Targeting prostate cancer with Clostridium perfringens enterotoxin functionalized nanoparticles co-encapsulating imaging cargo enhances magnetic resonance imaging specificity.

Magnetic resonance is a key imaging tool for the detection of prostate cancer; however, better tools focusing on cancer specificity are required to distinguish benign from cancerous regions. We found higher expression of claudin-3 (CLDN-3) and -4 (CLDN-4) in higher grade than lower-grade human prostate cancer biopsies (n = 174), leading to the design of functionalized nanoparticles (NPs) with a non-toxic truncated version of the natural ligand Clostridium perfringens enterotoxin (C-CPE) that has a strong binding affinity to Cldn-3 and Cldn-4 receptors. We developed a first-of-its-type, C-CPE-NP-based MRI detection tool in a prostate tumor-bearing mouse model. NPs with an average diameter of 152.9 ±â€¯15.7 nm (RS1) had a 2-fold enhancement of tumor specificity compared to larger (421.2 ±â€¯33.8 nm) NPs (RS4). There was a 1.8-fold (P < 0.01) and 1.6-fold (P < 0.01) upregulation of the tumor-to-liver signal intensities of C-RS1 and C-RS4 (functionalized NPs) compared to controls, respectively. Also, tumor specificity was 3.1-fold higher (P < 0.001) when comparing C-RS1 to C-RS4. This detection tool improved tumor localization of contrast-enhanced MRI, supporting potential clinical applicability.

Distinguishing Benign Renal Tumors with an Oncocytic Gene Expression (ONEX) Classifier.

Renal oncocytoma (RO) accounts for 5% of renal cancers and generally behaves as a benign tumor with favorable long-term prognosis. It is difficult to confidently distinguish between benign RO and other renal malignancies, particularly chromophobe renal cell carcinoma (chRCC). Therefore, RO is often managed aggressively with surgery. We sought to identify molecular biomarkers to distinguish RO from chRCC and other malignant renal cancer mimics. In a 44-patient discovery cohort, we identified a significant differential abundance of nine genes in RO relative to chRCC. These genes were used to train a classifier to distinguish RO from chRCC in an independent 57-patient cohort. The trained classifier was then validated in five independent cohorts comprising 89 total patients. This nine-gene classifier trained on the basis of differential gene expression showed 93% sensitivity and 98% specificity for distinguishing RO from chRCC across the pooled validation cohorts, with a c-statistic of 0.978. This tool may be a useful adjunct to other diagnostic modalities to decrease the diagnostic and management uncertainty associated with small renal masses and to enable clinicians to recommend more confidently less aggressive management for some tumors. PATIENT SUMMARY: Renal oncocytoma is generally a benign form of kidney cancer that does not necessarily require surgical removal. However, it is difficult to distinguish renal oncocytoma from other more aggressive forms of kidney cancer, so it is treated most commonly with surgery. We built a classification tool based on the RNA levels of nine genes that may help avoid these surgeries by reliably distinguishing renal oncocytoma from other forms of kidney cancer.

A non-enzymatic method for dissection of mouse bladder urothelial tissue.

Urothelial cells contribute to bladder functions, including urine storage, urine emptying, and innate immune response. Functional studies of urothelial cells usually use either freshly isolated cells or cultured cells. Most methods of isolating urothelial cells require enzymes; however, these techniques remove proteins that connect the cells and disrupt the orientation of the cells within the multilayered urothelium. In addition, PCR or immunoblot results obtained from homogenates of bladder mucosa or whole bladder do not represent pure urothelial cells. We describe a dissection process that does not require enzymes and is able to obtain pure urothelial tissues from mice and humans. This method can isolate single urothelial cells for electrophysiology in situ and can also isolate pure urothelial tissue for PCR, microarray, and immunoblot procedures. The time required to obtain urothelial tissue from one mouse bladder is 15-20 min. This method is simple and time efficient as compared with alternative methods and therefore facilitates our understanding of urothelial biology.

The Yale Center for Biomedical Innovation and Technology (CBIT): One Model to Accelerate Impact From Academic Health Care Innovation.

