-
[show abstract]
[hide abstract]
ABSTRACT: Introduction: Extended warm ischemia time during partial nephrectomy leads to considerable renal injury. Using a rat model of renal ischemia, we examined the ability of a unique renoprotective cocktail to ameliorate warm ischemia-reperfusion injury and extend warm ischemia time. Materials and Methods: A warm renal ischemia model was developed using Sprague-Dawley rats, clamping the left renal artery for 40, 50, 60 and 70 minutes, followed by 48 hours of reperfusion. An improved renoprotective cocktail referred to as I-GPM (a mixture of specific renoprotective growth factors, porphyrins, and mitochondria protecting amino acids) was administered -24 hours, 0 hours and +24 hours after surgery. At 48 hours, both kidneys were harvested and examined with hematoxylin-eosin and periodic acid-Schiff (PAS) stains for the analysis of renal tubular necrosis. Creatinine, protein, and gene expression levels were also analyzed to evaluate several ischemia-specific and anti-oxidant response markers. Results: I-GPM treated kidneys showed significant reversal of morphological changes and a significant reduction in specific ischemic markers lipocalin-2, galectin-3, GRP-78 and HMGB1 as compared to ischemic controls. These experiments also showed an upregulation of the stress response protein HSP-70 as well as the phosphorylated active form of the transcription factor HSF-1. Additionally, quantitative RT-PCR analyses revealed a robust upregulation of several antioxidant pathway response genes in I-GPM treated animals. Conclusions: By histopathologic and several molecular measures, our unique renoprotective cocktail mitigated ischemia-reperfusion injury. Our cocktail minimized oxidative stress in an ischemic kidney rat model while at the same time protecting the global parenchymal function during extended periods of ischemia.
Journal of endourology / Endourological Society 10/2012; · 1.75 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Large upper tract urinary calculi, greater than 2 cm, have historically been treated with percutaneous nephrostolithotomy. In general, there has been a growing interest in employing retrograde, flexible ureteroscopy and laser lithotripsy in select patients who are either poor medical candidates for percutaneous lithotripsy or who may prefer a less invasive intervention. Properly selecting patients for this approach, designing specific treatments based on complex stone presentation and offering general information with regard to long-term outcomes and surgical risks have historically been based on results from small, multicentre series lacking uniformity of technique and long-term outcomes. Our initial multicentre experience employing ureteroscopic techniques to treat large upper urinary tract calculi was presented in 1998. This current work represented the largest single-centre experience, accrued prospectively over 10 years, where there was uniformity of technique and treatment algorithms. This study frames an argument for retrograde ureteroscopic lithotripsy not only in those who are at high risk for percutaneous nephrostolithotomy but in all who present with large, non-infected stone burdens. OBJECTIVE: • To define the safety and efficacy of retrograde ureteroscopic lithotripsy in treating large, non-infectious intrarenal and proximal ureteral stone burdens. PATIENTS AND METHODS: • Between 2000 and 2011, 145 patients with 164 large (2 cm or greater in diameter on standard imaging) non-infectious upper intrarenal and proximal ureteral calculi were chosen for retrograde ureteroscopic lithotripsy. • Patients were treated with small diameter flexible fibre-optic ureteroscopes and holmium laser lithotripsy by a single surgeon. • Second-look ureteroscopy was performed in patients with the largest calculi in whom there was a high index of suspicion of significant residual fragments. • Stone clearance was defined as no fragments or a single fragment less than or equal to 4 mm in diameter on standard radiograph and sonography at 3-month follow-up. RESULTS: • Our study included 103 male patients and 42 female patients with an average age of 55 years (range 16-86 years) and a mean stone diameter of 29 mm (range 20-70 mm) including 36 partial staghorn stone burdens (mean diameter 37 mm). Overall, 266 ureteroscopies were performed on 164 stone burdens (1.6 procedures per stone burden), clearing 143 stone burdens (87%). • The highest clearance rates were observed for proximal ureteral (97%) and renal pelvic (94%) stones, while the lowest clearance rates were observed for lower pole (83%) and staghorn calculi (81%). • Three patients required subsequent percutaneous therapy due to infectious material encountered at the time of ureteroscopy or inaccessible stone burdens secondary to infundibular stenosis. • There were five minor postoperative complications, including four fevers and one patient with gross haematuria and clot retention, with no major intraoperative complications. CONCLUSIONS: • In select patients, large, complex, metabolic upper urinary tract calculi can be treated safely and efficiently with retrograde ureteroscopic techniques. • Staged, retrograde, flexible ureteroscopy is an alternative to percutaneous therapy with acceptable efficacy and low morbidity.
