The utility of biomarkers in diagnosis of aspirin exacerbated respiratory disease.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is a distinct eosinophilic phenotype of severe asthma with accompanying chronic rhinosinusitis, nasal polyposis, and hypersensitivity to aspirin. Urinary 3-bromotyrosine (uBrTyr) is a noninvasive marker of eosinophil-catalyzed protein oxidation. The lack of in vitro diagnostic test makes the diagnosis of AERD difficult. We aimed to determine uBrTyr levels in patients with AERD (n = 240) and aspirin-tolerant asthma (ATA) (n = 226) and to assess whether its addition to urinary leukotriene E4 (uLTE4) levels and blood eosinophilia can improve the prediction of AERD diagnosis. METHODS: Clinical data, spirometry and blood eosinophilis were evaluated. UBrTyr and uLTE4 levels were measured in urine by HPLC and ELISA, respectively. RESULTS: Both groups of asthmatics (AERD, n = 240; ATA, n = 226) had significantly higher uBrTyr, uLTE4 levels, and blood eosinophils than healthy controls (HC) (n = 71) (p < 0.05). ULTE4 levels and blood eosinophils were significantly higher in AERD as compared to ATA (p = 0.004, p < 0.0001, respectively). whereas uBrTyr levels were not significantly different between both asthma phenotypes (p = 0.34). Asthmatics with high levels of uBrTyr (> 0.101 ng/mg Cr), uLTE4 levels (> 800 pg/mg Cr) and blood eosinophils (> 300 cells/ul) were 7 times more likely to have AERD.. However, uBrTyr did not increase the benefit for predicting AERD when uLTE4 and blood eosinophils were already taken into account (p = 0.57). CONCLUSION: UBrTyr levels are elevated both in AERD and ATA as compared to HC, but they could not differentiate between these asthma phenotypes suggesting a similar eosinophilic activation. The addition of uBrTyr to elevated uLTE4 levels and blood eosinophils did not statistically enhance the prediction of AERD diagnosis.

TH1 and TH2 cytokine data in insulin secretagogues users newly diagnosed with breast cancer.

Stimulation of insulin production by insulin secretagogue use may impact T helper cells' cytokine production. This dataset presents the relationship between baseline insulin secretagogues use in women diagnosed with breast cancer and type 2 diabetes mellitus, the T-helper 1 and 2 produced cytokine profiles at the time of breast cancer diagnosis, and subsequent cancer outcomes. A Pearson correlation analysis evaluating the relationship between T-helper cytokines stratified by of insulin secretagogues use and controls is also provided.

Data report on inflammatory C-C chemokines among insulin-using women with diabetes mellitus and breast cancer.

Injectable insulin use may interfere with pro-inflammatory cytokines' production and, thus, play a role in the activation of tumor-associated macrophages - a process mainly influenced by inflammatory C-C chemokines. The data presented shows the relationship between pre-existing use of injectable insulin in women diagnosed with breast cancer and type 2 diabetes mellitus, the inflammatory C-C chemokine profiles at the time of breast cancer diagnosis, and subsequent cancer outcomes. A Pearson correlation analysis stratified by insulin use and controls is also provided. We present the observed relationship between the investigated C-C chemokines and between each of these biomarkers and previously reported adipokines levels in this study population [1].

Circulating growth factors data associated with insulin secretagogue use in women with incident breast cancer.

Oral drugs stimulating insulin production may impact growth factor levels. The data presented shows the relationship between pre-existing insulin secretagogues use, growth factor profiles at the time of breast cancer diagnosis and subsequent cancer outcomes in women diagnosed with breast cancer and type 2 diabetes mellitus. A Pearson correlation analysis evaluating the relationship between growth factors stratified by diabetes pharmacotherapy and controls is also provided.

Dataset on granulopoiesis- and lymphopoiesis-stimulating cytokine levels in insulin secretagogue users with incident breast cancer.

