Kidney transplantation after pelvic radiotherapy: increased morbidity?

INTRODUCTION: The impact of pelvic irradiation on kidney transplant surgery is still unclear. The main objective of our study is to evaluate the feasibility and the saftety of renal transplantation following pelvic radiotherapy. METHODS: We collected characteristics and kidney transplant data from patients with a history of pelvic cancer treated with pelvic irradiation between 2005 and 2021. These data were collected via the prospective information system "Computerized Data Validated in Transplantation" (DIVAT) and medical records. We carried out a comparative study with a non-irradiated matched control group to compare the data of intraoperative surgeries, complications reported postoperatively as well as survival of the graft and the patient. Patients were matched on age, sex, side of graft implantation, and graft rank. RESULTS: 24 patients were collected with an average age of 65, 18 patients were treated for prostatic adenocarcinoma, 4 for gynecological cancer and 2 testicular cancers. 21 patients were treated by radiotherapy, 3 by brachytherapy. 8 patients had a target dose on the iliac lymph nodes. The comparative study showed a significant difference in operative difficulty (n=15 versus n=1 p<0.01), operative duration (190min versus 149min p=0.005), occurrence of lymphocele (p=0.041). Urinary anastomosis surgical techniques were different, 83.3% of control patients had a ureterovesical anastomosis against 58.3% of patients with a history of irradiation (p=0.057) and about 29% of irradiated patients had an uretero-ureteral anastomosis. There was no other significant difference in per and postoperative criteria or survival. DISCUSSION: A history of pelvic irradiation significantly increases the technical complexity of kidney transplantation without impacting saftey and kidney graft survival.An history of Pelvic irradiation should not be a contraindication to kidney transplant.

Mini-percutaneous nephrolithotomy: Is smaller better for kidney stones in patients with neurogenic bladder?

INTRODUCTION: Patients with neurologic bladder are at an increased risk for urolithiasis, and currently, data on mini-percutaneous nephrolithotomy in this population are limited. Our objective was to compare mini (15F)-percutaneous nephrolithotomy, standard (24F)-PCNL and flexible ureteroscopy in terms of efficacy and safety in treatment of kidney stones in patients with neurogenic lower urinary tract dysfunction (NLUTD). METHODS: We conducted a retrospective monocentric study in our neuro-urological referral centre. All consecutive patients with NLUTD and a cumulative size of renal calculi greater than 15mm or 10mm in the lower calyx, who had extraction surgery between 2005 and 2020, were included. The primary endpoint was the one-session stone-free rate (SFR) at 3 months on a CT scan. The secondary endpoints were complication (Clavien-Dindo grading system), operative time, blood loss and length of hospital stay. RESULTS: We performed 76 standard PCNL (sPCNL), 46 flexible ureteroscopy lithotripsy (fURL) and 25 miniaturized PCNL (mPCNL). The one-session SFR was 37.5% for the mPCNL group, 38.2% for the sPCNL group and 37% for the fURL group with no significant difference between the three procedures (P=0.99). Early complications, blood loss and transfusion rates were lower in the mPCNL group than in the sPCNL group (P=0.047) and comparable to fURL group. The final SFRs after a second intervention for mPCNL, sPCNL and fURL were 48%, 61.8% and 63%, respectively (P=0.67). CONCLUSION: The efficacy of mPCNL in patients with NLUTD was not different from other techniques, but a significantly lower rate of complications than sPCNL was observed. LEVEL OF PROOF: 3.

Switching from onabotulinum toxin A to abobotulinum toxin A for treating detrusor overactivity in spinal cord injured patient, does it really work?

AIM: To assess the efficacy of switching to Abobotulinumtoxin A (ATA) intradetrusor injections (IDI) after failure of Onabotulinumtoxin A (OTA) IDI for the treatment of neurogenic detrusor overactivity in patients with spinal cord injury (SCI). MATERIALS AND METHODS: A single-centre retrospective chart review study. All SCI patients who started OTA IDI after 2011 and had an ATA IDI switch were included. The primary outcome was the clinical and urodynamic efficacy of the switch to ATA IIDs at the last follow-up. Secondary outcomes were initial efficacy, duration of ATA treatment, and patient outcome including the occurrence of augmentation enterocystoplasty at last follow-up. RESULTS: Sixty-two patients were included. Eighteen patients (28.9%) were initially responders to ATA IDI. Nine patients (14.5%) remained responders at last follow-up after a median of 17 months (AE 8.8-29). Thirty-two patients (51.6%) had had or were awaiting augmentation enterocystoplasty with a follow-up time of 18.5 months (IQR 8-27). Eleven patients (17.7%) were on ATA IDI with low efficacy. Seven patients (11.3%) were switched back to OTA and 3 patients (4.8%) changed their voiding pattern. CONCLUSION: Switching from OTA to ATA toxin for IDI in the treatment of detrusor overactivity after spinal cord injury have long-term efficacy for a limited number of patients but may delay the need for surgery.

