Phagocytosis model of calcium oxalate monohydrate crystals generated using human induced pluripotent stem cell-derived macrophages.

Macrophages play a role in nephrolithiasis, offering the possibility of developing macrophage-mediated preventive therapies. To establish a system for screening drugs that could prevent the formation of kidney stones, we aimed to develop a model using human induced pluripotent stem cell (iPSC)-derived macrophages to study phagocytosis of calcium oxalate monohydrate (COM) crystals. Human iPSCs (201B7) were cultured. CD14+ monocytes were recovered using a stepwise process that involved the use of growth factors and cytokines. These cells were then allowed to differentiate into M1 and M2 macrophages. The macrophages were co-cultured with COM crystals and used in the phagocytosis experiments. Live cell imaging and polarized light observation via super-resolution microscopy were used to visualize phagocytosis. Localization of phagocytosed COM crystals was observed using transmission electron microscopy. Intracellular fluorescence intensity was measured using imaging cytometry to quantify phagocytosis. Human iPSCs successfully differentiated into M1 and M2 macrophages. M1 macrophages adhered to the culture plate and moved COM crystals from the periphery to cell center over time, whereas M2 macrophages did not adhere to the culture plate and actively phagocytosed the surrounding COM crystals. Fluorescence assessment over a 24-h period showed that M2 macrophages exhibited higher intracellular fluorescence intensity (5.65-times higher than that of M1 macrophages at 4.5 h) and maintained this advantage for 18 h. This study revealed that human iPSC-derived macrophages have the ability to phagocytose COM crystals, presenting a new approach for studying urinary stone formation and highlighting the potential of iPSC-derived macrophages as a tool to screen nephrolithiasis-related drugs.

Three-dimensional computed tomography-based resection process map for robot-assisted partial nephrectomy: propensity score matching of a single-center retrospective study.

BACKGROUND AND OBJECTIVES: We aimed to examine the effect of preoperative three-dimensional (3D) computed tomography (CT)-based resection process map (RPM) imaging on the outcomes of robot-assisted partial nephrectomy (RAPN). METHODS: We retrospectively analyzed 177 patients (RPM group, n = 92; non-RPM group, n = 85) who underwent this surgery between November 2012 and April 2022. Patient-specific contrast-enhanced CT images were used to construct an RPM, a 3D representation of the kidney showing the planned tumor resection and a 5 mm safety margin. Outcome analyses were performed using propensity score matching. The primary endpoint was the trifecta achievement rate. RESULTS: We extracted 90 cases. The trifecta achievement rate showed no significant differences between the RPM (73.3%) and non-RPM groups (73.3%). However, the RPM group had fewer Grade 3 and higher complications (0.0% vs. 13.3%, p = 0.026). The da Vinci Xi (OR 3.38, p = 0.016) and tumor diameter (OR 0.95, p = 0.013) were independent factors affecting trifecta achievement in multivariate analysis. Using RPM imaging was associated with the absence of Grade 3 and higher perioperative complications (OR 5.33, p = 0.036) in univariate analysis. CONCLUSIONS: Using preoperative 3D CT-based RPM images before RAPN may not affect trifecta achievement, but may reduce serious complication occurrence by providing detailed information on tumor resection.

Comparison of Percutaneous Renal Access Between Robot-Assisted Fluoroscopy Guidance Using the Bi-Plane Method and Ultrasound Guidance: A Multicenter Randomized Control Benchtop Study.

