Genetic Testing Reveals Different Types of Prostate Cancer

The April edition of the journal Cancer contained a peer reviewed research paper by Weiner, Liu, Hakansson and associates describing their genetic analysis of 100,000 prostate tumor specimens. Their work revealed there are four distinctly different types of this malignancy, and they named them:

1. Luminal differentiated
2. Luminal proliferating
3. Basal immune
4. Basal neuroendocrine

These subtypes of prostate cancer seemed to behave differently and respond differently to treatments.  Some were more aggressive than others. Some responded better to chemotherapy and some to radiation therapy. 

The authors made it clear that their work was preliminary and that their observations about different levels of tumor aggressiveness and responsiveness to treatment were very preliminary. Well planned studies looking at these differences, their natural course and history and response to treatment will need to be undertaken before this breakthrough information can be relied on clinically. 

As technology advances, our ability to identify subtle differences in oncological diseases and then precisely apply therapy will hopefully make treatment more successful and efficient.

Patient Portals and Immediate Access to Test Results

I run a small concierge internal medicine practice caring for about 350 adult patients for the last 20 plus years. Prior to that I had a patient panel of 3,000 patients and a staff of 14 seeing patients in 15-minute sessions or less. As they got older and more complicated, my patients needed more time – not less.

As part of internal medicine care we draw blood (phlebotomize) and send it out to reference labs. We make no money from lab work, but we do carry the medical legal responsibility for interpreting it, reporting it and acting upon the results.  I have always called the lab work back to my patients the next day. In the pre pandemic era the labs returned the results by the next morning.  During the pandemic, and certainly post pandemic, the results routinely remain incomplete 48-72 hours after submission. When I call the results to my patients and explain what the labs mean, I am almost always asked to mail, fax, scan and email the results to the patient, several of their doctors and often a family member.

In recent months I am surprised to learn that many of the patients have established accounts with the reference labs and have the results long before I do.  By the time I call them they have looked up the meaning of the results that have an H next to them for “high” or an L next to them for “low”.  Before I can even begin to explain the results to them, they have fearfully zeroed in on “Dr. Google’s” writings and interpretations without any knowledge, perspective or experience in interpreting this data.  I am often concerned about changing trends in their “normal” results and it is difficult to get the patient to focus and hear what I am trying to explain because they are so concerned and so focused on the abnormal results.

Transparency is a wonderful thing in the right place and the right time, but I do not believe patients should have access to their results until the physician who ordered it has a chance to review it and report it. Yes, you can put a 48-hour time limit of keeping the data private before the patient can gain access to it but at least give us a chance to examine it, digest it and report it before we are pushed to explain away patients unjustified fears and concerns preventing them from hearing the important message.

In the April issue of JAMA Network, and summarized in the online journal Primary Care, 8,139 people participated in a survey regarding their thoughts on accessing test results once immediately available on an online patient portal. Although the overwhelming majority liked having this access, almost 8% admitted that the abnormal results caused a major increase in anxiety and worries. 

Life is complicated enough today without creating additional issues to worry about. Please give us health care professionals a chance to review and report the lab data before you get upset about data you have not been trained to interpret.

Bendectin in Utero A Risk Factor for Colorectal Cancer Early in Life

There has been a recent surge of colorectal cancer in men and women younger than 50 years old. The surge  has led to major revisions concerning the starting age to search for colorectal cancer with colonoscopies now being recommended in men and women 45 years of age instead of 50.  The reasons for the surge are being investigated. 

One theory involves the switch in sweet sugary drinks from real sugar to less expensive fructose corn syrup.  A publication in the March 10^th issue of JNCI Cancer Spectrum hypothesized another cause. In the 1960’s and 1970’s pregnant women in their first and second trimester were given a vitamin rich anti emetic called Bendectin. It was felt to be innocuous at the time containing Vitamin B6 and an antihistamine called doxylamine. It was voluntarily removed from the market in 1983 over concerns about heart defects and oral cleft palate development.

The current published study implicating Bendectin was  directed by Caitlin C. Murphy, PhD, M.P.H. of the University of Texas Health Science Center at Houston School of Public Health. Their researchers looked at 14,507 moms and 18,751 liveborn offspring who had the opportunity to use Bendectin for nausea. Almost 5% of the children were exposed to Bendectin in utero. For this group the incidence rate of colorectal cancer was 30.8  per 100,00 children compared to 10.1 per 100,00 in the non-exposed group.

The exact mechanism of action that Bendectin exposure increases the number of cases of colorectal cancer remains to be discovered.  The important fact is that mothers now in their 70’s and 80’s who took this product for nausea during their pregnancies need to tell their adult children about the exposure so they can inform their physicians and be appropriately screened. These adult children are now well into their childbearing years and no one has even looked at the question of whether or not their increased risk is genetically passed on to their children.

