Surgery-induced and Associated Long-term Strictures

Abstract

Strictures, commonly referred to as stenoses, are a rare but significant complication for patients who have undergone colorectal surgery. Strictures are difficult to diagnose due to variable clinical presentations, diverse etiologies, and lack of formalized diagnostic criteria. The clinical impact of strictures can be quite variable, ranging from a benign course not requiring intervention to emergent complications (e.g., bowel obstruction, perforation). Importantly, strictures can also have a large impact on patient quality of life and long-term bowel function. Once a stricture is diagnosed or clinically suspected, it is critical to determine its etiology to help guide clinical management and prevent recurrence. Strictures can be categorized as partial or complete, intrinsic or extrinsic, benign or malignant. We propose the ARCTIC mnemonic (Anastomosis, Radiation/Chemotherapy, Technical, Inflammation, and Compression) as a useful tool for remembering common stricture causes in the postoperative environment. This review seeks to provide an overview of the etiologies, diagnosis, and management of strictures in the postoperative setting.

For patients undergoing colon and rectal surgery, strictures occur when the intestinal lumen cannot achieve the diameter and/or elasticity of the adjacent healthy bowel on either side of the stricture site. ¹ Strictures are most likely to occur at the site of anastomosis but can occur anywhere along to bowel. While strictures in of themselves can be benign, secondary sequelae can be severe and life-threatening, including bowel obstruction requiring reoperation, perforation, pain, and altered long-term bowel function. ² To date, the overall prevalence of strictures after colon and rectal surgery is difficult to define but estimated to range from 2 to 30%, particularly those requiring bowel anastomoses. ^{2 3 4} Incidence is likely underreported as most are diagnosed long after the immediate postoperative period, typically between 4 and 12 months after an index operation. This is due to the time-lapse required for tissue remodeling and/or disease progression for a stricture to present itself. ^{3 5 6 7} Risk predictors for stenoses include distal anastomoses, obesity, postoperative abscess and/or anastomotic leak with resultant inflammation and infection, inflammatory bowel disease, and history of radiation/chemotherapy. ⁷ Anastomotic perfusion is also known to be important, with both systemic and anastomotic site hypoxia increasing the incidence of strictures. ^{8 9}

Patients who ultimately develop strictures will generally present with non-specific symptoms consistent with bowel obstruction, including nausea, vomiting, abdominal pain, distension, bleeding, and loose bowel movements. ¹⁰ Physical exam is often non-specific, with possible findings including signs of abdominal distension, tenderness, and possibly a palpable mass if there is associated inflammation or tumor. ¹¹ Short of a very distal stricture palpable on digital rectal examination, patients will need imaging and/or endoscopic procedures for definitive diagnosis and determination of etiology.

Etiology

Accurately diagnosing the etiology of stricture development is critical in helping to guide prevention and management. The most common causes of postoperative strictures can be categorized into one of five categories: anastomotic considerations, effects of perioperative radiation or chemotherapy, technical considerations during surgery, perioperative inflammation, or extrinsic compression ( Fig. 1 ).

Fig. 1.

ARCTIC (Anastomosis, Radiation/Chemotherapy, Technical, Inflammation, and Compression) mnemonic for recollection of common causes of stricture after colorectal surgery.

Anastomosis

While any location along the gastrointestinal tract is susceptible to stricture development, they are most likely to occur at an anastomosis with certain anastomotic-specific risk predictors. Anastomoses at watershed perfusion sites are prone to localized hypoxia, which can lead to stricture formation. ¹² In addition, the more distal an anastomosis is, the greater the risk for stricture development. ¹³ Interestingly, it has also been reported that anastomoses constructed by trainees are more likely to encounter strictures, possibly due to inexperience in the management of tissue tension and suture-induced hypoxia during anastomotic construction. ¹³ Of all anastomoses, ileoanal and ileal-pouch anal (IPAA) anastomoses are particularly prone to develop strictures. This is in part due to their distal nature and complex reconstruction that must support significant physiologic stressors. ^{14 15} Prior work suggests that ileoanal strictures are mostly nonfibrotic (86.4% of patients), emphasizing the role of technical proficiency during anastomosis constructions. ¹⁴ After IPAA, a greater number of strictures were observed after a handsewn anastomosis (12%) than after a stapled anastomosis (4%). ¹⁴ It is possible that this finding is related to patient-related complexity rather than technique alone. While the type of anastomosis may put patients at risk for stricture development, there is also a significant impact depending on the indication for the anastomosis. For example, patients who have undergone oncologic operations requiring anastomosis are at risk for malignant recurrence at the site of anastomosis. ¹⁶ Alternatively, patients with a history of Crohn's disease are at higher risk for anastomotic stricture secondary to inflammatory transmural disease. ¹⁷ In patients undergoing operative intervention for cancer, malignant recurrence resulting in stricture was more common in patients who experienced an anastomotic leak (12.9% vs. 5.7%). ¹⁶ While risk factors for anastomotic stricture need to be acutely considered, they are counterbalanced by the need to maintain hemostasis and restoration of intestinal continuity.

