An international delphi survey and consensus meeting to define the risk factors for ureteral stricture after endoscopic treatment for urolithiasis.

PURPOSE: Iatrogenic ureteral strictures (US) after endoscopic treatment for urolithiasis represent a significant healthcare concern. However, high-quality evidence on the risk factors associated with US is currently lacking. We aimed to develop a consensus statement addressing the definition, risk factors, and follow-up management of iatrogenic US after endoscopic treatment for urolithiasis. METHODS: Utilizing a modified Delphi method, a steering committee developed survey statements based on a systematic literature review. Then, a two-round online survey was submitted to 25 experts, offering voting options to assess agreement levels. A consensus panel meeting was held for unresolved statements. The predetermined consensus threshold was set at 70%. RESULTS: The steering committee formulated 73 statements. In the initial survey, consensus was reached on 56 (77%) statements. Following in-depth discussions and refinement of 17 (23%) statements in a consensus meeting, the second survey achieved consensus on 63 (86%) statements. This process underscored agreement on pivotal factors influencing US in endoscopic urolithiasis treatments. CONCLUSIONS: This study provides a comprehensive list of categorized risk factors for US following endoscopic urolithiasis treatments. The objectives include enhancing uniformity in research, minimizing redundancy in outcome assessments, and effectively addressing risk factors associated with US. These findings are crucial for designing future clinical trials and guiding endoscopic surgeons in mitigating the risk of US.

Ureteral stricture rate after endoscopic treatments for urolithiasis and related risk factors: systematic review and meta-analysis.

PURPOSE: We aimed to accurately determine ureteral stricture (US) rates following urolithiasis treatments and their related risk factors. METHODS: We conducted a systematic review and meta-analysis following the PRISMA guidelines using databases from inception to November 2023. Studies were deemed eligible for analysis if they included ≥ 18 years old patients with urinary lithiasis (Patients) who were subjected to endoscopic treatment (Intervention) with ureteroscopy (URS), percutaneous nephrolithotomy (PCNL), or shock wave lithotripsy (SWL) (Comparator) to assess the incidence of US (Outcome) in prospective and retrospective studies (Study design). RESULTS: A total of 43 studies were included. The pooled US rate was 1.3% post-SWL and 2.1% post-PCNL. The pooled rate of US post-URS was 1.9% but raised to 2.7% considering the last five years' studies and 4.9% if the stone was impacted. Moreover, the pooled US rate differed if follow-ups were under or over six months. Patients with proximal ureteral stone, preoperative hydronephrosis, intraoperative ureteral perforation, and impacted stones showed higher US risk post-endoscopic intervention with odds ratio of 1.6 (P = 0.05), 2.6 (P = 0.009), 7.1 (P < 0.001), and 7.47 (P = 0.003), respectively. CONCLUSIONS: The overall US rate ranges from 0.3 to 4.9%, with an increasing trend in the last few years. It is influenced by type of treatment, stone location and impaction, preoperative hydronephrosis and intraoperative perforation. Future standardized reporting and prospective and more extended follow-up studies might contribute to a better understanding of US risks related to calculi treatment.

Circulating miR-141 and miR-375 are associated with treatment outcome in metastatic castration resistant prostate cancer.

Metastatic castration resistant prostate cancer (mCRPC) is associated with high mortality, where monitoring of disease activity is still a major clinical challenge. The role of microRNAs (miRs) has been widely investigated in prostate cancer with both diagnostic and prognostic potential. The aim of this study was to investigate the relationship between circulating miRs and treatment outcome in mCRPC patients. The relative expression of five miRs (miR-93-5p, -125b-1-5p, -141-3p, -221-3p, and miR-375-3p) was investigated in plasma samples from 84 mCRPC patients; 40 patients were treated with docetaxel (DOC cohort) and 44 patients with abiraterone (ABI cohort). Blood was sampled at baseline before treatment start and at radiological progression. The plasma levels of four miRs; miR-93-5p, -141-3p, -221-3p, and miR-375-3p decreased significantly after treatment initiation in patients receiving docetaxel, and for miR-141-3p and miR-375-3p the level increased again at the time of radiological progression. In the patients treated with abiraterone, the plasma level of miR-221-3p likewise decreased significantly after the first treatment cycle. High baseline levels of both miR-141-3p and miR-375-3p were significantly associated with a shorter time to radiological progression in both cohorts. Additionally, high baseline levels of miR-141-3p and miR-221-3p were significantly associated with a shorter overall survival (OS) in the ABI cohort, while high levels of miR-141-3p and miR-375-3p were significantly associated with shorter OS in the DOC cohort. Plasma levels of miR-141-3p and miR-375-3p may predict time to progression in mCRPC patients treated with docetaxel or abiraterone. The clinical impact of these findings is dependent on validation in larger cohorts.

