International Journal of Colorectal Disease

, Volume 22, Issue 9, pp 1061–1069

Surgical predictors of recurrence of Crohn’s disease after ileocolonic resection

Authors

    • Clinica Chirurgica I, Dipartimento di Scienze Chirurgiche e GastroenterologichePoliclinico Universitario, Università di Padova
  • Cesare Ruffolo
    • Clinica Chirurgica I, Dipartimento di Scienze Chirurgiche e GastroenterologichePoliclinico Universitario, Università di Padova
  • Eugenia Bertin
    • Clinica Chirurgica I, Dipartimento di Scienze Chirurgiche e GastroenterologichePoliclinico Universitario, Università di Padova
  • Lino Polese
    • Clinica Chirurgica I, Dipartimento di Scienze Chirurgiche e GastroenterologichePoliclinico Universitario, Università di Padova
  • Teresa Filosa
    • Clinica Chirurgica I, Dipartimento di Scienze Chirurgiche e GastroenterologichePoliclinico Universitario, Università di Padova
  • Daniela Prando
    • Clinica Chirurgica I, Dipartimento di Scienze Chirurgiche e GastroenterologichePoliclinico Universitario, Università di Padova
  • Duilio Pagano
    • Clinica Chirurgica I, Dipartimento di Scienze Chirurgiche e GastroenterologichePoliclinico Universitario, Università di Padova
  • Lorenzo Norberto
    • Clinica Chirurgica I, Dipartimento di Scienze Chirurgiche e GastroenterologichePoliclinico Universitario, Università di Padova
  • Mauro Frego
    • Clinica Chirurgica I, Dipartimento di Scienze Chirurgiche e GastroenterologichePoliclinico Universitario, Università di Padova
  • Davide F. D’Amico
    • Clinica Chirurgica I, Dipartimento di Scienze Chirurgiche e GastroenterologichePoliclinico Universitario, Università di Padova
  • Imerio Angriman
    • Clinica Chirurgica I, Dipartimento di Scienze Chirurgiche e GastroenterologichePoliclinico Universitario, Università di Padova
Original Article

DOI: 10.1007/s00384-007-0329-4

Cite this article as:
Scarpa, M., Ruffolo, C., Bertin, E. et al. Int J Colorectal Dis (2007) 22: 1061. doi:10.1007/s00384-007-0329-4

Abstract

Background/aims

Anastomotic recurrence after bowel resection is a major problem in Crohn’s disease (CD) surgery. The aims of this retrospective study are to assess the role of anastomotic configuration, the type of suture and the type of surgical approach (laparoscopy-assisted vs laparotomy) in CD recurrence. Secondary end points were to identify any possible predictor that would help the selection of patients for medical prophylaxis.

Materials and methods

In this retrospective study, we enrolled 141 consecutive patients who had undergone ileocolonic resection for CD. Univariate actuarial analysis was performed according to demographic, clinical and surgical predictors. Variables that resulted to be significant at the univariate analysis were included in two multivariate Cox proportional hazards models that analyzed symptomatic and surgical recurrence, respectively.

Results

In the long-term, handsewn side-to-side anastomosis reported a significantly lower surgical recurrence rate than stapled end-to-side (p < 0.05). At multivariate analysis, anastomosis type, surgical and intestinal complications (p < 0.01) and age at CD onset (p < 0.05) resulted to be significant predictors for re-operation for CD recurrence. Multivariate analysis showed that surgical complication was also a significant predictor of symptomatic recurrence.

Conclusions

Side-to-side anastomosis configuration seems to delay re-operation and can be assumed as the standard configuration in ileocolonic anastomosis in CD. Post-operative complications and young age at disease onset might be a signal of aggressive CD that may warrant prophylactic pharmacological therapy.

