Colorectal cancer and Blastocystis sp. infection.

BACKGROUND: Blastocystis sp. is a common intestinal protozoan found worldwide. Based on gene analysis, 17 subtypes (STs, ST1-ST17) have been identified, 9 of which have been isolated from humans. Differences in clinical consequences may depend on differences among the STs. Here, we evaluated the prevalence of Blastocystis sp. in patients with colorectal cancer (CRC) compared to a control group and assessed the relationships between Blastocystis sp. infection and sex; age; and CRC grade, stage, and location. METHODS: The study included 107 CRC patients (41 women and 66 men, median age 65 years); 124 subjects without colorectal cancer or a history of oncological disease comprised the control group (55 women and 69 men, median age 63). Stool samples were collected from patients before oncological treatment and examined using light microscopy (iodine-stained smear). Additionally, PCR-based identification of Blastocystis sp. was performed in 95 stool samples from CRC patients and 76 stool samples from the control group. RESULTS: Light microscopy showed that the prevalence of Blastocystis sp. was significantly higher in CRC patients than in the control group (12.15% and 2.42%, respectively; p = 0.0041). Multivariate analysis showed that the odds of Blastocystis sp. infection were fivefold higher in the CRC group than in the control group. PCR-based molecular examinations demonstrated that the proportion of patients infected with Blastocystis sp. was significantly higher in the CRC group than in the control group (12.63% and 2.63%, respectively; p = 0.023). The predominant ST in the CRC group was ST3, detected in nine patients (75%), followed by ST1 (2 patients, 16.7%) and ST2 (1 patient, 8.3%). No association was found between Blastocystis sp. infection and age, sex, or CRC stage, grade, or location. CONCLUSIONS: The results showed that CRC was associated with an increased risk of opportunistic Blastocystis sp. infection, even before oncological treatment. To the best of our knowledge, this is the first report estimating the prevalence of Blastocystis sp. infection in CRC patients before oncological treatment in Europe.

Comparison of non-schistosomal colorectal cancer and schistosomal colorectal cancer.

AIM: The purpose of this study was to compare clinicopathological features of patients with non-schistosomal and schistosomal colorectal cancer to explore the effect of schistosomiasis on colorectal cancer (CRC) patients' clinical outcomes. METHODS: Three hundred fifty-one cases of CRC were retrospectively analyzed in this study. Survival curves were constructed by using the Kaplan-Meier (K-M) method. Univariate and multivariate Cox proportional hazard regression models were performed to identify associations with outcome variables. RESULTS: Colorectal cancer patients with schistosomiasis (CRC-S) were significantly older (P < 0.001) than the patients without schistosomiasis (CRC-NS). However, there were no significant differences between CRC-S and CRC-NS patients in other clinicopathological features. Schistosomiasis was associated with adverse overall survival (OS) upon K-M analysis (P = 0.0277). By univariate and multivariate analysis, gender (P = 0.003), TNM stage (P < 0.001), schistosomiasis (P = 0.025), lymphovascular invasion (P = 0.030), and lymph nodes positive for CRC (P < 0.001) were all independent predictors in the whole cohort. When patients were stratified according to clinical stage and lymph node metastasis state, schistosomiasis was also an independent predictor in patients with stage III-IV tumors and in patients with lymph node metastasis, but not in patients with stage I-II tumors and in patients without lymph node metastasis. CONCLUSION: Schistosomiasis was significantly correlated with OS, and it was an independent prognostic factor for OS in the whole cohort. When patients were stratified according to clinical stage and lymph node metastasis state, schistosomiasis was still an independently unfavorable prognosis factor for OS in patients with stage III-IV tumors or patients with lymph node metastasis.

The prognostic role of c-MYC amplification in schistosomiasis-associated colorectal cancer.

