The Medical News Report # 57

October, 2016

Samuel J LaMonte, M.D., FACS

Subjects for October:

1. The Endocrine System--the Adrenal Gland-one of the “master glands”; the cortisone producer

2. Substance Abuse Series—Part 1--Alcoholism

3. Gastrointestinal Series—Part 14-Screening for colorectal polyps and cancer; Stool testing and Colonoscopy

4. Gynecological Cancer Series-Part 1-Ovarian Cancer—September was GYN Cancer Recognition Month

5. New Drug Pricing—Shameful!

Fall on Lake Keowee, South Carolina, not far from Sky Valley

IMPORTANT REMINDER!!!! PLEASE READ!!!

  I remind you that any medical information provided in these reports is just that…information only!! Not medical advice!! I am not your doctor, and decisions about your health require consultation with your trusted personal physicians and consultants.

  The information I provide you is to empower you with knowledge, and I have repeatedly asked you to be the team leader for your OWN healthcare concerns.  You should never act on anything you read in these reports. I have encouraged you to seek the advice of your physicians regarding health issues. Feel free to share this information with family and friends, but remind them about this being informational only. You must be proactive in our current medical environment.

   Don’t settle for a visit to your doctor without them giving you complete information about your illness, the options for treatment, instructions for care, possible side effects to look for, and plans for follow up. Be sure the prescriptions you take are accurate (pharmacies make mistakes) and always take your meds as prescribed. The more you know, the better your care will be, because your doctor will sense you are informed and expect more out of them. Always write down your questions before going for a visit.

  Now, on with the information!! Thanks!! Dr. Sam

1. The Endocrine System—the adrenal gland, cortisone, and Cushing’s disease

I have previously discussed the endocrine system in part, and for a quick review log on to:

www.themedicalnewsreport.com/31/32/33/34

  The adrenal glands are another part of the endocrine system that is crucial to life. You could call them the “master glands”. All endocrine glands secrete hormones, by definition.Since I have begun to discuss the urinary system, this is a perfect time to include the adrenal glands, because they sit right on top of the kidneys.

A. Anatomy

Below is a drawing of the endocrine system with the position and appearance of the adrenal glands. Note the location of these glands with the pancreas, another endocrine gland. 

There are 2 major parts of the adrenal gland—the outer adrenal cortex and the inner medulla.

B. Functions of the Adrenal glands:

   I. The adrenal cortexsecretes 3 major hormones:

1) Mineralocorticoids (aldosterone),conserve salt (sodium) in the body, and with that function regulates blood pressure. They work with two kidney hormones (renin and angiotensin) in blood pressure regulation.

2) Glucocorticoids (cortisone), which influences metabolism—by regulating blood glucose, burning protein and fat. The corticoids also respond to stress by acutely raising the levels in the blood necessary for the body to respond to that stress in addition to adrenalin secretion.

3) Gonadocorticoids, which assists in the regulation of sex hormones, such as estrogen and androgen(testosterone).  The adrenals actually secrete a small amount of androgen (but not estrogen), which is a consideration in prostate cancer (ridding the body of any testosterone influence if the prostate cancer is androgen- stimulated).

  II. The adrenal medullasecretes 2 hormones called catecholamines:

1) Epinephrine (adrenalin)

2) Norepinephrine (nor-adrenalin)

These 2 hormones are secreted in times of stress (fight and flight response).

  The adrenal gland is necessary for sustaining life due to regulating essential metabolic processes. These hormones would have to be given to a patient who has adrenal insufficiency.

C. Disorders of the Adrenal Glands

  1--The disorders of the adrenal gland are based on secretion of too much or too little of the adrenal chemicals.

  2--Too much secretion of cortisol can cause Cushing’s disease, which can lead to hypertension, osteoporosis, moon-face appearance from swelling, and other health issues.

The most common cause of this disorder is from taking medications (cortisone) to treat diseases such as rheumatoid arthritis, asthma, lupus, and other autoimmune diseases. Tumors of the pituitary or the adrenal(cancer or benign) can cause Cushing’s disease.

Ashley Judd had to take cortison

The media was horrible to Ashley because of the change in her appearance. Here is what she looks like in 2016 off steroids. Beautiful!!

  3--Too much secretion of aldosterone causes severe hypertension leading to cardiovascular and kidney disease.

  4--Too little secretion of these hormones is called adrenal insufficiency (Addison’s disease), which causes fatigue, weight loss, nausea, vomiting, and diarrhea. It is difficult to diagnose this disease, since the symptoms are so vague. Replacement hormones are necessary for recovery.

President Kennedy with a very thin face from Addison’s disease, and later on maintenance cortisone.

