Risk Of Colorectal Carcinoma Research Articles

Hereditary, environmental, and dietary risk factors of colorectal cancer: a case-control study in the Algerian East.

Colorectal carcinoma (CRC) is the second most common cancer diagnosed in Algeria. The incidence and the mortality rate of CRC have increased so that the nation now ranks third in Africa in both these variables. Many environmental and genetic factors are suspected to play an important role in the development of the disease. This study aimed to identify the risk factors for CRC in Algeria. We performed a case-control study in five Medical Oncology Services in this region: Tebessa, Batna, Annaba, Setif, and Constantine, from 2016 to 2019. Altogether, 200 patients diagnosed with CRC and 200 age-matched controls without any diagnosis of cancer were included. Study participants were interviewed about environmental, dietary, and hereditary risk factors, i.e., family history of cancer, using a questionnaire. Results showed a significant association between high educational level and a decreased risk of CRC. Diagnoses of any cancer or of CRC in first-degree or in second- or third-degree relatives also were significantly associated with CRC risk. Occupational exposures showed a significant link with an increased risk of CRC, as did obesity, alcohol consumption, and passive smoking. Yogurt, cereals, sugar, butter, and margarine consumption were significant protective factors, while cheese, dried fruits, red meat, juice, and fizzy drink consumption was associated with increased risk. Our findings suggest a benefit of public health campaigns to enhance awareness about CRC and to encourage healthy dietary choices and avoidance of non-dietary risk factors.

Correlation of Carcinoma Percentage (CP) in Colorectal Adenocarcinoma with Several Clinical Pathological Aspects in Anatomical Pathology Department Faculty of Medicine Universitas Indonesia/Cipto Mangunkusumo Hospital Jakarta in Year 2012-2013

Background: Colorectal carcinoma is malignant tumour of the large intestinal epithelial, where more than 90% of colorectal carcinoma is adenocarcinoma. Desmoplastic stroma in primary tumour holds an important role in tumour development process. Mesker et al described carcinoma percentage (CP) evaluation in routine preparations with Haematoxylin-eosin (HE) staining as one of the prognostic factors.Method: This retrospective study was performed by collecting forms and slides of colorectal carcinoma resection cases from the archives of Anatomical Pathology Department FMUI-CMGNH in 2 years period (2012-2013). Collection of clinical data and re-evaluation of HE slides by 2 people which were the writer and supervisor were performed to determine CP value by observing the comparison between tumour percentage and desmoplastic stroma.Results: We included 92 cases of colorectal adenocarcinoma within those 2 years period (2012-2013). Comparison of total cases between male and female was 3:2, age 40 years old were the most commonly found; in regard to location in the colon, most were found in the left side compared to the right side of the colon with the ratio of 3:7. Tumour histological grading with good differentiation were the most commonly found and most pT value being found were pT3; most lymph node involvement was N1. The most CP value attained in every parameter was CP-Low.Conclusion: Carcinoma percentage (CP) which was divided as CP-High and CP-Low could be used as a prognostic factor. In this study, we found more cases of CP-Low compared to CP-High, either based on sex, age, location, degree of differentiation, pT value, or even lymph node involvement. CP-Low which showed worse prognosis could also be used as a marker of patients who were at higher risk of colorectal carcinoma.

Analysis of Killer Immunoglobulin-Like Receptor Genes in Colorectal Cancer.

Natural killer cells (NK cells) play a major role in the immune response to cancer. An important element of NK target recognition is the binding of human leucocyte antigen (HLA) class I molecules by killer immunoglobulin-like receptors (KIRs). Colorectal carcinoma (CRC) is one of the most common types of inflammation-based cancer. The purpose of the present study was to investigate the presence of KIR genes and HLA class I and II alleles in 1074 CRC patients and 1272 controls. We imputed data from single-nucleotide polymorphism (SNP) Illumina OncoArray to identify associations at HLA (HLA–A, B, C, DPB1, DQA1, DQB1, and DRB1) and KIRs (HIBAG and KIR*IMP, respectively). For association analysis, we used PLINK (v1.9), the PyHLA software, and R version 3.4.0. Only three SNP markers showed suggestive associations (p < 10−3; rs16896742, rs28367832, and rs9277952). The frequency of KIR2DS3 was significantly increased in the CRC patients compared to healthy controls (p < 0.005). Our results suggest that the implication of NK cells in CRC may not act through allele combinations in KIR and HLA genes. Much larger studies in ethnically homogeneous populations are needed to rule out the possible role of allelic combinations in KIR and HLA genes in CRC risk.

