UC Cases Research Articles

1160 SMOKING AND RISK OF UROTHELIAL CELL CARCINOMA OF THE BLADDER: RESULTS FROM A CONTEMPORARY, PROSPECTIVE COHORT STUDY

You have accessJournal of UrologyBladder Cancer: Detection and Screening1 Apr 20101160 SMOKING AND RISK OF UROTHELIAL CELL CARCINOMA OF THE BLADDER: RESULTS FROM A CONTEMPORARY, PROSPECTIVE COHORT STUDY James Hotaling, Jonathan Wright, Michael Porter, and Emily White James HotalingJames Hotaling More articles by this author , Jonathan WrightJonathan Wright More articles by this author , Michael PorterMichael Porter More articles by this author , and Emily WhiteEmily White More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.660AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Cigarette smoking is one the leading causative factors associated with urothelial cell carcinoma of the bladder (UC). A number of case-control studies have investigated the relationship between both duration of current smoking and length of time from smoking cessation with UC. Fewer prospective cohort studies have been conducted on a contemporary population. Using a large prospective cohort, we explore the relationship between current and former smoking and risk of UC. METHODS Participants in the VITamins And Lifestyle Study (VITAL) comprised the study population, which included 77,719 Washington State residents aged 50-76 years. Baseline self-administered questionnaires were completed in 2000-2002 on health history and cancer risk factors. Participants with prevalent UC were excluded. Incident UC cases were determined via linkage to the Surveillance, Epidemiology, and End Results (SEER) cancer registry through 2007. Smoking history was categorized as ever use (never, former, current); pack years smoked (quartiles of use for current and former smokers); and time since quitting in years (for former smokers). Multivariate cox regression was used to estimate the Hazard ratios (HR) for developing UC by smoking status controlling for age, gender and race. RESULTS A total of 330 incident UC cases were identified. Of those without UC, 8% were current smokers and 44% were former smokers. The risk of UC was 2-fold higher (95% CI 1.5—2.6) for former smokers and 4-fold higher (95% CI 2.9—5.8) for current smokers compared to those who never smoked. Both pack years of smoking and years since quitting were associated with the risk of developing UC (both pTrend < 0.01). Among former smokers, the 2-fold increased risk remained for all subsets of pack-years and years since quitting except for those with < 7.5 pack years of smoking. CONCLUSIONS In a contemporary, large prospective cohort, we confirm the 2-4 fold increase risk of UC in smokers, with a dose dependent effect seen for pack years smoked. The increased risk of developing UC persisted for more than 20 years after quitting smoking. Former smokers with less than 7.5 pack-years of smoking had no increased risk of bladder cancer. Seattle, WA© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e449 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information James Hotaling More articles by this author Jonathan Wright More articles by this author Michael Porter More articles by this author Emily White More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Inflammatory bowel disease activity assessed by fecal calprotectin and lactoferrin: correlation with laboratory parameters, clinical, endoscopic and histological indexes

BackgroundResearch has shown that fecal biomarkers are useful to assess the activity of inflammatory bowel disease (IBD). The aim of the study is: to evaluate the efficacy of the fecal lactoferrin and calprotectin as indicators of inflammatory activity.FindingsA total of 78 patients presenting inflammatory bowel disease were evaluated. Blood tests, the Crohn's Disease Activity Index (CDAI), Mayo Disease Activity Index (MDAI), and Crohn's Disease Endoscopic Index of Severity (CDEIS) were used for the clinical and endoscopic evaluation. Two tests were performed on the fecal samples, to check the levels of calprotectin and lactoferrin. The performance of these fecal markers for detection of inflammation with reference to endoscopic and histological inflammatory activity was assessed and calculated sensitivity, specificity, accuracy.A total of 52 patient's samples whose histological evaluations showed inflammation, 49 were lactoferrin-positive, and 40 were calprotectin-positive (p = 0.000). Lactoferrin and calprotectin findings correlated with C-reactive protein in both the CD and UC groups (p = 0.006; p = 0.000), with CDAI values (p = 0.043; 0.010), CDEIS values in DC cases (p = 0,000; 0.000), and with MDAI values in UC cases (p = 0.000).ConclusionFecal lactoferrin and calprotectin are highly sensitive and specific markers for detecting intestinal inflammation. Levels of fecal calprotectin have a proportional correlation to the degree of inflammation of the intestinal mucosa.

