El francés en el grado noveno: construcción de la unidad piloto

Malignant cystic neoplasm

The prevalence of malignant cystic neoplasm in the patient cohort was 1.5% (95% CI 0.5% to 2.5%). The small number of patients diagnosed with malignant cystic neoplasm (Table 35) means that statistical tests comparing the diagnostic tests have low power to detect small or moderate effects.

Both MDCT and PET/CT had a sensitivity of 75.0% (95% CI 45.0% to 99.9%). The specificity of PET/CT was higher than that of MDCT [96.1% (95% CI 94.5% to 97.8%) vs. 92.8% (95% CI 90.6% to 95.0%)]. The 3.6% (95% CI 1.8% to 5.4%) improvement in specificity between tests was statistically significant (p<0.001) (Table 36). The very small number of cases of malignant cystic neoplasm meant that the significant difference in specificity did not translate into a significant difference in either PPV or NPV.

Cholangiocarcinoma

The prevalence of cholangiocarcinoma in the patient cohort was 8.0% (95% CI 5.7% to 10.3%). The small number of patients diagnosed with cholangiocarcinoma (Table 37) means that statistical tests comparing the diagnostic tests have low power to detect small or moderate effects.

Both MDCT and PET/CT had a relatively high specificity (97.8% and 98.8%, respectively) but low sensitivity (25% in each case). There were no significant differences in either sensitivity or specificity (Table 38). TABLE 34 Effect of eligibility criterion 3 (serum CA19.9>37 kU/l) on sensitivity and specificity

Measure MDCT PET/CT Relative Criterion 3 met Criterion 3 not met Criterion 3 met Criterion 3 not met Criterion 3 met Criterion 3 not met Sensitivity (95% CI) (%) 89.7 (84.4 to 93.3) 85.7 (76.0 to 91.9) 92.9 (88.2 to 95.9) 92.2 (83.7 to 96.5) 1.04 (0.99 to 1.09) 1.08 (1.01 to 1.15) p₌0.362 p₌0.580 p₌0.505 Specificity (95% CI) (%) 71.5 (65.6 to 76.7) 65.0 (49.2 to 78.1) 76.3 (70.6 to 81.2) 72.5 (56.8 to 84.1) 1.07 (0.94 to 1.22) 1.12 (0.95 to 1.31) p₌0.404 p₌0.704 p₌0.730

Prevalence of D4-positive diagnosis of PDAC by criterion 3 status: criterion met 65.8%, criterion not met 42.5%;p<0.0001.

TABLE 35 Multidetector computed tomography and PET/CT diagnosis against malignant cystic neoplasm status Diagnosis Malignant cystic neoplasm No malignant cystic neoplasm

MDCT positive 6 39

MDCT negative 2 503

PET/CT positive 6 21

Similarly, although the improvement in sensitivity (for cholangiocarcinoma) for the PET/CT scan translated into an improvement in PPV, the effect was not significant. Although a positive diagnosis of cholangiocarcinoma on PET/CT or MDCT greatly increases the odds of a patient having cholangiocarcinoma, there was still considerable uncertainty about the diagnosis (PPV 50% for MDCT and 65% for PET/CT). Moreover, the NPVs were very close to the original prevalence reflecting that the tests have poor negative likelihood ratios (0.77 and 0.76 for MDCT and PET/CT, respectively).

Neuroendocrine tumours

The prevalence of neuroendocrine tumours in the patient cohort was 4.9% (95% CI 3.1% to 6.7%). The small number of patients diagnosed with neuroendocrine tumour (Table 39) means that statistical tests comparing the diagnostic tests have low power to detect small or moderate effects.

