Cytoreductive surgery and intraperitoneal chemotherapy for colorectal peritoneal metastases

Table 1 Summary of study design, treatment indications and treatment protocols for studies included in systematic review process n (%)

Ref.	Time frame	n	Study design (evidence level)	Indication	Extent of CPM	Treatment summary	Technique	Intraperitoneal chemotherapeutic regimen
Portilla et al[33]	1985-1996	18	Case series (3)	rCPM1	PCI < 12, 10/18 (60)	CRS + EPIC	Closed technique	POD 1: MMC in 1 L 1.5% dextrose peritoneal dialysis solution (10-12.5 mg/m2)
					PCI > 12, 8/18 (38)			POD 2-6: 5-FU in 1 L 1.5% dextrose peritoneal dialysis solution + 50 mEq sodium bicarbonate
Witkamp et al[34]	1995-1997	29	Case series (3)	CPM2	-	CRS + HIPEC	Closed technique	MMC 35 mg/m2 in 3-4 L of isotonic dialysis fluid at a temperature of 40 °C-41 °C for 90 min
Pilati et al[35]	1995-2001	34	Case series (3)	CPM2	-	CRS + HIPEC	10/34 closed technique	MMC (3.3 mg/m2 per liter) + cisplatin (25 mg/m2 per liter) for 90 min at temperature of 41 °C-42 °C
							14/34 open technique
Verwaal et al[36]	1995-2003	106	Case series (3)	rCPM2	-	CRS + HIPEC	Closed abdomen technique	MMC 35 mg/m2 in 3-4 L of isotonic dialysis fluid at a temperature of 40 °C-41 °C for 90 min
Glehen et al[37]	1989-2002	53	Multicentre case series (3)	CPM2	Stage2 I 13/53 (25)	CRS + HIPEC	Closed abdomen technique	MMC 40-60 mg in 4-6 L of perfusate at a temperature of 46 °C-48 °C for 90 min
					Stage II 8/53 (15)
					Stage III 7/53 (13)
					Stage IV 25/53 (47)
Mahteme et al[53]	1991-1999	36 (18 vs 18)	Case-control (2-)	CPM2	-	Treatment arm: CRS + EPIC (n = 18)	Closed abdomen technique	EPIC protocol: 5-FU 550 mg/m2 in 500 mL normal saline administered intraperitoneally from POD 1. IV infusion of leucovorin (60 mg/m2) commenced at 60 min after initiation of PIC. Regimen offered 1-8 courses as tolerated with 4-6 wk interval between cycles.
						Control arm: Systemic CT only		Systemic CT protocol: Chemotherapeutic regimen not specified
Glehen et al[38]	1987-2002	506	Multinational case series (3)	CPM3	Limited 171/506	(n = 18)CRS + HIPEC and/or EPIC	Open or closed technique	HIPEC protocol: Various (MMC alone 274/506; MMC + cisplatin 48/506; oxaliplatin 32/506; other 29/506)
					Extended 329/506			EPIC protocol: Various (MMC alone 2/506; MMC + 5-FU 113/506; 5-FU alone 95/506; other 7/506)
Shen et al[39]	1991-2002	77	Case series (3)	CPM3	-	CRS + HIPEC		40 mg MMC introduced into dialysis fluid for 120 min at ≥ 38.5 °C
Cavaliere et al[40]	1996-2005	120	Multicentre case series (3)	CPM1	-	CRS + HIPEC	Closed abdomen technique Open 56.7%	109/120: MMC (3.3 mg/m2 per liter) and cisplatin (25 mg/m2 per liter) at 41.5 °C-43 °C for 60-90 min
