IBS病患不會比較容易發生大腸癌

作者：Pauline Anderson  
出處：WebMD醫學新聞

　　April 7, 2010 — 根據一篇新研究，大腸的一般結構性異常，例如息肉、痔瘡、大腸直腸癌(CRC)、憩室炎等的發生率，在無便秘的大腸激躁症(irritable bowel syndrome，IBS)患者並沒有比接受大腸鏡篩檢CRC的健康對照組高。
　　
　　這些研究發現支持美國胃腸道學院最近的建議，對於典型IBS症狀的病患，沒有無法解釋的體重減輕、無發燒、無明顯胃腸道出血者，不進行例行性大腸影像檢查。
　　
　　【長久以來的偏見】
　　Brennan M.R. Spiegel醫師向Medscape Gastroenterology表示，長久以來有個偏見：不知何故，腹瀉、便秘、脹氣等等腹部問題的病患，會有較高的惡性腫瘤風險。
　　
　　不過，他指出，只有大約1%的大腸鏡檢查是在可能有實質發現如結腸炎的IBS病患進行。
　　
　　Spiegel醫師是加州大學洛杉磯分校、David Geffen醫學院、VA Greater Los Angeles健康照護體系、內科助理教授、加州大學洛杉磯分校/ VA結果研究與教育中心主任。
　　
　　密西根大學健康體系胃腸科William D. Chey醫師領導的此項研究，線上發表於2月23日的美國胃腸病學期刊(American Journal of Gastroentrology)。
　　
　　這個前瞻觀察型、案例控制多中心試驗，比較了466名無便秘之IBS病患進行大腸鏡檢查，以及451名健康志願者根據個人之腺瘤性息肉史、以大腸鏡檢查進行例行CRC篩檢時的結構性病灶盛行率。
　　
　　【年輕人與婦女】
　　相較於控制組，疑似有IBS這組的病患明顯比較年輕、且較多女性。兩組的種族組成上不無二致，每個世代的白人比率(80-85%)和黑人比率(大約10%)相當。
　　
　　在疑似IBS病患的大腸鏡檢查中，研究者辨識並紀錄所有的異常，他們進行息肉和/或異常黏膜之切片，且從乙狀結腸和直腸取樣至少兩個隨機切片。
　　
　　控制組進行大腸鏡檢查時發現的異常也進行紀錄，但是只有發現肉眼可見之異常時才進行切片。
　　
　　【最常見的病灶】
　　研究者發現，疑似IBS病患組最常見的大腸病灶依序是痔瘡(18.2%)、息肉(14.6%)、憩室(8.8%)以及紅斑或潰瘍(4.9%)。控制組中，最常見的發現依序是息肉(34.4%)、憩室(21.3%)以及痔瘡(16.4%)。控制組的息肉和憩室炎比率顯然高於疑似IBS病患組(分別是34.4% vs 14.6%以及21.3% vs 8.8%；兩者的差異顯著程度皆為P < .0001)。
　　
　　疑似IBS病患組的肉眼可見紅斑或潰瘍的比率顯著高於控制組(4.9% vs 1.8%；P < .01)。
　　
　　IBS組最常見的組織學發現是增生性息肉(8.4%)以及腺瘤(7.7%)，而比較年長的控制組則剛好相反，腺瘤最常見(26.1%)，接著是增生性息肉(11.5%)。
　　
　　校正年紀、性別、種族、教育程度、抽菸、飲酒等之後，疑似IBS病患組的腺瘤發生率為0.33(95%信心區間[CI]為0.20 - 0.56)，相較於控制組，IBS組的憩室炎和痔瘡校正勝算比分別是0.68 (95% CI，0.42 - 1.1)和1.2 (95% CI，0.75 - 1.8)。
　　
　　作者們解釋，控制組的腺瘤盛行率較高可能是因為，該組因有大腸息肉或癌症家族史而進行大腸鏡檢查的病患數較少，且本研究未納入一等親有大腸癌的IBS病患。
　　
　　【微小性結腸炎】
　　微小性結腸炎(Microscopic colitis)可能被誤認為是IBS，在疑似IBS病患中僅佔約1.5%，其中多數是女性，且這些女性年紀都在35歲以上，此一比率在45歲以上的IBS病患增加到2.3%。作者們寫道，可能是我們的研究低估了IBS病患微小性結腸炎的實際盛行率，而僅要求內視鏡醫師從乙狀結腸和直腸取兩個切片，用來診斷微小性結腸炎之大腸黏膜切片的適當數量與位置依舊有所爭議。
　　
　　作者們寫道，醫師們擔心沒有發現疑似IBS病患的大腸直腸癌或發炎性腸道疾病，通常會使用大腸鏡來評估IBS症狀，最近的全國資料庫分析發現，美國約有四分之一的大腸鏡檢查是用於IBS相關症狀。
　　
　　Spiegel醫師將此數據稱之為「荒謬絕倫」，特別是這個技術未普及且昂貴。有一堆人在等這有限的資源，如果我們開始推動可能影響達10%人口的IBS患者接受檢查，將很難獲得適當的篩檢。
　　
　　【可能的限制】
　　作者們表示，人口統計學和大腸鏡檢查適應症上的差異可能會影響研究結果，另外的研究限制是，該研究未蒐集併發症比率，而這可能會影響風險-利益分析，研究結果無法擴展到其他類型的IBS患者。
　　
　　根據美國胃腸道學院的建議，除了用來篩檢50 歲以上者的大腸直腸癌之外，只可對有警訊的IBS病患進行大腸鏡檢查，以排除器質性疾病。該學院建議，當對IBS病患進行大腸鏡檢查時，醫師應考慮採隨機切片排除微小性結腸炎。
　　
　　Spiegel醫師表示，若有IBS，時間站在我們這邊，所以，如果有人病程不同於一般情況或者對一般治療沒有反應、或者症狀有點異於常規，我們一定要保留執行大腸鏡檢查；只是我們一定要記住，即使是這個情況，獲益依舊相當低。
　　
　　Spiegel醫師表示，大腸鏡檢查的另一個合理使用是用來再度確認IBS病患症狀未惡化，我可以告訴他們，除非我面有難色，否則他們就沒有罹患癌症、沒有大腸炎、裡面也沒有蟲，但是有些人非得要醫師進行體內檢查才會相信；他們需要的是某些確認。
　　
　　他表示，不過，大腸鏡檢查的陰性結果似乎無法提供預期的再度確認，一篇已經發表的研究發現，這類陰性結果並未改善IBS病患的生活品質，他們傾向於繼續相信有某件事情嚴重出錯。
　　
　　Chey醫師是Albireo、Aryx、AstraZeneca、Ironwood、McNeil、Proctor Gamble、Prometheus、Salix、Smart Pill Corporation、Takeda與Xenosport等的顧問，也擔任Axcan、Prometheus、Salix與Takeda等的發言人。至於其他作者的利益衝突資料，請參考原始文獻。Spiegel醫師接受Takeda Pharmaceuticals、Prometheus Laboratories與Rose Pharmaceuticals等提供的資金支持。他也擔任Prometheus 與Ironwood Pharmaceuticals的顧問。
　　
　　Am J Gastroenterol. 線上發表於2010年2月23日。


