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.

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.).

Risk of comorbidities and outcomes in patients with lower gastrointestinal bleeding - a nationwide study.

BACKGROUND: The impact of comorbidities on outcomes of patients with lower gastrointestinal bleeding (LGIB) remains unknown. OBJECTIVE: Investigate the prevalence of comorbidities and impact on outcomes of patients with LGIB. METHODS: The Nationwide Inpatient Sample 2010 was used to identify patients who had a primary discharge diagnosis of LGIB based on International Classification of Diseases, the 9th revision, clinical modification codes. The presence of comorbid illness was assessed using the Elixhauser index. Logistic regression models were used to assess the contributions of the individual Elixhauser comorbidities to predict in-hospital mortality. RESULTS: A total of 58,296 discharges with LGIB were identified. The overall mortality was 2.3 %. Among the patients who underwent colonoscopy, 17.3 % of patients had therapeutic intervention. As the number of comorbidities increased (i.e., 0, 1, 2, or >3), mortality increased (1.7, 2.0, 2.4, and 2.4 %, respectively). The mortality rate was highest in patients >65 years of age (2.7 %). Patients >65 years of age with two or more comorbidities had a mortality rate of 5 % as compared to 2.6 % in those with less than two comorbidities. Congestive heart failure (odds ratio, 1.67 [95 % confidence interval, 1.48-1.95]), liver disease (2.64 [1.83-3.80]), renal failure (1.99 [1.70-2.33]), and weight loss (2.66 [2.27-3.12]) were associated with a significant increase in mortality rate. Comorbidities increased hospital stay and costs. CONCLUSIONS: Comorbidities were associated with increased the risk of mortality and health care utilization in patients with LGIB. Identification of comorbidities and development of risk-adjustment tools may improve the outcome of patients with LGIB.

Endoscopic resection of large sporadic non-ampullary duodenal polyps: efficacy and long-term recurrence.

BACKGROUND: Endoscopic resection is an alternative to surgery for removal of large duodenal polyps. There are limited data on the safety, efficacy, and long-term recurrence data after endoscopic resection of sporadic, non-ampullary, and large duodenal polyps. OBJECTIVE: Our aim was to evaluate the safety and short-term outcomes of the endoscopic removal of the large sporadic duodenal polyps and to determine long-term risk of recurrence and factors predicting recurrence on follow-up. METHODS: Patients with large (>10 mm) sporadic non-ampullary duodenal polyps underwent endoscopic resection from 2001 to 2012 at the Cleveland Clinic. Patients underwent endoscopic polypectomy and argon plasma coagulation. The main outcome measurements were complete polypectomy, complications, short- and long-term recurrence. RESULTS: A total of 54 patients were included. The mean patient age was 66.4 years. The mean polyp size was 15.1 ± 5.4 mm. Most polyps (N = 48, 88.9 %) were sessile polyps. The median follow-up time was 10.8 (range 0.5-120) months. Most lesions were located in the second part of the duodenum (N = 41, 75.9 %). Adenomas were found in 46 (85.2 %) of lesions overall. Tubular adenoma was the most common histology type found in 33 cases (71.7 %). Tubulovillous and villous were found in 12 (26.1 %) and 1 (2.2 %) cases, respectively. On follow-up, 50 (92.6 %) achieved complete resection with tumor free margins post resection. The 30-day risk of major complications was 5.6 % (N = 3), 1 with perforation and 2 with delayed bleeding. Recurrence was documented in 29 % (N = 16) of patients. All recurrences were managed endoscopically except for one patient who required surgery. The recurrence rate was higher for patients who had villous component in their adenomas compared to those with tubular alone (p = 0.03). CONCLUSIONS: Endoscopic resection is effective for treating large duodenal adenomas. Adenomas with villous features are more likely to recur. Almost all recurrences can be managed endoscopically.

Predictors for detection of cancer in patients with indeterminate biliary stricture and atypical cells on endoscopic retrograde brush cytology.

