Avoiding "Needless" nephrectomy: What is the role of small renal mass biopsy in 2024?

Current guidelines do not mandate routine preoperative renal mass biopsy (RMB) for small renal masses (SRMs), which results in a considerable rate (18%-26%) of needless nephrectomy/partial nephrectomy for benign renal tumors. In light of this ongoing practice, a narrative review was conducted to examine the role of routine RMB for SRM. First, arguments justifying the current non-biopsy approach to SRM are critically reviewed and contested. Second, as a standalone procedure, RMB is critically assessed; RMB was found to have higher sensitivity, specificity, and an equal or lower complication rate when compared with other commonly preoperatively biopsied solid organ tumors (e.g., breast, prostate, lung, pancreas, thyroid, and liver). Based on the foregoing information, we propose a paradigm shift in SRM management, advocating for an updated policy in which partial nephrectomy or nephrectomy for SRM invariably occurs only after a preoperative biopsy confirms that a SRM is indeed malignant.

Single-Port vs Multiport Robot-Assisted Partial Nephrectomy: A Meta-Analysis.

Background: Several centers have reported their experience with single-port robot-assisted partial nephrectomy (SP-RAPN); however, it is uncertain if utilization of this platform represents an improvement in outcomes compared to multiport robot-assisted partial nephrectomy (MP-RAPN). To evaluate this, we performed a meta-analysis to compare the perioperative, oncological, and functional outcomes between SP-RAPN and MP-RAPN. Methods: For relevant articles, three electronic databases, including PubMed, Scopus, and Web of Science, were searched from their inception until January 1, 2023. A meta-analysis has been reported in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 and assessing the methodological quality of systematic reviews (AMSTAR) guidelines. The odds ratio (OR) and weighted mean difference (MD) were applied for the comparison of dichotomous and continuous variables with 95% confidence intervals (CI). Results: Of the 374 retrieved abstracts, 29 underwent full-text review, and 8 studies were included in the final analysis, comprising a total cohort of 1007 cases of RAPN (453 SP-RAPN cases and 554 MP-RAPN cases). Compared to MP-RAPN, the SP-RAPN group had a significantly longer ischemia time (MD = 4.6 minutes, 95% CI 2.8 to 6.3, p < 0.001), less estimated blood loss (MD = -12.4 mL, 95% CI -24.6 to -0.3, p = 0.045), higher blood transfusion rate (OR = 2.97, 95% CI 1.33 to 6.65, p = 0.008), and higher postoperative estimated glomerular filtration rate (eGFR) at 6 months (MD = 4.9 mL/min, 95% CI 0.2 to 9.7, p = 0.04). There was no significant difference in other outcomes between the two approaches, including the intraoperative complication, overall postoperative complication, minor postoperative complication (Clavien-Dindo I - II), major postoperative complication (Clavien-Dindo III-V), conversion to radical nephrectomy, pain score on day #1, pain score on discharge, morphine milligram equivalent usage, hospital stay, positive surgical margins, and postoperative eGFR. Conclusions: SP-RAPN represents an emerging technique using a novel platform. Initial studies have demonstrated that SP-RAPN is a safe and feasible approach to performing partial nephrectomy, although with inferior outcomes for ischemia time and blood transfusion rates. Further studies will be necessary to define the best usage of SP-RAPN within the surgeon's armamentarium.

Electromotive Drug Administration in the Porcine Renal Pelvis: First Report.

Introduction: Electromotive Drug Administration (EMDA) amplifies drug delivery deep into targeted tissues. We tested, for the first time, the ability of EMDA to deliver methylene blue into the urothelium of the renal pelvis. Materials and Methods: In an anesthetized female pig, both proximal ureters were transected two inches distal to the ureteropelvic junction. An 8F dual lumen catheter and a 5F fenestrated catheter with an indwelling silver wire were inserted into both renal pelvises following which methylene blue (0.1%) was infused at a rate of 5 mL/min for 20 minutes. In one pelvis, a 4 mA positive pulsed electrical current was applied to the silver wire. Results: In contrast to the control pelvis, the EMDA side macroscopically exhibited dense homogeneous staining; microscopy revealed penetration of methylene blue into the urothelium/lamina propria. Conclusion: In the porcine renal pelvis, application of EMDA increased the penetration of a charged molecule into the urothelium/lamina propria.

Assessing Decision Regret in Patients with Same-Day Discharge Pathway After Robot-Assisted Radical Prostatectomy.

