Scandinavian Journal of Gastroenterology

ISSN: 0036-5521 (Print) 1502-7708 (Online) Journal homepage: http://www.tandfonline.com/loi/igas20

Acute colonic diverticulitis: modern understanding

of pathomechanisms, risk factors, disease burden
and severity
Kjetil Sreide, Marja A. Boermeester, David J. Humes & George C. Velmahos
To cite this article: Kjetil Sreide, Marja A. Boermeester, David J. Humes & George C.
Velmahos (2016): Acute colonic diverticulitis: modern understanding of pathomechanisms,
risk factors, disease burden and severity, Scandinavian Journal of Gastroenterology, DOI:
10.1080/00365521.2016.1218536
To link to this article: http://dx.doi.org/10.1080/00365521.2016.1218536

Published online: 19 Aug 2016.

Submit your article to this journal

View related articles

View Crossmark data

Full Terms & Conditions of access and use can be found at

http://www.tandfonline.com/action/journalInformation?journalCode=igas20
Download by: [Cornell University Library]

Date: 19 August 2016, At: 06:04

SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, 2016

http://dx.doi.org/10.1080/00365521.2016.1218536

REVIEW

Acute colonic diverticulitis: modern understanding of pathomechanisms, risk

factors, disease burden and severity
Kjetil Sreidea,b, Marja A. Boermeesterc, David J. Humesd and George C. Velmahose,f
a
Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway; bDepartment of Clinical Medicine, University of
Bergen, Bergen, Norway; cDepartment of Surgery, Academic Medical Center, Amsterdam, the Netherlands; dDivision of Epidemiology and
Public Health, School of Community Health Sciences, University of Nottingham, Nottingham, UK; eDivision of Trauma Emergency Surgery
and Surgical Critical Care, Massachusetts General Hospital, Boston, MA, USA; fHarvard Medical School, Boston, MA, USA

ABSTRACT

ARTICLE HISTORY

Introduction: Conservative, non-antibiotic and non-surgical management of acute diverticulitis is currently being investigated. To better inform clinical decisions, better understanding of disease mechanisms, disease burden and severity is needed.
Methods: Literature search of risk factors, pathophysiology, epidemiology and disease burden/severity
reported over the last decade.
Results: Acute diverticulitis is a common disease and has a high disease burden. Incidence of hospital
admissions is reported around 71 per 100,000 population, with reported increase in several subpopulations over the last decades. The incidence is likely to increase further with the aging populations. Risk
factors for left-sided acute diverticulitis include dietary, anthropometric and lifestyle factors. Disease
mechanisms are still poorly understood, but a distinction between inflammation and infection is
emerging. The integrative and complex role of the gut microbiota has become an interesting factor for
both understanding the disease as well as a potential target for intervention using probiotics. Mild,
self-limiting events are increasingly reported from studies of successful non-antibiotic management in
a considerable number of cases. Risk markers of progression to or presence of severe, complicated disease are needed for better disease stratification. Current risk stratification by clinical, imaging or endoscopic means is imperfect and needs validation. Long-term results from minimal-invasive and
comparative surgical trials may better help inform clinicians and patients.
Conclusions: Over- and under-treatment as well as over- and under-diagnosis of severity is likely to
continue in clinical practice due to lack of reliable, robust and universal severity and classification systems. Better understanding of pathophysiology is needed.

Received 18 March 2016

Revised 19 July 2016
Accepted 22 July 2016
Published online 17 August
2016

Introduction
Acute colonic diverticulitis is a common disease condition in
the Western world. Understanding of the mechanisms and
risk factors leading to development of diverticulae and subsequent inflammation has been poorly understood in the
past and, consequently, management strategies may have
suffered from inadequate appreciation of underlying pathogenesis leading to over- and under-treatment using
both antibiotics, preventive measures, as well as surgical
approaches.[13] This is reflected in a number of deviations
in coexisting expert recommendations, or societal and
national guidelines issued in the past.[49] However, emerging evidence has challenged past understanding of acute
diverticulitis, which has led to a number of challenges of previous management strategies, including less use of antibiotics
for uncomplicated disease, the role of preventive measures
and debate over surgical approaches for complicated
cases.[3,1012] Still, management appears to vary considerably between regions.[1316] In order to arrive at more uni-

CONTACT Kjetil Sreide

ksoreide@mac.com

KEYWORDS

Diverticulitis; colonicdisorders; emergency;

prevention; pathophysiology; epidemiology;
severity; classification

form treatment approaches, a better understanding of

the disease is needed. Thus, the aim of this review is to
search and evaluate the contemporary evidence and present
updated knowledge on the epidemiology, pathogenesis and
risk factors and its potential implication on prevention and
management.

