Diagnostic evaluation of upper tract urothelial carcinoma: can we safely omit diagnostic ureteroscopy?

OBJECTIVE: To identify clinicopathological or radiological factors that may predict a diagnosis of upper urinary tract urothelial cell carcinoma (UTUC) to inform which patients can proceed directly to radical nephroureterectomy (RNU) without the delay for diagnostic ureteroscopy (URS). PATIENTS AND METHODS: All consecutive patients investigated for suspected UTUC in a high-volume UK centre between 2011 and 2017 were identified through retrospective analysis of surgical logbooks and a prospectively maintained pathology database. Details on clinical presentation, radiological findings, and URS/RNU histopathology results were evaluated. Multivariate regression analysis was performed to evaluate predictors of a final diagnosis of UTUC. RESULTS: In all, 260 patients were investigated, of whom 230 (89.2%) underwent URS. RNU was performed in 131 patients (50.4%), of whom 25 (9.6%) proceeded directly without URS - all of whom had a final histopathological diagnosis of UTUC - and 15 (11.5%) underwent RNU after URS despite no conclusive histopathological confirmation of UTUC. Major surgery was avoided in 77 patients (33.5%) where a benign or alternative diagnosis was made on URS, and 14 patients (6.1%) underwent nephron-sparing surgery. Overall, 178 patients (68.5%) had a final diagnosis of UTUC confirmed on URS/RNU histopathology. On multivariate logistic regression analysis, a presenting complaint of visible haematuria (hazard ratio [HR] 5.17, confidence interval [CI] 1.91-14.0; P = 0.001), a solid lesion reported on imaging (HR 37.8, CI = 11.7-122.1; P < 0.001) and a history of smoking (HR 3.07, CI 1.35-6.97; P = 0.007), were predictive of a final diagnosis of UTUC. From this cohort, 51 (96.2%) of 53 smokers who presented with visible haematuria and who had a solid lesion on computed tomography urogram had UTUC on final histopathology. CONCLUSION: We identified specific factors which may assist clinicians in selecting which patients may reliably proceed to RNU without the delay of diagnostic URS. These findings may inform a prospective multicentre analysis including additional variables such as urinary cytology.

Assessment of association between lower ureteric excision technique and oncological outcomes for upper urinary tract urothelial carcinoma: retrospective analysis from the Scottish Renal Cancer Consortium.

PURPOSE: Nephroureterectomy(NU) remains the gold-standard surgical option for the management of upper urinary tract urothelial carcinoma(UTUC). Controversy exists regarding the optimal excision technique of the lower ureter. We sought to compare post-UTUC bladder tumour recurrence across the Scottish Renal Cancer Consortium(SRCC). METHODS: Patients who underwent NU for UTUC across the SRCC 2012-2019 were identified. The impact of lower-end surgical technique along with T-stage, N-stage, tumour location and focality, positive surgical margin, pre-NU ureteroscopy, upper-end technique and adjuvant mitomycin C administration were assessed by Kaplan-Meier and Cox-regression. The primary outcome was intra-vesical recurrence-free survival (B-RFS). RESULTS: In 402 patients, the median follow-up was 29 months. The lower ureter was managed by open transvesical excision in 90 individuals, transurethral and laparoscopic dissection in 76, laparoscopic or open extra-vesical excision in 31 and 42 respectively, and transurethral dissection and pluck in 163. 114(28.4%) patients had a bladder recurrence during follow-up. There was no difference in B-RFS between lower-end techniques by Kaplan-Meier (p = 0.94). When all factors were taken into account by adjusted Cox-regression, preceding ureteroscopy (HR 2.65, p = 0.001), lower ureteric tumour location (HR 2.16, p = 0.02), previous bladder cancer (HR 1.75, p = 0.01) and male gender (HR 1.61, p = 0.03) were associated with B-RFS. CONCLUSION: These data suggest in appropriately selected patients, lower ureteric management technique does not affect B-RFS. Along with lower ureteric tumour location, male gender and previous bladder cancer, preceding ureteroscopy was associated with a higher recurrence rate following NU, and the indication for this should be carefully considered.

Striated Muscle in Radical Prostatectomy Specimens: A Marker of Apical Dissection Quality and an Independent Predictor of Urinary Continence after Endoscopic Extraperitoneal Radical Prostatectomy.