OBJECTIVE: The purpose of this study was to explore the prognostic role of c-MYC amplification in colorectal cancer, particularly in schistosomiasis-associated colorectal cancer. METHODS: Three hundred and fifty four cases of colorectal cancer, which were from Qingpu Branch of Zhongshan Hospital affiliated to Fudan University, were retrospectively analyzed in a tissue microarray (TMA) format, with fluorescence in situ hybridization (FISH) assay and immunohistochemistry (IHC). RESULTS: c-MYC gene amplification was found in 14.1% (50 out of 354) of patients with colorectal cancer and was correlated with old age (P = 0.028), positive lymph node metastasis (P = 0.004) and advanced stage tumors (P = 0.002). The overexpression of c-MYC was closely associated with the amplification status (P = 0.023). Kaplan-Meier survival curves for overall survival (OS) showed a statistically significant difference for patients with c-MYC amplification in full cohort of colorectal cancer, stage III-IV set and patients with lymph node metastasis (P = 0.002, 0.034, 0.012, respectively). Further analysis found c-MYC amplification associated with poorer survival in the subgroup of colorectal cancer with schistosomiasis (CRC-S, P < 0.001), but not in colorectal cancer without schistosomiasis (CRC-NS, P = 0.155). By multivariate analysis, c-MYC amplification was an independent poor-prognostic factor in CRC-S set (P = 0.046). CONCLUSIONS: Our study firstly found c-MYC amplification could predict poor prognosis in schistosomiasis-associated colorectal cancer, but not in colorectal cancer without schistosomiasis.

Schistosoma japonicum-Associated Colorectal Cancer: A Review.

Schistosoma japonicum is a digenetic blood fluke that has been implicated in the carcinogenesis of several human malignancies, notably liver and colorectal cancer (CRC). Schistosoma japonicum-associated colorectal cancer (SACC) is a distinct subtype with biological behavior analogous to colitis-induced CRC. The clinicopathological characteristics of SACC include young age at diagnosis, predominance among males, a strong predilection for the sigmoid colon and rectum, multifocal distribution, frequent mucinous histology, and poor prognosis. In addition to chronic inflammation, immunomodulation, and schistosomal toxins, bacterial coinfection appears to play an important role in the carcinogenic process. The present review provides the most recent updates on epidemiology, pathobiology, and clinical and prognostic features pertaining to SACC.

Intestinal helminths and protozoan infections in patients with colorectal cancer: prevalence and possible association with cancer pathogenesis.

The purpose of the present study was to determine the prevalence of intestinal helminths and protozoa in colorectal cancer (CRC) patients and to evaluate the possible association between the prevalence and CRC pathogenesis. A total of 200 CRC patients and 200 residents of Tashkent, who had no complaints related to the gastrointestinal tract, were examined by triple coproscopy using a concentration method and estimations of protozoan infection intensity. Of the CRC patients tested, 144 were classified as T1-4N0M0 (without metastases) and 56 were classified as T1-4N1-2M0-1 (with metastases). Parasitological examination was performed during CRC diagnosis before and after surgery and chemotherapy. A significantly higher prevalence of Blastocystis sp., Chilomastix mesnili, Jodamoeba butschlii, and Endolimax nana was found in CRC patients than in the control population (p < 0.0001), amounting to 80, 20, 22.5, and 11.5%, respectively. The high prevalence of Blastocystis sp., as well as the patterns of infection intensity, was stable at all stages of examination. The ratio of the number of CRC patients with and without Blastocystis sp. in the T1-4N0M0 and T1-4N1-2M0-1 groups amounted to 3.3 and 7.0, respectively. The ratios for C. mesnili, E. coli, J. butschlii, and E. nana in both groups were 0.2 and 0.2, 0.07 and 0.07, 0.3 and 0.16, and 0.18 and 0.01, respectively. The prevalence of helminths and Giardia lamblia in CRC patients and the control population was not significantly different. Taken together, these data indicate a possible role for Blastocystis sp. in CRC pathogenesis. Diagnosis, treatment, and further observation of patients with Blastocystis sp. are necessary at all stages of CRC, including during diagnosis and before and after surgery and chemotherapy.

Potential Application of Eicosapentaenoic Acid Monoacylglyceride in the Management of Colorectal Cancer.

