Therapeutic improvement of colonic anastomotic healing under complicated conditions: A systematic review

Table 1 Studies on therapeutic compounds in ischemic models

Ref.	Compound	Time of administration	Species	Sex	Sample size1	Dosage	Route	Test	Test day	Effect2
Yagci et al[33]	HBOT	Preoperative	Rat	M	20			BPR	5	NS
		Postoperative			20					↑ 23
		Preoperative and postoperative			20					↑ 37
Hamzaoğlu et al[31]	HBOT	Postoperative	Rat	M	16			BPR	4	↑ 32
Guzel et al[35]	HBOT	Postoperative	Rat	F	20			BPR	4	↑ 50
	HBOT + β-1,3-glucan				20	203	IP			↑ 67
	β-1,3-glucan				20	203	IP			↑ 50
Kemik et al[36]	HBOT	Postoperative	Rat	F	20			BPR	4	↑ 80
	HBOT + LMWH				20	14	SC			↑ 67
	LMWH				20	14	SC			NS
Adas et al[21]	VEGF-A plasmid	Intraoperative	Rat	M	40	0.0013	LO	BPR	4	↑ 16
	FGF-2 plasmid					0.0013				↑ 14
	VEGF-A + FGF-2 plasmids					0.0013 + 0.0013				↑ 38
Saribeyoğlu et al[38]	PDGF-BB	Intraoperative	Rat	M	20	1253	LO	BPR	4	↑ 8
Yarimkaya et al[32]	GH	Preoperative and postoperative	Rat	M	28	15	SC	BPR	3/7	↑ 87/↑ 32
	Nandrolone	Preoperative			28	24	IM			↑ 55/NS
Tasdelen et al[39]	Leptin	Postoperative	Rat	N/A	20	0.0014	IP	BPR	7	↑ 27
Parra-Membrives et al[34]	Pentoxifylline	Postoperative	Rat	M, F	38	504	IP	BPR/BST	8	↑ 74/↑ 81
Sümer et al[40]	Pentoxifylline	Postoperative	Rat	M, F	20	504	IP	BPR	5	NS
	Vinpocetine				20	14				NS
Karatepe et al[41]	Adrenomedullin	Postoperative	Rat	F	32	0.0023	SC	BPR	3/7	↑ 5/↑ 20
Cetinkaya et al[43]	Bostentan	Postoperative	Rat	F	20	3.54	IP	BPR	6	↑ 46
Garcia et al[22]	Allopurinol	Preoperative and postoperative	Rat	M	20	504	PO	BPR	4	↑ 74
Adas et al[44]	MSCs	Intraoperative	Rat	M	40	0.56	LO	BPR	4/7	↑ 110/↑ 86
Adas et al[45]	MSCs	Postoperative	Rat	M	40	0.56	iv	BPR	4/7	↑ 42/NS
Dinc et al[46]	GM-CSF	Intraoperative	Rat	M	72	0.0504	LO	BPR	3/7	↑ 30/↑ 26
Ikeda et al[47]	Prostacyclin analogue (OP-41483)	Intraoperative and postoperative	Dog	M, F	107	0.000044	iv	AL	3	NS
					188					↓ 100
					129					NS
Cohen et al[48]	Neomycin + erythromycin	Preoperative	Rat	N/A	12	203	PO	AL	7	↓ 83
	Clindamycin + gentamicin				12	154 + 24	iv			NS
Karataş et al[49]	Amelogenin	Intraoperative	Rat	M	16	N/A	LO	BPR	4	↑ 25
Irkorucu et al[50]	Sildenafil	Postoperative	Rat	M	27	104/204	PO	BPR	4	NS/NS
Coneely et al[51]	Compound 48/80	Preoperative	Rat	M	20	14	iv	BPR	4	NS

¹Total number of animals;

²↑% increase (P < 0.05) or ↓% decrease (P < 0.05) vs controls;

³mg;

⁴mg/kg;

⁵IU/kg;

⁶mL;

⁷Slight ischemia;

⁸Moderate ischemia;

⁹Severe ischemia. AL: Anastomotic leakage; BPR: Bursting pressure; BST: Breaking strength; F: Female; FGF-2: Fibroblast growth factor-2; GH: Growth hormone; GM-CSF: Granulocyte macrophage-colony stimulating factor; HBOT: Hyperbaric oxygen therapy; IP: Intraperitoneal; iv: Intravenous; LMWH: Low molecular weight heparin; LO: Local; M: Male; MSCs: Bone marrow derived mesenchymal stem cells; N/A: Data not available; NS: Not statistically significant; PDGF-BB: Platelet-derived growth factor-BB; PO: Per os; SC: Subcutaneous; VEGF-A: Vascular endothelial growth factor-A.

