Gallstones

Biliary pain

Gallstones cause symptoms when the cystic duct is occluded during the attempted expulsion of bile from the gallbladder. The resulting contraction of the gallbladder smooth muscle results in activation of visceral nerve fibres in the gallbladder wall and the sensation of referred pain in the associated dermatome (T9) in the epigastrium and radiation round or through to the back. Viscerally innervated pain is often poorly localised and may be accompanied by nausea or vomiting. Local cytokine release can cause irritation of the adjacent parietal peritoneum resulting in pain in the right upper quadrant (RUQ). The pain lasts for a significant period of time (typically 30 minutes to several hours) and may be related in part to ischaemia within the gallbladder wall as a result of muscular occlusion of the gallbladder microcirculation. The severity of the pain is sufficient to interfere with performance of daily activities. It is frequently very severe and often described by women as ‘worse than childbirth’. The popular term ‘biliary colic’ is a misnomer since the pain is constant and unrelenting and not colicky in nature. It is therefore more accurately referred to as biliary pain. Similarly, use of the term ‘chronic cholecystitis’ should be avoided since it implies the presence of a chronic inflammatory infiltrate that may or may not be present. The number of stones, their size and the thickness of the gallbladder wall do not correlate well with the presence or absence, or severity of biliary symptoms. In many patients with significant biliary pain, the gallbladder looks quite normal at the time of surgery.

The importance of clarifying what constitutes true biliary pain is to better predict relief following surgery ( Table 12.1 ). Cholecystectomy fails to relieve ‘biliary pain’ in 10–30% of patients with documented gallstones. ^, It is observed that patients who have had cholecystectomy for biliary pain often have improvement in other symptoms, such as belching and low-grade epigastric discomfort (‘biliary dyspepsia’). Some patients may be offered surgery for these symptoms alone. However, these vague symptoms are probably vagal nerve-mediated and also frequently associated with other functional gut disorders such as irritable bowel syndrome or gastro-oesophageal reflux disease. Thus, results for cholecystectomy in patients with ‘biliary dyspepsia’ alone have worse outcomes than in patients who have more classic bouts of acute biliary pain, and should only be undertaken after appropriate exclusion of other causes where possible and with clear counselling that benefits are less likely.

Once patients have started to develop symptoms from their gallstones, the likelihood of having further episodes is approximately 38–50% per annum ^, ; however, approximately 30% of patients will never have further symptoms. The risk of developing complications of gallstones is higher in patients with symptomatic gallstones than in asymptomatic patients and is approximately 1–2% per annum.

Acute cholecystitis

When biliary pain persists for more than a few hours and is accompanied by localised RUQ discomfort, it is termed acute cholecystitis. Pathophysiologically, prolonged obstruction of the cystic duct causes release of prostaglandins within the gallbladder mucosa resulting in fluid secretion producing a cycle of increased distension and further mucosal damage and inflammation. The inflammatory process results in irritation of the parietal peritoneum. Palpation of the RUQ is tender, and inspiration with the examiner’s hand in this region results in pain as the inflamed gallbladder pushes against it (Murphy’s sign), which can similarly be confirmed with the ultrasound probe. Inflammatory markers (WCC/ESR/CRP) may be elevated. Liver function tests (LFTs) are often deranged as a result of localised inflammation within the adjacent liver parenchyma or due to compression of the common bile duct (CBD) from the inflamed gallbladder. Secondary infection can develop in this setting but is rarely the primary event.

The condition may evolve and can result in a variety of complications ( Fig. 12.6 ):

• Obstruction of the cystic duct, usually by a large stone in Hartmann’s pouch, can cause a tense tender gallbladder due to mucus (mucocoele).

• If the obstructed gallbladder becomes infected, it may fill with pus (empyema), presenting classically with high swinging fevers, rising white cell count and a significantly elevated C-reactive protein (> 50).

• Emphysematous cholecystitis may develop when secondary infection in the gallbladder wall occurs with gas-forming bacteria, such as Clostridium welchii , E. coli or anaerobic streptococci. Imaging may reveal the presence of gas within the gallbladder wall. It is most commonly seen in elderly men with diabetes.

