Comparison of PDD-TURBT alone versus white light TURBT plus intravesical BCG therapy: A propensity-score matching study.

BACKGROUND: Although photodynamic-diagnosed transurethral resection of bladder cancer (PDD-TURBT) and Bacillus Calmette-Guérin (BCG) intravesical instillation are the two representative therapies for non-muscle invasive bladder cancer (NMIBC), no studies directly compare their efficacy. We evaluated the outcome of PDD-TURBT alone compared with white light TURBT with intravesical BCG therapy and analyzed the efficacy of both therapies depending on the characteristics of the tumors. METHODS: We retrospectively analyzed intermediate- and high-risk NMIBC patients treated with PDD-TURBT alone (the PDD group) or white light TURBT with BCG therapy (the white light group) using propensity score matched analysis. RESULTS: In the propensity score matched cohort, the 1-, 2-, and 3-year recurrence-free survival rates for the PDD group were 77.6 %, 64.1 %, and 48.1 %, respectively, compared to 84.6 %, 75.1 %, and 75.1 % for the white light group (p = 0.44, 0.27, 0.17, respectively). The difference in recurrence rates between the two groups tended to become more pronounced over time, although there was no significant difference. In the univariate and multivariate analysis, recurrence, multiplicity, and tumor grade were the significant prognostic factors of recurrence in the PDD group (p = 0.010, 0.047, 0.048, respectively). Long-term RFS was similar in the PDD and white light groups when the population was limited to the primary and single tumors, suggesting that PDD-TURBT alone may be sufficient in this spectrum of patients. CONCLUSIONS: PDD-TURBT alone is insufficient to control the long-term recurrence of bladder cancer but can be effective in selected cases such as primary and single tumors.

Th1/17 polarization and potential treatment by an anti-interferon-γ DNA aptamer in Hunner-type interstitial cystitis.

Hunner-type interstitial cystitis (HIC) is a rare, enigmatic inflammatory disease of the urinary bladder with no curative treatments. In this study, we aimed to characterize the unique cellular and immunological factors specifically involved in HIC by comparing with cystitis induced by Mycobacterium bovis bacillus Calmette-Guérin, which presents similar clinicopathological features to HIC. Here, we show that T helper 1/17 +polarized immune responses accompanied by prominent overexpression of interferon (IFN)-γ, enhanced cGAS-STING cytosolic DNA sensing pathway, and increased plasma cell infiltration are the characteristic inflammatory features in HIC bladder. Further, we developed a mouse anti-IFN-γ DNA aptamer and observed that the intravesical instillation of the aptamer significantly ameliorated bladder inflammation, pelvic pain and voiding dysfunction in a recently developed murine HIC model with little migration into the blood. Our study provides the plausible basis for the clinical translation of the anti-IFN-γ DNA aptamer in the treatment of human HIC.

Enfortumab vedotin versus platinum rechallenge in post-platinum, post-pembrolizumab advanced urothelial carcinoma: A multicenter propensity score-matched study.

OBJECTIVE: Enfortumab vedotin (EV) was approved for advanced urothelial carcinoma (UC) in 2021 after the EV-301 trial showed its superiority to non-platinum-based chemotherapy as later-line treatment after platinum-based chemotherapy and immune checkpoint inhibitors including pembrolizumab. However, no study has compared EV with rechallenging platinum-based chemotherapy (i.e., "platinum rechallenge") in that setting. METHODS: In total, 283 patients received pembrolizumab for advanced UC after platinum-based chemotherapy between 2018 and 2023. Of them, 41 and 25 patients received EV and platinum rechallenge, respectively, as later-line treatment after pembrolizumab. After excluding two patients with EV without imaging evaluation, we compared oncological outcomes, including progression-free survival (PFS) and overall survival (OS), between the EV (n = 39) and platinum rechallenge groups (n = 25) using propensity score matching (PSM). RESULTS: Analyses on crude data (n = 64) showed no significant differences between the two groups regarding patients' baseline characteristics. PFS (5 months) and OS (11 months) in the EV group were comparable to those (8 and 12 months, respectively) in the platinum rechallenge group. After PSM (n = 36), the baseline characteristics between the two groups became more balanced, and PFS (not reached) and OS (not reached) in the EV group were comparable to those (8 and 11 months, respectively) in the platinum rechallenge group. CONCLUSIONS: EV and platinum rechallenge showed equivalent oncological outcomes, even after PSM, and both treatments should therefore be effective treatment options for post-platinum, post-pembrolizumab advanced UC.