Introduction: After the introduction of same-day discharge (SDD) pathways for various surgeries, these pathways have demonstrated comparable complication rates and a reduced overall cost of care. Outpatient robot-assisted radical prostatectomy (RARP) is introduced in high-volume centers; however, patients' perspectives on the SDD RARP protocol are not well understood. Materials and Methods: A questionnaire consisting of 24 questions, including the Likert Decisional Regret Scale, was distributed to patients who underwent RARP at our center. The overall decision regret score was calculated as described in the literature. We used 15 as a cutoff point for differentiating between high- and low-regret rates. Median and interquartile range were determined for non-normally distributed variables, while mean ± standard deviation was calculated for continuous data. Results: Of the 72 patients who completed the questionnaire, 65.7% (n = 44) of patients felt no regret about their decision of choosing the SDD RARP protocol and 90.3% (n = 65) of men stated that they would have made the same decision. At the same time, 97.1% (n = 68) of patients would also recommend this procedure to others. The median decisional regret score of the cohort (n = 67) was 0 (0-10). Fifty-four of 67 (80.6%) patients were in the low-regret score group, while 13 (19.4%) were in the high-regret group. Patients in the high-regret group were more likely to have low household income (<$30,000 a year) and they experienced postoperative pain more frequently compared with patients in the lower regret group (7.7% vs 1.9%, p = 0.626, and 61.5% vs 38.9%, p = 0.212, respectively). Conclusions: Most patients expressed low regret about choosing the SDD pathway for RARP, underscoring the importance of thorough explanation of the procedure and discharge process to enhance patient experience. However, a subset of patients did express regret, possibly due to an interplay of patient- and procedure-related factors.

Comparison of Ureteral Stent Biomaterials: Encrustation Profile in Lithogenic Artificial Urine Models.

Ureteral stent encrustation significantly limits indwelling time and can lead to downstream urological problems. However, no ideal polymeric biomaterials have been shown to completely resist encrustation in long-term urine exposure. Recently, 2-hydroxyethyl methacrylate (HEMA)-coated Pellethane was reported as a promising biomaterial resistant to encrustation. This study compared HEMA-coated Pellethane to commercially available stents under two different artificial urine environments. To evaluate the degree and composition of encrustation on HEMA-coated Pellethane, Boston Scientific Tria, Bard InLay Optima, Cook Universa Hydrogel, and Cook Black Silicone stents were used at various dwelling times in two different artificial urine environments. In a batch-flow model, samples of stents were suspended in an artificial urine solution (AUS) at 37 °C. Every 24 h for 11 weeks, 50% of the AUS would be replaced with fresh components using a programmable peristaltic pump system. The stent materials were removed at suitable time intervals and air-dried for 24 h under sterile conditions before follow-up analysis. SEM was used to assess the degree of encrustation, and inductively coupled plasma mass spectrometry (ICP-MS) was employed to quantify the encrusted compositions, specifically for calcium, magnesium, and phosphorus. We measured the weight gain over time due to encrusted deposits on the stents and quantified the amount of Ca, Mg, and P deposited on each encrusted stent. After the 11 week trial, HEMA-coated Pellethane showed the most average mass change. SEM showed that HEMA-coated Pellethane was fully encrusted in just 2 weeks in the AUS environments, and ICP-MS showed that Ca is the most abundant deposit. Among all the tested stents, Black Silicone performed the best. The two AUSs were formulated to encrust more rapidly than physiological conditions. HEMA-coated Pellethane is not an ideal stent material, while silicone is a promising material for advancing ureteral stents.

Evaluation of Renal Function and Stent Durability Following Resonance Stent Placement for Benign Disease.

