Leave a comment to let us know what you think about the comments of Dr. David Agus comments on cancering.

Extreme Fatigue is one of the most common complaints heard from patients during chemotherapy treatments but there are ways to help alleviate this uncomfortable side effect without adding additional medications into their day. Numerous studies have shown the merits of exercising throughout treatment to help maintain a normal level of activity. These studies have also shown that continuing to follow an exercise program after treatment may help cancer survivors maintain a quality of life similar to that found before diagnosis.

Exercise can do more than just help reduce fatigue. It can also help many patients address the emotional issues that come with a cancer diagnosis and treatment. Issues such as weight gain, muscle loss, and postoperative healing can create a distorted body image, which may lead to depression. It is widely known that exercise can aid in weight loss and that weight bearing exercises can increase muscle mass but during exercise, the body also releases endorphins that create an elevated mood. This elevated mood could help patients see their situation in a more positive light and aid in their recovery.

Although some form of activity is recommended daily, each patient will require a different exercise program dependent on his or her disease and current treatments or if they are currently in a survivorship plan. For example, a patient receiving Mesothelioma treatment must be more cautious of activities that apply a greater strain on the heart or lungs while a patient being treated for Bone Cancer would avoid any high impact exercises that could lead to a fracture.

Because of these risks, many people choose to have a trainer help them design an appropriate exercise routine. This is a wonderful idea but it is important to remember that the trainer must understand the specific requirements of cancer patients. According to an article published on the National Cancer Institute’s website, the American Cancer Society has developed a certification program for trainers wishing to help cancer patients and survivors. This program ensures that cancer patients and survivors are receiving the best care possible.

by David Haas. David is a writer for the Mesothelioma Cancer Alliance.  Please follow David on Twitter @haasblaag.

Certainly don’t go out and start using all the drugs mentioned in the interview, but it is fun to watch and get you thinking.  Enjoy.

You may also like these previous posts:

Aspirin:  Should You Take One a Day?

Statin Side Effects:  Add Type 2 Diabetes

This book nicely discusses the issues of overdiagnosis in both chronic disease and in cancers.  The long-held assumption that all malignancies left untreated progress, spread and lead to death is simply not true.  We are learning that many types of cancer have unpredictable courses.  Prostate cancer is the most notorious of these, with good evidence showing that most prostate cancers are ones patients live with asymptomatically whether they know about them or not and die of something else without ever having symptoms of the prostate cancer. This is the primary issue behind the recent USPSTF “D” recommendation against routine PSA screening in asymptomatic men. There is strong evidence that some percentage of renal cell cancers, some types of breast cancer and thyroid cancers not infrequently regress or remain indolent and never lead to symptoms.

The recent evidence suggesting frequent overdiagnosis in breast cancer is very disturbing. An April 3 article in the Annals of Internal Medicine in a large retrospective review in Norway infers a 15-25% incidence of overdiagnosis in women found to have breast cancer on mammographic screening. They used every other year screening, and suggest that for every 2500 women screened 6-10 cases of overdiagnosis occurred, 20 women were diagnosed with breast cancer that was not overdiagnosis, and 1 death related to breast cancer was prevented.  We have strongly encouraged women to get annual mammograms for years. Personal anecdotal experience can make us even more confident that we are doing the right thing.  I have had many patients diagnosed with early breast cancer by mammogram over the last 20+ years, and until recently had not had any women over age 40 that I can recall diagnosed with advanced stage breast cancer who had been getting their annual mammograms.  It was very intuitive and tempting for me to believe that I was saving many lives and preventing much morbidity by aggressively pursuing early breast cancer diagnosis.  I know that I have put many women through emotionally stressful and uncomfortable additional testing, biopsies, and breast cancer treatment.  It is concerning to think that I may be subjecting some of these women to overdiagnosis and unnecessary treatment, but until we as a society actively address the issue of overdiagnosis and try to find ways to figure out which early cancers found on screening can be managed with active surveillance and which need curative treatment we are left with the inevitable overdiagnosis dilemma. This will  involve asking a cohort of women with various very early cancers to be observed for progression prior to intervention.  Whether this is going to be acceptable is not clear.  We need to do the same thing for men with early prostate cancer.  We are following lots of men with prostate cancer, but as far as I know not in a formal study that will give us help in knowing which cancers can be safely followed.  For now I’m doing nothing different except keeping my eyes wide open to further research and recommendations.

