SEARCH

SEARCH BY CITATION

Keywords:

  • Crohn's disease;
  • restorative proctocolectomy;
  • indeterminate colitis;
  • long-term outcomes

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Method
  5. Results
  6. Discussion
  7. References

Introduction  The present study aims to evaluate the short-term and long-term outcomes of patients undergoing restorative proctocolectomy (RPC) for Crohn's disease (CD) and Indeterminate colitis (IC) and to identify factors associated with adverse outcomes.

Methods  A descriptive study of 52 patients with CD or IC from a total of 1652 patients undergoing primary or salvage RPC in a single tertiary referral centre between 1978 and 2003. Primary outcomes were ileal pouch failure (excision or indefinite diversion), adverse events and functional outcomes (bowel frequency, urgency and continence).

Results  Patients with IC or IC favouring ulcerative colitis (Group 1, n = 26) had a pouch failure rate of 11.5%vs 57.5% for patients with CD or IC favouring CD (Group 2, n = 26). Pouch salvage surgery was undertaken in 15 patients with a 13.3% failure rate. Patients in Group 2 were 2.6 times more likely (95% CI: 0.96–7. No significant differences were evident between CD and IC patients with regards to pelvic sepsis (19.2%vs 15.4%), anastomotic stricture (23.1%vs 21.7%), small bowel obstruction (26.9%vs 26.9%) or pouchitis (15.4%vs 11.5%). The 24-h bowel frequency (7.5 vs 8), faecal urgency, daytime or night time incontinence were similar between patients with CD or IC..17) to develop a pouch-related fistula than patients in Group 1.

Discussion  Crohn's disease and to a great extent indeterminate colitis favouring CD were both associated with high failure rates and postoperative pouch-related fistula rates. Despite these problems, functional outcomes for patients with CD or IC were similar. Patients with IC should remain candidates for RPC but careful pre-operative assessment is advised to exclude clinical signs favouring the diagnosis of CD. The complications associated with failure are extensive and the option of reconstructive surgery in patients with CD should be questioned.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Method
  5. Results
  6. Discussion
  7. References

Restorative proctocolectomy with ileal reservoir is the elective operation of choice for a large proportion of patients with ulcerative colitis or familial adenomatous polyposis [1,2]. Although Crohn's disease (CD) has long been considered a contraindication for restorative proctocolectomy (RPC), recent studies have suggested that patients with colonic CD with sparing of the perineum and small bowel, may be suitable candidates for restorative proctocolectomy [3,4]. Patients with indeterminate colitis (IC) comprise 10–15% of all patients undergoing RPC [5] and are identified where the pathologist is unable to distinguish between ulcerative colitis or Crohn's disease, since features of each may be present [6]. Such patients either present with fulminant colitis and have inflammation too severe to classify the pathology, or have clinical features suggestive of Crohn's disease but with some histological features suggestive of UC [5,6]. There are concerns about the role of RPC for patients with indeterminate colitis, however, the majority of studies have suggested that patients with this condition who do not develop Crohn's disease subsequently, have long-term outcomes nearly identical to patients with chronic ulcerative colitis [5]. Crohn's disease, whether it is identified after surgery for chronic ulcerative colitis or indeterminate colitis, is associated with a poor long-term outcome.

In order to determine the appropriateness of restorative proctocolectomy in patient with indeterminate colitis the study evaluated the short-term and long-term outcomes of patients undergoing restorative proctocolectomy with histologically confirmed Crohn's disease or indeterminate colitis favouring Crohn's disease and compared their outcomes with patients diagnosed with indeterminate colitis favouring ulcerative colitis thus without clinical stigmata of CD. Short and long-term functional outcomes and complication rates are presented for each patient group.

