ADVANCES IN UROLOGICAL DIAGNOSIS AND IMAGING
A dvA nces in U rologic A l d i Agnosis A
EDITOR in CHIEF
Pietro Cazzola (Pathologyst), Milan (Italy)
CO-EDITORS
Donatella Tedeschi (Pathologyst), Milano (Italy)
Konstantinos Stamatiou (Greece)
EDITORIAL BOARD
Ahmed Hashim, London (Great Britain)
Ali Tamer, Cairo (Egypt)
Benatta Mahmoud, Oran (Algeria)
Bhatti Kamran Hassan, Alkhor (Qatar)
Cheng Liang, Indianapolis (USA)
Fragkiadis Evangelos, Athens (Greece)
Gül Abdullah, Bursa (Turkey)
Jaffry Syed, Galway (Ireland)
Kastner Christof, Cambridge (Great Britain)
Lopez-Beltran Antonio, Lisbon (Portugal)
Salomon George, Hamburg (Germany)
Waltz Joachen, Marseille (France)
Wijkstra Hessel, Eindhoven (Netherlands)
General Information
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Contents
2. Asymptomatic chronic bacterial prostatitis causing recurrent cystitis to the female sexual partner. Apropos of three cases. Konstantinos Stamatiou, Marios Ioannou, Christina Louka, Nektaria Rekleiti
5. Medical Management of Lower Urinary Tract Symptoms Attributed to Benign Prostatic Hyperplasia: from AUA Guidelines
6. Association of dietary elements and lower urinary tract symptoms
7. Prostate Microbiota and Prostate Cancer
8. Clinical Applications of the Gut Microbiome in Genitourinary Cancers
9. Food additive emulsifiers and cancer risk: Results from the French prospective NutriNet-Santé cohort
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Asymptomatic chronic bacterial prostatitis causing recurrent cystitis to the female sexual partner. Apropos of three cases.
Konstantinos Stamatiou1, Marios Ioannou1, Christina Louka2, Nektaria Rekleiti2
1 Urology Department, Tzaneio General Hospital, Piraeus, Greece
2 Microbiology Department, Tzaneio General Hospital, Piraeus, Greece
SUMMARY The term sexually transmitted infections is currently limited to describe infections caused by, Chlamydia, Neisseria gonorrhoeae, Treponema pallidum, and the viruses of Herpes and the Human Condyloma Virus. However typical organisms such as Escherichia coli may also cause sexually transmitted infections of urinary tract. Although mediated by sexual intercourse, recurrent cystitis is not considered sexually transmitted since pathogens are believed to be part of the vaginal and/or perineal flora.
i ntrod U ction
Simple cystitis is common among women, even among young, healthy women who have anatomically and physiologically normal urinary tracts more than 50% of women will experience at least one urinary tract infection (UTI) in their life. In fact, women are particularly susceptible due to the close proximity of the rectum to the urethral meatus as well as the relatively short urethral length in females. Half of patients will experience recurrent UTIs (1). Known risk factors for recurrent UTI include diabetes, functional disability, sexual intercourse, history of urogynecological surgery, incomplete bladder emptying, accidental bowel leakage, urinary incontinence and menopause (2). Additional to the above, sex induced UTIs, have been associated with use of spermicidal products, having a first UTI at an early age, and having a maternal history of UTIs. Some factors thought to predispose to recurrent UTI in women, such as pre- and post-coital voiding patterns, frequency of urination, wiping patterns, and douching have not been proven to be risk factors for UTI (3). Although mediated by sexual intercourse they are not considered sexually transmitted since pathogens are believed to be part of the vaginal and/or perineal flora (4). On the other hand, chronic prostatitis is a relatively uncommon health condition in men. It is not considered a sexually transmitted disease (STD) however,
Similarly, chronic prostatitis is also not considered a sexually transmitted disease although is frequently caused by bacterial infections following sexual intercourse. In this paper we present 3 cases of recurrent cystitis in otherwise healthy premenopausal women attributed to asymptomatic chronic bacterial prostatitis of the male sexual partner.
Key words: sexual intercourse; chronic prostatitis; recurrent cystitis.
is frequently caused by bacterial infections following sexual intercourse which can’t be passed back to sexual partner (5). In this paper we present 3 cases of recurrent cystitis in otherwise healthy premenopausal women attributed to asymptomatic chronic bacterial prostatitis of the male sexual partner.
c A se report
All three cases were presented with symptoms of urinary urgency, often associated with urinary incontinence, whose onset was within 2-12 hours after sexual intercourse. Despite proven bacterial eradication, recurrences occurred within one month after treatment. While no prophylactic countermeasure -including low dose antibiotics- was effective in preventing recurrences, absence of sexual activity resulted in disappearance of UTIs.