Robot-assisted radical nephroureterectomy for upper tract urothelial carcinoma: Peri and postoperative outcomes.

INTRODUCTION: The treatment of urothelial tumours of the upper urinary tract at high risk of specific mortality is based on radical nephroureterectomy (RNU). Robotic-assisted laparoscopic radical nephroureterectomy (RARNU) is still under investigation to definitively establish the safety of this procedure in the management of urothelial tumours of the upper urinary tract. The primary objective is to evaluate the intra- and postoperative safety of RARNU and, subsequently, to evaluate the medium-term oncological results. METHODS: Our study is a retrospective, mono-centric study with a collection of RARNUs conducted between 1st January 2015 and 1st October 2021. The RARNUs were performed with the assistance of the Da Vinci Si® robot, then from 2017 the Da Vinci Xi® robot. Whenever possible, the entire procedure was carried out without re-docking. RESULTS: Between 1st January 2015 and 1st October 2021, 29 RARNUs were carried out at our centre. Complete surgery without re-docking was possible in 80% of cases with the Da Vinci Xi® robot. One patient required conversion to open surgery due to difficult dissection. 50% of tumours were classified as T3 or T4. The 30-day complication rate was 31%. The median length of hospitalisation was 5 days. The disease-free survival at the mean survival time (27.5 months) was of 75.2%. One patient had a recurrence in the nephrectomy compartment and no patient had a peritoneal or trocar orifice recurrence. CONCLUSION: Performing RARNU for the management of tumours of the upper urinary tract appears to meet the criteria of surgical safety and those of oncological safety.

[Prostatic hyperplasia: Evaluation of practices in general practice, dissemination, and impact of recommendations]. / L'hypertrophie bénigne de prostate : évaluation des pratiques en médecine générale, diffusion et impact des recommandations.

INTRODUCTION: In 2015, the French Association of Urology, by the male lower urinary tract symptoms Committee, published a practices guideline for the management of prostatic hyperplasia in general practice. Five years after the publication of these recommendation, our objective is to assess their dissemination and their impact in general practice. MATERIAL: A specially designed questionnaire was distributed online via the departmental councils of the order and to all regional unions of liberal doctors. The distribution to general practitioners was at the discretion of each organisation depending on local policies. RESULTS: Two hundred and eighty responses were collected. Fifty-five percent of the population was female. 83 % of the general practitioners did not report having knowledge of the practice guideline. 77 % of doctors stated that they had not received training or information on prostatic hyperplasia in the past 5 years. Among the notable results, 51 % of general practitioners declared performing a digital rectal examination. 44 % prescribed an endorectal ultrasound. Only 7 % of doctors were aware of the existence of minimally invasive surgical techniques. CONCLUSION: The practices guideline for the management of prostatic hyperplasia in general practice proposed in 2015 by the male lower urinary tract symptoms Committee seems to be little known by general practitioners. Dissemination of these recommendations solely through publication in Progrès en Urologie seems ill-suited to consideration by general practitioners, and it seems necessary to consider other modes of dissemination. LEVEL OF EVIDENCE: 4, grade C.

New technique of robot-assisted laparoscopic artificial urinary sphincter implantation in female by a posterior approach with intraoperative cystoscopic monitoring.

