論文英文簡述

Background:

Irritable bowel syndrome (IBS) is a common functional GI disorder. The clinical presentation and pathophysiologic mechanisms of IBS has overlap with some organic GI disease. Recent researches showed the presence of colonic diverticulosis (CD), especially left-sided diverticulosis, was associated with higher risk of IBS.

However, conflicting findings were observed in the studies conducted in Asian population. Larger prospective studies are needed to confirm the association. Low grade inflammation and alteration in gut microbiota play important role in the pathophysiologic mechanism of symptomatic diverticular disease (DD). Recent studies have focused on the use of 5-ASA, antibiotics and probiotics in treating chronic diverticular disease. It is of clinical importance to distinguish IBS and chronic symptomatic diverticular disease to define the appropriate treatment. The effectiveness of abdominal pain lasting for more than 24 hours could discriminate IBS and DD had been proposed. Further validation is needed.

Objectives:

We conducted prospective study to 1. clarify the association between IBS and CD in Taiwanese population; 2. Validate the effectiveness of abdominal pain lasting for more than 24 hours in differentiating IBS and DD.

Methods:

We enrolled patients undergoing colonoscopy in single hospital. Questionnaire was applied to identify IBS patients (according to Rome III criteria) and to collect the characteristics of abdominal pain. We compared 1. the prevalence of CD in the IBS and non-IBS groups. 2. The prevalence of the clinical symptom of abdominal pain lasting for more than 24 hours in pure (no overlap) IBS and pure DD groups.

Results:

We initially enrolled 1502 subjects during March 2016 to November 2016 and 119 subjects met the exclusion criteria. A final total of 1383 subjects were enrolled for

was 1.58:1. IBS was identified in 6.6% and CD was observed in 17.1% of the patients. Right-sided diverticulosis is predominant (69% of all CD). There was no statistically significant difference between the prevalence of whole CD (14.3% vs 17.3%, P=0.455), right-sided CD(8.8% vs 12.0%, P=0.359) and left-sided CD(2.2%

vs 2.6%, P=0.435) in IBS and non-IBS groups. Significantly higher BSRS-5 score was observed in the IBS group. In younger (age<65) IBS patients, the prevalence of colonic adenoma was lower (OR:0.43, P=0.012). There was no significant difference between the prevalence of IBS in CD and non-CD groups (5.5% vs 6.8%, P=0.455).

Older age was the most important risk factor for CD (OR:2.04,P=0.000). Alcohol consumption (OR:1.48,P=0.037) and higher BMI (OR:1.09, P=0.000) also increased the risk of CD. Within the whole diverticulosis group, abdominal pain was

complained in 28.3% of the patients. Higher BSRS-5 score was observed in this subgroup (symptomatic diverticular disease). The pain duration, severity and location could not differentiate pure IBS and pure symptomatic DD in our study.

Discussion:

In our Taiwanese population, the prevalence of IBS was 6.6%, predominantly mixed and diarrhea subtypes, accounting for 44.0% and 39.6% respectively. The prevalence of colonic diverticulosis (CD) was 17.1%, predominantly right-sided diverticulosis, accounting for 69% of all colonic diverticulosis. This finding is consistent with past studies in Asian population. However, we do not see any association between CD (either left or right) and IBS. Possible reasons are as follows:

1. The mean age of our study population is lower: In Yamada E’s study, the mean age was 64.2 years and the prevalence of CD was as high as 40.2% (Yamada E et al.

2014). The mean age of our study population was only 55.8 years. The age difference may partially explained the lower prevalence of CD in our study (17.1%). Despite the attempt of age-stratified analysis, we were not able to see associations between IBS and CD in younger (age <65) or older (age ≥ 65) subgroups.

2. The studies were hospital-based. Studied population was screened by certain probably different criteria: The prevalence of IBS was 7.5% in Yamada E's study, and all patients received colonoscopy for colorectal cancer screening. The

mentioned in their study (Yamada E et al. 2014). The prevalence of IBS in our study was 6.6%. About 27.9% of patients received colonoscpy for positive iFOBT. A total of 42.3% of patients had abdominal pain, changes in bowel habits, bloody stool or other GI symptoms. The two studied populations were screened by different criteria and this may partly explained the differenct results.

