Commentary

Adoption and diffusion of new surgical technology is the lifeblood of our profession. Changes in our urologic practices, as we all know, are never easy and may be influenced by many social, economic and professional factors. Change also requires of the surgeon a considerable amount of effort and energy to determine if there is sufficient amount of objective data available to demonstrate that the proposed change(s) will improve patient care. The first laparoscopic radical nephrectomy was performed in June 1990. As the surgeons involved in those early cases will attest, these were long, laborious and frustrating cases. Wilson describes the characteristics that influence the adoption of new technology by surgeons.¹ The initial “characteristics” of laparoscopic renal surgery did not support early adoption. It was not a simple modification of an existing procedure; it was not easily learnt; the volume of cases was unknown or limited; it was not low-cost for surgeons to learn and perfect the procedure; it was more expensive initially than the open surgical approach; the initial laparoscopic tools were somewhat primitive and in evolution.

What were the factors that kept laparoscopic radical nephrectomy from becoming a “discredited technology”? Initial postoperative results were impressive with respect to analgesic requirements, decreased nursing requirements and shorter hospitalization and convalescence. The big appeal for the medically naïve patient certainly was the improved cosmetic incisional appearance and attraction of “band-aid surgery.” Finally, the pioneers of urologic laparoscopic surgery were a group of very stubborn and determined individuals who believed strongly in what they were pursuing. They could see the “light at the end of the tunnel,” ahead of the rest of us.

As the article by Filson and colleagues demonstrates, for almost a decade (1990–2000), laparoscopic radical nephrectomy was rarely performed. It is interesting to again see this in graph form and this is supported by Miller and colleagues, who describe “Trends in the Diffusion of Laparoscopic Nephrectomy.”² The so called “tipping point” was in the year 2000–2001 where the use of this operation for treating renal cancer increased significantly. Between 1990 and 2000, the laparoscopic equipment improved, laparoscopic innovators could develop sufficient skills and approaches to make the operation faster and safer, and we became able to teach these skills to younger and interested urologists and residents in training. Malcolm Gladwell beautifully describes social changes—at about 20% adoption, the speed of diffusion significantly increases.³ The same can be said for laparoscopic radical nephrectomy.

The adoption of partial nephrectomy for smaller renal masses (clinical T1) continues to lag behind what one would hope or expect. As is described in the article by Abouassaly and colleagues, even in patients with the strongest indications for partial nephrectomy (diabetes and hypertension), this technique is underutilized. There is now abundant, long-term data available to demonstrate that partial nephrectomy yields equal oncologic results to radical nephrectomy for renal cell carcinoma.⁴ There is also abundant long-term data to show that diabetes mellitus, followed by hypertension, are the two most frequent causes of end-stage renal disease.⁵ In 2009 the American Urological Association published guidelines for the treatment of T1 renal tumors.⁶ The consensus was that partial nephrectomy should be the procedure of choice, unless tumor location or other associated surgical or medical conditions prevent this approach.

Returning to the articles by Wilson¹, Miller et al², and the psychosocial overview of Gladwell,³ we know that a partial nephrectomy, whether done via open or laparoscopic approach, is not necessarily an easy procedure compared to a radical nephrectomy. The perioperative complications for partial nephrectomy may be higher, certainly for the laparoscopic approach, and the time requirements and financial gains may not be in the favor of the surgeon to learn and adeptly adopt this procedure. Finally, the surgeon might mentally justify that the cancer is being effectively eradicated by a radical nephrectomy and so “we'll worry about renal insufficiency down the road and it may never be a problem in this patient.” Clearly it will become a problem, as the data shows. In fact, we may be eradicating the cancer today but dooming the patient to death from complications of chronic renal failure.

It is my belief that we are now at a “tipping point” with respect to adopting partial nephrectomy. The technique is practiced and taught extensively in most urologic residency programs. Despite the robotic surgery naysayers, robotic partial nephrectomy is a viable procedure and is not going to go away. If anything, it has and will allow more surgeons to perform partial nephrectomy in a safe and effective fashion. The data is still evolving. The future decade, as in the past, will be exciting for urologic renal surgery.

References

1. Wilson CB. Adoption of new surgical technology. BMJ 2006;332:112–114.

2. Miller DC, Wei JT, Dunn RL, et al. Research letter – trends in the diffusion of laparoscopic nephrectomy. JAMA 2006;295:2480–2482.

3. Gladwell M. The Tipping Point: How Little Things Can Make a Big Difference. New York: Little, Brown and Co., 2000.

4. Fergany AF, Hafez KS, Novick, AC. Long-term results of nephron sparing surgery for localized renal cell carcinoma: 10-year follow-up. J Urol 2000;163:442–445.

5. US Renal Data System. USRDS 2007 Annual Data Report: Atlas of End-Stage Renal Disease in the United States. Minneapolis, MN, USA: National Institutes of Health, 2007.

6. Campbell SC, Novick, AC, Belldegrun, A, et al. Guidelines for management of the clinical T1 renal mass. J Urol 2009;182:1271–1279.

Howard N. Winfield, M.D.

Commentary

This retrospective cohort study examined the utility of preoperative stent placement in patients undergoing ureteroscopic treatment of urinary calculi. Patients who had a preoperative stent placed were compared to those who did not; they were not randomized. It was the intention of the authors to remove all calculi >2 mm at the time of ureteroscopy. The same group has shown that preoperative stenting decreased operative time and re-treatment rates for those patients with stones larger than 1 cm.¹ Others have shown similar results.² The current study is effectively the next step in the evaluation process of preoperative stenting before ureteroscopic treatment—the cost-effectiveness analysis (including a sensitivity analysis to evaluate the cost model used). There were 45 patients who were pre-stented prior to ureteroscopy and 59 who were not. The demographics and stone characteristics and overall stone clearance were not significantly different between the two cohorts, though there was a trend toward improved stone clearance with preoperative stenting. The mean preoperative duration of the stent was 19.5 days. The authors found that the differences in total healthcare costs between the two cohorts depended upon the size of the stone burden. The costs favored preoperative stenting in patients with a stone burden >1cm, where there was greater operating time advantage when removing stone fragments. The costs favored not preoperatively stenting in those with a stone burden <1 cm when this time advantage would be less significant. The cost advantage in patients with stone burden >1 cm correlated strongly with OR time (r = 0.993).

This study interests me for a number of reasons. At first glance, it seems to make sense that preoperative stenting would improve the operative time for patients with large stones. However, the only real technical difference between the two cohorts is the use of a larger ureteral access sheath in the prestented cohort. Does this alone really account for the shorter operative time (287 vs 158 minutes) in those with stones >1 cm? What other factors about pre-stenting might decrease the operative time? Is there more room to work, or is the collecting system less hydronephrotic, improving access to all areas of the intrarenal collecting system? Is visibility better? Since one cannot be blinded to the presence of a preoperatively placed stent, is some of the improvement in operative time a result of changed behavior in the surgeon (more confident and deliberate technique)? For those urologists who simply ablate and remove fragment stones ureteroscopically and do not routinely attempt to ureteroscopically remove all fragments, there would seem little advantage to pre-stenting, as a ureteral access sheath is not needed. However, if these other potential factors are part of the reason for the improved OR time, perhaps pre-stenting would be cost effective for patients with large stones even in this treatment strategy.

References

1. Chu L, Sternberg KM, Averch TD. Preoperative stenting decreases operative time and reoperative rates of ureteroscopy. J Endourol 2011;25:751–754.

2. Shields JM, Bird VG, Graves R, Gómez-Marín O. Impact of preoperative ureteral stenting on outcome of ureteroscopic treatment for urinary lithiasis. J Urol 2009;182:2768–2774.

