Routine colonoscopy may be needed for uncomplicated acute right colonic diverticulitis

doi:10.21203/rs.2.22488/v2

BACKGROUND: Routine colonoscopy is recommended to determine the coexistence of colon cancer after medical treatment for colon diverticulitis. However, in the case of uncomplicated diverticulitis diagnosed by computed tomography imaging, the clinical relevance of routine follow-up colonoscopy has recently been debated. Yet, the role of follow-up colonoscopy for right colon diverticulitis, which tends to develop at a younger age than left colon diverticulitis, has not been specifically evaluated. Therefore, our aim in this study was to evaluate the incidence of right colon cancer or colonic adenomatous polyps, detected by routine colonoscopy, after conservative management of acute uncomplicated right colon diverticulitis.

METHODS: Included were patients with uncomplicated right colon diverticulitis diagnosed by computed tomography imaging, between 2011 and 2017, and who underwent follow-up colonoscopy surveillance after treatment. The primary outcome was the incidence of colon cancer, with the detection rate of adenoma being the secondary outcome. Information for analysis was retrieved, retrospectively, from patients’ medical records.

RESULTS: The study group included 330 consecutive patients, with a mean age of 41.9 years, and 51.9% being men. For the primary outcome, the rate of colon cancer on follow-up colonoscopy was 0.3% (1/330 cases). The rate of adenoma detection was 20.9% (69/330 cases), with advanced adenoma, including colon cancer, observed in 9 patients (2.7%).

CONCLUSION: In patients with acute uncomplicated right colonic diverticulitis, routine colonoscopy after conservative treatment may be necessary because although the colon cancer detection rate is low, it is possible to detect advanced colon adenoma.

Gastroenterology & Hepatology

Diverticulitis

Acute diverticulitis

Colonic evaluation

Endoscopy

Colonoscopy

Colonic neoplasia

The prevalence of diverticular disease has increased, both the in East and West, due to a lack of dietary fiber intake [1]. In contrast to complicated diverticulitis, which requires surgical treatment, uncomplicated acute diverticulitis can improve with conservative management, with colonoscopy recommended to identify accompanying disease, such as cancer [2]. Yet, a review article reported a low rate of cancer diagnosis during colonoscopy surveillance in patients treated for uncomplicated diverticulitis, with 1 case of cancer among the 67 cases included in the analysis [3]. However, these statistics are based solely on cases with left colon diverticulitis and only a small number of patients (67 patients) were included. As such, the likelihood of cancer among patients treated with uncomplicated right colon diverticulitis is unknown. This knowledge, however, would be important as right-sided colon diverticulitis tends to occur at a younger age than left-sided colon diverticulitis, with a low stage Hinchey classification being common on computed tomography (CT) [4]. Generally, the American Cancer Society guideline recommends colonoscopy surveillance to begin at the age of 45 years [5]. Moreover, the onset of colon cancer at a younger age is more likely to occur in the left than right colon [6]. Considering these points, it is unclear how routine colonoscopy evaluation after right colon diverticulitis could be of clinical benefit with regard to diagnostic performance and economic burden.

Of the literature published on the effects of routine colonoscopy after the treatment of uncomplicated colon diverticulitis, few articles have exclusively included patients with right colon diverticulitis. Thus, the aim of our study was to evaluate the incidence of right colon cancer and colonic adenomatous polyps by routine colonoscopy, after conservative management of acute uncomplicated right colon diverticulitis.

We retrospectively reviewed the electronic medical records of patients diagnosed with acute right-sided colon diverticulitis, between January 2011 and December 2017, at our hospital.

Patients with acute uncomplicated diverticulitis confirmed by CT, were included. Acute uncomplicated diverticulitis was defined, in accordance with previous studies [7, 8], as the presence of colonic diverticular disease with localized colonic wall thickening and/or stranding of pericolonic fat. CT images with appearances of complicated diverticulitis (defined as the presence of pericolonic or abdominal abscess, localized or free extraluminal gas or contrast, obstruction or fistula formation) or the presence of an associated mass lesion were excluded. Follow-up colonoscopy was performed after improvement in the signs of inflammation corresponding to acute diverticulitis, with the consent of the patient. Exclusion criteria were as follows: complicated diverticulitis; accompanying left colon cancer; patients who underwent emergency surgery; and patients in whom follow-up colonoscopy was not performed or was not consented to. The reasons why a patient did not undergo colonoscopy was investigated based on a previous paper [9].

The following colonoscopy findings were documented: hyperplastic polyp, adenoma (including advanced adenoma), and carcinoma. Patients with polyps detected in the right colon were the focus of our analysis. Advanced adenoma was defined as either an adenoma of 10 mm or greater in diameter and/or more than 25% villous components and/or severe dysplasia [10]

The primary outcome was the detection rate of colon cancer, confirmed by pathological diagnosis, on follow-up colonoscopy. The secondary outcome was the detection rate of hyperplastic polyp and adenoma on follow-up colonoscopy.

