ReFarat Jaundice

7/30/2019 ReFarat Jaundice

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LIVER

The liver is a vital organ present in vertebrates and some other animals. It has a wide range of

functions, including detoxification, protein synthesis, and production of biochemicals necessary for

digestion. The liver is necessary for survival; there is currently no way to compensate for the absence of

liver function.

This organ plays a major role in metabolism and has a number of functions in the body, including

glycogen storage, decomposition of red blood cells,plasma protein synthesis, hormone production, and

detoxification. It lies below the diaphragm in the thoracic region of the abdomen. It produces bile, an

alkaline compound which aids in digestion, via the emulsification of lipids. The liver's highly specialized

tissues regulate a wide variety of high-volume biochemical reactions, including the synthesis and

breakdown of small and complex molecules, many of which are necessary for normal vital functions.

ANATOMY

The liver is a reddish brown organ with four lobes of unequal size and shape. A human liver

normally weighs between 1.41.6 kg and is a soft, pinkish-brown, triangular organ. It is both the largest

internal organ (the skin being the largest organ overall) and the largest gland in the human body.

It is located in the right upper quadrant of the abdominal cavity, resting just below the

diaphragm. The liver lies to the right of the stomach and overlies the gallbladder. It is connected to two

large blood vessels, one called the hepatic artery and one called the portal vein. The hepatic artery

carries blood from the aorta whereas the portal vein carries blood containing digested nutrients from

the small intestine and the descending colon. These blood vessels subdivide into capillaries which then

lead to a lobule. Each lobule is made up of millions of hepatic cells which are the basic metabolic cells.

Figure 1 : Normal anatomy of the liver. CBD = common bile duct, CD = cystic duct, CHD = common

hepatic duct, HA = hepatic artery, IVC = inferior vena cava, LHA = left hepatic artery, LHD = left hepatic

duct, LHV = left hepatic vein, LPV = left portal vein, MHV = middle hepatic vein, PV = portal vein, RHA =

right hepatic artery, RHD = right hepatic duct, RHV = right hepatic vein, RPV = right portal vein.


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BILIARY FLOW

The term biliary tree is derived from the arboreal branches of the bile ducts. The bile produced

in the liver is collected in bile canaliculi, which merge to form bile ducts. Within the liver, these ducts are

called intrahepatic (within the liver) bile ducts, and once they exit the liver they are considered

extrahepatic (outside the liver).

The intrahepatic ducts eventually drain into the right and left hepatic ducts, which merge to

form the common hepatic duct. The cystic duct from the gallbladder joins with the common hepatic

duct to form the common bile duct. Bile can either drain directly into the duodenum via the common

bile duct or be temporarily stored in the gallbladder via the cystic duct. The common bile duct and the

pancreatic duct enter the second part of the duodenum together at the ampulla of Vater.


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JAUNDICE

Jaundice, (also known as icterus, attributive adjective: icteric) is a yellowish pigmentation of the

skin, the conjunctival membranes over the sclerae (whites of the eyes), and other mucous membranes

caused by hyperbilirubinemia (increased levels of bilirubin in the blood). This hyperbilirubinemia

subsequently causes increased levels of bilirubin in the extracellular fluids.

Bilirubin is a yellow chemical in hemoglobin, the substance that carries oxygen in your red blood

cells. As red blood cells break down, your body builds new cells to replace them. The old ones are

processed by the liver. If the liver cannot handle the blood cells as they break down, bilirubin builds up

in the body and your skin may look yellow.

Bilirubin is created by the activity of biliverdin reductase on biliverdin, a green tetrapyrrolic bile

pigment which is also a product of heme catabolism. Bilirubin, when oxidized, reverts to become

biliverdin once again. This cycle, in addition to the demonstration of the potent antioxidant activity of

bilirubin, has led to the hypothesis that bilirubin's main physiologic role is as a cellular antioxidant.

Tissue deposition of bilirubin occurs only in the presence of serum hyperbilirubinemia and is asign of either liver disease or, less often, a hemolytic disorder. The degree of serum bilirubin elevation

can be estimated by physical examination. Slight increases in serum bilirubin are best detected by

examining the sclerae which have a particular affinity for bilirubin due to their high elastin content.

The presence of sclera icterus indicates a serum bilirubin of at least 3.0 mg/dL. The ability to

detect scleral icterus is made more difficult if the examining room has fluorescent lighting. If the

examiner suspects scleral icterus, a second place to examine is underneath the tongue. As serum

bilirubin levels rise, the skin will eventually become yellow in light-skinned patients and even green if

the process is longstanding; the green color is produced by oxidation of bilirubin to biliverdin.

The differential diagnosis for yellowing of the skin is limited. In addition to jaundice, itincludes carotenoderma, the use of the drug quinacrine, and excessive exposure to phenols.

Carotenoderma is the yellow color imparted to the skin by the presence of carotene; it occurs in healthy

individuals who ingest excessive amounts of vegetables and fruits that contain carotene, such as carrots,

leafy vegetables, squash, peaches, and oranges. Unlike jaundice, where the yellow coloration of the skin

is uniformly distributed over the body, in carotenoderma the pigment is concentrated on the palms,


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soles, forehead and nasolabial folds. Carotenoderma can be distinguished from jaundice by the sparing

of the sclerae.

Another sensitive indicator of increased serum bilirubin is darkening of the urine, which is due to

the renal excretion of conjugated bilirubin. Patients often describe their urine as tea or cola colored.

Bilirubinuria indicates an elevation of the direct serum bilirubin fraction and therefore the presence of

liver disease.

Increased serum bilirubin levels occur when an imbalance exists between bilirubin production

and clearance. A logical evaluation of the patient who is jaundiced require understanding of bilirubin

production and metabolism.

