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In this study, we investigated a solid-phase dispersive extraction (SPDE) method and solid-phase derivatization method using the same solid-phase gel to extract methamphetamine (MA) from urine samples more efficiently and perform trifluoroacetic acid (TFA) derivatization for MA analysis by gas chromatography/mass spectrometry (GC/MS). N-Methylbenzylamine (NMe-BA) was added to the urine sample as a surrogate, and MA was extracted by SPDE using Oasis ® HLB gel as a solid-phase agent. After drying the solid-phase gel of the SPDE, anhydrous TFA was added to the MA-absorbed HLB gel in order to derivatize MA with TFA on the solid-phase, followed by elution of the TFA derivative from this gel using ethyl acetate. As a validation of the analytical method, the limit of detection (S/N = 3) and the limit of quantification (S/N > 10) of MA were 0.002 µg/mL and 0.01 µg/mL, respectively. And the average recovery rate was 97.6-100.1%, repeatability was 5.6-10.7%, and intermediate precision was 10.1-11.4% for low (0.02 µg/mL), intermediate (0.1 µg/mL), and high (1 µg/mL) concentrations of MA added in urine. The developed pretreatment method enabled continuous extraction, cleanup, and TFA derivatization of urinary MA on the same solid-phase. Thus, urinary MA can be analyzed easily, rapidly, and with high sensitivity and accuracy., (© 2024. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

Introduction: The prevalence of smoking, including heated tobacco products (HTPs), among Japanese dentists was reported to be 16.5%, significantly higher than that among Japanese physicians and United States dentists. However, large-scale studies on smoking cessation implementation based on dentists' smoking status and perceptions since the introduction of HTPs are lacking. Therefore, we aimed to investigate and assess dentists' attitudes toward smoking, including HTP use and smoking cessation, according to smoking status., Methods: A self-administered questionnaire comprising six major items was mailed to 3883 dentists who were members of the Aichi Dental Association in August 2019. The primary outcome was smoking cessation status. The secondary outcome was the impact of smoking on intervention for smoking cessation. This study was reported using the Strengthening the Reporting of Observational Studies in Epidemiology guidelines., Results: Among the 1317 (42%) dentists analyzed, men were more positive toward smoking than women. Current and former smokers were more positive about smoking than never smokers/users, regardless of the tobacco product type. Additionally, the current smoker group using conventional cigarettes was less likely to ask for their patients' smoking status than the never smoker group. Furthermore, the current smoker (OR=2.0; 95% CI: 1.3-3.1 vs never smoker) and HTP user (OR=1.9; 95% CI: 1.2-3.1 vs never user) groups were less likely to engage in smoking cessation than the never smoker/user groups, regardless of the tobacco product type., Conclusions: Since the smoking status of dentists affects the implementation of smoking cessation interventions, it is crucial to encourage them to quit using all tobacco products to promote smoking cessation interventions in dental practice. Additionally, providing proper smoking prevention education to dentists is an important task., Competing Interests: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none was reported., (© 2024 Oya-Watanabe Y. et al.)

The awareness of healthcare practitioners concerning heated tobacco product (HTP) use risks has been evaluated; however, few studies have investigated general dental practitioners’ awareness regarding HTP-use risks. In this cross-sectional study, we investigated dentists’ awareness of the risks of smoking, particularly HTP use. A self-administered questionnaire, including eight questions on conventional cigarette and HTP smoking/using status and both knowledge and awareness of HTP-use risks, was posted to 3883 dentists belonging to the Aichi Dental Association, Japan, in August 2019. Statistical analysis was performed using the Statistical Package for Social Sciences; statistical significance was set at p < 0.05. We analyzed the data of 1317 dentists (participation rate, 41.6%). The study group included cigarette smokers (11.5%) and HTP users (8.5%), among whom 41.1% were dual users. HTP users were more likely than never smokers/users to correctly perceive HTP-use risks (p < 0.05). This study indicates that in Japan, the proportion of HTP users is higher than that of the general population. It is important to educate not only smokers/users but also never smokers/users on the risks of smoking and using HTPs. Smoking cessation, including ceasing HTP use, and aiming to quit smoking and HTP use among dentists would contribute to appropriate smoking cessation among patients., Competing Interests: The authors declare no conflicts of interest.

