Significance of information obtained during transanal drainage tube placement after anterior resection of colorectal cancer.

INTRODUCTION: It has recently been reported that the placement of a transanal drainage tube after rectal cancer surgery reduces the rate of anastomotic leakage. However, transanal drainage tube cannot completely prevent anastomotic leakage and the management of transanal drainage tube needs to devise. We investigated the information obtained during transanal drainage tube placement and evaluated the relationship between these factors and anastomotic leakage. PATIENTS AND METHODS: Fifty-one patients who underwent anterior resection of rectal cancer was retrospectively reviewed. transanal drainage tube was placed for more than 5 days after surgery. The daily fecal volume from transanal drainage tube was measured on postoperative day 1-5, and the defecation during transanal drainage tube placement was investigated.
RESULTS: Anastomotic leakage during transanal drainage tube placement occurred in 4 patients. The anastomotic leakage rate during transanal drainage tube placement in patients whose maximum daily fecal volume or total fecal volume from the transanal drainage tube during postoperative days 1-5 was large was significantly higher than that in patients whose fecal volume was small. The anastomotic leakage rate of the patients with intentional defecation during transanal drainage tube placement was significantly higher than that of the patients without intentional defecation during transanal drainage tube placement. The maximum daily fecal volume and the total fecal volume from the transanal drainage tube during postoperative days 1-5 in patients who experienced intentional defecation during transanal drainage tube placement was significantly higher than that of patients without intentional defecation during transanal drainage tube placement.
CONCLUSION: A large fecal volume from transanal drainage tube after anterior rectal resection or intentional defecation in patients with transanal drainage tube placement were suggested to be risk factors for anastomotic leakage.

Introduction

Anastomotic leakage after the resection of colorectal cancer is a serious complication that is associated with short-term outcomes, such as reoperation, extension of hospital stay, and increased perioperative mortality [1-5], as well as long-term oncological effects, such as a poor prognosis due to local recurrence [6-8]. The anastomotic leakage rate after resection of rectal cancer is higher in comparison to other colon cancers [9]. Thus, in order to prevent anastomotic leakage after low-anterior resection (LAR) of the rectum, various methods have been adapted, such as adequate mobilization of the colon [10], the use of intracorporeal reinforcing sutures [11] and evaluation of the blood flow by fluorescence imaging with indocyanine green (ICG) [12]. In addition, in cases in which there is considered to be a high risk of anastomotic leakage, such as cases with anastomosis at a low rectal position, diverting stomas can be constructed to reduce the burden of anastomosis [13]. Recently, it has been reported that the placement of a transanal drainage tube (TDT), which is technically easy and which can economically decompress the anastomotic site [14], is effective for preventing anastomotic leakage after rectal cancer surgery [15-17]. However, even if a TDT is used, defecation may occur that does not pass through the TDT, and anastomotic leakage may occur. Furthermore, the timing of the removal of the TDT was sometimes delayed based on the judgment of each surgeon. Thus, there may be room for improving the method of managing TDT in the perioperative period. The present study therefore explored the mechanism underlying the occurrence of anastomotic leakage despite using a TDT by evaluating the association between the perioperative clinical information obtained during TDT placement and anastomotic leakage and suggested a strategy for preventing anastomotic leakage. Thus, we retrospectively evaluated the association between clinical information during TDT placement and anastomotic leakage.

Patients and methods

Fifty-one consecutive patients underwent surgery for the treatment of colorectal cancer with the double staple technique (DST) and who underwent TDT placement for 5 days or more after surgery, at Osaka City University Hospital between January 2016 and March 2019. None of the 51 patients underwent construction of a diverting stoma. Patients treated with preoperative chemotherapy or chemoradiotherapy, and those who underwent decompression treatment for intestinal obstruction were excluded from the present study. The characteristics and clinical information of the 51 patients were retrospectively based on their electronic medical records. The associations between anastomotic leakage and preoperative risk factors for anastomotic leakage, such as male sex, advanced age, obesity, high primary T/N stage, large-diameter tumor and anastomosis at a low position [18-21] were evaluated. The World Health Organization has reported that the body mass index (BMI; weight / length2) ≥25.0 kg/m2 indicates an overweight status [22]. We therefore set 25.0 kg/m2 as the cut-off value of the BMI. The primary pathological T/N stage was defined by the Union for International Cancer Control (UICC) 8th edition [23]. The patients were classified into T1-3 and T4 groups or N0 and N1-3 groups. They were also divided into high-anterior resection (HAR) and LAR groups. The tumor diameter was determined based on the maximum length of the tumor. Tumor diameter was defined as 0 after endoscopic treatment. The cut-off value for the tumor diameter was calculated based on the receiver operating characteristic (ROC) curve.

