Survey of Endourology

Laparoscopy

Randomized controlled trial comparing laparoscopic and robot-assisted radical prostatectomy. Porpiglia F, Morra I, Lucci Chiarissi M, Manfredi M, Mele F, Grande S, Ragni F, Poggio M, Fiori C, Division of Urology, San Luigi Gonzaga Hospital-Orbassano (Turin), University of Turin, Turin, Italy.

Eur Urol 2012; Jul. 20 [epub ahead of print].

Background: The advantages of robot-assisted radical prostatectomy (RARP) over laparoscopic radical prostatectomy (LRP) have rarely been investigated in randomised controlled trials.

Objective: To compare RARP and LRP in terms of the functional, perioperative, and oncologic outcomes. The main end point of the study was changes in continence 3 mo after surgery.

Design, Setting and Participants: From January 2010 to January 2011, 120 patients with organ-confined prostate cancer were enrolled and randomly assigned (using a randomisation plan) to one of two groups based on surgical approach: the RARP group and the LRP group.

Intervention: All RARP and LRP interventions were performed with the same technique by the same single surgeon.

Outcome Measurements and Statistical Analysis: The demographic, perioperative, and pathologic results, such as the complications and prostate-specific antigen (PSA) measurements, were recorded and compared. Continence was evaluated at the time of catheter removal and 48h later, and continence and potency were evaluated after 1, 3, 6, and 12 mo. The student t test, Mann-Whitney test, χ(2) test, Pearson χ(2) test, and multiple regression analysis were used for statistics.

Results and Limitations: The two groups (RARP: n=60; LRP: n=60) were comparable in terms of demographic data. No differences were recorded in terms of perioperative and pathologic results, complication rate, or PSA measurements. The continence rate was higher in the RARP group at every time point: Continence after 3 mo was 80% in the RARP group and 61.6% in the LRP group (p=0.044), and after 1 yr, the continence rate was 95.0% and 83.3%, respectively (p=0.042). Among preoperative potent patients treated with nerve-sparing techniques, the rate of erection recovery was 80.0% and 54.2%, respectively (p=0.020). The limitations included the small number of patients.

Conclusions: RARP provided better functional results in terms of the recovery of continence and potency. Further studies are needed to confirm our results.

Copyright © 2012. Published by Elsevier B.V.

DOI: 10.1016/j.eururo.2012.07.007

Commentary

These authors report the clear-cut conclusion that robotic-assisted radical prostatectomy (RARP) resulted in better postoperative continence than laparoscopic radical prostatectomy (LRP) using a prospective, randomized controlled trial (RCT) design in a single institution. All operations were performed by a single surgeon. The importance of this paper comes from the following two points: it is the second RCT on RARP vs. LRP in the world, and it is a good quality study. Among the 129 patients who were assessed for eligibility (all patients who underwent radical prostatectomy due to T1-2N0M0), only 7 were excluded (previous radiation or hormonal therapy or transurethral resection of the prostate) and 2 declined to participate. All patients were evaluated postoperatively for 1 year without any lost to follow-up. The surgeon is highly experienced, with more than 600 LRPs performed. The average operation time of the LRP was 138±29.7 minutes (mean±S.D.), including those patients who underwent an extended pelvic lymphadenectomy and nerve-sparing, in 22% and 58% of the cases, respectively. There were no major postoperative complications in either group.

Continence rates, defined as none or 1 safety pad, for RARP and LRP in this study were 80.0 and 61.6% at 3 months postoperatively, and 95.0 and 83.3% at 1 year postoperatively, (respectively) which was a statistically significant difference (p=0.027). The continence rate for LRP was similar to values from previous reports.

Another interesting point in this paper is that RARP demonstrated a shorter operative time than LRP only for urethrovesical anastomosis (12.0 vs 15.4 minutes, respectively). RARP required a longer time for apical and urethral dissection (35.5 vs 30.7 minutes, respectively). This may be due to the limited experience with RALP for this surgeon (100 cases). It is expected that the quality of the RARP would be better as experience increases.

The other RCT on RARP vs LRP was performed by Asimakopoulos et al in 128 patients who underwent bilateral intrafascial nerve-sparing radical prostatectomy.¹ Those authors failed to show an advantage for RARP in continence rates, but showed a significantly higher rate of capability of intercourse in RARP as compared to LRP (77% vs 32%, p<0.0001).

The main question regarding the current paper is whether the conclusion can be applied to other surgeons with different experiences in laparoscopic or robotic surgeries and/or with different methods in performing the procedures, as discussed by Touijer² and the current authors.³ However, this study should be valuable in evaluating the effects of introducing surgical robots for radical prostatectomy for experienced laparoscopic surgeons, because multi-institutional mega-studies using RCTs on surgical procedures are not realistic.

References

1. Asimakopoulos AD, Pereira Fraga CT, Annino F et al. Randomized comparison between laparoscopic and robot-assisted nerve-sparing radical prostatectomy. J Sex Med 2011;8:1503–12.

2. Touijer KA. The promise and challenges of randomized controlled trials for surgical interventions. Eur Urol 2012; Aug. 19 [epub ahead of print].

3. Porpiglia F, Fiori C. Reply from Authors re: Karim A. Touijer. The promise and challenges of randomized controlled trials for surgical interventions. Eur Urol 2012; Sep. 25 [epub ahead of print].

Tadashi Matsuda, MD

Transperitoneal laparoscopic ureterolithotomy versus retroperitoneal laparoscopic ureterolithotomy: a prospective randomized comparison study. Singh V, Sinha RJ, Gupta DK, Kumar M, Akhtar A, Department of Urology, C.S.M. Medical University, Uttar Pradesh, India.

J Urol 2012; Sep. 27 [epub ahead of print].

Purpose: To compare Laparoscopic transperitoneal and retroperitoneal ureterolithotomy approaches and to find out whether one technique is superior over the other.

Materials and Methods: In this prospective randomized study, from January 2009 to May 2012, 48 patients of proximal or midureteric stones were subjected either to transperitoneal laparoscopic ureterolithotomy (TPLU) or retroperitoneal laparoscopic ureterolithotomy (RPLU). The randomization was on 1:1 basis. The group I and group II consisted of patients underwent TPLU and RPLU respectively. Demographic, clinical characteristics and postoperative data were collected and analysed. The statistical analysis was done on SPSS version 15.0 using Fisher exact and Mann Whitney-U tests. The p value<0.05 considered statistically significant.

Results: The difference in visual pain analog score (VAS) and mean tramadol requirement on day 1 and day 2 between two groups was statistically significant and higher in group I (p<0.05). The post-operative hospital stay and paralytic ileus were significantly higher in group I (p<0.05). The differences in total operating time and intra-corporeal suturing time between two groups were statistically insignificant. However, the successful stone removal was equal in two groups.

Conclusions: For proximal or midureteric large and impacted stones, TPLU is significantly associated with pain, higher dose of tramadol requirement, ileus and longer hospital stay in comparison to RPLU. However the successful stone removal remains same in both the groups.

Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

DOI: 10.1016/j.juro.2012.09.114

Commentary

This paper is important because the advantages of the retroperitoneal approach (RA) are shown in laparoscopic ureterolithotomy over the transperitoneal approach (TA) by a prospective randomized study, with similar operative outcomes and technical difficulties. Even though the number of patients is limited due to the difficulties of randomized studies in evaluating surgical procedures, the RA group had less postoperative pain, a shorter hospital stay and a lower incidence of postoperative paralytic ileus of absent bowel sounds for more than 36 hours.

In the era of transureteral ureterolithotomy, laparoscopic ureterolithotomy is seldom performed in Westernized countries. However, it should be beneficial for patients with large or impacted stones, particularly for those countries in the stone belt. The advantages of RA over TA shown in this study may be minimal, but they are nonetheless important. The benefits of postoperative pain after laparoendoscopic single-site surgery (LESS), which were demonstrated by randomized studies, are similar to or less than those shown in this paper.