Keywords

Crohn’s diseaseRecurrenceStapled side-to-side anastomosisHandsewn side-to-side anastomosis

Abbreviations

CD

Crohn’s disease

5-ASA

5-aminosalicylic acid

Pts

patients

Introduction

Many patients, after a bowel resection for Crohn’s disease (CD), will experience a recurrence at the site of the anastomosis that may eventually lead to further operations [1, 2]. Several demographic and pathological factors have been investigated for their supposed influence of recurrence of CD [3]. Gender, family history, symptomatic status, presence of granulomas, “obstructing” vs “fistulising” CD, length of surgical margins and presence of microscopic disease at the surgical margin, site of the disease and number of sites involved, type of operation, and number of anastomosis did not show any definitive clue to be implicated in recurrence [35]. Smoking seems to be the only assessed environmental risk factor for recurrence after surgery [6].

Medical therapy for the prevention of CD recurrence has been thoroughly investigated. The prophylactic treatment with full dose 5-ASA after resection reduces Crohn’s recurrence rates [4, 5, 7] but the benefits seem to be confined to ileal CD [8]. The post-operative use of 6-mercaptopurines and steroids showed scarce or no improvement on clinical recurrence rates whilst nitroimidazole antibiotics and azathioprine seemed to be effective at the price of potentially important side effects or of long-term therapy [911]. An accurate selection according to the presence of risk factors and to early endoscopic investigations of the patient candidate to these prophylactic protocols is therefore necessary [9, 10].

The assessment of the role of surgical therapy in minimising the post-operative recurrence still lacks proper randomised trials. The role of the type of anastomosis is still debated and positive promises of the minimally invasive approach have not been studied enough yet. In fact, laparoscopic ileocolonic resection seemed to lead to reduced recurrence rates due to its low inflammatory activation; but this data needs further long-term confirmations [12]. On the other hand, whilst some authors denied any influence of the type of the anastomosis [5, 7, 13], some other authors claim significantly better results of stapled side-to-side anastomosis after ileocolonic resection compared to end-to-end handsewn anastomosis [1417]. In this last comparison, both suture technique and anastomotic configuration were changed so it was not possible to identify which was the main factor that reduced recurrence after CD surgery. For this reason, in 2002, we compared outcome and recurrence rates of patients who had stapled side-to-side ileocolonic anastomosis to those of patients who had stapled end-to-side or handsewn side-to-side anastomosis and we evidenced that the configuration of the ileocolonic anastomosis may play a role in the prevention of CD recurrence [18]. However, this study included a small sample of side-to-side stapled anastomosis size so its results could not be regarded as conclusive.

The main aim of this retrospective study is to verify the results we obtained in 2002 with a larger and more adequate sample size. Secondary end points were to identify any possible predictor that would help the selection of patients for medical prophylaxis and to assess the possible role of laparoscopy in reducing post-operative CD recurrence.

Materials and methods

Study design

Records of all the 141 consecutive patients who underwent ileocolonic resection for CD in our institute from 1997 to 2005 and details of the outpatient’s clinic follow-up were reviewed. In 2006, 97 patients who had not attended to our outpatient’s clinic for more than 6 months were contacted directly and agreed to answer to a telephone interview. The interview was focused on the onset of recurrent symptom, re-operation and therapy. Patients were asked for the presence of abdominal symptoms, fever and extra-intestinal manifestations, for their bowel habits, weight, number of medical visits for CD, medical therapy, hospital admitting and re-operation with the respective dates. Of these patients, 63 also agreed to come to the clinic for a complete checkup and an assessment of the Crohn’s disease activity index (CDAI).

Patients were enrolled in the study if they had an ileocolonic anastomosis for Crohn’s disease. We also included patients with recurrent ileocolonic disease because literature data showed that there is no difference in recurrence rate after the second resection [4, 19, 20]. We excluded from this study patients who also presented other bowel diseases associated to Crohn’s disease such as colon cancer and those who had more than one bowel anastomosis during a single operation or who presented an involvement of the colon that implied more than a right hemicolectomy (i.e. left hemicolectomy or sub-total colectomy). Patients who (also) had stricturoplasty, in whom the disease persisted, were excluded. Therefore, we considered any further Crohn’s disease manifestation as a “recurrence” and not as “persistence”. No pre-operative criteria were established to choose the type of anastomosis other than the preference of every single surgeon. AT performed stapled end-to-side anastomosis, DFDA and MF performed handsewn side-to-side anastomosis and IA performed stapled side-to-side anastomosis. All four of them were consultant surgeons fully trained in colorectal and inflammatory bowel disease surgery. On the contrary, patients who had laparoscopy-assisted ileocolonic resection were selected pre-operatively according to their surgical history and the presence of complication that would have suggested an easier open approach.

