Physician reported toxicities and patient reported quality of life of transperineal ultrasound-guided radiotherapy of prostate cancer.

Purpose: This study aims to address therapy-related toxicities and quality of life in prostate cancer patients undergoing transperineal ultrasound (TPUS) guided radiotherapy (RT). Methods: Acute and late gastrointestinal (GI) and genitourinary (GU) toxicities were assessed by physicians using CTCAE v5.0. Patient-reported quality of life outcomes were evaluated using EORTC QLQ-C30, -PR25 and IPSS. We utilized Volumetric Modulated Arc Therapy (VMAT) or intensity modulated radiation therapy (IMRT) as the RT technique for this study. The assessments were carried out before RT, at RT end, 3 months after RT and subsequently at 1-year intervals. Prostate-specific antigen (PSA) was also evaluated at each follow-up. Results: In this study, a total of 164 patients were enrolled, while among them, 112 patients delivered quality-of-life data in a prospective evaluation. The median pre-treatment PSA was 7.9 ng/mL (range: 1.8-169 ng/ml). At the median follow-up of 19 months (3-82 months), the median PSA decreased to 0.22 ng/ml. Acute grade II GI and GU toxicities occurred in 8.6 % and 21.5 % patients at RT end. Regarding late toxicities, 2.2 % patients experienced grade II GI toxicities at 27 months and only one patient at 51 months, whereas no grade II GU late toxicities were reported at these time points. Quality of life scores also indicated a well-tolerated treatment. Patients mainly experienced acute clinically relevant symptoms of fatigue, pain, as well as deterioration in bowel and urinary symptoms. However, most symptoms normalized at 3 months and remained stable thereafter. Overall functioning showed a similar decline at RT end but improved over time. Conclusion: The outcomes of TPUS-guided RT demonstrated promising results in terms of minimal physician-reported toxicities and satisfactory patient-reported QoL.

Effects of Intraoperative Opioid Use and a Combined Anesthesia Protocol in Patients Undergoing Radical Cystectomy for Urothelial Carcinoma of the Bladder-A Single-Center Experience.

BACKGROUND: An increased intraoperative opioid dose seems to lead to worse outcomes in several types of cancer. We assessed the effect of intraoperatively administered opioids as well as the type of anesthesia on survival, recurrence rates and major perioperative outcomes in patients who underwent radical cystectomy (RC) for urothelial carcinoma of the urinary bladder. METHODS: We included patients who underwent open RC at our center between 2015 and 2022. The role of the type and dosage of intraoperative opioid agents, such as remifentanil, sufentanil and morphine milligram equivalents (MME), as well as the type of anesthesia (intravenous only versus intravenous/epidural), was assessed regarding perioperative and long-term outcomes after RC. RESULTS: A total of 508 patients with a median age of 73 years (IQR: 64-78) were included. Overall, 92 (18%) patients received intravenous anesthesia, whereas 416 (82%) received combined anesthesia. At a median follow-up of 270 days (IQR: 98-808), 108 (21%) deaths and 106 (21%) recurrences occurred. Combined anesthesia was associated with better survival (HR:0.63, 95% CI: 0.4-0.97, p = 0.037) and lower intensive care unit admission rates (OR: 0.49, 95% CI: 0.31-0.77, p = 0.002) in the univariate analysis (unadjusted). The type and dosage of intraoperative opioid agents did not affect long-term survival and recurrence rates, as well as major perioperative outcomes. Nevertheless, the findings of our study were limited by its single-center, retrospective design. CONCLUSION: The use of intraoperative opioids was not associated with worse outcomes in our cohort, while the use of additional epidural anesthesia seems to be beneficial in terms of overall survival and intensive care unit admissions. Nevertheless, further research is mandatory to validate the safety of opioids in patients undergoing RC.

PSMA-PET/CT response after metastasis-directed radiotherapy of bone oligometastases in prostate cancer.

OBJECTIVE: Bone metastases are very common in advanced prostate cancer and can sensitively be detected utilizing PSMA-PET/CT. Therefore, our goal was to evaluate the suitability of PSMA-PET/CT-guided metastasis-directed external beam radiotherapy (MDT) as treatment option for patients with biochemical recurrence and oligometastatic bone lesions. MATERIALS & METHODS: We retrospectively examined 32 prostate cancer patients with biochemical recurrence and PSMA-positive oligometastatic disease limited to the bone (n = 1-3). A total of 49 bone lesions were treated with MDT. All patients received a post-radiotherapy PSMA-PET/CT-Scan. Changes in SUVmax, PSMA-positive tumor volume per lesion and PSA, as well as the correlation between the PET/CT-interval and SUVmax response were calculated. RESULTS: MDT lead to a SUVmax decrease in 46/49 (94%) of the lesions. The median relative decline of SUVmax was 60.4%, respectively. Based on PSMA-positive lesion volume with a SUV cut-off of 4, 46/49 (94%) of lesions showed complete response, two (4%) partial response and one lesion (2%) was stable on PSMA-PET/CT after MDT. Most of the treated patients (56.3%) showed an initial PSA decline at three months and a PSA nadir of median 0.14 ng/ml after a median time of 3.6 months after MDT. The median relative PSA change at three months after MDT was 3.9%. CONCLUSION: MDT is a very effective treatment modality for prostate cancer bone oligometastases and lesion response to MDT can be assessed using the (semi-)quantitative parameters SUVmax and PSMA-positive lesion volume with established SUV cut-offs.