D. Tumors

  It is rare to have a primary tumor (malignant or benign)of the adrenal gland, but they dooccur causing excessive secretion of hormones and other adrenal chemicals. 70% of adrenal tumors are functioning (make excess hormones)tumors. 300-500 malignant tumors are diagnosed each year.

Another rare adrenal tumor called pheochromocytoma, can cause severe very resistant hypertension and should be thought of in such a case.

Adrenal tumors can be familial (genetic) in cause, and they can occur in other endocrine glands called multiple endocrine neoplasia syndrome in the thyroid (medullary carcinoma), parathyroids, pancreas, and around nerves (neuromas).Reference—Merck Manual

2. Substance Abuse Series-Part 1-Alcoholism

A. Scope

Alcoholism is an epidemic and the cause of destruction of every aspect of our society-family, friends, education, sports, and work. Alcoholism is a family disease with high rates of divorce, loss of jobs, domestic violence, alcoholism in their children, vehicle and domestic accidents, and psychosocial disarray.

  Alcohol consumption has continued to increase in the U.S. This has a great impact on future health service and alcohol treatment needs. I think the word “excess” is the mantra of our nation regardless of subject.

 Comparing 2001-2002 to 2012-1013, there has been an increase in drinking, especially episodes of heavy episodic drinking, frequency of consumption, and volume of intake with women leading men in the increases. This occurred in all race-ethnic minorities, however, it is magnified in blacks when it comes to episodic heavy drinking. The across-the-board hikes will increase challenges for the health consequences of alcohol and the number of Americans needing alcohol intervention and treatment. Reference: Drug Alcohol Dependency Journal 2015

  Physicians could do a much better job with screening and offering intervention for patients. Because this disorder is so common, treatment usually comes much later than it should.Primary care providers must ask patients about excessive use in daily drinkers. Patients will rarely ask for help. The family must reach out to get help for their loved ones with an intervention or at least bringing the problem to the alcoholic’s doctors.

 According to the American Association of Geriatric Psychiatry, by 2020, 4.4 million senior adults will need treatment for alcoholism, a 60% increase since 2000.  Today, Americans, as they age, tend to drink more, not less. The National Institute of Alcohol Abuse recommends no more than 3 drinks on anyone day. 

B. Definitions-abusers vs alcoholics

There are many more alcohol abusers than classic alcoholics that can’t stop drinking. Binge drinkers are at higher risk for true alcoholism, since by definition binging is abuse.

Alcoholism can be defined in many ways, but I like to differentiate abuse from alcoholism. When alcohol interferes with any aspect of a person’s life on a regular basis, I define that person as an alcoholic. Abusers, in my opinion, are not chemically dependent, rather they overdrink when they do drink but can stop. The gray zone is the functioning alcoholic, who gets drunk every night, goes to work and at least for some time, carries on a near normal life. Of course, the people around them would beg to differ. Blackouts are a suggestive sign that the person is an alcoholic. 

  The FDA defines moderate alcohol consumption as 1 drink per day for females and 2 drinks for males. This is equivalent to 12 oz. of beer, 5oz. of wine, and 1.5oz of liquor.

C. Statistics

16.3 million adults have alcohol use disorder, and 12-17% of those underage have this disorder. 88,000 deaths a year are alcohol related. 10% of children in the U.S. live with an alcoholic parent.

23% of underage people report drinking at least once a month and 14% report being binge drinkers.

4,300 deaths in our young Americans are occurring annually due to alcohol related incidents. Now, alcohol is being produced in powder form in various flavors. The AMA just came out with a plea for powered alcohol to be banned, making it illegal to produce and distribute. You know this will be a problem with underage youth.

D. Alcohol and Cancer

Alcohol is linked to 7 cancers: mouth, pharynx (throat), larynx, esophagus, pancreas, liver, and colorectal.

  Exercise, however, can reduce the excessive risk for cancer mortality if performed on a regular basis. This study did not define the amount of exercise or amount of alcohol.

Alcohol is broken down by the liver into a carcinogen (acetaldehyde), which can damage DNA in cells.

  While light to moderate consumption is beneficial to the heart because of its anti-oxidant effects, heavy consumption causes damage to the heart (cardiomyopathy) and blood vessels. Cardiomyopathy creates dilation of the heart (heart failure eventually), which increases the risk of arrhythmias, blood clots, and sudden death.

E. Alcohol and Neuro-Psychiatric issues

While light to moderate consumption may be associated with less dementia, heavy consumption (greater than 2.5 drinks per day) is associated with increase cognitive abnormalities, especially memory.

Nearly 1/3 of alcohol abusers have some form of mental illness.There is a correlation between substance abuse and mental disorders. Mental illness increases the risk of alcoholism by 20%. It may be more likely that alcohol may result in worsening of these illnesses including a higher risk of attempted and committing suicide. Many patients use alcohol as the drug of choice to “treat” their mental illness symptoms including simple stress. It is also associated with other risky behaviors such as smoking, thrill seeking, and reckless driving.

