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Emerging Studies in Diverticular Disease

Floch, Martin H. MD

Journal of Clinical Gastroenterology: May/June 2013 - Volume 47 - Issue 5 - p 381–382
doi: 10.1097/MCG.0b013e318282918d
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Section of Digestive Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT

M.H.F. was an investigator in the recent Prevent Shire Study and has been a speaker for Proctor & Gamble.

Reprints: Martin H. Floch, MD, Section of Digestive Diseases, Department of Internal Medicine, Yale University School of Medicine, P.O. Box 208019, LMP 1080, New Haven, CT 06520 (e-mail: martin.floch@yale.edu).

With encouragement from a patient who had suffered from complications arising from diverticulitis, we formed the National Diverticulitis Study Group in 2002.1 This group went on to hold several national workshop meetings and stimulate work in the field of diverticulitis and, with the support of gastroenterologists in Europe, published several reviews. It helped stimulate several large research studies, such as the DIVA Study and those supported by Shire.2,3

Diverticular disease and diverticulitis appear to be chronic illnesses that were first described in the early 19th century, and, during its rapid increase in incidence in the 20th century, as noted by British and South African epidemiologists, basic observations were recorded.4 Diverticular disease has become one of the most common gastrointestinal disorders. The estimated prevalence rate ranges from 60% to 70% in humans older than 60 years of age. Most patients have asymptomatic diverticular disease, but as many as 20% will have symptoms. Symptoms may range from so-called symptomatic, uncomplicated diverticular disease to abscess formation and perforation with fistula.5,6

It is now accepted and assumed that colonic pseudodiverticulum occurs as a fiber-deficiency disease.7,8 The hallmark work of Painter and Burkitt, followed by years of analyses, has established this fact. A recent, extensive review of patients revealed that fiber deficiency indeed correlated with diverticular formation, but surprisingly there was little correlation of nut, corn, and popcorn consumption with the incidence of acute diverticulitis.9 Although the fiber-deficiency theory has been challenged by many, in particular, by the study by Peery et al,10 the continuous review of the data in studies such as the one by Dr Strate’s9 and an extensive review in England by Dr Crowe and colleagues continue to confirm the epidemiologic theory that fiber deficiency is the main cause of pseudodiverticular formation in the colon.11

Because there continues to be interest in the widespread occurrence of diverticular disease, there are 3 papers on this issue that discuss different aspects12–14: the continued study of the epidemiology12; the association with prevalent comorbidities, such as Clostridium difficile infection (CDI)13; and other nutritional factors such as alcohol.14

In a study from Israel, Lahat et al12 identified 261 patients between 2000 and 2006 who had perforations because of acute diverticulitis and who were followed up after discharge. The follow-up time was 88±22 months. Younger patients were seen to have experienced more complications during hospitalization (37% vs. 12.5%) and underwent more sigmoidectomy operations during their follow-up period. They found that older patients tended to be less symptomatic after discharge. Todd ratio for sigmoidectomy after complicated acute diverticulitis was 16.2%, and age did not affect the risk for surgery.12 Beddy and Wolff15 carefully reviewed the literature on recurrent diverticulitis and its complications in the younger age group and concluded that there may be a slight increase in incidence in individuals below the age of 50, but it is not significant and the data to date are still not clear as to whether there is increased recurrence at a younger age group and whether the disease is more severe in younger patients.15 From the present literature and from the study by Lahat and colleagues, we cannot draw any further conclusions. This is an important study as it brings us up-to-date with the present evaluation of the epidemiology of diverticulitis and brings forth the problem of age in the disease.

As diverticulitis of the colon is very common, it is of concern as to whether patients with diverticular disease have a different response to acute disease. C. difficile diarrhea continues to be a significant problem, and the paper by Feuerstadt and colleagues in which 265 patients were studied focuses on this issue.14 A total of 128 patients had C. difficile diarrhea, and 137 had no diarrhea. All patients underwent colonoscopy and C. difficile toxin assays. Primary outcomes included relapses within 3 months of initial infection of C. difficile and recurrent infection, which was a repeat CDI ≥3 months after the initial episode. Diverticular disease of the colon did not appear to be definitely associated with the risk for repeat CDI. However, a subgroup analysis revealed that patients with ascending colon diverticulosis did have an increased risk, but the numbers were small (only 48), and therefore the authors concluded that ascending diverticular disease as a risk factor could not be firmly confirmed on the basis of these data. The final conclusion was that diverticular disease is not a risk factor for relapse or recurrent CDI. This information is helpful clinically. Although perforation of the diverticulum is associated with increased mortality, the mere presence of diverticular disease does not appear to increase morbidity from CDI.15

