Clinical experiences with testosterone therapy: prostate safety

Due to a decrease in Leydig cell function, a considerable proportion of men over 50 years of age will develop hypogonadism. Consequently, loss of libido and several other testosterone-dependent symptoms may become evident. When decreased levels of biologically available testosterone are found, and corresponding symptoms are present, these men could be eligible for testosterone substitution therapy. Testosterone treatment in testosterone-deprived men has been shown to improve general well-being, osteoporosis, muscle atrophy, libido and - if present - anemia. Despite these positive effects, testosterone treatment has to be performed with caution. Although it has not been proven that elevation of the serum testosterone level to the normal range results in a greater risk of developing prostate cancer, the effects of testosterone on a prostate cancer already present are well established. Several studies have demonstrated that testosterone treatment does not result in a significant increase in serum levels of prostate-specific antigen (PSA) or prostate volume. The long-term effects, however, are currently unknown. For these reasons, testosterone treatment should be performed only when the presence of prostate cancer is unlikely; i.e. when PSA levels are within normal limits and digital rectal examination does not reveal any suspicious findings. These examinations may still miss some small prostate cancers that could be promoted by testosterone treatment. The determination of PSA levels under testosterone treatment is necessary every 3 months, at least for the first year. Steadily rising PSA levels require immediate cessation of testosterone administration and the initiation of further diagnostic procedures (prostate biopsy), to rule out prostate cancer.     

Male breast cancer

Male breast cancer (MBC) is a rare disease. However, as global populace ages, there is a trend to MBC increasing. Although aetiology is still unclear, constitutional, environmental, hormonal (abnormalities in estrogen/androgen balance) and genetic (positive family history, Klinefelter syndrome, mutations in BRCA1 and specially BRCA2) risk factors are already known. Clinic manifestation is painless hard and fixed nodule in the subareolar region in 75% of cases, with nipple commitment earlier than in women. Breast cancer has similar prognostic factors in males and females, among which axillary adenopathy (present in 40–55% cases) is the most important one. Although mammography, ultrasonography and scintigraphy can be useful tools in diagnosis; clinical assessment, along with a confirmatory biopsy, remains the main step in the evaluation of men with breast lesions. Infiltrating ductal carcinoma is the most frequent histological type. The established standard of care is modified radical mastectomy followed by tamoxifen for endocrine-responsive positive disease, although other options are being explored. While similarities between breast cancer in males and females exist, it is not appropriate to extrapolate data from female disease to the treatment of male. There is a need for specific multi-institutional trials to better understanding of clinicopathologic features and establishment of optimal therapy for this disease.     

The aging male in the 21st century

Background.?Prostate cancer incidence varies significantly among different ethnic groups. However, the report concerning the clinical outcome after radical prostatectomy (RP) in the low incidence Asian population is still limited. We aimed to compare the clinical outcome in patient treated with RP among different ethnic groups and to identify significant prognostic factors in Taiwanese patients.

Methods.?A total of 341 patients with clinical localized prostate cancer undergoing curative RP in three medical centers in Taiwan were included in this study. Ethnic group comparison was performed using the CaPSURE, SEARCH databases from United States (US) and one large European series. The Kaplan–Meier analysis and Cox proportional hazard model were used to identify significant predictors for prostate-specific antigen (PSA) recurrence.

Results.?Compared to the Caucasian white population in the US and Europe studies, the Taiwanese population have higher age at surgery and higher pre-operative PSA level. With mean and median follow-up of 39.1 months and 31.0 months (range 5–120 months), 127 men (37.2%) had PSA recurrence which was significant higher than the Western series. Significant predictors for PSA recurrence identified in the post-operative overall model were PSA level, pathological Gleason Score, pathological tumor stage and lymph node metastasis.

Conclusions.?The clinical outcome of Taiwanese male with prostate cancer post-RP appears inferior to the Western country, which is largely due to delay surgery at higher PSA level. Earlier diagnosis and treatment may improve the cancer control of RP.     

The effect of 6 months of androgen deprivation therapy on muscle and fat mass in older men with localized prostate cancer

Objective.?To evaluate body composition changes, specifically skeletal muscle mass, in men receiving androgen deprivation with luteinizing-hormone releasing hormone-agonist (LHRH-A) for prostate cancer (PCa) in comparison with healthy controls.

Design.?Retrospective analysis of body composition changes in men with prostate cancer receiving LHRH-A therapy from 2 clinical trials compared to men without prostate cancer serving as a placebo-control in another clinical trial.

Setting.?Clinical Research Center in Connecticut.

Participants.?Thirty men (> 60 years) receiving 6 months of LHRH-A therapy for PCa were compared to a healthy group of 25 men without PCa.

Measurements.?Appendicular skeletal muscle/height² (ASM/ht²), lean and fat mass were assessed by dual energy x-ray absorptiometry. Total testosterone levels were assessed by enzyme immunoassay.

Results.?At baseline, 12/30 (40%) of the treatment group and 7/25 (28%) of the control group (p = 0.11) met criteria for sarcopenia. There were no differences between control groups in ASM/ht² or lean mass. The LHRH-A group had a higher percent body fat than the control group, 29.8 ± 6.3 versus 26.3 ± 4.6 (p = 0.02). ASM/ht² and lean mass decreased in the LHRH-A group from 7.5 ± 0.9 kg to 7.3 ± 0.9 kg (?2.3% ± 0.03; p ? 0.001) and 53.5 ± 5.4 kg to 52.3 ± 5.3 kg (?2.1% ± 0.03; p ? 0.001), respectively. There was no muscle loss in the control group. At 6 months, the LHRH-A group had increased percent body fat from 29.8 ± 6.4 to 32.2 ± 5.8 (9.5% ± 0.13; p ? 0.001), whereas the control group had decreased in percent body fat from 26.6 ± 4.6 to 25.3 ± 5.0 (?3.8% ± 0.08; p = 0.02).

