Management of urinary stones: state of the art and future perspectives by experts in stone disease.

AIM: To present state of the art on the management of urinary stones from a panel of globally recognized urolithiasis experts who met during the Experts in Stone Disease Congress in Valencia in January 2024. Options of treatment: The surgical treatment modalities of renal and ureteral stones are well defined by the guidelines of international societies, although for some index cases more alternative options are possible. For 1.5 cm renal stones, both m-PCNL and RIRS have proven to be valid treatment alternatives with comparable stone-free rates. The m-PCNL has proven to be more cost effective and requires a shorter operative time, while the RIRS has demonstrated lower morbidity in terms of blood loss and shorter recovery times. SWL has proven to be less effective at least for lower calyceal stones but has the highest safety profile. For a 6mm obstructing stone of the pelviureteric junction (PUJ) stone, SWL should be the first choice for a stone less than 1 cm, due to less invasiveness and lower risk of complications although it has a lower stone free-rate. RIRS has advantages in certain conditions such as anticoagulant treatment, obesity, or body deformity. Technical issues of the surgical procedures for stone removal: In patients receiving antithrombotic therapy, SWL, PCN and open surgery are at elevated risk of hemorrhage or perinephric hematoma. URS, is associated with less morbidity in these cases. An individualized combined evaluation of risks of bleeding and thromboembolism should determine the perioperative thromboprophylactic strategy. Pre-interventional urine culture and antibiotic therapy are mandatory although UTI treatment is becoming more challenging due to increasing resistance to routinely applied antibiotics. The use of an intrarenal urine culture and stone culture is recommended to adapt antibiotic therapy in case of postoperative infectious complications. Measurements of temperature and pressure during RIRS are vital for ensuring patient safety and optimizing surgical outcomes although techniques of measurements and methods for data analysis are still to be refined. Ureteral stents were improved by the development of new biomaterials, new coatings, and new stent designs. Topics of current research are the development of drug eluting and bioresorbable stents. Complications of endoscopic treatment: PCNL is considered the most invasive surgical option. Fever and sepsis were observed in 11 and 0.5% and need for transfusion and embolization for bleeding in 7 and 0.4%. Major complications, as colonic, splenic, liver, gall bladder and bowel injuries are quite rare but are associated with significant morbidity. Ureteroscopy causes less complications, although some of them can be severe. They depend on high pressure in the urinary tract (sepsis or renal bleeding) or application of excessive force to the urinary tract (ureteral avulsion or stricture). Diagnostic work up:  Genetic testing consents the diagnosis of monogenetic conditions causing stones. It should be carried out in children and in selected adults. In adults, monogenetic diseases can be diagnosed by systematic genetic testing in no more than 4%, when cystinuria, APRT deficiency, and xanthinuria are excluded. A reliable stone analysis by infrared spectroscopy or X-ray diffraction is mandatory and should be associated to examination of the stone under a stereomicroscope. The analysis of digital images of stones by deep convolutional neural networks in dry laboratory or during endoscopic examination could allow the classification of stones based on their color and texture. Scanning electron microscopy (SEM) in association with energy dispersive spectrometry (EDS) is another fundamental research tool for the study of kidney stones. The combination of metagenomic analysis using Next Generation Sequencing (NGS) techniques and the enhanced quantitative urine culture (EQUC) protocol can be used to evaluate the urobiome of renal stone formers. Twenty-four hour urine analysis has a place during patient evaluation together with repeated measurements of urinary pH with a digital pH meter. Urinary supersaturation is the most comprehensive physicochemical risk factor employed in urolithiasis research. Urinary macromolecules can act as both promoters or inhibitors of stone formation depending on the chemical composition of urine in which they are operating. At the moment, there are no clinical applications of macromolecules in stone management or prophylaxis. Patients should be evaluated for the association with systemic pathologies. PROPHYLAXIS: Personalized medicine and public health interventions are complementary to prevent stone recurrence. Personalized medicine addresses a small part of stone patients with a high risk of recurrence and systemic complications requiring specific dietary and pharmacological treatment to prevent stone recurrence and complications of associated systemic diseases. The more numerous subjects who form one or a few stones during their entire lifespan should be treated by modifications of diet and lifestyle. Primary prevention by public health interventions is advisable to reduce prevalence of stones in the general population. Renal stone formers at "high-risk" for recurrence need early diagnosis to start specific treatment. Stone analysis allows the identification of most "high-risk" patients forming non-calcium stones: infection stones (struvite), uric acid and urates, cystine and other rare stones (dihydroxyadenine, xanthine). Patients at "high-risk" forming calcium stones require a more difficult diagnosis by clinical and laboratory evaluation. Particularly, patients with cystinuria and primary hyperoxaluria should be actively searched. FUTURE RESEARCH: Application of Artificial Intelligence are promising for automated identification of ureteral stones on CT imaging, prediction of stone composition and 24-hour urinary risk factors by demographics and clinical parameters, assessment of stone composition by evaluation of endoscopic images and prediction of outcomes of stone treatments. The synergy between urologists, nephrologists, and scientists in basic kidney stone research will enhance the depth and breadth of investigations, leading to a more comprehensive understanding of kidney stone formation.