Surgical resection in patient with teratoma with somatic-type malignancy transformed into rhabdomyosarcoma resulted in long-term survival.

Introduction: Testicular germ cell tumors with somatic-type malignancy, wherein teratomas transform into sarcomas, is drug resistant and has a poor prognosis. Case presentation: A 43-year-old man presented with a left testicular tumor, multiple pulmonary metastases, and mediastinal and para-aortic lymph node metastases. The testicular tumors were diagnosed as germ cell tumors. After bleomycin, etoposide, and cisplatin chemotherapy; right upper lobectomy for the pulmonary metastasis; and paclitaxel, ifosfamide, and cisplatin chemotherapy, rapidly progressing mediastinal lymph node metastasis was observed. It was resected at another specialized center owing to the challenging surgical approach. The histopathological diagnosis of the resected tumor was a teratoma with somatic-type malignancy (rhabdomyosarcoma). Subsequently, left hilar lymph node metastasectomy and left upper lobectomy were performed for the pulmonary metastases. The patient survived for more than 8 years after initial treatment. Conclusion: Surgery, although challenging, may yield long-term survival for patients with testicular germ cell tumors with sarcomatous transformation.

Increasing age predicts adverse pathology including intraductal carcinoma of the prostate and cribriform patterns in deferred radical prostatectomy after upfront active surveillance for Gleason grade group 1 prostate cancer: analysis of prospective observational study cohort.

BACKGROUND: In men undergoing upfront active surveillance, predictors of adverse pathology in radical prostatectomy specimens, including intraductal carcinoma of the prostate and cribriform patterns, remain unknown. Therefore, we aimed to examine whether adverse pathology in radical prostatectomy specimens could be predicted using preoperative patient characteristics. METHODS: We re-reviewed available radical prostatectomy specimens from 1035 men prospectively enrolled in the PRIAS-JAPAN cohort between January 2010 and September 2020. We defined adverse pathology on radical prostatectomy specimens as Gleason grade group ≥3, pT stage ≥3, pN positivity or the presence of intraductal carcinoma of the prostate or cribriform patterns. We also examined the predictive factors associated with adverse pathology. RESULTS: All men analyzed had Gleason grade group 1 specimens at active surveillance enrolment. The incidence of adverse pathologies was 48.9% (with intraductal carcinoma of the prostate or cribriform patterns, 33.6%; without them, 15.3%). The addition of intraductal carcinoma of the prostate or cribriform patterns to the definition of adverse pathology increased the incidence by 10.9%. Patients showing adverse pathology with intraductal carcinoma of the prostate or cribriform patterns had lower biochemical recurrence-free survival (log-rank P = 0.0166). Increasing age at active surveillance enrolment and before radical prostatectomy was the only predictive factor for adverse pathology (odds ratio: 1.1, 95% confidence interval: 1.02-1.19, P = 0.0178; odds ratio: 1.12, 95% confidence interval: 1.02-1.22, P = 0.0126). CONCLUSIONS: Increasing age could be a predictive factor for adverse pathology. Our findings suggest that older men could potentially derive advantages from adhering to the examination schedule in active surveillance.

Validation of a drug-based score in advanced urothelial carcinoma treated with pembrolizumab.

Aim: To validate a 'drug score' that stratifies patients receiving immunotherapy based on concomitant medications (antibiotics/proton pump inhibitors/corticosteroids) in urothelial carcinoma (UC). Materials & methods: We assessed oncological outcomes according to the drug score in 242 patients with advanced UC treated with pembrolizumab. Results: The drug score classified patients into three risk groups with significantly different survivals. Heterogeneous treatment effect analyses showed that the primary cancer site (bladder UC [BUC] or upper-tract UC [UTUC]) significantly affected the prognostic capability of the drug score; it significantly correlated with survivals in BUC, while there were no such correlations in UTUC. Conclusion: A drug score was examined in advanced UC treated with pembrolizumab and was validated in BUC but not in UTUC.

