Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

How I Survive Cancer

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Erin Maloney, Intrepid explorer, Amateur photographer, Aspiring leader; Toronto, ON;
Email: erinLmaloney@gmail.com

Q: You have recently disclosed that you have had a diagnosis of cancer and described your experience in some detail on Medium. What does it mean to you to be a “Cancer Survivor”?

A: Calling myself a survivor sometimes feels like an exaggeration. In 2016, I was diagnosed with Stage 1A2 squamous cell carcinoma of the cervix. It began with a routine pap smear and led to a robotic laparoscopic radical trachelectomy seven months later. Every procedure was challenging, and surgery was particularly arduous. However, I did not have to endure radiation, brachytherapy, or chemotherapy. I got to keep my hair, didn’t have to cope with nausea or worry about the lifelong maintenance required after radiation. So, in many ways, calling myself a survivor feels fraudulent. I have it too easy.
The physical recovery was relatively smooth but there is no preparation available for the mental toll of the Big C diagnosis. After the gynecologist shared the news, everything moved quickly. Within 10 days I had an MRI and was in consultation at Princess Margaret Cancer Hospital. It did not leave much room for preparation. In a very brief timeframe, I went from being a healthy 32-year old with no plans to have children to being a 33-year old who might not have a say in the matter.
People expect others to react in a binary way to that kind of news. There is a belief that one can choose to be optimistic or pessimistic, but that is a false dichotomy. Some days optimism abounds; most days, the fear brews below the surface unacknowledged. I mentally created a list of unanswerable questions (Would a hysterectomy be better? Would I feel like less of a woman? What if it comes back? How do I cope with this forever? Is this what kills me?). I researched and armed myself with information – a coping mechanism that allowed me to ignore my own terror.
I am not the same person I was a year ago. Prior to this, I was entrenched in the pitfalls of my Type A personality: a planner and organizer, domineering and determined, opinionated and unwilling to compromise. I had big ambitions and undaunted confidence. But our best-laid plans can be laid waste by a simple two-word sentence: “It’s cancer.” I wished I believed that this was part of some larger plan but it wasn’t. Instead, what it meant for me was that I had to change. My attitude needed to be different if I was going to come out the other side not completely broken.
Cancer took away my control. I could think of little else. Administrative inefficiencies rendered me powerless. I couldn’t get the answers I was seeking faster than they were willing to give them. For example, making decisions for myself was challenging when I needed answers from a busy surgeon. If I tried to use the same approach as I normally would, I would probably have ended up insane. So, I made the decision to adapt. I had to learn patience, to be more open to spontaneity, flexibility, and work on being able to ‘go with the flow.’ I try to allow humour and positivity to flow into impossible situations. I practice kindness and thoughtfulness as often as I can. I strive to think of others and notice their needs. Above all else, I try to treat people the way I want to be treated; to be more open and to deliver honesty without being cruel or callous.
There are many days when I fail at most of those things. Self-improvement is never easy. Imposed self-improvement as a survival mechanism is even more difficult. Finding and maintaining true positivity in the face of overwhelming terror has been the hardest task of all.
The depression that surfaced during recovery was different; it was borne out of a deep desire to live and the constant fear that I might not. I still don’t have certainty. The fear that surrounds each appointment will never abate. In a strange way, that has been inspiring. I want to live. I want a full, vibrant life that is technicolour. It doesn’t mean every day, and it doesn’t mean I get to tick off all those dreams immediately. Ultimately it means that I want to live better and that’s what makes me a survivor.
Erin Maloney’s contact info is included in the author affiliations at the top of this page.
Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

Who Owns Patient Data in Clinical Research?

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Charlotte J. Haug, MD, PhD, MSc, International Correspondent, New England Journal of Medicine; Senior Scientist, SINTEF Techology and Society; Adjunct Affiliate, Stanford Health Policy; Oslo, Norway;
Email: charlottejohanne@gmail.com

Q: Many people are coming to believe that active patient participation will be a key to more rapid movement forward in cancer research. Data sharing can help. But who owns the data? And what rights and responsibilities are thus conferred? Your recent NEJM article provides helpful background. Can you help us better understand?

