Comprehensive analysis of perioperative hypotension in photodynamic diagnosis-assisted transurethral resection of bladder tumor with 5-aminolevulinic acid.

OBJECTIVE: Intraoperative hypotension remains a serious adverse event of photodynamic diagnosis-assisted transurethral resection of bladder tumor with oral administration of 5-aminolevulinic acid. We conducted a re-analysis of perioperative hypotension in photodynamic diagnosis-assisted transurethral resection of the bladder tumor with oral 5-aminolevulinic acid to ascertain its safety. METHODS: A total of 407 cases who underwent transurethral resection of bladder tumors in our institution were reviewed (274 cases for the PDD group with photodynamic diagnosis and 133 for the white light (WL) group without). A classification of hypotension severity was devised to identify risk factors for clinically troublesome hypotension. The distribution of hypotension severity in each of the PDD and WL groups was compared. Additionally, the patient background and perioperative data by hypotension severity were compared only in the PDD group. RESULTS: More patients with moderate and severe hypotension were noted in the PDD group. The renal function was lower with increasing hypotension severity in the PDD group. More patients on general anesthesia were included in the mild and moderate hypotension group, whereas more patients on spinal anesthesia were included in the severe hypotension group. Furthermore, the frequency of side effects other than hypotension tended to increase with hypotension severity. CONCLUSIONS: Renal function impairment and the other adverse effects of 5-aminolevulinic acid may be risk factors for severe hypotension. Mild or moderate hypotension may be caused by general anesthesia and severe hypotension may be caused by spinal anesthesia. To elucidate specific risk factors, further case-control studies are warranted.

Bone Turnover Markers, n-Terminal Propeptide of Type I Procollagen and Tartrate-Resistant Acid Phosphatase Type 5b, for Predicting Castration Resistance in Prostate Cancer.

Bone is a common site of prostate cancer metastasis. Bone turnover markers n-terminal propeptide of type I procollagen (P1NP) and tartrate-resistant acid phosphatase type 5b (TRACP-5b) are highly sensitive to bone remodeling activity. However, their prognostic significance as markers of prostate cancer is unknown. This study retrospectively examined the usefulness of P1NP and TRACP-5b as prognostic biomarkers. Castration-resistant prostate cancer recurrence-free survival (CFS) was estimated using the Kaplan-Meier method. A predictive model for CFS was constructed using multivariate analysis. This study enrolled 255 patients diagnosed with prostate cancer at Kanazawa University Hospital. The median follow-up was 115.1 months. Patients with both high serum P1NP and TRACP-5b levels, defined as having a poor bone turnover category (BTC), had significantly shorter CFS. Multivariate analysis identified Gleason score, metastasis, and BTC poor as predictors for castration resistance in prostate cancer. Using these three factors, a prognostic model was established, categorizing patients into low-risk (no or one factor) and high-risk (two or three factors) groups. In the low-risk group, the median CFS was not reached, contrasting with 19.1 months in the high-risk group (hazard ratio, 32.23, p < 0.001). Combining P1NP and TRACP-5b may better predict castration resistance.

Procalcitonin in advanced urological cancer-bacterial versus non-bacterial infections: prospective cohort study.

OBJECTIVES: Patients with advanced cancer may develop bacterial infections (BI) as their general condition worsens, but general blood tests often find it difficult to distinguish them from non-bacterial infections (NBI). The present prospective study was undertaken to investigate the effectiveness of serum procalcitonin levels in distinguishing between BI and NBI in patients with advanced urological cancer. METHODS: This study prospectively evaluated patients diagnosed with locally advanced or metastatic or recurrent urological cancer in our department from September 2013 to December 2019. Body temperature was measured in the axilla and the measurement results were recorded. Febrile episodes of ≥38.0°C were analysed, and written patient consent was obtained at the onset of the fever. RESULTS: Of 75 patients enrolled in the present study, 90 febrile episodes were analysed. A total of 34 of 90 febrile episodes were regarded as BI, and the remaining 56 febrile episodes as NBI. The median procalcitonin value was significantly higher in the BI group (p=0.0015), while no significant difference was found between the two groups for white blood cell count and C reactive protein. Additionally, a white blood cell count of less than 1.0×10ˆ9/L resulted in BI in all cases. The procalcitonin receiver operating characteristic area under the curve was 0.710 (95% CI 0.586 to 0.83), excluding cases with white blood cell counts of <1.0 × 103/µL. CONCLUSIONS: Procalcitonin is a rapid and affordable marker for differentiation between BI and NBI in patients with advanced urological cancer.

Does radical cystectomy have a better prognosis than bladder conservative treatment in the real world?