Introduction: The metal-based Resonance stent (RS) has traditionally been placed in patients with malignant ureteral obstruction; as such, the long-term utility of RS among patients with benign ureteral obstruction (BUO) remains underinvestigated. Methods: We retrospectively reviewed our database for patients with BUO who underwent RS placement between 2010 and 2020. The impact of chronic RS placement on renal function was evaluated by estimated serum creatinine-based glomerular filtration rate (eGFR), furosemide renal scan, and CT-based renal parenchymal volume measurement. The number of and reason for RS stent exchanges during the follow-up period, incidence of encrustation, and the average indwell time were recorded. A cost analysis of placing the RS vs a polymeric stent was performed. Results: Among 43 RS patients with BUO, at a mean follow-up of 26 months, there was no change in eGFR (p = 0.99), parenchymal volume (p = 0.44), or split renal function of the stent-bearing side on renal scan (p = 0.48). The mean RS indwell time was 9.7 months. Eleven patients (26%) underwent premature stent replacement (6 cases) or removal (5 cases). Stents in 9 patients (32%) were encrusted, of which 4 (44%) required laser lithotripsy. Overall, 25 patients (58%) and 12 patients (28%) had a mean stent indwell time of ≥6 months and ≥12 months, respectively. Placing an RS resulted in a 52%, 37%, and 5.6% cost reduction compared with a regular polymeric stent placement, where it was exchanged every 6, 4, or 3 months, respectively. Conclusions: RS deployment in the patient with a BUO results in cost-effective maintenance of renal function and of renal parenchymal volume at a mean follow-up of 2 years; however, only 28% of patients fulfilled the 1-year criterion for RS indwell time.

A Review of the Recommendations and Strength of Evidence for Clinical Practice Guidelines on the Management of Small Renal Masses.

Introduction: With the rise in the detection of incidental small renal masses (SRM), the management paradigm for these patients has become an issue of increasing concern. We aim to identify areas of consensus, controversy, and opportunities for improvement among recently published guidelines and assess the strength of evidence for the management of SRMs. Methods: We reviewed practice guidelines for SRMs promulgated by the American Urological Association, European Association of Urology, National Comprehensive Cancer Network, American Society of Clinical Oncology, European Society for Medical Oncology, and the Chinese Society of Clinical Oncology. Levels of evidence and strength of recommendations for evaluation, management and follow-up were analyzed with regard to consensus, conflict, and neglect. Results: There is consensus among guidelines for the initial evaluation and treatment of SRMs; however, discrepancies exist with regard to indications for active surveillance, thermal ablation, and timing/method of follow-up after treatment. Routine renal mass biopsy is not recommended by any guideline. Overwhelmingly, guideline statements are based on low to moderate levels of evidence; only 23% of the reviewed guidelines were based on high-level evidence, 38% based on moderate-level, and 39% on low-level evidence or expert opinion. Conclusions: Despite all six guidelines sharing a consensus on most management topics regarding SRMs, the ongoing lack of high-level evidence precludes gold standard recommendations in the areas of diagnosis, treatment, and follow-up. More high-quality studies are needed to develop a stronger, data-supported universal guideline for the management of SRMs.

Electromotive Drug Administration in the Ureter in an In Vivo Animal Model: Initial Report.

Introduction: Electromotive drug administration (EMDA) delivers a drug deeply into targeted tissues, such as the bladder. EMDA has never been applied to the ureter. Methods: In four in vivo porcine ureters, a unique EMDA catheter containing a silver conducting wire was advanced for the infusion of methylene blue. In two ureters, a pulsed current was delivered through an EMDA machine, whereas the other two ureters served as a control. After 20 minutes of infusion, the ureters were harvested. Results: In the EMDA ureter, there was diffuse staining of the urothelium; penetration of methylene blue occurred in the lamina propria and muscularis propria. In the control ureter, there was only patchy staining of the urothelium. Conclusion: In this first report of ureteral EMDA, a charged molecule penetrated beyond the urothelium into the lamina propria and muscularis propria of the porcine ureter.

Single-Port Robotic Applications in Urology.

Objective: The da Vinci single-port (SP) platform represents the latest innovation in minimally invasive urologic surgery, and the adoption of this technology by urologists is increasing. In this article, we briefly describe the evolution of minimally invasive and single-site surgery, and offer a comprehensive review of the current literature on the SP platform. Materials and Methods: For relevant articles, three electronic databases, including PubMed, Scopus, and Web of Science, were searched from their inception until August 15, 2022. The published literature to date within SP robotic surgery in urology will be discussed. Evidence Synthesis: There are relatively few high-quality studies on the SP system, but there are multiple case series describing unique indications and surgical approaches with the SP robot, demonstrating safety and feasibility in the hands of experienced robotic surgeons. There also are an increasing number of prospective, larger cohort studies comparing outcomes between SP and multiport (MP) approaches that show benefits of the SP system regarding improved cosmesis, postoperative pain control, and decreased length of stay. Conclusions: Multiple prospective studies have shown benefits regarding cost and pain control for SP platform procedures compared to the traditional MP robotic approach. While its high cost and learning curve represent barriers to adoption, the SP platform represents a critical development in minimally invasive surgery. As this technology is further implemented at more institutions, long-term, high-quality data should accrue that will demonstrate its true value.

