The Medical News Report

September, 2017, #68

Samuel J. La Monte, M.D., FACS

www.themedicalnewsreport.com

Subjects:

1. Brain tumors—status of Senator John McCain

2. Penicillin Allergies---Real or not?---relationship of antibiotic resistance and resistant infections

3.Eczema---diagnosis and treatment

4.Abdominal and Pelvic Vascular disease

5.Hematological System Series-Part 2-Red blood cell disease—Anemia and Polycythemia

6. Breast issues—an update--Breast MRI recommended for high risk patients; new guidelines for mammography for average risk women

7. Flu vaccine guidelines for 2017-18 just released by the CDC

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. Brain tumors-Diagnosis and treatment-- Senator John McCain and his options

Introduction

  Brain tumors are not very frequent compared to many cancers but always devastating (even if benign). There are far more benign brain tumors that malignant ones (53,200 non-malignant and 26,070 malignant) according to Mayo Clinic, but regardless of the type of tumor, it requires major surgery and potential disability, and in the case of malignant tumors the likelihood of mortality. That means just under 80,000 Americans will be diagnosed with a brain tumor in 2017 and one third will be malignant.

After leukemia, malignant tumors of the brain in children are the second most common cancers (4,820).Medulloblastomas are the most childhood type of brain cancer usually occurring before age 10. About 3 out of 4 will survive 5 years. A huge problem are learning and cognitive problems for their future.

  17,000 American adults with primary brain cancer will lose their battle this year.  Ref.--American Brain Tumor Association

Senator John McCain was recently diagnosed with a grade 4 glioblastoma (malignant glioma), an almost universally fatal cancer. The grades of tumor imply how malignant the cells are, and it doesn’t get any worse than a grade IV glioblastoma multiforme. That said, there is a lot of optimism for most patients diagnosed with a tumor of the brain. There are also spinal cord tumors, which I will exclude from this discussion.

MRI scan—glioblastoma

Frontal lobe tumor

This is an MRI (above) of a glioblastoma in the frontal lobe exactly where Senator McCain’s tumor was located. His tumor bled and may have been a blessing in disguise.Below is a specimen of brain demonstrating a glioblastoma multiforme in 2 locations in the brain.

Symptoms of a brain tumor

Regardless of the type of tumor, symptoms are based on the location of the tumor. The most common symptoms are headache, dizziness, balance issues, blurred or double vision, weakness of certain muscles, coordination difficulties, seizures, speech difficulty, cognitive issues, personality changes, weakness, and numbness.

How is a brain tumor diagnosed?

A. History and Physical Examination

As always the history and physical especially the neurological examination will usually point to a possible space-occupying lesion in the brain.  If a patient is having specific symptoms in an organ system, a careful analysis for a primary tumor somewhere in the body is necessary. Vision and hearing tests may be ordered. A spinal tap to check for genetic markers in the spinal fluid are used to determine certain mutations that may be linked to prognosis of certain brain cancers (i.e. MGMT gene mutation in glioblastomas).

B. Radiologic Examinations

  The brain CT scan and MRI with special dye and nuclear tests are the most common brain tests utilized. A PET scan is performed to inspect the entire body and may pick up primary tumors in other body organs as well as the brain. A PET scan with a radioactive injection in a vein is also used to determine if there is residual tumor present after treatment with chemo-radiation.  Benign tumors tend to have smooth well defined borders on scans, whereas cancers tend to have irregular edges and may be multiple particularly in the case of metastatic cancers.

  A chest X-ray, mammogram, scans of the kidney, bladder, and pelvis may be necessary to diagnose a tumor in these areas, as these are the organs most likely to metastasize to the brain.

C. Grading a tumor

Histopathology is necessary to grade a tumor (I-IV).Molecular testing of tumor tissue may be helpful grading and helping with prognosis of these tumors. Depending on the grade (I—least malignant; IV—most malignant), different treatments may be recommended. Lower grade tumors are more likely to be completely removed depending on the location and may have a better prognosis.  

Below are 2 examples of tumors in the brain on MRI scans:

D. Diagnosis--Brain biopsy vs craniotomy with attempted removal

  Certain cases may require a CT scan guided needle biopsy through a tiny hole in the skull, especially if the tumor is extensive and does not appear to be able to be removed. If the tumor appears to be potentially removable or needs to be reduced in size because of the location, a formal craniotomy may be performed.

Types of brain cells that have potential to become a tumor

It is important to review the function of certain key types of brain cells. This gives us the basis for knowing the cell origin of different types of brain tumors. The reason to understand this is treatment may be different for some of  these tumors.

Neurons and Supporting cells (neuroglia)

The brain is made up of neurons (nerves)and supporting cells calledneuroglial cells. Most tumors occur from these supporting cells not the nerves themselves.

