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Nutritional and surgical aspects in prostate disorders
Abstract
Prostate disorders are commonplace in medicine, especially in older men, with prostatitis, benign prostatic hyperplasia, and prostate cancer being the most abundant pathologies. The complexity of this organ, however, turns treatment into a challenge. In this review, we aim to provide insight into the efficacy of alternative treatments, which are not normally used in conventional medicine, with a particular focus on nutrients. In order to understand why and how nutrition can be beneficial in diseases of the prostate, we give an overview of the known characteristics and features of this organ. Then, we provide a summary of the most prevalent prostate illnesses. Finally, we propose nutrition-based treatment in each of these prostate problems, based on in-depth research concerning its effects in this context, with an emphasis on surgery. Overall, we plead for an upgrade of this form of alternative treatment to a fully recognized mode of therapy for the prostate.
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Background
This practical guideline is based on the current scientific ESPEN guidelines on nutrition in cancer patients.
Methods
ESPEN guidelines have been shortened and transformed into flow charts for easier use in clinical practice. The practical guideline is dedicated to all professionals including physicians, dieticians, nutritionists and nurses working with patients with cancer.
Results
A total of 43 recommendations are presented with short commentaries for the nutritional and metabolic management of patients with neoplastic diseases. The disease-related recommendations are preceded by general recommendations on the diagnostics of nutritional status in cancer patients.
Conclusion
This practical guideline gives guidance to health care providers involved in the management of cancer patients to offer optimal nutritional care.
Background. Prostate cancer (PCa) is the second most commonly diagnosed cancer, and the sixth most common killer among men worldwide (Aubry et al., 2013). This research was motivated by the fact that PCa screening continues to be a controversial topic in the Kazakh medical community. This study aimed at description of how newly diagnosed PCa patients are managed in Pavlodar region of the Kazakhstan Republic and at presentation of a budget impact analysis (BIA) for PCa screening program. Also, we aimed to provide a comparative analysis of pricing system on medical services applied in both private and public healthcare sectors of the Kazakhstan Republic. Methods. New cases of PCa have been retrospectively analyzed for the period from January 2013 to December 2017 based on the information obtained from information system “Policlinic” maintained by the Pavlodar regional branch of the Republican Center for Electronic Health and from Cancer Registry of Pavlodar Regional Oncology Center. All data were analyzed with the help of SPSS 20.0 software. Results. The mean age of PCa patients was 68.34 years (SD = 8.559). The government of Kazakhstan invested 20,437,000 KZT (Kazakhstani tenge) in 2017 equivalently 61,188 USD—to fund a pilot study for examination of 9638 men. From 2013 to 2017, out of 49,334 men residing in Pavlodar region of Kazakhstan 1,248 men were diagnosed with prostate diseases, including 130 PCa cases. The PCa detection rate was equal to two cases per month. Only 22.8% of all PCa cases identified in the region within specified time period were revealed as a result of the government-funded PCa screening program. The average prostate cancer detection rate among the target group of Pavlodar region within the period of 5 years was equal to 0.23%. Conclusion. Based on the fact that the PCa screening program failed to enable adequate detection of new PCa cases, we would not recommend to continue this type of screening unless it is undergone careful revision and replanning.
1. Introduction
Prostate cancer (PCa) is the second most commonly diagnosed cancer, and the sixth most common killer among men worldwide [1]. With an estimated annual incidence of 903,500 cases per year, PCa causes more than 250,000 deaths annually [2–4]. The incidence of PCa varies starkly across different regions. For example, it is well-known that the incidence rate of PCa is significantly lower in Asia than in Western countries, and much higher in the developing world than in the developed world [5]. The rates of metastatic disease and deaths from PCa in Asian countries are higher than those in Western countries due to the low exposure rate to screening [6]. PCa mortality rates have steadily decreased over the past 10 years in many countries, including England, Wales, the Czech Republic and the United States, but are increasing in Eastern European countries and in some Asian countries, such as Korea [7–9]. PCa morbidity indicators have also increased over the last several years in Kazakhstan as well [10], which may be due to introduction of the screening program that started in 2013 [11].
It is estimated that in the United States alone 1.86 billion USD are spent annually on PSA testing and more than 4 billion USD are spent annually on therapies for PCa [1]. According to 2007–2009 costs of PSA-based PCa screening, the average annual PCa screening cost per beneficiary was 36 USD. The inverse relation between beneficiary’s age and screening cost was established (). Extrapolating the costs of the fee-for-service provided to Medicare beneficiaries (United States’ healthcare for people of over 65) to population nationwide, the annual costs of PCa screening to the program were 447 million USD, including 145 million USD for men aged over 75 years [12].
Economic evaluation is particularly important for preventive medicine, which holds great potential to improve healthcare, particularly in low- and middle-income countries [13]. Studies evaluating the cost-effectiveness of PSA screening have produced a wide range of results. Despite several model-based evaluations, the robust evidence to suggest cost-effectiveness is lacking [14]. A recent study based in the United States estimated that PSA screening costs 262,758 USD per life-year gained (LYG), or over 5 million USD per death avoided [15]. A systematic review reported that cost-effectiveness is in the range of 12,000 USD /LYG to 5,000 USD /LYG, which suggests that screening is more cost-effective in men aged 50–69 years as compared to men over 70 years of age [16]. Pataky et al. argue that screening for PCa with low frequency PSA testing may be cost-effective when quality of life is not considered, but all developed 14 screening strategies had a net negative effect on the Quality Adjusted Life Years (QALYs) [17]. According to Shin et al. the national Prostate-Specific-Antigen (PSA) screening in South Korea is not cost-effective [18]. Recently, a systematic review on cost-effectiveness of PCa screening was published. Once more, this study concluded that the answer to the question of whether or not screening for prostate cancer is cost-effective remains unclear. According to existing health economics research, population-wide PSA screening is costly and ineffective but still, it may be cost-effective in certain populations [19].
Studies on the cost-effectiveness of PCa screening are primarily based on developed countries’ data and relatively little is known about developing countries, especially due to the lack of large longitudinal databases [20]. The experience of Kazakhstan is interesting in this respect, since in 2013 the country launched a Prostate Cancer Screening Program which was terminated at the end of 2017. This decision could be partly attributed to the lack of reliable PCa screening system in Kazakhstan. In fact, the results of a recently published study indicate that PSA test is not a reliable method for identification of PCa among Kazakhstani patients as there was a high ratio of false-positive results for this test, which resulted in unnecessary biopsies. This 2017 study also found that the test’s sensitivity is as high as 96.61%, but the specificity is as low as 10.43% [21]. This study aimed at description of how newly diagnosed PCa patients are managed in Pavlodar region of the Kazakhstan Republic and at presentation of a budget impact analysis (BIA) for PCa screening program. Also, we aimed to provide a comparative analysis of pricing system on medical services applied in both private and public healthcare sectors of the Kazakhstan Republic.
2. Materials and Methods
In Kazakhstan, the healthcare system essentially focuses on the provision of primary care. This goes back to the Soviet days, to the Alma-Ata 1978 International Conference on Primary Healthcare, or Health for all, which emphasized the significance of primary care. This conference is famous for the adoption of the so-called Alma-Ata Declaration. Kazakhstan is currently implementing the state program for the development of healthcare system entitled “Densaulyk”, which covers the period of 2016–2019. Based on this program, the government of Kazakhstan pays particular attention to the provision of national screening programs. Concerning PCa screening, it was carried out in the period from 2013 through 2017, and covered 11 out of the 16 country regions. The country introduced government-funded serum PSA testing among men aged 50, 54, 58, 62 and 66 years. In 2013, the pilot PCa screening were initiated in East Kazakhstan, West Kazakhstan, Kyzylorda and Pavlodar regions, as well as in two cities of national significance (Almaty and Astana). In 2014, this effort was extended to Aktobe, Atyrau, Karaganda, Kostanay and North Kazakhstan regions [10]. However, since 2018, the government-funded PCa screening has been stopped due to the expansion of target age groups for breast, cervical and colorectal cancers.
All PCa screening procedures were regulated by the Order of the Ministry of Health “On approval of the Rules for conducting preventive medical examinations of target population groups” of November 2009 (N 685). According to this Order, the target population groups were men aged 50, 54, 58, 62 and 66 years not followed for prostate cancer. The primary healthcare establishments invited all men of appropriate ages by means of direct contact, phone calls or via family members/neighbors to attend the clinic for a PSA blood test. For the PCa screening within 2013–2017, 49,334 agreed to participate. According to the local health plan, in 2017 out of 20,628 men aged 50, 54, 58, 62 and 66 years, only 9,638 men took part in the Prostate Screening Program, which resulted in 46.7% response rate. Besides testing serum PSA levels by means of immunohistochemistry, the PCa screening also involved evaluation of the so-called “Prostate Health Index” (PHI) that was based on measurements of total PSA, free PSA and proPSA. The PSA cut-off for a prostate biopsy was total PSA ≥7.8 ng/ml or PHI ≥25. The actual number of men who had undergone prostate biopsy was not reported.