Purpose: To evaluate the efficacy of supine percutaneous renal access by robot-assisted (RA) fluoroscopy and ultrasound (US) guidance in terms of procedural outcomes and surgeon workload. Methods: We conducted a multicenter, randomized, controlled benchtop study involving 32 urologists using a renal phantom model. RA puncture was performed using the developed version of automated needle targeting with X-ray (ANT-X), which determines the direction of the needle. US puncture was performed under US guidance. The primary endpoint was the single-puncture success rate, and the secondary outcomes were the procedural time for each step, time of fluoroscopic exposure, and workload assessment. Results: The single-puncture success rates were 90.6% and 56.3% for RA and US punctures, respectively (p < 0.01). In RA puncture, the median device setup time was 120 seconds longer, the median total procedural time was 100 seconds longer, the median time of fluoroscopic exposure was 40 seconds longer, the median needle puncture time was 17 seconds shorter, and the distance from the target sphere was 1 cm shorter than those in US puncture (all p < 0.01). The mental and physical task workload, effort required by the surgeons, frustration felt by the surgeons, and overall National Aeronautics and Space Administration Task Load Index scores were lower in the RA puncture group than in the US puncture group (p = 0.01, p = 0.046, p < 0.01, p = 0.021, and p ≤ 0.01, respectively). Conclusions: RA puncture using ANT-X, which can also be used for puncture in the supine position, offers advantages over renal puncture in terms of accuracy and surgical workload.

Clinical and postoperative characteristics of stentless ureteroscopy patients: a prospective analysis from ReSKU.

INTRODUCTION: To evaluate the clinical characteristics as well as the postoperative course of urolithiasis patients undergoing a ureteroscopy (URS) without stent placement. MATERIALS AND METHODS: This was a prospective case cohort study utilizing data collected in the Registry for Stones of the Kidney and Ureter (ReSKU) from a single institution between October 2015 and December 2020. We identified all consecutive patients undergoing URS for stone disease and analyzed data encompassing demographics, medical history, intra and postoperative characteristics, including complications and postoperative symptoms. Univariate and multivariate logistic regression analyses were performed based on the presence or absence of an indwelling ureteral stent. RESULTS: A total of 470 patients were included for analysis, 92 patients in the stentless group (19.5%). Factors associated with stentless ureteroscopy were a lower stone burden (p < 0.001), the pre-existence of a ureteral stent (37.4% vs. 27.9% p = 0.011), absence of an access sheath (14.6% vs. 69.5% p < 0.001), and a shorter operative time (31 vs. 58 min p < 0.001). Postoperative gross hematuria and lower urinary tract symptoms (LUTS) were reported less frequently in stentless patients (p = 0.02, p = 0.01, respectively). There was no difference in postoperative complications between both groups (15.2% vs. 12.0%, p = 0.385). On multivariate analysis, the risk of postoperative complications was associated with obesity, stone burden ≥ 1 cm, and positive preoperative urine culture. There was no patient who required emergent stent placement in the stentless group. CONCLUSION: Our data show that, in well selected patients, omitting ureteral stent placement after URS can decrease postoperative gross hematuria and LUTS without increasing postoperative complications.

Ultrasound-Only Percutaneous Nephrolithotomy Is Safe and Effective Compared to Fluoroscopy-Directed Percutaneous Nephrolithotomy.

Introduction: Outcomes after ultrasound-only percutaneous nephrolithotomy (PCNL), in which no fluoroscopy is used, are not well known. The goal of this study was to compare outcomes of ultrasound-only and fluoroscopy-directed PCNL. Materials and Methods: Prospectively collected data from the Registry for Stones of the Kidney and Ureter database were reviewed for all patients who underwent PCNL at one academic center from 2015 to 2021. Primary outcomes were complications and stone-free rates (no residual fragments ≥3 mm). Results: Of the 141 patients who underwent ultrasound-only PCNL and 147 who underwent fluoroscopy-directed PCNL, there was no difference in complication rates (15% vs 16%, p = 0.87) or stone-free status (71% vs 65%, p = 0.72), respectively. After adjusting for body mass index, American Society of Anesthesiologists (ASA), stone size, and stone complexity by Guy score, ultrasound-only PCNL was not associated with any increased odds of complications (odds ratio [OR] 0.7, 95% confidence interval [CI] 0.3-1.6, p = 0.41) or residual stone fragments ≥3 mm (OR 1.0, 95% CI 0.5-1.9, p = 0.972) compared with fluoroscopy-directed PCNL. Ultrasound-only PCNL was associated with shorter operative time (median 99.5 vs 126 minutes, p < 0.001), and the use of ultrasound remained a significant predictor of short operative time (<100 minutes) after controlling for supine positioning, stone size, and stone complexity by Guy score (OR 2.31, 95% CI 1.01-5.29, p = 0.048). Patients in the ultrasound-only group were spared a mean radiation exposure dose of 10 mGy per procedure. Conclusions: Ultrasound-only PCNL is safe and achieves similar stone-free rates compared with fluoroscopy-directed PCNL with the added benefit of avoidance of radiation.

