Operative management of acute diverticulitis in immunosuppressed compared to immunocompetent patients: A systematic review

Table 1 MEDLINE-OVID search strategy

1 Colonic diverticulitis.mp. or diverticulitis, colonic/

2 Colonic diverticulosis.mp. or diverticulosis, colonic/

3 Colonic diverticulum.mp. or diverticulum, colon/

4 Colonic diverticula.mp.

5 (Colon diverticulosis or colon diverticulitis or colon diverticula or colon diverticulum).mp.

6 Diverticulitis/su [Surgery]

7 (Diverticulosis or diverticulitis).mp.

8 1 or 2 or 3 or 4 or 5 or 6 or 7

9 HIV infections/or acquired immunodeficiency syndrome/or sexually transmitted diseases, viral/

10 Immunologic deficiency syndromes/

11 HIV infections.ab,ti.

12 “HIV/aids”.ab,ti.

13 Aids positive.ab,ti.

14 HIV positive.ab,ti.

15 Chemoprevention/or chemoradiotherapy/or chemotherapy, adjuvant/

16 Chemotherapy.mp.

17 Neutropenia/or Neutropenia.mp. or febrile neutropenia/or chemotherapy-induced febrile neutropenia/

18 Corticosteroid.ab,ti.

19 Steroid.ab,ti.

20 Radiation oncology/mt (methods)

21 Radiation/ae, th (Adverse Effects, Therapy)

22 Exp organ transplantation

23 Organ transplanta.ab,ti.

24 [(Heart or Kidney or Liver or Pancreas or Lung) adj transplanta].ab,ti.

25 Immunodeficienta.ab,ti.

26 (Solid adj3 transplant).ab,ti.

27 Lymphocyte depletion.mp. or lymphocyte depletion/

28 Graft enhancement, immunologic/

29 Graft enhancement.mp.

30. Desensitization, immunologic/

31 Hyposensitization therapy.mp.

32 (Anti-Rejection Therapa or Antirejection Therapa).mp.

33 Immunosuppressa.mp. or immunosuppressive agents/

34 Immunocompromised host.mp. or immunocompromised host

35 Immunocompromised.mp.

36 Exp immune tolerance/

37 Immunosuppression.mp. or Immunosuppression/

38 6-mercaptopurine.mp. or 6-Mercaptopurine/

39 Methotrexate.mp. or methotrexate

40 Methylprednisolone/or methyl-prednisolone.mp./

41 Basiliximab.mp.

42 Mycophenolate.mp.

43 Mycophenolic acid.mp. or mycophenolic acid

44 Copaxone.mp.

45 Exp prednisolone/

46 Cyclophosphamide/or ifosfamide/

47 Cyclophosphamide.mp.

48 Prednisone.mp. or prednisone/

49 Cyclosporine.mp. or cyclosporine/

50 Remicade.mp.

51 Daclizumab.mp.

52 Sirolimus.mp. or Sirolimus/

53 Dexamethasone.mp. or exp Dexamethasone/

54 Tacrolimus.mp. or tacrolimus/

55 Interferons.ab,ti.

56 humira.mp.

57 Imuran.mp. or azathioprine/

58 CellCept.mp.

59 Infliximab.mp.

60. Etanercept.mp.

61 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 30 or 31 or 32 or 33 or 34 or 35 or 36 or 37 or 38 or 39 or 40 or 41 or 42 or 43 or 44 or 45 or 46 or 47 or 48 or 49 or 50 or 51 or 52 or 53 or 54 or 55 or 56 or 57 or 58 or 59 or 60

62 Postoperative complications/or surgical wound dehiscence/or

surgical wound infection/

63 Perioperativeoutcomea.mp.

64 Prognosisa/or treatment outcome/or treatment failure/

65 Peri-operative outcomes.mp.

66 Perioperative period.mp. or exp perioperative period/

67 Postoperative outcomes.mp.

68 Sepsis.mp. or exp sepsis/

69 Septicemiaa.mp.

70 Pyemiaa.mp.

71 Exp patient acuity/

72 Failure to rescue.mp.

73 (Surgical adj2 infectiona).mp.

