Androgen deprivation therapy for prostate cancer and the risk of hematologic disorders.

PURPOSE: This study aimed to investigate the association between androgen deprivation therapy (ADT) and the risk of subsequently developing hematologic disorders in patients with prostate cancer. MATERIALS AND METHODS: This population-based nationwide cohort study utilized data from the Taiwan National Health Insurance Research Database between 1997 and 2013. The patients were divided into three groups-those who received ADT only (ADT-only group), those who had radiotherapy (RT) only (RT-only group), and those treated with radical prostatectomy (RP) only (RP-only group). The study outcome was newly diagnosed hematologic disorder, including anemia and hematologic malignancy. Propensity score-matched, Cox regression, and Kaplan-Meier curve analyses were performed to investigate the risk of subsequently developing hematologic disorders after ADT. RESULTS: Of the 17,168 patients with prostate cancer who were included in the study, 13,318 met the inclusion and exclusion criteria. After propensity score matching, 1,797, 1,797, and 1,797 patients treated with ADT only, RT only, and RP only, respectively, who had a median follow-up period of 4.32 years were included in the study cohort. Compared with the patients treated with RP only, those who received ADT and RT were significantly at increased risk of subsequently developing hematologic disorders (ADT: adjusted hazard ratio [aHR]: 1.60, 95% confidence interval [CI]: 1.29-1.97; RT: aHR, 1.98, 95% CI: 1.62-2.42) according to the Cox regression analysis. Based on the Kaplan-Meier curve analysis, patients with bone metastasis who received ADT only had the lowest cumulative probabilities of not developing hematologic disorders. Moreover, a significantly increased risk of hematologic disorders was observed with the increasing duration of ADT (P for trend < .001). CONCLUSIONS: The use of ADT in patients with prostate cancer may increase the risk of subsequently developing hematologic disorders.

Incidence of Cellulitis Following Acupuncture Treatments in Taiwan.

Background: Cellulitis is a complication of acupuncture, but the risk factors and annualized incidence remain unclear. Objective: This study analyzed the incidence and risk factors of cellulitis related to acupuncture in a cohort of one million participants derived from Taiwan's Longitudinal Health Insurance Database. Methods: We tracked this cohort between 1997 and 2012 and recorded all outpatient medical information including diagnosis and treatment. Patients were categorized according to age, gender, comorbidities, residential area, and number of acupuncture treatments. We compared the incidence and risk of cellulitis between different demographics and comorbidities by logistic regression analysis and adjusted odds ratio (aOR) with a 95% confidence interval (95% CI). Results: We included 407,802 patients and 6,207,378 acupuncture treatments. The incidence of cellulitis after acupuncture was 64.4 per 100,000 courses of acupuncture treatment. The most common sites of cellulitis after acupuncture were the legs, feet, and face. Comorbidity was associated with post-acupuncture cellulitis; a multivariate logistic regression analysis showed that chronic kidney disease (aOR, 1.71; 95% CI, 1.55-1.88), rheumatoid arthritis (aOR, 1.86; 95% CI, 1.21-3.60), liver cirrhosis (aOR, 1.23; 95% CI, 1.15-1.32), diabetes mellitus (aOR, 1.69; 95% CI, 1.57-1.82), stroke (aOR, 1.44; 95% CI, 1.31-1.58), varicose veins (aOR, 2.38; 95% CI, 2.17-2.84), or heart failure (aOR, 1.81; 95% CI, 1.65-1.98) significantly increased cellulitis. Repeated exposure to acupuncture treatment was associated with an increased risk of cellulitis. Conclusions: A variety of chronic diseases may increase the risk of cellulitis after acupuncture. Physicians asked about past medical history before acupuncture might help to reduce cellulitis.

Incidence of iatrogenic pneumothorax following acupuncture treatments in Taiwan.

