The liver and biliary tract

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14 The liver and biliary tract

O.J. Garden

Chapter contents

The liver

The gallbladder and bile ducts

The liver

Anatomy

The liver is the largest abdominal organ, weighing approximately 1500 g. It extends from the fifth intercostal space to the right costal margin. It is triangular in shape, its apex reaching the left midclavicular line in the fifth intercostal space. In the recumbent position, the liver is impalpable under cover of the ribs. The liver is attached to the undersurface of the diaphragm by suspensory ligaments that enclose a ‘bare area’, the only part of its surface without a peritoneal covering. Its inferior or visceral surface lies on the right kidney, duodenum, colon and stomach.

Topographically, the liver is divided by the attachment of the falciform ligament into right and left lobes; fissures on its visceral surface demarcate two further lobes, the quadrate and caudate (Fig. 14.1A). However, it is the liver segmental anatomy, as defined by the distribution of its blood supply, that is important to the surgeon.

Fig. 14.1 Anatomy of the liver.

A The broken line represents the separation between right and left hemilivers. B Segmental anatomy and venous drainage.

Segmental anatomy

The portal vein and hepatic artery divide into right and left branches in the porta hepatis. Occluding either branch at surgery produces an easily visible line of demarcation that runs from the gallbladder bed behind and to the left of the inferior vena cava, thus separating the two hemilivers. Each hemiliver is further divided into four segments corresponding to the main branches of the hepatic artery and portal vein. In the left hemiliver, segment I corresponds to the caudate lobe, segments II and III to the left lobe (or left lateral section), and segment IV to the quadrate lobe. The remaining segments (V–VIII) comprise the right hemiliver (Fig. 14.1B).

Blood supply and function

The liver normally receives 1500 ml of blood per minute and has a dual blood supply, 75% coming from the portal vein and 25% from the hepatic artery, which supplies 50% of the oxygen requirements. The principal venous drainage of the liver is by the right, middle and left hepatic veins, which enter the vena cava (Fig. 14.1B). In 25% of individuals, there is an inferior right hepatic vein, and numerous small veins drain direct into the vena cava from the caudate lobe (segment I). The functional unit of the liver is the hepatic acinus. Sheets of liver cells (hepatocytes) one cell thick are separated by interlacing sinusoids through which blood flows from the peripheral portal tract into the hepatic acinus to the central branch of the hepatic venous system. Bile is secreted by the liver cells and passes in the opposite direction along the small canaliculi into interlobular bile ducts located in the portal tracts (Fig. 14.2).

Fig. 14.2 The hepatic lobule.

Sinusoids drain into the central hepatic vein.

The liver has an important role in nutrient metabolism and is responsible for storing glucose in the form of glycogen, or converting it to lactate for release into the systemic circulation. Amino acids are utilized for hepatic and plasma protein synthesis or catabolized to urea. The liver has a central role in the metabolism of lipids, bilirubin and bile salts, drugs and alcohol. It is the principal organ for storage of a number of minerals and vitamins, and is responsible for the production of the coagulation factors I, V, XI, the vitamin K-dependent factors II, VII, IX and X as well as proteins C and S and antithrombin. The liver is also the largest reticuloendothelial organ in the body and its Kupffer cells play a role in the removal of damaged red blood cells, bacteria, viruses and endotoxin, much of which enter the body from the gut.

Summary Box 14.1 Surgical anatomy

• The liver is divisible into right and left hemilivers (each having four segments) using a line running from the gallbladder fossa to the inferior vena cava

• Each hemiliver receives a branch of the hepatic artery and portal vein; 75% of liver blood flow and 50% of its oxygen supply are provided by the portal vein

• The hepatocytes are arranged in lobules, each of which has a central branch of the hepatic vein and peripheral portal tracts (containing a branch of the hepatic artery, portal vein and bile duct)

• Liver anatomy allows the surgeon to perform right hepatectomy, left hepatectomy and extended right hepatectomy (i.e. resecting all of the liver to the right of the falciform ligament). Resection of individual segments is also possible.

Jaundice is caused by an increase in the level of circulating bilirubin and becomes obvious in the skin and sclera when levels exceed 50 μmol/l (Fig. 14.3). It may result from excessive destruction of red cells (haemolytic jaundice), from failure to remove bilirubin from the blood stream (hepatocellular jaundice), or from obstruction to the flow of bile from the liver (cholestatic jaundice) (Fig. 14.4). Congenital non-haemolytic hyperbilirubinaemia (Gilbert’s syndrome) is a relatively rare cause of jaundice due to defective bilirubin transport; the jaundice is usually mild and transient, and the prognosis is excellent.

Fig. 14.3 Patient demonstrating the features of jaundiced skin and sclera.

Fig. 14.4 Types of jaundice.

To the surgeon, the most important type of haemolytic jaundice is that caused by hereditary spherocytosis, in which splenectomy may be necessary (Ch. 15). Haemolytic jaundice may also occur after blood transfusion and after operative or accidental trauma, when haematoma formation produces a pigment load that exceeds hepatic excretory capacity.

Hepatocellular jaundice is usually a medical rather than a surgical condition, although its recognition in patients presenting with abdominal pain is important, as surgical intervention may aggravate the hepatocellular injury.

Cholestatic jaundice due to intrahepatic obstruction of bile canaliculi may be a feature of acute and chronic liver disease and can be caused by drugs (e.g. chlorpromazine). This form of jaundice must be differentiated from that due to extra-hepatic obstruction, the cause of which has most surgical relevance. Extrahepatic obstruction most commonly results from gallstones or cancer of the head of the pancreas. Other causes include cancer of the periampullary region or major bile ducts, extrinsic compression of the bile ducts by metastatic tumour, iatrogenic biliary stricture and choledochal cyst.

Diagnosis

History and clinical examination

An accurate, rapid diagnosis of the cause of jaundice allows prompt institution of appropriate treatment (Fig. 14.5). The age, sex, occupation, social habits, drug and alcohol intake, history of injections or infusions, and general demeanour of the patient must be considered. A history of intermittent pain, fluctuant jaundice and dyspepsia suggests calculous obstruction of the common bile duct, whereas a history of weight loss and relentless progressive jaundice favours a diagnosis of neoplasia. Obstructive jaundice is likely if there is a history of passage of dark urine and pale stools, and if the patient complains of pruritus (owing to an inability to secrete bile salts into the obstructed biliary system). Hepatocellular jaundice is likely if there are stigmata of chronic liver disease, such as liver palms, spider naevi, testicular atrophy and gynaecomastia. The abdomen must be examined for evidence of hepatomegaly or gallbladder distension, and for signs of portal hypertension such as splenomegaly, ascites and large collateral veins (caput medusae) in the abdominal wall.

Fig. 14.5 Investigation of the jaundiced patient.

Congenital abnormalities

Up to 5% of the population has simple liver cysts. They are lined by biliary epithelium and contain serous fluid, but never communicate with the biliary tree. They rarely produce symptoms, are associated with normal liver function, and on ultrasound or CT have no discernible wall (Fig. 14.6). In the few patients who develop symptoms, cysts tend to recur following aspiration, and sclerosis by alcohol injection is of little value for large symptomatic cysts. Surgical management consists of deroofing and may be undertaken by laparoscopic means. Polycystic disease is a rare cause of liver enlargement and may be associated with polycystic kidneys as an autosomal dominant trait. In symptomatic patients, it may be necessary to combine a deroofing procedure with hepatic resection or to consider liver transplantation.

Fig. 14.6 CT demonstrating multiple biliary cysts appearing as hypodense areas within both lobes of the liver (arrowed).

Summary Box 14.2 Jaundice

• Jaundice is a yellowish discoloration of the tissues that becomes clinically apparent when serum bilirubin levels exceed 50 μmol/l (normal < 20 μmol/l)

• It may be due to excessive haemolysis, hepatic insufficiency or cholestasis; cholestatic (obstructive) jaundice is the type encountered in surgical practice

• The two most common causes of surgical obstructive jaundice are cancer of the head of the pancreas and stones in the common bile duct (choledocholithiasis)

• In cholestatic jaundice, the bilirubin has been conjugated by the hepatocytes and is therefore soluble in water and can be excreted in the urine; patients with obstructive jaundice typically have dark urine and pale stools and may have pruritus (thought to be due to the accumulation of bile salts)

• Obstructive jaundice is characterized by elevated serum alkaline phosphatase levels in addition to hyperbilirubinaemia, and may be accompanied by modest elevations in transaminase (aminotransferase) levels, reflecting liver damage.

Cavernous haemangiomas are one of the most common benign tumours of the liver (up to 5% of population) and may be congenital. Women are affected six times more frequently than men. Most haemangiomas are small solitary subcapsular growths found incidentally at laparotomy or autopsy, but they are sometimes detected on ultrasound examination as densely hyperechoic lesions that mimic hepatic tumours. These lesions rarely give rise to pain. Resection may be considered for symptomatic lesions exceeding 5 cm in diameter.

Liver trauma

After the spleen, the liver is the solid organ most commonly damaged in abdominal trauma, particularly following road traffic accidents. Stab injuries and gunshot wounds of the liver are also increasing in incidence. These are considered in Chapter 7.

