Treatment for gastric ‘indefinite for neoplasm/dysplasia’ lesions based on predictive factors

Table 1 Clinicopathologic factors of the confirmed carcinoma and non-carcinoma indefinite for neoplasm/dysplasia lesions reported at the initial forceps biopsy n (%)

Initial Dx	Total n = 461	IFND		P value
Final Dx		Non-carcinoma n = 357	Carcinoma n = 104
Sex				0.816
Male	319 (69.2)	248 (69.5)	71 (68.3)
Female	142 (30.8)	109 (30.5)	33 (31.7)
Age (yr)				< 0.001
< 60	236 (51.2)	204 (57.1)	32 (30.8)
≥ 60	225 (48.8)	153 (42.9)	72 (69.2)
Endoscopic size (mm)				< 0.001
< 10	286 (62.0)	251 (70.3)	35 (33.7)
≥ 10	175 (38.0)	106 (29.7)	69 (66.3)
Location I				0.914
Upper	43 (9.3)	34 (9.5)	9 (8.7)
Middle	122 (26.5)	93 (26.1)	29 (27.9)
Lower	296 (64.2)	230 (64.4	66 (63.5)
Location II				0.744
Fundus	9 (1.9)	8 (2.2)	1 (1.0)
Body	122 (26.5)	93 (26.1)	29 (27.9)
Antrum	277 (60.1)	213 (59.7)	64 (61.5)
Angle	53 (11.5)	43 (12.0)	10 (9.6)
Location III				0.267
Anterior wall	75 (16.3)	55 (15.4)	20 (19.2)
Posterior wall	76 (16.5)	63 (17.6)	13 (12.5)
Greater curvature	85 (18.4)	61 (17.1)	24 (23.1)
Lesser curvature	225 (48.8)	178 (49.9)	47 (45.2)
Gross type				0.585
Elevated (type I and IIa)	181 (39.3)	136 (38.1)	45 (43.3)
Flat (type IIb)	168 (36.4)	134 (37.5)	34 (32.7)
Depressed (type IIc and III)	112 (24.3)	87 (24.4)	25 (24.0)
Color change				0.140
Redness	314 (68.1)	250 (70.0)	64 (61.5)
Whitish	58 (12.6)	45 (12.6)	13 (12.5)
No change	89 (19.3)	62 (17.4)	27 (26.0)
Single lesion				< 0.001
No	141 (30.6)	134 (37.5)	7 (6.7)
Yes	320 (69.4)	223 (62.5)	97 (93.3)
Ulcer				0.182
No	334 (72.5)	264 (73.9)	70 (67.3)
Yes	127 (27.5)	93 (26.1)	34 (32.7)
Spontaneous bleeding				< 0.001
No	405 (87.9)	332 (93.0)	73 (70.2)
Yes	56 (12.1)	25 (7.0)	31 (29.8)
Fold change				0.206
No	418 (90.7)	327 (91.6)	91 (87.5)
Yes	43 (9.3)	30 (8.4)	13 (12.5)
Initial Bx				< 0.001
Regenerating atypia	276 (59.9)	267 (74.8)	9 (8.7)
Atypical epithelium	185 (40.1)	90 (25.2)	95 (91.3)
Repeated IFND				0.002
No	436 (94.6)	344 (96.4)	92 (88.5)
Yes	25 (5.4)	13 (3.6)	12 (11.5)
Bx numbers at initial endoscopic Bx		1.77 ± 1.13	2.15 ± 1.37	0.013

Dx: Diagnosis; IFND: Indefinite for neoplasm/dysplasia; Bx: Biopsy.

Table 2 Predictive factors of gastric carcinoma in the univariate and multivariate analyses

	Univariate		Multivariate
	OR (95%CI)	P value	OR (95%CI)	P value
Age (yr) (< 60 vs ≥ 60)	3.000 (1.882-4.782)	< 0.001	2.445 (1.305-4.580)	0.005
Endoscopic gross size (mm) (< 10 vs ≥ 10)	4.631 (2.906-7.380)	< 0.001	3.519 (1.891-6.548)	< 0.001
Multiple vs single lesion	8.327 (3.755-18.465)	< 0.001	5.702 (2.212-14.696)	< 0.001
Spontaneous bleeding (Absent vs Present)	5.639 (3.143-10.119)	< 0.001	4.056 (1.792-9.180)	0.001
Initial Bx (Regenerating atypia vs Atypical epithelium)	31.315 (15.180-64.599)	< 0.001	25.575 (11.537-56.695)	< 0.001
Repeated IFND (No vs Yes)	3.750 (1.631-8.622)	0.002	6.022 (1.822-19.909)	0.003

OR: Odds ratio; CI: Confidence interval; Bx: Biopsy; IFND: Indefinite for neoplasm/dysplasia.

