Strategies to maximise patient comfort during extracorporeal shockwave lithotripsy - A randomised controlled trial.

BACKGROUND/PURPOSE OF STUDY: We aim to assess if distraction techniques improve patient comfort tolerability of SWL. METHODS: We carried out a prospective randomised controlled trial of SWL-naïve patients attending for treatment. Patients were randomised into three groups and offered oral analgesia as standard of care. Group 1 (n = 19) received stress balls to squeeze during treatment. Group 2 (n = 19) listened to music during treatment. Group 3 (n = 17) received standard of care only. All patients completed a validated health anxiety inventory score prior to treatment. All patients completed a validated pain questionnaire and visual analogue scale (VAS) after treatment. Primary outcomes were completion of SWL treatment and pain score results. RESULTS: 55 patients attending for SWL were randomised. There was no difference in stone size or position, presence of a stent, height or weight between the groups. VAS scores were lower in controls compared to Group 1 (1.93 vs 3.69, p = 0.08). On subgroup analysis of non-anxious patients, pain questionnaire scores were lower in controls compared to Group 1 (2.58 vs 4.77, p = 0.06). VAS scores were lower in patients who received optional analgesia alone than in patients who received stress balls alone (1.92 vs 4.07, p = 0.05). Across all subgroups, pain scores were lower in the control group compared to the distraction groups, but did not achieve significance. CONCLUSIONS: In conclusion, distraction techniques should not replace standard of care for analgesia during SWL. This study was registered with clinicaltrials.gov (identifier NCT03379922).

A risk calculator to inform the need for a prostate biopsy: a rapid access clinic cohort.

BACKGROUND: Prostate cancer (PCa) represents a significant healthcare problem. The critical clinical question is the need for a biopsy. Accurate risk stratification of patients before a biopsy can allow for individualised risk stratification thus improving clinical decision making. This study aims to build a risk calculator to inform the need for a prostate biopsy. METHODS: Using the clinical information of 4801 patients an Irish Prostate Cancer Risk Calculator (IPRC) for diagnosis of PCa and high grade (Gleason ≥7) was created using a binary regression model including age, digital rectal examination, family history of PCa, negative prior biopsy and Prostate-specific antigen (PSA) level as risk factors. The discrimination ability of the risk calculator is internally validated using cross validation to reduce overfitting, and its performance compared with PSA and the American risk calculator (PCPT), Prostate Biopsy Collaborative Group (PBCG) and European risk calculator (ERSPC) using various performance outcome summaries. In a subgroup of 2970 patients, prostate volume was included. Separate risk calculators including the prostate volume (IPRCv) for the diagnosis of PCa (and high-grade PCa) was created. RESULTS: IPRC area under the curve (AUC) for the prediction of PCa and high-grade PCa was 0.6741 (95% CI, 0.6591 to 0.6890) and 0.7214 (95% CI, 0.7018 to 0.7409) respectively. This significantly outperforms the predictive ability of cancer detection for PSA (0.5948), PCPT (0.6304), PBCG (0.6528) and ERSPC (0.6502) risk calculators; and also, for detecting high-grade cancer for PSA (0.6623) and PCPT (0.6804) but there was no significant improvement for PBCG (0.7185) and ERSPC (0.7140). The inclusion of prostate volume into the risk calculator significantly improved the AUC for cancer detection (AUC = 0.7298; 95% CI, 0.7119 to 0.7478), but not for high-grade cancer (AUC = 0.7256; 95% CI, 0.7017 to 0.7495). The risk calculator also demonstrated an increased net benefit on decision curve analysis. CONCLUSION: The risk calculator developed has advantages over prior risk stratification of prostate cancer patients before the biopsy. It will reduce the number of men requiring a biopsy and their exposure to its side effects. The interactive tools developed are beneficial to translate the risk calculator into practice and allows for clarity in the clinical recommendations.

European Randomised Study of Screening for Prostate Cancer (ERSPC) risk calculators significantly outperform the Prostate Cancer Prevention Trial (PCPT) 2.0 in the prediction of prostate cancer: a multi-institutional study.

