This document discusses chronic prostatitis and its potential relationship to prostate cancer. It suggests that long-term chronic inflammation can potentially lead to prostate cancer through several mechanisms, including the production of growth factors and mutagenic compounds. It also describes a pre-cancerous lesion called Proliferative Inflammatory Atrophy (PIA) that has been observed adjacent to prostate cancer tumors. Several studies have found an association between past prostatitis and increased prostate cancer risk. Effective treatment of chronic bacterial prostatitis may help reduce this risk.

1. ADVANCEMENT IN PROSTATE CANCER
CHRONIC PROSTATITIS AND CaP:
ACTUALITY AND CLINICAL IMPLICATION
Giancarlo Comeri
Multimedica – Castellanza (Va)

2. CHRONIC INFECTION AND CANCER
• Some virus induce cancers by acting directly on target
cells:
• Human papillomaviruses
• Epstein-Barr virus
• For most of the infectious agents, included those of STIs,
the disease appears by an indirect mechanism:
• Long-standing chronic inflammation leads to
prolonged exposure of tissues to cancer-causing
agents produced in response to infection or toxins

3. CHRONIC INFLAMMATION AND CANCER
• Inflammation may contribute to carcinogenesis by several
potential mechanisms, including:
1. Elaboration of cytokines and growth factors that
favor tumor cell growth (TNF-alfa, VEGF, etc)
2. Induction of cyclooxygenase-2 (COX-2) in
macrophages and epithelial cells
3. Generation of mutagenic reactive oxygen species
(ROS) and reactive nitrogen species (RNS)
• The processes are interrelated

4. PROLIFERATIVE INFLAMMATORY ATROPHY
(PIA)
• Described by Angelo De Marzo in 1999 (Am J Pathol )
• Focal atrophic lesions containing activated inflammatory
cells and proliferating epithelial cells are often directly
adjacent to HGPIN, PCa or to both
• Somatic genomic abnormalities are similar to those in
cells with HGPIN and PCa

5. NEJM 349: 366, 2003

6. Meta-analysis of 11 case-control studies revealed a statistically significant
summary OR of prostate cancer of 1.57 for ever having had prostatitis.
Urology
2002;60:78-83
A recent medical records review vs age-matched controls confirms this risk:
Any type of prostatitis: OR 1.7 Acute prostatitis: OR 2.5
Chronic bacterial prostatitis: OR 1.6 Chronic pelvic pain syndrome: OR 0.9
(Robert et Al. Epidemiology, 2004)
Infections may represent one mechanism through which prostate cancer
develops. However, casuality is unclear, because recall bias and detection

8. HISTOPATHOLOGIC CLASSIFICATION SYSTEM
FOR CHRONIC PROSTATIC INFLAMMATION
• Anatomic localisation
glandular
periglandular
stromal
• Extension
focal
multifocal
diffuse
• Grading
1
2
3
Nickel et Al. BJU Int., 2001

9. CHRONIC BACTERIAL PROSTATITIS
–The most important cause of recurrent UTI in
adult man
–Frequently asymptomatic between an UTI
episode and the next one
–5-10% of the patients with CP/CPPS have a
CBP
Krieger JN 1998 J New Rem Clin 47:4-15;
Schaeffer AJ 1999 IJAA 11: 205-211

12. ISOLATED BACTERIA FROM CBP IN
RECENT CLINICAL TRIALS
(USA and EUROPE)
Trial Ciproflox. Lomeflox 400mg od Trovaflox. 200mg Levoflox. 500 mg od
500 mg bid vs od vs
28 days Ciproflox 500mg bid Vs Ciproflox 500 mg bid.
28 days Ofloxac.300 mg bid 28 days
42 days
Isolated 70 190 395 406
bacteria
Gram + 16 (23%) 76 (40%) 322 (81.5%) 344 (85%)
Gram - 54 (77 %) 114 (60 %) 73 (18.5%) 62 (15%)
Study 1990-1992 1993-1996 1995-1996 2000-2001
Period
References Naber & al., Naber & al., 2002 FDA web site Bundrick(2003)
2000