Types of neuroglial cells and their function

The neuroglial cells are the glue and supporting structures for the neurons in the brain. There are 4 types of glial cells in the brain and 2 similar types for peripheral nerves (outside the brain). There are 4 brain glial cells:

1) Astrocytes--transports nutrients and holds neurons in place.

2) Oligodendrites--provides insulation (myelin sheath) to protect nerves.

3) Microglia--these cells are the macrophages of the brain that digest dead nerve cells and pathogens, and act as the main immune defense of the brain.

4)Ependymal cells--secretes cerebrospinal fluid from the lining of the ventricles in the brain.

Above in the drawing are 2 types of glial cells that support nerves outside the brain (peripheral nerves)

1) Schwann cells—form the sheath around nerves (myelin sheath) in nerves outside the brain (not the brain stem).

2) Satellite cells—these provide a covering of the ganglia portion (cell body) of a nerve outside the brain.

Think of nerves (10% by weight of the brain) as the circuits for transmitting information in the brain (80-100 billion neurons), supported by the supporting structures that provide nutrition and protection for the neurons (glial cells-make up 90% by weight of the brain).

Main types of glial brain tumors (gliomas)

The glial cells are the source of the majority of brain tumors a) astrocytomas b) ependymomas c) oligodendrogliomas d) brain stem gliomas

  The microglial cells do not appear to develop into primary brain tumors, rather they surround the outside ofastrocytomas in an attempt to create a defense against the cancer.

Gliomas make up 30% of all (children and adult) tumors of the brain and 80% of malignant tumors of the brain accounting for 75% of adult malignant tumors of the brain.

Grading of brain tumors (discussed above)

Astrocytomas (and other gliomas are graded from I-IV based on the degree of malignancy with the grade IV being the most malignant). Grade IV astrocytomasare calledglioblastomamultiformeandare the most common type of adult malignant brain tumor.

Childhood (0-19) brain cancers

Half of childhood brain tumors are astrocytomas. Less common tumors include ependymomas, medulloblastomas, diffuse pontine gliomas, and germ cell tumors.

Location of tumors--The main brain tumors (malignant and benign) include tumors inside the brain tissue and the lining (meninges). These include:

Benign tumors of the brain

Positions of most of the meningiomas (see above)

  A recent study in a clinical trial (200 patients) proved that stereotaxic radiotherapy (refined and precisely directed external radiation)is superior to conventional external radiotherapy for benign brain tumors and low grade cancerous tumors in children 4-25 years of age. There was less neurocognitive deficit in these young patients. This was reported in the JAMA Oncology.

Metastatic brain tumors

The most common primary tumors that metastasize to the brain are: Lung (48%), breast (15%), genitourinary-bladder and kidney (11%), osteosarcoma (10%), melanoma (9%), head and neck (6%), and neuroblastoma (5%), according to the Sloan-Kettering Cancer Institute.

  Approximately 100,000 Americans will be diagnosed this year with metastases to the brain. 20-40% with advanced cancer will eventually have spread to their brain. More than half of the patients will have more than one site involved. These numbers are rising because people are living with cancer longer. With progress in treatment modalities to control the growth of tumors prolonging life allows time for brain metastases to develop. Metastases tend to spread to organs that get the most blood (lungs, liver, and brain), and therefore if neurological symptoms develop, brain metastases must be suspected.

  Brain cancers rarely metastasize outside the brain.

  Most metastases occur in the cerebral hemispheres. The MRI with gadolinium contrast will define one or multiple masses—here is a breast metastases (left) and lung metastases (right):

Risk Factors for developing a primary brain tumor

Age (a child or older person), male sex, family history (5%), exposure to certain infections (Ebstein Barr virus, cytomegalovirus), electromagnetic fields, cell phones in children(controversial), white race, Northern European, seizures (controversial), nitrosamines in cured meats, smoking, cosmetics, and nerve agents from the Gulf War.

Treatment options

Treatment options vary with the tumor type and grade.

A. Surgery to remove and diagnose the type of tumor is always considered if it appears potentially resectable (removable). Surgical techniqueswill also depend on the position of the tumor in the brain. Tumors deep in the brain or in contact with the brain stem (most precarious position) are the most difficult to remove. Brainstem tumors can obstruct the flow of cerebrospinal fluid in the brain,interfere with the centers for respiration, and other vital life sustaining functions.

B. Radiation techniques are varied as well. IMRT (photon X-ray) external beam is a focused radiation sparing as much of the normal tissue. Proton radiation(not an X-ray but is an external beam) is even more focused and is being used more today especially in children.

C.Sterotaxic radiosurgery (cyber knife and the gamma knife are two types of equipment) is another modality used to direct highly focused beams to the tumor, usually a single dose treatment directly to the tumor, however, there are those sterotaxic techniques that use several doses of radiation (called fractionated doses).

