Tag Archive for: BPH

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Article of the Month: The Metabolic Syndrome & the Prostate

Every Month, the Editor-in-Chief selects an Article of the Month 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.

Association between metabolic syndrome and intravesical prostatic protrusion in patients with benign prostatic enlargement and lower urinary tract symptoms (MIPS Study)

Giorgio I. Russo*, Federica Regis*, Pietro Spatafora, Jacopo Frizzi, Daniele Urzı*, Sebastiano Cimino*, Sergio Serni, Marco Carini, Mauro Gacci† and Giuseppe Morgia*

 

*Urology Section, Department of Surgery, University of Catania, Catania, Italy, and Department of Urology, University of Florence, Florence, Italy

 

Abstract

Objective

To investigate the association between metabolic syndrome (MetS) and morphological features of benign prostatic enlargement (BPE), including total prostate volume (TPV), transitional zone volume (TZV) and intravesical prostatic protrusion (IPP).

Patients and Methods

Between January 2015 and January 2017, 224 consecutive men aged >50 years presenting with lower urinary tract symptoms (LUTS) suggestive of BPE were recruited to this multicentre cross‐sectional study. MetS was defined according to International Diabetes Federation criteria. Multivariate linear and logistic regression models were performed to verify factors associated with IPP, TZV and TPV.

Results

Patients with MetS were observed to have a significant increase in IPP (P < 0.01), TPV (P < 0.01) and TZV (P = 0.02). On linear regression analysis, adjusted for age and metabolic factors of MetS, we found that high‐density lipoprotein (HDL) cholesterol was negatively associated with IPP (r = −0.17), TPV (r = −0.19) and TZV (r = −0.17), while hypertension was positively associated with IPP (r = 0.16), TPV (r = 0.19) and TZV (r = 0.16). On multivariate logistic regression analysis adjusted for age and factors of MetS, hypertension (categorical; odds ratio [OR] 2.95), HDL cholesterol (OR 0.94) and triglycerides (OR 1.01) were independent predictors of TPV ≥ 40 mL. We also found that HDL cholesterol (OR 0.86), hypertension (OR 2.0) and waist circumference (OR 1.09) were significantly associated with TZV ≥ 20 mL. On age‐adjusted logistic regression analysis, MetS was significantly associated with IPP ≥ 10 mm (OR 34.0; P < 0.01), TZV ≥ 20 mL (OR 4.40; P < 0.01) and TPV ≥ 40 mL (OR 5.89; P = 0.03).

Conclusion

We found an association between MetS and BPE, demonstrating a relationship with IPP.

Infographic: Impact of dutasteride/tamsulosin combination therapy on sexual function in men with LUTS secondary to BPH

Infographic: Impact of dutasteride/tamsulosin combination therapy on sexual function in men with LUTS secondary to BPH

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Article of the Week: Impact of dutasteride/tamsulosin combination therapy on sexual function in men with LUTS secondary to BPH

Every Week, the Editor-in-Chief selects an 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 month, it should be this one.

A prospective randomised placebo‐controlled study of the impact of dutasteride/tamsulosin combination therapy on sexual function domains in sexually active men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH)

 

Claus G. Roehrborn*, Michael J. Manyak, Juan Manuel Palacios-MorenoTimothy H. Wilson§, Erik P.M. Roos, Javier Cambronero Santos**, Dimitrios Karanastasis††Janet Plastino‡‡, Francois Giuliano§§ and Raymond C. Rosen¶¶

 

*Department of Urology, University of Texas (UT) Southwestern Medical Center, Dallas, TX, USA, GlaxoSmithKline (GSK), Washington, DC, USA, GSK, Madrid, Spain, §PAREXEL International, Durham, NC, USA, Antonius Ziekenhuis Sneek, Sneek, The Netherlands, **Hospital Universitario Infanta Leonor, Madrid, Spain, ††Urologic Clinic, General Hospital of Athens Elpis, Athens, Greece, ‡‡GSK, Collegeville, PA,USA, §§Neuro-Urology R. Poincare Hospital AP-HP, Garches, UMR1179 Inserm-UVSQ-Paris Saclay University, Paris, France, France, and ¶¶New England Research Institutes,nWatertown, MA, USA

 

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Abstract

Objective

To prospectively assess the impact of the fixed‐dose combination (FDC) of the 5α‐reductase inhibitor (5ARI), dutasteride 0.5 mg and the α1‐adrenoceptor antagonist, tamsulosin 0.4 mg (DUT‐TAM FDC) therapy on sexual function domain scores in sexually active men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH), using the Men’s Sexual Health Questionnaire (MSHQ).

