Commentary

This retrospective, multi-institutional study evaluates the long-term oncologic outcomes of 73 patients who underwent laparoscopic radical nephrectomy (LRP) for pathologically confirmed renal cell carcinoma. This study is not a prospective comparative evaluation but it does provide important results that can be compared to the literature on open radical nephrectomy. The number seems small but acquiring meaningful data in 73 patients over 10 or more years is not an easy task.

As would be expected, higher grade and stage disease results in a lower cancer-specific and recurrence-free survival. These results are very comparable to the open surgical data. The authors note that there is no correlation between complication, recurrence or survival rates whether the operation was approached by the transperitoneal or retroperitoneal route. There were no local or port site recurrences, which was an early concern with the implementation of laparoscopic kidney cancer surgery in the 1990s.

Laparoscopic radical nephrectomy has become the standard of care for the vast majority of renal cell carcinomas that are not candidates for a partial nephrectomy or thermal ablative technique. Exceptions would be renal tumors that demonstrate extensive regional spread or caval involvement. Such cases should be approached with open surgery for the vast majority of urologic surgeons. A previously published study shows that LRP is taught in most U.S. and Canadian residency surgical programs and is viewed as the gold standard.¹ The last 20 years have seen an amazing shift in surgical approaches to renal masses of which the patients are the beneficiaries.

Reference

1. Duchene DA, Moinzadeh A, Gill IS, Clayman RV, Winfield HN. Survey of residency training in laparoscopic and robotic surgery. J Urol 2006;176:2158–2166.

Howard N. Winfield, M.D.

Nephron-sparing surgery is equally effective to radical nephrectomy for T1BN0M0 renal cell carcinoma: a population-based assessment. Crépel M, Jeldres C, Perrotte P, Capitanio U, Isbarn H, Shariat SF, Liberman D, Sun M, Lughezzani G, Arjane P, Widmer H, Graefen M, Montorsi F, Patard JJ, Karakiewicz PI, Cancer Prognostics and Health Outcomes Unit, University of Montreal, Montreal, Quebec, Canada; Rennes University Hospital, Rennes, France.

Urology 2010;75:271–275.

Objectives: To test the effect of nephron-sparing surgery (NSS) vs radical nephrectomy (RN) on cancer-specific mortality (CSM) in patients with T1bN0M0 renal cell carcinoma (RCC) in a population-based cohort. To date, only few series from tertiary care centers supported the use of NSS for T1bN0M0 (range 4–7 cm) RCC.

Methods: The Surveillance, Epidemiology, and End Results database allowed us to identify 275 NSS (5.3%) and 4866 RN (94.7%) patients treated for T1bN0M0 RCC between 1988 and 2004. Analyses matched for age, year of surgery, tumor size, and Fuhrman grade addressed the effect of nephrectomy type (NSS vs RN) on CSM.

Results: Five years after surgery, the surviving proportions of NSS and RN patients matched for age, tumor size, and year of surgery were respectively 91.4 and 95.3% and 90.1 and 93.8% in the cohort, where additional matching for Fuhrman grade was performed. Neither of the matched analyses resulted in statistically significant CSM difference (P = .1 and .4) between NSS and RN. Similarly, competing-risks regression analyses based on both matching schemes also failed to reveal statistically significant CSM differences (P = .3 and .3).

Conclusions: Our study represents the largest and the only population-based analysis of cancer control efficacy of NSS vs RN in T1bN0M0 RCC. It indicates that NSS does provide equivalent cancer control relative to RN. In consequence, based on cancer control equivalence, NSS should be given equal consideration to RN in patients with T1bN0M0 lesions.

DOI: 10.1016/j.urology.2009.04.098

Commentary

Masses suspected of harboring renal cell carcinoma are best treated by surgical excision. Assuming the tumor location is reasonable and the patient's health is adequate, lesions 4 cm or less (T1A) should preferentially be treated by partial nephrectomy. Numerous studies over the past decade have supported this view in terms of oncologic safety, along with optimal preservation of renal function, thus minimizing long-term problems of renal insufficiency and cardiovascular events.

This study examines the SEER database for renal cell carcinoma tumors 4–7 cm (T1bNOMO) between 1988 and 2004. The study group includes 275 patients undergoing nephron-sparing surgery (5.3%) compared to 4,866 carefully matched patients undergoing radical nephrectomy (94.7%). Two types of statistical analyses were used.

The authors found no statistical difference in cancer-specific mortality between the two groups with a median follow-up of 30–33 months. Strong points of this study are the use of the SEER database, which is probably more reflective of the “everyday urology practices” in North America rather than results of many previous studies coming from academic centers of excellence for renal surgery. However, I was concerned by not clearly knowing the location of the T1b tumors in each group. For example, did some patients undergo a radical nephrectomy for a 5 cm tumor because it was totally endophytic and perhaps close to renal hilum, as opposed to a 5 cm tumor hanging off the lower pole of the kidney—one obviously more conducive to a partial nephrectomy? This important data is not included. In addition, as the authors point out in their discussion, “because of the relative underuse of NSS in the United States, its indications in the SEER database may have been absolute for most T1bNOMO cases.”

The bottom line is that urologists should keep their minds open for consideration of nephron-sparing surgery in masses 7 cm or less. However, sound judgment should reflect the safety of this type of surgery in their hands or in those of other perhaps more skilled surgeons. The primary objective is to cure the patient. If this cannot be safely obtained by a partial nephectomy due to tumor location, size or patient morbidity, then safer surgical alternatives should be chosen. Even the most experienced kidney surgeon may choose radical nephrectomy for T1B or smaller tumors if the location is dangerous or the patient has comorbidity that is of concern. Active surveillance is also a valid alternative in select cases.

Howard N. Winfield, M.D.

Commentary

Ureteroscopy is increasingly used for the treatment of ureteral and renal calculi, and in many urology practices, it has become the treatment of choice for most stones. Improvements in instrumentation and techniques have led to greater stone-free rates and improved safety.¹ Instrumentation will continue to slowly improve, but attention has turned to other methods of enhancing patient outcomes following ureteroscopy. The use of tamsulosin to facilitate stone passage has led to “medical expulsive therapy.” Many studies have shown improved stone-free rates and less pain with the use of tamsulosin to aid in the passage of ureteral stones.^2–6 Others have shown benefit in the use of tamsulosin following ureteroscopy to decrease stent related pain.⁷ This study takes the next step and looks at outcomes after ureteroscopy for large (1–2 cm) stones with patients randomized to tamsulosin (40 patients) or control group (38 patients). The groups were fairly equivalent with regard to demographics and stone location. Follow-up was available for 73 patients (37 treatment group, 36 control). Stone-free status was well documented with a stone protocol CT scan in each patient 4 weeks after the procedure. The stone-free rate for the tamsulosin group (86.5%) was significantly better than that of the control group (69.4%). Likewise, the tamsulosin group had significantly fewer colicky episodes postoperatively than the control group (5.4% vs. 22.2%).

