Carbohydrate antigen 19-9 for differential diagnosis of pancreatic carcinoma and chronic pancreatitis

Table 1 Summary of carbohydrate antigen 19-9 assay methods, results, and overall methodological quality of included studies

Ref.	Number of patient	Assay method	Cut-off for elevated CA19-9 (U/mL)	Assay results				Quality score
				TP	FP	FN	TN	STARD	QUADAS
Wang et al[21], 1986	58	RIA	37	20	0	4	34	15	10
Safi et al[22], 1987	191	RIA	37	80	28	7	76	16	10
Sakamoto et al[23], 1987	57	RIA	37	26	1	4	26	18	12
Friess et al[24], 1993	154	ELISA	37	53	14	6	81	17	11
Röthlin et al[25], 1993	97	RIA	37	54	8	14	21	17	12
Haglund et al[26], 1994	199	RIA	37	148	3	31	17	16	11
Kuno et al[27], 1994	117	RIA	37	41	10	6	60	19	13
Pasquali et al[28], 1994	103	RIA	37	47	2	11	43	12	9
Satake et al[29], 1994	941	RIA	37	454	56	118	244	19	13
Hámori et al[30], 1997	94	RIA	37	48	4	14	28	11	7
Safi et al[31], 1997	647	RIA	37	296	48	51	252	18	12
Hayakawa et al[32], 1999	76	RIA	37	21	14	6	35	16	11
Kim et al[33], 1999	160	ELISA	37	69	9	21	61	19	13
Manes et al[34], 1999	58	RIA	37	30	3	4	21	17	11
Slesak et al[35], 2000	122	LIA	37	32	14	14	60	18	12
Maire et al[36], 2002	78	ELISA	37	43	4	4	27	17	11
Akashi et al[37], 2003	46	RIA	37	15	7	5	19	12	9
Mu et al[38], 2003	24	RIA	37	4	3	5	12	15	10
Cwik et al[39], 2004	150	RIA	37	82	5	16	47	16	11
Jiang et al[40], 2004	148	ELISA	37	82	7	14	45	17	12
Ventrucci et al[41], 2004	81	EIA	60	45	2	15	19	18	12
Teich et al[42], 2005	59	ELISA	22	27	3	3	13	12	9
Chang et al[43], 2007	111	ELISA	37	63	11	9	28	18	12
		ELISA	100	57	7	15	32	18	12
Kuhlmann et al[44], 2007	62	EIA	37	17	4	11	30	16	11
Liao et al[45], 2007	150	ELISA	37	84	15	28	23	15	10
Bedi et al[46], 2009	84	ELISA	37	23	15	11	35	17	12
		ELISA	100	14	7	20	43	17	12
Firpo et al[47], 2009	107	ELISA	37	58	2	17	30	18	12
Liao et al[48], 2009	102	RIA	37	47	22	11	22	16	10
Morris-Stiff et al[49], 2009	188	ELISA	37	70	31	3	84	19	13
Talar-Wojnarowska et al[50], 2010	157	ELISA	37	71	18	14	54	17	12
Zapico-Muñiz et al[51], 2010	102	LIA	100	35	7	12	48	16	11
Chung et al[52], 2011	78	NR	30	40	2	15	21	12	9
Gold et al[53], 2013	284	EIA	37	180	16	54	34	18	11
Kaur et al[54], 2013	114	RIA	37	76	9	15	14	17	11

CA19-9: Carbohydrate antigen 19-9; EIA: Enzyme immunoassay; ELISA: Enzyme-linked immunosorbent assay; FN: False negative; FP: False positive; LIA: Luminescent immunoassay; NR: Not reported; RIA: Radioimmunoassay; TN: True negative; TP: True positive.

Table 2 Additional characteristics of patients and methodology in the included studies

