212. Jepsen S, Klaerke A, Nielsen PH, et al. Negative effect of metoclopramide in postoperative

adynamic ileus. A prospective, randomized, double blind study. Br J Surg 1986;73(4):290–291.

213. Lykkegaard-Nielsen M, Madsen PV, Nielsen OV. Ceruletide vs. metoclopramide in postoperative

intestinal paralysis. A double-blind clinical trial. Dis Colon Rectum 1984;27(5):288–289.

214. Cheape JD, Wexner SD, James K, et al. Does metoclopramide reduce the length of ileus after

colorectal surgery? A prospective randomized trial. Dis Colon Rectum 1991;34(6):437–441.

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216. Toyomasu Y, Mochiki E, Morita H, et al. Mosapride citrate improves postoperative ileus of patients

with colectomy. J Gastrointest Surg 2011;15(8):1361–1367.

217. Xie Q, Zong X, Ge B, et al. Pilot postoperative ileus study of escin in cancer patients after colorectal

surgery. World J Surg 2009;33(2):348–354.

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400 cases. Dis Colon Rectum 1986;29(3):203–210.

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Gastrointest Endosc 2006;64:279–282.

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Chapter 50

Crohn Disease

Scott R. Steele and Eric K. Johnson

Key Points

1 Crohn’s occurs anywhere along the gastrointestinal (GI) tract from mouth to anus and may present

with one or more disease patterns – fistulizing, inflammatory, and fibrostenotic.

2 The indications for operating on Crohn disease involve managing complications of the disease, not

cure.

3 Consider the patient’s disease state and medical therapy for Crohn disease in the decision-making for

surgery – this may require concomitant diversion in this patient population.

4 Whenever possible, preserve length of the small intestine and avoid extensive resections when not

required.

5 Similar to ulcerative colitis, Crohn disease is associated with an increased long-term risk of

developing colorectal cancer compared to the general population.

6 Asymptomatic Crohn disease (e.g., perianal fistula) does not necessarily require treatment.

7 Crohn disease is associated with a propensity for loose bowel movements and nonhealing wounds.

Think of function first when treating perianal disease, and avoid overaggressive procedures on the

sphincter that may alter continence.

INTRODUCTION

1 While many have heard the renowned account that Crohn disease derives its eponymous name more

from the alphabetized listing of its authors (Crohn, Ginzburg, and Oppenheimer) in the 1932 JAMA

publication “Regional ileitis: a pathological and clinical entity,”1 some may not realize that it was a

surgeon, Dr. A.A. Berg, who’s patients and idea it was to evaluate the original 52 specimens.2

Furthermore, the initial description of the condition was actually first made in 1769 by an Italian

physician Giovanni Battista Morgagni – he of the anal columns, aortic sinus, and congenital

diaphragmatic hernia fame.3 Much has changed since then, and continues to evolve in the understanding

and treatment of this idiopathic, ulcerogenic, inflammatory condition of the gastrointestinal (GI) tract.

Therefore, where many students and physicians alike are quick to cite Crohn facts such as its ability to

occur anywhere along the alimentary tract, has no “curative” operation, and is hallmarked by periods of

flares and quiescent disease, what is often forgotten is that three-quarters or more of all patients will

require at least one operation during their lifetime.4 Therefore, not only must the problem at hand be

addressed, but also the patient’s future function should be carefully weighed when considering the

proper therapeutic endeavor. Surgeons also need to be exceedingly aware of the indications, surgical

options, and expected outcomes for patients with Crohn disease, as well as have a thorough

understanding of the principles guiding both medical and surgical care to maximize outcomes. This

chapter will review the pertinent information regarding the background, diagnostic evaluation, and

treatment modalities for Crohn disease.

EPIDEMIOLOGY

Traditionally, Crohn disease is said to have a bimodal distribution with regard to age of onset, initially

in the second and third decades, followed by a later, albeit smaller, peak in the sixth decade.5 More

recently, systematic reviews have found an annual incidence of Crohn disease ranging from 20.2 per

100,000 person-years in North America and 12.7 per 100,000 person-years in Europe to 5.0 person-years

in Asia and the Middle East.6 Even within regions, variations exist – the incidence in western Europe is

almost twice that of eastern Europe, whereas the highest incidence of inflammatory bowel disease in

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the world is in the Faroe Islands. While data in developing countries remain relatively sparse, both the

incidence and prevalence of Crohn disease are increasing in the United States and around the world.

