Primary Biliary Cirrhosis

Primary biliary cirrhosis, or chronic nonsuppurative destructive cholangitis, usually affects middle-aged women. Asymptomatic individuals may be diagnosed during routine examination, where they are found to have hepatomegaly, elevated autoantibodies, or elevated plasma alkaline phosphatase. The earliest symptom is usually pruritus, even before clinical jaundice is apparent, but later the patient may develop overt jaundice; hepatosplenomegaly; xanthelasma, especially in the palms and around the eyes; vitiligo; and arthritis. Primary biliary cirrhosis often is found in association with connective tissue disease.

Ulcerative Colitis and Crohn Disease

Ulcerative colitis and Crohn disease are associated with hepatobiliary disorders, especially primary sclerosing cholangitis (see Chapter 41). It is important to include a detailed gastrointestinal systems review and investigations in any patient with unexplained liver disease.

Budd-Chiari Syndrome

This syndrome is characterized by venous outflow obstruction to the liver, which could be intrahepatic or extrahepatic (see Chapter 77). Acute venous obstruction is usually secondary to another pathologic process and presents with abdominal pain, vomiting, hepatomegaly, ascites, and jaundice, which may be mild. Hepatocellular failure leading to death is usually rapid. Chronic venous obstruction of the liver usually presents with ascites and hepatomegaly. If the inferior vena cava (IVC) is blocked with tumor or thrombus, gross edema of the legs and superficial venous distension of the abdominal veins is apparent. Diagnosis is made on imaging.

Hemochromatosis

Hemachromatosis is an iron overload state in which the liver is usually affected. Excess iron deposition leads to fibrosis and cirrhosis with an increased risk of developing hepatocellular carcinoma. Clinically, hemochromatosis usually presents between the ages of 40 and 60 years. Symptoms are usually nonspecific with lethargy, increased pigmentation, loss of body hair, loss of libido, arthralgia, and diabetes, usually due to the involvement of the pancreas. Clinical examination may show hepatomegaly and hyperpigmentation in the axillae, groins, and genitalia as well as testicular atrophy. Diagnosis is made by hematologic tests including serum iron, serum ferritin, and serum transferrin; liver damage can be assessed with a liver biopsy.

Polycystic Disease

Symptoms of polycystic disease are usually caused by the mass effect of the enlarged liver (see Chapter 69A). Abdominal distention and breathlessness are common. Early satiety and vomiting can occur because of pressure on the stomach. Acute abdominal pain is usually due to infection or bleeding into a cyst.

Acute Liver Failure

Acute liver failure (ALF) is characterized by massive cellular injury to a previously healthy liver, and it is associated with the development of hepatic encephalopathy (see Chapter 72). This can occur as a result of paracetamol (acetaminophen) toxicity, usually caused by overdosage, or from a massive viral infection. ALF is associated with a high mortality and requires careful monitoring. Orthotopic liver transplantation is the only effective treatment for this condition, although some cases of ALF can recover spontaneously. Donor organ shortage has dictated the development of criteria that can help to predict whether a patient with ALF has a potential to recover or whether a liver transplant is required. More recently, these criteria have also been used to predict the prognosis of patients with cirrhosis undergoing surgery for hepatocellular carcinoma (Kuang et al, 2009). Various sets of criteria have been proposed, of which the Model for End-Stage Liver Disease (MELD) and the King’s College Hospital (KCH) criteria are the best known. Most criteria utilize prothrombin time/INR, serum bilirubin, serum creatinine, arterial blood pH, and hepatic encephalopathy in categorizing patients’ disease severity.