BACKGROUND: There is increasing evidence that marine omega-3 oils are involved in the reduction of cancer risk and progression. However, the anticancer effect of omega-3 monoglyceride on colorectal cancer has yet to be assessed. The goal of this study was to evaluate the anti-cancer effects of eicosapentaenoic acid monoglyceride (MAG-EPA) in HCT116 colorectal carcinoma cells. METHODS: The effect of MAG-EPA was evaluated in vitro on HCT116 cells and in vivo on mouse model of HCT116 xenograft. RESULTS: Our data reveal that MAG-EPA decreased cell proliferation and induced apoptosis in HCT116 cells. In a xenograft mouse model, daily per os administration of MAG-EPA reduced tumor growth. Furthermore, MAG-EPA treatments decreased EGFR, VEGFR, and AKT activation pathways and reduced VEGF and HIF1α expression levels in tumors. CONCLUSION: MAG-EPA may promote apoptosis and inhibit growth of tumors by suppressing EGFR and VEGFR activation pathways. Altogether, these data provide new evidence regarding the mode of action of MAG-EPA in colorectal cancer cells.

Colorectal cancer in a patient with intestinal schistosomiasis: a case report from Kilimanjaro Christian Medical Center Northern Zone Tanzania.

BACKGROUND: Colorectal cancer associated with chronic intestinal schistosomiasis has been linked with the chronic inflammation as a result of schistosomal ova deposition in the submucosal layer of the intestine. Among all species Schistosoma japonicum has been more linked to development of colorectal cancer as compared to Schistosoma mansoni due to absence of population-based studies to support the association. Despite the weak evidence, some cases have been reported associating S. mansoni with development of colorectal cancer. CASE PRESENTATION: We report a patient who presented to us as a case of intestinal obstruction and found to have a constrictive lesion at the sigmoid colon at laparotomy, then later found to have colorectal cancer with deposited S. mansoni ova at histology. CONCLUSION: Given the known late complications of schistosomiasis, and as S. mansoni is endemic in some parts of Tanzania, epidemiological studies are recommended to shed more light on its association with colorectal cancer.

Clinicopathological characteristics and prognosis of schistosomal colorectal cancer.

AIM: The aim of the present study was to investigate the clinicopathological characteristics and prognostic factors of schistosomal colorectal cancer. METHOD: A total of 74 consecutive schistosomal colorectal cancer patients who underwent curative surgery from July 2009 to July 2012 were included in this study. The clinical and pathological characteristics of all 74 patients were analysed and univariate and multivariate analyses were performed. This study demonstrated positive correlations between the site of deposition of schistosomal eggs and certain essential variables. RESULTS: Depositional site of schistosome eggs, carcinoembryonic antigen (CEA) level and the pathological N and T stages were statistically significantly correlated with overall survival (OS). The pathological T stage and the CEA level were independent prognostic factors for OS. The site of deposition of schistosome eggs was positively correlated with the T and N stages, tumour size, the CEA level and the resection margins. CONCLUSIONS: Schistosome eggs might be associated with tumorigenesis. The site of deposition of schistosome eggs was statistically significantly correlated with OS but it was not an independent prognostic factor for OS. It was, however, correlated with the depth of the tumour. The presence of schistosoma eggs at the margin did not affect the patient's prognosis or anastomotic healing. The existing standard surgical approach was equally applicable to schistosomal colorectal cancer. It was not necessary to expand the scope of surgical resection.

Advantage of using colonic washouts for Blastocystis detection in colorectal cancer patients.

BACKGROUND: There have been previous studies associating microorganisms to cancer and with our recent findings of Blastocytsis antigen having a higher in vitro proliferation of cancer cells strengthens the suspicion. Collecting faecal samples alone to associate this parasite with cancer may not be accurate due to the phenomenon of irregular shedding and the possible treatment administrated to the cancer patients. Hence, this become the basis to search for an alternate method of sample collection. Colonic washout is an almost complete washed up material from colon and rectum which includes various microorganisms such as Blastocystis and other lodged material within the villi. The detection of parasite in colonic washouts will give a better reflection on the association between Blastocystis and CRC. METHODS: Blastocytsis detection was made by in vitro culture method using Jones' medium, formal ether concentration technique and conventional polymerase chain reaction (PCR) on faecal samples and colonic washouts of 204 CRC patients from colonoscopy procedure. Faecal samples and colonic washouts from 221 normal individuals served as control. RESULTS: We observed an increased detection of Blastocystis using colonic washouts (n = 53, 12.47%) than faecal samples (n = 26, 6.12%). Eleven faecal samples showed positive results for Blastocystis which were also found in colonic washouts using the PCR technique. This study for the first time showed a significant Blastocystis infection among CRC patients (n = 43, 21.08%) compared to the asymptomatic normal individuals (n = 22, 9.95%). Blastocystis subtype 3 infection was found to be significantly more prevalent (n = 26, 12.75%) compared to other subtypes namely subtype 1: n = 9 (4.41%), subtype 2: n = 1 (0.49%), subtype 5: n = 1 (0.49%) and mixed subtype: n = 6 (2.94%) among the CRC patients. CONCLUSION: The study showed that colonic washouts provide a better alternative for Blastocystis detection in CRC patients compared to faecal samples as this prevents treatment regime and the phenomenon of irregular shedding from influencing the detection results obtained from faecal samples.