13. FLUORQUINOLONS ARE THE CHOISE DRUGS
FOR TREATMENT OF CHRONIC BACTERIAL
PROSTATITIS
• Good activity vs Gram + and Gram – usually isolated
in CBP
• Favourable pharmacocynetic proprieties and elevated
diffusion into prostatic tissue
• Clinical and microbiological efficacy widely tested
• Long time period treatment (not less than 4-6 weeks)
• Best results with NSAIDs’ association

14. EFFICACY OF QUINOLONES IN PCB TREATMENT
Quinolone Dosage Duration evaluable Bacteriol. Follow Pub.-year
per day therapy Patients Eradication up
Author(s)
( mg) (days) (number) (%) (Months)
Norfloxacin 800 28 14 64 6 1990
Schaeffer et al
Norfloxacin 4-800 174 42 60 8 1991
Petrikkos et al
Ofloxacin 400 14 21 67 12 1989 Pust
et al
Ciprofloxacin 1000 14 15 60 12 1987
Weidner et al
Ciprofloxacin 1000 28 16 63 21-36 1991
Weidner et al
Ciprofloxacin 1000 28 34 76 6 2000
Naber et al
Ciprofloxacin vs. 1000 28 78 72 6 2001
Naber et al Lomefloxacin 400 28 75 63 6 2001
Diagnosis according Meares & Stamey
Nickel, Naber & Lobel, WHO Consultation, Paris 2005

15. LVX 500 mg od vs CIP 500 mg bid for 28 days
(Bundrick et al., Urology,2003)
Primary endpoint Levofloxacina Ciprofloxacina [IC]
(5-18 days >EOT)
Eradication 102/106 96/125 [-8.98;12.58]
in PPb population (75 %) (76.8%)
(Primary efficacy
variable)
Clinical success 102/136 91/125 [-13.27;8.87]
In PPb population (75%) (73%)

16. CATECHIN : SINERGY EFFECT TO
QUINOLONES
• Catechin, an extract of green tea, has
antimicrobial effect against various bacteria and
synergy effect to antibiotics
• Combination treatment of catechin and
ciprofloxacin showed a statistically significant
decrease in bacterial growth and improvements
in prostate inflammation compared with
ciprofloxacin group (p<0.05) in an experimental
CBP models induced in Wistar rats.
( Lee et Al, Int J Urol, 2005)

17. ROLE OF CHLAMYDIA T. AND
UREAPLASMA U. IN CBP
• Only one systematic review (Weidner et al 2002)
• The simple checking of U. urealyticum and/or C.
trachomatis with the 4-glass test is not sufficient to
consider these organisms as aetiological agents of CP/
CPPS
• The microbiological techniques now available cannot
diversify urethral contamination from prostatic
infection
Anderson & Weidner, WHO Consultation, Paris 2005

18. CHOISE DRUGS FOR CHLAMYDIA T.
Comparative analysis of azithromycin and ciprofloxacin in the
treatment of chronic prostatitis caused by Chlamydia
trachomatis. (Skerk et All. Int J Antimicrob Agents. 2003)
Azytromicin 3 day therapy of 1x500 mg weekly for 3 weeks vs Ciprofloxacin 500 mg
b.i.d. for 20 days
Significantly higher eradication (36/45 vs 17/44; p=0.0002) and significantly higer
clinical cure (31/45 vs 15/44; p=0,0021) were achieved in the group of patients
treated with AZITHROMICINE than in the ciprofloxacin group.
Comparative randomized pilot study of azythromicin and doxycycline
efficacy in the treatment of prostate infection caused by
Chlamydia trachomatis ((Skerk et All. Int J Antimicrob Agents. 2004)
Azythromicin 1x1000mg (single dose) weekly for 4 weeks vs Doxycycline 100 mg b.i.d.
for 28 days
There was no significant difference between the eradication rates (A 65/82; D 33/43;
p= 0.82) and the clinical cure rate (A 56/82, D 30/43 p= 0.94) of the two
antimicrobials