OBJECTIVE: To analyse the performance of the Prostate Cancer Prevention Trial Risk Calculator (PCPT-RC) and two iterations of the European Randomised Study of Screening for Prostate Cancer (ERSPC) Risk Calculator, one of which incorporates prostate volume (ERSPC-RC) and the other of which incorporates prostate volume and the prostate health index (PHI) in a referral population (ERSPC-PHI). PATIENTS AND METHODS: The risk of prostate cancer (PCa) and significant PCa (Gleason score ≥7) in 2001 patients from six tertiary referral centres was calculated according to the PCPT-RC and ERSPC-RC formulae. The calculators' predictions were analysed using the area under the receiver-operating characteristic curve (AUC), calibration plots, Hosmer-Lemeshow test for goodness of fit and decision-curve analysis. In a subset of 222 patients for whom the PHI score was available, each patient's risk was calculated as per the ERSPC-RC and ERSPC-PHI risk calculators. RESULTS: The ERSPC-RC outperformed the PCPT-RC in the prediction of PCa, with an AUC of 0.71 compared with 0.64, and also outperformed the PCPT-RC in the prediction of significant PCa (P<0.001), with an AUC of 0.74 compared with 0.69. The ERSPC-RC was found to have improved calibration in this cohort and was associated with a greater net benefit on decision-curve analysis for both PCa and significant PCa. The performance of the ERSPC-RC was further improved through the addition of the PHI score in a subset of 222 patients. The AUCs of the ERSPC-PHI were 0.76 and 0.78 for PCa and significant PCa prediction, respectively, in comparison with AUC values of 0.72 in the prediction of both PCa and significant PCa for the ERSPC-RC (P = 0.12 and P = 0.04, respectively). The ERSPC-PHI risk calculator was well calibrated in this cohort and had an increase in net benefit over that of the ERSPC-RC. CONCLUSIONS: The performance of the risk calculators in the present cohort shows that the ERSPC-RC is a superior tool in the prediction of PCa; however the performance of the ERSPC-RC in this population does not yet warrant its use in clinical practice. The incorporation of the PHI score into the ERSPC-PHI risk calculator allowed each patient's risk to be more accurately quantified. Individual patient risk calculation using the ERSPC-PHI risk calculator can be undertaken in order to allow a systematic approach to patient risk stratification and to aid in the diagnosis of PCa.

A critical analysis of deficiencies in the quality of information contained in prostate multiparametric MRI requests and reports.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) has been increasingly recognised as an important tool in the diagnosis of prostate cancer. PI-RADSv2 guidelines recommend that important clinical information including prostate-specific antigen (PSA) levels, examination findings, and biopsy information should be included in mpMRI requests. PIRADS score and PSA density (PSAD) are both independent predictors for the presence of a clinically significant prostate cancer. AIMS: This study aims to evaluate the quality of mpMRI requests and reports at our institution in accordance with these parameters. METHODS: All prostate mpMRIs performed by radiology services in Galway University Hospital between 1st September 2019 and 1st March 2020 were reviewed. Exclusion criteria were applied. Requests and reports were analysed for the presence of the following parameters: PSA-results, examination findings, biopsy information, PI-RADS score, prostate volume, and PSAD. RESULTS: A total of 586 mpMRIs were performed, and of these, 546 were included. PSA value was provided in 497 (91%) of requests, exam findings in 355 (65%), and biopsy information in 452 (82%). PIRADS score was included in 224 (41%) of reports, prostate volume in 178 (32.6%), and PSAD in 106 (19%). CONCLUSIONS: Great variation in the quality of information contained in both requests and reports for prostate mpMRIs exists within our service. We aim to improve this by collaborating with our radiology colleagues to develop a proforma for requesting and reporting of mpMRIs for our radiology systems to ensure important clinical and radiological information is provided in future.

A case report of mucinous tubular and spindle cell carcinoma of the kidney.

Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare type of kidney tumor that has only recently been described, with less than eighty cases in the literature. This was only recognized as a specific entity in the World Health Organization 2004 classification of Renal Cell Carcinoma (RCC). MTSCCs are polymorphic renal neoplasms characterized by small, elongated tubules lined by cuboidal cells with cords of spindled cells separated by pale mucinous stroma. We report the case of a 57 year old lady who had an incidental finding of a mass in her right kidney. The radiological features were consistent with a RCC and following a multidisciplinary team discussion she underwent a laparoscopic radical nephrectomy. Macroscopic examination revealed a well circumscribed 6.5 × 6 × 6.5 cm right lower pole mass. Histologically it was composed of elongated tubules, small tubules and papillary structures with a necrotic centre. The cells demonstrated cuboidal and spindle cell morphology. Histological grade was Fuhrman grade 2. The majority of MTSCCs are indolent, and there are only two reports of distant metastases which responded favorably to adjuvant sunitinib. To date there is no international consensus on long term surveillance of these patients. Due of the favorable prognosis with this type of tumor, MTSCC must be differentiated from papillary renal cell carcinoma to avoid administration of excessive adjuvant treatment to patients.

A double-blind randomized controlled clinical trial to assess the effect of Doppler optimized intraoperative fluid management on outcome following radical cystectomy.

PURPOSE: Cardiovascular optimization via esophageal Doppler can minimize gastrointestinal hypoperfusion, reducing the risk of multiple organ dysfunction and postoperative complications during major surgery. We assessed the effect of esophageal Doppler guided cardiovascular optimization in patients undergoing radical cystectomy. MATERIALS AND METHODS: We conducted a prospective, randomized, double-blind controlled trial at a United Kingdom teaching hospital between 2006 and 2009. A total of 66 patients were randomized to a control arm (34) and an intervention arm (32). The control group received standard intraoperative fluids. The intervention group received (additional) Doppler guided fluid. Primary outcomes were markers of gastrointestinal morbidity such as ileus, flatus and bowel opening. Secondary outcomes were postoperative nausea and vomiting, wound infection and operative intravenous fluid volumes (total and hourly). RESULTS: There were significant reductions in the control and intervention arms in the incidence of ileus (18 vs 7, p <0.001), flatus (5.36 vs 3.55 days, p <0.01) and bowel opening (9.79 vs 6.53 days, p = 0.02), respectively. Nausea and vomiting were significantly reduced in the study group at 24 and 48 hours postoperatively (11 vs 3, p <0.01 and 13 vs 1, p <0.0001). Wound infection rates were significantly reduced (8 vs 1 superficial, p <0.01 and 10 vs 2 combined, p <0.01). Study patients received significantly higher volumes (ml/kg per minute) of intravenous fluid (0.19 vs 0.23, p <0.01) related to a significantly higher volume (ml/kg) in the first hour of surgery (14.1 vs 21.0, p = 0.0001). CONCLUSIONS: Cardiovascular optimization using esophageal Doppler significantly improved postoperative markers of gastrointestinal function.

Measuring a new facet of post traumatic growth: Development of a scale of physical post traumatic growth in men with prostate cancer.

PURPOSE: This study developed a measure of physical post traumatic growth (physical post traumatic growth inventory; P-PTGI) in men with prostate cancer. METHODS: A pool of items was created from themes identified in a qualitative study. A quantitative study was then conducted to assess the psychometric properties of the P-PTGI in a sample of 693 prostate cancer survivors. RESULTS: Tests of dimensionality revealed that the 20-item P-PTGI contained two factors: Health Autonomy and Health Awareness. Results demonstrated that scale score reliability for the P-PTGI and its subscales was excellent. In support of the scale's convergent validity, scores on the P-PTGI correlated positively with mindfulness and quality of life, and correlated negatively with depression and anxiety. A statistically significant correlation between the P-PTGI and another robust indicator of post traumatic growth attests to its concurrent validity. CONCLUSIONS: While further investigation of the P-PTGI's psychometric properties is required, preliminary findings are promising.

Outcomes from the Introduction of a Combined Urology Outpatient Clinic.

