Evolution and oncological outcomes of a contemporary radical prostatectomy practice in a UK regional tertiary referral centre

Objective To investigate the clinical and pathological trends over a ten-year period for robotic-assisted laparoscopic prostatectomy (RALP) in a UK regional tertiary referral centre. Patients and Methods 1500 consecutive patients underwent RALP between October 2005 and January 2015. Prospective data was collected on clinic-pathological details at presentation as well as surgical outcomes and compared over time. Results The median(range) age of patients throughout the period was 62(35-78) years. The proportion of pre-operative high-grade cases (Gleason sum 8-10) rose from 4.6% in 2005-2008 to 18.2% in 2013-2015 (p<0.0001). In the same periods the proportion of clinical stage T3 cases operated on rose from 2.4% to 11.4% (p<0.0001). Median PSA at diagnosis did not alter significantly. Overall 11.6% of men in 2005-2008 were classified pre-operatively as high-risk by NICE criteria, compared to 33.6% in 2013-2015 (p<0.0001). The corresponding proportions for low-risk cases were 48.6% and 17.3% respectively. Final surgical pathology demonstrated an increase in tumour stage, Gleason grade and nodal status across time. The proportion of pT3 cases rose from 43.2% in 2005-2008 to 55.5% in 2013-15 (p=0.0007), Gleason grade 9-10 tumours increased from 1.8% to 9.1% (p=0.0002) and positive nodal status increased from 1.6% to 12.9% (p<0.0001) between the same periods. Despite this, positive surgical margin rates showed a downward trend in all pT groups across the different eras (p=0.72). Conclusion This study suggests that the patient profile for RALP in our unit is changing, with increasing proportions of higher-stage and more advanced disease being referred and operated on. Surgical margin outcomes however have remained good.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1111/bju.1351

Harmonized bionomenclature – a recipe for disharmony

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149734/1/tax05035.pd

Evolution and oncological outcomes of a contemporary radical prostatectomy practice in a UK regional tertiary referral centre.

OBJECTIVE: To investigate the clinical and pathological trends, over a 10-year period, in robot-assisted laparoscopic prostatectomy (RALP) in a UK regional tertiary referral centre. PATIENTS AND METHODS: In all, 1 500 consecutive patients underwent RALP between October 2005 and January 2015. Prospective data were collected on clinicopathological details at presentation as well as surgical outcomes and compared over time. RESULTS: The median (range) age of patients throughout the period was 62 (35-78) years. The proportion of preoperative high-grade cases (Gleason score 8-10) rose from 4.6% in 2005-2008 to 18.2% in 2013-2015 (P < 0.001). In the same periods the proportion of clinical stage T3 cases operated on rose from 2.4% to 11.4% (P < 0.001). The median prostate-specific antigen (PSA) level at diagnosis did not alter significantly. Overall, 11.6% of men in 2005-2008 were classified preoperatively as high-risk by National Institute for Health and Care Excellence criteria, compared with 33.6% in 2013-2015 (P < 0.001). The corresponding proportions for low-risk cases were 48.6% and 17.3%, respectively. Final surgical pathology showed an increase in tumour stage, Gleason grade, and nodal status over time. The proportion of pT3 cases rose from 43.2% in 2005-2008 to 55.5% in 2013-2015 (P < 0.001), Gleason score 9-10 tumours increased from 1.8% to 9.1% (P < 0.001) and positive nodal status increased from 1.6% to 12.9% (P < 0.001) between the same periods. Despite this, positive surgical margin rates showed a downward trend in all pT groups across the different eras (P = 0.72). CONCLUSION: This study suggests that the patient profile for RALP in our unit is changing, with increasing proportions of higher stage and more advanced disease being referred and operated on. However, surgical margin outcomes have remained good.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1111/bju.1351

Development of an inflammatory bowel disease (IBD) Patient‐Reported Experience Measure (PREM): A patient‐led consensus work and ‘think aloud’ study for a quality improvement programme

Background Patient-Reported Experience Measures (PREMs) are key in improving healthcare quality, but no PREM exists for inflammatory bowel disease (IBD). This study aimed to co-produce a PREM with IBD service users for IBD service evaluation and quality improvement programme. Methods A pool of 75 items was drawn from published survey instruments covering interactions with services and aspects of living with IBD. In Stage 1, during two workshops, eight expert service users reduced candidate items through a ranked-choice voting exercise and suggested further items. During Stage 2, 18 previously uninvolved people with IBD assessed the face and content validity of the candidate items in ‘Think Aloud’ interviews. During two final workshops (Stage 3), the expert service users removed, modified and added items based on the interview findings to produce a final version of the PREM. Results Stage 1 generated a draft working PREM mapped to the following four domains: Patient-Centred Care; Quality; Accessibility; Communication and Involvement. The PREM included a set of nine items created by the expert group which shifted the emphasis from ‘self-management’ to ‘living with IBD’. Stage 2 interviews showed that comprehension of the PREM was very good, although there were concerns about the wording, IBD-relevance and ambiguity of some items. During the final two workshops in Stage 3, the expert service users removed 7 items, modified 15 items and added seven new ones based on the interview findings, resulting in a 38-item PREM. Conclusions This study demonstrates how extensive service user involvement can inform PREM development. Patient or Public Contribution Patients were involved as active members of the research team and as research participants to co-produce and validate a PREM for IBD services. In Stage 1, eight expert service users (‘the expert group’) reduced candidate items for the PREM through a voting exercise and suggested new items. During Stage 2, 18 previously uninvolved people with IBD (the ‘think aloud’ participants) assessed the validity of the candidate items in ‘Think Aloud’ interviews as research participants. In Stage 3, the expert group removed, changed and added items based on the interview findings to produce a final version of the 38-item PREM. This study shows how service user involvement can meaningfully inform PREM development

