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Editorial: Robotic and conventional open radical cystectomy lead to similar postoperative health-related quality of life

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In this month’s issue of BJU International, Messer et al. [1] devise a prospective randomised trial to compare postoperative health-related quality of life (HRQoL) after robot-assisted (RARC) vs conventional open radical cystectomy (ORC). The investigators evaluated 40 patients over a follow-up period of 1 year and found no significant difference in HRQoL between surgical approaches. Moreover, they showed that the postoperative decrease in HRQoL returns to baseline within 3 months of surgery.

RC is one of the most challenging and potentially mutilating surgical interventions in the urological field and represents the standard-of-care treatment for patients with muscle-invasive bladder cancer. It is associated with a non-negligible risk of morbidity and mortality [2]. With the advent of new technologies, such as the Da Vinci surgical robot, carefully designed studies are needed to weigh the potential benefits of a novel approach against the increased costs associated with such tools. While RARC holds the promise of combining the benefits of a minimally invasive intervention with the precise robotic translation of the surgeon’s movements, these claims remain to be definitely proven in the clinical setting. As such, further elucidating the effect of surgical approach on perioperative outcomes after RC is essential for treatment planning, patient counselling and informed decision-making before surgery.

QoL is increasingly used as a quantitative measure of treatment success [3, 4]. These measures are gaining considerable traction in the USA, as reimbursements will soon be tied to patient satisfaction. While previous retrospective studies suggest that RARC has comparable perioperative oncological outcomes with potentially lower morbidity relative to ORC [5], there is a scarcity of high-quality evidence on HRQoL outcomes of RARC vs ORC. The difficulties of conducting randomised trials in the surgical setting are reflected by the relatively few participants in the Messer et al. [1] trial. Nonetheless, in their pilot study, the authors demonstrated the feasibility of a HRQoL trial in RC patients. Furthermore, they deliver initial evidence on the impact of surgical approach on HRQoL after RC.

From a clinical perspective, the authors contribute interesting findings to the ongoing debate. Their results suggest that the potential benefits of robot-assisted surgery on HRQoL may be limited in patients undergoing complex oncological surgery such as RC. Several hypotheses may be pertinent to their conclusions. For example, performing an open urinary diversion after RARC that can take as much time as the actual extirpative RC may mitigate any potential benefit of the minimally invasive approach. Furthermore, the study findings may be largely influenced by the surgical skills of the participating surgeons. Maybe the correct interpretation of their study findings is that there was no significant difference in HRQoL outcomes between ORC and RARC, at the institution where the trial was performed.

Nonetheless, the authors suitably demonstrate the feasibility of performing a randomised trial in this field and pave the way towards adequately powered, randomised multicentre trials that can provide further evidence on what impact RARC may have on perioperative outcomes and beyond.

Read the full article

Julian Hanske, Florian Roghmann, Joachim Noldus and Quoc-Dien Trinh*

Department of Urology, Marien Hospital, Ruhr-University Bochum, Herne, Germany, and *Division of Urologic Surgery and Center for Surgery and Public Health, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

References

1 Messer JC, Punnen S, Fitzgerald J, Svatek R, Parekh DJ. Health-related quality of life from a prospective randomised clinical trial of robot-assisted laparoscopic vs open radical cystectomy. BJU Int 2014; 114: 896–902

2 Roghmann F, Trinh QD, Braun K et al. Standardized assessment of complications in a contemporary series of European patients undergoing radical cystectomy. Int J Urol 2014; 21: 143–9

3 Cookson MS, Dutta SC, Chang SS, Clark T, Smith JA Jr, Wells N. Health related quality of life in patients treated with radical cystectomy and urinary diversion for urothelial carcinoma of the bladder: development and validation of a new disease specific questionnaire. J Urol 2003; 170: 1926–30

4 Loppenberg B, von Bodman C, Brock M, Roghmann F, Noldus J, Palisaar RJ. Effect of perioperative complications and functional outcomes on health-related quality of life after radical prostatectomy. Qual Life Res 2014. doi: 10.1007/s11136-014-0729-1

5 Kader AK, Richards KA, Krane LS, Pettus JA, Smith JJ, Hemal AK. Robot-assisted laparoscopic vs open radical cystectomy: comparison of complications and periopera

 

BCG – An all or nothing treatment for NMIBC?

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November 2014 ushered in the third year of the international urology journal club (@iurojc) and also marked the 2500th follower of @iurojc.

This month’s article was published in European Urology (@Uroweb) on October 10, 2014, Sequential Combination of Mitomycin C Plus Bacillus Calmette-Guerin (BCG) Is More Effective but More Toxic Than BCG Alone in Patients with Non-Muscle-Invasive Bladder Cancer in Intermediate- and High-risk Patients: Final Outcome of CUETO 93009, a Randomized Prospective Trial.

