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Choledocholithiasis

Choledocholethiasis, or bile duct stones, refers to the presence of stones in bile duct. These stones usually form in the gall bladder and then migrate to the bile duct.


Presentation

In most of the cases, the patient remains asymptomatic with the stones passing to the duodenum or even when remaining within the duct. When the stones obstruct the duct, a number of clinical manifestations results. Colicky pain in the upper right quadrant, particularly after cholecystectomy, is the most common symptom of choledochothiasis. The pain may be sporadic and may spread to the right scapular tip [6]. The pain usually commences within 5 to 60 min after a fatty meal. The dull, intense pain may increase for few minutes and then reduce gradually. If the disease progresses to cholangitis, fever, chills, jaundice and increased serum levels of alkaline phosphatase and transaminases ensue. Ascending cholangitis may also lead to sepsis, requiring immediate drainage of bile duct and antibiotic treatment. Tachycardia and hypotension are also common among patients with ascending cholangitis.

Fever
  • By comparing them, was observed that fever and jaundice were the signs and symptoms with statistical significance.[ncbi.nlm.nih.gov]
  • Abstract A 67-years-old male presented with periumbilical abdominal pain, fever and jaundice. His anaerobic blood culture was positive for clostridium perfringens.[ncbi.nlm.nih.gov]
  • An 8-month-old girl presented with high fever and obstructive jaundice. Ultrasound scan showed acute cholecystitis with stones in the bile duct. After 2-week-long antibiotic therapy the acute cholecystitis and hepatic impairment resolved.[ncbi.nlm.nih.gov]
  • Fever and rigors may be present if there is an associated ascending cholangitis. Patients with symptoms or signs suggestive of bacterial cholangitis (fever or shaking chills in addition to cholestasis) should be hospitalized.[hepatitis.va.gov]
  • Usually have abnormalities in liver enzymes and pain but no fever. The 2 major complications are 1) Cholangitis and 2) Acute pancreatitis.[sketchymedicine.com]
Chills
  • […] cholelithiasis ) in the common bile duct. choledocholithiasis choledocholithiasis Common bile duct stone(s) GI disease The presence of gallstones in the common bile duct, which occurs in 15% of Pts with gallstones Clinical Abdominal pain, N&V; if severe, fever, chills[medical-dictionary.thefreedictionary.com]
  • Patients with symptoms or signs suggestive of bacterial cholangitis (fever or shaking chills in addition to cholestasis) should be hospitalized.[hepatitis.va.gov]
  • […] an ED visit with reported subjective fever; exam, however, was not consistent with cholangitis Recall that cholangitis is one of the most dangerous complications of CBD stones Acute cholangitis involves biliary pain, jaundice, and spiking fevers with chills[errolozdalga.com]
  • Fever with chills would indicate cholangitis. Pruritus and clay colored stools may be present if biliary obstruction is high grade. Fever and icterus may be present on general examination.[speciality.medicaldialogues.in]
  • Jaundice: Fever: Chills and fever are usually asociated with pain abdomen. Other symptoms: clay color stool. Dark urine. Symptoms associated with Pancreatitis. Charcot's Triad: [ edit ] Clasically seen in common-bile-duct-stone .[en.wikibooks.org]
Abdominal Pain
  • OBJECTIVES: Although abdominal pain is a cardinal feature of choledocholithiasis, there has been little formal study of the features of pain in this condition.[ncbi.nlm.nih.gov]
  • Abdominal pain disappeared immediately after EPBD, and she resumed oral intake 2 days after EPBD. In conclusion, EPBD may be a safe and effective technique for the treatment of choledocholithiasis in pediatric patients.[ncbi.nlm.nih.gov]
  • Abstract A 67-years-old male presented with periumbilical abdominal pain, fever and jaundice. His anaerobic blood culture was positive for clostridium perfringens.[ncbi.nlm.nih.gov]
  • Upper abdominal pain in any patient with a history of surgery for duodenal atresia in the past warrants a thorough evaluation for any biliary tract anomaly, cholecystitis, cholangitis, cholelithiasis or choledocholithiasis.[ncbi.nlm.nih.gov]
  • Abdominal pain, biliary disorders, and acute pancreatitis are frequently observed but malignant degeneration is rare. A 70-year-old man had a history of epigastralgia associated with abnormal liver function tests suggesting gallstones.[ncbi.nlm.nih.gov]