Table 2 Studies on therapeutic compounds in ischemia/reperfusion injury models

Ref.	Compound	Time of administration	Species	Sex	Sample size1	Dosage	Route	Test	Test day	Effect2
Tekin et al[56]	ATIII	Preoperative and postoperative	Rat	M	16	2503	iv	BPR	6	↑ 74
Unal et al[57]	Ethyl pyruvate	Preoperative	Rat	M	24	504	IP	BPR	5	↑ 63
		Preoperative and postoperative								↑ 69
Kabali et al[53]	NAC	Preoperative	Rat	F	30	3004	PO/IP	BPR	7	↑ 25/↑ 37
Aydin et al[55]	Tempol	Preoperative and postoperative	Rat	M	20	304	iv	BPR	5	↑ 6
Teke et al[58]	Activated protein C	Preoperative and postoperative	Rat	M	24	0.14	iv	BPR	7	↑ 7
Teke et al[59]	Caffeic acid phenethyl ester	Preoperative and postoperative	Rat	M	24	0.00284	iv + IP	BPR	7	↑ 7
Teke et al[54]	Pyrrolidine dithiocarbamate	Preoperative and postoperative	Rat	M	20	1004	iv	BPR	6	↑ 6
Celik et al[52]	Montelukast	Preoperative and postoperative	Rat	M	24	104	IP	BPR	5	↑ 36

¹Total number of animals;

²↑% increase (P < 0.05) vs controls;

³IU/kg;

⁴mg/kg; ATIII: Antithrombin III; BPR: Bursting pressure; F: Female; IP: Intraperitoneal; iv: Intravenous; M: Male; NAC: N-acetyl cysteine; PO: Per os.

Table 3 Studies on therapeutic compounds in obstructive colon and obstructive jaundice models

Ref.	Compound	Time of administration	Species	Sex	Sample size1	Dosage	Route	Test	Test day	Effect2
Erbil et al[23]	PI	Preoperative	Rat	M	144	103	Lavage	BPR	3/6	↑ 44/↑ 42
	L-NAME					0.13				↓ 26/↓ 28
Aguilar-Nascimento et al[60]	PI	Preoperative	Rat	M	40	103	Lavage	BPR	3/6	NS/↑ 41
								BST		NS/↑ 28
Faruquzzaman et al[63]	EPO	Postoperative	Guinea pig	M	20	5004	SC	BPR	7	↑ 15
Moran et al[61]	EPO	Postoperative	Rat	M	20	5004	SC	BPR	7	↑ 12
Galanopoulos et al[62]	Iloprost	Postoperative	Rat	M	40	0.0025	IP	BPR	4/8	↑ 115/↑ 74
								AL		NS/NS
6Gulcelik et al[17]	GM-CSF	Intraoperative	Rat	M	44	0.0505	LO	BPR	3	↑ 24

¹Total number of animals;

²↑% increase (P < 0.05) or ↓% decrease (P < 0.05) vs controls;

³%-solution;

⁴IU/kg;

⁵mg/kg;

⁶Model of obstructive jaundice. AL: Anastomotic leakage; BPR: Bursting pressure; BST: Breaking strength; EPO: Erythropoietin; GM-CSF: Granulocyte macrophage-colony stimulating factor; IP: Intraperitoneal; L-NAME: NG-nitro-L-arginine methyl ester; LO: Local; M: Male; NS: Not statistically significant; PI: Povidone iodine; SC: Subcutaneous.

Table 4 Studies on therapeutic compounds in models of peritonitis

Ref.	Compound	Time of administration	Species	Sex	Sample size1	Dosage	Route	Test	Test day	Effect2
Ayten et al[67]	Sildenafil	Postoperative	Rat	F	14	83	IP	BPR	7	↑ 43
Diller et al[74]	ATIII	Intraoperative	Mouse	M	60	2504	iv	BPR	2	↑ 34
									4	NS
									7	↑ 38
Gunerhan et al[72]	UFH	Postoperative	Rat	M	45	503	SC	BPR	7	↑ 12
	LMWH					1.53				↑ 19
Onur et al[76]	Ethyl pyruvate	Postoperative	Rat	N/A	20	503	IP	BPR	7	↑ 51
Aytekin et al[68]	Tempol	Preoperative and postoperative	Rat	M	20	303	iv	BPR	6	↑ 10
Ergin et al[75]	G-CSF	Preoperative and postoperative	Rat	M	20	0.0503	SC	BPR	4	↑ 26
	Levamisole				20	53	PO			NS
Teke et al[69]	Activated protein C	Preoperative and postoperative	Rat	M	24	0.13	iv	BPR	7	↑ 9
Teke et al[70]	Caffeic acid phenethyl ester	Preoperative and postoperative	Rat	M	24	0.00283	IP	BPR	7	↑ 9
Teke et al[71]	Pyrrolidine dithiocarbamate	Preoperative and postoperative	Rat	M	20	1003	iv	BPR	6	↑ 7
Akkuş et al[73]	Taurolidine	Intraoperative	Rat	F	40	0.55	Lavage	BPR	3/7	↑ 26/↑ 12
Bicalho et al[78]	Chlorhexidine	Intraoperative	Rat	M	16	0.055	Lavage	BPR	7	NS
Wang et al[79]	Hydroxyethyl starch	Preoperative and postoperative	Rat	M	32	7.56	iv	BPR	5	NS
						156				↑ 9
						306				↓ 5
Wang et al[80]	Hydroxyethyl starch	Preoperative and postoperative	Rat	M	20	156	iv	BPR	5	↑ 9
Sucullu et al[81]	HBOT	Postoperative	Rat	M,F	32			BPR	3/7	↑ 186/↑ 74
Rocha et al[82]	HBOT	Postoperative	Rat	M	30			BST	5	NS
Vaneerdeweg et al[83]	Gentamicin	Intraoperative	Rat	M	30	2.67/123	LO/IM	BPR	4	NS/NS

