Journal of Visceral Surgery (2013) 150, 1928

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REVIEW

Ischemic colitis: The ABCs of diagnosis and surgical management

D. Moszkowicz , A. Mariani , C. Trsallet , F. Menegaux
Service de chirurgie gnrale, viscrale et endocrinienne, universit Paris 6Pierre-et-Marie-Curie (Paris VI), groupe hospitalier Piti-Salptrire, Assistance PubliqueHpitaux de Paris, 47-83, boulevard de lHpital, 75651 Paris cedex 13, France

KEYWORDS
Abdominal aorta aneurysm; Aortic surgery; Atherosclerosis; Colectomy; Colonic ischemia; Ischemic colitis

Summary Ischemic colitis (IC) is a rare condition. As ischemia is often transient and clinical symptoms are reversible, its exact incidence is unknown. In current clinical practice, two types of IC are described according to the severity: severe IC, with transmural colonic ischemia and/or multi-organ failure (MOF), and mild IC, without MOF and spontaneous favourable evolution in most cases. Two clinical contexts are encountered: spontaneous IC (SIC) and postoperative IC (POIC), mainly after aortic surgery. As there is no specic clinico-biologic symptom of IC, emergent CT-scan and rectosigmoidoscopy are required for diagnosis conrmation, surgical decision and prognosis analysis. IC surgical treatment is not consensual but can be standardized according to organ function and the degree of ischemia: surgical treatment in case of colonic necrosis with deep ischemia and/or MOF; observation for supercial ischemia without organ dysfunction; systematic medical care. Surgery is required in 20% of cases, and consists in extended colectomy without continuity restoration and prophylactic cholecystectomy. Continuity restoration is feasible in one third of survivors, who are exposed to a high risk of severe cardiovascular events. 2013 Elsevier Masson SAS. All rights reserved.

Corresponding author. Tel.: +33 14 21 76 639. E-mail address: fabrice.menegaux@psl.ap-hop-paris.fr(F. Menegaux).

1878-7886/$ see front matter 2013 Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.jviscsurg.2013.01.002

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D. Moszkowicz et al. ischemia with colonic necrosis and/or MOF and observation and medical management of patients with supercial ischemia without organ dysfunction. Surgery is required in 20% of cases, and consists of extended colectomy without continuity restoration; prophylactic cholecystectomy is also recommended. Continuity restoration is feasible in one third of survivors. Patients are at long-term risk for severe cardiovascular events.

KEY POINTS Ischemic colitis (IC) develops in two classically recognized circumstances: IC may occur spontaneously or postoperatively, most commonly after aortic surgery. These two entities should be managed in the same way. In any elderly patient with an emergency presentation of incomplete bowel obstruction, with or without fever, with or without bloody diarrhea, even mimicking diverticulitis or acute intestinal obstruction, the diagnosis of spontaneous IC should be considered; delay in diagnosis and management is a major prognostic factor. The clinical and laboratory signs associated with IC are non-specic, so urgent abdominal CT scan and sigmoidoscopy are needed to conrm the diagnosis, to assess the need for surgery and to determine the prognosis of the disease. Bowel preparation is not necessary before endoscopy; a simple enema is sufcient to clear the distal colon. Once the diagnosis of IC is made, we have found that surgical indications depend on systemic impact (presence of multi-organ failure [MOF]) and the mural depth of ischemia as assessed by rectosigmoidoscopy: surgery is indicated for all Favier Stage 3 and for Stage 2 with MOF, while monitoring and supportive care are indicated for Stage 2 without MOF and for Stage 1 patients. Surgery is necessary in 20% of cases and consists of colectomy of varying extent based on preand intra-operative ndings without restoration of intestinal continuity (RC); prophylactic cholecystectomy is also performed. The average mortality reported is 6% in medically treated patients and 39% in surgical patients. Restoration of gastrointestinal continuity is possible at an interval after the acute episode in about one third of the survivors and should be considered after weighing the benets and risks, including risk-assessment after anesthesia. Recurrences are unusual and late deaths after colectomy are mostly due to cardiovascular disease. Secondary prevention of cardiovascular risk is essential.

General considerations and epidemiology

IC is the most common gastrointestinal vascular disease (5060% of cases) and a common cause of lower gastrointestinal bleeding [5]. The incidence in the general population ranges from 4.5 to 44 cases per 100,000 persons per year [6]. It typically occurs after the age of 60 [7], and patients with SIC were signicantly older than patients with POIC (73 years versus 68 years in our experience). SIC occurs more frequently in women and POIC in men [8]. POIC occurs most commonly after aortic surgery or after cardiac surgery with temporary gastro-intestinal vascular exclusion [9]. It occurs in 0.3 to 10% of patients undergoing infrarenal aortic surgery and is responsible for 10% of postoperative deaths [10]. For example, in a series of 1786 aortic reconstructions performed at our center, POIC developed in 2.7% of cases [11]. After endovascular repair of aortic aneurysm, the incidence is lower, estimated at 1.4% of cases [12].

