*Corresponding author:Febyan, Medical Doctor, Faculty of Medicine, Krida Wacana Christian University, Jakarta, Indonesia
How to cite this article:Febyan, Ruswhandi. Cholelithiasis: A Brief Review on Diagnostic Approach and Management in Clinical Practice. Adv Res
Gastroentero Hepatol, 2020;15(2): 555913. DOI: 10.19080/ARGH.2020.15.555913.
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
Cholelithiasis or gallstone is the presence of hardened deposits of digestive fluid that is formed in the gallbladder. The gallbladder is a small organ located just beneath the liver. It holds the digestive fluid known as bile, which will be released into the small intestine . Cholelithiasis affects approximately 5.3-25% of the population, according to clinical survey reports from Europe, North and South America, and Asia [2,3]. Commonly, this disorder occurs asymptomatically, and only 20% of people with cholelithiasis experience pain and complications. The most common risk factor of cholelithiasis is gender, with females being one of the unmodifiable risk factors and is also related to metabolic syndrome events . Pimpale et al.  stated that cholelithiasis is commonly found in females in the 4th to 5th decade of life, with abdominal pain being the most typical symptom. There are some other risk factors of cholelithiasis, such as genetics, the lack of physical activity which is also associated with metabolic syndrome, obesity which is related to the increase of cholesterol gallstones formation, dietary factors, and other comorbidities
. This review is purposed to describe the diagnostic and management of cholelithiasis in clinical practice.
Cholesterol gallstones are formed mainly due to over secretion and saturation of cholesterol by liver cell; and hypomotility or impaired emptying of the gallbladder. In pigmented gallstones, conditions with high heme turnover, bilirubin may be present in bile at higher than normal concentrations. Bilirubin may then crystallize and eventually forms stones . The manifestation of cholelithiasis is usually non-specific and not related to the presence of the gallstones. They include isolated heartburn, acid regurgitation, belching, nausea, vomiting, bloating, abdominal distension, chest pain, postprandial fullness or early satiety, and flatulence . Visceral pain originates from the impact of the stone, or microlithiasis in the cystic duct or ampulla of Vater. This condition leads to distension and contraction from the gallbladder and the biliary tract. The intermittent increase of the pressure in the gallbladder activates visceral sensory neurons. The pain will
be relieved if the stones move back into the gallbladder lumen,
passes through the ampulla into the duodenum, or moves back
to the common bile duct. The pain will develop as an intense
and dull discomfort, either continuous or intermittent, with
painful episodes ranging from hours to years . During painful
episodes, some non-specific gastrointestinal symptoms may
occur, including 60% of cases manifested as radiating pain to the
angle of the scapula or shoulder and less than 10% of cases to
the retrosternal area. On the other hand, in two-thirds of patients
experience colicky pain that is associated with the urgency to
walk, nausea and vomiting, as well as diaphoresis; and this type
of pain is usually not relieved by flatulence or bowel movements.
The presence of fever, persistent tachycardia, hypotension, or
jaundice in clinical findings, requires a search for complications of
cholelithiasis, including cholecystitis, cholangitis, pancreatitis, or
other systemic causes [10,11].
In physical examination, the signs may appear as the jaundice
and right upper quadrant (RUQ) tenderness during abdominal
palpation. A positive Murphy’s sign may also be elicited. In
emergency cases, the Charcot triad (fever, RUQ tenderness, and
jaundice) can be found, and it strongly indicates the presence
of cholangitis, in which emergency treatment must be promptly
done to prevent the further complications .
Several laboratory tests should be considered in diagnosing
cholelithiasis. A complete blood cell count (CBC) may show an
elevated white blood cell count (WBC), although a normal WBC
result sometimes does not necessarily exclude the possibility in
establishing the diagnosis. Other laboratory components include
the liver function test, lipase, amylase, urinalysis, pregnancy test
in women of childbearing age, and stool guaiac test to rule out of
intestinal bleeding, in case where the symptoms of the occult or
massive gastrointestinal bleeding are present [13,14].
It is essential to have an accurate imaging modality
in cholelithiasis to ensure early intervention and prevent
complications (bacterial infection of the gallbladder, perforation,
etc.). Imaging modality also can prevent unnecessary treatment in
the event of false-positive findings. Some useful diagnostic tools
are ultrasonography (USG), computed tomography (CT), magnetic
resonance cholangiopancreatography (MRCP) .
Ultrasound is the method of choice and also known as the
gold standard for diagnosing cholelithiasis. It is considered an
excellent method because it has a precise diagnostic accuracy and
may be performed to examine nearly all organs of the abdomen,
regardless of its noninvasiveness, lacking of ionizing radiation,
and relatively low cost. A study from Scruggs et al. found that
the USG also has a high sensitivity (97%) and specificity (93.6%)
[15,16]. The previous study reported that one of the most
important advantages of USG over other imaging techniques
in the investigation of cholelithiasis is the ability to assess for
a sonographic Murphy’s sign, which is a reliable indicator of
cholelithiasis with sensitivity of 92%. A wall thickening of the
gallbladder in the presence of gallstones by USG has a positive
predictive value of 95% for the diagnosis of cholelithiasis.