Precision Medicine in Castration-Resistant Prostate Cancer: Advances, Challenges, and the Landscape of PARPi Therapy-A Narrative Review.

After recent approvals, poly-adenosine diphosphate [ADP]-ribose polymerase inhibitors (PARPis) have emerged as a frontline treatment for metastatic castration-resistant prostate cancer (mCRPC). Unlike their restricted use in breast or ovarian cancers, where approval is limited to those with BRCA1/2 alterations, PARPis in mCRPC are applied across a broader spectrum of genetic aberrations. Key findings from the phase III PROPEL trial suggest that PARPis' accessibility may broaden, even without mandatory testing. An increasing body of evidence underscores the importance of distinct alterations in homologous recombination repair (HRR) genes, revealing unique sensitivities to PARPis. Nonetheless, despite the initial effectiveness of PARPis in treating BRCA-mutated tumors, resistance to therapy is frequently encountered. This review aims to discuss patient stratification based on biomarkers and genetic signatures, offering insights into the nuances of first-line PARPis' efficacy in the intricate landscape of mCRPC.

Acute intestinal pseudo-obstruction by pheochromocytoma: A case report with review of literature.

INTRODUCTION: Pheochromocytomas are rare tumors of the adrenal gland. Intestinal pseudo-obstruction is a very rare presentation of a functioning catecholamine-secreting tumor. We present a case of intestinal pseudo-obstruction due to a large functioning pheochromocytoma. CASE REPORT: A 29-year-old female presented with abdominal distension, pain, nausea, and vomiting with constipation for 3 weeks. She was hypertensive and diabetic and was on multiple medications. She reported frequent spells of severe headaches, palpitations, night sweats, and a 17 kg weight loss over 6 months. She had pallor, dyspnea, marked abdominal distension, and diminished bowel sounds. Her blood pressure was high at 200/120 mmHg. She had tachycardia (pulse 120 bpm) and tachypnea (35 pm). Serum metanephrine levels were significantly elevated, measuring 1203 pg/ml. Abdominal CT showed a heterogeneous, hyper-vascular mass near the upper pole of the left kidney, measuring 10.75 cm × 8.72 cm. Open left adrenalectomy was performed through an anterior subcostal approach to remove the tumor with the left adrenal gland. Histopathological examinations were consistent with pheochromocytoma. DISCUSSION: Some authors documented the correlation between tumor size and metabolic activity of catecholamine-secreting tumors with intestinal pseudo-obstruction by paralytic ileus. This case corresponds with these findings, with a tumor mass of 350 g and a serum metanephrine level of 1203 pg/ml. CONCLUSION: Although it is extremely rare, functioning pheochomocytoma could be a cause of instestinal obstruction or pseudo-obstruction.

Spectrum of Bacterial Pathogens from Urinary Infections Associated with Struvite and Metabolic Stones.

OBJECTIVE: The purposes of this multi-center study were to evaluate the rate of infection stones and to evaluate the urine cultures of patients with infection stones. MATERIALS: Charts of adulpatients with urinary stones were reviewed and data on stone analyses and urine cultures were collected. RESULTS: In total, 1204 renal stone formers (RSFs) from 10 countries were included (776 males, 428 females). Fifty-six patients (4.6%) had struvite stones. The highest frequency of struvite stones was observed in India (23%) and Pakistan (18%). Lower rates were reported in Canada (2%), China (3%), Argentina (3%), Iraq (3%), Italy (3.5%) and Poland (3%), and intermediate rates in Egypt (5.5%) and Bulgaria (5.4%). Urine cultures were retrieved from 508 patients. Patients with struvite stones had a positive culture in 64.3% of the samples and patients with other stones, in 26.7%. In struvite stones, the most common isolates were Escherichia coli (27.7%) and Proteus spp. (27.7%), followed by Klebsiella spp. (16.7%); in other types of stone, it was Escherichia coli (47.6%), followed by Gram-positive bacteria (14.0%) Conclusions: The struvite stone composition was associated with a urinary infection, although an infection was not demonstrable with a conventional midstream urine culture in about 30%.