Shelters and Their Use by Fishes on Fringing Coral Reefs

Coral reef fish density and species richness are often higher at sites with more structural complexity. This association may be due to greater availability of shelters, but surprisingly little is known about the size and density of shelters and their use by coral reef fishes. We quantified shelter availability and use by fishes for the first time on a Caribbean coral reef by counting all holes and overhangs with a minimum entrance diameter ≥3 cm in 30 quadrats (25 m2) on two fringing reefs in Barbados. Shelter size was highly variable, ranging from 42 cm3 to over 4,000,000 cm3, with many more small than large shelters. On average, there were 3.8 shelters m−2, with a median volume of 1,200 cm3 and a total volume of 52,000 cm3m−2. The number of fish per occupied shelter ranged from 1 to 35 individual fishes belonging to 66 species, with a median of 1. The proportion of shelters occupied and the number of occupants increased strongly with shelter size. Shelter density and total volume increased with substrate complexity, and this relationship varied among reef zones. The density of shelter-using fish was much more strongly predicted by shelter density and median size than by substrate complexity and increased linearly with shelter density, indicating that shelter availability is a limiting resource for some coral reef fishes. The results demonstrate the importance of large shelters for fish density and support the hypothesis that structural complexity is associated with fish abundance, at least in part, due to its association with shelter availability. This information can help identify critical habitat for coral reef fishes, predict the effects of reductions in structural complexity of natural reefs and improve the design of artificial reefs

Integration of copy number and transcriptomics provides risk stratification in prostate cancer: A discovery and validation cohort study.

BACKGROUND: Understanding the heterogeneous genotypes and phenotypes of prostate cancer is fundamental to improving the way we treat this disease. As yet, there are no validated descriptions of prostate cancer subgroups derived from integrated genomics linked with clinical outcome. METHODS: In a study of 482 tumour, benign and germline samples from 259 men with primary prostate cancer, we used integrative analysis of copy number alterations (CNA) and array transcriptomics to identify genomic loci that affect expression levels of mRNA in an expression quantitative trait loci (eQTL) approach, to stratify patients into subgroups that we then associated with future clinical behaviour, and compared with either CNA or transcriptomics alone. FINDINGS: We identified five separate patient subgroups with distinct genomic alterations and expression profiles based on 100 discriminating genes in our separate discovery and validation sets of 125 and 103 men. These subgroups were able to consistently predict biochemical relapse (p = 0.0017 and p = 0.016 respectively) and were further validated in a third cohort with long-term follow-up (p = 0.027). We show the relative contributions of gene expression and copy number data on phenotype, and demonstrate the improved power gained from integrative analyses. We confirm alterations in six genes previously associated with prostate cancer (MAP3K7, MELK, RCBTB2, ELAC2, TPD52, ZBTB4), and also identify 94 genes not previously linked to prostate cancer progression that would not have been detected using either transcript or copy number data alone. We confirm a number of previously published molecular changes associated with high risk disease, including MYC amplification, and NKX3-1, RB1 and PTEN deletions, as well as over-expression of PCA3 and AMACR, and loss of MSMB in tumour tissue. A subset of the 100 genes outperforms established clinical predictors of poor prognosis (PSA, Gleason score), as well as previously published gene signatures (p = 0.0001). We further show how our molecular profiles can be used for the early detection of aggressive cases in a clinical setting, and inform treatment decisions. INTERPRETATION: For the first time in prostate cancer this study demonstrates the importance of integrated genomic analyses incorporating both benign and tumour tissue data in identifying molecular alterations leading to the generation of robust gene sets that are predictive of clinical outcome in independent patient cohorts.Cambridge work was funded by a CRUK programme grant awarded to DEN; Swedish work and tissue collections were funded by grants from the Linne Centre for Breast and Prostate Cancer (CRISP, grant 70867901), Karolinska Institutet, the Swedish Research Council (K2010-70X-20430-04-3), and the Swedish Cancer Society (11-0287).This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.ebiom.2015.07.01

Integration of copy number and transcriptomics provides risk stratification in prostate cancer : a discovery and validation cohort study

