Tag Archive for: Prostate cancer

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Article of the week: “Twist” of fate: epithelial–mesenchymal transition (EMT) markers predict recurrence in prostate cancer

Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

Expression patterns of epithelial–mesenchymal transition markers in localized prostate cancer: significance in clinicopathological outcomes following radical prostatectomy

Hosny M. Behnsawy, Hideaki Miyake, Ken-Ichi Harada and Masato Fujisawa

OBJECTIVE

• To analyse the expression patterns of multiple molecular markers implicated in epithelial–mesenchymal transition (EMT) in localized prostate cancer (PC), in order to clarify the significance of these markers in patients undergoing radical prostatectomy (RP).

PATIENTS AND METHODS

• Expression levels of 13 EMT markers, namely E-cadherin, N-cadherin, b-catenin, g-catenin, fibronectin, matrix metalloproteinase (MMP) 2, MMP-9, Slug, Snail, Twist, vimentin, ZEB1 and ZEB2, in RP specimens from 197 consecutive patients with localized PC were evaluated by immunohistochemical staining.

RESULTS

• Of the 13 markers, expression levels of E-cadherin, Snail, Twist and vimentin were closely associated with several conventional prognostic factors.

• Univariate analysis identified these four EMT markers as significant predictors for biochemical recurrence (BR), while serum prostate-specific antigen, Gleason score, seminal vesicle invasion (SVI), surgical margin status (SMS) and tumour volume were also significant.

• Of these significant factors, expression levels of Twist and vimentin, SVI and SMS appeared to be independently related to BR on multivariate analysis

• There were significant differences in BR-free survival according to positive numbers of these four independent factors. That is, BR occurred in four of 90 patients who were negative for risk factors (4.4%), 21 of 83 positive for one or two risk factors (25.3%) and 19 of 24 positive for three or four risk factors (79.2%).

CONCLUSION

• Measurement of expression levels of potential EMT markers, particularly Twist and vimentin, in RP specimens, in addition to conventional prognostic parameters, would contribute to the accurate prediction of the biochemical outcome in patients with localized PC following RP.

 

Read Previous Articles of the Week

Editorial: The promise of EMT-associated biomarkers in a clinical setting

Emily A. Matuszak  and Natasha Kyprianou
Departments of Toxicology, Urology and Biochemistry, University of Kentucky College of Medicine, Lexington, KY, USA

Radical prostatectomy is among the most successful treatment modalities for patients exhibiting clinically localized prostate cancer. Despite this, roughly one-third of all radical prostatectomy patients will experience biochemical recurrence following prostatectomy. Curing prostate cancer requires a greater understanding of distinct biological events that differentiate prostate cancer from advanced life-threatening disease. Thus, a current challenge facing the clinical management of prostate cancer is the need for novel prognostic biomarkers capable of predicting biochemical recurrence to direct therapeutic interventions at earlier disease stages.

The oncogenic epithelial–mesenchymal transition (EMT) plays a critical role in metastatic prostate cancer progression [1]. EMTs engender coordinated molecular and genetic events which provoke phenotypic transformations that are indicative of the acquisition of mesenchymal characteristics which yield altered cellular behaviours [2]. Such altered behaviours may include but are not limited to enhanced migratory capability, increased invasive capacity, heightened resistance to apoptosis and conferred stem-like properties [3,4]. Conversion of an epithelial-derived prostate cancer cell to a more mesenchymal-like state has recently been implicated in prostate tumourigenesis as a mechanism facilitating the progression to metastatic castration-resistant disease [5].While alterations in the expression profiles of numerous EMT-associated transcriptional regulators and their molecular targets have served as biomarkers for studying EMT programmes, less is known about the contributions of EMTs in the emergence of treatment failure and tumour recurrence. Recently, EMT has been suggested to be a programme involved in metastatic disease progression that may also profoundly influence therapeutic outcomes amongst patients. Thus, it may be advantageous to develop predictors for risk assessment among prostate cancer patients that include specific EMT-associated markers in clinical evaluations.

Despite our current lack of knowledge regarding the clinicopathological significance of EMT, the potential value of an EMT marker signature as a prognostic indicator of biochemical recurrence among prostate cancer patients has emerged with some promise. Behnsawy et al. establish an initial path towards estimating the clinical value of assessing EMT marker levels in tandem with conventional clinicopathological prognostic factors in radical prostatectomy specimens from patients with organ confined prostate cancer, without any neoadjuvant therapy. Their evaluation follows a robust profile and results intriguingly reflect a pattern that may facilitate prediction of biochemical recurrence among patients. Using an exhaustive immunohistochemical analysis, the expression patterns of 13 EMT markers were evaluated in 197 radical prostatectomy specimens of which the expression levels of two EMT-associated markers, Twist and vimentin, were the most promising factors for such predictions.