BACKGROUND: Pneumothorax is a rare complication of acupuncture and the risk factors are unclear. OBJECTIVE: This study analysed the incidence of post-acupuncture pneumothorax requiring hospitalisation in a one-million-sample cohort derived from Taiwan's National Health Insurance Research Database. METHODS: We tracked this cohort between 1997 and 2012 and recorded all medical insurance information. Subjects were categorised according to gender, insurance amount, comorbidities, residential area, and number of acupuncture treatments. Pneumothorax risk was evaluated according to different demographic and medical variables by logistic regression analysis using an adjusted odds ratio (aOR) with a 95% confidence interval (95% CI). RESULTS: Overall, 411 734 patients undergoing 5 407 378 acupuncture treatments were identified with data collected over the first 7 days after acupuncture. The incidence rates of iatrogenic pneumothorax were 0.87 per 1 000 000 acupuncture treatments overall and 1.75 per 1 000 000 acupuncture treatments in "at-risk" anatomical areas. Multivariate logistic regression demonstrated that a history of thoracic surgery (aOR 7.85, 95% CI 3.49 to 9.25), chronic bronchitis (aOR 2.61, 95% CI 1.03 to 6.87), emphysema (aOR 4.87, 95% CI 1.03 to 7.96), pneumonia (aOR 2.09, 95% CI 1.44 to 2.72), tuberculosis (aOR 3.65, 95% CI 1.39 to 9.56), and lung cancer (aOR 3.85, 95% CI 1.53 to 9.73) may increase the post-acupuncture risk of iatrogenic pneumothorax. Men had a higher risk of pneumothorax than women (aOR 3.41, 95% CI 1.36 to 8.57). The number of treatments was not associated with risk of pneumothorax. CONCLUSIONS: Patients with a history of lung disease including chronic bronchitis, emphysema, tuberculosis, lung cancer and pneumonia, and a history of thoracic surgery, might have an increased post-acupuncture risk of pneumothorax. This information may possibly help physicians avoid post-acupuncture pneumothorax.

The association between epididymo-orchitis and prostate cancer: A nationwide population-based cohort study.

To determine whether epididymo-orchitis, a common infectious disease among men, is associated with subsequent prostate cancer (PCa) via a nationwide cohort study.This nationwide population-based study of patients treated from 2001 to 2013 included a total of 4991 patients with epididymo-orchitis as the study group and 19,922 matched patients without epididymo-orchitis as a control group. We tracked the patients in both groups for a 5-year period to identify any new cases of PCa. Cox proportional hazards regressions were performed to calculate the hazard ratio (HR) of PCa during this 5-year follow-up period.Of the 24,913 patients in the study, 235 (0.9%) were newly diagnosed with PCa during the 5-year follow-up period; 77 (1.5%) of those were from the epididymo-orchitis group and 158 (0.8%) were from the control group. Compared to the patients without epididymo-orchitis, the adjusted HR for PCa for the patients with epididymo-orchitis was 1.56 (95% confidence interval [CI]: 1.18-2.06) during the 5-year follow-up period. Ages of more than 70 years, higher incomes, hypertension, and hyperlipidemia were more strongly associated withPCa in the study group than in the control group.The results were associated with a 56% increased risk for PCa among patients with epididymo-orchitis. Epididymo-orchitis may play an etiological role in the development of PCa in Asian populations. Further studies are warranted, however, to investigate the relationship between epididymo-orchitis and PCa.

Androgen deprivation therapy and the risk of tenosynovitis in prostate cancer patients.