Screening for Colorectal Cancer with Fecal Immunochemical Tests

Preventive medicine is now directed by guidelines on who to screen, at what ages and how often.  Both the US Preventive Task Force (USPTF) and the American College of Gastroenterology have suggested we stop performing colonoscopies on patients 75 years or older whose previous colonoscopies have been normal. This is because the possibility of perforating the colon during the procedure rises dramatically in individuals 75 years of age and older. Also, the preparation for the procedure can create problems. In addition to these reasons, many patients diagnosed with colon cancer can be treated, remain alive and functional for far longer and well past their expected survival from all health issues.

I have a significant number of patients 75 years of age who have a family history of great longevity. They argue that they do not wish to deal with advanced colorectal cancer as they age. They recognize the risks of having a screening colonoscopy but don’t wish to assume the risk of undetected colorectal malignancy.

For some we can use Cologuard which genetically evaluates the cells from the colon sloughed when we move our bowels. Many insurers will not pay the approximate $500 for Cologuard in this age group. 

A recent article in the Journal of Clinical Gastroenterology and Hepatology touted the benefits of the much less expensive fecal globulin or FIT test.  This test examines the stool specimens of patients to detect human blood. It is far more accurate than previous “stool occult blood tests”. 

The study looked at 3,369 above average risk patients aged 50 – 74 with a previous adenomatous polyp detected or with a strong family history of colorectal cancer. They administered an annual stool FIT test and then followed it with a colonoscopy at two years.

Having a negative stool FIT test correlated well with having no cancer or precancerous lesions on colonoscopy. An annual FIT stool card may be a great way to screen those 75 years of age and older for colon cancer and to extend the period of time between colonoscopies in the younger age groups.  Ask your doctor for an annual FIT stool kit to screen for colon cancer.

Time to Screen for Lung Cancer

The United States Preventive Task Force (USPTF) for years has recommended that smokers and former smokers be screened annually with a low dose CT scan of the lungs. Despite this recommendation, experts believe less than 20% of the eligible patients are actually ever screened. In recent years they lowered the entry age and the number of cigarettes smoked to widen the surveillance. If you are 50 years old with a smoking history of at least 20 pack years (calculated as number of packs smoked per day x the number of years you smoked) you should be screened until age 80.

In a recent study published in the Annals of Internal Medicine, Iakovos Toumazis, PhD, of the University of Texas MD Anderson Cancer Center in Houston proposed an alternative risk model-based screening for lung cancer that may be much more cost effective and save more lives than the current USPTF recommendations. This model will be reviewed and may supplant current recommendations.

Leica Sequist, MD, MPH, and team at the Harvard Medical School and Massachusetts General Hospital of Boston have developed a screening tool using Artificial Intelligence with a program they developed named Sybil using one Chest CT scan. Their work was published in the Journal of Clinical Oncology and was able to look at pulmonary nodules and accurately predict which of those nodules, if any, had the ability to develop into a malignancy. Currently we follow these nodules with serial CT scans over a number of years to insure stability. One CT scan exposes you to the equivalent radiation of 200 chest x- rays so being able to scan only once and predict the future saves you from additional radiation exposure. While the researchers and scientists perfect the art and skill of finding lung cancer early, we still need our patients who are 50 years old or older with a smoking history of 20 pack years or more to step up and identify themselves so we can get them screened safely. With the use of electronic health records and the high-volume patient loads seen in primary care offices daily, this information is not always obtained and or captured in the record.

Cannabis Smoking Can Cause Emphysema

Giselle Revah, MD of the University of Ottawa Department of Radiology published a peer reviewed study in the journal of Radiology about the effects of smoking marijuana in patients enrolled in a lung cancer screening program. Marijuana is legal for recreational and medical use in Canada.

Since the legalization Dr. Revah, along with colleagues in internal medicine and family practice, have noticed an increased number of patients presenting at a younger age with emphysema and an increased number of non-trauma related cases of spontaneous pneumothorax (collapsed lung).

Her research team looked at the screening CT scans of marijuana smokers, non-smokers and cigarette smokers. When adjusted for age and sex, 93% of the cannabis smokers had emphysema compared to 67% of the cigarette smokers and < 5% of the non-smokers. Please keep in mind all the marijuana smokers were also cigarette smokers.

Dr. Revah found that those cigarette smokers with emphysema tended to be much older than the marijuana smokers with emphysema with many of the cannabis smokers with emphysema being younger than 50 years old. There was CT evidence in marijuana smokers of extensive airway inflammation, bronchial wall thickening, bronchiectasis and impacted mucous unable to be cleared easily. The study did not examine the CT lung scans of marijuana smokers who do not smoke cigarettes as well. That study is now in progress.