Drug treatment for cancer may be weakened by other drugs. We checked whether some kinds of drugs really weakened the effect of drug treatment for cancer. We found that it was true for some kinds of cancer but not for other kinds.

Comparison of Mirabegron and Vibegron in Women With Treatment-Naive Overactive Bladder: A Randomized Controlled Study.

OBJECTIVE: To compare the efficacy and safety of mirabegron versus vibegron in postmenopausal women with treatment-naïve overactive bladder (OAB). METHODS: We conducted a prospective randomized controlled study of women with treatment-naïve OAB. The patients received mirabegron or vibegron at 50 mg daily for 12 weeks by a stratified randomized method. The OAB symptom score (OABSS) and quality of life (QOL) index were evaluated before and 4 and 12 weeks after the treatment. The patients' 3-day voiding diary and postvoided residual urine volumes were evaluated before and 12 weeks after the treatment. RESULTS: Of 213 patients initially enrolled in this study, 199 patients were randomized to the mirabegron group (n = 97) or vibegron group (n = 102). Twelve weeks after the treatment, OABSS, QOL index, the numbers of micturition, urgency episodes, incontinence episodes, and voided volume per 24 hours were significantly improved compared with the baseline in both groups, and there was no significant difference in the rate of change in both groups. The postvoid residual urine volume was not significantly different in the 2 groups at 12 weeks. Discontinuation because of adverse effects was observed in 6.2% of patients in the mirabegron group and 6.8% in the vibegron group, with no significant difference between 2 groups. CONCLUSION: Both mirabegron at 50 mg and vibegron at 50 mg improved OAB symptoms and the parameters of voiding diary equally in postmenopausal women with treatment naïve OAB.

Subclassification of pT3 upper tract urothelial carcinoma: a multicenter retrospective study.

PURPOSE: The prognosis of patients with pT3 upper tract urothelial carcinoma (UTUC) varies. The current study aimed to further classify patients with pT3 UTUC into different survival outcome groups based on tumor location and site of invasion. METHODS: This retrospective study included 323 patients with pT3 UTUC who underwent nephroureterectomy at 11 hospitals in Japan. Histological and clinical data were obtained via a chart review. Univariate and multivariate Cox proportional hazards analyses showed the effect of different variables on recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: The median age of the patients was 72 years. Patients with pT3 UTUCs were divided into two groups: those with renal parenchymal invasion only (pT3a, n = 95) and those with peripelvic or periureteral fat invasion (pT3b, n = 228). pT3b UTUC was significantly associated with hydronephrosis, low preoperative estimated glomerular filtration rate (eGFR), histological nodal metastasis, nuclear grade 3, lymphovascular invasion (LVI), carcinoma in situ, and positive surgical margin. Based on the univariate analyses, patients with pT3b UTUC had a significantly lower 5-year RFS (42.4% vs. 70.1%, p < 0.0001), 5-year CSS (54.3% vs. 80.0%, p = 0.0002), and 5-year OS (47.8% vs. 76.8%, p < 0.0001) than those with pT3a UTUC. According to the multivariate analyses, nodal metastasis, LVI, adjuvant chemotherapy, preoperative eGFR, nuclear grade (RFS only), surgical margin (RFS only), and Charlson comorbidity index (OS only), but not pT3b stage, were associated with survival. CONCLUSION: Compared with pT3a UTUC, pT3b UTUC was significantly associated with worse histological features, consequently resulting in unsatisfactory survival outcomes.

Clinical outcomes of intraductal carcinoma or cribriform in radical prostatectomy specimens of men opting for active surveillance: data from the PRIAS-JAPAN study.