Furthermore, many other popular urologic laparoscopic surgeries are performed using either RA or TA, such as pyeloplasty, adrenalectomy, partial nephrectomy and nephrectomy. Few prospective randomized studies have been published comparing these two approaches. Rubinstein et al compared RA and TA for laparoscopic adrenalectomies on 57 patients, and reported similar operative times, estimated blood loss, complication rates and hospital stay, analgesic requirements, and incidence of paralytic ileus.¹ However, they showed a shorter convalescence of 2.3 weeks for RA as compared to TA (4.7 weeks). RA and TA pyeloplasties were compared by Shoma et al in 40 patients, and similar hospital stays, convalescence and success rates were shown, although the operation time was longer in RA.² These authors did not evaluate the analgesic requirements and postoperative pain because epidural analgesia was routinely used. Desai et al evaluated the differences between RA and TA laparoscopic radical nephrectomies in 102 patients.³ They showed that RA resulted in similar estimated blood loss, hospital stays and analgesic requirements, although the operation time was shorter for RA than for TA. Nambirajan et al also showed similar analgesic use and hospital stays by evaluating these two approaches on 40 nephrectomy patients.⁴ However, Nadler et al demonstrated a shorter hospital stay and time to resume normal daily activity in the TA group than the RA group, probably due to the flank extraction excision in RA.⁵ Therefore, extraction excision may have a stronger influence on postoperative pain and convalescence than the method of approach—RA vs. TA—in procedures where a large specimen needs to be extracted, such as a nephrectomy. According to the results of this study and the study by Rubinstein et al, RA may have the advantages of less postoperative pain and shorter convalescence over TA in procedures without minimal or no elongation of wounds to extract the surgical specimens. RA, which was originally developed by Gaur⁶, could be used more widely in urologic laparoscopic surgeries. Further study is necessary to draw conclusions.

References

1. Rubinstein M, Gill IS, Aron M et al. Prospective, randomized comparison of transperitoneal versus retroperitoneal laparoscopic adrenalectomy. J Urol 2005;174:442–5.

2. Shoma AM, El Nahas AR, Bazeed MA. Laparoscopic pyeloplasty: a prospective randomized comparison between the transperitoneal approach and retroperitoneoscopy. J Urol 2007;178:2020–4.

3. Desai MM, Strzempkowski B, Matin SF et al. Prospective randomized comparison of transperitoneal versus retroperitoneal laparoscopic radical nephrectomy. J Urol 2005;173:38–41.

4. Nambirajan T, Jeschke S, Al-Zahrani H et al. Prospective, randomized controlled study: transperitoneal laparoscopic versus retroperitoneoscopic radical nephrectomy. Urology 2004;64:919–24.

5. Nadler RB, Loeb S, Clemens JQ et al. A prospective study of laparoscopic radical nephrectomy for T1 tumors–is transperitoneal, retroperitoneal or hand assisted the best approach? J Urol 2006;175:1230–4.

6. Gaur DD. Laparoscopic operative retroperitoneoscopy: use of a new device. J Urol 1992;148:1137–9.

Tadashi Matsuda, MD

Ureteroscopy

Shock wave lithotripsy versus ureteroscopy for ureteral calculi: a prospective assessment of patient-reported outcomes. Park J, Shin DW, Chung JH, Lee SW, Department of Urology, Eulji University Hospital, Eulji University College of Medicine, Daejeon, Korea.

World J Urol 2012; Oct. 18 [epub ahead of print].

Objective: To compare patient-reported outcomes (PROs) with objective outcomes after shock wave lithotripsy (SWL) and ureteroscopic surgery (URS) for ureteral calculi (UC).

Methods: We prospectively evaluated 160 consecutive patients who underwent SWL (n=65) or URS (n=95) for a single radiopaque UC ranging from 4 to 15 mm. For patients who underwent URS, a 6-Fr double-J stent was routinely placed for 2 weeks after surgery. To examine PRO, we used a self-administered nonvalidated questionnaire evaluating overall satisfaction and PRO in four domains (pain, hematuria, voiding symptom, and time to return to routine activity) and willingness to undergo the treatment procedure again. Propensity-score matching analysis was performed to adjust for potential confounding by discrepancy of pretreatment parameters between groups. Stone-free rates (SFRs) and complications were also compared.

Results: SFRs after the first, second, and third sessions of SWL were 61.5, 81.0, and 93.5%, respectively. SFR after URS was 100%, which was significantly better than SFRs for third-session SWL (p=0.023). Complications were comparable. By propensity-score matching analysis, overall satisfaction was similar between groups, whereas PRO for voiding symptom and time to return to routine activity were significantly better in the SWL group (all p<0.05). The two groups were not different in willingness to undergo the same procedure again.

Conclusions: Despite significantly higher SFR after URS for UC, overall patient satisfaction was comparable after SWL and URS, meanwhile PRO of the SWL group was better than URS for voiding symptom and time to return to routine activity. In addition of objective treatment outcomes, PROs should be considered in counseling treatment methods for UC.

DOI: 10.1007/s00345-012-0966-2

Commentary

Both ureteroscopy (URS) and shock wave lithotripsy (SWL) are reasonable treatment options for ureteral calculi. Since ureteral calculi are a common clinical scenario, nearly all urologists have firmly held views on the better of the two treatments to offer their patients. Unlike many other urological conditions, the treatment decision often depends on the urologist's opinion rather than objective stone factors or patient preference. The literature is full of studies, meta-analyses, and guidelines that essentially allow urologists to decide for themselves which treatment to offer.

But what about the patient? Thousands of patients have been treated in hundreds of studies. The outcomes measured typically include stone-free rates, length of procedure and hospitalization, and cost. Occasionally a study will report the patient's view, but will only ask them whether they would undergo the same procedure again. Clearly, stone-free rates for ureteral stones should be the primary outcome measure for any study, given that being stone-free must be the goal for this painful condition. Nonetheless, it is remarkable how little has been reported from the patient's point of view.

Park et al report a prospective, non-randomized, comparative study of URS vs. SWL for ureteral calculi using patient-reported outcomes as their primary outcome. They report stone-free rates for the two treatments, which were significantly higher for URS than SWL (even though up to 3 treatments of SWL were allowed). Nonetheless, patient-reported outcomes favored SWL, including voiding symptoms, time to return to routine activity, and visible hematuria. This may in part be due to the fact that URS patients had stents indwelling for 2 weeks.

There are a number of limitations of this study, most notably the lack of randomization. The groups were not comparable in terms of the location of the stone (more commonly upper ureter in the SWL group) or visual pain score (higher in the URS group). Most notably, the questionnaires were not administered at the same time points: URS patients were asked to complete them at the time of stent removal, while SWL patients were asked at a less well-defined point, usually at the time of their third treatment. Perhaps a different outcome would have resulted from giving the URS patients more time to recover.

This study leaves a number of questions unanswered due to these limitations. The upcoming UK randomized trial Therapeutic Interventions for Stones of the Ureter (TISU) comparing URS to SWL will include patient-reported outcomes at various time points. TISU is scheduled to recruit 1000 patients starting this year. Hopefully, it will shed more light on what treatment patients—as opposed to their doctors—prefer.

Francis X. Keeley, MD

The oncologic impact of a delay between diagnosis and radical nephroureterectomy due to diagnostic ureteroscopy in upper urinary tract urothelial carcinomas: results from a large collaborative database. Nison L, Rouprêt M, Bozzini G, Ouzzane A, Audenet F, Pignot G, Ruffion A, Cornu JN, Hurel S, Valeri A, Roumiguie M, Polguer T, Hoarau N, Mérigot de Treigny O, Xylinas E, Matte A, Droupy S, Fais PO, Descazeaud A, Colin P; MD for the French Collaborative National Database on UUT-UC, Department of Urology, Hôpital Claude Huriez, CHRU Lille, Lille, France.

World J Urol 2012; Oct. 16 [epub ahead of print].

Objectives: According to the current upper urinary tract urothelial carcinomas (UTUC) guidelines, ureteroscopic evaluation (URS) is recommended to improve diagnostic accuracy and obtain a grade (by biopsy or cytology). However, URS may delay radical surgery [e.g., nephroureterectomy (RNU)]. The objective of this study was to evaluate the influence of URS implementation before RNU on patient survival.

Methods: A French multicentre retrospective study including 512 patients with nonmetastatic UTUC was conducted between 1995 and 2011. Achievement of ureteroscopy (URS), treatment time (time between imaging diagnosis and RNU), tumour location, pT-pN stage, grade, lymphovascular invasion (LVI) and the presence of invaded surgical margins (R+) were evaluated as prognostic factors for survival using univariate and multivariate Cox regression analyses. Cancer-specific survival (CSS), recurrence-free survival (RFS) and metastasis-free survival (MFS) were calculated using the Kaplan-Meier method.