The impact of preoperative 5-alpha reductase inhibitors on functional outcomes and health-related quality of life following radical prostatectomy - A propensity score matched longitudinal study.

OBJECTIVES: While the impact of treatment with 5-alpha Reductase Inhibitors (5-ARI) on the risk of cancer-related mortality in men with prostate cancer (PC) has been extensively studied, little is known about the impact of preoperative 5-ARI use on patient-reported outcomes (PROs) following radical prostatectomy (RP). METHODS: Within our prospectively maintained institutional database of 5899 patients treated with RP for PC (2008- 2021), 99 patients with preoperative 5-ARI therapy were identified. A 1:4 propensity-score matched analysis of 442 men (n = 90 5-ARI, n = 352 no 5-ARI) was conducted. Primary endpoint was continence recovery using daily pad usage and ICIQ-SF. Health-related quality of life (HRQOL) was assessed using the validated EORTC QLQ-C30 and PR25 questionnaires. Multivariable Cox-regression-models tested the effect of preoperative 5-ARI treatment on continence-recovery (p < 0.05). RESULTS: Patients were followed up perioperatively, followed by annual assessments up to 60mo postoperatively. Preoperative mean ICIQ-SF score (2.2 vs. 0.9) was significantly higher in the 5-ARI cohort (p = 0.006). 24mo postoperatively, 68.6% (no 5-ARI) vs. 55.7% (5-ARI) had full continence recovery (p = 0.002). Multivariable Cox regression analysis, revealed preoperative 5-ARI treatment as an independent predictor for impaired continence recovery (HR 0.50, 95% CI 0.27-0.94, p = 0.03) In line, general HRQOL was significantly higher for patients without 5-ARI only up to 24mo postoperatively (70.6 vs. 61.2, p = 0.045). There was no significant impact of preoperative 5-ARI treatment on erectile function, biochemical recurrence-free survival and metastasis-free survival. CONCLUSIONS: Pre-RP 5-ARI treatment was associated with impaired continence outcomes starting 24mo postoperatively, suggesting that preoperative 5-ARI treatment can impair the long-term urinary function recovery following RP.

Investigation on the influence of the skin tone on hyperspectral imaging for free flap surgery.

Hyperspectral imaging (HSI) is a new emerging modality useful for the noncontact assessment of free flap perfusion. This measurement technique relies on the optical properties within the tissue. Since the optical properties of hemoglobin (Hb) and melanin overlap, the results of the perfusion assessment and other tissue-specific parameters are likely to be distorted by the melanin, especially at higher melanin concentrations. Many spectroscopic devices have been shown to struggle with a melanin related bias, which results in a clinical need to improve non-invasive perfusion assessment, especially for a more pigmented population. This study investigated the influence of skin tones on tissue indices measurements using HSI. In addition, other factors that might affect HSI, such as age, body mass index (BMI), sex or smoking habits, were also considered. Therefore, a prospective feasibility study was conducted, including 101 volunteers from whom tissue indices measurements were performed on 16 different body sites. Skin tone classification was performed using the Fitzpatrick skin type classification questionnaire, and the individual typology angle (ITA) acquired from the RGB images was calculated simultaneously with the measurements. Tissue indices provided by the used HSI-device were correlated to the possible influencing factors. The results show that a dark skin tone and, therefore, higher levels of pigmentation influence the HSI-derived tissue indices. In addition, possible physiological factors influencing the HSI-measurements were found. In conclusion, the HSI-based tissue indices can be used for perfusion assessment for people with lighter skin tone levels but show limitations in people with darker skin tones. Furthermore, it could be used for a more individual perfusion assessment if different physiological influencing factors are respected.

Impact of Preoperative LUTS on Health-related Quality of Life Following Radical Prostatectomy: A Propensity Score Matched Longitudinal Study.