Table 3 Clinicopathologic factors of poor prognosis carcinoma in the subgroup analysis of the carcinoma group n (%)

Initial Dx	Total n = 104	Carcinoma group		P value
Final Dx		Non-poor prognostic carcinoma n = 75	Poor prognostic carcinoma n = 29
Sex				0.924
Male	71 (68.3)	51 (68.0)	20 (69.0)
Female	33 (31.7)	24 (32.0)	9 (31.0)
Age (yr)				0.053
< 60	32 (30.8)	19 (25.3)	13 (44.8)
≥ 60	72 (69.2)	56 (74.7)	16 (55.2)
Endoscopic size (mm)				0.082
< 10	35 (33.7)	29 (38.7)	6 (20.7)
≥ 10	69 (66.3)	46 (61.3)	23 (79.3)
Location I				0.162
Upper	9 (8.7)	7 (9.3)	2 (6.9)
Middle	29 (27.9)	17 (22.7)	12 (41.4)
Lower	66 (63.5)	51 (68.0)	15 (51.7)
Gross type				0.034
Elevated (type I and IIa)	45 (43.3)	36 (48.0)	9 (31.0)
Flat (type IIb)	34 (32.7)	26 (34.7)	8 (27.6)
Depressed (type IIc and III)	25 (24.0)	13 (17.3)	12 (41.4)
Color change				0.745
Redness	64 (61.5)	45 (60.0)	19 (65.5)
Whitish	13 (12.5)	9 (12.0)	4 (13.8)
No change	27 (26.0)	21 (28.0)	6 (20.7)
Single lesion				0.186
No	7 (9.3)	7 (6.7)	0 (0)
Yes	97 (93.3)	68 (90.7)	29 (100)
Ulcer				0.010
No	70 (67.3)	56 (74.7)	14 (48.3)
Yes	34 (32.7)	19 (25.3)	15 (51.7)
Spontaneous bleeding				0.517
No	73 (70.2)	54 (72.0)	19 (65.5)
Yes	31 (29.8)	21 (28.0)	10 (34.5)
Fold change				0.001
No	91 (87.5)	71 (94.7)	20 (69.0)
Yes	13 (12.5)	4 (5.3)	9 (31.0)
Initial Bx				0.707
Regenerating atypia	9 (8.7)	6 (8.0)	3 (10.3)
Atypical epithelium	95 (91.3)	69 (92.0)	26 (89.7)
Repeated IFND				1.000
No	92 (88.5)	66 (88.0)	26 (89.7)
Yes	12 (11.5)	9 (12.0)	3 (10.3)

Dx: Diagnosis; IFND: Indefinite for neoplasm/dysplasia; Bx: Biopsy.

Table 4 Predictive factors of poor prognosis carcinoma in the univariate and multivariate analyses

	Univariate		Multivariate
	OR (95%CI)	P value	OR (95%CI)	P value
Depressed Gross type (No vs Yes)	3.367 (1.301-8.710)	0.034	1.946 (0.621-6.104)	0.254
Ulceration (Absent vs Present)	3.158 (1.290-7.729)	0.010	1.746 (0.594-5.130)	0.311
Fold change (Absent vs Present)	7.988 (2.225-28.672)	0.001	5.594 (1.458-21.462)	0.012

OR: Odds ratio; CI: Confidence interval.

Table 5 Diagnostic delays in gastric carcinoma and the clinicopathologic correlation n (%)