Purpose: To evaluate the efficacy and safety of imidafenacin (IM), a novel short half-life anticholinergic, as add-on therapy for male LUTS with nocturia and nocturnal polyuria., Materials and Methods: This multicenter, prospective, randomized, open-labelled study was conducted and involved men who had frequency, urgency, and nocturia despite receiving a stable dose of α1-blocker for ≥1 month. Subjects were randomised to control (α1-blocker alone), IM twice/day (α1-blocker +0.1 mg imidafenacin twice daily), or IM nightly (α1-blocker plus 0.1 mg imidafenacin nightly) group; the treatment period was 8 weeks. Primary endpoints included improvements in night-time frequency and Nocturia Quality of Life Questionnaire (N-QOL) scores. Secondary endpoints included changes from the baseline in frequency volume chart variables, and post-void residual volume., Results and Limitations: Compared with the controls, IM twice/day and IM nightly patients had a significantly lower night-time frequency (changes from baseline: 0.1 ± 0.8 in control, -0.6 ± 0.9 in IM twice/day, and -0.4 ± 1.0 in IM nightly, p = 0.5227, 0.0006 and 0.0143, respectively). The hours of undisturbed sleep and N-QOL score were significantly improved in IM twice/day group, though not IM nightly group. Nocturnal urine volume was significantly reduced in IM nightly group, although total urine volume remained unchanged., Conclusions: A short half-life anticholinergic is suggested to be safe and effective as an add-on therapy for residual nocturia in patients with male LUTS receiving α1-blocker treatment. Anticholinergic administration nightly could reduce the nocturnal urine volume.

A total of 121 Japanese patients scheduled for prostate biopsy were randomly and double-blindly assigned to be given a single oral dose of 100 mg Tramadol mixed with 20 ml of sugar syrup or placebo, 30 minutes before the procedure. Pain severity was measured by verbal rating scale (VRS) and visual analog scales (VAS). We also analyzed cardio-respiratory parameters and complications. Of 121 patients, 117 replied validly to VRS and VAS ; and 91 of 117 patients replied to the cohort questionnaire for analysis of the late disorder, patient's impression, prolonged pain and past history of hemorrhoid treatment. Tramadol showed no significant effect on pain severity indicated by VRS and VAS, and no change in cardiorespiratory parameters. Furthermore, 70 patients without a history of hemorrhoid treatment, showed no significant analgesic benefits of Tramadol during the biopsy. In total, 3 patients had side effects of vomiting (CTCAE : grade 1)6), which subsided spontaneously. The oral administration of a single dose of 100 mg Tramadol 30 minutes before a transrectal needle biopsy of the prostate was safe, but was not effective to calm down the pain severity.

A case of neuroendocrine (NE) differentiated prostate cancer is reported herein, which was progressed with NE differentiation during hormonal treatment in adenocarcinoma of the prostate. A 65-year-old man was admitted to our department with increased serum prostate specific antigen (PSA) (150 ng/ml). A prostate biopsy was performed and histological examinations indicated poorly differentiated adenocarcinoma with a Gleason score of 5 + 4 = 9. Further examinations showed metastases to systemic bones. The clinical stage was T3bN0M1b and hormonal therapy using leuprorelin was started. Eighteen months after hormonal therapy, the serum PSA level declined to 1.702 ng/ml. He subsequently experienced edema in his legs. Computed tomography (CT) demonstrated enlargement of the prostate and swelling of multiple pelvic lymph nodes. Immunohistochemical examination of a re-biopsy specimen revealed a neuroendocrine carcinoma. The neuron-specific enolase (NSE) level was 50.9 ng/ml. The treatment measure was changed from hormonal therapy to combination chemotherapy comprising cisplatin (CDDP) and irinotecan (CPT-11). Pelvic radiotherapy (50 Gy) was then performed. Two courses of the chemotherapy resulted in a great reduction of the tumor volume. However, he had liver metastases 3 months later. His condition worsened rapidly and he died at 8 months after definite diagnosis.

A 69-year-old female presented with hypertension and a solid mass in the bladder on ultrasonography. Cystoscopy revealed a submucosal tumor in the right lateral wall of the bladder. A transurethral resection was performed. Histologically, pathologic examination revealed a malignant pheochromocytoma. She refused surgical therapy and radiation therapy. She had no treatment for two years. She suddenly complained of gross hematuria. T2-weighted magnetic resonance imaging showed a bladder tumor of high intensity and extra-bladder invasion. She was treated with chemotherapy (CVD) for 26 cycles. Since the tumor size was reduced, she was referred to our hospital for operative indication. Partial cystectomy was performed. Histologically, the tumor was a pheochromocytoma of the urinary bladder. Ten months after the operation, she has no clinical evidence of recurrence.