Types of bilirubin

Unconjugated

Erythrocytes (red blood cells) generated in the bone marrow are disposed of in the spleen when they

get old or damaged. This releases hemoglobin, which is broken down to heme as the globin parts are

turned into amino acids. The heme is then turned into unconjugated bilirubin in the reticuloendothelial

cells of the spleen. This unconjugated bilirubin is not soluble in water. It is then bound to albumin and

sent to the liver.

Conjugated

In the liver it is conjugated with glucuronic acid by the enzyme Glucuronyltransferase, making it soluble

in water. Much of it goes into the bile and thus out into the small intestine. Some of the conjugated

bilirubin remains in the large intestine and is metabolised by colonic bacteria to urobilinogen, which is

further metabolized to stercobilinogen, and finally oxidised to stercobilin. This stercobilin gives feces its

brown color. Some of the urobilinogen is reabsorbed and excreted in the urine along with an oxidizedform, urobilin.

In urine

Normally, a tiny amount of bilirubin is excreted in the urine if any. If the livers function is impaired or

when biliary drainage is blocked, some of the conjugated bilirubin leaks out of the hepatocytes and

appears in the urine, turning it dark amber. The presence of this conjugated bilirubin in the urine can be

clinically analyzed, and is reported as an increase in urine bilirubin. However, in disorders involving

hemolytic anemia, an increased number of red blood cells are broken down, causing an increase in the

amount of unconjugated bilirubin in the blood. As stated above, the unconjugated bilirubin is not water

soluble, and thus one will not see an increase in bilirubin in the urine. Because there is no problem with

the liver or bile systems, this excess unconjugated bilirubin will go through all of the normal processing

mechanisms that occur (e.g., conjugation, excretion in bile, metabolism to urobilinogen, reabsorption)

and will show up as an increase in urine urobilinogen. This difference between increased urine bilirubin

and increased urine urobilinogen helps to distinguish between various disorders in those systems.


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Pre-hepatic : E.g. (hemolytic anemia due to malaria)

Laboratory findings include:

Urine: no bilirubin present, urobilirubin > 2 units (i.e., hemolytic anemia causes increased heme

metabolism; exception: infants where gut flora has not developed).

Serum: increased unconjugated bilirubin.

Kernicterus is associated with increased unconjugated bilirubin

Hepatic

Hepatic jaundice causes include acute hepatitis, hepatotoxicity and alcoholic liver disease, whereby cell

necrosis reduces the liver's ability to metabolize and excrete bilirubin leading to a buildup in the blood.

Less common causes include primary biliary cirrhosis, Gilbert's syndrome (a genetic disorder of bilirubin

metabolism which can result in mild jaundice, which is found in about 5% of the population), Crigler-

Najjar syndrome, metastatic carcinoma and Niemann-Pick disease, type C. Jaundice seen in the

newborn, known as neonatal jaundice, is common, occurring in almost every newborn as hepatic

machinery for the conjugation and excretion of bilirubin does not fully mature until approximately two

weeks of age.


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Laboratory findings include:

Urine: Conjugated bilirubin present, urobilirubin > 2 units but variable (except in children). Kernicterus is

a condition not associated with increased conjugated bilirubin.

Post-hepatic (OBSTRUCTIVE)

Post-hepatic jaundice, also called obstructive jaundice, is caused by an interruption to the drainage of

bile in the biliary system. The most common causes are gallstones in the common bile duct, and

pancreatic cancer in the head of the pancreas. Also, a group of parasites known as "liver flukes" can live

in the common bile duct, causing obstructive jaundice. Other causes include strictures of the common

bile duct, biliary atresia, ductal carcinoma, pancreatitis and pancreatic pseudocysts. A rare cause of

obstructive jaundice is Mirizzi's syndrome.

The presence of pale stools and dark urine suggests an obstructive or post-hepatic cause as normal feces

get their color from bile pigments. However, although pale stools and dark urine are a feature of biliary

obstruction, they can occur in many intra-hepatic illnesses and are therefore not a reliable clinicalfeature to distinguish obstruction from hepatic causes of jaundice.

Patients also can present with elevated serum cholesterol, and often complain of severe itching or

"pruritus".

Not one test can differentiate between various classifications of jaundice. A combination of liver

function tests is essential to arrive at a diagnosis.

TYPES OF JAUNDICE


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Diagnosis of jaundice

Most of the time jaundice is recognized by a yellowing of the skin and in the whites of the eyes. Also in

bowel movements may appear light in color since bilirubin is responsible for making stools dark. Urine

may become dark or brownish is color from bilirubin being excreted from the body through the urine.

One of the most serious side effects of jaundice is severe itching. The itching can become so severe thata person may not be able to control themselves from scratching.

Once jaundice is diagnosed it is important to determine the under-lying cause of the problem.

Sometimes the cause is already known and jaundice appears later as a side effect. Treating the jaundice

may be simple in some cases or difficult depending on the cause. Jaundice will only go away once the

original condition is treated.

Table of diagnostic test

Function test

Pre-hepatic

Jaundice Hepatic Jaundice Post-hepatic Jaundice

Total bilirubinNormal/

IncreasedIncreased

Conjugated bilirubin Normal Increased Increased

Unconjugated bilirubinNormal/

IncreasedIncreased Normal

UrobilinogenNormal/

IncreasedIncreased Decreased/ Negative

Urine Color Normal(urobilinogen) Dark (urobilinogen + conjugatedbilirubin) Dark (congujatedbilirubin)

Stool Color Normal Pale

Alkaline phosphatase

levels

Normal

Increased

Alanine transferase and

Aspartate transferase

levels

Increased

Conjugated Bilirubin in

Urine

Not Present Present


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Differential diagnosis of jaundice

OBSTRUCTIVE / MECHANICAL JAUNDICE

The liver plays a very important role in the human body. It produces around one liter of bile

every day, which helps the food get digested easily. The bile is stored in the gallbladder and it empties in

the upper intestine providing it with necessary bile. Any obstruction in this process causes obstructive

jaundice. Due the blockage the bile overflows into the blood and increase the level of bilirubin in the

blood. It can also causes various other infections in the body, so it is important to treat obstructive

jaundice as soon as possible.