Although it is well established that diverticular disease is related to fiber deficiency,4–9,11 there is always some uncertainty as it is very common, and thus nutritional factors are always being evaluated. In this issue, there is an excellent epidemiologic study on the use of alcohol consumption as a possible risk factor for colonic diverticulosis.16 Sharara and colleagues conducted a cross-sectional study on asymptomatic subjects undergoing screening colonoscopy and obtained detailed dietary and social information. A total of 746 individuals were enrolled. The prevalence of diverticulosis was 32.8%. In a univariate analysis, age, gender, presence of adenomatous polyps, advanced neoplasia, and aspirin and alcohol consumption were significantly associated with diverticulosis. When a multivariate analysis was performed, only increasing age, advanced neoplasia, and alcohol consumption were found to be significantly associated with diverticulosis. Other dietary factors, body mass index, physical activity, and bowel habits were not associated with diverticular disease. Odds ratio for diverticulosis in alcohol users was 1.91 (1.36 to 2.69) with increasing prevalence with higher alcohol consumption (a t value or trend of 0.001). The authors also looked at prevalence of diverticulosis in 18 countries, and when they analyzed alcohol use there was a strong correlation with the national per capita alcohol consumption rates. The authors felt that alcohol use is a significant risk factor for colonic diverticulosis and may offer a partial explanation for the existing east-to-west paradox in disease prevalence and phenotype. This study has several shortcomings; yet it is important because it points out a dietary association that has been poorly studied. In the epidemiologic study conducted by Strate et al,9 no association was found with increased alcohol intake. However, the statistical analysis performed in this study appears satisfactory. The authors point out that in a Danish study there was a relative risk of 2 for alcoholics to have admissions due to diverticular disease. The major shortcoming of this study is that alcohol intake was not graded. Hence, the authors cannot state whether small and large amounts had different effects. There is limited information on the type and duration of alcohol use. Although the study was conducted in Lebanon, the authors did analyze data from western nations that appeared to indicate that alcohol may have an association. This finding is interesting and warrants further work. The question as to how alcohol would increase diverticular information arises. Here, the authors suggest that it is based on a change in motility. There is no question that alcohol intake does affect gastrointestinal motility and, hence, could be related to some of the newer theories.

These 3 papers show that the interest in diverticular disease continues, leading to new treats in treatments. Both patients and health care providers find it necessary to treat symptomatic diverticular disease, and hence, the new evaluations on the use of anti-inflammatory agents and nonabsorbable antibiotics have come forth and are being evaluated at this time.17 The extensive DIVA and Shire Studies are further evaluating the use of 5-ASA, and the literature is now proposing the use of nonabsorbable antibiotics. Certainly, there will be continued interest in the treatment against symptomatic diverticular disease as it is widely prevalent.17,18

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REFERENCES

1. Floch MH. Colonic diverticulosis and diverticulitis: national diverticulitis study group, 2008 update. J Clin Gastroenterol. 2008;42:1123–1124
2. Stollman N, Magowan S, Shanahan F, et al. Efficacy of delayed-release mesalamine in the prevention of GI symptoms following acute diverticulitis: results of the DIVA trial. Am J Gastroenterol. 2010;105:S139
3. Shire Protocol SPD476.313. A phase III randomized, double-blind, dose-responsive, stratified, placebo-controlled study evaluating the safety and efficacy of SPD476 versus placebo over 104 weeks in the prevention of recurrence of diverticulitis. (Prevent Study)
4. Feagans J, Raskin JB. Historical perspectives and the spectrum of diverticular disease. J Clin Gastroenterol. 2011;45:S3–S6
5. Hemming J, Floch M. Features and management of colonic diverticular disease. Curr Gastroenterol Rep. 2010;12:399–407
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7. Painter NS, Burkitt DP. Diverticular disease of the colon: a deficiency disease of western civilization. Br Med J. 1971;2:450–454
8. Ravikoff JE, Korzenik JR. The role of fiber in diverticular disease. J Clin Gastroenterol. 2011;45:S7–S11
9. Strate LL, Lin YL, Syngal S, et al. Nut, corn and popcorn consumption and the incidence of diverticular disease. JAMA. 2008;300:907–914
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11. Crowe FL, Appleby PN, Allen NE, et al. Diet and risk of diverticular disease in oxford cohort of European prospective investigation into cancer and nutrition (EPIC): prospective study of British vegetarians and non-vegetarians. BMJ. 2011;343:d4131
12. Lahat A, Avidan B, Sakhnini E, et al. Acute diverticulitis—a decade of prospective follow up. J Clin Gastroenterol. 2013;47:415–419
13. Feuerstadt P, Das R, Brandt LJ. Diverticular disease of the colon does not increase risk of repeat C. difficile infection. J Clin Gastroenterol. 2013;47:426–431
14. Sharara AI, El-Halabi MM, Mansour NM, et al. Alcohol consumption is a risk factor for colonic diverticulosis. J Clin Gastroenterol. 2013;47:420–425
15. Beddy D, Wolff B. Advances and dilemmas in diverticular disease: surgery for recurrent diverticulitis. J Clin Gastroenterol. 2011;45:S74–S80
16. Humes DJ, Solaymani-Dodaran M, Fleming KM, et al. A population-based study of perforated diverticular disease incidence and associated morality. Gastroenterology. 2009;136:1198–1205
17. Boynton W, Floch MH. New strategies for the management of diverticular disease: insights for the clinician. Therapeutic Adv Gastroenterol. 2013 (In press)
18. Strate L, Modi R, Cohen E, et al. Diverticular disease as a chronic illness: evolving epidemiologic and clinical insight. Am J Gastroenterol. 2012;107:1486–1493
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