Survival and Recurrence Period
The mean duration of the period between the first and second surgery was not significantly different between the groups, whereas the mean duration time to clinical recurrence was significantly different (SC group, 67 ± 32 months; TC group, 92 ± 42 months; P = 0.008; Table 2). Among the 54 patients who had ≥2 involved colonic segments (multisegments), the mean duration time to surgical and clinical recurrence was significantly shorter in the SC group compared with the TC group (surgical recurrence, 60 ± 33 vs 91 ± 42 months, P = 0.02; clinical recurrence, 40 ± 21 vs 83 ± 42 months, P = 0.002).
Among 116 patients with Crohn colitis, 45 patients in the TC group exhibited a significantly higher CRFS compared with 71 patients in the SC group (5-year CRFS: 82.0% ± 5.8% vs 66.8% ± 5.7%, P = 0.001). By contrast, the SRFS was similar between the 2 groups (Figure 2). Among the 54 patients with multisegments involvement, the TC group showed a significantly higher 5-year CRFS and 5-year SRFS compared with the SC group (5-year CRFS: 82.0% ± 5.8% vs 22.2% ± 13.9%, P = 0.001; 5-year SRFS: 88.1% ± 5.0% vs 44.4% ± 16.6%, P = 0.001; Figure 2). When we divided the SC group into patients who underwent single-segmental resection (SSR) or multi-segmental resection (MSR), the survival outcomes were significantly different between SSR and MSR and between MSR and TC (SSR vs MSR vs TC; 5-year SRFS: 73.6% ± 16.6% vs 57.5% ± 14.6% vs 88.1% ± 5.0%, P = 0.001 and 5-year CRFS: 73.3% ± 5.9% vs 38.5% ± 13.5% vs 82.0% ± 5.8%, P = 0.001; Figure 2).
In a univariate analysis of our study subjects, SRFS was associated with a preoperative history of perianal disease, perianal disease after the first operation, the extent of involvement, and the extent of the operation. In subsequent multivariate analysis that included these variables, a history of perianal disease after the first operation, rectal involvement, and SC were found to be risk factors for SRFS (Table 3). The variables that correlated with CRFS by univariate analysis were perianal disease after the first operation, a family history of CD, disease behavior for an operation, multiple involvements, the extent of operation, and recovery of hemoglobin levels. By multivariate analysis, CRFS was associated with penetrating behavior and the operative extent of SC (Table 3).
In univariate analysis of 54 patients with multisegment involvement, SRFS was associated with a family history of CD, the extent of operation, and recovery of hemoglobin levels. By multivariate analysis of the 54 patients, SC (hazard ratio [HR] = 4.637, 95% confidence interval [CI] = 1.387–15.509, P = 0.013) and recovery of hemoglobin levels (HR = 0.296, 95% CI = 0.095–0.923, P = 0.036) were risk factors for SRFS. Variables that correlated with CRFS by univariate analysis for the 54 patients with multisegment involvement were perianal disease after the first operation, disease behavior for operation, multiple involvements, the extent of operation, and recovery of hemoglobin levels. Multivariate analysis showed that SC was a risk factor for CRFS (HR = 32.407, 95% CI = 2.873–365.583, P = 0.005) (Supplement Table 1, http://links.lww.com/MD/A1000).
No types of medications except anti-TNF agent that were administered after surgery affected CRFS or SFRS. Subgroup analysis of 39 patients who were administered anti-TNF agents after the first operation revealed that there was a significant difference in the CRFS, but not the SRFS between the SC and TC groups (SC vs TC: 5-year SRFS; 87.1% ± 8.6% vs 90.7% ± 6.3%, P = 0.23 and 5-year CRFS; 64.7% ± 11.6% vs 76.4% ± 9.3%, P = 0.024) (Supplement Figure 1, http://links.lww.com/MD/A1000). In the subgroup analysis of 77 patients who did not receive anti-TNF agents after the first operation, the survival outcomes were similar to those of anti-TNF-treated patients (SC vs TC: 5-year SRFS; 86.1% ± 4.9% vs 85.6% ± 7.8%, P = 0.29 and 5-year CRFS; 65.6% ± 6.6% vs 82.4% ± 8.0%, P = 0.003). In subgroup analyses of 54 patients with multisegment involvement, the TC group showed a significantly higher 5-year CRFS and 5-year SRFS compared with the SC group, regardless of anti-TNF agents (Supplement Figure 1, http://links.lww.com/MD/A1000).
Although the 116 Crohn colitis patients treated at our institution during our present study period underwent various types of surgery, we classified these patients into 2 groups depending upon the surgical strategy. We found that the clinical and surgical recurrence rates increased after segmental resection of colon, which was similar to other studies.7,17 Furthermore, we found that the SC group could be defined as an independent risk factor for SRFS and CRFS. Especially, when disease was detected in multisegments, the differences in SRFS and CRFS became severe between the SC and TC groups.