Hepatic infections and infestations

Liver abscesses can be classified as bacterial, parasitic or fungal. Bacterial abscess is the most common type in Western medicine, but parasitic infestation is an important cause world-wide. Fungal abscesses are found in patients receiving long-term broad-spectrum antibiotic treatment or immunosuppressive therapy, and may complicate actinomycosis.

Pyogenic liver abscess

Infection from the biliary system is now more common due to the increasing use of radiological and endoscopic intervention. Infection may spread through the portal vein from abdominal sepsis (e.g. appendicitis, diverticulitis), via the hepatic artery from a septic focus anywhere in the body, or by direct spread from a contiguous organ (e.g. empyema of the gallbladder). Abscess formation may follow blunt or penetrating injury, and in one-third of patients the source of infection is indeterminate (cryptogenic). Common organisms are:

• Streptococcus milleri

• Escherichia coli

• Streptococcus faecalis

• Staphylococcus aureus

• anaerobes (Bacteroides spp).

Clinical features

The onset of symptoms is often insidious and the patient may present with pyrexia of unknown origin. There is sometimes a history of sepsis elsewhere, particularly within the abdomen, and pain in the right hypochondrium. Other patients present with swinging pyrexia, rigors, marked toxicity and jaundice. The liver is often enlarged and tender.

Investigations

Plain radiographs may show elevation of the diaphragm, pleural effusion and basal lobe collapse. Leucocytosis is usually present and liver function tests are deranged. Ultrasonography or CT is used to define the abscess (which is often irregular and thick-walled) and to facilitate percutaneous aspiration for culture. ERCP may be useful if biliary obstruction is thought to be responsible.

Management

Untreated abscesses often prove fatal because of spread within the liver to multiple sites, and because of septicaemia and debility. The principles of treatment are percutaneous drainage of accessible abscesses under ultrasound or CT guidance, and antibiotic therapy selected on the basis of culture of blood or pus. It is exceptional to resort to surgical drainage. Percutaneously or surgically placed drainage tubes are left in place and the size of the cavity is monitored by CT or serial X-rays following the injection of contrast material. Multiple small abscesses may require prolonged treatment with antibiotics for up to 8 weeks. Investigation is required to detect the source (e.g. colonoscopy, ERCP for stone removal).

Amoebic liver abscess

Entamoeba histolytica is a protozoal parasite that infests the large intestine and is endemic in many tropical regions. Trophozoites released by the cyst in the intestine may penetrate the mucosa to gain access to the portal venous system and so spread to the liver. The abscess is large and thin-walled, is usually solitary and in the right lobe, and contains brown sterile pus resembling anchovy sauce.

Clinical features

Right upper quadrant pain may be accompanied by anorexia, nausea, weight loss and night sweats. Tender enlargement of the liver is invariable, although jaundice is uncommon. Other signs include basal pulmonary collapse, pleural effusion and leucocytosis.

Investigations

Ultrasonography and CT are used to demonstrate the site and size of the abscess, which often has poorly defined margins. The stools should be examined for amoebae or cysts. Direct and indirect serological tests to detect amoebic protein are available.

Management

Early diagnosis is important, and treatment may be commenced empirically in areas where the problem is endemic. Treatment consists of the administration of metronidazole (800 mg 8-hourly for 5 days) and usually results in rapid resolution. The abscess should be aspirated by needle puncture, if there is no clinical response within 72 hours. If untreated, an amoebic abscess may rupture into the peritoneal cavity or into a bronchus.

Hydatid disease

This less common infestation is caused in humans by one of two forms of tapeworm, Echinococcus granulosus and E. multilocularis. The adult tapeworm lives in the intestine of the dog, from which ova are passed in the stool; sheep or goats serve as the intermediate host by ingesting the ova whereas humans are accidental hosts (Fig. 14.7). The condition is most common in sheep- and goat-rearing areas. Ingested ova hatch in the duodenum and the embryos pass to the liver through the portal venous system. The wall of the resulting hydatid cyst is surrounded by an adventitial layer of fibrous tissue and consists of a laminated membrane lined by germinal epithelium, on which brood capsules containing scolices develop.

Fig. 14.7 Life cycle of Echinococcus granulosus.

Clinical features

The disease may be symptomless, but chronic right upper quadrant pain with enlargement of the liver is the common presentation. The cyst may rupture into the biliary tree or peritoneal cavity, the latter sometimes causing an acute anaphylactic reaction due to absorption of foreign hydatid protein. Other complications include secondary infection and biliary obstruction with jaundice.

Investigations

Eosinophilia is common and serological tests, such as complement fixation, are available to detect the foreign protein. Hydatid cysts commonly calcify and may be seen on a plain film of the abdomen. Alternatively, they can be detected by ultrasound or CT of the liver and are recognizable by their thick wall, which may contain multiple daughter cysts.

Management

In asymptomatic patients, small calcified cysts may require no treatment. Patients can be treated successfully with albendazole or mebendazole but this may be prolonged. Large symptomatic cysts are best managed by complete excision, together with the parasites contained within. A laparoscopic approach is possible for simple accessible cysts.

Portal hypertension

Portal hypertension is caused by increased resistance to portal venous blood flow, the obstruction being prehepatic, hepatic or posthepatic (Table 14.1). Rarely, it results primarily from an increase in portal blood flow. The normal pressure of 5–15 cmH₂O in the portal vein is consistently exceeded (above 25 cmH₂O). Portal vein thrombosis is a rare cause and is most commonly due to neonatal umbilical sepsis. The most common cause of portal hypertension is cirrhosis resulting from chronic liver disease and is characterized by liver cell damage, fibrosis and nodular regeneration. The fibrosis obstructs portal venous return and portal hypertension develops. Arteriovenous shunts within the liver also contribute to the hypertension.

Table 14.1 Causes of portal hypertension

Obstruction to portal flow:

Prehepatic

Intrahepatic

• Cirrhosis

• Schistosomiasis

Posthepatic

• Budd–Chiari syndrome

• Constrictive pericarditis

Increased blood flow (rare)

• Arteriovenous fistula

• Increased splenic blood flow in hypersplenism

Alcohol is the most common aetiological factor in developed countries, whereas in North Africa, the Middle East and China, schistosomiasis due to Schistosoma mansonii is a common cause. Chronic active hepatitis and primary and secondary biliary cirrhosis may result in portal hypertension, but in a large number of patients the cause remains obscure (cryptogenic cirrhosis).

Post-hepatic portal hypertension is rare. It is most frequently due to spontaneous thrombosis of the hepatic veins and this has been associated with neoplasia, oral contraceptive agents, polycythaemia and the presence of abnormal coagulants in the blood. The resulting Budd-Chiari syndrome is characterized by portal hypertension, caudate hypertrophy, liver failure and gross ascites.

Effects of portal hypertension

As a result of gradual chronic occlusion of the portal venous system, collateral pathways develop between the portal and systemic venous circulations. Portosystemic shunting occurs at three principal sites (Fig. 14.8). The most important is the development of varices in the submucosal plexus of veins in the lower oesophagus and gastric fundus. Oesophageal varices may rupture, to cause acute massive gastrointestinal bleeding in about 40% of patients with cirrhosis. The initial episode of variceal haemorrhage is fatal in about one-third of patients, and recurrent haemorrhage is common. Bleeding from retroperitoneal and periumbilical collaterals (‘caput medusae’) is troublesome during abdominal surgery, and collaterals may develop and cause bleeding at the site of stomas. Anorectal varices are not uncommonly found at proctoscopy but rarely cause bleeding.

Fig. 14.8 The portal venous system.

Sites of portosystemic shunting are marked 1–3. Retroperitoneal communications also exist.

Progressive enlargement of the spleen occurs as a result of vascular engorgement and associated hypertrophy. Haematological consequences are anaemia, thrombocytopenia and leucopenia (with the resulting syndrome of hypersplenism). Ascites may develop and is due to increased formation of hepatic and splanchnic lymph, hypoalbuminaemia, and retention of salt and water. Increased aldosterone and antidiuretic hormone levels may contribute. Portosystemic encephalopathy is due to an increased level of toxins such as ammonia in the systemic circulation. This is particularly likely to develop where there are large spontaneous or surgically created portosystemic shunts. Gastrointestinal haemorrhage increases the absorption of nitrogenous products and may precipitate encephalopathy.

Clinical features

Patients with cirrhosis frequently develop anorexia, generalized malaise and weight loss. Clinical manifestations include hepatosplenomegaly, ascites, jaundice and spider naevi. Slurring of speech, a flapping tremor or dysarthria may point to encephalopathy, and this may be precipitated or intensified by the accumulation of blood in the gastrointestinal tract. The serum bilirubin may be elevated and the serum albumin depressed. Anaemia may be present and the leucocyte count raised (or depressed if there is hypersplenism). The prothrombin time and other indices of clotting may be abnormal. Clinical and biochemical parameters are used as the basis of the modified Child’s classification (Table 14.2). Patients allocated to grade A have a good prognosis, whereas those in grade C have the worst prognosis.