Patients and Methods

This European and Australian double‐blind, placebo‐controlled, parallel‐group study was conducted at 51 centres. Inclusion criteria: age ≥50 years, International Prostate Symptom Score ≥12, prostate volume ≥30 cc, prostate‐specific antigen 1.5–10 ng/mL. Patients were randomised 1:1 to DUT‐TAM FDC therapy or placebo for 12 months. The change from baseline to Month 12 on the total MSHQ (primary endpoint) and MSHQ erection, ejaculation and satisfaction domains (secondary outcome) was assessed, using a mixed model repeated measures analysis. Safety was evaluated.

Results

The intention‐to‐treat population included 489 patients (243 DUT‐TAM FDC therapy; 246 placebo). A significant decrease (worsening) was observed with DUT‐TAM FDC therapy versus placebo on the total MSHQ score (−8.7 vs −0.7; standard error [se]: 0.81, 0.78; P < 0.001), and the ejaculation (−7.5 vs −0.6; se: 0.56, 0.55; P < 0.001) and satisfaction (−0.6 vs +0.3; se: 0.3, 0.29, P = 0.047) domains, but not the erection domain (−1.0 vs −0.5; se: 0.19, 0.19, P = 0.091).

Conclusion

This is the first domain‐specific quantitative evaluation of DUT‐TAM FDC therapy on sexual function in men with LUTS secondary to BPH. The observed changes in the MSHQ with DUT‐TAM FDC therapy were mainly driven by changes in the ejaculation domain. These findings will help give context to erectile and ejaculatory dysfunction AEs reported spontaneously in earlier 5ARI studies.

Royal Society of Medicine: Key issues in Endourology

The RSM section of Urology #RSMUrology hosted a day on the Key issues in Endourology on 20th October. This was the first meeting of the academic year under President Roland Morley. Sri Sriprisad put together a complete endourology day with key subject areas of  “PCNL and stones”, “upper tract TCC” and “BPH and retention”. Speakers from India, America and Spain provided expert opinions from around the globe.

The day started with the evolution of stone and urological laparoscopic surgery. Showing an insight into the challenges with the initial introduction of laparoscopic urological surgery. In order to allow surgeons the chance to discuss their experiences and troubleshoot and develop surgical techniques the SLUG forum (southern laparoscopic urology group) was created, which is still running today in the annual AUA meeting.

PCNL techniques were the subject for several debate lectures. Access for PCNL tracts was debated by Dr Janak Desai, visiting from Samved Urology hospital in India, arguing for fluoroscopic puncture with over 10,000 cases to date! Jonathan Glass, from Guy’s and St. Thomas’ Hospital, spoke for the prone position for the majority of PCNL, but selecting the supine position in 5-10% of cases depending on the anatomy and stone position. Dr Desai also spoke on ultra-mini PCNL, which he advocates using to treat solitary kidney stones under 2 cm in preference to flexible ureteroscopy.

The future of ESWL was debated and the audience voted that it is still “alive and clicking” by a narrow margin. However, although up to 80% clearance rates are quoted for upper pole stones less than 2 cm, the problem is that results of treatment are varied and unpredictable, and real-life success rates are far inferior. The variation in results may in part be due to the fact that there are no formal training courses for specialist radiographers nor SAC requirements for specialist registrars. Professor Sam McClinton presented on clinical research in stone disease with results from the TISU trial on primary ESWL vs. ureteroscopy for ureteric stones due out next year. The results will be fascinating and may help to decide if ESWL has a future in the UK.

Professor Margaret Pearle, visiting from the University of Texas Southwestern Medical Centre, explained the importance of treating residual fragments. With data showing that 20 – 36% of >2 mm residual stones after ureteroscopy required repeat surgery within 1 year. In a thought provoking lecture, she presented data showing that ureteroscopy may not be as good as we think and when critically examined, true stone-free rates maybe no better than ESWL. Maybe miniaturised PCNL is the way forward after all?

The follow up of small kidney stones is an uncertain area with very little written in either the EAU or AUA guidelines. Data from a meta-analysis by Ghani et al. shows that for every year of follow up on small kidney stones 7% may pass, 14% grow and 7% will require intervention. However, it is not possible in most health systems to follow everyone up forever and Mr Bultitude advocated increasing discharge rates from stone clinics to primary care after an agreed time of stability, allowing more on the complex and metabolic stone formers.Figure 1- Stone follow up algorithm

The expert stone panel then debated several challenging cases including “the encrusted stent”, stones in a pelvic kidney or calyceal diverticulum. These cases certainly are a challenge and require an individualized approach usually with multi-modality treatments.