OBJECTIVES: Androgen deprivation therapy (ADT) use in prostate cancer (PCa) patients has been reported to have an association with rheumatoid arthritis. We aimed to assess the impact of ADT on the subsequent risk of tenosynovitis. METHODS: Using data from the National Health Insurance Research Database of Taiwan between 2001 and 2013, 3309 patients with PCa were identified. Among them, 729 ADT patients comprised the study group with 729 matched non-ADT controls. We used a 1:1 propensity score matched analysis. The demographic characteristics and comorbidities of the patients were analyzed; Cox proportional hazards regression was used to calculate the hazard ratios (HR) for the risk of tenosynovitis. RESULTS: There were 224 (15.3%) patients with newly diagnosed tenosynovitis. Compared with non-ADT patients, ADT patients had a lower risk of subsequent tenosynovitis with an adjusted HR of 0.38 [95% confidence interval (CI) 0.28-0.51; P < 0.001]. CONCLUSIONS: ADT use apparently did not increase the risk of tenosynovitis in patients with PCa. Further studies are warranted to assess the clinical significance.

The association of cellulitis incidence and meteorological factors in Taiwan.

Cellulitis is a common infection of the skin and soft tissue. Susceptibility to cellulitis is related to microorganism virulence, the host immunity status and environmental factors. This retrospective study from 2001 to 2013 investigated relationships between the monthly incidence rate of cellulitis and meteorological factors using data from the Taiwanese Health Insurance Dataset and the Taiwanese Central Weather Bureau. Meteorological data included temperature, hours of sunshine, relative humidity, total rainfall and total number of rainy days. In otal, 195 841 patients were diagnosed with cellulitis and the incidence rate was strongly correlated with temperature (γS = 0.84, P < 0.001), total sunshine hours (γS = 0.65, P < 0.001) and total rainfall (γS = 0.53, P < 0.001). The incidence rate of cellulitis increased by 3.47/100 000 cases for every 1° elevation in environmental temperature. Our results may assist clinicians in educating the public of the increased risk of cellulitis during warm seasons and possible predisposing environmental factors for infection.

Association between Periodontal Disease and Subsequent Sjögren's Syndrome: A Nationwide Population-Based Cohort Study.

Xerostomia (dry mouth) is the cardinal symptom of Sjögren's syndrome (SS), which is an autoimmune disease involving the exocrine glands and other organs. Xerostomia may predispose patients to periodontal disease (PD) and an association between SS and PD has been reported. This association may be bidirectional; therefore, we conducted this study to investigate the risk of SS in patients with PD using data from the National Health Insurance Research Database of Taiwan. A total of 135,190 patients were enrolled in our analysis. In all, 27,041 patients with PD were matched by gender, age, insured region, urbanization and income, with cases and controls in a 1:4 ratio. Both groups were followed and the risks of SS were calculated by Cox proportional hazards regression. Finally, 3292 (2.4%) patients had newly diagnosed SS. Patients with PD had a significantly higher risk of subsequent SS (903 (3.3%) vs. 2389 (2.2%), adjusted hazard 1.47, 95% confidence interval: 1.36⁻1.59). In conclusion, patients with PD had an approximately 50% increased risk of subsequent SS. Physicians should be aware of the symptoms and signs of SS in patients with PD.

Androgen deprivation therapy for prostate cancer and the risk of autoimmune diseases.