The process of translating academic biomedical advances into clinical care improvements is difficult, risky, expensive, and poorly understood. Notably, many clinicians who identify health care problems do not have the time or expertise to solve the problems, and many academic researchers are unaware of important gaps in clinical care to which their expertise may apply.Recognizing an opportunity to connect people who can identify health care problems with those who can solve them, the Yale Center for Biomedical Innovation and Technology (CBIT) was established in 2014 to educate and enhance the impact of health care innovators. The authors review other health care innovation centers and describe best practices borrowed by Yale CBIT, which tailored its activities and approach to its unique ecosystem.In four years, Yale CBIT has affected over 3,000 people and established a health care innovation cycle as an efficient strategy to guide translational research. Yale CBIT has created or supported graduate and undergraduate courses, clinical immersion programs for industry partners, and large health care hackathon events. Over 200 projects have been submitted to CBIT for mentorship, and some of those projects have been commercialized and raised millions of dollars of follow-on funding.The authors present Yale CBIT as one model of accelerating the impact of academic medicine on clinical practice and outcomes. The project advising strategy is intended to be a template to maximize the efficiency of biomedical innovation and ultimately improve the outcomes and experiences of future patients.

Prostate zonal anatomy correlates with the detection of prostate cancer on multiparametric magnetic resonance imaging/ultrasound fusion-targeted biopsy in patients with a solitary PI-RADS v2-scored lesion.

PURPOSE: To evaluate the positive predictive value (PPV) of the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) assessment method in patients with a single suspicious finding on prostate multiparametric magnetic resonance imaging (mpMRI). PATIENTS AND METHODS: A total of 176 patients underwent MRI/ultrasound fusion-targeted prostate biopsy after the detection of a single suspicious finding on mpMRI. The PPV for cancer detection was determined based on PI-RADS v2 assessment score and location. RESULTS: Fusion biopsy detected prostate cancer in 60.2% of patients. Of these patients, 69.8% had Gleason score (GS) ≥7 prostate cancer. Targeted biopsy detected 90.5% of all GS≥7 prostate cancer. The PPV for GS≥7 detection of PI-RADS v2 category 5 (P5) and category 4 (P4) lesions was 70.2% and 37.7%, respectively. This increased to 88% and 38.5% for P5 and P4 lesions in the peripheral zone (PZ), respectively. Targeted biopsy did not miss GS≥7 disease compared with systematic biopsy in P5 lesions in the PZ and transition zone. CONCLUSION: The PPV of PI-RADS v2 for prostate cancer in patients with a single lesion on mpMRI is dependent on PI-RADS assessment category and location. The highest PPV was for a P5 lesion in the PZ.

Negative Multiparametric Magnetic Resonance Imaging of the Prostate Predicts Absence of Clinically Significant Prostate Cancer on 12-Core Template Prostate Biopsy.

OBJECTIVE: To determine the negative predictive value of multiparametric magnetic resonance imaging (mpMRI), we evaluated the frequency of prostate cancer detection by 12-core template mapping biopsy in men whose mpMRI showed no suspicious regions. METHODS: Six hundred seventy patients underwent mpMRI followed by transrectal ultrasound (TRUS)-guided systematic prostate biopsy from December 2012 to June 2016. Of this cohort, 100 patients had a negative mpMRI. mpMRI imaging sequences included T2-weighted and diffusion-weighted imaging, and dynamic contrast enhancement sequences. RESULTS: The mean age, prostate-specific antigen, and prostate volume of the 100 men included were 64.3 years, 7.2 ng/mL, and 71 mL, respectively. Overall cancer detection was 27% (27 of 100). Prostate cancer was detected in 26.3% (10 of 38) of patients who were biopsy-naïve, 12.1% (4 of 33) of patients who had a prior negative biopsy, and in 44.8% (13 of 29) of patients previously on active surveillance; Gleason grade ≥7 was detected in 3% of patients overall (3 of 100). The negative predictive value of a negative mpMRI was 73% for all prostate cancer and 97% for Gleason ≥7 prostate cancer. CONCLUSION: There is an approximately 3% chance of detecting clinically significant prostate cancer with systematic TRUS-guided biopsy in patients with no suspicious findings on mpMRI. This information should help guide recommendations to patients about undergoing systematic TRUS-guided biopsy when mpMRI is negative.

Evolution of laparoscopic donor nephrectomy technique and outcomes: a single-center experience with more than 1300 cases.

