Benign and malignant diseases of the hepatobiliary system
The biliary system
Bile duct obstruction causing jaundice and cholangitis is frequently encountered in surgical practice. Most often this is due to gallstones or pancreatic malignancy.
Primary diseases of the bile duct are individually uncommon. When considered overall, they are however a significant cause of bile duct obstruction.
Anatomical and functional considerations
The biliary tree is a conduit for the passage of bile from the hepatic biliary cannaliculi to the duodenum. Because of a paucity of muscle in the bile duct wall there is little peristaltic action except in the ampullary segment. This segment controls the flow of bile into the duodenum and acts as a barrier to proximal migration of the duodenal contents.
The bile duct develops embryologically from the ventral hepatic bud of the foregut. There are numerous anatomical variants in the branching structure of the bile duct. These lead to differences in the segmental biliary anatomy, which have important surgical implications. Such variations may increase the risk of biliary injury during cholecystectomy (Biliary variations increasing the risk of biliary injury: (A) Normal; (B) low-entry posterior sectoral duct; (C) short cystic duct and (D) sectoral duct drainage into gall bladder.).
Abnormalities of the bile duct will produce obstructive jaundice or cholangitis or both.
In clinical practice, differentiation from hepatocellular jaundice due to drugs, toxins or infection is the first priority. The clinical features of biliary obstruction include pale stools, dark urine and itch, and are usually diagnostic. If jaundice is episodic or associated with pain, rigors and pyrexia, then obstruction is highly likely. Fluctuating jaundice indicates intermittent obstruction from a stone or polypoid peri-ampullary cancer. Loss of weight is a strong indication of malignancy and is a common feature of pancreatic cancer.
Biliary fistula, either external or into the peritoneal cavity, is a feature produced by biliary trauma, either iatrogenic or following penetrating injury. Collection of bile in the peritoneal cavity does not necessarily produce pain unless the bile is infected, in which case biliary peritonitis may occur. Large-volume fistulae will produce significant fluid and electrolytic loss and, when prolonged, nutritional problems from fat malabsorption. Spontaneous closure of low-volume fistulae may occur unless there is distal biliary obstruction.
Biliary disease in childhood
Congenital biliary anomalies such as atresia or choledochal cyst, usually present in early childhood. Occasionally, choledochal cysts will have a delayed presentation until adult life and rarely will present in middle age. Biliary malignancy is not seen in childhood, but gallstones are occasionally seen and are more common after major illness or injury.
Primary sclerosing cholangitis (PSC) is associated with inflammatory bowel disease. This will produce intermittent or progressive jaundice, and the biliary disease may occasionally pre-date the intestinal symptoms. Like most biliary diseases, it may also produce pancreatitis either due to bile duct stone formation or from stricturing of the ampullary segment of the bile duct. Choledochal cysts and PSC are both strongly associated with the development of cholangiocarcinoma.
Chronic biliary obstruction associated with persistent low-grade infection may be a precursor to biliary malignancy. Biliary cirrhosis leading to liver failure and portal hypertension is a late feature of chronic obstruction.
In the jaundiced patient, laboratory investigations should include haematological tests, clotting profile and standard liver function tests. The abnormalities of liver function demonstrate an obstructive pattern, with invariable elevation of the alkaline phosphatase and y-glutamyl transpeptidase (GGT). If an obstructive pattern is seen, the next step is abdominal ultrasound, which is the key diagnostic test. This test will be followed by a variety of more invasive investigations, depending on the results obtained.
Ultrasound is widely available, cheap, non-invasive and able to determine the presence of obstruction by demonstrating biliary dilatation. In experienced hands, it can show the level of obstruction. The detection of space-occupying lesions in the liver, porta hepatis or pancreas will depend on the body habitus of the patient and will also be affected by the amount of surrounding intestinal gas. Stones in the gall bladder are easily seen, although stone detection in the bile duct is less reliable.
Endoscopic retrograde cholangiopancreatography
Endoscopic injection of contrast into the biliary and pancreatic ducts is an accurate method of demonstrating biliary obstruction and determining its cause (Endoscopic retrograde cholangiopancreatography showing stricture due to biliary carcinoma.). Endoscopic retrograde cholangiopancreatography (ERCP) can be combined with interventional techniques such as:
- tumour cytological brushings or biopsy
- sphincterotomy and stone extraction
- insertion of stents to overcome biliary obstruction
Percutaneous transhepatic cholangiography (PTC)
Radiological injection of contrast into the intrahepatic bile ducts is preferable to ERCP when the ampulla is inaccessible, or when previous biliary surgery has transected the bile duct. This procedure may also be combined with complex interventional techniques to overcome biliary obstruction, either temporarily or as permanent palliation for malignancy.
