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RIRS in the elderly: Is it feasible and safe?
International Journal of Surgery 42 (2017) 147e151
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International Journal of Surgery journal homepage: www.journal-surgery.net
Original Research
RIRS in the elderly: Is it feasible and safe? F. Berardinelli, MD, FEBU a, *, P. De Francesco a, M. Marchioni a, N. Cera b, S. Proietti c, D. Hennessey d, O. Dalpiaz e, C. Cracco f, C. Scoffone f, G. Giusti c, L. Cindolo a, L. Schips a a
Department of Urology, “S. Pio da Pietrelcina’’ Hospital, Vasto, CH, Italy Faculty of Psychology and Educational Sciences, University of Porto, Porto, Portugal c Urology Dept, Urological Research Institute, IRCCS Ospedale San Raffaele, Ville Turro Division, Milan, Italy d Department of Urology, Austin Health, Melbourne, Australia e €t, Graz, Austria Urologische Klinik, Medizinische Universita f Urologia, Ospedale Cottolengo, Torino, Italy b
h i g h l i g h t s RIRS has gain more acceptance as first line therapy in renal stones up to 2 cm. RIRS is an effective and safe technique regardless the age of patients. RIRS is a surgical technique with a low complication rate.
a r t i c l e i n f o
a b s t r a c t
Article history: Received 26 April 2017 Accepted 27 April 2017 Available online 3 May 2017
Background: The aim of this study was to compare the safety and efficacy of RIRS in men 65 years to those <65 years. Materials and methods: Patients who underwent RIRS were prospectively collected from March 2013 to March 2014 in 5 European centers. Perioperative outcomes and complications in elderly men were compared with men <65 years. Univariable and multivariable analyses were performed for factors predicting overall complications. The groups were compared using ManneWhitney U test. Categorical variables were compared using chi-squared test and the Yates correction or the Fisher's exact test. Results: A total of 399 patients with renal stones were included, 308 (77.19%) were aged <65 years, 91 (22.8%) were aged 65 years. Elderly patients were more likely to have higher ASA scores (35.7% vs 92.3%; p < 001), Charlson Comorbidity Index (1.8 vs. 5.2, p < 0.001), hyperlipidemia (10.06% vs. 30.76%; p ¼ 0,0005) and coronary heart disease (5.51% vs. 17.58; p ¼ 0.005) compared to younger cohort. Perioperative outcomes (stone free rate, operative time and re-intervention rate) did not show differences between the two groups (p > 0.05). Surgical and medical complication rates were similar between the cohorts (14.28% vs 9.89%; p ¼ 0.38). Multivariate analysis did not identify any predictive factors of complications among the two groups (p > 0.05). Conclusions: In this study, elderly RIRS patients had comparable short term efficacy and perioperative complications to younger patients, despite a higher prevalence of comorbidity. Age itself should not be considered as a risk factor for the development of complications in patients undergoing RIRS for renal stone. © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.
Keywords: RIRS Flexible ureteroscopy Elderly patients Age
1. Introduction ABBREVIATIONS: RIRS, Retrograde Intrarenal Surgery; SFR, stone free rate; ESWL, Eclectro Schock Wave Litothripsy; PCNL, percutaneous nephrolithotomy; ASA, American Society of Anesthesiologists; CT, Computer Tomography; UAS, Ureteral Access Sheath; DJ, double J stent; BMI, body mass index; OT, operative time; SD, standard deviation; CCI, Charlson Comorbidity Index; GA, General Anesthesia. * Corresponding author. Department of Urology, “S.Pio da Pietrelcina” Hospital, Via San Camillo de Lellis,1, 66054 Vasto, Italy. E-mail address: [email protected] (F. Berardinelli).
The worlds population is aging and senior adults are the fastest growing population, particularly so in Western countries. Demographic projections suggest that the world's older population (60 years) is set to rise from 841 million in 2013, to more than 2 billion by 2050 [1]. Although age itself is not an illness, it is the most
http://dx.doi.org/10.1016/j.ijsu.2017.04.062 1743-9191/© 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.
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2.1. Statistical analysis
important contributing factor for perioperative complications, when the overall narrowed margins of organ function reserve are transgressed during the perioperative period [2]. For this reason a more accurate approach to elderly population is very important. Global literature reports an increasing prevalence of urinary stone disease [3,4]. Geriatric stone formers comprise 10e12% of all stone formers [5] and are not only an extension of younger stone forming patients presenting at an older age. Retrograde Intrarenal surgery (RIRS) has gained acceptance as a first-line alternative treatment option for renal stones up to 20 mm [6,7] and in other special circumstances [8,9]. RIRS has potentially higher stone-free rates (SFR) than extracorporeal shock wave lithotripsy (ESWL) and lower morbidity than percutaneous nephrolithotomy (PCNL) [10]. As well as age is an important factor for the ESWL and the PCNL, as the safety of the procedures could be challenged, if it represents a decisive factor for RIRS, must be still clarified. Even if RIRS is a minimally invasive procedure, it is not free of complications (surgical and medical). Few studies have verified whether the outcomes of the RIRS in the elderly population are different from the general population. So elderly patients could be under treatment for hypothetical risks that have never been verified and quantized. The aim of this study was to evaluate the safety and efficacy of RIRS for renal stones in elderly patients.
The two groups were compared in terms of baseline patients characteristics (gender, BMI, ASA score, Hydronephrosis, Arterial hypertension, Alteration of lipid metabolism, Diabetes, Coronary heart disease, Chronic kidney disease, Anticoagulant therapy, previous surgery for renal stone) and stone characteristics (presence of multiple stones, stone diameters) as well as in terms of operative outcomes (use of UAS, operative time (OT), Re-intervention, SFR) and overall complications (intra-op and post-op) graded according to Dindo-Clavien classification. Univariable and multivariable analyses were performed for factors predicting overall complications. For continuous data, variables were presented as mean ± standard deviation (SD). For variables with non-normal distribution, the groups were compared using ManneWhitney U test. Categorical variables were compared using chi-squared test, using, where possible, the Yates correction or the Fisher's exact test. To assess the effect of continuous variables on the dicotomous variable “overall complications” an univariable and multivariable logistic regression model was performed considering the independent variables: BMI, Stone length, Stone width and OT. Significance was set at P < 0.05 corrected. Analysis was performed using Statistica® 8.0 (StatSoft Inc.)