[Expression of vascular growth factors in intestinal tissues in colorectal carcinoma patients with schistosomiasis japonica].

OBJECTIVE: To investigate the differences of mRNA quantitation and protein expression of vascular growth factors including platelet-derived endothelial cell growth factor (PD-ECGF) and vascular endothelial growth factor (VEGF) in intestinal tissues in colorectal carcinoma patients with and without schistosomiasis. METHODS: Thirty colorectal carcinoma patients with schistosomiasis and 30 colorectal carcinoma patients without schistosomiasis were included in this study. The mRNA quantitation and protein expression of PD-ECGF and VEGF in the normal tissue, peri-carcinoma tissue as well as carcinoma tissue obtained from surgical specimens were detected by qRT-PCR and Western blot. RESULTS: The mRNA relative quantitations of PD-ECGF in normal tissue, peri-carcinoma tissue and carcinoma tissue in the colorectal carcinoma patients with schistosomiasis were 1.726, 1.766 and 2.729 times to those in the colorectal carcinoma patients without schistosomiasis, respectively. The corresponding ones of VEGF were 2.138, 1.831 and 3.376 times, respectively. The protein expression levels of PD-ECGF and VEGF in normal tissue, peri-carcinoma tissue and carcinoma tissue were higher in the colorectal carcinoma patients with schistosomiasis than in the colorectal carcinoma patients without schistosomiasis. CONCLUSIONS: The expressions of vascular growth factors including PD-ECGF and VEGF are higher in the colorectal carcinoma patients with schistosomiasis than in the colorectal carcinoma patients without schistosomiasis. Therefore, schistosomiasis may be one of the risk factors of colorectal cancer.

Effects of symptomatic and asymptomatic isolates of Blastocystis hominis on colorectal cancer cell line, HCT116.

The pathogenesis of Blastocystis hominis in human hosts has always been a matter of debate as it is present in both symptomatic and asymptomatic individuals. A recent report showed that B. hominis isolated from an asymptomatic individual could facilitate the proliferation and growth of existing cancer cells while having the potential to downregulate the host immune response. The present study investigated the differences between the effects of symptomatic and asymptomatic derived solubilized antigen of B. hominis (Blasto-Ag) on the cell viability and proliferation of colorectal cancer cells. Besides that, the gene expression of cytokine and nuclear transcriptional factors in response to the symptomatic and asymptomatic B. hominis antigen in HCT116 was also compared. In the current study, an increase in cell proliferation was observed in HCT116 cells which led to the speculation that B. hominis infection could facilitate the growth of colorectal cancer cells. In addition, a more significant upregulation of Th2 cytokines observed in HCT116 may lead to the postulation that symptomatic Blasto-Ag may have the potential in weakening the cellular immune response, allowing the progression of existing tumor cells. The upregulation of nuclear factor kappa light chain enhancer of activated B cells (NF-κB) was observed in HCT116 exposed to symptomatic Blasto-Ag, while asymptomatic Blasto-Ag exhibited an insignificant effect on NF-κB gene expression in HCT116. HCT116 cells exposed to symptomatic and asymptomatic Blasto-Ag caused a significant upregulation of CTSB which lead to the postulation that the Blasto-Ag may enhance the invasive and metastasis properties of colorectal cancer. In conclusion, antigen isolated from a symptomatic individual is more pathogenic as compared to asymptomatic isolates as it caused a more extensive inflammatory reaction as well as more enhanced proliferation of cancer cells.

Colorectal carcinoma associated with schistosomiasis: a possible causal relationship.

