Tag Archive for: LUTS

Posts

UroLift Takes Off From Down Under. The Potential Rewards When Engineers Bring You Into Their Inner Circle

At the American Urological Association meeting in San Antonio in May 2005, I was introduced to a four engineers from a small start up company called NC2 (New Company 2).  It had at that time been recently spun off from the medical device incubator company Exploramed.  They had no product and not even a prototype of a product that could possibly be used in humans but what they did have was a passion to make a difference, incredible ideas and a laptop computer. 

They had thought about the failings of existing mechanical treatments for LUTS/ BPH and the first that comes to your mind is prostatic stents.  No stent conforms perfectly to the shape of the prostatic urethra and there were the issues of encrustation of any elements of stent material that were exposed to the urine.  Rather than throw the baby out with the bathwater, they harnessed what was good about stents, which was the potentially immediate effects they could have on urinary function without associated destruction of tissue and that perhaps tailoring the radial expansion to just a few critical points rather than the entire length of the prostatic urethra could do the trick.

The original idea was that some sort of metallic disc could be placed outside the prostate capsule and one on the urethral side and between them, a non absorbable suture could be placed under tension and therefore draw open the prostatic urethra and defined sites.  How these engineers were to find a way of designing a delivery tool to do this had me a little skeptical at first but there seemed to be no doubt in their minds, even thought they had not yet worked it out, were going to find a way.  Their confidence, intellect and enthusiasm was infectious and you just felt like you wanted to be a part of this project.  It so turned out that the metallic discs would be replaced by linear metallic tabs which logically make for easier delivery.

So why involve Australians?  It is difficult to keep things under the radar and one way of doing so is to take the idea where it is less likely to be visible. Additionally, the data needed to be trustworthy and in a place where strong ethic committee governance structures exist. We make no illusion that for once, being Australian, gave us a clinical research opportunity from a company based in the US that would rarely be directed our way.

My Australian colleague, Dr Peter Chin was also brought in on the project.  Over the next few months, we did not hear anything but there was then an urgent call that ‘California was the place we ought to be’ so we literally dropped everything and headed over to Silicon Valley where we had the opportunity to use the first prototype of the device on human cadavers.  Whilst our travel costs were covered by NC2, we received no payment for our time spent during these exercises but remuneration was the last thing on our minds given the exciting path that the idea could potentially take.  Simultaneously, animal studies were being conducted and these demonstrated that the internal metallic tabs of the prosthesis would become covered by urothelium and in combination with the cadaveric work, provided a convincing argument to move forward with human clinical trials.

Putting on a brave face doing the first human Urolift case at Westmead Hospital in Sydney in December 2005

By December 2005, we were ready to conduct the first human trials.  We measured everything that could possibly move and it probably took close to 2 hours to perform the first case.  The initial prototype device used looked like it was literally built in somebody’s garage workshop but it was functional and confirmed proof in principle that a transurethral delivery system could deploy metallic tabs on the capsular side of the prostate and within the urethra that was connected by a tensioned suture. Through this, it created mechanical alteration to the anatomy of the prostatic urethra with positive influence on lower urinary tract symptoms.  From here, multiple clinical trials have been performed by the company that became known as Neotract Inc and as of 13 September 2013, the device received FDA approval.

It is enormous privilege to have played a role in product development from inception of an idea through to FDA approval.  These opportunities are rare and whilst healthy skepticism and caution should be applied to all ideas presented to you, if you are offered such an opportunity to take a side project, it could be a rewarding diversion from your daily clinical practice.  Financially, you will never recoup your time investment but the rewards of making a difference is priceless.

Shared passion for a project can go a long way.   This experience emphasizes the value of engineers interacting with clinicians to achieve a desired outcome and there is certainly room for of such interactions. Opportunities to embrace these relationships are out there and perhaps a good place to start is to become active in the Engineering and Urology Society which as a section of the Endourological Society meets each year at the AUA Annual Meeting.

 

Henry Woo is an Associate Professor of Surgery at the Sydney Adventist Hospital Clinical School of the University of Sydney in Australia. He has been appointed as the inaugural BJUI CME Editor. He is currently the coordinator of the International Urology Journal Club on Twitter. Follow him on Twitter @DrHWoo

Disclosure: Henry Woo has formerly been an investigator and advisor to Neotract Inc. He holds a small stock investment in the company.

Radiotherapy for Leukaemic infiltration of Prostate

We present an 81 year old gentleman with haematuria and LUTS who had TURP for his outflow symptoms. Radiotherapy is an excellent option for local symptom control as evidenced in this patient.

 

Authors: Venugopal S, Das.S,  Hamid BN, Doyle.G, Leggat H, Powell CS. Countess of Chester Hospital NHS Foundation Trust
 
Corresponding Author: Suresh Venugopal, Countess of Chester Hospital NHS Foundation Trust Email: [email protected]

Abstract
Haemopoietic malignant infiltration of the prostate is unusual. When present, it brings about the dilemma on the best approach to manage it. Usually, chronic lymphocytic leukaemia is an indolent process that waxes and wanes in its course and when present with lymphadenopathy and clinical symptoms would warrant treatment with chemotherapy. When organ confined, it has a more favourable course and would be amenable to local treatments.
We present an 81 year old gentleman with haematuria and LUTS who had TURP for his outflow symptoms. The histology had confirmed a malignant lymphocytic infiltration of the prostate and he had elevated lymphocytic count and peripheral blood marker study confirming chronic lymphocytic leukaemia. He was treated with radiotherapy of his prostate. His presenting WBC count was 19.2 and PSA was 4.41 and presently his white count is 10.3 and PSA is 1.77.  He was treated with 24 Gray external beam radiotherapy to the prostate.
As we encounter an aging population, we will be seeing more of these cancers with higher incidence in the elderly. Radiotherapy is an excellent option for local symptom control as evidenced in this patient.

