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.     

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.     

Screw angulation affects bone-screw stresses and bone graft load sharing in anterior cervical corpectomy fusion with a rigid screw-plate construct: a finite element model study

Background contextAnterior corpectomy and reconstruction with bone graft and a rigid screw-plate construct is an established procedure for treatment of cervical neural compression. Despite its reliability in relieving symptoms, there is a high rate of construct failure, especially in multilevel cases.PurposeThere has been no study evaluating the biomechanical effects of screw angulation on construct stability; this study investigates the C4–C7 construct stability and load-sharing properties among varying screw angulations in a rigid plate-screw construct.Study designA finite element model of a two-level cervical corpectomy with static anterior cervical plate.MethodsA three-dimensional finite element (FE) model of an intact C3–T1 segment was developed and validated. From this intact model, a fusion model (two-level [C5, C6] anterior corpectomy) was developed and validated. After corpectomy, allograft interbody fusion with a rigid anterior screw-plate construct was created from C4 to C7. Five additional FE models were developed from the fusion model corresponding to five different combinations of screw angulations within the vertebral bodies (C4, C7): (0°, 0°), (5°, 5°), (10°, 10°), (15°, 15°), and (15°, 0°). The fifth fusion model was termed as a hybrid fusion model.ResultsThe stability of a two-level corpectomy reconstruction is not dependent on the position of the screws. Despite the locked screw-plate interface, some degree of load sharing is transmitted to the graft. The load seen by the graft and the shear stress at the bone-screw junction is dependent on the angle of the screws with respect to the end plate. Higher stresses are seen at more divergent angles, particularly at the lower level of the construct.ConclusionThis study suggests that screw divergence from the end plates not only increases load transmission to the graft but also predisposes the screws to higher shear forces after corpectomy reconstruction. In particular, the inferior screw demonstrated larger stress than the upper-level screws. In the proposed hybrid fusion model, lower stresses on the bone graft, end plates, and bone-screw interface were recorded, inferring lower construct failure (end-plate fractures and screw pullout) potential at the inferior construct end.