The Changing Role of Renal Mass Biopsy.

The incidence and prevalence of small renal masses (SRMs) continues to rise and with increased detection comes increases in surgical management, although the probability of an SRM being benign is upward of 30%. An extirpative treatment first diagnose-later strategy persists and clinical tools for risk stratification such as renal mass biopsy remain severely underutilized. The overtreatment of SRMs has multiple detrimental effects including surgical complications, psychosocial stress, financial loss, and reduced renal function leading to downstream effects such as the need for dialysis and cardiovascular disease.

Comparison of Superpulse Thulium Fiber Laser vs Holmium Laser for Ablation of Renal Calculi in an In Vivo Porcine Model.

Introduction and Objectives: We sought to compare the effectiveness and efficiency of the superpulse thulium fiber laser (sTFL to the holmium: yttrium-aluminum-garnet [Ho:YAG] laser for ureteroscopic "dusting" of implanted renal stones in an in vivo porcine model. Methods: Twenty-four porcine kidneys (12 juvenile female Yorkshire pigs) were randomized to Ho:YAG or sTFL treatment groups. Canine calcium oxalate stones were scanned with computed tomography to calculate stone volume and stone density; the stones were randomized and implanted into each renal pelvis via an open pyelotomy. In all trials, a 14F, 35 cm ureteral access sheath was placed. With a 9.9F dual lumen flexible ureteroscope, laser lithotripsy was performed using dusting settings: Ho:YAG 200 µm laser fiber at 16 W (0.4 J, 40 Hz) or sTFL 200 µm laser fiber at 16 W (0.2 J, 80 Hz). Lithotripsy continued until no fragments over 1 mm were observed. No stone basketing was performed. Throughout the procedures, intrarenal and renal pelvis temperatures were measured using two percutaneously positioned K-type thermocouples, one in the upper pole calyx and one in the renal pelvis. After the lithotripsy, the ureteropelvic junction was occluded, the kidneys were bivalved, and all residual fragments were collected, dried, weighed, and then measured with an optical laser particle sizer. Results: Implanted stones were similar in volume and density in both groups. Intraoperative collecting system temperatures were similar for both groups (all <44°C). Compared to Ho:YAG, sTFL ablated stones faster (9 vs 27 minutes, p < 0.001) with less energy expenditure (8 vs 26 kJ, p < 0.001), and a greater stone clearance rate (73% vs 45%, p = 0.001). After sTFL lithotripsy, 77% of the remaining fragments were ≤1 mm vs 17% of fragments ≤1 mm after Ho:YAG treatment (p < 0.001). Conclusions: In an in vivo porcine kidney, using dusting settings, sTFL lithotripsy resulted in shorter ablation times, higher stone clearance rates, and markedly smaller stone fragments than Ho:YAG lithotripsy.

Porcine Bladder Replacement with a Bilayer Silk Fibroin Enhanced Prosthetic Reservoir: A Feasibility Study.

Introduction: The creation of synthetic reservoirs for bladder replacement has been limited by challenges of interfacing synthetic materials and native tissue. We sought to overcome this challenge by utilizing a novel bilayer silk fibroin scaffold (BLSF) as an intermediary toward the development of an acellular prosthetic reservoir. Methods: Under institutionally approved protocols, 3D-printed reservoirs were implanted in six juvenile female pigs after cystectomy. BLSF was attached to the in situ prosthetic reservoir serving as an intermediary to native ureteral and urethral tissue anastomoses. Our first protocol allowed four pigs to be survived up to 7 days, and the second protocol allowed two pigs to be survived for up to 1 year. At the first sign of functional decline or the end of the study period, the animals were euthanized, and kidneys, ureters, prosthetic bladder, and urethra were harvested en bloc for histopathology analysis. Results: The first two pigs had anastomotic urine leaks because of design flaws resulting in early termination. The third pig had acute renal failure resulting in early termination. The artificial bladder design was modified in subsequent iterations. The fourth pig survived for 7 days and, upon autopsy, had intact urethral and ureteral anastomoses. The fifth and sixth pigs survived for 11 and 12 weeks, respectively, before they were sacrificed because of failure to thrive. One animal developed an enteric fistula. The other animal had an intact anastomosis, and the BLFS was identified at the ureteral and urethral anastomoses on histopathologic analysis. Conclusions: Replacing the porcine bladder with a prosthetic bladder was achieved for up to 3 months, the second longest survival period for a nonbiologic bladder alternative. BLSF was used for the first time to create an interface between synthetic material and biologic tissue by allowing ingrowth of urothelium onto the acellular alloplastic bladder.