The diagnosis of acute UTI was made using a combination of the symptom assessment and urine diagnostic studies (4). Male sexual partners were evaluated with the four-glass test (Meares-Stamey).
In all three cases, sexual transmission of uropathogens has been demonstrated by identifying identical E. coli in the expressed prostate secretion and/or urine sample after prostatic massage of sexual partners. Following
30 days quinolones-based treatment, male sexual partners were evaluated again with the four-glass test. All three were found bacteria free. None of the women patients was found with UTI during 6 month follow up. Demographics and medical history of the three patients are presented in details in the Table
d isc U ssion
General consideration about sexually induced UTIs, is that they are most common in premenopausal women, they are caused by specific pathogens, are recurrent (while caused by a new pathogen each time) and occur at short intervals. The exact pathogenetic mechanism for the development of recurrent infections associated with sexual intercourse is not known. Furthermore, it is not known if women having recurrent sex-induced infections represent a separate population, compared to those who present an isolated infection. According to the literature re-infections in women, are mainly associated with increased vaginal mucosal receptivity for uro-pathogens (6). This is probably due to a greater propensity for uropathogenic coliforms to adhere to uroepithelial cells. The origin of such pathogens could be multiple: In part they could represent a sufficient number of virulent bacterial populations growing in the vaginal flora. Due to the use of vaginal cleaners/ antiseptics, antibiotics, etc that cause changes in the
K. Stamatiou, M. Ioannou, C. Louka, N. Rekleiti
vaginal microflora (loss of lactobacilli) they colonize periurethral tissues (7).
On the other hand, the causing pathogens could derive from host contamination by the sexual partner and not from disorders of the common vaginal and urethral flora. Sexual transmission of uropathogens has been demonstrated by identifying identical E. coli in the faecal and urinary flora of sexual partners (8).
Accounting for approximately 75% to 95% of cases, Escherichia coli is the most common etiologic agent in uncomplicated UTIs in women. Older studies of recurrent UTI using phenotypically based typing methods or less specific DNA based typing methods, found that recurrent UTIs are mainly attributable to reinfection with new strains. However, applying pulsed-field gel electrophoresis (PFGE) and culture results newer studies showed that 77% of recurrent UTIs were caused by a relapse with the primary infecting Escherichia coli (9). This fact may suggest that the infected prostatic secretion may represent stable reservoirs for recurrent UTIs.
To our knowledge almost all current guidelines on recurrent UTIs are focusing on preventative strategies (10). Therefore, future guidelines should consider recommendations to assist management of complex patient groups, such as persistent recurrent sexually induced UTI. In such a case systematic investigation of asymptomatic carriers among sexual partners of the patient may reveal a novel perspective on recurrent UTIs pathophysiology and treatment.
49 yo., sexually active advanced socio-economical level tertiary education
No significant medical history exept: frequent UTIs, which respond to UTI antibiotics
32 yo., sexually active median socio-economical level tertiary education
No significant medical history exept: frequent UTIs, often associated with intercourse, variable response to UTI antibiotics
23yo., sexually active median socio-economical level tertiary education
No significant medical history exept: frequent UTIs, associated with intercourse, which respond to UTI antibiotics
4 positive urine cultures for 10,000–50,000 CFU/ml E. coli, in last 7 months
Normal findings in CE and Imaging
No post-void residual
3 positive urine culture for 10,000–100,000 CFU/ml E. coli,
2 negative urine cultures in last 12 months
Normal findings in CE and Imaging
No post-void residual
3 positive urine cultures for 100,000 CFU/ml E. coli, in last 6 months
Normal findings in CE and Imaging
No post-void residual
• Vaginal estrogen
• D-mannose
• Vitamin C
• Hydratation Free of symptoms
• Probiotics and vaccines
• Post-coital antibiotics
Free of symptoms
• Phytotherapy
• Post-coital antibiotics
Free of symptoms
Stamatiou, M. Ioannou, C. Louka, N. Rekleiti
r eferences
1. Foxman B Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. Am. J. Med 113 Suppl, 5S–13S (2002).
2. Georgakopoulos G, Stamatiou K, Ilias G, Karanasiou V, Christakis M, Matsagoura M. et al. Sex-induced cystitis: An epidemiological study in female populations of three district of rural Thebes, Greece. Indian J Sex Transm Dis. 2007;28:79-82
3. Hooton TM. Recurrent urinary tract infection in women. Int J Antimicrob Agents. 2001 Apr;17(4):259-68.
4. Stamatiou K, Panagopoulos P, Petrakos G, Economou A, Lycoudi A. Sex-induced cystitis--patient burden and other epidemiological features. Clin Exp Obstet Gynecol. 2005;32(3):180-2.