Study data are deposited in NCBI GEO (unique identifier number GSE70770).Background : Understanding the heterogeneous genotypes and phenotypes of prostate cancer is fundamental to improving the way we treat this disease. As yet, there are no validated descriptions of prostate cancer subgroups derived from integrated genomics linked with clinical outcome. Methods : In a study of 482 tumour, benign and germline samples from 259 men with primary prostate cancer, we used integrative analysis of copy number alterations (CNA) and array transcriptomics to identify genomic loci that affect expression levels of mRNA in an expression quantitative trait loci (eQTL) approach, to stratify patients into subgroups that we then associated with future clinical behaviour, and compared with either CNA or transcriptomics alone. Findings : We identified five separate patient subgroups with distinct genomic alterations and expression profiles based on 100 discriminating genes in our separate discovery and validation sets of 125 and 103 men. These subgroups were able to consistently predict biochemical relapse (p = 0.0017 and p = 0.016 respectively) and were further validated in a third cohort with long-term follow-up (p = 0.027). We show the relative contributions of gene expression and copy number data on phenotype, and demonstrate the improved power gained from integrative analyses. We confirm alterations in six genes previously associated with prostate cancer ( MAP3K7, MELK, RCBTB2, ELAC2, TPD52, ZBTB4), and also identify 94 genes not previously linked to prostate cancer progression that would not have been detected using either transcript or copy number data alone. We confirm a number of previously published molecular changes associated with high risk disease, including MYC amplification, and NKX3-1, RB1 and PTEN deletions, as well as over-expression of PCA3 and AMACR, and loss of MSMB in tumour tissue. A subset of the 100 genes outperforms established clinical predictors of poor prognosis (PSA, Gleason score), as well as previously published gene signatures (p = 0.0001). We further show how our molecular profiles can be used for the early detection of aggressive cases in a clinical setting, and inform treatment decisions. Interpretation : For the first time in prostate cancer this study demonstrates the importance of integrated genomic analyses incorporating both benign and tumour tissue data in identifying molecular alterations leading to the generation of robust gene sets that are predictive of clinical outcome in independent patient cohorts.Publisher PDFPeer reviewe

Risk profiles of prostate cancers identified from UK primary care using national referral guidelines

OBJECTIVE: Prostate cancer in the United Kingdom is mainly diagnosed from primary care referrals based on national guidelines published by the Department of Health. Here we investigated the characteristics of cancers detected through the use of these guidelines. METHODS: A prospective two-centre study was established to assess men referred from the primary care based on the UK national guidelines. RESULTS: The overall cancer detection rate was 43% (169 out of 397) with 15% (26 out of 169) of all cancers metastatic at presentation. Amongst 50-69-year-old men these rates were 34% (68 out of 200) and 15% (10 out of 68). Only 21% (25 out of 123) of men with local cancers had low-risk disease. In comparison to a historical cohort from 2001 (n=137) we found no overall differences in rates of metastatic disease, locally advanced tumours, or risk categories. Amongst 50-69-year-old men with local disease, however, we observed an increase in detection of low-risk cancers in a contemporary cohort (P=0.04). This was primarily because of the increased detection of low-stage organ-confined tumours in this group (P=0.02). CONCLUSION: Use of the UK prostate cancer guidelines detects a high proportion of clinically significant cancers. Use of the guidelines does not seem to have led to an overall change in the clinical characteristics of presenting cancers. There may, however, be a specific benefit in detecting more low-risk disease in younger men

Rhodolith Beds Are Major CaCO3 Bio-Factories in the Tropical South West Atlantic

Rhodoliths are nodules of non-geniculate coralline algae that occur in shallow waters (<150 m depth) subjected to episodic disturbance. Rhodolith beds stand with kelp beds, seagrass meadows, and coralline algal reefs as one of the world's four largest macrophyte-dominated benthic communities. Geographic distribution of rhodolith beds is discontinuous, with large concentrations off Japan, Australia and the Gulf of California, as well as in the Mediterranean, North Atlantic, eastern Caribbean and Brazil. Although there are major gaps in terms of seabed habitat mapping, the largest rhodolith beds are purported to occur off Brazil, where these communities are recorded across a wide latitudinal range (2°N - 27°S). To quantify their extent, we carried out an inter-reefal seabed habitat survey on the Abrolhos Shelf (16°50′ - 19°45′S) off eastern Brazil, and confirmed the most expansive and contiguous rhodolith bed in the world, covering about 20,900 km2. Distribution, extent, composition and structure of this bed were assessed with side scan sonar, remotely operated vehicles, and SCUBA. The mean rate of CaCO3 production was estimated from in situ growth assays at 1.07 kg m−2 yr−1, with a total production rate of 0.025 Gt yr−1, comparable to those of the world's largest biogenic CaCO3 deposits. These gigantic rhodolith beds, of areal extent equivalent to the Great Barrier Reef, Australia, are a critical, yet poorly understood component of the tropical South Atlantic Ocean. Based on the relatively high vulnerability of coralline algae to ocean acidification, these beds are likely to experience a profound restructuring in the coming decades