UNCLASSIFIED Post-Operative Acute Urinary Retention After Greenlight Laser. Analysis of Risk Factors from A Multicentric Database Davide Campobasso1, Anna Acampora2, Cosimo De Nunzio3, Francesco Greco4, Michele Marchioni5, Paolo Destefanis6, Vincenzo Altieri4, Franco Bergamaschi7, Giuseppe Fasolis8, Francesco Varvello8, Salvatore Voce9, Fabiano Palmieri9, Claudio Divan10, Gianni Malossini10, Rino Oriti11, Lorenzo Ruggera12, Agostino Tuccio13, Andrea Tubaro3, Giampaolo Delicato14, Antonino Laganà14, Claudio Dadone15, Lugi Pucci16, Maurizio Carrino16, Franco Montefiore17, Stefano Germani18, Roberto Miano18, Salvatore Rabito19, Gaetano De Rienzo20, Antonio Frattini1, Giovanni Ferrari19, Luca Cindolo21. Purpose: Greenlight laser is a mini-invasive technique used to treat Benign Prostatic Obstruction (BPO). Some of the advantages of GreenLight photoselective vaporization (PVP) are shorter catheterization time and hospital stay compared to TURP. Post-operative acute urinary retention (pAUR) leads to patients' discomfort, prolonged hospi- tal stay and increased health care costs. We analyzed risk factors for urinary retention after GreenLight laser PVP. Materials and Methods: In a multicenter experience, we retrospectively analyzed the onset of early and late post-operative acute urinary retention in patients undergoing standard or anatomical PVP. The pre-, intra- and post-operative characteristics were compared betweene patients who started to void and the patients who devel- oped post-operative urinary retention. Results: The study included 434 patients suitable for the study. Post-operative acute urinary retention occurred in 39 (9%). Patients with a lower prostate volume (P < .001), an adenoma volume lower than 40 mL (P < .001), and lower lasing time (P = .013) had a higher probability to develop pAUR at the univariate analysis. The multivar- iate logistic regression confirmed that lower lasing time (95% CI: 0.86-0.99, OR = 0.93, P = .046) and adenoma volume (95% CI: 0.89–0.98, OR = 0.94, P = .006) are correlated to pAUR. Furthermore IPSS ≥ 19 (95% CI: 1.19- 10.75, OR = 2.27, P = .023) and treatment with 5-ARI (95% CI: 1.05-15.03, OR = 3.98, P = .042) are risk factors for pAUR. Conclusion: In our series, post-operative acute urinary retention was related to low adenoma volume and lasing time, pre-operative IPSS ≥ 19 and 5-ARI intake. These data should be considered in deciding the best timing for urethral catheters removal. Keywords: laser; prostatectomy; retention INTRODUCTION GreenLight laser is one of the most versatile and saf-est procedures to treat Benign Prostatic Obstruc- tion (BPO), with the possibility to perform standard 1Dept. of Urology, Ospedale Civile di Guastalla ed Ospedale Ercole Franchini di Montecchio Emilia, Azienda USL-IRCCS di Reggio Emilia, Italy. 2Department of Public Health, Università Cattolica del Sacro Cuore, Rome, Italy. 3Dept of Urology, "Sant'Andrea" Hospital, Sapienza University, Roma, Italy. 4Department of Urology, Humanitas Gavazzeni, Bergamo, Italy. 5Dept. of Medical, Oral and Biotechnological Sciences,“G. D'Annunzio” University of Chieti, Chieti, Italy 6Dept. of Urology, Azienda Ospedaliera Città della Salute e della Scienza di Torino – Sede Molinette, Torino, Italy. 7Dept. of Urology, “Arcispedale Santa Maria Nuova”, Reggio Emilia, Italy. 8Dept. of Urology, “S. Lazzaro” Hospital, Alba, Italy. 9Dept. of Urology, “Santa Maria delle Croci Hospital”, Ravenna, Italy. 10Dept. of Urology, “Rovereto Hospital”, Rovereto, Italy. 11Dept. of Urology, “Ulivella e Glicini Clinic”, Florence, Italy. 12Dept. of Urology, Clinica urologica azienda ospedaliera - University of Padova, Padova, Italy. 13Department of Urology, University of Florence, Unit of Oncologic Minimally-Invasive Urology and Andrology, Careggi Hospital, Florence, Italy. 14Dept. of Urology, “S. Giovanni Evangelista” Hospital, Tivoli, Italy. 15Dept. of Urology, “Santa Croce e Carle” Hospital, Cuneo, Italy. 16Dept. of Urology, AORN “Antonio Cardarelli”, Naples, Italy. 17Dept. of Urology, “San Giacomo” Hospital, Novi Ligure, Italy. 18UOSD Urologia, Fondazione Policlinico Tor Vergata, Rome, Italy. 