Liver Masses

Patients with large liver masses may be seen initially with right upper quadrant discomfort or a palpable mass in the upper abdomen. More often, liver masses are discovered during imaging as part of the investigation of jaundice, nonspecific abdominal symptoms, or follow-up of malignancy. If the liver mass is discovered incidentally, a full clinical history should be obtained with particular attention to gastrointestinal and respiratory symptoms. Details and duration of oral contraceptive and anabolic steroid use should be recorded. Relevant past history, especially of other malignancies, should be obtained, and the possibility of viral hepatitis should be considered. A thorough abdominal examination should be performed, especially for abnormal masses and ascites, and a digital rectal examination is mandatory at the initial assessment. Signs of jaundice, liver insufficiency, and development of collateral circulation should be sought. A comprehensive hematologic and biochemical screening (Table 12.3) should include an assessment of coagulation factors and of common tumor markers (α-fetoprotein, carcinoembryonic antigen (CEA), CA 19-9, CA 125). Cross-sectional imaging evaluation of liver masses is discussed later in this chapter (see Investigation of Hepatobiliary Disease; see also Chapters 16 and 17).

Table 12.3 Laboratory Investigations in Hepatopancreatobiliary Disease

Gallbladder

Tenderness and guarding in the right hypochondrium exacerbated by inspiration (Murphy sign) suggests cholecystitis. If the gallbladder is palpable in the presence of obstructive jaundice, this suggests malignant obstruction of the biliary tree (Couvoisier’s law), which is commonly due to carcinoma in the head of the pancreas. Failure to palpate the gallbladder does not exclude malignant disease, however, and a nonpalpable gallbladder is the rule in malignant obstruction at the hilus of the liver. A gallbladder that is intermittently palpable suggests the presence of a periampullary carcinoma (Kennedy & Blumgart, 1971). Gallbladder distension and signs of sepsis in the presence of gallstones may indicate empyema of the gallbladder. In such instances, initial treatment consists of percutaneous aspiration and drainage, with a cholecystectomy delayed for some time.

Acute Cholecystitis

Acute cholecystitis may begin with a constant dull ache that slowly increases in severity over time, usually a couple of days, and may be associated with anorexia, nausea and vomiting, and pyrexia. It arises as the result of acute inflammation of a distended, obstructed, and usually infected gallbladder (see Chapter 31). Patients may be more comfortable lying still because of the associated localized peritonitis, and coughing or sneezing may exacerbate the pain. Acute cholecystitis is often associated with tenderness (peritoneal irritation) in the right upper quadrant and signs of systemic infection (pyrexia, raised leukocyte count, raised C-reactive protein), and it requires antibiotic therapy to settle the infection. An infected, obstructed gallbladder sometimes ruptures and causes generalized peritonitis or a liver abscess. It is important to examine patients with acute cholecystitis regularly, and if the pain and tenderness do not settle rapidly with antibiotic therapy, percutaneous drainage of the gallbladder or an emergency cholecystectomy may be required.

Biliary colic, which is a clinical entity distinct from acute cholecystitis, usually has a crescendo-decrescendo pattern, with the pain slowly building up to a peak over a few hours; this peak is often associated with vomiting, and the pain then gradually subsides over the ensuing few hours. Often the pain radiates to the back (Berhane et al, 2006), and this pattern of gallbladder pain is thought to arise from gallbladder nociceptors, in response to a rise in intracholecystic pressure caused by strong contraction of the gallbladder against an obstructed neck. Biliary colic usually settles spontaneously, leaving some residual soreness in the right upper quadrant. These attacks of pain can be widely variable in their occurrence, and some patients may have an interval of many years between attacks; others may have almost constant discomfort. Some patients report that the pain is triggered by certain foods, usually fatty foods, and some patients are afraid of eating for fear of triggering an attack of pain (sitophobia).

Cholelithiasis

Symptomatic cholelithiasis is the commonest indication for cholecystectomy. Unfortunately, the symptomatology of gallbladder stone disease has been hard to define despite research spanning decades (Johnson & Jenkins, 1975; see Chapter 30). A large epidemiologic investigation in Denmark into the relationship between abdominal symptoms and gallstones concluded that the predictive values of various abdominal symptoms for gallstones were very low. In patients with gallstones, the prevalence of right upper quadrant abdominal pain was similar to patients without gallstones but was higher in patients who had previously undergone cholecystectomy (Jorgensen, 1989). A larger, multicenter Italian study, MICOL, showed that in an Italian population, the presence of epigastric or right upper quadrant pain radiating to the right shoulder that forced the patient to rest and intolerance to fried or fatty food were good predictors of gallstones (Corazziari et al, 2008). A recent Swedish study that followed up 503 patients without gallstones for 5 years reported that the incidence of gallstone formation was 1.39 per 100 person-years, and that no change was seen in the symptoms of these patients before and after development of gallstones (Halldestam et al, 2009).

