Biologic Response Modifiers In 1998, the FDA approved use of Infliximab for use in treatment of moderate to severely active CD and patients with fistulizing Crohn’s disease, who have had
Trang 1Although TPMT testing is helpful in avoiding early, profound
bone marrow suppression, it should not take the place of careful
monitoring of full blood counts throughout the duration of
treat-ment on AZA/6-MP If the patient is a slow metabolizer, clinical
decision on treatment dose with consideration for lower dosing
and closer follow-up must be made, while those that are deficient
should not be treated due to bone marrow toxicity Patients who
are found to be nonresponders are suggested to have metabolite
testing The utility of measuring the 6-MP metabolites 6-TGN
and 6-MMP has been debated in the literature and even referred
to as the “metabolite controversy” According to expert opinion, it
would seem reasonable to recommend checking 6-TGN/6-MMP
metabolites when patients are not achieving therapeutic efficacy
despite adequate weight-based dosing to ascertain noncompliance
or metabolism favoring 6-MMP.(59)
Methotrexate has also been shown to be effective in CD for
both treating active disease (66) and maintaining remission (67)
However, like AZA/6-MP, its slow onset of action limits its use in
induction therapy Nausea is a common side effect of methotrexate,
but more serious concerns over opportunistic infections,
hypersen-sitivity pneumonitis, and hepatotoxicity add to the factors limiting
its use as a first line immunomodulator in treatment of CD
Although some data have suggested a beneficial effect of
high-dose cyclosporine in active luminal CD (68), the benefit was not
durable (69) An open-label trial of 16 patients with fistulizing
dis-ease found that cyclosporine treatment resulted in 88% response
and 44% complete closure.(70) However, a comprehensive review
of the literature has shown that 39 patients with fistulizing disease
who were treated with cyclosporine had 82% relapse rate in absence
of oral cyclosporine.(71) Therefore, cyclosporine is not
recom-mended for use in luminal CD and its use in fistulizing disease
with subsequent maintenance therapy on AZA/6-MP is debatable
(72) Cyclosporine has several serious side effects including renal
failure, seizures, and opportunistic infections
Biologic Response Modifiers
In 1998, the FDA approved use of Infliximab for use in treatment of
moderate to severely active CD and patients with fistulizing Crohn’s
disease, who have had inadequate response to conventional
ther-apy In fact, it is the first drug to gain FDA approval for treatment
of CD Prior to the late 1990s, patients who had failed response to
first-line therapies or were steroid-dependent had few nonsurgical
options The mechanism of action of biologic response modifiers
in CD is through the interaction of the interleukins and cytokines
Neutrophils from patients with colitis (e.g., CD, ulcerative colitis,
and infectious colitis) all produce significantly more IL-1 and TNF
than neutrophils from healthy controls.(73)
Infliximab is a chimeric IgG-1 monoclonal antibody
com-prised of 75% human and 25% murine sequences, which has a
high specificity for and affinity to tumor necrosis factor (TNF)-α
The pivotal trial for assessing the efficacy of Infliximab in CD in
1997 showed 33% rate of remission and 81% overall symptom
improvement in patients who had been resistant to conventional
treatment.(74) However, up to 40% of patients do not respond
to treatment initially The standard dose of Infliximab at 5 mg/
kg of body weight given as infusion every 8 weeks can sustain
remission for up to 1 year in only 30% of initial responders This
is likely due to a combination of loss of efficacy and intolerable side effects Infliximab also has modest steroid-sparing efficacy where at week 54, about 3 times as many patients (29% vs 9%)
on Infliximab versus placebo had discontinued treatment with corticosteroids while maintaining clinical remission.(75)
The efficacy of regularly scheduled treatment versus episodic treatment with Infliximab for patients with CD was compared
in a posthoc analysis of the ACCENT I trial in 2004.(76) It was shown that regularly scheduled treatment resulted in a higher proportion of patients in remission at weeks 10, 14, 22, and 46 compared with the episodic treatment group Patients were also found to have improved mucosal healing, less likelihood of hav-ing antibodies to Infliximab, fewer Crohn’s-related hospitaliza-tions, and fewer surgeries if on regularly scheduled treatment Infliximab therapy causes antibody formation in up to 61%