Single-Use Ureteroscopes Are Associated with Decreased Risk of Urinary Tract Infection After Ureteroscopy for Urolithiasis Compared to Reusable Ureteroscopes.

Objective: Urinary tract infection (UTI) is a common complication after ureteroscopy. Despite sterilization, there is evidence that reusable ureteroscopes can still harbor bacteria. Whether this property is associated with increased risk of UTI is unknown. The objective of this study was to compare rates of postoperative UTI after ureteroscopy for urolithiasis performed with single-use ureteroscopes vs reusable ureteroscopes. Materials and Methods: This was a single-center, retrospective cohort study of all patients who underwent ureteroscopy for urolithiasis between June 2012 and March 2021. Outcomes were compared between those who underwent stone removal with single-use and reusable ureteroscopes. The primary endpoint was postoperative UTI. The secondary endpoints were intra-operative and postoperative outcomes, and health service utilization after surgery. Results: Of 991 patients identified, 500 (50.4%) underwent ureteroscopy with a single-use ureteroscope. Rates of postoperative UTI were lower in those undergoing ureteroscopic stone removal with a single-use ureteroscope compared to a reusable ureteroscope (6.5% vs 11.9%, p = 0.018). In multivariable analysis, use of a single-use ureteroscope was associated with lower odds of postoperative UTI compared to a reusable ureteroscope when adjusting for risk (odds ratio 0.37, p = 0.015). Use of a single-use ureteroscope was associated with a higher stone clearance rate compared to a reusable ureteroscope (90.0% vs 83.9%, p = 0.005). There was no difference in operative time, overall complication rate, readmission, or emergency department visits between two groups. Conclusion: Single-use ureteroscopes are associated with a twofold decreased risk of UTI and increased stone clearance rate after ureteroscopy for urolithiasis compared to reusable ureteroscopes.

A Multicenter, Prospective, Non-randomized Study Evaluating Surgical hand Preparation between Double-Gloving and Single-Gloving for Preventing Postoperative Infection in Robotic and Laparoscopic Minimally Invasive Surgeries.

PURPOSE: This study aimed to analyze a feasible and suitable surgical precautionary preparatory technique. The techniques of double-gloving with hygienic hand wash (DH) and single-gloving with surgical hand wash (SS) were compared for their ability to prevent postoperative infection in robotic and laparoscopic minimally invasive surgeries. MATERIALS AND METHODS: A prospective, non-randomized, multicenter study was conducted between January 2016 and June 2020. We divided the robotic and laparoscopic cases into two groups: DH and SS. Data on infectious outcomes were collected. Propensity score matching was performed to control for operative characteristics between the two groups. The primary endpoint was the presence of fever and surgical site infections (SSIs) indicating postoperative infection. RESULTS: Among four medical centers, seven surgeons were allocated to either the DH or the SS group. A total of 221 and 251 patients underwent DH and SS, respectively. Propensity score matching, which included 171 cases from each group, showed that the incidence of fever during hospitalization was significantly lower in the DH group than that in the SS group (11.7% vs. 23.4%, p=0.007). Multivariable analysis revealed that DH was associated with a reduced odds ratio for developing postoperative fever during hospitalization (risk ratio: 0.49, p=0.043). No differences were found in SSI before and after hospitalization between the two groups. CONCLUSION: DH resulted in less postoperative fever and had a comparable effect in preventing SSIs. This procedure could be an alternative to the SS protocol in some minimally invasive surgeries.