TABLE 37 Multidetector computed tomography and PET/CT diagnosis against cholangiocarcinoma status

Diagnosis Cholangiocarcinoma No cholangiocarcinoma

MDCT positive 11 11

MDCT negative 33 495

PET/CT positive 11 6

PET/CT negative 33 500

TABLE 38 Sensitivity, specificity, PPV and NPV for MDCT and PET/CT in relation to diagnosis of cholangiocarcinoma

Measure MDCT PET/CT Relative p-value

Sensitivity (95% CI) (%) 25.0 (12.2 to 37.8) 25.0 (12.2 to 37.8) 1.00 (0.64 to 1.36) 1.000 Specificity (95% CI) (%) 97.8 (96.6 to 99.1) 98.8 (97.8 to 99.8) 1.01 (1.00 to 1.02) 0.094 PPV (95% CI) (%) 50.0 (29.1 to 70.9) 64.7 (42.0 to 87.4) 1.29 (0.86 to 1.94) 0.214 NPV (95% CI) (%) 93.8 (91.7 to 95.8) 93.8 (91.8 to 95.9) 1.00 (0.98 to 1.02) 0.954

TABLE 39 Multidetector computed tomography and PET/CT diagnosis against neuroendocrine tumour status Diagnosis Neuroendocrine tumour No neuroendocrine tumour

MDCT positive 12 3

MDCT negative 15 520

PET/CT positive 12 7

PET/CT negative 15 516

TABLE 36 Sensitivity, specificity, PPV and NPV for MDCT and PET/CT in relation to diagnosis of malignant cystic neoplasm

Measure MDCT PET/CT Relative p-value

Sensitivity (95% CI) (%) 75.0 (45.0 to 99.9) 75.0 (45.0 to 99.9) 1.00 (0.54 to 1.46) 1.0 Specificity (95% CI) (%) 92.8 (90.6 to 95.0) 96.1 (94.5 to 97.8) 1.04 (1.02 to 1.05) <0.001 PPV (95% CI) (%) 13.3 (3.4 to 23.3) 22.2 (6.5 to 37.9) 1.67 (0.97 to 2.87) 0.066 NPV (95% CI) (%) 99.6 (99.1 to 99.9) 99.6 (99.1 to 99.9) 1.00 (0.99 to 1.01) 0.967

Both MDCT and PET/CT had a very high specificity (99.4% and 98.7%, respectively) but low sensitivity (44.4% in both cases). The relative specificity and relative sensitivity of MDCT and PET/CT were not significantly different (Table 40).

The slightly lower specificity for PET/CT meant that the PPV was estimated to be lower for PET/CT.

However, the difference was not statistically significant. Similarly, the NPV was slightly lower but again the difference was not significant.

Periampullary carcinoma

The prevalence of periampullary carcinoma in the patient cohort was 6.9% (95% CI 4.8% to 9.0%). The small number of patients diagnosed with periampullary carcinoma (Table 41) means that statistical tests comparing the diagnostic tests have low power to detect small or moderate effects.

Both MDCT and PET/CT had a relatively high specificity (95.9% and 97.2%, respectively) but relatively low sensitivity (71.1% and 65.8%, respectively) (Table 42). The relative specificity of PET/CT compared with MDCT was statistically significant (p=0.034) but the practical improvements were outweighed by the observed, although non-significant, reduction in sensitivity.

TABLE 40 Sensitivity, specificity, PPV and NPV for MDCT and PET/CT in relation to diagnosis of neuroendocrine tumour

Measure MDCT PET/CT Relative p-value

Sensitivity (95% CI) (%) 44.4 (25.7 to 63.2) 44.4 (25.7 to 63.2) 1.00 (0.67 to 1.33) 1.000 Specificity (95% CI) (%) 99.4 (98.8 to 99.9) 98.7 (97.7 to 99.6) 0.99 (0.98 to 1.00) 0.159 PPV (95% CI) (%) 80.0 (59.8 to 99.9) 63.2 (41.5 to 84.8) 0.79 (0.55 to 1.13) 0.191 NPV (95% CI) (%) 97.2 (95.8 to 98.6) 97.2 (95.8 to 98.6) 1.00 (0.98 to 1.01) 0.977

TABLE 41 Multidetector computed tomography and PET/CT diagnosis against periampullary carcinoma status Diagnosis Periampullary carcinoma No periampullary carcinoma

MDCT positive 27 21

MDCT negative 11 491

PET/CT positive 25 14

PET/CT negative 13 498

TABLE 42 Sensitivity, specificity, PPV and NPV for MDCT and PET/CT in relation to diagnosis of periampullary carcinoma

