The investigation plan

The investigation of incidentalomas is a two-stage process. The first stage is non-invasive and includes a thorough review of the clinical history and examination with particular focus on the organ systems and the most likely disease processes (see Box 26.1). Disease risk factors and symptom patterns may suggest a particular diagnosis or disease process and may help focus the diagnostic plan. A thorough physical examination, including a careful and complete examination outside the system involved looking for signs of primary or secondary involvement elsewhere, may similarly shorten the time to diagnosis.

After this review and focusing of the history and clinical examination, a few simple, non-invasive investigational tests will be indicated. These stage 1 investigations are usually non-specific, including an office urine analysis (urinalysis), a full blood count and general biochemical screen (liver function tests, urea, creatinine and electrolytes). More specific investigations should be evidence-based and used selectively as the field of diagnostic possibilities is progressively narrowed. Non-invasive specific disease investigations may include tumour marker and immunological studies or endocrine assays looking for the evidence of products secreted by the mass.

Clarification of anatomical details and differentiation of cystic from solid are crucial imaging issues, but may not have been possible on the original scan due to lesion size, scan quality or scan type and technique. Simple cysts are frequent incidental findings on abdominal imaging, especially in the liver and kidneys, but are also commonly seen in the pancreas and small bowel mesentery and less frequently in the pancreas and adrenals. Ultrasound scanning is adequate for assessment of most simple cysts. CT and ultrasound are often complementary to one another in the phase of non-invasive investigations.

Simple cysts rarely require further investigation or treatment. Parasitic cysts, posttraumatic cysts and pseudocysts need careful assessment, although not all will require treatment. All solid or mixed solid and cystic lesions require investigation to exclude neoplasia although only a few will be malignant.

Other non-invasive contrast radiology techniques such as barium meal, small bowel series, barium enema, magnetic resonance cholangiopancreatography (MRCP), CT cholangiography and nuclear scans may also be useful in diagnosing the nature of an incidentally detected abdominal mass, as well as for assessing the degree of functional compromise caused to the organ system involved. These tests should be selected on their relevance to the organ or site implicated in a focused clinical history and physical examination as well as in the original scan that detected the lesion. Though technically non-invasive, they can be expensive, disruptive if not easily and locally available and may still entail some risk if complex preparations such as bowel preparation are required.

It will not always be necessary to proceed to the second stage, that of invasive investigations (Box 26.2). The indications for this and the pattern of investigations chosen in stage 2 will depend on the findings from the non-invasive investigations of stage 1. Invasive or physiologically disruptive diagnostic procedures may include imaging guided biopsies, arteriography, barium enema, endoscopic procedures and associated biopsies or, less frequently, diagnostic laparoscopic or open surgery. All invasive investigations incur some risk, discomfort and expense. The patient must be fully informed about this and must be able to comply with the requirements of the investigation. Hence, a patient who cannot remain still may not be suitable for a percutaneous biopsy. A patient who suffers from claustrophobia may not be suitable for an MRI scan.

Asymptomatic gallstones

Calcification renders gallstones detectable on x-ray examinations. However, only about 10% of gallstones are calcified, so the detection rate on abdominal x-ray examinations is low. However, the sensitivity and specificity of ultrasound scanning for the detection of stones in the gallbladder (cholelithiasis) is high (over 90%) so the majority of incidentally detected gallstones are found on abdominal ultrasound scans. In this situation, further imaging is not usually required as in this situation ultrasound is the optimal imaging investigation in any case. If the stones are calcified and have been seen on CT scan, again no further investigation will be required. However, if stones are detected on CT but are not clearly seen as they are not calcified, an abdominal ultrasound will usually be required to be certain of the diagnosis. Other non-invasive tests such as liver function tests will not usually be required and invasive tests will similarly not be indicated for asymptomatic gallstones.

The question will arise: should a patient with asymptomatic gallstones be referred for surgical management? The answer is: usually not. Most truly asymptomatic gallbladder stones (asymptomatic cholelithiasis) remain asymptomatic. Approximately 10% of patients with asymptomatic cholelithiasis will develop symptoms attributable to their gallstones within 5 years of diagnosis, and approximately 20% by 20 years. The rate of symptom development is maximal in the early years after diagnosis. This then tapers off to 1–2% becoming symptomatic per year.