Characteristics of symptomatic men with testicular microlithiasis - A Danish cross-sectional questionnaire study.

Testicular microlithiasis (TML) is an incidental finding at ultrasonography of the scrotum. A link between testicular microlithiasis and testicular cancer has been suggested. However, the majority of studies are retrospective using ultrasonography with minor data on health status and life style characteristics. Our objective was to investigate if lifestyle and health are associated with TML. In 2014, we conducted a self-administered questionnaire survey including 1538 men, who all due to testicular/scrotal symptoms had an ultrasound investigation of the scrotum during 2004-2013. The men were divided into men with TML and men without. The 23-items questionnaire included items on age, height, weight, lifestyle (alcohol consumptions, smoking habits, workload, exercise and food), previous diseases in the testicles, pain and consumption of analgesics. The prevalence of TML was 12.8%. Overall, lifestyle factors did not vary between men with or without TML. However, men with TML did consume more crisp than men without. Development of TML was not associated to classic life style factors such as alcohol consumption, smoking habits, or mothers smoking during pregnancy. Also, age and height could not be linked to presence of TML. We did find, however, that men with TML experienced less physical activity and consumed more crisp than men without TML. Since ingestion of crisps has potential carcinogenic effect (acrylamide), this finding needs confirmation in a separate study.

Complications associated with ureterorenoscopy (URS) related to treatment of urolithiasis: the Clinical Research Office of Endourological Society URS Global study.

INTRODUCTION: Ureterorenoscopy (URS) is a popular and growing option for management of ureteric and renal stones. The CROES URS Global Study was set up to assess the outcomes of URS in a large worldwide cohort of patients involving multiple centres. In this paper, we analysed the database for intra-operative and post-operative complications associated with ureterorenoscopy. METHODS: The CROES database was established via collaboration between 114 centres in 32 countries worldwide, and information on both intra-operative and post-operative complications was collected electronically between January 2010 and October 2012. RESULT: On analysis of a total of 11,885 patients, the overall complication and stone-free rates were found to be 7.4 and 85.6 %, respectively. The intra-operative and post-operative complication rates were 4.2 and 2.6 %, respectively, and in total 5 deaths were reported in the study period. Taking into account different world economies, there were no differences in the complication rates between the developing and developed nations or between different centres from different continents. CONCLUSION: Ureterorenoscopy is a safe and effective procedure for treatment of stones, the outcomes of which are broadly comparable in different parts of the world for similar patient and stone demographics.

Testicular Microlithiasis: Patient Compliance in a Two-Year Follow-Up Program.

Introduction: We present a retrospective 2-year follow-up cohort of 103 men with testicular microlithiasis (TML) and discuss patient compliance and the value of surveillance. Methods: A retrospective analysis of patients examined with scrotal ultrasonography (US) in the period from 2008 through 2010 was performed. A total of 103 men with TML were diagnosed and offered US follow-up every 6 months for 2 years. They were retrospectively analyzed regarding demographics and follow-up details, including the development of any kind of malignancy until March 2015, using the Danish Electronic Pathology Registry. Results: The prevalence of TML was 10.3%. Of the 103 men with TML, 23 (22.3%) had TML in the left testicle, 38 (36.9%) in the right (p=0.002), and 42 (40.8%) had bilateral TML. Patient compliance was low with 11.7% participating in all US follow-up examinations. 5 men presented risk factors (testicular atrophy (N=1) and previous testicular cancer (N=4)), but no cases of testicular malignancy were found in the follow-up period. Conclusion: The low patient compliance conflicts with the ESUR Scrotal Imaging Subcommittee guidelines that recommend scrotal US follow-up annually for TML until the age of 55 years. The fact that no cancers were found during follow-up using the pathology registry calls the value of follow-up into question.