Figure 2 – Stone expert panel

Upper tract urological biopsies are notoriously inaccurate, with only 15% of standard biopsies quantifiable histologically. Low grade tumours, are potentially suitable for endoscopic management with laser ablation. Dr Alberto Breda, from the urology department of Fundacio Puigvert Hospital in Spain, presented a novel solution for the future. This promising new technology uses confocal endomicroscopy to grade upper tract urological cancer. Initial results show 90% accuracy in diagnosing low grade tumours, which could then be safely managed endoscopically avoiding nephron-ureterectomy for some patients.

 

Figure 3 – Confocal endomicroscopy for upper tract malignancy

In the final session, a debate on BPH treatment, the audience preferred the bipolar resection technique for treating “the 60 year old with retention, with a 90 gram prostate and on rivaroxaban”, although HOLEP came a close second, with that talk giving the quote of the day “I spend more time with the morcellator than the wife.”

Figure 4 – Bipolar TURP wins the day

 

Nishant Bedi

ST4 Specialist urology registrar

 

Article of the Week: Prostatic urethral lift vs transurethral resection of the prostate

Every week the Editor-in-Chief selects an 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.

Prostatic urethral lift vs transurethral resection of the prostate: 2-year results of the BPH6 prospective, multicentre, randomized study

Christian Gratzke*, Neil Barber, Mark J. Speakman, Richard Berges§Ulrich Wetterauer, Damien Greene**, Karl-Dietrich Sievert††, Christopher R. Chapple‡‡Jacob M. Patterson‡‡, Lasse Fahrenkrug§§, Martin Schoenthaler¶ and Jens Sonksen

 

§§*Department of Urology, Ludwig-Maximilians University, Munich, Germany, † Frimley Park Hospital NHS Foundation Trust, Surrey, UK, Department of Urology, Taunton and Somerset NHS Trust, Taunton, UK, §PAN Klinik Koln, Koln, Germany, Department of Urology, University Hospital Freiburg, Freiburg, Germany, **City Hospitals Sunderland, Sunderland, UK, ††University Clinic of Lubeck, Lubeck, Germany, ‡‡Shefeld Teaching Hospitals NHS Foundation Trust, Shefeld, UK, and §§Department of Urology, Herlev Hospital, Herlev, Denmark

 

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Abstract

Objectives

To compare prostatic urethral lift (PUL) with transurethral resection of the prostate (TURP) with regard to symptoms, recovery experience, sexual function, continence, safety, quality of life, sleep and overall patient perception.

Patients and Methods

A total of 80 patients with lower urinary tract symptoms attributable to benign prostatic hyperplasia (BPH) were enrolled in a prospective, randomized, controlled, non-blinded study conducted at 10 European centres. The BPH6 responder endpoint assessed symptom relief, quality of recovery, erectile function preservation, ejaculatory function preservation, continence preservation and safety. Additional evaluations of patient perspective, quality of life and sleep were prospectively collected, analysed and presented for the first time.

aotw-may-3-results

Results

Significant improvements in International Prostate Symptom Score (IPSS), IPSS quality of life (QoL), BPH Impact Index (BPHII), and maximum urinary flow rate (Qmax) were observed in both arms throughout the 2-year follow up. Change in IPSS and Qmax in the TURP arm were superior to the PUL arm. Improvements in IPSS QoL and BPHII score were not statistically different between the study arms. PUL resulted in superior quality of recovery, ejaculatory function preservation and performance on the composite BPH6 index. Ejaculatory function bother scores did not change significantly in either treatment arm. TURP significantly compromised continence function at 2 weeks and 3 months. Only PUL resulted in statistically significant improvement in sleep.

Conclusion

PUL was compared to TURP in a randomised, controlled study which further characterized both modalities so that care providers and patients can better understand the net benefit when selecting a treatment option.

Editorial: The BPH6 study raises the bar on how we should conduct BPH surgical trials

We have all done it. We’ve all shaken our heads with bemusement when men have severe symptoms, as would be defined by the IPSS, yet their response to the quality-of-life question would either be ‘delighted’ or ‘satisfied’. Likewise, we may see men who have objective multiple-fold improvement in their urinary flow rates after a BPH surgical procedure but are more unhappy about their urinary function than they were with their preoperative state. Such mismatches in clinician and patient expectation are not uncommon in clinical practice and are likely, in part, to be a reflection of what measurements clinicians and patients consider to be of importance.