OBJECTIVE: To assess the impact of preoperative lower urinary tract symptoms (LUTS) on long-term health-related quality of life (HRQOL) up to 10 years after radical prostatectomy (RP) for prostate cancer (PC). METHODS: Within our prospective institutional database of 6487 patients treated with RP for PC (2008-2020), 2727 patients with preoperative LUTS (IPSS score of ≥8) were identified. A 1:1 propensity-score matched analysis of 3056 men (n = 1528 LUTS, n = 1528 no LUTS) was conducted. Primary endpoint was HRQOL (based on EORTC QLQ-C30 and PR25). Linear regression models tested the effect of preoperative LUTS on the net change in general HRQOL (P <.05). RESULTS: Median follow-up was 48 months. Preoperative mean global health status (GHS) score (67.4 vs 75.7) was significantly lower in the LUTS cohort (P <.001). Post-RP the difference in general HRQOL between the LUTS cohort and the no-LUTS cohort became smaller (65.7 vs 67.8), however, remaining statistically significant (P = .037). In long-term follow-up, general HRQOL was comparable between both subcohorts (P-range 0.716-0.876). Multivariable linear regression analysis revealed increased preoperative IPSS as an independent predictor for increased perioperative improvement of IPSS (P <.001) CONCLUSION: For patients undergoing RP, preoperative LUTS were associated with a postoperative improvement of HRQOL outcomes. In long-term follow-up, HRQOL was comparable to patients without preoperative LUTS. Hence, RP is an efficient option to treat PC as well as LUTS in those patients.

Influence of vitamins and food on the fluorescence spectrum of human urine.

OBJECTIVES: Fluorescence spectroscopy of human urine is a method with the potential to gain importance as a diagnostic tool in the medical field, e.g., for measuring Coproporphyrin III (CPIII) as an indicator of cancer and acute types of porphyria. Food can change human urine's color, which could influence the urine fluorescence spectrum and the detection of CPIII in urine. To determine if there is a noticeable influence on the urine fluorescence spectrum or on the detection of CPIII in urine, 16 vitamin supplements, and three food items were tested. Such investigation may also prevent false interpretation of measured data. METHODS: Urine samples were collected before and after (overnight, ca. 8 h) intake of each test substance. Samples were investigated by fluorescence spectrum analysis. At excitation wavelengths from 300 to 500 nm and emission wavelengths from 400 to 700 nm excitation-emission-matrices were measured. Data obtained from urine before intake were compared to the data from overnight urine. Furthermore, the investigation of any interference with the CPIII concentration was performed at an excitation wavelength of 407 ± 3 nm and emission wavelengths of 490-800 nm. RESULTS: Only vitamin B2, but none of the other tested substances, showed noticeable influence on the urine fluorescence spectrum. None of the tested substances showed noticeable interference with the recovery rate of CPIII. CONCLUSIONS: The correct interpretation of measured data by fluorescence spectroscopy is possible with the exception if vitamin B2 supplementation was performed; thus, the consumption of vitamin B2 supplements before fluorescence testing of the patient's urine should be avoided and/or must be requested. CPIII concentrations could reliably be measured in all cases.

The effect of hospital caseload on perioperative mortality, morbidity and costs in bladder cancer patients undergoing radical cystectomy: results of the German nationwide inpatient data.

OBJECTIVES: To determine a data-based optimal annual radical cystectomy (RC) hospital volume threshold and evaluate its clinical significance regarding perioperative mortality, complications, length of hospital stay, and hospital revenues. MATERIAL AND METHODS: We used the German Nationwide inpatient Data, provided by the Research Data Center of the Federal Bureau of Statistics (2005-2020). 95,841 patients undergoing RC were included. Based on ROC analyses, the optimal RC threshold to reduce mortality, ileus, sepsis, transfusion, hospital stay, and costs is 54, 50, 44, 44, 71 and 76 cases/year, respectively. Therefore, we defined an optimal annual hospital threshold of 50 RCs/year, and we also used the threshold of 20 RCs/year proposed by the EAU guidelines to perform multiple patient-level analyses. RESULTS: 28,291 (29.5%) patients were operated in low- (< 20 RC/year), 49,616 (51.8%) in intermediate- (20-49 RC/year), and 17,934 (18.7%) in high-volume (≥ 50 RC/year) centers. After adjusting for major risk factors, high-volume centers were associated with lower inpatient mortality (OR 0.72, 95% CI 0.64-0.8, p < 0.001), shorter length of hospital stay (2.7 days, 95% CI 2.4-2.9, p < 0.001) and lower costs (457 Euros, 95% CI 207-707, p < 0.001) compared to low-volume centers. Patients operated in low-volume centers developed more perioperative complications such as transfusion, sepsis, and ileus. CONCLUSIONS: Centralization of RC not only improves inpatient morbidity and mortality but also reduces hospital stay and costs. We propose a threshold of 50 RCs/year for optimal outcomes.

Oncological impact of perioperative blood transfusion in bladder cancer patients undergoing radical cystectomy: Do we need to consider storage time of blood units, donor age, or gender matching?

