Photodynamic diagnostic ureterorenoscopy with orally administered 5-aminolaevulinic acid as photosensitiser: how I do it.

OBJECTIVE: To explain our use of photodynamic diagnostic ureterorenoscopy, we provide a detailed description of the choice of photosensitiser, equipment needed, a safety profile, and pointers on our technique. TECHNIQUE: Patients are given oral 5-aminolaevulinic acid (5-ALA) as a photosensitiser 3-4 h pre-operatively, and by using a Xenon blue light source, an eyepiece which blocks light below 450 nm which is fitted onto the ureterorenoscope, we are able to conduct a thorough photodiagnosis of the upper urinary tract. CONCLUSION: Our technique of photodynamic diagnostic ureterorenoscopy has shown that the sensitivity, specificity and detection rates of upper urinary tract lesions can be significantly increased with the use of oral 5-ALA. Therefore, we provide a detailed explanation of the use of oral 5-ALA photosensitiser, indications and contraindications of the technique in addition to equipment used and potential complications of the procedures.

Extracorporeal shock wave lithotripsy (ESWL) versus ureteroscopic management for ureteric calculi.

BACKGROUND: Ureteral stones frequently cause renal colic, and if left untreated, can lead to obstructive uropathy. Extracorporeal shock wave lithotripsy (ESWL) and ureteroscopy, with or without intracorporeal lithotripsy, are the most common interventions used to treat ureteral stones. ESWL treatment is less invasive than ureteroscopy, but has some limitations such as a high retreatment rate, and is not available in all centres. Recent advances in ureteroscopy have increased success rates and reduced complication rates. OBJECTIVES: To examine evidence from randomised controlled trials (RCTs) on the outcomes of ESWL or ureteroscopy in the treatment of ureteric calculi. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL in The Cochrane Library Issue 2, 2011), MEDLINE (1966 to March 2011), EMBASE (1980 to March 2011), CINAHL, Clinicaltrials.gov, Google Scholar, reference lists of articles and abstracts from conference proceedings, all without language restriction. SELECTION CRITERIA: RCTs that compared ESWL with ureteroscopic retrieval of ureteric stones were included in this review. Study participants were adults with ureteric stones requiring intervention. Published and unpublished sources were considered for inclusion. DATA COLLECTION AND ANALYSIS: Three authors independently assessed study quality, risk of bias, and extracted data. Statistical analyses were performed using the random-effects model. Results were expressed as risk ratios (RR) for dichotomous outcomes or mean differences (MD) for continuous data, both with 95% confidence intervals (CI). MAIN RESULTS: Seven RCTs (1205 patients) were included in the review. Stone-free rates were lower in patients who underwent ESWL (7 studies, 1205 participants: RR 0.84, 95% CI 0.73 to 0.96) but re-treatment rates were lower in ureteroscopy patients (6 studies, 1049 participants: RR 6.18, 95% CI 3.68 to 10.38. ESWL-treated patients had less need for auxiliary treatment (5 studies, 751 participants: RR 0.43, 95% CI 0.25 to 0.74; fewer complications (7 studies, 1205 participants: RR 0.54, 95% CI 0.33 to 0.88); and shorter length of hospital stay (2 studies, 198 participants: MD -2.55 days, 95% CI -3.24 to -1.86).Three studies adequately described the randomisation sequence, three studies were unclear on how they randomised, while one study had a high risk of selection bias. All the studies had an unclear risk of performance bias and detection bias, while all had a low risk of attrition bias, reporting bias, or other sources of bias identified. AUTHORS' CONCLUSIONS: Compared with ESWL, ureteroscopic removal of ureteral stones achieves a greater stone-free state, but with a higher complication rate and longer hospital stay.

Extracorporeal shock wave lithotripsy (ESWL) versus ureteroscopic management for ureteric calculi.

