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More nuts and Bolts of Cancer

June 27th

This is dr kevin ryanmd mba facp and hematologist oncologist here, medical oncologist professor and retired colonel and cancer survivor and this is when tumor is the rumor and cancer is the answer. This show is Modeled after my non profit book of the same name available on the web site of the same name… you can find it on the web site and a lot more, interviews, films excerpts on the site and it is also available on amazon in all formats All shows are also on my blog off the web site  say name  and on www.w4cs  and in a few days iheart radio

Think of these next two shows as a mixture of nova and the wonderful world of disney- and the end of the nuts and bolts of Oncology –what you need to know to get started at really diggin in Following this is an intriguing two part series into the mind and eart of the Oncologist Why do they do it

Scope of Adult Oncology Practice

 

Our patient population involves treatment of those over 18, with two thirds of patients being over 65. The diagnosis of a primary (first time) cancer process is usually initiated by the primary care physician. Often some radiographic study (plain film, chest x-ray, mammogram, etc.) is ordered to evaluate some symptom (pain in bone, cough, lump in breast, etc.) or abnormality found such as (lesion, “hole” in bone, mass in lung, microscopic calcifications on mammogram) etc. Tissue diagnosis is then made: radiologists may use fluoroscopic device to biopsy bone or needle localization to biopsy breast masses; pulmonologists may use fiber optic bronchoscopy to look into and biopsy in the lung. Then the pathologist reads the biopsy sample as: cancer, not cancer, or suspicious  and perhaps gives a level or grade of severity depending on the cancer type and then calls the physician that sent him biopsy tissue to inform them of the diagnosis. Special stains of cell tumor associated products or fingerprinting of the traits of the material follow.

These can include Her 2 neu , Estrogen and progesterone testing in breast cancer and many more immunologic, hormonal, or genetic markers or assays of the actual biopsy material AND THAT NUMBER OF PERSONALITY TRAITS SO TO SPEAK, THAT FORENSIC FINGER PRINTING IS INCREASING EVERY DAY. Thus getting enough tissue is crucial and also being sure to get clear margins is often very important, if not at the biopsy phase, later. There is a phrase, intended to be a bit rough that I drill into the heads of all of my students. It nonetheless makes a crucial point and completes the mantra of the title of the book… “ Although  tumor is the rumor and cancer is the answer, tissue is the issue,  no meat no treat.” Getting to the meat of a diagnosis requires specific and adequate tissue.

This is not said to be cute, it is said to be memorable. Meat means you need to be sure you have enough of the

    • Right specimen from the right spot ( often assisted in the O. R. by various scopes and scanners.
    • The right labeling of orientation ( where exactly was it).
    • Submitted in the right way, fresh Vs fixed in the right amount and most importantly.
    • Submitted by the right people who not only know all of this but do so as a team.
  • Discuss your case before biopsy and every decision step of the way in conference as a team.When there is a team approach:

 

  • Your pain and suffering is guaranteed to go down.
  • Your odds of remission , its quality and durability and even the chance of cure go way up.
  • You recuperation at home is much better.
  • Your family is closer and more supportive.
  • Your insights into the less than optimal management of the most frightening diagnoses are greater making your ability to take and give in support groups.
  • You will live and love more. If you read MY book, I guarantee with YOU at the helm, your odds are best. This time YOU means an ACRONYM for
  • YOUR ONCOLOGY UNIVERSE- THEY all orbit around you the patient!

Treatment setting

 

Patients are treated primarily in the outpatient clinic setting. There has been a large evolution from inpatient to the outpatient (clinic) setting largely pushed by medical advances and health care reform that has decreased inpatient stays. New drugs are introduced specifically for the clinic setting more often than not.

There are also oncologist reimbursement issues. Outpatient care is often more lucrative with occasional uncommon inpatient episodes as a consequence of treatment: e.g. immediate complications such as allergic reaction to chemotherapy during infusion or chemotherapy leakage out of veins into tissues causing tissue damage (necrosis) leaving skin ulcers. There are also delayed (days-weeks) complications: infections, which can be life-threatening, diarrhea with subsequent dehydration, nausea and vomiting which very uncommonly can be relentless and delayed (weeks to months), and neurological complications as well as blood counts requiring replacement blood products.