BACKGROUND: The oncological impact of perioperative blood transfusions (PBTs) of patients undergoing radical cystectomy (RC) because of bladder cancer (BCa) has been a controversial topic discussed in recent years. The main cause for the contradictory findings of existing studies might be the missing consideration of the storage time of red blood cell units (BUs), donor age, and gender matching. STUDY DESIGN AND METHODS: We retrospectively analyzed BCa patients who underwent RC in our department between 2004 and 2021. We excluded patients receiving BUs before RC, >10 BUs, or RC in a palliative setting. We assessed the effect of blood donor characteristics and storage time on overall survival (OS) and cancer-specific survival (CSS) through univariate and multivariable Cox regression analysis. We also performed a propensity score matching with patients who received BUs and patients who did not on a 1:1 ratio. RESULTS: We screened 1692 patients and included 676 patients for the propensity score matching. In the multivariable analysis, PBT was independently associated with worse OS and CSS (p < .001). Postoperative transfusions were associated with better OS (p = .004) and CSS (p = .008) compared to intraoperative or mixed transfusions. However, there was no influence of blood donor age, storage time, or gender matching on prognosis. DISCUSSION: In our study of BCa patients undergoing RC, we demonstrate that PBT, especially if administered intraoperatively, is an independent risk factor for a worse prognosis. However, storage time, donor age, or gender matching did not negatively affect oncological outcomes. Therefore, the specific selection of blood products does not promise any benefits.

Berbamine targets cancer stem cells and reverses cabazitaxel resistance via inhibiting IGF2BP1 and p-STAT3 in prostate cancer.

BACKGROUND: Cancer stem cells (CSCs) are a small subpopulation of tumor cells with the capability of self-renewal and drug resistance, leading to tumor progression and disease relapse. Our study aimed to investigate the antitumor effect of berbamine, extracted from berberis amurensis, on prostate CSCs. METHODS: Sphere formation was used to collect prostate CSCs. The viability, proliferation, invasion, migration, and apoptosis assays were used to evaluate the antitumor effect of berbamine on prostate CSCs. Prostate CSC markers were analyzed by flow cytometry and qRT-PCR. Small RNA sequencing analysis was conducted to analyse miRNAs. Exosomes were extracted using the ExoQuick-TC kit and verified by testing exosomal markers using western blot. RESULTS: Berbamine targets prostate CSCs. Additionally, berbamine enhanced the antitumor effect of cabazitaxel, a second-line chemotherapeutic drug for advanced prostate cancer, and re-sensitized Cabazitaxel-resistant PCa cells (CabaR-DU145) to cabazitaxel by inhibiting ABCG2, CXCR4, IGF2BP1, and p-STAT3. Berbamine enhanced the expression of let-7 miRNA family and miR-26b and influenced the downstream targets IGF2BP1 and p-STAT3, respectively. Silencing CXCR4 and ABCG2 downregulated the expression of IGF2BP1 and p-STAT3, respectively. Importantly, berbamine enhanced also levels of exosomal let-7 family and miR-26b, suggesting that berbamine possibly influences the expression of let-7 family and miR-26b through exosome delivery. Exosomes derived from berbamine-treated CabaR-DU145 cells re-sensitized the cells to cabazitaxel. CONCLUSION: Berbamine enhanced the toxic activity of cabazitaxel and reversed cabazitaxel resistance potentially through CXCR4/exosomal let-7/IGF2BP1 and ABCG2/exosomal miR-26b/p-STAT3 axes.

Added value of randomised biopsy to multiparametric magnetic resonance imaging-targeted biopsy of the prostate in a contemporary cohort.

OBJECTIVE: To assess the added value of concurrent systematic randomised ultrasonography-guided biopsy (SBx) to multiparametric magnetic resonance imaging (mpMRI)-targeted biopsy and the additional rate of overdiagnosis of clinically insignificant prostate cancer (ciPCa) by SBx in a large contemporary, real-world cohort. PATIENTS AND METHODS: A total of 1552 patients with positive mpMRI and consecutive mpMRI-targeted biopsy and SBx were enrolled. Added value and the rate of overdiagnosis by SBx was evaluated. PRIMARY OUTCOME: added value of SBx, defined as detection rate of clinically significant PCa (csPCa; International Society of Urological Pathology [ISUP] Grade ≥2) by SBx, while mpMRI-targeted biopsy was negative or showed ciPCa (ISUP Grade 1). SECONDARY OUTCOME: rate of overdiagnosis by SBx, defined as detection of ciPCa in patients with negative mpMRI-targeted biopsy and PSA level of <10 ng/mL. RESULTS: Detection rate of csPCa by mpMRI-targeted biopsy and/or SBx was 753/1552 (49%). Added value of SBx was 145/944 (15%). Rate of overdiagnosis by SBx was 146/656 (22%). Added value of SBx did not change when comparing patients with previous prostate biopsy and biopsy naïve patients. In multivariable analysis, a Prostate Imaging-Reporting and Data System (PI-RADS) 4 index lesion (odds ratio [OR] 3.19, 95% confidence interval [CI] 1.66-6.78; P = 0.001), a PI-RADS 5 index lesion (OR 2.89, 95% CI 1.39-6.46; P = 0.006) and age (OR 1.05, 95% CI 1.03-1.08; P < 0.001) were independently associated with added value of SBx. CONCLUSIONS: In our real-world analysis, we saw a significant impact on added value and added rate of overdiagnosis by SBx. Subgroup analysis showed no significant decrease of added value in any evaluated risk group. Therefore, we do not endorse omitting concurrent SBx to mpMRI-guided biopsy of the prostate.