• The inflamed gallbladder may become adherent to an adjacent loop of bowel (duodenum, jejunum or colon) and eventually rupture into it, discharging its contents. Rarely a large stone passes through the gallbladder wall into the small bowel and causes obstruction (gallstone ileus) ( Fig. 12.7 ). Gastric outlet obstruction due to impaction of a gallstone in the duodenum is known as Bouveret’s syndrome. Discharge into the colon only rarely causes obstruction due to the larger diameter of the colon but can be encountered at cholecystectomy as a cholecysto-colic fistula.

  

• The gallbladder may rupture into the peritoneal cavity resulting in free pus and generalised peritonitis (1%), or may become walled off by adjacent bowel and omentum and form a localised pericholecystic abscess.

Common bile duct stones

Approximately 8–16% of patients with symptomatic gallbladder stones will have simultaneous CBD stones. With the exception of brown pigment stones, the vast majority (if not all) of these stones originate from the gallbladder and pass from there through the cystic duct into the CBD. The natural history of these CBD stones is unknown, but there is evidence that many do not cause symptoms. Faecal sampling of patients with multiple gallbladder stones confirms that stones often pass freely into the gut without symptoms. Furthermore, studies of patients with known CBD stones awaiting or having had cholecystectomy and who are then re-imaged often show passage of the stones from the CBD. ^, Incidental (asymptomatic) CBD stones are also identified in patients undergoing imaging for unrelated non-biliary conditions. Thus, it would appear that many CBD stones may never cause any problems at all. However, because of the uncertainty in their natural history, once CBD stones are discovered, most clinicians would advise patients to have them removed, even if they are asymptomatic.

When stones enter the CBD and cause partial or complete obstruction, patients present with obstructive jaundice with an elevated bilirubin (conjugated), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT). The transaminases (AST/ALT) may also be elevated (‘a mixed pattern’) as a result of secondary inflammation of the hepatocytes. Classically, obstructive jaundice is accompanied by pale stools due to lack of the brown pigment stercobilin (which requires the presence of bilirubin in the gut) and dark urine (due to increased bilirubin in the urine). These clinical features are not always present, particularly in the early phases of obstruction or with incomplete biliary obstruction. Obstructive jaundice resulting from CBD stones is often associated with biliary pain. This contrasts with jaundice associated with malignant obstruction which is usually painless, but the distinction is not absolute. As obstruction progresses, dilatation of the biliary tract occurs which is evident on ultrasound or cross-sectional imaging (e.g. magnetic resonance imaging [MRI], computed tomography [CT]).

CBD stones, when present, are only occasionally identified with ultrasound because the lower part of the bile duct lies behind the gas-filled duodenum preventing visualisation. The presence of a dilated CBD or intrahepatic ducts with deranged LFTs raises the suspicion of CBD stones, which are best visualised by magnetic resonance cholangiopancreatography (MRCP) or endoscopic ultrasound (EUS). A recent meta-analysis has shown that EUS and MRCP are equally good at identifying CBD stones, with similar sensitivity and specificity. However, EUS is more costly, less widely available and more invasive than MRCP. These techniques have replaced the use of endoscopic retrograde cholangiopancreatography (ERCP) (with its attendant risks) as a diagnostic tool.

If infection develops in an obstructed bile duct, jaundice is invariably accompanied by high temperatures and RUQ pain (Charcot’s triad) and is termed cholangitis. Fevers are typically fluctuating, with high temperatures of 39–40°C punctuated by chills and shaking bouts (rigors). Cholangitis is caused by secondary infection within the biliary tract, usually caused by enteric bacteria from the duodenum (most commonly Gram-negative spp.— E. coli [25–50%], Klebsiella spp. [15–20%], Enterobacter spp. [5–10%] or less commonly, Gram-positive bacteria, Enterococcus spp. [10–20%]). Early management with intravenous antibiotics (broad-spectrum cephalosporin or ciprofloxacin) followed by early biliary decompression by stone removal or stenting is essential. Failure to treat this condition frequently results in septicaemia, which can be fatal.

Acute pancreatitis

CBD stones (usually small) may pass out of the papilla at the lower end of the bile duct and in some cases result in acute pancreatitis. The most popular theory for the pathogenesis of gallstone pancreatitis is that an impacted gallstone in the distal bile duct obstructs the pancreatic duct, increasing pancreatic pressure, thereby damaging ductal and acinar cells (see Chapter 15 ).