In this retrospective setting, we assumed patients having a clinical recurrence when CD bowel manifestations, confirmed by endoscopy and/or small bowel series, were so severe that a significant increase in medical therapy (switch from 5-ASA to steroids or immunosuppressive drugs) was necessary. Surgical anastomotic recurrence was defined as a re-operation. Re-operation was only considered as further bowel resections that involved the previous ileocolonic anastomosis with histological confirmation of the presence of active CD in the surgical specimen. We also considered as surgical anastomotic recurrence those patients submitted to further ileocolonic resection within the first post-operative month provided that Crohn’s recurrence was documented by the histological examination on the resected specimen [5, 14, 21].

Patients

From January 1997 to June 2005, 141 patients have undergone ileocolonic resection for CD in our institute. Their median age at operation was 36 years (range 14–74) and 89 of them were males. The disease duration before the operation was 96 months (range 1–384). The indications for resection were: CD of the terminal ileum refractory to medical therapy or with critical stenosis in 73 patients, recurrent CD of the terminal ileum in 42 patients, CD of the terminal ileum complicated by fistula or abscess in 20 patients and CD of the terminal ileum involving the right colon in 6 patients. Ileocolonic resection was performed with open technique in 122 patients and with laparoscopy assistance in 19 patients. Patients were grouped according to the anastomosis type: 56 of them had stapled side-to-side anastomosis, 37 had stapled end-to-side anastomosis and 48 had handsewn side-to-side anastomosis. The characteristics of these groups are summarised in Table 1. All the patients received oral mesalazine as prophylactic therapy at a dose of 2.4 g/day at their discharge. The median follow-up of the patients was 39 months (range 6–105).
Table 1

Patients characteristics

 

Stapled side-to-side

Stapled end-to-side

Handsewn side-to-side

Number of patients (pts)

56

37

48

Sex (males)

32 (57%)

26 (70%)

30 (62%)

Age at operation (years)

36 (19–73)

39 (18–63)

34 (14–74)

Recurrent ileocolonic disease (pts)

11 (20%)

16 (43%)

15 (31%)

Mean follow-up (months)a

25 (6–76)

67 (28–96)

49 (6–105)

aThe comparison with ANOVA followed by LSD test and with Fisher exact test demonstrated a significant difference among the three groups (p < 0.01).

Surgical technique

The ileocolonic resection was performed removing all grossly involved bowels through a standard mid-line laparotomy or with laparoscopy assistance. The effectiveness of the macroscopical radicality was assessed by histological analysis, which showed that the histological disease activity at the resection margin was absent or very mild. In the laparoscopy-assisted ileocolonic resection, a 3 trocar approach was used (sub-umbilical, 10 mm; left iliac fossa, 10 mm; supra-pubic, 5 mm). The distal ileum and the right colon were fully mobilised and exteriorised by a 4–6 cm vertical incision through the umbilicus. In case of enterosigmoid fistula or large inflammatory mass, a small Pfannenstiel incision (8 cm) was used instead of the trans-umbilical incision [22]. Vascular ligation, bowel division and the anastomosis were performed extracorporeally. Side-to-side anastomosis was constructed with two 80-mm linear staple cutter (GIA80, US Surgical, Norwalk, CT, USA) as described for cancer surgery by Reynolds and Enker [23] and Meagher and Wolff [24] and for Crohn’s disease by Yamamoto and Keighley [25]. End-to-side anastomosis was performed using a circular stapler (PCEEA31 or PCEEA28 US Surgical, Norwalk, CT, USA), depending on the size of the bowel, and a TA55 to close the colonic stump [26]. The sutured side-to-side anastomosis was performed layer-by-layer: the inner layer (mucosal) was anastomosed with a running suture of 3-0 Vicryl, (Ethicon, Somerville, NJ, USA) and the outer layer (seromuscular) was sewn with a running suture of 3-0 Ti-Cron.