Traditional serrated adenoma-like lesions in patients with inflammatory bowel disease

Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal carcinoma. The significance of serrated lesions resembling traditional serrated adenoma (TSA) in IBD patients is unclear. In this retrospective study, we analyzed 52 TSA-like lesions arising in 30 IBD patients and diagnosed in colectomy or endoscopic specimens. The 27 colectomy lesions presented predominantly as ill-defined areas with granular appearance, with a median size of 15 mm, located throughout the large bowel and associated with synchronous advanced colorectal lesions in 58%. Low-grade serrated dysplasia was present in 56%, high-grade serrated dysplasia in 37%, and TSA-type cytology in 7%. Increased Ki-67 immunostaining and abnormal p53 expression were identified in 96% and 48%, respectively; 74% had a KRAS mutation, and 4% had a BRAF mutation. Endoscopically resectable TSA-like lesions were all discrete polypoid lesions, smaller in size (median 9 mm), predominantly in the distal large bowel, with an adjacent precursor polyp in 24%, and associated with synchronous and metachronous advanced colorectal lesions in 6%. Most (92%) show TSA-type cytology. p53 overexpression was present in 4%, KRAS mutation in 41%, and BRAF mutation in 32%. None of the 52 TSA-like lesions demonstrated loss of MLH1 or SATB2 expression by immunohistochemistry. On follow-up, 4 patients were diagnosed with colorectal carcinoma or high-grade adenomatous IBD-associated dysplasia. None of the patients with lesions showing TSA-type cytology only developed an advanced lesion. Our findings suggest that some TSA-like lesions, essentially from colectomy, may represent a form of IBD-associated dysplasia associated with an increased risk of advanced neoplasia.

Antibiotic exposure and the risk of colorectal adenoma and carcinoma: a systematic review and meta-analysis of observational studies.

The Incidence of colorectal cancer (CRC) is increasing, and evidence suggests that maladaptation of the bowel microbiome may be associated with colorectal carcinogenesis. Consumption of antibiotics may cause imbalance of the bowel microbiome but research assessing an association between antibiotic exposure and CRC is inconsistent. The aim of this systematic review and meta-analysis was to appraise and synthesize the available evidence. The MEDLINE, EMBASE and CINAHL databases were searched for published observational studies. We included eight studies of 3408312 patients. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for the odds of CRC following antibiotic exposure were estimated. Sensitivity analyses were performed according to exposure definition, study design and risk of bias. A weak association between antibiotic exposure and CRC was demonstrated when exposure was assessed cumulatively by the number of prescriptions (OR 1.204, 95% CI 1.097-1.322, P<0.001) or duration of antibiotic exposure (OR 1.168, 95% CI 1.087-1.256, P<0.001). Antibiotic exposure assessed as a binary variable demonstrated no association with CRC. The findings suggest a weak association between cumulative antibiotic consumption and risk of CRC but no causal conclusions can be made. Limitations include the heterogeneity and quality of the available research, particularly with regard to measurement of antibiotic exposure.

Epidemiology, risk of malignancy and patient survival in primary sclerosing cholangitis: a population-based study in Finland

Background: There are only a few and mostly small population-based epidemiological studies of primary sclerosing cholangitis (PSC).Objective: We aimed to estimate prevalence and incidence rates of PSC, and survival and malignancy risk for PSC patients in a large population-based study.Methods: We retrieved 632 PSC patients from 1990 to 2015 in the Hospital District of Helsinki and Uusimaa (HUS), comprising 29% of the Finnish population. Mortality information of the PSC patients was obtained from the national Population Registry, malignancy information from the Finnish Cancer Registry and the causes of death from the Statistics Finland. Standardized incidence ratio and standardized mortality ratio (SMR) were calculated for predefined malignancy types.Results: The crude incidence of PSC in the HUS area was 1.58/100,000 person-years, and the point prevalence in 2015 was 31.7/100,000 inhabitants. The mean time from diagnosis to death was 21.9 years. The risk for any malignancy was three-fold and the risk for colorectal carcinoma was five-fold when comparing with the general population. During the first year after diagnosis of PSC, the risk for cholangiocarcinoma is 900-fold compared to the general population and after that 150-fold. SMR for all malignant neoplasms was 5.9 (95% CI 4.2–8.1).Conclusion: We found that the incidence of PSC in the HUS area in Finland is similar or higher than previously reported from other countries. The prevalence is markedly higher than reported elsewhere, probably due to the active search of the disease, suggesting that the disease is underdiagnosed.

