Objectives: The observational ‘Feeling Hot’ study aims to evaluate the feasibility of employing overnight penile temperature measurements for the detection of nocturnal erections, thereby... Show moreObjectives: The observational ‘Feeling Hot’ study aims to evaluate the feasibility of employing overnight penile temperature measurements for the detection of nocturnal erections, thereby contributing to the advancement and modernization of a non-invasive diagnostic system for erectile dysfunction. Subjects/Patients and Methods: In this proof-of-concept study, 10 healthy men aged 20–25 were recruited, following the methodology outlined in the ‘Staying Hot’ study by Torenvlied et al. Participants underwent ambulatory overnight penile temperature measurements concurrent with RigiScan recordings. Key outcome measures included baseline and peak penile temperatures during RigiScan-annotated nocturnal erections. Reference measurements of the thigh temperature were also taken to assess nocturnal temperature variations. Results: Statistically significant penile temperature increases (p = 0.008, n = 9) were observed during nocturnal erections, with an average elevation of 1.47C noted during the initial erections. This underscores the practical utility of penile temperature measurements in detecting erection onset. Challenges arose in accurately determining erection duration and subsequent erection onsets due to the persistence of elevated temperatures following initial erections, termed the ‘Staying Hot effect’. Reference thigh temperature measurements aided in addressing this challenge. Conclusion: Examining overnight penile temperature alongside simultaneous RigiScan recordings has yielded valuable insights into the viability of using the temperature methodology for detecting nocturnal erections. The ‘Feeling Hot’ study findings demonstrate significant penile temperature elevation during nocturnal erections in healthy young men, highlighting the potential of integrating this measurement methodology into the design of a modernized tool for ambulatory erectile dysfunction diagnostics. Further development of an advanced sensor system to comprehensively assess erection duration and quality is essential for enhancing clinical applicability. Show less
Afscheidsrede uitgesproken door Prof.dr. R.C.M. Pelger bij gelegenheid van zijn emeritaat als hoogleraar op het gebied urologie aan de Universiteit Leiden op vrijdag 8 december 2023
Non-metastatic prostate cancer (PCa) patients are at increased risk for osteoporosis and fractures mainly due to androgen deprivation therapy (ADT)-associated hypogonadism, but this remains largely... Show moreNon-metastatic prostate cancer (PCa) patients are at increased risk for osteoporosis and fractures mainly due to androgen deprivation therapy (ADT)-associated hypogonadism, but this remains largely underdiagnosed and untreated. In this study, we examine the value of pre-screening calcaneal QUS in identifying patients who should be referred for screening for osteoporosis using dual-energy X-Ray absorptiometry (DXA). In a single-center retrospective cross-sectional cohort study, we analysed data on DXA and calcaneal QUS measurements systematically collected between 2011 and 2013 in all non-metastatic PCa patients attending our Uro-Oncological Clinic at the Leiden University Medical Center. Receiver operating characteristic curves were used to assess the positive (PPV) and negative (NPV) predictive values of QUS T-scores of 0, -1.0, and - 1.8 in identifying DXAdiagnosed osteoporosis (T-scores < - 2.5 and < -2) at lumbar spine and/or femoral neck. Complete sets of data were available in 256 patients, median age 70.9 (53.6-89.5) years; 93.0 % had received local treatment, 84.4 % with additional ADT. Prevalence of osteoporosis and osteopenia was respectively 10.5 % and 53 %. Mean QUS Tscore was -0.54 +/- 1.58. Whereas PPV at any QUS T-score was <25 %, precluding the use of QUS as surrogate for DXA in screening for osteoporosis, QUS T-scores of -1.0 to 0.0 had a NPV of >= 94.5 % for DXA T-scores < 2.5 and < -2 at any site, confidently identifying patients least likely to have osteoporosis, thereby significantly reducing the number of patients requiring DXA screening for diagnosing osteoporosis by up to two-third. Osteoporosis screening is a significant unmet need in non-metastatic prostate cancer patients treated with ADT, and QUS may represent a valuable alternative pre-screening strategy to overcome logistics, time demands, and economic barriers encountered with current strategies for osteoporosis screening in these patients. Summary: Osteoporosis and associated increased fracture risk are common in non-metastatic prostate carcinoma, mainly due to androgen deprivation therapy, but these often remain underdiagnosed and untreated. We demonstrate that QUS is a safe, less costly pre-screen tool that reduces by up to two-third the number of patients requiring referral for DXA for osteoporosis screening. Show less