Pavlodar region was involved in this pilot screening program for PCa within the entire period of its implementation, which equaled five years. The region locates in North-Eastern part of Kazakhstan and has a population of 769,346 people. Of these, 49,334 men were exposed to PCa screening from January 2013 to December 2017 that was organized in primary healthcare centers throughout the region. General practitioners and nurses drove data about participants’ cases into the screening registry. Afterwards, all cancer cases identified were registered in the cancer registry by the staff from the local oncology center. We obtained this dataset and subjected it to retrospective analysis. The dataset included all prostate cancer cases that were diagnosed between January 1, 2013 and December 31, 2017 (code C61, based on the International Classification of Diseases, 10th edition). For economic analysis, we obtained the official financial documents from the Healthcare Department of Pavlodar region. Information about prices on medical services of private sector was analyzed based on the data presented on official websites of health care establishments.
All patients with verified PCa undergo treatment at governments expense. The available treatment options are detailed in the national guidelines “Cancer of the Prostate” that follow recommendations given in Clinical Practice Guidelines of the European Society for Medical Oncology (https://www.esmo.org/Guidelines/Genitourinary-Cancers/Cancer-of-the-Prostate).
2.1. Statistical Analyses
IBM SPSS Statistics version 20.0 was used for all data analyses. We computed the following variables: age, stage of the disease, year of diagnosis, place of residence and PCa cases detected out of screening program. Student’s t-test, Pearson’s chi-square test and one-way analysis of variance were applied to test for the difference. Student’s t-test was used to compare the mean values of continuous variables, like age and residence, while comparison between the mean values of variables like disease stage/year of diagnosis were conducted by the one-way analysis of variance. Chi-squared test was used to compare the categorical or nominal variables. Normally distributed data were expressed as the mean and standard deviation. Differences were considered statistically significant when .
The survey was approved by the Ethical Committee of Semey Medical University, Kazakhstan.
3. Results
Overall, there were 49,334 men who were screened for PCa within 2013–2017 by means of serum PSA measurement. Of these, 47,234 men had PSA level not exceeding 3.1 ng/ml, in 1,679 men the PSA levels ranged from 3.1 to 7.8 ng/ml, and in 421 men the serum PSA was 7.8 ng/ml and higher. There were 2.5% of men who were diagnosed with benign prostate hyperplasia or prostatis following the subsequent evaluation (Table 1).
Year
Number of patients examined for PSA
Results of PSA test
Free PSA & ProPSA
PHI 25 and above
Number of identified diseases (N40, N41)
Number of identified PCa
<3.1 ng/ml
3.1–7.8 ng/ml
>7.8 ng/ml
2–4 points according to Gleason
5–7 points according to Gleason
8–10 points according to Gleason
2013
9888
9504
331
53
129
91
196
8
5
0
2014
11666
11250
320
96
265
200
279
16
6
8
2015
9322
8877
367
78
268
151
355
4
1
2
2016
8821
8426
322
73
188
153
204
4
5
11
2017
9637
9177
339
121
185
142
214
4
6
9
Total
49334
47234
1679
421
1035
737
1248
36
23
30
Background: The incidence and mortality from prostate cancer in most native Asian populations remain low
although a gradual increase is observed over the last years.
Methods: The statistical analysis of official data on prostate cancer mortality and morbidity was performed for
the whole country and for Pavlodar Region.
Results: The increase in the incidence of prostate cancer among the population of Kazakhstan is observed,
which may be attributed to the introduction of screening program based on serum PSA. Still, the crude incidence
rates in Kazakhstan are below world indices. Over the last few years, the decreasing prostate cancer mortality is
observed that might be influenced by early diagnosis. The age-standardized incidence rates show that the majority of prostate cancer cases occur in advanced ages (70 years and older).
Conclusion: More research is needed to determine the risk factors for prostate cancer, as well as ethnic and
geographical trends for the population of Kazakhstan
Objectives:
To examine the long-term outcomes of transurethral resection of the prostate.
Methods:
We retrospectively collected the data of patients who had undergone transurethral resection of the prostate before December 2010. Patients had been evaluated by urodynamics and the International Prostate Symptom Score preoperatively, and they were re-evaluated by using the International Prostate Symptom Score at the minimum 7 years after transurethral resection of the prostate. Patients who received any treatments to improve voiding symptoms were defined as having a relapse of voiding dysfunction. The Schäfer nomogram was used to assess the degree of obstruction and detrusor contractility. We assessed the change in International Prostate Symptom Score over time depending on obstruction (Schäfer grade 3-6) versus no obstruction (Schäfer grade 0-2), and normal detrusor contractility (strong and normal) versus detrusor underactivity (weak and very weak). Relapse rates of voiding dysfunction were determined using the Kaplan-Meier method.
Results:
A total of 39 patients were included. The mean age at transurethral resection of the prostate was 69.8 years, and the mean observation period after transurethral resection of the prostate was 114 months. During the observation period, eight patients (21%) were categorized as relapse of voiding dysfunction and the mean time to relapse was 4.2 years. Patients categorized as no obstruction or detrusor underactivity had a higher recurrence rate of voiding dysfunction with a statistical significance between those with versus without obstruction. Except for patients with relapse of voiding dysfunction, improvement of the International Prostate Symptom Score was maintained over a period of 10 years after transurethral resection of the prostate.
Conclusions:
Favorable long-term symptomatic outcome after transurethral resection of the prostate is likely in patients with urodynamic obstruction. Patients without urodynamic obstruction are likely to have a relapse of voiding symptoms and require additional treatments in the long term.
Purpose of Review
To review the most up-to-date diagnosis and treatment of chronic prostatitis. We conducted a review of the literature based on the diagnosis and treatment of chronic prostatitis.
Recent Findings
The use of advanced phenotyping, links to lifestyle, and multimodal approaches has helped to enhance the treatment of chronic prostatitis and its negative effects on quality of life.
Summary
Chronic prostatitis is a common and complex condition that requires a multimodal approach to treat symptoms. Recent advances in phenotyping and risk factors help to individualize treatment and enhance treatment outcomes.
Benign prostatic hyperplasia and hypertension are common age-related comorbidities. Although the etiology of benign prostatic hyperplasia (BPH) is still largely unresolved and poorly understood, a significant age-independent association was found between BPH and hypertension, indicating a common pathophysiological factor for both diseases. It has previously been suggested that the development of essential hypertension may be related to diet-induced hyperinsulinemia. This study follows the question, whether BPH may develop due to the same mechanism, thereby explaining the well-known comorbidity of these 2 disorders. The scientific evidence presented shows that BPH and hypertension share the same pathophysiological changes, with hyperinsulinemia as the driving force. It further shows that significant dietary changes during human history cause disruption of a finely tuned metabolic balance that has evolved over millions of years of evolution: high-insulinemic food, typical of current “Western” diets, has the potential to cause hyperinsulinemia and insulin resistance, as well as an abnormally increased activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system, alterations that play a pivotal role in the pathogenesis of BPH and hypertension.
Purpose:
The clinical term "prostatitis" refers to a clinical syndrome defined by the following 4 distinct entities: acute bacterial prostatitis (category 1), chronic bacterial prostatitis (category 2), chronic prostatitis/chronic pelvic pain syndrome (category 3), and asymptomatic prostatitis (category 4) The etiology of the chronic forms is still not fully understood and choice of therapy is often debated. The objective of this systematic review is to collect evidence on the surgical treatment of the chronic form of prostatitis and to evaluate its clinical implication.
Methods:
We performed a systematic literature search and identified 6683 relevant publications, of which 16 were included in the review.
Results:
Transurethral prostate resection was performed in 110 patients; 78 patients (70%) were reported as "cured", 16 patients (15%) as improved, and 16 patients (15%) as unchanged. Radical prostatectomy was performed in 21 patients; a full resolution of prostatitis related symptoms was reported for 20 patients (95%). No increased rates of complications or unusual complications were noted.
Conclusions:
Surgical therapy of chronic bacterial prostatitis or chronic pelvic pain syndrome might be a viable option; however, since little evidence is currently available and no randomized controlled trials have been conducted, the presently available data does not provide a base for clinical decisions.
