J Neurogastroenterol Motil 2024; 30(1): 87-96  https://doi.org/10.5056/jnm22162
The Prevalence and Characteristics of Symptomatic Uncomplicated Diverticular Disease Among Asian Patients With Unexplained Abdominal Symptoms
Tsumugi Jono,1,2 Yuki Kasai,1 Takaomi Kessoku,1,3,4 Tomoki Ogata,1 Kosuke Tanaka,1,3 Tsutomu Yoshihara,1 Noboru Misawa,1 Shingo Kato,1,5 Takuma Higurashi,1 Kunihiro Hosono,1 Masato Yoneda,1 Kosuke Seita,6 Takayuki Kato,6 Eiji Sakai,2 Takeo Kurihashi,7 Machiko Nakatogawa,8 Shunsuke Oyamada,9 Seiji Futagami,10 Kok-Ann Gwee,11 and Atsushi Nakajima1*
1Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine Graduate School of Medicine, Yokohama, Japan; 2Department of Gastroenterology, Yokohama Sakae Kyosai Hospital, Yokohama, Japan; Department of 3Palliative Medicine and 4Gastroenterology, International University Health and Welfare Narita Hospital, Narita, Japan; 5Departments of Clinical Cancer Genomics, Yokohama City University Hospital, Yokohama, Japan; 6Department of Gastroenterology, International University of Health and Welfare Atami Hospital, Atami, Japan; 7Department of Internal Medicine, Kanagawa Dental University Yokohama Clinic, Yokohama, Japan; 8Department of Internal Medicine, Namiki Koiso-Medical Clinic, Yokohama, Japan; 9Department of Biostatistics, JORTC Data Center, Tokyo, Japan; 10Division of Gastroenterology, Nippon Medical School, Tokyo, Japan; and 11Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Correspondence to: *Atsushi Nakajima, MD, PhD
Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan
Tel: +81-45-787-2640, E-mail: nakajima-tky@umin.ac.jp

Tsumugi Jono, Yuki Kasai, and Takaomi Kessoku contributed equally to this study.
Received: September 20, 2022; Revised: April 2, 2023; Accepted: May 11, 2023; Published online: November 28, 2023
© The Korean Society of Neurogastroenterology and Motility. All rights reserved.

cc This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background/Aims
The precise incidence of symptomatic uncomplicated diverticular disease (SUDD) and its effects on the quality of life (QOL) remain unclear, particularly in Asian patients with right-sided SUDD. We assess the prevalence of SUDD and its impact on QOL in a real-world population.
Methods
Five institutional cohorts of patients who received outpatient treatment for unexplained abdominal symptoms from January 15, 2020 to March 31, 2022, were included. All patients underwent colonoscopy. SUDD was defined as the presence of recurrent abdominal symptoms, particularly pain in the lower right or left quadrant lasting > 24 hours in patients with diverticulosis at the site of pain. The 36-item short-form health survey was used to assess QOL.
Results
Diverticula were identified in 108 of 361 patients. Among these 108 patients, 31% had SUDD, which was right-sided in 39% of cases. Of the 50 patients with right-sided diverticula, 36% had SUDD, as did 15 of 35 patients with left-sided diverticula (43%). Among the 33 patients with SUDD, diverticula were right-sided, left-sided, and bilateral in 39%, 45%, and 15% of patients, respectively. Diarrhea was more frequent in the SUDD group than in the non-SUDD group. Patients with SUDD had significantly lower physical, mental, and role/social component scores than those without SUDD.
Conclusions
It is important to recognize that patients with SUDD account for as high as 31% of outpatients with unexplained abdominal symptoms; these patients have diarrhea and a low QOL. The presence of right-sided SUDD was characteristic of Asian patients.
Keywords: Diverticulosis; Quality of life; Symptomatic uncomplicated diverticular disease
Introduction

Diverticulosis is characterized by the presence of diverticula within the colon, which manifests as bulging herniations of the mucosa and submucosa.1 Diverticula form because of chronic constipation, increased intestinal pressure during defecation due to a Western diet with high meat and fat intake and low fiber intake, and age-related deterioration of the intestinal wall.