2. Material and methods
3. Results
Data was collected prospectively on patients undergoing RIRS for renal stones from 2013 to 2014 at 5 European centers. Patients was divided in 2 different groups on the basis of age (Group1:<65 y and group 2:>65 y). Patient data included: demographics, medical comorbid conditions, American Society of Anesthesiologists (ASA), anticoagulant therapy and hydronephrosis. Renal stones were evaluated with computed tomography (CT), stone parameters evaluated included: stone size, the presence of multiple stones and past surgery for other renal stone. A sterile urine culture was required before the surgery in all the patients. We excluded cases with a preoperative urinary tract infection due to the potential risk of post-operative sepsis [11]. Patients with severe neurological disorders, pregnancy and cachexya were excluded. Patients who had positive cultures (greater than 100,000 cfu/ml) were treated with appropriate antibiotics based on sensitivity profile at least 7 days and re-evaluated up to obtain sterile culture. All patients underwent RIRS under general or spinal anesthesia, in a standard lithotomy position. At the time of induction, all patients received intravenous broad spectrum antibiotics according to local guidelines and sensitivities. Informed consent was obtained from all patients, and the possible need for a staged procedure in order to obtain satisfactory stone clearance was mentioned. The ureteral access sheath (UAS) and double J (DJ) stent were placed according to surgeon preference. Stone clearance and the integrity of the collecting system were confirmed intraoperatively. The patients were discharged unless complications required hospitalization. The ‘‘stone-free’’ status was defined as no evidence of stones more than 2 mm on one-month postoperative CT. Patients with significant residual fragments, were scheduled for second look RIRS at the time of discharge. Intraoperative and postoperative complications were assessed according to the modified Clavien classification [12]. Perioperative complications were divided into surgical and medical. Surgical complications were considered those directly related to the procedure or perioperative consequences (perforation of pelvis/calyx, ureteral injury, bleeding), whereas medical complications were those conditions that were exacerbated by perioperative stress or intubation and mechanical ventilation (cardiac, gastrointestinal, pulmonary, hematologic, infective or other).
3.1. Patient demographics A total of 399 patients underwent RIRS with holmium laser lithotripsy for renal stones from January 2013 to October 2014. Three hundreds and eight patients (77.19%) were aged <65 years (Group 1) and 91 (22.8%) were aged 65 years (Group 2). The mean age of Group 1 was 48,61 ± 13.16 years while the mean age of Group 2 was 72,1 ± 5.06 years. Group 2 patients had an overall higher ASA score (p < 001), Charlson Comorbidity Index (CCI) (p < 0.001) and were more likely to have hyperlipidemia (p ¼ 0.0005) and coronary heart disease (p ¼ 0.005). However, the rate of arterial hypertension (p ¼ 0.10), diabetes (p ¼ 0.27), chronic kidney disease (p ¼ 1.0) was similar between the groups. Group1 patients were more likely to have to the procedure under general anesthesia (GA) compared to Group 2 patients (80.1% vs. 67%; p ¼ 0.007). Data shown in Table 1. 3.2. Stone characteristics and clearance Stone characteristics were not significantly different between the groups, stone size (p > 0.17) and the presence of multiple stones (p ¼ 0.41) were consistent. Perioperative outcomes did not show differences between the two groups. UAS were more likely to be used in older patients and there is a trend for slightly longer OT and lower stone free rates in Group 2 patients, but this was not statistically significant, (p > 0.05). Re-intervention rates were lower in Group 2 patients than Group 1 patients, however again this difference was not statistically different (p > 0.05). Data is shown in Table 1. 3.3. Perioperative outcomes and complications The complication rate for Group 1 patients is 14.2%, while the rate for Group 2 patients is 9.8%. A total of 44 complications were noted in Group 1, 21 (47%) were surgical complications and 23 (53%) were medical complications. Of note in the Group 1, three patients (1%) were re-admitted following discharge for obstructive pyelonephritis (Clavien IIIa) and treated endoscopically (DJ stent placement) with no major sequences. The rest of the complication
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Table 1 Comparison of perioperative outcomes. Overall patients characteristics No pts (%) Age (mean ± SD) No male (%) BMI (kg/m2) (mean ± SD) ASA score (3) CCI Hyperlipidemia Coronary heart disease Arterial hypertension Diabetes Hydronephrosis Chronic kidney disease Anticoagulant therapy Past surgery for renal stone stone characteristics Presence of multiple stones Stone length (mm) Stone width (mm) Presence of a preoperative DJ Acid Uric composition perioperative outcomes General anesthesia Use of UAS OT (min) (mean ± SD) LOS (days) (mean ± SD) Stone-free status Re-intervention a b
399 (100.0) 53,93 (13.65) 256 (64.16) 26,49 (4.17) 194 (48.62) 3 59 (14.79) 33 (8.27) 103 (25.81) 46 (11.52) 171 (42.85) 13 (3.25) 13 (3.25) 140 (35.08) 161 (40,35) 12,2 (5,31) 9,26 (4.41) 100 (35.06) 18 (4.51) 308 (77,19) 317 (79,44) 62,08 (31.82) 2.7 (1.9) 282 (70.67) 378 (9.27)
Group 1 (<65 y.o.)
Group 2 (65 y.o.)
e 308 (77.19) 48.6 (13.16) 202 (65.58) 26.25 (4.1) 110 (35.71) 1.8 31 (10.06) 17 (5.51) 71 (23.05) 32 (10.38) 135 (43.83) 10 (3.24) 5 (1.62) 106 (34.41) e 130 (42.2) 11.95 (5.14) 9.15 (4.22) 63 (15.79) 14 (4.54) e 247 (80,19) 242 (78.57) 61.42 (30.49) 2.5 (1.7) 222 (72.07) 32 (10.38)
e 91 (22.8) 72.1 (5.06) 54 (59.3) 27.27 (4.23) 84 (92.3) 5.2 28 (30.76) 16 (17.58) 32 (35.16) 14 (15.38) 36 (39.56) 3 (3.29) 8 (8.79) 34 (37.36) e 31 (34.06) 13.05 (5.79) 9.65 (5.02) 37 (9.28) 4 (4.39) e 61 (67,03) 75 (82.41) 64.31 (31.87) 2.8 (1.8) 60 (65.93) 5 (5.49)
P value
<0.001 0.61b 0.065 <0.001b <0.001b 0.0005a 0.005a 0.10b 0.27b 0.72b 1.0a 0.19a 0.81b 0.41b 0.17 0.69 0.78 0.61 0.007a 0.85b 0.68 0.1 0.70b 0.21a
Fisher exact test (two-tailed). Yates Correction.
were Clavien II. In Group 2, 5 (56%) were surgical and 4 (44%) were medical complications. All complications were Clavien II: Three patients experience post-operative fever and one patients developed non obstructive pyelonephritis, all conditions were treated pharmacologically. Five patients in Group 2 also had surgical complications, this included 2 episodes of haematuria, 2 perforations of pelvis/ calyx and one ureteral injury, all of which were treated with DJ placement. Overall complication rate was similar between younger and elderly patients (14.28% vs 9.89%; p ¼ 0.38). Data is shown in Table 2).
and no associations or predictive factors for complications were identified (see Table 3). Data is show in Table 4.
