Role of endoscopic ultrasound and cyst fluid tumor markers in diagnosis of pancreatic cystic lesions

Table 1 Descriptive data of included patients

Gender	Number	Percent (%)
Male	31	40.80%
Female	45	59.20%
Total	76	100%

Table 2 Endoscopic ultrasound findings of studied patients

EUS finding		Number	Percent (%)
Loculation	Unilocular	40	0.526
	Multilocular	36	0.474
Mural nodules	No	52	0.684
	Yes	24	0.316
Wall	Thin Wall	59	0.776
	Thick Wall	17	0.224
Content	Clear	60	0.789
	Turbid	16	0.211
Calcification	No	70	0.921
	Yes	6	0.079
LNs	No	63	0.829
	Yes	13	0.171
Pancreatic duct dilation	No	66	0.868
	Yes	10	0.132

EUS: Endoscopic ultrasound.

Table 3 Final diagnosis

Final diagnosis	Number	Percent (%)
Pancreatic pseudocyst	30	39.5
Pancreatic pseudocyst with WOPN	1	1.3
Serous cystadenoma	13	17.1
Mucinous cystadenoma	11	14.5
IPMN (high grade dysplasia)	10	13.2
IPMN (low grade dysplasia)	6	7.9
Pancreatic adenocarcinoma	4	5.3
Cystic lymphangioma	1	1.3
Total	76	100

IPMN: Intraductal papillary mucinous neoplasm; WOPN: Walled-off pancreatic necrosis.

Table 4 Mucin stain in detecting mucinous from non-mucinous pancreatic cystic lesions

Statistic	Value	95%CI
Sensitivity	100%	86.77% to 100%
Specificity	94%	83.45% to 98.75%
Positive likelihood ratio	16.67	5.56 to 49.93
Negative likelihood ratio	0
Disease prevalence	34.21%	23.71% to 45.99%
Positive predictive value	89.66%	74.31% to 96.29%
Negative predictive value	100%
Accuracy	96.05%	88.89% to 99.18%

Table 5 Mucin stain in detecting benign from malignant pancreatic cystic lesions

Statistic	Value	95%CI
Sensitivity	87.10%	70.17% to 96.37%
Specificity	95.56%	84.85% to 99.46%
Positive likelihood ratio	19.60	5.02 to 76.47
Negative likelihood ratio	0.14	0.05 to 0.34
Disease prevalence	40.79%	29.65% to 52.67%
Positive predictive value	93.10%	77.58% to 98.14%
Negative predictive value	91.49%	81.12% to 96.41%
Accuracy	92.11%	83.60% to 97.05%

Table 6 Cyst fluid carcinoembryonic antigen, serine protease inhibitor Kazal-type 1, and glucose level in studied patients

Biochemical test	Median (IQR)	Range
CEA (ng/ml)	90 (8.78- 1560)	(5-100000)
SPINK1 (ng/ml)	0.56 (0.35-0.97)	(0.1-2.32)
Glucose (mg/dl)	50 (10-84)	(2-171)

IQR: Interquartile range.

Table 7 Cystic fluid analysis of malignant/potentially and benign cysts

Variable	Benign group(n = 45)	Malignant group(n = 31)	P value
Mucin stain positivity	2 (4.4%)	27 (87.1%)	< 0.0001
Number (%)
Glucose (mg/dl)	21.5 (4-45)	68.5 (47-87)	0.0001
median (IQR)
IL1b (pg/mL)	0.37 (0.58)	0.34 (0.45)	0.845
(median, IQR)
CA 72-4 (U/mL)	6.36 (9.7)	7.4 (7.6)	0.323
(median, IQR)
VEGF-A (pg/ml)	707.8 (1056)	736.9 (2262)	0.866
(median, IQR)
VEGFR2 (pg/ml)	2.5 (5.3)	1.3 (3)	0.281
(median, IQR)
SPINK1 (ng/ml)	0.91 (0.41-1.45)	0.47 (0.3-0.72)	0.001
median (IQR)
PGE2 (pg/ml)	307.2 (131)	409.7 (176)	0.121
(median, IQR)
CF amylase (U/L)	130.5 (353)	3060 (5191)	0.034
(median, IQR)
CF CEA (ng/ml)	6.4 (234)	15.8 (2532)	0.004
(median, IQR)
CEA (> 192 ng/mL)	15	5	0.001

CEA: Carcinoembryonic antigen; CF: Cyst fluid; IQR: Interquartile range; VEGFR2: Vascular endothelial growth factor receptor 2; SPINK1: Serine protease inhibitor Kazal-type 1.

Table 8 Value of different variables in predicting malignancy

Variable	Criterion	Specificity	Sensitivity	PPV	NPV	P value	AUC
Age	> 35	0.244	1	0.4745	1	0.605	0.534
Mucin stain		0.9556	0.871	0.931	0.9149	< 0.001	0.913
Glucose (mg/dL)	≤ 42	0.7353	0.8478				0.76
IL1b (pg/mL)	< 1.13	0.209	0.9	0.4363	0.7464	0.761	0.521
CA 72-4 (U/mL)	> 4.3138	0.467	0.677	0.4657	0.678	0.32	0.567
VEGF-A (pg/mL)	> 1221.7	0.844	0.29	0.561	0.634	0.87	0.511
VEGFR2 (pg/ml)	> 6.601	0.933	0.29	0.7482	0.657	0.301	0.573
SPINK1 (μg/L)	≥ 0.58	0.6533	0.7059	0.708	0.623		0.72
PGE2 (pg/ml)	> 311.77	0.556	0.8	0.5529	0.802	0.102	0.683
CF amylase (U/L)	> 270	0.71	0.711	0.629	0.781	0.028	0.644
CF CEA (ng/ml)	> 8	0.742	0.689	0.622	0.795	< 0.001	0.761

CA: Cancer antigen; CF: Cyst fluid; VEGFR2: Vascular endothelial growth factor receptor 2; PPV: Positive predictive value; NPV: Negative predictive value.

