Case 4

Erri Pratama
405140008

erripratama13@gmail.com
CHOLELITHIASIS
CHOLEDOCHOLITHIASIS

CHOLECYSTITIS

CHOLANGITIS
PANCREATITIS
CA PANCREAS

FATTY LIVER
CHOLELITHIASIS
(gallstone)

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BACKGROUND
Cholelithiasis is the medical term for gallstone disease. Gallstones are
concretions that form in the biliary tract, usually in the gallbladder

Douglas M Heuman, MD, FACP, FACG, AGAF Chief of Hepatology, Hunter Holmes McGuire Department of Veterans Affairs Medical Center; Professor, Department
of Internal Medicine, Division of Gastroenterology, Virginia Commonwealth University School of Medicine
 Gallstones develop insidiously,
and they may remain
asymptomatic for decades. Migration of a gallstone into
the opening of the cystic duct may block the outflow of
bile during gallbladder contraction. The resulting increase
in gallbladder wall tension produces a characteristic type
of pain (biliary colic).
Cystic duct obstruction, if it
persists for more than a few hours, may lead to acute
gallbladder inflammation (acute cholecystitis).

Choledocholithiasis refers to the presence of

one or more gallstones in the common bile
duct. Usually, this occurs when a gallstone passes from the
gallbladder into the common bile duct

Douglas M Heuman, MD, FACP, FACG, AGAF Chief of Hepatology, Hunter Holmes McGuire Department of Veterans Affairs Medical Center; Professor, Department
of Internal Medicine, Division of Gastroenterology, Virginia Commonwealth University School of Medicine
 A gallstone in the common bile duct may impact distally in the
ampulla of Vater, the point where the common bile duct and
pancreatic duct join before opening into the duodenum.
Obstruction of bile flow by a stone at this critical point may
lead to abdominal pain and jaundice. Stagnant bile above an
obstructing bile duct stone often becomes infected, and
bacteria can spread rapidly back up the ductal system
into the liver to produce a life-threatening infection called
ascending cholangitis. Obstruction of the pancreatic
duct by a gallstone in the ampulla of Vater can trigger activation
of pancreatic digestive enzymes within the pancreas itself,
leading to acute pancreatitis.
Chronically, gallstones in the gallbladder may cause progressive
fibrosis and loss of function of the gallbladder, a condition
known as chronic cholecystitis. Chronic cholecystitis predisposes
to gallbladder cancer.
Ultrasonography is the initial diagnostic procedure of choice in
most cases of suspected gallbladder or biliary tract disease

Douglas M Heuman, MD, FACP, FACG, AGAF Chief of Hepatology, Hunter Holmes McGuire Department of Veterans Affairs Medical Center; Professor, Department
of Internal Medicine, Division of Gastroenterology, Virginia Commonwealth University School of Medicine
 EPIDEMIOLOGY

Race-, sex-, and age-related demographics

Prevalence of gallstones is highest in people of northern European descent, and in Hispanic populations and Native
American populations.[6] Prevalence of gallstones is lower in Asians and African Americans.
Women are more likely to develop cholesterol gallstones than men, especially during their reproductive years, when the
incidence of gallstones in women is 2-3 times that in men. The difference appears to be attributable mainly to estrogen,
which increases biliary cholesterol secretion.[7]
Risk of developing gallstones increases with age. Gallstones are uncommon in children in the absence of congenital
anomalies or hemolytic disorders. Beginning at puberty, the concentration of cholesterol in bile increases. After age 15
years, the prevalence of gallstones in US women increases by about 1% per year; in men, the rate is less, about 0.5% per
year. Gallstones continue to form throughout adult life, and the prevalence is greatest at advanced age. The incidence in
women falls with menopause, but new stone formation in men and women continues at a rate of about 0.4% per year
until late in life.
Among individuals undergoing cholecystectomy for symptomatic cholelithiasis, 8-15% of patients younger than 60 years
have common bile duct stones, compared with 15-60% of patients older than 60 years.

Shaffer EA. Epidemiology and risk factors for gallstone disease: has the paradigm changed in the 21st century?. Curr Gastroenterol Rep. 2005 May. 7(2):132-40
Figure 1: Worldwide prevalence of gallstones in females based on ultrasonographic surveys (Stinton LM, Shaffer EA, Gut and Liver 2012,; 6: 172-187).
 PATHOPHYSIOLOGY
Gallstone formation occurs because certain substances in bile are present in concentrations that approach the
limits of their solubility. When bile is concentrated in the gallbladder, it can become supersaturated with these
The crystals are trapped in
substances, which then precipitate from the solution as microscopic crystals.
gallbladder mucus, producing gallbladder sludge. Over time, the crystals grow,
aggregate, and fuse to form macroscopic stones. Occlusion of the ducts by sludge
and/or stones produces the complications of gallstone disease.

The 2 main substances involved in gallstone formation are cholesterol and calcium bilirubinate.

Douglas M Heuman, MD, FACP, FACG, AGAF Chief of Hepatology, Hunter Holmes McGuire Department of Veterans Affairs Medical Center; Professor, Department
of Internal Medicine, Division of Gastroenterology, Virginia Commonwealth University School of Medicine
Cholesterol gallstones
More than 80% of gallstones in the United States contain cholesterol as their major component. Liver cells secrete
cholesterol into bile along with phospholipid (lecithin) in the form of small spherical membranous bubbles, termed
unilamellar vesicles. Liver cells also secrete bile salts, which are powerful detergents required for the digestion and
absorption of dietary fats.
Bile salts in bile dissolve the unilamellar vesicles to form soluble aggregates called mixed micelles. This happens mainly in
the gallbladder, where bile is concentrated by reabsorption of electrolytes and water.
Compared with vesicles (which can hold up to 1 molecule of cholesterol for every molecule of lecithin), mixed micelles
have a lower carrying capacity for cholesterol (about 1 molecule of cholesterol for every 3 molecules of lecithin). If bile
contains a relatively high proportion of cholesterol to begin with, then as bile is concentrated, progressive dissolution of
vesicles may lead to a state in which the cholesterol-carrying capacity of the micelles and residual vesicles is exceeded. At
this point, bile is supersaturated with cholesterol, and cholesterol monohydrate crystals may form.
Thus, the main factors that determine whether cholesterol gallstones will form are (1) the amount of cholesterol
secreted by liver cells, relative to lecithin and bile salts, and (2) the degree of concentration and extent of stasis of bile
in the gallbladder.
Calcium, bilirubin, and pigment gallstones
Bilirubin, a yellow pigment derived from the breakdown of heme, is actively secreted into bile by liver cells. Most of the
bilirubin in bile is in the form of glucuronide conjugates, which are water soluble and stable, but a small proportion
consists of unconjugated bilirubin. Unconjugated bilirubin, like fatty acids, phosphate, carbonate, and other anions, tends
to form insoluble precipitates with calcium. Calcium enters bile passively along with other electrolytes.
In situations of high heme turnover, such as chronic hemolysis or cirrhosis, unconjugated bilirubin may be present in bile
at higher than normal concentrations. Calcium bilirubinate may then crystallize from the solution and eventually form
stones. Over time, various oxidations cause the bilirubin precipitates to take on a jet-black color, and stones formed in this
manner are termed black pigment gallstones. Black pigment stones represent 10-20% of gallstones in the United States.
Bile is normally sterile, but in some unusual circumstances (eg, above a biliary stricture), it may become colonized with
bacteria. The bacteria hydrolyze conjugated bilirubin, and the resulting increase in unconjugated bilirubin may lead to
precipitation of calcium bilirubinate crystals.
Bacteria also hydrolyze lecithin to release fatty acids, which also may bind calcium and precipitate from the solution. The
resulting concretions have a claylike consistency and are termed brown pigment stones. Unlike cholesterol or black
pigment gallstones, which form almost exclusively in the gallbladder, brown pigment gallstones often form de novo in the
bile ducts. Brown pigment gallstones are unusual in the United States but are fairly common in some parts of Southeast
Asia, possibly related to liver fluke infestation.
ETIOLOGY

Cholesterol gallstones, black pigment gallstones, and brown pigment gallstones have different pathogeneses and
different risk factors

Cholesterol gallstones
Cholesterol gallstones are associated with female sex, European or Native American ancestry, and
increasing age.
Other risk factors include the following:
• Obesity
• Pregnancy
• Gallbladder stasis
• Drugs
• Heredity
The metabolic syndrome of truncal obesity, insulin resistance, type II diabetes mellitus, hypertension, and
hyperlipidemia is associated with increased hepatic cholesterol secretion and is a major risk factor for the development
of cholesterol gallstones.
Cholesterol gallstones are more common in women who have experienced multiple pregnancies. A major contributing
factor is thought to be the high progesterone levels of pregnancy. Progesterone reduces gallbladder contractility, leading
to prolonged retention and greater concentration of bile in the gallbladder.

Other causes of gallbladder stasis associated with increased risk of gallstones include high spinal cord injuries, prolonged
fasting with total parenteral nutrition, and rapid weight loss associated with severe caloric and fat restriction (eg, diet,
gastric bypass surgery).

