How to examine anastomotic integrity intraoperatively in totally laparoscopic radical gastrectomy? Methylene blue testing prevents technical defect-related anastomotic leaks

Table 1 Demographic, surgical, and tumor characteristics of patients according to whether an intraoperative methylene blue testing was performed or not

Variable		IMBT group (211 cases)	Control group (302 cases)	χ2	P value
Gender	Male	130	182	0.095	0.759
	Female	81	120
Age (yr)	< 75	143	196	0.457	0.499
	≥ 75	68	106
BMI (kg/m2)	< 25	155	211	0.784	0.376
	≥ 25	56	91
Preoperative complications	Present absent	88123	111191	1.282	0.257
Neoadjuvant chemotherapy	Present absent	43168	61241	0.003	0.960
Degree of tumor differentiation	High	72	92	0.785	0.672
	Medium	95	142
	Low	44	68
Postoperative tumor pathological stage1	I	32	62	3.298	0.192
	II	62	94
	III	117	146
Surgeon’s experience	< 50 cases	21	24	0.624	0.429
	≥ 50 cases	190	278
Mode of surgery	TLTG	101	146	0.025	0.875
	TLDG	111	156
Operation time	< 4h	143	189	1.465	0.226
	≥ 4h	68	113
Amount of bleeding ≥ 400 mL	Present	79	100	1.024	0.312
	Absent	132	202

¹According to the 8^th AJCC TNM staging system for gastric cancer. IMBT: Intraoperative methylene blue testing; TLTG: Totally laparoscopic total gastrectomy; BMI: Body mass index; TLDG: Totally laparoscopic distal gastrectomy.

Table 2 Characteristics of positive intraoperative methylene blue testing

Patient No.	Location of leak on anastomotic wall	Operation model	Dehiscence	Management	PAL	Postoperative hospital stays (d)
1	Posterior wall	TLTG	Present	Suturing	No	10
2	Posterior wall	TLTG	Absent	Suturing	No	9
3	Posterior wall	TLTG	Absent	Suturing	No	11
4	Joint opening	TLTG	Absent	Suturing	No	10
5	Joint opening	TLTG	Absent	Suturing	No	11
6	Left wall	TLDG	Absent	Suturing	No	12
7	Left wall	TLDG	Present	Suturing	No	9

IMBT: Intraoperative methylene blue testing; PAL: Postoperative anastomotic leak; TLTG: Totally laparoscopic total gastrectomy; TLDG: Totally laparoscopic distal gastrectomy.

Table 3 Clinicopathological characteristics of the patients according to the results of intraoperative methylene blue testing and postoperative anastomotic leaks

Variable	IMBT group	IMBT		P value	Control group	PAL		P value
		Negative	Positive (%)			Negative	Positive (%)
Cases	211	204	7 (3.3)	-	302	289	13(4.3)	-
Gender
Male	130	126	4 (3.1)	1.0	182	173	9 (4.9)	0.575
Female	81	78	3 (3.7)		120	116	4 (3.3)
Age (yr)
< 75	143	139	4 (2.8)	0.541	196	191	5 (2.6)	0.70
≥ 75	68	65	3 (4.4)		106	98	8 (7.5)
BMI (kg/m2)
< 25	155	153	2 (1.3)	0.021	211	206	5 (2.4)	0.025
≥ 25	56	51	5 (8.9)		91	83	8 (8.8)
Preoperative complications
Absent	123	120	3 (2.4)	0.454	191	187	4 (2.0)	0.018
Present	88	84	4 (4.5)		111	102	9 (8.1)
Neoadjuvant chemotherapy
Absent	168	165	3 (1.8)	0.033	241	234	7 (2.9)	0.028
Present	43	39	4 (9.3)		61	55	6 (9.8)
Degree of tumor differentiation
High	72	70	2 (2.8)	0.784	92	88	4 (4.3)	1.000
Medium	95	92	3 (3.2)		142	136	6 (4.2)
Low	44	42	2 (4.5)		68	65	3 (4.6)
Postoperative tumor pathological stage1
I	32	30	2 (6.3)	0.493	62	59	3 (4.8)	0.754
II	62	60	2 (3.2)		94	89	5 (5.3)
III	117	114	3 (2.6)		146	141	5 (3.4)

¹According to the 8^th AJCC TNM staging system for gastric cancer. IMBT: Intraoperative methylene blue testing; PAL: Postoperative anastomotic leak; BMI: Body mass index.