OBJECTIVE: To describe and illustrate the evolution of surgical technique, emphasizing technical modifications of laparoscopic donor nephrectomy (LDN) and the impact on complication outcome. METHODS: This is a retrospective observational study of prospectively collected data on all consecutive purely LDN surgeries performed at a tertiary academic medical center (n = 1325), performed between March 2000 and October 2013. RESULTS: Over time, LDN was performed on older patients, changing from a mean of 35.7 years in 2000 to 41.2 years in 2013 (P <.001). Additionally, mean blood loss decreased from 75 mL in 2000 to 21.6 mL in 2013 (P <.001). However, body mass index, operative time, and length of stay remained similar. Overall, there were 105 (7.9%) complications: Clavien grade 1 (n = 81, 6.1%) and grade 2 or higher (n = 23, 1.8%). Procedure duration, blood loss, surgeon, year of procedure, laterality, body mass index, age, and gender did not significantly predict complications. There was no significant difference for Clavien complication rates between the early learning period (first 150 cases) and the rest of the series. CONCLUSION: With continual refinement with LDN techniques based on intraoperative observations and technological advances, complication rates remain consistently low, despite increasing donor age.

Association of type of renal surgery and access to robotic technology for kidney cancer: results from a population-based cohort.

OBJECTIVE: To evaluate the relationship between partial nephrectomy (PN) and hospital availability of robot-assisted surgery from a population-based cohort in the USA. METHODS: After merging the Nationwide Inpatient Sample (NIS) and the American Hospital Association survey from 2006 to 2008, we identified 21 179 patients who underwent either PN or radical nephrectomy (RN) for renal cell carcinoma (RCC). The primary outcome assessed was the type of nephrectomy performed. Multivariable logistic regression identified the patient and hospital characteristics associated with receipt of PN. RESULTS: We identified 4832 (22.8%) and 16 347 (77.2%) patients who were treated for RCC with PN and RN, respectively. On multivariable analysis, patients were more likely to receive PN at academic centres (odds ratio [OR] 2.77; P < 0.001), urban centres (OR 3.66; P < 0.001) and American College of Surgeons (ACOS)-designated cancer centres (OR: 1.10; P < 0.05) compared with non-academic, rural and non-ACOS-designated cancer centre hospitals, respectively. Robot-assisted surgery availability at a hospital was also associated with a higher adjusted odds of PN compared with centres without that availability (OR 1.28; P < 0.001). CONCLUSIONS: Although academic and urban locations are established factors that affect the receipt of PN for RCC, the availability of robot-assisted surgery at a hospital was also independently associated with higher use of PN. Our results are informative in identifying other key hospital characteristics which may facilitate greater adoption of PN.

Determinants of laparoscopic donor nephrectomy outcomes.

BACKGROUND: Pure laparoscopic donor nephrectomy (LDN) is a unique intervention because it carries known risks and complications, yet carries no direct benefit to the donor. Therefore, it is critical to continually examine and improve quality of care. OBJECTIVE: To identify factors affecting LDN outcomes and complications. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of prospectively collected data for 1204 consecutive LDNs performed from March 2000 through August 2012. INTERVENTION: LDN performed at an academic training center. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Using multivariable regression, we assessed the effect of age, sex, body mass index (BMI), laterality, and vascular variation on operative time, estimated blood loss (EBL), complications, and length of stay. RESULTS AND LIMITATIONS: The following variables were associated with longer operative time (data given as parameter estimate plus or minus the standard error): female sex (9.09 ± 2.43; p<0.001), higher BMI (1.03 ± 0.32; p=0.001), two (7.87 ± 2.70; p=0.004) and three or more (22.45 ± 7.13; p=0.002) versus one renal artery, and early renal arterial branching (5.67 ± 2.82; p=0.045), while early renal arterial branching (7.81 ± 3.85; p=0.043) was associated with higher EBL. Overall, 8.2% of LDNs experienced complications, and by modified Clavien classification, 74 (5.9%) were grade 1, 13 (1.1%) were grade 2a, 10 (0.8%) were grade 2b, and 2 (0.2%) were grade 2c. There were no grade 3 or 4 complications. Three or more renal arteries (odds ratio [OR]: 2.74; 95% CI, 1.05-7.16; p=0.04) and late renal vein confluence (OR: 2.42; 95% CI, 1.50-3.91; p=0.0003) were associated with more complications. Finally, we did not find an association of the independent variables with length of stay. A limitation is that warm ischemia time was not assessed. CONCLUSIONS: In our series, renal vascular variation prolonged operative time and was associated with more complications. While complicated donor anatomy is not a contraindication of LDN, surgical decision-making should take into consideration these results.