BACKGROUND: A combined urology clinic staffed by four consultants and four non-consultant hospital doctors (NCHDs) was introduced in our institution in October 2015. This clinic is supported by a pre-clinic radiology meeting and a synchronous urology clinical nurse specialist (CNS) clinic with protected uroflow/trial of void slots. Herein, we report on the outcomes of this clinic in comparison with the standard format of urology outpatient review. METHODS: We carried out a retrospective review of clinic attendances from May to July 2016. We recorded the number of new and return attendances, which team members had reviewed the patient and patient outcomes. We also calculated the waiting times for new patients to be reviewed in the outpatient clinic. RESULTS: The combined urology clinic reviewed an average of 12 new and 46 return patients per clinic. The standard urology clinic reviewed an average of 8 new and 23 return patients per clinic. 54% of patients were seen by a consultant in the combined urology clinic, and 20% of patients were seen by a consultant in the standard urology clinic. The rate of patient discharge for new patients was 14.8% in the combined clinic compared to 5.9% in the standard clinic. Overall patient outcomes are outlined in the table. The waiting time for review of new patients in the combined clinic was reduced by 39% from 144 days to 89 days over a one-year period. CONCLUSIONS: The introduction of a combined urology outpatient clinic with the support of pre-clinic radiology meeting and synchronous urology CNS clinic facilitates patient discharge.

Increasing detection of significant prostate cancer in younger men - ten year trends in prostate cancer risk profile in the Mid-West of Ireland.

INTRODUCTION: Although PSA (prostate specific antigen) based screening for prostate cancer (PCa) is controversial, an increasing number of men are undergoing Transrectal Ultrasound Guided prostate biopsy (TRUSPB) through primary care-based PSA testing and referral to hospitals. The aim of our study was to investigate presenting risk profiles of PCa over the last decade in a cohort of men in Ireland and to examine any change in the same over this time period. MATERIAL AND METHODS: The hospital patient administration system was analysed for patients who underwent TRUSPB from January 2005 to December 2015. Clinically significant PCa was defined as Gleason score of 7 or above. RESULTS: Complete data was available on 2391 TRUSPB patients: number of biopsies increased by 53%, median age decreased by 0.9%, median PSA decreased by 6% (p = 0.001, ANOVA) and abnormal DRE increased by 9% (p = 0.001, chi square). Overall positive biopsy was 44% and significant cancer rate was 21%. There was a significant change in trend of detection (p = 0.02) with average annual increase in significant cancer of 3%. The median age of the significant cancer cohort reduced by 1% and the PSA at diagnosis reduced by 9%. In younger men (<50 years), the rate of significant cancer detection increased by 18%. CONCLUSIONS: Significant PCa detection increased across all age groups but recently, a younger patient profile was diagnosed with high-grade disease. This paves the way for future research on early-onset PCa. Younger patients with significant disease would result in increasing number of patients being eligible for radical treatment with implications on health resource planning and provision.

Alteration in urinary matrix metalloproteinase-9 to tissue inhibitor of metalloproteinase-1 ratio predicts recurrence in nonmuscle-invasive bladder cancer.

PURPOSE: The purpose is to assess the prognostic significance of matrix metalloproteinase (MMP)-9 in patients with bladder cancer using a combination of ELISA (to measure MMP-9 in voided urine) and immunohistochemistry (to study MMP-9 in bladder tumors). The relationship between MMP-9 and its principal inhibitor, tissue inhibitor of metalloproteinase (TIMP)-1 (in voided urine samples) was also studied. EXPERIMENTAL DESIGN: A total of 134 patients with bladder tumors (7 cis, 76 T(a), 27 T(1), 24 T(2)-T(4); 40 G1, 43 G2, and 44 G3), 33 patients with benign urological conditions, and 36 healthy volunteers was studied. Samples from 106 patients with bladder cancer and 12 controls were stained for MMP-9. Clinical follow-up data were available on 116 patients (median: 25 months; range: 4-36 months). RESULTS: MMP-9 was present in all urine samples analyzed. There were no differences between patients with cancer and patients with benign disorders. However, patients had significantly higher urinary MMP-9 than normal volunteers (P = 0.0167). Urinary MMP-9 was associated with bladder tumors of advanced stage (P = 0.0065) and large size (P < 0.0001) but not with grade (P = 0.14), multiplicity (P = 0.31), recurrence (P = 0.55), progression (P = 0.83), or survival (P = 0.55). Low MMP-9:TIMP-1 ratios in patients with nonmuscle-invasive tumors were associated with higher recurrence rates (P = 0.0035). Sixty percent (64 of 106) of bladder tumor specimens expressed MMP-9 compared with none of 12 normal urothelial biopsies (P < 0.0001). MMP-9 staining was associated with tumor size (P = 0.014), disease progression (P = 0.005), and poor disease-specific survival (P = 0.022) but was unrelated to tumor stage (P = 0.46), grade (P = 0.26), multiplicity (P = 0.85), or recurrence rate (P = 0.62). CONCLUSIONS: High urinary MMP-9 levels are associated with large bladder tumors. A low urinary MMP-9:TIMP-1 ratio may indicate a higher risk of intraluminal nonmuscle-invasive tumor recurrence and may assist in planning follow-up surveillance protocols.