A number of medications are associated with the formation of cholesterol gallstones. Estrogens administered for
contraception or for the treatment of prostate cancer increase the risk of cholesterol gallstones by increasing biliary
cholesterol secretion. Clofibrate and other fibrate hypolipidemic drugs increase hepatic elimination of cholesterol via
biliary secretion and appear to increase the risk of cholesterol gallstones. Somatostatin analogues appear to predispose to
gallstones by decreasing gallbladder emptying.
About 25% of the predisposition to cholesterol gallstones appears to be hereditary, as judged from studies of identical and
fraternal twins. At least a dozen genes may contribute to the risk.[3] A rare syndrome of low phospholipid–associated
cholelithiasis occurs in individuals with a hereditary deficiency of the biliary transport protein required for lecithin
secretion.

Poupon R, Rosmorduc O, Boëlle PY, Chrétien Y, Corpechot C, Chazouillères O, et al. Genotype-phenotype relationships in the low-phospholipid associated
cholelithiasis syndrome. A study of 156 consecutive patients. Hepatology. 2013 Mar 26
HISTORY & CLINICAL FINDINGS

Gallstone disease may be thought of as having the following 4 stages:

1.The lithogenic state, in which conditions favor gallstone formation
2.Asymptomatic gallstones
3.Symptomatic gallstones, characterized by episodes of biliary colic
4.Complicated cholelithiasis
Symptoms and complications of gallstone disease result from effects occurring within the gallbladder or from
stones that escape the gallbladder to lodge in the common bile duct.
Asymptomatic gallstones
Gallstones may be present in the gallbladder for decades without causing symptoms or complications. In patients with
asymptomatic gallstones discovered incidentally, the likelihood of developing symptoms or complications is 1-2% per year.
In most cases, asymptomatic gallstones do not require any treatment.

Because they are common, gallstones often coexist with other gastrointestinal conditions. There is little evidence to
support a causal association between gallstones and chronic abdominal pain, heartburn, postprandial distress, bloating,
flatulence, constipation, or diarrhea.

Dyspepsia that occurs reproducibly following ingestion of fatty foods is often wrongly attributed to gallstones, when
irritable bowel syndrome or gastroesophageal reflux is the true culprit. Gallstones discovered during an evaluation for
nonspecific symptoms are usually innocent bystanders, and treatment directed at the gallstones is unlikely to relieve these
symptoms.
 Biliary colic
Pain termed biliary colic occurs when gallstones or sludge fortuitously impact in the cystic duct during a gallbladder
contraction, increasing gallbladder wall tension. In most cases, the pain resolves over 30 to 90 minutes as the
gallbladder relaxes and the obstruction is relieved.
Episodes of biliary colic are sporadic and unpredictable. The patient localizes the pain to the epigastrium or right upper
quadrant and may describe radiation to the right scapular tip (Collins sign[9] ). The pain begins postprandially (usually
within an hour after a fatty meal), is often described as intense and dull, and may last from 1-5 hours. From onset, the
pain increases steadily over about 10 to 20 minutes and then gradually wanes when the gallbladder stops contracting
and the stone falls back into the gallbladder. The pain is constant in nature and is not relieved by emesis, antacids,
defecation, flatus, or positional changes. It may be accompanied by diaphoresis, nausea, and vomiting.
Other symptoms, often associated with cholelithiasis, include indigestion, dyspepsia, belching, bloating, and fat
intolerance. However, these are very nonspecific and occur in similar frequencies in individuals with and without
gallstones; cholecystectomy has not been shown to improve these symptoms.

Gilani SN, Bass G, Leader F, Walsh TN. Collins' sign: validation of a clinical sign in cholelithiasis. Ir J Med Sci. 2009 Aug 14.
Complications of gallbladder stones
Acute cholecystitis occurs when persistent stone impaction in the cystic duct causes the gallbladder to become
distended and progressively inflamed. Patients experience the pain of biliary colic, but, instead of resolving
spontaneously, the pain persists and worsens.

Overgrowth of colonizing bacteria in the gallbladder often occurs, and, in severe cases, accumulation of pus in the
gallbladder, termed gallbladder empyema, occurs. The gallbladder wall may become necrotic, resulting in perforation
and pericholecystic abscess. Acute cholecystitis is considered a surgical emergency, although pain and inflammation
may subside with conservative measures, such as hydration and antibiotics.

Chronically, gallstones may cause progressive fibrosis of the gallbladder wall and loss of gallbladder function, termed
chronic cholecystitis. The pathogenesis of this complication is not completely understood. Repeated attacks of acute
cholecystitis may play a role, as may localized ischemia produced by pressure of stones against the gallbladder wall.
The chronically fibrotic gallbladder may become shrunken and adherent to the adjacent viscera.

Gallbladder adenocarcinoma is an uncommon cancer that usually develops in the setting of gallstones and chronic
cholecystitis. Gallbladder cancers commonly invade the adjacent liver and common bile duct, producing jaundice. The
prognosis is poor unless the cancer is localized to the gallbladder, in which case cholecystectomy may be curative.
Complications of stones in the common bile duct

Gallstones are initially retained in the gallbladder by the spiral valves of the cystic duct. Following episodes of gallstone
impaction in the cystic duct, these valves may become obliterated and stones may pass into the common bile duct. Patients
who have passed one stone tend to pass more stones over the subsequent months.
Stones in the common bile duct may be asymptomatic, but, more commonly, they impact distally in the ampulla of Vater.
This may produce biliary colic indistinguishable from that caused by cystic duct stones. Because impaction of common bile
duct stones occludes the flow of bile from the liver to the intestine, pressure rises in the intrahepatic bile ducts, leading to
elevation of liver enzymes and jaundice.
Bacterial overgrowth in stagnant bile above an obstructing common duct stone produces purulent inflammation of the liver
and biliary tree, termed ascending cholangitis. Characteristic features include the Charcot triad of fever, jaundice, and right
upper quadrant pain. Patients may rapidly develop septic shock unless the ductal obstruction is relieved.
Other complications
Inflammation from chronic cholelithiasis may result in fusion of the gallbladder to the extrahepatic biliary tree,
causing Mirizzi syndrome. Alternatively, a fistula into the intestinal tract may form, causing gallstone ileus
Approach Considerations
The treatment of gallstones depends upon the stage of disease. Ideally, interventions in the lithogenic state could prevent
gallstone formation, although, currently, this option is limited to a few special circumstances. Asymptomatic gallstones
may be managed expectantly.
Once gallstones become symptomatic, definitive surgical intervention with cholecystectomy is usually indicated, although,
in some cases, medical dissolution may be considered. In uncomplicated cholelithiasis with biliary colic, medical
management may be a useful alternative to cholecystectomy in selected patients, particularly those in whom surgery
would pose a high risk. Medical treatment, beyond pain control, is not initiated in the emergency department.
Medical treatments for gallstones, used alone or in combination, include the following:
•Oral bile salt therapy (ursodeoxycholic acid)
•Contact dissolution
•Extracorporeal shockwave lithotripsy
Medical management is more effective in patients with good gallbladder function who have small stones (< 1 cm) with a
high cholesterol content. Bile salt therapy may be required for more than 6 months and has a success rate less than 50%.
Treatment of Asymptomatic Gallstones

Surgical treatment of asymptomatic gallstones without medically complicating diseases is discouraged. The risk of
complications arising from interventions is higher than the risk of symptomatic disease. Approximately 25% of patients with
asymptomatic gallstones develop symptoms within 10 years.
Persons with diabetes and women who are pregnant should have close follow-up to determine if they become symptomatic
or develop complications.
However, cholecystectomy for asymptomatic gallstones may be indicated in the following patients:
• Patients with large gallstones, greater than 2 cm in diameter
• Patients with nonfunctional or calcified (porcelain) gallbladder observed on imaging studies and who are at high risk of
gallbladder carcinoma
• Patients with spinal cord injuries or sensory neuropathies affecting the abdomen
• Patients with sickle cell anemia in whom the distinction between painful crisis and cholecystitis may be difficult
Medical dissolution of gallstones
Ursodeoxycholic acid (ursodiol) is a gallstone dissolution agent. In humans, long-term administration of ursodeoxycholic acid
reduces cholesterol saturation of bile, both by reducing liver cholesterol secretion and by reducing the detergent effect of bile
salts in the gallbladder (thereby preserving vesicles that have a high cholesterol carrying capacity). Desaturation of bile
prevents crystals from forming and, in fact, may allow gradual extraction of cholesterol from existing stones.
Treatment of Patients with Symptomatic Gallstones
In patients with symptomatic gallstones, discuss the options for surgical and nonsurgical intervention; emergency
physicians should refer patients to their primary care provider and obtain surgical consultant for outpatient follow-
up.