74 (Surgery adj5 infectiona).mp.

75 Anastomosis, surgical/or anastomosis leak.mp

76 Length of stay.mp. or “length of stay”/

77 Mortality/or “cause of death”/or survival rate/

78 (Mortality or surgery).ab,ti.

79 Colectomy.mp. or colectomy/

80 (Hartmann's or Hartmanns or Hartmann).ab,ti.

81 Laparotomy.mp. or laparotomy/

82 Bowel resection.mp.

83 Colostomy.mp. or colostomy/

84 Ileostomy.mp. or ileostomy/

85 Anterior resection.mp.

86 Colon resection.mp.

87 Recurrencea/

88 Recurrence.ab,ti.

89 Acute kidney injury.mp. or acute kidney injury/

90 Acute renal failure.mp.

91 Complications.ab,ti.

92 Implications.ab,ti.

93 62 or 63 or 64 or 65 or 66 or 67 or 68 or 69 or 70 or 71 or 72 or 73 or 74 or 75 or 76 or 77 or 78 or 79 or 80 or 81 or 82 or 83 or 84 or 85 or 86 or 87 or 88 or 89 or 90 or 91 or 92

94 Immunocompetent.mp.

95 Immunocompetence.mp. or immunocompetence/

96 (Immune adj competenca).mp.

97 (Immuno adj competenca).mp.

98 Immunocompetency.ab,ti.

99 (Nonimmunocompromised or nonimmunocompromized).ab,ti.

100 (Non adj immunocompromi?ed).ab,ti.

101 (Immunologica adj Competence).ab,ti.

102 (Immune adj system).ab,ti.

103 (Control or comparison or compare or groups or normal or different or difference).ab,ti.

104 Comparative studies.ab,pt,ti.

105 94 or 95 or 96 or 97 or 98 or 99 or 100 or 101 or 102 or 103 or 104

106 8 and 61 and 93 and 105

107 (Case Reports or Practice Guideline or Guideline or case study).pt.

108 Case series.ab,ti.

109 Case report.ab,ti.

110 107 or 108 or 109

111 106 not 110

^aOrgan transplant in the search strategy refers to solid organ transplantation which include; the pancreas, lung, heart, liver and kidney; pt: Publication type; ab: Abstract; ti: Title.

Table 2 Characteristics of the included studies

Ref.	Year	Country	Study design	No. of patients1		Total n	Follow-up period (mo)
				IMS	IMC
Canter et al[9]	1970	United States	Retrospective	11	38	49	NR
Perkins et al[10]	1984	United States	Retrospective	10	31	41	NR
Tyau et al[11]	1991	United States	Retrospective	23	55	78	NR
Hesterberg et al[15]	1994	Germany	Retrospective	12	80	92	NR
Qasabian et al[16]	2004	Australia	Retrospective	8	16	24	Mean 57 (SD NR)
Reshef et al[1]	2012	United States	Case control	51	51	102	NR
Biondo et al[13]	2012	Spain	Prospective	61	254	315	Mean 81.62 ± 67.62 SD
Halabi et al[12]	2013	United States	Retrospective	1249	753517	754766	NR
Golda et al[14]	2014	Spain	Retrospective	53	63	116	NR
Total				1478	754105	755583

¹Number of patients managed operatively. NR: Not reported; SD: Standard deviation; IMS: Immunosuppressed; IMC: Immunocompetent.