Much of what we do in medicine today is aimed at early diagnosis of asymptomatic disease, and overdiagnosis is a very valid concern any time we are screening for asymptomatic disease. The recent changes in criterion for hypertension, diabetes and hypercholesterolemia are leading us to the preventative treatment of many diseases that are of themselves asymptomatic.  The whole issue of overdiagnosis is going to be fascinating to follow over the next decade or two.

You may also enjoy:  PSA Controversy Continues

Eat: I too often see patients in acute grief with superimposed upper abdominal pain that I am certain is from gastric hyperacidity and not eating. Simply forcing yourself to eat can go a long way towards getting through a period of grief without complicating peptic ulcers or gastritis. I tell patients that they don’t have to be hungry, don’t have to feel like eating, and don’t even have to eat an extremely healthy diet. They just have to force themselves to chew and swallow a reasonable amount of food three times a day. Tradition in many communities, religions and cultures bears out the importance of eating. It is a nearly universal custom for family, friends and relatives to bring meals to the bereaved.

Sleep: Sleep is very difficult for many people in times of great stress or grief. In my opinion this is one of the most important times for physicians to prescribe sleep aides. It is tough to maintain your sanity and move through the rituals, responsibilities and duties expected when you are reasonably rested. In a sleep deprived state this is nearly impossible. Don’t be afraid to ask your physician for help if sleep is a problem after a major loss.

Carry On: This is my way of saying that forcing yourself to participate in at least some of your usual daily activities is very helpful in regaining some sense of normalcy. If you stay home all day, only see others who are also grieving, and don’t force yourself to carry on with your usual life activities it is too easy to become all-consumed by your grief. If you exercise normally continue to exercise. If you go to church continue to go to church. If you are in a service club, a book club, a bowling league, or other routine activity try to get back into that activity reasonably quickly. It can really help as a distraction and start to lead to a feeling that life can and must go on after the loss.

There is much more to managing grief, and I’m certainly no psychologist. Still, the advice to eat, sleep and carry is a good base on which to base your recovery.

Why don’t I do a better job?  I suspect it is a combination of factors.  I think the first is that this is rarely high on a patients list of topics they want to discuss at an office visit.  It is easy to put off this discussion when seemingly more pressing issues are the patient’s expressed reason for the office visit.  Even at physical exam visits, or in the medical coding lingo “preventative care” or “health maintenance” visits, it is alluring to focus on topics that lead to a longer or healthier life rather than a better death experience.  Here is the list of the physician-related barriers to completion of an advance directive listed in the AFP article:

• Discomfort with the topic.
• Lack of institutional support.
• Lack of reimbursement.
• Lack of time.
•  Waiting for the patient to initiate the discussion.

In my case it is certainly not discomfort with the subject, and I am not intentionally waiting for the patient to bring up the subject, but lack of time and reimbursement undoubtedly play a role.

In addition most patients really don’t need my help in working through this decision process if they address the issue before there is a crisis. Although there are cultural, personal and ethnic variables that shape our decision making, most of my patients can  really quite quickly and easily work through the process of completion of both a very functional living will and a durable power of attorney without my assistance.  So why doesn’t everyone just do it themselves?  Here are the barriers listed in the AFP article that are patient related:

• Fear of burdening others, i.e. family or friends.
• Health Literacy
• Lack of interest or knowledge of the subject.
• Spiritual, cultural or racial traditions.
• Waiting for their physician to initiate the discussion.

So how can you just “Do it yourself?” It’s really easy.  Obvoiusly since you are reading this article you have access to the internet, and everything you need is just a few clicks away.  I encourage you, if you have not already completed these documents, to DO IT NOW:

1. Down load your state’s Advance Directives at the caringinfo.org site.  This is really easy and you can get everything you need by selecting your state from the list here.
2. Many states have a form called a POLST form.  This stands for physician orders for live sustaining treatment.  If you use a search engine like Google, and you type in your state + POLST form you will easily find a form to download if your state has a POLST form.  You can get the Washington State form to download easily at WA POLST download.  Many physician offices have these available, just ask your doctor.
3. For some people a form to help you ascertain your values on this subject and to make your values clear to the individual you choose to have your medical power of attorney is helpful.  The University of New Mexico  Institute for Ethics has published online a non-copyright protected form for you to download.  Some patients will find it helpful to attach this to their advance directive as guidance to their proxy in making decisions in line with their values.

There you have it.  You have no more valid excuses to keep you from completing your own advance directive and living will.  Once you complete it be sure to not keep it a secret.  Give a copy to your physician, to the person you choose as your DPA, and keep a copy handy at your home.   Don’t be a victim of your own procrastination or discomfort with this topic.  If you find it helpful ask questions on the subject up with your personal physician.  Be sure to let them know you have these documents completed.