4. Discussion Worldwide, the incidence of urolithiasis is steadily increasing and the prevalence varies from 4 to 20% [13]. The incidence of renal stones in older patients is expected to increase as the general population ages, especially in developed countries. Over the last 10 years, RIRS has become an increasingly important option for the treatment of the majority of kidney stones even in the most
3.4. Multiple logistic regression analysis In a multiple logistic regression analysis, on univariate analysis and multivariable analyses no factor was found so be significant
Table 2 Comparison of complications between Group 1 (<65 y.o.) and Group 2 (>65 y.o.). Group 1 (<65 y.o.)
Group 2 (>65 y.o.)
P value
44
9
0.38
10 1 20
2 0 3
Overall complications Grade I Bleeding flank pain Fever Grade II Perforation of pelvis/calyx Ureteral injury Non obstructive pyelonephritis Grade IIIa Obstructive pyelonephritis
6 2 2
2 1 1
3
0
Total surgical complications Total medical complications
21 23
5 4
Table 3 Multivariate analysis demonstrating factors predicting overall complications. Variables
Complication
Mann-Withney test for continuous dependent variables Age (mean ± SD) 53,9 (13,65) BMI (kg/m2) 26,49 (4,17) OT (min) (mean ± SD) 62,08 (31,82) Stone length (mm) 12,3 (5,31) Stone width (mm) 9,26 (4,41) Chi squared test for dichotomous dependent variables Arterial hypertension 20 (5,25) Hyperlipidemia 17 (4,27) Diabetes 7 (1,75) Coronary heart disease 8 (18,2) Chronic kidney disease 4 (6,8) Anticoagulant therapy 1 (2,3) Presence of multiple stones 26 (6,53) Use of UAS 41 (93,2) Stone-free status 28 (7,03) ASA score (3) 34 (8,5) Hydronephrosis 18 (4,52) a b
Yates Correction. Fisher exact test (two-tailed).
P value 0,52 0,527 0,059 0,33 0,73 0,65 0,12 0,65b 0,11a 0, 090a 0,39a 0,46 0,58a 0,22a 0,65a 0,43a
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Table 4 Logistic univariable and multivariable regression demonstrating factors predicting overall complications. Univariable
Age (years) BMI (kg/m2) OT (min) Stone length (mm) Stone width (mm)
Multivariable
OR (95%CI)
p
OR (95%CI)
p
1008 (0,013) 1024 (0,044) 1007 (0,001) 1021 (0,032) 0,98 (0,077)
0,45 0,49 0,10 0,43 0,75
1005 (0,016) 1010 (0,059) 1006 (0,002) 1085 (0,016) 0,896 (0,23)
0,279
complicated clinical scenarios such as pregnancy, obesity, coagulopathy, large renal stones, calyceal diverticula, and kidney malformations [9]. However, at the best of our knowledge, no studies compared the outcomes of RIRS between an aged and young cohorts and there is a lack of general agreement about the best treatment of elderly population affected by renal stone disease. In our study we evaluated the clinical and surgical outcomes of RIRS for renal stones in patients aged 65 years. The analysis of 399 RIRS demonstrates the procedure as a safe and effective option for geriatric patients. The overall SFR after a single procedure was 72% and 65.9%, in young and elderly patients, respectively (p ¼ 0.7). This finding is comparable to SFR of 65e79% reported in general population series [14]. Other peri-perative outcomes like operative time, use of UAS, length of stay and re-intervention rate were not influenced by age. Due to a prolonged operative time, larger stone size, and patient or physician preference, a second-look procedure was necessary in 10.3% and 5.4% of the cases in Group 1 and 2, respectively (p ¼ 0.21). We do not regard this as a treatment failure of the first procedure, but rather as a necessary part of a planned staged procedure to ensure the best stone clearance. Despite baseline characteristics of the patients demonstrating an elderly cohort with greater comorbidities, higher CCI and ASA scores, no differences in the severity or number of intra- and postoperative complications were recorded (14.2% vs. 9.8%). Advanced age and the presence of comorbidities does not increase the rate of surgical as well as medical complications related to cardiovascular, infective and respiratory dysfunction. No major complications were recorded and only minor complications occurred in Group 2 patients (2 episodes of post-operative fever and one case of nonobstructive pyelonephritis) all complications were managed by conservative therapy. Elderly patients from Group 2 underwent RIRS more frequently under spinal anesthesia than patients from Group 1. This is due anesthesiologist preference as Spinal and epidural anesthesia has fewer side effects and risks than general anesthesia (GA). However, spinal anesthesia is associated with renal movement caused by respiration [15]. This can make RIRS more difficult, explaining our results of a longer OT and of a lower SFR in this group. There is an abundance of reports in the literature examining PCNL in elderly patient cohort, but there is a relative dearth of information regarding RIRS in this population. Akman et al., performed a retrospective matched-pair analysis of elderly patients (age 65 years) who underwent RIRS compared with patients who underwent PCNL [16]. In this study, the overall complication rate after RIRS was 7.1%. This is comparable to our result of 9.8% and not much different from the general population risk (13.3%) [17,18]. However, this study was not designed to detect differences between age groups, the authors concluded that RIRS can be performed safely in geriatric patients. In general surgery, Hermans et al. evaluated the impact of comorbidities on the outcome in elderly patients. The authors found that the type and number of comorbidities influence post-operative mortality and morbidity that were more frequent in elderly compared to younger patients (vs
50% 24%) [19]. Our results on RIRS refute these findings of a strong association between increased age with an increase in both mortality and morbidity. Predictive factors were not identified (for all variables p > 0.05) possibly because of low complications rate and low statistical power and because RIRS is characterized by minimal tissue trauma and by minimal changes in stress parameters (IL-6 and CRP) [20]. A low interventional stress corresponds to decrease the rate of medical complications as reported in literature [21]. These aspects may explain the low rate of complications after RIRS in general population and the absence of a higher rate in elderly patients. Is it reasonable to offer RIRS as a safe procedure even in elderly people? Each surgeon has his own personal feeling about the safety of a procedure derived from experience. However feelings are no longer acceptable in evidence-based medical practice. As inconsistency in reporting outcomes postRIRS in elderly people is still unquestionable, with this study we hope to fill this gap. Age alone should not prevent elderly patients from receiving standard treatment for their renal stone and they should receive the same type of surgery as younger patients. There are some limitations that we should report. First the age cut-off used to define elderly people. For this study, we chose to define ‘elderly’ as individual's 65 years of age, however there is no United Nations standard numerical criterion for this definition. The number of elderly patients included is relatively limited (23%) but it mirrors the real scenario of current public health care. Another limitation could be the possible patients selection bias. The choice of whether a patient with renal stone should be observed, or offered ESWL, RIRS, or PCNL depends on many factors, including the size and location of the stone, surgeon preferences as well as the patient's clinical condition. The recruitment of elderly patients in this study is based exclusively on these criteria, without bias resulting from a patients selection based on a better performance status. Also we should acknowledge that we have not collected data about prostate size, a possible factor influencing the feasibility and efficacy in the RIRS. The prostate can enlarge significantly as a man ages [22]. During cystoscopy, a large prostate, especially those with a median lobe can dislocate the ureteral orifice making access to the kidney difficult. Furthermore, large prostate tend to bleed easily, obscuring the view. Further studies are needed to evaluate if prostate enlargement is a clinical predictors of procedure failure or switching to PCNL. 5. Conclusions The increasing age of the stone population and the increased comorbidities experienced by these patients is an issue of real and growing concern to endourologists. Our study, for the first time, found no differences between young and elderly people after RIRS in terms of outcomes and complications. This means that RIRS is a safe procedure even in aged population, where there is an increase of comorbidities and surgical risks. More studies are necessary to confirm these encouraging results. Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors. Informed consent was obtained from all individual participants included in the study.
