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COLON
221
roctocolectomy with creation of an ileal pouch–anal anastomo-
P
sis in appropriately selected patients with large bowel Crohn disease
has an acceptable outcome. Most of these patients do as well as persons undergoing the same operation for presumed ulcerative colitis
who were later diagnosed with Crohn disease aer pathologic examination of the resected specimen. Specically, the ileal pouch failure
rate is approximately 15% aer 10 years of follow-up.
SUMMAR
Cr
ohn disease of the colon and ileocolon is initially managed with
Y
medical therapy, but surgery is eventually warranted in many
patients. Patients requiring an elective procedure should be evaluated
with endoscopic and imaging studies and should undergo optimization as dictated by their clinical condition. Whether a laparoscopic
segmental colectomy, total colectomy, or proctocolectomy is performed depends on the patient’s age, operative indication, distribution of disease, severity of disease, and condition of the rectum, anal
canal, and perineum.
u
S
B
Dyson JK, Rutter MD. Colorectal cancer in inammatory bowel disease:
Feagins LA, Holubar SD, Kane SV, Spechler SJ. Current strategies in the man-
Melton GB, Fazio VW, Kiran RP, etal. Long-term outcomes with ileal pouch-
Rosenfeld G, Qian H, Bressler B. e risks of post-operative complications
Tek ki s P P, Purkayastha S, Lanitis S, etal. A comparison of segmental vs subto-
Umanskiy K, Malhotra G, Chase A, et al. Laparoscopic colectomy for
S t
g g e
aumgart DC, Sandborn WJ. Crohn’s disease. Lancet. 2012;380:1590–1605.
what is the real magnitude of the risk? World J Gastroenterol. 2012;18:
3839–3848.
agement of intra-abdominal abscesses in Crohn’s disease. Clin Gastroen-
terol Hepatol. 2011;9:842–850.
anal anastomosis and Crohn’s disease: pouch retention and implications of
delayed diagnosis. Ann Surg. 2008;248:608–616.
following pre-operative iniximab therapy for Crohn’s disease in patients
undergoing abdominal surgery: a systematic review and meta-analysis.
JCrohns Colitis. 2013;7:868–877.
tal/total colectomy for colonic Crohn’s disease: a meta-analysis. Colorectal
Dis. 2006;8:82–90.
Crohn’s colitis. A large prospective comparative study. J Gastrointest Surg.
2010;14:658–663.
e d
R
e
a d i n g
M
P C
D
James M.
ODUCTION
INTR
P
erianal disease is the presenting symptom in 5% of patients with
Crohn disease, but overall up to 80% of patients experience anal
symptoms. An understanding of the pathophysiology of the anal
disease is basic to appropriate management and successful control
of symptoms. e purpose of this chapter is to present a rational
approach to dealing with perianal disease in patients with Crohn
disease.
ATHOPHYSIOLOGY
P
e key to successful treatment of perianal Crohn disease is rec-
ognition of perianal Crohn disease, in which the anoderm and
perineal skin are aected by Crohn disease at a microscopic level.
e Crohn disease–related inammation, including granulomas,
is in the perianal and perineal tissues themselves. When this is
the case, incisions do not heal and local surgery is doomed to fail.
Perineal Crohn disease does respond well to anti–tumor necrosis
factor (TNF)-α therapy, however. Perineal Crohn disease can be
diagnosed clinically by the appearance of the tissues. Waxy perineal
edema, spontaneous ulceration, painless ssures, large edematous
tags, and a split in the skin of the natal cle are characteristic ndings. Figg and Church describe these appearances, some of which
are shown in Figure 44-1. Histologically, granulomas can be found
in most patients. e proportion of patients with these extremely
symptomatic ndings is likely to vary between studies and centers,
accounting for some of the variation in results achieved by surgery
or anti-TNF-α treatment. e presence of perineal Crohn disease
has the following implications:
1. S
urgical incisions will not heal.
2. S
ymptoms will respond to biologic agents.
3. A
er a proctectomy, the perineal wound still may not heal and
biologic agents might still be needed.
Th
e alternative pathophysiology in patients with Crohn disease in whom perianal disease develops is cryptoglandular sepsis,
chronic diarrhea-induced anal stenosis, hemorrhoidal disease,
or the “common” fissure made more common and more severe
by diarrhea related to Crohn disease. Here the perianal skin and
anoderm look normal, and treatment for the manifestations
can be the same as the standard treatment in patients without
Crohn disease. Incisions will heal, but biologic therapy will be
ineffective.
It is obvious that the success rate of biologic agents and surgery in
the management of perianal disease in any series will depend on the
proportion of patients with perineal Crohn disease in any treatment
group. e combination of biologic agents rst and then surgery is
ideal for patients with perineal Crohn disease.
Church
THER CONSIDERATIONS
O
O
ther considerations in the management of perianal Crohn disease
are the small bowel and colon, the rectum, and the anus itself.
If patients have had a functionally signicant amount of bowel
removed, the impact of stooling on the anus is magnied. In this case,
“signicant” means loss of enough bowel to cause chronically more
frequent or more liquid stools.