Table 14.2 Assessment of patients with portal hypertension using a modification of Child’s grading system

Patients with portal hypertension may be referred to a surgeon because of active uncontrolled bleeding from oesophageal varices, or for consideration of elective surgery for varices that have been resistant to non-surgical management.

Acute variceal bleeding

Patients presenting with acute upper gastrointestinal bleeding are examined for evidence of chronic liver disease (EBM 14.1). The key investigation during an episode of active bleeding is endoscopy. This allows the detection of varices and defines whether they are or have been the site of bleeding. It is important to remember that peptic ulcer and gastritis are common complaints that occur in 20% of patients with varices.

14.1 Variceal bleeding in cirrhosis: assessment and prophylaxis

‘Severity of cirrhosis is best described using the Child-Pugh score. If grade 3 varices are diagnosed, patients should have primary prophylaxis, irrespective of the severity of the liver disease. Pharmacological therapy with propranolol is the best available modality for primary prophylaxis, with variceal band ligation recommended in cases of intolerance or contraindication to propranolol.’

Jalan R, Hayes PC, British Society of Gastroenterology. Gut 2000; 46 suppl 3–4:III 1–III 15.

Management

The priorities in the management of bleeding oesophageal varices are summarized in Table 14.3.

Table 14.3 Priorities in the management of bleeding oesophageal varices

Active resuscitation

• Group and cross-match blood

• Establish i.v. infusion line(s)

Central venous pressure

Assessment of coagulation status

• Prothrombin time

• Platelet count

Urgent endoscopy Control of bleeding

• Endoscopic banding or injection sclerotherapy

• Tamponade (Minnesota tube) if bleeding uncontrolled

• Pharmacological measures (e.g. vasopressin/octreotide)

Treatment of hepatocellular decompensation Treatment/prevention of portosystemic encephalopathy Prevention of further bleeding from varices

• Endoscopic banding or injection sclerotherapy

• Stapled oesophagogastric junction

• Portosystemic shunting/transjugular intrahepatic portosystemic stent shunting (TIPSS)

• Liver transplantation

Active resuscitation

The aim is to replace blood loss quickly with a view to urgent endoscopy. Many patients have coagulation defects from the outset, and thrombocytopenia is a common manifestation of hypersplenism. Fresh blood is preferred for transfusion purposes and the advice of the haematologist is sought regarding the use of fresh-frozen plasma (FFP) or platelet transfusion.

Endoscopy and control of bleeding

Endoscopy will reveal tortuous varices in three columns most prominent in the lower third of the oesophagus. Haemorrhage usually occurs from varices at the lowest few centimetres of the oesophagus. Rarely, bleeding occurs from varices in the gastric fundus. Although the synthetic form of somatostatin, octreotide, can be used to lower portal venous pressure and arrest bleeding, the injection of a sclerosant such as ethanolamine, or the application of bands is now used to arrest the bleeding at endoscopy (EBM 14.2). If haemorrhage is torrential and prevents direct injection, balloon tamponade may be used to stop the bleeding. The four-lumen Minnesota tube (Fig. 14.9) has largely replaced the three-lumen Sengstaken–Blakemore tube. The four lumina allow:

• aspiration of gastric contents

• compression of the oesophagogastric varices by the inflated gastric balloon

• compression of the oesophageal varices by the inflated oesophageal balloon

• aspiration of the oesophagus and pharynx to reduce pneumonic aspiration.

14.2 Control of variceal bleeding

‘Variceal band ligation is the method of choice for control of variceal haemorrhage, with endoscopic variceal sclerotherapy as second choice. If endoscopy is unavailable, vasoconstrictors such as octreotide or glypressin, or a modified Sengstaken tube may be used while more definitive therapy is arranged. In case of bleeding that is difficult to control, a modified Sengstaken tube should be inserted until further endoscopic treatment, transjugular intrahepatic portosystemic stent shunting (TIPSS) or surgical treatment, with the mode of treatment (surgical intervention such as oesophageal transection or TIPSS) determined by the specialist centre.’

Jalan R, Hayes PC, British Society of Gastroenterology. Gut 2000; 46 suppl 3–4:III 1–III 15.

Fig. 14.9 Oesophageal tamponade using a Minnesota tube.

Balloon tamponade arrests bleeding from varices in over 90% of patients, but the tube is not left in place for more than 24–36 hours for fear of causing oesophageal necrosis. Tamponade should be regarded as a holding measure that allows further resuscitation and treatment of hepatic decompensation before more definitive measures are used.

Prevention of further bleeding

A number of methods are now available to reduce the risk of further variceal bleeding (EBM 14.3). Injection sclerotherapy is repeated at weekly or fortnightly intervals until the varices are completely sclerosed but excessive intervention may cause ulceration and necrosis. Endoscopic banding is favoured since there is a reduced risk of complication. Surgical disconnection (stapled oesophageal transection) is used rarely. The gastric vein and short gastric veins are ligated, and the distal oesophagus is transected and reanastomosed just above the cardia using a stapling gun (Fig. 14.10) to occlude flow into the varices. It carries considerable morbidity and mortality when employed as a last resort in the emergency situation.

14.3 Prevention of further variceal bleeding and infection

‘Following control of active variceal bleeding, the varices should be eradicated using variceal band ligation. TIPSS may be used in certain centres with particular expertise; it is more effective than endoscopic treatment in reducing variceal rebleeding but does not improve survival and is associated with more encephalopathy.’

‘Infection is common after upper gastrointestinal bleeding in cirrhotic patients and is a major cause of morbidity and mortality All patients presenting with an episode of variceal bleed should have antibiotic prophylaxis with ciprofloxacin 1 g/day for 7 days.’

Jalan R, Hayes PC, British Society of Gastroenterology. Gut 2000; 46 suppl 3–4:III 1–III 15.

Fig. 14.10 Oesophageal stapling.

The gun is inserted through an anterior gastrostomy. A ligature is tied just above the cardia, invaginating a flange of oesophageal wall between the two parts of the gun. Inset: the gun has been fired, simultaneously resecting a full-thickness ring of oesophageal wall and anastomosing the cut ends with staples.

Emergency portosystemic shunting

Shunt surgery carries a high mortality and has been abandoned in most centres. Elective portosystemic shunting is still used occasionally to decompress the portal system and reduce the risk of further variceal haemorrhage in patients with preserved liver function, but portosystemic encephalopathy can be troublesome. In severe liver disease, transplantation is more likely to be considered if there is no contraindication.

Types of shunt procedure

Most portosystemic shunts have been replaced by non-surgical approaches to treatment. In transjugular intrahepatic portosystemic stent shunting (TIPSS, Fig. 14.11), a metal stent is inserted via the transjugular route using a guidewire passed through the hepatic vein to the intrahepatic branches of the portal vein. The technique is a relatively safe means of decompressing the portal system as general anaesthesia and laparotomy are avoided. The risk of encephalopathy is similar to that of a surgical portosystemic shunt, but the procedure is now considered routinely before surgical intervention in both the acute and elective setting.

Fig. 14.11 Transjugular intrahepatic portosystemic stent shunting (TIPSS).

Summary Box 14.3 Portal hypertension

• Portal hypertension is almost always due to obstruction to portal flow (rather than increased inflow), and may be prehepatic, hepatic or posthepatic

• Cirrhosis of the liver is the most common cause of portal hypertension in developed countries, and alcoholic cirrhosis is most often responsible

• Portosystemic shunts develop between gastric and oesophageal veins, in the retroperitoneum and periumbilical area, and occasionally in the anorectum. Varices in the submucosa of the lower oesophagus are a common source of major bleeding, but gastritis (portal gastropathy) can be responsible

• Child’s grading (A, B or C) is based on encephalopathy, ascites, prothrombin time, bilirubin and albumin levels, and is a valuable prognostic index

• Variceal bleeding may be controlled by endoscopic banding or injection sclerotherapy, although balloon tamponade (four-lumen Minnesota tube) may sometimes be needed

• Surgical portosystemic shunts effectively decompress oesophageal varices and reduce rebleeding, but can cause encephalopathy and have been largely replaced by transjugular intrahepatic portosystemic stent shunting (TIPSS)

• Although banding (or injection sclerotherapy) reduces the risk of rebleeding and may improve survival rates, long-term outcome is determined by the nature and severity of the underlying liver disease.

Ascites

Ascites can be controlled by bed rest, salt and water restriction, and the aldosterone inhibitor spironolactone. If refractory, ascites can be treated by inserting a peritoneojugular (LeVeen) shunt, which allows one-way flow between the peritoneum and the jugular vein (Fig. 14.12). It is unusual for the shunt to remain patent for more than 12 months, but this may suffice for patients with refractory ascites and advanced liver disease who are not candidates for liver transplantation.

Fig. 14.12 Peritoneovenous (Le Veen) shunt to relieve ascites.

Tumours of the liver

Hepatic tumours can be benign or malignant, and primary or secondary. Primary tumours may arise from the parenchymal cells, the epithelium of the bile ducts, or the supporting tissues.