In my best cheer-leading mantra:  You can do it!  Go – Go – Go!

Weakness that I don’t think of as being asthenia on the other hand is usually used to describe a loss of muscle strength that is localized or if generalized is not associated with overall wasting or other symptoms of advanced disease. Weakness can be associated with neuromuscular disease like a nerve root impingement, a stroke or other brain lesion and other causes that lead to true loss of power in one or more muscles, or can be more a perceived weakness where patients feel they need to exert more force than normal, but on testing muscle strength is normal. Disorders like chronic fatigue syndrome and depression can lead to perceived weakness

A specific disorder called myasthenia gravis is a condition where strength at rest is normal, but with repeated use muscle strength decreases. It is due to an autoimmune disorder where antibodies against the post-synaptic acetylcholine receptors at the neuromuscular junction are blocked.

Numerous medications have asthenia as a potential side effect. The HIV drug Ritonavir which functions as a protease inhibitor has been associated with asthenia. This has to be somewhat of a dilemma as progression of HIV itself is a potential cause of asthenia. Chronic opioid use for pain management has been linked to asthenia in some individuals. Alcoholism is a common cause of asthenia, as are other types of drug abuse. The list of potential medication causes of asthenia is long, and medication use always needs to be considered in a patient presenting with undiagnosed asthenia.

Still in my practice, admittedly a suburban practice where neglected disease is relatively uncommon and HIV is not a major part of my practice, advanced age, end stages of serious illnesses, and cancer are the most common causes of asthenia. As patients become very old it is common for them to lose strength and body mass and whether this is asthenia or not may be up for debate. Asthenia associated with weight loss is a fairly common presentation of undiagnosed cancer. Asthenia is fairly common with end stage cirrhosis and liver failure, with very severe congestive heart failure and with COPD as respiratory failure approaches. In most cases unless a diagnosis can be made with good treatment options asthenia is a serious if not ominous symptom.

I have to say I rarely describe a patient as having asthenia, but when I do it is with the intent of trying really hard to find an underlying cause that can be treated or at least discovered, because asthenia in my mind is usually something that needs to be figured out.

How Doctors Die by Ken Murray a FP at USC.  

It is largely anecdotal, but is a really an interesting perspective on how at least some physicians choose to forgo futile end-of-life treatments because they know the limits of modern medicine first hand.

Also Enjoy:

Octogenerian’s Letter to Santa

Add Some Red to Black Friday and I’ll give some Green to the American Cancer Society

Millions of Americans shop for Christmas gift bargains on Black Friday every year.  I encourage you to give a gift on Black Friday that costs you nothing more that a little time, and which can help you feel you have truly given life and hope during this holiday season.

My readers will know that I’m a big proponent of regular blood donations.  Kay, my wife has ovarian cancer and has been a recipient of donated blood when her blood counts get low from chemotherapy.  Cancer patients are among the highest users of donated blood products from red blood cells to platelets.  I’m donating regularly to be sure our family puts more blood into the blood banking system than we take out. I want you to join with me on the Friday after Thanksgiving this year by paying a visit to your local blood donation center.  There are even potential blood donation health benefits.

I’m putting out a challenge to readers, your friends and anyone else you can contact.  Black Friday is a day when many of us are out and about shopping and getting ready for the holidays.  The holiday season is also a time when blood donations tend to fall behind need.  Here is the challenge:

I’ll donate $1. (up to $1000) for every comment to this post or tweet me @DoctorPullen telling me that you have or intend to go to your local blood donation center on Black Friday and donate blood. $1. may sound like chump change, but I want to get 1000+ people who would otherwise not donate blood to do so this Friday.  We are in a world of easy communication, and I bet everyone who reads this knows 10 people who are in a position to get to their blood donation center this black Friday and donate.  Just do it!

Take a break from shopping, get off your feet, and relax while you give one special holiday gift.  Use the twitter or facebook links to send this off to your friends, tell your coworkers, shout from the roof tops, whatever but let’s make this Black Friday blood red with our generosity.

My daughter, son and I plan to go to the local Cascade Regional Blood Bank center in Puyallup Friday. I checked and they are open 7:30 AM – 5:00PM.  I’ll try to keep a counter going on the site to let you all know how we are doing.

They Turned Me Away Today

Egg on my face.  I went today to donate, but was turned away because I went to Belize on vacation a couple of months age, an area with malaria exposure potential.  I’m now ineligible for a year, joining a majority of the rest of Americans.  If you are among the 37% who are eligible donors get to your blood donation center and give.  Keep our blood supply safe and plentiful.  Happy Thanksgiving.