The results of this study make sense, given the distribution of alpha adrenergic receptors in the ureter, and the prior demonstration of the usefulness of tamsulosin for medical expulsive therapy. It would be interesting to know the stone-free rate at 3 months. Is it possible the control group would “catch up” to the tamsulosin group's stone-free rate? We do not know as this data was not measured. Also, pain medication usage and the validated “Ureteral Stent Symptom Questionnaire” were not measured and may have better quantitated the postoperative symptom benefit using tamsulosin. However, I believe this study is convincing enough to recommend the use of tamsulosin routinely after ureteroscopy for stones. It will be interesting to determine in the future if a drug which more selectively blocks alpha 1-D receptors (such as naftopidil) might further improve these results, given the greater distribution of alpha 1-D receptors in the proximal ureter.⁸

References

1. Preminger GM, Tiselius HG, Assimos DG, Alken P, Buck AC, Gallucci M, et al. 2007 guideline for the management of ureteral calculi. J Urol 2007;178:2418–2434.

2. Porpiglia F, Fiori C, Ghignone G, Vaccino D, Billia M, Morra I, et al. A second cycle of tamsulosin in patients with distal ureteric stones: a prospective randomized trial. BJU Int 2009;103:1700–1703.

3. Porpiglia F, Ghignone G, Fiori C, Fontana D, Scarpa RM. Nifedipine versus tamsulosin for the management of lower ureteral stones. J Urol 2004;172:568–571.

4. Sayed MA, Abolysor A, Adballa MA, El-Azab AS. Efficacy of tamsulosin in medical expulsive therapy for distal ureteral calculi. Scand J Urol Nephrol 2008;42:59–62.

5. Schuler TD, Shahani R, Honey RJ, Pace KT. Medical expulsive therapy as an adjunct to improve shockwave lithotripsy outcomes: a systematic review and meta-analysis. J Endourol 2009;23:387–393.

6. Wolf JS, Jr. Nifedipine versus tamsulosin for the management of lower ureteral stones. Int Braz J Urol 2004;30:339–340.

7. Wang CJ, Huang SW, Chang CH. Effects of tamsulosin on lower urinary tract symptoms due to double-J stent: a prospective study. Urol Int 2009;83:66–69.

8. Park HK, Choi EY, Jeong BC, Kim HH, Kim BK. Localizations and expressions of alpha-1A, alpha-1B and alpha-1D adrenoceptors in human ureter. Urol Res 2007;35:325–329.

Michael J. Conlin, M.D.

Validation of a high fidelity adult ureteroscopy and renoscopy simulator. White MA, DeHaan AP, Stephens DD, Maes AA, Maatman TJ, Michigan State University College of Osteopathic Medicine Urologic Consortium, Metro Health Hospital, Wyoming, MI.

J Urol 2010;183:673–677.

Purpose: Surgical simulation technology may efficiently train and accurately assess the acquisition of many skills. Surgical simulators often lack realism and can be expensive at $3,000 to more than $60,000. We assessed the face, content and construct validity of a newly developed, anatomically accurate, reasonably priced high fidelity ureteroscopy and renoscopy trainer.

Materials and Methods: A total of 46 participants, including attending urologists, urology residents, medical students and industry representatives, assessed the face and content validity of the simulator using a standard questionnaire. Ten experienced ureteroscopists with greater than 30 procedures per year and 10 novice ureteroscopists with 0 were assessed on the ability to perform flexible ureteroscopy, renoscopy and intrarenal basket extraction of a lower pole calculus using the adult ureteroscopy trainer (Ideal Anatomic Modeling, Holt, Michigan). Subject performance was assessed by an experienced ureteroscopist using a checklist, global rating scale and time to task completion.

Results: Of participants 100% rated the trainer as realistic and easy to use, and thought it was a good training tool, 98% thought that it would serve as a good training format and 96% would recommend it to urology trainees. All participants recommended it for use in residency programs and 96% would or would have used it during residency. Only 37.5% vs 100% of experienced vs novice ureteroscopists would use it to practice. Of participants 9% foresaw a problem with the trainer. On the trainer experienced ureteroscopists scored significantly higher on the global rating scale (mean ± SD 33.1 ± 1.3 vs 15.0 ± 2.7, p < 0.0001) and checklist (4.1 ± 1.0 vs 2.4 ± 1.1, p = 0.004), and required less time to complete the task (141.2 ± 40.1 vs 447.2 ± 301.7 seconds, p = 0.01).

Conclusions: Our preliminary study suggests the face, content and construct validity of the adult ureteroscopy trainer as a high fidelity ureteroscopy and renoscopy trainer.

DOI: 10.1016/j.juro.2009.10.013

Commentary

Surgical simulation for training makes sense and is slowly being adopted, primarily in the area of laparoscopy. Simulators for urologic laparoscopy, percutaneous surgery, and ureteroscopy are available. Cost remains a barrier for many training programs. While the use and cost of laparoscopic trainers can be shared across specialties, the cost of urologic-specific trainers must be borne by individual, generally small, urology departments. This has slowed the widespread adoption of simulation in urology.

This study evaluated the validity (face, content and construct) of a new high fidelity ureteroscopy simulator that is particularly cost-effective. This simulator is a silicone model based upon an actual patient's upper urinary tract reconstructed in 3 dimensions from a CT urogram. It was evaluated by 46 individuals, including attending urologists, urology residents, medical students, and industry representatives. Taken through the task of lower pole stone removal, the individuals were evaluated on time to task completion, task checklist, and a global rating scale. An initial survey was completed to determine face and content validity. The experienced ureteroscopists performed better than the novices in time to completion, checklist scores, and global ratings. This provides the construct validity. The authors point out the possible disadvantages of this system. This simulator is not computerized and thus cannot have a “virtual instructor.” It will require an actual instructor, which could be considered an additional cost for this simulator. Although it is inexpensive, the ureteroscopic instruments must be provided by the user. This could actually be considered an advantage by some in that the trainees would be trained on the devices that they will actually be using in that location's operating room, rather than being limited to the instrumentation either built into the trainer, or provided by the simulator's manufacturer. Lower cost training models such as this, despite its lack of “bells and whistles,” may allow more rapid adoption of these training opportunities into urology skills training

Michael J. Conlin, M.D.

