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Prognostic factors in urological malignancies
No full text© 2014 Dr. Shomik SenguptaBACKGROUND:
The management of urologic cancers relies heavily on the implicit or explicit application of prognostic models. This may range from the appropriate selection of diagnostic tests based upon the pre-test probability of a positive finding, to an informed decision on choice of treatment modality or enrolment in suitable clinical trials.
While some prognostic factors such as stage and grade are time-tested, others such as molecular and immunohistochemical markers or surgical approach are new and evolving. Furthermore, the literature abounds with nomograms, models, risk tables or groups which utilize varying combinations of predictor variables to prognosticate on myriad outcomes of interest.
The aim of this body of work was to enhance our understanding of prognostication in urologic malignancies, particularly prostate cancer, renal cancer and urothelial cancer of the bladder, in various clinical settings.
METHODS:
Details of methodology vary – specifics are outlined in the relevant chapters. In general terms, an appropriate study population was defined based upon the hypothesis. Variables of interest were extracted from suitable database and / or clinical records, or assessed in the laboratory. Associations between predictors and outcomes were analysed using univariate and (where suitable) multivariate regression techniques.
PRINCIPAL RESULTS:
• PSA kinetics provide important prognostic information in various clinical settings, including prior to surgical treatment and after hormonal therapy
• A persistently detectable PSA following radical prostatectomy is associated with a greater risk of progression and death, but with a long natural history
• Younger patients with prostate cancer have less aggressive features, but a proportionately greater risk of progression and death despite curative surgical treatment
• Obese patients with prostate cancer have more adverse pathologic features, but similar oncological outcomes compared to those of normal weight
• A positive family history is associated with an increased risk of developing prostate cancer, but similar oncologic outcomes following surgical treatment
• Gleason scoring has evolved over time, with consequent changes in the prognostic implications thereof
• So-called “insignificant” prostate cancer has similar oncological outcomes to low-risk cancers overall, following surgical treatment
• Patient suitability for brachytherapy as a single modality can be judged based on the clinically assessed risk of lymph node or seminal vesicle involvement
• Clinical factors can predict the risk of nodal metastasis, thus allowing the rational selection of patients for pelvic lymphadenectomy at the time of radical prostatectomy
• RALRP is associated with a lower rate of +SM compared to ORP, even after adjusting for known clinical and pathological risk factors
• Renal cancers in solitary kidneys associated with vena caval extension may be treated by nephron-sparing surgery where technically suitable, although a high risk of disease progression and death remains
• The pre-operative erythrocyte sedimentation rate provides independent prognostic information in patients with renal cancer
• Renal lesions with low nephrometry score as measured using the R.E.N.A.L. have a greater likelihood of having benign or indolent histology
• Histologic coagulative tumour necrosis within renal cancers is associated with poorer oncological outcomes after surgical treatment
• Expression of the oncogene c-kit is rare within high-grade or sarcomatoid renal cancers
• Muscle invasive urothelial cancers of the bladder are often infiltrated by profuse numbers of lymphocytes with a variety of phenotypes, although they appear not to impact on the risk of progression or death after surgical treatment
• Peri-operative chemotherapy has been increasing in its use over recent years, and appears to reduce the risk of recurrence after surgical treatment of urothelial cancer of the bladder
CONCLUSIONS:
Many of the findings summarized above have had important implications for practice. For instance:
• PSA kinetics are now in widespread use at various stages of prostate cancer management
• Gleason scores from patients treated some time ago are often re-interpreted according to revised criteri
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
sj-pdf-1-aic-10.1177_0310057X231154017 - Supplemental material for Pass rates of four P2/N95 respirators or filtering facepiece respirators in Australian healthcare providers: A prospective observational study
