Transarterial ethiodised oil marking before CT-guided renal cryoablation: evaluation of tumour visibility in various renal cell carcinoma subtypes.

AIM: To evaluate ethiodised oil retention of transarterial embolisation using ethiodised oil (ethiodised oil marking) before computed tomography (CT)-guided percutaneous cryoablation (PCA) according to renal cell carcinoma (RCC) subtype. MATERIALS AND METHODS: Ethiodised oil marking was performed 1-3 days before PCA in 99 patients with 99 RCCs from 2016 to 2020. Ethiodised oil retention on CT images was evaluated retrospectively and CT attenuation values in the tumour were measured. Regions of interest (ROI) were placed on the tumours to calculate: average (ROI-average), maximal (ROI-max), minimum (ROI-min), and standard deviation (ROI-SD). Qualitative scores comprising a five-point scale (5, excellent; 1, poor) were evaluated for the retention scores (RS) of ethiodised oil in the tumour (ethiodised oil-RS) and the visualisation scores (VS) of the boundary between the tumour and renal parenchyma (boundary-VS). RESULTS: The histological subtypes comprised clear cell (ccRCC; n=85), papillary (pRCC; n=6), and chromophobe/oncocytoma renal cell carcinoma (chrRCC; n=8). The mean ROI-average, ROI-max, and ROI-SD were significantly higher in ccRCCs than in chrRCCs and pRCCs (p<0.05). The mean ethiodised oil-RS was significantly lower in pRCCs than in ccRCCs (p=0.039), and the mean boundary-VS was >4 in all subtypes. Even with poor intratumour ethiodised oil retention (n=6), sufficient boundary-VS was obtained due to "inverted marking." All PCA procedures were completed without additional intravenous contrast material injection at the time of PCA. CONCLUSION: Regardless of the tumour subtypes, ethiodised oil marking aids in visualising the boundary between the tumour and parenchyma on non-contrast CT in PCA.

[Interest using 3D ultrasound and MRI fusion biopsy for prostate cancer detection]. / Quel est l'intérêt de l'échographie 3D et fusion d'image IRM pour la détection du cancer de la prostate ?

INTRODUCTION: The strategic therapy for prostate cancer depends on histo-pronostics data, which could be upgraded by obtaining targeted biopsies (TB) with MRI (magnetic resonance imagery) fusion 3D ultrasound. OBJECTIVES: To compare diagnostic yield of image fusion guided prostate biopsy using image fusion of multi-parametric MRI (mpMRI) with 3D-TRUS. MATERIALS AND METHODS: Between January 2010 and April 2013, 179 consecutive patients underwent outpatient TRUS biopsy using the real-time 3D TRUS tracking system (Urostation™). These patients underwent MRI-TRUS fusion targeted biopsies (TB) with 3D volume data of the MRI elastically fused with 3D TRUS at the time of biopsy. RESULTS: A hundred and seventy-three patients had TBs with fusion. Mean biopsy core per patient were 11.1 (6-14) for SB and 2.4 (1-6) for TB. SBs were positive in 11% compared to 56% for TB (P<0.001). TB outperformed systematic biopsy(SB) in overall any cancer detection rate, detection of clinically significant cancer (58% vs. 36%), cancer core length (6.8mm vs. 2.8mm), and cancer rate per core (P<0.001). In multivariable logistic regression, with TB we have more chance to find a clinically significant cancer (OR:3.72 [2-6.95]). When both TRUS and MRI are positive, there is 2.73 more chance to find a clinically significant cancer. CONCLUSION: MR/TRUS elastic fusion-guided biopsies outperform systematic random biopsies in diagnosing clinically significant cancer. Ability of interpretation of real-time TRUS is essential to perform the higher level of MR/US fusion and should be use for active surveillance. LEVEL OF PROOF: 4.

Standardization of definitions in focal therapy of prostate cancer: report from a Delphi consensus project.