A disease can be defined as an abnormal anatomy (pathology) and/or function (physiology) that may cause harm to the body. In clinical benign prostatic hyperplasis (BPH), the abnormal anatomy is prostate adenoma/adenomata, resulting in a varying degree of benign prostatic obstruction (BPO) that may cause harm to the bladder or kidneys. Thus clinical BPH can be defined as such and be differentiated from other less common causes of male lower urinary tract symptoms. Diagnosis of the prostate adenoma/adenomata (PA) can be made by measuring the intravesical prostatic protrusion (IPP) and prostate volume (PV) with non-invasive transabdominal ultrasound (TAUS) in the clinic. The PA can then be graded (phenotyped) according to IPP and PV. Multiple studies have shown a good correlation between IPP/PV and BPO, and therefore progression of the disease. The severity of the disease clinical BPH can be classified into stages from stage I to IV for further management. The classification is based on the effect of BPO on bladder functions, namely that of emptying, normal if post-void residual urine (PVRU) 100 mL. The effect of BPO on quality of life (QoL) can be assessed by the QoL index, with a score ≥3 considered bothersome. Patients with no significant obstruction and no bothersome symptoms would be stage I; those with no significant obstruction but has bothersome symptoms (QoL ≥ 3) would be stage II; those with significant obstruction (PVRU > 100 mL; or MVV
Early oral feeding is the preferred mode of nutrition for surgical patients. Avoidance of any nutritional therapy bears the risk of underfeeding during the postoperative course after major surgery. Considering that malnutrition and underfeeding are risk factors for postoperative complications, early enteral feeding is especially relevant for any surgical patient at nutritional risk, especially for those undergoing upper gastrointestinal surgery. The focus of this guideline is to cover both nutritional aspects of the Enhanced Recovery After Surgery (ERAS) concept and the special nutritional needs of patients undergoing major surgery, e.g. for cancer, and of those developing severe complications despite best perioperative care. From a metabolic and nutritional point of view, the key aspects of perioperative care include:
Background:
The purpose of this study was to identify risk factors for abscess formation in acute bacterial prostatitis, and to compare treatment outcomes between abscess group and non-abscess group.
Methods:
This is a multicenter, retrospective cohort study. All patients suspected of having an acute prostatic infection underwent computed tomography or transrectal ultrasonography to discriminate acute prostatic abscesses from acute prostatitis without abscess formation.
Results:
A total of 31 prostate abscesses were reviewed among 142 patients with acute prostatitis. Univariate analysis revealed that symptom duration, diabetes mellitus and voiding disturbance were predisposing factors for abscess formation in acute prostatitis. However, diabetes mellitus was not related to prostate abscess in multivariate analysis. Patients with abscesses <20 mm in size did not undergo surgery and were cured without any complications. In contrast, patients with abscesses >20 mm who underwent transurethral resection had a shorter duration of antibiotic treatment than did those who did not have surgery. Regardless of surgical treatment, both the length of hospital stay and antibiotic treatment were longer in patients with prostatic abscesses than they were in those without abscesses. However, the incidence of septic shock was not different between the two groups. A wide spectrum of microorganisms was responsible for prostate abscesses. In contrast, Escherichia coli was the predominant organism responsible for acute prostatitis without abscess.
Conclusion:
Imaging studies should be considered when patients with acute prostatitis have delayed treatment and signs of voiding disturbance. Early diagnosis is beneficial because prostatic abscesses require prolonged treatment protocols, or even require surgical drainage. Surgical drainage procedures such as transurethral resection of the prostate were not necessary in all patients with prostate abscesses. However, surgical intervention may have potential merits that reduce the antibiotic exposure period and enhance voiding function in patients with prostatic abscess.
Recent lineage tracing studies showed that the prostate basal and luminal cells in adult mice are two independent lineages under the physiological condition, but basal cells are capable of generating luminal progenies during bacterial infection-induced prostatitis. Because acute bacterial infection in human prostate tissues is relatively rare, the disease relevance of the bacterial infection-induced basal-to-luminal differentiation is uncertain. Herein we employ a high fat diet-induced sterile prostate inflammation model to determine whether basal-to-luminal differentiation can be induced by inflammation irrespective of the underlying etiologies. A K14-CreER model and a fluorescent report line are utilized to specifically label basal cells with the green fluorescent protein. We show that high fat diet promotes immune cell infiltration into the prostate tissues and basal-to-luminal differentiation. Increased cell proliferation accompanies basal-to-luminal differentiation, suggesting a concurrent regulation of basal cell proliferation and differentiation. This study demonstrates that basal-to-luminal differentiation can be induced by different types of prostate inflammation evolved with distinct etiologies. Finally, high fat diet also accelerates initiation and progression of prostatic intraepithelial neoplasia that are originated from basal cells with loss-of-function of the tumor suppressor Pten. Because prostate cancer originated from basal cells tends to be invasive, our study also provides an alternative explanation for the association between obesity and aggressive prostate cancer.
Findings from epidemiologic studies examining associations of serum retinol and carotenoids with prostate cancer risk have been inconsistent. This case-control study nested in the Prostate Cancer Prevention Trial evaluated associations of serum retinol and carotenoids with total, low- and high-grade prostate cancer risk in a highly-screened study population.
We used logistic regression adjusting for age, family history of prostate cancer, race, BMI and serum cholesterol to estimate odds ratios (OR) and 95% confidence intervals (CI) of prostate cancer by quartiles of serum retinol and carotenoids, separately in the placebo (975 cases/1009 frequency-matched controls) and finasteride (708 cases/743 frequency-matched controls) arms of the trial.
Serum retinol concentrations were associated with increased risk of total prostate cancer [OR (95% CI) comparing the highest quartile of serum retinol to the lowest: 1.30 (1.00, 1.68)] and high-grade prostate cancer [OR (95% CI): 1.74 (1.14, 2.68)] in the placebo arm of the trial only. Also in the placebo arm, there was a moderate positive association of α-carotene with risk of total prostate cancer [OR (95% CI): 1.32 (1.01, 1.73)]. None of the other carotenoids was associated with prostate cancer risk in the placebo arm. No associations were observed for retinol and carotenoids in the finasteride arm.
In the placebo arm of this prospective study, high serum retinol and α-carotene concentrations were associated with increased risk of total and high-grade prostate cancers.
Men with higher levels of serum retinol and α-carotene may be at increased risk for prostate cancer.
Copyright © 2015, American Association for Cancer Research.
Metformin is derived from galegine, a natural ingredient, and recent studies have suggested that metformin could enhance the antitumor effects of hormone ablative therapy or chemotherapy and reduce prostate cancer-specific mortality. Zyflamend is a combination of herbal extracts that reduces inflammation and comprises turmeric, holy basil, green tea, oregano, ginger, rosemary, Chinese goldthread, hu zhang, barberry, and basil skullcap. We propose a maintenance regimen with metformin and/or Zyflamend that targets cancer stem cells and the tumor microenvironment to keep the cancer dormant and prevent it from activation from dormancy. Herein, we report the clinical course of four patients who experienced a clinical response after treatment with metformin and/or Zyflamend.
Prostate cancer (PCa) remains a leading cause of mortality in US men and the prevalence continues to rise world-wide especially in countries where men consume a ‘Western-style’ diet. Epidemiologic, preclinical and clinical studies suggest a potential role for dietary intake on the incidence and progression of PCa. 'This minireview provides an overview of recent published literature with regard to nutrients, dietary factors, dietary patterns and PCa incidence and progression. Low carbohydrates intake, soy protein, omega-3 (w-3) fat, green teas, tomatoes and tomato products and zyflamend showed promise in reducing PCa risk or progression. A higher saturated fat intake and a higher β-carotene status may increase risk. A ‘U’ shape relationship may exist between folate, vitamin C, vitamin D and calcium with PCa risk. Despite the inconsistent and inconclusive findings, the potential for a role of dietary intake for the prevention and treatment of PCa is promising. The combination of all the beneficial factors for PCa risk reduction in a healthy dietary pattern may be the best dietary advice. This pattern includes rich fruits and vegetables, reduced refined carbohydrates, total and saturated fats, and reduced cooked meats. Further carefully designed prospective trials are warranted.
Studies have reported inconsistent results concerning the existence of associations of folate intake and serum folate levels with prostate cancer risk. This study sought to summarise the evidence regarding these relationships using a dose-response meta-analysis approach.
In January 2014, we performed electronic searches of PubMed, Embase, and the Cochrane Library to identify studies examining the effect of folate on the incidence of prostate cancer. Only prospective studies that reported effect estimates with 95% confidence intervals (CIs) of the incidence of prostate cancer for more than 2 categories of folate were included.
