Consultation on UTUC II Stockholm 2022: diagnostic and prognostic methods-what's around the corner?

PURPOSE: To map current literature and provide an overview of upcoming future diagnostic and prognostic methods for upper tract urothelial carcinoma (UTUC), including translational medical science. METHODS: A scoping review approach was applied to search the literature. Based on the published literature, and the experts own experience and opinions consensus was reached through discussions at the meeting Consultation on UTUC II in Stockholm, September 2022. RESULTS: The gene mutational profile of UTUC correlates with stage, grade, prognosis, and response to different therapeutic strategies. Analysis of pathway proteins downstream of known pathogenic mutations might be an alternative approach. Liquid biopsies of cell-free DNA may detect UTUC with a higher sensitivity and specificity than urinary cytology. Extracellular vesicles from tumour cells can be detected in urine and may be used to identify the location of the urothelial carcinoma in the urinary tract. 3D microscopy of UTUC samples may add information in the analysis of tumour stage. Chemokines and chemokine receptors were linked to overall survival and responsiveness to neoadjuvant chemotherapy in muscle-invasive bladder cancer, which is potentially also of interest in UTUC. CONCLUSION: Current diagnostic methods for UTUC have shortcomings, especially concerning prognostication, which is important for personalized treatment decisions. There are several upcoming methods that may be of interest for UTUC. Most have been studied for urothelial carcinoma of the bladder, and it is important to keep in mind that UTUC is a different entity and not all methods are adaptable or applicable to UTUC.

Consultation on UTUC II Stockholm 2022: diagnostics, prognostication, and follow-up-where are we today?

PURPOSE: To summarise the current knowledge regarding diagnostics, prognostication and follow-up in upper tract urothelial carcinoma (UTUC). METHODS: A scoping review combined with expert opinion was applied to provide an overview of the current research field. Based on the published literature and the experts' own experience and opinions, consensus was reached through presentations and discussions at the meeting Consultation on UTUC II in Stockholm 2022. RESULTS: The strongest prognostic factors in UTUC are tumour grade and stage. They are correlated, and grade is used for indirect staging. The diagnostic examinations should include multiphase computed tomography urography (CTU) with corticomedullary phase, and urethrocystoscopy with cytology. If there is no clear diagnosis for clinical decision-making, ureterorenoscopy (URS) with focal cytology and biopsies should be performed. Both WHO classification systems (1973/1999 and 2004/2016) should be used. Novel biomarker tests are not yet widespread nor recommended for the detection of UTUC. Long-term, regular follow-up, including URS in patients who have had organ-sparing treatment, is important to check for tumour recurrences, intravesical recurrences, metastases and progression of the tumour. CONCLUSION: Proper diagnostics with correct grading of UTUC are necessary for appropriate treatment decisions. The diagnostics should include CTU with corticomedullary phase, urine or bladder cytology, URS with focal barbotage cytology, and biopsies when needed for proper diagnosis and risk stratification. Regular, long-term follow-ups are fundamental, due to the high rate of recurrence and risk of progression.

Identification of early stage and metastatic prostate cancer using electrochemical detection of beta-2-microglobulin in urine samples from patients.

To improve prostate cancer (PCa) diagnosis, it is imperative to identify novel biomarkers and establish effective screening techniques. Here, we introduce electrochemical biosensing of ß-2-Microglobulin (ß2M) in urine as a potential diagnostic tool for PCa. The immunosensor is composed of a screen-printed graphene electrode coated with anti ß2M antibodies. The sensor is capable of detecting the protein directly in urine without any sample pretreatment within 45 min including sample incubation and a lower limit of detection of 204 µg/L. The sensor demonstrated a significant difference in the ß2M-creatinine ratio in urine between control and both local- and metastatic PCa (mPCa) (P = 0.0302 and P = 0.0078 respectively), and between local- and mPCa (P = 0.0302). This first example of electrochemical sensing of ß2M for the diagnosis of PCa may set the stage for an affordable, on-site screening technique for PCa.

Kidney stone disease.