19Dept. of Urology, “Hesperia Hospital”, Modena, Italy. 20Dept. of Emergency and Organ Transplantation, Urology and Andrology Unit II, University of Bari, Bari, Italy. 21Dept. of Urology, “Villa Stuart” Private Hospital, Rome, Italy.. *Correspondence: Urology Unit - Civil Hospital of Guastalla, Azienda USL-IRCCS di Reggio Emilia, Via Donatori di Sangue 1, Guastalla 42016 (RE), Italy. Phone: +39 0522 837364. Fax: +39 0522 837365.E-mail: d.campobasso@virgilio.it Received September 2020 & Accepted August 2021 vaporization (sPVP), anatomical vaporization (aPVP) or pure enucleation (GreenLEP) (1-3). Which tech- nique should be preferred in terms of outcomes and adverse events is still a matter of debate. In a previ- Urology Journal/Vol 18 No. 6/November-December 2021/ pp. 693-698. [DOI: 10.22037/uj.v18i.6489] ous paper, we showed similar functional results and complication rates after aPVP and sPVP(4). Some of the advantages of GreenLight photoselective vaporiza- tion (PVP) are shorter catheterization time and hospital stay compared to transurethral resection of the prostate (TURP)(5). Post-operative acute urinary retention leads to patients' discomfort, prolonged hospital stay and in- creased health care costs(6). In a recent review, post-op- erative acute urinary retention (pAUR) and clot reten- tion in patients undergoing monopolar o bipolar TURP, GreenLight PVP and Holmium laser enucleation of the prostate (HoLEP) were reported between 0-6% and 0-15.5%, 1-5% and 0-5% and 2-50% and 0-12%, re- spectively(7). Different hypotheses have been postulated to explain this phenomenon, but no clear conclusions or indications have been reached(7-10). Understanding risk factors of post-operative acute urinary retention would allow better tailoring of the procedures and of post-op- erative care. Based on these considerations, we decided to analyze a large multicenter cohort of patients in or- der to evaluate the characteristics of patients developing pAUR and to identify independent risk factors possibly influencing this event in patients with BPO treated by 180W LBO laser. MATERIALS AND METHODS We retrospectively analyzed the onset of early post-op- erative acute urinary retention in patients undergoing standard or anatomical PVP for lower urinary tract symptoms (LUTS) secondary to BPO, in a multi-in- stitutional prospectively collected database, including 20 centers, with one or two experienced surgeons per center, between September 2011 and October 2018 us- ing the 180-W XPS GL system. Post-operative urinary retention was considered as the inability to urinate after the removal of bladder catheter. Expert surgeons per- formed all the procedures. Informed consent was ob- tained from all individual participants included in the study. After the approval of our local ethical committee (protocol number: 1550/2017 SS Annunziata Hospital, "G. D'Annunzio" University of Chieti, Chieti, Italy) a retrospective analysis of the institutional prospective- ly maintained database of all patients who underwent Greenlight laser PVP was performed. Indications to Greenlight PVP was indwelling urinary retention and failure of medical therapies for LUTS. Data were col- lected from patients’ charts and outpatient clinical con- sultations. Inclusion criteria were: availability of data about prostate volume evaluated with trans-rectal ultra- sound (TRUS), lower urinary tract symptoms therapy, pre-operative International Prostate Symptom Score (IPSS), history of catheterization or urinary retention, type of anesthesia (spinal or general), surgical technique (anatomical versus standard PVP), operative time, las- ing time, energy used, energy density, catheterization time and post-operative acute urinary retention. Exclu- sion criteria were: history of prostate cancer, neurogen- ic bladder disease, previous prostate surgery as well as those who underwent GreenLEP or contemporary ure- throtomy, treatment of bladder stones or bladder tumors and conversion to TURP. Antibiotic prophylaxis was administered to all patients according to local protocols. Surgical procedures were performed according to sur- geon’s preferences, as previously