BACKGROUND: Ureteral stones frequently cause renal colic, and if left untreated, can lead to obstructive uropathy. Extracorporeal shock wave lithotripsy (ESWL) and ureteroscopy, with or without intracorporeal lithotripsy, are the most common interventions used to treat ureteral stones. ESWL treatment is less invasive than ureteroscopy, but has some limitations such as a high retreatment rate, and is not available in all centres. Recent advances in ureteroscopy have increased success rates and reduced complication rates. OBJECTIVES: To examine evidence from randomised controlled trials (RCTs) on the outcomes of ESWL or ureteroscopy in the treatment of ureteric calculi. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL in The Cochrane Library Issue 2, 2011), MEDLINE (1966 to March 2011), EMBASE (1980 to March 2011), CINAHL, Clinicaltrials.gov, Google Scholar, reference lists of articles and abstracts from conference proceedings, all without language restriction. SELECTION CRITERIA: RCTs that compared ESWL with ureteroscopic retrieval of ureteric stones were included in this review. Study participants were adults with ureteric stones requiring intervention. Published and unpublished sources were considered for inclusion. DATA COLLECTION AND ANALYSIS: Three authors independently assessed study quality, risk of bias, and extracted data. Statistical analyses were performed using the random-effects model. Results were expressed as risk ratios (RR) for dichotomous outcomes or mean differences (MD) for continuous data, both with 95% confidence intervals (CI). MAIN RESULTS: Seven RCTs (1205 patients) were included in the review. Stone-free rates were lower in patients who underwent ESWL (7 studies, 1205 participants: RR 0.84, 95% CI 0.73 to 0.96) but re-treatment rates were lower in ureteroscopy patients (6 studies, 1049 participants: RR 6.18, 95% CI 3.68 to 10.38. ESWL-treated patients had less need for auxiliary treatment (5 studies, 751 participants: RR 0.43, 95% CI 0.25 to 0.74; fewer complications (7 studies, 1205 participants: RR 0.54, 95% CI 0.33 to 0.88); and shorter length of hospital stay (2 studies, 198 participants: MD -2.55 days, 95% CI -3.24 to -1.86).Three studies adequately described the randomisation sequence, three studies were unclear on how they randomised, while one study had a high risk of selection bias. All the studies had an unclear risk of performance bias and detection bias, while all had a low risk of attrition bias, reporting bias, or other sources of bias identified. AUTHORS' CONCLUSIONS: Compared with ESWL, ureteroscopic removal of ureteral stones achieves a greater stone-free state, but with a higher complication rate and longer hospital stay.

Ureterorenoscopy training on cadavers embalmed by Thiel's method: simulation or a further step towards reality? Initial report.

INTRODUCTION: The technique of ureterorenoscopy has a significant learning curve. Cadavers embalmed by the Thiel method have been successfully used for simulation training in a number of surgical specialties. Here we present our experience of the first use of Thiel cadavers in a formal ureteroscopy training course. MATERIAL AND METHODS: The inaugural 'Masterclass in Flexible Ureterorenoscopy' was run with participants performing ureterorenoscopy on three Thiel cadavers under expert supervision. A qualitative questionnaire was delivered to the participants and faculty. Assessed domains were tissue characteristics of the cadaveric urinary tract, anatomical features and procedural aspects. A five-point Likert score was used to assess responses. Data regarding participant experience in endourology were also collected. RESULTS: 8 questionnaires were collected. All participants completed cadaveric ureterorenoscopy. Three-quarters reported the overall quality of tissue in the cadaveric bladder, ureters and pelvicalyceal system as high or excellent. Half reported the cadaveric bladder as being softer than in a live patient, whilst five out of eight thought that the cadaveric ureter was softer and more prone to trauma. Seven out of eight were satisfied with the overall quality of the cadaveric model. The quality of vision and irrigation in the upper urinary tracts was reported as high. CONCLUSIONS: Thiel cadavers have been shown to have excellent tissue characteristics, as well as being durable and reusable. We have described the first use of Thiel cadavers in a designated ureterorenoscopy course, with high levels of delegate satisfaction. Further work is required to develop the role of Thiel cadavers as part of an integrated, modular urology training.

Are we closer to seeing carcinoma in situ in the upper urinary tract?

INTRODUCTION: There is observed increase in detection rate of upper urinary tract urothelial cancer worldwide. This is a result of improved imaging as well as implementation of novel technologies of direct visualization of upper urinary tract. Standard techniques still remain insufficient to diagnose flat urothelial lesions. Carcinoma in situ is characterized by flat disordered proliferation of urothelial cells with marked cytologic abnormality, which occur within one cell layer as well as full thickness urothelium and therefore requires a better technology to pick up early and subtle mucosal changes. MATERIAL AND METHODS: The review presents available diagnostic tools in detection of upper urinary tract urothelial cancer and their ability to depict carcinoma in situ. RESULTS: Ureterorenoscopy is an investigation of choice as various promising techniques are under pilot investigations to enhance visualization of upper urinary tract carcinoma in situ. So far only photodynamic diagnosis has been reported to be as effective in detection of carcinoma in situ in the upper as within the lower urinary tract. CONCLUSIONS: Although we are close to see upper urinary tract carcinoma in situ all new promising diagnostic techniques still require further validation in multicenter clinical trials to indicate any change to current recommendations.

