predictors of malignancy: RESULTS

Biochemistry: Mean serum values for ALT, AST, AP, biliru- bin and BA were significantly higher in the malignant stric­ture group than in the benign stricture group (Figure 1). The most striking difference between the two groups was in the serum bilirubin levels – 317.8±43 pmol/L (SEM) versus 22.1±5 pmol/L (P<0.001) for the malignant versus the be­nign group.

To examine the clinical utility of these biochemical dif­ferences, ROC curves were constructed for each variable. Threshold values and likelihood ratios are provided in Ta­ble 2.

Ultrasound: Intrahepatic duct dilation, defined by a visible lumen within the intrahepatic ducts, was detected in 19 of the 29 strictures (66%). This finding was observed in 93% of malignant strictures versus 36% of benign strictures (P=0.002, Fisher’s exact test). Common hepatic duct dila­tion tended to be greater in malignant than in benign stric­tures (13.5 versus 9.6 mm; P=0.11, two-tailed t test). Where duct dilation was found, the stricture location could be deter­mined on the ultrasound. Additional helpful ultrasono- graphic findings were frequently found in the malignant subgroup and included a pancreatic mass in nine of 15, of whom three patients also showed evidence of metastases to the liver or regional lymph nodes. Four patients were shown to have a biliary ductal mass, of whom two had evidence of nodal metastases. In one patient, only liver metastases were demonstrated. Only one patient with a malignant stricture had none of the above abnormalities. Ultrasound was, there­fore, highly sensitive (93%) in the detection of malignant ob­struction by visualizing the actual mass or metastases. Conversely, in benign disease, ultrasound was insensitive in diagnosing biliary obstruction with more than half of the cases lacking both intrahepatic and extrahepatic biliary dila­tion.

Disida scan: Iminodiacetic acid imaging of the hepatobiliary tree was obtained in 26 of the 29 patients. Three patients were not studied due to the need for urgent biliary decom­pression. All 12 Disida scans obtained in patients with malig­nant strictures were abnormal; two showed hepatocellular dysfunction alone (poor uptake of radionuclide from blood) and 10 showed evidence of cholestasis or obstruction. Of the 14 Disida scans from patients with benign strictures, seven were normal or minimally abnormal (not diagnostic), six showed evidence of cholestasis or obstruction and one showed hepatocellular dysfunction. The overall sensitivity of Disida for the diagnosis of obstruction was 50%.

TABLE 2 Threshold values and likelihood ratios for malignancy

Parameter threshold

Estimated threshold

Threshold TPR

Threshold FPR

Likelihood ratio

Bilirubin

75 Umol/L

0.946

0.001

100

ALT

100 U/L

0.79

0.14

5.6

Serum bile acids

150 Umol/L

0.83

0.17

4.9

Alkaline

phosphatase

400 U/L

0.86

0.20

4.3

Stricture length at ERCP

14 mm

0.78

0.23

3.4

AST

150 IU/L

0.57

0.21

2.7

Gamma GT

450 IU/L

0.74

0.31

2.38

The differentiation between intrahepatic cholestasis and extrahepatic obstruction was generally not possible, except in cases with partial filling of a dilated proximal duct or where regional delay of hepatic excretion suggested partial obstruction of the right or left hepatic duct. The specificity of Disida for the diagnosis of bile duct obstruction is, there­fore, poor but could not be calculated from this study. De- convolutional analysis for calculation of the hepatic extraction fraction (a measure of hepatocellular function) and biliary excretion half-life yielded inconsistent results and failed to improve the diagnostic accuracy of Disida scan­ning (data not shown).

TABLE 3 Biliary stricture location

Location

Patients (n)

Malignant:benign

Intrahepatic

4

0:4

CHD/hilar

5

3:2

CBD

17

12:5

Papillary

3

0:3

Cholangiography: A cholangiogram was obtained in all 29 patients; 25 had successful ERCPs, four had PTCs due to sur­gically altered anatomy or failed ERCP. Stricture location and subclassification according to benign or malignant cause is summarized in Table 3. Strictures involving the common bile duct were more likely to be malignant than those of the papilla or intrahepatic ducts. A classic double duct sign (abrupt cutoff of both the pancreatic and bile ducts) was seen in only three of 10 patients with cancer of the pancreas who had their cholangiogram by ERCP. Of the remaining pa­tients, only a single patient had a double duct sign due to be­nign strictures involving both ducts.
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There was a significant difference in stricture length between the malignant and benign groups – 30.3 versus 9.2 mm (P=0.001). Threshold analysis using ROC curves showed that a stricture length of 14 mm or greater was predictive of malignancy (sensitivity 98%, specificity 77%). Cholangio- graphic characterization of each stricture as smooth (‘radi- ologically benign’) or irregular (‘radiologically malignant’) was possible in 26 cases. There was a similar number of smooth (eight of 13) and irregular (five of 13) type strictures in the malignant group; 10 of 13 benign strictures were smooth. Stricture width was difficult to measure accurately and did not discriminate malignant from benign strictures. Furthermore, a ratio of stricture width to proximal dilated duct width (as a cholangiographic measure of obstruction) was not helpful (data not shown).