Introduction

Gallstones and related disorders account for all but a small proportion of biliary tract disease in most countries. Gallstone disease is also known as cholelithiasis and choledocholithiasis is when stones are present in the bile ducts.

Most gallstone-related disease presents with pain, typically located in the epigastrium or right hypochondrium (right upper quadrant or RUQ). The character of the pain varies but in most cases, it is acute and intermittent. Less commonly, gallstone disease presents as pain and jaundice caused by a stone passing into and obstructing the common bile duct.

Gallstone composition

In developed countries, most gallstones are of mixed composition and contain a predominance of cholesterol; this is mixed with some bile pigment (calcium bilirubinate) and other calcium salts. A small proportion is virtually ‘pure’ cholesterol stones (‘cholesterol solitaire’). In Asia, most gallstones are composed of bile pigment alone. The composition and pathogenesis of the various types of gallstone are summarised in Table 20.1 (and see Fig. 20.2), and some examples are illustrated in Figure 20.3.

The physical structure of mixed gallstones gives an insight into their sequence of formation. There is usually a small core of organic material, often containing bacteria. The main body of the stone is made up of concentric layers, demonstrating that stones form in a series of discrete precipitation events. Furthermore, in the same gall bladder, there are often several ‘families’ of gallstones, each of a different size. This suggests each generation began at a different time, presumably due to some transient change in local conditions. All families then build up at the same rate by lamination, leading to the range of different sizes. Radioisotope dating studies have shown that the average gallstone is 11 years old when removed!

The main factors in stone formation are: (a) changes in concentration of the different constituents of bile, (b) biliary stasis and (c) infection. It is likely that several subtle abnormalities combine synergistically to bring about precipitation of bile constituents.

Bile salts and lecithin are responsible for maintaining cholesterol in a stable micelle formation. The normal micellar structure of bile supports a greater concentration of cholesterol than could otherwise be held in solution and is therefore inherently unstable. An excess of cholesterol in proportion to bile salts and lecithin is probably one of the main factors in cholesterol stone formation. This is supported by the fact that patients in whom the terminal ileum has been resected or who have chronic distal ileal disease have a three-fold risk of developing cholesterol-rich stones. The mechanism is likely to be as follows: the terminal ileum is the main site for reabsorption of bile salts and when it is diseased or has been removed, reabsorption declines, leading to bile salt loss via the bowel and, eventually, a decline in the bile salt pool. The remaining bile salts are then insufficient to maintain the micellar structure of cholesterol in suspension.

Precipitation from bile is enhanced by biliary stasis. This occurs if the gall bladder becomes obstructed or contractility becomes defective. It is not known whether obstruction of the gall bladder outlet is a primary event in formation of stones but it probably plays a part in their continued accretion. Obstruction can be caused by dysfunction of the spiral valve in the cystic duct, by reflux of duodenal contents (which may be infected) or by small stones already formed. The muscular gall bladder wall is damaged by longstanding inflammation or infection which interferes with its ability to empty. Pregnancy is also a predisposing factor.

The role of inflammation and infection

Inflammation and infection probably both play a part in gallstone formation. Abnormalities of bile composition may cause chemical inflammation of the gall bladder, resulting in inflammatory exudation and accumulation of inflammatory debris. Bacteria usually form the organic nidus upon which gallstones are built; they enter the gall bladder intermittently by reflux from the duodenum or via the bloodstream. This process is probably normal but becomes pathological if the bacteria are not flushed out, as occurs when the gall bladder does not adequately empty. In support of this is the fact that faecal organisms can be cultured from at least 25% of cholecystectomy specimens.

The role of chronic obstruction

Most gall bladders removed for chronic pain show histological features more in keeping with a chronic obstructive aetiology than an infective one. These include atrophic mucosa, submucosal and subserosal fibrosis, hypertrophy of the muscular wall, and mucosal diverticula extending into the muscular layer (known as Rokitansky–Aschoff sinuses). Evidence of active or previous infection is uncommon. In some cases the gall bladder is so grossly scarred, distorted or contracted that its absorptive and contractile functions have been completely destroyed.