In a comparison of the SC and TC groups, the demographics of these 2 groups of patients differed significantly for sex, duration between the time of diagnosis and the first operation, and segments involved. Although several studies have shown an increased rate of recurrence for females,11,18 we found in our present study that sex had no effect on the recurrence of Crohn colitis (5-year SRFS: female vs male, 82.7% ± 6.0% vs 88.4% ± 3.9%, P = 0.76), which was in accord with the findings of other studies.12,19 Considering the natural history of CD,20 a longer duration between the time of diagnosis and the first operation in the TC group appeared to affect the extent of disease, disease behavior, and the choice of a surgical treatment.
Although the extent of colonic disease affected the choice of surgical treatment, our present findings suggest that TC in patients with multisegment involvement had a lower risk of causing clinical or surgical recurrence and was associated with a prolonged time to clinical and surgical recurrence. Patients in the TC group exhibited a lower crude recurrence rate (10.9%), compared with previous reports that described a 44% crude recurrence risk after resection in Crohn colitis patients.12,21,22 Previous studies have indicated that the recurrence rate for SC varies from 33% to 62%, and that the rate for TC varies from 4% to 79.9%.7,8,11,14,23 In our present study, the 5-year SFRS that we observed after SC and TC was 88.0% and 88.1%, respectively; however, the 5-year SFRS for the patients with multisegment involvement was 44.4% and 88.1% for SC and TC, respectively. For the 5-year CFRS, the patterns of differences were similar to those of the 5-year SFRS between the 2 groups. Based on these findings and our present multivariate analysis, we suggest that SC in patients with multisegmental Crohn colitis could represent an independent risk factor for both surgical and clinical recurrence. Although SC is considered to be a valuable approach for treating single and short segment Crohn colitis,23 multiple SC to treat cases of multisegmental Crohn colitis might not be an optimal choice because of the strong effect on surgical recurrence.
Our present findings also suggested that the surgical recurrence rate of TC with ileorectal anastomosis (IRA) was 10.9% (Figure 1), which contrasted with the increased recurrence rates, that have been previously reported,12,24,25 after IRA. An earlier study reported a rate of recurrence of only 8% after IRA,26 and a meta-analysis by Polle et al11 showed there was no significant difference in the rate of recurrence between patients treated by SC versus TC with IRA. Those previous findings, along with the present results, suggest that TC with IRA could represent the surgical treatment of choice for multisegmental Crohn colitis that spares the rectum and anus.
Previous studies have demonstrated that perianal CD could represent a risk factor for surgical recurrence.12,27 Our present study has also revealed that a history of perianal disease after a first CD-related surgery could be an independent risk factor for surgical recurrence. It was previously suggested that the high risk of recurrence in patients with perianal disease might reflect a subcategory of CD that was associated with a more severe course of disease.12 Other studies that did not use biologics or autologous stem cell transplantation reported that 43% to 46% of patients potentially needed to undergo proctectomy for severe proctitis or perianal disease.28,29 The choice of a “best” operation for colonic CD cannot be solely based on the rate of recurrence, but in high-risk patients with multisegmental Crohn colitis and perianal CD, a permanent stoma might avoid the need for additional surgeries.
In contrast to a previous report,8 we did not find that TC was associated with increased complications compared with SC in our current analyses. Furthermore, patients in TC group exhibited a comparable or better nutritional state, as assessed by the recovery of weight, and levels of hemoglobin and albumin. For the nutritional state, the postoperative levels of hemoglobin significantly recovered in TC group, which might be associated with a lower rate of clinical recurrence in the TC group, compared with the SC group. Anemia is the most common systemic complication and extraintestinal manifestation of CD.30 Similar to a recent study that evaluated the effects of anti-TNF agents on levels of hemoglobin,31 we also found in our present analyses that recovery of hemoglobin levels was a risk factor for SRFS among patients with multisegmental Crohn colitis.
Whether the introduction of immunosuppressive and biological drugs can have a direct effect on the risk for surgery among patients with CD remains the subject of debate.32,33 Our present study could not demonstrate the recurrence-free survival effect of immunosuppressive drug because almost patients (83% and 86%) used the immunosuppressive drug after surgery. Into the subgroup analysis of the patients with multisegment involvement, the administration of anti-TNF agents seemed to mitigate the difference of SRFS between the SC and TC groups (CRFS, P = 0.02 and SRFS, P = 0.043; Supplement Figure 1, http://links.lww.com/MD/A1000). However, anti-TNF treatment was not a risk factor of surgical and clinical recurrence-free survival, although further studies will be needed to better characterize this potential association.
Our present study had several notable limitations. As in most single-institution retrospective observational cohort studies, potential biases for both patient referral and selection existed. Additionally, our study design lacked random experimental allocation to the SC or TC group and 2 groups were not comparable for all of the risk factors. Although the formation of permanent stoma is an important consideration for young, socially, and physically active patients, we could not collect data on the quality of life or psychological acceptance of permanent stoma because of the retrospective design of our study.
In conclusions, we found that patients who undergo TC to treat Crohn colitis exhibit a significantly reduced CRFS. We identified SC as an independent risk factor for both SRFS and CRFS. Our data also support the conclusion that total colectomy might be helpful for patients with multisegments involvement, resulting in improved SRFS and CRFS. Recovery of hemoglobin levels after surgery might represent an indicator of surgical recurrence among patients with multisegmental Crohn colitis.
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