Are bladder washing samples suitable for investigation of HPV infection in urinary bladder? Comparison in HPV prevalence between urine and washing samples.

Although urine and bladder washing samples are commonly used for the cytological evaluation of the bladder mucosa, it has been unknown whether these samples are likely suitable to investigate human papillomavirus (HPV) prevalence in the urinary bladder. The present study aimed to elucidate the appropriateness of spontaneously voided urine or bladder washing in screening HPV infection in the urinary bladder. Urine and bladder washing samples were obtained from 201 patients who underwent transurethral bladder tumor resection. After extracting DNA from both samples, HPV-DNA was examined using a nested polymerase chain reaction with GP5+/6+ and MY09/11 primers. HPV genotyping was performed in the HPV-positive samples. In situ hybridization (ISH) was performed to observe the HPV-DNA localization in urothelial cells among cytological samples and paraffin-embedded tumor tissues in HPV-positive washing samples. HPV prevalence in urine and washing samples were 9.5% and 7.0%, respectively. High-risk HPV prevalence in urine and washing samples was 7.5% and 4.0%, respectively. The most common HPV type was HPV 16, followed by HPV 52 and HPV 18 in both samples. HPV type distribution in both samples was not in agreement (κ = -0.431). The ISH analysis revealed that HPV-DNA signal was observed in urothelial cells of five (55.7%) of nine detectable HPV-positive cytological samples. Six (66.7%) of nine HPV-positive cases had HPV-DNA signals in tumor tissue. The use of washing samples was likely applicable for investigating HPV prevalence in the urinary bladder. HPV-DNA detected in washing samples might be frequently derived from the urinary bladder.

Variations in photodynamic diagnosis for bladder cancer due to the quality of endoscopic equipment.

BACKGROUND: Photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumor (TURBT) has different treatment outcomes across institutions, as seen in conventional TURBT. We retrospectively compared the difference in quality between the two types of endoscopic equipment used for PDD-assisted TURBT in our institution. METHODS: This study enrolled 205 consecutive patients who underwent PDD-assisted TURBT. Patients were divided into two groups according to the endoscopic equipment used for PDD-assisted TURBT: Group A using the conventionally used endoscopic system and Aladuck LS-DLED and Group S using the Storz PDD system. Cystoscopy findings of white light (WL), fluorescence light (FL), and combination (positive if either WL or FL was positive) were recorded, and diagnostic quality of PDD was compared between both groups. RESULTS: Group A had 105 cases and 336 specimens, while Group S had 100 cases and 361 specimens, with no significant differences between patient characteristics. The tumor sensitivities of WL, FL, and combination in Group A was 71.9%, 77.1%, 90.5%, respectively, while in Group S, these were 71.5%, 92.2%, 96.1%, respectively. Group S had significantly higher sensitivity of FL and combination than Group A, as well as higher detection of carcinoma in situ lesions. CONCLUSION: Both endoscopic systems had improved sensitivity with PDD-assistance versus WL only, with Group S having higher sensitivity. Differences in the quality of endoscopic equipment may influence the differences in treatment results with PDD-assisted TURBT across institutions.

Three-dimensional morphological analysis of spermatogenesis in aged mouse testes.

Spermatogenesis, which is a continuous process from undifferentiated spermatogonia to spermatozoa in the seminiferous tubules, declines with age. To investigate changes in spermatogenesis with aging, we reconstructed the seminiferous tubules of 12 mice aged 12 to 30 months from serial sections and examined age-related and region-specific alterations in the seminiferous epithelium and spermatogenic waves in three dimensions. The basic structure of the seminiferous tubules, including the numbers of tubules, terminating points, branching points, and total tubule length, did not change with age. Age-related alterations in spermatogenesis, primarily assessed by the formation of vacuoles in Sertoli cells, were detected in the seminiferous tubules at 12 months. The proportion of altered tubule segments with impaired spermatogenesis further increased by 24 months, but remained unchanged thereafter. Altered tubule segments were preferentially distributed in tubule areas close to the rete testis and those in the center of the testis. Spermatogenic waves became shorter in length with age. These results provide a basis for examining the decline of spermatogenesis not only with aging, but also in male infertility.

Anti-proliferative and anti-migratory properties of coffee diterpenes kahweol acetate and cafestol in human renal cancer cells.

