Inflammatory bowel disease increases the risk of hepatobiliary pancreatic cancer: A two-sample Mendelian randomization analysis of European and East Asian populations.

BACKGROUND: Both inflammatory bowel disease (IBD) and hepato-pancreato-biliary cancers (HPBC) have been established to cause a huge socioeconomic burden. Epidemiological studies have revealed a close association between IBD and HPBC. METHODS: Herein, we utilized inverse-variance weighting to conduct a two-sample Mendelian randomization analysis. We sought to investigate the link between various subtypes of IBD and HPBC. To ensure the accuracy and consistency of our findings, we conducted heterogeneity tests, gene pleiotropy tests, and sensitivity analyses. RESULTS: Compared to the general population, IBD patients in Europe exhibited a 1.22-fold increased incidence of pancreatic cancer (PC) with a 95% confidence interval (CI) of 1.0022-1.4888 (p = 0.0475). We also found a 1.14-fold increased incidence of PC in Crohn's disease (CD) patients with (95% CI: 1.0017-1.3073, p = 0.0472). In the East Asian population, the incidence of hepatocellular carcinoma (HCC) was 1.28-fold higher (95% CI = 1.0709-1.5244, p = 0.0065) in IBD patients than in the general population. Additionally, ulcerative colitis (UC) patients displayed 1.12-fold (95% CI: 1.1466-1.3334, p < 0.0001) and 1.31-fold (95% CI: 1.0983-1.5641, p = 0.0027) increased incidences of HCC and cholangiocarcinoma (CCA), respectively. Finally, the incidence of PC was 1.19-fold higher in CD patients than in the general population (95% CI = 1.0741-1.3132, p = 0.0008). CONCLUSION: Our study validated that IBD is a risk factor for HPBC. This causal relationship exhibited significant heterogeneity in different European and East Asian populations.

Ethnic Differences in the Smoking-related Risk of Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: The association between smoking and inflammatory bowel disease [IBD] relies on old meta-analyses including exclusively non-Jewish White populations. Uncertainty persists regarding the role of smoking in other ethnicities. METHODS: We systematically searched Medline/PubMed, Embase, and Scopus for studies examining tobacco smoking and the risk of developing IBD, ie, Crohn's disease [CD] or ulcerative colitis [UC]. Two authors independently extracted study data and assessed each study's risk of bias. We examined heterogeneity and small-study effect, and calculated summary estimates using random-effects models. Stratified analyses and meta-regression were employed to study the association between study-level characteristics and effect estimates. The strength of epidemiological evidence was assessed through prespecified criteria. RESULTS: We synthesised 57 studies examining the smoking-related risk of developing CD and UC. Non-Jewish White smokers were at increased risk of CD (29 studies; relative risk [RR]: 1.95, 95% confidence interval [CI]: 1.69‒2.24; moderate evidence). No association was observed in Asian, Jewish. and Latin-American populations [11 studies; RR: 0.97; 95% CI: 0.83-1.13], with no evidence of heterogeneity across these ethnicities. Smokers were at reduced risk of UC [51 studies; RR: 0.55, 95% CI: 0.48-0.64; weak evidence] irrespectively of ethnicity; however, cohort studies, large studies, and those recently published showed attenuated associations. CONCLUSIONS: This meta-analysis did not identify any increased risk of CD in smokers in ethnicities other than non-Jewish Whites, and confirmed the protective effect of smoking on UC occurrence. Future research should characterise the genetic background of CD patients across different ethnicities to improve our understanding of the role of smoking in CD pathogenesis.

Inflammatory polyps occur more frequently in inflammatory bowel disease than other colitis patients.