F. Berardinelli et al. / International Journal of Surgery 42 (2017) 147e151
Sources of funding None. Author contribution F Berardinelli: Protocol/project development, Data collection or management, Data analysis. Manuscript writing/editing. P De Francesco: Protocol/project development, Data collection or management, Manuscript writing/editing. M Marchioni: Data collection or management, Data analysis. N Cera: Data analysis. S Proietti: Data collection or management. D Hennessey: Data collection or management. O Dalpiaz: Data collection or management. C Cracco: Data collection or management. C Scoffone: Data collection or management. G Giusti: Data collection or management. L Cindolo: Protocol/project development, Data collection or management, Manuscript writing/editing. L Schips: Protocol/project development, Data collection or management, Manuscript writing/editing. Conflicts of interest Guido Giusti is a consultant for Boston Scientific, Cook Medical, Porges-Coloplast, Karl Storz. Cesare Mario Scoffone is a consultant for Boston Scientific, Cook Medical, Porges-Coloplast, Karl Storz. F. Berardinelli, L. Cindolo, P. De Francesco, N. Cera, M. Marchioni, S. Proietti, D. Hennessey, O. Dalpiaz, C. Cracco and L. Schips have nothing to disclose. Guarantor F. Berardinelli. Research registration unique identifying number (UIN) researchregistry2275. References [1] S. Chatterji, J. Byles, D. Cutler, T. Seeman, E. Verdes, Health, functioning, and disability in older adultsdpresent status and future implications, Lancet 385 (2015) 563e575, http://dx.doi.org/10.1016/S0140-6736(14)61462-8.
151
[2] H. Hu, Y. Lu, D. He, et al., Comparison of minimally invasive percutaneous nephrolithotomy and exible ureteroscopy for the treatment of intermediate proximal ureteral and renal stones in the elderly, Urolithiasis 44 (2016) 427. [3] D. Prezioso, E. Illiano, G. Piccinocchi, et al., Urolithiasis in Italy: an epidemiological study, Arch. Ital. Urol. Androl. 86 (2014) 99e102. [4] J. Bauer, A. Kahlmeyer, R. Stredele, B.G. Volkmer, Inpatient therapy of urinary stones in Germany: development of the G-DRG system, Urol. A 53 (2014) 1764e1771. [5] A. Sahin, N. Atsu, E. Erdem, et al., Percutaneous nephrolithotomy in patients aged 60 years or older, J. Endourol. 15 (2001) 489e491, http://dx.doi.org/ 10.1089/089277901750299276. [6] F. Berardinelli, S. Proietti, L. Cindolo, A prospective multicenter European study on flexible ureterorenoscopy for the management of renal stone, Int. Braz. J. Urol. 42 (2016) 479e486, http://dx.doi.org/10.1590/S16775538.IBJU.2015.0528. [7] G. Giusti, S. Proietti, L. Villa, et al., Current standard technique for modern flexible ureteroscopy: tips and tricks, Eur. Urol. 70 (2016) 188e194, http:// dx.doi.org/10.1016/j.eururo.2016.03.035. [8] G. Giusti, S. Proietti, R. Peschechera, et al., Sky is no limit for ureteroscopy: extending the indications and special circumstances, World J. Urol. 33 (2015) 257e273. [9] G. Giusti, S. Proietti, L. Cindolo, et al., Is retrograde intrarenal surgery a viable treatment option for renal stones in patients with solitary kidney? World J. Urol. 33 (2015) 309e314. [10] S. De, R. Autorino, F.J. Kim, et al., Percutaneous nephrolithotomy versus retrograde intrarenal surgery: a systematic review and meta-analysis, Eur. Urol. 67 (2014) 125e137, http://dx.doi.org/10.1016/j.eururo.2014.07.003. [11] B.R. Matlaga, J.E. Lingeman, Surgical management of stones: new technology, Adv. Chronic Kidney Dis. 16 (2009) 60e64. [12] D. Dindo, N. Demartines, P.A. Clavien, Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey, Ann. Surg. 240 (2004) 205e213. [13] A. Trinchieri, Epidemiology of urolithiasis: an update, Eur. Urol. 67 (2015) 125. [14] A. Breda, O. Ogunyemi, J.T. Leppert, et al., Flexible ureteroscopy and laser lithotripsy for multiple unilateral intrarenal stones, Eur. Urol. 55 (2009) 1190e1196. [15] Emiliani E, Talso M, Baghdadi M, The use of Apnea during ureteroscopy. Urology doi:10.1016/j.urology.2016.06.016. [Epub ahead of print]. [16] T. Akman, M. Binbay, M. Ugurlu, et al., Outcomes of retrograde intrarenal surgery compared with percutaneous nephrolithotomy in elderly patients with moderate-size kidney stones: a matched-pair analysis, J. Endourol. 26 (2012) 625. [17] F. Berardinelli, L. Cindolo, P. De Francesco, et al., The surgical experience influences the safety of retrograde intrarenal surgery for kidney stones: a propensity score analysis, Urolithiasis (2016) [Epub ahead of print]. [18] F. Berardinelli, P. De Francesco, M. Marchioni, et al., Infective complications after retrograde intrarenal surgery: a new standardized classification system, Int. Urol. Nephrol. 48 (2016) 1757. [19] E. Hermans, P.M. van Schaik, H.A. Prins, et al., Outcome of colonic surgery in elderly patients with colon cancer, J. Oncol. (2010) 865908. [20] S. Kruck, M. Sonnleithner, J. Hennenlotter, et al., Interventional stress in renal stone treatment, J. Endourol. 25 (2011) 1069. [21] P. Kragsbjerg, H. Holmberg, T. Vikerfors, Serum concentrations of interleukin6, tumour necrosis factor-alpha, and C- reactive protein in patients undergoing major operations, Eur. J. Surg. 161 (1995) 17. [22] S.J. Jacobsen, D.J. Jacobson, C.J. Girman, et al., Treatment for benign prostatic hyperplasia among community dwelling men: the Olmsted County study of urinary symptoms and health status, J. Urol. 162 (1999) 1301.