OBJECTIVE: The management of atypical cells on endoscopic retrograde brush cytology (ERBC) in patients with indeterminate biliary stricture is unclear. This study aimed to investigate the detection of cancer (pancreatic and biliary carcinoma) in patients with atypical cells on ERBC and the factors predicting it. METHODS: From a prospectively maintained cytology database in a tertiary care center, patients with indeterminate biliary stricture and atypical cells on ERBC from 1996 to 2012 were studied. The date of the initial ERBC with atypical cells was identified as time zero. The primary outcome was to study the incidences and Kaplan-Meier estimates for detecting cancer. RESULTS: In all, 104 patients with 182.8 person-years of follow-up were identified. In 38 (36.5%) patients cancer was detected (19 cholangiocarcinoma, 15 pancreatic cancer, three ampullary cancer and one gallbladder carcinoma) over a mean follow-up of 4.4 months. On Cox regression analysis, the presence of clinical jaundice (hazard ratio [HR] 4.08, 95% CI 1.41-11.8), active alcohol consumption (HR 7.33, 95% CI 1.85-29.1) and elevated carbohydrate antigen 19-9 (CA19-9) level (>33 U/mL) (HR 8.42, 95% CI 1.75-40.6) at the time of ERBC were associated with increased risk for the detection of cancer. Detection of cancer was more common during the first 6 months of follow-up than at any time period thereafter. CONCLUSION: Elevated CA19-9 level, the presence of clinical jaundice and current alcohol consumption are associated with increased detection of cancer in patients with indeterminate biliary stricture and atypical cells on ERBC.

Increased mortality with peptic ulcer bleeding in patients with both compensated and decompensated cirrhosis.

BACKGROUND: Cirrhosis is associated with worse outcomes in peptic ulcer bleeding (PUB). There are no population-based studies from the United States on the impact of cirrhosis on PUB outcomes. OBJECTIVE: To investigate the impact of cirrhosis on outcomes of patients with PUB. DESIGN: Cross-sectional study. SETTING: Nationwide Inpatient Sample 2009. PATIENTS: International Classification of Diseases, the 9th revision, codes were used to identify patients with PUB and cirrhosis. The control group was patients with PUB without cirrhosis. MAIN OUTCOME MEASUREMENTS: In-hospital mortality, length of stay, and hospitalization costs. RESULTS: A total of 96,887 discharges with PUB as a diagnosis were identified-3574 with PUB and cirrhosis and 93,313 with PUB alone without cirrhosis. Mortality of PUB with concomitant cirrhosis was higher than in the control group without cirrhosis (5.5% vs 2%; P = .01); decompensated cirrhosis had higher mortality than did compensated cirrhosis (6.6% vs 3.9%; P = .01). In multivariate analysis, the presence of cirrhosis independently increased mortality (adjusted odds ratio (aOR) 3.3; 95% confidence interval [CI], 2.2-4.9). Stratified analysis showed that decompensated cirrhosis (aOR 4.4; 95% CI, 2.6-7.3) had higher mortality than compensated cirrhosis (aOR 1.9; 95% CI, 1.04-3.6). There was no difference in the proportion of patients who underwent endoscopy within 24 hours (51.9% vs 51.1%; P = .68) between those with cirrhosis and controls. Patients with cirrhosis received less surgical intervention (aOR 0.8; 95% CI, 0.6-0.9) compared with controls. Hospitalization costs also were increased in patients with decompensated cirrhosis. LIMITATIONS: Administrative data set. CONCLUSION: Both decompensated and compensated cirrhosis are associated with increased mortality in patients with PUB.

Timing of colonoscopy and outcomes in patients with lower GI bleeding: a nationwide population-based study.