A Circulating MicroRNA Signature as a Biomarker for Prostate Cancer in a High Risk Group.

INTRODUCTION: Mi(cro)RNAs are small non-coding RNAs whose differential expression in tissue has been implicated in the development and progression of many malignancies, including prostate cancer. The discovery of miRNAs in the blood of patients with a variety of malignancies makes them an ideal, novel biomarker for prostate cancer diagnosis. The aim of this study was to identify a unique expression profile of circulating miRNAs in patients with prostate cancer attending a rapid access prostate assessment clinic. METHODS: To conduct this study blood and tissue samples were collected from 102 patients (75 with biopsy confirmed cancer and 27 benign samples) following ethical approval and informed consent. These patients were attending a prostate assessment clinic. Samples were reverse-transcribed using stem-loop primers and expression levels of each of 12 candidate miRNAs were determined using real-time quantitative polymerase chain reaction. miRNA expression levels were then correlated with clinicopathological data and subsequently analysed using qBasePlus software and Minitab. RESULTS: Circulating miRNAs were detected and quantified in all subjects. The analysis of miRNA mean expression levels revealed that four miRNAs were significantly dysregulated, including let-7a (p = 0.005) which has known tumour suppressor characteristics, along with miR-141 (p = 0.01) which has oncogenic characteristics. In 20 patients undergoing a radical retropubic-prostatectomy, the expression levels of miR-141 returned to normal at day 10 post-operatively. A panel of four miRNAs could be used in combination to detect prostate cancer with an area under the curve (AUC) of 0.783 and a PPV of 80%. CONCLUSION: These findings identify a unique expression profile of miRNA detectable in the blood of prostate cancer patients. This confirms their use as a novel, diagnostic biomarker for prostate cancer.

Feasibility study of a randomized controlled trial comparing docetaxel chemotherapy and androgen deprivation therapy with sequential prostatic biopsies from patients with advanced non-castration-resistant prostate cancer.

BACKGROUND AND OBJECTIVE: Sequential tissue biopsies taken during clinical trials of novel systemic anticancer therapies for advanced prostate cancer (PCa) may aid pharmacodynamic evaluation and biomarker discovery. We conducted a single institution phase-II open-labeled randomized study to assess the safety, tolerability, and early efficacy of docetaxel chemotherapy plus androgen deprivation therapy (ADT) vs. ADT alone for patients with advanced non-castration-resistant PCa with sequential prostatic biopsies. PATIENTS AND METHODS: We randomized 30 patients with newly diagnosed high-grade locally advanced or metastatic (cT3-4/N0-1/M0-1) PCa to receive ADT with (n = 15) or without (n = 15) docetaxel. Transrectal ultrasound-guided prostatic biopsies were taken at randomization and ~22 weeks after treatment initiation. Primary end point: biochemical response rate. Secondary end points: time to progression and tumor profiling. RESULTS: Both treatments appear to be well tolerated, and there was no difference in mean nadir prostate-specific antigen and time to prostate-specific antigen relapse between treatment arms (P>0.05). No adverse effects of pre- and post-treatment prostatic biopsies were observed. The study was neither designed nor sufficiently powered to demonstrate statistically significant differences in oncological outcomes or safety profiles between the 2 treatment arms. CONCLUSIONS: Despite the lack of statistical power, our study suggests that docetaxel and ADT in combination may be well tolerated with apparently similar short-term efficacy compared with ADT alone for high-grade locally advanced or metastatic non-castration-resistant PCa, Sequential prostatic biopsies may provide tissue for tumor profiling to yield mechanistic or prognostic insights relating to novel systemic anticancer therapies.

Developing a laparoscopic radical prostatectomy service: defining the learning curve.