 

 

BRIEF COMMENTS ON PREVENTION Prevention

 

 

This book has a focus on those individuals that engage cancer when tumor is the rumor or cancer is the answer. Thus, the massive and crucial field of prevention, cancer surveillance and screening is intentionally not addressed in any depth.IT IS MANY BOKS IN ITSELF Nonetheless, this book is also designed as a reference that can be read in logical order from start to finish as well as each section being able to stand up on its own, complete unto itself for quick referral as needed. This means that there is background information about the nature of cancer that better prepares you to fully participate in your care and exercise your autonomy. Thus some comments about prevention and screening are included WHAT I GIVE YOU IS ALL THE INSIDE SCCOP THAT YOU HAVE TO KNOW AND SEPARATE MYTH FROM REALITY

 

, there is also aN understandable fascination with and attraction to the science of Oncology as it represents conditions that broadly encompasses all aspects of the human condition, psychosocial, ethereal and of the flesh. It does so as a mimic of the normal tissues on the most fundamental genetic and macro or gross anatomic level .REMEMBER, cancer is a respecter of no one. Its understanding and treatment more deeply involves all aspects of medicine that perhaps any other field. More research dollars are poured into it than perhaps even cardiovascular disease. More drugs are rationally screened and designed for its treatment and management each year than any other disease and discoveries in its basic science routinely open more doors into the nature of what is life and  the tools which tell us so. Invader of anywhere, its story is one of the stories of the progress of modern medicine in all of its aspects, drug therapy, radiation treatment and surgery with all its combinations.

Thus, we know some of its causes, but not nearly enough and we know some of how to screen for it, but nowhere near well enough to profoundly impact the disease yet (with some exceptions). Thus, physicians are responsible to counsel all patients and family members regarding what we do know about diet, alcohol, sexual behavior, obesity, exercise, self-examination, over exposure to sunlight, pap smears, mammograms, fecal occult blood, and sigmoidoscopy. There are numerous sources the physician can refer the patient to such as the American Cancer Society, The American College of Surgeons, The National Cancer Institute and many more. A simple call to 1- 800 –4- Cancer will do it all.

There is no proof yet that the patient without symptoms or JUST high risk factors NOT FINDINGS benefits from routine scans of the body (whole body CAT, MRI, Ultrasound and such).  As we will discuss later, avoid reasoning by the anecdote wherein  some singular episode of something occurring is incorrectly taken to mean those results apply to you and thus you should be tested despite neither signs nor symptoms of proven high risk factors. Tests cost money and emotions . Many  tests done in this screening manner are neither sensitive nor specific (no false positives or false negatives) and worth the test cost as well being safe and effective as a screen. Another exception is the patient with a clear family pedigree of a number of cancers such as breast, various colon cancers and other rare genetically based syndromes as well as clinical presentations highly suggestive of an underlying malignancy. In addition it has been shown that in right age groups, mammogram and colonoscopy performed in patients with no known risks does make sense. This is also true of routine pap smear with exam and possibly true for routine blood testing in specific age groups for a specific protein related to prostate cancer with a well done physical exam for prostate cancer.

An overview of the top five areas of progress from the standpoint of diet, nutrition and weight management and cancer were recently the subject of a poll of the American Institute of Cancer Research. They concluded: 1. Excess body fat is a major cause of cancer 2. The scientific study of who survives and why is now fully underway in our research and university centers 3. Technology is making the evidence on causes much clearer and out of the realm of unsubstantiated claims. 4. A growing connection between diet and genes seems to be taking shape and 5. The same is true between diet and cancer links in general.

However, once a cancer is clinically established, it is not clear that any radical change in diet will have a direct impact on that cancer while not removing the possibility that it may impact development of a second cancer which had not yet taken hold (this is theoretic and nearly impossible to prove). Mega diet changes or frankly any dietary change radically different from those recommend by the National Institutes of Health has simply not yet been shown to be capable of stopping tumor growth, cause sustained remissions or cures and  prevented spread once tumor  is clinically  visible with routine tools such as physical exam and scans.

