Multidisciplinary approach to prostatitis.

The modern clinical research on prostatitis started with the work of Stamey and coworkers who developed the basic principles we are still using. They established the segmented culture technique for localizing the infections in the males to the urethra, the bladder, or the prostate and to differentiate the main categories of prostatitis. Such categories with slight modifications are still used according to the NIH classification: acute bacterial prostatitis, chronic bacterial prostatitis, Chronic Pelvic Pain Syndrome (CPPS) and asymptomatic prostatitis. Prostatic inflammation is considered an important factor in influencing both prostatic growth and progression of symptoms of benign prostatic hyperplasia and prostatitis. Chronic inflammation/neuroinflammation is a result of a deregulated acute phase response of the innate immune system affecting surrounding neural tissue at molecular, structural and functional levels. Clinical observations suggest that chronic inflammation correlates with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and benign prostatic hyperplasia (BPH) and an history of clinical chronic prostatitis significantly increases the odds for prostate cancer. The NIHNIDDK classification based on the use of the microbiological 4- glasses localization test or simplified 2-glasses test, is currently accepted worldwide. The UPOINT system identifies groups of clinicians with homogeneous clinical presentation and is used to recognize phenotypes to be submitted to specific treatments. The UPOINTS algorithm implemented the original UPOINT adding to the urinary domains (U), psycho-social (P), organspecific (O), infection (I), neurological (N), muscle tension and tenderness (T) a further domain related to sexuality (S). In fact sexual dysfunction (erectile, ejaculatory, libido loss) has been described in 46-92% of cases with a high impact on the quality of life of patients with CP/CPPS. Prostatic ultrasound represents the most popular imaging test in the work-up of either acute and chronic prostatitis although no specific hypo-hyperechoic pattern has been clearly associated with chronic bacterial prostatitis and CPPS. Use of a digital-processing software to calculate the extension of prostatic calcification area at ultrasound demonstrated a higher percentage of prostatic calcification in patients with chronic bacterial prostatitis. Multiparametric Magnetic Resonance Imaging (mpMRI) is the current state-of-the art imaging modality in the assessment of patients with prostate cancer although a variety of benign conditions, including inflammation, may mimic prostate cancer and act as confounding factors in the discrimination between neoplastic and non-neoplastic lesions. Bacteria can infect prostate gland by: ascending the urethra, reflux of urine into the prostatic ducts, direct inoculation of bacteria through inserted biopsy needles or hematogenous seeding. Enterobacteriaceae are the predominant pathogens in acute and chronic bacterial prostatitis, but an increasing role of Enterococci has been reported. Many strains of these uropathogens exhibit the ability to form biofilm and multidrug- resistance. Sexually Transmitted Infections (STI) agents, in particular Chlamydia trachomatis and Mycoplasma genitalium, have been also considered as causative pathogens of chronic bacterial prostatitis. On the contrary the effective role in genital diseases of other "genital mycoplasmas" is still a much debated issue. Sexually Transmitted Infections agents should be investigated by molecular methods in both patient and sexual partner. "Next generation" investigations, such as cytokine analysis, cytological typing of immune cells could help stratifying the immune response. Epigenetic dysregulation of inflammatory factors should be investigated according to systemic and compartment-specific signals. The search for biomarkers should also include evaluation of hormonal pathways, as measurement of estrogen levels in semen. Antimicrobials are the first line agents for the treatment of bacterial prostatitis. The success of antimicrobial treatment depends on the antibacterial activity and the pharmacokinetic characteristics of the drug which must reach high concentrations in prostate secretion and prostate tissue. Acute bacterial prostatitis can be a serious infection with a potential risk for urosepsis For iInitial treatment of severely ill patients, intravenous administration of high doses of bactericidal antimicrobials, such as broad-spectrum penicillins, third-generation cephalosporins or fluoroquinolones, is recommended in combination with an aminoglycoside. Use of piperacillin-tazobactam and meropenem is justified in presence of multiresistant gramnegative pathogens. The antibiotic treatment of chronic prostatitis is currently based on the use of fluoroquinolones that, given for 2 to 4 weeks, cured about 70% of men with chronic bacterial prostatitis. For the treatment of Chlamydial prostatitis macrolides were shown to be more effective than fluoroquinolones, whereas no differences were observed in microbiological and clinical efficacy between macrolides and tetracyclines for the treatment of infections caused by intracellular pathogens. Aminoglycosides and fosfomycin could be considered as a therapeutic alternative for the treatment of quinolone resistant prostatitis. Use of alpha-blockers in CP/CPPS patients with urinary symptoms and analgesics +/- non steroidal anti-inflammatory drugs (NSAID), in presence of pain demonstrated a reduction of symptoms reduction and an improvement of quality of life, although long term use of NSAID is limited by side effect profile. However, the multimodal therapeutic regimen by contemporary use of alphablockers, antibiotics and anti-inflammatory showed a better control of prostatitis symptoms than single drug treatment. Novel therapeutic substances for the treatment of pain, such as the cannabinoid anandamide would be highly interesting to test. An alternative for the treatment of chronic prostatitis/chronic pelvic pain syndrome is phytotherapy, as primary therapy or in association with other drugs. Quercetin, pollen extract, extract of Serenoa repens and other mixtures of herbal extracts showed a positive effect on symptoms and quality of life without side effects. The association of CP/CPPS with alterations of intestinal function has been described. Diet has its effects on inflammation by regulation of the composition of intestinal flora and direct action on the intestinal cells (sterile inflammation). Intestinal bacteria (microbiota) interacts with food influencing the metabolic, immune and inflammatory response of the organism. The intestinal microbiota has protective function against pathogenic bacteria, metabolic function by synthesis of vitamins, decomposition of bile acids and production of trophic factors (butyrate), and modulation of the intestinal immune system. The alteration of the microbiota is called "dysbiosis" causing invasive intestinal diseases pathologies (leaky gut syndrome and food intolerances, irritable bowel syndrome or chronic inflammatory bowel diseases) and correlating with numerous systemic diseases including acute and chronic prostatitis. Administration of live probiotics bacteria can be used to regulate the balance if intestinal flora. Sessions of hydrocolontherapy can represent an integration to this therapeutic approach. Finally, microbiological examination of sexual partners can offer supplementary information for treatment.