Measure MDCT PET/CT Relative p-value

Sensitivity (95% CI) (%) 71.1 (56.6 to 85.5) 65.8 (50.7 to 80.9) 0.92 (0.74 to 1.11) 0.432 Specificity (95% CI) (%) 95.9 (94.2 to 97.6) 97.2 (95.9 to 98.7) 1.01 (1.00 to 1.03) 0.034 PPV (95% CI) (%) 56.3 (42.2 to 70.3) 64.1 (49.0 to 79.2) 1.14 (0.90 to 1.44) 0.278 NPV (95% CI) (%) 97.8 (96.5 to 99.1) 97.5 (96.1 to 98.8) 1.00 (0.98 to 1.01) 0.633

Although PET/CT gave an improved PPV, the relative PPV was not significantly different from 1. Moreover, the estimated NPV was worse for PET/CT than for MDCT, although this differences was also non-significant.

Malignant compared with benign disease

The prevalence of any malignant disease among the patient population was 69.8% (95% CI 66.0% to 73.7%).Table 43provides the 2 × 2 table for MDCT and PET/CT diagnosis by malignant or benign disease status (D4).

Both MDCT and PET/CT scans had high sensitivity with respect to detecting any malignancy (97.4% and 97.7%, respectively) but there was no evidence that PET/CT had better sensitivity (p=0.763) (Table 44). In contrast, the specificity of PET/CT was considerably higher than that for MDCT (68.7% vs. 47.0%, relative sensitivity 1.46;p<0.0001). The improvement in specificity also corresponded with a statistically significant improvement in PPV, increasing from 80.9% for MDCT to 87.8% for PET/CT (p=0.0002). The NPV also improved but by a non-significant margin (relative NPV 1.05;p=0.24).

Incremental diagnostic benefit for malignancy versus benign

Using the Knottnerus method, estimates of the incremental likelihood ratios corresponding to a positive or negative PET/CT diagnosis with respect to whether the tumour was malignant or benign were obtained. In each case, the results of the PET/CT scan had a statistically significant impact on the odds of malignancy. The results suggest particular benefits of administering PET/CT after a positive MDCT scan. A positive PET/CT assessment following a positive MDCT assessment was estimated to increase the odds of malignancy by a further 88.7% (95% CI 55.4% to 134.8%) whereas a negative PET/CT assessment following a positive MDCT assessment reduced the odds of malignancy by 97.2% (95% CI 94.4% to 99.5%), meaning that malignancy is very unlikely for these patients (NPV 89.4%). A positive PET/CT assessment following a negative MDCT assessment increased the odds of malignancy by 680% (95% CI 106% to 2735%). However, there was still considerable uncertainty in the diagnosis of these patients (PPV 50.0%). A negative PET/CT assessment following a negative MDCT assessment decreased the odds of malignancy by 60.6% (95% CI 25.6% to 90.3%) and these patients were very unlikely to have a malignancy (NPV 94.7%) (Figure 6).

TABLE 43 Multidetector computed tomography and PET/CT diagnosis against malignancy status

Diagnosis Malignant Benign

MDCT positive 374 88

MDCT negative 10 78

PET/CT positive 375 52

PET/CT negative 9 114

TABLE 44 Sensitivity, Specificity, PPV and NPV of MDT-CT and PET/CT in relation to diagnosis of malignant disease

Measure MDCT PET/CT Relative p-value

Sensitivity (95% CI) (%) 97.4 (95.8 to 99.0) 97.7 (96.1 to 99.2) 1.00 (0.99 to 1.02) 0.763 Specificity (95% CI) (%) 47.0 (39.4 to 54.6) 68.7 (61.6 to 75.7) 1.46 (1.32 to 1.61) <0.0001 PPV (95% CI) (%) 80.9 (77.3 to 84.5) 87.8 (84.7 to 90.9) 1.08 (1.04 to 1.13) 0.0002 NPV (95% CI) (%) 88.6 (82.0 to 95.2) 92.7 (88.1 to 97.3) 1.05 (0.97 to 1.13) 0.240