BACKGROUND: Androgen deprivation therapy (ADT) has been a mainstay of treatment for advanced prostate cancer (PCa), but limited studies have been performed to investigate the association between ADT and autoimmune diseases. METHODS: We conducted a population-based nationwide cohort study of 17,168 patients newly diagnosed with PCa between 1996 and 2013 using the National Health Insurance Research Database (NHIRD) of Taiwan. Cox proportional hazards models with 1:1 propensity score-matched analysis were used to investigate the association between ADT use and the risk of autoimmune diseases. The autoimmune diseases included Graves' disease, Crohn's disease, psoriasis, systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis, Guillain-Barre syndrome, Sjogren's syndrome, myasthenia gravis, pernicious anemia, hereditary hemolytic anemia, polyarteritis nodosa, Celiac disease, uveitis, polymyalgia rheumatica, dermatomyositis, Hashimoto's thyroiditis, hypersensitivity vasculitis, Behcet's disease, polymyositis, alopecia areata, Wegener's granulomatosis, ulcerative colitis, autoimmune hemolytic anemia, pemphigus, multiple sclerosis, systemic sclerosis, Goodpasture syndrome, giant cell arteritis, thromboangitis obliterans, arteritis obliterans, and Kawasaki disease. The duration of ADT use as a time-dependent variable was also examined for its association with autoimmune diseases. We also performed six secondary analyses. RESULTS: Of the 17,168 selected PCa patients, 14,444 patients met all the inclusion and exclusion criteria. After propensity score matching, 5590 ADT users and 5590 non-ADT users were included in the study cohort. A propensity score-matched analysis (adjusted hazard ratio (aHR), 0.619, 95% confidence interval (CI), 0.51-0.75, P < 0.001) demonstrated a significantly decreased risk of autoimmune diseases in ADT users. A significant decrease in the risk of autoimmune diseases with increasing ADT duration was also demonstrated (P < 0.001). CONCLUSIONS: We observed that ADT use in patients with PCa was associated with a decreased risk of autoimmune diseases. These novel findings provide a potential role for androgen deprivation therapy in the modification of inflammation and autoimmunity in Asian patients with prostate cancer.

Statin reduces the risk of dementia in diabetic patients receiving androgen deprivation therapy for prostate cancer.

BACKGROUND: Androgen deprivation therapy (ADT) has been reported to increase the risk of dementia. Statin use decreases the risk of dementia. This study is aimed to investigate the association of statin use and dementia in type 2 diabetic (T2DM) patients receiving ADT. METHODS: Using the National Health Insurance Research Database of Taiwan, we conducted a population-based nationwide cohort study of T2DM patients newly diagnosed with prostate cancer (PCa) between 1998 and 2013. To test statin effects on dementia in T2DM patients receiving ADT, cox proportional hazards models with 1:1 propensity score-matched analysis were used. We divided the study subjects into a statin group and a statin-naive group. The primary outcome was dementia. RESULTS: Of the 9855 selected T2DM patients newly diagnosed with PCa between 1998 and 2013, 5427 patients received ADT for their PCa. After propensity score matching, 1006 statin users and 1006 non-statin users were included in the study cohort, with a mean follow-up period of 3.5 years for the statin group. Among those patients, 179 (8.7%) were newly diagnosed with dementia. A propensity score-matched analysis (hazard ratio = 0.70, 95% confidence interval = 0.52-0.94) demonstrated a significantly decreased risk of subsequent dementia in the statin users with an absolute risk reduction by 1%. A significant decrease in the risk of dementia with increasing statin duration was also demonstrated (P for trend = 0.002). CONCLUSIONS: Statin use in T2DM patients receiving ADT for PCa had decreased risk of dementia, with statin adherence and intensity augmenting this benefit.

Increased Risk of Ulcerative Colitis in Patients with Periodontal Disease: A Nationwide Population-Based Cohort Study.

Both periodontal disease (PD) and inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are important diseases of the alimentary tract. Microbiome and immune-mediated inflammatory processes play important roles in these diseases. An association between PD and IBD may exist. This study investigated the risk of IBD in patients with PD. This study used data from the National Health Insurance Research Database of Taiwan from 1996 to 2013. A total of 27,041 patients with PD were enrolled as a study group, and 108,149 patients without PD were selected as the control group after matching by gender, age, insured region, urbanization, and income with a 1:4 ratio. Cox proportional hazards regression was used to calculate the risk of IBD. Of the 135,190 participants enrolled in this study, 5392 (4%) with newly diagnosed IBD were identified. The overall incidence of subsequent IBD was similar in both groups (3.8% vs. 4%, adjusted hazard ratio (aHR) = 1.01, 95% confidence interval (CI): 0.94⁻1.08). However, an increased risk of UC in the PD group was found after adjusting confounding factors (aHR: 1.56, 95% CI: 1.13⁻2.15; p < 0.05). This study demonstrated that patients with PD had approximately one-half higher risk of subsequent UC. Further studies are warranted to elucidate the relationship between PD and UC.