Pathophysiologyetiology
IC consists of a spectrum of injuries arising from colonic wall ischemia due to inadequate regional blood ow [13]. The main pathophysiologic mechanism implicated is an ischemia-reperfusion phenomenon, with rapid return of normal mesenteric blood ow; this makes angiography an unreliable diagnostic test. The etiologic context is varied (Table 1) but in all cases results in local hypoperfusion with colonic tissue hypoxia that may progress, in the absence of appropriate treatment, to multi-organ failure. True occlusive IC is rare; it arises from arterial occlusion (stenosis or thrombosis of atherosclerotic vessels), proximal arterial ligation or exclusion, or venous occlusion. Most cases of IC are due to impairment of the micro-vascularization of the colonic wall [14,15]. This is not a true arterial occlusion, but rather a low-ow state with decreased colonic arterial perfusion, often secondary to increased intraluminal pressure and/or splanchnic vasoconstriction [16]. This phenomenon is similar to that which leads to acute acalculous cholecystitis where ischemia of the gallbladder wall occurs without occlusion of the cystic artery. This constitutes a theoretical justication for systematic cholecystectomy whenever colonic resection is necessary for IC. Colonic ischemia is usually segmental, predominately involving the left colon in 80% of cases (splenic exure: 25% sigmoid: 55%) while the right colon is involved in only 10 to 25% of cases. IC involving the entire colon occurs in less than 10% of cases but is more common in severe IC. Extensive arterial collateral vascularization makes the colon relatively protected from ischemia. Three anatomical zones are classically described as being at most risk for ischemia in the case of congenital absence of the marginal vascular arcade at each level [7,17]: the splenic exure at Grifths point where the marginal artery of Drummond interconnects the

Introduction
Ischemic colitis (IC) is a rare condition. As ischemia is often transient and clinical symptoms are reversible, its exact incidence is unknown [1]. Although impaired colonic blood supply can be explained by anatomical and pathological factors, the exact pathophysiology is still debated. In current clinical practice, two types of IC are described, dened by their severity: severe IC with transmural colonic ischemia and/or multi-organ failure (MOF), and mild-moderate IC without MOF, that evolves favorably without treatment in most cases. Two clinical contexts are encountered: spontaneous IC (SIC) and postoperative IC (POIC), mainly after aortic surgery [24]. There is no overall consensus regarding treatment of IC; treatment guidelines can be standardized depending on the depth of colonic mural ischemia and its impact on vital functions: surgical treatment in case of deep

Ischemic colitis: The ABCs of diagnosis and surgical management Table 1 Etiologic pathology of ischemic colitis (IC). Non-occlusive IC Threatened infarction (venous congestion with ischemia) Thrombosis of the mesenterico-portal venous axis Portal hypertension Colonic low-ow state

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Occlusive IC Infarction (arterial ischemia)

Arteriography

Shock

Hypovolemia, anaphylaxis, septic shock

Infra-renal aortic surgery with sacrice of the inferior mesenteric artery (IMA) Systemic vasculitis (lupus, polyarteritis nodosa, Takayasus, disease, thrombo-angiitis obliterans [Buergers disease]) Diabetic angiopathy Amyloid angiopathy

Surgery with cardio-pulmonary bypass, ECPB Vasoactive medications, pressors Digitalis, diuretics, NSAID medications, stimulant laxatives, estrogens, neuroleptic medications, catecholamines, anti-motility medications

Mesenteric thrombophlebitis

Acute pancreatitis Thrombophilia

Hemodialysis Obstruction Occluding tumor, Ogilvies syndrome (pseudo-obstruction) Cocaine use, long-distance runners

Radiation vasculitis Thrombophilias (Protein C or Protein S deciency, Factor III [anti-thrombin deciency]) Infections (Cytomegalovirus, Escherichia Coli O157:H7)
ECPB: extra-corporeal cardiopulmonary bypass.

Other

right, middle, and left colic arteries; the right colon, where the arcade connects the superior branch of the ileocolic artery with the inferior branch of the right colic artery; and the recto-sigmoid junction at Sdecks point where the sigmoidea ima artery interconnects the caudal sigmoid artery with the superior rectal artery.

Analysis of risk factors (RF)

All clinical settings compatible with the diagnosis of IC should be considered suggestive, particularly when there are recognized RF for IC. In an epidemiological case/control study comparing 700 patients with IC versus control subjects, IC patients had three times more functional bowel disorders (OR = 2.75) and were taking anti-motility medications in one of three cases versus one of nine cases in control patients (OR = 2.29) [18]. A history of cardiovascular disease was signicantly associated with the occurrence of IC and has been recognized as a risk factor in several studies despite a low level of evidence (retrospective series, case-control studies). In a case-control study comparing 161 patients with IC to 322 control subjects, type-2 diabetes, dyslipidemia, peripheral artery occlusive disease, coronary artery disease, heart failure, digitalis use, and aspirin use were independent RF for IC [19]. Other classical RF have been identied in these studies: age over 65 years, female sex, chronic obstructive pulmonary disease [6], inammatory bowel disease, constipation [20], history of cancer [21], hepatitis C viral infection (with cryoglobulinemia) [22]. The role of nonsteroidal anti-inammatory drugs (NSAID) in the genesis of IC is debated, but its association has not been found to be statistically signicant in most surgical series [18,23,24]. In a series of 80 patients with IC, lower abdominal pain with or without lower GI bleeding, age over 60 years, hemodialysis, hypertension, type-2 diabetes, hypoalbuminemia, and use