							Closed 43.3%	11/120: oxaliplatin (460 mg/m2) for 30 min after IV 5-FU and leucovorin
Kianmanesh et al[41]	1996-2006	43	Case series (3)	CPM3	Stage2 I/II 10/43 (23)	CRS + HIPEC	Open technique	MMC 120 mg + cisplatin 200 mg/m2 at 41 °C-43 °C for 90 to 120 min
					Stage III 6/43 (14)
					Stage IV 27/43 (63)
Gusani et al[42]	2002-2005	28	Case series (3)	CPM2	-	CRS + HIPEC	Closed technique	MMC 30-40 mg in 3 L saline solution at temperature of 40 °C for 100 min
Verwaal et al[26]	1998-2001	105 (54 vs 51)	Randomized trial (1-)	CPM2	-	Treatment arm: CRS + HIPEC (n = 54)	Open coliseum technique	HIPEC protocol: MMC 17.5 mg/m2 at 40 °C for 90 min
						Control arm: Systemic CT only (n = 51)		Systemic CT protocol: 5-FU (400 mg/m2) + leucovorin (80 mg/m2) weekly for 26 wk
Yan et al[62]	1997-2007	50	Case series (3)	CPM3	PCI < 10 20/50	CRS + HIPEC	Open coliseum technique	MMC 10-12.5 mg/m2 in 3 L of 1.5% dextrose peritoneal dialysis solution for 90 min at 42 °C
					PCI 10-20 23/50
					PCI > 20 7/50
Elias et al[54]	1998-2003	96 (48 vs 48)	Case-control (2-)	CPM3	Treatment arm: Limited 27/48 Extended 21/48	Treatment arm: CRS + HIPEC (n = 48)	-	HIPEC protocol: Oxaliplatin 460 mg/m2 in 2 L/m2 at 43 °C for 30 min. Before HIPEC (during CRS) patients received IV 5-FU 400 mg/m2 + leucovorin 20 mg/m2
					Control arm:	Control arm:		Systemic CT protocol:
					Limited 26/48 Extended 17/48Not recorded 5/48	Systemic CT only (n = 48)		Various regimens (5-FU based 46/48; Capecitabine based 1/48; Camptothecin 1/48)
Varban et al[43]	1991-2007	142	Case series (3)	CPM3	-	CRS + HIPEC	Closed technique	MMC 40 mg at 40.5 °C-42.5 °C for 120 min
Vaira et al[44]	1997-2008	40	Case series (3)	CPM2	PCI > 16 11/40	CRS + HIPEC	Closed technique	Cisplatin (100 mg/m2) + MMC (16 mg/m2) at 41.5 °C for 30 min
					PCI < 16 29/40			OR
								Oxaliplatin (460 mg/m2) + IV 5-FU at 42 °C for 30 min
								OR
								MMC (35 mg/m2) at 40.5 °C for 60 min
Glehen et al[45]	1989-2007	523	Multi-centre case series (3)	CPM3	-	CRS + HIPEC and/or EPIC	Various techniques	HIPEC protocol: MMC (30-50 mg/m2) with or without cisplatin (50-100 mg/m2) delivered over 60-120 min at 41 °C-42.5 °C
								OR
								Oxaliplatin (360-460 mg/m2) +/- irinotecan (100-200 mg/m2) +/- IV 5-FU and leucovorin delivered over 30 min at 43 °C
								EPIC protocol: Abdominal cavity filled at the end of surgery with 1 L/m2 Ringer lactate. EPIC lasted 5 d (POD 1-5); POD 1: MMC (10 mg/m2); POD 2-5: 5FU (600 mg/m2)
Franko et al[55]	2001-2007	105 (67 vs 38)	Case-control (2-)	CPM2	-	Treatment arm: CRS+ HIPEC (n = 67)	Closed abdomen technique	HIPEC protocol: MMC 40 mg for 100 min
						Control arm: Systemic CT only (n = 38)		Systemic CT protocol: Chemotherapeutic regimen(s) not clearly described