The association between schistosomiasis and colorectal malignancy has long been suggested in the literature, but it is not uniformly accepted. In the Far East, considerable evidence supports an etiological link between Schistosoma japonicum and colorectal cancer. However, the available data regarding the role of Schistosoma mansoni in colorectal carcinogenesis are conflicting and most often do not show causality. We report on a patient with sigmoid colonic cancer coexisting with schistosomiasis, and we provide a comprehensive review of the literature regarding the epidemiology and pathobiology of this association.

Solubilized antigen of Blastocystis hominis facilitates the growth of human colorectal cancer cells, HCT116.

Blastocystis hominis is one of the most common intestinal protozoan parasites in humans, and reports have shown that blastocystosis is coupled with intestinal disorders. In the past, researchers have developed an in vitro model using B. hominis culture filtrates to investigate its ability in triggering inflammatory cytokine responses and transcription factors in human colonic epithelial cells. Studies have also correlated the inflammation by parasitic infection with cancer. The present study provides evidence of the parasite facilitating cancer cell growth through observing the cytopathic effect, cellular immunomodulation, and apoptotic responses of B. hominis, especially in malignancy. Here we investigated the effect of solubilized antigen from B. hominis on cell viability, using peripheral blood mononuclear cells (PBMCs) and human colorectal carcinoma cells (HCT116). The gene expressions of cytokines namely interleukin 6 (IL-6), IL-8, tumor necrosis factor alpha, interferon gamma, nuclear factor kappa light-chain enhancer of activated B cells (a gene transcription factor), and proapoptotic genes namely protein 53 and cathepsin B were also studied. Results exhibited favor the fact that antigen from B. hominis, at a certain concentration, could facilitate the growth of HCT116 while having the ability to downregulate immune cell responses (PBMCs). Therefore, there is a vital need to screen colorectal cancer patients for B. hominis infection as it possesses the ability to enhance the tumor growth.

Colorectal cancer in a population with endemic Schistosoma mansoni: is this an at-risk population?

PURPOSE: Chronic infection with schistosomiasis has been clearly associated with the development of bladder cancer, and infestation is associated with a high incidence of colorectal cancer in endemic populations. Despite this association, the potential role of alterations in tumor suppressor genes colorectal cancers has never been evaluated in an endemically infected population. The aim of this paper was to compare histopathologic and genetic changes in schistosomal colitis-associated colorectal cancer (SCC) with colorectal cancer in a group of patients from the same population not affected by the disease (NDCC). MATERIALS AND METHODS: Sixty patients were included in this study: SCC-40, NDCC-20. Data collected included age, sex, clinical presentation, presence of synchronous tumors, histopathology, and clinical stage. p53, DCC (deleted in colorectal cancer gene), and mismatch repair genes (MLH1 and MSH2) were studied using immunohistochemical staining. RESULTS: Patients with SCC were significantly younger than the NDCC group (34.52+/-11.22 years vs 50.73+/-12.75 years, p=0.02). Mucinous adenocarcinoma occurred significantly more frequently in SCC (35 vs 10%, p=0.02). SCC tumors were more frequently stage III or IV, and significantly more synchronous tumors were present in the affected group (SCC-8/40 vs NDCC-1/20, p=0.05). p53 staining was far more frequent in SCC (SCC-32/40 vs NDCC-8/20, p=0.006). DCC expression was similar in two groups. There were only four cases, three in SCC and one in NDCC, that showed microsatellite instability. CONCLUSION: The data suggest that schistosomal colitis is more commonly associated with earlier onset of multicentric colorectal cancer, high percentage of mucinous adenocarcinoma, and presents at an advanced stage. The identification of a higher incidence of altered p53 expression in the SCC group raises the possibility of an association between schistosomiasis and alterations in p53 activation as an inciting event in colorectal cancer development.

Acute colorectal obstruction treated by means of transanal drainage tube: effectiveness before surgery and stenting.

