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Article of the week: A transcriptomic signature of tertiary Gleason 5 predicts worse clinicopathological outcome

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Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an editorial written by a prominent member of the urological community, and a video produced by the authors. These are intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation. 

If you only have time to read one article this week, it should be this one.

A transcriptomic signature of tertiary Gleason 5 predicts worse clinicopathological outcome

Alberto Martini*, Joanna Wang*, Nicholas M. Brown*, Shivaram Cumarasamy*, John P. Sfakianos*, Ardeshir R. Rastinehad*, Kenneth G. Haines III†, Nils Peter Wiklund*, Sujit S. Nair* and Ashutosh K. Tewari*

 

Departments of *Urology and †Pathology, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, USA

 

Abstract

Objective

To investigate the genomic features of tertiary pattern 5 (TP5) on radical prostatectomy specimens in an effort to explain the poor clinical outcomes associated with this disease subtype.

Patients and methods

Data from 159 men with Gleason Grade Group (GGG) 3 or 4 were considered. All patients had Decipher diagnostic testing with transcript profiles and single‐channel array normalisation (SCAN)‐normalised expression of coding genes.

The relationship between Decipher and TP5 was investigated by linear and binary logistic regressions. A differential transcriptomic analysis between patients with and without TP5 was performed. The prognostic role of these genes on progression‐free survival (PFS) and overall survival (OS) was evaluated using The Cancer Genome Atlas.

Results

In all, 52/159 (33%) patients had GGG 3–4 with TP5 disease. TP5 was associated with a higher Decipher score (β 0.07, 95% confidence interval [CI] 0.02–0.13; P = 0.04) and higher likelihood of falling within the intermediate‐ or high‐risk categories (odds ratio 3.34, 95% CI 1.34–8.35; P = 0.01). Analysis of microarray data revealed an 18‐gene signature that was differentially expressed in patients with TP5; 13 genes were over‐ and five under‐expressed in the TP5 cohort.

The overexpression of cyclin dependent kinase inhibitor 2B (CDKN2B), polo‐like kinase 1 (PLK1), or cell division cycle 20 (CDC20) was associated with worse PFS. The group harbouring overexpression of at least one gene had a 5‐year PFS rate of 50% vs 74% in the group without overexpression (P < 0.001).

Conclusions

Our studies have elucidated unique genomic features of TP5, whilst confirming previous clinical findings that patients harbouring TP5 tend to have worse prognosis. This is the first RNA‐based study to investigate the molecular diversity of TP5 and the first correlating CDKN2B to poorer prognosis in patients with prostate cancer.

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Editorial: Transcriptomic signatures for tertiary pattern 5 in prostate cancer

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Significant evidence is now emerging and publications have shown that the molecular characterization of tumours represents an important approach to stratifying patients with prostate cancer into appropriate treatments and their responses, helping to inform the next steps in the care pathway of these patients [1]. Understanding the functional role of the genes included in these signatures also gives an insight into the biology of the disease and how it develops and progresses.

BJUI has published papers in the past describing gene signatures that are associated with pathological Gleason score as pathological markers of aggressiveness and their potential role in predicting outcome [2].

The paper by Martini et al. [3] in the current issue of BJUI adds to this important literature. In a cohort of 159 patients, of whom 52 had tertiary pattern 5 (TP5) prostate cancer, Martini et al. showed that TP5 was associated with higher risk categories in the Decipher genomic score. Their study supports the literature showing that patients with TP5 have an elevated likelihood of developing disease after radical prostatectomy and have a poor prognosis [4]. It should be noted, however, that this is a small cohort with few patients defined as having TP5 disease. As prostate cancer is highly heterogeneous and gene expression can also be affected by the patient’s background, additional validation of this finding will be required in independent cohorts.

