Urology and Men’s Health

17th June 2021 George Yardy Consultant Urological Surgeon The Ipswich Hospital, ESNEFT Topics covered

• Male LUTS – Case study – Medication – surgery

• Covid and urology

• Female incontinence and UTI – Case study – Catheters – Botox

• General paediatric urology – Foreskin – Groin

• Bladder pain syndrome / chronic prostatitis / chronic pelvic pain syndrome

• Vasectomy reversal

Male LUTS: case study Mr C.W., 72 y.o.

20/06/2017 Male LUTS / prostate assessment clinic

I yr urgency, frequency, nocturia x6, occ urge urinary incontinence No better with tamsulosin Satis. erectile fn.

PMH: hypertension, hernia repair DH: atorvastatin, losartan

RE: moderate (60g?) benign prostate

PSA 5.3, Creatinine 104, urine dip NAD Male LUTS: case study

• IPSS 20/35, QoL 5/6

• Frequency / volume chart: – Total 14 – 18 voids / 24h – Intake 4000ml / day Male LUTS: case study

• 19/07/2017 Urodynamics Male LUTS: case study

• 19/07/2017 Urodynamics Impression: Equivocal bladder outlet obstruction, no detrusor overactivity, empties fully. Ie. “sensory urge” Male LUTS: case study

• 07/08/2018 flexible cystoscopy – large occlusive prostate, bladder normal

• 12/02/2019 brought in for TURP but cancelled – c/o esp. urgency, some urge inco, not had med for this LUTS termiology

Lower urinary tract symptoms (LUTS) are storage, voiding and postmicturition symptoms affecting the lower urinary tract.

Bothersome LUTS may occur in up to 30% of men older than 65 years.

Storage Post Voiding (previously ‘irritative’) (previously ‘obstructive’) Micturition

weak or intermittent urgency urinary stream dribbling frequency straining incontinence hesitancy Nocturia terminal dribbling

incomplete emptying BPH and Progression Anatomy of BPH

NormalBPH

Bladder

Hypertrophied Prostate detrusor muscle

Urethra

Obstructed Adapted from Kirby RS et al. Benign Prostatic urinary flow Hyperplasia.Health Press 1999

Medication for LUTS • α blockers – Tamsulison, Alfuzosin – “uroselective” – Work quickly – days – s/e.s – dizzy (first doses?), ejaculatory dysfunction

• 5 α-reductase inhibitors – Finasteride, Dutasteride – Works only for larger prostates – Effect takes 3-6 months – s/e.s - libido, erections

• Combination α blocker / 5ARI – Decreases risk of progression (worsening IPSS, retention sugery) – If at risk (large prostate, PSA >1.4, IPSS >10

• PDE5 inhibitors – Some evidence of common pathophysiology of ED and LUTS – More relevant now generic Tadalafil available? Medication for LUTS

• Antimuscarinics – Low risk of retention if residual >200ml – Side effects – Generic Tolterodine, Solifenacin

• Β3 agonist – Mirabegron seems as effective as antimuscarinic, without side effects Male LUTS: case study

• Some improvement with tolterodine and physio • Repeat UDS 11/09/20

Definite bladder outlet obstruction, Minor detrusor overactivity

Listed for TURP Start finasteride to decrease intra-operative bleeding Surgical options

• “Cavitating procedures” – TURP – Laser operations

• “MIST” – minimally invasive surgical therapy – Urolift – prostatic urethral lift – Rezum – steam – PAE – prostate artery embolisation – iTIND – others on the way Conventional TURP

• Established “gold standard” – National Prostatectomy Audit BJUi 1995

• Monopolar diathermy – Affects pacemaker?

