Surgery combined with intraoperative hyperthermic intraperitoneal chemotherapy (IHIC) for gastric cancer: A systematic review and meta-analysis of randomised controlled trials

Figures & data

Figure 1. Selection process for RCTs of RS combined with IHIC for resectable AGC.

Table I.  Trial design and baseline characteristics of studies included.

Study and year	N	Study type	Gastric cancer	Characteristics of patients	Surgery	Treatment of experimental group	Treatment of control
Chen et al., 2006 [3]	140	RCT	Primary AGC	With serosal invasion but without peritoneal metastasis	Radical	IHIC with CDDP and 5-Fu	RS alone
Chen et al., 2005 [4]	60	RCT	Primary AGC	With serosal invasion but without peritoneal metastasis	Radical	IHIC with CDDP and 5-Fu	RS alone
Chen et al., 2001 [5]	60	RCT	Primary AGC	With serosal invasion but without peritoneal metastasis	Radical	IHIC with CDDP	RS alone
Fujimoto et al., 1999 [6]	141	RCT	Primary AGC	With serosal invasion but without peritoneal metastasis	Radical	IHIC with MMC	RS alone
Fujimura et al., 1994 [7]	58	RCT	Primary AGC	With serosal invasion but without peritoneal metastasis	Radical	IHIC with CDDP and MMC	RS alone
Hamazoe et al., 1994 [8]	82	RCT	Primary AGC	With serosal invasion but without peritoneal metastasis	Radical	IHIC with MMC	RS alone
Jin, 2007 [9]	116	RCT	Primary AGC	With serosal invasion but without peritoneal metastasis	Radical	IHIC with CDDP and MMC	RS alone
Wang et al., 2006 [10]	68	RCT	Primary AGC	With serosal invasion but without peritoneal metastasis	Radical	IHIC with CDDP	RS alone
Wang et al., 2002 [11]	228	RCT	Primary AGC	With serosal invasion but without peritoneal metastasis	Radical	IHIC with MMC and 5-Fu	RS alone
Wang, 2010 [12]	116	RCT	Primary AGC	With serosal invasion but without peritoneal metastasis	Radical	IHIC with CDDP and 5-Fu	RS alone
Ye et al., 2007 [13]	203	RCT	Primary AGC	With serosal invasion but without peritoneal metastasis	Radical	IHIC with CDDP and 5-Fu	RS alone
Yonemura et al., 1995 [14]	160	RCT	Primary AGC	With serosal invasion but without peritoneal metastasis	Radical	IHIC with CDDP and MMC	RS alone
Yonemura et al., 2001 [15]	139	RCT	Primary AGC	With serosal invasion but without peritoneal metastasis	Radical	IHIC with CDDP and MMC	RS alone
Zhang et al., 2007 [16]	212	RCT	Primary AGC	With serosal invasion but without peritoneal metastasis	Radical	IHIC with CDDP and MMC	RS alone
Zhan et al., 2010 [17]	60	RCT	Primary AGC	With serosal invasion but without peritoneal metastasis	Radical	IHIC with CDDP	RS alone
Zhang et al., 1998 [18]	63	RCT	Primary AGC	With serosal invasion but without peritoneal metastasis	Radical	IHIC with 5-Fu and DDW	RS alone

AGC, Advanced gastric cancer; CDDP, Cisplatin; DDW, Double distilled water; IHIC, Intraoperative hyperthermic intraperitoneal chemotherapy; MMC, Mitomycin; N, Number of patients; RCT, Randomised controlled trial; RS, Radical surgery; 5-Fu, Fluorouracil.

Table II.  Quality assessment of RCTs included for meta-analysis.

Study and year	Truly random	Allocation concealment	Baseline features	Loss to follow-up	ITT analysis	Eligibility criteria
Chen et al., 2006 [3]	Yes	Yes	Adequate	No	No	Adequate
Chen et al., 2005 [4]	Unclear	Unclear	Adequate	Yes (N = 4)	No	Adequate
Chen et al., 2001 [5]	Unclear	Unclear	Adequate	Unclear	No	Adequate
Fujimoto et al., 1999 [6]	Yes	Yes	Adequate	Unclear	Yes	Adequate
Fujimura et al., 1994 [7]	Yes	Yes	Adequate	Unclear	Yes	Adequate
Hamazoe et al., 1994 [8]	Yes	Yes	Adequate	Unclear	Yes	Adequate
Jin, 2007 [9]	Unclear	Unclear	Adequate	Unclear	No	Adequate
Wang et al., 2006 [10]	Unclear	Unclear	Adequate	No	No	Adequate
Wang et al., 2002 [11]	Unclear	Unclear	Adequate	Unclear	No	Adequate
Wang, 2010 [12]	Unclear	Unclear	Adequate	Unclear	No	Adequate
Ye et al., 2007 [13]	Unclear	Unclear	Adequate	No	No	Adequate
Yonemura et al., 1995 [14]	Yes	Yes	Adequate	Unclear	Yes	Adequate
Yonemura et al., 2001 [15]	Yes	Yes	Adequate	Unclear	Yes	Adequate
Zhang et al., 2007 [16]	Yes	Yes	Adequate	No	No	Adequate
Zhan et al., 2010 [17]	Yes	Yes	Adequate	Yes (N = 1)	Yes	Adequate
Zhang et al., 1998 [18]	Unclear	Unclear	Adequate	Unclear	No	Adequate

Figure 2. Meta-analysis of overall survival rate for patients in the two groups.

Table III.  Meta-analysis of recurrence rate and safety for patients in the two arms.

		IHIC		Control		Heterogeneity		Statistical	Result of meta-analysis
Outcome	Included studies	n	N	n	N	I^2 %	P	method	RR (95%CI)	P
1-year recurrence rate	2 [6], [17]	6	101	9	100	0	0.81	M-H, fixed	0.66 (0.25, 1.78)	0.41
2-year recurrence rate	3 [6], [9], [16]	31	221	84	248	0	0.78	M-H, fixed	0.42 (0.29, 0.61)	<0.00001
3-year recurrence rate	5 [3], [6], [7], [12], [17]	30	249	84	248	0	0.45	M-H, fixed	0.35 (0.24, 0.51)	<0.00001
5-year recurrence rate	8 [3], [6], [8], [10–13], [15]	111	555	228	518	0	0.45	M-H, fixed	0.47 (0.39, 0.56)	<0.00001
Abdominal pain	4 [3], [4], [9], [12]	40	212	0	218	0	0.78	M-H, fixed	21.46 (5.24, 87.78)	<0.00001
Anastomotic leakage	6 [6–8], [10], [14], [15]	10	299	11	287	0	0.98	M-H, fixed	0.86 (0.38, 1.95)	0.72
Ileus	2 [10], [15]	3	85	1	78	0	0.78	M-H, fixed	2.08 (0.32, 13.55)	0.45
Bowel perforation	2 [7], [15]	2	70	0	65	0	0.94	M-H, fixed	2.70 (0.29, 25.15)	0.38
Myelosuppression	3 [3], [12], [14]	13	205	12	211	0	0.79	M-H, fixed	1.10 (0.53, 2.29)	0.80
Gastrointestinal reaction	2 [3], [12]	26	126	22	130	0	0.94	M-H, fixed	1.23 (0.73, 2.05)	0.44
Hypohepatia	2 [3], [12]	4	126	1	130	0	0.57	M-H, fixed	3.09 (0.50, 18.87)	0.22

CI, Confidence interval; IHIC, Intraoperative hyperthermic intraperitoneal chemotherapy; M-H, Mantel-Haenszel; RR, Relative risk.

Figure 3. Funnel plot analysis.

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