Although diverticulosis represents the most frequent anatomical alteration of the colon, the distribution of diverticula throughout the colon exhibits marked geographic variations. In Asia, it is reported to be 12.5% in Korea and 70.1% in Japan; in Europe, it is the lowest in Romania (2.5%) and the highest in Italy (51.4%). In Western countries, diverticulosis is detected 90% of the time in the sigmoid colon or left colon, whereas in Japan and Korea, it is more common (75-85%) in the ascending or right colon.2

In most cases, diverticulosis is asymptomatic. Abdominal pain that may be related to the presence of diverticula is called diverticular disease (DD). Symptomatic diverticulosis without complications is termed symptomatic uncomplicated diverticular disease (SUDD).3 SUDD is associated with persistent pain, leading to a decline in the patient’s quality of life (QOL) and a high incidence of acute diverticulitis, which requires treatment; however, the mechanisms underlying its pathogenesis remain to be elucidated. Despite interest in this disease and previous reports of left-sided SUDD, the true prevalence of SUDD in Asia remains unknown, especially for cases affecting the right side.4 Therefore, this study aims to clarify the epidemiological characteristics of SUDD, especially right-sided SUDD, and its impact on QOL.

Materials and Methods

Study Participants

A prospective cohort study design was employed. This study included 5 institutional cohorts of patients referred to outpatient clinics (Yokohama City University Hospital, Kanagawa Dental University Yokohama Clinic, International University of Health and Welfare Atami Hospital, Yokohama Sakae Kyosai Hospital, and Namiki Koiso Clinic) for unexplained abdominal symptoms from February 6, 2021 to May 31, 2022. The study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the local ethics committee of Yokohama City University Hospital (October 15, 2020; approval number: B200800055). The study was registered with the University Hospital Medical Information Network (UMIN000043262) on February 5, 2021. Informed consent was obtained from all participants prior to enrollment.

Patients with chronic abdominal symptoms were considered to have unexplained abdominal symptoms when they had attended gastroenterology clinics at least 3 times during a 6-month period and failed to obtain a diagnosis despite undergoing various tests. Patients were examined at outpatient clinics specializing in the diagnosis of chronic abdominal symptoms to rule out organic diseases such as inflammatory bowel disease or colorectal cancer. All patients underwent colonoscopy, and the presence and site of diverticulosis were assessed. Colonoscopy findings were double-checked by expert colonoscopists. Questionnaires were used to investigate age, sex, body mass index (BMI), waist circumference, history of laparotomy, subjective symptoms, and pain level. A dietary survey was conducted by means of a questionnaire, wherein the first question asked whether the diet was mainly Western diet or Japanese diet, and the second question asked whether the diet was mainly a meat, fish, vegetable, or well-balanced diet. The severity of abdominal pain was assessed using an 11-point numerical rating scale, with 0 representing no pain and 10 representing the most severe pain.5 SUDD was defined as follows: (1) the presence of recurrent abdominal symptoms, specifically pain in the right or left lower quadrant lasting > 24 hours, without signs, symptoms, laboratory findings, and/or macroscopic evidence indicating acute diverticulitis; (2) absence of any other complications (stenosis, abscesses, or fistulas); and (3) not fulfilling the criteria for irritable bowel syndrome (IBS).6 In this study, IBS was defined per the Rome IV criteria.7 Non-SUDD patients were those who had diverticula but did not meet the definition of SUDD. Patients with post-diverticulitis SUDD (PD-SUDD) had experienced at least 1 episode of acute diverticulitis with or without complications and had abdominal pain primarily in the lower abdomen despite the resolution of macroscopic findings of diverticulitis.1

Defecation Record Analysis

Stool consistency was scored using the Bristol stool form scale (BSFS), which includes the following 7 different categories for evaluating the shape of stool: types 1 and 2 indicate constipation; types 3 and 4 indicate normal defecation; and types 5, 6, and 7 indicate diarrhea.8