Retrograde Cystonephroscopy for Complex Renal Calculi Using Novel Dual-Action Aspiration, Irrigation Cystoscope: Initial Case Series.

Introduction: Percutaneous nephrolithotomy is the gold standard treatment for kidney stones ≥2 cm; however, it remains an invasive procedure with significant risks especially in individuals with severe medical comorbidities. In contrast, while ureteroscopy is far less morbid, a major impediment to its use for larger calculi is the inability to evacuate the many fragments created during laser lithotripsy. Herein, we describe two patients with large-volume calculi and a third high-risk patient with a smaller stone who were treated with cystonephroscopy using a recently released, 16F flexible cystoscope equipped with dual aspiration and irrigation capabilities. Materials and Methods: Three consecutive female patients underwent retrograde cystonephroscopy from June 2021 to July 2021 with a novel 16F aspiration-enabled flexible cystoscope. Demographic data were collected. Preoperative and postoperative CT scan images were reviewed to determine linear stone dimensions and scalene ellipsoid volume. Results: The three female patients had an average age of 72.3 years and an American Society of Anesthesiologists (ASA) physical status score of 3. The mean preoperative stone volume was 4950 mm3. The average postcystonephroscopy stone volume was 217 mm3, resulting in a total stone clearance rate of 97%. No major complications occurred. The average procedure time was 176 minutes. Conclusions: Among the three high-risk female patients, two with large-volume calculi, retrograde cystonephroscopy with a novel aspiration-enabled cystoscope allowed for the procedure to be effectively completed solely via a retrograde approach.

Drosophila melanogaster as a function-based high-throughput screening model for antinephrolithiasis agents in kidney stone patients.

Kidney stone disease involves the aggregation of stone-forming salts consequent to solute supersaturation in urine. The development of novel therapeutic agents for this predominantly metabolic and biochemical disorder have been hampered by the lack of a practical pre-clinical model amenable to drug screening. Here, Drosophila melanogaster, an emerging model for kidney stone disease research, was adapted as a high-throughput functional drug screening platform independent of the multifactorial nature of mammalian nephrolithiasis. Through functional screening, the therapeutic potential of a novel compound commonly known as arbutin that specifically binds to oxalate, a key component of kidney calculi, was identified. Through isothermal titration calorimetry, high-performance liquid chromatography and atomic force microscopy, arbutin was determined to interact with calcium and oxalate in both free and bound states, disrupting crystal lattice structure, growth and crystallization. When used to treat patient urine samples, arbutin significantly abrogated calculus formation in vivo and outperformed potassium citrate in low pH urine conditions, owing to its oxalate-centric mode of action. The discovery of this novel antilithogenic compound via D. melanogaster, independent of a mammalian model, brings greater recognition to this platform, for which metabolic features are primary outcomes, underscoring the power of D. melanogaster as a high-throughput drug screening platform in similar disorders. This is the first description of the use of D. melanogaster as the model system for a high-throughput chemical library screen. This article has an associated First Person interview with the first authors of the paper.

As in Real Estate, Location Is What Matters: A Case Report of Transplant Ureteral Obstruction Due to an Inguinal Hernia.

BACKGROUND: Kidney allograft dysfunction is common and often reversible but can lead to allograft loss if not promptly evaluated. Transplant ureteral obstruction in an inguinal hernia is a rare cause of allograft dysfunction, but early recognition may prevent allograft loss. CASE PRESENTATION: We present a case of a man with acute kidney allograft dysfunction who received a deceased donor kidney transplant 6 years earlier for end-stage kidney disease secondary to polycystic kidney disease. Abdominal ultrasounds revealed hydronephrosis without full visualization of the transplant ureter. Abdominal computed tomography revealed moderate hydronephrosis of the transplant kidney due to obstructed herniation of the transplant ureter in a right inguinal hernia. A stent was inserted into the transplant ureter to prevent further allograft dysfunction and facilitate hernia repair. CONCLUSIONS: Transplant ureteral obstruction is a rare cause of acute kidney allograft dysfunction, and its detection can be challenging. The recognition of transplant ureteral obstruction is vital to timely management for preventing allograft loss.