Clinical outcomes in adults' subjects with aphthous stomatitis treated with an oral hyaluronic acid-based medical device.

BACKGROUND: Oral mucosal ulcers are quite common in an otherwise healthy population and can determine a real worsening of the quality of life. Conventional therapy is not appropriate since ulcers often recur and, even if not needed, therapy lasting not less than 2-3 weeks carries a high risk of serious side effects. The use of hyaluronic acid applied as an adhesive gel over the lesions seems to have potential in terms of efficacy and the avoidance of side effects. Of course, hyaluronic acid-based formulations show different effects and tolerability. METHODS: In our study, we retrospectively reported the results obtained using a medical device, Bloxaphte® (Bausch & Lomb, Macherio, Monza-Brianza, Italy), applied for 14 days to counteract ulcers in adults. RESULTS: Treatment with the HA-based oral gel determined better results both in terms of the number of oral lesions and in terms of lesion sizes. Regarding the number of lesions, the results are significant even after 6 days of treatment, while 3 days are enough to differentiate the two groups with respect to lesion sizes. CONCLUSIONS: Our data clearly demonstrate the healing capability and safety profile of the product in reducing the number and size of the ulcers within the first week of daily application.

Role of a berberine-based nutritional supplement in reducing diarrhea in subjects with functional gastrointestinal disorders.

BACKGROUND: Berberine, an alkaloid obtained by extraction from Berberis spp., is a botanical that is widely used in the nutraceutical sector to control cholesterol and blood glucose levels. It is also a molecule that is effective in limiting diarrhea due to its multi-factorial properties, including its antimicrobial, gut eubiotic and antisecretive actions, and its ability to slow gut motility. In our routine clinical practice, we have suggested the use of a berberine-based nutraceutical, formulated with melatonin and depolymerized guar gum, to patients affected by functional diarrhea (FD) or by diarrhea-type irritable bowel syndrome (IBS-D). METHODS: We have therefore retrospectively analyzed the clinical effect of such a nutritional supplement in these two sub-groups of patients. RESULTS: Despite the highly pragmatic scheme of our study, our findings strongly confirm the antidiarrheal properties of berberine and recommend its use in some gut functional diseases characterized by frequent evacuation of mushy and/or watery stools. In fact, even after 30 days of treatment, the berberine-based nutritional supplement significantly reduces diarrheal events by 50-70%. After 90 days, this reduction improves to between 70 and 80%, with a reduction of more than 60% in the number of evacuations per week and with more than 50% of treated subjects demonstrating normalized, according to self-reported Bristol Stool Scale categorization, stool consistency. The product is well tolerated and adherence to the proposed therapy is good. Common side effects of the product are flatulence and meteorism, likely due to the "acarbose-like" berberine effects on gut α-glucosidase. CONCLUSIONS: Patients, especially those preferring "natural" therapy, can be successfully treated, when affected by a gut functional disease characterized by diarrhea, by berberine-based products.

Vulvovestibular Syndrome and Vaginal Microbiome: A Simple Evaluation.

BACKGROUND: The vulvovestibular syndrome (VVS) is a chronic, inflammatory, multifactorial, chronic inflammation of the female urogenital access. METHODS: The aim of this anecdotal, observational, retrospective, case-control study was to comparatively evaluate the most common bacterial strains (Lactobacillus spp., Klebsiella spp., Gardnerella spp., and Streptococcus spp.) and fungi (Candida spp., Pennicillum spp., and Aspergillus spp.) in vulvodinic women, and in women without gynecological symptoms (control group). RESULTS: We found that vulvodinic patients had statistically lower Lactobacilli and higher total Fungi concentration. CONCLUSIONS: Our preliminary study is useful to further clarify the etiopathology of vulvodynia and suggest new therapeutic strategies for approaching the VVS.