Diverticula Inflammation and Complications Assessment Score

Developed and validated in 2015, the Diverticula Inflammation and Complications Assessment (DICA) score represents the first endoscopic classification of diverticulosis.9 The DICA considers several factors, including the extension of diverticulosis, number of diverticula in each region, presence of inflammatory signs, and occurrence of complications.10 Whether the disease had affected the left or right colon was referred to as diverticulosis extension. Diverticulosis in the left colon was given 2 points because in Western cultures, the left colon experiences more diverticulosis (and hence, more diverticulitis) than the right colon. In contrast, the diverticulosis in the right colon received 1 point. Each region’s diverticula count was ranked as follows: up to 15 (grade I: 0 points) and > 15 (grade II: 1 point). Inflammation was evaluated by assigning 1 point to edema/hyperemia, 2 points to erosions, and 3 points to segmental colitis. The most severe grade of inflammation was noted when different levels of inflammation were found. Complications, including rigidity of the colon (eg, poor distension of the diverticular district caused by inflation, mild stenosis allowing a standard colonoscope to pass through the narrowed lumen, moderate-to-severe stenosis preventing passage of a standard colonoscope, and a narrowed lumen with a high risk of perforation because of anatomical features such as the presence of multiple diverticula at the splenic flexure), the presence of purulent material exiting the diverticular opening, and bleeding, were assessed. DICA scores were divided into 3 categories: DICA 1 (up to 3 points) reflecting simple diverticulosis, DICA 2 (4 to 7 points) reflecting conditions ranging from severe diverticulosis to milder diverticulitis, and DICA 3 (more than 7 points) reflecting more severe diverticulitis or complications following diverticulitis (ie, stenosis).11 DICA scores may be related to the severity of abdominal pain, erythrocyte sedimentation rate, and C-reactive protein (CRP) levels, according to a prior study.11

Quality of Life Analysis

The 36-item short-form health survey (SF-36) includes 8 subscales designed to assess physical function, social functioning, role limitations due to physical problems, role limitations due to emotional problems, mental health, vitality, pain, and general health perception.12 Scores across these eight subscales are used to calculate summary scores for 3 components: physical component summary (PCS), mental component summary (MCS), and role/social component summary (RCS). The total score for each summary of the SF-36 ranges from 0 to 100, with higher scores indicating better health-related QOL.13

The Patient Assessment of Constipation Quality of Life Questionnaire (PAC-QOL) is a trustworthy, specific, self-administered questionnaire developed and validated to evaluate QOL impairment in patients with chronic constipation.14 This study utilized the Japanese version of the PAC-QOL (JPAC-QOL);15 28 items on this scale were rated on a 5-point Likert scale (0 = not at all; 1 = slightly; 2 = moderately; 3 = quite a bit; and 4 = extremely or a great deal). The PAC-QOL score consists of 4 subscales: physical discomfort, psychosocial discomfort, worries/concerns, and satisfaction. Average scores were used to express the overall and each subscale results.15

The Patient Assessment of Constipation-Symptoms (PAC-SYM) questionnaire, developed through psychometric evaluation of adults with chronic constipation, is a key tool for evaluating the severity of patient-reported symptoms of this illness. The 12-item questionnaire was divided into 3 symptom subscales: abdominal (4 items), rectal (3 items), and stool (5 items). Items were scored on 5-point Likert scales, with scores ranging from 0 to 4 (0 = symptom absent; 1 = mild; 2 = moderate; 3 = severe; and 4 = very severe). By dividing the total score by the number of items answered, a mean total score of 0-4 was computed, with lower total scores denoting a reduced symptom burden.16

Blood and Stool Test

High-sensitivity CRP (hsCRP) was measured using standard methods at each institution, and fecal calprotectin was measured in accordance with the manufacturer’s instructions (HK382; Hycult Biotech Inc, Wayne, PA, USA).

Statistical Methods

Data were analyzed using the JMP 15.0 software (SAS Institute Inc, Cary, NC, USA) and are expressed as the mean ± standard deviation unless indicated otherwise. Student’s t test was used for the univariate comparison of means or continuous variables between the 2 groups, while a one-way analysis of variance across the 3 groups was performed with the calculation of the P-value for the F-test. If the P-value for the F-test was significant at a two-sided significance level of 5%, then two-sample t tests were performed for all 3 pairwise comparisons across the three groups, according to Fisher’s least significant difference post hoc test to adjust for multiple testing. Binary variables were compared using the χ2 test. All t tests, F-tests, and χ2 tests were two-sided with a significance level of 5% (P < 0.05). GraphPad Prism 7 (GraphPad Software, Inc, La Jolla, CA, USA) was used to create the figures, and the data are described as mean and standard error.