PURPOSE: To report the early experience of a modified technique of robot-assisted artificial urinary sphincter (AUS) implantation in female, with a posterior approach to the bladder neck and intraoperative real-time cystoscopic monitoring. METHODS: Retrospective monocentric study included all consecutive female who underwent a primary robot-assisted AUS implantation between 2017 and 2019. Real-time intraoperative cystoscopic monitoring was carried out to check the correct level of the dissection and to avoid any injury during bladder neck dissection. Perioperative and intraoperative data, functional outcomes and complications were assessed. Continence was defined as 0 to 1 pad per day. RESULTS: Twenty-four patients were included, the median age was 66 years, 23/24 (96%) had previous SUI or prolapse surgery. Two conversions to open surgery and 2 modifications of the surgical technique with anterior dissection of the bladder neck were required due to major vesicovaginal adhesions. Overall, 20 patients underwent the robotic posterior approach. Eleven intraoperative complications in 10 patients (50%) occurred, including 7 bladder injuries 4 vaginal injuries, without the need to stop the procedure. The median hospital stay was 3 days (2-7). One AUS was removed at 1 year due to vaginal erosion. At last follow-up (median 26 months (22-36)), 95% of the devices were in place and activated and the continence rate was 84%. CONCLUSIONS: Early functional results of robot-assisted AUS implantation with a posterior approach to the bladder neck and intraoperative cystoscopic monitoring are promising despite the high rate of intraoperative complications due to previous surgeries. Further evaluation of this technique is required.

Perineal recurrence of prostate cancer along a brachytherapy needle track: A case report.

Metastatic recurrence in an atypical site, such as the perineum, can occur after prostatectomy, cryotherapy, or brachytherapy, but is uncommon. To our knowledge, this is only the third case of perineal recurrence of prostatic cancer along a low dose rate brachytherapy needle track. A 64-year-old man was referred to an urologist with an increased PSA of 6.9ng/mL in December 2008. There were no urinary symptoms. Prostatic biopsies revealed a Gleason 6 adenocarcinoma (3+3), and he was treated with low dose rate brachytherapy in May 2009. Sixty-seven seeds of iodine 125 were loaded under ultrasound control, and the PSA subsequently fell to a nadir of 1.19ng/mL in November 2015. Eight years (May 2017) after the initial treatment, the PSA rose to 5.2ng/mL. Pelvic MRI and choline PET revealed a nodule in the region of the left internal obturator muscle. Nodule biopsies confirmed prostatic origin. This perineal recurrence is thus most likely related to seeding of tumour cells along the track of a brachytherapy needle. To our knowledge, this is only the fourth case of perineal recurrence of prostatic cancer along a low-dose rate brachytherapy needle track. Perineal recurrence of prostatic cancer along a LDR brachytherapy needle track can occur. Improved imaging techniques may help to identify this type of recurrence earlier and optimise treatment.

[Acute renal failure of the donor in encephalic death: A real contraindication to kidney transplantation?] / L'insuffisance rénale aiguë du donneur en mort encéphalique : une réelle contre-indication à la transplantation rénale ?

INTRODUCTION: The shortage of kidney transplants encourages the expansion of the limits of eligibility criteria for donation. Many donors who are brain dead display acute renal failure at the time of death; is this a real contraindication to harvesting? The aim of this study was to assess kidney graft survival from donors after brain death with confirmed acute renal failure, with or without anuria previous donation. MATERIALS AND METHODS: All of the transplants performed in two university hospitals between 2010 and 2017 were analyzed retrospectively. All patients who underwent single kidney transplant from a brain-dead donor with acute renal failure (ARF) were included in this study. ARI was defined here by a decrease over 50 % of glomerular filtration rate (GFR) to a threshold below 45mL/min/1.73 m2 at the time of kidney procurement. Kidney graft survival, incidence of delayed graft function (DGF) and the GFR at 12 months were analyzed. Analysis of kidney transplant survival based on pre-implantation biopsies was additionally done. RESULTS: One hundred and sixty four patients were transplanted with a kidney from donor with ARF during the selected period. At the admission in ICU the average GFR was 67,7±19mL/min/1,73m2. At the time of donation, the average age of donors was 56.4±17.7 years, the GFR was 33.7±8.0mL/min/1.73 m2 16 % of donors were anuric. Cold ischemia time (CIT) was 16.8±5.0hours. The average age of recipients was 55.6±14.1 years. 81 % of the cases were primary transplants. Graft function took place within 7.8±9.4 days after transplantation. There were two non-primary functions (PNF). One hundred and fifty two patients (93 %) had a functional graft at 12 months. The mean GFR at 12 months was 46.8±20.1mL/min/1.73 m2 and 122 patients (73 %) had a GFR greater than 30mL/min/1.73 m2. Seventy-one percent of preimplantation biopsies revealed acute tubular necrosis (ATU); no cortical necrosis was observed. Survival of theses grafts was 85 %, comparable to the total population of study (P=0,21) CONCLUSION: The acute renal failure of the brain-dead donor should not alone be systematically a contraindication to harvesting and kidney transplantation.