Quenet et al[46]	1998-2007	146	Case series (3)	CPM3	PCI < 10 69/146	CRS + HIPEC	Closed technique	IV 5-FU (400 mg/m2) + leucovorin (20 mg/m2) followed by: ip oxaliplatin (460 mg/m2) in 2 L/m2 dextrose
					PCI 11-19 57/146			OR
					PCI >20 20/146			ip oxaliplatin (300 mg/m2) + ip irinotecan (200 mg/m2) in 2 L/m2 dextrose
Cashin et al[57]	1993-2008	32 (16 vs 16)	Case-control (2-)	CPM2	HIPEC group: Mean PCI 14.4	CRS + HIPEC (n = 16)	HIPEC:Open coliseum techniqueEPIC: Closed technique	HIPEC protocol: Oxaliplatin 460 mg/m2 for 30 min at 41 °C-42 °C combined with IV 5-FU (450-500 mg/m2) + leucovorin (25-30 mg/m2)
					EPIC group: Mean PCI 13.2	CRS + EPIC (n = 16)		EPIC protocol: 5-FU (500-600 mg/m2) + IV leucovorin (20-30 mg/m2) once daily for 86-d cycles
Passot et al[47]	1991-2010	120	Case series (3)	CPM3	Stage2 I-II 41/120	CRS + HIPEC	Closed technique	MMC + irinotecan or oxaliplatin
					Stage III-IV 79/120			Exact dosing protocol not described
					Mean PCI 8.2
Hompes et al[48]	2004-2008	48	Case series (3)	CPM2	Median PCI 11 (1-22)	CRS + HIPEC	Open coliseum technique	IV folinic acid (20 mg/m2) + 5-FU (400 mg/m2) followed by ip oxaliplatin (460 mg/m2) in 2 L/m2 5% glucose solution at 41 °C-42 °C for 30 min
Cashin et al[56]	1996-2010	151 (69 vs 57)	Case control (2-)	CPM3	PCI 1-10 49/151	CRS+ HIPEC (n = 69)	HIPEC: Open coliseum technique	HIPEC protocol: MMC ip (30 mg/m2) for 90 min at 41 °C-42 °C OR oxaliplatin (460 mg/m2) ip for 30 min at 41 °C-42 °C + IV 5-FU (400 mg/m2) and calcium folinate (60 mg/m2) OR oxaliplatin (360 mg/m2) ip + irinotecan (360 mg/m2) for 30 min at 41 °C-42 °C + IV 5-FU (450-500 mg/m2) and calcium folinate (60 mg/m2)
					PCI 11-20 45/151	CRS + EPIC (n = 57)	EPIC: Closed technique	EPIC protocol: 5-FU (500-600 mg/m2) ip + IV leucovorin (60 mg/m2) once daily for 8 6-d cycles
					PCI 21-39 56/151
Klaver et al[49]	1996-2010	24	Case series (3)	CPM14	-	CRS+ HIPEC (12/24)	Open coliseum technique	HIPEC protocol: ip chemotherapy (MMC or oxaliplatin; dosing not stated) at 42 °C for 90 min
						CRS + EPIC (6/24)		EPIC protocol: 5-FU (650-800 mg/m2 per day) in 1 L 1.5% dextrose for 23 h on POD 1-5
						CRS + HIPEC + EPIC (6/24)
Turrini et al[50]	2004-2010	26	Case series (3)	CPM1	-	CRS + HIPEC	Open coliseum technique	Oxaliplatin ip (460 mg/m2) in 2 L/m2 dextrose solution at 43 °C for 30 min after 1 h infusion of IV 5-FU (400 mg/m2) + leucovorin (20 mg/m2)
Haslinger et al[51]	2003-2011	38	Case series (3)	CPM2	-	CRS+ HIPEC	Closed technique	MMC 40 mg at temperature of 41 °C for 60-120 min
Yonemura et al[52]	2004-2012	142	Case series (3)	CPM3	-	CRS + HIPEC	-	MMC 20 mg/m2 + cisplatin 100 mg/m2 in $L saline at 42 °C-43 °C for 60 min

