End-stage Liver Disease (ESLD)

 

Chronic liver failure, also called end-stage liver disease, progresses over months, years, or decades. Most often, chronic liver failure is the result of cirrhosis, a condition in which scar tissue replaces healthy liver tissue until the liver cannot function adequately. Patients with abnormal liver function who develop ascites, variceal hemorrhage, hepatic encephalopathy, or renal impairment are considered to have end-stage liver disease (ESLD).

While liver transplantation is a viable treatment option for ESLD, with increasing waiting times for organ transplantation, nearly 17% of patients on the transplant wait list die annually; others are not candidates for a liver transplant. Patients with ESLD have a constellation of symptoms and disease-related complications that affect survival and health-related quality of life.

What causes cirrhosis?

When a substance or disease attacks and damages the liver, liver cells are killed and scar tissue is formed. This scarring process is called fibrosis (pronounced "fi-bro-sis"), and it happens little by little over many years. When the whole liver is scarred, it shrinks and gets hard. This is called cirrhosis, and usually this damage cannot be undone.

Any illness that affects the liver over a long period of time may lead to fibrosis and, eventually cirrhosis. Some common causes are heavy drinking, viruses, a buildup of fat in the liver, inherited diseases, toxic effects from drugs and autoimmune diseases. These are more fully explored in the next section.

Cirrhosis has numerous causes. In the United States, heavy alcohol consumption and chronic hepatitis C have been the most common causes of cirrhosis. Obesity is becoming a common cause of cirrhosis, either as the sole cause or in combination with alcohol, hepatitis C, or both. Many people with cirrhosis have more than one cause of liver damage. 

Cirrhosis is not caused by trauma to the liver or other acute, or short-term, causes of damage. Usually years of chronic injury are required to cause cirrhosis. 

Common Causes of Cirrhosis

Alcohol-related liver disease.Most people who consume alcohol do not suffer damage to the liver. But heavy alcohol use over several years can cause chronic injury to the liver. The amount of alcohol it takes to damage the liver varies greatly from person to person. For women, consuming two to three drinks-including beer and wine-per day and for men, three to four drinks per day, can lead to liver damage and cirrhosis. In the past, alcohol-related cirrhosis led to more deaths than cirrhosis due to any other cause. Deaths caused by obesity-related cirrhosis are increasing.

Chronic hepatitis C

The hepatitis C virus is a liver infection that is spread by contact with an infected person's blood. Chronic hepatitis C causes inflammation and damage to the liver over time that can lead to cirrhosis.

Chronic hepatitis B and D

The hepatitis B virus is a liver infection that is spread by contact with an infected person's blood, semen, or other body fluid. Hepatitis B, like hepatitis C, causes liver inflammation and injury that can lead to cirrhosis. The hepatitis B vaccine is given to all infants and many adults to prevent the virus. Hepatitis D is another virus that infects the liver and can lead to cirrhosis, but it occurs only in people who already have hepatitis B.

Nonalcoholic fatty liver disease (NAFLD)In NAFLD, fat builds up in the liver and eventually causes cirrhosis. This increasingly common liver disease is associated with obesity, diabetes, protein malnutrition, coronary artery disease, and corticosteroid medications.

Autoimmune hepatitisThis form of hepatitis is caused by the body's immune system attacking liver cells and causing inflammation, damage, and eventually cirrhosis. Researchers believe genetic factors may make some people more prone to autoimmune diseases. About 70 percent of those with autoimmune hepatitis are female.

Diseases that damage or destroy bile ducts

Several diseases can damage or destroy the ducts that carry bile from the liver, causing bile to back up in the liver and leading to cirrhosis. In adults, the most common condition in this category is primary biliary cirrhosis, a disease in which the bile ducts become inflamed and damaged and, ultimately, disappear. Secondary biliary cirrhosis can happen if the ducts are mistakenly tied off or injured during gallbladder surgery. Primary sclerosing cholangitis is another condition that causes damage and scarring of bile ducts. In infants, damaged bile ducts are commonly caused by Alagille syndrome or biliary atresia, conditions in which the ducts are absent or injured.

Inherited diseases

Cystic fibrosis, alpha-1 antitrypsin deficiency, hemochromatosis, Wilson disease, galactosemia, and glycogen storage diseases are inherited diseases that interfere with how the liver produces, processes, and stores enzymes, proteins, metals, and other substances the body needs to function properly. Cirrhosis can result from these conditions.

Drugs, toxins, and infections

Other causes of cirrhosis include drug reactions, prolonged exposure to toxic chemicals, parasitic infections, and repeated bouts of heart failure with liver congestion.

