Increased level of serum leucine-rich-alpha-2-glycoprotein 1 in patients with clear cell renal cell carcinoma.

BACKGROUND: Currently, no useful serum markers exist for clear cell renal cell carcinoma (ccRCC), making early detection challenging as diagnosis relies solely on imaging tests. Radiation exposure is also a concern due to multiple required CT examinations during treatment. Renal cell carcinoma (RCC) histological types include ccRCC and non-clear cell RCC (non-ccRCC); however, treatment response to medications varies which necessitates accurate differentiation between the two. Therefore, we aimed to identify a novel serum marker of RCC. Increased LRG1 expression in the serum has been demonstrated in multiple cancer types. However, the expression of LRG1 expression in the serum and cancer tissues of patients with RCC has not been reported. Since ccRCC is a hypervascular tumor and LRG1 is capable of accelerating angiogenesis, we hypothesized that the LRG1 levels may be related to ccRCC. Therefore, we examined LRG1 expression in sera from patients with RCC. METHODS: Using an enzyme-linked immunosorbent assay, serum levels of leucine-rich-alpha-2-glycoprotein 1 (LRG1) were measured in 64 patients with ccRCC and 22 patients non-ccRCC who underwent radical or partial nephrectomy, as well as in 63 patients without cancer. RESULTS: Median values of serum LRG1 and their inter-quartile ranges were 63.2 (42.8-94.2) µg/mL in ccRCC, 23.4 (17.7-29.6) µg/mL in non-ccRCC, and 36.0 (23.7-56.7) µg/mL in patients without cancer, respectively (ccRCC vs. non-ccRCC or patients without cancer: P < 0.001). C-reactive protein (CRP) levels (P = 0.002), anemia (P = 0.037), hypercalcemia (P = 0.023), and grade (P = 0.031) were independent predictors of serum LRG1 levels in ccRCC. To assess diagnostic performance, the area under the receiver operating characteristic curve of serum LRG1 was utilized to differentiate ccRCC from non-cancer and non-ccRCC, with values of 0.73 (95% CI, 0.64-0.82) and 0.91 (95% CI, 0.82-0.96), respectively. CONCLUSIONS: LRG1 served as a serum marker associated with inflammation, indicated by CRP, anemia, hypercalcemia, and malignant potential in ccRCC. Clinically, serum LRG1 levels may assist in differentiating ccRCC from non-ccRCC with excellent diagnostic accuracy.

Ex Vivo Partial Nephrectomy and Autotransplantation for Complex and Multifocal Renal Cell Carcinoma at a Single Institution: A Case Series.

Renal autotransplantation is a rare surgical procedure designed to preserve renal function in patients with complex urinary system diseases or highly complex renal tumors. Between 2012 and 2023, four patients underwent ex vivo partial nephrectomy (PN) and autotransplantation for complex renal tumors at our hospital. Two patients had bilateral multifocal renal tumors, including von Hippel Lindau (VHL) disease and hybrid oncocytic chromophobe tumor (HOCT). The remaining two patients had highly complex renal tumors with Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) score of 12, one of whom had a solitary kidney. None of the patients experienced any postoperative surgical complications. Pathologically, nine of the excised tumors had negative surgical margins, except for one of the four tumors on HOCT. Postoperative renal function decreased at one month compared to preoperative renal function (P = 0.01); however, there was no significant difference at three months (P = 0.07). None of the patients had a local recurrence or metastasis at the latest follow-up.Ex vivo PN and autotransplantation are feasible and reasonable treatment methods for highly complex and multifocal renal tumors regarding safety, local tumor control, and preservation of renal function.

Clinicopathological characteristics of adrenocortical carcinoma in the Kyushu-Okinawa area of Japan.

OBJECTIVE: Adrenocortical carcinoma is a rare condition, with limited comprehensive reports from Japan. This study aimed to review Japan's data on adrenocortical carcinoma by assessing information from 46 patients-with adrenocortical carcinoma across 10 Japanese university hospitals. METHODS: We conducted a retrospective multi-institutional analysis of the clinical characteristics of adrenocortical carcinoma in Japan. We evaluated data from 46 patients across 10 university hospitals over 10 years and analyzed the relationship between clinicopathological characteristics and overall survival. RESULTS: Five- and 10-year overall survival rates were 59% and 53%, respectively. Overall survival was significantly different among the tumor-node-metastasis system for adrenocortical carcinoma of the American Joint Committee on Cancer/International Union Against Cancer, with the worst prognosis in stage IV (p = 0.0044). In our cohort, neither the Weiss score nor the Ki-67 proliferation index correlated with overall survival. Adjuvant treatment did not yield improved overall survival, whereas resection of the primary tumor in stage IV disease was significantly associated with improved overall survival (p = 0.0262). Out of the cases evaluated for plasma hormones, plasma cortisol, aldosterone, testosterone, and DHEA-S levels were measured at 23%, 42%, 29%, and 62%, respectively, demonstrating higher levels than the upper normal limits. CONCLUSION: Patients with stage IV adrenocortical carcinoma had a poor prognosis; however, resection of the primary tumor in stage IV disease was associated with prolonged survival. The results of this study are expected to contribute to future treatment of adrenocortical carcinoma in Japan.