20. HISTOPATHOLOGICAL STUDIES IN CP/CPPS
• Only few studies (4) on this subject have been conducted
• Infiltrates of chronic inflammatory cells were found from
33% to 88% of the cases
• Predominantly periglandular and stromal lymphocytes
• Many bias are related to the different biopsy’s techniques
and to the small number of cores
(Schmidt et Al., J Urol, 1966; Nielsen et Al, J Urol,1973; Doble et Al, Br. J Urol, 1989; True et Al. J
Urol ,1999)

21. CP/CPPS: BACTERIAL ETIOLOGY?
• Bacterial etiology may be invoked even if an organism is
not isolated but WBCs count is positive in EPS/VB3
• Nonspecific bacterial ribosomal RNA encoding (16S
rRNA) shows positive bacterial signals in EPS though
negative microbiological cultures in high % of cases
• Some studies with PCR prove bacterial implication in
prostatic patterns that are negative at microbiological
examinations
(Hochreiter et Al., J Urol. 2000; Tanner et Al. J Clin Microbiol,1999)

22. CP/CPPS : A CHALLENGE
• Dyssynergic voiding patterns?
• Inflammatory disregulation of the injury response
leading to persistent chemokine upregulation, oxidant
stress, and cellular damage ?
• Neurogenic inflammation?
(Kaplan et Al. J Urol, 1997)
( Satyanarayana & Shoskes, Mol Med Today, 1997)

23. URINARY TRACT INNERVATION
Detrusor contraction
Ach
Para-
sympathetic Ach Trigone and
M sphyncter
neurons
relaxation
Sympathetic Trigone contraction
neurons NA α1
Sphyncter contraction
Neurogenic Inflammation
Primary Symptoms perception (LUTS)
sensitive SP
neuron CGRP Irritation-Pain
TRPV1
Capsaicine
TRPV1: vanilloide receptor subtype1, tipical pain receptor, to which irritant substances as Capsaicine bind
oneself CGRP = calcitonine gene related peptide  mastcells activation  inflammation

24. NEUROGENIC INFLAMMATION AND CPPS
• The transient receptor potential vanilloid subtype 1
(TRPV1) is an ion channel activated by capsaicin that is
involved in pain’s perception and in bladder’s
contractions frequency
(Avelino and Cruz, Naunyn SchmeiedebergArch Pharmas 2006)
• Recent discovery in normal prostatic tissue of a rich
TRPV1 sensory innervation may open new therapeutical
perspectives for treatment of pain in CPPS
(Dinis et Al, Eur. Urol.,2005)
• The expression in urothelial and prostatic cancer cells of
TRPV1 raises the exciting hypothesis that this receptor is
also involved in cell differentiation
(Sanchez et Al, Eur J Pharmacol, 2005)

25. PRIMARY SENSITIVE NEURON
(NOCICEPTOR)
Bladder
Urethra
Prostate Irritative
stimula (capsaicin) Dorsal Marrow
SP SP c-fos
CGRP CGRP Irritation-
Neurogenic Glutammate/Aspartate pain
Inflammation
Irritation - Pain
The peripheric effect is the beginning of all inflammmatory phenomena’s fall
(oedema, parvicellular infiltration, cytokynes production etc.)
The central effect is the sending of painful informations to upper centers by the c-
fos  pain sensation  starting-signal of the efferent mechanisms as contractions
etc.