The standard mechanical bowel preparation at our hospital was fasting after lunch and the internal use of polyethylene glycol solution at 14:00 on the day before surgery. However, two patients had diarrhea before the mechanical bowel preparation. No patients received antibiotic prophylaxis. For all the patients, a 10-mm Pleats drain (Akita Sumitomo Bakelite, Japan) was inserted from the anus and positioned with the tip approximately 5 cm above the anastomotic site at the last step of the colorectal cancer operation under general anesthesia. The removal of the TDT was scheduled for postoperative day (POD) 5; however, removal was sometimes delayed depending on the judgment of each surgeon.

The daily fecal volume from TDT and the total fecal volume for the 5 days of TDT placement (PODs 1–5 after the resection for CRC) were measured.

The cut-off values of the fecal volume were calculated based on an ROC curve analysis in order to determine the relationship between anastomotic leakage and the fecal volume from the TDT. The patients were divided to two groups: the high-volume group and the low-volume group.

The fecal matter that did not pass through the TDT during POD 1–5 was investigated from electronic medical records. In this study, the defecation that patients consciously performed during TDT placement was defined as intentional defecation, while the discharge that flowed outside the TDT unconsciously was defined as fecal incontinence. We evaluated the associations between anastomotic leakage and intentional defecation and between anastomotic leakage and fecal incontinence.

In addition, a subgroup analysis of patients in whom no anastomotic leakage occurred during TDT placement was performed. The association between the fecal volume from the TDT at POD 5, when TDT removal was scheduled, and the anastomotic leakage after removal of TDT was evaluated.

The details of anastomotic leakage were collected from the medical records of each surgeon. Anastomotic leakage was defined by major leakage (e.g., fecal discharge from the abdominal drain tube or the discharging of contrast agent into the abdominal cavity during fluoroscopic examination) and by minor leakage (e.g., free air around the anastomotic site on CT after the patient presented fever or abdominal pain).

All of the statistical analyses were performed using JMP 14.2.0 (SAS Institute, Japan, Tokyo). The chi-squared test, the Fisher’s exact test and Mann-Whitney U-test were used to analyze the significance of associations between 2 groups. P values of <0.05 were considered to indicate statistical significance. Baseline variables with p values of <0.10 on the univariate analysis were included as covariates in the multivariate logistic regression analysis. P values of <0.05 were considered to indicate statistical significance.

This retrospective study was approved by the Ethics Committee of Osaka City University (approval number: 4182) and conducted in accordance with the Declaration of Helsinki. All patients provided their written informed consent.

Results

Patient characteristics

The patient characteristics are listed in Table 1. Of the 51 patients who were analyzed, 32 were male and 19 were female. The median age was 70 years (range: 41–87). The median BMI was 23.8 kg/m2 (range: 15.4–33.5). The pathological T stage of 47 patients was T1-3, and that of 4 patients was T4. The pathological N stage of 43 patients was N0, and that of 8 patients was N1-3. The median tumor diameter was 30.0 mm (range: 0–100.0 mm). LAR was performed for 23 patients and HAR was performed for 28 patients. Laparoscopic operations were performed for 48 patients and open surgery was performed for 3 patients.

Table 1

Patient characteristics.

Clinical factor	n = 51
Gender, n(%)
Male	32 (62.7%)
Female	19 (37.3%)
Age (years)
Median (range)	70 (41–87)
BMI (kg/m2)
Median (range)	23.8 (15.4–33.5)
Pathologic T stage
T1	18 (35.3%)
T2	6 (11.8%)
T3	23 (45.1%)
T4	4 (7.8%)
Pathologic N stage
N0	43 (84.3%)
N1	5 (9.8%)
N2	2 (3.9%)
N3	1 (2.0%)
Diameter of tumor (mm)
Median (range)	30.0 (0–100.0)
Operative method, n(%)
High-anterior resection	28 (54.9%)
Low-anterior resection	23 (45.1%)
Surgical approach, n(%)
Laparoscopic surgery	48 (94.1%)
Open surgery	3 (5.9%)

BMI: Body Mass Index

Preoperative factors associated with anastomotic leakage

The median tumor diameter of the patients without anastomotic leakage was 28.0mm (range 0 to 100.0; interquartile range 15.0 to 43.0). The median tumor diameter of the patients who experienced anastomotic leakage was 55.0mm (range 35.0 to 80.0; interquartile range 40.0 to 73.8). The tumor diameter of the patients who experienced anastomotic leakage was significantly greater than that of the patients without anastomotic leakage (p = 0.021) (S1 Fig).