Despite improvements in systemic therapy options for renal cancer, it remains one of the most drug-resistant malignancies. Interestingly, reports have shown that kahweol and cafestol, natural diterpenes extracted from coffee beans, exhibit anti-cancer activity. However, the multiple potential pharmacological actions of both have yet to be fully understood. This study therefore investigated the effects of kahweol acetate and cafestol on human renal cancer ACHN and Caki-1 cells. Accordingly, the combination of kahweol acetate and cafestol administration synergistically inhibited cell proliferation and migration by inducing apoptosis and inhibiting epithelial-mesenchymal transition. Mechanistic dissection revealed that kahweol acetate and cafestol inhibited Akt and ERK phosphorylation. Moreover, kahweol acetate and cafestol downregulated the expression of not only C-C chemokine receptors 2, 5, and 6 but also programmed death-ligand 1, indicating their effects on the tumor microenvironment. Thus, kahweol acetate and cafestol may be novel therapeutic candidates for renal cancer considering that they exert multiple pharmacological effects.

Therapeutic Effect of Ethinylestradiol in Castration-resistant Prostate Cancer.

BACKGROUND/AIM: The best sequential treatment for castration-resistant prostate cancer (CRPC) remains unclear. This study evaluated the therapeutic effects of ethinylestradiol (EE) on CRPC. PATIENTS AND METHODS: A total of 80 patients with CRPC, treated with 0.5-1.5 mg/day of EE, were retrospectively assessed. RESULTS: The median duration from the initial treatment to the beginning of EE was 48.3 months. A decline in the prostate-specific antigen (PSA) from the baseline was noted in 60 patients (75%) and a >50% PSA decline in 27 patients (34%). The median time of PSA progression, overall survival, and cancer-specific survival after EE were 5.60 months, 24.00 months, and 27.93 months, respectively. CONCLUSION: EE administration for CRPC showed a relatively high PSA response regardless of timing of sequential treatment. The frequency of cardiovascular adverse events was not significantly high. EE administration is a potential treatment option for CRPC.

Reply to Comment on "Kadomoto, S. et al. Tumor-Associated Macrophages Induce Migration of Renal Cell Carcinoma Cells via Activation of the CCL20-CCR6 Axis" Cancers 2020 12, 89.

We appreciate Zins and Abraham [1] commenting on our paper studying the role of the CCL20-CCR6 axis on renal cell carcinoma (RCC) cells [2]. As they pointed out, our study has certain limitations. Although M1- and M2-types cannot be separated clearly and a consecutive change of character might exist between them, it has been reported that plural specific markers express on M1- and M2-types. Unfortunately, a definite difference between M1 and M2 macrophages was not confirmed in our study. For more differentiation, multiple stimulations, such as suggested in the comments of Zins and Abraham, might be needed. Hence, we needed to expediently use "M1-like" and "M2-like" to mention specific status of these macrophage-like cells. Meanwhile, CCL20 expression levels of M2-like-THP-1 cells co-cultured with RCC cells were dramatically increased compared with parental THP-1 cells, indicating that certain stimulations within the tumor microenvironment rather than theoretical stimulations make macrophages differentiated; however, further studies are needed to clarify this mechanism using a more appropriate co-culture system mimicking the tumor microenvironment. Immunohistochemistry of CCL20 and M2 markers will help to better understand the role of tissue infiltrating macrophages, even tissue CD68 staining intensity itself was reported to correlate with prognosis of RCC patients [3]. [...].

Three-Dimensional Analysis of Busulfan-Induced Spermatogenesis Disorder in Mice.

We examined if the distribution of impaired or normal spermatogenesis differs along the length of seminiferous tubules in disorders of spermatogenesis. For this purpose, three-dimensional (3D) reconstruction of seminiferous tubules was performed in mice with experimental spermatogenesis disorder induced by intraperitoneal injection of busulfan, and the areas of impaired and normal spermatogenesis were analyzed microscopically. The volume of the testis and length of seminiferous tubules decreased, and the proportion of tubule areas with impaired spermatogenesis increased depending on the dose of busulfan. With the highest dose of busulfan, although the proportion of impaired spermatogenesis was similar among individual seminiferous tubules, it was slightly but significantly higher in shorter tubules and in tubule areas near branching points. The tubule areas with impaired and normal spermatogenesis consisted of many segments of varying lengths. With increasing doses of busulfan, the markedly impaired segments increased in length without changing in number, whereas normal segments, although reduced in number and length, remained even with the highest dose of busulfan. Individual remaining normal segments consisted of several different stages, among which stage I and XII were found at higher frequencies, and stage VI at a lower frequency than expected in normal seminiferous tubules. We also examined if the distribution of impaired or normal spermatogenesis differs among different 3D positions in the testis without considering the course of seminiferous tubules. Although the proportions of impaired spermatogenesis with the minimum dose of busulfan and normal spermatogenesis with the highest dose of busulfan greatly varied by location within a single testis, there were no 3D positions with these specific proportions common to different testes, suggesting that the factors influencing the severity of busulfan-induced spermatogenesis disorder are not fixed in location among individual mice.

