Development and Initial Evaluation of a Cost-Effective Force Sensor for Ureteroscopic Application.

Purpose: Retrograde intrarenal surgery is the gold-standard treatment for most kidney stones. During ureteroscopy, ureteral access sheath insertion at forces greater than 8.0 Newtons (N) risks high-grade ureteral injury. To monitor force, our institution utilizes a unique, Bluetooth-equipped device (i.e., the University of California-Irvine Force Sensor). Given the unique nature of the force sensor, we sought to develop an inexpensive and accessible force sensor based on Boyle's law and the specific amount of force required to compress an occluded 1.0 mL syringe. Materials and Methods: We evaluated three brands of 1.0 mL syringes. After setting the plunger at 1.0 mL, the syringe was occluded, and the syringe plunger was compressed. The syringe volume was recorded when the applied force on the plunger reached 4.0 N, 6.0 N, and 8.0 N. Multiple trials were performed to assess reliability and reproducibility. A method for applying this clinically was also developed. Results: The precise force thresholds identified for a 1.0 mL Luer-Lok™ Syringe (Becton Dickinson, Franklin Lakes, NJ) were 0.30 mL for 4.00 N, 0.20 mL for 6.00 N, and 0.15 mL for 8.00 N. The 1.0 mL Tuberculin Syringe and 1.0 mL Luer Slip Syringe were less precise, but compression from 1.0 to 0.40 mL, 0.25 mL, and 0.20 mL corresponded to force sensor readings that did not exceed 4.00 N, 6.00 N, and 8.00 N, respectively. Conclusions: Based on volume changes, 4.00 N, 6.00 N, and 8.00 N of force can be reliably and reproducibly achieved using an occluded 1.0 mL syringe.

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.

Surgical Force: Initial Study and Clinical Implications in the Assessment of Ureteral Access Sheath Induced Injury.

Purpose: Ureteral access sheaths (UAS) pose the risk of severe ureteral injury. Our prior studies revealed forces ≤6 Newtons (N) prevent ureteral injury. Accordingly, we sought to define the force urologists and residents in training typically use when placing a UAS. Materials and Methods: Among urologists and urology residents attending two annual urological conferences in 2022, 121 individuals were recruited for the study. Participants inserted 12F, 14F, and 16F UAS into a male genitourinary model containing a concealed force sensor; they also provided demographic information. Analysis was completed using t-tests and Chi-square tests to identify group differences when passing a 16F sheath UAS. Participant traits associated with surpassing or remaining below a minimal force threshold were also explored through polychotomous logistic regression. Results: Participant force distributions were as follows: ≤4N (29%), >6N (45%), and >8N (32%). More years of practice were significantly associated with exerting >6N relative to forces between 4N and 6N; results for >8N relative to 4N and 8N were similar. Compared to high-volume ureteroscopists (those performing >20 ureteroscopies/month), physicians performing ≤20 ureteroscopies/month were significantly less likely to exert forces ≤4N (p = 0.017 and p = 0.041). Of those surpassing 6N and 8N, 15% and 18%, respectively, were high-volume ureteroscopists. Conclusions: Despite years of practice or volume of monthly ureteroscopic cases performed, most urologists failed to pass 16F access sheaths within the ideal range of 4N to 6N (74% of participants) or within a predefined safe range of 4N to 8N (61% of participants).

Alkaline Water: Help or Hype for Uric Acid and Cystine Urolithiasis?

PURPOSE: The consumption of alkaline water, water with an average pH of 8 to 10, has been steadily increasing globally as proponents claim it to be a healthier alternative to regular water. Urinary alkalinization therapy is frequently prescribed in patients with uric acid and cystine urolithiasis, and as such we analyzed commercially available alkaline waters to assess their potential to increase urinary pH. MATERIALS AND METHODS: Five commercially available alkaline water brands (Essentia, Smart Water Alkaline, Great Value Hydrate Alkaline Water, Body Armor SportWater, and Perfect Hydration) underwent anion chromatography and direct chemical measurements to determine the mineral contents of each product. The alkaline content of each bottle of water was then compared to that of potassium citrate (the gold standard for urinary alkalinization) as well as to other beverages and supplements used to augment urinary citrate and/or the urine pH. RESULTS: The pH levels of the bottled alkaline water ranged from 9.69 to 10.15. Electrolyte content was minimal, and the physiologic alkali content was below 1 mEq/L for all brands of alkaline water. The alkali content of alkaline water is minimal when compared to common stone treatment alternatives such as potassium citrate. In addition, several organic beverages, synthetic beverages, and other supplements contain more alkali content than alkaline water, and can achieve the AUA and European Association of Urology alkali recommendation of 30 to 60 mEq per day with ≤ 3 servings/d. CONCLUSIONS: Commercially available alkaline water has negligible alkali content and thus provides no added benefit over tap water for patients with uric acid and cystine urolithiasis.

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.

Efficient and Accurate Computed Tomography-Based Stone Volume Determination: Development of an Automated Artificial Intelligence Algorithm.