Statistical analysis

Categorical variables were reported as a count (and associated percentage, %), with continuous variables reported as the median and interquartile range (IQR). We compared the characteristics of patients for whom colonoscopy was not performed with those who underwent colonoscopy to ensure that patients included in our study group were representative of the entire sample. To compare the group with and without colonoscopy, the chi-squared or Fisher exact test was used for categorical variables, as appropriate. As such, between-group comparisons of continuous variables were evaluated using the Mann-Whitney test. Additionally, among patients who underwent a colonoscopy, we evaluated the difference in the frequency of polyp detection between patients <45 years and ≥45 years of age using the chi-squared or Fisher’s exact tests, as appropriate.

All analyses were performed using SPSS (version 21, IBM, NY, USA).

A total of 668 consecutive patients were diagnosed with acute right colon diverticulitis, by CT, over the period of observation of the study. From these, the following patients were excluded from the analysis: 47 who had complicated diverticulitis; 1 with sigmoid colon cancer simultaneously diagnosed on CT imaging; and 1 who underwent emergency surgery because symptoms did not improve. Of the remaining 619 patients, follow-up colonoscopy was performed in 330 (Fig 1). Follow-up colonoscopy was performed at a median of 32 days (IQR, 25-42 days) after recovery from acute diverticulitis.

Clinical characteristics of patients included in the analysis are reported in Table 1, with salient characteristics as follows: median age, 40 (IQR, 33-49) years; male, 59.7%; and predominant involvement of the cecum (48.3%) and ascending colon (49.9%). With regard to clinical factors, only the length of hospital stay was significantly different between the two groups.

On follow-up colonoscopy, hyperplastic polyps were identified in 30 patients (9.1%) and adenomas in 69 patients (20.9%), with evidence of high-grade dysplasia in 2 of these cases. Villous adenoma was detected in 1 case. An advanced adenoma, including colon cancer, was observed in 9 patients (2.7%), one of whom was diagnosed with ascending colon cancer. Polyps were found in the right colon in 46 of 87 patients with colon polyps (Table 2). Additionally, on biopsy, chronic inflammation of the right colon was confirmed in 13 patients: erythematous mucosal change (n=5) or ulceration (n=8). Furthermore, colonic diverticuli were found in 79.1%

(261/330) of patients who underwent colonoscopy. There was no incidence of inflammatory bowel disease combined with diverticulosis.

Ascending colon cancer was confirmed by pathological examination in one male patient in his late 40s, who sought consultation at our emergency department owing to a 2-day history of abdominal pain. He was admitted and treated with a 5-day course of intravenous antibiotics. CT examination, performed by an expert radiologist, revealed a segmented cecum and thickening of the wall of the ascending colon, with perilesional fat infiltration. Follow-up colonoscopy was performed 6 weeks after imaging, with a diagnosis of ascending colon cancer confirmed.

Among patients with uncomplicated diverticulitis (n=330) who underwent colonoscopy, recurrence occurred in 30 patients (9.1%), over a median follow-up period of 680.1 days. Surgery was performed in 5 of these patients (1.5%), for recurrent diverticulitis in 4 patients and for the aforementioned cancer in the remaining 1 patient).

The reasons for lack of follow-up colonoscopy are summarized in Table 3. Mainly, 103 patients (35.6%) were scheduled for colonoscopy which was not yet performed for unknown reasons; 86 patients (29.8%) were lost to follow-up; 22 patients (7.8%) had a history of a recent prior colonoscopy; 15 (5.3%) underwent follow-up colonoscopy at another hospital; and 10 (3.5%) were followed up using colon barium study at the patient's request.

Since the frequency of polyp detection may vary according to age, we analyzed 330 patients who underwent colonoscopy into over 45 and under 45 years of age. As a result, hyperplastic polyp (14.9% vs 5.7%, p=0.005) and low grade dysplasia (33.9% vs 12.4%, p<0.001) were found more frequently in the age of 45 years and over. Most of all, the rate of advanced adenoma detection was statistically significantly higher in those aged 45 years or older than those under 45 years old. (5.8% vs 1.0%, p=0.009) (table 4).

The incidence rate of colon cancer detected by routine colonoscopy performed after conservative treatment of right colon acute uncomplicated diverticulitis was low at 0.3% (1/330 cases). The detection rate of adenoma in the whole colon was 20.9% and the frequency of advanced adenoma was 2.7%.

