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.

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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.

First is to recognize that constipation is extremely common when you take these medications. In one large meta-analysis 41% of patients using potent long-term opioids experienced constipation. In another less rigorous study 95% of patients interviewed by oncology nurses reported constipation as the most common side effect of their pain medication management. So if you need to use pain medication, expect to need to deal with constipation. Don’t wait until you are in terrible pain and have not had a stool in days to begin managing the problem.

The body has at least three opioid receptors. One of these, the mu receptor is not only in the brain where they modulate pain perception but also in the bowel. In the bowel stimulation of the opioid mu receptor leads to increased activity of the circular muscles and decreased activity of the longitudinal muscles. This results in increased churning of the bowel contents and more fluid resorption, and less propulsion and movement of the bowel contents. The net result is dryer, harder stool that moves more slowly and efficiently through the bowel. The anus also has opioid mu receptors, and the tone is increased, leading to less reflexive relaxation in response to stool distending the rectum, and so it is more difficult to have a bowel movement. One note of interest is that the dose of opioids needed to induce constipation is considerably less than the amount needed to treat most pain, so even low doses of opioids can lead to severe constipation.

Because of the mechanism of opioid induced constipation treatment and management is different from the management of ordinary functional constipation. Bulk producing products like psyllium, benefiber, and Citrucel are not helpful and should be avoided. Stool softeners like docusate can be helpful but need to be used in combination with a stimulant. Stimulants which are best minimized in functional constipation are a mainstay to the management of opioid induced constipation, and are usually best combined with a gentle stimulant like senna. Senna is available in a combination product with a docusate as Senokot – S, and generic versions of this produce are available without a prescription.

In my patients I often suggest taking about ½ of a Senokot-S tablet for each 1 dose of oral opioid, and then adjust up or down as needed. It’s key to start this before becoming terribly constipated, as catching up is very difficult.

A newer injectible drug methylnaltrexone (Relistor) is an antagonist to the opioid mu receptor that does not cross the blood brain barrier and can be used in extreme cases of opioid induced constipation. Methylnaltrexone use is limited by its cost and the fact that it needs to be injected.
Overall the key to management of opioid induced constipation is recognition of the problem early, appropriate use of laxatives like senna and docusate, and avoiding opioid use when possible.

See related posts:

Oxycontin vs. Oxycodone

Can’t Find a Doctor to Prescribe Pain Meds?

April 11, 2011, 5:24 PM

A Couple’s Knot, Tied Tighter by Dual Diagnoses

By TARA PARKER-POPE

This patient had presented to our same day clinic three days previously, and had liver function tests as well as testing for hepatitis A,B and C, as well as an abdominal ultrasound ordered.  The LFTs showed significant elevation of the transaminases, a bilirubin of 5.6, and the tests for viral hepatitis were all negative.  The ultrasound added some hope with a gall bladder full of stones, but no common bile duct stone seen on the scan, and the common bile duct was dilated to 16 mm, far larger than normal.

The anatomy of the outflow of bile from the liver and gall bladder is fairly simple to think about, and the pancreatic duct empties into the common bile duct near where the cystic duct from the gall bladder joins the common bile duct.  The head of the pancreas is near this area, and cancer of the head of the pancreas can cause obstructive jaundice of the bile duct.  Cancers of the gall bladder or common bile duct can also cause jaundice as a presenting symptom.  Cancers metastatic to the liver can also cause jaundice by obstruction of intrahepatic bile ducts.

I’m praying that this patient has a common bile duct stone and obstruction that can be cured with removal of the stone and cholecystectomy, but know that it is likely that the stones are not the problem.

Other causes of jaundice include the many types of cellular inflammation of the liver called hepatitis, overly rapid breakdown of red blood cells called hemolysis that can overload the liver with hemoglobin that is metabolized into bilirubin and can lead to jaundice, bile duct disorders like the autoimmune disorder called primary sclerosing cholangitis, and other causes of bile duct obstruction.  Still common things being common I am anxiously awaiting word from my gastroenterology consultant on the results of the ERCP (endoscopic retrograde cholangiopancreatography- a test where a scope passed through the stomach into the duodenum is used to inject dye into the bile and pancreatic ducts) to see what is causing my patient’s jaundice symptoms.