Cholecystectomy
Removal of the gallbladder (cholecystectomy) is generally indicated in patients who have experienced symptoms or
complications of gallstones, unless the patient's age and general health make the risk of surgery prohibitive. In some
cases of gallbladder empyema, temporary drainage of pus from the gallbladder (cholecystostomy) may be preferred
to allow stabilization and to permit later cholecystectomy under elective circumstances.
In patients with gallbladder stones who are suspected to have concurrent common bile duct stones, the surgeon can
perform intraoperative cholangiography at the time of cholecystectomy. The common bile duct can be explored
using a choledochoscope. If common duct stones are found, they can usually be extracted intraoperatively.
Alternatively, the surgeon can create a fistula between the distal bile duct and the adjacent duodenum
(choledochoduodenostomy), allowing stones to pass harmlessly into the intestine.
Cholecystostomy
In patients who are critically ill with gallbladder empyema and sepsis, cholecystectomy can be treacherous. In this circumstance
the surgeon may elect to perform cholecystostomy, a minimal procedure involving placement of a drainage tube in th
gallbladder. This usually results in clinical improvement. Once the patient stabilizes, definitive cholecystectomy can b
performed under elective circumstances.
Cholecystostomy also can be performed in some cases by invasive radiologists under CT-scan guidance. This approac
eliminates the need for anesthesia and is especially appealing in a patient who is clinically unstable.
Endoscopic sphincterotomy
If surgical removal of common bile duct stones is not immediately feasible, endoscopic retrograde sphincterotomy can
be used. In this procedure, the endoscopist cannulates the bile duct via the papilla of Vater. Using an electrocautery
sphincterotome, the endoscopist makes an incision measuring approximately 1 cm through the sphincter of Oddi and
the intraduodenal portion of the common bile duct, creating an opening through which stones can be extracted.
Endoscopic retrograde sphincterotomy is especially useful in patients who are critically ill with ascending cholangitis
caused by impaction of a gallstone in the ampulla of Vater. Other indications for the procedure are as follows:
•Removal of common bile duct stones inadvertently left behind during previous cholecystectomy
•Preoperative clearing of stones from the common bile duct to eliminate the need for intraoperative common bile duct
exploration, especially in situations where the surgeon's expertise in laparoscopic bile duct exploration is limited or the
patient's anesthesia risk is high
•Preventing recurrence of acute gallstone pancreatitis or other complications of choledocholithiasis in patients who are
too sick to undergo elective cholecystectomy or whose long-term prognosis is poor
Intraoperative endoscopic sphincterotomy (IOES) during laparoscopic cholecystectomy has been suggested as an
alternative treatment to preoperative endoscopic sphincterotomy (POES) followed by laparoscopic cholecystectomy;
this is because IOES is as effective and safe as POES and results in a significantly shorter hospital stay.

Gurusamy K, Sahay SJ, Burroughs AK, Davidson BR. Systematic review and meta-analysis of intraoperative versus preoperative endoscopic sphincterotomy in patients with
gallbladder and suspected common bile duct stones. Br J Surg. 2011 Jul. 98(7):908-16.
Prevention of Gallstones
Ursodeoxycholic acid treatment can prevent gallstone formation. This has been demonstrated in the setting of rapid
weight loss caused by very low-calorie diets or by bariatric surgery, which are associated with a high risk of new
cholesterol gallstones (20-30% within 4 mo). Administration of ursodeoxycholic acid at a dose of 600 mg daily for 16
weeks reduces the incidence of gallstones by 80% in this setting.
Recommending dietary changes of decreased fat intake is prudent; this may decrease the incidence of biliary colic
attacks. However, it has not been shown to cause dissolution of stones.
 Diet and Activity
Little evidence suggests that dietary composition affects the natural history of gallstone disease in humans. Obese
patients who undertake aggressive weight-loss programs or undergo bariatric surgery are at risk to develop gallstones;
short-term prophylaxis with ursodeoxycholic acid should be considered.
Coffee consumption appears to be associated with a reduced risk of gallstone disease.

Zhang YP, Li WQ, Sun YL, Zhu RT, Wang WJ. Systematic review with meta-analysis: coffee consumption and the risk of gallstone
disease. Aliment Pharmacol Ther. 2015 Sep. 42 (6):637-48.
PROGNOSIS
Less than half of patients with gallstones become symptomatic. The mortality rate for an elective cholecystectomy is 0.5%
with less than 10% morbidity. The mortality rate for an emergent cholecystectomy is 3-5% with 30-50% morbidity.
Following cholecystectomy, stones may recur in the bile duct. Separately, single-incisional laparoscopic cholecystectomy
appears to be associated with an incisional hernia rate of 8%, with age (≥50 years) and body mass index (BMI) (≥30
kg/m2) as independent predictive factors.[8]
Approximately 10-15% of patients have an associated choledocholithiasis. The prognosis in patients with
choledocholithiasis depends on the presence and severity of complications. Of all patients who refuse surgery or are unfit
to undergo surgery, 45% remain asymptomatic from choledocholithiasis, while 55% experience varying degrees of
complications.
CHOLEDOCHOLITHIASIS
(gallstone in common bile duct)

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Common bile duct stone, also known as choledocholithiasis, is the presence of gallstones in the
common bile duct (thus choledocho- + lithiasis). This condition causes jaundice and liver cell damage, and
requires treatment by cholecystectomy and/or ERCP.

National Institute of Diabetes and Digestive and Kidney Diseases (2007). "Gallstones" (PDF). Bethesda, Maryland:
National Digestive Diseases Information Clearinghouse, National Institutes of Health, United States Department of
Health and Human Services. Retrieved 2010-11-06.
Signs and symptoms
Murphy's sign is commonly negative on physical examination in choledocholithiasis,
helping to distinguish it from cholecystitis. Jaundice of the skin or eyes is an important physical finding in
biliary obstruction. Jaundice and/or clay-colored stool may raise suspicion of choledocholithiasis or even gallstone
pancreatitis. If the above symptoms coincide with fever and chills, the diagnosis of ascending cholangitis may also be
considered.

Greater than 70% of people with gallstones are asymptomatic and are found incidentally on ultrasound.
Studies have shown that 10% of those people will develop symptoms within five years of diagnosis and
20% within 20 years.
Causes

While stones can frequently pass through the common bile duct (CBD) into the
duodenum, some stones may be too large to pass through the CBD and may cause an
obstruction. One risk factor for this is duodenal diverticulum.
Pathophysiology
This obstruction may lead to jaundice, elevation in alkaline
phosphatase, increase in conjugated bilirubin in the blood and
increase in cholesterol in the blood. It can also cause acute
pancreatitis and ascending cholangitis.
Diagnosis
Choledocholithiasis (stones in common bile duct) is one of the complications of cholelithiasis (gallstones), so the
initial step is to confirm the diagnosis of cholelithiasis. Patients with cholelithiasis typically present with pain in the
right-upper quadrant of the abdomen with the associated symptoms of nausea and vomiting, especially after a fatty
meal. The physician can confirm the diagnosis of cholelithiasis with an abdominal ultrasound that shows the
ultrasonic shadows of the stones in the gallbladder.
The diagnosis of choledocholithiasis is suggested when the liver function blood test shows an elevation in bilirubin
and serum transaminases. Other indicators include raised indicators of ampulla of vater (pancreatic duct
obstruction) such as lipases and amylases. In prolonged cases the INR may change due to a decrease in vitamin
K absorption. (It is the decreased bile flow which reduces fat breakdown and therefore absorption of fat soluble
vitamins). The diagnosis is confirmed with either an MRCP (magnetic resonance cholangiopancreatography), an
ERCP, or an intraoperative cholangiogram. If the patient must have the gallbladder removed for gallstones, the
surgeon may choose to proceed with the surgery, and obtain a cholangiogram during the surgery. If the
cholangiogram shows a stone in the bile duct, the surgeon may attempt to treat the problem by flushing the stone
into the intestine or retrieve the stone back through the cystic duct.
On a different pathway, the physician may choose to proceed with ERCP before surgery. The benefit of ERCP is
that it can be utilized not just to diagnose, but also to treat the problem. During ERCP the endoscopist may
surgically widen the opening into the bile duct and remove the stone through that opening. ERCP, however, is an
invasive procedure and has its own potential complications. Thus, if the suspicion is low, the physician may choose
to confirm the diagnosis with MRCP, a non-invasive imaging technique, before proceeding with ERCP or surgery.
Treatment
Treatment involves an operation called a choledocholithotomy, which is the removal of the gallstone from the
bile duct using ERCP, although surgeons are now increasingly using laparoscopy with cholangiography. In this
procedure, tiny incisions are made in the abdomen and then in the cystic duct that connects the gallbladder to the
bile duct, and a thin tube is introduced to perform a cholangiography. If stones are identified, the surgeon inserts a
tube with an inflatable balloon to widen the duct and the stones are usually removed using either a balloon or tiny
basket.

If laparoscopy is unsuccessful, an open choledocholithotomy is performed. This procedure may be used in the case of
large stones, when the duct anatomy is complex, during or after some gallbladder operations when stones are
detected, or when ERCP or laparoscopic procedures are not available.

Typically, the gallbladder is then removed, an operation called cholecystectomy, to prevent a future occurrence of
common bile duct obstruction or other complications.