Stone composition of renal stone formers from different global regions.

OBJECTIVE: To study urinary stone composition patterns in different populations around the world. MATERIALS AND METHODS: Data were collected by reviewing charts of 1204 adult patients of 10 countries with renal or ureteral stones (> 18 years) in whom a stone analysis was done and available. Any method of stone analysis was accepted, but the methodology had to be registered. RESULTS: In total, we observed 710 (59%) patients with calcium oxalate, 31 (1%) with calcium phosphate, 161 (13%) with mixed calcium oxalate/calcium phosphate, 15 (1%) with carbapatite, 110 (9%) with uric acid, 7 (< 1%) with urate (ammonium or sodium), 100 (9%) with mixed with uric acid/ calcium oxalate, 56 (5%) with struvite and 14 (1%) with cystine stones. Calciumcontaining stones were the most common in all countries ranging from 43 to 91%. Oxalate stones were more common than phosphate or mixed phosphate/oxalate stones in most countries except Egypt and India. The rate of uric acid containing stones ranged from 4 to 34%, being higher in Egypt, India, Pakistan, Iraq, Poland and Bulgaria. Struvite stones occurred in less than 5% in all countries except India (23%) and Pakistan (16%). Cystine stones occurred in 1% of cases. CONCLUSIONS: The frequency of different types of urinary stones varies from country to country. Calcium-containing stones are prevalent in all countries. The frequency of uric acid containing stones seems to depend mainly on climatic factors, being higher in countries with desert or tropical climates. Dietary patterns can also lead to an increase in the frequency of uric acid containing stones in association with high obesity rates. Struvite stones are decreasing in most countries due to improved health conditions.

Obesity rates in renal stone formers from various countries.

OBJECTIVE: To collect evidence on the rate of obesity in renal stone formers (RSFs) living in different climatic areas and consuming different diets. MATERIALS AND METHODS: Data of adult renal stone formers were retrospectively collected by members of U-merge from 13 participant centers in Argentina, Brazil, Bulgaria (2), China, India, Iraq (2), Italy (2), Nigeria, Pakistan and Poland. The following data were collected: age, gender, weight, height, stone analysis and procedure of stone removal. RESULTS: In total, 1689 renal stone formers (1032 males, 657 females) from 10 countries were considered. Average age was 48 (±14) years, male to female ratio was 1.57 (M/F 1032/657), the average body mass index (BMI) was 26.5 (±4.8) kg/m2. The obesity rates of RSFs in different countries were significantly different from each other. The highest rates were observed in Pakistan (50%), Iraq (32%), and Brazil (32%), while the lowest rates were observed in China (2%), Nigeria (3%) and Italy (10%). Intermediate rates were observed in Argentina (17%), Bulgaria (17%), India (15%) and Poland (22%). The age-adjusted obesity rate of RSFs was higher than the age-adjusted obesity rate in the general population in Brazil, India, and Pakistan, whereas it was lower in Argentina, Bulgaria, China, Italy, and Nigeria, and similar in Iraq and Poland. CONCLUSIONS: The age-adjusted obesity rate of RSFs was not higher than the age-adjusted obesity rate of the general population in most countries. The relationship between obesity and the risk of kidney stone formation should be reconsidered by further studies carried out in different populations.

The role of radiological surveillance in the conservative management of incidental small testicular masses: A systematic review.