Computed tomography (CT) is an accurate method of diagnosis for all forms of hepatobiliary disease. It can detect both intra- and extra-hepatic focal mass lesions and may be able to differentiate benign from malignant tumours. By combining CT with intravascular contrast injection, greater diagnostic accuracy can be achieved by demonstrating hepatic and portal vessels, and by increasing the difference in attenuation between lesions and the surrounding normal structures.
Computed tomographic cholangiography
More recently, with advances in computer technology, CT cholangiography has been introduced into clinical practice. Intravenous contrast material is administered to provide non-invasive opacification of the bile duct. The limitation is that in a patient with bilirubin greater than twice the normal level, biliary opacification will not be obtained. However, this technique has largely replaced ERCP when used for purely diagnostic purposes in a non-jaundiced patient.
Magnetic resonance cholangiopancreatography (MRCP)
Magnetic resonance can provide useful imaging of the liver, particularly by outlining the vascular anatomy. Recent technical advances have occurred in which MR can now be used to accurately image the bile ducts, even in jaundiced patients. A three-dimensional biliary reconstruction is possible, which is particularly useful as a pre-operative diagnostic tool for hilar malignancies and is helpful in assessing resectability.
Operative cholangiography and choledochoscopy
Operative cholangiography and choledochoscopy are useful in selected patients during biliary surgery. Cholangiography is usually carried out by placing a catheter through the cystic duct, although direct needle puncture of a bile duct can also be used. Choledochoscopy can be performed with either rigid or flexible instruments. Some dilatation of the bile duct is necessary, however, to allow passage of these instruments.
Nuclear scanning of the liver has largely been replaced by other modalities. Using hepatobiliary agents labeled with nuclear isotopes, such as hepatobiliary 99m Tciminodiacetic acid (HIDA), biliary imaging can be obtained and is particularly useful for defining the site of leakage in a biliary fistula. This test is ineffective when there is significant biliary obstruction.
Narrowing of the extrahepatic bile duct is most often due to malignancy in surrounding organs, with the tumour extending into or compressing the ducts. Primary malignancy of the pancreas, gall bladder, duodenum, liver or nodal disease in the porta hepatis are all more common than primary biliary malignancy (cholangiocarcinoma).
Benign strictures are most often the result of inadvertent damage to the bile duct during cholecystectomy and may occur immediately or after a delay of up to 10 years from operation. Benign strictures may also occur in PSC or in complex stone disease.
Adenocarcinoma of the bile duct is a rare tumour occurring most commonly after the age of 60 years. It can also occur in young patients and is more common in males. The tumour usually arises at the biliary confluence (Klatskin tumour). Presentation is with painless obstructive jaundice, and macroscopically the tumour is a sclerosing mass up to 4 cm in diameter. Characteristically, the tumour invades locally into surrounding blood vessels, nerves and the liver substance. Vascular occlusion is frequent and will lead to segmental or hemilobar atrophy of the liver.
Adenocarcinoma at the distal end of the bile duct is more often polypoid and is associated with a better prognosis as it is more often resectable.
Although cholangiocarcinoma can occur in patients with PSC or choledochal cyst, in Western countries no cause is usually found for this disease. It is, however, more common in Southeast Asia and this is probably due to the high prevalence of helminthic infection of the biliary tree.
Although slow growing, this tumour is highly lethal and most patients die within a few months of diagnosis. In selected patients resection is possible in specialised units and will lead to approximately 30% survival at 3 years.
When resection is not possible because of the patient's condition or the extent of the tumour, either palliative bypass surgery or endoprosthetic stent insertion is used to relieve jaundice. Stenting is more difficult than for low bile duct obstruction and results are less predictable.
Recently, radiotherapy has been used intraluminally to treat this disease. Iridium brachytherapy has been used as an adjunct to palliative surgery with encouraging results.
Benign strictures most commonly result from iatrogenic damage to the bile duct at the time of cholecystectomy. Less commonly, such strictures may follow blunt external biliary trauma, usually from motor accidents. Rare causes of benign strictures include atresia of the biliary tree in neonates and PSC, a condition associated with ulcerative colitis in adults. The latter results in multiple intra- and extrahepatic strictures that may mimic carcinoma. The condition may be associated with malignant transformation.