Targeted prostate cancer screening in men with mutations in BRCA1 and BRCA2 detects aggressive prostate cancer: preliminary analysis of the results of the IMPACT study.

OBJECTIVE: To evaluate the role of targeted prostate cancer screening in men with BRCA1 or BRCA2 mutations, an international study, IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls), was established. This is the first multicentre screening study targeted at men with a known genetic predisposition to prostate cancer. A preliminary analysis of the data is reported. PATIENTS AND METHODS: Men aged 40-69 years from families with BRCA1 or BRCA2 mutations were offered annual prostate specific antigen (PSA) testing, and those with PSA > 3 ng/mL, were offered a prostate biopsy. Controls were men age-matched (± 5 years) who were negative for the familial mutation. RESULTS: In total, 300 men were recruited (205 mutation carriers; 89 BRCA1, 116 BRCA2 and 95 controls) over 33 months. At the baseline screen (year 1), 7.0% (21/300) underwent a prostate biopsy. Prostate cancer was diagnosed in ten individuals, a prevalence of 3.3%. The positive predictive value of PSA screening in this cohort was 47·6% (10/21). One prostate cancer was diagnosed at year 2. Of the 11 prostate cancers diagnosed, nine were in mutation carriers, two in controls, and eight were clinically significant. CONCLUSIONS: The present study shows that the positive predictive value of PSA screening in BRCA mutation carriers is high and that screening detects clinically significant prostate cancer. These results support the rationale for continued screening in such men.

Irrigation with isoproterenol diminishes increases in pelvic pressure without side-effects during ureterorenoscopy: a randomized controlled study in a porcine model.

OBJECTIVE: Recently, we showed that endoluminally administered isoproterenol (ISO) inhibits muscle function of the pyeloureter in swine. This may be of value in managing increases in pelvic pressure during upper urinary tract endoscopy. The purpose of this study was to examine the effect of endoluminally administered ISO on increases in pelvic pressure and cardiovascular function during flexible ureterorenoscopy. MATERIAL AND METHODS: The study was performed in anaesthetized female pigs. In terms of endoscopic procedures, the pigs were randomized as follows: Group 1, irrigation with 0.1 microg/ml ISO added to saline (n=12); and Group 2, irrigation with saline (n=10). A 5-Fr catheter was retrogradely placed in the renal pelvis and an 8-Fr catheter in the bladder for pressure measurements. Flexible ureterorenoscopy was performed with constant irrigation at a perfusion rate of 8 ml/min. Pelvic, bladder and blood pressure and heart rate were registered continuously. RESULTS: Mean baseline pelvic pressure was identical in both groups: 12+/-2.3 mmHg in Group 1 and 14+/-3.6 mmHg in Group 2 (p=0.26). During ureterorenoscopy, mean pelvic pressure increased to 26+/-2.3 mmHg in Group 1 and to 38+/-3.1 mmHg in Group 2. Hence ISO reduced the pressure increase due to ureterorenoscopy by 42% (p<0.001). Pelvic pressure seemed to be independent of bladder pressure, which showed no difference between the two groups (p=0.067). Blood pressure and heart rate showed no significant differences between the two groups: p=0.425 and p=0.166, respectively. CONCLUSIONS: ISO (0.1 microg/ml) added to irrigation fluid significantly reduces the increase in pelvic pressure during ureterorenoscopy in pigs, without concomitant side-effects.

Renal response to acute acid loading--an organ physiological approach.