PURPOSE: To compare the prognosis and quality of life between radical cystectomy and bladder conservative treatment for muscle invasive bladder cancer in the real world. MATERIALS AND METHODS: Patients treated for muscle invasive bladder cancer without metastases were retrospectively evaluated for overall survival, progression-free survival, and rehospitalization. RESULTS: Of the 141 patients, 62 underwent bladder conservative treatment and 79 underwent radical cystectomy. Patients who underwent radical cystectomy had significantly better progression-free survival (HR: 1.83, 95% CI: 1.12-3.00; p < 0.01) and overall survival (HR: 1.82, 95% CI: 0.99-3.34; p = 0.03) than those who underwent conservative treatment. However, there was no significant difference in prognosis between patients who refused to undergo radical cystectomy and those who underwent. In addition, rehospitalization rates for complications and additional treatment were significantly higher in patients who received conservative treatment (69.3% vs. 34.2%; p < 0.01), and the length of hospital stay was also prolonged compared to patients who received radical cystectomy (26 vs. 9 days; p = 0.03). CONCLUSIONS: Overall, conservative treatment had a significantly poorer prognosis than radical cystectomy, but there was no significant difference in prognosis when comparing patients who refused radical cystectomy and received conservative treatment with those who received radical cystectomy. However, hospitalization rates and length of stay were significantly worse for patients who chose conservative treatment, which may lead to a decline in quality of life.

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.

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.

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.

Serum CCL2 Is a Prognostic Biomarker for Non-Metastatic Castration-Sensitive Prostate Cancer.

Purpose: Prostate-specific antigen (PSA) is a useful prostate cancer (PC) biomarker, but some cases reported that PSA does not correlate with the Gleason score. Serum chemokine (CC motif) ligand 2 (CCL2) has been reported to be a potential complementary PSA biomarker, but it remains unclear whether it can be applied to non-metastatic castration-sensitive prostate cancer (nmCSPC) or each section of the stages. Serum CCL2's usefulness was investigated as a prognostic nmCSPC biomarker in this study. Methods: Serum samples were collected from 379 patients who underwent prostate biopsy at Kanazawa University Hospital from 2007 to 2013. A total of 230 patients with nmCSPC were included in this study of the 255 patients with histologically diagnosed prostate cancer. The serum CCL2 efficacy as a prognostic nmCSPC biomarker was investigated retrospectively. Results: An independent significant predictor of worse OS was CCL2 ≥ 280 pg/dL and CRP ≥ 0.5 mg/dL in multivariate analysis. Gleason score ≥ 8 and CCL2 ≥ 280 pg/dL were independent significant predictors of CRPC-free survival (CFS) worsening in multivariate analysis. Serum CCL2 was a predictive biomarker for OS and CFS in nmCSPC. Furthermore, CCL2 ≥ 280 pg/mL patients had significantly worse visceral metastasis-free survival than those with CCL2 < 280 pg/mL. Conclusion: This study is the first to demonstrate serum CCL2 utility as a biomarker to predict OS and CFS in nmCSPC.

Efficacy of Androgen Receptor-targeted Drugs After Prostate Cancer Recurrence With Bone Metastases: PROSTAT-BSI Sub-analysis.

BACKGROUND/AIM: This study aimed to evaluate the therapeutic benefit of novel androgen receptor-targeted agents (ARTAs) in castration-resistant prostate cancer (CRPC) with bone metastases in Japan. PATIENTS AND METHODS: In followup to our prospective observational study (PROSTAT-BSI) from 2012 to 2018 on metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic CRPC (mCRPC) before docetaxel initiation, we conducted this sub-analysis to investigate the benefit of ARTAs after clinical recurrence on overall survival (OS) in the real-world clinical setting in Japan. In this study, we compared patients who were treated with ARTA with those who received only vintage hormone therapy including docetaxel after clinical recurrence. RESULTS: In the mHSPC group, 69 patients became mCRPC and were treated with or without ARTAs. No significant difference was observed in prostate-specific antigen (PSA) progression-free survival between the ARTA (+) and ARTA (-) groups; however, OS after clinical recurrence was significantly better in the ARTA (+) group than in the ARTA (-) group (median OS 31.9 vs. 23.0 months; p<0.01). CONCLUSION: The ARTAs are beneficial even after mHSPC recurrence in Japanese patients in the real-world clinical setting. Since ARTAs are beneficial after clinical recurrence, it may be better to switch to ARTAs whenever necessary based on PSA response after combined androgen blockade therapy, considering the adverse effects and cost. This approach may be suitable to reduce overtreatment in Japanese patients with mHSPC.

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

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

Favorable Response of Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma with Only Small Lesions to not be Considered Measurable by RECIST.

