Overview of Surgical Therapy for Crohn’s Disease





List of Abbreviations


APR


Abdominoperineal resection


CD


Crohn’s disease


CDAI


The Crohn’s Disease Activity Index


CTE


Computed tomography enterography


FDA


Food and Drug Administration


HM


Heineke–Mikulicz


LIFT


Ligation of the intersphincteric fistula tract


MRE


Magnetic resonance enterography


SSIS


Side-to-side isoperistaltic strictureplasty


TNF


Tumor necrosis factor


TPN


Total parenteral nutrition




Introduction


Crohn’s disease (CD) is a chronic inflammatory disease of the intestinal tract with an unknown etiology or cure. The characteristic transmural inflammation can progress to refractory inflammatory disease, stricturing disease, and fistulizing disease—all potential indications for surgery when medical management has been exhausted. An important tenant to remember is that surgery is not curative but is rather an adjunct to maximal medical therapy. Thus, a mindset of symptom control and bowel preservation is imperative as up to two-thirds of the patients will require subsequent operations in their lifetime.




Medical Treatment of Crohn’s Disease


Because there is no known cure for CD, the goal of medical management is symptom control and, ideally, maintenance of disease remission. With a vast number of medications now approved for the treatment of CD, medical management is largely dictated by severity and phenotype of disease. For the treatment of mild disease, patients are often treated with 5-aminosalicylate products such as sulfasalazine, oral mesalamine (Pentasa, Asacol), or rectal mesalamine. For moderate to severe disease, corticosteroids were historically the cornerstone of medical management. However, with the US Food and Drug Administration (FDA) approval of infliximab in 1998 for the treatment of CD, we have entered an age where biologic therapy is supplanting many other therapies. Initially, biologic agents were only given to patients with severe disease, half of whom had already required surgery for complications, and a third of whom had failed to respond to thiopurines. However, post hoc analysis of the large randomized controlled trials found that overall remission rates with biologics were greater when administered to patients within 2 years of diagnosis. Thus, biologics are now being introduced to patients with moderate to severe active disease, prior to the development of strictures, whom are at a higher risk of complications. Unfortunately, up to 60% of patients experience recurrence of symptoms after induced remission with antitumor necrosis factor (TNF)α agents. In the past, most of these patients would have gone to the operating room. Now, rather than going to surgery, an alternative anti-TNFα agent (e.g., adalimumab or certolizumab pegol) or class of biologic therapy, including vedolizumab (binds integrin α4β7) or ustekinumab (binds to IL-12 and 23) is being administered. Therefore, patients are arriving to the operating room later, with more advanced disease, increasingly malnourished and immunosuppressed—arguable, a sicker patient population than before the introduction of biologic therapy.


This underscores the importance of a multidisciplinary approach to the management of these challenging, and often, medically refractory patients. The patient, gastroenterologist, and surgeon should all be in close communication as the patient’s disease severity increases and surgery becomes increasingly likely. Prior to exhausting all medical options, a patient should have at least undergone a surgical consultation to understand the risks and benefits of an operation versus ongoing medical management. Ideally, consensus will be reached by all involved parties prior to the patient being taken to the operating room.




Indications for Surgery


Despite making significant advances in medical therapy, up to 70% of patients eventually require an operation. The leading indication for surgery is medically refractory disease manifested as an obstruction, fistulae, abscess, gastrointestinal bleeding, or perforation. In addition, less common indications for surgery include growth retardation in children, toxic megacolon, and fulminant colitis.




Preoperative Considerations


The decision to operate is made in the context of the patient’s preoperative nutritional status, immunosuppressive regimen, and any undrained sources of infection. Total parenteral nutrition (TPN) may be indicated if the patient is severely malnourished (defined as loss of more than 5% of body weight in 1 month or 10% in 6 months, a body mass index less than 19 kg/m 2 , or an albumin level less than 3 g/dL) to achieve improvement in wound healing and prevention of anastomotic leaks. This finding was demonstrated in a study of 395 malnourished patients who received 1 week of TPN prior to surgery and had significantly fewer noninfectious complications as compared to the controls (5% vs. 43%).


The impact of immunosuppressive medications on postoperative complications remains controversial. Recently, there has been a heightened focus on whether biologic therapy increases postoperative complications; while anti-TNFα therapy’s impact on postoperative complications remains controversial, a recent metaanalyses including up to 18 studies concluded infliximab was associated with an increased rate of postoperative complications, reported at a rate of 15%–17%. Our recent analysis of postoperative infectious complications associated with vedolizumab administration within 12 weeks of an abdominal operation found vedolizumab to be an independent predictor of postoperative infectious complications, with a 30-day surgical site infection rate of 36% (unpublished data). Thus, the timing of surgery as it relates to the most recent dose of biologic therapy becomes important to consider, as does consideration for diversion in the setting of a primary anastomosis.


Patients with abscesses should be drained nonoperatively with interventional radiology prior to going to the operating room, unless contraindicated due to need for emergent surgery. For intraabdominal abscesses, adequate drainage may obviate the need for surgery altogether; if not, it at least minimizes the degree of intraabdominal inflammation allowing for a more limited bowel resection. If infection or abscesses are present at the time of the operation, the surgeon should consider postoperative antibiotic therapy and delayed closure of operative incisions.