In general, the risks of surgery for asymptomatic gallstones outweigh the benefits, so prophylactic cholecystectomy is not usually recommended. Though the risk of gallbladder cancer is increased by gallbladder stones, it remains very low and should not be used as a justification for a patient with asymptomatic gallstones to undergo a prophylactic cholecystectomy. If previously asymptomatic gallstones do become symptomatic, cholecystectomy will usually be indicated. Biliary colic is the most common presenting symptom; only 10% of those developing symptoms will present with acute cholecystitis. Many mild cases of cholecystitis probably resolve quickly without a hospital admission. In such cases the stones are then diagnosed after the acute event has settled, allowing elective surgical referral and cholecystectomy. However, those cases of acute cholecystitis that present to a general practitioner or that result in hospital admission are best treated by immediate cholecystectomy.

Prophylactic cholecystectomy may be justifiable for gallstones larger than 2.5 cm; the risk of acute cholecystitis may be higher due to a higher risk of gallstone impaction in Hartmann’s pouch causing gallbladder outflow obstruction and acute cholecystitis. Prophylactic cholecystectomy may also be justified for diabetic patients with asymptomatic gallstones as acute cholecystitis may be more dangerous in these patients. Other situations where prophylactic cholecystectomy may be justified for asymptomatic gallstones include the very young, haemolytic disease, non-hepatic transplantation and porcelain gallbladder, where chronic infection associated with gallstones has resulted in calcification of the gallbladder wall (Figs 26.1 and 26.2). In all such cases, the clinical decision making should include appropriate specialist advice.

Figure 26.1 CT scan. Incidentally detected porcelain gallbladder (circled).

Figure 26.2 Plain abdominal x-ray. Porcelain gallbladder.

Incidentally detected gallbladder polyps

Polyps in the gallbladder are usually asymptomatic and are frequently detected by upper abdominal ultrasound carried out for other reasons. On ultrasound scanning, gallbladder polyps are differentiated from gallstones by their lack of mobility within the gallbladder (as they are attached to the gallbladder wall), and by the lack of acoustic shadowing that is a usual ultrasound scan feature of gallstones. Gallbladder polyps may be non-neoplastic or neoplastic. Non-neoplastic gallbladder polyps are made up of cholesterol and attached to the gallbladder epithelium so they do not move. Neoplastic (or adenomatous) gallbladder polyps arise from the gallbladder epithelium. Most gallbladder polyps are small (less than 1 cm) and most small gallbladder polyps are non-neoplastic. The risk that a polyp is an unsuspected gallbladder carcinoma is very low but increases with increasing polyp size. For this reason, polyps greater than 1 cm are generally removed by cholecystectomy. For polyps less than 1 cm the possibility of a small carcinoma is addressed by repeating the ultrasound in 3–6 months. If the lesion is stable the ultrasound is repeated at 12 months. A carcinoma would be expected to increase in size whereas small adenomatous polyps and cholesterol polyps are unlikely to change. Polyps larger than 1 cm or that enlarge should be regarded as suspicious, removed by cholecystectomy and submitted for histopathology.

Asymptomatic common bile duct dilatation

In normal patients younger than 60 years of age the upper limit of common bile duct size on ultrasound is 6 mm. This limit increases by 1 mm per decade after 60 years of age. The bile duct tends to be a little wider in women and also after cholecystectomy. Other causes of bile duct dilatation are listed in Box 26.3. The likelihood that incidentally detected common bile duct dilation is due to significant pathology and is revealing extrahepatic cholestasis is increased if the liver function tests, especially the serum bilirubin and alkaline phosphatase levels, are abnormal, so these are usually performed first. The likelihood of a malignant cause such as pancreatic head carcinoma or cholangiocarcinoma is increased if the tumour marker CA-19-9 is elevated, so this too should be checked in the phase of non-invasive investigations, especially if the serum bilirubin and serum alkaline phosphatase level are raised.

When a patient has presented with obstructive jaundice, endoscopic retrograde cholangiopancreatography (ERCP) for definitive diagnosis and relief of the jaundice will be a priority. However, when bile duct dilation has been an incidental finding on a scan one of the non-invasive modalities, usually CT cholangiography or MRCP, will be generally be carried out first to make sure that a subsequent ERCP with its attendant risks is really necessary. ERCP will not usually be indicated if the liver function tests are normal and no mass lesion, stone or stricture is seen on non-invasive imaging of the pancreas and biliary tree.