Methods
A literature search of the English literature over the past decade (January 2006June 2016) for studies related to epidemiology, pathogenesis, risk factors, prevention and surveillance.
Key search words used included epidemiology, risk factors,
pathomechanism, pathogenesis, severity, classification
coupled with Booolean word AND for Acute diverticulitis.
Papers from the past 5 years were prioritized, as were studies
of higher evidence level (i.e., randomized trials). Systematic
reviews, meta-analysis and updated guidelines were
searched, where available.

Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway

2016 Informa UK Limited, trading as Taylor & Francis Group

K. SREIDE ET AL.

Results
Pathogenesis of disease
The prevalence of diverticulosis of the colon increases with
age and is found in approximately 10% of those aged
50 years rising to 50% in those over 80 years. Change in the
extracellular matrix and altered collagen structure with age
partly explains this pattern. Diverticulae typically occur in the
colonic wall where the capillary mesenteric arteries perforate
the tissue, thus rendering a potential weakness in the wall
(Figure 1).
Diverticulae occur more frequently in the sigmoid as
opposed to the right colon, indicating a relation to both
intraluminal pressure and intraluminal content. No clear genetic defect has been identified in those with diverticulitis.
The estimated liability due to genetic factors was reported at
between 40% and 50% in two Scandinavian studies of siblings.[17,18] The reported risk was greater in twins with the
greatest risk in monozygotic twins.
Low-grade inflammation as propagated in patients with
obesity may also play a role in the pathogenesis of acute
diverticulitis.[19] More recently the integrative and complex

role of the gut microbiota has become an interesting factor

for both understanding the disease as well as a potential target for intervention.[20] However, current evidence on probiotics in this regard is scant at best and does not support a
clear benefit as a treatment option.[21]
Also, diverticulitis patients have a higher diversity of fecal
microbiota than controls from a mixed population, with the
phylum Proteobacteria defining the difference.[22] The analysis of intestinal microbiota may offer novel ways to diagnose diverticulitis. Interestingly, the interplay between diet,
activity and obesity may all be associated with a change in
gut microbiota and linked to an inflammatory response in
the colon (Figure 1). The long line of putative mechanisms
have been reviewed in more detail elsewhere.[20,23,24] Of
notice, chronic diverticular symptoms, such as abdominal
pain, bloating, tenesmus and diarrhea, may be caused by
low-level mucosal inflammation similar to that occurring in
chronic idiopathic inflammatory bowel disease (IBD; Crohns
disease or ulcerative colitis), for which correlates have been
demonstrated on biopsies. Chronic inflammation is related to
relatively increased levels of proinflammatory cytokines as
measured in blood. The cytokine increase may be triggered,

Figure 1. Illustration of the multifactorial influence on diverticulitis development and risk of progression during a life-time perspective.

SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY

at least in part, by altered peridiverticular microflora. For

example, Bifidobacterium longum and Bifidobacterium animalis
are found to be significantly more frequent and more abundant in patients with diverticulitis than in patients with colon
cancer or IBD.[20]
Further understanding of the progression and severity of
acute diverticulitis is important for stratification of therapy.
Most bouts of diverticulitis are self-limiting with up to 95%
of cases of uncomplicated diverticulitis not requiring hospital
admission.[2527] The challenge is to differentiate which
patients need aggressive initial treatment from those who
would respond to conservative measures alone. While clinical
experience may suggest that a majority of acute diverticulitis
episodes may be simple, self-limiting inflammatory episodes
without need for treatment other than supportive
care,[28,29] the distinction to truly infectious disease and disease that progresses with risk of bowel-wall disruption and
life-threatening peritonitis and sepsis is currently not possible. Thus, need for better biomarkers of risk and severity
measures, as well as knowledge of antibiotics and their role
in disease control is needed.

increase in incidence in those aged 1844 years (82%) and

4574 years (36%).[38] A further study of the NIS dataset
from 2002 to 2007 reported a 9.5% annual increase in the
emergency admission rate for acute diverticulitis.[36]
These studies all confirmed an increase in disease burden
associated with acute diverticulitis and this pattern of
increased burden can also be seen from hospital discharge
data in England for diverticular disease.[39,40] Possible
explanations for this increase may be systematic biases in
the data coding of the administrative databases used however no systematic changes were reported over this time
period. The other possibility is a change in the diagnostic
tests utilized over this period with more mild cases being
hospitalized for treatment however this should have resulted
in changes in diagnostic sensitivity across all groups and not
the differential rates of increase that were reported by age
group. The disease burden associated with acute diverticular
disease appears to be increasing. An aging population and
changes in diet and other factors may be related to the
increase in incidence and prevalence. However, further studies are required to determine which factors may underlie this
increase in disease burden.