Open or Laparoscopic Common Bile Duct Exploration (Choledocholithotomy)". The New York Times Health Guide. The New
York Times Company. 26 Aug 2013. Retrieved 17 April 2
 Cholecystectomy
What Is It?
Cholecystectomy is the surgical removal of the gallbladder, the
small saclike organ located near the liver in the upper right side
of the abdomen. It is attached to the main duct that carries
bile from the liver into the intestine. Bile helps your body to
break down and absorb fats. The gallbladder temporarily
stores bile from the liver. When you eat, the gallbladder
contracts, and squeezes extra bile into the intestine to aid
digestion.

There are two ways to remove the gallbladder:

•Traditional surgery – The surgeon cuts open the abdomen

and removes the gallbladder through an incision that is about
6 inches long. The abdomen is then stitched closed again.

https://www.drugs.com/health-guide/cholecystectomy.html
 Laparoscopic surgery – The surgeon makes four small (less
than an inch) incisions for a laparoscope and instruments. A
laparoscope is a tube-like instrument with a camera for
viewing, and with it the surgeon can to guide the surgical
The gallbladder
instruments to remove the gallbladder.
is cut away from the liver and the bile duct and
removed through one of the small incisions.

https://www.drugs.com/health-guide/cholecystectomy.html
 What It's Used For
Surgeons remove gallbladders to prevent complications from gallstones, which are rocklike lumps that form inside
the gallbladder. Gallstones can cause symptoms as simple as intermittent crampy pain after eating, but they also can
lead to cholecystitis, cholangitis, or pancreatitis. Cholecystitis is an inflammation or infection of the gallbladder that
develops when a gallstone blocks the bile duct (or tube) that leads from the gallbladder to the main bile duct.
Cholecystitis causes fever, nausea or vomiting, and pain in the upper right side of the abdomen. Cholangitis is an
infection of the bile ducts that may occur when a gallstone passes out of the gallbladder and blocks the main bile
duct between the liver and intestine. Pancreatitis is an inflammation of the pancreas that can be caused by a
gallstone blocking the duct coming from the pancreas (this pancreatic duct is attached to the bile duct). This leads to
pancreatic enzymes irritating and inflaming the pancreas. Cholecystitis is not usually a severe problem, but
cholangitis and pancreatitis can be.

https://www.drugs.com/health-guide/cholecystectomy.html
 Preparation
Your doctor will review your allergies and your medical and surgical history. If there is any chance that you
may be pregnant or you are trying to get pregnant, tell your doctor before your surgery.
About oneweek before surgery, you will need to stop taking blood-thinning medications.
Beginning at midnight on the night before your surgery, you must not eat or drink
anything. This reduces the risk of vomiting during surgery.

You will need to have someone drive you home after surgery.

https://www.drugs.com/health-guide/cholecystectomy.html
How It's Done
No matter which type of surgery you have, you will be put under general anesthesia, making you unconscious during your
surgery. An intravenous (IV) line inserted into one of your veins will deliver fluids and medications.

Traditional surgery – The surgeon cuts a 6-inch incision in the upper right side of your abdomen and removes your
gallbladder. Often, a test called cholangiography is done during the operation to look for any stones that may have passed
into the main bile duct (in this test, a dye is injected into the bile ducts and X-rays are taken). If stones are seen on the X-
rays, they may be removed, and a tube may then be placed in the common bile duct (and coming out of the skin) for
drainage, until some time after the surgery. After the gallbladder is removed, the incision is closed with stitches. While in the
hospital, you gradually will resume eating a normal diet and get out of bed. Usually you stay in the hospital for two to five
days.

https://www.drugs.com/health-guide/cholecystectomy.html
 Laparoscopic surgery – The surgeon makes a small incision at the navel and puts air into the abdomen to make it
easier to see. This help to avoid damaging any organs with the incisions or instruments. Next the laparoscope is
inserted through the small incision at your navel. Once the laparoscope is inside your abdomen, a camera on the
laparoscope transmits images to a viewing screen. Three smaller incisions are made, and the surgical instruments are
inserted through these incisions. The surgeon cuts out the gallbladder, and removes the gallbladder through one of
the incisions, usually the one at your bellybutton. All of the instruments are removed, and the surgeon closes the
incisions with stitches or surgical tape. After you wake up from anesthesia, the IV line remains in place until you can
drink fluids on your own, usually within a few hours after surgery. If you are having a same-day procedure, you can
leave the hospital when you feel well enough to go home safely. You may be able to eat a light meal later that day (in
the evening). Sometimes patients stay in the hospital until the next morning.

https://www.drugs.com/health-guide/cholecystectomy.html
 laparoscopic surgery, the surgeon will switch to a
If there are any difficulties during a
traditional cholecystectomy. This may happen if there is too much bleeding, if there is much
scarring from previous surgery, if the gallbladder is difficult to remove, or if there is severe infection.

https://www.drugs.com/health-guide/cholecystectomy.html
 Cholecystitis
(Inflammation of the Gallbladder)

MAIN MENU
Cholecystitis is inflammation of the gallbladder that occurs most commonly because of an obstruction of
the cystic duct by gallstones arising from the gallbladder (cholelithiasis). Uncomplicated cholecystitis has an
excellent prognosis; the development of complications such as perforation or gangrene renders the prognosis less
favorable.

Signs and symptoms

The most common presenting symptom of acute cholecystitis is upper abdominal pain. The following
characteristics may be reported:
• Signs of peritoneal irritation may be present, and the pain may radiate to the right shoulder or scapula
• Pain frequently begins in the epigastric region and then localizes to the right upper quadrant (RUQ)
• Pain may initially be colicky but almost always becomes constant
• Nausea and vomiting are generally present, and fever may be noted
The physical examination may reveal the following:

• Fever, tachycardia, and tenderness in the RUQ or epigastric region, often with
guarding or rebound
• Palpable gallbladder or fullness of the RUQ (30-40% of patients)
• Jaundice (~15% of patients)

The absence of physical findings does not rule out the diagnosis of cholecystitis.

Patients with acalculous cholecystitis may present similarly to patients with calculous cholecystitis, but acalculous
cholecystitis frequently occurs suddenly in severely ill patients without a prior history of biliary colic. Often, patients
with acalculous cholecystitis may present with fever and sepsis alone, without history or physical examination findings
consistent with acute cholecystitis.
 Cholecystitis in elderly persons
Elderly patients (especially patients with diabetes) may present with vague symptoms and without many key historical
and physical findings. Pain and fever may be absent, and localized tenderness may be the only presenting sign. Elderly
patients may also progress to complicated cholecystitis rapidly and without warning.

Cholecystitis in children
The pediatric population may also present without many of the classic findings. Children who are at a higher risk for
developing cholecystitis include patients with sickle cell disease, seriously ill children, those on prolonged TPN, those with
hemolytic conditions, and those with congenital and biliary anomalies.[9]

McEvoy CF, Suchy FJ. Biliary tract disease in children. Pediatr Clin North Am. 1996 Feb. 43(1):75-98. [Medline].
Epidemiology

Age distribution for cholecystitis

The incidence of cholecystitis increases with age. The physiologic explanation for the increasing incidence of gallstone
disease in the elderly population is unclear. The increased incidence in elderly men has been linked to changing
androgen-to-estrogen ratios.
Sex distribution for cholecystitis
Gallstones are 2-3 times more frequent in females than in males, resulting in a higher incidence of calculous
cholecystitis in females. Elevated progesterone levels during pregnancy may cause biliary stasis, resulting in higher
rates of gallbladder disease in pregnant females. Acalculous cholecystitis is observed more often in elderly men.
Prevalence of cholecystitis by race and ethnicity
Cholelithiasis, the major risk factor for cholecystitis, has an increased prevalence in people of Scandinavian descent,
Pima Indians, and Hispanic populations, whereas cholelithiasis is less common among individuals from sub-Saharan
Africa and Asia.[6, 7] In the United States, white people have a higher prevalence than black people.
PATOPHYSIOLOGY
Ninety percent of cases of cholecystitis involve stones in the gallbladder (ie, calculous cholecystitis), with the other
10% of cases representing acalculous cholecystitis.

Acute calculous cholecystitis is caused by obstruction of the cystic duct, leading to distention of the gallbladder. As the
gallbladder becomes distended, blood flow and lymphatic drainage are compromised, leading to mucosal ischemia
and necrosis.

Although the exact mechanism of acalculous cholecystitis is unclear, several theories exist. Injury may be the result of
retained concentrated bile, an extremely noxious substance. In the presence of prolonged fasting, the gallbladder
never receives a cholecystokinin (CCK) stimulus to empty; thus, the concentrated bile remains stagnant in the lumen.

A study by Cullen et al demonstrated the ability of endotoxin to cause necrosis, hemorrhage, areas of fibrin deposition,
and extensive mucosal loss, consistent with an acute ischemic insult. Endotoxin also abolished the contractile response
to CCK, leading to gallbladder stasis.

