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Owing to the improvements in detection, diagnostics, and treatment, many men currently diagnosed with prostate cancer (PCa) have a low risk of PCa death. For many men PCa has become a chronic disease with a small risk of progression that remains even decades after date of diag-nosis. In this thesis PCa was used as an example of a chronic disease, since it holds all the main characteristics required by the WHO definition of a chronic disease. Against this background, the aim of this PhD thesis was to create models that can be used to quantify the probability of dif-ferent treatment trajectories and to assess the duration of certain disease states, while accounting for patient characteristics, disease severity, and primary treatment. In Paper I a state transition model was developed for prediction of dis-ease trajectories. The developed state transition model showed good consistency with a follow-up spanning up to 30 years. In Paper II a state transition model was developed and validated using age, Charlson comorbidity index, and a drug comorbidity index (DCI) based on filled drug prescriptions collected at a population-based level to estimate life expectancy. In Paper III the state transition model proposed in Paper I was used to assess 30-year PCa trajectories in men managed with active surveillance, in order to identify the ideal candidates for this management strategy. In Paper IV the state transition model from Paper I was updated includ-ing the castration resistant PCa (CRPC) state as an additional state and estimating the duration of the CRPC state as well as its outcomes. In Paper V, the updated state transition model from Paper IV was used to model long term outcomes for men with PCa managed with watchful waiting (WW). Since WW is currently recommended for men with PCa and life expectancy less than 10 years, the state transition model from Paper II was used to estimate life expectancy.

INTRODUCTION: The area of paediatric endourology is unique and is recognised to be challenging, and it requires a certain level of focused training and expertise. Our aim was to conduct a worldwide survey in order to gain an overview regarding the current practice patterns for minimally invasive treatments of paediatric upper urinary tract stone patients. MATERIAL AND METHODS: The survey was distributed between December 2021 and April 2022 through urology sections and societies in United Kingdom, Latin America and Asia. The survey was made up of 20 questions and it was distributed online using the free online Google Forms (TM). RESULTS: 221 urologists answered the survey with 56 responses each from India, South America and UK and 53 responses from the rest of Europe (15 countries). In total, 163 responders (73.7%) managed paediatric stone patients in their daily practice. Of the responders, 60.2% were adult urologists and 39.8% were paediatric urologists. 12.9% adult urologists and 20.4% paediatric urologists run independent clinics while some run combined adult and paediatric clinics sometimes with the support of the nephrologists. Only 33.9% urologists offered all surgical treatments [extracorporeal shock wave lithotripsy (ESWL), percutaneous nephrolithotomy (PCNL), ureteroscopy (URS) and retrograde intrarenal surgery (RIRS)]. CONCLUSIONS: Treatment of paediatric stones can vary according to country and legislations. Based on the results of this survey, minimally invasive methods such as URS and mini PCNL seem to have become more popular. In most institutions a collaboration exists between adult and paediatric urologists, which is the key for a tailored decision making, counselling and treatment success.

BACKGROUND The novel pulsed thulium:yttrium-aluminum-garnet (p-Tm:YAG) laser was recently introduced. Current studies present promising p-Tm:YAG ablation efficiency, although all are based on non-human stone models or with unknown stone composition. The present study aimed to evaluate p-Tm:YAG ablation efficiency for stone dust from human urinary stones of known compositions. METHODS Calcium oxalate monohydrate (COM) and uric acid (UA) stones were subjected to lithotripsy in vitro using a p-Tm:YAG laser generator (Thulio®, Dornier MedTech GmbH, Germany). 200 J was applied at 0.1 J × 100 Hz, 0.4 J × 25 Hz or 2.0 J × 5 Hz (average 10W). Ablated stone dust mass was calculated from weight difference between pre-lithotripsy stone and post-lithotripsy fragments > 250 µm. Estimated ablated volume was calculated using prior known stone densities (COM: 2.04 mg/mm$^{3}$, UA: 1.55 mg/mm$^{3}$). RESULTS Mean ablation mass efficiency was 0.04, 0.06, 0.07 mg/J (COM) and 0.04, 0.05, 0.06 mg/J (UA) for each laser setting, respectively. This translated to 0.021, 0.029, 0.034 mm$^{3}$/J (COM) and 0.026, 0.030, 0.039 mm$^{3}$/J (UA). Mean energy consumption was 26, 18, 17 J/mg (COM) and 32, 23, 17 J/mg (UA). This translated to 53, 37, 34 J/mm$^{3}$ (COM) and 50, 36, 26 J/mm$^{3}$ (UA). There were no statistically significant differences for laser settings or stone types (all p > 0.05). CONCLUSION To our knowledge, this is the first study showing ablation efficiency of the p-Tm:YAG laser for stone dust from human urinary stones of known compositions. The p-Tm:YAG seems to ablate COM and UA equally well, with no statistically significant differences between differing laser settings.