Microdamage analysis of single-use flexible ureteroscope immediately after lithotripsy use.

This prospective ex vivo study investigated microdamage to single-use flexible ureteroscopes (fURS) after ureteroscopy and endoscopic combined intrarenal surgery (ECIRS). The performance of 30 WiScope devices (OTU Medical, San Jose, CA, USA) was examined immediately after use, dividing them into three equal groups: ureteroscopy and ECIRS in the prone and supine positions. The overall scope of microdamage assessment included the scope deflection, bending radius, resolution, and water flow rate. Additionally, we analyzed the association between scope status and surgical parameters. The deflection, bending radius, and resolution remained similarly above the thresholds in all groups. However, the water flow rate was below the threshold in seven scopes (70%) in the ureteroscopy group and none in the ECIRS groups (P = 0.001). Univariate and multivariable logistic regression analyses demonstrated that basket wire catheter use was associated with an increased risk for overall scope microdamage (odds ratio [OR], 22.70; P = 0.006 and OR, 22.40; P = 0.019, respectively). Stone size, total laser energy, and surgical position were not associated with a risk for scope microdamage. In conclusion, ureteroscopy was more closely associated with scope damage than ECIRS, and basket wire catheter use seemed to inflict more damage to the fURS.

A Randomized, Single-Blind Clinical Trial Comparing Robotic-Assisted Fluoroscopic-Guided with Ultrasound-Guided Renal Access for Percutaneous Nephrolithotomy.

PURPOSE: We conducted a randomized, single-blind clinical trial comparing the surgical outcomes of robotic-assisted fluoroscopic-guided (RAF group) and ultrasound-guided (US group) renal access in mini-percutaneous nephrolithotomy (PCNL). MATERIALS AND METHODS: We recruited patients who underwent mini-PCNL with ureteroscopic assistance for large renal stones between January 2020 and May 2021. Block randomization was performed using online software. Automated needle target with x-ray was used for fluoroscopic-guided renal access in the RAF group. PCNL was performed by residents using a pneumatic lithotripsy system with 16.5Fr/17.5Fr tracts. The primary outcome was single puncture success, and the secondary outcomes were stone-free rate, complication rate, parameters measured during renal access and fluoroscopy time. RESULTS: In total, 71 patients (35 in US group, 36 in RAF group) were enrolled. No difference was seen in the single puncture success rate between the US and RAF groups (34.3% and 50.0%, p=0.2). In 14.3% cases in the US group vs no cases in the RAF group, the resident was unable to obtain access due to difficult targeting (p=0.025). The mean number of needle punctures was significantly fewer, and the median duration of needle puncture was shorter in the RAF group (1.83 vs 2.51 times, p=0.025; 5.5 vs 8.0 minutes, p=0.049, respectively). The stone-free rate at 3 months after surgery was 83.3% and 70.6% in the RAF and US groups, respectively (p=0.26). Multivariate analysis revealed that RAF guidance reduced the mean number of needle punctures by 0.73 times (p=0.021). CONCLUSIONS: RAF renal access in mini-PCNL may have further potential applications in this field.

Risk Factors for Failure of Endoscopic Management of Stone-related Ureteral Strictures.