Epidemiology of diverticular disease

The underlying structural abnormality of the colon (diverticulosis) is common in Western populations, predominately
affecting the left side of the colon which is in contrast to
that seen in Asian populations, where a predominantly rightsided distribution occurs.[3034] The true incidence of acute
diverticulitis is unknown, as studies reporting rates of acute
diverticulitis have focused solely on those patients admitted
to secondary care despite substantial numbers of patients
being treated in primary care.[3538]
Three large population-based studies have reported on
the occurrence of acute diverticulitis using the Nationwide
Inpatient Sample (NIS) from the United States.[35,36,38] The
first of these studies used population census data to report
population-based incidence rates and found an increase in
incidence of hospital admissions coded for acute diverticulitis
from 0.59 to 0.71 per 1000 population over the period
19982005.[38] This represented a 26% increase in age
adjusted admissions from 1998 to 2005 with the greatest

Risk factors
Risk factors for left-sided acute diverticulitis include dietary,
anthropometric and lifestyle factors. Consumption of a vegetarian diet was associated with a 31% (relative risk [RR]: 0.69,
95% confidence interval [CI]: 0.550.86) lower risk of admission to hospital or death from diverticular disease compared
to meat eaters in a large cohort study.[41] Increasing dietary
fiber intake has been shown in two large cohort studies to
be associated with a decreased risk of developing symptomatic diverticular disease (Table 1).[42,43]
Patients with known diverticular disease were previously
advised not to consume nuts, popcorn and corn. However a
recent report from the American Health Care Professionals
Follow Study found no relationship between consumption of
corn, nuts or popcorn with the development of
diverticulitis.[44]
A near 3-fold increase in RR of acute diverticulitis was
reported following a diagnosis of alcoholism in a Danish

Table 1. Summary of risk factors for symptomatic diverticular disease.

Outcome

Exposure

Comparison

Adjusted
RR (95% CI)

Diet
Crowe et al. [42]
Aldoori et al. [43]

Diverticular disease requiring hospital admission

Symptomatic diverticular disease

Dietary fiber intake 5/g day

Highest quintile of dietary
fiber intake

Lowest quintile of intake

690,075
43,881

0.86 (0.840.88)
0.63 (0.440.91)

Smoking
Hjern et al. [47]
Aldoori et al. [46]

Symptomatic diverticular disease

Symptomatic diverticular disease

Current past smoking

Current smoking

Nonsmokers
Nonsmokers

35,809
47,678

1.32 (1.111.57)
1.25 (0.752.09)

BMI
Hjern et al. [49]
Strate et al. [48]

Symptomatic diverticular disease

Diverticulitis

BMI >30 kg/m2

BMI >30 kg/m2

BMI 2024.99 kg/m2

BMI <21 kg/m2

36,592
47,228

1.33 (1.031.72)
1.78 (1.082.94)

Physical activity
Hjern et al. [49]
Strate et al. [50]

Symptomatic diverticular disease

Diverticulitis

<30 min/day
>57.4 MET-h/week

>30 min/day
<8.2 MET-h/week

31,456
47,228

1.53 (1.281.82)
0.75 (0.580.95)

MET-h/week denotes metabolic equivalent hours per week.

K. SREIDE ET AL.

cohort of female and male alcoholic patients (RR: 2.9, 95% CI:
2.14.0 and RR: 2.0 95% CI: 1.52.6).[45] In moderate drinkers
this relationship appears to be weaker with a 1.4-fold
increase in risk in those drinking >30 g of alcohol per day
compared to nondrinkers (RR: 1.36, 95% CI: 0.941.97).[46]
Current and past smoking was associated with a moderate
increase in the risk of developing symptomatic diverticular
disease compared to nonsmokers (Table 1).[46,47]
An increased risk of acute diverticulitis has been reported
in obese men (body mass index [BMI] > 30 kg/m2, RR: 1.78,
95% CI: 1.082.94 compared to BMI <21 kg/m2).[48] A similarly increased risk of diverticular disease and complicated
disease has been reported amongst obese women (BMI
>30 kg/m2, RR: 1.33, 95% CI: 1.031.72 compared to BMI
2024.99 kg/m2).[49] Two large cohort studies have reported
that increased physical activity is associated with a reduced
risk of acute diverticulitis (Table 1).[49,50]
A recent casecontrol study from Sweden found no evidence that that statins affected the development of symptomatic diverticular disease in general (adjusted OR: 1.00,
95% CI: 0.941.06).[51] However, in the same study, current
statin use was associated with a reduced risk of emergency
surgery for diverticular disease (adjusted OR: 0.70, 95% CI:
0.550.89).

