Managing the Male Patient

From the Albany Medical College and the Urological Institute of Northeastern New York’s symposium on
Current Concepts in Men’s Health

Educational Objectives

The goal of this program is to improve evidence-based treatment of Peyronie’s disease (PD) and of urologic compli­cations in male patients with spinal cord (SC) injuries. After hearing and assimilating this program, the clinician will be better able to:

1.   Discuss fibrotic and antifibrotic molecular etiologies of PD.

2.   Assess evidence base for oral, injection, and surgical treatments for PD.

3.   Choose candidates for surgery and apply individual treatments to correct penile curvature.

4.   Explain treatment strategies for patients with SC injury and flaccid or spastic bladders.

5.   Devise plans for acute and long-term treatment and follow-up in patients with SC injury.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any per­sonal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes qual­ity in health care and not a proprietary business or commercial interest. For this program, Drs. White and Pranikoff and the planning committee reported nothing to disclose.

Acknowledgments

Drs. White and Pranikoff were recorded at Current Concepts in Men’s Health 2008, sponsored by Albany Medical College and the Urological Institute of Northeastern New York, and held August 8-10, 2008, in Bolton Landing, New York. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

Peyronie’s Disease

Mark D. White, MD, Associate Professor of Surgery, Albany Medical College, Albany, NY

Molecular etiologies in Peyronie’s disease (PD)

Fibrotic changes: transforming growth factor-1 (TGF-1)  —activates collagen synthesis, but disordered collagen laid down; released by neutrophils and macrophages; central modulator of collagen deposition; fibrin and plasmino­gen activators and inhibitors involved; plasmin breaks down extracellular matrix; matrix metalloproteinases (MMPs) also involved; excess fibrin can induce PD plaques

Antifibrotic changes : more well-studied; MMP enzymes; breakdown of type I collagen  —  involves MMP 1 and 13; breakdown of type III collagen – involves MMP 1, 3, 10, and 13; nitric oxide synthase (NOS) pathway probably involved; genetic predispositions (eg, Dupuytren’s contractures)

Treatment (American Urology Association [AUA] 2008 survey): 46 questions on practice patterns; 639 AUA members responded; majority general urologists; »66% treat <10 PD patients per month; treatment  —  >50% use observation for PD of <1 yr duration (38% use observation as main treatment); medical management  —  72% use oral agents; 5% use transdermal agent (eg, verapamil), injection  therapy (»8%), and shock wave therapy (1%; pro­motes more scarring); oral therapies  —vitamin E (64%); vitamin B derivative (9%; aminobenzoate potassium [Po­taba]); colchicine (10%); transdermal therapy  —  verapamil (27%); injection therapies  —  include verapamil, steroids, and interferon; surgical therapy  —  majority perform plication; followed by plaque incision and grafting, and implant surgery; wait before surgery  —majority wait £ 1 yr after PD onset and after plaque stabilization; grafting  —  many use autologous vein grafts; implants  —  most use 3-piece inflatable devices

Clinical presentation: penile lump or curvature; concerns about erectile dysfunction (ED) or painful erections; record  — plaque size, location, and degree of curvature; degree of ED; duration of disease; pain perception (pain scores)

Diagnostic testing: ultrasonography (US)  —  some utility for assessing corporal calcification and fibrosis; contrast in­jections and cavernosography  —  rarely needed; photographs  —  anteroposterior and lateral views

Patient counseling: variable disease timeline and progression; involve partner; surgical intervention  —  avoid during acute inflammatory phase; plaque remodeling phase  —  plaque stabilizes and shrinks (in certain cases with injection therapy); spontaneous resolution rate »13% (not commonly seen)

Evidence for Common Oral Therapies

Vitamin E: antioxidant; may shorten inflammatory phase of disease; not effective in trials for reducing curvature; may be helpful for pain; 400 IU considered safe (higher doses may increase lung cancer risk); conclusion  —  some pain relief but no other evidence of benefit

Colchicine: targets microtubule formation; early studies show decreased pain, plaque size, and curvature; no long-term studies; used once daily or every other day (3-6 mo) to stabilize plaque; side effect

Aminobenzoate potassium: difficult to tolerate (24-40 500-mg tablets daily; »$300/mo); vitamin B complex; de­creases serotonin; may decrease fibrogenesis; severe gastrointestinal side effects; studies  —  slight decrease in plaque size; no change in curvature

Tamoxifen: nonsteroidal antiandrogen; blocks TGF receptors; may slow fibrosis; alopecia side effect; no improve­ment shown in trials

Promising agents: 1) carnitine  —   may inhibit acetyl coenzyme-A; may repair damaged cells; may improve plaques; smaller studies show slight improvement in pain and curvature; inexpensive ($15/mo); needs additional study; 2) L-arginine  —NOS pathway; possibly antifibrotic; may reduce plaque size; not well studied in humans; inexpensive; 3) pentoxifylline (eg, Trental)  —  nonspecific phosphodiesterase (PDE) inhibitor; increases cyclic adenosine mono­phosphate; reduces Type I collagen synthesis; studies show decrease in plaque size and altered collagen/fibroblast ratio; low side-effect profile; »$25/ month; patient compliance challenging

