Long-term quality of life among localised prostate cancer survivors: QALIPRO population-based study

BackgroundTo evaluate quality of life (QoL) 10 years after treatments for localised prostate cancer (LPCa) patients in comparison with aged-matched healthy controls.MethodsLPCa patients diagnosed in 2001 were obtained from 11 French cancer registries. Controls were recruited among the general population and were matched to patients on age and geographic area. EORTC Quality of Life Questionnaire – Core 30 items, Expanded Prostate Cancer Index Composite, Hospital Anxiety and Depression Scale and Multidimensional Fatigue Inventory self-reported questionnaires were used to measure QoL, anxiety and fatigue. Patients were classified in three groups according to previous treatments: radical prostatectomy (RP), radiotherapy (RT) and radical prostatectomy and radiotherapy (RP+RT). The differences in QoL between patients and controls and according to treatment groups were evaluated.ResultsThere were 287 patients and 287 controls. There was no socio-demographic difference between patients and controls. Treatments were: RP (143), RT (78), PR+RT (33), baseline hormone therapy (49) and hormone therapy at the time of the study (34). Patients had similar levels of global QoL, anxiety, depression and fatigue as controls. They reported more urinary troubles (urinary function and incontinence) (p < 0.0001) and more sexual dysfunctions (p < 0.0001) than controls, whatever the treatment group. Worse bowel dysfunction was reported in patients treated by RT and RP+RT (p < 0.002). According to the treatments, RP groups had the worst urinary function and incontinence (p < 0.01), and reported more bowel bother when the treatment was combined with RT.ConclusionsEven though patients reported similar global QoL as control 10 years after treatment, patients reported numerous urinary and sexual dysfunctions. Patients treated with RP+RT reported cumulative sequelae of both treatments.     

Using unique molecular identifiers to improve allele calling in low-template mixtures

PCR artifacts are an ever-present challenge in sequencing applications. These artifacts can seriously limit the analysis and interpretation of low-template samples and mixtures, especially with respect to a minor contributor. In medicine, molecular barcoding techniques have been employed to decrease the impact of PCR error and to allow the examination of low-abundance somatic variation. In principle, it should be possible to apply the same techniques to the forensic analysis of mixtures. To that end, several short tandem repeat loci were selected for targeted sequencing, and a bioinformatic pipeline for analyzing the sequence data was developed. The pipeline notes the relevant unique molecular identifiers (UMIs) attached to each read and, using machine learning, filters the noise products out of the set of potential alleles. To evaluate this pipeline, DNA from pairs of individuals were mixed at different ratios (1−1, 1−9) and sequenced with different starting amounts of DNA (10, 1 and 0.1 ng). Naïvely using the information in the molecular barcodes led to increased performance, with the machine learning resulting in an additional benefit. In concrete terms, using the UMI data results in less noise for a given amount of drop out. For instance, if thresholds are selected that filter out a quarter of the true alleles, using read counts accepts 2381 noise alleles and using raw UMI counts accepts 1726 noise alleles, while the machine learning approach only accepts 307.     

Long-term follow-up of axillary node-positive breast cancer patients receiving adjuvant tamoxifen alone: patterns of recurrence

Purpose: To determine the patterns, incidence and risk factors for local-regional recurrence in patients with Stage II and III breast cancer treated with adjuvant tamoxifen alone, without adjuvant radiation.Material and Methods: The records of patients referred to the London Regional Cancer Centre with a diagnosis of breast cancer between 1980–1989 were reviewed. During this time period, it was the policy of the institution to omit local-regional radiation to patients receiving adjuvant systemic therapy. One hundred and fifty axillary node-positive Stage II and III breast cancer patients received adjuvant tamoxifen alone without postoperative local-regional radiation; these patients form the basis of this report.Results: Median follow-up was 67 months for the entire patient group and 85 months for the living patients. During this time, 42% of patients developed a recurrence, 22% first recurred in local-regional sites. The total incidence of local-regional recurrence (including those patients who first relapsed with systemic metastases) was 30%. Of the segmental mastectomy patients, 13% had recurrences in the intact breast. Of the modified radical mastectomy patients, 10% developed chest wall recurrences. Five percent of recurrences were first in the axilla and 6% in the supraclavicular nodes. Five-year actuarial survival for the entire patient group was 79% and disease-free survival was 60%, with a median disease-free survival time of 87 months. Five-year local-regional relapse-free survival was 76%. Five-year local-regional relapse-free survival was < 76% for those patients with 4 or more positive axillary nodes, regardless of tumor size. On univariable analysis, positive resection margins, number of positive axillary nodes, menopausal status, and negative estrogen and progesterone receptors were significant for isolated local-regional recurrence. On multivariable analysis, only positive resection margins and negative receptors remained significant. In terms of regional recurrence specifically, negative estrogen and progesterone-receptor status and positive resection margins were, again, prognostically significant.Conclusions: Postmenopausal women receiving adjuvant tamoxifen who have positive resection margins, ≥ 4 positive axillary nodes and/or negative estrogen and progesterone receptors, are at higher risk of local and regional recurrence and should, therefore, receive local-regional radiation.     

Current trends in the study of potassium channel openers

Some eight years ago it was found that certain smooth muscle relaxants exert their effect by opening a specific K⁺ channel resulting in cell membrane hyperpolarization. The use of K⁺channel openers (cromakalim, pinacidil and RP-52891) and compounds which antagonize their actions (glibenclamide, phentolamine and alinidine) has enabled a great deal of research to be performed into the role of this K⁺ channel, not only in smooth muscle, but also in cardiac and skeletal muscle as well as neural and endocrine organ function. Much of the attention has centred on the smooth muscle relaxant actions of the K⁺ channel openers, since they have potential therapeutic use in disorders involving smooth muscle over-reactivity such as hypertension and asthma. More recently the cardiac actions of the K⁺ channel openers have become the focus of interest. Although there appear to be good theoretical reasons why K⁺ channel openers may be of use in some arrhythmias and in ischaemic heart disease there are major hurdles to overcome. In particular, given that the effect of these compounds on vascular smooth muscle occurs at a concentration 20- to 100-fold lower than that required to produce cardiac effects, it is likely their therapeutic usefulness will be limited until a breakthrough in cardiac/vascular selectivity is made. There is also growing interest in endogenous K⁺ channel openers and the physiological role of the K⁺ channel which they open. Opening of K⁺ channels, either spontaneously or by endogenous regulators, could possibly be an important hypotensive mechanism both under normal conditions and in a number of pathological conditions. Research into these areas will need to continue if the true therapeutic potential of K⁺ channel openers and their antagonists are to be realized.