 

Complications of Cirrhosis

Because the liver becomes lumpy and stiff in cirrhosis, blood cannot flow through it easily, so pressure builds up in the vein that brings blood to the liver. This vein is called the portal vein. When pressure is high in the portal vein, the condition is called portal hypertension. In order to relieve this pressure, the blood passes through other veins. Some of these veins, called varices, can be found in the pipe that carries food from your mouth to your stomach (the esophagus) or in your stomach itself.

When a person has cirrhosis, the high pressure in the portal vein backs up into another organ called the spleen, which becomes enlarged and destroys an excessive number of platelets, the blood particles that help with blood clotting.

 

With cirrhosis, entrance of blood to the liver is blocked and substances such as ammonia that would normally be cleaned by the liver, escape into the general circulation.

Aside from the problems with liver blood flow, when cirrhosis is advanced there aren't enough healthy worker cells to get all the work done, so these cells cannot make the substances such as albumin and clotting factors that the liver normally makes.

Liver cancer, also known as hepato-cellular carcinoma (HCC), can also develop in cirrhosis when some of the damaged liver cells start to multiply out of control. As liver function deteriorates, one or more complications may develop, often the first signs of the disease.  

 

Edema and ascites

When liver damage progresses to an advanced stage, fluid collects in the legs, called edema, and in the abdomen, called ascites. Ascites can lead to bacterial peritonitis, a serious infection.

Bruising and bleeding

When the liver slows or stops producing the proteins needed for blood clotting, a person will bruise or bleed easily.

Portal hypertension 

Normally, blood from the intestines and spleen is carried to the liver through the portal vein. But cirrhosis slows the normal flow of blood, which increases the pressure in the portal vein. This condition is called portal hypertension.

Esophageal varices and gastropathy

When portal hypertension occurs, it may cause enlarged blood vessels in the esophagus, called varices, or in the stomach, called gastropathy, or both. Enlarged blood vessels are more likely to burst due to thin walls and increased pressure. If they burst, serious bleeding can occur in the esophagus or upper stomach, requiring immediate medical attention.

Splenomegaly

When portal hypertension occurs, the spleen frequently enlarges and holds white blood cells and platelets, reducing the numbers of these cells in the blood. A low platelet count may be the first evidence that a person has developed cirrhosis.

Jaundice

Jaundice occurs when the diseased liver does not remove enough bilirubin from the blood, causing yellowing of the skin and whites of the eyes and darkening of the urine. Bilirubin is the pigment that gives bile its reddish-yellow color.

Gallstones

 If cirrhosis prevents bile from flowing freely to and from the gallbladder, the bile hardens as gallstones.

Sensitivity to medications

Cirrhosis slows the liver's ability to filter medications from the blood. When this occurs, medications act longer than expected and build up in the body. This causes a person to be more sensitive to medications and their side effects.

Hepatic encephalopathy

A failing liver cannot remove toxins from the blood, and they eventually accumulate in the brain. The buildup of toxins in the brain-called hepatic encephalopathy-can decrease mental function and cause coma. Signs of decreased mental function include confusion, personality changes, memory loss, trouble concentrating, and a change in sleep habits.

Insulin resistance and type 2 diabetes

Cirrhosis causes resistance to insulin-a hormone produced by the pancreas that enables the body to use glucose as energy. With insulin resistance, the body's muscle, fat, and liver cells do not use insulin properly. The pancreas tries to keep up with the demand for insulin by producing more, but excess glucose builds up in the bloodstream causing type 2 diabetes.

Liver cancer

Hepatocellular carcinoma is a type of liver cancer that can occur in people with cirrhosis. Hepatocellular carcinoma has a high mortality rate, but several treatment options are available.

Other problems

Cirrhosis can cause immune system dysfunction, leading to the risk of infection. Cirrhosis can also cause kidney and lung failure, known as hepatorenal and hepatopulmonary syndromes.

 

Symptoms of Cirrhosis

Initially, a person may have no symptoms at all. This is called compensated cirrhosis. In fact, a person may live many years with cirrhosis without being aware that his or her liver is scarred. This is because the pressure in the portal vein is not yet too high and there are still enough healthy liver cells to keep up with the body's needs.

However,  if nothing is done about the cause of cirrhosis, (continuing to drink heavily, for example) or if the underlying disease such as  hepatitis goes untreated, the pressure in the portal vein may increase to the point where the few remaining worker cells are overwhelmed. As cirrhosis progresses, the most common symptoms are:

  • weakness

  • fatigue

  • loss of appetite

  • nausea

  • vomiting

  • weight loss

  • abdominal pain and bloating when fluid accumulates in the abdomen

  • itching

  • spider-like blood vessels on the skin

Decompensated Cirrhosis

Cirrhosis is said to have progressed from compensated to decompensated cirrhosis when serious conditions develop as it worsens. These complications can be life-threatening and requires a new liver to replace the diseased one through a liver transplant.  As discussed earlier, another serious complication of cirrhosis is liver cancer, which may occur in the compensated or decompensated stage. There may be no signs of liver cancer until the tumor is large and causing pain.