The BPH6 study has challenged the traditional way in which the success of a surgical treatment has been assessed [1]. When prostatic urethral lift (PUL) was compared with TURP in the setting of a randomized controlled trial, there was clearly superior performance of the former as highlighted by a patient-centred outcome metric referred to as the BPH6. It could be argued on the one hand that the combined metric games the outcome in favour of PUL, given that known shortfalls in TURP outcomes, such as recovery, sexual dysfunction and morbidity, could not see it fairly compete with a minimally invasive surgical treatment, but, on the other hand, perhaps the BPH6 metric is just measuring what matters to our patients. The BPH6 is made up of variables that are not in any way new and have all either been established or validated ways of measuring outcomes. A valid criticism, however, is that the combined BPH6 metric is yet to be validated.

Gratze et al. [2] report the 2-year results of the BPH6 study, in a paper that is a great deal more than just a progress report. It represents the most comprehensive patient-centred outcome and quality-of-life assessment ever performed on BPH surgical procedures. Their study also introduces several patient-centred outcome measures that were not reported in the 1-year publication. Additional to the now already well-described BPH6 variables, the study includes the Patient Global Impression of Improvement (PGI-I), the Short-Form Health Survey (SF-12) with its derivative SF-6D utility score, the minimal clinical important difference (MCID) and the Jenkins Sleep Questionnaire.

The PGI-I is perhaps the true test as to what a patient thinks about the effectiveness of a surgical procedure. There is no ambiguity about a response to a direct question as to whether a patient perceives a treatment to have improved or worsened their condition. Whilst the origins of the PGI-I are in the non-urological literature, it has recently been making its way into BPH clinical studies [3, 4]. This should be encouraged and we should indeed dare to ask our patients whether they consider our treatment has lead to improvement or otherwise.

The MCID has been used extensively in the medical literature since its introduction in 1989 [5]. The BPH6 study is the first clinical trial on BPH surgical treatment to use this metric. The MCID is exactly as the term is defined, and is assessed across a range of measures in the paper by Gratze et al. in the context of quality of life. A literature search will reveal that urologists have been very late to the party, but this study will probably have a role-modelling effect with regard to the future use of the MCID in health-related quality of life assessments in BPH studies.

The BPH6 study raises the bar for how we should measure the full impact of the surgical treatment of BPH. There has never been a clinical study that has explored patient-centred outcome measures and quality of life after surgical treatment of BPH to an extent that is even remotely close to that reported here. Whether the combined BPH6 metric becomes popularized or not is less important than the fact that future clinical trials will undoubtedly see an adoption of patient-measured outcomes. Such measures could play an increasingly important role in the decision process for health funders to support a new or existing treatment as well as assist patients in understanding the trade-off between the negative and positive impacts of treatment. We can expect to see plenty of future work that will attempt to verify these assertions.

Read the full article

How to Cite

Woo, H. H. (2017), The BPH6 study raises the bar on how we should conduct BPH surgical trials. BJU International, 119: 654–655. doi: 10.1111/bju.13815

Henry H. Woo
Sydney Adventist Hospital Clinical School, University of Sydney, Sydney, NSW, Australia

 

References

 

 

RSM Urology Winter Meeting 2017, Northstar, California

rsm-2017-blogThis year’s Annual RSM Urology Section Winter Meeting, hosted by Roger Kirby and Matt Bultitude, was held in Lake Tahoe, California.

A pre-conference trip to sunny Los Angeles provided a warm-up to the meeting for a group of delegates who flew out early to visit Professor Indy Gill at the Keck School of Medicine.  We were treated to a diverse range of live open, endourological and robotic surgery; highlights included a salvage RARP with extended lymph node dissection and a robotic simple prostatectomy which was presented as an alternative option for units with a robot but no/limited HoLEP expertise.

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On arrival to Northstar, Dr Stacy Loeb (NYU) officially opened the meeting by reviewing the social media urology highlights from 2016. Next up was Professor Joseph Smith (Nashville) who gave us a fascinating insight into the last 100 years of urology as seen through the Journal of Urology. Much like today, prostate cancer and BPH were areas of significant interest although, in contrast, early papers focused heavily on venereal disease, TB and the development of cystoscopy. Perhaps most interesting was a slightly hair-raising description of the management of IVC bleeding from 1927; the operating surgeon was advised to clamp as much tissue as possible, close and then return to theatre a week later in the hopes the bleeding had ceased!