GM-CSF and G-CSF are widely used for their benefit in reducing chemotherapy-associated neutropenia. However, whether GM- or G-CSF administration could have tumorigenic or pro-metastatic effects or whether insulin resistance could negatively impact such effects is not known. Their ability to stimulate monocyte production at the same time with the highly sought after neutrophils' production, enables an enhanced potential for activation of tumor-associated macrophages. At the same time, IL-7 remains the main driver of B and T cell differentiation and maturation, a process linked to the development of insulin resistance and response to diabetes pharmacotherapy. Insulin secretagogues have the potential to interfere with the hematopoiesis process, respectively with the formation of lineages that may lead to a tumorigenic or pro-metastatic phenotype, but this relationship has not been yet investigated. The data presented here shows the relationship between pre-existing use of insulin secretagogues in women diagnosed with breast cancer and type 2 diabetes mellitus, the GM-CSF, G-CSF and IL-7 cytokine profiles at the time of breast cancer diagnosis, and subsequent cancer outcomes. A Pearson correlation analysis evaluating the relationship between investigated cytokines stratified by secretagogue use and controls, and interferon is also provided.

TH1 and TH2 cytokines dataset in insulin users with diabetes mellitus and newly diagnosed breast cancer.

Exogenous insulin use may interfere with the T helper cells' cytokine production. This dataset presents the relationship between pre-existing use of injectable insulin in women diagnosed with breast cancer and type 2 diabetes mellitus, the T-helper 1 and 2 produced cytokine profiles at the time of breast cancer diagnosis, and subsequent cancer outcomes. A Pearson correlation analysis evaluating the relationship between T-helper cytokines stratified by of insulin use and controls is also provided.

Insulin use, hormone receptor status and hematopoietic cytokines׳ circulation in women with diabetes mellitus and breast cancer.

Granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage colony-stimulating factor (GM-CSF) are cytokines of particular interest in oncology from the perspective of neutropenia management (Mehta et al., 2015 [1]) and also as indirect activators of tumor-associated macrophages and modifiers of tumor microenvironment. Associated with poor breast cancer survival and unfavorable hormone receptor status (Wintrob et al., 2017 [2]), insulin may also influence hematopoiesis, thus interfering with colony stimulating factor production. Although G-CSF has been linked to exacerbating insulin resistance (Ordelheide et al., 2016 [3]), thus far no study linked insulin treatment and hematopoietic cytokines production. Additionally, IL-7 is the primary driver of T and B cell differentiation, maturation, and response (Corfe and Paige, 2012 [4]) and its elevated levels have been associated with poor prognosis in breast cancer. The data presented here is among the first to show a relationship between pre-existing use of injectable insulin in women diagnosed with breast cancer and type 2 diabetes mellitus, hematopoietic cytokine profiles at time of breast cancer diagnosis, and subsequent cancer outcomes. A Pearson correlation analysis evaluating the relationship between G-CSF, GM-CSF, and IL-7 stratified by insulin use, controls, as well as by estrogen and progesterone receptor status is also provided.

Insulin secretagogue use and circulating inflammatory C-C chemokine levels in breast cancer patients.

Monocytes' infiltration into the tumor tissue and their activation to tumor-associated macrophages is an essential step in tumor development, also playing a critical role in an eventual metastasis. Stimulation of endogenous insulin production by oral insulin secretagogue treatment has the potential to interfere with the production and release of C-C chemokines, a group of potent inflammatory cytokines acting as monocyte chemo-attractants and influencing their behavior in the tumor microenvironment. Studied plasma samples were collected under a previously reported study design involving a population of women diagnosed with breast cancer presenting with or without type 2 diabetes mellitus at the time of breast cancer diagnosis (Wintrob et al., 2017, 2016) [1,2]. The data presented here shows the relationship between pre-existing use of insulin secretagogue, the inflammatory C-C chemokine profiles at the time of breast cancer diagnosis, and subsequent cancer outcomes. A Pearson correlation analysis stratified by secretagogue use and controls was implemented to evaluate the relationship between the investigated biomarkers and respectively each of these biomarkers and the other relevant reported cytokine datasets derived from the same patient population (Wintrob et al., 2017, 2016) [1,2].