A transurethral catheter-based ultrasound system for multi-modal fusion.

Current methods of prostate cancer diagnosis and therapy rely on accurate imaging of the prostate using real-time ultrasound. Transurethral ultrasound (TUUS) may improve upon the current gold standard through improved 3D visualization and co-registration (fusion) with CT and MRI. A prototype transurethral ultrasound (TUUS) catheter-based transducer array and system was developed, featuring 32 elements with a diameter of 18F (6mm). A robust, multi-channel ultrasound transceiver was also developed to enable TUUS imaging using pulse-echo and frequency-based signal processing methods. The feasibility of a TUUS imaging system suitable for multi-modal image fusion and novel ultrasound signaling techniques was demonstrated.

Standardized linear port configuration to improve operative ergonomics in laparoscopic renal and adrenal surgery: experience with 1264 cases.

BACKGROUND AND PURPOSE: Traditional laparoscopic port placement for upper urinary tract surgery involves camera access via the umbilicus with working ports placed on either side of the camera at various locations. This diamond configuration requires the camera operator to cross hands with the surgeon, resulting in poor ergonomics. A standardized linear port configuration has been used for nearly all transperitoneal urologic surgery at our institution. The purpose of this article is to describe our experience with this simplified approach and its advantages. PATIENTS AND METHODS: A retrospective review was conducted of all laparoscopic cases by a single surgeon from 2000 to June 2009. The linear port configuration includes three ports placed along the ipsilateral pararectal line with the most superior port one fingerbreadth below the costal margin and the inferior port at the level of the umbilicus. A 5-mm camera is used through the most superior port. A low transverse extraction site is typically used, if necessary. RESULTS: There were 1264 laparoscopic cases performed using the linear port configuration. Of these, there were 1038 donor/radical/simple and 60 partial nephrectomies, 35 nephroureterectomies, 49 adrenalectomies, 50 pyeloplasties, 20 renal cryoablations, and 12 miscellaneous renal procedures. Of these, 98.2% were performed successfully via this port configuration. Three cases needed an additional port. The intraoperative complication rate was 0.9%, and mean estimated blood loss was 60 mL. There were 20 (1.6%) open conversions: 16 were elective and 4 secondary to complications. CONCLUSION: Simplifying port placement via a linear configuration for both right and left renal and adrenal surgery is feasible, easy to learn, simplifies strategic planning preoperatively, and provides excellent exposure. Using camera access through the superior port allows for direct visualization and minimizes interaction between the camera holder and surgeon's working envelope.

Laparoendoscopic single-site porcine nephrectomy using a novel valveless trocar system.

BACKGROUND AND PURPOSE: The AirSeal™ access system is a novel laparoscopic trocar that uses airflow to create insufflation pressure without the need for a physical seal or valve. By eliminating all valve elements within the lumen of the canula, the port provides a platform that accommodates multiple instruments of any diameter, shape, or combination and is ideally suited for laparoendoscopic single-site surgery (LESS). We present our initial experience with valveless trocars in traditional urologic laparoscopic cases and a porcine LESS nephrectomy series. MATERIALS AND METHODS: Nine transperitoneal LESS nephrectomies were performed in a live porcine model using the 27-mm oval valveless trocar. All working instruments were placed through the single port, and the specimen was extracted through the 4-cm port site. RESULTS: All cases were completed without technical or operative complications. The porcine single-port nephrectomy (n=9) was successfully performed in a mean operative time of 24 minutes through the single 27-mm oval trocar. This accommodated a 5-mm laparoscope, multiple 5-mm instruments, the Endo GIA stapler, and the 15-mm Endocatch bag without loss of insufflation pressure. Condensation and smudging of the laparoscope were minimized, improving visualization and efficiency. The system allowed for use of suction without significant loss of insufflation pressure. CONCLUSION: The initial experience with the AirSeal valveless trocar system in LESS is encouraging. This technology may offer significant benefits over traditional laparoscopic trocars and single -port platforms and appears particularly suited to facilitate LESS.