The decision to use various types of treatment modalities depends on the stage of disease, tumor type, and genetic markers. The cancer center should provide you with enough information to make a rational decision. Doctors can be biased based on the equipment available in their institution, therefore, a second opinion is a good idea.

D.Chemotherapy

Chemotherapy is the other standard of care for most brain cancers. There are various options. Gliadel wafers (containing the chemo agent carmustine)can be placed directly in the tumor bed at the time of surgery.

  For glioblastomas the recommended therapy today is radiation with daily temozolomide (Temodar) doses followed by monthly treatments.

  A combination of 3 drugs is also currently being used: procarbazine(Matulane), lomustine(Gleostine), andvincristine(Vincasar). This combo lengthens the life of patients with grade III oligodendrogliomas.

E. Palliative care

Palliative treatments are also important to reduce symptoms and side effects of the standard treatment. Drugs such as corticosteroids and anti-seizure medication are commonly added to the standard treatment.

F. Targeted therapy

These medications target the tumor genes, proteins, and growth factors such as the anti-blood vessel growth proteins bevacizumab (Avastin). The field of targeted or biologic therapy is quickly expanding.

G.Alternating electric field therapy 

This is a device placed on the outside of the head that delivers electrical impulses. It apparently interferes with parts of a cell that are necessary for growth of a cancer cell. This has been used in glioblastoma and recurrent glioblastoma in a few cases.

H. Monitoring progress

MRIs every 2-3 months are used to monitor the progress of therapy. Side effects of these treatments may alter the course of therapy.

I.Clinical trials common for resistant and recurrent tumors

Because the results of standard treatments are not very successful, a large portion of these patients will be encouraged to enroll in clinical trials.

Unproven methods not in an approved major cancer center clinical trial waste perhaps the only time left for these patients. Clinical trials allow sharing of data to determine if these experimental treatments might be effective.

  The tumor characteristics must be considered when comparing new treatments. The age and histology of tumors strongly correlates with chemo-sensitivity (how well the tumor responds to chemo). These trials are small in number (14-30 patients) due to actual number of patients with glioblastoma multiforme.

  Florida clinical trials include these cities: Boca Raton, Gainesville, Tampa, and Orlando. In Georgia: trials are being carried out in Athens and multiple sites in Atlanta. For other states, search on centerwatch.com/clinical trials.

There is promise for the future as the molecular mechanisms and genetic mutations are being better understood.

J.Research continues for many potential treatments

Research experiments are ongoing using vaccines, checkpoint inhibitors, viral therapy, monoclonal antibodies, and other immunotherapies.

Survival Rates (5 year) and Prognostic factors

  The overall 5 year survival rate for brain cancers is 35%. It is rare for a patient with a glioblastoma to live 2 years, the average time from diagnosis to death is 11 months.

  When neurological symptoms begin, it is imperative to seek consultation.  

Medscape, Mayo Clinic, MD Anderson Cancer Center, American Brain Association, American Cancer Society

2. Penicillin Allergies----real or not?

A. General

About 10% of the population is said to be penicillin allergic and recent studies state only 10% of them are really allergic. A recent study at Parkland Hospital in Dallas, Texas reported 252 inpatients that stated they were penicillin allergic were skin tested, and 223 (88%) of these patients were skin test negative. In addition to skin testing, they were given 500mg of ampicillin with no reaction.  Mayo Clinic reported that 94% were not allergic in a similar but separate study.

B. How is drug allergy mediated?

  True penicillin allergy is mediated by the immunoglobulin IgE. A true anaphylactic reaction causes a spike in that immunoglobulin.

C. Consequences of not being able to take penicillins and cephalosporins

  If patients are supposedly allergic to penicillin, they are usually given more potent antibiotics, which lends itself to the epidemic of drug resistance.

  10% of those truly allergic to the penicillins are allergic to cephalosporins (i.e. Keflex), and therefore doctors are relunctant to prescribe either of these families of antibiotics.

Not having to avoid the penicillins and the cephalosporins allows the physician to stay away from potent antibiotics like vancomycin, clindamycin, carbepenems, and fluoroquinolones, which are responsible for a major part of the drug resistance phenomenon.

Erythromycin is the drug of choice if allergic to penicillin.

D. Consequences of potent antibiotics

   Patients that are labeled as penicillin allergic are more likely to develop infections fromClostridia difficile, methicillin resistant Staphyoloccocus aureus, vancomycin-resistant enterococcus infections and increased hospitalizations.  These infections are life-threatening and require even more serious antibiotics and longer hospitalizations.

