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Extracolonic Manifestations

3 Proctocolectomy can help with some of the extracolonic manifestations, though PSC, pyoderma

gangrenosum, and ankylosing spondylitis specifically do not respond to surgery. Proctocolectomy has

shown to help with erythema nodosum, and small/large joints arthralgia, though the role of colectomy

is not completely defined in the treatment of extraintestinal manifestations of UC.85

Figure 66-6. Brooking ileostomy.

Surgical Management

Unlike CD, proctocolectomy is curative for gastrointestinal UC. As the disease begins in the rectum and

involves the colon proximally for a variable distance, ultimately proctectomy should be performed for

definitive treatment of UC.

Multiple surgical options are available, with treatment dependent on the urgency of presentation, and

general condition of the patient. Currently, in emergency conditions, the operation of choice is a

subtotal colectomy with preservation of the rectum, and a Brooke ileostomy (Fig. 66-6). Resection of

the rectum in the emergent setting should be avoided if possible, to both to allow continent

reconstruction at a later time and to avoid a perineal dissection in suboptimal conditions. Mobilizing the

rectum unnecessarily in emergent conditions disrupts the presacral planes, and will make later

reconstruction more difficult. In addition, the ureters and pelvic nerves are put at risk. Additional

consideration should be given to the level of ileal transection proximally, keeping in mind that a later

ileal pouch reconstruction is dependent on the ileocolic arterial arcade, and thus all efforts should be

made to keep this vascular network intact.

Abdominal Colectomy with a Brooke Ileostomy

The location of stoma should be marked preoperatively with the help of an enterostomal therapist if at

all possible. Managing a poorly placed stoma is a major source of frustration for the patient

postoperatively. Additionally, appropriately training and educating the patient preoperatively with

regard to the care of their stoma is critical to their postoperative progress.

4 A minimally invasive approach should be attempted if the patient is stable and the surgeon is

sufficiently comfortable with the operation.86,87 A systematic technique should be employed, and with

sufficient training and experience excellent outcomes can be achieved.88

The operation is started in the lithotomy position. If there is a concern regarding visualization of the

ureters, it is recommended that ureteral stents be placed. Though they do not reduce the rate of ureter

injury, they do help identify an injury immediately, and facilitate prompt repair.89 The colon is

mobilized in a lateral to medial fashion most commonly (Figs. 66-7 and 66-8), and unless there is

concern of dysplasia/neoplasia, the vessels (ileocolic, middle colic, and inferior mesenteric artery

branches) can be transected distally, facilitating safer mobilization. Particular attention should be paid

to the splenic flexure, as a splenic tear will unnecessarily complicate the operation.

Once the colon has been completely mobilized and the vessels have been divided, the distal ileum can

be transected. Particular attention must be paid to the integrity of the ileocolic vessel arcade, as the

subsequent ileal pouch construction is largely dependent on these vessels. The colon can then be

extracted through the ileostomy site, or through either a low vertical midline or a Pfannenstiel incision.

The terminal ileum can then be extracorporialized and a Brooke ileostomy can be constructed (Fig. 66-

6). It is critical to make sure that the small bowel mesentery is not twisted before “brooking” the

ileostomy.

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Figure 66-7. Colon mobilization. A: right colon. B: transverse colon. C: left colon.

Figure 66-8. Mobilized colon with vessels divided, and stapled at the rectum. This specimen is ready for extraction; the ileum can

be transected intracorporeally, or after specimen is extracorporealized.

Proctocolectomy with Brooke Ileostomy

Abdominal colectomy is performed as above. In cases of rectal dysplasia or cancer, a total mesorectal

excision is necessary. Patient is placed in Trendelenburg position and all bowel is displaced in the upper

abdomen. The sigmoid and rectum are placed on tension, and any adhesions are freed. If the uterus and

ovaries prevent visualization or adequate dissection, they are affixed in place by passing a 0-Prolene

stitch through the abdominal wall, through the uterus, and back through the abdominal wall. Retracting

the uterus anteriorly will help with visualization and dissection in the plane posterior to the vagina. The

rectal mobilization is commenced by placing the rectum on cephalad and anterior traction. The

peritoneum on the right of the rectum, medial to the ureters and the pelvic nerves is incised. This

embryologic plane is followed cephalad just posterior to superior rectal artery along its course, tracing

it proximally to the inferior mesenteric artery (IMA). Careful dissection just posterior to the IMA

pedicle toward the left pelvic sidewall will reveal the left ureter; its location is almost always higher

than expected. Lateral (on the left) to the ureter, the gonadal vessels are found. The ureter is

retroperitoneal, and as such all efforts should be made to avoid incising the retroperitoneum, and

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instead, it is safer if this embryologic layer is left undisturbed. Following this shiny layer superiorly,

one can easily carry the dissection cephalad until the IMA is identified and skeletonized. In the absence

of neoplasia, it is unnecessary to perform a high (proximal) ligation of the IMA, though by doing so,

one simplifies the dissection. Once the IMA (or the left colic artery) is identified and skeletonized, it can

be divided with the appropriate instrument, after making sure that both ureters are well out of the field.

Carrying the pelvic dissection distally, the pelvic nerves and the ureters should be clearly identified

and protected. Meticulous dissection can be done relatively bloodlessly. During anterior dissection of

the rectum, all effort should be made to continue the dissection posterior (on the rectum side) of the

Denovilliers fascia, specifically in men, to avoid sexual dysfunction. Similarly, during posterior

mobilization of the rectum particular attention should be given to identifying the presacral fascia, as

dissection posterior to this layer puts at risk the presacral vessels which can result in troublesome and

sometimes life-threatening bleeding. Once the dissection is carried out to the pelvic floor

circumferentially, a clamp can be placed on the proposed transection site, and the distance from the anal

verge can be assessed by a simple digital rectal examination. If the distance is appropriate then the

perineal dissection can follow. The patient is placed in Trendelenburg position, with both feet raised to

afford exposure to the perineum. The dissection plane starts in the intersphincteric plane. This dissection

leaves the external sphincter in situ, and can be incorporated in closing the perineal incision, which

decreases the complication rate. This intersphincteric plane is followed proximally and circumferentially

with particular attention anteriorly, to avoid injury to the vagina in women and urethra in men. Once

the intra-abdominal plane is reached, this part of the dissection is done.