Results

Patient Characteristics

In total, 361 patients with abdominal symptoms were evaluated (mean age: 59 years, 42% men, mean BMI: 22.3 kg/m2, mean waist circumference: 80.8 cm), of whom 32% had previously undergone laparotomy. Two hundred fifty-three patients without diverticulosis were excluded: 54 patients with chronic intestinal pseudo-obstruction, 128 with functional constipation, 12 with functional diarrhea, and 25 with IBS. The 108 patients with diverticulosis with unexplained abdominal symptoms enrolled in the study were comprised of 63% male patients and 29% patients who had previously undergone laparotomy; they had a mean age of 64 years, had a mean BMI of 24.6 kg/m2, and had a mean waist circumference of 86 cm (Fig. 1 and Table 1). The average number of months from surgery to the first visit was 312 (11-876) months. Therefore, cases immediately after laparotomy were not included in this study.

Figure 1. Flowchart of patient selection and prevalence of symptomatic uncomplicated diverticular disease (SUDD) in patients with diverticulosis with unexplained abdominal symptoms. CIPO, chronic intestinal pseudo-obstruction; IBS, irritable bowel syndrome.

Table 1 . Demographic in Patients With Diverticulosis With Unexplained Abdominal Symptoms

VariablesDiverticulosisa (n = 108)
Age (yr)64 ± 11
Male64 (63)
BMI (kg/m2)24.6 ± 4.5
Waist circumference (cm)86 ± 12
History of laparotomy30 (28)

aDiverticulosis with unexplained abdominal symptoms.

BMI, body mass index.

Data are shown in mean ± SD or n (%).



Prevalence of Diverticulosis With Unexplained Abdominal Symptoms, Diverticular Disease, and Symptomatic Uncomplicated Diverticular Disease

Of the 361 total patients, 30% (108) had diverticulosis with unexplained abdominal symptoms, 16% (59) had DD, and 9% (33) had SUDD (Fig. 2A). Among the 108 patients with diverticulosis with unexplained abdominal symptoms, 55% (59) had DD, and 31% (33) had SUDD (Fig. 2B). The percentage of patients with a history of diverticulitis among the 33 patients with SUDD was 30% (10), and none of these patients had a history of complicated diverticulitis. Among the patients without diverticulum, 25 (10%) had IBS, among the Non-SUDD patients, 3 (4%) had IBS, and there was no overlap between SUDD and IBS. Diverticulosis was right-sided, left-sided, and bilateral in 50, 35, and 23 patients, respectively. Among the 50 patients with right-sided diverticula, 46% (23) had DD and 26% (13) had SUDD (Fig. 2C). Among the 35 patients with left-sided diverticula, 66% (23) had DD and 43% (15) had SUDD (Fig. 2D). Among the 33 patients with SUDD, 39% (13) cases were right-sided, 45% (15) cases were left-sided, and 15% (5) cases were bilateral (Fig. 2E).

Figure 2. Prevalence of diverticulosis with unexplained abdominal symptoms, diverticular disease (DD), or symptomatic uncomplicated diverticular disease (SUDD) (N = 361). (A) Breakdown of participants. (B) Breakdown of patients with diverticulosis. (C) Breakdown of patients with diverticulosis in right side. (D) Breakdown of patients with diverticulosis in left side. (E) Breakdown of SUDD patients by diverticulum site.

Subjective Symptoms in Patients With Diverticulosis With Unexplained Abdominal Symptoms, Diverticular Disease, and Symptomatic Uncomplicated Diverticular Disease

Of the patients with diverticulosis with unexplained abdominal symptoms, 55% (59) had abdominal pain, 28% (30) had constipation, 33% (36) had diarrhea, and 19% (21) had abdominal bloating. Among patients with DD, 34% (20) had constipation, 44% (26) had diarrhea, and 29% (17) had abdominal bloating (Table 2). Of the patients with SUDD, 24% (8) had constipation, 48% (16) had diarrhea, and 24% (8) had abdominal bloating (Table 2). The SUDD group had a significantly higher frequency of abdominal pain and diarrhea symptoms than the non-SUDD group (abdominal pain: non-SUDD 35% vs SUDD 100%, P < 0.001; diarrhea: non-SUDD 27% vs SUDD 48%, P = 0.027. However, rates of bloating and constipation did not significantly differ between the SUDD and non-SUDD groups (bloating: non-SUDD 17% vs SUDD 24%, P = 0.403; constipation: non-SUDD 29% vs SUDD 24%, P = 0.586).