Diagnostic approach
Diagnostic strategy varies depending on the clinical presentation of IC (SIC or POIC), the extensiveness of colonic involvement, the depth of mural involvement, the acuteness of onset, the possibility of spontaneous recovery, and variations in vascular anatomy. Two clinical entities are typically dened based on evolution and management [3]: fulminant gangrenous IC (15%) characterized by transmural colonic necrosis progressing to colonic perforation, multi-organ failure, and rapid death if urgent surgical is not undertaken; non-gangrenous IC (NGIC) or acute transient IC (85 %). This is often reversible with 20 to 15 days of symptomatic treatment, but may also quickly progress to MOF, which becomes the determining factor in short-term prognosis and may require urgent surgical intervention. For nonoperated survivors with favorable progression during the initial phase, IC may evolve towards a chronic inammatory colitis or segmental stricture.

22 of anti-motility medications were present in 40% of cases versus 8% in 320 controls (OR = 9.3, P < 0.05) [24]. In this series, all patients with four RF, 76% of patients with three factors, 55% with two factors and 22% with only one factor proved to have IC. In another study, the independent RF associated with the diagnosis of IC in patients with lower GI bleeding were the occurrence of in-hospital bleeding, chronic renal failure and female gender [25]. The literature does not measure the relative importance of these factors in the occurrence of SIC or POIC; in our experience, these factors were not associated with the occurrence of IC in a statistically signicant way due to lack of power [8].

D. Moszkowicz et al. been tested but their sensitivities and specicities are inconsistent and do not permit practical recommendations [7,38,39].

Radiological diagnosis
Mesenteric angiography, long considered the gold standard for the evaluation of vascular pathology of the digestive tract, has no place in the diagnosis of IC (except for mesenteric infarction where it can lead to endovascular revascularization of the small bowel). Alteration of intestinal blood ow is often transient and ow may have already returned to normal at the time of symptom onset. The presence or absence of angiographic abnormalities does not seem to correlate with disease prognosis [3]. Urgent barium enema has now been abandoned in favor of abdominal CT scan with IV contrast (if there is no contra-indication to contrast injection); this has become the gold standard for diagnosis of suspected colonic pathology. It is readily available in an emergency, easily interpretable by the surgeon, and has acceptable cost and risks. CT signs of colonic involvement include the target or double halo appearance caused by hyperdensity of the mucosa and muscularis with submucosal edema, shaggy irregular contours, and mesenteric inammation with dirty fat; the viability of colon can also be assessed (kinetics of mural enhancement); signs of severity include pneumatosis intestinalis, portal air, free peritoneal uid or pneumoperitoneum indicating perforation. In addition, the extent of colon involvement can be assessed (Fig. 1) [40]. However, CT may be disappointing because it lacks specicity; frequently, it is the clinical context and the presence of RF that actually guide the therapeutic management. Typical ndings of IC are moderate continuous circumferential thickening of the colonic wall (< 1 cm, 8 mm average) with a moderately long segmental involvement (19 cm on average) with loss of haustrations; this occurs predominantly on the left [27]. CT is not reliable for the detection of mesenteric circulatory abnormalities. In addition, the combination of systemic low-ow state, microvascular abnormalities and reperfusion injury makes it difcult to correlate the length of colonic involvement with the distribution of the superior and inferior mesenteric arteries [14]. In a series of 44 patients with IC by Balthazar et al., 81% of patients with segmental ischemia had no CT evidence of macrovascular abnormality. Abdominal ultrasound has little practical utility in the emergency diagnosis of IC, although ultrasound ndings suggestive of IC have been described in conjunction with Doppler ow evaluation of the colonic vasculature [41].

Clinical diagnosis
The clinical signs are nonspecic. The most common functional symptoms are pain, (usually of sudden onset and moderate severity) and lower GI bleeding (rarely heavy but often accompanied by urgent diarrhea) [2628]. Abdominal distention is often present, associated with vomiting due to an associated ileus. A systemic inammatory response syndrome is usually present (fever, tachycardia and tachypnea). Thus, IC should be considered in the differential diagnosis in all elderly patients who present with an acute onset of incomplete bowel obstruction with atypical progression, with or without fever and diarrhea; IC can mimic diverticulitis or acute intestinal pseudo-obstruction. The diagnosis of SIC should be considered to avoid delay in management, a major risk factor for poor prognosis [29].