We used the tumor diameter, which was a continuous variable, as the test variable and the occurrence of anastomotic leakage as the state variable. When we investigated the cut-off value for the tumor diameter using the ROC curve, we found that the appropriate cut-off value for the tumor diameter was 35.0 mm (sensitivity of 87.5%; specificity of 67.4%) (S2 Fig). We therefore set 35.0 mm as the cut-off value and classified patients into high and low groups based on this value.

The anastomotic leakage rate was significantly higher in the groups with LAR and ≥35.0 mm tumor diameter than in the other groups (p = 0.016, p = 0.006, respectively) (Table 2).

Table 2

Preoperative factors associated with anastomotic leakage.

	Anastomotic leakage
Preoperative factor	Negative (n = 43)	Positive (n = 8)	p-value
Gender, n(%)
Male	27 (62.8%)	5 (62.5%)	>0.999
Female	16 (37.2%)	3 (37.5%)
Age(years)	70	62.5	0.161
Median(range)	(41–87)	(51–80)
BMI, n(%)
≥25.0kg/m2	17 (39.5%)	2 (25.0%)	0.694
<25.0kg/m2	26 (60.5%)	6 (75.0%)
Pathological T stage
≤T3	40 (93.0%)	7 (87.5%)	0.506
T4	3 (7.0%)	1 (12.5%)
Pathological N stage
N0	36 (83.5%)	7 (87.5%)	>0.999
≥N1	7 (16.5%)	1 (12.5%)
Diameter of tumor, n(%)
≥35.0 mm	14 (32.6%)	7 (87.5%)	0.006
<35.0 mm	29 (67.4%)	1 (12.5%)
Operative method, n(%)
High-anterior resection	27 (62.8%)	1 (12.5%)	0.016
Low-anterior resection	16 (37.2%)	7 (87.5%)

BMI: Body Mass Index

Occurrence and timing of anastomotic leakage

Anastomotic leakage occurred in 8 patients (15.7%). Four of these 8 cases occurred during TDT placement, and 4 of the 8 cases occurred after the removal of the TDT. Major leakage occurred in 2 patients (3.9%), and minor leakage occurred in 6 patients (11.8%). Re-operation for anastomotic leakage was performed in the 2 major leakage patients (3.9%). Of the four cases of anastomotic leakage during TDT placement, major leakage occurred in two patients, and minor leakage occurred in the other two. All four instances of anastomotic leakages after the removal of the TDT were minor.

Association between the fecal volume from the TDT during POD 1–5 and the anastomotic leakage during TDT placement

The median maximum fecal volume from the TDT during POD 1–5 in patients who experienced anastomotic leakage during TDT placement was 275.0ml (range 100.0 to 400.0; interquartile range 125.0 to 388.0). The median maximum fecal volume from the TDT during POD 1–5 of the patients without anastomotic leakage during TDT placement was 40.0ml (range 0 to 680.0; interquartile range 8.0 to 100.0). The maximum fecal volume from the TDT during POD 1–5 in patients who experienced anastomotic leakage during TDT placement was significantly greater than that of the patients without anastomotic leakage during TDT placement (p = 0.010) (Fig 1A). The median total fecal volume from the TDT during POD 1–5 in patients who experienced anastomotic leakage during TDT placement was 522.0ml (range 260.0 to 720.0; interquartile range 292.5 to 703.8). The median total fecal volume from the TDT during POD 1–5 of the patients without anastomotic leakage during TDT placement was 80.0ml (range 0 to 1970.0; interquartile range 9.0 to 220.0). The total fecal volume from the TDT during POD 1–5 in patients who experienced anastomotic leakage during TDT placement was significantly higher than that of the patients without anastomotic leakage during TDT placement (p = 0.010) (Fig 1B).

Fig 1

Association between anastomotic leakage during transanal drainage tube placement and the fecal volume from the transanal drainage tube.