Table 9 Logistic regression analysis for predictors of malignancy in cystic pancreatic lesions

Variable	Univariate analysis		Multivariate analysis
	OR (95%CI)	P value	OR (95%CI)	P value
Age	1.06 (0.97-1.06)	0.4312
Mural nodules	6.6 (2.3- 19.3)	0.0006	5.7 (1.37-24.6)	0.0172
Wall thickness	1.39 (0.47-4.124)	0.5514
LNs	11.82 (2.4-58.4)	0.0024	0.14 (0.006-3.3)	0.2219
Content	0.59 (0.18-1.923)	0.3851
Loculation	1.1 (0.43-2.68)	0.8826
Calcification	1.5 (0.28-7.97)	0.6342
Shortest Diameter	0.965 (0.94-0.99)	0.0189	1.06 (0.92-1.22)	0.4044
Longest Diameter	0.971(0.95-0.99)	0.0112	0.913 (0.81- 1.03)	0.1326
Mucin Stain	145 (24.8-847.2)	< 0.0001	82.4 (12.1-561)	< 0.0001
Glucose	0.97 (0.96-0.99)	> 0.001	0.99 (0.97-1.01)	0.48
IL1b (pg/mL)	0.91 (0.702-1.18)	0.496
CA 72-4	1.02 (0.98-1.053)	0.3017
VEGF-A	1.0001(0.99-1.0005)	0.5782
VEGFR2	1.14 (0.99-1.318)	0.0782
SPINK1	9.09 (2.62-31.59)	0.001	23.65 (3.10-180.62)	0.002
PGE2 (pg/mL)	1.01 (0.999-1.02)	0.0798
CF Amylase	1 (1-1)	0.8593
CF CEA	1.0003 (1.0001-1.0005)	0.0152	1.0001 (0.99-1.0006)	0.5978
CEA > 192 (ng/mL)	6.47 (2.05-20.42)	0.001	14.12 (2.39-83.22)	0.003

OR: Odds ratio; CI: Confidence interval; LNs: Lymph-nodes; CF: Cyst fluid; CA: Cancer antigen; CEA: Carcinoembryonic antigen; SPINK1: Serine protease inhibitor Kazal-type 1; IL1-β: Interleukin 1 beta; CA 72-4: Human cancer antigen 72-4; VEGF-A: Vascular endothelial growth factor A; VEGFR2: Vascular endothelial growth factor receptor 2, PGE2: Prostaglandin E2.

Table 10 Performance of EUS diagnosis for malignant/premalignant and benign cysts

Statistic	Value	95%CI
Sensitivity	0.6667	40.99% to 86.66%
Specificity	0.6923	48.21% to 85.67%
Positive predictive value	0.6	43.60% to 74.42%
Negative predictive value	0.75	59.79% to 85.82%
Accuracy	0.6818	52.42% to 81.39%

Table 11 Follow-up data of studied patients

Follow-up	Stationary	Regressive	No-recurrence	Progressive	Died
Pancreatic pseudocyst (n = 30)	27 (35.5%)	3 (3.9%)	0	0	0
Pancreatic pseudocyst with WOPN (n = 1)	0	0	1 (1.3%)	0	0
Serous cystadenoma (n = 13)	12 (15.7%)	0	1 (1.3%)	0	0
Mucinous cystadenoma (n = 10)	9	0	1 (1.3%)	0	0
Mucinous cystadenocarcinoma (n = 1)	0	0	0	1	0
IPMN (high grade dysplasia) (n = 10)	3	0	7	0	0
IPMN (low grade dysplasia) (n = 6)	6	0	0	0	0
Pancreatic adenocarcinoma (n = 4)	0	0	2 (2.6%)	0	2 (2.6%)
Cystic lymphangioma (n = 1)	1 (1.3%)	0	0	0	0
Total (n = 76)	40 (52.6%)	3 (3.9%)	5 (6.5%)	0	2 (2.6%)

Table 12 Intervention required for studied patients

Intervention required	No	Surgery	Pig-tail drainage	Cysto-gastrostomy
Pancreatic pseudocyst (n = 30)	26 (34.2%)	1 (1.3%)	2 (2.6%)	1 (1.3%)
Pancreatic pseudocyst with WOPN (n = 1)	0	1 (1.3%)	0	0
Serous cystadenoma (n = 13)	12 (15.8%)	1 (1.3%)	0	0
Mucinous cystadenoma (n = 10)	9 (11.7%)	1 (1.3%)	0	0
Mucinous cystadenocarcinoma (n = 1)	1 (1.3%)	0	0	0
IPMN (high grade dysplasia) (n = 10)	1 (1.3%)	9 (11.8%)	0	0
IPMN (low grade dysplasia) (n = 6)	6 (7.9%)	0	0	0
Pancreatic adenocarcinoma (n = 4)	0	4 (5.2%)	0	0
Cystic lymphangioma (n = 1)	1 (1.3%)	0	0	0
Total (n = 76)	56 (73.7%)	17 (22.4%)	2 (2.6%)	1 (1.3%)