Patients With IBS Not More Likely to Develop Polyps or Colon Cancer

By Pauline Anderson
Medscape Medical News

April 7, 2010 — The prevalence of common structural abnormalities of the colon, including polyps, hemorrhoids, colorectal cancer (CRC), and diverticulosis, is no higher in nonconstipated patients with irritable bowel syndrome (IBS) than in healthy control patients undergoing colonoscopy for CRC screening, according to a new study.

The findings lend support to the recent recommendation of the American College of Gastroenterology not to use routine colonic imaging in patients with typical IBS symptoms who have no alarm features such as unexplained weight loss, fever, or significant gastrointestinal bleeding.

Long-Standing Bias

"There has been a bias for a long time that patients with chronic abdominal complaints — diarrhea, constipation, bloating, and so forth — may somehow be at higher risk of harboring underlying malignancy," commented Brennan M.R. Spiegel, MD, to Medscape Gastroenterology.

However, he added, only about 1% of colonoscopies performed on patients with IBS will find something substantial; for example, colitis.

Dr. Spiegel is assistant professor of medicine, VA Greater Los Angeles Healthcare System, David Geffen School of Medicine at the University of California–Los Angeles, and director, University of California–Los Angeles/VA Center for Outcomes Research and Education.

The study, led by William D. Chey, MD, from the Division of Gastroenterology, University of Michigan Health System, Ann Arbor, was published online February 23 in the American Journal of Gastroentrology.

The prospective, observational, case-controlled, multicenter trial compared the prevalence of structural lesions of the colon found during colonoscopy in 466 patients with nonconstipated IBS with that of 451 healthy volunteers undergoing colonoscopy for routine CRC screening based on a personal history of adenomatous polyps.

Younger, Women

Patients in the group with suspected IBS were significantly younger and more likely to be women compared with those in the control group. There was no disparity in racial makeup of the 2 groups with equivalent numbers of white (80-85%) and black (roughly 10%) patients in each cohort.

During colonoscopies in patients with suspected IBS, investigators identified and recorded all abnormalities. They biopsied polyps and/or mucosal abnormalities and obtained at least 2 random biopsies from the sigmoid colon and rectum.

Abnormalities identified during colonoscopy in the control group were similarly recorded, but colon biopsies were only performed in this group when a visible abnormality was identified.