One of the most frequent causes of obstructive jaundice is gallstones. Gallstones are pebble like

deposits in the gallbladder which occur when cholesterol and other things found in the bile become

hardened. Gallstones can be very tiny, almost too small to see, or they can be very large, nearing the

size of a golf ball. If a stone is too large it can cause an obstruction when it tries to pass through the bile

duct system. If the stone is not firmly stuck then the jaundice may not last very long however if it does

become lodged then you will develop symptoms of jaundice and other symptoms as well.

Another common cause of obstructive jaundice is tumors of the liver, pancreas or bile duct. Cancer of

the pancreas or liver can cause obstructive jaundice as well. Hepatitis, which is an inflammation of theliver caused by a virus, can cause obstructive jaundice and alcoholism is a big factor as well. Taking

certain medications can contribute to obstructive jaundice as can experiencing trauma to the liver area.

Primary biliary cirrhosis is a disease of the liver that slowly destroys the bile ducts. Sclerosing Cholangitis

is hardening and scarring of tissues of the bile duct caused by inflammation and Biliary Atresia is a

condition in which the bile ducts that carry the bile out of the liver are missing or damaged. Other


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causes of obstructive jaundice can include having parasites or worms, which is possible but rare, and

scarring to the liver from previous surgery.

SYMPTOMS

Due to increased levels of bilirubin in the blood the skin and eyes appear pale yellow in color.

Bilirubin also causes dark yellow color urine and pale colored stools. These are some of the obvious

obstructive jaundice symptoms. The other symptoms include:

Fever Weight loss Diarrhea smelly and bulky stools Upper abdominal pain Enlarged liver Enlarged spleen Malaise Itching skin Nausea

Once obstructive jaundice has been diagnosed treatment should begin immediately. Treatment

for obstructive jaundice includes surgical removal of the obstruction using a procedure called ERCP

(Endoscopic retrograde cholangiopancreatography). With this procedure you will be sedated and the

doctor will use an endoscope that will be inserted into your mouth, down your esophagus, into the

stomach and into the intestine looking for the blockage. Another procedure that can be used is

laparoscopic surgery which is where the surgeon makes one inch incisions to reach the obstruction.

Other treatment might be to cease all medications that are suspected in causing liver inflammation and

antibiotics may be started to treat infection. In cases of obstructive jaundice caused by cancer,

treatments may include chemotherapy, radiation and biliary drainage. Surgery is rarely used in these

cases. With biliary atresia a liver transplant may be necessary, especially in children.

Some complications of obstructive jaundice can include confusion, fatigue, and vitamin k

deficiency. Vitamin K deficiency can cause the blood to be unable to clot effectively which can then lead

to excessive bleeding and bruising. Cirrhosis of liver, acute liver failure, and brain disorders are caused

by the liver not filtering the waste products out of the blood properly. Malabsorption syndrome can be

another side effect of obstructive jaundice which means the body is not able to absorb nutrients

properly.

There are many reasons in which obstructive jaundice can cause serious harm to the body

therefore obstructive jaundice requires immediate medical attention.


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Gallbladder stones Pancreatic tumor

GALLBLADDER STONES

Gallstones are small, pebble-like substances that develop in the gallbladder. The gallbladder is a small,

pear-shaped sac located below your liver in the right upper abdomen. Gallstones form when liquid

stored in the gallbladder hardens into pieces of stone-like material. The liquidcalled bilehelps the

body digest fats. Bile is made in the liver, then stored in the gallbladder until the body needs it. The

gallbladder contracts and pushes the bile into a tubecalled the common bile ductthat carries it to

the small intestine, where it helps with digestion.

Bile contains water, cholesterol, fats, bile salts, proteins, and bilirubina waste product. Bile salts break

up fat, and bilirubin gives bile and stool a yellowish-brown color. If the liquid bile contains too much

cholesterol, bile salts, or bilirubin, it can harden into gallstones.

The two types of gallstones are cholesterol stones and pigment stones. Cholesterol stones are usually

yellow-green and are made primarily of hardened cholesterol. They account for about 80 percent of

gallstones. Pigment stones are small, dark stones made of bilirubin. Gallstones can be as small as a grain

of sand or as large as a golf ball. The gallbladder can develop just one large stone, hundreds of tiny

stones, or a combination of the two.

Gallstones can block the normal flow of bile if they move from the gallbladder and lodge in any of the

ducts that carry bile from the liver to the small intestine. The ducts include :

the hepatic ducts, which carry bile out of the liver cystic duct, which takes bile to and from the gallbladder common bile duct, which takes bile from the cystic and hepatic ducts to the small intestineIf any of the bile ducts remain blocked for a significant period of time, severe damage or infection

can occur in the gallbladder, liver, or pancreas. Left untreated, the condition can be fatal. Warning signs

of a serious problem are fever, jaundice, and persistent pain.


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Scientists believe cholesterol stones form when bile contains too much cholesterol, too much

bilirubin, or not enough bile salts, or when the gallbladder does not empty completely or often enough.

The reason these imbalances occur is not known.

The cause of pigment stones is not fully understood. The stones tend to develop in people who

have liver cirrhosis, biliary tract infections, or hereditary blood disorderssuch as sickle cell anemiain

which the liver makes too much bilirubin. The mere presence of gallstones may cause more gallstones

to develop. Other factors that contribute to the formation of gallstones, particularly cholesterol stones,

include:

Sex. Women are twice as likely as men to develop gallstones. Excess estrogen from pregnancy,

hormone replacement therapy, and birth control pills appears to increase cholesterol levels in bile and

decrease gallbladder movement, which can lead to gallstones.