E. Symptoms that may think patients are allergic to penicillin

Most of these patients have vague symptoms that attributed them to believe they were allergic, such as nausea, vomiting, or mild skin rashes (probably viral). 

  Of course, for those having clear cut severe allergic reactions, should wear a medic-alert bracelet or necklace.

  Once there is an entry in an electronic medical record stating a penicillin allergy, there will be no way a physician would prescribe this drug without a skin test.  In fact, it has been recommended that all pre-surgical patients that tell the hospital they are allergic to penicillin should be skin tested.

Many doctors right or wrong give prophylactic antibiotics, and if a patient states they are allergic to penicillin, stronger than necessary antibiotics may be prescribed. Skin testing is a good idea before eliminating both penicillin and cephalosporins.

Cephalosporins are frequently used as a prophylactic antibiotic, and if a patient has a negative skin test for penicillin, they can safely be given this antibiotic, according to a JAMA article (July, 2017). Discuss with your doctor!!

F. With a negative penicillin skin test, what should be done?

It is critical that the primary care physician have the records changed and instruct the usual admitting hospital  that the label of penicillin allergy be removed from all records. In one study, 65% of patients that were told that they, in fact, were not allergic, still had records at their primary care doctor’s office that had an allergic to penicillin sticker in their charts. BE SURE THIS INFORMATION MAKES IT BACK TO YOUR DOCTOR’S OFFICE if while in the hospital, this issue comes up.

  Resistance to antibiotics and superinfections (hospital based infections) are a real threat to all patients. It is critical that antibiotic allergies are investigated and if skin test negative, all records be changed. This is an important issue to bring up to the primary care physician for a plan.

Reference---American Academy of Allergy, asthma, and immunology.

3. Eczema (Atopic dermatitis)

Eczema, also called atopic dermatitis,is an itchy (pruritic) inflammatory rash that is characterized by dry skin (xerosis) with thickening of the skin from rubbing, and increased skin markings because of the skin thickening (lichenification). It is characterized by remissions and exacerbations.

30% of patients with eczema have or will develop asthma, urticaria (hives), food allergies, and allergic rhinitis (hay fever).

The word atopy refers to the genetic tendency to develop allergic diseases. They are a constellation of allergic manifestations inmany organs. All of these diseases have elevated IgE immunoglobulins, the classic elevated protein in the blood that occurs with allergic reactions especially those that arechronic. Patients who are atopic tend to have a heightened immune response to many allergens.  The eosinophil count (a special type of white blood cell) is elevated as well.Eczema appears to be increasing in frequency in the U.S. The vast majority of cases appear by age 5. A family history of allergies is common.

  Below shows a child with a facial allergic rash; the middle slide shows an allergic patch which is longer standing causing lichenification (very rough skin). The third slide shows an allergic rash on the back.

A well-known complication of chronic allergic skin rashes  is a chicken pox-like eruption caused by the herpes simplex virus (eczema herpeticum-left slide below) that can spread to all areas of eczema. It appears as tiny blisters (vesicles) and can occur after a smallpox vaccination (vaccinia). Another common complication is staphylococcal skin infections (right slide).

Reactions around the eyes, ears, and mouth are common. Contact allergic reaction to nickel and chromium (in paints), and cobalt are more common. Nickel is found in most metal like zippers, jewelry, etc.

There are several other skin diseases that must be ruled out including psoriasis, contact dermatitis, seborrheic dermatitis, scabies, and even a skin form of lymphoma.

10-12% of children and 0.9% of adults have eczema. Since this is a chronic disease, these children may carry their problem into adulthood or even can begin in adulthood. Patients with eczema also will experience other allergic issues such as asthma, food allergies, etc.

  Extremes of temperature tend to worsen the eczema. Hygiene plays a significant role.

Diagnosing eczema

  The diagnosis of eczema is a clinical one (requires a doctor seeing the patient and making the diagnosis visually). The diagnosis is not dependent on laboratory studies although an elevated IgE titer and eosinophilic count, etc. can be of value.

Treatment

 The mainstay of treatment is 1% topical steroid ointments twice a day. Treatment may also include warm compresses with petrolatum. Oils in bath water are helpful to lubricate the dry skin. After bathing, without drying off, it is recommended to apply petrolatum, aquafor, the newer productAtopiclair, or Mimyx topical treatments.

  Medications that may control the immune system include Tacrolimus, Pimecrolimus. Others include Omalizumab, Dupilomab, which should be reserved for resistant cases. These are extremely expensive.

Crisoborole was just FDA-approved which is a phosphodiesterase inhibitor which blocks inflammation.

  Benadryl (topical and oral) and hydrazine for itching is commonly used.

  Antibiotics are used if a Staph infection occurs, as this infection will flare eczema.

  Although there may be acute food allergens, most doctors do not withdraw specific foods from their diet unless there is an obvious clinical correlation.