Bleeding Varices

Internal bleeding from large blood vessels in the esophagus.

Ascites

A buildup of fluid in the belly. 

(pronounced "a-sigh-tees")

Encephalopathy

Confusion from the buildup of toxins in the blood.  (pronounced "en-sef-a-lop-a-thee")

Jaundice

Yellowing of the eyes and skin

Bleeding varices (internal bleeding)

Large blood vessels (varices) in the food tube get bigger and bigger over time and can burst open. When this happens, a person may vomit blood or have stool that is black and tarry. 

The risk of bleeding from varices can be reduced by blood pressure medicines known as beta-blockers or by a surgical procedure in which tiny rubber bands are tied around the varices.


Ascites (fluid in the belly)

Another problem caused by high pressure in the veins of the liver is ascites. Fluid leaks out into the belly and it begins to fill it up. This can make the abdomen enlarge like a balloon filled with water. The legs can get swollen too. This can be very uncomfortable. (Below is a photo of a severe case of ascites -- fluid in the abdomen). 

Eating can be a problem because there is less room for food. Even breathing can be a problem, especially when the person is lying down. But the most dangerous problem with ascites is infection, which can be life-threatening.

Ascites may go away with a low salt diet, and with diuretics (water pills) ordered by your provider. But sometimes a provider must actually drain the fluid from the belly using a special kind of needle.

Encephalopathy (confusion)

A liver that is working poorly may not be able to get rid of toxic substances like ammonia (which comes from the intestines), and it may allow these substances to go into the brain and cause confusion.

 

Besides confusion, toxins in the brain cause changes in sleep, mood, concentration, and memory. If extremely serious, it can even cause a coma. These are all symptoms of hepatic encephalopathy. With encephalopathy, a persons may have problems driving, writing, calculating, and performing other activities of daily living.

Signs of encephalopathy are trembling and hand "flapping." Encephalopathy may occur with an infection or internal bleeding, if constipated or with overuse of water pills or take tranquilizers or sleeping pills. 

Jaundice (yellowing of eyes and skin)

A liver that is working poorly cannot get rid of bilirubin, a substance that produces a yellowing of the eyes and skin called jaundice. Too much alcohol and some medicines can also lead to jaundice.

How is the severity of cirrhosis measured?

The "model for end-stage liver disease" (MELD) score measures the severity of cirrhosis. The MELD score was developed to predict the 90-day survival of people with advanced cirrhosis. The MELD score is based on three blood tests:

  • international normalized ratio (INR)-tests the clotting tendency of blood

  • bilirubin-tests the amount of bile pigment in the blood

  • creatinine-tests kidney function

MELD scores usually range between 6 and 40, with a score of 6 indicating the best likelihood of 90-day survival.

How is cirrhosis diagnosed?

The diagnosis of cirrhosis is usually based on the presence of a risk factor for cirrhosis, such as alcohol use or obesity, and is confirmed by physical examination, blood tests, and imaging. The doctor will ask about the person's medical history and symptoms and perform a thorough physical examination to observe for clinical signs of the disease. For example, on abdominal examination, the liver may feel hard or enlarged with signs of ascites. The doctor will order blood tests that may be helpful in evaluating the liver and increasing the suspicion of cirrhosis.

 

Patient with cirrhosis may have an upper endoscopy (pronounced "en-dahs-cup-ee") periodically (see figure at right). A thin tube with a camera can be inserted into the mouth to look for varices in the esophagus (food tube) and the stomach. The endoscopy is repeated every few years to monitor for varices.

To view the liver for signs of enlargement, reduced blood flow, or ascites, the doctor may order a computerized tomography (CT) scan, ultrasound, magnetic resonance imaging (MRI), or liver scan. The doctor may look at the liver directly by inserting a laparoscope into the abdomen. A laparoscope is an instrument with a camera that relays pictures to a computer screen.

A liver biopsy can confirm the diagnosis of cirrhosis but is not always necessary. A biopsy is usually done if the result might have an impact on treatment. The biopsy is performed with a needle inserted between the ribs or into a vein in the neck. Precautions are taken to minimize discomfort. A tiny sample of liver tissue is examined with a microscope for scarring or other signs of cirrhosis. Sometimes a cause of liver damage other than cirrhosis is found during biopsy. 

How is cirrhosis treated?

