+Model

ARTICLE IN PRESS
1 Gastroenterología y Hepatología xxx (xxxx) xxx---xxx
2

Gastroenterología y Hepatología
www.elsevier.es/gastroenterologia

REVIEW

3 Management of symptomatic uncomplicated

4 diverticular colon disease: A systematic review of
5 diagnosis and treatment夽
6 David Saavedra-Perez a,∗,1 , Yuhamy Curbelo-Peña a,1 , Jaime Sampson-Davila a ,
7 Sonia Albertos b , Alejandro Serrano a , Luis Ibañez a , Xavier Errando a , Xavier Perez a

8 Q4 a
Q3 Servicio de Cirugía General y Digestiva, Consorci Sanitari Alt Penedes-Garraf, Barcelona, Spain
b
9 Servicio de Digestología, Consorci Sanitari Alt Penedes-Garraf, Barcelona, Spain

10 Received 29 July 2020; accepted 21 December 2020

11 KEYWORDS Abstract Symptomatic uncomplicated diverticular colon disease (SUDCD) is a highly preva-
12 Diverticular disease; lent disease in our setting, which significantly affects the quality of life of patients. Recent
13 Diverticular colon changes in understanding the natural history of this disease and technological and pharmacolog-
14 disease; ical advances have increased the available options for both diagnosis and treatment. However,
15 Uncomplicated consensus regarding the use of these options is scarce and sometimes lacks scientific evidence.
16 diverticular disease; The objective of this systematic review is to clarify the existing scientific evidence and anal-
17 Uncomplicated yse the use of the different diagnostic and therapeutic options for SUDCD, comparing their
18 diverticular colon advantages and disadvantages, to finally suggest a diagnostic---therapeutic algorithm for this
19 disease; pathology and, at the same time, propose new research questions.
20 Diverticulosis; © 2021 Elsevier España, S.L.U. All rights reserved.
Diverticula

21 PALABRAS CLAVE Enfermedad diverticular de colon no complicada sintomática: revisión sistemática

22 Enfermedad del diagnóstico y tratamiento
diverticular;
23
Enfermedad Resumen La enfermedad diverticular de colon (EDC) no complicada sintomática (EDCNCS) es
24
diverticular de colon; una patología con elevada prevalencia en nuestro medio, que afecta de manera importante
25 la calidad de vida de los pacientes que la padecen. Los cambios recientes en la comprensión

夽
Please cite this article as: Saavedra-Perez D, Curbelo-Peña Y, Sampson-Davila J, Albertos S, Serrano A, Ibañez L, et al. Enfer-
medad diverticular de colon no complicada sintomática: revisión sistemática del diagnóstico y tratamiento. Gastroenterol Hepatol. 2021.
https://doi.org/10.1016/j.gastrohep.2020.12.016
∗ Corresponding author.

E-mail address: dsaavedra@csg.cat (D. Saavedra-Perez).

1 Dr David Saavedra-Perez and Dr Yuhamy Curbelo-Peña contributed equally in carrying out this systematic review.

2444-3824/© 2021 Elsevier España, S.L.U. All rights reserved.

 +Model
ARTICLE IN PRESS
D. Saavedra-Perez, Y. Curbelo-Peña, J. Sampson-Davila et al.

26 de la historia natural de esta enfermedad y los avances tecnológicos y farmacológicos han

27 Enfermedad incrementado sustancialmente las opciones disponibles tanto para su diagnóstico, como para el
28 diverticular no tratamiento. Sin embargo, el consenso que existe en cuanto al uso de estas opciones es pobre
29 complicada; y en algunas ocasiones carente de evidencia científica. El objetivo de esta revisión sistemática
30 Enfermedad es esclarecer la evidencia científica existente y fundamentar la utilización de las diferentes
31 diverticular no opciones diagnósticas y terapéuticas en la EDCNCS, comparando las ventajas y desventajas
32 complicada de colon; entre estas, para sugerir finalmente un algoritmo diagnostico-terapéutico para esta patología
33 Diverticulosis; y al mismo tiempo proponer nuevas preguntas de investigación.
34 Divertículos © 2021 Elsevier España, S.L.U. Todos los derechos reservados.

35 Introduction also play a significant role, attested to by the fact that 79

studies of migratory populations found no changes in the 80

36 Diverticular disease of the colon (DDC) can be classified incidence of DD despite these populations adopting new 81

as complicated or uncomplicated depending on its clin- habits.9 Although the pathogenesis of SUDDC is not fully 82
37 Q5
38 ical presentation.1 Despite a lack of significant clinical understood, dysbiosis and microscopic inflammation seem 83

39 complications, uncomplicated DDC may still be symp- to play an important role.10 Moreover, it has been postu- 84

40 tomatic, manifesting as recurrent or chronic mild abdominal lated that it may be related to an interaction between 85

41 pain, abdominal distension, irregular bowel movements colonic microbiota alterations, and immune, enteric nerve 86

42 (alternating episodes of diarrhoea and constipation) and/or and muscular system dysfunction.11 Up to 20% of peo- 87

43 tenesmus, all caused by the presence of diverticula in the ple with diverticula-associated abdominal pain also have 88

44 colon.1 abnormal motor function and a reduced visceral sensitiv- 89

45 Its non-specific symptoms can make it difficult to dis- ity threshold.11 An increase in the number of mast cells in 90

46 tinguish from other conditions, yet it significantly affects all layers of the colon wall can also contribute to the onset 91

47 patients’ quality of life.1 Complicated DDC has been and of pain.12 The results of a cohort study of more than 9116 92

48 continues to be studied based on the complications that patients suggested that a vitamin D (25-OH) deficiency could 93

49 manifest, and the existing literature supports the differ- increase the risk of complicated AD. The risk of AD was found 94

50 ent clinical standards and guidelines. For this reason, this to decrease with levels of 25---30 ng/mL, and to fall yet fur- 95

51 review of the literature will focus specifically on symp- ther with levels in excess of 30 ng/mL.13 In short, although 96

52 tomatic uncomplicated diverticular disease of the colon the pathogenesis of SUDDC is believed to be multifactorial, 97

53 (SUDDC). it is not yet fully understood. As a result, there is no estab- 98

54 The prevalence of SUDDC has risen in Western countries lished consensus on the diagnosis, follow-up or treatment 99

55 over the last 20 years.2---4 In Spain, more than 50% of adults of patients with uncomplicated DDC, which is reflected by 100

56 over the age of 50 have diverticular disease (DD).5 The the wide variety of requested complementary tests, symp- 101

57 prevalence of DD has been shown to increase with age6 , but tomatic treatments prescribed and follow-up seen in clinical 102

58 it is also important to note that incidence among the active practice. 103

59 population (30---60 years of age) is growing. This entails a risk Our objective is to systematically review the litera- 104

60 of complications and may affect the quality of life of these ture to make sense of the existing scientific evidence and 105

61 patients.2---4 In total, 10%---25% of people with DD develop to justify the use of different diagnostic and therapeutic 106

62 complications, such as acute diverticulitis (AD).7 An analy- options in SUDDC by comparing their respective benefits and 107

63 sis conducted by the Nationwide Inpatient Sample (NIS) in drawbacks. Based on the above, a diagnostic---therapeutic 108

64 the United States between 1998 and 2005 (267,000 admis- algorithm for this disease will be drawn up and new working 109

65 sions) revealed that the incidence of AD-related hospital hypotheses and research questions proposed. 110

66 admissions increased primarily in the 18---44 and 45---64 age

67 ranges, but remained stable in the 65---74 and over-75 age
68 groups.2
Methods 111

69 The pathophysiology of DD is progressive and goes

70 through several stages associated with the form of clinical Search strategy 112

71 presentation (symptoms and presence of complications): (a)

72 development of diverticula; (b) generation of symptoms in A systematic review of the literature was conducted in 113

73 uncomplicated DDC; and (c) development of complications, accordance with the PRISMA protocol. The relevant liter- 114