Objective: The increasing use of scrotal ultrasonography (US) for non-cancerous indications has led to greater detection of incidental, small testicular masses. Operative intervention is currently the mainstay of treatment for all testicular tumours; however, despite the low malignant potential of small, incidental masses, little is known about conservative management using radiological surveillance. Methods: A systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted and studies meeting the inclusion criteria were reviewed for patient outcomes. Results: A total of 293 patients across six studies underwent radiological surveillance for an incidental small testicular mass. Infertility was the main indication for investigation and all studies used US as the surveillance modality. A total of 37 patients (12.6%) underwent surgical exploration during follow-up, with only 10 (3.4%) found to have malignant disease at histology. Conclusions: Radiological surveillance of incidental small testicular masses is safe when used for select patient groups due to the high probability of benign disease, although optimal patient selection criteria and a well-defined protocol are lacking. This approach could be considered in patients with incidental, impalpable testicular masses of ≤5 mm in diameter displaying no significant size increase or internal vascularity on US and with negative tumour markers, as the probability of malignancy in these patients is low.

Polymorphisms in androgen metabolism genes AR, CYP1B1, CYP19, and SRD5A2and prostate cancer risk and aggressiveness in Bulgarian patients.

BACKGROUND/AIM: The aim of our study was to elucidate the role of polymorphisms in AR, CYP1B1, CYP19, and SRD5A2 genes for prostate cancer (PC) development in Bulgarian patients. MATERIALS AND METHODS: We genotyped 246 PC patients and 261 controls (155 with benign prostate hyperplasia and 107 healthy population controls) using direct sequencing, PCR-RFLP, SSCP, and fragment analysis. RESULTS: The allele and genotype frequencies of most of the studied variants did not differ significantly between cases and controls. Increased frequencies of the C/C genotype and C allele of rs1056837 in CYP1B1, and genotype 7/8 of the (TTTA)n repeat polymorphism in CYP19, were observed in patients in comparison with controls.The 8/9 and the 7/12 genotypes of (TTTA)n in CYP19 showed suggestive evidence for association with decreased prostate cancer risk and the risk for aggressive disease, respectively. The haplotype analysis revealed 2 CYP1B1 haplotypes associated with PC risk reduction. CONCLUSION: Some CYP1B1 haplotypes and genotypes of the CYP19 (TTTA)n repeat appeared to be associated with disease risk or aggressiveness in Bulgarian PC patients. In contrast, the SRD5A2 polymorphisms (V89L and (TA)n repeat), the CAG repeat in AR, and the Arg264Cys variant in CYP19A1 are most likely not implicated in prostate carcinogenesis.

Combinations of serum prostate-specific antigen and plasma expression levels of let-7c, miR-30c, miR-141, and miR-375 as potential better diagnostic biomarkers for prostate cancer.

In the current study, expression levels of let-7c, miR-30c, miR-141, and miR-375 in plasma from 59 prostate cancer (PC) patients with different clinicopathological characteristics and two groups of controls: 16 benign prostatic hyperplasia (BPH) samples and 11 young asymptomatic men (YAM) were analyzed to evaluate their diagnostic and prognostic value in comparison to prostate-specific antigen (PSA). miR-375 was significantly downregulated in 83.5% of patients compared to BPH controls and showed stronger diagnostic accuracy (area under the curve [AUC]=0.809, 95% CI: 0.697-0.922, p=0.00016) compared with PSA (AUC=0.710, 95% CI: 0.559-0.861, p=0.013). Expression levels of let-7c showed potential to distinguish PC patients from BPH controls with AUC=0.757, but the result did not reach significance. Better discriminating performance was observed when combinations of studied biomarkers were used. Sensitivity of 86.8% and specificity of 81.8% were reached when all biomarkers were combined (AUC=0.877) and YAM were used as calibrators. None of the studied microRNAs (miRNAs) showed correlation with clinicopathological characteristics. PSA levels were significantly correlated with the Gleason score, tumor stage, and lymph node metastasis with Spearman correlation coefficients: 0.612, 0.576, and 0.458. In conclusion, the combination of the studied circulating plasma miRNAs and serum PSA has the potential to be used as a noninvasive diagnostic biomarker for PC screening outperforming the PSA testing alone.

Laparoscopic varicocelectomy in the management of chronic scrotal pain.