BACKGROUND: Among early stage prostate cancer patients, intraductal carcinoma of the prostate (IDC-P) and invasive cribriform are key prognostic factors; however, their presence and clinical significance following active surveillance (AS) are unknown. In men who opted for AS, we aimed to examine the presence and impact of IDC-P or cribriform, utilizing radical prostatectomy (RP) specimens. METHODS: We re-reviewed 137 RP specimens available in the PRIAS-JAPAN prospective cohort between January 2010 and September 2020. We assessed the presence of IDC-P or cribriform, and compared the patients' characteristics and prostate-specific antigen (PSA) recurrence-free survival after RP between groups with and without IDC-P or cribriform. In addition, we examined the predictive factors associated with IDC-P or cribriform. RESULTS: The percentage of patients with IDC-P or cribriform presence was 34.3% (47 patients). IDC-P or cribriform pattern was more abundant in the higher Gleason grade group in RP specimens (P < 0.001). The rates of PSA recurrence-free survival were significantly lower in the IDC-P or cribriform groups than in those without them (log rank P = 0.0211). There was no association between IDC-P or cribriform on RP with the Prostate Imaging-Reporting and Data System (PI-RADS) 4,5 score on magnetic resonance imaging (MRI) before RP even with adjustments for other covariates (OR, 1.43; 95% confidence interval [CI] 0.511-3.980, P = 0.497). CONCLUSIONS: IDC-P or cribriform comprised approximately one-third of all RP specimens in men who underwent RP following AS, confirming their prognostic significance.

Comparison of full-dose gemcitabine/cisplatin, dose-reduced gemcitabine/cisplatin, and gemcitabine/carboplatin in real-world patients with advanced urothelial carcinoma.

BACKGROUND: While gemcitabine/cisplatin (GC) is the gold standard regimen for patients with advanced urothelial carcinoma (aUC), either dose-reduced GC or gemcitabine/carboplatin (GCa) is an alternative option for "cisplatin-unfit" patients. However, few studies have compared outcomes with these commonly used regimens in the real-world setting. METHODS: We retrospectively reviewed patients with aUC who received full-dose GC, dose-reduced GC, or GCa as first-line salvage chemotherapy at two university hospitals between 2016 and 2020. Progression-free survival, cancer-specific survival, and overall survival, as well as best overall response and adverse event profiles, were compared among these three regimens. RESULTS: Of 105 patients, 41, 27, and 37 patients received full-dose GC, dose-reduced GC, and GCa, respectively. Significant differences were noted in the patients' baseline age, primary site, and renal function among the three regimens. Sixty-nine (65.7%) patients died during a median follow-up period of 14 months. There was no significant difference among the three regimens for all survival outcomes and best overall response. However, the complete response rate of dose-reduced GC (2/27, 7.4%) appeared inferior to that of full-dose GC (9/41, 22.0%) or GCa (6/37, 16.2%). Regarding adverse event profiles, no significant difference was observed among the three regimens, except for significantly fewer cases with elevated alanine aminotransferase in the GCa group compared with the other groups. CONCLUSIONS: This study compared the oncological and toxicological outcomes of full-dose GC, dose-reduced GC, and GCa in real-world patients with aUC. Unlike in the clinical trial setting, there were almost no significant differences among the three regimens.

The association between the parameters of uroflowmetry and lower urinary tract symptoms in prostate cancer patients after robot-assisted radical prostatectomy.

OBJECTIVE: To investigate changes in uroflowmetry parameters in men undergoing robot-assisted radical prostatectomy (RARP) for prostate cancer. MATERIALS AND METHODS: Four hundred and twenty-eight patients received uroflowmetry testing before and after RARP from November 2011 to December 2018. Clinicopathological data, including age, initial prostate-specific antigen (PSA), prostate volume, clinical stage, body mass index (BMI), uroflowmetry parameters, and core lower urinary tract symptom scores (CLSS) were retrospectively obtained from clinical records. Changes in uroflowmetry parameters were analyzed for statistical predictors and effects on post-operative outcomes. RESULTS: A significant increase in maximum flow rate (MFR) and decreases in voided volume (VV) and post-void residual urine (PVR) were seen. In multivariate analysis, age was a negative predictor of MFR increase, while prostate volume was a positive predictor of PVR decrease and MFR increase. VV decrease led to worse incontinence symptoms, while PVR decrease and MFR increase led to improvement in voiding symptoms such as slow stream and straining. Continence recovery curves showed that VV decrease were associated with a delay in continence recovery. CONCLUSIONS: Significant changes were seen in uroflowmetry results after RARP, each parameter directly related to urinary symptoms. In particular, VV decrease was associated with a worsening of incontinence symptoms and continence recovery.

