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Low survival rates of metastatic cancers emphasize the need for a drug that can prevent and/or treat metastatic cancer. αv integrins are involved in essential processes for tumor growth and metastasis and targeting of αv integrins has been shown to decrease angiogenesis, tumor growth and metastasis. In this study, the role of αv integrin and its potential as a drug target in bladder cancer was investigated. Treatment with an αv integrin antagonist as well as knockdown of αv integrin in the bladder carcinoma cell lines, resulted in reduced malignancy in vitro, as illustrated by decreased proliferative, migratory and clonogenic capacity. The CDH1/CDH2 ratio increased, indicating a shift towards a more epithelial phenotype. This shift appeared to be associated with downregulation of EMT-inducing transcription factors including SNAI2. The expression levels of the self-renewal genes NANOG and BMI1 decreased as well as the number of cells with high Aldehyde Dehydrogenase activity. In addition, self-renewal ability decreased as measured with the urosphere assay. In line with these observations, knockdown or treatment of αv integrins resulted in decreased metastatic growth in preclinical in vivo models as assessed by bioluminescence imaging. In conclusion, we show that αv integrins are involved in migration, EMT and maintenance of Aldehyde Dehydrogenase activity in bladder cancer cells. Targeting of αv integrins might be a promising approach for treatment and/or prevention of metastatic bladder cancer.

Objectives 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 1.47°C 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.

Objectives Utilizing penile saturation and temperature measurements presents a promising avenue for the development of an innovative sensor system aimed at nocturnal erection detection. This study aims to determine the feasibility of erection detection with light reflection of haemoglobin (LRH), as a precursor for penile saturation measurements, as well as penile temperature by comparison with simultaneous overnight RigiScan measurements. Materials and Methods This is a proof‐of‐concept observational study on 10 healthy volunteers with a cross sectional design. A penile transdermal haemoglobin and temperature sensor was developed to measure penile LRH through real‐time monitoring with receiving photodiodes and emitting light‐emitting diode (LED). Besides statistical analysis on LRH, temperature and RigiScan data, a visual assessment was done to determine detectability of changes in the LRH and temperature course during the RigiScan‐annotated erections. Results A total of 40 nocturnal erections from 10 healthy volunteers were annotated with the RigiScan. The LRH values significantly increase during a nocturnal erection (p < 0.01) and penile temperature (p < 0.01). The largest elevation of temperature was seen in the last erection, with an increase of 0.94°C. The corrected temperature shows an increase of 1.29°C in the last erection. Furthermore, visual detectability was feasible for 80% of the erections with LRH values and 90% with the temperature output. Conclusion Penile LRH and temperature have the potential to serve as an alternative methodology for nocturnal erection detection compared with the currently applied circumference and rigidity measurements. This is an important step in the development of a patient‐friendly and modernized tool for erectile dysfunction diagnostics. An improved sensor should be developed to allow for calculation of saturation percentage from LRH values. In combination with penile temperature measurements, this allows for conduction of further validity studies to work towards translation into clinical practice for non‐invasive ED diagnostics.

The Gleason score is an important parameter for clinical outcome in prostate cancer patients. Gleason score 8 is a heterogeneous disease including Gleason score 3 + 5, 4 + 4, and 5 + 3 tumors, and encompasses a broad range of tumor growth patterns. Our objective was to characterize individual growth patterns and identify prognostic parameters in Gleason score 8 prostate cancer patients. We reviewed 1064 radical prostatectomy specimens, recorded individual Gleason 4 and 5 growth patterns as well as presence of intraductal carcinoma, and evaluated biochemical recurrence- and metastasis-free survival. Gleason score 8 disease was identified in 140 (13%) patients, of whom 76 (54%) had Gleason score 3 + 5, 46 (33%) 4 + 4, and 18 (13%) 5 + 3 disease. Invasive cribriform and/or intraductal carcinoma (n = 87, 62%) was observed more frequently in Gleason score 4 + 4 (93%) than 3 + 5 (47%; P < 0.001) and 5 + 3 (44%; P < 0.001) patients. Gleason pattern 5 was present in 110 (79%) men: as single cells and/or cords in 99 (90%) and solid fields in 32 (29%) cases. Solid field pattern 5 coexisted with cribriform architecture (23/32, 72%) more frequently than nonsolid pattern 5 cases (36/78, 46%, P = 0.02). In multivariable analysis including age, prostate-specific antigen, pT-stage, surgical margin status, and lymph node metastases, presence of cribriform architecture was an independent parameter for biochemical recurrence-free (hazard ratio (HR) 2.0, 95% confidence interval (CI) 1.0–3.7; P = 0.04) and metastasis-free (HR 3.5, 95% CI 1.0–12.3; P = 0.05) survival. In conclusion, invasive cribriform and/or intraductal carcinoma occurs more frequently in Gleason score 4 + 4 prostate cancer patients than in Gleason score 3 + 5 and 5 + 3, and is an independent parameter for biochemical recurrence and metastasis. Therefore, cribriform architecture has added value in risk stratification of Gleason score 8 prostate cancer patients.