The novel aspect and translational significance of this study are both reflected in the homogeneity of the patient population, in terms of localized organ confined disease. It represents an initial step towards recognizing an expression signature for specific EMT-associated factors in the therapeutic outcome of localized prostate cancer, but not disease progression. While the clinical impact of the reported findings may not be fully apparent, one may begin to speculate the promise of incorporating EMT-associated biomarkers in a clinical setting to facilitate diagnosis, prognosis and/or directing treatment strategies among patients. Primary endpoints of acquisition of an EMT phenotype following androgen axis targeting treatment must be clearly defined in the design of future clinical trials for the treatment of prostate cancer patients, with caution being given to selection of biopsy specimens vs radical prostatectomy specimens at an ‘optimal’ EMT window and in order to mitigate bias in tissue sampling resulting from long duration of therapeutic intervention. Control groups will provide valuable biological material to identify alternative mechanisms of treatment resistance (MAPK signalling). The statistical power in the relatively large cohort analysed enhances our confidence in considering the EMT landscape as an attractive platform for prediction of therapeutic response in future clinical trials. The concern, however, of whether improved prediction of biochemical recurrence by EMT profiling in pretreatment biopsies justifies its integration in the clinicopathological parameters (Gleason score, PSA) remains. Thus high expectations and much promise surround the pathological exploitation of EMT biomarkers (as signatures) in identifying profiles of tumour aggressiveness and providing a significant contribution in our quest towards the development of personalized therapies in prostate cancer patients with advanced disease.

References
1 Matuszak E, Kyprianou N. Androgen regulation of epithelial–mesenchymal transition in prostate tumorigenesis. Expert Rev Endo Metab 2011; 6: 469–82
2 Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial–mesenchymal transition in development and disease. Cell 2009; 139: 871–90
3 Polyak K, Weinberg RA. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer 2009; 9: 265–73
4 Kalluri R, Weinberg R. The basics of epithelial–mesenchymal transition. J Clin Invest 2009; 119: 1420–8
5 Tanaka H, Kono E, Tran CP et al. Monoclonal antibody targeting of N-cadherin inhibits prostate cancer growth, metastasis and castration resistance. Nat Med 2010; 16: 1414–20

What prophylactic steps should we take to prevent DVT/PE after RARP?

Deep vein thromboses (DVT) and pulmonary embolism (PE) are rare, but potentially devastating, complications of major pelvic surgery. We have performed more than 1000 robot assisted radical prostatectomy (RARP) procedures in Central London (Lessons learned from 1000 RARP operations BJUI 2013;111(1):9-10.) and to date encountered just a couple of DVTs, as well as a single, non-fatal instance of PE. However, in the case of one of us (RK), a close relative passed away as a result of a PE 10 days after a routine hip replacement performed in Oxford, a very sad event which highlighted the very negative impact on the family of this preventable surgical complication.

Guidance from NICE recommends that evidence-based steps be taken to reduce the risk of venous thromboembolism (VTE). Failure to do so therefore renders us open to criticism if a DVT, or worse a PE, does develop. On the other hand, pelvic haematoma and haematuria are troublesome complications of RARP, the risks of which may be exacerbated by anticoagulation.

What therefore should we be doing to reduce the risk of before and after laparoscopic pelvic surgery? Few would disagree that TED stockings should be worn before and after surgery, but how long should they be retained, as many patients do find them rather uncomfortable? Calf compression boots during surgery and for 12 hours or so post-operatively should also be standard practice.

More contentious is the duration of use of low molecular weight heparin (LMWH). Some surgeons use a single dose immediately prior to the operation; we have used 5000 Units of Clexane post-operatively for 2-3 days. Orthopaedic surgeons are increasingly continuing LMWH for 28 days at home after joint replacement surgery, which carries a significant risk of VTE. Should we follow their lead? A simpler alternative from the patients’ viewpoint is daily use of one of the new oral anti-coagulants such as dabigatran.

Perhaps the most sensible approach clinically is to perform a risk assessment of all RALP candidates pre-operatively. A calf compression device and TED stockings should be used for all patients, together with LMWH, while in hospital. Those considered especially at risk with, for example, a BMI >30 (Becattini CA) (See Box 1), should usually go home for a month with either LMWH injections or daily oral dabigatran, or equivalent oral anticoagulant agent.

We would be most interested in the views, experiences and current practice of the readers of this piece. Please do post your own response.

 

Roger Kirby, Ben Challacombe and Prokar Dasgupta
The Prostate Centre, London W1G 8GT and Guy’s Hospital, King’s College London, King’s Health Partners

 

Comments on this blog are now closed.

Ten stories of 2012, part II

Thanks for all the helpful input regarding my first blog post. Constructive criticism is always helpful, especially if I am to get better at this.

If you haven’t read it, part 1 is here.

So, in no particular order, part 2 of 2:

+ Metastatic prostate cancer – it’s getting complicated…

2012 was a year of hope for metastatic prostate cancer patients.  First, Enzalutamide (also known as MDV3100), in the context of a phase III RCT, was shown to prolong the survival of men with metastatic prostate cancer after chemo. And just when we thought the year was over, Abiraterone, which was previously shown to improve survival in patients with metastatic prostate cancer after chemotherapy, was found to be beneficial even in chemo-naive patients. All this translates into more complicated algorithms for castrate-resistant prostate cancer.  That said, my question is the following: what happens if these drugs are effective at treating localized prostate cancer? It seems that some medical oncologists are trying to figure that out. Prostatectomists, murky waters lie ahead! Oh wait, I’m part of that group.