F. Effects on the brain

Although alcohol is classified as a depressant, the effects of alcohol (the “high”) are caused by increasing the levels of the chemical dopamine in the brain. There is some evidence that there is genetic influence on serotonin levels as well.

At high levels over time alcohol is toxic and interferes with the immune response and even the gut microbiome (gut bacteria), now known to influence many organ systems.

  Despite evidence that a patient’s physician can have a positive influence on alcohol issues, only 1 in 6 patients are screened for alcohol abuse in doctor’s visits.

F. Medical complications of alcoholism

 1--How alcohol causes damage to the organs!

Acetaldehyde, a metabolite (breakdown product of alcohol) is toxic to the system in many ways. It accumulates when the liver ceases to break down these byproducts. Nutritional deficiencies (especially Vitamin B-1- thiamine) cause metabolic changes that cause damage, especially to neural tissues.

2--Alcohol is one of the leading causes of liver damage, including alcoholic hepatitis, steatosis (fatty liver), cirrhosis (second most common cause), and liver cancer (30% is caused by alcohol), excessive bleeding, pancreatitis(second most common cause), cardiomyopathy, neuropathies,  trauma, mental health disorders, gastric ulcers, seizures, and ultimately death. Having treated many end-stage alcoholics, it is a horrible death.

3--Bleeding occurs from various sites. Dilated veins are caused by portal hypertension, which creates increased pressure in the liver veins, and this back pressure dilates veins in the lower esophagus, rectum, and makes the spleen swell. These dilated veins are called varices. These dilated veins can rupture with catastrophic consequences. Alcohol causes high blood pressure and increases the risk of cardiovascular events (hemorrhagic stroke and heart attack).

4--Link to heredity

Heredity plays a significant role in alcoholism accounting for about 50% of alcoholism with multiple genes involved. There are countless environmental influences including stress, work, relationships, family strife, sexual abuse, peer pressure, witnessing violence (PTSD), and drug accessibility.

If a person has alcoholism in their immediate families, it is important to not ignore this and be acutely aware of the risks of drinking, create strong family ties, avoid heavy drinkers, properly manage stress, monitor alcohol intake, and put a strict limit on the number of drinks consumed at any one time. If you can’t follow these guidelines, get help early. Denial is a terrible affliction for any addict.

G. Fetal Alcohol syndrome (fetal alcohol spectrum disorders)

  Maternal drinking during the first trimester can lead to this spectrum disorder including fetal alcohol syndrome, alcohol related neuro-cognitive and birth defects. This can include craniofacial anomalies, growth retardation, neurocognitive and learning disabilities, and behavioral abnormalities. Even mental retardation and seizures can occur. Early recognition is important to investigate these issues and treat them if possible. Reference- Healthline.com

H. Alcohol withdrawal--acute consequences—The DTs

Delirium Tremens (the DTs) will occur when a patient acutely withdraws from heavy continuous alcohol abuse. This is a medical emergency and must be treated in the hospital or alcohol center capable of treating the withdrawal symptoms.

Alcohol interferes with GABA (gamma amino-butyric acid) receptors which interfere with neurotransmission. In withdrawal, this creates loss of control of the normal neurotransmitters (norepinephrine, epinephrine, glutamine, and dopamine). This results in tremors, excitation, sweating, agitation, tachycardia (fast heart rate), hallucinations, elevated body temperature, hypertension,seizures, respiratory depression, cardiac arrhythmias, and death.

  9% of the U.S. population suffers from alcoholism. 50% of them have withdrawal symptoms needing treatment. There is a 5-10% lifetime risk of the DTs in chronic alcoholics. The current mortality rate is 5-15% even in adequate treatment facilities. Outside these centers, mortality rise to over 35%.

  Treatment of the DTs requires reversal of the above effects of the DTs with anticonvulsants, electrolyte balance with IV fluids, potassium, glucose, magnesium sulfate, vitamins (thiamine), benzodiazepines, beta blockers, and other supportive and selective drug therapies.

I. Treatment for chronicalcoholism--Naltrexone, Antabuse, Campral

  Treatment includes various abstinence programs (12 step and counseling) and medications.

Three drugs are FDA approved for alcohol craving and which can help abstinence, and decrease relapse rates:

1) Disulfiram (Antabuse) has long been used to prevent alcoholics from drinking (causes acute nausea if alcohol is consumed).

2)Naltrexone(Trexan), an opiate receptor antagonist, which can be beneficial in alcohol treatment. Alcohol craving tends to be curbed just as in opiate addiction. Both diseases affect the same brain centers.