Benign post-cholecystectomy strictures occur after approximately 1 in 350 cholecystectomies. The introduction of laparoscopic cholecystectomy resulted in an increase in the rate of duct injury. With greater experience, the duct injury rate has steadily declined.
Injuries to the duct occur due to misinterpretation of the biliary anatomy. They are more common in inexperienced hands and in association with acute inflammation of the gall bladder where Calot's triangle is obliterated. They tend to occur in young patients particularly when the bile ducts are of a narrow calibre.
In the surgical dissection of the cystic duct, the common bile duct is inadvertently divided and a variable segment of the common hepatic duct is often removed, leading to either high occlusion of the ducts or biliary fistula. Common presentation following such an injury is either with bile drainage through a drain tube or bile peritonitis. Large volumes of bile in the peritoneal cavity may however be painless when the bile is sterile.
Late presentation after biliary injury is with jaundice. This may occur when the initial injury is incomplete or is due to ischaemia from diathermy damage of the biliary vasculature or ducts.
TREATMENT OF BENIGN STRICTURES
In the majority of patients, benign strictures should be treated by surgical intervention. Many of these patients are young and stenting would at best produce temporary relief of obstruction. Biliary reconstruction after duct injury involves anastomosing a defunctioned limb of jejunum, that is, a Roux-en-Y loop to the proximal biliary tree. This will lead to excellent results when early intervention is undertaken in an expert centre. The complexity of the reconstruction depends both on the size of the ducts involved and the proximal extent of the duct injury. With very high injuries, results are less certain and anastomotic restricturing will occur in approximately 20% of cases. This can usually be dealt with, without resorting to further surgery by percutaneous dilatation carried out through the Roux-en-Y loop using radiological techniques.
Primary sclerosing cholangitis is a relapsing, remitting condition and treatment is often nonsurgical. Stenting and dilatation may provide initial improvement. Late surgical intervention with either bypass, dilatation or liver transplantation will be necessary in severe cases.
In Western countries, biliary infection results from intestinal bacteria ascending into the bile duct secondary to biliary obstruction. In Asia, intrahepatic infection and stone formation are common, a condition called cholangiohepatitis. It is believed, although not proven, that the high incidence in Asia is due to the increased incidence of helminthic infection within the biliary tree.
Several species of liver fluke are known to infect humans. Fasciola hepatica is widespread but is mainly found in South America and parts of Europe. The adult worms infest cattle and sheep, and man is an accidental host infected by eating raw vegetables. The worm lives in the biliary tree and its presence produces fibrosis and, in severe cases, cholangitis and abscess.
A more common parasite is Clonorchis sinensis. This fluke is endemic in East Asia and infection occurs by eating raw fish. The adult worm migrates up the bile duct and usually dies there, causing obstruction, infection and stone formation. The presence of the fluke may lead to an increased incidence of cholangiocarcinoma.
Infection with Ascaris lumbricoides is common in Asia, Africa and Central America. Infection is via the faecal-oral route and the adult worm inhabits the small intestine. It may migrate up the bile duct causing cholangitis, pancreatitis or stone formation. The worms are large and may be seen on ultrasound or at ERCP. Worms may spontaneously migrate back into the intestine but they may also die within the bile ducts, causing obstruction.
Congenital biliary anomalies
Although considered congenital anomalies, biliary atresia and choledochal cyst may both be acquired conditions occurring or developing within the first few weeks of life.
Biliary atresia presents in the first few weeks of life. It is thought that an inflammatory process from an unknown cause affects the bile duct in the newborn infant. There is variable destruction of the extrahepatic bile ducts, causing obstructive jaundice and liver failure. Surgical correction of this abnormality before 8 weeks of age produces the best outcome.
Other anomalies associated with biliary atresia include intestinal malrotation and genitourinary anomalies. An aberrant communication between the biliary and pancreatic ducts has been reported in association with the condition, but it is not clear whether this is aetiologically important. Correction of this condition is by hepaticojejunostomy when a segment of extrahepatic duct is patent, or by porto-enterostomy for the more common severe case. In the latter operation, a jejunal Roux-en-Y loop is anastomosed to the porta hepatis after excision of the atretic duct remnants in the porta. Liver transplantation is frequently required for severe cases and atresia is the commonest indication for paediatric transplantation. Excellent long-term results are achieved with transplantation.