described(1,11). In all procedures a cystoscopy to exclude bladder tum- ors was performed, then ureteral orifices and striated sphincter were visualized. In sPVP after the creation of Variables a Overall (n = 434) No pAUR (n = 395) pAUR (n = 39) P Age (years) mean ± SD 68.9 ± 8.3 68.7 ± 8.3 70.0 ± 8.3 .359 Prostate volume (TRUS) (mL) < .001 median [IQR] 55 [43-70] 58.5 [45-74] 45 [35-55] < .001 Adenoma volume (TRUS) (mL) median [IQR] n (%) 36 [25-50] 38 [25-50] 25 [20-35] < 40 ml 238 (54.8%) 206 (52.2%) 32 (82.1%) < .001 > 40 ml 196 (45.2%) 189 (47.8%) 7 (17.9%) BPO/LUTS therapy n (%) None 81 (18.7%) 71 (18.0%) 10 (25.6%) .037 Alpha-blockers 227 (52.3%) 213 (53.9%) 14 (35.9%) 5-ARI 16 (3.7%) 12 (3.0%) 4 ( 10.3%) Combination 110 (25.3%) 99 (25.1%) 11 (28.2%) Phytotherapy n (%) Yes 59 (13.6%) 56 (14.2%) 3 (7.7%) .260 No 375 (86.4%) 339 (85.8%) 36 (92.3%) Pre-operative IPSS median [IQR] n (%) 23 [19-28] 22 [19-28] 24 [21-28] .132 < 19 93 (21.4%) 89 (22.5%) 4 (10.3%) .075 ≥ 19 341 (78.6%) 306 (77.5%) 35 (89.7%) Indwelling catheter history n (%) Yes 62 (14.3%) 59 (14.9%) 3 (7.7%) .217 No 372 (85.7%) 336 (85.1%) 36 (92.3%) Post-operative Catheterization time (days) median [IQR] 2 [1-3] 2 [1-3] 1 [1-3] .248 Anesthesia n (%) Spinal 402 (92.6%) 365 (92.4%) 37 (94.9%) .574 General 32 (7.4%) 30 (7.6%) 2 (5.1%) Surgical technique n (%) Standard PVP 243 (56.0%) 219 (55.4%) 24 (61.5%) .464 Anatomic PVP 191 (44.0%) 175 (44.6%) 15 (38.5%) Energy used (kJ) median [IQR] 210[152.178-304.594] 214.45[153.11-315] 190[149.64-246.04] .148 Energy density (kJ/mL) median [IQR] 4.1 [2.6-5.3] 4.1 [2.5-5.4] 4.1 [3.2-5.2] .573 Operative time (min) median [IQR] 52 [40-70] 52 [40-70] 52 [35-60] .314 Lasing time (min) median [IQR] 24.6 [18-35] 25 [18-35.1] 20 [16-26] .013 Table 1. Patients’s pre-, intra- and post-operative characteristics stratified according acute urinary retention incidence. aTable values are n (%), mean ± SD or median [IQR]. Abbreviations: TRUS, trans-rectal ultrasound; BPO, Benign Prostatic Obstruction; LUTS, lower urinary tract symptoms; IPSS, Interna- tional Prostate Symptom Score; pAUR, post-operative acute urinary retention. Predicting Factors of Post-Operative Acute Urinary Retention After Greenlight Laser-Campobasso et al. Unclassified 694 Vol 18 No 6 November-December 2021 695 a working space at 5 and 7 o’clock, the prostate was vaporized in circumferential manner from the prostat- ic urethra towards the prostatic capsule (inside out). Differently, in aPVP after vaporization of the adeno- ma at the apex up to the localization of the capsule, the surgeon carried out a bilateral incision lateral to veru- montanum and using the tip of resectoscope performes a mechanical dissection of the tissue. The dissection plane is followed towards the bladder neck at 6 o’clock and during the dissection the tissue is vaporized, which is obtained by firing the laser towards prostatic urethra (outside in). Depending on the center, a 24.5-Ch (Rich- ard Wolf, Germany) or 26-Ch (Karl Storz, Germany) resectoscope with a laser bridge were used. In both techniques, all the tissues were vaporized and morcella- tion was not necessary. Considered pre-operative variables were: prostate vol- ume, drugs treatment for LUTS, IPSS, the presence of indwelling bladder catheter. Intra-operative variables were: type of anesthesia, operative time, lasing time, energy used, energy density and surgical technique. The post-operative variable was catheterization time and the incidence of early and late (at 90 post-operative days) urinary retention. Statistical analysis Descriptive analyses were performed for total sample and according to the reporting of post-operative AUR, calculating means and standard deviations (SD) of nor- mally distributed continuous variables, such as age, based on their distribution (assessed using Shapiro– Wilk test) and median and interquartile range (IQR) for non-normal variable (e.g. adenoma volume, energy and irradiation time). Frequencies and related percentages were reported to synthesize categorical variables. Uni- variate analyses, aimed at identifying factors potential- ly associated with the