Inflammatory Bowel Disease
Inflammatory bowel disease (IBD) is the broad term that encompasses Crohn disease (CD), chronic ulcerative colitis (UC), and indeterminate colitis. Regardless of which specific disease entity is present, the pediatric surgeon and physicians caring for the patient are faced with difficult medical and surgical challenges. Clinical, radiographic, and pathologic features typically distinguish CD from UC. However, in up to 25% of patients with IBD, the diagnosis cannot be specified, leading to a diagnosis of indeterminant colitis.1 While medical therapies for all variants of IBD share similar strategies, the surgical care is driven by very different philosophical foundations. The surgical approach to UC is one of curative extirpation, rendering the patient free of disease through the removal of the affected intestine, generally with a proctocolectomy. The philosophy directing the operative approach to CD is much more humble, and is centered on treating the complications, but without cure. The fact that intervention is not curative must be communicated very clearly to families and patients prior to operation for CD, as the child will likely remain on medical therapy after the procedure and may require further surgical treatment at some point in the future.
Ulcerative Colitis
UC is a mucosal-based inflammatory disease limited to the colon, and has a risk of malignancy.2 The understanding that UC could be cured by removal of all colonic mucosa led to the development of operative treatment using total colectomy and proctectomy. The surgical approach has progressed from proctocolectomy with permanent ileostomy to restorative proctocolectomy, and is now routinely performed with minimally invasive techniques with or without a protective temporary ileostomy.3
Epidemiology
UC was described first in 1875 by Wilks and Moxon in the classic ‘Lectures on Pathologic Anatomy’.4 UC is predominantly diagnosed after the second decade of life. However, UC is being seen in increasing frequency in younger patients, with as many as 20% of patients becoming symptomatic before the age of 18 years.5 The incidence of UC has reportedly increased over the past three decades, and is currently reported to occur in 3.1 children per 100,000.6 Males and females are diagnosed with equal frequency. Western and Jewish societies are diagnosed with UC four times more frequently than Eastern cultures and developing countries, although this finding seems to be changing recently.7,8
Etiology
While there is much research surrounding UC and strides have been made in its underlying mechanisms, the exact etiology remains unclear.9,10 Myriad theories have been proposed including infectious etiologies, genetic relationships, immunologic disturbances, and psychologic factors. To date, none of these, either independently or in combination, has adequately explained the disease. However, each of these factors may account for certain characteristics of the disease. The genetic relationship helps to explain the racial and ethnic distribution of the disease. For instance, the relative risk for siblings with disease is 16%,11 and patients with extraintestinal manifestations have a high incidence of expression of the major antigen HLA-W27.12 Also, antineutrophil cytoplasmic antibodies have been associated with UC. Unfortunately, evidence that these are present in unaffected family members of UC patients raises doubt about the relationship.13,14 Finally, there are genetic predictors of disease severity. Recently, NOD-2insC polymorphism has been linked to worse outcome in patients following ileoanal pull-through.15 Additionally, a single nucleotide polymorphism in chromosome 4q27,16 and mucin abnormalities have been implicated in poor outcomes in UC patients.17
An infectious etiology for the basis of UC has become a rich area for investigation as evidence increases that the balance of microbial flora plays a key role in the regulation of the normal healthy intestine.18,19 While the balance of bacterial flora may have a critical role in UC, there does not appear to be a specific infectious agent that is responsible for causing the disease.
Since UC is primarily a disease of autoimmune dysregulation, it is logical that investigation would center on the immune function of those affected. The mucosal T-cell and its regulation is the primary target of immunologic research. In addition, cytokine expression is another area of active interest. Interleukin (IL)-1, IL-6 and IL-1 receptor agonists all show imbalances in the UC population.20
Pathology
UC is a mucosal-based chronic inflammatory process that involves the rectum and extends proximally to include varying amounts of colon, often in a contiguous fashion.21 The rectum is essentially always involved, and in cases of pancolitis, the rectum is usually the most severely affected. The characteristic microscopic findings include acute inflammation with crypt abscesses, mucosal bridging, and pseudopolyp formation. As the disease becomes more chronic in nature, the thin, distended colon becomes thickened, stiff, and foreshortened.