(a) The anastomotic leakage during transanal drainage tube (TDT) placement-positive group had a significantly greater maximum daily fecal volume during POD 1–5 than the anastomotic leakage during TDT placement-negative group (median total fecal volume: 275.0 ml vs. 40.0 ml, respectively. p = 0.010). (b) The anastomotic leakage during TDT placement-positive group had a significantly greater total fecal volume during POD 1–5 than the anastomotic leakage during TDT placement-negative group (median total fecal volume: 522.0 ml vs. 80.0 ml, respectively. p = 0.010).

We used the maximum daily fecal volume from the TDT during PODs 1–5, which was a continuous variable, as the test variable and the occurrence of anastomotic leakage during the TDT placement as the state variable. When we investigated the cut-off value for the maximum daily fecal volume from the TDT during PODs 1–5 using the ROC curve, we found that the appropriate cut-off value for the maximum daily fecal volume was 100.0 ml (sensitivity of 100.0%; specificity of 74.5%) (S3A Fig). Using the ROC curve in the same manner, we set the cut-off value for the total fecal volume from the TDT during PODs 1–5 at 260.0 ml (sensitivity of 100.0%; specificity of 83.0%) (S3B Fig). We therefore set each of these values of fecal volume as the relevant cut-off values and classified patients into the high and low groups.

The anastomotic leakage rate during TDT placement in patients in whom the maximum daily fecal volume from the TDT during POD 1–5 was ≥100.0 ml was significantly higher than that of the patients in whom the maximum daily fecal volume from the TDT during POD 1–5 was <100.0 ml (p = 0.007). The anastomotic leakage rate during TDT placement in patients in whom the total fecal volume from the TDT during POD 1–5 was ≥260.0 ml was significantly higher than that of the patients in whom the total fecal volume from the TDT during POD 1–5 was <260.0 ml (p = 0.002) (Table 3).

Table 3

Association between the fecal volume from the transanal drainage tube during postoperative day 1 to 5 and the anastomotic leakage during placement of transanal drainage tube.

	Anastomotic leakage during TDT placement		p-value
	Negative (n = 47)	Positive (n = 4)
Maximum daily fecal volume from TDT during POD1 to 5, n(%)
≥100.0 ml	12 (25.5%)	4 (100.0%)	0.007
<100.0 ml	35 (74.5%)	0 (0%)
Total fecal volume from TDT during POD1 to 5, n(%)
≥260.0 ml	8 (11.6%)	4 (100.0%)	0.002
<260.0 ml	39 (88.4%)	0 (0%)

TDT: Transanal drainage tube, POD: postoperative day

Association between fecal discharge not through TDT and the anastomotic leakage during TDT placement

The anastomotic leakage rate of the patients who experienced fecal incontinence during TDT placement was not significantly different from that in patients without fecal incontinence during TDT placement. However, the anastomotic leakage rate of patients who experienced intentional defecation during TDT placement was significantly higher than that of patients without intentional defecation during TDT placement (p = 0.028) (Table 4).

Table 4

Association between the anastomotic leakage during placement of transanal drainage tube and fecal discharge not through transanal drainage tube during transanal drainage tube placement.

	Anastomotic leakage during TDT placement		p-value
	Negative (n = 47)	Positive (n = 4)
Fecal incontinence, n(%)
	42 (89.4%)	4 (100.0%)	>0.999
Yes	5 (10.6%)	0 (0%)
Intentional defecation, n(%)
No	39 (83.0%)	1 (25.0%)	0.028
Yes	8 (17.0%)	3 (75.0%)

TDT: transanal drainage tube

Association between intentional defecation during TDT placement and the fecal volume from TDT

The median maximum fecal volume from the TDT during POD 1–5 in patients who experienced intentional defecation during TDT placement was 100.0ml (range 10.0 to 400.0; interquartile range 30.0 to 350.0). The median maximum fecal volume from the TDT during POD 1–5 in patients without intentional defecation during TDT placement was 35.0ml (range 0 to 680.0; interquartile range 2.3 to 95.0). The maximum fecal volume from the TDT during POD 1–5 in patients who experienced intentional defecation during TDT placement was significantly higher than that of patients without intentional defecation during TDT placement (p = 0.026) (Fig 2A). The median total fecal volume from the TDT during POD 1–5 in patients who experienced intentional defecation during TDT placement was 242.0ml (range 42.0 to 720.0; interquartile range 120.0 to 655.0). The median total fecal volume from the TDT during POD 1–5 in patients without intentional defecation during TDT placement was 68.0ml (range 0 to 1970.0; interquartile range 6.0 to 215.0). The total fecal volume from the TDT during POD 1–5 in patients who experienced intentional defecation during TDT placement was significantly higher than that of patients without intentional defecation during TDT placement (p = 0.010) (Fig 2B).