5. Magri V, Boltri M, Cai T, Colombo R, Cuzzocrea S, De Visschere P, et al. Multidisciplinary approach to prostatitis. Arch Ital Urol Androl. 2019;90 (4):227-248.
6. Nicolle L. Epidemiology of urinary tract infections. Infect Med. 2001;18:153-62
7. Stamatiou C, Petrakos G, Bovis C, Panagopoulos P, Economou A, Karkanis C. Efficacy of prophylaxis in women with sex induced cystitis.Clin Exp Obstet Gynecol. 2005;32(3):193-5.
8. Foxman B, Zhang L, Tallman P, Andree BC, Geiger AM, Koopman JS, et al. Transmission of uropathogens between sex partners. J Infect Dis. 1997;175:989-92.
9. Ejrnæs K. Bacterial characteristics of importance for recurrent urinary tract infections caused by Escherichia coli. Dan Med Bull. 2011;58(4):B4187.
10. Kwok M, McGeorge S, Mayer-Coverdale J, Graves B, Paterson DL, Harris PNA, et al. Guideline of guidelines: management of recurrent urinary tract infections in women. BJU Int. 2022;130 Suppl 3(Suppl 3):11-22
C orresponden C e Konstantinos Stamatiou, MD Afendouli 1, 18536, Piraeus, Greece E-mail: stamatiouk@gmail.com
Medical Management of Lower Urinary Tract Symptoms Attributed to Benign Prostatic Hyperplasia: from AUA Guidelines
Sandhu JS, Bixler BR, Dahm P, Goueli R, Kirkby E, Stoffel JT, Wilt TJ. Management of Lower Urinary Tract Symptoms Attributed to Benign Prostatic Hyperplasia (BPH): AUA Guideline Amendment 2023. J Urol. 2024 Jan;211(1):11-19.
This AUA guideline is provided free of use to the general public for academic and research purposes.
Benign prostatic hyperplasia (BPH) is a histologic diagnosis that refers to the proliferation of smooth muscle and epithelial cells within the prostatic transition zone. The prevalence and the severity of lower urinary tract symptoms (LUTS) in the aging male can be progressive.
evA lUAtion
Initial Evaluation
1. In the initial evaluation of patients presenting with bothersome LUTS possibly attributed to BPH, clinicians should obtain a medical history, conduct a physical examination, utilize the International Prostate Symptom Score (IPSS), and perform a urinalysis. (Clinical Principle)
2. Patients should be counseled on options for intervention, which can include behavioral/lifestyle modifications, medical therapy and/or referral for discussion of procedural options. (Expert Opinion)
Follow-up Evaluation
3. Patients should be evaluated by their providers 4-12 weeks after initiating treatment (provided adverse
events do not require earlier consultation) to assess response to therapy. Revaluation should include the IPSS. Further evaluation may include a post-void residual (PVR) and uroflowmetry. (Clinical Principle)
4. Patients with bothersome LUTS/BPH who elect initial medical management and do not have symptom improvement and/or experience intolerable side effects should undergo further evaluation and consideration of change in medical management or surgical intervention.
medicAl therApy
Alpha Blockers
Clinicians should offer one of the following alpha blockers as a treatment option for patients with bothersome, moderate to severe LUTS/BPH: alfuzosin, doxazosin, silodosin, tamsulosin, or terazosin ( Moderate Recommendation ).
When prescribing an alpha blocker for the treatment of LUTS/BPH, the choice of alpha blocker should be based on patient age and comorbidities, and different adverse event profiles (e.g., ejaculatory dysfunction [EjD], changes in blood pressure) (Moderate Recommendation).
Alpha Blockers and Intraoperative Floppy Iris Syndrome (IFIS)
When initiating alpha blocker therapy, patients with planned cataract surgery should be informed of the associated risks and be advised to discuss these risks with their ophthalmologists.