Michael J. Conlin, M.D.

Combining imaging and ureteroscopy variables in a preoperative multivariable model for prediction of muscle-invasive and non-organ confined disease in patients with upper tract urothelial carcinoma. Favaretto RL, Shariat SF, Savage C, Godoy G, Chade DC, Kaag M, Bochner BH, Coleman J, Dalbagni G, Urology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center Department of Urology and Division of Medical Oncology, Weill Cornell Medical College, New York-Presbyterian Hospital Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY.

BJU Int 2011; Jun 1 [epub ahead of print]

Study Type: Diagnostic (exploratory cohort)

Level of Evidence: 2b

What's known on the subject? and What does the study add? Improved patient selection for conservative management, neoadjuvant chemotherapy, and/or extended lymphadenectomy is urgently needed. We developed a highly accurate preoperative model to predict muscle-invasive and non-organ-confined upper tract urothelial carcinoma based on standard imaging and ureteroscopy features.

Objective:

• To create a preoperative multivariable model to identify patients at risk of muscle-invasive (pT2+) upper tract urothelial carcinoma (UTUC) and/or non-organ confined (pT3+ or N+) UTUC (NOC-UTUC) who potentially could benefit from radical nephroureterectomy (RNU), neoadjuvant chemotherapy and/or an extended lymph node dissection.

Patients and Methods:

• We retrospectively analysed data from 324 consecutive patients treated with RNU between 1995 and 2008 at a tertiary cancer centre.

Results:

• The median follow-up for patients without disease recurrence or death was 4.2 years.

Conclusions:

• We designed a preoperative prediction model for pT2+ and NOC-UTUC, based on readily available imaging and ureteroscopic grade.

© 2011 The Authors. BJU International © 2011 BJU International.

DOI: 10.1111/j.1464-410X.2011.10288.x

Commentary

This is a review of the authors' experience in treating patients with upper tract urothelial carcinoma (UTUC) in an attempt to develop a multivariable model to determine those patients who will develop muscle invasive or non-organ confined disease, who would be better served by nephroureterectomy rather than ureteroscopic management. If these patients at risk of advanced disease could be reliably determined preoperatively using this model, they may also benefit from neoadjuvant chemotherapy and extended lymph node dissection. The authors present the results of their review of 274 UTUC patients who were treated with nephroureterectomy. The factors reviewed for the logistic regression model included findings on imaging (hydronephrosis and appearance of local invasion), and ureteroscopy (location and tumor grade). Other authors have shown a strong correlation between ureteroscopic grade and final histologic stage.¹ About half of the patients in this study were found to have hydronephrosis and 15% had evidence of local invasion on imaging. Following nephroureterectomy, 49% were found to have muscle invasion, and 30% had non-organ confined disease. The appearance of local invasion on imaging and high grade tumor on ureteroscopy were each predictors of advanced disease. Tumor location and hydronephrosis on imaging were not significant factors. In the predictive model used, patients with high grade tumor on ureteroscopy and local invasion found on imaging have probabilities of 82% for muscle invasion and 76% for non-organ confined disease.

An advantage of this study is that each patient had a formal lymph node dissection at the time of their nephroureterectomy, and an extended dissection if locally advanced disease was detected. We can have some degree of certainty that any lymph node spread was detected. I would like to have seen the testing of tumor multifocality as a predictive factor in their model. It is not stated why this was not considered, or if it was tested and found not to be significant. Multifocality is associated with a higher recurrence rate in patients with transitional cell carcinoma, but it is less clear if it would be predictive of advanced disease in this population.

With increasing use of ureteroscopy in the treatment of upper tract transitional cell carcinoma, better tools to select appropriate patients for this treatment are critical. We have progressed from offering ureteroscopic treatment only to patients in whom nephroureterectomy is not a feasible choice due to medical comorbidities, to using it as an alternative to nephroureterectomy in otherwise healthy individuals.² As a result, our decision making has become more difficult. Many of these patients are elderly and have multiple comorbidities. Many have already had the contralateral kidney removed for the same problem, or have underlying renal insufficiency. Nephroureterectomy can result in dialysis for some of these patients, also a potentially life-threatening proposition. Can we safely continue to treat a patient ureteroscopically or should we remove the risk of tumor progression by removing the kidney? I have made the wrong decision both ways more than once. There is also a significant advantage to identifying patients preoperatively who would have more advanced disease, as they could receive neoadjuvant chemotherapy, and an extended lymph node dissection. The ability to administer neoadjuvant chemotherapy is particularly advantageous in this setting, given the important role of cis-platinum in the treatment of transitional cell carcinoma and potential development of renal insufficiency after nephroureterectomy preventing its use. The stakes are high in treating patients with this frequently lethal disease, and this study hopes to provide assistance in our management of these patients.

References

1. Keeley FX, Kulp DA, Bibbo M, et al. Diagnostic accuracy of ureteroscopic biopsy in upper tract transitional cell carcinoma. J Urol 1997;157:33–37.

2. Chen GL, Bagley DH. Ureteroscopic management of upper tract transitional cell carcinoma in patients with normal contralateral kidneys. J Urol 2000;164:1173–1176.

Michael J. Conlin, M.D.

Commentary

This is an excellent overview article which adequately addresses selected clinical cases that make percutaneous renal access and surgery more challenging. The strength of this article is that it summarizes, for the most part, reported techniques used to overcome specific challenges as well as how to avoid complications. The authors made specific references to calculi in kidneys with angiomyolipoma, stones in calyceal diverticulum, horseshoe kidneys, pelvic kidneys, hypermobile kidneys, morbid obese patients and full staghorn calculi. The concise writing in this article makes it an excellent resident teaching tool in percutaneous renal surgery, along with another excellent journal article that defines the various fluoroscopic techniques for percutaneous renal access.¹

Reference

1. Miller NL, Matlaga BR, Lingeman JE. Techniques for fluoroscopic percutaneous renal access. J Urol 2007;178:15–23.

Michael Y.C. Wong, M.B.B.S.

Image guided percutaneous probe ablation for renal tumors in 65 solitary kidneys: functional and oncological outcomes. Altunrende F, Autorino R, Hillyer S, Yang B, Laydner H, White MA, Khanna R, Isac W, Spana G, Stein RJ, Haber GP, O'Malley CM, Remer EM, Kaouk JH, Section of Laparoscopic and Robotic Surgery, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH.

J Urol 2011;186:35–41.

Purpose: We evaluated the oncological and functional outcomes of computerized tomography guided percutaneous cryotherapy or radio frequency ablation of kidney tumors in patients with a solitary kidney.

Materials and Methods: We reviewed the medical charts of patients with a solitary kidney who underwent percutaneous probe ablation for renal masses at our institution from April 2002 through March 2010. Followup consisted of computerized tomography or magnetic resonance imaging 1 day postoperatively, at 3, 6 and 12 months, and annually thereafter. Serum creatinine and estimated glomerular filtration rate were used to measure renal function. The cryotherapy and radio frequency ablation groups were compared for demographics, the 2-year actuarial survival rate and renal function.

Results: Overall 65 patients were included in this retrospective analysis, of whom 29 (44.6%) underwent cryotherapy and 36 (55.4%) underwent radio frequency ablation. Median followup was 15.1 (IQR 4.4 to 32.9) and 38.8 months (13.8 to 50.7), respectively. The 2 groups were comparable in median age, body mass index, American Society of Anesthesiologists score, tumor size and preoperative estimated glomerular filtration rate. The 3 primary treatment failures, including 1 after cryotherapy and 2 after radio frequency ablation, were successfully re-treated with thermal ablation. There were 14 recurrences after radio frequency ablation and 3 after cryotherapy. Two-year actuarial overall, cancer specific, recurrence-free and metastasis-free survival rates for cryotherapy vs radio frequency ablation were 89% vs 93%, 100% vs 96%, 69% vs 58% and 86% vs 91%, respectively. For each group no significant decrease in renal functional parameters was found at the latest followup visit.