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With the promise of beautifully groomed pistes and stunning views of Lake Tahoe, it was hardly surprising that the meeting was attended by a record number of trainees. One of the highlights of the trainee session was the hilarious balloon debate which saw participants trying to convince the audience of how best to manage BPH in the newly inaugurated President Trump. Although strong arguments were put forward for finasteride, sildenafil, Urolift, PVP and HoLEP, TURP ultimately won the debate. A disclaimer: this was a fictional scenario and, to the best of my knowledge, Donald Trump does not have BPH.

The meeting also provided updates on prostate, renal and bladder cancer. A standout highlight was Professor Nick James’ presentation on STAMPEDE which summarized the trial’s key results and gave us a taste of the upcoming data we can expect to see in the next few years.

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We were fortunate to be joined by prominent American faculty including Dr Trinity Bivalacqua (Johns Hopkins) and Dr Matt Cooperberg (UCSF) who provided state-of-the-art lectures on potential therapeutic targets and biomarkers in bladder and prostate cancer which promise to usher in a new era of personalized therapy.

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A personal highlight was Tuesday’s session on learning from complications. It was great to hear some very senior and experienced surgeons speaking candidly about their worst complications. As a trainee, it served as a reminder that complications are inevitable in surgery and that it is not their absence which distinguishes a good surgeon but rather the ability to manage them well.

There was also plenty for those interested in benign disease, including topical discussions on how to best provide care to an increasingly ageing population with multiple co-morbidities. This was followed by some lively point-counterpoint sessions on robot-assisted versus open renal transplantation (Ravi Barod and Tim O’Brien), Urolift vs TURP (Tom McNicholas and Matt Bultitude) and HOLEP vs prostate artery embolization for BPH (Ben Challacombe and Rick Popert). Professor Culley Carson (University of North Carolina) concluded the session with a state-of-the art lecture on testosterone replacement.

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In addition to the excellent academic programme, delegates enjoyed fantastic skiing with perfect weather and unparalleled views of the Sierra Nevada Mountains. For the more adventurous skiiers, there was also a trip to Squaw Valley, the home of the 1960 Winter Olympics. Another highlight was a Western-themed dinner on the shores of Lake Tahoe which culminated in almost all delegates trying their hand at line dancing to varying degrees of success! I have no doubt that next year’s meeting in Corvara, Italy will be equally successful and would especially encourage trainees to attend what promises to be another excellent week of skiing and urological education.

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Miss Niyati Lobo
ST3 Urology Trainee, Brighton and Sussex University Hospitals NHS Trust

@niyatilobo

 

Tagore’s Last Days: the little Prostate ends a big Legend

tagoreKabiguru Rabindranath Tagore is perpetually present in the Bengali memory and is a part and parcel of the Indian cultural fabric even after 75 years of his demise. The Bard of Bengal has retained his greatness through his songs, poetry, stories, progressive world view and love for his country.

The first Nobel Prize winner of Asia (1913), Tagore was knighted in 1915 and had the courage to return it as a mark of protest after the Jalianawala Bagh massacre in 1919. He is compared to the likes of William Shakespeare and Johann Wolfgang Goethe for his extraordinarily rich literature and sensitive understanding of human nature.

Rabindranath has been a hero, an idol and a father figure for the Bengali. That is why when it comes to his death there is a self-imposed oblivion among his followers because there is an aversion to accept that he too was human, he too had suffered in his last days.

The way the city cried and the huge congregation of people that came to pay him their last respects go on to show the place Tagore had in the heart of the Kolkatan. But very few people actually know that Kabiguru Rabindranath Tagore did not allow his deteriorating health to affect his spirit.

Seventy-five years after his death this is the first time Tagore’s illness has been revealed and his last days talked about. At an exhibition organised at Tagore’s home ‘Jorsanko Thakur Bari’ on his death anniversary on August 7, 2016 with the official approval of the Rabindra Bharati University Museum, the verandah of his home came alive with photographs and exposition of his last days when Tagore smiled through extreme pain and was surrounded by family and friends. The exhibition showed that despite his failing health he remained positive and at his creative best, and how doctors did their best to make him feel better. Rabindra Bharati University, that is housed in the premises of Tagore’s home, and Kolkata Prostate Cancer Foundation led by the author of this blog, organized this exhibition. It is evident that Tagore died from the complications of an enlarged prostate gland.