Family history. Gallstones often run in families, pointing to a possible genetic link.

Weight. A large clinical study showed that being even moderately overweight increases the risk for

developing gallstones. The most likely reason is that the amount of bile salts in bile is reduced, resulting

in more cholesterol. Increased cholesterol reduces gallbladder emptying. Obesity is a major risk factor

for gallstones, especially in women.

Diet. Diets high in fat and cholesterol and low in fiber increase the risk of gallstones due to increased

cholesterol in the bile and reduced gallbladder emptying.

Rapid weight loss. As the body metabolizes fat during prolonged fasting and rapid weight losssuch as

crash dietsthe liver secretes extra cholesterol into bile, which can cause gallstones. In addition, the

gallbladder does not empty properly.

Age. People older than age 60 are more likely to develop gallstones than younger people. As people

age, the body tends to secrete more cholesterol into bile.

Ethnicity. American Indians have a genetic predisposition to secrete high levels of cholesterol in bile. In

fact, they have the highest rate of gallstones in the United States. The majority of American Indian men

have gallstones by age 60. Among the Pima Indians of Arizona, 70 percent of women have gallstones by

age 30. Mexican American men and women of all ages also have high rates of gallstones.

Cholesterol-lowering drugs. Drugs that lower cholesterol levels in the blood actually increase the

amount of cholesterol secreted into bile. In turn, the risk of gallstones increases.

Diabetes. People with diabetes generally have high levels of fatty acids called triglycerides. These fatty

acids may increase the risk of gallstones.


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Diagnosis of gallstones

Ultrasound examination-- the most sensitive and specific test for gallstones. A handheld device,which a technician glides over the abdomen, sends sound waves toward the gallbladder. The

sound waves bounce off the gallbladder, liver, and other organs, and their echoes make

electrical impulses that create a picture of the gallbladder on a video monitor. If gallstones are

present, the sound waves will bounce off them, too, showing their location.

Computerized tomography (CT) scan--The CT scan is a noninvasive x ray that produces cross-section images of the body. The test may show the gallstones or complications, such as infection

and rupture of the gallbladder or bile ducts.

Cholescintigraphy (HIDA scan)--The patient is injected with a small amount of nonharmfulradioactive material that is absorbed by the gallbladder, which is then stimulated to contract.

The test is used to diagnose abnormal contraction of the gallbladder or obstruction of the bile

ducts.

Endoscopic retrograde cholangiopancreatography (ERCP)--ERCP is used to locate and removestones in the bile ducts. After lightly sedating you, the doctor inserts an endoscopea long,

flexible, lighted tube with a cameradown the throat and through the stomach and into the

small intestine. The endoscope is connected to a computer and video monitor. The doctor

guides the endoscope and injects a special dye that helps the bile ducts appear better on the

monitor. The endoscope helps the doctor locate the affected bile duct and the gallstone. The

stone is captured in a tiny basket and removed with the endoscope.

Blood tests--Blood tests may be performed to look for signs of infection, obstruction,pancreatitis, or jaundice.

TREATMENT OF GALLSTONES

Surgery

If you have gallstones without symptoms, you do not require treatment. If you are having frequent

gallbladder attacks, your doctor will likely recommend you have your gallbladder removedan

operation called a CHOLECYSTECTOMY. Surgery to remove the gallbladdera nonessential organis

one of the most common surgeries performed on adults in the United States.

Nearly all cholecystectomies are performed with laparoscopy. After giving you medication to sedate

you, the surgeon makes several tiny incisions in the abdomen and inserts a laparoscope and a miniature

video camera. The camera sends a magnified image from inside the body to a video monitor, giving the

surgeon a close-up view of the organs and tissues. While watching the monitor, the surgeon uses the

instruments to carefully separate the gallbladder from the liver, bile ducts, and other structures. Then

the surgeon cuts the cystic duct and removes the gallbladder through one of the small incisions.


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Recovery after laparoscopic surgery usually involves only one night in the hospital, and normal activity

can be resumed after a few days at home. Because the abdominal muscles are not cut during

laparoscopic surgery, patients have less pain and fewer complications than after open surgery, which

requires a 5- to 8-inch incision across the abdomen.

If tests show the gallbladder has severe inflammation, infection, or scarring from other operations, thesurgeon may perform open surgery to remove the gallbladder. In some cases, open surgery is planned;

however, sometimes these problems are discovered during the laparoscopy and the surgeon must make

a larger incision. Recovery from open surgery usually requires 3 to 5 days in the hospital and several

weeks at home. Open surgery is necessary in about 5 percent of gallbladder operations.

The most common complication in gallbladder surgery is injury to the bile ducts. An injured common bile

duct can leak bile and cause a painful and potentially dangerous infection. Mild injuries can sometimes

be treated nonsurgically. Major injury, however, is more serious and requires additional surgery.

If gallstones are present in the bile ducts, the physicianusually a gastroenterologistmay use ERCP to

locate and remove them before or during gallbladder surgery. Occasionally, a person who has had a

cholecystectomy is diagnosed with a gallstone in the bile ducts weeks, months, or even years after the

surgery. The ERCP procedure is usually successful in removing the stone in these cases.

Nonsurgical Treatment

Nonsurgical approaches are used only in special situationssuch as when a patient has a serious

medical condition preventing surgeryand only for cholesterol stones. Stones commonly recur within 5

years in patients treated nonsurgically.