Conclusions: Computerized tomography guided percutaneous probe ablation represents a safe treatment option in surgical patients at high risk with a solitary kidney. It provides low morbidity, acceptable short-term cancer control and minimal clinical impact on postoperative renal function.

Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Commentary

To my knowledge, this is the largest retrospective series (n = 65) reporting the comparative analysis of oncological and functional outcomes of CT-guided percutaneous cryotherapy (n = 29, 44.6%) vs RFA (n = 36, 55.4%) of two comparable groups of kidney tumors in solitary kidneys. This data suggests and reaffirms earlier reports¹ that cryotherapy results (at mean follow-up of 15.1 months) are more consistent and offer more reliable oncological outcome than RFA (at mean follow-up 38.8 months). The authors found that incomplete treatment and recurrent tumor rates were higher in the RFA group. The authors argue that this might be attributed to the fact that real-time imaging to monitor tumor destruction is not as reliable with RFA. There were no differences in overall cancer-free, recurrence-free and metastasis-free survival rates between the two modalities.

Along with earlier studies this paper shows that probe ablation techniques can be repeated more than once with limited effect on renal function and with minimal morbidity even in this high risk group of solitary kidneys.² An interesting issue in this series is the role of preoperative biopsy, obtained in two-thirds of the cases, raising the question of the value of preoperative histological diagnosis of small renal lesions with radiological suggestion of renal cell carcinoma. The limitations of this study include the selection biases inherent in a retrospective study, such as missing radiological films, which limit comparison of measureable radiological tumor features with other reported series.

This study affirms AUA guideline recommendations of probe ablation as a treatment option in selected patients with increased surgical risk and co-morbidities.³

References

1. Kutikov A, Kunkle DA, Uzzo RG. Focal therapy for kidney cancer: a systematic review, Curr Opin Urol 2009;19:148–153.

2. Raman JD, Raj GV, Lucas SM, et al. Renal functional outcomes for tumors in a solitary kidney managed by ablative or extirpative techniques. BJU Int 2010;105:496–500.

3. American Urological Association: Guideline for management of the clinical stage 1 renal mass. Available at http://www.auanet.org/content/media/renalmass09.pdf

Michael Y.C. Wong, M.B.B.S.

Commentary

The rapid propagation of shock wave technology has introduced a certain deficit in training in the proper delivery of shock waves, with a tendency to overlook the destructive power of shock waves and their potentially traumatic effects to the kidney and adjacent organs. Although the administration of shock wave generally is a safe procedure, it remains important that studies like this continue to draw the attention to possible side effects.

The retrospective study by Krambeck suggested an increased risk of diabetes mellitus (DM) following SWL of renal and proximal ureteral calculi.¹ This was supposedly due to shock wave energy damaging the pancreas.

The authors of the current prospective study correctly point out that in order to cause damage to the pancreas or any other organ adjacent to the kidney or the ureter, the shock waves need to directly impact these organs. A number of elements are important in this. First, there is the type of lithotripter used and, more specifically, focus size and the direction of coupling of the therapy head to the patient.

Most modern lithotripters have a smaller focus than the original Dornier HM3. The Storz Modulith SL20 used in this study has a focus size of 28 × 6 mm. It must be noted, however, that focus size increases slightly with increasing energy level. More importantly, there is still acoustic energy that may be sufficient to cause collateral damage beyond the published focus size. Lithotripter users should be aware of this so called “blast path.”

Another important element is the direction of coupling of the therapy head to the patient. In the Storz Modulith SL 20, the therapy head is coupled perpendicular to the dorsal region of the patient with the long axis of the cigar-shaped focus sagittal to the frontal plane of the patient. In this coupling mode, the risk of directly hitting the pancreas seems remote.

In lithotripters where the therapy head can also be coupled obliquely to the flank side of the patient, however, there may be an increased risk of directly hitting the pancreas in certain circumstances. In this coupling mode, lithotripter operators need to be very much aware of the focus size and the blast path of the machine they are operating.

Apart from this, lithotripter users would do well to take all measures to perform “good lithotripsy.” This means that they should take all measures to judiciously administer shock wave energy to avoid side effects and complications: precise imaging and targeting, optimal coupling, proper device settings, precise energy dose, voltage stepping, and proper release frequency. Proper adherence to these measures leads to improved outcome^2,3, reduced adverse effects^2–4 and improved cost-effectiveness.⁵

References

1. Krambeck AE, Gettman MT, Rohlinger AL, et al. Diabetes mellitus and hypertension associated with shock wave lithotripsy of renal and proximal stones at 19 years followup. J Urol 2006;175:1742–1747.

2. Chacko J, Moore M, Sankey N, et al. Does a slower treatment rate impact the efficacy of extracoporeal shock wave lithotripsy for solitary kidney or ureteral stones? J Urol 2006;175:1370–1374.

3. Pishchalnikov YA, McAteer JA, Williams JC Jr. Effect of firing rate on the performance of shock wave lithotriptors. BJU Int 2008;102:1681–1686.

4. Skolarikos A, Alivizatos G, de la Rosette J. Extracorporeal shock wave lithotripsy 25 years later: complications and their prevention. Eur Urol 2006;50:981–990.

5. Koo V, Beattie I, Young M. Improved cost-effectiveness and efficiency with a slower shockwave delivery rate. BJU Int 2010;105:692–696.

Geert G. Tailly, M.D.

A clinical nomogram to predict the successful shock wave lithotripsy of renal and ureteral calculi. Wiesenthal JD, Ghiculete D, Ray AA, Honey RJ, Pace KT, Division of Urology, Department of Surgery, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.

J Urol 2011;186:556–562.

Purpose: Although shock wave lithotripsy is dependent on patient and stone related factors, there are few reliable algorithms predictive of its success. In this study we develop a comprehensive nomogram to predict renal and ureteral stone shock wave lithotripsy outcomes.

Materials and Methods: During a 5-year period data from patients treated at our lithotripsy unit were reviewed. Analysis was restricted to patients with a solitary renal or ureteral calculus 20 mm or less. Demographic, stone, patient, treatment and 3-month followup data were collected from a prospective database. All patients were treated using the Philips Lithotron^® lithotripter.

Results: A total of 422 patients (69.7% male) were analyzed. Mean stone size was 52.3 ± 39.3 mm(2) for ureteral stones and 78.9 ± 77.3 mm(2) for renal stones, with 95 (43.6%) of the renal stones located in the lower pole. The single treatment success rates for ureteral and renal stones were 60.3% and 70.2%, respectively. On univariate analysis predictors of shock wave lithotripsy success, regardless of stone location, were age (p = 0.01), body mass index (p = 0.01), stone size (p < 0.01), mean stone density (p < 0.01) and skin to stone distance (p < 0.01). By multivariate logistic regression for renal calculi, age, stone area and skin to stone distance were significant predictors with an AUC of 0.75. For ureteral calculi predictive factors included body mass index and stone size (AUC 0.70).

Conclusions: Patient and stone parameters have been identified to create a nomogram that predicts shock wave lithotripsy outcomes using the Lithotron lithotripter, which can facilitate optimal treatment based decisions and provide patients with more accurate single treatment success rates for shock wave lithotripsy tailored to patient specific situations.

Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

DOI:10.1016/j.juro.2011.03.109

Commentary

This is probably one of the very best articles on shock wave lithotriopsy related subjects ever published. The study is carefully designed and meticulously executed. Above all, the discussion offers reasonable explanations for the observations made. As the authors judge success following one single treatment session, their definition of success both for renal and ureteral calculi in this setup is reasonable.

In renal stones, patient age, stone area and skin-to-stone distance (SSD) are found to be predictive variables for successful ESWL. Stone area seems to be a logical predictive variable. Patient age would seem to be less logical. However, the suggestion supported by a reference from the physics literature that differences in tissue elasticity with differences in shock wave transmission to the stone could be responsible for this sounds reasonable and acceptable.¹

In this series intrarenal stone location proved not to be a predictive variable. In the treatment of renal stones, SSD and not BMI proved predictive, whereas in the treatment of ureteral stones, BMI and not SSD was predictive. Although BMI and SSD would seem directly related, the authors attribute this difference to the difference in SW paths in the treatment of renal and ureteral stones and the fact that SSD for ureteral stones is significantly higher than for renal calculi, thus exceeding an SSD threshold beyond which the predictive value in a multivariate model is lost. Again, a reasonable explanation.

That success rates for ureteral stones are lower than for renal stones is an established observation. The authors attribute this to a combination of factors: a lack of urine surrounding the stone leading to less efficient comminution, a greater SSD and more difficult targeting in certain locations.

Despite the relatively high accuracy and reliability of the nomograms presented, the authors stress the importance of other less quantifiable variables in the administration of shock waves that may influence outcome: adequate stone targeting, expertise of the urologist operating the lithotripter, coupling efficiency, shock wave release frequency, etc. Apart from the variables presented in the nomograms, these elements of “good lithotripsy” can also influence outcome to an important extent.

It would indeed be very useful to further validate these nomograms for various types of lithotripters and in other centers. One welcomes the fact that steps in this direction have already been taken by the authors.

Reference

1. Ohl SW, Klaseboer E, Khoo BC. The dynamics of a non-equilibrium bubble near bio-materials. Phys Med Biol 2009;54:6313–6336.

Geert G. Tailly, M.D.

Introduction

The following selected articles provide insight into various issues that affect the treatment of symptomatic BPH, and focus on current popular electrosurgical and laser modalities, and related complications, such as bleeding and sexual dysfunction. Additionally, a novel, minimally invasive short procedure is introduced that has the appeal of being an office-base alternative that appears simple and facile to perform.

Alexis E. Te, M.D.

Bipolar plasma vaporization vs monopolar and bipolar TURP—A prospective, randomized, long-term comparison. Geavlete B, Georgescu D, Multescu R, Stanescu F, Jecu M, Geavlete P, “Saint John” Emergency Clinical Hospital, Department of Urology, Bucharest, Romania.

Urology 2011 Jul 27. [Epub ahead of print]

Objectives: To perform a prospective, randomized, long-term comparison between bipolar plasma vaporization of the prostate (BPVP), bipolar transurethral resection in saline (TURis), and monopolar transurethral resection of the prostate (TURP) concerning the perioperative and follow-up parameters.

Methods: A total of 510 patients with benign prostatic hyperplasia (BPH), Q_max < 10 mL/s, International Prostate Symptom Score (IPSS) >19, and prostate volume between 30 and 80 mL were enrolled in the trial. All cases were evaluated preoperatively and at 1, 3, 6, 12, and 18 months after surgery by IPSS, quality of life, Q_max, and ultrasonography.

Result: Each study arm including 170 cases emphasized similar preoperative parameters. The capsular perforation and intraoperative bleeding rates as well as the mean hemoglobin drop were significantly decreased for BPVP by comparison with TURis and TURP. The postoperative hematuria, blood transfusion, and clot retention rates were significantly higher in the TURP group. The operation time was significantly shorter only for BPVP patients, whereas the catheterization period and hospital stay were significantly reduced for BPVP, followed by TURis. The rates of irritative symptoms and urethral strictures were similar in the 3 series. The recatheterization, bladder neck sclerosis, and retreatment rates were significantly lower in the BPVP group. During the 1, 3, 6, 12, and 18 months' follow-up, the BPVP series emphasized significantly superior parameters in terms of IPSS and Q_max.

Conclusions: BPVP represents a valuable endoscopic treatment alternative for BPH patients, with superior efficacy and satisfactory complication rate. The long-term follow-up emphasized durable improvements of the postoperative parameters for BPVP.

Copyright © 2011 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.urology.2011.03.072

Commentary

This is an interesting prospective, randomized single center study that examines bipolar electrovaporization vs. bipolar TURP vs. standard monopolar TURP. It is important to note that bipolar technology essentially decreases the risk of dilutional hyponatremia if the irrgation fluid utilized is normal saline instead of nonionic hypotonic solution such as glycine irrigation. However, the study is focused on hemostasis effect of the technologies. It is already well known that large surface electrovaporization technology has the advantageous effect of hemostasis by providing a layer of coagulated tissue in the path of vaporization that basically seals off potential bleeding vessels. This effect has already been well demonstrated by older monopolar electrosurgical technology. Thus, it is not surprising to see less bleeding with bipolar electrovaporization techniques vs. resection techniques, both bipolar and monopolar. Additionally, while the focus is always on the technology, the reader should keep in mind that the technology is dependent on the mechanical technique of the committed surgeon performing the procedure. Thus, with a loop resection technique, it is not surprising that perforation and bleeding is higher since an experienced pinpoint coagulation skill is more important with resection technique than a roller/sliding contact vaporization technique. Additionally, it is observed that operative, catheterization and hospital times are all less for vaporization. However, these may be easily attributed to the effect of better hemostasis with vaporization technique which can easily results in improvements in all these parameters.

Alexis E. Te, M.D.

Outcomes and complications after 532 nm laser prostatectomy in anticoagulated patients with benign prostatic hyperplasia. Chung DE, Wysock JS, Lee RK, Melamed SR, Kaplan SA, Te AE, Section of Urology, University of Chicago and Department of Surgery, Mount Sinai Hospital, Chicago, IL.

J Urol 2011;186:977–981.

Purpose: Patients on anticoagulation are at high risk for bleeding after electrocautery transurethral resection of the prostate or open prostatectomy and they are often denied surgery for symptomatic benign prostatic hyperplasia. Using photoselective vaporization of the prostate, patients at high risk may safely undergo surgery. We explored outcomes and complications after photoselective vaporization of the prostate in an anticoagulated, high risk cohort.

Materials and Methods: Between 2002 and 2008, 162 men on systemic anticoagulation underwent photoselective vaporization of the prostate. Data were collected on demographics, comorbidities, complications, serum sodium, hematocrit, maximum flow rate, post-void residual urine, International Prostate Symptom Score and complications.

Results: Mean ± SD age was 72 ± 8 years, mean baseline prostate volume was 91 ± 49 gm and mean prostate specific antigen was 4.1 ± 5 ng/ml. Of the patients 31 (19%) were on warfarin, 101 (62%) were on acetylsalicylic acid, 19 (12%) were on clopidogrel and 11 (7%) were on 2 or more anticoagulants. Median American Society of Anesthesiologists class was 3 and mean Charlson comorbidity index was 5. Median operative time was 105 minutes and mean energy use was 280 ± 168 kJ. The immediate mean hematocrit decrease was 1.94% ± 2.42%. One patient who received excessive intravenous fluids experienced heart failure. Complications within 30 days included urinary tract infection in 4 patients (2.5%) and delayed bleeding in 6 (4%). Three of these patients (50%) required blood transfusion and 1 (17%) required reoperation. In 2 years of followup 3 patients (2%) required repeat photoselective vaporization of the prostate. No incontinence or urethral stricture developed. Significant improvements occurred in International Prostate Symptom Score, maximum flow rate and post-void residual urine.

