Therapy of gallstone disease: What it was, what it is, what it will be

Table 1 Non-genetic risk factors for gallbladder stones

Age

Female gender

High-calorie, low-fiber diet

High-carbohydrate diet, dietary glycemic load

Obesity

Physical inactivity

Rapid weight loss/surgery for obesity

Total gastrectomy with lymph node dissection

Spinal cord injury

Infections: enterohepatic Helicobacter species, malaria

Biliary strictures

Drugs: estrogens, calcineurin inhibitors, fibrates, octreotide, ceftriaxone

Total parenteral nutrition

Duodenal diverticulum

Extended ileal resection (black pigment stones)

Vitamin B12/folic acid deficient diet (black pigment stones)

Pancreatic insufficiency

Cholangitis (brown pigment bile duct stones)

Adapted from Portincasa et al^[1] and Grünhage et al^[160] with permission.

Table 2 Major features of the uncomplicated biliary colic

Pathogenesis	Visceral pain caused by the impaction of the stone in the cystic duct or the ampulla of Vater, followed by distension of the gallbladder and/or biliary tract with activation of visceral sensory neurons[161]
Onset	Not exclusively postprandial, typically intermittent
Intensity	Mean visual analogue scale of 9 cm on a 0-10 cm scale
Localization	Most frequently right upper quadrant of the abdomen and/or the epigastrium (representative dermatomes T8/9)
Duration	Generally longer than 15-30 min. Can last several hours and be associated non-specific symptoms of indigestion
Radiation	Angle of the right scapula and/or shoulder (about 60% of cases), retrosternal area (less than 10% of cases)
Associated features	Urgency to walk[162] (two-third of patients), nausea or vomit[42,161,162]
Relief	If the stone returns into the gallbladder lumen, passes through the ampulla of Vater into the duodenum or migrates back to the common bile duct[26]
First-line therapy	Fast-acting narcotic analgesics (meperidine[163]) or non-steroidal anti-inflammatory drugs (NSAIDs) (im or iv ketorolac or ibuprofen po) which could also reduce the risk of evolution towards acute cholecystitis[164-167]
Second-line therapy	Antispasmodic (anticholinergic) agents like hyoscine (scopolamine). Less effective than NSAIDs[164]
Recommendations	Fasting, to avoid release of endogenous cholecystokinin and further gallbladder contraction

Adapted from[25,63,148] with permission.

Table 3 Indications for “prophylactic” cholecystectomy (i.e., asymptomatic gallstone patients bearing a high risk of becoming symptomatic)

Children (because they are exposed to the long-term physical presence of stones[58])

Morbid obese patients undergoing bariatric surgery (high risk to become symptomatic during rapid weight loss[62])

Increased risk for gallbladder cancer[63]

Patients with large gallstones (greater than 3 cm)[64,65]

A “porcelain” gallbladder[66] or gallbladder polyps rapidly growing or larger than 1 cm

Native Americans with gallstones (risk of gallbladder cancer 3 to 5 percent)[67]

Gallstone patients with sickle cell anemia (formation of calcium bilirubinate gallstones due to chronic hemolysis. Patients may become symptomatic with recurrent episodes of abdominal pain[68])

Coexistence of small gallstones and gallbladder dysmotility (increased risk of pancreatitis[47])

Adapted from[25,63,148] with permission.

Table 4 Major features of the complicated biliary colic

Additional findings compared to uncomplicated biliary pain	Leukocytosis, nausea, jaundice, vomiting, fever
Underlying potential complications	Acute pancreatitis, acute cholecystitis, biliary obstruction and cholangitis, gallbladder perforation, abscess formation, mucocele of the gallbladder
Decision	Quick admission to the hospital
Therapies	Antibiotics or invasive procedures with or without surgical procedures (Figure 1)
	Early laparoscopic cholecystectomy recommended between 2 and 4[168] in mild and moderate acute cholecystitis

Adapted from[25,63,148] with permission.