Alpha Reductase inhibitor (5-ARI)
• For the purpose of symptom improvement, 5-ARI monotherapy should be used as a treatment option in patients with LUTS/BPH with prostatic enlargement as judged by a prostate volume of > 30g on imaging, a prostate specific antigen (PSA) > 1.5ng/mL, or palpable prostate enlargement on digital rectal exam (DRE) (Moderate Recommendation).
• 5-ARIs alone or in combination with alpha blockers are recommended as a treatment option to prevent progression of LUTS/BPH and/or reduce the risks of urinary retention and need for future prostate-related surgery (Moderate Recommendation):
• Before starting a 5-ARI, clinicians should inform patients of the risks of sexual side effects, certain uncommon physical side effects, and the low risk of prostate cancer (Moderate Recommendation).
• Clinicians may consider 5-ARIs as a treatment option to reduce intraoperative bleeding and peri- or postoperative need for blood transfusion after transurethral resection of the prostate (TURP) or other surgical intervention for BPH.
Phosphodiesterase-5 Inhibitor (PDE5)
For patients with LUTS/BPH irrespective of comorbid erectile dysfunction (ED), 5mg daily tadalafil should be discussed as a treatment option. (Moderate Recommendation).
Combination Therapy
• 5-ARI in combination with an alpha blocker should be offered as a treatment option only to patients with LUTS associated with demonstrable prostatic enlargement as judged by a prostate volume of > 30g on imaging, a PSA > 1.5ng/mL, or palpable prostate enlargement on DRE (Strong Recommendation).
• Anticholinergic agents, alone or in combination with an alpha blocker, may be offered as a treatment option to patients with moderate to severe predominant storage LUTS. (Conditional Recommendation).
• Beta-3-agonists in combination with an alpha blocker may be offered as a treatment option to patients with moderate to severe predominate storage LUTS. (Conditional Recommendation)
• Clinicians may offer the combination of low-dose daily 5mg tadalafil with alpha blockers for the treatment of LUTS/BPH (Conditional Recommendation).
• Clinicians may offer the combination of low dose daily tadalafil 5mg with finasteride for the treatment of LUTS/BPH (Conditional Recommendation).
Acute Urinary Retention (AUR) Outcomes
• Physicians should prescribe an oral alpha blocker prior to a voiding trial to treat patients with AUR related to BPH (Moderate Recommendation).
• Patients newly treated for AUR with alpha blockers should complete at least three days of medical therapy prior to attempting trial without a catheter (TWOC).
• Clinicians should inform patients who pass a successful TWOC for AUR from BPH that they remain at increased risk for recurrent urinary retention. (Moderate Recommendation).
Association of dietary elements and lower urinary tract symptoms
Scand J Urol Nephrol. 2000 Feb;34(1):46-50.
A Finnish study, performed twenty years ago, showed that dietary elements are related to lower urinary tract symptoms (LUTS) and thus to diseases causing LUTS. The confounder-adjusted risk of LUTS was 0.68 (95% CI 0.54-0.86) among men consuming vegetables daily compared with men consuming vegetables less frequently. Compared with men who eat meat less frequently, the confounder-adjusted risk of LUTS was 2.08 (95% CI 1.00-4.10) among men consuming meat weekly, and 2.56 (95% CI 1.30-5.02) among men consuming meat daily. The confounder-adjusted risk of LUTS was 0.73 (95% CI 0.58-0.93) among men who consumed butter compared to those who did not.
J Koskimäki, M Hakama, H Huhtala, T L Tammela
Prostate Microbiota and Prostate Cancer
https://pubmed.ncbi.nlm.nih.gov/34956913/
Although the incidence and mortality of prostate cancer have gradually begun to decline in the past few years, it is still one of the leading causes of death from malignant tumors in the world. The occurrence and development of prostate cancer are affected by race, family history, microenvironment, and other factors. In recent decades, more and more studies have confirmed that prostate microflora in the tumor microenvironment may play an important role in the occurrence, development, and prognosis of prostate cancer. Microorganisms or their metabolites may affect the occurrence and metastasis of cancer cells or regulate anti-cancer immune surveillance. In addition, the use of tumor microenvironment bacteria in interventional targeting therapy of tumors also shows a unique advantage. This review introduce the pathway of microbiota into prostate cancer, focusing on the mechanism of microorganisms in tumorigenesis and development, as well as the prospect and significance of microorganisms as tumor biomarkers and tumor prevention and treatment.