26. ALFA-1 ADRENOCEPTORS IS EXPRESSED IN
PRIMARY SENSITIVE NEURONS
- α1-adrenoceptor produces excitation -neurosecretion.
- α1-adrenoceptor produces irritatation/pain
α1-adrenoceptor produces Neurogenic Inflammation

27. MANAGEMENT OF CHRONIC PROSTATITIS
• Antibiotics such as Fluoroquinolones
• Alpha-blockers with or without antibiotics
• NSAIDs
• Allopurinol
• Finasteride
• Pentosan
• Mepartricin
• Amitryptiline
• Analgesics, including centrally effective drugs
• Muscle relaxants such as Valium or Baclofen
• Phytotherapy
• Physiotherapy with biofeedback
• Thermotherapy and TUNA
• Prostatic massage
• Perineal skin application of Capsaicin
• Sacral and pudendal neuromodulation

28. MANAGEMENT OF CP/CPPS: AN
EVIDENCE BASED APPROACH
(Dimitrakov et Al,Urology,2006)

29. MANAGEMENT OF CP/CPPS: AN
EVIDENCE BASED APPROACH
(Dimitrakov et Al,Urology,2006)

30. ALPHA-BLOCKERS IN CP/CPPS
• Block of alfa-1 receptors in bladder neck (theory of bladder neck
hypertrophy) or block of alfa-1 receptors in sensitive neurons
(theory of neurogenic inflammation)?
(Hruz et Al, Eur Urol,2003); (Wesselmann,World J Urol,2001)
• Three of four trials RCTs showed statistically significant benefits on
symptoms control and modest clinical efficacy
(Mehik et Al, Urology, 2003; Cheah et Al., J urol, 2003; Nickel et al, J Urol, 2004)
• One study failed to show benefit from alpha-blocker therapy (it
enrolled men with long-standing and refractory symptoms)
( Alexander et Al, Ann Intern Med., 2004)

31. ΑLPHA1-ADRENOCEPTORS AND NEUROGENIC
INFLAMMATION IN CP/CPPS
Bladder
Urethra Irritative stimulus
Prostate (Cyclophosphamide)
Dorsal Marrow
Alpha-blocker
α1
SP SP c-fos
Neurogenic CGRP
CGRP Irritation
Inflammation Glutammato/aspartato pain
Restoration of physiological condition
Alfa-1 receptors are not only present on bladder neck but also on the primary
sensitive neurons of the bladder and of the prostate too  the action in CP/CPPS
seems indipendent by the hydraulic fact (Kindly by Geppetti, 2006)

32. CAPSAICIN: TOPICAL APPLICATION TO THE
PERINEAL SKIN
• Implicated in neurogenic inflammation: interacts with
vanilloid receptors (TRPV1)
• Pilot study on 22 patients and 6 healthy control subjects.
• Topical application of 5 ml CAPSAICIN at a
concentration of 10(-5)M to the perineal body skin
• The patients with CP/CPPS reported:
– heat/burning sensation intensity statistically greater than healthy
controls (p<0.001)
– shorter time to heat sensation onset (p<0.001)
– improvement of symptoms after 7 days in 16/22 patients (NIH-
CPSI p<0.01)
(Turini et Al, Urology,2006)

33. ANTIBIOTICS FOR CP/CPPS
A) 2 large-scale studies: a) LVX vs placebo
b) CIPRO vs placebo
(80 + 169 enrolled patients for 6 weeks of treatment)
showed no significant difference in the decrease of NIH-CPSI total
score from baseline to 6 weeks for the two drugs compared with
placebo
(Nickel, BJU,2003; Alexander, Ann Intern Med, 2004)
B) Preliminary experience with therapy designed to eliminate nanobacteria
(comET = tetracycline 500mg + nutriceutical + EDTA suppository)
resulted in significant improvement in the symptoms of recalcitrant
CPPS in the majority of men with CP/CPPS and prostate stones
(Shoskes et Al, J Urol, 2005)

34. ANTI-INFLAMMATORY TARGETS AND PREVENTION OF PCa
• Cytokines
Anti-inflammatory cytokines (Interleukin-12)
• NF-kB
Salicylates
• COX-2
Non-steroidal anti-inflammatory drugs
Selective COX-2 inhibitors
• PPARg
Prostaglandins
Thiazolidinediones (e.g., troglitazone, etc)
• Reactive Oxygen Species
Anti-oxidants: vitamin E, b Carotene
Phytochemicals/free radical scavengers