Vomiting
  • She had vomiting at 157 days of age. Ultrasonography revealed calculi in the gallbladder and a dilated common bile duct.[ncbi.nlm.nih.gov]
  • In this case, a 75-year-old female was admitted to our hospital presented with epigastric pain and vomiting for one day. Abdominal computed tomography revealed dilated common bile duct, pancreatitis and peripancreatic effusion.[ncbi.nlm.nih.gov]
  • Associated symptoms of nausea (69.2%) and vomiting (30.7%) were common. No differences in pain characteristics were detected between those with or without a prior cholecystectomy.[ncbi.nlm.nih.gov]
  • Fever Jaundice, or yellowing of skin and whites of the eyes Loss of appetite Nausea and vomiting Clay-colored stools Blockage and infection caused by stones in the biliary tract can be life-threatening.[wexnermedical.osu.edu]
  • The pain lasts longer than 6h and is usually associated with nausea/vomiting, fever and right upper quadrant pain. Choledocholithiasis – gallstones in the common bile duct .[sketchymedicine.com]
Nausea
  • Associated symptoms of nausea (69.2%) and vomiting (30.7%) were common. No differences in pain characteristics were detected between those with or without a prior cholecystectomy.[ncbi.nlm.nih.gov]
  • METHODS: The patient was admitted to the Department of Gastroenterology because of fatigue and nausea, with concomitant elevation of alanine aminotransferase (ALT), 550 U/L, and asparagine aminotransferase (AST), 300 U/L.[ncbi.nlm.nih.gov]
  • Acute cholecystitis Colicky pain in right upper quadrant and right lower scapula; nausea, vomiting; low-grade fever. Chronic cholecystitis Anorexia, flatulence, nausea, fat intolerance; episodic or diffuse abdominal pain, heartburn.[medi-info.com]
  • Nausea is frequent. They may also give a history of prior intermittent RUQ pain, precipitated by fatty meals. Note that presentation may be atypical in older patients and pain may be absent. Jaundice may be present, but is not a cardinal sign.[hepatitis.va.gov]
  • Symptomatic Medications: - Hydroxyzine ( Vistaril) 25-50 mg IV/IM q4-6h prn MS, nausea. -Omeprazole (Prilosec) 20 mg PO bid OR - Famotidine ( Pepcid) 20 mg IV/PO q12h. -Heparin 5000 U SQ q12h OR -Enoxaparin (Lovenox) 30 mg SQ q12h. 11.[fprmed.com]
Colic
  • It’s biliary colic that just doesn’t go away. The pain lasts longer than 6h and is usually associated with nausea/vomiting, fever and right upper quadrant pain. Choledocholithiasis – gallstones in the common bile duct .[sketchymedicine.com]
  • METHODS: Patients with biliary colic or acute biliary pancreatitis, who were referred for suspected choledocholithiasis on the basis of alterations in liver function tests were prospectively included over 12 months period in blinded randomized fashion[ncbi.nlm.nih.gov]
  • Biliary dyskinesia includes motility disorders resulting in biliary colic in the absence of gallstones. Copyright 2017 Elsevier Inc. All rights reserved.[ncbi.nlm.nih.gov]
  • Background: Complications of common bile duct stones (choledocholithiasis) can vary from simple biliary colic to lifethreatening conditions.[ncbi.nlm.nih.gov]
  • The results showed that the total bilirubin, alanine aminotransferase, common bile duct diameter, number of stones, size of the smallest calculus, biliary colic, acute cholecystitis and pancreatitis had the best prognostic value of CBDS.[ncbi.nlm.nih.gov]
Clay-Colored Stool
  • Clay-colored stool – the characteristic brownish color of the stool is given to it by the bile. If the bile is not reaching the small intestine, the stool may become clay-colored.[ahealthgroup.com]
  • Fever Jaundice, or yellowing of skin and whites of the eyes Loss of appetite Nausea and vomiting Clay-colored stools Blockage and infection caused by stones in the biliary tract can be life-threatening.[wexnermedical.osu.edu]
  • Fever Yellowing of skin and whites of the eyes (jaundice) Loss of appetite Nausea and vomiting Clay-colored stools The goal of treatment is to relieve the blockage.[nlm.nih.gov]
  • Jaundice with or without cholestatic features like pruritus and clay colored stools, fever with chills due to cholangitis, acute pancreatitis may also form part of history. (Physical examination is usually non-contributory).[speciality.medicaldialogues.in]
Jaundice
  • By comparing them, was observed that fever and jaundice were the signs and symptoms with statistical significance.[ncbi.nlm.nih.gov]