Method

  1. Top of page
  2. Abstract
  3. Introduction
  4. Method
  5. Results
  6. Discussion
  7. References

The records of all 1652 patients who underwent treatment at a tertiary referral centre between 1978 and 2003 were reviewed. Those with histological confirmation of Crohn's disease or indeterminate colitis following restorative proctocolectomy were identified from the ileal pouch database which included patients who underwent restorative proctocolectomy at St Mark's Hospital and patients who underwent primary colectomy or RPC at an outside institution. The information recorded included patient demographic characteristics, clinical and histological diagnosis, operative technique, postoperative adverse events, subsequent interventions and patient outcomes. Data on functional outcomes were gathered using a standardized questionnaire and from direct patient contact during follow-up. Data validation on the final diagnosis was performed by reviewing the histopathological reports of each patient. The study was approved by the Local Research Ethics Committee.

Study design, end points

The study population was divided into two groups (case-control design):

  • • 
    patients with indeterminate colitis or indeterminate colitis favouring ulcerative colitis (Group 1);
  • • 
    patients with Crohn's disease or indeterminate colitis favouring Crohn's disease (Group 2).

The criteria used for classification of IC or CD were identical to those adopted in an earlier study from this institution [7]. Specific features suggestive of CD included the presence of anal disease (fistula, fissure, abscess, ano rectal stenosis), colonic histopathology (granulomas, tranmural ulceration, skip lesions, rectal sparing) and disease distribution suggesting CD such as skip lesions.

The study end-points included, ileal pouch failure defined as ileal pouch excision or indefinite diversion of more than 6 months at any time during the follow-up period and pouch-related adverse events. These included fistula formation (pouch-perineal, pouch-vaginal and pouch-abdominal wall), anastomotic separation and/or stricture, pelvic sepsis, small bowel obstruction, chronic pouchitis (based on clinical endoscopic and histopathological confirmation), pouch-related bleeding, wound infections and medical complications. Functional outcomes included frequency of defecation per 24 h, nocturnal bowel movements, faecal urgency defined as the inability to defer defaecation for more than 30 min, daytime and night-time incontinence (defined by the patients themselves and classified as never, sometimes, mostly, always), the need to wear a pad at night and the need for antidiarrhoeal medication.

Statistical analysis

All pouch-related adverse events including ileal pouch-failure were regarded as time-dependent outcomes, as they can occur at any point during the follow up period and each patient has a different follow-up interval (censored). Unifactorial survival analysis based on the Cox proportional hazards regression methodology and Kaplan-Meier survival analysis was used to compare patient and procedural factors associated with pouch-related adverse events. Functional outcomes were evaluated for follow-up at 5 years after surgery or following reversal of the defunctioning ileostomy if applicable. Tables 1–3 summarize categorical variables in terms of frequencies and percentages with quantitative data summarized by means and standard deviation or median with interquartile ranges (25th to 75th percentiles). Categorical variables were compared with the Fisher exact test or chi-square tests where appropriate. Functional outcomes such as the number of bowel movements per 24 h were compared with a two-sample t-test, following logarithmic transformation of data to assume a normal distribution, maintaining an overall significance at 5%. There were too few patients to carry out a multivariate analysis. The software package ‘Statistical Package for the Social Sciences’ version 11 for Windows (SPSS, Chicago, Illinois, USA) was used.

Table 1.  Patient characteristics and operative details grouped by the final histo- pathological diagnosis. Group 1: Indeterminate colitis (IC) favouring UC (n = 26) and Group 2: patients with Crohn's disease (CD; n = 20) and indeterminate colitis favouring Crohn's disease (n = 6).
Patient characteristicsPatient groupP-value
Group 1 (n = 26)Group 2 (n = 26)
  1. Values are shown as n (%) except where otherewise labelled.

