Table 61-3 Natural History of Gallstones

An additional therapy, although not commonly employed, is extracorporeal shock wave lithotripsy

(ESWL). This therapy uses energy (“shock”) waves, produced by different methods depending on the

generator technology, to dissolve stones. ESWL can dissolve small calculi or decrease the size of larger

calculi and make them potentially extractable by endoscopic or percutaneous techniques, if in the CBD

or distal cystic duct, or dissolvable by oral therapy if present in the gallbladder. It is a relatively safe

procedure with rare complications, including: hematoma (biliary or otherwise), bowel perforation, and

necrotizing pancreatitis.24

Symptomatic Patients

It is estimated that 2% to 3% per year of those with known gallstones will develop symptoms

11 and 1%

to 2% will develop more complex problems (such as cholecystitis, pancreatitis, or cholangitis) annually

(Table 61-3).12 Those who develop symptoms will most often have biliary colic, or right upper quadrant

(RUQ) pain, which will often recur. Biliary colic will often last for several hours after onset before

subsiding. Biliary colic develops secondary to intermittent impaction of gallstones at the gallbladder

neck as the gallbladder contracts in order to deliver its contents into the CBD. In more than 50% of

patients it occurs following a fatty meal. Biliary colic can be associated with belching, bloating, and

even nausea or emesis. Over time this intermittent obstruction leads to increased tension in the

gallbladder wall and more chronic pain and inflammation known as chronic cholecystitis.

COMPLICATED GALLSTONE-RELATED DISEASE

Complicated gallstone-related disease (acute cholecystitis [AC], choledocholithiasis, and associated

consequences of gallstone pancreatitis or cholangitis) will occur in 0.3% to 3% of patients per year.25

These complications increase the morbidity and potential mortality of patients with gallstones.

Acute Cholecystitis

AC develops when a gallstone(s) lodges in the gallbladder neck (infundibulum) obstructing bile flow

into the CBD. This obstruction leads to biliary stasis, gallbladder wall edema, venous obstruction, and in

extreme cases, eventual arterial obstruction causing necrosis of the gallbladder wall. Its course can

range from mild pain with fevers to frank sepsis secondary to perforation or development of

emphysematous/gangrenous cholecystitis. Clinically, patients present in a similar manner to those with

biliary colic; however the pain is constant, unrelenting, and often associated with fevers, tachycardia,

and a leukocytosis. The diagnosis is typically made with a thorough history and physical examination, in

which the patient may present with midepigastric or RUQ pain, as well as, localized peritoneal

irritation. Murphy’s sign, which is defined by cessation of inspiration secondary to pain, due to the

presence of an inflamed gallbladder during deep abdominal palpation at the midclavicular line of the

RUQ, is pathognomonic for AC.

Imaging and Diagnosis

A variety of imaging tests can be used when evaluating the patient with AC, each of which have

different strengths and weaknesses, and serve as an adjunct to a thorough history and physical

examination.

Ultrasound (US) uses oscillating sound waves to measure differences in tissue densities and interfaces

between liquids and solids and is the backbone of imaging for gallstone disease (Fig. 61-4). The primary

advantages of US are that it is readily available, quickly performed, and avoids ionizing radiation. The

main disadvantage is that it is user-dependent, and technique and experience are therefore quite

important.26 AC can be diagnosed by various US criteria, with the higher number of criteria met on US

examination, the more likely for cholecystitis to be present. These criteria include gallbladder wall

thickening >5 mm, pericholecystic fluid, gallstones, and a positive sonographic Murphy sign

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characterized by pain and cessation of inspiration when the probe is pressed over the gallbladder. A

2012 meta-analysis by Kiewiet et al.27 which included 26 studies with 2,847 patients, evaluated the role

of US as a tool to diagnose AC, and reported a sensitivity of 81% and specificity of 83% with the

comparison being against surgical pathologic findings in the majority of patients.

HIDA scan (biliary scintigraphy) first came into use in the late 1970s.28 The injectable radioactive dye

(derivatives of technetium and iminodiacetic acid) used is preferentially taken up by the liver and

excreted into the bile and should fill both the CBD and gallbladder if there is free flow through the

entire biliary system. A HIDA scan is considered positive for AC if there is lack of visualization of the

gallbladder due to cystic duct occlusion from gallstones which does not allow the radioactive tracer to

enter the gallbladder (Fig. 61-5). The overall sensitivity for AC of a HIDA scan is 95% to 98% with a

specificity of >90%.27,28 A false-positive HIDA scan can occur in various situations, including

consumption of a recent meal (the gallbladder is contracted due to CCK), prolonged fasting (the

gallbladder has concentrated thick bile which acts as a mechanical obstruction to entrance of the tracer),

chronic cholecystitis, or the presence of underlying hepatobiliary disease.