  • , Obstructive Jaundice) Progression of Common Bile Duct Stone (Choledocholithiasis, Cholangitis, Obstructive Jaundice) Symptoms of Common Bile Duct Stone (Choledocholithiasis, Cholangitis, Obstructive Jaundice) Clinical Examination of Common Bile Duct[myvmc.com]
  • Abstract We report a case of 26-year-old woman at 10th week of gestation with cholestatic jaundice due to a common bile duct (CBD) stone managed by endoscopical retrograde cholangiopancreatography (ERCP).[ncbi.nlm.nih.gov]
  • Using ultrasonogram and magnetic resonance cholangiopancreatography (MRCP), we diagnosed cholelithiasis and choledocholithiasis in a premature and low birth weight infant who was admitted to the hospital with complaints of obstructive jaundice and alcoholic[ncbi.nlm.nih.gov]
Biliary Colic
  • It’s biliary colic that just doesn’t go away. The pain lasts longer than 6h and is usually associated with nausea/vomiting, fever and right upper quadrant pain. Choledocholithiasis – gallstones in the common bile duct .[sketchymedicine.com]
  • METHODS: Patients with biliary colic or acute biliary pancreatitis, who were referred for suspected choledocholithiasis on the basis of alterations in liver function tests were prospectively included over 12 months period in blinded randomized fashion[ncbi.nlm.nih.gov]
  • Biliary dyskinesia includes motility disorders resulting in biliary colic in the absence of gallstones. Copyright 2017 Elsevier Inc. All rights reserved.[ncbi.nlm.nih.gov]
  • Background: Complications of common bile duct stones (choledocholithiasis) can vary from simple biliary colic to lifethreatening conditions.[ncbi.nlm.nih.gov]
  • The results showed that the total bilirubin, alanine aminotransferase, common bile duct diameter, number of stones, size of the smallest calculus, biliary colic, acute cholecystitis and pancreatitis had the best prognostic value of CBDS.[ncbi.nlm.nih.gov]
Murphy's Sign
  • Symptoms During physical examination , Murphy’s sign is usually negative , which helps to distinguish choledocholithiasis from cholecystitis .[ahealthgroup.com]
  • Signs and symptoms [ edit ] 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.[en.wikipedia.org]
  • 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.[en.wikipedia.org]
  • The positive predictive value (PPV) of the presence of stones and a positive Murphy’s sign has been reported to be 92%. The PPV of stones and GB wall thickening has been reported to be 95%.[cdemcurriculum.org]
  • sign), palpable gallbladder, mild jaundice Abdominal tenderness, abnormal liver chemistries or amylase/lipase Other features Obstructive jaundice,intermittent elevation of liver chemistries Cholestasis, leucocytosis, positive blood cultures Cholestasis[clinicaladvisor.com]
Scleral Icterus
  • Scleral icterus may be present, but is not a reliable sign. In case of cholangitis, fever, tachycardia and hypotension may be present.[hepatitis.va.gov]
  • icterus, dark urine, acholic stool), cholangitis (fever, abdominal pain, jaundice, hypotension, mental status changes), and pancreatitis (constant epigastric pain radiating to the back, nausea, vomiting, anorexia).[clinicaladvisor.com]
Hepatomegaly
  • His abdomen was soft and lax, mildly distended with hepatomegaly about 4 cm below the costal margin, round edge, firm, not tender with a span of 8.5 cm, with no other significant findings on examinations.[saudisurgj.org]
Pruritus
  • A 57-year-old Japanese man who had undergone LC 6 years previously was referred to our hospital with pruritus and jaundice.[ncbi.nlm.nih.gov]
  • Jaundice with or without cholestatic features like pruritus and clay colored stools, fever with chills due to cholangitis, acute pancreatitis may also form part of history. (Physical examination is usually non-contributory).[speciality.medicaldialogues.in]
Dark Urine
  • Dark urine. Symptoms associated with Pancreatitis. Charcot's Triad: [ edit ] Clasically seen in common-bile-duct-stone . Fluctuating Jaundice Pain RUQ Fever ( with rigors ) Examination: [ edit ] O/E: Icterus ( ). Febrile. P/A: RUQ tenderness. NB ![en.wikibooks.org]
  • urine and acholic stool can be seen in complete or near-complete biliary obstruction.[clinicaladvisor.com]
  • urine for 4 days.[saudisurgj.org]
  • Clinical presentation Jaundice White coloured stools Dark urine Scratch marks in body Yellowish discolouration of sclera, nail bed Tender right upper quadrant, Palpable gall bladder /- 15.[de.slideshare.net]