Radiation/Chemotherapy

All etiologies can appear as partial or complete strictures, but complete strictures are more likely to be associated with malignancy or receipt of radiation/chemotherapy. ^{7 9 18} Neoadjuvant radiotherapy is a well-known and significant cause of long-term sequelae after colon and rectal surgery. However, the rates of radiotherapy complications have significantly decreased in recent decades due to technical improvements in linear accelerators, such as the development of three-dimensional conformal radiation therapy, intensity-modulated radiotherapy, novel fractionation schemes, and the increasing use of radioprotective agents. ^{19 20} The development of radiation enteropathy depends on the radiotherapy dose, the treated volume, the fractionation schedule, and the follow-up time. Risk factors that worsen the chances of radiotherapy-related strictures include age, comorbidities, tobacco abuse, prior surgery, and simultaneous chemotherapy. ²¹ Importantly, some protocols are known to increase the occurrence of local complications, such as impaired anorectal function, following preoperative irradiation in patients treated with low anterior resection for rectal cancer. ²²

Technical

Anastomotic strictures can also occur as a result of failed approximation, tension along the bowel, or overly tight suturing/stapling, all potentially resulting in localized ischemia. ^{7 23} Prior work examining bowel tension as a predictor for stricture development has shown measurable technical factors at the time of IPAA that can predict strictures. Patients with shorter anal transitional zone, greater distance from the upper border of the symphysis pubis to the apex of the small bowel loop used for anastomosis, thicker abdominal wall at the stoma site, and longer distance from the pouch to the ileostomy were all more likely to have higher surgeon reported tension scores and subsequent strictures. ²⁴ Blood vessel ligation and management during operation is also critical to prevent strictures. For example, when performing a low anterior resection, mobilization of the splenic flexure and high ligation of the mesenteric vessels are associated with decreased stricture development due to the reduction of tension. ²³ Tension and blood vessel management, in of themselves, are associated with stricture development but likely are more directly a result of tension-induced hypoxia at the anastomosis. Hypoxia can also be induced locally by restrictive suturing/stapling or systemically from a variety of comorbidities (smoking, obesity, hypotension, lung disease, etc.). There is significant debate about whether anastomotic stapling versus hand suturing is more prone to stricture development from uncontrolled tissue ischemia and damage; however, due to patient and surgeon factors, it is difficult to definitively determine this from available literature. ³ Importantly, all of these considerations do not just apply to bowel-to-bowel anastomosis but also for ostomy construction and should be considered in both scenarios by the surgical team. ^{4 25}

Inflammation

Intrinsic strictures tend to come from inflammation (submucosal effect) or tissue damage (anastomosis, radiation, chemotherapy, etc.) undergoing remodeling and healing that results in partial occlusion of the lumen. ^{12 20} Patients who have undergone index operations due to chronic inflammatory disease such as Crohn's disease are more likely to develop strictures as a part of their continued disease process or impact of the inflammatory disease on the anastomosis. ^{26 27} As postoperative disease-based inflammation recurs, attempts to heal the damaged tissue can result in an excessive production of extracellular matrix components and deposition of connective tissue, thus favoring the formation of strictures. ¹⁷ Some promise has been shown in vitro for the medical management of these strictures using antifibrotic agents such as tranilast, peroxisome proliferator-activated receptor gamma agonists, rho kinase inhibitors, and mesenchymal stem cell therapy. ¹⁷ However, it is yet to be determined if these novel treatments have negative impacts on anastomotic healing, resulting in worse or alternative adverse outcomes. Inflammation can also occur from disease recurrence, such as that from diverticulitis. An operative principle to prevent the recurrence of diverticulitis is to resect the entire distal sigmoid colon and anastomose healthy proximal colon to the rectum. ²⁸ Inflammation resulting in stricture is also associated with anastomotic leaks, which are defined as the breakdown or insufficiency of the anastomosis resulting in spillage of intestinal contents outside of the bowel lumen. ^{9 13 29} Anastomotic leaks can present acutely with septic shock or chronically with a waxing-and-waning vague ileus-like presentation. In general, prevention of leaks requires complete closure of the anastomosis and limiting other factors that impair healing, such as the aforementioned tension and blood supply that may induce stricture through other mechanisms.