The Characterization of Non-oncologic Chronic Drug Therapy in Bladder Cancer Patients and the Impact on Recurrence-Free and Cancer-Specific Survival: A Prospective Study.

We aimed to characterize non-oncologic chronic drug therapy of bladder cancer (BC) patients and evaluate a possible impact on recurrence-free (RFS) and cancer-specific survival (CSS). Patients with a first diagnosis (FD) of BC or radical cystectomy (RC) were included in a prospective, monocentric, observational study. Drugs and medical data was assessed at start and three-monthly for 24 months. Drugs were classified by anatomical-therapeutic-chemical code (ATC). Endpoints for outcome analysis were RFS and CSS in univariate (Kaplan-Meier curves and log-rank test, Cox regression for Hazard Ratio (HR)) and multivariate (Cox regression models) analyses. Of 113 patients, 52 had FD and 78 RC. Median age was 74 and 72 years, 83% and 82% were male. Drugs of 114 ATC classes were taken by 48 (92%) FD patients (median number 4.5/IQR 2-7.5) and 73 (94%) of RC patients (median 5/IQR 2-9). In univariate analysis (log-rank test (p)/Cox regression (HR, 95% CI, p)), polypharmacy (p = 0.036/HR = 2.83, 95% CI = 1.02-7.90, p = 0.047), calcium channel blockers (p = 0.046/HR = 2.47, 95% CI = 0.97-6.27, p = 0.057) and proton pump inhibitors (p = 0.015/HR = 3.16, 95% CI = 1.18-8.41, p = 0.022) had a significant negative impact on RFS in RC patients, statins (p = 0.025/HR = 0.14, 95% CI = 0.02-1.06, p = 0.057) a positive effect on RFS in FD patients, angiotensin-converting enzyme inhibitors (p = 0.008/HR = 10.74, 95% CI = 1.20-96.17, p = 0.034) and magnesium (p = 0.042/HR = 5.28, 95% CI = 0.88-31.59, p = 0.067) a negative impact on CSS in FD patients. In multivariate analysis, the only significant drug effects were the negative impact of angiotensin-converting enzyme inhibitors (HR = 15.20, 95% CI = 1.30-177.67, p = 0.030) and magnesium (HR = 22.87, 95% CI = 1.57-333.81), p = 0.022) on CSS in FD patients, and the positive impact of statins (HR = 0.12, 95% CI = 0.01-0.97, p = 0.047) on RFS in FD patients. Impact of non-oncologic drugs on RFS and CSS was small in this prospective study. Thus, appropriate treatment of comorbidities is encouraged.

Patients' Trust in Artificial Intelligence-based Decision-making for Localized Prostate Cancer: Results from a Prospective Trial.

BACKGROUND: Artificial intelligence (AI) has the potential to enhance diagnostic accuracy and improve treatment outcomes. However, AI integration into clinical workflows and patient perspectives remain unclear. OBJECTIVE: To determine patients' trust in AI and their perception of urologists relying on AI, and future diagnostic and therapeutic AI applications for patients. DESIGN, SETTING, AND PARTICIPANTS: A prospective trial was conducted involving patients who received diagnostic or therapeutic interventions for prostate cancer (PC). INTERVENTION: Patients were asked to complete a survey before magnetic resonance imaging, prostate biopsy, or radical prostatectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was patient trust in AI. Secondary outcomes were the choice of AI in treatment settings and traits attributed to AI and urologists. RESULTS AND LIMITATIONS: Data for 466 patients were analyzed. The cumulative affinity for technology was positively correlated with trust in AI (correlation coefficient 0.094; p = 0.04), whereas patient age, level of education, and subjective perception of illness were not (p > 0.05). The mean score (± standard deviation) for trust in capability was higher for physicians than for AI for responding in an individualized way when communicating a diagnosis (4.51 ± 0.76 vs 3.38 ± 1.07; mean difference [MD] 1.130, 95% confidence interval [CI] 1.010-1.250; t924 = 18.52, p < 0.001; Cohen's d = 1.040) and for explaining information in an understandable way (4.57 ± vs 3.18 ± 1.09; MD 1.392, 95% CI 1.275-1.509; t921 = 27.27, p < 0.001; Cohen's d = 1.216). Patients stated that they had higher trust in a diagnosis made by AI controlled by a physician versus AI not controlled by a physician (4.31 ± 0.88 vs 1.75 ± 0.93; MD 2.561, 95% CI 2.444-2.678; t925 = 42.89, p < 0.001; Cohen's d = 2.818). AI-assisted physicians (66.74%) were preferred over physicians alone (29.61%), physicians controlled by AI (2.36%), and AI alone (0.64%) for treatment in the current clinical scenario. CONCLUSIONS: Trust in future diagnostic and therapeutic AI-based treatment relies on optimal integration with urologists as the human-machine interface to leverage human and AI capabilities. PATIENT SUMMARY: Artificial intelligence (AI) will play a role in diagnostic decisions in prostate cancer in the future. At present, patients prefer AI-assisted urologists over urologists alone, AI alone, and AI-controlled urologists. Specific traits of AI and urologists could be used to optimize diagnosis and treatment for patients with prostate cancer.