Dataset on growth factor levels and insulin use in patients with diabetes mellitus and incident breast cancer.

Growth factor profiles could be influenced by the utilization of exogenous insulin. The data presented shows the relationship between pre-existing use of injectable insulin in women diagnosed with breast cancer and type 2 diabetes mellitus, the growth factor profiles at the time of breast cancer diagnosis, and subsequent cancer outcomes. A Pearson correlation analysis evaluating the relationship between growth factors stratified by of insulin use and controls is also provided.

Insulin use, adipokine profiles and breast cancer prognosis.

BACKGROUND: Type-2 diabetes mellitus (T2DM) and breast cancer (BC) share common cytokine signaling changes resultant from adipose tissue dysfunction. This modified adipokine signaling was shown to be directly associated with changes in the body mass index (BMI) and diet and it is expected to also be influenced by T2DM pharmacotherapy. We evaluated the relationship between pre-existing diabetes treatment, circulating adipokine levels at cancer diagnosis, and long-term outcomes. METHODS: All incident BC cases were reviewed (01/01/2003-12/31/2009, N=2194). Each of the subjects with baseline T2DM (cases) was matched with two other subjects without T2DM (controls) based on the following criteria: age, BMI, ethnicity, menopausal status and tumor stage. All cases and controls with available baseline plasma and tumor biopsies, and being surgery and BC treatment naïve, were included (N1=97, N2=194). Clinical history and vital status were documented. Adipokine levels (adiponectin, leptin, TNF-α, CRP, IL-1ß, IL-1Ra, IL-6, and C-peptide) were assessed by either ELISA or Luminex® assays. Cancer outcomes were assessed by Kaplan-Meier analysis; associations between categorical variables were assessed by Fisher's exact test, categorical and continuous variables by Kruskal-Wallis or Wilcoxon Rank-Sum test, where appropriate. Multivariate adjustments (MVP, multivariate p-value) were performed accounting for age, tumor stage, BMI, estrogen receptor (ER) status and cumulative comorbidity. All biomarker correlations were assessed by the Pearson method. Utilization of insulin and insulin secretagogues was associated with ER (-) phenotype (p=0.008, p=0.043) and poorer BC outcomes (p=0.012, p=0.033). Insulin users were found to have lower C-peptide and higher IL-6, TNF-α and CRP levels, of which elevated CRP and TNF-α were associated with poorer BC outcomes (p=0.003, MVP=0.210). Insulin remarked by higher leptin levels as compared to controls (p=0.052), but did not differ significantly from non-users. Although lower adiponectin levels were observed among non-insulin users as compared to controls (p<0.001, MVP=0.006), insulin use seemed to have restored adiponectin production. C-peptide levels were lower among insulin users as compared to non-users (p<0.001, MVP<0.001) and approached levels comparable with those of the controls. In the overall dataset, C-peptide lower than 0.75ng/ml were strongly associated with poorer survival (p=0.007, MVP=0.002). Among insulin users, C-peptide levels were inversely correlated with IL-1ß and IL-1Ra levels only after full adjustment (p=0.012, p=0.030); the correlation was unremarkable in other groups. CONCLUSION: Insulin use is associated with elevated leptin, CRP, TNFα, and lower C-peptide and also linked to poor BC outcomes. More research is needed to verify these findings; however, we are among the first to correlate pharmacotherapy use, measures of adipose tissue dysfunction and cancer outcomes.

Circulating adipokines data associated with insulin secretagogue use in breast cancer patients.

Oral drugs stimulating endogenous insulin production (insulin secretagogues) may have detrimental effects on breast cancer outcomes. The data presented shows the relationship between pre-existing insulin secretagogues use, adipokine profiles at the time of breast cancer (BC) diagnosis and subsequent cancer outcomes in women diagnosed with BC and type 2 diabetes mellitus (T2DM). The Pearson correlation analysis evaluating the relationship between adipokines stratified by T2DM pharmacotherapy and controls is also provided. This information is the extension of the data presented and discussed in "Insulin use, adipokine profiles and breast cancer prognosis" (Wintrob et al., in press) [1].