Mirizzi syndrome

First described by Argentinian surgeon Pablo Mirizzi in 1948, the term is used to describe the situation where a stone impacted in Hartmann’s pouch produces an inflammatory process that results in adherence of Hartmann’s pouch to the CBD with loss of the space between the two structures (i.e. obliteration of Calot’s triangle). The result is a partial obstruction of the common hepatic duct (CHD) with deranged LFTs. The most useful subclassification is into type I, where there is no fistula present, and type II, where the stone has eroded into the bile duct itself resulting in a cholecysto-choledochal fistula ( Fig. 12.8 ).

Intrahepatic stone disease

In certain parts of the world, primary bile duct stones (synonyms include intrahepatic stone disease [IHSD], oriental hepatolithiasis, cholangiohepatitis, recurrent pyogenic cholangitis, Hong Kong disease) form by a very different pathogenesis to cholesterol and black pigment stones, and present with a different clinical picture. The highest prevalence of this disease is seen in South-East Asia where it has been associated with the liver fluke Clonorchis sinensis . However, it also exists in other areas of the world, most notably South Africa, Pakistan and Colombia in the absence of Clonorchis , where the main linked epidemiological factor is severe poverty. In these communities, there may be an association with the round worm Ascaris lumbricoides infestation.

Stones formed in this disease are very different from cholesterol- and bilirubin-rich stones and are brown, soft and friable. The stones form in any part of the biliary tract as a result of anaerobic bacteria secreting enzymes that hydrolyse ester and amide linkages in biliary lipids as insoluble anions or calcium salts. These precipitates deposit on obstructing elements such as small cholesterol crystals, black stones from the gallbladder, parasite eggs and dead worms or flukes.

Patients with IHSD present with sepsis and RUQ pain, and initial management is with antibiotics. Symptoms are far more commonly related to ductal stones, and infective and inflammatory processes around the stones result in strictures and proximal dilatation of the ducts. Simple cases caught early can be managed by decompression of pus from the CBD with a plastic stent. Subsequent definitive surgical management aims to clear the biliary tract of stones, provide adequate biliary drainage and, where necessary, provide adequate access to the biliary duct. When there is an extrahepatic or hilar duct stricture, hepaticojejunostomy (HJ) is performed leaving the afferent loop long and fixing it to the abdominal wall as an ‘access loop’ which permits subsequent percutaneous or endoscopic management of recurrent stones and strictures. A proportion of patients require resection of an atrophied portion of the liver containing multiple stones. The disease more frequently affects the left lobe than the right. Patients with IHSD have a 10% risk of developing cholangiocarcinoma.

Conservative

Patients with gallstones without symptoms do not require treatment. The risk of people with asymptomatic cholelithiasis developing symptoms (biliary pain) is low, averaging 2–3% per year, or approximately 10% by 5 years. Major complications related to gallstones are very rare in asymptomatic patients. Expectant management is therefore an appropriate choice for silent gallstones in the general population.

Non-operative management

Even in the laboratory, gallstones are difficult to dissolve and most chemicals that successfully dissolve gallstones are too toxic to ingest or inject into the gallbladder (e.g. methyl tetra butyl ether [MTBE], monooctanoin, carbon tetrachloride). During the 1970–80s, there were many attempts to develop strategies to achieve non-medical management of gallstones by oral dissolution, injection of solvents into the biliary tract and extracorporeal shock wave lithotripsy (ESWL). However, none achieved significant reliable dissolution of the stones, even in highly selected study groups, and all required long-term bile salt therapy (with a high incidence of abdominal cramps and diarrhoea) to prevent recurrent stone formation. With the development of laparoscopic cholecystectomy (LC) in the late 1980s with its low morbidity and ability to definitively remove the ‘stone factory’, research in this area has dwindled.

Alternative treatments such as the ‘gallbladder flush’ (essentially consisting of giving purgative agents such as Epsom salts, olive oil and lemon juice) have been popularised by the Internet, but there is no evidence of any efficacy, although they do result in the production of small pellet-like faeces which can be mistaken by enthusiasts of the procedures as stones!