Repeated White Light Transurethral Resection of the Bladder in Nonmuscle-Invasive Urothelial Bladder Cancers: Systematic Review and Meta-Analysis.

J Endourol. 2011 Sep 21;

Authors: Vianello A, Costantini E, Del Zingaro M, Bini V, Herr HW, Porena M

Abstract
Abstract Background and Purpose: Transurethral resection of the bladder (TURB), the first step in treatment of patients with urothelial bladder cancers, is limited by technicalities, surgeon skill, and random chance. When high-risk superficial diseases are discovered, a repeated TURB is indicated. We reviewed current literature and performed a meta-analysis of the role of repeated TURB in the management of nonmuscle-invasive bladder cancers. Methods: PubMed, MEDLINE, ISI Web of Knowledge, EBSCO, EMBASE, and Biomed Central databases were searched for reports in English from 1980 to June 2010. The end point was prevalence of persistent urothelial bladder cancer of any stage and grade at repeated TURB, assessed separately for T(a) and T(1) lesions at TURB. Persistence was presence at repeated TURB of same or lower stage cancer as at TURB; upstaging was presence of higher stage. Results: There were 2327 original articles and 562 reviews retrieved. Data from 15 studies were pooled and analyzed. Prevalence of T(1) was reported in all and of T(a) in 8. Persistence rate prevalence at repeated TURB was 0.39 (95% confidence interval [CI]=0.26 to 0.54) for T(a) and 0.47 (95% CI=0.41 to 0.53) for T(1). Persistence was 19.4% to 56% and 15.2% to 55%, and upstaging occurred in 0% to 14.3% of T(a) and 0% to 24.4% of T(1) at repeated TURB, respectively. Conclusion: High percentages of persistence and upstaging confirm a repeated TURB is needed in patients with high-risk nonmuscle-invasive bladder cancer. Further investigation is encouraged taking risk stratification into consideration to evaluate the role of repeated TURB in low- and mid- risk diseases.

PMID: 21936670 [PubMed - as supplied by publisher]

Review article: common misconceptions in the management of H. pylori-associated gastric MALT-lymphoma.

Aliment Pharmacol Ther. 2011 Sep 15;

Authors: Gisbert JP, Calvet X

Abstract
Background  Helicobacter pylori infection is the main cause of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Aim  To review several common misconceptions in the management of H. pylori-associated gastric MALT-lymphoma. Methods  Bibliographical searches were performed in MEDLINE up to June 2011. Results  If adequate diagnostic methods are used, and if only low-grade lymphomas are considered, the prevalence of H. pylori infection is very high (almost 90%). H. pylori eradication is effective in treating approximately 80% of patients with early stage lymphoma. In H. pylori-positive gastric high-grade lymphomas, antibiotic therapy should always be prescribed, as approximately 50% of them regress after H. pylori eradication. Patients with early stage MALT lymphoma negative for H. pylori might still benefit from antibiotic treatment as the sole treatment. Complete remission of gastric MALT lymphoma after H. pylori eradication can take even >12 months. PCR assay for the detection of monoclonal B cells remains positive in many cases after complete remission has been reached. Patients with a persistent clonal band should not be treated unless the lymphoma can be histologically demonstrated. Synchronous occurrence of gastric adenocarcinoma and MALT lymphoma has been repeatedly reported. In some patients in complete remission, eradication of H. pylori does not prevent later development of early gastric cancer. Gastric lymphoma recurrence occurs in some patients after both bacterial and lymphoma regression. H. pylori reinfection does not constitute a prerequisite for lymphoma recurrence. Conclusions  The present article states several misconceptions in the management of H. pylori-associated gastric MALT-lymphoma in clinical practice, reviews the related scientific evidence and proposes the adequate attitude in each case.

PMID: 21919927 [PubMed - as supplied by publisher]

Revascularisation and mortality rates following acute coronary syndromes in people with severe mental illness: comparative meta-analysis.