Che B, Zhang W, Xu S,Yin J, He J, Huang T, Li W,Yu Y, Tang K. Prostate Microbiota and Prostate Cancer: A New Trend in Treatment. Front Oncol. 2021 Dec 10;11:805459.
Clinical Applications of the Gut Microbiome in Genitourinary Cancers
https://pubmed.ncbi.nlm.nih.gov/38788173/
Recently recognized as one of the hallmarks of cancer, the microbiome consists of symbiotic microorganisms that play pivotal roles in carcinogenesis, the tumor microenvironment, and responses to therapy. With recent advances in microbiome metagenomic sequencing, a growing body of work has demonstrated that changes in gut microbiome composition are associated with differential responses to immune checkpoint inhibitors (ICIs) because of alterations in cytokine signaling and cytotoxic T-cell recruitment. Therefore, strategies to shape the gut microbiome into a more favorable, immunogenic profile may lead to improved responses with ICIs. Immunotherapy is commonly used in genitourinary (GU) cancers such as renal cell carcinoma, urothelial cancer, and to a limited extent, prostate cancer. However, a subset of patients do not derive clinical benefit with ICIs. Gut microbiome-based interventions are of particular interest given the potential to boost responses to ICIs in preclinical and early-phase prospective studies. Novel approaches using probiotic therapy (live bacterial supplementation) and fecal microbiota transplantation in patients with GU cancers are currently under investigation.
Charles B Nguyen, Ulka N Vaishampayan. Clinical Applications of the Gut Microbiome in Genitourinary Cancers. Am Soc Clin Oncol Educ Book. 2024 Jun;44(3):e100041.
Food additive emulsifiers and cancer risk: Results from the French prospective NutriNet-Santé cohort
https://pubmed.ncbi.nlm.nih.gov/38349899/
Emulsifiers are widely used food additives in industrially processed foods to improve texture and enhance shelf-life. Experimental research suggests deleterious effects of emulsifiers on the intestinal microbiota and the metabolome, leading to chronic inflammation and increasing susceptibility to carcinogenesis. However, human epidemiological evidence investigating their association with cancer is nonexistent. This study aimed to assess associations between food additive emulsifiers and cancer risk in a large population-based prospective cohort. This study included 92,000 adults of the French NutriNet-Santé cohort without prevalent cancer at enrolment (44.5 y [SD: 14.5], 78.8% female, 2009 to 2021). They were followed for an average of 6.7 years [SD: 2.2]. Food additive emulsifier intakes were estimated for participants who provided at least 3 repeated 24-h dietary records linked to comprehensive, brand-specific food composition databases on food additives. Multivariable Cox regressions were conducted to estimate associations between emulsifiers and cancer incidence. Overall, 2,604 incident cancer cases were diagnosed during follow-up (including 750 breast, 322 prostate, and 207 colorectal cancers). Higher intakes of mono- and diglycerides of fatty acids (FAs) (E471) were associated with higher risks of overall cancer (HR high vs. low category = 1.15; 95% CI [1.04, 1.27], p-trend = 0.01), breast cancer (HR = 1.24; 95% CI [1.03, 1.51], p-trend = 0.04), and prostate cancer (HR = 1.46; 95% CI [1.09, 1.97], p-trend = 0.02). In addition, associations with breast cancer risk were observed for higher intakes of total carrageenans (E407 and E407a) (HR = 1.32; 95% CI [1.09, 1.60], p-trend = 0.009) and carrageenan (E407) (HR = 1.28; 95% CI [1.06, 1.56], p-trend = 0.01). No association was detected between any of the emulsifiers and colorectal cancer risk. Several associations with other emulsifiers were observed but were not robust throughout sensitivity analyses. Main limitations include possible exposure measurement errors in emulsifiers intake and potential residual confounding linked to the observational design. In this large prospective cohort, we observed associations between higher intakes of carrageenans and mono- and diglycerides of fatty acids with overall, breast and prostate cancer risk. These results need replication in other populations. They provide new epidemiological evidence on the role of emulsifiers in cancer risk.
Laury Sellem, Bernard Srour, Guillaume Javaux, et al. Food additive emulsifiers and cancer risk: Results from the French prospective NutriNet-Santé cohort. PLoS Med 2024 Feb13;21(2):e1004338