 

The discussion was once again well attended by many of the Urology twitter gurus and leaders in the field of intravesical chemotherapy for non-muscle-invasive bladder cancer (NMIBC) (@davisbj, @JimCatto, @DrHWoo, @jimmontie, @uretericbud, @shomik_s, @UroDocAsh, etc).

Given the recent worldwide shortage of BCG, this article proved timely for discussion @iurojc. The authors from Spain conducted a prospective, randomized trial including 407 patients with intermediate- to high-risk NMIBC – 211 patients were allocated to receive mitomycin-C (MMC) and BCG, and 196 patients to receive BCG-alone. At 5 years, the disease free interval significantly improved with sequential MMC and BCG compared to BCG alone (HR 0.57, 95%CI 0.39-0.83, p=0.003), and reduced the relapse rate from 33.9% to 20.6%. However, sequential treatment lead to increased toxicity even after lowering the MMC dose to 10mg (p<0.001). The authors concluded that due to higher toxicity, sequential MMC and BCG therapy should only be given to patients with high likelihood of tumor recurrence (ie. recurrent T1 tumors).

The discussion started with the point being made that BCG strain may influence outcomes, with reference made to the @Uroweb article discussing the outcomes of NMIBC and BCG strain.

Subsequently, we were reminded that patients with recurrent T1 tumors are at high risk for disease progression and mortality, and that appropriately fit patients should be offered aggressive treatment (radical cystectomy).

@uretericbud also made the point that we aggressively treat T1 prostate and T1 kidney cancer, which have low cancer specific mortality, however cystectomy is the last resort for T1 bladder cancer (mortality >30%).

The reality of the worldwide BCG shortage was also highlighted during the discussion, ultimately affecting other ongoing MMC and BCG trials.

This month’s discussion concluded with a conversation regarding treatment options during the BCG shortage.  The conclusion among the discussants was for MMC during the induction phase of treatment.

Overall, the consensus was that although the results of MMC and BCG in sequence are encouraging, appropriately fit patients may still benefit from radical cystectomy for recurrent T1 disease. With the worldwide shortage of BCG, perhaps this decision will be easier to make. Happy #movember everyone.

The winner of the Best Tweet prize is Vincent Misrai who will receive a complimentary registration to the USANZ Annual Scientific Meeting to be held in Adelaide, Australia in March 2015.

Thank you to the Urological Society of Australia and New Zealand (USANZ) for providing this generous prize.  Thanks also to European Urology for enabling this paper to be open access for the November #urojc.

Zach Klaassen is a Resident in the Department of Surgery, Section of Urology Georgia Regents University – Medical College of Georgia Augusta, USA. @zklaassen_md
 

Editorial: Statins and biochemical recurrence after radical prostatectomy – who benefits?

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In the present issue of the BJUI Allott et al. [1] report results from a study where they used the Shared Equal Access Regional Cancer Hospital (SEARCH) database to explore the risk of biochemical recurrence (BCR) after radical prostatectomy (RP) among men who used statins after RP. They report improved BCR-free survival among statin users, especially among men with high-risk disease at baseline. The results provide some new insights into the current discussion on statins and prostate cancer outcomes.

Statins have recently shown promise as chemotherapeutic agents against prostate cancer. There is conflicting evidence on the effect on overall prostate cancer risk, but most studies able to evaluate the risk by tumour stage have reported lowered risk of advanced prostate cancer among statin users compared with the non-users [2], and lowered prostate cancer-specific mortality [3].

Taken together, these epidemiological findings suggest that statins may not strongly lower the risk of initiation of prostate cancer, but may be able to slow down the progression of the most dangerous form of the disease. In vitro studies support this by reporting growth inhibition and lower metastatic activity of prostate cancer cells after statin treatment [4].

Despite this, there has been recent controversy on statins’ effect on BCR of prostate cancer after radical treatment. A recent meta-analysis concluded that statin users may have a lower risk of BCR after external beam radiation therapy, but not after RP [5]. This could be due to statins acting as radiation sensitizers. Reports of improved BCR-free survival in statin users after brachytherapy would support this [6].

However, there are also differences in the characteristics of patients managed with RP or radiation therapy. Men undergoing RP have localised disease, which usually means low- to medium-grade tumours (Gleason ≤7), as high-grade disease (Gleason 8–10) progresses early and is more often locally advanced or already metastatic at diagnosis, leading to the choice of radiation therapy with neoadjuvant androgen deprivation instead of RP if curative treatment is still deemed possible.

This leads to the question whether the differing association between statins and BCR by treatment method is explained by patient selection, and whether statins are most effective against progression of high-grade disease. The study reported by Allott et al. [1] in this issue of the BJUI certainly suggests so. They report lowered risk of BCR among men who used statins after RP. They were able to study the effect of statin usage occurring after RP, not just usage at the time of RP. When the analysis was stratified by tumour characteristics, the improvement in relapse-free survival was strongest among men with high-risk disease (Gleason score ≥4 + 3; positive surgical margins).

