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. 2021 Jan 25;57(2):108. doi: 10.3390/medicina57020108

Association of Colonic Diverticula with Colorectal Adenomas and Cancer

Angelo Viscido 1,†, Fabiana Ciccone 2,†, Filippo Vernia 1, Dolores Gabrieli 2, Annalisa Capannolo 1, Gianpiero Stefanelli 1, Stefano Necozione 3, Giorgio Valerii 2, Hassan Ashktorab 4, Giovanni Latella 1,*
Editor: Roberto Cirocchi
PMCID: PMC7910864  PMID: 33504050

Abstract

Background and Objectives: Conflicting evidence is reported regarding any association between colonic diverticula with colorectal adenomas or cancer. The present study aimed to evaluate, in a cohort of Caucasian patients, the association between colonic diverticula and colorectal polyps and cancer. Materials and Methods: All consecutive patients undergoing colonoscopy at our institution were included in the study. The presence and location of diverticula, polyps, and cancers were recorded. Histologically, polyps were classified as adenoma (with low or high dysplasia), hyperplastic, or inflammatory. The relative risk of the association of polyps and cancer with diverticula was assessed. Multiple logistic regression analyses, including age, sex, family history for colorectal cancer (CRC), and family history for diverticula, were carried out. Results: During the study period, 1490 patients were enrolled; 37.2% (n = 555) showed colonic diverticula or polyps or CRC (308 males, mean age 66 years). Particularly, 12.3% (n = 183) patients presented only diverticula, 13.7% (n = 204) only polyps or cancer, 11.3% (n = 168) both diseases, and 62.7% (n = 935) neither diverticula nor polyps and cancer. A total of 38 patients presented colorectal cancer, 17 of which had also diverticula. A significant increase in relative risk (RR 2.81, 95% CI 2.27–3.47, p < 0.0001) of colorectal adenoma and cancer in patients with colonic diverticula was found. At multivariate analysis, only diverticula resulted to be significantly associated with colorectal adenomas and cancer (Odds Ratio, OR 3.86, 95% CI 2.90–5.14, p < 0.0001). Conclusions: A significant association of colonic diverticula with colorectal adenoma or cancer was found. This implies that patients with colonic diverticula require a vigilant follow-up procedure for the prevention of colorectal cancer from those applicable to the general population.

Keywords: diverticulosis, diverticulitis, diverticular disease, colorectal polyps, colorectal adenoma, colorectal cancer

1. Introduction

Colonic diverticula and colorectal polyps and cancer are common findings during colonoscopy, especially in patients over 50 years of age [1]. Most patients with diverticula of the colon remain asymptomatic throughout their lives, a condition commonly referred to as diverticulosis or asymptomatic diverticula. Approximately 20% of those with colonic diverticula develop symptoms (abdominal pain or discomfort, bloating, constipation, or diarrhea), conditions described under the general heading of symptomatic diverticular disease (DD), which may be uncomplicated, recurrent, or complicated [2,3,4]. Symptomatic DD includes the types without inflammation (symptomatic uncomplicated diverticular disease (SUDD)) and those with overt inflammation of the colon, including both segmental colitis associated with diverticula (SCAD) and diverticulitis [5]. This latter form can be acute or chronic, uncomplicated, or complicated.

Patients with colorectal polyps and early colorectal cancer (CRC) are, in most cases, asymptomatic [6,7]. Bowel habit alterations and/or hematochezia appear in a minority of cases and only in the presence of large and multiple polyps or ulcerated and/or stenotic CRC. The screening tests are aimed at detecting asymptomatic polyps and CRC [8,9]. A recent study demonstrated that bleeding-related signs (overt bleeding, iron deficiency anemia, or a positive fecal occult blood test) are present in three-quarters of patients with CRC. Both overt and occult bleeders are less likely than non-bleeders to have metastases at diagnosis. Overt bleeders are very unlikely to present with obstructive symptoms and most occult bleeders are found to have proximal cancer [10].

The prevalence of both diverticula and colorectal neoplasia increases exponentially with age.

Under the age of 40, the frequency of diverticula is estimated at approximately 5%, increasing to 65–70% for those over 65 [11].

CRC is a highly common malignancy in European countries and the world in general [12,13,14].