Fig 2

Association between intentional defecation and the fecal volume from the transanal drainage tube.

(a) The defecation-positive group have a significantly greater maximum daily fecal volume during postoperative days 1–5 in comparison to the defecation-negative group (Median total fecal volume: 100.0 ml vs. 35.0 ml, respectively. p = 0.026). (b) The defecation-positive group have a significantly greater total fecal volume during postoperative days 1–5 in comparison to the defecation-negative group (Median total fecal volume: 242.0 ml vs. 68.0 ml, respectively. p = 0.010).

The evaluation of risk factors of anastomotic leakage during TDT placement

The correlation between anastomotic leakage during TDT placement and risk factors was evaluated. In the univariate analysis, the anastomotic leakage rate during TDT placement in the group with a tumor diameter ≥35 mm and the group with a total fecal volume from TDT ≥260 ml during the first 5 postoperative days was significantly higher than in the group with a tumor diameter <35 mm and the group with a total fecal volume from TDT <260 ml (p = 0.006 and p = 0.0004, respectively). The multivariate analysis indicated that a large tumor diameter and total fecal volume from TDT during the first 5 postoperative days were independent risk factors for anastomotic leakage during TDT placement (p = 0.041 and p = 0.002, respectively) (Table 5).

Table 5

Univariate and multivariate analysis of risk factors of anastomotic leakage during TDT placement.

	univariate analysis			multivariate analysis
	HR	95% CI	p-value	HR	95% CI	p-value
Sex (male vs. female)	5.813	0.559–60.47	0.109
Age (<70 vs. ≥70)	2.875	0.279–29.68	0.345
BMI (<25kg/m2 vs. ≥25kg/m2)	0.537	0.052–5.566	0.587
Diameter of tumor (<35 mm vs. ≥35 mm)	8.901×107	Not evaluable	0.006	2.0×108	Not evaluable	0.041
The distance from anal marge (HAR vs. LAR)	4.05	0.392–41.87	0.206
Total fecal volume from TDT during postoperative 5 days (<260 ml vs. ≥260 ml)	1.924×108	Not evaluable	0.0004	5.599×108	Not evaluable	0.002

HR: hazard ratio, CI: confidence interval, BMI: body mass index, HAR: high anterior resection, LAR: low anterior resection, TDT: transanal drainage tube

Preoperative factors that were associated with the postoperative fecal volume from TDT

The total fecal volume from the TDT during POD 1–5 in patients in whom the tumor diameter was ≥35.0 mm tended to be higher than that of the patients in whom the tumor diameter was <35.0 mm (p = 0.051) (Table 6).

Table 6

Association between preoperative factors and the postoperative fecal volume from the transanal drainage tube.

Preoperative factor	Maximum daily fecal volume from TDT during POD1 to 5			Total fecal volume from TDT during POD1 to 5
	<100.0 ml (n = 35)	≥100.0 ml (n = 16)	p-value	<260.0 ml (n = 39)	≥260.0 ml (n = 12)	p-value
Gender, n (%)
Male	22 (62.9%)	10 (62.5%)	>0.999	24 (61.5%)	8 (66.7%)	0.872
Female	13 (37.1%)	6 (37.5%)		15 (38.5%)	4 (33.3%)
Age (years)	69 (41–87)	72 (47–81)	0.684	70 (41–87)	70 (51–77)	0.601
Median (range)
Operative method, n(%)
High-anterior resection	20 (57.1%)	8 (50.0%)	0.764	23 (41.0%)	5 (41.7%)	0.292
Low-anterior resection	15 (42.9%)	8 (50.0%)		16 (59.0%)	7 (58.3%)
Diameter of tumor, n (%)
<35.0 mm	22 (62.9%)	8 (50.0%)	0.541	26 (66.7%)	4 (33.3%)	0.051
≥35.0 mm	13 (37.1%)	8 (50.0%)		13 (33.3%)	8 (66.7%)
Surgical approach, n (%)
Laparoscopic surgery	32 (91.4%)	16 (100%)	0.543	36 (92.3%)	12 (100%)	>0.999
Open surgery	3 (8.6%)	0 (0%)		3 (7.7%)	0 (0%)

TDT: Transanal drainage tube; POD: postoperative day

The subgroup analysis of the anastomotic leakage that occurred after TDT removal, among the patients who did not develop anastomotic leakage during TDT placement

Among the 47 patients who did not develop anastomotic leakage during TDT placement, 4 patients developed anastomotic leakage after removal of the TDT.