No evidence for increased prevalence of colorectal carcinoma in 399 Dutch patients with Birt-Hogg-Dub\xe9 syndrome

BackgroundPreviously, it has been suggested that colorectal polyps and carcinomas might be associated with Birt-Hogg-Dubé syndrome. We aimed to compare the occurrence of colorectal neoplasms between Dutch patients with Birt-Hogg-Dubé syndrome and their relatives without Birt-Hogg-Dubé syndrome.MethodsIn all, 399 patients with a pathogenic FLCN mutation and 382 relatives without the familial FLCN mutation were included. Anonymous data on colon and rectum pathology was provided by PALGA: the Dutch Pathology Registry.ResultsNo significant difference in the percentage of individuals with a history of colorectal carcinoma was found between the two groups (3.6% vs 2.6%, p = 0.54). There was also no significant difference between the age at diagnosis, diameter, differentiation and location of the colorectal carcinomas. Significantly more individuals with Birt-Hogg-Dubé syndrome underwent removal of colorectal polyps (12.2% vs 6.3%, p = 0.005). However, there was no significant difference between the number of polyps per person, the histology, grade of dysplasia and location of the polyps.ConclusionOur data do not provide evidence for an increased risk for colorectal carcinoma in Birt-Hogg-Dubé syndrome, arguing against the need for colorectal surveillance. The difference in polyps might be due to a bias caused by a higher number of colonoscopies in patients with Birt-Hogg-Dubé syndrome.

Prophylactic Risk-reducing Hysterectomies and Bilateral Salpingo-oophorectomies in Patients With Lynch Syndrome: A Clinicopathologic Study of 29 Cases and Review of the Literature.

Lynch syndrome (LS) is associated with an increased risk for colorectal, endometrial, and ovarian carcinomas in women. Risk-reducing hysterectomy and bilateral salpingo-oophorectomy (RRHSO) has been shown to be a cost-effective form of management and prevention of gynecological malignancies in patients with LS. Studies of incidental gynecologic malignancies identified in RRHSO are limited. In addition, recommendations on optimal handling of this type of specimen have ranged from submitting for microscopic examination the entire endometrium, fallopian tubes and ovaries to submitting only routine representative sections of these organs. In this study, we present the clinicopathologic findings of 29 cases of LS patients that underwent risk-reducing gynecologic surgery at our institution over a period of 13 yr. Clinical-pathologic information was obtained from the patients' charts and pathology reports. Significant pathologic abnormalities were identified in 17% (5/29) of cases, all showing endometrial hyperplasia. Four of them with atypical and 1 without atypical. All of our cases with endometrial pathology had significant findings on preoperative endometrial sampling. To further study the recommendation of in toto submission of the endometrium, ovaries and fallopian tubes and the utility of preoperative endometrial sampling, we undertook a literature review of all the reported cases of incidental pathologic findings identified in RRHSO. The findings of our cohort and the literature reviewed support in toto submission of endometrium, and adnexal structures in the absence of gross lesions. In addition, our findings show a definite benefit for preoperative endometrial sampling as part of the workup for LS patients undergoing RRHSO.

KRAS SNPs are related to colorectal cancer susceptibility and survival in Chinese people.

Aim:KRAS SNPs may increase KRAS transcription and KRAS levels. SNPs of KRAS 3'UTR can affect carcinoma risk and prognosis. Materials & methods: The rs8720 and rs7960917 in KRAS 3'UTR for colorectal carcinoma (CRC) risk and survival were investigated in a case-control study. Association between SNPs and CRC risk, survival analysis were analyzed by an unconditional logistic regression model, log-rank test, Kaplan-Meier estimation, Cox regression model and one-way analysis of variance. Results & conclusion: The genotype CT of rs8720 was significantly increased risk of CRC, decreased overall survival and event-free survival, and KRAS mRNA and protein expressions were significantly increased in individuals with rs8720 CT, TT genotype. rs8720 may be an important factor in CRC development and prognosis.

Insulin enhances and metformin reduces risk of colorectal carcinoma in type-2 diabetes.