PURPOSE: To reach standardized terminology in focal therapy (FT) for prostate cancer (PCa). METHODS: A four-stage modified Delphi consensus project was undertaken among a panel of international experts in the field of FT for PCa. Data on terminology in FT was collected from the panel by three rounds of online questionnaires. During a face-to-face meeting on June 21, 2015, attended by 38 experts, all data from the online rounds were reviewed and recommendations for definitions were formulated. RESULTS: Consensus was attained on 23 of 27 topics; Targeted FT was defined as a lesion-based treatment strategy, treating all identified significant cancer foci; FT was generically defined as an anatomy-based (zonal) treatment strategy. Treatment failure due to the ablative energy inadequately destroying treated tissue is defined as ablation failure. In targeting failure the energy is not adequately applied to the tumor spatially and selection failure occurs when a patient was wrongfully selected for FT. No definition of biochemical recurrence can be recommended based on the current data. Important definitions for outcome measures are potency (minimum IIEF-5 score of 21), incontinence (new need for pads or leakage) and deterioration in urinary function (increase in IPSS >5 points). No agreement on the best quality of life tool was established, but UCLA-EPIC and EORTC-QLQ-30 were most commonly supported by the experts. A complete overview of statements is presented in the text. CONCLUSION: Focal therapy is an emerging field of PCa therapeutics. Standardization of definitions helps to create comparable research results and facilitate clear communication in clinical practice.

Follow-up modalities in focal therapy for prostate cancer: results from a Delphi consensus project.

INTRODUCTION: Focal therapy can offer the middle ground for treatment between active surveillance and radical therapy in patients with low- and intermediate-risk prostate cancer. Factors that prohibit focal therapy from being standard of care are numerous. Several consensus projects have been conducted to position the utilization of imaging and trial design in focal therapy. However, the literature is still scarce on patient follow-up after focal therapy. For these reasons, an international multidisciplinary consensus project was established in order to reach consensus about a uniform follow-up protocol after focal therapy. OBJECTIVE: To standardize patient follow-up after focal therapy. MATERIALS AND METHODS: A literature study was performed, and a questionnaire was constructed. The questionnaire was sent out to 76 participants (70 % urologists, 28 % radiologists and 2 % biomedical engineers) in three consecutive rounds according to the Delphi method. In each round, the panelists were presented with the results of the previous round. Participants each had the opportunity to adapt, delete or add questions. The topics discussed pertaining to follow-up after focal therapy were as follows: (1) general,(2) biopsies, (3) PSA, (4) digital rectal examination (DRE), (5) imaging, (6) quality of life (QoL) and (7) registration and pooling of data. The project was concluded with a face-to-face meeting in which final conclusions were formulated. RESULTS: The follow-up after focal therapy should be a minimum of 5 years. The following modalities should be included in assessing post-treatment outcomes: multiparametric MRI (mpMRI), biopsies, assessment of erectile function, QoL, urinary symptoms and incontinence. A systematic 12-core TRUS biopsy combined with 4-6 targeted biopsy cores of the treated area and any suspicious lesion(s) should be performed after 1 year, and thereafter only when there is suspicion on imaging. The ideal way to perform targeted biopsies is to use TRUS-MRI fusion technology. PSA should be performed for research purposes, in the first year, every 3 months, and after the first year, every 6 months. mpMRI is the optimal imaging modality for follow-up after focal therapy. On a 1.5T scanner, an endorectal coil is strongly advised by the panel, whereas on a 3T machine, it is optional, however, it will improve image quality. The following sequences should be included: T2WI, DWI including high b values of >1,000 and ADC maps of DWI, DCE and T1WI. Imaging should be performed at 6 months and at 1 year following treatment; after the first year post-treatment, it should be performed every year until 5 years following treatment. All data should ideally be pooled in a common global database. CONCLUSION: Focal therapy is a relatively new form of treatment for prostate cancer. In order to include focal therapy as a standard of care treatment, consistent follow-up is necessary. By implementing the results of this consensus study, focal therapy users will be able to provide important and standardized outcome data.