The present study [1] supports the notion that statins could target a mechanism that is essential for progression of high-risk prostate cancer. This would be in concordance with the previously reported lowered risk of advanced prostate cancer and decreased prostate cancer mortality among statin users, as high-grade/high-risk cancer is the type progressing into advanced and fatal stages. On the other hand, if statins do not affect low-grade prostate cancer, this could explain why many RP series have not observed differences in biochemical relapses by statin use, as patients in these studies often have low-grade disease.

As always, statins’ benefits against prostate cancer are not really proven until verified in randomised clinical trials properly designed and powered to detect a difference in cancer endpoints. Designers of such trials should consider targeting the statin intervention to men with high-grade and/or high-risk prostate cancer for efficient study design.

Read the full article

Teemu J. Murtola*†

*School of Medicine, University of Tampere, and † Department of Urology, Tampere University Hospital, Tampere, Finland

References

1 Allott EH, Howard LE, Cooperberg MR et al. Postoperative statin use and risk of biochemical recurrence following radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. BJU Int 2014; 114: 661–6

2 Bansal D, Undela K, D’Cruz S, Schifano F. Statin use and risk of prostate cancer: a meta-analysis of observational studies. PLoS ONE 2012; 7:e46691

3 Yu O, Eberg M, Benayoun S et al. Use of statins and the risk of death in patients with prostate cancer. J Clin Oncol 2014; 32: 5–11

4 Brown M, Hart C, Tawadros T et al. The differential effects of statins on the metastatic behaviour of prostate cancer. Br J Cancer 2012; 106: 1689–96

5 Park HS, Schoenfeld JD, Mailhot RB et al. Statins and prostate cancer recurrence following radical prostatectomy or radiotherapy: a systematic review and meta-analysis. Ann Oncol 2013; 24: 1427–34

6 Moyad MA, Merrick GS, Butler WM et al. Statins, especially atorvastatin, may improve survival following brachytherapy for clinically localized prostate cancer. Urol Nurs 2006; 26: 298–303

 

Editorial: Evolution of extracorporeal shockwave lithotripsy (ESWL)

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Much has changed since the introduction of extracorporeal shockwave lithotripsy (ESWL); however, in many ways the principles remain constant. This manuscript by Jagtap et al. [1] is a large series of patients over 25 years and encapsulates the changes in ESWL over that time. This paper has all the limitations inherent in a retrospective review but within this offers interesting data. In particular the use of two different machines and refinements in technique are eloquently described. This shows an improvement due to both the change in technology but also in the importance of modifications of technique. The particular factors improving stone-free rate (SFR) were; better localisation with ultrasonography and X-ray, better coupling and use of coupling gel, change in selection criteria for both the patient and stone, ramping up the power and a staff training programme. This emphasis on technique is especially pertinent in healthcare systems where mobile lithotripters are still in use. These are renowned to have lower SFRs than static machines, which may be due to the technical delivery of treatment as much as the efficacy of the lithotripter.

What is the future for ESWL? The paper reflects the perception globally that whilst the incidence of urolithiasis is increasing, the use of ESWL is not increasing at the same rate, particularly for ureteric stones, and they cite the potential factors for this. This has also been noted in the UK and our own recent review of Hospital Episode Statistics (HES) data even suggest the rate of ESWL has plateaued for both ureteric (3000/year) and renal (19 500/year) stones in the last 3 years [2, 3]. There has been discussion within the UK about centralising endourology services using the same model as for cancer, with provision of static lithotripters within those centres. This would potentially have the advantage of creating high-volume centres with quality being easier to standardise and monitor; however, this would have to be balanced against patients probably having to travel further to access ESWL. The use of Hounsfield units remains a topic of debate with conflicting data and limited clinical application [4, 5]. Optimising targeting to minimise tissue damage with maximal stone fragmentation remains a challenge and modifications to lithotripters with dual-imaging modalities, dual heads, alterations in shockwave delivery rate, control of respiratory effort and novel feedback devices have had limited success. Increasing levels of obesity within developed countries are a factor in the utilisation of ESWL, as there is a limit on focal distance. All of these factors along with the continued improvement in the optics, miniaturisation of ureteroscopes and advent of holmium laser have contributed to a surge in the use of ureteroscopy, despite publications and guidelines showing similar success rates [6].