According to GLOBOCAN data, 1.36 million new cases, affecting 17.2 per 100,000 populations, are diagnosed worldwide each year and 693,000 people die from CRC, amounting to a yearly mortality rate of 8.4 per 100,000 [14]. CRC has become a major public health concern because, despite treatment, as many as half of CRC patients die from the disease [13]. CRC is sporadic in 90% of patients, whereas in <10% it is inherited [15,16] or can be the complication result of inflammatory bowel disease (IBD), either ulcerative colitis (UC) or Crohn’s disease (CD) [17,18,19,20]. In most cases, CRC develops from adenoma, a preclinical benign precursor, the progression from early adenoma to invasive cancer taking years [21]. The estimated CRC lifetime risk is 5–6% with incidence rates increasing sharply after the age of 50 [21,22].

In addition to age, diverticula and colorectal neoplasms appear to share other risk factors, such as a diet low in fibers and rich in saturated fats, obesity, and slow colonic transit time [1,2].

Inflammation also seems to be a common finding shared by the two conditions, the presence of a chronic inflammatory process increasing the risk of a malignant transformation [20,23,24]; chronic microscopic inflammation of the colon has been reported in DD, even in the SUDD [25].

All this evidence gives rise to the hypothesis of a possible association between diverticula and colorectal adenomas and cancer. However, contrasting results have been reported as some studies supporting this thesis [1,26,27,28,29], while others demonstrate an absence of this association [30,31,32]. Most of the evidence available in literature derives from retrospective studies, and the results from the few prospective cohorts are discordant, especially among different ethnic groups. Thus, further prospective studies are needed to establish the real relationship between DD, colorectal polyps, and CRC, as this could have important implications for CRC screening programs. The present study aimed to evaluate, in a cohort of Caucasian patients, the association between colonic diverticula, colorectal polyps, and cancer.

2. Materials and Methods

2.1. Study Population

This prospective study was carried out at the Gastroenterology Unit of the Medical School of the University of L’Aquila, L’Aquila, Italy, and the Gastroenterology Unit, Giuseppe Mazzini Hospital, Teramo, Italy.

All consecutive patients who underwent colonoscopy in the period between September 2016 and September 2019 were included. Patients underwent the procedure for a variety of reasons: uncomplicated lower abdominal pain or discomfort, hematochezia, changes in bowel habit, weight loss, iron-deficiency anemia, chronic constipation, chronic diarrhea, surveillance after colonic polypectomy, and screening for CRC.

Ethics Committee Approval: The study was performed with the institutional review board’s approval (Prot. N. 43958). All clinical investigations were conducted according to the principles laid down in the Declaration of Helsinki.

Informed consent: Written informed consent was obtained from all patients included in the present study.

2.2. Colonoscopy and Histopathology

Before the colonoscopy, patients received a polyethylene glycol solution for bowel preparation and intravenous diazepam or midazolam for sedation. During the study period, 1994 colonoscopies were performed. A total of 504 patients did not meet the inclusion criteria, as 311 were affected by IBD, infectious colitis, or ischemic colitis, 137 had poor bowel cleansing (Boston score 0–1) [33], 54 had incomplete endoscopic examination, and 2 had polyps close to the scar, resulting from previous polypectomies. A total of 1490 patients were therefore enrolled and included in the statistical analysis. All enrolled patients were divided into four groups according to the endoscopic findings: group A, patients with only DD; group B, patients with only polyps or CRC; group C, patients showing both DD and polyps or CRC; and group D, patients without diverticula, polyps, or cancer (Figure 1). Data were recorded on a standard database.

Figure 1.

Figure 1

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Study population.

Colonoscopy findings were documented using a standardized colonoscopy-reporting system. Colonic diverticula are characterized by the herniation of the colonic mucosa and submucosa through defects in the muscle layer at the weakest point in the colonic wall. Diverticulosis was defined as the presence of at least two diverticula, in the absence of symptoms. DD was defined as intestinal symptoms and signs related to the presence of colonic diverticula [5,34].

Colorectal polyps were classified according to their location and histopathology. We defined the proximal colon as the cecum, ascending colon, and transverse colon, including splenic flexure, distal colon as descending colon, sigmoid colon, and rectum. All polyps were removed with a forceps biopsy (polyps < 5 mm) or a diathermic loop (polyps > 5 mm), as appropriate. Multiple biopsies were taken from CRC.

Histological samples were classified as cancer, adenoma (with low or high dysplasia), hyperplastic, or inflammatory polyps.