The Impact of Laser Energy on Functional Outcome Following Holmium Laser Enucleation of the Prostate.

OBJECTIVE: To assess the impact of total laser energy applied, as well as enucleation efficiency on short-term functional outcomes for patients treated for lower urinary tract symptoms (LUTS) with Holmium laser enucleation of the prostate (HoLEP). METHODS: A retrospective analysis of 1593 consecutive patients who underwent HoLEP for LUTS due to benign prostate obstruction in a tertiary care center between January 2018 and January 2021 was performed. Perioperative parameters and short-term functional outcome were evaluated. Spearman's rank correlation and linear regression analysis was applied to identify the relationship between total laser energy applied or enucleation efficiency and functional outcome (P < .05). RESULTS: Median weight of enucleated tissue was 65g, median tissue retrieval percentage was 72.2% and median surgery speed was 0.8g/min. Median laser energy applied was 48.8 kJ, median enucleation efficiency was 1.4g/kJ. No significant correlation between the total laser energy and postoperative International Prostate Symptom Score (IPSS), peak urinary flow (Qmax) or postvoid residual urine volume (PVR) was found (P-range: .473-.969). Likewise, no correlation was found between enucleation efficiency and postoperative IPSS, Qmax, and PVR (P-range: .080-.932). Perioperative improvement of functional outcome (delta IPSS, delta Qmax, and delta PVR) did not correlate with total laser energy applied (P-range: .211-.785) or with enucleation efficiency (P-range: .118-.543). Those results were confirmed in linear regression analysis. CONCLUSION: The results of this study reveal that functional outcome following HoLEP are not dependant on the amount of laser energy applied or enucleation efficiency. Our results should support the increased use of HoLEP as surgical treatment option for LUTS due to BPH.

Identification of a novel combination treatment strategy in clear cell renal cell carcinoma stem cells with shikonin and ipilimumab.

Background: Management of clear cell renal cell carcinoma (ccRCC) has changed rapidly in recent years with the advent of immune checkpoint inhibitors (ICIs). However, only a limited number of patients can sustainably respond to immune checkpoint inhibitors and many patients develop resistance to therapy, creating an additional need for therapeutic strategies to improve the efficacy of systemic therapies. Methods: Binding probability and target genes prediction using online databases, invasion, migration, and apoptosis assays as well as the inhibition of cancer stem cells (CSCs) markers in ccRCC cell lines were used to select the most promising phytochemicals (PTCs). Mixed lymphocyte tumor cell culture (MLTC) system and flow cytometry were performed to confirm the potential combination strategy. The potential immunotherapeutic targets and novel CSC markers were identified via the NanoString analysis. The mRNA and protein expression, immune signatures as well as survival characteristics of the marker in ccRCC were analyzed via bioinformation analysis. Results: Shikonin was selected as the most promising beneficial combination partner among 11 PTCs for ipilimumab for the treatment of ccRCC patients due to its strong inhibitory effect on CSCs, the significant reduction of FoxP3+ Treg cells in peripheral blood mononuclear cells (PBMCs) of patients and activation of the endogenous effector CD3+CD8+ and CD3+CD4+ T cells in response to the recognition of tumor specific antigens. Based on NanoString analysis VCAM1, CXCL1 and IL8 were explored as potential immunotherapeutic targets and novel CSC markers in ccRCC. The expression of VCAM1 was higher in the tumor tissue both at mRNA and protein levels in ccRCC compared with normal tissue, and was significantly positively correlated with immune signatures and survival characteristics in ccRCC patients. Conclusion: We propose that a combination of shikonin and ipilimumab could be a promising treatment strategy and VCAM1 a novel immunotherapeutic target for the treatment of ccRCC.

