patients with a history of chemotherapy, results before the first chemotherapy were taken into account. This study compared CA125, CA199, CEA, and AFP levels but found no significant difference between the two groups. See Table 6.
| Variable | CRCS+ | CRCS- | P-value |
|---|---|---|---|
| CA125 | 8.52 ± 6.47 | 7.22 ± 5.99 | 0.155 |
| CA199 | 22.47 ± 55.78 | 15.94 ± 24.31 | 0.299 |
| CEA | 10.74 ± 20.72 | 14.03 ± 50.10 | 0.558 |
| AFP | 2.32 ± 1.98 | 2.00 ± 1.29 | 0.186 |
CRCS+: colorectal cancer patients with chronic schistosomiasis CRCS-༚colorectal cancer patients without chronic schistosomiasis
This study found that 18 CRCS+ patients (19.1%) had intestinal calcification on preoperative CT images while none of the CRCS− patients had intestinal calcification on preoperative CT images; the difference between the two groups was statistically significant (P < 0.001). See Fig. 3.
By reviewing preoperative CT imaging data, this study found that 6 CRCS+ patients had preoperative cirrhosis while none of the CRCS− patients had preoperative cirrhosis. Further analysis of blood routine examination and CT imaging was performed to compare whether the two groups of patients had portal hypertension before surgery. The main indicators were: 1) splenomegaly, with spleen long axis > 10cm and thickness diameter > 4.5cm; 2) preoperative white blood cell count < 4×109/L or platelet count < 100×109/L; 3) CT showing esophageal or gastric fundus varices; 4) portal vein width > 14mm or splenic vein width > 10mm. Patients meeting two or more criteria were diagnosed with portal hypertension. In this study, 2 CRCS+ patients were diagnosed with portal hypertension while none of the CRCS− patients were diagnosed with portal hypertension. Further comparison of Child-Pugh scores between the two groups showed that among CRCS+ patients, 87 had Child-Pugh grade A, 7 had grade B, and 0 had grade C. Among CRCS− patients, 86 had Child-Pugh grade A, 8 had grade B, and 0 had grade C. There was no significant difference between the two groups (P = 0.788). See Table 7.
| Variable | CRCS+ | CRCS- | P-value | |
|---|---|---|---|---|
| Cirrhosis | 6 | 0 | 0.013 | |
| Portal hypertension | 2 | 0 | 0.155 | |
| Child-Pugh score | Child-Pugh A | 87 | 86 | 0.788 |
| Child-Pugh B | 7 | 8 | ||
| Child-Pugh C | 0 | 0 | ||
CRCS+: colorectal cancer patients with chronic schistosomiasis CRCS-༚colorectal cancer patients without chronic schistosomiasis
Follow-up was conducted through outpatient visits and telephone interviews to record the OS of both groups of patients. By August 2022, 53 out of 188 patients had passed away, with 35 deaths occurring in CRCS+ patients and 18 deaths in CRCS− patients. Survival curves were plotted using the Kaplan-Meier method, as depicted in Fig. 4, and OS values for CRCS+ and CRCS− patients were compared using the Log-rank statistical method. The analysis revealed a statistically significant difference between the two groups (P = 0.005).
The field of colorectal cancer has seen significant advances in both basic and clinical medical research, along with the development and application of new drugs, resulting in improved five-year survival rates. However, despite these advancements, colorectal cancer remains the second leading cause of cancer-related deaths [1]. Therefore, further in-depth study of colorectal cancer remains a medical focus and challenging topic.
In 1972, schistosome eggs were discovered in the liver and rectum tissue of a female corpse from the Western Han Dynasty unearthed in Mawangdui, Changsha, Hunan Province, confirming that schistosomiasis has a history of at least 2,100 years [23]. The main harm of schistosomes to the human body is tissue damage caused by eggs; long-term chronic inflammation from egg deposition produces oxygen free radicals and other substances that can damage DNA. It has been reported that schistosome is a high-risk factor for colorectal cancer [17, 24].
In clinical work, we observed white induration on the abdominal wall during surgery that could not be ruled out as metastasis of colorectal cancer. However, Rapid pathology during surgery showed calcified schistosome eggs, indicating that schistosomiasis can affect the judgment and decision-making of surgeons. In this study, we analyzed the clinical and prognostic data of colorectal cancer patients with chronic schistosomiasis, and investigated the effect of schistosomiasis on the prognosis of colorectal cancer patients.
This study observed a geographic clustering of CRCS+ patients in the Dongting Lake and its tributaries area, particularly in coastal cities such as Yueyang, Yiyang, and Changde. The results suggest that there is a tendency for CRCS+ patients to cluster along river and lake regions.
This study observed that the majority of CRCS+ patients were diagnosed at stage I and II, accounting for 61.7% of cases. In contrast, only 48.8% of colorectal cancer patients without schistosomiasis were at stage I and II. This may be because chronic inflammation caused by schistosomiasis may contribute to tumor development while also inhibiting lymph node metastasis, leading to a higher proportion of early-stage tumors.
In terms of age distribution, the average age of CRCS+ patients was 66.13 ± 9.23 years while the average age of CRCS− patients was 58.35 ± 12.07 years. The average age of CRCS+ patients was older and the proportion of elderly patients (≥ 60 years old) was higher (84.0% vs. 49.3%). This may be attributed to the fact that it takes a long time for schistosomiasis to develop into colorectal cancer.
