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.     

Self-Mutilation in Neurodegeneration with Brain Iron Accumulation

Neurodegeneration with brain iron accumulation (NBIA) is the term applied to a heterogeneous group of disorders resulting in iron deposition in the basal ganglia. Well-known phenotypic features are progressive regression with extra pyramidal involvement and a variable course. A 10-year-old child born to consanguineous parents presented with progressive generalized opisthotonic dystonia, retrocollis, oromandibular dyskinesias, apraxia for swallowing, optic atrophy and severe self-mutilation of lips. MR imaging showed brain iron accumulation. Other causes of self-mutilation were excluded. Early infantile onset, ophisthotonic dystonia with oromandibular dyskinesias and characteristic MR images are suggestive of NBIA. There is only one case reported in the literature of self-mutilation in this condition.     

The use of cadaver models to diagnose rib fractures: A pilot study

Background

In the emergency department, rib fractures are a common finding in patients who sustain chest trauma. Rib fractures may be a sign of significant, underlying pathology, especially in the elderly patients where rib fractures are associated with significant morbidity and mortality. To date, no studies have evaluated the ability of ultrasound to detect rib fractures using cadaver models and subsequently use this model as a teaching tool.

An amalgam of pathogenic and beneficial endophytic fungi colonizing four Dendrobium species from Meghalaya,India

Endophytic fungi are known to play an important role in driving the evolution of plants by conferring adaptational advantages to their host through the production of secondary metabolites and phytohormones. In this study, we evaluated the diversity and phylogenetic relationship of endophytic fungal communities from four Dendrobium species viz., Dendrobium chrysanthum, Dendrobium heterocarpum, Dendrobium hookerianum, and Dendrobium longicornu of Meghalaya, India. A total of 51 culturable endophytic fungi were isolated from the four selected orchid species. The isolates were identified based on nuclear large subunit sequences into 33 species. Approximately 91% of the isolates showed affinity to Ascomycetes, while 9% of the isolates showed BLAST search similarity to Basidiomycetes. The most common genera were Trichoderma and Xylaria. The most prevalent genera were Fusarium, which was detected in all the four Dendrobium species followed by Diaporthe, which was present in three Dendrobium species viz., D. chrysanthum, D. hookerianum, and D. heterocarpum. The Shannon index value of endophytic fungal communities was the highest in D. chrysanthum (2.66), while D. longicornu (1) had the highest Evenness index. The present study revealed that endophytic fungi in these orchids are an amalgam of pathogenic and beneficial fungi, which have, at the least, switched their lifestyle to asymptomatic endophyte in their host. To our knowledge, this is the first such report on the diversity of endophytic fungi in the four selected Dendrobium species from Meghalaya, India.     

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.