BJU International 07/2012; · 2.84 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Upper urinary tract urothelial carcinomas (UTUC) have historically been treated with radical, extirpative surgery, primarily nephroureterectomy with bladder-cuff excision. In general, there has been growing interest in renal preservation, as evidenced by the broadening application of nephron-sparing surgery for renal parenchymal tumours. Beyond imperative reasons such as tumour in a solitary kidney, bilateral disease, or comorbidities preventing radical surgery, there is a growing role for endoscopic management of upper tract tumours. The aim has been to obtain similar oncological results to those of extirpative surgery, while preserving long-term renal function. Properly selecting patients for these therapies, designing specific treatments based on a complex presentation, and general information with regard to outcomes and risks for patient counselling have been based historically on results from relatively small series without long-term follow-up. This study reflects all patients with UTUC treated by a single tertiary referral surgeon, accrued prospectively over 15 years using the same surgical techniques and treatment algorithms throughout the entire study period, with 10-year survival data. The consecutively accrued nature and size of the study groups, uniformity in treatments, statistical review and long-term follow-up provide baseline oncological data that could help frame future study. OBJECTIVE: • To present long-term oncological outcomes of all patients treated surgically for upper urinary tract urothelial carcinoma (UTUC) over a 15-year period. PATIENTS AND METHODS: • All patients (N= 160) treated from January 1996 to August 2011 were prospectively studied and placed into three distinct groups after initial diagnostic ureteroscopy (URS): Group 1: low grade lesions treated with URS (n= 66); Group 2: high grade lesions palliatively treated with URS (n= 16); and Group 3: extirpative surgery (nephroureterectomy [NU]; n= 80). • Statistical analysis was performed using Kaplan-Meier methodology to calculate overall (OS), cancer-specific (CSS) and metastasis-free survival (MFS). RESULTS: • The median patient age at presentation was 73 years, and the mean (range) follow-up time was 38.2 (1-185) months. At initial diagnostic URS, 71 (44.4%) patients presented with high grade and 89 (55.6%) patients presented with low grade disease. • The 2-, 5- and 10-year CSS rates were 98, 87 and 81% for patients with low grade disease, and 97, 87 and 78% for patients treated with URS (Group 1), not significantly different from those patients with low grade disease treated with NU (Group 3), (P= 0.54). • Of the patients treated with URS for low grade disease, 10 (15.2%) progressed to high grade disease at a mean time of 38.5 months. • Patients with high grade disease treated with NU had a 2-, 5-, and 10-year CSS of 70, 53 and 38%, with a MFS of 55, 45 and 35%. • Median survival of patients with high grade disease treated with palliative URS was 29.2 months with a 2-year OS of 54%. • On multivariate analysis only high grade lesion on initial presentation was found to be a significant factor (P < 0.001; hazard ratio = 7.27). CONCLUSIONS: • Grade is the most significant predictor of OS and CSS in those with UTUC, regardless of treatment method. • Ureteroscopic and extirpative therapy are acceptable options for those with low grade disease showing excellent long-term CSS. • Extirpative therapy was found to result in relatively poor long-term CSS in patients with high grade disease, underscoring the need for adjuvant or neoadjuvant therapies.
BJU International 03/2012; · 2.84 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Extended warm ischemia during partial nephrectomy can lead to considerable renal injury. Using a rat model of renal ischemia we examined the ability of a unique renoprotective cocktail to ameliorate warm ischemia-reperfusion injury.