If the rectum is aected by active Crohn disease, the symptoms of
urgency and tenesmus may be added to stool frequency. In addition,
ulcerations in the low rectum preclude any surgery.
e anus itself can be aected by Crohn disease or by treatments
that others might have performed. Anal stenosis is a common nding
in patients with chronic diarrhea because the constant liquid stools do
not have the dilating eect of normal, formed stools. e anal stenosis
makes access to the anal canal dicult for surgeons and endoscopists. At
the other end of the spectrum, anal laxity—a consequence of ill-advised
surgery, childbirth, or aging—produces incontinence or mucus seepage
that aggravates any symptoms from the Crohn disease itself.
PRESENT
Anal Sepsis
erianal abscess and stula are the most common manifestations of peri-
P
anal disease in patients with Crohn disease. e abscess oen follows an
accelerated course, especially when perineal disease is present. Spontaneous or therapeutic drainage leads to a stula. Crohn stulas are atypical
in that the internal opening(s) can be eccentric and multiple, and tracts
can be complex. Patients with Crohn disease seem to have reduced resistance to spread of sepsis in the perineum, which makes early control of
the sepsis important. Uncontrolled sepsis spreads across the perineum,
creating new external openings and complex cavities.
ags
Anal T
Large “elephant ear” anal tags are diagnostic of Crohn disease and
cause irritation for patients. Because of the possibility of perineal
Crohn disease, they should not be excised. Hemorrhoidal tags also
may be present but generally need no treatment.
es
Fissur
P
ainful anal fissures are generally due to diarrhea and are indicative of underlying anal sphincter hypertonicity. They can be
treated in the same way as most fissures: with nitric oxide donor
ATIONS
222
COLON
223
FIGURE 44-1
neum of a patient with perineal Cr
intments or a sphincterotomy. Painless fissures are a sign of peri-
o
What ha
ppens when an incision is made in the peri
ohn disease.
-
neal Crohn disease and should be left alone.
Stenosis
Anal stenosis in a patient with Crohn disease may be the eect of
chronic diarrhea. In this case there is no point in dilation because the
stenosis will always recur. It is usually not symptomatic because it is
an adaptation to the diarrhea. However, the anus must be dilated to
gain access for procedures involving the anoderm or anal canal.
erianal Skin Irritation
P
Chronic wetness due to discharge or seepage damages the perianal
skin and causes pruritus. Scratching then further damages the skin.
e only way to correct this condition is to minimize physical trauma
and keep the perineum dry.
Internal Hemor
T
reatment of internal hemorrhoids in patients with Crohn disease
rhoidal Prolapse
can be tricky. Diagnosis of perineal Crohn disease is key because it
mandates against any sort of surgery. In the absence of evidence of
perineal or anal Crohn disease, hemorrhoidectomy could be performed. However, removal of the anal cushions can predispose to
seepage. Elastic band treatment is also possible, although the chances
of a normal bowel habit will determine its success.
TMENT OF SEPSIS: ABSCESS
TREA
AND FISTULA
e top priority in a patient with Crohn disease–related anal sepsis
is to control the sepsis, which means providing adequate drainage.
Provision of adequate drainage is almost always accomplished during an examination aer induction of anesthesia. Probing and cutting in an awake patient is usually not helpful, and anesthesia with
a local anesthetic is dicult to achieve in a patient with perianal
sepsis.
S
tep 1: Perform an inspection. Aer induction of anesthesia, with
the patient in the lithotomy position, the anus is inspected,
FIGURE 44-2
with extensiv
olling the sepsis: use of Penrose drains in a patient
Contr
e, Crohn disease–related, perianal sepsis.
which should reveal any abscess or draining external stula
opening. It also should show asymmetry of tissue contours,
which is a sign of deeper sepsis. A bluish coloration of the anus
and the presence of edematous tags suggest perineal Crohn
disease. Waxy edema of the perineal skin and spontaneous ulcerations in the perineum or natal cle conrm this suspicion.
Scars from prior operations also may be present.
Step 2: Perform a digital examination. Digital examination re-
veals the tone and length of the anus and any distortions
or evidence of active disease or prior surgery. Sometimes
subcutaneous fistula tracts can be palpated. The presence of
an anal stenosis becomes obvious. Hard nodules in a patient
with chronic perianal Crohn disease should be biopsied to
exclude malignancy.
Step 3: Perform anoscopy. Anoscopy shows the status of the ano-
derm, the anal transition zone, and the lower rectal mucosa.
Rectal ulcerations mean that advancement ap repair will be
impossible and are an indication for anti-TNF-α treatment to
obtain healing. Large prolapsing hemorrhoids may be seen,
and there may be indications of internal openings feeding an
abscess or stula.
Step 4: Drain the abscess. If the abscess is pointing, the site of
drainage is obvious. If there is a choice, drainage should be
performed as close to the anus as possible. Sometimes the
abscess has created a shallow subcutaneous cavity that can
be unroofed, although if concern about perineal disease exists, one should be conservative. If the abscess leads to a
fistula, drainage will be completed by insertion of a seton
drain. If there is no obvious fistula, a mushroom drain can
be used. Probing of a freshly drained abscess in a patient
with Crohn disease must be performed carefully because
it is possible to create false tracks in the fragile, edematous tissues. Nonetheless, probing should be performed
because insertion of a seton drain is important in controlling the sepsis. In addition, gentle probing in all directions
helps identify extensions. Extensive sepsis requires extensive drainage, often with Penrose drains (Fig. 44-2). These
drains can be changed to vessel loop seton drains in the office in 10 to 14 days (Fig. 44-3).