2.3. Statistical Analysis

Comparisons among the groups were assessed by the chi-square test and Fisher’s exact test, as appropriate, for categorical variables. The relative risk (RR), with the 95% confidence intervals of the association of polyps and cancer with diverticula, was assessed. Multiple logistic regression analyses, including age, sex, family history for CRC, and family history for diverticula, were carried out. All statistical analyses were performed using the STATA version 15.1 2017 (StataCorp LLC, College Station, TX, USA).

3. Results

Of the 1490 patients enrolled, 37.2% (555/1490) showed colonic diverticula, polyps, or CRC (308 M, 247 F, mean age 66 years). In particular, 23.5% (351/1490) showed colonic diverticula, 15.0% (224/1490) colorectal adenomas, 2.5% (37/1490) CRC, 6.5% (97/1490) hyperplastic polyps, 0.9% (14/1490) inflammatory polyps, and 62.7% (935/1490) had other different lesions, such as proctitis, angiodysplasia, hemorrhoids, or no mucosal lesions. The study population was divided into four patient groups (Figure 1): Group A: 12.3% patients (183) with only diverticula (52% male vs. 48% female); Group B: 13.7% patients (204) with only polyps or cancers (53% male vs. 47% female); Group C: 11.3% patients (168) with both diverticula and polyps or cancers (62% male vs. 38% female); Group D: 62.7% patients (935) without neoplastic lesions or diverticula (56% male vs. 44% female).

Clinical characteristics of the four groups of patients are summarized in Table 1. Histological characteristics and localization of neoplastic lesions and diverticula of Group C (patients with both polyps or CRC and diverticula) are summarized in Table 2. In this group of patients, most polyps were found in the distal colon.

Table 1.

Demographic and clinical characteristics.

GROUP A GROUP B GROUP C GROUP D
Diverticula Polyps or Cancer Polyps or Cancer and Diverticula No Diverticula, Polyps, or Cancer
(N.183) (N.204) (N.168) (N.935)
Age (Years)
Median (Range) 68 (27–92) 63 (21–93) 68 (47–92) 65 (29–90)
Sex
Female N (%) 88 (48%) 95 (47%) 64 (38%) 410 (44%)
Male N (%) 95 (52%) 109 (53%) 104 (62%) 525 (56%)
Family history of CRC
Negative N (%) 166 (90.71%) 152 (74.51%) 143 (85.12%) 783 (83.74%)
Positive N (%) 17 (9.29%) 52 (25.49%) 25 (14.88%) 152 (16.26%)
Family history of DD
Negative N (%) 178 (97.27%) 202 (99.02) 160 (95.24%) 910 (97.33%)
Positive N (%) 5 (2.73%) 2 (0.98) 8 (4.76%) 25 (2.67%)
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Colorectal cancer (CRC); diverticular disease (DD).

Table 2.

Histological characteristics and localization of colorectal polyps and cancer in patients with diverticula of the colon (Group C).

Localization of Diverticula in the Colon Tracts Histology
Inflammatory
Polyps
N (%)
10 (6.0%)		 Hyperplastic Polyps
N (%)
37 (22.0%)		 Adenomas
N (%)
104 (61.9%)		 Cancer
N (%)
17 (10.1%)
Proximal colon 0 2 (5.4%) 2 (1.9%) 2 (11.8%)
Distal colon 10 (100%) 29 (78.4%) 70 (67.3%) 15 (88.2%)
Proximal and distal colon 0 6 (16.2%) 32 (30.8%) 0
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In particular, inflammatory polyps were only found in the distal colon. The histological distribution of all polyps and cancers found in Group B (patients with only polyps or cancer), in Group C (patients with both diverticula and polyps or cancers), and Group B + Group C is shown in Figure 2; the most frequent histological finding was adenomatous polyps, accounting for 60% (n = 224) of all lesions.

Figure 2.

Figure 2

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Histological distribution of all polyps and cancers found in Group B (patients with only polyps or cancer), in Group C (patients with both diverticula and polyps or cancers), and Group B + Group C.

Out of all the 555 patients (Group A + Group B + Group C), 6.7% (37) of them showed a CRC; out of these, 45.9% (17) also showed diverticula. Adenomatous polyps were found in 40.4% (224/555) patients; out of these, 104 (45.4%) also showed diverticula. Hyperplastic polyps were found in 17.5% (97/555) patients; out of these, 38.1% (37) also showed diverticula. Inflammatory polyps were found in 2.5% (14/555) patients; out of these, 71.4% (10) also showed diverticula.