Real-world treatment outcomes of patients with penile cancer in the Kyushu-Okinawa area of Japan in the pre-guideline era.

OBJECTIVES: To understand the real-world outcomes for patients with penile cancer in the Kyushu-Okinawa area before the introduction of practice guidelines in Japan. METHODS: We retrospectively collected medical information on patients with penile squamous cell carcinoma and penile intraepithelial neoplasia at 12 university hospitals and their affiliated hospitals in the Kyushu-Okinawa area from January 2009 to December 2020. Patients with unknown clinical stage were excluded. Patient background characteristics and survival, as well as pretreatment factors involved in survival, were investigated. RESULTS: A total of 196 patients were included. Patients with clinical stage 0, I, IIA, IIB, IIIA, IIIB and IV comprised 9.7, 26.0, 22.4, 2.6, 10.7, 14.3 and 14.3%, respectively. The median follow-up was 26 months, and the mean 5-year overall survival and cancer-specific survival rates were 74.3 and 79.8%, respectively. On univariate analysis, tumor diameter ≥ 30 mm, penile shaft tumor, Eastern Cooperative Oncology Group performance status ≥ 1, cT ≥ 3, cN ≥ 2 and cM1 were associated with significantly poorer cancer-specific survival. On multivariate analysis, pretreatment factors of cN ≥ 2 (hazard ratio, 32.5; 95% confidence interval, 5.08-208; P = 0.0002), Eastern Cooperative Oncology Group performance status ≥ 1 (4.42; 1.79-10.9; P = 0.0012) and cT ≥ 3 (3.34; 1.11-10.1; P = 0.0319) were identified as independent prognostic factors. CONCLUSIONS: The study revealed basic data for future penile cancer treatment and research, including survival rates according to clinical stages, and identified cN ≥ 2, Eastern Cooperative Oncology Group performance status ≥ 1 and cT ≥ 3 at initial diagnosis as independent prognostic factors. Evidence for penile cancer in Japan is particularly scarce, and future large-scale prospective studies are warranted.

Profile of gut microbiota and serum metabolites associated with metabolic syndrome in a remote island most afflicted by obesity in Japan.

Numerous studies have revealed distinct differences in the profiles of gut microbiota between non-obese and obese individuals. To date, however, little is known if any disparities in the community of gut microbiota exist between metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO) subjects. We therefore aimed to comprehensively characterize the gut microbiota and circulating metabolites in serum from both MHO and MUO residing in the remote island, Kumejima, where the prevalence of obesity is one of the highest in Japan, and explored possible correlations between the gut microbiota profile and markers of metabolic syndrome. Results revealed that MUO showed significantly higher levels of genera such as g_Succinivibrio, g_Granulicatella, g_Brachyspira, g_Oribacterium and g_Atopobium in comparison to MHO. Moreover, abundance of g_Succinivibrio, g_Brachyspira and g_Atopobium were positively correlated with value of fasting insulin, HOMA-R, circulating triglycerides, diastolic blood pressure, BMI, body weight, waist circumference and HbA1c. In addition, MUO compared to MHO showed an imbalance of serum metabolites, with a significant elevation in 2-oxoisovaleric acid, pyruvic acid, 2-hydroxybutyric acid, and creatine. Our data highlight unmet needs in precision approaches for the treatment of obesity, targeting the gut microbiota profile and serum metabolites in a distinct population affected by obesity.

Summary of the Clinical Practice Guidelines for Penile Cancer 2021 by the Japanese Urological Association.