Commentary

In an earlier report, Raman et al studied the natural history of residual fragments (RFs) following PCNL in 42 patients.¹ That report showed that size and location of the RFs correlate with subsequent stone-related events. Not surprisingly, larger fragments are more likely to require secondary surgical intervention and/or a visit to the ER. The group concluded a second look endoscopy may be beneficial for RFs larger than 2 mm and located in the renal pelvis or ureter.

Two points of interest have arisen from this earlier report. First, the impact of medical propulsion therapy (MET) with, for example, alpha blockers on ureteric RFs less than 4 mm would be of interest in view of recent reports. (During the study period, MET was not a variable option). Moving forward, MET may change the natural history of small ureteric and renal RFs and gives the urologist more options. Second, majority (47%) of RFs are located in the lower pole but these appear not have significant subsequent stone-related events unlike RFs in the ureter and renal pelvis. This could be explained the by non-passage but was not part of the endpoints of this earlier study.

In a follow-up paper noted here, the same excellent group of authors studied the cost comparison of immediate second look flexible nephroscopy (SLFN) versus expectant management for RFs post-PCNL. They concluded that, from a cost standpoint, in the context of a U.S. metropolitan hospital setting, the benefit of SLFN is seen only in RFs 4 mm or larger. They arrived at this conclusion by creating a cost model and combining data from 6 centers (including their own) to have accumulated data on 678 patients with a mean follow-up of 37 months. The obvious limitations to the paper include cost differences due to geographical locations and the inability to calculate cost during conservative management, e.g., work downtime and cost of medications, and so on. Despite numerous limitations of the study, the authors have come up with a well written paper to address cost containment issues with regard to management of RFs.

Reference

1. Raman JD, Bagrodia A, Gupta A, Bensalah K, Cadeddu JA, Lotan Y, et al. Natural history of residual fragments following percutaneous nephrostolithotomy. J Urol 2009;181:1162–1168.

Michael Y. C. Wong, MBBS

Commentary

This study concludes that ureteroscopy (URS) with intracorporeal lithotripsy is an acceptable treatment modality for all proximal ureteral calculi, especially stones >1 cm. For stones ≤1 cm, SWL is considered the treatment of choice. Outcome in the URS group was not influenced by stone size. In the SWL group, there was a significant difference in outcome: smaller stones yielded a significantly better effectiveness quotient than larger stones.

Another recent study confirms a better stone-free rate for proximal ureteral stones >1 cm with URS as compared to SWL.¹ The authors of this study also state that the outcome of URS is not influenced by stone burden or composition. In yet another study on proximal ureteral calculi <20 mm, there proved to be no significant difference in success rates with both treatment modalities.² The auxiliary procedure rate was equal for URS and SWL, but retreatment rate was significantly greater in the SWL group. Difference in complication rates was not significant, but SWL was significantly less invasive.

The debate on the best treatment modality for proximal ureteral stones remains open. One of the defining factors probably will be skill and experience—in endourologic procedures in general and URS specifically, and in the proper performance of SWL or “good lithotripsy.”

It is safe to state that training in endourologic procedures usually is taken very seriously, leading to more urologists achieving the skill to tackle proximal ureteral stones with URS. This is in stark contrast with training in SWL. Stone centers, and lithotripter companies for that matter, often fall short in providing proper training in SWL to their residents. Newer lithotripters too often are considered “plug and play” and the great importance of the skill, the experience, and the treatment strategies of the operator are grossly underestimated.

Ureteroscopy, even in skilled hands, remains more invasive and more prone to complications. Shockwave lithotripsy still is the least invasive treatment modality for ureteral stones and, given proper practice by an experienced urologist operating a high performance lithotripter, results may be comparably good.

References

1. Tawfiek ER. Treatment of large proximal ureteral stones: extracorporeal shock wave lithotripsy versus semirigid ureteroscope with lithoclast. UroToday Int J 2010;3:1.

2. Youssef RF, El-Nahas AR, El-Assmy AM, El-Tabey NA, El-Hefnawy AS, Eraky I, et al. Shock wave lithotripsy versus semirigid ureteroscopy for proximal ureteral calculi (<20 mm): a comparative matched-pair study. Urology 2009;73:1184–1187.

Geert G. Tailly, M.D.

Improved cost-effectiveness and efficiency with a slower shockwave delivery rate. Koo V, Beattie I, Young M, Stone Treatment Centre, Craigavon Area Hospital, Portadown, Northern Ireland, UK.

BJU Int 2009 Nov. 3 [epub ahead of print].

Objective: To determine the benefits of a slower shockwave (SW) delivery rate of 70 shocks/min on the treatment efficiency and cost effectiveness of extracorporeal SW lithotripsy (ESWL).

Patients and Methods: Patients who had ESWL for their upper urinary tract radio-opaque calculi were categorized into two groups: slow (70 SW/min) and fast (100 SW/min) delivery rate. All treatment was carried out using a lithotripter (Model S, Dornier MedTech, Wessling, Germany) as an outpatient procedure with no anaesthesia or sedation. The groups were followed for ≥6 months. The primary outcomes compared were the stone-free rate, re-treatment rate, additional procedure rate, perceived cost and actual cost. Clinical success was defined as stone-free status or asymptomatic insignificant residual fragments of <3 mm. Perceived cost was defined as the cost of ESWL alone, and actual cost included the cost of additional procedures and overhead costs to result in clinical success.

Results: In all, the study included 102 patients, categorized into the fast (51) and slow (51) rate groups. The groups were comparable in terms of sex, age, body mass index, stone size and stone location. The slow group had a significantly better stone-free rate (67% vs 25.5%, P = 0.002, chi-square), fewer mean shocks to clinical success (3045 vs 4414, P < 0.001, U-test), lower re-treatment rate (22% vs 45%, P = 0.013, chi -square), a lower additional procedure rate (12% vs 29%, P = 0.02, chi-square), greater efficiency quotient (0.51 vs 0.16) than the fast group. The mean perceived cost of ESWL (GB£ 297 vs £394, P = 0.013, U-test) and the mean actual cost of the slow group were significantly less (£496 vs £1002, P = 0.001, U-test).