74 such as AD and other associated conditions.8---12 The aeti- ature up to December 2019 was selected from the MEDLINE 115

75 ology of SUDDC is appears to be multifactorial. Lifestyle and Cochrane databases by searching for the keywords that 116

76 is believed to be a key factor in the development of DD included the following MeSH terminology: ‘‘uncomplicated 117

77 and its complications.8 Prospective studies found that a diverticular disease’’ or ‘‘uncomplicated diverticulosis’’, 118

78 low-fibre diet was associated with DD.9 Genetic factors together with the term ‘‘management’’. A parallel search 119

2
+Model
ARTICLE IN PRESS
Gastroenterología y Hepatología xxx (xxxx) xxx---xxx

Table 1 Database search by MeSH terminology used. Q1

MeSH terms MEDLINE Cochrane

[uncomplicated diverticulosis OR
uncomplicated diverticular disease]
AND management
Role of fiber in symptomatic uncomplicated A randomized double-blind
diverticular disease: a systematic review25 placebo-controlled trial of a
multi-strain probiotic in
treatment of symptomatic
uncomplicated diverticular
disease37
Mesalazine for the treatment of symptomatic Intermittent treatment with
uncomplicated diverticular disease of the mesalazine in the prevention
colon and for primary prevention of of diverticulitis recurrence: a
diverticulitis: a systematic review of randomized multicentre pilot
randomized clinical trials34 double-blind
placebo-controlled study of
24-month duration33
Mesalazine for people with diverticular Quality of life in symptomatic
disease: a systematic review of randomized uncomplicated diverticular disease
controlled trials39 and diverticulitis: conservative vs.
The use of probiotics in different phases of operative treatment38
diverticular disease36
Treatment of diverticular disease, targeting
symptoms or underlying mechanisms27
Evidence for dietary fibre modification in the
recovery and prevention of reoccurrence of
acute, uncomplicated diverticulitis: a
systematic literature review29
Diverticular disease: an update on
pathogenesis and management9
Higher serum levels of vitamin D are
associated with reduced risk of diverticulitis13
Alimentary pharmacology and therapeutics
meta-analysis: long-term therapy with
rifaximin in the management of uncomplicated
diverticular disease31
Diagnosis of symptomatic uncomplicated
diverticular disease and the role of rifaximin in
management17
Rifaximin in the management of colonic
diverticular disease30
Rifaximin and diverticular disease: position
paper of the Italian Society of
Gastroenterology (SIGE)24
Diverticular disease in the primary care
setting16
Medical treatment of diverticular disease
antibiotics32
The management of patients with
diverticulosis and diverticular disease in
primary care: an online survey among Italian
general practitioners22
Pathophysiology and therapeutic strategies for
symptomatic uncomplicated diverticular
disease of the colon11
Intestinal ultrasonography in the diagnosis and
management of colonic diverticular disease23
Management of diverticular disease in
Scandinavia18

3
 +Model
ARTICLE IN PRESS
D. Saavedra-Perez, Y. Curbelo-Peña, J. Sampson-Davila et al.

Table 1 (Continued)

MeSH terms MEDLINE Cochrane

Management of patients with diverticulosis and diverticular disease:
consensus statements from the 2nd International Symposium on
Diverticular Disease26
The role of colonoscopy in managing diverticular disease of the colon20
Diverticular disease: evolving concepts in classification, presentation, and
management28
Routine colonoscopy after acute uncomplicated diverticulitis ---- challenging
a putative indication20
Review article: the pathophysiology and medical management of
diverticulosis and diverticular disease of the colon8
Management of diverticular disease15
Efficacy and safety of a new nutraceutical formulation in managing
patients with symptomatic uncomplicated diverticular disease: a
12-month, prospective, pilot study10
Diverticular disease: guidelines of the German Society for
Gastroenterology, Digestive and Metabolic Diseases and the German Society
for General and Visceral Surgery40
Elective colonic resection after acute diverticulitis improves quality of life,
intestinal symptoms and functional outcome: experts’ perspectives and
review of literature41

120 was performed using the Dietary supplements section to Diagnosis 150
121 complete the search in MEDLINE. The complementary key-
122 words used were: ‘‘treatment’’ and ‘‘follow up’’ (Table 1). The most accurate diagnostic tests for DD are colonoscopy 151

(CS) and computed tomographic colonography (CTC). The 152

choice of one over the other depends on patient prefer- 153

123 Selection criteria
ence, age, clinical status and colorectal cancer risk factors. 154

Double-contrast barium enema is only an option if CTC is not 155

124 The inclusion criteria were: studies published between 1 available. 156
125 January 2009 and 8 November 2019, in English or Spanish,
126 in humans, containing at least one of the aforementioned
127 keywords and with a level of evidence between I and IV.14 Colonoscopy 157

128 Duplicates were removed and articles based on data col-

129 lected prior to 2009 were excluded. Both CS and CTC offer all the benefits of a diagnos- 158

130 The results were displayed in tables in accordance with tic---therapeutic test, but CS carries a higher risk of 159

131 their recommendations and level of scientific evidence. complications, such as perforation and haemorrhage.15 Rou- 160

tine CS is not recommended in primary care for patients 161

with a recent history of AD (<1 month).16 CS could be 162

132 Results the option of choice in young patients (≤40 years) with a 163

low prevalence of DD and a greater risk of inflammatory 164

133 The initial search in MEDLINE and the Cochrane library with bowel disease.17 Routine CS is not recommended in Scandi- 165
134 the aforementioned keywords generated 251 potential arti- navia as it is assumed that patients with an episode of AD 166
135 cles (238 in MEDLINE, 4 in Cochrane and 13 in MEDLINE’s have already undergone computerised tomography (CT).18 167
136 Dietary supplements section). After restricting the search According to international clinical guidelines and best prac- 168
137 to virtual libraries and applying the inclusion criteria, 130 tice, CS has until now been considered the diagnostic test 169
138 preliminary articles were sourced (127 in MEDLINE and 3 in of choice after an episode of AD to confirm the diagno- 170
139 Cochrane). sis and rule out malignancy. However, the routine use of 171
140 After manually assessing the full text of these 130 arti- CS after an episode of AD is disputed.19 Although there is 172
141 cles against the inclusion criteria, 30 articles (27 in MEDLINE no conclusive evidence to suggest that patients with DDC 173
142 and 3 in Cochrane) were considered the primary references are at greater risk of cancer, the overlapping character- 174
143 (Fig. 1). istics of diverticulitis and colon cancer have historically 175
144 The 30 articles included two meta-analyses, three multi- made a differential diagnosis extremely difficult. As a result, 176
145 centre, randomised, double-blind, controlled clinical trials, it is only recommended to perform a CS after conserva- 177
146 three analytical, observational prospective studies, two tively treating AD. Despite this, contradictory evidence has 178
147 prospective cohort studies, one retrospective cohort study, been published in recent years that promotes a more selec- 179
148 five systematic reviews, one clinical guideline, two expert tive approach.19 Andrade et al.20 conducted a retrospective 180
149 consensus statements and 11 reviews (Tables 2 and 3). analysis between 2008 and 2013 to determine the rate of 181

4
 +Model
Table 2 Checklist of the selection of relevant reviewed articles as per the PRISMA protocol.
Article Section/topic

Title Abstract Introduction Objectives Methods

Protocol and Inclusion Information Search Data

registry criteria about collection
sources
Role of fiber in symptomatic X X X X X X X X X
uncomplicated diverticular

Gastroenterología y Hepatología xxx (xxxx) xxx---xxx

disease: a systematic review
Mesalazine for the treatment of X X X X X X X X X

ARTICLE IN PRESS
symptomatic uncomplicated
diverticular disease of the colon
and for primary prevention of
diverticulitis
Mesalazine for people with X X X X X X X X X
diverticular disease: a
systematic review of
randomized controlled trials
5