Background Chronic anal fissure is a common benign anorectal disease with a high recurrence rate. Pelvic floor physical therapy has been proven effective in the short-term management in patients... Show moreBackground Chronic anal fissure is a common benign anorectal disease with a high recurrence rate. Pelvic floor physical therapy has been proven effective in the short-term management in patients with chronic anal fissure and pelvic floor dysfunction (PAF-trial). The aim of this study was to determine the outcomes of the PAF-trial and fissure recurrence in patients who completed the 2 months of pelvic floor physical therapy at 1-year follow-up.Methods Electromyographic registration of the pelvic floor, digital rectal examination, visual analog scales, patient-related outcome measurements, and quality of life were assessed at baseline and at 1-year after inclusion. The primary outcome was muscle tone at rest during electromyographic registration of the pelvic floor at baseline and at 1-year follow-up. Secondary outcomes contained fissure recurrence, pain ratings, pelvic floor dysfunction, complaint reduction measured with a proctology specific patient-reported outcome measurement, and quality of life.Results The treatment protocol was followed by 133 patients. Ninety-seven patients (71%) completed the 1-year follow-up, 48 women (49.5%) and 49 men (50.5%) with a mean age of 44.4 +/- 11.6 years (range 19-68). In the total group of patients, mean resting electromyographic values of the pelvic floor significantly improved from baseline to follow-up at 1 year (mean estimated difference 2.20 mu V; 95% CI, 1.79 to 2.61; p < 0.001). After 1 year, the fissure recurred in 15 patients (15.5%). VAS-pain significantly decreased from baseline to follow-up (mean estimated difference 4.16; 95% CI, 3.75 to 4.58; p < 0.001). Dyssynergia was found in 72.9% at baseline and decreased to 14.4% at 1-year follow-up (p < 0.001). Complaint reduction measured with the Proctoprom significantly improved from baseline to 1-year follow-up (p < 0.001). Quality of life (RAND-36) significantly improved in eight of nine domains at 1-year follow-up. No significant improvement was found in the domain vitality.Conclusions In the PAF-trial, we demonstrated that pelvic floor physical therapy yields a significant and clinical benefit in the time course and therefore should be advocated as adjuvant conservative treatment in patients with chronic anal fissure. Show less
ObjectiveTo develop a standardised tool to evaluate flexible ureterorenoscopes (fURS).Materials and MethodsA three-stage consensus building approach based on the modified Delphi technique was... Show moreObjectiveTo develop a standardised tool to evaluate flexible ureterorenoscopes (fURS).Materials and MethodsA three-stage consensus building approach based on the modified Delphi technique was performed under guidance of a steering group. First, scope- and user-related parameters used to evaluate fURS were identified through a systematic scoping review. Then, the main categories and subcategories were defined, and the expert panel was selected. Finally, a two-step modified Delphi consensus project was conducted to firstly obtain consensus on the relevance and exact definition of each (sub)category necessary to evaluate fURS, and secondly on the evaluation method (setting, used tools and unit of outcome) of those (sub)categories. Consensus was reached at a predefined threshold of 80% high agreement.ResultsThe panel consisted of 30 experts in the field of endourology. The first step of the modified Delphi consensus project consisted of two questionnaires with a response rate of 97% (n = 29) for both. Consensus was reached for the relevance and definition of six main categories and 12 subcategories. The second step consisted of three questionnaires (response rate of 90%, 97% and 100%, respectively). Consensus was reached on the method of measurement for all (sub)categories.ConclusionThis modified Delphi consensus project reached consensus on a standardised grading tool for the evaluation of fURS – The Uniform grading tooL for flexIble ureterorenoscoPes (TULIP) tool. This is a first step in creating uniformity in this field of research to facilitate future comparison of outcomes of the functionality and handling of fURS. Show less