BACKGROUND: The role of urgent colonoscopy in lower GI bleeding (LGIB) remains controversial. Population-based studies on LGIB outcomes are lacking. OBJECTIVE: To investigate the impact of the timing of colonoscopy on outcomes of patients with LGIB. DESIGN: Cross-sectional study. SETTING: Nationwide Inpatient Sample 2010. PATIENTS: International Classification of Diseases, Ninth Revision, Clinical Modification codes identified patients with LGIB who underwent colonoscopy. MAIN OUTCOME MEASUREMENTS: In-hospital mortality, length of stay, and hospitalization costs in patients who underwent early (≤24 hours) or delayed (>24 hours) colonoscopy. RESULTS: A total of 58,296 discharges with LGIB were identified; 22,720 had a colonoscopy performed during the hospitalization. A total of 9156 patients had colonoscopy performed within 24 hours (early colonoscopy), and 13,564 had colonoscopy performed after 24 hours (delayed colonoscopy). There was no difference in mortality in patients with LGIB who had early versus delayed colonoscopy (0.3% vs 0.4%, P = .24). However, patients who underwent early colonoscopy had a shorter length of hospital stay (2.9 vs 4.6 days, P < .001), decreased need for blood transfusion (44.6% vs 53.8%, P < .001), and lower hospitalization costs ($22,142 vs $28,749, P < .001). On multivariate analysis, timing of colonoscopy did not affect mortality (adjusted odds ratio 1.5; 95% confidence interval, 0.7-2.7). On multivariate analysis, delayed colonoscopy was associated with an increase in the length of hospital stay by 1.6 days and an increase in hospitalization costs of $7187. LIMITATIONS: Administrative dataset. CONCLUSIONS: Early colonoscopy within 24 hours is associated with decreased length of hospital stay and hospitalization costs in patients with LGIB.

Factors associated with 30-day readmission and long-term efficacy of enteral stent placement for malignancy.

BACKGROUND: Readmissions to the hospital within 30 days of discharge (30-day readmission rate) may impact stent use in palliative treatment of cancer. OBJECTIVE: Our objective was to investigate the incidence of readmission and factors predicting readmissions and long-term outcomes in patients with self-expanding metal stents (SEMS) placed for malignant obstruction. METHODS: Retrospective analysis of all patients who underwent placement of SEMS from 2007 to 2012 for malignant esophageal, gastroduodenal, and colonic obstruction. Incidence and variables associated with 30-day readmission and long-term outcomes were determined. RESULTS: A total of 191 patients underwent stent placement. The 30-day readmission rate was 17.3 % (N = 33). Readmissions were for stent-related complications in 7.3 % (N = 14) and non-stent-related complications in 9.9 % (N = 19). Stent placement was technically successful in 185 of 191 (96.9 %) and clinically successful in 170 of 191 (89.0 %) patients. On long-term follow-up, 32 (16.8 %) patients needed re-intervention. The mean stent patency was 142 days. Readmission within 30 days was independently associated with development of early complications (<7 days) following stent placement (odds ratio [OR] 5.90; 95 % confidence interval [CI] 2.04­17.1), while the stent location did not impact readmission risk. On Cox regression analysis, American Society of Anesthesiologists physical classification (OR 1.36; 95 % CI 1.02­1.87) and stent location in the esophagus (OR 1.82; 95 % CI 1.10­3.02) were independently associated with long-term mortality. CONCLUSIONS: Early complications following stent placement increase the risk of 30-day readmission. SEMS is efficacious long-term for palliation of malignant gastrointestinal obstruction.

Fluorescence in situ hybridization for diagnosis of cholangiocarcinoma in primary sclerosing cholangitis: a systematic review and meta-analysis.