Percutaneous cystolithotomy for calculi in reconstructed bladders: initial UCLA experience.

PURPOSE: Following bladder augmentation, patients are at significant risk for bladder calculi. We present our experience with a minimally invasive treatment approach using endoscopically assisted percutaneous cystolithotomy. MATERIALS AND METHODS: A retrospective chart review identified 74 patients who underwent percutaneous cystolithotomy following bladder augmentation between 2002 and 2009. Cystogram was performed to determine the ideal location for percutaneous bladder access and a guidewire was inserted in the bladder through a bile needle. A balloon dilator was used to place a 30Fr sheath. Rigid cystoscopy with a 26Fr nephroscope allowed stone treatment by basketing and ultrasonic lithotripsy. A suprapubic 22Fr catheter was then placed. Patients were seen on postoperative day 14 and abdominal ultrasound was performed. If no significant residual calculi were visualized, the suprapubic tube was removed. RESULTS: Mean +/- SD patient age at operation was 20 +/- 10.7 months (range 4 to 40). Mean +/- SD time between bladder augmentation and percutaneous cystolithotomy was 4.8 +/- 2.05 years. Of the patients 38 (51%) were male and 36 (49%) were female. Mean +/- SD number of stones per patient was 4.6 +/- 7.8 (range 1 to 60). Ultrasonic lithotripsy was performed in 49 cases (66%). In 25 cases (34%) only stone basketing was performed. A total of 70 patients (95%) were stone-free on abdominal plain film at 14 days. Of the procedures 24 (32%) were performed on an outpatient basis and 50 were performed on an inpatient basis with a mean +/- SD hospital stay of 1.3 +/- 2.7 days (range 1 to 21). There were 9 minor complications noted (12%). CONCLUSIONS: Endoscopic percutaneous cystolithotomy offers a safe and effective treatment option for bladder calculi in reconstructed bladders and is the preferred method at our institution.

Comparison of accuracy of 14-, 18- and 20-G needles in ex-vivo renal mass biopsy: a prospective, blinded study.

OBJECTIVE: To prospectively determine the accuracy of 14-, 18- and 20-G core needle biopsies to render the appropriate histological diagnosis of solid, enhancing renal masses, using a controlled, ex-vivo biopsy technique. PATIENTS AND METHODS: From March 2007 to September 2007, 31 patients undergoing partial or radical nephrectomy were randomly selected for biopsy. After extirpative surgery, three ex-vivo biopsies were taken from each lesion with 14-, 18- and 20-G biopsy needles. One experienced genitourinary pathologist, unaware of patient identifiers and final pathology results, determined the biopsy histology and tumour grade, based on standard haematoxylin and eosin (H&E) techniques and immunohistochemistry. RESULTS: The final pathological evaluation classified 21 masses (68%) as clear cell renal cell carcinoma (RCC), three (10%) as papillary RCC, three (10%) as chromophobe RCC, three (10%) as oncocytoma and one (3%) as a benign lymphoid infiltrate. The biopsy histology correlated with the final pathology in 29/31 cases (94%) with the 14-G, 30/31 cases (97%) with the 18-G and 25/31 cases (81%) with the 20-G needles. In two cases chromophobe RCC was misdiagnosed with oncocytoma, and vice versa. CONCLUSION: In this study a minimum of an 18-G biopsy needle was the most accurate in determining the histological diagnosis. Clear cell and papillary RCCs were accurately diagnosed on biopsy using an 18-G, whereas oncocytoma and chromophobe RCC were difficult to differentiate using standard H&E techniques and immunohistochemistry.

Flexible ureteroscopy and laser lithotripsy for multiple unilateral intrarenal stones.