of patients and they correlate with increased risk of transfusion reactions as well as decline in efficacy.(77) Concomitant use
of AZA/6-MP has been shown to reduce rate of antibodies to Infliximab (ATI), although currently there is no prospective trial comparing remission and response rates in patients concomi-tantly using AZA/6-MP and Infliximab.(78–80)
Infliximab is also effective in closure of perianal enterocutane-ous and rectovaginal fistulas and maintaining fistula closure Two prospective, randomized, placebo-controlled trials have shown closure rate of 55% at week 4 and maintenance of closure in 39%
of patients respectively.(81, 82)
In February 2007, Adalimumab gained FDA approval for the treatment of moderate to severe CD Adalimumab is a fully human recombinant immunoglobulin G1 (IgG1) monoclonal antibody that binds with high affinity and specificity to human soluble TNF Its efficacy is similar to Infliximab except that there is currently not enough evidence to comment on its value in fistulizing dis-ease.(83) However, certain features make it more attractive for use in clinical practice It is thought that Adalimumab may be less immunogenic because it is a fully human antibody Indeed, some evidence does exist for inducing remission in those who cannot tolerate Infliximab or have disease activity despite receiv-ing Infliximab therapy.(84) Another advantage is that it is admin-istered as a subcutaneous injection whereas Infliximab must be given as an infusion
Main side effects of Infliximab and Adalimumab include infec-tions, infusion reacinfec-tions, serum-sickness-like reactions and a pos-sible increased risk of lymphoma A tuberculin skin test should be done before initiating therapy, as reactivation of latent tuberculosis
is a potential complication
Prevention of Postoperative Recurrence
Approximately 75% of patients with CD require surgery within the first 20 years after symptom onset.(85, 86) Several studies have shown that, 1-year postresection, the endoscopic recurrence rate
is near 73% with clinical relapse rate of 50% in 5 years.(87, 88) Increased risk of recurrence is associated with the following prog-nostic variables at the time of surgery: female gender, perianal dis-ease, smoking, use of 5-ASA, jejunal site, ileal and ileocolonic site, and Nod2/Card15 gene variants Severity of endoscopic recur-rence at the neoterminal ileum within 1 year of surgery was found
to be the most powerful predictor of symptomatic recurrence.(89)
Trang 2Most studies of postoperative recurrence of CD have found that
endoscopic findings predate clinical relapse
Management options to prevent postoperative recurrence vary
and depend on the patient The first line treatment, despite
mar-ginal efficacy, has been mesalamine Most studies only
demon-strate a modest relative risk reduction in recurrence rates when
compared to placebo A recent meta-analysis showed an
abso-lute risk reduction of 10% in postoperative patients at 2 years
(90) The largest benefit was found in pts with ileitis and
pro-longed disease duration The number needed to treat (NNT) to
prevent one relapse was found to be 10 patients.(91) Whether or
not this is a clinically relevant finding and the financial cost and
effort spent in taking these medications merit their use is highly
debatable Azathioprine and 6-MP have both been used
exten-sively in the postoperative patient, but data is limited and shows
only modest efficacy for prevention of recurrence The general
consensus is that larger blinded controlled trials are warranted
A randomized, prospective, multicenter, placebo-controlled,
dou-ble-blind, double-dummy trial done in 2004 by Hanauer showed
relapse rates of 50% with 6-MP (50 mg), 58% with mesalamine
(3 g), and 77% with placebo.(92) There were several shortcomings
in this study, including the use of a suboptimal fixed dose of 6-MP,
a high drop-out rate, higher clinical vs endoscopic relapse rate, and
lack of a validated, reproducible clinical index used to judge clinical
relapse A prospective, open-label, randomized study of 142 patients
who received AZA (2 mg/kg/day) or mesalamine (3 g/day) for
