Salvage Androgen Deprivation Therapy as Potential Treatment for Recurrence after Robot-Assisted Radical Prostatectomy.

BACKGROUND: The efficacy of intermittent androgen deprivation therapy (ADT) for biochemical recurrence (BCR) after robot-assisted radical prostatectomy (RARP) is unknown, and its usefulness in Japanese practice needs to be investigated. METHODS: We conducted a retrospective analysis of 85 patients who underwent RARP and were selected for intermittent ADT for postoperative recurrence at Kanazawa University Hospital between 2009 and 2019. Intermittent ADT was administered for 2 years. If prostate-specific antigen levels increased post-treatment, intermittent ADT was reinitiated. The median follow-up period was 47 months. RESULTS: The 73 patients had completed the initial course of ADT, and 12 were under initial ADT. The 5-year castration-resistant prostate-cancer-free survival rates, cancer-specific survival, and overall survival were 92.7%, 98.3%, and 94.7%, respectively. A subgroup analysis of 69 patients who completed intermittent ADT was conducted to evaluate the BCR rate following initial ADT. The 5-year BCR-free survival rate was 53.2%. Multivariate analysis identified testosterone ≤ 0.03 ng/mL during ADT as the sole predictor of BCR after ADT. CONCLUSIONS: Salvage intermittent ADT may be an effective treatment option for BCR after RARP. In addition, it would be useful to confirm strong testosterone suppression as a criterion for transition to intermittent therapy.

Enzalutamide versus Abiraterone Plus Prednisolone for Nonmetastatic Castration-Resistant Prostate Cancer: A Sub-Analysis from the ENABLE Study for PCa.

Enzalutamide (ENZ) and abiraterone plus prednisolone (ABI) can improve the survival of patients with castration-resistant prostate cancer (CRPC). However, the agent that is more effective against nonmetastatic CRPC remains unclear. To evaluate the agent that can be used as the first-line treatment for CRPC, an investigator-initiated, multicenter, randomized controlled trial (ENABLE Study for PCa) including both metastatic and nonmetastatic CRPC was conducted in Japan. The prostate-specific antigen (PSA) response rate, overall survival, some essential survival endpoints, and safety of patients with nonmetastatic CRPC were also analyzed. In this subanalysis, 15 and 26 patients in the ENZ and ABI arms, respectively, presented with nonmetastatic CRPC. There was no significant difference in terms of the PSA response rate between the ENZ and ABI arms (80% and 64%, respectively; p = 0.3048). The overall survival did not significantly differ between the two arms (HR: 0.68; 95% CI: 0.22-2.14, p = 0.5260). No significant differences were observed in terms of radiographic progression-free survival and cancer-specific survival between the ENZ and ABI arms (HR: 0.81; 95% CI: 0.35-1.84; p = 0.6056 and HR: 0.72; 95% CI: 0.19-2.73; p = 0.6443, respectively). Only four and six patients in the ENZ and ABI arms, respectively, had ≥grade 3 adverse events. ABI and ENZ had similar efficacy and safety profiles in patients with nonmetastatic CRPC.

Role of Positive Biopsy Core Ratio in Prostate Cancer Patients.

BACKGROUND/AIM: The percentage of positive cores (PPC) is increasingly recognized as a prognostic factor in prostate cancer. However, the usefulness of PPC for patients undergoing androgen deprivation therapy (ADT) and high-risk group has not been adequately studied. PATIENTS AND METHODS: A retrospective analysis was conducted of 255 patients who underwent prostate biopsy (all-case group). We examined the efficacy of PPC as a prognostic biomarker. RESULTS: Eighty-nine patients were treated with ADT alone (ADT group), and 107 patients were classified as high-risk (high-risk group). The median duration of follow-up was 112.4 months, 85.3 months, and 110.0 months for the all-case, ADT, and high-risk groups, respectively. Patients with PPC >60% had significantly shorter prostate cancer-specific survival (CSS) and castration-resistant prostate cancer-free survival (CFS) in the all-case and ADT groups. In the high-risk group, patients with PPC >60% had shorter CFS but no difference in CSS. Multivariate analysis showed that significant independent predictors of prostate CSS were the presence of metastasis at diagnosis and PPC >60% in the all-case and ADT groups. CONCLUSION: PPC may be a prognostic factor in ADT treated and high-risk prostate patients.