Sitzmann JV, Pitt HA, Steinborn PA, et al. Cholecystokinin prevents parenteral nutrition induced biliary sludge in
humans. Surg Gynecol Obstet. 1990 Jan. 170(1):25-31.
 Etiology
Risk factors for calculous cholecystitis mirror those for cholelithiasis and include the following:
• Female sex
• Certain ethnic groups
• Obesity or rapid weight loss
• Drugs (especially hormonal therapy in women)
• Pregnancy
• Increasing age

Huffman JL, Schenker S. Acute acalculous cholecystitis - a review. Clin Gastroenterol Hepatol. 2009 Sep 9.
 Acalculous cholecystitis is related to conditions associated with biliary stasis, and include the following:
• Critical illness
• Major surgery or severe trauma/burns
• Sepsis
• Long-term total parenteral nutrition (TPN)
• Prolonged fasting

Other causes of acalculous cholecystitis include the following:

• Cardiac events, including myocardial infarction
• Sickle cell disease
• Salmonella infections
• Diabetes mellitus[5]
• Patients with AIDS who have cytomegalovirus, cryptosporidiosis, or microsporidiosis
Patients who are immunocompromised are at an increased risk of developing cholecystitis from a number of
different infectious sources. Idiopathic cases exist.

Huffman JL, Schenker S. Acute acalculous cholecystitis - a review. Clin Gastroenterol Hepatol. 2009 Sep 9.
Complications

Bacterial proliferation within the obstructed gallbladder results in empyema of the organ. Patients with empyema
may have a toxic reaction and may have more marked fever and leukocytosis. The presence of empyema
frequently requires conversion from laparoscopic to open cholecystectomy.
In rare instances, a large gallstone may erode through the gallbladder wall into an adjacent viscus, usually the
duodenum. Subsequently, the stone may become impacted in the terminal ileum or in the duodenal bulb and/or
pylorus, causing gallstone ileus.
Emphysematous cholecystitis occurs in approximately 1% of cases and is noted by the presence of gas in the
gallbladder wall from the invasion of gas-producing organisms, such as Escherichia coli, Clostridia perfringens, and
Klebsiella species. This complication is more common in patients with diabetes, has a male predominance, and is
acalculous in 28% of cases. Because of a high incidence of gangrene and perforation, emergency cholecystectomy is
recommended. Perforation occurs in up to 15% of patients.

Chiu HH, Chen CM, Mo LR. Emphysematous cholecystitis. Am J Surg. 2004 Sep. 188(3):325-6. [Medline].
Diagnosis
Laboratory tests are not always reliable, but the following findings may be diagnostically useful:
• Leukocytosis with a left shift may be observed
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels may be elevated in cholecystitis or
with common bile duct (CBD) obstruction
• Bilirubin and alkaline phosphatase assays may reveal evidence of CBD obstruction
• Amylase/lipase assays are used to assess for pancreatitis; amylase may also be mildly elevated in cholecystitis
• Alkaline phosphatase level may be elevated (25% of patients with cholecystitis)
• Urinalysis is used to rule out pyelonephritis and renal calculi
• All females of childbearing age should undergo pregnancy testing
Imaging recommendations
The 2010 American College of Radiology (ACR) Appropriateness Criteria offer the following imaging
recommendations[18] :
• Sonography is the preferred initial imaging test for the diagnosis of acute cholecystitis, and
scintigraphy is the preferred alternative.
• CT is a secondary imaging test that can identify extrabiliary disorders and complications of acute
cholecystitis, such as gangrene, gas formation, and perforation.
• CT with intravenous contrast is useful in diagnosing acute cholecystitis in patients with nonspecific
abdominal pain.
• MRI, often with intravenous gadolinium-based contrast medium, is also a possible secondary imaging
modality useful in confirming a diagnosis of acute cholecystitis.
• MRI without contrast is useful to eliminate radiation exposure in pregnant women for whom
sonograms have not indicated a clear diagnosis.
• Contrast agents should not be used in patients on dialysis unless absolutely necessary.
Histologic Findings
Edema and venous congestion are early acute changes. Acute cholecystitis is usually superimposed on a histologic
picture of chronic cholecystitis. Specific findings include fibrosis, flattening of the mucosa, and chronic inflammatory
cells. Mucosal herniations known as Rokitansky-Aschoff sinuses are related to increased hydrostatic pressure and
are present in 56% of cases. Focal necrosis and an influx of neutrophils may also be present. Advanced cases may
show gangrene or perforation.
Initial Therapy and Antibiotic Treatment

In acute cholecystitis, the initial treatment includes bowel rest, intravenous hydration, correction of electrolyte
abnormalities, analgesia, and intravenous antibiotics. For mild cases of acute cholecystitis, antibiotic therapy with a
single broad-spectrum antibiotic is adequate.
Some options include the following:
• The current Sanford guide recommendations include piperacillin/tazobactam (Zosyn, 3.375 g IV q6h or 4.5 g IV
q8h), ampicillin/sulbactam (Unasyn, 3 g IV q6h), or meropenem (Merrem, 1 g IV q8h). In severe life-
threatening cases, the Sanford Guide recommends imipenem/cilastatin (Primaxin, 500 mg IV q6h).
• Alternative regimens include a third-generation cephalosporin plus metronidazole (Flagyl, 1 g IV loading dose
followed by 500 mg IV q6h).
• Bacteria that are commonly associated with cholecystitis include Escherichia coli and Bacteroides fragilis, as well
as Klebsiella, Enterococcus, and Pseudomonas species.
• Emesis can be treated with antiemetics and nasogastric suction.
• Because of the rapid progression of acute acalculous cholecystitis to gangrene and perforation, early recognition and
intervention are required.
• Supportive medical care should include restoration of hemodynamic stability and antibiotic coverage for gram-
negative enteric flora and anaerobes if biliary tract infection is suspected.
• Daily stimulation of gallbladder contraction with intravenous cholecystokinin (CCK) has been shown by some to
effectively prevent the formation of gallbladder sludge in patients receiving total parenteral nutrition (TPN).
Conservative Treatment of Uncomplicated Cholecystitis
Outpatient treatment may be appropriate for cases of uncomplicated cholecystitis. If a patient can be treated as an
outpatient, discharge with antibiotics, appropriate analgesics, and definitive follow-up care. Criteria for outpatient
treatment include the following:
• Afebrile with stable vital signs
• No evidence of obstruction by laboratory values
• No evidence of common bile duct obstruction on ultrasonography
• No underlying medical problems, advanced age, pregnancy, or immunocompromised condition
• Adequate analgesia
• Reliable patient with transportation and easy access to a medical facility
• Prompt follow-up care
• The following medications may be appropriate in this setting:
• Prophylactic antibiotic coverage with levofloxacin (Levaquin, 500 mg PO qd) and metronidazole (500 mg PO bid), which
should provide coverage against the most common organisms
• Antiemetics, such as oral/rectal promethazine (Phenergan) or prochlorperazine (Compazine), to control nausea and to
prevent fluid and electrolyte disorders
• Analgesics, such as oral oxycodone/acetaminophen (Percocet) or hydrocodone/acetaminophen (Vicodin)
• Cholescystectomy
• Percutaneus Drainage
• Endoscopic Treatment
Prognosis
Uncomplicated cholecystitis has an excellent prognosis, with a very low mortality. Most patients with acute
cholecystitis have a complete remission within 1-4 days. However, 25-30% of patients either require surgery or
develop some complication.
Once complications such as perforation/gangrene develop, the prognosis becomes less favorable. Perforation occurs
in 10-15% of cases. Patients with acalculous cholecystitis have a mortality ranging from 10-50%, which far exceeds the
expected 4% mortality observed in patients with calculous cholecystitis. In patients who are critically ill with
acalculous cholecystitis and perforation or gangrene, mortality can be as high as 50-60%.
The severity of acute cholecystitis also has an impact on the risk of iatrogenic bile duct injury during
cholecystectomy.[8] Tornqvist et al reported a doubling of the risk for sustaining a biliary lesion in patients with
ongoing acute cholecystitis compared to those without acute cholecystitis. Patients with Tokyo grade II (moderate)
acute cholecystitis and those with Tokyo grade III (severe) cholecystitis had, respectively, over double and more than
eight times the risk of bile duct injury compared to those without acute cholecystitis. The risk of biliary injury was
reduced by 52% with intention to use intraoperative cholangiography.
CHOLANGITIS

MAIN MENU
 Cholangitis is an infection of the biliary tract with the potential to cause significant morbidity and mortality.
Many patients with acute cholangitis respond to antibiotic therapy; however, patients with severe or toxic cholangitis
may not respond and may require emergency biliary drainage. Jean M. Charcot recognized this illness in 1877 when he
described a triad of fever, jaundice, and right upper quadrant pain. In 1959, Reynolds and Dargon described a more
severe form of the illness that included the additional components of septic shock and mental confusion, which is
referred to as the Reynolds pentad.

Lee JG. Diagnosis and management of acute cholangitis. Nat Rev Gastroenterol Hepatol. 2009 Aug 4.
 Pathophysiology
Historically, choledocholithiasis was the most common cause of biliary tract obstruction resulting in cholangitis. Over
the past 20 years, biliary tract manipulations/interventions and stents have reportedly become more common causes
of cholangitis. Hepatobiliary malignancies are a less common cause of biliary tract obstruction and subsequent bile
contamination.