Conclusions.?Men undergoing LHRH-A treatment for PCa decreased appendicular skeletal muscle and lean tissue and increased body fat within 6 months of initiation of therapy. Lifestyle changes or medical interventions to minimize the effects of androgen deprivation therapy for PCa deserve investigation.     

A Welcome to the International Statistical Conferences

Criteria for assessing the effectiveness of a medical screening program are difficult to define; medical knowledge and screening procedures change rapidly, and self-selection at medical screens is unavoidable. This article discusses these and other basic issues in evaluation of medical screening programs with particular reference to results from the HIP breast cancer study. In addition, the article reviews various statistical models that describe the processes of disease and screening. The models are shown to be statistically indistinguishable in practice because of the small sample sizes typically available in medical screening trials. Finally the article suggests incorporating knowledge from clinical trials and from studies of robustness into statistical models designed to identify reasonable strategies for screening.     

Bayesian age-stratified joinpoint regression model: an application to lung and brain cancer mortality

Joinpoint regression model identifies significant changes in the trends of the incidence, mortality, and survival of a specific disease in a given population. The purpose of the present study is to develop an age-stratified Bayesian joinpoint regression model to describe mortality trend assuming that the observed counts are probabilistically characterized by the Poisson distribution. The proposed model is based on Bayesian model selection criteria with the smallest number of joinpoints that are sufficient to explain the Annual Percentage Change. The prior probability distributions are chosen in such a way that they are automatically derived from the model index contained in the model space. The proposed model and methodology estimates the age-adjusted mortality rates in different epidemiological studies to compare the trends by accounting the confounding effects of age. In developing the subject methods, we use the cancer mortality counts of adult lung and bronchus cancer, and brain and other Central Nervous System cancer patients obtained from the Surveillance Epidemiology and End Results data base of the National Cancer Institute.     

Nonparametric Comparison for Multivariate Panel Count Data

Multivariate panel count data often occur when there exist several related recurrent events or response variables defined by occurrences of related events. For univariate panel count data, several nonparametric treatment comparison procedures have been developed. However, it does not seem to exist a nonparametric procedure for multivariate cases. Based on differences between estimated mean functions, this article proposes a class of nonparametric test procedures for multivariate panel count data. The asymptotic distribution of the new test statistics is established and a simulation study is conducted. Moreover, the new procedures are applied to a skin cancer problem that motivated this study.     

不同化疗方案治疗晚期胃癌的疗效观察

目的比较FOLFOX、CF、DCFZ种化疗方案治疗晚期胃癌的效果。方法回顾分析173例分别采用FOLFOX、CF及DCF3种治疗方案的初治晚期胃癌患者：其中采用FOLFOX方案治疗71例,CF方案59例,DCF方案43例。每28天为1个疗程,至少完成2个周期的化疗后,评估患者的近期疗效和毒副反应。结果3种方案的近期疗效分别为：FOLFOX方案31．0％,CF方案27．1％,DCF方案55．8％,DCF方案疗效明显高于其他两个方案,差异有统计学意义（P〈0．01）。毒副反应主要为骨髓抑制和消化道反应,DCF方案发生几率较高,但患者均可耐受,差异无统计学意义（P〉0．05）。结论晚期胃癌患者应用DCF方案近期疗效较好,不良反应可以耐受,值得临床推广使用。     

Bounds in Competing Risks Models and the War on Cancer

In 1971, President Nixon declared war on cancer. Thirty years later, many declared this war a failure: the age‐adjusted mortality rate from cancer in 2000 was essentially the same as in the early 1970s. Meanwhile the age‐adjusted mortality rate from cardiovascular disease fell dramatically. Since the causes that underlie cancer and cardiovascular disease are likely dependent, the decline in mortality rates from cardiovascular disease may partially explain the lack of progress in cancer mortality. Because competing risks models (used to model mortality from multiple causes) are fundamentally unidentified, it is difficult to estimate cancer trends. We derive bounds for aspects of the underlying distributions without assuming that the underlying risks are independent. We then estimate changes in cancer and cardiovascular mortality since 1970. The bounds for the change in duration until death for either cause are fairly tight and suggest much larger improvements in cancer than previously estimated.     

Radon as a Tracer of Lung Changes Induced by Smoking

After smoking, exposure to radon and its progeny is the second leading cause of lung cancer. The probability of inducing lung carcinomas by inhaled radon progeny depends on the deposited radiation dose, and is significantly affected by physiological and morphometric changes induced by smoking. Due to irritation of the airways, the inhalation of cigarette smoke leads to the hyperproduction of mucus. Two concurrent processes occur: on one hand, increased production of mucus protects the target cells against radiation damage; on the other hand, in the case of long-term smokers, a chronic lung obstruction develops, causing an increase in the radiation dose to the lungs. Depending on the duration and intensity of smoking, these processes contribute to the final radiation dose with different weights. The primary objective of this study was to investigate to what extent these smoke-induced changes can modify the resulting absorbed dose of inhaled radon progeny relative to healthy nonsmokers. Since the bronchial dose depends on the degree of lung tissue damage, we have used this dose as a tool for detecting the effects of smoking on the lung epithelium. In other words, the biological effect of radon served as a tracer of changes induced by smoking.