Efficacy of keishibukuryogan for hot flashes in prostate cancer patients receiving androgen deprivation therapy: a sub-analysis focusing on hormonal and cytokine levels.

Background: The current study attempted to elucidate the mechanisms of keishibukuryogan (TJ-25) efficacy by focusing on hormonal and cytokine levels. This is a sub-analysis of serum hormonal and cytokine levels extracted from the single-arm prospective study. Methods: Twenty-five participants were administrated TJ-25 at a dose of 2.5 g three times daily for 12 weeks, and competed for a diary of their hot flashes conditions. Various hormonal and cytokine values, including interleukin (IL)-8 and tumor necrosis factor-α (TNF-α), were measured at the baseline and 12-week visits. The correlation of hot flashes with hormonal and cytokine levels at baseline was investigated. As part of the responder analyses, all participants were divided into two groups based on the median baseline values of all hormones and cytokines at baseline, and the change amounts in strength and frequency of hot flashes from baseline to 12-week visits in both groups were compared. Furthermore, a correlation in change amounts (Δ values) by TJ-25 administration between hot flashes and each parameter was also conducted. Results: Hot flashes intensity was inversely related to estradiol levels (r=-0.433, P=0.019), and frequency was inversely related to progesterone levels (r=-0.415, P=0.025). In the responder analyses, the effectiveness of TJ-25 for hot flash strength increased in the patients with higher levels of TNF-α at baseline (P=0.0372). TJ-25 was more efficient in frequency in the patients with higher levels of IL-8 (P=0.0312). TJ-25 efficacy, on the other hand, was not significantly associated with changes in any hormonal or cytokine levels between the baseline and 12-week visits. However, ΔIL-8 and ΔTNF-α were not significantly correlated with Δstrength and Δfrequency of hot flashes by TJ-25 administration. Conclusions: Hot flashes were inversely correlated with estradiol and progesterone levels. TJ-25 was more effective in patients with higher TNF-α and IL-8 levels, with no significant change in serum levels caused by the treatment. The suggestive mechanism for the effects of keishibukuryogan is that this drug doesn't suppress the production of IL-8 and TNF-α, but may inhibit some actions of these cytokines.

Relation between athletic club affiliation from school age and future serum free testosterone levels in Japan: A cross-sectional study.

Background and Aims: Testosterone deficiency is often related to geriatric syndrome including erectile dysfunction, osteo-porosis, depression, cognitive impairment, cardiovascular diseases and frailty. Despite the existence of many studies on short-term exercise and serum testosterone levels, few research have focused on exercise habits from young age and testosterone values in middle-aged male. In this study, we investigated whether belonging to an athletic club from school age could predict serum-free testosterone (FT) levels. Methods: The subjects were 1609 middle-aged male outpatients aged 40 years or older (median: 61 years, interquartile range: 54-69) who visited our hospital. Participants had their FT values measured in the morning hours during the period from December 2007 to June 2009. A questionnaire survey on exercise habits was conducted at the same time as the measurements. The exercise habit questionnaire was created based on whether the patients belonged to an athletic club in (a) elementary school, (b) junior high school, (c) high school, (d) college, (e) adult life, and (f) at the time of the test. Results: There was only one positive response to the questionnaire among 456 patients (28% of total), followed by zero for 358 patients (22% of total). The number of patients with low-testosterone levels (FT < 8.5 pg/mL) according to the Japanese diagnostic criteria for late-onset of hypogonadism was 839 (52.1%). In multivariate analysis, it was shown that with low-testosterone levels (FT < 8.5 pg/mL), age (odds ratio [OR]: 1.065, 95% confidence interval [CI]: 1.052-1.079; p < 0.001), hypertension (OR: 3.489, 95% CI: 2.728-4.462; p < 0.001), type-2 diabetes (OR: 3.035, 95% CI: 2.296-4.01; p < 0.001), and dyslipidemia (OR: 2.039, 95% CI: 1.558-2.668; p < 0.001) were risk factors, and more than two positive responses to the questionnaire (OR: 0.886, 95% CI: 0.802-0.980; p = 0.018) were also a significant independent factor. Conclusion: A sports club membership during school years may affect future testosterone levels.