Table 2 . Symptoms of Diverticulosis With Unexplained Abdominal Symptoms or Diverticular Disease or Symptomatic Uncomplicated Diverticular Disease or Non-symptomatic Uncomplicated Diverticular Disease

SymptomsDiverticulosisa (n = 108)DD (n = 59)SUDD (n = 33)Non-SUDD (n = 75)P-value
SUDD vs Non-SUDD
Abdominal pain59 (55)59 (100)33 (100)26 (35)< 0.001
Abdominal bloating21 (19)17 (29)8 (24)13 (17)0.403
Constipation30 (28)20 (34)8 (24)22 (29)0.586
Diarrhea36 (33)26 (44)16 (48)20 (27)0.027

aDiverticulosis with unexplained abdominal symptoms.

DD, diverticular disease; SUDD, symptomatic uncomplicated diverticular disease.

Data are shown in n (%).



Symptomatic Uncomplicated Diverticular Disease Characteristics and Defecation-specific Quality of Life

Table 3 presents the characteristics of patients in the SUDD and non-SUDD groups. Patients with SUDD had significantly fewer prior laparotomies than those without SUDD (16% vs 35%, respectively; P = 0.044), suggesting that previous surgery was not the cause of SUDD. No significant between-group differences in age, sex, body size, or diet were observed. BSFS scores were significantly higher in the SUDD group than in the non-SUDD group (non-SUDD 3.8 vs SUDD 5.5, P < 0.001). The number of patients with a BSFS score of 6 or 7 was also significantly higher in the SUDD group than in the non-SUDD group (non-SUDD 12% vs SUDD 63%, P < 0.001). Numerical rating scale scores were significantly higher in the SUDD group than in the non-SUDD group (non-SUDD 3.6 vs SUDD 5.8, P < 0.001).

Table 3 . Differences of Characteristics, Quality of life, and Symptom Scores Between Non-symptomatic Uncomplicated Diverticular Disease and Symptomatic Uncomplicated Diverticular Disease

VariablesNon-SUDD (n = 75)SUDD (n = 33)P-value
Age (yr)65 ± 1162 ± 140.165
Male48 (68)16 (52)0.124
BMI (kg/m2)25 ± 524 ± 40.166
Waist circumference (cm)88 ± 1383 ± 100.174
Western diet20 (27)8 (24)0.791
Japanese diet34 (45)18 (55)0.378
Meat diet16 (21)8 (24)0.738
Fish diet9 (12)2 (6)0.347
Vegetable diet4 (5)3 (9)0.465
Well-balanced diet33 (44)13 (39)0.656
History of laparotomy25 (35)5 (16)0.044
Severity of abdominal pain3.6 ± 2.05.8 ± 2.4< 0.001
Stool form
BSFS3.8 ± 1.45.5 ± 1.1< 0.001
Proportion of BSFS 6+79 (12)21 (64)< 0.001
DICA classification
Diverticular location1.5 ± 0.51.6 ± 0.50.345
Number of diverticula0.1 ± 0.30.8 ± 0.4< 0.001
Inflammations00
Complications00
DICA total point1.6 ± 0.62.4 ± 0.6< 0.001
DICA 1: 1-3 points75 (100)33 (100)
DICA 2: 4-7 points00
DICA 3: > 7 points00
Blood test
hsCRP (mg/dL)0.1 ± 0.10.4 ± 0.2< 0.001
hsCRP (> 0.3 mg/dL)5 (7)25 (76)< 0.001
Fecal test
Calprotectin (μg/g)16 ± 1446 ± 29< 0.001
Calprotectin (> 15 μg/g)20 (27)26 (79)< 0.001
SF-36
PCS46 ± 1538 ± 120.009
MCS49 ± 1143 ± 100.012
RCS39 ± 1830 ± 140.010
JPAC-QOL
Overall0.4 ± 0.20.9 ± 0.3< 0.001
Physical discomfort0.4 ± 0.40.3 ± 0.30.195
Psychosocial discomfort0.2 ± 0.20.4 ± 0.2< 0.001
Worries/concerns0.3 ± 0.20.8 ± 0.4< 0.001
Satisfaction0.8 ± 0.52.1 ± 0.7< 0.001
PAC-SYM
Overall0.5 ± 0.31.0 ± 0.4< 0.001
Stool symptom0.2 ± 0.30.2 ± 0.30.564
Rectal symptom0.2 ± 0.20.2 ± 0.30.455
Abdominal symptom0.9 ± 0.72.2 ± 0.9< 0.001

SUDD, symptomatic uncomplicated diverticular disease; BMI, body mass index; BSFS, Bristol stool form scale; DICA, Diverticular Inflammation and Complication Assessment; hsCRP, high sensitivity C reactive protein; SF-36, 36-item short-form health survey; PCS, physical component summary; MCS, mental component summary; RCS, role/social component summary; JPAC-QOL, Japanese version of the patient assessment of constipation quality of life; PAC-SYM, Patient Assessment of Constipation-Symptoms.

