Giant Retroperitoneal Mucinous Tumor Supportively Diagnosed as a Dedifferentiated Liposarcoma by Fluorescence In Situ Hybridization of MDM2 Gene

Surgical resection was performed on a 47-year-old woman for a retroperitoneal mass that weighed 8.5 kg. Histological examination revealed a myxoid sarcomatous tumor. Because diagnosis could not be determined by immunohistochemistry, attention was focused on MDM2 (murine double minute) gene amplification by fluorescence in situ hybridization (FISH) analysis. The tumor was finally determined to be a dedifferentiated liposarcoma. We experienced a case of a giant retroperitoneal dedifferentiated liposarcoma. FISH analysis was useful for the diagnosis and determination of the therapeutic strategy

PHYOX2: a pivotal randomized study of nedosiran in primary hyperoxaluria type 1 or 2

Chronic kidney disease; Pediatric nephrology; UrologyMalaltia renal crònica; Nefrologia pediàtrica; UrologiaEnfermedad renal crónica; Nefrología pediátrica; UrologíaNedosiran is an investigational RNA interference agent designed to inhibit expression of hepatic lactate dehydrogenase, the enzyme thought responsible for the terminal step of oxalate synthesis. Oxalate overproduction is the hallmark of all genetic subtypes of primary hyperoxaluria (PH). In this double-blind, placebo-controlled study, we randomly assigned (2:1) 35 participants with PH1 (n = 29) or PH2 (n = 6) with eGFR ≥30 mL/min/1.73 m2 to subcutaneous nedosiran or placebo once monthly for 6 months. The area under the curve (AUC) of percent reduction from baseline in 24-hour urinary oxalate (Uox) excretion (primary endpoint), between day 90–180, was significantly greater with nedosiran vs placebo (least squares mean [SE], +3507 [788] vs −1664 [1190], respectively; difference, 5172; 95% CI 2929–7414; P < 0.001). A greater proportion of participants receiving nedosiran vs placebo achieved normal or near-normal (<0.60 mmol/24 hours; <1.3 × ULN) Uox excretion on ≥2 consecutive visits starting at day 90 (50% vs 0; P = 0.002); this effect was mirrored in the nedosiran-treated PH1 subgroup (64.7% vs 0; P < 0.001). The PH1 subgroup maintained a sustained Uox reduction while on nedosiran, whereas no consistent effect was seen in the PH2 subgroup. Nedosiran-treated participants with PH1 also showed a significant reduction in plasma oxalate versus placebo (P = 0.017). Nedosiran was generally safe and well tolerated. In the nedosiran arm, the incidence of injection-site reactions was 9% (all mild and self-limiting). In conclusion, participants with PH1 receiving nedosiran had clinically meaningful reductions in Uox, the mediator of kidney damage in PH

The impact of crystal phase transition on the hardness and structure of kidney stones

The version of record of this article, first published in Urolithiasis, is available online at Publisher’s website: https://doi.org/10.1007/s00240-024-01556-5.Calcium oxalate kidney stones, the most prevalent type of kidney stones, undergo a multi-step process of crystal nucleation, growth, aggregation, and secondary transition. The secondary transition has been rather overlooked, and thus, the effects on the disease and the underlying mechanism remain unclear. Here, we show, by periodic micro-CT images of human kidney stones in an ex vivo incubation experiment, that the growth of porous aggregates of calcium oxalate dihydrate (COD) crystals triggers the hardening of the kidney stones that causes difficulty in lithotripsy of kidney stone disease in the secondary transition. This hardening was caused by the internal nucleation and growth of precise calcium oxalate monohydrate (COM) crystals from isolated urine in which the calcium oxalate concentrations decreased by the growth of COD in closed grain boundaries of COD aggregate kidney stones. Reducing the calcium oxalate concentrations in urine is regarded as a typical approach for avoiding the recurrence. However, our results revealed that the decrease of the concentrations in closed microenvironments conversely promotes the transition of the COD aggregates into hard COM aggregates. We anticipate that the suppression of the secondary transition has the potential to manage the deterioration of kidney stone disease

Evidence for Solution-Mediated Phase Transitions in Kidney Stones: Phase Transition Exacerbates Kidney Stone Disease

