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1.
Hinyokika Kiyo ; 69(8): 207-214, 2023 Aug.
Article in Japanese | MEDLINE | ID: mdl-37667597

ABSTRACT

We analyzed 45 patients who were diagnosed with renal cell carcinoma with inferior vena cava tumor thrombus (IVC) and underwent surgical resection at Nagasaki University Hospital during the 17 years from March 2003 to November 2020. The median overall survival (OS) was 68.5, 53.5, 45.7, and 20.4 months, respectively, according to the tumor thrombus level (Lv) of I, II, III and IV, with a median level of (P=0.025). In multivariate analysis, pathological sarcomatoid changes were associated with risk of tumor recurrence in the postoperative complete remission group, and IVC thrombus level above Lv III was associated with poor prognosis in the postoperative incomplete remission group. On postoperative systemic treatment for the postoperative recurrence group and the incomplete remission group, overall survival was significantly prolonged in cases using immune checkpoint inhibitors. The results of surgical treatment of renal cell carcinoma with IVC tumor embolization were analyzed. Patients who underwent surgical resection and achieved postoperative complete remission had a relatively long prognosis with a median OS of more than 6 years. In contrast, patients with metastases, especially those with postoperative incomplete remission group, had a poor prognosis despite surgical resection, depending on the patient's situation.


Subject(s)
Carcinoma, Renal Cell , Embolization, Therapeutic , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/surgery , Vena Cava, Inferior/surgery , Kidney Neoplasms/surgery
2.
Hinyokika Kiyo ; 69(2): 33-39, 2023 Feb.
Article in Japanese | MEDLINE | ID: mdl-36863869

ABSTRACT

Detection of post-transplant malignant tumors and the analysis of the associated risk factors is important for monitoring the progress after renal transplantation. In this study, we retrospectively examined the medical records of 298 patients who underwent renal transplantation at two facilities in Nagasaki Prefecture (Nagasaki University Hospital and National Hospital Organization Nagasaki Medical Center). Of the 298 patients, 45 (15.1%) patients had developed malignant tumors with 50 lesions. The most common type of malignant tumor was skin cancer (eight patients; 17.8%), followed by renal cancer (six patients; 13.3%), and pancreatic cancer and colorectal cancer, (four patients; 9.0% each). Five patients (11.1%) had multiple cancers, four of whom had skin cancer. The cumulative incidence within 10 and 20 years after renal transplantation was 6.0 and 17.9%, respectively. Univariate analysis identified age at transplantation and administration of cyclosporine and rituximab as risk factors, while multivariate analysis identified age at transplantation and administration of rituximab as independent factors. The administration of rituximab was associated with the development of malignant tumors. However, further investigation is required to establish the association with post-transplant malignant neoplasms.


Subject(s)
Kidney Neoplasms , Kidney Transplantation , Skin Neoplasms , Humans , Kidney Transplantation/adverse effects , Retrospective Studies , Rituximab
3.
BJU Int ; 129(4): 534-541, 2022 04.
Article in English | MEDLINE | ID: mdl-34383381

ABSTRACT

OBJECTIVES: To compare the urinary pH, recurrence-free survival (RFS), and safety of adjuvant intravesical therapy in patients with non-muscle-invasive bladder cancer (NMIBC) receiving mitomycin C (MMC) therapy and MMC + cytosine arabinoside (Ara-C) therapy. PATIENTS AND METHODS: A total of 165 patients with NMIBC from six hospitals were randomly allocated to two groups: weekly instillation of MMC + Ara-C (30 mg/30 mL + 200 mg/10 mL) for 6 weeks and the same instillation schedule of MMC (30 mg/40 mL). The primary outcome was RFS, and secondary outcomes were urinary pH and toxicity in the two groups. RESULTS: A total of 81 and 87 patients were randomised into the MMC and MMC + Ara-C groups, respectively. Overall, the RFS in the MMC + Ara-C group was significantly longer (P = 0.018) than that in the MMC group. A similar significant difference was detected in patients with intermediate-risk NMIBC, but not in those with high-risk NMIBC. The mean (SD) urinary pH was significantly higher in the MMC + Ara-C group than in the MMC group, at 6.56 (0.61) vs 5.78 (0.64) (P < 0.001), and the frequency of a urinary pH of >7.0 in the MMC and MMC + Ara-C groups was 6.3% and 26.7%, respectively (P < 0.001). Multivariate analysis models including clinicopathological features and second transurethral resection demonstrated that increased urinary pH was associated with better outcomes (hazard ratio 0.18, 95% confidential interval 0.18-0.038; P < 0.001). In all, there were 14 and 10 adverse events in the MMC and MMC + Ara-C groups, respectively, without a significant difference (P = 0.113). CONCLUSIONS: Our randomised clinical trial suggested that intravesical therapy with MMC and Ara-C is useful and safe for patients with intermediate-risk NMIBC. Increase in urinary pH with Ara-C is speculated as a mechanism for increased anti-cancer effects.