Penile cancer is a rare cancer for which no medical guidelines have been established before in Japan. These guidelines aim to standardize, as much as possible, the therapeutic modality for penile cancer, for which empirical evidence is limited on a global scale, thereby bolstering therapeutic outcomes for patients with penile cancer. The new guidelines conform to the Minds Guide for Developing Clinical Practice Guidelines (2017) as much as possible. However, virtually no randomized comparative studies and meta-analyses based on such randomized studies have been conducted. Therefore, only the findings available at present were listed after conducting an exhaustive literature review of items with extremely low evidence levels and for which bodies of evidence and grades of recommendation were not evaluated. Clinical questions were set for items with a relatively large number of studies, including retrospective studies. However, since it is virtually impracticable to summarize bodies of evidence by systematic reviews, recommendation grades and evidence levels were discussed and determined by the consensus panel of the Preparatory Committee. The following were outlined: epidemiological, pathological, diagnostic, therapeutic, follow-up, and quality of life-related findings. Additionally, seven clinical questions were established to determine recommendation grades and evidence levels. We hope that these guidelines will prove to be useful to medical professionals engaged in clinical practice related to penile cancer in Japan and anticipate that critical reviews of the guidelines will lead to further refinement of the next edition.

Serum IgG4 Concentration Is a Potential Predictive Biomarker in Glucocorticoid Treatment for Idiopathic Retroperitoneal Fibrosis.

OBJECTIVES: To evaluate the management and outcome of idiopathic retroperitoneal fibrosis (iRPF) in Japan, and to identify its clinical biomarker. METHODS: We retrospectively analyzed 129 patients with iRPF treated between January 2008 and May 2018 at 12 university and related hospitals. Patients treated with glucocorticoid were analyzed to identify a predictive biomarker. These patients were classified into three groups according to overall effectiveness (no change: NC, complete response: CR, and partial response groups: PR), and each parameter was compared statistically. RESULTS: Male-female ratio was 5:1, and median age at diagnosis was 69 (33-86) years. Smoking history was reported in 59.6% of the patients. As treatment, 95 patients received glucocorticoid therapy with an overall response rate of 84%. As a result, serum concentration of IgG4 was significantly decreased in NC group compared with the other two groups (56.6 mg/dL vs. 255 mg/dL, 206 mg/dL, p = 0.0059 and 0.0078). ROC analysis was performed between the nonresponder (NC) and responder groups (CR + PR) to identify the cut-off value of serum IgG4 as a predictive marker. As a result, AUC of 0.793 was confirmed. CONCLUSIONS: Pre-treatment serum IgG4 concentration may have potential as a predictive biomarker of steroid treatment.

Obesity and Voiding Parameters in a Community-Based Population of Okinawa, Japan: Kumejima Digital Health Project (KDHP).

(1) Background: Evidence has accumulated regarding the etiology of lower urinary tract symptoms associated with obesity and metabolic syndrome. Therefore, the present study aimed to identify which subjectively and objectively measured voiding parameters were associated with obesity in a community-based population. (2) Methods: Voiding parameters on a self-administered questionnaire and a digital self-health monitoring system for urine excretion (s-HMSU) were compared between participants with and without obesity, defined as a body mass index ≥ 25 kg/m2 (n = 30 and 29, respectively), from a community in Okinawa, Japan. Logistic regression analysis was employed to calculate the odds ratios of abnormalities in voiding parameters for the obese group, with the non-obese group serving as a reference. (3) Results: The obese group had odds ratios of 5.17 (95% confidence interval: 1.33−20.0) for shortened hours of undisturbed sleep (<302 min) by s-HMSU and 7.65 (1.88−31.1) for nighttime urinary frequency by a questionnaire after adjusting for age and sex. In addition, the obese group had an adjusted odds ratio of 2.27 (0.76−6.78) for decreased maximum bladder capacity (<212 mL) by s-HMSU. (4) Conclusion: the results of the present study suggest that nocturia and shortened hours of undisturbed sleep are signs of obesity.

Efficacy of Pre-operative 18F-FDG PET/CT in Prognostic Prediction in Patients With Renal Cell Carcinoma.

Background/Aim: This study analyzed the parameters provided by preoperative 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for prognostic prediction of renal cell carcinoma (RCC). Patients and Methods: FDG-PET/CT data from 66 clear cell RCC and 19 non-clear cell RCC cases between January 2015 and October 2018 were reviewed retrospectively. We compared the two groups according to recurrence/metastasis to determine prognosis-influencing factors. Multivariate Cox hazard regression models were constructed to evaluate factors potentially predicting disease-free survival (DFS) after adjustment for confounders. DFS was then compared between groups. Results: Standardized uptake values (SUV) of the PET/CT scan were independent predictors of prognosis after adjusting for confounders. RCC cases were divided into two groups by optimal cut-off values. Differences between DFS percentages in high and low SUV groups were significant. Similar results were obtained in clear cell RCC groups. Conclusion: Increased SUV of the PET/CT scan are significant predictors of worse prognoses in patients with surgically resected RCC.