A warm renal ischemia model was developed using 60 Sprague-Dawley® rats. The left renal artery was clamped for 40 minutes, followed by 48 hours of reperfusion. A renoprotective cocktail of a mixture of specific growth factors, mitochondria protecting biochemicals and Manganese-Porphyrin (MnTnHex-2-PyP(5+)) was given intramuscularly at -24, 0 and 24 hours after surgery. At 48 hours the 2 kidneys were harvested and examined with hematoxylin and eosin, and periodic acid-Schiff stains. Protein and gene expression were also analyzed to determine ischemia markers and the antioxidant response.
Compared to ischemic controls, kidneys treated with the renoprotective cocktail showed significant reversal of morphological changes and a significant decrease in the specific ischemic markers lipocalin-2, mucin-1 and galectin-3. Quantitative reverse transcriptase-polymerase chain reaction revealed up-regulation of several antioxidant genes in treated animals.
According to histopathological and several molecular measures our unique renoprotective cocktail mitigated ischemia-reperfusion injury.
The Journal of urology 12/2011; 186(6):2448-54. · 4.02 Impact Factor
-
Michael Grasso
Urology 10/2010; 76(4):881-2. · 2.43 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Endoscopic management of upper urinary tract transitional cell carcinoma has assumed an important role in diagnosis and treatment. The introduction of small diameter rigid and flexible ureteroscopes has permitted access to the upper tract. Biopsy techniques have been developed for accurate diagnosis, and the addition of lasers has given the urologists an excellent tool for treatment.
Medical literature available relative to the endoscopic laser treatment of upper tract neoplasms has been reviewed.
Ureteroscopic treatment has been characterized by good success with high recurrence rates, both in the upper tract and in the bladder. Bladder recurrence rates are similar to those seen after surgical treatment of upper tract tumors. Surveillance has been ureteroscopic since the other diagnostic options are inadequate. The holmium and neodymium:YAG lasers are the devices most commonly used now for the endoscopic treatment of upper tract tumors.
Ureteroscopic treatment of upper tract neoplasms usually with ablation and resection using the neodymium and holmium:YAG lasers is a current acceptable procedure. This should be considered as one of the options in tumor treatment.
World Journal of Urology 03/2010; 28(2):143-9. · 2.41 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: With the advent of improved diagnostic and imaging techniques, it is now possible to detect renal cancers in their very early stages, when they are still present as small renal masses. In these situations, use of laparoscopic partial nephrectomy (LPN) techniques are indicated and have gained acceptance in major medical institutions worldwide, offering comparable oncological outcomes and improving quality of life in the patient when contrasted with open nephrectomy procedures. However, a complication that may occur during or after this surgery is the possibility of compromising renal function, as a result of extended ischemia times of more than 30 min. We have undertaken a systematic study of the potential of several agents that may enhance renal parenchymal preservation without causing unwanted renal dysfunction as a result of enhanced ischemia times. In this study, we have evaluated the potential of one such agent under study, namely hydralazine, which was shown earlier to enhance hypoxia inducible factor-1α (HIF-1α) levels in experimental animal systems. Our aim was to determine whether enhanced levels of HIF-1α via pre-treatment with hydralazine had a reno-protective effect after ischemic injury.
Rats were injected with hydralazine or saline for 5 days prior to right nephrectomy and 40 min of cross-clamping of the left renal pedicle. Ischemic damage was monitored via serum chemistry and renal pathology.
In our system, we found that hydralazine pre-treatment, even though it enhanced HIF-1α levels in the kidney, it also increased serum creatinine and worsened the morphological damage to the renal tubules in the ischemic kidney.
We conclude that even though this agent was described as a powerful inhibitor of prolyl hydroxylases, enhancing the levels of HIF-1α, it should be approached with caution when it is considered to enhance warm ischemia time and minimize the renal damage subsequent to LPN.