Don’t miss a post.  Subscribe using the right sidebar feature.

You may also enjoy:

Actual Causes of Death in the U.S.: Not What You’d Think

Leading Preventable Cause of Death in America

Can Cancer Ever Be Ignored?  by Shannon Brownlee and Jeannie Lenzer

I especially like the article’s visual.  It raises the seldom stated but often considered axiom that every good primary physician knows:  If you don’t want to know the answer, don’t ask the question.

Dr. Kenny Lin, a key player in the PSA debate as the ex-USPSTF point investigator on the PSA screening dilema who resigned in protest of political pressure to withhold new recommendations to make PSA screening a grade D (as in don’t do it) for PSA screening in healthy males that was based on the best available evidence but was politically unacceptable writes another excellent discussion of the topic:

The Meeting that Wasn’t Revisited by Kenny Lin MD.

Stay tuned for the latest on this controversy.  Subscribe to DrPullen.com to not miss a post.  You can choose to subscribe to all posts, or just by category.  Just enter your e-mail address in the subscribe area at the right.

NOTE THAT SINCE THIS WAS POSTED THE USPSTF HAS POSTED A PROPOSED UPDATE TO THEIR RECOMMENDATIONS FOR PSA TESTING FOR MED AS A “D” RECOMMENDATION, i.e. RECOMMENDING AGAINST USE OF PSA AS A PROSTATE CANCER SCREENING TOOL.

by Patrick Maguire, MD 

As we near the end of Prostate Cancer Awareness Month this September, hopefully many of us have learned a thing or two that we didn’t know about the disease in August. Just last week, a major study of predictors of sexual function after prostate cancer treatment was published in the prestigious Journal of the American Medical Association (JAMA). I found some important info in the paper and recommend it highly to men who are considering their options for treatment. The link for the full document is:  http://jama.ama-assn.org/content/306/11/1205.full.pdf. An in-depth discussion of the topic can be found at on my blog The Cancer MD. As opposed to various treatment choices, one option for men after a prostate cancer diagnosis that we don’t hear too much about in theU.S. is active surveillance.

Many terms have been used to describe what is now most often called active surveillance. These include: watchful waiting, close observation, and expectant management, among others. Given the right circumstances, the option of avoiding prostate cancer treatment altogether is often best. Which men are candidates for watchful waiting after their diagnosis?

To be sure, prostate cancer is a spectrum of disease that can range from indolent to extremely aggressive. Men with low-risk prostate cancer may be good candidates for no immediate treatment. These cancers can’t be felt or are only felt in part of one side (lobe) of the prostate, produce a low level of prostate specific antigen (PSA) in the blood, and appear not too aggressive under the microscope (Gleason score of <7). Among this group, younger, healthier men are usually the best served by treatment.

Men with low-risk disease who are either older or in poor overall condition should strongly consider expectant management. In general, it takes more than a decade for early prostate cancer to spread to other sites in the body (metastasize) and ultimately kill a man. Therefore, men who have a life expectancy less than 10-15 years should think long and hard about the option of no treatment. In medical school, we docs agree to abide by the Hippocratic Oath, a major principal of which is “primum non nocere” (do no harm). We don’t want to put a man at risk for possible side effects of treatment, unless we have reason to believe that the treatment has a good chance to improve survival or quality of life.

So, if you or your loved one has been diagnosed with prostate cancer that’s found very early, ask your urologist or radiation oncologist whether active surveillance or watchful waiting is a reasonable option. Sometimes, though it may feel strange, you might have to tell him or her, “Doc, don’t just do something. Stand there!?

Dr. Maguire regularly posts on TheCancerMD.com and is the author of a book that I have enjoyed reading that helps laypersons understand the language, facts and treatment options for the most common cancers. When Cancer Hits Home: Cancer Treatment and Prevention Options for Breast, Colon, Lung, Prostate & Other Common Types. 

What is Hospice?

Hospice is not a death sentence. It is an opportunity to live life to the fullest until you die.

I have been a Hospice volunteer since 1994. It is my passion. To be of service to others during such an important and intense time of life is an honor. The more I give, I am repaid tenfold. In order to qualify for Hospice a patient must be  diagnosed with a terminal illness that if it were to progress at the normal rate, would only have six months to live. To be eligible a patient can’t be involved in treatment to try cure the illness. Their doctor must write a referral for the patient to be evaluated for Hospice care.