Read the full article

Kay Thomas

Clinical lead for Urology, Honorary Senior Lecturer Kings College London, UK

References

1 Jagtap J, Mishra S, Bhattu A, Ganpule A, Sabnis R, Desai M. Evolution of shockwave lithotripsy (SWL) technique: a 25-year single centre experience of >5000 patients. BJU Int 2014; 114: 748–53

2 Turney BW, Reynard JM, Noble JG, Keoghane SR. Trends in urological disease. BJU Int 2011; 109: 1082–7

3 Withington J. Personal communication from Royal College of Surgeons. July 2014

4 Pareek G, Armenakas A, Fracchia JA. Hounsfield units on computerized tomography predict stone free rates after extracorporeal shock wave lithotripsy. J Urol 2012; 169: 1679–81

5 Foda K, Abdeldaeim H, Youssif M, Assem A. Calculating the number of shock waves, expulsion time and optimum stone parameters based on noncontrast computerized tomography characteristics. Urology 2013; 82: 1026–31

6 Türk C, Knoll T, Petrik A et al. EAU Guidelines on Urolithiasis, 2014. Available at: https://www.uroweb.org/gls/pdf/22%20Urolithiasis_LR.pdf. Accessed July 2014

 

Editorial: ‘Discontent is the first necessity of progress’, Thomas A. Edison

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This study from Kaag et al. [1] investigates predictors of renal functional decline after radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC). They evaluate early (2 months) and late (6 months) predictors of renal functional decline, finding that on a multivariable model only age at surgery and preoperative renal function were independently associated with early postoperative function. This is an intuitive finding whereby we expect older patients and those with lower renal function to have a more dramatic decrease in renal function after RNU.

Age, preoperative renal function, and Charlson score were associated with late functional recovery. The latter is a counterintuitive finding, as higher Charlson score was associated with less decrease in renal function. Charlson comorbidity was not significant on univariate analyses. Why it would become significant on multivariate is unclear. Whether it is an artifact related to study methodology or is a real phenomenon will require further study.

Unquestionably, this study [1] adds to the growing discontent of our current management of UTUC. The authors cogently discuss the issues related to better risk stratification as a natural consequence of instituting a neoadjuvant chemotherapy paradigm in those with high-risk disease. Multiple retrospective studies have failed to show a benefit of adjuvant chemotherapy, whereas now we have a matched-cohort study showing significant rates of downstaging and complete remission [2], and as well significantly improved 5-year survival, with institution of a neoadjuvant paradigm [3]. One cannot view the dismal outcomes of this disease without being discontent and wishing for progress. We need to continue getting out the message to not only urologists who reflexively institute RNU in patients with a risk-unstratified upper tract filling defect, but as well many medical oncologists who can only function based on guidance from level I data, which for this disease, will be a long time coming.

Read the full article

Surena F. Matin

Department of Urology, MD Anderson Cancer Center, Houston, TX, USA

References

1 Kaag M, Trost L, Thompson RH et al. Pre-operative predictors of renal function decline following radical nephroureterectomy for upper tract urothelial carcinoma. BJU Int 2014; 114: 674–9

2 Matin SF, Margulis V, Kamat A et al. Incidence of downstaging and complete remission after neoadjuvant chemotherapy for high-risk upper tract transitional cell carcinoma. Cancer 2010; 116: 3127–34

3 Porten S, Siefker-Radtke AO, Xiao L et al. Neoadjuvant chemotherapy improves survival of patients with upper tract urothelial carcinoma. Cancer 2014; 120: 1794–9

Lessons learned from Asian Urology

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Glasgow has been in the news a lot this year. The fantastic Commonwealth Games were followed by an excellent Société Internationale d’Urologie (SIU) meeting with its unique Scottish flavour. This month we move our attention to two other nations that have hosted the SIU – China and India. We present two large studies, which are well worth your reading pleasure, not just because of their sheer size but also for their messages and citability.

Since the initial discovery in 2007 of ketamine-associated cystitis by Shahani et al. [1] in Canada, scattered cases had also been reported in some European countries including the UK. However, the gravity of this ketamine problem was subsequently found to be far greater in Asian countries, particularly Hong Kong, Taiwan, Mainland China and Malaysia.

Although ketamine-associated uropathy is a medical problem, it takes root in much deeper social problems, and in turn perpetuates these problems and produces new issues. As the devastating effect of ketamine abuse on the society is unveiled, there are numerous collaborations between Hong Kong and Mainland China to combat it. Government and non-government organisations join hands in educating the public, youths in particular, on the irreversible damage that ketamine can cause to body and mind. More stringent laws have been enacted against drug traffickers, with high-profile enforcements. Abundant funds have also been set up to encourage research in this field.

With all these concerted efforts, according to official statistics in Hong Kong and Mainland China, the number of ketamine abusers is on the decline. However, this is no reason for complacency, as the numbers of abusers we capture probably represent only the ‘tip of the iceberg’. More and more evidence is indicating a substantial population of undiscovered ketamine abusers, who sniff ketamine stealthily at home for years without being noticed by their families.