Subject(s)
Mitomycin , Urinary Bladder Neoplasms , Administration, Intravesical , Antibiotics, Antineoplastic/therapeutic use , Cytarabine/therapeutic use , Female , Humans , Male , Mitomycin/therapeutic use , Urinary Bladder Neoplasms/surgery
4.
Urol Int ; 106(6): 623-629, 2022.
Article in English | MEDLINE | ID: mdl-35045411

ABSTRACT

INTRODUCTION: We investigated the efficacy and safety of every-other-day dosing of sunitinib for the treatment of metastatic renal cell carcinoma (mRCC) with extended follow-up and the impact of immune checkpoint inhibitor (ICI) drugs. METHODS: Thirty-two patients received standard dosing treatment (standard group), and 32 received every-other-day treatment (experimental group). Efficacy endpoints included progression-free survival (PFS), overall survival (OS), and objective response rate. We also analyzed the clinical course of patients treated with nivolumab after sunitinib. RESULTS: The minimum follow-up was 42 months. Median PFS and OS were significantly longer in the experimental group compared with the standard group (27.6 vs. 6.2 and 87.1 vs. 24.6 months, respectively). The incidence of dose interruption of sunitinib caused by adverse events was significantly lower in the experimental group than in the standard group (28.1% vs. 56.3%, p = 0.042). Multivariate analysis showed that every-other-day dosing was a significant independent prognostic factor (p = 0.038), although nivolumab use was not (p = 0.232). Twelve patients were treated with nivolumab after sunitinib, and patients who did not respond to nivolumab tended to respond to pretreatment sunitinib for a long period. DISCUSSION/CONCLUSION: Long-term follow-up confirmed the efficacy and safety of every-other-day dosing of sunitinib for mRCC patients in the ICI era.


Subject(s)
Antineoplastic Agents , Carcinoma, Renal Cell , Kidney Neoplasms , Antineoplastic Agents/adverse effects , Carcinoma, Renal Cell/pathology , Disease-Free Survival , Follow-Up Studies , Humans , Kidney Neoplasms/pathology , Nivolumab/therapeutic use , Pyrroles/adverse effects , Retrospective Studies , Sunitinib/therapeutic use , Treatment Outcome
5.
Int J Urol ; 29(6): 587-594, 2022 06.
Article in English | MEDLINE | ID: mdl-35288997

ABSTRACT

OBJECTIVES: To investigate the prevalence of the clonal group Escherichia coli ST131 in urologic patients, and to clarify the mechanisms underlying the high prevalence of the antimicrobial resistant genes in ST131. METHODS: We used 65 Escherichia coli strains collected from the Department of Urology, Nagasaki University Hospital, between January 2018 and December 2018. All of them underwent multilocus sequence typing and were analyzed for genes associated with quinolone resistance and extended-spectrum ß-lactamases. To compare ST131 and non-ST131 strains, bacterial conjugation experiments and intestinal colonization evaluations were performed. RESULTS: ST131 was the most dominant among all the strains, along with levofloxacin resistant strains, and extended-spectrum ß-lactamases positive strains (32%, 63%, and 73%, respectively). 12 out of 15 extended-spectrum ß-lactamases-producing Escherichia coli strains harbored CTX-M-9. In particular, all extended-spectrum ß-lactamases-producing ST131 strains possessed CTX-M-9. The proportions of ST131 strains with or without quinolone resistance-determining region mutations were significantly higher and lower, respectively, than that of non-ST131 strains (P = 0.0002 and P < 0.0001, respectively). When Klebsiella pneumoniae was used as a donor, three ST131 strains acquired extended-spectrum ß-lactamases a total of 16 times (six, four, and six times each), which was significantly more than that in one of the non-ST131 strains (two times). The amount of bacteria was significantly lower in the ST131 strains than in the non-ST131 strains administered to mice. Both the ST131 and non-ST131 strains increased again after the administration of vancomycin, even after the colony was not detected. CONCLUSIONS: These results support the mechanisms underlying the prevalence of ST131 strains in hospitals, particularly in urologic patients.