Evaluation of the Influence of a History of Childhood Nocturnal Enuresis on Nighttime Urinary Frequency and the Causes of Nocturia in Adults.

OBJECTIVE: To examine whether a history of nocturnal enuresis affects nighttime urinary frequency and to evaluate nocturia etiologies in adults. MATERIALS AND METHODS: A total of 143 participants with at least one episode of nocturia per night were included in this study. The self-reported questionnaire collected data on demographic characteristics, medical history, history of nocturnal enuresis in elementary school, lower urinary tract symptoms, and frequency-volume charts. RESULTS: A history of nocturnal enuresis was observed in 52.4% of participants. However, night-time urinary frequency was significantly lower in participants with a history of nocturnal enuresis in elementary school than in those without such history. On multivariate analysis, a history of nocturnal enuresis was also negatively associated with nighttime urinary frequency (P <.01). There was a collinearity effect between age and nighttime urinary frequency. A history of nocturnal enuresis did not affect the presence of nocturnal polyuria or overactive bladder in participants. However, sleep disturbances were fewer in participants with a history of nocturnal enuresis (odds ratio 0.404). CONCLUSION: A history of nocturnal enuresis might be negatively associated with nighttime urinary frequency due to fewer sleep disturbances. Further, progression of nocturia may depend on conditions, such as age and acquired diseases.

Coexisting congenital mid-ureteral stricture and megaureter due to ureterovesical junction obstruction: A case report.

Congenital mid-ureteral strictures (CMS) are rare. Most congenital strictures occur at the ureteropelvic junction or ureterovesical junction, with mid-ureteral strictures accounting for only 4-5% of all cases of ureteral obstruction in children. Furthermore, there are very few reports of coexisting mid-ureteral stricture and ureterovesical junction obstruction (UVJO). Here, we report a case of coexisting UVJO and CMS. CMS was not detected on preoperative magnetic resonance imaging, and hydronephrosis remained after ureteroneocystostomy. Therefore, MRI was repeated and CMS was diagnosed, for which we performed ureteroureterostomy. Intraoperative retrograde pyelography (RGP) aids definitive diagnosis of UVJO.

Large adrenocortical adenoma with malignant features on imaging: A case report.

Large adrenocortical adenomas have rarely been reported. We describe a case of a 26-year-old man who underwent an adrenalectomy for a large adrenocortical adenoma (8.6 × 7.7 cm). Although the lesion had typical malignant features on imaging, histopathological examination revealed an adrenocortical adenoma. This highlights that imaging alone may not be able to distinguish adrenocortical carcinomas from adrenal masses. In most cases, a resection should be performed for early diagnosis and management of large adrenal masses with malignant features on imaging. To our knowledge, this is the first report of a large adrenocortical adenoma diagnosed with multiple imaging investigations.

Initial dose reduction of enzalutamide does not decrease the incidence of adverse events in castration-resistant prostate cancer.

BACKGROUND: There was no clear evidence whether the initial dose of enzalutamide affects the incidence of adverse events (AEs), and oncological outcome in patients with castration-resistant prostate cancer (CRPC). METHODS: The clinical charts of 233 patients with CRPC treated with enzalutamide were reviewed retrospectively. After 1:3 propensity score matching (PSM), 124 patients were divided into a reduced dose group and a standard dose group, and the prostate specific antigen (PSA) response and the incidence of AEs were compared. RESULTS: 190 patients with CRPC initiated with standard dose enzalutamide were younger and better performance status compared with 43 patients beginning with reduced dose. After PSM, the baseline characteristics were not different between the standard and the reduced dose group. In the PSM cohort, the PSA response rate was significantly lower in the reduced dose group than in the standard dose group (-66.3% and -87.4%, p = 0.02). The incidence rates of AEs were not statistically different between the groups (22.6% and 34.4%, respectively, p = 0.24). CONCLUSION: Initiating treatment with a reduced dose of enzalutamide did not significantly decrease the incidence rate of AEs, and it showed poorer PSA response rate. There is no clear rationale for treating with a reduced initial dose of enzalutamide to reduce the incidence of AEs.

Surveillance of urachal abscess in the Kyushu-Okinawa area of Japan.