Figure 66-9. Distal rectal transection, (A) stapled above the dentate line, or (B) a mucosectomy in preparation for a hand-sewn

anastomosis.

Proctocolectomy with Ileal Pouch-Anal Anastomosis (IPAA)

5 The colectomy and rectal mobilization are performed as above, however, once one reaches the pelvic

floor the rectum is transected approximately 1 cm above the anorectal ring with the stapler (Fig. 66-

9A). This rectal cuff will allow for better function, but will require surveillance as it is at risk for

cuffitis, and neoplasia. Alternatively, a mucosectomy can be done (Fig. 66-9B) with a subsequent handsewn IPAA anastomosis, though this is mostly done in cases of distal neoplasia, and poorer function is

observed.

Once the proctectomy is finished, a pouch is fashioned from the terminal ileum. Multiple

configurations are possible; the J-pouch configuration is the most popular in the United States (Fig. 66-

10). This is constructed by first aligning the terminal ileum into a J-configuration. It is necessary for the

apex of the pouch (the end connection of the pouch to the anus) to reach the rectal cuff or anus.

Usually, if the apex can be stretched without tension beyond the symphysis pubis, the pouch should

reach the anastomosis site without undue tension. Multiple maneuvers can be done to “lengthen” the

reach of the pouch, and are beyond the scope of this discussion. The pouch is usually between 10 and 20

cm in length, and ultimately optimizing reach has some effect on how long the pouch is. Once the apex

location is decided on, the two limbs of the ileum are aligned with interrupted suture. An enterotomy is

made at the apex of the pouch, and a stapler is used to fashion a common channel between the two

limbs of ileum. The pouch can then be attached by using an EEA stapler device (placing the anvil in the

J-pouch, and firing pin through the rectal pouch), or by performing a hand-sewn anastomosis (Fig. 66-

11).

1718

Figure 66-10. IPAA construction and anastomosis. (A) terminal ileum alignment for (B) common channel creation. C: EEA anvil

attachment at the apex of the pouch.

Figure 66-11. Anastomosis of the J-Pouch with (A) stapled anastomosis and (B) hand-sewn anastomosis.

IPAA-Postoperative Complications

6 The majority of patients who have an IPAA report high quality of life. Small bowel obstruction occur

in up to 20% of patients, most commonly managed nonoperatively.90 The J-pouch is at risk for

postoperative abscess, fistula, and pelvic sepsis, which can occur anytime after the pouch formation.

Immediate intervention with drainage and antibiotic treatment to control the infection is key, as

prolonged infection puts the pouch at risk.91,92

Pouchitis is a nonspecific inflammation of the pouch that occurs in up to 40% of the patients.93 This is

the most common complication after IPAA. Pouchitis is treated initially with oral antibiotics. If

pouchitis does not resolve, pouch evaluation using endoscopy is undertaken, with pouch mucosa biopsy,

and further evaluations can include testing for infections, such as C. difficile. Other medications that

have shown to help treat pouchitis are corticosteroids, budesonide, 5-aminosalicylic acid, and

allopurinol.94

Corticosteroid use does not preclude IPAA construction, though a slightly higher rate of anastomotic

1719

leaks is observed, thus, usage of a diverting ileostomy should be considered in this patient population.95

The effect of preoperative use of anti-TNF agents is not clear and limited to nonrandomized studies.

Routine surveillance of the pouch for dysplasia is not essential, however, surveillance of the rectal

cuff or transitional zone is necessary (both stapled and hand-sewn anastomoses). The incidence of

carcinoma in the rectal remnant/anal transition zone is rare but reported.96

Proctocolectomy with Koch Pouch

This is the second continent option (in addition to IPAA). Only a few centers worldwide perform this

procedure, and the technique is beyond the scope of this chapter.

In summary, UC is an inflammatory bowel condition influenced by both genetic and environmental

factors. Its treatment includes increasingly sophisticated medical and surgical treatment regimens. An

individualized, multidisciplinary treatment approach should be employed for each patient, at an

institution that has the experience and volume to provide the most current and appropriate treatment.

References

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capability of improved soft tissue differentiation. Particularly in the last decade, developments in MRI

hardware and software has made this imaging modality an especially valuable tool in diagnosing and

following patients with UC (Fig. 66-4).51

Figure 66-2. A: Erythema nodosum. B: Pyoderma gangrenosum. (Reproduced with permission from Goodheart HP. A Photoguide of

Common Skin Disorders: Diagnosis and Management. Baltimore, MD: Lippincott Williams & Wilkins; 1999.)

Figure 66-3. Abdominal x-ray of Megacolon Beck DE, Roberts PL, Saclarides TJ, et al. ASCRS. New York, NY: Springer; 2011.

Ultrasound and nuclear medicine may provide complementary information in addition to CT and MRI

but are currently used less commonly and are utilized only for specific situations.

Endoscopy

Endoscopic evaluation is the most useful tool in diagnosing UC. Often the first step is a flexible

sigmoidoscopy or rigid proctoscopy especially in cases of acute flare, when a full colonoscopy may pose

a significant risk of perforation. The macroscopic appearance of the colon through the endoscopy can

often differentiate between UC and CD. Biopsies are taken, in addition to stool samples to rule out

bacterial pathogens and ova/parasites.

Pathology

Macroscopic Appearance

UC always starts in the rectum and progresses proximally (Fig. 66-5). Although UC is a mucosal and

submucosal disease, in the acute setting of severe disease, the colon wall can be inflamed transmurally,

mimicking CD.