Classification of disease
Historically, the stages of diverticulitis have been classified
using the Hinchey classification,[52] for which Classes III
and IV would require immediate surgery with resection of
the diseased bowel and a stoma (Hartmanns procedure).[53,54] This approach has been challenged as imaging
studies have revealed that even patients with generalized
peritonitis and free air may recover by less invasive measures, such as intravenous antibiotics, percutaneous drainage
and potentially laparoscopic lavage with appropriately
placed drains.[1] There are currently no imaging studies,
biomarkers or clinical risk scores that perfectly predict
which patients will benefit from any given treatment,
although several risk factors and proposed systems
exist.[55,56] Proposed classification systems include an
endoscopy-based score,[57,58] image-based approaches
including ultrasound [59,60] and computed tomography,[6163] as well as a combined clinicalradiological
physiology-based assessment.[64] A recent opinion-based,
consensus severity-grading system has been proposed for
emergency general surgery conditions including acute
diverticulitis, but currently lacks validation.[65] The variation
and approach to the disease assessments in the different
settings likely reflects the variable predominant populations
at risk seen by the different specialties; thus, endoscopists
and internists may be more prone to see patients with
less severe disease, and consequently rely on endoscopic
and ultrasonography findings, whereas surgeons typical see
patients with an acute abdomen and have potentially
more critically ill population to evaluate, and thus prefer
CT and vital signs-based scores.[55] Clearly, further studies
into the best classification system are needed.

Prevention of recurrence
Conservative treatment has become the primary choice in
the prevention of a recurrent episode of diverticulitis. A highfiber diet is still recommended in several guidelines despite
the fact that high-quality evidence for effectiveness of a
high-fiber diet in the treatment of diverticular disease is
lacking.
Lifestyle factors seem to have an impact on the course of
diverticular disease. Several prospective cohort studies and a
number of retrospective studies have found positive associations between obesity and diverticular complications.[48,49]
Smoking also increases the likelihood of complications in
diverticulitis.[66,67] Lifestyle counseling may need to be
given more emphasis in the (preventive) management of
diverticular disease and its complications. However, prospective evaluation of the effectiveness of lifestyle changes, once
diverticular disease has emerged, is required.
In the last few years, new medical therapies such as
probiotics (mainly Lactobacillus and Bifidobacteria) and
5-aminosalicylic acid (5-ASA; Mesalazine) have been studied.
Probiotics may seem a promising therapy for symptomatic
diverticular disease or for prevention of recurrent diverticulitis, but data are limited.[68]
Appraisal of a systematic review from 2010 shows only
two of the six included randomized clinical trials (RCTs) evaluating 5-ASA (Mesalazine) treatment enrolled patients with
diverticulitis and these studies were poor quality.[69] The
other four RCTs enrolled patients with diverticular disease. A
more recent systematic review demonstrated lack of good
evidence to support medical therapy with either 5-ASA or
probiotics, for the prevention of recurrent diverticulitis.[68]
Furthermore, after these reviews another four RCTs have
been performed, three negative trials and one positive
trial.[7073] Two North-American trials (PREVENT1 and
PREVENT 2) [70] have indicated no effect on reducing recurrence rates of recurrent attacks with mesalazine compared to
placebo. One study has found a statistically significant protective effect of mesalazine use with or without probiotics,
but the relapse rate in the placebo group was almost double
(46% vs. <30% for the other trials) and the subgroups are
hampered by small numbers.[73] Routine use of medical
therapy for relapse prevention after diverticulitis cannot be
recommended based on the available evidence.[74]

Implications for management

While the pathophysiology of acute diverticulitis needs further investigation, it is clear that it is not a strictly infectious disease for which every patient would need antibiotic
therapy to be cured. Current available data from Sweden
and the Netherlands randomized studies, the AVOD [25]
and DIABOLO trials,[75] suggest that conservative, nonantibiotic treatment can be applied in large number of
patients. Thus, understanding the role and differentiated
mechanisms between inflammation and infection needs to
be further elucidated, possibly with better biomarkers or
tools for stratification to select the best candidates for
either treatment choice.

SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY

Uncomplicated acute diverticulitis can to a larger extend

be managed as outpatients with no or little supportive therapy. This trend is increasingly recognized in currently
updated guidelines [76] and from prospective patient series
[28,29] but practice is still variable.[13,15,16] Risk assessment
remains a controversial area of debate, and the best risk
stratification tool is yet to be proved.[55,77,78]
For complicated acute diverticulitis, it is obviously important to identify those who are in need of surgery early, to
avoid the progression to severe disease, abdominal sepsis
and critical illness with organ failure. The presentation of
three recent randomized trials, the SCANDIV,[79] the DILALA
[80] and the LOLA trials,[81] that investigated the potential
for using laparoscopic lavage compared to the standard
Hartmanns approach (sigmoidectomy with end-stoma) for
acute purulent, perforated diverticulitis, have not proved a
superiority of lavage over resection. For true comparison of
short- and long-term complications and morbidity, longer
follow-up is needed to assess need for additional surgery,
numbers of stoma conversions and associated complications
that accumulates with further treatment in the follow-up
time.[2]

Conclusion
Acute colonic diverticulitis is a common disease, with a high
disease burden in modern society. Over- and under-treatment and over- and under-diagnosis of severity is likely due
to lack of reliable, robust and universal severity and classification systems. The incidence is likely to increase with the
growing and aging populations. While the disease mechanisms are still poorly understood, a clear distinction between
inflammation and infection has become more evident with
the successful non-antibiotic management in a considerable
number of cases. Further understanding of inflammatory factors and infectious components is needed. Risk markers of
disease progression or with ability to detect or predict
severe, complicated disease are needed for better disease
stratification. Long-term results from minimal-invasive and
comparative surgical trials may better help inform clinicians
and patients.

Disclosure statement

[5]

[6]

[7]
[8]

[9]

[10]

[11]

[12]
[13]

[14]

[15]

[16]

[17]

[18]

[19]

[20]

[21]

[22]

There are no conflicts of interest to disclose.

[23]

References
[1]

[2]

[3]
[4]

McDermott FD, Collins D, Heeney A, et al. Minimally invasive and

surgical management strategies tailored to the severity of acute
diverticulitis. Br J Surg. 2014;101:e90e99.
Boermeester MA, Humes DJ, Velmahos GC, et al. Contemporary
review of risk-stratified management in acute uncomplicated and
complicated diverticulitis. World J Surg. 2016; [Epub ahead of
print]. doi:10.1007/s00268-016-3560-8.
Humes D, Spiller RC. Colonic diverticular disease: medical treatments for acute diverticulitis. BMJ Clin Evid. 2016;2016: pii: 0405.
Jacobs DO. Clinical practice. Diverticulitis. N Engl J Med.
2007;357:20572066.

[24]

[25]

[26]
[27]