Kidney stone disease is rapidly increasing with a strong relationship to metabolic syndrome. This review gives a brief overview of the current state and current treatment modalities. Increasing use of CT and ultrasound scans leads to increased diagnosis of asymptomatic kidney stones, which rarely require treatment. The trend in stone treatment goes towards endoscopic lithotripsy which together with ESWL enables a personalised approach. Obstructive stones with infection require urgent intervention to reduce mortality. Increased fluid intake, dietary changes as well as potassium citrate supplements are the most important elements in stone prevention in the common idiopathic stone disease.

Gadolinium-enhanced MRI visualizing backflow at increasing intra-renal pressure in a porcine model.

INTRODUCTION: Intrarenal backflow (IRB) is known to occur at increased intrarenal pressure (IRP). Irrigation during ureteroscopy increases IRP. Complications such as sepsis is more frequent after prolonged high-pressure ureteroscopy. We evaluated a new method to document and visualize intrarenal backflow as a function of IRP and time in a pig model. METHODS: Studies were performed on five female pigs. A ureteral catheter was placed in the renal pelvis and connected to a Gadolinium/ saline solution 3 ml/L for irrigation. An occlusion balloon-catheter was left inflated at the uretero-pelvic junction and connected to a pressure monitor. Irrigation was successively regulated to maintain steady IRP levels at 10, 20, 30, 40 and 50 mmHg. MRI of the kidneys was performed at 5-minute intervals. PCR and immunoassay analyses were executed on the harvested kidneys to detect potential changes in inflammatory markers. RESULTS: MRI showed backflow of Gadolinium into the kidney cortex in all cases. The mean time to first visual damage was 15 minutes and the mean registered pressure at first visual damage was 21 mmHg. On the final MRI the mean percentage of IRB affected kidney was 66% after irrigation with a mean maximum pressure of 43 mmHg for a mean duration of 70 minutes. Immunoassay analyses showed increased MCP-1 mRNA expression in the treated kidneys compared to contralateral control kidneys. CONCLUSIONS: Gadolinium enhanced MRI provided detailed information about IRB that has not previously been documented. IRB occurs at even very low pressures, and these findings are in conflict with the general consensus that keeping IRP below 30-35 mmHg eliminates the risk of post-operative infection and sepsis. Moreover, the level of IRB was documented to be a function of both IRP and time. The results of this study emphasize the importance of keeping IRP and OR time low during ureteroscopy.

Bladder diverticulum in Ehlers-Danlos syndrome.

Ehlers-Danlos syndrome (EDS) is a group of hereditary connective tissue disorders which are clinically characterized by hypermobility of joints, hyperelasticity of skin and tissue insufficiency, sometimes leading to herniation, bleeding, and organ rupture. This is a case report of a 55-year-old man with EDS and a big bladder diverticulum in which we discuss treatment strategy in patients with EDS and bladder diverticula. Initially, treatment approach should be conservative due to high recurrence rates and potential complications following surgical procedures. Invasive procedures - preferably minimally invasive - may be indicated, based on an individual risk evaluation.

An Intervention Offering Self-management Support Through mHealth and Health Coaching to Patients With Prostate Cancer: Interpretive Description of Patients' Experiences and Perspectives.

BACKGROUND: Observational management strategies such as active surveillance and watchful waiting are considered to be acceptable approaches in patients with low-risk localized prostate cancer and a safe alternative to aggressive treatment. During observational management, treatment is postponed until the disease progresses, which often never occurs. However, approximately 90% of patients with a low-risk disease choose aggressive treatment owing to anxiety. Strategies to address anxiety are needed for optimal management of this population and to improve the quality of life of patients with low-risk localized prostate cancer. A review highlighted that mobile health (mHealth) in tandem with health coaching can support patients' self-management of health behaviors and improve well-being. OBJECTIVE: This study aims to explore patients' experiences with and perspectives on an intervention offering self-management support through the use of mHealth devices and health coaching to identify supportive features that enable patients to perform sustainable changes that improve well-being. METHODS: We used an interpretive description approach, combining semistructured interviews with 13 purposively selected patients with prostate cancer and participant observations of patient-coach interactions in coaching sessions. The interviews were transcribed and analyzed. The self-determination theory was used as a theoretical lens. Field notes and coaching notes from each session were used to orient data generation and confirm or challenge the analysis. RESULTS: Our analysis suggested that patients' self-awareness and psychological identity influenced their experiences with and perspectives on the self-management support offered by mHealth and health coaching in clinical practice. The patients' individual experiences and perspectives indicated that they placed themselves in a dynamic continuum of sustaining or repressing their identity, self-awareness, and individual qualities. Our analysis revealed 4 interacting themes, all related to the psychological identity of the patients. CONCLUSIONS: For the group of patients with prostate cancer to experience well-being, we found it important for them to sustain their self-image when offered a self-management intervention. Motivation and autonomy were important aspects for the individual patients to sustain their self-image throughout the intervention. In contrast, demotivation and a sense of paternalism could result in fostering an experience of having to repress self-awareness.