Maruyama M., Tanaka Y., Momma K., et al. Evidence for Solution-Mediated Phase Transitions in Kidney Stones: Phase Transition Exacerbates Kidney Stone Disease. Crystal Growth and Design 23, 4285 (2023); https://doi.org/10.1021/acs.cgd.3c00108.In this study, we investigated calcium oxalate (CaOx) kidney stones and showed direct evidence of the solution-mediated phase transition of calcium oxalate dihydrate (COD; the metastable phase) to calcium oxalate monohydrate (COM; the stable phase). We examined the crystal phases, crystal textures, and protein distributions within thin sections of calcium oxalate kidney stones. Observation with a polarized-light microscope showed that the outline of the mosaic texture, in which COM crystals are assembled in a mosaic pattern, roughly coincides with COD’s crystallographically stable face angles. Microfocus X-ray CT measurement captured the intermediate process of the phase transition, starting inside the COD single crystal and gradually transforming to COM crystals. In addition, the distribution of osteopontin and prothrombin fragment-1, common proteins contained in urine and visualized by multicolor fluorescence immunostaining, showed no apparent striations inside the COM single crystals with the mosaic texture, although the striation is apparent inside the COD single crystals. This is probably because the phase transition of mosaic-like COM occurred in a semiclosed system inside the COD single crystal, so the effect of periodic (day-night, seasonal, etc.) urinary protein concentration changes was small. On the other hand, striations were visible in concentrically laminated COM. This indicated that concentrically laminated COM formed in response to the changes in urinary protein concentrations. From the above, we conclude that the COD single crystals and the concentrically laminated COM seen in CaOx stones are primary structures, and the mosaic COM is a secondary structure that is a pseudomorph formed by the solution-mediated phase transition from COD single crystals

PHYOX2: a pivotal randomized study of nedosiran in primary hyperoxaluria type 1 or 2

Nedosiran is an investigational RNA interference agent designed to inhibit expression of hepatic lactate dehydrogenase, the enzyme thought responsible for the terminal step of oxalate synthesis. Oxalate overproduction is the hallmark of all genetic subtypes of primary hyperoxaluria (PH). In this double-blind, placebo-controlled study, we randomly assigned (2:1) 35 participants with PH1 (n = 29) or PH2 (n = 6) with eGFR ≥30 mL/min/1.73 m2 to subcutaneous nedosiran or placebo once monthly for 6 months. The area under the curve (AUC) of percent reduction from baseline in 24-hour urinary oxalate (Uox) excretion (primary endpoint), between day 90-180, was significantly greater with nedosiran vs placebo (least squares mean [SE], +3507 [788] vs -1664 [1190], respectively; difference, 5172; 95% CI 2929-7414; P < 0.001). A greater proportion of participants receiving nedosiran vs placebo achieved normal or near-normal (<0.60 mmol/24 hours; <1.3 × ULN) Uox excretion on ≥2 consecutive visits starting at day 90 (50% vs 0; P = 0.002); this effect was mirrored in the nedosiran-treated PH1 subgroup (64.7% vs 0; P < 0.001). The PH1 subgroup maintained a sustained Uox reduction while on nedosiran, whereas no consistent effect was seen in the PH2 subgroup. Nedosiran-treated participants with PH1 also showed a significant reduction in plasma oxalate versus placebo (P = 0.017). Nedosiran was generally safe and well tolerated. In the nedosiran arm, the incidence of injection-site reactions was 9% (all mild and self-limiting). In conclusion, participants with PH1 receiving nedosiran had clinically meaningful reductions in Uox, the mediator of kidney damage in PH

Single-Session Impact of High-Power Laser with Moses Technology for Lower Pole Stones in Retrograde Intrarenal Surgery: Retrospective Study