Most Common Lesions

The researchers found that the most common colonic lesions in patients with suspected IBS were hemorrhoids (18.2%), followed by polyps (14.6%), diverticuli (8.8%), and erythema or ulceration (4.9%). In the control group, the most common findings were polyps (34.4%), followed by diverticuli (21.3%) and hemorrhoids (16.4%). The control group had a significantly higher prevalence of polyps and diverticulosis compared with those patients with suspected IBS (34.4% vs 14.6% and 21.3% vs 8.8% respectively; both differences significant to the P < .0001 level).

The prevalence of macroscopically visible mucosal erythema or ulceration was significantly higher in patients with suspected IBS compared with control patients (4.9% vs 1.8%; P < .01).

The most common histologic findings in the IBS group were hyperplastic polyps (8.4%) and adenomas (7.7%), whereas in the control group the order was reversed -- adenomas were the most common (26.1%) followed by hyperplastic polyps (11.5%).

After adjusting for age, sex, race, level of education, smoking, and alcohol use, the odds ratio for the presence of adenomas in patients with suspected IBS compared with control patients was 0.33 (95% confidence interval [CI], 0.20 - 0.56). The adjusted odds ratios for the presence of diverticulosis and hemorrhoids in the IBS group compared with the control patients were 0.68 (95% CI, 0.42 - 1.1) and 1.2 (95% CI, 0.75 - 1.8), respectively.

The prevalence of adenomas was higher in the control group possibly because a substantial minority of control patients undergoing colonoscopy had a family history of colon polyps or cancer, whereas patients with IBS with a first-degree relative with colon cancer were not eligible for inclusion in the study, explained the authors.

Microscopic Colitis

Microscopic colitis, which can be mistaken for IBS, was identified in only about 1.5% of patients with suspected IBS, most of whom were women, and all of whom were older than 35 years. The prevalence increased to 2.3% in patients with IBS older than 45 years. "It is possible that our study underestimated the true prevalence of microscopic colitis in IBS patients as the protocol required the endoscopist to obtain only two biopsies from the sigmoid and rectum," wrote the authors. "The optimal number and location of colonic mucosal biopsies needed to diagnosis microscopic colitis remains controversial."

Physicians are concerned about missing colorectal cancer or inflammatory bowel disease in patients with suspected IBS and often use colonoscopy to evaluate IBS symptoms, wrote the authors. A recent national database analysis found that roughly one quarter of all colonoscopies performed in the United States are for IBS-related symptoms.

Dr. Spiegel called this figure "outrageous," especially when the technology is scarce and expensive. "We've got queues forming of individuals waiting for fixed resources, and if we start pushing other individuals who have IBS — something that affects up to 10% of the population — into those queues, then it's going to be very difficult to get proper screening."

Possible Limitations

Differences in demographics and indications for colonoscopy may have influenced the study results, said the authors. Another limitation is that the study did not collect information on complications rates, which would have contributed to a risk–benefit analysis. The results do not necessarily extend to other subgroups of patients with IBS.

According to the American College of Gastroenterology recommendations, in addition to being used to screen for colorectal cancer in those older than 50 years, colonoscopic imaging should be performed in patients with IBS only with alarm features, to rule out organic diseases. The college recommends that when performing colonoscopy in patients with IBS, physicians should consider obtaining random biopsies to rule out microscopic colitis.

"With IBS, time is on your side, so if someone's not following the script and isn't responding to the usual treatments, or the symptoms are a little bit off the beaten path, we should always reserve the right to do a colonoscopy; but we should still keep in mind that even in that situation, the yield remains very low," said Dr. Spiegel.

One of the rationales for using colonsocopy is to reassure IBS patients that there is nothing seriously wrong, said Dr. Spiegel. "I can tell them until I'm blue in the face that they do not have cancer, don't have colitis, and there's no worm inside, but some people, until we actually physically look in there, won't believe it; they need some confirmation."

However, negative results from a colonoscopy does not seem to offer the expected reassurance, he said. One published study found that such a negative result did not improve the quality of life for patients with IBS, and they tended to continue to believe that there was something seriously wrong.

Dr. Chey is a consultant for Albireo, Aryx, AstraZeneca, Ironwood, McNeil, Proctor & Gamble, Prometheus, Salix, Smart Pill Corporation, Takeda, and Xenosport and has been a speaker's bureau member for Axcan, Prometheus, Salix, and Takeda. For conflict of interest information on other authors, please refer to the original article. Dr. Spiegel receives grant support from Takeda Pharmaceuticals, Prometheus Laboratories, and Rose Pharmaceuticals. He is also an adviser for Prometheus and Ironwood Pharmaceuticals.

Am J Gastroenterol. Published online February 23, 2010.