Once enrolled, if the patient lives to the six month timeframe they can be evaluated and reinstated in the program. Hospice provides many services that assist both the patient and the family. I have had many conversations with family members and friends of terminally ill patients who were anxious because of unresolved issues with the patient or because they just felt they needed to share something and had not done so. I always encourage them to make time to talk about the issues. It will be too late once the patient has passed. If left unresolved these situations can lead to the survivor feeling regret, sadness, guilt or frustration. Grief is natural but adding the pressure of not talking openly before someone dies can make the grieving process much harder.

Many patients have talked with me about the importance of relationships in their life. They have never expressed regret about wishing they had more money, possessions or fame. It is so important to most people to know that they don’t have any unfinished business, which allows them to pass peacefully. Once a patient has been diagnosed with a terminal illness, Hospice is the best way to have their wishes met. The Hospice team; Nurse, CNA, Chaplain, Social Worker, Medical Director, Volunteer Coordinator and Volunteers work together to accomplish the patients desires. This team effort helps address the patient’s complete needs; physical comfort, emotional and spiritual support. Treating the entire patient is very important. Then, after the patient passes the family has a great support system and grief counseling, and support groups available anytime there is a need. I have had many heart-to-heart talks with patients in addition to fun and silly times together. After every assignment I take time to reflect on the experience. I have always learned something from each patient. The patients and families have always thanked me and said how much my service and the Hospice services in general made a positive difference.

I encourage anyone interested in Hospice or in volunteering to call your local Hospice organization. If you have questions please contact me at christinalufkin1@yahoo.com. Christina is also available for interviews or guest speaking engagements. Christina Lufkin, Author “Live with Purpose:Die with Dignity” www.christinalufkin.weebly.com

Comments by Dr. Pullen:  Over the years I have had nothing but positive experiences with hospice.   When my Mom passed last spring Hospice was involved and they definitely made for a better experience all around. See my post, Saying Goodbye.  Hospice has several major advantages from a flexibility and financial standpoint also for terminal patients.  The Medicare reimbursement for Hospice is on a per-diem basis, and the Hospice team has a great deal of flexibility in choosing services to provide to patients, many of which would not be eligible for regular Medicare coverage.

You may also enjoy How We Fail and End of Life Care.

An argument can be made that knowing when not to do screening for a disease or condition is as important as knowing when to do screening.  The USPSTF makes recommendations to physicians and patients about what screening preventative services should be done in asymptomatic patients, and which should not be done routinely. The USPSTF is an evidence based decision making body. They carefully review the evidence and make recommendations for or against screening based solely on the available evidence which helps keep emotional and arbitrary recommendations from becoming the mandate. The recommendations are separated into 5 grades:

• A Recommendation: The USPSTF recommends the service. There is high certainty that the net benefit is substantial.
• B Recommendation: The USPSTF recommends the service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial.
• C Recommendation: The USPSTF recommends against routinely providing the service. There may be considerations that support providing the service in an individual patient. There is at least moderate certainty that the net benefit is small.
• D Recommendation: The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits.
• I Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined.

I thought it was timely to list a few of the screening services that the USPSTF recommends against, or finds insufficient evidence to make a recommendation for or against. This list is not intended to be comprehensive. See the USPSTF site for a complete list of their screening recommendations.
Cancer Screening Recommendations:

• The USPSTF recommends against routine testicular cancer screening in adolescent and adult males. D recommendation.
• The USPSTF recommends against routine ovarian cancer screening. D recommendation.
• The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of using a whole-body skin examination by a primary care clinician or patient skin self-examination for the early detection of cutaneous melanoma, basal cell cancer, or squamous cell skin cancer in the adult general population. I recommendation.
• The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of prostate cancer screening in men younger than age 75 years. I Recommendation.
• The USPSTF recommends against screening for prostate cancer in men age 75 years or older.  Grade: D Recommendation.
• The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for bladder cancer in asymptomatic adults.  Grade: I Statement.