The RR of the association of polyps and cancer with diverticula was assessed. A significant increase in RR of the association of polyps and cancer with diverticula of the colon was found. The RR was higher when only adenomas and cancer were evaluated compared to all types of polyps and cancer (2.81 vs. 2.67, respectively) (Table 3 and Table 4).

Table 3.

The relative risk of the association of colorectal polyps and cancer with diverticula of the colon.

Polyps and Cancers Diverticula Total
Absent Present
Absent 935 183 1118 (75.0%)
Present 204 168 372 (25.0%)
Total 1139 351 1490
Relative risk
2.67
95% CI
2.27 to 3.15
Significance level
p < 0.0001
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Table 4.

Relative risk of the association of colorectal adenoma and cancer with diverticula of the colon.

Adenoma and Cancers Diverticula Total
Absent Present
Absent 999 230 1229 (82.5%)
Present 140 121 261 (17.5%)
Total 1139 351 1490
Relative risk
2.81
95% CI
2.27 to 3.47
Significance level
p < 0.0001
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At multivariate analysis (Table 5), of the demographic (age, sex) and clinical parameters (family history of colonic diverticula and neoplastic lesions) considered, only diverticula resulted to be significantly associated with colorectal adenomas and cancer (odds ratio (OR) 3.86, 95% CI 2.90–5.14, p < 0.0001).

Table 5.

Multivariate analysis with logistic regression and adjusted odds ratios (OR). Multiple logistic regression analyses including age, sex, family history for CRC, family history for diverticula, and presence of diverticula were carried out to investigate the independent association with colorectal polyps.

Variables Odds Ratio p Value
(95% CI)
Age
per year 1.00 (0.99–1.01) 0.753
Sex
female 1 (reference) 0.836
male 0.97 (0.74–1.28)
Family history of CRC
No 1 (reference) 0.162
Yes 1.32 (0.90–1.94)
Family history of DD
No 1 (reference) 0.467
Yes 0.71 (0.28–1.78)
Diverticula
No 1 (reference) <0.0001
Yes 3.86 (2.90–5.14)
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4. Discussion

Colon cancer could be associated with a history of diverticular disease and personal history of polyps that may be detected during colonoscopy, especially in older patients (>50 years old).

Many studies have been conducted on colonic diverticula but they are heterogeneous due to the different study designs (prospective, retrospective, case-control), the different classes of patients considered (population-based, hospital-admitted, outpatients, etc.), the various methods employed for the diagnosis of diverticula (barium enema, computed tomography (CT), surgery, endoscopy), and the different diseases for which the evaluations were conducted (diverticular disease, diverticulitis, polyps, adenoma, cancer) (Table 6) [1,26,27,28,29,30,31,32,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70].

Table 6.

Studies evaluating the association between colonic diverticula and colorectal neoplasia.

