Preventive Urology

8/3/2019 Preventive Urology

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Preventive UrologyPreventive Urology

Why talk about it?


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Preventive UrologyPreventive UrologyWhy talk about it?


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Preventive UrologyPreventive Urology Do we have substantial areas?

Stone disease

UTI Cancer Prostate

Prostatitis

Erectile dysfunction

Analyze role of Pharmaco-manipulationONLY. The Chemoprevention


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Stone Prevention StrategiesStone Prevention Strategies

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Preventing StonesPreventing Stones

Stone

Obesity

Diabetes

Diet

Fluids

K

Citrate

Juices

Drinks

Thiazides

Allopurinol

Na Bicarb

Drugs


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Stone Preventing PillsStone Preventing Pills K Citrate

Thiazides

Magnesium

Pyridoxine

K Citrate Thiazides

Magnesium

Pyridoxine

Obesity Gouty DiathesisDiabetes

AllopurinolNa Bicarb

STONA 1

STONA 2


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Oxalobacter FormigenesOxalobacter Formigenes

First strain isolatedfrom sheep rumen

Beneficial intestinalbacteria present in allvertebratesEnzymatically breaksdown oxalate to getenergy for its survival


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IxOC-4 TherapeuticIxOC-4 Therapeutic

Purified recombinant oxalatedegrading enzyme (OxalateDecarboxylase)

Formulated to degrade oxalate in thestomach

Indication: prevention ofenteric/absorptive hyperoxaluria andrecurrin calcium oxalate kidne stones


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Cancer Prostate PreventionStrategiesCancer Prostate PreventionStrategies

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Will controlling prostatic inflammationbe helpful in cancer prostate?Will controlling prostatic inflammationbe helpful in cancer prostate?


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COX-2COX-2 COX-2 enzyme over expression has been

reported in human prostate cancer

Cohen, et al 2007: COX-2 expression anindependent predictor of disease progressionin multivariate analysis in a sample of 60patients

COX-2 has role in proliferation, angiogenesisand also resistance to apoptosis


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COX-2COX-2 expression of the enzyme is correlated with

tumor progression

Liu et al, 2000: mice inoculated with humanprostate cancer cells produced tumors ofreduced size when treated with NSAID

Liu et al, 2002: PG E2 production(upregulation of COX-2) was found to inducePIN; could also stimulate this behavior usingIL-6


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NSAID & risk of prostate cancerNSAID & risk of prostate cancer Harris et al, 2005: reviewed 91 epidemiologic

studies & found a significant exponentialdecrease in cancer risk with heavier NSAIDregimens for7 out of10 cancer type


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NSAID and risk of prostate cancerNSAID and risk of prostate cancer Mahmud et al, meta-analysis of studies

published before 2003: use of aspirin reducedthe odds of prostate cancer


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NSAID & prostate cancer outcomesNSAID & prostate cancer outcomes There is reduced likelihood of highly

aggressive disease (Gleason score 8)forNSAID users

Selective COX-2 inhibition was able tosuppress the rate of PSA after curativetreatment


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Prostatitis Prevention strategiesProstatitis Prevention strategies

AllopurinolAlpha

BlockersFinasteride

Dutasteride

1980 2010


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UTI Prevention strategies in femalesUTI Prevention strategies in females

Antibioticprophylaxis

VaginalProbiotic

gels

CranberryJuice

B-Mannose ?

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The Need in the era of potent antibioticsThe Need in the era of potent antibiotics

The Extent:

Lifetime incidence of UTI : in every 5 women

Of these women, 3% experience recurrent disease

11 million women receive medication for UTI annually

Significant health problem worldwide

Why antibiotics alone may not be enough

Antibiotic resistance Side effects

Economic aspects


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Alternative, preventive and economic options to antibioticsare urgently needed


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Bacterial Adherence: essential step in theinitiation of UTI.

E-coli expresses 100-400 fimbria(pili) on itssurface by which it attaches itself to epithelialsurface of urinary tract and vagina.

Types: 1( Mannose sensitive, Most common)

P ( Mannose Resistant, Pyelonephritic)

S ( Sialic acid)

Others

Role of E-coli in UTIRole of E-coli in UTI


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BACTERIAL ADHERENCEBACTERIAL ADHERENCE


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Electron Microscopy view of E coliElectron Microscopy view of E coli


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Decrease bacterial adherence/wash them off


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CranberryCranberry

Cranberry (Vacciniummacrocarpon) is a fruit native toNorth America.

Massachusetts and Wisconsin:

main areas of present-daycommercial production ofcranberry.Major constituents of cranberry juice

glucose (3.1%),fructose (1%),citric acid (1.1%),quinic acid (1.1%),malic acid (0.8%).Cranberry juice cocktail is a 25% dilution of the native juice


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Clinical Evidence supporting cranberry use


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BMJ. 2001 Jun 30;322(7302):1571.

