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.

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.

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.

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.

Tissue quality assessment using a novel direct elasticity assessment device (the E-finger): a cadaveric study of prostatectomy dissection.

INTRODUCTION: Minimally invasive radical prostatectomy (RP) (robotic and laparoscopic), have brought improvements in the outcomes of RP due to improved views and increased degrees of freedom of surgical devices. Robotic and laparoscopic surgeries do not incorporate haptic feedback, which may result in complications secondary to inadequate tissue dissection (causing positive surgical margins, rhabdosphincter damage, etc). We developed a micro-engineered device (6 mm2 sized) [E-finger]) capable of quantitative elasticity assessment, with amplitude ratio, mean ratio and phase lag representing this. The aim was to assess the utility of the device in differentiating peri-prostatic tissue types in order to guide prostate dissection. MATERIAL AND METHODS: Two embalmed and 2 fresh frozen cadavers were used in the study. Baseline elasticity values were assessed in bladder, prostate and rhabdosphincter of pre-dissected embalmed cadavers using the micro-engineered device. A measurement grid was created to span from the bladder, across the prostate and onto the rhabdosphincter of fresh frozen cadavers to enable a systematic quantitative elasticity assessment of the entire area by 2 independent assessors. Tissue was sectioned along each row of elasticity measurement points, and stained with haematoxylin and eosin (H&E). Image analysis was performed with Image Pro Premier to determine the histology at each measurement point. RESULTS: Statistically significant differences in elasticity were identified between bladder, prostate and sphincter in both embalmed and fresh frozen cadavers (p = < 0.001). Intra-class correlation (ICC) reliability tests showed good reliability (average ICC = 0.851). Sensitivity and specificity for tissue identification was 77% and 70% respectively to a resolution of 6 mm2. CONCLUSIONS: This cadaveric study has evaluated the ability of our elasticity assessment device to differentiate bladder, prostate and rhabdosphincter to a resolution of 6 mm2. The results provide useful data for which to continue to examine the use of elasticity assessment devices for tissue quality assessment with the aim of giving haptic feedback to surgeons performing complex surgery.

Exploring the feasibility and acceptability of couple-based psychosexual support following prostate cancer surgery: study protocol for a pilot randomised controlled trial.

BACKGROUND: Men who undergo surgery for prostate cancer frequently experience significant side-effects including urinary and sexual dysfunction. These difficulties can lead to anxiety, depression and reduced quality of life. Many partners also experience psychological distress. An additional impact can be on the couple relationship, with changes to intimacy, and unmet psychosexual supportive needs in relation to sexual recovery and rehabilitation. The aim of this exploratory randomised controlled trial pilot study is to determine the feasibility and acceptability of a novel family-relational-psychosexual intervention to support intimacy and reduce distress among couples following prostate cancer surgery and to estimate the efficacy of this intervention. METHODS/DESIGN: The intervention will comprise six sessions of psychosexual and relationship support delivered by experienced couple-support practitioners. Specialist training in delivering the intervention will be provided to practitioners and they will be guided by a detailed treatment manual based on systemic principles. Sixty-eight couples will be randomised to receive either the intervention or standard care (comprising usual follow-up hospital appointments). A pre-test, post-test design will be used to test the feasibility of the intervention (baseline, end of intervention and six-month follow-up) and its acceptability to couples and healthcare professionals (qualitative interviews). Both individual and relational outcome measures will assess sexual functioning, anxiety and depression, couple relationship, use of health services and erectile dysfunction medication/technologies. An economic analysis will estimate population costs of the intervention, compared to usual care, using simple modelling to evaluate the affordability of the intervention. DISCUSSION: Given the increasing incidence and survival of post-operative men with prostate cancer, it is timely and appropriate to determine the feasibility of a definitive trial through a pilot randomised controlled trial of a family-relational-psychosexual intervention for couples. The study will provide evidence about the components of a couple-based intervention, its acceptability to patients and healthcare professionals, and its influence on sexual and relational functioning. Data from this study will be used to calculate sample sizes required for any definitive trial. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01842438.Registration date: 24 April 2013; Randomisation of first patient: 13 May 2013.