Age (years) (mean ± SD) (range)35.0 ± 12.8 (17.0–42.3)31.6 ± 11.9 (15.1–61.9)0.321
Female patients11 (42.3)18 (69.2)0.051
Comorbid disease4 (15.4)3 (11.5)0.500
Extra-intestinal manifestations5 (19.2)8 (30.8)0.337
Prior anal pathology2 (7.6) 1 (3.8)0.500
Primary ileal pouch surgery
 Preliminary colectomy18 (69.2)16 (61.5)0.550
Ileal-pouch reservoir  0.884
 W-pouch9 (34.6)9 (34.6) 
 J-pouch11 (42.3)13 (50) 
 S-pouch1 (3.8)1 (3.8) 
 Not documented5 (19.2)3 (11.5) 
Type of IPA anastomosis  0.992
 Hand-sewn13 (50.0)14 (53.8) 
 Stapled9 (34.6)8 (30.8) 
 Not documented4 (15.4)4 (15.4) 
Proximal diversion23 (88.5)23 (88.5)1.000
Dysplasia or cancer3 (11.5)2 (7.7)0.500
Table 2.  Complication rates following RPC for patients in Groups 1 and 2.
 Group 1: IC favour UCGroup 2: CD or IC favour CDHazard ratio Group 2 vs Group 195% CIP-value
Ileal pouch failure n (%)3 (11.5)15 (57.7)4.2830.972–18.8650.054
Pelvic sepsis/anastomotic leak5 (19.2)4 (15.4)0.5530.146–2.0910.383
Anastomotic stricture6 (23.1)5 (21.7)0.7380.122–1.5750.206
Pouch-related fistula5 (19.2)16 (61.5)2.6160.955–7.1710.062
Haemorrhage1 (3.8)1 (3.8)0.9140.057–14.6320.950
Pouchitis3 (11.5)4 (15.4)1.2980.261–6.4600.750
Small bowel obstruction7 (26.9)7 (26.9)0.6790.235–1.9650.475
Wound infection2 (7.6)2 (7.6)0.7100.096–5.2410.736
Other complications6 (23.1)8 (30.8)0.9920.342–2.8720.988
Table 3.  Functional outcome following RPC for patients in Groups 1 and 2 with a minimum follow-up period of 5 years.
 Group 1: IC favour UC (n = 8)Group 2: CD or IC favour CD (n = 14)P-value
Follow-up in years (median (range)) 6 (5–18) 5.5 (5–14)0.348
Stool frequency (mean (SD; range) )
 Per 24 h 7.5 (4.4; 3–15) 8.0 (4.3; 6–15)0.116
 During night 0.7 (0.8; 0–2) 2.8 (1.6; 1–5)0.024
Continence
 Urgency (mostly/always) 0 (0%) 3 (21.4%)0.273
 Incontinence (mostly/always) 1 (12.5%) 2 (14.3%)0.709
 Leakage at night 0 (0%) 3 (21.4%)0.273
 Medication 3 (37.5%) 6 (42.9%)0.584

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Method
  5. Results
  6. Discussion
  7. References

Fifty-two patients (mean age 33.2 years; SD 12.4) with the final histopathological diagnosis of Crohn's disease or indeterminate colitis were identified from a total of 1652 patients who underwent restorative proctocolectomy between 1978 and 2003. Thirty-eight (73.1%) had undergone their original restorative proctocolectomy at St Mark's Hospital and 14 (26.9%) at outside institutions. The average patient follow up was 70 months (range 2–217) with a median follow-up for Group 1 of 1.8 years (range 1–216 months) and for Group 2 of 4.7 years (range 1–203 months). The pre-operative diagnosis for restorative proctocolectomy was acute or chronic ulcerative colitis in 33 patients, indeterminate colitis in 17 and Crohn's disease in two patients. The final diagnosis was changed in 73% of patients, with a final diagnosis of Crohn's disease in 20 patients, 6 patients were classed as having indeterminate colitis favouring Crohn's disease and a further 26 as IC or IC favouring UC. Two patients initially diagnosed as Crohns had a final diagnosis of IC favouring UC. Of 17 patients with a pre-operative diagnosis of IC, three had a final diagnosis of Crohns disease, six had a final diagnosis of IC favouring CD, and eight had a final diagnosis of IC favouring UC. Of 33 patients with a pre-operative diagnosis of UC, 16 had a final diagnosis of IC favouring UC and 17 had a final diagnosis of Crohns disease.

The patient demographic characteristics, presence of comorbid conditions, extra-intestinal manifestations, pouch construction, type of anastomosis, proximal diversion and the presence of cancer in the resected specimen for patients with CD or IC are shown in Table 1.