Table 3 Definition of immunosuppression

Ref.	Definition
Canter et al[9]	Long-term steroid use
Perkins et al[10]	Renal transplant
	Glomerulonephritis on steroids
	Lymphoma
	Long-term steroid use
Tyau et al[11]	Long-term steroid use
	Concurrent extracolonic malignant neoplasm/chemotherapy
	Malnutrition
	Uremia
Hesterberg et al[15]	Long-term steroid use
	Concurrent extracolonic malignant neoplasm/chemotherapy
	Azathioprine
	Iatrogenic leucopenia
Qasabian et al[16]	Heart and lung transplant
Biondo et al[13]	Concurrent history of immunosuppressant
	Solid organ transplant
	Concurrent extracolonic malignant neoplasm
	Emphysema
	Concurrent extracolonic malignant neoplasm/chemotherapy
	Collagen vascular disease, arthritis
	Chronic pulmonary fibrosis
	Congenital or acquired immunodeficiency syndromes
	End stage renal failure (hemodialysis)
Reshef et al[1]	Liver transplant
	Heart transplant
	Lung transplant
	Renal transplant
Halabi et al[12]	Renal transplant
Golda et al[14]	Concurrent history of immunosuppressant
	Long-term steroid use
	Concurrent extracolonic malignant neoplasm
	End stage renal failure (hemodialysis, peridialysis)

Table 4 Age at episode of acute diverticulitis

Ref.	IMS (yr)	IMC (yr)
Canter et al[9]	60	58
Perkins et al[10]	NR (37-83)	64 (37-93)
Tyau et al[11]	64 ± 12.9 SD	59.1 ± 14.7
Hesterberg et al[15]	63 (38-90)	NR
Qasabian et al[16]	54 (41-69)	66 (45-91)
Reshef et al[1]	55.9 ± 9.3 SD	62.3 ± 11.3 SD
Biondo et al[13]	68.4 ± 11.7 SD	61 ± 15.1 SD
Halabi et al[12]	59 (51-67)	65 (55-77)
Golda et al[14]	68.5 ± 10.6 SD	59.7 ± 16.4 SD

NR: Not reported; SD: Standard deviation; IMS: Immunosuppressed; IMC: Immunocompetent.

Table 5 Choice of operations

Ref.	Emergency										Elective
	Immune status(IMS/IMC)	Total n	Stoma anddrainage	HP	RPA	RPA with DLS	Subtotal colectomywith anastomosis	Subtotal colectomywith ileostomy	Drainageonly	Unknown	Total n	RPA	RPA with DLS	Unknown
Canter et al[9]	IMS	9	8						12	0	2	2		0
	IMC	22	NR						NR	22	16	NR		16
Perkins et al[10]	IMS	101	5	3	0				1	0
	IMC	31	11	7	12				1	0
Tyau et al[11]	IMS	23	4	17	1	1			0	0
	IMC	55	8	27	14	3			3	0
Hesterberg et al[15]	IMS	8	1	5	1	1				0	4	4		0
	IMC	36	NR	NR	NR	NR				36	44	NR		44
Qasabian et al[16]	IMS	8	6			2				0
	IMC	16	13			3
Reshef et al[1]	IMS	37	1	28	0	8				0	14	5	9	0
	IMC	37	0	28	1	8				0	14	NR	NR	14
Biondo et al[13]	IMS	57		37		11	3	1		5	4
	IMC	1822		56		97	5	3		21	72
Halabi et al[12]	IMS
	IMC
Golda et al[14]	IMS	53		42	2	9				0
	IMC	63		15	39	9				0
Total n	IMS	205	25	132	4	32	3	1	2	5	20	11	9	0
	IMC	442	32	133	66	120	5	3	4	79	132	NR	NR	67

¹One intra-operative death;

²With subsequent right hemicolectomy. HP: Hartmann procedure; RPA: Resection and primary anastomosis; RPA with DLS: Resection and primary anastomosis with diverting loop stoma; NR: Not reported; IMS: Immunosuppressed; IMC: Immunocompetent.