Heart and Vascular Disease Recommendations:

• The U.S. Preventive Services Task Force (USPSTF) recommends against screening for asymptomatic carotid artery stenosis (CAS) in the general adult population.  Grade: D Recommendation.
• The U.S. Preventive Services Task Force (USPSTF) recommends against routine screening with resting electrocardiography (ECG), exercise treadmill test (ETT), or electron-beam computerized tomography (EBCT) scanning for coronary calcium for either the presence of severe coronary artery stenosis (CAS) or the prediction of coronary heart disease (CHD) events in adults at low risk for CHD events.  Grade: D Recommendation.
• The USPSTF found insufficient evidence to recommend for or against routine screening with ECG, ETT, or EBCT scanning for coronary calcium for either the presence of severe CAS or the prediction of CHD events in adults at increased risk for CHD events.  Grade: I Statement

Other Recommendations:

• The U.S. Preventive Services Task Force (USPSTF) found insufficient evidence to recommend for or against screening adults for glaucoma. I recommendation.
• The USPSTF recommends against screening adults for chronic obstructive pulmonary disease (COPD) using spirometry. D Recommendation

These recommendations are for screening in asymptomatic persons. They are not recommendations against testing for a disease in the presence or symptoms or other factors where making a diagnosis may alter management decisions.
At first glance these recommendations  may seem disappointing. Intuitively it seems like early diagnosis of cancer, glaucoma, coronary disease or chronic lung disease should lead to better outcomes. Unfortuntely the data does not lead to those conclusions. In some cases like prostate cancer screening the early diagnosis may lead to more morbidity and problems from testing and treatment than benefits of the earlier diagnosis provide. In other situations like screening for coronary disease screening the high incidence of false positive tests and the low prevalence of disease make screening impractical. In still other situations like COPD making the diagnosis does not lead to effective interventions that alter the course of the disease.
I am grateful that the USPSTF puts out these recommendations, and am hopeful that they will become more active again after political pressure of late seems to have slowed the pace of their production to a point where new recommendations are needed in important areas like PSA screening.

Tabex was reported in the prestigious New England Journal of Medicine to be more effective than placebo for help in quitting smoking.  Sounds great until you read the actual numbers.  Tabex was shown in a single fairly small study including only 740 patients that was conducted in Poland to have a 1 year success rate of 8.4% as compared to a 2.4% success rate with placebo.  Admittedly this sounds like it is helpful in a small percentage of patients, but at best only about 1 in 12 patients using Tabex will be successful in quitting smoking.

Still having an inexpensive and over the counter product patients can use to try to get help in quitting smoking is exciting.  Studies show that most smokers would like to quit smoking.  Smoking rates have decreased significantly in the United States over the last couple of decades, but many patients in my practice just cannot seem to quit smoking.  Chantix has been quite helpful for many patients, but significant Chantix side effects including cardiovascular concerns, vivid dreams, depression and even suicidality have been deterents to Chantix use. The high price of Chantix is also a major deterrent to widespread use.  Bupropion, originally marketed as Zyban for smoking cessation, is sometimes helpful, but far from a panacea.

Tabex, chemical name cytosine, is structurally similar to nicotine, and functions as a nicotinic acetylcholine receptor agonist.  It is an extract of the seeds of Golden Rain acacia (Cytisus laborinum) and Chantix is actually a derivative of cytosine and has been approved for smoking cessation in the U.S. since 2006.  Tabex has b een used in Europe for nearly 40 years for smoking cessation and has been produced by a Bulgarian company Sopharma AD.

In the NEJM study Tabex was used on a 25 day tapering schedule, taking 6 tablets daily for the first 3 days, five tablets on days 4-12, and then tapering more quickly by taking 4 days on 4/day, 4 days on 3/day, until stopping on day 25 after 2 days of two tablets daily.  At this dose toxicity seemed minimal, although the authors admit the study was too small to find uncommon adverse effects of Tabex.   Cytisine has been documented to have serious side effects at much higher doses, so users should not take more than this regimen used in the NEJM study.

Tabex appears to be inexpensive, on E-bay I found vendors selling #100 1.5 mg tablets for $13.35 USD.  This would amount to enough pills for a person to take the recommended 25 day regimen and have just a few pills left over.  This compares to Chantix which costs about $179/ month at Drugstore.com.

This small NEJM study implies that this inexpensive, seemingly fairly safe drug, available without a prescription, is marginally effective for helping smokers quit the habit.  I think it may be worth a try for smokers who have been unable to quit using nicotine replacement systems, cannot tolerate, cannot afford or have reasons not to use Chantix, and are motivated to quit.  The long term adverse health effects of continuing to smoke seem to far outweigh the risks of essentially all of the smoking cessation aides for patients without specific contraindications to their use.

In European use for over 40 years there does not seem to have been much in the way of serious problems with Tabex use, and I anticipate the use of Tabex to increase significantly in the U.S since the NEJM article has given more validity to its use.

There is really little to no evidence that the other SSRI drugs like citalopram or sertraline help patients to quit smoking.

The abstract of the NEJM article is available here.