Background: Chronic anal fissure is one of the most common anorectal diseases and is associated with reduced quality of life. The aim of this study was to investigate the effects of pelvic floor... Show moreBackground: Chronic anal fissure is one of the most common anorectal diseases and is associated with reduced quality of life. The aim of this study was to investigate the effects of pelvic floor physical therapy on quality of life in patients with chronic anal fissure using the Short-Form 36 Health Survey (RAND-36). Methods: Adult patients, with chronic anal fissure and concomitant pelvic floor dysfunction, such as dyssynergia and increased pelvic floor muscle tone, were recruited at the Proctos Clinic in the Netherlands, between December 2018 and July 2021 and randomly assigned to an intervention group, receiving 8 weeks of pelvic floor physical therapy or assigned to a control group receiving postponed pelvic floor physical therapy (PAF trial). Quality of life and pain ratings were outcomes of the study and were measured at 8- and 20-week follow-up. Results: One hundred patients (50 women and 50 men, median age 44.6 years [range 19-68 years]), completed the RAND-36 questionnaire and visual analog (VAS) pain scale score at admission. A significant improvement was found at 20-week follow-up in all domains of the RAND-36; physical functioning, pain, health change (p < 0.001); physical role, vitality, general health, social functioning, emotional role, mental health (p < 0.05). VAS pain was significantly reduced at 8 weeks (mean estimated difference 1.98; 95% CI 1.55-2.42, p < 0.001) and remained significant at 20-week follow-up (p < 0.001). The difference between the groups as regards change in the mean pain intensity scores at 8 weeks was 2.48 (95% CI - 3.20 to - 1.75; p < 0.001). Compared to the reference values of the general Dutch population, the patients in our study with a chronic anal fissure and pelvic floor dysfunction reported an impaired quality of life in 8 of 9 domains of the RAND-36. After treatment, significant lower scores were found in 2 out of 9 domains. Conclusions: The results of this study provide evidence that treatment by pelvic floor physical therapy improves quality of life and reduces pain, making it an important tool in management of chronic anal fissure and concomitant pelvic floor dysfunction. Show less
Kaptein, F.H.J.; Hulle, T. van der; Braken, S.J.E.; Gennep, E.J. van; Buijs, J.T.; Burgmans, M.C.; ... ; Klok, F.A. 2022
BACKGROUND Renal cell carcinoma (RCC) can be complicated by a venous tumor thrombus (TT), of which the optimal management is unknown.OBJECTIVES This study sought to assess the prevalence of TT in... Show moreBACKGROUND Renal cell carcinoma (RCC) can be complicated by a venous tumor thrombus (TT), of which the optimal management is unknown.OBJECTIVES This study sought to assess the prevalence of TT in RCC, its current management, and its association with venous thromboembolism (VTE), arterial thromboembolism (ATE), major bleeding (MB), and mortality.METHODS Patients diagnosed with RCC between 2010 and 2019 in our hospital were included and followed from RCC diagnosis until 2 years after, or until an outcome of interest (VTE, ATE, and MB) or death occurred, depending on the analysis. Cumulative incidences were estimated with death as a competing risk. Cause-specific hazard models were used to identify predictors and the prognostic impact.RESULTS Of the 647 patients, 86 had a TT (prevalence 13.3%) at RCC diagnosis, of which 34 were limited to the renal vein, 37 were limited to the inferior vena cava below the diaphragm, and 15 extended above the diaphragm; 20 patients started therapeutic anticoagulation and 45 underwent thrombectomy with/without anticoagulation. During follow-up (median 24.0 [IQR: 7.0-24.0] months), 17 TT patients developed a VTE, 0 developed an ATE, and 11 developed MB. TT patients were more often diagnosed with VTE (adjusted HR: 6.61; 95% CI: 3.18-13.73) than non-TT patients, with increasing VTE risks in more proximal TT levels. TT patients receiving anticoagulation still developed VTE (HR: 0.56; 95% CI: 0.13-2.48), at the cost of more MB events (HR: 3.44; 95% CI: 0.95-12.42) compared with those without anticoagulation.CONCLUSIONS Patients with RCC-associated TT were at high risk of developing VTE. Future studies should establish which of these patients benefit from anticoagulation therapy. (c) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Show less