The use of probiotics in different X X X X X X X X X

phases of diverticular disease
A randomized double-blind X X X X X X X X X
placebo-controlled trial of a
multi-strain probiotic in
treatment of symptomatic
uncomplicated diverticular
disease
Treatment of diverticular disease, X X X X X X X X X
targeting symptoms or
underlying mechanisms
Evidence for dietary fibre X X X X X X X X X
modification in the recovery
and prevention of reoccurrence
of acute, uncomplicated
diverticulitis: a systematic
literature review
Diverticular disease: an update on X X X X X X X X X
pathogenesis and management
 +Model
Table 2 (Continued)

Article Section/topic

Title Abstract Introduction Objectives Methods

Protocol and Inclusion Information Search Data

registry criteria about collection
sources
Higher serum levels of vitamin D X X X X X X X X X

D. Saavedra-Perez, Y. Curbelo-Peña, J. Sampson-Davila et al.

are associated with reduced risk
of diverticulitis
Alimentary pharmacology and X X X X X X X X X

ARTICLE IN PRESS
therapeutics meta-analysis:
long-term therapy with
rifaximin in the management of
uncomplicated diverticular
disease
Diagnosis of symptomatic X X X X X X X X X
uncomplicated diverticular
disease and the role of rifaximin
6

in management
Rifaximin in the management of X X X X X X X X X
colonic diverticular disease
Rifaximin and diverticular disease: X X X X X X X X X
position paper of the Italian
Society of Gastroenterology
(SIGE)
Diverticular disease in the primary X X X X X X X X X
care setting
Medical treatment of diverticular X X X X X X X X X
disease: antibiotics
The management of patients with X X X X X X X X X
diverticulosis and diverticular
disease in primary care: an
online survey among Italian
general practitioners
Pathophysiology and therapeutic X X X X X X X X X
strategies for symptomatic
uncomplicated diverticular
disease of the colon
 +Model
Table 2 (Continued)

Article Section/topic

Title Abstract Introduction Objectives Methods

Protocol and Inclusion Information Search Data

registry criteria about collection
sources
Intestinal ultrasonography in the X X X X X X X X X

Gastroenterología y Hepatología xxx (xxxx) xxx---xxx

diagnosis and management of

ARTICLE IN PRESS
colonic diverticular disease
Management of diverticular X X X X X X X X X
disease in Scandinavia
Management of patients with X X X X X X X X X
diverticulosis and diverticular
disease: consensus statements
from the 2nd International
Symposium on Diverticular
7

Disease
The role of colonoscopy in X X X X X X X X X
managing diverticular disease of
the colon
Diverticular disease: evolving X X X X X X X X X
concepts in classification,
presentation, and management
Routine colonoscopy after acute X X X X X X X X X
uncomplicated diverticulitis ----
challenging a putative
indication
Review article: the X X X X X X X X X
pathophysiology and medical
management of diverticulosis
and diverticular disease of the
colon
Management of diverticular X X X X X X X X X
disease
 +Model
Table 2 (Continued)

Article Section/topic

Title Abstract Introduction Objectives Methods

Protocol and Inclusion Information Search Data

registry criteria about collection
sources

D. Saavedra-Perez, Y. Curbelo-Peña, J. Sampson-Davila et al.

Efficacy and safety of a new X X X X X X X X X
nutraceutical formulation in
managing patients with

ARTICLE IN PRESS
symptomatic uncomplicated
diverticular disease: a
12-month, prospective, pilot
study
Diverticular disease: guidelines of X X X X X X X X X
the German Society for
Gastroenterology, Digestive and
Metabolic Diseases and the
8

German Society for General and

Visceral Surgery
Elective colonic resection after X X X X X X X X X
acute diverticulitis improves
quality of life, intestinal
symptoms and functional
outcome: experts’ perspectives
and review of literature
Intermittent treatment with X X X X X X X X X
mesalazine in the prevention of
diverticulitis recurrence: a
randomised multicentre pilot
double-blind placebo-controlled
study of 24-month duration
Quality of life in symptomatic X X X X X X X X X
uncomplicated diverticular
disease and diverticulitis:
conservative vs. operative
treatment
 +Model
Table 3 Description of the articles selected.
Year Title Study design First Article overview Level of
author evidence

Primary objective Therapy Period or

number of
articles in
reviews
1 2013 Intermittent treatment Multicentre, Parente To evaluate the role Mesalazine 24 months 1b
with mesalazine in the controlled, of mesalazine in the 800 mg every
prevention of standardised, prevention of 12 h compared

Gastroenterología y Hepatología xxx (xxxx) xxx---xxx

diverticulitis recurrence: randomised, diverticulitis to a placebo

ARTICLE IN PRESS
a randomised double-blind, recurrence as well as group
multicentre pilot placebo-controlled its effects on
double-blind clinical trial symptoms of DD of
placebo-controlled study the colon
of 24-month duration
2 2017 A randomised Multicentre, Kvasnovsky Hypothesis: 143 adult 3 months 1b
double-blind controlled, probiotics could patients with
placebo-controlled trial standardised, reduce abdominal SUDDC
of a multi-strain double-blind, pain in patients with randomised to
9

probiotic in treatment of placebo-controlled SUDDC receive

symptomatic clinical trial 1 mL/kg/day of
uncomplicated liquid probiotic
diverticular disease (n = 72) or
placebo (n = 71)
per day for 3
months
Supplement of
L. rhamnosus,
E. faecium, L.
acidophilus and
L. plantarum
3 2016 Quality of life in Prospective, Justin Survey including: age, Survey 1 survey: 2b
symptomatic observational number of episodes 2008---2013
uncomplicated study and frequency, diet
diverticular disease and and physical activity
diverticulitis: as well as adaptation
conservative vs. to the GIQLI and
operative treatment DV-QOL
questionnaires
 +Model
Table 3 (Continued)

Year Title Study design First Article overview Level of

author evidence

Primary objective Therapy Period or

number of

D. Saavedra-Perez, Y. Curbelo-Peña, J. Sampson-Davila et al.

articles in
reviews

ARTICLE IN PRESS
4 2017 Role of fiber in Systematic review Carabotti To update evidence Studies of 19 studies 1b
symptomatic on the efficacy of SUDDC patients
uncomplicated fibre to treat SUDDC, treated with
diverticular disease: a in terms of symptom fibre were
systematic review reduction and AD identified in
prevention the PubMed
and Scopus
databases. The
quality of the
10

studies was
evaluated using
the Jadad scale
5 2016 Mesalazine for the Systematic review Picchio To evaluate the role of 6 articles 1a
treatment of of randomised, mesalazine in symptom
symptomatic controlled clinical improvement, particularly
uncomplicated trials SUDDC-related abdominal pain,
diverticular disease of and in the prevention of
the colon and for recurrent episodes of
primary prevention of diverticulitis
diverticulitis
6 2018 Mesalazine for people Systematic review Iannone To evaluate the role 13 clinical 1a
with diverticular of randomised, of mesalazine in trials
disease: a systematic controlled clinical improving SUDDC
review of randomized trials recurrence
controlled trials
 +Model
Table 3 (Continued)

Year Title Study design First Article overview Level of

author evidence

Primary objective Therapy Period or

number of
articles in
reviews
7 2018 The use of probiotics in Systematic review Ojetti To perform a systematic review 13 studies: 3 1b
different phases of on the possible role of double-blind,
diverticular disease probiotics in managing the randomised,

Gastroenterología y Hepatología xxx (xxxx) xxx---xxx

different phases of DD placebo

ARTICLE IN PRESS
controlled
clinical trials 6
randomised
clinical trials 4
non-
randomised
clinical studies
8 2018 Treatment of Review Cuomo To analyse and summarise the 54 articles 3a
diverticular disease, most recent evidence
11

targeting symptoms or pertaining to DD treatment

underlying mechanisms strategy in each of its different
phases: from prevention to
treatment of AD and
recurrences
9 2018 Recovery and prevention Systematic review Dahl To review the evidence and 3 articles 1b
of reoccurrence of propose recommendations for
acute, literature review dietary fibre modifications,
both alone and in combination
with probiotics or antibiotics
10 2017 Diverticular disease: an Review Rezapour To review the 69 articles 3a
update on pathogenesis pathogenesis of DD
and management
11 2014 Higher serum levels of Cohort Maguire Hypothesis: there is a 9116 patients 1993---2012 2a
vitamin D are associated connection between
with reduced risk of pre-AD diagnosis
diverticulitis levels of 25(OH)D and
diverticulitis cases
that will require
hospitalisation
 +Model
Table 3 (Continued)