The mucosa is involved in a confluent manner, and unlike CD, fibrosis and strictures are uncommon

(Table 66-2). Most importantly, the presence of stricturing disease in UC represents the potential for

malignancy, which must be excluded. Superficial fissures are common, as are pseudopolyps. On

occasion, the rectum can appear to be spared, especially if topical medication has been used through

enema or suppository.

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Figure 66-4. MRI demonstration of active UC with rectal wall thickening, increased vascularity, and inner layer

hyperenhancement. Courtesy of Dr. William Reed.

Microscopic Appearance

UC is an inflammatory process, thus neutrophil infiltration is common, and crypt abscesses form, which

then coalesce to form ulcers (Table 66-2). Goblet cell mucin depletion and crypt distortion are common

in UC. In long-standing UC, special attention must be given to the presence of dysplastic lesions, though

these can be difficult to identify in cases of acute inflammation.

Differential Diagnosis

Bloody diarrhea can be a symptom of an infectious process. It is important to rule out pathogenic

bacteria, parasites, and viruses. Clostridium difficile should specifically be excluded. Other infectious

agents include Salmonella, Escherichia coli (0157:H7 strain), Camphylobacter, and Entamoeba.

In nearly 10% of the cases, it is impossible to definitively classify the colitis. Over time, a portion of

these indeterminate colitis cases will separate as either Crohn’s or UC. However some will remain as

indeterminate, especially if the serology assessment is inconclusive (for both ASCA and p-ANCA).52

MANAGEMENT

Medical Management

Corticosteroids

Corticosteroids are frequently used as the primary rescue medication in treatment of acute flares of UC.

Corticosteroid efficacy in inducing remission approaches 70%.53,54 Lack of improvement or disease

progression with corticosteroid treatment is followed by biologic agent treatment (as a secondary

rescue medication) or surgery.55 Overall, the use of corticosteroids is decreasing, largely due to the

increase in the number and treatment effectiveness of the biologic agents available. Corticosteroids

should not be used for maintenance of remission due to their side-effect profile. Topical corticosteroids

such as budesonide or rectal preparations can be effective and have a reduced side-effect profile.

However, these medications are not typically used in the acute setting. The side-effect profile of

systemic corticosteroids includes osteoporosis, diabetes, glaucoma, and infections, among others. Longterm use of corticosteroids is associated with an increase in mortality.56

Aminosalicylic Acid Compounds (5-ASA)

These compounds are most commonly used as first line medications in treating mild UC, and can be

used in maintenance of remission. Concomitant use of oral and rectal preparation is effective in

maintenance of UC remission.57 Noncompliance with 5-ASA maintenance therapy is associated with a

fivefold increase in disease recurrence.58,59 Cases of nephrotoxicity have been reported with use of 5-

ASA, though these cases are rare. Folate must be supplemented with treatment of 5-ASA as its

absorption is impaired by 5-ASA.

Immunomodulators (Nonbiologic)

Cyclosporine can be used as an effective first-line or second-line rescue medication (e.g., after failed

corticosteroid treatment) and is currently used at a limited number of centers. It is most commonly used

as first-line treatment, and serves as an option for those patients recalcitrant to corticosteroid

treatment.60 Close monitoring of cyclosporine levels is necessary. Cyclosporine toxicity profile includes

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hypertension, renal failure, and infections.61

Figure 66-5. UC endoscopic findings with A: Loss of normal vascular pattern. B: Contact bleeding. C: Granularity. D: Ulceration

and friability. E: Colonic stricture. (Reproduced with permission from Corman ML. Colon and Rectal Surgery, 5th ed. Philadelphia,

PA: Lippincott Williams & Wilkins; 2005.)

Mercaptopurine (6-MP). 6-MP and its prodrug azathioprine are thiopurine analogs and have been used

extensively in the treatment of UC. They are superior to 5-ASA treatment alone and are often clinically

used in combination with either 5-ASA or anti-TNF drugs in treating IBD.62 Skin cancers and lymphoma

have been reported with thiopurine.63 Severe infections have been reported with use of these

medications.64 Liver enzyme elevations, pancreatitis, and cholestasis have also been seen, and the most

commonly reported side effects are headaches, hypersensitivity, and abdominal pain.

Methotrexate. This medication is rarely used in UC, more commonly used in CD, although its sideeffect profile makes its use difficult even in CD. Hepatotoxicity bone marrow suppression and central

nervous system side effects limit the use of this medication.65

Biologic Immunomodulator Agents

Infliximab is the first anti-TNF medication that was used in treatment of CD in 1988, then shortly after

became FDA approved for use in UC. Infliximab is chimeric mouse–human monoclonal antibody.

Infliximab has been found to successfully induce remission in over 60% of the UC patients treated in the

ACT 1 and 2 trials.66 Extended follow-up of the patients in the trial found that 15% of patients who

initially responded to infliximab subsequently had to discontinue therapy due to side effects or loss of

efficacy.67 Approximately 9% of patients continued to be treated with infliximab for 3 years.

Adalimumab, certolizumab, and golimumab were then added to the list of the anti-TNF agents, a list

that is continually growing. Both infliximab and golimumab have been efficacious in inducing and

maintaining remission in UC patients.66,68,69 Among the biologic agents’ side-effect profile, infection

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remains a persistent concern.70,71 The data regarding malignancy risk with anti-TNF agents are mixed;

there appears to be an increased risk of lymphoma.72

SURGERY

Indications of Surgical Intervention

2 Approximately 20% to 30% of patients that develop UC will ultimately need an operation.73,74

Indications for surgery include fulminant colitis, toxic megacolon, uncontrolled bleeding, neoplasia,

recalcitrance to medical management, unrelenting extraintestinal manifestations, and development of

significant side effects of the treatment medications.