Safety and efficacy of PD-1/PD-L1 blockade in patients with preexisting antinuclear antibodies.

PURPOSE: Immune checkpoint inhibitors (ICIs) show promising clinical activity in advanced cancers. However, the safety and efficacy of PD-1/PD-L1 blockade in patients with preexisting antinuclear antibodies (ANA) are unclear. METHODS: 191 patients treated with nivolumab, pembrolizumab, atezolizumab, or durvalumab for unresectable advanced cancers between September 2014 and December 2018 were identified retrospectively. Patients were divided into positive (ANA titers ≥ 1:160) and negative ANA groups (ANA titers < 1:160). Development of immune-related adverse events (irAEs), the overall response rate (ORR), and disease control rate (DCR) were monitored. RESULTS: Positive ANA titers were seen in 9 out of 191 patients. Four patients in the positive ANA group and 69 patients in the negative group developed irAEs of any grade without a significant difference between the groups. The development of endocrine, pulmonary, and cutaneous irAEs was not significant, whereas positive ANA was significantly higher in patients who developed colitis (2/9) than in patients who did not (3/182, P = 0.0002). DCR in the positive and negative ANA group was 37.5% and 67.5%, respectively, and was not statistically significant, but had better efficacy in patients without ANA (P = 0.08). ANA-related autoimmune diseases such as SLE, Sjögren's syndrome, MCTD, scleroderma, dermatomyositis, and polymyositis was not induced in either group. However, one patient with preexisting dermatomyositis had a flare up after initiation of atezolizumab. CONCLUSION: Further studies to identify predictive factors for the development of irAEs are required to provide relevant patient care and maximize the therapeutic benefits of ICIs.

The significance of dihydropyrimidine dehydrogenase (DPD) activity in bladder cancer.

Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme in the pathway of uracil and thymine catabolism. DPD is also the principal enzyme involved in the degradation of 5-fluorouracil (5-FU), which is one of the anticancer chemotherapeutic agents currently used in the treatment of bladder cancer. Little is known about the significance of DPD activity in human cancers. We investigated the activity of DPD in 74 bladder cancers and the relationship between the DPD activity and the sensitivity to 5-FU. The levels of DPD activity in bladder cancer and normal bladder tissues were determined by the 5-FU degradation assay. The sensitivity to 5-FU was assessed by the microculture tetrazolium dye (dimethylthiazolyl-2-5-diphenyltetrazolium bromide; MTT) assay. The activity of DPD was approximately 2-fold higher in bladder cancer tissues compared with normal bladder tissues. DPD activity in invasive bladder cancers was approximately 2-fold higher than that in superficial cancers. In addition, the levels of DPD activity in grade 2 and grade 3 bladder cancers were approximately 3-fold and 4-fold higher than that in grade 1 cancers, respectively. Patients with superficial bladder cancer with a low DPD activity had a slightly longer postoperative tumour-free period than those with a high DPD activity over a 2-year follow-up period, but this was not significant. There was an inverse correlation between DPD activity in bladder cancer cells and their sensitivity to 5-FU. Furthermore, 5-chloro-2,4-dihydroxypyridine (CDHP), a potent DPD inhibitor, enhanced the sensitivity to 5-FU. The present study has demonstrated that the level of DPD activity correlated with the progression of the stage and an increase in the grade of the bladder cancer. These results suggest that an elevated DPD activity might be associated with the malignant potential of the bladder cancer. In addition, it might be possible to overcome 5-FU insensitivity by using DPD inhibitors in the treatment protocols of 5-FU-based chemotherapy for bladder cancers.

Role of PSA and its indices in determining the need for repeat prostate biopsies.