+ The changing landscape of surgical education

Times They Are a-Changin’. Residents are working less but don’t sleep more. 16-hour work day restrictions. More women are admitted into surgical fields. Protected nap (sleep) time during calls. Residents not covering floor consults during the day (those are actually the rules where I work). Most trainees now value quality of life above anything else, possibly even the quality of their training (do read this beautiful piece by a Urologist in JAMA: Considering Life Before Lifestyle. Yet, the amount of knowledge a resident needs to consolidate during residency is at least 10-fold greater than what the old geezers had to learn back in the days (the current Campbell-Walsh is 134 chapters, 4320 pages). Whether or not you agree with any of the above (which is irrelevant anyways, because it’s happening whether you like it or not), attending surgeons and urologists are finding it hard to adapt or understand. “Honey, things were much harder back when I was a resident…” How do we evolve as a sub-specialty without compromising surgical education (or lengthening residency)? Status quo is not an option.

+ Radiotherapy for prostate cancer – what’s up with that?

A nice observational study from Sheets et al in the JAMA thematic issue on Comparative Effectiveness Research showed that “use of IMRT compared with conformal radiation therapy was associated with less gastrointestinal morbidity and fewer hip fractures but more erectile dysfunction“. Yet, Jacobs et al, using the same dataset and almost the same study years, showed that the risks of salvage therapy and complications are comparable between the two modalities, for most patients. And let’s not get started about proton-beam therapy. Whilst this costly approach is gaining precedence in the treatment of localized prostate cancer, severe doubts exist regarding its efficacy. The bombshell: another observational study from Yale, based on Medicare data: “Although proton radiotherapy is substantially more costly than IMRT, there was no difference in toxicity in a comprehensive cohort of Medicare beneficiaries with prostate cancer at 12 months post-treatment“. Ouch.  To be perfectly honest (sometimes I’m told I should shut up), it would be hypocrisy for robotic surgery fanboys to condemn proton beam therapy right now. As we all know, it took years before convincing observational data showed that robotic radical prostatectomy is better than open, at some levels. Maybe someone responsible will actually perform a prospective comparative effectiveness assessment between these modalities. As an avid blogger suggests, maybe the proton beams and the robots should fight for world domination.

+ Urology at the forefront of the social media revolution

As a group, we should be proud of how we embraced social media in 2012. In the field of medicine, where anything novel is usually met with smirk and mockery (see: surgery, robot-assisted), social media has been surprisingly well received, thanks to a tight-knit community of twitter champions (if you’re new to twitter, you should definitely follow urologymatch.com’s list of key opinion leaders (KOLs) in Urology. Moreover, the first International Urology Journal Club was held in November 2012 and has been a global success ever since. I’m sure that 2012 was only the start. It will be exciting to see the role of social media in upcoming international meetings such as the EAU, AUA and BAUS. Virtual high-five everyone!

+ Be inspired.

OK, so this one has nothing to do with Urology, or Medicine for that matter. Here’s a toast to the events that shook 2012, and let’s hope that 2013 will be a great year!

 

 

Quoc-Dien Trinh
@qdtrinh

 

Quoc-Dien Trinh is a minimally-invasive urologist and co-director of the Cancer Prognostics and Health Outcomes Unit. His research focuses on patterns of care, costs and outcomes in prostate cancer treatment.

 

Comments on this blog are now closed.

 

Twitter: my #eurekamoment #pennydrops #babyvomit

I remember distinctly when the penny dropped for me. It was about 2am on a warm summer’s night in early January 2012 (apologies to those of you shivering in the Northern Hemisphere). I had my one-week old son in one arm, swinging between sleeping and spewing, and an iPad in my other hand, providing distraction between nappy changes and feeds. The sleep-deprivation had dulled my senses considerably and my brain was capable of no more than light reading.

It was then I read a piece in the New York Times online about the power of Twitter in medical communication. Previously, I thought Twitter was the domain of Lady Gaga, Justin Bieber, Kim Kardashian (Kim who?) and various narcissistic cricket and football players. It seemed like puerile nonsense for a generation that I no longer belonged to. However, reading this opinion piece made me think again. It was clear that there is a whole generation of significant academic clinicians, researchers and publishers who have embraced social media and who use Twitter, in particular, to disseminate their work with a speed and reach that is simply unachievable through any other medium. I was struck by various examples of how key scientific publications are first flagged on Twitter and how within hours, responses are made by key opinion leaders and these responses are again disseminated rapidly around the Twittersphere. And although none of the examples were based around urology, it was clear to me that oncologists and surgeons were getting on board the social media rollercoaster.

