Projected Colorectal Cancer Incidence and Mortality Based on Observed Adherence to Colonoscopy and Sequential Stool-Based Screening.

INTRODUCTION: Modeling supporting recommendations for colonoscopy and stool-based colorectal cancer (CRC) screening tests assumes 100% sequential participant adherence. The impact of observed adherence on the long-term effectiveness of screening is unknown. We evaluated the effectiveness of a program of screening colonoscopy every 10 years vs annual high-sensitivity guaiac-based fecal occult blood testing (HSgFOBT) using observed sequential adherence data. METHODS: The MIcrosimulation SCreening ANalysis (MISCAN) model used observed sequential screening adherence, HSgFOBT positivity, and diagnostic colonoscopy adherence in HSgFOBT-positive individuals from the National Colonoscopy Study (single-screening colonoscopy vs ≥4 HSgFOBT sequential rounds). We compared CRC incidence and mortality over 15 years with no screening or 10 yearly screening colonoscopy vs annual HSgFOBT with 100% and differential observed adherence from the trial. RESULTS: Without screening, simulated incidence and mortality over 15 years were 20.9 (95% probability interval 15.8-26.9) and 6.9 (5.0-9.2) per 1,000 participants, respectively. In the case of 100% adherence, only screening colonoscopy was predicted to result in lower incidence; however, both tests lowered simulated mortality to a similar level (2.1 [1.6-2.9] for screening colonoscopy and 2.5 [1.8-3.4] for HSgFOBT). Observed adherence for screening colonoscopy (83.6%) was higher than observed sequential HSgFOBT adherence (73.1% first round; 49.1% by round 4), resulting in lower simulated incidence and mortality for screening colonoscopy (14.4 [10.8-18.5] and 2.9 [2.1-3.9], respectively) than HSgFOBT (20.8 [15.8-28.1] and 3.9 [2.9-5.4], respectively), despite a 91% adherence to diagnostic colonoscopy with FOBT positivity. The relative risk of CRC mortality for screening colonoscopy vs HSgFOBT was 0.75 (95% probability interval 0.68-0.80). Findings were similar in sensitivity analyses with alternative assumptions for repeat colonoscopy, test performance, risk, age, and projection horizon. DISCUSSION: Where sequential adherence to stool-based screening is suboptimal and colonoscopy is accessible and acceptable-as observed in the national colonoscopy study, microsimulation, comparative effectiveness, screening recommendations.

Randomized Trial of Facilitated Adherence to Screening Colonoscopy vs Sequential Fecal-Based Blood Test.

BACKGROUND & AIMS: Colorectal cancer (CRC) screening guidelines include screening colonoscopy and sequential high-sensitivity fecal occult blood testing (HSgFOBT), with expectation of similar effectiveness based on the assumption of similar high adherence. However, adherence to screening colonoscopy compared with sequential HSgFOBT has not been reported. In this randomized clinical trial, we assessed adherence and pathology findings for a single screening colonoscopy vs sequential and nonsequential HSgFOBTs. METHODS: Participants aged 40-69 years were enrolled at 3 centers representing different clinical settings. Participants were randomized into a single screening colonoscopy arm vs sequential HSgFOBT arm composed of 4-7 rounds. Initial adherence to screening colonoscopy and sequential adherence to HSgFOBT, follow-up colonoscopy for positive HSgFOBT tests, crossover to colonoscopy, and detection of advanced neoplasia or large serrated lesions (ADN-SERs) were measured. RESULTS: There were 3523 participants included in the trial; 1761 and 1762 participants were randomized to the screening colonoscopy and HSgFOBT arms, respectively. Adherence was 1473 (83.6%) for the screening colonoscopy arm vs 1288 (73.1%) for the HSgFOBT arm after 1 round (relative risk [RR], 1.14; 95% CI, 1.10-1.19; P ≤ .001), but only 674 (38.3%) over 4 sequential HSgFOBT rounds (RR, 2.19; 95% CI, 2.05-2.33). Overall adherence to any screening increased to 1558 (88.5%) in the screening colonoscopy arm during the entire study period and 1493 (84.7%) in the HSgFOBT arm (RR, 1.04; 95% CI, 1.02-1.07). Four hundred thirty-six participants (24.7%) crossed over to screening colonoscopy during the first 4 rounds. ADN-SERs were detected in 121 of the 1473 participants (8.2%) in the colonoscopy arm who were adherent to protocol in the first 12 months of the study, whereas detection of ADN-SERs among those who were not sequentially adherent (n = 709) to HSgFOBT was subpar (0.6%) (RR, 14.72; 95% CI, 5.46-39.67) compared with those who were sequentially adherent (3.3%) (n = 647) (RR, 2.52; 95% CI, 1.61-3.98) to HSgFOBT in the first 4 rounds. When including colonoscopies from HSgFOBT patients who were never positive yet crossed over (n = 1483), 5.5% of ADN-SERs were detected (RR, 1.50; 95% CI, 1.15-1.96) in the first 4 rounds. CONCLUSIONS: Observed adherence to sequential rounds of HSgFOBT was suboptimal compared with a single screening colonoscopy. Detection of ADN-SERs was inferior when nonsequential HSgFOBT adherence was compared with sequential adherence. However, the greatest number of ADN-SERs was detected among those who crossed over to colonoscopy and opted to receive a colonoscopy. The effectiveness of an HSgFOBT screening program may be enhanced if crossover to screening colonoscopy is permitted. CLINICALTRIALS: gov, Number: NCT00102011.