The impact of previous inguinal mesh hernioplasty on oncological and patient-reported outcomes following radical prostatectomy.

BACKGROUND: The impact of previous inguinal mesh hernioplasty (MH) with non-resorbable mesh prostheses on surgical performance of radical prostatectomy (RP) has been controversially discussed, with unknown impact of MH on oncologic outcomes and health-related quality of life (HRQOL) following RP. We therefore aimed to assess the influence of previous MH on metastasis-free survival (MFS), biochemical recurrence-free survival (BRFS), and HRQOL following RP. METHODS: We identified 344 patients with previous MH prior RP within our prospectively assessed institutional database of 6275 patients treated with RP for PC (2008-2019). A 1:3 propensity-score matched analysis of 1345 men (n = 319 previous MH, n = 1026 no previous MH) was conducted. Primary endpoint was MFS and secondary endpoints were BRFS and HRQOL (based on EORTC QLQ-C30). Binary logistic regression, Kaplan-Meier, and Cox regression models tested the effect of previous MH on MFS, BRFS, and HRQOL (p < 0.05). RESULTS: Median follow-up was 47 months. Patients with previous MH had significantly lower 5-year MFS (72% vs. 85%, p < 0.001) and 5-year BRFS estimates (43% vs. 57%, p < 0.001). In multivariate analysis, previous MH was confirmed as an independent predictor for impaired MFS (hazard ratio [HR]: 3.772, 95% CI 1.12-12.64, p = 0.031) and BRFS (HR: 1.862, 95% CI: 1.22-2.85, p = 0.004). These results held true if stratified for surgical approach or limited to patients with successful PLND. We found significantly shorter median time to continence recovery for patients without previous MH (p = 0.001) without significant differences in total continence recovery rates, erectile function recovery, and HRQOL. CONCLUSIONS: Our findings show an impaired oncologic outcome for patients with previous MH following RP with no significant differences regarding continence recovery, erectile function recovery, and general HRQOL.

Associations of flow disruptions with patient, staff, and process outcomes: a prospective observational study of robotic-assisted radical prostatectomies.

BACKGROUND: Technological advancements in the operating room (OR) have sparked new challenges for surgical workflow, OR professionals, and patient safety. Disruptive events are frequent across all surgical specialties, but little is known about their effects on patient outcomes and the influence of systemic factors. The aim was to explore the associations of intraoperative flow disruptions (FDs) with patient outcomes, staff workload, and surgery duration. METHODS: Prospective, single-center, and multi-source study comprising direct and standardized OR observations of urologic surgical procedures, clinical patient outcomes, and staff- and patient-reported outcome data (PROMs; 3-month follow-up). All data were recorded between 01/2020 and 10/2021. FDs were assessed using standardized procedure observations. Linear and logistic regression analyses including multiple system factors were used to explore the effects of FDs on surgical outcomes. RESULTS: 61 robotic-assisted radical prostatectomy procedures were captured (with 61 patients and 243 staff reports). High rates of FDs were observed; however, our analyses did not show significant relationships with patient complication rates. Equipment- and patient-related FDs were associated with increased staff workload. No association was found between higher rates of FDs and procedure duration. CONCLUSIONS: FDs were not related to inferior patient outcomes. Our findings may inform future OR investigations that scrutinize the complex interplay of human, team, process, and technological components that mitigate the effects of FDs during surgery.

Methylation status of various gene loci in localized prostate cancer: Novel biomarkers for diagnostics and biochemical recurrence.

BACKGROUND: Oncologic outcomes for patients with localized prostate cancer (PCa) undergoing radical prostatectomy (RP) can vary widely. Hypermethylation of tumor-associated genes has potential as a novel diagnostic tool and predictive biomarker in PCa. We investigated the methylation status of tumor-associated genes in patients who underwent RP. METHODS: Patients who underwent RP during 2004 to 2008 were matched retrospectively based on post-operative D'Amico risk stratification. Quantitative pyrosequencing was used to analyze methylation status of 10 gene loci in cancerous and adjacent benign tissue from histological specimen. Follow-up was performed according to EAU guideline recommendations. Statistical analyses were performed to correlate methylation levels in cancerous and benign tissue with risk profiles and biochemical recurrence (BCR). RESULTS: The cohort included 71 patients: 22 low-risk, 22 intermediate-risk, and 27 high-risk. Mean follow-up time was 74 months. Methylation status differed significantly between cancerous and adjacent benign tissue for the 5 gene loci GSTP1, APC, RASSF1, TNFRFS10c, and RUNX3 (each P < 0.001). Also, the methylation level was significantly higher in high-risk than in low-risk patients for Endoglin2 and APC (P = 0.026; P = 0.032). Using ROC analysis, hypermethylation of APC in PCa tissue was associated with higher risk of BCR (P = 0.005). CONCLUSION: Methylation status of various gene loci holds diagnostic and predictive potential in PCa. Hypermethylation of APC, RASSF1, TNFRFS10c and RUNX3 were identified as novel PCa-specific biomarkers. Furthermore, increased methylation levels of APC and Endoglin2 were associated with high-risk PCa. Additionally, hypermethylation of APC was associated with increased risk of BCR after RP.