OBJECTIVE: To report a multicenter experience with the management of urachal abscess treatment in Japan. METHODS: This was a retrospective study of 263 cases of urachal abscess managed at 12 university hospitals in the Kyushu-Okinawa region over a 10-year period. Age, sex, abscess size, clinical symptoms, type of urachal remnants, and treatment were collected and analyzed. RESULTS: The average age was 29.8 ± 18.1 years, with males accounting for approximately two-thirds of the study population. The average abscess size was 1.7 cm (range 0-11 cm). The most common presenting symptom was umbilical secretion (66%), followed by abdominal pain (46%). A total of 127 patients (48.3%) were treated with antibiotics alone, whereas 136 patients (51.7%) received surgical treatment. The surgical approach was laparotomy in 75 patients (61.0%) and laparoscopic surgery in 48 patients (39.0%). Regarding the type of urachal remnant, the urachus sinus (180 patients) accounted for 68.4% of the total. CONCLUSIONS: To our knowledge, this study represents the first report on urachal abscess treatment in Japan. Our data show that the clinical symptoms might vary depending on the type of urachus remnant. It should be noted that gross hematuria, a characteristic symptom of urachal cancer, is rare in patients with urachal abscess.

Stage-specific Embryogenic Antigen-4 Expression in Castration-resistant Prostate Cancer and its Correlation With the Androgen Receptor.

BACKGROUND/AIM: Stage-specific embryonic antigen (SSEA)-4 plays important roles in the malignant aggressiveness of various cancers. The aim of this study was to investigate the pathological characteristics of SSEA-4 in castration-resistant prostate cancer (CRPC). MATERIALS AND METHODS: SSEA-4 expression and its pathological roles were evaluated in five prostate cancer (PC) cell lines and 27 CRPC tissues. The relationship between SSEA-4 and the androgen receptor (AR) was also examined. RESULTS: SSEA-4 expression was detected in AR-negative cells (PC3, DU145, and AICaP1) but was not detected in AR-positive cells (LNCaP and AICaP2). SSEA-4 expression in human CRPC tissues was significantly higher than that in locally advanced or metastatic hormone sensitive PC (HSPC) tissues. A negative correlation was also detected between SSEA-4 and AR in CRPC tissues but not in HSPC tissues. CONCLUSION: SSEA-4 was over-expressed in CRPC and the changes were mediated by complex mechanisms that related to the AR and hormonal therapy.

Three-month early change in prostate-specific antigen levels as a predictive marker for overall survival during hormonal therapy for metastatic hormone-sensitive prostate cancer.

OBJECTIVE: To date, there are no useful markers for predicting the prognosis of metastatic hormone-sensitive prostate cancer (mHSPC). We evaluated the effect of early changes in prostate-specific antigen (PSA) levels after androgen deprivation therapy (ADT) on castration-resistant prostate cancer (CRPC) progression and overall survival (OS) in mHSPC patients. RESULTS: In 71 primary mHSPC patients treated with ADT, the median times to CRPC and OS were 15 months and 92 months, respectively. In multivariate analysis, a Gleason score of ≥ 8 (p = 0.004), an extent of disease value (EOD) of ≥ 2 (p = 0.004), and a 3-month PSA level > 1% of the pretreatment level (p = 0.017) were independent predictors of shorter time to CRPC. The area under the receiver operating characteristic curve was feasible at 0.822. A 3-month PSA level > 1% of the pretreatment level was an independent predictor of OS (p = 0.004). Three factors were independent predictors of shorter time to CRPC. A 3-month PSA level > 1% of the pretreatment level correlated with a poor prognosis.

Hypophysitis induced by ipilimumab and nivolumab combination therapy for advanced renal cell carcinoma: A case report.

Ipilimumab and nivolumab combination therapy is effective against unresectable or metastatic renal cell carcinoma. However, it is associated with many immune-related adverse events, including hypophysitis that is difficult to diagnose early because of non-specific initial symptoms. Herein, we report the case of a 54-year-old man with metastatic renal cell carcinoma who developed hypophysitis after receiving ipilimumab and nivolumab combination therapy. The initial symptom was headache. However, endocrine tests showed decreased levels of cortisol, free thyroxine and thyroid-stimulating hormone. Moreover, magnetic resonance imaging revealed pituitary enlargement. Accordingly, we diagnosed hypophysitis and immediately started hydrocortisone replacement therapy, which improved the symptoms.

Effect of a mobile digital intervention to enhance physical activity in individuals with metabolic disorders on voiding patterns measured by 24-h voided volume monitoring system: Kumejima Digital Health Project (KDHP).