INTRODUCTION: The study aimed to determine if the presence and amount of striated muscle on the apical sections of the cruciate sections of laparoscopic radical prostatectomy (LRP) specimens predict early and long-term urinary continence outcomes. PATIENTS AND METHODS: We conducted a retrospective review of our prospectively collected single surgeon LRP database. We identified patients based on their continence outcomes (continent (0 pads) or incontinent at 12 months), with an approximate even spread early continent and incontinent patients). An uropathologist separate from the urology team was blinded to outcome and assessed each patients' apical cruciate sections (H&E stained) for the presence, percentage and maximal diameter of muscle and extraprostatic tissue on these sections. Specifically 2 scoring systems were used: (1) semi-quantitative estimation of percentage of muscle on the apical cruciate sections (low <5% and high >5%) and (2) percentage of total extraprostatic tissue on cruciate section (low <10% and high >10%). Logistic regression and classification and regression tree analyses were performed to identify the predictors of urinary incontinence (UI). RESULTS: In total 80 patients were analyzed, 38 were continent and 42 were incontinent at 12 months follow-up. The percentage of extraprostatic tissue/muscle being an independent predictor of being wet at 12 months (p = 0.002) on multivariate regression along with age (p = 0.04). Using percentage of extraprostatic tissue in cruciate section (high >10%) to predict UI at 12 months, it yielded 71% sensitivity, 82% specificity, 81% PPV, 72% NPV and 76% accuracy. CONCLUSION: The use of simple additional reporting of muscle and extraprostatic tissue on the apical sections of RP specimens can help to better predict the likelihood of continence return.

Consultation audio-recording reduces long-term decision regret after prostate cancer treatment: A non-randomised comparative cohort study.

INTRODUCTION: The life expectancy of prostate patients is long and patients will spend many years carrying the burdens & benefits of the treatment decisions they have made, therefore, it is vital that decisions on treatments are shared between patient and physician. The objective was to determine if consultation audio-recording improves quality of life, reduces regret or improves patient satisfaction in comparison to standard counselling. PATIENTS AND METHODS: In 2012 we initiated consultation audio-recordings, where patients are given a CD of their consultation to keep and replay at home. We conducted a prospective non-randomised study of patient satisfaction, quality of life (QOL) and decision regret at 12 months follow-up using posted validated questionnaires for the audio-recording (AR) patients and a control cohort. Qualitative and thematic analyses were used. RESULTS: Forty of 59 patients in the AR group, and 27 of 45 patients in the control group returned the questionnaires. Patient demographics were similar in both groups with no statistically significant differences between the two groups. Decision regret was lower in the audio-recording group (11/100) vs control group (19/100) (p = 0.04). The risk ratio for not having any long-term decision regret was 5.539 (CI 1.643-18.674), with NNT to prevent regret being 4. Regression analysis showed that receiving audio-recording was strongest predictor for absence of regret even greater than potency and incontinence. CONCLUSION: The study has shown that audio-recording clinic consultation reduces long-term decision regret, increases patient information recall, understanding and confidence in their decision. There is great potential for further expansion of this low-cost intervention.

Contemporary practice and technique-related outcomes for radical prostatectomy in the UK: a report of national outcomes.

OBJECTIVE: To determine current radical prostatectomy (RP) practice in the UK and compare surgical outcomes between techniques. PATIENTS AND METHODS: All RPs performed between 1 January 2011 and 31 December 2011 in the UK with data entered into the British Association of Urological Surgeons (BAUS) database, were identified for analysis. Overall surgical outcomes were assessed and subgroup analyses of these outcomes, based on operative technique [open RP (ORP), laparoscopic RP (LRP) and robot-assisted laparoscopic RP (RALP)], were made. Continuous variables were compared using the Mann-Whitney U-test and categorical variables using the Pearson chi-squared test. Univariate and multivariate binary regression analyses were performed to assess the effect of patient, surgeon and technique-related variables on surgical outcomes. RESULTS: During the study period 2163 RPs were performed by 115 consultants with a median (range) of 11 (1-154) cases/consultant. Most RPs were performed laparoscopically (ORP 25.8%, LRP 54.6%, RALP 19.6%) and those performing minimally invasive techniques are more likely to have a higher annual case volume with <1% ORP, 39% LRP and 62% RALP being performed by consultants with an annual caseload of >50 cases/year. Most patients were classified as having intermediate- or high-risk disease preoperatively (1596 patients, 82.5%) and this increased to 97.2% (1649) on postoperative risk stratification. The overall intraoperative complication rate was 14.2% and was significantly greater for LRP (17.8%) vs ORP (8.2%) and RALP (12.4%), (P < 0.001). In all, 71% of patients had an estimated blood loss (EBL) of <500 mL, although there were significantly more patients undergoing ORP with >500, > 1000 and >2000 mL EBL compared with the other techniques (P < 0.001). The postoperative complication rate was 10.7% overall, with a significantly greater postoperative complication rate in the LRP group (LRP 14.6%, ORP 8.8% and RALP 10.3% respectively, P = 0.007). Positive surgical margin (PSM) rates were 17.5% for pT2 disease and 42.3% for pT3 disease. The PSM rate was significantly lower in the RALP patients compared with the ORP patients for those with pT2 disease (P = 0.025), while there was no difference between ORP and LRP (ORP 21.7%, LRP 18.1% and RALP 13.0%). There was no significant difference in the PSM rate in pT3 disease between surgical techniques. CONCLUSION: Most RPs in the UK are performed using minimally invasive techniques, which offer reduced blood loss and transfusion rates compared with ORP. The operation time, complication rate, PSM rates, and association with higher volume practice support RALP as the minimally invasive technique of choice, which could have implications for regions without access to such services. The disparity in outcomes between this national study and high-volume single centres, most probably reflects the low median national case volume, and combined with the positive effect of high case volume on multivariate analysis of surgical outcomes and PSM rates, strengthens the argument for centralisation of services.