BACKGROUND AND OBJECTIVES: To evaluate the usefulness of laparoscopic varicocelectomy in the management of chronic scrotal pain. METHODS: Between 2009 and 2011, 48 patients in total were treated with laparoscopic varicocelectomy for dull scrotal pain that worsened with physical activity and was attributed to varicoceles. All patients were followed up at 3 and 6 months and biannually thereafter with a physical examination, visual analog scale score, and ultrasonographic scan in selected cases. RESULTS: The mean age was 38.2 years (range, 23-54 years). The mean follow-up period was 19.6 months (range, 6-26 months). Bilateral varicoceles were present in 7 patients (14.6%), and a unilateral varicocele was present in 41 (85.4%). The varicocele was grade 3 in 27 patients (56.3%), grade 2 in 20 (41.6%), and grade 1 in 1 (2.1%). The mean preoperative visual analog scale score was 4.8 on a scale from 0 to 10. The mean postoperative visual analog scale score at 3 months was 0.8. After the procedure, 42 patients (87.5%) had a significant improvement in the visual analog scale score (P<.001); 5 (10.4%) had symptom improvement, although it was not statistically significant; and 1 (2.1%) remained unchanged. During follow-up, we observed 5 recurrences (10.4%) whereas de novo hydrocele formation was identified in 4 individuals (8.3%). CONCLUSION: Laparoscopic varicocelectomy is efficient in the treatment of symptomatic varicoceles with a low complication rate. However, careful patient selection is necessary because it appears that individuals presenting with sharp, radiating testicular pain and/or a low-grade varicocele are less likely to benefit from this procedure.

Efficacy of tamsulosin oral controlled absorption system after extracorporeal shock wave lithotripsy to treat urolithiasis.

OBJECTIVE: To determine the efficacy of the tamsulosin oral controlled absorption system as an adjuvant therapy to extracorporeal shock wave lithotripsy (ESWL) for the expulsion of ureteral and renal stones. METHODS: A consecutive sample of 248 patients with ureteral or renal stones who underwent ESWL in an academic hospital was included in a 12-week, prospective, open-label, randomized clinical trial. Of the 248 patients, 186, including 77 with ureteral stones (mean size 9 mm) and 109 with renal stones (mean size 13 mm) completed the study. After successful ESWL, the patients were randomized to standard medical care (corticosteroids and analgesics) or standard care plus the tamsulosin oral controlled absorption system 0.4 mg/d for 1 month. The stone clearance rate, interval to the elimination of stone fragments, incidence of renal colic, and the need for rehospitalization were assessed at 4, 8, and 12 weeks. RESULTS: The stone clearance rate was significantly greater for the patients treated with tamsulosin than for those in the standard care group at 4 (73.4% vs 55.9%, respectively; P < .001) and 12 (91.3% vs 74.6%, respectively; P < .05) weeks. Tamsulosin treatment was also associated with a significantly lower interval to the elimination of stone fragments (P < .001), a significantly lower rehospitalization rate (P < .001), and a significantly lower proportion of patients with acute renal colic (P < .05) than standard care alone. No severe adverse events leading to treatment discontinuation were observed. CONCLUSION: Adjuvant treatment with tamsulosin, in addition to standard treatment with steroids and analgesics, improved the outcome of ESWL.

Malignant melanoma of glans penis and prepuce treated with organ-preserving surgical procedure.

The authors present a case of malignant melanoma of glans penis and prepuce. An organ-preserving operative procedure using buccal mucosa was performed with subsequent inguino-femoral modified lymphadenectomy. There was no disease progression during the follow-up period of twelve months.

Liquid chromatography method for simultaneous analysis of amino acids and biogenic amines in biological fluids with simultaneous gradient of pH and acetonitrile.

A liquid chromatography method for simultaneous analysis of amino acids, polyamines, catecholeamines and metanephrines in human body fluids after derivatization with 9-fluorenylmethyloxycarbonyl chloride was developed. The chromatographic behavior of analytes at different pH of mobile phase was studied. Successful baseline resolution of all analyzed compounds was achieved using simultaneous gradient of pH and organic modifier in reverse phase mode of HPLC within 36 min. The repeatability of the proposed procedure in respect of retention time and peak area, expressed as RSD, ranges from 0.06 to 1.64% and 0.4 to 7.6%, respectively. The method linearity in the range of 1-200 microM for amino acids and in the range of 0.1-20 microM for polyamines, catecholeamines and metanephrines was found to be with correlation coefficients higher than 0.994. The limit of quantification (LOQ) was assessed to be in the range of 2.6-10 pmol for amino acids and 2-4 pmol for polyamines, catecholeamines and metanephrines.

Case of duplication of the urethra in an adult male, presenting with symptoms of bladder outlet obstruction.

Duplication of the urethra is a rare congenital anomaly, usually found in children and adolescents. The authors present a rare case of urethral duplication, presenting in a 58-yr-old man, with symptoms of bladder outlet obstruction.