Investigating the associations of mucosal P2Y6 receptor expression and urinary ATP and ADP concentrations, with symptoms of overactive bladder.

AIM: To characterize purinergic signaling in overactive bladder (OAB). METHODS: Mucosal biopsies were taken by flexible cystoscopy from patients with storage symptoms referred to Urology Departments of collaborating hospitals. Immunohistochemistry (n = 12) and Western blot analysis (n = 28) were used to establish the qualitative and quantitative expression profile of P2Y6 in human mucosa. Participants from the general population provided a mid-stream urine sample. Bioluminescent assays were used to quantify adenosine triphosphate (ATP; n = 66) and adenosine diphosphate (ADP; n = 60) concentrations, which were normalized to creatinine (Cr) concentration. All participants completed a questionnaire (International Consultation on Incontinence Questionnaire - Overactive Bladder) to score urinary symptoms of OAB. RESULTS: P2Y6 immunoreactivity, more prominent in the urothelium (colocalized with the uroepithelial marker pan-cytokeratin), was more greatly expressed in OAB compared to age- and sex-matched controls (benign prostatic hyperplasia) without OAB symptoms. Mucosal P2Y6 was positively correlated only with incontinence (P = .009). Both urinary ATP and its hydrolysis product, ADP, an agonist to P2Y6, were positively correlated with total OAB symptom score (P = .010 and P = .042, respectively). CONCLUSIONS: The positive correlation of P2Y6 only with incontinence may indicate a different phenotype in OAB wet and warrants further investigation. Positive correlations of ATP and ADP with total OAB symptom score demonstrate upregulation in purinergic signaling in OAB; shown previously only in animal models. Further research is required to validate whether purinoceptors are indeed new therapeutic targets for this highly prevalent symptom complex.

Cystectomy outcomes in patients who have failed Radiofrequency-induced Thermo-chemotherapeutic Effect Mitomycin-C (RITE-MMC) treatment for high-risk non-muscle invasive bladder cancer (HRNMIBC)-Does it complicate surgery and adversely impact oncological outcome?

INTRODUCTION: The standard intravesical treatment for high risk non muscle invasive bladder cancer (HRNMIBC) is Bacillus Calmette-Guérin (BCG), with failure often resulting in cystectomy. Radiofrequency-Induced Thermo-chemotherapeutic Effect Mitomycin (RITE-MMC) can be an alternative in BCG failure. There has been concern that RITE-MMC may delay an inevitable cystectomy, make it more technically challenging and worsen prognosis. The aim of this study was to assess operative challenges and oncological outcome in patients undergoing cystectomy for HRNMIBC who received RITE-MMC, and contrast them with those that did not. PATIENTS AND METHODS: A retrospective study of a prospective cystectomy database was conducted. Patients treated from April 2011 to June 2017 were looked at. Inclusion criteria were HRNMIBC with BCG failure undergoing cystectomy. Patient demographics and tumour characteristics were analysed. Intraoperative blood loss and length of stay were used as surrogate markers for intra-operative difficulty. Kaplan-Meier curves were constructed to analyse all-cause mortality, cancer specific mortality and time to recurrence between the RITE-MMC treatment group and those that did not receive RITE-MMC. A multivariate analysis was conducted to assess factors that may influence readmission. RESULTS: Thirty-six patients who received RITE-MMC underwent cystectomy, compared to 102 that did not. Median ages were comparable at 72 and 69 years, respectively. Patients were followed up for a median of 24 months across the 2 groups. The commonest histological stage in both groups was CIS. There were no significant differences in intraoperative blood loss, length of stay and 90-day readmission between the 2 groups. There were proportionally fewer recurrences in the RITE-MMC group (16% vs. 19%) and median time to recurrence was longer in the RITE-MMC group (37 months vs. 24 months). Multivariate analysis did not reveal a significant correlation between pre-op RITE-MMC and post-operative readmission (P = 0.606). Survival curves show no significant difference in time to recurrence across both groups (P = 0.513), and no overall (P = 0.069) or cancer specific mortality (P = 0.129) dis-advantage was noted in the RITE-MMC group. CONCLUSION: We have found that RITE-MMC treatment does not result in a technically more challenging cystectomy and does not compromise oncological outcome compared to those patients undergoing cystectomy immediately post-BCG failure. We feel RITE-MMC remains a useful tool in a carefully selected group of patients who may not be willing to accept the morbidity of a cystectomy at the time, without significantly compromising their long-term outcome.