This week the MMR put out its press release outlining a program in Minnesota from 1999-2010.  Over that period of time Minnesota maintained a sustained effort to reduce cigarette smoking, and has some degree of success.  Tobacco addiction is a terrible problem in the US, and increasingly worldwide.

In Minnesota over this period of time they instituted provision of statewide smoking cessation programs, a comprehensive smoke-free law, increased tobacco taxes and had mass media campaigns.  During this time Minnesota outperformed the rest of the US by having the prevalence of tobacco use in adults drop from 22.1% in 1999 to 16.1% in 2010, a 27% drop, compared to very modest reductions nationwide. (1)

This may seem modest, but Minnesota is a fairly large state with a population of 5.27 million, and an estimated 3.87 million adults. This means about 231,900 less Minnesota adults smoke now than smoked in 1999.  I had a hard time coming up with data to estimate the number of life years saved by this campaign, but if the smokers who quit reflect the demographics of the adult population in MI and using the excess death data from 2004 BMJ British physician study (really a rough estimate I know) then about 2,085,000 life years were extended to the citizens of Minnesota as a result of quitting smoking in this time frame.

If the entire US replicated this program, and had smoking cessation rates that match those in MI then by extrapolation we could add about 122 million years to the lives of Americans over a 10 year period if 6% less Americans smoked after the program.

When I think if the dollars spent to add a year of life by many medical interventions, this type of program seems like it would be a bargain.  One study suggests that for every $1.00 spent on tobacco cessation a state saves $1.26 in lost revenue from work missed and tax revenue.  If that’s true then states can actually improve their bottom line while they improve the health of their citizens.    Sounds pretty good to me.  Smoking may not seem like a drug addiction, but it most certainly is in many cases.  By boning up on addiction treatment information online, you can put yourself in a position where you can help a relative or a friend deal with their drug addiction.

Merry Christmas

I’ve decided what I want for Christmas this year.  I want the court rulings from 2009-2010 on the Myriad Genetics company’s BRCA gene patent for BRCA gene testing to be upheld and to become law.  Those of you who are new to DrPullen.com you may not know that my wife has a BRCA2 gene mutation and is living with cancer of the ovary, currently on treatment in a clinical trial including a PARP inhibitor.  She was diagnosed with this mutation by use of the genetic testing licensed by Myriad Genetics and the University of Utah.  I was essentially unaware of the whole controversy over licensing of the human genome prior to Kay’s diagnosis, but have been much more passionate about how wrong is and how badly this can affect patients, their families, and adversely affect medical research since then.

The BRCA gene was isolated and cloned at the University of Utah in 1994.  The same year Myriad Genetics was formed, a patent filed for the BRCA 1 and subsequently BRCA 2 genes was filed.  The first patents were granted in 1997 and 1998.  Currently Myriad provides the only available testing for BRCA 1 and BRCA 2 gene mutation testing.  The patents for this testing and for the patent on the BRCA 1 and 2 genes held by Myriad have been challenged in court with lawsuits supported by patients, physicians, medical associations and the ACLU.

In a somewhat surprising set of court rulings in the case of Association for Mollecular Pathology et. al. v. United States Patent and Trademark Office a motion to dismiss the case was denied on Nov. 1, 2009.  Subsequently on March 29, 2010 Justice Robert W Sweet ruled in US District Court in NY that the patents on the BRCA 1 and 2 genes are invalid.  Of course this has been appealed by Myriad to the US Court of appeals.  This will be a very interesting case to follow, as its outcome may go a long ways towards setting a direction for the whole field of genetic patents.

Currently 20% of the human genome is patented.  The impetus to overrule the Myriad BRCA gene patents has been energized by the arrogance with which Myriad has defended their monopoly on testing for this gene’s mutations.  The fact that they charge $2975 for this testing adds to the anger by patients and physicians.  Myriad has refused to allow use of their testing to assess the accuracy of the test itself.  The cost keeps thousands of patients from access to a test that could potentially save their lives or allay their anxiety.