Cancer prevention means taking active steps intended to decrease an individual’s, or a whole population’s, risk of developing cancer. Most cancers have environmental issues as causes (other than aging) and lifestyle issues at their core meaning to some degree that they may be controllable. Thus, there is some reality to stating that certain aspects of cancer can be considered a preventable disease. For example, lung cancer does occur in people with no risk factors, directly or otherwise but they are a small minority. Thus, never smoking or being around it (second hand smoke) or being chronically exposed to significant levels of radiation or certain chemicals and a few other lesser factors are steps one can take to markedly diminish but not totally remove the risk of developing lung cancer.

Most experts say that about 30% of cancer risk can be diminished  by improving exercise, decreasing alcohol intake, not being obese, avoiding tobacco products , inadequate diet, avoidance of sexually transmitted disease  and to a modest degree severe air pollution as well as exposure to naturally occurring background radiation.

Dietary recommendations that may decrease cancer risk are (1) reducing energy dense highly processed foods and high corn syrup sugary drinks (2) increasing plant origin foods (3) Decreasing processed meat and high proportion of red meats (4) limit consumption of alcohol and salt and mold-risky cereals.

The data for each of these recommendations ranges from clear and strong to highly suggestive. Studies carefully looking at these observations show diminished colon cancer rates as well as pancreatic, stomach and breast cancer rates in populations of patients who markedly differ in these risk factors.

The notion that some form of medication readily available to all can limit our risk of all cancers is very attractive but unproven and often the source of great sorcery against unsuspecting patient’s souls and quackery. In certain circumstances there is some suggestive data. For example, aspirin has been found to reduce the risk of death from cancer overall but it is not a risk free drug. Teasing out how much of the effect is due to decreased cardiovascular disease is tough but the slight suggestion remains. Hormone blocking drugs tamoxifen or raloxifine can reduce the risk of developing breast cancer in high-risk women by 50%. Finasteride may decrease the risk of prostatic low grade cancers in men. Non steroidal anti inflammatory drugs celecoxib and a relative have shown in cases of familial adenomatosis polyposi  they may decrease risk of developing malignant polyps as well as possibly also in normal people ( with polyp tendency). However, this benefit comes at a price of increased cardiovascular risk.

Vitamins have not been found to be effective at preventing cancer, but low levels of Vitamin D is associated with increased risk-the nature of this observation is unclear. Beta carotene supplementation may actually minimally increase lung cancer risk and folic acid not only does not decrease colon polyps, it may increase them. Vitamin C definitely does not diminish cancer risk and it is dangerous, just as is Laetrile when given in large doses.

There are vaccines recently developed that prevent some infection by some viruses that are associated with cancer, and therapeutic vaccines are in development to boost our immune response against certain types of tumors. Two vaccines against certain strains of human pappiloma virus decrease later development of cervical cancer in infected patients that together cause 70% of cervical cancer. These vaccines also have a role in protection of males from later development of anal cancer in those chronically infected with HPV viruses.

 

BRIEF COMMENTS ON SCREENING Screening

 

Cancer screening involves efforts to detect cancer before it is noticeable in terms of signs or symptoms. Screens could be as simple as tests on stool for non-visible blood, to tests of the sputum, urine and multiple blood assays for proteins or blood markers associated with cancer and as well as various types of medical imaging.

Universal screening means applying the tests without disqualifiers to all people. Selective screening means limiting the test to specific people who for any number of reasons increase the odds of a true positive result and decrease the odds of a false negative result which is when we wrongly state all is well based on the test but in reality cancer is present.

One has to balance factors that affect test outcome before applying a screen in either case. There may be harms, clinically as well as psychologically from the test. There may be unnecessary radiation exposure or to dyes that might be allergic and so on. You only suggest a test with such risks when the risk of failure to screen a high risk patient is higher.