Oral dissolution therapy-- Drugs made from bile acid are used to dissolve gallstones. The drugsursodiol (Actigall) and chenodiol (Chenix) work best for small cholesterol stones. Months or

years of treatment may be necessary before all the stones dissolve. Both drugs may cause mild

diarrhea, and chenodiol may temporarily raise levels of blood cholesterol and the liver enzyme

transaminase.

Contact dissolution therapy.--This experimental procedure involves injecting a drug directly intothe gallbladder to dissolve cholesterol stones. The drugmethyl tert-butyl ethercan dissolve

some stones in 1 to 3 days, but it causes irritation and some complications have been reported.

The procedure is being tested in symptomatic patients with small stones.


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Cholecystectomy

PANCREATIC CANCER

The pancreas has two main types of cells, exocrine and endocrine. Each type can form different

malignancies or benign tumors. In addition, tumors can spread to the pancreas from other organs.

Advanced technology has helped physicians recognize more cystic tumors of the pancreas. Although

many tumors are benign, one cystic tumor the intraductal papillary mucinous neoplasm is

premalignant and warrants aggressive treatment.

Exocrine Cell Tumors

Pancreatic exocrine cells typically form adenocarcinomas, malignancies that start in the ducts of thepancreas. About 95 percent of pancreatic cancers develop from exocrine cells and are

adenocarcinomas. Other less common types of exocrine cell cancers include:

Mucinous noncystic carcinoma Adenosquamous carcinomas Mucinous cyst adenocarcinoma Intraductal papillary mucinous carcinoma

Physicians base treatment plans for exocrine pancreatic cancer on how far the cancer has spread,

rather than its exact type. Benign tumors of the exocrine cells are called cystadenomas.

Endocrine Cell Tumors

Tumors that form from endocrine cells of the pancreas are less common and more likely to be benign

than exocrine cell tumors. Known as neuroendocrine tumors or islet cell tumors, their name is based on

the hormone that they produce. Tumors that develop from endocrine cells that are not hormonally

active are called nonfunctioning islet tumors.


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SYMPTOMS OF PANCREATIC CANCER

Pancreatic cancer typically does not exhibit noticeable symptoms early in its development. The most

classic symptom is that of painless jaundice, which occurs because the tumor obstructs the bile duct

and causes yellow eyes and dark urine.

Pancreatic cancer symptoms can include:

Abdominal pressure Abdominal pain Yellowing of the eyes and skin Dark urine

As the cancer spreads, some people experience pain in the upper abdomen and back. Activities such as

eating or lying down may cause increased pain. Nausea, loss of appetite, weight loss and the onset of

diabetes may also be signs of pancreatic cancer.

One form of pancreatic cancer, islet cell cancer, can cause the pancreas to make excess insulin or other

hormones. Weakness, dizziness, chills, muscle spasms or diarrhea may result.

RISK FACTORS FOR PANCREATIC CANCER

Age (particularly over 60) Male sex (likeliness of up to 30% over females) Smoking. Cigarette smoking has a risk ratio of 1.74 with regard to pancreatic cancer; a decade of

nonsmoking after heavy smoking is associated with a risk ratio of 1.2.

Diets low in vegetables and fruits Diets high in red meat Diets high in sugar-sweetened drinks (soft drinks) risk ratio 1.87. In particular, common soft

drink sweetener fructose has been linked to growth of pancreatic cancer cells.

Obesity Diabetes mellitus is both risk factor for pancreatic cancer, and, as noted earlier, new onset

diabetes can be an early sign of the disease.

Chronic pancreatitis has been linked, but is not known to be causal. The risk of pancreatic cancerin individuals with familial pancreatitis is particularly high.

Helicobacter pylori infection Family history, 510% of pancreatic cancer patients have a family history of pancreatic cancer.

The genes responsible for most of this clustering in families have yet to be identified. Pancreatic

cancer has been associated with the following syndromes; autosomal recessive ataxia-

telangiectasia and autosomal dominantly inherited mutations in the BRCA2 gene and PALB2

gene, Peutz-Jeghers syndrome due to mutations in the STK11 tumor suppressor gene,

hereditary non-polyposis colon cancer (Lynch syndrome), familial adenomatous polyposis, and


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the familial atypical multiple mole melanoma-pancreatic cancer syndrome (FAMMM-PC) due to

mutations in the CDKN2A tumor suppressor gene.

Gingivitis or periodontal disease Alcoholism

DIAGNOSIS OF PANCREATIC CANCER

Effective treatment for pancreatic cancer depends on knowing whether the tumor is confined to the

pancreas or has spread to nearby organs, nerves or blood vessels.

Computed tomography (CT) scansMuch like high-definition TVs, the scanners produce exceptionally clear, sharp images throughout the

body with 33 percent greater detail than traditional scans. The improved imaging allows doctors to

diagnose disease earlier and with greater accuracy. More importantly, scan radiation can be reduced up

to 50 percent, a critical benefit for cancer patients.

Magnetic resonance cholangiopancreatography (MRCP)

in magnetic resonance colangiopancreatography (MRCP), which uses magnetic fields and radio waves to

produce detailed images of your pancreas, liver and bile ducts. This noninvasive test is especially helpful

for diagnosing bile duct obstructions and for detecting pancreatic cysts fluid-filled pockets that can

develop on or within the pancreas. Most cysts are benign, but some may become cancerous over time

and should be followed by physicians skilled in their management.

Endoscopic ultrasound (EUS)During the test, a tiny ultrasound probe is placed in your stomach through an endoscope. The probe

produces sound waves that create extremely detailed images of your pancreas, which lies next to the

stomach.

Digital analysis of these images can help distinguish cancer from chronic pancreatitis an ongoing

inflammation of the pancreas. During EUS, your doctor may also remove cellular material (fine needle

aspiration) or small samples of pancreatic tissue (core biopsy). Mayo is one of the few medical centers in

the world performing core biopsies of the pancreas. The biopsies can help distinguish autoimmune

pancreatitis from pancreatic cancer. Doctors can also collect pancreatic juices or fluid from

precancerous cysts for laboratory analysis. EUS can be technically demanding and produces the best

results when performed by an experienced endoscopist.