We used the daily fecal volume from the TDT on POD 5, which was a continuous variable, as the test variable and the occurrence of anastomotic leakage after removal of the TDT as the state variable. When we investigated the cut-off value for the daily fecal volume from the TDT on POD 5 using the ROC curve, we found that the appropriate cut-off value for the daily fecal volume from the TDT on POD 5 was 80.0 ml (sensitivity of 50.0%; specificity of 86.0%) (S4 Fig). We therefore set this fecal volume as the cut-off value and classified patients into high and low groups.

The anastomotic leakage rate after removal of the TDT of patients for whom the daily fecal volume from the TDT on POD 5 was ≥80.0 ml tended to be higher in comparison to the patients for whom the daily fecal volume from the TDT on POD 5 was <80.0 ml (p = 0.067) (Table 7).

Table 7

In the subgroup of 47 patients in whom no anastomotic leakage occurred during TDT placement, the association between the fecal volume from the transanal drainage tube on postoperative day 5 and the anastomotic leakage after removal of the transanal drainage tube.

	Anastomotic leakage after removal of TDT		p-value
	Negative (n = 43)	Positive (n = 4)
Daily fecal volume from TDT of POD5, n(%)
≥80.0 ml	6 (14.0%)	2 (50.0%)	0.067
<80.0 ml	37 (86.0%)	2 (50.0%)

TDT: Transanal drainage tube; POD: Postoperative day

Discussion

For many years, various methods have been adopted to prevent anastomotic leakage after surgery for rectal cancer. At our hospital, we confirm during surgery that the anastomotic site was not strained by noting sufficient descending colon mobilization. As needed, we add splenic flexura mobilization. We also confirm that sufficient blood flow is maintained to the distal resection margin. However, despite such management, the issue of anastomotic leakage remains.

TDT placement is as an easy and economical method for decompressing anastomosis. TDT was shown to be associated with patient discomfort [24] and a risk of bowel perforation [25, 26]. However, some reports have revealed that TDT placement reduces the rate of anastomotic leakage after resection of rectal cancer [27], and TDT placement for such reasons has now become popular. In addition, TDT was expected to reduce the discharge of feces into the abdominal cavity when anastomotic leakage occurred. TDT also has an advantage in that anastomotic leakage can be efficiently treated using both a TDT and an abdominal drainage tube when conservative treatment is performed [27].

Watery stool in the early period after surgery for rectal cancer has been reported to be a risk factor for anastomotic leakage [28-31]. However, there have been few reports on this topic and the relationship between the fecal volume after surgery and anastomotic leakage has remained unclear. In recent years, the TDT placement after surgery for rectal cancer has been widely performed, which has enabled the fecal volume from TDTs to be analyzed in detail. This has revealed an association between anastomotic leakage and the fecal volume from the TDT. The present study revealed that an increased fecal volume from the TDT was significantly associated with an increased rate of anastomotic leakage. These findings were in accordance with the results of previous studies, which found that the anastomotic leakage was associated with the fecal volume from the TDT after laparoscopic LAR [20, 29]. In our multivariate analysis, a large fecal volume from the TDT was an independent risk factor for anastomotic leakage during TDT placement. Based on the present findings in addition to the previously reported preoperative risk factors of anastomotic leakage, such as the tumor diameter or distance from the anal verge to the tumor, a large fecal volume from TDT was considered an important risk factor of anastomotic leakage.

In clinical practice, the defecation of watery stool which does not pass through the TDT may sometimes occur in spite of TDT placement after surgery. We therefore evaluated the correlation between defecation occurring during TDT placement and anastomotic leakage/fecal volume from the TDT. Our study revealed that intentional defecation during TDT placement was significantly associated with an increased anastomotic leakage rate. In addition, patients with intentional defecation during TDT placement had a significantly greater fecal volume after surgery than patients without intentional defecation during TDT placement. Given these results, one of the mechanisms underlying anastomotic leakage during TDT placement was suggested to involve a large volume of watery stool that occurred after surgery causing a large fecal volume from the TDT. Furthermore, when the volume of watery stool was larger than the volume that could flow through the TDT, it caused poor drainage from the rectum, and the remaining fecal matter in the rectum increased the risk of intentional defecation. With the intestinal pressure increasing many times due to intentional defecation, the substantial physical burden occurring at the site of anastomosis would then cause anastomosis rupture.