Background: This study aimed to evaluate the efficacy of a high-power holmium laser with Moses technology (MT) for the treatment of lower pole stones during retrograde intrarenal surgery (RIRS). Methods: Herein, 305 patients with lower pole stones who underwent RIRS using a high-power holmium laser with MT were retrospectively classified into the stone-free (SF) and non-SF groups. We measured the stone burden, stone volume, stone hardness, pre- or post-operative stent placement, infundibulopelvic angle (IPA), infundibular width (IW), infundibular length (IL), and calyceal pelvic height in terms of pelvicalyceal anatomy using retrograde pyelograms and evaluated the predictive factors of postoperative SF. Results: A total of 173 (56.7%) and 229 (75.1%) patients achieved a SF status on postoperative day one and at one month, respectively. Operation time in the SF group was shorter than that in the non-SF group (51.0 vs. 74.5 min). There were no significant differences in postoperative complications between the SF and non-SF groups. Significantly predictive risk factors in postoperative SF included total stone volume (odds ratio (OR), 1.056; 95% CI, 1.015–1.099; p = 0.007), IPA (OR, 0.970; 95% CI, 0.956–0.993; p = 0.009), and IW (OR, 0.295; 95% CI, 0.121–0.718; p = 0.007). The cut-off values of stone volume, IPA, and IW were 515.2 mm3, 46.8°, and 7.75 mm, respectively. Conclusions: A high-power holmium laser with MT in lower pole stones is a valuable option for positive outcomes and patient’s safety. Larger stone volume, acute IPA, and narrow IW were negative predictors related to postoperative SF status

Urothelial carcinoma occurring in a defunctionalized bladder after urinary diversion due to the bladder exstrophy‐epispadias complex

Introduction The bladder exstrophy‐epispadias complex is a rare congenital disease. Urothelial carcinomas rarely occur in patients with this disease, and there have been few reports on its treatment. Case presentation We report the case of a 44‐year‐old man with a hemorrhage from the external urethral meatus. He was diagnosed with bladder exstrophy‐epispadias complex and underwent urinary diversion with substitution cystoplasty and Mitrofanoff appendicovesicostomy. Because computed tomography and magnetic resonance imaging suggested invasive bladder carcinoma in the defunctionalized bladder, we performed a cystectomy. The patient was diagnosed with urothelial carcinoma with glandular differentiation. One month after the surgery, nivolumab adjuvant chemotherapy was administered. The patient showed no signs of recurrence or metastasis after the treatment. Conclusion This is the first case of adjuvant nivolumab therapy for urothelial carcinoma with the bladder exstrophy‐epispadias complex

Kidney stone formers have more renal parenchymal crystals than non-stone formers, particularly in the papilla region

Abstract Background We investigated the renoprotective ability of healthy people against kidney stone formation. To clarify intratubular crystal kinetics and processing in human kidneys, we performed a quantitative and morphological observation of nephrectomized renal parenchyma tissues. Methods Clinical data and pathological samples from 60 patients who underwent radical nephrectomy for renal cancer were collected from June 2004 to June 2010. The patients were retrospectively classified as stone formers (SFs; n = 30, kidney stones detected by preoperative computed tomography) and non-stone formers (NSFs; n = 30, no kidney stone history). The morphology of parenchymal intratubular crystals and kidney stone-related gene and protein expression levels were examined in noncancerous renal sections from both groups. Results SFs had a higher smoking rate (P = 0.0097); lower red blood cell, hemoglobin, and hematocrit values; and higher urinary red blood cell, white blood cell, and bacterial counts than NSFs. Scanning electron microscopy revealed calcium-containing crystal deposits and crystal attachment to the renal tubular lumen in both groups. Both groups demonstrated crystal transmigration from the tubular lumen to the interstitium. The crystal diffusion analysis indicated a significantly higher crystal existing ratio in the medulla and papilla of SFs and a significantly higher number of papillary crystal deposits in SFs than NSFs. The expression analysis indicated relatively high osteopontin and CD68, low superoxide dismutase, and significantly lower Tamm–Horsfall protein expression levels in SFs. Multivariate logistic regression analysis involving the above factors found the presence of renal papillary crystals as a significant independent factor related to SFs (odds ratio 5.55, 95% confidence interval 1.08–37.18, P = 0.0395). Conclusions Regardless of stone formation, intratubular crystals in the renal parenchyma seem to transmigrate to the interstitium. SFs may have reduced ability to eliminate renal parenchymal crystals, particularly those in the papilla region, than NSFs with associated gene expression profiles