  Probiotics are frequently recommended, however, evidence based research has not proven its value.

  A consultation with an allergist may be recommended especially if asthma, hay fever, orfood allergies develop.

Ref. Medscape

4. Abdominal and Pelvic Vascular Disease

  Atherosclerosis not only can clog coronary, cerebral, and carotid arteries, it can also block vessels in the abdomen, pelvis, and lower extremities. The major arteries in the abdomen can develop aneurysms, block vessels to the gut, the kidneys, and pelvic organs.

A. Abdominal Aortic aneurysms

  I have discussed aneurysms previously in 2 reports:

www.themedicalnewsreport.com #28

In quick review, aneurysms of the major abdominal arteries are created by weaknesses of the arterial wall creating a dilation of the vessel to the point of rupturing and imminent death from hemorrhage.

This drawing demonstrates a lower abdominal aortic aneurysm. A graft (inset) can be placed inside the aneurysm to restore normal blood flow without even removing the aneurysm. 

  Risk factors include smoking, male (over 60), genetic influence, and hypertension.

  Aneurysms develop over years and are silent until they rupture. Syncope, abdominal pain, nausea, vomiting, and shock can develop suddenly requiring immediate surgical intervention (emergency).

  Palpation of an abdominal pulsatile mass in the midline should alert the doctor to order tests to define this mass (ultrasound is the first test followed by CT scan to confirm).

Emergency surgery

Immediate surgical referral is indicated if there are any symptoms, especially if from hemorrhage into the abdomen causing swelling. Treatment must be performed before rupture if possible. A stent graft to bypass the aneurysm (inside the aneurysm), as seen in the drawing above is the standard of care.

  Once an aortic abdominal aneurysm ruptures, only 1 in 5 survive.

Medlineplus.gov

  B.Mesenteric Artery Thrombosis

What is the mesentery?

This term is used to name the investments of tissue that essentially hold the intestines in place. It carries the blood supply to the gut, and also the lymph vessels that drain the lymph. The plexus is connected to all lymph nodes in the mesentery.

 The drawing below shows the arterial supply from the mesentery to the colon with 2 major mesenteric artery branches:

When a vessel in the mesentery is blocked, this causes loss of blood supply to a part of the colon and causes acute pain (angina of the gut) in the abdomen and usually requires exploration of abdomen to find the problem including looking for a vascular blockage and or gangrenous bowel.

Symptoms include acute pain, bloating, diarrhea, nausea, vomiting, and fever. These symptoms occur in any acute abdominal syndrome.

Thrombosis(clotting) of a segment of this artery will cause ischemia, gangrene, and death of a portion of the small bowel. This portion of bowel will need to be resected (removed) and reconstructed. However, there are endoscopic procedures (including stents) to relieve the blockage that might be attempted in expert hands. Mesenteric thrombosis must be thought of with any acute abdominal pain. These patients are very sick and need immediate attention.

  These thromboses are usually arterial but can be venous as well.

Anatomy of the abdominal aorta

  There are major arteries to the organs of the abdomen, pelvis, and lower extremities. Below, the drawing (right) demonstrates arterial branches off the aorta to the liver, spleen, bowel, kidneys, pelvic organs, and lower legs.

       Abdominal branches of the aorta

  Atherosclerosis occurs over years, but just as in the coronary, carotid, or cerebral arteries, this occurs over decades until the lumen (inside of an artery) is stenosed (narrowed) with cholesterol plaque and eventually a clot forms over the rough surface of the plaque due to slow blood flow and can totally obstruct the vessel to a specific area of the gut.

  Imaging has advanced the diagnosis of this difficult crisis. Angiography, MRIs, Doppler flow studies, and ultrasounds can potentially define these blockages.

  Recovery is usually complete in most patients depending on the ability to diagnose and treat the patient quickly. Other cardiovascular issues may complicate recovery as well.

C. Renal Artery Stenosis

Patients with atherosclerosis are at risk for the same process that blocks the blood supply to one or both kidneys. Over time, this stenosis leads to difficult to treat hypertension.

  Risk factors include female, older age, other evidence of vascular disease, chronic kidney disease, diabetes, smoking, and elevated lipids. It is estimated that chronic renal failure is due to renal artery stenosis in 5-22% of cases.

  Kidney function tests, ultrasound (Doppler), and MRI scans all will define the status of the kidney and its major blood supply.

Treatment must start with the underlying disease, anticoagulants (aspirin) and may progress to angioplasty with stenting. This is recommended when the stenosis reaches 80% or less if the kidney function is diminishing (creatinine greater than 4).  Bypass surgery is performed less often. Removal of the kidney may be necessary.