Data are shown in mean ± SD, n (%), or n.



The total DICA classification score was significantly higher in the SUDD group than in the non-SUDD group (non-SUDD 1.6 vs SUDD 2.4, P < 0.001). Blood levels of hsCRP were also significantly higher in the SUDD group than in the non-SUDD group (non-SUDD: 0.13 ± 0.11, SUDD: 0.42 ± 0.20, P < 0.001) (Supplementary Fig. 1A). On setting the cutoff value of blood hsCRP to 0.3 mg/dL,17 CRP-positive cases comprised 25 (76%) SUDD cases and 5 (7%) non-SUDD cases (P < 0.001). Fecal calprotectin levels were significantly higher in the SUDD group (non-SUDD: 16 ± 14, SUDD: 46 ± 29, P < 0.001) (Supplementary Fig. 1B). On setting the cutoff value of fecal calprotectin to 15 μg/g,18 calprotectin-positive cases comprised 26 (79%) SUDD cases and 20 (27%) non-SUDD cases (P < 0.001).

The QOL analysis revealed that patients in the SUDD group had significantly lower PCS, MCS, and RCS scores on the SF-36 than those in the non-SUDD group (PCS: non-SUDD 45.8 vs SUDD 38.0, P = 0.009; MCS: non-SUDD 48.7 vs SUDD 43.0, P = 0.012; RCS: non-SUDD 39.0 vs SUDD 30.0, P = 0.010) (Table 4 and Supplementary Fig. 2). Overall, PAC-QOL scores were significantly higher in the SUDD group than in the non-SUDD group (non-SUDD 0.4 vs SUDD 0.9, P < 0.001), as were subscale scores for psychosocial discomfort, worries/concerns, and satisfaction (Table 3). Overall, PAC-SYM scores were also significantly higher in the SUDD group than in the non-SUDD group (non-SUDD 0.5, vs SUDD 1.0, P < 0.001) (Table 3).

Table 4 . Characteristics and Quality of Life of Symptomatic Uncomplicated Diverticular Disease Patients by Site of Diverticulum Presence

VariablesR (n = 13)L (n = 15)B (n = 5)P-valueP-value
for F testR vs LR vs BL vs B
Age (yr)63 ± 1561 ± 1361 ± 150.950
Male4 (31)10 (77)2 (40)0.0180.710.137
BMI (kg/m2)23 ± 423 ± 425 ± 50.731
Waist circumference (cm)80 ± 787 ± 1183 ± 140.389
Western diet1 (8)5 (33)2 (40)0.0990.10.787
Japanese diet9 (69)6 (40)3 (60)0.1220.710.436
Meat diet4 (31)2 (13)2 (40)0.2620.710.197
Fish diet0 (0)2 (13)0 (0)0.1720.389
Vegetable diet2 (15)1 (7)0 (0)0.4570.3520.554
Well-balanced diet4 (31)6 (40)3 (60)0.6110.2550.436
History of laparotomy3 (23)0 (0)2 (40)0.0660.4730.016
Severity of abdominal pain5.4 ± 2.75.7 ± 2.65.4 ± 2.10.962
Stool form
BSFS6.4 ± 0.54.9 ± 1.25.4 ± 0.5< 0.001< 0.0010.0450.257
Proportion of BSFS 6+713 (100)6 (40)2 (40)0.0010.002> 0.999
DICA classification
Diverticular location1 ± 02 ± 02 ± 0
Number of diverticula0.9 ± 0.30.6 ± 0.51 ± 00.051
Inflammations000
Complications000
DICA total point1.9 ± 0.32.6 ± 0.53 ± 0< 0.001< 0.001< 0.0010.055
DICA 1: 1-3 points13 (100)15 (100)5 (100)
DICA 2: 4-7 points000
DICA 3: > 7 points000
Blood test
hsCRP (mg/dL)0.4 ± 0.20.5 ± 0.20.5 ± 0.20.245
hsCRP (> 0.3 mg/dL)8 (62)13 (87)4 (80)0.1260.4570.718
Fecal test
Calprotectin (μg/g)44 ± 2445 ± 2752 ± 450.865
Calprotectin (> 15 μg/g)11 (85)12 (80)3 (60)0.7510.2610.371
SF-36
PCS39 ± 1339 ± 333 ± 60.610
MCS49 ± 1140 ± 739 ± 70.0200.0100.0430.905
RCS33 ± 1328 ± 1330 ± 170.661
JPAC-QOL
Overall0.8 ± 0.40.9 ± 0.31.0 ± 0.10.457
Physical discomfort0.2 ± 0.20.2 ± 0.20.6 ± 0.30.0080.8600.0030.005
Psychosocial discomfort0.4 ± 0.30.4 ± 0.30.5 ± 0.20.843
Worries/concerns0.8 ± 0.50.8 ± 0.41.0 ± 0.30.763
Satisfaction1.9 ± 1.02.2 ± 0.62.3 ± 0.30.533
PAC-SYM
Overall1.0 ± 0.41.0 ± 0.41.1 ± 0.50.805
Stool symptom0.2 ± 0.20.3 ± 0.30.3 ± 0.20.735
Rectal symptom0.1 ± 0.20.3 ± 0.30.1 ± 0.20.080
Abdominal symptom2.1 ± 0.92.1 ± 0.82.4 ± 1.10.847