Toxic Megacolon

This is a life-threatening, surgical emergency. Toxic megacolon (Fig. 66-3) is not specific to UC; it can

occur in cases of infectious collidities (C. difficile, Shigella, Salmonella, etc.), or ischemic colitis. Patients

present with systemic toxicity, heralded by high fever, tachycardia, severe abdominal pain, leukocytosis

or leukopenia, and a distended, thickened colon. Immediate, aggressive resuscitation and broadspectrum antibiotics should be started, and all opiates, and antidiarrheal agents should be ceased. An

infectious cause should immediately be ruled out as treatment for UC includes corticosteroids, treatment

which would be detrimental to the management of infectious colidities. Toxic megacolon is seen most

often in new cases of UC, but acute exacerbations of chronic UC can also lead to toxic megacolon.

Nonoperative treatment can be attempted, however, any signs of instability, worsening of the clinical

condition, or lack of improvement within 3 to 5 days should be followed by prompt operative

treatment. In one study, nearly half of all patients with UC treated nonoperatively subsequently

required surgery, most under urgent or emergent circumstances.75 In the contemporary era of biologic

options, failure can occur in up to 30% in the short term (within 30 days), and it is unclear in the long

term how many of these patients will need a colectomy, and under what clinical circumstances.76

Fulminant Colitis

Patients presenting with tachycardia, fever, and surgical tenderness need aggressive resuscitation.

Intravenous steroids should be started promptly, and the patients should be offered surgical treatment

immediately if their condition deteriorates. In general terms, patients should improve within 3 to 5 days

on medical therapy. Early surgical intervention has shown a clear decrease in the mortality rate in

patients failing medical therapy.77,78

Uncontrolled Bleeding

Less than 5% of the patients affected with UC have life-threatening bleeding. In this rare circumstance

an abdominal colectomy is necessary. These cases represent approximately 10% of the emergent

colectomies performed in UC.79

Carcinoma/Dysplasia

Stage for stage, cancer in the setting of UC has the same prognosis, however, cancer is often detected at

a later stage in UC. Nearly 20% of the patients with colorectal carcinoma in the setting of UC are

unresectable at the time of diagnosis.80,81 The highest risk of colorectal cancer (CRC) is seen in those UC

patients with a long history of pancolitis, a risk that accrues after 8 to 10 years of UC. The absolute risk

of CRC development is less than 8% after 30 years of UC.82 Patients with over 8 years of UC,

particularly with extensive colitis, should undergo colonoscopy yearly, or every 2 years.83 It is often

difficult to identify dysplasia in inflamed colon, and thus at the time of colonoscopy, random biopsies

are obtained in addition to sampling any polyps, adenomas, or dysplasia-associated mass or lesions

(DALM). Undetected synchronous cancer can coexist in areas of low- and high-grade dysplasia.84 Thus,

high-grade dysplasia, nonadenoma-like DALMs, and multifocal dysplasia are indications for

proctocolectomy, though there is ongoing research in this area.

Recalcitrance to Medical Treatment

Some patients do not respond fully to medical treatment, and either have persistent symptoms despite

maximal medical treatment, or respond only to corticosteroids, and are thus subject to the side effects

of long-term corticosteroid treatment.

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168. Medina C, Vilaseca J, Videla S, et al. Outcome of patients with ischemic colitis: review of fiftythree cases. Dis Colon Rectum 2004;47:180–184.

169. Scharff JR, Longo WE, Vartanian SM, et al. Ischemic colitis: spectrum of disease and outcome.

Surgery 2003;134:624–629.

170. Green BT, Tendler DA. Ischemic colitis: a clinical review. South Med J 2005; 98:217–222.

171. Chaer RA, Helton WS. Dieulafoy’s disease. J Am Coll Surg 2003;196:290–296.

172. Lee YT, Walmsley RS, Leong RW, et al. Dieulafoy’s lesion. Gastrointest Endosc 2003;58:236–243.

173. Gimeno-Garcia AZ, Parra-Blanco A, Nicolas-Perez D, et al. Management of colonic Dieulafoy lesions

with endoscopic mechanical techniques: report of two cases. Dis Colon Rectum 2004;47:1539–1543.

174. Veldhuyzen van Zanten SJ, Bartelsman JF, Schipper ME, et al. Recurrent massive haematemesis

from Dieulafoy vascular malformations–a review of 101 cases. Gut 1986;27:213–222.

175. Park CH, Sohn YH, Lee WS, et al. The usefulness of endoscopic hemoclipping for bleeding

Dieulafoy lesions. Endoscopy 2003;35:388–392.

176. Cheng CL, Liu NJ, Lee CS, et al. Endoscopic management of Dieulafoy lesions in acute nonvariceal

upper gastrointestinal bleeding. Dig Dis Sci 2004;49:1139–1144.

177. Romaozinho JM, Pontes JM, Lerias C, et al. Dieulafoy’s lesion: management and long-term

outcome. Endoscopy 2004;36:416–420.

178. Novitsky YW, Kercher KW, Czerniach DR, et al. Watermelon stomach: pathophysiology, diagnosis,

and management. J Gastrointest Surg 2003;7:652–661.

179. Nagy SW, Marshall JB. Aortoenteric fistulas. Recognizing a potentially catastrophic cause of

gastrointestinal bleeding. Postgrad Med 1921;93:211–212.

180. Ali AT, Modrall JG, Hocking J, et al. Long-term results of the treatment of aortic graft infection by

in situ replacement with femoral popliteal vein grafts. J Vasc Surg 2009;50:30–39.

181. Yahchouchy EK, Marano AF, Etienne JC, et al. Meckel’s diverticulum. J Am Coll Surg

2001;192:658–662.

182. Mackey WC, Dineen P. A fifty year experience with Meckel’s diverticulum. Surg Gynecol Obstet

1983;156:56–64.

183. Lichtstein DM, Herskowitz B. Massive gastrointestinal bleeding from Meckel’s diverticulum in a 91-

year-old man. South Med J 1998;91:753–754.

184. El-Haddawi F, Civil ID. Acquired jejuno-ileal diverticular disease: a diagnostic and management

challenge. ANZ J Surg 2003;73:584–589.

