Bob Djavan

Chemopreventive effects of resveratrol and resveratrol derivatives

Resveratrol is considered to have a number of beneficial effects. Recently, our group modified the molecule and synthesized a number of compounds with different biochemical effects. Polymethoxy and polyhydroxy derivatives of resveratrol were shown to inhibit tumor cell growth in various cell lines and inflammation pathways (cyclooxygenases activity), in part more effectively than resveratrol itself. One lead compound (hexahydroxystilbene, M8) turned out to be the most effective inhibitor of tumor cell growth and of cyclooxygenase 2 activity. M8 was then studied in two different human melanoma mouse models. This novel resveratrol analog was able to inhibit melanoma tumors in a primary tumor model alone and in combination with dacarbacine, an anticancer compound that is used for melanoma treatment. We also tested the development of lymph node metastasis in a second melanoma model and again M8 successfully inhibited the tumor as well as the size and weight of lymph node metastasis. Hydroxylated resveratrol analogs therefore represent a novel class of anticancer compounds and promising candidates for in vivo studies.

Correlation between benign prostatic hyperplasia and inflammation.

Purpose of reviewThis review aims to evaluate the available evidence on the role of prostatic inflammation in the pathogenesis and progression of benign prostatic hyperplasia (BPH). Recent findingsAlthough there is still no evidence of a causal relation, accumulating evidence suggests that inflammation may contribute to the development of BPH and lower urinary tract symptoms (LUTS). Inflammatory infiltrates are frequently observed in prostate tissue specimens from men with BPH and the presence or degree of inflammation has been found to be correlated with prostate volume and weight. The inflammatory injury may contribute to cytokine production by inflammatory cells driving local growth factor production and angiogenesis in the prostatic tissue. This proinflammatory microenvironment is closely related to BPH stromal hyperproliferation and tissue remodeling with a local hypoxia induced by increased oxygen demands by proliferating cells which supports chronic inflammation as a source of oxidative stress leading to tissue injury in infiltrating area. SummaryAlthough the pathogenesis of BPH is not yet fully understood and several mechanisms seem to be involved in the development and progression, recent studies strongly suggest that BPH is an immune inflammatory disease. The T-cell activity and associated autoimmune reaction seem to induce epithelial and stromal cell proliferation. Further understanding of the role of inflammation in BPH and clinical detection of this inflammation will expand the understanding of BPH pathogenesis and its histologic and clinical progression, allow risk stratification for patients presenting with BPH-related LUTS, and suggest novel treatment strategies.

Gene polymorphisms and prostate cancer: the evidence.

Prostate cancer is still the most frequent noncutaneous male malignancy and is the second most common cause of cancer death. Genetic factors have been extensively studied in different countries. In addition, numerous genome–wide association studies have been performed in developed countries. Genetic tests will be applied in the near future for diagnosis, therapeutic, and prognostic significance. Therefore, we reviewed the association of several important pathways and genes with critical functions in prostate cancer development or progression.

Role of Testosterone in Managing Advanced Prostate Cancer

Androgen deprivation therapy is frequently used to treat patients with advanced prostate cancer. New therapies for metastatic castration-resistant prostate cancer have drawn increased attention to serum and intratumoral testosterone levels. The present review examines the role of testosterone in prostate cancer progression, discusses the nuances and potential pitfalls in measuring serum testosterone using available assays, and summarizes current data relevant to the arguments for and against achieving and maintaining the lowest possible testosterone levels during androgen deprivation therapy, including the adverse effects of such treatment. Incorporating this information, we have made recommendations incorporating testosterone evaluation and its effect on the clinical decision-making process.

Hormonal manipulation of benign prostatic hyperplasia.