3) Acamoprosate (Campral) also is effective by blocking certain brain chemical receptors (glutamate)

  Other medications used include SSRIs (antidepressants), anticonvulsants (Neurotin, Topamax, and Depacon).

References – WebMd, Alcohol Rehab programs, Mental Health Services, eMedicine.net

3.Gastrointestinal Series-Part 14--Screening for colorectal cancer (and premalignant polyps)

A. Background

  Screening is the best way to prevent and diagnose colon cancer early so that it can be cured.

  Colorectal cancer is the third most common cancer in men and women. If screening methods detect a colorectal cancer, there is a 90% chance of 5 year survival, and yet only 65% of men and women ages 50-75 undergo recommended screenings.

The USPSTF (U.S. Preventative Services Task Force) has recently revised its recommendations for screening and the ACS will soon publish their recommendations (I am on that committee currently finalizing our recommendations).

In this report, we will discuss the precursors of most colon cancers…colon polyps. Testing of stool samples and colonoscopy will also be outlined. Next month, I will report on colorectal cancer.

B. Definition of a colon polyp

Pedunculated (left slide)

Sessile (right slide)

Colon polyps are cells that abnormally grow from the lining cells of the colon. It is not known why they occur, except for certain hereditary syndromes that create multiple polyps (familial polyposis syndrome),some of which can become cancerous.

C.Risk Factors for colon polyps

There are people who have certain genetic mutations (KRAS, BRAF, p53, etc.) that are known to play a role in the genesis of some polyps.  Only 10% of all polyps become cancer. There are certain types of polyps that are more likely to become malignant (the flatter ones called sessile or serrated).

Even certain bacteria in the colon can predispose to developing polyps (S.bovis and E.faecalis), once again emphasizing the major role gut bacteria play in disease.

D.Classification of Polyps

  The classification of polyps (below left) includes inflammatory, hyperplastic, hamartomas, and a rare category all of which do not progress to cancer. Neoplastic (cancerous) polyps are the only category to worry about regarding the potential for cancer.

Neoplastic polyps--includes cancerous adenomas (only 10% of adenomas become cancer), adenocarcinoma (cancers can begin from a few cells without going through the transformation of a polyp), and carcinoid tumors (can occur in many sites including the colon and rectum) which develop from neuroendocrine cells that can secrete hormones and can be multiple.

Below is the complete classification of colon polyps on the left and symptoms of polyps on the right.

The symptoms of colon polyp do not occur until late when they are larger.

E. Protection against developing polyps and some cancers of the colon

  Aspirin (and other NSAIDs-i.e. Aleve and Ibuprofen), estrogen, folic acid, vitamin C and D all are to some degree protective against developing cancer. There are theories about where these agents selectively stop the progression of a polyp from benign to malignant.

Below is a schematic that proposes where they affect that progression. It also shows where these genetic mutations are thought to influence cancerogenesis (the creation of a cancer).

The above drawing shows the progression of a polyp to cancer formation

  --How NSAIDs work to prevent colon cancer

The COX-2 (cyclo-oxygenase) enzyme is involved with the formation of prostaglandins (an agent of inflammation). Aspirin and other NSAIDS block this COX-2 enzyme, which decreases inflammation and is thought to prevent polyp formation and thus the progression to cancer.

F. Types of polyps

Adenomas are also classified by the size and shape as well as pathologic type. Polyps, especially 9mm and larger, are the ones that create the greatest concern.

Adenomas are pedunculated (on a stalk) or flat-sessile(serrated). Those that are flat/sessile/serrated are the most likely to become cancer (15-30%). The pathology is classified as tubular, tubulovillous, and villous.

  Below are two diagrams depicting the percentage of adenomas (70%) that have the potential to become cancer and non-adenomas (30%), which do not progressto cancer.It is thought that it takes about 10 years for a small polyp to develop into a malignancy.

Many small polyps do not continue to grow and can be missed on screening.

G. Screening for colorectal cancer and premalignant polyps

Katie Couric lost herhusband to CRC, and has been a strong advocatefor screening.

Testing should begin at age 50 until age 75 for the average risk patient. After 75, the recommendations from the feds and the American Cancer Society leave it up to the individual and their doctor up to age 86. No organization recommends screening after 86.

The U.S. National Cancer Institute (NCI) estimates that 90% of colorectal cancer deaths can prevented with routine screening. Even though only 10% of polyps will become malignant, they must be removed for pathologic examination.

  In the U.S., only 65% agree to be screened when the evidence is so strong that screening is so valuable. Let’s face it….no one wants to have an invasive test, which creates fear, inconvenience, and concern about the prep.