Limitations of HIDA scans are that it is not always readily available, especially after hours, and

require exposure to ionizing radiation; thus, most clinicians will begin with US and then use HIDA to

clarify equivocal US results. Several studies have looked at the utility of adding HIDA to US in the case

of diagnostic dilemma, but the combined modalities do not appear to add sensitivity or specificity for

detection of AC, although they may provide additional morphologic information.29–31

CT scans are typically less helpful for diagnosing uncomplicated gallstone disease, as most gallstones

(85%) are not radiopaque. CT scans are limited in their ability of evaluating the CBD and identifying an

obstruction of the cystic duct, which is a prerequisite for the diagnosis of AC.26,32–34 They have been

shown to be less sensitive and specific than US.32 CT scans can be helpful, however, in evaluating

patients for complications of AC (Fig. 61-4). Gangrenous cholecystitis, which is the most common AC

complication, occurs in up to 38% of patients with AC. Gallbladder perforation and abscess formation

can be seen in up to 8% to 12% of AC cases. A CT scan can detect a defect in the gallbladder wall in

53% of patients with early perforation whereas US cannot easily delineate a mural defect, unless large,

although both will likely help detect the resulting abscess formation (Fig. 61-6).

Figure 61-4. Classic acute cholecystitis seen on US (A) with luminal distention, gallbladder wall thickening >5 mm, and

pericholecystic fluid; CT scan (B) demonstrates similar findings of wall thickening and pericholecystic stranding; MRI T2 fatsaturated sequence (C) demonstrates gallbladder wall edema and pericholecystic fluid, as well as small stones in the gallbladder

neck. (Image courtesy of Aarti Sekhar, MD and David Schuster, MD, Emory University Department of Radiology.)

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MRI has only been evaluated in small studies in the setting of AC. Its sensitivity and specificity are

similar to that of US (approximately 80% to 85% for both). MRI is useful for evaluation of the biliary

tree and to assess for the presence of choledocholithiasis; however, it can overestimate the presence of

gallbladder wall inflammation (Fig. 61-4). Advancements in MRI protocols employing unique tracers

that are taken up and excreted in the biliary tree similar to iminodiacetic acid compounds, such as

Eovist, are currently under investigation.35 Ultimately, the current cost and availability of MRI

machines make it of limited use for the diagnosis of AC.

Treatment

The treatment of AC can consist of medical or surgical therapies and the correct treatment modality will

depend on the individual clinical scenario. The medical treatment of AC involves nothing per os,

parenteral hydration, and antibiotics until the patient’s clinical examination improves and pain resolves.

The diet is then slowly advanced and the patient is kept on a low-fat diet until cholecystectomy is

performed. Despite symptom resolution, the patient should undergo an interval cholecystectomy, as the

likelihood of a second biliary-related complication is high. Surgical therapy consists of either a

laparoscopic or open cholecystectomy, or placement of a cholecystostomy tube in combination with

medical therapy.

5 Cholecystectomy. Cholecystectomy is considered standard therapy for patients with symptomatic

gallstones and AC. With regard to the surgical treatment of AC, the discussion in the literature has been

the timing of the cholecystectomy – early versus delayed. Early cholecystectomy removes the

pathologic source, usually within the first 72 hours of presentation. Certain clinicians advocate for

delayed cholecystectomy to allow the acute inflammatory response to resolve potentially making the

surgery safer with fewer complications and morbidity, such as bile duct injuries, bleeding, and

conversion from laparoscopic to open procedure.

Figure 61-5. HIDA scan (A) demonstrating positive result with uptake of tracer within liver and excretion through the common

bile duct with filling of the duodenum, but absence of filling of gallbladder (arrowhead) even on delayed postmorphine imaging

(B), confirming cystic duct occlusion. Final panel (C), shows normal filling of gallbladder (arrow), or a negative result. (Image

courtesy of Aarti Sekhar, MD and David Schuster, MD, Emory University Department of Radiology.)