Step 5: Find the stula. Eective, safe probing of a stula tract is
performed gently and sensitively, with a nger in the anus as
a guide. It is analogous to picking a lock. e probe is encouraged to follow the stula tract in all its convolutions. Sometimes the tract is easy to follow because it is straight and wide;
other times it is dicult to follow, with twists and turns in
multiple planes. Goodsall’s rule does not apply to patients with
Crohn disease, and there is a rare possibility that the external
224
FIGURE 44-3
oom catheter to drain a cavity and a seton drain to control a fistula.
r
pening is being fed by a loop of small bowel or sigmoid co-
o
lon that has perforated against the pelvic oor. Narrow tracts
require thin probes, and tract dilation is a good technique.
Knowing the site of the internal opening allows a probe to be
inserted from within the anus, which can then be encouraged
to meet up with a probe in the stula. If the tract cannot be
identied, one should ensure that the external sepsis is well
drained.
Step 6: Locate openings. Patients with chronic perianal Crohn dis-
ease sometimes have multiple openings. Usually one internal
opening, or maybe two, feeds them all. e internal openings
are key. Seton drains must be used for drainage of these internal openings. Seton drains can also be placed into various
other subcutaneous and perineal sinuses, but they will be able
to be removed later.
Step 7: Administer antibiotics. Ciprooxacin and metronidazole
are mainstays in the management of perianal Crohn disease.
In addition to their antibiotic eect, they have calming eects
on the perianal sepsis. Patients should take these antibiotics
until it is clear that the sepsis is controlled.
Step 8: Manage uncontrolled sepsis. If the perianal sepsis can-
not be controlled by local measures, fecal diversion is necessary, which is usually performed by loop ileostomy. Once
the perianal disease is under control, it can subsequently
be repaired, and there is a chance that the ileostomy can be
reversed.
Step 9: Control proximal disease. It is dicult to control perineal
Crohn sepsis when ileitis or colitis is active and causing pain,
diarrhea, and malnutrition. Pari passu with the treatment of
the anal disease is eective management of the abdominal disease. is treatment could be medical or surgical.
Step 10: Provide denitive treatment. Once the sepsis is con-
trolled, usually a minimum of 2 months aer eective seton/
drain placement, consideration is given to managing the stula. At the initial examination aer induction of anesthesia,
the presence or absence of perineal Crohn disease is determined. If the appearances or the nding of granulomas on
ManageMent of Perianal Cr
e long-term way of controlling sepsis: use of a mush
A mor
ohn Disease
iopsy conrm perineal Crohn disease, patients should be
b
treated with anti-TNF medications for some months prior to
any attempt at repair. If it seems unlikely that perineal Crohn
disease is present, and if the rectal mucosa is normal, an advancement ap repair can be scheduled. If repair is not an
option, long-term seton drainage can provide symptomatic
relief.
O/ANOVAGINAL FISTULA
RECT
novaginal fistula in a patient with Crohn disease is difficult
A
to treat because the symptom of gas and stool per the vagina is
disabling. Fecal diversion is used more often for symptom control, and using seton drains is pointless because the tract is short
and usually not infected. The same principles regarding perineal
Crohn disease apply here, however, and they determine the role
of preoperative anti-TNF therapy. Flap repair is the first choice of
surgery as long as a normal perineum is present. If the perineum
is thin, a sphincteroplasty should be performed at the time of
-
repair.
O
THER MANIFESTATION OF
PERIANAL CROHN DISEASE
ags: Leave them alone. Tags are an indication of perineal
T
Crohn disease, and the wounds caused by their excision
may not heal.
Hemorrhoids: Leave them alone, unless they are very symptomat-
ic. Elastic band ligation is a reasonable option for prolapsing,
bleeding hemorrhoids.
Fissure: Painless fissures are an indication of perineal Crohn
disease. Leave them alone and leave the sphincter alone.
Anti-TNF therapy will heal the fissure. Painful fissures can
be treated in the same manner as any painful fissure (see
Chapter 3).
Stenosis: If the stenosis is due to chronic diarrhea, leave it alone. If
it is due to active sepsis, treat the sepsis. An anus with scarring
due to past surgery should be dilated if it is symptomatic. A
steroid injection into the scar may prolong the time to the next
dilation. Anoplasty in a patient with perineal Crohn disease is
potentially disastrous.
Chronic skin problems: Patients with Crohn disease are prone
to chronic skin problems, including irritation, lichenification, and pruritus because of the seepage and discharge that
is often present. Controlling the discharge and keeping the
skin clean and dry is the best way of helping the condition
settle down.
SUMMAR
atients with Crohn disease who have perianal symptoms may have
P
perineal Crohn disease or may have a basically normal perineum
with anorectal disease superimposed by their inammatory bowel
disease–related stooling abnormalities. is dierentiation is key in
providing the correct treatment in the correct sequence and obtaining the best outcomes. Control of sepsis is paramount. An algorithm
summarizing the decision-making process is provided in Figure 44-4.