So between nappy changes and having wiped some baby vomit off my iPad, I logged onto Twitter and created a username. I searched for prostate cancer and urology and quickly found my way to a few key resources and super-users who seemed to have a very active Twitter presence and who were tweeting content that immediately appeared of interest to me. Within a few minutes I had identified a few highly valuable Twitter users to follow and within their lists of followers and those who they were following, I quickly built up a useful stream of tweets dropping into my timeline. And then of course, a few of these Twitterers started following me back, which was mildly exciting. Within a few days and having posted a few tweaks, I began to feel part of the Twittersphere.

As the weeks went by, I continued to be astounded by just how fast information travels on Twitter. While I get emails with the table of contents for the various journals that I subscribe to, these only drop in my inbox every few weeks. Also, because there are a number of significant journals that I do not subscribe to (non-urological mostly), there are many papers published out there that do not come immediately to my attention. Depending on which Twitter sites you follow, all key papers related to your area of interest find their way into your timeline instantaneously as soon as they are published. Not just that, very interesting comment from others also gets to you very quickly. For example, key findings in prostate cancer tend to be picked up by the major US news sites who then invite comment from key leaders in major cancer centres. A typical example is that of the PSA screening recommendations made by the United States Preventive Services Taskforce in June 2012, which provoked huge controversy. Twitter came to life and key opinion leaders such as Matt Cooperberg (@cooperberg_ucsf) helped drive the conversation through Twitter and blogs (e.g.The Huffington Post blog) at lightning speed. These comments get tweeted out and responses to these comments also get blogged and within hours of a paper being published you have news of the paper, expert comment and wider reaction…… all in 140 characters or less!

And while none of us have much time in the day to add an extra task, I find that waiting for my coffee in the morning or while the resident puts an arterial line in my next patient, there are a few spare moments in the day where the Twitter app on my iPhone comes to life. Twitter is perfectly suited to the smart phone user and that is where the majority of tweets around the world are generated from. It is also perfectly suited for one of the other very exciting areas in which I have seen Twitter play a very useful role – that of conferencing. At the EAU in Paris, a small but energetic group of Twitter users started tweeting content from various sessions at this large meeting and started engaging with other Twitter users around the world. For me, I believe conferencing is about to be transformed by the power of social media but more about that soon.

For now, at the new BJUI, we want to grow the audience and get you all to join the conversation. Through Twitter, blogging, Facebook, YouTube and other social media platforms, we are building for the future of communication in urology. The next generation of trainees will be deeply embedded in all of these platforms and will expect to be engaged through them. We are entering a new generation of medical communication – come join the conversation.

Declan Murphy
@declangmurphy

 

Declan Murphy is Honorary Clinical Associate Professor at the Department of Surgery, University of Melbourne, St Vincent’s Hospital and Director of Robotic Surgery at the Peter MacCallum Cancer Centre. He had previously been consultant urological surgeon at Guys & St Thomas’ NHS Foundation Trust in London.

 

Comments on this blog are now closed.

Article of the Week: The New Partin Tables

Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying blog written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video of John Eifler and Alan Partin discussing their paper.

If you only have time to read one article this week, it should be this one.

 

An updated prostate cancer staging nomogram (Partin tables) based on cases from 2006 to 2011

John B. Eifler, Zhaoyang Feng, Brian M. Lin, Michael T. Partin, Elizabeth B. Humphreys, Misop Han, Jonathan I. Epstein, Patrick C. Walsh, Bruce J. Trock, Alan W. Partin

OBJECTIVE

• To update the 2007 Partin tables in a contemporary patient population.

PATIENTS AND METHODS

The study population consisted of 5,629 consecutive men who underwent RP and staging lymphadenectomy at the Johns Hopkins Hospital between January 1, 2006 and July 30, 2011 and met inclusion criteria.

• Polychotomous logistic regression analysis was used to predict the probability of each pathologic stage category: organ-confined disease (OC), extraprostatic extension (EPE), seminal vesicle involvement (SV+), or lymph node involvement (LN+) based on preoperative criteria.

• Preoperative variables included biopsy Gleason score (6, 3+4, 4+3, 8, and 9–10), serum PSA (0–2.5, 2.6–4.0, 4.1–6.0, 6.1–10.0, greater than 10.0 ng/mL), and clinical stage (T1c, T2c, and T2b/T2c).

• Bootstrap re-sampling with 1000 replications was performed to estimate 95% confidence intervals for predicted probabilities of each pathologic state.

RESULTS

• The median PSA was 4.9 ng/mL, 63% had Gleason 6 disease, and 78% of men had T1c disease.

• 73% of patients had OC disease, 23% had EPE, 3% had SV+ but not LN+, and 1% had LN+ disease. Compared to the previous Partin nomogram, there was no change in the distribution of pathologic state.

• The risk of LN+ disease was significantly higher for tumors with biopsy Gleason 9–10 than Gleason 8 (O.R. 3.2, 95% CI 1.3–7.6).

• The c-indexes for EPE vs. OC, SV+ vs. OC, and LN+ vs. OC were 0.702, 0.853, and 0.917, respectively.

• Men with biopsy Gleason 4+3 and Gleason 8 had similar predicted probabilities for all pathologic stages.