The Aftermath of a Hepatic Artery Aneurysm-A Rare Etiology of Biliary Obstruction!

BACKGROUND: Hepatic artery aneurysms (HAAs) constitute 14% to 20% of visceral artery aneurysms. Most HAAs are asymptomatic. Although rare, obstructive jaundice due to external bile duct compression or rupture of the HAA into the biliary tree with occlusion of the lumen from blood clots has been reported. CASE PRESENTATION: A 56-year-old white man presented to an outside hospital with symptoms of obstructive jaundice, including abdominal pain and yellowing of the skin. Imaging showed a large HAA. Patient was transferred to our hospital where an endoscopic retrograde cholangiopancreatography with biliary stenting was performed. This was followed by coil embolization of the HAA with improvement in symptoms and liver chemistries. CONCLUSIONS: Most clinicians agree that management of HAA is highly variable and depends on clinical presentation and anatomic location. Biliary stenting provides temporary relief for patients with obstructive jaundice. Definitive options include open aneurysmal repair versus endovascular therapy. Hepatic artery aneurysms represent a significant risk for hemorrhage and therefore must be addressed promptly once discovered.

Development and validation of a clinical score for predicting risk of adenoma at screening colonoscopy.

BACKGROUND: Currently, no clinical tools use demographic and risk factor information to predict the risk of finding an adenoma in individuals undergoing colon cancer screening. Such a tool would be valuable for identifying those who would most benefit from screening colonoscopy. METHODS: We used baseline data from men and women who underwent screening colonoscopy from the randomized, multicenter National Colonoscopy Study (NCS) to develop and validate an adenoma risk model. The study, conducted at three sites in the United States (Minneapolis, MN; Seattle, WA; and Shreveport, LA) asked all participants to complete baseline questionnaires on clinical risk factors and family history. Model parameters estimated from logistic regression yielded an area under the receiver operating characteristic curve (AUROCC) used to assess prediction. RESULTS: Five hundred forty-one subjects were included in the development model, and 1,334 in the validation of the risk score. Variables in the prediction of adenoma risk for colonoscopy screening were age (likelihood ratio test for overall contribution to model, P < 0.001), male sex (P < 0.001), body mass index (P < 0.001), family history of at least one first-degree relative with colorectal cancer (P = 0.036), and smoking history (P < 0.001). The adjusted AUROCC of 0.67 [95% confidence interval (CI), 0.61-0.74] for the derivation cohort was not statistically significantly different from that in the validation cohort. The adjusted AUROCC for the entire cohort was 0.64 (95% CI, 0.60-0.67). CONCLUSION: We developed and validated a simple well-calibrated risk score. IMPACT: This tool may be useful for estimating risk of adenomas in screening eligible men and women.

Diabetic Ketoacidosis-induced Hypertriglyceridemic Acute Pancreatitis Treated with Plasmapheresis-Recipe for Biochemical Disaster Management.

Diabetic ketoacidosis (DKA)-induced hypertriglyceridemia causing pancreatitis is an interesting phenomenon that has rarely been reported in literature. Plasmapharesis is a well known treatment modality for hypertriglyceridemia-induced pancreatitis. We report a patient with DKA-induced hypertriglyceridemic acute pancreatitis treated successfully with plasmapharesis.

African-American inflammatory bowel disease in a Southern U.S. health center.