Randomised trial of cranberry-lingonberry juice and Lactobacillus GG drink for the prevention

of urinary tract infections in women.

A 20% reduction in absolute risk in the cranberry group compared with the control group (95%confidence interval 3% to 36%, P=0.023, number needed to treat=5, 95% confidence interval 3 to 34).

CONCLUSION: Regular drinking of cranberry juice but not lactobacillus seems to reduce therecurrence of urinary tract infection.

Can J Urol. 2002 Jun;9(3):1558-62.A randomized trial to evaluate effectiveness and cost effectiveness of naturopathic cranberry

products as prophylaxis against urinary tract infection in women.

RESULTS: Both cranberry juice and cranberry tablets statistically significantly decreased the numberof patients experiencing at least 1 symptomatic UTI/year (to 20% and 18% respectively) comparedwith placebo (to 32%) (p2symptomatic UTI's per year (assuming 3 days antibiotic coverage) and had >2 days of missed workor required protective undergarments for urgency incontinence. Total antibiotic consumption wasless annually in both treatment groups compared with placebo. Cost effectiveness ratiosdemonstrated cranberry tablets were twice as cost effective as organic juice for prevention.CONCLUSIONS: Cranberry tablets provided the most cost-effective prevention for UTI.


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DosageDosage

Recommended dosing for UTIprophylaxis

300-400mg BD (tablet of

concentrated cranberry extract)

8 oz of pure unsweetened

cranberryjuice TDS.

[About 700ml daily]


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Adverse effectsAdverse effects

No significant herb-drug reactions have been reported.

It may increase urinary oxalate levels.

Caution:Regular use of cranberry may increase the risk ofkidney stone formation in patients with a history ofoxalate calculi.


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D-MANNOSE is a sterioisomer of Glucose andnaturally present in fruits like pineapple andcranberry & also in plants and fungi.

Mannose binds to lectins ( glycoprotein onfimbriae of E-coli. ), preventing them fromcolonization .

D- MANNOSE IN UTID- MANNOSE IN UTI


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Absorbed from the upper GIT at a slower ratebut not stored as glycogen.

Most of it in blood stream is excreted in theurine unchanged.

Quality: possibility of dilution with other sugars.So analyzed by HPLC assay- ensure thatmannose content is > 99%.


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Available as capsules and in powder form.

Suggested Use: Three (3) capsules, two tothree times (2-3x) daily.

Powder: one spoon (3) times daily, mixed with

water, with or between meals.

Precaution: Diabetic (regular monitoring ofsugar levels is recommended).

FormulationsFormulations


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Probiotics


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Probiotics:Probiotics are defined as LIVE microorganisms which when

administered in adequate amounts confer a health benefit to the

host

Rationale:

The bacterial flora of the skin and mucosal surfaces is an

important barrier to infection and disruption of this natural flora

renders patients prone to infections which may be severe/

involving multiple organisms


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Mechanism of ActionMechanism of Action

Competitive Theory:

Probiotics administered orally/ applied togenital area overgrow pathogenic flora andrestore an environment resistant to infections

Compete for space/nutrition.

Produce metabolites which are bactericidal/bacteriostatic to pathogenic flora.

Non competitive Theory:

Immunomodulation

May influence the production of immunoglobulins thus altering the bodysimmune defense.

May contribute to a specific immune response against pathogenicbacteria


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Clinical Evidence supporting Probiotic use


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Can J Microbiol. 1988 Mar;34(3):339-43. Links

Intravaginal instillation of lactobacilli for prevention of recurrent urinary tract

infections.

Bruce AW, Reid G.

Department of Surgery, Toronto General Hospital, Ont., Canada.

Urinary tract infections remain a common problem, particularly in the femalepopulation. New methods are required to manage recurrent cystitis, and extensiveresearch to date has suggested that restoration of the lactobacilli flora of theurogenital tract may prevent these infections. In this study, five females sufferingfrom recurrent urinary tract infections were treated twice weekly with intravaginaland perineal implantation of Lactobacillus casei GR-1. These organisms colonizedthe epithelium and prevented the emergence of coliform bacteria in most instances,

but did not appear to affect enterococcal colonization. In vitro studies showed that L.casei GR-1 inhibited the growth of the coliforms but did not inhibit enterococci. Eachof the five patients had infection-free periods ranging from 4 weeks to 6months. The treatment was well tolerated, had no side effects, led to an improvedwell-being, and was preferred to antibiotic treatment by all of the patients. Thesehuman studies, albeit of a limited nature, are the first to examine the potential forlactobacillus therapy in the prevention of urinary tract infections. The results showthat lactobacilli therapy, using carefully selected organisms to treat patients who areclosely followed, may be effective in the prevention of recurrent urinary tractinfections.

Probiotic released from vaginal pessary


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Though there is insufficient data to

support routine use of probiotic in UTI, itmay be regarded as the single mostpowerful alternative option under

clinical development for the preventionand treatment of chronic infection


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Thank youThank you

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Preventive Urology