Clinically, the features of right colon diverticulitis are different from those of left colon diverticulitis. Specifically, compared to left colon diverticulitis, right colon diverticulitis tends to occur at a younger age, with a lower Hinchey stage, and a lower rate of recurrence (3.1% versus 17.9% for left colon diverticulitis) [11]. Based on these facts, and considering the high diagnostic yield of CT imaging and the development of accurate pathological finding for colon cancer, the utility of routine colonoscopy in patients after treatment of acute right colon diverticulitis, in the absence of complications, such as perforation, abscess formation, and/or obstruction, has been questioned [12]. It has also been questioned if the incidence of colorectal cancer at younger ages is indeed more common on the left than on the right colon [6].

Several studies have been published on the effects of routine colonoscopy after conservative treatment of acute uncomplicated diverticulitis. Among 205 patients who underwent colonoscopy or CT colonoscopy for all colonic diverticulitis, regardless of the colonic segment involved, Westwood et al. reported a detection rate of 9.3% for adenomas and 0.5% for colorectal cancer [13]. Additionally, Horesh et al. reported a rate of malignant findings of 1.6%, among 310 patients, for all of those with colonic diverticulitis who underwent colonoscopy. Of specific clinical relevance is the finding that there was no incidence of adenocarcinoma of the colon on follow-up colonoscopy after uncomplicated colon diverticulitis among patients younger than 50 years of age [14]. However, the majority of this evidence included only patients with left colon diverticulitis. In fact, to our knowledge, only two previous studies addressed right colon diverticulitis [15, 16] . In their study of 109 patients with right-sided colon diverticulitis, Hashimoto et al. did not identify any cases of colorectal cancer, with a rate of advanced adenoma of 6.4% (7/109 cases) and non-advanced adenoma of 21.1% (23/109 cases) [16]. Chan et al. reported on 27 patients with right colon diverticulitis, with no incidence of colorectal cancer or advanced adenoma identified [15]. However, both of these studies included a small number of patients. By contrast, our study included 330 patients, a relatively large sample size. Similar to previous findings, adenoma and cancer detection rates were very low. Of significance was our finding that adenoma were identified only in the right colon.

According to a previous population-based study evaluating the prevalence of colorectal adenomas in asymptomatic Korean men and women published in 2014 [17], the prevalences of colorectal adenomas and advanced adenomas were 34.5% and 3.1%, respectively. On subgroup analysis, in patients <50 years of age, the adenoma detection rate was 20.6-24.4%, which was comparable to the rate in our study (20.9%). However, the rate of advanced adenoma detection was fairly higher in our study (2.7%) than in this previously reported study (1.1-1.7%). This suggests that patients with right uncomplicated colonic diverticulitis are more likely to have advanced colon adenoma; therefore, routine colonoscopy should be performed for these patients.

The adenoma detection rate (ADR) has been associated with the interval risk of colorectal cancer [18]. The ADR can be used as a colonoscopy quality indicator, with an ADR of <20% being associated with a 10-fold increase in the interval cancer risk [19]. The ADR in our study, which included only patients with right colon diverticulitis, was 20.9%. We consider this rate to be appropriate for our study as our primary outcome was the detection rate of colon cancer.

A previous study reported that complicated diverticulitis is more likely to be associated with colon cancer compared to uncomplicated diverticulitis [9]. Therefore, our study also included patients with complicated diverticulitis, with comparison between patients with complicated and uncomplicated diverticulitis. However, the number of patients with complicated diverticulitis in this study (n=47) was lower than that in the previous study (n=172). Of the 47 patients included in our study group, 8 underwent emergency surgery, and all patients were diagnosed with diverticulitis after surgery. In addition, only 21 of the 39 patients underwent routine colonoscopy, among whom no colon cancer was found (see Supplementary Tables). Therefore, we excluded patients with complicated diverticulitis.

Limitation

The limitations of our study need to be acknowledged. Foremost, this is a retrospective study, with no knowledge of the outcomes of colonoscopy surveillance for patients who did not undergo follow-up colonoscopy. We do note that patients who did not undergo follow-up colonoscopy tended to be younger than those who did undergo colonoscopy follow-up, although there was no statistical significance. Furthermore, among the total of 355 patients (57.7%), including patients who performed follow-up colonoscopy at another hospital and those who underwent colon barium were confirmed that there was no colon cancer. This rate (57.7%) of colonoscopy surveillance is comparable to previously reported rate in review articles [20, 21]. Second, as our study is not a population based, our findings do not provide an estimate of colon cancer incidence in all patients with uncomplicated right colon diverticulitis. However, the strength of our study is the relatively large sample size which, in fact, is the largest study to date evaluating routine colonoscopy results among patients with right colon diverticulitis.

In conclusion, in patients with acute uncomplicated right colonic diverticulitis, routine colonoscopy after conservative treatment may be necessary because it is possible to detect advanced colon adenoma. Especially, for patients under the age of 45 years with a positive family history for colon disease and for those over the age of 45 years who have not undergone colonoscopy within the last 3 years, screening colonoscopy is strongly recommended, which is consistent with published guidelines [5]. It will be necessary to confirm the results of our study by collecting a larger number of patients through a multicenter or population based study.

