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.

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.

[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.

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.

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.

Follow-up study of bedwetting from 3 to 5 years of age.

OBJECTIVES: To evaluate the relationship between bedwetting and development in infancy. METHODS: Questionnaires concerning micturition habits and development at 3 and 5 years of age were completed by the parents of 157 children who had had their health checked by pediatricians at a group checkup at 3 years of age. RESULTS: The percentage of bedwetters in whom the frequency of bedwetting was at least once a month was 53% at 3 years of age and 21% at 5 years of age. The prevalent resolution period of bedwetting in infants was 2.5 to 3.5 years of age. The head circumference for boys at birth differed significantly between the bedwetters and nonbedwetters at both ages. Daytime symptoms were more frequent among bedwetters at both ages. Earlier toilet training had no influence on bedwetting at 5 years of age, although it led to earlier control at night at a younger age. Delays in speaking and walking might be factors connected to bedwetting. The prevalence of bedwetting in boys was higher than that in girls. Multiple logistic regression analysis revealed that daytime incontinence and sex were significant factors for bedwetting at 5 years of age. CONCLUSIONS: Daytime incontinence and sex were the significant factors for bedwetting in infancy. Head circumference for boys and developmental delays in speaking and walking might also be important factors.

Possible use of transrectal power Doppler imaging as an indicator of microvascular density of prostate cancer.

OBJECTIVES: To reveal the possible use of transrectal power Doppler imaging (PDI) of the prostate in the assessment of the microvascular density (MVD) of cancer lesions. METHODS: In 22 patients with clinically organ-confined prostate cancer, PDI was performed before radical prostatectomy and the degree of vascularity of the cancer lesions as evaluated by PDI was compared with the MVD determined on the surgical specimens. The vascularity by PDI of each cancer lesion was graded on a scale of DS0 to DS2, according to the degree of Doppler signal accumulation. MVD was obtained using factor VIII immunohistochemistry. RESULTS: The vascularity of the PDI of 46 cancer lesions categorized 23 (50%), 10 (22%), and 13 (28%) cancer lesions as DS0, DS1, and DS2, respectively. Significant differences were found in the MVD between DS0 (46.6 +/- 26.8) and DS2 (89.0 +/- 18.1, P <0.005) lesions and between DS1 (50.9 +/- 25.4) and DS2 (P <0.001) lesions. The MVD of 30 cancer lesions in 13 patients without neoadjuvant therapy was significantly higher than that of the 16 lesions in 9 patients with therapy (70.2 +/- 28.2 versus 39.5 +/- 23.9, P <0.001). In the 13 patients without neoadjuvant therapy, the MVD of the DS2 lesions (89.1 +/- 18.9) was significantly higher than that of the DS0 lesions (59.3 +/- 32.5, P <0.01) and DS1 lesions (55.9 +/- 20.9, P <0.005). CONCLUSIONS: The semiquantitative assessment of Doppler flow signals using PDI appears to be of clinical value as an indicator of MVD.

Alternative splicing isoforms of hippostasin (PRSS20/KLK11) in prostate cancer cell lines.

BACKGROUND: Hippostasin is a kallikrein-like protease (PRSS20/KLK11), which is expressed preferentially in the hippocampus and prostate. We have reported that alternative splicing variants of human hippostasin are regulated in a tissue-specific manner. Brain-type hippostasin consists of 250 amino acids including a typical signal sequence, and is expressed in the brain and prostate. The prostate-type hippostasin, which has 32 extra amino acids at the N-terminal end, is expressed only in the prostate. METHODS: We analyzed the expression and localization of hippostasin in normal prostate tissue, BPH tissue, and prostate cancer cell lines. We performed northern blotting, in situ hybridization, immunohistochemistry, and RT-PCR. RESULTS: Hippostasin mRNA is expressed preferentially in the normal prostate and weakly in the testis. It was detected in prostate secretory epithelium. Hippostasin protein was localized in the prostate secretory epithelium, and western blotting showed that hippostasin was present in semen. All tested prostate cancer cell lines, including PSA-negative cell lines, expressed hippostasin. Interestingly, all the prostate cancer cell lines expressed only brain-type but not prostate-type hippostasin, while normal prostate and BPH expressed both types of hippostasin CONCLUSIONS: Our results suggest the possibility that hippostasin may be a useful marker by which prostate cancer and BPH can be distinguished.

Immunohistochemical studies on the distribution of nerve fibers in the human prostate with special reference to the anterior fibromuscular stroma.

BACKGROUND: Although the anterior fibromuscular stroma (AFMS) comprises up to one third of the total bulk of the prostate, its physiological function remains unknown. We recently reported the possible contribution of the AFMS to micturition. The aim of this study is to reveal the differences in the distribution of innervation between the AFMS and the other regions of the prostate. METHODS: We performed immunohistochemical stainings using antibodies such as protein gene product (PGP) 9.5, tyrosine hydroxylase(TH), neuropeptide Y (NPY), and vasoactive intestinal peptide (VIP). Morphometric analysis was made to examine the density of peripheral nerve fibers containing PGP 9.5, TH, NPY, and VIP by using a computer-assisted imaging system. RESULTS: The number of PGP 9.5-immunoreactive (IR) nerve fibers and the smooth muscle in the AFMS decreased from the base to the apex of the prostate. TH-IR nerve fibers were more abundant in the AFMS than in the transition zone. NPY- and VIP-IR nerve fibers were less numerous in the AFMS than in the peripheral zone. CONCLUSIONS: This study is the first to demonstrate that the AFMS has peculiar neuronal innervation. We observed significantly different innervation in the AFMS compared with the other regions of the prostate.