Ileal ureter replacement: Early morbidity and long-term results.

INTRODUCTION: Ileal ureter is a technique that consists of replacing the ureter by a segment of ileum to treat a long ureteric lesion or a lesion involving the lumbar ureter. The primary objective of our study was to assess the early perioperative morbidity of ileal ureter according to the Clavien-Dindo classification. The secondary objectives were to assess the morbidity and the medium- and long-term outcome of renal function. MATERIALS AND METHODS: Single-centre retrospective study, collecting data from patients operated between February 2005 and October 2019. All patients who underwent ileal ureter replacement surgery in our unit were included in this analysis. The ureteric defect was longer than five centimetres and involved the pelvic and/or iliac and/or lumbar ureter. All ileal ureter replacements were performed by open surgery using isoperistaltic ileal grafts. RESULTS: Twenty-one patients (11 women and 10 men) underwent total or subtotal, unilateral or bilateral ileal ureter replacement, corresponding to 25 kidneys. The grade III early postoperative complication rate was 9.5% (two cases) mainly consisting of bleeding. No grade IV or V complications were observed. With a mean follow-up of 85 months, long-term morbidity essentially consisted of infectious complications. No patients developed anastomotic strictures. Mean serum creatinine was 116.3µmol/L preoperatively, 105.6µmol/L one month postoperatively and 112.2µmol/L at last follow-up. Renal function was generally preserved or even improved, except for patients with preoperative renal failure. CONCLUSION: Ileal ureter replacement is a surgical alternative associated with low morbidity and satisfactory long-term functional results. LEVEL OF EVIDENCE: 3.

Feasibility and safety of laparoscopic living donor nephrectomy in case of right kidney and multiple-renal artery kidney: a systematic review of the literature.

PURPOSE: To access the current status of the security and feasibility of right kidney (RK) and multiple-renal artery (MRA) laparoscopic living donor nephrectomy (LLDN) which are more challenging compared to left kidney (LK) and single renal artery (SRA) because of a shorter renal vein and more complex vascular anatomy. METHODS: We did a systematic review of the literature according to the PRISMA recommendations, reporting RK or MRA donor nephrectomy performed with a laparoscopic technique compared to LK or SRA kidney LLDN. The identified and analyzed primary outcomes of interest were operating time (OT), warm ischemia time (WIT), rate of conversion and transfusion, donor length of stay (LOS), delayed graft function (DGF) and rate of graft loss (GL). RESULTS: 16 comparative studies (1397 cases) of RK-LLDN and 12 comparative studies including 15 series (993 cases) of MRA-LLDN were selected. For RK-LLDN review, conversion rate was 0.8% and blood transfusion rate 0.2%, only one case of graft venous thrombosis was reported, OT was shorter in four studies and there was no any difference of DGF and GL rate compared to LK-LLDN. For MRA-LLDN review, conversion rate was 1.3% and blood transfusion rate 1.1%, OT and WIT were longer compared to SRA-LLDN, there were more ureteral complications in two studies, and no difference in terms of vascular complications and graft loss rate. CONCLUSION: RK-LLDN and MRA-LLDN would be similar to LK-LLDN and SRA-LLDN in terms of feasibility and safety for the donor as well as graft function results for RK-LLDN.

[Renal transplantation on vascular prosthesis]. / Transplantation rénale sur prothèse vasculaire.