Year Title Study design First Article overview Level of

author evidence

Primary objective Therapy Period or

number of
articles in
reviews
12 2011 Alimentary Meta-analysis of 4 Bianchi To evaluate the Rifaximin 4 trials: 1a

D. Saavedra-Perez, Y. Curbelo-Peña, J. Sampson-Davila et al.

pharmacology and randomised long-term efficacy of 400 mg every cyclical
therapeutics clinical trials administering fibre 12 h plus fibre rifaximin
meta-analysis: long-term plus rifaximin doses: 1 dose

ARTICLE IN PRESS
therapy with rifaximin in every 12 h for 7
the management of days, the first
uncomplicated week of each
diverticular disease month for 12
months. All
found that it
prevents AD in
patients with
12

DD
13 2017 Diagnosis of symptomatic Review Maconi SUDDC diagnosis 52 articles 3a
uncomplicated and management
diverticular disease and
the role of rifaximin in
management
14 2009 Rifaximin in the Review Latella To review the effectiveness of 84 articles 3a
management of colonic rifaximin plus fibre in managing
diverticular disease SUDDC
15 2017 Rifaximin and Expert consensus Cuomo To review: 104 articles 5
diverticular disease:
position paper of the
Italian Society of
Gastroenterology (SIGE)
Reasons for using rifaximin in DD.
Clinical trial of rifaximin for
treatment of SUDDC and
prevention of diverticulitis.
Safety of rifaximin and possible
adverse effects
 +Model
Table 3 (Continued)

Year Title Study design First Article overview Level of

author evidence

Primary objective Therapy Period or

number of
articles in
reviews
16 2017 Diverticular disease in Review Wensaas To review DD management in 15 articles 3a

Gastroenterología y Hepatología xxx (xxxx) xxx---xxx

the primary care setting the primary care setting

ARTICLE IN PRESS
17 2016 Medical treatment of Review Lué They conclude that cyclical 22 articles 3a
diverticular disease: rifaximin is recommended in
antibiotics secondary prevention, but not
in primary prevention or to
treat AD
18 2016 The management of Prospective, De Surgeons/gastroenterologists 245 2a
patients with observational Bas- in Italy. Surveyed questionnaires
diverticulosis and study tiani over 4 weeks
13

diverticular disease in
primary care: an online
survey among Italian
general practitioners
19 2016 Pathophysiology and Review Scaioli To perform a search on the 95 articles 3a
therapeutic strategies hypothesis of the pathogenesis
for symptomatic of SUDDC and various
uncomplicated pharmacological strategies
diverticular disease of
the colon
20 2016 Intestinal Review Maconi To show the role of ultrasound 20 articles 3a
ultrasonography in the in DD of the colon, particularly
diagnosis and in the context of diverticulitis
management of colonic and SUDDC
diverticular disease
21 2016 Management of Review Schultz To review DD management in 20 articles 3a
diverticular disease in Scandinavia
Scandinavia
 +Model
Table 3 (Continued)

Year Title Study design First Article overview Level of

author evidence

Primary objective Therapy Period or

number of
articles in
reviews
22 2016 Management of patients Expert consensus Tursi To review aspects 41 statements 18 articles 5

D. Saavedra-Perez, Y. Curbelo-Peña, J. Sampson-Davila et al.

with diverticulosis and such as the rated according
diverticular disease: epidemiology, risk to their level of
consensus statements factors, diagnosis and evidence and

ARTICLE IN PRESS
from the 2nd medical and surgical grade of rec-
International Symposium treatment of DD in ommendation
on Diverticular Disease patients with SUDDC
and DDC
23 2015 The role of colonoscopy Review Tursi They conclude that routine FCS 90 articles 3a
in managing diverticular is not recommended in SUDDC
disease of the colon
24 2015 Diverticular disease: Review Mosadeghi To review recent developments 52 articles 3a
evolving concepts in in the pathophysiology of DD
14

classification, and new evidence in its

presentation, and management
management
25 2015 Routine colonoscopy Retrospective Andrade To determine the rate of Of 252 patients 2b
after acute analysis advanced colonic neoplasia (2008---2013),
uncomplicated found by CS, and therefore the only 3.2% had
diverticulitis ---- need for routine CS after colorectal
challenging a putative CT-diagnosed AD cancer.
indication Incidence
similar to the
general
population, so
routine CS not
justified
26 2015 Review article: the Review Tursi To review current DD 134 articles 3a
pathophysiology and treatment strategies
medical management of
diverticulosis and
diverticular disease of
the colon
 +Model
Table 3 (Continued)

Year Title Study design First Article overview Level of

author evidence

Primary objective Therapy Period or

number of
articles in
reviews
27 2015 Management of Review Pfützer To review current DD 150 articles 3a

Gastroenterología y Hepatología xxx (xxxx) xxx---xxx

diverticular disease treatment strategies

ARTICLE IN PRESS
28 2018 Efficacy and safety of a Prospective, Tursi DIVER 100® (a combination of 15 patients 2a
new nutraceutical observational natural ingredients with
formulation in managing study anti-inflammatory properties:
patients with Boswellia serrata, inulin,
symptomatic niacin, cranberry, vitamins B1,
uncomplicated B2, B6 and B12, zinc and folic
diverticular disease: a acid) 2 capsules per day for 10
12-month, prospective, days a month for 12 months
15

pilot study
29 2014 Diverticular disease: Clinical guidelines Kruis To create a clinical guideline 5
guidelines of the German for DD diagnosis and
Society for management
Gastroenterology,
Digestive and Metabolic
Diseases and the German
Society for General and
Visceral Surgery
30 2016 Elective colonic Review Forgione To review the available 3a
resection after acute literature pertaining to the
diverticulitis improves outcomes of scheduled colon
quality of life, intestinal surgery for DD
symptoms and functional
outcome: experts’
perspectives and review
of literature
AD: acute diverticulitis; CS: colonoscopy; CT: Clinical trial; DD: diverticular disease; SUDDC: symptomatic uncomplicated diverticular disease of the colon.
 +Model
ARTICLE IN PRESS
D. Saavedra-Perez, Y. Curbelo-Peña, J. Sampson-Davila et al.

Records identified by database search conducted

on 9 November
Additional records identified from
Databases: MEDLINE and Cochrane
other sources
Data period: 1 January 2009 -
Identification
Dietary supplements in MEDLINE (n = 13)
9 November 2019
Filters: English, Spanish
Limits: human (Search result = 238)

Records after eliminating duplicates: 0

(n = 251)
Search

Records selected: against inclusion and exclusion Records excluded

criteria (n = 251) (n = 121)
Eligibility

Full-text articles excluded,

Full-text articles evaluated with justification (n = 100)
Reasons for exclusion were
for eligibility (n = 130)
as follows:
- 96 concerned the
management of diverticular
disease complications
Studies included in qualitative (not relevant)
Included

systematic review - 2 full content not available.

- 1 inflammatory bowel
(n = 30)
disease
- 1 traveller's diarrhoea
- The last one only provided
the abstract in English,
while the article itself
was written in Dutch

Figure 1 PRISMA flowchart.