Evaluation of reflux kidney using renal resistive index.

PURPOSE: We clarified the relationships of the renal resistive index, reflux and renal scarring. MATERIALS AND METHODS: The resistive index in the interlobar artery was measured using power Doppler ultrasonography in 22 patients with reflux (reflux group), 13 with postoperative or resolved reflux (previous reflux group) and 20 who served as controls. RESULTS: Resistive index values in 11 kidneys with mid or high grade reflux were significantly higher than in 22 with low grade reflux and in the 40 normal kidneys. The resistive index in the 11 kidneys with reflux and scarring was significantly higher than in the 22 with reflux and without scarring, and in the 40 normal kidneys. The resistive index in the 14 kidneys with previous reflux and scarring was significantly higher than in 12 with previous reflux and without scarring, and in the 40 normal kidneys. Receiver operating characteristics curve analysis in 25 kidneys with and 34 without scarring revealed that a discriminatory resistive index value of 0.71 was optimal for detecting renal scarring. When the resistive index cutoff value was 0.71, there was 76% sensitivity for diagnosing renal scarring, 91% specificity and 85% overall accuracy. CONCLUSIONS: Our results show the possibility that an increased resistive index in kidneys with reflux predicts renal scarring. The resistive index measured with power Doppler ultrasonography may be a noninvasive and useful alternative for screening and following renal scarring.

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.

Immunohistochemical localization of platelet-derived endothelial cell growth factor expression and its relation to angiogenesis in prostate.

OBJECTIVES: Tumor angiogenesis has been reported as a predictor for prognosis in patients with prostate cancer. The aim of this study was to determine the localization of one angiogenic factor, platelet-derived endothelial cell growth factor (PD-ECGF), in benign and malignant prostatic tissues and the correlation between PD-ECGF expression and microvessel density (MVD) in prostate cancer. METHODS: Forty cases of prostate cancer, 3 cases of benign prostatic hyperplasia, and 5 young autopsy cases without prostatic disease were processed with immunohistochemistry, using an anti-PD-ECGF antibody and anti-factor VIII-related antigen antibody. The PD-ECGF expression intensity and MVD were evaluated in each case. RESULTS: In the 40 cases with prostate cancer, the expression of PD-ECGF was noted in the stromal cells within cancer tissues in 80% of cases. Additionally, noncancerous glands next to cancer lesions were positive for PD-ECGF in 85% of cases. However, cancer cells were negative for PD-ECGF in all cases. In the 8 cases without cancer, both the prostatic glands and their surrounding stroma were positive for PD-ECGF only when they were accompanied by inflammation. There was a significant positive correlation (r = 0.636, P <0.001) between the intensity of PD-ECGF expression and MVD. MVD was significantly different when comparing the intensity of PD-ECGF expression of grade 0 versus grade 1 (P <0.05), grade 1 versus grade 2 (P <0.05), and grade 0 versus grade 2 (P <0.01). CONCLUSIONS: This study suggested that PD-ECGF expression in the stromal cells within cancer tissues might play an important role in tumor angiogenesis in prostate cancer.

Acupuncture on clinical symptoms and urodynamic measurements in spinal-cord-injured patients with detrusor hyperreflexia.

OBJECTIVES: We investigated the possible use of acupuncture for the treatment of urinary incontinence caused by detrusor hyperreflexia in patients with chronic spinal cord injuries. METHODS: A total of 13 patients (11 males, 2 females) suffering from urinary incontinence due to spinal cord injuries were treated by acupuncture, which was carried out with disposable stainless steel needles inserted into the bilateral BL-33 (Zhongliao) points on the skin of the third posterior sacral foramina. Urodynamic studies were also performed before acupuncture, immediately after the 1st acupuncture and 1 week after the 4th acupuncture. In 6 patients, these urodynamic studies were performed again 1 month after the 4th acupuncture. RESULTS: No side effects were recognized throughout the treatment period. Of the 13 patients, incontinence disappeared in 2 (15%) and decreased to 50% or less compared to baseline in a further 6 (46%). Maximum cystometric bladder capacity increased significantly from 76.2 +/- 62.3 to 148.1 +/- 81.5 ml 1 week after the 4th acupuncture (p < 0.01). In the 6 patients in whom cystometry was repeated 1 month after the 4th acupuncture, bladder capacity decreased from 187.5 +/- 90.4 ml 1 week after the 4th acupuncture to 128.3 +/- 93.4 ml. CONCLUSION: In spinal cord injury patients acupuncture could represent another valuable therapeutic alternative to the treatment of urinary incontinence caused by detrusor hyperreflexia.