PURPOSE: Given the shortcomings of current stone burden characterization (maximum diameter or ellipsoid formulas), we sought to investigate the diagnostic accuracy and precision of a University of California, Irvine-developed artificial intelligence (AI) algorithm for determining stone volume determination. MATERIALS AND METHODS: A total of 322 noncontrast CT scans were retrospectively obtained from patients with a diagnosis of urolithiasis. The largest stone in each noncontrast CT scan was designated the "index stone." The 3D volume of the index stone using 3D Slicer technology was determined by a validated reviewer; this was considered the "ground truth" volume. The AI-calculated index stone volume was subsequently compared with ground truth volume as well with the scalene, prolate, and oblate ellipsoid formulas estimated volumes. RESULTS: There was a nearly perfect correlation between the AI-determined volume and the ground truth (R=0.98). While the AI algorithm was efficient for determining the stone volume for all sizes, its accuracy improved with larger stone size. Moreover, the AI stone volume produced an excellent 3D pixel overlap with the ground truth (Dice score=0.90). In comparison, the ellipsoid formula-based volumes performed less well (R range: 0.79-0.82) than the AI algorithm; for the ellipsoid formulas, the accuracy decreased as the stone size increased (mean overestimation: 27%-89%). Lastly, for all stone sizes, the maximum linear stone measurement had the poorest correlation with the ground truth (R range: 0.41-0.82). CONCLUSIONS: The University of California, Irvine AI algorithm is an accurate, precise, and time-efficient tool for determining stone volume. Expanding the clinical availability of this program could enable urologists to establish better guidelines for both the metabolic and surgical management of their urolithiasis patients.

Ex vivo pleural effusion cultures to study chimeric antigen receptor T cell cytotoxicity in an immunocompetent environment.

Current in vitro and in vivo assays used to study immunotherapeutic interventions lack human immune components that mimic the tumor microenvironment to investigate drug potency and limitations of efficacy. Herein, we describe an ex vivo pleural effusion culture (ePEC) assay, using malignant pleural-effusion-derived soluble and cellular factors that differentially affected the cytotoxicity of chimeric antigen receptor (CAR) T cells. Following identification of CAR T cell-suppressive factors, blocking of individual factors reveals their contribution to compromising T cell efficacy. ePEC is a human component assay that can be utilized for developing next-generation cell and antibody therapies that counteract immunosuppression.

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.

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.

Driving CARs on the uneven road of antigen heterogeneity in solid tumors.

Uniform and strong expression of CD19, a cell surface antigen, on cells of B-cell lineage is unique to hematologic malignancies. Tumor-associated antigen (TAA) targets in solid tumors exhibit heterogeneity with regards to intensity and distribution, posing a challenge for chimeric antigen receptor (CAR) T-cell therapy. Novel CAR designs, such as dual TAA-targeted CARs, tandem CARs, and switchable CARs, in conjunction with inhibitory CARs, are being investigated as means to overcome antigen heterogeneity. In addition to heterogeneity in cancer-cell antigen expression, the key determinants for antitumor responses are CAR expression levels and affinity in T cells. Herein, we review CAR T-cell therapy clinical trials for patients with lung or pancreatic cancers, and provide detailed translational strategies to overcome antigen heterogeneity.

Novel immunotherapy clinical trials in malignant pleural mesothelioma.

In this article, we review ongoing novel clinical trials currently investigating immunotherapeutic approaches for patients with malignant pleural mesothelioma (MPM). There is a dearth of effective therapeutic options for patients diagnosed with MPM and metastatic cancers of the pleura; these diseases have an estimated annual incidence of 150,000. Modulating the immune microenvironment to promote antitumor immune responses by systemically and regionally delivered therapeutic agents is an active area of investigation. We have conducted a review of the clinical trials database for clinical trials actively recruiting MPM patients. We focused on novel therapeutic agents administered either systemically or intrapleurally to modulate the tumor immune microenvironment. Herein, we have summarized the published results of early phase clinical trials. A total of 43 clinical trials met our inclusion criteria. These trials are investigating immunologic agents (n=20) and antibody directed therapies (n=23). The regional intrapleural delivery technique (6 trials) is used to administer chemotherapy agents (3 of 6 trials) and immunotherapy agents (3 of 6 trials), including chimeric antigen receptor T cells (1 of 6 trials). Current clinical trials modulating the MPM immune microenvironment and the combination of these novel agents with standard of care therapy provide a promising area of investigation for MPM therapy.

CAR T-cell therapy for pancreatic cancer.

Chimeric antigen receptor (CAR) T-cell therapy utilizes genetic engineering to redirect a patient's own T cells to target cancer cells. The remarkable results in hematological malignancies prompted investigating this approach in solid tumors such as pancreatic cancer. The complex tumor microenvironment, stromal hindrance in limiting immune response, and expression of checkpoint blockade on T cells pose hurdles. Herein, we summarize the opportunities, challenges, and state of knowledge in targeting pancreatic cancer with CAR T-cell therapy.