Matched-pair analysis of open versus laparoscopic nephroureterectomy for upper urinary tract urothelial cell carcinoma.

OBJECTIVE: Laparoscopic nephroureterectomy (LNU) offers a superior morbidity profile compared with open nephroureterectomy (ONU) in treating upper urinary tract urothelial cell carcinoma. Evidence of oncological equivalence between LNU and ONU is limited. We compare operative and oncological outcomes for LNU and ONU using matched-pair analysis. METHODS: Of 159 patients who underwent a nephroureterectomy at a single institution between April 1992 and April 2010, 13 pairs of ONU and LNU patients were matched for gender, age, tumour location, tumour grade and stage. Operative details, post-operative characteristics and recurrences were collated and survival rates analysed using the Kaplan-Meier method. RESULTS: There was no significant difference in mean operation time between LNU (191 min) and ONU (194 min, p=0.92). There was no significant difference in the 5-year survival rate between LNU and ONU (overall survival 59.1% vs. 73.5%, p=0.18; progression-free survival 24.0% vs. 56.0%, p=0.14; cancer-specific survival 60.9% vs. 73.5%, p=0.56; bladder cancer recurrence-free survival 8.7% vs. 0.0%, p=0.09). CONCLUSION: Amidst limited RCT and comparative studies, this study presents further evidence of oncological equivalence between LNU and ONU. There was a trend towards poorer outcomes following LNU though, which merits further study.

Five-year oncological outcomes of endoscopic extraperitoneal radical prostatectomy (EERPE) for prostate cancer: results from a medium-volume UK centre.

OBJECTIVE: To determine the 5-year oncological outcomes of endoscopic extraperitoneal radical prostatectomy (EERPE) from a medium-volume centre, thereby providing much needed data on outcomes from the UK. PATIENTS AND METHODS: From January 2006 to January 2012, 575 patients underwent EERPE for localized prostate cancer, performed by a single surgeon who had completed a modular training programme. Follow-up was as per local hospital policy and data were collected in our prospective database. A retrospective review of patient demographics, prostate-specific antigen (PSA) levels, pathological T stages, Gleason scores, surgical margin status and biochemical recurrence (BCR) data was performed. BCR was defined as PSA >0.2 µg/L. RESULTS: The mean (range) patient age was 62 (40.3-76.5) years and the mean (range) follow-up was 30 (12-72) months. The median (interquartile range [IQR]) operating time was 135 (120-170) min and the median (IQR) blood loss was 200 (100-250) mL. Of the 575 patients, 135 (23.5%) had positive surgical margins (PSMs). The PSM rate for pT2 disease was 66/406 patients (16.3%) and for pT3 disease it was 68/168 patients (40.5%). Overall BCR-free survival at 5-years was 81.5%. Multivariate Cox analysis showed that PSMs, Gleason score, D'Amico risk category and pT stage were independent predictors of BCR-free survival. CONCLUSIONS: This assessment of the oncological results of EERPE, which included the surgical learning curve, shows that the adoption of EERPE after mentored fellowship training translates into mid-term oncological outcomes in line with those of retropubic/transperitoneal laparoscopic approaches and with large-volume centres worldwide which have pioneered laparoscopic radical prostatectomy. The study shows that EERPE in a medium-volume second generation laparoscopic centre (that introduced EERPE after adequate training in pioneering centres) produces results with good 5-year oncological outcomes, similar to those of other major series, for patients in the UK.