INTRODUCTION: In front of a very calcified aortoiliac axis, renal transplantation with implantation of the artery on vascular prosthesis can be proposed. This rare intervention is considered difficult and morbid. The main objective of this work was to evaluate the overall and specific survival of the transplant in this situation. The secondary objective was the study of the complications and the evolution of the transplant's renal function. MATERIAL AND METHODS: From a multicenter retrospective data collection of the DIVAT cohort (6 centers) added with data from 4 other transplant centers, we studied transplants with prosthetic arterial anastomosis. RESULTS: Thirty four patients was included. The median duration of follow-up was 2.5 years. 4 patients died in the month following transplantation, 16 were hemodialysis and 9 were transfused. The median survival of the transplant was 212 days. Functional arrests of the transplant were mostly associated with nephrological degradation and return to dialysis (about 80%) while 10% were related to a death of the recipient directly attributable to renal transplantation. The surgical complications of the transplantation were marked by one arterial stenosis, one fistula and 4 urinary stenoses. CONCLUSION: Thus, renal transplantation with arterial anastomosis on vascular prosthesis, on selected patients, offers an alternative to dialysis. A national compendium of transplanted patients on vascular prosthesis would allow a long-term follow-up of transplant's survival and define selection criteria prior to this kind of surgery. LEVEL OF EVIDENCE: 3.

Transplant nephrectomy after graft failure: is it so risky? Impact on morbidity, mortality and alloimmunization.

PURPOSE: To determine the impact of transplant nephrectomy on morbidity and mortality and HLA immunization. METHODS: All patients who underwent transplant nephrectomy in our centre between 2000 and 2016 were included in this study. A total of 2822 renal transplantations and 180 transplant nephrectomies were performed during this period. RESULTS: The indications for transplant nephrectomy were graft intolerance syndrome: 47.2%, sepsis: 22.2%, vascular thrombosis: 15.5%, tumour: 8.3% and other 6.8%. Transplant nephrectomies were performed via an intracapsular approach in 61.7% of cases. The blood transfusion rate was 50%, the morbidity rate was 38% and the mortality rate was 3%. Transplant nephrectomies more than 12 months after renal transplant failure were associated with more complications (p = 0.006). Transfusions in the context of transplant nephrectomy had no significant impact on alloimmunization. CONCLUSION: The risk of bleeding, and therefore of transfusion, constitutes the major challenge of this surgery in patients eligible for retransplantation. Even if transfusions in this context of transplant nephrectomy had no significant impact on alloimmunization, this high-risk surgery, whenever possible, must be performed electively in a well-prepared patient.

[Bladder cancer in neurogenic patients: A retrospective study of management and follow-up]. / Cancers de vessie chez les patients neurologiques : étude rétrospective de prise en charge et de suivi.

INTRODUCTION: The prevalence of bladder cancer (BC) in neurological patients seems to be similar to that of the general population. However, they are more aggressive with a higher rate of muscle-invasive forms and squamous cells carcinomas. The aim of the current study was to report etiologies, management and outcomes of BC in neurological population. MATERIAL AND METHOD: Were enrolled all neurological patients with a BC diagnosed between 2004 and 2017. The following data were retrospectively reported: age, gender, duration of the disease, mode of discovery, histological type, treatment and outcomes. RESULTS: In total, 27 patients were included: 11 spinal cord injuries, 7 Parkinson's disease, 5 multiple sclerosis, 3 head trauma, 3 brain strokes, 2 cerebral palsies and 1 spina bifida. The histological subtypes were as follows: 22 transitional cells carcinomas, 4 squamous cell carcinomas (SCC), one mucinous adenocarcinoma, one sarcomatoid and one neuroendocrine with 19 high-grade tumors and 15 muscle-invasive bladder cancer. Seven patients (26%) were diagnosed before 15 years history of neurogenic bladder. The mean follow-up was 14 months (1-210 months). Eight deaths were observed, with 5 related to bladder cancer. In our study, smoking habits, voiding mode, lithiasis or infection histories were not related with a more aggressive pattern, such as SCC. CONCLUSION: The high rate of muscle-invasive bladder cancer and aggressive patterns justify neuro-urological follow-up, even before 15 years of neurogenic bladder. LEVEL OF EVIDENCE: 4.

[Long-term outcomes of prostate cancer patients with lymph nodes metastasis after radical prostatectomy and pelvic lymph node dissection]. / Résultats oncologiques à long terme des patients ayant un cancer de la prostate traité par prostatectomie totale et curage ganglionnaire avec atteinte métastatique ganglionnaire infraclinique.