Patients in Group 2 (CD or IC favouring CD) had a pouch failure rate of 57.5% (15/26) vs 11.5% (3/26) failure rate for patients in Group 1 (IC or IC favouring UC). Of the 15 in Group 2, one patient had an indefinite diversion via a proximal loop stoma for a contracted low-volume reservoir and 14 patients underwent pouch excision for pouch-related fistula (n = 9), faecal incontinence (n = 2), pelvic sepsis (n = 2) and pouchitis (n = 1). The reasons for pouch excision for the three patients in Group 1 were pouch-related fistula (n = 2) and faecal incontinence (n = 1).

There were four early failures within 12 months of operation and the remaining 14 failures occurred between 15 months and 14 years (median 4.2 years) after surgery. Kaplan-Meier pouch survival curves are shown by diagnosis (Fig. 1). Salvage surgery was undertaken in 15/52 patients with a 13.3% overall failure rate, 10 of these patients were in Group 1, and five patients in Group 2.

image

Figure 1. Cumulative ileal pouch survival by histopathological diagnosis. —— Group 1: Indeterminate colitis (IC) favouring UC and - - - - Group 2: patients with Crohn's disease and indeterminate colitis favouring Crohn's disease.

Download figure to PowerPoint

The associated adverse events following restorative proctocolectomy are shown in Table 2. Twenty (38.4%) patients developed a pouch-related fistula, including 16 (61.5%) of the 26 patients in Group 2 and 4 (15.4%) of 26 in Group 1. Of the patients with CD, eight of the fistulae were pouch-vaginal, seven pouch-perineal and one pouch-abdominal wall. Of the patients with IC two fistulae were pouch-perineal, one presacral and one pouch-abdominal wall. The origin of the fistula was below the anastomosis in 5 (25%) patients, at the anastomosis in 13 (65%) and above the anastomosis in 2 (10%).

Having controlled for variable patient follow up, Group 2 patients were 2.1 times more likely to develop a pouch-related fistula (P = 0.062) and 4.3 time more likely to undergo pouch excision or indefinite diversion (P = 0.054), as shown in Table 2. Kaplan Meier survival curves displaying the cumulative fistula–free survival by histopathological diagnosis are shown in Fig. 2.

image

Figure 2. Kaplan Meier survival curves displaying the cumulative fistula–free survival by histopathological diagnosis. —— Group 1; - - - - Group 2.

Download figure to PowerPoint

Information on functional outcomes following RPC was available for 22 patients, eight in Group1 and 14 in Group 2, with a follow-up period of over 5 years are shown in Table 3. No difference was evident in the 24 h bowel frequency (8 vs 7.5), faecal urgency, daytime or night time incontinence between patients in Groups 1 or 2, however, night-time frequency of defaecation was higher in patients in Group 2 (P = 0.024).

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Method
  5. Results
  6. Discussion
  7. References

Ulcerative colitis and familial adenomatous polyposis are the principal indications for restorative proctocolectomy. Crohn's disease has long been considered as a contraindication [8–10]. Some studies however, have suggested that a subgroup of patients with colonic Crohn's disease having sparing of the perineum and small bowel may be suitable candidates [3,4,10].

In the present study, patients with Crohn's disease represented 1.5% of all patients undergoing restorative proctocolectomy during the study period, a proportion which is lower than that reported by other authors, reflecting the selective criteria for RPC in the study population. This proportion is important since it reflects the accuracy of clinical and histopathological assessement [11]. The incidence of a final diagnosis of Crohn's disease was low in this study as a significant proportion of patients had undergone a prior colectomy thereby increasing the likelihood of an earlier diagnosis of Crohn's disease. The proportion of patients with CD in reported studies is as high as 13%[9]. This may result in a distortion of the percentage of patients diagnosed with IC. Indeterminate colitis is not a diagnosis in itself but is a statement by the pathologist that there are insufficient or conflicting features to decide between UC on one hand and CD on the other.