Conclusion: Slowing the SW delivery rate to 70/min significantly reduced the actual cost by half and improved treatment efficiency.

DOI: 10.1111/j.1464–410X.2009.08919.x

Commentary

In terms of delivery rate of shockwaves, we have come full circle. At the onset of the practice of extracorporeal lithotripsy, considered by many to be a boring and tedious occupation, “the faster the better” was the motto. In the very beginning, shockwaves were ECG-triggered and it was the patient's heart rate that stipulated delivery rate. Soon we found out that in most cases an untriggered delivery was safe, so the need for speed revealed itself. Delivery rates up to 120 shocks per minute considerably speeded up treatments and improved turnover in lithotripsy centers.

Recent studies, both in vivo and in vitro, have changed our ideas on delivery rate of shockwaves.^1–4 These studies clearly demonstrated that a slower firing rate entailed better fragmentation, an improvement in stone-free rates and, last but not least, a reduction of the risk of adverse tissue effects caused by cavitation. These findings already were a good reason to review treatment strategies in favor of a slower delivery rate.

On top of this, this current study now takes away all remaining hesitation in slowing down treatments. The authors not only demonstrate a better stone-free rate, a lower retreatment rate, but a lower additional procedure rate and a better effectiveness quotient in the slow rate group. They also clearly demonstrate that the total cost per treatment and the total mean actual cost are lower in the slow rate group. Thus, a slower delivery rate delivers on all fronts: improved outcome, reduced adverse effects, and improved economics. Festina lente!

References

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

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

3. Weizer AZ, Zhong P, Preminger GM. New concepts in shock wave lithotripsy. Urol Clin North Am August 2007; 34:375–382.

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.

Geert G. Tailly, M.D.

Commentary

Transurethral incision of the prostate gland (TUIP) is often described as a simple procedure that is perceived as a less morbid surgical alternative to standard transurethral resection of the prostate gland (TURP) for treatment of symptomatic LUTS secondary to BPH. Generally, the procedure is reserved for relatively small prostates since debulking is not the end result of the procedure. This systematic and contemporary review and meta-analysis of short- and long-term data from randomized controlled trials comparing TUIP with TURP is one that summarizes and analyzes data from 795 randomized participants across 10 randomized controlled trials (RCTs). Notable is the attempt to classify the quality of the studies and to then objectively identify trends in the data reflective of the procedure as it compares to TURP. The authors considered the studies to be of moderate to poor quality. Of note, the findings of the authors are consistent with that generally experienced in clinical practice for the appropriately selected gland size. Selection is emphasized by their review, especially with regard to gland size. As expected, no differences in symptomatic improvement were seen between the two procedures. Not surprisingly, due to the minimal debulking effect, improvement in peak urine flow rate was lower for TUIP compared to TURP, while the rate of blood transfusion and TUR syndrome was higher after TURP. Additionally, TUIP is associated with a shorter operative duration and shorter hospital stay but a higher reoperation rate than TURP. As concluded by the authors, selecting TUIP involves a trade-off between the lower risk of perioperative morbidity with the higher risk of subsequent reoperation. Of note, the study does not address whether a single incision or dual incision or particular technique was utilized by the various studies. Additionally, there was a higher retreatment rate which seems to be due to reformation or healing of the incision, leading to a repeat TUIP. Overall, this analysis is a good contemporary reference for comparing TURP and TUIP since most of the studies reflect current practice patterns.

Alexis E. Te, M.D.

Effect of transurethral resection of the prostate on erectile function: a prospective comparative study. Jaidane M, Arfa NB, Hmida W, Hidoussi A, Slama A, Sorba NB, Mosbah F, Department of Urology, Sahloul University Hospital, Sousse, Tunisia.

Int J Impot Res 2009 Nov. 26 [epub ahead of print]

The effect of transurethral resection of the prostate (TURP) on erectile function is still controversial, and available evidence is conflicting. One of the possible mechanisms of post-TURP erectile dysfunction (ED) is direct thermal injury to the erectile nerves. The aim of this study was to investigate the effect of TURP on erectile function. Fifty patients undergoing TURP for obstructive benign prostatic hyperplasia (HBP) were prospectively included in the study, and 50 age-matched patients undergoing transurethral resection of the superficial bladder tumor were also prospectively included as a control group. All patients completed the international index of erectile function (IIEF-15), the international prostatic symptom score (IPSS) and the Hospital Anxiety and Depression Scale at inclusion in the study and then at the 3- and 6-month follow-up evaluation. Capsular perforations during TURP were prospectively reported by the operating surgeon. There was a significant improvement of erectile function in the TURP group despite the onset of ejaculation disorders in 70% of the patients. Improvement of erectile function was also found in the subgroup of patients with capsular perforation during TURP. Comparison with the control group showed that at preoperative evaluation, patients in the TURP group had more severe urinary symptoms and worse erectile function than did those of the control group. At the postoperative period, the IPSS score became comparable in the two groups, with major improvement of erectile function in the TURP group. We concluded that TURP improved erectile function in HBP patients with severe urinary symptoms. This improvement of erectile function was observed even in case of capsular perforation.

DOI: 10.1038/ijir.2009.56

Commentary

It has been long assumed that transurethral resection of the prostate (TURP) has a detrimental effect on erectile function because it is postulated that post-TURP erectile dysfunction (ED) is from direct thermal injury to the erectile nerves. However, it is now well known that untreated symptomatic BPH is associated with increased incidence of sexual dysfunction which is improved with medical therapy. There are few well done studies on the impact of TURP on sexual function that specifically investigate the effect of TURP on ED as an outcome parameter with validated sexual function outcome tools. Most studies report sexual dysfunction as an adverse event which would not always accurately report whether the dysfunction is present and to what degree. This study utilizes validated tools that better and more accurately define the presence and severity of the dysfunction.