Benign hepatic tumours

Cavernous haemangioma

This is the most common benign liver tumour (see above). These lesions rarely reach a sufficient size to produce pain, abdominal swelling or haemorrhage. Heart failure rarely develops, if there is a large arteriovenous communication. Lesions discovered incidentally at laparotomy should be left alone; needle biopsy can be hazardous. Large symptomatic lesions should normally be resected only by an experienced surgeon.

Biliary hamartoma

These are small fibrous lesions that are often situated beneath the capsule of the liver. They can be mistaken for a small metastatic tumour unless a biopsy is obtained.

Focal nodular hyperplasia (FNH)

This is more common in females. The lesion is generally asymptomatic and may regress with time or on withdrawal of the contraceptive pill. Hyperplasia can be differentiated from adenoma by the central fibrous scar, which is often visible on ultrasound or CT (Fig. 14.13). Such lesions do not undergo malignant transformation and do not require excision unless symptomatic.

Fig. 14.13 Intravenous enhanced CT scan demonstrating a hypervascular lesion in the left lobe of the liver (arrowed).

This symptomatic focal nodular hyperplastic lesion was removed by left lobectomy.

Liver cell adenoma

This is relatively uncommon and is found almost exclusively in women. The use of contraceptives containing high levels of oestrogen have been implicated causally. The majority present as solitary, well-encapsulated lesions, but malignant transformation has been reported. They may be asymptomatic but generally present with right hypochondrial pain as a result of haemorrhage within the tumour. Superficial tumours may bleed spontaneously and present with symptoms of haemoperitoneum. Adenomas may be detected by ultrasonography or CT. LFTs and serum α-fetoprotein levels are usually normal.

Treatment consists of formal hepatic resection because of the difficulties of distinguishing adenoma from a well- differentiated hepatoma, concerns that lesions may undergo malignant transformation, and the known risk of spontaneous haemorrhage. There is recent evidence to suggest that cytokeratin 7 and 19 immunostains along with neuronal adhesion molecule taken from liver biopsy can help in differentiating hepatic adenoma from FNH when radiological imaging is inconclusive.

Primary malignant tumours of the liver

Hepatocellular carcinoma (hepatoma)

Hepatocellular carcinoma (HCC) is relatively uncommon in the developed world but is common in Africa and the Far East. HCC is more common in males and it is thought to result in over 600,000 deaths worldwide each year. In the West, about two-thirds of patients have pre-existing cirrhosis and many others have evidence of hepatitis B or C infection. In Africa and the East, ‘aflatoxin’ (derived from the fungus, Aspergillus flavus, which contaminates maize and nuts) is an important hepatocarcinogen.

Clinical features

The diagnosis is usually made late in the course of the disease. In non-cirrhotic patients, the tumour may have grown to a considerable size before giving rise to abdominal pain or swelling. In cirrhotic patients, hepatoma may become manifest as sudden deterioration in liver function, often associated with extension of the tumour into the portal venous system. Common presenting features would involve progression of existing liver disease symptoms, and may include abdominal pain, weight loss, abdominal distension, fever and spontaneous intraperitoneal haemorrhage. Jaundice is uncommon unless there is advanced cirrhosis. Examination may reveal features of established liver disease and hepatomegaly is invariable.

Investigations

LFTs are generally deranged. Although early detection of hepatocellular carcinoma in susceptible individuals can be pursued by a policy of serial measurement of α-fetoprotein (an oncofetal antigen) and ultrasound scanning, this tumour marker is present in only one-third of the white population with hepatocellular carcinoma, compared to 80% of African patients with this disease.

The lesion may be detected and characterized by abnormal ultrasound scanning. Percutaneous needle aspiration cytology and needle biopsy for histological confirmation should be reserved for patients who are not being considered for hepatic resection, as these investigations carry a small but significant risk of tumour dissemination and haemorrhage. There are accepted criteria based on radiology and tumor marker levels that accept a diagnosis of HCC without the need for biopsy (EBM 14.4).

14.4 Diagnosis of HCC established

• if two imaging modalities show a coincidental nodule with arterial hypervascularization regardless of AFP levels

• if a single modality shows a lesion when the AFP is > 400 ng/ml

• histological diagnosis is required if the nodule is less than 2 cm in diameter.

Bruix J, Sherman M, Hepatology 2005; 42: 1208–1236.

Abdominal CT or MRI is valuable in planning resection and excluding the presence of nodal involvement. Hepatocellular carcinoma is seen as an extremely vascular lesion on arteriography, and propagation of tumour thrombus along the portal vein or its branches may be apparent. Pulmonary metastases may not be evident on chest X-ray and their presence should be excluded by a thoracic CT. Peritoneal dissemination may only be excluded by laparoscopy.

Management

In non-cirrhotic patients, large tumours (particularly those of the fibrolamellar type) are likely to be amenable to liver resection. Cirrhotic patients have less hepatic functional reserve, and even those with well-preserved liver function may only tolerate limited segmental resection if there is significant portal hypertension. In cirrhotic patients, multicentricity is common and satellite lesions often surround the primary tumour, so that cure is uncommon.

For advanced tumours, systemic chemotherapy with doxorubicin (adriamycin), methotrexate or 5-fluorouracil may have palliative value, although response rates of less than 20% are the norm. Sorafenib, a multitargeted oral kinase inhibitor, has recently been shown in a phase II trail to prolong survival in patients with HCC. Encouraging results have been reported following local embolization with chemotherapy by selective arteriography (transarterial chemo-embolization – TACE) and percutaneous ablation using radiofrequency and microwave energy have been used to useful effect for small lesions not amenable to surgery. Future efforts may involve a combination of these methods.

The disease is usually advanced at presentation and the 5-year survival rate is less than 10%. Liver transplantation has been used in the treatment of this tumour, but the best results have been reported in cirrhotic patients in whom an incidental hepatoma has been found on examination of the resected specimen following the transplant. If transplantation is not otherwise contraindicated, eligibility criteria have been extended for cirrhotic patients with a single tumour of 5 cm or less in diameter, or with no more than three tumour nodules each one 3cm or less in size (Milan criteria).

Cholangiocarcinoma

This adenocarcinoma may arise anywhere in the biliary tree, including its intrahepatic radicles. It accounts for less than 10% of malignant primary neoplasms of the liver in Western medicine, although its incidence is rising. Risk factors include chronic parasitic infestation of the biliary tree in the Far East, and choledochal cysts (see below).

Jaundice, pain and an enlarged liver are the common presenting features, although there may be co-existing biliary infection causing the tumour to masquerade as a hepatic abscess. Resection offers the only prospect of cure but is seldom feasible when cholangiocarcinoma arises in the liver substance. Cholangiocarcinoma arising from the extrahepatic bile ducts is considered below.

Other primary malignant tumours

• Angiosarcoma (Fig. 14.14). This rare tumour of the liver may arise after industrial exposure to vinyl chloride or exposure to the previously used radiological contrast medium, Thorotrast

• Haemangioendothelioma. This presents as a diffuse multifocal tumour and is rarely resectable at presentation

• Biliary cystadenoma. This rare condition of the liver, with a marked female predominance, has a 1:4 risk of malignant transformation and should be resected.

Fig. 14.14 Angiosarcoma.

A CT demonstrating a lesion in segment V (arrowed). B Angiography shows an extremely vascular lesion (arrowed) taking its blood supply mainly from an aberrant right hepatic artery (RHA) arising from the superior mesenteric artery (SMA).

Metastatic tumours

The liver is a common site for metastatic disease; secondary liver tumours are 20 times more common than primary ones. In 50% of cases, the primary tumour is in the gastrointestinal tract; other common sites are the breast, ovaries, bronchus and kidney. Almost 90% of patients with hepatic metastases have tumour deposits in other sites.

Hepatomegaly and tenderness are distinctive features, and individual deposits may be palpable in advanced disease. The patient may be cachectic, and ascites or jaundice may be present. Pyrexia occurs in up to 10% of patients. The alkaline phosphatase and γ-glutamyl transpeptidase are often raised. Ultrasound and CT may demonstrate multiple filling defects. The diagnosis can be confirmed by aspiration cytology or needle biopsy undertaken under ultrasound control. Such invasive investigation may be unnecessary when resection is being considered.

There is no effective treatment for most patients with hepatic metastases due to the extent of liver involvement and the presence of extrahepatic disease. Nonetheless, for some tumours, notably those arising from the colon and rectum, disease may be confined to the liver and there is strong evidence of survival benefit if these are resected. Assessment of resectability will require a careful search to exclude or assess extrahepatic disease. This may necessitate colonoscopy and CT of chest, abdomen and pelvis. A more radical approach to resection of liver metastases has resulted from advances in chemotherapy and has been combined with staged resection of liver disease and preoperative portal embolization to induce hypertrophy of the intended residual liver. In well-selected patients, 5-year survival rates of 30–40% have been reported following resection. Non-curative resection may be considered exceptionally as a means of palliation in patients with symptomatic hepatic metastases such as a carcinoid or other neuroendocrine tumours.

Liver resection

Resection involves mobilization of the liver from its peritoneal attachments. Following isolation, ligature and division of the appropriate vessels, the devascularized lobe or segment is separated by careful dissection, which may be facilitated by the use of an ultrasonic dissector. Intervening biliary and vascular channels can be defined and divided between ligatures. The hepatic veins or tributaries are controlled by suture ligation following removal of the resected specimen.