Y
COLON
225
EUA ± biopsy, drain sepsis
Sepsis controlled
No Yes
Divert
Perineal Crohn Proximal disease
No Yes No Yes
Drain/repair Anti-TNF Treat
Healed?
No Yes
FIGURE 44-4
disease
An alg
orithm for the management of perianal Crohn
. EUA, Examination under anesthesia.
EUA or definitive
management
S
u
g g e
l-Gazzaz G, Hull T, Church JM. Biological immunomodulators improve the
E
healing rate in surgically treated perianal Crohn’s stulas. Colorectal Dis.
2012;14(10):1217–1223.
Figg RE, Church JM. Perineal Crohn’s disease: an indicator of poor prognosis
and potential proctectomy. Dis Colon Rectum. 2009;52(4):646–650.
Hyder SA, Travis SP, Jewell DP, etal. Fistulating anal Crohn’s disease: re-
sults of combined surgical and iniximab treatment. Dis Colon Rectum.
2006;49(12):1837–1841.
Jarrar A, Church J. Advancement ap repair: a good option for complex ano-
rectal stulas. Dis Colon Rectum. 2011;54(12):1537–1541.
S t
e d
R
e
a d i n g
C
U
P
eter G. Deveaux and Michael H. McCafferty
INTR
ODUCTION
S
olitary ulcer of the cecum was rst described by Cruveilhier in 1832.
e subject of cecal ulcers is confusing and complicated because they
are uncommon and have multiple causes. A variety of terms, including solitary cecal ulcer, acute cecal ulcer, and benign solitary cecal
ulcer, have been used to describe these lesions. Case inclusion varies.
For example, Ong et al, in a recent review of “solitary caecal ulcer
syndrome,” excluded cecal ulcers associated with colon cancer, infectious causes, nonsteroidal antiinammatory drug (NSAID) use, and
inammatory bowel disease, whereas the case report and literature
review of “benign solitary cecal ulcer” by Chi and Hanauer described
a case that was caused by an infectious agent. Perhaps it is more useful to consider cecal ulcers in the context in which they are found,
aer which the potential causes can be considered and treatment
can be tailored. Knowledge of the possible causes is essential to this
approach.
AUSES
C
B
ox 45-1 provides an outline of possible causes of cecal ulceration.
With so many possibilities, cecal ulceration is likely the end point
of several pathologic pathways. A detailed history including current
medications, family history of irritable bowel disease or colon cancer,
immune status, and travel history, correlated with presenting symptoms, may point to a possible cause.
Cecal cancer can be confused with less common causes of cecal
ulcer, such as ulcerated submucosal tumors, mycobacterial or ischemic strictures with ulceration, and drug-induced ulceration. ese
conditions can cause profound inammation with a mass eect so as
to suggest an ulcerated cancer.
In an aging society, drug-related cecal ulcers are common.
NSAIDs can damage the stomach, small bowel, and colon. Colonic
ulceration is predominantly right sided. Possible mechanisms of
injury include reactive oxygen species and Na
tion with resultant increased acidication.
A variety of infections can produce cecal ulcers, especially in
immunocompromised patients who are prone to cytomegalovirus
(CMV)-induced cecal ulcers.
GNOSIS
DIA
ecal ulcers can be identied at the time of colonoscopy or during
C
the evaluation of symptoms (Box 45-2). e former scenario is probably most commonly seen in patients taking NSAIDs. Occult blood
loss or blood loss anemia may also be seen in asymptomatic patients
who take NSAIDs. About 3% of regular NSAID users have colonic
ulcers, which are more common with enteric-coated formulations
and usually are found in the cecum or right colon. Terminal ileal
226
+/H+
change altera-
ex
ulceration also may be present. e cecal ulceration can be solitary
or multiple. Upon colonoscopy, these ulcers are commonly found on
the anterior wall of the cecum or on the antimesenteric border within
2 cm of the ileocecal valve. Signicant edema typically surrounds
these ulcers, which may have the appearance of a simple peptic ulcer.
Biopsy results are nonspecic, but brinous granulation tissue and
lymphocyte and broblast inltration with disruption and thickening of the muscularis mucosae have been described. Microvascular
thrombosis in submucosal vessels due to brin deposition may be
seen. In patients with CMV infection, viral inclusions within endothelial cells and broblasts in the lamina propria are seen.
Some patients with cecal ulcers will present with right lower quadrant (RLQ) pain simulating acute appendicitis. A history of NSAID
use or immunosuppression should at least lead to consideration of the
possibility of a cecal ulcer as a cause of the pain. A strong family history of colon cancer potentially related to Lynch syndrome raises suspicion of a right-sided colon cancer. e usual evaluation of a patient
with RLQ pain includes a complete blood cell count and dierential,
routine chemistries, and imaging studies. Computed tomography
BO
X 45-1:
N
eoplastic
Adenocarcinoma
Ulcerated submucosal tumor
Pharmacologic
Nonsteroidal antiinammatory drugs
Methotrexate
Oral contraceptives
Infectious
Cytomegalovirus
Mycobacteria
Entamoeba histolytica
Campylobacter jejuni
Vasc u la r
Vasculitis
Chronic kidney disease
Cecal diverticulitis
Inammatory bowel disease
Ischemia
Idiopathic
BO
X 45-2:
A
symptomatic
Abdominal pain
Perforation
Bleeding
Causes of Cecal Ulcers
Cecal Ulcer Pr
esentations
can ndings are nonspecic but include cecal wall thickening,
s
inammation (streaky or dirty fat) in the adjacent mesocolon, and
occasionally the appearance of a cecal mass, which suggests cancer.