Cystic dilatation of the intra- or extrahepatic ducts is a rare condition, usually presenting before the age of 16 years. In 20% of cases, presentation is in adult life. Symptoms produced by the cyst include cholangitis, pancreatitis, stone formation and jaundice. Infants may occasionally present with an abdominal mass. The cause of this condition is debated. Anomalous communication between the biliary and pancreatic ducts is frequently found, but a degree of distal biliary obstruction may also be aetilogically important in the development of the cyst.
Cysts are classified according to their site and shape, although 80% are fusiform abnormalities of the extrahepatic bile duct (Classification of choledochal cysts (after Todani, Alonso-Lej).). Type II cysts are extremely rare.
The preferred surgical method of treatment is complete cyst excision with biliary reconstruction, because of the risk of malignant transformation if the cyst is left in situ. The rate of malignant transformation may be as high as 25% for untreated cysts. When multiple intrahepatic cysts are present complete excision may not be possible and treatment consists of producing good biliary drainage by excising any extrahepatic component.
Whether motility disorders of the sphincter of Oddi can produce pain syndromes is controversial. Manometric measurements on the sphincter muscle may be carried out at the time of ERCP to demonstrate high pressure contractions and retrograde peristalsis, which may produce symptoms in susceptible individuals. This is usually seen in young women. Documentation of biliary dilatation, obstructive abnormality of liver function during attacks, and provocation of attacks with known agents causing biliary spasm will support the diagnosis.
Treatment by antispasmotics, endoscopic sphincterotomy or, occasionally, surgical sphincteroplasty, have all been used in this difficult group of patients with varying success.
Surgical treatment of biliary disease
Patients who are jaundiced are often coagulopathic, have increased risk of infection, and are susceptible to renal failure in the presence of hypovolaemia. Important measures in the pre-operative period include correction of any clotting disorders by administration of intravenous vitamin K or fresh frozen plasma.
Aggressive rehydration to maintain circulation and urine flow is important to reduce the risk of renal failure. Prophylactic antibiotics are essential to prevent intra- and post-operative bacteraemia. Anaesthetic monitoring during operation will include measurement of urine output and central venous pressure. In very ill patients, a Swan-Ganz catheter to measure the right heart pressure may be necessary.
Accurate and complete pre-operative investigation will minimize the surgical difficulties encountered during the operative procedure. The standard approach to the bile duct is a right subcostal incision, which may be extended across the midline when access is difficult.
The bile duct is exposed at the free edge of the lesser omentum and intra-operative cholangiography may be performed through the cystic duct after removal of the gall bladder. The bile duct is identified by needle aspiration of bile, and stay sutures are inserted before the duct is opened axially. For access to the biliary confluence, the junction of Glisson's capsule at the base of the quadrate lobe (segment IV) and the anterior peritoneum of the portal structures are divided, exposing the left hepatic duct, which always lies extrahepatically.
Exploration of the bile duct may be performed with a variety of minimally traumatic instruments and choledochoscopy may be performed with either a rigid or a flexible endoscope. If tumours are resected, or if a distal obstruction is being bypassed, the duct is anastomosed, usually to a defunctioned loop of jejunum. In elderly patients, the bile duct may also be anastomosed to the duodenum (choledochoduodenostomy) in circumstances where there is distal biliary obstruction or concern about retained gall stones.
The pre-operative risks, including coagulopathy and renal dysfunction also pertain to the post-operative period. Continued fluid balance monitoring and repeated assessment of renal function are essential. Liver function will often temporarily worsen after surgery. Patients with sepsis will need aggressive antibiotic therapy, and may need care in an intensive care unit. Wound healing in a jaundiced patient is delayed and adequate nutrition must be achieved either by parenteral or enteral feeding.
Drain tubes are almost invariably used after biliary surgery and are removed once it is clear that no biliary leakage has occurred. If a T-tube is in situ, a check cholangiogram is carried out approximately 1 week after surgery. Patients are often discharged with a T-tube in place, and the tube is removed on the first post-operative visit.
Many advances in endoscopic approaches to the bile duct have occurred in the past 30 years. Endoscopists may now perform palliative stent insertion, stricture dilatation, stone extraction or tumour biopsy, and brushings for cytology. The limitation of stents used for palliating malignant obstruction is their short period of patency, usually less than 2 months. Plastic stents were used initially but have now been largely replaced by expandable metal stents with a diameter of up to 1 cm. These are associated with a longer period of patency but cannot be removed and should not be used where surgery might later be necessary.