Identifying colorectal cancer associated risks is important for conducting a program for the survey and prevention of colorectal cancer. To investigate the association between use of insulin or metformin with colorectal cancer (CRC) in type 2 diabetes (T2DM). Population-based cohort study. Through analysis of National Health Insurance (NHI) database between 1998 and 2010 in Taiwan, we identified 66 324 T2DM patients aged ≥ 20 years and selected subjects without diabetes by 1: 1 randomly matching with the study cohort based on age, sex and index date. We followed up the participants until 31 December 2011 or when they withdrew from the NHI program. Compared with non-diabetic subjects, the T2DM patients exhibited an increased risk of CRC [adjusted HR (aHR) = 1.56, 95% confidence interval (CI) = 1.39-1.75], after adjustment for age, sex, urbanization level, comorbidities and examinations of colonoscopy, sigmoidoscopy, or stool occult blood test. Among the T2DM patients, insulin usage increased the risk of CRC (aHR = 1.86, 95% CI = 1.58-0-2.19) after adjustment for age, sex, urbanization level, comorbidities, metformin usage and examinations; nevertheless, metformin decreased the risk of CRC (aHR = 0.65, 95% CI = 0.54-0.77) after adjustment for age, sex, urbanization level, comorbidities, insulin usage and examinations. Compared with the non-insulin cohort, the risk of CRC tended to increase with the incremental dosage of insulin exposure. Our population-based cohort study demonstrated an association between T2DM and CRC. Among the T2DM patients, insulin use was associated with an increased risk of CRC and metformin use was associated with a decreased risk of CRC. Inability to obtain information on several potential confounding factors, such as lifestyle and dietary habits, is the major limitation of the study.

3043 Not All Bumps Are Equal, Mucosal Schwann Cell Hamartoma a Rare Subtype

INTRODUCTION: Benign mesenchymal polyps are an interesting group of colonic polyps. There has been a surge in the number of these polyps identified since legislation modified Medicare and began reimbursement for screening colonoscopy in patients at an average risk for colorectal carcinoma. It is important to differentiate between the different types of mesenchymal polyps given that some have correlation with hereditary diseases. CASE DESCRIPTION/METHODS: 66 year old male patient with history of hypertension presents for routine colorectal cancer screening colonoscopy. He is asymptomatic and has no family history of cancer including colon cancer. During the colonoscopy a small 5 mm polyp was found in the rectosigmoid which was removed using cold forceps polypectomy. The pathology was read as a benign mesenchymal polyp. Further staining with S-100 and CD 68 was done which revealed that this polyp was in fact a Schwann cell hamartoma. DISCUSSION: There has been 10 reported cases of mucosal schwann cell hamartoma in literature. Using immunohistochemistry for S100 highlights tissue with neural differentiation expanding the lamina propria of the colonic biopsy and CD68 highlights muciphages. These polyps resemble spindle cell proliferation and other neuronal tumors and are usually limited to the mucosa of the colon with no submucosal extension. They are usually solitary and patients do not have symptoms though a couple of cases reported finding them in the process of workup for diarrhea. Gibson and Hornick supplied the necessary name in 2009 in an attempt to differentiate it from other Schwann cell proliferation which is seen in entities like neurofibroma and ganglioneuroma. The importance of this entity is its lack of association with hereditary cancer syndromes, specifically neurofibromatosis type 1 (NF1) and multiple endocrine neoplasia 2B (RET) which is seen with neurofibromas. Also ganglioneuromatous polyposis and diffuse ganglioneuromatosis are seen in Cowden syndrome, Juvenile polyposis syndrome, MEN2B and NF1 however solitiary ganglioneuroma are not associated with hereditary diseases. It is important to differentiate this entity from others to prevent unnecessary and aggressive testing and treatment. Pathologists should include this differential as part of S 100 positive spindle cell proliferative lesions and gastroenterologists should be aware of the benign nature of this pathology.

Association of colorectal carcinoma and metabolic syndrome.

Aim Colorectal carcinoma is one of the most common neoplasms, especially in Western countries and those with westernisation. On the other hand, high rate of metabolic syndrome (MetSy) has also been noticed, as well as in Western countries. It seems like these two conditions are somehow connected. In this study, we wish to explore some characteristics of colorectal carcinoma and its correlation with MetSy. Methods In this retrospective study the data were taken from medical records of 67 patients with colorectal carcinoma, and for 30 healthy controls. Input parameters of patients were compared mutually, as well as with parameters of healthy, control examinees that had negative screening colonoscopy for neoplasm. Results Average age of patients was 68 years. The most frequent localisation of neoplasm was on rectum (53.7%) and most frequent level was Dukes C (38.8%). The patients had MetSy more frequently when compared with controls (p=0.048), and also they had more MetSy components (p=0.006). The link between MetSy and localisation of neoplasm was not found, neither with its pathohystological characteristics. Conclusion Patients with MetSy should be warned about the increased risk of colorectal carcinoma, and, in this way, motivated for earlier and more frequent screening colonoscopies, as well as of a change of unhealthy lifestyle.