Statistical analysis

The statistical analysis was performed using both Microsoft Excel and Statsoft Statistica 7.1 software. Continuous data were expressed as median (range). The post-operative outcome was evaluated considering the duration of operation, the first bowel movement after operation, the post-operative hospital stay, the post-operative surgical complications (bleeding, anastomotic leakage and obstruction), the post-operative gastroenterological complications (diarrhoea or per rectal bleeding) and re-operation rate within the first 30 days after the operation. The statistical analysis of these data was performed using ANOVA followed by the least significant difference (LSD) post hoc test for continuous variables. Dichotomous variables were analysed with Fisher exact test.

Actuarial recurrence analysis included as independent variables: gender, age at operation, CD duration, age at CD onset, recurrent CD, CD phenotype, laparoscopy/laparotomy approach, anastomosis type, duration of the operation, duration of the post-operative hospital stay, day of first bowel movement, post-operative surgical and intestinal complications and medical therapy. Symptomatic recurrence-free survival was calculated using actuarial (Kaplan–Meier) analysis with follow-up time (time at risk) beginning at initial surgery and ending at the first recurrence of symptoms, as defined above, or at last available follow-up, whichever came first. Surgical recurrence-free survival was calculated in the same way with the time at risk ending at first re-operation or at last available follow-up, whichever came first. Data were considered as complete when patients had a clinical or surgical evidence of anastomotic recurrence according to the above definitions. Cumulative recurrence rates were compared using log rank test or Cox F test where appropriate.

Multiple variable Cox proportional hazards models were used to determine independent predictors of symptomatic and surgical recurrence. All the variables that resulted to be significant at the univariate analysis were included in two models that analyzed symptomatic and surgical recurrence, respectively.

A level of p < 0.05 was considered significant in all the analyses and Bonferroni adjustment was used where appropriate.

Results

The main parameters of the post-operative outcome did not show any statistically significant difference between the three groups as illustrated in Table 2. Only follow-up length was significantly different among anastomosis groups: it was 25 months (range 6–76) for the stapled side-to-side group, 67 months (range 28–96) for the stapled end-to-side group and 49 months (range 6–105) for the handsewn group (p < 0.05). In fact, the mean duration of operation, the first bowel movement, the mean post-operative hospital stay and the intestinal complications rate were similar in the three groups of patients submitted to ileocolonic resection with the different kinds of anastomosis. Even if the surgical complications and the early re-operation rates were slightly higher in the stapled groups, the difference did not reach statistical significance. In fact, five patients who had stapled side-to-side or end-to-side anastomosis presented with early obstruction and were submitted to re-operation within the first post-operative month. The histological report confirmed the presence of active CD in the specimen of all these cases. In the group of patients who had a stapled side-to-side anastomosis, a patient with intra-abdominal bleeding underwent to a further laparotomy for haemostasis. In the group of handsewn anastomosis, three patients presented, respectively, with obstruction, rectal bleeding and anastomotic leak but all of them were managed conservatively.
Table 2

Post-operative outcome

 

Stapled side-to-side

Stapled end-to-side

Handsewn side-to-side

Duration of operation (min)

180 (75–390)

195 (100–500)

180 (90–600)

First bowel movement (days)

3.5 (2–8)

3.0 (2–6)

4.0 (4–9)

Post-operative hospital staying (days)

9 (6–18)

9 (6–20)

9 (4–15)

Intestinal complications (pts)

6 (11%)

4 (11%)

5 (10%)

Surgical complications (pts)

3 (5%)

3 (8%)

3 (6%)

Early re-operation (pts)

3 (5%)

3 (8%)

0 (0%)

Histology positive for CD

2

3

NA

The comparison with ANOVA followed by LSD test and with Fisher exact test did not show any significant difference among the three groups.