The Danish linguistic validation of the Ureteral Stent Symptoms Questionnaire.

INTRODUCTION: The aim of the study was to validate the Ureteral Stent Symptom Questionnaire (USSQ) in Danish for patients with indwelling ureteral stents. METHODS: The linguistic validation of the original USSQ was performed following standardised multi-step translation procedures. Seventy patients with indwelling ureteral stents were asked to complete the Danish USSQ one and two weeks after stent placement and four weeks after stent removal. RESULTS: A total of 65 patients (92.9%) completed the USSQ. Statistical evaluation revealed good internal consistency in all domains except work performance. Satisfactory convergent validity (less-than -0.4 or greater-than 0.4) was demonstrated for urinary symptoms, body pain and global quality of life. The test-retest reliability-coefficient was statistically significant for urinary symptoms, general health, pain and sexual matters. Inter-domain associations were positive and monotone for all subscales. All sub-scores, except sexual matters, significantly decreased from one week after stent insertion to four weeks after stent removal (p less-than 0.001). CONCLUSION: The Danish USSQ is a reliable and valid instrument with which to evaluate urinary symptoms and general health in patients with indwelling ureteral stents. FUNDING: Ideforum, Vejle Hospital, University Hospital of Southern Denmark, granted 80,000 DKK to support this work. TRIAL REGISTRATION: The Danish National Ethics Committee and Region Syddanmark approved the study (Study approval number 20192000-168 and journal number 19-52219, respectively).

Correlation between stage of prostate cancer and tyrosine and tryptophan in urine samples measured electrochemically.

Prostate cancer (PCa) is the second most common cancer in men and one of the leading causes of cancer-related deaths. Early detection is the key to successful treatment and provides the greatest chance to cure the patient. Currently, early detection involves screening for prostate-specific antigen levels in blood, which is not a tumor-specific biomarker. There is a critical need to develop clinically useful methods for screening for more reliable biomarkers. Here, we introduce an electrochemical biosensor that measures the concentrations of the amino acids tyrosine and tryptophan, and propose it as a possible diagnostic and prognostic tool for PCa. The limits of detection of tyrosine and tryptophan using the electrochemical sensors were 1.15 and 1.13 µmol/L in 1:10 urine: PBS, respectively. This study is the first to present electrochemical measurements of tyrosine and tryptophan directly in patient urine samples. We demonstrated an inverse correlation between the measured electrochemical signals and the severity of PCa. The most notable observation was a significant difference between controls and metastatic PCa patients (P ≤ 0.001). This observation was further validated using Liquid-Chromatography-Mass Spectrometry. Our data provides the basis for further research with electrochemical measurements of tyrosine and tryptophan as potential biomarkers for PCa.

Healthcare Professionals' Experiences and Perspectives of Facilitating Self-Management Support for Patients with Low-Risk Localized Prostate Cancer via mHealth and Health Coaching.

Introduction: Self-monitoring of self-management interventions with the use of mobile health (mHealth) can enhance patients' well-being. Research indicates that mHealth and health coaching act symbiotically to providing a more constructive outcome. Nurse coaches seem to have a significant role in translating the patients' tracked data. Objective: The objective was to explore healthcare professionals' experiences of an intervention offering self-management support through mHealth and health coaching for patients with prostate cancer. Methods: We used the interpretive description methodology, combining semi-structured individual and focus group interviews and participant observations of patient-coach interactions and use of mHealth in coaching sessions. The study was conducted between June 2017 and August 2020. Results: The nurse coaches experienced motivation and autonomy when possessing the right competences for coaching. Furthermore, the nurse coaches experienced conflicting expectations of their roles when having to integrate mHealth. Conclusion: The experience of being competent, autonomous, and confident is important for the nurse coaches to be mentally present during the coaching sessions. On the other hand, the findings indicate that having the sense of not being confident in one's own ability to perform leads to reduced motivation.