Lee JG. Diagnosis and management of acute cholangitis. Nat Rev Gastroenterol Hepatol. 2009 Aug 4.
Epidemiology

Mortality/Morbidity
The condition has significant potential for mortality and morbidity, especially if left untreated. Reported mortality rates
vary from 13 to 88%.
Race
Cholangitis is reported in all races. One variant, Asian cholangitis (also referred to as recurrent pyogenic cholangitis), is
observed with increased frequency in Southeast Asia.[2]
Sex
The condition is reported in both females and males and has no clear predominance in either.
Age
The condition mostly occurs in adults, with a reported median age at onset of 50-60 years.
 History
A history of choledocholithiasis or recent biliary tract manipulation associated with fever, abdominal (right upper
quadrant) pain, and jaundice (the Charcot triad) is highly suggestive of cholangitis. Fever reportedly occurs in nearly 95%
of patients with cholangitis. Approximately 90% of patients have right upper quadrant tenderness, and 80% have
jaundice.
According to Fujii et al, the 2007 Tokyo guidelines for the diagnosis and treatment of acute cholangitis were mostly
acceptable.[3] However, classification into mild or moderate grade using the guidelines could be challenging, so it was
necessary for clinicians to carefully distinguish organ dysfunction associated with cholangitis itself from dysfunction
associated with the underlying disease in determining the severity of the disease.
Similarly, Nishino et al found that the 2013 Tokyo guidelines for the diagnosis and treatment of acute cholangitis are
practical, but they may underestimate some cases that necessitate urgent/early biliary drainage as mild disease.[4] The
investigators developed a scoring system that took into consideration the following five predictors, which they indicate
may improve identification of patients at high risk of needing urgent/early biliary drainage[4] :
• Blood urea nitrogen level above 20 mg/dL
• Platelet count below 120,000/μ L
• Serum albumin level below 3.0 g/dL
• The presence of systemic inflammatory response syndrome (SIRS)
• Age of 75 years or older

Fujii Y, Ohuchida J, Chijiiwa K, Yano K, Imamura N, Nagano M, et al. Verification of Tokyo Guidelines for diagnosis and management of acute cholangitis. J
Hepatobiliary Pancreat Sci. 2011 Oct 28.
Physical examination
may reveal fever, icterus, jaundice, and abdominal

pain.
 Causes

The two main causes of cholangitis are biliary tract manipulation and common bile duct stones. Other possible
causes of biliary tract obstruction that may lead to infection include strictures, tumors, choledochal/biliary cysts,
or sump syndrome. Hepatolithiasis is also a possible cause of cholangitis and is observed more frequently in East
Asia. More than 90% of patients with hepatolithiasis have calcium bilirubinate stones, also referred to as brown
pigment stones.

Li FY, Cheng NS, Mao H, Jiang LS, et al. Significance of controlling chronic proliferative cholangitis in the treatment of hepatolithiasis. World J Surg. 2009 Jul 30.
epub ahead of print
Laboratory Studies
See the list below:
• Obtain CBC count, liver function tests, and blood cultures.
• Common laboratory findings include leukocytosis, hyperbilirubinemia (patients with a malignant obstruction
generally have a significantly higher bilirubin level than those with a benign obstruction), and elevated alkaline
phosphatase levels.
• Other possible laboratory findings include elevation of transaminases and serum amylase levels (due to possible
concurrent pancreatitis from stone impaction at the ampulla of Vater).
• Blood culture findings are positive in nearly 50% of patients.
• Bile culture findings are positive in nearly all patients.
• Multiple organisms are identified in approximately 60% of patients. Commonly reported aerobic organisms
include Escherichia coli and Klebsiella and Enterococcus species. The most commonly reported anaerobic organism
is Bacteroides fragilis.
Treatment

Administration of broad-spectrum intravenous antibiotics and correction of fluid and electrolyte imbalances
constitute essential medical care for cholangitis.
• High biliary pressures caused by an obstruction may impair the biliary secretion of antibiotics; therefore,
treatment may require decompression and drainage of the biliary system.
• For patients with severe cholangitis, endoscopic drainage has replaced emergency surgical common duct
exploration and T-tube drainage as standard treatment.
• Percutaneous transhepatic biliary drainage (PTBD) is another possible nonsurgical method of biliary
drainage.
Surgical Care
Endoscopic biliary drainage and decompression have usually replaced surgery as the initial treatment of severe
cholangitis. Surgical decompression is appropriate for patients in whom endoscopic or transhepatic drainage is
unsuccessful or unavailable.
Following adequate biliary drainage and decompression for acute cholangitis with bacteremia, Park et al found no
significant differences in the recurrence of acute cholangitis and 30-day mortality between early switch to oral
antibiotic therapy and standard 10-day intravenous antibiotic therapy

Park TY, Choi JS, Song TJ, Do JH, Choi SH, Oh HC. Early oral antibiotic switch compared with conventional intravenous antibiotic therapy for acute
cholangitis with bacteremia. Dig Dis Sci. 2014 Nov. 59(11):2790-6.
PANCREATITIS

MAIN MENU
Practice Essentials

Recognizing patients with severe acute pancreatitis as soon as possible is critical for achieving optimal outcomes.
Management depends largely on severity. Medical treatment of mild acute pancreatitis is relatively straightforward.
Treatment of severe acute pancreatitis involves intensive care. Surgical intervention (open or minimally invasive) is
indicated in selected cases.

Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, et al. Classification of acute pancreatitis--2012: revision of the Atlanta classification and
definitions by international consensus. Gut. 2013 Jan. 62(1):102-11
http://charlestongi.com/wp-content/uploads/2015/05/chronicpancreatitis.jpg
Pathogenesis of acute pancreatitis
Acute pancreatitis may occur when factors involved in maintaining cellular homeostasis are out of balance. The
initiating event may be anything that injures the acinar cell and impairs the secretion of zymogen granules; examples
include alcohol use, gallstones, and certain drugs.
At present, it is unclear exactly what pathophysiologic event triggers the onset of acute pancreatitis. It is believed,
however, that both extracellular factors (eg, neural and vascular response) and intracellular factors (eg, intracellular
digestive enzyme activation, increased calcium signaling, and heat shock protein activation) play a role. In addition,
acute pancreatitis can develop when ductal cell injury leads to delayed or absent enzymatic secretion, as seen in
patients with the CFTR gene mutation.
Once a cellular injury pattern has been initiated, cellular membrane trafficking becomes chaotic, with the following
deleterious effects:
• Lysosomal and zymogen granule compartments fuse, enabling activation of trypsinogen to trypsin
• Intracellular trypsin triggers the entire zymogen activation cascade
• Secretory vesicles are extruded across the basolateral membrane into the interstitium, where molecular fragments
act as chemoattractants for inflammatory cells