Treatment for cirrhosis depends on the cause of the disease and whether complications are present. The goals of treatment are to slow the progression of scar tissue in the liver and prevent or treat the complications of the disease. Hospitalization may be necessary for cirrhosis with complications.

Eating a nutritious diet

Because malnutrition is common in people with cirrhosis, a healthy diet is important in all stages of the disease. Health care providers recommend a meal plan that is well balanced. If ascites develops, a sodium-restricted diet is recommended. A person with cirrhosis should not eat raw shellfish, which can contain a bacterium that causes serious infection. To improve nutrition, the doctor may add a liquid supplement taken by mouth or through a nasogastric tube-a tiny tube inserted through the nose and throat that reaches into the stomach.

Avoiding alcohol and other substances

People with cirrhosis are encouraged not to consume any alcohol or illicit substances, as both will cause more liver damage. Because many vitamins and medications-prescription and over-the-counter-can affect liver function, a doctor should be consulted before taking them.

Treatment for cirrhosis also addresses specific complications

For edema and ascites, the doctor will recommend diuretics-medications that remove fluid from the body. Large amounts of ascitic fluid may be removed from the abdomen and checked for bacterial peritonitis. Oral antibiotics may be prescribed to prevent infection. Severe infection with ascites will require intravenous (IV) antibiotics.

Portal Hypertension

The doctor may prescribe a beta-blocker or nitrate for portal hypertension. Beta-blockers can lower the pressure in the varices and reduce the risk of bleeding. Gastrointestinal bleeding requires an immediate upper endoscopy to look for esophageal varices. The doctor may perform a band-ligation using a special device to compress the varices and stop the bleeding. People who have had varices in the past may need to take medicine to prevent future episodes.

Hepatic encephalopathy

Hepatic encephalopathy is treated by cleansing the bowel with lactulose-a laxative given orally or in enemas. Antibiotics are added to the treatment if necessary. Patients may be asked to reduce dietary protein intake. Hepatic encephalopathy may improve as other complications of cirrhosis are controlled.


Some people with cirrhosis who develop hepatorenal failure must undergo regular hemodialysis treatment, which uses a machine to clean wastes from the blood. Medications are also given to improve blood flow through the kidneys.

Other treatments

Other treatments address the specific causes of cirrhosis. Treatment for cirrhosis caused by hepatitis depends on the specific type of hepatitis. For example, interferon and other antiviral drugs are prescribed for viral hepatitis, and autoimmune hepatitis requires corticosteroids and other drugs that suppress the immune system.

Medications are given to treat various symptoms of cirrhosis, such as itching and abdominal pain.

When is a liver transplant indicated for cirrhosis?

A liver transplant is considered necessary when complications cannot be controlled by treatment. Liver transplantation is a major operation in which the diseased liver is removed and replaced with a healthy one from an organ donor. A team of health professionals determines the risks and benefits of the procedure for each patient. Survival rates have improved over the past several years because of drugs that suppress the immune system and keep it from attacking and damaging the new liver.

The number of people who need a liver transplant far exceeds the number of available organs. A person needing a transplant must go through a complicated evaluation process before being added to a long transplant waiting list. Generally, organs are given to people with the best chance of living the longest after a transplant. Survival after a transplant requires intensive follow-up and cooperation on the part of the patient and caregiver.​

When should hospice care be considered for patients with end-stage liver disease?

Regardless of how accomplished a patient’s physician is or how loving and supportive the family has been, there may come a time when continued aggressive medical treatment may be looked at as more of a burden than a benefit for all parties involved. Patients with end-stage liver disease often experience fatigue, weakness, jaundice (yellowing of the skin and the whites of the eyes), swelling of the legs and abdomen, appetite loss and weight loss, nausea, itchy skin and hiccups.

Even if the patient has opted out of additional medical treatments for their liver disease, their comfort, safety and dignity need to be preserved along with addressing their personal concerns and wishes. With an interdisciplinary hospice care team they can provide care and support for patients with liver failure and their families.

The patient’s physician(s) may recommend hospice care when the time is appropriate. Oftentimes, patients and their families may have to be their own advocates to initiate the hospice care they desire. The patient, their family, or the patient’s doctor may request an evaluation and consultation with with the hospice staff to determine if hospice care is an appropriate option. 

End-Stage

Multiple Sclerosis (MS)

Please watch this 2:28 minute video explaining Multiple Sclerosis. 

What is Multiple Sclerosis?

 

 

 

 

 

 

Overview

Multiple sclerosisOpen pop-up dialog box

Multiple sclerosis (MS) is a potentially disabling disease of the brain and spinal cord (central nervous system).

In MS, the immune system attacks the protective sheath (myelin) that covers nerve fibers and causes communication problems between your brain and the rest of your body. Eventually, the disease can cause permanent damage or deterioration of the nerves.

