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.     

Factors affecting compliance to intravitreal anti-vascular endothelial growth factor therapy in Indian patients with retinal vein occlusion,age-related macular degeneration,and diabetic macular edema

Purpose:To evaluate the rate of compliance and the reasons for loss to follow-up in Indian patients with diabetic macular edema (DME), age-related macular degeneration (AMD), and retinal vein occlusion (RVO) being treated with anti-vascular endothelial growth factor (VEGF) therapy.Methods:This was a retrospective single-center study. Patients with DME, AMD, or RVO were eligible if they initiated anti-VEGF therapy between January 2013 and December 2017. Patients'' data were obtained from hospital electronic records, including the number of injections received, visits, details of follow-up, missed appointments, and reasons for loss to follow-up (>365 days).Results:A total of 648 patients were eligible for the study, of which 334 (51.54%) patients were lost to follow-up. Overall, 343 (64.96%) were males and the overall mean (SD) age was 66.40 (7.44) years. A total of 376 (58.0%) patients had a history of diabetes and 364 (56.2%) patients had a history of hypertension. Further, 127 (38.0), 112 (33.5), and 95 (28.4) had DME, AMD, and RVO, respectively and were lost to follow-up. The most commonly reported reason for loss to follow-up was “non-affordability” (n = 120; 41.1%) followed by “no improvement in vision” (n = 83; 28.4%). “No improvement in vision” (42.2%) and “non-affordability” (37.5%) were higher among patients with DME. No association was found in gender- and treatment-wise distribution of reasons for loss to follow-up.Conclusion:The results showed that around half of the patients with DME, AMD, and RVO were lost to follow-up to intravitreal anti-VEGF therapy, and the most common factors were “non-affordability” and “no improvement in vision.”     

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.     

Tubercular pseudoaneurysm of aorta: a rare association with vertebral tuberculosis.

BACKGROUND CONTEXT: Pseudoaneurysm of the aorta in association with vertebral tuberculosis is a rare phenomenon. With the resurgence of human immunodeficiency virus (HIV) and associated resistant tuberculosis, this life-threatening complication requires greater awareness. PURPOSE: Our purpose is to report the rare presentation and successful management of tubercular pseudoaneurysm of the aorta in association with vertebral tuberculosis, and to highlight the clinicoradiological features for early and prompt diagnosis of this potentially fatal, but treatable, disease. STUDY DESIGN: A single case report and overview of the disease comprises the design of this study. PATIENT SAMPLE: The patient, already surgically intervened, is a 27-year-old male with increasing abdominal and back pain, upper motor neuron signs, and constitutional signs and symptoms. OUTCOME MEASURES: At 33 months follow-up, there is complete resolution of the signs and symptoms, and the patient is back to his previous vocation. METHODS: The diagnosis was confirmed by magnetic resonance imaging and contrast computed tomography. Endoaneurysmorrhaphy of the pseudoaneurysm along with a complete course of antitubercular treatment was given to the patient, and he has presently been followed up for 33 months. RESULTS: The patient's signs and symptoms have been completely resolved without any recurrence. CONCLUSION: Despite the use of modern chemotherapy and imaging techniques, this disastrous complication still occurs and reinforces the need for early suspicion, diagnosis, surgical resection, and antitubercular therapy along with close postoperative follow-up to prevent recurrence. With the resurgence of HIV (and other immunocompromised states) associated and resistant tuberculosis, we should be more alert than ever to this life-threatening complication.     

Ewing's tumour of rib presenting as chest mass

A case of Ewing's tumour of rib presenting as chest mass is reported. The role of computed tomography and chest ultrasound in evaluating such patients is discussed along with a brief review of literature.     

Pediatric intracranial aneurysms—clinical characteristics and outcome of surgical treatment

Object Intracranial aneurysms are rare in children and have different epidemiological, clinical, and morphological characteristics and outcome from those in adults. Materials and methods We analyzed demographic, clinical, radiologic features, treatment, and outcome in 55 patients <18 years of age, treated from Jan 1995 through December 2005. Results Intracranial aneurysms in children below 18 years constituted 4% of all intracranial aneurysms. Internal Carotid artery (ICA) bifurcation was the commonest location. About half of the aneurysms were complex. Three-fourth of the patients required surgical treatment. Two patients died, constituting 5% mortality. Two patients (5%) had poor outcome, whereas the majority (90%) had a favorable outcome. Conclusions Pediatric aneurysms have male predominance, higher incidence of clinical features of mass effect or seizures, high incidence of large, traumatic/mycotic aneurysms, associated illnesses and ICH/IVH and hydrocephalus, better Hunt and Hess grades at presentation, ICA bifurcation as the commonest site, and better outcome than their adult counterparts.     

Binding of nonsteroidal anti-inflammatory agents and their effect on binding of racemic warfarin and its enantiomers to human serum albumin

The binding of racemic warfarin, its enantiomers, and several nonsteroidal anti-inflammatory agents to human serum albumin was investigated by equilibrium dialysis at 4 degrees C in pH 7.4 phosphate buffer. The primary binding constant for the S(-) enantiomer of warfarin was approximately two times greater than the corresponding binding of the R(+) enantiomer. The effect of azapropazone, phenylbutazone, naproxen, ibuprofen, mefenamic acid, and tolmetin on the binding of racemic warfarin and its enantiomers was studied. Warfarin was displaced by all of the nonsteroidal anti-inflammatory agents except tolmetin. Azapropazone caused the largest displacement of warfarin (39 to 46% free warfarin versus 2.5 to 6% free warfarin without competing drug), followed by phenylbutazone (23 to 43% free warfarin), naproxen (9 to 24% free warfarin), mefenamic acid (5 to 11.5% free warfarin), and ibuprofen (5 to 9% free warfarin). Azapropazone and phenylbutazone competed with warfarin for the same primary binding site on the albumin molecule. Naproxen appeared to affect warfarin binding at both primary and secondary sites. Ibuprofen and mefenamic acid interfered with the binding of warfarin at its secondary sites. In contrast to the other drugs studied, tolmetin caused an increase in the primary binding constant of warfarin. Structural analysis indicated that a common feature of those compounds which primarily bind at the warfarin site is a hydrophobic area bearing a widely delocalized negative charge.