• Glycine irrigation – Resection time limited to 1 hour – Or else “TUR syndrome” – fluid overload, hyponatraemia, neurotoxic metabolites Bipolar TURP

• Mechanistically similar to TURP • Bipolar diathermy energy • Saline irrigation

• Allows longer resection • Better haemostasis / less blood loss • No TUR syndrome “TURis” – transurethral resection in saline

= Olympus PLASMA System

Introducing The UroLift® System Treatment

1. The UroLift delivery 2. UroLift implants are placed through a needle that 3. The UroLift delivery device is placed through comes out of the delivery device to lift the device is removed, the urethra to access enlarged prostate tissue out of the way. leaving a more open the enlarged prostate. urethra.

The UroLift ® System directly opens the urethra without prostate tissue removal or ablation.

20 The UroLift® System

• Single-use device • CE marked, TGA approved and now with a positive, finalized NICE guidance: – Indicated for the treatment of symptoms due to urinary outflow obstruction secondary to BPH in men over the age of 50.

Delivery device UroLift System

Implant

U.S. Patents: 7,645,286; 7,758,594; 7,766,923; 7,905,889; 8,007,503

21 UroLift® System Is A Whole New Approach

PRE POST

• Immediately opens the prostatic urethra • Can treat LUTS without compromising normal prostate function • Provides rapid relief without complications from prostate injury • Opens up a new option for urologists and patients

*Data on file at NeoTract, Inc.

22 •Day case •No catheter •Small / medium prostate •No ejaculatory dysfunction Prostate Aretry Embolisation

• Embolisation already established eg for refractory pelvic bleeding, fibroids

• Local anaesthesia, X-ray guidance • Groin approach -> femoral artery -> Super- selective catheterisation of small prostatic arteries • Embolisation with microparticles via fine microcatheters • Necrosis and shrinking of prostate

PAE

• Where does it fit in our BPH pathway?

• Complex but safe procedure • Men who wish to avoid or at least delay surgery but accept inferior symptom improvement and effect may be temporary

• Nigel Hacking, Interventional Radiologist, Southampton Rezum

• Steam / radiofrequency energy to ablate tissue • Prostate up to 80g • Transurethral • GA or sedation • Up to 20 minute procedure, day case • Catheter 4-7 days • No ED, little retrograde ejac

Summary of surgical options

• Cavitating procedures – Treat large prostates, severe symptoms – Significant improvement in sx, for long duration – low reoperation rate – Longer hospital stay and recovery

• MIST – Now accumulating experience nationally and locally – Short procedures, quicker recovery, lower sexual side effects – Do not improve sx as much, may require further procedure later Male LUTS: case study

•28/04/21 uneventful TURP 21g resected, histology benign

•clinic 09/06/21 Pleased Flow better Nocturia x3 (was x6) OAB symptoms likely to settle further over months

Covid

• effects of Covid on urinary tract • effects of Covid on urological services • prioritisation categories Effects of Covid on urinary tract

Bladder and kidney at risk of invasion ▪ SARS-CoV-2 spike protein binds to ACE2 receptors – detected on cells of kidney and bladder ▪ contribute to AKI in Covid +/- septic shock, cytokine storm, immune mech.s

Viral RNA • 6.9% Covid patients, remains positive after throat swab returns neg • but 0% in another study

No report of transmission to hospital staff via urine / bladder irrigation fluid Effect of Covid on urological services

Adapt, prioritise, delay, recover

Virtual clinics – great for some follow-ups, impossible for many new patients Referral delays England 2WW suspected urological cancer referral Feb 2020: 18,534 Apr 2020: 7,859 (58% reduction)

3/12 delay to diagnosis  10%  10 yr survival for bladder cancer little change for prostate / testis cancer

Risk prioritisation Theatre delays Nosocomial infection Operative prioritisation

• Priority 1a: <24h – Obstructed infected kidney – Uncontrolled haematuria – Fourniere gangrene

• Priority 1b: <72h – Upper urinary tract obstruction – Acute stones with pain / renal impairment – Penile # Operative prioritisation

• Priority 2: < 1/12 – Some MDT-directed bladder / renal cancer – Ureteroscopy for stones with stents – Visible haematuria investigation