Long-term status of predicted body fat percentage, body mass index and other anthropometric factors with risk of colorectal carcinoma: Two large prospective cohort studies in the US.

Anthropometric measurements, such as body mass index (BMI), waist circumference, and body fat percentage, have been used as indicators of obesity. Despite evidence that excess body fat is a risk factor for colorectal carcinoma (CRC), the magnitude of the association of BMI and other obesity indicators with the long-term risk of CRC remains unclear. Utilizing a Cox proportional hazards regression model, we examined differential associations between predicted body fat percentage and BMI with the risk of CRC (n = 2,017). The associations between CRC incidence and different adiposity measurements were also assessed. Predicted body fat percentage had a similar increased risk of CRC risk as BMI. In multivariable-adjusted analyses, the hazard ratio for CRC in the second to fifth quintiles (compared to the first quintile) of predicted body fat percentage were 1.32, 1.31, 1.53 and 2.09 for men (ptrend < 0.001) and 0.91, 0.90, 0.98 and 1.15 for women (ptrend = 0.03). Among various anthropometric measurements, predicted fat mass and waist circumference were slightly more strongly associated with CRC risk than BMI. In conclusion, the novel anthropometric prediction equations provided further evidence that a greater amount of body fat might contribute to CRC risk in both sexes. An innovative approach enabled us to estimate the susceptibilities of specific body composition with CRC risk, in an inexpensive and minimally invasive manner. Furthermore, the typically used measures of BMI and waist circumference are robust measures of adiposity to predict cancer risk in a relatively healthy population.

Helicobacter pylori infection and the risk of colorectal carcinoma: a systematic review and meta-analysis.

Helicobacter pylori is a gram-negative bacterium that is colonized in the stomach. H. pylori infection can lead to a series of stomach diseases. However, the relationship between H. pylori infection and colorectal cancer is currently controversial. Therefore, we performed this meta-analysis to further understand the relationship between H. pylori infection and colorectal cancer. We conducted a comprehensive retrieval from electronic databases, included the PubMed, Medline, China National Knowledge Infrastructure (CNKI), and China Wanfang Data Knowledge Service Platform databases (Wanfang Databases) through May 1st, 2018. We used the search terms H. pylori and colorectal cancer or colorectal carcinoma and collected all relevant studies to explore the association between H. pylori infection and colorectal cancer. Twenty-seven studies including 14357 cases were included. H. pylori infection was associated with an increased risk of colorectal cancer. A pooled odds ratio (OR) of 1.27 with a 95% CI of 1.17-1.37 (P<0.001) was calculated by using a fixed-effects model (I2=45.5%, P=0.006). The subgroup analysis revealed that H. pylori infection was associated with an increased risk of colorectal cancer in the subgroups of Western countries (OR=1.34, 95% CI: 1.14-1.57) (P<0.001), serological testing (OR=1.20, 95% CI: 1.08-1.34) (P=0.001), multiple methods of testing (OR=2.63, 95% CI: 1.09-6.31) (P=0.031), cross-sectional studies (OR=1.92, 95% CI: 1.17-3.16) (P=0.010) and case-control studies (OR 1.26, 95% CI: 1.16-1.36) (P<0.001). The present meta-analysis provides evidence suggests that a positive association between H. pylori infection and the risk of colorectal cancer.

