Bile Composition in Healthy and Gallstones Patients

Gallbladder Bile Composition in Patients With Gallstones and Healthy Patients

Determine differences between lithogenic and non-lithogenic bile composition.

Study Overview

• Status: Unknown
• Conditions: Cholelithiasis; Gall Bladder Disease; Gall Stone
• Intervention / Treatment: Diagnostic test: Bile test; Diagnostic test: Blood test; Diagnostic test: Gall stone study; Diagnostic test: Microbiological bile test

Detailed Description

Gallstones constitute an entity known from antiquity, which have been found even in Egyptian mummies. In elder Greece, Tralliano discovered that gallstones are formed in the liver. Vesalio and Falopio described gallstones inside de gallbladder after a human body dissection and in 1882 Langenbuch performed the first cholecystectomy with good results, becoming the gold standard technique for cholelithiasis.

Nowadays, this pathology represents a public health problem in developed countries due to its high prevalence, which is getting higher, estimated between a 10 and a 15% of the population.

However, gallstones are asymptomatic in the 80% of the cases. In 5 years, a 10-20% of these patients will become symptomatic. The global risk of generating symptoms is about a 2% per year, meanwhile biliary tract complications in asymptomatic patients represent a 0'3% per year.

There are two main types of gallstones. The most common of them (70%) are cholesterol stones, composed of >50% of cholesterol. The other 30% are black pigment stones, with less than 20% of cholesterol in their composition.

The common ways on gallstone formation are: cholesterol supersaturation (due to a liver oversecretion); defects on gallbladder absorption, secretion and motility mechanisms; and higher percentage of deoxycholic acid in the biliary acids due to a slower intestinal movement. All of that leads to supersaturation and cholesterol nucleation.

Black pigment stones are formed of calcium bilirrubinate. The formation mechanism is not clearly defined, but there is an increment in not conjugated bilirubin levels, which is less soluble in water. These gallstones are more frequent in patients who show higher levels of this bilirubin, such as those with hemolysis, Gilbert syndrome or hereditary spherocytosis. They are also common in patients with Crohn disease (specially in those with ileal resection) and cystic fibrosis, in which exists an enterohepatic circulation alteration, driving to an increase on biliary salts and non-conjugated bilirubin levels.

Our work hypothesis is that bile composition in patients with gallstones on the gallbladder is different from those who doesn't show lithiasis.

• Study Type: Observational
• Enrollment (Anticipated): 62

Contacts and Locations

• Study Contact: Name: Alejandro Gil Catalán; Phone Number: 695621497; Email: alejandro.gil@ssib.es
• Study Contact Backup: Name: Francesc Xavier Molina Romero; Phone Number: 695621497; Email: xmolina@ssib.es

Study Locations

• Spain
  • Mallorca
    • Palma De Mallorca, Mallorca, Spain, 07010
      • Hospital Universitario Son Espases
      • Contact: Alejandro Gil Catalán; Phone Number: 695621497; Email: alejandro.gil@ssib.es

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 98 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

It includes patients who suffer from gallstones, which are operated for that reason (open or laparoscopic cholecystectomy), and patients who go through the same intervention for other reasons (cancer, organ donation)

Description

Inclusion Criteria for the Study Group:

1. Patients included for an elective cholecystectomy.
2. Normal hepatic and renal function.
3. Able to understand the nature of the study.
4. Wish to participate in the study and sign the informed consent.

Inclusion Criteria for the Control Group:

1. Patients included for an hepatectomy with gallbladder exeresis for surgery reasons, without lithiasis.
2. Patients included for peritoneal carcinomatosis surgery with gallbladder exeresis for surgery reasons, without lithiasis.
3. Organ donors.
4. Normal hepatic and renal function.
5. Able to understand the nature of the study.
6. Wish to participate in the study and sign the informed consent.