35. NON-STEROIDAL ANTI-INFLAMMATORY DRUGS
AND RISK FOR PROSTATE CANCER
• Among the prospective studies the relative risk of prostate cancer
for aspirin and non aspirin NSAIDs use ranges from 0.45 for
multiple daily use to 1.05 for twice or more per week
(Roberts et
Al, Mayo Clin Proc, 2002
Leitzmann et al, Cancer Epidemiol Biomarkers Prev,2002; Dasgupta et Al, Cancer J, 2006)
• In Baltimore Longitudinal Study of Aging only men < 70 years old
who had ever used aspirin or ibuprofen had a statistically
significant lower risk of prostate cancer (RR = 0,76 and 0.79
rispecrively). No difference statistically significant in men > 70’
Cancer Epidemiol Biomarkers &
Prev, 2005)
• In Italian multicentric case control study odds ratio (OR) for
regular aspirin use was 1,10 = no protective role of regular aspirin
use is observed on prostate cancer risk

36. NON-STEROIDAL ANTI-INFLAMMATORY DRUGS
(SELECTIVE COX-2 INHIBITORS )
Rofecoxib, Celecoxib, Valdecoxib, Parecoxib,
Etoricoxib and Lumiracoxib
• Only one trial with Rofecoxib 25 and 50 mg for six weeks
in the treatment of CP/CPPS (161 patients)
• Only 50 mg reached statistical significance (symptoms,
pain and quality of life) versus placebo
(Nickel et Al, J Urol,2003)
• Adverse effects on renal events and arrhytmia have been
controversial, with suggestion of a class effect
(Zhang et Al, JAMA 2006)

37. ADVERS EFFECTS OF COX-2 INHIBITORS
• 14 trial reports with 116094 participants
• 6394 composite renal events and 286 arrhythmia events
• Compared with controls Rofecoxib was associated with increased
risk of arrhythymia ( RR=2,90) and renal events (RR=1,53):
removed from the marketplace (2004)
• Celecoxib was associated with lower risk of renal dysfunction
(RR=0.61) compared with controls but the risk of cardiovascular
events may be increased
• Valdecoxib: increased risk of cardiovascular adverse events and
increased risk of serious skin reactions: removed from marketplace
(2005)
• Other agents of same family were not significantly associated with
risks of adverse events
(Zhang et Al. JAMA, 2006)

38. PHYTOTHERAPY: QUERCETINE
• Poliphenolic bioflavonoid (red wine, green tea, onions and spices)
• Antioxidant and anti-inflammatory properties: inhibits IL-8 and
MCP-1 (Monocyte chemoattractant protein-1) and inhibits the
activation of NF-kB by TNF-alpha implicated in CPPS pathogenesis
• 30 patients vs placebo
• 500 mg 2 times daily ( 1 month)
• 67% vs 20% had improved more than 25% in symptoms;
• Significant improvement in 82% if Quercetine is associated with
bromelain and papain (open label)
• Interaction with Quinolones (competitive inhibitor of DNA gyrase)
(Shoskes et Al. Urology,1999)

39. ALLOPURINOL FOR CHRONIC PROSTATITIS
Reflux of urine into prostatic ducts causes prostatic inflammation via high
concetration of purine and pyrimidine base-containing metabolites in
prostatic secretions
(Persson et al, J Urol. 1996)
• Allopurinol is used hoping to lower prostatic levels of uric acid and
improving symptoms
• Only one trial with 54 men met study inclusion criteria
• There was a statistically significant change favoring allopurinol in patient-
reported discomfort between the study and control group at follow-up
• No side effects in patients receiving allopurinol
(McNaughton Collins and Wilt, The Cochrane Librrary, 2006)