PURPOSE: To investigate factors determining the outcomes of endoscopic management for stone-related ureteral stricture. MATERIALS AND METHODS: Data of patients who underwent endoscopic surgery for ureteral stricture due to stones from January 2016 to April 2020 were retrospectively analyzed. We compared cases successfully treated with endoscopic surgery with cases that resulted in failure. We focused on factors associated with treatment success, including cause and length of stricture, methods of stricture treatment, surgical time, and duration of hydronephrosis before the treatment. Treatment success was defined as improvement in hydronephrosis status. RESULTS: Nineteen patients were treated for stone-related ureteral stricture. Hydronephrosis was successfully improved in 12 patients (63.2%). Seven patients with failed endoscopic management had ureteroscopic lithotripsy- related stricture, whereas 3/12 (25.0%) patients with ureteroscopic lithotripsy-related stricture and 7/12 (58.3%) patients with impacted stone-related stricture were successfully treated by endoscopic management (P = .004). The prevalence of stricture length > 15 mm was significantly higher in the patients with failed management than in the patients with successful management (71.4 vs 16.6%, P = .046). Intraoperative endoscopic observation demonstrated that the mucosa of the ureteroscopic lithotripsy-related stricture had ischemic appearance with relatively long stricture length (P = 0.13) compared to the impacted stone-related stricture. No association was observed between treatment outcome and method of endoscopic management, including laser incision, balloon dilation, or both. CONCLUSION: Ureteroscopic lithotripsy as a cause and stricture length > 15 mm could affect the success rate of endoscopic management of ureteral stricture. In such cases, reconstructive management should probably be considered in the early stages.

Macrophage Function in Calcium Oxalate Kidney Stone Formation: A Systematic Review of Literature.

Background: The global prevalence and recurrence rate of kidney stones is very high. Recent studies of Randall plaques and urinary components in vivo, and in vitro including gene manipulation, have attempted to reveal the pathogenesis of kidney stones. However, the evidence remains insufficient to facilitate the development of novel curative therapies. The involvement of renal and peripheral macrophages in inflammatory processes offers promise that might lead to the development of therapeutic targets. The present systematic literature review aimed to determine current consensus about the functions of macrophages in renal crystal development and suppression, and to synthesize evidence to provide a basis for future immunotherapy. Methods: We systematically reviewed the literature during February 2021 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles investigating the relationship between macrophages and urolithiasis, particularly calcium oxalate (CaOx) stones, were extracted from PubMed, MEDLINE, Embase, and Scopus. Study subjects, languages, and publication dates were unrestricted. Two authors searched and screened the publications. Results: Although several studies have applied mixed modalities, we selected 10, 12, and seven (total, n = 29) of 380 articles that respectively described cultured cells, animal models, and human samples.The investigative trend has shifted to macrophage phenotypes and signaling pathways, including micro (m)-RNAs since the discovery of macrophage involvement in kidney stones in 1999. Earlier studies of mice-associated macrophages with the acceleration and suppression of renal crystal formation. Later studies found that pro-inflammatory M1- and anti-inflammatory M2-macrophages are involved. Studies of human-derived and other macrophages in vitro and ex vivo showed that M2-macrophages (stimulated by CSF-1, IL-4, and IL-13) can phagocytose CaOx crystals, which suppresses stone development. The signaling mechanisms that promote M2-like macrophage polarization toward CaOx nephrocalcinosis, include the NLRP3, PPARγ-miR-23-Irf1/Pknox1, miR-93-TLR4/IRF1, and miR-185-5p/CSF1 pathways.Proteomic findings have indicated that patients who form kidney stones mainly express M1-like macrophage-related proteins, which might be due to CaOx stimulation of the macrophage exosomal pathway. Conclusions: This systematic review provides an update regarding the current status of macrophage involvement in CaOx nephrolithiasis. Targeting M2-like macrophage function might offer a therapeutic strategy with which to prevent stones via crystal phagocytosis.

A novel approach in creating nephrostomy using a double-lumen access sheath during endoscopic combined intrarenal surgery.

