BACKGROUND:The authors elucidated an etiologic role of human papillomavirus (HPV) infection in carcinoma of the bladder. METHODS: One hundred seventeen of 224 patients with bladder carcinoma who were treated between 1997 and 2009 were enrolled in this study. The presence of HPV DNA was tested on frozen carcinoma tissues that were obtained by transurethral resection using a polymerases chain reaction-based method. Localization of HPV was observed on archival tissue specimens by in situ hybridization (ISH) for high-risk HPV DNA. Cyclin-dependent kinase (CDK) inhibitor 2A (inhibits CDK4) (p16-INK4a) and minichromosome maintenance protein-7 (mcm-7)-surrogate markers for high-risk HPV-E7 oncoprotein-and HPV-L1 (capsid) protein expression were evaluated by immunohistochemistry. RESULTS: HPV types 16, 18, 31, 33, 52, and 58, and an unknown HPV type were detected in 18 of 117 samples (15%) from patients with bladder carcinoma. HPV16 was identified in 6 samples, HPV18 was identified in 4 samples, and HPV33 was identified in 3 samples. All were single HPV type infections. HPV was detected in 38% (12 of 28) of histologic grade 1 bladder carcinomas, 8.5% (6 of 71) of grade 2 bladder carcinomas, and in 0% (0 of 18) of grade 3 bladder carcinomas. Multivariate analysis indicated that younger age (<60 years; odds ratio [OR], 10.9; 95% confidence interval [CI], 2.6-45.3) and grade 1 tumors (OR, 4.5; 95% CI, 1.2-17.0) were associated with HPV infection. ISH analysis indicated that high-risk HPV DNA was localized in the nuclei of tumor cells of all HPV-positive samples. p16-INK4a and mcm-7 were expressed in 94% and 89% of HPV-positive carcinoma cells, respectively. HPV-L1 protein expression, which suggested reproductive HPV infection, was not observed in any carcinoma. CONCLUSIONS: The current results indicated that high-risk HPV is likely to be a causative agent of some low-grade bladder carcinomas that develop in younger patients.
Aims To evaluate urinary incontinence using the International Consultation on Incontinence Questionnaire‐Short Form (ICIQ‐SF), daily pad use, and 24‐h pad weight test before and after radical prostatectomy (RP) chronologically, and the correlation between them. Methods ICIQ‐SF and questions on daily pad use provided subjective, and 24‐h pad weight test for objective evaluation. Results In total, 258 cases were recruited. The continence rate at 12 months after RP was 67% for no pad use, 87% for security 1 pad/day, and 94% for 1 pad/day. The median ICIQ‐SF total score before and at 1, 3, 6, and 12 months after RP was 0, 10, 7, 5, and 4, respectively. Incontinence patterns differed when comparing ICIQ‐SF results pre‐ and post‐RP. Significant correlation existed between the ICIQ‐SF total score, 24‐h pad weight test, and daily pad use; however, point distribution on each scatter plot varied widely. Comparing results before and at 12 months after RP revealed complete recovery for 35% of patients from the ICIQ‐SF total score, 67% from daily pad use, and 64% from the 24‐h pad weight test. A combination of all 3 showed a recovery of preoperative levels in 29% of patients. Conclusions ICIQ‐SF was effective and convenient for evaluating UI, including the pattern of UI, after RP. Significant correlation, but wide variations, among ICIQ‐SF, daily pad use, and the 24‐h pad weight test existed. The best evaluation method would be the one that can compare UI status pre‐ and post‐RP using the ICIQ‐SF and 24‐h pad weight test.