GET SMASHED
Activated neutrophils then exacerbate the problem by releasing superoxide (the respiratory burst) or proteolytic
enzymes (cathepsins B, D, and G; collagenase; and elastase). Finally, macrophages release cytokines that further
mediate local (and, in severe cases, systemic) inflammatory responses. The early mediators defined to date are tumor
necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-8.
These mediators of inflammation cause an increased pancreatic vascular permeability, leading to hemorrhage,
edema, and eventually pancreatic necrosis. As the mediators are excreted into the circulation, systemic
complications can arise, such as bacteremia due to gut flora translocation, acute respiratory distress syndrome (ARDS),
pleural effusions, gastrointestinal (GI) hemorrhage, and renal failure.
The systemic inflammatory response syndrome (SIRS) can also develop, leading to the development of systemic
shock. Eventually, the mediators of inflammation can become so overwhelming that hemodynamic instability and
death ensue.
In acute pancreatitis, parenchymal edema and peripancreatic fat necrosis occur first; this is known as acute
edematous pancreatitis. When necrosis involves the parenchyma, accompanied by hemorrhage and dysfunction of
the gland, the inflammation evolves into hemorrhagic or necrotizing pancreatitis. Pseudocysts and pancreatic
abscesses can result from necrotizing pancreatitis because enzymes can be walled off by granulation tissue
(pseudocyst formation) or via bacterial seeding of pancreatic or peripancreatic tissue (pancreatic abscess
formation).
Li et al compared 2 set of patients with severe acute pancreatitis—one with acute renal failure and the other
without it—and determined that a history of renal disease, hypoxemia, and abdominal compartment syndrome
were significant risk factors for acute renal failure in patients with severe acute pancreatitis.[5] In addition, patients
with acute renal failure were found to have a significantly greater average length of stay in the hospital and in the
intensive care unit (ICU), as well as higher rates of pancreatic infection and mortality.
http://intranet.tdmu.edu.ua/
http://epomedicine.com/wp-content/uploads/2015/10/acute-pancreatitis-pathophysiology.jpg
Signs and symptoms
Symptoms of acute pancreatitis include the following:
• Abdominal pain (cardinal symptom): Characteristically dull, boring,
and steady; usually sudden in onset and gradually becoming more
severe until reaching a constant ache; most often located in the
upper abdomen and may radiate directly through to the back
• Nausea and vomiting, sometimes with anorexia
• Diarrhea
Patients may have a history of the following:
• Recent operative or other invasive procedures
• Family history of hypertriglyceridemia
• Previous biliary colic and binge alcohol consumption (major causes of acute pancreatitis)
The following physical findings may be noted, varying with the severity of the disease:
• Fever (76%) and tachycardia (65%); hypotension
• Abdominal tenderness, muscular guarding (68%), and distention (65%); diminished or absent bowel sounds
• Jaundice (28%)
• Dyspnea (10%); tachypnea; basilar rales, especially in the left lung
• In severe cases, hemodynamic instability (10%) and hematemesis or melena (5%); pale, diaphoretic, and
listless appearance
• Occasionally, extremity muscular spasms secondary to hypocalcemia
The following uncommon physical findings are associated with severe necrotizing pancreatitis:
• Cullen sign (bluish discoloration around the umbilicus resulting from hemoperitoneum)
• Grey-Turner sign (reddish-brown discoloration along the flanks resulting from retroperitoneal blood
dissecting along tissue planes); more commonly, patients may have a ruddy erythema in the flanks secondary to
extravasated pancreatic exudate
• Erythematous skin nodules, usually no larger than 1 cm and typically located on extensor skin surfaces; polyarthritis
Diagnosis
Once a working diagnosis of acute pancreatitis is reached, laboratory tests are obtained to support the clinical
impression, such as the following:
• Serum amylase and lipase
• Liver-associated enzymes
• Blood urea nitrogen (BUN), creatinine, and electrolytes
• Blood glucose
• Serum cholesterol and triglyceride
• Complete blood count (CBC) and hematocrit; NLR
• C-reactive protein (CRP)
• Arterial blood gas values
• Serum lactic dehydrogenase (LDH) and bicarbonate
• Immunoglobulin G4 (IgG4)
Management
Medical management of mild acute pancreatitis is relatively straightforward; however, patients with severe acute
pancreatitis require intensive care.
Initial supportive care includes the following:
• Fluid resuscitation
• Nutritional support
• Antibiotic therapy is employed as follows: Antibiotics (usually of the imipenem class) should be used in
any case of pancreatitis complicated by infected pancreatic necrosis but should not be given routinely for fever,
especially early in the presentation
• Antibiotic prophylaxis in severe pancreatitis is controversial; routine use of antibiotics as prophylaxis against
infection in severe acute pancreatitis is not currently recommended
Surgical intervention, whether by minimally
invasive or conventional open techniques, is
indicated when an anatomic complication
amenable to a mechanical solution is present (eg,
acute necrotizing pancreatitis in which the necrotic
phlegmon is excised to limit a potential site of
sepsis, or hemorrhagic pancreatitis in which
surgical control of bleeding is warranted).
Depending on the situation and local expertise, this
may require the talents of an interventional
radiologist, an interventional endoscopist, or
surgeon (individually or in combination).
The images below provide examples of the
treatment of severe acute pancreatitis by means of Endoscopic retrograde cholangiopancreatography excluded suppurative cholangitis and established the
presence of anular pancreas divisum. Dorsal pancreatogram showed extravasation into retroperitoneum,
minimally invasive techniques. and sphincterotomy was performed on minor papilla. Pigtail nasopancreatic tube was then inserted into
dorsal duct and out into retroperitoneal fluid collection. The other end of the tube was attached to bulb
suction and monitored every shift.
 Gallstone pancreatitis
It is optimal for patients admitted with gallstone pancreatitis to undergo cholecystectomy before discharge, rather than
being scheduled for a later date as an outpatient. Patients discharged with gallstone pancreatitis without a
cholecystectomy are at high risk for recurrent bouts of pancreatitis.
Aboulian et al found that in patients with mild gallstone pancreatitis, performing laparoscopic cholecystectomy within 48
hours of admission—regardless of whether abdominal pain or laboratory abnormalities had resolved—resulted in a
shorter hospital stay and had no apparent impact on the technical difficulty of the procedure or the perioperative
complication rate. If the imaging and laboratory study findings are consistent with severe acute gallstone pancreatitis
that is not responding to supportive therapy or with ascending cholangitis with worsening signs and symptoms of
obstruction, early endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy and stone extraction is
indicated.

Aboulian A, Chan T, Yaghoubian A, Kaji AH, Putnam B, Neville A, et al. Early cholecystectomy safely decreases hospital stay in patients
with mild gallstone pancreatitis: a randomized prospective study. Ann Surg. 2010 Apr. 251(4):615-9
CA PANCREAS

MAIN MENU
Pancreatic cancer is the fourth leading cause of cancer deaths, being responsible for
7% of all cancer-related deaths in both men and women. Approximately 75% of all pancreatic carcinomas occur
within the head or neck of the pancreas, 15-20% occur in the body of the pancreas, and 5-10% occur in the tail.
See the image below.

National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Pancreatic Adenocarcinoma, v.2.2015. Available
at http://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf. Accessed: October 20, 2015.
Epidemiology
Incidence in the United States
The American Cancer Society estimates that in the United States in 2015, about 48,960 new cases of pancreatic cancer
(24,840 in men and 24,120 in women) will be diagnosed.[7] The overall incidence rate of pancreatic cancer was stable
from 2007 to 2011, after increasing slowly over the previous decade. The incidence rate in men has been stable since
1993. In women, however, the incidence has been increasing by 0.6% per year since 1994.[8] . These trends probably
represent the effect of changing smoking rates for men and women.
International incidence
Worldwide, pancreatic cancer ranks 13th in incidence but 8th as a cause of cancer death.[36]
Most other countries have incidence rates of 8-12 cases per 100,000 persons per year. In some areas of the world,
pancreatic cancer is quite infrequent; for example, the incidence in India is less than 2 cases per 100,000 persons per
year.

Anderson KE, Mack T, Silverman D. Cancer of the pancreas. Schottenfeld D, Fraumeni JF Jr. Cancer Epidemiology and
Prevention. 3rd Ed. New York: Oxford University Press; 2006.
Types of pancreatic cancer
Of all pancreatic cancers, 80% are adenocarcinomas of the ductal epithelium. Only 2% of tumors of the exocrine
pancreas are benign.

Less common histologic appearances of exocrine pancreatic cancers include giant cell carcinoma, adenosquamous
carcinoma, microglandular adenocarcinoma, mucinous carcinoma, cystadenocarcinoma, papillary cystic carcinoma,
acinar cystadenocarcinoma, and acinar cell cystadenocarcinoma. Very rarely, primary connective tissue cancers of the
pancreas can occur. The most common of these is primary pancreatic lymphoma
Pancreatic cancer. Gross section of an adenocarcinoma of the pancreas measuring 5 X 6 cm resected
from the pancreatic body and tail. Although the tumor was considered to have been fully resected and
had not spread to any nodes, the patient died of recurrent cancer within 1 year.
Typically, pancreatic cancer first metastasizes to regional lymph nodes, then to the liver and, less
commonly, to the lungs. It can also directly invade surrounding visceral organs such as the duodenum,
stomach, and colon, or it can metastasize to any surface in the abdominal cavity via peritoneal spread.
Ascites may result, and this has an ominous prognosis. Pancreatic cancer may spread to the skin as
painful nodular metastases. Metastasis to bone is uncommon.
Pancreatic cancer rarely spreads to the brain, but it can produce meningeal carcinomatosis.
Etiology
Pancreatic cancers can arise from the exocrine and endocrine portions of the pancreas, but 95% of
them develop from the exocrine portion, including the ductal epithelium, acinar cells,
connective tissue, and lymphatic tissue. Approximately 75% of all pancreatic carcinomas occur
within the head or neck of the pancreas, 15-20% occur in the body of the pancreas, and 5-10%
occur in the tail.
Estimates indicate that 40%
of pancreatic cancer cases are sporadic in nature. Another
30% are related to smoking, and 20% may be associated with dietary factors.
Only 5-10% are hereditary in nature.[9]
Diabetes mellitus may be associated with a 2-fold increase in the risk of developing pancreatic cancer. Less
than 5% of all pancreatic cancers are related to underlying chronic pancreatitis.
Alcohol consumption does not appear to be an independent risk factor for pancreatic cancer unless it is
associated with chronic pancreatitis.

