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Video: Biparametric vs multiparametric prostate MRI for the detection of PCa in treatment‐naïve patients: a diagnostic test accuracy systematic review and meta‐analysis

Abstract

Objective

To perform a diagnostic test accuracy (DTA) systematic review and meta‐analysis comparing multiparametric (diffusion‐weighted imaging [DWI], T2‐weighted imaging [T2WI], and dynamic contrast‐enhanced [DCE] imaging) magnetic resonance imaging (mpMRI) and biparametric (DWI and T2WI) MRI (bpMRI) in detecting prostate cancer in treatment‐naïve patients.

Methods

The Medical Literature Analysis and Retrieval System Online (MEDLINE) and Excerpta Medica dataBASE (EMBASE) were searched to identify relevant studies published after 1 January 2012. Articles underwent title, abstract, and full‐text screening. Inclusion criteria consisted of patients with suspected prostate cancer, bpMRI and/or mpMRI as the index test(s), histopathology as the reference standard, and a DTA outcome measure. Methodological and DTA data were extracted. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)‐2 tool. DTA metrics were pooled using bivariate random‐effects meta‐analysis. Subgroup analysis was conducted to assess for heterogeneity.

Results

From an initial 3502 studies, 31 studies reporting on 9480 patients (4296 with prostate cancer) met the inclusion criteria for the meta‐analysis; 25 studies reported on mpMRI (7000 patients, 2954 with prostate cancer) and 12 studies reported on bpMRI DTA (2716 patients, 1477 with prostate cancer). Pooled summary statistics demonstrated no significant difference for sensitivity (mpMRI: 86%, 95% confidence interval [CI] 81–90; bpMRI: 90%, 95% CI 83–94) or specificity (mpMRI: 73%, 95% CI 64–81; bpMRI: 70%, 95% CI 42–83). The summary receiver operating characteristic curves were comparable for mpMRI (0.87) and bpMRI (0.90).

Conclusions

No significant difference in DTA was found between mpMRI and bpMRI in diagnosing prostate cancer in treatment‐naïve patients. Study heterogeneity warrants cautious interpretation of the results. With replication of our findings in dedicated validation studies, bpMRI may serve as a faster, cheaper, gadolinium‐free alternative to mpMRI.

 

 

 

Video: A transcriptomic signature of tertiary Gleason 5 predicts worse clinicopathological outcome

A transcriptomic signature of tertiary Gleason 5 predicts worse clinicopathological outcome

by Alberto Martini

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; = 0.04) and higher likelihood of falling within the intermediate‐ or high‐risk categories (odds ratio 3.34, 95% CI 1.34–8.35; = 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.

 

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

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

by Riccardo Bertolo (@RicBertolo)

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.

Video: Palliative care use amongst patients with bladder cancer

Palliative care use amongst patients with bladder cancer

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.

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.

Video: The impact on oncological outcomes after RP for PCa of converting soft tissue margins at the apex and bladder neck from tumour‐positive to ‐negative

The impact on oncological outcomes after radical prostatectomy for prostate cancer of converting soft tissue margins at the apex and bladder neck from tumour‐positive to ‐negative

Abstract

Objectives

To assess the impact of conversion from histologically positive to negative soft tissue margins at the apex and bladder neck on biochemical recurrence‐free survival (BCRFS) and distant metastasis‐free survival (DMFS) after radical prostatectomy (RP) for prostate cancer.

Materials and Methods

The records of 2 013 patients who underwent RP and intra‐operative frozen section (IFS) analysis between July 2007 and June 2016 were reviewed. IFS analysis of the urethra and bladder neck was performed, and if malignant or atypical cells remained, further resection with the aim of achieving histological negativity was carried out. Patients were divided into three groups according to the findings: those with a negative surgical margin (NSM), a positive surgical margin converted to negative (NCSM) and a persistent positive surgical margin (PSM).

Results

Among the 2 013 patients, rates of NSMs, NCSMs and PSMs were 75.1%, 4.9%, and 20.0%, respectively. The 5‐year BCRFS rates of patients with NSMs, NCSMs and PSMs were 89.6%, 85.1% and 57.1%, respectively (P < 0.001). In both pathological (p)T2 and pT3 cancers, the 5‐year BCRFS rate for patients with NCSMs was similar to that for patients with NSMs, and higher than for patients with PSMs. The 7‐year DMFS rates of patients with NSMs, NCSMs and PSMs were 97.8%, 99.1% and 89.4%, respectively (P < 0.001). Among patients with pT3 cancers, the 7‐year DMFS rate was significantly higher in the NCSM group than in the PSM group (98.0% vs 86.7%; P = 0.023), but not among those with pT2 cancers (100% vs 96.9%; P = 0.616). The 5‐year BCRFS rate for the NCSM group was not significantly different from that of the NSM group among the patients with low‐ (96.3% vs 95.8%) and intermediate‐risk disease (91.1% vs 82.8%), but was lower than that of the NSM group among patients in the high‐risk group (73.2% vs 54.7%).