There is also an association with latitude, with increased incidences in higher latitude areas (i.e.,

Canada, Scandinavia, and Australia) compared to those closer to the equator. Males and females tend to

be affected equally, though whites and certain ethnic groups such as those of Ashkenazi Jewish descent

have higher overall rates.7

Although Crohn disease is not inherited through traditional Mendelian genetics, there does appear to

be a familial predisposition. A positive family history in patients with Crohn disease occurs in 2% to

14%.8 Closer examination reveals an approximate 5% age-adjusted lifetime risk of a first-degree relative

of a Crohn disease proband developing IBD (up to 8% for those of Jewish ancestry).9 On the other hand,

the concordance rate for monozygotic twins ranges from 20% to 50%,10 suggesting that genetics do play

a role and that the disease is not entirely dependent on environmental and/or acquired factors.

Furthermore, there does not appear to be a genetic concordance with regard to phenotypical

manifestations (i.e., fibrostenotic, fistulizing, phelgmonous or extent of disease) among relatives.

ETIOLOGY

Despite tremendous progress in the overall understanding of the disease and advancements in the

comprehension of the various phenotypical manifestations, the exact etiology of Crohn disease remains

unknown. Most hypotheses suggest there involves interplay among the genetic makeup of the individual

along with environmental, bacteriologic, immunologic, and epidemiologic factors that contribute to its

development. Efforts in each of these areas continue in attempt to determine which are causative factors

versus those that are simply associations.

Current theories revolve around the host–microbiome interaction, and the variable response that

occurs along several pathways that may ultimately lead to the chronic inflammatory state seen in

Crohn’s.11 In this model, intestinal microorganisms initiate an inappropriately regulated host immune

response that results in a cascade of events ranging from altered permeability of the intestinal lumen to

autoimmune “attacks” on several host organ systems.12 The fecal and intestine mucosal bacterial makeup is also known to be altered in Crohn disease patients; however, it is unknown if this occurs as a

result of the inflammatory process, or is itself a contributing factor to disease development.13 Proteomic

and metagenomic evaluation of commensal and altered GI microbiotia in Crohn patients indicates that

there is an inappropriate pattern recognition with the microbiotia serving as the driver of the disease

pathogenesis.14

Beginning in 1996, linkage studies of the human genome have helped with the discovery of several

IBD genes that signify patients who are susceptible to Crohn disease development.15 Most attention has

revolved around the NOD2 (formerly CARD15) gene on chromosome 16, a region felt to be involved

host interactions with bacterial lipopolysaccharide.16 Genetic differences in the pattern-recognition

proteins for which NOD2 codes may lead to an impaired sensing and handling of bacteria by the

immune system, disrupting the tenuous balance of normal tolerance versus initiating an incorrect

immune response. Since then, genome-wide association studies have provided insight that

polymorphisms in genes such as the ATG16L1 and IRGM play a role in autophagy in Crohn patients.

This process involves the regulation of cell development and differentiation, senescence, and ultimately

the inflammatory system response to what the body deems is normal and abnormal.17 In addition, other

genes such as TLR4, HLA, and IRF5 are involved in the innate and adaptive immune system response

seen in Crohn patients. Other causative immune factors have included overexpression and dysregulation

of tumor necrosis factor, an imbalance between proinflammatory and anti-inflammatory cytokines, and

an impaired mucosal susceptibility in sampling gut antigens.18 Combined, these all contribute to

regulatory mechanisms that may be altered and play a role in Crohn disease pathogenesis.

Infectious theories also continue to exist, 19 with specific organisms including Mycobacterium avium

subspecies paratuberculosis (i.e., Johne disease), Campylobacter concisus, adherent-invasive Escherichia coli

(AIEC), and non-H. pylori Helicobacter species among the most common agents cited. Although the

beneficial effects of antibiotics in the treatment of Crohn disease provide indirect evidence for a

bacterial etiology, no distinct organism has been identified to date. Similarly, several viruses have been

postulated to have an association with Crohn disease, the most common being EBV, CMV, and measles.

However, systematic reviews have found little evidence to support this notion.20 Additionally,

environmental factors are felt to play a role, highlighted by the well-established link to smoking with

both an increased susceptibility and worsened clinical course. Finally, while patients with Crohn disease

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