The message to patients and physicians seems clear. If you smoke cigarettes, then think about an alternative mechanism of obtaining the effects of cannabis than smoking. It seems that pot smoking plus tobacco may be synergistic leading to increased and earlier lung damage.

Misleading News on Colonoscopy for Colon Cancer Screening

I rarely take issue with research which is peer reviewed and published in prestigious medical journals but a study published in the New England Journal of Medicine regarding screening for colon cancer created more havoc and uncertainty about the worthiness of screening with a colonoscopy than is appropriate.

Michael Bretthaur, MD, PhD of the University of Oslo in Norway invited almost 85,000 adults aged 55-64 in Europe to participate in a screening colonoscopy or serve in a control group with no screening. Only 42% of those invited took the colonoscopy. Based on the large numbers in the study, the conclusion was that the procedure did little to reduce death from colon cancer over a 10-year period. This conclusion was noted by the international media and played up with the idea that maybe screening colonoscopy isn’t such a great tool? NBC and CBS nightly news covered it that way. CNN actually led with a misleading headline about it.

If you actually looked at just the data of those who had the procedure, it appears that colonoscopy reduced the incidence of colon cancer by 31 % and the risk of colon cancer related death by 50%. The message should have been “If you were screened with colonoscopy your chances of dying from colon cancer were reduced by at least 50%.”

There were problems with the study. The health care providers doing the colonoscopy were not as accomplished at finding polyps as the physicians who perform the study in the USA. The 10-year follow-up period of who developed colorectal cancer is considered too short a window for this particular disease which probably requires a 15-year observation window. The research team conducting the study will now be following the participants for another five years to correct this flaw. The numbers and conclusions are expected to change with the additional five years of data.

No sane person wants to prep for a colonoscopy and have the procedure. However. it is one of life’s necessary prevention evaluations. The media’s presentation of this study added great doubt to its efficacy. People will undoubtedly skip colonoscopy screening due to the way newspapers and TV news shows covered this study.

Colonoscopies save lives and by removing precancerous polyps with malignant potential save suffering too. I just had my colonoscopy. I hated every minute of the prep. The bowel cleansing preparation continued to upset my system for twelve hours post procedure. That said, it was worth every second of feeling uncomfortable to prevent a miserable disease.

New Blood Test Aids in Lung Cancer Screening

The US Preventive Screening Task Force updated its recommendations in 2021 for screening patients with  increased risk for lung cancer. Current guidelines call for providing a low radiation dose CT scan of the lungs annually for patients 50- 80 years old who have a smoking history of twenty pack years (calculated number of packages smoked per day x number of years smoking) and are still smoking or have quit within the last 15 years. These expanded criteria reduced the age to 50 from 55 and pack years from 30 to 20 years.  The recommendation is based on research showing that these criteria reduce deaths due to lung cancer by 20% as seen in the National Lung Screening Trial.

Despite this recommendation, many smokers who meet these criteria never get tested. Access to CT scans is one problem along with financial costs. For this reason, a group of researchers at MD Anderson Medical Center, led by Sam Hanash, MD, PhD, professor of clinical cancer prevention, developed a 4-panel blood test to screen for lung cancer. Their four test blood panel results were published in the Journal of Clinical Oncology on January 7, 2022.

The researchers then combined the results of the blood test with low dose CT scans of the chest and found that the accuracy of this method was far more sensitive than performing lung CT scans alone in the groups recommended for the procedure by the USPTF guidelines. Using the blood test and the low dose CT scan of the lungs, they found 9.2% more lung cancer cases for screening and reduced referrals for further evaluation by almost 14%

The blood test is still in the research phase and not available commercially for screening just yet. It will have to go through the full Food and Drug Administration (FDA) approval and evaluation process first.

The panel included tests for surfactant protein B, cancer antigen 125, CEA and cytokeratin-19 fragment. Currently the Ca125 test and CEA are available through commercial labs but there were no comments or recommendations from the authors or reviewers about whether clinicians should be using those two tests now with low dose lung CT scanning for screening.

Aspirin & Heart Disease Prevention Recommendations

In the 1950’s a research paper based on work done at a Veterans Administration Hospital found that men 45 years of age who took a daily aspirin tended to have fewer heart attacks and strokes. The VA patients were mostly male WWII and Korean War Veterans. That was the basis for most of the men in my Baby Boomer generation to take a daily aspirin.

Yes, we knew that aspirin gives us an increased risk of bleeding from our stomach and intestine. And we knew that if we hit our head while on aspirin the amount of bleeding on the brain would be much greater. It was a tradeoff – benefits versus risks.

Over the years the science has advanced to now distinguish those taking aspirin to prevent developing heart disease, cerebrovascular disease or primary prevention and those seeking to prevent an additional health event such as a second heart attack or stroke. To my knowledge there are no studies that examine what happens to someone in their 60a or 70s who has been taking an aspirin for 40 plus years daily and suddenly stops. It’s a question that should be answered before electively stopping daily aspirin.