Improved survival in real-world patients with advanced urothelial carcinoma: A multicenter propensity score-matched cohort study comparing a period before the introduction of pembrolizumab (2003-2011) and a more recent period (2016-2020).

OBJECTIVES: Although the treatment strategy for advanced urothelial carcinoma (aUC) has drastically changed since pembrolizumab was introduced in 2017, studies revealing current survival rates in aUC are lacking. This study aimed to assess (1) the improvement in survival among real-world patients with aUC after the introduction of pembrolizumab and (2) the direct survival-prolonging effect of pembrolizumab. METHODS: This multicenter retrospective study included 531 patients with aUC undergoing salvage chemotherapy, including 200 patients treated in the pre-pembrolizumab era (2003-2011; earlier era) and 331 patients treated in a recent 5-year period (2016-2020; recent era). Using propensity score matching (PSM), cancer-specific survival (CSS) and overall survival (OS) were compared between the earlier and recent eras, in addition to between the recent era, both with and without pembrolizumab use, and the earlier era. RESULTS: After PSM, the recent era cohort had significantly longer CSS (21 months) and OS (19 months) than the earlier era cohort (CSS and OS: 12 months). In secondary analyses using PSM, patients treated with pembrolizumab had significantly longer CSS (25 months) and OS (24 months) than those in the earlier era cohort (CSS and OS: 11 months), whereas patients who did not receive pembrolizumab in the recent era had similar outcomes (CSS and OS: 14 months) as the earlier era cohort (CSS and OS: 12 months). CONCLUSIONS: Patients with aUC treated in the recent era exhibited significantly longer survival than those treated before the introduction of pembrolizumab. The improved survival was primarily attributable to the use of pembrolizumab.

The 'prostate-muscle index': a simple pelvic cavity measurement predicting estimated blood loss and console time in robot-assisted radical prostatectomy.

This study was to show the impact of 'prostate-muscle index (PMI)', which we developed as a novel pelvic cavity measurement, in patients undergoing robot-assisted radical prostatectomy (RARP). We defined PMI as the 'distance between the inner edge of the obturator internus muscle and the lateral edge of the prostate at the magnetic resonance imaging (MRI) slice showing the maximum width of the prostate'. Seven hundred sixty patients underwent RARP at the University of Tokyo Hospital from November 2011 to December 2018. MRI results were unavailable in 111 patients. In total, 649 patients were eligible for this study. Median values of blood loss and console time were 300 mL and 168 min. In multivariate analysis, body mass index (BMI), prostate volume-to-pelvic cavity index (PV-to-PCI), PMI, and surgical experience were significantly associated with blood loss > 300 mL (P = 0.0002, 0.002, < 0.0001, and 0.006 respectively). Additionally, BMI, PMI, and surgical experience were also significantly associated with console time > 160 min in multivariate analysis (P = 0.04, 0.004, and < 0.0001, respectively). In conclusion, PMI may provide useful information to surgeons and patients in preoperative decision-making.

Comparison of the medical costs between active surveillance and other treatments for early prostate cancer in Japan using data from the PRIAS-JAPAN study.

OBJECTIVES: To compare the medical costs of active surveillance with those of robot-assisted laparoscopic prostatectomy, brachytherapy, intensity-modulated radiation therapy, and hormone therapy for low-risk prostate cancer. METHODS: The costs of protocol biopsies performed in the first year of surveillance (between January 2010 and June 2020) and those of brachytherapy and radiation therapy performed between May 2019 and June 2020 at the Kagawa University Hospital were analyzed. Hormone therapy costs were assumed to be the costs of luteinizing hormone-releasing hormone analogs for over 5 years. Active surveillance-eligible patients were defined based on the following: age <74 years, ≤T2, Gleason score ≤6, prostate-specific antigen level ≤10 ng/ml, and 1-2 positive cores. We estimated the total number of active surveillance-eligible patients in Japan based on the Japan Study Group of Prostate Cancer (J-CAP) study and the 2017 cancer statistical data. We then calculated the 5-year treatment costs of active surveillance-eligible patients using the J-CAP and PRIAS-JAPAN study data. RESULTS: In 2017, number of active surveillance-eligible patients in Japan was estimated to be 2808. The 5-year total costs of surveillance, prostatectomy, brachytherapy, radiation therapy, and hormone therapy were 1.65, 14.0, 4.61, 4.04, and 5.87 million United States dollar (USD), respectively. If 50% and 100% of the patients in each treatment group had opted for active surveillance as the initial treatment, the total treatment cost would have been reduced by USD 6.89 million (JPY 889 million) and USD 13.8 million (JPY 1.78 billion), respectively. CONCLUSION: Expanding active surveillance to eligible patients with prostate cancer helps save medical costs.