Medicinenet.com

D. Pelvic Vascular Disease

Pelvic Congestion Syndrome is caused by poor drainage of the pelvic veins. Up to 15-20% of women have insufficient veins to drain the blood out of the pelvis leading to pelvic pain and congestion. Varicose veins can occur in the pelvis especially during pregnancy. I will discuss lower leg varicose veins at another time.

  The arteries to the pelvic organs rarely occlude, but erectile dysfunction from small vessel atherosclerosis is thought to play a significant role especially in diabetics, obese patients, and those with significant atherosclerosis. ED has been covered in previous reports:

www.themedicalnewsreport.com # 24

Next month, I will discuss peripheral artery disease of the lower extremities.

5. Hematological Series-Part 2-Anemia, Polycythemia-primary and secondary

A. Loss of, underproduction, or overproduction of red blood cells—the basics

Anemia

Blood cells are vital to our life, and when they malfunction, many diseases occur with major health consequences. Regardless of the cause, when there are not enough red cells (anemia), there is not enough hemoglobin, which is the protein that carries oxygen to the organs of the body. This causes fatigue, paleness, dizziness, shortness of breath, and even difficult or delayed healing.

Polycythemia

Overproduction of red cells can be caused by both benign and malignant causes.  Overproduction by the bone marrow stem cells cause polycythemia vera, and is part of what is called myeloproliferative neoplasms (malignant overproduction of red and white cells, and platelets). This will be discussed later in this report.

B. Anemia (iron deficiency, vitamin, aplastic, hemolytic, and anemia from chronic disease)

There are many types of anemia, however,iron deficiency anemia is the most common blood condition in the U.S. affecting 3.5 million Americans. Women tend to have more anemia than men, mainly because of menstruation, however, any significant bleeding (acute or chronic) will cause the loss of iron stores in the body and create anemia if the blood is not replaced by the bone marrow. Oral iron supplements are required to rebuild the blood. Older adults have anemia because of poor diet especially not taking in enough iron and vitamins, which are necessary to build red cells.

C. Three general causes of Anemia

In general, anemia is caused by three conditions-

1-bleeding, 2-decrease in production of red cells, 3- some type of destruction of red cells.The most common result is iron deficiency.

1-Blood loss most commonly occurs from gastrointestinal conditions (ulcers, hemorrhoids, etc.) and excessive menstruation or pregnancy. Aspirin and NSAIDs cause most of the bleeding in the stomach.

2-Faulty red cell production occurs from nutritional deficiencies of vitamins (folic acid and vitamin B-12), iron, and minerals. With gastric bypass surgery or chronic intestinal diseases, absorption of these minerals and vitamins can cause the problem from bypassing the stomach. Pernicious anemia requires a special factor in the stomach lining necessary to absorb vitamin B-12. Without it, injections of B-12 are necessary. B-12 shots have been given patients for decades as a placebo to boost energy, but its only value is for B-12 deficiency.

  Minerals including iron must supplement the diet when trying to restore the blood count to normal after surgery or other causes of blood loss. It usually takes 3-6 months of iron supplements to return the blood count back to normal range.

  A test called the reticulocyte count can be monitored to see if the blood is responding to treatment.

3-Destruction of red blood cells

There are several diseases that can destroy red blood cells. The symptoms include weakness, fatigue, and lethargy, because there is not enough blood to carry enough oxygen to the body. Common causes of destruction of red cells:

a) Hemolytic anemia

This type of anemia has many causes, but there are two main categories—hereditary and acquired.

        1- Hereditary causes of hemolytic anemia

--Sickle Cell Anemia

The most common cause is sickle cell anemia, which occurs in blacks and Hispanics. The red cell has a problem with the hemoglobin molecule not being able to carry enough oxygen in the red cells, and cause deformity of the cell, so called sickling. When it occurs acutely, this is called a sickle cell crisis, causing severe pain in the joints. Patients can carry the trait or have the actual disease. If two parents have the trait, they will have 1 in 4 chance of having a child with the disease, which is a very serious incurable disease. The abnormally shaped red cells can clot vessels and cause problems throughout the body decreasing the life expectancy to only 40-50 years (dying of stroke, infections, and chronic pain).

4-5 million people have the disease and over 43 million have the trait with the majority traced back to the sub-Saharan Africa and India resulting in 114,800 deaths worldwide in 2015. There are 100,000 Americans who have the disease.

There has been no new FDA approved medications for this disease in 20 years, but they just approved, L-glutamine oral powder (Endari) to reduce severe pain complications (sickle crisis-pain in the joints).

 Other hereditary causes include thalassemia, which also causes an abnormality in hemoglobin, which affects those from Asia, the Mediterranean, and Africa.