In the appropriate clinical scenario, appendicitis and Crohn disease
may be considered. A barium or water-soluble enema may similarly
suggest cancer. Cecal ulcers, whether idiopathic or associated with a
known cause, can appear to be ulcerated colon malignancies, and an
ulcerated lipoma can mimic an ulcerated colonic malignancy. Colonoscopy with a biopsy will help settle this dierential, although the
clinical setting will dictate whether a colonoscopy is deemed to be
safe. Nonoperative management and delayed colonoscopy is oen
prudent.
COLON
X 45-3:
BO
akefullmedical
•T
dr
Management of Cecal Ulcer
story,
hi
peciallynonsteroidalantiinammatory
es
ug use, inammatory bowel disease, immunosuppressive drugs,
and cytomegalovirus infection
toolcultures
•S
•E
valuatebleeding,
•C
olonoscopy
•C
ompleteresuscitation
•C
omputedtomographyscan
irondecien
(b
iopsyulceredge)
cy,anemia
• Treatinfectiouscause,iffound
oororno
•Forp
ethods, (rare) cecectomy or right colectomy
m
ntrolofpainorbleedingbynonoperative
co
227
MANA
GEMENT
Cecal ulcers can present with localized perforation or free perforation. Management algorithms used for diverticulitis can be applied.
e patient with diuse peritonitis or extensive free air and uid will
require emergency surgery. For the patient who is neither immunosuppressed nor malnourished and who is hemodynamically stable,
resection with primary anastomosis is preferred. e extent of resection will be dictated by the level of concern that the surgeon has about
the possibility of cancer. e immunosuppressed or profoundly malnourished patient will need a resection with an ileostomy.
Percutaneous drainage coupled with antibiotics, gut rest, and
delayed colonoscopy is a standard approach to the patient who presents with RLQ pain and a pericecal abscess. Usually, the patient with
a small pericecal abscess or contained extraluminal gas can undergo
successful management with antibiotics and gut rest alone, followed
later by a colonoscopy.
Colonoscopy ndings in the setting of recovery aer successful
treatment of an abscess or contained perforation vary and may result
in no clear diagnosis. Discontinuation of potentially causative medications, most notably NSAIDs, is important.
Cecal ulcers can present with acute lower gastrointestinal (GI)
bleeding or occult bleeding and anemia. In acute lower GI bleeding, the evaluation includes a detailed history, ruling out an upper
GI source, and a lower GI evaluation that varies depending on the
magnitude of the bleeding and hemodynamic stability of the patient.
If the patient is stable, colonoscopy will visualize a cecal ulcer and
allow biopsy and control of the bleeding. More massive bleeding can
require angiography for localization. Embolization or selective vasopressin infusion are angiographic options if a bleeding site is found.
e decision for surgery versus angiography is dependent on local
expertise and the patient’s characteristics. For example, bleeding
related to CMV infection in a debilitated and immunosuppressed
patient would be associated with a high operative mortality, thereby
favoring angiography.
Occult bleeding is evaluated by colonoscopy. A cecal ulcer should
be biopsied at the periphery and the base. Biopsy results coupled with
the history will oen suggest the cause. If no evidence of cancer is
demonstrated and a drug-related cause is possible, the potentially
causative drug should be discontinued and follow-up blood work
and colonoscopy in 6 to 8 weeks should be arranged. Patients who
re asymptomatic or have less common symptoms, such as diarrhea
a
or constipation, and have a cecal ulcer at the time of colonoscopy can
undergo similar management.
e nding of a normal appendix coupled with focal thickening
and inammation of the cecum during an operation for a clinical
diagnosis of appendicitis is an occasional scenario for encountering a
cecal ulcer. It may be dicult to dierentiate the real cause from cecal
diverticulitis or cancer. Resection of the diseased bowel cures the
problem and settles the diagnostic confusion. A cecal ulcer is rarely
the presumptive diagnosis.
Box 45-3 outlines diagnostic and management decisions.
CONCLUSION
ecal ulcers are uncommon. e diagnosis is not usually made until a
C
colonoscopy or operation is performed (and then only aer the specimen is opened). True idiopathic, solitary ulcers occur, but they are
usually related to NSAID or other drug use or to infectious causes.
Cecal ulceration and its myriad causes can produce RLQ pain
and perforation, bleeding and anemia, and diarrhea or constipation.