Conclusions: Results support using 532 nm photoselective vaporization of the prostate in patients at high risk on systemic anticoagulation, even those on 2 or more anticoagulation agents and with a large prostate requiring longer operative time. Few complications developed and significant durable clinical improvement was seen.

Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

DOI: 10.1016/j.juro.2011.04.068

Commentary

One of the highest risk populations to surgically treat for symptomatic BPH are patients with anticoagulation requirements due to coexisting medical morbidities such as those at increased risk for cerebrovascular events, thromboemobolic events, and cardiovascular ischemic events, as well as cardiopulmonary events. Often, in addition to the increased risk of bleeding is the added risk of limited tolerance to cardiovascular hemodynamic instability, creating challenging fluid management issues in these patients. As a result, offering treatment for essentially a quality of life improvement is a careful consideration of risk and benefit, and each case should be approached with caution. This report demonstrates the challenges of operating on actively anticoagulated patients, and demonstrates that if carefully selected, is a viable option with this technology. Of interest is that the technology can easily manage intraoperative bleeding issues, and the greatest challenges are those encountered postoperatively, where bleeding can easily recur even when anticoagulation status is carefully monitored. Thus, while there is a strong socioeconomic push for these high risk patients to be discharged home the same day after surgery, it is prudent to observe them postoperatively overnight prior to discharge.

Alexis E. Te, M.D.

TURP and sex: patient and partner prospective 12 years follow-up study. Mishriki SF, Grimsley SJ, Lam T, Nabi G, Cohen NP, Urology Department, Aberdeen Royal Infirmary, Grampian NHS Trust, Aberdeen, ^*Academic Clinical Practice, Department of Urology, Ninewells Hospital and Medical School, Dundee, UK.

BJU Int. 2011 Jun 28. [Epub ahead of print]

Study Type: Symptom prevalence (prospective cohort)

Level of Evidence: 1b

What's known on the subject? and What does the study add? Evidence that transurethral resection of the prostate (TURP) leads to erectile dysfunction (ED) is conflicting. Several studies claimed significant risk of ED after TURP for benign prostatic hyperplasia with some reporting complete loss of erection. Several studies have been retrospective or have not considered levels of pre-operative ED. ED associated with lower urinary tract symptoms frequently precedes TURP. TURP did not adversely affect erectile function. Pre-operative ED can be improved by TURP and long-term erectile function is maintained following TURP. The improvement was corroborated by the partners in the short, medium and long-term and was statistically significant.

Objective:

• To evaluate the effect of transurethral resection of the prostate (TURP) on sexual function in the short (6 months), medium (6 years) and long (12 years) term and assess the conformity between patient and partner regarding sexual function.

Patients and Methods:

• A prospective cohort study set at the Aberdeen Royal Infirmary University Hospital.

Results:

• In all, 120 (43%) men were sexually active preoperatively. At 6 months, 73 (61%) of these 120 men completed the SQ and all were sexually active.

Conclusions:

• Erectile dysfunction associated with LUTS frequently precedes TURP.

© 2011 The Authors. BJU International © 2011 BJU International.

DOI: 10.1111/j.1464-410X.2011.10396.x

Commentary

The issue of erectile dysfunction as an associated risk of TURP is traditionally well known. However, the method of assessment has always been questioned due to the lack of validated methods of assessment and reporting preoperatively and postoperatively. This is a well documented study that utilizes validated instruments of assessment to address this question, and it demonstrates that TURP generally should not adversely affect erectile function. Traditionally, in many treatment studies, erectile or sexual dysfunction is often reported as an adverse event. In light of the findings of this study, it is highly probable that many of these studies that report sexual dysfunction as an adverse event are not accurate and need to be analyzed in a fashion similar to this study.

Alexis E. Te, M.D.

Safety and feasibility of the prostatic urethral lift: a novel, minimally invasive treatment for lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). Woo HH, Chin PT, McNicholas TA, Gill HS, Plante MK, Bruskewitz RC, Roehrborn CG, Departments of Urology, University of Sydney, Sydney, NSW, Australia.

BJU Int 2011;108:82–88.

Objectives:

• To investigate the Prostatic Urethral Lift (PUL) procedure, a novel, minimally invasive treatment for symptomatic benign prostatic hyperplasia (BPH), which aims to mechanically open the prostatic urethra without ablation or resection.

Patients and Methods:

• The PULprocedure was performed on 19 men in Australia.

Results:

• All cases were successfully completed with no serious or unexpected adverse events (AEs).

Conclusions:

• We demonstrated in this initial experience that the PUL procedure is safe and feasible.

© 2011 The Authors. BJU International © 2011 BJU International.

DOI: 10.1111/j.1464-410X.2011.10342.x

Commentary

Most recent minimally invasive therapies focus on an ablative or thermotherapy mechanism of action to effectively improve lower urinary tract obstruction by relieving or decreasing bladder outlet obstruction due to prostatic tissue. This is a novel procedure that in essence seeks to “tack open” the prostatic urethra in order to open the prostatic channel effecting the obstruction. Simple in concept, and theoretically promising, the procedure will need to be vetted in multicenter, prospective randomized studies to determine its efficacy and simplicity in the hands of many. Further studies will determine if this simple procedure will be a viable option in the armamentarium of the office urologist.

Alexis E. Te, M.D.

Commentary

Animal models can provide useful information regarding pathophysiology of disease processes. This mouse knockout model of the sodium phosphate transporter, Npt2a, produced apatite deposits within the collecting ducts of these animals. While this is different from the Randall's plaque histology seen in idiopathic calcium oxalate stone formers, it is similar to some of the findings seen in humans harboring brushite stones.¹ Further investigations into why crystal deposition is less intense in older animals is certainly warranted and may eventuate in the development of strategies to facilitate intratubular crystal purging.

Reference

1. Evan AP, Lingeman JE, Coe FL, et al. Crystal-associated nephropathy in patients with brushite nephrolithiasis. Kidney Int 2005;67:576–591.

Dean G. Assimos, M.D.

Impact of dietary calcium and oxalate, and Oxalobacter formigenes colonization on urinary oxalate excretion. Jiang J, Knight J, Easter LH, Neiberg R, Holmes RP, Assimos DG, Department of Microbiology and Biotechnology, Northeast Agricultural University (JJ), Harbin, People's Republic of China.

J Urol 2011;186:135–139.

Purpose: Enteric colonization with Oxalobacter formigenes, a bacterium whose main energy source is oxalate, has been demonstrated to decrease the risk of recurrent calcium oxalate kidney stone formation. We assessed the impact of diets controlled in calcium and oxalate contents on urinary and fecal analytes in healthy subjects who were naturally colonized with O. formigenes or not colonized with O. formigenes.

Materials and Methods: A total of 11 O. formigenes colonized and 11 noncolonized subjects were administered diets controlled in calcium and oxalate contents. We assayed 24-hour urine collections and stool samples obtained on the last 4 days of each 1-week diet for stone risk parameters and O. formigenes levels. Mixed model analysis was used to determine the effects of colonization status on these variables.

Results:Urinary calcium and oxalate excretion were significantly altered by the dietary changes in O. formigenes colonized and noncolonized individuals. Mixed model analysis showed significant interaction between colonization status and oxalate excretion on a low calcium (400 mg daily)/moderate oxalate (250 mg daily) diet (p = 0.026). Urinary oxalate excretion was 19.5% lower in O. formigenes colonized subjects than in noncolonized subjects on the low calcium/moderate oxalate diet (mean ± SE 34.9 ± 2.6 vs 43.6 ± 2.6 mg, p = 0.031).

