See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/342864641

Cholelithiasis: A Brief Review on Diagnostic Approach and Management in

Clinical Practice

Article · July 2020

DOI: 10.19080/ARGH.2020.15.555913

CITATION READS

1 3,109

2 authors, including:

Febyan Febyan
Orthopaedic & Traumatology - Prof Ngoerah General Hospital, Faculty of Medicine, Udayana University
52 PUBLICATIONS   21 CITATIONS   

SEE PROFILE

Some of the authors of this publication are also working on these related projects:

Semitendinosus and Gracilis Autograft for Neglected Patellar Tendon Rupture View project

All content following this page was uploaded by Febyan Febyan on 11 July 2020.

The user has requested enhancement of the downloaded file.

 Mini Review Adv Res Gastroentero Hepatol
Volume 15 Issue 3 - July 2020
DOI: 10.19080/ARGH.2020.15.555913 Copyright © All rights are reserved by Febyan

Cholelithiasis: A Brief Review on

Diagnostic Approach and Management in
Clinical Practice
Febyan1* and Ruswhandi2
1
Faculty of Medicine, Krida Wacana Christian University, Indonesia
2
Department of Internal Medicine, Army Gatot Soebroto Hospital, Indonesia
Submission: April 24, 2020; Published: July 07, 2020
*Corresponding author: Febyan, Medical Doctor, Faculty of Medicine, Krida Wacana Christian University, Jakarta, Indonesia

Abstract
Cholelithiasis is one of the most prevalent diseases in gastroenterology. There are many factors in cholelithiasis, such as genetic, lack of
physical activity, obesity, dietary, age, and other comorbidities. Commonly, cholelithiasis occurs asymptomatically; however, Murphy’s sign is one
of the most frequent pathognomonic findings in abdominal examination. Ultrasonography is known as the gold standard imaging examination in
diagnosing cholelithiasis. The management of cholelithiasis can be divided into two categories, such as medical treatment and surgical treatment,
which depends on the patient’s condition.
Keywords: Gallstones; Cholelithiasis; Adults; Ultrasonography; Urxodeoxycholic acid; Laparoscopic cholecystectomy; Open cholecystectomy;
Clinical practice
Abbreviations: UDCA: Ursodeoxycholic Acid; RCT: Randomized Controlled Trial; EASL: European Association for the Study of the Liver;
NSAIDs: Nonsteroidal Anti-Inflammatory Drugs; ERCP: Endoscopic Retrograde Cholangiopancreatography; CT: Computed Tomography; USG:
Ultrasonography; MRCP: Magnetic Resonance Cholangiopancreatography; WBC: White Blood Cell Count; CBC: Complete Blood Cell Count; RUQ:
Right Upper Quadrant

Introduction
[6]. This review is purposed to describe the diagnostic and
Cholelithiasis or gallstone is the presence of hardened
management of cholelithiasis in clinical practice.
deposits of digestive fluid that is formed in the gallbladder. The
gallbladder is a small organ located just beneath the liver. It holds Pathophysiology and Clinical Manifestation
the digestive fluid known as bile, which will be released into
Cholesterol gallstones are formed mainly due to over secretion
the small intestine [1]. Cholelithiasis affects approximately 5.3-
and saturation of cholesterol by liver cell; and hypomotility or
25% of the population, according to clinical survey reports from
impaired emptying of the gallbladder. In pigmented gallstones,
Europe, North and South America, and Asia [2,3]. Commonly,
conditions with high heme turnover, bilirubin may be present
this disorder occurs asymptomatically, and only 20% of people
in bile at higher than normal concentrations. Bilirubin may then
with cholelithiasis experience pain and complications. The most
crystallize and eventually forms stones [7]. The manifestation
common risk factor of cholelithiasis is gender, with females
of cholelithiasis is usually non-specific and not related to the
being one of the unmodifiable risk factors and is also related
presence of the gallstones. They include isolated heartburn, acid
to metabolic syndrome events [4]. Pimpale et al. [5] stated that
regurgitation, belching, nausea, vomiting, bloating, abdominal
cholelithiasis is commonly found in females in the 4th to 5th decade
distension, chest pain, postprandial fullness or early satiety, and
of life, with abdominal pain being the most typical symptom. There
flatulence [8]. Visceral pain originates from the impact of the
are some other risk factors of cholelithiasis, such as genetics, the
stone, or microlithiasis in the cystic duct or ampulla of Vater. This
lack of physical activity which is also associated with metabolic
condition leads to distension and contraction from the gallbladder
syndrome, obesity which is related to the increase of cholesterol
and the biliary tract. The intermittent increase of the pressure in
gallstones formation, dietary factors, and other comorbidities