OBJECTIVE: In previous studies of the renal response to acute NH4Cl acidosis no correlation was found between systemic acid-base status and the traditionally used quantity, renal net acid excretion (NAE). If NAE is to be considered a physiologically meaningful quantity then this is surprising, as the extracellular acid-base status would be expected to be the key physiological trigger for renal NAE. The object of this study was to investigate the renal response to acute non-carbonic acid loading using a quantitative organ physiological approach. MATERIAL AND METHODS: Five-h NH4Cl loading studies were performed in 10 healthy men using a randomized, placebo-controlled, crossover design. Arterialized capillary blood, serum and urine were collected hourly during the loading studies for the measurement of electrolytes and acid-base status. Concentrations of non-metabolizable base (NB) and acid (NA) were calculated from measured concentrations of non-metabolizable ions according to Kildeberg. RESULTS: In the steady state (placebo) the rate of renal excretion of NA (=-NB) was close to zero, indicating that the net extrarenal input of NA (endogeneous production, gastrointestinal absorption. skeletal release, etc.) was likewise about zero. An inverse correlation was found between blood pH and the rate of renal excretion of NA. Only a small amount of the acid load (approximately 8%) was excreted during the 5-h study period and this was accompanied by massive calciuria, indicating that mobilization of NB from bone contributed substantially to the current net extrarenal NA input. CONCLUSION: From a physiological point of view, NB can be regarded as the actual substrate for renal acid-base control, and measurement of renal turnover of NB may give a more precise description of renal acid-base metabolism during acid loading than previously described methods.

Stone risk after bladder substitution with the ileal-urethral Kock reservoir.

OBJECTIVE: The study was carried out to compare urinary biochemical and physicochemical environments in patients who had undergone bladder substitution with the ileal-urethral Kock reservoir, and who had no actual urinary infection, with those of healthy subjects. MATERIAL AND METHODS: The participants were 23 male patients who had undergone bladder substitution with the ileal-urethral Kock reservoir and 25 healthy men. All subjects had sterile urine at the time of urine collection. Concentrations of calcium, magnesium, phosphorus, creatinine, citrate, oxalate, and ammonia in 24-h urine samples were measured. Estimates of ion activity products of calcium oxalate (CaOx), calcium phosphate (CaP), brushite (Bru), and magnesium ammonium phosphate (MAP) in urine were calculated according to Tiselius. RESULTS: There was no significant difference in 24-h urinary volume between patients with a bladder substitute and the healthy controls. For most of the other measured values the results for patients differed significantly from those for controls. The most striking findings were markedly lower urinary excretion rates of citrate (p < 0.0001) and higher urine pH (p < 0.0001) in patients compared with controls. These findings were reflected in significantly higher levels of urinary supersaturation with respect to CaOx (p < 0.0001), CaP (p <0.0001), Bru (p < 0.0001) and MAP (stuvite) (p < 0.0001) in patients with a bladder substitute compared with healthy subjects. CONCLUSIONS: Hypocitraturia seems to be the main risk factor for calcium stone formation in non-infected Kock reservoir patients, and citrate supplementation appears to be the most obvious choice for stone prophylaxis in patients with intestinal urinary diversion and recurrent renal stone formation.

Hyperoxaluria in idiopathic calcium nephrolithiasis--what are the limits?

OBJECTIVE: The object of this study was to investigate the role for measurement of 24-h renal oxalate excretion in the evaluation of idiopathic calcium stone formers. MATERIALS AND METHODS: Renal excretion rates of oxalate and creatinine were measured in 24-h urines in 46 consecutive male recurrent idiopathic calcium stone formers and 61 healthy males. Furthermore, day-to-day variation in renal oxalate excretion in 10 male recurrent stone formers and 10 healthy males were evaluated by measuring 24-h oxalate excretion on 5 different days in each individual. Concentrations of oxalate in urine were measured using an enzymatic method without ascorbate interference. RESULTS: The cumulative frequency distribution curves of 24-h renal oxalate excretion rates of stone formers and controls were congruent, and there were no statistically significant differences in oxalate excretion rates between stone formers and controls. Mean 24-h oxalate excretion (95%-confidence intervals) was 0.22 (0.18-0.25) mmol and 0.21 (0.18-0.24) mmol in stone formers and controls, respectively (p = 0.9). The day-to-day variation study did not reveal any differences in renal oxalate excretion pattern between stone formers and controls, and the presence of intermittent hyperoxaluria could not be confirmed. The oxalate excretion rates were generally low. CONCLUSION: In our region, there appear to be no differences in 24-h renal excretion rates of oxalate between male recurrent idiopathic calcium stone formers and healthy males, and the syndrome of mild hyperoxaluric calcium nephrolithiasis could not be identified in our population of idiopathic stone formers. Hence, a limit of abnormal oxalate excretion that distinguishes an idiopathic stone former from a non-stone former could not be defined in our population. Therefore, the value of routine measurement of urinary oxalate in idiopathic urolithiasis is difficult to accept, and cannot be recommended.