185. Rabeneck L, Paszat LF, Hilsden RJ, et al. Bleeding and perforation after outpatient colonoscopy and

their risk factors in usual clinical practice. Gastroenterology 2008;135:1899–1906.

186. Gibbs DH, Opelka FG, Beck DE, et al. Postpolypectomy colonic hemorrhage. Dis Colon Rectum

1996;39:806–810.

187. Halme L, Doepel M, von Numers H, et al. Complications of diagnostic and therapeutic ERCP. Ann

Chir Gynaecol 1999;88:127–131.

188. Vasconez C, Llach J, Bordas JM, et al. Injection treatment of hemorrhage induced by endoscopic

sphincterotomy. Endoscopy 1998;30:37–39.

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Chapter 66

Ulcerative Colitis

Dorin T. Colibaseanu and David W. Larson

Key Points

1 Ulcerative colitis is a form of inflammatory bowel disease (IBD) largely limited to the mucosa and

submucosa of the colon and rectum. This process is continuous, beginning at the rectum, and

extending proximally for a variable distance.

2 The acute indications for surgical intervention are fulminant disease, toxic megacolon, and bleeding.

Failures of medical management, dysplasia, or cancer are indications for elective surgery.

3 The intestinal manifestations of ulcerative colitis (UC) are cured by removal of the colon and

rectum.

4 Current surgical options depend on the acuity of presentation of the disease; minimally invasive

methods should be employed when clinically indicated and technically feasible.

5 Proctocolectomy with ileal pouch-anal anastomosis (IPAA) provides patients with a continent

reservoir; a Brooke ileostomy is available for those patients who do not qualify for a pouch

construction.

6 Although perioperative and late complications after ileal pouch-anal reconstruction are not

uncommon, the vast majority of patients enjoy a high quality of life after surgery.

INTRODUCTION

1 Ulcerative colitis (UC) and Crohn disease (CD) affect more than 1.4 million people in the United

States. Together these two diseases have many common characteristics, yet they are two distinct

entities.1 UC is a nonspecific and idiopathic inflammatory bowel disease (IBD) of unknown etiology that

primarily affects the mucosa and submucosa of the colon and rectum. It is characterized by recurring

episodes of inflammation. While medical treatment remains the mainstay of UC management, it does

not represent a cure.

EPIDEMIOLOGY

Determining the exact incidence of UC is difficult because mild cases might never be reported, and the

disease itself is uncommon. In North America, the reported incidence varies between 2.2 and 19.2 cases

per 100,000 person-years.1–5 Global incidence and prevalence of UC tends to be the highest along

northern latitudes, and lower in Asia and the Middle East.5–8 Over time, the incidence of IBD has

increased globally, especially the last 20 years.9,10

Etiology and Risk Factors

Development of UC is likely due to the interaction of multiple genes, and environmental factors. It is

more common in Jewish and Caucasian populations, and infrequent in black and Hispanic

populations.11,12

Genetics

Both environmental and genetic risk factors have been implicated in the development of UC; however,

the exact pathogenesis has not been fully elucidated. Up to 20% of the patients with IBD are part of

families with other afflicted members. It is recognized that there is a non-Mendelian genetic

predisposition to developing UC. Monozygotic twin concordance rate for UC varies between 10% and

19%, and it increases over time.13–15 The offspring of parents with UC can have a risk of developing UC

as high as 33%.16 Genetic concordance in CD is higher than in UC, and more than 100 loci have been

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associated with increased risk for developing IBD (Table 66-1).17–21 Major histocompatibility complex

HLA-DR2 is associated with UC, and there are at least 15 distinct loci that are associated with risk of

developing UC.22–25

Environmental Factors

There remains a bimodal distribution of UC, which typically develops between 15 and 40 years of age

and then in a smaller subgroup later in life between 50 and 80 years (Fig. 66-1).26 UC appears to be

slightly more common in men.27,28

Table 66-1 Genes Commonly Implicated in Ulcerative Colitis and Crohn Disease

Figure 66-1. Age-specific incidence of UC in Midwestern US population. (Adapted from Loftus CG, Loftus EV Jr, Harmsen WS, et

al. Update on the incidence and prevalence of Crohn’s disease and ulcerative colitis in Olmsted County, Minnesota, 1940–2000.

Inflamm Bowel Dis 2007;13:254–261.)

Diet rich in saturated fats, and refined sugar has been associated with higher incidence of UC.

Physical activity however, is not strongly associated to incidence of UC.29–31 Smoking appears to have a

protective effect for UC; conversely former smokers have an increased risk of UC compared to those

who never smoked.32–34 The apparent protective effect of smoking extends to some of the

extraintestinal manifestations of UC, in particular primary sclerosing cholangitis (PSC) and occurrence

of pouchitis.35,36 Interestingly, an appendectomy also has a protective effect from developing UC,

though the mechanism is essentially unknown. Large, retrospective studies have shown a protective

effect of 55% to 70%,37–41 especially if the findings at the operation were consistent with appendicitis or

lymphadenitis.39 The mechanistic theories proposed for this interesting finding include the notion that

as the body’s immune system responds to the inflammatory process of appendicitis, it adapts such that

the inappropriate inflammatory process that defines UC never occurs. The environmental risks for

development of CD and UC have some similarities but the diseases are in essence distinct entities (Table

66-2).

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CLINICAL FEATURES

UC symptoms parallel the degree of the disease. Typically, UC affects the rectum, extending proximally

in a continuous fashion, and can involve the entire colon. Most commonly the distal colon is involved

for various length, however, approximately 20% of the time, patients present with pancolitis.42 The

classic symptoms of UC are diarrhea, and rectal bleeding. Additional symptoms include tenesmus,

urgency, and colicky abdominal pain.43 Persistent pain is uncommon, and often can represent severe

disease with inflammation extending to the serosa.44 The sensation of constipation and incomplete

evacuation can occur if there is severe rectosigmoid inflammation and spasm. As the disease progresses,

systemic symptoms of fever, anorexia, weight loss, and malaise ensue. Severity of disease can be

calculated using the Mayo Severity Index Calculator (Table 66-3).45 Other calculators exist.