24 months found AZA effective in preventing relapse in those patients
who had undergone previous intestinal resection.(93) Shortcomings
of this study included open label bias Currently, AZA/6-MP use is
recommended for postoperative prophylaxis in those patients who
are deemed to have high risk of recurrence or in those for whom
recurrence would have substantially harmful effects
The use of antibiotics has been long debated in the prevention of
recurrence in the postoperative Crohn’s patient There are no large
controlled trials that show clear effectiveness of the use of antibiotics
in postoperative Crohn’s patients beyond 1 year One large trial on
metronidazole has shown a 4% clinical recurrence rate in the
treat-ment group versus 25% in placebo group at 1 year, 52% endoscopic
recurrence versus 75% in the placebo group at 3 months, and no
significant difference in clinical recurrence rate at 2 or 3 years.(94)
Another trial of Ornidazole showed an 8% clinical recurrence versus
38% with placebo at 1 year, but no significant difference at 2 or
3 years.(95) These agents may be considered for prevention of
post-operative recurrence but their utility beyond 1 year and potential for
considerable side effects in long- term use limit their clinical utility
The last group that has shown possible effectiveness in
post-operative Crohn’s patients is the biologic response modifiers, but
these have yet to be adequately studied in this setting A
nonran-domized, open-label, single-center experience involving 7 patients
who received Infliximab with methotrexate has demonstrated no
endoscopic or clinical recurrence at 2 years.(96) Adalimumab has
not been studied in this respect Multicenter, randomized,
con-trolled studies are needed to further define the role of Anti-TNF
agents in postoperative recurrence of CD
Treatments that have been shown to be ineffective in the
pre-vention of postoperative recurrence are systemic corticosteroids,
budesonide, probiotics, and interleukin-10
Nutritional Therapy
There is no proof that any food or substance is responsible for causing the initial episode or recurrence of CD.(97) The biggest challenge in patients with CD is restoration and maintenance of weight, particularly in the presence of sepsis and/or obstruction
SurgICal trEatMEnt Indication
Table 32.2 summarizes the indications for surgical treatment of
a CD.(98) Surgical management of CD has changed considerably dur-ing the past as a result of numerous advances in medical therapy Regardless of these developments, patients with CD will undergo
a surgical procedure in up to 80% of the cases.(99) Patients often come to the surgeons office with worsening symptoms, a compli-cation, or as steroid-dependent
Failure of medical therapy or complications of medical therapy
• Surgery may be indicated if the medication cannot control inflammation and its symptoms, or if the medication causes significant intolerable or inducible side effects Symptoms that can be an indication for surgery includes diarrhea, anemia, pain, weight loss, sepsis, and obstruction Most patients are either ste-roid-dependent or steroid-resistent (100) by the time of surgical consultation In addition, pancreatitis from GRMP, osteoporosis from steroids, and leucopenia from infliximab are all potential reasons for surgery to be recommended
Acute and chronic disease complications
• Although rates are decreasing, up to 20% of procedures are still performed to treat acute complications.(101) Among the indica-tions is toxic megacolon, obstruction, hemorrhage, perforation with or without peritonitis, and abscess
Perforation
According to the Viena classification, intestinal perforation is a penetrating disease The penetrating disease behavior is defined
by the occurrence of intraabdominal or perianal fistulas, inflam-matory masses or abscesses, or perianal ulcers at any time in the course of disease Neither postoperative intraabdominal compli-cations nor perianal skintags constitute evidence of penetrating disease.(102) Penetration of the bowel wall often presents not as
an acute abdomen but as an indolent process related to fistuliza-tion Diffuse peritonitis due to perforation is a rare but recognized complication of Crohn’s disease Perianal disease manifestations include perianal pain and drainage from large skin tags, anal
Table 32.2 Indications for Surgery in Crohn’s Disease.