Subject(s)
Escherichia coli Infections , Quinolones , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Escherichia coli/genetics , Escherichia coli Infections/drug therapy , Escherichia coli Infections/epidemiology , Escherichia coli Infections/microbiology , Humans , Mice , Plasmids/genetics , Quinolones/pharmacology , beta-Lactamases/genetics
6.
Medicina (Kaunas) ; 58(6)2022 Jun 19.
Article in English | MEDLINE | ID: mdl-35744088

ABSTRACT

Background and Objectives: To determine changes in the blood pressure (BP) and pulse rate (PR) before and after the administration of mirabegron in real-world clinical practice for patients with overactive bladder (OAB). Materials and Methods: This study was conducted in patients newly diagnosed with OAB. Before and 12 weeks after mirabegron treatment, we evaluated the effects on BP and PR. An overall examination was conducted, and the patients were divided into two groups according to their age: a young group (<65 years old) and an old group (≥65 years old). Results: A total of 263 patients were enrolled in this study. In the overall and intragroup comparisons, the systolic BP (SBP) did not change significantly after mirabegron administration. However, an increase in SBP of ≥10 mmHg was observed in 53 (20.2%), 4 (7.4%), and 49 (23.4%) in the entire group, young group, and old group, respectively (p = 0.009). Regarding diastolic BP, a significant decrease after the treatment was detected in entire (71.2 ± 11.4 versus 69.8 ± 10.7 mmHg; p = 0.041) and old patients (71.5 ± 10.6 versus 69.5 ± 10.2 mmHg; p = 0.012). There was no significant change in PR in our study population. Further examination using a propensity match score revealed that age was the risk factor for the increase in SBP after mirabegron administration. Conclusions: Mirabegron does not have any adverse effects on BP and PR. However, since some patients in this study had elevated SBP after administration, we suggest regular BP monitoring during mirabegron treatment.


Subject(s)
Urinary Bladder, Overactive , Urological Agents , Acetanilides/adverse effects , Aged , Blood Pressure , Heart Rate , Humans , Thiazoles , Treatment Outcome , Urinary Bladder, Overactive/diagnosis , Urinary Bladder, Overactive/drug therapy , Urological Agents/adverse effects
7.
Hinyokika Kiyo ; 68(12): 369-376, 2022 Dec.
Article in Japanese | MEDLINE | ID: mdl-36627770

ABSTRACT

Patients on chronic dialysis for end-stage renal disease (ESRD) show an increased incidence of renal cell carcinoma (RCC). We investigated the clinicopathological characteristics and outcomes of 54 patients who underwent nephrectomy for RCC due to ESRD between 1992 and 2019. The patients consisted of 44 men and 10 women, with a median age of 62.9 years. The median duration of dialysis before surgery was 12.9 years. The clinical stage of the 54 RCCs was stage I in 44, stage II in 1, stage III in 1, and stage IV in 8. With a median follow-up of 5.1 years after surgery, the 5-year cancer-specific and overall survival rates were 84.3 and 61.8%, respectively. Patients with symptomatic RCC had a longer period of dialysis, presented with larger tumors of higher grade and stage, and had worse prognosis compared with those with incidentally discovered RCC. Cox proportional hazards analysis performed with clinicopathological features and symptomatic/incidental detection showed that older age and symptomatic RCC were independently associated with worse overall survival. Our data show that early detection is important for a good prognosis.


Subject(s)
Carcinoma, Renal Cell , Kidney Failure, Chronic , Kidney Neoplasms , Male , Humans , Female , Middle Aged , Carcinoma, Renal Cell/surgery , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/surgery , Kidney Neoplasms/pathology , Renal Dialysis/adverse effects , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Prognosis , Nephrectomy/adverse effects , Retrospective Studies
8.
Prostate ; 81(15): 1252-1260, 2021 11.
Article in English | MEDLINE | ID: mdl-34492128

ABSTRACT

BACKGROUND: Large tumor suppressor 2 (LATS2) is an important regulator of the Hippo pathway and it plays crucial roles in cell survival and behaviors. Herein, we evaluated the pathological roles of LATS2 in prostate cancer (PC), for which very little information is available. METHODS: Cell proliferation, migration, and invasion in response to the siRNA-mediated knockdown (KD) LATS2 expression were evaluated in two PC cell lines (LNCaP and PC3). The expression of LATS2 in specimens from 204 PC patients was investigated immunohistochemically, and the relationships between its expression and clinicopathological features, proliferation index (PI; measured using an anti-KI-67 antibody), and biochemical recurrence (BCR) were investigated. RESULTS: KD of LATS2 increased the growth, migration, and invasion in LNCaP cells and only increased migration in PC3 cells. The expression of LATS2 was negatively associated with the grade group, T, N, M stage, and PI. In addition, the expression of LATS2 was a useful predictor of the histological effects of neoadjuvant hormonal therapy and BCR-free survival periods. A multivariate analysis model including clinicopathological features showed that negative expression of LATS2 had a significantly higher risk of BCR (odds ratio = 2.95, P < 0.001). CONCLUSIONS: LATS2 acts as a tumor suppressor in PC. LATS2 expression is a useful predictor for BCR. LATS2-related activities are possibly dependent on the androgen-dependency of PC cells. Therefore, we suggest that LATS2 could be a potential therapeutic target and a useful predictor for outcome in patients with PC.