BACKGROUND: This study aimed to evaluate the safety and efficacy of an inner ureteral access sheath (i-UAS) with a double-lumen channel used in ureteroscopic lithotripsy (URS) as a dilator for the percutaneous tract in endoscopic combined intrarenal surgery (ECIRS). METHODS: This was a single-center cohort study conducted from January 2016 to April 2020. We used an i-UAS as a dilator and a double-lumen catheter to insert a safety guidewire during the creation of the nephrostomy tract in ECIRS. Univariate and multivariate analyses were performed to assess the association between the perioperative parameters and the use of i-UAS. The primary endpoint was perioperative complications, and secondary endpoints were stone-free rate (SFR), operative time, fluoroscopy time, and duration of hospitalization. RESULTS: In total, 221 patients were enrolled during the study period. Patients were divided into an i-UAS dilation group (n=108) and a one-shot dilation group (n=113). No differences were observed between the two groups in terms of patient history. Univariate analyses indicated that, in the i-UAS dilation group, the operative time was shorter [105.50 (83.75-143.25) vs. 121.00 (90.00-155.00) min; P=0.02] and the modified Valdivia position was more frequently selected. Multivariate analyses showed no significant differences in the frequency of complications, such as urinary injury or postoperative pyelonephritis, but it showed a significantly shorter operative time as well as fewer tract creation troubles in the i-UAS dilation group. CONCLUSIONS: Using an i-UAS as a dilator and a double-lumen catheter to insert a safety guidewire during ECIRS is a convenient and safe technical method for creating a nephrostomy tract that can reduce the operative time.

Surgical hand hygiene and febrile urinary tract infections in endourological surgery: a single-centre prospective cohort study.

Surgical hand hygiene reduces the risk of surgical site infections (SSIs). SSIs are not considered an issue in endourological surgery, whereas febrile urinary tract infections (f-UTIs) and urological sepsis are becoming problematic. We wondered whether surgical hand hygiene is necessary for endourological surgery. Therefore, we aimed to evaluate the influence of surgical hand hygiene on f-UTI onset in endourological surgery by comparing procedures in which surgical hand hygiene with double gloving was used with those in which regular hand hygiene with double gloving was used between April 2016 and July 2020. In this prospective cohort study of 477 patients who underwent endourological surgeries, surgeons in the surgical hand hygiene and regular hygiene groups performed surgery on 259 and 218 patients, respectively. There was no significant difference in patient background, and multivariate analyses revealed no significant differences in f-UTI onset (odds ratio, 0.87; p = 0.74) between the two groups. In conclusion, regular hand hygiene with double gloving may be considered an alternative to surgical hand hygiene to prevent endourological f-UTIs, which could alter operational protocols for endourological surgery. Further studies are needed to validate our findings.

Prospective evaluation and classification of endoscopic findings for ureteral calculi.

Difficulty in performing ureteroscopic lithotripsy (URSL) depends on endoscopic findings surrounding calculi. In this multicentre prospective cohort study of 185 patients with a single ureteral stone who underwent ureteroscopic lithotripsy registered in the SMART study between January 2014 and February 2017, we established a classification of endoscopic findings and analysed risk factors for ureteral changes. We evaluated endoscopic findings (oedema, polyps, ureteral mucosa-stone adherence, and distal ureteric tightness) based on the SMART classification. Operative time and ureteral injuries were significantly correlated with endoscopic finding grades. Multivariate analyses revealed that mucosa-stone adherence (MSA) was strongly affected by hydronephrosis grade (odds ratio, 12.4; p = 0.022) and the interval before surgery (odds ratio, 1.10; p = 0.012). The cutoff value for MSA was 98 days, with a predictive accuracy of 0.78. Risk factors for distal ureteric tightness were age (odds ratio, 0.96; p = 0.004) and early intervention (odds ratio, 0.90; p = 0.023). The cutoff value was 34 days, with a predictive accuracy of 0.72. In conclusion, appropriate intervention around 34 days (limited to 98 days) after symptom onset is necessary for treating ureteral calculi. Even if intervention passed 98 days post-symptom onset, staged URSL, alternative procedures, and detailed informed consent should be planned in advance, assuming strong MSA.

Deregulated MTOR (mechanistic target of rapamycin kinase) is responsible for autophagy defects exacerbating kidney stone development.