In this study, 50 patients undergoing TURP for obstructive BPH were prospectively studied and compared to 50 age-matched patients undergoing transurethral resection of superficial bladder tumor who were prospectively included as a control group. All completed the International Index of Erectile Function (IIEF-15), the International Prostatic Symptom Score (IPSS) and the Hospital Anxiety and Depression Scale at inclusion in the study and then at the 3- and 6-month follow-up evaluations. Capsular perforations during TURP were documented. Surprisingly, the authors report a significant improvement of erectile function in the TURP group despite the onset of ejaculation disorders in 70% of patients treated with TURP. Improvement of erectile function was also found in the subgroup of patients with capsular perforation during TURP. Of note, the control group showed less severe urinary symptoms and erectile dysfunction preoperatively than the TURP treated group evaluation. The IPSS score as well as erectile function assessment became comparable in the two groups postoperatively with major improvement of erectile function in the TURP group compared to its preoperative baseline. This study well demonstrates that TURP improved erectile function in symptomatic BPH patients with severe urinary symptoms even in those with capsular perforation, and that the long-held bias that it causes ED is false.

Alexis E. Te, M.D.

Commentary

Kidney stone formation is usually secondary to an interaction between genetic and environmental factors. Diet is considered the most important dietary factor and it has been demonstrated that dietary modifications may attenuate stone risk. These investigators demonstrated in 3 large epidemiologic cohorts that subjects who eat “cardiovascular friendly foods” are less apt to develop kidney stones. The take-home message is that stone formers should eat “healthy” by consuming more fruits, vegetables and low fat dairy products, and limit sodium and animal protein consumption!

Dean G. Assimos, M.D.

Gastric band placement for obesity is not associated with increased urinary risk of urolithiasis compared to bypass. Penniston KL, Kaplon DM, Gould JC, Nakada SY, Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, WI.

J Urol 2009;182:2340–2346.

Puspose: Obesity is associated with multiple health risks. Bariatric surgery is a treatment for clinically severe obesity and is known to increase urolithiasis risk. However, trends in risk over time are not well characterized. Moreover little attention has been devoted to laparoscopic gastric band placement. A comparison of urinary risk of urolithiasis after the Roux-en-Y and gastric banding procedures was performed.

Materials and Methods: We evaluated 24-hour urine collections from 39 subjects (11 male and 28 female, mean age 51 years) after bariatric surgery. Of these subjects 27 underwent Roux-en-Y gastric bypass and 12 had gastric banding procedures. Mean time since surgery was 3.4 and 2.1 years for the Roux-en-Y gastric bypass and gastric banding groups, respectively.

Results: Urine volume was low in both groups (less than 1.5 l daily). Urinary calcium excretion was lower (p = 0.001) in the Roux-en-Y gastric bypass (100 mg daily) vs the gastric banding group (191 mg daily). After Roux-en-Y gastric bypass surgery 48% had a urinary oxalate of 45 mg daily or more compared to 25% after gastric banding. Urinary citrate was less than 370 mg daily for 14 subjects in the Roux-en-Y gastric bypass and 1 in the gastric banding group. All patients were taking calcium supplements. Dietary intake of high oxalate foods did not correlate with urinary oxalate excretion or with hyperoxaluria.

Conclusions: Our study confirms the risk of urinary stones following the Roux-en-Y gastric bypass procedure as a result of hyperoxaluria, low urine volume and hypocitraturia. Those with gastric banding placement had low urine volumes. Future studies should elucidate the effect of nutrition and/or pharmacological therapy on stone risk of both surgeries as their incidence increases.

DOI: 10.1016/j.juro.2009.07.041

Commentary

There is an obesity epidemic in the United States and other parts of the world. Obesity is a risk factor for both uric acid and calcium oxalate stone formation. The performance of bariatric surgery for treating morbid obesity has been steadily increasing as it has been demonstrated to limit morbidity and mortality in this population. Gastric bypass has been demonstrated to increase stone risk.¹ The development of hyperoxaluria after this procedure has been thought to be one of the reasons for this occurrence.^2,3 These investigators found that patients subjected to a gastric banding procedure were less apt to develop hyperoxaluria. One group recently reported that gastric banding does not increase kidney stone risk.⁴ Therefore, gastric banding may be the preferred approach in morbidly obese patients with a history of kidney stones who are considering bariatric surgery.

References

1. Matlaga BR, Shore AD, Magnuson T, Clark JM, Johns R, Makary MA. Effect of gastric bypass surgery on kidney stone disease. J Urol 2009;181:2573–2577.

2. Sinha MK, Collazo-Clavell ML, Rule A, Milliner DS, Nelson W, Sarr MG, et al. Hyperoxaluric nephrolithiasis is a complication of Roux-en-Y gastric bypass surgery. Kidney Int 2007;72:100–107.

3. Patel BN, Passman CM, Fernandez A, Asplin JR, Coe FL, Kim SC, et al. Prevalence of hyperoxaluria after bariatric surgery. J Urol 2009;181:161–166.

4. Semins MJ, Matlaga BR, Shore AD, Steele K, Magnuson T, Johns R, et al. The effect of gastric banding on kidney stone disease. Urology 2009;74:746–749.

Dean G. Assimos, M.D.

Commentary

Renal cryotherapy for small kidney masses has become an acceptable alternative to surgical excision at many medical centers. In fact, it is even a recommendation as treatment for patients with clinical T1a tumors and major medical comorbidities in the recently published AUA Guidelines for patients with clinical T1 renal masses.¹ Although still debated, it is generally felt that a consistent temperature during cryoablation of at least −20°C should be achieved to cause cellular necrosis and adequate tumor death.

Young et al examined 2 current commercially available cryoablation probes (Endocare 1.7 mm CryoProbe™ and Galil 1.47 mm IceRod™) to determine if the recommended isotherms based on gel models correlated to ex vivo and in vivo isotherms in a porcine model. Temperatures at the cryoprobe were not significantly different along the probe in any medium for either system. However, away from the probe, ex vivo and in vivo trials showed warmer temperatures toward the cryoprobe tip for each system. Mean temperatures 5 mm distal to the tip in vivo was 19.2°C for CryoProbes and 27.3°C for IceRods. At almost all sites temperatures were significantly colder in gel and in ex vivo kidney than in the in vivo kidney for both probes.

The authors determined that gel and ex vivo isotherms do not predict the in vivo pattern of freezing and should not be used for preoperative planning. The cryoprobe should also be passed 5 mm distal to the tumor border to achieve suitable temperatures at the margin. Multipoint thermal sensor probes are recommended to record actual temperature during renal cryotherapy.