Subject(s)
Cell Proliferation/physiology , Gene Expression Regulation, Neoplastic , Prostatic Neoplasms/metabolism , Protein Serine-Threonine Kinases/metabolism , Tumor Suppressor Proteins/metabolism , Cell Line, Tumor , Cell Movement/physiology , Humans , Male , Prognosis , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Protein Serine-Threonine Kinases/genetics , RNA, Small Interfering , Tumor Suppressor Proteins/genetics
9.
Can J Urol ; 28(3): 10706-10712, 2021 06.
Article in English | MEDLINE | ID: mdl-34129467

ABSTRACT

INTRODUCTION: To clarify the efficacy and safety of propiverine hydrochloride for incontinence after robot-assisted laparoscopic prostatectomy (RALP)/laparoscopic radical prostatectomy (LRP), along with changes in the urethral pressure profile (UPP) and quality of life in patients treated with propiverine hydrochloride. MATERIALS AND METHODS: In this randomized, comparative study, 104 patients who were aware of urinary incontinence after RALP or LRP were assigned to receive propiverine hydrochloride (treatment group) or not (controls). Pad test results, International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) scores, and UPP results [including maximum urethral closure pressure (MUCP) and functional urethral length (FUL)], were recorded immediately and at 6 months postoperatively. RESULTS: No serious intraoperative complications or adverse events were caused by propiverine hydrochloride. The pad-test negative rate was significantly greater in the treatment group than in controls (89.1% vs. 73.2%, p = 0.044). Changes in ICIQ-SF scores and MUCP were significantly greater in the treatment group than in controls [-6.5 vs. -4.5 points (p = 0.021), and +49.5 vs. +28.7 mmHg (p = 0.038), respectively]. FUL change did not significantly differ between groups [+4.5 vs. +3.8 mm (p = 0.091)]. In univariate logistic regression analyses, body mass index (BMI), MUCP, and treatment with propiverine hydrochloride were significantly associated with continence status. In multivariate analyses, BMI and MUCP were independently associated with continence status [odds ratio (OR), 1.266; 95% confidence interval (CI), 1.047-1.530 (p = 0.015), and OR, 0.986; 95% CI, 0.973-0.999 (p = 0.042), respectively]. CONCLUSIONS: Treatment with propiverine hydrochloride alleviated urinary incontinence while improving patient symptoms and quality of life after RALP or LRP.


Subject(s)
Benzilates , Prostatectomy , Urinary Incontinence , Benzilates/adverse effects , Humans , Laparoscopy , Male , Prostatectomy/adverse effects , Prostatectomy/methods , Prostatic Neoplasms/surgery , Quality of Life , Robotics , Urinary Incontinence/drug therapy , Urinary Incontinence/etiology
10.
Acta Med Okayama ; 75(5): 663-667, 2021.
Article in English | MEDLINE | ID: mdl-34703052

ABSTRACT

The aim of this report is to introduce an on-going, multicenter, randomized controlled trial to evaluate whether tailored antimicrobial prophylaxis guided by rectal culture screening prevents acute bacterial prostatitis following transrectal prostate biopsy (TRPB). Patients will be randomized into an intervention or non-intervention group; tazobactam-piperacillin or levofloxacin will be prophylactically administered according to the results of rectal culture prior to TRPB in the intervention group whereas levofloxacin will be routinely given in the non-intervention group. The primary endpoint is the occurrence rate of acute bacterial prostatitis after TRPB. Recruitment begins in April, 2021 and the target total sample size is 5,100 participants.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacterial Infections/microbiology , Multicenter Studies as Topic , Prostatic Diseases/microbiology , Randomized Controlled Trials as Topic , Bacterial Infections/diagnosis , Bacterial Infections/drug therapy , Humans , Male , Prostatic Diseases/drug therapy , Prostatic Diseases/pathology
11.
Int J Urol ; 28(4): 397-403, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33377223