Failure of medical management Complications of Medical Management
Dysplasia/carcinoma Growth retardation
Trang 3fissures, perirectal abscesses, and anorectal fistulae Emergency
surgical therapy for a perforation behavior includes: free
perfora-tion, intraabdominal abscess or masses with sepsis, and intestinal
obstruction
In Crohn’s disease, free perforation is a rare but severe
com-plication occurring in 1% to 3% of cases.(103) Free perforation
in the absence of a megacolon should alert for the suspicion of
CD It can occur anywhere in the gastro-intestinal tract, from
the stomach through the colon; a distal stricture might exist and
make the perforation possible Other etiologies for perforation
include the presence of malignancy, and of endoscopic
proce-dures Frequently, the perforations are sealed Gastro-duodenum
perforations are best treated by debridement and primary suture
For jejuno-ileal perforations, resection and primary anastomosis
are best if feasible and conditions favorable Factors associated
with postoperative complications include abscess,
enterocutane-ous fistulae, steroid-dependence, and albumin <2 g/L If one or
more of the risk factors is present, a diversion is suggested.(104)
Colonic perforation in Crohn’s colitis, often seen in the setting
of toxic colitis, usually requires subtotal colectomy with rectal
preservation and end ileostomy If the etiology is not toxic
coli-tis, a segmental resection and fecal diversion might be an option
(105) A postcolonoscopic perforation must be managed
regard-ing the absence or presence of CD at the site of perforation and
elsewhere in the colon If the perforation occurs in a diseased
seg-ment, the segment along with the perforation is reseated to allow
reconstruction with or without fecal diversion depending upon
the factors mentioned above.(104) If perforation occurs during
a follow-up for surveillance, resection or primary repair may be
feasible
Abscess
Between 10–30% of patients with CD may present with
intraab-dominal abscesses Abscesses can develop because of a local
sealed perforation, in association with a fistula, or postoperatively
because of intraabdominal contamination or anastomotic leakage
Yamaguchi et al found that almost 50% of the abscess were due
to an anastomosis (surgical anastomosis and peristomal) (106),
Preoperative percutaneous transcutaneous drainage and
admin-istration of antibiotics is preferable if possible Otherwise, surgery
with resection of the disease site is necessary
Perianal CD
Perianal Crohn’s Disease (PCD) occurs in 5–25% of CD patients
and can be associated with active disease in the proximal
gas-trointestinal tract or colon in about one-third to one-half of
patients It is often associated with colonic and rectal
inflamma-tion Perianal manifestations include cutaneous (tag and
ulcer-ations), anal canal lesions (fissures, ulcers, stenosis), and septic
(abscess, fistulas) (Figure 32.3)
The purpose of surgical treatment in PCD is to improve quality
of life and offer effective palliation, and therefore is reserved for
patients who develop perianal complications of the disease or are
unresponsive to aggressive medical therapy The surgical
treat-ment of PCD can be divided into two main categories: urgent and
emergent treatment (to control perineal sepsis); and elective (to
treat sequelae such as perianal fistulas and anal strictures).(107)
Prompt and definitive surgical incision and drainage is required in all patients suspected of having acute abscesses These lesions will not spontaneously resolve and delays can lead
to uncontrolled sepsis with necrotizing infections, sphincter impairment and anal stenosis If a fistula is identified a noncut-ting Seton (nonabsorbable suture) is inserted through the fistula tract to ensure continuous drainage, leading to the resolution
of the perianal sepsis Primary fistulotomy should be avoided Premature removal of the seton increases the incidence of recur-rent perianal sepsis If the abscess is superficial, the procedure may be completed under anesthesia It is important to mini-mize trauma or additional injuries so that the incision must be
as close as possible to the anal verge Excision of skin edge or latex mushroom catheter placement can be utilized to obtain adequate drainage
Fistulotomy can be safely performed on simple (low) fistulas which do not include any significant portion of the external anal sphincter, in patients without active proctitis, well-controlled proximal luminal disease and adequate continence
Endorectal advancement flap is a surgical technique that repairs perineal fistulas with the preservation of anal sphincter function The principal idea of this procedure is to surgically close the internal opening of the fistula using a flap made of rec-tal wall, allowing the healing of the fistula from inside out The reported success rate of endorectal advancement flap in patients with Crohn’s perianal fistulas ranges from 25 to 100% in different series, with an average success of approximately 50–60%.(108) Elective surgery for PCD may include procedures for nonfistulous complications such as dilation of anorectal strictures Most com-monly, however, patients with PCD will require surgery to repair perianal and rectovaginal fistulas not responsive to medical ther-apy, which may include fistulotomy, fibrin glue injection, transanal endorectal flap advancement, and gracilis muscle interposition Fibrin Glue is a technically simple procedure for the treatment of perianal fistulas and it is associated with low risk and early return
to normal activity Fibrin glue is a blood by-product that uses the activation of thrombin to form a fibrinclot, mechanically sealing the
Figure 32.3 Typical perianal Crohn’s Disease with associated fistulas and scars from
prior surgery (Picture taken by Badma Bashankaev, M.D., Cleveland Clinic Florida).