Objectives: We tested the usefulness of balloon-occluded arterial infusion (BOAI) of anticancer agent (cisplatin/gemcitabine), concomitant with hemodialysis, which delivers an extremely high concentration of anticancer agent to the site of a tumor without systemic adverse effects, along with concurrent radiation [Osaka-Medical College (OMC)-regimen] in patients with locally advanced bladder cancer. The results were compared with those of cystectomy., Methods: One hundred twenty-four patients were assigned to receive cystectomy (Gp1, n = 62) or OMC-regimen (Gp2, n = 62). In Gp2, patients besides undergoing complete response subsequently received secondary-BOAI with gemcitabine (1600 mg)., Results: In Gp1, 27 of 62 patients (43.5%) suffered disease recurrence, and more than half died within 1 year; the remainder died thereafter. The overall 5-, 10-, and 15-year survival rates were 53.8%, 46.0%, and 40.0%, respectively. In contrast, in Gp2, >70% of patients (44 of 62), especially >95% of patients with locally invasive tumors achieved complete response with no evidence of recurrent disease or metastasis after a mean follow-up of 163 (range, 32-736) weeks. At 14 years, overall survival was significantly improved at 79.7% (P = 0.015 vs. Gp1). Moreover, salvage therapy for secondary-BOAI with gemcitabine was effective in all 3 patients with T4 tumors or lymph node involvement, who showed stable disease (SD) after primary therapy with CDDP. No patients suffered Grade III or more severe toxicities., Conclusion: OMC-regimen, a new strategy for patients with locally-invasive bladder cancer, can be curative not only in patients for whom cystectomy is indicated, but also in patients whose condition is not amenable to curative treatment and for whom merely palliative treatment would otherwise seem the only option.

Stimulatory therapy with gonadotropins effectively induces spermatogenesis and increases the chances of successful reproduction. However, the optimal treatment modality and schedule, and required duration of treatment have not been determined. A 27-year-old man presented with erectile and ejaculatory disorder. Endocrinological examinations revealed isolated luteinizing hormone-releasing hormone (LHRH) deficiency of the hypothalamus, resulting in hypogonadotropic hypogonadism. No causative abnormality was detected in imaging studies. Having a diagnosis of adult-onset hypogonadotropic hypogonadism, the patient received pulsatile subcutaneous human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG). Hypogonadism did not improve with hCG/hMG combination therapy. He was successfully treated with the replacement therapy from hMG into recombinant human follicular-stimulating hormone (rhFSH) for induction of spermatogenesis, along with pregnancy in the female partner.

A 59-year-old man visited another hospital with a chief complaint of malaise. Radiological examinations revealed a renal cell carcinoma associated with horseshoe kidney. He was referred to our hospital. The patient was successfully treated with open partial nephrectomy following isthmus division. Histological findings exhibited grade 2, pT1a, clear cell type, renal cell carcinoma. He is free of disease at twelve months after the operation.

Androgen-independent prostate cancer eventually develops metastasis, and radical treatment may not be possible for patients at this stage. In this study, we examined the gene-expression profiles of two prostate cancer cell lines, LNCaP (androgen-dependent) and C4-2 (androgen-independent), using cDNA-microarray hybridization. We focused on the expression of alpha-methylacyl-CoA racemase (AMACR), whose expression is much higher in C4-2 than in LNCaP, and investigated its biological role in acquisition of androgen-independent cancer growth. Immunohistochemistry and Western blot analysis of subcellular fractions revealed that AMACR expression was much stronger in C4-2 than in LNCaP. Inhibition of AMACR expression using AMACR-siRNA induced an increase in the expression of androgen receptor (AR) and B-cell translocation gene 1, along with a decrease in the expression of genes associated with cancer progression, including insulin-like growth factor I and platelet-derived growth factor alpha, in C4-2 with compared to non-treated C4-2. BrdU analysis and MTT assay demonstrated that AMACR inhibition induced a significant decrease of cell viability in C4-2 when cultured in androgen-depleted serum, becoming consistent with that of LNCaP, suggesting that AMACR inhibition may induce an increase in the expression of AR and characteristic conversion of prostate cancer cells from hormone independency to hormone dependency. We suggest that AMACR inhibition may be a new strategy for treatment of patients with hormone-refractory prostate cancer.