R, right; L, left; B bilateral; BMI, body mass index; BSFS, Bristol stool form scale; DICA, Diverticular Inflammation and Complication Assessment; hsCRP, high sensitivity C reactive protein; SF-36, 36-item short-form health survey; PCS, physical component summary; MCS, mental component summary; RCS, role/social component summary; JPAC-QOL, Japanese version of the patient assessment of constipation quality of life; PAC-SYM, Patient Assessment of Constipation-Symptoms.

Data are shown in mean ± SD, n (%), or n.



Symptomatic Uncomplicated Diverticular Disease Characteristics and Quality of Life According to Site

Table 4 presents a comparison of SUDD characteristics and QOL according to diverticular site. In total, 36% of SUDD cases were right-sided. Patients with left-sided SUDD were significantly more likely to be men than those with right-sided SUDD. Patients with SUDD on the left side were less likely to have had previous laparotomy than patients with SUDD on the right side or bilateral SUDD. No significant between-group differences in diet or body size were observed based on the location of the diverticula.

Among patients with SUDD, the locations of diverticulosis were not related to the intensity of abdominal pain. BSFS scores were significantly higher for right-sided SUDD than for left-sided SUDD, and more patients had a BSFS score of 6 or 7. The SF-36 MCS score was significantly higher in the SUDD group with diverticula on the right side only. The physical discomfort scores on the JPAC-QOL were significantly higher in the bilateral SUDD group than in the right-sided and left-sided SUDD groups. However, no significant differences in PAC-SYM scores according to the diverticular site were observed among patients with SUDD.

Post-diverticulitis Symptomatic Uncomplicated Diverticular Disease Characteristics and Quality of Life

Among 33 patients with SUDD, the proportion of post-diverticulitis symptomatic uncomplicated diverticular disease (PD-SUDD) patients was 30% (10 patients), none of whom had a history of complicated diverticulitis. We compared symptoms between PD-SUDD patients and other SUDD patients (non-PD-SUDD). There was no significant difference in the percentage of patients with abdominal bloating, constipation, diarrhea, or severity of abdominal pain (Supplementary Table 1) or in BSFS, DICA total point, blood levels of hsCRP, or fecal levels of calprotectin between the PD-SUDD and non-PD-SUDD groups. A history of diverticulitis was also found to have no effect on the QOL of SUDD patients (Supplementary Table 2).

Discussion

To the best of our knowledge, this study is the first epidemiological study to investigate right-sided SUDD and the effects of SUDD on QOL in an Asian population (Supplementary Fig. 3). In contrast to a previous European report that identified SUDD in 9% of patients with diverticulosis,1 SUDD was observed in 31% of our patients with diverticulosis with unexplained abdominal symptoms. This may be because the previous European study focused on patients who had undergone endoscopy, whereas our study population focused on patients who presented to an outpatient clinic with unexplained abdominal symptoms.