development of post-operative AUR, were carried-out using chi square test for com- paring categorical variables and using t Student test or Mann-Whitney test for numeric continuous variables as appropriate. The normality of these variables was test- ed using the Shapiro Wilk test. Factors showing a P < .200 at univariate analysis were, therefore, included in the multivariate analysis and a logistic regression was performed. RESULTS The multicenter database included 434 patients suita- ble for the study. Post-operative acute urinary retention occurred in 39 patients (9%). All the cases of pAUR occurred due to the inability to void after bladder cathe- ter removal, in the absence of bleeding or retention due to clots or hemorrhage. Patients who developed pAUR were treated with application of bladder catheter for 5 days (± 4.5). No further episode of AUR occurred, the patients did not require reintervention or ancillary pro- cedures/exams (urodynamic evaluation) at 90 post-op- erative days. The characteristics of the study population are shown in Table 1. History of preoperative urinary retention in the pAUR and no pAUR groups was 7.7% and 14.9%, respectively (P = .217). Referring to pre-op- erative variables, a lower prostate volume was present in patients who developed pAUR (45 mL, IQR 35-55 versus 58.5 mL, IQR 45-74, P < .001). Patients with an adenoma volume less than 40 mL had a higher proba- bility to develop pAUR at univariate analysis (82.1%, P < .001) and the type of the pre-operative medical treatment for BPO was linked to the risk of failure of early catheter removal after surgery. On the contrary, the incidence of pAUR was not affected by age, IPSS score and indwelling catheter history (Table 1). How- ever, in patients with an IPSS score ≥ 19 the P was equal to .075, suggesting an increased occurrence of pAUR. The multivariate logistic regression showed that an IPSS ≥ 19 was associated with higher proba- bility to develop postoperative AUR (95% CI: 1.19- 10.75, OR = 2.27, P = .023). Analyzing intra-operative findings at the univariate analysis, surgical techniques (standard or anatomical PVP), operative time, energy used and density and type of anesthesia (general or spinal) did not differ between the two groups (Table 1). Interestingly, at the univariate analysis lower lasing time correlated to the incidence of pAUR (P = .013). This datum received a borderline confirmation at the multivariate logistic regression analysis with an OR of 0.94 (0.88–1.00). Age-adjusted logistic regression showed that the higher was the adenoma volume the lower was the probability to develop a post-operative AUR. Furthermore, an increase in adenoma volume of 1 mL was associated with a decrease of the probability of post-operative AUR of 6% (95% CI: 0.89-0.98, OR = 0.94, P = .006). On the contrary prostate volume was not statistically significant at the multivariate analysis (P = .184), despite its statistical significance at the uni- variate analysis. Moreover, the multivariate logistic re- gression confirmed that energy used during surgery did not influence the incidence of pAUR. In addition, the difference between the two groups in terms of medical treatments have preserved their significance. Patients treated with 5 alpha-reductase inhibitors (5-ARI) re- ported a higher probability of pAUR than those treated with alpha-blockers or no treatments with an OR equal to 3.98 (95% CI: 1.05-15.03, P = .041). The complete multivariate logistic regression analysis of the probabil- ity to develop post-operative AUR are reported in Ta- ble 2. Instead, the two groups did not have a significant difference in term of post-operative catheterization time (P = .248). DISCUSSION TURP is still considered the gold standard for BPO sur- gical treatment. Nevertheless, in the last decade, guide- lines have started to include GreenLight and Holmium laser among BPO treatment options. A recent survey reported how most urologists follow the EAU guide- Predicting Factors of Post-Operative Acute Urinary Retention After Greenlight Laser-Campobasso et al. Table 2. Multivariate logistic regression analysis of the probability to