Tagore was a handsome man blessed with a good physique and an impressive personality. For the sake of building his body, he even learnt how to wrestle and lived a disciplined life. He learnt horse riding and had commendable stamina, which enabled him to swim across the Padma River. Despite this his health deteriorated at the age of 76 and unfortunately on 10th September, 1937 he lost consciousness and remained that way for two days. Kidney and prostate problems were diagnosed simultaneously. His health demanded immediate attention, which was duly given to him in Shantiniketan by a team of doctors headed by Dr Nilratan Sarkar from Kolkata.

He was also suffering from ailments like fever, headache, chest pains and a lack of appetite. Tagore strongly believed that his life had a meaning beyond these mortal diseases. That’s why the moment he could sit upright on his bed he took to his ink and paper. His love for nature was not only restricted to the stories he wrote, indeed he profoundly believed that he would feel much better if he spent his time in the lap of nature.  That is why he kept visiting the hills of North-Eastern India.

He also ensured that his creativity did not suffer. Even in such trying times he wrote ‘Sejuti’, ‘Naba Jatak’ and ‘Shyama’. He also composed numerous songs and painted to his heart’s content. Tagore cared deeply for his country and despite his ill health he continued to have political discussions with Jawaharlal Nehru and Subhash Chandra Bose. He played host to Mahatma Gandhi and his wife Kasturba when they visited Shantiniketan. It seemed that his deteriorating health was the least of his worries.

On 15th September, 1940 when Tagore was in Kalimpong, due to a pain in his urinary bladder he lost consciousness again. He was unable to pass urine either. Despite the evident symptoms of uraemia, his grand-daughter, Pratima Debi wasn’t ready to accept that Tagore needed an operation. On 29th September, he was brought back to his Jorasanko House on the advice of Dr Prasanto Chandra Mohalanobis.

With the help of Dr Satyasabha Mitra, Dr Amiya Basu and Dr Mahalanobis he was moved to the marble room on the first floor where he spent most of his time. In the presence of his near and dear ones along with dutiful attendants and under the supervision of Sir Nilratan Sarkar and Dr Bidhan Chandra Roy he seemed to be on the path of recovery.

A considerable amount of attention was given to his diet, medicines and cleanliness in order to ensure complete recovery. The poet continued to have his biochemic medicines, which he felt would also give him relief. Dr Dakhshinaranjan Roy visited him regularly and advised him.

On his return to Shantiniketan it seemed, Tagore had come to terms with his failing health and was determined to win this battle without dampening his spirits. He narrated a sea of stories every now and then and his imagination took on the colour of his palette. What emerged were timeless paintings. Around this time he also welcomed the Chinese missionary Tai-Chi-Tao with open arms.

It was the Poush Utsav in December that year, actually the last one that Tagore witnessed, when it dawned on him that time plays the most crucial role in one’s life. The harder he tried to hold on to time, it slipped away from him. Despite the mental and physical struggle, he managed to stand by his beliefs and played an active part in some major protests demanding independence for India. His works ‘Golpo Solpo’ and ‘Teen Sangee’ reflected these precise thoughts in his last days.

Despite this positivity his illness persisted. Because of the constant persuasion of doctors, both, allopathic and ayurvedic treatments were started in a desperate attempt to revive him. On 16th July, 1941, his doctors advised him to undergo surgery.

The operation was scheduled for 30th July. But he was not informed about it for fear that he would not accept it. On the day of the operation after making all arrangements, Dr Lalit Bandopadhyay finally broke the news to Tagore that he would be operated upon. The poet was shocked and not very happy; however, he was taken to the verandah of his house where a special operation theatre had been created for him. A Suprapubic Cystotomy was performed where the doctors aimed to insert a tube into his bladder to relieve his urinary retention. The operation was done by Dr Lalit Bandopadhyay, assisted by Dr Satysakha Maitra and Dr Amiya Sen.

After the operation, he often complained of a burning sensation but thankfully remained unconscious most of the time. To everyone’s dismay, his condition worsened and his pain was evident even while he was unconscious. On 4th August his kidneys stopped working and uremia had set in. Saline was administered to him and oxygen was kept handy. On the night of 6th August, his condition had hit rock bottom and people started gathering in the premises of Jorasanko.

Slowly oxygen tubes were removed and Tagore’s spirit freed itself from the shackles of a human body, at 12.10 pm. The news spread like wildfire and thousands of people rushed to Jorasanko to pay their last respects. The deafening silence of the crowd was broken by the blowing of conch shells. Flowers carpeted his path to the crematorium on the banks of the Ganges.

The echo of his words from “The Postmaster” keep coming to my mind. He said: “So, the traveller, borne on the breast of the swift-flowing river, consoled himself with philosophical reflections on the numerous meetings and partings going on in the world – on death, the great parting, from which none returns.”