Once it is decided that the patient will proceed with surgery, the surgical plan should incorporate detailed information from imaging, endoscopy, and prior operative reports. Cross-sectional imaging with CT enterography (CTE) or MR enterography (MRE) provides important information about the distribution and extent of disease, any undrained fluid collections, anatomic location of fistulizing disease, alteration in anatomy due to prior operations, and an estimate of remaining small bowel length. MRE has the added advantage of no radiation with improved anatomic detail, especially important in this young population who will likely require several repeat abdominal images over the course of their lifetime.


A final important step prior to taking a patient to the operating room is a discussion regarding the potential construction of a permanent or temporary stoma. Because anxiety around stoma formation is common among CD patients, early comprehensive education and support from an enterostomal therapist is important. Additionally, it is important to consider preoperative stoma marking if the patient has any suspicion of requiring a stoma, especially in complex reoperative CD where unexpected intraoperative findings or technical difficulties may mandate stoma construction.




The Initial Operation


The initial operation for CD should focus on bowel preservation, careful measurement, and description of remaining bowel, use of a minimally invasive approach, and prevention of disease recurrence.


Disease Recurrence


Within 1 year of surgery, subclinical endoscopic recurrence occurs at the anastomosis in 90% of patients with CD, symptomatic clinical recurrence occurs in 30%, and 5% of patients will require another operation. Over time, approximately 70% of patients who have had operations need further surgery. Smoking, perforating disease, and previous resection have been identified individually from retrospective studies as risk factors for earlier postoperative recurrence, but these factors have not been used to tailor postoperative initiation of medical therapy. Recurrent mucosal disease after an operation typically precedes any clinical symptoms, and its severity predicts the subsequent clinical disease. Therefore, early endoscopy may be useful in earlier initiation and more aggressive use of postoperative medical therapy.


From a medical point of view, there is conflicting data regarding the use of postoperative prophylaxis. In general, patients considered high risk (e.g., smokers, perforating disease) should resume anti-TNFα therapy. Patients who have few risk factors may benefit from 3 months of antibiotics and followed with endoscopy at 1 year. And, those with no risk factors are generally rescoped at 1 year to assess mucosal disease. Methods to stratify patients into high- and low-risk populations combined with prophylaxis tailed to endoscopic recurrence would be ideal, but remains undefined. Thus, for most patients, a decision to give medical prophylaxis following resection needs to be individualized. From a surgical perspective, margin status at the time of resection, anatomic configuration of the anastomosis at the time of surgery, handsewn versus stapled anastomosis, and the use of strictureplasty have all been discussed with regard to prevention of disease recurrence.


Resection Margin


Because 1-year endoscopic recurrence is as high as 90% within 1 year of bowel resection, margin status has been a hotly debated topic to prevent disease recurrence. Historically, it was thought that perhaps microscopic and macroscopic margins were required to prevent disease recurrence. And, prior retrospective reviews have shown disease-free margins of 4 cm or “radical” disease-free margins of 10 cm compared to placebo had a lower recurrence rates and even improved quality of life. However, later larger studies and prospective studies showed no difference in recurrence rate based on resection margin. And, more recent data, looking at the importance of microscopic disease-free margins, has not found a difference in recurrence based on microscopic margins. Additionally, in the only randomized study to date, Fazio et al. evaluated the recurrence in 131 ileocolectomy patients randomized to undergo resections with proximal margins either 2 or 12 cm from the macroscopically diseased tissue followed up for median of 56 months; clinical recurrence was demonstrated in 33% versus 29% of those with limited and extended resections respectively, and no relationship was found between microscopic CD found at the resection margin and disease recurrence. Thus, standard practice today is to resect all gross macroscopically involved bowel and leave “positive margins,” or microscopically involved bowel, in place. This aligns with the importance of bowel preservation among patients with CD.


Recently there has been growing interest around resecting diseased mesentery to remove all gross disease and prevent recurrence at the anastomotic site. This comes from the work of several authors identifying that mesenteric fat hypertrophy is associated with a more aggressive CD phenotype regardless of change in weight, that the degree of visceral fat tissue correlates with the degree of inflammation, fibrosis, and stricture formation, and that visceral fat correlates with Crohn’s Disease Activity Index (CDAI) and C-reactive protein levels. Additionally, higher visceral fat volumes are associated with increased hospitalization and surgery. These findings suggest that it may be just as important to remove diseased mesentery as it is diseased bowel. However, the margin status of diseased mesentery has yet to be studied in terms of disease recurrence.


Type of Anastomosis


Nearly 10% of the ileocolic resections will require another operation for recurrent CD at the anastomosis. Thus, a recurrent question is whether the configuration or material used to perform the anastomosis at the time of ileocolic resection affects disease recurrence.