develop post-operative AUR. pAUR Adj OR* 95% CI P Pre-operative IPSS < 19 1 - ≥ 19 2.27 1.19 - 10.75 .023 BPO/LUTS therapy None 1.78 0.72 - 4.41 .212 Alpha-blockers 1 - 5-ARI 3.98 1.05 -15.03 .042 Combination 1.74 0.72 - 4.21 .216 Adenoma volume 0.94 0.89 - 0.98 .006 Prostate volume 1.03 0.99 - 1.07 .184 Energy used (kJ) 1.00 1.00 - 1.00 .138 Lasing time (min) 0.93 0.86 - 0.99 .046 Unclassified 696 lines for LUTS in men with a growing interest in laser procedures(12). One of the advantages of these techno- logical improvements is to perform mini-invasive pro- cedures and the possibility to perform tailored surgery based on patients' characteristics. Laser treatments in BPO ensure the same surgical outcomes of traditional ones with different laser prostatectomy techniques and minor invasiveness(3,5,13-16). Hematuria, post-operative acute urinary retention and urinary tract infections are the three common peri-operative and early complica- tions in prostate surgery for BPO(7,17). Urinary retention after removal of bladder catheter is a cause of patient's dissatisfaction and delay the return to normal activity. In the literature, data on prediction of re-catheterization after endoscopic prostate surgery for BPO are sparse, retrospective and heterogeneous. In patients undergo- ing TURP, catheterization for clot retention is variable between different series (0-15.5%) and is one of the most common causes. Other potential elements for per- sistent obstruction are residual chips of prostatic tissue obstructing the urethra, or underactive bladder(7,8,18). Further factors investigated with discordant results in patients undergoing TURP, HoLEP or GreenLight La- ser PVP were bladder over-distension during surgery, history of diabetes mellitus, age, and several comorbid- ities such as coronary heart disease, renal insufficiency, and Alzheimer’s disease(7,9,10). In the literature GreenLight laser has been reported to have shorter catheterization time compared to TURP (19,20). In this study, we retrospectively analyzed our multicenter experience in order to understand if there are pre-, intra- or post-operative factors that could de- termine a higher risk of pAUR. Several papers demon- strated that chronic urinary retention and age did not have a negative impact on the possibility to resume nor- mal voiding function after catheter removal in patients having GreenLight vaporization(20). In agreement with a previously published articles(21,22), we did not find a statistically significant difference in patients with a his- tory of indwelling catheter and a correlation with age between the two groups (P = .217 and P = .359, re- spectively). Multivariate analysis also confirmed these data. As previously reported, even different surgical techniques (standard versus anatomical PVP) did not influence failure of catheter removal(4). In one of our re- cent papers, where we compared the results of patients undergoing sPVP or aPVP, the median catheterization time was 1 day for both groups with a post-operative acute urinary retention of 8.9 and 9.2% in sPVP and aPVP (P = .872), respectively(4). These data were con- firmed as well in this specific analysis of our series. The type of surgical technique and the post-operative catheterization time did not reach statistical signifi- cance between the two groups (P = .464 and P = .248, respectively). At univariate analysis of our multicenter database, smaller prostate, adenoma volume less than 40 mL and lower lasing time correlate with an increased risk of post-operative catheter removal failure. The importance of adenoma volume and lasing time were confirmed at the logistic regression, while prostate volume was not significant. The presence of smaller adenoma volume in patients with pAUR did not influence further intra-op- erative aspects except the lasing time. In fact, we did not find any difference at the univariate and multivari- ate analyses between the two groups in terms of oper- ative time, energy delivered and density even though the patients who developed pAUR had lower prostate and adenoma volumes (Table 1). These data might be explained by inefficacious