A: Exchange of data between patients and doctors is essential for the practice of medicine – and patient data are essential for medical research and progress.
Traditionally, doctors collected patients’ health information (typically the medical history, laboratory tests, drugs prescribed, outcome of treatment, etc.) and sometimes shared that information, in confidence, with colleagues to seek advice and advance science. The medical record was the physician’s property, and still is in many countries and legislations. But do physicians own the patient data?
In clinical research, patient data from many sources must be collected and analyzed. Researchers must have explicit and informed consent from participating patients to do this, but when they have such consent they are free to use the trial data any way they wish. This is true even for commercial purposes – the norm for drug trials. But do researchers own the patient data?
Until quite recently the question of who owns patient data collected in clinical practice and clinical trials has not been discussed very much, mostly because it hasn’t been very important. Medical records and research results were analyzed and archived on paper. It was difficult, if not impossible, to reuse those data for anything else. Claiming ownership had no real value.
Internet, digitalization of medical records and datasets, and the vast increase in data-storage and data-processing power (especially over the last decade) has changed that. Since it is now possible to combine and reanalyze huge datasets quickly in totally new ways to create useful information about diseases and treatments, it is important to clarify who owns the data in order to clarify who can give permission to share and use data in ways beyond the original intent.
So far, the discussion about data sharing and data ownership has largely taken place between clinical trialists (who spend years collecting, curating, and analyzing data from clinical trials) and data scientists (who would like to add value to those data by reanalyzing and reusing them in novel ways). Both sides claim to have the patient’s and the public’s best interests at heart. But not many have asked patients what those interests are.
At a NEJM conference earlier this year, patients were asked this question. It turns out most of them want to share their data and to share them quickly, especially to ensure that other patients know about possible side effects. But they also want some control over how the data are shared. For example, they would be more hesitant to participate if commercial or other interests were involved. Which is unfortunately the case in most clinical trials. Something many of the patients didn’t seem to be aware of.
But the new “digital patients” also don’t want to be passive observers and sources of research data. They want to use the power of the Internet to engage in their own care, interact with clinicians and fellow patients, create new knowledge, and suggest new ways of delivering health care. They believe in sharing data and experiences to help themselves and fellow patients.
Patients want their data used responsibly and to take part in generating and curating the data. So perhaps the question needs to be rephrased: Who should control how data are distributed and used by others? The patients themselves? Doctors and researchers? Research institutions or governments?
Laws vary from country to country. In the United States, for example, absent specific language to the contrary in informed consent documents, research participants don’t have to give specific permission for their deidentified data to be used by other researchers. Europe is moving in the opposite direction — requiring explicit consent for reuse of data or data sharing and allowing patients to withdraw their consent at any time.
Perhaps the solution to the data-sharing and privacy struggle lies in shifting data ownership and control to individual patients everywhere.
Charlotte Haug’s contact info is included in the author affiliations at the top of this page.
Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

Nicotine Addiction: Harm Reduction by E-cigarettes and Snus

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Joel L. Nitzkin, MD, Public Health Physician, New Orleans, LA
Email: jlnitzkin@gmail.com

Q: Tobacco smoking remains the most preventable primary form of cancer causation in Americans. A recent Medscape column urged that harm reduction for confirmed nicotine addicts is the kindest and most effective strategy. How can products like “snus” be helpful?