Additional analysis of the 698 gene by Martini et al. [3] identified a unique RNA signature of 18 genes for the TP5 cohort. A limitation of using the 698 gene previously demonstrated to be related to prostate cancer is that those with TP5 disease may be a unique subset of patients that may be associated with unfamiliar pathological pathways and new genes. An examination of novel genes whose expression pattern is unique to patients with TP5 disease may reveal additional genes.

Martini et al. then used the independent TCGA provisional database to link the expression of these 18 genes with clinical features. Patients harbouring any of the three genes CDKN2B, PLK1 and CDC20 mRNA were found to have worse progression‐free survival. The authors go on to undertake analysis of the 18 genes using the ingenuity network analysis tool identifying pathways involved in the cell cycle, DNA replication and repair, cellular assembly, cell death and survival and gene expression, which would fit with the biology of progressive disease. They also revealed a role in the dedifferentiation process and progression of cells towards anaplasia. They specifically identified CDKN2B, which has previously been associated with tumour suppression but might actually be linked to tumour progression, and identified it for further investigation.

Finally the researchers found that 13 genes out of the 18‐gene TP5 signature are upregulated in tumour lesions with TP5. Following these results they performed a sensitivity analysis in which the expression values of the genes in the cohort with GGG3‐4 and TP5 were compared with those of patients with GGG5 and discovered that these genes were similarly overexpressed in both groups. This finding strengthens the hypothesis that these genes are implicated in the dedifferentiation process of tumour cells, but it also raises the question of whether the pattern of expression of these genes is unique to patients with TP5 only, or whether it is associated with every tumour (primary, secondary or tertiary) that is classified as GGG5. Further research is needed to understand what the clinical significance of this genetic signature is and what pathological process it describes in practice.

This investigation into the functional role of the genes has given an insight into the biology of prostate cancer progression and TP5 disease which might inform a future area of research for novel biomarker panels and therapeutic interventions.

by R. William Watson and Omri Taltsh

References

  1. Cucchiara, V, Cooperberg, MR, Dall’Era, M, Lin, DW, Montorsi, F, Schalken, JA, Evans, CP Genomic markers in prostate cancer decision making. Euro Urol 2018; 73: 572– 82
  2. Pellegrini, K, Sanda, MG, Patil, D, Long, Q, Santiago‐Jiménez, M, Takhar, M, Erho, N, Yousefi, K,Davicioni, E, Klein, EA, Jenkins, RB, Karnes, RJ, Moreno, CS Evaluation of a 24‐Gene signature for prognosis of metastatic events and prostate cancer‐specific mortality. BJU Int 2017; 119: 961– 7
  3. Martini, A, Wang, J, Brown, NM, Cumarasamy, S, Sfakianos, JP, Rastinehad, AR, Haines, KG,Wiklund, NP, Nair, SS, Tewari, AK A transcriptomic signature of tertiary Gleason 5 predicts worse clinicopathological outcome. BJU Int 2019; 124: 155– 62
  4. Whittemore, DE, Hick, EJ, Carter, MR, Moul, JW, Miranda‐Sousa, AJ, Sexton, WJ Significance of tertiary Gleason pattern 5 in Gleason score 7 radical prostatectomy specimens. J Urol 2008; 179:516– 22

 

 

Editorial: Preoperative PSMA‐targeted PET imaging: more than just a tool for prostate cancer staging?

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The presence of lymph node metastases at the time of prostate cancer diagnosis has significant implications for treatment. According to current guidelines from the National Comprehensive Cancer Network, men with positive lymph nodes on initial staging imaging should be offered treatment with androgen deprivation (± abiraterone) along with consideration for external beam radiation therapy [1]. In contrast, men with clinically localised high‐ or very‐high‐risk prostate cancer have the option of undergoing radical prostatectomy. Unfortunately, currently available diagnostic imaging modalities (i.e. contrast‐enhanced CT and MRI) fall short in their ability to accurately identify lymph node metastases, which are often small and difficult to discern from other structures within the pelvis. Thus, there exists a conundrum: if we cannot accurately detect lymph node involvement, how can we appropriately manage it?