Workup

Choledocholethiasis is often diagnosed based on a clinical suspicion rather than a specific manifestation. Complete blood picture is a general laboratory procedure suggested for suspected gallstones and an elevated white blood cell count suggests infection as in cholangitis and pancreatitis. Hyperbilirubinemia and elevated serum alkaline phosphatase can be noted in liver function tests and indicate intraductal bile stasis. These results often warrant further investigation, particularly imaging studies.

Transabdominal ultrasonography is the most common imaging method for detecting gallstones. In choledocholethiasis, ultrasonography may reveal dilatation of the duct, an indicator of duct obstruction. Endoscopic ultrasonography is specific in 95% of the patients and sensitive in 94% of the patients in detecting bile duct stones. But this procedure requires special skill and expertise. Endoscopic retrograde cholangiopancreatography (ERCP) is useful in diagnosis and management of stones in common bile duct. It is usually performed in combination with sphincterotomy [7]. Magnetic resonance cholangiopancreatography is a technique with 93% specificity and 94% sensitivity in detecting bile duct stones and useful in detecting stones that are missed in ultrasonography. This method is often the confirmatory in diagnosis and can be used for directing a patient for therapeutic ERCP. In patients where ERCP is difficult, percutaneous transhepatic cholangiography is recommended. This is particularly true of patients who had bile duct stones previously.

Left Pleural Effusion
  • A 55-year-old female patient presented in the emergency department with features of septicaemia with left pleural effusion. Intercostal tube drainage drained 5 L of bile on the first day and around 500-600 mL of bile each day subsequently.[ncbi.nlm.nih.gov]
Alkaline Phosphatase Increased
  • Pathophysiology [ edit ] This obstruction may lead to jaundice, elevation in alkaline phosphatase , increase in conjugated bilirubin in the blood and increase in cholesterol in the blood.[en.wikipedia.org]
  • 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.[en.wikipedia.org]
Clostridium Perfringens
  • His anaerobic blood culture was positive for clostridium perfringens. Computed tomogram scan of the abdomen and abdominal ultrasound showed normal gallbladder and common bile duct (CBD).[ncbi.nlm.nih.gov]
Lymphocytic Infiltrate
  • RESULTS: Liver biopsy showed diffuse lymphocyte infiltration in the dilated portal spaces without lesion of hepatic lobules. Several weeks after stopping agomelatine, the liver enzymes returned to normal.[ncbi.nlm.nih.gov]

Treatment

ERCP, with spnincterotomy in conjunction with gallstone removal, is the treatment of choice in most of the cases of choledocholethiasis [8]. This helps in reducing the pressure and to drain the biliary tree. Those with severe symptoms, as in cholangitis, may require antibiotics treatment with ERCP. This procedure has reduced the need for a surgical procedure by 0.2%.

Dissolution is an option in patients with asymptomatic duct stones. Those who have symptomatic bile duct stones, should consult for both surgical and non-surgical options. Dissolution may be considered in many cases, particularly in those where surgery may be a risk. Dissolution therapy is suggested in patients with functioning gallstone, but with multiple gallstones that are radiolucent. Contact dissolution, oral bile salt therapy, and lithotripsy are some of the dissolution methods used. The presence of multiple stones increases the surface area for contact with the dissolution agent. Patients who are resistant to endoscopic removal may opt for lithotripsy.

Those who have choledocholethiasis and gallstones, may opt for cholecystectomy. Intraoperative cholangiography is performed along with cholecystectomy to remove stones from the bile duct. Choledochoduodenostomy, in which a fistula between bile duct and adjacent duodenum allows the passage of stone into the proximal part of intestine, may also be used. Laparoscopic cholecystectomy is a less invasive procedure for removing stones from the duct and gallbladder [9]. Cholecystostomy is performed by radiologists under a CT scan guidance to place a drainage tube in the gallbladder [10]. This method helps to improve the symptoms by draining the bile.

Prognosis

Choledocholethiasis is not associated with increased mortality or morbidity. About half of the patients with this condition remain asymptomatic, but some of the complications may require immediate treatment or can become life threatening. Cholangitis is a complication that may require immediate treatment. If left untreated it may be fatal for the patient. Pancreatitis is another severe complication that requires immediate attention.

