Advanced T stage and anatomical feature of ileostomy might be risk factors of outlet obstruction following ileostomy.
Among the 83 patients with rectal cancer who underwent anterior resection, an ileostomy was created in 34 patients. Of these 34 patients, 7 (21%) experienced outlet obstruction (Table 1).
Table 1
Clinicopathological characteristics and outlet obstruction
Variable | | n | Outlet obstruction | p-value |
Negative | Positive |
(n = 27) | (n = 7) |
Physical parameter | | | | | | |
Sex | Male | 23 | 16 | 7 | 0.04* |
| Female | 11 | 11 | 0 | |
Age (y) | < 70# | 21 | 15 | 6 | 0.14 |
| ≥ 70 | 13 | 12 | 1 | |
Body Mass Index | < 25.7§ | 29 | 22 | 7 | 0.21 |
| ≥ 25.7 | 5 | 5 | 0 | |
Tumor | | | | | |
Location | Ra | 8 | 5 | 3 | 0.18 |
| Rb | 26 | 22 | 4 | |
Pathological T category | pT1/2 | 16 | 15 | 1 | 0.05* |
| pT3/4 | 18 | 12 | 6 | |
Lymph node metastasis | Absent | 27 | 22 | 5 | 0.56 |
| Present | 7 | 5 | 2 | |
Treatment | | | | | |
Neoadjuvant chemo | Absent | 21 | 15 | 6 | 0.14 |
| Present | 13 | 12 | 1 | |
Laparoscopic or open | Open | 2 | 2 | 0 | 0.46 |
| Laparoscopic | 32 | 25 | 7 | |
Operation time (min) | < 388§ | 30 | 24 | 6 | 0.82 |
| ≥ 388 | 4 | 3 | 1 | |
Anastomotic complication | Absent | 30 | 25 | 5 | 0.12 |
| Present | 4 | 2 | 2 | |
Blood exam | | | | | |
WBC (preop, /µl) | < 5050§ | 13 | 12 | 1 | 0.13 |
| ≥ 5050 | 20 | 14 | 6 | |
WBC (postop, /µl) | < 11600§ | 29 | 25 | 4 | 0.005* |
| ≥ 11600 | 4 | 1 | 3 | |
Neutrophil (preop, %) | < 72.5§ | 30 | 25 | 5 | 0.04* |
| ≥ 72.5 | 3 | 1 | 2 | |
Neutrophil (postop, %) | < 82.6§ | 25 | 21 | 4 | 0.13 |
| ≥ 82.6 | 7 | 4 | 3 | |
CRP (preop, mg/dl) | < 0.79§ | 31 | 24 | 7 | 0.45 |
| ≥ 0.79 | 2 | 2 | 0 | |
CRP (postop, mg/dl) | < 13.5§ | 22 | 19 | 3 | 0.13 |
| ≥ 13.5 | 11 | 7 | 4 | |
Ileostomy | | | | | |
Horizontal diameter (mm) | < 10.8§ | 5 | 1 | 4 | 0.0004* |
| ≥ 10.8 | 29 | 26 | 3 | |
Craniocaudal diameter (mm) | < 35§ | 31 | 25 | 6 | 0.57 |
| ≥ 35 | 3 | 2 | 1 | |
R-A muscle (postop, mm) | < 14.5§ | 26 | 25 | 1 | < 0.0001* |
| ≥ 14.5 | 8 | 2 | 6 | |
#The median age at surgery is 70 years in this cohort. §Cut off value was calculated using Yoden index. *p ≤ 0.05 |
Outlet obstruction was associated with male (p = 0.04), advanced T stage (p = 0.05), postoperative high white blood cell count (p = 0.005), preoperative high neutrophil rate (p = 0.04), long horizontal diameter of ileostomy (p = 0.0004), and thick R-A muscle (p < 0.0001).
Univariate logistic regression analysis showed that male (p = 0.01), advanced T stage (p = 0.04), postoperative high white blood cell count (p = 0.01), preoperative high neutrophil rate (p = 0.07), long horizontal diameter of ileostomy (p = 0.001), and thick R-A muscle (p < 0.0001) were risk factor of outlet obstruction. Finally, multivariate logistic regression analysis demonstrated that advanced T stage (p = 0.10), long horizontal diameter of ileostomy (p = 0.01), and thick R-A muscle (p = 0.0005) were independent risk factor of outlet obstruction (Table 2). These results suggest that advanced T stage and anatomical feature of ileostomy might be risk factors of outlet obstruction following an ileostomy.