Other pathological mechanisms

In about 10% of patients with typical symptoms of gall bladder disease, no stone can be found during investigation or at operation. In some of these, a stone may have passed out of the duct system into the bowel. In others, acute or chronic inflammation occurs independently of stones, called ‘acalculous cholecystitis’; once again, chronic obstruction may be the cause. Finally, the terms ‘biliary dyskinesia’ and ‘cystic duct syndrome’ may sometimes explain the condition where patients have typical symptoms of gall bladder disease but standard investigations are essentially normal. When biliary manometry is used, some patients have an abnormally high pressure in the sphincter of Oddi. Confirming this diagnosis is difficult but a fair proportion of patients suspected of this are cured by endoscopic sphincterotomy.

Epidemiology of gallstones

In developed countries, at least 10% of adults probably develop gallstones during their lifetime, although most remain asymptomatic. Gallstones are rare before adulthood and increase in prevalence with age. Women are affected four times more often and pregnancy appears to be an important predisposing factor; obesity and diabetes may also play a part. The typical patient is said to be a ‘fair fat fertile female of forty’, but many gallstone patients do not fit this description. Gallstone disease is rare in rural communities of developing countries but is increasing with urbanisation. Western-style processed foods, high in fats and refined carbohydrates but poor in fibre, may be responsible. Dietary contributions to gall bladder disease support the theory that changes in composition of bile are important in stone pathogenesis.

The non-jaundiced patient

Patients with gallstones but no history of obstructive jaundice do not require preoperative investigation for duct stones apart from an ultrasound scan and LFTs. If cholecystectomy is needed, intraoperative (or perioperative) cholangiography may be carried out. A cannula is passed through the cystic duct into the common bile duct and radiopaque contrast material injected to fill the biliary tree. X-rays or fluoroscopic imaging are then used to demonstrate the duct morphology and abnormalities such as duct dilatation, filling defects caused by stone, or distortion of the tapering lower end of the common duct, as well as obstruction of flow into the duodenum. If cholangiography shows stones, the duct may be explored at the time or else dealt with later by endoscopic retrograde cholangio-pancreatography (ERCP).

Patients with a history of transient jaundice possibly attributable to stones will have either operative cholangiography at cholecystectomy or preoperative ERCP.

The jaundiced patient

When obstructive jaundice has been diagnosed, it is important to distinguish between stone and tumour in order to plan appropriate management. Ultrasonography is usually the initial investigation. This shows the extent of dilatation of intrahepatic and extrahepatic ducts and may even show a stone lodged at the lower end of the duct. If stones are in the gall bladder, this suggests stones are blocking the duct rather than tumour, but the two can coexist. The ultrasound scan will usually demonstrate the presence of a carcinoma of the pancreatic head or enlarged lymph nodes in the porta hepatis; either may cause extrahepatic biliary obstruction.

Ultrasound may make the diagnosis, but if more information is required, biliary tract morphology can be outlined using magnetic resonance cholangio-pancreatography (MRCP) which produces images of the biliary tree and pancreatic ducts (see Ch 5, p. 65; Fig. 5.6). If MRCP does not yield the necessary information, the ducts can be visualised by direct introduction of contrast. There are two methods: ERCP and, more rarely, percutaneous transhepatic cholangiography. ERCP is the more useful investigation; it also allows the ampullary region to be inspected for tumour. If stones are found in the common bile duct, it is often possible to perform immediate endoscopic sphincterotomy to release the stones, thus diagnosing and relieving the jaundice in one procedure. This may be life-saving for the patient with ascending cholangitis and is the treatment of choice on its own for the patient who is a poor risk for laparotomy or laparoscopy.