Adv Res Gastroentero Hepatol 15(3): ARGH.MS.ID.555913 (2020) 00110

 Advanced Research in Gastroenterology & Hepatology

the gallbladder activates visceral sensory neurons. The pain will intestinal bleeding, in case where the symptoms of the occult or
be relieved if the stones move back into the gallbladder lumen, massive gastrointestinal bleeding are present [13,14].
passes through the ampulla into the duodenum, or moves back
Imaging tests
to the common bile duct. The pain will develop as an intense
and dull discomfort, either continuous or intermittent, with It is essential to have an accurate imaging modality
painful episodes ranging from hours to years [9]. During painful in cholelithiasis to ensure early intervention and prevent
episodes, some non-specific gastrointestinal symptoms may complications (bacterial infection of the gallbladder, perforation,
occur, including 60% of cases manifested as radiating pain to the etc.). Imaging modality also can prevent unnecessary treatment in
angle of the scapula or shoulder and less than 10% of cases to the event of false-positive findings. Some useful diagnostic tools
the retrosternal area. On the other hand, in two-thirds of patients are ultrasonography (USG), computed tomography (CT), magnetic
experience colicky pain that is associated with the urgency to resonance cholangiopancreatography (MRCP) [14].
walk, nausea and vomiting, as well as diaphoresis; and this type
Ultrasound is the method of choice and also known as the
of pain is usually not relieved by flatulence or bowel movements.
gold standard for diagnosing cholelithiasis. It is considered an
The presence of fever, persistent tachycardia, hypotension, or
excellent method because it has a precise diagnostic accuracy and
jaundice in clinical findings, requires a search for complications of
may be performed to examine nearly all organs of the abdomen,
cholelithiasis, including cholecystitis, cholangitis, pancreatitis, or
regardless of its noninvasiveness, lacking of ionizing radiation,
other systemic causes [10,11].
and relatively low cost. A study from Scruggs et al. found that
In physical examination, the signs may appear as the jaundice the USG also has a high sensitivity (97%) and specificity (93.6%)
and right upper quadrant (RUQ) tenderness during abdominal [15,16]. The previous study reported that one of the most
palpation. A positive Murphy’s sign may also be elicited. In important advantages of USG over other imaging techniques
emergency cases, the Charcot triad (fever, RUQ tenderness, and in the investigation of cholelithiasis is the ability to assess for
jaundice) can be found, and it strongly indicates the presence a sonographic Murphy’s sign, which is a reliable indicator of
of cholangitis, in which emergency treatment must be promptly cholelithiasis with sensitivity of 92%. A wall thickening of the
done to prevent the further complications [12]. gallbladder in the presence of gallstones by USG has a positive
predictive value of 95% for the diagnosis of cholelithiasis.
Diagnostic Approach Increased wall thickness of more than 3.5 mm is found to be a
Diagnosis of cholelithiasis is established by performing history reliable finding of cholelithiasis [17]. Pericholecystic fluid (fluid
taking, physical examination, blood examination, ultrasonography. around the gallbladder), distended gallbladder, edematous
gallbladder, and gall rocks also can be significantly generated
Laboratory tests on USG. Color circulation Doppler USG may show hyperemic,
Several laboratory tests should be considered in diagnosing pericholecystic blood flow, and acute inflammation. Visualization
cholelithiasis. A complete blood cell count (CBC) may show an of USG findings usually shows mobile echogenic foci casting
elevated white blood cell count (WBC), although a normal WBC posterior acoustic shadows (Figure 1), and sometimes a wall
result sometimes does not necessarily exclude the possibility in echo-shadow indication is observed if the gallbladder is full of
establishing the diagnosis. Other laboratory components include gallstones. This finding indicates cholelithiasis with cholecystitis
the liver function test, lipase, amylase, urinalysis, pregnancy test consist of gallbladder distension (> 40 mm) [18].
in women of childbearing age, and stool guaiac test to rule out of

Figure 1: Cholelithiasis by Ultrasonographic.