CONTEXTE: Les dysfonctionnements des allogreffes rénales sont fréquents, quoique souvent réversibles. Ils peuvent toutefois mener à la perte du greffon s'ils ne sont pas décelés rapidement. En présence d'une hernie inguinale, la détection précoce de l'obstruction de l'uretère du greffon, une cause rare de ces troubles fonctionnels, peut prévenir la perte du rein greffé. PRÉSENTATION DU CAS: Nous exposons le cas d'un homme ayant reçu, six ans plus tôt, une greffe de rein provenant d'un donneur décédé pour soigner une insuffisance rénale terminale résultant d'une polykystose rénale. Le patient présentait un cas aigu de dysfonctionnement du greffon. L'échographie abdominale a révélé la présence d'une hydronéphrose sans que l'uretère soit complètement visible. La tomodensitométrie abdominale a quant à elle révélé une hydronéphrose modérée dans le rein transplanté due à l'obstruction de l'uretère dans l'hernie inguinale du côté droit. Une endoprothèse a été insérée dans l'uretère du greffon pour empêcher l'aggravation des troubles fonctionnels et pour faciliter la réparation herniaire. CONCLUSION: L'obstruction de l'uretère est une cause rare du dysfonctionnement aigu d'un rein transplanté, et sa détection peut représenter un véritable défi. Le diagnostic de ce type d'occlusion est crucial pour intervenir rapidement et ainsi prévenir la perte du greffon.

Neonicotinoid-induced pathogen susceptibility is mitigated by Lactobacillus plantarum immune stimulation in a Drosophila melanogaster model.

Pesticides are used extensively in food production to maximize crop yields. However, neonicotinoid insecticides exert unintentional toxicity to honey bees (Apis mellifera) that may partially be associated with massive population declines referred to as colony collapse disorder. We hypothesized that imidacloprid (common neonicotinoid; IMI) exposure would make Drosophila melanogaster (an insect model for the honey bee) more susceptible to bacterial pathogens, heat stress, and intestinal dysbiosis. Our results suggested that the immune deficiency (Imd) pathway is necessary for D. melanogaster survival in response to IMI toxicity. IMI exposure induced alterations in the host-microbiota as noted by increased indigenous Acetobacter and Lactobacillus spp. Furthermore, sub-lethal exposure to IMI resulted in decreased D. melanogaster survival when simultaneously exposed to bacterial infection and heat stress (37 °C). This coincided with exacerbated increases in TotA and Dpt (Imd downstream pro-survival and antimicrobial genes, respectively) expression compared to controls. Supplementation of IMI-exposed D. melanogaster with Lactobacillus plantarum ATCC 14917 mitigated survival deficits following Serratia marcescens (bacterial pathogen) septic infection. These findings support the insidious toxicity of neonicotinoid pesticides and potential for probiotic lactobacilli to reduce IMI-induced susceptibility to infection.

Probiotic Lactobacillus rhamnosus Reduces Organophosphate Pesticide Absorption and Toxicity to Drosophila melanogaster.

Organophosphate pesticides used in agriculture can pose health risks to humans and wildlife. We hypothesized that dietary supplementation with Lactobacillus, a genus of commensal bacteria, would reduce absorption and toxicity of consumed organophosphate pesticides (parathion and chlorpyrifos [CP]). Several Lactobacillus species were screened for toleration of 100 ppm of CP or parathion in MRS broth based on 24-h growth curves. Certain Lactobacillus strains were unable to reach stationary-phase culture maxima and displayed an abnormal culture morphology in response to pesticide. Further characterization of commonly used, pesticide-tolerant and pesticide-susceptible, probiotic Lactobacillus rhamnosus strain GG (LGG) and L. rhamnosus strain GR-1 (LGR-1), respectively, revealed that both strains could significantly sequester organophosphate pesticides from solution after 24-h coincubations. This effect was independent of metabolic activity, as L. rhamnosus GG did not hydrolyze CP and no difference in organophosphate sequestration was observed between live and heat-killed strains. Furthermore, LGR-1 and LGG reduced the absorption of 100 µM parathion or CP in a Caco-2 Transwell model of the small intestine epithelium. To determine the effect of sequestration on acute toxicity, newly eclosed Drosophila melanogaster flies were exposed to food containing 10 µM CP with or without supplementation with live LGG. Supplementation with LGG simultaneously, but not with administration of CP 3 days prior (prophylactically), mitigated CP-induced mortality. In summary, the results suggest that L. rhamnosus may be useful for reducing toxic organophosphate pesticide exposure via passive binding. These findings could be transferable to clinical and livestock applications due to affordability and practical ability to supplement products with food-grade bacteria. IMPORTANCE: The consequences of environmental pesticide pollution due to widespread usage in agriculture and soil leaching are becoming a major societal concern. Although the long-term effects of low-dose pesticide exposure for humans and wildlife remain largely unknown, logic suggests that these chemicals are not aligned with ecosystem health. This observation is most strongly supported by the agricultural losses associated with honeybee population declines, known as colony collapse disorder, in which pesticide usage is a likely trigger. Lactobacilli are bacteria used as beneficial microorganisms in fermented foods and have shown potentials to sequester and degrade environmental toxins. This study demonstrated that commonly used probiotic strains of lactobacilli could sequester, but not metabolize, organophosphate pesticides (parathion and chlorpyrifos). This Lactobacillus-mediated sequestration was associated with decreased intestinal absorption and insect toxicity in appropriate models. These findings hold promise for supplementing human, livestock, or apiary foods with probiotic microorganisms to reduce organophosphate pesticide exposure.