In this edition of the BJUI, Leeuwen et al. [2] report on the utility of molecular imaging with 68Ga‐PSMA‐11 positron emission tomography (PET)/CT in the preoperative staging of men with prostate cancer. To date, the greatest clinical utility of PSMA‐targeted PET has been in the management of men with biochemically recurrent prostate cancer [3]. In the present study by Leeuwen et al. [2], 140 patients with newly diagnosed intermediate‐ or high‐ risk prostate cancer underwent 68Ga‐PSMA‐11 PET/CT before radical prostatectomy with extended pelvic lymph node dissection. Surgical pathology served as the reference standard to which findings on 68Ga‐PSMA‐11 PET/CT were compared. In total, 27.1% of men were found to have radiotracer uptake in their pelvic lymph nodes, resulting in a sensitivity of 53% and a specificity of 88%. In contrast, multiparametric MRI had a sensitivity of only 14%, albeit with a higher specificity of 99%. These findings are in line with prior studies evaluating the diagnostic performance of PSMA‐targeted PET imaging for preoperative prostate cancer staging [4]. Of greater interest, however, is the authors’ observation that positivity on 68Ga‐PSMA‐11 PET/CT was strongly associated with postoperative PSA persistence (i.e. failure to cure). More specifically, after controlling for Gleason score, surgical margin status, and preoperative PSA level, positivity on PET/CT had an odds ratio of 5.87 (95% CI 1.30–26.59) for biochemical persistence. Furthermore, men with pN1 disease and a positive preoperative PET/CT (i.e. true positives) were over three times more likely to experience biochemical persistence than patients with pN1 disease and negative imaging (71.4% vs 21.4%). Thus, PSMA‐targeted PET not only stands to inform clinical staging, but also has the potential to offer independent prognostic information.

A future line of investigation is to explore the biological basis of the authors’ observation regarding PSMA as a prognostic marker. One explanation is that PET/CT identified men with higher volume lymph node metastases (a known prognostic factor), whilst patients with smaller more curable nodes were negative on imaging. After all, the authors state that the imaging test did not detect any pathologically positive lymph nodes <2 mm. Furthermore, only 27% of positive lymph nodes between 2 and 4 mm showed radiotracer uptake. Unfortunately, the authors did not account for differences in the volume of nodal metastases in their analysis. A second possible explanation for the authors’ observation is that PSMA is upregulated through the same signaling pathways that drive an aggressive prostate cancer phenotype, allowing for PSMA expression to provide prognostic information independent of tumour volume. Indeed, others have previously shown that PSMA expression, as measured by immunohistochemistry, corresponds with increasing tumour grade, stage and risk of biochemical failure [5]. Of course, these concepts are not mutually exclusive and further investigation is needed in order for PSMA‐targeted imaging to be rationally applied as a prognostic test.

References

  1. NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer (Version 4.2018). 2018. Accessed November 2018. Available at: https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf.
  2. Leeuwen, PJ, Donswijk, M, Nandurkar, R et al. Gallium‐68‐prostate‐specific membrane antigen (68Ga‐PSMA) positron emission tomography (PET)/computed tomography (CT) predicts complete biochemical response from radical prostatectomy and lymph node dissection in intermediate‐ and high‐risk prostate cancer. BJU Int 2019; 124: 62– 8
  3. Han, S, Woo, S, Kim, YJ, Suh, CH. Impact of 68Ga‐PSMA PET on the management of patients with prostate cancer: a systematic review and meta‐analysis. Eur Urol 2018; 74: 179– 90
  4. Gorin, MA, Rowe, SP, Patel, HD et al. Prostate specific membrane antigen targeted 18F‐DCFPyL positron emission tomography/computerized tomography for the preoperative staging of high risk prostate cancer: results of a prospective, phase II, single center study. J Urol 2018; 199: 126– 32
  5. Minner, S, Wittmer, C, Graefen, M et al. High level PSMA expression is associated with early PSA recurrence in surgically treated prostate cancer. Prostate 2011; 71: 281– 8

 

Article of the week: Examining the relationship between complications and perioperative mortality following radical cystectomy: a population‐based analysis

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Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an editorial written by a prominent member of the urological community. These are intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation. 