BACKGROUND AND PURPOSE: Laparoscopic radical prostatectomy (LRP) is an established treatment for patients with prostate cancer in selected centers with appropriate expertise. We studied our single-center experience of developing a LRP service and subsequent training of two additional surgeons by the initial surgeon. We assessed the learning curve of the three surgeons with regard to perioperative outcomes and oncologic results. PATIENTS AND METHODS: Three hundred consecutive patients underwent a LRP between January 2005 and April 2011. Patients were divided into three equal groups (1-100 group 1], 101-200 [group 2], and 201-300 [group 3]). Age, American Society of Anesthesiologists score, preoperative comorbidities, and indications for LRP were comparable for all three patient groups. Perioperative and oncologic outcomes were compared across all three groups to assess the impact of the learning curve for LRP. All surgical complications were classified using the Clavien-Dindo system (CDS). RESULTS: The mean age was 61.9 years (range 46-74 y). There was a significant reduction in the mean operative time (P<0.05), mean blood loss (P<0.05), mean duration of hospital stay (P<0.05), and duration of catherization (P<0.05) between the three groups as the series progressed. The two most important factors predictive of positive surgical margins at LRP were the initial prostate-specific antigen level and tumor stage at diagnosis. The overall positive margin rate was 27.7%. For pT(2) tumors, the positive margin rate was 21%, while patients with pT(3) tumors had a positive margin of 44%. For pT(2) tumors, positive margin rates decreased with increasing experience (group 1, 27% vs group 2, 17% vs group 3, 19%). The incidence of major complications--ie, grade CDS score ≤ III--was 4.6% (14/300). CONCLUSION: LRP is a safe procedure with low morbidity. As surgeons progress through the learning curve, perioperative parameters and oncologic outcomes improve. Using a carefully mentored approach, LRP can be safely introduced as a new procedure without compromising patient outcomes.

The impact of early re-resection in patients with pT1 high-grade non-muscle invasive bladder cancer.

AIM: To evaluate the impact of early re-resection on the incidence of tumour recurrence and progression in patients with pT1 high-grade non-muscle invasive bladder cancer (HG-NMIBC). PATIENTS AND METHODS: From 2001 to 2008, 486 consecutive patients were diagnosed with pT1 HG-NMIBC. Data were collected retrospectively which included patient demographics, histological parameters including the presence of detrusor muscle at initial TUR and at re-resection, adjuvant intravesical therapy, and recurrence and progression rates. Early re-resection was performed within six weeks of initial TUR. Patients comprised those who underwent an early re-resection (Group A, n = 172) and those who did not (Group B, n = 314). RESULTS: At initial TUR, detrusor muscle was present in 61% (n = 105) of patients in Group A and 76% (n = 240) of patients in Group B. At early re-resection, detrusor muscle was present in 77.9% of cases. A residual tumour was present in 54.6% of re-resected cases. The overall incidence of tumour recurrence was 35% and 42% in Groups A and B, respectively. During follow-up, there was a significantly higher rate of tumour stage progression in patients who did not undergo early re-resection (Group B 14.4% vs. Group A 3.3%, P < 0.05). CONCLUSIONS: Early re-resection facilitates accurate staging and clearance of residual disease. Subsequent rates of tumour stage progression are significantly improved. We advocate early re-resection for all patients with HG-NMIBC.

Expression of S100A4 protein is associated with metastasis and reduced survival in human bladder cancer.

The calcium-binding protein S100A4 induces the metastatic phenotype in rodent models of breast cancer and its expression correlates strongly with reduced survival in human breast cancer. The expression of S100A4 in normal bladders and 101 bladder tumours has been studied using immunocytochemistry. Moderate or strong expression of S100A4 was found in 28% of the tumours, whilst the remaining tumours and normal urothelium either failed to stain or showed weak staining. S100A4 staining was more frequently observed in invasive bladder tumours than in non-invasive tumours (p<0.05). In invasive tumours, S100A4 staining was usually strongest in invasive regions and single infiltrating cells. Statistically significant associations were found between S100A4 expression and metastasis (p=0.0003) and reduced survival (p<0.0001). It is concluded that S100A4 expression may play an important role in bladder cancer and may identify a subgroup of patients at increased risk of metastasis who should be considered for adjuvant systemic therapy.