Depression Negatively Impacts Survival of Patients with Metastatic Prostate Cancer.

The prevalence of depression in patients with cancer is high, especially for patients with advanced cancer. In this study, we evaluated the prevalence of depression in prostate cancer patients in Taiwan and the association between depression and mortality in prostate cancer. This study included 1101 newly diagnosed patients with prostate cancer. We tracked the medical information of these patients from diagnosis until the end of 2012. Patients were divided into two groups according to presence or absence of depression diagnosis, and were further divided into three stages by initial treatments: localized or locally advanced, metastatic, and castration-resistant prostate cancer. Of 1101 participants, 267 (24.3%) had depression. By the end of the follow-up period (M = 8.30 ± 3.12 years), 77 (28.8%) patients in the depression group and 194 (23.3%) in the non-depressed group died. Depression was associated with higher mortality risk, (aHR 1.37; 95% CI [ 1.04⁻1.80]; p value 0.01). Patients in the metastatic prostate cancer group with depression had a significantly higher mortality risk compared to the non-depressed group, (aHR, 1.49; 95% CI [1.05⁻2.11]; p value 0.02). The impact of depression on mortality risk was not significant in either the localized or locally advanced or the castration-resistant prostate cancer groups. Our study showed that depression is related to an increased mortality risk for patients with prostate cancer, especially for metastatic prostate cancer. These results indicate that urologists should pay attention to the mood and psychiatric disorders of patients with prostate cancer.

No increased risk of psoriasis in patients receiving androgen deprivation therapy for prostate cancer: a 17-year population-based study.

OBJECTIVE: Androgen deprivation therapy (ADT) use in prostate cancer (PCa) patients has been reported to exacerbate the course of psoriasis. We aimed to assess the impact of ADT on the subsequent risk of psoriasis. METHODS: We utilized data from the National Health Insurance Research Database of Taiwan between 1996 and 2013. In total, 17,168 patients with PCa were identified; 5,141 ADT patients comprised the study group with 5,141 matched non-ADT controls. We used 1:1 propensity score-matched analysis. The demographic characteristics and comorbidities of the patients were analyzed; Cox proportional hazards regression was used to calculate the HRs for the risk of psoriasis. RESULTS: Eighty-nine (0.87%) patients with newly diagnosed psoriasis were identified. Compared with non-ADT patients, ADT patients had similar risk of subsequent psoriasis with an HR of 0.95 (95% CI 0.63-1.45; P=0.816). However, a higher risk of psoriasis was observed in angiotensin-converting enzyme inhibitors patients (adjusted HR 2.14, 95% CI 1.09-4.20; P<0.05). CONCLUSION: ADT use did not increase risk of psoriasis in patients with PCa. Further studies are warranted to assess the clinical significance.

Postpartum Depression and Subsequent Autoimmune Diseases in Taiwan.

Postpartum depression (PPD) is one of the most common examples of postnatal morbidity, but the subsequent risks of autoimmune diseases in patients with PPD have yet to be fully investigated. This nationwide population-based study utilized data of the National Health Insurance Research Database of Taiwan for the period from 1996 to 2013. In total, 45,451 women with primiparity were identified. Among them, 542 patients with PPD were enrolled as a study group while 2165 matched patients without PPD were enrolled as a control group. The demographic characteristics and comorbidities of the patients were analyzed, and Cox regression analysis was applied to calculate the hazard ratios for the risk of autoimmune diseases. Of the 2707 women enrolled in this study, 469 (17.3%) patients with newly diagnosed autoimmune diseases were identified, including 123 (22.7%) in the PPD group and 346 (16%) in the non-PPD group. After adjusting for confounding factors, it was determined that the patients with PPD had a significantly higher risk of subsequent autoimmune diseases (adjusted hazard ratio (aHR): 1.61, 95% confidence interval (CI): 1.30⁻1.99; p < 0.001). Specifically, increased risks of pernicious anemia (aHR: 3.85, 95% CI: 2.06⁻7.22), rheumatoid arthritis (aHR: 2.62, 95% CI: 1.28⁻5.39), and Graves' disease (aHR: 1.57, 95% CI: 1.05⁻2.33) were observed in the PPD group. This study demonstrated that patients with PPD have higher risks of subsequent autoimmune diseases, especially pernicious anemia, rheumatoid arthritis, and Graves' disease. This useful information provides physicians with clues regarding the associations between autoimmune diseases and PPD.