The preoperative blood routine examination results of both CRCS+ and CRCS− patients were within the normal range, and there was no significant difference between the two groups. Previous studies have found that patients with parasitic diseases often exhibit an increased eosinophil count in their blood. However, in our study, no significant difference was observed in the eosinophil count between CRCS+ and CRCS− patients, which may be attributed to the inactivation of schistosome eggs due to calcification.
The preoperative liver function test results indicated that the level of aspartate aminotransferase in CRCS+ patients was significantly higher than that in CRCS- patients, while the other liver function test indicators showed no significant difference between the two groups. Moreover, a higher proportion of CRCS+ patients had liver cirrhosis, but the differences in portal hypertension and Child-Pugh classification between the two groups were not statistically significant, likely due to the limited sample size in this study. Further studies with larger sample sizes are needed to confirm these findings. The differences in liver function between the two groups may be attributed to the fact that in patients with schistosomiasis, schistosome eggs can not only reside in the intestine but also travel through the bloodstream to the liver, resulting in liver damage.
Previous studies have reported that CA125 levels in CRCS+ patients were significantly higher than in CRCS− patients [25]. However, in our study, there was no significant difference in preoperative CA125 levels between the two groups. Similarly, preoperative levels of other tumor markers, including CA199, CEA, and AFP, were not significantly different between the two groups. It is important to note that these results may be affected by the small sample size of our study. Nonetheless, our findings suggest that relying solely on tumor markers may not be sufficient for the early detection of colorectal cancer in patients with schistosomiasis. Further studies with larger sample sizes are needed to validate our findings.
In this study, it was found that the positive rate of preoperative fecal monoclonal occult blood test in CRCS+ patients was significantly lower than that in CRCS- patients, indicating that the fecal monoclonal occult blood test is more likely to yield false negative results in patients with schistosomiasis. Therefore, colonoscopy should be performed as a screening tool for patients with schistosomiasis in medical institutions where conditions permit. Furthermore, blood type analysis revealed that there were more individuals with type B blood and fewer with type O blood in the CRCS+ patient group. This observation led us to speculate that type B individuals may be more susceptible to schistosomiasis, while type O individuals may be less prone to the disease.
By analyzing preoperative colonoscopy reports, this study compared the probability of multiple colonic polyps between CRCS+ and CRCS− patients. There was no significant difference in the probability of multiple colonic polyps between the two groups; that is, long-term chronic inflammation caused by schistosome eggs did not increase the probability of polyps. Moreover, preoperative CT images revealed that some CRCS+ patients had intestinal calcification, which was not observed in any of the CRCS− patients. Thus, schistosome egg calcification may be considered as one of the characteristics of CRCS+ patients.
This study revealed that the overall survival rate of CRCS+ patients was significantly lower than that of CRCS− patients and that schistosomiasis was an independent risk factor for the prognosis of colorectal cancer. It is unclear why chronic schistosomiasis leads to a worse prognosis for colorectal cancer. We speculate that the pathogenesis of long-term chronic inflammation in colorectal cancer differs from the traditional pathogenesis of colorectal cancer, leading to differences in prognosis. According to current guidelines, combination chemotherapy with two drugs is recommended for patients with TNM stage II colorectal cancer and high-risk factors, such as T4, poor histological differentiation, nerve or vessel invasion, preoperative tumor perforation or intestinal obstruction, unclear surgical margin or insufficient safe distance of resection margin, and less than 12 resected lymph nodes. Given the results of this study, we believe that schistosomiasis is also a high-risk factor for recurrence and metastasis of colorectal cancer and whether combined chemotherapy is necessary for stage II colorectal cancer patients with chronic schistosomiasis needs to be further confirmed by a large amount of data.
Limitations of this study include: 1) Colorectal cancer complicated with chronic schistosomiasis is a rare disease, so the sample size is relatively small; 2) The time span of cases in this study is long and the follow-up time of some cases is short; 3) this study is only an observational study, and therefore, further in-depth study on the mechanism is needed.
Compared to CRCS− patients, CRCS+ patients exhibited distinct clinicopathological features such as regional clustering, advanced age, severe liver function impairment, and a lower positive rate of fecal monoclonal blood tests. Calcification is identified as a characteristic feature of CRCS+ patients. Moreover, the study found that colorectal cancer patients with chronic schistosomiasis have a worse overall survival and that schistosomiasis is an independent risk factor for colorectal cancer.
colorectal cancer patients with chronic schistosomiasis
colorectal cancer patients without chronic schistosomiasis
overall survival.
Ethics approval and consent to participate
All methods were carried out in accordance with relevant guidelines and regulations. The studies involving human participants were reviewed and approved by the Research Ethics Committee of Xiangya Hospital, Central South University (Project No. 202212297). The participants provided their written informed consent to participate in this study.
Consent for publication
Not applicable.
Availability of data and materials
Data cannot be shared publicly because of ethics policy at Xiangya Hospital, Central South University, whereby any new analyses require Research Ethics Committee approval (Contact via Email: [email protected]).
Competing interests
The authors declare that they have no competing interests.
Funding
This study was supported by the Nature Scientific Foundation of China (Grant No. 82273077) and the Natural Science Foundation of Hunan Province (Grant No. 2022JJ40799). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Authors' contributions
HG, YL and HP conceived and designed the study. HG and XL were responsible for collecting the data, writing the first draft, and editing the manuscript. LZ, ZT were responsible for analyzing the data and revising the manuscript. All authors read and approved the final manuscript.
Acknowledgements
We thank all patients who agreed to participate in the study.