Between January 1997 and February 2005, a total of 106 patients with superficial bladder cancer were treated with transurethral resection of bladder tumor followed by intravesical instillation of Tokyo 172 strain bacillus Calmette-Guerin (BCG) once a week for six weeks. The endpoints were tumor recurrence, tumor progression, and disease-specific survival. At a median follow-up of 27 months (range 2 to 105 months), 67 patients (63.2%) were recurrence-free and superficial recurrence including disease progressed with local invasion was noted in 39 patients (36.8%). The non-recurrence rate at one and three years were 75.9 and 54.6%. Twenty-four patients received an additional course of BCG instillation, and 14 (58.3%) showed no further recurrence. Thus, the overall success rate of 2 courses of BCG instillation was 76.4% (81 of 106 patients). Nine patients (8.5%) had progression and died of cancer. There was no significant differernce in recurrence rate among tumor characteristics. However, there was a significant differernce in survival rate between non-invasive and invasive tumor shape (p = 0.0189). Univariate analysis (Cox's proportional hazard model) demonstrated that tumor shape was associated with survival (p = 0.0486). Multivariate analysis demonstrated that gender and tumor shape were associated with survival (p = 0.0183, 0.025). Adverse effects included bladder irritability in 16 patients (15.1%), gross hematuria in 15 (14.2%), fever in 24 (22.6%), contracted bladder in 1 (0.9%) and interstitial pneumonitis in 1 (0.9%). Interstitial pneumonitis improved after pulse steroid therapy. BCG was found to be very useful for the treatment of superficial bladder cancer. Intravesical BCG instillation was effective for first recurrent superficial bladder cancer because of the low recurrence rate after a second instillation of BCG.

Intravesical chemotherapy is performed after transurethral resection of bladder tumor (TURBT) for superficial bladder cancer. We conducted a prospective randomized controlled study on the prophylactic effects of intravesical instillation of epirubicin (EPI) against recurrence to determine the effective administration schedule. Between April 1999 and March 2003, 54 patients with superficial bladder tumor (pTa or pT1, and G1 or G2 cancer) were assigned to two groups (25 in Group A, 29 in Group B) after TURBT. The schedule of instillation (intravesically 40 mg of EPI dissolved in 40 ml saline) was subsequently once every two weeks for 3 months (7 times) starting one week after TURBT (Group A, short period), and subsequently added every two weeks for 3 months starting 6 months after TURBT (Group B, long period). The patients were followed up by cystoscopy and urinary cytology. There was no significant difference in non-recurrence rates after either one year (A; 62.5%, B; 82.8%) or three years (A; 53.6%, B; 67.3%). A univariate analysis demonstrated that tumor grade and staging were significant predictors of high risk for recurrence. A multivariate analysis performed by using the Cox's proportional hazard model showed that the schedule of instillation was an independent prognostic factor for reccurence. In the present study, only 2 patients showed progression and one patient died of UC. There was no adverse event that forced discontinuation of the therapy. In conclusion, epirubicin instillation influenced the prevention of recurrence, but the benefit of long-term period was not confirmed.

Prostatic basal cell carcinoma (BCC), a distinctive variant of adenocarcinoma, is rare. We report a patient with pure basaloid BCC showing an extraprostatic extension and lymph node metastases. A 67-year-old man with urinary outlet obstruction was referred to our hospital. Digital rectal examination disclosed a stony hard prostate. Serum prostate-specific antigen and prostatic acid phosphatase were within the normal range. Transrectal needle biopsy of the prostate was followed by transurethral resection as symptomatic treatment. The lesion was diagnosed histopathologically as BCC. Despite antiandrogen therapy distant metastases developed, and the patient died 5 months postoperatively. We discuss the histological and immunohistochemical findings in this case.

Nuclear factor-kappaB (NF kappaB) plays a pivotal role in cancer progression. In this study, we developed a decoy cis-element oligo-deoxyribonucleic acid against NF kappaB-binding site (NF kappaB-decoy), which effectively inhibits NF kappaB activity, and tested the effect of combined therapy comprising local transfection of NF kappaB-decoy into the liver and transportal injection of paclitaxel on cancer growth and metastasis using an orthotopic murine model of colon cancer liver metastasis. For NF kappaB-decoy transfection, we employed a novel approach using ultrasound exposure with an echocardiographic contrast agent, Optison. We examined the influence of NF kappaB-decoy transfer on susceptibility to paclitaxel in cancer cells and the mechanism involved using several in vitro analysis systems. We then studied the in vivo effect of combined NF kappaB-decoy transfer and paclitaxel in preventing cancer progression using a murine model of liver metastasis created by splenic injection of a human colon cancer cell line, HT29. In vitro experiments, including MTT-assay, fluorescence-activated cell sorter and cDNA array analysis, revealed that NF kappaB-decoy transfer significantly increased the susceptibility of cancer cells to paclitaxel, and that decreased expression of anti-apoptotic genes along with increased expression of genes relevant to the apoptosis-promotor may be involved. In vivo experiments showed that local transfection of NF kappaB-decoy into the liver followed by portal injection of paclitaxel effectively induced cancer cell apoptosis in the liver metastasis, and significantly prolonged animal survival compared to controls, without notable side effects. In conclusion, a combination of local NF kappaB-decoy transfer into the liver and transportal injection of paclitaxel may be a safe and effective new therapy for liver metastasis., ((c) 2007 Wiley-Liss, Inc.)