Midterm oncological outcome and clinicopathological characteristics of anterior prostate cancers treated by endoscopic extraperitoneal radical prostatectomy.

PURPOSE: The purpose of the study is to characterise the clinicopathological characteristics of anterior prostate cancer (APC) compared to posterior prostate cancer (PPC)s and to determine the midterm oncological outcomes of patients with APCs undergoing endoscopic extraperitoneal radical prostatectomy (EERPE). METHODS: A retrospective review was carried out on all EERPEs performed in 2009. Pathology reports (transrectal ultrasound biopsy and surgical specimen), specimen photographs, demographic details and oncological outcome data from a prospectively maintained database were reviewed. Unpaired t test, chi-squared test and Kaplan-Meier curves were used for the analysis. RESULTS: Of 139 patients identified, 53 were APCs (38 %) and 86 were PPCs (62 %). Significantly, greater number of repeat biopsies were required to diagnose APCs (p = 0.02) and they had significantly fewer positive biopsy cores (p = 0.0005). The APC group had a significantly higher PSA density (PSAd) with (<5 and 5-25 %) tumour involvement in positive cores compared to PPCs (p = 0.036 and 0.024, respectively). APCs had higher positive surgical margin (PSM) rates (p = ns), the apical margin more likely positive than PPCs (p = 0.0006). Biochemical recurrence-free survival (BRFS) for APCs at 1, 2 and 3 years was lower than PPCs, although not statistically significant (p = 0.16). CONCLUSION: In our study, APCs proved more difficult to diagnose and stage, had a higher PSM rate and a trend towards a worse bRFS than PPCs. Additionally, the use of PSAd low core involvement biopsies might aide clinicians to investigate this cohort of patients more thoroughly before advising active surveillance.

Clinical utility of an epigenetic assay to detect occult prostate cancer in histopathologically negative biopsies: results of the MATLOC study.

PURPOSE: Concern about possible false-negative prostate biopsy histopathology findings often leads to rebiopsy. A quantitative methylation specific polymerase chain reaction assay panel, including GSTP1, APC and RASSF1, could increase the sensitivity of detecting cancer over that of pathological review alone, leading to a high negative predictive value and a decrease in unnecessary repeat biopsies. MATERIALS AND METHODS: The MATLOC study blindly tested archived prostate biopsy needle core tissue samples of 498 subjects from the United Kingdom and Belgium with histopathologically negative prostate biopsies, followed by positive (cases) or negative (controls) repeat biopsy within 30 months. Clinical performance of the epigenetic marker panel, emphasizing negative predictive value, was assessed and cross-validated. Multivariate logistic regression was used to evaluate all risk factors. RESULTS: The epigenetic assay performed on the first negative biopsies of this retrospective review cohort resulted in a negative predictive value of 90% (95% CI 87-93). In a multivariate model correcting for patient age, prostate specific antigen, digital rectal examination and first biopsy histopathological characteristics the epigenetic assay was a significant independent predictor of patient outcome (OR 3.17, 95% CI 1.81-5.53). CONCLUSIONS: A multiplex quantitative methylation specific polymerase chain reaction assay determining the methylation status of GSTP1, APC and RASSF1 was strongly associated with repeat biopsy outcome up to 30 months after initial negative biopsy in men with suspicion of prostate cancer. Adding this epigenetic assay could improve the prostate cancer diagnostic process and decrease unnecessary repeat biopsies.

Endoscopic versus laparoscopic management of noninvasive upper tract urothelial carcinoma: 20-year single center experience.