A: As noted by Dr. Michael Russell in 1976, people smoke for the nicotine, but die from the tar. According to CDC, about half of long-term smokers will die of a smoking-related disease. They estimate that about 480,000 Americans die from cigarette smoking each year, including about 50,000 from the environmental tobacco smoke. According to our best current estimates, snus and the other smokeless products used by American men pose little or no risk of cancer of the mouth or any other cancer. E-cigarettes, having no combustion and no tobacco, are likely similarly low in risk.
Snus, e-cigarettes, and other smokeless nicotine delivery products offer an interesting and unusual approach to reducing the deadly toll of addition to cigarette smoke. Rather than present themselves as drugs to treat a deadly disease, these products offer recreational substitutes for cigarettes that already enable large numbers of smokers to satisfy their urge to smoke while reducing the risk of potentially fatal cigarette-related cancer and other diseases by more than 95% (likely more than 99%). This is a public health benefit that can be secured for many more smokers, (at no cost to the taxpayer) by simply advising them of this difference in risk. Sweden, where most men use snus rather than cigarettes to satisfy their urge for nicotine, has the lowest rate of lung cancer among men in the Western world. There is even one small study that shows that e-cigarettes can get smokers not interested in quitting to quit by switching to this much lower risk product. All it takes is informing them of this difference in risk.
American public health authorities recognize that snus and e-cigarettes are much lower in risk than cigarettes. Their objection to allowing manufacturers to claim lower risk, however, is based on a very different concern. They object on the basis that advertising these products as lower in risk might attract teens and other non-smokers to tobacco-related products; and from there to cigarettes. Research published this last decade provides substantial evidence that such advertising would not be likely to attract teens to these lower-risk products who otherwise would not have taken up smoking.
For many years, the goal of public anti-smoking programming has been “a tobacco-free society.”This goal has been based on the premise that all non-pharmaceutical nicotine products are so addictive and so hazardous that none should be tolerated. This goal has also been interpreted as ruling out any consideration of any non-pharmaceutical nicotine product in any public health initiative. Now that we know that we can communicate reduced risk without attracting teens who otherwise would not have taken up smoking, the time has come to use this knowledge to further reduce the burden of addiction, illness, and death that cigarettes have imposed both in the USA and worldwide.
Joel Nitzkin’s contact info is included in the author affiliations at the top of this page.
Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

Pharmacogenomics for Clinical Use of Cannabis

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Saeed K. Alzghari, M.S., M.B.A. (HOM), Pharm.D., BCPS, Director of Clinical Pharmacy, Gulfstream Genomics, LLC., Dallas, TX;
Email: salzghari@gulfdiagnostics.com

Q: Proper use of Pharmacogenomics can inform better patient care in many potential ways. Pain relief by use of Cannabis instead of opioids shows substantial promise. How do you think pharmacogenomic study could guide intelligent clinical use of Cannabis?

A: Over the past decade, pharmacogenomics (the study of how genes affects a person’s response to drugs) has gained much ground. More than 160 drugs currently have pharmacogenomic labeling by the Food & Drug Administration (FDA) and the list is growing. The excitement that surrounds pharmacogenomics and the applications associated with this technology are endless.
In order to understand the role of cannabis for pain pharmacogenomics, one must understand how pain is treated. In my experience as an oncology pharmacist, I have seen first-hand the unbelievable amounts of opioids a cancer patient may take just to gain some relief. Pain is treated according to the World Health Organization’s (WHO) Pain Relief Ladder where pain is treated in steps based on severity (Figure 1). Steps 2 and 3 of the pain ladder begin to include opioids as part of the treatment course since, when used properly, opioids offer the best chance at reducing pain.

An important consideration that is often forgotten is the use of adjuvant agents to help reduce the amount of opioids used when treating pain in general or to help with different types of pain such as neuropathic pain. In regards to cancer, the first clinical trial to show that an adjuvant therapy can help with chemotherapy-induced peripheral neuropathy was duloxetine, a serotonin-norepinephrine reuptake inhibitor (SNRI), typically indicated for depression.
The role of cannabis in pain management, in my opinion, will most likely be as an adjuvant. I do not see cannabis completely eliminating the need for opioids in patients with moderate-to-severe pain, but I believe cannabis can reduce the amount of opioids a patient may take. The main pharmacogenomic focus for cannabis is related to two primary cannabinoid receptors (CB1-R and CBR-2) that marijuana acts upon. Cannabinoid receptors are of great interest to researchers since our own body produces endocannabinoids that play a role in pain. Research associated with genetic polymorphisms in the cannabinoid receptor CNR1 and CNR2 genes are in preliminary stages; however, these genes hold promise to optimize and individualize therapies that act on the cannabinoid receptor. Other pharmacogenetic markers and their role in patients taking cannabis are also being investigated.
The largest barrier to research related to cannabis is that marijuana is classified as a Schedule I controlled substance by the U.S. Drug Enforcement Administration. Researchers are restricted on how marijuana is studied and is a deterrent to those wanting to perform trials in U.S.-respected organizations, such as the American Cancer Society, that have taken the position in supporting the need for more scientific research associated with cannabis to provide better patient care. If marijuana is rescheduled in the U.S., then its barriers to research will be lifted and more studies involving the pharmacogenomics of cannabis can be performed to improve patient care.
Saeed Alzghari’s contact info is included in the author affiliations at the top of this page.
Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