  One study reported (Germany) that only 37% agreed to a colonoscopy. Of the 63% who refused colonoscopy, 97% agreed to a fecal test (15%) and a blood test (85%)-Septin-9, which are alternatives to colonoscopy. If these tests are positive, colonoscopy will still be necessary.

H. Screening tests

Comment—It is critical, from the age of 50, toinquire about the timing of being tested including their options. Doctors are so busy with treating acute and chronic illnesses, thatthey may forget to remind you to get screened. Be proactive!

By far colonoscopy is the most common test used to screen for cancer (63%), whereas only 10% use the fecal tests which are very effective as screening tests.

1. Fecal tests: (there are other tests but these are the most often used)

 a) FOBT-fecal occult blood test—tests for unseen blood in three different stool specimens on a yearly basis beginning at age 50 are very effective in detecting these lesions, however, compliance is a concern in getting patients to provide specimens on a yearly basis.

b) FIT-fecal immunochemical test (recommended yearly)--This test analyzes for any blood in the stool. This test is best served with 3 separate stool specimens collected at home using a kit and mailed into the lab. This test does not test for cancer, ratherfor unseen (occult) blood in the stool from any source. If it tests positive, colonoscopy will be recommended. 

c) DNA stool testing (Cologuard) (recommended every 3 years)--Cologuard tests for the amount of DNA coming from the cells of polyps and cancers in the stool specimens. It also checks for blood coming from polyps and cancers. The FDA approved this test in 2014. There is a kit that can be taken home to collect a stool specimen.  It is mailed to the company for analysis. No special preparation is needed prior to collecting a small sample. It is difficult to convince patients to collect specimens on a yearly basis, especially 3 separate specimens.

If the test is positive, a colonoscopy is recommended. The Cologard test can be offered instead of a colonoscopy if the patient refuses a routine endoscopic testing. This test finds about 70% of cancers (sensitivity) and when negative is accurate about 95% of the time (specificity). For best results, 3 separate specimens are recommended for the greatest chance of a positive test.

  d) A blood test (Septin9-DNA) to detect precancerous polyps and canceris in the investigational phase, but is promising (Epi-ProColon test). Improvements in the test are necessary before it will be approved.

Of course, any blood or fecal test, if positive, still will require a colonoscopy.

   e) Other sources of blood in the stool

  The origin of a positive test for blood in the stool could come from other sources, such as certain foods, certain medications including aspirin or NSAIDs (non-steroidal anti-inflammatory drugs), stomach or esophageal bleeding from ulcers, inflammatory bowel disease, hemorrhoids, and anal fissures. These issues limit the value of a fecal test.

2) CT-colonography

  A CT scan examines the colon without any invasive procedure and is just about as effective as the other tests in finding polyps and cancers, but has the drawback of still requiring a colonoscopy to remove polyps if seen on the CT.

The arrow points to a polyp in the colon (above photo). The CT-colonography is not currently being recommended as a screening test for the average risk patient as colonoscopy has a higher rate of detection.

3) Endoscopy (sigmoidoscopy and colonoscopy) 

  These are invasive tests requiring a tube that is inserted into the rectum to directly look at the all or part of the colon. Most gastroenterologists prefer to look at the entire colon (length-150 cm=60 inches) as a sigmoidoscopy only checks the rectosigmoid (length-60cm=23.6inches).

If a sigmoidoscopy is to be performed, it should include stool testing for blood (FOBT) or FIT. About half of cancers could be missed with a sigmoidoscopy alone. 

  Below is a drawing of the percentage of cancer in each portion of the colo-rectum). The greatest percentage of all colon cancers (60%) occurs in the descending and recto-sigmoid portion of the colon.  

Percentage of cancers in the colon

Sigmoidoscopy extent

Colonoscopy extent

Importance of the bowel prep

It is critical to have the colon completely clean before this test is performed, or it will be unsuccessful and need to be repeated. The quality of the bowel prep is critical, and there is intensive research in this area. Some of the latest implies a split prep as superior (half the prep the night before and half in the morning of the procedure).

One study stated that 25% of tests are inadequate because of ineffective bowel preps. Small polyps will be missed without an adequate prep (up to 42% of polyps missed).

  For a video of a colonoscopy: www.webmd.com/colorectal-cancer/video/colonoscopy

For an excellent discussion on preparing for a colonoscopy, click on: http://www.webmd.com/colorectal-cancer/colonoscopy-16695?pages=3

American Cancer Society Guidelines for colonoscopy starts at 50-75 years of age for those of average risk every 10 years. From ages 75-86, testing should be on a case-by-case basis. After age 86, it is no longer recommended. Fecal tests are better at detecting cancer, and endoscopy, etc. is better at detecting polyps.

  Keep in mind, if polyps are found on colonoscopy, a repeat test will be required within 3 years, depending on the type of polyps found and their pathology.