INTRODUCTION: The aim of this study was to evaluate biochemical recurrence-free survival (RFS) and to identify useful predictors of such survival in localized prostate cancer patients (cN0) and pelvic lymph node metastasis (pN+) treated with radical prostatectomy and pelvic lymph node dissection. PATIENTS AND METHODS: This multicenter and retrospective study, assessed overall survival (OS), cancer specific survival (CSS) and biochemical recurrence-free survival (RFS), between January 2005 until December 2010 with 5 years of distance. We evaluated factors predicting long-term RFS in node positive prostate cancer patients. RESULTS: Thus, 30 patients were included. Median follow-up was 89.9±27.4 months. After surgery, patients were treated with surveillance (n=4, 13.5%), adjuvant hormone therapy (n=22, 73%) or combination of radio and hormone therapy, (n=4, 13.5%). During the follow-up, 50% of patients had biochemical recurrence, with a mean time period of 38±30 months. Five and 10-year RFS were 57% and 41% respectively. Extra lymph nodes extension (P=0.00021) and pathological margin status (P=0.0065) were independent predictors of 5-year RFS. CONCLUSION: Biochemical RFS of patients treated with radical prostatectomy and subclinical lymph node metastatic disease is adequate and multifactorial. However, this study identifies pathological margin status and extra lymph node extension as independent factors of b RFS. LEVEL OF EVIDENCE: 4.

[Analysis of success rates of uretroplasty for adult male bulbar urethral stricture: A systematic review]. / Analyse des taux de succès des urétroplasties pour sténoses de l'urètre bulbaire chez l'homme adulte : revue systématique de la littérature.

Male urethral stricture disease is prevalent and has an important impact on quality of life. Direct visual urethrotomy and dilatations have high rates of recurrence. OBJECTIVES: The aim of this review of literature was to evaluate the success rates of different techniques of urethroplasty for strictures of the bulbar urethra. METHODS: We performed a systematic review of the MEDLINE literature from 2004 to 2015 following the PRISMA's statement recommendations. Key words were: urethroplasty, urethral reconstruction, onlay, graft, urethral stricture. Inclusion criteria were original articles describing the results of urethroplasty for bulbar urethral stricture in an adult male population. A minimum follow-up of 24 months was required. RESULTS: From 891 articles of the literature, 20 are studied in this review. Only 3 studies were prospective. The success rate of anastomotic urethroplasty varied from 68.7 to 98.8% for strictures from 1 to 3.5cm, from 60 to 96.9% for augmented urethroplasty performed for strictures from 4.2 to 4.7cm. Substitution urethroplasty with grafts presented from 75 to 89.8% of success for strictures from 2.6 and 4.36cm. Overall, 19/20 studies used buccal mucosal graft. CONCLUSION: The success rate of urethroplasty for bulbar urethral stricture is high; the surgical technique should be adapted to the length of the stricture.

[Ischemia is not an independent predictive factor of chronic renal failure after partial nephrectomy in a solitary kidney in patients without pre-operative renal insufficiency]. / L'ischémie a un impact limité sur la fonction rénale après néphrectomie partielle sur rein unique chez les patients sans insuffisance rénale préopératoire.

OBJECTIVE: To assess the influence of vascular clamping and ischemia time on long-term post-operative renal function following partial nephrectomy (PN) for cancer in a solitary kidney. PATIENTS AND METHODS: This is a retrospective study including 259 patients managed by PN between 1979 and 2010 in 13 centers. Clamping use, technique choice (pedicular or parenchymal clamping), ischemia time, and peri-operative data were collected. Pre-operative and last follow-up glomerular filtration rates were compared. A multivariate analysis using a Cox model was performed to assess the impact of ischemia on post-operative chronic renal failure risk. RESULTS: Mean tumor size was 4.0±2.3cm and mean pre-operative glomerular filtration rate was 60.8±18.9mL/min. One hundred and six patients were managed with warm ischemia (40.9%) and 53 patients with cold ischemia (20.5%). Thirty patients (11.6%) have had a chronic kidney disease. In multivariate analysis, neither vascular clamping (P=0.44) nor warm ischemia time (P=0.1) were associated with a pejorative evolution of renal function. Pre-operative glomerular filtration rate (P<0.0001) and blood loss volume (P=0.02) were significant independent predictive factors of long-term renal failure. CONCLUSION: Renal function following PN in a solitary kidney seems to depend on non-reversible factors such as pre-operative glomerular filtration rate. Our findings minimize the role of vascular clamping and ischemia time, which were not significantly associated with chronic renal failure risk in our study. LEVEL OF EVIDENCE: 5.