BACKGROUND: Patients with primary sclerosing cholangitis (PSC) are at risk of developing cholangiocarcinoma (CCA). Fluorescence in situ hybridization (FISH) may aid diagnosis of CCA. OBJECTIVE: To determine the diagnostic utility of FISH for CCA detection in patients with PSC. DESIGN: Meta-analysis. SETTING: Tertiary-care medical center. PATIENTS: Patients in studies where histopathologic correlation of CCA was available; 2 × 2 contingency data were constructed. INTERVENTION: Database search and review of study findings. MAIN OUTCOME MEASUREMENTS: Sensitivity, specificity, likelihood ratio, and pooled diagnostic odds ratio. RESULTS: The search yielded 8 studies, involving 828 patients who could be included in our meta-analysis. The pooled sensitivity and specificity of FISH for diagnosis of CCA in patients with PSC were 68% (95% confidence interval [CI], 61%-74%) and 70% (95% CI, 66%-73%), respectively. The pooled positive likelihood ratio was 2.69 (95% CI, 1.84-3.97), and the negative likelihood ratio was 0.47 (95% CI, 0.39-0.58). The pooled diagnostic odds ratio was 7.24 (95% CI, 3.93-13.36). For FISH polysomy (6 studies, n = 690), the pooled sensitivity and specificity of FISH were 51% (95% CI, 43%-59%) and 93% (95% CI, 91%-95%), respectively. The heterogeneity indices of I(2) measure of inconsistency was 45.9%. Visual inspection of the funnel plot showed low potential for publication bias. LIMITATIONS: Inclusion of low-quality studies. CONCLUSION: Our study suggests that FISH polysomy is highly specific; however, limited sensitivity of FISH highlights that better markers are required for early detection of CCA in PSC.

Progression of low-grade dysplasia to advanced neoplasia based on the location and morphology of dysplasia in ulcerative colitis patients with extensive colitis under colonoscopic surveillance.

BACKGROUND: The management of low-grade dysplasia (LGD) in ulcerative colitis (UC) patients remains unclear. AIM: The aim of our study was to study the risk of progression of LGD to advanced neoplasia (AN), defined as high-grade dysplasia (HGD) or colorectal cancer (CRC) for UC patients undergoing surveillance based on location and morphology of LGD. METHODS: 997 UC patients underwent 3152 surveillance colonoscopies from 1998 to 2011. Kaplan-Meier estimates and incidence rates calculated. RESULTS: Of the 102 patients with LGD (65 raised and 37 flat), 5 (4.9%) patients progressed to AN (3 HGD and 2 CRC) after a median follow-up of 36 months (interquartile range 18-71 months). Initial location of dysplasia was in the proximal colon in 47, distal colon in 55 patients. Four of the 5 (80%) patients with AN had initial dysplasia in the distal colon. Distal colonic LGD had an incidence rate for AN of 2.1 cases per 100 person years at risk, while proximal LGD had an incidence of 0.5 cases per 100 person years. Flat LGD in the distal colon was more likely to progress to AN [hazard ratio=3.6; 95% confidence interval, CI (1.3-10.6)]. Twenty of the 102 patients (15 flat and 5 raised) underwent colectomy: 2 (10%) had evidence of AN in colectomy (1 HGD and 1 CRC), 9 had LGD and remaining 9 did not have dysplasia. CONCLUSIONS: The frequency of progression of LGD to AN is low. Flat dysplasia located in the distal colon is associated with a greater risk of progression to AN.

Vascular endothelial growth factor levels in bile distinguishes pancreatic cancer from other etiologies of biliary stricture: a pilot study.

BACKGROUND: Determining the benign or malignant nature of biliary strictures can be challenging. Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis. OBJECTIVE: The purpose of this study was to investigate whether VEGF levels in bile aspirated during endoscopic retrograde cholangiography (ERCP) can distinguish pancreatic cancer from other causes of biliary stricture. METHODS: Bile was directly aspirated in 53 consecutive patients from March 2012 to October 2012 during ERCP from the common bile duct including 15 with pancreatic cancer, 18 with primary sclerosing cholangitis (PSC), nine with cholangiocarcinoma (CCA), and 11 with benign biliary conditions (sphincter of Oddi and choledocholihiasis). Levels of VEGF in bile were measured. The diagnostic performance was then validated in a second, independent validation cohort of 18 patients (pancreatic cancer n = 10, benign n = 8). RESULTS: A total of 53 consecutive patients were recruited. The median bile VEGF levels were significantly elevated in patients with pancreatic cancer (1.9 ng/ml (interquartile range [IQR] 0.7, 2.2) compared to those with benign biliary conditions (0.3 ng/ml [IQR 0.2, 0.6]; p < 0.001), PSC (0.7 ng/ml [IQR 0.5, 0.9]; p = 0.02) or CCA (0.4 ng/ml [IQR 0.1, 0.5]; p < 0.001). A VEGF cut-off value of 0.5 ng/ml distinguished pancreatic cancer from CCA with a sensitivity and specificity of 93.3 and 88.9 %, respectively, and area under curve (AUC) of 0.93, and from benign conditions with a sensitivity and specificity of 93.3 and 72.7 %, respectively, with AUC of 0.89. The diagnostic accuracy of biliary VEGF was confirmed in the second independent validation cohort. CONCLUSIONS: This study suggests that measurement of biliary VEGF-1 levels distinguishes patients with pancreatic cancer from other etiologies of biliary stricture. This may be particularly relevant in approaching patients with indeterminate biliary stricture.