Studies examining the relief of symptoms after cholecystectomy suggest that approximately one quarter of patients undergoing cholecystectomy will not experience relief of symptoms, and that dyspeptic symptoms are least likely to be cured by cholecystectomy (Weinert et al, 2000; Jorgensen et al, 1991). A study comparing the symptomatic outcomes after cholecystectomy for functioning and nonfunctioning gallbladders showed no difference in outcome (Larsen et al, 2007). An important study outlined the variation in perceptions of what was considered a valid indication for cholecystectomy (Scott & Black, 1991). These authors showed the case histories of 252 patients to two panels, one comprising surgeons and the other a mixed panel of doctors. The mixed panel considered 41% of the operations appropriate for the indications and 30% inappropriate, but the surgeons considered 52% appropriate and 2% inappropriate but could not agree on the other 46%. It is therefore important that an accurate documentation of dyspeptic or atypical symptoms be made, and patients should be counseled that cholecystectomy may not relieve any of their symptoms.

Biliary Obstruction

Classically, pain is a discriminating feature in jaundiced patients. Patients with biliary tract obstruction resulting from tumor usually have painless jaundice (see Chapters 50A through 50D and Chapter 58B), whereas patients with an acute attack of pain or a long history of intermittent episodes of jaundice accompanied by pain frequently have gallstone disease (see Chapter 35). In the event of cholangitis, rigors and fever also are present. Jaundice unaccompanied by pain, and especially if the gallbladder is palpable, almost always indicates malignancy. Back pain usually indicates a pancreatic lesion; chronic pancreatitis and tumors of the pancreas can manifest in this manner. Patients with chronic pancreatitis occasionally are seen with jaundice, especially during an acute-on-chronic attack, and the jaundice may be accompanied by symptoms of endocrine and exocrine deficiency (diabetes, steatorrhea, malabsorption; see Chapter 55A).

Malignant disease affecting the hepatic ducts at the biliary confluence in the hilus of the liver often presents with jaundice (Fig. 12.9), but in such instances, the gallbladder is not palpable (see Chapter 50B). Itching can be an initial feature of biliary obstruction (Fig. 12.10), but in prolonged cholestasis, itching may occur in association with partial biliary obstruction and significantly in primary biliary cirrhosis. Alkaline phosphatase often is markedly increased in partial biliary obstruction, even though the bilirubin may be only marginally elevated. A markedly increased or increasing alkaline phosphatase level may be the only sign of an early malignant or benign biliary stricture.

FIGURE 12.9 This patient initially presented with obstructive jaundice resulting from hilar cholangiocarcinoma. She had lost a great deal of weight and was anorexic and had intermittent attacks of cholangitis. Treatment was extended right hepatic lobectomy with excision of the biliary confluence and hepaticojejunostomy with Roux-en-Y to the left hepatic ducts. Four years later, she shows an excellent result: no tumor recurrence, normal liver function tests, and the patient has gained weight.

FIGURE 12.10 A, Patient with severe itching associated with primary biliary cirrhosis. She is scratching her back with a wooden back scratcher. B, Severe excoriation of the legs caused by scratching in a woman with severe itching resulting from primary biliary cirrhosis.

The distinction between obstructive (surgical) jaundice and hepatocellular (medical) jaundice is seldom the problem it was in the past. Hematologic and biochemical tests of liver function (Table 12.4) usually indicate whether the jaundice is obstructive, but this is not always the case. Identification of the cause and level of biliary obstruction is essential. Ultrasound (Chapter 13) is the preferred initial imaging test for diagnosis of biliary obstruction and to determine the etiology and level of obstruction. Computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP; see Chapters 16 and 17) are also extremely useful for evaluation of biliary obstruction.