ERCP will usually be required if biliary imaging does reveal significant pathology. Though ERCP is invasive it has the advantage of allowing tissue sampling seeking a definitive diagnosis (brushings for cytology and biopsy for histopathology) and therapeutic interventions to treat cholestasis including clearance of bile duct stones, endoscopic sphincterotomy, dilatation of a benign stricture or placement of a biliary stent to achieve bile drainage past impacted bile duct stones, a malignant stricture or a tight benign stricture.

Asymptomatic choledocholithiasis

Asymptomatic choledocholithiasis may be detected incidentally on scans or through investigation of incidentally detected extrahepatic biliary dilation where the stones were not seen on the signal investigation. Common bile duct stones can be difficult to detect on abdominal ultrasound scanning even when the common bile duct is dilated as they may be obscured from detection on ultrasound scan by overlying gas in the duodenum, small bowel or colon.

Small stones may do no harm and may pass spontaneously. However, the risks associated with common bile duct stones should not be ignored. The incidence of complications of common bile duct stones is around 20% over 5 years, including serious problems such as obstructive jaundice, cholangitis and acute pancreatitis. Consequently, removal of stones in the common bile duct is generally recommended even if they are asymptomatic.

Where it is available, ERCP with endoscopic sphincterotomy and endoscopic stone extraction is the most common treatment for common bile duct stones that do not pass spontaneously (Fig 26.3). If ERCP is not available the duct is usually cleared by laparoscopic or open surgery. If the gallbladder is still present it is usually removed at the same operation. Thus, if ERCP is not readily available or, in patients not needing urgent clearance of the bile duct, a two-stage treatment (ERCP and subsequent surgical removal of the gallbladder) can on occasion be condensed into a single phase treatment by omitting the ERCP and utilising a single surgical procedure to remove the gallbladder and clear the bile duct, usually laparoscopically.

Figure 26.3 ERCP demonstrating stones in the bile duct. These had been difficult to see on ultrasound scan due to overlying bowel gas.

Choledochal cysts

Choledochal cysts are most commonly congenital and most commonly present with cholestasis during infancy. However, 20% present in adulthood, frequently as incidental scan findings in individuals with no biliary symptoms. Women are more commonly affected than men (80%; 4:1 female/male ratio). The development of some choledochal cysts may be explained by anomalous union of the common bile duct and pancreatic duct during embryogenesis. The resulting anatomy allows mixing of pancreatic juice and bile within the bile ducts. Exposure of the pancreatic exocrine proenzymes to bile activates the pancreatic digestive enzymes within the bile ducts, perhaps in turn leading to weakening and dilation of the duct and inducing epithelial changes predisposing to bile duct cancer (cholangiocarcinoma).

Choledochal cysts may occur anywhere in the biliary tree. They may be focal or diffuse, single or multiple. They are classified on the number of cysts present and on their position in the intra- or extrahepatic biliary tree (Table 26.1). Though not primarily caused by bile duct obstruction or by strictures, tumours or stones, all these problems may develop in association with them and may in turn lead to complications such as cholestasis (obstructive jaundice), infection in the biliary tree (cholangitis), impaired hepatic function (liver failure), hepatocellular loss and hepatic fibrosis (cirrhosis) and bile duct cancer (cholangiocarcinoma).

Table 26.1 Todani classification of choledochal cysts

ERCP = endoscopic retrograde cholangiopancreatography.

The discovery of intrahepatic or extrahepatic bile duct dilation consistent with choledochal cysts necessitates further investigation, initially by assessment of liver function and by MRCP or CT cholangiography. Masses associated with choledochal cysts anywhere in the biliary tree may be due to cholangiocarcinoma and should be assumed to be so until proven otherwise.

Extrahepatic choledochal cysts usually require excision of the extrahepatic ducts and reconstruction for biliary drainage with a choledochoenterostomy (anastomosis of the end of the remaining bile ducts to a loop of jejunum). Multiple intrahepatic cysts may not be amenable to surgery and are usually treated with endoscopic or percutaneous tubes (stents) in the bile ducts if biliary drainage is impaired. In such cases the cycle of chronic biliary obstruction and recurrent biliary sepsis may lead to liver failure and necessitate hepatic transplantation.

Focal pancreatitis