Pattern of Inflammation on Surveillance Colonoscopy Does Not Predict Development of Colitis-associated Neoplasia.

BACKGROUND: Identification of colonoscopic features which increase colitis-associated neoplasia risk in patients with ulcerative colitis (UC) may allow patient risk stratification. Our objective was to investigate whether colonoscopic features correlate with the risk of developing colitis-associated neoplasia in patients with UC on surveillance. METHODS: In this retrospective case-control study, patients with UC who underwent surveillance colonoscopies from 1998 to 2011 were included. Patients with UC with neoplasia were compared with a matched control group of patients with UC without neoplasia in a 1:3 ratio. RESULTS: A total of 111 eligible patients with UC with colon neoplasia were compared with 356 patients with UC without colon neoplasia. On univariate analysis, colitis-associated neoplasia was associated with male gender (odds ratio [OR] = 2.58, 95% confidence interval [CI]: 1.71-3.89, P ≤ 0.001) and smoking history (OR = 1.62, 95% CI: 1.1-2.39, P = 0.045) but not with colonoscopic features, including tubular colon/shortened colon, scarring, segment of severe inflammation, inflammatory polyps, colonic stricture, or macroscopically normal appearance colonoscopy. In multivariate analysis, only male gender (OR = 2.68, 95% CI: 1.77-4.08, P ≤ 0.001) was found to be associated with an increased risk, whereas the use of 5-aminosalicylates was associated with a decreased risk for colitis-associated neoplasia (OR = 0.51, 95% CI: 0.31-0.84, P = 0.009). CONCLUSIONS: In patients with UC, colonoscopic features especially on standard-definition white-light colonoscopy did not appear to reliably predict the development of colitis-associated neoplasia. This will leave room for image-enhanced endoscopy technology and molecular markers for the early and accurate detection of colitis-associated neoplasia.

Comparison of outcomes for patients with primary sclerosing cholangitis associated with ulcerative colitis and Crohn's disease.

BACKGROUND: The comparative outcomes of ulcerative colitis (UC) and Crohn's disease (CD) in patients with primary sclerosing cholangitis (PSC) are unclear; the aim of our study was to make an objective comparison. METHODS: A total of 273 patients with PSC and inflammatory bowel disease (223 with UC and 50 with CD) were included. Clinical and demographic variables were obtained. RESULTS: The PSC risk score was similar for both groups. The median follow-up period in patients with PSC-UC was 12 years (range 0-38) and that for PSC-CD was 14 years (range 1-36). The median number of disease flares per year was higher in PSC-UC patients than in the PSC-CD group [1vs.0 (ranges 0-20 and 0-9, respectively); P < 0.001]. More patients with UC developed colon neoplasia than CD (35.9% vs.18%; P = 0.009). On proportional hazards analysis for the risk of colectomy, UC patients had a 12% higher risk for colectomy [hazard ratio (HR) = 0.88; 95% confidence interval (CI) 0.51-1.51; P = 0.64]. Liver transplantation for PSC was associated with decreased risk (HR = 0.57; 95% CI 0.37-0.89; P = 0.013), while colon neoplasia increased the risk (HR = 3.83; 95% CI 2.63-5.58; P < 0.001) for colectomy. On proportional hazards analysis for the risk of colon neoplasia, UC patients had 56% higher risk of developing colon neoplasia than CD (HR = 0.44; 95% CI 0.16-1.25; P = 0.12). CONCLUSIONS: PSC patients with CD appear to be associated with a lower risk of colon neoplasia and colectomy than PSC patients with UC.

Volatile Organic Compounds in Urine for Noninvasive Diagnosis of Malignant Biliary Strictures: A Pilot Study.