Metabolic evaluation and medical management of upper urinary tract stone disease. Guidelines from the Scandinavian Cooperative Group for Urinary Stones.

A set of simple guidelines for metabolic evaluation and medical/dietary management of patients with urolithiasis is presented. The evaluation scheme is based on the documented risk factors in the Nordic area and the results of controlled clinical trials, and takes its basis in the severity of the stone disease in the individual stone patient. The initial evaluation in all patients aims at diagnosing conditions with a definitive metabolic, infectious or anatomical/functional cause of stone formation (MIAF urolithiasis). Patients with MIAF urolithiasis are treated according to the nature of the underlying disease. Having excluded/diagnosed MIAF urolithiasis, patients with idiopathic calcium nephrolithiasis remain, and in this group, which comprises approximately 85% of the total stone population in the Scandinavian region, only those with a complicated stone disease are subjected to additional evaluation, which aims at identifying underlying pathophysiological derangements for which medical therapy has been proven to be effective in controlled clinical trials.

Ureteropelvic junction obstruction and ureteral strictures treated by simple high-pressure balloon dilation.

The long-term results of simple high-pressure balloon dilation in the treatment of ureteropelvic junction obstruction (UPJO) and ureteral strictures were evaluated. A total of 77 consecutive patients were treated: 40 had UPJO and 37 ureteral strictures. The etiology of the obstruction included congenital UPJO, previous stones, sequelae of endoscopic and open surgery, radiotherapy, and urinary tract reconstruction. A retrograde ureteroscopic approach was used. Evaluation included clinical and radiographic examinations and renal scintigraphy with diuretic wash-out. The procedure was repeated in 21 cases. The median follow-up was 29 months. The procedure was considered successful if it left the patient asymptomatic and with improved renographic function and drainage. The overall success rate was 70%. The best results were obtained in strictures secondary to stones, with a success rate of 94%, and in strictures secondary to reconstructive and ureteroscopic surgery, with a success rate of 91%. In congenital UPJO, the results were less encouraging: in patients with a symptom debut after the age of 18 years, balloon dilation was successful in 57% of cases; in patients with symptom debut before the age of 18 years, success was achieved in only 25% of cases. There were no major complications. It was concluded that simple high-pressure balloon dilation is a safe and reasonably effective technique for the management of most ureteral strictures and congenital UPJO with symptom debut in adult life. Balloon dilation seems to have no place in the treatment of primary congenital UPJO in children.

[Polyglyconate or polyglycolic acid suture in patients with suspected impaired wound healing]. / Polyglykonat- eller polyglykolsyresutur hos patienter med forventet haemmet sårheling.

A randomized study of abdominal fascial closure using interrupted polyglyconate and polyglycolic acid sutures after laparotomy was carried out in 204 consecutive patients with suspected impaired wound healing. There were no statistically significant differences between the two sutures with regard to development of fascial disruption and incisional hernia. Wound infection demanding surgical intervention was found in 7% of patients with polyglyconate sutures and in 16% of those with polyglycolic acid sutures (p = 0.04). Monofilament polyglyconate suture does not reduce the incidence of fascial disruption and incisional hernia after laparotomy in patients with suspected impaired wound healing but the incidence of wound infection may be reduced compared with that of multifilament polyglycolic acid suture.