The theory of testing cancer cells to see what drugs will be most effective is somewhat like the way we test the bacteria causing an infection to see what antibiotics work well to kill the specific strain of germ causing an individual patient’s infection. Bacteria are collected from the infection site and lab testing is done to see which antibiotics are most effective in killing those bacteria.  Crizotinib is a chemotherapy agent that is an inhibitor of the enzyme anaplastic lymphoma kinase (ALK).  Approved for use at the same time as crizotinib was a test called Vysis ALK Break Apart FISH Kit, made by Abbott molecular, that can be used to test the cancer cells to see if they express this specific enzyme.  If a patient with non-small cell lung cancer has cancer cells that express this specific enzyme, then crizotinib may be useful in targeting the cancer cells in those patient.  It would not likely be useful in patients where the cancer cells do not express the ALK enzyme.

Crizotinib is approved for treatment of advanced non-small cell lung cancer that expresses the ALK enzyme. The concept of choosing cancer treatments based specifically for an individual based on the characteristics of their cancer cells is very much in vogue and there is a good deal of hope for this type of therapy.  An example of this type of therapy is the use of PARP inhibitors in breast and ovarian cancer patients who have the BRCA gene mutations.  The theory in these BRCA 2 mutation positive patients is that since they lack the function of the BRCA gene that helps repair double stranded DNA breaks that inhibiting the PARP function that repairs single stranded DNA breaks will make cancer cells more susceptible to chemotherapy agents or the body’s own immune system.  Although this is somewhat less targeted than the crizotimib approach it is theoretically somewhat patient specific therapy.

In breast cancer patients testing the cancer cells for estrogen receptor status, and targeting estrogen receptor positive tumors for anti-estrogen therapy with tamoxifen and other drugs has been standard therapy for years.  New immunotherapy and antibody based therapies are also patient and tumor specific therapies.  The ideal of using chemotherapy targeted specifically at an individual’s cancer cells rather that lumping all patients with a given type of cancer into the same regimens of treatment is unique and seems to hold much promise.  Time will tell just how helpful crizotinib is for advanced non-small cell lung cancers that express the ALK gene, but this type of treatment where more specific therapy is targeted at an individual’s cancer cells is exciting and promising.

Although crizotinib is going to be targeted at a fairly small cohort of patients it is exciting to see the progress of personalized cancer therapy take one more step forward.

It will be interesting to see if use of the aromatase inhibitors for estrogen sensitive conditions other than breast and ovarian cancer becomes more widespread in future years.  Their difficult side effects of the aromatase inhibitors makes this less likely than if they were easy to tolerate.

Pancreatic neuroendocrine tumors are a completely different cancer.  They originate in the cells of the pancreas that produce insulin, the islet cells, and are often called islet cell tumors.  This cancer is in a family of cancers called neuroendocrine tumors that sometimes are found in families with hereditary predisposition to this type of tumors called MEN 1. (MEN stands for multiple endocrine neoplasia)

Mr. Jobs announced in a company e-mail in 2004 that he had undergone a successful surgery for an islet cell pancreatic tumor.  He underwent an extensive surgery to remove the pancreas and surrounding tissues called a Whipple procedure.  This is a very big surgery for some time he seemed to do well.  Over the last couple of years it appears that his health has been in decline, and this week he announced his resignation as CEO of Apple.

Pancreatic islet cell cancer is a rare type of cancer. There are about 2500 cases of this cancer diagnosed in the U.S. annually.  IN many cases of pancreatic islet cell cancer surgery can be curative, and aggressive surgery is often undertaken as was the case in Steve Jobs cancer.  These tumors can be either benign or malignant.  In Steve Jobs cancer it was malignant.  The islet cells produce several hormones, including insulin, gastrin and others.  When the tumors are functioning to make one of these hormones the symptoms can be very dramatic.  Insulinomas, tumors that produce insulin, can produce severe and refractory hypoglycemia.  Tumors that produce gastrin, the pancreatic hormone that leads to gastric acid secretion in the stomach, gastric and duodenal ulcers that are recurrent and refractory to treatment can occur.  This is sometimes called Zollinger-Ellison syndrome.  Measurement of serum insulin levels or serum gastrin levels can help in the diagnosis of these tumors.

I bought my first Macintosh computer in 1988 and love my iPhone today.  Although I use a PC for most of my day-to-day work, I do love Apple products, and it has been fun to see the ups and downs of Apple and Steve Jobs over the years.  Mr. Jobs has been a controversial, colorful and undeniably brilliant force behind Apple computer, and it is sad to see him leave the company at a relatively young age because of health concerns.  I hope his prognosis is better than it appears and will certainly add him to my prayer list.