World Journal of Urology 06/2009; 27(6):817-23. · 2.41 Impact Factor
-
Michael Grasso
[show abstract]
[hide abstract]
ABSTRACT: Upper urinary tract urothelial tumors reflect a small but growing number of urologic malignancies. The application of progressive endoscopic therapies including ureteroscopic and percutaneous nephroscopic resection and topical chemotherapy have found success, defined as the preservation of the renal unit without malignant progression, in those with low grade lesions. Careful and meticulous diagnostic endoscopy with tissue sampling and cytologic evaluation is key to directing treatment and counseling patients with regard to the risk of recurrence and progression. It is the population with a low grade lesion and negative cytology that are most commonly selected for endsoscopic resection. Those with high grade lesions who opt for endoscopic resection are counseled that this therapy is palliative and can often control local symptoms but is infrequently curative. Surveillance endoscopy post endoscopic resection and topical chemotherapy is essential. With growing surgical experience and improved instrumentation, the complications associated with these and other endoscopic procedures is acceptably low.
Archivos españoles de urología 12/2008; 61(9):1070-9.
-
[show abstract]
[hide abstract]
ABSTRACT: Retrograde ureteroscopy has recently gained a broadened indication for use from diagnostic to a variety of complex minimally invasive therapies. This review aims to look at the recent advances in the instrumentation and accessories, the widened indications of its use, surgical techniques and complications. With minimization of ureteroscopic instruments manufacturers are challenged to develop new, smaller and sturdier instruments that all will also survive the rigors of surgical therapy.
Indian Journal of Urology 11/2008; 24(4):532-7.
-
[show abstract]
[hide abstract]
ABSTRACT: Fluorescence in-situ hybridization (FISH) assay has been approved by the U.S. Food and Drug Administration for the detection of recurrent transitional-cell carcinoma (TCC) of the bladder and in the initial workup of hematuria. In this study, we retrospectively reviewed our initial 94 FISH specimens taken from patients monitored for upper-tract TCC.
Between 2004 and 2007, 43 patients had one or more FISH assays performed as part of the workup and management of upper-tract TCC. Of 94 specimens sent for FISH analysis, 25 voided specimens collected at an outpatient encounter and 40 specimens taken as a bladder wash or selective upper-tract washing under anesthesia were followed by upper-tract endoscopy. The sensitivity and specificity of the FISH assay for detecting urothelial lesions in this population were calculated and compared with cytology specimens from the same sources.
Overall sensitivity of FISH in the detection of TCC in this population was 52%, compared with 26% for urinary cytology. Both FISH and cytology showed superior sensitivity for high-grade (79% and 50%, respectively) nu low-grade tumors (41% and 12%, respectively). Selective upper-tract washings were more sensitive and specific for upper-tract TCC than bladder washings or voided specimens.
While the sensitivity of FISH for upper-tract TCC parallels its performance in bladder cancer, the preponderance of low-grade, recurrent disease in the population undergoing surveillance and minimally invasive therapy for upper-tract TCC may limit its usefulness in this setting. Until a high-sensitivity marker for low-grade urothelial lesions is developed, the surveillance of upper-tract TCC will continue to require vigilant direct visual inspection.
Journal of endourology / Endourological Society 07/2008; 22(6):1371-4. · 1.75 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The diagnosis of medullary sponge kidney traditionally was established by means of intravenous pyelography. Beginning in the mid-1990s, intravenous pyelography rapidly was supplanted by computed axial tomography as the preferred imaging study for evaluating patients with renal stone disease. Conventional computed tomographic imaging has not been satisfactory for diagnosing medullary sponge kidney. The introduction of multidetector-row computed tomography in 1999 allowed radiologists to acquire images composed of elements allowing the creation of high-resolution 3-dimensional displays. Computed tomographic urography is an imaging technique that provides both cross-sectional displays and images of the contrast-filled renal collecting systems, ureters, and urinary bladder that are the equivalent of intravenous pyelography. We report a case of medullary sponge kidney diagnosed by means of 3-dimensional multidetector-row computed tomographic urography.