Impact of adherence to criteria on oncological outcomes of radical prostatectomy in patients opting for active surveillance: data from the PRIAS-JAPAN study.

OBJECTIVES: This study aimed to evaluate whether oncological outcomes of radical prostatectomy differ depending on adherence to the criteria in patients who opt for active surveillance. MATERIALS AND METHODS: We retrospectively reviewed the data of 1035 patients enrolled in a prospective cohort of the PRIAS-JAPAN study. After applying the exclusion criteria, 136 of 162 patients were analyzed. Triggers for radical prostatectomy due to pathological reclassification on repeat biopsy were defined as on-criteria. Off-criteria triggers were defined as those other than on-criteria triggers. Unfavorable pathology on radical prostatectomy was defined as pathological ≥T3, ≥GS 4 + 3 and pathological N positivity. We compared the pathological findings on radical prostatectomy and prostate-specific antigen recurrence-free survival between the two groups. The off-criteria group included 35 patients (25.7%), half of whom received radical prostatectomy within 35 months. RESULTS: There were significant differences in median prostate-specific antigen before radical prostatectomy between the on-criteria and off-criteria groups (6.1 vs. 8.3 ng/ml, P = 0.007). The percentage of unfavorable pathologies on radical prostatectomy was lower in the off-criteria group than that in the on-criteria group (40.6 vs. 31.4%); however, the differences were not statistically significant (P = 0.421). No significant difference in prostate-specific antigen recurrence-free survival was observed between the groups during the postoperative follow-up period (median: 36 months) (log-rank P = 0.828). CONCLUSIONS: Half of the off-criteria patients underwent radical prostatectomy within 3 years of beginning active surveillance, and their pathological findings were not worse than those of the on-criteria patients.

Principal component analysis of early immune cell dynamics during pembrolizumab treatment of advanced urothelial carcinoma.

Immune checkpoint inhibitors have been approved as second-line therapy for patients with advanced urothelial carcinoma (UC). However, which patients will obtain clinical benefit remains to be determined. To identify predictive biomarkers for the pembrolizumab (PEM) response early during treatment, the present study investigated 31 patients with chemotherapy-resistant recurrent or metastatic UC who received 200 mg PEM intravenously every 3 weeks. Blood was taken just before the first dose and again before the second dose, and the peripheral blood mononuclear cells of all 31 pairs of blood samples were immune phenotyped by flow cytometry. Data were assessed by principal component analysis (PCA), correlation analysis and Cox proportional hazards modeling in order to comprehensively determine the effects of PEM on peripheral mononuclear immune cells. Absolute counts of CD45RA+CD27-CCR7- terminally differentiated CD8+ T cells and KLRG1+CD57+ senescent CD8+ T cells were significantly increased after PEM administration (P=0.042 and P=0.043, respectively). Senescent and exhausted CD4+ and CD8+ T cell dynamics were strongly associated with each other. By contrast, counts of monocytic myeloid-derived suppressor cells (mMDSCs) were not associated with other immune cell phenotypes. The results of PCA and non-hierarchical clustering of patients suggested that excessive T cell senescence and differentiation early during treatment were not necessarily associated with a survival benefit. However, decreased mMDSC counts after PEM were associated with improved overall survival. In conclusion, early on-treatment peripheral T cell status was associated with response to PEM; however, it was not associated with clinical benefit. By contrast, decreased peripheral mMDSC counts did predict improved overall survival.