Conclusions

Conversion of the soft tissue margin at the prostate apex and bladder neck from histologically positive to negative improved the BCRFS and DMFS after RP for prostate cancer; however, the benefit of conversion was not apparent in patients in the high‐risk group.

 

Video: Vaccines for the prevention of recurrent urinary tract infections: a systematic review

Vaccines for the prevention of recurrent urinary tract infections: a systematic review

Abstract

Objectives

To systematically review the evidence regarding the efficacy of vaccines or immunostimulants in reducing the recurrence rate of urinary tract infections (UTIs).

Materials and Methods

The Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica dataBASE (EMBASE), PubMed, Cochrane Library, World Health Organization (WHO) International Clinical Trials Registry Platform Search Portal, and conference abstracts were searched up to January 2018 for English‐titled citations. Randomised placebo‐controlled trials evaluating UTI recurrence rates in adult patients with recurrent UTIs treated with a vaccine were selected by two independent reviewers according to the Population, Interventions, Comparators, and Outcomes (PICO) criteria. Differences in recurrence rates in study populations for individual trials were calculated and pooled, and risk ratios (RRs) using random effects models were calculated. Risk of bias was assessed using the Cochrane Collaboration’s tool and heterogeneity was assessed using chi‐squared and I2 testing. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to evaluate the quality of evidence (QOE) and summarise findings.

Results

In all, 599 records were identified, of which 10 studies were included. A total of 1537 patients were recruited and analysed, on whom data were presented. Three candidate vaccines were studied: Uro‐Vaxom® (OM Pharma, Myerlin, Switzerland), Urovac® (Solco Basel Ltd, Basel, Switzerland), and ExPEC4V (GlycoVaxyn AG, Schlieren, Switzerland). At trial endpoint, the use of vaccines appeared to reduce UTI recurrence compared to placebo (RR 0.74, 95% confidence interval [CI] 0.67–0.81; low QOE). Uro‐Vaxom showed the greatest reduction in UTI recurrence rate; the maximal effect was seen at 3 months compared with 6 months after initial treatment (RR 0.67, 95% CI 0.57–0.78; and RR 0.78, 95% CI 0.69–0.88, respectively; low QOE). Urovac may also reduce risk of UTI recurrence (RR 0.75, 95% CI 0.63–0.89; low QOE). ExPEC4V does not appear to reduce UTI recurrence compared to placebo at study endpoint (RR 0.82, 95% CI 0.62–1.10; low QOE). Substantial heterogeneity was observed across the included studies (chi‐squared = 54.58; P < 0.001, I2 = 84%).

Conclusions

While there is evidence for the efficacy of vaccines in patients with recurrent UTIs, significant heterogeneity amongst these studies renders interpretation and recommendation for routine clinical use difficult at present. Further randomised trials using consistent definitions and endpoints are needed to study the long‐term efficacy and safety of vaccines for infection prevention in patients with recurrent UTIs.

Video: Evaluation of axitinib to downstage cT2a renal tumours and allow partial nephrectomy: a phase II study

Evaluation of axitinib to downstage cT2a renal tumours and allow partial nephrectomy: a phase II study

Abstract

Objective

To evaluate the ability of neoadjuvant axitinib to reduce the size of T2 renal cell carcinoma (RCC) for shifting from a radical nephrectomy (RN) to a partial nephrectomy (PN) indication, offering preservation of renal function.

Patients and Methods

Patients with cT2aN0NxM0 clear‐cell RCC, considered not suitable for PN, were enrolled in a prospective, multicentre, phase II trial (AXIPAN). Axitinib 5 mg, and up to 7–10 mg, was administered twice daily, for 2–6 months before surgery, depending on the radiological response. The primary outcome was the number of patients receiving PN for a tumour <7 cm in size after neoadjuvant axitinib.

Results

Eighteen patients were enrolled. The median (range) tumour size and RENAL nephrometry score were 76.5  (70–98) mm and 11 (7–11), respectively. After axitinib neoadjuvant treatment, 16 tumours decreased in diameter, with a median size reduction of 17% (64.0 vs 76.5 mm; P < 0.001). The primary outcome was considered achieved in 12 patients who underwent PN for tumours <7 cm. Sixteen patients underwent PN. Axitinib was tolerated in the present study, as has been previously shown in the metastatic setting. Five patients had grade 3 adverse events. Five patients experienced Clavien III–V post‐surgery complications. At 2‐year follow‐up, six patients had metastatic progression, and two had a recurrence.

Conclusion

Neoadjuvant axitinib in cT2 ccRCC is feasible and, even with a modest decrease in size, allowed a tumour shrinkage <7 cm in 12 cases; however, PN procedures remained complex, requiring surgical expertise with possible morbidity.