American Journal of Kidney Diseases 08/2007; 50(1):146-50. · 5.43 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The introduction of a new generation of flexible ureteroscopes significantly advanced the therapeutic and diagnostic efficacy of the instrument, allowing greater access to all aspects of the upper urinary tract and facilitating wireless ureteroscopy.
Four hundred sixty consecutive upper urinary-tract procedures were performed utilizing the 7.5F actively deflectable, flexible ureteroscope. A prospective database of these procedures was maintained. The indications, access technique, complications, success rate of stone treatment, and access to lower-pole calices were evaluated. The accumulated clinical data were compared with a published database of 1000 consecutive flexible ureteroscopies.
A stent was in place or had recently been in place in 108 of the procedures (24%). Of the remaining 352 flexible ureteroscopic procedures, only 11% (52) required any form of ureteral dilation to facilitate ureteral access. Two hundred twenty seven procedures were performed in which no guidewire was required to place the flexible endoscope in the upper urinary tract (i.e., "wireless" ureteroscopy).
Wireless no-touch flexible ureteroscopy with the new flexible instruments is a feasible and safe technique for diagnostic and therapeutic procedures in most patients, irrespective of the location of the pathology, including the distal ureter. These ureteroscopes, with their exaggerated deflection, are ushering in a new era of endoscopic treatment of the upper urinary tract. Greater instrument deflectability and control can lead to shorter procedures and fewer treatment failures.
Journal of Endourology 09/2006; 20(8):552-5. · 1.85 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Traditionally, nephroureterectomy has been the treatment of choice for transitional cell carcinoma of the upper urinary tract. In an effort to preserve renal function, conservative therapy has evolved from complex open surgery to minimally invasive ureteroscopic therapy. Considering the relatively recent emergence of ureteroscopic therapy, a review of technical considerations and treatment outcome is timely.
There is emerging evidence that ureteroscopic treatment of low grade upper tract lesions provides an acceptable oncologic result while preserving functioning renal parenchyma. In patients with low grade upper tract urothelial lesions, progression is rarely reported. Ureteroscopy has for over a decade been the premier diagnostic tool, with the actively deflectable flexible instrument being employed to map the entire intrarenal collecting system. Improvements in instrumentation and refinement in technique have broadened the application of the ureteroscope in treating upper urinary tract urothelial tumors.
For low grade lesions, which make up more than 50% of all presentations, ureteroscopic management has proven efficacious. As with similar grade lesions in the bladder, these patients require careful, consistent, and often lifelong follow up as many will develop recurrent lesions throughout the urothelium. Here too, ureteroscopy has a central role in surveillance.
Current Opinion in Urology 04/2005; 15(2):89-93. · 2.59 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To determine the effect of cystine-binding thiol drugs (CBTD) on urinary cystine capacity in patients with cystinuria.
Seven cystinuric patients performed two sets of urine collections while on and off CBTD while controlling for all other variables: diet and fluid and alkali intake. They monitored and recorded their diet for 3 days and performed urine collections on days 2 and 3. They then stopped the CBTD for 7 days. On days 8, 9, and 10, they replicated their diets of days 1 through 3 and performed two more urine collections on days 9 and 10. Two patients took D-penicillamine, four took tiopronin, and one took tiopronin and captopril. The cystine capacity was determined, and the values obtained when the patient was on and off the CBTD were compared to determine whether CBTDs affect urinary cystine capacity. To measure the cystine capacity, we used a solid-phase assay in which cystine crystals are added to the urine and incubated for 48 hours. The crystals are spun down and resolubilized in high-pH buffer, and the amount of cystine in the crystals is calculated. The solid phase will take up cystine from urine (negative cystine capacity) that is supersaturated and give up cystine to an undersaturated urine (positive cystine capacity).
All seven patients had significant improvement in urinary cystine capacity on CBTDs. The mean cystine capacity off CBTD was -130.6 +/- 280.8, while the value during CBTD use was 43.1 +/- 131.2 (P < 0.05). On CBTDs, two patients still had negative values, but both had important improvements. The mean urinary volumes were similar on and off CBTD, indicating adequate and similar fluid intake. Urine pH values and urinary excretion of sodium and urea also were comparable, indicating consistency of citrate intake and diet.