Signs and symptoms of MS vary widely and depend on the amount of nerve damage and which nerves are affected. Some people with severe MS may lose the ability to walk independently or at all, while others may experience long periods of remission without any new symptoms.

There's no cure for multiple sclerosis. However, treatments can help speed recovery from attacks, modify the course of the disease and manage symptoms.

Symptoms

Myelin damage and the nervous system.

Multiple sclerosis signs and symptoms may differ greatly from person to person and over the course of the disease depending on the location of affected nerve fibers. Symptoms often affect movement, such as:

  • Numbness or weakness in one or more limbs that typically occurs on one side of your body at a time, or your legs and trunk

  • Electric-shock sensations that occur with certain neck movements, especially bending the neck forward (Lhermitte sign)

  • Tremor, lack of coordination or unsteady gait

Vision problems are also common, including:

  • Partial or complete loss of vision, usually in one eye at a time, often with pain during eye movement

  • Prolonged double vision

  • Blurry vision

Multiple sclerosis symptoms may also include:

  • Slurred speech

  • Fatigue

  • Dizziness

  • Tingling or pain in parts of your body

  • Problems with bowel and bladder function

When to see a doctor

See a doctor if you experience any of the above symptoms for unknown reasons.

Disease course

Most people with MS have a relapsing-remitting disease course. They experience periods of new symptoms or relapses that develop over days or weeks and usually improve partially or completely. These relapses are followed by quiet periods of disease remission that can last months or even years.

Small increases in body temperature can temporarily worsen signs and symptoms of MS, but these aren't considered true disease relapses.

At least 50% of those with relapsing-remitting MS eventually develop a steady progression of symptoms, with or without periods of remission, within 10 to 20 years from disease onset. This is known as secondary-progressive MS.

The worsening of symptoms usually includes problems with mobility and gait. The rate of disease progression varies greatly among people with secondary-progressive MS.

Some people with MS experience a gradual onset and steady progression of signs and symptoms without any relapses, known as primary-progressive MS.

Causes

The cause of multiple sclerosis is unknown. It's considered an autoimmune disease in which the body's immune system attacks its own tissues. In the case of MS, this immune system malfunction destroys the fatty substance that coats and protects nerve fibers in the brain and spinal cord (myelin).

Myelin can be compared to the insulation coating on electrical wires. When the protective myelin is damaged and the nerve fiber is exposed, the messages that travel along that nerve fiber may be slowed or blocked.

It isn't clear why MS develops in some people and not others. A combination of genetics and environmental factors appears to be responsible.

Risk factors

These factors may increase your risk of developing multiple sclerosis:

  • Age. MS can occur at any age, but onset usually occurs around 20 and 40 years of age. However, younger and older people can be affected.

  • Sex. Women are more than two to three times as likely as men are to have relapsing-remitting MS.

  • Family history. If one of your parents or siblings has had MS, you are at higher risk of developing the disease.

  • Certain infections. A variety of viruses have been linked to MS, including Epstein-Barr, the virus that causes infectious mononucleosis.

  • Race. White people, particularly those of Northern European descent, are at highest risk of developing MS. People of Asian, African or Native American descent have the lowest risk.

  • Climate. MS is far more common in countries with temperate climates, including Canada, the northern United States, New Zealand, southeastern Australia and Europe

  • Vitamin D. Having low levels of vitamin D and low exposure to sunlight is associated with a greater risk of MS.

  • Certain autoimmune diseases. You have a slightly higher risk of developing MS if you have other autoimmune disorders such as thyroid disease, pernicious anemia, psoriasis, type 1 diabetes or inflammatory bowel disease.

  • Smoking. Smokers who experience an initial event of symptoms that may signal MS are more likely than nonsmokers to develop a second event that confirms relapsing-remitting MS.

Complications

People with multiple sclerosis may also develop:

  • Muscle stiffness or spasms

  • Paralysis, typically in the legs

  • Problems with bladder, bowel or sexual function

  • Mental changes, such as forgetfulness or mood swings

  • Depression

  • Epilepsy

Diagnosis

Neurological exam

There are no specific tests for MS. Instead, a diagnosis of multiple sclerosis often relies on ruling out other conditions that might produce similar signs and symptoms, known as a differential diagnosis.

Your doctor is likely to start with a thorough medical history and examination.

Spinal tap (lumbar puncture)

MRI multiple sclerosis lesions

Your doctor may then recommend:

  • Blood tests, to help rule out other diseases with symptoms similar to MS. Tests to check for specific biomarkers associated with MS are currently under development and may also aid in diagnosing the disease.