Shorter anogenital distance is observed in patients with testicular microlithiasis using magnetic resonance imaging.

OBJECTIVE: To investigate the anogenital distance in patients with and without testicular microlithiasis (TML). METHODS: A total of 101 patients underwent a conventional standard clinical B-mode scrotal ultrasonography and scrotal MRI. The patients were divided into two groups: patients with TML and non-TML. The latter served as control group. The anogenital distance was measured by a straight line from center of the anus to the posterior base of scrotum using MRI. RESULTS: In the TML group, mean AGD was 5.4 (± 1.07) cm (range 29-79 mm), and in non-TML 5.9 (± 1.03) cm (range 35-85 mm) (p = 0.04). CONCLUSION: MRI is a useful tool to measure the AGD. It is easy to perform without any discomfort to patients. We found AGD to be lower in patients with TML.

The Balance of Patient Involvement: Patients' and Health Professionals' Perspectives on Decision-Making in the Treatment of Advanced Prostate Cancer.

Research has shown that involving patients in decisions on treatment may have positive effects for patients. However, there are different understandings of what involving patients implies and different attitudes among physicians toward sharing decisions with patients. This study aimed to explore the attitude of patients with advanced prostate cancer to involvement in treatment decisions and physicians' and nurses' approach to patient involvement. Moreover, it aimed to explore whether the decision-making changes as the treatment course progresses. Data were collected through participant observations and interviews. It was found that treatment decisions are primarily considered as part of physicians' role. Physicians' attitudes to patient involvement in treatment decisions depended on the type of treatment. Among patients and health professionals, there was a lack of confidence in the ability of patients to participate in the decisions. Health professionals and patients have different attitudes toward patient involvement and different views on what it entails.

The utility of automated volume analysis of renal stones before and after shockwave lithotripsy treatment.

This study aimed to evaluate the additional utility of an automated method of estimating volume for stones being treated with shockwave lithotripsy (SWL) using computed tomography (CT) images compared to manual measurement. Utility was assessed as the ability to accurately measure stone burden before and after SWL treatment, and whether stone volume is a better predictor of SWL outcome than stone diameter. 72 patients treated with SWL for a renal stone with available CT scans before and after treatment were included. Stone axes measurement and volume estimation using ellipsoid equations were compared to volume estimation using software using CT textural analysis (CTTA) of stone images. There was strong correlation (r > 0.8) between manual and CTTA estimated stone volume. CTTA measured stone volume showed the highest predictive value (r2 = 0.217) for successful SWL outcome on binary logistic regression analysis. Three cases that were originally classified as 'stone-free with clinically insignificant residual fragments' based on manual axis measurements actually had a larger stone volume based on CTTA estimation than the smallest fragments remaining for cases with an outcome of 'not stone-free'. This study suggests objective measurement of total stone volume could improve estimation of stone burden before and after treatment. Current definitions of stone-free status based on manual measurements of residual fragment sizes are not accurate and may underestimate remaining stone burden after treatment. Future studies reporting on the efficacy of different stone treatments should consider using objective stone volume measurements based on CT image analysis as an outcome measure of stone-free state.

Combining mHealth and health-coaching for improving self-management in chronic care. A scoping review.

BACKGROUND: Self-management approaches are widely used to improve chronic care. In this context, health care professionals call for efficient tools to engage patients in managing their illness. Mobile health (mHealth), defined by WHO as medical and public health practice supported by mobile devices, is demonstrated to enhance self-management and health-coaching as an engaging tool in supporting behaviour change. Nevertheless, it is unclear how health-coaching and mHealth can benefit from each other. OBJECTIVE: We conducted a scoping review to provide a literature-overview and identify any existing gaps in knowledge of mHealth in combination with health-coaching interventions for improving self-management in patients with chronic diseases. PATIENT INVOLVEMENT: No patients were involved in the review process. METHODS: The five-stage framework by Arksey and O'Malley was used. The review surveys; PubMed, CINAHL, Embase, Scopus, and PsycInfo. Two independent reviewers performed review selection and characterization. RESULTS: The review points at two approaches; (i) coaching used to support mHealth and (ii) mHealth as support for coaching. The findings suggest that patients prefer physical interactions to telecommunication. mHealth was primarily used to facilitate telecommunication and to monitor disease aspects. DISCUSSION: We found that mHealth and health-coaching interventions benefit from each other. The review report on a considerable unclarity in the coaching-methods and that the patients were more satisfied with physical interactions than mHealth. We suggest to prioritize human contact and to explore more personalized health technology. PRACTICAL VALUE: This scoping review can provide a framework for researchers and care providers to support discussion and introduction of new approaches and technology in self-management for patients with chronic diseases, thereby improving patients' quality of life.