• Most men presenting with Gleason 6 disease or Gleason 3+4 disease have <2% risk of harboring LN+ disease and may have lymphadenectomy omitted at RP.

CONCLUSIONS

• The distribution of pathologic stages did not change at our institution between 2000–2005 and 2006–2011.

• The updated Partin nomogram takes into account the updated Gleason scoring system and may be more accurate for contemporary patients diagnosed with prostate cancer.

Erratum:

A typographical error was identified in Table 2, for the cell corresponding to the probability for EPE in a man with clinical stage T1c, PSA >10, and biopsy Gleason 4+3. The cell should read “38 (32-45)” rather than “28 (32-45).” Also, in the third paragraph of the Results section, the fourth sentence should be changed to “In contrast, the predicted risk of LN+ is no more than 3% for T1c tumours with biopsy Gleason score <9 for an PSA below 10.”

Editorial: What have we learned from the Partin table update?

The controversies surrounding a physician’s best treatment strategy advice to an individual patient with clinically localized prostate cancer create a continuing need for advanced statistics. Historically, the Partin tables [1] were one of the first statistical tools that physicians and patients found readily usable. The tables have been updated and always focused on prediction of pathologic stage from standard clinical variables. The next commonly cited/used tool was the Kattan nomogram [2] that carried the prediction the next step to the endpoint of biochemical relapse. By 2008, Shariat et al catalogued over 100 predictive tools published from 1966 to 2007 on various endpoints of prostate cancer [3].

 

 

 

What have we learned from this update of the Partin tables?

  1. The pre-operative grade distribution has shifted up slightly with no change in prostatectomy grade/stage distribution. The authors discuss possible causes such as changes in interpreting the Gleason scoring system, shifts in selection for surgery away from lower grade patients, and a possible plateau in stage migration.
  2. The tables have split off Gleason 3+4, 4+3, 8, and 9–10, and found the latter significantly more aggressive, while Gleason 4+3 and 4+4 are more similar. Gleason 9–10 must have a pattern 5 component >5% and may therefore have more aggressive biology. On the other hand, two cases of prostate cancer may have identical volumes of 4 pattern, but if one adds additional 3 pattern, that additional tumour foci paradoxically lowers the sum to 7, but perhaps not the risk of non-organ confined stage.
  3. In the past, the tables were commonly used to predict pT3 stage, with possible change in management away from surgery as that risk increased. Clearly the literature on surgery for higher risk disease has matured, and augmented by the adjuvant/salvage radiation literature such that it is less likely to use the tables for this reason any more. On the other hand, prediction of N1 disease for the purpose of omitting a lymph node dissection remains a useful tool. In this update, using a <2% cut-off you would essentially omit all node dissections in Gleason 6 with PSA < 10 and cT1c/cT2a, while continuing with a dissection for any dominant Gleason 4 pattern. It is noteworthy that this experience was largely based upon standard templates, and those advocating extended templates will find these N1 rates too low. Indeed, when our center adopted the extended template using a robotic technique, the N1 rate for high-risk disease was 39% and 9% for intermediate risk [4]. Moving forward, what tools do we need to provide useful statistics to our patients? Updating old tools with more contemporary patient cohorts is certainly a worthy exercise. Multicentre study based tools will be required for endpoints such as positive surgical margins, quality of life, biochemical recurrence, and other endpoints that may be significantly affected by the experience of the treating physician. Beyond this, the next step should be adaptive nomograms that update in real time rather than en masse every 4–5 years [5].

John W. Davis
Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

References
1 Eifler JB, Feng Z, Lin BM et al. An updated prostate cancer staging nomogram (Partin tables) based on cases from 2006 to 2011. BJU Int 2013; 111: 26–33
2 Kattan MW, Eastham JA, Stapleton AM et al. A preoperative nomogram for disease recurrence following radical prostatectomy for prostate cancer. J Natl Cancer Inst 1998; 90: 766–71
3 Shariat SF, Karakiewicz PI, Roehborn CG, Kattan MW. An updated catalog of prostate cancer predictive tools. Cancer 2008; 113: 3075–99
4 Davis JW, Shah JB, Achim M. Robot-assisted extended pelvic lymph node dissection (PLND) at the time of radical prostatectomy (RP): a video-based illustration of technique, results, and unmet patient selection needs. BJUI 2011; 108: 993–8
5 Vickers AJ, Fearn P, Scardino PT et al. Why can’t nomograms be more like Neflix? Urology 2010; 75: 511–3

John Eifler and Alan Partin discuss their article

An updated prostate cancer staging nomogram (Partin tables) based on cases from 2006 to 2011.

John B. Eifler, Zhaoyang Feng, Brian M. Lin, Michael T. Partin, Elizabeth B. Humphreys, Misop Han, Jonathan I. Epstein, Patrick C. Walsh, Bruce J. Trock and Alan W. Partin
James Buchanan Brady Urological Institute and the Department of Urology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

Objective

  • To update the 2007 Partin tables in a contemporary patient population.