        2- Acquired causes of hemolytic anemia

--Aplastic anemia

   When the bone marrow is injured from medications, immune diseases (lupus, rheumatoid arthritis), chemo, radiation, viral infections (hepatitis, HIV, cytomegalovirus, etc.), or chemical exposures, the marrow quits making all blood cells including red and white cells, and platelets. This causes bleeding, anemia, and requires blood transfusions. Other treatments include bone marrow stimulants, bone marrow transplants, and immunosuppressant medications. This is a very serious illness leading to death unless treatments are successful.

Fanconi anemia is a rare cause of bone marrow failure, and 10% develop leukemia. Jimbo Fischer, coach of the FSU Seminole football team, has a son with this disease.

  The diagnosis of most of these anemias requires a bone marrow biopsy to detect abnormalities in the precursor red cells. The results will help dictate treatments.

D. Polycythemia—overproduction of red blood cells

This type of an elevated red blood cell count is caused by overproduction of the protein, erythropoietin, which is produced by the kidneys. The overriding cause is hypoxia (low oxygen levels in the blood). When less than normally oxygenated blood flows through the kidney, it stimulates erythropoietin, which signals the bone marrow to produce more red cells.

    Primary and secondary causes of polycythemia:

1. Primary Polycythemia Vera (PV)

A less common but serious condition is caused by overstimulation of bone marrow stem cells creating more red cells than normal. This is one of 3 conditions that are called myeloproliferative neoplasms. 1) Polycythemia Vera, 2) Thrombocythemia (elevated platelets), 3) Myelofibrosis (bone marrow stops making blood cells and is replaced with scarring), the condition Good Morning America’s Robin Roberts developed because of her breast cancer chemotherapy.

All three conditions develop mutations that affect the production of stem cells in the bone marrow. These conditions are responsible for various benign and malignant diseases (leukemia) which I will discuss in a November report on leukemia.

  Polycythemia Vera is classified as a malignant disease and, in fact, 7% develop acute leukemia. Polycythemia Vera is the most common of the three neoplasms (of the myeloproliferative neoplasms), and differs from secondary polycythemia in that there is red cell count elevation and an elevation of platelets (thrombocytosis) and white blood cells (leukocytosis). Because of this, abnormal clotting (thrombosis) is a real concern. The spleen and liver abnormally can producing blood cells causing enlargement of one or both organs (called extramedullary hematopoiesis). The most common gene mutation in PV is the Janus kinase 2 (JAK2).

Symptoms

  Many patients may not have symptoms but if they do, they may develop fatigue, weakness, bruising, headache, itching (pruritis),blurred vision, dizziness, numbness in the legs, abdominal pain (enlarged liver and spleen), fevers, and weight loss. Symptoms of gout (pain and swelling) in the big toe can occur. Skin flushing is common. PV usually has 3 different presentations:

a) Aymptomatic but present with another underlying disease (30% of the cases)

b) Thrombosis (clotting) occurs in 30% (heart attack, stroke, etc)

c) Signs and symptoms of PV in 30-40% of cases.

Treatment

Because polycythemia Vera and the other myeloproliferative neoplasms are chronic in nature, the goal of treatment is prevention of clotting and careful monitoring for the development of other complications such as acute myeloid leukemia.

The goals of treatment are similar for both secondary polycythemia and Polycythemia Vera: aspirin, Persantine, and hydroxyurea are recommended to prevent clotting issues, and phlebotomy (removing a pint of blood) to keep the hematocrit below 45 for men and 42 for women.

Chemotherapy is used to prevent intractable pruritis (itching), ocular migraine, and the abnormal formation of blood cells in the spleen and liver that can occur in these neoplasms.

Targeted therapy

Since these neoplasms cause bone marrow proliferation of blood cells that can lead to leukemia, the new targeted therapies are being used to destroy those stem cells. 

Ruxolitinib (Jakafi) is used to inhibit JAK2 gene mutation, reduce the size of the spleen, to prevent rupture. This is used if the first line treatment (hydroxurea) stops working or is not tolerated. Splenectomy may be necessary if the spleen does not respond or is too large to run the risk of an acute rupture.The drug, Jakafi, has kept patients in remission 5 times longer than hydroxyurea.

Interferon is the only medication that can specifically target the abnormal cells being produced in the bone marrow (and also in the liver and spleen) and relieve symptoms of this disease. Complete remission occurs in about 18% of patients.    

  The only curative therapy is stem cell transplantation for all the myeloproliferative neoplasms including Polycythemia Vera.

Life Expectancy

Most patients are diagnosed by the age of 60 and usually live 20 years. For those who develop serious complications of this disease, life can be cut short by many years.

NEJM, 2017—Myeloproliferative neoplasms

    2. Secondary polycythemia

The most common cause is emphysema (chronic obstructive pulmonary disease), a very common debilitating lung disease.