Several preoperative factors were expected to be related to the presence of watery stool in the early period after surgery increasing the fecal volume from the TDT. In our study, a tumor diameter ≥35 mm was suggested to be a risk factor for an increased fecal volume from the TDT after surgery. This may be because a large tumor can cause stenosis of the bowel, resulting in bowel preparation not providing sufficient elimination of the intestinal contents and contents therefore being left in the bowel after laxative administration. In addition, a large postoperative fecal volume was considered to occur due to a large amount of watery stool being moved into the rectum upon the release of the stenosis by surgery and the restart of intestinal peristalsis.

Given the above findings, we suggested that appropriate perioperative management for TDT placement was important for ensuring decompression in order to prevent anastomotic leakage during TDT placement. In cases with a large fecal volume from the TDT or intentional defecation, perioperative management should be strictly performed. It is necessary to pay attention not only to instances of fever flare or abdominal pain but also obstruction of the TDT due to bending and unintentional removal of the TDT. Furthermore, adequate bowel preparation should be devised in order to prevent severe watery diarrhea after surgery. Cases with a large tumor diameter in particular were regarded as high-risk cases for a large fecal volume, even if they had no symptom of ileus. In these cases, preoperative treatment, such as dietary restrictions or gradual laxative administration, should be performed to ensure the complete elimination of the intestinal contents.

On the other hand, there was no association between fecal incontinence during TDT placement after surgery and anastomotic leakage. Thus, fecal incontinence during TDT placement was considered to reflect good drainage of the rectum. Thus, the occurrence of fecal incontinence during TDT placement was not associated with a need for increased vigilance.

In the present study, some patients developed anastomotic leakage after the removal of the TDT. These patients developed anastomotic leakage after POD 5, likely due to postoperative factors, such as watery diarrhea. In these cases, the TDT was removed despite drainage by the TDT still being necessary, so frequent defecation occurred after its removal, and anastomotic leakage then developed due to the physical compression of the anastomotic site. Thus, in cases involving a high fecal volume on POD 5, it was suggested that treating the watery diarrhea and delaying the removal of the TDT or the start of meal intake might help prevent anastomotic leakage after the removal of the TDT.

The present study was associated with some limitations. First, this study was a retrospective study that included a relatively small number of patients who were managed at a single institution. As the number of the patients was quite small for statistical analyses, the analysis results may have low reproducibility. Second, the method of bowel preparation and the criteria for removal of the TDT were not uniform and they depended on the choice of each surgeon. Thus, a prospective study should be performed after establishing appropriate criteria, such as the methods of bowel preparation or the timing of removal of the TDT. Third, in Japan, neoadjuvant chemoradiotherapy for locally advanced rectal cancer is not a standard treatment strategy. Considering the effect of radiotherapy at the rectal anastomosis site, patients who had received neoadjuvant chemoradiotherapy were excluded from the present study. When more cases are accumulated, it will be necessary to evaluate the significance of the fecal volume from the TDT in patients who have undergone neoadjuvant chemotherapy as well.

Conclusion

A large fecal volume from the TDT after anterior rectal resection or intentional defecation in patients with TDT placement were suggested to be risk factors for anastomotic leakage. To reduce the rate of anastomotic leakage, it is necessary to perform appropriate bowel preparation and thus reduce the postoperative fecal volume and to provide TDT management for appropriate drainage in the rectum.

Association between anastomotic leakage and the diameter of tumor.

The anastomotic leakage positive group have a significantly longer diameter in comparison to the anastomotic leakage negative group (Median diameter of tumor: 28.0mm; 55.0mm. p = 0.021).

(TIF)

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The receiver operating characteristic curve of the diameter of tumor for anastomotic leakage.

The receiver operating characteristic curve of the diameter of tumor for anastomotic leakage is shown. Area under the curve = 0.760; 95% confidence interval = 0.549–0.892; p = 0.088.

