Hyperthermia treatment planning including convective flow in cerebrospinal fluid for brain tumour hyperthermia treatment using a novel dedicated paediatric brain applicator

Hyperthermia therapy (40–44 \ub0C) is a promising option to increase efficacy of radiotherapy/chemotherapy for brain tumours, in particular paediatric brain tumours. The Chalmers Hyperthermia Helmet is developed for this purpose. Hyperthermia treatment planning is required for treatment optimisation, but current planning systems do not involve a physically correct model of cerebrospinal fluid (CSF). This study investigates the necessity of fluid modelling for treatment planning. We made treatments plans using the Helmet for both pre-operative and post-operative cases, comparing temperature distributions predicted with three CSF models: A convective “fluid” model, a non-convective “solid” CSF model, and CSF models with increased effective thermal conductivity (“high-k”). Treatment plans were evaluated by T90, T50 and T10 target temperatures and treatment-limiting hot spots. Adequate heating is possible with the helmet. In the pre-operative case, treatment plan quality was comparable for all three models. In the post-operative case, the high-k models were more accurate than the solid model. Predictions to within \ub11 \ub0C were obtained by a 10–20-fold increased effective thermal conductivity. Accurate modelling of the temperature in CSF requires fluid dynamics, but modelling CSF as a solid with enhanced effective thermal conductivity might be a practical alternative for a convective fluid model for many applications

Impact on genitourinary function and quality of life following focal irreversible electroporation of different prostate segments

© Turkish Society of Radiology 2018. PURPOSE We aimed to evaluate the genitourinary function and quality of life (QoL) following the ablation of different prostate segments with irreversible electroporation (IRE) for localized prostate cancer (PCa). METHODS Sixty patients who received primary focal IRE for organ-confined PCa were recruited for this study. Patients were evaluated for genitourinary function and QoL per prostate segment treated (anterior vs. posterior, apex vs. base vs. apex-to-base, unilateral vs. bilateral). IRE system settings and patient characteristics were compared between patients with preserved vs. those with impaired erectile function and urinary continence. Data were prospectively collected at baseline, 3, 6, and 12 months using the expanded prostate cancer index composite, American Urological Association symptom score, SF-12 physical and mental component summary surveys. Difference over time within segments per questionnaire was evaluated using the Wilcoxon’s signed rank test. Outcome differences between segments were assessed using covariance models. Baseline measurements included questionnaire scores, age, and prostate volume. RESULTS There were no statistically significant changes over time for overall urinary (P = 0.07-0.89), bowel (P = 0.06-0.79), physical (P = 0.18-0.71) and mental (P = 0.45-0.94) QoL scores within each segment. Deterioration of sexual function scores was observed at 6 months within each segment (P = 0.001-0.16). There were no statistically significant differences in QoL scores between prostate segments (P = 0.08-0.97). Older patients or those with poor baseline sexual function at time of treatment were associated with a greater risk of developing erectile dysfunction. CONCLUSION IRE is a feasible modality for all prostate segments without any significantly different effect on the QoL outcomes. Older patients and those with poor sexual function need to be counseled regarding the risk of erectile dysfunction

Profiling the proteoforms of urinary prostate-specific antigen by capillary electrophoresis-mass spectrometry

Early detection of prostate cancer may lead to the overdiagnosis and overtreatment of patients as well as missing significant cancers. The current diagnostic approach uses elevated serum concentrations of prostate-specific antigen (PSA) as an indicator of risk. However, this test has been widely criticized as it shows poor specificity and sensitivity. In order to improve early detection and diagnosis, several studies have investigated whether different PSA proteoforms are correlated to prostate cancer. Until now, studies and methodologies for the comprehensive characterization of PSA proteoforms from biofluids are scarce. For this purpose, we developed an intact protein assay to analyze PSA by capillary electrophoresis-electrospray ionization-mass spectrometry after affinity purification from patients? urine. Here, we determined six proteolytic cleavage variants. In regard to glycosylation, tri-, di-, mono- and non-sialylated complex-type N-glycans were found on non-cleaved PSA, as well as the non-glycosylated variant. The performance of the intact protein assay was assessed using a pooled sample, obtaining an inter-day variability of 15%. Furthermore, urinary patient samples were analyzed by intact protein analysis and a bottom-up approach (glycopeptide analysis). This combined approach revealed complimentary information on both levels, demonstrating the benefit of using two orthogonal techniques to provide a thorough profile of urinary PSA.Significance: The detection of clinically relevant prostate cancer requires a more specific and sensitive biomarker and, in this case, several PSA proteoforms may be able to aid or improve the current PSA test. However, a comprehensive analysis of the intact PSA proteoform profile is still lacking. This study investigated the PSA proteoforms present in urine and, in particular, determined the relative contribution of cleaved PSA and noncleaved PSA forms to the total glycosylation profile. Importantly, intact protein analysis did not require further sample treatment before being measured by CE-ESI-MS. Furthermore, its glycosylation was also assessed in a bottom-up approach to provide complementary information. Overall, these results represent an important basis for future characterization and biomarker studies.Proteomic

