Hypoxia-associated markers are involved in the progression of several malignancies, but are relatively unstudied in Barrett's carcinogenesis. Our aim was to assess the immunohistochemical expression of hypoxia-inducible factor (HIF)-1a, HIF-2a, erythropoietin (Epo), Epo receptor (Epo-R), Glut-1 and vascular endothelial growth factor (VEGF) along with Ki67/MIB-1 in the Barrett's metaplasia -dysplasia -adenocarcinoma sequence. Endoscopic biopsies of normal squamous epithelium (NSE) (n ¼ 20), columnar-lined oesophagus (CLO) (n ¼ 15), CLO with intestinal metaplasia (n ¼ 20), dysplasia (n ¼ 17) and Barrett's type adenocarcinoma (n ¼ 20) were obtained. Immunohistochemistry was performed on the paraffin-embedded tissue. A score was calculated for each marker (range 0À300) by multiplying intensity (none 0, weak 1, moderate 2, strong 3) by percentage of expression (range 0 -100). Significant increases in the expression of HIF-2a (P ¼ 0.014), VEGF (Po0.0001), Epo-R (Po0.0001) and Ki67 (Po0.0001) were found as tissue progressed from NSE to adenocarcinoma. HIF-2a was expressed late in the sequence and was only seen in dysplasia and adenocarcinoma. High HIF-2a expression was seen in 12 out of 20 Barrett's type adenocarcinoma. The late expression of HIF-2a in the Barrett's carcinogenesis sequence and its high expression in adenocarcinoma suggest that it is worth further investigation as a marker of disease progression and therapeutic target.

The study investigated hypoxia-associated markers (HIF-2a, Epo, Epo-R, Glut-1 and VEGF) along with Ki-67 in a gastric carcinogenesis model, and the prognostic significance of hypoxia-inducible factor (HIF)-2a in surgically treated gastro-oesophageal cancer. Protein expression was examined using immunohistochemistry on formalin-fixed, paraffin-embedded biopsies of normal mucosa (n ¼ 20), Helicobacter pylori-associated gastritis (n ¼ 24), intestinal metaplasia (n ¼ 24), dysplasia (n ¼ 12) and intestinal (n ¼ 19) and diffuse (n ¼ 21) adenocarcinoma. Relationships between HIF-2a expression and prognosis were assessed in resection specimens from 177 patients with gastric and gastro-oesophageal junction adenocarcinoma. Expression of all markers increased with progression along the gastric carcinogenesis sequence (P ¼ 0.0001). Hypoxia-inducible factor-2a was expressed in 63% of 177 resection specimens and at a high level in 44%. The median overall survival in patients with HIF-2a-expressing tumours was 22 (95% CI 18À26) months, whereas those with HIF-2a-negative tumours had a median survival of 37 (95% CI 29À44) months (P ¼ 0.015). Hypoxia-inducible factor-2a had no independent prognostic significance in multivariate analysis. In view of the lack of independent prognostic significance, HIF-2a has no role as a routine prognostic indicator. However, the high expression of HIF-2a suggests that it may be of value as a potential therapeutic target.

Study Design. Retrospective review with qualitative phone interview. Objective. This study aims to identify the factors leading to delayed diagnosis or referral to a spinal surgeon in patients who subsequently require surgery for adolescent idiopathic scoliosis (AIS). Summary of Background Data. AIS can be effectively treated with bracing to prevent curve progression in skeletally immature patients. Australia currently has in place a national self-detection screening program to diagnose AIS. Methods. A retrospective review was performed for patients who underwent surgery for scoliosis at Princess Margaret Hospital for Children and Royal Perth Hospital between June 1, 2010 and May 27, 2014. Data were retrieved from the digital medical record and a semistructured phone interview was used to determine path to diagnosis and referral. Results. Mean Cobb angle at first specialist review was 49.5° ± 14.0° for patients who subsequently required surgery for AIS. These patients experienced an average interval of 20.7 months from detection of symptoms to review in a specialist clinic. Conclusion. In a condition in which early detection and intervention may halt progression of disease, AIS is detected relatively late and there are specific delays to diagnosis and referral to specialist clinics. Level of Evidence: 4

Intravenous Tranexamic acid has been shown to decrease blood transfusion requirements in surgery. Little evidence exists regarding the much cheaper oral form. The objective of this cohort study was to evaluate whether oral tranexamic acid administration in patients undergoing elective hip and knee replacement surgery resulted in decreased transfusion requirements. Methods: We assessed the transfusion requirements of 332 patients following unilateral total hip or knee arthroplasty, with the first 140 receiving no tranexamic acid and the next 192 given 1 g oral tranexamic acid one hour prior to and a further 1 g 4 hours post joint arthroplasty. Haemoglobin before and after surgery, the number of units transfused post-operatively and the incidence of deep vein thrombosis or pulmonary embolism were recorded. Results: In the first group, there were 22 instances of transfusion (15.7%) and a mean haemoglobin drop of 32.2 g/L, while the second (tranexamic acid) group had just 12 patients transfused (6.3%) and a mean haemoglobin drop of 24.6 g/L (both significantly less, p < 0.01). There was no significant difference in deep vein thrombosis or pulmonary embolism rates between groups. Conclusions: This is the first prospective study to analyze the outcome of oral tranexamic acid administration in hip and knee replacement. We conclude that oral tranexamic acid administration is a safe and effective means to decrease transfusion requirements in joint arthroplasty and is a much cheaper alternative to intravenous preparations of tranexamic acid.

Examining lymph nodes at three levels did detect more metastatic deposits than examination of one section/level. In six patients this changed the N stage from N0 to N1. This would have significant prognostic and management implications.