More trouble ahead; is gene therapy coming of age?

BACKGROUND: A recent incident, the halting of a Phase I/II trial utilising an adeno-associated vector, highlights the fact that there are more hurdles to overcome prior to a full realisation of gene therapy in the clinical arena. METHODS: The sources of information used to prepare the paper were obtained through published work on Pubmed/Medline and materials published on the US/UK governmental agency websites. RESULTS/CONCLUSION: Over the years, two fatal incidents associated with viral vector usage have been reported. Viral vectors used as carriers for gene therapy have failed in safety trials on two occasions. Also, the human immune response and the oncogenic property of the vectors have restricted the advancement of gene therapy as a therapeutic tool. Nonetheless, gene therapy has now progressed from its infancy 'proof of concept' stage, to the next stage in which we try to overcome the problems associated with therapeutic application. However, this progression has been slow as more and more setbacks have occurred. This calls for a new perspective and radical thinking about future vector development.

Brunner's gland hyperplasia at the ampulla of Vater.

Brunner's gland hyperplasia (BGH) is a diagnostic challenge where in the pathophysiology and natural history remain poorly understood. This Case Report describes BGH arising at the ampulla of Vater, causing abdominal pain and vomiting in a 46-year-old man. Owing to the inconclusive nature of imaging studies and suspicious intraoperative findings, a Whipple resection was performed without any complications. Histological analysis showed that the obstructing lesion was BGH, with no evidence of malignancy. This is only the second such case of its kind at the ampulla of Vater to be reported. In addition, we present the previously unreported endoscopic ultrasound findings. The subsequent literature review focuses on the pathophysiology, clinical presentation, diagnosis and management of BGH.

Systematic cavity shaves reduces close margins and re-excision rates in breast conserving surgery.

The role of cavity shaves in reducing re-excision rates in breast conserving surgery (BCS) remains unclear. We compared rates of close margins and re-excision following cavity shaves based on either intraoperative radiology or systematic cavity shaves. Data was recorded prospectively from 1999 to 2003 for 217 patients undergoing BCS. For the first 106 cases, cavity shaves were performed when intraoperative radiological margins appeared close (<10 mm). The remaining 111 cases had systematic superior and inferior cavity shaves (SSICS). Close margins and re-excision rates were compared between groups. The median weight of excised tissue was less in group two: 82.8 g versus 100.5 g, P=0.001. SSICS reduced close margins by 83% (18/106 versus 8/111), OR 0.17, 95% CI 0.08-0.48, P=0.001. Multivariate analysis showed SSICS also reduced re-excision rates (15 versus 8 cases), OR 0.26, 95% CI 0.09-0.74, P=0.012. SSICS reduces close margins and re-excision rates. This approach has additional cosmetic benefits because less tissue is excised.

Percutaneous endoscopic gastrostomy: 30-day mortality trends and risk factors.

BACKGROUND AND AIMS: 30-day Percutaneous endoscopic gastrostomy (PEG) mortality of 8% (1992). Recent concerns suggest that mortality may have increased, prompting a comparison of current practice with that reported earlier. MATERIALS AND METHODS: Data regarding PEG insertion with relation to case mix, complications, 30-day mortality and associated risk factors, in 2002, in a British University Hospital was compared with that in 1992. Logistic regression analysis was used to determine factors independently predictive of 30-day mortality. RESULTS: In 2002, 112 patients (70% males, mean age 67.5 years; 1992: 63.6 years) underwent PEG. The 30-day mortality increased significantly from 8% (1992) to 22% (2002), P= 0.03. During this time, PEG insertion rate increased ten-fold, however, procedure-related mortality decreased from 2% to nil. In terms of percentage, the indications for PEG in 1992 and 2002 respectively were: cerebrovascular disease (33/25), head and neck tumours (16/24), motor neuron disease (27/11, P= 0.01). The proportion of PEGs for non-evidence-based indications increased from 16% in 1992 to 31% in 2002, P= 0.048. The number of PEGs placed radiologically increased (0/17, P= 0.02). Radiological patients received less antibiotic prophylaxis (P< 0.001) and had more PEG site infections than standard placement, P= 0.04. Multivariate analysis identified nil by mouth > or = 7 days or 11.4 (CI 3.2-41.7), albumin< or = 30 g/L or 12 (2.2-66.7) and > 1 cardiac factor or 5.1 (1.02-25.6) as independent predictors of 30-day mortality. CONCLUSIONS: The ten-fold rise in the PEG insertion rate has been accompanied by a three-fold rise in 30-day mortality. This may reflect a lowered threshold of PEG insertion. The risk factors identified may help decision-making in cases where the risk-benefit relationship is not clear-cut.

Brachial neuritis following infection with Epstein-Barr virus.

A case of brachial neuritis after infection with Epstein-Barr virus in a 15-year-old girl is presented. A review of the literature contrasts the presenting features in children and adults. Diagnostic tests, treatment and prognosis are discussed.