Delay in performing ERCP and adverse events increase the 30-day readmission risk in patients with acute cholangitis.

BACKGROUND: Readmission to the hospital within 30 days of discharge (30-day readmission rate) is used as a quality measure. OBJECTIVE: To investigate the incidence and factors that contribute to readmissions in patients with acute cholangitis. DESIGN: Retrospective cohort study. SETTING: Tertiary-care referral center. PATIENTS: Retrospective analysis of consecutive patients admitted to our center for acute cholangitis and ERCP. INTERVENTION ERCP MAIN OUTCOME MEASUREMENTS: Incidence and variables associated with 30-day readmission and 1-year mortality. RESULTS: ERCP was successful in 98.8% of patients during the index admission. The 30-day readmission rate was 22.0%. Recurrence of cholangitis was the most common etiology for readmissions (37.8%). Readmission within 30 days was independently associated with failed ERCP or ERCP delayed for >48 hours (odds ratio [OR] 2.47; 95% confidence interval [CI], 1.01-6.07), development of any after-ERCP adverse event (OR 11.0; 95% CI, 3.06-39.30), and the etiology of cholangitis (etiologies not related to stones) (OR 3.3; 95% CI, 1.17-9.18). Every 1-point increase in the Charlson Comorbidity Index score (OR, 1.33; 95% CI, 1.05-1.69) was associated significantly with 1-year mortality. In unadjusted analysis, 30-day readmission after ERCP was associated significantly with 1-year mortality (OR, 2.86; 95% CI, 1.16-7.07). This association, however, was not present after adjustment for other covariates. LIMITATIONS: Retrospective study. CONCLUSION: Delays in performing ERCP during the index admission, development of after-ERCP adverse events, and etiology of cholangitis not related to stones increased the risk of 30-day readmissions.

Random biopsies during surveillance colonoscopy increase dysplasia detection in patients with primary sclerosing cholangitis and ulcerative colitis.

BACKGROUND AND AIM: Patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) are at increased risk of colon dysplasia. The role of random vs. target biopsies in these patients has not been investigated. Our aim was to evaluate the yield and clinical impact of random biopsies during surveillance colonoscopies in patients with PSC-UC. METHODS: Data from 71 patients (267 colonoscopies) with PSC and UC, who underwent surveillance colonoscopies and followed-up from 2001 to 2011 was obtained. Colonoscopy and pathology reports were reviewed to assess the yield of random biopsies. RESULTS: A total of 3975 (median 12) random biopsies were taken during surveillance colonoscopies. Overall, neoplasia was detected in 22 colonoscopies (16 patients): in 8 colonoscopies (36.4%) by targeted biopsies only and in 4 (18.2%) by both targeted and random biopsies. Neoplasia was detected in random biopsies only in 10 (45.5%) colonoscopies in 8 patients. On multivariate analysis, duration of UC (Odds ratio [OR]=1.40; 95% confidence interval [CI], 1.08-1.81; P=0.01), number of random biopsies (per increase by 8) (OR=1.64; 95% CI, 1.18-2.28; P=0.003) and target biopsies during colonoscopy (OR=9.08; 95% CI, 3.18-26.0; P<0.001) independently predicted the presence of dysplasia; endoscopic features of prior inflammation did not. CONCLUSIONS: Random biopsies significantly increase the yield of dysplasia in patients with PSC and UC even in the absence of endoscopic features of prior inflammation and significantly impact clinical outcomes.