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Original Research
RIRS in the elderly: Is it feasible and safe? F. Berardinelli, MD, FEBU a, *, P. De Francesco a, M. Marchioni a, N. Cera b, S. Proietti c, D. Hennessey d, O. Dalpiaz e, C. Cracco f, C. Scoffone f, G. Giusti c, L. Cindolo a, L. Schips a a
Department of Urology, “S. Pio da Pietrelcina’’ Hospital, Vasto, CH, Italy Faculty of Psychology and Educational Sciences, University of Porto, Porto, Portugal c Urology Dept, Urological Research Institute, IRCCS Ospedale San Raffaele, Ville Turro Division, Milan, Italy d Department of Urology, Austin Health, Melbourne, Australia e €t, Graz, Austria Urologische Klinik, Medizinische Universita f Urologia, Ospedale Cottolengo, Torino, Italy b
h i g h l i g h t s RIRS has gain more acceptance as first line therapy in renal stones up to 2 cm. RIRS is an effective and safe technique regardless the age of patients. RIRS is a surgical technique with a low complication rate.
a r t i c l e i n f o
a b s t r a c t
Article history: Received 26 April 2017 Accepted 27 April 2017 Available online 3 May 2017
Background: The aim of this study was to compare the safety and efficacy of RIRS in men 65 years to those <65 years. Materials and methods: Patients who underwent RIRS were prospectively collected from March 2013 to March 2014 in 5 European centers. Perioperative outcomes and complications in elderly men were compared with men <65 years. Univariable and multivariable analyses were performed for factors predicting overall complications. The groups were compared using ManneWhitney U test. Categorical variables were compared using chi-squared test and the Yates correction or the Fisher's exact test. Results: A total of 399 patients with renal stones were included, 308 (77.19%) were aged <65 years, 91 (22.8%) were aged 65 years. Elderly patients were more likely to have higher ASA scores (35.7% vs 92.3%; p < 001), Charlson Comorbidity Index (1.8 vs. 5.2, p < 0.001), hyperlipidemia (10.06% vs. 30.76%; p ¼ 0,0005) and coronary heart disease (5.51% vs. 17.58; p ¼ 0.005) compared to younger cohort. Perioperative outcomes (stone free rate, operative time and re-intervention rate) did not show differences between the two groups (p > 0.05). Surgical and medical complication rates were similar between the cohorts (14.28% vs 9.89%; p ¼ 0.38). Multivariate analysis did not identify any predictive factors of complications among the two groups (p > 0.05). Conclusions: In this study, elderly RIRS patients had comparable short term efficacy and perioperative complications to younger patients, despite a higher prevalence of comorbidity. Age itself should not be considered as a risk factor for the development of complications in patients undergoing RIRS for renal stone. © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.
Keywords: RIRS Flexible ureteroscopy Elderly patients Age
1. Introduction ABBREVIATIONS: RIRS, Retrograde Intrarenal Surgery; SFR, stone free rate; ESWL, Eclectro Schock Wave Litothripsy; PCNL, percutaneous nephrolithotomy; ASA, American Society of Anesthesiologists; CT, Computer Tomography; UAS, Ureteral Access Sheath; DJ, double J stent; BMI, body mass index; OT, operative time; SD, standard deviation; CCI, Charlson Comorbidity Index; GA, General Anesthesia. * Corresponding author. Department of Urology, “S.Pio da Pietrelcina” Hospital, Via San Camillo de Lellis,1, 66054 Vasto, Italy. E-mail address: [email protected] (F. Berardinelli).
The worlds population is aging and senior adults are the fastest growing population, particularly so in Western countries. Demographic projections suggest that the world's older population (60 years) is set to rise from 841 million in 2013, to more than 2 billion by 2050 [1]. Although age itself is not an illness, it is the most
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2.1. Statistical analysis
important contributing factor for perioperative complications, when the overall narrowed margins of organ function reserve are transgressed during the perioperative period [2]. For this reason a more accurate approach to elderly population is very important. Global literature reports an increasing prevalence of urinary stone disease [3,4]. Geriatric stone formers comprise 10e12% of all stone formers [5] and are not only an extension of younger stone forming patients presenting at an older age. Retrograde Intrarenal surgery (RIRS) has gained acceptance as a first-line alternative treatment option for renal stones up to 20 mm [6,7] and in other special circumstances [8,9]. RIRS has potentially higher stone-free rates (SFR) than extracorporeal shock wave lithotripsy (ESWL) and lower morbidity than percutaneous nephrolithotomy (PCNL) [10]. As well as age is an important factor for the ESWL and the PCNL, as the safety of the procedures could be challenged, if it represents a decisive factor for RIRS, must be still clarified. Even if RIRS is a minimally invasive procedure, it is not free of complications (surgical and medical). Few studies have verified whether the outcomes of the RIRS in the elderly population are different from the general population. So elderly patients could be under treatment for hypothetical risks that have never been verified and quantized. The aim of this study was to evaluate the safety and efficacy of RIRS for renal stones in elderly patients.
The two groups were compared in terms of baseline patients characteristics (gender, BMI, ASA score, Hydronephrosis, Arterial hypertension, Alteration of lipid metabolism, Diabetes, Coronary heart disease, Chronic kidney disease, Anticoagulant therapy, previous surgery for renal stone) and stone characteristics (presence of multiple stones, stone diameters) as well as in terms of operative outcomes (use of UAS, operative time (OT), Re-intervention, SFR) and overall complications (intra-op and post-op) graded according to Dindo-Clavien classification. Univariable and multivariable analyses were performed for factors predicting overall complications. For continuous data, variables were presented as mean ± standard deviation (SD). For variables with non-normal distribution, the groups were compared using ManneWhitney U test. Categorical variables were compared using chi-squared test, using, where possible, the Yates correction or the Fisher's exact test. To assess the effect of continuous variables on the dicotomous variable “overall complications” an univariable and multivariable logistic regression model was performed considering the independent variables: BMI, Stone length, Stone width and OT. Significance was set at P < 0.05 corrected. Analysis was performed using Statistica® 8.0 (StatSoft Inc.)