Overall, we included 10 prospective studies reporting data on 202,517 individuals. High dietary folate intake had little or no effect on prostate cancer risk (risk ratio [RR] = 1.02; 95%CI = 0.95-1.09; P = 0.598). The dose-response meta-analysis suggested that a 100 mug per day increase in dietary folate intake has no significant effect on the risk of prostate cancer (RR = 1.01; 95%CI = 0.99-1.02; P = 0.433). However, high serum folate levels were associated with an increased risk of prostate cancer (RR = 1.21; 95%CI = 1.05-1.39; P = 0.008). The dose-response meta-analysis indicated that a 5 nmol/L increment of serum folate levels was also associated with an increased risk of prostate cancer (RR = 1.04; 95%CI = 1.00-1.07; P = 0.042).
Our study indicated that dietary folate intake had little or no effect on prostate cancer risk. However, increased serum folate levels have potentially harmful effects on the risk of prostate cancer.
Background
Men with biochemical recurrence (BCR) of prostate cancer are typically observed or treated with androgen deprivation therapy. Non-hormonal, non-toxic treatments to slow the rise of PSA are desirable. We studied a combination herbal supplement, Prostate Health Cocktail (PHC), in prostate cancer cell lines and in a population of men with BCR.
Methods
PC3, LAPC3, and LNCaP cells were incubated with increasing concentrations of PHC suspension. Men previously treated for prostate cancer with surgery, radiation, or both with rising PSA but no radiographic metastases were treated with 3 capsules of PHC daily; the primary endpoint was 50% PSA decline. Circulating tumor cells (CTCs) were identified using parylene membrane filters.
Results
PHC showed a strong dose-dependent anti-proliferative effect in androgen-sensitive and independent cell lines in vitro and suppression of androgen receptor expression. 40 eligible patients were enrolled in the clinical trial. Median baseline PSA was 2.8 ng/mL (1.1-84.1) and 15 men (38%) had a PSA decline on study (1%-55% reduction) ; 25 (62%) had rising PSA on study. The median duration of PSA stability was 6.4 months. Two patients had grade 2/3 transaminitis; the only other grade 2 toxicities were hyperglycemia, hypercalcemia and flatulence. There were no significant changes in testosterone or dihydrotestosterone. CTCs were identified in 19 men (47%).
Conclusion
Although the primary endpoint was not met, Prostate Health Cocktail was well tolerated and was associated with PSA declines and stabilization in a significant number of patients. This is the first report of detecting CTCs in men with BCR prostate cancer. Randomized studies are needed to better define the effect of PHC in men with BCR.
Exploring natural plant products as an option to find new chemical entities as anticancer agents is one of the fastest growing areas of research. Recently, in the last decade, essential oils (EOs) have been under study for their use in cancer therapy and the present review is an attempt to collect and document the available studies indicating EOs and their constituents as anticancer agents. This review enlists nearly 130 studies of EOs from various plant species and their constituents that have been studied so far for their anticancer potential and these studies have been classified as
in vitro
and
in vivo
studies for EOs and their constituents. This review also highlights in-depth various mechanisms of action of different EOs and their constituents reported in the treatment strategies for different types of cancer. The current review indicates that EOs and their constituents act by multiple pathways and mechanisms involving apoptosis, cell cycle arrest, antimetastatic and antiangiogenic, increased levels of reactive oxygen and nitrogen species (ROS/RNS), DNA repair modulation, and others to demonstrate their antiproliferative activity in the cancer cell. The effect of EOs and their constituents on tumour suppressor proteins (p53 and Akt), transcription factors (NF-
κ
B and AP-1), MAPK-pathway, and detoxification enzymes like SOD, catalase, glutathione peroxidase, and glutathione reductase has also been discussed.
Epidemiological studies that have examined the association of blood α-tocopherol and γ-tocopherol (the principal bioactive form of vitamin E) levels with the risk of prostate cancer have yielded inconsistent results. In addition, a quantitative assessment of published studies is not available.
In this meta-analysis, relevant studies were sought by a search of the PubMed and Embase databases for articles published up to October 2013, with no restrictions. Bibliographies from retrieved articles also were scoured to find further eligible studies. Prospective studies that reported adjusted relative risk (RR) estimates with 95% confidence intervals (CIs) for the association between blood tocopherol levels and the risk of prostate cancer were included. Nine nested case-control studies involving approximately 370,000 participants from several countries were eligible. The pooled RRs of prostate cancer for the highest versus lowest category of blood α-tocopherol levels were 0.79 (95% CI: 0.68-0.91), and those for γ-tocopherol levels were 0.89 (95% CI: 0.71-1.12), respectively. Significant heterogeneity was present among the studies in terms of blood γ-tocopherol levels (p = 0.008) but not in terms of blood α-tocopherol levels (p = 0.33). The risk of prostate cancer decreased by 21% for every 25-mg/L increase in blood α-tocopherol levels (RR: 0.79; 95% CI: 0.69-0.91).
Blood α-tocopherol levels, but not γ-tocopherol levels, were inversely associated with the risk of prostate cancer in this meta-analysis.
Purpose: Data from epidemiological and experimental studies suggest that dietary protein intake may play a role in inhibiting prostate and breast cancer by modulating the IGF/AKT/mTOR pathway. In this study we investigated the effects of diets with different protein content or quality on prostate and breast cancer.
Experimental Design: To test our hypothesis we assessed the inhibitory effect of protein diet restriction on prostate and breast cancer growth, serum PSA and IGF-1 concentrations, mTOR activity and epigenetic markers, by using human xenograft cancer models.
Results: Our results showed a 70% inhibition of tumor growth in the castrate-resistant LuCaP23.1 prostate cancer model and a 56% inhibition in the WHIM16 breast cancer model fed with a 7% protein diet when compared to an isocaloric 21% protein diet. Inhibition of tumor growth correlated, in the LuCaP23.1 model, with decreased serum PSA and IGF-1 levels, down-regulation of mTORC1 activity, decreased cell proliferation as indicated by Ki67 staining, and reduction in epigenetic markers of prostate cancer progression, including the histone methyltransferase EZH2 and the associated histone mark H3K27me3. In addition, we observed that modifications of dietary protein quality, independently of protein quantity, decreased tumor growth. A diet containing 20% plant protein inhibited tumor weight by 37% as compared to a 20% animal dairy protein diet.
Conclusions: Our findings suggest that a reduction in dietary protein intake is highly effective in inhibiting tumor growth in human xenograft prostate and breast cancer models, possibly through the inhibition of the IGF/AKT/mTOR pathway and epigenetic modifications.
Objectives:
To provide an update on novel minimally invasive LUTS/BPH treatments in a non-systematic review. To define potential target populations for the various new minimally invasive treatments.
Methods:
Recent literature, meta-analyses and guideline recommendations for aquablation (AquaBeam® ), water vapour thermal therapy (Rezūm® ), prostate artery embolization (PAE), prostatic urethral lift (UroLift® ) and the nitinol butterfly-like stent (i-TIND® ) were reviewed.
Results:
Procedures that can be performed on an outpatient basis (Rezūm® , PAE, UroLift® and i-TIND® ) are not an alternative for the standard patient requiring BPH surgery. Their effect on uroflow, PVR or bladder outlet obstruction is less pronounced than that of TURP. Yet, these options appear to be valuable for those patients unfit for surgery, men who want to avoid medical therapy in general or those who want to avoid sexual side effects associated with medical therapy or standard BPH surgery (e.g. TURP). Aquablation is the first successfully operationalized robotic resection system, especially for patients with prostates above 50 gm in size. Nevertheless, long-term data are necessary for all novel, minimally invasive treatments.
Conclusions:
Better designed clinical trials, a clearer definition of target populations and a more realistic marketing allow a better characterisation of novel minimally invasive therapies for LUTS/BPH. It is hoped that some of these novel devices will stand the test of time, in contrast to the vast majority of their predecessors.
Background:
and aims: Benign Prostatic hyperplasia (BPH) is an important public health problem. Roughly half of all men will suffer from BPH related symptoms later in life. The prostate gland, a hormone dependent part of the male reproductive system, is susceptible to internal and external disruptions of regulatory systems. We attempt in this paper to collect available evidence on influence of lifestyle modifications, and naturally occurring substances, plants, micronutrients and supplements on BPH symptoms.
Methods:
Systematic review was performed within the MEDLINE database and Cochrane Library Central Search using a combination of Medical Subject Headings (MeSH) and keywords.