In our whole series, the symptoms recurred with a 10% rate at 1 year and 22% at 5 years whilst the re-operation recurrence rate was 5% after 1 year and 10% at 5 years. A clinical recurrence was referred by 7 (12%) patients in the stapled side-to-side group medially after 6.5 months (range 1–36), by 11 (30%) patients in the stapled end-to-side group after 22.5 months (range 1–78) and by 9 (19%) patients in the handsewn group after 24 months (range 1–72). The symptomatic recurrence-free cumulative rates were 88%, 89% and 93% after 12 months and 76%, 76% and 82% after 60 months, respectively. At the moment of the study, six patients in the group who underwent stapled side-to-side anastomosis were receiving azathioprine and one steroids (two of them were also receiving steroids). In the stapled end-to-side group, three patients were receiving azathioprine and steroids, one only steroids and one infliximab. In the handsewn group, one patient was receiving steroids and another one was receiving infliximab. No statistical difference was demonstrated among the three groups as showed in Fig. 1.
https://static-content.springer.com/image/art%3A10.1007%2Fs00384-007-0329-4/MediaObjects/384_2007_329_Fig1_HTML.gif
Fig. 1

Kaplan–Meier curve demonstrating the percentage of patients remaining free of symptoms of anastomotic recurrence of CD according to the anastomosis type. The cumulative re-operation rates were not significantly different among the three groups

In the stapled side-to-side anastomosis group, 4 (7%) patients presented an anastomotic recurrence treated surgically medially 13 months (range 1–24) after the first operation. In addition to the 3 patients who had an early recurrence as described above, 5 other patients in the stapled end-to-side anastomosis group had an anastomotic CD recurrence (21%) and needed a further resection meanly 14 months (range 1–80) after the first operation. Two (4%) patients in the handsewn group were submitted to further bowel resection for CD recurrence and the operations were performed 52.5 months (range 25–80) after the first resection. Histological analysis confirmed the presence of active CD recurrence in all the resected intestinal specimens from the re-operation. The cumulative re-operation-free surviving rates after 12 months were 96% for stapled side-to-side anastomosis, 89% for stapled end-to-side anastomosis and 100% for handsewn side-to-side anastomosis. The same rates after 60 months were 91%, 84% and 94%, respectively. Log rank test revealed a statistically significant difference in the comparison between handsewn and stapled end-to-side group (p < 0.05). At the analysis with the Cox F test, more sensible than log rank test for short follow-up, the differences between stapled side-to-side group and stapled end-to-side and between handsewn and stapled end-to-side were statistically significant (p < 0.05). The three re-operation rates are shown in Fig. 2.
https://static-content.springer.com/image/art%3A10.1007%2Fs00384-007-0329-4/MediaObjects/384_2007_329_Fig2_HTML.gif
Fig. 2

Kaplan–Meier curve demonstrating the percentage of patients remaining free of re-operation for anastomotic recurrence of CD according to the anastomosis type. In the short-term, the cumulative re-operation rates were significantly lower in the side-to-side group than in the end-to-side group (p = 0.05) whilst in the long-term, handsewn side-to-side was superior than stapled end-to-side (p = 0.05)

Univariate analysis of the other risk factors showed that gender, age at operation, recurrent or first operation CD, laparoscopy or laparotomy approach, indication for surgery, duration of the operation, duration of the post-operative hospital stay, day of first bowel movement and medical therapy could not be considered as predictors of symptomatic or surgical recurrence. On the contrary, patients who had a CD onset in younger age (<20 years) reported a lower symptom-free and operation-free post-operative survival than patients who had CD onset in older age (p < 0.05). Patients who were operated on for obstructing CD reported a higher cumulative rate of symptomatic recurrence than patients with fistulising CD (p = 0.02). Patients with short CD duration (<2 years) before the resection reported a significantly lower rate of surgical and clinical recurrence (p < 0.05). Patients who had a post-operative course complicated by diarrhoea or per rectal bleeding had a higher cumulative rate of re-operation (p = 0.01). Finally, patients who had post-operative surgical complications reported a significantly higher rate of surgical and clinical recurrence (p < 0.01).