Background: A chronic anal fissure is a common, painful condition with great impact on daily life. The exact pathogenesis has not been fully elucidated and treatment varies. A large percentage of... Show moreBackground: A chronic anal fissure is a common, painful condition with great impact on daily life. The exact pathogenesis has not been fully elucidated and treatment varies. A large percentage of patients experience pelvic floor dysfunction (dyssynergia and increased pelvic floor muscle tone). The aim of our study was to investigate the effect of pelvic floor physical therapy in patients with chronic anal fissure. Methods: Between December 2018 and July 2021, at the Proctos Clinic in the Netherlands, patients with chronic anal fissure and pelvic floor dysfunction were randomly assigned to an intervention group, receiving 8 weeks of pelvic floor physical therapy including electromyographic biofeedback or assigned to a control group receiving postponed pelvic floor physical therapy. The primary outcome was muscle tone at rest during electromyographic registration of the pelvic floor before and after pelvic floor physical therapy. Secondary outcomes contained healing of the fissure, pain ratings, improvement of pelvic floor function, and complaint reduction measured with a proctology-specific patient-reported outcome measurement. Endpoints were measured at 8- and 20-week follow-up. Results: One hundred forty patients were included in the study, 68 men (48.6%) and 72 women (51.4%) with a mean age of 44.5 +/- 11.1 (range 19-79) years. Mean resting electromyographic values of the pelvic floor in the intervention group significantly improved from pre- to post-treatment (p < 0.001) and relative to controls (mean estimated difference between groups - 1.88 mu V; 95% CI, - 2.49 to - 1.27 (p < 0.001) at first follow-up and remained significant from baseline at 20-week follow-up (p < 0.001). The intervention group performed better compared to the control group on all secondary outcomes, i.e., healing of the fissure (55.7% of the patients vs 21.4% in control, pain ratings (p < 0.001), diminished dyssynergia (p < 0.001), complaint reduction (p < 0.001), and decrease of pelvic floor muscle tone (p < 0.05) at first follow-up. Conclusions: The findings of this study provide strong evidence that pelvic floor physical therapy is effective in patients with chronic anal fissure and pelvic floor dysfunction and supports its recommendation as adjuvant treatment besides regular conservative treatment. Show less
Background Chronic anal fissure (CAF) is a common, bothersome condition frequently accompanied by pelvic floor complaints. Despite current guidelines, optimal management is challenging. The aim of... Show moreBackground Chronic anal fissure (CAF) is a common, bothersome condition frequently accompanied by pelvic floor complaints. Despite current guidelines, optimal management is challenging. The aim of this study is to evaluate current management of CAF among gastrointestinal surgeons in the Netherlands. Methods Dutch gastrointestinal surgeons and residents were sent a survey invitation by email, which was available online between June 2021 and September 2021. The questionnaire consisted of 21 questions concerning work experience, physical examination, diagnostic and surgical techniques, and follow-up. Results Overall, 106 (33%) respondents completed the survey. Most respondents (59%) had at least 10 years of experience in treating CAF. Only 23% always addressed pelvic floor complaints. Fifty-one percent performed digital rectal examination and 22% always, or almost always, examined the pelvic floor muscles. Most respondents started treatment with fibers and/or laxatives and ointment (96%). Diltiazem was in 90% the preferred ointment. Twenty-two percent referred patients for pelvic floor physical therapy. Botulinum toxin was in 54% performed under general or spinal anesthesia or sedation. The surgical procedure of choice was fissurectomy (71%) followed by lateral internal sphincterotomy (27%). Fissurectomy was in 51% always combined with botulinum toxin. Fifty-seven percent of the respondents preferred a physical follow-up appointment. Conclusion Guideline recommendations are largely followed in the Netherlands, starting with conservative measures followed by surgical procedures. Surgeons do not consistently assess pelvic floor complaints, nor do they routinely examine the pelvic floor muscles. Awareness of pelvic floor dysfunctions is important to refer patients for pelvic floor physical therapy. Show less