Efficacy and Safety of First-Line Cytokines versus Sunitinib and Second-Line Axitinib for Patients with Metastatic Renal Cell Carcinoma (ESCAPE Study): A Phase III, Randomized, Sequential Open-Label Study.

BACKGROUND: The sequence of first-line cytokine and second-line molecular targeted therapies may be suitable for some patients with metastatic renal cell carcinoma (mRCC) because of the expectation of complete remission and durable response achieved with cytokine therapy. METHODS: This was a phase III randomized controlled trial investigating the outcomes of low-dose interleukin-2 (IL-2) plus interferon alfa (IFNα) versus sunitinib as the first line and axitinib as the second line in patients with low- and intermediate-risk mRCC. RESULTS: Thirty-five patients were randomly assigned. The total progression-free survival (PFS) to the end of the second line was 29.0 months (95% CI, 11.7-46.3) in the IL-2 + IFNα group and 16.3 months (95% CI, 6.3-26.4) in the sunitinib group. The PFS hazard ratio for the IL-2 + IFNα group relative to the sunitinib group was 0.401 (95% CI, 0.121-1.328; p = 0.135). The hazard ratio for overall survival (OS) was 1.675 (95% CI, 0.418-6.705; p = 0.466), which was better in the sunitinib group than in the IL-2 + IFNα group but not statistically significant. The types of adverse events (AEs) differed significantly, although there was no significant difference in the incidence of AEs. CONCLUSIONS: There was a trend toward better total PFS for IL-2 + IFNα, but it was not significant. There was also no advantage of IL-2 + IFNα in terms of OS. The study was underpowered to draw any definitive conclusions. The results showed no clear advantage of IL-2 + IFNα over sunitinib in the first-line setting; however, it may be an option in some relatively low-risk mRCC cases due to the difference in the AE profile. This trial was registered with the University Hospital Medical Information Network (UMIN), center identifier UMIN 000012522.

Novel α-Trifluoromethyl Chalcone Exerts Antitumor Effects Against Prostate Cancer Cells.

BACKGROUND/AIM: Despite treating advanced prostate cancer (PCa) with androgen deprivation therapy, it eventually progresses to castration-resistant PCa. Subsequently, taxanes are administered, but when PCa becomes resistant to taxanes, another treatment is needed, which has not yet been established. We previously synthesized a novel α-trifluoromethyl chalcone, YS71, and reported its antitumor effects against PCa cells. In this study, we confirmed its efficacy against androgen-sensitive, androgen-independent, and taxane-resistant PCa cells. MATERIALS AND METHODS: The PCa cell lines used were LNCaP, PC-3, DU145, PC-3-TxR (paclitaxel-resistant), PC-3-TxR/CxR (paclitaxel- and cabazitaxel-resistant), DU145-TxR, and DU145-TxR/CxR. The antiproliferative effects of YS71 were evaluated using proliferation assay. The reverse transcriptase transcription-polymerase chain reaction and western blot were performed to determine the expression level of androgen receptor (AR), whereas luciferase assay was performed to determine the AR activity. Furthermore, TUNEL assay and western blot were performed to investigate the mechanism of the antiproliferative effect. RESULTS: YS71 exerted a dose-dependent antitumor effect, inhibited AR activity, and induced apoptosis in all PCa cells in a dose-dependent manner. Western blot showed that YS71 increased the levels of apoptosis-related proteins, cleaved caspase-3, and cleaved PARP, and decreased the levels of the antiapoptotic proteins, Bcl-xL and Bcl-2. In addition, microarray analysis revealed that YS71 decreased several cancer-related genes. CONCLUSION: YS71 exhibits antitumor activity by inducing apoptosis in PCa cells, including taxane-resistant cells. It could be a potential future therapeutic option for hormone- and chemotherapy-resistant PCa.