Any effective solution to ketamine-associated uropathy [2] must involve identifying and extending help to this vast hidden group of abusers. The problem is daunting by its sheer magnitude. There are in addition, delicate issues of privacy, rights and self-esteem that require great sensitivity and patience. It is a job that requires experts from different specialties to cooperate. Urologists must work with social workers, teachers, paediatricians, psychiatrists, psychologists, nurses, occupational therapists and others. Last but not least, parental and family support is paramount in helping our youth to win this fight.

For those endourologists busily treating stone disease we highlight the evolution of shockwave lithotripsy (SWL) over 25 years in >5000 patients [3]. In many parts of the world, not just Asia, extracorporeal SWL (ESWL) has seen a drop in its popularity in parallel with an increase in the use of percutaneous nephrolithotomy (PCNL) and ureteroscopy. Patients seem to be more inclined to be stone-free with fewer interventions even if these are of an invasive nature.

For those readers more interested in immediacy through our web journal, the Best of China virtual supplement is the one not to miss. There have been many calls for a BJUI Android app from our friends in the East. We are almost there!

Read the full article

Peggy Sau-Kwan Chu and Prokar Dasgupta*

Division of Urology, Department of Surgery, Tuen Mun Hospital, Hong Kong *King’s College London, Guy’s Hospital, London, UK

References

1 Shahani R, Streutker C, Dickson B, Stewart RJ. Ketamine-associated ulcerative cystitis: a new clinical entity. Urology 2007; 69: 810–2

2 Tam YH, Ng CF, Pang KK et al. One-stop clinic for ketamine-associated uropathy: report on service delivery model, patients’ characteristics and non-invasive investigations at baseline by a cross-sectional study in a prospective cohort of 318 teenagers and young adults. BJU Int 2014; 114: 754–60

3 Jagtap J, Mishra S, Bhattu A, Ganpule A, Sabnis R, Desai M. Evolution of shockwave lithotripsy (SWL) technique: a 25-year single centre experience of >5000 patients. BJU Int 2014; 114: 748–53

 

Step-by-Step. Real time TRUS-guided free-hands technique for focal cryoablation of the prostate

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Real-time transrectal ultrasonography-guided hands-free technique for focal cryoablation of the prostate

Andre Luis de Castro Abreu, Duke Bahn*, Sameer Chopra, Scott Leslie, Toru Matsugasumi, Inderbir S. Gill and Osamu Ukimura

USC Institute of Urology, Catherine and Joseph Aresty Department of Urology, Center for Prostate Cancer Focal Therapy, Keck School of Medicine, University of Southern California, Los Angeles, and *Prostate Institute of America, Community Memorial Hospital, Ventura, CA, USA

How to Cite: de Castro Abreu, A. L., Bahn, D., Chopra, S., Leslie, S., Matsugasumi, T., Gill, I. S. and Ukimura, O. (2014), Real-time transrectal ultrasonography-guided hands-free technique for focal cryoablation of the prostate. BJU International, 114: 784–789. doi: 10.1111/bju.12795

Read the full article

Objectives

To describe, step-by-step, our hands-free technique for focal cryoablation of prostate cancer.

Materials and Methods

After detailed discussion of its limitations and benefits, consent was obtained to perform focal cryoablation in patients with biopsy-proven unilateral low- to intermediate-risk prostate cancer. The procedure was performed transperineally, using a hands-free technique (without an external grid template) under real-time bi-plane transrectal ultrasonography (TRUS) guidance, using an argon/helium-gas-based third generation cryoablation system. Follow-up consisted of validated questionnaires, physical examination, PSA measures, multiparametric TRUS and/or magnetic resonance imaging (MRI) and mandatory biopsy.

Results

The important steps for achieving safety, satisfactory oncological and functional outcomes included: patient selection, including TRUS/MRI fusion target biopsy; thermocouple and cryoprobe placement with a hands-free technique, allowing delivery in unrestricted angulations according to the prostatic contour, the course of the neurovascular bundle and the rectal wall angle; and hands-free bi-plane TRUS probe manipulation to facilitate real-time monitoring of anatomical landmarks at the ideal angle of the image plane. To achieve a lethal temperature in the known cancer area, while preserving the urinary sphincter, neurovascular bundle, urethra and rectal wall, continuous intraoperative control of the thermocouple temperatures was necessary, as were real-time TRUS monitoring of ice-ball size, control of the energy delivered and the use of a warming urethral catheter.

Conclusion

We have described step-by-step the focal cryoablation of prostate cancer using a hands-free technique. This technique facilitates the effective delivery of cryoprobes and the intra-operative real-time quick manipulation of the TRUS probe.

 

Editorial: Where next in ketamine uropathy? Dedicated management centres?

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Tam et al. [1] in this month’s BJUI publish the largest prospective cohort to date on ketamine uropathy (KU). KU is a growing international problem since initial reports in 2007 from Canada and Hong Kong, where ketamine is second only to heroin in popularity amongst drug takers [2, 3]. Prevalence of KU may be higher than previously thought with up to a quarter of people misusing ketamine reporting urinary symptoms [4].