Endoscopic stents are the preferred choice in elderly or frail patients and in patients with extensive malignant disease.
All the above procedures performed endoscopically can also be carried out using a transhepatic approach by radiologists skilled in biliary interventional techniques. The transhepatic approach does carry a risk of bleeding and biliary fistula, but is more appropriate when endoscopic access is not possible or is difficult. Where obstruction is segmental or lies high within the biliary confluence, percutaneous procedures are often more accurate than those performed endoscopically because of the ability of the radiologist to select the most appropriate ductal segment for intervention.
Percutaneous approaches may be combined with surgical reconstructive procedures, where access to the biliary tree can be obtained by a puncture of the Rouxen- Y loop that has been fixed to the deep surface of the abdominal wall. Such percutaneous transjejunal cholangiography (PTJC) is particularly useful in patients with benign strictures where dilatation may be necessary repeatedly, or where stents can be placed when there is recurrence of tumour after previous biliary surgery.
Treatment of biliary disorders involves a multimodality approach with collaboration between the radiologist, endoscopist and surgeon. This produces the optimum outcome for the patient. For complex conditions, combined approaches are best carried out in major hepatobiliary units where all such expertise is available.
Benign liver tumours
Adenomata are benign tumours that have a solid appearance on ultrasound or computed tomography (CT) scans and can present acutely with intraperitoneal rupture and bleeding. They have a strong association with the oral contraceptive pill and may regress following cessation of the pill. They probably have some malignant potential and if they show progressive increase in size on serial imaging studies, should be removed for this reason. Apart from the risk of malignancy, the major concern is their tendency to rupture with massive haemorrhage; therefore, this condition must be considered in young women presenting with abdominal pain, signs of hypovolaemic shock and features of haemoperitoneum. After resuscitation, the treatment is resection of the affected liver segment.
Focal nodular hyperplasia
Focal nodular hyperplasia (FNH) is not a true neoplasm but is probably due to a fibrous reaction to vessel ingrowth. Again, it is most common in young women. It has a characteristic central stellate scar on CT due to fibrous septae.
Macroscopically, it appears as a nodular firm vascular mass. Histologically, it may resemble cirrhosis with regenerating nodules and connective tissue septae. There may be symptoms of right upper quadrant pain. No specific treatment is required and the main purpose of management is to distinguish the lesion from neoplasms.
Haemangioma is the most common benign liver tumour and is cavernous in nature, with fibrous septae and a well-defined capsule. The tumours may again be related to the oral contraceptive pill and may regress when the pill is stopped. They may also enlarge during pregnancy. Most are asymptomatic but they can present as a mass lesion or with spontaneous haemorrhage. Contrast CT is diagnostic with peripheral then central infilling of the tumour with contrast, giving a halo and then target appearance. Magnetic resonance imaging (MRI) is also of value, as the T2-weighted image appearances are characteristic. These modalities now mean that biopsy is unnecessary. Biopsy can precipitate catastrophic bleeding and is strongly contraindicated.
Most haemangiomas require no treatment except radiological surveillance. Pain or enlargement may herald rupture and in these circumstances the tumour should be enucleated or the involved liver segment resected.
Focal fatty change
Focal fatty change can occur in the liver, particularly in obese patients and in those with diabetes mellitus. This is not a true tumour but can be confused with one, although a CT scan or an MRI shows a characteristic appearance.
Malignant liver tumours
Primary hepatocellular cancer or hepatoma
More than 300 cases of hepatocellular cancer (HCC) occur in Australia each year. It is a very common cause of cancer death in China and in Africa (up to 100 per 100,000 each year). In these countries the tumours have a very close relationship to hepatitis B surface antigen (HBsAG) positivity, with underlying cirrhosis, which increases the risk at least 200-fold. In Western countries, alcoholic cirrhosis is present in at least 90% of cases. It is clear that immunisation against hepatitis B virus and control of alcoholism offer a major opportunity to reduce the incidence of this highly malignant tumour. There are also associations with haemochromatosis and excessive intake of anabolic steroids. There is a slightly increased incidence with the oral contraceptive pill.
Hepatocellular cancers are adenocarcinomas that are frequently multicentric, often softer than the surrounding liver and can be difficult to distinguish from regenerative nodules in the cirrhotic liver. Spread is local to structures such as the diaphragm and distant to sites such as the lung and bone. A fibrolamellar type is seen mainly in young women and has a much better prognosis.