If you only have time to read one article this month, it should be this one.

Examining the relationship between complications and perioperative mortality following radical cystectomy: a population‐based analysis

Matthew Mossanen*†‡, Ross E. Krasnow§, Dimitar V. Zlatev*, Wei Shen Tan**, Mark A. Preston*†, Quoc-Dien Trinh*†‡, Adam S. Kibel*†, Guru Sonpavde†, Deborah Schrag†, Benjamin I. Chung†† and Steven L. Chang*†††

*Division of Urology, Harvard Medical School, Brigham and Women’s Hospital, †Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, ‡Center for Surgery and Public Health, Brigham and Women’s Hospital, Boston, MA, Division of Surgery and Interventional Sciences, Department of Urology, University College London, **Department of Urology, Imperial College Healthcare, London, UK, §Department of Urology, Georgetown University, Washington, DC, USA and ††Department of Urology, Stanford University Medical Center, Stanford, CA, USA
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Abstract

Objective

To examine the incidence of perioperative complications after radical cystectomy (RC) and assess their impact on 90‐day postoperative mortality during the index stay and upon readmission.

Patients and methods

A total of 57 553 patients with bladder cancer (unweighted cohort: 9137 patients) treated with RC, at 360 hospitals in the USA between 2005 and 2013 within the Premier Healthcare Database, were used for analysis. The 90‐day perioperative mortality was the primary outcome. Multivariable regression was used to predict the probability of mortality; models were adjusted for patient, hospital, and surgical characteristics.

Results

An increase in the number of complications resulted in an increasing predicted probability of mortality, with a precipitous increase if patients had four or more complications compared to one complication during hospitalisation following RC (index stay; 1.0–9.7%, P < 0.001) and during readmission (2.0–13.1%, P < 0.001). A readmission complication nearly doubled the predicted probability of postoperative mortality as compared to an initial complication (3.9% vs 7.4%, P < 0.001). During the initial hospitalisation cardiac‐ (odds ratio [OR] 3.1, 95% confidence interval [CI] 1.9–5.1), pulmonary‐ (OR 4.8, 95% CI 2.8–8.4), and renal‐related (OR 3.6, 95% CI 2–6.7) complications had the most significant impact on the odds of mortality across categories examined.

Conclusions

The number and nature of complications have a distinct impact on mortality after RC. As complications increase there is an associated increase in perioperative mortality.

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Article of the week: Suture techniques during laparoscopic and robot‐assisted partial nephrectomy

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Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is a video produced by the authors. Please use the tools at the bottom of the post if you would like to make a comment. 

If you only have time to read one article this week, it should be this one.

Suture techniques during laparoscopic and robot‐assisted partial nephrectomy: a systematic review and quantitative synthesis of peri‐operative outcomes

Riccardo Bertolo*, Riccardo Campi†, Tobias Klatte‡, Maximilian C. Kriegmair§, Maria Carmen Mir, Idir Ouzaid**, Maciej Salagierski††, Sam Bhayani‡‡, Inderbir Gill§§¶¶, Jihad Kaouk* and Umberto Capitanio‡‡§§***††† On behalf of the Young Academic Urologists (YAU) Kidney Cancer working group of the European Urological Association (EAU)

 

*Department of Urology, Cleveland Clinic Foundation, Cleveland, OH, USA, †Department of Urology, University of Florence, Florence, Italy, ‡Department of Urology, Royal Bournemouth and Christchurch Hospitals, Bournemouth, UK, §Department of Urology, University Medical Centre Mannheim, Mannheim, Germany, Department of Urology, Fundación Instituto Valenciano de Oncología, Valencia, Spain, **Department of Urology, Bichat Hospital, APHP, Paris Diderot University, Paris, France, ††Urology Department, Faculty of Medicine and Health Sciences, University of Zielona Góra, Zielona Góra, Poland, ‡‡Division of Urology, Washington University School of Medicine, St Louis, MO, §§Keck School of Medicine, USC Institute of Urology, ¶¶Catherine and Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA, ***Department of Urology, San Raffaele Scientific Institute, and †††Division of Experimental Oncology/Unit of Urology, URI, IRCCS San Raffaele Hospital, Milan, Italy