3. The prevalence of CD in our study may be underestimated: In addition to age factor, the lower diverticulum detection ability of colonocscopy may also contribute to the low CD prevalence in our study. The detection ability of

colonoscopy for small lesions or diverticula largely depended on the adequacy of bowel cleaning. For high-quality colonoscopy, the cecal intubation rate should be more than 95%, the adequacy of bowel cleaning (excellent or good by Aronchick scale) should be 85-90% or more, and the adenoma detection rate (ADR) should be 20% -25% or more. In our study, the ADR was quite good (38.4%) but the adequacy of bowel cleaning was suboptimal (72.5%). This may hinder the detection of diverticulum. Yamada E did not mentioned the quality index of their colonoscopy. They used a transparent hood attached to the tip of the colonoscope during examination. Previous studies had shown the use of a transparent hood can fascilitate small lesions detection (Kondo S et al. 2007). Furthermore, it has been proposed that colonoscopy may have a lower rate of detection of colonicl

diverticula than barium enema (Niikura R et al. 2013). In Taiwan, due to the easy accessibility and therapeutic potential, colonoscopy has replaced most of the role of barium enema. If we use barium enema as the final confirmative study for colonic diverticulosis, we may require a much longer time for case enrollment or a multi-center study design.

Comparison of IBS and non-IBS groups:

Past studies have found that psychosocial stress are associated with the development of IBS (Drossman DA et al. 1988). In our study, significantly higher BSRS-5 score was found in the IBS group, regardless of age strata. In our study, the younger (age <65) IBS subgroup had a lower adenoma prevalence. This finding had been mentioned in Gu HX’s study of the young Chinese population (Gu HX et al. 2011), but the causal relationship is still unknown.

Comparison of CD and non-CD groups:

In our study, age was the most important risk factor for colonic diverticulosis, with an odds ratio of 2.04 (P = 0.000) for age more than 65 years. Previous studies in Hjern F and Strate LL shown that obesity and physical inactivity increased the risk of diverticulitis and diverticular bleeding (Hjern F et al. 2012; Strate LL et al. 2009). Our study also found that BMI was significantly higher in the younger (age < 65) CD subgroup. This may be associated with abnormal colon motility. Alcohol use was found to be a risk factor for colonic diverticulosis. The finding was consistent with several previous studies (Song JH et al. 2010; Nagata N et al. 2013; Sharara AI at al. 2013). The reason is still unclear, but rat studies have shown that alcohol consumption may activate NF-κB, up-regulate iNOS, increase NO release in myenteric plexus and finally inhibit colon motility (Wang et al. 2010).

Comparison of asymptomatic colonic diverticulosis and symptomatic diverticular disease:

Within the whole colonic diverticulosis group (n=237), 28.3% (n=67) of the patients were symptomatic. They suffered from abdominal pain and the chronicity (>

6months) was noted in 9.7% (n=23) of the patients. After multivariate analysis, significantly higher BSRS-5 score was observed in this subgroup (symptomatic diverticular disease). While treating these patients, increased psychosocial stress due to chronic pain should be concerned.

Comparison of the characteristics of abdominal pain between pure IBS and pure symptomatic diverticular disease (DD):

In Cuomo R and Tursi A’s studies pointed out the clinical symptom of severe and persistent (more than 24 hours) abdominal pain can differentiate symptomatic diverticular disease and IBS (Cuomo R et al. 2013; Tursi A et al. 2015). This finding could not be validated in our study. Western and Asian ethnic difference of the colonic diverticulosis may contribute to the result. Right-sided diverticulosis are predominant in Asian population. Of the 54 patients with pure symptomatic

diverticular disease, 39 patients has the right-sided diverticulosis. Although we tried to analyze right and left/bilateral diverticular disease separately, we could not see

The limitations of our study are as follows: This study is a hospital-based study, the generalizability of the results should be concerned. The suboptimal bowel cleansing and probably lower colonoscopic detection ability for left side diverticulum may have influence on the results. The diagnosis of IBS is by

questionnaires. The enrolled subjects have to recall their characteristics of abdominal pain and bowel habit in the past 3 to 6 months. Recall bias is inevitable. Furthermore, the case numbers of IBS and left-sided diverticulosis were still too small. Due to the low prevalence of IBS and left-sided diverticulosis (IBS: 6.6%, LD: 2.5%) in the Taiwanese population, a multi-center study design and longer time for case enrollment may be needed.

Conclusions:

In Taiwaness population, right-sided diverticulosis is predominant. The association between colonic diveticulosis and IBS was not observed in our study. The

effectiveness of abdominal pain lasting for more than 24 hours in differentiating IBS and DD also could not be validated. IBS patients had higher psychosocial stress.

Younger IBS patients had lower adenoma prevalence. Older age is the most

important risk factor of CD. Alcohol consumption and obesity increased the risk of CD. Patients with symptomatic diverticular disease had higher psychosocial stress.