Ischemic colitis involving the right colon: an unusual entity

IC presents in the right colon in 10 to 25% of cases, usually as localized abdominal pain in the right lower quadrant or right gutter. It is often associated with coronary heart disease and dialysis-dependent renal failure, recognized factors of poor prognosis. Moreover, it carries a 2-fold greater mortality and 5-fold increased morbidity compared to other colonic localizations of IC [3033]. This poor prognosis can be explained in various ways: diagnosis is often delayed (less gastrointestinal bleeding); it is frequently associated with superior mesenteric artery (SMA) stenosis (with poor perfusion of the right colon); co-morbidities are frequently present including ischemic heart disease [30]. The combination of right colon IC and hemodialysis has been specically studied [30,34,35]. IC has been attributed to repeated episodes of hypotension resulting in microvascular vasoconstriction of the right colon. In this setting, any suspicion of IC should lead to prompt thorough investigation to avoid diagnostic delay. In a study of 60 patients with IC by Flobert et al., involvement of the right colon was the only independent risk factor associated with severe forms of IC. Right colon involvement was present in 82% of patients on renal dialysis and only 26% of non-dialysis patients (P < 0.05) [34]. A retrospective study of 77 patients that included nine patients with chronic renal insufciency and seven dialysis patients showed an 8.5-fold increased risk of unfavorable outcome for men with chronic renal insufciency [36], justifying a more aggressive diagnostic and therapeutic attitude.

Endoscopic diagnosis
Because clinical and laboratory signs of IC are nonspecic, endoscopy is necessary for diagnosis [42,43]. This must be done as an emergency, even in patients with unprepared colon. A simple enema achieves adequate cleansing to visualize the rectum and lower sigmoid, which can be accomplished in 90% of cases. Insufation must be prudent but the use of CO2 is not required. Colonic endoscopy is the most sensitive diagnostic test for IC, although interpretation is sometimes difcult since medication-induced colitis may mimic IC [44]. A sharp demarcation between normal mucosa and pathological areas (patchy involvement) may help in the diagnosis [45], as well as the topographical location of the lesions, predominating in the sigmoid [2]. Other ndings include segmental erythema, edema, hemorrhagic submu-

Laboratory ndings
Neither leukocytosis nor lactic acidosis has sufcient predictive value for diagnosis [37]. Many biomarkers have

Ischemic colitis: The ABCs of diagnosis and surgical management

23

Figure 1. A. CT with coronal reconstruction in a 74-year-old female hospitalized with left lower quadrant abdominal pain and lower GI bleeding and associated multi-organ failure; there is necrosis of the sigmoid colon (lack of enhancement of the bowel wall with contrast injection). B. Intra-operative appearance of transmural ischemic necrosis of the transverse colon.

cosal nodules (equivalent to thumbprinting on X-ray) progressing to mucosal erosions and extensive ulcerations in a geographic pattern, and occasionally circumferential conuent areas of necrosis. Other lesions can make diagnosis more difcult: pseudo-membranes, ischemic pseudo-polyps, cicatricial stenosis. The Favier classication of endoscopic ndings is useful in clinical practice [46]. It strengthens the diagnostic suspicion of IC and helps to assess the prognosis of disease and the likelihood of need for surgical intervention (Table 2, Fig. 2) [11,46,47].

Prognosis
The consensus in the literature denes poor prognosis for IC as mortality, need for surgery either immediately or after initial conservative management, or persistence of symptoms beyond 2 weeks [50]. There is therefore a need to identify the RF for mortality and failure of conservative treatment [51].

Results
Literature review reveals an overall mortality of 22% (653), ranging from 0% for patients treated conservatively to 75% for patients with pancolitis requiring emergency surgery. ICrelated postoperative death usually occurs within the rst 30 days [12,30]. The average mortality of patients operated for IC was 39.3% as reported in a literature review [52]. In our experience, where a majority of our patients underwent surgery (therefore, potentially having more serious disease), overall mortality was 48.7% (93/191) occurring at a median interval of 18.3 days. Patients who required colon resection had a mortality of 54% (84/174). Disease-specic mortality was 65.8% for Stage 3 disease with MOF and 16.6% for Stage 3 disease without MOF, 53.3% for Stage 2 disease with MOF and 0% for Stage 2 disease without MOF. Mortality was zero for patients with Stage 1 disease [8].

Pathological diagnosis
Performance of biopsies during colonoscopy is not necessary. Biopsy usually shows only non-specic ndings, so routine biopsy is no longer recommended. [48] Resection specimens of IC show a characteristic macroscopic loss of mucosal folds. On histologic examination, two pathognomonic signs of IC caused by ischemic necrosis are mucosal infarction and the presence of ghost cells (which retain their size and shape with disappearance of the cellular contents) [49]. The distribution of lesions is classically segmental and patchy following the natural distribution of ischemia along the colon. Other non-specic associated ndings include inltration of the necrotic mucosa and edematous submucosa by lymphocytes and hemosiderin-laden macrophages, mucosal erosions or ulceration, submucosal edema and hemorrhage, and submucosal microvascular thrombi [28].

Prognostic factors
IC that occurs following aortic surgery is typically considered to have a poor prognosis [53,54] (Table 3). In the series of 47 aortic surgeries by Longo et al., postoperative mortality was 50% in patients who developed IC (n = 3/6) [53]. In the historical series of Williams et al., mortality was 29% for SIC and 60% for postoperative IC [3]. Nevertheless, these results are based on small numbers and are not statistically significant. In our own experience, postoperative mortality did not differ signicantly between the two groups: 47% (n = 34) for SIC versus 42% (n = 50) for POIC (P = 0.42), probably because they were all managed by a standardized protocol [8]. A study of 112 patients with IC, 20 of whom had POIC, identied independent RF by multivariate analysis that included: a recent history of cardiac or vascular surgery with

Table 2 Stage 1

Favier endoscopic classication of IC [46]. Ischemia limited to the mucosa with petechiae and small ulcerations with intervening healthy mucosa Ischemia extending to the muscularis mucosa with large ulcerations Transmural ischemia with necrosis of the muscularis and possible perforation

Stage 2 Stage 3

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D. Moszkowicz et al.