PURPOSE: We compare the outcomes of endoscopic surgery to laparoscopic nephroureterectomy for the management of specifically noninvasive upper tract urothelial carcinoma. MATERIALS AND METHODS: A retrospective database review identified consecutive patients with clinically noninvasive upper tract urothelial carcinoma who underwent endoscopic surgery (59, via ureteroscopic ablation or percutaneous resection) or laparoscopic nephroureterectomy (70) at a single center during 20 years (1991 to 2011). Overall survival, upper tract urothelial carcinoma specific survival, upper tract recurrence-free survival, intravesical recurrence-free survival, progression-free survival and renal unit survival were estimated using Kaplan-Meier methods, with differences assessed using the log rank test. RESULTS: Median age and followup were 74.8 years and 50 months, respectively. Overall renal preservation in the endoscopic group was high (5-year renal unit survival 82.5%), although this came at a cost of high local recurrence (endoscopic surgery 5-year recurrence-free survival 49.3%, laparoscopic nephroureterectomy 100%, p <0.0001). For G1 upper tract urothelial carcinoma, endoscopic surgery 5-year disease specific survival (100%) was equivalent to that of laparoscopic nephroureterectomy (100%). However, laparoscopic nephroureterectomy demonstrated superior disease specific survival to endoscopic surgery for G2 disease (91.7% vs 62.5%, p = 0.037) and superior progression-free survival for G3 disease (88.9% vs 55.6%, p = 0.033). CONCLUSIONS: For G1 upper tract urothelial carcinoma, endoscopic management can provide effective oncologic control and renal preservation. However, endoscopic management should not be considered for higher grade disease except in compelling imperative cases or in patients with poor life expectancy as oncologic outcomes are inferior to those of laparoscopic nephroureterectomy.

Locating and sizing tumor nodules in human prostate using instrumented probing - computational framework and experimental validation.

Detection of tumor nodules is key to early cancer diagnosis. This study investigates the potential of using the mechanical data, acquired from probing the prostate for detecting the existence, and, more importantly, characterizing the size and depth, from the posterior surface, of the prostate cancer (PCa) nodules. A computational approach is developed to quantify the uncertainty of nodule detectability and is based on identifying stiffness anomalies in the profiles of point force measurements across transverse sections of the prostate. The capability of the proposed method was assessed firstly using a 'training' dataset of in silico models including PCa nodules with random size, depth and location, followed by a clinical feasibility study, involving experimental data from 13 ex vivo prostates from patients who had undergone radical prostatatectomy. Promising levels of sensitivity and specificity were obtained for detecting the PCa nodules in a total of 44 prostate sections. This study has shown that the proposed methods could be a useful complementary tool to exisiting diagnostic methods of PCa. The future study will involve implementing the proposed measurement and detection strategies in vivo, with the help of a miniturized medical device.

Mechanical mapping of the prostate in vivo using Dynamic Instrumented Palpation; towards an in vivo strategy for cancer assessment.

A calibrated palpation sensor has been developed for making instrumented Digital Rectal Examinations (iDREs) with a view to assessing patients for prostate cancer. The instrument measures the dynamic stiffness of the palpable surface of the prostate, and has been trialled on 12 patients in vivo. The patients had been diagnosed with prostate cancer and were scheduled for radical prostatectomy. As far as possible, patients with asymmetric disease were chosen so as to give a variation in gland condition over the palpable surface. The device works by applying an oscillating pressure (force) to a flexible probe whose displacement into the tissue is also measured in order to yield a dynamic stiffness, the static stiffness being incidentally measured at the mean oscillatory force. The device was deployed mounted on the index finger of a urologist and measurements taken at 12-16 positions on each patient using light and firm pressure and palpation frequencies of 1 or 5 Hz. In parallel, conventional DRE assessments were made by a consultant urologist for cancer. After in vivo measurement, the glands were removed and examined histologically with each palpation point being classified as cancerous (C) or not (NC). The work has established the first measurements of static modulus of living prostate tissue to be: 26.8 (13.3) kPa for tissue affected by prostate cancer (C classification), and 24.8 kPa (11.9) for tissue unaffected by cancer (NC classification), values quoted as median (interquartile range). The dynamic properties were characterised by: dynamic modulus, 5.15 kPa (4.86) for the C classification and 4.61 kPa (3.08) for the NC classification and the time lag between force and displacement at 5 Hz palpation frequency, 0.0175 s (0.0078) for the C classification and 0.0186 s (0.0397) for the NC classification, values again quoted as median (interquartile range). With the limited set of features that could be generated, an Artificial Neural Network (ANN) classification yielded a sensitivity of 97%, negative predictive value of 86%, positive predictive value of 67% and accuracy of 70% but with relatively poor specificity (30%). Besides extending the feature set, there are a number of changes in probe design, probing strategy and in mechanics analysis, which are expected to improve the diagnostic capabilities of the method.

The operative safety and oncological outcomes of laparoscopic nephrectomy for T3 renal cell cancer.