Fecal calprotectin in differential diagnosis between irritable bowel syndrome and inflammatory bowel disease

AIM: To assess the value of fecal calprotectin as a non-invasive screening biomarker in differential diagnosis of irritable bowel syndrome (IBS) and inflammatory bowl disease (IBD) using ELISA quantitative analysis.METHODS: A total of 92 fresh fecal samples were collected from the patients, including 23 cases of UC, 4 cases of CD, 55 cases of irritable bowel syndrome (IBS) and 20 healthy volun-teers. EK-CAL was used to quantitatively dete rmine the level of fecal calprotection.RESULTS: The level of fecal calprotection was 77.15 ± 160.9 μg/g in healthy volunteers, 46.08 ± 131.97 μg/g in IBS patients, 851.34 ± 522.19 μg/g in IBD patients, respectively. There was no signifi cant difference between IBS patients and healthy volunteers (P 0.05) in levels of fecal calprotection, but there was remarkable difference between the patients with IBS and healthy volunteers. The sensitivity and specif icity of fecal calprotection in differentiating the IBD from IBS was 86.7%, 96.3%, respectively.CONCLUSION: Detection of fecal calprotectin is simple, inexpensive, repeatable and non-invasive. It can be used as a biomarker in differentiating irritable bowel syndrome from inflammatory bowel disease.

Downregulation of sodium transporters and NHERF proteins in IBD patients and mouse colitis models: Potential contributors to IBD-associated diarrhea

One of the most common symptoms among patients with inflammatory bowel disease (IBD) is diarrhea, which is thought to be contributed by changes in electrolyte transport associated with intestinal inflammation. This study was designed to test the hypothesis that intestinal Na(+)-related transporters/channels and their regulatory proteins may be downregulated as a potential contributor to IBD-associated diarrhea. SDS-PAGE and Western blotting and/or confocal immunomicroscopy were used to examine the expression of Na(+)/H(+)-exchangers 1-3 (NHE1-3), epithelial Na(+) channel (ENaC), Na(+)/K(+)-ATPase, the intracellular Cl(-) channel 5 (ClC-5), and NHE3 regulatory factors (NHERF1,2) in ileal and colonic pinch biopsies from IBD patients and noninflammatory controls, as well as from colonic mucosa of dextran sodium sulfate (DSS)- and TNBS-induced acute murine IBD models. NHE1,3 (but not NHE2), beta-ENaC, Na(+)/K(+)-ATPase-alpha, ClC-5, and NHERF1 were all downregulated in sigmoid mucosal biopsies from most cases of active UC and/or CD compared to controls. NHE3 was also decreased in ileal mucosal biopsies of active CD, as well as in approximately 50% of sigmoid biopsies from inactive UC or CD. Importantly, similar downregulation of NHE1,3, beta-ENaC, and NHERF1,2 was also observed in the mouse colon (but not ileum) of DSS- and TNBS-induced colitis. IBD-associated diarrhea may be due to a coordinated downregulation of multiple Na(+) transporter and related regulatory proteins, including NHE1,3, Na(+)/K(+)-ATPase, and ENaC, as well as NHERF1,2, and ClC-5, all of which are involved directly or indirectly in intestinal Na(+) absorption.