BACKGROUND: External shock wave lithotripsy (ESWL) and percutaneous nephrolithotomy (PNL) have been the standard of care for the treatment of intrarenal calculi. OBJECTIVE: We sought to determine the safety and efficacy of flexible ureteroscopy and holmium laser lithotripsy for the treatment of multiple intrarenal calculi and further stratify the efficacy by stone burden less than and greater than 20mm. DESIGN, SETTING, AND PARTICIPANTS: Patients with multiple unilateral renal calculi treated between 2000 and 2006 at a single tertiary academic center were retrospectively evaluated. INTERVENTION: All patients underwent retrograde flexible ureteroscopy and holmium laser lithotripsy. MEASUREMENTS: Stone-free status was determined by ureteroscopy 15 d after the last procedure and was defined as the absence of stones in the kidney or residual fragments <1mm. A renal ultrasound was performed 30 d after the last treatment to confirm the absence of stones and hydronephrosis. RESULTS AND LIMITATIONS: Fifty-one patients were identified for a total of 161 intrarenal calculi with a mean stone size per patient of 6.6+/-3mm (range: 2-15). The mean number of stones per patient was 3.1+/-1 (range: 2-6). The mean number of primary procedures was 1.4+/-0.6 (range: 1-3). The overall stone-free rates after one and two procedures were 64.7% and 92.2%, respectively. The stone-free rates for patients with a stone burden greater than and less than 20mm were 85.1% and 100%, respectively. The overall complication rate was 13.6%; 97.6% of cases were performed as outpatient procedures. There are some limitations to this study, however: This is a retrospective review from a single institution, and our results are based on a relatively small sample size. CONCLUSIONS: For select patients with multiple intrarenal calculi, flexible ureteroscopy with holmium laser lithotripsy may represent an alternative therapy to ESWL or PNL, with acceptable efficacy and low morbidity.

Laparoscopic nephron sparing surgery: a multi-institutional European survey of 592 cases.

Laparoscopic Nephron Sparing Surgery (LNSS) is a technically challenging procedure. Technical aspects and the outcome of LNSS are investigated. A total of 592 LNSS procedures were collected from 12 Centres, either in extraperitoneal or transperitoneal fashion. Mean tumor size was 2.2 cm. Eight centers reported on tumor position for a total of 407 cases with 338 exophytic tumors (83%) and 69 deep lesions (17%). Four centers, accounting for 185 cases, did not report on tumor position. All the centers performed their LNSS by clamping the hilum. The warm ischemia time was < 30 min in all the centers. The positive margin rate was 2% (12/592). Hemostatic agents and/or sealant or tissue glues were used in 86% of cases (511/592). Types of sealants used included: gelatine matrix (Floseal), fibrin gel (Tissucol), bovine serum albumin (BioGlue) and cianacrylate (Glubran). Two Centres never used sealants, one center used only sealants without suturing and 9 centers used a combination of sealants and bolstering-sutures. The intraoperative open conversion rate was 3.5% (21/592). Postoperative complications included bleeding in 15/592 (2.5%) and urine leak in 13/592 (2.1%). No tumor seeding was reported. LNSS has similar results of open partial nephrectomy. The use of hemostatic agents and/or sealants or tissue glues during LNSS is largely diffuse in European centers and may be an effective add on reducing bleeding and urine leakage when used in combination with bolstering-suturing.

Importance of surgical margins in the management of renal cell carcinoma.

Surgical resection remains the standard treatment for clinically localized renal cell carcinoma. Pathological features of the surgical specimen, including the margin status, play an important part in determining the patient's prognosis. Negative surgical margins have traditionally been sought to maximize the efficacy of treatment. Initial concerns that partial nephrectomy might have high local recurrence rates compared with radical nephrectomy have now been minimized as a result of technological advances and refinements in surgical technique. Current concerns in relation to partial nephrectomy include the width of parenchymal tissue that should be removed to avoid positive surgical margins, effects of positive margins on recurrence-free survival, and the use of frozen-section analysis to determine margin status. Size of the surgical margin in partial nephrectomy does not seem to affect the risk of local tumor recurrence, and not all positive surgical margins lead to recurrent disease. Intraoperative frozen-section analysis is not definitive and its value in guiding the surgical management of renal tumors remains to be defined. Laparoscopic partial nephrectomy is emerging as an attractive approach for selected renal masses. Intraoperative use of ultrasound, cold-scissor parenchymal transection, embolization, and hilar clamping to achieve a bloodless operative field with clear visibility, may minimize the risk of positive margins during partial nephrectomy.

Flexible ureteroscopy and laser lithotripsy for single intrarenal stones 2 cm or greater--is this the new frontier?