Patients and Methods

The study population consisted of 5,629 consecutive men who underwent RP and staging lymphadenectomy at the Johns Hopkins Hospital between January 1, 2006 and July 30, 2011 and met inclusion criteria.

  • Polychotomous logistic regression analysis was used to predict the probability of each pathologic stage category: organ-confined disease (OC), extraprostatic extension (EPE), seminal vesicle involvement (SV+), or lymph node involvement (LN+) based on preoperative criteria.
  • Preoperative variables included biopsy Gleason score (6, 3+4, 4+3, 8, and 9–10), serum PSA (0–2.5, 2.6–4.0, 4.1–6.0, 6.1–10.0, greater than 10.0 ng/mL), and clinical stage (T1c, T2c, and T2b/T2c).
  • Bootstrap re-sampling with 1000 replications was performed to estimate 95% confidence intervals for predicted probabilities of each pathologic state.

Results

  • The median PSA was 4.9 ng/mL, 63% had Gleason 6 disease, and 78% of men had T1c disease.
  • 73% of patients had OC disease, 23% had EPE, 3% had SV+ but not LN+, and 1% had LN+ disease. Compared to the previous Partin nomogram, there was no change in the distribution of pathologic state.
  • The risk of LN+ disease was significantly higher for tumors with biopsy Gleason 9–10 than Gleason 8 (O.R. 3.2, 95% CI 1.3–7.6).
  • The c-indexes for EPE vs. OC, SV+ vs. OC, and LN+ vs. OC were 0.702, 0.853, and 0.917, respectively.
  • Men with biopsy Gleason 4+3 and Gleason 8 had similar predicted probabilities for all pathologic stages.
  • Most men presenting with Gleason 6 disease or Gleason 3+4 disease have <2% risk of harboring LN+ disease and may have lymphadenectomy omitted at RP.

Conclusions

  • The distribution of pathologic stages did not change at our institution between 2000–2005 and 2006–2011.
  • The updated Partin nomogram takes into account the updated Gleason scoring system and may be more accurate for contemporary patients diagnosed with prostate cancer.

Eifler JB, Feng Z, Lin BM, et al. An updated prostate cancer staging nomogram (Partin tables) based on cases from 2006 to 2011. BJU Int 2013; 111: 26–33.

Step-by-Step. Ergonomic use of the fourth arm

Ergonomic use of the fourth arm to oversew the dorsal vascular complex (DVC) during robot-assisted laparoscopic prostatectomy (RALP)

Omer Karim, Amrith Rao, Emma Marsdin, Rajesh Kavia, Arie Parnham, Hanif Motiwala and Marc Laniado
Centre for Robotics and Minimally Invasive Surgery,Wexham Park Hospital, Slough, Berkshire, UK

Objective

• To demonstrate an ergonomic fourth arm technique to oversew the dorsal vascular complex (DVC) during robot-assisted laparoscopic prostatectomy (RALP).

Patients and Methods

• Balloon of a Foley catheter inflated in the bulbar urethra.
• Fourth arm cranial traction via suture in the tip of the catheter.
• DVC oversewn under direct vision.

Results

• Oversew of DVC with minimal patient-side surgical assistance.
• About a 50% reduction in apical positive margin rate.

Conclusion

• A useful, ergonomic method of oversewing the DVC
during RALP.

Karim O, Rao A, Marsdin E, et al. Ergonomic use of the fourth arm to oversew the dorsal vascular complex (DVC) during robot-assisted laparoscopic prostatectomy (RALP). BJU Int 2013; 111: 179–180.

Inadvertent injury to an incidental ectopic ureter in a completely duplicated collecting system during open radical perineal prostatectomy

We present the diagnosis and management of a man with clinically localised prostate cancer and a complete duplication of the right collecting system associated with an asymptomatic upper pole ectopic ureter, that was inadvertently injured during open RPP.

Authors: Miguel Suhady (MS) Cabalag1, Henry Han-I (HH) Yao1, Gideon Adam (GA) Blecher1, Antonio (A) DeSousa1, Diana (D) Tran2

1 Department of Urology, Ballarat Base Hospital, Ballarat, Victoria, Australia
2 Department of Radiology, Royal Melbourne Hospital, Melbourne, Victoria, Australia

Corresponding Author: Richard (R) McMullin,  Consultant Urologist, Ballarat Base Hospital, Drummond Street North  Ballarat VIC 3350, Ballarat, Victoria, Australia E-mail: [email protected]

 

Abstract
 
It is rare for embryologic abnormalities of the urinary tract to present in adulthood, especially as an incidental finding post radical perineal prostatectomy (RPP). We present the incidental diagnosis and subsequent management of a 68 year old man with clinically localised prostate cancer and a complete duplication of the right collecting system associated with an asymptomatic upper pole ectopic ureter, that was inadvertently injured during open RPP.