I think this study makes some very important discoveries when considering how to successfully treat kidney cancer with cryoablative technologies. Most manufacturer recommendations are based on gel models. However, in this study neither cryoablation system achieved consistent temperatures of −20°C at each point in vivo even along the 10 mm isotherm. Therefore, we cannot simply rely on the proposed “ice ball” kill zone, but need to use real-time thermal sensor monitoring during cryoablation to ensure we are adequately treating the targeted lesion. Although not addressed in this study, it also has implications for treatment techniques during cryoablation of the prostate.

References

1. Novick AC, Campbell SC, Belldegrun A, Blute ML, Chow GK, Derweesh IH, et al. Guideline for the Management of the Clinical Stage 1 Renal Mass. American Urological Association Education and Research, Inc.; 2009.

David A. Duchene, M.D.

Next generation biodegradable ureteral stent in a Yucatan pig model. Chew BH, Lange D, Paterson RF, Hendlin K, Monga M, Clinkscales KW, Shalaby SW, Hadaschik BA, Stone Centre at Vancouver General Hospital, Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada.

J Urol 2010;183:765–771.

Purpose: Ureteral stents are commonly used to facilitate kidney drainage but they may produce significant stent symptoms and morbidity, and require a secondary procedure for removal. Previous biodegradable stents showed bio-incompatibility or inconsistent degradation, requiring extra procedures to remove undegraded stent fragments. We previously reported a first generation biodegradable stent composed of suture-like material that required placement through the lumen of a sheath and degraded by 10 weeks. We now report second and third generation biodegradable stents that degrade more rapidly and can be placed directly over a polytetrafluoroethylene guidewire.

Materials and Methods: Two groups of 16 Yucatan pigs each were unilaterally stented endoscopically with a control nondegradable (biostable) stent or a second generation degradable Uriprene® stent. Blood studies, renal ultrasound and excretory urography were done throughout the study to determine renal function, hydronephrosis and stent degradation. Genitourinary organs were harvested at necropsy for pathological analysis. A third generation stent designed to improve degradation time was bilaterally implanted endoscopically into 4 Yorkshire Farm pigs (total of 8 stents), followed by excretory urography weekly to assess degradation and kidney function. Biomaterial parameters were tested.

Results: Second generation stents began degrading at 2 weeks and were completely degraded by 10 weeks. All third generation stents were degraded by 4 weeks. Hydronephrosis was considerably less in the Uriprene group than in control biostable stented kidneys. Biostable stented ureters showed an average higher degree of inflammation, uropathy and nephropathy. Physical characteristics indicate that Uriprene stents are significantly more resistant to stent compression and have markedly higher tensile strength and coil strength comparable to that of other commercially available plastic stents.

Conclusions: Our study confirms that Uriprene stents are biocompatible and provide good renal drainage. They hold promise for decreasing the need for a secondary procedure and stent related morbidity, such as infection and irritative symptoms.

DOI: 10.1016/j.juro.2009.09.073

Commentary

Ureteral stents are often necessary to facilitate temporary kidney drainage in episodes of stone obstruction or following lithotripsy procedures. As all urologists are well aware, ureteral stents are a significant cause of patient morbidity and often require a separate procedure to remove them. Forgotten stents can lead to even more problems of kidney obstruction and kidney failure, since they are prone to encrustation and infection. A biodegradable stent would help eliminate the problem of a forgotten stent and the need for an additional patient procedure. Previous biodegradable stent designs have had problems of inconsistent degradation and biological incompatibilities leading to more difficulties than benefits for the patient.

Chew et al expand on previous work by investigating a second (and third) generation version of their degradable Uriprene^® stent. Uriprene is an elastic, absorbable matrix, reinforced composite constructed of copolyester components. The first generation stent required placement through the lumen of a 10F sheath and took 10 weeks to degrade (which was felt to be too long). The polymers have been adjusted to hasten degradation time and improve axial rigidity so they can be inserted directly over a polytetrafluoroethylene guidewire without a ureteral sheath.

In this study, second generation Uriprene stents were evaluated against a control nondegradable (biostable) stent in 2 groups of 16 Yucatan pigs. Blood studies, renal ultrasound, and excretory urography were done throughout the study to determine renal function, hydronephrosis and stent degradation. The second generation stents began degrading by 2 weeks and were completely degraded by 10 weeks. Hydronephrosis was seen less in the Uriprene stent group, which also had less inflammation, uropathy, and nephropathy than the biostable stented ureters. The physical characteristics of Uriprene stents showed better resistance to stent compression and had higher tensile strength than the biostable group, but also had much higher intragroup variance than the biostable group. Eight third generation stents (designed to further reduce degradation time) were implanted into 4 Yorkshire pigs and were degraded by 4 weeks. The authors concluded that Uriprene stents are biocompatible and provide good renal drainage in a porcine model.

The results of this experiment are encouraging in that we are coming closer to the development of a commercially available biodegradable stent. An interesting aspect of these stents is that they are designed to degrade from the distal to proximal end to avoid obstruction from degradation products of the proximal end of the stent. Many more modifications are yet to be made, and these studies will have to be confirmed in a human model and clinical studies. However, the Uriprene stent appears to have great promise as a biodegradable stent in the near future.

David A. Duchene, M.D.

Commentary

This is a robust study from Dr. Smith's group, as these authors are highly experienced surgeons with tremendous volume in radical retropubic prostatectomies (ORP) and robot-assisted laparoscopic prostatectomies (RRP). In this study, the authors compared 491 ORP to 1,413 RRP with a median follow-up of 10 months. On univariate analysis, RRP demonstrated a slightly lower risk for biochemical recurrence (BCR). The authors conclude that surgical approach was not a significant predictor of BCR in the multivariate model and both RRP and ORP were effective.

RRP is a highly exciting and scintillating subject as it has challenged the hitherto commonly performed open retropubic radical prostatectomy and the less utilized laparoscopic radical prostatectomy. However, the usual questions are posed—whether it gives better, worse or equivalent long-term cancer control than traditional methods such as ORP. RRP has grown at a nearly unprecedented rate. The variations in the functional outcome and oncological efficacy of this procedure are chiefly due to surgical experience, tumor grade, stage, and high volume centers. RRP was initially developed by Dr. Menon, which he fondly calls the Vattikuti Institute prostatectomy (VIP) technique. This technique was published in 2004 after performing over 1000 cases¹, which led several leaders to mull over and adopt, but with their own modification, though the basic tenet remains same. There is scant reporting on the long-term oncological results of RRP. The largest report to date, of 2,766 patients undergoing RRP, has the longest follow-up to data.² In this study, data were collected prospectively including demographic, surgical, oncologic, and functional outcomes with up to 5-year follow-up. At a median follow-up of 22 months, 7.3% of men had a PSA recurrence. The 5-year actuarial biochemical free survival rate was 84%.