Over the last few years researchers have hinted that the daily aspirin may protect against developing colorectal cancer and certain aggressive skin cancers. The downside to taking the aspirin has always been the bleeding risk. This data is now being questioned by the USPTF looking for more “evidence.”

The US Preventive Services Task Force was formed in 1984 with the encouragement of employers, private insurers selling managed health care plans and members of Congress to try and save money in healthcare. It is comprised of volunteer physicians and researchers who are supposed to match evidence with medical procedures to ensure that we are receiving high value procedures only.

In 1998 Congress mandated that they convene annually. Under their direction, recommendations were made to stop taking routine chest x rays on adult smokers because it didn’t save or prolong life and it took $200,000 of X Rays to save one life. They reversed their opinion decades later deciding that the math on that study wasn’t quite right and now recommend CT scans on smokers of a certain age and duration of tobacco use. I point this out to emphasize why I am not quite as excited today about their change in aspirin guidelines as the newspaper and media outlet stations seem to be.

I am a never smoker, frequently exercising adult with high blood pressure controlled with medication, high cholesterol controlled with medication and recently diagnosed non obstructive coronary artery disease. What does that mean? At age 45 my CT Scan of my coronary arteries showed almost no calcium in the walls. 26 years later there is enough Calcium seen to increase my risk of a cardiac event to > 10% over the next ten years. I took a nuclear stress test and ran at level 5 with no evidence of a blockage on EKG or films. The calcium in the walls of the arteries however indicates that cholesterol laden foam cells living in the walls of my coronary arteries and moving towards the lumen to rupture and cause a heart attack were thwarted and calcified preventing that heart attack or stroke. I am certainly not going to stop my aspirin.

My thin healthy friend who works out harder than I do told me he doesn’t have heart disease and is going to stop his baby aspirin. I asked him what about his three stents keeping several coronary arteries open? He told me he had heart disease before he got the stents but now he doesn’t. I suggested he talk to his internist or cardiologist prior to stopping the aspirin.

I may take a different path in starting adults on aspirin for cardiovascular and cerebrovascular event protection. I am certainly not going to withdraw aspirin from patients taking it for years unless they are high risk for falls and head trauma or bleeding. I suggest you ask your doctor before considering changing any of your medications.

Try an exercise by writing down all the prescription medicines and next to them list what condition you take them for. Once you have established that information, set up an appointment and talk about it with your physician. The decision-making is much more complicated than the USPTF and headline hungry media discussed and reported.

Some Health Issues Should Not Be Evaluated in the Office

I received a phone call from an elderly gentleman who was closer to ninety years of age than 80, was taking an aspirin and had just suffered a fall and hit his head. He did not know why or how he fell. He asked for an appointment the same day to “check me out.” 

My staff asked all the pertinent questions and immediately brought the information to me.  After reviewing it, I felt for his safety his best course of action was to immediately call 911 (or have us do it) and go to our local emergency department for evaluation. The patient takes daily aspirins to prevent a second heart attack or stroke.

The antiplatelet action of the aspirin, plus his age and the head trauma necessitate an immediate and thorough evaluation with imaging. I do not have an X Ray unit, CT Scan unit or MRI unit in my internal medicine office. If I bring this gentleman into my office, he must transport himself, wait until I have time later in the day and probably will then have to wait to be scheduled by an imaging facility for a non-contrast CT scan of the brain to make sure doesn’t have a bleed between his brain and skull or a bleed in the brain. The delay in evaluation can threaten his survival and recovery. 

The patient was quite angry at the suggestion – quoting my concierge practice contract that says we will bring you in for a visit same day for an acute condition. The non-stated content is that we will bring you in same day for a condition that is appropriate for evaluation in an office setting. The same can be said for someone calling with acute substernal chest pain which could be a heart attack or sudden inability to breathe.  Add in excessive bleeding that does not respond to compression or loss of consciousness as conditions that are best evaluated and treated in an emergency department. These are all conditions that require a call to EMS via 911 and an immediate evaluation in an Emergency Department where the equipment exists to quickly evaluate and treat these problems safely. 

The patient was worried about the wait in the ED and COVID-19 exposure. Both concerns are understandable despite little transmission of Covid recorded in ED visits or in patient hospitalizations.

This patient has emailed me twice now demanding a full refund of his membership fee due to violation of the contract. The reasoning and concern have been explained to him several times already. My concern is that his new onset short temper and grumpy demeanor are the result of the fall and head trauma which still has not been evaluated.

Patients need to know that there are times a health issue requires evaluation and treatment in an emergency department.  It has nothing to do with a contract.  It has everything to do with making the right clinical recommendation for the patient.