Sensitivity and specificity are covered a number of times in this book and it is well worth the time to have some basic grasp of the concepts. If a test is not sensitive, it will miss cancers when they are there. If it is not specific, it will wrongly claim it is there when it is not.

All tests can produce false positives and false negative with false positives being more commonly produced. Experts look at all of this and come up with the positive predictive value of a test which is a wise calculation based on collected data that a test claiming to show cancer in an individual has whatever power or accuracy to reveal people with true positive results.

If a cancer is rare, there is not much rationale for screening tests nor is it often helpful in young people as cancer is mostly found in people over the age of fifty. There are some exceptions but not many that stand up. There may be cultural differences where in the U.S. we screen for colon cancer far more than stomach cancer but in Japan stomach cancer screening is commonplace because the disease it is screening for is commonplace.

Positive screens may mean a lot more people undergoing invasive biopsies. If a test produces many false positives you may have bad outcomes if the biopsies hold some risk. The same holds true when screening for diseases for which treatment may not be suitable or available. If treatment is not available, then diagnosis of a fatal disease  may produce significant mental and emotional harms and must be weighed in an informed manner.

Even when treatment is available, finding cancer early may have no impact on outcome. The only thing then that screening does ( if positive) is make it appear the patient lived longer when in fact the added time was at discovery not at the end of their life. Furthermore, the only length of time increased is the patient knowing they had cancer for which there may or may not be effective therapy. This also IS true if the treatment result from screening is the same as without screening. All this is the notion of lead-time bias, where one knows the diagnosis earlier making it appear they lived longer.

A powerful screening program reduces years of potential life lost and disability adjusted lives (increases healthy lives). It truly catches diseases earlier where it made a difference doing so.

In our zeal as scientists, we can over diagnose. There are some cancers where no treatment may ever be necessary. One can see this in the elderly with slow growing cancers. Prostate cancers and hormonally receptive breast cancer in the elderly come to mind where perhaps no harm is done to watch and treat symptomatically in selected cases if and when therapy might be poorly tolerated and not affect quality of life or survival.

Remember, the patient is the one with the disease. Physicians and their patients should look at the logistical burdens the testing proposes and decide if it takes too much time for little reward.  If there is  or ARE cultural reasons, patients may not wish to participate. The law of patient autonomy must be respected.

Of course, there is the issue of the cost of screening. The US preventive task force recommendations ignored the issue of money. However, most good tests and studies that evaluated them include a cost effective analysis. Obviously, all else being equal, the less expensive test is the one supported. Such analyses do not just compare two tests to each other; they look at all the detailed costs associated with the test from development to interpretation and follow on biopsies. However, the costs to the individual are often hard to quantify and may not be done, such as time taken away from work.

The  U.S.  preventative Services Task Force ( USPSTF) recommends cervical cancer screening in women with a cervix and who are sexually active until age 65. They advise  annual stool blood testing and less frequent sigmoidoscopy or colonoscopy starting at age 50 until age 75 (every 5-1-5 to 10 years respectively) depending on which test was done. Routine screening for other cancers is not recommended. There is some disagreement regarding screening for prostate cancer. There is also some controversy by OR when to start mammograms in women with no family history. Presently the consensus is every two years for those 50-74 years of age. I DISAGREE Some researchers feel strongly that yearly mammography does more harm than good. As mentioned, Japan screens for gastric cancer and they use photofluorography to enhance sensitivity. (They use a dye to look for cell changes that assist the human eye.

Genetic testing for certain high risk patients is recommended as certain cancer syndromes are known to exist. The BRCA1 and BRCA2 genes are looked for in breast ovarian and pancreatic cancer. A number of other genetic tests are now suggested in certain GI and GU tumors from patients in families with multiple prior cancers. Patients showing as positive for these gene mutations then undergo more frequent other tests such as mammograms and various scopes and perhaps even preventative surgery or a trial at chemoprevention.