ABSTRACT

OBJECTIVE: To assess the relationship between visceral fat accumulation and lower urinary tract symptoms in female patients. METHODS: In this single-center study, we enrolled all women who underwent screening abdominal computed tomography 3 months before the study, irrespective of whether they experienced lower urinary tract symptoms. The Overactive Bladder Symptom Score was used to assess subjective symptoms. Uroflowmetry and ultrasound assessment of post-void residual urine were carried out to assess objective signs. We analyzed the relationship between lower urinary tract symptoms and various body fat accumulation parameters, including visceral fat area, visceral fat volume and total abdominal fat volume, assessed using computed tomography scans. RESULTS: A total of 182 patients were divided into the overactive bladder (n = 71, 39.0%) and the non-overactive bladder (n = 111, 61.0%) groups. The visceral fat area, visceral fat volume and visceral fat volume/total abdominal fat volume values were all significantly higher in the overactive bladder group than in the non-overactive bladder group (P < 0.001). Of these parameters, the visceral fat volume/total abdominal fat volume ratio showed the strongest correlation with the total Overactive Bladder Symptom Score (r = 0.394, P < 0.001). The maximum urine flow rate correlated negatively with the visceral fat volume/total abdominal fat volume value (visceral fat volume/total abdominal fat volume r = -0.289, P < 0.001). Subsequent multivariate analysis showed that a high visceral fat volume/total abdominal fat volume value, age and metabolic syndrome-related diseases were independent risk factors for the presence of overactive bladder. CONCLUSIONS: Excessive accumulation of visceral fat is independently associated with overactive bladder in females.


Subject(s)
Lower Urinary Tract Symptoms , Urinary Bladder, Overactive , Female , Humans , Intra-Abdominal Fat/diagnostic imaging , Ultrasonography , Urinary Bladder, Overactive/diagnostic imaging , Urologic Surgical Procedures
12.
Molecules ; 26(2)2021 Jan 16.
Article in English | MEDLINE | ID: mdl-33467066

ABSTRACT

Benign prostatic hyperplasia (BPH) is arguably the most common benign disease among men. This disease is often associated with lower urinary tract symptoms (LUTS) in men and significantly decreases the quality of life. Polyphenol consumption reportedly plays an important role in the prevention of many diseases, including BPH. In recent years, in addition to disease prevention, many studies have reported the efficacy and safety of polyphenol treatment against various pathological conditions in vivo and in vitro. Furthermore, numerous studies have also revealed the molecular mechanisms of the antioxidant and anti-inflammatory effects of polyphenols. We believe that an improved understanding of the detailed pharmacological roles of polyphenol-induced activities at a molecular level is important for the prevention and treatment of BPH. Polyphenols are composed of many members, and their biological roles differ. In this review, we first provide information regarding the pathological roles of oxidative stress and inflammation in BPH. Next, the antioxidant and anti-inflammatory effects of polyphenols, including those of flavonoids and non-flavonoids, are discussed. Finally, we talk about the results and limitations of previous clinical trials that have used polyphenols in BPH, with particular focus on their molecular mechanisms of action.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antioxidants/therapeutic use , Polyphenols/therapeutic use , Prostatic Hyperplasia/drug therapy , Humans , Lower Urinary Tract Symptoms/drug therapy , Male , Quality of Life
13.
Int J Clin Oncol ; 25(6): 1163-1169, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32125546

ABSTRACT

BACKGROUND: A previous comparative study in Japan has demonstrated that the two consecutive UroVysion tests are useful tools to detect the presence of bladder cancer during follow-up after transurethral resection, but they also presented their high rates of false-positive results. Here, we aimed to evaluate the relationship between the UroVysion tests and subsequent intravesical recurrence. METHODS: In the previous study, patients without bladder cancer during the first analysis showed the same examination set repeated 3 months later as the second analysis. In this follow-up study, 326 patients showed negative findings confirmed on cystoscopy during the second UroVysion test. Recurrence-free survival was assessed using a median follow-up of 27 months. RESULTS: In the two consecutive UroVysion tests, 214 patients (65.6%) showed negative UroVysion results in both tests, whereas 91 presented a positive result on either tests and 21 patients presented positive results in both tests. During the follow-up, 40 patients (12.3%) had an intravesical recurrence with non-muscle-invasive bladder cancer. The recurrence rates in patients with negative results in both tests, those with one positive result in either tests, and those with positive results in both tests were 8.4%, 16.5%, and 33.3%, respectively. The multivariate analysis indicated that the history of bladder cancer and the consecutive UroVysion test pattern were independent risk factors for recurrence. CONCLUSIONS: Our data confirmed the effectiveness of two consecutive UroVysion tests in predicting intravesical recurrence after TURBT. Further prospective studies would help determine an appropriate interval for cystoscopy follow-up.