Figure 2. Endoscopic appearance of various stages of ischemic colitis according to the Favier classication: A. Stage 1. B. Stage 2. C. Stage 3. (Reproduced with the kind authorization of Dr. X. Treton and Professor Y. Bouhnik).

aortic clamping (OR = 3.99, P < 0.05), and colonic evidence of severity (ulcers, mural necrosis) (OR = 3, 49, P < 0.05) [54]. In a French series of 77 patients who underwent emergency surgery for IC, 32 patients had a recent history of cardiovascular surgery and 33 had septic or hypovolemic shock; mortality was 28% in non-perforated IC and 53% in perforated IC [55]. Clinical RF for emergency surgery that have been identied in the literature include: male sex [56], hypertension [21], abdominal guarding [33,49,57,58], and absence of

Table 3 Risk factors for poor prognosis in patients with ischemic colitis. Epidemiology and past history Male gender Collagen vascular disease Chronic renal insufciency, dialysis Chronic constipation Cardiovascular risk factors or past history Other (cancer, COPD, hyperthyroidism) Clinical Lack of lower GI bleeding Signs of peritoneal irritation Multi-organ failure, shock Right colon involvement Involvement of the entire colon Laboratory ndings Anemia, hyponatremia Hypoproteinemia Leukocytosis Hyperlactacidemia > 2.5 mM/l Radiologic Pneumatosis intestinalis, portal venous air, pneumoperitoneum (CT scan) Loss of arterial ow in muscularis (Doppler US) Endoscopic Depth of ischemia (Favier classication) Necrosis, perforation Circumferential ulceration
COPD: chronic obstructive pulmonary disease.

lower gastrointestinal bleeding [57]. Rheumatoid arthritis, chronic renal failure, hemodialysis and right colonic [2,22,3134,49,56,59] or pancolonic [2,4,58] involvement are also associated with prolonged hospitalization and more frequent colectomy [34]. In an endoscopic series, solitary linear colonic ulceration was more frequently associated with IC (62% versus 7% in a control group of patients with IBD, infectious colitis and radiation colitis); this was more often associated with lower GI bleeding but the prognosis was favorable: these patients were less likely to require surgery (13% versus 27%) and had less mortality (4% versus 41%) than those with circumferential ulceration [60]. In a recent study of 153 patients with IC including 20 with severe disease, tachycardia (> 90 bpm), presence of shock in the last 24 hours, and ulceration seen by endoscopy were associated with severe IC in multivariate analysis [50]; when all three factors were present, the probability of severe IC was 74 times higher, with a sensitivity of 50% and a specicity of 93% (area under the ROC curve = 0.910). Several studies have identied the absence of lower gastrointestinal bleeding as an independent factor of poor prognosis [25,33,49,5658,61]. This may be partly due to the fact that patients with lower GI bleeding may present more promptly and receive supportive care and management earlier in the course of IC. The laboratory nding of elevated arterial lactate has been correlated with mortality in a recent study of 177 patients who underwent emergency surgery; the median preoperative plasma lactate level in survivors was 1.5 mM/l versus 3.3 mM/l in patients who died after surgery (P < 0.05). The authors established a lactic acidemia threshold of 2.5 mM/l as an unfavorable prognostic factor and included this parameter in a predictive mortality score that also included cardiac decompensation, acute renal failure, subtotal colectomy, and peri-operative administration of pressor agents; mortality ranged from 10.5% to 100% depending on the number of factors present [29]. Leukocytosis is not a specic nding in gastrointestinal ischemia. While it may be predictive of fulminant disease in patients over 60 years [21], it may also be absent in cases of frank colonic necrosis [58]. Anemia and hyponatremia are also considered RF of poor prognosis [61]. Imaging results also have prognostic value. The absence of arterial ow in the colon wall by Doppler ultrasonography is independently associated with complicated IC requiring surgery, with a sensitivity of 82%, a specicity of 92% and

Ischemic colitis: The ABCs of diagnosis and surgical management

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evolution. This treatment is sufcient in most transient cases of IC.

Monitoring during medical management

Medical management is based on ongoing surveillance of clinical ndings and endoscopic ndings. Colonoscopy can be repeated if the initial exam was reassuring to conrm the improvement of ischemia or, in the case of clinical worsening, to determine whether the endoscopic stage has worsened [11].