Concurrent bladder cancer in patients undergoing photodynamic diagnostic ureterorenoscopy: how many lesions do we miss under white light cystoscopy?

INTRODUCTION: There is an ongoing debate on panurothelial changes in the upper and lower urinary tract as multifocal presentation of urothelial cancer is well recognised. Concurrent bladder cancer impacts the outcome of the upper urinary tract urothelial cancer treatment, while its detection still relies on the white light cystoscopy. MATERIAL AND METHODS: We retrospectively reviewed all patients who underwent photodynamic diagnostic ureterorenoscopy, choosing those who had synchronous bladder biopsies. Each patient received 20 mg/kg body weight of oral 5-Aminolevulinic acid around 3-4 hours before endoscopy. All procedures were performed by a single endourologist experienced in photodynamic diagnosis and flexible ureterorenoscopy. RESULTS: Between July 2009 and June 2013, 69 patients underwent bladder biopsies at the time of photodynamic diagnostic endoscopic inspection of the upper urinary tract. In total, 43.5% (30/69) patients were found to have bladder lesions, of which 43.3% (13/30) were proven to be carcinoma in situ. White light inspection of the bladder missed bladder cancer in 16 (23.1%) patients, of which 12 were carcinoma in situ. There were 14 bladder cancer lesions missed under white light which were concomitant to the upper urinary tract urothelial cancer. Twelve (17.4%) patients developed minor complications relevant to the photosensitizer. CONCLUSIONS: The study raises a concern about missing small bladder cancer/carcinoma in situ lesions on the initial diagnosis or in surveillance of the upper urinary tract urothelial cancer. Higher than previously reported, the rate of concomitant bladder cancer may suggest utilisation of photodynamic diagnosis to ensure the cancer free status of the bladder, but this needs to be ratified in a multi-institutional randomised trial.

Photodynamic diagnostic ureterorenoscopy: A valuable tool in the detection of upper urinary tract tumour.

BACKGROUND: Photodynamic diagnosis increases the detection rate and hence decreases recurrence rates of urothelial cancer (UC) of the bladder. This technique has been implemented in the upper urinary tract and like in the bladder, has shown to increase the detection rate of urothelial lesions. OBJECTIVES: To determine the sensitivity, specificity, and detection rates for photodynamic diagnostic flexible ureterorenoscopy (PDD-FURS) and white light ureterorenoscopy (WL-FURS). Design between 2009 and 2013, PDD-FURS was performed within 106 Upper urinary tract (UUT) Units (Mean age-72.6±9.5). Indications for the procedure included abnormal upper urinary tract on imaging, normal flexible cystoscopy with abnormal urine cytology, endoscopic treatment and follow-up of UUT UC. Oral 5-aminolevulinic acid was used as the photosensitizer administered 3-4 h pre-operatively. RESULTS: 48 lesions were detected, of which 95.8% (46/48) where visualised by PDD-FURS compared to 47.9% (23/48) shown by WL-FURS (P<0.0001). PDD-FURS detected significantly more carcinoma in situ (CIS) or dysplasia lesions than WL-FURS (93.75% (15/16) vs. 18.75% (3/16), respectively, (P=0.0006)). Furthermore, PDD-FURS detected significantly more UC lesions than WL-FURS (96.9% (31/32) vs. 62.5% (20/32) (P=0.007)). PDD-FURS was more sensitive (95.8; range: 85.7-99.5) than WL-FURS (53.5; range: 37.7-68.8) in detecting UUT-UC (P<0.0001). There was no difference (P=0.716) in the specificity between PDD-FURS (96.6; range: 88.1-99.6) and WL-FURS (95.2; range: 86.7-99). CONCLUSIONS: Our results PDD-FURS with oral 5-ALA as photosensitizer suggest higher sensitivity and detection rate of urothelial tumours than WL-FURS, with a good safety profile. In our series, PDD-FURS enhanced the visualisation of flat lesions, such as CIS and dysplasia that otherwise would have been missed.

Outcome of ureteroscopy for stone disease in patients with horseshoe kidney: Review of world literature.