Evaluation of these presentations occasionally reveals the diagnosis
of a cecal ulcer(s). Consideration of the possible causes and the status
of the individual patient directs diagnostic and treatment decisions.
g g e
u
S
tila K, Gler S, Gonen C, et al. Benign solitary cecal ulcer: a condi-
A
tion that mimics plastron appendicitis. Turkish J Trauma Emerg Surg.
2010;16(6):579–581.
Chi KD, Hanauer SB. Benign solitary cecal ulcer: a case report and review of
the literature. Dig Dis Sci. 2003;48(11):2207–2212.
Cruveilhier J. Un beau cas de cicatrisation d’un ulcere de l’intestin gae le cla-
tant d’une douzaine d’armels. Bull Soc Anat. 1895;7:1–2.
Nagar AB. Isolated colonic ulcers: diagnosis and management. Curr Gastroen-
terol Rep. 2007;9:422–428.
Nagaria N, Kansagra A, Ahlawat S. Idiopathic cecal ulcer. J Clin Gastroenterol.
2010;44(10):720.
Shah S, Sangman P, etal. Solitary rectal ulcer. Case report and literature re-
view. Oncol Gastroenterol Hepatol Hosp Rep. 2013;2(2).
S t
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a d i n g
e
P
C D
C
Ja
vier Salgado Pogacnik, Jennifer Holder-Murray, and David S. Medich
INTR
ODUCTION
C
lostridium dicile was originally described as a component of the
normal intestinal ora of newborn infants by Hall and O’Toole in
1935, who also demonstrated that this organism produced a toxin
extremely lethal to mice. However, the “C. dicile era” began in 1974
when Tedesco etal reported high rates of pseudomembranous colitis
in patients exposed to clindamycin at Barnes Hospital in St. Louis,
Mo. Furthermore, this study was the rst to use endoscopy as a diagnostic tool for patients with antibiotic-associated diarrhea.
C. dicile–associated diarrhea (CDAD) is presently the most
common form of nosocomial diarrhea in the United States. According to the Centers for Disease Control and Prevention, the annual
incidence of C. dicile infection (CDI) exceeds 250,000 hospitalized
cases, and the prevalence measured by the National Hospital Discharge Survey is estimated to be 9.4 cases per 1000 discharges with a
mortality rate of 1% to 2.5%. On the basis of current incidence rates,
annual costs for management of CDI range between $800 million and
$3.2 billion in the United States per year. Although CDI primarily is
considered to be a nosocomial infection, recent population and hospital-based studies have reported an epidemiologic shi during the
previous decade, including an increased incidence among outpatient
cohorts as well as hospitalized patients. Furthermore, new studies
discovered that these changes in the epidemiology were connected
with the development of hypervirulent strains of C. dicile, currently
recognized as NAP1/BI/027 strains.
C. dicile, a spore-forming gram-positive bacterium, is a normal component of gastrointestinal ora in up to 3% of healthy adults
and is present in up to 20% of persons who are receiving antibiotic
treatment. In several studies, the period between exposure to C. dif-
cile and the occurrence of CDI has been estimated to be a median
of 2 to 3 days. e primary mode of C. dicile transmission resulting
in disease is person-to-person spread through the fecal-oral route,
principally within inpatient health care facilities. C. dicile spores
are resistant to gastric acidity and are able to evolve into the vegetative form in the small intestine aer ingestion. Colonization of the
colon then occurs aer the normal ora is disrupted by the use of
antibiotics or other predisposing host factors. Once the colonization
is accomplished, the bacteria produces exotoxins and other virulence factors that are toxic to colonic mucosa and initiate local and
systemic inammatory cascades. Clinical presentation ranges from
asymptomatic infection or diarrhea when the injury is limited to the
colonic mucosa to severe fulminant colitis when the consequences of
the toxemia become systemic.
Major risk factors for the development of CDAD are advanced age
(>65 years), prior hospitalization, and use of antibiotics. Certain antibiotics have been associated with nosocomial CDI, such as clindamycin, second- and third-generation cephalosporins (especially
ceriaxone), and uoroquinolones. When subdividing antibiotics
for outpatient cohorts, the use of phenoxymethylpenicillin, dicloxacillin, and penicillins with extended spectra remained statistically
228
nicant in a multivariable model analysis as a risk factor for the
sig
development of CDAD. However, neither the antibiotic dosage
nor the length of administration has been found to correlate with
the development of CDI. Other risk factors associated with CDAD
include admissions to long-term care facilities, immunosuppression,
postoperative state, use of proton pump inhibitors, elemental diets,
inammatory bowel disease, and chemotherapy.