UNLABELLED: What's known on the subject? and What does the study add? Laparoscopic radical nephrectomy is a well established treatment for localized RCC, where nephron-sparing approaches are not appropriate. As surgeon and departmental experience grow more extensive tumours will be tackled laparoscopically. However, little is known about the operative safety and oncological outcomes of the laparoscopic approach for locally advanced RCC. The present study describes the largest reported cohort of patients receiving laparoscopic radical nephrectomy for locally advanced RCC. In the context of suitably experienced personnel in an established centre, we have established that this approach is safe from operative, postoperative and oncological standpoints, with comparable data to existing open series. OBJECTIVE: To determine the operative, postoperative and oncological outcomes of laparoscopic radical nephrectomy (LRN) for locally advanced renal cell cancer (RCC), which, as surgeon and departmental experience increases, is being performed more often. PATIENTS AND METHODS: In total, 94 consecutive patients receiving LRN for pathologically confirmed T3 or T4 RCC at a tertiary referral centre between March 2002 and May 2010 were analyzed. Preoperative, operative, tumour and postoperative characteristics were evaluated together with recurrence and outcome data. Survival was estimated using the Kaplan-Meier method. Cox's proportional hazards model was used for multivariate analysis. RESULTS: In total, 77 patients had LRN with curative intent and 17 patients had LRN with cytoreductive intent. There were six LRNs (6.4%) that were converted to open procedures. Overall, there were two (2.1%) Clavien grade IIIa complications, one (1.1%) grade IVa complication and one (1.1%) postoperative death. Overall median follow-up was 17.4 months. In total, 22 (28.6%) patients receiving curative LRN developed a recurrence after a median of 13.9 months; 12 (54.5%) patients developed distant metastases, five (22.7%) patients had local recurrences and three (13.6%) patients had transcoelomic spread. Median predicted progression free survival was 48.4 months in patients undergoing LRN with curative intent. Median predicted overall survival was 65.6 months after curative LRN and 15.7 months after cytoreductive LRN. Multivariate analysis did not reveal any variables influencing recurrence or survival. CONCLUSIONS: In the context of suitably experienced personnel in an established centre, LRN for locally advanced RCC is safe from an operative and oncological standpoint. Patients clinically staged as T3 RCC must still be selected carefully for LRN in a multidisciplinary setting.

CD4+ and CD8+ T-lymphocyte scores cannot reliably predict progression in patients with benign prostatic hyperplasia.

OBJECTIVE: To determine whether the density of CD4(+) and CD8(+) T-lymphocytes in a transrectal ultrasonography (TRUS) biopsy of the prostate can be used to predict the progression of lower urinary tract symptoms (LUTS) in benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: In total, 100 patients were randomly selected from a pool of patients with histologically proven, benign TRUS biopsy specimens. There were seven full years of follow-up available. Clinical data were recorded, including prostate volume, International Prostate Symptom Score (IPSS), prostate-specific antigen, urine flow rate, postvoid residual urine volume and previous prostate surgery. Markers of disease progression included the subsequent development of acute urinary retention (AUR), ≥4 point rise in IPSS, prescription of medical therapy (α-blocker or 5-α-reductase inhibitor) and bladder outlet surgery. Four patients' specimens were unsuitable for analysis. Biopsy sections from 96 patients were immunohistochemically stained for the presence of CD4(+) and CD8(+) T-lymphocytes and the density of infiltrate was assessed using random field sampling and point counting. RESULTS: Some 29% of patients (28/96) did not have BPH at the time of biopsy. Of all patients, 41% (39/96) progressed, 10% of whom (4/39) did not have BPH at the time of biopsy. A further 10% (10/96) developed AUR, 7% (7/96) had a ≥4 point rise in IPSS, 33% (32/96) required medical therapy for BPH and 11% (11/96) required bladder outlet surgery. There was low correlation between CD4(+) and CD8(+) densities in paired sections. CD4(+) and CD8(+) densities did not provide any significant predictive function in the progression of BPH, nor was their any predictive association noted between CD4(+) and CD8(+) scores and the development of prostate cancer. Sub-analysis did show that a threshold mean of ≥1.35 CD8(+) cells per field predicted progression to AUR with a sensitivity of 60% (95% confidence interval, CI, 26.2-87.8), specificity of 73.3% (95% CI 62.6-82.2) but a positive predictive value of 20.6% (95% CI 8.0-39.7). CD4(+) infiltrate density suggested a trend to general progression but without statistical significance. CONCLUSION: The present study, despite certain trends, shows no evidence for an association between CD4(+) and CD8(+) T-lymphocytes and the progression of LUTS in BPH.