Public Health Personalized Medicine

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Gualberto Ruaño, MD, PhD, President, Genomas Inc.; Medical Director, Laboratory of Personalized Health; Hartford, CT;
Email: g.ruano@genomas.net

Q: Public participation by contributing specimens to assess personal genomic information is rapidly increasing. How might this expansion of testing become actually useful for the health of the public?

A: The fields of public health and medicine share a common objective of maintaining the well- being of people, but with very different modes of operation. Medicine has historically focused on interventions to treat illness and restore health, while public health seeks to prevent disease. Hence, medicine generally focuses on the needs of the individual, while public health focuses on the population. Because of this division, policies that serve the common good are limited by the individuals who do not realize the intended benefit. Could prevention become personalized with genomic information so that public health is synonymous with personal health?
The two perspectives can be illustrated by the approaches for dealing with nutrition. Various food pyramids purporting to guide the amount of milk products, fruits and vegetables, grains and legumes, meat, and water have been proposed amid controversy. A school system that adopts a public health approach to the problem might implement a food pyramid based menu, thus increasing its compliance but at the risk of variable responses among its students. Some individuals may have a gene or a lifestyle that makes them benefit from one kind of nutrient while others may have undesired weight gain. If it were possible to identify those individuals who would benefit most from a particular nutrient, then it may be possible to optimize the program as a whole, by avoiding side effects and increasing efficiency. In effect, this effort would bring together aspects of the medical and the public health perspectives by personalizing the public health strategies, thus providing a method by which individuals can optimize their own health, and in the process, benefit the population at large.
I believe the current consumer genomic products offer a path to personal health. Many citizens are purchasing these services and depositing their genomes with companies that will offer various interpretations of the genomic data, as the consumer requires. So far, the leading interest has been ancestry, but business models are evolving to offer consumers a variety of windows on their genome to guide diet and exercise and even expose disease susceptibility (information that can be “opened” by purchasing different products and applications). The genome is sequenced or genotyped once, the information is stored and queried repeatedly depending on the need or interest.
In this scenario, most of the algorithms leading to an interpretation will not be results of causative inference. Knowledge that a particular genetic polymorphism will produce a given effect on the outcome is really limited to genetic diseases, some pharmacokinetic polymorphisms and various cancers. A practical standard would be to determine whether ensembles of particular polymorphisms are associated with the outcome, a relationship that most likely is not causative.
We must be alert to this developing model. This is not science, which has the ultimate goal of understanding mechanisms of pathophysiology. This is modeling for predicting outcomes based on associations that exist between individual genomic characteristics and the outcome of interest. This would allow us to improve our prediction of the response by incorporating information that is related to the outcome, but when we cannot be certain that the associations are causal, we must maintain a level of caution in using the predictions.
There are various technical and medical problems with this model. The first is the quality of the genomic data. In the laboratory profession we strive to maintain a given level of quality and reproducibility so the test results are clinical grade and support medical interventions. But in the genome storage model, there is likely none because the algorithms are sampling multiple polymorphisms, and some redundant ones because of linkage disequilibrium may become the actual quality control. The second limitation is the relative contribution of phenotypic characteristics versus genetic markers to a prediction. It may be that for some predictions, the bulk of the prediction is carried by the phenotype, and the genotype is a small percentage of the predictive power. But will this matter to the consumer?
I believe the genie is out of the bottle concerning consumer genomics, and that an antagonistic view of the field by the medical profession is not in the best interest of the consumer or our profession. In the evolving genome storage model, a number of vendors could provide the initial sampling of the personal genome, and yet other vendors could support a marketplace of algorithms to interpret the genome and provide guidance. Competing algorithms will probably exist so that the consumer can select or compare for the same prediction. The models become fluid and there will be various versions released to the market, each claiming to be more precise. If a vendor persuades the consumer to give feedback information on individual response, the models could become self-improving. I predict that this world of genome data obtained once coupled to a diversity of algorithms for querying will allow public health to become personalized. I further suspect that the interest in ancestry will propel much demand for algorithms related to longevity, wellness, nutrition and fitness. These are indeed the historically desired outcomes of sound public health policy, but enabled by the interpretations of the personal genome of each individual.