Increased wall thickness of more than 3.5 mm is found to be a
reliable finding of cholelithiasis . Pericholecystic fluid (fluid
around the gallbladder), distended gallbladder, edematous
gallbladder, and gall rocks also can be significantly generated
on USG. Color circulation Doppler USG may show hyperemic,
pericholecystic blood flow, and acute inflammation. Visualization
of USG findings usually shows mobile echogenic foci casting
posterior acoustic shadows (Figure 1), and sometimes a wall
echo-shadow indication is observed if the gallbladder is full of
gallstones. This finding indicates cholelithiasis with cholecystitis
consist of gallbladder distension (> 40 mm) .
Although cholescintigraphy also has both high sensitivity
and specificity (96% and 90%, respectively) for the diagnosis of
cholelithiasis, this modality has several drawbacks that limit its
use in clinical practice. This method is unable to assess structures
outside of the biliary tract, and often lacks in readily available
equipment and personnel, full of radiation exposure, and takes
long hours to perform. It differs from USG that can be performed
immediately and can confidently attribute localized pain to biliary
pathology . For undefined cases, CT or MRCP is considered
as second-line modality that should be performed. Endoscopic
retrograde cholangiopancreatography (ERCP), endoscopic
ultrasonography, percutaneous transhepatic cholangiography
are also recommended. The clinician needs to know about the
stepwise when undefined cases are found (Figure 2).
Treatment of colicky pain primarily involves pain control with
nonsteroidal anti-inflammatory drugs (NSAIDs) or narcotic pain
relievers, and also may be accompanied by symptomatic treatment
for nausea, vomiting, and fever as needed. Another option for pain
control is the anti-spasmodic agent (hyoscine-N-butyl bromide),
which is used to relax and relieve the spasms of the gallbladder.
However, comparison studies have shown that NSAIDs provide
faster and work more effectively as a pain reliever. The patient
should fast as part of the conservative management of colicky
pain and to avoid the release of endogenous cholecystokinin [20-
22]. A study from the European Association for the Study of the
Liver (EASL) showed that the ursodeoxycholic acid (UDCA) is not
indicated as a preventive medication for gallstone disease in the
general population . Otherwise, prophylactic UDCA (500 g/d)
may prevent stone formation for those patients with post-bariatric
surgery . A randomized controlled trial (RCT) study published
in 2003 found a significantly reduced risk of gallstones formation
within 24 months after restrictive gastric bypass surgery (8% vs.
A study by Kotb (2012) reported that UDCA might also reduce
gallstones by the dissolution process in cholelithiasis patients
that had confirmed by USG. Ursodeoxycholic acid has been shown
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
to 3 times daily. The recurrence rate in patients who are treated
with gallstone dissolution agents is 50% within five years .
There are some side effects, including immune suppression,
diarrhea, liver failure, portal hypertension, thrombocytopenia,
and pruritus. Thus, the patients who are using UDCA should be
monitored appropriately .
Surgical management for patients with symptomatic
gallstones can be divided into two categories; (1) those who
have simple biliary colic and (2) those with complications.
Most patients with symptomatic gallstones can be treated
using laparoscopic cholecystectomy. But Cochrane review of
laparoscopic cholecystectomy versus open cholecystectomy
showed the similar results in complication rates and surgical time,
but a shorter hospital stays (three fewer days; 95% CI, 2.3 to 3.9
days) and shorter convalescence period (22 fewer days; 95% CI 8
to 37 days) . Many factors that increase the risk of conversion
to open cholecystectomy include male sex, age 60 years or
older, previous upper abdominal surgery, thickened gallbladder
wall on ultrasonography, and acute cholecystitis . Table 1
provides the indications and contraindications for laparoscopic
Antibiotics pre-operation is not indicated in low-risk patients
undergoing elective surgery, but it may reduce the incidence of
wound infection after laparoscopic cholecystectomy in highrisk
patients such as geriatric patient, comorbidities (diabetes
mellitus, jaundice, cholangitis) [29,30]. The European Association
for the Study of the Liver recommends to limit the use of antibiotic
prophylaxis to a single preoperative dose of intravenous cefazolin
as much as 1 gram, given within one hour of skin excision .
In conclusion, cholelithiasis refers to the formation of
gallstones and may present with or without any obvious
symptoms. Because cholelithiasis is a multifactorial disease,
prompt and structured diagnostic approaches, including history
taking, physical examination, laboratory tests, and imaging tests,
should be performed to decide the management properly and
minimize false-positive events.