Functional and oncological outcomes of men under 60 years of age having endoscopic surgery for prostate cancer are optimal following intrafascial endoscopic extraperitoneal radical prostatectomy.

BACKGROUND: Endoscopic extraperitoneal radical prostatectomy (EERPE) is a well-established procedure for treatment of prostate cancer (PCa). Intrafascial nerve-sparing EERPE (nsEERPE) aims to preserve the neurovascular bundle and subsequently erectile function. This study assessed the functional and oncological outcomes of nsEERPE with particular regard to younger patients. METHODS: Data on 353 men undergoing EERPE between February 2006 and December 2009 was collected prospectively. Non-nerve-sparing EERPE was performed in men diagnosed with PCa with a Gleason score >6 and/or PSA >10 µg/l. nsEERPE was undertaken in men diagnosed PCa with PSA ≤10 µg/l and Gleason score ≤6. Biochemical failure (BF) was defined as PSA ≥0.2 µg/l after nadir or never reached nadir. Men were deemed continent if dry or using 1 confidence pad. Erections satisfactory for intercourse (ESI) or unsatisfactory for intercourse (EUI) were recorded. RESULTS: 102 Men (29%) had nsEERPE and 126 (36%) EERPE. pT2 positive surgical margin (PSM) rates were 20.5% for nsEERPE and 21.3% for EERPE (P = 1). Continence rates following nsEERPE were 59%, 86%, 97% and 52%, 76%, 86% following EERPE at 3, 6 and 12 months of follow-up respectively (P > 0.05). Erectile function rates for nsEERPE were 24%, 52%, 71% compared to 6%, 14%, 29% for EERPE at 3, 6 and 12 months respectively (P < 0.001). Erectile function in men <60 y having nsEERPE was 75% at 12 months. CONCLUSIONS: Continence returned more rapidly and erectile function was improved following nsEERPE vs. EERPE. These results suggest that nsEERPE can be performed with particularly good oncological and functional outcome in <60 y men.

A novel method for rapid and quantitative mechanical assessment of soft tissue for diagnostic purposes: A computational study.

Biological tissues often experience drastic changes in their microstructure due to their pathophysiological conditions. Such microstructural changes could result in variations in mechanical properties, which can be used in diagnosing or monitoring a wide range of diseases, most notably cancer. This paves the avenue for non-invasive diagnosis by instrumented palpation although challenges remain in quantitatively assessing the amount of diseased tissue by means of mechanical characterization. This paper presents a framework for tissue diagnosis using a quantitative and efficient estimation of the fractions of cancerous and non-cancerous tissue without a priori knowledge of tissue microstructure. First, the sample is tested in a creep or stress relaxation experiment, and the behavior is characterized using a single term Prony series. A rule of mixtures, which relates tumor fraction to the apparent mechanical properties, is then obtained by minimizing the difference between strain energy of a heterogeneous system and an equivalent homogeneous one. Finally, the percentage of each tissue constituent is predicted by comparing the observed relaxation time with that calculated from the rule of mixtures. The proposed methodology is assessed using models reconstructed from histological samples and magnetic resonance imaging of prostate. Results show that estimation of cancerous tissue fraction can be obtained with a maximum error of 12% when samples of different sizes, geometries, and tumor fractions are presented. The proposed framework has the potential to be applied to a wide range of diseases such as rectal polyps, cirrhosis, or breast and prostate cancer whose current primary diagnosis remains qualitative.

Dynamic instrumented palpation - a new method for soft tissue quality assessment: application to prostate disease diagnosis.

The objective is to establish the feasibility of using dynamic instrumented palpation, a novel technique of low-frequency mechanical testing, applied here to diagnose soft tissue condition. The technique is applied, in vitro, to samples of excised prostate gland affected by benign prostate hyperplasia and/or prostate cancer. Particular attention is paid to the relationship between the histological structure of the tissue and the dynamic mechanical properties in an attempt to separate patient-specific aspects from histopathological condition (i.e. prostate cancer or benign prostate hyperplasia). The technique is of clinical interest because it is potentially deployable in vivo. Prostate samples were obtained from a total of 36 patients who had undergone transurethral resection of the prostate to relieve prostatic obstruction and 4 patients who had undergone radical cystoprostatectomy for bladder cancer. Specimens (chips) recovered from transurethral resection of the prostate were of nominal size 5 mm × 8 mm and thicknesses between 2 and 4 mm, whereas those from the cystoprostatectomy were in the form of transverse slices of thickness approximately 6 mm. Specimens were mechanically tested by a controlled strain cyclic compression technique, and the resulting dynamic mechanical properties expressed as the amplitude ratio and phase difference between the cyclic stress and cyclic strain. After mechanical testing, the percentage areas of glandular and smooth muscle were measured at each probe point. Good contrast between the dynamic modulus of chips from benign prostate hyperplasia and prostate cancer patients was demonstrated, and absolute values similar to those published by other authors are reported. For the slices, modulus values were considerably higher than for chips, and good in-patient mechanical contrast was revealed for predominantly nodular and predominantly stromal areas. Extending this classification between patients required pattern recognition techniques. Overall, the study has demonstrated that dynamic mechanical properties can potentially be used for diagnosis of prostate condition using in vivo measurements.

