Survey of imaging dose in HDR brachytherapy

Institutional imaging protocols for the verification of brachytherapy applicator placements were investigated in a survey study of domestic radiotherapy institutions. The survey form designed by a free on-line survey system was distributed via the mailing-list system of the Japanese Society for Radiation Oncology. Survey data of 75 institutions between August 2019 and October 2019 were collected. The imaging modalities used were dependent on resources available to the institutions. The displacement of a brachytherapy applicator results in significant dosimetric impact. It is essential to verify applicator placements using imaging modalities before treatment. Various imaging modalities used in institutions included a computed tomography (CT) scanner, an angiography X-ray system, a multi-purpose X-ray system and a radiotherapy simulator. The median total exposure time in overall treatment sessions was ≤75 s for gynecological and prostate cancers. Some institutions used fluoroscopy to monitor the brachytherapy source movement. Institutional countermeasures for reducing unwanted imaging dose included minimizing the image area, changing the imaging orientation, reducing the imaging frequency and optimizing the imaging conditions. It is worth noting that half of the institutions did not confirm imaging dose regularly. This study reported on the usage of imaging modalities for brachytherapy in Japan. More caution should be applied with interstitial brachytherapy with many catheters that can lead to potentially substantial increments in imaging doses for monitoring the actual brachytherapy source using fluoroscopy. It is necessary to share imaging techniques, standardize imaging protocols and quality assurance/quality control among institutions, and imaging dose guidelines for optimization of imaging doses delivered in radiotherapy should be developed

Clinical Utility of Germline Genetic Testing in Japanese Men Undergoing Prostate Biopsy

Background: Multiple common variants and also rare variants in monogenic risk genes such as BRCA2 and HOXB13 have been reported to be associated with risk of prostate cancer (PCa); however, the clinical setting in which germline genetic testing could be used for PCa diagnosis remains obscure. Herein, we tested the clinical utility of a 16 common variant-based polygenic risk score (PRS) that has been developed previously for Japanese men and also evaluated the frequency of PCa-associated rare variants in a prospective cohort of Japanese men undergoing prostate biopsy. Methods: A total of 1336 patients undergoing first prostate biopsy were included. PRS was calculated based on the genotype of 16 common variants, and sequencing of 8 prostate cancer-associated genes was performed by multiplex polymerase chain reaction based target sequencing. PRS was combined with clinical factors in logistic regression models to assess whether addition of PRS improves the prediction of biopsy positivity. Results: The top PRS decile was associated with an odds ratio of 4.10 (95% confidence interval = 2.46 to 6.86) with reference to the patients at average risk, and the estimated lifetime absolute risk approached 20%. Among the patients with prostate specific antigen 2-10 ng/mL who had prebiopsy magnetic resonance imaging, high PRS had an equivalent impact on biopsy positivity as a positive magnetic resonance imaging finding. Rare variants were detected in 19 (2.37%) and 7 (1.31%) patients with positive and negative biopsies, respectively, with BRCA2 variants being the most prevalent. There was no association between PRS and high-risk rare variants. Conclusions: Germline genetic testing could be clinically useful in both pre- and post-PSA screening settings

The effect of ovariectomy on urethral continence mechanisms during sneeze reflex in middle-aged versus young adult rats

Aims: Stress urinary incontinence (SUI) is common in post-menopausal women. The present study therefore examined how aging and estrogen deficiency induced by ovariectomy (OVX) affect the urethral continence mechanism that prevents sneeze-induced SUI in rats. Methods: Young (3 months old) and middle-aged (12 months old) female rats underwent bilateral OVX or sham operation. Urethral activity was measured by the amplitude of urethral responses during sneezing (A-URS) and urethral baseline pressure (UBP). Apoptotic changes in urethral tissue sections were examined by the TUNEL method. Results: In middle-aged rats, UBP, but not A-URS, was significantly decreased compared to young rats. In 3-week OVX rats, A-URS was significantly decreased compared to sham rats in both young and middle-aged groups, and the OVX-induced reduction in A-URS was more pronounced in middle-aged rats. Neither young 3-week OVX nor sham rats leaked during sneezing; however, SUI occurred in 2/8 middle-aged rats with 3-week OVX, and after 6 weeks of OVX, SUI was observed in 5/8 young rats and 6/8 middle-aged rats. In middle-aged rats, TUNEL positive cells were significantly increased in urethral striated muscles whereas, after OVX, the increased number of positive cells was also found in the mucosa. Conclusions: These results indicate that aging is more likely to impair baseline urethral function than striated muscle-mediated reflex activity although apoptotic changes are found in urethral striated muscle. Estrogen deficiency additionally impairs the striated muscle-mediated continence reflex. Thus, aging and estrogen deficiency differently and additively affect baseline urethral function and neurally-evoked, striated muscle-mediated urethral continence mechanisms to induce SUI

Phosphodiesterase type 5 inhibitor administered immediately after radical prostatectomy temporarily increases the need for incontinence pads, but improves final continence status

Purpose: To evaluate the effects of phosphodiesterase type 5 inhibitor (PDE5i) on urinary continence recovery after bilateral nerve-sparing radical prostatectomy (BNSRP). Materials and Methods: Between 2002 and 2012, 137 of 154 consecutive patients who underwent BNSRP in our institution retrospectively divided into 3 groups that included patients taking PDE5i immediately after surgery (immediate PDE5i group, n=41), patients starting PDE5i at an outpatient clinic after discharge (PDE5i group, n=56), and patients taking no medication (non-PDE5i group, n=40). Using self-administered questionnaires, the proportion of patients who did not require incontinence pads (pad-free patients) was calculated preoperatively and at 1, 3, 6, 12, 18, and 24 months after BNSRP. Severity of incontinence was determined based on the pad numbers and then compared among the 3 groups. Results: Proportions of pad-free patients and severity of incontinence initially deteriorated in all of the groups to the lowest values soon after undergoing BNSRP, with gradual improvement noted thereafter. The deterioration was most prominent in the immediate PDE5i group. As compared to the non-PDE5i group, both the PDE5i and immediate PDE5i groups exhibited a better final continence status. Conclusions: PDE5i improves final continence status. However, administration of PDE5i immediately after surgery causes a distinct temporary deterioration in urinary incontinence

Low-energy shock wave therapy ameliorates ischemic-induced overactive bladder in a rat model

Abstract This study was to evaluate whether Low-energy shock wave therapy (LESW) improves ischemic-induced overactive bladder in rats and investigate its therapeutic mechanisms. Sixteen-week-old male Sprague–Dawley rats were divided into three groups: arterial injury (AI), AI with LESW (AI-SW), and control groups. LESW was irradiated in AI-SW during 20–23 weeks of age. At 24 weeks of age, conscious cystometry was performed (each n = 8). The voiding interval was shortened in AI (mean ± SEM: 5.1 ± 0.8 min) than in control (17.3 ± 3.0 min), whereas significant improvements were observed in AI-SW (14.9 ± 3.3 min). The bladder blood flow was significantly increased in AI-SW than in AI. Microarray analysis revealed higher gene expression of soluble guanylate cyclase (sGC) α1 and β1 in the bladder of AI-SW compared to AI. Protein expression of sGCα1 and sGCβ1 was higher in AI-SW and control groups than in AI. Cyclic guanosine monophosphate (cGMP) was elevated in AI-SW. As an early genetic response, vascular endothelial growth factor and CD31 were highly expressed 24 h after the first LESW. Suburothelial thinning observed in AI was restored in AI-SW. Activation of sGC-cGMP may play a therapeutic role of LESW in the functional recovery of the bladder