Intraoperative hypotension caused by oral administration of 5-aminolevulinic acid for photodynamic diagnosis in patients with bladder 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.

Tumor-Associated Macrophages Induce Migration of Renal Cell Carcinoma Cells via Activation of the CCL20-CCR6 Axis.

This study investigated tumor-associated macrophages activity in the microenvironment of renal cell carcinoma. Via a co-culture with macrophage-like cells differentiated from human monocyte cell line THP-1 and U937 cells, the migration ability of ACHN and Caki-1 cells, which are human renal cell carcinoma cell line cells, was significantly increased, as was the epithelial-mesenchymal transition change. A chemokine array identified the CCL20-CCR6 axis as a concentration-dependent signal in ACHN and Caki-1 cell migration. Akt in the ACHN and Caki-1 cells was activated by macrophage-like cells, and the CCL20 neutralizing antibody suppressed migration ability, epithelial-mesenchymal transition, and Akt phosphorylation in the ACHN and Caki-1 cells. Akt inhibitor AZD5363 also decreased the epithelial-mesenchymal transition change and migration ability in the ACHN and Caki-1 cells. In 42 renal cell carcinoma tissues, patients with CCR6 and macrophage infiltration indicated poor prognoses. In the tumor microenvironment of renal cell carcinoma, cancer cells are activated by CCL20 secreted by tumor-associated macrophages through Akt activation, followed by epithelial-mesenchymal transition and an acquired migration ability. Thus, inhibition of the CCL20-CCR6 axis may be a potential therapeutic strategy for renal cell carcinoma.

Metanephric adenoma treated with laparoscopic nephrectomy: A case report.

Metanephric adenoma is an uncommon benign renal tumor that occurs predominantly in adult females and rarely in children. Its histomorphology resembles that of epithelial Wilms' tumor and papillary renal cell carcinoma. From a diagnostic and therapeutic perspective, recognition of this entity is important as it has a more favorable clinical outcome compared with Wilms' tumor and renal cell carcinoma. Metanephric adenoma should not be treated with nephrectomy if the tumor size is small. However, preoperative diagnosis of this disease is extremely challenging. The present study describes a case of this rare disease, which was treated with laparoscopic nephrectomy. The tumor was not clearly enhanced in the early phase on contrast-enhanced computed tomography imaging. The immunohistochemical analysis revealed positive immunoreactivity for vimentin and Wilms' tumor 1, and partial positivity for cytokeratin (CK) AE1/AE3, CK56, and CK34, consistent with metanephric adenoma. Although metanephric adenoma is difficult to diagnose preoperatively, this rare disease must be considered in order to avoid unnecessary surgical procedures in these patients.

Aplastic anemia associated with severe hemorrhagic cystitis following radiotherapy for prostate cancer.

Hemorrhagic cystitis is a rare complication following radiotherapy for intrapelvic cancer types, including cervical cancer, bladder cancer and prostate cancer. The severity of hemorrhagic cystitis is different in each case, although symptoms improve spontaneously in certain cases, and often significant morbidity requiring numerous interventions occurs. Since no treatment strategy exists with high evidences for such severe hemorrhagic cystitis, urologists have difficulty in solving the bleeding and pain, which the patients suffer. Aplastic anemia is a rare blood disorder, with an incidence reported as 2/1 million individuals annually. Patients have a risk of diffuse bleeding for presentation with anemia, thrombocytopenia and neutropenia. The present report presented a case of severe hemorrhagic cystitis remitted successfully by the treatment for underlying aplastic anemia.

Invasive urothelial carcinoma within a calyceal diverticulum associated with renal stones: A case report.

Calyceal diverticula are rare outpouchings of the upper collecting system lying within the renal parenchyma. These often contain stones, however, carcinoma within a calyceal diverticulum is uncommon. The present study reports a case of invasive urothelial carcinoma within a calyceal diverticulum associated with renal stones. A 70-year-old male with a left renal mass identified by abdominal computed tomography was referred to the Department of Urology, Kanazawa University Hospital. Pre-operative diagnosis was difficult owing to an atypical imaging finding of a hypovascular renal mass with calcification. A laparoscopic nephroureterectomy was performed, and the surgical specimens showed invasive high-grade urothelial carcinoma within a calyceal diverticulum, and the calcifications were renal stones consisting of 97% calcium oxalate. Urothelial carcinoma in calyceal diverticula is a rare condition, however, a pre-operative definite diagnosis is difficult and a high potential for invasion of the renal parenchyma is suspected in this disease.