Table 2
Univariate and multivariate analyses for the predictors of outlet obstruction
Variable | Univariate | | Multivariate |
OR | p-value | | OR | p-value |
Physical parameter | | | | | |
Sex (Male) | 1.61e + 8 | 0.01* | | 4.10 | 1.00 |
Age (< 70 y#) | 4.80 | 0.12 | | | |
Body Mass Index (< 25.7§) | 4.0.3e + 7 | 0.11 | | | |
Tumor | | | | | |
Location (Ra) | 3.30 | 0.20 | | | |
Pathological T category (pT3/4) | 7.50 | 0.04* | | 1.69e + 14 | 0.10 |
Lymph node metastasis (Present) | 1.76 | 0.57 | | | |
Treatment | | | | | |
Neoadjuvant chemo (Absent) | 4.80 | 0.12 | | | |
Laparoscopic or open (Laparoscopic) | 3.05e + 6 | 0.33 | | | |
Operation time (≥ 388 min§) | 1.33 | 0.82 | | | |
Anastomotic complication (Present) | 5.00 | 0.16 | | | |
Blood exam | | | | | |
WBC (preop, ≥ 5050 /µl§) | 5.14 | 0.11 | | | |
WBC (postop, ≥ 11600 /µl§) | 18.75 | 0.01* | | 2.31 | 1.00 |
Neutrophil (preop, ≥ 72.5%§) | 10.00 | 0.07 | | | |
Neutrophil (postop, ≥ 82.6%§) | 3.94 | 0.15 | | | |
CRP (preop, ≥ 0.79 mg/dl§) | 3.15e-7 | 0.32 | | | |
CRP (postop, ≥ 13.5 mg/dl§) | 3.62 | 0.14 | | | |
Ileostomy | | | | | |
Horizontal diameter (< 10.8 mm§) | 34.7 | 0.001* | | 5.84e + 14 | 0.01* |
Craniocaudal diameter (≥ 35mm§) | 2.08 | 0.59 | | | |
R-A muscle (postop, ≥ 14.5 mm§) | 75.0 | < 0.0001* | | 1.59e + 15 | 0.0005* |
#The median age at surgery is 70 years in this cohort. §Cut off value was calculated using Yoden index. *p ≤ 0.05 |
Outlet obstruction following ileostomy was a risk factor of HOS
Not only outlet obstruction, but also HOS is an important complication of ileostomy. We next examined the relationship between outlet obstruction and HOS. HOS was defined as more than 1500 mL of ileostomy discharge. Ileostomy discharge was determined at postoperative days 3, 4, and 5 in the outlet obstruction positive and negative groups.
The amount of ileostomy discharge was higher in the outlet obstruction positive group than in the outlet obstruction negative group (day 3: p = 0.06, day 4: p = 0.03, day 5: p = 0.007; Fig. 2A). When HOS was defined as more than 1500 mL of ileostomy discharge, the probability of HOS was higher in the outlet obstruction positive group than in the outlet obstruction negative group (day 3: p = 0.05, day 4: p = 0.02, day 5: p = 0.06; Fig. 2B). These results suggest that outlet obstruction might be a risk factor of HOS.
Advanced T stage and anatomical feature of ileostomy might be risk factors of HOS
Considering that advanced T stage and anatomical feature of ileostomy were risk factors of outlet obstruction, we next assessed whether these factors were also associated with HOS, which showed significant correlation with outlet obstruction.
HOS was related to high BMI (p = 0.07), advanced T stage (p = 0.02), preoperative high white blood cell count (p = 0.06), postoperative high white blood cell count (p = 0.07), postoperative high neutrophil rate (p = 0.08), and thick R-A muscle (p = 0.02; Table 3).