BACKGROUND: Colitis is generally considered a risk factor for colon neoplasia. However, not all types of colitis seem to have equal neoplastic transformation potential. AIM: To determine the prevalence of colorectal polyps in a predominantly African American population with inflammatory bowel disease (IBD) and Non-IBD/Non-Infectious Colitis (NIC). METHODS: We retrospectively evaluated medical records of 1060 patients previously identified with colitis at Howard University Hospital, based on ICD-10 code. Among these, 485 patients were included in the study: 70 IBD and 415 NIC based on a thorough review of colonoscopy, pathology and clinical reports. Logistic regression analysis was applied to estimate the risk of polyps in patients with IBD compared to those with NIC after adjusting for age and sex. A subgroup analysis within the IBD group was performed. RESULTS: Of the 485 patients, 415 were NIC and 70 were IBD. Seventy-three percent of the NIC patients and 81% of the IBD patients were African Americans. Forty six percent of IBD and 41% of NIC cases were male. IBD patients were younger than NIC patients (median age of 38 years vs. 50, P < 0.001). The prevalence of all types of polyps was 15.7 and 8.2% in the IBD and NIC groups, respectively (P = 0.045). Among patients with polyps, the prevalence of inflammatory polyps was higher in the IBD group (55%) compared to the NIC group (12%). After adjusting for age, sex and race, odds ratio of inflammatory polyps in IBD patients was 6.0 (P = 0.016). Adenoma prevalence was 4.3% (3/70) in IBD patients and 3.9% (16/415) in the NIC patients (p = 0.75). The anatomic distribution of lesions and colitis shows that polyps occur predominantly in the colitis field regardless of colitis type. More polyps were present in the ulcerative colitis patients when compared to Crohn's disease patients (27% vs. 5%, P < 0.001) within the IBD group. CONCLUSION: Our study shows that inflammatory polyps are more common in IBD patients when compared to NIC patients. Most polyps were in the same location as the colitis.

Comparison of Disease Phenotypes and Clinical Characteristics Among South Asian and White Patients with Inflammatory Bowel Disease at a Tertiary Referral Center.

BACKGROUND: The prevalence and clinical features of inflammatory bowel disease (IBD) vary among different racial and ethnic groups. The aim of this study was to compare the clinical and phenotypic features of Crohn's disease (CD) and ulcerative colitis (UC) in South Asian patients living in the United States with those of a white cohort. METHODS: The demographic, clinical, and phenotypic characteristics of 73 South Asian patients (31 CD and 42 UC) who presented initially to our tertiary referral center from 2012 to 2016 and had subsequent follow-up were retrospectively compared with those of 408 consecutive white patients (245 CD and 163 UC). RESULTS: South Asian IBD patients were significantly more likely to have UC (58.0% vs 40.0%; P = 0.005) than white patients. South Asians with CD were less likely to have a family history of IBD (9.7% vs 26.9%; P = 0.037) and required fewer CD-related surgeries (22.5% vs 46.1; P = 0.012). South Asians were also less likely to be active or former smokers in both the CD (P = 0.004) and UC (P = 0.020) groups. South Asians with UC had a higher incidence of Clostridium difficile infection compared with white patients (19.0% vs 8.6%; P = 0.050). CONCLUSIONS: A cohort of South Asian patients with IBD were more likely to have UC and had differing family and tobacco risk factors, requirements for surgery, and Clostridium difficile infection rates as compared with white patients.

Characteristics of inflammatory bowel disease in patients of Roma/Gypsy ethnicity. A case-control study.

BACKGROUND: Peculiarities of inflammatory bowel disease (IBD) have been explored in ethnic groups, such as Asians, Hispanics, and Afro-Americans, but not in other ethnic minorities, such as Roma/Gypsies. METHODS: In a retrospective, hospital-based study, all adult Roma/Gypsy patients included in the IBD databases of seven Spanish centres were identified as cases. For each Roma/Gypsy patient, a Caucasian patient, matched for several demographic features, was searched as a control. Data on phenotypic features, therapeutic requirements, and familial aggregation were recorded. RESULTS: Sixty-eight Roma/Gypsy patients were identified, 29 of them being women. The mean age at diagnosis of IBD was 24.9±9.5years, and the mean time elapsed since diagnosis was 96.6±72.2months. Roma/Gypsy IBD patients showed a significantly higher rate of familial aggregation (43%) than their Caucasian controls (9%) (p=0.00001). CD in Roma/Gypsies had more often a complicated pattern (mainly penetrating) while UC patients showed a marked trend to more often developing extraintestinal manifestations. In addition, Roma/Gypsy IBD patients had a somewhat greater need for immunosuppressants, biological agents or surgery. CONCLUSIONS: These are the first data on IBD in Roma/Gypsy patients. Familial aggregation is the most prominent feature in these patients, suggesting a predominant role of genetics in its pathogenesis.