Backwash ileitis and the risk of colon neoplasia in ulcerative colitis patients undergoing restorative proctocolectomy.

BACKGROUND: The significance of backwash ileitis (BWI) relating to the risk of colon neoplasia in ulcerative colitis (UC) patients is controversial. AIM: We investigated the association between BWI and the presence of colon neoplasia in the colectomy specimen. METHODS: From 4,198 UC patients in a prospectively maintained pouch database from 1983 to 2011, patients with extensive colitis and BWI (n = 178) in proctocolectomy were compared with 537 controls [extensive colitis (n = 385) and left-sided colitis (n = 152)] without ileal inflammation. RESULTS: Colon neoplasia (colon dysplasia and/or colon cancer) was seen in 32 (18 %) patients with BWI in contrast to 45 (11.7 %) with extensive colitis and 13 (8.6 %) with left-sided colitis alone (p = 0.03). Of those with BWI, colon cancer was seen in 10 patients (5.6 %), while low grade and high grade dysplasia were seen in 7 (3.9 %) and 15 (8.4 %) patients respectively. On multivariate analysis, the presence of BWI with extensive colitis [odds ratio (OR) = 3.53; 95 % confidence interval (CI) 1.01-12.30, p = 0.04], presence of primary sclerosing cholangitis (PSC) (OR = 5.79, 95 % CI 1.92-17.40, p = 0.002) and moderate to severe disease activity at UC diagnosis (OR 4.29, 95 % CI 2.06-9.01, p < 0.001) were associated with an increased risk for identifying any colon neoplasia. For colon cancer, the presence of PSC (OR = 11.30, 95 % CI 1.54-80.9, p = 0.01) was the only factor independently associated with an increased risk. CONCLUSIONS: The presence of BWI with extensive colitis was associated with the risk of identifying colon neoplasia but not cancer alone in the proctocolectomy specimen.

Natural history of low grade dysplasia in patients with primary sclerosing cholangitis and ulcerative colitis.

BACKGROUND AND AIM: Patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC) are at increased risk of colon cancer. The aim of this study was to determine the natural history of LGD and its progression to high grade dysplasia (HGD)/colorectal cancer (CRC) in PSC-UC patients. METHODS: Ten PSC-UC patients with LGD who underwent surveillance colonoscopy from 1996 to 2011 were evaluated. Raised dysplasia was defined as a discrete raised lesion located in an area involved by either quiescent or active colitis that was endoscopically resected, while flat dysplasia was defined as the absence of documentation of a raised lesion. RESULTS: Of the 10 patients with LGD, 3 (30%) progressed to raised HGD over a mean follow-up of 13±11 months. Three of 10 patients had initial raised LGD while 7 had flat LGD. The location of HGD was in the proximal colon in all 3 patients. However all 3 patients who progressed to HGD had initial dysplasia located in the distal colon and had flat morphology. The incidence rate for detection of HGD/CRC was 9.4 cases per 100 person years at risk. Patients with LGD with flat morphology had an incidence rate of 17.8 cases per 100 person years at risk. HGD occurred more frequently within the first year of initial detection of LGD (23.5 per 100 patient years of follow-up). CONCLUSIONS: One-third of patients with LGD progressed to HGD/CRC in PSC-UC. Most patients progress within the first year of diagnosis of LGD supporting early colectomy in PSC-UC patients with LGD.

End-stage renal disease is associated with worse outcomes in hospitalized patients with peptic ulcer bleeding.