Table 3
Clinicopathological characteristics and high-output stoma
Variable | | n | High-output stoma (day4) | p-value |
Negative | Positive |
(n = 21) | (n = 11) |
Physical parameter | | | | | |
Sex | Male | 21 | 12 | 9 | 0.16 |
| Female | 11 | 9 | 2 | |
Age (y) | < 70# | 20 | 12 | 8 | 0.39 |
| ≥ 70 | 12 | 9 | 3 | |
Body Mass Index | < 25.7§ | 28 | 20 | 8 | 0.07 |
| ≥ 25.7 | 4 | 1 | 3 | |
Tumor | | | | | |
Location | Ra | 8 | 5 | 3 | 0.83 |
| Rb | 24 | 16 | 8 | |
Pathological T category | pT1/2 | 15 | 13 | 2 | 0.02* |
| pT3/4 | 17 | 8 | 9 | |
Lymph node metastasis | Absent | 25 | 17 | 8 | 0.59 |
| Present | 7 | 4 | 3 | |
Treatment | | | | | |
Neoadjuvant chemo | Absent | 20 | 13 | 7 | 0.92 |
| Present | 12 | 8 | 4 | |
Laparoscopic or open | Open | 2 | 2 | 0 | 0.29 |
| Laparoscopic | 30 | 19 | 11 | |
Operation time (min) | < 388§ | 29 | 19 | 10 | 0.97 |
| ≥ 388 | 3 | 2 | 1 | |
Anastomotic complication | Absent | 29 | 20 | 9 | 0.22 |
| Present | 3 | 1 | 2 | |
Blood exam | | | | | |
WBC (preop, /µl) | < 5050§ | 13 | 11 | 2 | 0.06 |
| ≥ 5050 | 19 | 10 | 9 | |
WBC (postop, /µl) | < 11600§ | 28 | 20 | 8 | 0.07 |
| ≥ 11600 | 4 | 1 | 3 | |
Neutrophil (preop, %) | < 72.5§ | 29 | 20 | 9 | 0.22 |
| ≥ 72.5 | 3 | 1 | 2 | |
Neutrophil (postop, %) | < 82.6§ | 25 | 18 | 7 | 0.08 |
| ≥ 82.6 | 6 | 2 | 4 | |
CRP (preop, mg/dl) | < 0.79§ | 30 | 20 | 10 | 0.63 |
| ≥ 0.79 | 2 | 1 | 1 | |
CRP (postop, mg/dl) | < 13.5§ | 22 | 16 | 6 | 0.21 |
| ≥ 13.5 | 10 | 5 | 5 | |
Ileostomy | | | | | |
Horizontal diameter (mm) | < 10.8§ | 5 | 3 | 2 | 0.77 |
| ≥ 10.8 | 27 | 18 | 9 | |
Craniocaudal diameter (mm) | < 35§ | 29 | 18 | 11 | 0.19 |
| ≥ 35 | 3 | 3 | 0 | |
R-A muscle (postop, mm) | < 14.5§ | 25 | 19 | 6 | 0.02* |
| ≥ 14.5 | 7 | 2 | 5 | |
#The median age at surgery is 70 years in this cohort. §Cut off value was calculated using Yoden index. *p ≤ 0.05 |
Univariate logistic regression analysis demonstrated that high BMI (p = 0.07), advanced T stage (p = 0.02), preoperative high white blood cell count (p = 0.05), postoperative high white blood cell count (p = 0.07), postoperative high neutrophil rate (p = 0.08), long craniocaudal diameter of ileostomy (p = 0.10), and thick R-A muscle (p = 0.02) were risk factor of HOS. Finally, multivariate logistic regression analysis demonstrated that advanced T stage (p = 0.03), and thick R-A muscle (p = 0.04) were independent risk factor of HOS (Table 4). These results suggest that advanced T stage and anatomical feature of ileostomy might be also risk factors of HOS, similar to outlet obstruction.
Table 4
Univariate and multivariate analysis for the predictors of high-output stoma
Variable | Univariate | | Multivariate |
OR | p-value | | OR | p-value |
Physical parameter | | | | | |
Sex (Male) | 3.38 | 0.15 | | | |
Age (< 70 y#) | 2.00 | 0.38 | | | |
Body Mass Index (≥ 25.7§) | 7.5 | 0.07 | | | |
Tumor | | | | | |
Location (Ra) | 1.2 | 0.83 | | | |
Pathological T category (pT3/4) | 7.31 | 0.02* | | 6.88 | 0.03* |
Lymph node metastasis (Present) | 1.59 | 0.60 | | | |
Treatment | | | | | |
Neoadjuvant chemo (Absent) | 1.08 | 0.92 | | | |
Laparoscopic or open (Laparoscopic) | 5.98e + 7 | 0.33 | | | |
Operation time (< 388 min§) | 1.05 | 0.97 | | | |
Anastomotic complication (Present) | 4.44 | 0.23 | | | |
Blood exam | | | | | |
WBC (preop, ≥ 5050 /µl§) | 4.95 | 0.05 | | | |
WBC (postop, ≥ 11600 /µl§) | 7.50 | 0.07 | | | |
Neutrophil (preop, ≥ 72.5%§) | 4.44 | 0.23 | | | |
Neutrophil (postop, ≥ 82.6%§) | 5.14 | 0.08 | | | |
CRP (preop, ≥ 0.79 mg/dl§) | 2.00 | 0.64 | | | |
CRP (postop, ≥ 13.5 mg/dl§) | 2.67 | 0.21 | | | |
Ileostomy | | | | | |
Horizontal diameter (< 10.8 mm§) | 1.33 | 0.78 | | | |
Craniocaudal diameter (< 35mm§) | 7.53e + 7 | 0.10 | | | |
R-A muscle (postop, ≥ 14.5 mm§) | 7.92 | 0.02* | | 7.35 | 0.04* |
#The median age at surgery is 70 years in this cohort. §Cut off value was calculated using Yoden index. *p ≤ 0.05 |
Ileostomy location was important to prevent outlet obstruction and HOS following ileostomy
Our investigation of the clinical data suggested that advanced T stage and thick R-A muscle were the common risk factors of outlet obstruction and HOS. Although it is difficult to prove a relationship between these two phenomena, we would like to propose the “malignant cycle theory” that considers these phenomena (Fig. 3A).