Acalculous Biliary Pain

Acalculous biliary pain is considered to be the result of a “functional” motor disorder of the gallbladder and/or sphincter of Oddi (Behar et al, 2006). Gallbladder motor dysfunction giving rise to abdominal pain has been defined by the Rome II Committee on Functional Biliary and Pancreatic Disorders as episodes of severe, steady pain located in the epigastrium and right upper quadrant and all of the following: episodes last 30 minutes or more, symptoms have occurred on one or more occasions in the previous 12 months, the pain is steady and interrupts daily activities or requires consultation with a physician, no evidence of structural abnormalities explains the symptoms, and gallbladder function is abnormal with regard to emptying. To eliminate calculous disease from the differential diagnosis, the Rome II Committee recommendations in the evaluation of these patients includes screening tests: upper gastrointestinal endoscopy, liver biochemisty, pancreatic function tests, and ultrasound of the gallbladder should be normal, and microlithiasis of bile should be excluded by endoscopic aspiration at endoscopic retrograde cholangiopancreatography (ERCP) or by aspiration of bile from the duodenum after stimulation by cholecystokinin (CCK) or magnesium sulfate. The recommended tests for gallbladder function are CCK cholescintigraphy assessment of gallbladder emptying, CCK- or meal-stimulated ultrasonographic volumetry of the gallbladder, and CCK-induced pain provocation tests. The Committee recommended that abnormal gallbladder emptying after CCK stimulation (<40% ejection) is an acceptable indication for cholecystectomy, as medical therapies are usually not effective (Corazziari et al, 1999).

Unfortunately, no consensus exists regarding the infusion rate of CCK that in turn can directly influence gallbladder emptying. Delgado-Aros and colleagues (2003) and DiBaise and Oleynikov and colleagues (2003) reported meta-anlayses of studies examining the symptomatic benefit from cholecystectomy based on abnormal CCK-stimulated gallbladder emptying. They found no good evidence to support the use of CCK-stimulated gallbladder ejection fraction to select patients for cholecystectomy. Similar findings were reported by Rastogi and colleagues (2005). Smythe and colleagues (1998) conducted a critical evaluation of CCK-provoked gallbladder pain and concluded that this test was not a predictor of symptomatic relief after cholecystectomy. It is interesting to note that in a prospective randomized study examining the development of symptoms in patients with uncomplicated gallbladder stones, a CCK-stimulated ejection fraction greater than 60% was independently associated with the development of symptoms.

The etiology and pathogenesis of calculous and acalculous gallbladder pain are poorly understood despite some recent insights by mathematical modeling (Li et al, 2007, 2008; Bird et al, 2006; Wegstapel et al, 1999; Ooi et al, 2004; Ahmed et al, 2000). We would therefore currently recommend that patients experiencing recurrent and severe symptoms as defined by the Rome II criteria should be offered cholecystectomy but should be carefully counseled regarding the uncertainty of its outcome, and this counseling should be clearly documented.

Sphincter of Oddi Dysfunction

Sphincter of Oddi (SO) dysfunction may be present in patients with an intact biliary tree, but it usually comes to light as a potential diagnosis when symptoms continue after a cholecystectomy. SO dysfunction has been subclassified into a biliary or pancreatic type. Biliary type SO dysfunction in postcholecystectomy patients has been arbitrarily subclassified into types I, II, and III. Type I SO dysfunction is defined as pain, elevated liver function tests documented on two or more occasions, delayed contrast drainage, and a dilated common bile duct with a corrected diameter of 12 mm or more at endoscopic retrograde cholangiopancreatography (ERCP). Type II SO dysfunction is characterized as pain only with one or two of the criteria in Type I. Type III SO dysfunction is defined as recurrent biliary-type pain with none of the criteria from type I. Toouli (2009) concluded that accurate sphincter manometric data is crucial to establish a diagnosis of SO dysfunction. Invasive investigation of sphincter dysfunction and/or sphincterotomy is associated with a risk of pancreatitis in up to 30% of patients. Insertion of prophylactic pancreatic stents are advocated as a means of reducing this risk, and some evidence exists to support this practice. Injection of botulinum toxin into the sphincter also has been advocated as a “therapeutic test” before a sphincterotomy is performed. In a literature review, Sgouros and Pereira (2006) concluded that biliary sphincterotomy reliably treats symptoms in 85%, 69%, and 37% of patients with types I, II, and III SO dysfunction, and pancreatic sphincterotomy may benefit up to 75% of patients. They state that sphincter manometry is the gold standard in the investigation. Pancreatic type SO dysfunction is also subclassified into types I, II, and III according to whether pancreatic enzymes are elevated soon after an attack of pain and whether the pancreatic duct is dilated greater than 5 mm.