Exclusion Criteria:

1. Under 16 years old
2. Hepatic or renal insufficiency
3. Impossibility to understand the aim of the study

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Lithogenic bile in symptomatic patient; Patients who are performed a cholecystectomy as a treatment of their gallbladder disease	Diagnostic test: Bile test; Analyze bile components related to gall stones synthesis (cholesterol, bile acids, phospholypids, etc.); Diagnostic test: Blood test; Analyze blood components related to gall stones synthesis (cholesterol, bile acids, phospholypids, etc.); Diagnostic test: Gall stone study; Study of the extracted gall stones, analyzing their composition, type, etc.; Diagnostic test: Microbiological bile test; Determination of the microbiological composition of the bile
Lithogenic bile in asymptomatic patient; Patients who are performed a cholecystectomy for another reason (cancer, organ donation) and gall stones are found	Diagnostic test: Bile test; Analyze bile components related to gall stones synthesis (cholesterol, bile acids, phospholypids, etc.); Diagnostic test: Blood test; Analyze blood components related to gall stones synthesis (cholesterol, bile acids, phospholypids, etc.); Diagnostic test: Gall stone study; Study of the extracted gall stones, analyzing their composition, type, etc.; Diagnostic test: Microbiological bile test; Determination of the microbiological composition of the bile
Non-lithogenic bile; Patients who are performed a cholecystectomy for another reason (cancer, organ donation) without gall stones	Diagnostic test: Bile test; Analyze bile components related to gall stones synthesis (cholesterol, bile acids, phospholypids, etc.); Diagnostic test: Blood test; Analyze blood components related to gall stones synthesis (cholesterol, bile acids, phospholypids, etc.); Diagnostic test: Microbiological bile test; Determination of the microbiological composition of the bile

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences of bile composition between cases and controls	Bilirrubine in mg/dL	Intra-operatively

Collaborators and Investigators

• Sponsor: Hospital Son Espases

Publications and helpful links

General Publications

• Gibney EJ. Asymptomatic gallstones. Br J Surg. 1990 Apr;77(4):368-72. doi: 10.1002/bjs.1800770405.
• Heller F, Bouchier IA. Cholesterol and bile salt studies on the bile of patients with cholesterol gallstones. Gut. 1973 Feb;14(2):83-8. doi: 10.1136/gut.14.2.83.
• Jayanthi V, Sarika S, Varghese J, Vaithiswaran V, Sharma M, Reddy MS, Srinivasan V, Reddy GM, Rela M, Kalkura S. Composition of gallbladder bile in healthy individuals and patients with gallstone disease from north and South India. Indian J Gastroenterol. 2016 Sep;35(5):347-353. doi: 10.1007/s12664-016-0685-5. Epub 2016 Sep 16.
• Mackay C, Crook JN, Smith DC, McAllister RA. The composition of hepatic and gallbladder bile in patients with gallstones. Gut. 1972 Oct;13(10):759-62. doi: 10.1136/gut.13.10.759.
• Reinhold JG, Ferguson LK, Hunsberger A. THE COMPOSITION OF HUMAN GALLBLADDER BILE AND ITS RELATIONSHIP TO CHOLELITHIASIS. J Clin Invest. 1937 May;16(3):367-82. doi: 10.1172/JCI100864. No abstract available.
• Shaffer EA. Gallstone disease: Epidemiology of gallbladder stone disease. Best Pract Res Clin Gastroenterol. 2006;20(6):981-96. doi: 10.1016/j.bpg.2006.05.004.
• Van Erpecum KJ. Pathogenesis of cholesterol and pigment gallstones: an update. Clin Res Hepatol Gastroenterol. 2011 Apr;35(4):281-7. doi: 10.1016/j.clinre.2011.01.009. Epub 2011 Feb 25.

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2019
• Primary Completion (Anticipated): October 1, 2021
• Study Completion (Anticipated): June 1, 2022

Study Registration Dates

• First Submitted: June 4, 2019
• First Submitted That Met QC Criteria: June 7, 2019
• First Posted (Actual): June 10, 2019

Study Record Updates

• Last Update Posted (Actual): June 10, 2019
• Last Update Submitted That Met QC Criteria: June 7, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Urologic Diseases; Pathological Conditions, Anatomical; Biliary Tract Diseases; Calculi; Gallstones; Cholelithiasis; Cholecystolithiasis; Urinary Bladder Diseases; Gallbladder Diseases
• Other Study ID Numbers: BILISGILMOL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No