Racial disparities in surgical outcomes of patients with Inflammatory Bowel Disease.

BACKGROUND: Inflammatory Bowel Disease (IBD) has not historically been a focus of racial health disparities research. IBD has been increasing in the black community. We hypothesized that outcomes following surgery would be worse for black patients. METHODS: A retrospective cohort study of death and serious morbidity (DSM) of patients undergoing surgery for IBD was performed using data from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP 2011-2014). Multivariable logistic regression modeling was performed to evaluate associations between race and outcomes. RESULTS: Among 14,679 IBD patients, the overall rate of DSM was 20.3% (white: 19.3%, black 27.0%, other 23.8%, p < 0.001). After adjustment, black patients remained at increased risk of DSM compared white patients (OR: 1.37; 95% CI 1.14-1.64). CONCLUSIONS: Black patients are at increased risk of post-operative DSM following surgery for IBD. The elevated rates of DSM are not explained by traditional risk factors like obesity, ASA class, emergent surgery, or stoma creation.

Immunochip Meta-Analysis of Inflammatory Bowel Disease Identifies Three Novel Loci and Four Novel Associations in Previously Reported Loci.

BACKGROUND AND AIMS: Recent meta-analysis of genome-wide association studies have identified over 241 inflammatory bowel disease susceptibility loci. However, the known variants only account for a fraction of inflammatory bowel disease heritability. To identify additional susceptibility loci, we performed a trans-ethnic meta-analysis as well as an Asian-specific meta-analysis, using all published Immunochip association results of inflammatory bowel disease. METHODS: An inverse-variance fixed-effects meta-analysis was carried out across Korean and East Asian Immunochip datasets of 4156 cases and 4904 controls [Asian ancestry]. A trans-ethnic meta-analysis of inflammatory bowel disease was performed together with the European datasets of 38 155 cases and 48 485 controls genotyped on the immunochip using a Bayesian approach, Meta-Analysis of Trans-ethnic Association studies [MANTRA]. RESULTS: We identified seven novel associations, including three novel susceptibility loci at MYO10-BASP1, PPP2R3C/KIAA0391/PSMA6/NFKB1A and LRRK1 as well as four novel secondary associations within previously known loci at NCF4, TSPAN32, CIITA and VANGL2. The new loci further implicate alterations in B cell biology in Crohn's disease pathogenesis. The effects of five loci were universal across European and Asian ancestries, whereas the NCF4 and CIITA loci showed significant heterogeneity between European and East Asian populations. In addition, 103 previously known IBD loci showed supporting evidence of association with nominal significance [p < 0.05] in Asians. CONCLUSIONS: Our findings of new loci not previously associated with IBD support the importance of studying inflammatory bowel disease genetics in diverse populations.

Minority Pediatric Patients with Inflammatory Bowel Disease Demonstrate an Increased Length of Stay.