Video: Prostatic capsular incision during RP has important oncological implications. A systematic review and meta‐analysis

Prostatic capsular incision during radical prostatectomy has important oncological implications. A systematic review and meta‐analysis

Abstract

Introduction

Capsular Incision (CapI) is an iatrogenic breach of the prostatic capsule during radical prostatectomy that can cause positive surgical margins (PSM) in organ‐confined (pT2) prostate cancer (PCa), or the retention of benign prostatic tissue. We systematically interrogated the literature in order to clarify the definition of CapI, and the implications of this event for rates of PSM and biochemical recurrence (BCR).

Methods

A literature search was conducted according to PRISMA criteria using the search terms ‘CapI’ AND ‘prostatectomy’ and variations of each. 18 studies were eligible for inclusion.

Results

A total of 51,057 radical prostatectomy specimens were included. The incidence of CapI ranged from 1.3‐54.3%. CapI definitions varied, and included a breach of the prostatic capsule “exposing both benign or malignant PCa cells”, “malignant tissue only”, or “benign tissue only”. The incidence of PSM due to CapI ranged from 2.8 – 71.7%. Our meta‐analysis results found that when CapI was defined as “exposing malignant tissue only in organ‐confined prostate cancer” there was an increased risk of BCR compared to patients with pT2 disease and no CapI (RR 3.53, 95%CI 2.82‐4.41; p < 0.00001).

Conclusions

The absolute impact of CapI on oncological outcomes is currently unclear due to inconsistent definitions. However, the data implies an association between CapI and PSM and BCR. Reporting of possible areas of CapI on the operation note, or marking areas of concern on the specimen, are critical to assist CapI recognition by the pathologist.

 

Video: The relationship between oxidative stress and lower urinary tract symptoms: Results from the community health survey in Japan

The relationship between oxidative stress and lower urinary tract symptoms: Results from the community health survey in Japan

 

Abstract

Objective

To investigate the relationship between oxidative stress and lower urinary tract symptoms (LUTS) in a community‐dwelling population.

Materials and Methods

The cross‐sectional study included 1 113 people who participated in the Iwaki Health Promotion Project of 2015 in Hirosaki, Japan. LUTS were assessed using structured questionnaires, including the International Prostate Symptom Score (IPSS) and the Overactive Bladder Symptom Score (OABSS). IPSS > 7, OABSS > 5, nocturia score > 1, or urge incontinence score > 1 were defined as moderate to severe symptoms. 8‐Hydroxy‐2′‐deoxyguanosine (8‐OHdG) and advanced glycation end products (AGEs) were measured by urine analysis and skin autofluorescence, respectively. The relationship between oxidative stress and LUTS was investigated using logistic regression analyses.

Results

This study included 431 men and 682 women. AGEs and 8‐OHdG levels were significantly higher in severe forms of LUTS. Multivariate logistic regression analyses showed that AGE levels were significantly associated with a higher frequency of nocturia but were not associated with IPSS, OABSS or urge incontinence. No significant association was observed between LUTS and 8‐OHdG levels.

Conclusions

We observed a significant association between AGE levels and nocturia score > 1. Further research is necessary to clarify a possible causal relationship between oxidative stress and nocturia.

Video: Cognitive training for technical and non‐technical skills in robotic surgery

Cognitive training for technical and non‐technical skills in robotic surgery: a randomised controlled trial

Abstract

Objective

To investigate the effectiveness of motor imagery (MI) for technical skill and non‐technical skill (NTS) training in minimally invasive surgery (MIS).

Subjects and Methods

A single‐blind, parallel‐group randomised controlled trial was conducted at the Vattikuti Institute of Robotic Surgery, King’s College London. Novice surgeons were recruited by open invitation in 2015. After basic robotic skills training, participants underwent simple randomisation to either MI training or standard training. All participants completed a robotic urethrovesical anastomosis task within a simulated operating room. In addition to the technical task, participants were required to manage three scripted NTS scenarios. Assessment was performed by five blinded expert surgeons and a NTS expert using validated tools for evaluating technical skills [Global Evaluative Assessment of Robotic Skills (GEARS)] and NTS [Non‐Technical Skills for Surgeons (NOTSS)]. Quality of MI was assessed using a revised Movement Imagery Questionnaire (MIQ).

Results

In all, 33 participants underwent MI training and 29 underwent standard training. Interrater reliability was high, Krippendorff’s α = 0.85. After MI training, the mean (sd) GEARS score was significantly higher than after standard training, at 13.1 (3.25) vs 11.4 (2.97) (P = 0.03). There was no difference in mean NOTSS scores, at 25.8 vs 26.4 (P = 0.77). MI training was successful with significantly higher imagery scores than standard training (mean MIQ score 5.1 vs 4.5, P = 0.04).

Conclusions

Motor imagery is an effective training tool for improving technical skill in MIS even in novice participants. No beneficial effect for NTS was found.

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