INTRODUCTION AND OBJECTIVES: The management of urolithiasis in patients with horseshoe kidney (HSK) is difficult. Stone formation occurred in 1:5 patients with HSK due to impaired urinary drainage and infections. Percutaneous nephrolithotomy and shock wave lithotripsy can be technically challenging due to altered anatomy. MATERIALS AND METHODS: We conducted a systematic review of the literature to look at the role of ureteroscopy for stone management in these patients. We searched MEDLINE, PubMed and the Cochrane Library from January 1990 to April 2013 for results of ureteroscopy and stone treatment in HSK patients. Inclusion criteria were all English language articles reporting on ureteroscopy in patients with HSK. Data were extracted on the outcomes and complications. RESULTS: A total of 3 studies was identified during this period. Forty-one patients with HSK underwent flexible ureteroscopy and stone treatment. The mean age was 42 with a male:female ratio nearly 3:1. The mean stone size was 16 mm (range: 3-35 mm). The mean operating time was 86 min with multiple stones seen in 15 patients. All 41 patients had a ureteral access sheath used and flexible ureteroscopy and holmium laser fragmentation done. Thirty-two (78%) patients were stone-free with a mean hospital stay of 1-day. Minor complications (Clavien I or II) were seen in 13 (32%) of which 6 had stent discomfort, 3 needed intravenous antibiotics for <24 h, 3 had hematuria of which 2 needed blood transfusion and one had pyelonephritis needing re-admission and antibiotics. There were no major complications found in the review. CONCLUSIONS: Retrograde stone treatment using ureteroscopy and lasertripsy in HSK patients can be performed with good stone clearance rate, but with a slightly higher complication rate. This procedure should, therefore, be done in high volume stone center with an experienced stone surgeon/team.

Diagnosis of upper urinary tract tumours: is photodynamic diagnosis assisted ureterorenoscopy required as an addition to modern imaging and ureterorenoscopy?

OBJECTIVES: We aimed to assess the diagnostic accuracy of photodynamic diagnostic ureterorenoscopy (PDD-FURS) in detection of UUT-TCC in comparison with CT Urogram (CTU) and WL-FURS. MATERIAL AND METHODS: Between June 2009 and August 2011, 30 patients underwent PDD-FURS after CTU for suspicion of UUT-TCC. Ureterorenoscopy was performed for abnormal upper urinary tract on imaging. Oral 5-Aminolevulinic Acid (5-ALA) was used as a photosensitizer. All procedures were performed by single endourologist experienced in photodynamic diagnosis. The sensitivity, specificity, and detection rate of WL-FURS, PDD-FURS and CTU were calculated using the Meta-DiSc v1.4 programme. P values <0.05 were considered significant. RESULTS: PDD-FURS detected more UUT-TCCs than CTU or WL-FURS (94% (16/17) vs. 76.5% (13/17) vs. 82% (14/17) respectively). PDD-FURS was not significantly more sensitive than CTU and WL-FURS to detect UUT-TCC (0.94 (95% CI: 0.71-0.99) vs. 0.82 (95% CI: 0.57-0.96) vs. 0.81 (95% CI: 0.54-0.96) respectively; PDD-FURS vs. CTU: P=0.249; PDD-FURS vs. WL-FURS: P=0.277). There was no difference in the specificity between PDD-FURS and WL-FURS (1.0 (95% CI: 0.75-1.0) and 1.0 (95% CI: 0.75-1.0) respectively) (P=1), while PDD-FURS was significantly more specific than CTU (CTU: 0.21 (95% CI: 0.05-0.51) (P<0.001). PDD-FURS picked up 3 cases of CIS, which was not seen on WL-FURL and CTU. CONCLUSION: Oral 5-ALA induced PDD-FURS has a high sensitivity and specificity to detect lesions and a higher detection rate to diagnose UUT-TCC than WL-FURS and CTU. It appears to be the only tool to visualise UUT CIS lesions.

Mitomycin C instillation following ureterorenoscopic laser ablation of upper urinary tract carcinoma.

INTRODUCTION: Instillation of Mitomycin C (MMC) should prevent implantation of cancer cells released during endoscopic treatment and prevent recurrences as seen in carcinoma of the bladder. AIM: TO DEVELOP AND EVALUATE A PROTOCOL FOR A SINGLE DOSE MMC INSTILLATION FOLLOWING HOLMIUM: YAG laser ablation of upper urinary tract transitional cell carcinoma (UUT-TCC). SETTING AND DESIGN: A single institute prospective study. MATERIALS AND METHODS: MMC instillations protocol was designed and offered to patients between August 2005 and April 2011. Following tumor ablation, MMC was instilled into upper urinary tract (UUT) over 40 minutes. All the patients were regularly followed up. RESULTS: Twenty UUT units (19 patients) were managed for UUT-TCCs using our MMC protocol. Two UUT units had G1pTa tumors, 14 had G2pTa, 2 had G3pTa, and 2 had G3pT1. At a mean follow-up of 24 months (range 1-72 months), 13/20 (65%) of the UUT units remained cancer-free, 3 (15%) UUT units developed stricture and were treated with endoscopic dilatation, only 1 (5%) of these developed long-term complications. None of the patients developed postoperative renal impairment or systemic side-effects. CONCLUSIONS: Using a set standard protocol, MMC can safely be instilled into the UUT after TCC ablation with minimal complications or side effects, good preservation of renal function, and with a low recurrences rate comparable to the literature.