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Figure 61-6. Examples from two patients with focal perforations of the gallbladder wall seen on US (A) and CT scan (B). Large

perforations are visible with either modality, but CT is more sensitive for detecting smaller perforations. (Image courtesy of Aarti

Sekhar, MD and David Schuster, MD, Emory University Department of Radiology.)

6 A 2006 meta-analysis showed no significant differences in patient outcomes between early and

delayed surgeries with respect to bile duct injuries, bleeding complications, laparoscopic-to-open

conversion, postoperative infection, and patient death.36 It was noted that over 23% of delayed patients

presented with complications requiring emergent cholecystectomy. Furthermore, total hospital stay,

including the index admission and subsequent admissions for biliary complications and later

cholecystectomy, was significantly shorter for early cholecystectomy, leading to a decreased cost to the

patient and system.

Early has also been somewhat of a misnomer, as traditionally this early approach has consisted of

performing a cholecystectomy within 72 hours of the onset of symptoms. A Cochrane review in 2006,37

which included 6 randomized trials with 488 patients, compared early (within 7 days of presentation) to

late (>6 weeks after initial treatment) cholecystectomy and found similar results to the above metaanalysis with no increase in terms of complications and outcomes. Multiple studies demonstrate that

early should be within the index admission and the 72-hour limit is not as much a steadfast rule given

improved skills of surgeons with laparoscopic surgery and the understanding that surgery delayed to a

different admission could potentially lead to worse complications.

A recent study from Italy seems to confirm these data. Patients (n = 316) were enrolled in a

prospective study38 to assess the benefit of immediate cholecystectomy during the index admission or

delayed surgery after at least 4 weeks. As with the other studies, the complication profiles were no

different between the two groups; however, the subgroup analysis within the early intervention group

showed that immediate surgery on admission or early surgery within 48 hours was associated with

shorter operative time, similar conversion and complication rates, and shorter hospital stay. Within the

delayed group, 26% required rehospitalization and 37% required urgent reevaluation prior to planned

surgery.

Percutaneous Cholecystostomy. In the otherwise healthy patient with AC, laparoscopic

cholecystectomy should be considered the therapy of choice during the index hospitalization. However,

in the elderly patient with poor performance status, multiple comorbidities, or for the extremely ill

patient in the intensive care unit, the underlying medical status may impact increased perioperative risk

and therefore preclude surgical intervention. Percutaneous cholecystostomy (PC) may be employed as a

bridge or final therapy in such patients. This procedure was first described in the 1980s by Radder et

al.39 and involves the placement of a percutaneous transhepatic drain into the gallbladder (Fig. 61-7).

The transhepatic approach has remained the method of choice to reduce intraperitoneal bile leak in case

of tube dislodgement. Use of this approach has grown over 500% since 1994, along with the field of

interventional radiology.40 Typically, rapid patient improvement is seen following decompression in

combination with antibiotics tailored to bacterial isolates. In most patients, an interval cholecystectomy

will be performed 6 weeks or more after the drain is placed. Removing the drain alone is usually not

sufficient, as the cystic duct obstruction is typically still present. If Bile is draining from the catheter,

then it may be possible to remove the catheter after 6 weeks without removing the gallbladder in

patients with questionable fitness for surgery.

Acalculous Cholecystitis

Acute acalculous cholecystitis (AAC) represents 12% of all cases of AC with the incidence being

significantly higher in intensive care unit patients.41 AAC is associated with increased bile stasis and

therefore decreased gallbladder emptying, which typically occurs in the setting of severe illness with

multiple contributing mediators, such as the inflammatory response, total parenteral nutrition, and highdose narcotics. The diagnosis of ACC requires a high index of clinical suspicion, as patients are often

critically ill and unable to communicate symptoms. The potential consequences of late diagnosis are

considerable, with gallbladder ischemia and progression to gangrene and eventual perforation resulting

in a mortality rate of up to 30%.42 Diagnosis may be made using bedside ultrasonography following

similar criteria as used for acute calculous cholecystitis, with the exception of lack of calculi. The

sensitivity of US in this setting ranges from 50% to 100% with a specificity of 90% to 94%. HIDA scan

with morphine amplification can be used to increase bile secretory pressure and allow bile to reflux

through a contracted gallbladder neck, thereby decreasing false-positive rates, providing sensitivity

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