Diet, obesity and colorectal carcinoma risk: results from a national cancer registry-based middle-eastern study

BackgroundCancer of colon and rectum (colorectal) is one of the most common cancers worldwide. There is a scarcity of published data on the risk factors for colorectal cancer (CRC) from the Middle-Eastern countries specifically in Kuwait. Therefore, this matched case-control study sought to examine the risk factors associated with CRC in Kuwait.MethodsOne hundred and three histopathologically confirmed colorectal cancer cases were recruited from Kuwait Cancer Control Centre Registry. Two hundred and six controls matched with cases (2:1 ratio) on age, gender and nationality were selected from medical, ophthalmology, orthopedic and/ or surgical out-patient clinics at three main general hospitals in Kuwait. A structured questionnaire was used to collect the data from cases and controls through face-to-face interview. Adjusted matched odds ratios (mORadj) and their 95% confidence intervals (CI) were estimated using a multivariable conditional logistic regression model.ResultsMultivariable conditional logistic regression model showed that cases were 4.3 times more likely to have had attainted obesity (BMI ≥ 30) in their lifetime compared to controls (mORadj = 4.3; 95% CI: 1.6–11.4). Compared to controls, cases rarely consumed fruits and vegetable (mORadj = 20.8; 95% CI: 4.4–99.5), tended to consume red meat 2–3 times a week (mORadj = 3.8; 95% CI: 1.6–8.7) or more than 4 times a week (mORadj = 9.4; 95% CI: 2.5–35.4). Reportedly cases compared to controls frequently (nearly every week) suffered from constipation (mORadj = 5.6; 95% CI: 1.9–16.5). However, CRC cases were less likely than controls to have been diagnosed in the past with hypercholesterolemia (mORadj = 0.3; 95% CI: 0.2–0.7) or diabetes mellitus type II (mORadj = 0.4; 95% CI: 0.2–0.8).ConclusionsObesity, excessive red meat consumption and infrequent fruits/vegetables intake were associated with an increased CRC risk. Overcoming identified pitfalls in dietary pattern and maintenance of healthy weight may help minimize CRC risk in Kuwait and perhaps other countries in the region. Further studies on genetic basis in conjunction with life styles and dietary factors may unravel their joint contributions to CRC risk and furnish tools for curtailing CRC risk in this and other similar populations.

Smoking and Risk of Colorectal Cancer Sub-Classified by Tumor-Infiltrating T Cells.

Evidence indicates not only carcinogenic effect of cigarette smoking but also its immunosuppressive effect. We hypothesized that the association of smoking with colorectal cancer risk might be stronger for tumors with lower anti-tumor adaptive immune response. During follow-up of 134 981 participants (3 490 851 person-years) in the Nurses' Health Study and Health Professionals Follow-up Study, we documented 729 rectal and colon cancer cases with available data on T-cell densities in tumor microenvironment. Using the duplication-method Cox regression model, we examined a differential association of smoking status with risk of colorectal carcinoma subclassified by densities of CD3+ cells, CD8+ cells, CD45RO (PTPRC)+ cells, or FOXP3+ cells. All statistical tests were two-sided. The association of smoking status with colorectal cancer risk differed by CD3+ cell density (Pheterogeneity = .007). Compared with never smokers, multivariable-adjusted hazard ratios for CD3+ cell-low colorectal cancer were 1.38 (95% confidence interval = 1.09 to 1.75) in former smokers and 1.59 (95% confidence interval = 1.14 to 2.23) in current smokers (Ptrend = .002, across smoking status categories). In contrast, smoking status was not associated with CD3+ cell-high cancer risk (Ptrend = .52). This differential association appeared consistent in strata of microsatellite instability, CpG island methylator phenotype, or BRAF mutation status. There was no statistically significant differential association according to densities of CD8+ cells, CD45RO+ cells, or FOXP3+ cells (Pheterogeneity > .04, with adjusted α of 0.01). Colorectal cancer risk increased by smoking was stronger for tumors with lower T-lymphocyte response, suggesting an interplay of smoking and immunity in colorectal carcinogenesis.

Loss of solute carrier family 7 member 2 exacerbates inflammation-associated colon tumorigenesis