40. MEPARTRICIN
• One study examined efficacy of 40 mg of mepartricin, an
estrogen-lowerihg agent, versus placebo in 26 CPPS
patients
• Following 60 days of treatment there was statistically
significant decrease in total NIH-CPSI, pain, quality of
life and 17-beta estradiol levels
• Compared to baseline, the changes in urinary scores and
the serum level of LH, FSH and T at the end of the study
failed to reach statistical significance
(De Rose et Al., Urology, 2004)

41. PENTOSAN POLYSULFATE
• 100 men with CP/CPPS were randomised to 300mg PPS
or pacebo 3 times daily for 16 weeks
• Clinical Global Improvement (CGI)showed moderate to
marked improvement in significantly more PPS-trated
patients (18 or 37% vs. 8 or 18%, p=0,04)
• At 16 weeks also NIH-CPSI scores were significantly
better in the PPS as compared to the placebo group
(-2,0 or 22% vs. -1.0 or 12%, p=0,031)
( Nickel et Al., J Urol., 2005)

42. PHYTOTHERAPY: BEE POLLEN (CERNILTON)
Experimental study in rats show inhibitory effect on the
prostatic inflammatory cytokynes
(Asakawa et Al, Hinyokika Kiyo, 2001)
Clinical study on 90 patients
• 1 tab 3 times daily for 6 months
• If complicating factors: minimal response
• If uncomplicated patients: 36% cured and
42%improved, with decrease in complement
C3/coeruloplasmine in the ejaculate
(Rugendorffet Al. Br.J Urol. 1993)

44. MULTIMODAL THERAPY FOR CP/CPPS
• Monotherapy resulted very often in frustrating answers
• The relative efficacy of diverse therapeutical approaches
suggests that CP/CPPS is a multifactorial condition with
symptoms potentially due to infection, inflammation and/
or neuromuscolar spasm
• An approach using stepwise therapy with antibiotics,
anti-inflammatories and neuromuscolar agents can be
successful in the majority of patients with long-standing
chronic prostatitis
(Shoskes et Al. J Urol. 2003)

45. CATEGORY IV PROSTATITIS
Finding of leukocytes in EPS/VB3 or inflammation in histhologic
specimens
• What is its prevalence:
- in the context of BPH ?
- in prostatic biopsies ?
- in the global population ?
• Can it influence PSA levels ?
• Does it respond to antibiotics ?
• Do we need to treat?

46. CATEGORY IV PROSTATITIS
EPS/VB3 32,2 – 42%
(Potts, 2000; Carver, 2003)
BPH 43,1 – 100%
(Nickel et Al. BJU Int. 1999)
BIOPSIES 40 - 95%
(Stancick,2004; Shattermann et Al, 2003)
RADICAL PROSTATECTOMIES 95%
(Gerstenbluth et Al, J Urol, 2002)
In Japan, where PCa prevalence is very low, only 11,2% of screened
population for high PSA has hystologic evidence of NIH IV prostatitis
( Shimomura et Al, 2003)

47. PATTERNS OF INFLAMMATION IN BPH
• 162 consecutive TURP/open prostatectomy
• 98.1% focal inflammation
• 7 categories of inflammation:
- segregated glandular
- periglandular
- diffuse stromal
- isolated stromal
- lymphoid nodular
- acute necrotizing
- granulomatous
Kohnen PW et al, J Urol 1979

48. PATTERNS OF INFLAMMATION IN BPH
Segregated glandular prostatitis Periglandular prostatitis Diffuse stromal prostatitis
Periglandular and stromal prostatitis Lymphoid nodular prostatitits Acute necrotizing prostatitis

49. (TURP) (44% bacterial growth)

51. PROSTATE INFLAMMATION AND PSA
• There is controversy on the grade of influence of prostatitis
category IV on the serum PSA levels
• Serum PSA levels influenced by:
- extension of the prostate inflammation
- intensity and grade of epithelial lesion
- type of inflammation
Schattermman PHF et al. – Eur Urol 2000;37:404-412
Morote J et al. – Eur Urol 2000;37:537-540