 

Read the full article

Abstract

Objective

To summarize the available evidence on renorrhaphy techniques and to assess their impact on peri‐operative outcomes after minimally invasive partial nephrectomy (MIPN).

Materials and Methods

A systematic review of the literature was performed in January 2018 without time restrictions, using MEDLINE, Cochrane and Web of Science databases according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement recommendations. Studies providing sufficient details on renorrhaphy techniques during laparoscopic or robot‐assisted partial nephrectomy and comparative studies focused on peri‐operative outcomes were included in qualitative and quantitative analyses, respectively.

Fig. 4. Integrated overview of evidence‐based technical principles for renal reconstruction during minimally invasive partial nephrectomy and suggested standardized reporting of key renorrhaphy features in clinical studies on this topic.

Results

Overall, 67 and 19 studies were included in the qualitative and quantitative analyses, respectively. The overall quality of evidence was low. Specific tumour features (i.e. size, hilar location, anatomical complexity, nearness to renal sinus and/or urinary collecting system), surgeon’s experience, robot‐assisted technology, as well as the aim of reducing warm ischaemia time and the amount of devascularized renal parenchyma preserved represented the key factors driving the evolution of the renorrhaphy techniques during MIPN over the past decade. Quantitative synthesis showed that running suture was associated with shorter operating and ischaemia time, and lower postoperative complication and transfusion rates than interrupted suture. Barbed suture had lower operating and ischaemia time and less blood loss than non‐barbed suture. The single‐layer suture technique was associated with shorter operating and ischaemia time than the double‐layer technique. No comparisons were possible concerning renal functional outcomes because of non‐homogeneous data reporting.

Conclusions

Renorrhaphy techniques significantly evolved over the years, improving outcomes. Running suture, particularly using barbed wires, shortened the operating and ischaemia times. A further advantage could derive from avoiding a double‐layer suture.

 

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Video: Suture techniques during laparoscopic and robot‐assisted partial nephrectomy

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Suture techniques during laparoscopic and robot‐assisted partial nephrectomy: a systematic review and quantitative synthesis of peri‐operative outcomes

by Riccardo Bertolo (@RicBertolo)

Read the full article

Abstract

Objective

To summarize the available evidence on renorrhaphy techniques and to assess their impact on peri‐operative outcomes after minimally invasive partial nephrectomy (MIPN).

Materials and Methods

A systematic review of the literature was performed in January 2018 without time restrictions, using MEDLINE, Cochrane and Web of Science databases according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement recommendations. Studies providing sufficient details on renorrhaphy techniques during laparoscopic or robot‐assisted partial nephrectomy and comparative studies focused on peri‐operative outcomes were included in qualitative and quantitative analyses, respectively.

Results

Overall, 67 and 19 studies were included in the qualitative and quantitative analyses, respectively. The overall quality of evidence was low. Specific tumour features (i.e. size, hilar location, anatomical complexity, nearness to renal sinus and/or urinary collecting system), surgeon’s experience, robot‐assisted technology, as well as the aim of reducing warm ischaemia time and the amount of devascularized renal parenchyma preserved represented the key factors driving the evolution of the renorrhaphy techniques during MIPN over the past decade. Quantitative synthesis showed that running suture was associated with shorter operating and ischaemia time, and lower postoperative complication and transfusion rates than interrupted suture. Barbed suture had lower operating and ischaemia time and less blood loss than non‐barbed suture. The single‐layer suture technique was associated with shorter operating and ischaemia time than the double‐layer technique. No comparisons were possible concerning renal functional outcomes because of non‐homogeneous data reporting.