Multiple variable Cox proportional hazards models were created with the variables that resulted to be significant at the univariate analysis. In the model that analysed the symptomatic recurrence, we included surgical complications, CD duration, age at CD onset and CD “phenotype” (fistulising vs obstructing). In this model, only the presence of surgical complications turned out to be an independent predictor of symptomatic recurrence (p < 0.01). On the other hand, the model that analyzed the significant risk factors for surgical recurrence, included post-operative gastroenterological and surgical complications, CD duration, anastomosis type and age at CD onset. In this model, anastomosis type, surgical complications and post-operative gastroenterological complications resulted to be strong independent predictors of surgical recurrence (p < 0.01). Furthermore, age at CD onset showed to be a predictor of recurrence that needed surgical treatment (p = 0.02). The details of the multivariate analysis are shown in Table 3.
Table 3

Significant predictors at the multivariate Cox proportional hazards models analysis

 

Cox proportional hazard model

12 months (%)

60 months (%)

Wald statistic

p

Cumulative symptomatic recurrence rate

Surgical complications

  

11.171

<0.001

 Yes (9 pts)

40

100

  

 No (132 pts)

7

10

  

Cumulative surgical recurrence rate

Anastomosis type

  

7.253

0.007

 Stapled side-to-side (56 pts)

4

11

  

 Handsewn side-to-side (48 pts)

0

6

  

 Stapled end-to-side (37 pts)

11

16

  

Intestinal complications

  

6.892

0.008

 Yes (15 pts)

17

27

  

 No (126 pts)

3

9

  

Surgical complications

  

15.545

<0.001

 Yes (9 pts)

44

   

 No (132 pts)

2

7

  

Age at CD onset

  

5.869

0.015

 <20 years (21 pts)

5

23

  

 21–40 years (51 pts)

0

0

  

 >40 years (12 pts)

0

0

  

Discussion

Post-operative recurrence after bowel resection is a major problem in CD management, which leads to further bowel resection 11–32% of patients after 5 years and 46–55% after 20 years, according to the different series [3, 5, 27]. In our series, the symptoms recurred with a 10% rate at 1 year and 23% at 5 years whilst the re-operation recurrence rate was 4% at 1 year and 10% at 5 years. Slightly higher cumulative symptom and re-operation-free survival rates compared to those reported by Yamamoto [3] are probably due to very strict criteria for the definition of clinical and surgical recurrence. Although Rutgeert et al. found a histological recurrence rate, as proven by biopsies taken by colonoscopy from the anastomosis, of about 30% after 3 to 6 months after ileocecal resection and a similar rate of macroscopic changes within the first post-operative year [28], endoscopic rates of up to 75% within the first post-operative year have been described by several authors [5]. Furthermore, early anastomotic strictures were documented by barium enema by Hashemi et al. [14] and very early re-operation for recurrence were reported in the series of Borley et al. [21]. For all these reasons, we also decided to consider patients who submitted to further ileocolonic resection within the first post-operative month as surgical anastomotic recurrence, provided that Crohn’s recurrence was documented in the histology of the further intestinal specimen.

Several demographic, operative and pathological factors have been investigated for their supposed influence on CD recurrence, and the most significant risk factor seems to be smoking [3, 5]. The type of anastomosis entered significantly into the debate about post-operative recurrence in 1998 when stapled side-to-side anastomosis resulted to have lower re-operation rates compared to handsewn end-to-end anastomosis [14]. In further studies, stapled side-to-side anastomosis confirmed its lower recurrence rate because of its wide lumen that contributes to the prevention of early stenosis, subsequent faecal stasis and secondary ischemia [1517]. However, all these retrospective studies compared stapled side-to-side anastomosis to handsewn end-to-end anastomosis: two factors, suture technique and anastomotic configuration with just one equation. The consequent step in the investigation was to understand which factor was the real protagonist in the delay of the recurrence: stapled suture or side-to-side anastomotic configuration. In 2002, we analysed the follow-up of all the consecutive patients who had undergone ileocolonic resection since 1997 with different ileocolonic anastomosis: stapled side-to-side, handsewn side-to-side or stapled end-to-side. It turned out that stapled side-to-side and handsewn side-to-side anastomosis were associated with a significantly lower re-operation rate compared to stapled end-to-side anastomosis, but symptoms recurred with similar frequency in the three groups [18].