Results: A total of 170 patients underwent ureteroscopy prior to RNU (URS+group), and 342 did not undergo URS (URS−). The median treatment time was significantly longer in the URS+group (79.5 vs. 44.5 days, p=0.04). Ureteroscopic evaluation was correlated with ureteral location and lower stage and tumour grade (p=0.022, 0.005, 0.03, respectively). Tumour stage, LVI+ and R+ status were independently associated with CSS (p=0.024, 0.049 and 0.006, respectively). The 5-year CSS, RFS and MFS did not differ between the two groups (p=0.23, 0.89 and 0.35, respectively). These results were confirmed for muscle-invasive (MI) UTUC (p=0.21, 0.44 and 0.67 for CSS, RFS and MFS, respectively).

Conclusions: Despite the increased time to radical surgery, diagnostic ureteroscopy can be systematically performed for the appraisal of UTUC to refine the therapeutic strategy without significantly affecting oncological outcomes, even for MI lesions.

DOI: 10.1007/s00345-012-0959-1

Commentary

Diagnostic ureteroscopy for an upper tract abnormality, as opposed to primary nephroureterectomy, remains controversial. Proponents of making a definite diagnosis before extirpative surgery point to the high rate of benign pathological findings in nephroureterectomy series without ureteroscopy. Opponents point to the inevitable delay in carrying out primary nephroureterectomy, which remains the standard of care for upper tract urothelial cancer (UTUC). This study helps address these concerns.

The authors present a large retrospective series of patients undergoing nephroureterectomy, comparing a group of patients who first underwent ureteroscopy to a group who proceeded straight to surgery. Unsurprisingly, they found a significant delay before nephroureterectomy in the ureteroscopy group of 35 days (44.5 vs. 79.5, p=0.04) as well as a much higher proportion of patients who waited over 3 months. Nonetheless, the overall cancer-specific survival, recurrence-free survival, and metastasis-free survival did not differ between the two groups. Unfortunately, the two groups were not well matched in terms of grade, stage, and location of tumor, making firm conclusions difficult to justify.

The fact that the groups were not well matched suggests a selection bias toward diagnostic ureteroscopy in patients with lower stage tumors. The authors do not provide data about the patients who underwent diagnostic ureteroscopy but who did not undergo nephroureterectomy, either because they did not have UTUC or because they were managed endoscopically, nor do we have data on patients undergoing nephroureterectomy who had a benign diagnosis. As a result, we are not given any justification for making a diagnosis before nephroureterectomy. It would be very interesting to see the full picture for all patients presenting with suspected UTUC.

The study addresses an important clinical problem, that of the potential risk of making a definitive diagnosis of UTUC prior to nephroureterectomy. This retrospective study adds to the growing literature on the subject, but does not provide the definitive answer.

Primary nephroureterectomy has not been challenged as the standard treatment of UTUC apart from reports of endoscopic treatment in selected cases. Outcomes for UTUC have not improved for several decades, suggesting that management of this neglected disease needs a radical rethink. Neo-adjuvant chemotherapy has been proposed as a treatment option and does have some justification based on the fact that chemotherapy is less safe for patients with reduced renal function.

The management of UTUC will likely move away from primary extirpative surgery; however, more work is needed to show that a firm diagnosis can be made prior to nephroureterectomy without risking a delay in treatment. This study helps us move closer to the goal of establishing ureteroscopic biopsy as a standard step in the management of UTUC.

Francis X. Keeley, MD

Percutaneous Surgery

Tranexamic acid reduces blood loss in percutaneous nephrolithotomy: a prospective randomized controlled study. Kumar S, Randhawa MS, Ganesamoni R, Singh SK, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

J Urol 2012; Oct. 30 [epub ahead of print].

Purpose: Bleeding is a significant morbidity associated with percutaneous nephrolithotomy (PCNL). This study was conducted to evaluate the safety and efficacy of the anti-fibrinolytic agent tranexamic acid in reducing blood loss in patients undergoing PCNL.

Materials and Methods: A total of 200 patients planned for PCNL were randomized into two equal groups. Patients in tranexamic acid group received one gram of tranexamic acid at induction followed by three oral doses of 500 mg over 24 hours, while those in control group did not receive tranexamic acid. Patient demographics and clinical data of the two groups were compared.

Results: The baseline patient demographics were similar in both the groups. The mean hemoglobin drop in the tranexamic acid was significantly lower than that of the control group (1.39 vs 2.31 g/dL, p<0.0001). Mean operative time in tranexamic acid group was significantly lower than that of control group (48.3 min vs 70.8 min, p<0.0001). Stone clearance rate was similar in both the groups (91% vs 82%, p=0.06). The blood transfusion rate was lower in the tranexamic acid group (2% vs 11%, p=0.018). The complication rate was lower in tranexamic acid group (33% vs 59%, p<0.0001). Two patients with solitary functioning kidney in tranexamic acid group required ureteric stenting to relieve anuria due to clot obstruction.

Conclusions: Use of tranexamic acid in PCNL is safe and is associated with reduced blood loss and lower rate of complications.

Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

DOI: 10.1016/j.juro.2012.10.115

Commentary

Severe hemorrhage is one of the most feared complications of percutaneous nephrolithotomy (PNL) and is associated with complex stone configuration and stone burden. Appropriate access technique, including direct puncture end-on into a calyx, avoidance of infundibular puncture, and using the shortest tract traversing the least amount of parenchyma can help minimize bleeding. Nevertheless, it remains incontrovertible that PNL is accomplished through a controlled stab wound to the kidney, and often multiple stab wounds are required.

In this paper, the authors examined the use of transexamic acid (TA), a safe and inexpensive drug which inhibits plasmin, to decrease bleeding in patients undergoing PNL. A total of 200 patients were randomized, with half receiving intravenous TA immediately before PNL followed by three oral doses over the next 24 hours and half not receiving any drug.

Although not placebo-controlled, the trial was blinded, so the operating surgeon did not know which patients received the drug. The study was adequately powered to detect a five-fold difference in transfusion rate. Prior to the study, the investigators' transfusion rate was 12%, consistent with the 11% of patients in the control group who required a transfusion, while only 2% of patients receiving TA needed blood. Patients in the TA group had shorter operative times, required less intraoperative irrigating fluid, and had lower mean postoperative hemogblobin reduction. Three patients in the control group had severe hemorrhage requiring angioembolization, while none of the TA patients experienced this complication. Stone-free rates were 91% in the TA group vs. 82% in the control group. Patients were generally well-matched in terms of stone burden, number of tracts, site of puncture, and other standard parameters. The authors attributed the improved stone clearance and decrease in operative time in the TA patients to increased visualization that would have resulted from reduction in bleeding. The authors point out that transexamic acid has been shown to be effective in reducing hemorrhage from coronary artery bypass, liver, orthopedic and urologic surgery, including TURP and radical prostatectomy. Moreover, a recent randomized trial of over 20,000 trauma patients showed that TA was associated with a significant reduction in all-cause mortality and death from bleeding.

While technical considerations still remain paramount in preventing severe hemorrhage during PNL, it is comforting to know that pharmacologic therapy might someday make blood transfusion a rarity. Certainly, this agent should be studied at other high volume PNL centers to confirm its efficacy.

Robert Marcovich, MD

Postoperative infection rates in low risk patients undergoing percutaneous nephrolithotomy with and without antibiotic prophylaxis: a matched case control study. Gravas S, Montanari E, Geavlete P, Onal B, Skolarikos A, Pearle M, Sun YH, de la Rosette J, Department of Urology, University Hospital of Larissa, Larissa, Greece.

J Urol 2012;188:843-7.

Purpose: Current guidelines recommend prophylactic antibiotic therapy for all patients undergoing percutaneous nephrolithotomy. We examined the effects of antibiotic prophylaxis in patients undergoing percutaneous nephrolithotomy with negative preoperative urine cultures.

Materials and Methods: Of the 5,803 patients in the CROES (Clinical Research Office of the Endourological Society) Percutaneous Nephrolithotomy Global Study database, a group of 162 patients undergoing percutaneous nephrolithotomy with a negative baseline urine culture who did not receive antibiotic prophylaxis were matched on preoperative nephrostomy, the presence of staghorn calculi and diabetes status with an equal number of patients who received antibiotic prophylaxis. Comparisons were made between the 2 groups in terms of operative and postoperative outcomes, including the incidence of fever and other complications.