• Priority 3: <3/12 – High / intermediate risk prostate cancer – Bladder outlet surgery in catheterised males – Non-visible haematuria investigation – Stent change – Orchidopexy for undescended testis Operative prioritisation

• Priority 4: >3/12 – Benign female incontinence – Uncomplicated stone surgery – ED, infertility – Low risk prostate cancer, superficial TCC – Bladder outlet surgery – TURP – Benign penoscrotal surgery

Case study: female with MS and urinary symptoms • Mrs MM. 55 yrs old • MS diagnosed 1989 – optic neuritis, right arm weakness

• 2007 weak left side of body, back pain, tingling & spasms both legs • 2008 short period in wheelchair

• Fluctuating, slowly progressive, unsteady walking • Received treatments inc Avonex, Copaxone, Tecfidera, pregabalin, baclofen

• Bladder overactivity initially controlled with oxybutinin Case study: female with MS and urinary symptoms: UTI • 2015 also recurrent UTI – Rx 6/12 continuous trimethoprim – Then “self-start” ABx

• 2016 Rx methenamine

• 2018 Cystistat Some general comments about recurrent UTI • USS worthwhile but cystoscopy rarely contributory in neurologically normal pre-menopausal female

• Men need flow rate +/- cystoscopy +/- Rx for chronic prostatitis

• Lifestyle advice: leaflet from RCGP / BAUS / patient.info

• Topical (intravaginal) oestrogen

• D-mannose (vs cranberry, lactobacillus) Some general comments about recurrent UTI • Antibiotics – Standby / self start – Trigger (eg. post-coital) – Continuous prophylactic • Resistance • Review at least 6 months • Not at all keen on “rotational” ABx

• Methenamine – “Hiprex” – Large tablet b.d., tastes of vinegar – Metabolised to formaldehyde in acidic urine – Surprisingly well-tolerated!

• Other (secondary care) – Instillations – Cystistat, Hyacyst Case study: female with MS and urinary symptoms: catheters • 2011 started intermittent self-catheterisation (ISC) – ISC frequently reqd in incomplete bladder emptying in MS – Rarely required after Botox in neurologically normal females

• 2016 constant bladder spasms and leakage, so suprapubic catheter (SPC) inserted Urinary catheters, Design and Usage

• Types of Catheter • Foley catheter – (including SPC) • Robinson – ISC catheters • 3 way • Coudé tip • Convene ‘catheter’ • Urodynamics catheters

• Catheter diameters are sized by the French catheter scale (F). The most common sizes are 10 F (3.3mm) to 28 F (9.3mm).

• Male and female lengths Urinary catheters

• Design: – Silicones. Good biocompatibility and biodurability due to low surface tension and hydrophobicity. Silicone catheters are thermally stable remaining essentially unaffected by repeated autoclaving. They can usually be dry-heat sterilized as well.

– polyvinyl chloride (PVC) – Now outdated.

– Latex rubber. from the sap of the Pará rubber tree. The use of latex gloves and condoms sharply increased in the 1980s. Increased reports of latex allergies, especially among healthcare workers. The prevalence of latex allergies among medical professionals has since been estimated to be between 8 and 17%. Urinary catheters • Design: – Foley catheters made entirely of silicone had less potential for bacterial migration compared to latex catheters with various coatings, including a silver- containing hydrogel. Sabbuba N et al. The migration of Proteus mirabilis and other urinary tract pathogens over Foley catheters. BJU International, 89:55-60, 2002.

– Silver-impregnated catheters have failed to demonstrate reduced catheter- associated bacteriuria, and also shown a significantly increased incidence of bacteriuria in male patients and a significantly increased occurrence of staphylococcal bacteriuria. Riley DK et al. A large randomized clinical trial of a silver-impregnated urinary catheter: lack of efficacy and staphylococcal superinfection. Am J Med. 1995 Apr;98(4):349-56.