Natural History of Residual Fragments After Percutaneous Nephrolithotomy: Evaluation of Factors Related to Clinical Events and Intervention.

OBJECTIVE: To determine the natural history of residual fragments (RF) after percutaneous nephrolithotomy in long-term patient follow-up and to identify possible predictive factors for future intervention. MATERIALS AND METHODS: We assessed all patients from 2006 to 2013 with postoperative computed tomography scan revealing RF, who did not undergo second-look nephroscopy or immediate ancillary procedures, and with at least 12 months of clinical follow-up. We evaluated factors associated with clinical, radiological, and surgical outcomes. Kaplan-Meier curves were used to calculate the proportion of asymptomatic and treatment-free patients during follow-up. RESULTS: From 781 percutaneous nephrolithotomies performed, 202 patients underwent postoperative computed tomography scan and 44 patients with residual stones were included in the analysis. Mean follow-up was 57.9 months. A total of 24 patients (54.5%) developed at least 1 clinical outcome, and 32 (72.7%) patients had a surgical intervention. Only 4 patients had radiological evidence of stone passage. Multivariate analysis found that RF >4 mm and struvite or apatite stones were significant predictors for surgical intervention. The 5-year estimated probability to remain intervention free was 29%. CONCLUSION: Despite the size of the RF, the vast majority of patients required an intervention during long-term follow-up. We identified that RFs of diameter >4 mm associate with the need for a surgical therapy, but the rate of clinical events was not affected by the size or location of the stones. Struvite or apatite composition stones had an increased risk of intervention during follow-up. Spontaneous passage was an uncommon event in this cohort.

Novel Methods of Determining Urinary Calculi Composition: Petrographic Thin Sectioning of Calculi and Nanoscale Flow Cytometry Urinalysis.

Accurate determination of urinary stone composition has significant bearing on understanding pathophysiology, choosing treatment modalities and preventing recurrence. A need exists for improved methods to determine stone composition. Urine of 31 patients with known renal calculi was examined with nanoscale flow cytometry and the calculi collected during surgery subsequently underwent petrographic thin sectioning with polarized and fluorescent microscopy. Fluorescently labeled bisphosphonate probes (Alendronate-fluorescein/Alendronate-Cy5) were developed for nanoscale flow cytometry to enumerate nanocrystals that bound the fluorescent probes. Petrographic sections of stones were also imaged by fluorescent and polarized light microscopy with composition analysis correlated to alendronate +ve nanocrystal counts in corresponding urine samples. Urine samples from patients with Ca(2+) and Mg(2+) based calculi exhibited the highest alendronate +ve nanocrystal counts, ranging from 100-1000 nm in diameter. This novel urine based assay was in agreement with composition determined by petrographic thin sections with Alendronate probes. In some cases, high alendronate +ve nanocrystal counts indicated a Ca(2+) or Mg(2+) composition, as confirmed by petrographic analysis, overturning initial spectrophotometric diagnosis of stone composition. The combination of nanoscale flow cytometry and petrographic thin sections offer an alternative means for determining stone composition. Nanoscale flow cytometry of alendronate +ve nanocrystals alone may provide a high-throughput means of evaluating stone burden.