Endoscopic retrograde cholangiopancreatography (ERCP)ERCP is used to both assess and treat problems in the bile ducts. During a traditional ERCP, doctors injecta dye into the biliary tract through an endoscope before taking a series of X-rays. Traditional ERCP

doesn't allow direct observation of the ducts, however, and because X-rays may not provide enough

information for a complete diagnosis, some people may need repeat procedures.


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Treatment of pancreatic cancer

The rapid and aggressive spread of pancreas cancer into surrounding tissue, its resistance to standard

chemotherapy and its tendency to recur make it one of the most challenging cancers to treat. Surgery,

radiation, and palliative care may each be needed. For many people, managing symptoms is also a

critical part of care. The most appropriate options for you depend on the location and extent of the

cancer, your age, overall health and personal wishes.

Surgery

Surgery is the best option for people whose cancer can be safely and effectively removed. This usually

means that the tumor hasn't grown into any of the major blood vessels located near the pancreas or

spread to the liver, abdominal cavity or lungs.

Unfortunately, only about 20 percent of pancreatic cancer patients have tumors that can be surgically

removed (resected). And although improvements in diagnosis, staging, surgical techniques andpostoperative care have led to much better outcomes after surgery, pancreatic resection is still one of

the most difficult and demanding operations for both surgeons and patients.

1) Whipple procedure. Also known as pancreatoduodenectomy, the Whipple procedure is themost common surgery for pancreatic cancer. The surgery involves removing the "head" of the

pancreas the wide part of the pancreas next to the duodenum, the first part of the small

intestine.

To do that, surgeons must remove the duodenum, the gallbladder, the end of the common bile

duct and sometimes part of the stomach. The intestine, bile duct and remaining part of thepancreas are then reconnected. One not uncommon complication of this surgery is leaking of

pancreatic juices from the suture line. The leaking usually stops over time with no additional

treatment. Weight loss is another frequent complication of the Whipple procedure. On average,

patients lose about 7 percent of their pre-operative bodyweight after surgery. Because the

pancreas contains insulin-producing cells, diabetes is also a potential complication. Yet most

people who have normal blood sugar before surgery don't develop diabetes and those with

recently developed diabetes actually improve after surgery. In general, although many people

do very well after the Whipple procedure, up to a third may develop immediate complications

that affect their quality of life.

After pancreatic surgery, it will take some time before you can eat normally, and you may need

long-term treatment with pancreatic enzymes to help you digest food properly. Pancreatic

enzymes, nutrition counseling and supportive care are an integral part comprehensive

pancreatic cancer treatment.


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2) Minimally invasive surgery. In select cases, the Whipple procedure can be performed using aminimally invasive (laparoscopic) procedure. Although very successful in the right hands, this

technique requires great skill because the surgery is performed through a few small incisions

rather than a single large incision.

3) Central pancreatectomy--- which removes the center portion or body of the pancreas, whileretaining both ends (the head and tail). This procedure is performed in very few medical centers

in the United States and is generally used for early-stage benign tumors in the neck of the

pancreas a difficult area to treat without removing a large portion of the gland. By preserving

more of the pancreas and thus more of the cells that produce insulin and digestive enzymes

central pancreatectomy reduces the risk of diabetes and severe digestive problems.

4) total pancreatectomy, which removes the entire pancreas, along with the gallbladder, part ofthe stomach and small intestine, the bile duct, spleen, and nearby lymph nodes; and distal

pancreatectomy, in which the body and tail of the pancreas are removed.

Radiation therapy and multi-modality therapies

Radiation can be even be delivered during surgery using intraoperative radiation electron therapy,

Intraoperative radiation electron therapy allows doctors to treat tumors with high doses of radiation

the equivalent, in some cases, of 10 to 20 daily radiation treatments without harming nearby organs.

Palliative care

When cancer is so advanced that treatment options are limited, an experienced, integrated team of

palliative care providers serves the social, psychological and spiritual needs of patients and their

families. Your care team may include physicians from a number of fields as well as dietitians, medical

social workers, chaplains, psychologists, pharmacists and pain management specialists.


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PRIMARY BILIARY CIRRHOSIS

Definition

Primary biliary cirrhosis is a disease in which the bile ducts in your liver are slowly destroyed. Bile, a fluid

produced in your liver, is essential for the proper digestion of fats. It also helps rid your body of worn-out red blood cells, cholesterol and toxins. In primary biliary cirrhosis, the destruction of your bile ducts

can cause harmful substances to build up in your liver and sometimes lead to irreversible scarring of

liver tissue (cirrhosis).

The cause of primary biliary cirrhosis remains unclear. Many experts consider primary biliary cirrhosis

an autoimmune disease in which the body turns against its own cells, although it's likely that genetic and

environmental factors also play a part. Primary

biliary cirrhosis develops slowly. Medication

can slow the progression of the disease,

especially if treatment begins early.

SYMPTOMS

Early stage

Although some people with primary biliary

cirrhosis remain symptom-free for years after

they're diagnosed, others experience a number

of symptoms early in the disease:

Fatigue. A common symptom ofprimary biliary cirrhosis is fatigue, but

doctors haven't found any correlationbetween the degree of exhaustion and

the severity of the illness. This means that people with mild primary biliary cirrhosis and those

with more serious disease may be equally fatigued.

Itching. Another common symptom, itching (pruritus), is often most bothersome over your legs,arms and back. The severity of itching may change, often becoming worse at night and

improving during the day. Nighttime itching can disturb sleep, making fatigue worse and

sometimes leading to depression. The cause of this severe itching isn't clear.