¹Total number of animals;

²↑% increase (P < 0.05) or ↓% decrease (P < 0.05) vs controls;

³mg/kg;

⁴IU/kg;

⁵%-solution;

⁶mL/kg;

⁷mg. ATIII: Antithrombin III; BPR: Bursting pressure; BST: Breaking strength; F: Female; G-CSF: Granulocyte-colony stimulating factor; HBOT: Hyperbaric oxygen therapy; IM: Intramuscular; IP: Intraperitoneal; iv: Intravenous; LMWH: Low molecular weight heparin; LO: Local; M: Male; N/A: Data not available; NS: Not statistically significant; PO: Per os; SC: Subcutaneous; UFH: Unfractionated heparin.

Table 5 Studies on therapeutic compounds in chemotherapeutic model

Ref.	Compound	Time of administration	Species	Sex	Sample size1	Dosage	Route	Test	Test day	Effect2
Cetinkaya et al[91]	GM-CSF	Postoperative	Rat	N/A	54	0.0503	LO	BPR	3	↑ 26
Erdem et al[86]	GM-CSF	Postoperative	Rat	N/A	30	0.0503	LO	BPR	3	↑ 98
de Waard et al[87]	GM-CSF	Postoperative	Rat	M	31	0.0053	IP	BPR/BST	7	↓ 35/NS
	Interleukin-2					42 × 106	SC			NS/NS
Bostanoğlu et al[88]	Iloprost	Postoperative	Rat	M	38	0.0023	N/A	BPR	3/7	↑ 63/NS
Vasiliadis et al[90]	Iloprost	Postoperative	Rat	F	34	0.0023	IP	BPR	5/8	↑ 44/NS
								AL		↓ 30/↓ 30
Zacharakis et al[89]	IGF-1	Postoperative	Rat	M	32	23	IP	BPR/AL	7	↑ 53/NS
Erenoğlu et al[84]	HBOT	Postoperative	Rat	M	20			BPR	7	↑ 26
5Yildiz et al[85]	HBOT	Postoperative	Rat	F	24			BPR	5	NS

¹Total number of animals;

²↑% increase (P < 0.05) or ↓% decrease (P < 0.05) vs controls;

³mg/kg;

⁴IU/kg;

⁵Chemoradiotherapy model. AL: Anastomotic leakage; BPR: Bursting pressure; BST: Breaking strength; F: Female; GM-CSF: Granulocyte macrophage-colony stimulating factor; HBOT: Hyperbaric oxygen therapy; IGF-1: Insulin-like growth factor-1; IP: Intraperitoneal; LO: Local; M: Male; N/A: Data not available; NS: Not statistically significant; SC: Subcutaneous.

Table 6 Studies on therapeutic compounds in models of radiotherapy

Ref.	Compound	Time of administration	Species	Sex	Sample size1	Dosage	Route	Test	Test day	Effect2
Demir et al[96]	NAC	Preoperative and postoperative	Rat	M	24	3005	PO/IP	BPR	4	↑ 126/↑ 182
Ozdemir et al[94]	Amifostine	Preoperative	Rat	F	20	2005	IP	BPR	5	↑ 16
Carroll et al[93]	Ribose-cysteine3	Preoperative	Rat	M	72	20005	IP	BPR	7	↑ 50
	Ribose-cysteine4	Preoperative				50005	IP			N/A
	Ribose-cysteine3 + glutamine3	Preoperative and postoperative				20005 + 36	IP + PO			NS
	Amifostine3	Preoperative				2505	IP			↑ 46
	Amifostine4	Preoperative				2505	IP			NS
	MgCl23 + ATP3	Preoperative				107 + 507	iv			↑ 67
Rowe et al[97]	Ribose-cysteine	Preoperative	Pig	M	12	10005	iv	BPR	9/11	NS
Değer et al[27]	Pycnogenol	Preoperative	Rat	M	40	2005	PO	BPR	3/7	↑ 19/↑ 38
Ozel Turkcu et al[95]	EPO	Preoperative and postoperative	Rat	M	16	5008	IM	BPR	N/A	NS

¹Total number of animals;

²↑% increase (P < 0.05) vs controls;

³40 GY;

⁴70 GY;

⁵mg/kg;

⁶%-solution;

⁷g/kg;

⁸IU/kg. ATP: Adenosine triphosphate; BPR: Bursting pressure; EPO: Erythropoietin; F: Female; IM: Intramuscular; IP: Intraperitoneal; iv: Intravenous; M: Male; NAC: N-acetyl cysteine; N/A: Data not available; NS: Not statistically significant; PO: Per os.