The average patient follow up was 70 months with a failure rate and pouch-related fistula rate for Group 2 of 57.7% compared with 61.5% for Group 1. Various authors have reported diametrically opposing views and outcomes of RPC in patients with known Crohn's disease and indeterminate colitis. In the study by Panis et al. [3], 31 patients with Crohn's disease without evidence of anoperineal or small-bowel disease, were compared with 71 ulcerative colitis patients who also underwent RPC during the same period at a mean follow-up 59 months. No significant differences were observed between patients with CD and ulcerative colitis in the postoperative complication rate. At 5-year follow-up, there were no significant differences between the two groups in stool frequency, continence, need for protective pads, and sexual activity. The same authors [4] subsequently reported the longer term results of 41 patients who underwent RPC with a pre-operative diagnosis of colorectal Crohn's disease between 1985 and 1998. The pouch-related complications and excision rates were 35 and 10%, respectively. None of the patients had a past history of an anal lesion or evidence of small-bowel involvement. These data raise the question as to whether some of the patients would have been classified by other pathologists as having IC possibly inclining towards UC. In contrast, Grobler et al. [12] and Keighley et al.13] reported higher complication rates in patients with clinical and histopathological features suggestive of CD but with acceptable functional results. Mylonakis et al. [14] in a study of 23 patients with CD and 35 patients with ileoproctostomy (mean follow-up 10.2 years) reported 47.8% pouch excisions vs 8% rectal excisions, results which are in line with the present study.

Patients with indeterminate colitis present a difficulty in case selection. This ‘diagnostic’ category is variable and is the result of histopathological uncertaintly where IC is redefined by additional clinical factors with patients inclining more to CD on the one hand and UC on the other. The results of the present study showed that patients with indeterminate colitis had outcomes similar to those of ulcerative colitis. Conversely, patients subsequently found to have clinical features suggestive of CD had complication rates similar to patients with CD. In a study of 1437 patients with chronic ulcerative colitis and 82 patients with indeterminate colitis undergoing RPC between 1981 and 1995 at 10 years, patients with indeterminate colitis had significantly more episodes of pelvic sepsis (17% indeterminate colitis vs 7% ulcerative colitis), pouch fistula (31 vs 9%), and pouch failure (27 vs 11%) [15]. During follow-up, 15% of patients with indeterminate colitis, had their original diagnosis changed to Crohn's disease. When the outcomes of these patients newly diagnosed with Crohn's disease were considered separately, the rate of complications for the remaining patients with indeterminate colitis was identical to that of patients with chronic ulcerative colitis.

Similar results were reported in a study of 115 patients with indeterminate colitis [5]. Functional outcomes, the incidence of anastomotic complications and major pouch fistulae were similar in UC and indeterminate colitic patients. Although IC patients were more likely to develop minor perineal fistula, pelvic abscess, and Crohn's disease, the rate of pouch failure was 3.4%, identical to that of UC patients. There was no clinically significant difference in quality of life, or satisfaction with RPC.

The results of a study of 71 patients with indeterminate colitis compared with 1232 patients with chronic ulcerative colitis were similar [16]. At a mean follow-up of 5-years, failure rates appeared to occur more frequently in patients with indeterminate colitis (19%), than in patients with chronic ulcerative colitis (8%). However, the great majority of indeterminate colitis patients (>80%) had long-term functional results identical to those of patients with chronic ulcerative colitis. In a smaller study, pouch-related complications, pouch failure, and discovery of underlying Crohn's disease occurred in a significant number of patients with indeterminate colitis [17].

The present study shows that patients with indeterminate colitis who do not show clinical features, especially anal, of CD and who did not develop Crohn's disease, subsequently experienced a long-term outcome nearly identical to patients with chronic ulcerative colitis. Crohn's disease, whether it is recognized before or after surgery, is associated with a poor long-term outcome. In patients with a functioning reservoir functional outcomes for those with CD or IC were similar. Thus patients with IC should remain candidates for RPC but careful pre-operative assessment is advised to exclude clinical features inclining towards the diagnosis of CD.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Method
  5. Results
  6. Discussion
  7. References