J. Curtis Nickel, MD, FRCSC

J. Curtis Nickel, MD, FRCSC

Queen's University

Kingston, Ontario, Canada

Dr. Nickel is the Canada Research Chair in Urologic Pain and Inflammation and a Professor of Urology at Queen’s University in Kingston, Ontario. He is also a staff urologist at Kingston General Hospital. Dr. Nickel’s research covers inflammatory, benign prostate, and pain diseases of the urinary tract. He has over 550 publications, is on the editorial board of eight urology journals, serves as editor of the AUA Update Series, has presented in 45 countries, and is funded by the US NIH and Canadian CIHR. He has been awarded a CIHR Tier I Canada Research Chair (until 2021), as well as an AUA Distinguished Contribution Award and SIU Academy Award. He is currently Immediate Past-President of the Canadian Urological Association.

Disclosures:

Talks by J. Curtis Nickel, MD, FRCSC

Saw Palmetto for BPH, Prostate Cancer, or Prostatitis?

J. Curtis Nickel, MD, FRCSC, the Canada Research Chair in Urologic Pain and Inflammation and Professor of Urology at Queen’s University in Kingston, Ontario, discusses research on the herbal medicine saw palmetto and its efficacy as an alternative therapy for benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS), prostatitis, and prostate cancer. He relates the history of saw palmetto, explaining that it has been used to treat urinary problems for centuries, but fell out of widespread use in North America at the start of the the modern pharmaceutical era in the 1920s, though physicians in Europe continued prescribing it. Dr. Nickel notes that there are two primary forms of saw palmetto products in North America: saw palmetto extract, which is high in fatty acids; and saw palmetto ground berry powder, which is low in fatty acids. Dr. Nickel emphasizes that the presence of fatty acids is important since prostate cells preferentially take up fatty acids and sterols. He highlights the difference between the North American guidelines, which state that “the available data do not suggest that saw palmetto has a clinically meaningful effect on LUTS secondary to BPH,” and the European guidelines which recommend using saw palmetto on the “basis of its long-standing use.” Dr. Nickel then considers the evidence, explaining that a literature review of 1575 research publications on saw palmetto and LUTS indicates saw palmetto extracts are safe, improve symptoms, and improve quality of life. He then looks at the potential role of saw palmetto in treating prostatitis, a prevalent condition in North American men. Dr. Nickel explains that until recently, researchers could not find evidence from randomized placebo-controlled trials to substantiate findings that the hexanic extract of saw palmetto reduces prostate inflammation. However, he notes, a recent trial suggests saw palmetto extract is effective, safe, and clinically superior to placebo for the treatment of chronic prostatitis/chronic pelvic pain syndrome. Dr. Nickel then turns to the question of whether or not saw palmetto could have a role in managing prostate cancer. He explains that saw palmetto seems like it could have value in preventing or managing prostate cancer since it antagonizes 5ɑ-reductase to reduce DHT production, inhibits DHT binding to androgen receptors, inhibits the expression of Cox-2, inhibits prostate cell growth, etc. However, studies have not found any association between use of saw palmetto and risk of prostate cancer development, nor any correlation with increasing frequency or duration of use. Dr. Nickel concludes that saw palmetto extract is a valuable alternative therapy for men with mild to moderate LUTS/BPH, that it is potentially a useful alternative therapy for prostatitis, and that it does not play a role in prostate cancer prevention or treatment in 2022.

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Saw Palmetto and BPH – Past, Present, and Future

After an introduction from E. David Crawford, MD, Professor of Urology at the University of California, San Diego, and Editor-in Chief of Grand Rounds in Urology, Mark A. Moyad, MD, MPH, the Jenkins/Pokempner Director of Preventive/Complementary and Alternative Medicine (CAM) at the University of Michigan Medical Center in the Department of Urology in Ann Arbor, Michigan, interviews J. Curtis Nickel, MD, FRCSC, the Canada Research Chair in Urologic Pain and Inflammation and Professor of Urology at Queen’s University in Kingston, Ontario, on the history of the herbal medicine saw palmetto and its efficacy as alternative medicine for benign prostatic hyperplasia (BPH). Dr. Moyad observes that in the early 2000s, saw palmetto was widely discussed in North America, but seems to have disappeared from the conversation in recent years. Dr. Nickel explains that while this is true, saw palmetto continues to be developed as a treatment option in Europe. He then notes that the STEP and CAMUS trials were some of the main contributors to North American loss of interest. The 2006 STEP trial failed to prove that saw palmetto had greater efficacy than placebo in BPH by North American medical standards, which Dr. Nickel believes was due to there being different forms and sources of saw palmetto extract and it being difficult to control for which would be used in a study at the time in North America. Dr. Moyad highlights that while this trial may not have found a benefit to saw palmetto, it also found it to be as safe as placebo. Dr. Nickel then goes into further detail about the CAMUS trial, which he worked on, and which was initially based heavily on European studies. However, due to the negative results of the STEP trial, CAMUS was redesigned, and ultimately it too found little difference between saw palmetto and placebo. Dr. Nickel notes that he feels that he and his fellow researchers may have missed something critical in that trial, and ponders why the two North American studies had negative results while so many other trials had positive ones. He also notes that he continues to recommend saw palmetto as an adjunct therapy to many of his patients based on the international literature. Drs. Moyad and Nickel then discuss some of the sourcing difficulties related to saw palmetto, as well as different extraction methods. Dr. Moyad then references Permixon, a European medicinal product derived from saw palmetto, and Dr. Nickel discusses how the way that it is regulated and processed differs from how saw palmetto is handled in North America. Dr. Nickel clarifies that he thinks that saw palmetto is a good alternative treatment for BPH patients looking for less invasive disease management options as long as a USP (US Pharmacopeial Convention)-approved product that is analyzed thoroughly is used.