Results:
Moderate exercise and the type and amount of protein intake have a considerable influence on BPH symptoms. The intake of zinc and vitamin D also positively influence BPH symptoms, and so do certain supplements, such as saw palmetto, cemilton and pygeum extracts.
Conclusions:
Lifestyle changes, diet modification and certain nutritional supplements can favorably influence BPH symptoms.
Purpose:
To review the literature and provide recommendations on diet and lifestyle considerations in patients with prostate cancer using evidence from randomized controlled trials (RCTs) with additional considerations based on observational evidence.
Materials and methods:
We initiated our search on ClinicalTrials.gov combining the term "prostate cancer" with a variety of diet and lifestyle factors. We then supplemented our summary of publications from registered trials by including other publications available on Pubmed.
Results:
There is a well-established benefit of exercise for improving functional outcomes and pelvic floor muscle training for improving treatment-related adverse effects. Multimodality interventions that integrate several factors (e.g., low-saturated fat, plant-based, whole-food diets with exercise, and stress reduction) appear to have the most clinically significant benefit for patients with prostate cancer. Ongoing multimodality interventions are including the efficacy of implementation strategies as observed outcomes. Limited RCT evidence suggests a clinically significant benefit for guided imagery/progressive muscle relaxation, Pilates, and lycopene-rich diets and a modest benefit for green tea, qigong, massage, and avoidance of nonprescribed vitamin and mineral supplements. Observational and single arm trial evidence indicates a need for further exploration of acupuncture, coffee, cruciferous vegetables, fish, Larrea tridentata, mushrooms, and vegetable-derived fats and avoidance of eggs, dairy, poultry with skin, processed red meat, and saturated fat. Published trials suggest no benefit from hypnosis, milk thistle, pomegranate, soy, or omega-3 fatty acid supplementation.
Conclusions:
Our search demonstrated that most diet and lifestyle factors identified from observational studies have limited data from RCTs. Few items have shown early evidence of benefit. The best recommendation for patients with prostate cancer is to form a habit of wellness through healthy eating, aerobic and resistance exercise, and psychological well-being. Future trial development should consider how interventions can be implemented into real world practice.
Benign prostatic hyperplasia (BPH) is a common condition in aging men that is frequently associated with troublesome lower urinary tract symptoms (LUTS). The American Urologic Association Symptom Index is a validated, self-administered tool that is used to diagnose LUTS, guide initial treatment, and assess treatment response. Watchful waiting is an option for men with mild symptoms. Pharmacologic treatment includes alpha-adrenergic blockers and 5-alpha reductase inhibitors. There is no evidence to support the use of herbal supplements in the treatment of LUTS. Surgical therapy is effective and indicated for men with complications from BPH or who fail medical therapy.
The therapeutic landscape of prostate cancer has been transformed over the last decade by new therapeutics, advanced functional imaging, next-generation sequencing, and better use of existing therapies in early-stage disease. Until 2004, progression on androgen deprivation therapy for metastatic disease was treated with the addition of secondary hormonal manipulation; in the last decade, six systemic agents have been approved for the treatment of castration-resistant prostate cancer. We review clinical trials and survival benefit for these therapies and assess how the understanding of the disease shifted as these therapies were developed. We also discuss advances in noncastrate disease states, identification of biomarkers for prognosis and treatment selection, and opportunities in locoregional therapy to delay androgen deprivation therapy.
Background:
Malnutrition and dehydration are widespread in older people, and obesity is an increasing problem. In clinical practice, it is often unclear which strategies are suitable and effective in counteracting these key health threats.
Aim:
To provide evidence-based recommendations for clinical nutrition and hydration in older persons in order to prevent and/or treat malnutrition and dehydration. Further, to address whether weight-reducing interventions are appropriate for overweight or obese older persons.
Methods:
This guideline was developed according to the standard operating procedure for ESPEN guidelines and consensus papers. A systematic literature search for systematic reviews and primary studies was performed based on 33 clinical questions in PICO format. Existing evidence was graded according to the SIGN grading system. Recommendations were developed and agreed in a multistage consensus process.
Results:
We provide eighty-two evidence-based recommendations for nutritional care in older persons, covering four main topics: Basic questions and general principles, recommendations for older persons with malnutrition or at risk of malnutrition, recommendations for older patients with specific diseases, and recommendations to prevent, identify and treat dehydration. Overall, we recommend that all older persons shall routinely be screened for malnutrition in order to identify an existing risk early. Oral nutrition can be supported by nursing interventions, education, nutritional counseling, food modification and oral nutritional supplements. Enteral nutrition should be initiated if oral, and parenteral if enteral nutrition is insufficient or impossible and the general prognosis is altogether favorable. Dietary restrictions should generally be avoided, and weight-reducing diets shall only be considered in obese older persons with weight-related health problems and combined with physical exercise. All older persons should be considered to be at risk of low-intake dehydration and encouraged to consume adequate amounts of drinks. Generally, interventions shall be individualized, comprehensive and part of a multimodal and multidisciplinary team approach.
Conclusion:
A range of effective interventions is available to support adequate nutrition and hydration in older persons in order to maintain or improve nutritional status and improve clinical course and quality of life. These interventions should be implemented in clinical practice and routinely used.
Prostate problems can be divided into three general categories: (1) prostatitis, (2) benign prostatic hyperplasia (BPH), and (3) prostate cancer.
The human prostate is the largest male accessory gland whose main function is to produce alkaline seminal fluid which neutralises the vaginal acidity, prolonging the lifespan of sperm during reproduction. It is also the cause of two common pathological conditions—benign prostatic hyperplasia (BPH) and prostate cancer (PCa). BPH is the main condition that accounts for male patients presenting with troublesome lower urinary tract symptoms (LUTS). Despite BPH and PCa being separate conditions, patients—predominantly those from the ageing population—can present with both diseases concomitantly. This is especially true in the larger prostates. PCa is a broad disease with many phenotypical variants and even within an individual, it is not homogenous in its histological features. Despite much work there is much still to be understood about the aetiology, physiology and pathology of these disorders, particularly in patients with larger prostates.
Tocotrienols, members of the vitamin E family, have three unsaturated bonds in their side chains. Recently, it has been suggested the biological effects of tocotrienols may differ from that of tocopherols. Several in vitro studies have shown that tocotrienols have stronger anti-cancer effects than tocopherols. VCaP cell line used in this study is from a vertebral bone metastasis from a patient with prostate cancer. Eight-week-old male NCr(−/−) nude mice were subcutaneously injected with VCaP-luc cells in matrigel and then administered a tocotrienol mixture for 8 weeks. The tocotrienol mixture inhibited the growth of human prostate tumor xenografts in a dose-dependent manner. The concentrations of tocotrienols and their metabolites were significantly increased in treatment groups. Tocotrienols inhibited prostate tumor growth by suppressing cell proliferation, which was associated with the induction of the cyclin-dependent kinase (CDK) inhibitors p21 and p27. Additionally, tocotrienol treatment was associated with elevated H3K9 acetylation levels at proximal promoter regions of p21 and p27 and with decreased expression of histone deacetylases. Tocotrienols inhibited human prostate tumor growth, associated with up-regulation of the CDK inhibitors p21 and p27. Elevated expression of p21 and p27 could be partly due to the suppressed expression of HDACs.
Background:
Preclinical and clinical studies suggest that a fish oil-based diet may play a role in delaying the progression of prostate cancer through a number of different mechanisms involving inflammatory pathways. Given the importance of tumor-associated macrophages (TAMs) in carcinogenesis, we hypothesized that a fish oil-based diet will inhibit TAM infiltration and delay the growth of prostate cancer.
Methods:
Androgen sensitive mouse prostate cancer (MycCaP) allograft tumors were grown in fully immunocompetent FVB mice fed a high- fat fish oil (omega-3) or corn oil (omega-6) diet. Gene expression of markers for immune cell populations, cytokines, chemokines, and signaling pathways were determined by real-time PCR and western blot in tumor tissue. Cell proliferation and apoptosis in vitro were measured by MTS assay and flow cytometry.
Results:
Tumor volumes were significantly smaller in mice in ω-3 versus the ω-6 group (P = 0.048). Gene expression of markers for M1 and M2 macrophages (F4/80, iNOS, ARG1), associated cytokines (IL-6, TNF alpha, IL-10), and the chemokine CCL-2 were also lower in the omega-3 group. Correlative in vitro studies were performed in M1 and M2 polarized macrophages and mirrored the in vivo findings. Dietary fish oil and in vitro omega-3 fatty acid administration reduced protein expression of transcription factors in the nuclear factor kappa B pathway leading to a significant decrease in gene expression of downstream targets (Bcl-2, BCL-XL, XIAP, survivin) in MycCap cells.