RELATED BLOGS AND COMMENTARIES OF INTEREST

Gualberto Ruaño’s contact info is included in the author affiliations at the top of this page.
Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

CDG at TLI

Psychiatric Drug Use by Medical Students and Residents

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Pamela Wible, MD, Founder of the Ideal Medical Care movement; Author of Physician Suicide Letters—Answered; Family medicine practitioner in Oregon;

Q: Medical students and residents are among the most important human resources in the United States. Yet we lose many during training due to suicide. Have you information you can share with our readers about the mental health and psychiatric drug use of medical students?

A: I asked 220 doctors: “Have you ever been depressed as a physician?” Ninety percent stated yes. Yet few seek professional help. Here’s what depressed doctors do (when nobody’s looking). Some drink alcohol, exercise obsessively, even steal psychiatric meds. Still more shocking—I discovered that 75% of med students (and new doctors) are now on psychiatric medications.
“I was told by the psychologist at my med school’s campus assistance program, that 75% of the class of 175 people were on antidepressants,” shares psychiatrist Dr. Jaya V. Nair. “He wasn’t joking. How broken is the system, that doctors have to be pushed into illness in order to be trained to do their job?”
How many docs do we lose per year to suicide? The equivalent of one medical school full of students wiped out annually. In my 2016 TEDMED talk, I explain why doctors kill themselves. Personally, I lost both doctors I dated in med school to suicide and 8 physicians in my small town. In 2012 I decided to run a suicide hotline for doctors. I’ve heard from so many suicidal doctors that I published a book of their suicide letters.
In 1990, even I was severely depressed as a first-year med student. So my mom (a psychiatrist) mailed me a bottle of Trazodone. I thought I was the only one. Turns out occupationally-induced depression is rampant in medical training. Now schools dole out antidepressants like candy. Stimulants are used by med students like steroids in athletes. So where do we go from here? Should med schools distribute samples of Zoloft and Adderall during orientation?
The problem is physicians must answer mental health questions (right next to questions on felonies and DUIs) to secure a medical license, hospital privileges, and participate with insurance plans. Check the YES box and be forced to disclose your “confidential” medical history and defend yourself—again and again–for your entire career. You get treated like a criminal for taking meds to cope with the torment of medical training (and practice).
Maybe that’s why so many future (and current) physicians sneak drugs and go off-the-grid for mental health care.
“I’ve been in practice 20 years and have been on antidepressants and anxiolytics for all of that time,” says Jason. “I drive 300 miles to seek care and always pay in cash. I am forced to lie on my state relicensing every year. There is no way in hell I would ever disclose this to the medical board—they are not our friends.”
What if we stop the mental health witch hunt on our doctors? Why not replace threats and punishment with safe confidential care? What if we address the root of the problem—the great sickness in medical education—rather than shifting blame to 75% of medical students for not having enough serotonin or dopamine or norepinephrine in their brains?
As scientists, we can’t continue to approach medical education reform as a neurotransmitter deficiency in medical students. Can we?

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Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

The Worst Phony Cancer Cures

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Stephen Barrett, MD, Retired Psychiatrist; Medical Editor for Quackwatch.org and 24 other consumer-protection Web sites; Publisher for Consumer Health Digest; Chapel Hill, NC;
Email: sbinfo@quackwatch.org

Q: Who tops your list as the most brazen promoters of phony cancer cures in the past 25 years?