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Beyond Antibiotics: Introducing Vaccine-Based Approaches to Recurrent UTIs in Women

J. Curtis Nickel, MD, FRCSC, the Canada Research Chair in Urologic Pain and Inflammation and Professor of Urology at Queen’s University in Kingston, Ontario, gives an overview of current and prospective treatment for recurrent urinary tract infections (UTIs), focusing on alternatives to antibiotics. He begins by summarizing the history of antibiotics for UTIs, noting that new antibiotics were discovered very quickly from the 1940s through the 1970s and that doctors believed at the time that infectious diseases would soon be a problem of the past. However, antibiotic-resistant microbes are now so prevalent that Dr. Nickel suggests that humanity is entering the “post-antibiotic era.” He then considers the available non-antibiotic treatments for recurrent UTI prevention in pre- and postmenopausal women. For premenopausal women, traditionally-recommended alternative prophylactic treatments include changes in hygiene practices, pre- and post-coital voiding, and avoidance of hot tubs, tampon use, and douching, but guidelines say that case-control studies demonstrate that these suggestions do not significantly impact recurrent UTI risk and can reinforce shame and self-blame. Dr. Nickel lists several alternative therapies with varying levels of evidence for this cohort, including increased water intake, cranberry extract, probiotics such as D-mannose, and methenamine hippurate. Dr. Nickel also recommends probiotics, D-mannose, and cranberry for postmenopausal women, though he also notes that the evidence-based approach for this cohort is vaginal estrogen therapy. According to Dr. Nickel, the future of recurrent UTI prevention for both cohorts is a vaccine. In the final part of his presentation, Dr. Nickel looks at treatment options for symptomatic UTI. Guidelines suggest antibiotics in these cases, but evidence indicates that UTI is typically self-limited and rarely progresses to more severe disease, and that there is little benefit to antibiotics for UTI beyond modestly faster symptomatic improvement. Dr. Nickel suggests treating symptomatic UTI with phenazopyridine, NSAIDS, urine alkalization, methenamine hippurate, and even herbal and dietary therapies. After summarizing his key points, Dr. Klotz goes into greater depth regarding vaccines for UTI prevention in a conversation with E. David Crawford, MD.

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An Introduction to the Urinary Microbiome: Part 3 – Manipulating the Microbiome for Urologic Health

In the third lecture of a three-part foundational series for Grand Rounds in Urology’s Next Generation Microbiome and Urologic Infections Learning Center, J. Curtis Nickel, MD, FRCSC, Professor of Urology at Queen’s University in Ontario, Canada, discusses possible ways to manipulate the microbiome to promote urologic health. He explains that, at present, there are four basic ways to positively influence the microbiome: eating a good diet, exercising, avoiding environmental pollution, and avoiding unnecessary antibiotics. Dr. Nickel also discusses various potential treatments currently being explored that involve manipulating the microbiome for managing disease, such as: gastrointestinal recolonization with Oxalobacter formigenes to treat urinary stone disease; targeting particular microbiota for cancer management; using Lactobacillus probiotics, fecal transplants, urine transplants, and a whole-cell inactivated bacteria vaccine to protect against urinary tract infections; and phage therapy. Dr. Nickel concludes that urologists do not have to always kill off bacteria, including seemingly pathogenic bacteria, but rather they need to understand how the bacteria changes in various disease states.

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An Introduction to the Urinary Microbiome: Part 2 – Impact on Urinary Disease

In the second lecture of a three-part foundational series for Grand Rounds in Urology’s Next Generation Microbiome and Urologic Infections Learning Center, J. Curtis Nickel, MD, FRCSC, Professor of Urology at Queen’s University in Ontario, Canada, discusses how changes to the urinary microbiome, which he previously described as helping maintain urinary health, can contribute to the development of urinary disease. Dr. Nickel summarizes the findings of several studies that evaluate the impact of the microbiome on urologic chronic pelvic pain, observing that dysbiosis appears to be more important than any particular bacterium in the development of chronic prostatitis/chronic pelvic pain syndrome, female bladder pain, and female lower urinary tract symptoms (LUTS), although researchers have identified some candidate organisms. Dr. Nickel notes that the development of struvite stones and calcium oxalate stones are also associated with dysbiosis. He concludes by discussing the role of bacteria in urinary cancers, explaining that distinct microbiome patterns appear to be related to certain responses to bladder cancer, and that prostate cancer is often associated with prostate inflammation caused by bacterial infection, although the role of the microbiome in prostate cancer development has yet to be determined.

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