A line from his famous song sums up his last days:

Exists Sorrows, Exists Death, Separation Chars,

Yet Exists Peace, Yet Exists Happiness, Yet The Infinite Stirs.

 

Dr. Amit Ghose, Kolkata, India

 

IN THE MEDIA:

“Finally, when his condition worsened and he had almost stopped passing urine, doctors diagnosed him with severe uremia and other complications. It was then decided that surgery could not be postponed any further and the poet was brought back to Jorasanko. It was here that a sterilized OT was created for the surgery conducted by Lalit Bandyopadhyay and overseen by BC Roy and Nil Ratan Sircar. They did not operate on the enlarged prostrate, but did a bypass surgery to take out accumulated urine. The prostate had to be left untouched,” said urologist Amit Ghose, who has been supervising the installation of the exhibition – Published in the Times Of India, August 7, 2016

“Not many people know that Kabiguru Rabindranath Tagore suffered from a disease of the Prostate Gland (not cancer). At that time he was given the best medical treatment possible. With the advancement of technology in India we are well-equipped to detect and handle diseases related to the prostate. Also, we wanted to create an awareness through this initiative that with regular check-ups it is possible to have an early detection of prostate-related issues and prostate cancer as well,” said the person behind this initiative, Dr. Amit Ghose, Director, Prostrate Cancer Foundation. – Published in BusinessWire India, August 9, 2016

The kind of love and care Rabindranath Tagore had got from everyone around him also is something to talk about. The doctors treating him tried their level best and they often sat by his bedside holding his hand hoping the pain and the discomfort would subside,” said Dr Ghose. – Published in Asia Times, August 21, 2016

 

 

Article of the Week: eNOS G894T gene polymorphism and responsiveness to a selective α1-blocker in BPH/LUTS

Every Week the Editor-in-Chief selects an 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.

The association of endothelial nitric oxide synthase (eNOS) G894T gene polymorphism with responsiveness to a selective α1-blocker in men with benign prostatic hyperplasia related lower urinary tract symptoms

Yung-Chin Lee*,, Yung-Shun Juan*,,, Chia-Chu Liu*,,§, Bo-Ying Bao,**,††, Chii-Jye
Wang*,, Wen-Jeng Wu*,, Chun-Nung Huang*,† and Shu-Pin Huang*,,‡‡
*Department of Urology, Department of Urology, Faculty of Medicine, Kaohsiung Medical University, Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, §Department of Health, Executive Yuan, Pingtung Hospital, Pingtung,

 

Department of Pharmacy, **Sex Hormone Research Center, China Medical University Hospital, ††Department of Nursing, Asia University, Taichung, and ‡‡Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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Objective

To prospectively investigate the association of endothelial nitric oxide synthase (eNOS) G894T gene polymorphism with responsiveness to a selective α1-blocker in men with benign prostatic hyperplasia related lower urinary tract symptoms (BPH/LUTS), as nitric oxide has recently gained increasing recognition as an important neurotransmitter of functions in the lower urinary tract.

Patients and Methods

In all, 136 men with BPH/LUTS were recruited from urology outpatient clinics in a university hospital. Oral therapy with doxazosin gastrointestinal therapeutic system (GITS) 4 mg once-daily was given for 12 weeks. The drug efficacy was assessed by the changes from baseline in the total International Prostate Symptom Score (IPSS), maximum urinary flow rate (Qmax) and post-void residual urine volume (PVR) at 12 weeks of treatment. The ‘responders’ to doxazosin GITS were defined as those who had a total IPSS decrease of >4 points from baseline. eNOS G894T polymorphism was determined using the polymerase chain reaction-restriction fragment length polymorphism method.

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Results

Patients had statistically significant improvements in total IPSS, quality of life score, and Qmax (P < 0.01) after a 12-week period of treatment. Using multiple logistic regression analysis adjusted for age and IPSS, our results showed that being a eNOS 894T allele carrier was an independent risk factor for being a drug non-responder (P = 0.03, odds ratio 4.19). Moreover, a decreased responder rate (P = 0.01), as well as the lower improvements in IPSS (P = 0.02) and Qmax (P = 0.03) were significantly associated with increment in the T allele number.

Conclusions

The presence of the eNOS 894T allele had a significantly negative impact on responsiveness to a selective α1-blocker in BPH/LUTS treatment, suggesting that eNOS G894T gene polymorphism may be a genetic susceptibility factor for α1-blocker efficacy in men with BPH/LUTS.

Editorial: Responsiveness to Medical BPH Therapy – Is There a Genetic Factor?