Iatrogenic Biliary Injury

Patients with iatrogenic damage to the biliary tract (see Chapter 102) may not only present with jaundice because of biliary stricture but also may present with biliary leakage, resulting in biliary peritonitis or fistula. In such patients it is important to obtain a good history that includes a copy of the original operative report, which may offer an indication as to the level and nature of the injury and may provide a baseline for comparison with further investigations. Many patients may present with biliary and abdominal sepsis, and blood and bile cultures should be obtained. If a biliary fistula is present, or if the patient is deeply jaundiced, coagulation may be deranged. Liver function tests may show biochemical evidence of biliary obstruction or of liver damage, and patients are often nutritionally depleted and may be anemic. Ongoing liver damage may be present, resulting from a combination of sepsis and biliary obstruction.

Imaging with CT and MRCP may yield valuable information in these patients. MRCP can accurately depict areas of stricture and fistula formation, and CT can be used to guide intervention and drainage. The key question is whether the biliary tract is intact and in continuity. In patients with a biliary fistula, fistulography may outline the problem; but ERCP and percutaneous transhepatic cholangiography are more useful, because they provide a dynamic view of the site and show the severity of leakage, which may allow a stent to be placed across the site of the leak. Associated vascular injuries should be suspected and may be suggested at imaging. Extensive bleeding at the time of cholecystectomy should lead to a high index of suspicion for vascular injury. Hepatic arterial injury is usually well compensated, and portal venous injury may be revealed by the presence of liver atrophy, usually best seen on CT. Occasionally, long-standing biliary strictures result in secondary biliary cirrhosis, and liver biopsy may be necessary.

Acute Pancreatitis

Acute pancreatitis is usually accompanied with severe upper abdominal pain that develops rapidly, becomes constant, and persists for several hours (see Chapter 53). The pain typically starts in the epigastrium but may soon spread throughout the abdomen and radiate into the back. Sometimes the patient may find relief by sitting forward, but usually they lie still and curled up in bed. The pain can be so sudden in onset that at times, it can simulate a perforated peptic ulcer, and indeed acute pancreatitis can mimic almost every cause of acute abdominal pain and may even produce chest pain that simulates myocardial infarction, pneumonia, or pleurisy. Frequent vomiting and sequestered fluid in the small bowel may lead to rapid and severe dehydration. Even keeping the stomach empty with a nasogastric tube may not prevent the patient from retching, and marked nausea is almost a constant feature. Hiccoughs can also occur due to diaphragmatic irritation secondary to extension of the inflammatory process tracking up via the retroperitoneum.

Patients with acute pancreatitis may exhibit signs of profound shock with tachycardia, tachypnea, hypotension, and confusion. At the other extreme, patients may appear well, with little in the way of physical signs. The patient may be afebrile on admission, but progression of the inflammatory process leads to fever, facial flushing, and mild jaundice. Abdominal examination usually reveals marked tenderness in the epigastrium with guarding, but marked rigidity as seen in a perforated ulcer is often lacking. The presence of a paralytic ileus may result in abdominal distension with a tympanitic percussion note and diminished bowel sounds. Later features may include a discoloration around the umbilicus (Cullen sign) or in the flanks (Grey-Turner sign) as a result of bruising within the fascial planes, pancreatic ascites, and a pleural effusion. A mass is rarely present, unless the inflammatory process has resulted in a pancreatic abscess or sizeable pseudocyst. General features of acute pancreatitis may include confusion, disorientation, hypoxemia, and even adult respiratory distress syndrome. The associated hypocalcemia rarely results in clinical signs of neuromuscular irritability.