Table 4 Surgical variables according to the results of intraoperative methylene blue testing and postoperative anastomotic leaks

Variable	IMBT group	IMBT		P value	Control group	PAL		P value
		Negative	Positive (%)			Negative	Positive (%)
Cases	211	204	7 (3.3)	-	302	289	13 (4.3)	-
Operation time (h)
< 4	143	142	1 (0.7)	0.008	184	177	7 (4.0)	0.577
≥ 4	68	62	6 (8.8)		118	112	6 (5.1)
Amount of bleeding (mL)
< 400	132	130	2 (1.5)	0.136	202	194	8 (4.0)	0.765
≥ 400	79	74	5 (6.3)		100	95	5 (5.0)
Mode of operation
TLTG	100	95	5 (5.0)	0.200	146	136	10 (6.8)	0.046
TLDG	111	109	2 (1.8)		156	153	3 (1.9)
Surgeon’s experience (cases)
< 50	21	18	3(14.3)	0.021	24	21	3 (12.5)	0.074
≥ 50	190	186	4 (2.1)		278	268	10 (3.6)

IMBT: Intraoperative methylene blue testing; PAL: Postoperative anastomotic leak; TLTG: Totally laparoscopic total gastrectomy; TLDG: Totally laparoscopic distal gastrectomy.

Table 5 Risk factors for positive intraoperative methylene blue testing and postoperative anastomotic leaks analyzed by multivariate analysis

Variable	B	Standard deviation	Wald	Exp(B)	Odds ratio (95%CI)		P value
					Lower limit	Upper limit
IMBT
BMI ≥ 25 kg/m2	2.123	0.810	6.862	8.357	1.707	40.922	0.009
Neoadjuvant chemotherapy	1.326	0.805	2.715	3.767	0.778	18.245	0.099
Operation time ≥ 4 h	4.023	1.319	9.303	55.881	4.212	741.381	0.002
Inexperienced surgeons	2.727	1.052	6.719	15.286	1.944	120.167	0.010
PAL
BMI > 25 kg/m2	1.289	0.858	2.259	3.630	0.676	19.498	0.133
Preoperative complications	2.575	1.081	5.671	13.128	1.577	109.268	0.017
Neoadjuvant chemotherapy	1.967	0.740	7.063	7.150	1.676	30.506	0.008
TLTG	2.206	1.091	4.083	9.075	1.069	77.070	0.043

IMBT: Intraoperative methylene blue testing; PAL: Postoperative anastomotic leak; BMI: Body mass index; TLTG: Totally laparoscopic total gastrectomy.

Table 6 Characteristics of postoperative anastomotic leaks

Patient No.	Group	Day of diagnosis after surgery (d)	TLTG or TLDG	Tumor staging1	Procedure used for patients	Time of placement of abdominal drainage tube (d)	Postoperative Hospital stays (d)
1	IMBT group	6	TLTG	IIB	Drainage	15	16
2	IMBT group	8	TLTG	IIIA	Second surgery + Drainage	20	21
3	Control group	4	TLTG	IA	Drainage	18	19
4	Control group	5	TLTG	IIA	Drainage	13	15
5	Control group	9	TLTG	IIB	Drainage	19	21
6	Control group	8	TLTG	IIB	Drainage	12	14
7	Control group	5	TLTG	IIIC	Drainage	18	20
8	Control group	3	TLTG	IIIC	Drainage	16	18
9	Control group	8	TLTG	IIB	Second surgery + Drainage	21	24
10	Control group	7	TLTG	IIIB	Second surgery + Drainage	22	25
11	Control group	7	TLTG	IIIC	Second surgery + Drainage	17	21
12	Control group	5	TLDG	IIIA	Drainage	12	14
13	Control group	3	TLDG	IIA	Second surgery + Drainage	17	18
14	Control group	3	TLDG	IIIA	Second surgery + Drainage	19	20
15	Control group	6	TLDG	IIIC	Second surgery + Drainage	20	23

¹According to the 8^th AJCC TNM staging system for gastric cancer. PAL: Postoperative anastomotic leak; TLTG: Totally laparoscopic total gastrectomy; TLDG: Totally laparoscopic distal gastrectomy.