 

Introduction
 
With the earlier detection of clinically localised prostate cancer using prostate specific antigen (PSA) testing, it has become routine not to perform extensive staging investigations to avoid unnecessary tests. This approach may lead to rare unforeseen post-operative complications in patients with asymptomatic congenital anomalies of the urinary tract. We report the case of a 68 year old man who presented with persistent urinary extravasation from his surgical wound following RPP. Subsequent CT intravenous urogram demonstrated an incidental complete duplication of the right collecting system and an injured right upper pole ectopic ureter. To our knowledge, there are only four cases reported in the literature of ectopic ureters found incidentally in men undergoing radical prostatectomy for prostate cancer (1-4), and we describe the first case reported during RPP.

 

Case Report
 
A 68 year old asymptomatic man initially presented with an incidental elevated PSA of 4.8 ng/ml (12% free) detected on routine testing. The patient otherwise had no significant past medical history. On digital rectal examination, the prostate was mildly enlarged and firm but with no palpable nodules bilaterally. Trans-rectal ultrasound (TRUS) of the prostate with concurrent 12 core guided biopsies, revealed no suspicious areas and an estimated prostate volume of 60 cm3. Histopathology showed a 2mm focus of Gleason 6 (3+3) prostate adenocarcinoma, which was only detected following further immunohistochemical staining. An active surveillance approach with six monthly PSA tests was initially adopted given the very low volume of malignancy. Over the next 18 months, the PSA gradually rose to 8.2 ng/ml whereby a repeat TRUS guided biopsy revealed prostate adenocarcinoma with Gleason 6 (3+3) in 33% of 1 core obtained from the right lateral prostate (clinical stage T1c).
Following patient counselling, a radical nerve-sparing perineal prostatectomy was performed using a previously described technique (5). A routine pre-operative rigid cystoscopy revealed a normal urethra and bladder with two appropriately located ureteric orifices. Surgery went as planned and a 16Fr two-way silicone indwelling catheter was inserted into the bladder intra-operatively. The urethral anastomosis was subsequently checked to ensure a watertight seal and a tube drain was also inserted through a separate stab incision into the perineum. Pelvic lymphadenectomy was not performed due to the patient’s low risk pathology. The final pathology demonstrated a Gleason 7 (3+4) adenocarcinoma, localised predominantly to the right lower zone involving approximately 15% of total prostatic volume. Lymphovascular invasion was absent and the surgical margins were clear.
Early post-operative recovery was uneventful and the drain tube was removed on post-operative day (POD) 2. A routine trial of void 2 weeks post surgery resulted in a persistent urine leak from the apex of his perineal wound, which was exacerbated by urination. Of note, the patient remained pain free and afebrile throughout the post-operative period. This was initially suggestive of an anastomotic leak and therefore the indwelling urinary catheter was re-inserted. However, a cystogram did not show any extravasation of contrast (Figure 1) and the leak persisted through the apex of the wound, so the re-introduced urinary catheter was removed.
Figure 1. Post-operative retrograde cystogram showing no anastomotic leakage

 

 

Subsequent computed tomography (CT) intravenous urogram demonstrated a complete duplication of the right collecting system with an ectopic right upper pole ureter (Figure 2a and 2b), the distal end of which could not be properly visualised.

 

Figure 2a.  Coronal view of the CT intravenous urogram showing the right lower pole ureter (LPU) and the right upper pole ectopic ureter (UPEU).

 

 

Figure 2b. 3D reconstruction of the coronal CT-intravenous urogram showing the orthotopic insertion of the right lower pole ureter (LPU) into the bladder (solid arrow), the tortuous right upper pole ectopic ureter (UPEU, dotted arrow). Note an indwelling urinary catheter is in situ.

 

 

There was also a fistulous tract originating from the ectopic ureter, draining into the perineum (Figure 3). The patient subsequently developed right-sided epididymo-orchitis, which was successfully treated with intravenous gentamicin and amoxicillin.

 

Figure 3. Coronal view of the CT intravenous urogram demonstrating the right upper and lower pole renal moieties, as well as a fistulous tract (solid arrow) originating from the ectopic ureter into the perineum on the right side (dotted arrows). 

 

Management
 
The patient subsequently underwent a rigid cystoscopy and a right retrograde pyelogram, which demonstrated a non-dilated right ureter draining into a lower renal moiety, producing a ‘drooping lily’ type image of the right kidney (Figure 4).

 

Figure 4. Right retrograde pyelogram demonstrating the characteristic ‘drooping lily’ image of the lower renal moiety. 