Conclusions

Renorrhaphy techniques significantly evolved over the years, improving outcomes. Running suture, particularly using barbed wires, shortened the operating and ischaemia times. A further advantage could derive from avoiding a double‐layer suture.

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Visual abstract: Early and rapid prediction of postoperative infections following percutaneous nephrolithotomy in patients with complex kidney stones

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Article of the week: Early and rapid prediction of postoperative infections following PCNL in patients with complex kidney stones

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Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an editorial  and a visual abstract prepared by prominent members of the urological community. These are intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation. 

If you only have time to read one article this week, it should be this one.

Early and rapid prediction of postoperative infections following percutaneous nephrolithotomy in patients with complex kidney stones

Dong Chen*, Chonghe Jiang†, Xiongfa Liang*, Fangling Zhong*, Jian Huang*, Yongping Lin‡, Zhijian Zhao*, Xiaolu Duan*, Guohua Zeng* and Wenqi Wu*

 

*Department of Urology, Guangdong Key Laboratory of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, †Department of Urology, The People’s Hospital of Qingyuan City, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan, and ‡Department of Laboratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China

 

Read the full article

Abstract

Objectives

To obtain more accurate and rapid predictors of postoperative infections following percutaneous nephrolithotomy (PCNL) in patients with complex kidney stones, and provide evidence for early prevention and treatment of postoperative infections.

Patients and Methods

A total of 802 patients with complex kidney stones who underwent PCNL, from September 2016 to September 2017, were recruited. Urine tests, urine cultures (UCs) and stone cultures (SCs) were performed, and the perioperative data were prospectively recorded.

Results

In all, 19 (2.4%) patients developed postoperative urosepsis. A multivariate logistic regression analysis revealed that an operating time of ≥100 min, urine test results with both positive urine white blood cells (WBC+) and positive urine nitrite (WBC+NIT+), positive UCs (UC+), and positive SCs (SC+) were independent risk factors of urosepsis. The incidence of postoperative urosepsis was higher in patients with WBC+NIT+ (10%) or patients with both UC+ and SC+ (UC+SC+; 8.3%) than in patients with negative urine test results or negative cultures (P < 0.01). Preoperative WBC+NIT+ was predictive of UC+SC+, with an accuracy of >90%. The main pathogens found in kidney stones were Escherichia coli (44%), Proteus mirabilis (14%) and Staphylococcus (7.4%); whilst the main pathogens found in urine were E. coli (54%), Enterococcus (9.4%) and P. mirabilis (7.6%). The incidence of E. coli was more frequent in the group with urosepsis than in the group without urosepsis (P < 0.05).

Conclusions

WBC+NIT+ in preoperative urine tests could be considered as an early and rapid predictor of UC+SC+ and postoperative urosepsis. Urosepsis following PCNL was strongly associated with E. coli infections in patients with complex kidney stones.

 

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Editorial: Predicting sepsis after percutaneous nephrolithotomy

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In this month’s BJUI, Chen et al. [1] report on a large series of percutaneous nephrolithotomy (PCNL) procedures from Guangzhou in China. The authors studied patients who developed postoperative urosepsis and looked for any predictive factors that would herald impending sepsis.

In this latest report, the authors analysed 802 patients with complex kidney stones undergoing PCNL in a single centre. ‘Complex’ was defined as complete staghorn, partial staghorn or pelvic stone with at least two calyceal stones. Midstream urines (MSU) were collected and analysed for white blood cells (WBC) and nitrites (NIT). Antibiotics were given preoperatively if the urine culture (UC) was positive for WBC (WBC+) or NIT (NIT+). Standard single‐dose antibiotic was given on induction of anaesthesia and only continued for 48 h if the culture was positive. Stone cultures (SCs) were routinely collected. Of the 802 patients, UCs were positive (UC+) in 171 (21%) and SCs subsequently positive (SC+) in 30%. Postoperatively, 98 (12%) developed a fever, 62 (7.7%) developed systemic inflammatory response syndrome (SIRS), and 19 (2.4%) developed sepsis as defined by the quick Sequential (sepsis‐related) Organ Failure Assessment (qSOFA).