182 advanced colonic neoplasia identified by CS and the need to CT has improved diagnostic accuracy and has challenged 198

183 perform a routine CS after an episode of CT-diagnosed AD. Of the requirement for a routine CS after CT-diagnosed AD.20 199

184 the 252 patients included, colorectal cancer was detected Despite this, according to a prospective study conducted in 200

185 by CS in 3.2%. Given that these findings were similar to Italy by a group led by Bastiani et al.22 , CS continues to be 201

186 the prevalence among the general population, it was con- the first diagnostic test requested by most physicians (77%) 202

187 cluded that routine CS after AD should not be recommended (Table 4). 203

188 (Table 4).21

189 Computerised tomography

Abdominal ultrasound 204

190 Given that CTC offers greater diagnostic accuracy, a lower

191 rate of complications and is less invasive than CS, it may A non-inflamed diverticular wall cannot usually be detected 205

192 be the test of choice in elderly and frail patients, and/or by ultrasound. However, the muscularis propria of the wall 206

193 in patients with potential contraindications for CS and of the colon is often found to be hypertrophic, which can 207

194 sedation.17 However, indicating this test is dependent on be a sign of diverticula. A prospective study that used CS 208

195 the availability of high-resolution, multislice, helical CT as the reference standard found that its sensitivity and 209

196 with image reconstruction and, most importantly, radiolo- specificity for detecting uncomplicated colonic diverticulo- 210

197 gists trained to interpret them. The arrival of high-resolution sis were greater than 85% (Table 4).23 211

16
 +Model
ARTICLE IN PRESS
Gastroenterología y Hepatología xxx (xxxx) xxx---xxx

Table 4 Diagnostic tests for SUDDC, publication recommendations ordered by level of scientific evidence.
Level of evidence Scientific journal Recommendation
and type of study
Colonoscopy
Prashant et al., I Ann Surg Selective CS approach
201419
Meta-analysis Q1
h-Index 284
Pfützer et al., III Nat Rev First choice as it is diagnostic and therapeutic. CT as
201515 Gastroenterol alternative test
Hepatol
Review Q1
h-Index 105
Maconi, 201717 III Acta Biomed First choice in patients <40 years of age due to low incidence
of diverticular disease
Review Q3
h-Index 33
Computerised tomography
Andrade et al., III Dig Surg CT currently improves diagnostic accuracy and challenges the
201620 routine use of CS
Retrospective Q1 Routine CS is not recommended in patients who have recently
cohort had a CT for diverticulitis
252 patients h-Index 65 Same incidence of colorectal cancer in these patients as in the
general population
5 years
Wensaas et al., III J Clin Gastroenterol Routine CS is not recommended in patients who have recently
201616 had a CT for diverticulitis
Review Q1
h-Index 151
Schultz et al., III J Clin Gastroenterol Routine CS is not recommended in patients who have recently
201618 had a CT for uncomplicated acute diverticulitis
Review Q1
h-Index 151
Ultrasound
Maconi et al., III J Clin Gastroenterol Sensitivity >85% for detecting uncomplicated colonic
201623 diverticulosis.
Review Q1 Compared to standard CS
h-Index 151

212 Biochemical markers Treatment 224

213 Non-specific markers like C-reactive protein (CRP) and fae- The first-line treatment for DDC should not be 225

214 cal calprotectin (protein produced by neutrophils) increase pharmacological.24 A high-fibre diet is recommended 226

215 in the event of intestinal inflammation. Faecal calprotectin for these patients. Patients who eat a high-fibre diet have a 227

216 significantly increases in inflammatory bowel disease, but it lower risk of DDC-related hospital admission or death. This 228

217 can also increase in symptomatic uncomplicated DD, raising effect is attributed to the high intake of insoluble fibre.25 229

218 the need for a differential diagnosis.17 It is negative in irrita- However, there is no standard treatment for SUDDC. As well 230

219 ble bowel syndrome.17 However, absolute cut-off values for as making changes in hygiene and dietary habits, it can also 231

220 these markers in SUDDC have not yet been established. A be treated in combination with non-absorbable antibiotics, 232

221 prospective study of physicians found that 77% request lab- anti-inflammatories or probiotics.26 Although DDC does not 233

222 oratory tests as part of DDC patient follow-up, but only 14% require a specific therapy, the treatment of SUDDC is based 234

223 include faecal calprotectin.22 on combinations of different options. All of the above

17
 +Model
ARTICLE IN PRESS
D. Saavedra-Perez, Y. Curbelo-Peña, J. Sampson-Davila et al.

Table 5 High-fibre diet and/or diet with fibre supplements in SUDDC, publication recommendations ordered by level of scientific
evidence.
Level of evidence and Scientific journal Article summary Therapy and
type of study dose
Tursi et al., II J Gastrointestin Liver Reduction of all symptoms, DIVER® 100 2
201810 Dis including abdominal pain. capsules/day
for 10
days/month for
12 months
Systematic review of Q2 No adverse effects or
controlled clinical intolerances, in contrast to
trials mesalazine
h-Index 42
Carabotti II Nutrients Patients who eat a
et al., 201725 high-fibre diet are at lower
risk of DDC-related
hospitalisation or death
Systematic review Q1
h-Index 75
Dahl et al., III Nutrients Insufficient evidence.
201829 Supports use of fibre in
SUDDC
Review Q1
h-Index 75
Mosadeghi III Insufficient evidence.
et al., 201528 Supports use of fibre in
SUDDC
Review
Scaioli et al., III Dig Dis Sci No evidence on eating a
2016 11 high-fibre diet in the
treatment of SUDDC
Review Q1
h-Index
113

235 underlines the lack of progress made in terms of primary et al.28 is based on three studies that modified dietary fibre 254

236 prevention, and that, in managing secondary prevention, intake after an episode of uncomplicated diverticulitis and 255

237 there is currently insufficient evidence to endorse a specific that recorded gastrointestinal symptoms and recurrences, 256

238 strategy, considering the healthcare costs of recurrences.27 each without a control group.29 It concluded that evidence 257

in support of a diet high in dietary fibre and/or dietary 258

fibre supplements, for both recurrence prevention and gas- 259

239 Diet trointestinal symptom improvement, was of poor quality. 260

Although there seems to be little consensus on the role that 261

240 A systematic review of 19 manuscripts published in 2017 by a low-fibre diet plays in the development of DDC, increasing 262

241 Carabotti et al.25 provided an update on the effect of fibre fibre intake is nevertheless likely to have some benefit in 263

242 (both dietary and from supplements). Despite seeming to reducing the complications of DDC. That is why the latest 264

243 be beneficial, the role of fibre in SUDDC symptom control guidelines issued by the American Gastroenterological Asso- 265

244 and its effect on recurrences could not be determined due ciation (AGA) on DDC openly recommend high dietary fibre 266

245 to the poor scientific quality of articles and studies pub- intake in patients with a history of AD (Table 5).9 267

246 lished to date.28 A high-fibre diet has been defined as the

247 intake of at least 30 g of fibre per day. However, with regard
248 to fibre supplements, a meta-analysis on the merits of this Antibiotics 268

249 treatment could not be conducted due to the heterogene-

250 ity of the manuscripts reviewed. As such, no specific dosage The rationale for using non-absorbable antibiotics like rifax- 269

251 could be recommended. It was also not possible to recom- imin to treat DDC is that stasis of the luminal contents of 270

252 mend soluble fibre over insoluble fibre, or vice versa, for the the colon can lead to bacterial overgrowth, which can in 271

253 same reasons.25 The recent systematic review by Mosadeghi turn cause chronic low-grade inflammation of the mucosa.30 272