Results: Patients who received antibiotic prophylaxis had a lower mean (SD) age at 44.9 (14.2) vs 50.1 (14.4) years (p=0.001). They were also more likely to be in the prone position during the procedure (71.6% vs 39.5%, p<0.001) but less likely to receive postoperative stenting (17.3% vs 32.7%, p=0.002) than those who did not receive prophylaxis. The 2 groups were comparable in terms of all other baseline characteristics and operative factors. Patients who received antibiotic prophylaxis were less likely to experience fever (2.5% vs 7.4%, p=0.040) and other postoperative complications (1.9% vs 22.0%, p<0.0001), and had a higher stone-free rate after percutaneous nephrolithotomy (86.3% vs 74.4%, p=0.006).

Conclusions: Antibiotic prophylaxis of patients undergoing percutaneous nephrolithotomy with a negative baseline urine culture is associated with a significant reduction in the rate of postoperative fever and other complications.

Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

DOI: 10.1016/j.juro.2012.05.007

Commentary

Clinical practice guidelines of the American Urological Association and European Association of Urology recommend antibiotic prophylaxis in all patients undergoing PNL. While this makes sense intuitively, there is not a great deal of data to support this approach. This study was conducted by the Clinical Research Office of the Endourological Society with data culled from its database of 5,803 patients undergoing PNL in centers around the world. Outcomes of 162 patients with negative preoperative urine cultures who did not receive prophylactic antibiotics were compared to those of 162 patients who did receive prophylactic antibiotics, and the two cohorts were matched 1:1 for preoperative presence of nephrostomy tube, staghorn calculi, and diabetes mellitus. The incidence of postoperative fever was found to be three-fold higher in patients who did not receive antibiotic prophylaxis. Unfortunately, due to limitations of the study design, it is unclear what the rates of infection and/or sepsis were in either group. As the authors themselves point out, postoperative fever is not necessarily a sign of infection. The only randomized trial of antibiotic prophylaxis in patients with sterile urine undergoing PNL (reference 11 in the article) was inconclusive due to lack of sufficient sample size (49 patients total). Thus, this article adds only circumstantial evidence to the recommended clinical practice guideline. Until an adequately powered randomized trial is conducted, urologists will continue to have to rely on intuition.

Reference

1. Fourcade RO. Antibiotic prophylaxis with cefotaxime in endoscopic extraction of upper urinary tract stones: a randomized study. The Cefotaxime Cooperative Group. J Antimicrob Chemother 1990;26:77–83.

Robert Marcovich, MD

Extracorporeal Shock Wave

Are there long-term effects of extracorporeal shockwave lithotripsy in paediatric patients? El-Nahas AR, Awad BA, El-Assmy AM, Abou El-Ghar ME, Eraky I, El-Kenawy MR, Sheir KZ, Urology Department, Urology and Nephrology Centre, Mansoura University, Mansoura, Egypt.

BJU Int 2012; Aug. 23 [epub ahead of print].

Study Type - Therapy (outcomes) Level of Evidence 2b What's known on the subject? and What does the study add? Extracorporeal shockwave lithotripsy is effective for the treatment of paediatric renal stones with favourable short-term safety. Extracorporeal shockwave lithotripsy for treatment of paediatric renal stones is also safe for the kidney and the child on long-term follow-up.

Objective: To evaluate the long-term effects of extracoporeal shockwave lithotripsy (SWL) for treatment of renal stones in paediatric patients.

Patients and Methods: Database of paediatric patients who underwent SWL monotherapy for treatment of renal stones from September 1990 through to January 2009 was compiled. This study included only patients with follow-up for more than 2 years. The long-term effects of SWL were evaluated at the last follow-up with measurement of patients' arterial blood pressure, estimation of random blood sugar and urine analysis. The results of diastolic blood pressure were plotted against a standardized age reference curve. The treated kidney was examined by ultrasonography for measurement of renal length and detection of stones. The measured renal lengths were plotted against age-calculated normal renal lengths in healthy individuals.

Results: The study included 70 patients (44 boys (63%) and 26 girls) with mean age at the time of SWL 6.5±3.6 years (range 1–14). The mean follow-up period was 5.2±3.6 years (range 2.1–17.5). The mean age at last follow-up was 11.7±5.3 years (range 4.4–27.5). No patients developed hypertension or diabetes. Only one treated kidney was smaller than one standard deviation of the calculated length. The cause of this was obstruction by a stone in the pelvic ureter 3 years after SWL.

Conclusion: The long-term follow-up after SWL for treatment of renal stones in paediatric patients showed no effect on renal growth and no development of hypertension or diabetes.

© 2012 BJU INTERNATIONAL.

DOI: 10.1111/j.1464-410X.2012.11420.x

Commentary

In this retrospective review, 70 children (mean age 6.5 years) who underwent SWL were followed with arterial blood pressure measurements in addition to renal ultrasound measurements of renal length.¹ After a mean follow-up of 5.2 years, none developed hypertension (diastolic blood pressure [DBP]>95^th percentile]. However, 4 patients had pre-hypertension (DBP>90^th percentile), and thus required follow-up. Except for one kidney, all treated renal units grew according to the growth curves, thus further demonstrating long-term safety of SWL in the pediatric population. The only renal unit that did not grow in this study was that of a chronically obstructed system. This study concurs with the findings of Griffin and colleagues, where 94 children had pre- and 6 months post-SWL DMSA scans.² There were no new scars observed in any of the post-SWL DMSA scans. However, one patient with asymptomatic ureteral obstruction sustained permanent impairment of an SWL-treated renal unit. Thus, in both studies, loss of renal function has been attributed to chronic asymptomatic ureteral obstruction rather than shockwave damage to the kidney. Although pre-hypertension was thought to be related to underlying renal disease rather than effect of shockwaves on renal tissue, future studies need to further define its natural history.

References

1. El-Nahas AR, Awad BA, El-Assmy AM, et al. Are there long-term effects of extracorporeal shockwave lithotripsy in paediatric patients? BJUI 2012; Aug. 23 [epub ahead of print].

2. Griffin SJ, Margaryan M, Archambaud F, et al. Safety of shock wave lithotripsy for treatment of pediatric urolithiasis: 20-year experience. J Urol 2010;183:2332–6.

Sero Andonian, MD

Predictive factors and management of steinstrasse after shock wave lithotripsy in pediatric urolithiasis-a multivariate analysis study. Onal B, Citgez S, Tansu N, Demirdag C, Dogan C, Gonul B, Demirkesen O, Obek C, Erozenci A, Department of Urology, University of Istanbul Cerrahpasa Medical Faculty, Istanbul, Turkey.

Urology 2012;80:1127-31.

Objective: To define the predictive factors for the formation of steinstrasse (SS) after shock wave lithotripsy (SWL) and determine the treatment strategies for this complication in pediatric urolithiasis.

Methods: We retrospectively reviewed the data of 341 renal units (RUs) treated with SWL for urolithiasis. The stone location, stone burden, auxiliary procedures, energy level, and number of shock waves were recorded. Statistical analysis was performed to detect the predictive factors for the formation of SS. In addition, the treatment of children with SS was evaluated.

Results: The mean age of the children was 8.31 years (range 1–17). Episodes of SS developed in 26 RUs (7.6%). Of the 26 RUs, 20 (77%) were localized in the lower, 5 (19%) in the upper, and 1 (4%) in multiple locations in the ureter. The stone burden was the only statistically significant factor predicting the formation of SS on logistic regression analysis (P=.001). Of the 26 RUs, 17 (65.4%) were successfully managed by repeat SWL monotherapy, 4 (15.4%) were managed with ureteroscopy after failure of SWL, 1 (3.8%) was managed by ureteroscopy monotherapy, and 4 (15.4%) were monitored with conservative management with antispasmodic drug plus hydration therapy. The mean number of SWL sessions was 1.72.

Conclusion: The incidence of SS development in children after SWL treatment was similar to that in adult series. Our results suggest that the stone burden is a significant predictive factor for the development of SS after SWL in pediatric urolithiasis. Most children with SS could be easily and safely treated by repeat SWL.