The studies from the Smith and Menon groups are seminal and echo the fact that cancer can be cured equally with RRP and ORP. But, the key to success is surgical experience, skill set and high volume.

References

1. Menon M, Hemal AK. Vattikuti Institute prostatectomy: a technique of robotic radical prostatectomy: experience in more than 1000 cases. J Endourol 2004;18:611–619.

2. Badani KK, Kaul S, Menon M. Evolution of robotic radical prostatectomy: assessment after 2766 procedures. Cancer 2007;110:1951–1958.

Ashok K. Hemal, M.S., M.Ch.

Robotic-assisted laparoscopic intracorporeal urinary diversion. Pruthi RX, Nix J, McRackan D, Hickerson A, Nielsen ME, Raynor M, Wallen E, Division of Urologic Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, NC.

Eur Urol 2010 Jan. 9 [epub ahead of print]

Background: Recent small case series have now been reported for robotic-assisted laparoscopic radical cystectomy (RALRC). In most of these series, the urinary diversion has been performed in an extracorporeal fashion. There have been few case reports of an intracorporeal diversion and little description of the technique of such a procedure.

Objective: In this paper, we report our initial experience with robotic-assisted laparoscopic intracorporeal urinary diversion, describing stepwise the surgical procedure itself and evaluating perioperative and pathologic outcomes of this novel procedure.

Design, Setting, and Participants: We studied a single-institution case series of patients undergoing robotic-assisted cystectomy and intracorporeal urinary diversion for clinically localized urothelial carcinoma of the bladder (n = 10) or for a noncompliant dysfunctional bladder refractory to more conservative management (n = 2). Historical comparisons are also made to a consecutive case series of 20 patients undergoing robotic radical cystectomy and extracorporeal urinary diversion.

Surgical Procedure: RALRC and intracorporeal urinary diversion, including ileal conduit (n = 9) and orthotopic ileal neobladder (n = 3).

Measurements: The stepwise operative procedure is described in detail. Outcome measures evaluated in this series included operative variables, hospital recovery, and complication rate. Comparisons were made to a contemporaneous series of 20 patients who underwent a robotic cystectomy with extracorporeal diversion during this time period (from an experience of >100 robotic cystectomy patients since 2005).

Results and Limitations: Twelve patients (mean age: 60.9 yr) underwent an intracorporeal diversion. Mean operating-room time of all patients was 5.3 h, and mean surgical blood loss was 221 ml. Mean time to flatus, bowel movement, and hospital discharge was 2.2 d, 3.2 d, and 4.5 d, respectively. Eleven of the 12 patients were discharged on or before postoperative day 5. There were six postoperative complications in five patients (42%), with one complication being Clavien grade 3 or higher. The major limitations of the study are the small sample size and the nonrandomized nature of the compared treatment groups (intracorporeal vs extracorporeal), which limits the ability to directly compare the techniques at a high level of scientific confidence.

Conclusions: Our initial experience with robotic-assisted laparoscopic intracorporeal diversion appears to be favorable with acceptable operative and short-term clinical outcomes.

DOI: 10.1016/j.eururo.2009.12.028

Commentary

In this paper, Pruthi and coauthors have presented their initial experience with robotic-assisted laparoscopic intracorporeal urinary diversion, describing a stepwise surgical procedure and evaluating perioperative and pathologic outcomes. This series is comprised of 10 patients with carcinoma of the bladder and 2 patients with noncompliant dysfunctional bladder. Ileal conduit and orthotopic ileal neobladder urinary diversions were performed in 9 and 3 patients, respectively. The operative steps of this procedure are described nicely in an educative fashion. I would like to congratulate the authors for their innovative work.

While evaluating perioperative outcomes, they report 6 complications in 5 patients within 30 days of surgery and 2 additional patients had Clavien grade 2 at 90 days follow-up. Hospital readmission was required in 2 patients.

In summary, this is a non-randomized small study demonstrating technical steps on selected patients, with short-term follow-up. Initial data are encouraging but it lacks long-term outcomes.

Ashok K. Hemal, M.S., M.Ch.

Commentary

This study by Littrup et al is a simple yet well-crafted study evaluating isotherm formation using cryoprobes 2.4 mm and smaller in both a single and multiple fashion and in various geometric configurations. The authors created a mechanical jig in which cryoprobes and multiple thermocouples could be reliably placed in agar that was kept at three different temperatures, with the highest being 39°C. The isotherms were measured using thermocouples placed at 0.5, 1.0, and 1.5 cm away from the cryoprobes as well as at the periphery of the agar mold, and the ice balls were correspondingly visualized using sonography as well as computed tomography. Because of multiple artifacts produced by the probes and thermocouples, sonography was not very useful and could not facilitate visualization of the posterior aspects of the ice balls. Therefore, computed tomography provided the most useful images, which were also used to accurately confirm the locations of the probes and thermocouples. Overall, the authors performed a total of 4,056 individual temperature measurements in 24 experiments.

Some very valuable information can be gleaned from this data by anyone who performs cryoablation, whether of the prostate, kidney, liver or lung. Notably, use of 2.4 mm cryoprobes produced larger and faster ice balls than did use of 1.7 mm probes, although this could be overcome by using more of the smaller cryoprobes. For example, using four cryoprobes, the total:lethal ice ratios were similar for the two probe sizes. Additionally, the authors looked at different configurations–linear and triangular–showing that a triple configuration of 2.4 mm cryoprobes produced a lethal ice ball at 10 minutes, whereas a triple configuration of 1.7 mm cryoprobes did so at 15 minutes. Additionally, a linear configuration of two probes produced an oval lesion, which may increase the risk of incomplete lethal coverage along the short axis for a round lesion. This information is very useful, as many renal tumors are circular, whereas some are irregular or grow endophytically at obtuse angles into the kidney. These irregularly shaped tumors are the most likely to recur if not properly covered by a well-shaped ice ball.