 

Case Report
 
Presentation
 
An 81 year old gentleman had simultaneous referral to the haematologist for low haemoglobin and raised white count and the urologist for visible haematuria and LUTS. A digital rectal examination revealed a smooth, benign-feeling prostate with a normal age-specific PSA. A CT scan done to evaluate his haematuria had picked up a large mass in the pelvis. It was difficult to differentiate whether it was of bladder or prostate origin (Figure-1).

 

Figure 1: CT scan showing pre treatment pelvic mass (left) and post treatment pelvic mass (right).

 

Trans-urethral resection of the mass showed diffuse infiltration of the prostate gland by a malignant B-cell type lymphoid infiltrate. His peripheral blood markers for chronic lymphocytic leukaemia were positive. He did not have generalised lymphadenopathy, splenomegaly or B type symptoms of leukaemia.

 

Pathology
 
The trans-urethral resection chippings of prostate showed large foci of basal cell hyperplasia and extensive infiltration with monotonous population of small lymphoid cells (Figure-2).

 

Figure 2: Prostate tissue infiltrated by lymphocytes staining strongly for CD20 (left) and H&E staining showing sheets of monotonous lymphocytic infiltration of prostate (right). 

The abnormal lymphoid infiltrate stained positively for CD5, CD20, CD79a but was negative for CD3, CD10, BCL2 and BCL6. This is keeping in with a picture of Chronic Lymphocytic Leukaemia of Prostate. There was no evidence of high grade PIN or adenocarcinoma of prostate.

 

Radiotherapy
 
In view of his symptomatic haematuria and potential for the lesion to cause local symptoms of persistence of haematuria and possible obstruction of adjacent structures, he was considered for radiotherapy after due discussion at the multidisciplinary team meeting. The pros and cons of the treatment was discussed with the patient and he opted to have the treatment. He received standard 24 Gray in 12 fractions for low grade lymphoma of the prostate (1).

 

Follow-up
 
He has since been regularly followed up at the urology clinic for his lower urinary tract symptoms with a flow rate and rectal examination on the six monthly visits as well as a yearly PSA test. He does not have any lower urinary tract symptoms. His six monthly follow-up in the haematology clinic for his Chronic Lymphocytic Leukaemia involves assessing the presence or absence of B symptoms of leukaemia as well as a peripheral blood smear assessment. At the end of three years a re-biopsy of the prostate revealed the presence of a residual malignant lymphomoid infiltrate (Figure 3).

 

Figure3: Core biopsy specimen showing lymphocytes staining strongly for CD 20 (left) and H&E staining showing monotonous lymphocytic infiltration of the core biopsy specimen of prostate (right).

 

A rescan showed the persistence of the pelvic mass but without increase in size and without any accompanying symptomatic haematuria or obstructive features.

 

Discussion
Infiltration of prostate by Chronic Lymphocytic Leukaemia is not an uncommon finding in patients with CLL. Autopsy studies have revealed CLL as the commonest secondary tumour of the prostate. Leukemic infiltration is symptomatic in only 1% of them (2). They usually present with outflow obstructive features. Chronic lymphocytic leukaemia has an indolent course with waxing and waning of the white cell count. As a haemopoietic malignancy involving the prostate, it cannot be cured by local therapies, though this has been claimed on short term follow-up in literature (3,4,5).
The prostatic component of the disease is best dealt with by radiotherapy if local problems are anticipated. Chemotherapy is reserved for patients who have systemic disease progression. Outflow obstruction is best relieved by Trans-urethral resection of the prostate. Though various doses have been cited for curative treatment of this disease, this claim is to be disputed. We currently recommend a dose of 24 Gray in 12 fractions for palliative control of symptoms as per the recommendation for a low-grade non Hodgkin’s lymphoma.
Urological follow-up of these patients is as that of other patients with outflow symptoms, who generally get a flow rate and rectal examination assessment. In addition they need to have continuous follow-up at a haematology clinic for monitoring their systemic symptoms, which may dictate the need for further intervention.
 

Lesson learnt:
• Leukaemic infiltration is not uncommon.
• It usually presents as bladder outflow obstruction requiring TURP.
• Radiotherapy is indicated only if local complications are anticipated and is not always curative.

 

References
1) https://www.rcr.ac.uk/docs/oncology/pdf/DoseFract_49_Lymphoma.pdf
2) E. H. Eddes et al, Urinary symptoms due to leukemic infiltration of the prostate A case report, Ann Haematol 1993, 66:323 – 324.
3) Mitch Jr et al, Leukemic infiltration of the prostate: A reversible form of urinary obstruction, Cancer 1970, 26: 1361-1365.
4) Belis JA, Lizza EF, Kim JC, Raich PC, Acute leukemic infiltration of the prostate. Successful treatment with radiation, Cancer 1983, 51: 2164–2167.
5) Belhiba H et al, Prostatic involvement in leukemia. Report of a case Progrès en Urologie 1992, Aug-Sep;2(4):650-2.

 

Date added to bjui.org: 15/12/2010


DOI: 10.1002/BJUIw-2010-063-web

 

© 2019 BJU International. All Rights Reserved.