OBJECTIVES: The aim of this study was to clarify the usefulness of the management of acute colorectal obstruction using a transanal drainage tube before surgery or stenting. METHODS: Fifty-four patients (34 males and 20 females, aged 46-94 yr, mean = 69.7) treated between May 1998 and March 2004 for acute colorectal obstruction were identified in a colorectal obstruction database, and their clinical and radiological features were reviewed. Based on abdominal computed tomography findings, urgent colonoscopy was performed. Subsequently, endoscopic decompression using a Dennis Colorectal Tube (DCT) was attempted. RESULTS: Endoscopic decompression using the DCT was technically successful in 52 of 54 patients (96.3%). The site of obstruction was the cecum in 4, the ascending colon in 2, the transverse colon in 7, the descending colon in 11, the sigmoid colon in 18, and the rectum in 12. The etiology of obstruction was primary colorectal carcinoma in 45, non-colonic metastatic carcinoma in 4, postoperative obstruction in 4, and retrograde intussusception in 1. Following adequate cleansing of the colon, 44 patients underwent a one-stage surgery after 7+/- 3 days (SD; range, 4-10 days). Stenting was successfully used as the final palliative treatment in 4. The use of the DCT alone relieved postoperative stenosis (3 patients) and retrograde intussusception (Prognosis in patients with obstructing colorectal carcinoma. Am J Surg 1982;143:742-7). During these treatments, perforation occurred in one patient with postoperative stenosis of the cecum. CONCLUSIONS: Management of acute colorectal obstruction using the DCT was found to be effective and safe, irrespective of the site or etiology of the obstruction. Therefore, this procedure should be considered as a primary method for decompression of the obstructed colon before considering surgery or stenting.

Phase I and pharmacokinetic study of the polyamine synthesis inhibitor SAM486A in combination with 5-fluorouracil/leucovorin in metastatic colorectal cancer.

PURPOSE: The purpose of our study was to determine the maximum-tolerated dose, dose-limiting toxicity, safety profile, and pharmacokinetics of the polyamine synthesis inhibitor SAM486A given in combination with 5-fluorouracil/leucovorin (5-FU/LV) in cancer patients. EXPERIMENTAL DESIGN: Patients with advanced colorectal cancer were treated with 5-FU [bolus (400 mg/m(2)) followed by a 22-h infusion (600 mg/m(2))] and LV (200 mg/m(2)) and escalating doses of SAM486A, 1-3-h infusion daily for 3 days. Plasma sampling was performed to characterize the pharmacokinetics and pharmacodynamics of the combination RESULTS: Twenty-seven patients with metastatic colorectal cancer and 1 with pseudomyxoma peritonei were treated. Twenty-six patients received SAM486A in the combination at doses ranging from 25 to 150 mg/m(2)/day. Dose-limiting toxicity consisting of fatigue grade 3 was seen at 150 mg/m(2)/day. Other adverse events included neutropenia, hand and foot syndrome, nausea, vomiting, diarrhea, and constipation. Fifteen of 26 patients evaluable for best response according to the Southwest Oncology Group criteria achieved a partial response [8 (30%) of 26] or stable disease [9 (35%) of 26]. SAM486A did not influence the pharmacokinetics of 5-FU, and SAM486A clearance was similar to that when used as a single agent. CONCLUSIONS: The novel molecular agent SAM486A is tolerable and safe in combination with a standard 5-FU regimen in patients with advanced colorectal cancer. The dose of SAM486A recommended for additional studies with this combination is 125 mg/m(2)/day. A disease-directed evaluation of SAM486A using this regimen is warranted.

Histological classification of schistosomal egg induced polyps of colon and their clinical significance. An analysis of 272 cases.

272 cases of schistosomal egg induced polyps collected from mass-screening for colorectal carcinoma in Jiashan County were divided into 3 types: fibrous type (FT), mixed type (MT) and epithelial proliferative type (ET). The ET was characterized by crypt elongation, hypertrophy, variation in size, disorderly arrangement, as well as the high percentage of atypical hyperplasia (64.9%). The coexistence and transition between inflammatory reactive hyperplastic and neoplastic crypts were noticed. By HID/AB staining, sialomucins were increased in ET, CEA and PNA receptors detected by the ABC method were present in 18/20 and 6/18 of ET respectively. The mucin expression of ET was similar to that of adenomas. It is likely that a spectrum of ET, atypical hyperplasia and adenoma may exist. We suggest that the patients with ET, especially those with atypical hyperplasia, should be regarded as "risk group", and close follow-up is needed.