The authors chose a −30°C isotherm as the target temperature for cytotoxicity because this temperature conforms to the clinical application for most tissues. The authors also found that the greatest increase in lethal ice ball percentage for both 1.7 and 2.4 mm cryoprobes was obtained when adding a second probe, although they observed a continual large increase after adding a third 1.7 mm cryoprobe. The incremental increase in lethal ice ball percentage with the addition of more probes after the third was not quite as dramatic but was larger. The authors also confirmed that the cytotoxic margin was consistently no more than 1 cm behind the leading edge of ice. Interestingly, this was a little larger than the commonly accepted 0.5 cm margin and may have resulted from different conductivity of the agar and human tissues or it may represent a more accurate measurement by this group. The original publication contains excellent images showing the geometry of the isotherms in these various configurations.

In summary, this article contains some excellent points made by the authors, whom I believe have approached this subject in a very objective fashion and readily recognized the limitations of their study design, such as the lack of a heat sink (no vasculature) and the different conductivity of agar and tissues (such as encountered in the kidney, liver and lung). Another limitation that was not mentioned is the risk of ice ball fracture in human tissues. Although not unusual and certainly quite problematic in clinical practice, this risk arguably increases with the use of more than one probe. Based on the data, the authors recommended the use of multiple probes to overcome the effects of an increased heat load, such as that potentially encountered near large vessels, and of 2.4 mm cryoprobes to generate the same amount of lethal ice but in a shorter period of time, as increased freeze rates are associated with increased cytotoxicity. The authors also propose that further work is needed to define the effects of probe spacing at 1.0 and 1.5 cm on isotherms but that spacing greater than 2.0 cm should not be explored because it has not produced lethal ice between probes in other experiments using normal tissue. This is an elegant study and should contribute significantly to our understanding of cryoablation isotherms in clinical practice.

Surena F. Matin, M.D.

Immunological response to renal cryoablation in an in vivo orthotopic renal cell carcinoma murine model. Matin SF, Sharma P, Gill IS, Tannenbaum C, Hobart MG, Novick AC, Finke JH, Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX.

J Urol 2010;183:333–8.

Purpose: The immunological consequences of cryoablation for renal cell carcinoma are largely unknown. Cryoablation is an attractive therapeutic option for tumors due to its minimally invasive nature. Cryoablation is also potentially immunogenic. We describe the development of an animal model to deliver in vivo renal cryotherapy to orthotopically implanted renal cell carcinoma and the results of multiple immunological interrogations after cryoablation.

Materials and Methods: Four to 6-week-old female Balb/c mice (Jackson Laboratories, Bar Harbor, Maine) underwent renal subcapsular implantation of the syngeneic murine renal cell carcinoma Renca. Two weeks later contact cryoablation was done in tumor bearing kidneys. Another group of animals underwent cryoablation of normal kidneys. Animals were sacrificed 2 weeks after tumor injection or 1 and 2 weeks after cryoablation, respectively. Kidneys, spleens and draining lymph nodes were harvested. Evaluation consisted of immunohistochemistry, immunofluorescence and gene expression profiling using reverse-transcriptase polymerase chain reaction.

Results: Subcapsular tumor implantation was successful in all cases and confirmed histologically. No significant lymphocytic infiltrate was seen in tumor only animals but those treated with cryoablation (tumor and nontumor bearing) had a significant inflammatory response primarily in sublethal tissue injury and perivascular areas. After cryoablation most infiltrating cells were neutrophils, macrophages and T cells. Polymerase chain reaction showed increased interferon-γ production in kidneys after cryoablation.

Conclusions: This study shows the potential feasibility of this animal model for studying cryo-immunology. We confirm the absence of any significant immune cell infiltration in tumor bearing kidneys and report a significant inflammatory infiltrate after cryoablation, consisting primarily of neutrophils, macrophages, and CD4+ and CD8+ T cells with an increase in the T helper type 1/2 ratio. This orthotopic murine model can form the basis of future studies of additional immunological aspects of renal cryoablation.

DOI: 10.1016/j.juro.2009.08.110

Commentary

The immunologic consequences of cryoablation are potentially very interesting, given the potential of cryoablation to stimulate inflammatory responses and, subsequently, antitumor immunologic responses. Research of this subject is hampered due to absence of an animal model with syngeneic kidney cancer that underwent cryoablation. Past studies of cryoablation have used normal large animals to examine the mechanics and safety of cryoablation, small animals with implanted non-renal tumor grafts to evaluate cytotoxicity and efficacy, and in vitro models to assess oncologic kinetics. Therefore, the study by Matin et al is significant in that multiple immunologic interrogations were performed in an in vivo orthotopic animal model with a syngeneic renal cell carcinoma, which does not cause an immunologic response by itself (Renca, a mouse renal cell carcinoma cell line, implanted in Balb/C mice kidneys). Two weeks after implantation, the investigators either sacrificed mice or performed cryoablation of tumor-bearing kidneys. A third arm consisted of mice with normal kidneys undergoing cryoablation. The researchers sacrificed the remaining animals 2 weeks after cryoablation and harvested kidney tissue for immunologic studies, including immunohistochemistry, immunofluorescence, and gene expression profiling. Evaluation of kidneys with only implanted tumors confirmed the absence of inflammatory infiltrates. However, the cryoablated kidneys of mice with and without tumors had significant inflammatory responses in the margins of the zones of ablation as well as in perivascular spaces, indicating active recruitment of inflammatory cells. Most of these cells were neutrophils, but significant numbers of macrophages and T cells were also present. The authors also showed a shift in the T-helper type 1 and type 2 ratio, with higher interferon-γ production after cryoablation, indicating a potentially favorable antitumor response. Identified T-cell subtypes included CD4+ and CD8+ T cells.

How is this information useful? First, it confirms the notion that cryoablation can stimulate an inflammatory response, suggesting also that this is likely responsible for some imaging changes seen in clinical practice, such as the halo sign and other changes seen in post-therapy imaging. Second, it indicates that this is a ripe area for further research, as this inflammatory response can be harnessed as a catalyst that, with further addition of immunostimulatory agents, could result in an antitumor response. Clearly, in the majority of patients with kidney cancer undergoing cryoablation, this antitumor response does not occur; otherwise, metastatic disease would be routinely cured simply by performing cryoablation of one tumor. However, case reports have shown that some patients with biopsy-proven metastatic disease rarely have complete remission after ablative therapy. What is it about these patients' tumors or their immune milieus that allows for such dramatic clinical responses? These are very interesting areas for further research, with current human studies designed to evaluate the immunologic repertoire and use of possible combination strategies for treatment of kidney cancer.

Surena F. Matin, M.D.