Histology-based homogenization analysis of soft tissue: application to prostate cancer.

It is well known that the changes in tissue microstructure associated with certain pathophysiological conditions can influence its mechanical properties. Quantitatively relating the tissue microstructure to the macroscopic mechanical properties could lead to significant improvements in clinical diagnosis, especially when the mechanical properties of the tissue are used as diagnostic indices such as in digital rectal examination and elastography. In this study, a novel method of imposing periodic boundary conditions in non-periodic finite-element meshes is presented. This method is used to develop quantitative relationships between tissue microstructure and its apparent mechanical properties for benign and malignant tissue at various length scales. Finally, the inter-patient variation in the tissue properties is also investigated. Results show significant changes in the statistical distribution of the mechanical properties at different length scales. More importantly the loss of the normal differentiation of glandular structure of cancerous tissue has been demonstrated to lead to changes in mechanical properties and anisotropy. The proposed methodology is not limited to a particular tissue or material and the example used could help better understand how changes in the tissue microstructure caused by pathological conditions influence the mechanical properties, ultimately leading to more sensitive and accurate diagnostic technologies.

Quantitative mechanical assessment of the whole prostate gland ex vivo using dynamic instrumented palpation.

An instrumented palpation sensor, designed for measuring the dynamic modulus of tissue in vivo, has been developed and trialled on ex vivo whole prostate glands. The sensor consists of a flexible membrane sensor/actuator with an embedded strain gauge and is actuated using a dynamically varying airflow at frequencies of 1 and 5 Hz. The device was calibrated using an indentation stiffness measurement rig and gelatine samples with a range of static modulus similar to that reported in the literature for prostate tissue. The glands were removed from patients with diagnosed prostate cancer scheduled for radical prostatectomy, and the stiffness was measured within 30 min of surgical removal. Each prostate was later examined histologically in a column immediately below each indentation point and graded into one of the four groups; normal, benign prostatic hyperplasia, cancerous and mixed cancer and benign prostatic hyperplasia. In total, 11 prostates were assessed using multiple point probing, and the complex modulus at 1 and 5 Hz was calculated on a point-by-point basis. The device yielded values of quasi-static modulus of 15 ± 0.5 kPa and dynamic modulus of 20 ± 0.5 kPa for whole prostates, and a sensitivity of up to 80% with slightly lower specificity was achieved on diagnosis of prostate cancer using a combination of mechanical measures. This assessment did not take into account some obvious factors such as edge effects, overlap and clinical significance of the cancer, all of which would improve performance. The device, as currently configured, is immediately deployable in vivo. A number of improvements are also identified which could improve the sensitivity and specificity in future embodiments of the probe.

Patient specific modeling of palpation-based prostate cancer diagnosis: effects of pelvic cavity anatomy and intrabladder pressure.

Computational modeling has become a successful tool for scientific advances including understanding the behavior of biological and biomedical systems as well as improving clinical practice. In most cases, only general models are used without taking into account patient-specific features. However, patient specificity has proven to be crucial in guiding clinical practice because of disastrous consequences that can arise should the model be inaccurate. This paper proposes a framework for the computational modeling applied to the example of the male pelvic cavity for the purpose of prostate cancer diagnostics using palpation. The effects of patient specific structural features on palpation response are studied in three selected patients with very different pathophysiological conditions whose pelvic cavities are reconstructed from MRI scans. In particular, the role of intrabladder pressure in the outcome of digital rectal examination is investigated with the objective of providing guidelines to practitioners to enhance the effectiveness of diagnosis. Furthermore, the presence of the pelvic bone in the model is assessed to determine the pathophysiological conditions in which it has to be modeled. The conclusions and suggestions of this work have potential use not only in clinical practice and also for biomechanical modeling where structural patient-specificity needs to be considered. © 2015 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.