Copyright © 2012 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.urology.2012.06.043

Commentary

Although children are thought to pass ureteral stone fragments more efficiently than their adult counterparts due to their shorter and more elastic ureters, the rate of steinstrasse (SS) development in 341 pediatric renal units treated with SWL was found to be 7.6%, similar to adults.¹ On multivariate analysis, stone area was the only significant factor, with SS rates of 1.9% for stones <1cm², 15.4% for stones 1-2cm², and 19.5% for stones >2cm². While most were treated successfully with repeat SWL, 15.4% were managed conservatively with antispasmodics and hydration. Surprisingly, 19% of stone fragments impacted the proximal ureter, while the majority (77%) forming SS in the usual distal ureteral location. Since tamsulosin has been shown in RCTs to be effective in children with distal ureteral stones (dose of 0.4mg in children >4yrs old and 0.2mg in younger children),² it could be offered off-label to children at risk of developing SS post-SWL (those with stone burden >2cm²). RCTs randomizing pediatric patients undergoing SWL to tamsulosin vs. placebo are needed and would be feasible in large-volume pediatric centers.

References

1. Onal B, Citgez S, Tansu N, et al. Predictive factors and management of steinstrasse after shock wave lithotripsy in pediatric urolithiasis- a multivariate analysis study. Urology 2012;80:1127–31.

2. Mokhless I, Zahran AR, Youssif M, et al. Tamsulosin for the management of distal ureteral stones in children: a prospective randomized study. J Pediatr Urol 2012;8:544–8.

Sero Andonian, MD

Transurethral Procedures

Population based trends in the surgical treatment of benign prostatic hyperplasia. Schroeck FR, Hollingsworth JM, Kaufman SR, Hollenbeck BK, Wei JT, Division of Health Services Research, Department of Urology, University of Michigan, Ann Arbor, MI.

J Urol 2012;188:1837-41.

Purpose: Laser prostatectomy has increased in popularity in the last decade. However, traditional transurethral resection of the prostate remains common. To understand decisions about the use of laser prostatectomy vs transurethral prostate resection, we evaluated trends in transurethral surgery for benign prostatic hyperplasia in an all payer data set, focusing on patient and provider factors associated with the receipt of laser prostatectomy.

Materials and Methods: Using Florida State Inpatient Database and Ambulatory Surgery Database, we identified patients who underwent laser prostatectomy or transurethral prostate resection from 2001 to 2009. We calculated surgery rates with time, stratified by procedure type. We used multilevel regression to examine patient (age, race and comorbidity level) and provider (surgeon volume) factors associated with the receipt of laser prostatectomy vs transurethral prostate resection.

Results: While the overall rates of transurethral surgery remained stable during the study period (p=0.227), laser prostatectomy use increased 400% from 25 to 114 procedures per 100,000 men (p<0.001), replacing about half of all transurethral prostate resections. Patients were less likely to undergo laser prostatectomy if they were older (OR 0.65, 95% CI 0.61-0.70) and less healthy (OR 0.48, 95% CI 0.45-0.51). While these factors were predictive of surgery type, most of the variation in laser prostatectomy use (69%) was determined by the urologist seen by the patient.

Conclusions: Laser prostatectomy use has increased in the last decade at the expense of transurethral prostate resection, driven largely by provider effects. However, elderly and more infirm patients are least likely to undergo it, raising concern about underuse in this population.

Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

DOI: 10.1016/j.juro.2012.07.049

Commentary

This study by Schroeck et al confirms the rise in popularity of laser prostatectomy in the U.S., with 50% of transurethral BPH treatments in Florida in 2009 being laser-based compared with less than 10% in 2001. This rise was in the face of stable overall transurethral surgery rates at 230-250/100,000 men over this same time period. Interestingly and perhaps unsurprisingly, most (69%) of the “variation in receipt of laser prostatectomy” was explained by the surgeon rather than by patient factors.¹ There were 3,156 surgeons in the models and it was felt that “physician practice styles” or other unmeasured physician factors were the main driver of the move to laser prostatectomy over the period studied. There was no ability to determine what laser procedure or type of TURP equipment was employed in this study because of the less-specific ICD-9-CM codes employed. Office-based procedures such as needle ablation or thermotherapy were not captured, however.

As the cost of BPH treatments in the U.S. annually exceeds $3 billion, the need for demographic data of this type is obvious. The laser prostatectomy business is driven and largely governed by the market for expensive disposable items—laser fibers. In this fact, not all laser prostatectomy procedures are created equal. The various vaporization procedures typically require 1-3 single-use fibers per case and hence can be quite costly, whereas holmium enucleation utilizes reusable fibers which are not only cheaper but can be reused many times with significant cost savings. Cost-effectiveness studies performed with sound, unbiased methodology weighing the different strengths and weaknesses of each laser technique are not available but will become important as electrocautery for resection, vaporization and enucleation makes a comeback.

How individual surgeons choose the transurethral treatments that they offer is another matter entirely. Clearly it has little to do with patient factors as evidenced by these studies, so it likely involves a host of surgeon factors such as company marketing, reimbursement, public profile, ease-of-use, “gadget/gizmo idolatry,” peer pressure, perceived if not actual patient advantages and many others. Blood loss is the single most tangible advantage of laser prostatectomy compared to TURP, but with the rise of ‘”super-powered” lasers (>120 W) and the laser “arms race,” this advantage appears to be diminishing as they appear to be less hemostatic and new problems with devitalized residual tissue are emerging. It will be interesting to see whether or not the trends associated with thermal energy-based treatments seen in this article will continue or whether technique-based or non-thermal technologies will emerge in the next decade.

Reference

1. Schroeck FR, Hollingsworth JM, Kaufman SR et al. Introduction of laser technology and procedure use for benign prostatic hyperplasia: data from Florida. Urology 2012;80:678–83.

Peter Gilling, MD

Urodynamic effects of transrectal intraprostatic Ona botulinum toxin A injections for symptomatic benign prostatic hyperplasia. de Kort LM, Kok ET, Jonges TN, Rosier PF, Bosch JL, Department of Urology, University Medical Center Utrecht, Utrecht, the Netherlands.

Urology 2012;80:889-93.

Objective: To investigate urodynamic, symptomatic, and histologic effects of intraprostatic injection with Ona botulinum toxin A for benign prostatic hyperplasia.

Methods: Patients >55 years with symptomatic benign prostatic hyperplasia failing medical therapy were treated. Inclusion criteria were International Prostate Symptom Score >7, prostate volume 30-50 cm³, and urodynamic bladder outlet obstruction>Schäfer grade 2. A transrectal intraprostatic injection of 200 IU Ona botulinum toxin A was given. Filling cystometry and pressure flow studies were performed at 3, 6, and 12 months post injection. International Prostate Symptom Score, International Prostate Symptom Score quality of life, prostate-specific antigen, and prostate volume were measured up until 12 months; prostate biopsies before and after Ona botulinum toxin A injection were done for histology and cell proliferation.

Results: Fifteen men (mean age 64.9 years) were included. Ona botulinum toxin A injection was well tolerated with few complications. Postvoid residual improved (170 to 80 mL), but maximum flow rate and bladder outlet resistance parameters did not change during follow-up. International Prostate Symptom Score and International Prostate Symptom Score quality of life improved (22 to 13 and 5 to 2, respectively), whereas prostate-specific antigen and prostate volume remained unaltered. Cell proliferation did not decrease and in 37% and 64% of pre- and posttreatment biopsies, respectively, some degree of prostatitis was found. Ten of 15 patients eventually underwent transurethral prostate resection because of persisting symptoms.

Conclusion: Intraprostatic Ona botulinum toxin A for symptomatic benign prostatic hyperplasia did not affect urodynamic outcomes, except for postvoid residual. Although symptom scores improved, we were not able to show change in prostate volume, prostate-specific antigen, or histologic outcomes. A placebo effect of intraprostatic Ona botulinum toxin A could not be ruled out.

Copyright © 2012 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.urology.2012.06.004

Commentary

Over the past 10 years Ona botulinum toxin A has been investigated as an intra-prostatic injection for the treatment of symptomatic BPH with less-than-spectacular results. This neurotoxin inhibits release of various neurotransmitters including acetylcholine in sympathetic, parasympathetic and sensory nerves with resultant inhibition of cell proliferation and apoptosis in rat models. The hope was that prostatic involution and shrinkage would occur, relieving bladder outflow obstruction and reducing lower urinary tract symptoms.¹ In many cases however, a reduction in symptoms was noted in the absence of a change in prostate volume.²

This study by de Kort et al looks in detail at the urodynamic effects of Botox in a group of men with symptomatic BPH. 100 IU was injected as a single trans-rectal injection into each lobe of the prostate. A full urodynamic evaluation was done before treatment and at 3, 6 and 12 months afterward, trans-rectal ultrasound volumes were done at 1, 6 and 12 months, and, interestingly, biopsies were done 1 month before and 1 month after injection.