vaporization related to in- adequate adenoma removal with excessive energy ab- sorption by the prostatic tissue, which might have an inflammatory and irritating effect. Ineffective tissue removal together with an inflammatory effect might be two factors affecting de novo urinary retention af- ter surgery. In our series, men with a history of severe LUTS may be at risk of pAUR compared to patients with moderate LUTS. This aspect has been never inves- tigated in other reports(9,10,20). Our consideration is due to the correlation between treatment with 5-ARI at the univariate and multivariate analysis and an IPSS score ≥ 19 at the multivariate analysis, with the occurrence of pAUR. In addition, we hypothesize that a pre-exist- ing inflammatory component might influence the rate of pAUR. The pAUR group was composed by men with a lower prostate and adenoma volume, but with a higher rate of 5-ARI assumption in combination or monotherapy (28.2 versus 25.1% and 10.3 versus 3%, respectively) than the no pAUR group. As we know, treatment with 5-ARI should be considered in patients affected by moderate to severe LUTS(23-25). This drug acts by inhibiting cells proliferation and inducing ap- optosis of prostatic epithelial cells. Furthermore, the reduction of expression of Cox-2 and RhoA in the pros- tatic tissue probably attenuate the inflammation process (26). For these reasons, the presence in the pAUR group of a higher rate of assumption of 5ARI in patients with low prostate volume and high IPSS value might be ex- plained by an inflammatory component responsible of the post-operative urinary retention. Obviously, this is a hypothesis needing further investigations. Concerning the operative time, Bae et al(9) previously reported that operative time is a risk factors for pAUR. The authors presumed that the longer operative time caused a pro- longed bladder distension. This over-distension may re- sult in temporary bladder dysfunction. In our series, as well as in the series reported by Kim et al(10), we did not find a correlation between operative time and failure of catheter removal (P = .314). Some limitations are present in this study. First of all it is a retrospective analysis, with a small sample size. The lack of details about the comorbidity profile, pre- operative urodynamic parameters and post void resid- ual urine of our study population may be misleading. Another confounding factor might be the multi-center nature of this study involving several surgeons with not clustered data analyses. In the future, larger prospec- tive studies are needed to better investigate these issues. However, the major strength of our work, in spite of these limitations, is that it is the first study in the litera- ture trying to analyze the risk factors for post-operative catheter removal failure in patients undergoing Green- light laser PVP. CONCLUSIONS In our series, we analyzed pre-, intra- and post-opera- tive factors affecting urinary retention after GreenLight PVP. Low adenoma volume and lasing time, pre-opera- tive IPSS ≥ 19 and 5-ARI intake resulted as risk factors for pAUR. These variables might be analyzed with pro- spective studies to confirm our data and for the timing of catheter removal in this subgroup of patients in order Predicting Factors of Post-Operative Acute Urinary Retention After Greenlight Laser-Campobasso et al. Vol 18 No 6 November-December 2021 697 to better organize hospitalization and recovery. CONFLICT OF INTEREST The Authors declares that there is no conflict of interest REFERENCES 1. Cindolo L, Ruggera L, Destefanis P, Dadone C, Ferrari G. Vaporize, anatomically vaporize or enucleate the prostate? The flexible use of the GreenLight laser. Int Urol Nephrol 2017; 49:405-11. 2. Mordasini L, Moschini M, Mattei A, Iselin C. GreenLight Laser for benign prostatic hyperplasia. Curr Opin Urol 2018; 28:322-8. 3. Barco-Castillo C, Plata M, Zuluaga L, et al. Functional outcomes and safety of GreenLight photovaporization of the prostate in the high- risk patient with lower urinary tract symptoms due to benign prostatic enlargement. 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