Conclusions:
These findings underscore the potential of fish oil in modulating the clinical course of human prostate cancer through the immune system. Further preclinical and clinical studies are warranted evaluating fish oil-based therapies for inhibiting the recruitment and function of M1 and M2 tumor infiltrating macrophages. Prostate 9999: 1-10, 2016. © 2016 Wiley Periodicals, Inc.
Objective:
To evaluate the evidence from randomised trials for the efficacy and safety of phytotherapeutic interventions in the management of biochemically recurrent (BCR) prostate cancer, indicated by prostate-specific antigen (PSA) progression, numbers progressing to/time to initiation of androgen-deprivation therapy or salvage therapy.
Patients and methods:
MEDLINE (Ovid), EMBASE (Ovid), AMED (Ovid), CINAHL (EBSCO) and the Cochrane Library databases were searched. Clinical trials investigating phytotherapeutic interventions as dietary supplements or dietary components, including multi-component herbal formulations, in men with BCR prostate cancer were located. Eight of nine authors contacted for further information responded. Methodological quality was assessed using the Cochrane Collaboration's risk of bias assessment tool. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for reporting systematic reviews was followed.
Results:
Of 23 full-text articles assessed for eligibility, five met the criteria for inclusion. Two studies were placebo controlled; two were active control trials; and one a high-/low-dose trial. The interventions were administered as isolated phytochemicals (sulphoraphane), phytotherapeutic extracts [Pomi-T (pomegranate, turmeric, green tea and broccoli sprout extract), soy, lycopene, and POMx (pomegranate extract)], or plant-derived dietary items (soy and lycopene). All studies found serum PSA levels to stabilise, decrease or rise more slowly in a significant number of men, and three studies reported stabilising or lengthening of PSA-doubling time. Studies were generally of good quality, but sample sizes were predominantly small, and durations short.
Conclusions:
High-quality studies in this area are lacking. Sulphoraphane, lycopene, soy isoflavones, POMx, and Pomi-T are safe and well tolerated. There is limited evidence that they can affect PSA dynamics. No recommendation can be made for the use of these agents in managing prostate cancer morbidity and mortality until high-quality, fully powered studies are available. Recommendations are made for improving reproducibility and translation of findings with regard to study population, study endpoints, design, and the reporting of phytotherapeutic interventions.
Acute bacterial prostatitis is an acute infection of the prostate gland that causes pelvic pain and urinary tract symptoms, such as dysuria, urinary frequency, and urinary retention, and may lead to systemic symptoms, such as fevers, chills, nausea, emesis, and malaise. Although the true incidence is unknown, acute bacterial prostatitis is estimated to comprise approximately 10% of all cases of prostatitis. Most acute bacterial prostatitis infections are community acquired, but some occur after transurethral manipulation procedures, such as urethral catheterization and cystoscopy, or after transrectal prostate biopsy. The physical examination should include abdominal, genital, and digital rectal examination to assess for a tender, enlarged, or boggy prostate. Diagnosis is predominantly made based on history and physical examination, but may be aided by urinalysis. Urine cultures should be obtained in all patients who are suspected of having acute bacterial prostatitis to determine the responsible bacteria and its antibiotic sensitivity pattern. Additional laboratory studies can be obtained based on risk factors and severity of illness. Radiography is typically unnecessary. Most patients can be treated as outpatients with oral antibiotics and supportive measures. Hospitalization and broad-spectrum intravenous antibiotics should be considered in patients who are systemically ill, unable to voluntarily urinate, unable to tolerate oral intake, or have risk factors for antibiotic resistance. Typical antibiotic regimens include ceftriaxone and doxycycline, ciprofloxacin, and piperacillin/tazobactam. The risk of nosocomial bacterial prostatitis can be reduced by using antibiotics, such as ciprofloxacin, before transrectal prostate biopsy.
Vitamin A constituents include retinal, which plays a role in vision, and retinoic acid (RA), which has been used in the therapy of human acute promyelocytic leukemia. However, the effects on cancer of retinol and its ester, retinyl palmitate (RP) are not known well. In the current study, we examined the effects of these agents on proliferation and adhesion of various cancer cells. Retinol exhibited dose-dependent inhibition of the proliferation of human refractory and prostate cancer cells, while RA and RP showed little or no effect. In contrast, RA inhibited the growth of human breast cancer cells to a greater extent than retinol at low concentrations, but not at high concentrations. Retinol suppressed adhesion of refractory and prostate cancer cells to a greater extent than RA, while it suppressed adhesion of breast cancer cells as well as RA and of JHP-1 cells less effectively than RA. These results indicate that retinol is a potent suppressor of cancer cell growth and adhesion, which are both linked to metastasis and tumor progression. Retinol might be useful for the clinical treatment of cancer.
Tocopherols, the major forms of vitamin E, exist as alpha-tocopherol (α-T), β-T, γ-T and δ-T. The cancer preventive activity of vitamin E is suggested by epidemiological studies, but recent large-scale cancer prevention trials with high dose of α-T yielded disappointing results. Our hypothesis that other forms of tocopherols have higher cancer preventive activities than α-T was tested, herein, in a novel prostate carcinogenesis model induced by 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP), a dietary carcinogen, in the CYP1A-humanized (hCYP1A) mice. Treatment of hCYP1A mice with PhIP (200mg/kg b.w., i.g.) induced high percentages of mouse prostatic intraepithelial neoplasia (mPIN), mainly in the dorsolateral glands. Supplementation with a γ-T-rich mixture of tocopherols (γ-TmT, 0.3% in diet) significantly inhibited the development of mPIN lesions and reduced PhIP-induced elevation of 8-oxo-deoxyguanosine, COX-2, nitrotyrosine, Ki-67 and p-AKT, and the loss of PTEN and Nrf2. Further studies with purified δ-T, γ-T or α-T (0.2% in diet) showed that δ-T was more effective than γ-T or α-T in preventing mPIN formations and p-AKT elevation. These results indicate that γ-TmT and δ-T could be effective preventive agents of prostate cancer.
Background:
Individual studies have suggested that circulating carotenoids, retinol, or tocopherols may be associated with prostate cancer risk, but the studies have not been large enough to provide precise estimates of associations, particularly by stage and grade of disease.
Objective:
The objective of this study was to conduct a pooled analysis of the associations of the concentrations of 7 carotenoids, retinol, α-tocopherol, and γ-tocopherol with risk of prostate cancer and to describe whether any associations differ by stage or grade of the disease or other factors.
Design:
Principal investigators of prospective studies provided individual participant data for prostate cancer cases and controls. Risk by study-specific fifths of each biomarker was estimated by using multivariable-adjusted conditional logistic regression in matched case-control sets.
Results:
Data were available for up to 11,239 cases (including 1654 advanced stage and 1741 aggressive) and 18,541 controls from 15 studies. Lycopene was not associated with overall risk of prostate cancer, but there was statistically significant heterogeneity by stage of disease, and the OR for aggressive disease for the highest vs. the lowest fifth of lycopene was 0.65 (95% CI: 0.46, 0.91; P-trend = 0.032). No other carotenoid was significantly associated with overall risk of prostate cancer or with risk of advanced-stage or aggressive disease. For retinol, the OR for the highest vs. the lowest fifth was 1.13 (95% CI: 1.04, 1.22; P-trend = 0.015). For α-tocopherol, the OR for the highest vs. the lowest fifth was 0.86 (95% CI: 0.78, 0.94; P-trend < 0.001), with significant heterogeneity by stage of disease; the OR for aggressive prostate cancer was 0.74 (95% CI: 0.59, 0.92; P-trend = 0.001). γ-Tocopherol was not associated with risk.
Conclusions:
Overall prostate cancer risk was positively associated with retinol and inversely associated with α-tocopherol, and risk of aggressive prostate cancer was inversely associated with lycopene and α-tocopherol. Whether these associations reflect causal relations is unclear.