Importantly, the Tam et al. [1] paper demonstrates the benefit of stopping ketamine amongst those presenting with KU. Dose, frequency and dependency upon ketamine have been reported as risk factors for developing KU [1, 4]. Achieving cessation is not always straightforward following identification, assessment and urology input. Consistent with the Winstock et al. [4] recommendations a multi-disciplinary approach is required to assess symptoms and risk profile. The recommendation of Tam et al. of a one-stop clinic is thus appealing.

The key to diagnosing KU, is a focused history including specific drug use, performing non-invasive uroflowmetry investigations and upper tract imaging. Urologists need to be aware of motivational interviewing strategies, and incorporate them in their assessment. Presenting symptoms include dysuria, frequency, urgency and pain that may be consequent on the small contracted bladder that develops in KU. The diagnosis should exclude other bladder diseases and cystoscopy and biopsy is advised [5]. If left late, pain and bladder contraction can be so severe that bladder augmentation, cystectomy and neobladder or ileal conduit may be required [6]. It is strongly advised that ketamine use is stopped before, as ketamine metabolites will be readily absorbed through bowel and potentially lead to a fatal overdose.

In the Tam et al. [1] paper, renal ultrasonography (US, performed on a second visit) showed hydronephrosis in 8%. However, their client uptake for renal US was only 50%. Having a one-stop KU clinic with integrated US is more patient-friendly and consistent with our unit’s one-stop clinic approach [7]. Management of hydronephrosis and reversal of renal impairment is crucial and more definitive surgical management may be warranted. Renal failure secondary to KU may rise as the numbers of ketamine users continues to climb.

What makes KU interesting and difficult to manage is the stigmatising nature of illicit drug use that makes patients uncomfortable in disclosing ketamine use. Patients may not recognise the causal link between ketamine use and their discomfort. Instead symptoms may be attributed to other pathologies such as UTIs, sexually transmitted infections (common in high-risk drug use behaviour), excessive alcohol or caffeine consumption or be mistaken for ‘K cramps’, which may be a direct result of ketamine itself [8]. Pain team input may be required. The Bristol unit report managing KU pain with buprenorphine patches, co-codamol (combination of codeine phosphate and paracetamol) and amitriptyline [5], whereas the Tam et al. [1] unit prefer a combination of diclofenac, anti-cholinergics and opioids.

Promoting early treatment seeking will help reduce the time between symptom onset and assessment. However, due to the nature of ketamine patients, their history may be unreliable, follow-up intermittent and compliance poor. These issues may lead to a delay in presentation and referral.

Ultimately, what is required is a raised awareness among users of the potential for ketamine to cause irreversible bladder and upper tract harm. While abstinence may be the most attractive option for clinicians this remains an unrealistic and unhelpful approach for many users including those most at risk. Consideration needs to be given to support users to reduce harm and to maintain abstinence once achieved. Stopping ketamine may require psychological, addiction and even psychiatric support.

Importantly, clinicians should accept that ketamine users are interested in their own health and wellbeing. They may appreciate learning strategies to minimise their harm risk. Harm reduction strategies as outlined in the Global Drug Survey Highway Code (stay well hydrated, have breaks between use periods, and avoid alcohol use) not only encourage safer use but can raise awareness of symptoms suggestive of KU [9].

Given the complexity of ketamine patients and the fact that users share information, provision of high-quality care from a dedicated understanding team has obvious advantages. An age-appropriate unit including a urologist, psychiatrist, pain management consultant and a sexual health expert provides a comprehensive approach. A one-stop clinic, as described by Tam et al., may expedite initial assessment but withdrawal from ketamine requires long-term investment to achieve overall improvements in KU outcomes.

The key message to get out to the ketamine-using community is that as a rule, marked improvement in function follows cessation of ketamine use. There is an increasing role for the urologist to be a source of credible information to ketamine users and healthcare professionals. Finally, dedicated management centres offering a holistic approach to the management of these patients seems ideal. This will concentrate exposure and understanding of KU, which we hope will help continue to improve management of this difficult condition.

Read the full article

Claire F. Taylor, Adam R. Winstock* and Jonathon Olsburgh

Young Onset Urology Clinic, Urology/Renal Unit, Guy’s and St Thomas’ Hospital, and *South London and Maudsley NHS Trust, London, UK

References

1 Tam YH, Ng CF, Pang KK et al. One-stop clinic for ketamine-associated uropathy: report on service delivery model, patients’ characteristics and non-invasive investigations at baseline by cross-sectional study in a prospective cohort of 318 teenagers and young adults. BJU Int 2014; 114: 754–60

 

2 Chu PS, Kwok SC, Lam KM et al. ‘Street ketamine’-associated bladder dysfunction: a report of ten cases. Hong Kong Med J 2007; 13: 311–3

 