Our results demonstrate that CBTDs lower the urinary supersaturation of cystine, as shown by a less-negative or more-positive cystine capacity. Cystine capacity can be measured directly, even in the presence of CBTDs. The value of this measurement lies in the potential to monitor the response to the drug, prescribe the minimum effective dose, and potentially decrease the adverse effects often associated with CBTDs.
Journal of Endourology 04/2005; 19(3):429-32. · 1.85 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Pneumothorax is a rare but known complication of adult urological laparoscopic surgery and has been described occasionally in children as well. The etiologies for pneumothorax during such procedures are discussed as is the management of pneumothorax in this setting. We investigate the occurrence of pneumothorax during laparoscopic pediatric urological procedures in children.
Pneumothorax developed during urological laparoscopic procedures in 4 pediatric patients (3 females, 1 male). Patient age ranged from 8 months to 11 years (mean 5.4 years). Laparoscopic surgical procedures performed included right upper pole partial nephrectomy, left upper pole partial nephroureterectomy, removal of left multicystic dysplastic kidney and bilateral Cohen reimplantation of ureters. Procedures were performed with a maximum insufflation pressure of 15 mm Hg. During the same time period as these four cases, a total of 285 laparoscopic urologic procedures were performed at our institution.
Pneumothorax was suspected due to decreased oxygen saturations, subcutaneous emphysema, increased respiratory effort and decreased chest lung sounds unilaterally. Pneumothorax was confirmed with chest x-rays. Operative time ranged from 171 to 249 minutes (mean 199.5). Duration of surgery before pneumothorax developed ranged from 75 to 239 minutes (mean 176, median 168). Conservative management of pneumothorax was used in 3 patients and a pigtail chest tube was used in 1. In all cases the estimated blood loss was minimal.
Urologists performing laparoscopy in children should be aware of the possibility of a pneumothorax developing during the procedure. Evaluation for decrease in O2 saturation should include a search for pneumothorax in these patients. Close observation generally suffices for management.
The Journal of Urology 04/2004; 171(3):1256-8; discussion 1258-9. · 3.75 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The difficulty in managing complex biliary tract calculi is exemplified in patients with primary intrahepatic calculi. Standard surgical and endoscopic approaches often fail to clear calculi in these patients who have recurrent episodes of cholangitis. The success of the holmium laser for urologic calculi led us to adapt treatment strategies for primary and secondary biliary tract calculi where standard treatments had been unsuccessful. Our goals were to remove all calculi, prevent recurrent sepsis, and preserve hepatic parenchyma. Thirty-six patients with complex biliary calculi were treated. After sepsis was controlled and the extent of calculi was evaluated, appropriate access to and drainage of the biliary tract was achieved. Holmium laser lithotripsy was performed under video guidance using flexible choledochoscopes and a 200 micro laser fiber generating 0.6 to 1.0 joules at frequencies of 6 to 10 Hz. Lithotripsy procedures were repeated until cholangiography and cholangioscopy confirmed the clearance of calculi. Twenty-two patients of Asian descent with primary intrahepatic calculi and 14 patients with secondary intrahepatic calculi were treated. Access to the biliary tract could be accomplished through percutaneous catheter tracts, T-tube tracts, or the cystic duct during laparoscopic cholecystectomy. Biliary drainage was by biliary enteric anastomosis or endoscopic sphincterotomy. Complete stone clearance required an average of 3.9 procedures (range 1 to 15) for patients with primary intrahepatic calculi and 2.6 procedures (range 1 to 10) for patients with secondary intrahepatic calculi regardless of stone composition. No patient required hepatic resection and no complications or deaths were attributed to the holmium laser. Clearance of calculi can reliably and safely be achieved with a holmium laser regardless of stone composition or location while preserving hepatic parenchyma and preventing recurrent sepsis.
Journal of Gastrointestinal Surgery 03/2004; 8(2):191-9. · 2.83 Impact Factor