  For those with genetic mutations, family history of colon cancer, or certain colon diseases require earlier screening and more often.

Guidelines for testing and the timing

Note fecal tests should accompany sigmoidoscopy and the other tests except colonoscopy.

I. Removal or biopsy of polyps

 During colonoscopy, polyps will be removed if possible. Polyps on a stalk are easily removed with a snare wire with cauterization of the stump (drawing below). They are then analyzed to define whether it is benign, premalignant, or malignant. Flat polyps are more difficult to completely remove. Complications can occur with these invasive tests including perforation of the bowel leading to surgery.

  Below are drawings of removal of 2 types of polyps:

Pedunculated polyp

Flat or sessile polyp

J. Importance of Diet and prevention of Colon Cancer

There is probably no cancer more linked to our diet than colon cancer. A person can limit their chances of developing colon cancer with exercise, a diet high in fiber, less red meat and fat, maintaining a normal body weight, consuming calcium, taking an aspirin every day (85mg), getting screened for polyps with fecal tests (yearly) and or endoscopy (every 10 years).

Next month, I will discuss colorectal cancer.

4. Gynecologic Cancers-Part 1---Ovarian Cancer

The 6 major gynecologic cancers are uterine, cervical,

  The four major gynecological cancers are present in the fallopian tubes, ovary, vagina, and vulva. 93,280 women were diagnosed in 2015 and 30,440 women were predicted to die from these cancers in that year.

September was Gynecologic Cancer Awareness Month!

THIS DISCUSSION IS DEDICATED TO THE MEMORY OF Kay Hull, a resident of Sky Valley, Georgia. She was a beautiful human being, and loved by all. She was the quintessential fighter and eternal optimist.

Although these cancers do not have early symptoms, here is list of those that will eventually occur.

Over the next few months, I will address these cancers.

Reference –CDC—For information on GYN cancer, click on:

Before discussing ovarian cancers, it is appropriate to consider all ovarian cysts, because most cancers look like cysts, so most cysts must investigated.

Ovarian Cystsare very common, especially between the ages of 13-50. 98% are benign. They are usually fluid filled or solid. Larger cysts are more likely to cause pain, but are no more likely to be malignant than smaller ones. The solid cysts are more worrisome, and the only way to know if cancer is present requires a tissue diagnosis and a screening blood test called CA125.

There many different types of cysts including dermoids, polycystic cysts, endometriomas, and adenomas. A transvaginal ultrasound can discover them. Certain characteristics will define them, but if a cancer is suspected, an endoscopic exam including a biopsy is necessary.

B. Ovarian Cancer

Statistics and screening

To date, there are no specific early signs of ovarian cancer, and there has been no recommended screening tests for the general population for ovarian cancer. CA125 is recommended if there is a family history or the BRCA gene mutation.

  Screening guidelines may change after a recent study from the UK reported a 20% reduction in mortality in those who were screened versus no screening in a randomized study. Over 200,000 women ages 50-74 (without a prior history of ovarian cancer, family history, or a BRCA gene mutation) were tested with both theCA-125 blood test and a transvaginal ultrasound over 11 years. This study reported these combined tests led to an earlier diagnosis and a 20% reduction in mortality. Of course, the costs will prevent it from becoming routine in the U.S. any time soon.

Hopefully with more time and other studies, it will be clear that serial screening does save enough lives for women ages 50-74 and should be recommended for the general population (and covered by insurance).

  This study showed that testing the level of the CA 125 antigen over time will provide valuable information to find some of these cancers early.  Reference—Lancet, December, 2015

  A very recent report from the IOM (Institute of Medicine) stated that ovarian cancer should not be thought of as one disease rather it is a constellation of different cancers that involve the ovary. There are several subtypes that have distinct origins, risk factors, genetic mutations, biologic behaviors, and prognoses.

Gilda Radner

 Other celebrities who died of ovarian cancer include Madeline Kahn, Loretta Young, and Dinah Shore.

30% of women diagnosed with ovarian cancer can expect to live 5 years. The main reason for such a low survival rate is the disease has usually progressed to later stages (60% of the time) before being diagnosed.

Diagnosis requires a surgical biopsy, so finding a non-surgical method to diagnose these cancers earlier would be a life saver. Without definitive symptoms and a high index of suspicion, it has been difficult to diagnose these cancers before they have spread.

Facts

21,000 women are diagnosed annually and 14,000 die each year. Ovarian cancer accounts for 3% of all women’s cancers. Only 15% are diagnosed early. There is a 1 in 70 chance of a woman developing ovarian cancer during their lifetime. It is the most lethal of all gynecologic cancers. Although ovarian cancer can occur as early as 15 years of age, the average at diagnosis is 63 years of age.