18
 +Model
ARTICLE IN PRESS
Gastroenterología y Hepatología xxx (xxxx) xxx---xxx

Table 6 Use of antibiotics to treat SUDDC, publication recommendations ordered by level of scientific evidence.
Antibiotics Type of study Scientific journal Article summary Therapy and dose
Bianchi et al., I Aliment 64% of patients receiving 400 mg every 12 h
201131 Pharmacol Ther rifaximin + fibre were for one week per
symptom-free after one month for one
year of treatment. year
Meta-analysis Q1 Compared to 34%
treated with fibre alone
h-Index 159
Latella et al., II Expert Rev Rifaximin + fibre 800---1,200 mg/day
200930 Gastroenterol supplements is better for 7 days per
Hepatol than fibre alone month for 12
months
Systematic review Q2
(4 controlled
clinical trials)
h-Index 41
Scaioli et al., III Dig Dis Sci Improves SUDDC Fibre plus
201611 symptoms but does not rifaximin improves
improve diverticulitis SUDDC symptoms
Review Q1
h-Index
113
Cuomo et al., IV Dig Liver Dis Cyclical rifaximin + fibre
201724 prevents diverticulitis
recurrence in patients
with DD
Expert consensus Q2
h-Index 84

273 A meta-analysis of four randomised clinical trials deter- Mesalazine 299

274 mined the efficacy of rifaximin (400 mg twice daily, one

275 week every month, for one year, together with fibre sup- It has been proposed that chronic inflammation in DD is 300
276 plements) in preventing AD in patients with DD of the colon. similar to inflammatory bowel disease (IBD). That is why 301
277 This meta-analysis found that 64% of patients treated with medicines containing 5-aminosalicylic acid (5-ASA), which 302
278 rifaximin and standard fibre supplements exhibited no symp- are commonly used to treat IBD, have been studied in 303
279 toms at one year of follow-up, compared to 34.9% of patients the management of DD. Parente et al.33 published the 304
280 treated with fibre alone.31 Another systematic review of results of a multicentre, randomised, double-blind con- 305
281 the results of four controlled clinical trials also found rifax- trolled clinical trial, which found that the administration 306
282 imin (800---1200 mg/day, 7 days per month for 12 months) of 800 mg twice a day for 24 months to patients with DD 307
283 plus fibre supplements to be more beneficial than the use reduced the recurrence of AD episodes and improved symp- 308
284 of one of these on its own.30 Other literature reviews also tomatic control compared to patients receiving placebo. 309
285 support these findings.32 A recent position paper also recom- The systematic review by Picchio et al.34 reached the 310
286 mended the use of cyclical rifaximin therapy in secondary same conclusion. It included two placebo-controlled tri- 311
287 prevention, but not for primary prevention or for treating als of mesalazine 800 mg administered every 12 h and 312
288 complicated DDC.24 mesalazine 1 g administered every 8 h, respectively, with 313
289 However, the level of evidence pertaining to the superi- both finding improved symptom control and fewer recur- 314
290 ority of non-absorbable antibiotics over dietary fibre or fibre rences. The reviews conducted by Iannone et al.35 and 315
291 supplements is poor. Moreover, both the cost and the efficacy Scaioli et al.11 found that treatment with mesalazine can 316
292 of long-term cyclical non-absorbable antibiotic treatment reduce SUDDC recurrences, but does not prevent episodes 317
293 to prevent AD in all patients with symptoms consistent of AD (Table 7). 318
294 with DD has been questioned.33 A systematic review pub- Some studies suggest that certain patients could benefit 319
295 lished by Maconi17 points to the potential utility of rifaximin, from the administration of rifaximin or mesalazine in com- 320
296 mesalazine, fibre and probiotics, and their possible combi- bination with fibre.28 However, optimal treatment duration 321
297 nations, in treating SUDDC symptoms, but this has not been and the number of doses has not yet been determined, and 322
298 backed up by controlled clinical trials (Table 6).17 evidence is limited to two years of follow-up (Table 7).24 323

19
 +Model
ARTICLE IN PRESS
D. Saavedra-Perez, Y. Curbelo-Peña, J. Sampson-Davila et al.

Table 7 Use of mesalazine to treat SUDDC, publication recommendations ordered by level of scientific evidence.
Authors Level of evidence and Scientific journal Article summary Therapy and dose
type of study
Parente et al., I Int J Color Dis Improves symptom 800 mg every 12 h
201333 control compared to for 24 months
placebo
Multicentre, Q1
randomised,
double-blind clinical
trial
h-Index 81
Pichio et al., II J Clin Gastroenterol Improves symptom 800 mg every 12 h
201634 control compared to or 8 h for 24
placebo months
Systematic review Q1
(controlled clinical
trials)
placebo-controlled
h-Index 102
Iannone et al., II Can J Gastroenterol Better symptom 800---3,000 mg/day
201839 control than with for 4 weeks/year
rifaximin
Systematic review Q1 Reduces SUDDC
recurrence but
does not prevent
episodes of acute
diverticulitis
h-Index
102
Scaioli et al., III Dig Dis Sci Improves SUDDC
201611 symptoms but does
not improve
diverticulitis
Review Q1
h-Index
113

324 Probiotics design and small sample size of most published studies 343

prevent a definitive conclusion on the therapeutic use of 344

325 The main reasons for using probiotics in SUDDC are their probiotics from being reached. In light of the above, large- 345

326 potential anti-inflammatory effects and their capacity to scale, placebo-controlled clinical trials are still required 346

327 improve local immune response. Some reviews suggest that before probiotics can be conclusively recommended for the 347

328 treatment with probiotics is safe and potentially effec- management of DDC (Table 8).11 348

329 tive in managing patients with SUDDC.30 Three studies have

330 investigated the efficacy of Lactobacillus casei (L. casei
331 DG 24 billion/day) in combination with mesalazine in redu- Nutraceutical supplements 349

332 cing abdominal symptoms in patients with DD. They found

333 that the use of probiotics was at least equivalent to the In recent years, nutraceutical supplements have come to be 350

334 use of the anti-inflammatory, and that their administra- accepted as a safer alternative/supplement to conventional 351

335 tion in combination yielded an even greater beneficial therapy. A prospective study demonstrated their efficacy in 352

336 effect.36 A group led by Kvasnovsky et al.37 recently pub- reducing all symptoms, including abdominal pain, the most 353

337 lished a placebo-controlled clinical trial investigating the common and characteristic symptom of the disease. The 354

338 daily administration of probiotics. It found that the use drug used in this study was DIVER® (combination of natural 355

339 of probiotics improved constipation, diarrhoea, mucus dis- ingredients with anti-inflammatory properties: pinaverium 356

340 charge and back pain, but no significant differences in terms bromide, inulin, niacin, cranberry, vitamins B1, B2, B6 and 357

341 of abdominal pain were identified compared to placebo B12, zinc and folic acid). Its international equivalent mar- 358

342 (p = 0.11). A recent review concluded that the deficient keted in Spain is ELDICET® , with a dosage regimen of 2 359

capsules/day for 10 days/month for 12 months. The authors 360

20
 +Model
ARTICLE IN PRESS
Gastroenterología y Hepatología xxx (xxxx) xxx---xxx

Table 8 Use of probiotics to treat SUDDC, publication recommendations ordered by level of scientific evidence.
Authors Level of evidence and Scientific journal Article summary Therapy and dose
type of study
Kvasnovsky I Inflammopharmacology Improves constipation, 3-month follow-up
et al., 201737 diarrhoea, mucus in n = 143 patients
discharge and back pain
in SUDDC versus placebo.
No differences in
abdominal pain
Multicentre, Q2
randomised,
double-blind,
placebo-controlled
clinical trial
h-Index 45
Ojetti et al., II Rev Recent Clin Equivalent to mesalazine Lactobacillus casei
201836 Trials plus beneficial effect in DG 24 billion/day.
combined probiotic and
mesalazine therapy
Systematic review Q3 In combination
(controlled clinical with high-fibre
trials) diet
h-Index 30
Scaioli et al., III Dig Dis Sci No conclusions on the
201611 use of probiotics could
be drawn
Review Q1
h-Index
113

361 proposed that these results were due to the specific anti- complications must be weighed up against the surgical risk 386

362 inflammatory role of this formulation. Furthermore, as no (age, body mass index, comorbidities and specific surgical 387

363 adverse events were reported, they also recommend their complications) as well as the risk of severe complications. 388

364 use in patients with comorbidities or intolerance to other Age should not be considered an indication for a more 389