Evaluation of the accuracy of 3-dimensional ultrasonography of the kidney using an in vitro renal model.

OBJECTIVE: Three-dimensional ultrasonography (3DUS) has recently become a reality because of advances in ultrasound probes and machine processing ability. We have developed an anthropomorphic phantom of the human loin to assess both the accuracy of 3DUS of the kidney and its potential usefulness for training in ultrasonographically guided percutaneous renal intervention. METHODS: The model was built with easily available and inexpensive materials such as agar and latex with known ultrasonographic properties. The accuracy of 2-dimensional ultrasonography (2DUS) and 3DUS was assessed by measuring the dimensions of the pelvicalyceal system (PCS) ultrasonographically (pelvis width and calyx diameters) and then comparing these with measurements obtained at the time of construction. Radiology interventional trainees then punctured the PCS with 2DUS and 4-dimensional ultrasonographic (real-time/time-resolved 3DUS) guidance and reported the phantom's performance. RESULTS: The 3-dimensional nature of the model's PCS could be clearly visualized on 2DUS and 3DUS, and the scan characteristics were very similar to those in real life. Measurements using 3DUS proved to be closer to the true dimensions of the model's PCS than those using 2DUS. The mean error percentage for 2DUS measurements was -10.2%, and that for 3DUS was -2.2% (P < 0.0001). Interventional trainees were satisfied with the "tissue feel" and level of difficulty posed on puncturing the phantom. CONCLUSIONS: Three-dimensional ultrasonography proved to be more accurate than 2DUS for intrarenal measurements using this in vitro renal model. Three-dimensional ultrasonography has the potential to ease diagnostic renal scanning with the ability to further scrutinize and postprocess the scanned volumes. The model was realistic in its anthropomorphic properties and simulated human tissue during puncture.

What radiation exposure can a patient expect during a single stone episode?

PURPOSE: There is increasing concern about the risks of radiation exposure with the advent of new, more complex imaging modalities. For example, computed tomography (CT), with its obvious advantages, is being more commonly used in the investigation of acute flank pain. The likely radiation exposure a patient can expect during a single complete urinary stone episode was studied. PATIENTS AND METHODS: The hospital records of 60 consecutive unselected patients who had become or were rendered stone-free were studied. The effective radiation doses in milliSieverts (mSV) associated with diagnostic imaging modalities such as intravenous urogram studies and CT scans were calculated for St. George's Hospital. By combining these with the published effective doses for interventional examinations, the total effective dose over an entire stone episode was derived. RESULTS: There were a total of 60 patients with 68 stones (15 renal, 9 in the upper, 12 in the middle, and 32 in the lower ureter), with a median stone burden of 4 mm. Thirty-two patients had procedures performed, including extracorporeal shockwave lithotripsy SWL. Total effective doses ranged from 1.18 to 37.66 mSv (median 5.3 mSv; 95% CI of the median 4.13, 7.61). Renal and proximal ureteral stones resulted in the highest radiation exposures. CONCLUSION: In this study the median radiation dose per stone episode was calculated at 5.3 mSv, with higher doses in those with renal stones and those who required CT scans and other interventions. Monitoring and reduction of radiation exposure is advised for all patients presenting with urolithiasis.

The role of the multidisciplinary team in the management of deep infiltrating endometriosis.

The multidisciplinary team (MDT) is considered good practice in the management of chronic conditions and is now a well-established part of clinical care in the NHS. There has been a recent drive to have MDTs in the management of women with severe endometriosis requiring complex surgery as a result of recommendations from the European Society for Human Reproduction and Embryology (ESHRE) and British Society for Gynaecological Endoscopy (BSGE). The multidisciplinary approach to the management of patients with endometriosis leads to better results in patient outcomes; however, there are potentially a number of barriers to its implementation and maintenance. This paper aims to review the potential benefits, disadvantages and barriers of the multidisciplinary team in the management of severe endometriosis.

Prostate cancer: beware of disseminated intravascular coagulation.