Background Anti-cancer drugs commonly adversely affect fertility and sexual function. Despite this, patients report a lack of counselling of these potential adverse effects. The aim was to... Show moreBackground Anti-cancer drugs commonly adversely affect fertility and sexual function. Despite this, patients report a lack of counselling of these potential adverse effects. The aim was to determine Dutch oncologists' knowledge about the adverse effects of various cancer drugs on fertility and sexual function. Methods A cross-sectional survey was sent to members of the Dutch Society for Medical Oncology (n = 433). The survey questions included various cancer drugs' adverse effects on fertility, ovulation, spermatogenesis, and sexual function. Results One hundred and five of 392 oncologists responded (26.8%). Oncologists were more aware of the adverse effects on fertility compared to sexual function. Drugs that were mostly believed to negatively affect fertility were cisplatin (n = 81, 80.2%), epirubicin (n = 78, 78.0%) and cyclophosphamide (n = 80, 77.7%). Regarding sexual function, most mentioned drugs were tamoxifen (n = 67, 65.7%), GnRH-agonists (n = 64, 63.4%) and cisplatin (n = 58, 57.4%). Oncologists with expertise in urology possessed more awareness regarding sexuality-related adverse effects (cisplatin p = 0.038, etoposide p = 0.025, ifosfamide p = 0.06, vinblastine p = 0.000). Conclusion Results revealed that oncologists have different beliefs about possible sexual and fertility-related adverse effects concerning medication resources and literature. Based on our results, oncologists do not possess sufficient knowledge to inform patients about sexual and fertility-related adverse effects. Show less
Seyrek, N.; Hollemans, E.; Osanto, S.; Pelger, R.C.M.; Poel, H.G. van der; Bekers, E.; ... ; Leenders, G.J.L.H. van 2021
Aims Gleason pattern 4 (GP4) percentage, invasive cribriform and/or intraductal carcinoma (IC/IDC) and the presence of tertiary Gleason pattern 5 (TP5) in radical prostatectomy (RP) specimens all... Show moreAims Gleason pattern 4 (GP4) percentage, invasive cribriform and/or intraductal carcinoma (IC/IDC) and the presence of tertiary Gleason pattern 5 (TP5) in radical prostatectomy (RP) specimens all aid in the risk stratification of Grade Group (GG) 2 prostate cancer patients. However, it is unclear to what extent these pathological features are mutually related and what are their individual values if they are investigated simultaneously. The aims of this study were: (i) to determine the mutual relationships of the GP4 percentage, IC/IDC and TP5 in GG2 RP specimens; and (ii) to assess their prognostic value for biochemical recurrence-free survival (BCRFS). Methods and results Of 1064 RP specimens, 472 (44.4%) showed GG2 prostate cancer. Patients with >= 25% GP4 more frequently had IC/IDC (67.0% versus 43.9%; P < 0.001) and TP5 (20.6% versus 5.8%; P < 0.001) than those with <25% GP4. In unadjusted analysis, an increased GP4 percentage [hazard ratio (HR) 1.3; 95% confidence interval (CI) 1.0-1.6; P = 0.04] and IC/IDC (log rank P < 0.001) were associated with shorter BCRFS, whereas TP5 (P = 0.12) and a dichotomised (<25%, >= 25%) GP4 percentage (P = 0.10) were not. In multivariable analysis, IC/IDC was an independent prognostic factor (HR 1.9; 95% CI 1.2-2.9; P = 0.005) for BCRFS, whereas a continuous or dichotomised GP4 percentage and TP5 were not independent prognostic factors. Conclusion In conclusion, a higher GP4 percentage in RP specimens was associated with more frequent IC/IDC and TP5. IC/IDC was an independent predictor for BCRFS, whereas the GP4 percentage and TP5 were not. These findings underscore the importance of routinely including the presence of IC/IDC in RP pathology reports. Show less
Background: Chronic anal fissure (CAF) is a common cause of severe anorectal pain with a high incidence rate. Currently, a wide range of treatment options are available with recurrence rates... Show moreBackground: Chronic anal fissure (CAF) is a common cause of severe anorectal pain with a high incidence rate. Currently, a wide range of treatment options are available with recurrence rates varying between 7 and 42%. Pelvic floor physical therapy (PFPT) is a treatment option for increased pelvic floor muscle tone and dyssynergia which often accompanies CAF. However, literature on this subject is scarce. The Pelvic Floor Anal Fissure (PAF)-study aims to determine the efficacy and effectiveness of PFPT on improvement on pelvic