As with any cancer, HCC can present with clinical features of the primary tumour or of secondary deposits, or with the general features of malignant disease. The specific clinical features of the primary tumour can include pain, jaundice due to biliary compression or replacement of liver tissue, and haemorrhage due to oesophageal varices, sometimes precipitated by portal vein thrombosis. Intraperitoneal rupture and bleeding can occur. The diagnosis may be established before the onset of symptoms following screening for HCC using the serum α-fetoprotein (α-FP) test in cirrhotics, whether they be alcoholics or HBsAG-positive.
Investigations for primary HCC are given in Investigations for primary hepatocellular carcinoma
Liver resection can be undertaken, provided there is no disease outside the liver, there is sufficient reserve of liver function, the lesion is less than 5 cm in diameter and a curative resection with a 1 cm margin is possible. Operative mortality of liver resection for HCC, at approximately 10%, is much greater than for liver metastases because of the reduced liver function and limited ability of the cirrhotic liver to regenerate. Postoperative liver failure is the principal risk, and bleeding and sepsis are also frequently seen. The types of liver resection are covered later.
The very well differentiated variant of HCC, fibrolamellar carcinoma, is much less likely to spread outside the liver, and good results of transplantation have been described. Transplantation is also of value in small HCC with poor liver function due to their cirrhosis.
The ability of lipiodol (iodised poppy seed oil; an old radiological contrast agent) to be concentrated in HCC when administered through the hepatic artery can be used to treat HCC by selectively delivering a cytotoxic agent (adriamycin or cisplatin) or radiation (using 131I) to the cancer. Approximately 75% of HCC take up lipiodol and, of these, more than 50% will achieve at least a tumour marker (α-FP) response. Radiological evidence of shrinkage occurs somewhat less frequently. Variations in tumour response are seen; some patients remain tumour-free for several years after this type of therapy.
Percutaneous injection of absolute alcohol under ultrasound control can destroy small HCC. This is clearly an attractive non-operative option that may produce a cure. The best results are achieved in lesions of 2-cm diameter or less.
The prognosis of HCC is very poor, with a median survival of untreated symptomatic patients being approximately 3 months. For the comparatively small number of patients who are suitable for resection, 5-year survival is approximately 20%. It is hoped that this level of success will rise with more effective screening of at-risk patients.
Secondary liver cancer
The liver is frequently involved in the advanced stages of many different tumours and, while palliation of symptoms may be achieved, there are a few situations where very prolonged survival or even cure can be achieved. Specific forms of metastasis are susceptible to definitive treatment. For example, the occasional melanoma patient will have only a solitary liver metastasis that can be treated by resection. Very occasionally, patients with solitary metastases from other cancers (e.g. stomach, breast, sarcomas) have been cured by resection, but in the vast majority the possible benefit of resection is limited by the presence of disease outside the liver.
Some other types of tumour in which treatment can be of value will be considered in more detail.
Liver metastases from neuroendocrine tumours
This is one form of tumour where surgery has much to offer the patient with liver metastases. Metastases may be responsible for hormone secretion and particular syndromes (see Endocrine tumours of the pancreas), so that control of those metastases by debulking or resection can be of great benefit, although not necessarily prolonging life.
There are a number of surgical options:
- Transplantation. This can be done if there are very large numbers of lesions (melon seed liver). Results are good provided there is no disease outside the liver.
- Resection. Very extensive surgery is justified by long survival and good palliation.
- Cryotherapy. This gives encouraging results as measured by tumour markers, radiology and long-term survival.
- Embolisation. This is sometimes useful in palliation of symptoms for quite prolonged periods.
Colorectal cancer is the most common cause of cancer death in non-smokers in most of the developed world. Liver metastases are a common cause of death but, importantly, are the only site of metastatic disease in a significant number of patients. Regular serum carcinoembryonic antigen (CEA) tests after resection of primary colorectal cancers allows early diagnosis of liver metastases. In patients with unresectable disease, treatment is palliative for symptoms such as pain. The disease is potentially curable by resection if there is no extrahepatic disease, there are fewer than four metastases and the lesions are anatomically resectable with a 1-cm resection margin.
Investigations to be carried out are largely those defined for HCC (Investigations for primary hepatocellular carcinoma), with serum CEA levels in place of α-FP. As with HCC, the investigations are directed towards assessing liver function and the presence of disease beyond the potential limits of resection.