Modern techniques of hepatic resection have greatly reduced operative blood loss, with a subsequent reduction in morbidity and mortality. Enhanced recovery programmes after liver surgery are associated with reduced use of abdominal drains, immediate restitution of oral intake and early mobilization in the postoperative period. Postoperative monitoring is undertaken in a high dependency environment and should include early blood gas, glucose and lactate measurement. Hepatic dysfunction may be evident from prolongation of the prothrombin time in major liver resectional surgery but complications such as postoperative haemorrhage and intra-abdominal/wound infection are less common.

Liver transplantation

This is considered in Chapter 25.

The gallbladder and bile ducts

Anatomy of the biliary system

The biliary tree consists of fine intrahepatic biliary radicles that drain individual liver segments before forming the right and left hepatic ducts. The left hepatic duct runs a mainly extrahepatic course and joins the right hepatic duct to form the common hepatic duct. This is joined at a variable position by the cystic duct to form the common bile duct, which ends at the ampulla of Vater, usually in the second part of the duodenum (Fig. 14.15). The common bile duct is approximately 8 cm long and up to 10 mm in diameter. It lies in the free edge of the lesser omentum before passing behind the first part of the duodenum and through the head of the pancreas. It is usually joined by the pancreatic duct just before entering the duodenum.

Fig. 14.15 Anatomy of the biliary tree.

The gallbladder lies in a bed on the undersurface of the liver between its right and left halves. It is a muscular structure with a fundus, body and neck. Hartmann’s pouch is a dilatation of the gallbladder outlet adjacent to the origin of the cystic duct, in which gallstones frequently become impacted. The gallbladder is supplied by the cystic artery, a branch of the right hepatic artery.

Physiology

Bile salts and the enterohepatic circulation

Bile acids are synthesized by the liver from cholesterol. The primary bile acids, chenodeoxycholic and cholic acid, are conjugated with glycine or taurine to increase their solubility in water, and the conjugates (e.g. glycocholic and taurocholic acid) form sodium and potassium bile salts. In the intestine, bacterial action produces the secondary bile salts, deoxycholic and lithocholic acid.

Bile salts can combine with lipids to form water-soluble complexes called micelles, within which lecithin and cholesterol can be transported from the liver. Bile salts are also detergents and a reduction in surface tension allows fat to be emulsified in the intestine, thus facilitating its digestion and absorption. On reaching the distal ileum, 95% of the bile salts are reabsorbed, transported back to the liver and passed once again into the biliary system. This enterohepatic circulation (Fig. 14.16) allows a relatively small bile salt pool (2–4 g) to circulate through the intestine some 6–12 times a day. The daily faecal loss equals that of hepatic synthesis (0.2–0.6 g/24 hrs). When bile is excluded from the intestine, 25% of ingested fat may appear in the faeces and there is marked malabsorption of fat-soluble vitamins, including vitamin K.

Fig. 14.16 The enterohepatic circulation.

The gallbladder has a capacity of 50 ml and can concentrate bile by a factor of 10. It contracts in response to cholecystokinin (CCK), which is released from the duodenal mucosa by the presence of food, notably fatty acids. Gallbladder contraction is accompanied by reciprocal relaxation of the sphincter of Oddi. The secretion of bile is promoted by the hormone secretin. The vagus nerve also stimulates bile secretion and gallbladder contraction. Some 1–2 litres of bile are produced by the liver daily.

Summary Box 14.4 Bile salts

• The primary bile acids, chenodeoxycholic and cholic acid, are conjugated with glycine or taurine and form sodium or potassium bile salts (e.g. sodium taurocholate)

• Bile salts are vital for the excretion of cholesterol in bile; cholesterol is insoluble in water and must be transported in water-soluble complexes (micelles) with bile salts and lecithin

• Bile salts are detergents, and on reaching the intestine they emulsify fat and facilitate the digestion and absorption of fat and fat-soluble vitamins

• Bile salts must not be confused with bile pigments (e.g. bilirubin), which are waste products and excreted in bile. The small bile salt pool (2–4 g) is conserved by reabsorption of bile salts from the terminal ileum

• Disease or resection of the terminal ileum prevents the enterohepatic circulation of bile and is associated with a high incidence of cholesterol gallstones and diarrhoea (owing to the cathartic action of bile salts on the colon).

Congenital abnormalities

Congenital abnormalities of the gallbladder and bile ducts are common. The gallbladder may be absent (agenesis), double, intrahepatic, partitioned with a fold in the fundus (Phrygian cap), or multiseptate. The cystic duct may be absent or join the right hepatic duct rather than the common hepatic duct, and accessory ducts may be present. The cystic artery may be duplicated or may arise from the common hepatic or left hepatic artery. These anomalies are important in that great care must be taken to avoid the inappropriate division of major ducts and arteries in the course of cholecystectomy.

Biliary atresia

Failure of development of the duct system occurs once in every 20 000–30 000 births and is the most common cause of prolonged jaundice in infancy. Jaundice usually becomes apparent in the first 2–3 weeks of life and the liver and spleen usually enlarge. LFTs show an obstructive pattern. Liver biopsy reveals cholestatic jaundice, but differentiation from neonatal hepatitis is often surprisingly difficult.

In extrahepatic biliary atresia, a Roux loop of jejunum is anastomosed to the intrahepatic duct system in the hilum of the liver (Kasai operation). A delay in treatment will result in jaundice and cholangitis, allowing cirrhosis to develop, with portal hypertension and ascites.

Choledochal cysts

Cystic transformation of the biliary tree (choledochal cyst) is rare. The most common type results in a saccular dilatation of the common bile duct, which often has an abnormal termination that enters the pancreatic duct within the head of the pancreas. This may allow reflux into the biliary system, resulting in pain, inflammation, calculus formation and malignant transformation. The abnormalities are probably congenital, although diagnosis may be delayed until adult life.

In the neonate, the cyst may present with jaundice or spontaneous perforation. The adult patient usually presents with intermittent pain and jaundice, and may have attacks of pancreatitis. LFTs show a cholestatic pattern, and ultrasonography and cholangiography (MRCP or ERCP) establish the diagnosis (Fig. 14.17). In view of the significant risk of malignant transformation, excision of the cyst is indicated.

Fig. 14.17 ERCP demonstrating the common type of choledochal cyst (CDC) involving the common bile duct.

Caroli’s disease consists of cystic biliary dilatation that is more marked in the peripheral intrahepatic ducts. Recurring infection may progress to cirrhosis and liver failure. When Caroli’s disease is found in association with congenital hepatic fibrosis, portal hypertension is often present. Endoscopic, percutaneous and surgical manipulation of the biliary tree is best avoided, and liver transplantation may have a valuable role in management.

Gallstones

Pathogenesis

Gallstones are common in Europe and North America but less so in Asia and Africa. Their incidence increases with age. In developed countries, they occur in at least 20% of women over the age of 40; the incidence in males is about one-third of that in females. The disease has increased markedly in frequency and cholecystectomy is the most common elective abdominal operation in many Western countries.

Gallstone formation results from an imbalance of the constituents of bile. The majority of stones result from an inability to keep cholesterol in micellar form in the gallbladder; pigment stones are less common. Most cholesterol stones become mixed with bile pigments as they increase in size; such ‘mixed’ stones are much more common than pure cholesterol stones.

Cholesterol stones

Cholesterol stones are particularly common in middle- aged obese multiparous women. Stone formation is encouraged if bile becomes supersaturated with cholesterol (i.e. lithogenic), either by excessive cholesterol excretion or by a reduction in the amount of bile salt and lecithin available for micelle formation. Supersaturation is most likely to occur as the bile is concentrated in the gallbladder, and is favoured by stasis or decreased gallbladder contractility. The formation of cholesterol crystals is the key event, and this ‘nucleation’ may be due to coalescence of cholesterol molecules or their precipitation around particles of mucus, bacteria, calcium bilirubinate or mucosal cells. Pure cholesterol stones are yellowish-green with a regular shape but rough surface. They are usually solitary, whereas mixed stones are darker and are usually multiple.

Cholesterol stones are particularly common in some tribes of North American Indians, where more than 75% of women over 40 are affected. Such individuals have a small bile salt pool. Conversely, the high incidence of stones in Chilean women reflects high levels of cholesterol excretion. Obesity and high-calorie or high-cholesterol diets favour cholesterol stone formation by producing highly supersaturated gallbladder bile. Drastic weight reduction and diets designed to lower serum cholesterol levels may also promote stone formation by mobilizing cholesterol and increasing its excretion.

Disease or resection of the terminal ileum and drugs such as cholestyramine favour cholesterol nucleation by reducing the bile salt pool. Hormonal influences are reflected in an increased incidence of stone formation in women taking oral contraceptives or post-menopausal oestrogen replacement. Pregnancy may also have an effect by increasing stasis within the gallbladder.

Pigment stones

Pigment stones consist of calcium bilirubinate and are usually multiple and small. They are more prevalent in those areas of the world where haemolytic blood disorders are most common: for example, Mediterranean countries and malarial regions. Stones found in Western patients are usually composed of black pigment, whereas brown pigment stones are common in people from the Far East. Pigment stones account for 25% of all gallstones in Western patients, but for 60% of those in some Far Eastern countries such as Japan.