The findings were instructive. Of 15 patients studied, 11 ultimately required TURP (1 acute retention and 10 with persistent symptoms). Despite this, there was actually a significant and sustained fall in IPSS score, from 22 beforehand to 13 at 12 months, and the IPSS-QOL fell from a mean of 5 to 2 over the same period. These were the only positive findings, however, with no significant change being noted in these patients in any of the other parameters measured apart from post-void residual. No change was seen in Qmax, PdetQmax, Schäfer grade, prostate volume or PSA level. The biopsies did not show a significant change in PCNA-positive cells, which the authors had used as a proxy for cellular proliferation.

In the Comments section of this paper, the authors conceded that the change in symptoms noted was entirely consistent with a placebo effect, which is typically around a 20% reduction in BPH studies, and they felt that the use of intra-prostatic Botox injections should probably be limited to placebo-controlled trials! Interestingly, the 9-point fall in IPSS symptom score noted in this study was identical to that found with intra-prostatic injection of PRX-302 where a placebo arm was employed.³ Whether injection therapy will ever be anything more than a side-show for the treatment of BPH still remains to be seen.

References

1. Kuo HC. Prostate botulinum A toxin injection–an alternative treatment for benign prostatic obstruction in poor surgical candidates. Urology 2005;65:670–4.

2. Chuang YC, Chiang PH, Huang CC et al. Botulinum toxin type A improves benign prostatic hyperplasia symptoms in patients with small prostates. Urology 2005;66:775–9.

3. Elhilali MM, Pommerville P, Yocum RC et al. Prospective, randomized, double-blind, vehicle-controlled, multicenter phase IIb clinical trial of the pore-forming protein PRX302 for targeted treatment of symptomatic benign prostatic hyperplasia. J Urol 2012; Nov. 7 [epub ahead of print].

Peter Gilling, MD

Medical Aspects of Endourology

From hypercalciuria to hypocitraturia-a shifting trend in pediatric urolithiasis? Kovacevic L, Wolfe-Christensen C, Edwards L, Sadaps M, Lakshmanan Y. Department of Pediatric Urology, Children's Hospital of Michigan, Detroit, MI.

J Urol 2012;188(4 Suppl):1623-7.

Purpose: We analyzed the metabolic abnormalities in children with urolithiasis, and the relationship between diet and hypocitraturia.

Materials and Methods: A single center, retrospective analysis was conducted in all children with renal and/or ureteral calculi seen at our Multidisciplinary Stone Clinic between January 2010 and July 2011. Data at presentation were extracted from the clinical database.

Results: We analyzed 63 children (37 girls) with urolithiasis with a mean age of 13.43±4.61 years. Of the 45 patients with 24-hour urinalysis, a metabolic risk factor was present in 68.9%, with hypocitraturia (58.1%) and hypercalciuria (48.3%) being the most common. Children with isolated hypocitraturia had lower urinary magnesium and potassium levels (1.06±0.62 mg/kg and 0.53±0.24 mmol/kg per day) than those with no metabolic abnormalities (1.72±0.61 mg/kg and 0.68±0.20 mmol/kg per day) (p=0.015 and p=0.132, respectively). Urinary citrate was positively correlated with urinary potassium (r=0.50, p=0.002) and urinary magnesium (r=0.49, p=0.001). Dietary analysis revealed a lower intake of magnesium and potassium in children with hypocitraturia (28.97%±12.25% and 15.42%±7.25% recommended dietary index) than in normocitraturic cases (51.06%±17.51% and 45.23%±29.49% recommended dietary index) (p=0.042 and p=0.056, respectively).

Conclusions: The majority of children had an identifiable metabolic risk factor for urolithiasis, with hypocitraturia being the most common. This shift in metabolic trend may be a significant contributor to the increasing incidence in pediatric urolithiasis. Hypocitraturia appears to be dietary in origin, correlated with a low consumption of potassium and magnesium.

Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

DOI: 10.1016/j.juro.2012.02.2562

Commentary

In this interesting report the authors address the problem of increased incidence of urolithiasis in childhood. In a group comprising 70 children with stones, 24h urine collections were obtained in 45. One or several biochemical abnormalities were identified in 31 of these children (69%). The bottom line of the report is that hypocitraturia and hypercalciuria were the dominating risk-factors in 58% and 48% of the children, respectively. Inasmuch as a relationship also was demonstrated between urinary citrate and potassium as well as between citrate and magnesium, an insufficient dietary supply of potassium and magnesium was suggested as an explanation of the reduced excretion of citrate. Unfortunately, the authors did not include pH in their measurements, but it can be assumed that the low potassium excretion was associated with an increased excretion of hydrogen ions. Moreover, a reduced urinary citrate accompanies a reduced urinary pH.

The role of magnesium is interesting. Not only was the magnesium excretion significantly lower in children with hypocitraturia, but the food content of magnesium (as well as that of potassium) was significantly lower.

Although the authors conclude that there has been a shift over time from hypercalciuria to hypocitraturia, the former risk factor is still common. Additionally, it can be suspected that during recent years, there has been an increased interest in urinary citrate and also improved methods for citrate analysis.

It is highly likely that the low pH explains hypocitraturia and also causes an increased dissociation of citrate. The inhibiting properties of citrate in terms of calcium oxalate as well as calcium phosphate crystal growth and aggregation thereby are reduced. For that reason and with a simultaneously increased production of OPN and polymerization of Tamm-Horsfall protein, there will be a facilitated nucleation and growth of calcium oxalate in relation to Randall's plaques.^1,2 The low magnesium excretion is notable because magnesium in addition to a reduced inhibition of calcium oxalate crystal formation the growth of calcium phosphate also is reduced. This effect is thus enforced by the simultaneously low urinary citrate.

It is notable that the authors found the largest stones in the hypocitraturic children. This is possibly a reflection of a rapid growth of stones fixed to the papillae.

The findings presented in this report strongly support the crucial role of a low urine pH for development of calcium oxalate stones.^2,3 The lesson learned is that, in addition to the need to carefully improve the dietary intake of potassium and magnesium, when pharmacological treatment is indicated a combination of potassium citrate and magnesium seems most appropriate. This regimen will increase urine pH, citrate and magnesium and is, moreover, associated with no or minor side effects and accordingly particularly suitable for children.

References

1. Coe FL, Evan AP, Worcester EM et al. Three pathways for human kidney stone formation. Urol Res 2010;38:1471–60.

2. Tiselius HG, Lindbäck B, Fornander AM et al. Studies on the role of calcium phosphate in the process of calcium oxalate crystal formation. Urol Res 2009;34:181–92.

3. Tiselius HG. A hypothesis of calcium stone formation: an interpretation of stone research during the past decades. Urol Res 2011;39:231–43.

Hans-Göran Tiselius, MD

Increased water intake as a prevention strategy for recurrence of urolithiasis: major impact of compliance on cost-effectiveness. Lotan Y, Jiménez IB, Lenoir-Wijnkoop I, Daudon M, Molinier L, Tack I, Nuijten MJ, Department of Urology, The University of Texas Southwestern Medical Center at Dallas, TX.

J Urol 2012; Sep. 24 [epub ahead of print].

Purpose: Evaluate economic impact of preventing recurrent stones using strategy of increased water intake and determine the impact of compliance on cost-effectiveness for French health care system.

Materials and Method: Markov model was constructed to compare costs and outcomes for recurrent kidney stone formers with <2 liters/day vs. ≥2 liters/day fluid intake. Model assumptions included: annual prevalence of 120,000 stone episodes in France; 14.4% annual risk of stone recurrence; and 55% risk reduction in subjects with adequate water intake. Costs were based on resource utilization as estimated by panel of experts and official national price lists. Outcomes were from perspective of public health payer and encompassed both direct and indirect costs.