An electron microscopic study of clinical Paget's disease of the nipple.

An ultrastructural study of the epidermis from eight patients with clinical Paget's disease of the nipple supports the epidermotropic theory. There was no evidence that the Paget's cells originated from keratinocytes. We propose the hypothesis that Paget's cells represent transformed ductal cells, from the subjacent lactiferous ducts of the nipple, which have migrated into the epidermis, either as neoplastic cells or as normal ductal cells with secondary in situ transformation in the epidermis.

Randomized comparison of polyglycolic acid and polyglyconate sutures for abdominal fascial closure after laparotomy in patients with suspected impaired wound healing.

A randomized study of abdominal fascial closure using interrupted polyglyconate and polyglycolic acid sutures after laparotomy was carried out in 204 consecutive patients with suspected impaired wound healing. There were no statistically significant differences between the two sutures with regard to the development of fascial disruption and incisional hernia. Wound infection demanding surgical intervention was found in 7 per cent of patients with polyglyconate sutures and in 16 per cent of those with polyglycolic acid sutures (P = 0.04). Monofilament polyglyconate suture does not reduce the incidence of fascial disruption and incisional hernia after laparotomy in patients with suspected impaired wound healing but the incidence of wound infection may be reduced compared with that of multifilament polyglycolic acid suture.

Urinary acidification and urinary excretion of calcium and citrate in women with bilateral medullary sponge kidney.

Urinary acidification ability, acid-base status and urinary excretion of calcium and citrate were evaluated in 10 women with bilateral medullary sponge kidney (MSK) and in 10 healthy women. Patients with MSK had higher fasting urine pH compared to normal controls (p < 0.01). Four patients had incomplete renal tubular acidiosis (iRTA), 3 had hypercalciuria, and 5 patients had hypocitraturia. The 24-hour urinary excretion of calcium was increased in the females with MSK (5.23 +/- 0.78 mmol) compared to the healthy females (3.49 +/- 0.29 mmol) (p < 0.02), and increased in MSK patients with iRTA (7.32 +/- 1.45 mmol) compared to patients with normal urinary acidification (3.83 +/- 0.12 mmol) (p < 0.01). The patients with iRTA had reduced levels of plasma standard bicarbonate (20.5 +/- 1.0) after fasting compared to patients with normal urinary acidification (23.8 +/- 0.8) and healthy women (22.7 +/- 0.6) (p < 0.01), and reduced levels of 24-hour urinary excretion of citrate (0.93 +/- 0.25 mmol) compared to patients with normal urinary acidification (3.58 +/- 0.51) and healthy women (2.78 +/- 0.49) (p < 0.005). A positive correlation was found between the degree of acidosis during ammonium chloride loading and urinary excretion of calcium (r = 0.71, p = 0.02), and a negative correlation between the degree of acidosis during ammonium chloride loading and urinary citrate excretion (r = 0.87, p = 0.001). The results suggest that defective urinary acidification might play an important role in the mechanism of hypercalciuria and hypocitraturia in patients with medullary sponge kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

[Citrate and kidney stones]. / Citrat og nyresten.

Citrate is an important naturally occurring inhibitor of calcium stone formation in urine. Urinary citrate excretion was examined in 43 consecutive patients with recurrent idiopathic calcium nephrolithiasis and in 50 normal controls by a specific enzymatic technique. Hypocitraturia (< 1.6 mmol/24h) was found in 14 (33%) stone formers compared to 6 (12%) normal controls (p = 0.03). Citrate excretion expressed as citrate-creatinine ratio in 24 hour urine samples was significantly lower in the stone formers than in the healthy controls (p = 0.03), and significantly lower in healthy men, compared to healthy females (p = 0.006). There was a great variability in urinary citrate levels in both groups, and a considerable overlap in the urinary citrate excretion between normal subjects and stone formers. Factors other than urinary citrate excretion must therefore be of importance in the pathophysiology of calcium stone formation. Citrate-calcium ratio in urine proved to be a reliable index in discriminating stone formers from healthy subjects.