The association between scabies and myasthenia gravis: A nationwide population-based cohort study.

Scabies is an infectious inflammatory pruritic skin disease. Cytokine-mediated inflammatory processes contribute to the pathologic mechanism in scabies. Myasthenia gravis (MG) is also an autoimmune disease that is mediated by cytokines. The study aimed to investigate the association between scabies and myasthenia gravis. We conducted a nationwide population-based cohort study utilized data from the National Health Insurance Research Database (NHIRD) of Taiwan. Patients with scabies (n=5429) and control subjects without scabies (n=20,176) were enrolled. We tracked the subjects in both groups for a 7-year period to identify new onset MG. Cox regression analysis was performed to calculate the hazard ratio (HR) for MG. A total of 25,605 patients were enrolled in the study, including 5429 patients in the scabies group and 20,176 in the control group. There were 40 (0.7%) patients from the scabies group and 84 (0.4%) subjects from the control group who were newly diagnosed with MG during the 7-year follow-up period. The scabies patients had a significantly increased risk of MG, with an adjusted HR of 1.27 (95% confidence interval [CI] 1.01-1.89). As such, prompt diagnosis and treatment of scabies may decrease the risk of subsequent MG.

Traditional Chinese medicine therapy reduces the catheter indwelling risk in dementia patients with difficult voiding symptoms.

ETHNOPHARMACOLOGICAL RELEVANCE: Dementia is an international health issue in elder people. Indwelling catheters to address voiding problems in patients with dementia introduce risks of urinary tract infection or urethral trauma. Traditional Chinese medicine (TCM) is widely used to treat difficult voiding symptoms in Taiwan. We investigated the long-term clinical effects of TCM for reducing the risk of indwelling catheterization in dementia patients with difficult voiding symptoms. MATERIALS AND METHODS: We used National Health Insurance Research Database to conduct a retrospective study of dementia patients with difficult voiding symptoms between 1997 and 2012 in Taiwan. We collected medical data from the onset of dementia to post-catheter insertion. Cox regression proportional hazards model and cumulative incidence of the urinal catheterization curve were used to determine the association between catheter indwelling risk and TCM use. RESULTS: Data from 11069 patients with dementia was assessed, and 3982 participants who received medication for relief voiding symptoms were categorized into 2 groups: 2121 (53.3%) were TCM users and 1861 (46.7%) were TCM non-users with a mean follow-up period of 7.25 years. Cox regression demonstrated that using TCM may decrease the need for indwelling catheterization in patients with dementia (adjusted hazards ratio (aHR) =0.58, 95% confidence interval (95% CI): 0.52-0.66) compared to TCM non-users. A relationship between longer TCM use and reduced urinary retention with indwelling catheter use was observed, especially in patients who used TCM for ≥200 days (aHR =0.46, 95% CI: 0.39-0.55). Ji-Sheng-Shen-Qi-Wan (aHR =0.44, 95% CI: 0.21-0.88), Wu-Ling-San (aHR =0.47, 95% CI: 0.16-0.92), Zhi-Bai-Di-Huang-Wan (aHR =0.50, 95% CI: 0.26-0.94), were the most 3 beneficial TCM formulae. CONCLUSIONS: The results of this study suggest that TCM is associated with a reduced risk of indwelling catheterization in patients with dementia, with enhanced benefits from longer durations of TCM use.

