Cholecystolithiasis

cholecystolithiasis
The presence of one or more gallstones in the gallbladder

A gallstone is a crystalline concretion formed within the gallbladder by accretion of bile components. These calculi are formed in the gallbladder, but may pass distally into other parts of the biliary tract such as the cystic duct, common bile duct, pancreatic duct, or the ampulla of Vater. Presence of gallstones in the gallbladder may lead to acute cholecystitis, an inflammatory condition characterized by retention of bile in the gallbladder and often secondary infection by intestinal microorganisms, predominantly Escherichia coli and Bacteroides species. Presence of gallstones in other parts of the biliary tract can cause obstruction of the bile ducts, which can lead to serious conditions such as ascending cholangitis or pancreatitis. Either of these two conditions can be life-threatening, and are therefore considered to be medical emergencies. Presence of stones in the gallbladder is referred to as cholelithiasis (from the Greek: chol-, "bile" + lith-, "stone" + iasis-, "process"). If gallstones migrate into the ducts of the biliary tract, the condition is referred to as choledocholithiasis (from the Greek: chol-, "bile" + docho-, "duct" + lith-, "stone" + iasis-, "process"). Choledocholithiasis is frequently associated with obstruction of the biliary tree, which in turn can lead to acute ascending cholangitis (from the Greek: chol-, "bile + ang-, "vessel" + itis-, "inflammation"), a serious infection of the bile ducts. Gallstones within the ampulla of Vater can obstruct the exocrine system of the pancreas, which in turn can result in pancreatitis.

Characteristics and composition

Gallstones can vary in size from as small as a grain of sand to as large as a golf ball. The gallbladder may contain a single large stone or many smaller ones. Pseudoliths, sometime referred to as sludge, are thick secretions that may be present within the gallbladder, either alone or in conjunction with fully formed gallstones. The clinical presentation is similar to that of cholelithiasis. The composition of gallstones is affected by age, diet and ethnicity. On the basis of their composition, gallstones can be divided into the following types:

Cholesterol stones Cholesterol stones vary in color from light-yellow to dark-green or brown and are oval 2 to 3
cm in length, often having a tiny dark central spot. To be classified as such, they must be at least 80% cholesterol by weight (or 70%, according to the Japanese classification system).

Pigment stones

Pigment stones are small, dark stones made of bilirubin and calcium salts that are found in bile. They contain less than 20% of cholesterol (or 30%, according to the Japanese classification system).

Mixed stones
Mixed gallstones typically contain 2080% cholesterol (or 3070%, according to the Japanese classification system). Other common constituents are calcium carbonate, palmitate phosphate, bilirubin, and other bile pigments. Because of their calcium content, they are often radiographically visible.

Cholelithiasis
Signs and symptoms
Gallstones may be asymptomatic, even for years. These gallstones are called "silent stones" and do not require treatment. Symptoms commonly begin to appear once the stones reach a certain size (>8 mm). A characteristic symptom of gallstones is a "gallstone attack", in which a person may experience intense pain in the upper-right side of the abdomen, often accompanied by nausea and vomiting, that steadily increases for approximately 30 minutes to several hours. A patient may also experience referred pain between the shoulder blades or below the right shoulder. These symptoms may resemble those of a "kidney stone attack". Often, attacks occur after a particularly fatty meal and almost always happen at night. Other symptoms include abdominal bloating, intolerance of fatty foods, belching, gas, and indigestion. A positive Murphy's sign is a common finding on physical examination.

Causes
Gallstone risk factors include overweight, age near or above 40, female, or pre-menopausal; the condition is more prevalent in caucasians than in people of other races. A lack of melatonin could significantly contribute to gallbladder stones, as melatonin both inhibits cholesterol secretion from the gallbladder, enhances the conversion of cholesterol to bile, and is an antioxidant, capable of reducing oxidative stress to the gallbladder. Researchers believe that gallstones may be caused by a combination of factors, including inherited body chemistry, body weight, gallbladder motility (movement), and perhaps diet. The absence of such risk factors does not, however, preclude the formation of gallstones. No clear relationship has been proven between diet and gallstone formation; however, lowfiber, high-cholesterol diets and diets high in starchy foods have been suggested as contributing to gallstone formation. Other nutritional factors that may increase risk of gallstones include rapid weight loss, constipation, eating fewer meals per day, eating less fish, and low intakes of the nutrients folate, magnesium, calcium, and vitamin C. On the other hand, wine and whole-

grain bread may decrease the risk of gallstones. Pigment gallstones are most commonly seen in the developing world. Risk factors for pigment stones include hemolytic anemias (such as sicklecell disease and hereditary spherocytosis), cirrhosis, and biliary tract infections. People with erythropoietic protoporphyria (EPP) are at increased risk to develop gallstones. Additionally, prolonged use of proton pump inhibitors has been shown to decrease gallbladder function, potentially leading to gallstone formation.