Utilization of Cervical Testing Among Women with Inflammatory Bowel Disease

Purpose: Women with inflammatory bowel disease (IBD) have a higher incidence of abnormal Pap smear compared to women without IBD. However, the actual rate of cervical testing among women with IBD is unknown. We aimed to determine cervical testing rates among a large sample of women with IBD and specifically among women with IBD on immunosuppressant medications. We also aimed to identify specific risk factors associated with poor cervical testing rates among women with IBD in order to target future quality improvement initiatives. Methods: We extracted medical and pharmacy claims from the PharMetrics Patient-Centric Database, containing data from 87 health plans in 33 states spanning the period January 2003-December 2005. We identified cases of CD and UC with claims for at least 3 IBD-associated visits or at least 1 visit and 1 IBD-specific prescription. For each case, we randomly selected up to 3 non-IBD controls, matched for age, health plan, and geographic region. Using logistic regression, we compared utilization of cervical testing (identified by a validated claims algorithm) by IBD case status, age, immunosuppressive medication use, Medicaid insurance status (a proxy for socioeconomic status) and whether a primary care physician (PCP) was seen. Results: Only 70.4% of women with IBD (N = 9356) and 65.2% of their non-IBD matched controls (N = 25849) received recommended cervical testing (at least once every three years). Women with IBD who had a primary care visit had improved odds of cervical testing (OR 1.37 95% CI 1.19–1.59). Factors associated with reduced cervical testing included Medicaid insurance (OR 0.28, 95% CI 0.19–0.41), immunosuppressant medication use (OR 0.81, 95% CI 0.74–0.88) and increasing age (OR 0.77; 95% CI 0.74–0.81 for each 10 year increase in age). When only women with IBD on immunosuppressive medications were evaluated (N = 7415), only 51.0% obtained cervical testing within a 15 month period (to approximate the recommended 12 month interval for immunosuppressed women). Those with a PCP had improved odds of cervical testing (OR 1.28, 95% CI 1.14–1.45). Those with Medicaid insurance had reduced odds of cervical testing (OR 0.54, 95% CI 0.39–0.74). Conclusion: Women with IBD, especially those with Medicaid insurance, have suboptimal cervical testing rates. Women with IBD who had at least 1 visit to a primary care physician had improved rates of recommended cervical testing. Quality improvement initiatives are needed in order to improve preventive services, including cervical testing, for women with IBD.

Differences in the incidence of flares or new onset of inflammatory bowel diseases in patients with ankylosing spondylitis exposed to therapy with anti–tumor necrosis factor α agents

Ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) are clinically and pathologically linked. Anti-tumor necrosis factor (anti-TNF) agents are efficacious in treating AS, but not all are equally effective in treating IBD (Crohn's disease [CD] and ulcerative colitis [UC]). The purpose our study was to analyze the incidence of flares and new onset of IBD in patients with AS treated with anti-TNF agents. Data from 9 trials, 7 placebo-controlled trials and 2 open studies, were analyzed. Data were available on 419 AS patients exposed to etanercept (625 patient-years), 366 exposed to infliximab (618 patient-years), 295 exposed to adalimumab (132 patient-years), and 434 placebo patients (150 patient-years). A history of IBD was reported in 76 of 1,130 patients (6.7%). There were 2 reports of IBD while receiving placebo (1.3 per 100 patient-years), 1 while receiving infliximab, and 3 while receiving adalimumab. Among the 14 IBD cases receiving etanercept (2.2 per 100 patient-years) there were 8 CD and 6 UC cases, significantly different from infliximab (P = 0.01) but not from placebo. Patients with a history of IBD had an IBD flare odds ratio of 18.0 (95% confidence interval [95% CI] 2-154) while taking etanercept and 4.2 (95% CI 0.4-44) while taking adalimumab, in comparison with infliximab. The incidence rates of new onset of IBD showed no significant difference between etanercept (0.8 per 100 patient-years) and placebo (0.5 per 100 patient-years). New onset and flare of IBD are infrequent events in AS patients receiving anti-TNF therapy. Infliximab (but not etanercept) largely prevents IBD activity. More data are required for adalimumab. The incidence of new onset of IBD was statistically not different from placebo for all anti-TNF agents.