3 Shahani R, Streutker C, Dickson B, Stewart RJ. Ketamine-associated ulcerative cystitis: a new clinical entity. Urology 2007; 69: 810–2

 

4 Winstock AR, Mitcheson L, Gillatt DA, Cottrell AM. The prevalence and natural history of urinary symptoms among recreational ketamine users. BJU Int 2012; 110: 1762–6

 

5 Wood D, Cottrell A, Baker SC et al. Recreational ketamine: from pleasure to pain. BJU Int 2011; 107: 1881–4

 

6 NgCF,ChiuPK,LiMLetal.Clinical outcomes of augmentation cystoplasty in patients suffering from ketamine-related bladder contractures. Int Urol Nephrol 2013; 45: 1245–51

 

7 Coull N, Rottenberg G, Rankin S et al. Assessing the feasibility of a one-stop approach to diagnosis for urological patients. AnnRCollSurg Engl 2009; 91: 305–9

 

8 Winstock AR, Mitcheson L. New recreational drugs in the primary care approach to patients who use them. BMJ 2012; 344: e288

 

9 Global Drug Survey Ltd. Global Drug Survey Highway Code. Available at: https://www.globaldrugsurvey.com/wp-content/uploads/2014/04/The -High-Way-Code_Ketamine.pdf. Accessed September 2014

 

Editorial: Extent of lymph node metastases

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The role of prostatectomy in lymph node metastasized prostate cancer has been subject to changing opinions. Classically, a nodal dissection was performed as the initial step in the procedure and prostatectomy was avoided in men with cryosection-proven metastases. Biochemical recurrence during the first 3 years occurs in the majority of men with pN1 disease [1]. Early data from randomized trials shows only a 50% prostate cancer-specific survival 12 years after prostatectomy and nodal metastases without immediate adjuvant treatment [2]. Recently, Passoni et al. [3] showed a higher 10-year overall survival of 82.8% in men with nodal metastases, of whom the majority were treated with adjuvant androgen ablation and/or radiotherapy. This percentage is remarkably similar to the treatment arm of the earlier-mentioned study reported by Messing et al. [2], which showed a 10-year disease-specific survival of >80%. At 10 years about half the patients who died, did so from prostate cancer; therefore, although reasonable intermediate range survival can be obtained in men with nodal metastases of prostate cancer, the major cause of death remains prostate cancer when surgery is applied at the age of 65 years. Although adjuvant androgen ablation may improve survival, as suggested by the above-mentioned observations, some men may not experience recurrence after resection of nodal metastases and would experience the toxicity of androgen ablation unnecessarily. The identification of these men would reduce costs and toxicity.

Passoni et al. [3] presented a multicentre study on prognostic factors after prostatectomy for node-positive disease. The number of removed nodes (median 10) seems relatively low compared with the 17 reported in their earlier single-centre study, but may be a good reflection of urological practice in general. By comparison, the percentage of men who underwent adjuvant radiotherapy in the multicentre study was low (16%). Data from da Pozzo et al. [4] suggest that adjuvant radiotherapy may be of benefit in men with limited nodal metastases. It would be of interest to study whether men with a later biochemical recurrence would be those that did experience recurrence only locally and therefore would be those most likely to benefit from adjuvant (or salvage) radiotherapy.

In the current study by Passoni et al. [1] in the BJUI, the follow-up was relatively short (16 months). Earlier data from this author group showed that number of positive nodes and lymph node density were good predictors of cancer-specific survival after prostatectomy. This earlier observation is now confirmed in a multicentre analysis with a different endpoint: biochemical recurrence. What is notable is the fact that this confirmation was obtained in a series of patients with fewer nodes removed. The value of the marker ≤2 positive nodes becomes limited with the observation that this group contained 85% of men in their series. The second marker found, the size of the node, showed a more general distribution but as a single marker had no predictive value. The differences in Harrel’s c values from the base model containing other clinical characteristics are limited and reproducibility of measures needs attention. Still, the observation that extent of nodal metastases is of prognostic value after surgery is notable.

Ideally, markers could predict the absence of further disease progression in men after prostatectomy for nodal metastasized prostate cancer. None of the studied characteristics fulfill this need because at 36 months after prostatectomy the majority of men, even those in the best prognostic group, do experience biochemical recurrence that will result in prostate cancer-related death. Gleason score is a strong predictor of the presence of nodal metastases [5], and some have suggested that nodal Gleason grade is of prognostic value in men with pN+ disease. Until these markers have been further evaluated, it remains important to address the fact that reported cancer-specific survival in most men with pN+ disease is >10 years [6]. Although tempting to speculate that prostatectomy and (extended) lymph node dissection plays a role in this, the almost inevitable development of biochemical recurrence reported in the current study by Passoni et al. [1], even in patients in the best prognostic group, stresses the systemic nature of this disease which will require a multimodality approach in most men at some point.