Other causes include other conditions including congestive heart failure, sleep apnea, and pulmonary hypertension. Stress (Gaisbock’s disease), renal artery stenosis, and kidney transplants can also cause polycythemia. People living in higher altitudes have thicker blood as well to compensate for lower ambient oxygen levels. Even heavy smokers can develop polycythemia.

  There are rare tumors that can secrete the kidney protein erythropoietin including kidney, adrenal, and liver cancers, and uterine tumors. Rarely cysts in the kidney can cause the problem. Interestingly, professional athletes blood dope with injectable erythropoietin (EPO), to increase their oxygen carrying capability, especially cyclists (Lance Armstrong).

  Dehydration for any reason can cause a relative polycythemia until the patient is rehydrated.    

Symptoms

They include weakness, fatigue, headache, bruising, joint pain, dizziness, itching, and abdominal pain.  The problem with having too much blood is that thick blood clots easier causing thrombosis of vessels in multiple parts of the body (stroke, heart attack, etc.). Because of high turnover of red cells, there are increases in byproducts filtered through the kidneys and may lead to damage, kidney stones, and gout. 

Diagnosis

The CBC will report an elevation of the hemoglobin, hematocrit, red cell concentration (MCHC). The hemoglobin (>14 gms/dl), Hematocrit (men >50, women > 45) is above these ranges.

Treatment

The treatment is aimed at treating the underlying the disease, since these types of polycythemia are secondary to those diseases. Stopping smoking is recommended.

  Patients can have a phlebotomy to remove a pint of blood on a regular basis if necessary. Patients often report feeling much better when the excess blood is removed. The intent is to keep the Hematocrit below 45 in men and 42 in women.

  Aspirin, Persantineand hydroxyurea aremedications  recommended in cases when blood clotting is of great concern, especially in patients over 70 years of age.

Mayo Clinic, Medpage, emedicine.com

Next month, I will discuss the white blood cells and their diseases.

6. Breast issues-- updates

Breast MRI recommended for high risk patients;

   New Breast Screening guidelines for average risk women

A. Breast MRIs

Breast cancer screening is a hot topic, and the American Cancer Society recently published their recommendations (I was on the committee that researched and published the findings) for women with routine risks. Our committee will be addressing high risk women this year as well.

Breast MRIs are now being recommended annually for high risk patients starting at age 30. The National Comprehensive Cancer Network has guidelines for this group, which can be obtained online. Patients who are at higher risk (greater than 20% lifetime risk) include those with a strong family history, especially first degree relatives with breast cancer, BRCA and other gene mutations (PTEN, TP53), those with chest radiation between ages 10 and 30, and those who have had previous breast cancers. A relative risk is significant breast density, although not included in the high risk group.

Breast MRI can detect 90% of breast cancers while mammograms can only detect 40% as reported by the chief investigator of the research discussed here from the University of Pittsburgh, Department of Radiology. It should be noted that some breast cancers are detected better with mammography (low grade ductal carcinoma) and therefore both tests are recommended in the high risk women. MRI can detect invasive ductal carcinoma better.

Ultrasound is frequently recommended in addition to digital mammography for women with dense breasts and is also recommended when MRI is not available or unable to have the test.

  MRIs have proven to reduce the number of late stage breast cancers and metastases to lymph nodes. In this study, the average tumor diagnosed was 0.9cm (1/3 inch).

  For those with an intermediate risk (15-20%), this study stated there was insufficient evidence to recommend annual MRIs.

  The excessive cost is a real consideration when recommending MRI for a national group, and even though I am reporting this information, it is always the responsibility of the patient and doctors to decide what screening techniques are recommended.

  Our American Cancer Society screening guidelines committee will have their guidelines out by the end of the year. Medpage Today, March 22, 2017

B. New screening guidelines for average risk women for mammography from the American College of OB-GYN

The earlier mammograms are started the higher number of false positives, unnecessary biopsies, and even unnecessary treatments, but the statisticians can show a number of lives saved. It has become a big debate about the risk/benefits of earlier testing. Physicians are just as confused as patients because a new set of guidelines from various medical associations comes out at least once a year changing the recommendations. Here is the latest:

7. Flu Vaccination Guidelines for 2017-18 just released by the CDC

  It is time to start thinking about getting a flu shot by the end of October, so be sure you and your family does not procrastinate. “Getter Done”!

This completes the September Medical News Report.

Next month, more great subjects planned:

1. Obstructive sleep apnea update

2. The high cost of prescription medications

3. White blood cell and platelet disorders

4. Longer waits for doctor’s appointments

5. An opioid crisis update--? a vaccine against heroin; misuse of certain non-opioid drugs for pain

6. Peripheral artery disease of the lower extremities (PAD)