Extraintestinal Disease

Hepatobiliary

Approximately 3% to 5% of UC patients develop PSC. Generally, the patients are asymptomatic, though

as the disease progresses liver enzyme elevation, pruritus, fatigue, chills, and right upper quadrant pain

can develop. The risk of acquiring PSC is independent of colonic UC activity, and the risk persists after

proctocolectomy. In addition, PSC is an independent risk factor for developing dysplasia/cancer in

patients with UC.46

Ophthalmologic

Greater than 3% of patients with UC can develop iritis, episcleritis, or uveitis. Episcleritis severity can

parallel GI symptoms, but uveitis does not match GI disease activity. Though uveitis is less common, the

disease is more severe, and if not promptly treated can result in blindness. Topical steroids and

infliximab have successfully been used in treating UC uveitis.47

Table 66-2 Clinicopathologic Features of Ulcerative Colitis vs. Crohn’s

Table 66-3 The Mayo Severity Index

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Cutaneous

Manifestations of UC can include erythema nodosum and pyoderma gangrenosum (Fig. 66-2). Erythema

nodosum generally follows the disease progress of the GI symptoms, occurring in up to 4% of patients

with UC.48 These violet subcutaneous nodules can be treated with topical steroids, though most

commonly, systemic treatment of GI symptoms will also help with erythema nodosum. While pyoderma

gangrenosum occurs less frequently than erythema nodosum, its treatment is more difficult as the

disease course of pyoderma gangrenosum does not always parallel UC activity. Infliximab has shown

some promise in treating pyoderma gangrenosum.49

Musculoskeletal

These conditions are responsible for the most frequent extraintestinal complaints. Sacroileitis and

ankylosing spondylitis are associated with UC flairs, and remissions. Carriers of HLA-B27 are especially

prone to ankylosing spondylitis. Successful treatment of sacroiliatis with NSAIDs does not preclude

progression of spondylitis. Methotrexate has also been successfully used, and there are increasing data

of successful use of anti-TNF agents.50

DIAGNOSIS

Physical examination is often unrevealing, though generalized pain is often an indicator of severe

disease. A triad of tachycardia, fever, and leukocytosis are indicators for systemic toxicity and should

alert the clinician of impending need of surgical intervention. Vague discomfort, and perianal irritation

are common findings due to bowel movement frequency.

Imaging

Conventional x-rays can be useful in the rare cases of obstruction and/or perforation. The use of

contrast studies allow for the identification of signs of severe inflammation with loss of haustral

markings, although they have largely been replaced by more modern imaging modalities. Figure 66-3

shows distended colon with loss of haustral markings, concerning for toxic megacolon.

Abdominal computed tomography with oral and/or rectal contrast and CT enterography protocols are

the modern imaging techniques of choice and provide additional information regarding the severity of

disease. The presence of fistulas, phlegmon, mass, or abscess is an indication of a disease process other

than UC as these findings may in fact represent other diagnoses such as Crohn, diverticulitis, and cancer.

MRI has the advantage of limiting ionizing radiation exposure, benefiting the young especially, and

those that potentially may require multiple imaging studies over the years. Additionally, MRI has the

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few days to many years; the median interval is about 3 years.179 Most patients have an initial episode of

GI bleeding (i.e., herald bleed) that is followed in hours, days, or weeks by catastrophic hemorrhage.

Patients may also complain of back or abdominal pain and less commonly have fever or signs of sepsis

from infection of the graft.

The diagnosis of an aortoenteric fistula must be considered in any patient with an aortic prosthesis or

an abdominal aortic aneurysm who presents with GI hemorrhage. Endoscopy should be urgently

performed following resuscitation to disclose evidence of an aortoenteric fistula or another cause of

bleeding (e.g., peptic ulcer disease with stigmata of recent hemorrhage). If endoscopy fails to

demonstrate an aortoenteric fistula or another convincing source of bleeding and the patient is not

massively bleeding, computed tomography may be helpful in detecting perigraft infection or other

evidence of an aortoenteric fistula. In patients who are actively bleeding, exploratory laparotomy with

exposure of the proximal graft should be undertaken. Identification of an aortoenteric fistula or erosion

requires resection of the graft with extra-anatomical bypass and repair of the duodenal wall, or aortic

reconstruction using a variety of techniques such as aortic reconstruction with popliteal vein or human

allografts.180 The operative management of aortoduodenal fistulas is considered in greater detail in

Chapter 96.

Meckel Diverticulum

Bleeding from a Meckel diverticulum is a common cause of lower GI hemorrhage in children but is rare

in older adults. Meckel diverticula are present in approximately 2% of the population. The lifetime risk

of a complication from a Meckel diverticulum is about 4%.181 About 25% of patients with symptomatic

Meckel diverticula present with hemorrhage.182 In a series of 17 patients who bled from Meckel

diverticula, 11 experienced frank hemorrhage while 6 had chronic occult blood loss. The incidence of GI

hemorrhage is greatest in the first decade of life and steadily decreases from that point. In one series,

no patient older than 40 years of age, and only one patient older than 31 years, bled from a Meckel

diverticulum,182 although it has been reported in the very elderly.183 The pathogenesis of this bleeding

involves the occurrence of ectopic gastric mucosa with peptic ulceration of adjacent bowel wall.

Although these lesions may be demonstrated by enteroclysis, abdominal scintigraphy following the

intravenous injection of 99technetium-pertechnetate demonstrates the ectopic gastric mucosa within the

diverticulum, suggesting the correct diagnosis. Treatment consists of resecting the diverticulum with

adjacent bowel. Diverticulectomy alone will be associated with persistence of the ulcer and the

possibility of recurrent hemorrhage.