BACKGROUND: Genetic and other biological factors may lead to differences in disease behavior among children with inflammatory bowel disease of different races, which may be further modified by disparities in care delivery. Using the Kids' Inpatient Database, we aimed to evaluate differences in the management of pediatric patients with inflammatory bowel disease by race, focusing on length of stay (LOS). METHODS: We performed a cross-sectional analysis using 2000 to 2012 data from the Kids' Inpatient Database, a nationally representative database. We identified pediatric patients (≤18 years of age) with discharge diagnoses of Crohn's disease (CD) or ulcerative colitis (UC). We used multivariable logistic regression to evaluate the relationship between race and LOS, controlling for age, payer status need for surgery, and year of admission. RESULTS: We identified 27,295 hospitalizations for children with inflammatory bowel disease (62% CD and 38% UC), Compared with white patients with CD, black (adjusted odds ratio 1.37; 95% confidence interval, 1.22-1.53; P < 0.001) and Hispanic patients (adjusted odds ratio: 1.37; 95% confidence interval: 1.19-1.59; P < 0.001) with CD demonstrated increased odds of a LOS greater than the 75th percentile. When compared with white patients with UC, Hispanic patients also demonstrated increased odds of a LOS greater than the 75th percentile (adjusted odds ratio: 1.20; 95% confidence interval, 1.02-1.42, P = 0.015). CONCLUSIONS: After controlling for age, year of admission, and clinical phenotypes, black and Hispanic patients with CD and Hispanic patients with UC had longer LOS than white patients. These may be due to differences in provider/hospital characteristics, socioeconomic differences, and/or differences in genetics and other biological factors (see Video Abstract, Supplemental Digital Content 1, http://links.lww.com/IBD/B656).

An Analysis of IL-10/IL-10R Genetic Factors Related to Risk of Colon Cancer and Inflammatory Bowel Disease in a Han Chinese Population.

BACKGROUND: Patients with chronic inflammatory bowel disease (IBD) are at high risk of developing colon cancer and represent a valuable patient cohort for studying the correlation between chronic inflammation and cancer formation. Cytokines play key roles in the regulation of systemic inflammation, local tissue damage, and immunomodulation involved in tumor development and progression. Therefore, functional polymorphisms in genes that encode cytokines and cytokine receptors represent potential candidate genes associated with carcinogenesis. The present study aimed to ascertain if any of the candidate single nucleotide polymorphisms (SNPs) in inflammation-related genes IL-10/IL-10R are associated with colon cancer or IBD in Han Chinese population. METHODS: A case-control study in a Chinese Han cohort was conducted and included 375 patients with colon cancer, 278 patients with IBD, and 382 age and gender matched healthy controls. Genotyping of four candidate SNPs (IL-10 rs1800896, rs1800872, rs3024505, and IL-10R rs9610) was performed and analysis was done using the MassARRAY system based on the MALDI-TOF MS platform. RESULTS: The C allele at rs1800872 may be a protective factor incolon cancer (OR = 0.770; 95% CI: 0.653 - 0.909; p = 0.002). A decreased risk of colon cancer in patients with rs1800872 AC genotype (OR = 0.794; 95% CI, 0.664 - 950; p = 0.011), CC genotype (OR = 0.589; 95% CI, 0.372 - 0.933; p = 0.022) or AC/CC genotype (OR = 792; 95% CI, 0.678 - 0.925; p = 0.003) was observed, compared with the common AA genotype. Conversely, carriers of the variant T allele of rs3024505 flanking the IL-10 gene were at increased risk of IBD (OR = 1.999; 95% CI: 1.174 - 3.401; p = 0.009). Compared with the common CC genotype, carrying heterozygous (OR = 1.762; 95% CI, 1.030 - 3.012; p = 0.036), or heterozygous and homozygous combined (OR = 1.874; 95% CI, 1.105 - 3.177; p = 0.018) at the IL-10 rs3024505, was associated with increased risk of IBD. Stratified analysis showed that a positive association was identified between the AC/CC genotype at IL-10 rs1800872 and tumor stage (p = 0.029). CONCLUSIONS: These data suggest that the variants in the IL-10 gene may change the risk of both colon cancer and IBD. The C allele at rs1800872 may be a protective factor in colon cancer and the T allele at rs3024505 may be a risk factor in IBD in a Han Chinese population.

Human Papilloma Virus Awareness Among Hispanic Females with Inflammatory Bowel Disease.