BACKGROUND: The use of volatile organic compounds (VOCs) in bile was recently studied and appeared promising for diagnosis of malignancy. Noninvasive diagnosis of malignant biliary strictures by using VOCs in urine has not been studied. AIM: To identify potential VOCs in urine to diagnose malignant biliary strictures. METHODS: In this prospective cross-sectional study, urine was obtained immediately prior to ERCP from consecutive patients with biliary strictures. Selected-ion flow-tube mass spectrometry was used to analyze the concentration of VOCs in urine samples. RESULTS: Fifty-four patients with biliary strictures were enrolled. Fifteen patients had malignant stricture [six cholangiocarcinoma (CCA) and nine pancreatic cancer], and 39 patients had benign strictures [10 primary sclerosing cholangitis (PSC) and 29 with benign biliary conditions including chronic pancreatitis and papillary stenosis]. The concentration of several compounds (ethanol and 2-propanol) was significantly different in patients with malignant compared with benign biliary strictures (p < 0.05). Using receiver operating characteristic curve analysis, we developed a model for the diagnosis of malignant biliary strictures adjusted for age and gender based on VOC levels of 2-propranol, carbon disulfide, and trimethyl amine (TMA). The model [-2.4191 * log(2-propanol) + 1.1617 * log(TMA) - 1.2172 * log(carbon disulfide)] ≥ 7.73 identified the patients with malignant biliary stricture [area under the curve (AUC = 0.83)], with 93.3 % sensitivity and 61.5 % specificity (p = 0.009). Comparing patients with CCA and PSC, the model [38.864 * log(ethane) - 3.989 * log(1-octene)] ≤ 169.9 could identify CCA with 80 % sensitivity and 100 % specificity (AUC = 0.9). CONCLUSIONS: Measurement of VOCs in urine may diagnose malignant biliary strictures noninvasively.

Comparative effectiveness of pyruvate kinase M2 in bile, serum carbohydrate antigen 19-9, and biliary brushings in diagnosing malignant biliary strictures.

BACKGROUND: The role of M2-PK (pyruvate kinase) in bile has not been studied in comparison with brushings and carbohydrate antigen (CA) 19-9 in the diagnosis of malignant biliary strictures. AIM: To compare the diagnostic accuracy of biliary M2-PK with cytology and serum CA 19-9 METHODS: In this prospective cross-sectional study, bile was aspirated in 74 patients (discovery and validation cohort) undergoing endoscopic retrograde cholangiopancreatography. Levels of M2-PK were measured in bile and compared to brushings for cytology and CA 19-9. RESULTS: In the discovery cohort, the median bile M2-PK levels were significantly elevated in patients with malignant biliary strictures [187.9 U/l (interquartile range (IQR) 3.5, 3626.8)] compared to those with benign biliary conditions and primary sclerosing cholangitis [0 U/l (IQR 0, 15)] (P = 0.007). A M2-PK cutoff value of 109.1 U/l distinguished malignant from benign conditions with a sensitivity and specificity of 52.9 and 94.1 %, respectively, and area under curve (AUC) of 0.77. The sensitivity of CA 19-9 and brushings in diagnosing cancer was 52.9 % and 11.1 % and specificity 94.1 and 100 %, respectively. The presence of elevated M2-PK >109.1 U/l or CA 19-9 >33 U/ml or positive brushing was 88.2 % sensitive and 88.2 % specific, AUC of 0.89 in the diagnosis of malignancy. The diagnostic accuracy was confirmed in the validation cohort. CONCLUSIONS: As a stand-alone factor, none of the markers were able to distinguish benign from malignant biliary strictures with a high sensitivity. However, a combination was highly sensitive in diagnosing malignant biliary strictures.

Volatile organic compounds in bile for early diagnosis of cholangiocarcinoma in patients with primary sclerosing cholangitis: a pilot study.