– Gendine-coated urinary catheters: Bacteriuria was present in 60% uncoated catheters and 71% of those with silver hydrogel-coated catheters (P < 0.01) but not in those with Gendine-coated urinary catheters. Hachem R et al. Novel antiseptic urinary catheters for prevention of urinary tract infections: correlation of in vivo and in vitro test results. Antimicrob Agents Chemother. 2009 Dec;53(12):5145-9. Epub 2009 Oct 5.

– Other antibiotic-coated / bactericidal catheters in development Urinary catheters

ISC catheter

2 + 3 way urethral catheters Urinary catheters

• Uses: – Urine drainage • Long / short term due to BOO • Acute: urine output / haematuria • ISC

– Following urological surgery • RRP / cystectomy • Urethroplasty • TUR surgery

– Investigations • Cystourethrography • Urodynamics Urinary catheters

• Problems: – Infection rate is about 5% per day. – Escherichia coli remains the most common infecting organism – Bacteria tend to show increased resistance because of the repeated antimicrobial courses. – Urinary tract infection (UTI) usually follows formation of biofilm on both the internal and external catheter surface. The biofilm protects organisms from both antimicrobials and the host immune response. – Asymptomatic catheter-acquired UTI should not be treated with antimicrobials

– Other problems – Blockages, irritation, erosion of glans / meatus, trauma, bladder stones

– Long term = Possible Squamous Ca bladder Catheter Bypassing

• Exclude or treat recurrent blockages. • Limit balloon volume. • Anticholinergic medication. • Urethral surgery or closure. • Botox? blockage

• 40-50% of pt.s with LTC are frequent “blockers” • Encrustation – calcium phosphate, magnesium ammonium phosphate

• Biofilm inc Proteus generates alkaline urine – encourages crystal formation Catheter Blockages

• Mucinous debris or stones (30% of patients).

• Cystoscopy versus radiology.

• Increase catheter size.

• Change catheter brand and frequency of changes.

• Consider regular washouts – Acidic catheter maintenance solutions eg “Suby-G”

• Possible role for acidification (potassium citrate) and low-dose antibiotic prophylaxis. – But debris does not necessarily mean infection Catheters and Infection

• Urinary infection: Symptomatic and cloudy urine. Investigate upper tracts and bladder. Fluids and antibiotics. • Suprapubic infection: Local hygiene. Antibiotics. Miscellaneous Complications

• Bladder cancer – increased risk but unquantified. • Renal scarring – 50% of patients at post mortem. • Renal stones – 8% in 3 years with indwelling catheter (4% with ISC). • Psychological and sexual difficulties. • Effects on fertility. Case study: female with MS and urinary symptoms • Bladder Botox injections every 12-18 months since 2003 – London, then Cambridge, then IHT. • GA, then LA

• 2013 started using mirabegron as Botox wore off – prolonged interval between treatments • Effect of repeated treatments? Administration of Botulinum toxin • Flexible cystoscope • Instillagel • Into submucosa or detrusor, not beyond • 100-300 units BTX-A • 10-20 sites injected with 1-2ml each • Inject bladder base – Helpful for bladder pain – Effect lasts longer

IHT: 60 treatments / year usually outpatient, under LA ISC rarely reqd in neurologically normal females, almost always in males Lasts 9 – 18 months Reports of 7 repeat treatments equally effective Case study: female with MS and urinary symptoms • 09/2017 still recurrent UTI –  headache, poor vision, nausea, MS worse • Difficulties with SPC changes • Catheter spasm pain Case study: female with MS and urinary symptoms • 08/2018 ileal conduit urinary diversion – Operation uneventful – Fever day 5 – CT: pelvic collection – managed conservatively – Discharged on iv ABx

• 06/2020 OPC: “delighted” – No leak – No UTI – eGFR 93

Interstitial cystitis / bladder pain syndrome (BPS)

• Suprapubic pain related to bladder filling

• Increased daytime and night-time frequency

• Absence of infection or other pathology

Principal pathology:

• Infection? • Defective bladder epithelium / GAG layer? • Neurological? • Autoimmune?