The effect of nocturia on sleep quality and daytime function in patients with lower urinary tract symptoms: a cross-sectional study.

BACKGROUND: Nocturia has been proven to have a negative impact on the quality of life and sleep quality in general elderly population. However, there are limited studies on the quantitative effect of nocturia on sleep quality and daytime dysfunction, specifically in patients with lower urinary tract symptoms. PATIENTS AND METHODS: During March 1, 2015 to December 31, 2015, a total of 728 patients who visited our urology department due to voiding dysfunction and experienced nocturia at least once per night were enrolled. Three questionnaires were administered to them after obtaining their written consents. Pittsburgh Sleep Quality Index (PSQI) questionnaire, Epworth Sleepiness Scale (ESS) questionnaire, and International Prostate Symptom Score (IPSS) questionnaire were applied to evaluate their sleep quality, daytime dysfunction, and voiding problems, respectively. Statistical analysis of the impact of nocturia on sleep quality and daytime dysfunction was performed. RESULTS: The mean age of patients was 61 years, with a male-to-female ratio of 2.7. The mean nocturia number was 3.03. The IPSS, PSQI, and ESS scores were 17.56, 8.35, and 8.22, respectively. The nocturia number increased with age and was significantly correlated to ESS score (daytime dysfunction) and PSQI total score (sleep quality) in overall group. Among subgroups divided by age and sex, there was a significant correlation between nocturia number and daytime dysfunction in male patients or patients younger than 65 years. CONCLUSION: In patients with lower urinary tract symptoms, nocturia number increased with age and was significantly correlated with poor sleep quality. Nocturia plays an important role in patients younger than 65 years in daytime dysfunction.

Cooperative dual-activity targeted nanomedicine for specific and effective prostate cancer therapy.

A key issue in cancer therapy is how to enhance the tumor-targeting efficacy of chemotherapeutic agents. In this study, we developed a cooperative dual-targeted delivery platform for paclitaxel (PTX) that has potential application as a powerful prostate cancer treatment. The nanomedicine was prepared by first conjugating PTX to nontoxic high-magnetization nanocarriers which can be actively guided and targeted by an external magnet. Next, the surface was functionalized with carboxylated o-(2-aminoethyl)polyethyleneglycol (NH(2)-EPEG-COOH) to enable uptake by the reticuloendothelial system. Antiprostate-specific membrane antigen antibodies (APSMAs) were then conjugated onto the carrier to recognize the extracellular domain of the prostate-cancer specific membrane antigen (PSMA), thus binding to cancer cells as a secondary active targeting mechanism. We found a significant enhancement of PTX concentration at the tumor site by nearly 20-fold. In addition, the drug half-life was prolonged more than 4.1-fold (from 24 to 99 h) at 37 °C. Low-dose (4.5 mg/kg) injection of the dual-targeted therapeutic nanomedicine in the presence of magnetic targeting significantly prolonged the median survival of nude mice from 35 to 58 days compared to mice that received a high dose (6 mg/kg) of free PTX. This report demonstrates the potential utility of targeted nanomedicine in the clinical treatment of cancer.

Superhigh-magnetization nanocarrier as a doxorubicin delivery platform for magnetic targeting therapy.

The aim of this study describes the creation of superhigh-magnetization nanocarriers (SHMNCs) comprised of a magnetic Fe(3)O(4) (SHMNPs) core and a shell of aqueous stable self-doped poly[N-(1-one-butyric acid)]aniline (SPAnH), which have a high drug loading capacity (∼27.1 wt%) of doxorubicin (DOX). The SHMNCs display superparamagnetic property with a magnetization of 89.7 emu/g greater than that of Resovist (a commercial contrast agent used for magnetic resonance imaging; 73.7 emu/g). Conjugating the anticancer drug DOX to these nanocarriers enhances the drug's thermal stability and maximizes the efficiency with which it is delivered by magnetic targeting (MT) therapy to MGH-U1 bladder cancer cells, in part by avoiding the effects of p-glycoprotein (P-gp) pumps to enhance the intracellular concentration of DOX. The high R2 relaxivity (434.7 mM(-1)s(-1)) of SHMNCs not only be a most effective MT carrier of chemotherapeutic agent but be an excellent contrast agent of MRI, allowing the assessment of the distribution and concentration of DOX in various tissues and organs. This advanced drug delivery system promises to provide more effective MT therapy and tumor treatment using lower therapeutic doses and potentially reducing the side effects of cardiotoxicity caused by DOX.