Indications for surgery

Evidence of colonic necrosis on CT scan (pneumatosis intestinalis, portal vein air, or free peritoneal air) is the classical indication for immediate surgery without the need of endoscopic conrmation. For patients undergoing endoscopy, visualization of irreversible necrosis of the colonic muscularis (Favier classication, Stage 3) should lead to emergency colectomy, even in the absence of organ failure. Similarly, patients with endoscopic evidence of less severe ischemia (Stage 2) should undergo surgery if the clinical condition evolves unfavorably despite medical management, particularly if MOF develops (acute renal or liver failure, shock, sepsis, lactic acidosis) and/or endoscopy shows progression to Stage 3 ischemia. Finally, the rare forms of IC with diarrhea, lower GI bleeding or exudative colitis that persist beyond 14 days can lead to discussion of colectomy [44].

Figure 3. Standardized decision algorithm for the treatment of ischemic colitis (IC). MOF: multi-organ failure.

positive and negative predictive values of 90% and 86% [41]. Signs of intestinal necrosis on CT (see above) are also associated with a poor prognosis [40].

Treatment
No studies with a sufcient level of evidence are available in the literature to establish clinical practice guidelines [51]; most studies have lumped IC together with mesenteric infarction. Few retrospective studies have focused specically on treatment, and they do not make practical recommendations regarding indications for surgery and the extent of colectomy [4,29,31,32,34,35,53,57,6264]. For severe cases, it is generally recognized that an aggressive surgical approach based on extensive colectomy is the only way to reduce mortality [2,11]. Our attitude to management is (Fig. 3) an aggressive surgical approach based on clinical and endoscopic ndings [8,11].

Emergency surgery
Complete exploration of the entire peritoneal cavity through a midline laparotomy is justied by the high incidence of hemodynamic instability related to MOF and the risk of secondary extension of ischemic lesions. Particular attention must be paid to the entire length of the colon and to the gallbladder. Peritoneal uid should be sent for culture. The general principle is to resect all necrotic segments of colon (Fig. 1). It is often difcult to dene the limits of colectomy unless transmural necrosis is present. Mesenteric vessels usually have palpable pulsation, even the small branches supplying the colonic wall. A macroscopic appearance of thickened, purplish, edematous colon is suspect. Proposed techniques to assess the quality of vascularization of the colon that one would hope to preserve include: Doppler ultrasound, colonoscopy with laser Doppler, photo-plethysmography, oxygen electrodes, pulse oximetry, and/or intravenous uorescein. Unfortunately, none of these techniques have demonstrated effectiveness and, practically speaking, they are difcult to perform in an urgent surgical setting [38,39]. Therefore, the colon should be transected beyond the macroscopically suspicious segment in an area that appears healthy and well-vascularized; there should be arterial bleeding from the transected edge of the muscularis and no evidence of colonic necrosis, although mucosal ulcerations are often present. In these criteria are not met, a more extensive colectomy should be performed. Given the difculties of precisely identifying the safe limits of resection and the severity of the disease, surgery for left-sided ischemia should consist of at least a left colectomy including both zones of precarious vascularization (splenic exure and rectosigmoid junction), and for the rare cases of

Medical management
All patients with suspected IC must be closely monitored if there are no indications for immediate surgery. In a recent literature review involving 1049 cases of IC, medical management was sufcient in 80.3% of patients and was associated with a mortality rate of 6.2% [52]. Management consists of digestive rest (to reduce the oxygen requirements of the colon), gastric suction for associated ileus, uid and electrolyte re-equilibration, prevention of venous thromboembolism, and use of broad-spectrum antibiotics. Antibiotic use is empirical and based on old experimental studies. They reduce the risk of bacterial translocation promoted by the loss of integrity of the colonic mucosa and limit the occurrence of necrotizing ischemia. Despite the lack of clinical evidence, antibiotic use is recommended by the American surgical societies [48]. Systemic corticosteroids are contra-indicated because they may potentiate IC and increase the risk of perforation [48]. To optimize colon perfusion, any aggravating factors such as vasopressors or digitalis should be avoided, and adequate cardiac output should be restored by volume resuscitation. Parenteral nutrition may be necessary in cases with prolonged

26 ischemia limited to the right colon, a right colectomy. Total colectomy should be performed for all other cases. Our proposals for clinical practice are: for IC involving the left colon: a Hartmann left colectomy including the splenic exure and rectosigmoid junction. The rectal stump is closed with staples and a left transverse colostomy is brought out in the left lower quadrant. Conservation of part (or all) of the rectum is warranted. Abdomino-perineal resection has no place in the surgical treatment of IC. While ischemia of the rectal mucosa is common (50%), it usually evolves favorably on its own [9] either healing as brosis or, at worst, developing breakdown of the rectal stump whose diagnosis and treatment pose few problems, although sometimes requiring re-operation; in the very rare cases of IC limited to the right colon: right colectomy with ileostomy and colostomy in the right lower quadrant; for widespread or pancolonic involvement: a total colectomy with terminal ileostomy and closure of the rectal stump. When right colon ischemia is associated with less pronounced ischemia on the left side, we recommend total colectomy because it is often indicative of extensive ischemia, with hypo-perfusion due to superior mesenteric arterial ischemia. In the latter case, small bowel ischemia usually dominates the picture and the management is quite different, involving extensive small bowel resection, colectomy, and any revascularization [65]. The management of this entity is still debated; systematic cholecystectomy prevents the development of resuscitation-related acute acalculous cholecystitis that might otherwise require re-operation in a fragile patient [66]. We admit, however, that this attitude is based on a low level of evidence. In our experience of 174 patients with IC who underwent surgery, we performed 96 total colectomies, 68 left colectomies and 10 right colectomies. SIC required extended colectomy more often (n = 25, P = 0.02). With the application of our decisional algorithm, only six of 174 patients in this series (3.4%) required re-operation to complete a total colectomy because of persistent colonic ischemia [8].