Compression

Malignancies that result in stricture can either be intrinsic or extrinsic in nature. Benign extrinsic strictures are rare but may result from mass effects on the bowel from a hematoma due to improper hemostasis or abdominal clearing of intraoperative bleeding. Additionally, abscess formation adjacent to anastomotic leaks may result in bowel compression. An acute (<2 weeks postoperation) development of anastomotic loss of patency should alert the clinician to external compression from a hematoma or abscess as a potential etiology. Malignant external compression tends to present with a more chronic picture. As discussed above, malignancy should also be suspected when anastomotic leaks occur after oncologic resection. Fortunately, etiology resulting in compression will often be readily visible using standard imaging techniques and is often the most easily diagnosed stricture type.

Diagnosis

Diagnosis of bowel strictures in the postoperative setting is challenging given the non-specific clinical findings and generic patient presentation. Most patients with a clinically significant stricture will present with symptoms of bowel obstruction and, therefore, often require advanced imaging and/or a diagnostic procedure to secure a diagnosis. Importantly, these symptoms may wax and wane depending on the severity/completeness of the stricture and ameliorating factors such as dietary compensations. Nearly all patients presenting with symptoms suspicious for bowel obstruction, which may be due to a stricture, will receive a computed tomography (CT) scan with contrast. It is important to note that those with a very low anastomotic stricture or those with stricture at an ostomy may require physical examination with digitization to diagnose. In some settings, sedation is required for tolerance of these procedures.

Imaging definitions for colorectal strictures are not uniform, but certain characteristics can give clues to the likelihood of a stricture and etiology. Short strictures (less than 10 cm) are more common in setting of cancer recurrence or anastomotic strictures secondary to anastomotic type, inflammation, or technical considerations. ^{26 30} Longer strictures (more than 10 cm) are more common with systemic inflammation (Crohn's), radiation/chemotherapy, ischemic stricture, or muscular hypertrophy in the case of recurrent diverticulitis. ³⁰ Other imaging modalities, such as ultrasound, can be effective in diagnosing strictures, but their utility in the postoperative setting is limited. ³¹ CT imaging with water-soluble contrast enemas have been extremely useful to evaluate for location and diameter of strictures. Stricture evaluation using contrast enemas have been shown to present with average diameters of 5.8 mm compared to the 15 mm in healthy anastomoses, with 8 mm being a standard diagnostic cutoff. ³² Contrast enemas also have the benefit of identifying if there is active extravasation from the bowel lumen to suggest an anastomotic leak. ³³ Contrast enemas can also be a useful preventative tool in which they are performed prior to ostomy site closure to identify strictures that can be intervened upon. ³⁴

Endoscopic evaluation is a critical diagnostic modality for colorectal stricture diagnosis, however, there are no standard metrics for diagnosis a stricture using endoscopy outside of a physician's expertise. It is generally accepted that the most clinically relevant strictures will not be passable by an endoscope.

Intraoperative and physical examination evaluation metrics have been established to evaluate strictures' severity based on digital examination. ¹ These metrics also play an important role in the diagnosis when a stricture is digitally palpable, possibly in the anorectum or ostomy sites. However, digital manipulation of accessible strictures sites is limited in its diagnostic utility and should be reserved for a small subset of strictures.

Management

Once the diagnosis of stricture has been made and the etiology is understood, there are several options for management: non-procedural, endoscopic intervention, or surgical intervention. These divergent management choices are not ultimate and do not preclude shifting management based on patient progression and new information. The timing and type of intervention depends on numerous factors, including the etiology of the stricture, the acuity or chronicity of associated symptoms, whether it results in a partial or complete obstruction, and patient clinical factors and preference. Intervention may take place in an elective, urgent, or emergent setting. Importantly, if recurrent malignancy is the suspected etiology, multidisciplinary discussions between surgical and medicine teams may be helpful to determine biopsy necessity, systemic treatment options, and whether resection or diversion would be necessary in the treatment algorithm.