BACKGROUND: The diagnosis of cholangiocarcinoma (CCA) in patients with primary sclerosing cholangitis (PSC) is particularly difficult. The role of volatile organic compounds (VOCs) for diagnosis of CCA in patients with PSC is not known. OBJECTIVE: Our aim was to identify potential VOCs in the headspaces (gas above the sample) in bile that may predict CCA in patients with PSC. DESIGN: Prospective cross-sectional study. SETTING: Referral center. PATIENTS: A total of 32 patients undergoing ERCP for PSC and for CCA complicating PSC. INTERVENTIONS: ERCP, bile aspiration. MAIN OUTCOME MEASUREMENTS: Selected ion flow tube mass spectrometry was used to analyze the concentration of 22 prevalent VOCs in bile samples. Logistic regression analysis was performed to build a predictive model for diagnosis of CCA. RESULTS: Levels of several compounds (ethanol, acrylonitrile, acetonitrile, acetaldehyde, benzene, carbon disulfide, dimethyl sulfide, 2-propranolol) were significantly different in patients with CCA complicating PSC compared with those having PSC (P < .05). By using receiver operating characteristic curve analysis, we developed a model for the diagnosis of CCA adjusted for age and sex based on VOC levels of acrylonitrile, 3-methyl hexane, and benzene. The model (2.3239*log [acrylonitrile] + 0.9871*log [3-methyl hexane] + 0.8448*log [benzene]) < -0.12 identified the patients with CCA (area under the curve [AUC] = 0.89), with 90.5% sensitivity and 72.7% specificity (P = .02). LIMITATIONS: Sample size. CONCLUSION: The measurement of VOCs in biliary fluid may be useful to diagnose CCA in patients with PSC. A larger study with a longitudinal study design is required to confirm our pilot observations to diagnose CCA early in patients with PSC. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01565460.).

Volatile organic compounds in bile can diagnose malignant biliary strictures in the setting of pancreatic cancer: a preliminary observation.

BACKGROUND: Ascertaining the nature of biliary strictures is challenging. The role of volatile organic compounds (VOCs) in bile in determining the cause of biliary strictures is not known. OBJECTIVE: To identify potential VOCs in the headspaces (gas above the sample) of bile in patients with malignant biliary strictures from pancreatic cancer. DESIGN: Prospective cross-sectional study. SETTING: Referral center. PATIENTS: Prospective study in which bile was aspirated in 96 patients undergoing ERCP for benign and malignant conditions. MAIN OUTCOME MEASUREMENTS: Selected ion flow tube mass spectrometry (VOICE200R SIFT-MS instrument; Syft Technologies Ltd, Christchurch, New Zealand) was used to analyze the headspace and to build a predictive model for pancreatic cancer. RESULTS: The headspaces from 96 bile samples were analyzed, including 24 from patients with pancreatic cancer and 72 from patients with benign biliary conditions. The concentrations of 6 compounds (acetaldehyde, acetone, benzene, carbon disulfide, pentane, and trimethylamine [TMA]) were increased in patients with pancreatic cancer compared with controls (P < .05). By using receiver-operating characteristic curve analysis, we developed a model for the diagnosis of pancreatic cancer based on the levels of TMA, acetone, isoprene, dimethyl sulfide, and acetaldehyde. The model [10.94 + 1.8229* log (acetaldehyde) + 0.7600* log (acetone) - 1.1746* log (dimethyl sulfide) + 1.0901* log (isoprene) - 2.1401 * log (trimethylamine) ≥ 10] identified the patients with pancreatic cancer (area under the curve = 0.85), with 83.3% sensitivity and 81.9% specificity. LIMITATIONS: Sample size. CONCLUSIONS: The measurement of biliary fluid VOCs may help to distinguish malignant from benign biliary strictures. Further studies are warranted to validate these observations. (Clinical Trial Registration Number NCT01565460.).

Evaluation of the pharmacokinetics and pharmacodynamics of liposomal amikacin for inhalation in cystic fibrosis patients with chronic pseudomonal infections using data from two phase 2 clinical studies.