ADR, adenoma detection rate; CT, computed tomography; IQR, interquartile range

Ethics approval and consent to participate: This study was approved by our hospital’s institutional review board. Owing to the retrospective design of the study, the need for informed consent was waived. The study was conducted according to the principles of the Declaration of Helsinki.

Consent for publication: Not applicable

Availability of data and materials: Not applicable

Competing Interests: None of the authors have any conflict of interest.

Funding: Not applicable

Author Contributions

KYL and JIL designed the study. KYL and YYP collected the data and performed the statistical analysis. KYL, JIL, YYP and STO interpreted the results of the analysis and prepared the manuscript. All authors contributed extensively to the work presented.

Acknowledgements: Not applicable

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Table 1. Clinical characteristics of patients with acute uncomplicated diverticulitis

Variables	Colonoscopy (n=330)	No Colonoscopy (n=289)	p-value
Age (years)	40 (34–50)	40 (31-48)	0.168^*
Sex Male Female	195 (59.1%) 135 (40.9%)	174 (60.2%) 115 (39.8%)	0.778^¶
Height	167.5 (160.0-173.5)	168.0 (160.4-173)	0.962^*
BMI (kg/m²)	23.8 (21.7-26.3)	23.4 (21.6-25.9)	0.135^*
Duration of hospital stay (days)	4 (4-5)	4 (3-5)	0.010^*
Social history Smoking Alcohol	142 (43%)^† 137 (42.7%)^‡	139 (48.1%) 110 (38.1%)^§	0.303^¶ 0.248^¶
Past medical history Hypertension Diabetes	50 (15.2%) 14 (4.2%)	31 (10.7%) 12 (4.2%)	0.103^¶ 0.956^¶
Location of acute diverticulitis Cecum Ascending Hepatic flexure Transverse	154 (46.7%) 171 (51.8%) 3 (0.9%) 2 (0.6%)	144 (49.8%) 139 (48.1%) 3 (1.0%) 3 (1.0%)	0.770^¶
White blood cell count (10³/μL)	11.1 (9.2-12.9)	11.5 (9.7-14.0)	0.082^*
C-reactive protein (mg/dl)	3.5 (1.6-6.5)	3.8 (1.6-7.0)	0.553^*

IQR, interquartile range; BMI, body mass index.

Continuous variables are reported as the median (and IQR)

Categorical variables are reported as a count (and percentage, %)

‡ Missing data: n=1, ‡ Missing data: n=9, §Missing data: n=13

*Mann-Whitney test, **Fisher exact test, ¶chi-squared test

Table 2. Results of colonoscopy examination

Variables	Value
Hyperplastic polyp	30 (9.1%)
Adenoma Low grade dysplasia High grade dysplasia	67 (20.3%) 2 (0.6%)
Villous adenoma	1 (0.6%)
Adenocarcinoma	1 (0.6%)
Advanced adenoma	9 (2.7%)
Right-sided polyp†	46 (52.9%) ^†

† number (%) of patients in whom polyps were detected in the right colon among those with a detected adenoma (total number of patients, 87)

Table 3. Reasons for patients to not undergo colonoscopy

Reasons	Number (%)
Prior colonoscopy ≤12 months prior	15 (5.2%)
12 < Prior colonoscopy ≤ 24 months	3 (1.0%)
24 < Prior colonoscopy ≤ 36 months	1 (0.3%)
36 < Prior colonoscopy ≤ 60 months	2 (0.7%)
60 < Prior colonoscopy ≤ 120 months	1 (0.3%)
Patient declined	12 (4.2%)
Lost to follow-up	86 (29.8%)
Patient frailty	2 (0.7%)
No recommendation by treating team	12 (4.2%)
Not scheduled, reason unknown	25 (8.7%)
Colonoscopy scheduled, but have not had the procedure owing to unknown cause	103 (35.6%)
Colonoscopy performed at another hospital	15 (5.2%)
Double-contrast barium enema only performed	10 (3.5%)
Death prior to colonoscopy	1 (0.4%)

Table 4. Comparison of polyp detection during routine colonoscopy between patients under and over 45 years old

Variables	Under 45 (n=209)	Over 45 (n=121)	p-value
Hyperplastic polyp	12 (5.7%)	18 (14.9%)	0.005
Adenoma Low grade dysplasia High grade dysplasia	26 (12.4%) 0 (0%)	41 (33.9%) 2 (1.7%)	<0.001 0.134
Adenocarcinoma	0 (0%)	1 (0.8%)	0.368
Advanced adenoma	2 (1.0%)	7 (5.8%)	0.009

Tablesupplement.docx

Routine colonoscopy may be needed for uncomplicated acute right colonic diverticulitis

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Abstract

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Background

Methods

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Discussion

Abbreviations

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