Context Laser performance for lithotripsy is currently reported using units of measurement such as J/mm3, mm3/J, mm3/s, s/mm3, and mm3/min. However, there are no current standardized definitions or terminology for these metrics. This may lead to confusion when assessing and comparing different laser systems. Objective The primary objective was to summarize outcome values and corresponding terminology from studies on laser lithotripsy performance using stone volume in relation to time or energy. The secondary objective was to propose a standardized terminology for reporting laser performance metrics. Evidence acquisition A systematic review of the literature was conducted using the search string (“j*/mm3” OR “mm3/j*” OR “mm3/s*” OR “s*/mm3” OR “mm3/min*” OR “min*/mm3” AND “lithotripsy”) on Scopus, Web of Science, Embase, and PubMed databases. Study selection, data extraction, and quality assessment were performed independently by two authors. Evidence synthesis A total of 28 studies were included, covering holmium:yttrium-aluminum-garnet (Ho:YAG), MOSES, and thulium fiber laser (TFL) technologies. Laser energy consumption values reported for the studies ranged from 2.0 – 43.5 J/mm3 in vitro and from 2.7 – 47.8 J/mm3 in vivo, translating to laser ablation efficiency of 0.023 – 0.500 mm3/J and 0.021 – 0.370 mm3/J, respectively. Laser ablation speeds ranged from 0.3 – 8.5 mm3/s in vivo, translating to lasing time consumption of 0.12 – 3.33 s/mm3. Laser efficacy ranged from 4.35 – 51.7 mm3/min in vivo. There was high heterogeneity for the terminology used to describe laser performance for the same metrics. Conclusions The range of laser performance metric values relating stone volume to energy or time is wide, with corresponding differing terminology. We propose a standardized terminology for future studies on laser lithotripsy, including laser ablation efficiency (mm3/J), laser ablation speed (mm3/s), and laser energy consumption (J/mm3). Laser efficacy (mm3/min) is pro

Flexible ureteroscopy (fURS) with laser lithotripsy is currently the gold standard surgical treatment for ureteral and kidney stones with a maximum diameter of 2 cm [...].

PURPOSE To evaluate whether stone dust can be obtained from all prevailing stone composition types using the novel pulsed thulium:YAG (p-Tm:YAG), including analysis of stone particle size after lithotripsy. METHODS Human urinary stones of 7 different compositions were subjected to in vitro lithotripsy using a p-Tm:YAG laser with 270 µm silica core fibers (Thulio$^{®}$, Dornier MedTech GmbH$^{®}$, Wessling, Germany). A cumulative energy of 1000 J was applied to each stone using one of three laser settings: 0.1 J × 100 Hz, 0.4 J × 25 Hz and 2.0 J × 5 Hz (average power 10 W). After lithotripsy, larger remnant fragments were separated from stone dust using a previously described method depending on the floating ability of dust particles. Fragments and dust samples were then passed through laboratory sieves to evaluate stone particle count according to a semiquantitative analysis relying on a previous definition of stone dust (i.e., stone particles ≤ 250 µm). RESULTS The p-Tm:YAG laser was able to produce stone dust from lithotripsy up to measured smallest mesh size of 63 µm in all seven stone composition types. Notably, all dust samples from all seven stone types and with all three laser settings had high counts of particles in the size range agreeing with the definition stone dust, i.e., ≤ 250 µm. CONCLUSION This is the first study in the literature proving the p-Tm:YAG laser capable of dusting all prevailing human urinary stone compositions, with production of dust particles ≤ 250 µm. These findings are pivotal for the broader future implementation of the p-Tm:YAG in clinical routine.

OBJECTIVE The objective of this study was to evaluate a new concept in flexible ureteroscopy: instrumental dead space (IDS). For this purpose, various proximal working channel connector designs, as well as the impact of ancillary devices occupying the working channel were evaluated in currently available flexible ureteroscopes. DESIGN AND METHODS IDS was defined as the volume of saline irrigation needed to inject at the proximal connector for delivery at the distal working channel tip. Because IDS is related to working channel diameter and length, proximal connector design, as well as occupation of working channel by ancillary devices, these parameters were also reviewed. RESULTS IDS significantly varied between flexible ureteroscope models, ranging from 1.1 ml for the Pusen bare scopes, to 2.3 ml for Olympus scopes with their 4-way connector (p < 0.001). Proximal connector designs showed a high degree of variability in the number of available Luer locks, valves, seals, angles, and rotative characteristics. The measured length of the working channel of bare scopes ranged between 739 and 854 mm and significantly correlated with measured IDS (R$^{2}$ = 0.82, p < 0.001). The coupling of scopes with an alternative ancillary proximal connector and the insertion of ancillary devices into the working channel significantly reduced IDS (mean IDS reduction of 0.1 to 0.5 ml; p < 0.001). CONCLUSIONS IDS appears as a new parameter that should be considered for future applications of flexible ureteroscopes. A low IDS seems desirable for several clinical applications. The main factors impacting IDS are working channel and proximal connector design, as well as ancillary devices inserted into the working channel. Future studies should clarify how reducing IDS may affect irrigation flow, intrarenal pressure, and direct in-scope suction, as well as evaluate the most desirable proximal connector design properties.