The pharmacokinetic-pharmacodynamic (PK-PD) relationships between serum exposure measures of liposomal amikacin for inhalation (LAI) and the change in pulmonary function test (PFT) measures and number of CFU from baseline were evaluated in cystic fibrosis (CF) patients chronically infected with Pseudomonas aeruginosa. A dose of 70, 140, 280, or 560 mg of LAI or placebo was administered to CF patients once daily for 28 days. PFTs and sputum samples for microbiology were assessed on days 7, 14, 21, 28, 35 (for log10 CFU), and 56 (for PFTs). Serum, urine, and sputum samples were collected for PK evaluation. The relationships between efficacy endpoints (relative change in forced expiratory volume in 1 s [FEV1 {expressed in liters}] and FEV1% predicted and the absolute change in log10 CFU of P. aeruginosa from baseline) and exposure measures (dose, day 1 area under the curve [AUC], dose/MIC ratio, and day 1 AUC/MIC ratio) and baseline MIC value were assessed. The serum and urine PK data were best fit by a 3-compartment model (lung, serum, and urine) with linear clearance and interoccasional variation on total and renal clearance. Significant univariable relationships between dose or day 1 AUC and the relative change in PFT measures (P≤0.017) or the absolute change in log10 CFU from baseline (P≤0.037) on the study days were identified. Repeated-measures mixed-effects models, which showed dose- and AUC-related improvements for each efficacy endpoint (P≤0.041), predicted the observed data well. The increases in the relative change in FEV1 and FEV1% predicted of 11% and 9.9%, respectively, and a 1.23-log10 CFU reduction per 560 mg of LAI estimated on day 7 were comparable to the observed increases of 10.7% and 10.3%, respectively, and a 1.24-log10 CFU reduction on the same day. The model-estimated PFT effects were predicted to be sustained to day 28. An additional 0.451-log10 CFU reduction (P=0.022) was estimated on day 14 relative to day 7, with a persistence of effect predicted to day 35.

Comparable pouch retention rate between pediatric and adult patients after restorative proctocolectomy and ileal pouches.

BACKGROUND & AIMS: We compared long-term outcomes between adult and pediatric patients with inflammatory bowel disease (IBD) who underwent restorative proctocolectomy with ileal pouch-anal anastomosis. METHODS: We performed a retrospective study that analyzed data from consecutive patients with ileal pouches who presented to the subspecialty Pouch Center at the Cleveland Clinic from 2002-2011. Pouch outcomes of 104 pediatric patients (having pouch surgery at age <18 years; 53 male) were compared with those of 1135 adults (having pouch surgery at an age 18 years or older; 632 male). RESULTS: Pediatric patients had a shorter duration from time of IBD diagnosis to colectomy than adult patients. Fewer pediatric than adult patients had a history of smoking, concomitant extraintestinal manifestations, or dysplasia as the indication for colectomy. However, pediatric patients had higher rates of pouch procedure-related complications, postoperative pouch-associated hospitalization, and postoperative use of anti-tumor necrosis factor (TNF) agents. In multivariate analysis, risk factors for pouch failure included preoperative use of anti-TNF agents (hazard ratio [HR], 1.81; 95% confidence interval [CI], 1.05-3.13; P = .032), postoperative use of anti-TNF agents (HR, 2.07; 95% CI, 1.31-3.27; P = .002), Crohn's disease of the pouch (HR, 2.21; 95% CI, 1.28-3.82; P = .005), pouch procedure-related complications (HR, 2.68; 95% CI, 1.55-4.64; P < .001), and postoperative pouch-associated hospitalization (HR, 25.20; 95% CI, 14.44-43.97; P < .001). Being a pediatric patient was not significantly associated with pouch failure in univariate or multivariate analyses (HR, 0.6; 95% CI, 0.32-1.16; P = .13). CONCLUSIONS: On the basis of an analysis of patients with IBD who underwent restorative proctocolectomy and presented at a subspecialized Pouch Center, patients who had the surgery at a pediatric age tend to have a higher incidence of postoperative pouch complications than adults. However, long-term rates of pouch retention were comparable.