Read the full article

Henk G. van der Poel

Department of Urology, Netherlands Cancer Institute, Amsterdam, The Netherlands

References

1 Passoni N, Fajkovic H, Xylinas E. Prognosis of patients with pelvic lymph node metastasis following radical prostatectomy: value of extranodal extension and size of the largest lymph node metastasis. BJU Int 2014; 114: 503–10

2 Messing EM, Manola J, Yao J et al. Immediate versus deferred androgen deprivation treatment in patients with node-positive prostate cancer after radical prostatectomy and pelvic lymphadenectomy. Lancet Oncol 2006; 7: 472–9

3 Passoni NM, Abdollah F, Suardi N et al. Head-to-head comparison of lymph node density and number of positive lymph nodes in stratifying the outcome of patients with lymph node-positive prostate cancer submitted to radical prostatectomy and extended lymph node dissection. Urol Oncol 2013; 29: 29.e21–8

4 Da Pozzo LF, Cozzarini C, Briganti A et al. Long-term follow-up of patients with prostate cancer and nodal metastases treated by pelvic lymphadenectomy and radical prostatectomy: the positive impact of adjuvant radiotherapy. Eur Urol 2009; 55: 1003–11

5 Ross HM, Kryvenko ON, Cowan JE, Simko JP, Wheeler TM, Epstein JI. Do adenocarcinomas of the prostate with Gleason score (GS)</=6 have the potential to metastasize to lymph nodes? Am J Surg Pathol 2012; 36: 1346–52

6 Touijer KA, Mazzola CR, Sjoberg DD, Scardino PT, Eastham JA. Long-term outcomes of patients with lymph node metastasis treated with radical prostatectomy without adjuvant androgen-deprivation therapy. Eur Urol 2013; 65: 20–5

Rocktober – Keep on rocking #urojc

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We celebrated the two-year anniversary of the international urology journal club this month (@iurojc) with record participation. There were over 500 tweets in the 48 hour discussion of this month’s article, published in New England Journal of Medicine on September 18, 2014, Ultrasound versus Computed Tomography for Suspected Nephrolithiasis. It was a true multidisciplinary discussion with nephrologists, EM docs, and study author, radiologist Rebecca Smith-Bindman tweeting.

This was a multi-institutional prospective randomized control study evaluating bedside and radiology ultrasonography versus CT as the first test performed for patients presenting to the ED with flank or abdominal pain. Patients who initially underwent ultrasound could also receive a CT if the provider felt necessary based on clinical presentation and ultrasound findings. In terms of the primary endpoints, authors found no significant difference across the three groups in high-risk diagnoses with complications related to missed or delayed diagnoses. There was significantly less 6-month cumulative radiation exposure in patients assigned to the ultrasonography groups compared to those assigned to CT. Conclusions of this study in the form of a tweet: Get US first #noharmdone #lessradiation.

Conversation first focused on clarifying the main conclusions of this article. Notably, ED physicians were the focus of this study, who care whether the patient will be admitted or sent home. Information about size, location, etc of stones was omitted from the study since the goal was not definitive stone treatment.

Some of the limitations of the study were brought up early on. First of all, obese patients were excluded (men >129 kg and women >113 kg).

Additionally, the definition of being diagnosed with a stone only applied to individuals who reported passing a stone or having a stone surgically removed.

Much of the conversation focused on how this approach may be beneficial in recurrent stone-formers, although at least a KUB likely needed before taking a patient to the OR.

One of the main issues seemed to be the practicality of universally applying the “ultrasound first” approach. Many institutions do not have ultrasound readily available during night or weekend hours.

ER folks disagreed, and thought that point-of-care ultrasound could be easily adopted.

@soph_cash suggested urologists be the ones to perform ultrasound. Although an important skill to learn, the idea was quickly put to rest.

Author Rebecca Smith-Bindman made a brief appearance in support of the evidence in the study.

Coincidentally, the twitter-based nephrology journal club, #nephjc, discussed the same article this month. @hswapnil tweeted a useful chart comparing radiation doses (think about this next time you eat a banana) https://www.xkcd.com/radiation/

Although the conclusions among nephrologists were similar, @uretericbud said it best:

Overall, the consensus seemed to be that the paper presents good evidence for starting with ultrasound in the ED but applying this in all institutions may be difficult. Ultrasound also has limited use for urologists who are focused on stone treatment rather than catastrophic misses. Finally, some concluding thoughts from participants:

Thank you to all the tweeps over the last two years who have provided knowledge, insight, and a healthy dose of comedy to make #urojc such a huge success. Plugging an idea floated by @CanesDavid…

This month’s best tweet prize was sponsored by one beautiful thing vintage furniture.

Lastly, here are the symplur analytics for the month.

Ariel Fredrick is a PGY-2 urology resident at Lahey Hospital in Burlington, Massachusetts.

 

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