Our findings indicate that QOL was low in patients with SUDD visiting an outpatient clinic for unexplained abdominal symptoms compared with that in patients without SUDD. This suggests that patients with SUDD experience significant impairments in physical, mental, and role/social functioning. These findings are in accordance with those reported for patients with ulcerative colitis and Crohn’s disease.19 A European study examining QOL in patients with SUDD reported 12-item short-form health survey sub-scores of 46.1 for the PCS and 45 for the MCS.20 Again, these scores may have been lower among our patients than those in previous studies considering that the population consisted of outpatients with unexplained abdominal pain. Overall, these data highlight that SUDD can occur in Asian patients, likely resulting in poor QOL due to chronic, unexplained abdominal pain. In fact, SUDD was observed in 9% of the outpatients who reported unexplained abdominal pain in our study.

Patients with SUDD had more diarrhea symptoms and softer stools than those without SUDD. The causes of chronic diarrhea include inflammatory bowel disease, infection, IBS, alcohol, intestinal surgery, and increased bile acids in the stool.21 Patients with SUDD are known to overexpress tumor necrosis factor-alpha in the colonic mucosa compared with those who have asymptomatic diverticulosis and healthy individuals.22 SUDD has also been associated with nerve fiber growth and a relatively higher number of macrophages in close proximity to these fibers.23 In accordance with our findings, previous studies have reported that patients with SUDD have elevated levels of blood hsCRP24 and fecal calprotectin,25 which may be related to microinflammation. Herein, right- and left-sided SUDD were associated with high levels of hsCRP and fecal calprotectin; however, no significant difference between right- and left-sided SUDD was observed. Secondary bile acids have been reported to induce microinflammation of the intestinal tract.26 Diarrheal symptoms and abdominal pain may be related to bile acids in the stool.

This is the first epidemiological study of SUDD in outpatients with unexplained abdominal symptoms in Asia. Additional strengths of the study include analyses of right-sided SUDD, stool shape, and QOL, as well as the prospective sampling design. However, there are also some limitations, including the small number of cases, restriction of cohorts to the Japanese population only, inclusion of localized target patients only, and lack of correlation between histological inflammatory findings and SUDD prevalence. Future studies should also aim to conduct epidemiological analyses among endoscopically screened patients.

In outpatients with unexplained abdominal symptoms, the portion of patients with SUDD was 31% of the total number of patients with diverticulosis with abdominal symptoms, of whom 39% having right-sided SUDD. Patients with SUDD have a low QOL; thus, it is important to recognize the presence of SUDD. Furthermore, SUDD is associated with diarrhea symptoms and mild inflammation of the intestinal tract, and further pathophysiological studies are needed.

Supplementary Materials

Note: To access the supplementary figures and tables mentioned in this article, visit the online version of Journal of Neurogastroenterology and Motility at http://www.jnmjournal.org/, and at https://doi.org/10.5056/jnm22162.

Financial support

None.

Conflicts of interest

Atsushi Nakajima reports grants and research support from Gilead, Mylan EPD, EA Pharma, Kowa, Taisho, and Biofermin and is a consulting adviser for Gilead, Boehringer Ingelheim, BMS, Kowa, Astellas, EA Pharma, and Mylan EPD. The other authors declare no conflicts of interest.

Author contributions

Conceptualization and project administration: Takaomi Kessoku and Atsushi Nakajima; methodology: Tsumugi Jono, Yuki Kasai, Takaomi Kessoku, and Atsushi Nakajima; investigation: Atsushi Nakajima, Tomoki Ogata, Kosuke Tanaka, Tsutomu Yoshihara, Noboru Misawa, Shingo Kato, Takuma Higurashi, Kunihiro Hosono, Masato Yoneda, Kosuke Seita, Takayuki Kato, Eiji Sakai, Takeo Kurihashi, and Machiko Nakatogawa; funding acquisition: Atsushi Nakajima; formal Analysis: Shunsuke Oyamada; writing of original draft: Tsumugi Jono, Yuki Kasai, and Takaomi Kessoku; Writing of review and editing: Tsumugi Jono, Yuki Kasai, Takaomi Kessoku, Atsushi Nakajima, Tomoki Ogata, Kosuke Tanaka, Tsutomu Yoshihara, Noboru Misawa, Shingo Kato, Takuma Higurashi, Kunihiro Hosono, Masato Yoneda, Kosuke Seita, Takayuki Kato, Eiji Sakai, Takeo Kurihashi, Machiko Nakatogawa, Shunsuke Oyamada, Seiji Futagami, Kok-Ann Gwee, and Atsushi Nakajima.

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