Comparison of postoperative urinary continence and incontinence types between conventional and Retzius-sparing robot-assisted radical prostatectomy.

AIMS: This study aimed to investigate the postoperative urinary continence rate and incontinence types compared over time between conventional robot-assisted radical prostatectomy (C-RARP) and Retzius-sparing RARP (RS-RARP). METHODS: All 61 cases were selected from the C-RARP and RS-RARP by propensity score matching, and the pad scale, 24-h pad weight test, and International consultation on incontinence questionnaire-short form (ICIQ-SF) were followed-up over time up to 12 months. RESULTS: The probability of urinary continence per pad scale evaluation differed according to how it was defined: the continence rate 12 months after C-RARP and RS-RARP were 94% and 95% for 1 pad/day, 85% and 92% for 1 security pad/day, 61% and 85% for no pad use, respectively, which were all significantly better with RS-RARP. The results of the 24-h pad weight test were significantly better with RS-RARP at both 3 and 12 months, with median C-RARP versus RS-RARP values of 5 versus 1 g and 2 versus 0 g, respectively. In terms of types of urinary incontinence, the rates of postoperative stress urinary incontinence (SUI) increased in both procedures but to a lesser extent in RS-RARP. Other types of urinary incontinence, such as urge incontinence and terminal dribbling, did not differ significantly before and after surgery and between the two procedures. CONCLUSIONS: Postoperative urinary continence was better with RS-RARP than with C-RARP per all follow-up parameters until 12 months postoperatively. Postoperative SUI was significantly lower with RS-RARP than with C-RARP, which was considered the main reason for better postoperative urinary continence with RS-RARP.

Sarcopenia Is Associated With Aggressive Clinicopathological Outcomes and Is a Poor Prognostic Indicator for Non-metastatic Renal Cell Carcinoma.

BACKGROUND/AIM: We aimed to describe the impact of preoperative sarcopenia on the oncological outcome of non-metastatic renal cell carcinoma (RCC) after surgical treatment. PATIENTS AND METHODS: Data on 299 Japanese patients with non-metastatic RCC who underwent radical treatment at Kanazawa University Hospital between October 2007 and December 2018 were extracted. Clinicopathological features and survival prognosis of patients stratified by the presence or absence of sarcopenia as indicated by the psoas muscle mass index (PMI) were retrospectively analyzed. PMI <516.8 and <235.1 mm2/m2 at the L3 level for male and female were defined as the cutoff values for sarcopenia, respectively. RESULTS: Of 299 patients, 113 (37.8%) were classified as sarcopenic. The sarcopenia group showed a larger tumor size, worse pathological tumor stage and histological grade, and more frequent lymphovascular invasion than the non-sarcopenia group. According to Kaplan-Meier curves, sarcopenia was associated with a shorter overall survival (OS) and metastasis-free survival (p=0.0174 and 0.0306, respectively). Multivariate analysis identified sarcopenia as a significant and independent prognostic factor for poor OS (hazard ratio, 2.58; 95% confidence interval=1.09-6.08; p=0.030). CONCLUSION: Sarcopenia is a significant factor indicating worse pathological outcomes and poor survival prognosis in surgically treated non-metastatic RCC.

Intravesical BCG therapy with photodynamic diagnosis-guided transurethral resection of bladder tumors improves recurrence-free survival.