2. Material and methods
3. Results
Data was collected prospectively on patients undergoing RIRS for renal stones from 2013 to 2014 at 5 European centers. Patients was divided in 2 different groups on the basis of age (Group1:<65 y and group 2:>65 y). Patient data included: demographics, medical comorbid conditions, American Society of Anesthesiologists (ASA), anticoagulant therapy and hydronephrosis. Renal stones were evaluated with computed tomography (CT), stone parameters evaluated included: stone size, the presence of multiple stones and past surgery for other renal stone. A sterile urine culture was required before the surgery in all the patients. We excluded cases with a preoperative urinary tract infection due to the potential risk of post-operative sepsis [11]. Patients with severe neurological disorders, pregnancy and cachexya were excluded. Patients who had positive cultures (greater than 100,000 cfu/ml) were treated with appropriate antibiotics based on sensitivity profile at least 7 days and re-evaluated up to obtain sterile culture. All patients underwent RIRS under general or spinal anesthesia, in a standard lithotomy position. At the time of induction, all patients received intravenous broad spectrum antibiotics according to local guidelines and sensitivities. Informed consent was obtained from all patients, and the possible need for a staged procedure in order to obtain satisfactory stone clearance was mentioned. The ureteral access sheath (UAS) and double J (DJ) stent were placed according to surgeon preference. Stone clearance and the integrity of the collecting system were confirmed intraoperatively. The patients were discharged unless complications required hospitalization. The ‘‘stone-free’’ status was defined as no evidence of stones more than 2 mm on one-month postoperative CT. Patients with significant residual fragments, were scheduled for second look RIRS at the time of discharge. Intraoperative and postoperative complications were assessed according to the modified Clavien classification [12]. Perioperative complications were divided into surgical and medical. Surgical complications were considered those directly related to the procedure or perioperative consequences (perforation of pelvis/calyx, ureteral injury, bleeding), whereas medical complications were those conditions that were exacerbated by perioperative stress or intubation and mechanical ventilation (cardiac, gastrointestinal, pulmonary, hematologic, infective or other).
3.1. Patient demographics A total of 399 patients underwent RIRS with holmium laser lithotripsy for renal stones from January 2013 to October 2014. Three hundreds and eight patients (77.19%) were aged <65 years (Group 1) and 91 (22.8%) were aged 65 years (Group 2). The mean age of Group 1 was 48,61 ± 13.16 years while the mean age of Group 2 was 72,1 ± 5.06 years. Group 2 patients had an overall higher ASA score (p < 001), Charlson Comorbidity Index (CCI) (p < 0.001) and were more likely to have hyperlipidemia (p ¼ 0.0005) and coronary heart disease (p ¼ 0.005). However, the rate of arterial hypertension (p ¼ 0.10), diabetes (p ¼ 0.27), chronic kidney disease (p ¼ 1.0) was similar between the groups. Group1 patients were more likely to have to the procedure under general anesthesia (GA) compared to Group 2 patients (80.1% vs. 67%; p ¼ 0.007). Data shown in Table 1. 3.2. Stone characteristics and clearance Stone characteristics were not significantly different between the groups, stone size (p > 0.17) and the presence of multiple stones (p ¼ 0.41) were consistent. Perioperative outcomes did not show differences between the two groups. UAS were more likely to be used in older patients and there is a trend for slightly longer OT and lower stone free rates in Group 2 patients, but this was not statistically significant, (p > 0.05). Re-intervention rates were lower in Group 2 patients than Group 1 patients, however again this difference was not statistically different (p > 0.05). Data is shown in Table 1. 3.3. Perioperative outcomes and complications The complication rate for Group 1 patients is 14.2%, while the rate for Group 2 patients is 9.8%. A total of 44 complications were noted in Group 1, 21 (47%) were surgical complications and 23 (53%) were medical complications. Of note in the Group 1, three patients (1%) were re-admitted following discharge for obstructive pyelonephritis (Clavien IIIa) and treated endoscopically (DJ stent placement) with no major sequences. The rest of the complication
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Table 1 Comparison of perioperative outcomes. Overall patients characteristics No pts (%) Age (mean ± SD) No male (%) BMI (kg/m2) (mean ± SD) ASA score (3) CCI Hyperlipidemia Coronary heart disease Arterial hypertension Diabetes Hydronephrosis Chronic kidney disease Anticoagulant therapy Past surgery for renal stone stone characteristics Presence of multiple stones Stone length (mm) Stone width (mm) Presence of a preoperative DJ Acid Uric composition perioperative outcomes General anesthesia Use of UAS OT (min) (mean ± SD) LOS (days) (mean ± SD) Stone-free status Re-intervention a b
399 (100.0) 53,93 (13.65) 256 (64.16) 26,49 (4.17) 194 (48.62) 3 59 (14.79) 33 (8.27) 103 (25.81) 46 (11.52) 171 (42.85) 13 (3.25) 13 (3.25) 140 (35.08) 161 (40,35) 12,2 (5,31) 9,26 (4.41) 100 (35.06) 18 (4.51) 308 (77,19) 317 (79,44) 62,08 (31.82) 2.7 (1.9) 282 (70.67) 378 (9.27)
Group 1 (<65 y.o.)
Group 2 (65 y.o.)
e 308 (77.19) 48.6 (13.16) 202 (65.58) 26.25 (4.1) 110 (35.71) 1.8 31 (10.06) 17 (5.51) 71 (23.05) 32 (10.38) 135 (43.83) 10 (3.24) 5 (1.62) 106 (34.41) e 130 (42.2) 11.95 (5.14) 9.15 (4.22) 63 (15.79) 14 (4.54) e 247 (80,19) 242 (78.57) 61.42 (30.49) 2.5 (1.7) 222 (72.07) 32 (10.38)
e 91 (22.8) 72.1 (5.06) 54 (59.3) 27.27 (4.23) 84 (92.3) 5.2 28 (30.76) 16 (17.58) 32 (35.16) 14 (15.38) 36 (39.56) 3 (3.29) 8 (8.79) 34 (37.36) e 31 (34.06) 13.05 (5.79) 9.65 (5.02) 37 (9.28) 4 (4.39) e 61 (67,03) 75 (82.41) 64.31 (31.87) 2.8 (1.8) 60 (65.93) 5 (5.49)
P value
<0.001 0.61b 0.065 <0.001b <0.001b 0.0005a 0.005a 0.10b 0.27b 0.72b 1.0a 0.19a 0.81b 0.41b 0.17 0.69 0.78 0.61 0.007a 0.85b 0.68 0.1 0.70b 0.21a
Fisher exact test (two-tailed). Yates Correction.
were Clavien II. In Group 2, 5 (56%) were surgical and 4 (44%) were medical complications. All complications were Clavien II: Three patients experience post-operative fever and one patients developed non obstructive pyelonephritis, all conditions were treated pharmacologically. Five patients in Group 2 also had surgical complications, this included 2 episodes of haematuria, 2 perforations of pelvis/ calyx and one ureteral injury, all of which were treated with DJ placement. Overall complication rate was similar between younger and elderly patients (14.28% vs 9.89%; p ¼ 0.38). Data is shown in Table 2).
and no associations or predictive factors for complications were identified (see Table 3). Data is show in Table 4.