A: Three people come to mind: Gregory Caplinger, Hulda Clark, and Dr. Lorraine Day.
Gregory Earl Caplinger died in 2009 while serving a 12-year prison sentence for fraud. For many years he claimed to be a distinguished and widely published medical doctor, professor, and researcher. However, he did not have a bona fide medical degree and accumulated more questionable “credentials” than any other impostor I have ever investigated or heard of. His bio listed more than 75 of them. A habitual con man, he got into legal trouble at least six times for defrauding people. During the mid-1990s, he began operating a clinic in the Dominican Republic that offered treatment to desperate cancer patients. In 2000, after a six-day trial, a North Carolina jury convicted him of wire fraud and money laundering related to “investments” in his phony remedy “ImmuStim.” In 2001, he was sentenced to federal prison and ordered to pay more than $1 million restitution to several victims.
Hulda Regehr Clark (1928-2009) falsely claimed to cure cancer, AIDS, and many other serious diseases with herbs and low-voltage electrical devices. She earned an accredited Ph.D. in zoology but practiced “naturopathy” based on a correspondence course obtained from a non-accredited correspondence school. She was best known for her book, Cure for All Cancers, which claimed that all cancers and many other diseases are caused by “parasites, toxins, and pollutants” and can be cured by killing the parasites and ridding the body of environmental chemicals. Clark used and promoted two medically worthless galvanometric devices. Her “Synchometer” allegedly identified diseased organs and detected toxic substances by noting whether the device made various sounds when “test substances” were placed on a plate. Her “Zapper” allegedly killed microorganisms with electrical energy without harming human tissue. Its use was based on the notion that all living things broadcast characteristic radio frequencies and that the device would issue counter-frequencies that killed unwanted organisms. Clark said she could tell when cancer and AIDS patients were cured within days or even a few hours after her treatment was begun. She died of complications of multiple myeloma under circumstances which suggest that her life was shortened by failure to seek timely medical care.
Lorraine Jeanette Day, M.D. (1937- ), would like people to believe that personal experiences have enabled her to discover the answer to cancer. Unlike Caplinger and Clark, Day has excellent credentials (as an orthopedic surgeon), but in 1989, she suddenly withdrew from medical practice. A few years later, she underwent diagnostic and incisional biopsies for breast cancer. About 20 years ago, she began marketing educational videotapes which claim that her cancer ultimately caused her to become deathly ill and bedridden for many months, but cured herself with a combination of diet and prayer. However, portions of medical records suggest that she had an early-stage intraductal carcinoma that was completely removed during her second biopsy. (She could easily address this issue but has refused repeated requests for the relevant medical records.) Day advises people not to trust the medical profession and claims that standard cancer treatment has never cured anyone. Instead, she recommends strengthening the immune system by dietary means and other methods recommended in her educational materials. Day’s medical credentials and apparent sincerity make her particularly dangerous. A few people have told me about relatives with treatable cancers who shortened their life by relying on Day’s advice instead of standard care.

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Stephen Barrett’s contact info is included in the author affiliations at the top of this page.
Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

Nordic Country Tobacco Control

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Astrid Nylenna, MD, Acting Head of Department, Department of Global Health, Norwegian Directorate of Health, Oslo, Norway;
Email: Astrid.Nylenna@helsedir.no

Q: Norway has been very active in tobacco control and prevention with some success. To what do you attribute the success Norway has had and are there any lessons from other Scandinavian countries that might be useful, potential approaches for other developed countries?