Results: Total cost of episode of urolithiasis was estimated at €4,267 including cost of treatment and complications. This corresponds to an annual budget impact of 88 million for recurrent stones based on 21,000 stone events. Assuming 100% compliance with fluid intake recommendations of 2 liters/day, 11,572 new stones might be prevented, resulting in €49 million cost savings. Compliance with water intake in only 25% of patients would still result in 2,893 fewer stones with cost saving of €10 million. Varying cost of managing stones had smaller impact on outcomes since many patients do not make stones. Varying incidence of complications did not change the incidence of stones and had negligible effect on overall cost.

Conclusions: Preventing recurrent urolithiasis has a significant cost saving potential for a payer as a consequence of reduced stone burden. However, compliance is an important factor in determining cost-effectiveness.

Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

DOI: 10.1016/j.juro.2012.08.254

Commentary

The important matter highlighted in this article is how recurrence prevention can reduce the cost associated with stone formation. Stone patients represent a large group in need of medical care and the cost is caused by emergency procedures, elective active stone removal and absence from work, as well as indirect costs associated with any kind of stone treatment. In this regard both the high prevalence and the high rate of recurrence play a role. It is obvious that an appropriate choice of procedures for taking care of the stone problem, whether conservative or surgical, together with effective recurrence prevention is both desirable and necessary to reduce the total economic burden on the health care system.

In this report the importance of sufficient fluid (water) intake for recurrence prevention is addressed and the advantage of drinking more than 2 litres a day is discussed in terms of compliance. It is well recognised that compliance of pharmacological treatment is low; usually not more than 50-60%.¹ The long-term patient compliance to dietary and drinking advice is probably much lower, but there is a lack of literature data supporting that assumption.

A discussion is presented about how compliance with a high water intake can be improved. This is an important aspect in that, as compared to other alternatives, water intake certainly is the least expensive regimen with the lowest risk of side effects. Several suggestions are put forward. The use of dip-stick testing to decide how efficient the regimen is in diluting urine is one alternative that is mentioned. This is probably the best way to proceed in order to maintain the interest of the patient. In this regard it might be of interest to remind readers of the Urimho™ device that was developed in order to measure conductivity in only drips of urine.² This approach was, unfortunately, too expensive and it is my understanding that this device is no longer available. Nevertheless, the idea was brilliant and it would indeed be great to have a similar device that not only measures urine dilution but also urine pH, the latter another very important determinant of stone formation.

The article discussed here does not give any data on the level of compliance, but it is probably correctly assumed that it is low and that it decreases over time. Therefore a simple and not too expensive device for the patient to measure the potential risk of stone formation would probably be the best reminder to get an improved compliance irrespective of whether drinking, dietary, or pharmacological treatment is used to prevent recurrent stone formation.

References

1. Tiselius HG, Advisory Board of European Urolithiasis Research and EAU Health Care Office Working Party for Lithiasis. Possibilities for preventing recurrent calcium stone formation: principles for the metabolic evaluation of patients with calcium stone disease. BJU Int 2001;88:158–68.

2. Tiselius, HG. Calcium oxalate crystallization properties in urine with different specific electrical conductivities. J Urol 1992;148: 990–4.

Hans-Göran Tiselius, MD

Investigative Endourology

Urinary stone risk and cola consumption. Herrel L, Pattaras J, Solomon T, Ogan K, Department of Urology and General Clinical Research Center, Emory University School of Medicine, Atlanta, GA.

Urology 2012;80:990-4.

Objective: To evaluate the effect of cola consumption on urinary stone risk factors in a controlled metabolic environment with a prospective cross-over study.

Methods: Thirteen participants (10 normal and 3 calcium oxalate stone-formers) underwent 2 6-day phases on a controlled metabolic diet. During phase 1, subjects ingested 1 liter of cola daily, followed by a 3-week washout period. During phase 2, subjects ingested 1 liter of deionized water daily. Twenty-four-hour urine collections and serum metabolic panels were obtained for stone risk factors at the end of each phase. Urine and serum results of the cola phase were compared with those of the water phase.

Result: Normal subjects and stone-formers were combined for analysis after determining no significant difference between the 2 groups. No significant differences were found among cola and water treatment groups for normal subjects, stone-formers, or the pooled group.

Conclusion: Cola exerts no detectable change in urinary risk factors associated with calcium oxalate stone formation. Cola consumption may not increase stone risk and may be an acceptable alternative source of daily fluid for patients unwilling to increase water consumption.

Copyright © 2012 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.urology.2012.07.003

Commentary

A high fluid intake is one of the most important cornerstones of kidney stone dietary prevention. A sufficiently dilute urine will prevent the individual chemical components of stones from becoming concentrated enough to precipitate out of solution. Until this study, the majority of patient advice leaflets discouraged the use of cola to increase fluid intake. Indeed, the NIDDK website specifically states “Grapefruit juice and dark colas have been found to increase the risk of stone formation and should be avoided by people who are prone to calcium oxalate stone formation.”¹

This small study has shown that cola exerts no detectable change in urinary risk factors associated with the commonest type of stone. In some cases, it may make life easier for that cohort of our patients who prefer cola drinks.

Reference

1. National Institute of Diabetes and Digestive and Kidney Diseases. Diet for Kidney Stone Prevention. http://kidney.niddk.nih.gov/kudiseases/pubs/kidneystonediet/index.aspx. Accessed November 6, 2012.

Abhay Rane, MS

Residual fragments following ureteroscopic lithotripsy: incidence and predictors on postoperative computerized tomography. Rippel CA, Nikkel L, Lin YK, Danawala Z, Olorunnisomo V, Youssef RF, Pearle MS, Lotan Y, Raman JD, Division of Urology, Penn State Milton S. Hershey Medical Center, Hershey, PA.

J Urol 2012; Oct. 18 [epub ahead of print].

Purpose: Residual fragments following ureteroscopy for calculi may contribute to stone growth, symptoms or additional interventions. We reviewed our experience with ureteroscopy for calculus disease to define the incidence and establish factors predictive of residual fragments.

Materials and Methods: Records associated with 667 consecutive ureteroscopic lithotripsy procedures for upper urinary calculi were reviewed. In 265 procedures (40%) computerized tomography was done between 30 and 90 days postoperatively. They comprised the study group. Residual fragments were defined as any residual ipsilateral stone greater than 2 mm.

Results: Included in the study were 121 men and 127 women with a mean age of 47 years. Mean target stone diameter was 7.6 mm. The stone location was the kidney in 30% of cases, ureter in 50%, and kidney and ureter in 20%. Residual fragments were detected on computerized tomography after 101 of 265 procedures (38%). Pretreatment stone size was associated with residual fragments at a rate of 24%, 40% and 58% for stones 5 or less, 6 to 10 and greater than 10 mm, respectively (p<0.001). Additionally, stone location in the kidney (p<0.001) or the kidney and ureter (p=0.044), multiple calculi (p=0.003), longer operative time (p=0.008) and exclusive use of flexible ureteroscopy (p=0.029) were associated with residual fragments. In a multivariate model only pretreatment stone diameter greater than 5 mm was independently associated with residual fragments after ureteroscopy (diameter 6 to 10 and greater than 10 mm OR 2.03, p=0.03 and OR 3.74, p=0.003, respectively).

Conclusions: Of patients who underwent ureteroscopic lithotripsy for calculi 38% had residual fragments by computerized tomography criteria, including more than 50% with stones 1 cm or greater. Such data may guide expectations regarding the success of ureteroscopy in attaining stone-free status.

Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

DOI: 10.1016/j.juro.2012.08.040

Commentary

Patients expect to be given a predictive success rate for any procedure, however simple or complex it might be. Ureterorenoscopic lithotripsy (URSL) may be a challenging procedure, especially in the upper urinary tract. The goal of URSL is to fragment stones, actively basket and remove most fragments and allow the remaining fragments to pass spontaneously. The reality is that smaller fragments may be difficult to extract or may be missed. This report helps gives clinicians some data regarding expected stone-free status following URSL in a variety of locations, which can help guide patient expectation.

Abhay Rane, MS

ROBOTICS

Costs of radical prostatectomy for prostate cancer: a systematic review. Bolenz C, Freedland SJ, Hollenbeck BK, Lotan Y, Lowrance WT, Nelson JB, Hu JC, Department of Urology, Mannheim Medical Center, University of Heidelberg, Mannheim, Germany.

Eur Urol 2012; Sep. 5 [epub ahead of print].

Context: Robot-assisted laparoscopic radical prostatectomy (RALP) has been rapidly adopted as a new approach for radical prostatectomy (RP) in patients with prostate cancer (PCa). The use of new technology may increase costs for RP.