PURPOSE: Pembrolizumab is currently considered the standard second-line treatment for advanced urothelial carcinoma (UC). This study aimed to investigate the efficacy and safety of pembrolizumab in patients with advanced UC in real-world data, which is not well-reported. MATERIALS AND METHODS: The study included 97 patients with advanced UC whose lesions were classified according to the Response Evaluation Criteria in Solid Tumors (RECIST). The median age was 73 years. Nineteen patients (20%) with performance status (PS) 2-4 were included. The percentages of liver, lung, bone, and lymph node metastasis were 18%, 27%, 19%, and 76%, respectively. The efficacy, safety, and risk factors for prognosis were evaluated for patients with and without measurable lesions. RESULTS: The best response was complete response in nine patients (9%) and partial response in 16 patients (17%). The median progression-free survival and overall survival were 3.7 months (95% confidence interval [CI]: 2.8-4.7) and 11.8 months (95% CI: 6.7-17.0), respectively. Twenty-one (22%) patients had no measurable lesions per RECIST. In univariate and multivariate analysis, PS 2-4 and lesions by RECIST were identified as factors associated with short overall survival (OS). The median OS of 18.3 months in patients without lesions by RECIST was significantly longer than the median OS of 6.7 months in patients with lesions by RECIST (p = .012). CONCLUSION: We demonstrated that good PS 0-1 and no measurable lesions, especially small lesions, by RECIST were favorable prognostic factors in patients with advanced UC treated by pembrolizumab.

Blood Cell Count Biomarkers Predicting Efficacy of Pembrolizumab as Second-line Therapy for Advanced Urothelial Carcinoma.

BACKGROUND/AIM: To investigate the blood markers for predicting pembrolizumab efficacy in advanced urothelial carcinoma (UC). PATIENTS AND METHODS: This study included 91 advanced UC patients. The relationship between prognosis and markers from peripheral blood cell counts, including the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), and systemic inflammation response index (SIRI=monocytes × neutrophils/lymphocytes), was evaluated. RESULTS: Multivariate analysis indicated that pretreatment NLR and the 1-month-change NLR were both significantly associated with overall survival (OS) after pembrolizumab initiation. When the patients were divided into four groups according to calculated cutoffs using Cox proportional hazard model, the pretreatment NLR <2.9 and 1-month change NLR <+43% groups had a significantly better OS than the pretreatment NLR ≥2.9 and 1-month-change NLR ≥+43% groups. CONCLUSION: NLR, MLR, PLR and SIRI before pembrolizumab and 1-month-change NLR in advanced UC correlated with OS after pembrolizumab treatment.

CD38, CD157, and RAGE as Molecular Determinants for Social Behavior.

Recent studies provide evidence to support that cluster of differentiation 38 (CD38) and CD157 meaningfully act in the brain as neuroregulators. They primarily affect social behaviors. Social behaviors are impaired in Cd38 and Cd157 knockout mice. Single-nucleotide polymorphisms of the CD38 and CD157/BST1 genes are associated with multiple neurological and psychiatric conditions, including autism spectrum disorder, Parkinson's disease, and schizophrenia. In addition, both antigens are related to infectious and immunoregulational processes. The most important clues to demonstrate how these molecules play a role in the brain are oxytocin (OT) and the OT system. OT is axo-dendritically secreted into the brain from OT-containing neurons and causes activation of OT receptors mainly on hypothalamic neurons. Here, we overview the CD38/CD157-dependent OT release mechanism as the initiation step for social behavior. The receptor for advanced glycation end-products (RAGE) is a newly identified molecule as an OT binding protein and serves as a transporter of OT to the brain, crossing over the blood-brain barrier, resulting in the regulation of brain OT levels. We point out new roles of CD38 and CD157 during neuronal development and aging in relation to nicotinamide adenine dinucleotide+ levels in embryonic and adult nervous systems. Finally, we discuss how CD38, CD157, and RAGE are crucial for social recognition and behavior in daily life.

Effectiveness of Synthetic Polymer-coated Peripherally Inserted Central Catheter in Patients With Advanced Cancer.

BACKGROUND/AIM: A peripherally inserted central catheter (PICC) is recommended for the safe administration of anticancer agents. The effectiveness of synthetic polymer-coated and non-coated PICCs was compared. PATIENTS AND METHODS: Patients with advanced cancers who had indwelling PICCs were reviewed using their medical records. Three types of PICCs were compared in terms of complications and catheter failure. RESULTS: A total of 90 patients were retrospectively analyzed, including 31 with Groshong PICCs, 30 with Argyle PICC kit, and 29 with Argyle PICC kit II. The incidence of catheter failure for Groshong PICC, Argyle PICC kit, and Argyle PICC kit II per 1,000 PICC days was 4.4614, 5.6617, and 0.8658, respectively. Catheter failure-free survival in the Argyle PICC kit II group was significantly better than that in the Argyle PICC kit group (p=0.0339). CONCLUSION: Argyle PICC kit II, a synthetic polymer-coated PICC, may render longer patency and prevention of catheter failure than non-coated PICCs.