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 圖表:

圖 1 大腸憩室症之分類及學術名詞定義

(13. Am J Gastroenterol. 2012 Oct;107(10):1486-93.)

圖 2 大腸憩室疾病可能之病生理機轉及其相關治療 (13. Am J Gastroenterol. 2012 Oct;107(10):1486-93.)

(Symptomatic uncomplicated diverticular disease)

(Segmental colitis associated with diverticulitis)

圖 3 收案流程圖

腸胃道症狀及心理健康問卷

(版本/日期: Version 1.0/2015-12-25)

1. 請問您的性別為男女，年齡_________

身高: ________ 公分體重: ________ 公斤 2.請問您是否有抽菸? 有 ____ 包/天 ____ 年

無 3.請問您是否有飲酒習慣有無

4.請問您在過去三個月是否有使用下列藥物:

軟便藥/瀉藥有無消炎止痛藥有無

類固醇有無降血壓藥有無

降膽固醇藥物有無

5.請問過去是否曾接受過腹部或骨盆腔手術有，何手術?______________

無

請您仔細回想，在最近三個月中，下面五個問題使您感到困擾或苦惱的程度:

06. 睡眠困難，譬如難以入睡、易醒來或早醒來

完全沒有輕微中等程度厲害非常厲害 07. 感覺緊張不安

完全沒有輕微中等程度厲害非常厲害 08. 覺得容易苦惱或動怒

完全沒有輕微中等程度厲害非常厲害 09. 感覺憂鬱、心情低落

完全沒有輕微中等程度厲害非常厲害 10. 覺得比不上別人

完全沒有輕微中等程度厲害非常厲害

11.請問您接受大腸鏡檢查的原因為何?

20.當腹部不舒服或腹痛發生時，解大便的頻率、次數是否有比平常增加?

24.在過去的三個月，解出的大便是否堅硬成塊?

大便從未堅硬成塊

大便有時候堅硬成塊 (25%以上的時候) 大便常常堅硬成塊 (50%以上的時候) 大便大部分堅硬成塊 (75%以上的時候) 大便總是堅硬成塊

25.在過去的三個月，解出的大便是否鬆散不成條?

大便從未鬆散不成條

大便有時候鬆散不成條 (25%以上的時候) 大便常常鬆散不成條 (50%以上的時候) 大便大部分鬆散不成條 (75%以上的時候) 大便總是鬆散不成條

---

大腸鏡檢查日期:

檢查是否到達盲腸: 是 / 否是否發現息肉: 是 / 否

清腸程度: Excellent / Good / Fair / Poor

是否發現大腸憩室: 是 / 否

大腸憩室位置: 右側 / 左側 / 雙側

大腸憩室數量: 小於 5 / 大於等於 5

圖 4 收案流程圖---最終收案結果

表 1 病人特色

Operation history 20.8

Good bowel cleansing (%) 72.5

Adenoma, ADR (%) 38.4

Diverticulosis (%,n) 17.1 (237)

RD (%,n)

BMI:body mass index; BSRS-5:Brief Symptom Rating Scale-5; Good bowel cleansing:good and excellent by Aronchick scale; ADR:adenoma detection rate; RD:right diverticulosis; LD:left diverticulosis; BD:bilateral diverticulosis；C-IBS:constipation type IBS; D-IBS:diarrhea type IBS;

M-IBS:mixed type IBS; U-IBS:un-subtype IBS

表 2 有大腸激躁症及無大腸激躁症群組之比較 BMI:body mass index; BSRS-5:Brief Symptom Rating Scale-5; Good bowel cleansing:good and excellent by Aronchick scale; ADR:adenoma detection rate;

RD:right diverticulosis; LD:left diverticulosis; BD:bilateral diverticulosis c Chi-square test

t Student’s t test

* P < 0.05

表 3-1 大腸激躁症危險因子之多變數回歸分析

Table 3-1. Results of the multiple logistic regression analysis for independent risk of IBS

Odd ratio 95% CI P value

Age 0.99 0.97-1.00 0.131

Laxatives use 2.35 1.47-3.75 0.000*

Analgesics use 1.23 0.78-1.95 0.368

BSRS-5 1.17 1.11-1.23 0.000*

Operation history 1.47 0.92-2.36 0.108

Adenoma, ADR 0.68 0.40-1.14 0.145

Diverticulosis 1.44 0.42-4.99 0.565

RD 0.52 0.12-2.15 0.365

LD 0.76 0.11-5.10 0.781

BSRS-5:Brief Symptom Rating Scale-5; ADR:adenoma detection rate; RD:right diverticulosis; LD:left diverticulosis