PURPOSE: To evaluate the effect of a mobile digital intervention on voiding patterns, we performed 24-h voided volume monitoring in individuals with metabolic disorders. METHODS: Participants with metabolic disorders were grouped into either the intervention group (n = 17), who had access to a smartphone app (CARADA), or the non-intervention group (n = 11), who did not. Urine monitoring was conducted for 24 h using a novel digital self-health monitoring system for urine excretion (s-HMSU). Body weight, abdominal circumference, blood pressure, and biomarkers were measured. RESULTS: Physical findings and blood test results at baseline and 6 months indicated no significant between-group differences. Night-time frequency did not change between baseline and 6 months in the intervention group but significantly worsened at 6 months in the non-intervention group, as compared to baseline (1.0 ± 0.7 vs. 1.5 ± 0.5, p < 0.05). The change in night-time frequency over 6 months did not differ between the intervention and non-intervention groups. Furthermore, the change in hours of undisturbed sleep over 6 months did not differ between the two groups. However, compared with baseline, nocturnal polyuria index tended to worsen at 6 months in the non-intervention group. CONCLUSION: Our study results suggest that mobile digital intervention might be useful for behavioral therapy to improve night-time frequency and urine production and that s-HMSU might be beneficial for confirming the prevention of progress in individuals with metabolic disorders, which can aid in modifying lifestyle.

Changes in urethral smooth muscle and external urethral sphincter function with age in rats.

To confirm changes in urethral activity with age, both intravesical pressure and urethral perfusion pressure (UPP) were recorded and external urethral sphincter electromyography (EUS-EMG) was performed. A total of 33 female Sprague Dawley rats aged 3 months (young rats), 12 months (middle-aged rats), and 24 months (aged rats) were used. Bladder activity was evaluated using continuous cystometry. Urethral activity was evaluated by simultaneously recording intravesical pressure and UPP in isovolumetric conditions under urethane anesthesia in each group. Additionally, EUS-EMG activity was monitored under the same conditions. In continuous cystometry, the amplitude of bladder contractions was not different among the three groups; nevertheless, residual urine volume was significantly increased in middle-aged and aged rats, as compared in young rats. With respect to UPP, the change in UPP was significantly smaller in aged rats (60%) and middle-aged rats (64%) than in young rats. Furthermore, the mean amplitude of high-frequency oscillations of the EUS was significantly lower in aged (61%) and middle-aged rats (70%) than in young rats. EUS-EMG revealed EUS bursting activity during voiding with clear active and silent phases in young rats but unclear active and silent phases in aged rats. Masson's trichrome staining of the urethra showed EUS atrophy in aged rats compared to young and middle-aged rats. The results indicate that aging induces two urethral dysfunctions in the urethral smooth muscle and EUS, which may lead to dyscoordination between the urinary bladder and urethra.

Urine Lactoferrin as a Potential Biomarker Reflecting the Degree of Malignancy in Urothelial Carcinoma of the Bladder.

Urothelial carcinoma of the bladder (UCB) is potentially life-threatening; therefore, we aimed to discover a novel urine biomarker for diagnosis and prognostication of UCB. This is a retrospective case-control study. Exploration of a new biomarker using urine from 20 UCB patients in the present study revealed that urinary level of lactoferrin (LF), a multifunctional glycoprotein released from neutrophils, was higher in 11 of 15 with invasive/high-grade UCB than 5 with non-invasive one, and 2 healthy adults. We therefore focused on LF and assessed the value of urine LF normalized by urine creatinine concentration (LF/Cr) using an enzyme-linked immunosorbent assay. Diagnostic performance of urine LF/Cr was examined using urine from 92 patients with primary (newly diagnosed) untreated UCB and 166 controls without UCB, including 62 patients with pyuria, and 104 subjects without pyuria consisting of 84 patients and 20 healthy adults. However, the diagnostic accuracies were accompanied by the risk of bias. In 92 primary UCB patients, both pyuria and tumor-infiltrating neutrophils (TINs) were independent predictors for urine LF/Cr. In contrast, TINs or urine LF/Cr were independent predictors for invasive histology, whereas pyuria was not. In terms of prognostication, urine LF/Cr and nodal metastasis were independent predictors of disease-specific survival in 22 patients with muscle-invasive bladder cancer, characterized by a high mortality rate, in the Cox proportional hazards model. In conclusion, urine LF/Cr linked to TINs was a predictor of both invasive histology and prognosis in UCB. Urine LF/Cr is a potential biomarker reflecting the degree of malignancy in UCB.