Purpose of reviewWe provide new viewpoints of hormonal control of benign prostatic hyperplasia (BPH). The latest treatment findings with 5-alpha reductase inhibitors (5-ARIs) finasteride and dutasteride, refined indications, efficacy, and safety are discussed and compared. We also discuss potential new 5-ARIs and other hormonal treatments. Recent findingsFinasteride and dutasteride have equal efficacy and safety for the treatment and prevention of progression of BPH. 5-ARIs are especially recommended for prostates greater than 40 ml and PSA greater than 1.5 ng/ml. Combination therapy is the treatment of choice in these patients, but with prostate volume greater than 58 ml or International Prostate Symptom Score of at least 20, combinations have no advantage over 5-ARI monotherapy. Updates on the recent developments on BPH therapy with luteinizing hormone-releasing hormone (LHRH) antagonist are also reviewed and analyzed. Preclinical studies suggest that growth hormone-releasing hormone (GHRH) antagonists effectively shrink experimentally enlarged prostates alone or in combination with LHRH antagonists. SummaryNew 5-ARIs seem to be the promising agents that need further study. Preclinical studies revealed that GHRH and LHRH antagonists both can cause a reduction in prostate volume. Recent data indicate that prostate shrinkage is induced by the direct inhibitory action of GHRH and of LHRH antagonists exerted through prostatic receptors. The adverse effects of 5ARIs encourage alternative therapy.

Benign Prostatic Hyperplasia: Current Clinical Practice

Benign prostatic hyperplasia (BPH) is the most common benign adenoma in men, affecting nearly all of them. BPH represents a clinically significant cause of bladder outflow obstruction in up to 40% of men. The growing frequency of diagnosis is due to increasing life expectancy and a trend toward seeking medical advice at earlier stages of the disease. The last decade has witnessed a significant shift in emphasis in the management of BPH, with medical therapies and, to a lesser extent, minimally invasive therapies becoming the predominant active therapy choices. The development of effective therapies such as alpha-adrenergic blockers and 5-alpha-reductase inhibitors and the possibility of their combined use represent the most significant advance in the treatment of BPH.

Blood loss during radical prostatectomy: impact on clinical, oncological and functional outcomes and complication rates

Study Type – Outcomes (cohort)

Prostate-specific Antigen Testing and Prostate Cancer Screening

Prostate specific antigen (PSA) screening is an integral part of current screening for prostate cancer. Together with digital rectal examinations, it is recommended annually by the American Cancer Society. PSA screening has resulted in a significant stage migration in the past decades. Different forms of PSA, including free PSA, volume adjusted, complexed, intact, or pro-PSA, are being used in the screening process. Other aspects of the screening process include age at diagnosis, survival, overdiagnosis, and overtreatment. Recent studies have cast doubt on whether PSA screening positively affects mortality and how the quality of life of patients may be affected by screening. Future considerations include the need for more longitudinal studies as well as further study of the PSA components that may become more relevant in the future.

Testosterone in prostate cancer: the Bethesda consensus.

Whats known on the subject? and What does the study add?

Screening for Prostate Cancer: Practical Analysis of the ESRPC and PLCO Trials

Similar to other common malignancies such as breast and cervical cancers, the issue of population screening with prostate-specific antigen (PSA) appears enticing, and the American health care model provides us with some insight into this matter with its advocated policy of screening since the early 1990s. The current recommendation from the American Cancer Society is that both PSA testing and digital rectal examination (DRE) should be offered annually to men aged>50with a life expectancy of at least 10 yr. Populations with higher risk factors, such as African American men or thosewith a relativewith prostate cancer (PCa), should begin testing at age 45 [1]. Three recent studies—the 2001 Tyrol Study, the US-based Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, and the European Randomized Study of Screening for Prostate Cancer (ERSPC)—are being digested currently by the urology community [2–4] (Table 1). Published inMarch 2009, the ERSPC and PLCOstudies present the most comprehensive and up-to-date findings on PCa screening available today. Theyhave significantly contributed toourcurrentknowledgeandunderstandingofPCascreening, as well as the difficulties and controversies associated with their ambiguous findings. Two cases will help us understand the controversy and issues related to PCa screening today. Considering the hypothetical case of a 59-yr-old teacher, presenting to his urologist withmild urinary symptoms and asking for a checkup, and the case of a 75-yr-old retired bus driver with a positive family history, slight back pain, and a serum PSA of 2.3 ng/ml (performed 3 yr earlier) asking for a routine check as well, we could engage in a heated debate. Indeed both the European and the US trials are wanting in guiding the urologist in every individual case.