Study Study Design N. Patients Mean Age Outcomes Assessed Diagnosis Association
McCallum A
1988 [35]		 Retrospective 119 -- Association between diverticulosis and CRC Barium enema no
Morini S
1988 [36]		 Case-control study 150 57.0 Association between diverticular disease, adenomas, and CRC Colonoscopy Yes for adenomas
No for CRC
Stefansson T
1993 [37]		 Retrospective 7159 -- Association between diverticulosis or diverticulitis and CRC Nationwide register Two-fold
increase in the RR of left-sided CRC in patients with diverticulosis or diverticulitis.
Yusuf MA
2000 [38] a 		Retrospective 311 45.3 Association between diverticular disease and CRC Colonoscopy no
Loffeld R.J
2002 [39]		 Retrospective 9086 52.0 without DD
69.0 with DD		 Association between diverticulosis and CRC or polyps
(histological type unspecified)		 Colonoscopy No for CRC
yes for polyps
Morini S
2002 [26]		 Prospective 630 66.8 with DD
61.5 without DD		 Association between diverticular disease, adenomas, and CRC Colonoscopy Yes for adenomas
No for CRC
Stefansson T
2004 [40]		 Retrospective 7159 -- Association between sigmoid diverticulitis and increased risk of left-side CRC Barium enema yes
Kieff BJ
2004 [41]		 Prospective 502 58.6 Association between diverticulosis and CRC Colonoscopy CT scan surgery barium enema Yes, only for women with extensive distal diverticulosis
Rajendra S
2005 [42]		 Prospective 410 51.7 Association between diverticular disease and adenomas Colonoscopy yes
Soran A
2006 [43]		 Retrospective 1561 67.0 with DD
and CRC
61.0 only with DD		 Association between diverticulosis and CRC Surgery no
Krones CJ
2006 [44]		 Retrospective 1326 64.0 Association between diverticulosis or diverticulitis and CRC Surgery no
Choi CS
2007 [45]		 Retrospective 2377 50.8 Association between diverticulosis and CRC Colonoscopy yes
Rangnekar AS
2007 [46] a 		Prospective 308 -- Association of diverticulosis and polyps Colonoscopy yes
Hirata T
2008 [47]		 Retrospective 672 58.0 Association between diverticular disease and colonic polyps Colonoscopy yes
Meurs-Szojda MM 2008 [30] Retrospective 4241 59.0 Association of diverticulosis, diverticulitis, polyps, and CRC Colonoscopy no
Hammoud I
2009 [48] a 		Retrospective 1668 -- Association of diverticulosis and polyps Colonoscopy no
Lee KM
2010 [49]		 Prospective 1030 52.2 Association of diverticulosis and polyps Colonoscopy yes
Mazumder MK
2011 [50] a 		Retrospective 1000 57.3 Association of diverticulosis and polyps Colonoscopy yes
Neubauer K
2011 [51] a 		Retrospective 1776 52.5 Association between diverticulosis and colorectal adenomas and CRC Colonoscopy Yes for adenomas
No for CRC
Rondagh EJ
2011 [1]		 Prospective 2310 58.4 Association between diverticulosis and colorectal polyps (adenoma, serrated polyp, advanced CRC) Colonoscopy yes
Grandlund J
2011 [31]		 Retrospective 41,037 75.0 F
73.0 M		 Association between diverticular disease and CRC CT-scan Colonoscopy no
Szura M
2011 [52] a 		Retrospective 22,441 55.1 Association of diverticulosis and polyps Colonoscopy yes
Gohil VB
2012 [28]		 Retrospective 300 57.0 Association between diverticulosis and adenoma detection rate Colonoscopy yes
Lee SJ
2012 [53]		 Prospective 604 56.9 Association of diverticulosis and CRC CT-colonography no
Azzam N
2013 [54]		 Retrospective 270 60.82 Association among colonic polyps, comorbidities, and diverticular disease Colonoscopy Yes for diverticulosis and adenomas
Parava P
2013 [55] a 		Retrospective 1077 57.0 Association of diverticulosis and polyps Colonoscopy yes
Muhammad A
2014 [29]		 Retrospective 2223 63.0 with DD
59.0 without DD		 Association between diverticulosis and colorectal polyps (adenomas and advanced adenomas) Colonoscopy Yes for adenomas
Lecleire S
2014 [56]		 Retrospective 404 60.9 with DD
60.7 without DD		 Association between acute diverticulitis and colorectal polyps Colonoscopy no
Meda S
2014 [57] a 		Retrospective 890 -- Association of diverticulosis and polyps Colonoscopy no
Shen H
2014 [58] a 		Prospective 1363 59.3 Association of diverticulosis and adenomas Colonoscopy no
Huang WY
2014 [59]		 Retrospective 41,359 56.0 Association between diverticulosis or diverticulitis and CRC Colonoscopy no
Ashktorab H
2015 [27]		 Retrospective 1986 57.0 Association between diverticulosis and pre-neoplastic colonic lesions (hyperplastic polyps and adenomas) Colonoscopy yes
Peery AF
2015 [32]		 Prospective 624 56.0 with adenoma
53.0 without		 Association between colonic diverticula and adenomas or advanced adenomas Colonoscopy no
Wang FW
2015 [60]		 Prospective 1899 52.8 Association of diverticulosis and adenomas Colonoscopy yes
Wong ER
2016 [61]		 Retrospective 2766 53.2 Association between colonic diverticula and CRC or polyps (not specified the histological type) Colonoscopy yes
Levine I
2017 [62]		 Retrospective 589 63 with D
58 without D		 Association between colonic diverticula and CRC or polyps Colonoscopy no
Shah R
2017 [63] a 		Retrospective 896 -- Association of diverticulosis and polyps Colonoscopy yes
Teixeira C
2017 [64]		 Prospective 203 65.5 Association of diverticulosis and adenomas Colonoscopy no
Hong W
2018 [65]		 Prospective 17,456 53.5 with D
49 without D		 Association of diverticulosis or location of diverticulosis and adenoma or advanced adenoma Colonoscopy no
Pavão Borges V 2018 [66] a Retrospective 414 67.2 Association of diverticulosis and adenomas Colonoscopy no
Rodriguez-Castro K 2018 [67] a Prospective 25,962 67.2 with D
58.1 without D		 Association between colonic diverticula and CRC or polyps Colonoscopy Yes for adenomas
No for CRC
Schramm C
2018 [68]		 Retrospective 4196 65.6 with D
62.0 without D		 Association between colonic diverticula and CRC or polyps Colonoscopy Yes for adenomas
No for CRC
Wang SF
2019 [69]		 Retrospective 346,118 56 Association between colonic diverticula and CRC or polyps Colonoscopy yes
Tomaoglu K
2020 [70]		 Retrospective 3496 51.3 M
53.3 F		 Association between diverticulosis and CRC or polyps Colonoscopy Yes for adenomas
No for CRC
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CRC = Colorectal Cancer; DD = Diverticular Disease; RR = Relative Risk; CT = Computed Tomography; a = Data published only in Abstracts.