Clinical Presentation
As noted previously, UC is most commonly diagnosed in young adults, but 4% have onset of symptoms before age 10 years and 17% present between ages 10 and 20 years.22 The initial presentation is one of persistent diarrhea, progressing to hematochezia with mucus and purulence in the stool. Tenesmus, anorexia, weight loss, and growth retardation are also common (Box 41-1). As the disease becomes more chronic, children may exhibit signs of depression and withdrawal from social and physical activities. Emotional stress has been identified as a precipitating factor in patients with relapsing disease.23 Most patients experience chronic colitis with periods of quiescence and episodic recurring exacerbations. Only a small fraction (10%) of patients have a single exacerbation followed by longstanding remission. Unfortunately, as many as 80% of children become refractory to medical therapy, and ultimately require colectomy. Fifty per cent of children diagnosed with UC in childhood will require a colectomy before age 18 years.24
In about 15% of children, the presentation is fulminant with profuse bloody diarrhea, severe cramping, and abdominal pain, fever and sepsis. Aggressive medical management will control these symptoms initially in most cases; however, 5% of patients will require urgent colectomy in the face of toxic megacolon.25
Colorectal carcinoma has been reported to occur in 3% of patients in the first ten years after the initial diagnosis, and the incidence increases to 20% per decade after the first decade. Quiescent disease does not protect from the development of cancer. In fact, young age at initial UC diagnosis may be a risk factor for colorectal carcinoma.26–28
The extraintestinal manifestations of UC are outlined in Box 41-1 and occur in 60% of children.29 Growth retardation and delayed bone growth is associated with the chronicity of inflammation in UC, while delayed sexual maturation has been shown to be related to low gonadotropin levels.30,31 Since chronic inflammation has direct effects on growth and development, adequate control of disease can relieve the growth complications that would otherwise develop.32 Arthralgias occur in about a quarter of UC patients and the knees, ankles and wrists are the most commonly affected joints. The joint symptoms often complicate the diagnostic evaluation, and may cause the child to be erroneously diagnosed with rheumatoid arthritis before the gastrointestinal symptoms become obvious.
Erythema nodosum occurs primarily on the trunk and manifests as tender, red, subcutaneous nodules. Pyoderma gangrenosum is usually seen on the lower legs and presents as chronic deep ulcerations of the skin. Although much more common in adults, both may occur in children and usually resolve with treatment of the primary disease.33
Liver function testing is associated with abnormalities in up to 10% of children with UC. When abnormal liver function is identified, the patient requires close observation for the possible manifestations of primary sclerosing cholangitis.34 Anemia is common and is usually due to blood loss in the stool, but may also be related to anemia of chronic disease. Osteoporosis and malacia may be related to decreased calcium absorption associated with poor absorption of fat-soluble vitamins and/or to increased urinary loss from chronic glucocorticoid therapy. Nephrolithiasis can develop and is likely due to chronic oliguria related to inadequate intake and increased water loss in the stool.
The emotional and psychological ramifications of UC should not be dismissed. Those caring for these children will spend a great deal of time counseling, supporting, and encouraging them, and the care team should include a mental health care worker.35
Diagnosis
Although work continues on many potential candidates, serum markers for IBD have not proven to be reliable as yet. Perinuclear antineutrophil cytoplasmic antibody (pANCA) has been shown to be specific for UC and absent in controls. However, it is not predictive of disease severity or course.36 Pancreatic autoantibodies, such as NOD2/CARD15 and PAB, have also been shown to correlate with disease.37
The improved visualization and characterization of disease found on computed tomography (CT) and magnetic resonance imaging (MRI) have enhanced their accuracy, and these two imaging modalities have replaced the contrast enema as a diagnostic standard.38–41 Characteristic findings have been described as a ‘lead pipe’ appearance to the colon, loss of haustral markings, and a narrow lumen (Fig. 41-1). Pseudopolyps can develop in chronic UC and may be seen on both imaging studies. Upper gastrointestinal series are only helpful to assist in differentiating UC from CD with small bowel disease.
FIGURE 41-1 This 13-year-old child has chronic ulcerative colitis and will undergo proctocolectomy and ileal pouch–anal anastomosis. This coronal CT image shows a ‘lead pipe’ appearance to the descending colon with diffuse thickening of the colon wall and a very narrowed lumen (arrow). There is also significant thickening of the wall of the cecum and ascending colon (asterisk).
Medical Management
Maintenance therapy for UC is based on immunosuppressive and anti-inflammatory strategies. Treatment algorithms are based on severity of disease. Mild disease can often be controlled with 5-ASA (aminosalicylic acid) preparations such as sulfasalazine or mesalamine. Although it has not been proven to be beneficial, metronidazole is frequently added to this regimen.42 Moderate disease requires a more aggressive medical regimen to attain remission. In general, 5-ASA medications are used in conjunction with glucocorticoids, with or without 6-mercaptopurine or azathioprine. The prolonged use of steroids has severe implications, especially for children. Therefore, alternate forms of therapy are appropriate to avoid steroid dependence.43
Severe exacerbations are treated with bowel rest, intravenous fluid resuscitation or nutrition, and antibiotics. Although less frequently seen than mild or moderate disease, a small number of patients will present with acute, fulminant colitis that in some cases is associated with pancolitis and sepsis. Toxic megacolon refers to this acute, fulminant, septic colitis with massive distention of the entire colon. It is usually manifested by a distended air-filled transverse colon on plain films. High dose parenteral steroids are generally started, and cyclosporine and antitumor necrosis factor (TNF) antibodies should be considered. The approach to these patients is one of ‘rescue therapy,’ with the ultimate rescue therapy being achieved by colectomy.44,45 Perforation is an absolute indication for emergent operation, but failure to improve must be reviewed critically and objectively by the entire team to avoid allowing these children to become too sick prior to surgical intervention.
