Defining a learning curve for urology trainees to achieve renal access without complications in endoscopic combined intrarenal surgery.

OBJECTIVES: There is a lack of data on the number of surgeries required for endoscopic combined intrarenal surgery (ECIRS). Accordingly, we aimed to identify the learning curve for ECIRS performed by multiple surgeons. METHODS: We included 296 patients who underwent ECIRS at our university hospital between 2016 and 2021. A learning curve for percutaneous nephrolithotomy side was calculated considering urology-resident surgeons. The learning curve was retrospectively analyzed for surgical time, renal puncture time, stone-free rate, and complications and corrected for age, body mass index, stone size, computed tomography value, cumulative number of surgeries, and stone location. RESULTS: This study included cases performed by 32 surgeons, including 30 residents and 2 attending surgeons. The median number of surgeries performed by the residents and attending surgeons prior to this study was 4.5 and 90, respectively. The median number of surgical procedures performed during the training period was seven. The surgical time of the residents decreased as the number of cases increased, reaching a median surgical time of 111 min for the attending surgeons after 16.4 cases. Renal puncture time was achieved in 20.1 cases. Complications related to renal access were observed in 13.0% (34 patients), Clavien-Dindo grade II in 1.9% (5 patients), and grade III or higher in 0.8% (2 patients). Comparing the first to fifth cases with the 21st and subsequent cases, the complication rate improved from 35% to 13%. CONCLUSION: Our study demonstrated that ECIRS training provided 16-20 cases with a learning curve to achieve acceptable surgical outcomes.

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.

Impact of pelvicalyceal anatomical variation on surgical outcomes of endoscopic combined intrarenal surgery.

Objectives: The objective of this work is to investigate the impact of the pelvicalyceal anatomical system (PCS) on calyceal stone formation and surgical outcomes of endoscopic combined intrarenal surgery (ECIRS) for renal and/or proximal ureteral stones with a diameter >15 mm. Patients and methods: PCS was classified as Type I (single pelvis) or Type II (divided pelvis) according to the simple anatomical Takazawa classification. Using prospectively collected data from January 2016 to April 2020, 219 patients were retrospectively reviewed. After excluding patients who underwent a staged procedure, had hydronephrosis greater than grade 2, prior nephrostomy tubes, and failed to access the renal collecting system, 115 patients (Type I: 81, Type II: 34) were included, and the distribution of calyceal stones and surgical outcomes in ECIRS were compared between Types I and II PCS. Results: The median number of renal stone calyces in the Type II group was significantly more than that in the Type I group (p = 0.016). In particular, the Type II group possessed more upper stone calyces. Multivariate logistic regression analysis revealed that Type II PCS was associated with an increased odds ratio (OR) for the presence of upper stone calyces (OR: 2.93, p = 0.018). The stone-free (SF) status at 1 month after surgery, confirmed by abdominal plain radiography, was significantly higher in the Type I group compared with that in Type II (67.9% vs. 39.4%, respectively; p = 0.006). The requirement for additional surgical interventions was significantly higher in the Type II group compared with that in Type I (35.4% vs. 7.4%, respectively; p < 0.001). Multivariate analysis revealed that the number of stone calyces (OR: 4.26; p = 0.001) and Type II PCS (OR: 3.43; p = 0.009) were independent predictors of residual stones after ECIRS. Conclusion: We first revealed that the anatomic properties of PCS play a role in both upper calyceal stone formation and in the success of the ECIRS procedure. Because the SF rate in Type II PCS was significantly lower than that in Type I PCS, additional percutaneous nephrolithotomy tracts might be required, even for ECIRS.

A rare case of a clear cell carcinoma in a female urethral diverticulum.

Introduction: Urethral clear cell carcinoma is rare and often arises from a urethral diverticulum and rarely from the Müllerian duct. However, an explanation for this correlation remains unknown. Case presentation: We report the case of a 46-year-old woman who presented with hypermenorrhea. Magnetic resonance imaging revealed a papillary tumor in a cystic lesion in the dorsal urethra. We performed a robot-assisted radical cystourethrectomy and created an ileal conduit. Since pathological findings revealed microvascular and lymphovascular invasions around the urethra, adjuvant radiation therapy was administered. The patient showed no signs of recurrence or metastasis after treatment. Conclusion: We report a case of clear cell carcinoma in a female urethral diverticulum originating from a Müllerian duct cyst. While postoperative radiation therapy has been shown to produce a good outcome in carcinoma cases similar to this one, we recommend that a radical cystourethrectomy be performed.