Symptoms of ovarian cancer

  There are no early signs of ovarian cancer. Although these symptoms are non-specific, women in the age range of 50-74 must be aware of these symptoms if they persist over a few weeks.  Bloating, swelling of the abdomen, increasing waist size, pelvic or abdominal pain, weight gain, urinary urgency, or unusual vaginal bleeding can point to an ovarian tumor, whether malignant or not.

Lymph nodes via lymph vessels in green (above left) are where cancer spreads. On the right is an example of an ovarian cancer inside a cyst.

Spread of cancer

  Ovarian cancer can spread to the lymphatics, as shown in green, above. Spread to the liver and extension into the pelvis is not uncommon. Spread to lining of the abdomen (peritoneum) occurs as well.

  90% of ovarian cancers arise from the lining of the ovary (epithelial) with several subtypes:

1)serous 2) endometroid 3) clear cell 4) mucinous 5) undifferentiated.

The high grade serous cell cancers are the most common highly malignant cancers (2/3 of the cancers). It is thought that these cancers actually start at the end of the fallopian tubes and progress into the ovary.

  Less common histologic types include sex cord stromal, germ cell, primary peritoneal, and metastatic tumors. 

Staging of ovarian cancer

Stage 1—the cancer is confined to one or both ovaries.

Stage 2--extension to the pelvic region without spread

to the abdomen

  Stage 3--extension to the abdomen including the

peritoneum (lining of the abdomen)

Stage 4—distant spread to the liver, lungs, or lymph

nodes of the neck

  Below a drawing shows a cancer in the ovary (on the left). The right photo is an endoscopic view of an actual ovarian cancer.  The third demonstrates metastases to the peritoneum.

Small white spots are cancer

Risk Factors to develop Ovarian Cancer

  These factors increase the risk:

--BRCA 1 or 2 gene mutation (15-30% will develop ovarian cancer),

--a history of breast, ovary, or colon cancer,

--those on HRT (hormone replacement therapy in post-menopausal women-still some controversy),

--Age alone is actually a factor (50-74),

--Obesity, no children, a high fatty diet with high lipids (cholesterol), a history of endometriosis, no breast feeding, early periods, and late menopause all increase the risk,

--Talcum powder has been implicated in lawsuits (over a thousand). This month 2 suits in New Jersey were dismissed against Johnson and Johnson. There has never been a direct relationship proven, however, in losing 2 previous lawsuits for over $10 million, the talc suppliers to J&J put warning labels on the use of talc in the genital area in 2006, but J&J has never put warning labels on their products.

--Douching is a risk factor for ovarian cancer. A recent study determined there was almost a 2-fold increase. It also increases the risk of pelvic inflammatory disease (PID). It is now recommended not to douche routinely, as it is not necessary for good hygiene. Douche powders with added chemicals (especially phthalates) should not be used, however, plain water can be used if a woman needs to douche. Ref--J. Epidemiology, 2016

These factors decrease the risk:

 --Taking contraceptives or having a tubal ligation decreases the risk.

Testing for Ovarian Cancer

FDA Alert!!!

The FDA is warning women not to order screening tests marketed as a test for ovarian cancer. The test marketed by Abcodia as the ROCA test has not been proven effective in screening the general population. Do not order this test without discussing this with your doctor.

CA125

This blood test measures a protein (antigen) secreted by ovarian cancers, other cancers, and certain other medical conditions. The test is not accurate enough to be used as a general screening test, because non-cancerous conditions can raise the levels in the blood. 

CA-125 can be used to monitor an ovarian cancer or check for recurrence. It is also advisable if a woman is at high risk as mentioned above.

Transvaginal ultrasound (below)

In addition to the CA125 test, this ultrasound is the standard procedure to look for a suspected ovarian cancer. The ultrasound probe is placed in the vagina and gives excellent visualization of the pelvis structures.

This ultrasound shows cancer in the ovary.

If there is an abnormality on ultrasound, an MRI scan of the pelvis will be performed. An endoscopic examination and biopsy is then necessary.

MRI of pelvis showing cancer shows an ovarian cancer

Treatment for ovarian cancer limited to the ovary and immediate area without metastases

  Surgery--A radical hysterectomy and removal of the surrounding tissues is necessary to remove these aggressive tumors. Spread to the bladder or colon would prevent performing this radical approach. This requires a gynecological cancer expert preferably in a large cancer center.

  Surgical staging is frequently necessary including cytology studies of the peritoneum, multiple peritoneal biopsies, removal of the omentum (the apron of tissue that is attached to the bowel), pelvic lymph nodes and nodes along the aorta.

Laparoscopic surgery also may be helpful in investigating the extent of disease.

Cytoreductivesurgery,implies removingall visible cancer in the abdomen. The survival correlates with how much residual disease is left. Chemotherapeutic agents are used to hopefully get rid of the remainder of the disease.