We hypothesized that soy phytochemicals may have immunomodulatory properties that may impact prostate carcinogenesis and progression. A randomized, phase II trial was conducted in 32 prostate cancer patients with asymptomatic biochemical recurrence but no measurable disease on standard staging studies. Patients were randomized to 2 slices of soy bread (34 mg isoflavones/slice) or soy bread containing almond powder daily as a source of β-glucosidase. Flow cytometry and bioplex assays were used to measure cytokines or immune cell phenotype in blood at baseline (day 0) and following intervention (day 56). Adequate blood samples were available at enrollment and day 56 and evaluated. Multiple plasma cytokines and chemokines were significantly decreased on Day 56 versus baseline. Subgroup analysis indicated reduced Th1 (p=0.028) and MDSC-associated cytokines (p=0.035). Th2 and Th17 cytokines were not significantly altered. Phenotypic analysis revealed no change in CD8+ or CD4+ T cells, but showed increased CD56+ NK cells (p=0.038). The percentage of cells with a T regulatory cell phenotype (CD4+CD25+FoxP3+) were significantly decreased after 56 days of soy bread (p=0.0136). Significantly decreased monocytic (CD33+HLADRnegCD14+) MDSC were observed in patients consuming soy bread (p=0.0056). These data suggest that soy bread modulates systemic soluble and cellular biomarkers relevant to immunomodulation consistent with limiting inflammation and suppression of MDSCs. Additional studies to elucidate impact on the carcinogenic process or as a complement to immune-based therapy are required.
Copyright © 2015, American Association for Cancer Research.
Although men presenting with clinically localized prostate cancer (PrCA) often are treated with radical prostatectomy or radiation therapy with curative intent, about 25-40% develop biochemically recurrent PrCA within 5 years of treatment, which has no known cure. Studies suggest that carotenoid and tocopherol intake may be associated with PrCA risk and progression. We examined plasma carotenoid and tocopherol levels in relation to prostate-specific antigen (PSA) levels among men with PSA-defined biochemical recurrence of PrCA.
Data analyzed were from a 6-month diet, physical activity and stress-reduction intervention trial conducted in South Carolina among biochemically recurrent PrCA patients (n=39). Plasma carotenoids and tocopherol levels were measured using high-performance liquid chromatography (HPLC). Linear regression was used to estimate least-square means comparing PSA levels of men with high versus low carotenoid/tocopherol levels, adjusting for covariates.
After adjusting for baseline PSA level, plasma cis-lutein/zeaxanthin level at 3 months was related inversely to PSA level at 3 months (P=0.0008), while α-tocopherol (P=0.01), β-cryptoxanthin (P=0.01), and all-trans-lycopene (P=0.004) levels at 3 months were related inversely to PSA levels at 6-months. Percent increase in α-tocopherol and trans-β-carotene levels from baseline to month 3 were associated with lower PSA levels at 3 and 6 months. Percent increase in β-cryptoxanthin, cis-lutein/zeaxanthin and all-trans-lycopene were associated with lower PSA levels at 6 months only.
Certain plasma carotenoids and tocopherols were related inversely to PSA levels at various timepoints, suggesting that greater intake of foods containing these micronutrients might be beneficial to men with PSA-defined PrCA recurrence.
Copyright © 2015. Published by Elsevier Ltd.
Background
Controversies remain over the safety and efficacy of vitamin E (i.e., α-tocopherol) supplementation use for the prevention of prostate cancer (CaP); however, associations of different tocopherol forms and CaP aggressiveness have yet to be examined.Methods
This study examined whether food intake of tocopherols, vitamin E supplement use, and adipose tissue biomarkers of tocopherol were associated with CaP aggressiveness among African-American (AA, n = 1,023) and European-American (EA, n = 1,079) men diagnosed with incident CaP. Dietary tocopherols were estimated from a food frequency questionnaire, supplement use from questionnaire/inventory, and biomarkers from abdominal adipose samples measured using high-performance liquid chromatography. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were estimated from logistic regression comparing high-aggressive CaP to low/intermediate aggressive CaP, adjusting for covariates.ResultsDietary intakes of α-and δ-tocopherol were related inversely to CaP aggressiveness among EAs [OR (95%CI), highest versus lowest quartile: α-tocopherol, 0.34 (0.17–0.69), Ptrend = 0.006; δ-tocopherol, 0.45 (0.21–0.95) Ptrend = 0.007]. Inverse associations between dietary and supplemental α-tocopherol and CaP aggressiveness were observed among AAs, though these did not reach statistical significance [OR (95%CI), highest versus lowest quartile: dietary α-tocopherol, 0.58 (0.28–1.19), Ptrend = 0.20; supplemental α-tocopherol, 0.64 (0.31–1.21) Ptrend = 0.15]. No significant association was observed between adipose tocopherol levels and CaP aggressiveness [OR (95%CI), highest versus lowest quartiles of α-tocopherol for EAs 1.43 (0.66–3.11) and AAs 0.66 (0.27–1.62)].Conclusions
The inverse associations observed between dietary sources of tocopherols and CaP aggressiveness suggests a beneficial role of food sources of these tocopherols in CaP aggressiveness. Prostate © 2015 Wiley Periodicals, Inc.
Information regarding post-diagnostic dairy intake and prostate cancer survival is limited. We evaluated intake of total, high-fat and low-fat dairy after prostate cancer diagnosis in relation to disease-specific and total mortality. We included 926 men from the Physicians' Health Study diagnosed with non-metastatic prostate cancer between 1982 and 2000 who completed a diet questionnaire a median of 5 years after diagnosis and were followed thereafter for a median of 10 years to assess mortality. Cox proportional hazards regression was used to estimate associations between dairy intake and prostate cancer specific and all-cause mortality. During 8,903 person-years of follow-up, 333 men died, 56 due to prostate cancer. Men consuming ≥3 servings/day of total dairy products had a 76% higher risk of total mortality and a 141% higher risk of prostate cancer-specific mortality compared to men who consumed less than 1 dairy product/day (relative risk (RR) = 1.76, 95% confidence interval (CI): 1.21, 2.55, Ptrend < 0.001 for total mortality; RR = 2.41, 95%CI: 0.96, 6.02, Ptrend = 0.04 for prostate cancer specific mortality). The association between high-fat dairy and mortality risk appeared to be stronger than that of low-fat dairy, but the difference between them was not statistically significant (P for difference = 0.57 for prostate cancer-specific mortality and 0.56 for total mortality). Among men without metastases when diagnosed, higher intake of dairy foods after prostate cancer diagnosis may be associated with increased prostate cancer-specific and all-cause mortality. This article is protected by copyright. All rights reserved.
© 2015 UICC.
Introduction:
We aimed to investigate the role of IGF-1 related pathway in high-fat diet (HFD) promotion of TRAMP mouse PCa progression.
Methods:
TRAMP mice were randomly divided into two groups: HFD group and normal diet group. TRAMP mice of both groups were sacrificed and sampled on the 20th, 24th and 28th week respectively. Serum levels of insulin, IGF-1 and IGF-2 were tested by ELISA. Prostate tissue of TRAMP mice was used for both HE staining and immunohistochemical staining of IGF-1 related pathway proteins, including IGF-1Rα, IGF -1Rβ, IGFBPs and AKT.
Results:
The mortality of TRAMP mice from HFD group was significantly higher than that of normal diet group (23.81% and 7.14%, p=.035). The tumor incidence of HFD TRAMP mice at 20(th) week was significantly higher than normal diet group (78.57% and 35.71%, p=.022). Serum IGF-1 level of HFD TRAMP mice was significantly higher than that of normal diet TRAMP mice. Serum IGF-1 level tended to increase with HFD TRAMP mice's age. HFD TRAMP mice had higher positive staining rate of IGF-1Rα, IGF-1Rβ, IGFBP3 and Akt than normal diet TRAMP mice.
Conclusions:
IGF-1 related pathway played an important role in high-fat diet promotion of TRAMP mouse PCa development and progression.
High calcium intake has been associated with an increased risk of advanced-stage and high-grade prostate cancer. Several studies have found a positive association between phosphorus intake and prostate cancer risk.
We investigated the joint association between calcium and phosphorus and risk of prostate cancer in the Health Professionals Follow-Up Study, with a focus on lethal and high-grade disease.
In total, 47,885 men in the cohort reported diet data in 1986 and every 4 y thereafter. From 1986 to 2010, 5861 cases of prostate cancer were identified, including 789 lethal cancers (fatal or metastatic). We used Cox proportional hazards models to assess the association between calcium and phosphorus intake and prostate cancer, with adjustment for potential confounding.
Calcium intakes >2000 mg/d were associated with greater risk of total prostate cancer and lethal and high-grade cancers. These associations were attenuated and no longer statistically significant when phosphorus intake was adjusted for. Phosphorus intake was associated with greater risk of total, lethal, and high-grade cancers, independent of calcium and intakes of red meat, white meat, dairy, and fish. In latency analysis, calcium and phosphorus had independent effects for different time periods between exposure and diagnosis. Calcium intake was associated with an increased risk of advanced-stage and high-grade disease 12-16 y after exposure, whereas high phosphorus was associated with increased risk of advanced-stage and high-grade disease 0-8 y after exposure.