Health Care Resource Utilization in Inflammatory Bowel Disease

The aim of this study was to quantify temporal changes in health care utilization by a population-based cohort of IBD. By using the University of Manitoba IBD Epidemiology Database we assessed utilization of outpatient and hospital services, estimating relative risk (RR) of utilization for IBD cases compared with a matched cohort of non-IBD controls and for CD versus UC. We tested differences in utilization between prevalence cohorts 1990-1991 and 2000-2001. Also, utilization of the 1987-1988 incidence cohort was followed forward 15 years from diagnosis. The probability, intensity, and volume of utilization were estimated. In 2000-2001, IBD patients compared with controls were more likely to have an outpatient visit (RR, 1.18; 95% confidence interval [CI], 1.17-1.19) and an overnight hospital stay (RR, 2.32; 95% CI, 2.16-2.49). CD cases were more likely than UC cases to be hospitalized (RR, 1.26; 95% CI, 1.11-1.43) and had a greater number of outpatient visits. From 1990-1991 to 2000-2001, IBD cases experienced a significant decrease in the likelihood of an outpatient surgical visit relative to non-IBD controls (P < .05), and for those cases who were hospitalized, CD cases tended to be less likely than UC cases to experience IBD-specific inpatient surgery (P < .07). Of the 1987-1988 incidence cohort, 80% of admissions that occurred during the follow-up period were during the first 5 years after diagnosis. In 2000-2001, health care utilization continued to be higher in IBD versus controls and CD versus UC; however, the gap in costly service utilization appeared to narrow between the latter pair.

Incidence of ulcerative colitis in Central Greece: A prospective study

To study the incidence of ulcerative colitis UC in the prefecture of Trikala, Central Greece. A prospective and population based epidemiological study of UC from 1990 to the end of 1994 was conducted. Trikala is a semirural prefecture of Central Greece with a population of 138 946 (census 1991). Three gastroenterologists (one hospital based, two private doctors) of the prefecture participated in this study. During the study period, 66 new histologically verified cases of UC were recorded. The mean annual incidence of the disease in 1990-1994 was 11.2 per 10(5) inhabitants (95%CI: 8.7-14.3). There was no difference between men and women (annual incidence: 10.5 and 12.0 per 10(5) inhabitants respectively), either among urban, semirural or rural populations (annual incidence: 11.7, 17.1 and 9.9 per 10(5) inhabitants respectively). The majority (56%) of the patients never smoked and a quarter were ex-smokers. About a half of all cases had proctitis. UC is common in Central Greece and its incidence is similar to that in North-Western European countries.

Immunohistochemical expression of cyclin D1, cyclin E, p21/waf1 and p27/kip1 in inflammatory bowel disease: correlation with other cell-cycle-related proteins (Rb, p53, ki-67 and PCNA) and clinicopathological features.

The expression patterns of cyclins D1 and E as well as cyclin-dependent kinase inhibitors p21/waf1 and p27/kip1 and their correlation with clinical parameters and other cell cycle regulators was investigated in inflammatory bowel disease (IBD). These molecular markers were localized immunohistochemically using the monoclonal antibodies anti-cyclin D1 (DCS-6), anti-cyclin E (13A3), anti-p21 (4D10) and anti-p27 (1B4) in 70 patients with IBD, 30 patients with colorectal cancer and eight healthy subjects. Data were analyzed statistically using the software program. Cyclin D1 expression was higher in both UC and CD compared with the healthy control group. In addition, CD cyclin D1 expression was higher compared with UC cases and colorectal carcinomas. Cyclin D1 expression was correlated with disease activity and cell proliferation in UC cases. A positive relationship of cyclin D1 with p27/kip1 in both UC and CD was detected. Cyclin E expression was higher in UC, CD and carcinomas compared with healthy control group and its expression correlated with proliferative activity in both UC and CD cases. p21/waf1 expression was higher in IBD cases compared with that of the control group, while a decreased p21/waf1 expression in the group of carcinomas was noted. This expression was correlated with disease activity in UC and the proliferative activity in both UC and CD. The expression of cyclins D1 and E as well as p21/waf1 was also correlated with the existence of dysplastic lesions. A lower p27/kip1 expression in the group of carcinomas compared with IBD cases and healthy controls was found. The expression patterns of cyclin D1, cyclin E, p21/waf1 and p27/kip1 in IBD may indicate their contribution in epithelial cell turnover and their possible implication in IBD-related dysplasia-carcinoma.