Conclusions: Results suggest that O. formigenes colonization decreases oxalate excretion during periods of low calcium and moderate oxalate intake.

Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

DOI: 10.1016/j.juro.2011.03.006

Commentary

Enteric colonization with the anaerobic bacterium O. formigenes has been demonstrated to reduce the risk of recurrent calcium oxalate kidney stone formation. These experiments demonstrate that this may protective during periods of low calcium and moderate oxalate intake. Further studies are needed to determine if colonization is protective during more robust oxalate intake and low calcium consumption. Perhaps colonization or re-colonization may prove to be a useful strategy to prevent recurrent calcium oxalate kidney stone formation.

Dean G. Assimos, M.D.

Commentary

The shortcomings of white light cystoscopy in differentiating non-papillary urothelial carcinoma from inflammatory lesions and delineation of tumor boundaries has been well described and discussed. Several newer optical imaging technologies have been recently approved for use in the urinary tract, including fluorescence cystoscopy, narrow band imaging, and optical coherence tomography. All of these technologies are attempting to provide adjuvant information beyond white light cystoscopy to improve the accuracy of diagnosis and treatment of urothelial carcinoma.

Another emerging technology under investigation is probe-based confocal laser endomicroscopy (pCLE). The authors of this study investigate real-time imaging with pCLE to provide an atlas and further information to facilitate treatment of urothelial carcinoma. The technology has already been approved for clinical use in the respiratory and gastrointestinal tracts, and it has shown excellent results in discovering Barrett's esophagus. The hope is that the same accuracy could be developed for determining carcinoma in situ or upper tract urothelial carcinoma (in which biopsies through a ureteroscope can be challenging) in real time imaging in urology.

In order to obtain imaging, all patients need to receive intravenous or intravesical fluorescein for staining of the urothelial cells. Fluorescein only stains extracellularly and, therefore, nuclear morphology review is not possible as it is in H&E staining. Other restrictions of this technology include the depth of penetration, which is limited to the lamina propria in intact mucosa, and a small field of view, which confines the area of surveyed mucosa. In fact, it took on average 15.5 minutes to get limited images in these study participants and it is impractical to scan the entire bladder. However, the authors have improved on decreasing the probe size from 2.6 mm to 1.4 mm in size. The 1.4 mm probe provides 3.5 μm of resolution and a field of view of 600 μm. The smaller probe can be used through a flexible cystoscope. Using an image analysis computer algorithm called mosaicing, pCLE technology has also been significantly improved in that it can provide a composite image and increased field of view. This allows the investigator to visualize tissue of interest in the context of the surrounding cell layers/glands.

Throughout the article, the authors provide excellent images of the pCLE technology in comparison to the gross appearance and H&E staining. In my opinion, it is one of the first micron-scale resolution technologies that may be developed into images that can be interpreted by most urologists and be useful as an adjunctive imaging modality for bladder cancer. Current prospective diagnostic accuracy studies are underway to assess the sensitivity and specificity of these confocal criteria in the diagnosis of bladder cancer.

David A. Duchene, M.D.

Stimulation of soluble guanylate cyclase improves renal recovery after relief of unilateral ureteral obstruction. Wang-Rosenke Y, Mika A, Khadzhynov D, Loof T, Neumayer HH, Peters H, Department of Nephrology and Center for Cardiovascular Research, Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany.

J Urol 2011;186:1142–1149.

Purpose: The antifibrotic effects of soluble guanylate cyclase stimulation and cyclic guanosine monophosphate production have been observed in cases of anti-thy1-induced renal disease. We analyzed the action of the specific soluble guanylate cyclase stimulator BAY 41-8543 on the renal recovery phase in rats with unilateral ureteral obstruction after obstruction was relieved.

Materials and Methods: Sprague-Dawley^® rats underwent reversible unilateral ureteral obstruction for 5 days, after which obstruction was relieved. Rats were randomly assigned to unilateral ureteral obstruction and unilateral ureteral obstruction plus BAY 41-8543 (10 mg/kg body weight daily). Seven days after relief of obstruction we determined treatment effects on renal atrophy, apoptosis, fibrosis and nitric oxide/cyclic guanosine monophosphate signaling.

Rresults: Untreated obstructed rats showed mildly increased systolic blood pressure, marked tubular atrophy and apoptosis, tubulointerstitial macrophage infiltration and fibrosis. Plasma cyclic guanosine monophosphate levels were unaltered in untreated rats with obstruction while renal soluble guanylate cyclase mRNA expression was increased. BAY 41-8543 administration significantly increased plasma cyclic guanosine monophosphate, which was paralleled by significant decreases in systolic blood pressure, renal tubular diameter, apoptosis and renal macrophage infiltration. Also, soluble guanylate cyclase stimulation decreased tubulointerstitial fibrosis, as shown by tubulointerstitial volume, matrix protein accumulation, α-smooth muscle actin expression, collagen IV deposition and transforming growth factor-β1 mRNA expression.

Conclusions: Soluble guanylate cyclase stimulation by BAY 41-8543 increases cyclic guanosine monophosphate production and subsequently enhances renal recovery after unilateral ureteral obstruction relief through an array of pathways. This finding suggests that soluble guanylate cyclase stimulation may serve as a novel treatment approach to restore or preserve renal structure and function in cases of obstructive kidney disease.

Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

DOI: 10.1016/j.juro.2011.04.108

Commentary

Obstructive nephropathy is a leading cause of chronic kidney disease in children worldwide and also contributes to progressive renal failure in adults. Even though children with posterior urethral valves, children and adults with ureteropelvic junction obstruction, individuals with repeated temporarily obstructing stones, and men with chronic outlet obstruction can have the urinary obstruction effectively resolved by means of surgical correction, many of these renal units will still progress to end-stage renal disease. A complex cascade of events is thought to occur to cause the progressive renal disease which culminates in tubular atrophy, tubulointerstitial inflammation and fibrosis. Efforts are ongoing to develop compounds to prevent the progression to renal fibrosis in these disease states.

The authors of this manuscript study the antifibrotic effects of soluble guanlyate cyclase stimulation and cyclic guanosine monophosphate production in the nitric oxide pathway to prevent fibrotic kidney disease. Deficient nitric oxide production and nitric oxide signaling have been identified as key pathways in many experimental and human renal diseases. This study specifically analyzed the soluble guanylate cyclase stimulator BAY 41-8543 in the renal recovery phase in rats with unilateral ureteral obstruction after the obstruction was relieved. The soluble guanylate cyclase/cGMP pathway is one of multiple downstream signaling pathways in the nitric oxide cycle and is a new target for therapeutic intervention for nitric oxide deficient states (both acute and chronic) in renal disease.

Seven days after relief of unilateral obstruction, BAY 41-8543 rats showed significantly increased plasma cyclic guanosine monophosphate, which was paralleled by significant decreases in systolic blood pressure, renal tubular diameter, apoptosis and renal macrophage infiltration. The soluble guanylate cyclase stimulation also decreased tubulointerstitial fibrosis as shown by tubulointerstitial volume, matrix protein accumulation, α-smooth muscle actin expression, collagen IV deposition and transforming growth factor-β1 mRNA expression.

Overall, soluble guanylate cyclase stimulation by BAY 41-8543 enhanced renal recovery after unilateral ureteral obstruction relief through an array of pathways in the rat model. BAY 41-8543 was delivered by oral administration in this study and appeared to have minimal adverse effects. This compound is currently undergoing clinical phase 1 and phase 2 trials in humans. The newly developed pharmacological stimulator of soluble guanylate cyclase will hopefully be available in the future to preserve renal recovery in the setting of both transient and chronic ureteral obstructive conditions.

David A. Duchene, M.D.