Small Intestinal Diverticulum

Diverticular disease of the small intestine is another uncommon cause of either UGI hemorrhage

(duodenal) or LGI hemorrhage (jejunoileal diverticula).184 The pathogenesis is similar to that of colonic

diverticula with erosion of a vasa recta through the diverticular wall and the acute onset of massive

hemorrhage. Depending on the location of the diverticulum, patients may present with either

hematemesis, melena, or hematochezia. Hemorrhage from this source can be a vexing diagnostic

problem because jejunoileal lesions are beyond the reach of the gastroscope and bleeding from duodenal

diverticula may be difficult to discern. Mesenteric angiography or intraoperative enteroscopy may

localize the site of hemorrhage in actively bleeding patients. Segmental resection of the involved

intestine is the treatment of choice.

Hemorrhage Following Endoscopic Procedures

Significant hemorrhage can occur following endoscopic biopsy, sphincterotomy, and other traumatic

procedures. Fortunately these complications are uncommon. Colonoscopy may rarely cause clinically

significant bleeding (0.1% to 0.2%).185 Biopsy of lesions increase the risk up to 10-fold. Usually this is

minor and self-limited and may occur up to 12 days after the procedure.186 The bleeding site can be

confirmed by tagged red cell scanning, arteriography, or colonoscopy. Arteriography and colonoscopy

can be used therapeutically as described previously. Endoscopically placed bands such as those used for

esophageal varices, have also been reported to be successful in arresting hemorrhage.98 Surgical

treatment is rarely required.

Hemorrhage following endoscopic biliary sphincterotomy occurs in approximately 2% of patients.187

Mild immediate bleeding is common and is usually self-limited. Late hemorrhage usually occurs within

48 hours of the procedure but can occur many days after sphincterotomy.188 More severe hemorrhage

can usually be controlled by epinephrine injection,188 making the need for operative treatment

1699

uncommon.

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complications in the United States from 2001 to 2009. Am J Gastroenterol 2012;107:1190–1195.

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and management of lower gastrointestinal hemorrhage. Gastrointest Endosc 1995;41:93–98.

8. Bramley PN, Masson JW, McKnight G, et al. The role of an open-access bleeding unit in the

management of colonic haemorrhage. A 2-year prospective study. Scand J Gastroenterol

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9. Longstreth GF. Epidemiology and outcome of patients hospitalized with acute lower gastrointestinal

hemorrhage: a population-based study. Am J Gastroenterol 1997;92:419–424.

10. Kok KY, Kum CK, Goh PM. Colonoscopic evaluation of severe hematochezia in an Oriental

population. Endoscopy 1998;30:675–680.

11. Kaplan RC, Heckbert SR, Koepsell TD, et al. Risk factors for hospitalized gastrointestinal bleeding

among older persons. Cardiovascular Health Study Investigators. J Am Geriatr Soc 2001;49:126–

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12. Fiaccadori E, Maggiore U, Clima B, et al. Incidence, risk factors, and prognosis of gastrointestinal

hemorrhage complicating acute renal failure. Kidney Int 2001;59:1510–1519.

13. Cheng HC, Chuang SA, Kao YH, et al. Increased risk of rebleeding of peptic ulcer bleeding in

patients with comorbid illness receiving omeprazole infusion. Hepato Gastroenterol 2003;50:2270–

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14. van Leerdam ME, Vreeburg EM, Rauws EA, et al. Acute upper GI bleeding: did anything change?

Time trend analysis of incidence and outcome of acute upper GI bleeding between 1993/1994 and

2000. Am J Gastroenterol 2003;98:1494–1499.

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particularly in patients who are massively bleeding or in whom colonoscopy was unrevealing or

incomplete. Characteristic angiographic findings include a densely opacified and slowly emptying,

dilated, tortuous vein (found in 90% of patients), a vascular tuft (seen in 66% to 75% of patients), and

an early-filling vein (usually a segmental vein in the cecum or right colon, although at times, it may be

the ileocolic vein).

The natural history of these lesions was revealed by the clinical course of 101 patients with colonic

vascular ectasias.161 Of the 15 asymptomatic individuals without a history of bleeding, none bled during

a period of follow-up to 68 months (mean, 23 months). For 31 patients with overt bleeding or anemia

who were treated only with blood transfusion, the rebleeding rates at 1 and 3 years were 26% and 46%,

respectively. This study suggests that the risk of bleeding for incidentally discovered lesions is minimal

and empiric therapy is not warranted. However, the risk of recurrent hemorrhage for most symptomatic

patients is substantial and may increase with time.

Medical treatment of vascular ectasias has been used although there is currently no proven effective

medical therapy. Hormone treatment using high-dose estrogens and progesterone has been used since

the 1950s but convincing proof of efficacy is lacking. Indeed, most evidence would suggest no

antibleeding effect of hormonal treatment.164 More recently the antiangiogenic drug thalidomide,

hormones, and octreotide have been suggested as treatment options but data are lacking.165–167

Endoscopic therapy has, however, proved to be more effective. Nonrandomized investigations with

vascular ectasias managed with monopolar electrocoagulation, endoscopic injection sclerotherapy,

contact probes, and lasers have been published with good results. All methods appear to be effective for

treating bleeding vascular ectasias and all are associated with procedure-related morbidity rates of 2%

to 10%. Perforation has been reported in all of these experiences with rates of 2% to 3%.

Patients bleeding from vascular ectasias in whom endoscopic hemostatic methods are unsuccessful or

unavailable can be treated with resection of the colon following preoperative localization of the

bleeding site. For the usual patient bleeding from a vascular ectasia in the cecum or ascending colon, a

right colectomy with ileotransverse colostomy is the treatment of choice. The value of preoperative

localization of the bleeding site cannot be overstated, and every effort should be made to determine the

site of hemorrhage prior to laparotomy.