Trang 4fistula tract Series using fibrin glue for perianal fistulas of mixed
eti-ologies have yielded success rates of approximately 30–70%.(109)
Gracilis transposition can be an option in patients after
proc-tocolectomy or others types of CD related fistulas in whom other
options may have failed before proctocolectomy.(110) Occasionally,
temporary diverting colostomy or ileostomy is required to control
symptoms, and in extremely severe cases resistant to both
medi-cal and surgimedi-cal therapy, proctectomy or proctocolectomy may be
required
The PCD score developed by Wexner et al can be very helpful
in selecting therapeutic alternatives and in prognostication.(111)
The PCD Activity Index analyzes 6 features in PCD: abscess,
fistula, fissure and/or ulcer, stenosis, and incontinence
Obstruction
Gastrointestinal obstruction usually results from acute active
inflammation superimposed on a stenotic segment Mass effect
from an adjacent phlegmon or abscess is not an uncommon
sce-nario Malignancy must be excluded in CD strictures involving the
colon Yamazaki et al noted a 6.8% malignancy rate in 132 patients
with colonic Crohn’s disease complicated by stricture.(112)
Although traditionally by-pass without vagotomy was
consid-ered the best option for gastro-duodenal obstruction
stricture-plasty has become acceptable.(113)
Complete or near-complete intestinal obstruction
unrespon-sive to medical therapy requires surgical correction Depending on
location, this treatment involves either resection or strictureplasty
(114) If malignancy is present or suspected, a resection is obviously
indicated following standard oncologic principles
Bleeding
Whereas mild gastrointestinal bleeding is a common
manifes-tation of inflammatory bowel disease, severe bleeding is a rare
phenomenon CD has been reported to be an established source
of gastrointestinal hemorrhage, in 0.9% to 2.5% of patients with
this disease.(115) CD bleeding is often from a localized source
This is caused by erosion of a blood vessel within multiple deep
ulcerations that extend into bowel wall The small bowel is the
site of bleeding in 65% of cases, whereas the colon was involved
in 12%, and in 23% the site could not be identified
It is important to exclude a gastroduodenal source before bowel
resection Angiography is often performed to identify and possibly
treat the bleeding site by selective or superselective angiographic
infusion of vasopressin.(116) Embolization should be the initial
treatment of choice in CD in an attempt to avoid surgical
resec-tion Cirocco et al (115) reported that surgical resection offered
excellent palliation, with low mortality (3%) and a low
rebleed-ing rate (3.5%) Surgery is indicated in those patients who fail to
show improvement of bleeding after 4 to 6 units of blood, have
recurrent hemorrhage, or have other indications to resect diseased
bowel.(114) A bowel preparation is contraindicated, and the aim
is to remove the patient from life threatening hemorrhage
Toxic Megacolon
Toxic megacolon is a potentially lethal complication which has
gradually decreased in incidence because of earlier recognition
and intensive management of severe colitis A possible mechanism
is that mucosal inflammation sequentially leads to the release of inflammatory mediators and bacterial products, increased nitric oxide syntheses, generation of excessive nitric oxide, and colonic dilation Toxic megacolon affects all ages and both genders Signs and symptoms of acute colitis that are frequently resistant to therapy are often present for at least 1 week before the onset of acute dilatation Severe bloody diarrhea is the most common pre-senting symptom, while improvement of diarrhea usually occurs because of the onset of megacolon Other futures include malaise and abdominal pain and distention.(117) Up to 47% of patients require surgery due to failure in medical therapy Factors affecting mortality are age (>40), gender (female), and presence of colonic perforation The overall mortality rate is 16%.(118)
Although the frequencies of performed emergency surgery have decreased, improved medical treatment has lead to higher rates of elective operations Siassi et al published a 33 years expe-rience, and prospectively found that the rates of elective sur-gery rose from 69.5% (1970 to 1980) to 81.4% (1981–1991) and 80.9% (1992–2002) (101) This change might reflect the changes
in disease location Combined large/small bowel resections such
as ileocecal resections increased from 27.5% (1970–1980) to 41.9% (1981–1991) and 67.1% (1992–2002) (101), as CD limited
to this region that is unresponsive to medical management is best treated by ileocolectomy and anastomosis (119) Similar results were found by Reissman et al with a 59% rate of ileocolectomy and anastomosis.(120)