PRESENT
ATION OF CLOSTRIDIUM
DIFFICILE INFECTION
e severity of symptoms of CDI is highly variable, ranging from
diarrhea to life-threatening colitis and systemic toxemia. e severity of the disease is likely determined by host factors in combination
with the virulence of the toxin produced by the infecting strain. Typical features include watery diarrhea, with as many as 15 to 30 bowel
movements per day, and leukocytosis. Many patients report abdominal pain or cramps (30% to 60%) and fever (28%). Some patients do
not present with diarrhea and instead demonstrate an ileus.
e peripheral leukocyte count is usually 10,000 to 20,000 leukocytes/mm
emia is a common feature over time because CDI is a protein-losing
enteropathy, and patients who are already malnourished for other reasons may be at higher risk of contracting CDI. In rare circumstances,
patients experience ileus, toxic megacolon, and colonic perforation.
toms. CDI is conrmed by microbiological evidence of C. dicile
toxin and toxin-producing C. dicile in stools or by colonoscopic or
histopathologic ndings that demonstrate pseudomembranous colitis without another cause. Numerous laboratory tests are currently
available. Testing for C. dicile or its toxins should be performed
only on diarrheal (unformed) stool. Anaerobic culture and bacterial
glutamate dehydrogenase antigen tests detect the presence of both
nontoxigenic and toxigenic strains of C. dicile. Toxigenic culture
and polymerase chain reaction for toxin genes detect only the presence of bacteria capable of making toxin; however, these tests cannot separate active disease from colonization. Enzyme immunoassay
testing for C. dicile toxin A and B is rapid but is less sensitive than
the cell cytotoxin assay, and thus it is considered suboptimal compared with molecular methods for the diagnosis of CDI. Repeat testing during the same episode of diarrhea is of limited value and should
be discouraged.
mark of CDAD. Nonetheless, a considerable number of patients with
CDAD do not demonstrate pseudomembranes, and false-negative
rates quoted in larger series are 10% to 25%. Colonoscopy may be
3
b
ut may approach 50,000 leukocytes/mm
DIA
GNOSIS
e diagnosis of CDI is based on a combination of signs and symp-
Colonoscopy can identify pseudomembranes, which are a hall-
3
. H
ypoalbumin-
enecial for patients in whom the clinical suspicion of CDAD is
b
high, yet laboratory test results continue to be negative. Even though
the sensitivity and specicity of a computed tomography (CT) scan
to identify colonic abnormalities in these patients is 52% to 85% and
48% to 93%, respectively, various studies have suggested that the
early use of CT scanning is highly eective in determining whether
patients have fulminant colitis. Typical CT ndings include severe
colonic wall thickening, dilation, the “accordion sign” (i.e., oral contrast material attenuation in the colonic lumen alternating with an
inamed mucosa with low attenuation), ascites, and pericolonic
stranding.
MEDIC
G
uidelines from the Society for Healthcare Epidemiology of America
AL MANAGEMENT
(SHEA) currently recommend discontinuing therapy with the inciting antibiotic as soon as possible because this may inuence the risk
of CDI recurrence. e treatment of an initial episode of mild to
moderate CDI (dened by the Infectious Disease Society of America
as a white blood cell count [WBC] <15,000 or a serum creatinine level
elevated <1.5 times the baseline) includes metronidazole, 500 mg
orally three times per day for 10 to 14 days. Vancomycin is the drug of
choice for an initial episode of severe CDI (dened as a WBC >15,000
or a serum creatinine level increased 50% over baseline [without
hypotension, shock, or ileus]). e dosage is 125 mg orally four times
per day for 10 to 14 days. For severe complicated CDI, the medical treatment of choice is vancomycin administered orally, 500 mg
four times per day and per rectum as a retention enema (500 mg in
approximately 100 mL normal saline solution, if the patient presents
with an ileus), plus intravenous metronidazole 500 mg every 8 hours.
Surgical consultation should be obtained early in patients with severe
CDI. At the rst recurrence, SHEA recommendations are to repeat
the antibiotic regimen rst used, with recurrences thereaer treated
with vancomycin given in tapered (usually for 7 weeks) or pulsed regimens. Treatment guidelines for severe recurrent refractory CDAD
have not yet been established.
New therapies such as fecal microbiota transplantation (FMT)
have been explored. A systematic review performed by Cammarota etal demonstrated that 467 of 536 patients (87%) experienced
resolution of diarrhea aer FMT. Diarrhea resolution rates varied
according to the site of infusion, with 81% in the stomach, 86% in the
duodenum/jejunum, 93% in the cecum/ascending colon, and 84%
in the distal colon. No severe adverse events were reported with the
procedure. Cammarota etal concluded that FMT is both ecacious
and safe for the treatment of recurrent CDI. e ecacy of new drugs
such as daxomicin (macrocyclic antibiotic) has not been proven in
this setting. Administration of probiotics to prevent primary CDI is
not recommended because data to support this approach are limited
and there is a potential risk of bloodstream infection, specically
S
accharomyces cerevisiae fungemia.
SURGIC
urgical treatment is considered in severe, complicated, or fulmi-
S
AL MANAGEMENT
nant CDI. Although no clearly dened guidelines exist for timing
or indications for surgery, multiple risk factors for increased disease
severity have been identied. ese risk factors include advanced
age, admission for diarrhea, hypotension, coagulopathy, uid or
electrolyte abnormalities, acute renal failure, marked leukocytosis
or leukopenia, hypoalbuminemia, recent abdominal surgery, weight
loss, and history of malignancy. General indications for surgical
management include colonic perforation, multisystem organ failure,
and failure of medical management. Making the decision to intervene surgically aer failure of medical management can be dicult.