Women with inflammatory bowel disease (IBD) may be at increased risk of human papilloma virus (HPV) infection and HPV-related malignancies, as many are immunocompromised secondary to the use of immunosuppressant agents. Several studies have addressed the knowledge about cervical cancer risk factors in different populations, particularly HPV infection and its association with cervical malignancies; most of these studies show poor patient knowledge. The purpose of this study is to describe the knowledge of females with IBD about HPV infection and the HPV vaccine. We performed a cross-sectional study in 147 consecutive patients attending the clinics of the University of Puerto Rico Center for IBD from 2009 to 2010. An interviewer-administered questionnaire was used to collect information on demographics, lifestyles, and HPV-related knowledge of participants. Bivariate analysis using the chi-square statistics and Fisher's exact test was used to examine factors associated with HPV awareness. The mean age of participants was 36.6 years (SD = 13.91 years). Three fourth (77 %) of women had awareness of the existence of HPV, and 58 % did know about the existence of HPV vaccines. Among those who had heard about HPV, 79.6 % knew that HPV can cause cervical cancer, and 57.5 % knew that the virus is sexually transmitted. Among those who knew of the vaccine, 75.3 % learned about its existence through the media, while only 15.3 %, through their health-care provider. Only three women within recommended ages (2 %) had been vaccinated against HPV, although 50 % of participants indicated that they would definitely/probably vaccinate against HPV in the future. A significant trend was observed, where more educated women were more likely to have heard of HPV (p for trend = 0.0017). Women who were high school graduates/some college (OR = 6.63, 95 % CI = 1.71-25.66) and those with at least an associate degree (OR = 11.69, 95 % CI = 3.05-45.89) were more likely to be aware of the HPV vaccine than women without a high school degree. Our study documents poor knowledge of HPV and HPV vaccine in this population of IBD patients in Puerto Rico. Although vaccination coverage is low in this population, women are receptive to the possibility of vaccination in the future. Given that this population may be at an increased risk of HPV infection and related morbidities, education and vaccination programs should be promoted among them.

Racial Disparities in Readmissions for Patients with Inflammatory Bowel Disease (IBD) After Colorectal Surgery.

BACKGROUND: The incidence of inflammatory bowel disease (IBD) in minorities is increasing, and health outcome disparities are becoming more apparent. Our aim was to investigate the contribution of race to readmissions in IBD patients undergoing colorectal surgery. DESIGN: The National Surgical Quality Improvement Program database from 2012 to 2013 was queried for all patients with IBD undergoing elective colorectal surgery. After stratifying by race, unadjusted univariate and bivariate comparisons were made. Primary outcome was all-cause 30-day readmission. Predictors of readmission were identified using multivariable logistic regression. RESULTS: Of the 2523 patients with IBD who underwent elective colon surgery, 15.0 % were readmitted within 30 days of index operation. Black patients constituted 7.7 % of the entire cohort. Black patients were significantly different in smoking status (27 vs. 22 %) and Crohn's diagnosis (84 vs. 73 %) (p < 0.05). Black patients had significantly higher readmission rates (20 vs. 15 %) and longer length-of-stays (8 vs. 6 days) after surgery (p < 0.05). On multivariable analysis, black race remained a significant predictor for 30-day readmissions in patients with IBD (odds ratio 1.6, 95 % confidence interval 1.1-2.5). CONCLUSIONS: Black patients with IBD have an increased risk for readmission after colorectal surgery. Efforts to reduce readmissions need to target not only well-studied risk factors such as postoperative complications, but also investigate non-NSQIP-measured elements such as social and behavioral determinants of health.

Association of STAT4 rs7574865 polymorphism with susceptibility to inflammatory bowel disease: A systematic review and meta-analysis.