SpECIFIC ConSIdEratIonS In SurgICal tEChnIquES For Cd patIEnt
The philosophy behind surgical intervention in Crohn’s disease rests on the fact that Crohn’s disease is currently incurable and potentially involves the entire intestine, and that surgery relieve only the complications
Strictureplasty
Over one-third of patients with CD will develop an intestinal stricture and the great majority of these will require at least one surgical procedure The initial view was that strictureplasty should only be undertaken for recurrent disease and in patients who have had previous multiple resections The potential benefits
of any surgery include symptom relief, improved nutritional sta-tus, and reduced dependence on medication The most obvious advantage of strictureplasty over resection is that the development
of short bowel syndrome can be avoided All jejunoileal strictures and most duodenal strictures are able to strictureplasty.(121) The procedure can also be undertaken in patients with symptomatic anastomotic strictures Table 32.3 shows current indications for strictureplasty and contraindications.(122)
There are two main types of operation used The Heineke– Mikulicz procedure is used for strictures of up to 10 cm in length For strictures up to 25 cm long, the Finney procedure (a side to side amastomosis) is done Most of the others methods of strictureplasty are generally derivations of one of the above methods, or a combi-nation of both In 2000, Tichansky et al published a meta-analysis that showed that Heineke-Mikulicz technique is most often used for Crohn’s strictureplasty However, the outcome revealed that the Finney strictureplasty may reduce the reoperation rate.(123)
Trang 5Stricture biopsy
The morbidity rate ranges from 10.2–13%, with fistula
forma-tion as the most frequent complicaforma-tion.(123) Strictureplasty has
been found to be a safe and efficacious procedure for small bowel
Crohn’s disease.(124)
Resection
The most common surgery is ileocolic resection (Figure 32.4a,
32.4b, 32.4c), usually undertaken for medical therapy failure, fistula,
obstruction, mass, perforation, or malignancy The development of
malignancy increased to 4 to 20 times of the average population
As previously mentioned, strictureplasty site should be evaluated
for intraoperative biopsy and resection, the only procedure which
should be considered in the setting of carcinoma Over the past two
decades, laparoscopic resection has demonstrated clear superiority
over laparotomy relative to postoperative recovery, cost, morbidity,
cosmesis, and long-term bowel obstruction.(125–128)
Regardless of the technique of resection performed, the
anas-tomosis should be between two and of grossly normal bowel
Histologic disease free margins and further resection add no
ben-efit and may predispose to the onset of short bowel syndrome
Bemelman et al (129) showed that medical therapy was able
to prevent surgery in one third of the cases of CD in the terminal
ileum Patients who probably will fail medical therapy are those
with stenosis, extraintestinal manifestation, or known history of CD
for more than 5 years Some patients might undergo resection if the
obstruction is contra-indicated to have strictureplasty Many studies
compare the outcomes between medical therapy and conventional
laparoscopic procedure A meta-analysis done in 2007 showed
14 studies with 881 patients The operative time for laparoscopic
surgery was longer, but morbidity was lower.(130)
The Surgical treatment for large bowel Crohn’s disease has
included total proctocolectomy, segmental colectomy or
colec-tomy with ileorectal anastomosis (IRA), depending on severity and
disease distribution Conventional proctocolectomy is reserved
for those patients with anorectal involvement, but in the 50%
of patients with large bowel Crohn’s disease with rectal sparing,
Table 32.3 Current indication for strictureplasty and
contraindications
Indication
Previous extensive (>100 cm) resections of small bowel
Short bowel syndrome
Duodenal strictures
Rapid recurrence of disease with obstruction
Strictures at previous anastomotic sites, particularly ileorectal or ileocolic
Fibrotic strictures within diffuse involvement of the small bowel
Small bowel stricture (active or nonactive disease)
Contra indications
Perforation of the small bowel, with or without peritonitis
Serum albumin <2.0 g dl
Fistula or phlegmonous inflammation at intended strictureplasty site
Likelihood of tension on closure of strictureplasty
Intended strictureplasty site next to segment requiring resection
Presence of malignancy
Figure 32.4 (A)Terminal ileal strictures are the most common cause for surgery
(Picture taken by Wang Hao, M.D., Cleveland Clinic Florida) (B) The best surgical option for stricturing terminal ileal disease is often an ileocolic resection (Picture taken by Wang Hao, M.D., Cleveland Clinic Florida) (C) The length