PURPOSE: Percutaneous nephrolithotomy has been the standard of care for intrarenal calculi greater than 2 cm. Flexible ureteroscopy with holmium laser lithotripsy is a minimally invasive treatment modality that is able to treat large intrarenal calculi with the potential to decrease morbidity, while maintaining a high level of efficacy. MATERIALS AND METHODS: A total of 15 patients with a single intrarenal calculus 2 cm or greater were treated with retrograde ureteroscopic nephrolithotripsy. Lithotripsy was performed with a 7.2Fr flexible ureteroscope and 200 micron laser fiber. The stone-free rate was defined as the absence of any stones in the kidney or residual stone fragments less than 1 mm, which is too small to be extracted with a basket or a grasper. All patients underwent followup ureteroscopy within 15 days after the last procedure and renal ultrasound 30 days after the last treatment. RESULTS: There were a total of 15 intrarenal calculi 20 to 25 mm (mean 22) in diameter. The mean number of procedures was 2.3 (range 2 to 4). The overall stone-free rate was 93.3%. One patient (6.6%) had a residual 5 mm stone fragment in the lower pole of the kidney, which was followed expectantly for 2 years with no change in size. There were no major complications. There were 3 minor complications (20%), including 1 emergency room visit for fever and pain, and 2 cases of gross hematuria. All cases were performed on an outpatient basis. CONCLUSIONS: In select patients with a single intrarenal calculus 2 cm or greater small diameter flexible ureteroscopy with holmium laser lithotripsy may represent an alternative therapy to standard percutaneous nephrolithotomy with acceptable efficacy and low morbidity.

In vivo efficacy of laparoscopic assisted percutaneous renal cryotherapy: evidence based guidelines for the practicing urologist.

PURPOSE: The treatment of small renal tumors continues to evolve in parallel with advances in ablative technology. We compared the lesion geometry of 3, 17 gauge cryoneedles to determine the most effective distance and configuration of the cryoneedles in an in vivo porcine kidney model. MATERIALS AND METHODS: Argon gas based renal cryoablation was performed in 6 pigs using a laparoscopically assisted percutaneous approach. Cryoablation using a single cryoneedle and a template of 3 cryoneedles with various ice ball shapes, including elliptical, bulb-shaped and standard 17 gauge cryoneedles (Galil Medical, Plymouth Meadow, Pennsylvania) was performed in 3 pigs. Three additional pigs underwent renal cryoablation using elliptical cryoneedles in 3 triangular template configurations with the cryoneedles spaced 1, 1.5 and 2 cm apart, respectively. The animals were sacrificed a minimum of 2 weeks following treatment. RESULTS: Elliptical cryoneedles achieved the largest area of necrosis when used in single and template configurations. When used in a template configuration of 3 needles 1, 1.5 and 2 cm apart from each other the calculated volume of necrosis was 4.3 x 4.5 x 2.5, 4.9 x 4.1 x 2.5 and 4.0 x 4.5 x 2.5 cm, respectively. CONCLUSIONS: Using a single 17 gauge cryoneedle is inadequate for treating most small renal tumors. Cryoneedles with an elliptical ice ball are most effective for achieving consistent and reliable tissue destruction. The 1.5 cm template configuration generated the largest area of necrosis. Our data suggest that with the current technology renal cryoablation should be limited to lesions not greater than 4 cm.

Laparoscopic heminephrectomy for upper-pole moiety in children using a 3-mm laparoscope and instruments.

PURPOSE: We report three cases of laparoscopic heminephrectomy in infants using a 3-mm laparoscope and instruments. To our knowledge, this is the first pediatric heminephrectomy series reported in the literature that utilized these small instruments. PATIENTS AND METHODS: Three pediatric patients underwent laparoscopic heminephrectomy for an upper-pole moiety in a duplicated collecting system with 3-mm laparoscopic ports and a 3-mm Storz 30 degrees laparoscope. RESULTS: All three cases were completed laparoscopically with total times of 120, 135, and 160 minutes. There were no intraoperative complications, and there was minimal blood loss. The optics of the laparoscope provided visibility and illumination similar to those available with larger-diameter laparoscopes. Two patients were discharged approximately 1 day postoperatively. The third patient required intravenous antibiotics to treat a urinary-tract infection and was discharged home 4 days postoperatively. All three patients had recovered fully by 2 weeks. CONCLUSION: The 3-mm laparoscope provides excellent visibility and illumination for performing heminephrectomy in the pediatric population. In addition, the 3-mm instruments provide excellent tissue handling, similar to that of the 5-mm tools.