  • Spinal tap (lumbar puncture), in which a small sample of cerebrospinal fluid is removed from your spinal canal for laboratory analysis. This sample can show abnormalities in antibodies that are associated with MS. A spinal tap can also help rule out infections and other

       conditions with symptoms similar to MS.

  • MRI, which can reveal areas of MS (lesions) on your brain and spinal cord. You may receive an intravenous injection of a contrast material to highlight lesions that indicate your disease is in an active phase.

  • Evoked potential tests, which record the electrical signals produced by your nervous system in response to stimuli. An evoked potential test may use visual stimuli or electrical stimuli. In these tests, you watch a moving visual pattern, or short electrical impulses are applied to nerves in your legs or arms. Electrodes measure how quickly the information travels down your nerve pathways.

In most people with relapsing-remitting MS, the diagnosis is fairly straightforward and based on a pattern of symptoms consistent with the disease and confirmed by brain imaging scans, such as MRI.

Diagnosing MS can be more difficult in people with unusual symptoms or progressive disease. In these cases, further testing with spinal fluid analysis, evoked potentials and additional imaging may be needed.

Treatments for MS attacks

  • Corticosteroids, such as oral prednisone and intravenous methylprednisolone, are prescribed to reduce nerve inflammation. Side effects may include insomnia, increased blood pressure, increased blood glucose levels, mood swings and fluid retention.

  • Plasma exchange (plasmapheresis). The liquid portion of part of your blood (plasma) is removed and separated from your blood cells. The blood cells are then mixed with a protein solution (albumin) and put back into your body. Plasma exchange may be used if your symptoms are new, severe and haven't responded to steroids.

Treatments to modify progression

For primary-progressive MS, ocrelizumab (Ocrevus) is the only FDA-approved disease-modifying therapy (DMT). Those who receive this treatment are slightly less likely to progress than those who are untreated.

For relapsing-remitting MS, several disease-modifying therapies are available.

Much of the immune response associated with MS occurs in the early stages of the disease. Aggressive treatment with these medications as early as possible can lower the relapse rate, slow the formation of new lesions, and potentially reduce risk of brain atrophy and disability accumulation.

Many of the disease-modifying therapies used to treat MS carry significant health risks. Selecting the right therapy for you will depend on careful consideration of many factors, including duration and severity of disease, effectiveness of previous MS treatments, other health issues, cost, and child-bearing status.

Treatment options for relapsing-remitting MS include injectable and oral medications.

(www.mayoclinic.org)

What Is Prostate Cancer?

The Facts:

Prostate cancer represents the second most common cancer in men worldwide and the fifth most common cause of cancer death in men; in the United States, it is the most common cancer in men and the second most common cause of cancer deaths in men. Acinar adenocarcinoma of the prostate comprises 90-95% of prostate cancers diagnosed.

Cancer starts when cells in the body begin to grow out of control. Cells in nearly any part of the body can become cancer cells, and can then spread to other areas of the body. 

Prostate cancer begins when cells in the prostate gland start to grow out of control. The prostate is a gland found only in males. It makes some of the fluid that is part of semen.

The prostate is below the bladder (the hollow organ where urine is stored) and in front of the rectum (the last part of the intestines). Just behind the prostate are glands called seminal vesicles that make most of the fluid for semen. The urethra, which is the tube that carries urine and semen out of the body through the penis, goes through the center of the prostate.

 

 

The size of the prostate can change as a man ages. In younger men, it is about the size of a walnut, but it can be much larger in older men.

Types of prostate cancer

Almost all prostate cancers are adenocarcinomas. These cancers develop from the gland cells (the cells that make the prostate fluid that is added to the semen).

Other types of cancer that can start in the prostate include:

  • Small cell carcinomas

  • Neuroendocrine tumors (other than small cell carcinomas)

  • Transitional cell carcinomas

  • Sarcomas

 

These other types of prostate cancer are rare. If you are told you have prostate cancer, it is almost certain to be an adenocarcinoma.

Some prostate cancers grow and spread quickly, but most grow slowly. In fact, autopsy studies show that many older men (and even some younger men) who died of other causes also had prostate cancer that never affected them during their lives. In many cases, neither they nor their doctors even knew they had it.

Possible pre-cancerous conditions of the prostate

Some research suggests that prostate cancer starts out as a pre-cancerous condition, although this is not yet known for sure. These conditions are sometimes found when a man has a prostate biopsy (removal of small pieces of the prostate to look for cancer).

Prostatic intraepithelial neoplasia (PIN)

In PIN, there are changes in how the prostate gland cells look when seen with a microscope, but the abnormal cells don’t look like they are growing into other parts of the prostate (like cancer cells would). Based on how abnormal the patterns of cells look, they are classified as:

  • Low-grade PIN: The patterns of prostate cells appear almost normal.