Phosphorus is independently associated with risk of lethal and high-grade prostate cancer. Calcium may not have a strong independent effect on prostate cancer risk except with long latency periods.
© 2015 American Society for Nutrition.
Aims:
Despite recent advances in prostate cancer diagnostics and therapeutics, the overall survival rate still remains low. This study was aimed to assess potential anti-cancer activity of maysin, a major flavonoid of corn silk (CS, Zea mays L.), in androgen-independent human prostate cancer cells (PC-3).
Main methods:
Maysin was isolated from CS of Kwangpyeongok, a Korean hybrid corn, via methanol extraction and preparative C18 reverse phase column chromatography. Maysin cytotoxicity was determined by either monitoring cell viability in various cancer cell lines by MTT assay or morphological changes. Apoptotic cell death was assessed by annexin V-FITC/PI double staining, depolarization of mitochondrial membrane potential (MMP), expression levels of Bcl-2 and pro-caspase-3 and by terminal transferase mediated dUTP-fluorescein nick end labeling (TUNEL) staining. Underlying mechanism in maysin-induced apoptosis of PC-3 cells was explored by evaluating its effects on Akt and ERK pathway.
Key findings:
Maysin dose-dependently reduced the PC-3 cell viability, with an 87% reduction at 200 μg/ml. Maysin treatment significantly induced apoptotic cell death, DNA fragmentation, depolarization of MMP, and reduction in Bcl-2 and pro-caspase-3 expression levels. Maysin also significantly attenuated phosphorylation of Akt and ERK. A combined treatment with maysin and other known anti-cancer agents, including 5-FU, etoposide, cisplatin, or camptothecin, synergistically enhanced PC-3 cell death.
Significance:
These results suggested for the first time that maysin inhibits the PC-3 cancer cell growth via stimulation of mitochondria-dependent apoptotic cell death and may have a strong therapeutic potential for the treatment of either chemo-resistant or androgen-independent human prostate cancer.
Background:
Recent posttrial analysis of a completed randomized trial found an increased risk of prostate cancer among healthy men taking high-dose vitamin E supplements. Trials that examined the effect of vitamin C supplements on cancer risk are few.
Objective:
We examined whether vitamin E or vitamin C supplementation affects the risk of cancer events during posttrial follow-up of the Physicians' Health Study II.
Design:
Beginning in 1997, a total of 14,641 US male physicians aged ≥50 y were randomly assigned to receive 400 IU of vitamin E every other day, 500 mg of vitamin C daily, or their respective placebos. The vitamin E and vitamin C treatment ended in 2007, and observational follow-up continued through June 2011.
Results:
This study included an additional 356 cases of incident prostate cancer and 771 total cancers that developed during a mean (maximum) of 2.8 (3.8) y of posttrial observation. During an overall mean of 10.3 (13.8) y, there were a total of 1373 incident prostate cancers and 2669 total cancers documented. In comparison with placebo, vitamin E supplementation had no effect on the incidence of prostate cancer (HR: 0.99; 95% CI: 0.89, 1.10) or total cancers (HR: 1.02; 95% CI: 0.95, 1.10). There was also no effect of vitamin C supplementation on total cancers (HR: 1.02; 95% CI: 0.94, 1.10) or incident prostate cancer (HR: 1.03; 95% CI: 0.93, 1.15). Neither vitamin E nor vitamin C supplementation had effects on other site-specific cancers overall. Stratification by known cancer risk factors, history of cancer, other randomized treatment, and follow-up time showed no significant interactions.
Conclusion:
In this large-scale randomized trial in men, vitamin E and C supplementation had no immediate or long-term effects on the risk of total cancers, prostate cancer, or other site-specific cancers.
Although several studies have reported that the peritoneum does not contribute to the formation of a fascia between the urogenital organs and rectum, Denonvilliers' fascia (DF), a fascia between the mesorectum and prostate (or vagina) in adults, is believed to be a remnant of the peritoneum. Remnants of the peritoneum, however, were reportedly difficult to detect in other fusion fasciae of the abdominopelvic region in mid-term fetuses. To examine morphological changes of the pelvic cul-de-sac of the peritoneum, we examined 18 male and 6 female embryos and fetuses. A typical cul-de-sac was observed only at 7 weeks, whereas, at later stages, the peritoneal cavity did not extend inferiorly to the level of the prostatic colliculus or the corresponding structure in females. The cul-de-sac had completely disappeared in front of the rectum at 8 weeks and homogeneous and loose mesenchymal tissue was present in front of the rectum at the level of the colliculus at 12-16 weeks. We found no evidence that linearly arranged mesenchymal cells developed into a definite fascia. Therefore, the development of the DF in later stages of fetal development may result from the mechanical stress on the increased volumes of the mesorectum, seminal vesicle, prostate and vagina and/or enlarged rectum. Therefore, we considered the DF as a tension-induced structure rather than a fusion fascia. Fasciae around the viscera seemed to be classified into (1) a fusion fascia, (2) a migration fascia and (3) a tension-induced fascia although the second and third types are likely to be overlapped.
Vitamin E (α-tocopherol) plays a key role in the regulation of cell growth and differentiation and has been studied as a potential chemopreventive agent for prostate cancer. The association of serum vitamin E concentrations with cancer risk may be modified by genetic variations in vitamin E-related genes. We examined whether variants in vitamin E-related genes were associated with risk of prostate cancer in a nested case-control study using 483 prostate cancer cases and 542 matched controls of European ancestry from a large U.S. multicenter trial that had available measurements of serum vitamin E concentrations and genotyping of 3 genome-wide association study meta-analysis-identified single-nucleotide polymorphisms (SNPs) associated with circulating vitamin E. ORs and 95% CIs were calculated using unconditional logistic regression adjusted for age, family history of prostate cancer, and serum total cholesterol. Findings suggest lower prostate cancer risk for men whose genotypes reflect higher vitamin E (i.e., α-tocopherol) status. An SNP (rs964184) near budding-site selection protein 13 [BUD13 (yeast)], zinc finger protein 259 (ZNF259), and apolipoprotein A5 (APOA5) on 11q23.3 was significantly associated with prostate cancer risk (per-allele OR = 0.75; 95% CI: 0.58, 0.98; P-trend = 0.03). The association between rs964184 and prostate cancer risk was stronger among homozygous carriers of the minor allele (OR = 0.27; 95% CI: 0.09, 0.83). Another variant, rs11057830 in scavenger receptor class-B member 1 (SCARB1) on 12p24.31, approached statistical significance (OR = 0.32; 95% CI: 0.10, 1.01, P = 0.05; 2 minor allele copies). This study suggests that polymorphisms near BUD13/ZNF259/APOA5, involved in vitamin E transport and metabolism, may be associated with lower risk of prostate cancer. This trial was registered at clinicaltrials.gov as NCT00002540.
In the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study among 29,133 Finnish male smokers aged 50-69 years, daily α-tocopherol (50 mg) for a median of 6.1 years decreased the risk of prostate cancer, whereas β-carotene (20 mg) increased risk of lung cancer and overall mortality. To determine the postintervention effects of α-tocopherol and β-carotene, 25,563 men were followed 18 years for cancer incidence and all causes of mortality through national registers. Neither supplement had significant effects on post-trial cancer incidence. Relative risk (RR) for lung cancer (n = 2,881) was 1.04 (95% confidence interval [CI], 0.96-1.11) among β-carotene recipients compared with nonrecipients. For prostate cancer (n = 2,321), RR was 0.97 (95% CI, 0.89-1.05) among α-tocopherol recipients compared with nonrecipients with the preventive effect of α-tocopherol continuing ∼8 years postintervention. Body mass index significantly modified the effect of α-tocopherol on prostate cancer (p for interaction = 0.01) RR 1.00 (95% CI, 0.88-1.14) in normal-weight men, 0.87 (95% CI, 0.77-0.98) in overweight men, and 1.25 (95% CI, 1.01-1.55) in obese men. The post-trial relative mortality (based on 16,686 deaths) was 1.02 (95% CI, 0.98-1.05) for α-tocopherol recipients compared with nonrecipients and 1.02 (95% CI, 0.99-1.05) for β-carotene recipients compared with nonrecipients. α-Tocopherol decreased post-trial prostate cancer mortality (RR, 0.84; 95% CI, 0.70-0.99), whereas β-carotene increased it (RR, 1.20; 95% CI, 1.01-1.42). In conclusion, supplementation with α-tocopherol and β-carotene appeared to have no late effects on cancer incidence. The preventive effect of moderate-dose α-tocopherol on prostate cancer continued several years post-trial and resulted in lower prostate cancer mortality.