D. Moszkowicz et al. 80% if all six factors were present [68]. During surgery the surgeon should reduce as much as possible the duration of aortic cross-clamping, prevent hypotension, avoid damage to the peri-colic marginal arteries, and re-implant the IMA.

Long-term prognosis
Restoration of intestinal continuity (RC)
Very little data is available on RC after colectomy for IC. Longo et al. reported a series of 43 patients (without statistical analysis); for segmental IC, the surgical intervention rate was 65% (19/31) with RC in 75% (9/12), while all patients with pan-colonic ischemia (12/12) underwent total colectomy with a mortality of 75% and RC in only one of the three survivors [4]. Huguier et al. performed RC in 83% (5/6) of patients and Leardi et al., in 60% (3/5) of patients [57,69]. In our experience, among the 81 long-term survivors after colectomy for IC, the RC rate was 33% (27/81), after a median interval of 7.9 months (range: 0.2 to 35) [70]. RC was associated with acceptable morbidity (40%, 11/27), with no anastomotic leakage or re-operation (two wound infections, one lower GI bleed, four respiratory infections), and with no additional mortality. We recommend a multidisciplinary discussion between surgeons, anesthetists and cardiologists after the 6th month postoperatively to assess the risks of RC.

Long-term morbidity and risk of relapse

Longstreth et al. reported a series of 424 episodes of IC in 401 patients with a median follow-up of 2.6 1.9 years; 29 of these patients underwent surgery. In this series, there were no cases of chronic colitis, the rate of ischemic stenosis was 0.3%, and multiple episodes occurred in 6.7% (recurrence rate of 3%, 5%, 6% and 10% at 1, 23, 4 and 56 years, respectively) [56]. With a median follow up of 4.5 years, Huguier et al., reported an 8.6% recurrence rate (5/58) and 21% rate of mortality from cardiovascular causes (12/58) [57]. With a median follow up of 8 years, Leardi et al. reported no recurrences [69]. In a surgical series, 87 patients were followed for a median of 43 months [29]; at 31 months, 47 of 87 patients (54%) were alive, survival was 63% at 2 years and 18% to 5 years. One late death was attributed to IC, while 73% of deaths occurred due to cardiovascular causes. In this study, the extent of colectomy was not a poor prognostic factor for long-term survival in multivariate analysis; the only predictive criterion for long-term mortality was the presence of mesenteric atherosclerosis in the surgical specimen. In fact, 97% of patients who died during follow-up had atherosclerosis of the major mesenteric vessels versus 32% of survivors (P = 0.03); and these patients died one year sooner (median survival 40 versus 52 months P = 0.027). The presence of atherosclerosis in the mesenteric specimen is a marker for diffuse vascular disease and indicates the need to institute active secondary prevention of cardiovascular risks. In this context, the role of angiotensin converting enzyme inhibitors remains to be dened [15].

Prevention and monitoring in cardiovascular surgery

Following major vascular surgery, particularly aortic reconstruction, the onset of diarrhea (with or without bleeding) or unexplained organ failure mandates sigmoidoscopic evaluation [38]. If moderate ischemic lesions are seen endoscopically, the examination should be promptly repeated (within 12 hours) to monitor the evolving ischemic process [67]. Revascularization of the occluded inferior mesenteric artery (IMA) during aortic surgery has been proposed but its possible benecial effect could not be demonstrated. However, it is clear that the patent IMA must be re-implanted along with superior mesenteric revascularization if the SMA is not patent and the mesenteric arterial network is entirely dependent on the IMA [9]. Scores have been proposed to calculate the risk of IC after abdominal aortic aneurysm rupture, taking into account a variety of peri-operative factors (systolic blood pressure < 90 mmHg, hypotension for more than 30 minutes, temperature < 35 C, pH < 7.3, > 6 units of blood transfusion, IV uid resuscitation exceeding 5 l). The risk of developing IC was 48% if two factors were present and

Late complications
Persistence of segmental ischemia can lead to the formation of ischemic pseudotumors of the colon or rectum whose endoscopic appearance may mimic that of adenocarcinoma and whose diagnosis is most often made retrospectively on

Ischemic colitis: The ABCs of diagnosis and surgical management the surgical specimen [71]. Only a few such cases have been reported [72]. Ischemia involving the colon muscularis may lead to ischemic stricture. Only symptomatic strictures (obstruction, liquid stools, bleeding) require surgery, especially since these lesions may disappear spontaneously after 12 to 24 months [73]. Endoscopic dilatation is a therapeutic alternative, although its effectiveness has not been fully evaluated.