  • High-grade PIN: The patterns of cells look more abnormal.

 

Low-grade PIN is not thought to be related to a man’s risk of prostate cancer. On the other hand, high-grade PIN is thought to be a possible precursor to prostate cancer. If you have a prostate biopsy and high-grade PIN is found, there is a greater chance that you might develop prostate cancer over time.

PIN begins to appear in the prostates of some men as early as in their 20s. But many men with PIN will never develop prostate cancer.

Proliferative inflammatory atrophy (PIA)

In PIA, the prostate cells look smaller than normal, and there are signs of inflammation in the area. PIA is not cancer, but researchers believe that PIA may sometimes lead to high-grade PIN, or perhaps directly to prostate cancer.

Prostate Cancer Risk Factors

A risk factor is anything that raises your risk of getting a disease such as cancer. Different cancers have different risk factors. Some risk factors, like smoking, can be changed. Others, like a person’s age or family history, can’t be changed.

But having a risk factor, or even several, does not mean that you will get the disease. Many people with one or more risk factors never get cancer, while others who get cancer may have had few or no known risk factors.

Researchers have found several factors that might affect a man’s risk of getting prostate cancer.

 

Age

Prostate cancer is rare in men younger than 40, but the chance of having prostate cancer rises rapidly after age 50. About 6 in 10 cases of prostate cancer are found in men older than 65.

Race/ethnicity

Prostate cancer develops more often in African-American men and in Caribbean men of African ancestry than in men of other races. And when it does develop in these men, they tend to be younger. Prostate cancer occurs less often in Asian-American and Hispanic/Latino men than in non-Hispanic whites. The reasons for these racial and ethnic differences are not clear.

Geography

Prostate cancer is most common in North America, northwestern Europe, Australia, and on Caribbean islands. It is less common in Asia, Africa, Central America, and South America.

The reasons for this are not clear. More intensive screening for prostate cancer in some developed countries probably accounts for at least part of this difference, but other factors such as lifestyle differences (diet, etc.) are likely to be important as well. For example, Asian Americans have a lower risk of prostate cancer than white Americans, but their risk is higher than that of men of similar ethnic backgrounds living in Asia.

Family history

Prostate cancer seems to run in some families, which suggests that in some cases there may be an inherited or genetic factor. Still, most prostate cancers occur in men without a family history of it.

Having a father or brother with prostate cancer more than doubles a man’s risk of developing this disease. (The risk is higher for men who have a brother with the disease than for those who have a father with it.) The risk is much higher for men with several affected relatives, particularly if their relatives were young when the cancer was found.

Gene changes

Several inherited gene changes (mutations) seem to raise prostate cancer risk, but they probably account for only a small percentage of cases overall. For example:

  • Inherited mutations of the BRCA1 or BRCA2 genes, which are linked to an increased risk of breast and ovarian cancers in some families, can also increase prostate cancer risk in men (especially mutations in BRCA2).

  • Men with Lynch syndrome (also known as hereditary non-polyposis colorectal cancer, or HNPCC), a condition caused by inherited gene changes, have an increased risk for a number of cancers, including prostate cancer.

 

Other inherited gene changes can also raise a man’s risk of prostate cancer. 

Factors with less clear effects on prostate cancer risk:

Diet

The exact role of diet in prostate cancer is not clear, but several factors have been studied.

Men who eat a lot of dairy products appear to have a slightly higher chance of getting prostate cancer.

Some studies have suggested that men who consume a lot of calcium (through food or supplements) may have a higher risk of developing prostate cancer. But most studies have not found such a link with the levels of calcium found in the average diet, and it’s important to note that calcium is known to have other important health benefits.

Obesity

Being obese (very overweight) does not seem to increase the overall risk of getting prostate cancer.

Some studies have found that obese men have a lower risk of getting a low-grade (slower growing) form of the disease, but a higher risk of getting more aggressive (faster growing) prostate cancer. The reasons for this are not clear.

Some studies have also found that obese men may be at greater risk for having more advanced prostate cancer and of dying from prostate cancer, but not all studies have found this.

Smoking

Most studies have not found a link between smoking and getting prostate cancer. Some research has linked smoking to a possible small increased risk of dying from prostate cancer, but this finding needs to be confirmed by other studies.

Chemical exposures

There is some evidence that firefighters can be exposed to chemicals that may increase their risk of prostate cancer.

A few studies have suggested a possible link between exposure to Agent Orange, a chemical used widely during the Vietnam War, and the risk of prostate cancer, although not all studies have found such a link. The National Academy of Medicine considers there to be “limited/suggestive evidence” of a link between Agent Orange exposure and prostate cancer. 