Rarely, acute pancreatitis can occur without severe pain, and in these cases, the diagnosis can be missed, and such failure may be associated with a poor prognosis (Lankisch et al, 1991). It is important to be aware of the condition and consider it in any patient who develops sudden shock or anuria, especially if it follows biliary surgery, ERCP, coronary artery bypass, or trauma. A detailed history is therefore vital, particularly inquiring as to the past medical history and family history, especially in children. Any history of alcohol abuse, bilary colic, jaundice, recent surgery, or ERCP should be actively sought.

Most cases of acute pancreatitis are associated with alcohol abuse or biliary disease but can also follow ERCP; abdominal surgery, especially to the stomach, duodenum, and biliary tree; coronary artery bypass surgery; trauma; and certain viral illnesses, especially mumps. The association with alcohol abuse varies according to country and urbanization, being as high as 65% in parts of urban America. Biliary disease is responsible for over 30% of cases in a general population, and sieving the feces of patients with gallstone-associated pancreatitis shows gallstones present in a high proportion of them (Kelly, 1976), prompting many to speculate that the pancreatitis resulted from the temporary lodging of a stone in the ampulla of Vater. Postoperative pancreatitis accounts for 5% to 10% of cases (Thompson et al, 1988), and hyperamylasemia can occur in about 10% of patients undergoing ERCP, although only 1% will develop severe acute pancreatitis. The cause of traumatic pancreatitis is again subject to geographical variation (Jones, 1985); penetrating trauma is more common in the United States and blunt trauma and injury as a result of traffic accidents are more common in the United Kingdom. Other rare causes include hyperparathyroidism, hyperlipidemia, and certain drugs including steroids, azothiaprine, and diuretics (Nakashima & Howard, 1977). However, once all these causes have been excluded, for about 25% of patients, no clear etiology is identified. The sex ratio for acute pancreatitis is virtually equal but tends to have a higher peak age incidence in women, reflecting the higher incidence of gallstones; in men the lower peak age reflects their propensity to alcohol abuse.

Chronic Pancreatitis

There are few pathognomonic or diagnostic signs for chronic pancreatitis, and diagnosis usually depends on the history and special investigations (see Chapter 55A). The patient may appear malnourished with signs of weight loss, they may be icteric as a result of compression of the common bile duct by the fibrotic process in the head of the pancreas, and erythema ab igne may be present on the back or abdomen. Uncommonly, a palpable mass, pseudocyst, or splenomegaly may be evident, and occasionally pancreatic ascites, if there has been rupture of a pseudocyst or of the duct system.

Chronic pancreatitis is a difficult condition both to diagnose and to treat. It is crucial to exclude other associated conditions, such as pancreatic cancer; but once the diagnosis is established, it is important to 1) identify any predisposing cause, 2) stage the severity of the disease, and 3) document any morphologic and functional changes against which any progression can be assessed. One of the commonest predisposing factors is alcohol abuse, although chronic pancreatitis is also associated with biliary disease, congenital abnormalities such as an annular pancreas (Dowsett et al, 1989), ductal abnormalities, and rarely with hyperparathyroidism. An autosomal dominant hereditary form of the condition may also be a factor, so a family history is crucial (Teich, 2008). Rarely is any specific drug or dietary factor implicated.

Pain is the commonest presenting symptom of chronic pancreatitis and is often the most difficult to control. The pain is usually situated in the epigastrium and subcostal regions and commonly radiates through to the back. Pain can be severe and penetrating in nature, and often the patient will lean forward or curl up to relieve the discomfort. In severe cases, the patient may even kneel on all fours to gain relief. Occasionally, the pain may radiate to the left shoulder tip. Variation in the pattern of pain in these patients is enormous, and some are never free of discomfort, but others may simply complain of intermittent attacks. In some, these severe bouts may be brought on by eating or ingesting alcohol, although often no clear association is made between attacks and oral intake. In many the pain is so debilitating that it interferes with the patient’s domestic, social, and occupational activities and can have a devastating impact on the quality of life. Indeed, in many it results in a change in personality with a manipulative tendency often associated with an addiction to opiates. These patients can be particularly difficult to assess, especially if they are already addicted to alcohol.