Overall, no anastomotic type has been found to be superior to another in patients with CD. However, a few basic principles should still be kept in mind and applied when appropriate. One is the lumen diameter following the anastomosis. It was originally thought that the wider the lumen, the less risk of stasis, bacterial overgrowth, mucosal disruption, and subsequent recurrence. While some studies including a recent metaanalysis have found a decreased risk of clinical and surgical recurrence at the anastomosis with a side-to-side anastomosis, others have found equivalent rates of recurrence with a side-to-side as compared to an end-to-end anastomosis. A multicenter randomized evaluation of end to end versus side to side found equivalent endoscopic recurrence (42.5% vs. 37.9%; P = 0.55) and a symptomatic recurrence rate (21.9% vs. 22.7%; P = 0.92) in the end-to-end compared with side-to-side group at 12 months after resection. This suggests that the anatomic configuration and luminal diameter does not affect disease recurrence. The second concept is stapled versus handsewn anastomosis. A number of studies have investigated this topic and found no difference in disease recurrence. An updated Cochrane review comparing handsewn and stapled anastomoses did a subgroup analysis of CD and found no difference in the postoperative stricture, anastomotic hemorrhage, anastomotic leak, reoperation, intraabdominal abscess, wound infection, length of stay, or mortality rate. Thus, there is no obvious advantage of a handsewn versus stapled anastomosis when performing an ileocolic resection. The third concept is bowel lumen size discrepancy between the two cut ends of bowel. In the setting of significant size discrepancy, an end-to-end anastomosis may be more challenging to perform than a side to side. Fortunately early postoperative outcomes are comparable with regard to anastomotic leak rate and surgical site infection. To date, since none of the commonly performed anastomotic techniques are favored with regard to recurrence of CD at the anastomotic site, the type of anastomosis constructed can be individualized at the time of the operation based on intraoperative findings.


Simultaneously, techniques to minimize disease recurrence are currently under development. The Kono-S, the antimesenteric functional end-to-end handsewn anastomosis, is one such novel technique. This technique utilizes a linear stapler to transversely divide the tissue for resection. The corners of the two stapled lines are sutured together and antimesenteric longitudinal enterotomies are created on both sides. The enterotomies are then closed transversely in two layers resulting in an antimesenteric functional end-to-end anastomosis ( Fig. 21.1 ). This technique has shown promise in a small cohort of 18 patients, 43% of whom have undergone follow-up endoscopic surveillance with an average Rutgeert’s score of 0.7 (0–3) at a mean of 6.8 months.




Figure 21.1


Kono-S, the antimesenteric functional end-to-end handsewn anastomosis.


Strictureplasty


Alternatives to bowel resection for fibrostenotic disease include endoscopic dilation (discussed in Chapter 13 ) and strictureplasty. Strictureplasty is indicated in clinical scenarios with multiple segments of fibrostenotic disease, long segments of stenotic disease, or when bowel length is already compromised from prior resections. Contraindications to strictureplasty include the presence of a perforation, fistula, abscess, or significant inflammatory changes at the stricture site. The main disadvantage of strictureplasty is the concern for malignant transformation at the strictureplasty site because the active disease has not been removed. However, the actual rate of small bowel carcinoma at the strictureplasty site is exceedingly low ranging from 0.21% to 0.34%. Interestingly, a potential advantage of strictureplasty may be mucosal healing at the stricutreplasty site without resection of diseased bowel.


The first reported strictureplasty for the treatment of CD was by Lee and Papaioannou in 1982. Since then, many techniques for strictureplasty have been described, and more surgeons are advocating the use of strictureplasty in place of resection for first-time ileocolic disease due to bowel preservation and the aforementioned mucosal healing. For strictures less than 4–5 cm in length, a Heineke–Mikulicz (HM) technique can be used, opening the stricture longitudinally and closing the bowel wall transversely ( Fig. 21.2 ). Two sutures are placed at the midpoint of the stricture, to be used as stay sutures to open the strictureplasty. An antimesenteric longitudinal incision is made over the stricture using cautery and extended onto normal bowel of equal distance in both the directions. If the patient has had long-standing inflammation, or the stricture has been present more than 5 years, biopsy or the mucosa may be prudent to rule out dysplasia or malignancy intraoperatively as the presence of neoplasia would change the operation performed. The enterotomy is then closed in a transverse, two-layered, handsewn fashion. For strictures longer than 4–5 cm in length, a Finney strictureplasty can be used to prevent narrowing at the inlet or tension on the transverse closure. A Finney strictureplasty is similar to a side-to-side anastomosis, and is useful in the setting of a single long stricture or multiple short segment strictures in close proximity ( Fig. 21.3 ). Two options exist. First, if the strictured area is mildly stenotic and the bowel has remaining pliability, the strictured area can be opened and sutured to normal bowel in a handsewn, side-to-side fashion. The second option is to exclude the strictured segment by overlapping normal small bowel proximal and distal to the strictured segment. However, bacterial overgrowth may occur in the blind diverticulum created, and malignant degeneration can occur in the excluded segment of small bowel.


Dec 30, 2019 | Posted by in GASTROENTEROLOGY | Comments Off on Overview of Surgical Therapy for Crohn’s Disease
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