BACKGROUND: Intravesical Bacille Calmette-Guerin (BCG) therapy has been reported to be effective in preventing recurrence and progression in non-muscle invasive bladder cancer. Furthermore, photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumor (TURBT) improves the accuracy of cancer diagnosis and contributes to lower recurrence rates. The purpose of this study is to investigate whether more tumor resection with PDD-TURBT rather than conventional TURBT before BCG therapy outweighs the benefit of BCG therapy alone. METHODS: Patients who underwent intravesical BCG therapy following TURBT in our institution from 2010 to 2021 were included. They were divided into the following two groups: those who received PDD-TURBT before BCG treatment (PDD + BCG group) and those who received conventional TURBT before BCG treatment (WL + BCG group). The 2-year recurrence-free survival (RFS) and progression-free survival (PFS) of the two groups were retrospectively analyzed and compared. RESULTS: The 2-year RFS was significantly improved in the PDD + BCG group (hazard ratio [HR]: 2.41, 95% confidence interval [CI]: 1.26-4.60; p = 0.025). No significant difference in 2-year PFS was noted between the two groups. Analysis of prognostic factors for RFS showed that PDD-TURBT w We think that this text does not adequately express the meaning that we want to deliver to the reader.as a significant prognostic factor in univariate analysis (HR: 0.41, 95% CI: 0.18-0.92; p = 0.03). CONCLUSION: BCG treatment following PDD-TURBT significantly improved RFS more than BCG therapy following WL-TURBT. More accurate tumor localization and more efficient tumor resection by PDD-TURBT may have a positive impact on subsequent BCG treatments even if the treatment is administered postoperatively.

Postoperative functional and cancer control evaluation of conventional and Retzius-sparing robot-assisted radical prostatectomy: Comparison of selected cases by propensity score matching.

AIM: Although many reports have shown that Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) is effective for postoperative urinary continence, the postoperative voiding status and sexual function associated with this technique have not yet been adequately compared with those associated with conventional RARP (C-RARP). In this study, the lower urinary tract function, erectile function, and cancer control after C-RARP and RS-RARP were compared chronologically. MATERIALS AND METHODS: We selected 50 cases of C-RARP and RS-RARP each by propensity score matching and evaluated them over time using various questionnaires. Urinary continence recovery rates and biochemical recurrence (BCR)-free survival rates were calculated using the Kaplan-Meier method and compared between the two groups using the log-rank test. RESULTS: When urinary continence was defined as 0 pads per day, 0 pads per day + 1 security linear, or ≤1 pad per day, the postoperative improvement in urinary continence was better with RS-RARP over the course of up to 1 year for all definitions. The International Consultation on Incontinence Questionnaire-Short Form total scores and the Overactive Bladder Symptom Scores were better in the postoperative RS-RARP group. There were no significant differences in the International Prostate Symptom Score total score, QOL score, and erectile hardness score between the two groups during the observation period. The BCR-free survival did not differ significantly between the two groups CONCLUSIONS: Postoperative urinary continence was better in the RS-RARP group than in the C-RARP group; however, the voiding function, erectile function, and cancer control did not differ significantly.

Comparison of the Prognostic Value of Inflammatory and Nutritional Indices in Nonmetastatic Renal Cell Carcinoma.

Several markers that reflect inflammation and nutritional status have been associated with oncological outcomes in many tumors. This study aimed to describe the impact of pretreatment inflammatory and nutritional indices on the oncological outcomes in nonmetastatic renal cell carcinoma (RCC). A total of 213 Japanese patients with nonmetastatic RCC at Kanazawa University Hospital between October 2007 and December 2018 were included. The inflammatory and nutritional indices, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein-to-albumin ratio (CAR), prognostic nutritional index (PNI), and geriatric nutritional risk index (GNRI), were retrospectively analyzed. The optimal cutoffs for NLR, PLR, CAR, PNI, and GNRI were 2.18, 153.7, 0.025, 48.4, and 98, respectively. According to Kaplan-Meier curves, elevated NLR, PLR, CAR, and GNRI correlated with increased metastasis, while NLR and PNI correlated with worse overall survival (OS). In multivariate analysis, high CAR was an independent poor risk factor for metastasis (hazard ratio (HR), 3.08; 95% confidence interval (CI), 1.24-7.67; p = 0.016). Furthermore, high NLR showed an independent prognostic factor for worse OS (HR, 3.96; 95% CI, 1.01-15.59; p = 0.049). The pretreatment inflammatory and nutritional indices such as NLR and CAR might be promising prognostic factors for nonmetastatic RCC.