Curative treatment of liver metastases
Resection of up to two-thirds of the healthy liver is possible and is relatively safe, with an operative mortality of well under 5%. Factors that increase operative risk include jaundice, cirrhosis, significant concomitant medical disease of the heart or lungs, very extensive hepatic resections and the need for resection of the vena cava. Age alone is not a strong risk factor. Liver resection can now be done frequently without the need for blood transfusion because of:
- a better understanding of intrahepatic vascular anatomy (Liver segments. RHV, right hepatic vein; MHV, middle hepatic vein; LHV, left hepatic vein.)
- inflow occlusion (temporary occlusion of blood flow into the liver)
- the use of an ultrasonic aspirator (CUSA), which is a surgical instrument with a vibrating tip driven by an ultrasound transducer, used with a flow of fluid to dissect through the liver, allowing almost bloodless hepatic dissection
- intra-operative ultrasound, which allows precise identification of lesions, vessels and their relationship
- total vascular exclusion of the liver; clamping the outflow (hepatic veins) as well as the inflow allows rapid bloodless hepatic surgery.
The liver was divided into eight segments by a French anatomist, Cuinaud (Liver resection.). Segment I is the caudate lobe, just in front of the inferior vena cava. Segments II/III are the left lateral segment, to the left of the falciform ligament. Segment IV is also part of the left liver and is between the entry of the falciform ligament and the gall-bladder fossa. Segments V-VIII comprise the right lobe and are divided by vessels. All segments can be removed independently but the common resections are: right lobectomy V-VIII, left lobectomy II-IV, left lateral segmentectomy II, III, and extended right hepatectomy = right lobectomy + IV (Liver resection.).
Specific complications of liver resection include:
- Haemorrhage. This is usually due to a surgical cause (e.g. a clip or tie that has fallen off) and is easily corrected. Occasionally haemorrhage is secondary to coagulopathy, with many oozing sites due to inadequate liver function. Disseminated intravascular coagulation is usually a result of sepsis.
- Sepsis. This is usually in the form of a local abscess due to bile leak or infected haematoma, and is treated by a radiologically placed drain.
This technique allows some patients with lesions that are unresectable to be treated and does not require excision or destruction of much normal liver. A liquid nitrogen probe device is used and freezing monitored by intra-operative ultrasound. A 5-year survival of 20% in patients with unresectable disease has been seen. Other methods of imaging-controlled destruction include percutaneous placement of laser fibres and radio frequency (RF) destruction. These less invasive techniques may offer similar results.
Hepatic pain is controlled by analgesia and by steroids to reduce distension of the liver capsule. Radiotherapy may halt the progression of rapidly enlarging and painful liver metastases. Systemic chemotherapy has a limited effect.
REGIONAL OR HEPATIC ARTERY CHEMOTHERAPY
There is now good evidence from controlled trials to show that chemotherapy in the form of 5-fluorouracil or 5-fluorodeoxyuridine (FUDR) administered via the hepatic artery may extend life in patients with inoperable liver metastases. Patients with extrahepatic disease do not benefit from this treatment. A small implantable catheter system is placed in the gastroduodenal artery, with the tip of the catheter in the common hepatic artery. The gall bladder is removed to prevent cytotoxic cholecystitis. The catheter is connected to either a subcutaneous port that is accessed by needle and connected to an external pump system, or a totally implantable pump.
The advantages and disadvantages of hepatic artery chemotherapy over systemic chemotherapy are given in The advantages and disadvantages of hepatic artery chemotherapy over systemic chemotherapy.
HEPATIC ARTERY EMBOLISATION
Hepatic artery embolisation, using a radiologically placed catheter and gelfoam or steel coils, has been advocated for advanced liver metastases to palliate a large painful liver. This technique relies on the principle that the metastases have a predominantly arterial supply, while normal liver derives a higher proportion of its blood supply from the portal veins. Hepatic arterial embolisation will often induce considerable regression of metastasis but does not significantly affect the function of the normal liver.
SIRT (Selective internal radiotherapy)
This treatment utilises radioactive yttrium labelled particles which are given by hepatic artery injection, selectively delivered to tumour because of its principally arterial supply as opposed to the portal venous supply to the hepatic parenchyma. An injection of vasoconstructor further increases selectivity because tumour vessels do not contain smooth muscle. Although high response rates are seen, this does not control systemic disease.