OBJECTIVES: To retrospectively study evaluated prostate-specific antigen (PSA) and four PSA indices as criteria for performing a repeat biopsy when the initial biopsy findings are negative for cancer. METHODS: One, two, or more repeat biopsy sessions were performed on 193, 54, and 14 men, respectively, all of whom had an initially negative biopsy at our institution. We compared the usefulness of PSA, PSA density, age-referenced PSA, volume-referenced PSA, and PSA velocity for predicting the presence of cancer. RESULTS: Overall, 51 men (26%) were found to have cancer on repeat biopsy. Cancer was found in 17% (33 of 193) of the men on the first repeat biopsy and 26% (14 of 54) of the men who had a second repeat biopsy. Of all the indices, PSA and volume-referenced PSA had the highest sensitivity, missing the fewest cancers; however, this was achieved at the expense of saving the least number of biopsies. We evaluated the usefulness of indices among 9 patients who had a normal PSA at the initial biopsy; volume-referenced PSA was the earliest predictive index indicating that a repeat biopsy be performed. Analysis of the area under the receiver-operating characteristic curves revealed no significant advantage for any index over PSA alone in determining who should undergo a repeat biopsy. CONCLUSIONS: In determining the need for repeat biopsies, the established PSA threshold value of 4 ng/mL is equivalent or superior to age-referenced PSA, volume-referenced PSA, PSA density, and PSA velocity. However, volume-referenced PSA has the potential to be the earliest index predicting cancer in men with normal PSA level.

Correlation of presumed circle area ratio with infravesical obstruction in men with lower urinary tract symptoms.

OBJECTIVES: To examine the predictive value of ultrasonic measurements obtained by transrectal ultrasonography for infravesical obstruction as evaluated by pressure flow studies. METHODS: In 85 men with moderate to severe lower urinary tract symptoms, ultrasonic measurements including prostatic volume, transition zone volume, transition zone index (transition zone volume/prostatic volume), and presumed circle area ratio (PCAR) were compared with urodynamic parameters obtained by pressure flow studies. RESULTS: There were significant interrelationships between these ultrasonic measurements, which were all significantly greater in the obstructed patients than in the unobstructed patients. A simple regression analysis demonstrated that prostatic volume (r = 0.362, P < 0.001), transition zone volume (r = 0.373, P < 0.0005), transition zone index (r = 0.331, P < 0.005), and PCAR (r = 0.487, P < 0.0001) correlated significantly with the Abrams-Griffiths number. More importantly, a multiple regression analysis demonstrated PCAR to be the only independent determinant of the Abrams-Griffiths number. A receiver operator characteristics curve analysis showed that 0.8 was the most suitable cutoff value of PCAR for the prediction of infravesical obstruction with a diagnostic accuracy of 76.5%. CONCLUSIONS: PCAR is useful as a transrectal ultrasonic measurement in assessing the severity of infravesical obstruction in men with lower urinary tract symptoms.

Ultrasonic estimation of bladder weight as a measure of bladder hypertrophy in men with infravesical obstruction: a preliminary report.

The aim of the present study was to evaluate the usefulness of ultrasonic estimation of bladder weight as a measure of bladder hypertrophy using transabdominal ultrasonography in men with infravesical obstruction. Ultrasonically estimated bladder weight (UEBW) was calculated from the thickness of the bladder wall measured ultrasonically and the intravesical volume at the ultrasonic measurement, assuming a spheric bladder. There was a statistically significant correlation (r = 0.970, P <0.001) between the actual bladder weight of cadaver bladders and the UEBW. The UEBW did not change with bladder filling. The UEBW in the obstructed group (group O, 49.7 +/- 19.5 g, mean +/- SD) was significantly greater than that in the normal control group (group NC, 25.6 +/- 5.7 g; P <0.001) or the nonobstructed group (group NO, 28.4 +/- 4.2 g; P <0.001). The greatest UEBW was 34.8 g in group NC and 35.2 g in group NO, whereas 94% (45 of 48) of group O had a UEBW greater than 35.0 g. In all 5 patients with benign prostatic hyperplasia (BPH), the increased UEBW decreased to a normal control level at 3 months after treatment of BPH. This new noninvasive method may be useful in investigation of bladder hypertrophy.

Significant decrease of the International Index of Erectile Function in male renal failure patients treated with hemodialysis.