In this issue, Lee et al. [1] from Taiwan demonstrate that the endothelial nitric oxide synthase (eNOS) G894T gene polymorphism predicts responsiveness to α1-blocker therapy in men with BPH/LUTS.

There is a long-standing interest in the establishment of a genetic marker for BPH/LUTS predicting clinical status, the natural history and – ideally – also responsiveness to for example medical therapy. The high prevalence of disease, the socioeconomic impact of diagnosis, medical and surgical treatment, and the availability of drugs (5α-reductase inhibitors) that alter the natural course of the disease justify the intensive search for a genetic marker for BPH/LUTS.

The few familial and twin studies suggest a (moderate) genetic background for this disease to an extent similar to other chronic diseases such as hypertension or diabetes mellitus type II [2, 3]. However, BPH/LUTS is a complex disorder and it is very unlikely that the pathogenesis can be reduced to a single gene or gene defect. Most likely, genetic alterations – besides inflammation, endocrine, myogenic, neurogenic, and morphological factors – act as co-factors.

Within the past decade numerous polymorphisms in the steroid-metabolism pathway, in cytokine genes, in the vitamin D receptor gene, the α-adrenoceptor gene, in homeobox genes, in the angiotensin converting enzyme, the glutathione S-transferase gene, and in the nitric oxide system (just to mention the most frequently studied ones) have been correlated to several clinical parameters of BPH/LUTS, such as symptom status, prostate volume, maximum urinary flow rate and the natural history of the disease [4, 5]. None of these studies provided compelling evidence that one of these polymorphisms (or combinations thereof) could serve as a clinically relevant marker [4, 5]. As indicated by Cartwright et al. [5], many of these genetic studies are hampered by a small sample size, lack of genotyping quality control, inadequate adjustment for populations from heterogeneous descent groups, and poorly defined/inhomogeneous study endpoints.

There is increasing evidence that the nitric oxide (NO)/cGMP pathway plays an important role in controlling the smooth muscle tone of the lower urinary tract. Decreases in the NO/cGMP pathway with age would result in decreased levels of intracellular cGMP and calcium, leading to less smooth muscle relaxation of the bladder and the prostate, thus worsening LUTS. NO is synthesised by at least three isoenzymes of NOS, inducible NOS (iNOS), neuronal NOS (nNOS) and eNOS [1]. The close relationship between NOS/NO pathway and the pathophysiology of BPH/LUTS was the rationale for the study by Lee et al. [1]. Using multiple logistic regression analysis adjusted for age and IPSS, the data showed that the eNOS 894T allele carrier was an independent factor for drug non-responders [1]. However, responsiveness to α1-blocker therapy was also strongly dependent on diabetes mellitus and hypertension, suggesting that the metabolic syndrome plays an important role in the pathogenesis of BPH/LUTS [1]. This is indeed the first study showing that a genetic factor is predictive of the responsiveness to medical BPH/LUTS therapy, therefore this study is significant.

Further studies in populations with other genetic backgrounds (e.g. Caucasian) are required to confirm and to generalise these data. Phosphodiesterase type 5 inhibitors have been proposed to act in BPH/LUTS via the NO systems; therefore, it would be interesting to test this genetic marker also in men treated with tadalafil 5 mg/day. Finally, one has to be aware of the fact that the authors have tested α-blocker monotherapy. All major guidelines recommend a combination of α-blocker and 5α-reductase inhibitor for men with larger prostates (e.g. prostate volume >30–40 mL) [6]. The mean prostate volume in this cohort was 35 mL suggesting that, according to guideline recommendations, these men would have required combined therapy [6].

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Stephan Madersbacher, Professor and Chairman
Department of Urology, Kaiser-Franz-Josef Spital, Vienna, Austria

 

References

 

 

2 Partin AW, Page WF, Lee BR, Sanda MG, Miller RN, Walsh PCConcordance rates for benign prostatic disease among twins suggest hereditary inuence. Urology 1994; 44: 64650

 

3 Rohrmann S, Fallin MD, Page WF et al. Concordance rates and modiable risk factors for lower urinary tract symptoms in twins. Epidemiology 2006; 17: 41927

 

4 Konwar R, Chattopadhyay N, Bid HK. Genetic polymorphism and pathogenesis of benign prostatic hyperplasia. BJU Int 2008; 102: 53643

 

 

6 Gravas S, Bach T, Bachmann A et al. Treatment of Non-Neurogenic Male LUTS. Available at: www.uroweb.org. Accessed March 2016.

 

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