OBJECTIVE: Association of Signal transducers and activators of transcription-4 (STAT4) gene polymorphism with susceptibility to inflammatory bowel disease have been investigated in a number of epidemiological studies, but the results are inclusive. The aim of this meta-analysis was to more precisely estimate the relationship. METHODS: The databases of Pubmed and CBM updated to October, 2014 were retrieved. Random- or fixed-effect model was used to estimate odd radio (OR) and corresponding 95% confidence interval (95%CI) on the basis of heterogeneity. RESULTS: Seven articles containing 2196 Crohn's disease (CD) cases, 1588 ulcerative colitis (UC) cases and 4126 controls were identified. We detected a significant association between STAT4 rs7574865 polymorphism and IBD susceptibility in overall population (GG vs. GT+TT, OR=0.855, 95% CI=0.760-0.962, P=0.009), but not in Caucasian and Asian population, respectively. No association was detected between rs7574865 polymorphism and CD susceptibility in overall, Asian and Caucasian population, respectively. Interestingly, a significant association was detected between rs7574865 with UC susceptibility in overall population (G vs. T, OR=0.881, 95% CI=0.798-0.972, P=0.012; GG vs. GT+TT, OR=0.788, 95% CI=0.679-0.914, P=0.002; GG vs. TT, OR=0.683, 95% CI=0.498-0.937, P=0.018) and Caucasians (GG vs. GT+TT, OR=0.833, 95% CI=0.701-0.990, P=0.038; GG+GT vs. TT, OR=0.667, 95% CI=0.456-0.975, P=0.037; GG vs. TT, OR=0.636, 95% CI=0.433-0.934, P=0.021), respectively, and a possible association was found in Asian population (GG vs. GT+TT, OR=0.709, 95% CI=0.503-0.998, P=0.049). CONCLUSIONS: STAT4 rs7574865 gene is IBD risk factor, and this gene polymorphism is associated with UC susceptibility, especially in Caucasians. To confirm these findings, further studies with more sample size are required for a definitive conclusion.

Ashkenazi Jewish origin protects against formation of antibodies to infliximab and therapy failure.

Infliximab is an anti-tumor necrosis factor (TNF) used for treatment of inflammatory bowel disease (IBD) as well as rheumatoid arthritis, psoriasis, and other inflammatory conditions. Antibodies to infliximab (ATI) develop in approximately 45% of infliximab-treated IBD patients and are correlated with loss of clinical response. Scarce data exist as to factors which predict infliximab immunogenicity.To investigate factors that may predict formation of antibodies to infliximab (ATI) and infliximab therapy failure an observational study of consecutive IBD patients treated with infliximab between 2009 and 2013 was performed. Trough levels of ATI were measured. Patients were monitored for disease activity using clinical activity indexes and were classified according to ATI formation and clinical response. All clinical and demographic parameters were analyzed for association with the designated outcomes.One hundred fifty-nine patients were included and 1505 sera were tested. On multivariate analysis, Jewish Ashkenazi ethnicity was protective against both development of ATI (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.17-0.7, P = 0.005) and treatment failure (OR 0.29, 95% CI 0.13-0.66, P = 0.003). Concomitant immunomodulator therapy was also negatively associated with immunogenicity and infliximab therapy failure (OR 0.31, 95% CI 0.15-0.65, P = 0.002; OR 0.42 95% CI 0.18-0.99, p = 0.04, respectively), whereas episodic therapy was positively associated with both outcomes (OR 4.2 95% CI 1.07-16.1, p = 0.04, OR 4.45 95% CI 1.2-16.6, p = 0.026 respectively). All other variables, including IBD type, gender, weight, age, smoking status and disease duration, were not predictive of ATI formation or clinical failure. However, among Crohn's disease patients, a non-stricturing non-penetrating phenotype was protective against ATI formation (OR 0.4, 95% CI 0.14-0.96, p = 0.04). P = 0.04, respectively), whereas episodic/interrupted therapy was positively associated with both outcomes (OR 4.2, 95% CI 1.07-16.1, P = 0.04; OR 4.45, 95% CI 1.2-16.6, P = 0.026, respectively). All other variables, including IBD type, sex, weight, age, smoking status, and disease duration, were not predictive of ATI formation or clinical failure. However, among Crohn disease patients, a nonstricturing nonpenetrating phenotype was protective against ATI formation (OR 0.4, 95% CI 0.14-0.96, P = 0.04).Jewish Ashkenazi ethnicity is protective of ATI formation and infliximab therapy failure. These findings suggest a role for ethnicity, and implicitly for genetic predisposition, in modulating the risk of anti-TNF immunogenicity and treatment unresponsiveness.