Topical verapamil: trials designed poorly; expensive ($200-$300/mo); unable to achieve therapeutic concentration in tunica albuginea; treatment  —  can soften plaque, and reduce curvature and pain (some patients note improved erection quality); stability achieved at »1 yr

Injectable Therapies

Steroids: best study shows 3% improvement after 1 yr; decreased pain and plaque size; side effects  —  local tissue at­rophy, fibrosis, and immune suppression

Collagenases: for small plaque size and curvature (30˚-60˚), modest improvement; clinical trials under way; concern  —  source is Clostridium cultures

Verapamil: inhibits local extracellular matrix proliferation by fibroblasts (increases local collagenase); demonstrated size decreases in plaques; improvements in curvature and pain; regimen  —  every 1 to 2 wk (with local anesthetic); after 6 to 12 injections, re-evaluate; contraindicated  —  ventral plaques or extensive plaque calcifications; some studies show double concentration may cut treatment time; concern  —  studies small

Interferon alfa: increases collagenase; decreases fibroblast proliferation; costly ($5000-$7000 per cycle); 67% im­provement in pain; improvement in curvature; small studies; feasible for patients who fail other therapies

Parathyroid hormone: thought to decrease collagen synthesis; some subjective decrease in curvature; no follow-up studies

Other Approaches

Iontophoresis: verapamil and dexamethasone combinations may increase drug penetration and wound healing; slight improvement in curvature shown

Penile traction devices: improvement in curvature; improved flaccid stretched penile length and hinge effect; no re­currence or worsening of curvature (short follow-up in studies); $400; motivated patient

Multimodal approach: pentoxifylline tid; L-arginine (1000 mg po bid); traction device for 6 mo; verapamil injec­tions (when stable phase achieved) to improve curvature and reduce pain; if ineffective, re-evaluate and discuss sur­gical options

Shock wave therapy: studies show no change in curvature, plaque size, sexual function, or rigidity; may worsen plaque formation (local tissue trauma); evidence lacking

Surgical Therapies and Outcomes

When to use: failure of medical therapy; chronic phase of disease; excessive deformity (ED with, eg, hourglass de­formity or ventral curvature)

Nesbit/Yachia plications: 9 studies (1-359 patients); relatively safe; discuss changes in glans sensitivity; follow-up for 1 yr to 89 mo  —  satisfaction rates (60%-100%); penile straightening (73%-100%), penile shortening (0%-100%); sensory changes (3%-24%); postoperative (PO) ED (»10%)

Other plications: 21 to 124 patients followed £4 yr; high satisfaction; penile straightening (29%-91%); penile short­ening common; sensory changes (4.5%-50%); higher degree of postoperative ED (6%-40%)

Grafts: autologous  —  6 to 50 patients followed <4 yr; satisfaction variable; improved straightening; penile shorten­ing; PO ED higher (3.7%-100%); saphenous vein  —  moderate contraction occurs; 8 studies (8-113 patients fol­lowed »5 yr); straightening; some shortening; higher PO ED rates; additional plication sutures needed for straightening; cadaveric tissues  —6 studies (<100 patients each); longer follow-up; straightening; pitfalls include shortening, PO ED, and sensory changes

Penile prosthesis : 12 studies (20-145 patients); high satisfaction rates; many require additional procedures to straighten

Treatment algorithm: stable disease  —  6 to 12 mo without curvature change; pain free; if <60˚ curvature with ade­quate length (PDE-5-responsive or no ED)  —  plication (reduction in PO ED, best for ventral bend or distal curva­ture); discuss penile shortening and palpable sutures; >60˚ with shorter penile length (PDE-5-responsive or no ED)  —  grafting procedure can correct complex deformities; best for proximal curvature; higher risk for PO ED (10%-25%); many have glans paresthesia and sensory changes; if >60˚ curvature and shorter penile length  —  fix problem (no PO ED, no recurrence of deformity, and no need for postoperative PDE-5 inhibitors); pitfalls include risk for infection, and high cost

Urologic Management of the Patient with Spinal Cord Injury

Kevin Pranikoff, MD, Associate Professor of Urology and Rehabilitation Medicine, State University of New York at Buffalo, School of Medicine and Biomedical Sciences, and Clinical Director of Urology, Erie County Medical Center, Buffalo, NY

Spinal cord (SC) injury: review (Nakajima 1989)  —  urinary tract infection major cause of death; indwelling catheters  —compared to intermittent catheterization, complication rates higher; lower motor neuron lesion  —  if around sacral cord, flaccid bladder; if lesion higher, spastic bladder in »80% of patients

Treatment goals: preserve kidneys  —  first priority; prevent high-pressure storage, infections, stones, and retention; continence  —  managing urine flow; varying clinical approaches (according to sex and extent of injury); intermittent catheterization  —  prevents bladder overdistention