Again , the scope of this book is not screening. Far more detailed information can be found at the National Cancer Institute site for patients and at 1 800-4- CANCER

 

 

Cause

 

This is not a book centering on the cause of cancer, its prevention or survivorship. Those topics and perspectives are covered in droves. However, this work relates to the patient suspected of having cancer who is found in fact to have it and finds themselves awash in a sea of anxiety with almost no life buoys of knowledge to keep them and their families afloat until reaching a safer shore.

Entire careers have been devoted to the cause of cancer. For the perspective this book strives, it suffices to say that most cancers find their cause in an environmental basis. Large scale monozygotic ( identical) twin studies have shown that about (80%) of adult cancers are not primarily due to inheritance. You are not predestined to develop cancer with some notable exceptions of well-studied examples and family syndromes. Cancer is part of the aging process in many of us. For example, in time the majority of all elderly males will have often slow growing prostate cancer.

Malignant transformation and growth of a cancer is a genetic event but there must also be a breakdown, overwhelming or effective hiding from the patient’s immune surveillance system that accompanies the early malignant events allowing or facilitating their survival. Once again, this too is an acquired event and not something in-born  or pre programmed to happen (a common misconception). Of course, as we age, the constancy of spontaneous rising up of cells with malignant potential can eventually overload us as part of the normal process of aging. Nonetheless, it is not true that old age simply means you will definitely develop aggressive malignancy; it is more complex than that.

The cascade of events leading to the malignant transformation of cells and their subsequent ability or tendency to grow and spread is possibly the most active field of all clinical and basic cancer research. Your inherited genetic makeup does clearly have a role but it is not usually deterministic. There are unknown acquired genetic defects. Smoking is a major cause, high fat and low fiber diet, viruses such as is seen in AIDS and more rarely the virus of Mononucleosis and certainly alcohol and radiation exposure in excess increase risk.

The causes of cancer, while not a particular object of this SHOW, is nonetheless heavily related to our goal in that false beliefs in causes is often the battleground of numerous rumors where incorrect and damaging viewpoints and opinions can run amuck. For example, to some an honest answer regarding “why me” can seem flippant and almost irreverent because the response is; “why not”? Cancer is not a rare phenomenon and the longer you live the greater the odds. Of course, for some patients some strong singular risk factors are a familial relationship risk (in-born increased odds for a specific cancer). But to the largest extent  the answer is that it is a common disease whose risk increases with age and some lifestyle choice  factors and that there is no one single cause most of the time. For e.g. although cigarette smoking is a singular factor, the type of tobacco and the manner of the exposure is important and some (most) people escape development of both the small cell (solely related to tobacco products) and the more common non small cell cancers of the lung.

I will review the major categories of cause without delving into sophisticated data as that takes us off target too long and too far for too little reward.

It is usually impossible to prove exactly what caused a cancer in any individual, because most cancers have multiple possible causes. For example, if a person who uses tobacco heavily develops lung cancer, then it was very probably caused by the tobacco use. But since everyone has a small chance of developing lung cancer as a result of air pollution AND THAT DATA IS WEAK or radiation, there then is a tiny chance that the smoker’s lung cancer actually developed because of air pollution or radiation. In some cases we simply do not know why.

Cancers are primarily an environmental disease with 90-95% of cases attributed to environmental factors ( if we include age) and 5-10% due to genetics. Environmental means non-genetic causes. The common causative agents are tobacco  exposure 25%, obesity and diet 30%, types and chronic infections 30%, radiation meaning both non ionizing ( think suntans) and ionizing, (think radon), x rays 10%, lack of physical exercise and environmental pollutants. Stress is not clearly related to the cause of cancer in humans although this is chronically debated.

Lung cancers are highly related to tobacco smoking which has substances in it know as mutagens which cause DNA mutations which impact cell growth and increase the likelihood of metastasis. Mutagens that specifically cause cancer are known as carcinogens. Various carcinogens can cause various cancers, not just lung cancer such as cancers of the head and neck, bladder, esophagus, pancreas, larynx and kidney. Tobacco carcinogens are related to 90% of lung cancers and tobacco smoke contains over 50 carcinogens causing about a third of death in the developed world and one in five worldwide. Many mutagens are carcinogens but not all and not all carcinogens are mutagens. Alcohol is like that where about 10% of male cancers in Western Europe are related to alcohol whereas about 4 % of female cancers are.