Role of marker lesion when applying intravesical instillations of IL-2 for non-muscle-invasive bladder cancer comparison of the therapeutic effects in two pilot studies

Comparison of the therapeutic effect of treatment of non-muscle invasive bladder carcinoma (NMIBC) after intravesical Interleukin-2 (IL-2) instillations in the presence and absence of a marker tumour. Two pilot studies were performed in patients with NMIBC. The first study (10 patients) was performed in Krakow (Poland), the second (26 patients) in Vilnius (Lithuania). In Krakow the tumours were treated with incomplete transurethral resection (TUR) leaving a marker tumour of 0.5-1.0-cm followed by IL-2 instillations (3 × 10(6) IU IL-2) on five consecutive days. In Vilnius the tumours were treated with complete TUR, followed by IL-2 instillations (9 × 10(6) IU IL-2) on five consecutive days. During 30 months follow-up, the recurrence-free survival was 5/10 (50%) and 6/26 (23%) after incomplete and complete TUR, respectively. So, the ratio of the recurrence-free survival after incomplete/complete TUR of 50/23=2.2. The median of the recurrence-free survival is >20.5 months and 7 months after incomplete and complete TUR, respectively. So, this ratio was >20.5/7= >2.9. The hazard ratio which combines both the chance of the disease recurrence and its timing for both censored and uncensored cases was 0.53, again confirming the better outcome after incomplete TUR. A possible explanation for the better therapeutic effects after incomplete TUR compared with complete TUR is that the marker tumour has tumour-associated antigens (TAA) that could lead to an immune reaction that is stimulated by local application of IL-2. After complete TUR, no TAA are available to initiate and to stimulate an immune reaction; consequently, local IL-2 therapy is less effective after complete TUR. The results of these two pilot studies have led to the recent start of a randomised prospective clinical trial in which therapeutic effects of local IL-2 therapy after complete and incomplete TUR are compare

Novel minimally invasive treatments for lower urinary tract symptoms: a systematic review and network meta-analysis

ABSTRACT Purpose: To review and compare the effectivity of novel minimally invasive treatments (MITs) to transurethral resection of the prostate (TURP) for the treatment of lower urinary tract symptoms (LUTS) in men. Methods: Medline, Embase, and Cochrane databases were searched from January 2010 to December 2022 for randomized controlled trials (RCTs) evaluating MITs, compared to TURP or sham, in men with LUTS. Studies were assessed by risk of bias tool, and evidence by GRADE. Functional outcomes by means of uroflowmetry and IPSS were the primary outcomes, safety and sexual function were secondary outcomes. As part of this review, a network meta-analysis (NMA) was conducted. MITs were ranked based on functional outcome improvement probability. Results: In total, 10 RCTs were included, evaluating aquablation, prostatic urethral lift, prostatic artery embolization (PAE), convective water vapor thermal treatment or temporary implantable nitinol device. All MITs showed a better safety profile compared to TURP. Functional outcome improvement following aquablation were comparable to TURP. In the NMA, aquablation was ranked highest, PAE followed with the second highest probability to improve functional outcomes. Other novel MITs resulted in worse functional outcomes compared to TURP. Level of evidence was low to very low. Conclusions: Five MITs for treatment of LUTS were identified. Aquablation is likely to result in functional outcomes most comparable to TURP. Second in ranking was PAE, a technique that does not require general or spinal anesthesia. MITs have a better safety profile compared to TURP. However, due to high study heterogeneity, results should be interpreted with caution

Guideline on urothelial carcinoma of the bladder

Urothelial carcinoma of the bladder is diagnosed predominantly in people over 60 years of age. The most common symptom is haematuria. Smoking is an important risk factor (relative risk 2.5 to 3). Cystoscopy is performed whenever bladder carcinoma is suspected. The recurrence rate of a non-muscle invasive urothelial carcinoma is high (31-78% within 5 years). A single intravesical instillation with a chemotherapeutic agent within 24 hours of transurethral resection (TUR) reduces the risk of recurrence. Carcinoma in situ (CIS) should be treated as high-grade urothelial carcinoma. Standard treatment for patients with non-metastasized muscle-invasive urothelial carcinoma is cystectomy in combination with extensive lymph node dissection. There are several possibilities for urinary diversion following cystectomy, none of which are any better than the others. Bladder-sparing brachytherapy may be used in patients with solitary T1 - T2 urothelial carcinoma &lt; 5 cm. Neoadjuvant cisplatin-containing chemotherapy prior to cystectomy in muscle-invasive carcinoma only slightly improves survival. Cisplatin-containing combination chemotherapy is the standard treatment for metastasized urothelial carcinoma.</p