Animal Models of Barrett's Esophagus and Esophageal Adenocarcinoma–Past,Present, and Future

Esophageal adenocarcinoma is the fastest rising cancer in the United States. It develops from long‐standing gastroesophageal reflux disease which affects >20% of the general population. It carries a very poor prognosis with 5‐year survival <20%. The disease is known to sequentially progress from reflux esophagitis to a metaplastic precursor, Barrett''s esophagus and then onto dysplasia and esophageal adenocarcinoma. However, only few patients with reflux develop Barrett''s esophagus and only a minority of these turn malignant. The reason for this heterogeneity in clinical progression is unknown. To improve patient management, molecular changes which facilitate disease progression must be identified. Animal models can provide a comprehensive functional and anatomic platform for such a study. Rats and mice have been the most widely studied but disease homology with humans has been questioned. No animal model naturally simulates the inflammation to adenocarcinoma progression as in humans, with all models requiring surgical bypass or destruction of existing antireflux mechanisms. Valuable properties of individual models could be utilized to holistically evaluate disease progression. In this review paper, we critically examined the current animal models of Barrett''s esophagus, their differences and homologies with human disease and how they have shaped our current understanding of Barrett''s carcinogenesis.     

Alcohol consumption patterns and predictors of use following liver transplantation for alcoholic liver disease.

For patients who receive a liver transplant (LTX) for alcoholic liver disease (ALD), investigators are focusing beyond survival to determine specific alcohol use outcomes. Studies suggest the use of alcohol ranges from 8 to 22% for the first post-transplant year with cumulative rates reaching 30 to 40% by 5 years following transplantation. Yet while investigators are interested in determining specific rates of alcohol use and predictors of use, only three studies since 1990 have been prospective. In 1998, we began a prospective study of post-LTX alcohol consumption in ALD recipients using multiple repeated measures of alcohol use. After 5 years of follow-up, we found that 22% had used any alcohol by the first year and 42% had a drink by 5 years. By 5 years, 26% drank at a heavier use (binge) pattern and 20% drank in a frequent pattern. In a univariate model, predictors of alcohol use included pre-transplant length of sobriety, a diagnosis of alcohol dependence, a history of other substance use, and prior alcohol rehabilitation.     

Predictors of long-term survival in patients with gallbladder cancer

The aim of this study was to examine the predictors of long-term survival (>24 months) in patients with gall bladder cancer. A retrospective review of 117 cases of gall bladder cancer resected between 1989 and 2000. The resections included 80 simple cholecystectomies and 37 extended procedures. Patients with survival >24 months (n=44) were compared with those having survival <24 months (n=73) for 17 prognostic factors. Overall median survival was 16 months with a 5-year survival of 27%. T status (P=.000) and adjuvant chemoradiotherapy (P=.001) were independent predictors of long-term survival. Survival advantage was seen in T3N+ve disease (P=.007) with extended procedures. Complete (R0) resection was attained in 30 patients with a 5-year survival advantage of 30% as compared with incomplete (R1) resection (P=.0002). Adjuvant chemoradiotherapy improved survival in simple cholecystectomy group (P=.0008) but no advantage was seen after extended procedures. Stage III (P=.001) and node-positive disease (P=.0005) had significant benefit with adjuvant therapy. Poor differentiation and vascular invasion were associated with poor long-term survival. R0 resection was associated with prolonged survival. Extended procedures improved survival in patients with T3N+ve disease. Addition of chemoradiotherapy made significant improvement in long-term survival in stage III and node-positive lesions and in patients undergoing simple cholecystectomy. R0 resection predicted long-term survival in gall bladder cancer. T3 N+ve disease had better survival after extended procedures. Adjuvant chemoradiotherapy improved survival in stage III and node-positive disease. Poor differentiation and vascular invasion were adverse predictors of survival.     

Pediatric valve replacement, 15 years experience in Oman

Background Despite improving surgical techniques, treatment of heart valve disease in children remains controversial. Somatic growth and adequate anticoagulation are of concern when children undergo valve replacement. We conducted this study to evaluate the performance of valves in this age group. Methods 42 children under the age of 13 years who underwent valve replacement were included in this study. Totally, 50 valves were implanted in 42 patients: 48 were mechanical prostheses, two were bioprosthetic both in pulmonary position. 37 (74%) valves were implanted in mitral position, 10 (20%) in aortic position, 1 (2%) in tricuspid position and 2 (4%) in pulmonary position. Preoperatively, 14 (33,3%) patients were in New York Heart Association (NYHA) class IV, while 27 (64.2%) were in NYHA class III. Results There were 2 (4.7%) hospital deaths and 2 (4.7%) late deaths while 2 (4.7%) patients were lost to follow up. The mean follow up period was 9.4 yrs. 35 (83.3%) patients are in NYHA Class I and free of all medications except warfarin. 3 (7.1%) patients have undergone 5 successful pregnancies. The median INR was 2.23. Major thrombo-embolic episode occurred in 1 (2.3%) patient. Conclusions In view of the problems of sizing, anticoagulation and need for re-operation at an early age, there is a reluctance to replace valves in children. This study shows that despite these problems, valve replacement can be undertaken safely and successfully in children, when repair has failed or not technically feasible.     