Subject(s)
In Situ Hybridization, Fluorescence/methods , Neoplasm Recurrence, Local/diagnosis , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Cystectomy , Cystoscopy , Female , Follow-Up Studies , Humans , Japan , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Prospective Studies , Urinary Bladder Neoplasms/mortality
14.
Molecules ; 25(22)2020 Nov 11.
Article in English | MEDLINE | ID: mdl-33187225

ABSTRACT

Oxidative stress plays an important role in cellular processes. Consequently, oxidative stress also affects etiology, progression, and response to therapeutics in various pathological conditions including malignant tumors. Oxidative stress and associated outcomes are often brought about by excessive generation of reactive oxygen species (ROS). Accumulation of ROS occurs due to dysregulation of homeostasis in an otherwise strictly controlled physiological condition. In fact, intracellular ROS levels are closely associated with the pathological status and outcome of numerous diseases. Notably, mitochondria are recognized as the critical regulator and primary source of ROS. Damage to mitochondria increases mitochondrial ROS (mROS) production, which leads to an increased level of total intracellular ROS. However, intracellular ROS level may not always reflect mROS levels, as ROS is not only produced by mitochondria but also by other organelles such as endoplasmic reticulum and peroxisomes. Thus, an evaluation of mROS would help us to recognize the biological and pathological characteristics and predictive markers of malignant tumors and develop efficient treatment strategies. In this review, we describe the pathological significance of mROS in malignant neoplasms. In particular, we show the association of mROS-related signaling in the molecular mechanisms of chemically synthesized and natural chemotherapeutic agents and photodynamic therapy.


Subject(s)
Biological Products/pharmacology , Mitochondria/metabolism , Photosensitizing Agents/pharmacology , Reactive Oxygen Species/metabolism , Amaryllidaceae Alkaloids/pharmacology , Animals , Antineoplastic Agents/pharmacology , Antioxidants/chemistry , Ascorbic Acid/pharmacology , Cell Line, Tumor , Curcumin/pharmacology , Endoplasmic Reticulum/metabolism , Homeostasis/drug effects , Humans , Isoquinolines/pharmacology , Oxidative Stress , Paclitaxel/pharmacology , Peroxisomes/metabolism , Photochemotherapy , Signal Transduction/drug effects , TNF-Related Apoptosis-Inducing Ligand/metabolism , Tannins/pharmacology , Taxoids/pharmacology , Triterpenes/pharmacology
15.
Molecules ; 25(3)2020 Jan 29.
Article in English | MEDLINE | ID: mdl-32013065

ABSTRACT

Bladder cancer (BC) is a representative of urological cancer with a high recurrence and metastasis potential. Currently, cisplatin-based chemotherapy and immune checkpoint inhibitors are used as standard therapy in patients with advanced/metastatic BC. However, these therapies often show severe adverse events, and prolongation of survival is unsatisfactory. Therefore, a treatment strategy using natural compounds is of great interest. In this review, we focused on the anti-cancer effects of isothiocyanates (ITCs) derived from cruciferous vegetables, which are widely cultivated and consumed in many regions worldwide. Specifically, we discuss the anti-cancer effects of four ITC compounds-allyl isothiocyanate, benzyl isothiocyanate, sulforaphane, and phenethyl isothiocyanate-in BC; the molecular mechanisms underlying their anti-cancer effects; current trends and future direction of ITC-based treatment strategies; and the carcinogenic potential of ITCs. We also discuss the advantages and limitations of each ITC in BC treatment, furthering the consideration of ITCs in treatment strategies and for improving the prognosis of patients with BC.


Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Brassicaceae/chemistry , Isothiocyanates/therapeutic use , Urinary Bladder Neoplasms/drug therapy , Animals , Antineoplastic Agents, Phytogenic/adverse effects , Carcinogens/pharmacology , Humans , Isothiocyanates/adverse effects , Isothiocyanates/isolation & purification , Neoplasm Metastasis/drug therapy , Vegetables/chemistry
16.
Hinyokika Kiyo ; 66(4): 107-113, 2020 Apr.
Article in Japanese | MEDLINE | ID: mdl-32483944

ABSTRACT

Chemotherapy and immune-checkpoint inhibitors, used as second-line treatments for advanced urothelial cancer (UC), can have adverse effects in some patients, such as decreased organ function. We investigated the effectiveness of cooperation with medical/welfare services, so-called cooperative medicine, in these cases. A total of 137 UC patients who had undergone second-line therapy were analyzed. Of these 137 patients, 49 were categorized in the "cooperative"treatment group, in which a general practitioner performed blood tests and transfusions ; and, administered medication, while nurses and case workers from a community health care institution provided mental and social support. There were 50 in the "joint" treatment group, who were treated jointly by a urologist and general practitioner ; and, 38 in the "solo" treatment group who were treated by a urologist only. The Short Form Health Survey, SF-36, was used to evaluate quality of life (QoL). We observed that the overall survival after the second-line treatment was significantly longer in the cooperative group than in the other two groups, with multivariate analyses confirming cooperative treatment as a significant factor for better prognosis (P=0.005). The period of second-line treatment in the cooperative group was significantly longer (P=0.003) than that in the solo group, whereas the proportion of patients who subsequently received third-line treatment was higher in the cooperative group, 58. 5%, than in the solo and joint groups, 26. 5% and 25. 5%, respectively. Posttreatment QoL measurements in the joint and solo groups were significantly lower for 3 and 6 items, respectively, whereas there was no appreciable decrease in post-treatment QoL measurements in the cooperative group. Multivariate analysis showed that cooperative treatment was particularly beneficial for female patients ≥75 years of age, and patients with status 2 performance.