Dry eyes and mouth (sicca syndrome). Sicca syndrome often occurs in people with otherautoimmune disorders. It causes inflammation in the moisture-secreting glands of the eyes and

mouth, resulting in the decreased production of tears and saliva.

Later stage

As the destruction of bile duct and liver cells progresses, other signs and symptoms may develop, such

as:

Jaundice. A common sign of advanced liver disease, jaundice turns your skin and the whites ofyour eyes yellow. The discoloration is due to high blood levels of bilirubin, a byproduct of the


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breakdown of the hemoglobin from old or damaged red blood cells. Normally, bile carries

bilirubin out of your liver so that it can be excreted from your body. But as more bile ducts are

destroyed and the flow of bile slows, bilirubin begins to build up in your blood and eventually

jaundice becomes visible in your skin and eyes.

Hyperpigmentation. Inadequate bile flow increases the production of the skin pigment melanin.This causes your skin to become darker, even in areas that aren't exposed to the sun.

Sometimes the deeper color isn't uniform, and your skin appears blotchy.

Swollen feet (edema) and abdomen (ascites). As liver damage progresses, your body begins toretain salt and fluids. At first, the excess salt and water accumulate mainly in your feet and

ankles (edema), which tend to become more swollen late in the day. In time, fluid can also

collect in your abdomen.

Cholesterol deposits (xanthomas). Your body uses bile as the main way of eliminating excesscholesterol. When disease interferes with this process, the amount of cholesterol in the blood

increases. This can lead to the formation of fatty deposits in the skin around your eyes, your

eyelids, or in the creases in your palms, soles, elbows or knees. These raised, waxy growths

usually don't appear until blood cholesterol reaches very high levels. Even then, not everyone

with primary biliary cirrhosis develops them.

Digestive problems. Because bile is essential for the digestion and absorption of fats, primarybiliary cirrhosis can cause intestinal problems. These include diarrhea and steatorrhea greasy,

bad-smelling stools that result from poor fat digestion.

CAUSES

The exact cause of primary biliary cirrhosis isn't known, but it appears to be an immune system disorder

that slowly destroys the bile ducts in your liver. Genetics and the environment also likely play a role in

this disease.

Normally, bile is excreted into canal-like spaces between your liver cells, which drain into an

interconnected series of thin tubes (ducts). The initial ducts are quite small, but become progressively

larger as they spread through your liver, much like the branches of a tree.

Origin of the condition

The problems in primary biliary cirrhosis begin with inflammation in the smallest ducts in your liver. In

time, the inflammation spreads to and destroys nearby liver cells. As these cells are destroyed, they're

replaced by scar tissue (fibrosis). Over a period of years, the combination of ongoing inflammation,

scarring and toxicity from trapped bile can lead to cirrhosis. Cirrhosis involves irreversible scarring of

liver tissue that makes it impossible for your liver to carry out essential functions.

The inflammation begins when T lymphocytes (T cells) begin accumulating in your liver. T cells are whiteblood cells that are part of your immune system response. Normally, T cells recognize and help defend

against bacteria and fungi. But in primary biliary cirrhosis, the T cells invade and destroy the cells lining

the small bile ducts. The T cells also produce chemicals that stimulate liver cells to secrete proteins that

attract more T cells, thereby creating an ongoing cycle of damage.

Researchers suspect that a genetic susceptibility coupled with an environmental trigger, such as

infection, may be at the root of this abnormal immune response:


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Genetics--Primary biliary cirrhosis seems to run in families, and scientists believe that some people may

inherit certain immune system defects that make them more susceptible to the disorder. Research has

identified three genetic variations associated with primary biliary cirrhosis. This finding may eventually

help researchers narrow in on the cause of primary biliary cirrhosis.

Infection--For decades, researchers have suspected that primary biliary cirrhosis might result from a

bacterial, fungal or parasitic infection, which would explain the massing of T cells in the small bile ducts.

Some women reported having urinary tract infections, primarily those caused by the Escherichia coli

bacterium, prior to the development of primary biliary cirrhosis. However, no commonplace infections

have yet been consistently linked to primary biliary cirrhosis.

RISK FACTORS

The following factors may increase your risk of primary biliary cirrhosis:

Your sex. More than 90 percent of people with primary biliary cirrhosis are women. Your age. Most people diagnosed with primary biliary cirrhosis are 35 to 60 years old. Although

older adults can develop the disease, it's rare in children.

Family history. Having a family history of primary biliary cirrhosis increases your risk ofdeveloping the disease.

COMPLICATIONS

As liver damage progresses, people with primary biliary cirrhosis may develop a number of serious

problems, including:

Cirrhosis. The term "primary biliary cirrhosis" isn't entirely accurate because cirrhosis develops only in

the later stages of the disease often many years after diagnosis. Yet when it does occur, cirrhosis can

be life-threatening because it interferes with your liver's ability to carry out essential functions. Cases ofprimary biliary cirrhosis are divided into four stages. The first stage inflammation of the bile ducts

is the least serious, and stage 4 cirrhosis the most serious. Ongoing cirrhosis can lead to liver

failure, which occurs when your liver is no longer able to function.

Increased pressure in the portal vein (portal hypertension). Blood from your intestine, spleen and

pancreas enters your liver through a large blood vessel called the portal vein. When scar tissue blocks

normal circulation through your liver, blood backs up, much like water behind a dam, leading to

increased pressure within the vein. And because blood doesn't flow normally through your liver,

hormones, drugs and other toxins aren't filtered properly before entering your bloodstream.

Enlarged veins (varices). When circulation through the portal vein is slowed or blocked, blood may backup into other veins mainly those in your stomach and esophagus. The blood vessels are thin walled,

and increased pressure in your veins can cause bleeding in your upper stomach or esophagus. This

bleeding is a life-threatening emergency that requires immediate medical care.