BackgroundSurgically 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).ResultsTruncated homotypic P0 protein-based peptide sequences were C-terminally functionalized with the far-red cyanine dye Cy5. The lead compound Cy5-P0101–125 was selected after initial solubility, (photo)physical and in vitro evaluation (including P0-blocking experiments). Cy5-P0101–125 (KD = 105 ± 17 nM) allowed in vitro and ex vivo P0-related staining. Furthermore, Cy5-P0101–125 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 [111In]In-DTPA-P0101–125 does not enter the central nervous system (CNS).ConclusionP0101–125 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.

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 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.

Introduction The needs of cancer patients and survivors regarding discussing sexuality are frequently unmet, with many not receiving adequate information. To optimize information about sexuality and cancer, patients’ perspective is needed. The goals of this study were to investigate what kind of information Dutch cancer patients need, their ideas on how to improve communication, and to identify patients who are more in need of information regarding sexuality. Methods The Dutch Federation of Cancer Patient Organizations developed and conducted a nationwide 28-item online survey. The survey was distributed among cancer patients and survivors. Results In total, 2657 (ex) cancer patients participated, with a median age of 61 years, and half were male (45.2%). Of the respondents, 65% were in need of information about sexuality. Patients ≤ 61 years ( p  < 0.001), patients with a self-reported negative effect of cancer on sexuality (p < 0.001) and patients who were diagnosed less than 2 years ago ( p  < 0.04) reported a higher need for information. Regardless of type of cancer, patients were most in need of practical tips and practical information regarding sexuality. To enhance communication about sexuality, 64% of the respondents suggested that it would be of help if care providers give information as standard care. Conclusions (Ex) cancer patient prefer to receive standard information about sexuality by their care providers. According to patients’ preferences, information must include practical tips. Age, self-reported negative effect on sexuality status and time from diagnoses influenced the need for information.

Sexual abuse has been linked to strong effects on gastrointestinal health. Colonoscopy can provoke intense emotional reactions in patients with a sexual abuse history and may lead to avoidance of endoscopic procedures. To determine whether care around colonoscopy needs adjustment for patients with sexual abuse experience, thereby exploring targets for the improvement of care around colonoscopic procedures. Questionnaires were mailed to patients (n = 1419) from two centers within 11 months after colonoscopy. Differences in experience of the colonoscopy between patients with and without a sexual abuse history were assessed and patients' views regarding physicians' inquiry about sexual abuse and care around endoscopic procedures were obtained. A total of 768 questionnaires were analyzed. The prevalence of sexual abuse was 3.9% in male and 9.5% in female patients. Patients born in a non-western country reported more sexual abuse (14.9%) than those born in a western country (6.3%; p = 0.008). Discomfort during colonoscopy was indicated on a scale from 0 to 10, mean distress score of patients with sexual abuse was 4.8(± 3.47) compared to 3.5(± 3.11) in patients without a sexual abuse history (p = 0.007). Abdominal pain was a predictor for higher distress during colonoscopy (β = -0.019 (SE = 0.008); p = 0.02, as well as the number of complaints indicated as reason for colonoscopy (β = 0.738 (SE = 0.276); p = 0.008). Of patients with sexual abuse experience, 53.8% believed gastroenterologists should ask about it, 43.4% said deeper sedation during colonoscopy would diminish the distress. Sexual abuse is prevalent in patients presenting for colonoscopy. Patients with a sexual abuse history experience more distress during the procedure and indicate that extra attention around and during colonoscopy may diminish this distress.

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 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 μV; 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. Trial registration The trial is registered at the Dutch Trial registry (NTR7581)  https://trialsearch.who.int

Percentage Gleason pattern 4, invasive cribriform and/or intraductal carcinoma (IC/IDC) and minor pattern 5 are recognized as independent parameters for prostate cancer outcome, but are not incorporated in current grade groups (GGs). Two proof-of-principle studies have proposed alternative grading schemes based on percentage Gleason pattern 4/5 (integrated quantitative Gleason score; IQ-Gleason) and IC/IDC presence (cribriform grade; cGrade). Our objective was to compare the performance of GG, IQ-Gleason and cGrade for predicting biochemical recurrence and metastasis after radical prostatectomy (RP). RP specimens of 1064 patients were pathologically reviewed and graded according to the three schemes. Discriminative power for prediction of biochemical recurrence-free (BCRFS) and metastasis-free (MFS) survival was compared using Harrell’s c-index. The GG distribution at RP was 207 (19.4%) GG1, 472 (44.4%) GG2, 126 (11.8%) GG3, 140 (13.2%) GG4 and 119 (11.2%) GG5. Grading according to 5-tier IQ-Gleason and cGrade systems led to categorical shifts in 49.8% and 29.7% of cases, respectively. Continuous IQ-Gleason had the best performance for predicting BCRFS (c-index 0.743, 95% confidence interval (CI) 0.715–0.771), followed by cGrade (c-index 0.738, 95%CI 0.712–0.759), 5-tier categorical IQ-Gleason (c-index 0.723, 95%CI 0.695–0.750) and GG (c-index 0.718, 95%CI 0.691–0.744). Continuous IQ-Gleason (c-index 0.834, 95%CI 0.802–0.863) and cGrade (c-index 0.834, 95%CI 0.808–0.866) both had better predictive value for MFS than categorical IQ-Gleason (c-index 0.823, 95%CI 0.788–0.857) and GG (c-index 0.806, 95%CI 0.777–0.839). In conclusion, the performance of prostate cancer grading can be improved by alternative grading schemes incorporating percent Gleason pattern 4/5 and IC/IDC.