Ischemic Colitis

Ischemic colitis is a common cause of LGI hemorrhage especially in the elderly. Bleeding is a common

presenting manifestation of ischemic colitis occurring in approximately one-half to three-fourths of

patients but is usually not massive.168,169 Although ischemic colitis may occur with occlusion of a major

artery (such as ligation of the inferior mesenteric artery during abdominal aortic aneurysm repair), in

most cases it results from impaired local microvascular perfusion of the colonic wall. It occurs most

commonly in the elderly who often have significant medical comorbidities. Renal failure requiring

hemodialysis, hypertension, cardiovascular disease, vasoactive medications, and a variety of other risk

factors have been associated with the disease.170 In many cases a specific initiating event cannot be

identified. Any segment of the colon may be involved. Profound ischemia may lead to full-thickness

necrosis, peritonitis, and perforation. Lesser degrees of ischemia may result in vague mild to moderate

abdominal pain (helping differentiate it from diverticulosis), diarrhea, and mild to moderate bleeding.

Life-threatening hemorrhage is uncommon.

Ischemic colitis can be diagnosed with colonoscopy in which case the mucosa may vary from

edematous to hemorrhagic and necrotic. Rarely is angiography helpful in these cases as it rarely

demonstrates major vessel occlusion.169 Most patients will recover uneventfully with supportive care

alone. When operative management is required it is often necessitated by peritonitis or other signs of

full-thickness necrosis. In these critically ill patients the mortality rate is relatively high due to the

critical nature of these patients’ pre-existing comorbid conditions.

UNUSUAL CAUSES OF ACUTE GASTROINTESTINAL HEMORRHAGE

As outlined in Tables 65-1 and 65-2, a wide variety of other pathologic processes may present with

acute GI hemorrhage. Although these lesions generally comprise a relatively small percentage of the

total number of cases of overt GI hemorrhage, they can present vexing problems to the clinician faced

with a bleeding patient in whom the usual etiologies have been excluded. There are a number of case

reports in the literature of extremely rare causes of GI bleeding that will not be discussed here. The

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following lesions occur commonly enough that clinicians are likely to encounter them in their practice.

Dieulafoy Vascular Malformation

Dieulafoy vascular malformation is an unusual cause of recurrent hematemesis, in which bleeding

originates from an unusually large (1- to 3-mm diameter) artery running through the gastric submucosa

for variable distances. Erosion of the gastric mucosa overlying the vessel results in necrosis of the

arterial wall and brisk hemorrhage. The size of the mucosal defect is usually small (2 to 5 mm) and

without evidence of chronic inflammation. These lesions may rarely occur in other anatomic locations of

these lesions such as the colon.171–173

Painless hematemesis and melena are typical. Recurrent bleeding with spontaneous cessation is also

common. In a collective review of 101 cases, the mean age of the patients was 52 years, and the lesion

occurred twice as frequently in men as women. There was no significant association with alcohol abuse

or antecedent symptoms.174

The diagnosis is most frequently made endoscopically by demonstrating arterial bleeding from a

pinpoint mucosal defect. Occasionally, a small arterial vessel may be seen protruding from the gastric

mucosa. Characteristically, the lesions are located within 6 cm of the esophagogastric junction along the

lesser curvature although they may occur in other sites as well.

Most patients can be managed endoscopically by injection of epinephrine, sclerotherapy, banding,

clipping or coagulation.175,176 A subset of patients will require retreatment or surgical excision for

control of hemorrhage. After cessation of hemorrhage few patients rebleed from these lesions even

when treated only be endoscopic methods.177

Gastric Antral Vascular Ectasia

Sometimes abbreviated as GAVE syndrome, this entity is also known as “Watermelon Stomach” because

of its characteristic endoscopic appearance. Longitudinal erosions are seen in the antrum radiating from

the pylorus. It usually causes chronic blood loss and not acute hemorrhage. The etiology is not known

but there is a prominent association with connective tissue disorders. It can usually be treated by

endoscopic argon coagulation but occasionally antrectomy is necessary.178

Angiodysplasia of the Stomach and Small Intestine

Angiodysplastic lesions may occur throughout the GI tract. Similar to colonic lesions, they appear as

minute, flat, or slightly raised red lesions with round or stellate shapes. The margins are

characteristically sharp with a pale mucosal halo surrounding the lesion. The lesions are frequently

multiple and are found most commonly in the stomach and duodenum, although esophageal and small

intestinal involvement has also been described.

In general, these lesions may be diagnosed by endoscopy, although their minute size and sessile

nature may complicate their detection. The lesions may also be readily mistaken for submucosal

hemorrhage associated with acute gastritis or trauma artifact from an NGT or the endoscope. The

lesions may also be demonstrated arteriographically since they have many of the features described for

colonic vascular ectasia.

Endoscopic injections of sclerosants, electrocoagulation, and laser photocoagulation have all been

used to treat gastroduodenal angiodysplasia with good results. The multiplicity of lesions often

necessitates several courses of therapy to eliminate recurring hemorrhage. Surgical resection of the

gastric or intestinal wall containing the lesion as well as oversewing of the bleeding lesion have been

reported to successfully control hemorrhage.

Aortoenteric Fistula

Although communication between the aorta and the intestine may occur as a result of aneurysmal

disease or infectious aortitis (primary aortoenteric fistula), most of those encountered currently are due to

the erosion of an aortic vascular prosthesis through the wall of the distal duodenum (secondary

aortoenteric fistula). The incidence of aortoenteric fistula following aortic reconstructive surgery is about

1% with most of these fistulas arising from the proximal graft anastomosis. Secondary aortoenteric

fistulas are believed to develop after prolonged contact of a prosthetic graft with a fixed segment of

intestine. Ultimately erosion of the graft through the bowel wall results in a low-grade infection around

the graft; involvement of the infection with the suture line leads to dehiscence of the anastomosis and

massive hemorrhage.

The interval between aortic reconstructive surgery and the onset of GI hemorrhage may range from a

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