Raimondi S, Maisonneuve P, Lowenfels AB. Epidemiology of pancreatic cancer: an overview. Nat Rev Gastroenterol Hepatol. 2009 Dec.
6(12):699-708
Signs and symptoms
The initial symptoms of pancreatic cancer are often quite nonspecific and subtle in onset. Patients typically report the
gradual onset of nonspecific symptoms such as anorexia, malaise, nausea, fatigue, and midepigastric
or back pain.
Patients with pancreatic cancer may present with the following signs and symptoms:
• Significant weight loss: Characteristic feature of pancreatic cancer
• Midepigastric pain: Common symptom of pancreatic cancer, sometimes with radiation of the pain to the
midback or lower-back region
• Often, unrelenting pain: Nighttime pain often a predominant complaint
• Onset of diabetes mellitus within the previous year
• Painless obstructive jaundice: Most characteristic sign of cancer of head of the pancreas
• Pruritus: Often the patient's most distressing symptom
• Depression
• Migratory thrombophlebitis (ie, Trousseau sign) and venous thrombosis: May be the first
presentation
• Palpable gallbladder (ie, Courvoisier sign)
• Developing, advanced intra-abdominal disease: Presence of ascites, a palpable abdominal mass,
hepatomegaly from liver metastases, or splenomegaly from portal vein obstruction
• Advanced disease: Paraumbilical subcutaneous metastases (or Sister Mary Joseph nodule or
nodules)
• Possible presence of palpable metastatic mass in the rectal pouch (Blumer's shelf)
• Possible presence of palpable metastatic cervical nodes: Nodes may be palpable behind the medial
end of the left clavicle (Virchow's node) and other areas in the cervical region
Physical Examination
Pain is the most common presenting symptom in patients with pancreatic cancer. As previously mentioned, the pain
typically takes the form of mild to moderate midepigastric tenderness. In some cases, radiation of the pain to the
midback or lower-back region occurs. Such radiation is worrisome, as it indicates retroperitoneal invasion of the
splanchnic nerve plexus by the tumor.
However, at the time of initial presentation, about one third of patients may not have pain, one third have moderate
pain, and one third have severe pain. All patients experience pain at some point in their clinical course.
Patients with clinical jaundice may also have a palpable gallbladder (ie, Courvoisier sign) and may have skin
excoriations from unrelenting pruritus.
Patients presenting with or developing advanced intra-abdominal disease may have ascites, a palpable abdominal mass,
hepatomegaly from liver metastases, or splenomegaly from portal vein obstruction.
Subcutaneous metastases (referred to as a Sister Mary Joseph nodule or nodules) in the paraumbilical area signify
advanced disease.
A metastatic mass in the rectal pouch may be palpable on rectal examination (Blumer's shelf).
A metastatic node may be palpable behind the medial end of the left clavicle (Virchow's node). However, other nodes in
the cervical area may also be involved. Indeed, prior to the advent of computed tomography (CT) scanners to assess
intra-abdominal disease, pancreatic cancer accounted for some 25% of adenocarcinomas of the cervical nodes, primary
site unknown.
Diagnosis
Pancreatic cancer is notoriously difficult to diagnose in its early stages.

Testing
The laboratory findings in patients with pancreatic cancer are usually nonspecific. Patients with advanced pancreatic
cancers and weight loss may have general laboratory evidence of malnutrition (eg, low serum albumin or cholesterol
level).
Potentially useful tests in patients with suspected pancreatic cancer include the following:
• CBC count
• Hepatobiliary tests: Patients with obstructive jaundice show significant elevations in bilirubin (conjugated and total),
ALP, GGT, and, to a lesser extent, AST and ALT
• Serum amylase and/or lipase levels: Elevated in less than 50% of patients with resectable pancreatic cancers and in
only 25% of patients with unresectable tumors
• Tumor markers such as CA
19-9 antigen and CEA: 75-85% have elevated CA 19-9 levels; 40-
45% have elevated CEA levels
Imaging studies
Imaging studies that aid in the diagnosis of pancreatic cancer include the following:
• CT scanning
• Transcutaneous ultrasonography
• Endoscopic ultrasonography
• Magnetic resonance imaging
• Endoscopic retrograde cholangiopancreatography
• Positron emission tomography scanning
Management
Surgery is the primary mode of treatment for pancreatic cancer. However, an important role exists for chemotherapy
and/or radiation therapy.

Surgical options
Curative resection options include the following:
• Pancreaticoduodenectomy (Whipple Procedure), with/without sparing of the pylorus
• Total pancreatectomy
• Distal pancreatectomy
Chemotherapy
Antineoplastic agents and combinations of agents used in managing pancreatic carcinoma include the
following:
• Gemcitabine monotherapy: For symptomatic patients with metastatic or locally advanced
unresectable disease with poor performance status [1]
• GTX regimen (gemcitabine, docetaxel and capecitabine) [1]
• Gemcitabine and albumin-bound paclitaxel [1]
• FOLFIRINOX (LV5-FU [leucovorin/5-fluorouracil] plus oxaliplatin plus irinotecan): National
Comprehensive Cancer Network recommends as first-line treatment for patients with metastatic or locally
advanced unresectable disease with good performance status
• Paclitaxel protein bound 125 mg/m 2 plus gemcitabine 1000 mg/m 2 IV over 30-40 min on Days 1, 8, and 15
of each 28-day cycle
• 5-FU
• Erlotinib plus gemcitabine
• Capecitabine monotherapy or capecitabine plus erlotinib: May provide second-line therapy benefit in
patient's refractory to gemcitabine

Adjuvant therapy with gemcitabine is accepted as standard therapy for surgically resected pancreatic cancer.

[Guideline] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Pancreatic Adenocarcinoma, v.2.2015.
Available at http://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf. Accessed: October 20, 2015.
FATTY LIVER

MAIN MENU
Fatty liver, or steatosis, is a term that describes the buildup of fat in the liver. While it’s normal to
have some fat in your liver, more than 5 to 10 percent of your liver weight is fat in the case of fatty liver. Fatty liver is a
reversible condition that can be resolved with changed behaviors.

Fatty liver is common. Around 10 to 20 percent of Americans have too much fat in their liver, but no inflammation or
damage is present. Most cases of fatty liver are detected in people between ages 40 and 60. When fatty liver is caused
by an underlying condition, it can become harmful to the liver if the cause is not recognized and treated
What Are the Symptoms of Fatty Liver?
Fatty liver typically has no associated symptoms. You may experience fatigue or vague abdominal
discomfort. Your liver may become slightly enlarged, and your doctor can detect this during a physical
exam.
Excess fat can cause liver inflammation. If your liver becomes inflamed, you may have a poor
appetite, weight loss, abdominal pain, weakness, and confusion.
What Are the Causes of Fatty Liver?

The most common cause of fatty liver is alcoholism and heavy drinking. In many cases, doctors don’t know
what causes fatty liver in people who are not alcoholics.

Fatty liver develops when the body creates too much fat or cannot metabolize fat fast enough. The excess fat
is stored in liver cells where it accumulates to form fatty liver disease. Eating a high-fat diet may not directly
result in fatty liver.
Besides alcoholism, other common causes of fatty liver include:
• obesity
• hyperlipidemia, or high levels of fats in the blood
• diabetes
• genetic inheritance
• rapid weight loss
• side effect of certain medications, including aspirin, steroids, tamoxifen, and tetracycline
There are four types of fatty liver:

Nonalcoholic Fatty Liver

Nonalcoholic fatty liver (NAFL) develops when the liver has difficulty breaking down fats, which causes a buildup in the
liver tissue. The cause is not related to alcohol. NAFL is diagnosed when more than 10 percent of the liver is fat.

Alcoholic Fatty Liver

Alcoholic fatty liver is the earliest stage of alcohol-related liver disease. Heavy drinking damages the liver, and the liver
cannot break down fats as a result. Abstaining from alcohol will likely cause the fatty liver to subside. Within six weeks
of not drinking alcohol, the fat will disappear. However, if excessive alcohol use continues, cirrhosis may develop.
Nonalcoholic Steatohepatitis (NASH)
When the fat builds up enough, it will cause the liver to swell. If the original cause is not from alcohol, it’s called
nonalcoholic steatohepatitis (NASH). This disease can impair liver function.
Symptoms can be seen with this disease. These include:
• appetite loss
• nausea
• vomiting
• abdominal pain
• yellowing of the skin (jaundice)
If left untreated, NASH can progress to permanent scarring of the liver and eventual liver failure.

Acute Fatty Liver of Pregnancy

Acute fatty liver is a rare complication of pregnancy that can be life-threatening.
Symptoms begin in the third trimester. These include:
• persistent nausea and vomiting
• pain in the upper-right abdomen
• jaundice
• general malaise
Women who are pregnant will be screened for this condition. Most women improve after delivery and have no lasting
effects.
RISK FACTORS:
Fatty liver is the buildup of extra fats in the liver, it’s more likely to develop if you’re overweight or obese. Having type
2 diabetes also may increase your risk for fatty liver. Fat accumulation in the liver has been linked to insulin
resistance, which is the most common cause of type 2 diabetes.
Other factors that may increase your risk for fatty liver are:
• excessive alcohol use
• taking more than the recommended doses of certain over-the-counter medications, such as acetaminophen
• pregnancy
• high cholesterol
• high triglyceride levels
• malnutrition
• metabolic syndrome
How Is Fatty Liver Treated?
There isn’t a medication or surgery to treat fatty liver. Instead, your doctor will offer recommendations to
reduce your risk factors. These recommendations include:
• limiting or avoiding alcoholic beverages
• managing your cholesterol
• losing weight
• controlling your blood sugar
If you have fatty liver because of obesity or unhealthy eating habits, your doctor may also suggest that you
increase physical activity and eliminate certain types of food from your diet. Reducing the number of
calories you eat each day can help you lose weight and heal your liver.
You can also reverse fatty liver disease by reducing or eliminating fatty foods and foods high in sugar from
your diet. Choose healthier foods like fresh fruits, vegetables, and whole grains. Replace red meats with
lean animal proteins like chicken and fish.