of the narrowing in the small bowel varies (Picture taken by Wang Hao, M.D., Cleveland Clinic Florida)
(A)
(B)
(C)
Trang 6Figure 32.5 (A) After an ileocolic resection, the recurrence is most commoly at the anastomotic site (arrow) (Picture taken by Jorge Canedo, M.D., Cleveland Clinic
Florida) (B) A 15 cm stricture; also note the creeping fat (Picture taken by Jorge Canedo, M.D., Cleveland Clinic Florida) (C) Small bowel resection and anastomosis (Picture taken by Jorge Canedo, M.D., Cleveland Clinic Florida) (D) Note the thick fibrotic stricture (Picture taken by Jorge Canedo, M.D., Cleveland Clinic Florida)
(D) (C)
resection diminishes over time, especially from more than 20 years after the first resection.(133)
Bypass
Bypass surgery enjoyed popularity many decades ago, at the begin-ning of CD surgery, when complication rates for resection were high However, it fell out of use due to high rates of recurrence, great metabolic changes, higher risk of malignancy, and higher rates of postoperative complications.(104)
Bypass surgery is currently undertaken for duodenal stricture, although fecal diversion may have a long dysfunctional segment Diversion without resection may be indicated in very selective situations, like severe perianal disease.(134)
poStopEratIvE rECurrEnCE aFtEr SurgEry
Rates for recurrence after resection are up to 73% after 1 year, although only 20% of patients have symptoms After 3 years, recurrence has been noted in 85% of patients, with symptoms present in only 34% The site of recurrence is usually the anasto-mosis site.(135)
segmental resection or colectomy with an ileorectal anastomosis has
been used A meta-analysis done in 2005 comparing segmental
ver-sus subtotal ⁄ total colectomy concluded that both procedures were
equally effective as treatment options for colonic Crohn’s disease,
however, patients in the SC group exhibited recurrence earlier than
those in the IRA group.(131) The choice of operation is dependent
on the extent of colonic disease Better outcomes are expected for
IRA in patients with two or more colonic segments involved
A meta-analysis done in 2007 compared the end-to-end
anas-tomisis to other configurations (132) and found that end-to-end
anastomosis after resection for Crohn’s disease may be associated
with increased anastomotic leak rates Side-to-side anastomosis
may lead to fewer anastomotic leaks and overall postoperative
com-plications, a shorter hospital stay, and a perianastomotic recurrence
rate comparable to end-to-end anastomosis Further randomized,
controlled trials should be performed for confirmation
Resection is contra-indicated in duodenum stricture, due the
high risk of the procedure In order to avoid short small bowel
syndrome, the resection should include macroscopic intestinal
disease It is known that activity of CD necessitating intestinal
Trang 7Reoperation for recurrence rates after strictureplasty is between
24–26% after 5 years Medical therapy may have a great value in
lowering rates of recurrence Smoking significantly increases the
risk of recurrence after surgery for CD, especially in women, and
it is dose-dependent Another feature that influences recurrence
after surgery is a short duration of disease before surgery
The site of the disease also affects recurrence rates, as small bowel
and ileocolic disease have higher rates of recurrence (Figure 32.5a,
32.5b, 32.5c, 32.5d) Perforation is associated with a higher rate
of recurrence in patients who have had a colonic resection.(136)
Gender, family history of CD, blood transfusion, length of resection,
presence of granuloma in the specimen, and postoperative
compli-cations do not correlate with recurrence
qualIty oF lIFE aFtEr SurgEry:
Patients who undergo surgical treatment for CD experience
improve-ment in Health-related Quality of Life (HRQL) up to 1 year after
surgery Most of the studies focus on assessment of quality of life for
ileocolic resection, the most common procedure Controversies exist
as to whether there is actually improvement or not in a long term
fol-low-up for these patients Thaler et al (137) concluded that HRQL
actually reduces in patients with CD in a long-term follow-up, no
matter whether the surgery was open or laparoscopic compared to a
normal control population And recurrence was the most important
factor adversely affecting quality of life
Casellas et al (138) analyzed the impact of previous surgery
for complicated or refractory CD on HRQOL The results
indi-cated that patients with active CD have a serious impairment in
HRQOL and patients with a history of previous surgical bowel
resection are not different from patients who have never had
surgery, as long as those patients remain in clinical remission
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