floor muscle tone and function, pain, healing of the fissure, quality of life and complaint reduction in patients with CAF.Methods: The PAF-study is a single-centre, two armed, randomized controlled trial. Patients with CAF and pelvic floor dysfunction are eligible for inclusion. Exclusion criteria include abscess, fistula, Crohn's disease, ulcerative colitis, anorectal malignancy, prior rectal radiation, and pregnancy. A total of 140 patients will be randomized for either PFPT or postponed treatment of PFPT.The primary outcome is tone at rest during electromyographic registration of the pelvic floor before and after therapy. Secondary outcomes consist of healing of the fissure, pain ratings, improvement of pelvic floor function, complaint reduction and quality of life. Primary and secondary endpoints are measured at 8 and 20 weeks and at 1-year follow-up.Discussion: Currently, there is a gap in treatment modalities between conservative management and surgery. This manuscript prescribes the rationale, design, and methodology of a randomized controlled trial investigating PFPT as a treatment option for patients with CAF. Show less
Cancer diagnosis and treatment may influence reproductive planning and impact fertility in patients of reproductive age. Although guidelines have been established in the past decade, education,... Show moreCancer diagnosis and treatment may influence reproductive planning and impact fertility in patients of reproductive age. Although guidelines have been established in the past decade, education, practice, and attitudes of medical oncologists regarding fertility preservation remain undecided. A nationwide survey was performed among members of the Dutch Society for Medical Oncology. Demographics, practice, knowledge, and barriers were measured regarding information provision of fertility preservation towards cancer patients of childbearing age. From 392 members, 120 oncologists completed the questionnaire (30.6%). Majority of oncologists was convinced it is their responsibility to discuss impact of cancer treatment to fertility (93.2%), yet 68.3% discussed the subject often or always (n = 82). Oncologists employed in district general hospitals were less likely to discuss fertility (p = 0.033). On average, 44.6% of reproductive men and 28.9% of reproductive women is referred to fertility specialists. Half of the respondents declared to possess sufficient knowledge regarding fertility preservation (n = 57, 47.5%). Poor prognosis (53%), unlikely survival (43.1%), and high chances on fertility recovery (28.7%) were identified as barriers to discussing fertility preservation. Among oncologists, impact of cancer treatment on fertility is a well-accepted responsibility to counsel. Despite, self-reported knowledge regarding fertility preservation is strongly varying. In practice, fertility is discussed to some extent, influenced by several barriers and depending on prognosis and type of hospital. Patients benefit from knowledge improvement among oncology care providers concerning fertility effects of cancer treatment. Education during medical school, residency, and among practicing oncologists may raise awareness, together with enhancement of referral possibilities. Show less
Objectives The objective of this study was to identify, map and review scope-related and user-related parameters used to evaluate the quality of flexible ureterorenoscopes. Thereby identifying key... Show moreObjectives The objective of this study was to identify, map and review scope-related and user-related parameters used to evaluate the quality of flexible ureterorenoscopes. Thereby identifying key items and variability in grading systems. Methods A literature search of four databases (MEDLINE [Ovid], EMBASE [Ovid], Web of Science, Google scholar and the Cochrane Library) was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines encompassing articles published up to August 2020. A total of 2386 articles were screened. Results A total of 48 articles were included in this systematic scoping review. All studies had a prospective design. Five key items in the assessment of flexible ureterorenoscopy were distinguished: 'Manoeuvrability' (87.5%), 'Optics' (64.6%), 'Irrigation' (56.3%), 'Handling' (39.6%) and 'Durability' (35.4%). After regrouping, every key item could be divided into specific subcategories. However, the quality assessment showed a wide variation in denomination, method of measurement, circumstances of measurement, tools used during measurements, number of measurements performed, number of observers, and units of outcomes. Conclusion The research field regarding quality assessment of ureterorenoscopes is heterogeneous. In this systematic scoping review we identified five key parameters: Manoeuvrability, Optics, Irrigation, Handling and Durability, used to grade flexible ureterorenoscopes. However, within these categories we found a wide variety in terms of method of measurements. A standardised, uniform grading tool is required to assess and compare the quality of flexible ureterorenoscopes in the future. Show less