Most of the evidence available in literature derives from retrospective studies. However, large prospective cohorts have been recently described in Asia [42,49,53,60,65]. Excluding data published in the form of an abstract, to our knowledge, only three prospective studies have been carried out in Caucasian patients [1,26,64] and two in mixed cohorts from the USA [32,41] (Table 6). The incidence and distribution of diverticula in the colon is different between Western countries and Asian countries. In the former, the diverticula are more frequent and develop more in the left colon, while in the latter they predominate in the right colon [2,3,4,5].

In this prospective study, including all consecutive Caucasian patients, we found a significant association of colonic diverticula with colorectal adenomas or cancer. Additionally, the majority of all polyps (including both inflammatory and adenomatous polyps) were found in the distal colon, where diverticula were also more frequently present.

A recent meta-analysis involving 29 cross-sectional studies reported that diverticula were associated with increased risk of adenomas (OR 1.47, 95% CI 1.18–1.84) and with the more lax-defined “polyps” (OR 1.95, 95% CI 1.15–3.31), but not with CRC (OR 0.98, 95% CI 0.63–1.50) [71], as reported in an old case-control study [36]. Interestingly, a sub-analysis showed that diverticulosis did not increase the risk of adenomas (OR 1.34, 95% CI 0.87–2.06) in patients who underwent screening colonoscopy [71]. The latter result might be related by the younger age of patients undergoing their first endoscopic CRC-screening. However, this work shows some limitations, such as the inclusion of cross-sectional studies (in which the causal relationship is difficult to assess), studies in which polyps were defined morphologically regardless of histologic evaluation, and the inclusions of data reported only in the form of abstracts.

In contrast with the results of the aforementioned meta-analysis [71], a cross-sectional study involving 2310 patients by Rondagh et al. reported that the association of diverticulosis with colorectal polyps was influenced by patient age: only below the age of 60 was the prevalence of colorectal polyps significantly higher in patients with diverticulosis than in those without diverticulosis [1]. An association with the female gender has also been described [41].

In the present study, all subtypes of polyps have been considered. The majority of all polyps were found in the distal colon. In particular, inflammatory polyps were only found in the distal colon. Adenomas accounted for 60% of all polyps. A significant increase in relative risk (RR 2.81, 95% CI 2.27–3.47, p < 0.0001) of colorectal adenoma and cancer in patients with colonic diverticula was found. At multivariate analysis, of the demographic and clinical parameters considered, only diverticula resulted in a significant association with colorectal adenomas and cancer (OR 3.86, 95% CI 2.90–5.14, p < 0.0001).

The location of inflammatory polyps in the distal colon confirms literature data, probably due to the presence of a mucosal inflammation of this colonic tract more commonly involved by diverticula [25,72,73,74,75]. Inflammatory polyps develop as a result of an exuberant mucosal regeneration and repair of mucosal inflammatory lesions. The inflammatory polyps are found not only in IBD but also in infectious colitis, ischemic colitis, necrotizing enterocolitis, graft versus host disease, and colonic anastomosis. In non-IBD colitis, inflammatory polyps do not represent a risk factor for CRC.