Awareness of warning symptoms and risk factors of stroke in the general population and in survivors stroke.

Awareness among the general population of the risk factors and warning symptoms of stroke is essential for preventative purposes and for immediate effective treatment. The aim of the present study was to assess the awareness, among the general population and stroke survivors, of the risk factors and warning symptoms of stroke, to develop an educational strategy for its prevention and immediate effective treatment. Six hundred and sixty stroke patients (370 male, 290 female) and 4000 people from the general population who accompanied the patients (2800 male, 1200 female) were interviewed, using three sets of questionnaires, on the risk factors and warning symptoms of stroke. Poor knowledge or awareness of the risk factors and warning symptoms of stroke was found in both groups. Both groups suggested educational programs for stroke using printed information, audiovisual programs and community survey programs using simple and understandable information for the prevention and immediate effective treatment of stroke. Poor awareness of stroke contributes to a delay in the arrival of patients in hospital emergency departments for immediate effective treatment. Multifaceted programs regarding stroke, including printed information, audiovisual programs and stroke service programs, are advocated by both patients and the general population to improve stoke treatment and prevention.     

Automatic algorithm for correcting motion artifacts in time-resolved two-dimensional magnetic resonance angiography using convex projections.

Time-resolved contrast enhanced magnetic resonance angiography (MRA) may suffer from involuntary patient motion. It is noted that while MR signal change associated with motion is large in magnitude and has smooth phase variation in k-phase, signal change associated with vascular enhancement is small in magnitude and has rapid phase variation in k-space. Based upon this observation, a novel projection onto convex sets (POCS) algorithm is developed as an automatic iterative method to remove motion artifacts. The presented POCS algorithm consists of high-pass phase filtering and convex projections in both k-space and image space. Without input of detailed motion knowledge, motion effects are filtered out, while vasculature information is preserved. The proposed method can be effective for a large class of nonrigid motions, including through-plane motion. The algorithm is stable and converges quickly, usually within five iterations. A double-blind evaluation on a set of clinical MRA cases shows that a completely unsupervised version of the algorithm produces significantly better rank scores (P=0.038) when compared to angiograms produced manually by an experienced radiologist.     

Simultaneous Quantification of an Enantiomer and the Racemic Compound of Ibuprofen by X-ray Powder Diffractometry

Purpose. An X-ray powder diffractometric method was developed for the simultaneous quantification of the relative amounts of the racemic compound (±) of ibuprofen (I) and S(+)-ibuprofen (II), when they occur as a mixture. Methods. The X-ray powder diffraction patterns of I and II show pronounced differences. This formed the basis for the determination of the relative amounts of I and II when they occur as a mixture. X-ray lines with d-spacings of 14.41 and 4.37 Å were unique to I and II, respectively. Mixtures containing different proportions of I and II were prepared which also contained lithium fluoride (III) as an internal standard. Results. A linear relationship was obtained when the intensity ratio (intensity of the 4.37 Å line of II/intensity of the 2.01 Å line of III) was plotted as a function of the weight fraction of II in the mixture. Similar results were obtained in the case of I. Using these standard curves, the weight fractions of I and II in 'unknown' mixtures were determined. The experimentally determined analyte concentration ranged between 98 and 104% of the true value. The relative error in the analyses of individual samples was < 10%. The minimum detectable weight fraction of I in II and II in I were 0.032 (3.2% w/w) and 0.034 (3.4% w/w), respectively. The minimum quantifiable weight fractions were 0.136 for I and 0.112 for II. Since the X-ray diffraction patterns of S(+)-ibuprofen and R(–)-ibuprofen are identical, the conclusions drawn regarding mixtures of I and II will also hold true in the quantitative analyses of mixtures of I and R(–)-ibuprofen.     

Virtual histology intravascular ultrasound in carotid interventions.

PURPOSE: To report early clinical experience with virtual histology intravascular ultrasound (VH IVUS) in carotid endoluminal repair. TECHNIQUE: A 2.9-F, 20-MHz catheter that utilizes computer software to demonstrate the histological components of arteriosclerotic plaque was evaluated during carotid angioplasty and stenting. VH IVUS images were created following a pullback through the carotid stenosis and produced a color-coded map of the different histological constituents of the disease (dark green: fibrous, yellow/green: fibrofatty, white: calcified, and red: necrotic lipid core plaque). CONCLUSION: VH IVUS produces a color-coded map of the different histological components of artery plaque. It has the potential to predict how the plaque is likely to behave at the moment of endoluminal treatment.