Kidney stone disease is a lifestyle-related disease prevalent in developed countries; however, effective medical treatment for the disease is not yet well established. As cellular damage in renal tubular cells (RTCs) is responsible for the disease, here, we focused on the role of macroautophagy/autophagy in RTCs. We found that autophagic activity was significantly decreased in mouse RTCs exposed to calcium oxalate (CaOx) monohydrate crystals and in the kidneys of GFP-conjugated MAP1LC3B (microtubule- associated protein 1 light chain 3 beta) transgenic mice with CaOx nephrocalcinosis induced by glyoxylate. This caused accumulation of damaged intracellular organelles, such as mitochondria and lysosomes, the normal functioning of which is mediated by functional autophagy. An impairment of autophagy was also observed in the mucosa with plaques of CaOx kidney stone formers. We determined that the decrease in autophagy was caused by an upregulation of MTOR (mechanistic target of rapamycin kinase), which consequently resulted in the suppression of the upstream autophagy regulator TFEB (transcription factor EB). Furthermore, we showed that an MTOR inhibitor could recover a decrease in autophagy and alleviate crystal-cell interactions and the formation of crystals associated with increased inflammatory responses. Taken together, we conclude that autophagy compromised by MTOR deregulation is a fundamental feature in the pathology of kidney stone formation, and propose that chemical inhibition of MTOR could be a prospective strategy for disease suppression.Abbreviations: ACTB: actin, beta; CaOx: calcium oxalate; CKD: chronic kidney disease; COM: calcium oxalate monohydrate; LGALS3/galectin-3: lectin, galactose binding, soluble 3; GFP: green fluorescent protein; GOX: glyoxylate; HE: hematoxylin and eosin; MAPLC3B: microtubule- associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; NAC: N-acetyl-L-cysteine; ROS: reactive oxygen species; RTC: renal tubular cell; SQSTM1/p62: sequestosome 1; TFEB: transcription factor EB; TEM: transmission electron microscopy; tfLC3: tandem fluorescent-tagged LC3; 3-MA: 3-methyladenine.

Robot-Assisted Fluoroscopy Versus Ultrasound-Guided Renal Access for Nephrolithotomy: A Phantom Model Benchtop Study.

Objectives: To evaluate the feasibility of robot-assisted fluoroscopy-guided (RAG) puncture and to compare RAG puncture, utilizing a novel robot system for percutaneous renal access, with ultrasound-guided (USG) puncture. Materials and Methods: We conducted a benchtop study with a renal phantom model using the automated needle targeting with an X-ray system. Seventeen urologists participated in this study and performed RAG and USG phantom punctures. The number of needle punctures, device setup time, and fluoroscopic exposure duration were recorded for the analyses. Results: The single puncture success rates of the RAG and USG punctures were 100% and 70.6%, respectively (p = 0.021). The median needle puncture time of RAG puncture was 24% shorter than that of USG puncture (35.0 vs 46.0 seconds; p < 0.001), and the median device setup time of RAG puncture was a minute longer than that of USG puncture (93.0 vs 30.5 seconds; p < 0.001). The median duration of fluoroscopic exposure of RAG puncture was longer than that of USG puncture (38.0 vs 6.5 seconds; p < 0.001). The surgeon's self-assessment results demonstrated that the participating urologists found RAG puncture to be safer and have better visibility than USG puncture; they were also more satisfied with RAG puncture. Subanalysis revealed that, in the RAG group, the attending surgeons had shorter total procedural time than the residents (p = 0.045). Conclusion: RAG puncture showed comparable results and accuracy rates with USG puncture for renal access.

Active Phagocytosis and Diachronic Processing of Calcium Oxalate Monohydrate Crystals in an in vitro Macrophage Model.