The association between colonic diverticula and colorectal adenomas and cancer could be related to the epithelial proliferation of colonic mucosa. An upward shifting of cellular proliferation in the colonic mucosa of patients with diverticula was demonstrated and compared with age-matched controls. The cell proliferation index in patients with asymptomatic diverticulosis is three-fold higher than that of healthy controls [76]. It is not clear whether this abnormal epithelial proliferation in colonic diverticula could be responsible for the development of inflammatory polyps, as well as colorectal adenomas and CRC.

In the cohort of patients considered in this study, differences in the frequency of polyps and cancer in patients with diverticulosis, SUDD, SCAD, and diverticulitis have not been detected.

Pathophysiology of diverticulosis is multifactorial, involving genetic predisposition, thickening of the circular and longitudinal muscle wall, elastosis, weakening of the colonic wall, altered neuromuscular activity, environmental factors, age, alteration of microbiota, and inflammation [77,78]. Environmental factors, age, microbiota, and inflammation are also implicated in the pathogenesis of colorectal carcinogenesis [24,79,80,81,82,83].

It has been reported that patients with DD, but also patients with asymptomatic diverticulosis, may display microscopic or macroscopic mucosal signs of mucosal inflammation [25,72]. The relation between chronic inflammation and cancer is well known. Patients with IBD have a significantly higher risk of developing CRC than unaffected subjects, a risk that increases with the extension and duration of the disease [82,83,84]. Furthermore, the epithelial hyper-proliferation of colon crypts, observed both in DD and asymptomatic diverticulosis [85], could be a potential cellular mechanism, leading to a possible increased risk of developing adenomas and CRC in patients with colonic diverticula. It is important to assess whether this increased risk of colorectal adenomas and cancer is linkable to colonic diverticula in general or only to chronic diverticulitis or diverticula with specific genetic and epigenetic variants.

On the other hand, some studies have hypothesized a protective effect of diverticula on CRC development [44]. It should also be noted that not all forms of chronic inflammation of the colon are associated with an increased risk of CRC. Recently, it was reported that microscopic colitis, chronic colitis with the same incidence and prevalence as IBD, appeared to show a reduced risk of adenomas and CRC [86,87].

However, our study shows, some limitations. As this was a cross-sectional study, it was not possible to establish the causal relationship between DD and neoplasm, as well as the future risk of developing CRC in patients with diverticulosis.

Moreover, the indication of a surveillance colonoscopy for a history of polyps was largely self-reported by the patient. Similarly, familial history of CRC and colonic diverticula were also self-reported by patients.

An additional possible limitation is represented by the non-systematic use of validated scales, reporting the extent of diverticulosis and inflammation, or the Paris classification, as the aim of the study focused on histologic findings.

Finally, results involving patients with cancer may be hampered by the limited number of CRCs detected in our study.

However, with the aforementioned limitations, the importance of our study derives not only from being a prospective study including a homogenous population of Caucasian patients but also from a detailed endoscopic localization of diverticula, polyps, and cancers in the various tracts of the large bowel and a histological definition of the various types of polyps and cancer detected.

5. Conclusions

Diverticula and adenomas are frequently found during colonoscopies in adult and elderly patients; however, the evidence of the association between these two conditions is still conflicting.

In our cohort of Caucasic patients, colonic diverticula and colorectal polyps resulted in a significant association, more so for colorectal adenomas and cancer. This finding suggests that patients with colonic diverticula, harboring a higher risk for dysplastic lesions, could require more vigilant endoscopic surveillance than the general population.

However, the present study was not designed to assess follow-up risk. Thus, further prospective large-scale population studies with a long follow-up are needed to corroborate the evidence supporting the relationship between colonic diverticula and colorectal adenomas and CRC, as well as to determine the best time interval between endoscopic examinations.

Author Contributions

Conceptualization, G.L.; design, G.L.; Supervision, G.L. and A.V.; data curation, A.V., F.C., F.V., D.G., G.V., G.S., and A.C.; data analysis and interpretation, S.N., A.V., H.A., and G.L.; writing, A.V. and G.L. All authors have read and agreed to the published version of the manuscript.

Funding

No financial support was received for this study.

Institutional Review Board Statement

The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Review Board of the University of L’Aquila, 67100 L’Aquila, Italy (Protocol Number: 43958).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

No additional data are available.

Conflicts of Interest

The authors declare no conflict of interest.

Footnotes

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