Improved Outcomes in Colon and Rectal Surgery part 36 pps

 improved outcomes in colon and rectal surgery Although 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 treatment 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 disease 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 recommended 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 therapy. 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 having 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 disease.(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 infections, infusion reactions, serum-sickness-like reactions and a possible 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 prognostic variables at the time of surgery: female gender, perianal disease, smoking, use of 5-ASA, jejunal site, ileal and ileocolonic site, and Nod2/Card15 gene variants. Severity of endoscopic recurrence at the neoterminal ileum within 1 year of surgery was found to be the most powerful predictor of symptomatic recurrence.(89)  surgery for crohn's disease Most 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, double-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 treatment 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 postoperative 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 postoperative 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, controlled 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 prevention 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 during 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 complication, 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 steroid-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 indications 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, inflammatory masses or abscesses, or perianal ulcers at any time in the course of disease. Neither postoperative intraabdominal complications 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 Obstruction Inflammatory mass Sepsis Free perforation/sepsis Fistulae/abscess Hemorrhage/anemia Dysplasia/carcinoma Growth retardation  improved outcomes in colon and rectal surgery fissures, perirectal abscesses, and anorectal fistulae. Emergency surgical therapy for a perforation behavior includes: free perforation, intraabdominal abscess or masses with sepsis, and intestinal obstruction. In Crohn’s disease, free perforation is a rare but severe complication 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 procedures. 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 colitis, 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 segment, 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 intraabdominal 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 gastrointestinal tract or colon in about one-third to one-half of patients. It is often associated with colonic and rectal inflammation. Perianal manifestations include cutaneous (tag and ulcerations), 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 treatment 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 recurrent 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 rectal 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 therapy, 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).  surgery for crohn's disease fistula tract. Series using fibrin glue for perianal fistulas of mixed etiologies have yielded success rates of approximately 30–70%.(109) Gracilis transposition can be an option in patients after proctocolectomy 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 medical and surgical 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 considered the best option for gastro-duodenal obstruction strictureplasty has become acceptable.(113) Complete or near-complete intestinal obstruction unresponsive 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 manifestation 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 resection. 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 experience, and prospectively found that the rates of elective surgery 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 status, 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 combination 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) 2 improved outcomes in colon and rectal surgery Stricture biopsy The morbidity rate ranges from 10.2–13%, with fistula formation as the most frequent complication.(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 anastomosis should be between two and of grossly normal bowel. Histologic disease free margins and further resection add no benefit 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 colectomy 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)  surgery for crohn's disease Figure 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) (A) (B) (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 anastomosis site.(135) segmental resection or colectomy with an ileorectal anastomosis has been used. A meta-analysis done in 2005 comparing segmental versus 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 complications, 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  improved outcomes in colon and rectal surgery Reoperation 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 complications do not correlate with recurrence. QUALITY OF LIFE AFTER SURGERY: Patients who undergo surgical treatment for CD experience improvement 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 follow-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 indicated 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. REFERENCES 1. Crohn BB, Ginzburg L, Oppenheimer GD. Regional ileitis. A pathological and Clinical entity. JAMA 1932; 99: 1323–9. 2. Lockhart-Mummery HE, Morson BC. Crohn’s disease (regional enteritis) of the large intestine and its distinction from ulcerative colitis. Gut 1960; 1: 87–105. 3. Vermeire S, Rutgeerts P. Chapter 54: Crohn’s Disease in the … edition of Diseases of the Gut and Liver. 4. Heresbach D, Alexandre JL, Bretagne JF. ABERMAD ((Association Bretonne d’Etude et de Recherche sur les Maladies de l’Appareil Digestif). Crohn’s disease in the over- 60 age group: a population based study. 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Azathioprine and 6-MP have both been used exten- sively in.  improved outcomes in colon and rectal surgery Although TPMT testing is helpful in avoiding early, profound bone marrow suppression, it should not take the place of careful monitoring of

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