Consultation on kidney stones, Copenhagen 2019: aspects of intracorporeal lithotripsy in flexible ureterorenoscopy.

PURPOSE: To summarize current knowledge on intracorporeal laser lithotripsy in flexible ureterorenoscopy (fURS), regarding basics of laser lithotripsy, technical aspects, stone clearance, lithotripsy strategies, laser technologies, endoscopes, and safety. METHODS: A scoping review approach was applied to search literature in PubMed, EMBASE, and Web of Science. Consensus was reached through discussions at the Consultation on Kidney Stones held in September 2019 in Copenhagen, Denmark. RESULTS AND CONCLUSIONS: Lasers are widely used for lithotripsy during fURS. The Holmium laser is still the predominant technology, and specific settings for dusting and fragmenting have evolved, which has expanded the role of fURS in stone management. Pulse modulation can increase stone ablation efficacy, possibly by minimizing stone retropulsion. Thulium fibre laser was recently introduced, and this technology may improve laser lithotripsy efficiency. Small fibres give better irrigation, accessibility, and efficiency. To achieve optimal results, laser settings should be adjusted for the individual stone. There is no consensus whether the fragmentation and basketing strategy is preferable to the dusting strategy for increasing stone-free rate. On the contrary, different stone scenarios call for different lithotripsy approaches. Furthermore, for large stone burdens, all laser settings and lithotripsy strategies must be applied to achieve optimal results. Technology for removing dust from the kidney should be in focus in future research and development. Safety concerns about fURS laser lithotripsy include high intrarenal pressures and temperatures, and measures to reduce both those aspects must be taken to avoid complications. Technology to control these parameters should be targeted in further studies.

No time for reflection: Patient experiences with treatment-related decision-making in advanced prostate cancer.

BACKGROUND: The rationale of the study was the predominant understanding that patient involvement in treatment-related decision-making is essential and that communication with cancer patients can affect their quality of life, satisfaction with care, and psychosocial and medical outcomes positively. AIM: This study explored how patients with advanced prostate cancer experience the communication with health professionals and their experiences of how and by whom treatment-related decisions were made. METHODS: A phenomenological-hermeneutic research design was applied, and data were collected using qualitative interviews supplemented with participant observations in a urological outpatient clinic at a regional hospital in Denmark. Thirteen patients participated. Data were analysed using Ricoeur's theory of interpretation. FINDINGS: The patients experienced the course as being routine and that decisions related to treatment were made in advance. Three themes were identified: (1) Fast track diagnosing and treatment, (2) Off course I should have this treatment, and (3) They don't ask about existential issues. CONCLUSION: The study concluded that patients experienced communication primarily revolved around disease- and treatment-related issues and that it was characterised as efficient and straightforward, but insufficient. The patients experienced that the doctors made treatment-related decisions without involving them.

Association between risk factors and testicular microlithiasis.