4. Discussion Worldwide, the incidence of urolithiasis is steadily increasing and the prevalence varies from 4 to 20% [13]. The incidence of renal stones in older patients is expected to increase as the general population ages, especially in developed countries. Over the last 10 years, RIRS has become an increasingly important option for the treatment of the majority of kidney stones even in the most
3.4. Multiple logistic regression analysis In a multiple logistic regression analysis, on univariate analysis and multivariable analyses no factor was found so be significant
Table 2 Comparison of complications between Group 1 (<65 y.o.) and Group 2 (>65 y.o.). Group 1 (<65 y.o.)
Group 2 (>65 y.o.)
P value
44
9
0.38
10 1 20
2 0 3
Overall complications Grade I Bleeding flank pain Fever Grade II Perforation of pelvis/calyx Ureteral injury Non obstructive pyelonephritis Grade IIIa Obstructive pyelonephritis
6 2 2
2 1 1
3
0
Total surgical complications Total medical complications
21 23
5 4
Table 3 Multivariate analysis demonstrating factors predicting overall complications. Variables
Complication
Mann-Withney test for continuous dependent variables Age (mean ± SD) 53,9 (13,65) BMI (kg/m2) 26,49 (4,17) OT (min) (mean ± SD) 62,08 (31,82) Stone length (mm) 12,3 (5,31) Stone width (mm) 9,26 (4,41) Chi squared test for dichotomous dependent variables Arterial hypertension 20 (5,25) Hyperlipidemia 17 (4,27) Diabetes 7 (1,75) Coronary heart disease 8 (18,2) Chronic kidney disease 4 (6,8) Anticoagulant therapy 1 (2,3) Presence of multiple stones 26 (6,53) Use of UAS 41 (93,2) Stone-free status 28 (7,03) ASA score (3) 34 (8,5) Hydronephrosis 18 (4,52) a b
Yates Correction. Fisher exact test (two-tailed).
P value 0,52 0,527 0,059 0,33 0,73 0,65 0,12 0,65b 0,11a 0, 090a 0,39a 0,46 0,58a 0,22a 0,65a 0,43a
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Table 4 Logistic univariable and multivariable regression demonstrating factors predicting overall complications. Univariable
Age (years) BMI (kg/m2) OT (min) Stone length (mm) Stone width (mm)
Multivariable
OR (95%CI)
p
OR (95%CI)
p
1008 (0,013) 1024 (0,044) 1007 (0,001) 1021 (0,032) 0,98 (0,077)
0,45 0,49 0,10 0,43 0,75
1005 (0,016) 1010 (0,059) 1006 (0,002) 1085 (0,016) 0,896 (0,23)
0,279
complicated clinical scenarios such as pregnancy, obesity, coagulopathy, large renal stones, calyceal diverticula, and kidney malformations [9]. However, at the best of our knowledge, no studies compared the outcomes of RIRS between an aged and young cohorts and there is a lack of general agreement about the best treatment of elderly population affected by renal stone disease. In our study we evaluated the clinical and surgical outcomes of RIRS for renal stones in patients aged 65 years. The analysis of 399 RIRS demonstrates the procedure as a safe and effective option for geriatric patients. The overall SFR after a single procedure was 72% and 65.9%, in young and elderly patients, respectively (p ¼ 0.7). This finding is comparable to SFR of 65e79% reported in general population series [14]. Other peri-perative outcomes like operative time, use of UAS, length of stay and re-intervention rate were not influenced by age. Due to a prolonged operative time, larger stone size, and patient or physician preference, a second-look procedure was necessary in 10.3% and 5.4% of the cases in Group 1 and 2, respectively (p ¼ 0.21). We do not regard this as a treatment failure of the first procedure, but rather as a necessary part of a planned staged procedure to ensure the best stone clearance. Despite baseline characteristics of the patients demonstrating an elderly cohort with greater comorbidities, higher CCI and ASA scores, no differences in the severity or number of intra- and postoperative complications were recorded (14.2% vs. 9.8%). Advanced age and the presence of comorbidities does not increase the rate of surgical as well as medical complications related to cardiovascular, infective and respiratory dysfunction. No major complications were recorded and only minor complications occurred in Group 2 patients (2 episodes of post-operative fever and one case of nonobstructive pyelonephritis) all complications were managed by conservative therapy. Elderly patients from Group 2 underwent RIRS more frequently under spinal anesthesia than patients from Group 1. This is due anesthesiologist preference as Spinal and epidural anesthesia has fewer side effects and risks than general anesthesia (GA). However, spinal anesthesia is associated with renal movement caused by respiration [15]. This can make RIRS more difficult, explaining our results of a longer OT and of a lower SFR in this group. There is an abundance of reports in the literature examining PCNL in elderly patient cohort, but there is a relative dearth of information regarding RIRS in this population. Akman et al., performed a retrospective matched-pair analysis of elderly patients (age 65 years) who underwent RIRS compared with patients who underwent PCNL [16]. In this study, the overall complication rate after RIRS was 7.1%. This is comparable to our result of 9.8% and not much different from the general population risk (13.3%) [17,18]. However, this study was not designed to detect differences between age groups, the authors concluded that RIRS can be performed safely in geriatric patients. In general surgery, Hermans et al. evaluated the impact of comorbidities on the outcome in elderly patients. The authors found that the type and number of comorbidities influence post-operative mortality and morbidity that were more frequent in elderly compared to younger patients (vs
50% 24%) [19]. Our results on RIRS refute these findings of a strong association between increased age with an increase in both mortality and morbidity. Predictive factors were not identified (for all variables p > 0.05) possibly because of low complications rate and low statistical power and because RIRS is characterized by minimal tissue trauma and by minimal changes in stress parameters (IL-6 and CRP) [20]. A low interventional stress corresponds to decrease the rate of medical complications as reported in literature [21]. These aspects may explain the low rate of complications after RIRS in general population and the absence of a higher rate in elderly patients. Is it reasonable to offer RIRS as a safe procedure even in elderly people? Each surgeon has his own personal feeling about the safety of a procedure derived from experience. However feelings are no longer acceptable in evidence-based medical practice. As inconsistency in reporting outcomes postRIRS in elderly people is still unquestionable, with this study we hope to fill this gap. Age alone should not prevent elderly patients from receiving standard treatment for their renal stone and they should receive the same type of surgery as younger patients. There are some limitations that we should report. First the age cut-off used to define elderly people. For this study, we chose to define ‘elderly’ as individual's 65 years of age, however there is no United Nations standard numerical criterion for this definition. The number of elderly patients included is relatively limited (23%) but it mirrors the real scenario of current public health care. Another limitation could be the possible patients selection bias. The choice of whether a patient with renal stone should be observed, or offered ESWL, RIRS, or PCNL depends on many factors, including the size and location of the stone, surgeon preferences as well as the patient's clinical condition. The recruitment of elderly patients in this study is based exclusively on these criteria, without bias resulting from a patients selection based on a better performance status. Also we should acknowledge that we have not collected data about prostate size, a possible factor influencing the feasibility and efficacy in the RIRS. The prostate can enlarge significantly as a man ages [22]. During cystoscopy, a large prostate, especially those with a median lobe can dislocate the ureteral orifice making access to the kidney difficult. Furthermore, large prostate tend to bleed easily, obscuring the view. Further studies are needed to evaluate if prostate enlargement is a clinical predictors of procedure failure or switching to PCNL. 5. Conclusions The increasing age of the stone population and the increased comorbidities experienced by these patients is an issue of real and growing concern to endourologists. Our study, for the first time, found no differences between young and elderly people after RIRS in terms of outcomes and complications. This means that RIRS is a safe procedure even in aged population, where there is an increase of comorbidities and surgical risks. More studies are necessary to confirm these encouraging results. Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors. Informed consent was obtained from all individual participants included in the study.
