Clinical utility of vascular endothelial growth factor in diagnosing malignant pleural effusions

Figures & data

Figure 1.  A flow diagram for participants. The number of participants satisfying the criteria for inclusion that did or did not undergo the index tests and/or the reference standard is reported here. The reasons why participants failed to receive either test are also described.

Table I.  Key clinical and demographic characteristics of the study population [Means (SDs) except as noted].

Characteristic	Malignant PE group (n = 32)	Benign PE group (n = 49)
Age, years	57.7 (14.5)*	41.6 (18.1)
Sex, Number (% within group)
Male	17 (53.1)^†	37 (75.5)
Female	15 (46.9)	12 (24.5)
Main symptoms, Number (%)
Chest complaint	7 (21.9)	19 (38.8)
Chest distress	11 (34.4)	14 (28.6)
Fever	3 (9.4)	9 (18.4)
Cough	10 (31.3)	7 (14.3)
Other	1 (3.1)	0 (0)
Size of PE^a, Number (%)
Small	9 (28.1)	24 (49.0)
Moderate	13 (40.6)	19 (38.8)
Large	10 (31.3)	6 (12.2)
PF pH^b	7.05 (0.35)	7.13 (0.29)
PF glucose, mmol/L	5.81 (2.31)	5.29 (2.18)
PF protein, g/L	45.03 (18.68)	43.84 (14.63)
PF protein/serum protein	0.71 (0.30)	0.68 (0.22)
PF LDH, U/L	1374.3 (1288.1)	1112.7 (664.7)
PF LDH/serum LDH	7.24 (6.05)	6.93 (4.77)
PF cell count, cells/uL×10^−3	35.27 (103.64)	5.84 (9.46)
PF cytology^c, Number positive (%)	17 (53.1)*	0 (0)
Clinical outcome^d, Number (%)
Recovered	0 (0)*	33 (71.7)
Improved	0 (0)	7 (15.2)
Unchanged	0 (0)	2 (4.3)
Worse	2 (7.4)	2 (4.3)
Dead	25 (92.6)*	2 (4.3)

*p < 0.001 vs. Benign PE group; ^†p < 0.05 vs. Benign PE group.

^acriteria for size of PE: For free PE with pachynsis pleurae excluded, according to the upper level of dense shadow on chest x-ray films taken on erect position, “Small” was judged when the level was lower than the fourth front rib, “Large” decided when the level at or higher than the second front rib, and “Moderate” referred to those between the above two. For non-free PE, according to the amounts of fluid estimated by ultrasound examination, “Small” was defined as <0.5 L, “Large” as >2.0 L, and “Moderate” as between the above two. For bilateral PE, categorization was based on the side of a larger size. Data here are those when patients recruited; ^bdata concerning PF in this table were obtained from the first PF examination except as noted; ^cresults here include those of the initial and repeated examination of cytology if any; ^din comparison with the initial condition when recruited, the clinical outcome of each patient was categorized on the basis of the data of follow-up of one year and 10 months after recruitment, unless the definite outcome of “Recovered” or “Dead” had been obtained before. There were five malignant and three benign cases excluded here due to the indefinite outcome.

Abbreviations: LDH: lactate dehydrogenase, PE: pleural effusions, PF: pleural fluid.

Figure 2.  Standard curves and ROC curves in VEGF tests. A, (a) and (b) indicate the standard curves in VEGF tests on PF and serum, respectively; B, (c) and (d) show the ROC curves in VEGF tests on PF and serum, with the areas under the curves 0.686 (p = 0.005) and 0.834 (p < 0.001), respectively.

Figure 3.  Box-whisker plots representing the results of VEGF test on PF (a) and serum (b) in both groups. For PF VEGF level, the mean in malignant group was higher than that in benign group (1358±1493 pg/mL vs. 422±317 pg/mL, p = 0.001). As did for serum VEGF level (650±533 pg/mL vs. 137±189 pg/mL, p < 0.001).

Table II.  Results of VEGF test with the diagnostic cut-off points.

VEGF test strategy	Malignant PE group (n = 32)	Benign PE group (n = 49)
Test on PF, Number (% within group)
Positive (PF VEGF ≥ 959.25 pg/ml)	15 (47)*	2 (4)
Negative (PF VEGF < 959.25 pg/ml)	17 (53)	47 (96)
Test on serum, Number (% within group)
Positive (Serum VEGF ≥ 212.36 pg/ml)	22 (69)*	6 (12)
Negative (Serum VEGF < 212.36 pg/ml)	10 (31)	43 (88)

*p < 0.001 vs. Benign PE group.

Abbreviations: PE: pleural effusions, PF: pleural fluid, VEGF: vascular endothelial growth factor.

Table III.  Sensitivities and specificities of different VEGF test strategies [Rates of sample (95% confidence intervals)].

Test Strategy	Sensitivity, %	Specificity, %
PF VEGF^a (A)	47 (29–65)	96 (86–99)
Serum VEGF^b (B)	69 (50–84)	88 (75–95)
Cascade connection of Test A and B (C)	34 (19–53)	98 (89–100)
Parallel operation of Test A and B (D)	81 (64–93)	86 (73–94)

^apositive and indicative of malignancy if greater than or equal to 959.25 pg/ml; ^bpositive and indicative of malignancy if greater than or equal to 212.36 pg/ml.

Abbreviations: PF: pleural fluid, VEGF: vascular endothelial growth factor.