Patients are then classified into three categories of metastatic disease:

1-microscopic (not visible) disease

2-macroscopic (visible) disease-disease present but limited to 2cm outside the pelvis

3-more than 2cm of tumor left after surgery or outside the peritoneal cavity (outside the abdomen). 

Interval debulkingis performed in those patients who did not have debulking of the tumor originally. 3 cycles of chemotherapy is then administered. 60% of patients are then able to undergo optimal surgical resection. 

Chemotherapy—most everyone will receive some type of chemo following surgery. The NCCN (National Comprehensive Cancer Network) recommends these agents (2015).

Treatment of metastatic ovarian cancer

Unfortunately, advanced or metastatic disease is present in 75% of the cases. There are many cancer centers performing clinical trials using several categories of therapy and combinations of drugs. Ovarian cancer commonly spreads to the endometrium, breast, colon, stomach, and the cervix. Later lung, liver, and brain can be targets.

The workup for metastatic disease (Stage IIIC and IV) includes a CT of the abdomen, pelvis, and lungs. 

  There are two schools of thought for treatment of metastatic disease—neoadjuvant chemotherapy and orcytoreductive surgery. If it is thought that the cancer can be removed or reduced to a small amount, cytoreductive surgery is preferred. The CA125 and carcinoembryonic antigen tests are used to further decide the course of treatment.

 Platinum/taxane combination therapy is recommended, however, there are alternate drugs that can be used as shown above.

  There are guidelines for continuing treatment for these patients, and it all depends on response to treatment. It is too complex to describe the algorithm followed by oncologists.

There is always hope

The bottom line is metastatic disease does not mean the cancer can’t be controlled or even cured. These advances have prolonged the lives of many ovarian cancer patients.  

Alternate Medical Treatments

Targeted therapy (Avastin) is another popular option, in that it attacks a hormone secreted by the tumor that stimulates blood vessels to grow. The process is known as angiogenesis inhibition. Blocking that hormone starves the tumor by decreasing the blood supply to the tumor.

Newer chemotherapy agents are used and immunotherapy is being tried by infusing medications that stimulate the patient’s own immune system.

Prognosis

Itcan be as high as 87% for the earliest cancers(Stage I-A) to 11% for Stage IV. If the patient has one of the 20% that has low malignant potential, these figures can be as high as 93% for Stage I-A and 30% for Stage IV.

A wonderful booklet for patients is available online:

www.nccn.org/patients/guidelines/ovarian/#100

Clinical trials are frequently the answer when standard treatments do not work. There is hope around every corner.

5. New information on drug price increases!!

  90% of drugs are considered generic and the percentage of the total drug cost is 28% of the total while the brand names account for 72% of the cost in our country.

  The 10% of drugs that are currently on patent  prevents other companies from making and selling the drug. The reason the cost is so high comes from the research and development  of new drugs (including failures). Our government has layers of regulations that prolong the process as well. The newer cancer drugs are an example of the enormous cost for patients(as much as $300,000 a year).

 The drug companies are protected by our own government who does not negotiate prices for Medicare patients. Most other countries can negotiate 20-30% discounts. This is clearly on our government’s back, and the drug companies are taking full advantage of it. Lobbyists have too much influence on Congress.

  Between the years of 2008-2015, most of our commonly used drugs have increased by 164%, while many of them have been on the market for years. And recently, even generics are rising rapidly (as much as 1000%).

  Before you accept a prescription from your doctor, ask him or her if it is a generic and is the cheapest option. Pharmacies are required to provide a genericopyion if there is one.  Many doctors have not paid much attention to drug costs. Make them!!!

  You read that the emergency injector of epinephrine for acute allergic reactions (EpiPen) has just jumped in cost by 400% (now over $600 for a two injector pack). Congress is after their CEO to reduce the price. The good news is that other companies have jumped on the band wagon and later this year should be selling them to the public. Greed is allowed by our own government….a bad aspect of capitalism.

  Brand name drug companies are paying big dollars to generic companies to delay the generic drug hitting the market as long as a year. This should be outlawed.

  We must stand up and insist our Congress change these regulations and negotiate prices, or at least allow drugs to be purchased out of our country. Canadian pharmacies are everywhere in Florida. Don’t believe the propaganda that these drugs are not the same. They are! We will see what our next president does about it.

  That does it for October! I hope you have a great fall and try to get up to where the leaves are changing. I will miss the leaves this year for the first time in many years.

  Next month, the subjects projected will be

1) ADHD-attention deficit hyperactive disorder

2) The crisis of opioid addiction and deaths—heroin crisis

3) Kidney infections

4) Colon cancer

  Stay healthy and well, my friends!! Dr. Sam

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