BPS management

• Diet / lifestyle • Oral treatment • Intravesical therapy • Other Management

Diet Common substances that aggravate symptoms

•Alcohol •Citrus fruit •Fizzy drinks •Tomatoes •Caffeine •Spicy food Management

Oral therapy

• Amitriptyline •Anticonvulsants

• Analgesics •Immunosuppressive agents •Pentosan polysulfate sodium • Antihistamines

• Anti-inflammatory agents

• Anticholinergics Start with a course of antibiotics ? Management

Intravesical therapy

Chondroitin sulfate (Uracyst): substance that occurs naturally in the bladder GAG layer. Uracyst is a 2% concentration of chondroitin sulfate in a 20ml vial. This provides 400mg of chondroitin sulfate. Gepan is a 0.2% concentration in a 40ml vial. This provides 80mg of chondroitin sulfate

Sodium hyaluronate (Cystistat): not naturally present in the surface GAG layer of the bladder wall

Dimethyl sulfoxide (DMSO): appears to have anti-inflammatory, analgesic, and some muscle relaxant properties.

Heparin

BCG Management

Other therapies

Neuromodulation Usually S3 is targeted

Hydrodistension Techniques vary in time and volume of overdistension

Intradetrusor Botox

Surgical • Sympathectomy and intraspinal alcohol injections • Differential sacral neurotomy • Transurethral resection/laser of a Hunner's ulcer • Supratrigonal cystectomy • Urinary diversion with or without cystourethrectomy Conclusions

Women with BPS are an underdiagnosed and underserved group of patients

BPS is not a bladder disease – forms a chronic visceral pain syndrome

Management is challenging – often a trial and error approach is required

BPS: my approach

• Diet / lifestyle • (usually had Abx before see me) • Cystoscopy – looks inflamed or not? • Meds: antimuscarinic / amitriptyline / Quercetin / gabapentin • Intravesical Cystistat / Hyacyst / iAluRil • Botox Chronic prostatitis / chronic pelvic pain syndrome • Also highly prevalent • May or may not be post-infective Symptomatic NIH Classification

• Category I – Acute bacterial prostatitis – Acute onset of pain combined with irritative and obstructive voiding symptoms in a patient with systemic febrile illness – Urinary frequency, urgency, dysuria, perineal and suprapubic pain, obstructive symptoms and systemic symptoms

• Category II – Chronic bacterial prostatitis – History of documented UTI and chronic pelvic pain syndrome

• Category III Chronic pelvic pain syndrome – Symptoms no different between IIIA and B – Pain in perineum, suprapubic area, penis, lower back, groin, pain after ejaculation

• Category IV – Asymptomatic inflammatory prostatitis – Patients present with BPH, elevated PSA, infertility Chronic prostatitis / chronic pelvic pain syndrome • Pragmatic treatment pathway: • PSA and DRE not suspicious? • 3 As: – Antibiotics • At least 4/52 ciprofloxacin, ofloxacin, or trimethoprim – Alpha blockers – tamsulosin • Concomitant LUTS • Urine reflux into prostatic ducts?? – Anti-inflammatories • At least 2/52 regular NSAID Chronic prostatitis / chronic pelvic pain syndrome • Also – Quercetin: herbal. Bioflavaoid. Anti-inflammatory / antioxidant

• Then – Amitriptyline, nortriptyline, gabapentin

• Physio – “Pelvic headache” – Due to failure of relaxation of pelvic floor

• Pain clinic referral

Common paediatric conditions Foreskin Conditions

• Physiological vs pathological phimosis – Physiological: slightly red, “pouts” on attempted retraction – Pathological: thickened, scarred = BXO Light green = developmental unretractability of foreskin Red line = persistent preputial adhesions (no data pre 6yo) Indications for circumcision