The trigger of this cycle is incomplete ileostomy obstruction, mainly because of a thick R-A muscle causing high resistance. Owing to the incomplete obstruction, the amount of upper intestinal secretion increases via mucosal edema. Even when the amount of ileostomy discharge appears to be enough, the condition of the intestinal fluid reservoir worsens because of fluid supply overload, and this is followed by progressive relative ileostomy obstruction. Additionally, advanced T stage induces preoperative intestinal obstruction, edema, and inflammation, leading to high output stoma and relative outlet obstruction. Elevated white blood cell count (p = 0.05) in patients with advanced CRC supports this hypothesis (Table 5). After the initiation of this malignant cycle, it will be difficult to stop outlet obstruction and HOS, and ileostomy drainage by tubing will be needed.
Table 5
Clinicopathological characteristics and pathological T stage
Variable | | n | Pathological T category | p-value |
pT1/2 | pT3/4 |
(n = 16) | (n = 18) |
Treatment | | | | | |
Laparoscopic or open | Open | 2 | 0 | 2 | 0.17 |
| Laparoscopic | 32 | 16 | 16 | |
Operation time (min) | < 388§ | 30 | 14 | 16 | 0.90 |
| ≥ 388 | 4 | 2 | 2 | |
Anastomotic complication | Absent | 30 | 14 | 16 | 0.90 |
| Present | 4 | 2 | 2 | |
Blood exam | | | | | |
WBC (preop, /µl) | < 5050§ | 13 | 9 | 4 | 0.05* |
| ≥ 5050 | 20 | 7 | 13 | |
WBC (postop, /µl) | < 11600§ | 29 | 15 | 14 | 0.32 |
| ≥ 11600 | 4 | 1 | 3 | |
Neutrophil (preop, %) | < 72.5§ | 30 | 16 | 14 | 0.08 |
| ≥ 72.5 | 3 | 0 | 3 | |
Neutrophil (postop, %) | < 82.6§ | 25 | 13 | 12 | 0.27 |
| ≥ 82.6 | 7 | 2 | 5 | |
CRP (preop, mg/dl) | < 0.79§ | 31 | 16 | 15 | 0.16 |
| ≥ 0.79 | 2 | 0 | 2 | |
CRP (postop, mg/dl) | < 13.5§ | 22 | 12 | 10 | 0.32 |
| ≥ 13.5 | 11 | 4 | 7 | |
Ileostomy | | | | | |
Horizontal diameter (mm) | < 10.8§ | 5 | 2 | 3 | 0.73 |
| ≥ 10.8 | 29 | 14 | 15 | |
Craniocaudal diameter (mm) | < 35§ | 31 | 14 | 17 | 0.48 |
| ≥ 35 | 3 | 2 | 1 | |
R-A muscle (preop, mm) | < 11.2§ | 23 | 14 | 9 | 0.007* |
| ≥ 11.2 | 10 | 1 | 9 | |
R-A muscle (postop, mm) | < 14.5§ | 26 | 14 | 12 | 0.15 |
| ≥ 14.5 | 8 | 2 | 6 | |
§Cut off value was calculated using Yoden index. *p ≤ 0.05 |
As the initiator of outlet obstruction is a thick R-A muscle, we believe that the most important point is ileostomy location. On cross-section assessment, the R-A muscle has a flat, oval shape, and it is thinner at the lateral side. Thus, even if a patient has a thick R-A muscle, when an ileostomy is created at the lateral side, the R-A muscle thickness close to the ileostomy will be lower than that at the middle, resulting in the prevention of outlet obstruction and HOS following the ileostomy (Fig. 3B). Considering that the pipe flow resistance is proportional to its length and inversely proportional to its diameter (Darcy–Weisbach Equation), our hypothesis will be also supported by the theory of fluid mechanics [7].