Individual growth patterns and cribriform architecture are increasingly considered in risk stratification and clinical decision-making in men with prostate cancer. Our objective was to establish... Show moreIndividual growth patterns and cribriform architecture are increasingly considered in risk stratification and clinical decision-making in men with prostate cancer. Our objective was to establish the prognostic value of individual Gleason 5 patterns in a radical prostatectomy (RP) cohort. We reviewed 1064 RPs and recorded Grade Group (GG), pT-stage, surgical margin status, Gleason 4 and 5 growth patterns as well as intraductal carcinoma. The clinical endpoints were biochemical recurrence and post-operative distant metastasis. Gleason pattern 5 was present in 339 (31.9%) RPs, of which 47 (4.4%) presented as primary, 166 (15.6%) as secondary, and 126 (11.8%) as tertiary pattern. Single cells/cords were present in 321 (94.7%) tumors with Gleason pattern 5, solid fields in 90 (26.5%), and comedonecrosis in invasive carcinoma in 32 (9.4%) tumors. Solid fields demonstrated either a small nested morphology (n = 50, 14.7%) or medium to large solid fields (n = 61, 18.0%). Cribriform architecture was present in 568 (53.4%) RPs. Medium to large solid fields and comedonecrosis coincided with cribriform architecture in all specimens, and were not observed in cribriform-negative cases. In multivariable analysis adjusted for Prostate-Specific Antigen, pT-stage, GG, surgical margin status and lymph node metastases, cribriform architecture (Hazard Ratio (HR) 9.9; 95% Confidence Interval (CI) 3.9-25.5, P < 0.001) and comedonecrosis (HR 2.1, 95% CI 1.2-3.7, P = 0.01) were independent predictors for metastasis-free survival, while single cells/cords (HR 1.2; 95% CI 0.7-1.8, P = 0.55) and medium to large solid fields (HR 1.6, 95% CI 0.9-2.7, P = 0.09) were not. In conclusion, comedonecrosis in invasive carcinoma is an independent prognostic Gleason 5 pattern for metastasis-free survival after RP. These data support the current recommendations to routinely include cribriform pattern in pathology reports and indicate that comedonecrosis should also be commented on. Show less
Background Surgically induced nerve damage is a common but debilitating side effect in oncological surgery. With the aim to use fluorescence guidance to enable nerve-sparing interventions in future... Show moreBackground Surgically induced nerve damage is a common but debilitating side effect in oncological surgery. With the aim to use fluorescence guidance to enable nerve-sparing interventions in future surgery, a fluorescent tracer was developed that specifically targets myelin protein zero (P0). Results Truncated homotypic P0 protein-based peptide sequences were C-terminally functionalized with the far-red cyanine dye Cy5. The lead compound Cy5-P0(101-125) was selected after initial solubility, (photo)physical and in vitro evaluation (including P0-blocking experiments). Cy5-P0(101-125) (K-D = 105 +/- 17 nM) allowed in vitro and ex vivo P0-related staining. Furthermore, Cy5-P0(101-125) enabled in vivo fluorescence imaging of the Sciatic nerve in mice after local intravenous (i.v.) administration and showed compatibility with a clinical fluorescence laparoscope during evaluation in a porcine model undergoing robot-assisted surgery. Biodistribution data revealed that i.v. administered [In-111]In-DTPA-P0(101-125) does not enter the central nervous system (CNS). Conclusion P0(101-125) has proven to be a potent nerve-specific agent that is able to target P0/myelin under in vitro, ex vivo, and in vivo conditions without posing a threat for CNS-related toxicity. Show less
Baart, V.M.; Horst, G. van der; Deken, M.M.; Bhairosingh, S.S.; Schomann, T.; Sier, V.Q.; ... ; Sier, C.F.M. 2021
