The Rationale for Repurposing Sildenafil for Lung Cancer Treatment.

There is now a considerable body of evidence for sildenafil possessing anticancer properties. In this article, we argue the case for testing sildenafil as a lung cancer therapy chemoadjuvant. Currently, lung cancer is a disease with insufficient treatment options, with only 20% of patients responding to systemic chemotherapy, and even incremental potential improvements should be explored. We review the literature concerning the biochemical, physiological and metabolic effects on cancer cells by sildenafil alone, and when combined with chemotherapeutic agents. Most studies have shown that sildenafil is cytotoxic to cancer cells, both as a monotherapy and as a chemoadjuvant. Sildenafil enhances cancer cell apoptosis when used as a chemoadjuvant both in vitro and in vivo. In particular, in rodent experiments sildenafil has decreased tumour size compared to chemotherapy alone. Sildenafil has also been proven as an agent to decrease drug-efflux by cancer cells and increases blood perfusion to lung tissue, which can potentially increase the dosage of chemotherapeutic agents delivered to lung cancer cells compared to healthy tissue. In addition, the proven clinical effects of sildenafil on other lung diseases suggest that it could improve other patient outcomes, such as right ventricular function and quality of life. Sildenafil may also extend the half-life of docetaxel and some small molecule inhibitors used in lung cancer treatment by acting as an inhibitor of CYP3A4. We conclude that the evidence strongly warrants clinical investigation into the use of sildenafil as an agent for the treatment of lung-cancer.

Soft tissue calcifications in the lower extremities of severely diabetic patients simulating venous stasis or collagen vascular disease.

The purpose of this work is to report soft tissue calcifications in severely diabetic patients that simulate venous stasis or scleroderma, without other stigmata of these diseases. Findings from lower extremity radiographs were reviewed on two patients with severe diabetes mellitus and abnormal soft tissue calcifications. Findings were correlated with clinical history, physical exam findings, and laboratory values. Both patients in this study demonstrate radiographic findings of lower extremity soft tissue calcifications similar to those seen in venous stasis or scleroderma. Clinical history, physical examination, and laboratory values support severe diabetes mellitus, with no evidence of these other disease entities. Patients with severe diabetes mellitus may exhibit soft tissue calcifications of their lower extremities that may simulate the changes of venous stasis or scleroderma. This association has not been previously described.

Degeneration of the costovertebral articulation: a cause of pulmonary pseudolesion.

The objective was to report examples of degeneration of the costovertebral articulation producing a pulmonary pseudolesion. Three cases in which a nodular opacity seen on plain radiograph was determined to be secondary to degeneration of the costovertebral articulation were compiled, one of which was confirmed by CT. Pseudolesions produced by degenerative osteophytes of the vertebral spine and anomalous articulations between transverse processes are more commonly identified, but less well described is the pseudolesion produced by degeneration of the costovertebral articulation. Recognition of this etiology may prevent misconstruing the lesion as a significant finding.

Management of common stress fractures. When to apply conservative therapy, when to take an aggressive approach.

Stress fractures are an increasingly common injury in primary care patient populations. Early diagnosis and prompt conservative therapy are effective for most of these injuries. Special attention to clues from history taking and physical examination in an at-risk patient population can lead physicians to the correct diagnosis. Most stress fractures resolve with rest and progressive reintroduction of stressors, but certain injuries, such as stress fractures of the femoral neck and fifth metatarsal, have a high risk of complications and require aggressive therapy.