Chronic haemolysis favours pigment stone formation by increasing pigment excretion, and stone formation is common in congenital spherocytosis, haemoglobinopathy and malaria. Cirrhosis and biliary stasis are also important associations. Some patients with brown pigment stones have increased amounts of unconjugated bilirubin in the bile. In Far Eastern patients, this may be due to the action of β-glucuronidase produced by E. coli, an organism that invades duct systems infested with Clonorchis sinensis or Ascaris lumbricoides.

Pathological effects of gallstones

Acute cholecystitis and its complications

This is usually produced by obstruction of the neck of the gallbladder or cystic duct by a stone resulting in a chemical inflammatory reaction. Bacteria are cultured from the bile in approximately one-half of patients with gallstones, and unrelieved obstruction in the presence of this infected bile may produce an empyema. The thickened gallbladder becomes intensely inflamed, oedematous and occasionally gangrenous. The fundus of the distended, inflamed gallbladder may perforate, giving rise to localized abscess formation and occasionally to biliary peritonitis. The common organisms implicated in inflammation of the gallbladder are E. coli, Klebsiella aerogenes and Strep. faecalis. Staphylococci, clostridia and salmonella are occasionally present. These organisms may be cultured from the blood if there isbacteraemia.

Chronic cholecystitis

Repeated bouts of biliary colic or acute cholecystitis culminate in fibrosis, contraction of the gallbladder and chronic inflammatory change with marked thickening of the wall. The gallbladder ceases to function. Chronic inflammatory change may be present in the absence of gallstones, as is the case in the gallbladders of typhoid carriers. The incidence of carcinoma of the gallbladder is increased in patients with long-standing gallstones.

Mucocoele

A mucocoele develops when the outlet of the gallbladder becomes obstructed in the absence of infection. The imprisoned bile is absorbed, but clear mucus continues to be secreted into the distended gallbladder.

Choledocholithiasis

When gallstones enter the common bile duct, they may pass spontaneously or give rise to obstructive jaundice, cholangitis or acute pancreatitis. Gallstone pancreatitis most commonly occurs when a small stone becomes temporarily arrested at the ampulla of Vater.

Gallstone ileus

This uncommon form of intestinal obstruction occurs when a large gallstone becomes impacted in the intestine. Stones large enough to block the gut generally gain access by eroding through the wall of the gallbladder into the duodenum.

Summary Box 14.5 Gallstones

• Most gallstones form because of failure to keep cholesterol in solution. This can result in pure cholesterol stones, but more commonly the stones also acquire a content of bile pigment as they enlarge, forming ‘mixed’ stones

• Pigment stones are the most common type of stone in some Far Eastern countries, but are less common in Western society, where they are associated with chronic haemolysis, biliary stasis and cirrhosis

• Only 15% of stones contain enough calcium to be seen on a plain film

• The majority of individuals with gallstones are asymptomatic and remain so; the presence of gallstones is not in itself an indication for cholecystectomy

• Gallbladder stones may cause flatulent dyspepsia, biliary colic, acute cholecystitis and gallbladder cancer (although the latter is so rare that this consideration does not affect the decision not to treat asymptomatic stones)

• Gallstones that migrate into the bile duct can cause obstructive jaundice, cholangitis and acute pancreatitis, although they often remain asymptomatic

• Gallstone ileus is a rare form of intestinal obstruction; stones large enough to obstruct the gut are usually too large to pass through the ampulla of Vater and have gained access to the gut by an internal fistula involving the gallbladder.

Common clinical syndromes associated with gallstones

The majority of individuals with gallstones are asymptomatic or have only vague symptoms of distension and flatulence. Less than a fifth of such patients develop symptoms or complications from their gallstones within 10 years.

Biliary colic

Biliary colic is due to transient obstruction of the gallbladder from an impacted stone. There is severe gripping pain, often developing after meals or in the evening, which is maximal in the epigastrium and right hypochondrium with radiation to the back. Despite being continuous, the pain may wax and wane in intensity over several hours, and vomiting and retching are common. Resolution occurs when the stone falls back into the gallbladder lumen or passes onwards into the common bile duct. The patient then recovers rapidly, but repeated bouts of colic are common. In some cases, the obstruction does not resolve and the patient develops acute cholecystitis.

Acute cholecystitis

Acute cholecystitis is a more prolonged and severe illness. It usually begins with an attack of biliary colic, although its onset may be more gradual. There is severe right hypochondrial pain radiating to the right subscapular region, and occasionally to the right shoulder, together with tachycardia, pyrexia, nausea, vomiting and leucocytosis. Abdominal tenderness and rigidity may be generalized but are most marked over the gallbladder. Murphy’s sign (a catching of the breath at the height of inspiration while the gallbladder area is palpated) is usually present. A right hypochondrial mass may be felt. This is due to omentum ‘wrapped’ around the inflamed gallbladder.

In 85–90% of cases, the attack settles within 4–5 days. In the remainder, tenderness may spread and pyrexia and tachycardia persist or worsen. The development of a tender mass, associated with rigors and marked pyrexia, signals empyema formation. The gallbladder may become gangrenous and perforate, giving rise to biliary peritonitis. Jaundice can develop during the acute attack. Usually, this is associated with stones in the common bile duct, but compression of the bile ducts by the gallbladder may be responsible.

Acute cholecystitis must be differentiated from perforated peptic ulcer, high retrocaecal appendicitis, acute pancreatitis, myocardial infarction and basal pneumonia. Acute cholecystitis can develop in the absence of gallstones (acalculous cholecystitis), although this is rare.

Summary Box 14.6 Acute cholecystitis

• In the great majority of cases acute cholecystitis is associated with gallstones and results from obstruction of gallbladder outflow

• In contrast to biliary colic, which results from obstruction alone, acute cholecystitis is associated with infection and is a systemic illness

• The patient appears unwell, has pyrexia and tachycardia, and is tender in the right hypochondrium; Murphy’s sign is almost always positive

• In 90% of cases, acute cholecystitis will settle with conservative treatment (nil by mouth, intravenous fluids, antibiotics, nasogastric suction if appropriate)

• In 10% of cases, disease progression leads to life-threatening complications: notably, empyema, gangrene and perforation

• Given that the gallbladder is permanently diseased and that complications may supervene, most surgeons now advocate early cholecystectomy (i.e. within 5 days) for acute cholecystitis.

Chronic cholecystitis

Chronic cholecystitis is the most common cause of symptomatic gallbladder disease. The patient gives a history of recurrent flatulence, fatty food intolerance and right upper quadrant pain. The pain is worse after meals and is often associated with a feeling of distension and heartburn. The differential diagnosis includes duodenal ulcer, hiatus hernia, myocardial ischaemia, chronic pancreatitis and gastrointestinal neoplasia. Symptoms for mucocoele are the same as those for chronic cholecystitis but a non-tender piriform swelling may be palpable in the right hypochondrium. There is little systemic upset and no pyrexia.

Choledocholithiasis

Stones may be present in the common bile duct of some 5–10% of patients with gallstones. There is little muscle in the wall of the bile duct, and pain is not a symptom unless the stone impedes flow through the sphincter of Oddi. The vast majority of stones in the common bile duct originate in the gallbladder. ‘Primary’ duct stones are extremely rare.

Impaction of a stone at the sphincter obstructs the flow of bile, producing jaundice, pale stools and dark urine. Obstruction commonly persists for several days but may clear spontaneously, as a result either of passage of the stone or of its disimpaction. Small stones may pass through the common bile duct without causing symptoms. In longstanding obstruction the bile ducts become markedly dilated and the diameter of the common bile duct may exceed its upper limit of 10 mm. A totally obstructed duct system becomes filled with clear ‘white bile’, as back pressure on the hepatocytes prevents clearance of bilirubin and mucus secretion is increased.

Infection of an obstructed biliary tract causes cholangitis, which is characterized by attacks of pain, pyrexia and jaundice (‘Charcot’s triad’), frequently in association with rigors. Long-standing intermittent biliary obstruction may lead to secondary biliary cirrhosis. Obstructive jaundice due to stones in the common bile duct has to be distinguished from other causes of obstructive jaundice, notably malignant obstruction and cholestatic jaundice. Acute viral or alcoholic hepatitis may occasionally be confused with obstructive jaundice.

Acute pancreatitis may be associated with a stone in the common bile duct (Ch. 15).

Courvoisier’s law

Fibrosed gallbladders that contain stones cannot distend when pressure increases in the obstructed biliary tree. Courvoisier’s law states that if the gallbladder is palpable in the presence of jaundice, the jaundice is unlikely to be due to stone. This law is not inviolate. Distended gallbladders are not always easy to feel but can be detected readily by ultrasound.

Other benign conditions of the gallbladder

Cholesterosis

Cholesterosis or ‘strawberry gallbladder’ is a condition in which the mucous membrane of the gallbladder is infiltrated with lipid and cholesterol. It affects middle-aged and elderly patients of either sex. Cholesterol stones are found in the gallbladders of half of these patients. Macroscopically, the mucosa is brick-red and speckled with bright yellow nodules. Management is as for chronic cholecystitis.