Interstitial Photodynamic Therapy of Glioblastomas: A Long-Term Follow-up Analysis of Survival and Volumetric MRI Data.

BACKGROUND: The treatment of glioblastomas, the most common primary malignant brain tumors, with a devastating survival perspective, remains a major challenge in medicine. Among the recently explored therapeutic approaches, 5-aminolevulinic acid (5-ALA)-mediated interstitial photodynamic therapy (iPDT) has shown promising results. METHODS: A total of 16 patients suffering from de novo glioblastomas and undergoing iPDT as their primary treatment were retrospectively analyzed regarding survival and the characteristic tissue regions discernible in the MRI data before treatment and during follow-up. These regions were segmented at different stages and were analyzed, especially regarding their relation to survival. RESULTS: In comparison to the reference cohorts treated with other therapies, the iPDT cohort showed a significantly prolonged progression-free survival (PFS) and overall survival (OS). A total of 10 of 16 patients experienced prolonged OS (≥ 24 months). The dominant prognosis-affecting factor was the MGMT promoter methylation status (methylated: median PFS of 35.7 months and median OS of 43.9 months) (unmethylated: median PFS of 8.3 months and median OS of 15.0 months) (combined: median PFS of 16.4 months and median OS of 28.0 months). Several parameters with a known prognostic relevance to survival after standard treatment were not found to be relevant to this iPDT cohort, such as the necrosis-tumor ratio, tumor volume, and posttreatment contrast enhancement. After iPDT, a characteristic structure (iPDT remnant) appeared in the MRI data in the former tumor area. CONCLUSIONS: In this study, iPDT showed its potential as a treatment option for glioblastomas, with a large fraction of patients having prolonged OS. Parameters of prognostic relevance could be derived from the patient characteristics and MRI data, but they may partially need to be interpreted differently compared to the standard of care.

Intratumoral Heterogeneity of Molecular Subtypes in Muscle-invasive Bladder Cancer-An Extensive Multiregional Immunohistochemical Analysis.

BACKGROUND: Molecular bladder cancer (BC) subtypes define distinct biological entities and were shown to predict treatment response in neoadjuvant and adjuvant settings. The extent of intratumoral heterogeneity (ITH) might affect subtyping of individual patients. OBJECTIVE: To comprehensively assess the ITH of molecular subtypes in a cohort of muscle-invasive BC. DESIGN, SETTING, AND PARTICIPANTS: A total of 251 patients undergoing radical cystectomy were screened. Three cores of the tumor center (TC) and three cores of the invasive tumor front (TF) of each patient were assembled in a tissue microarray. Molecular subtypes were determined employing 12 pre-evaluated immunohistochemical markers (FGFR3, CCND1, RB1, CDKN2A, KRT5, KRT14, FOXA1, GATA3, TUBB2B, EPCAM, CDH1, and vimentin). A total of 18 072 spots were evaluated, of which 15 002 spots were assessed based on intensity, distribution, or combination. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Allocation to one of five different molecular subtypes-urothelial like, genomically unstable, small-cell/neuroendocrine like, basal/squamous cell carcinoma like, and mesenchymal like-was conducted for each patient for the complete tumor, individual cores, TF, and TC separately. The primary objective was to assess the ITH between the TF and TC (n = 208 patients). The secondary objective was the evaluation of multiregion ITH (n = 191 patients). An analysis of the composition of ITH cases, association with clinicopathological parameters, and prognosis was conducted. RESULTS AND LIMITATIONS: ITH between the TF and TC was seen in 12.5% (n = 26/208), and ITH defined by at least two different subtypes of any location was seen in 24.6% (n = 47/191). ITH was more frequent in locally confined (pT2) versus advanced (pT ≥3) BC stages (38.7% vs 21.9%, p = 0.046), and pT4 BC presented with significantly more basal subtypes than pT2 BC (26.2% vs 11.5%, p = 0.049). In our cohort, there was no association of subtype ITH with prognosis or accumulation of specific molecular subtypes in ITH cases. The key limitations were missing transcriptomic and mutational genetic validation as well as investigation of ITH beyond subtypes. CONCLUSIONS: Several molecular subtypes can be found in nearly every fourth case of muscle-invasive BC, when using immunohistochemistry. ITH must be given due consideration for subtype-guided strategies in BC. Genomic validation of these results is needed. PATIENT SUMMARY: Different molecular subtypes can be found in many cases of muscle-invasive bladder cancer. This might have implications for individualized, subtype-based therapeutic approaches.