How to cite this article: Febyan, Ruswhandi. Cholelithiasis: A Brief Review on Diagnostic Approach and Management in Clinical Practice. Adv Res
00111
Gastroentero Hepatol, 2020;15(2): 555913. DOI: 10.19080/ARGH.2020.15.555913
 Advanced Research in Gastroenterology & Hepatology

Although cholescintigraphy also has both high sensitivity immediately and can confidently attribute localized pain to biliary
and specificity (96% and 90%, respectively) for the diagnosis of pathology [19]. For undefined cases, CT or MRCP is considered
cholelithiasis, this modality has several drawbacks that limit its as second-line modality that should be performed. Endoscopic
use in clinical practice. This method is unable to assess structures retrograde cholangiopancreatography (ERCP), endoscopic
outside of the biliary tract, and often lacks in readily available ultrasonography, percutaneous transhepatic cholangiography
equipment and personnel, full of radiation exposure, and takes are also recommended. The clinician needs to know about the
long hours to perform. It differs from USG that can be performed stepwise when undefined cases are found (Figure 2).

Figure 2: Flowchart for diagnosis of cholelithiasis [20].

Management to decrease biliary colic, with administration of UDCA for over 6

to 18 months at the dose of 8–10 mg/kg per day divided into 2
Medical treatment
to 3 times daily. The recurrence rate in patients who are treated
Treatment of colicky pain primarily involves pain control with with gallstone dissolution agents is 50% within five years [25].
nonsteroidal anti-inflammatory drugs (NSAIDs) or narcotic pain There are some side effects, including immune suppression,
relievers, and also may be accompanied by symptomatic treatment diarrhea, liver failure, portal hypertension, thrombocytopenia,
for nausea, vomiting, and fever as needed. Another option for pain and pruritus. Thus, the patients who are using UDCA should be
control is the anti-spasmodic agent (hyoscine-N-butyl bromide), monitored appropriately [26].
which is used to relax and relieve the spasms of the gallbladder.
Surgical treatment
However, comparison studies have shown that NSAIDs provide
faster and work more effectively as a pain reliever. The patient Surgical management for patients with symptomatic
should fast as part of the conservative management of colicky gallstones can be divided into two categories; (1) those who
pain and to avoid the release of endogenous cholecystokinin [20- have simple biliary colic and (2) those with complications.
22]. A study from the European Association for the Study of the Most patients with symptomatic gallstones can be treated
Liver (EASL) showed that the ursodeoxycholic acid (UDCA) is not using laparoscopic cholecystectomy. But Cochrane review of
indicated as a preventive medication for gallstone disease in the laparoscopic cholecystectomy versus open cholecystectomy
general population [23]. Otherwise, prophylactic UDCA (500 g/d) showed the similar results in complication rates and surgical time,
may prevent stone formation for those patients with post-bariatric but a shorter hospital stays (three fewer days; 95% CI, 2.3 to 3.9
surgery [23]. A randomized controlled trial (RCT) study published days) and shorter convalescence period (22 fewer days; 95% CI 8
in 2003 found a significantly reduced risk of gallstones formation to 37 days) [27]. Many factors that increase the risk of conversion
within 24 months after restrictive gastric bypass surgery (8% vs. to open cholecystectomy include male sex, age 60 years or
30%) [24]. older, previous upper abdominal surgery, thickened gallbladder
wall on ultrasonography, and acute cholecystitis [28]. Table 1
A study by Kotb (2012) reported that UDCA might also reduce
provides the indications and contraindications for laparoscopic
gallstones by the dissolution process in cholelithiasis patients
cholecystectomy.
that had confirmed by USG. Ursodeoxycholic acid has been shown

How to cite this article: Febyan, Ruswhandi. Cholelithiasis: A Brief Review on Diagnostic Approach and Management in Clinical Practice. Adv Res
00112
Gastroentero Hepatol, 2020;15(2): 555913. DOI: 10.19080/ARGH.2020.15.555913
 Advanced Research in Gastroenterology & Hepatology

Table 1: Indications and Contraindications of Laparoscopic Cholecystectomy [29].