Prognostic value of TNM stage and tumor necrosis for renal cell carcinoma.

Our objective was to assess the value of tumor necrosis and other factors for predicting the outcome of renal cell carcinoma (RCC). Our study comprised 328 RCC patients who were surgically treated at this hospital between 2001 and 2006. The five-year survival data was analyzed using a Kaplan-Meier statistical analysis. The prognostic factors were evaluated with a univariate analysis using a log-rank test and multivariate analysis using the Cox proportional hazards regression method. The mean follow-up period for these patients was 46.5 months (median 45.2 months). The univariate analysis revealed that age, tumor stage, TNM stage, grade, tumor necrosis, and histological type were statistically significant prognostic factors. The multivariate analysis showed that the TNM stage and tumor necrosis were the most important predictive factors in the patients' overall survival. In the TNM stage with and without tumor necrosis, the five-year overall survival rates in stages I+II were 80.5% and 89.2%, respectively (p=0.115), where as the five-year survival rates in stages III+IV were 32.7% and 84.0%, respectively (p<0.001). Collectively, our present data revealed that tumor necrosis was an important predictive factor for survival in advanced stage RCC. In conclusion, both the TNM stage and tumor necrosis provided the most important prognostic factors of survival in RCC. Tumor necrosis proved to be a poor prognostic factor in advanced RCCs.

Epstein-Barr virus DNA load in tumour tissues correlates with poor differentiation status in non-muscle invasive urothelial carcinomas.

OBJECTIVE: To detect the correlation between the clinical staging, grading and genomic Epstein-Barr virus (EBV) viral numbers in tumour tissues of urothelial carcinoma patients. PATIENTS AND METHODS: From June 2004 to May 2008, 60 urothelial carcinoma patients (50 cases of bladder carcinoma and 10 of upper tract urothelial carcinoma (UTUC) were enrolled in the study. Eight patients who underwent transurethral resection of prostate for prostate hyperplasia and two patients receiving nephrectomy for non-function kidney were used as normal controls. The EBV viral copy numbers in genomic DNA were evaluated using a real-time PCR-based study. The BamHI W region of the Namalwa cell line was constructed to the plasmid clone and was used as standard curve for absolute quantitative PCR (Q-PCR). RESULTS: Epstein-Barr virus DNA was detected in 56% (28/50) and 60% (6/10) of the bladder and UTUC patients, respectively. The EBV DNA could not be detected in the normal control group. By pooling the UTUC and bladder patients in stage Ta,T1, the high copy number in fixed genomic DNA amount (100 ng/20 µL) was correlated with the high grading in stage Ta,T1 urothelial carcinoma (P = 0.014). The overall grading was not statistically associated with EBV copy number (P = 0.25). Although the copy numbers between paired tumour and normal tissues were not statistically different (P= 0.169), there were more copies of EBV in the normal tissues adjacent to the tumours than in those free from urothelial carcinoma. There was no significant difference between recurrence of non-muscle invasive bladder cancer and the presence of EBV (P > 0.05). CONCLUSIONS: Epstein-Barr virus DNA could be detected in the genome of the urothelial carcinoma specimens. The poor differentiation status was correlated with the high load of the EBV genome in non-muscle invasive urothelial carcinoma. However, recurrence-free survival was not greater in EBV-positive patients than in EBV-negative patients.