Other presenting symptoms include marked steatorrhoea resulting from diminished lipase production and inadequate fat absorption (Di Magno, 1982). The stool frequency may be increased up to six times a day, and the stools themselves become pale and bulky with an offensive odor, and they float, making them difficult to flush away. However, this is not a constant feature of chronic pancreatitis; some patients may even suffer from constipation as a result of the increased use of opiate analgesia.

The incidence of diabetes mellitus is a variable and often late feature. As chronic pancreatitis progresses, there may be loss of endocrine function, initially requiring dietary control and subsequently oral hypoglycemic agents or even insulin. Other more general features of chronic pancreatitis may include weight loss, nausea and vomiting, jaundice, and even gastrointestinal bleeding as a result of splenic vein thrombosis, although this is rare.

Pancreatic Cancer

Regretfully, physical signs of pancreatic cancer are often absent or infrequent, until the lesion is unresectable (see Chapter 58B). The patient may be symptomatic with weight loss, but unless the lesion is situated in the head of the pancreas such that it obstructs the common bile duct early, causing obstructive jaundice, few other signs may be evident. With distal bile duct obstruction, the gallbladder may become distended (Courvoisier gallbladder). An abdominal mass and ascites are late signs and usually herald inoperability. Systemic signs such as flitting thrombophlebitis migrans may be apparent, but this is uncommon and nonspecific. All too often cachexia is the only physical finding.

Later clinical features of pancreatic cancer are pain, weight loss, and jaundice. The pain is often severe and gnawing and radiates to the back. It is often worse at night, when the patient is lying flat, which usually indicates tumor extension to the retroperitoneum, often signifying irresectability. Weight loss may be marked, and in many cases of tumors in the body of the pancreas, weight loss may be the only symptom, until pain indicates invasion of the peripancreatic tissue. The more rapid the weight loss, the less likely the lesion is to be resectable (Bakkevold et al, 1992). Jaundice can be associated with severe pruritus, but this classical presentation only occurs when the lesion is in the head of the pancreas; when jaundice occurs with tumors of the body or tail of the pancreas, it usually signifies hilar liver or nodal metastases.

About 5% of patients with pancreatic cancer will have developed diabetes mellitus within the 2 years prior to diagnosis (Pannala et al, 2009). Other signs such as ascites, an epigastric mass, or enlarged supraclavicular nodes (Virchow sign) are indications of inoperability. Because of the lack of specific signs and symptoms, very commonly a diagnostic dilemma arises as to whether a lesion is chronic pancreatitis or pancreatic cancer. Frequently, diagnostic imaging cannot provide the answer, and even at operation it may not be apparent which condition the surgeon is facing; this occured in up to 15% of cases in some series (Mao et al, 1995).

Colorectal Liver Metastases

Liver metastases from primary colorectal cancer are frequently discovered at the time of diagnosis on the staging CT scan (see Chapter 81A). Metastases may occasionally be detected during operation on the primary tumor, especially if this is done as an emergency procedure. They are also frequently discovered as metachronous tumors during follow-up after resection of primary colorectal cancer. Follow-up strategies in patients with colorectal cancer are a subject of much debate, and no clear consensus exists. In patients with no perioperatively detected metastatic disease and an R₀ colonic resection, it is advisable to image the chest, abdomen, and pelvis with contrast-enhanced CT scan at 9 months and 2 years postresection. If metachronous liver metastases are detected, resectability is determined by the patient’s ability to undergo potentially major liver surgery by the location and segmental distribution of the hepatic metastases and by the presence of extrahepatic disease. Positron emission tomography (PET) and CT scan can be most useful in this regard (see Chapter 15). Recent reports have shown added benefit of contrast-enhanced MRI scan to determine resectability (Blyth et al, 2008; Hekimoglu et al, 2009). Synchronously detected liver metastases may be resected at the time of the resection of the primary lesion or as a second procedure, sometimes after the administration of neoadjuvant chemotherapy.

It is important to note that metastatic disease in the liver, especially in its early stages, may not give rise to symptoms and can only be detected by screening these patients. Regular serum CEA levels are useful in the follow-up of these patients, and combined with interval CT scanning, this should detect the majority of colorectal liver metastases.