Adenomyomatosis

This rare condition is characterized by mucosal diverticula (Rokitansky–Aschoff sinuses) that particularly affect the fundus and penetrate the muscular layers to the serosa. Muscular hypertrophy and inflammatory cell infiltrates are present. The diagnosis may be made on careful imaging but is often only made following cholecystectomy, as the gallbladder normally contains stones.

Acute acalculous cholecystitis

Few patients with acute cholecystitis have acalculous inflammation. The condition may be precipitated by major surgery, bacteraemia, trauma, pancreatitis or other serious illness, and may complicate parenteral nutrition. The inflammatory reaction in the gallbladder wall may be intense and severe, leading to gangrene and perforation. In ill patients, percutaneous drainage (cholecystostomy) under ultrasound guidance may be considered, but urgent cholecystectomy is often advisable.

Investigation of patients with suspected gallstones

Blood tests

A full blood count may reveal a neutrophilia in acute cholecystitis or its complications. An elevated serum bilirubin or alkaline phosphatase may signify the presence of common duct stones. Prothrombin time should be measured if there has been a history of jaundice.

Plain abdominal X-ray

As only 15% of gallstones contain enough calcium to be seen on a plain radiograph, this investigation is not used in diagnosis. Gas is rarely seen outlining the biliary tree if there is a fistula between the biliary tract and the gut, as in gallstone ileus or following endoscopic sphincterotomy.

Ultrasonography

Ultrasonography permits inspection of the gallbladder, its wall and its contents, and demonstrates dilatation of the intrahepatic and extrahepatic biliary tree. Stones reflect the ultrasonic wave and are thrown into prominence by the acoustic shadow they produce (Fig. 14.18). The technique is extremely accurate in skilled hands. As it does not depend on hepatic excretion of contrast, it can be used in both jaundiced and non-jaundiced patients, and therefore has supplanted oral cholecystography.

Fig. 14.18 Ultrasound scan of the gallbladder demonstrating the hyperechoic features of a solitary gallstone (arrowed) along with the typical acoustic shadow.

Cholangiography

Intravenous cholangiography has been replaced by MRCP which is used increasingly to assess the biliary tree non-invasively whereas ERCP is reserved for removing common bile duct stones by endoscopic sphincterotomy. Complications occur in up to 7% of patients and may include cholangitis and pancreatitis.

Surgical treatment of gallstones

Patients with symptomatic gallstones are usually advised to undergo cholecystectomy to relieve symptoms and avoid complications (EBM 14.5). Patients with asymptomatic gallstones are treated expectantly, particularly if they are elderly or suffering from medical conditions likely to increase the risk of surgery. In younger patients, there may be a stronger case for surgery despite the absence of symptoms, particularly if the stones are multiple and likely to cause complications, such as acute pancreatitis.

14.5 Surgical treatment of gallstones

‘Asymptomatic gallstones do not require treatment by laparoscopic cholecystectomy unless there is a high risk of gallbladder cancer. Once a patient with gallstones becomes symptomatic, elective cholecystectomy is indicated. Laparoscopic cholecystectomy is associated with less pain, shorter hospital stay, faster return to normal activity and less abdominal scarring than open cholecystectomy. These advantages are also evident when the procedure is used in acute cholecystitis.’

NIH Consensus Statement 1992 Sep 14–16; 10(3):1–20. Kiviluoto T, et al. Lancet 1998; 351:321–325.

The principles of surgical treatment involve removal of the gallbladder and the stones it contains, while ensuring that no stones remain within the ductal system. ‘Open’ cholecystectomy has largely been replaced by laparoscopic cholecystectomy, but is still undertaken in up to 10% of patients with symptomatic gallstones and in patients in whom laparoscopic surgery cannot be completed safely. A laparoscopic procedure may not be possible in the patient who has previously undergone multiple abdominal operations but contraindications to laparoscopic surgery are few.

Conversion from a laparoscopic procedure to open cholecystectomy should be seen as a limitation of the minimally invasive technique and not as a failure of the surgeon. Laparotomy is mandatory when the anatomy in the area of the cystic duct and artery cannot be defined readily, if uncontrolled bleeding occurs, or if the bile duct is injured (EBM 14.6).

14.6 Complications of cholecystectomy

‘Conversion to an open procedure from a laparoscopic procedure should be considered in the presence of adhesions, difficulty in delineating the anatomy or a suspected complication. Injury to the bile duct during cholecystectomy requires immediate referral to a surgeon or service specialised in the management of such a complication.’

Connor S, Garden OJ. Br J Surg 2006; 93(2):158–168.

Open cholecystectomy

The gallbladder is usually approached through a right subcostal incision. Following careful inspection and palpation of the abdominal contents to exclude other pathology, the cystic duct and artery are identified. Intraoperative cholangiography is performed under image intensification by cannulating the cystic duct and following the injection of contrast. The cholangiogram displays the anatomy of the duct system, identifies ductal stones, and confirms that dye passes freely into the duodenum (Fig. 14.19). The cystic duct and artery are ligated and divided and the gallbladder is removed. A retrograde approach, in which the gallbladder is mobilized ‘fundus first’, can be used when inflammation makes visualization of the biliary anatomy difficult, and in difficult cases a subtotal cholecystectomy may avoid damage of vital structures. Some surgeons pursue a policy of selective cholangiography, obtaining a cholangiogram only in patients at high risk of having ductal stones. The presence of such stones may be suspected if there is a history of jaundice or pancreatitis, if preoperative LFTs are abnormal, or if dilatation of the common bile duct or the presence of multiple gallbladder stones has been detected on ultrasound.

Fig. 14.19 Operative cholangiogram undertaken at laparoscopic cholecystectomy (note the radio-opaque ports).

The extrahepatic ducts are seen and there is flow of contrast into the duodenum. A small radiolucent calculus is present at the lower end of the common bile duct (arrow).

Following removal of the gallbladder, haemostasis is secured and the wound closed. The value of routinely placing an abdominal drain has been questioned although its use in difficult surgery may prevent the development of a collection and identify leakage of bile.

Laparoscopic cholecystectomy

Access to the peritoneal cavity is obtained through three or four cannulae inserted through the anterior abdominal wall and following insufflation of the peritoneal cavity with CO₂. The gallbladder is retracted by grasping forceps inserted to display the structures at the porta hepatis. An excellent view of the operating field is obtained with the laparoscope (Fig. 14.20), and the cystic duct and artery are isolated by dissection with instruments passed through the remaining cannulae. Some surgeons have found it difficult to undertake operative cholangiography routinely with this approach, and have either abandoned its use or relied upon MRCP or selective ERCP in the pre- or postoperative period to exclude the presence of common bile duct stones.

Fig. 14.20 Laparoscopic view of the gallbladder attached to the main bile duct beneath the liver and showing the branches of the cystic artery (arrow) on the gallbladder surface.

The cystic duct and artery are divided between metal clips and the gallbladder is dissected from the liver using diathermy. Extraction of the gallbladder through a cannula site may require extension of the incision or the tedious removal of individual stones from the gallbladder. Care must be taken to secure haemostasis and ensure the absence of bile leakage at the end of the procedure.

Summary Box 14.7 Cholecystectomy

• Cholecystectomy is the standard treatment for symptomatic gallbladder stones; alternatives (stone dissolution, extracorporeal lithotripsy) are now seldom used

• Open cholecystectomy has been largely superseded by laparoscopic cholecystectomy, but conversion to open operation is still sometimes needed

• Cholecystectomy now has a low operative mortality (0.2%); inadvertent injury to the bile duct (0.2% incidence) remains the main source of major morbidity

• Some 5–10% of patients undergoing cholecystectomy have ductal stones, many of which are unsuspected. Opinions vary as to whether intraoperative cholangiography should be undertaken routinely to detect such stones

• In the era of laparoscopic cholecystectomy, there is a growing tendency not to perform routine operative cholangiography, and to extract symptomatic duct stones by non-operative means (i.e. at endoscopic papillotomy)

• If ductal stones cause symptoms, they frequently give rise to cholangitis and Charcot’s triad of pain, jaundice and fever (often with rigors).

Exploration of the common bile duct

This is undertaken much less often with the free availability of ERCP and sphincterotomy (EBM 14.7). At open surgery, if stones are present in the duct system, the common bile duct is opened between stay sutures (choledochotomy) and the stones are extracted with forceps or a balloon catheter. Following exploration, further check cholangiogram films are obtained, or the interior of the duct can be inspected with a fibreoptic choledochoscope. The opening in the common bile duct is closed around a T-tube, the long limb of which is brought out through a stab incision in the abdominal wall (Fig. 14.21). This serves as a safety valve to allow the escape of bile if there is a temporary obstruction to flow into the duodenum following duct exploration. It also facilitates a T-tube cholangiogram some 7–10 days following surgery. If this shows free flow of dye into the duodenum and no residual duct stones, the T-tube can be clamped before removal.