BACKGROUND: Testicular microlithiasis and its clinical significance are not fully understood. Testicular microlithiasis and risk factors have been associated with testicular cancer. The role of testicular microlithiasis is investigated. PURPOSE: To investigate the association between testicular microlithiasis and socioeconomic and other pre-diagnostic factors. MATERIAL AND METHODS: All men who had a scrotal ultrasound examination at the Department of Radiology, Vejle Hospital, during 2001-2013 were included. They were categorized as patients with and without testicular microlithiasis and compared with pre-diagnostic data from a nationwide registry. A total of 2404 men (283 [11.8%] with testicular microlithiasis and 2121 [88.2%] without testicular microlithiasis) were included. The association between testicular microlithiasis and pre-diagnostic conditions was investigated with logistic regression. RESULTS: Overall, we found no statistically significant differences in demographics, socioeconomic characteristics, or testicular diseases in men with and without testicular microlithiasis. Men with testicular microlithiasis had more often been treated for infertility (odds ratio [OR] 2.09, 95% confidence interval [CI] 0.84-5.24) and testicular torsion (OR 1.58, 95% CI 0.34-7.36) compared to men without testicular microlithiasis. We found no association between sexually transmitted diseases and testicular microlithiasis. CONCLUSION: Treatment for infertility and torsion was non-significantly associated with testicular microlithiasis and no other association was found. These data do not suggest early exposure is related to testicular microlithiasis.

Consultation on UTUC, Stockholm 2018: aspects of treatment.

PURPOSE: To provide an overview of treatment modalities for management of upper tract urothelial carcinoma (UTUC). METHODS: In accordance with the standards for a scoping review, data presentation and discussion at the Consultation on UTUC in Stockholm, 6-7 September 2018, consensus was reached on the latest and most important treatment recommendations for UTUC. Using Pubmed, Web of Science, and Embase, publications were selected based on quality, clinical relevance, and level of evidence. RESULTS: Kidney-sparing surgery should be attempted for low-grade UTUC. Radical nephroureterectomy with bladder cuff excision is first option for high-grade disease. Post-operative bladder instillation of chemotherapy should be offered after RNU to reduce intravesical recurrence rate. Identification of tumor grade and stage is crucial when selecting treatment. Ureteroscopic management of low-grade and non-invasive UTUC achieves disease-free survival similar to that offered by radical nephroureterectomy but seems to be a risk factor for intravesical recurrence. Lymphadenectomy appears important for high-risk disease, although the therapeutic benefit needs further validation. There is little evidence supporting use of Bacillus Calmette-Guérin (BCG) and mitomycin C as monotherapy and adjuvant treatment in UTUC. A randomized clinical trial has indicated that platin-based chemotherapy for invasive UTUC improves disease-free survival, suggesting that adjuvant chemotherapy should be considered standard care for ≥ T2 N0-3M0 disease. CONCLUSIONS: Risk stratification assessment is feasible and mandatory in UTUC. Identification of tumor grade and stage is essential for optimal treatment selection. Kidney-sparing surgery should be offered in low-risk disease, whereas radical nephroureterectomy and adjuvant chemotherapy should be considered in high-risk disease.

Consultation on UTUC, Stockholm 2018 aspects of risk stratification: long-term results and follow-up.

PURPOSE: To summarize current knowledge on upper urinary tract carcinoma (UTUC) regarding risk stratification, long-term results, and follow-up. METHODS: A scoping review approach was applied to search literature in Pubmed, Web of Science, and Embase. Consensus was reached through discussions at Consultation on UTUC, September 2018, Stockholm. RESULTS: To optimize oncological outcome considering both cancer-specific survival (CSS) and overall survival (OS), it is essential to identify pre- and postoperative prognostic factors. In low-risk UTUC, kidney-sparing surgery (KSS) and radical nephroureterectomy (RNU) offer equivalent CSS, whereas RNU may result in poorer OS due to nephron loss. For more aggressive tumours, undergrading can lead to insufficient treatment. The strongest prognostic factors are tumour stage and grade. Determining grade is best achieved by ureterorenoscopy (URS) with focal samples, biopsy and cytology. Staging is more difficult but can be indirectly achieved by multiphase computed tomography urography (CTU) or tumour grade determined by cytology and histopathology. Patients treated with KSS should be monitored closely with regular follow-ups (URS and CTU). CONCLUSION: KSS should be offered in low-risk UTUC when feasible, whereas RNU is the treatment of choice in organ-confined high-risk UTUC. Intravesical recurrence (IVR) is common after RNU, but a single postoperative dose of mitomycin instillation decreases IVR. Endourological management has high local and bladder recurrence rates; however, its effect on CSS or overall survival OS is unclear. RNU is associated with significant risk of chronic kidney disease. Careful selection of patients and risk stratification are mandatory, and patients should be followed according to strict protocols.