Consideration should be given to patients who are elderly and those
with worsening sepsis, cardiopulmonary compromise, or failure of
COLON
BO
X 46-1:
Fulminant Clostridium Difficile Inf
istory of ongoing or recent diarrhea and one of the following:
H
1. P
2. En
3. C
Indications f
or Surgical Management in Severe,
ection
C. d
ositive
icile assay
doscopic ndings of pseudomembranous colitis
omputed tomography scan ndings with colitis
229
And any one of the following criteria:
eritonitis
1. P
2. W
3. S
4. N
5. N
6. M
7. U
8. E
orsening abdominal pain or distention
epsis
ew respiratory failure
ew or increasing vasopressor requirement
ental status changes
nexplained clinical deterioration
vidence of colonic perforation on imaging
9. Nonimproving or worsening white blood cell count >20,000
r <3000 despite appropriate antibiotic therapy for 48-96
o
hours
*M
odied from Neal MD, Alverdy JC, Hall DE, etal. Diverting loop ileostomy and
colonic lavage: an alternative to total abdominal colectomy for the treatment of severe,
complicated Clostridium dicile associated disease. Ann Surg. 2011;254(3):423-427;
discussion 427-429.
leukocytosis to improve aer 48 to 96 hours of appropriate antibiotic
therapy (Box 46-1).
Although CDI resolves with medical management in most patients,
some patients require more aggressive treatment. It is estimated that
approximately 0.4% to 1.9% of cases result in a colectomy. Some evidence shows that in patients with very severe disease, early surgical
intervention improves mortality. erefore, in patients with increased
disease severity and poor prognostic signs, surgical therapy should be
considered early. Surgical options include subtotal or total abdominal
colectomy with end ileostomy or diverting loop ileostomy and colonic
lavage. Both options allow for restoration of intestinal continuity
in the future. Subtotal or total abdominal colectomy is usually performed utilizing an open technique given the severity of illness and
the poor quality of colonic tissue. e colon should be divided at the
distal s igmoid or rectosigmoid junction. e residual rectum can be
ithin the abdominal cavity if a good closure is obtained, sutured
le w
o the inferior portion of the midline abdominal fascial closure, or
t
atured to the abdominal skin as a standard mucous stula. Some
m
surgeons advocate use of rectal lavage with vancomycin irrigation.
Transanal drainage with a Penrose or so rubber catheter may also
help decompress the Hartmann pouch. ese latter methods may help
minimize the risk of rectal stump leak and its complications.
A new alternative to colectomy with end ileostomy has been
described with positive results. Neal etal describes the laparoscopic
creation of a diverting loop ileostomy combined with intraoperative
colonic lavage using 8 L of warm polyethylene glycol solution. is
procedure was performed in all patients who presented with nonperforated fulminant CDI at a single institution over an 18-month
period. Postoperatively, the patients received 10 days of antegrade
vancomycin enemas and IV metronidazole. Mortality was 19%, and
only 3 of 42 patients required a subsequent total abdominal colectomy. is procedure may be a promising surgical alternative to
colectomy in the treatment of severe, fulminant CDI, allowing preservation of the colon. Patients are actively being enrolled in a randomized multicenter clinical trial employing this technique.
Mortality rates aer a colectomy for CDI have varied from 30%
to 57%. Variables associated with increased mortality are listed in
Box 46-2 and reect a disease severe enough to cause multiorgan
failure, supporting earlier surgery, while organ function is still
adequate. Several authors have attempted to devise scoring systems
to delineate CDI severity. One simple validated system includes
four variables: age greater than 70 years (2 points), WBC greater
than 20,000 or less than 2000 (1 point), cardiopulmonary failure
230
X 46-2: Predictors of Mortality
BO
redictors of mortality in fulminant C. dicile colitis
P
dvanced age
1. A
2. W
3. L
4. C
5. R
6. M
P
hite blood cell count >35,000 or <4000
actate >5
ardiopulmonary failure
enal failure
ental status change
redictors of mortality aer surgical management
Pseudomembranous Clostridium diffiCile Colitis
1. Advanced age
ardiopulmonary failure
2. C
cute renal failure
3. A
oagulopathy
4. C
ypoalbuminemia
5. H
eripheral vascular disease
6. P
7. C
ongestive heart failure
8. C
hronic obstructive pulmonary disease
9. M
ental status change
10. Surgery more than 3 days aer admission
equiring mechanical ventilation or vasopressors (7 points), and dif-
r
fuse abdominal tenderness (6 points). A score greater than 6 was
predictive of fulminant disease. e authors suggest careful evaluation and early surgery in this patient cohort.
CONCLUSION
I is increasing worldwide, and hypervirulence is emerging.
CD
Although most patients resolve the CDI with medical therapy alone,
those with severe, fulminant disease have a worse prognosis, and
mortality remains high in this cohort. Surgical treatment should
be performed earlier in the disease course for improved outcomes.
S
urgical options include total abdominal colectomy with end ileostomy or diverting loop ileostomy and intraoperative colonic lavage.
is newer strategy of loop ileostomy with colonic lavage oers
promising results.
S
u
g g e
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ams SD, Mercer DW. Fulminant Clostridium dicile colitis. Curr Opin Crit
Care. 2007;13(4):450–455.
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the treatment of Clostridium dicile infection: a systematic review. J Clin
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S t
e d
e
R
a d i n g