No full textSupplemental material, sj-pdf-1-aic-10.1177_0310057X231154017 for Pass rates of four P2/N95 respirators or filtering facepiece respirators in Australian healthcare providers: A prospective observational study by Low Caitlin SR Conceptualization Data curation Funding acquisition Investigation Methodology Project administration Writing – original draft Writing – review & editing Ngui Sean Z Data curation Methodology Project administration Writing – review & editing Casey Matthew J Conceptualization Methodology Project administration Resources Writing – review & editing Vuong Chloe Data curation Methodology Project administration Writing – review & editing Afroz Afsana Formal analysis Methodology Writing – review & editing Sengupta Shomik Funding acquisition Methodology Writing – review & editing Weinberg Laurence Conceptualization Methodology Supervision Writing – review & editing in Anaesthesia and Intensive Care</p
sj-pdf-2-aic-10.1177_0310057X231154017 - Supplemental material for Pass rates of four P2/N95 respirators or filtering facepiece respirators in Australian healthcare providers: A prospective observational study
No full textSupplemental material, sj-pdf-2-aic-10.1177_0310057X231154017 for Pass rates of four P2/N95 respirators or filtering facepiece respirators in Australian healthcare providers: A prospective observational study by Low Caitlin SR Conceptualization Data curation Funding acquisition Investigation Methodology Project administration Writing – original draft Writing – review & editing Ngui Sean Z Data curation Methodology Project administration Writing – review & editing Casey Matthew J Conceptualization Methodology Project administration Resources Writing – review & editing Vuong Chloe Data curation Methodology Project administration Writing – review & editing Afroz Afsana Formal analysis Methodology Writing – review & editing Sengupta Shomik Funding acquisition Methodology Writing – review & editing Weinberg Laurence Conceptualization Methodology Supervision Writing – review & editing in Anaesthesia and Intensive Care</p
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Role of pelvic lymph node dissection in bladder cancer:Is it better to do more?
Full text linkRadical cystectomy (RC) is frequently used for the treatment of muscle invasive bladder cancer (MIBC) (1). Typically, this is accompanied by a pelvic lymph node dissection (PLND), which certainly allows for accurate nodal staging (2) and may even have therapeutic effect, especially in those with small volume disease (3). This has to be weighed against the drawbacks of PLND including increased operative time and added risks of surgery. The decision-making on PLND for MIBC is further complicated by a lack of high-level evidence (4). A systematic review of the available retrospective series suggested a survival benefit to performing PLND, but found the evidence for a greater extent of dissection to be equivocal (5). Thus, although PLND with RC is recommended by guidelines (6), the optimal extent of PLND for MIBC remains uncertain (4,7). The LEA AUO AB 25/02 study by Gschwend et al. is a multi-centre phase-III randomised controlled trial aiming to assess whether extending the PLND improves recurrence-free survival (RFS) (8). This prospective trial was conducted between 2006 and 2010 at 16 high volume RC centres in Germany. Patients were included if they had locally resectable T1 or MIBC. Those with bony or visceral metastases on staging computed tomography as well as those who underwent neoadjuvant chemotherapy were excluded. The primary outcome was 5-year RFS with secondary outcomes including 5-year overall survival (OS), 5-year cancer specific survival (CSS) and post-operative complications. Overall, 401 of 458 potential patients were randomised to undergo either extended or limited PLND with RC. It should be noted that the nomenclature of PLND templates often varies between studies, thus further complicating interpretation of the literature. Thus, what is described as a limited PLND in this study can also be considered a standard PLND (obturator, internal and external iliac groups), whereas the extended PLND study group might be better described as having undergone a super-extended PLND to distinguish from an extended PLND that terminates at the aortic bifurcation (4,6). The trial found no statistically significant differences in the primary endpoint of 5-year RFS (64.6% vs. 59.2%), or secondary endpoints of 5-year CSS (75.9% vs. 64.5%) and 5-year OS (58.9% vs. 49.7%) between extended and limited PLND (8). These findings appear to suggest that there is no oncological benefit to performing a more extensive PLND with RC for MIBC, but need to be interpreted cautiously. Although the study was powered on the assumption of a 5-year RFS