A: The success in the reduction of cigarette smoking is hard to assign to one single act of regulation or a specific campaign because it is the combination of many simultaneous efforts over the years. The prevalence of daily smoking in Norway declined by more than half in the past 10 years and has reached 12% in 2016 for people 16-74 years old. For young people between 16-24 years of age, the reduction has been even steeper and only 3% were daily smokers in 2016. The mean age of daily smokers has increased, showing that the main reason for the reduction in daily smoking is a decline in recruitment. The use of smokeless tobacco, snus, has risen in the past decade, especially among young people.
The Norwegian tobacco control policy includes a national tobacco control strategy, high taxes, a ban on advertising, age limits (18 years), comprehensive smoking bans, ban on the display of tobacco products, pictorial warnings, ban of packs < 20, normative provision on children’s rights to a smoke-free environment, and tobacco-free schools. Tobacco advertising was banned already in 1973. Norway was the first country in the world to ratify the WHO Framework Convention on Tobacco Control (FCTC) in 2003. In July 2017 Norway introduced plain packaging and became the first country in the world to introduce standardized snus boxes without logo and colors. (For more information: Helsedirektoratet, Folkehelseinstituttet (FHI, which translates to Norwegian Institute of Public Health), Tobacco Control Laws – Norway Summary)
Mass media campaigning is a key element in the present tobacco control strategy. Campaigns are informed by research literature, trends in tobacco use prevalence, dialogue with tobacco users, and trends in media use (especially social media). The decline in recruitment among young people indicates the need for emphasis on smoking cessation. The majority of daily smokers have a desire to quit, demonstrating a huge potential for helping people to quit smoking by promoting cessation tools and assistance. In the past five years, there have been mass media campaigns on a regular basis–including social media–offering cessation information.
One of the cessation tools being promoted is the free smart phone app “Slutta” (“Quit”) developed by the Norwegian Directorate of Health. It has been a huge success, downloaded 550,000 times since its launch in 2013. In a country of 5.5 million inhabitants and about 1 million tobacco users (both daily and occasional use of cigarettes and snus/snuff) the number of downloads is quite remarkable.
The Nordic countries collaborate and discuss tobacco issues. All the Nordic countries have strict tobacco laws and have seen a decline in daily smoking. One example is Finland, which has set a goal of becoming smoke free by 2040 (For more information: Valvira). Finland has also introduced rules on neighbor smoking. These rules include a ban on smoking on all common areas of housing cooperatives and also the possibility of these cooperatives to apply to the municipality to ban smoking on all separate balconies of private apartments, outdoor areas, and even inside the apartments.
Astrid Nylenna’s contact info is included in the author affiliations at the top of this page.
Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

Surprise: Vitamin K2 and Cancer

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Micki Jacobs, Independent Researcher, Dayton, OH;
Email: mickijacobs@yahoo.com

Q: You know a great deal about Vitamin K2 and its precursors in human health and disease. What is the best evidence of any value of Vitamin K2, Menadione, Menaquinone-4, and Menaquinone-7 in the prevention or treatment of any forms of cancer?

A: Evidence and interest for benefits of vitamin K2 (K2) in cancer etiology and treatment are increasing. Menadione, vitamin K3, has been added to traditional treatments in response to findings that K3>K2>K1 in antitumor effects on various cancer cell lines, but K2 is garnering attention because it is not toxic at any dose, unlike known K3 toxicity. K2 in conjunction with traditional chemotherapy has shown benefits in vitro such as in Hepatocellular Carcinoma (HCC), pancreatic cancer, lung cancer, leukemia, prostate cancer, breast cancer and in a variety of animal models such as the rat model of HCC. Certain human patients have shown benefits with K2 supplements in terms of prevention and treatment; data show that more K intake reduces risk of all-cause mortality.
These forms of vitamin K–menadione (K3), MK-4, and MK-7 (the two most studied forms of vitamin K2 of about 14 identified K2 forms) are part of the larger vitamin K family which also includes vitamin K1, the K form found in plants. Whereas K1 and K2 can be found in food, K3 is not, yet newer findings show that the human body makes menadione from consumed vitamin K in a complex process leading to body-wide endogenously created MK-4, with possible interesting connections to cancer suppression involving the enzyme UBIAD1, dubbed a ‘tumor suppressor,’ essential in this conversion of K3 into K2 and which also controls cellular cholesterol and calcium metabolism.
Vitamin K has been postulated as among the various micronutrients whose subclinical insufficiency may lead to “diseases of aging” which includes cancer. In the Triage Theory, short-term essential processes utilize micronutrients to ensure immediate survival while long-term subclinical insufficiency leads to insidious diseases of aging. Seventeen vitamin K-dependent proteins (VKDP) require K sufficiency to be optimally activated, with coagulation as short-term essential, while VKDPs beyond the coagulation cascade may remain inactivate over time, leading to disease. It appears that subclinical vitamin K insufficiency is common and there is currently no clinical test for this. One of the many VKDPs that require K sufficiency to be activated is TGFBI – mice with this protein knocked out spontaneously manifest cancer and its expression is disrupted in various cancers as either over- or under-expressed. The various VKDPs appear to have multiple roles in cancer etiology, where K may offer disease preventative effects or disease promoting effects, depending on whether cancer has initiated or the stage in which the cancer has advanced.
K2 has become more of a consideration in cancer treatment after the success in turning melodysplastic syndrome (MDS) cells into healthy cells and preventing cancer. MDS is dominated by elderly (who often do not tolerate chemotherapy well) so higher dose MK-4 was used in a 65-year-old Japanese patient whose peripheral blood blast cells had increased to show progression to acute leukemic phase. Treatment with MK-4 offered benefits of reduced blast cell count and increased platelet count with no side effects leading to speculation that “suggests the clinical benefit of using non-toxic VK2 for the treatment of MDS, especially in elderly patients.” K2, sometimes in conjunction with vitamin D, was explored with other types of cancer cell lines. In 2002, K2 intervention was expanded to more MDS patients with various forms of refractory anemia where some were given menetetrenone v none. The benefits of intervention v none were mixed, but the fact that there were significant benefits of K2 with no toxicity led to further consideration of many cancer lines.
In the case of HCC, MK-4 inhibits cancer cell lines growth. K2 showed preventative effects in women with cirrhosis at high risk of HCC in a small randomized controlled trial (RCT). HCC is plagued with recurrence, and in a double-blind RCT of ‘cured’ HCC patients comparing placebo/45 mg/90mg/d MK-4, treatment did not offer benefits at any dose. The mechanism of HCC growthappears to involve PIVKA II, produced by HCC cells in the absence of vitamin K, and suppression appears to inhibit HCC. Unfortunately, administration of MK-4 increases PIVKA II and because HCC tumors are low in vitamin K, a newer way to directly administer K2 to cancer cells was tested and found to overcome their low menaquinone uptake and offer a potentially long-term, safe anti-tumor agent, a prodrug of menahydroquinone-4, a ‘pre-form’ of MK-4. This prodrug showed benefits in HCC mice models with significant tumor inhibition and substantial decrease in PIVKA II.
Micki Jacobs’s contact info is included in the author affiliations at the top of this page.
Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