Indications
Biliary dyskinesia, acute cholecystitis, gallstones (symptomatic or asymptomatic), complications related to common bile duct stones.
Contraindications
Absolute: uncontrolled coagulopathy, inability to tolerate general anesthesia, all types of gallbladder cancer.
Relative: severe acute peritonitis, septic shock, advanced cirrhosis/liver failure, previous upper abdominal surgeries, peritonitis.

Antibiotics pre-operation is not indicated in low-risk patients 11. Reshetnyak VI (2012) Concept of the pathogenesis and treatment of
undergoing elective surgery, but it may reduce the incidence of cholelithiasis. World J Hepatol 4(2): 18-34.

wound infection after laparoscopic cholecystectomy in high- 12. Gore JM (2013) Cholelithiasis. JAAPA 26(12): 54-55.
risk patients such as geriatric patient, comorbidities (diabetes 13. Thomas S (2013) Differentiating abdominal pain using Murphy’s sign.
mellitus, jaundice, cholangitis) [29,30]. The European Association Practice Nurs 24(3):141.
for the Study of the Liver recommends to limit the use of antibiotic 14. Aslam HM, Saleem S, Edhi MM (2013) Assessment of gallstone
prophylaxis to a single preoperative dose of intravenous cefazolin predictor: comparative analysis of ultrasonographic and biochemical
as much as 1 gram, given within one hour of skin excision [23]. parameters. Int Arc Med 6: 17.
15. Scruggs W, Fox JC, Potts B, Zlidenny A, McDonough J (2008) Accuracy
Conclusion of ED bedside ultrasound for identification of gallstones: retrospective
analysis of 575 studies. West J Emerg Med 9(1): 1-5.
In conclusion, cholelithiasis refers to the formation of
16. Gijaca V, Gurusamy KS, Takwoingi Y (2015) Endoscopic ultrasound
gallstones and may present with or without any obvious
versus magnetic resonance cholangiopancreatography for common
symptoms. Because cholelithiasis is a multifactorial disease, bile duct stones. Cochrane Database Syst Rev 15(2): CD011549.
prompt and structured diagnostic approaches, including history
17. Khan SP, Izhar S (2018) Ultrasound as a first line investigation of choice
taking, physical examination, laboratory tests, and imaging tests, in diagnosis acute cholicystitis. IJAR 6(11): 65-69.
should be performed to decide the management properly and
18. van Breda V, Engerbrecht MR, Smithuis RH, Puylaert JB (2007) Diffuse
minimize false-positive events. gallbladder wall thickening: differential diagnosis. AJR 188: 495-501.