Percutaneous transhepatic cholangiography (Ch 5, p. 65; Fig. 5.6) is used in exceptional circumstances, for example if ERCP is unsuccessful because of previous gastric surgery. It involves inserting a long, fine (22 gauge) needle through the skin into one of the dilated intrahepatic ducts under radiological control. Contrast medium is then injected. An obstructing stone produces a characteristic rounded filling defect, contrasting with the tapering stricture typical of tumour.

Endoscopic ultrasound scanning (EUS), i.e. scanning via the endoscope, is a useful technique to show greater detail at the lower end of the common bile duct or to examine lesions in the ampulla or head of the pancreas with greater clarity.

Clinical features

The most common reason for symptoms from gallstones is probably intermittent cystic duct obstruction by stone. The pain is severe; it typically rises to a plateau over a few minutes then continues unrelentingly. Note that this pain does not have the strikingly intermittent brief peaks of other forms of colic (e.g. ureteric). These patients may be in agony until the pain resolves spontaneously after several hours or after opiate analgesia. Vomiting is often associated with the attack and the patient feels exhausted and sore for the next day or so. There is commonly a history of previous similar episodes. There are few positive findings on examination: the patient is afebrile but there may be some local tenderness due to gall bladder distension. If the attack does not settle within 24 hours, acute cholecystitis is a more likely diagnosis (see below).

Management

Most cases of biliary colic can safely be managed at home if the diagnosis is recognised. Relief of pain usually requires only one injection of an opiate and the attack passes. Severe attacks of biliary colic usually prompt emergency hospital admission since the differential diagnosis includes other conditions that may require urgent operation, e.g. perforated peptic ulcer. Ultrasound examination should be performed early since early diagnosis may save several unnecessary days in hospital. In acute gallstone disease, cholecystectomy scheduled for the next available list is preferred by many surgeons and is generally safe, but others perform the operation electively at a later date. Early operation appears to be the better option, reducing the risk of the complications of gallstones.

If a mucocoele of the gall bladder is found on ultrasonography, the attack is likely to persist and there is a high risk of an empyema of the gall bladder developing. In this case, cholecystectomy often becomes obligatory during the current admission.

Cholecystectomy is the definitive treatment for attacks of biliary colic. Patients are frequently put on a low-fat diet initially or whilst awaiting operation and this often relieves symptoms, presumably by removing a stimulus to gall bladder contraction. In younger patients, cholecystectomy is typically straightforward. The gall bladder is usually found to contain stones or thick dark biliary sludge and its wall is often thin, although it may sometimes be inflamed. In some patients, the gall bladder is thickened and scarred and technically more difficult to remove. Techniques of cholecystectomy are discussed on pages 290 onwards.

Pathophysiology and clinical features

Several factors contribute to causing acute inflammation in an obstructed gall bladder. These include physical and chemical irritation and, later in the episode, bacterial infection. The clinical result is acute cholecystitis, which often presents as a surgical emergency. In contrast to biliary colic, the patient is usually systemically unwell with a fever and tachycardia. On examination there is tenderness in the right upper quadrant, more marked on inspiration and a tender inflammatory gall bladder mass may be palpable. The term ‘Murphy’s sign’ is often misused in this context; it was originally used to describe tenderness at the tip of the ninth rib. Being inflammatory in origin, the clinical course of acute cholecystitis is more prolonged than biliary colic, usually lasting several days before settling or else precipitating urgent surgery.

Management

Ultrasonography is usually sufficient to support the diagnosis by revealing stones and a thickened gall bladder wall. Oral intake should be restricted to fluids, and an intravenous infusion set up if necessary. Most patients with acute cholecystitis have only a chemical inflammation and therefore do not need antibiotics. When acute cholecystitis is accompanied by gall bladder infection, symptoms and signs are more marked and antibiotics should then be given.