Objective: To summarize data on direct costs of various approaches to RP and to discuss the consequences of cost differences.

Evidence Acquisition: A systematic literature search was performed in March 2012 using the PubMed, Web of Science, and Cochrane Library databases. A complex search strategy was applied. Articles were selected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Articles reporting on direct costs of RP (open retropubic [RRP], radical perineal [RPP], laparoscopic [LRP], RALP) in men with clinically localized PCa were eligible for study inclusion.

Evidence Systhesis: Of 1218 articles initially screened by title, the multistep, systematic search identified 11 studies presenting direct costs of different approaches to RP. Of the 11 studies, 7 compared the costs of different RP approaches. Minimally invasive RP (MIRP) (ie, LRP or RALP) was more expensive than RRP in most studies, mainly due to increased surgical instrumentation costs. In the comparative studies, costs ranged from (in US dollars) $5058 to $11806 for MIRP and from $4075 to $6296 for RRP, with RALP having the highest direct costs. In one study applying standardized, health economic-evaluation criteria, RALP was not found to be cost effective. Limitations of this review include significant differences in observational study designs and an absence of prospective comparative studies. Moreover, there are limited post-RP data on the costs of adjuvant treatments and other health care-related expenses after PCa surgery.

Conclusions: Few studies compared direct costs of different approaches to RP. The use of new technology, particularly RALP, results in added costs for the procedure. Cost effectiveness of new technologies should be assessed before widespread adoption. To date, in the lone study to evaluate this, RALP was not found to be cost effective from a health care, economic standpoint. However, longer follow-up of patients is required to better evaluate its impact on overall costs and quality of PCa care.

Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

DOI: 10.1016/j.eururo.2012.08.059

Commentary

This thorough study examines the literature to help define the current status of cost comparison issues between open radical prostatectomy and robot-assisted radical prostatectomy. A very intelligent and logical analysis is presented defining this topic. Undoubtedly, robot-assisted surgery will cost more in relation to the direct material costs. This is not a point of debate, whether one is a robotic surgery advocate or detractor. However, the authors' slant in the article seems to be along the negative side toward robotics and the picture is painted that the data available suggests that this additional cost is likely not worth the benefit. The authors cite a paucity of data of clinical benefits of robot prostatectomy despite the wealth of data that has been recently published and continues to grow in a rather lopsided fashion in favor of robot prostatectomy outcomes.

However, let us make the assumption that robotic surgery is better but only to a small degree. Let us say that only a few more patients will have a cardiac event or a deep vein thrombosis while undergoing an open radical prostatectomy as opposed to robot prostatectomy. Perhaps we must at some point make this leap as a society of providing a slightly inferior procedure because it costs less. Certainly lines must be drawn at some level. However, if I as a surgeon can perform a minimally invasive type of case very well with the personal experience that this option is safer for my patient then I would still opt to perform this procedure even if it is a bit more expensive. At this point in the development of robot prostatectomy I seriously doubt whether this technology will ever be “revoked” from a governmental standpoint where it has become so well entrenched as the preferred treatment option in most centers over radical prostatectomy. But the point is well taken that any future technologies that might be more costly should be placed under great scrutiny in order determine whether the benefits outweigh the costs and robotic surgery can act as a historical model regarding how the process might have been improved. As far as robotic surgery goes however, that train left the station quite a while ago.

David Lee, MD

THERMAL/ABLATIVE TECHNOLOGY

Focal salvage therapy for localized prostate cancer recurrence after external beam radiotherapy: a pilot study. Ahmed HU, Cathcart P, McCartan N, Kirkham A, Allen C, Freeman A, Emberton M, Division of Surgery and Interventional Science, University College London, London, United Kingdom.

Cancer 2012;118:4148-55.

Background: The objective of this study was to evaluate the safety, feasibility, side-effect profile, and proof of concept for focal salvage therapy using high-intensity focused ultrasound (HIFU).

Methods: A registry-based analysis was conducted between 2004 and 2009 of 430 patients who underwent HIFU. Thirty-nine patients received focal salvage therapy for localized recurrence after external beam radiotherapy. Multiparametric magnetic resonance imaging studies combined with transperineal template prostate mapping biopsies or transrectal biopsies were used to localize disease. Validated questionnaires were used to assess functional outcomes. Biochemical failure was defined by using both Phoenix criteria (prostate-specific antigen [PSA] nadir plus 2 ng/mL) and Stuttgart criteria (PSA nadir plus 1.2 ng/mL).

Results: The mean pre-HIFU PSA level was 4.6 ng/mL. The median follow-up was 17 months (interquartile range, 10–29 months). International Index of Erectile Function-5 scores decreased from a median±standard deviation (SD) of 18±16 to 13±21 at 6 months, demonstrating worsening function. Scores on the University of California Los Angeles-Expanded Prostate Cancer Index Composite Urinary domain indicate that pad-free, leak-free continence status was 64%, and the pad-free rate was 87.2% at last follow-up. One rectourethral fistula occurred and spontaneously resolved with urinary and bowel diversion. The actuarial progression-free survival rate (including PSA nonresponders) was 69% at 1 year and 49% at 2 years according to Phoenix criteria. Excluding PSA nonresponders, these rates were 74% and 58%, respectively (Phoenix criteria).

Conclusions: The results from this study indicated that focal salvage therapy is a potential strategy for localized recurrence after radiotherapy that may reduce the harms resulting from whole-gland salvage therapies.

Copyright © 2011 American Cancer Society.

DOI: 10.1002/cncr.27394

Commentary

This prospective trial of salvage HIFU for local recurrent prostate cancer after EBRT included 39 patients with median pre-PSA of 3.3 ng/ml and median 17 months' follow-up. At entry, all men had 1.5T multi-parametric MRI studies in combination with either transperineal 5-mm grid template prostate mapping (TPM) biopsies or TRUS biopsies. The former group underwent lesion-targeted focal therapy (with a margin of normal tissue) for the recurrent MR-visible cancer proven by TPM biopsy, which corresponded with the site of the index lesion before EBRT, and the later group underwent hemiablation. In the outcome, median PSA nadir of 0.57 ng/ml (range 0.1–2.3) was achieved at mean time to nadir of 4.3 months. Unfortunately, only 9 men (9/39, 23%) had postoperative surveillance biopsy, in which 4 (4/9, 44%) were positive for cancer (4/39, 10%). The postoperative pad-free rate was 87% at last follow-up, and IIEF-15 changed from 18 (pre) to 14 (post-6 months). No TURP were done at salvage HIFU, and 83% had successful trial of void at first attempt. The authors divided the cohort into 2 groups: (a) those who achieved a PSA nadir <0.5ng/ml (17/39, 44%), and (b) those who did not (22/39, 56%). The 1-year, 2-year, and 3-year biochemical-free survival rates of Group (a) vs. Group (b) using Phoenix criteria (PSA nadir plus 2 ng/ml) were 86% vs. 55%, 75% vs. 67%, and 63% vs. 45%, respectively. The authors discuss the localization of disease within the gland as being key to facilitating focal salvage therapy, especially using TPM or MRI.

This study suggested that focal salvage therapy using HIFU may be an option in selected patients, and that the complication by focal salvage therapy clearly appears lower than that of whole-gland ablation therapy. Although challenges in three-dimensional localization of cancer remain, the cancer mapping technique with integrated use of imaging and targeted biopsy is now increasingly gaining interest.^1,2 Importantly, this paper also suggests that the role of postoperative PSA after focal therapy is generally supposed to become less; however, PSA nadir or percent decrease of PSA from pre- to post-focal therapy still seems important for predicting the successful ablation of the index lesion by focal therapy.¹ Further assessments of the role of postoperative biomarkers, including PSA, as well as the role of postoperative surveillance biopsy are necessary for establishing a reliable monitoring modality after focal therapy.

References

1. Bahn D, de Castro Abreu AL, Gill IS et al. Focal cryotherapy for clinically unilateral, low-intermediate risk prostate cancer in 73 men with a median follow-up of 3.7 years. Eur Urol 2012;62:55–63.

2. Moore CM, Robertson NL, Arsanious N et al. Image-guided prostate biopsy using magnetic resonance imaging-derived targets: a systematic review. Eur Urol 2013;63:125–40.

Osamu Ukimura, MD, PhD