 

 

After patient counselling, the decision was then made to perform an open right ureteric reimplantation. Intra-operatively, two ureters were identified in the retroperitoneum adjacent to the bifurcation of the right common iliac vessel. The lateral ureter was entered via a small stab incision and dye was injected. This dye was noted to be draining out of the indwelling catheter and therefore this was thought to be the normal ureter that was draining into the bladder. The medial ureter was also pierced and dye was injected, but the dye was not detected in the bladder. Thus, this was thought to be the ectopic ureter, most likely to have been injured during the RPP. Given the close proximity of the bladder to the ectopic ureter, a uretero-vesical anastomosis was performed. The distal ectopic ureter was spatulated and a cystotomy was made at a corresponding site. A 6Fr 26 cm ureteric stent was passed through the ectopic ureter over a guide wire up to the right kidney, and the distal end was placed through the cystotomy. Using four, 4-zero vicryl sutures in an interrupted fashion, the ureter was securely implanted onto the bladder with good mucosal apposition. A pelvic drain tube was placed adjacent to the newly formed uretero-vesical anastomosis. There were no peri-operative complications, the drain was removed on POD 4 and the patient was discharged home on POD 6. A flexible cystoscopy was performed approximately 4 weeks after to remove the ureteric stent. Repeat CT intravenous urogram performed 2 months post re-implantation demonstrated complete duplication of the right collecting system with double ureters in which contrast drained normally into the bladder. Importantly, it did not show any hydronephrosis bilaterally, no perineal collection nor any leak from the right renal tract (Figure 5).

 

Figure 5. Coronal view of the CT intravenous urogram post uretero-vesical anastomosis of the right upper pole ectopic ureter, showing resolution of the fistulous tract to the perineum.

 

 

Discussion
 
We report the case of a patient who was incidentally found to have a complete duplication of the right collecting system with an asymptomatic ectopic upper pole ureter that was inadvertently injured during a RPP. To our knowledge, this is the first case reported in the literature associated with such surgery.
A duplex system refers to a kidney with two pelvicalyceal systems within a single renal parenchyma, which may have either a single or bifid ureter (partial duplication), or two discrete ureters (complete duplication) (6).  Renal duplication is a relatively common congenital anomaly, with a reported prevalence of 0.3-6% (7). The majority of cases are detected during childhood, but up to 20% of patients remain asymptomatic into adulthood (8). In contrast, ectopic ureters are rare, with a reported incidence of 1 in 1900 (9). Ectopic ureters are more common in females and are usually associated with a duplicated collecting system, whereas they are typically associated with a single collecting system in men (10).The anatomic site of insertion of an ectopic ureter in a duplicated collecting system follows the Weigert-Meyer rule, whereby the upper pole ureter is more commonly ectopic and the lower pole ureter typically inserts into the trigone, or laterally and cranially to this structure. In 50-60% of patients, renal duplication is associated with vesicoureteric reflux, which may affect one or both ureters. Reflux is more common in the lower pole kidney (97%), while ureteroceles and ectopic ureters are commoner in the upper pole kidney (11).
The presentation of ectopic ureters depends on their site of insertion. Ectopic ureters inserting into the prostatic urethra typically present with urinary tract infections or lower urinary tract symptoms of urgency and frequency. Ectopic ureters inserting into a seminal vesicle, vas deferens or epididymis may present with epididymitis, chronic prostatitis, abdominal or pelvic pain, discomfort during ejaculation, constipation, or a large abdominal mass secondary to obstruction and hydronephrosis. Males with an ectopic ureter may also present with infertility (3).
In males, the majority of ectopic ureters (50%) insert into the prostatic urethra, and 33% into a seminal vesicle. The least common sites include the prostatic utricle and the vas deferens (12). Ectopic ureters in males almost never insert distal to the external sphincter, where it would present as urinary incontinence. One such case has been reported in the literature (13). Of note, this patient had no lower urinary tract symptoms prior to the RPP. It is likely that in this case, the upper pole ectopic ureter was transected during the bladder neck dissection at the level of the prostatic urethra.
There are multiple treatment options for the pathological ectopic ureter associated with a duplicated system, including ureteropyelostomy, heminphrectomy, ipsilateral ureteroureterostomy and common sheath reimplantation (14). An ureterovesical anastomosis was performed in this case due to the upper pole ectopic ureter being a distinct entity from the lower pole ureter, and because of its close proximity to the bladder.
Current guidelines do not recommend imaging of the prostate with CT or MRI for low risk disease prior to radical prostatectomy. Consequently, any asymptomatic congenital anomalies of the urinary tract will not be detected preoperatively. However, due to the rarity of such anomalies, as well as the expense and potential risk to patients, routine preoperative imaging to detect congenital abnormalities is not justifiable in this setting. In the retrospective study conducted by Costa et al, only 3 out of 254 (1.1%) surgical descriptions of nephroureterectomy samples showed anatomical variations of the collecting system, with all cases demonstrating ureteric duplications (15).
Of interest, given the established genetic association of duplex systems, the patient’s twin brother subsequently underwent a CT intravenous urogram, which did not demonstrate any evidence of a duplicated system or ectopic ureter.

 

Conclusion
 
Preoperative imaging may help detect asymptomatic congenital abnormalities of the urinary tract, enabling appropriate intraoperative management. However, given the rarity of such anomalies and the expense of imaging, extensive investigations prior to radical prostatectomy for the sole purpose of screening for congenital abnormalities is not justifiable. However, this case highlights the need to consider congenital anomalies of the urinary tract as a possible differential in peri-operative complications post radical prostatectomy.

 

References
 
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Date added to bjui.org: 23/05/2012
DOI: 10.1002/BJUIw-2011-145-web

 

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