BACKGROUND: Inflammatory Bowel Diseases (IBD) remain significant health problems in the US and worldwide. IBD is most often associated with eastern European ancestry, and is less frequently reported in other populations of African origin e.g. African Americans ('AAs'). Whether AAs represent an important population with IBD in the US remains unclear since few studies have investigated IBD in communities with a majority representation of AA patients. The Louisiana State University Health Sciences Center in Shreveport (LSUHSC-S) is a tertiary care medical center, with a patient base composed of 58% AA and 39% Caucasian (W), ideal for evaluating racial (AA vs. W) as well and gender (M vs. F) influences on IBD. METHODS: In this retrospective study, we evaluated 951 visits to LSUHSC-S for IBD (between 2000 to 2008) using non-identified patient information based on ICD-9 medical record coding (Crohn's disease 'CD'-555.0- 555.9 and ulcerative colitis 'UC'-556.0-556.9). RESULTS: Overall, there were more cases of CD seen than UC. UC and CD affected similar ratios of AA and Caucasian males (M) and females (F) with a rank order of WF > WM > AAF > AAM. Interestingly, in CD, we found that annual visits per person was the highest in AA M (10.7 ± 1.7); significantly higher (* -p < 0.05) than in WM (6.3 ± 1.0). Further, in CD, the female to male (F: M) ratio in AA was significantly higher (*- p < 0.05) (1.9 ± 0.2) than in Caucasians (F:M = 1.3 ± 0.1) suggesting a female dominance in AACD; no differences were seen in UC F: M ratios. CONCLUSION: Although Caucasians still represent the greatest fraction of IBD (~64%), AAs with IBD made up >1/3 (36.4%) of annual IBD cases from 2000-2008 at LSUHSC-S. Further studies on genetic and environments risks for IBD risk in AAs are needed to understand differences in presentation and progression in AAs and other 'non-traditional' populations.

Inflammatory cytokines induce MAdCAM-1 in murine hepatic endothelial cells and mediate alpha-4 beta-7 integrin dependent lymphocyte endothelial adhesion in vitro.

BACKGROUND: MAdCAM-1 plays a central role in T-lymphocyte homing to the gut, but its role in chronic liver inflammation remains unknown. Therefore, this study measured MAdCAM-1 expression, regulation, and function in cultured murine hepatic endothelial cells. METHODS: Cultures of hepatic endothelial cells (HEC) were prepared from mice expressing a temperature-sensitive SV40 large T antigen (H-2Kb-tsA58) under the control of an IFN-gamma promoter. Time and dose dependent expression of MAdCAM-1 in response to TNF-alpha, IL-1 beta and IFN-gamma was studied by immunoblotting. Lymphocyte adhesion was studied using alpha 4 beta 7 integrin expressing lymphocytes (TK-1) +/- anti-MAdCAM-1 mAb. RESULTS: TNF-alpha induced MAdCAM-1 dose-and time-dependently with maximum expression at 20 ng/ml and at 48 hours. IL-1 beta also induced MAdCAM-1 to a lesser extent compared to TNF-alpha; IFN-gamma did not induce MAdCAM-1. TNF-alpha significantly increased lymphocyte-endothelial adhesion (P < 0.01), which was reversed by anti-MAdCAM-1 antibody. MAdCAM-1 expression was also reduced by N-acetylcysteine and by two NO donors (SperNO, DETANO) suggesting that hepatic endothelial MAdCAM-1 is oxidant and NO regulated. CONCLUSION: MAdCAM-1 is a major determinant of leukocyte recruitment in chronic inflammation and is expressed by HEC in response to IL-1 beta and TNF-alpha. This system may provide a useful model for studying inflammatory mechanisms in liver disease and help determine if controlled MAdCAM-1 expression might influence inflammation in liver disease.

Eosinophilic gastroenteritis of the pancreas: an unusual cause of obstructive jaundice.

Eosinophilic gastroenteritis (EG) is a rare gastrointestinal disorder of undetermined etiology and is manifest by eosinophilic infiltration of any area of gastrointestinal tract, most frequently stomach and small intestine. Peripheral eosinophilia is present in about 80% of patients. Definitive diagnosis requires histologic evidence of eosinophilic infiltration; which is usually patchy in distribution. Steroids are the mainstay of treatment. We present a case of 47-year-old man with abdominal pain, jaundice, and marked eosinophilia. Endoscopic retrograde cholangio-pancreatogram revealed a dilated common bile duct. There was biopsy proven eosinophilic infiltration in stomach, duodenum, gall bladder, and pancreas. Obstructive jaundice is an extremely rare manifestation of EG. This unusual case illustrates the wide variety of gastrointestinal manifestations caused by EG and emphasizes the importance of clinical suspicion and endoscopic mucosal biopsies in diagnosis of EG. This entity should be considered in the patients with chronic and relapsing gastrointestinal symptoms.

Spontaneous pneumomediastinum due to achalasia: a case report.

Spontaneous pneumomediastinum (SPM) is a rare and benign clinical entity characterized by free air around mediastinal structures. Precipitating factors include violent cough, asthma, inhalational drugs, labor and exercise. We report a case of SPM due to achalasia which to the best of our knowledge, has never been reported. In achalasia, Valsalva maneuver might accompany severe vomiting. This causes alveolar rupture due to elevated intrabronchial and intra-alveolar pressure. Air tracks along the mediastinal spaces cause SPM. In our patient, there was no evidence of esophageal perforation. Tension pneumomediastinum and pneumothorax are complications of SPM.