Cancer related to one’s occupation may represent between 2–20% of all cases. Every year, at least 200,000 people die worldwide from cancer related to their workplace. Millions of workers run the risk of developing cancers such as lung cancer and mesothelioma from inhaling asbestos and leukemia from exposure to benzene in the workplace.

Diet, physical activity, obesity, and the overall adverse impact of obesity on immunity and the endocrine system play a cooperative role in many cancers. Poor diets low in balance of whole grains, fruits, physical activities and obesity are related to approximately 30–35% of cancer cases. In the United States, excess body weight is associated with the development of many types of cancer and is a factor in 14–20% of all cancer deaths. Physical inactivity is believed to contribute to cancer risk not only through its effect on body weight but also through negative effects on immune system function and through the endocrine system.

Diets that are low in vegetables, fruits and whole grains, and high in processed or red meats are linked with a number of cancers that were previously discussed. In addition, a high   salt diet is linked to stomach cancer. The frequent third world food contaminate afaltoxin is associated with liver cancer and Betel nut chewing with oral cancer. Thus, you will see cultural differences that shift when populations move into a new country of residence and do or do not continue their diet or origin culture.

We previously discussed infection in cancer with perhaps as many as 18% of cancers worldwide being related to infections. These infections were largely previously addressed but it is worthy to note both viruses and bacteria have been implicated. Viruses that can cause cancer are called oncoviruses. There are also viruses that cause forms of rare leukemia. In polluted third world rivers, parasites such as schistosoma haematobium and the liver fluke opisthorchis can cause can cause bladder cancer and cancer of the gall balder and liver ducts. This is not an all inclusive list but rather stresses the point that chronic irritation from infectious causes can lead to malignancy.

Radiation can cause all types of cancer after typically long periods of exposure and duration of radiation. Large dose have effects more immediately while most exposure has a long latency period between total lifetime dose and the development of malignancy. The young are most vulnerable to the bone narrow toxicities of radiation and the elderly to skin cancer due to lifetimes of exposure. The jury is in on tanning beds, skin is damaged and the risks for all types of cancer are increased. Children and adolescents are twice as likely to develop radiation-induced leukemia as adults are with radiation exposure before birth having ten times the effect. Ionizing radiation is not a particularly strong mutagen. Residential exposure to radon gas, for example, has similar cancer risks as second hand smoke.

Living near a nuclear power plant or power lines does not impact your cancer risk. The steps involved with chronic ionizing radiation in forming cancer are well known and are cumulative. Radiation is a more potent source of cancer when it is combined with other cancer-causing agents, such as radon gas exposure plus smoking tobacco.

The familial syndromes were briefly touched on previously. Members of these families can have increased risk of specific cancers such as breast, ovarian and colon as well as in general. Adding to the prior list are individuals who inherited a defective gene for repair of routine damage. The gene for controlling cell growth in these people is a mutation of gene p 53. They run the risk of a number of cancers, especially soft tissue and brain cancer. Mutations in the retinoblastoma gene defects  leads to the same named cancer in children. Those with well known genetic syndromes in general tend to have a generally increased risk of cancer, for example, Down’s syndrome where there are three copies of chromosome 21.

Some substances cause cancer primarily through their physical, rather than chemical, effects on cells. Asbestos exposure and other naturally occurring as well as industrial synthetic fibers can be inhalants leading to mesothelioma. Physical trauma as a cause of cancer has been debunked with the sole possible exception of chronically drinking scalding hot tea causing inflammatory defensive repairs similar to what is seen in people with chronic reflux of gastric contents . It is the repair, not the trauma that is the culprit.

Hormones were also previously addressed and the general mechanism is their stimulation of the growth of hormone dependent cells which may become uncontrolled and malignant.

Cancer is not a transmissible disease. It is not infectious with the rare possibility of transfer of cells during pregnancy and extremely rare transfer of cells during organ transplant, the most common of that rare event is melanoma

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