Ref.	Country/area	PC/CP, n	PC reference	Cross-sectional design	Consecutive or Random sampling	Blinded design	Prospective design
Wang et al[21], 1986	Taiwan	24/34	His or Cyt	No	Yes	No	Yes
Safi et al[22], 1987	Germany	87/104	His	Yes	Yes	No	Yes
Sakamoto et al[23], 1987	Japan	30/27	His	No	Yes	No	Yes
Friess et al[24], 1993	Germany	59/95	His	Yes	Yes	No	Yes
Röthlin et al[25], 1993	Switzerland	68/29	His	No	Yes	No	Yes
Haglund et al[26], 1994	Finland	179/20	His	No	Yes	No	Yes
Kuno et al[27], 1994	Japan	47/70	His	Yes	Yes	No	Yes
Pasquali et al[28], 1994	Italy	58/45	His	No	No	NR	Yes
Satake et al[29], 1994	Japan	641/300	His	Yes	Yes	No	Yes
Hámori et al[30], 1997	Hungary	62/32	His	No	Yes	No	Yes
Safi et al[31], 1997	Germany	347/300	His or Bio	Yes	Yes	No	Yes
Hayakawa et al[32], 1999	Japan	27/49	His (Bio, Aut)	No	Yes	No	Yes
Kim et al[33], 1999	Korea	90/70	His	Yes	Yes	No	Yes
Manes et al[34], 1999	Italy	34/24	His or Cyt	Yes	Yes	No	Yes
Slesak et al[35], 2000	Poland	48/74	His	No	Yes	No	Yes
Maire et al[36], 2002	France	47/31	His or Cyt	No	Yes	No	Yes
Akashi et al[37], 2003	Japan	20/26	His or Aut	No	Yes	No	Yes
Mu et al[38], 2003	China	9/15	His or Cyt	No	Yes	No	Yes
Cwik et al[39], 2004	Lublin	98/52	His	NR	Yes	NR	Yes
Jiang et al[40], 2004	China	96/52	His	Yes	Yes	No	Yes
Ventrucci et al[41], 2004	Italy	60/21	His	Yes	Yes	No	Yes
Teich et al[42], 2005	Germany	30/16	His	No	No	No	Yes
Chang et al[43], 2007	Taiwan	72/39	His	Yes	Yes	No	Yes
	New York, United States	28/34	His	No	Yes	NR	Yes
Kuhlmann et al[44], 2007	China	112/38	His	No	Yes	No	Yes
Liao et al[45], 2007	India	34/50	His or Bio	Yes	Yes	No	Yes
Bedi et al[46], 2009	United States	75/32	His or Cyt	Yes	Yes	No	Yes
	Taiwan	58/44	His	Yes	Yes	No	Yes
Firpo et al[47], 2009	United Kingdom	73/115	His	Yes	Yes	No	Yes
Liao et al[48], 2009	Poland	85/72	His	Yes	Yes	No	Yes
Morris-Stiff et al[49], 2009	Spain	47/55	His	Yes	Yes	No	Yes
Talar-Wojnarowska et al[50], 2010	Korea	55/23	His	Yes	Yes	No	Yes
Zapico-Muñiz et al[51], 2010	New York, United States	234/50	His or Cyt	Yes	Yes	No	Yes
Chung et al[52], 2011	Germany	91/23	His	No	Yes	No	Yes

Aut: Autopsy; Bio: Biopsy; CP: Chronic pancreatitis; Cyt: Cytology; PC: Pancreatic carcinoma; His: Histology; NR: Not reported.

Table 3 Bivariate estimates of diagnostic precision based on different carbohydrate antigen 19-9 assay methods and cut-off values

Assay method or cut-off value	Number of studies	Number of participants	Sensitivity (95%CI)	Specificity (95%CI)	PLR (95%CI)	NLR (95%CI)	DOR (95%CI)
ELISA	11	1396	0.83 (0.80-0.86)	0.79 (0.75-0.82)	3.97 (2.96-5.33)	0.20 (0.15-0.28)	22.64 (12.44-41.22)
RIA	17	3074	0.82 (0.80-0.84)	0.81 (0.79-0.83)	4.16 (3.09-5.60)	0.23 (0.19-0.27)	20.14 (13.27-30.55)
EIA	3	427	0.75 (0.70-0.80)	0.79 (0.70-0.86)	3.84 (1.82-8.10)	0.34 (0.27-0.43)	10.29 (4.96-21.34)
LIA	2	224	ND	ND	ND	ND	ND
Cut-off of 37 U/mL	30	4879	0.82 (0.80-0.83)	0.80 (0.78-0.82)	3.94 (3.24-4.78)	0.24 (0.21-0.28)	18.79 (13.67-25.82)
Cut-off of 100 U/mL	3	297	0.69 (0.61-0.76)	0.85 (0.79-0.91)	4.35 (2.86-6.61)	0.38 (0.18-0.77)	11.53 (4.47-29.77)
All studies	34	5115	0.81 (0.80-0.83)	0.81 (0.79-0.82)	4.08 (3.39-4.91)	0.24 (0.21-0.28)	19.31 (14.40-25.90)

DOR: Diagnostic odds ratio; EIA: Enzyme immunoassay; ELISA: Enzyme-linked immunosorbent assay; LIA: Luminescent immunoassay; ND: Not done; NLR: Negative likelihood ratio; PLR: Positive likelihood ratio; RIA: Radioimmunoassay.

Table 4 Weighted meta-regression of the effects of study design, methodological quality and assay parameters on diagnostic accuracy of carbohydrate antigen 19-9

Covariate	Number of studies	Coefficient	RDOR (95%CI)	P value
Study design and quality
STARD ≥ 13	30	0.564	1.76 (0.14-22.68)	0.652
QUADAS ≥ 10	29	-0.666	0.51 (0.06-4.11)	0.514
Consecutive or random design	32	0.924	2.52 (0.26-24.68)	0.411
Cross-sectional design	18	-0.512	0.60 (0.28-1.28)	0.178
Blinded design	0	ND	ND	ND
Prospective design	34	ND	ND	ND
Assay method or cut-off value
RIA	17	-0.619	0.54 (0.12-2.51)	0.413
ELISA	11	-0.737	0.48 (0.10-2.26)	0.336
EIA	3	0.425	1.53 (0.29-8.14)	0.604
Cut-off of 37 U/mL	30	0.553	1.74 (0.36-8.36)	0.474
Cut-off of 100 U/mL	3	0.890	2.43 (0.72-8.26)	0.146

EIA: Enzyme immunoassay; ELISA: Enzyme-linked immunosorbent assay; ND: Not done; RIA: Radioimmunoassay; STARD: Standards for Reporting Diagnostic Accuracy; QUADAS: Quality Assessment for Studies of Diagnostic Accuracy.