BACKGROUND: We previously discovered that renal macrophages (Mφs) phagocytose renal calcium oxalate monohydrate (COM) crystals. This study investigated the processing of engulfed crystals using in vitro models. METHODS: J774.1 mouse Mφs were exposed to COM crystals and observed for 24 h using polarized light microscopy with/without cytochalasin B (CB), an inhibitor of phagocytosis, to confirm active crystal phagocytosis. LysoTracker and immunohistochemical staining using transmission electron microscopy for lysosomal-associated membrane protein 1 were used to confirm engulfed COM crystal uptake into lysosomes. Diachronic tracking of specific Mφs was performed to capture the entire course of engulfed COM crystal processing using polarized light microscopy. Follow-up studies of fluorescent COM (f-COM) crystals using imaging cytometry were performed in the presence and absence of nigericin to dissipate the pH gradient in acidic organelles. RESULTS: Phagocytosis rates increased with COM density and were significantly lower in cells treated with CB (p < 0.01). We observed that engulfed crystals colocalized within lysosomes of the Mφs; moreover, diachronic observation indicated that the engulfed COM crystals were subdivided during Mφ division and eliminated by the 7th day of culture. Additionally, imaging cytometry showed that the fluorescence level of f-COM crystals in the nigericin (-) group after 48 h was significantly lower than that in the nigericin (+) group. CONCLUSIONS: This study confirmed active phagocytosis and lysosomal processing of engulfed COM crystals by Mφs. This discovery is expected to contribute to the development of future drugs that enhance the COM crystal phagocytic ability of Mφs.

Brown adipocytes and ß3-stimulant-induced brown-like adipocytes contribute to the prevention of renal crystal formation.

According to recent studies, kidney stones are associated with metabolic syndrome. We focused on brown adipocytes and ß3-stimulant-induced brown-like adipocytes to investigate how these adipocytes influence kidney stone disease. For the interscapular brown adipose tissue (iBAT) removal experiment, mice were subjected to either iBAT removal or sham operation (X-BAT group or sham group), and, after 3 wk, renal crystal deposition was induced by intra-abdominal injection of glyoxylate (GOX) for 6 days. For the ß3-stimulant experiment, mice were administered intra-abdominal injections of the ß3-stimulant (ß3-group) or saline (control group) for 6 days. Thereafter, renal crystal deposition was induced by intra-abdominal injection of GOX for 6 days. iBAT removal decreased the expression of Sod1 and increased that of chemokine (C-C motif) ligand 2 (Ccl2), EGF module-containing mucin-like receptor 1 (Emr1), and tumor necrosis factor (Tnf) in the kidneys. Renal crystal deposition was 2.06-fold higher in the X-BAT group than in the sham group. The ß3-stimulant caused differentiation of white adipocytes into brown-like adipocytes. In the kidneys of the ß3-group, the expression of Ccl2 and Emr1 decreased and that of Sod1 increased. Renal crystal deposition was 0.17-fold lower in the ß3-group than in the control group. In summary, iBAT removal promoted kidney inflammation and renal crystal formation. ß3-Stimulant-induced brown-like adipocytes reduced inflammation and improved antioxidant action in the kidneys, which suppressed renal crystal formation. This is the first report on the therapeutic role of brown and brown-like adipocytes for kidney stone formation.

Complete surgical removal of multiple tumor lesions in malignant pheochromocytomas produces a good prognosis.

INTRODUCTION: Malignant pheochromocytomas are rare catecholamine secreting tumors; there is no definitive strategy for the treatment of malignant pheochromocytomas, especially in cases with multiple tumors. CASE PRESENTATION: A 72-year-old woman with diabetic ketoacidosis presented with multiple malignant pheochromocytomas 16 years after undergoing adrenalectomy. After three courses of systemic chemotherapy, there was no change in the size of tumor lesions or serum catecholamine levels; surgical removal of all lesions was carried out. Eighteen months after the operation, the patient has had no recurrences and her diabetes is controlled well by oral medication. CONCLUSION: Our findings indicate that complete surgical resection should be considered, even in patients with multiple malignant pheochromocytomas.