A case of miliary tuberculosis following transurethral surgery and prostate biopsy after intravesical Bacillus Calmette-Guerin immunotherapy.

INTRODUCTION: Intravesical Bacillus Calmette-Guerin immunotherapy is known to prevent recurrence of bladder cancer, but it can cause tuberculosis infections as an adverse event. CASE PRESENTATION: A 75-year-old man visited our hospital due to hematuria. The patient was diagnosed with bladder cancer and underwent transurethral resection of the bladder tumor. Postoperatively, the patient received Bacillus Calmette-Guerin immunotherapy. One year later, we performed transurethral surgery and prostate biopsy because of cystoscopic findings showing nodulous lesions in the bladder and an elevated serum prostate-specific antigen level. The patient presented with high fever and malaise since the surgery. After careful examination, the patient was diagnosed with miliary tuberculosis caused by Mycobacterium bovis. The pathology of the bladder and prostate revealed acid-fast bacilli collection by Ziehl-Neelsen staining. CONCLUSION: The surgery exacerbated the local infection into a systemic infection. The risk of developing miliary tuberculosis should be considered at transurethral surgery or prostate biopsy in patients after intravesical Bacillus Calmette-Guerin immunotherapy.

[AUTOTRANSPLANTATION FOR IATROGENIC URETERAL INJURY FOLLOWING GYNECOLOGICAL SURGERY].

A 48-year-old woman underwent total hysterectomy and oophorectomy for uterine fibroids and bilateral ovarian cysts. Postoperatively, her renal function worsened, and the histological specimen contained ureteral tissue. She was referred to our department for left ureteral injury repair. An anterograde pyelogram revealed a ureteral defect, 9.5 cm in size. We considered ureteral bladder anastomosis to be complicated. She underwent kidney autotransplantation into her right iliac fossa to repair the ureteral injury. Six months after the operation, renal function was preserved, no hydronephrosis was observed by ultrasonography, and renal blood flow was good. Based on the literature on the difficulty of reconstructing ureteral injury, we developed an algorithm based on the length of ureteral injury.

Overexpression of HIF1α in Hunner Lesions of Interstitial Cystitis: Pathophysiological Implications.

PURPOSE: The aim of our study was to elucidate biological changes in Hunner lesions, which underlie the pathophysiology of Hunner-type interstitial cystitis, by characterizing their whole transcriptome and immunopathological profiles. MATERIALS AND METHODS: Paired bladder mucosal biopsies, 1 sample each from the Hunner lesion and nonlesion area, were obtained from 25 patients with Hunner-type interstitial cystitis. The samples were subjected to whole-transcriptome profiling; immunohistochemical quantification of CD3, CD4, CD8, CD20, CD138, mast cell tryptase, cytokeratin and HIF1α; and quantitative polymerase chain reaction for IFN-α, IFN-ß, IFN-γ, TNF, TGF-ß1, HIF1α, IL-2, IL-4, IL-6, IL-10 and IL-12A. The results were compared between the lesion and nonlesion areas. RESULTS: RNA sequencing identified 109 differentially expressed genes and 30 significantly enriched biological pathways in Hunner lesions. Up-regulated pathways (24) included HIF1α signaling pathway, PI3K-Akt signaling pathway, RAS signaling pathway and MAPK signaling pathway. By contrast, down-regulated pathways (6) included basal cell carcinoma and protein digestion and absorption. The mRNA levels of HIF1α, IFN-γ and IL-2, and the HIF1α protein level were significantly higher in lesion areas. Otherwise, there were no significant differences between the lesion and nonlesion samples in terms of mRNA levels of inflammatory cytokines or histological features such as lymphoplasmacytic and mast cell infiltration, epithelial denudation and CD4/CD8 T-lymphocyte ratio. CONCLUSIONS: Our findings demonstrate significant overexpression of HIF1α and up-regulation of its related biological pathways in Hunner lesions. The results indicate that ischemia, in conjunction with inflammation, plays a pathophysiological role in this subtype of interstitial cystitis/bladder pain syndrome, particularly in Hunner lesions.