27
aneurysm repair: a 10-year retrospective study. Arch Surg 2009;144:9003. Barbagelatta M. Anatomic-pathologic diagnosis of ischemic colitis. J Chir (Paris) 1997;134:97102. Balthazar EJ, Yen BC, Gordon RB. Ischemic colitis: CT evaluation of 54 cases. Radiology 1999;211:3818. Carlson RM, Madoff RD. Is ischemic colitis ischemic? Dis Colon Rectum 2011;54:3703. Reilly PM, Wilkins KB, Fuh KC, Haglund U, BulkGB. The mesenteric hemodynamic response ley to circulatory shock: an overview. Shock 2001;15: 32943. Paterno F, Longo WE. The etiology and pathogenesis of vascular disorders of the intestine. Radiol Clin North Am 2008;46:87785 [v]. Walker AM, Bohn RL, Cali C, Cook SF, Ajene AN, Sands BE. Risk factors for colon ischemia. Am J Gastroenterol 2004;99:13337. Cubiella Fernandez J, Nunez Calvo L, Gonzalez Vazquez E, et al. Risk factors associated with the development of ischemic colitis. World J Gastroenterol 2010;16:45649. Huerta C, Rivero E, Montoro MA, Garcia-Rodriguez LA. Risk factors for intestinal ischaemia among patients registered in a UK primary care database: a nested case-control study. Aliment Pharmacol Ther 2011;33:96978. Barouk J, Gournay J, Bernard P, Masliah C, Le Neel JC, Galmiche JP. Ischemic colitic in the elderly: predictive factors of gangrenous outcome. Gastroenterol Clin Biol 1999;23:4704. Mosele M, Cardin F, Inelmen EM, et al. Ischemic colitis in the elderly: predictors of the disease and prognostic factors to negative outcome. Scand J Gastroenterol 2010;45:42833. Petit A, Guedon C, Duhamel C, Lerebours E, Colin R. Ambulatory ischemic colitis. Clinical course and etiologic features in 88 cases. Gastroenterol Clin Biol 1990;14:73943. Park CJ, Jang MK, Shin WG, et al. Can we predict the development of ischemic colitis among patients with lower abdominal pain? Dis Colon Rectum 2007;50:2328. Chavalitdhamrong D, Jensen DM, Kovacs TO, et al. Ischemic colitis as a cause of severe hematochezia: risk factors and outcomes compared with other colon diagnoses. Gastrointest Endosc 2011;74:8527. Theodoropoulou A, Koutroubakis IE. Ischemic colitis: clinical practice in diagnosis and treatment. World J Gastroenterol 2008;14:73028. Taourel P, Aufort S, Merigeaud S, Doyon FC, Hoquet MD, Delabrousse E. Imaging of ischemic colitis. Radiol Clin North Am 2008;46:90924 [vi]. Zou X, Cao J, Yao Y, Liu W, Chen L. Endoscopic ndings and clinicopathologic characteristics of ischemic colitis: a report of 85 cases. Dig Dis Sci 2009;54:200915. Reissfelder C, Sweiti H, Antolovic D, et al. Ischemic colitis: who will survive? Surgery 2011;149:58592. Brandt LJ, Feuerstadt P, Blaszka MC. Anatomic patterns, patient characteristics, and clinical outcomes in ischemic colitis: a study of 313 cases supported by histology. Am J Gastroenterol 2010;105:224552 [quiz 2253]. Sotiriadis J, Brandt LJ, Behin DS, Southern WN. Ischemic colitis has a worse prognosis when isolated to the right side of the colon. Am J Gastroenterol 2007;102:224752. Medina C, Vilaseca J, Videla S, Fabra R, Armengol-Miro JR, Malagelada JR. Outcome of patients with ischemic colitis: review of fty-three cases. Dis Colon Rectum 2004;47:1804. ONeill S, Elder K, Harrison SJ, Yalamarthi S. Predictors of severity in ischaemic colitis. Int J Colorectal Dis 2012;27(2):18791. Flobert C, Cellier C, Berger A, et al. Right colonic involvement is associated with severe forms of ischemic colitis and occurs frequently in patients with chronic renal failure requiring hemodialysis. Am J Gastroenterol 2000;95:1958. Scharff JR, Longo WE, Vartanian SM, Jacobs DL, Bahadursingh AN, Kaminski DL. Ischemic colitis: spectrum of disease and outcome. Surgery 2003;134:6249 [discussion 62930].

[13] [14] [15] [16]

Conclusion
If there is clinical suspicion of IC, abdominal CT scan and sigmoidoscopy should be performed urgently to conrm the diagnosis, assess the need for surgery and determine the prognosis of the disease. Indications for surgery depend on the systemic impact (MOF) and the depth of ischemic lesions by colonoscopic assessment: surgery is necessary for parietal necrosis involving the deep layers of the muscularis and/or for multi-organ failure; supercial ischemia without MOF can be treated by close observation and medical management in all cases. Surgical intervention combines colectomy, stoma formation, and cholecystectomy. Restoration of continuity is possible in about one third of the survivors. Late recurrences are rare (10% at 5 years).

[17]

[18]

[19]

[20]

[21]

[22]

[23]

Disclosure of interest
The authors declare that they have no conicts of interest concerning this article.
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