Immunohistochemical expression of SP-NK-1R-EGFR pathway and VDR in colonic inflammation and neoplasia.

AIM: To determine the expression of neurokinin-1 receptor (NK-1R), phosphorylated epidermal growth factor receptor (pEGFR), cyclooxygenase-2 (Cox-2), and vitamin D receptor (VDR) in normal, inflammatory bowel disease (IBD), and colorectal neoplasia tissues from Puerto Ricans. METHODS: Tissues from patients with IBD, colitis-associated colorectal cancer (CAC), sporadic dysplasia, and sporadic colorectal cancer (CRC), as well as normal controls, were identified at several centers in Puerto Rico. Archival formalin-fixed, paraffin-embedded tissues were de-identified and processed by immunohistochemistry for NK-1R, pEGFR, Cox-2, and VDR. Pictures of representative areas of each tissues diagnosis were taken and scored by three observers using a 4-point scale that assessed intensity of staining. Tissues with CAC were further analyzed by photographing representative areas of IBD and the different grades of dysplasia, in addition to the areas of cancer, within each tissue. Differences in the average age between the five patient groups were assessed with one-way analysis of variance and Tukey-Kramer multiple comparisons test. The mean scores for normal tissues and tissues with IBD, dysplasia, CRC, and CAC were calculated and statistically compared using one-way analysis of variance and Dunnett's multiple comparisons test. Correlations between protein expression patterns were analyzed with the Pearson's product-moment correlation coefficient. Data are presented as mean ± SE. RESULTS: On average, patients with IBD were younger (34.60 ± 5.81) than normal (63.20 ± 6.13, P < 0.01), sporadic dysplasia (68.80 ± 4.42, P < 0.01), sporadic cancer (74.80 ± 4.91, P < 0.001), and CAC (57.50 ± 5.11, P < 0.05) patients. NK-1R in cancer tissue (sporadic CRC, 1.73 ± 0.34; CAC, 1.57 ± 0.53) and sporadic dysplasia (2.00 ± 0.45) were higher than in normal tissues (0.73 ± 0.19). pEGFR was significantly increased in sporadic CRC (1.53 ± 0.43) and CAC (2.25 ± 0.47) when compared to normal tissue (0.07 ± 0.25, P < 0.05, P < 0.001, respectively). Cox-2 was significantly increased in sporadic colorectal cancer (2.20 ± 0.23 vs 0.80 ± 0.37 for normal tissues, P < 0.05). In comparison to normal (2.80 ± 0.13) and CAC (2.50 ± 0.33) tissues, VDR was significantly decreased in sporadic dysplasia (0.00 ± 0.00, P < 0.001 vs normal, P < 0.001 vs CAC) and sporadic CRC (0.47 ± 0.23, P < 0.001 vs normal, P < 0.001 vs CAC). VDR levels negatively correlated with NK-1R (r = -0.48) and pEGFR (r = -0.56) in normal, IBD, sporadic dysplasia and sporadic CRC tissue, but not in CAC. CONCLUSION: Immunohistochemical NK-1R and pEGFR positivity with VDR negativity can be used to identify areas of sporadic colorectal neoplasia. VDR immunoreactivity can distinguish CAC from sporadic cancer.

Manifestations of inflammatory bowel disease in patients of Haitian and Cape Verdean descent.