In order to evaluate the erectile function in male renal failure patients treated with hemodialysis (HD), we investigated the International Index of Erectile Function (IIEF) in patients and healthy controls. The subjects were 174 male patients treated with HD, of whom 43 had diabetes mellitus (DM) and the remaining 131 patients did not have DM. The controls were 1133 healthy males. We evaluated the prevalence of erectile dysfunction (ED) using the erectile function (EF) score, which is one of the five domains of the IIEF, in each age group (upto 39 y old, 40-49 y old, 50-59 y old, 60-69 y old). The severity of ED was classified into five categories using EF in each age group. The univariate logistic regression analysis and multiple variate analysis of IIEF in HD patients were performed. The prevalence of ED in HD patients was significantly higher than that in the controls in each age group. The severity of ED in HD patients was also significantly higher than that in the controls in each age group. In the logistic regression analysis and multiple variate analysis of IIEF in HD patients, DM and age were significant risk factors on sexual dysfunction. ED was more prevalent in male renal failure patients treated with HD than in the controls. In the patient group, ED was more prevalent in older DM patients.

Significant changes in transrectal ultrasonic measurements of the prostate in relation to the degree of rectal wall distension.

The present study was conducted to reveal the possible changes in transrectal ultrasonic measurements of the prostate in relation to the degree of rectal wall distension. When analyzed together for 51 men, all measurements but area changed statistically significantly as the rectal wall was distended by a balloon covering a probe. Ultrasonic measurements concerning the prostatic shape changed more remarkably than those concerning its size. More importantly, changes in ultrasonic measurements were much more remarkable in patients with a healthy prostate than in those with an advanced BPH. These results suggest that possible changes in prostatic shape with the rectal wall distension has to be taken into account when evaluating transrectal prostatic ultrasonograms in terms of changes in shape, especially in patients with a healthy prostate. This is also the case when the diagnosis of BPH is made based on the change in shape, such as presumed circle area ratio, which is a parameter representing the roundness of the horizontal sonogram of the prostate.

Intraobserver and interobserver variance in the measurement of ultrasound-estimated bladder weight.

Recently, we reported that ultrasound-estimated bladder weight (UEBW) could be used as a noninvasive tool in evaluating the degree of bladder hypertrophy. This study was designed to test the reproducibility of its measurement. The overall mean UEBW of the initial measurement and that of the second one by one observer in 36 cases was 42.8 +/- 22.6 g and 42.9 +/- 22.6 g, respectively. The paired differences between two measurements ranged from -3.4 to 2.7 g, with a mean difference of only -0.1 g. The interobserver variance was also slight. The paired differences between UEBW measurements derived from the two observers in 32 cases ranged from -6.0 to 7.9 g, with a mean difference of only 0.1 g. The Cochran's test statistic of the measurements of UEBW was 0.142 for one observer and 0.130 for two, which were less than its 5% critical value. Due to these favorable characteristics, UEBW could be reliable tool for the investigation of bladder hypertrophy with a sufficient reproducibility.

Preliminary results of power Doppler imaging in benign prostatic hyperplasia.

Power Doppler imaging was performed in 77 patients with lower urinary tract symptoms to characterize Doppler blood-flow signals in benign prostatic hyperplasia (BPH). Pulsatile blood flows were detected in all patients, demonstrating a significant increase of the resistive index (RI) in BPH cases (n = 40, 0.72 +/- 0.05, p < 0.0001), compared to those with a healthy prostate (n = 37, 0.64 +/- 0.04). Of 40 patients with BPH, 28 (70%) had an RI of 0.70 or higher; all but 1 patient with a healthy prostate (1 of 37, 3%) had an RI lower than 0.70 (p < 0.0001). In all 10 patients with BPH, the elevated RI decreased significantly to a normal control level after surgical treatment (0.72 +/- 0.02 vs. 0.64 +/- 0.05, p < 0.001). In conclusion, Doppler RI might be useful as a new urodynamic parameter in BPH.