Accuracy of photodynamic diagnosis in the detection and follow-up of patients with upper urinary tract lesions: Initial 3-year experience.

OBJECTIVE: To assess the diagnostic accuracy of photodynamic diagnostic (PDD) ureterorenoscopy for detecting upper-urinary tract transitional cell carcinoma (UUT-TCC) in our initial 3 years, and compare the results with that of white light ureterorenoscopy (WLU). PATIENTS AND METHODS: Between August 2007 and March 2010, 32 patients underwent PDD flexible ureterorenoscopy for UUT-TCC. Oral 5-aminolaevulinic acid (5-ALA) was used as the photosensitiser. The sensitivity, specificity and detection rate of PDD were calculated. RESULTS: The sensitivity, specificity, positive and negative predictive values of PDD for detecting abnormal tissue were 96%, 100%, 100% and 88%, compared to the results of WLU of 80%, 86%, 95% and 55%, respectively. PDD was able to detect 96% (24/25) of the abnormal tissue and 96% (21/22) of cancerous tissue, while WLU detected 80% (20/25) of abnormal tissue and 91% (20/22) of the tumour tissue. Three patients of the 32 (10%) developed side-effects related to 5-ALA; two patients developed a facial-skin photosensitive reaction and one developed hypotension. All were treated conservatively, with no long-term effects. CONCLUSION: PDD can be used safely in the UUT, and with a higher sensitivity, specificity and detection rate than standard WLU for detecting UUT tumours.

Flexible ureteroscopy and laser lithotripsy for stones >2 cm: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Urinary stones >2 cm are traditionally managed with percutaneous nephrolithotomy (PCNL). Recently, flexible ureteroscopy and laser lithotripsy) (FURSL) has been used to manage them with comparable results. In a comparative study of renal stones between 2 and 3 cm, FURSL was reported to need less second-stage procedures and be just as effective as PCNL. Our purpose was to review the literature for renal stones >2 cm managed by ureteroscopy and holmium lasertripsy. MATERIALS AND METHODS: A systematic review and quantitative meta-analysis was performed using studies identified by a literature search from 1990s (the first reported large renal stones treated ureteroscopically) to August 2011. All English language articles reporting on a minimum of 10 patients treated with FURSL for renal stones >2 cm were included. Two reviewers independently extracted the data from each study. The data of studies with comparable results were included into a meta-analysis. RESULTS: In nine studies, 445 patients (460 renal units) were reportedly treated with FURSL. The mean operative time was 82.5 minutes (28-215 min). The mean stone-free rate was 93.7% (77%-96.7%), with an average of 1.6 procedures per patient. The mean stone size was 2.5 cm. An overall complication rate was 10.1%. Major complications developed in 21 (5.3%) patients and minor complications developed in 19 (4.8%) patients. A subgroup analysis shows that FURSL has a 95.7% stone-free rate with stones 2-3 cm and 84.6% in those >3 cm (P=0.01), with a minor complication rate of 14.3% and 15.4%, respectively, and a major complication rate of 0% and 11.5%, respectively. CONCLUSION: In experienced hands, FURSL can successfully treat patients with stones >2 cm with a high stone-free rate and a low complication rate. Although the studies are from high-volume experienced centers and may not be sufficient to alter everyday routine practice, this review has shown that the efficacy of FURSL allows an alternative to PCNL.

Decreasing the cost of flexible ureterorenoscopic procedures.

OBJECTIVE: To treat calculus disease, perform diagnostic procedures, for endoscopic management of upper tract tumours and in selected cases for laser guided endopyelotomy there is an increase in the use of Flexible Ureterorenoscopy (FURS). METHODS: We wanted to prospectively audit the cost of flexible ureterorenoscopic procedures undertaken in our department between March 2009 and March 2010. RESULTS: Based on our business model, the cost of diagnostic FURS is £131 (equivalent to €157 or $196.50), FURS and lasertripsy for stones is between £296 and £429 (€355-€515 or $444-$644), and that for endoscopic management of upper tract transitional cell carcinomas is between £148 and £225 (€178-€270 or $222-$338). CONCLUSION: Our model shows a cost-efficient way of performing FURS procedures. As the cost of FURS comes down, more trainees will build hands-on experience in these procedures.