Subject(s)
Carcinoma, Transitional Cell/drug therapy , Urologic Neoplasms/drug therapy , Antineoplastic Combined Chemotherapy Protocols , Female , Humans , Prognosis , Quality of Life
17.
Glycoconj J ; 36(5): 409-418, 2019 10.
Article in English | MEDLINE | ID: mdl-31243630

ABSTRACT

Stage-specific embryonic antigen-4 (SSEA-4), a specific marker for pluripotent stem cells, plays an important role in the malignant behavior of several cancers. Here, SSEA-4 expression was evaluated by immunohistochemistry using monoclonal antibody RM1 specific to SSEA-4 in 181 and 117 prostate cancer (PC) specimens obtained by biopsy and radical prostatectomy (RP), respectively. The relationships between SSEA-4 expression in cancer cells or the presence of SSEA-4-positive tumor-infiltrating immune cells (TICs) and clinicopathological parameters were analyzed. SSEA-4 expression in cancer cells was significantly associated with Gleason score, local progression, and lymph node and distant metastasis. In RP specimens, high SSEA-4 expression in cancer cells and the presence of SSEA-4-positive TICs were significant predictors of pT3, i.e., invasion and worse biochemical recurrence (BCR) after RP, respectively, in univariate analysis. In contrast, combination of high SSEA-4 expression in cancer cells and the presence of SSEA-4-positive TICs was an independent predictor for pT3 and BCR in multivariate analysis. Biologically this combination was also independently associated with suppression of apoptosis. Thus, the co-expression of SSEA-4 in cancer cells and TICs may have crucial roles in the malignant aggressiveness and prognosis of PC. Invasive potential and suppression of apoptosis may be linked to SSEA-4 expression.


Subject(s)
Biomarkers, Tumor/metabolism , Glycosphingolipids/metabolism , Lymphocytes, Tumor-Infiltrating/metabolism , Prostatic Neoplasms/diagnosis , Stage-Specific Embryonic Antigens/metabolism , Aged , Apoptosis , Biopsy , Humans , Lymph Nodes/metabolism , Lymph Nodes/pathology , Lymphatic Metastasis , Lymphocytes, Tumor-Infiltrating/pathology , Male , Middle Aged , Multivariate Analysis , Neoplasm Grading , Neoplasm Invasiveness , Neoplasm Staging , Prognosis , Prostatectomy , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/mortality , Prostatic Neoplasms/surgery , Survival Analysis
18.
Neurourol Urodyn ; 38(3): 927-933, 2019 03.
Article in English | MEDLINE | ID: mdl-30706965

ABSTRACT

AIMS: To assess the efficacy of salt reduction for improving nocturia in patients with high salt intake. METHODS: Changes in lower urinary symptoms and frequency volume chart by salt intake (men: 8 g/day; women: ≥7 g/day) were analyzed in this prospective study. Patients were instructed to use a brochure for salt intake restriction via interview once every four weeks. The daily salt intake was estimated by using spot urine samples. RESULTS: Two-hundred twenty-three (69.5%) patients were successful in reducing their daily salt intake (S group), whereas 98 (30.5%) patients failed to reduce their salt intake (F group). In the S group, nocturia improved from 2.3 ± 0.9 to 1.4 ± 1.0, and nocturnal polyuria index (NPi) improved from 30.2 ± 7.5 to 27.7 ± 7.3% (P < 0.001). In the Core Lower Urinary Tract Symptom Score (CLSS) of the S group, Q3 (urgency) improved from 1.0 ± 1.0 to 0.9 ± 1.0 (P = 0.001); Q1 (diurnal frequency) (P < 0.001), and Q2 (nocturia) also improved (P < 0.001). Moreover, the quality of life parameter improved significantly (P < 0.001). The patients in the F group did not have improvements in any symptom during the study period. CONCLUSIONS: Patients with nocturia who also have high salt intake should be advised to reduce their salt intake, as a lifestyle modification. Our results support the importance of randomized clinical trials with larger populations and the appropriate inclusion/exclusion criteria to conclude the clinical usefulness of salt reduction in this patient cohort.