SSAT. SSAT patient care guidelines: surgical treatment of diverticulitis; 2007[cited 2014 Dec 31]. Available from: http://www.ssat.
com/cgi-bin/divert.cgi.
Andersen JC, Bundgaard L, Elbrond H, et al. Danish national
guidelines for treatment of diverticular disease. Dan Med J.
2012;59:C4453.
Fujita T. Feasibility of the practice guidelines for colonic diverticulitis. Surgery. 2012;151:491492.
Kruis W, Germer CT, Leifeld L. Diverticular disease: guidelines of
the German society for gastroenterology, digestive and metabolic
diseases and the German society for general and visceral surgery.
Digestion. 2014;90:190207.
Vennix S, Morton DG, Hahnloser D, et al. Systematic review of evidence and consensus on diverticulitis: an analysis of national and
international guidelines. Colorectal Dis. 2014;11:866878.
Eglinton TW, Frizelle FA. Trials of surgical treatment of acute perforated diverticulitis: finding what they look for. Ann Intern Med.
2016;164:195196.
Costi R, Zarzavadjian le Bian A, Smadja C, et al. Operative or nonoperative management of Hinchey III purulent acute diverticulitis?
Can J Surg. 2016;59:E2E3.
Centor RM. Acute uncomplicated diverticulitis: what to do until
we have better data. Ann Intern Med. 2016;164:120121.
Khan DZ, Kelly ME, OReilly J, et al. A national evaluation of the
management practices of acute diverticulitis. Surgeon. 2016;
doi:10.1016/j.surge.2015.12.004.
Wright GP, Flermoen SL, Robinett DM, et al. Surgeon specialization impacts the management but not outcomes of acute complicated diverticulitis. Am J Surg. 2015; 211:10351040.
OLeary DP, Lynch N, Clancy C, et al. International, expert-based,
consensus statement regarding the management of acute
diverticulitis. JAMA Surg. 2015;150:899904.
Jaung R, Robertson J, Rowbotham D, et al. Current management
of acute diverticulitis: a survey of Australasian surgeons. New
Zealand Med J. 2016;129:2329.
Granlund J, Svensson T, Olen O, et al. The genetic influence on
diverticular disease a twin study. Aliment Pharmacol Ther.
2012;35:11031107.
Strate LL, Erichsen R, Baron JA, et al. Heritability and familial
aggregation of diverticular disease: a population-based study
of twins and siblings. Gastroenterology. 2013;144:736742.e1.
quiz e14.
Comstock SS, Lewis MM, Pathak DR, et al. Cross-sectional analysis
of obesity and serum analytes in males identifies sRAGE as a
novel biomarker inversely associated with diverticulosis. PLoS
One. 2014;9:e95232.
Daniels L, Philipszoon LE, Boermeester MA. A hypothesis: important role for gut microbiota in the etiopathogenesis of diverticular
disease. Dis Colon Rectum. 2014;57:539543.
Lahner E, Bellisario C, Hassan C, et al. Probiotics in the treatment
of diverticular disease. A systematic review. J Gastrointestin Liver
Dis. 2016;25:7986.
Daniels L, Budding AE, de Korte N, et al. Fecal microbiome analysis as a diagnostic test for diverticulitis. Eur J Clin Microbiol
Infect Dis. 2014;33:19271936.
Spiller RC. Changing views on diverticular disease: impact of
aging, obesity, diet, and microbiota. Neurogastroenterol Motil.
2015;27:305312.
Ferguson LR, Laing B, Marlow G, et al. The role of vitamin D in
reducing gastrointestinal disease risk and assessment of individual
dietary intake needs: focus on genetic and genomic technologies.
Mol Nutr Food Res. 2016;60:119133.
Chabok A, Pahlman L, Hjern F, et al. Randomized clinical trial of
antibiotics in acute uncomplicated diverticulitis. Br J Surg.
2012;99:532539.
de Korte N, Unlu C, Boermeester MA, et al. Use of antibiotics in
uncomplicated diverticulitis. Br J Surg. 2011;98:761767.
Moya P, Arroyo A, Perez-Legaz J, et al. Applicability, safety and
efficiency of outpatient treatment in uncomplicated diverticulitis. Tech Coloproctol. 2012;16:301307.

K. SREIDE ET AL.

[28]