OBJECTIVE: Several studies have reported unique ethnic phenotypes of inflammatory bowel disease (IBD). An appreciation of disease manifestations in different populations may improve clinical outcomes. There are no studies examining IBD in patients of Haitian or Cape Verdean descent. We sought to define the IBD phenotype in these populations. MATERIALS AND METHODS: This was a retrospective review comparing Haitian and Cape Verdean immigrant IBD patients to Caucasians, all receiving care at Boston Medical Center in Boston, Massachusetts, USA. The following variables were analyzed: family history, smoking history, vaccinations/cancer screening, age of diagnosis, disease duration, disease location, medication use, and complications. RESULTS: Thirty-one Haitians and 21 Cape Verdeans were matched to Caucasian controls. Haitians (mean age 42 years) and Cape Verdeans (mean age 47 years) with Crohn's disease were diagnosed with IBD later than Caucasians (mean age 31 years, p = 0.04 and 0.02, respectively). Haitians with Crohn's were less likely to have a history of tobacco use compared to Caucasians (13% vs. 51%, p = 0.02). Cape Verdeans with Crohn's were less likely to have perianal involvement (0% vs. 50%, p = 0.01). Haitians with IBD were less likely to have ever used glucocorticoids (48% vs. 76%, p = 0.02). There was no difference in vaccination rates, cancer screening, or disease complications. CONCLUSIONS: This study demonstrates differences in IBD presentation and disease course among Haitians and Cape Verdeans. Our results suggest a more mild disease in these ethnic groups. Future studies are needed to identify the influence of environmental factors.

Inflammatory bowel disease among Bedouin Arabs in southern Israel: urbanization and increasing prevalence rates.

BACKGROUND AND AIM: Inflammatory bowel disease (IBD) has been associated with genetic and environmental factors, including urban living. IBD was rare in the Israeli Bedouin community 30 years ago. Over recent decades, a large proportion of this community has undergone a transition from a nomadic to a western lifestyle. Our aim was to carry out an updated evaluation of the clinical and epidemiological features of IBD in the Bedouin sector of southern Israel. METHODS: All Bedouin patients with a known diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) were included in the retrospective study. RESULTS: The cohort included 31 CD patients and 31 UC patients. The mean age of the patients at diagnosis was 29±10.9 and 35±17.5 years for CD and UC, respectively. The prevalence rate for CD was 15.5/100,000 and the incidence rate was 0.8-3.55/100,000. Fourteen of the CD patients (45%) had ileal disease and 64.5% had inflammatory disease behavior according to the Montreal classification. Eleven of the CD patients (35%) were treated with anti-TNF-α and 26% had undergone surgery. Over the previous decade, the prevalence of UC was 14/100,000 and the incidence was 0.5-2.39/100,000. Eighteen UC patients (58%) had left-sided colitis. Three (9.7%) had undergone total colectomy for severe disease. CONCLUSION: We found an increased prevalence of IBD in the Bedouin population, associated with their change in lifestyle over previous decades. However, the prevalence is still markedly lower than that in other population groups. A high percentage of patients were treated with anti-TNF-α and/or surgery.

Ubiquitous occurrence of birth-cohort patterns in inflammatory bowel disease.

BACKGROUND AND AIMS: The aim of the present study was to demonstrate the ubiquitous occurrence of the birth-cohort phenomenon of inflammatory bowel disease among US whites and nonwhites, as well as males and females. METHODS: Mortality from Crohn's disease and ulcerative colitis in the USA between 1950 and 2010 were analyzed to discern underlying birth-cohort patterns affecting both their time trends. Age-standardized cohort mortality ratio was used as a summary statistic to represent the overall mortality associated with consecutive birth-cohorts. RESULTS: The cohort-age contours of Crohn's disease aligned to form one hyperbola with an initial rise between 1865 and 1935 and a subsequent decline. This pattern was confirmed by the time trends of the corresponding standardized cohort mortality ratio values. In ulcerative colitis, the individual cohort-age contours also aligned into one hyperbola that appeared shifted towards earlier generations by about 30 years when compared with Crohn's disease. Similar trends were observed in men and women or whites and nonwhites analyzed separately. CONCLUSION: The birth-cohort patterns indicate that exposure to two separate risk factors must have occurred in both diseases during an early period of life. In the USA, these exposures have changed over historical times similarly in both sexes and different ethnic groups.