	Early	Delayed	P	Early	Delayed	P	Early	Delayed	P	Early	Delayed	P
	(≤ 2 wk)	(> 2 wk)		(≤ 2 mo)	(> 2 mo)		(≤ 6 mo)	(> 6 mo)		(≤ 1 yr)	(> 1 yr)
	n = 28	n = 76		n = 73	n = 31		n = 96	n = 8		n = 97	n = 7
Initial Bx			0.109			< 0.001			< 0.001			0.112
RegA	0 (0)	9 (11.8)		1 (1.4)	8 (25.8)		1 (1.4)	8 (25.8)		7 (7.2)	2 (28.6)
AGL	28 (100)	67 (88.2)		72 (98.6)	23 (74.2)		72 (98.6)	23 (74.2)		90 (92.8)	5 (71.4)
Repeated IFND			0.033			0.001			0.048			0.032
No	28 (100)	64 (84.2)		70 (95.9)	22 (71.0)		87 (90.6)	5 (62.5)		88 (90.7)	4 (57.1)
Yes	0 (0)	12 (15.8)		3 (4.1)	9 (29.0)		9 (9.4)	3 (37.5)		9 (9.3)	3 (42.9)
Differentiation			1.000			0.729			1.000			0.554
Differ	25 (89.3)	68 (89.5)		66 (90.4)	27 (87.1)		86 (89.6)	7 (87.5)		87 (89.7)	6 (85.7)
Undiffer	3 (10.7)	8 (10.5)		7 (9.6)	4 (12.9)		10 (10.4)	1 (12.5)		10 (10.3)	1 (14.3)
Tumor size (pathology)			0.252			0.444			0.602			1.000
< 10 mm	6 (24.0)	27 (36.5)		21 (30.9)	12 (38.7)		31 (34.1)	2 (25.0)		31 (33.7)	2 (28.6)
≥ 10 mm	19 (76.0)	47 (63.5)		47 (69.1)	19 (61.3)		60 (65.9)	6 (75.0)		61 (66.3)	5 (71.4)
Invasion depth			0.103			0.395			0.197			0.341
≤ Mucosa	19 (67.9)	62 (82.7)		55 (76.4)	26 (83.9)		73 (76.8)	8 (100)		74 (77.1)	7 (100)
≥ Submucosa	9 (32.1)	13 (17.3)		17 (23.6)	5 (16.1)		22 (23.2)	0 (0)		22 (22.9)	0 (0)
LVI			1.000			0.581			0.278			0.246
No	27 (96.4)	73 (96.1)		71 (97.3)	29 (93.5)		93 (96.9)	7 (87.5)		94 (96.9)	6 (85.7)
Yes	1 (3.6)	3 (3.9)		2 (2.7)	2 (6.5)		3 (3.1)	1 (12.5)		3 (3.1)	1 (14.3)
Complete resection			0.033			1.000			1.000			1.000
No	5 (17.9)	3 (4.0)		6 (8.3)	2 (6.5)		8 (8.4)	0 (0)		8 (8.3)	0 (0)
Yes	23 (82.1)	72 (96.0)		66 (91.7)	29 (93.5)		87 (91.6)	8 (100)		88 (91.7)	7 (100)
Additional surgery			0.031			1.000			1.000			1.000
No	23 (82.1)	73 (96.1)		67 (91.8)	29 (93.5)		88 (91.7)	8 (100)		89 (91.8)	7 (100)
Yes	5(17.9)	3(3.9)		6(8.2)	2(6.5)		8(8.3)	0(0)		8(8.2)	0(0)
Recurrence			0.562			1.000			0.215			0.190
No	28 (100)	73 (96.1)		71 (97.3)	30 (96.8)		94 (97.9)	7 (87.5)		95 (97.9)	6 (85.7)
Yes	0 (0)	3 (3.9)		2 (2.7)	1 (3.2)		2 (2.1)	1 (12.5)		2 (2.1)	1 (14.3)
Endoscopic suspicion for carcinoma			0.003			0.016			1.000			1.000
No	10 (35.7)	52 (68.4)		38 (52.1)	24 (77.4)		57 (59.4)	5 (62.5)		58 (59.8)	4 (57.1)
Yes	18 (64.3)	24 (31.6)		35 (47.9)	7 (22.6)		39 (40.6)	3 (37.5)		39 (40.2)	3 (42.9)

Bx: Biopsy; IFND: Indefinite for neoplasm/dysplasia; LVI: Lymphovascular invasion; AGL: Atypical epithelium; RegA: Regenerating atypia; Differ: Differentiated adenocarcinoma; Undiffer: Un-differentiated adenocarcinoma.

Table 6 Retrospective prediction rate for the final diagnosis of 24 cases of repeated indefinite for neoplasm/dysplasia by five pathologists in a blinded H and E slide review

	Sex	Age (yr)	Bx N	Original report		Final Dx	Review and Dx rate
				1st Bx	2nd Bx		1st Bx	2nd Bx
1	M	80	2	AGL	AGL	W/D	60%	0%
2	F	78	2	RegA	RegA	Gastritis	100%	100%
3	M	78	2	AGL	AGL	W/D	60%	80%
4	F	76	2	AGL	RegA	W/D	20%	20%
5	M	75	2	AGL	AGL	W/D	80%	20%
6	M	72	2	RegA	AGL	W/D	0%	20%
7	M	72	3	RegA	AGL	W/D	100%	40%
8	M	68	2	AGL	AGL	W/D	100%	100%
9	F	67	2	RegA	AGL	Gastritis	80%	60%
10	M	66	2	RegA	RegA	Adenoma	100%	100%
11	M	66	2	AGL	AGL	Gastritis	60%	40%
12	M	61	3	AGL	AGL	Gastritis	60%	0%
13	M	60	2	AGL	AGL	W/D	0%	80%
14	F	59	2	AGL	AGL	W/D	80%	60%
15	M	59	4	RegA	RegA	Gastritis	100%	40%
16	M	57	3	RegA	RegA	Adenoma	20%	20%
17	M	56	2	AGL	AGL	Adenoma	80%	80%
18	M	56	2	AGL	AGL	W/D	20%	30%
19	M	55	2	RegA	RegA	Gastritis	100%	100%
20	F	54	3	AGL	RegA	W/D	0%	0%
21	M	51	3	AGL	RegA	W/D	0%	0%
22	M	51	3	RegA	RegA	Adenoma	100%	100%
23	M	49	2	RegA	RegA	Gastritis	20%	100%
24	M	42	2	RegA	RegA	Gastritis	80%	80%
Final Dx				1st Bx (A)	2nd Bx (A)	C	κ	P
Gastritis			n = 8	75.0%	60.8%	0.791	0.117	0.463
Adenoma			n = 4	78.3%	84.2%	1.000	0.733	0.001
Adenocarcinoma			n = 12	65.0%	63.3%	0.629	0.415	0.001

H and E: Hematoxylin and eosin; IFND: Indefinite for neoplasm/dysplasia; Bx: Biopsy; Dx: Diagnosis; W/D: Well-differentiated adenocarcinoma; A: Accuracy; C: Concordance; AGL: Atypical epithelium; RegA: Regenerating atypia.