Br J Psychiatry. 2011 Jun;198(6):434-41

Authors: Mitchell AJ, Lawrence D

Abstract
BACKGROUND: High levels of comorbid physical illness and excess mortality rates have been previously documented in people with severe mental illness, but outcomes following myocardial infarction and other acute coronary syndromes are less clear.
AIMS: To examine inequalities in the provision of invasive coronary procedures (revascularisation, angiography, angioplasty and bypass grafting) and subsequent mortality in people with mental illness and in those with schizophrenia, compared with those without mental ill health.
METHOD: Systematic search and random effects meta-analysis were used according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies of mental health and cardiovascular procedures following cardiac events were eligible but we required a minimum of three independent studies to warrant pooling by procedure type. We searched Medline/PubMed and EMBASE abstract databases and ScienceDirect, Ingenta Select, SpringerLink and Online Wiley Library full text databases.
RESULTS: We identified 22 analyses of possible inequalities in coronary procedures in those with defined mental disorder, of which 10 also reported results in schizophrenia or related psychosis. All studies following acute coronary syndrome originated in the USA. The total sample size was 825 754 individuals. Those with mental disorders received 0.86 (relative risk, RR: 95% CI 0.80-0.92, P<0.0001) of comparable procedures with significantly lower receipt of coronary artery bypass graft (CABG; RR = 0.85, 95% CI 0.72-1.00), cardiac catheterisation (RR = 0.85, 95% CI 0.76-0.95) and percutaneous transluminal coronary angioplasty or percutaneous coronary intervention (PTCA/PCI; RR = 0.87, 95% CI 0.72-1.05). People with a diagnosis of schizophrenia received only 0.53 (95% CI 0.44-0.64, P<0.0001) of the usual procedure rate with significantly lower receipt of CABG (RR = 0.69, 95% CI 0.55-0.85) and PTCA/PCI (RR = 0.50, 95% CI 0.34-0.75). We identified 6 related studies examining mortality following cardiac events: for those with mental illness there was a 1.11 relative risk of mortality up to 1 year (95% CI 1.00-1.24, P = 0.05) but there was insufficient evidence to examine mortality rates in schizophrenia alone.
CONCLUSIONS: Following cardiac events, individuals with mental illness experience a 14% lower rate of invasive coronary interventions (47% in the case of schizophrenia) and they have an 11% increased mortality rate. Further work is required to explore whether these factors are causally linked and whether improvements in medical care might improve survival in those with mental ill health.

PMID: 21628705 [PubMed - indexed for MEDLINE]

The clinical effectiveness and cost-effectiveness of genotyping for CYP2D6 for the management of women with breast cancer treated with tamoxifen: a systematic review.

Health Technol Assess. 2011 Sep;15(33):1-102

Authors: Fleeman N, Martin Saborido C, Payne K, Boland A, Dickson R, Dundar Y, Fernández Santander A, Howell S, Newman W, Oyee J, Walley T

Abstract
BACKGROUND: Breast cancer is the most common cancer affecting women in the UK. Tamoxifen (TAM) is considered as the standard of care for many women with oestrogen receptor positive breast cancer. However, wide variability in the response of individuals to drugs at the same doses may occur, which may be a result of interindividual genetic differences (pharmacogenetics). TAM is known to be metabolised to its active metabolites N-desmethyl TAM and 4-hydroxytamoxifen by a number of CYP450 enzymes, including CYP2D6, CYP3A4, CYP2C9, CYP2C19 and CYP2B6. N-desmethyl TAM is further metabolised to endoxifen by CYP2D6. Endoxifen, which is also formed via the action of CYP2D6, is 30- to 100-fold more potent than TAM in suppressing oestrogen-dependent cell proliferation, and is considered an entity responsible for significant pharmacological effects of TAM. Thus, an association between the cytochrome P450 2D6 (CYP2D6) genotype and phenotype (expected drug effects) is believed to exist and it has been postulated that CYP2D6 testing may play a role in optimising an individual's adjuvant hormonal treatment.
OBJECTIVES: To determine whether or not testing for cytochrome P450 2D6 (CYP2D6) polymorphisms in women with early hormone receptor positive breast cancer leads to improvement in outcomes, is useful for health decision-making and is a cost-effective use of health-care resources.
DATA SOURCES: Relevant electronic databases and websites including MEDLINE, EMBASE and HuGENet [Centers for Disease Control and Prevention (Office of Public Health Genomics), Human Genome Epidemiology Network] were searched until July 2009. Further studies that became known to the authors via relevant conferences or e-mail alerts from an automatically updated search of the Scopus database were also included as the review progressed, up to March 2010.
REVIEW METHODS: A systematic review of the clinical effectiveness and cost-effectiveness of CYP2D6 testing was undertaken. As it was not possible to conduct meta-analyses, data were extracted into structured tables and narratively discussed. An exploratory analysis of sensitivity and specificity was undertaken. A review of economic evaluations and models of CYP2D6 testing for patients treated with TAM was also carried out.
RESULTS: A total of 25 cohorts were identified which examined clinical efficacy (overall survival and relapse/recurrence), adverse events and endoxifen plasma concentrations by genotype/phenotype. Significantly, six cohorts suggest extensive metabolisers (Ems) appear to have better outcomes than either poor metabolisers (PMs) or PMs + intermediate metabolisers in terms of relapse/recurrence; however, three cohorts report apparently poorer outcomes for EMs (albeit not statistically significant). There was heterogeneity across the studies in terms of the patient population, alleles tested and outcomes used and defined. One decision model proposing a strategy for CYP2D6 testing for TAM was identified, but this was not suitable for developing a model to examine the cost-effectiveness of CYP2D6 testing. It was not possible to produce a de novo model because of a lack of data to populate it.
CONCLUSION: This is a relatively new area of research that is evolving rapidly and, although international consortia are collaborating, the data are limited and conflicting. Therefore, it is not possible to recommend pharmacogenetic testing in this patient population. Future research needs to focus on which alleles (including, or in addition to, those related to CYP2D6) reflect patient response, the link between endoxifen levels and clinical outcomes, and the appropriate pathways for implementation of such pharmacogenetic testing in patient care pathways.
FUNDING: The National Institute for Health Research Health Technology Assessment programme.

PMID: 21906462 [PubMed - in process]