Possible use of ultrasound estimated bladder weight in evaluating vesicoureteral reflux in children.

The present study was designed to reveal the possible use of ultrasound estimated bladder weight (UEBW) in evaluating vesicoureteral reflux (VUR) in children in terms of possible implication of bladder hypertrophy in VUR. In 27 children with VUR, UEBW was measured by transabdominal ultrasound. The UEBW in an individual patient was evaluated quantitatively using the percent deviation from age matched UEBW. There was a significant difference noted in the percent deviation from age-matched UEBW between patients (n = 17) with primary VUR and those (n = 10) with secondary VUR (p <.05). When analyzed together in 27 patients, a significant positive correlation (p <.05) was recognized between the percent deviation from age-matched UEBW and VUR grade. This was also the case in ten patients with secondary VUR (p <.01), but not for 17 patients with primary VUR. The measurement of UEBW might be of clinical use in evaluating the pathogenesis as well as the severity of VUR in children.

[A clinical evaluation on postprostatectomy incontinence].

Postprostatectomy incontinence was evaluated in 193 patients, who underwent retropubic prostatectomy (RPP) or transurethral resection of the prostate (TURP) during the past 5 years from 1985 to 1989 at the Kyoto Prefectural University of Medicine. The occurrence rate of postprostatectomy incontinence was 17.2% in the patients who had undergone RPP and 33.3% of those who had undergone TURP. Although postprostatectomy incontinence disappeared within one week in half of the patients, postprostatectomy incontinence remained for more than one month in 4.9% of the patients who had undergone RPP and 3.3% of those who had undergone TURP. The incidence of postprostatectomy incontinence tended to be high in the patients of advanced ages. Postprostatectomy incontinence recognized in this series was classified into stress incontinence and urgency incontinence groups. An analysis of the results of cystometry performed before the operation showed that the volume of maximum desire of voiding in the urgency incontinence group was smaller than that in the group without postprostatectomy incontinence. Furthermore, supposing the urgency degree as a new parameter, which is defined as a ratio of first desire of voiding to maximum desire of voiding, the urgency degree of the urgency incontinence group was higher than that of the group without postprostatectomy incontinence. Patients with an urgency degree higher than 70% were found to have a high probability of urgency incontinence. These findings suggested that advanced age was the risk factor of postprostatectomy incontinence and that a small bladder capacity and high urgency degree were the high risk factors of postprostatectomy urgency incontinence.

[Ultrasound in urodynamics].

Recent developments of ultrasound imaging have contributed much to the understanding of urodynamics in patients with lower urinary tract symptoms (LUTS). These include ultrasound estimated bladder weight (UEBW), transrectal power Doppler imaging of the prostate and transrectal ultrasonography during voiding (voiding TRUS). UEBW, which is obtained by measuring the thickness of the anterior bladder wall using a 7.5 MHz probe, represents well the degree of bladder hypertrophy caused by obstruction. This parameter is, accordingly, of clinical use in the evaluation of obstruction. The UEBW predicted the presence of obstruction as determined by pressure-flow study with a diagnostic accuracy of 73%. Transrectal power Doppler imaging of the prostate has made it easy to detect prostatic vessels and furthermore to obtain their resistive index (RI). Accumulating data suggest strongly that RI reflects the intraprostatic pressure. More interestingly, RI decreases significantly during voiding in normal subjects but not in patients with benign prostatic hyperplasia. Thus, this method is of particular use in monitoring noninvasively the dynamic change in intraprostatic pressure during voiding. Voiding TRUS makes it possible to monitor the movement of not only the posterior urethra but also the prostate during voiding. Based on our recent study, the anterior fibromuscular stroma (AFMS) seems to contract to open the urethra. Although the physiological function of the AFMS in the prostate remains unknown, AFMS may play a significant role in normal micturition. Due to its noninvasiveness and ease of application, ultrasound imaging would play a vital role in the diagnostic process for patients with LUTS in future.