With a 5-year recurrence rate of 30-78%, urothelial cell carcinoma (UCC) rates amongst the highest of all solid malignancies. Consequently, after transurethral resection, patients are subjugated to... Show moreWith a 5-year recurrence rate of 30-78%, urothelial cell carcinoma (UCC) rates amongst the highest of all solid malignancies. Consequently, after transurethral resection, patients are subjugated to life-long endoscopic surveillance. A multimodal near-infrared (NIR) fluorescence-based imaging strategy can improve diagnosis, resection and surveillance, hence increasing quality of life.Methods: Expression of urokinase plasminogen activator receptor (uPAR) and epithelial cell adhesion molecule (EpCAM) are determined on paraffin-embedded human UCC using immunohistochemistry and on UCC cell lines by flow cytometry. MNPR-101, a humanised monoclonal antibody targeting uPAR is conjugated to IRDye800CW and binding is validated in vitro using surface plasmon resonance and cell-based binding assays. In vivo NIR fluorescence and photoacoustic three-dimensional (3D) imaging are performed with subcutaneously growing human UM-UC-31uc2 cells in BALB/c-nude mice. The translational potential is confirmed in a metastasising UM-UC-31uc2 orthotopic mouse model. InfliximabIRDye800CW and rituximab-IRDye800CW are used as controls.Results: UCCs show prominent uPAR expression at the tumour-stroma interface and EpCAM on epithelial cells. uPAR and EpCAM are expressed by 6/7 and 4/7 UCC cell lines, respectively. In vitro, MNPR-101-IRDye800CW has a picomolar affinity for domain 2-3 of uPAR. In vivo fluorescence imaging with MNPR-101-IRDye800CW, specifically delineates both subcutaneous and orthotopic tumours with tumour-to-background ratios reaching as high as 6.8, differing significantly from controls (p < 0.0001). Photoacoustic 3D in depth imaging confirms the homogenous distribution of MNPR-101-IRDye800CW through the tumour.Conclusions: MNPR-101-IRDye800CW is suitable for multimodal imaging of UCC, awaiting clinical translation. (C) 2021 The Author(s). Published by Elsevier Ltd. Show less
Manna, F. la; Menna, M. de; Patel, N.; Karkampouna, S.; Filippo, M.R. de; Klima, I.; ... ; Kruithof-de Julio, M. 2021
Simple SummaryTesticular cancer is the most common malignancy in young males affecting the ability to father children. It's important that effects on fertility are discussed before starting... Show moreSimple SummaryTesticular cancer is the most common malignancy in young males affecting the ability to father children. It's important that effects on fertility are discussed before starting treatment so patients are aware of the risks and their options. The objective of our study was to evaluate the manner in which men with testicular cancer are counselled about implications on fertility and the possibility of semen preservation. Furthermore, we aimed to evaluate satisfaction with provided information and to identify reproductive concerns. In a sample of 201 patients, one out of ten patients reported not to be informed about the risk of subfertility. Sperm banking was performed by 41.3%, of which 13 men made use of preserved sperm, resulting in paternity for 7 men. The subjects fertility and semen preservation need to be broached promptly after diagnosis of testicular cancer because they cause dissatisfaction with care and grief if fertility problems occur afterwards.Men with testicular cancer (TC) risk impaired fertility. Fertility is a major concern for TC patients due to diagnosis in almost always reproductive ages and high overall survival. This study assessed counselling in regards to the risk of impaired fertility and sperm cryopreservation. A cross-sectional survey was performed on 566 TC patients diagnosed between 1995-2015. Of the 566 survivors, 201 questionnaires were completed (35.5%). Eighty-eight percent was informed about possible impaired fertility, 9.5% was not informed. The majority (47.3%) preferred the urologist to provide information. Collecting sperm was troublesome but successful for 25.6%, 4.8% did not succeed in collecting sperm. The reasons were high pressure due to disease, pain after surgery and uncomfortable setting. Due to impaired fertility, 19% of the respondents reported grief and 9.3% stated as being less satisfied in life. Sperm cryopreservation was performed by 41.3% (n = 83). One third (n = 63, 31.3%) had children after treatment, of which 11.1% made use of preserved sperm (n = 7). The results of this survey indicate the importance of timely discussion of fertility issues with TC patients. While being discussed with most men, dissatisfaction and grief may occur as a result of impaired fertility and a lack of counselling. Overall, 6.5% made use of cryopreserved sperm (n = 13). Men prefer their urologist providing counselling on fertility. Show less