Mali JP, Mentula PJ, Leppaniemi AK, et al. Symptomatic treatment

for uncomplicated acute diverticulitis: a prospective cohort
study. Dis Colon Rectum. 2016;59:529534.
Brochmann N, Schultz JK, Jakobsen GS, et al. Management of
acute uncomplicated diverticulitis without antibiotics: a single
center cohort study. Colorectal Dis. 2016; [Epub ahead of print].
doi:10.1111/codi.13355.
Parks TG. Natural history of diverticular disease of the colon. Clin
Gastroenterol. 1975;4:5369.
Eide TJ, Stalsberg H. Diverticular disease of the large intestine in
Northern Norway. Gut. 1979;20:609615.
Lee YS. Diverticular disease of the large bowel in Singapore. An
autopsy survey. Dis Colon Rectum. 1986;29:330335.
Munakata A, Nakaji S, Takami H, et al. Epidemiological evaluation
of colonic diverticulosis and dietary fiber in Japan. Tohoku J Exp
Med. 1993;171:145151.
Nakaji S, Danjo K, Munakata A, et al. Comparison of etiology of
right-sided diverticula in Japan with that of left-sided diverticula
in the West. Int J Colorectal Dis. 2002;17:365373.
Nguyen GC, Sam J, Anand N. Epidemiological trends and geographic variation in hospital admissions for diverticulitis in the
United States. World J Gastroenterol. 2011;17:16001605.
Masoomi H, Buchberg BS, Magno C, et al. Trends in diverticulitis
management in the United States from 2002 to 2007. Arch Surg.
2011;146:400406.
Etzioni DA, Chiu VY, Cannom RR, et al. Outpatient treatment of
acute diverticulitis: rates and predictors of failure. Dis Colon
Rectum. 2010;53:861865. 10.1007/DCR.0b013e3181cdb243.
Etzioni DA, Mack TM, Beart RWJ, et al. Diverticulitis in the United
States: 1998-2005: changing patterns of disease and treatment.
Ann Surg. 2009;249:210217.
Kang JY, Hoare J, Tinto A, et al. Diverticular disease of the colon
on the rise: a study of hospital admissions in England between
1989/1990 and 1999/2000. Aliment Pharmacol Therapeut.
2003;17:11891195.
Jeyarajah S, Faiz O, Bottle A, et al. Diverticular disease hospital
admissions are increasing, with poor outcomes in the elderly
and emergency admissions. Aliment Pharmacol Therapeut.
2009;30:11711182.
Crowe FL, Appleby PN, Allen NE, et al. Diet and risk of diverticular
disease in the European Prospective Investigation into Cancer
and Nutrition (EPIC)-Oxford cohort: a prospective study of British
Vegetarians and non-vegetarians. BMJ. 2011. doi: 10.1136/
bmj.d4131.
Crowe FL, Balkwill A, Cairns BJ, et al. Source of dietary fibre and
diverticular disease incidence: a prospective study of UK women.
Gut. 2014;63:14501456.
Aldoori WH, Giovannucci EL, Rimm EB, et al. Prospective study of
physical activity and the risk of symptomatic diverticular disease
in men. Gut. 1995;36:276282.
Strate LL, Liu YL, Syngal S, et al. Nut, corn, and popcorn consumption and the incidence of diverticular disease. JAMA
2008;300:907914.
Tonnesen H, Engholm G, Moller H. Association between alcoholism and diverticulitis. Br J Surg. 1999;86:10671068.
Aldoori WH, Giovannucci EL, Rimm EB, et al. A prospective study
of alcohol, smoking, caffeine, and the risk of symptomatic diverticular disease in men. Ann Epidemiol. 1995;5:221228.
Hjern F, Wolk A, Hakansson N. Smoking and the risk of diverticular disease in women. Br J Surg. 2011;98:9971002.
Strate LL, Liu YL, Aldoori WH, et al. Obesity increases the risks of
diverticulitis and diverticular bleeding. Gastroenterology.
2009;136:115122.e1. doi:10.1053/j.gastro.2008.09.025.
Hjern F, Wolk A, Hakansson N. Obesity, physical inactivity, and
colonic diverticular disease requiring hospitalization in women: a
prospective cohort study. Am J Gastroenterol. 2012;107:296302.
Strate LL, Liu YL, Aldoori WH, et al. Physical activity decreases
diverticular complications. Am J Gastroenterol. 2009;104:
12211230.

[29]

[30]
[31]
[32]
[33]

[34]

[35]

[36]

[37]

[38]

[39]

[40]

[41]

[42]

[43]

[44]

[45]
[46]

[47]
[48]

[49]

[50]

[51]

[52]

[53]
[54]

[55]
[56]
[57]

[58]

[59]
[60]

[61]

[62]

[63]

[64]

[65]

[66]

[67]

[68]

[69]

[70]

[71]

[72]