F. Berardinelli et al. / International Journal of Surgery 42 (2017) 147e151
Sources of funding None. Author contribution F Berardinelli: Protocol/project development, Data collection or management, Data analysis. Manuscript writing/editing. P De Francesco: Protocol/project development, Data collection or management, Manuscript writing/editing. M Marchioni: Data collection or management, Data analysis. N Cera: Data analysis. S Proietti: Data collection or management. D Hennessey: Data collection or management. O Dalpiaz: Data collection or management. C Cracco: Data collection or management. C Scoffone: Data collection or management. G Giusti: Data collection or management. L Cindolo: Protocol/project development, Data collection or management, Manuscript writing/editing. L Schips: Protocol/project development, Data collection or management, Manuscript writing/editing. Conflicts of interest Guido Giusti is a consultant for Boston Scientific, Cook Medical, Porges-Coloplast, Karl Storz. Cesare Mario Scoffone is a consultant for Boston Scientific, Cook Medical, Porges-Coloplast, Karl Storz. F. Berardinelli, L. Cindolo, P. De Francesco, N. Cera, M. Marchioni, S. Proietti, D. Hennessey, O. Dalpiaz, C. Cracco and L. Schips have nothing to disclose. Guarantor F. Berardinelli. Research registration unique identifying number (UIN) researchregistry2275. References [1] S. Chatterji, J. Byles, D. Cutler, T. Seeman, E. Verdes, Health, functioning, and disability in older adultsdpresent status and future implications, Lancet 385 (2015) 563e575, http://dx.doi.org/10.1016/S0140-6736(14)61462-8.
151
[2] H. Hu, Y. Lu, D. He, et al., Comparison of minimally invasive percutaneous nephrolithotomy and exible ureteroscopy for the treatment of intermediate proximal ureteral and renal stones in the elderly, Urolithiasis 44 (2016) 427. [3] D. Prezioso, E. Illiano, G. Piccinocchi, et al., Urolithiasis in Italy: an epidemiological study, Arch. Ital. Urol. Androl. 86 (2014) 99e102. [4] J. Bauer, A. Kahlmeyer, R. Stredele, B.G. Volkmer, Inpatient therapy of urinary stones in Germany: development of the G-DRG system, Urol. A 53 (2014) 1764e1771. [5] A. Sahin, N. Atsu, E. Erdem, et al., Percutaneous nephrolithotomy in patients aged 60 years or older, J. Endourol. 15 (2001) 489e491, http://dx.doi.org/ 10.1089/089277901750299276. [6] F. Berardinelli, S. Proietti, L. Cindolo, A prospective multicenter European study on flexible ureterorenoscopy for the management of renal stone, Int. Braz. J. Urol. 42 (2016) 479e486, http://dx.doi.org/10.1590/S16775538.IBJU.2015.0528. [7] G. Giusti, S. Proietti, L. Villa, et al., Current standard technique for modern flexible ureteroscopy: tips and tricks, Eur. Urol. 70 (2016) 188e194, http:// dx.doi.org/10.1016/j.eururo.2016.03.035. [8] G. Giusti, S. Proietti, R. Peschechera, et al., Sky is no limit for ureteroscopy: extending the indications and special circumstances, World J. Urol. 33 (2015) 257e273. [9] G. Giusti, S. Proietti, L. Cindolo, et al., Is retrograde intrarenal surgery a viable treatment option for renal stones in patients with solitary kidney? World J. Urol. 33 (2015) 309e314. [10] S. De, R. Autorino, F.J. Kim, et al., Percutaneous nephrolithotomy versus retrograde intrarenal surgery: a systematic review and meta-analysis, Eur. Urol. 67 (2014) 125e137, http://dx.doi.org/10.1016/j.eururo.2014.07.003. [11] B.R. Matlaga, J.E. Lingeman, Surgical management of stones: new technology, Adv. Chronic Kidney Dis. 16 (2009) 60e64. [12] D. Dindo, N. Demartines, P.A. Clavien, Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey, Ann. Surg. 240 (2004) 205e213. [13] A. Trinchieri, Epidemiology of urolithiasis: an update, Eur. Urol. 67 (2015) 125. [14] A. Breda, O. Ogunyemi, J.T. Leppert, et al., Flexible ureteroscopy and laser lithotripsy for multiple unilateral intrarenal stones, Eur. Urol. 55 (2009) 1190e1196. [15] Emiliani E, Talso M, Baghdadi M, The use of Apnea during ureteroscopy. Urology doi:10.1016/j.urology.2016.06.016. [Epub ahead of print]. [16] T. Akman, M. Binbay, M. Ugurlu, et al., Outcomes of retrograde intrarenal surgery compared with percutaneous nephrolithotomy in elderly patients with moderate-size kidney stones: a matched-pair analysis, J. Endourol. 26 (2012) 625. [17] F. Berardinelli, L. Cindolo, P. De Francesco, et al., The surgical experience influences the safety of retrograde intrarenal surgery for kidney stones: a propensity score analysis, Urolithiasis (2016) [Epub ahead of print]. [18] F. Berardinelli, P. De Francesco, M. Marchioni, et al., Infective complications after retrograde intrarenal surgery: a new standardized classification system, Int. Urol. Nephrol. 48 (2016) 1757. [19] E. Hermans, P.M. van Schaik, H.A. Prins, et al., Outcome of colonic surgery in elderly patients with colon cancer, J. Oncol. (2010) 865908. [20] S. Kruck, M. Sonnleithner, J. Hennenlotter, et al., Interventional stress in renal stone treatment, J. Endourol. 25 (2011) 1069. [21] P. Kragsbjerg, H. Holmberg, T. Vikerfors, Serum concentrations of interleukin6, tumour necrosis factor-alpha, and C- reactive protein in patients undergoing major operations, Eur. J. Surg. 161 (1995) 17. [22] S.J. Jacobsen, D.J. Jacobson, C.J. Girman, et al., Treatment for benign prostatic hyperplasia among community dwelling men: the Olmsted County study of urinary symptoms and health status, J. Urol. 162 (1999) 1301.