Disseminated intravascular coagulation (DIC) is a pathological systemic condition resulting from aberrant activation of the coagulation system. It is characterised by the release and activation of procoagulants into the blood, with an associated consumption coagulopathy. Its association with solid and haematological malignancies is well described in literature. This case describes an elderly man, known to have prostate cancer, who following transurethral resection of the prostate developed DIC with haematuria, spontaneous ecchymoses and mucosal bleeding. Subsequent investigations revealed a prostate-specific antigen (PSA) >1000 µg/L, and staging CT showed multiple sclerotic metastatic lesions affecting the thoracic and lumbar vertebra, as well as infiltration into his left femur. Coagulation normalised with blood products and vitamin K within 1 week, and the patient responded to antiandrogen therapy with a reduction in pain and PSA on discharge.

Intravesical tension-free vaginal tape removal: is there a single solution?

Stress urinary incontinence (SUI) affects 10-20% of women in the general population. Surgery for stress incontinence has been performed on women for over a century, but with the advent of new urogynaecological sling procedures for its management, urological surgeons are having to deal with an increasing number of patients presenting with associated complications. With no clarity on the full range of possible complications or certain consensus on their optimal management, the ideal treatment remains a decision for the individual surgeon. In view of this, we felt it of common interest to review the literature for the history of sling procedures, present commonly arising complications, and seek to answer the question in the title.

Resin polymer and corrosion casting of the porcine pelvi-calyceal system: a useful model for investigating new imaging and endoscopic techniques of the upper urinary tract.

We describe the use of polyester resin casting of the pelvi-calyceal (PC) system as a method of evaluating the accuracy of new three-dimensional imaging technology such as ultrasound and computerised tomography. Thirty-eight kidneys from large white pigs were used for the study. We describe the process of preparation of the kidney and polyester resin for injection into the PC systems. The setting process of the resin is an exothermic reaction with an associated change in consistency. The PC systems of the kidneys were injected with resin in a controlled manner and casts obtained by maceration of the kidneys. Some of these kidneys had been distended previously with 11% glycerol and three-dimensional ultrasound reconstructions of their PC systems were compared to resin casts to assess accuracy of the reconstructions. Thirty-eight casts were created out of which 13 were poor. The quality of the casts improved with practice and pelvi-calyceal morphology could be faithfully recreated. Controlled perfusion and watching for signs such as a "turgid feel" of the kidney help avoid pelvi-calyceal disruption. Anatomically accurate casts of the kidney PC system can be created using polyester resin with the technique described. These casts can be a useful research and training tool with urological and radiological applications.

Percutaneous renal intervention: comparison of 2-D and time-resolved 3-D (4-D) ultrasound for minimal calyceal dilation using an ultrasound phantom and fluoroscopic control.

The rapid advances made by ultrasound in recent years have increasingly taken 3-D ultrasound (3DUS) and 4-D ultrasound (4DUS) from the research setting to the patient's bedside. There are still unexplored areas like renal percutaneous intervention, where 4DUS has yet to be proven an effective tool. Ultrasound-only guidance in renal percutaneous access is used in selected well-dilated pelvi-calyceal systems (PCS), and fluoroscopy is often utilized as an adjunct. Our aim was to compare 2-D and 4-D guidance for punctures, with fluoroscopy as control, using an in vitro ultrasound phantom. Agar and latex were the tissue-mimicking materials used for the construction of the phantom. The latex targets were designed to simulate multidirection-facing minimally dilated renal calyces. Two interventional fellows punctured the "calyces" using first 2DUS and then 4DUS guidance, making use of a different set of targets each time. The time to puncture, time to introduction of wire, quality of puncture (judged on fluoroscopy) and global rating of both modalities were documented. There was no significant difference between the times to puncture using 2DUS (1.8 min) and 4DUS (2 min). Nor was there a significant difference in the quality of puncture. 4DUS had a higher median difficulty rating. The multiplanar reformatted (MPR) longitudinal and transverse images were found to be the most useful for needle guidance. Cross hairs in all MPR images were not just useful in aligning the images on target but also as surrogate targets. The phantom was found to be robust, with only one instance of air introduction after 30 punctures. We have found that 4DUS is at least as good as 2DUS in terms of quality of punctures in vitro. The technology still has some way to go as frame rates, transducer size and resolution improve.