Multiple factors were significantly associated with sepsis: female sex (79% vs 40%), infection stone (47% vs 21%), long operating time ≥100 min (74% vs 45%), multiple accesses (32% vs 10%), UC+ (63% vs 20%), SC+ (89% vs 29%), fever (74% vs 11%), as well as being both WBC+ and NIT+ (63% vs 13%). Conversely, if WBC and NIT were negative (WBC–NIT–) the risk of sepsis was only 5.3%. On multivariate analysis SC+ (odds ratio [OR] 8.0), operating time ≥100 min (OR 4.4), WBC+ and NIT+ (OR 3.9), UC+ (OR 3.2), were independent risk factors for sepsis. Not surprisingly having UC+, SC+ or both showed a statistically higher incidence of fever, SIRS, and sepsis. Being WBC+ and NIT+ was the best predictor of having both UC+ and SC+ with an impressive 92% sensitivity and 98% specificity.* Similarly, WBC+ and NIT+ was the best predictor of sepsis with 92% sensitivity and 82% specificity. The absolute risk of sepsis was only 0.2% if WBC–NIT–, 2.8% if only one was positive, and 10% if WBC+NIT+.

The authors also report on the bacterial findings of the UCs and SCs. In the SCs, Escherichia coli (44%), Proteus mirabilis (14%) and Staphylococcus (7.4%) were the most common; whilst in the UCs, E. coli (54%), Enterococcus (9.4%) and P. mirabilis (7.6%) were predominant. It is important to remember the potential differences when interpreting UCs preoperatively and to ensure broad‐spectrum cover is given and this justifies the sending of SCs, particularly in high‐risk patients [1].

The recognition of early sepsis is paramount and has been recognised in previous studies leading to the ‘golden hour’, when early aggressive treatment of the infection has been shown to lead to better outcomes [2]. In a large study by Kumar et al. [2], early antimicrobial administration (within the first hour of hypotension from septic shock) led to a higher overall survival; but worryingly, only 50% of patients received appropriate antibiotics within 6 h. Thus, if high‐risk patients could be predicted then closer monitoring, aggressive fluid management, and early broad‐spectrum antibiotics with intensive care support could be targeted at those specific patients.

There are multiple definitions for infection, e.g., sepsis, severe sepsis, septic shock, and SIRS. The 2016 International Consensus attempted to clarify these and defined sepsis as ‘A life‐threatening organ dysfunction due to dysregulated host response to infection’ [3]. They found the term ‘severe sepsis’ to be obsolete. Septic shock is defined as ‘a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone’ [3]. The Consensus recommended organ dysfunction is assessed by a SOFA score increase of ≥2, as this is associated with a mortality of 10%. This then led to the bedside assessment clinical score called qSOFA. Poorer outcomes were associated with two or more of the qSOFA criteria: respiratory rate ≥22 breaths/min, altered mentation (as judged by the Glasgow Coma Scale), and systolic blood pressure ≤100 mmHg.

In this current study [1], many of the factors associated with postoperative sepsis are logical and have been demonstrated before, e.g., female sex, infection stone, prolonged operating times, and multiple accesses. This paper has shown that careful attention to the preoperative urine dipstick can provide important prediction of potential severe infective complications postoperatively. In an era of antibiotic stewardship this could help guide targeted preoperative and prolonged postoperative antibiotics for a small group of patients, whilst managing WBC–NIT– patients with standard prophylaxis only. The high‐risk group should also be observed very closely postoperatively and moved to a high‐dependence setting rapidly if clinical signs of sepsis develop. It would also suggest that in this high‐risk group, operating times and intra‐renal pressure should be minimised. It may be that in these patients it is better to use larger tract PCNL sizes to allow rapid fragmentation and evacuation of the stone and that consideration should be given to staged procedures in complicated stones where multiple access is being considered to minimise operating time and allow analysis of intraoperative SCs.