Presenting features of inflammatory bowel disease in Great Britain and Ireland

Background: Reports from individual referral centres suggest that a significant proportion of children with inflammatory bowel disease (IBD) present after prolonged delays and with impaired growth. Aims: To prospectively document...

Risk of inflammatory bowel disease attributable to smoking, oral contraception and breastfeeding in Italy: a nationwide case-control study. Cooperative Investigators of the Italian Group for the Study of the Colon and the Rectum (GISC).

Using data from a case-control study carried out in Italy 1989-1992, we estimated the odds ratios (OR) and the population attributable risks (AR) for inflammatory bowel diseases (IBD) in relation to smoking, oral contraception and breastfeeding in infancy. The study focused on 819 cases of IBD (594 ulcerative colitis: UC; 225 Crohn's disease: CD) originating from populations resident in 10 Italian areas, and age-sex matched paired controls. Compared with non-smokers, former smokers were at increased risk of UC (OR = 3.0; 95% confidence interval [CI]: 2.1-4.3), whereas current smokers were at increased risk of CD (OR = 1.7; 95% CI: 1.1-2.6). Females who reported use of oral contraceptives for at least one month before onset of symptoms had a higher risk of CD (OR = 3.4; 95% CI: 1.0-11.9), whereas no significant risk was observed for UC. Lack of breastfeeding was associated with an increased risk of UC (OR = 1.5; 95% CI: 1.1-2.1) and CD (OR = 1.9; 95% CI: 1.1-3.3). Being a 'former smoker' was the factor with the highest attributable risk of UC both in males (AR = 28%; 95% CI: 20-35 %) and in females (AR = 12%; 95% CI: 5-18%). Smoking was the factor with the highest attributable risk for CD in males (AR = 31%; 95% CI: 11-50%). Lack of breastfeeding accounted for the highest proportion of CD in females (AR = 11%; 95% CI: 1-22%). Oral contraceptive use accounted for 7% of cases of UC and for 11% of cases of CD. Taken together, the considered factors were responsible for a proportion of IBD ranging from 26% (CD females) to 36% (CD males). It is concluded that other environmental and genetic factors may be involved in the aetiology of IBD.

GONADAL FUNCTION IN YOUNG ADULTS AFTER SURGICAL TREATMENT OF CRYPTORCHIDISM

47 men who had been surgically treated for unilateral (UC,n=32) and bilateral cryptorchidism (BC,n=15) at 5-14 yrs were studied on follow-up at 16-28 yrs. In UC the volume of the operated testis was 11.9±0.7 ml (mean ± SEN) and of the contralateral testis 15.8± 0.7 ml. In BC the mean testicular volume was 11.3±0.9 ml. Sperm count was below 40 millions/ml in 12 UC (n=23) and 9 BC (n=13) with 5 of them below 1 million/ml. In all patients plasma LH and FSH were measured before and 10-120 tnin. after LHRH (25 ug/m2 i.v.). Basal FSH values were elevated in 5 UC and 10 BC, FSH response to LHRH was excessive in 2 UC and 8 BC. Basal LH values were within normal limits in all patients, but a high LH response was observed in 6 UC and 3 BC. Plasma testosterone was normal in all but 3 cases (2 UC, 1BC) where subnormal levels were found. This study reveals a high incidence of functional impairment of the germinal epithelium in cryptorchidism with compromised fertility in most cases with BC. Leydig cell function is affected in only a few cases of both UC and BC.