Liver cancer. The destruction of healthy liver tissue that occurs in cirrhosis increases your risk of liver

cancer.


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Weak bones (osteoporosis) . Liver scarring interferes with your liver's ability to process vitamin D and

calcium, both of which are essential for bone growth and health. As a result, weak, brittle bones and

bone loss may be complications of late-stage primary biliary cirrhosis, and your doctor may order a bone

density test to look for osteoporosis.

Vitamin deficiencies. A lack of bile affects the absorption of fats and of the fat-soluble vitamins, A, D, E

and K. This sometimes leads to deficiencies of these vitamins in advanced cases of primary biliary

cirrhosis.

Cognitive impairment. Some people with primary biliary cirrhosis have problems with memory and

concentration. Cognitive difficulties don't seem to correlate directly to the amount of liver damage,

however.

Other complications

In addition to bile duct and liver damage, people with primary biliary cirrhosis are likely to have other

metabolic or immune system disorders, including:

Thyroid disease. Thyroid problems are common in people with primary biliary cirrhosis. They may

appear long before bile duct damage is diagnosed, or thyroid disorders may develop after you've

received a diagnosis of primary biliary cirrhosis.

Limited scleroderma (CREST syndrome). This immune system disorder is a subset of scleroderma, a

disease that leads to thickening, tightening and hardening of connective tissue. CREST syndrome can

affect many body systems, including your blood vessels and esophagus, and sometimes your digestive

tract, lungs and heart. People with primary biliary cirrhosis generally have some, rather than all, of the

signs and symptoms of CREST.

Raynaud's phenomenon. One of the components of CREST, Raynaud's phenomenon may also occur inpeople with primary biliary cirrhosis. It occurs when small blood vessels (capillaries) spasm in response

to cold or emotional stress, blocking the flow of blood. The areas of affected skin generally turn white

before becoming blue, cold and numb. When circulation improves, the skin usually reddens and may

throb or tingle.

Rheumatoid arthritis. Some people with primary biliary cirrhosis have the aching joints that typify

rheumatoid arthritis, another autoimmune disorder.

TESTS AND DIAGNOSIS

Many people with primary biliary cirrhosis have no symptoms of the disease when they're initiallydiagnosed. Instead, doctors often become aware of a problem during routine blood tests or an

evaluation for another condition.

If your doctor suspects primary biliary cirrhosis, several tests can help make the diagnosis, including:

Liver function tests. These blood tests check the levels of enzymes that may indicate liverdisease in general and bile duct injury in particular. Certain liver enzymes are elevated in most


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people with primary biliary cirrhosis, especially alkaline phosphatase, which is produced in the

bile ducts.

Ultrasound imaging. This noninvasive test uses high-frequency sound waves to create preciseimages of structures within the body, including the bile ducts. It's sometimes used to rule out

other causes of bile flow blockage, such as gallstones or tumors.

Anti-mitochondrial antibodies (AMAs). Found in every cell, mitochondria are the prime energyproducers of your body. Antibodies are proteins in your blood that help destroy bacteria and

other harmful pathogens. Most people with primary biliary cirrhosis have anti-mitochondrial

antibodies antibodies that target enzymes in the mitochondria. These antibodies almost

never occur in people who don't have primary biliary cirrhosis, even if they have other liver

disorders. For that reason, a positive AMA test is considered a very reliable indicator of the

disease. At the same time, a small percentage of people with primary biliary cirrhosis don't have

AMAs. False-positive tests, which indicate a problem where none exists, also can occur. Because

an AMA test isn't entirely foolproof, doctors usually perform a liver biopsy, which can

definitively confirm the presence or absence of the disease.

Liver biopsy. In this test, a small sample of liver tissue (biopsy) is removed and examined in alaboratory, either to confirm the diagnosis or to determine the extent (stage) of the disease.

Doctors withdraw the tissue through a small incision using a thin needle. Doctors may take moreliver biopsies as time goes on to check the progression of the disease.

Magnetic resonance imaging (MRI) and magnetic resonance elastography (MRE). MRI is afrequently used imaging test that uses a powerful magnetic field and radio waves to produce

detailed images inside your body. When diagnosing primary biliary cirrhosis, MRI can be used to

detect abnormalities of your liver. MRE is a relatively new test that may help your doctor

diagnose primary biliary cirrhosis and may help avoid the need for a liver biopsy, which is more

invasive. MRE technology works by combining traditional magnetic resonance imaging with low-

frequency sounds waves. The MRI component shows the size and structure of your tissues and

organs. The low-frequency sound waves then help reveal physical properties of those tissues

and organs such as tissue stiffness. Stiffness of your liver may indicate cirrhosis.

TREATMENT

Treatments aimed at slowing the disease and prolonging life include:

1) Ursodeoxycholic acid (UDCA). Also known as ursodiol (Actigall), UDCA is a bile acid that helpsmove bile through your liver. Although UDCA doesn't cure primary biliary cirrhosis, it may

prolong life if started early in the disease and is commonly considered the first line of therapy.

It's less likely to help people with advanced liver damage. Side effects of UDCA may include

weight gain, hair loss and diarrhea.

2) Other drugs. Sometimes other drugs are used off-label or in clinical trials to treat primary biliarycirrhosis, but many have proved to have serious side effects or haven't been effective. For

example, some studies show that the drug methotrexate, which is normally used to treat

arthritis, psoriasis and some types of cancer, isn't helpful in primary biliary cirrhosis, whereas

others show it to be somewhat effective.

3) Liver transplant. When treatments no longer control primary biliary cirrhosis and the liverbegins to fail, a liver transplant may help prolong life. People with primary biliary cirrhosis who

have liver transplants often do very well, although the disease may recur in the new liver.

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