• Pathological phimosis ie. BXO • Recurrent troublesome balano-posthitis • Otherwise not physiological phimosis unless persists beyond age 11 – 12 • Recurrent paraphimosis • Congenital abnormalities • Prevention of UTI with abnormal urinary tract

• NOT: – Ballooning, spraying Alternative to circumcison

• Topical steroid – Needs to be high potency – Betnovate or similar – Small amount to tight part of foreskin twice daily, followed by attempts at retraction – Uses steroid’s side effect – skin thinning – Up to 3 months – At best, 50% effective – Not licenced Summary

•  70% foreskins are retractile at 4 yrs • < 1% have non-retractile foreskin at 17 yrs • Medical Indications – Pathological phimosis (BXO) – Recurrent balanoposthitis – Recurrent UTI in abnormal renal tract • Complication rate 1-2%

• “The fortunate foreskin of an infant boy will usually be left well alone by everyone but its owner” Groin conditions

• Undescended testis • Hydrocoele • Hernia Normal Testicular Descent

Week 7 Gubernaculum appears

Week 23 Testis starts descent

Week 24 – 28 Testis traverses inguinal canal in 75%

28 weeks Descent complete in most (75%) Classification UDT

Incidence Definition

Retractile Common Cremaster causes testis to ride up into inguinal canal Needs no treatment but close observation

Ectopic <5% Testis migrates to abnormal location below ext ring (perineum, base penis, femoral area)

Incomplete 95% Testis arrested on normal path descent descent (abdominal, inguinal, pre-scrotal)

Absent Rare Classification Incidence UDT

• One of commonest congenital anomalies • At birth: – 3% unilateral UDT – bilateral UDT 20 times less common – 1% persist 1yr • More common if – Pre term – Low birth weight – Small for dates – Twin • InfertilityWhy Treat? – Risks of UDT • Neoplasia • Hernia • Torsion

• Psychological / aesthetic

When to operate? • V contentious • 12 months? • 6 months? Retractile testes

• Functionally normal

• Rarely require orchidopexy

• Usually become less retractile with time

• “Ascending testis” rare – age 10-12 – Or is it? Maybe most of orchidopexies performed after age 5 are ascending Hydrocoele vs hernia Hydrocoeles

• Unobliterated/patent processus vaginalis • Usually asymptomatic • Commonly bilateral • 90% spontaneously resolve • Repair if persists beyond infancy: after age 3 – Ligation of processus Herniae

• Indirect • Complete • 1-2% of births ( in prems) • Intermittent • Reducible lump in groin

•Early herniotomy (<2-3 weeks of diagnosis) Paed surgery summary

• Foreskin: – refer pathological phimosis – Physiological phimosis only if particularly symptomatic • Recurrent balanitis • Age > 11-12 • Not “ballooning”

• Undescended testes get operated on soon after 1st birthday

• Hydrocoele / PPV only after age 3 • Umbilical hernia only after age 4

Microsurgical vasectomy reversal Microsurgical vasectomy reversal

• 16% of men <70 in UK have had vasectomy • 6% subsequently choose reversal

• Advantages cf. ART: – Opportunity to conceive more naturally – Lower cost cf. IVF/ICSI cycle – Higher success rate Success rate influenced by:

• 1) time interval from vasectomy to reversal • 2) partner’s age and fertility history • 3) Technique

• Microsurgical 3 layer anastomosis • My audited figures: – overall, 75% have positive semen analysis – Longest interval 22 years!

• Emerging issues:

• There is a growing awareness that many urological conditions are associated with obesity, inactivity and metabolic syndrome, which highlights the need for holistic assessment and care of patients with urological problems Summary

• Male LUTS – update on medication, surgical options • Covid and Urology • Female bladder problems – OAB, UTI; catheters • Pelvic pain • Paediatric – try not to refer physiological phimosis • Vasectomy reversal – 75% positive semen analysis

Thank you [email protected]