52. PROSTATIC INFLAMMATION AND PSA:
THE IRANI’S SCALE
Extent Infiltration aggressiveness PSA elevation
0 no phlogistic cells no contact between +/-
phlogistic cells and
glandular epithelium
1 diffuse stromal contact between
infiltration/no inflammatory infiltrate +/-
limphoid nodules and glandular epithelium
2 limphoid nodules diffuse stromal infiltration
not aggregated with disruption <25% +
of glandular epithelium
3 wide inflammatory disruption > 25% ++
areas of aggregated of glandular epithelium
infiltration
Irani et Al. J Urol. 1997

53. ASYMPTOMATIC PROSTATITIS NIH-IV
Synthesis of clinical studies
• 7 clinical studies on more than 450 cases with high PSA and
normal DRE and urinalysis
• In all of the 7 studies Quinolones were used +/-NSAIDs
• Reduction of PSA: > 50% of cases
• Mean/median PSA reduction: 16-42%
• PSA normalization: 17-46% only in benign conditions
• PSA specificity: increased
• Number of biopsies reduction: > 20% of cases
( Potts, J Urol, 2000; Carver et Al. J Urol, 2003;
Guercio et Al. Arch It Urol
Androl, 2004)

54. ASYMPTOMATIC PROSTATITIS
DO WE NEED TO TREAT?
Potential benefits:
decrease need for prostate biopsies
potential to decrease BPH or CaP risk
potential to increase fertility (infertile men)
Potential disadvantages:
no proven therapy
potential toxicity of therapy for asymptomatic
patients

55. DIETARY INTAKE OF ANTIOXIDANTS
Intake of different antioxidants that might attenuate cell
and genome damage inflicted by inflammatory oxidants (eg
superoxide, nitric oxide and peroxynitrite) has been found
to protect against prostate cancer development
RCT of SELENIUM supplementation revealed a decrease in incident prostate
cancer (RR 0,51) while ALFA-TOCOFEROL supplementation showed a 32%
decrease in PCa incidence and a 41% decrease in PCa mortality
( Duffield-Lillico at Al, BJU Int,2003)
(The Alpha- Tocoferol, Beta Carotene Ca Prevention study Group, N Engl J Med, 1994)
Consumption of vegetables containing the carotenoid LYCOPENE and
consumption of crociferous vegetables containing isothiocyanates such as
SULFORAPHANE reduce prostate cancer risk, acting as antioxidants by
inducing a plethora of carcinogen detoxification enzymes
(Cohen et Al, J Natl Cancer Inst, 2000; Dinkova-Kostova et Al, Free Radic Biol med, 2000)
CURCUMIN showed free radical scavernging ability and antioxidant
efficiency in experimental study
(Khopde et Al. Biophys Chem. 1999)

56. ROTATION DIET IN FOOD INTOLERANCE
• Minimal persistent prostate inflammation with increased production
of endogenous free radicals could be due to daily intaking of
intolerant foods.
(Sampson, J allergy Clin Immunol, 2004)
• IgE studies can be used to detect real allergies while DRIA test
(Dinamometric Research Into Allergies) can discovery individual
food-intolerance
( Speciani et al, Allergy, 1992)
• Rotation diet can re-establish the food tolerance, reduces
cholesterol and positively increases the LAG-TIME (an in-vitro test
which exprimes the resistance to oxidative stress).
This prove the strong relationship between oxidative stress and diet
(Perrone et Al, 2003)

57. CONCLUSIONS
• Additional well designed basic, clinical and
epidemiological studies are needed to resolve whether
intraprostatic chronic inflammation is a rational target
for prostate cancer prevention
• If so, prostatic infections could be cleared with
antibiotics or antiviral agents, inflammation could be
inhibited by antiinflammatory agents, and reactive
byproducts of the inflammatory response could be
quenched by dietary and supplemental antioxidants
• Also, novel therapies could be developed that interfere
with the intraprostatic production or action of cytokines

58. THANK YOU FOR YOUR
ATTENTION