Etiology

Pathogenesis and risk factors of choledocholethiasis vary with the type of stone. Secondary stones are mostly cholesterol gallstones that form in the gallbladder and then migrate to the bile duct. Obesity, pregnancy, gallbladder stasis, certain medications and some genetic factors increase the risk of developing choledocholethiasis. Metabolic syndrome leads to increased secretion of cholesterol and thus elevates the risk of developing this condition. Increased levels of progesterone may lead to gallbladder stasis, allowing concentration of bile. Injuries of spinal cord, sudden weight loss with severe diet restriction, and prolonged parenteral nutrition also cause gallbladder stasis. Certain medications tend to increase secretion of cholesterol in bile while some others decrease the emptying of gallbladder, both increasing the risk of developing gallstones. Estrogen, fibrate hypolipidemic drugs and somatostatins increase the risk of gallstones by these methods. Certain genes are also linked to increased risk of choledocholethiasis [2].

Pigmented stones form when there is intraductal stasis of bile. Patients with biliary strictures after surgery or choledochal cysts have reduced mobility of the bile in the ducts with bacterial colonization. Both the conditions favor development of gall stones in the duct. Those who have increased rate of hemolysis have high turnover of heme and intraductal stasis, and develop black or brown pigmented gallstones. Patients with sickle cell anemia, beta-thalassemia, and spherocytosis have increased hemolysis and thus increased risk of pigmented, primary stones. Infestation of biliary flukes lead to the formation of biliary strictures, favoring formation of pigmented stones. These stones are most commonly seen in East Asia where biliary fluke infestation is prevalent. Diseases affecting reabsorption of bile salts, including Crohn disease and ileal resection, increase the risk of gall stones.

Epidemiology

About 70-80% of cases are caused by secondary stones that develop in the gallbladder and then move to the bile ducts. It is interesting to note that about 15% of the patients with cholecystolithiasis have stones in bile ducts and around 80%-95% of the patients with choledocholethiasis have stones in the gallbladder.

A number of factors, including ethnicity, comorbidities, gender and genetics, affect the prevalence of this condition. In general, around 20% of the population have gallstones. The prevalence is found to be lower in Asia and Africa [3]. Frequency of bile duct stones increases with age. It was found to range from 5% in 30 year old to 50% in people in the age group of 75 to 80 years. About 60% of the patients above the age of 60 years who undergo cholecystectomy develop gallstones. Presence of stones in children is rare, other than in those having congenital disorders. Incidence of gall stones is 2-3 times more among women when compared to men and this may be attributed to the presence of hormone estrogen [4]. Native American population, Hispanics and North European population have an increased incidence of gallstones [5].

Sex distribution
Age distribution

Pathophysiology

When bile concentrates in the gallbladder or the duct, it results in the precipitation and crystallization of certain components, forming stones. Crystals in the bladder or duct may get entrapped in the mucus forming sludge. Stones may grow or fuse with other stones to form larger gallstones. Complications arise when these stones obstruct the ducts and gallbladder.

One of the major component that leads to the formation of stones is cholesterol. When the proportion of this substance increases beyond normal in the bile, it becomes saturated with cholesterol leading to the formation of cholesterol monohydrate crystals. Factors that determine the formation of cholesterol stones are:

  • Amount of cholesterol secreted in the bile 
  • Degree of concentration of bile
  • Extent of bile stasis

During severe hemolysis, concentration of bilirubin in the bile increases considerably, resulting in crystallization of calcium bilirubinate which over a period of time oxidizes and forms dark colored stones. Bacterial infection also lead to crystallization of bilirubin in the bile. Calcium precipitates formed by bacterial infection are dark brown in color and are mostly formed in the bile ducts. Infection of the cholesterol stones with bacteria may cause mucosal inflammation in the gallbladder. In some cases, these stones may accumulate calcium salts or calcium bilirubinate forming mixed stones. These stones may be large and are usually visible in X-ray imaging.

Prevention

Gall stones can be prevented using ursodeoxycholic acid, particularly in high-risk conditions. The recommended dose is 60mg/day. Diet containing less fat is also a good step to decrease the chances of gall stones. Patients who had choledocholethiasis once have chances of recurrence. Moderate physical activity and diet with increased content of fiber and lesser saturated fat reduce the risk of stones in gall bladder.