BACKGROUND: Patients with end-stage renal disease (ESRD) are at increased risk of peptic ulcer bleeding (PUB). To our knowledge, there are no population-based studies of the impact of ESRD on PUB. OBJECTIVE: To determine nationwide impact of ESRD on outcomes of hospitalized patients with PUB. DESIGN: Cross-sectional study. SETTING: Hospitals from a 2008 Nationwide Inpatient Sample. PATIENTS: We used the International Classification of Diseases, the 9th Revision, Clinical Modification codes to identify patients who had a primary discharge diagnosis of PUB. MAIN OUTCOME MEASUREMENT: In-hospital mortality, length of stay, and hospitalization charges. INTERVENTIONS: Comparison of PUB outcomes in patients with and without ESRD. RESULTS: Of a total of 102,525 discharged patients with PUB, 3272 had a diagnosis of both PUB and ESRD, whereas 99,253 had a diagnosis of PUB alone without ESRD. The mortality of ESRD patients with PUB was significantly higher than that of the control group without ESRD (4.8% vs 1.9%, P < .0001). On multivariate analysis, patients with PUB and ESRD had greater mortality than patients admitted to the hospital with PUB alone (adjusted odds ratio [aOR] 2.1; 95% confidence interval [CI], 1.3-3.4), were more likely to undergo surgery (aOR 1.4; 95% CI, 1.2-1.7), and had a longer hospital stay (aOR 2.1; 95% CI, 1.2-2.9). These patients also incurred higher hospitalization charges ($54,668 vs $32,869, P < .01) compared with patients with PUB alone. LIMITATIONS: Administrative data set. CONCLUSIONS: ESRD is associated with a significant health care burden in hospitalized patients with PUB. The presence of ESRD contributes to a higher mortality rate, longer hospital stay, and increased need for surgery.

Increased serum levels of carbohydrate antigen 19-9 and outcomes in primary sclerosing cholangitis patients without cholangiocarcinoma.

BACKGROUND: Carbohydrate antigen 19-9 (CA 19-9) is the serum marker used to diagnose cholangiocarcinoma (CCA) in patients with primary sclerosing cholangitis (PSC). AIM: We investigated long-term outcomes in patients with PSC and elevated CA 19-9 levels without CCA. METHODS: A total of 166 PSC patients with serum levels of CA 19-9 without CCA followed at a single center from 1998 to 2011 were included. Patients with and without elevated CA 19-9 levels (greater than 129 U/ml) were compared. RESULTS: Fifty-two (31.3 %) of the 166 patients with PSC without CCA had elevated serum CA-19-9. Patients with elevated CA-19-9 were followed for a mean of 4 years and 12 (23.1 %) died. They were more likely to have higher PSC risk score (1.67 ± 1.30 vs. 0.91 ± 1.53, p = 0.003) and dominant strictures (31 (59.6 %) vs. 21 (18.4 %), p < 0.001). In 17/52 (32.7 %) of patients with elevated CA-19-9, no etiology was identified; cholestasis and cholangitis were associated with elevated levels in 24/52 (48.1 %) and 11/52 (21.2 %), respectively. There were 32 of 52 (62.5 %) that underwent orthotopic liver transplantation (OLT) in elevated CA 19-9 group compared to 66/114 (56.9 %) without (p = 0.66). The median OLT-free survival with elevated CA 19-9 was 9 years from PSC diagnosis compared to 14 years without. Although there was a trend, there was no significant difference in the OLT-free survival on Kaplan-Meier analysis (log rank p = 0.12). CONCLUSIONS: Thirty-two percent of patients with PSC had elevated serum CA 19-9 in the absence of CCA. There was a trend towards shorter OLT-free survival in PSC patients with elevated CA-19-9.

Elevated immunoglobulin G4 level is associated with reduced colectomy-free survival in patients with primary sclerosing cholangitis and ulcerative colitis.