Non-Procedural Management

Benign strictures essentially include all etiologies outside of malignancy and, therefore, can have very diverse management needs. In the setting of a patient with a benign partial stricture without an urgent surgical need, the first step is likely non-procedural management with dietary changes. Diet modifications may include smaller meals, softer foods, or adjusting fiber intake with the goal of avoiding food types and consistencies that would make stool more difficult to pass through the stenotic area. ³⁵ Generally, patient preferences will dictate that dietary modifications are only tolerable on a short-term basis. If a patient presents with a benign etiology resulting in a bowel obstruction, they may require temporary dietary modification or a nasogastric tube for decompression prior to endoscopic or surgical intervention.

Endoscopic Management

If nonoperative management with dietary changes and bowel rest is unsuccessful, procedural intervention is necessary. Management options are highly dependent on the location of the stricture and its etiology. Endoscopic interventions, including balloon dilation, stenting, or endoscopic stricturotomy or strictureplasty, can often be considered first-line interventions. Balloon dilation has been shown to be more effective than covered metal stents in Crohn's disease-associated strictures, though stents can be more effective in longer strictures. ^{36 37 38} Stents have also been utilized in malignant strictures, acting as a bridge to surgery to allow for preoperative optimization (bowel prep, nutrition, proximal bowel recovery) or a palliative option to improve quality of life. ³⁹ However, stenting does carry a risk of stent erosion, migration, or perforation, as well as patient discomfort associated with distal stents. Endoscopic interventions may also be limited by the ability to access the stricture; for example, the mid-small bowel is challenging to reach and often requires an experienced endoscopist to perform a double balloon enteroscopy. Endoscopic stricturotomy or strictureplasty has also shown promise in anastomotic and benign stricture management but may carry a slightly higher risk of bleeding than balloon dilation and similarly requires an experienced endoscopist and thus may not be available at every center. ^{40 41} Furthermore, patients must understand the potential need for several or recurrent procedures, as well as the rare but serious risk of perforation with the procedure. ⁴² For stomal or anal strictures, initial management with dilation can be done using Hegar dilators in the office or under anesthesia if needed, or if safe and well-informed, done by the patient themselves. Strictures caused by anastomotic leaks or in the immediate postoperative period should avoid these dilation procedures, given the significantly increased risk for perforation. Finally, if the stricture is chronic with an etiology likely to result in recurrence, endoscopic procedures should be considered a bridge to definitive surgical management rather than definitive.

Surgical Management

If non-procedural and endoscopic management options are unsuccessful or not feasible, as in the case of a complete bowel obstruction, surgery must be considered. Options for surgical intervention similarly depend on several factors, including the location and etiology of the stricture, patient clinical status, comorbidities, prior operations, and patient preference. If systemic disease is contributing etiology, such as systemic hypoxia or Crohn's disease, physiologic optimization prior to surgery may be required. Surgical intervention may include resection of the stenotic segment, stomal revision, anastomotic revision with or without diversion, strictureplasty, or fecal diversion. The specific operation that is performed is determined on an individualized patient basis. For severe stomal stenosis, which can occur at the skin or fascial level, local revision can be performed, though a laparotomy may be required for increased mobilization, and rarely, stoma translocation may be necessary. ^{25 43} In severe cases of stenosis, fecal diversion alone may be the only option.

Conclusion

Postoperative stricture formation following colon and rectal surgery can have a significant impact on patient management and quality of life. Etiology can vary greatly and can be better understood using the ARCTIC mnemonic and consideration of partial or complete, intrinsic or extrinsic, benign or malignant causes. Once diagnosed, management options include non-procedural, endoscopic, and surgical interventions. Advances in endoscopic techniques have allowed for more patients to be treated non-operatively, and it has shown to be a safe and effective alternative or bridge to reoperation. ^{27 44} Current studies are investigating endoscopic versus surgical intervention for stenosis in Crohn's disease, which will provide additional evidence for decision-making for these patients, ⁴⁵ and further endoscopic advances may allow additional patients to avoid reoperation. Importantly, shared decision-making and individual circumstances best determine management options for each patient.

Funding Statement

Funding M.J.F. was supported by T32 Funding from the University of Wisconsin Madison Medical Scientist Training Program from the National Institute of General Medical Sciences (T32 GM140935 and T32 GM008692) and the University of Wisconsin Microbes in Health and Disease from the National Institute of Allergy and Infectious Diseases (T32 AI055397). C.E.P. was supported by T32 funding from the University of Wisconsin Surgical Oncology Research Training Program (NIH, NIC T32CA090217). The content of this work is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or UW Hospitals and Clinics. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the views of the U.S. Department of Veterans Affairs or the United States Government.