Summary

Choledocholethiasis, or bile duct stones as they are commonly known as, refers to the presence of gallstones in common bile duct. These stones may lead to cholangitis, biliary obstruction, biliary colic or pancreatitis. Some patients may be asymptomatic as the stones pass into the duodenum or remain in the duct. Stones found in the duct may be of classified into:

  • Primary stones (form in the bile duct)
  • Secondary stones (form in gall bladder and then move into the duct)
  • Residual stones (stones left over after cholecystectomy)
  • Recurrent stones (form 3-4 years after the surgery)

Gallstones are common in the general population, and about 8-10% of the people with gallstones develop choledocholethiasis. It is more prevalent among patients who undergo cholecystectomy [1]. Choledocholethiasis usually occurs due to the passage of gallstones from the gallbladder to the common bile duct. This passage may obstruct the flow of bile and result in biliary colic. And if the obstruction persists, it may lead to inflammation of the gallbladder. Stagnation of bile in the duct may result in infection of the duct, cholangitis. Treatment of the disease depends on severity. Surgical intervention may be needed if obstruction is symptomatic.

Patient Information

Choledocholethiasis, or bile duct stones, refers to the presence of stones in the bile duct. These stones usually form in the gallbladder and then migrate to bile duct. In some cases, stones may form in the duct directly. About 15% of the people who have gallstones develop bile duct stones. Gallstones are generally formed from two components in bile – cholesterol and pigments. These stones may block the duct and result in jaundice. In some cases the stone may move into the intestine without causing any further complications. Some of the factors that increase the risk of developing duct stones include high serum cholesterol levels, increased age, obesity, rapid loss of weight, and parenteral nutrition. Some hereditary diseases which result in hemolysis may also lead to the formation of stones in the gallbladder and ducts.

As bile is blocked in the duct, it leads to jaundice and other complications. If the bile is stagnant in the duct, it may lead to infection and affect other organs like liver and pancreas. With the progression of the disease, liver may undergo fibrosis resulting in cirrhosis. Stones in the bile duct may or may not cause any symptoms. If the bile duct is blocked, it may cause pain in the upper middle part of the abdomen. Fever, jaundice, loss of appetite and vomiting are some other common symptoms of this condition. If bacterial infection occurs in the stagnant bile, it may spread rapidly and lead to life threatening situation.

Blood tests, liver function tests, CT scan and ultrasound are some of the tests useful in detecting the presence of stones in the bile duct. Blood tests are useful in checking for infection and to understand the functioning of liver and pancreas. Relieving the blockage from the duct is the main focus of any treatment modality. Non-surgical methods of treating this condition include dissolution with medication and fragmentation using lithotripsy. Surgery is used to remove stones from gall and also from the ducts. In some cases a small cut is made in the duct to help them pass into the intestine or to remove them. Stenting the duct also helps to keep the lumen open for the passage of the bile. Moderate physical activity and changes in the diet with less of saturated fats may help in preventing choledocholethiasis.

References

Article

  1. Cronan JJ. US diagnosis of choledocholithiasis: a reappraisal. Radiology. 1986;161 (1): 133-4.
  2. Portincasa P, Moschetta A, Palasciano G. Cholesterol gallstone disease. Lancet. 2006;368(9531):230-9.
  3. Halldestam I, Kullman E, Borch K. Incidence of and potential risk factors for gallstone disease in a general population sample. Br J Surg. 2009;96(11):1315-22.
  4. Wang HH, Liu M, Clegg DJ, Portincasa P, Wang DQ. New insights into the molecular mechanisms underlying effects of estrogen on cholesterol gallstone formation. Biochim Biophys Acta. 2009;1791(11):1037-47.
  5. Shaffer EA. Epidemiology and risk factors for gallstone disease: has the paradigm changed in the 21st century?. Curr Gastroenterol Rep. 2005;7(2):132-40.
  6. Gilani SN, Bass G, Leader F, Walsh TN. Collins' sign: validation of a clinical sign in cholelithiasis. Ir J Med Sci. 2009; 178(4):397-400. 
  7. NIH state-of-the-science statement on endoscopic retrograde cholangiopancreatography (ERCP) for diagnosis and therapy. NIH Consens State Sci Statements. 2002;19(1):1-26.
  8. Sugiyama M, Suzuki Y, Abe N et-al. Endoscopic retreatment of recurrent choledocholithiasis after sphincterotomy. Gut. 2004;53 (12): 1856-9.
  9. Binenbaum SJ, Teixeira JA, Forrester GJ, Harvey EJ, Afthinos J, Kim GJ, et al. Single-incision laparoscopic cholecystectomy using a flexible endoscope. Arch Surg. 2009;144(8):734-8.
  10. Schirmer BD, Winters KL, Edlich RF. Cholelithiasis and cholecystitis. J Long Term Eff Med Implants. 2005;15(3):329-38.

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Last updated: 2018-06-22 04:40