Flaccid bladder: intermittent catheterization  —  ideal; dependent on hand function; facilitated in some individuals by abdominal stoma; hemi-Indiana pouch  —  place high on abdomen for visualization; other options  —  incontinence stoma or long-term catheterization (patients with poor hand function or poor motivation); Credé or Valsalva maneuvers  —  rarely appropriate (studies show harmful); suitable for sacral injuries and pudendal nerve involve­ment (low outlet resistance)

Spastic bladder in paraplegics: intermittent catheterization or reflex voiding (discuss options with patient); inter­mittent catheterization  —  suppress spasms using anticholinergic agent (high doses, in combination therapy); if anti­cholinergics fail  —botulinum toxin type A or bladder augmentation;  sphincterotomy; condom catheters in men; in women, abdominal stoma or Foley catheter; bethanechol  —  only parasympathomimetic drug; no large trials; works in some patients; alpha blockers  —decrease outlet resistance in men and women

Spastic bladders in quadriplegic patients: good hand function  —consider options for paraplegic; poor hand function  —  indwelling catheter or pad for women; condom catheter; abdominal stoma (high stoma easier for care­giver)

Follow-up Steps

Acute postinjury: urethral preservation  —  iatrogenic injury often occurs from indwelling catheter in patients with long stays in intensive care unit (ICU) (damage sometimes irreparable); speaker advocates placement of suprapubic catheter early on to preserve urethra

Intermediate term (first year): incomplete lesions changing; mental adaptation by patient; avoid irreversible ma­neuvers (use suprapubic catheters to preserve urethra); occasional sphincterotomy for intractable autonomic dysre­flexia (AD)

Long term (³1 yr): preserve urinary tract; patients require lifelong follow-up (can suddenly develop high-pressure bladder or AD); follow with upper tract study; yearly US (renal scan more sensitive in patients with hydronephro­sis); US may miss amyloidosis or early changes without hydronephrosis; urodynamics  —  yearly (less often if pa­tient stable 5 yr); cystography  —  in selected patients (if vesicoureteral reflux suspected); reflux  —  discuss alternatives; cystoscopy  — patients with bladder stones; increased incidence of transitional cell and squamous cell tumors

Urodynamics: recreate symptoms (especially AD), eg, patients will show lower-extremity spasms related to bladder or other abdominal sensations; high-pressure bladder  —  common concern if patient shows rise in volume, detrusor sphincter dyssynergia (DSD), uninhibited contraction, and increase in electromyographic activity during contrac­tion

Treatment of ED: affects quality of life (eg, depression, loss in self-esteem); PDE-5 inhibitors  —  best choice (ran­domized trials support use); vacuum devices  —  exaggerated lumbar lordosis makes use difficult; patients unrespon­sive to PDE-5 inhibitors  —  injection therapy or penile prosthesis; higher rates of complications, infections, and erosions (choose candidates carefully)

Ejaculatory failure: penile vibratory stimulation  —  recommend patients try on their own; successful (except in pa­tients with T10 area lesions); semen quality better than that using electroejaculation; in patients with high cord le­sions (T7 and above), watch for AD; electroejaculation  —  success »75%; may fail in T10 to T12 lesions; may be painful for patients with incomplete injury; if patient prone to AD, perform in controlled environment (eg, ICU); factors include variable semen quality, eg, decreased motility; patients with indwelling catheters  often have poorer semen quality and less success; cumbersome; expensive

Catheters: avoid if possible; concerns  —  stones and urethral destruction, irritation, incontinence, increased bladder spasticity, hematuria, encrustations and blockage, and bacteriuria; use smallest catheter possible for shortest time; silicon  —  optimal for short term; better tolerated by urethra and most tissues in body; for future use of urethra  —  consider suprapubic catheters; keep all catheters loose and fixed high to thigh or abdomen to prevent erosion; encrustation  —  timeline determined on individual basis (based on previous catheter); treating blockage  —  try saline first, then citric acid derivative (eg, Renacidin) (can be painful)

Bacteriuria: all patients with catheters; do not treat if asymptomatic; look for fever; avoid treating odor and cloudi­ness alone; if no indwelling catheter (and if symptomatic)  —  sterilize urine at least once; treat based on culture; spasticity and abdominal sensations  —  document; obtain urine sample via catheter; treat with specific antibiotics (document when symptom clears); choose antibiotics carefully; nitrofurantoin  —  antimicrobial concentrated in uri­nary tract; not for treating systemic symptoms (eg, fever, malaise); useful for cystitis

AD overview: common with injury at T6 and higher; »66% to 100% of patients manifest some symptoms; common response to distention of pelvic viscera; can be life-threatening

Signs and symptoms: paroxysmal hypertension; vasoconstriction below lesion; vasodilation, piloerection, and sweating above lesion; headaches, bradycardia, and blurred vision (or temporary blindness)

Acute treatment: eliminate cause; prevent bladder distention; if in urodynamics laboratory, stop testing and empty bladder; check for bowel distention; may relate to infected decubitus or other stimulus (eg, ingrown toenail); sit patient up (decreases headache); sublingual