BackgroundOropharyngeal squamous cell carcinoma (OSCC) has shown a gradual increase in male predominance due to the increasing incidence of human papillomavirus (HPV)-associated OSCC. However, the mode of HPV transmission to the oral cavity is poorly understood, and little is known about the epidemiology of oral HPV infection in men. The prevalence rates of HPV, Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma spp., and Ureaplasma spp. were compared in the oropharynx (oral cavity) and urine of male Japanese patients attending a sexually transmitted disease clinic.MethodsThe study population consisted of 213 men aged 16 – 70 years old (mean: 34.4 years old). Oropharyngeal gargles and urine were collected, and sedimented cells were preserved in liquid-based cytology solution. After DNA extraction, β-globin and infectious organisms were analyzed by a PCR-based method. The HPV genotype was determined by HPV GenoArray test.Resultsβ-Globin was positive in 100% and 97.7% of oral and urine samples, respectively. HPV detection rates were 18.8% and 22.1% in oral and urine samples, respectively, suggesting that the prevalence of HPV infection in the oral cavity was similar to that in the urinary tract. N. gonorrhoeae was more prevalent in oral (15.6%) than urine samples (9.1%), whereas C. trachomatis was detected more frequently in urine (15.9%) than oral samples (4.2%). The detection rates of M. genitalium, M. hominis, and Ureaplasma spp. were 5.2%, 10.3%, and 16.0% in oral samples, and 7.7%, 6.3%, and 19.2% in urine, respectively. There were no significant differences in the detection rates of Mycoplasma spp. and Ureaplasma spp. between anatomical locations. The distribution of HPV types were similar in oral and urine samples, and HPV16 was the most common type. The majority of men with HPV infection in both the oral cavity and urine had concordant oral and urinary HPV infection. The presence of urinary HPV infection was an independent risk factor of oral HPV infection, with an odds ratio of 3.39 (95% CI: 1.49 – 7.71), whereas oral gonococcal infection was inversely correlated with oral HPV infection (odds ratio: 0.096; 95% CI: 0.01 – 0.77).ConclusionsOral HPV infection commonly occurs in sexually active men, and is significantly correlated with urinary HPV infection.
The status of human papillomavirus (HPV) infection in urothelial inverted papilloma was examined in the present study. Formalin-fixed and paraffin-embedded tissues from eight cases of inverted papilloma of the bladder were studied. The presence of HPV-DNA was examined by modified GP5/6+PCR using archival tissue sections by microdissection. HPV genotype was determined with a Hybri-Max HPV genotyping kit. Immunohistochemical analysis for p16-INK4a, mcm7, HPV-E4, and L1, and in situ hybridization for the HPV genome were performed. HPV was detected in seven of eight cases (87.5%) of inverted papilloma. Three cases were diagnosed as inverted papilloma with atypia, while the remaining five were typical cases. HPV-18 was detected in two cases, including one inverted papilloma with atypia, and HPV-16 was detected in four cases, including one inverted papilloma with atypia. Multiple HPV type infection was detected in one typical case and one atypical case. High-risk HPV was present in all HPV-positive cases. Cellular proteins, p16-INK4a and mcm7, which are surrogate markers for HPV-E7 expression, were detected in all HPV-positive cases, and their levels were higher in inverted papilloma with atypia than in typical cases. In contrast, HPV-E4 and L1, which are markers for HPV propagation, were observed in some parts of the typical inverted papilloma tissue. High-risk HPV infection may be one of the causes of urothelial inverted papilloma, and inverted papilloma with atypia may have malignant potential.
Liquid-based urine cytology (LB-URC) was evaluated for cytological diagnosis and detection of human papillomavirus (HPV), Mycoplasma, and Ureaplasma. Midstream urine samples were collected from 141 male patients with urethritis and 154 controls without urethritis, and sediment cells were preserved in liquid-based cytology solution. Urethral swabs from urethritis patients were tested for the presence of Neisseria gonorrhoeae and Chlamydia trachomatis. Papanicolaou tests were performed for cytological evaluation. HPV, Mycoplasma, and Ureaplasma genomes were determined by PCR-based methods, and localization of HPV DNA in urothelial cells was examined by in situ hybridization (ISH). The -globin gene was positive in 97.9% of LB-URC samples from urethritis patients and in 97.4% of control samples, suggesting that high-quality cellular DNA was obtained from the LB-URC samples. HPV DNA was detected in 29 (21.0%) urethritis cases and in five (3.3%) controls (P < 0.05). HPV type 16 (HPV 16) was most commonly found in urethritis patients. Cytological evaluations could be performed for 92.1% of urethritis patients and 64.3% of controls. Morphological changes suggestive of HPV infection were seen in 20.7% of the HPV-positive samples, and ISH demonstrated the presence of HPV DNA in both squamous and urothelial cells in HPV-positive samples. Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma parvum, and Ureaplasma urealyticum were detected in 14.5%, 10.9%, 6.5%, and 12.3% of urethritis patients, respectively. The prevalence rates of these microorganisms (except Ureaplasma parvum) were significantly higher in urethritis cases than controls (P < 0.05). LB-URC is applicable for detection of HPV, Mycoplasma, and Ureaplasma. HPV infection occurs in urothelial cells, especially in gonococcal urethritis. Human papillomavirus (HPV) infection is known to cause uterine cervical cancer and precancerous lesions in women (14,29). HPV infection usually occurs through sexual intercourse, and it has been reported that the prevalence of HPV infection in sexually active healthy young women ranges from 20% to 60% (12,19,26). Thus, cervical HPV infection is thought to be one of the most common sexually transmitted infections (STIs) in women.Prophylactic HPV vaccine has become available worldwide to prevent cervical cancer, and the prevalence and sites of HPV infection in the male genital tract have been studied. Some studies indicated that the external male genitalia, including the penile shaft, glans, coronal sulcus, and prepuce, are the most common sites of HPV infection and that the prevalence of HPV among healthy young men is as high as that among healthy young women (9, 10). However, a systematic review indicated that the HPV detection rate in urine was less than 7% and that urine is unsuitable for HPV detection in epidemiological studies (9). Indeed, Giuliano et al examined the presence of HPV DNA in multiple genital sites of 186 healthy men and reported that HPV was detected most commonly on the penile shaft (49.9%), followed by the gl...
The critical factors and etiological role of human papillomavirus (HPV) infection in the development of female bladder tumor were examined. Eighty-four female patients with primary bladder tumor were studied. After DNA extraction from each paraffin-embedded tissue, HPV-DNA and genotype were checked. In cases of all HPV-positive cases and some HPV-negative cases, in situ hybridization (ISH) for high-risk HPV-DNA, and immunohistochemical analysis for p16-INK4a were performed. HPV-DNA was detected in 5 (6.0%) of 84 eligible patients, and HPV16 was detected in 3 patients, and HPV6 and HPV52 was detected in one case, respectively. HPV-DNA was detected frequently in younger patients and in patients with a history of cervical cancer. In four high-risk HPV-positive cases, high-risk HPV-DNA was present in tumor tissues, and p16-INK4a was expressed moderately or strongly. Two cases had a past history of cervical cancer. In these 2 cases, the same HPV type (HPV16) was detected from bladder tumor and cervical cancer. High-risk HPV-DNA ISH signals and p16-INK4A expression were also detected widely in these cervical cancer tissues. HPV infection is likely to play an important role in the development of female bladder tumor at younger cases with a past history of cervical cancer.
Objective To analyze perioperative blood pressure in patients undergoing transurethral resection of bladder tumor with photodynamic diagnosis. Methods A total of 109 consecutive patients who underwent photodynamic diagnosis‐assisted transurethral resection of bladder tumor at Kanazawa University, Kanazawa, Ishikawa, Japan, were included in this study and considered as the photodynamic diagnosis group. Clinical data were collected, and perioperative systolic bladder pressure and vasopressor usage were analyzed. In contrast, consecutive patients who previously underwent conventional transurethral resection of bladder tumor (without the use of oral 5‐aminolevulinic acid) were used as the control group. Results The systolic blood pressure before anesthesia, lowest systolic blood pressure from the anesthesia induction to the start of operation and lowest systolic blood pressure during operation were significantly lower in the photodynamic diagnosis group. The rate of vasopressor use was significantly higher in the photodynamic diagnosis group. On multivariate analysis, we found that general anesthesia and regular use of renin–angiotensin system inhibitor were associated with an increased risk of hypotension (lowest systolic blood pressure from the anesthesia induction to the start of operation <80 mmHg). Conclusions Oral intake of 5‐aminolevulinic acid can obviously cause a drop in intraoperative blood pressure in patients undergoing transurethral resection of bladder tumor. Therefore, urologists and anesthesiologists should consider withdrawal of renin–angiotensin system inhibitors and monitor the blood pressure during photodynamic diagnosis‐assisted transurethral resection of bladder tumor.
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