BACKGROUND AND AIM: Patients with primary sclerosing cholangitis (PSC) and elevated immunoglobulin (Ig) G4 have been shown to have more severe disease with a shorter time to orthotopic liver transplantation (OLT). The aim of the study was to investigate the clinical outcomes of PSC and UC in patients with elevated serum IgG4. METHODS: We analyzed data from 50 patients with PSC and known serum levels of IgG4. They were divided into groups called high IgG4 (>112 IU/L; n = 10) or normal IgG4 (n = 40). We compared the requirement of OLT and colectomy between groups. RESULTS: High IgG4 was found in 10 PSC patients (20%). UC was associated in 9/10 patients with high IgG4 vs. 32/40 patients with normal IgG4 (p=0.67). Patients with high IgG4 were younger at PSC diagnosis (28.1 ± 13.9 vs. 37.6 ± 13.4 years, P=0.04), more likely to have backwash ileitis (7/9 vs. 12/32, P < 0.001) and UC flares (median of 5.5 vs. 1.5, P = 0.02). Kaplan-Meier curve analysis showed that patients with elevated IgG4 had reduced colectomy-free survival than patients with normal IgG4 (Log Rank p < 0.001). The median time to colectomy was 5 years from UC diagnosis in high IgG4 group vs. 12 years in the normal IgG4 group (p = 0.01). CONCLUSIONS: Elevated IgG4 was seen in a small number of PSC patients. Most of these patients had associated UC, were younger at the time of PSC diagnosis, more likely to have backwash ileitis and had reduced colectomy-free survival than patients with normal IgG4.

Impact of inflammatory bowel disease on post-cholecystectomy complications and hospitalization costs: a Nationwide Inpatient Sample study.

BACKGROUND AND AIM: Our previous single-center study showed that patients with underlying inflammatory bowel disease (IBD) had a higher risk for post-cholecystectomy complications. The aim of the current population-based study was to verify whether concomitant IBD was indeed associated with an increased risk of post-cholecystectomy complications. METHODS: In this cross-sectional study, all 1,155,432 patients from the Nationwide Inpatient Sample (NIS) with a primary procedure of cholecystectomy were examined, and 5891 patients with IBD were compared with 1,149,541 patients without IBD from 2006 to 2008. RESULTS: There were no significant differences in age, gender, frequency of obesity, and post-operative mortality between the two groups. More patients in the IBD group had post-operative complications than the non-IBD group [398/5891 (6.8%) vs. 55,202/1,149,541 (4.8%), p=0.002)]. On multivariate analysis, the presence of Crohn's disease (CD) was associated with an increased risk for post-operative complications (odds ratio [OR]=1.6; 95% confidence interval [CI], 1.2-2.1, p=0.003). The other risk factors for post-cholecystectomy complications were older age, male gender, African-American race, malnutrition and patients with higher co-morbidity index. The presence of ulcerative colitis (UC) was associated with a trend for increased complications (OR=1.3, 95% CI 0.8-2.1, p=0.08). Patients with IBD who underwent cholecystectomy incurred higher mean hospital costs ($39,651 vs. $35,196, p=0.006) and also stayed in the hospital 1.2 days longer than those without underlying IBD. CONCLUSIONS: CD patients undergoing cholecystectomy were shown to have a significantly increased risk for postoperative complications, have a longer stay in the hospital, and incur higher hospitalization costs.

Diagnosis and therapeutic management of extra-intestinal manifestations of inflammatory bowel disease.

Extra-intestinal manifestations (EIMs) are reported frequently in patients with inflammatory bowel disease (IBD) and may be diagnosed before, concurrently or after the diagnosis of IBD. EIMs in IBD may be classified based on their association with IBD disease activity. The first group has a direct relationship with the activity of the bowel disease and includes pauciarticular arthritis, oral aphthous ulcers, erythema nodosum and episcleritis. The second group of EIMs appears to follow an independent course from the underlying bowel disease activity and include ankylosing spondylitis and uveitis. The third group includes EIMs that may or may not be related to intestinal inflammation, such as pyoderma gangrenosum and probably primary sclerosing cholangitis (PSC). Genetic susceptibility, aberrant self-recognition and immunopathogenic autoantibodies against organ-specific cellular antigens shared by the colon and extra-colonic organs may contribute to the pathogenesis and development of these EIMs. The use of biological agents in the IBD armamentarium has expanded the treatment options for some of the disabling EIMs and these agents form the cornerstone in managing most of the disabling EIMs. PSC is one of the most common hepatobiliary manifestations associated with IBD in which no clear treatment options exist other than endoscopic therapy and liver transplantation. Future research targeting the pathogenesis, early diagnosis and treatment of these EIMs is required.