References 19. Alobaide M, Gupta R, Jafri SZ, Fink-Bennet DM (2004) Current trends in
imaging evaluation of acute cholecystitis. Emer Radiol 10(5): 256-258.
1. Chung AY, Duke MC (2018) Acute biliary disease. Surg Clin North Am
98(5): 877-894. 20. Tazuma S, Unno M, Igarashi Y, Inui K, Uchiyama K, Kai M, et al (2017)
Evidence-based clinical practice guidelines for cholelithiasis 2016. J
2. Stinton LM, Myers RP, Shaffer EA (2010) Epidemiology of gallstones. Gastroenterol 52(3): 276-300.
Gastroenterol Clin North Am 39(2): 157-169.
21. Henderson SO, Swadron S, Newton E (2022) Comparison of intravenous
3. Festi D, Reggiani MLB, Attili AF (2010) Natural history of gallstone ketorolac and meperidine in the treatment of biliary colic. J Emerg Med
disease: Expectant management or active treatment? Results from a 23(3): 237-241.
population-based cohort study. J Gastroenterol Hepatol 25(4): 719-
724. 22. Kumar A, Deed JS, Bhasin B, Kumar A, Thomas S (2004) Comparison
of the effect of diclofenac with hyoscine-N-butylbromide in the
4. Cojocaru DC, Mitu F, Dascalu CG, Manole A, Cozma CD (2014) The symptomatic treatment of acute biliary colic. ANZ J Surg 74(7): 573-
predictor of cholelithiasis in female patients with metabolic syndrome. 576.
Cent. Eur J Med 9(1): 108-114.
23. European Association for the Study of the Liver (2016) EASL clinical
5. Pimpale R, Katakwar P, Akhtar M (2019) Cholelithiasis: causative practice guidelines on the prevention, diagnosis and treatment of
factors, clinical manifestations and management. Int Surg J 6(6): 2133- gallstones. Journal of Hepatology 65: 146-181.
2138.
24. Gutt C, Schlafer S, Lammert F (2020) The treatment of gallstone
6. Peswani AR, Sequeira VJ, D’silva M, Ghanwat S, Shah PP, Pinto AC (2019) disease. Dtsch Arztebl Int 117(9): 148-158.
Association between gallstone disease and metabolic syndrome. IJCMR
6(10): J1-J5. 25. Kotb MB (2012) Molecular mechanism of ursodeoxycholic acid toxicity
& side effects: ursodeoxycholic acid freezes regeneration & induces
7. Chen Y, Kong J, Wu S (2015) Cholesterol gallstone disease: focusing on hibernation mode. Int J Mol Sci 12(7): 8882-8914.
the role of gallbladder. Laboratory Investigation 95: 124-131.
26. Guarino MP, Cocca S, Altomare A, Emerenziana S, Cicala M (2013)
8. Lammert F, Gurusamy K, Ko CW (2016) Gallstones. Nat Rev Dis Primers Ursodeoxycholic acid therapy in gallbladder disease, a story not yet
2:16025. completed. World J Gastroenterol 19(31): 5029-5034.
9. Shabanzadeh DM (2018) Incidence of gallstone disease and 27. Keus F, de Jong JA, Gooszen HG, van Laarhiven CJ (2006) Laparoscopic
complications. Curr Opin Gastroenterol 34(2): 81-89. versus open cholecystectomy for patients with symptomatic
cholecystolithiasis. Cochrane Database Syst Rev 4: CD006231.
10. Portincasa P, Moschetta A, Palasciano G (2006) Cholesterol gallstone
disease. Lancet 368(9531): 230-239.

How to cite this article: Febyan, Ruswhandi. Cholelithiasis: A Brief Review on Diagnostic Approach and Management in Clinical Practice. Adv Res
00113
Gastroentero Hepatol, 2020;15(2): 555913. DOI: 10.19080/ARGH.2020.15.555913
 Advanced Research in Gastroenterology & Hepatology

28. Tayeb M, Raza SA, Khan MR, Azami R (2005) Conversion from 30. Manes G, Paspatis G, Aabakken L, Anderloni A, Arvanitakis M, Ah-
laparoscopic to open cholecystectomy: multivariate analysis of Saune P (2019) Endoscopic management of common bile duct stone:
preoperative risk factors. J Postgrad Med 51(1): 17-20. European society of gastrointestinal endoscopy (ESGE) guideline.
Endoscopy 51(5): 472-491.
29. Peitzman AB, Watson GA, Marsh JW (2014) Acute cholecystitis: when
to operate and how to do it safely. J Trauma Acute Care Surg 78(1):
1-12.

This work is licensed under Creative

Commons Attribution 4.0 License
Your next submission with JuniperPublishers
DOI:10.19080/ARGH.2020.15.555913 will reach you the below assets
• Quality Editorial service
• Swift Peer Review
• Reprints availability
• E-prints Service
• Manuscript Podcast for convenient understanding
• Global attainment for your research
• Manuscript accessibility in different formats
( Pdf, E-pub, Full Text, audio)
• Unceasing customer service

Track the below URL for one-step submission

https://juniperpublishers.com/online-submission.php

How to cite this article: Febyan, Ruswhandi. Cholelithiasis: A Brief Review on Diagnostic Approach and Management in Clinical Practice. Adv Res
00114
Gastroentero Hepatol, 2020;15(2): 555913. DOI: 10.19080/ARGH.2020.15.555913

View publication stats