Table 6 Morbidity and mortality in elective setting

Ref.	Immune status(IMS/IMC)	Total n	Mortalityn (%)	Morbidityn (%)	Anastomoticleak n (%)	Abdominal collection/Abscess n (%)	Wound infectionn (%)	Sepsisn (%)	Reoperationn (%)	Post op bleedn (%)	Post op ileusn (%)	Readmissionn (%)
Canter et al[9]	IMS	2	0
	IMC	16	NR
Hesterberg et al[15]	IMS	4	0
	IMC	44	0
Qasabian et al[16]
1Reshef et al[1]	IMS	14	0	4 (29)	1 (7)	0	3 (20)		1 (7)	0	1 (7)	4 (24)
	IMC	14	0	4 (29)	1 (7)	1 (7)	2 (13)		2 (14)	1 (7)	1 (7)	2 (14)
2Biondo et al[13]	IMS	4	0	4 (100)	1 (25)		1 (25)		2 (50)
	IMC	72	0	4 (5)	0		3 (4)		1 (1)
Halabi et al[12]	IMS	471	3 (0.6)
	IMC	404623	4856 (1)

¹Some patients had two or more complications;

²3 morbidities of which 5 are not reported. NR: Not reported; IMS: Immunosuppressed; IMC: Immunocompetent.

Table 7 Morbidity and mortality in the emergency setting

Ref.	Immunestatus(IMS/IMC)	Totaln	Mortalityn (%)	Morbidityn (%)2	Anastomoticleak n (%)	Abdominalcollection/Abscess n (%)	Woundinfectionn (%)	Sepsisn (%)	Post-opileusn (%)	Post-opbleedn (%)	Renalfailuren (%)	Reoperationn (%)	Arrythmias/cardiacdecompensationn (%)	Pulmonaryinfection/Insufficient n (%)	Othersn (%)
Canter et al[9]	IMS	9	3 (33)	3 (33)	3 (33)
	IMC	22	NR	NR	0
1Perkins et al[10]	IMS	10	1 (10)	7 (70)		3 (30)	4 (40)	5 (50)
	IMC	31	0	NR		2 (7)	5 (16)	1 (3)
Tyau et al[11]	IMS	23	9 (39)	15 (65)
	IMC	55	1 (2)	13 (24)
Hesterberg et al[15]	IMS	8	1 (13)
	IMC	36	NR
Qasabian et al[16]
Reshef et al[1]	IMS	37	7 (19)	19 (51)	1 (3)	2 (5)	3 (8)		3 (8)	4 (11)			1 (3)	2 (5)	DVT; IMS, 3 IMC, 2 UTI; IMS, 2 Readmission; IMS, 5 IMC, 4
	IMC	37	0	9 (24)	1 (3)	3 (8)	5 (14)		2 (5)	1 (3)			0	2 (5)
Biondo et al[13]	IMS	57	19 (33)
	IMC	182	29 (16)
Halabi et al[12]	IMS	778	57 (0.7)
	IMC	348894	17130 (5)
Golda et al[14]	IMS	53	14 (26)	42 (79)	1 (2)	11 (21)	22 (42)	13 (25)	10 (19)	0	7 (13)	16 (30)	9 (17)	11 (21)
	IMC	63	4 (6)	40 (64)	3 (5)	4 (6)	30 (48)	7 (11)	8 (13)	1 (2)3	5 (8)	5 (8)	2 (3)	7 (11)
Total	IMS	975	111/ 975 (11)	86/132 (65)	5	16	29	18	13	4	7	16	10	13
	IMC	349320	17164/ 349320 (5)	62/155 (40)	4	9	40	8	10	2	5	5	2	9

¹Some patients had 2 or more complications;

²5 studies reported overall morbidity;

³Gastrointestinal bleed. DVT: Deep vein thrombosis; UTI: Urinary tract infection; NR: Not reported; IMS: Immunosuppressed; IMC: Immunocompetent.

Table 8 Length of hospital stay in the emergency and elective settings

Ref.	Immune Status(IMS/IMC)	LOS in ERsetting (d)	LOS in electivesetting (d)
Reshef et al[1]	IMS	19.3	9.6
	IMC	9.4	6.5
Biondo et al[13]	IMS	NR	19.3 ± 13.6 SD
	IMC	NR	9.4 ± 6.8 SD
Golda et al[14]	IMS	24.8 ± 25.2 SD
	IMC	15.5 ± 10.5

SD: Standard deviation; NR: Not reported; LOS: Length of hospital stay; IMS: Immunosuppressed; IMC: Immunocompetent; ER: Emergency.