It should of course be remembered that antibiotic decisions should be based on local policies and sensitivities, which may be very different from this population. Rapid treatment of sepsis is paramount and the most recent ‘Hour‐1’ bundle provides the most up‐to‐date guidance for immediate resuscitation and management with lactate management, blood cultures, broad‐spectrum antibiotics, i.v. fluids, and early use of vasopressors if the blood pressure does not respond to fluid replacement [4].

by Matt Bultitude and Kay Thomas

References

  1. Chen, D, Jiang, C, Liang, X et al. Early and rapid prediction for postoperative infections following percutaneous nephrolithotomy in patients with complex kidney stones. BJU Int 2019; 123: 1041– 7
  2. Kumar, A, Roberts, D, Wood, KE et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006; 34: 1589– 96
  3. Singer, M, Deutschman, CS, Seymour, CW et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis‐3). JAMA 2016; 315: 801– 10
  4. Levy, MM, Evans, LE, Rhodes, A. The surviving sepsis campaign bundle: 2018 update. Crit Care Med 2018; 46: 997– 1000

*FileS1; FileS2

 

Article of the week: Palliative care use amongst patients with bladder cancer

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Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an editorial written by a prominent member of the urological community, a video produced by the authors and a visual abstract created by Charles Scott and Nurhan Abbud. These are intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation. 

If you only have time to read one article this week, it should be this one.

Palliative care use among patients with bladder cancer

Lee A. Hugar*, Samia H. Lopa*, Jonathan G. Yabes†, Justin A. Yu‡, Robert M. Turner II*, Mina M. Fam*, Liam C. MacLeod*, Benjamin J. Davies*, Angela B. Smith§¶ and Bruce L. Jacobs*

 

*Department of Urology, †Department of Medicine, ‡Department of Medicine, Section of Palliative Care and Medical Ethics, University of Pittsburgh School of Medicine, Pittsburgh, PA, §Department of Urology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

 

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Abstract

Objectives

To describe the rate and determinants of palliative care use amongst Medicare beneficiaries with bladder cancer and encourage a national dialogue on improving coordinated urological, oncological, and palliative care in patients with genitourinary malignancies.

Patients and methods

Using Surveillance, Epidemiology, and End Results‐Medicare data, we identified patients diagnosed with muscle‐invasive bladder cancer (MIBC) between 2008 and 2013. Our primary outcome was receipt of palliative care, defined as the presence of a claim submitted by a Hospice and Palliative Medicine subspecialist. We examined determinants of palliative care use using logistic regression analysis.

Fig. 1. Time from diagnosis to receipt of palliative care. The timing of palliative care receipt for those patients who received palliative care (n = 262). Strata with <11 patients were suppressed in accordance with SEER‐Medicare guidelines

Results

Over the study period, 7303 patients were diagnosed with MIBC and 262 (3.6%) received palliative care. Of 2185 patients with advanced bladder cancer, defined as either T4, N+, or M+ disease, 90 (4.1%) received palliative care. Most patients that received palliative care (>80%, >210/262) did so within 24 months of diagnosis. On multivariable analysis, patients receiving palliative care were more likely to be younger, female, have greater comorbidity, live in the central USA, and have undergone radical cystectomy as opposed to a bladder‐sparing approach. The adjusted probability of receiving palliative care did not significantly change over time.

Conclusions

Palliative care provides a host of benefits for patients with cancer, including improved spirituality, decrease in disease‐specific symptoms, and better functional status. However, despite strong evidence for incorporating palliative care into standard oncological care, use in patients with bladder cancer is low at 4%. This study provides a conservative baseline estimate of current palliative care use and should serve as a foundation to further investigate physician‐, patient‐, and system‐level barriers to this care.

 

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