of 50% in the limited PLND group, the actual survival was much better at 59%. This may be a consequence of including patients with T1 disease (12% in the limited and 16% in the extended PLND group), who have a low risk of node positive disease. Meta-analysis of previous retrospective studies suggests that the improvement in RFS from extending the PLND may be seen only in patients with T3 to 4 bladder cancer, not in those with stage T2 or lower (9). There have been a number of studies that suggest improved recurrence free survival in those patients who have more lymph nodes removed at PLND (10,11). In the study by Gschwend et al., the median number of lymph nodes removed was 19 in the limited PLND group and 31 in the extended PLND group (8). This is quite high in both groups, but more in those that underwent extended PLND, as might be expected. However, this did not result in a higher rate of node positivity, as is usually seen with a more extensive PLND (9). Possible explanatory factors may include a high number of lymph nodes removed even in the limited PLND group and an imbalance in T-stage between the two groups, given that there were slightly more patients with T1 disease and less patients with T4 disease in the extended PLND group. To what extent this might have also contributed to the lack of impact of extended PLND on RFS is unclear. Interestingly, although there was no difference between the two groups in terms of node-positivity, within the extended PLND group, 21 (11%) had positive nodes within the extended field of dissection, including 4 (2%) in whom the limited PLND fields were negative. Thus, an understanding of which sites are likely to be involved is also important in determining what extent of PLND is required. Leissner and colleagues demonstrated that the majority of nodal metastases occurred in the obturator spaces and adjacent to the iliac vessels, while metastases in the inter-aorto-caval and paracaval regions were far less likely (12). Conversely, a number of studies have also confirmed that a substantial proportion of metastatic lymph node deposits are outside the boundaries defining the limited PLND in the AUO trial (12-14). Thus, it may be concluded that the optimal PLND template should lie somewhere between those defined as limited and extended in this trial, i.e., extending up to the aortic bifurcation. Of course, PLND is not without risk, specifically including lymphoceles formation, vascular injury and thrombo-embolic sequelae (4,7). Increasing the extent of PLND raises the concern of potentially increasing these risks. Reassuringly, the AUO study found comparable rates of major morbidity and mortality between the two groups, with the only difference being a higher rate of lymphoceles requiring intervention in the extended compared to the standard PLND group (8.6% vs. 3.4%, P=0.04) (8). An interesting secondary analysis in this study relates to the use of adjuvant chemotherapy (AC), in the form of 4 cycles of Gemcitabine and Cisplatin, delivered at physician discretion. Only 58 patients received AC, being 14.5% of the overall study population, but 28% of the 205 patients with high-risk pathology (T3 and 4 or node-positive), who were principally considered for treatment. The impact of AC, assessed as a prespecified secondary endpoint in this subgroup, was to improve median RFS from 11.5 to 35.4 months (hazard ratio 0.56, 95% CI: 0.38–0.83; P=0.004). Although this finding needs to be interpreted with caution, based as it is on a non-randomised comparison, it adds support to the evidence that AC after RC may improve outcomes for bladder cancer (15). Overall Gschwend et al. should be congratulated on their study—surgical trials are notoriously difficult to accrue. The standardisation of PLND templates and the thorough dissection evidenced by high lymph node yields in both groups are particular strengths of the study. The inclusion of patients with T1 disease, the exclusion of neo-adjuvant and low use of adjuvant chemotherapy represent some limitations. Further research is required to address the interaction of peri-operative chemotherapy with PLND and determining how the extent of PLND can be optimised. The SWOG 1011 trial is another large randomised controlled trial currently underway in multiple centres in the United States, comparing extended vs. standard PLND with RC for MIBC with the primary outcome being disease-free survival and secondary outcomes including lymph node counts, operative time and OS (16). Accrual is planned for 620 participants and expected to be completed in August 2022—results from this study will be crucial to further inform the surgical management of MIBC
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