Solute carrier family 7 member 2 (SLC7A2, also known as CAT2) is an inducible transporter of the semi-essential amino acid L-arginine (L-Arg), which has been implicated in wound repair. We have reported that both SLC7A2 expression and L-Arg availability are decreased in colonic tissues from inflammatory bowel disease patients and that mice lacking Slc7a2 exhibit a more severe disease course when exposed to dextran sulfate sodium (DSS) compared to wild-type (WT) mice. Here, we present evidence that SLC7A2 plays a role in modulating colon tumorigenesis in the azoxymethane(AOM)-DSS model of colitis-associated carcinogenesis (CAC). SLC7A2 was localized predominantly to colonic epithelial cells in WT mice. Utilizing the AOM-DSS model, Slc7a2–/– mice had significantly increased tumor number, burden, and risk of high-grade dysplasia versus WT mice. Tumors from Slc7a2–/– mice exhibited significantly increased levels of the proinflammatory cytokines/chemokines IL-1β, CXCL1, CXCL5, IL-3, CXCL2, CCL3, and CCL4, but decreased levels of IL-4, CXCL9, and CXCL10 compared to tumors from WT mice. This was accompanied by a shift toward pro-tumorigenic M2 macrophage activation in Slc7a2-deficient mice, as marked by increased colonic CD11b+F4/80+ARG1+ cells with no alteration in CD11b+F4/80+NOS2+ cells by flow cytometry and immunofluorescence microscopy. The shift toward M2 macrophage activation was confirmed in bone marrow-derived macrophages from Slc7a2–/– mice. In bone marrow chimeras between Slc7a2–/– and WT mice, the recipient genotype drove the CAC phenotype, suggesting the importance of epithelial SLC7A2 in abrogating neoplastic risk. These data reveal that SLC7A2 has a significant role in the protection from CAC in the setting of chronic colitis, and suggest that the decreased SLC7A2 in inflammatory bowel disease (IBD) may contribute to CAC risk. Strategies to enhance L-Arg availability by supplementing L-Arg and/or increasing L-Arg uptake could represent a therapeutic approach in IBD to reduce the substantial long-term risk of colorectal carcinoma.

Association between metabolic syndrome and colorectal carcinoma based on a case-control study

Objective To evaluate the association between metabolic syndrome and colorectal carcinoma. Methods A total of 900 patients with colorectal carcinoma from 2013 to 2016 in Qianfoshan Hospital Affiliated to Shandong University were selected as the case group and 1 774 non-colorectal carcinoma participants from health management center as the control group. Logistic regression model was used to identify the relationship between metabolic syndrome and colorectal carcinoma. Results Compared with the controls (27.0%), metabolic syndrome was more prevalent among cases (35.4%). The difference was statistically significant (χ2=20.33, P<0.01). Multivariate logistic regression analyses showed that metabolic syndrome as an entity increased colorectal carcinoma risk (OR=1.38, 95%CI: 1.08-1.75, χ2=17.68, P<0.01). Subjects with 2 and 3 or more components of the metabolic syndrome had an increased risk of colorectal carcinoma, and the ORs of colorectal carcinoma were 1.37 and 1.60, respectively. Gender-specific patterns were also observed in the association between metabolic syndrome, component and colorectal carcinoma (χ2=5.40, P=0.02; χ2=8.66, P<0.01). Conclusion Metabolic syndrome is associated with the occurrence of colorectal carcinoma. An increasing trend in risk of colorectal carcinoma with the number of metabolic syndrome components is observed. Key words: Metabolic syndrome X; Colorectal neoplasms; Case-control studies

Development of rectal cancer in a young patient with a retained rectum after total colectomy for Familial Adenomatous Polyposis

Familial Adenomatous polyposis (FAP) is an inherited disorder and it represents the most common gastro intestinal Polyposis syndrome. The mutation of germ line in the APC gene is the main cause for FAP. The FAP is an inherited syndrome characterized by multiple (more than hundred) polyps in the colorectum with high risk of colorectal carcinoma and existence of extra colonic manifestations. Cancer prevention and maintaining a good quality of life are the main goals of management. The recommended surgical modalities are total proctocolectomy and ileoanal pouch or ileorectal anastomosis for AFAP.

Efficacy and Follow-up of Segmental or Subtotal Colectomy in Patients With Colitis-Associated Neoplasia

The historical approach to neoplasia in the setting of chronic colitis was to perform a total proctocolectomy. Recent consensus and society guidelines1-3 suggest that when dysplastic lesions can be removed endoscopically, continued surveillance is appropriate. This is based on improvements in optical technologies and the low risk of metachronous colorectal carcinoma in these patients.4-6 We hypothesized that if a lesion was completely removed surgically and followed up endoscopically, metachronous colorectal carcinoma would be a rare occurrence. Thus, segmental resection may be offered as a definitive surgery in patients with chronic colitis and localized colorectal neoplasia in whom endoscopic resection is not feasible. Retention of the distal colon/rectum is expected to result in an overall improved quality of life compared with permanent ileostomy or an ileoanal J-pouch. Here, we report our experience and follow-up evaluation of segmental resections for preoperative neoplasia in patients with Crohn's disease (CD) or ulcerative colitis (UC).