365 treatments, such as mesalazine.10 This anti-inflammatory aggressive surgical approach. In terms of patients’ quality 390

366 effect could be due to its ingredients. For example, folic of life, Justin et al.38 conducted a 200-patient satisfaction 391

367 acid can help to enhance the activity of regulatory T cells, survey from 2008 to 2013. The quality of life index score 392

368 while vitamin B6 can reduce inflammation both by increas- was slightly higher (1.2%; p = 0.77) in the group treated 393

369 ing the activity of interleukin 10 as well as by promoting surgically for DD recurrence. In total, 92% of surgically- 394

370 the growth of Lactobacilli strains, a species of bacteria that managed patients were satisfied or completely satisfied with 395

371 appears to be effective in controlling SUDDC symptoms.10 the outcome after the operation. However, the difference 396

in quality of life was only slightly higher (and not statisti- 397

cally significant) for the surgical group. Nevertheless, these 398

372 Elective surgery results, together with the high rate of patient satisfaction, 399

could support a surgical indication in patients with recurrent 400

373 It has historically been postulated that, with each addi- episodes of diverticulosis. The duration, but not the sever- 401

374 tional episode of diverticulitis, the probability of recurrent ity, of diverticulitis may be associated with an increased risk 402

375 episodes and the risk of complications increases, while the of recurrence, but this is not an independent risk factor.26 403

376 likelihood of responding to medical treatment decreases. In conclusion, there is insufficient evidence to consider a 404

377 Elective sigmoidectomy should not be based on the num- single risk factor as an independent indication for elective 405

378 ber of AD episodes. Experts recommend that the analysis surgery in DD patients.26 406

379 be based on the personalised study of each case, taking

380 into account the time elapsed between the last episode of
381 diverticulitis and surgery, and prioritising minimally-invasive
382 approaches.26 Each clinical situation should be carefully Follow-up 407

383 evaluated (persistence of symptoms and signs of compli-

384 cation, age, degree of diverticulitis, immunosuppressed In terms of patient follow-up, no consensus has been reached 408

385 patients, etc.). The severity of any DD-related symptoms or on how these patients should be managed. However, based 409

21
 +Model
ARTICLE IN PRESS
D. Saavedra-Perez, Y. Curbelo-Peña, J. Sampson-Davila et al.

Treatment of SUDDC

First visit: confirm the diagnosis

Patient with compatible signs and symptoms +/- positive faecal calprotectin

Recent episode
of diverticulitis?

Abdominal CT with
FCS NO YES IV contrast n

Confirmed diagnosis
of SUDDC

Initial treatment with oral fibre

+/- oral fibre supplements No change: discharge and follow-up
in primary care centre
1 month NO
Add fibre: oral rifaximin (400 mg/
Persistence of symptoms? 12 h for first 7 days of each
month for 12 months)
YES

NO 6 months
Follow-up every 6 months until 12
months of rifaximin have been completed Persistence of symptoms?

YES
Persistence of symptoms?
What is the predominant
symptom?
Discharge from YES
general surgery and
routine primary care
follow-up
NO Diarrhoea, mucus discharge Abdominal pain
and/or constipation
Multidisciplinary
assessment DIVER®/
Probiotics (Lactobacillus
for surgery ELDICET®
casei DG 24 billion/day) 2 capsules/day
YES +/- mesalazine (800 mg/12 h for 10 days/month
for 24 months) for 12 months

Persistence of symptoms?

Figure 2 Treatment diagram. At each visit, remember the warning signs for referral to the emergency room to prevent
complications.
The international equivalent of DIVER® marketed in Spain is ELDICET® .

410 on the results of our study, we propose a treatment algo- should be scheduled throughout this period to monitor 422

411 rithm that can be summarised as follows (Fig. 2): the treatment. Treatment should be combined with fibre 423

throughout this period. 424

• In cases where symptoms are not well controlled, partic- 425

412 • During the first visit with a SUDDC patient, a CS or CTC (if
ularly abdominal pain, nutraceuticals should be included 426
413 available) should be requested/performed to confirm the
as an alternative to conventional treatment. 427
diagnosis (see ‘‘Diagnosis’’ section). The differential diag-
•
414
In patients with predominantly diarrhoea- and/or 428
415 nosis with other diseases should be complemented by CRP
constipation-like symptoms, consider probi- 429
and faecal calprotectin. It is also important to prescribe
otics ± mesalazine.
416
430
a high-fibre diet or daily oral fibre supplements.
•
417
At each visit, remember the warning signs for referral to 431
418 • Outpatient follow-up to determine the need to add a new
the emergency room to prevent complications. 432
treatment, such as rifaximin, as per the patient’s clini-
•
419
In terms of elective surgery for patients with SUDDC, no 433
420 cal course, prescribing cyclical therapy for the first seven
consensus has yet been reached. The decision should be 434
421 days of each month for 12 months. A six-monthly visit

22
 +Model
ARTICLE IN PRESS
Gastroenterología y Hepatología xxx (xxxx) xxx---xxx

435 assessed by the treating physicians taking into account the uncomplicated diverticular disease of the colon. Dig Dis Sci. 488

436 risk of complications and/or the impact on quality of life 2016;61:673---83. 489

437 in each case. We recommend a multidisciplinary approach 12. Tursi A. New physiopathological and therapeutic approaches 490

438 (general surgeon and gastroenterologists). to diverticular disease: an update. Expert Opin Pharmacother. 491
2014;15:1005---17. 492
13. Maguire LH, Song M, Strate LE, Giovannucci EL, Chan AT. Higher 493
439 12:29 pm
serum levels of vitamin D are associated with reduced risk of 494
diverticulitis. Clin Gastroenterol Hepatol. 2014;11:1---11. 495
440 Conclusions 14. Developing NICE guidelines: the manual; 2014. Available 496
from: https://www.nice.org.uk/process/pmg20/resources/ 497

441 SUDDC treatment is based on a multidisciplinary approach developing-nice-guidelines-the-manual-pdf-72286708700869 498

15. Pfützer RH, Kruis W. Management of diverticular disease. Nat 499
442 and long-term patient follow up (years), taking into
Rev Gastroenterol Hepatol. 2015;12:629---38. 500
443 account the different available strategies: fibre, rifaximin,
16. Wensaas K, Hungin AP. Diverticular disease in the primary care 501
444 mesalazine and nutraceuticals. Surgery should be assessed setting. J Clin Gastroenterol. 2016;50:86---8. 502
445 on a case-by-case basis. Recommendations for SUDDC mana- 17. Maconi G. Diagnosis of symptomatic uncomplicated diverticular 503
446 gement may change with the publication of new evidence of disease and the role of Rifaximin in management. Acta Biomed. 504
447 higher scientific quality, which is much needed to improve 2017;88:25---32. 505

448 clinical practice. New prospective and randomised studies 18. Schultz JK, Yaqub S, Øresland T. Management of diverticular 506

449 are required to standardise combined treatment regimens. disease in Scandinavia. J Clin Gastroenterol. 2016;50:50---2. 507
19. Prashant V, Eglinton T, Hider P, Frizelle F. Systematic review 508
and meta-analysis of the role of routine colonic evaluation after 509
450 Authors radiologically confirmed. Ann Surg. 2014;259:263---72. 510
20. Andrade P, Ribeiro A, Ramalho R, Lopes S, Macedo G. Routine 511
451 All the authors participated in the writing this article and colonoscopy after acute uncomplicated diverticulitis ---- chal- 512

452 agree to its submission. lenging a putative indication. Dig Surg. 2016;34:197---202. 513
21. Tursi A. The role of colonoscopy in managing diverticular disease 514
of the colon. J Gastrointestin Liver Dis. 2015;24:85---93. 515
453 Conflicts of interest 22. De Bastiani R, Sanna G, Fracasso P, Urso MD, Benedetto E, Tursi 516
A. The management of patients with diverticulosis and diver- 517
454 The authors declare that they have no conflicts of interest. ticular disease in primary care an online survey among Italian 518
general pratictioners. J Clin Gastroenterol. 2016;50:89---92. 519