¹Not stated clearly whether patients with distant metastases to other sites included/excluded;

²Patients with distant metastases excluded;

³Cases with extra-abdominal metastatic involvement excluded (LN positive and liver metastasised cases included);

⁴All patients ≥ 70 years of age. PCI: Peritoneal cancer index; CRS: Cytoreductive surgery; EPIC: Early post-operative intraperitoneal chemotherapy; POD: Postoperative day; MMC: Mytomycin C; HIPEC: Hyperthermic intra-peritoneal chemotherapy.

Table 2 Oncological outcome data n (%)

Ref.	Median FU (mth)	Pre-op CT	Post-op CT	Extent of cytoreduction/disease CCRS2	1-yr survival	2-yr survival	3-yr survival	4-yr survival	5-yr survival	Median survival (mo)	Local/distant recurrence
Portilla et al[33]	36.21	22% (regimen not stated)	100% (regimen not stated)	CC0-CC1 (14/18; 64)	CC0-CC1 (91%)	CC0-CC1 (64%)	-	-	-	Overall	-
				CC2-CC3 (4/18; 36)	CC2-CC3 (43%)	CC2-CC3 (14%)				20
				PCI < 12 (10/18; 56)	PC1 < 12 (N/A)	PCI < 12 (64%)
				PCI > 12 (8/18; 44)	PCI > 12 (N/A)	PCI > 12 (14%)
Witkamp et al[34]	38 (26-52)	-	72% (5-FU+ leucovorin)	-	82%	45%	23%	-	-	-	LR 28%
											DR 17%
											LR + DR 28%
Pilati et al[35]	14.5 (6-34)	0%	-	CC0-1 34/34	68%	31%	-	-	-	18	LR 59%
											DR 12%
											LR + DR 18%
Verwaal et al[36]	47.5 (1.3-88.3)	-	15% (leucovorin)	R1 (54/106; 51)	-	-	-	-	-	R1 11.1	Unspecified recurrence 65%
				R2a (37/106; 35)						R2a 5.9
				R2b (15/106; 14)						R2b 3.7
Glehen et al[37]	59.5	-	68% (5-FU + irinotecan leucovorin)	CC0 (23/53; 43)	CC0 85%	CC0 54%	-	-	CC0 22%	CC0 32.9	Unspecified recurrence 19%
				CC1 (11/53; 21)	CC1 46%	CC1 36%			CC1 9%	CC1 12.5
				CC2 (19/53; 36)	CC2 24%	CC2 0%				CC2 8.1
Mahteme et al[53]	-	-	-	CC0 (11/18; 61)	-	CRS + EPIC 60%	-	-	CRS + EPIC 28%	CRS + EPIC overall 32; CC0 34.5 CC1-2 10	-
				CC1-2 (7/18; 39)		Control arm 10%			Control arm 5%	Control arm: 14
Glehen et al[38]	53	54%	40%	CC0 (271/506; 54)	CC0 87%	-	CC0 47%	-	CC0 31%	Males	Unspecified recurrence 73%
				CC1 (106/506; 21)	CC1 79%		CC1 29%		CC1 15%	16.8
				CC2 (129/506; 25)	CC2 38%		CC2 6%		CC2 0%	Females
										21.6
Shen et al[39]	15 (3-85)	75%	-	R0 (13/77; 17)	-	-	R0 69%	-	R0 55%	R0 N/R	Unspecified recurrence 68%
				R1 (24/77; 31)			R1 19%		R1 19%	R1 17.8
				R2a (11/77; 14)			R2a 28%		R2a 14%	R2a 12.7
				R2b (9/77; 12)			R2b 0%		R2b 0%	R2b 4.1
				R2c (20/77; 26)			R2c 6%		R2c 0%	R2c 5.0
Cavaliere et al[40]	16	72%	-	CC0 (102/120; 85)	-	-	Overall	-	-	19	-
				CC1 (9/120; 7)			25.8%