Acute cholecystectomy

The patient with acute cholecystitis will need a cholecystectomy at some stage. Early cholecystectomy, performed within a few days of the onset of the attack, is becoming more popular. The procedure is as safe as elective surgery, convenient for the patient and an efficient usage of hospital beds. The alternative policy of conservative management involves discharging the patient after the acute attack resolves, with readmission for elective cholecystectomy after about 6 weeks, by which time the inflammation has usually settled. However, in the mean time there is a risk of further acute attacks or another manifestation of gallstone disease such as acute pancreatitis. Even if delayed cholecystectomy is preferred, the acute attack may not settle, necessitating cholecystectomy on the same admission.

When operation is performed during the acute illness, the gall bladder is found to be obstructed and tense and may be grossly inflamed, thickened and scarred. The serosal surface is oedematous and inflamed with petechial haemorrhages or even purulent exudate and there are fibrinous adhesions to nearby structures. The gall bladder neck or cystic duct is blocked by an impacted stone and the gall bladder is usually found to contain further stones or sludge mixed with inflammatory exudate. Great care must be taken to avoid damaging the bile ducts. Bowel organisms can be cultured from the contents in about 70% of cases. A bacterial culture swab should be taken from within the gall bladder at operation as any postoperative infective complications are likely to involve the same organisms.

Pathophysiology

Bile duct stones nearly always originate in the gall bladder and pass through the cystic duct. Most stones are small enough to pass out of the biliary system into the duodenum but may cause biliary colic or mild jaundice during transit.

Initially, stones in the bile ducts are small but if they stay in the bile duct without passing, they may enlarge progressively in situ. This is evident from the occasional finding of multiple faceted gallstones fitting neatly together in the common duct and which could only have formed within the duct. The common bile duct is narrowest at its lower end and stones too large to pass out tend to lodge there. Such a stone becomes impacted, causing progressive jaundice, or acts as a ball-valve, causing intermittent jaundice. Obstruction results in gradual dilatation of the biliary tree; longstanding dilatation does not regress even after the obstruction is removed and may lead to stagnation of bile and further stone formation. Note that the gall bladder rarely distends in this condition even when the common bile duct is completely obstructed, because of the inflammatory fibrosis or mural hypertrophy caused by gallstones (Courvoisier’s law—see Ch. 18, p. 259).

Clinical presentations of stones in the biliary tract

• Very slow action

• Only small—less than 1 cm—cholesterol-predominant stones can be dissolved

• High rate of stone recurrence after successful treatment—up to 50% after 2 years

• Frequent drug-related side-effects, e.g. severe diarrhoea and hepatic damage

Indications for surgery and preparation of the patient

There are two main indications for cholecystectomy:

In most cases high-quality biliary ultrasound is the only imaging study required. This demonstrates gall bladder disease and gallstones and the diameter of the intrahepatic and extrahepatic bile ducts. Information from ultrasound about gall bladder wall thickness or the number and size of stones has not proved useful in predicting the feasibility of laparoscopic surgery. If there are stones in the duct system, common duct exploration is added to cholecystectomy or else stones are extracted at ERCP.

Any jaundiced patient is at particular risk during surgery because of infection, hepatic impairment, defective clotting, acute renal failure and venous thrombosis (see Table 18.2, p. 262). It is often preferable to relieve obstructive jaundice before surgery by endoscopic sphincterotomy and stone extraction or bile duct stenting to minimise some of these complications. In patients presenting with jaundice caused by operable carcinoma of the pancreas, however, the obstruction is often intentionally not relieved preoperatively because duct dilatation simplifies its anastomosis to bowel. It also minimises the risk of introducing infection into a stagnant biliary tree.

Cholecystectomy—open versus laparoscopic surgery

Laparoscopic cholecystectomy is now the gold standard treatment for gallstones. All surgeons performing this operation must also be able to competently perform the laparoscopic operation but also a potentially difficult open operation to cope with the occasional conversion to open operation brought about by unexpected difficulties or complications arising during a laparoscopic operation.

Operations on the common bile duct

Complications of biliary surgery

The procedure-specific complications of laparoscopic cholecystectomy are listed in Table 20.2. General complications of cholecystectomy are described below.