References 23. Maconi G, Carmagnola S, Guzowski T. Intestinal ultrasonogra- 520

455
phy in the diagnosis and management of colonic diverticular 521
disease. J Clin Gastroenterol. 2016;50:20---2. 522
456 1. Salem TA, Molloy RG, O’Dwyer PJ. Prospective five-year 24. Cuomo R, Barbara G, Annibale B. Rifaximin and diver- 523
457 follow-up study of patients with symptomatic uncomplicated ticular disease: position paper of the Italian Society of 524
458 diverticular disease. Dis Colon Rectum. 2007;50:1460---4. Gastroenterology (SIGE). Dig Liver Dis. 2017;49:595---603, 525
459 2. Etzioni DA, Mack TA, Beart RW, Kaiser AM. Diverticulitis in the http://dx.doi.org/10.1016/j.dld.2017.01.164. 526
460 United States: 1998---2005 changing patterns of disease and 25. Carabotti M, Annibale B, Severi C, Lahner E. Role of fiber in 527
461 treatment. Ann Surg. 2009;249:210---7. symptomatic uncomplicated diverticular disease: a systematic 528
462 3. Warner E, Crighton EJ, Moineddin R, Mamdani M, Upshur R. review. Nutrients. 2017;9:1---14. 529
463 Fourteen-year study of hospital admissions for diverticular dis- 26. Tursi A, Picchio M, Elisei W, di Mario F, Scarpignato C, Brandi- 530
464 ease in Ontario. Can J Gastroenterol. 2007;21:97---9. marte G. Management of patients with diverticulosis and 531
465 4. Kang JY, Hoare J, Tinto A, Subramanian S, Ellis C, Majeed diverticular disease consensus statements from the 2nd Interna- 532
466 A, et al. Diverticular disease of the colon ---- on the rise : a tional Symposium on Diverticular Disease. J Clin Gastroenterol. 533
467 study of hospital admissions in England between 1989/1990 and 2016;50:S101---7. 534
468 1999/2000. Aliment Pharmacol Ther. 2003;17:1189---95. 27. Cuomo R, Cargiolli M, Cassarano S, Carabotti M, Annibale 535
469 5. San Juan Acosta M, Jiménez Contreras S. Enfermedad Divertic- B. Treatment of diverticular disease, targeting symptoms or 536
470 ular del Colon. Concepto y Causas. Diverticulos y Enfermedad underlying mechanisms. Curr Opin Pharmacol. 2018;43:124---31, 537
471 Diverticular. Fundación Española del Aparato Digestivo; 2016. http://dx.doi.org/10.1016/j.coph.2018.09.006. 538
472 6. Everhart JE, Ruhl CE. Burden of digestive diseases in the United 28. Mosadeghi S, Bhuket T, Stollman N. Diverticular disease: evolv- 539
473 States. Part II: lower gastrointestinal diseases. Gastroenterol- ing concepts in classification, presentation, and management, 540
474 ogy. 2009;136:741---54. 31; 2015. p. 50---5. 541
475 7. Heise CP. Epidemiology and pathogenesis of diverticular dis- 29. Dahl C, Crichton M, Jenkins J, Nucera R, Mahoney S, Marx W, 542
476 ease. J Gastrointest Surg. 2008;12:1309---11. et al. Evidence for dietary fibre modification in the recovery 543
477 8. Tursi A, Papa A, Danese S. Review article: the pathophysiol- and prevention of reoccurrence of acute, uncomplicated diver- 544
478 ogy and medical management of diverticulosis and diverticular ticulitis: a systematic literature review. Nutrients. 2018;10: 545
479 disease of the colon. Aliment Pharmacol Ther. 2015;42:664---84. 1---18. 546
480 9. Rezapour M, Ali S, Stollman N. Divrticular disease: an update on 30. Latella G, Scarpignato C. Rifaximin in the management of 547
481 pathogenesis and management. Gut Liver. 2018;12:125---32. colonic diverticular disease. Expert Rev Gastroenterol Hepatol. 548
482 10. Tursi A, di Mario F, Brandimarte G, Elisei W, Picchio M. Effi- 2009;3:585---98. 549
483 cacy and safety of a new nutraceutical formulation in managing 31. Bianchi M, Festa V, Moretti A, Ciaco A, Mangone M, Tornatore 550
484 patients with symptomatic uncomplicated diverticular disease: V, et al. Alimentary pharmacology and therapeutics meta- 551
485 a 12-month, prospective, pilot study. J Gastrointestin Liver Dis. analysis: long-term therapy with rifaximin in the management 552
486 2018;27:201---5. of uncomplicated diverticular disease. Aliment Pharmacol Ther. 553
487 11. Scaioli E, Colecchia A, Marasco G, Schiumerini R, Festi D. 2011;33:902---10. 554
Pathophysiology and therapeutic strategies for symptomatic

23
 +Model
ARTICLE IN PRESS
D. Saavedra-Perez, Y. Curbelo-Peña, J. Sampson-Davila et al.

555 32. Lué A, Laredo V, Lanas A. Medical treatment of diverticular a multi-strain probiotic in treatment of symptomatic uncom- 575
556 disease antibiotics. J Clin Gastroenterol. 2016;50:57---9. Q7 plicated diverticular disease. Inflammopharmacology. 2017, 576
557 33. Parente F, Bargiggia S, Prada A, Bortoli A, Giacosa A, Germanà http://dx.doi.org/10.1007/s10787-017-0363-y. 577
558 B, et al. Intermittent treatment with mesalazine in the preven- 38. Justin V, Nagele-Moser D, Uranues S. Quality of life in symp- 578
559 tion of diverticulitis recurrence: a randomized multicentre pilot tomatic uncomplicated diverticular disease and diverticulitis: 579
560 double-blind placebo-controlled study of 24-month duration. conservative vs. operative treatment. Surg Endosc Other Interv 580
561 Int J Color Dis. 2013;28:1423---31. Tech. 2016;30:3---6. 581
562 34. Picchio M, Elisei W, Brandimarte G, Di Mario F, Malfertheiner 39. Iannone A, Ruospo M, Wong G, Barone M, Principi M, di Leo A, 582
563 P, Scarpignato C, et al. Mesalazine for the treatment of symp- et al. Mesalazine for people with diverticular disease: a system- 583
564 tomatic uncomplicated diverticular disease of the colon and atic review of randomized controlled trials. Can J Gastroenterol 584
565 for primary prevention of diverticulitis a systematic review of Hepatol. 2018, http://dx.doi.org/10.1155/2018/5437135. 585
566 randomized clinical trials. J Clin Gastroenterol. 2016;50:64---9. 40. Kruis W, Germer C-T, Ludger L. Diverticular disease: guide- 586
567 35. Iannone A, Ruospo M, Wong G, Barone M, Principi M, di Leo A, lines of the German Society for Gastroenterology, Digestive and 587
568 et al. Mesalazine for people with diverticular disease: a system- Metabolic Diseases and the German Society for General and 588
569 atic review of randomized controlled trials. Can J Gastroenterol Visceral Surgery. Digestion. 2014;90:190---207. 589
570 Hepatol. 2018;2018:1---12. 41. Forgione A, Guraya SY. Elective colonic resection after acute 590
571 36. Ojetti V, Petruzziello C, Cardone S, Saviano L, Migneco A, diverticulitis improves quality of life, intestinal symptoms and 591
572 Gabrielli M, et al. The use of probiotics in different phases of functional outcome: experts’ perspectives and review of liter- 592
573 diverticular disease. Rev Recent Clin Trials. 2018;13:89---96. ature. Updat Surg. 2016;68:53---8. 593
574 37. Kvasnovsky CL, Bjarnason I, Nora A, Sherwood RA, Papagrigo-
riadis S. A randomized double-blind placebo-controlled trial of

24