Commentary

This is an informative retrospective review of the incidence of perioperative complications after robotic assisted partial nephrectomy (RAPN) in four academic institutions of excellence. All surgeons from the participating institutions had considerable experience with laparoscopic partial nephrectomy before embarking on use of the robotic interface. Robotic interface definitively provides superior optical magnification, three-dimensional vision and facilitates suturing. The take-home message from this article is that even in the hands of an expert surgeon with substantial prior laparoscopic experience, using an experienced surgeon assistant and nursing team in robotics at an academic center, the complication rates are 15.8%, though long-term renal function and oncologic outcomes are not reported. It is interesting to note that nephrectomy was performed in seven patients, in one case due to bleeding and in six cases due to positive margin. Similarly, in a study of 62 cases from Europe, the complication rate was 16.1%, median hospital stay was 5 days, and a statistically significant postoperative rise in creatinine over baseline at 3 month follow-up was noted.¹

In evaluating our own series of 175 partial nephrectomies, using a surgeon controlled bulldog vascular clamp and the 4-arm daVinci Si unit so as to have maximum independence for the surgeon, we still experienced a complication rate of over 10% (unpublished data).

RAPN is an attractive alternative to open partial nephrectomy but a challenging one for selected small renal masses. Prospective randomized trials are needed.

Reference

1. Mottrie A, De Naeyer G, Schatteman P, et al. Impact of the learning curve on perioperative outcomes in patients who underwent robotic partial nephrectomy for parenchymal renal tumours. Eur Urol 2010;5:127–132.

Ashok K. Hemal, M.D.

Near infrared fluorescence imaging with robotic assisted laparoscopic partial nephrectomy: initial clinical experience for renal cortical tumors. Tobis S, Knopf J, Silvers C, Yao J, Rashid H, Wu G, Golijanin D, Departments of Urology and Pathology, University of Rochester Medical Center, Rochester, NY.

J Urol 2011;186:47–52.

Purpose: We evaluated the utility of near infrared fluorescence of intravenously injected indocyanine green in performing robotic assisted laparoscopic partial nephrectomy. In addition, we evaluated the initial performance of a novel near infrared fluorescence imaging system integrated into the da Vinci^® Si Surgical System during robotic assisted laparoscopic nephrectomy.

Materials and Methods: Fluorescence imaging for the da Vinci Si Surgical System was used for all cases. Indocyanine green was injected before near infrared imaging. Immediate imaging assessed the renal vasculature while delayed imaging differentiated renal cortical tumors from normal parenchyma. The intraoperative performance of near infrared fluorescence of intravenous indocyanine green was evaluated for tumor appearance relative to surrounding renal parenchyma as well as identification of the renal vasculature.

Results: A total of 11 patients underwent robotic assisted laparoscopic nephrectomy with 2 converted to robotic assisted laparoscopic radical nephrectomy. Indocyanine green injections were repeated up to a total of 5 times depending on the goal of visualization. Of the 11 patients 10 demonstrated malignancy on final pathology. Of the malignant tumors 7 were hypofluorescent and 3 were isofluorescent compared to the surrounding renal parenchyma. Near infrared fluorescence imaging delineated the vascular anatomy in all cases. All surgical margins were negative on final pathology.

Conclusions: Intraoperative imaging of indocyanine green with near infrared fluorescence is a safe and effective method to accurately identify the renal vasculature and to differentiate renal tumors from surrounding normal parenchyma. The capacity for multimodal imaging within the surgical console further facilitates this imaging. Further study is needed to determine if this technique will help improve outcomes of robotic assisted laparoscopic nephrectomy.

Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

DOI: 10.1016/j.juro.2011.02.2701

Commentary

This article reports the evaluation of a novel method of intraoperative visualization of renal cortical tumor margins and renal vasculature during robot assisted laparoscopic partial nephrectomy (RALPN). The currently available technology for viewing near infrared fluorescence (NIRF) images during RALPN requires a separate scope and viewing system. A modification of the da Vinci Si Surgical System is required in its light source, along with several other changes. In this series, 11 patients underwent RALPN, in which two converted to radical nephrectomy. NIRF imaging delineated the vascular anatomy in all cases. All surgical margins were negative on final pathology. The median minimum distance between the tumor and resection margin was 1 mm. The median number of ICG injections was three (range, 1–5). The current cost of indocyanine green (ICG) is $85 per patient, in addition to the charges for modification of the robotic system.

At Wake Forest University we carried out a study in 31 patients to evaluate the utility of NIRF with intravenously injected ICG for robotic partial nephrectomy. We only used a single dose of 2 mL ICG injection for NIRF imaging. This technique helped in only two steps of the procedure—identifying renal vessels initially, and in an attempt to maintain normal renal parenchyma all around the tumor in order to decrease positive margins (unpublished data).

In summary, NIRF is safe and aids in identification of the renal vasculature, but only for an initial period. Subsequently, all vasculature looks green and it becomes difficult to differentiate tumors from the surrounding renal parenchyma. Multicenter trials and comparative study are required to prove its real benefit.

Ashok K. Hemal, M.D.

Commentary

The use of microwave ablation (MWA) therapy for renal tumors remains of great interest. It has been successfully used during liver ablation and has theoretical advantages, such as the ability to achieve higher treatment temperature, improved temperature homogeneity within the tumor, and absence of an electrical current that could cause complications such as grounding pad burns. Castle and colleagues present here their clinical experience in treating 10 patients with a single, solid enhancing renal tumor over the course of 5 months. These patients underwent either laparoscopic or computed tomography-guided percutaneous MWA with a Valleylab generator (Covidien, Valleylab, Boulder, CO) at a power of 45 watts. Patients were followed up with contrast-enhanced computed tomography at 1 month, 6 to 12 months, and annually thereafter. Tumor sizes averaged 3.65 cm (range 2.0–5.5 cm). The authors established a treatment endpoint of >60° C as determined by nonconducting peripheral fiberoptic thermometers. The tumors were quite variable in their positions and depth, being located in the upper, mid, and lower aspects of the kidney and including 5 endophytic tumors that extended to the collecting system.

Of greatest interest to our readership, I believe, is the result of this study. The recurrence rate, as defined by persistent enhancement and with tissue confirmation in all cases, was 38% (3 of 8 patients with available follow-up). Of additional interest is that the intraoperative and postoperative complication rates were 20% and 40%, which resulted in the authors' concluding that this treatment is associated with a poor oncologic outcome and a significant complication rate. The authors continue to believe that MWA still has some promising theoretical advantages and should not be discarded on the basis of this report but that additional studies should be considered.

The strengths of this current study include the fact that every patient was followed for a minimum of 14 months, for an average follow-up of 17.9 months. The treatment was monitored using simultaneous fiberoptic thermometry during ablative therapy, for which these investigators have advocated. Additionally, this study represents approximately 30% of the reported clinical experience with MWA, with a total of 32 patients thus reported, including this study. The authors present a succinct, informative review of the prior studies.

The significant drawbacks of MWA, at least with the technology used in this study, are the following: the probes are relatively large (13 gauge) compared to the probes used for radiofrequency ablation or cryoblation. Additionally, all of the treatment protocols are based on liver experience, which has much more homogeneity and is a larger volume organ than the kidney. The latter may explain some of the very significant complications reported by the authors, which included complete necrosis of the ureteropelvic junction as well as melting of a thermometer plastic sheath resulting in a retained foreign body and requiring delayed nephrectomy. Other major complications included development of a urinoma requiring surgical intervention. Four of the 10 patients had complications.