Pruritus without a primary dermatologic etiology is definitely more concerning.  When I see pruritus of this type the duration of symptoms and the history and physical exam are the keys to deciding whether to simply treat the itching with medications or to do further diagnostic evaluation.  Pruritus is common enough that if symptoms are only a few days in duration and there are no obvious clues on history suggesting an underlying problem and nothing on a directed physical exam raises red flags treatment with a non-sedating antihistamine like cetirazine (Zyrtec, check Zyrtec side effects) or loratadine (Claritin) is often tried.  If a patient has had symptoms for more that 2-3 weeks usually a lab evaluation looking for diabetes, liver or kidney problems, thyroid disease and hematologic malignancies is done.  About 14-24% of patients that are referred to dermatologists with pruritus without a skin disorder have a systemic condition causing the pruritus.  The list of potential systemic causes is very long but includes:

• Hematologic causes like hemochromatosis, iron deficiency anemia, polycythemia vera and various blood dyscrasias.
• Liver and bile duct problems like cirrhosis, sclerosing cholangitis, drug-induced cholestasis, and viral hepatitis like Hepatitis C.
• Cancers like lymphomas, especially Hodgkin’s Disease, leukemia, multiple myeloma and many solid tumors.
• Endocrine disorders like hypothyroidism, hyperparathyroidism, and diabetes.
• Metabolic disorders like chronic renal disease.
• Neurologic problems like multiple sclerosis, stroke and brain abscesses and tumors.
• Autoimmune disorders like dermatomyositis, Sjogren syndrome, and others.
• Infections like AIDS and parasitic diseases.

If a patient has a normal complete blood count, metabolic profile with a fasting  blood sugar, TSH to exclude thyroid disease, and no primary dermatologic cause often I will get a chest x-ray to check or enlarged lymph nodes in the chest as a clue to lymphoma.  If this is negative I will usually treat their itching for a few weeks.  If they persist with pruritus I may refer them to a dermatologist or an allergist for further evaluation.  Most of the time fortunately no serious causes is found. Still enough of the time they have a  more serious underlying cause that pruritus lasting for more than a few weeks without an apparent cause is a symptom physicians respect and look diligently to solve.

Currently sunscreen labels are graded for protection against ultraviolet B spectrum rays (UVB) which is the frequency of rays that causes sunburn.  For this reason the strength of the UVB protection is called Sunburn Protection Factor (SPF) and is graded from 2 through 50.  SPF 10 is less effective than SPF 15, which is less than SPF 30 etc.  The new FDA proposal is for sunscreen to also have a rating for protection against Ultraviolet A frequency radiation (UVA) which penetrates the skin more than UVB and leads to more tanning.  UVA frequency rays also cause skin cancer, so you cannot assume that by tanning but not burning you are avoiding skin cancer risk.  In fact despite increased use of sunscreens and increased awareness of the need for UV ray protection the incidence of malignant melanoma has doubled since 1973, although the death rate from melanoma has remained essentially stable over the last 10 years.  This may be due to increased awareness and early diagnosis with more diagnoses being of more superficial lesions, or may be to overdiagnosis.

The new FDA proposal calls for some revisions to the SPF ratings, and adding a star system for UVA protection.  The stars will stand for :

• * one star            = Low protection from UVA rays.
• **two stars         = Medium protection from UVA rays
• *** three stars   =  High protection from UVA rays
• ****four stars    = Highest UVA protection available in an OTC product

Here is the proposed labeling from the FDA site:

As summer approaches remember that even using the best available sunscreens is only somewhat protective against damaging radiation.  In addition to sunscreen pay attention to these additional methods of protection:

• Wear sunglasses.  Make sure your sun glasses give UV light protection.  Some designer fashion glasses may not.
• Protective clothing is the best way to keep the sun’s damaging rays off you skin when you are in the sun.
• Try to avoid direct midday sun when the rays pass through less atmosphere and have the most intensity.
• Reapply sunscreen frequently. Every 2 hours is recommended, and use adequate amounts.  I very thin layer is not as effective.  Until the new labeling takes effect, choose a brand of sunscreen that claims a broad spectrum protection, to get UVA protection as well as the UVB protection the SPF factor signifies.
• Remember that tanning is at least as dangerous as sunlight, and though you may like the appearance of a “healthy tan” it really is far from healthy.

Enjoy the summer sun, but protect your skin.