Objectives: We conducted the present study to evaluate the safety profile and therapeutic value of a combination of etoposide and fosfestrol for treatment of hormone-refractory prostate cancer (HRPC)., Methods: Forty patients with HRPC were included in the study. The median age was 71 years (range, 50-86 years), the Gleason's score ranged from 5 to 10, and the median prostate-specific antigen level was 62.6 ng/mL (range, 4.738-30789 ng/mL). The patients received oral etoposide 25 mg/d and fosfestrol 300 mg/d., Results: The response rate in terms of measurable disease, serum prostate-specific antigen level, and overall evaluation was 36.8% (CR: 18.4%; PR: 18.4%), 80% (CR: 55%; PR: 25%), and 40% (CR: 20%; PR: 20%) with a median duration of response of 13.6, 13.5, and 13.5 months, respectively. An objective clinical response for overall evaluation was shown by 90% (CR: 20%; PR: 20%; SD: 50%) of the patients, with a median response duration of 15.7 months; 16 patients (40%) are currently alive without recurrence after a median follow-up period of 21.2 months. The overall survival and progression-free survival was 30.5% and 28.8% at 40 months, respectively. No grade III toxicities occurred in any of the patients. Serial measurements in 34 patients using the Functional Assessment of Cancer Therapy-Prostate showed a significant improvement in quality of life as a result of the therapy., Conclusions: The combination of oral etoposide and fosfestrol is active in patients with HRPC. The regimen is tolerable and has a significant impact on quality of life as measured by the Functional Assessment of Cancer Therapy-Prostate in a limited sample of patients.

Objective: We tested the usefulness of combined therapy using balloon-occluded arterial infusion (BOAI) of cisplatin and hemodialysis, which delivers an extremely high concentration of cisplatin to the site of a tumor without systemic adverse effects, with concurrent radiation in patients with locally advanced bladder cancer., Methods: Patients underwent transurethral resection of the bladder tumor followed by BOAI of cisplatin (100, 200, or 300 mg) concurrent with hemodialysis, via both common iliac veins, for 2 hours after initiation of BOAI. A total of 60.4 Gy of radiation was delivered, starting from the day of BOAI., Results: Forty-one patients (30 males and 11 females, aged 55-98 years) were enrolled and assessable for toxicity and response. None of the patients suffered grade II or more severe toxicities; some experienced grade I blood/bone marrow toxicity, gastrointestinal toxicity, or neuropathy. All patients with histologically confirmed transitional cell carcinoma stage T2 or T3 (29 patients) achieved a complete response and were able to retain their bladder with no evidence of recurrent disease or distant metastasis at a mean follow-up of 132 weeks (range 8-648 weeks) after therapy. Patients with stage T4 tumors, besides transitional cell carcinoma, or lymph node involvement had stable or progressive disease., Conclusion: This therapy is a new strategy for patients with locally advanced bladder cancer. It can be a curative treatment not only in patients for whom total cystectomy is indicated, but also in patients whose condition is not amenable to curative treatment and for whom merely palliative treatment would otherwise seem the only option.

Prostatic stromal sarcoma (PSS) is an unusual lesion that is reported only occasionally. Here we describe a case of prostatic stromal sarcoma in a 33-year-old man who had complained of perineal pain. The serum prostate-specific antigen (PSA) level was above the normal limit at 5.8 ng/ml, and abdominal computed tomography (CT) revealed a giant mass in the retrovesical region. Chest CT demonstrated lung metastases. Specimens obtained by transrectal needle biopsy of the prostate suggested a mesenchymal tumor, but a precise diagnosis required a larger specimen. Palliative transurethral resection (TUR-P) was performed because of obstruction of the urogenital tract, and the final diagnosis was made from this specimen. The tumor contained yellowish gelatinous materials, and the stromal element appeared histologically malignant, with increased cellularity, mitotic figures and pleomorphism. The histological diagnosis was PSS, and the patient received VIP (etoposide, ifosfamide, cisplatin) chemotherapy regimen. However, the pelvic mass continued to increase in size, and the patient's condition rapidly deteriorated and he died. Sarcoma of the prostate gland showing aggressive behavior is quite rare. The detailed histological and immunohistochemical findings in this case are reported, together with a review of the literature.