The data reported by the study are very important, and the authors should be congratulated for presenting this data in such an objective and straightforward manner. Despite being performed by a team highly experienced with a variety of ablative therapies and with simultaneous temperature monitoring, inadequate oncologic control was obtained at a very high cost of complications and renal loss. It is thus appropriate that the authors conclude that the standards of meeting oncologic control, adequate morbidity, and renal preservation comparable to nephron-sparing standards have not been met by MWA. It seems wise at this point to consider that the current approved standards for liver MWA should not be automatically applied in the clinical evaluation of renal MWA and that more basic preclinical or phase I groundwork be performed prior to proceeding with additional clinical experience. In the meantime, we all will continue to search for the perfect ablative option.

Surena F. Matin, M.D.

Cost-effectiveness analysis of nephron sparing options for the management of small renal masses. Chang SL, Cipriano LE, Harshman LC, Garber AM, Chung BI, Division of Urology, and Center for Surgery and Public Health, Brigham and Women's Hospital, Boston, MA.

J Urol 2011;185:1591–1597.

Purpose: A recent increase in the detection of contrast enhancing renal masses 4 cm or smaller suspicious for malignancy has led to the widespread use of nephron sparing options. Limited data exist to help clinicians decide which of these competing nephron sparing therapies is most appropriate. We performed a cost-effectiveness analysis to evaluate the relative clinical and economic merits of commonly available nephron sparing strategies for small renal masses.

Materials and Methods: We developed a decision analytic Markov model estimating the costs and health outcomes of treating a healthy 65-year-old patient with an asymptomatic unilateral small renal mass using competing nephron sparing options of immediate intervention (ie open and laparoscopic partial nephrectomy as well as laparoscopic and percutaneous ablation), active surveillance with possible delayed intervention and nonsurgical management with observation. Benefits were measured in quality adjusted life-years. We used a societal perspective, lifetime horizon and willingness to pay threshold of $50,000 per quality adjusted life-year gained. Model results were assessed with sensitivity analyses.

Results: In the base case scenario the least costly option was observation and the optimal option was immediate laparoscopic partial nephrectomy, which had an incremental cost-effectiveness ratio of $36,645 per quality adjusted life-year gained compared to surveillance with possible delayed percutaneous ablation. Results were sensitive to age at diagnosis, health status and tumor size.

Conclusions: Immediate laparoscopic partial nephrectomy is the preferred nephron sparing option for healthy patients younger than 74 years old with a small renal mass. Surveillance with possible delayed percutaneous ablation is a cost-effective alternative for patients with advanced age or significant comorbidities. Observation maximizes quality adjusted life-years in patients who are poor surgical candidates or with limited life expectancy (less than 3 years).

Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

DOI: 10.1016/j.juro.2010.12.100

Commentary

Multiple clinical studies exist comparing the results of the different options for the management of small renal masses. This study by Chang and colleagues is unique, and their thoughtful and methodical approach to evaluating nephron-sparing options for the management of the small renal mass is very important. The authors performed a cost-effectiveness analysis using a decision analytic Markov module, which estimated the costs and health outcomes of treating an index case of a healthy 65-year-old patient with an asymptomatic unilateral small renal mass. The authors looked at the options of immediate intervention with open or laparoscopic partial nephrectomy, laparoscopic and percutaneous ablation, active surveillance with possible delayed intervention, or complete nonsurgical management. The authors looked at a multitude of associated factors that could affect the cost-effectiveness of these procedures, including rates of new onset postoperative chronic kidney disease (CKD), the detection of residual or recurrent tumors necessitating secondary and tertiary procedures, development of metastatic disease requiring first or second line systemic therapies, and disease progression requiring supportive care and an assumed 1 week of hospice care. The authors additionally inputted baseline age-specific quality of life (QOL) estimates from a population survey available in the literature, and they were able to account for QOL reduction with each surgical intervention, which is assumed to have resolved by 3 months. They also included the indirect cost of recovery based on reimbursement of home health care services, which probably underestimates such costs but was a valiant effort at trying to quantitate a traditionally uncaptured data point.

I found this study to be highly informative and potentially transformative in that it introduces a new paradigm for an era of personalized treatment that is based on clinical efficacy as well as cost effectiveness. The authors found that in the index case scenario, the least costly option was observation, but the optimal option was immediate laparoscopic partial nephrectomy, which had an incremental cost-effectiveness ratio of $36,645 per quality-adjusted life year gained. The next most optimal option was surveillance followed by percutaneous ablation.

Of additional great interest to our readership may be that the single least cost-effective therapy was immediate laparoscopic ablation. In no scenario was this approach cost-effective. The authors did find the results were sensitive to the patient's age at diagnosis, the health status of the patient, and tumor size. The authors' evaluation of alternative scenarios showed that surveillance with possible delayed percutaneous ablation was a cost-effective alternative for older and sicker patients, and observation maximized quality-adjusted life years in patients with less than a 3-year life expectancy.

An additional important take-home message from this study is that extirpative options have significant cost savings compared with ablative therapies because of the ability to confirm pathologically the presence of benign tumors, which would save substantial follow-up costs as well as patient anxiety. This advantage is magnified in younger patients as the cost of postoperative surveillance becomes additive over time. This study adds cost-effectiveness data to existing clinical data that histologic proof of disease remains paramount in the management of the small renal mass and renal cell carcinoma.

The advantages of this study thus include the inclusion of indirect costs, the cost savings of identifying benign tumors, and the cost of secondary and tertiary local and systemic therapies. This study does have several significant limitations despite the use of powerful cost-effectiveness software. Certain assumptions had to be made by the authors so they could perform the analysis. These assumptions include an incidence of 25% of benign small renal masses, exclusion of a diagnostic percutaneous biopsy (which should always be included in the clinical pathway of ablative therapies and arguably with surveillance also), a willingness to pay $50,000 per quality-adjusted life year gained, a limit of 4 cm for performing radical nephrectomy vs. surveillance or nephron-sparing options, an assumption of unique rates of new onset CKD for each intervention (which was not specified), and estimation that nearly 90% of patients whose disease was managed with delayed option strategy ultimately underwent intervention. Also, the dataset did not take into account robotic partial nephrectomy. Therefore the reader has to be careful in translating some of the results as some of these assumptions may not always be relevant to every practice. For example, the authors' describing that the above assumptions translated into a 7.25% increase in the number of patients with metastatic disease as a result of being placed on surveillance is not supported by the current literature. An additional finding not completely supported by the current literature is that their model estimated recurrent or residual disease after ablation in 20% of patients. This is nearly twice the rate as reported by the meta-analysis performed by the American Urologic Association, but it is possible that as longer follow-up data mature, this prediction will ring true.

The data presented in the study are very important for our readership and particularly for those who are actively engaged in the practice of ablative therapies. With the increasing attention to cost-effective therapies, the urologists' fiscal responsibility for the health care dollar will be challenging in the context of exploring new technologies. It is no small matter that, in 2009, more than $4.4 billion dollars was spent on treating renal tumors, and all of our daily individual clinical decisions add to this cost. It is thus humbling to see that laparoscopic ablation was not preferred in any scenario modeled by the authors. Does this spell the end of laparoscopic ablation? Probably not as there is always challenging patient and tumor anatomy, but what is clear is that where the technology exists to perform the procedure percutaneously, this should be considered. There are those who argue that percutaneous therapies have lower efficacy, but it has been my belief that it is not the approach that is associated with efficacy but the user of the technology, who is in turn is shaped by his or her clinical background and experience.

While some readers may not be fully aware of some of the population-based terms, I strongly recommend reading this article if you are in any way involved in the treatment of small renal masses. Additionally, I believe this study can be used as supportive material when advocating for payment by insurance companies for those patients undergoing ablative therapies, particularly if after a period of surveillance.

Surena F. Matin, M.D.