14.7 Exploration of the common bile duct

‘Patients undergoing cholecystectomy do not require ERCP preoperatively if there is a low probability of choledocholithiasis. Laparoscopic common bile duct exploration and postoperative ERCP are both safe and reliable in clearing common bile duct stones.’

Nathanson L, et al. Ann Surg 2005; 242:188–192.

Fig. 14.21 T-tube drainage of the common bile duct.

If, at operation, a stone is firmly impacted at the lower end of the common bile duct, it may have to be removed through the duodenum. Transduodenal sphincterotomy and sphincteroplasty increase the risk of postoperative morbidity and mortality, and are undertaken rarely. With the reluctance of some surgeons to perform operative cholangiography during laparoscopic cholecystectomy, increasing reliance has been placed on removing common bile duct stones at ERCP. Other surgeons continue to adhere to the principles employed at open cholecystectomy and explore the common bile duct by means of a choledochotomy or through the dilated cystic duct. Retained stones can be removed with the aid of a small-diameter fibreoptic choledochoscope under direct vision, or by means of a wire basket or an inflatable balloon catheter using the image intensifier. The surgeon can suture or leave a drain in the cystic duct, or can oversew the choledochotomy over a T-tube or stent.

Complications of cholecystectomy

The postoperative stay of patients undergoing open cholecystectomy may exceed 7 days. Respiratory complications are not uncommon and there is a significant risk of wound infection (see below). Operative mortality following elective open cholecystectomy is low (0.2%), but is increased tenfold if there is obstructive jaundice or if the common bile duct has to be explored.

Postoperative stay is reduced greatly with laparoscopic cholecystectomy, which in some centres is undertaken as a day-case procedure. Complications resulting from a major abdominal wound are undoubtedly avoided, but there is concern regarding the apparent increased incidence of injury to the bile duct. Failure of the patient to recover quickly following the procedure, the development of abdominal pain or the need for additional analgesia in the immediate postoperative period should cause the surgeon to consider the complications of haemorrhage or bile leakage, and mandates further assessment by LFTs, abdominal imaging or repeat laparoscopy. Mortality and morbidity related to the laparoscopic procedure have also been reported. Nevertheless, the advantages to the patient of this minimally invasive technique have led to its widespread adoption by surgeons.

Haemorrhage

This may originate from the cystic artery or the gallbladder bed. Significant intra-abdominal bleeding should be suspected from the development of pain or if the patient exhibits early features of hypovolaemic shock. Blood may issue from the drain, if one is present, and re-exploration is mandatory.

Infective complications

Wound infection from organisms present in the bile (notably E. coli, Klebsiella aerogenes and Strep. faecalis) can be reduced following cholecystectomy by the intravenous administration of a cephalosporin at the time of induction of anaesthesia, although the routine use of this group of drugs at laparoscopic cholecystectomy has recently been questioned (EBM 14.8). A longer course of antibiotics may be prescribed when significant bile contamination of the peritoneal cavity has occurred at surgery. Collections of bile and/or blood readily become infected after cholecystectomy. Formal drainage may be needed if this progresses to the formation of a subhepatic or subphrenic abscess.

14.8 Antibiotic prophylaxis in laparoscopic cholecystectomy

‘Routine prophylactic administration of antibiotics is unnecessary in patients at low risk of wound or postoperative infection.’

Al-Ghnaniem R, et al. Br J Surg 2003; 90(3):365–366.

14.9 Timing of cholecystectomy

‘Early cholecystectomy for acute cholecystitis is associated with a better outcome than delayed cholecystectomy.’

Papi C, et al. Am J Gastroenterol 2004; 99(1):147–155.Shikata S, et al. Surgery 2005; 35:553–560.

Bile leakage

This may be due to a ligature or clip slipping off the cystic duct, the accidental division of an unrecognized accessory duct, damage to the common bile duct, or retention of a duct stone after exploration. Bile leakage may be evidenced by the development of abnormal LFTs and localized or generalized abdominal pain. It may be contained if a drain is in place. In the absence of biliary peritonitis, a persistent leak requires investigation by means of endoscopic cholangiography. Surgery may be needed if biliary peritonitis develops.

Retained stones

Following bile duct exploration, any retained small stones evident on the postoperative T-tube cholangiogram (see above) may be flushed into the duodenum by irrigating the T-tube with saline. Their passage may be facilitated if glucagon is given to relax the sphincter of Oddi. If the duct cannot be cleared by irrigation, delayed extraction of the stones may be undertaken under radiological control. The patient is discharged with the T-tube in place. This is removed 4–6 weeks later and a steerable catheter passed along its track into the bile duct. A wire (Dormia) basket can be passed along the catheter to catch and withdraw the retained calculus (Fig. 14.22).

Fig. 14.22 Removal of a retained common bile duct stone.

In some patients, unsuspected stones may be left in the bile duct at cholecystectomy. Such stones usually give rise to complications such as jaundice, cholangitis and pancreatitis in the months and years following cholecystectomy. Ultrasonography and MRCP can be used to confirm the presence of such retained stones (Fig. 14.23) and endoscopic retrograde cholangiography and sphincterotomy are performed to recover them (Fig. 14.24). In this technique, a diathermy wire attached to a cannula is passed through the duodenoscope and used to divide the sphincter of Oddi. The stones can then be extracted with a Dormia basket or balloon catheter. This same method can be used to extract stones detected in the immediate postoperative period. If the stones are too large to be withdrawn or the patient is unwell, a stent or a catheter can be left in the biliary system (nasobiliary catheter). The stones can be crushed (lithotripsy) and removed at a later date by means of a repeat endoscopic examination. Surgery may be required to retrieve retained bile duct stones that cannot be dealt in this way.

Fig. 14.23 Endoscopic retrograde cholangiography demonstrating multiple stones (arrows) within the biliary tree.

These calculi were removed from the dilated bile duct by balloon extraction following sphincterotomy.

Fig. 14.24 Endoscopic papillotomy to remove retained stones.

Bile duct stricture

About 90% of benign duct strictures result from damage during cholecystectomy, in which the duct is divided, ligated or devascularized. This last mechanism appears to be a common cause of injury at laparoscopic cholecystectomy. Other causes of injury include division of a ligated common bile duct that has been mistaken for the cystic duct, division of the right hepatic duct below the point of anomalous insertion of the cystic duct, and encirclement of the common bile duct by the ligature or clip used to close off the cystic duct. Strictures only occasionally result from abdominal trauma or erosion of the bile duct by a gallstone impacted in the gallbladder (Mirizzi’s syndrome).

If the common bile duct is completely occluded, progressive obstructive jaundice develops in the postoperative period. If there is a partial stricture, attacks of pain, fever and obstructive jaundice signal the development of cholangitis. The serum alkaline phosphatase and transaminase concentrations are usually elevated, and blood cultures may be positive during attacks of fever. If left untreated, persistent cholangitis and obstruction progress to hepatic abscess formation and rarely to secondary biliary cirrhosis.

The site and extent of the stricture must be defined radiologically. After ultrasonography has been performed, MRCP, ERCP and/or PTC are undertaken. Reconstructive surgery is carried out in a specialist centre and usually necessitates bringing up a Roux loop of jejunum and anastomosing this to the distended biliary system above the stricture (Fig. 14.25).

Fig. 14.25 Relief of bile duct stricture by anastomosis of a limb of jejunum to the distended biliary tree above the stricture (hepaticojejunostomy Roux en Y).

Post-cholecystectomy syndrome

This term is used to embrace a group of complaints such as post-prandial flatulence, fat intolerance, epigastric and right hypochondrial discomfort, and heartburn, which may follow cholecystectomy. The complaints tend to be more troublesome when cholecystectomy has been performed in the absence of gallstones. Investigations are usually negative, but some patients prove to have retained stones or other alimentary disorders such as peptic ulceration, gastritis and chronic pancreatitis. It is possible that some patients develop pain because of functional abnormalities of the sphincter of Oddi (see below).

Management of acute cholecystitis

Patients with acute cholecystitis are admitted to hospital, to be monitored, and analgesics, intravenous fluid and a broad-spectrum antibiotic such as a cephalosporin are prescribed. Patients are given nothing by mouth and a nasogastric tube is passed only if they are vomiting. The majority of patients settle within a few days on this regimen. Failure to settle suggests the presence of an empyema.

Some surgeons delay operation for 2–3 months after the attack in the expectation that the acute inflammatory reaction will have resolved by then, but most now prefer to perform cholecystectomy during the same admission and within 72 hours of the onset of the attack (EBM 14.9). Provided the operation is carried out by an experienced surgeon and under antibiotic cover, ‘early’ cholecystectomy is not associated with an increased incidence of complications. The duration of the illness and hospitalization is reduced, and further attacks of acute cholecystitis during the waiting period for elective surgery are averted. It should be noted that this is a planned procedure carried out after appropriate investigation (ultrasonography) and with all facilities, on a scheduled list. Laparoscopic cholecystectomy is more difficult to perform in the acute setting, but is the method preferred by most surgeons.

If surrounding inflammation makes identification of the relevant anatomical structures difficult, drainage of the gallbladder with removal of stones (cholecystostomy) may be performed as an interim measure. Elective cholecystectomy is usually performed approximately 2 months later.