A multidisciplinary approach to the care of these children, including medical and surgical specialists, a psychologist, social worker, and nutrition specialist, is valuable in monitoring the course of therapy. Nonoperative therapy can have morbidity as well as malnutrition, growth failure, delayed sexual maturation, poor control of inflammation with persistence of symptoms, and psychological complications related to frequent stooling, fatigue, and the side effects of medications. Additionally, the immunomodulating medications that are currently most effective for controlling IBD carry their own risk of malignancy, primarily lymphoma.27 A multidisciplinary team is less likely to become invested in a specific form of therapy, and more willing to consider alternatives than a single provider working in isolation.
Surgical Management
The understanding that UC is limited to the colon, and is cured by removing the colon, has led those caring for children with this disease to consider earlier operation. In the past, the morbidity associated with proctocolectomy and permanent ileostomy was responsible for delay in seeking surgical options until after the child was severely ill and undernourished, and carried significant operative risk. As operations have become less morbid and more refined, and are associated with a better lifestyle afterwards, the threshold for colectomy has become more relaxed. Currently, operative alternatives are considered safe and effective when compared to medical therapies. With this in mind, they should be seriously considered in all children with UC, but especially those that are not responding adequately to the medical therapies. Although already mentioned, it is important to emphasize that the chronic inflammatory state of the intestinal mucosa is a risk factor for development of cancer, and youth does not protect against this risk.26–28
Preoperative Considerations
Once a decision is made for operative intervention, the preoperative preparation is important. Nutritional deficiencies must be addressed and may require a delay in the operative procedure, assuming an emergency operation is not needed. A reduction in immunosuppressive medications may be possible, although recent evidence suggests that immunosuppression is not necessarily associated with worse surgical outcomes.46 The use of a preoperative mechanical bowel preparation was once considered standard, but has recently been questioned.47–49 Currently, the need for mechanical bowel prep for colorectal surgery is not supported by the literature, although some authors continue to use it as part of their preoperative preparation. If a mechanical bowel prep is used, careful attention must be paid to the fluid and electrolyte status during the prep, as children are prone to dehydration.
Operative management of UC has undergone tremendous progress over the past 100 years. The earliest treatment was diversion with sigmoid colostomy. Later, ileostomy alone was advocated. These diversions accomplished little for the inflamed colon, and it was not until the 1940s that total colectomy was attempted. Unfortunately, there were countless ileostomy stomal complications until Brooke described the everted stoma that today bears his name.50 This technical modification allowed patients to enjoy a functional stoma, although the fluid and electrolyte derangements associated with an ileostomy continued to pose problems.
In 1947, Ravitch and Sabiston reported a restorative procedure that utilized the mucosectomy technique.51 Although this report documented the possibility of a restorative procedure, their results were sufficiently complicated to cause others to search for alternative approaches. Hence, various catheterizable pouches and stomas became the standard form of treatment after total colectomy, with or without proctectomy, and remained so until Martin described an adaptation of Soave’s endorectal pull-through used for Hirschsprung disease.52 The results following Martin’s adaptation for UC were significantly improved, but were still associated with significant issues related to stooling frequency and incontinence.53 Subsequent investigators have described differing pouch structures in attempt to create a reservoir to reduce stool frequency and continence.54–58 The current operative techniques for restorative proctocolectomy have resulted in significantly improved outcomes, and the current debate is centered on the issues outlined in Table 41-1.
TABLE 41-1
Current Issues Surrounding Operative Intervention in Ulcerative Colitis
| Issue | Advantages | Disadvantages |
| Laparoscopy (compared with open) | Reduced time of recovery, less adhesions, improved scarring, less pain | Advanced laparoscopic skills needed |
| Mucosectomy (compared with stapled ileorectal anastomosis) | Complete resection of mucosa, no future surveillance | Higher incidence of incontinence and soiling rate, need for hand-sewn anastomosis |
| Pouch (compared with straight pull-through) | Improved reservoir, decreased stooling frequency and soiling, especially after operation | Pouchitis, requires surveillance |
| Temporary stoma (compared with single stage operation) | Fewer early postoperative complications | Second operation for closure |
Elective Operation
The goal of all operative interventions for UC is to render the patient free of disease with the best possible functional outcome. The quality of the outcome is determined by the patient and family, as well as the clinical situation. However, the goal in most instances is restoration of nearly normal anatomy and function.
While the philosophical goals for the surgical management of UC have not changed in the past 50 years, the operative approaches have continued to be refined. Table 41-2 outlines the advantages and disadvantages of a single operation versus a staged approach. The experience and familiarity of the treating surgeon with these various approaches directs much of the decision-making process. The first procedure described to have good functional results was the straight ileal pull-through.59 However, the straight pull-through procedure is known to be associated with persistent high–pressure peristaltic contractions associated with urgency and soiling.60 Due to this problem, most surgeons have avoided the ileal pull-through and have opted for creation of an ileal reservoir, of which the J-pouch is the most common.