The aim of this study was to further evaluate the observations we had reported in 2002 using a larger patient cohort and a more adequate statistical analysis. Firstly, all the three types of anastomosis were confirmed to be equally safe in terms of complications and of early post-operative outcome, as reported in the literature [18, 29, 30]. Then, multivariate analysis demonstrated that anastomosis type is a strong independent predictor of surgical recurrence. In fact, univariate analysis with log rank test confirmed that handsewn side-to-side anastomosis had lower surgical recurrence cumulative rates than stapled end-to-side. The stapled side-to-side anastomosis group showed a significantly shorter follow-up; when we used a more appropriate short-term analysis, this group was demonstrated to have significantly lower cumulative re-operation rates than end-to-side and similar to handsewn side-to-side group. Even in our previous study, we observed longer symptom-free intervals in stapled side-to-side compared to the stapled end-to-side anastomosis group. In the present series, similar cumulative symptomatic recurrence rates were reported by all three groups. Now, we can affirm that side-to-side configuration of anastomosis has clearly no influence on the natural history of CD but possibly the width of its lumen may help to prolong the re-operation-free survival. This result attributes the low anastomotic recurrence rate of stapled side-to-side anastomosis reported by several authors [1417] to the wide configuration independently from the type of suture. In fact, the type of suture was not proven to be a predictor for both symptomatic and surgical recurrence. Stapled suture is probably helpful in preventing post-operative sepsis of the anastomosis but it cannot be considered essential or even less sufficient to prevent the anastomotic recurrence of CD.

The surgical access, laparoscopy-assisted vs conventional laparotomy, did not result to be as relevant as well, for the following development of recurrence as reported by Lowney et al. [31]. Contrary to what was described by Bergamaschi et al. [12], the recurrence rate was not lower than that of the open technique probably because of a conserved immune function that does not slow down the inflammatory process [32]. The relatively high incidence of recurrence in the early post-operative period observed in our series seems to support this hypothesis.

The analysis of the possible predictors of recurrence that might be used in planning a prophylactic pharmaceutical therapy showed that among the perioperative risk factors, only the presence of surgical complications resulted to be a significant predictor of both surgical and symptomatic recurrence. In spite of the small sample size of the group of patients who suffered post-operative haemorrhage, anastomotic leakage or obstruction, the strength of the statistical association suggests that surgical complications may be considered as signals of aggressive CD with high probability of early recurrence. The same role of “clue” of aggressive CD with high probability of early surgical recurrence may be attributed to the post-operative gastroenterological complications. In fact, patients who had a post-operative course with intestinal complications such as diarrhoea or per rectal bleeding had a higher cumulative rate of re-operation.

The multivariate analysis confirmed that a young age at CD onset may be a predictor of recurrence that needed surgical treatment. Even if this issue is still debated [3], there are authoritative authors who report similar findings [33]. A more aggressive pattern of CD with early disease onset is consistent with the latest theories about CD pathogenesis due to a deficiency of the expression of mucosal defensins [34].

A limit of this study was that, in a retrospective setting, clinical recurrence could not be certainly attributed to an anastomotic recurrence because the symptoms suggesting recurrent disease could also be caused by CD at sites of the gastrointestinal tract far away from the previous anastomosis. A further limit is the different median follow-up duration of the three anastomosis type groups: this difference reflected the different periods when the diverse techniques were used by the different surgeons. The problem of the differentiation between “recurrence” and “persistence” of CD after ileocolonic resection was solved by assessing the effectiveness of our macroscopical radicality at histological level, excluding the persistence of active disease in the bowel, such as in the case of stricturoplasty, and confirming the histological presence of active CD in the resected specimen after re-operation.

In conclusion, handsewn side-to-side anastomosis showed a significantly lower surgical recurrence rate than stapled end-to-side anastomosis and, in the short-term, this result was similar for stapled side-to-side anastomosis. Side-to-side configuration seems to delay re-operation probably by reducing obstruction symptoms. In our opinion, side-to-side anastomosis might be adopted as the standard anastomosis for ileocolonic resection for CD, whichever suture type is chosen. No other surgical risk factors, such as the type of suture or surgical access seems to have any relevance as predictor of recurrence. Post-operative complications and young age at disease onset may be a signal of aggressive CD that should warrant prophylactic therapy with azathioprine or antibiotics despite their potential side effects.

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© Springer-Verlag 2007