Subject(s)
Diet, Sodium-Restricted , Nocturia/diet therapy , Nocturia/etiology , Sodium Chloride, Dietary/adverse effects , Adult , Aged , Aged, 80 and over , Circadian Rhythm , Cohort Studies , Female , Humans , Lower Urinary Tract Symptoms/diet therapy , Male , Middle Aged , Prospective Studies , Treatment Outcome , Urination , Urodynamics
19.
BMC Urol ; 19(1): 56, 2019 Jun 24.
Article in English | MEDLINE | ID: mdl-31234817

ABSTRACT

BACKGROUND: Transurethral resection (TUR) is the standard operation used for non-muscle invasive bladder cancer (NMIBC). Although most solid tumors are principally removed via single block resection without incising the mass, disruption of the lesion is unavoidable in traditional TUR. Furthermore, pathological diagnosis is often difficult due to heat-related denaturation of tissues in TUR. Although transurethral en-bloc resection is useful for judging tumor invasion, it is associated with a prolonged operative duration. We attempted to show the safety and usefulness of combined endoscopic mucosal resection (EMR) and en-bloc resection in NMIBC patients. METHODS: We investigated 39 patients with clinical NMIBC who were treated using our original EMR + en-bloc resection technique, which involved removal of the tumor mass that protruded from the mucosa, using a polypectomy snare similar to that used for EMR. The residual lesion was removed using en-bloc resection. The operative period, duration of hospitalization, and recurrence rates were compared with those of conventional TUR (n = 31). RESULTS: The mean (standard deviation, range) time interval for EMR and total operative duration were 1.6 (1.1, 1-5) min and 18.3 (10.5, 3-48) min, respectively. The total operative duration was comparable to that of TUR (17.3 min, p = 0.691). The mean duration of catheterization in the EMR + en-bloc resection group (4.2 days) was also similar to that in the TUR group (3.7 days; p = 0.285). No severe complications were observed with EMR + en-bloc resection. The pathologists were able to determine tumor invasiveness with considerable certainty in all specimens obtained via the EMR + en-bloc procedure than via TUR, and the difference in the ease of diagnosis was statistically significant (p = 0.016). Recurrence rates were comparable (p = 0.662) between the EMR + en-bloc (15.4%) and TUR groups (19.4%). CONCLUSIONS: Our results demonstrated that the EMR + en-bloc resection technique is feasible, safe, and useful for treating patients with NMIBC. Furthermore, this technique helps provide a more accurate pathological diagnosis.


Subject(s)
Endoscopic Mucosal Resection/methods , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/surgery , Urologic Surgical Procedures/methods , Combined Modality Therapy/methods , Combined Modality Therapy/standards , Endoscopic Mucosal Resection/standards , Female , Follow-Up Studies , Humans , Male , Neoplasm Invasiveness/pathology , Pilot Projects , Urologic Surgical Procedures/standards
20.
Int J Mol Sci ; 20(14)2019 Jul 11.
Article in English | MEDLINE | ID: mdl-31336777

ABSTRACT

Chronic kidney disease (CKD) is recognized as an irreversible reduction of functional nephrons and leads to an increased risk of various pathological conditions, including cardiovascular disease and neurological disorders, such as coronary artery calcification, hypertension, and stroke. In addition, CKD patients have impaired immunity against bacteria and viruses. Conversely, kidney transplantation (KT) is performed for patients with end-stage renal disease as a renal replacement therapy. Although kidney function is almost normalized by KT, immunosuppressive therapy is essential to maintain kidney allograft function and to prevent rejection. However, these patients are more susceptible to infection due to the immunosuppressive therapy required to maintain kidney allograft function. Thus, both CKD and KT present disadvantages in terms of suppression of immune function. Periodontal disease is defined as a chronic infection and inflammation of oral and periodontal tissues. Periodontal disease is characterized by the destruction of connective tissues of the periodontium and alveolar bone, which may lead to not only local symptoms but also systemic diseases, such as cardiovascular diseases, diabetes, liver disease, chronic obstructive pulmonary disease, and several types of cancer. In addition, the prevalence and severity of periodontal disease are significantly associated with mortality. Many researchers pay special attention to the pathological roles and clinical impact of periodontal disease in patients with CKD or KT. In this review, we provide information regarding important modulators of periodontal disease to better understand the relationship between periodontal disease and CKD and/or KT. Furthermore; we evaluate the impact of periodontal disease on various pathological conditions in patients with CKD and KT. Moreover, pathogens of periodontal disease common to CKD and KT are also discussed. Finally, we examine the importance of periodontal care in these patients. Thus, this review provides a comprehensive overview of the pathological roles and clinical significance of periodontal disease in patients with CKD and KT.


Subject(s)
Kidney Transplantation/adverse effects , Periodontal Diseases/etiology , Renal Insufficiency, Chronic/complications , Biomarkers , Comorbidity , Disease Susceptibility , Humans , Immunosuppression Therapy/adverse effects , Immunosuppression Therapy/methods , Kidney Transplantation/methods , Oxidative Stress , Periodontal Diseases/metabolism , Periodontal Diseases/pathology , Renal Insufficiency, Chronic/therapy
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