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.

Plasmacytoid Urothelial Carcinoma of the Bladder That Manifests Disseminated Carcinomatosis of the Bone Marrow: A Case Report of Extremely Rapid Progression.

Plasmacytoid urothelial carcinoma (PUC) of the bladder is a rare variant of invasive urothelial carcinoma (UC) with aggressive behavior. Despite its prognosis being poorer than that of conventional UC, a median overall survival of approximately 2 years is ensured when it is treated with radical cystectomy (RC), and few patients die within a few months of RC. In this paper, we report the case of a patient with PUC who developed widespread bone metastasis only 6 weeks after RC, which resulted in death within 2 months postoperatively.

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.

Comparison of drug susceptibility between Escherichia coli detected in stool cultures of patients undergoing transrectal prostate needle biopsy and Escherichia coli in hospital-wide urine antibiograms.

A prostate biopsy is essential for prostate cancer diagnosis. However, infections are one of the biopsy-associated complications, and post-biopsy fever is estimated to occur in approximately 1% of all cases. It may thus be beneficial to perform a rectal swab culture before a transrectal prostate biopsy to confirm the presence of resistant bacteria and select preventive antibacterial agents according to the drug susceptibility results. This study aimed to determine whether there is a difference between the drug susceptibility of bacteria detected in the stool of patients who were scheduled to undergo prostate biopsy and the hospital-wide urine antibiogram. Patients suspected of having prostate cancer who underwent transrectal prostate biopsy via transrectal ultrasonography between August 1, 2016, and June 30, 2020, were included in this study. Stool samples were collected and cultured before biopsy. Overall, 99 patients underwent prostate biopsy, and of these, culture results were available for 81 patients (81.8%). Escherichia coli was detected in 74.0% (60 samples) of the stool culture samples, of which 4 samples were extended-spectrum ß-lactamase-producing types. We found greater susceptibility of Escherichia coli to ampicillin, fluoroquinolones, sulfamethoxazole/trimethoprim, and cefixime in the stool culture antibiogram than in the hospital-wide urine antibiogram. We also found a significantly low incidence of ESBL-positive Escherichia coli in the stool culture antibiogram with p-values of 0.009, 0.007, and 0.03 compared to the hospital-wide urine antibiograms for 2017, 2018, and 2019, respectively. Stool culture of prostate cancer patients undergoing biopsy may provide useful information for selecting prophylactic antimicrobial agents.

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.

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.

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.

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

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.

Complete remission of metastatic pheochromocytoma in 123I-metaiodobenzylguanidine scintigraphy after a single session of 131I-metaiodobenzylguanidine therapy: a case report.

BACKGROUND: Pheochromocytomas are rare neuroendocrine tumors, with a malignancy frequency of approximately 10%. The treatment of malignant pheochromocytoma is palliative, and the traditional management strategy has limited efficacy. Furthermore, no clear criteria exist for the treatment of metastatic pheochromocytoma, especially for unresectable lesions. We report a case of complete remission of metastatic pheochromocytoma in 123I-metaiodobenzylguanidine (MIBG) scintigraphy after a single session of 131I-MIBG therapy. CASE PRESENTATION: A 61-year-old woman had a right adrenal grand tumor and lymph node metastasis on the hilum of the right kidney, both of which incorporated MIBG. After surgery, immunostaining of a tumor specimen showed expression of the tumor makers chromogranin and synaptophysin. One year postoperatively, abdominal computed tomography revealed a local recurrence and retroperitoneal lymph node swelling. The local recurrence was positive for MIBG uptake, whereas the swollen retroperitoneal lymph nodes were negative. She underwent surgery again, but the local recurrence was unresectable because of rigid adhesion to the surrounding tissue. Immunostaining of an intraoperatively extracted swollen retroperitoneal lymph node showed expression of tumor markers. The patient then underwent a single session of 131I-MIBG therapy (7.4 GBq, 200 mCi), after which the residual lesions no longer incorporated MIBG, and a complete response in 123I- metaiodobenzylguanidine (MIBG) scintigraphy was achieved. The 131I-MIBG treatment was repeated 6 months later. None of the lesions were positive for MIBG uptake. CONCLUSIONS: 131I-MIBG therapy efficaciously treats unresectable lesions that are positive for MIBG uptake.