				CC2-3 (9/120; 7)			CC0
							33.5%
Kianmanesh et al[41]	-	70%	75%	-	-	72%	-	44%		38.4	-
Gusani et al[42]	35.9 (19-57.7)	-	-	-	78%	37%	37%	-	-	15.2	-
Verwaal et al[26]	96 (72-115)	-	-	R1 (22/54; 41)	R1 95%	R1 80%	R1 58%	R1 52%	R1 45%	CRS + HIPEC	-
				R2a (23/54; 43)	R2a 65%	R2a 20%	R2a 10%	R2a 10%	R2a 10%	22.2
				R2b (9/54; 17)	R2b 22%	R2b 12%	R2b 0%	R2c 0%	R2c 0%	Systemic CT
										12.6
Yan[17]	14 (1-56)	-	-	CC0 (41/50; 82)	CC0 85%	-	CC0 62%	-	-	CC0 37	Unspecified recurrence 34%
				CC1-3 (9/50; 8)	CC1-3 51%		CC1-3 0%			CC1-3 14
Elias et al[54]	95.7	-	-	-	-	CRS + HIPEC	-	-	CRS + HIPEC	CRS + HIPEC	-
						81%			51%	62.7
						Systemic CT			Systemic CT	Systemic CT
						65%			13%	23.9
Varban et al[43]	14.6	-	-	-	-	HM 43.3%	-	HM 14.4%	-	HM 23	-
						No HM 36.8%		No HM 17.4%		No HM 15.8
Vaira et al[44]	-	55%	-	CC0 (29/40; 73)	CC0 88%	-	-	-	-	Overall: 43	-
				CC2 (11/40; 27)	CC2 42%					CC0: 24
										CC2: 9.7
Glehen et al[45]	-	-	-	-	81%	58%	39%	34%	28%	-	-
Franko et al[55]	-	100	-	-	CRS + HIPEC	CRS + HIPEC	CRS + HIPEC	CRS + HIPEC	CRS + HIPEC	CRS + HIPEC	-
					90%	65%	50%	42%	25%	34.7
					Systemic CT	Systemic CT	Systemic CT	Systemic CT	Systemic CT	Systemic CT
					55%	35%	12%	10%	7%	16.8
Quenet et al[46]	48.5	100%	-	CC0 (132/146; 90)	Overall	Overall	Overall	Overall	-	Overall	Unspecified recurrence 70%
				CC1 (12/146; 8)	92%	72%	55%	50%		41
				CC2 (2/146; 2)
Cashin et al[56]	HIPEC	HIPEC	HIPEC	-	HIPEC	HIPEC group	HIPEC group	HIPEC group	-	HIPEC group	-
	38	81%	38%		100%	78%	60%	48%		36.5
	EPIC	EPIC	EPIC		EPIC	EPIC group	EPIC group	EPIC group		EPIC group
	66	44%	38%		80%	48%	25%	17%		23.9
Passot et al[47]	58.5 (1-183)	75%	64.30%	CC0 (93/120; 78)	Overall	Overall	-	-	Overall	Overall	-
				CC1 (11/120; 9)	77%	51%			33%	36.2
				CC2 (16/120; 13)
Hompes et al[48]	22.7 (3.2-55.7)	-	62.50%	CC0 (48/48; 100)	OS 98%	OS 89%	-	-	-	-	-
					DFS 66%	DFS 46%
Cashin et al[57]	49 (0.5-100)	31%	18%	CC0 (97/151; 64)	HIPEC	HIPEC	HIPEC	HIPEC	-	HIPEC	-
				CC1-3 (54/151; 36)	80%	50%	27%	18%		34
					EPIC	EPIC	EPIC	EPIC		EPIC
					5%	-	-	-		25
Klaver et al[49]	10.5 (1-52)	-	-	CC0 (22/24; 92)	Overall	-	-	-	-	Overall	Unspecified recurrence 54%
				CC1 (2/24; 8)	83%					35
Turrini et al[50]	-	-	-	-	100%	-	51%	-	37%	-	-
Haslinger et al[51]	-	-	-	-	-	-	-	-	OS 38%	-	-
									PFS15%
Yonemura et al[52]	-	77%	-	CC0 (108/142; 76)	-	-	-	-	Overall	Overall	-
				CC1 34/142 (24)					23.4%	24.4
									CC0 20%	CC0 25.9
									CC1 9.9%	CC1 8