Pathophysiology
Cholesterol gallstones develop when bile contains too much cholesterol and not enough bile salts. Besides a high concentration of cholesterol, two other factors are important in causing gallstones. The first is how often and how well the gallbladder contracts; incomplete and infrequent emptying of the gallbladder may cause the bile to become overconcentrated and contribute to gallstone formation. The second factor is the presence of proteins in the liver and bile that either promote or inhibit cholesterol crystallization into gallstones. In addition, increased levels of the hormone estrogen as a result of pregnancy, hormone therapy, or the use of combined (estrogen-containing) forms of hormonal contraception, may increase cholesterol levels in bile and also decrease gallbladder movement, resulting in gallstone formation.

Diagnosis: Treatment
Medical
Cholesterol gallstones can sometimes be dissolved by oral ursodeoxycholic acid, but it may be necessary for the patient to take this medication for up to two years. Gallstones may recur, however, once the drug is stopped. Obstruction of the common bile duct with gallstones can sometimes be relieved by endoscopic retrograde sphincterotomy (ERS) following endoscopic retrograde cholangiopancreatography (ERCP). Gallstones can be broken up using a procedure called extracorporeal shock wave lithotripsy (often simply called "lithotripsy"), which is a method of concentrating ultrasonic shock waves onto the stones to break them into tiny pieces. They are then passed safely in the feces. However, this form of treatment is suitable only when there is a small number of gallstones.

Cholecystectomy (gallbladder removal) has a 99% chance of eliminating the recurrence of cholelithiasis. Only symptomatic patients must be indicated to surgery. The lack of a gallbladder may have no negative consequences in many people. However, there is a portion of the population between 10 and 15% who develop a condition called postcholecystectomy syndrome which may cause gastrointestinal distress and persistent pain in the upper-right abdomen, as well as a 10% chance of developing chronic diarrhea.

There are two surgical options for cholecystectomy:

Open cholecystectomy: This procedure is performed via an incision into the abdomen (laparotomy) below the right lower ribs. Recovery typically consists of 35 days of hospitalization, with a return to normal diet a week after release and normal activity several weeks after release.[4] Laparoscopic cholecystectomy: This procedure, introduced in the 1980s, is performed via three to four small puncture holes for a camera and instruments. Post-operative care typically includes a same-day release or a one night hospital stay, followed by a few days of home rest and pain medication.[4] Laparoscopic cholecystectomy patients can, in general, resume normal diet and light activity a week after release, with some decreased energy level and minor residual pain continuing for a month or two. Studies have shown that this procedure is as effective as the more invasive open cholecystectomy, provided the stones are accurately located by cholangiogram prior to the procedure so that they can all be removed.

Choledocholithiasis
Choledocholithiasis is the presence of gallstones in the common bile duct. This condition causes jaundice and liver cell damage, and requires treatment by cholecystectomy and/or ERCP.

Signs and symptoms

A positive Murphy's sign is a common finding on physical examination. 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.

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. The diagnosis is confirmed with either an Magnetic resonance cholangiopancreatography (MRCP), 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 removing the stone using ERCP. Typically, the gallbladder is then removed, an operation called cholecystectomy, to prevent a future occurrence of common bile duct obstruction or other complications.

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Study Shows Bioluminescence Imaging Distinguishes Eye Tumors in Vivo, Leading to Early Treatment of Eye Cancer
At the moment, doctors rely on biopsy analysis to determine the progression of eye cancer. However, researchers now believe that a new technology, bioluminescence imaging (BLI), will allow doctors to detect tumors earlier and quickly choose a method of treatment that doesn't necessarily involve eye surgery. BLI is a new technology that uses the making and giving off of light by an organism to map diseases in a non-invasive way. Scientists have harnessed this technology to delicately detect and monitor various diseases, including eye cancer. BLI has several advantages over biopsy analysis, including in vivo monitoring, higher sensitivity, easier use and an overall more accurate correlation between cell numbers detected and tumor growth. A study detailed in the Association for Research in Vision and Ophthalmology's peer-reviewed Investigative Ophthalmology & Visual Science ("Non-invasive visualization of retinoblastoma growth and metastasis via bioluminescence imaging") shows how the researchers, led by Qian Huang, MD, PhD, of the First People's Hospital in Shanghai, China, were able to effectively create human eye tumors in mice using particular genes to label eye cancer. BLI was then performed on the mice using the NightOwl LB 981 Molecular Imaging System to monitor the growth and succession of these created tumors. "BLI allowed sensitive and quantitative localization and monitoring of intraocular and metastatic tumor growth in vivo and thus might be a useful tool to study cancer biology as well as anticancer therapies," said Huang. Eye cancer is the most common and aggressive form of cancer found in children under the age of 5. As with most cancers, locating the tumors during the early stages of the disease is key. "Eye removal is usually performed for larger tumors. Small tumors are treated using therapeutic approaches such as chemotherapy. Because of the fast progression, early detection is important for preservation of vision, eye retention and even survival," says Huang. Investigative Ophthalmology & Visual Science (IOVS) a peer-reviewed journal published monthly online and in print, IOVS publishes results from original hypothesis-based clinical and laboratory research studies. IOVS ranks No. 4 in Impact Factor among ophthalmology journals. The Association for Research in Vision and Ophthalmology (ARVO) is the largest eye and vision research organization in the world. Members include more than 12,500 eye and vision researchers from over 80 countries. The Association encourages and assists research, training, publication and knowledge-sharing in vision and ophthalmology.

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