Is it Necessary to Treat all Metastatic Prostate Cancer With Upfront Androgen Receptor Axis-targeted Agents?

BACKGROUND/AIM: In recent years, initial treatment for patients with high-risk metastatic castration-sensitive (mCS) prostate cancer (PC) has been shifting from vintage hormone therapy to upfront androgen receptor axis-targeted agents (ARAT), but the proportion of Asian patients enrolled in clinical trials investigating the effectiveness of ARAT use is low. We examined the outcomes of Japanese patients with mCSPC who received ARAT as second-line therapy or afterwards. PATIENTS AND METHODS: Among the PC patients receiving treatment at Kanazawa University Hospital from 2000 to 2019, 190 patients with mCSPC were enrolled in the study. Their characteristics and prognosis were retrospectively investigated. RESULTS: All patients received androgen deprivation therapy (ADT) as initial treatment. A total of 142 (74.3%) of 190 patients had progression to castration-resistant PC (CRPC), of whom 77 (54.2%) received ARAT as second-line therapy or afterwards. The median overall survival (OS) of CRPC patients was 70.57 months and the median OS from CRPC was 44.88 months. The median OS of LATITUDE high-risk patients that used ARAT after the second-line treatment was 56.15 months, which was significantly longer than that of patients who did not use ARAT (hazard ratio=0.68, 95% confidence interval=0.40-1.15; p=0.0089). CONCLUSION: The prognosis of LATITUDE high-risk patients with CRPC selected for initial ADT therapy had a good prognosis compared to findings in other studies. These results suggest that there is a possibility that a certain number of patients with LATITUDE high-risk may have good prognosis even if only conventional ADT is performed and ARAT is used after CRPC.

Contribution of Retzius-sparing robot-assisted radical prostatectomy to the mechanism of urinary continence as demonstrated by dynamic MRI.

Retzius-sparing robot-assisted radical prostatectomy (RARP) has been reported to exhibit better postoperative urinary continence, but the reasons behind this are unknown. This study included 254 cases who underwent RARP and underwent postoperative dynamic MRI. We measured the urine loss ratio (ULR) immediately after postoperative urethral catheter removal and investigated its affecting factors and the mechanisms. Nerve-sparing (NS) techniques was performed in 175 (69%) unilateral and 34 (13%) bilateral cases, whereas Retzius-sparing in 58 (23%) cases. The median ULR early after indwelling catheter removal in all patients was 4.0%. The multivariate analysis was performed on factors that reduce ULR and found that the following factors were associated with ULR: younger age, NS and Retzius-sparing, which were significant. Additionally, dynamic MRI findings showed that membranous urethral length and the anterior rectal wall movement toward the pubic bone during abdominal pressure were significant factors. The movement observed on the dynamic MRI during abdominal pressure was thought to reflect an effective urethral sphincter closure mechanism. Long membranous urethral length and an effective urethral sphincter closure mechanism during abdominal pressure were considered effective for favorable urinary continence after RARP. NS and Retzius-sparing were clearly shown to have an additive effect in preventing urinary incontinence.

Suppression of androgen receptor signaling induces prostate cancer migration via activation of the CCL20-CCR6 axis.

