Cholangiocarcinoma, n=92

Sensitivity (95% CI) Specificity (95% CI) PPV (95% CI) NPV (95% CI)

Brush, n=85 44.7% 89.4% 77.3% 66.7%

(28.6% - 61.7%) (76.9% - 96.5%) (54.6% - 92.2%) (53.7% - 78.0%)

FISH, n= 84 45.9% 95.7% 89.5% 69.2%

(29.5% -63.1%) (85.5% -99.5%) (66.9% - 98.7%) (56.6% - 80.1%)

Transpapillary Biopsy, 44.1% 97.3% 93.8% 65.5%

n=71
(27.2% - 62.1%) (85.8% - 99.9%) (69.8% - 99.8%) (51.4% - 77.8%)

Spybite biopsy, n=64 43.3% 97.1% 92.9% 66.0%

(25.5% - 62.6%) (84.7% - 99.9%) (66.1% - 99.8%) (51.2% - 78.8%)

Brush + FISH, n=84 56.8% 89.4% 80.8% 72.4%

(39.5% - 72.9%) (76.9% - 96.5%) (60.6% - 93.4%) (59.1% - 83.3%)

Brush + FISH + Spybite 71.4% 86.7% 83.3% 76.5%

biopsy, n=58
(51.3% - 86.8%) (69.3% - 96.2%) (62.6% - 95.3%) (58.8% - 89.3%)

Brush + FISH 64.5% 84.8% 80.0% 71.8%

+Transpapillary
biopsy, n=64 (45.4% - 80.8%) (68.1% - 94.9%) (59.3% - 93.2%) (55.1% - 85.0%)

Brush+ FISH+ Spybite 69.2% 82.6% 81.8% 70.4%

biopsy + transpapillary
biopsy, n=49 (48.2% - 85.7%) (61.2% - 95.0%) (59.7% - 94.8%) (49.8% - 86.2%)

Cholangiocarcinoma in patients with PSC, n=36

Brush, n=35 50.0% 89.5% 80.0% 68.0%

(24.7% - 75.3%) (66.9% - 98.7% (44.4% - 97.5%) (46.5% - 85.1%)

FISH, n=35 56.2% 100.0% 100.0% 73.1%

(29.9% - 80.2%) (82.4% -100.0%) (66.4% - 100.0%) (52.2% - 88.4%)

Transpapillary biopsy, 38.5% 100.0% 100.0% 60.0%

n= 25
(13.9% - 68.4%) (73.5% - 100.0%) (47.8% -100.0%) (36.1% - 80.9%)

Spybite biopsy, n=23 36.4% 91.7% 80.0% 61.1%

(10.9% - 69.2%) (61.5% - 99.8%) (28.4% - 99.5%) (35.7% - 82.7%)

Brush + FISH, n=35 62.5% 89.5% 83.3% 73.9%

(35.4% - 84.8%) (66.9% - 98.7%) (51.6% - 97.9%) (51.6% - 89.8%)

Brush +FISH + Spybite 63.6% 83.3% 77.8% 71.4%

biopsy, n=23
(30.8% - 89.1%) (51.6% - 97.9%) (40.0% -97.2%) (41.9% - 91.6%)

Brush + FISH + 58.3% 83.3% 77.8% 63.6%

transpapillary biopsy,
n=24 (27.7% - 84.8%) (51.6% -97.9%) (40.0% - 97.2%) (30.8% - 89.1% )

Brush+ FISH+ Spybite 60.0% 77.8% 75.0% 63.6%

biopsy + transpapillary
biopsy, n=19 (26.2% - 87.8%) (40.0% - 97.2%) (34.9% - 96.8%) (30.8% - 89.1%)
Tests comparison:

We compared the performance of different test combinations using McNemar exact test and using brush cytology as the reference

diagnostic test.

Sensitivity comparison between the combined tests using brush cytology as the
reference
Test P value
Brush Reference
Brush + FISH 0.12
Brush + FISH + Spybite biopsy 0.03
Brush + FISH +Transpapillary biopsy 0.01
Brush+ FISH+ Spybite biopsy + 0.03
transpapillary biopsy
 Tests performance in patients who had all the diagnostic tests performed, n=49

Sensitivity (95% CI) Specificity (95% CI) PPV (95% CI) NPV (95% CI)

Brush, n=49 46.2% 82.6% 75.0% 57.6%

(26.6% - 66.6%) (61.2% - 95.0%) (47.6% -92.7%) (39.2% - 74.5%)

FISH, n= 49 46.2% 91.3% 85.7% 60.0%

(26.6% - 66.6%) (72.0% - 98.9%) (57.2% - 98.2%) (42.1% - 76.1%)

Transpapillary Biopsy, 38.5% 95.7% 90.9% 57.9%

n=49
(20.2% - 59.4%) (78.1% - 99.9%) 58.7% - 99.8% (40.8% - 73.7%)

Spybite biopsy, n=49 42.3% 95.7% 91.7% 59.5%

(23.4% - 63.1%) (78.1% - 99.9%) (61.5% - 99.8%) (42.1% -75.2%)

Brush + FISH, n=49 57.7% 82.6% 78.9% 63.3%

(36.9% - 76.6%) (61.2% - 95.0%) (54.4% - 93.9%) (43.9% - 80.1%)

Brush + FISH + Spybite 69.2% 82.6% 81.8% 70.4%

biopsy, n=49
(48.2% - 85.7%) (61.2% - 95.0%) (59.7% - 94.8%) (49.8% - 86.2%)

Brush + FISH 69.2% 82.6% 81.8% 70.4%

+Transpapillary
biopsy, n=49 (48.2% - 85.7%) (61.2% - 95.0%) (59.7% - 94.8%) (49.8% - 86.2%)

Brush+ FISH+ Spybite 69.2% 82.6% 81.8% 70.4%

biopsy + transpapillary
biopsy, n=49 (48.2% - 85.7%) (61.2% - 95.0%) (59.7% - 94.8%) (49.8% - 86.2%)
Patients who were negative for cholangiocarcinoma had a median follow up of 371 days (IQR: 194 – 1618).