Precision Medicine in the Universal Healthcare System in the Netherlands

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Jack A. Schalken, PhD, Professor of Experimental Urology, Radboud University Medical Center, Nijmegen, NL
Email: Jack.Schalken@radboudumc.nl

Q: Science is universal but the practice of medicine varies widely by geography, economics, and culture. The Netherlands is an advanced developed country with universal healthcare. How does your country approach the issue of precision or molecular oncology?

A: The Netherlands, a country with approximately 17 million people, has a typical socialized healthcare system, i.e. equal access to state-of-the-art medical care for all Dutch citizens, including but not limited to oncological care. This healthcare system was the basis for a rather unique effort towards precision molecular oncology. While molecular tumor boards were being established, a Nationwide initiative started in 2014, named Centre for Personalized Cancer Treatment (CPCT). Physicians can enroll patients in CPCT in 50 medical centers in The Netherlands, including all academic cancer centers. Cancer biopsies, preferably from metastatic sites are snap frozen and sent to a centralized state-of-the-art sequencing facility that was made possible via a donation of the Hartwig Medical Foundation. In case actionable mutation(s) are identified, targeted treatments can be prescribed, which is enabled/specified in the Drug Rediscovery Protocol (DRUP). Methodological concerns around Next Generation Sequencing (NGS) such as, quality of tumor specimen, standardized operating procedures (CLIA/ ISO certified laboratory), bioinformatics’ pipelines for mutation calling, and physician reporting are all addressed. Around 2,000 patients have been enrolled, and we are awaiting results from this unique effort to systematically introduce NGS-based DNA analysis into clinical practice. I believe the CPCT approach is the way forward. However, we should realize that this is only the first step towards precision medicine. One improvement is straight forward: molecularly characterize the cancer as early as possible since clonal heterogeneity is a well-described complicating factor in the treatment of this disease. We should not ignore it in our treatment concepts (i.e. combination treatment). In addition to epigenetic changes, changes in gene and protein expression harbor the key to molecular classification of cancers as basis for rationalized treatment. I will keep you informed on CPCT’s progress at CollabRx.com.

Jack Schalken’s contact info is included in the author affiliations at the top of this page.
Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.