The suppression of androgen receptor (AR) expression exacerbates the migration potential of prostate cancer. This study identified a previously unrecognized regulation of the AR-controlled pathway that promotes migration potential in prostate cancer cells. Prostate cancer cells that pass through a transwell membrane (mig cells) have a higher migration potential with a decreased AR expression than parental cells. In this study, we aimed to elucidate the mechanism of migration enhancement associated with the suppression of AR signaling. Expression of C-C motif ligand 20 (CCL20) is upregulated in mig cells, unlike in the parental cells. Knockdown of AR with small interfering RNA (siAR) in LNCaP and C4-2B cells increased CCL20 secretion and enhanced the migration of cancer cells. Mig cells, CCL20-treated cells, and siAR cells promoted cell migration with an enhancement of AKT phosphorylation and Snail expression, while the addition of a C-C chemokine receptor 6 (CCR6, the specific receptor of CCL20) inhibitor, anti-CCL20 antibody, and AKT inhibitor suppressed the activation of AKT and Snail. With 59 samples of prostate cancer tissue, CCL20 secretion was profuse in metastatic cases despite low AR expression levels. Snail expression was associated with the expression of CCL20 and CCR6. A xenograft study showed that the anti-CCL20 antibody significantly inhibited Snail expression, thereby suggesting a new therapeutic approach for castration-resistant prostate cancer with the inhibition of the axis between CCL20 and CCR6.

Decreased febrile neutropenia during inpatient chemotherapy for urologic cancer during coronavirus disease 2019 pandemic.

Since 2020, the coronavirus disease 2019 pandemic has led to the widespread practice of hand hygiene and wearing face masks, not only among medical personnel, but also among the general population. Thus, the impact of the coronavirus disease 2019 pandemic on the incidence of febrile neutropenia should be verified. This study aimed to examine the incidence of febrile neutropenia in hospitalized patients receiving chemotherapy at Kanazawa University Hospital. Among inpatients at the Department of Urology receiving chemotherapy, we compared the incidence of febrile neutropenia between 317 cases in 2018-2019 and 276 cases in 2020. We retrospectively analyzed the factors of febrile neutropenia via binomial logistic regression analysis based on patient characteristics and the characteristics of primary diseases, with statistical significance set at p < 0.05. Febrile neutropenia occurred in 20/317 cases in 2018-2019 and 1/276 cases in 2020, with a significant decrease in the latter (p = 0.005). In a multivariate analysis, we identified the following independent risk factors for febrile neutropenia: non-coronavirus disease 2019 era (p = 0.005), first course of therapy (p = 0.005), malnutrition (p = 0.032), and past history of febrile neutropenia (p = 0.018). Due to the coronavirus disease 2019 pandemic, hygiene policies for medical personnel and quarantine measures for patients were thoroughly implemented. Therefore, the incidence of febrile neutropenia in 2020 decreased to 1/15 of the previous incidence. Thus, the hygiene for medical personnel and patients during the expected period of chemotherapy-induced neutropenia is important for febrile neutropenia prevention.

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.

Does Bladder Cancer with Inchworm Sign Indicate Better Prognosis after TURBT?

Background: Inchworm sign is considered to be a characteristic finding in non-muscle invasive bladder cancer (NMIBC). Nevertheless, pathologically diagnosed muscle invasive bladder cancers (MIBCs) are occasionally diagnosed from tissue obtained by transurethral resection of bladder tumor (TURBT) in patients with inchworm sign. Methods: We retrospectively investigated the factors related to muscle invasive status in bladder cancer associated with inchworm sign and the role of inchworm sign in tumor outcomes following TURBT. Results: Of the 109 patients with inchworm sign, 94 (86.2%) and 15 (13.8%) were NMIBC and MIBC, respectively. Non-papillary tumors (hazard ratio (HR): 9.55, 95% confidence interval (CI): 2.07−44.10; p < 0.01) and tumors located in the bladder neck (HR: 7.73, 95% CI: 1.83−32.76; p < 0.01) were significant predictors of MIBC in bladder cancer with inchworm sign. Furthermore, recurrence-free survival (RFS) and progression-free survival were compared between patients with NMIBC with and without inchworm sign; however, no significant differences were found. In patients with NMIBC with inchworm sign, positive urine cytology was a prognostic factor for RFS (HR: 1.90, 95% CI: 1.04−3.48; p = 0.04). Conclusions: In bladder cancer with inchworm sign, 86.2% were NMIBC. Even in the case of inchworm sign, the presence of a non-papillary tumor or a bladder neck tumor before TURBT should be noted because of the possibility of MIBC. In this study, the inchworm sign was not a prognostic factor in patients with NMIBC.