Skoldberg F, Svensson T, Olen O, et al. A population-based casecontrol study on statin exposure and risk of acute diverticular disease. Scand J Gastroenterol. 2016;51:203210.
Virgilio E, Balducci GE. John Hinchey (1934 to present): father of
modern age of acute complicated diverticulitis of the colon.
World J Surg. 2016; [Epub ahead of print]. doi:10.1007/s00268016-3546-6.
Hinchey EJ, Schaal PG, Richards GK. Treatment of perforated
diverticular disease of the colon. Adv Surg. 1978;12:85109.
Wasvary H, Turfah F, Kadro O, et al. Same hospitalization
resection for acute diverticulitis. Am Surg. 1999;65:632635. discussion 6.
Tan JP, Barazanchi AW, Singh PP, et al. Predictors of acute diverticulitis severity: a systematic review. Int J Surg. 2016;26:4352.
Pfutzer RH, Kruis W. Management of diverticular disease. Nat Rev
Gastroenterol Hepatol. 2015;12:629638.
Tursi A, Brandimarte G, Di Mario F, et al. Predictive value of the
Diverticular Inflammation and Complication Assessment (DICA)
endoscopic classification on the outcome of diverticular disease
of the colon: an international study. UEG J. 2016;4:604613.
Tursi A, Brandimarte G, Di Mario F, et al. Development and validation of an endoscopic classification of diverticular disease of the
colon: the DICA classification. Dig Dis. 2015;33:6876.
Lembcke B. Ultrasonography in acute diverticulitis credit where
credit is due. Z Gastroenterol. 2016;54:4757.
Lembcke BJ, Strobel D, Dirks K, et al. Statement of the section
internal medicine of the DEGUM ultrasound obtains pole position for clinical imaging in acute diverticulitis. Ultraschall Med.
2015;36:191195.
Thorisson A, Smedh K, Torkzad MR, et al. CT imaging for prediction of complications and recurrence in acute uncomplicated
diverticulitis. Int J Colorectal Dis. 2015;31:451457.
Sartelli M, Moore FA, Ansaloni L, et al. A proposal for a CT driven
classification of left colon acute diverticulitis. World J Emerg Surg.
2015;10:3.
Flor N, Maconi G, Sardanelli F, et al. Prognostic value of the diverticular disease severity score based on CT colonography: followup in patients recovering from acute diverticulitis. Acad Radiol.
2015;22:15031509.
Sallinen VJ, Leppaniemi AK, Mentula PJ. Staging of acute diverticulitis based on clinical, radiologic, and physiologic parameters.
J Trauma Acute Care Surg. 2015;78:543551.
Tominaga GT, Staudenmayer KL, Shafi S, et al. The American
Association for the Surgery of Trauma Grading Scale for 16 emergency general surgery conditions: disease-specific criteria characterizing anatomic severity grading. J Trauma Acute Care Surg.
2016; [Epub ahead of print]. doi:10.1097/ta.0000000000001127.
Papagrigoriadis S, Macey L, Bourantas N, et al. Smoking may be
associated with complications in diverticular disease. Br J Surg.
1999;86:923926.
Turunen P, Wikstrom H, Carpelan-Holmstrom M, et al. Smoking
increases the incidence of complicated diverticular disease of the
sigmoid colon. Scand J Surg. 2010;99:1417.
Unlu C, Daniels L, Vrouenraets BC, et al. Systematic review of
medical therapy to prevent recurrent diverticulitis. Int J Colorectal
Dis. 2012;27:11311136.
Gatta L, Vakil N, Vaira D, et al. Efficacy of 5-ASA in the treatment
of colonic diverticular disease. J Clin Gastroenterol.
2010;44:113119.
Raskin JB, Kamm MA, Jamal MM, et al. Mesalamine did not prevent recurrent diverticulitis in phase 3 controlled trials.
Gastroenterology. 2014;147:793802.
Stollman N, Magowan S, Shanahan F, et al. A randomized controlled study of mesalamine after acute diverticulitis: results of
the DIVA trial. J Clin Gastroenterol. 2013;47:621629.
Parente F, Bargiggia S, Prada A, et al. Intermittent treatment with
mesalazine in the prevention of diverticulitis recurrence: a randomized multicentre pilot double-blind placebo-controlled study of
24-month duration. Int J Colorectal Dis. 2013;28:14231431.

SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY

[73]

[74]

[75]

[76]

Tursi A, Brandimarte G, Elisei W, et al. Randomised clinical trial:

mesalazine and/or probiotics in maintaining remission of symptomatic uncomplicated diverticular disease a double-blind,
randomised, placebo-controlled study. Aliment Pharmacol Ther.
2013;38:741751.
Sallinen VJ, Mentula PJ, Leppaniemi AK. Nonoperative
management of perforated diverticulitis with extraluminal air is
safe and effective in selected patients. Dis Colon Rectum.
2014;57:875881.
Unlu C, de Korte N, Daniels L, et al. A multicenter randomized
clinical trial investigating the cost-effectiveness of treatment
strategies with or without antibiotics for uncomplicated acute
diverticulitis (DIABOLO trial). BMC Surg. 2010;10:23.
Strate LL, Peery AF, Neumann I. American Gastroenterological
Association Institute technical review on the management of
acute diverticulitis. Gastroenterology. 2015;149:19501976.e12.

[77]

[78]

[79]

[80]

[81]

Makela JT, Klintrup K, Rautio T. The role of low CRP values in the
prediction of the development of acute diverticulitis. Int J
Colorectal Dis. 2016;31:2327.
Hogan J, Sehgal R, Murphy D, et al. Do inflammatory indices play
a role in distinguishing between uncomplicated and complicated
diverticulitis? Digest Surg. 2016;34:711.
Schultz JK, Yaqub S, Wallon C, et al. Laparoscopic lavage vs primary resection for acute perforated diverticulitis: the SCANDIV
randomized clinical trial. JAMA. 2015;314:13641375.
Thornell A, Angenete E, Bisgaard T, et al. Laparoscopic lavage
for perforated diverticulitis with purulent peritonitis: a randomized trial. Ann Intern Med. 2016;164:137145.
Vennix S, Musters GD, Mulder IM, et al. Laparoscopic peritoneal
lavage or sigmoidectomy for perforated diverticulitis with
purulent peritonitis: a multicentre, parallel-group, randomised,
open-label trial. Lancet. 2015;386:12691277.