¹Peritoneal cancer index (PCI) - Calculated by combining lesion size (0-3; 0-no nodules present, 1-nodule(s) ≤ 5 mm diameter, 2-nodule(s) 5-50 mm in diameter, 3-nodule(s) ≥ 50 mm in diameter) with the abdominopelvic regions affected[33];

²Completeness of cytoreduction score (CCRS)[33]; CC0 No visible tumour remaining; CC1 residual tumour deposits < 2.5 mm in diameter; CC2 residual tumour deposits 2.5-25 mm in diameter; CC3 residual tumour deposits > 25 mm in diameter. HIPEC: Hyperthermic intraperitoneal chemotherapy; EPIC: Early post-operative intraperitoneal chemotherapy; CRS: Cytoreductive surgery; CT: Computed tomography.

Table 3 Reported treatment-associated morbidity and mortality following multi-modality therapy for colorectal peritoneal metastase

Ref.	n	Mortality (%)	Overall morbidity (%)	No of bowel anastomoses	Intra-abdominal complications (%)	Extra-abdominal complications (%)
Portilla et al[33]	18	0	No treatment-associated morbidity data provided
Witkamp et al[34]	29	3	38	2 (0-5)	Postoperative bleeding (3)	Grade I-II leucopenia (21)
					Bowel perforation (3)	Grade III leucopenia (31)
					Bladder perforation (3)	Peripheral neuropathy (10)
					Return to theatre (17)	Subclavian vein thrombosis (3)
					Hydronephrosis requiring nephrostomy (7)
					Wound dehiscence (3)
					Prolonged chyle leak (3)
Pilati et al[35]	34	0	35	-	Non-specified complications: Ozols’grade I (53), grade II (9), grade III (1), grade IV (1)	Haematological toxicity (12)
						Pneumonia (12)
Verwaal et al[36]	106	-	No treatment-associated morbidity data provided
Glehen et al[37]	53	4	23	0.4 (0-4)	Return to theatre (4)	-
					Gastrointestinal fistula (8)
Mahteme et al[53]	18	0	61	-	Severe nausea and vomiting (12)	Transient neutropaenia (6)
					Leak from drain (6)
					Catheter-related problems (39)
Glehen et al[38]	506	4%	22.9	-	Re-operation (10.7)	Haematological toxicity (2.4)
					Fistula (8.3)	Systemic sepsis (2)
					Intra-abdominal abscess (1.8)	Cardiorespiratory complications (3.5)
					Urinary fistula (1)
Shen et al[39]	77	12	30	-	Bowel perforation (3)	Haematological toxicity (19)
Cavaliere et al[40]	120	3.3	22.5	-	Perforation (5)
					Anastomotic leak (3.3)
					Infection (3.3)
Kianmanesh et al[41]	43	2.3	39	-	Deep abscess (14)	Pleural effusion (12)
					Intestinal fistula (9)	Renal failure (7)
					Delayed gastric emptying (9)	Superficial wound infection (12)
					Re-operation (4)
Gusani et al[42]	28	0	56.5	-	Re-operation (8)	Systemic sepsis (4)
					Anastomotic leak (8)
					Intra-abdomoninal abscess (4)
					Wound dehiscence (4)
					Enterocutaneous fistula (2)
Verwaal et al[26]	54	-	No treatment-associated morbidity data provided
Yan[17]	50	0	46	-	Small bowel obstruction (12)	Pleural effusion (34)
					Fistula (10)	Pneumonia (4)
					Intra-abdominal abscess (10)
					Perforation (4)
Elias et al[54]	48	-	No treatment-associated morbidity data provided
Varban et al[43]	142	CPM with HM	CPM with HM	-	CPM with HM	CPM with HM
		7.1%	57.1%		Bowel leak (11)	Pneumonia (7)
		CPM with no HM	CPM with no HM		Wound infection (11)	Neutropaenia (7)
		7.7%	40.1%		Pancreatic fistula (11)	DVT (7)
					Ileus (11)	CPM with no HM
					CPM with no HM	Pneumonia (6)
					Bowel leak (5)	Neutropaenia (8)
					Wound infection (5)	AF (3)
					Ileus (5)	Thrombocytopaenia (2)
					Enterocutaneous fistula (1)
Vaira et al[44]	40	2.5	55	0 (17.5)	Fistula (10)	Haematological toxicity (12.5)
				1(55)	Abdominal abscess (7.5)	Pleural effusion (22.5)
				2 (27.5)		Superficial wound infection (12.5)
Glehen et al[45]	523	-	Not specifically provided for patients undergoing procedures for CPM
Franko et al[55]	105	-	No treatment-associated morbidity data provided
Quenet et al[46]	146	4.1	47.2	-	GI fistula (4.8)	-
					Urinary fistula (1.4)
					Abdominal abscess (2.7)
					Reoperation (11.6)
Cashin et al[57]	32	HIPEC group;	HIPEC group;	-	HIPEC group;	HIPEC group;
		6%	37%		Reoperation (12)	CVA (6)
		EPIC group;	EPIC group;		EPIC group;	EPIC group;
		6%	19%		Reoperation (6)	-
Passot et al[47]	120	3.8	21.8	-	Reoperation (13.3)
					Fistula (7.5)
Hompes et al[48]	48	0	52.1	1 (0-6)	Prolonged ileus (23)	Pulmonary (12.5)
					Anastomotic leakage (10.4)	Cardiac (2.1)
					Bleeding (6.3)	Urological (12.5)
					Bowel perforation (2.1)	Haematological (2.5)
					Fistula (2.1)
					Abscess (2.1)
					Reoperation (20.8)
Cashin et al[56]	151	HIPEC group:	HIPEC group:	-	-	-
		4%	41%
		EPIC group:	EPIC group:
		3%	30%
Klaver et al[49]	24	0	62	-	Prolonged ileus (21)	Superficial wound infection (4)
					Intra-abdominal collection requiring drainage (21)	Cardiorespiratory complications (38)
					Fistula (4)	Urological (4)
					Splenic infarction (4)
Turrini et al[50]	26	0	33	-	Fistula (10)	Haematological toxicity (10)
					Delayed gastric emptying (10)
Haslinger et al[51]	38	-	Not specifically provided for patients undergoing procedures for CPM
Yonemura et al[52]	142	0.7	42.9	-	-	-

CPM: Colorectal peritoneal metastase; HM: Hepatic metastasis; HIPEC: Hyperthermic intraperitoneal chemotherapy; EPIC: Early post-operative intraperitoneal chemotherapy.