Inflammation of the prostate

Some studies have suggested that prostatitis (inflammation of the prostate gland) may be linked to an increased risk of prostate cancer, but other studies have not found such a link. Inflammation is often seen in samples of prostate tissue that also contain cancer. The link between the two is not yet clear, and this is an active area of research.

Sexually transmitted infections

Researchers have looked to see if sexually transmitted infections (like gonorrhea or chlamydia) might increase the risk of prostate cancer, because they can lead to inflammation of the prostate. So far, studies have not agreed, and no firm conclusions have been reached.

Vasectomy

Some studies have suggested that men who have had a vasectomy (minor surgery to make men infertile) have a slightly increased risk for prostate cancer, but other studies have not found this. Research on this possible link is still under way.

Can Prostate Cancer Be Found Early?

Screening is testing to find cancer in people before they have symptoms. For some types of cancer, screening can help find cancers at an early stage, when they are likely to be easier to treat.

Prostate cancer can often be found early by testing for prostate-specific antigen (PSA) levels in a man’s blood. Another way to find prostate cancer is the digital rectal exam (DRE). For a DRE, the doctor puts a gloved, lubricated finger into the rectum to feel the prostate gland.

Concerns about prostate cancer screening

If prostate cancer is found as a result of screening, it will probably be at an earlier, more treatable stage than if no screening were done. While this might make it seem like prostate cancer screening would always be a good thing, there are still issues surrounding screening that make it unclear if the benefits outweigh the risks for most men.

Possible inaccurate or unclear test results

As an example, neither the PSA test nor the DRE is 100% accurate. These tests can sometimes have abnormal results even when a man does not have cancer (known as a false-positive result), or normal results even when a man does have cancer (known as a false-negative result). Unclear test results can cause confusion and anxiety. False-positive results can lead some men to get prostate biopsies (with small risks of pain, infection, and bleeding) when they don’t have cancer. And false-negative results can give some men a false sense of security even though they might actually have cancer.

Over-diagnosis and over-treatment

Another important issue is that even if screening detects prostate cancer, doctors sometimes can’t tell if the cancer is truly dangerous (and therefore needs to be treated). Finding and treating all prostate cancers early might seem to make sense, but some prostate cancers grow so slowly that they would never cause a man problems during his lifetime. 

Because of screening, some men may be diagnosed with a prostate cancer that they would have never known about otherwise. It would never have led to their death, or even caused any symptoms. Finding a ‘disease’ like this that would never cause problems is known as over-diagnosis.

A problem with over-diagnosis in prostate cancer is that many of these men might still be treated with either surgery or radiation, either because the doctor can’t be sure how quickly the cancer might grow and spread, or because the man is uncomfortable knowing he has cancer and is not getting any treatment. Treatment of a cancer that would never have caused any problems is known as over-treatment. The major downside with this is that even if they weren’t needed, treatments like surgery and radiation can still have urinary, bowel, and/or sexual side effects that can seriously affect a man’s quality of life.

Men and their doctors may end up struggling to decide if treatment is needed or if the cancer can just be closely watched without being treated right away (an approach called, "watchful waiting or active surveillance"). Even when men are not treated right away, they still need regular blood PSA tests and prostate biopsies to determine their need for treatment in the future. These tests are linked with risks of anxiety, pain, infection, and bleeding.

Benefits of screening in studies have not been clear

Doctors are still studying if screening tests will lower the risk of death from prostate cancer. The most recent results from 2 large studies were conflicting, and didn’t offer clear answers.

  • Early results from a large study done in the United States found that annual screening with PSA and DRE did detect more prostate cancers than in men not screened, but this screening did not lower the death rate from prostate cancer. However, questions have been raised about this study, because some men in the non-screening group actually were screened during the study, which might have affected the results. 

  • A European study did find a lower risk of death from prostate cancer with PSA screening (done about once every 4 years), but the researchers estimated that about 781 men would need to be screened (and 27 cancers detected) to prevent one death from prostate cancer.

  • Neither of these studies has shown that PSA screening helps men live longer overall (that is, that it lowers the overall death rate).

 

Prostate cancer is often slow-growing, so the effects of screening in these studies might become clearer in the coming years. Both of these studies are being continued to see if longer follow-up will give clearer results. Prostate cancer screening is being studied in several other large studies, as well.

For now, the American Cancer Society recommends that men thinking about getting tested for prostate cancer learn as much as they can so they can make informed decisions based on available information, discussions with their doctor, and their own views on the possible benefits, risks, and limits of prostate cancer screening.

(www.cancer.org)

Incidence & Mortality of Patients

with Prostate Cancer Worldwide

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