Retrospective Review of Chemotherapy Treatment of Locally Advanced and Metastatic Penile Cancer in the North West of England.

Aims: To examine current practices in the UK in the use of chemotherapy in advanced penile cancer and investigate the treatment outcomes of this group of patients. Study Design: Retrospective series. Place and Duration of Study: The study population received chemotherapy at Clatterbridge Cancer Centre, The Christie Hospital or Lancashire Teaching Hospital between January 1999 and January 2009. Methodology: Patients undergoing chemotherapy for histologically confirmed squamous cell carcinoma of the penis within the designated time period were identified retrospectively. Through case note review, data were collected on chemotherapy regimens, tolerability, response to treatment and survival. Response to chemotherapy was categorized by the investigators according to RECIST (version 1.0) criteria. Chemotherapy given concurrently with radiotherapy was excluded. Results: 40 patients were treated with chemotherapy for locally advanced or metastatic penile cancer. Prior to the inception of a Supra-regional Multidisciplinary Team (SMDT), seven different chemotherapy regimens were used first line. After introduction of the SMDT Cisplatin/5-Fluoruracil (5FU) was almost exclusively prescribed outside of clinical trials. 12/40 (30%) patients completed the planned course of chemotherapy. 27/40 (67%) discontinued treatment prematurely, 14/40 (35%) due to progressive disease, and 13/40 (32%) due to declining performance status and/or toxicity. Response to chemotherapy was assessed radiologically in 23/40 patients and categorised by the investigators according to RECIST criteria. There were three complete responses and eight partial responses (objective response rate 28%). Median survival was 15 months from diagnosis and 5 months from commencing first line chemotherapy. Conclusion: This supra-regional collaboration highlighted varying use of chemotherapy historically in penile cancer. Development of a supra-regional MDT has reduced much of the variability. Response rates are modest and survival outcomes are poor. This reinforces the urgent need for clinical trials to establish a framework for novel, more active regimens and to guide patient selection.

Evaluation of gene expression profiling in a mouse model of L-gulonolactone oxidase gene deficiency

Humans and guinea pigs are species which are unable to synthesize ascorbic acid (vitamin C) because, unlike rodents, they lack the enzyme L-gulonolactone oxidase (Gulo). Although the phenotype of lacking vitamin C in humans, named scurvy, has long been well known, information on the impact of lacking Gulo on the gene expression profiles of different tissues is still missing. This knowledge could improve our understanding of molecular pathways in which Gulo may be involved. Recently, we discovered a deletion that includes all 12 exons in the gene for Gulo in the sfx mouse, characterized by spontaneous bone fractures. We report here the initial analysis of the impact of the Gulo gene deletion on the murine gene expression profiles in the liver, femur and kidney.

The use of evaluation to improve the expanded programme on immunization in Mozambique

Reported are the results of an evaluation of process indicators and outputs for the Expanded Programme on Immunization (EPI) in Mozambique which were used to modify immunization strategies from 1985 to 1987. In 1986 according to cluster sample surveys, 84% of children in Maputo, the capital, were fully vaccinated. In other cities in the country, vaccination coverage increased from an average of 36% in 1985 to 55% in 1987. The major determinants of low vaccination coverage were provision of vaccination services at health centres on less than 3 days per week; missed opportunities; and vaccinating too early or with too short an interval between doses. The results of sentinel site surveillance in Maputo indicated that EPI had a marked impact on neonatal tetanus and to a lesser extent on poliomyelitis and measles. Evaluation led to changes in EPI policy in Mozambique (e.g., adoption of a uniform national vaccination schedule and discontinuation of the use of expired vaccine) and strategies (elaboration of different strategies for urban areas, rural areas, and displaced people). Also, performance was improved by involving programme managers and implementors in evaluation, and by providing timely and widespread feedback of results to policy-makers, peripheral health workers, and the community