According to the ACLU website article on the case, “A gene patent holder has the right to prevent anyone from studying, testing or even looking at a gene. As a result, scientific research and genetic testing has been delayed, limited or even shut down due to concerns about gene patents.”

So this year for Christmas I am asking for more great work by the ACLU attorneys on this case, and for the court rulings to continue against Myriad and the holders of this patent.  The testing for our immediate family is already done, but it’s just wrong for a company to hold thousands of people hostage for testing of what belongs to these patients as much or more than it belongs to a corporation just does not pass the sniff test.  It just stinks.

Thanks for reading this medical blog.  Leave a comment and contribute to the discussion.

Then, as is Kay’s nature, a beautiful thought came to her.  She was getting a gift from two generous people who spent a bit of their day, and gave a part of their body in order that she could feel better.  This was an anonymous gift of love and caring from two ordinary people who did an extraordinary thing.  They went out of their way to donate blood.

Kay is a typical recipient of this generosity and heroic act.  Heroic you ask?  What makes this heroic? A hero is someone who does something most others don’t do to help someone else.  Blood donation fits this definition perfectly.

A minority of Americans are eligible to donate blood.  (<38% per the American Red Cross) .  I’ve been fortunate to be able to donate blood and do so regularly.  Kay has in the past, but because of her cancer is no longer eligible.  Still this is lots of eligible people, but only about 16 million units of blood are collected in the US annually.  5 million Americans annually receive blood products, some for acute life threatening conditions, but others like Kay in order to be able to walk up the stairs without struggling.

This holiday season is especially a time where blood banks run low on supply.  Take the time, be a hero, and give a Christmas or holiday gift to someone you may not know, but like Kay, may feel extremely blessed and grateful that you took the time and donated.

As an aside Kay has commented this weekend that she hadn’t really thought about it but the pounding of her pulse in her temples is now gone, she walks up the stairs without being out of breath, and is sleeping more soundly thanks to both of her generous donors.  Thanks to both of you, whoever you are, and thanks to the rest of you who donate regularly.  For the rest:  You can give a Christmas gift that’s free to give, and if not save a life, at least make a life better.  Just do it!

The list of conditions potentially covered by the VA as being Agent Orange related is pretty extensive.  A problem with evaluating these concerns is that many of the disorders that have been implicated as linked to Agent Orange exposure are common problems in people not exposed to Agent Orange.  I always tried to explain to patients that I had no way of knowing if their diabetes, ischemic heart disease, or other problems were caused by Agent Orange or not.  As most of you probably know Agent Orange was a mixture of chemicals used as a defoliant in Vietnam by the US military to destroy vegetation being used by the Viet Cong to hide.  I was in the Army, but fortunately my term of service was after the US withdrew from Vietnam.  In the office I’ve seen lots of veterans over the years who have been concerned about Agent Orange exposure and its relationship to various health care problems they have experienced.  The August 31, 2010 final regulations state that the VA has established a link between Agent Orange and Type 2 diabetes, coronary heart disease, and Parkinson’s disease.  Other disorders that have been linked to Agent Orange exposure include:

• Chronic Lymphocytic Lymphoma and other B Cell Leukemias.
• Acute and Subacute Peripheral Neuropathy.
• Hodgkin’s Disease and Non-Hodgkins Lymphoma.
• Multiple Myeloma.
• Amyloidosis.
• Numerous birth defects in women exposed to Agent Orange.

Veterans who have Agent Orange exposure and develop these disorders may be eligible to benefits and or compensation from the VA for these health problems.  Although it is easy for physicians, especially those younger physicians not familiar with the Vietnam Agent Orange fiasco to downplay these veterans concerns, it serves us well to at least be aware that these links have been established, and that the VA has in place a mechanism for evaluation and potential compensation and health benefits to veterans exposed to Agent Orange who develop these problems.