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The receiver operating characteristic curve of the fecal volume from the transanal drainage tube from postoperative days 1–5 for anastomotic leakage during transanal drainage tube placement.

(a) The receiver operating characteristic curve of the maximum daily fecal volume from the transanal drainage tube from postoperative days 1–5 for anastomotic leakage during transanal drainage tube placement is shown. Area under the curve = 0.891; 95% confidence interval = 0.741–0.959; p = 0.054. (b) Receiver operating characteristic curve of the total fecal volume from the transanal drainage tube from postoperative days 1–5 for anastomotic leakage during transanal drainage tube placement is shown. Area under the curve = 0.894; 95% confidence interval = 0.764–0.956; p = 0.152.

(TIF)

Click here for additional data file.

The receiver operating characteristic curve of the fecal volume from the transanal drainage tube on postoperative day 5 for anastomotic leakage after removal of the transanal drainage tube in the subgroup who did not develop anastomotic leakage during TDT placement.

The receiver operating characteristic curve of the fecal volume from the transanal drainage tube on postoperative day 5 for anastomotic leakage after removal of the transanal drainage tube in the subgroup who did not develop anastomotic leakage during TDT placement is shown. Area under the curve = 0.637; 95% confidence interval = 0.267–0.894; p = 0.545.

(TIF)

Click here for additional data file.

24 Feb 2021

PONE-D-20-36803

Significance of information obtained during transanal drainage tube placement after anterior resection of colorectal cancer

PLOS ONE

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Comments to the Author

Reviewer #1: Dear Author. Thanks for your article and precious work. I have some concerns about the methods using for measuring the fecal volume. I dont think if it is possible all fecal volume is passing through tdt. And also in some major studies and metaanalyses fecal volume is not one of the major risk factors. Splenic flexura mobilization, tension free anastamosis with a good blood supply must be the main purposes for a good anastomosis.

Reviewer #2: Page 7, line 4 Comment: 51 patients in 3 years means a low volume for colorectal surgery which is a risk factor for anastomotic leakage.

Page 8, line 9: Did you have the data for the first gas passing in the postoperative period? If yes do you think adding this information may add value to your study?

Page 10, Line 6: 3 patients who had open surgery should be excluded from the study in order to perform a unique evaluation and a more proper statistal analyses.

Page 11, Line 3: What was the preoperative grade of the tumors for the patients? Especially for the LAR group, why did not patients receieved neo-adjuvant chemo-radio therapy?

Table 2: LAR known to be more risky for the anastomotıc leakage. Why the high anterior group had more anastomotic leakage when compared to LAR?

Page 22, line 15: The authors should explain other possible rısk factors. Watery diarrhea should not be the only factor that is emphasized repeatedly.

Page 23, Line 8: Authors should add a paragraph about the relation between BMI and anastomotic leakage to the discussion which is emphasized at the patients characteristics section.

Reviewer #3: MAJOR REVISION

The article describes a technically sound scientific research that will benefit in clinical practice. The manuscript is easy to understand and written in standard English. However, the results are not appropriately drawn based on the data presented. The results of the study was not strongly defended in the discussion. Therefore, my additional recommendations are below:

1. It is unclear how and where (operating room?, postoperatively in the clinic?, colonoscopically?) the pleats drain was inserted. It should be mentioned in more detail in the patients and methods section.

2. In this study, it was stated that TDT is effective in preventing anastomotic leakage. But, it would be more effective to compare the TDT group with a control group without TDT to asses whether it is effectual or not in preventing the leakage.

3. In the study, a single dependent group that received TDT for all cases was analyzed. However, analyzed subgroups do not have the clear definitons in the patients and methods section.

4. It was stated that cases were diveded into “high” and “low” subgroups according to tumor diameters estimated 35 mm cut-off value by the ROC analysis in the results section. Firstly, before calculating the cut-off value and creating subgroups, the relationship between tumor diameter and anastomotic leakage should be demonstrated by correlation tests. If a significant association between them was found, it would be more robust to give the cut-off value by ROC analysis.

5. In the present study involving a single dependent group, patients were divided into the other two subgroups as “high” and “low” according to cut-off value for the fecal volume drained from the TDT, and thus patients were distinguished according to the presence of anastomotic leakage. What should be done before determining a cut-off value and creating subgroups is to demonstrate a significant association between fecal volume and anastomotic leakage by using correlation tests.

6. Table 2 shows the preoperative factors associated with anastomotic leakage. What is the statistical method used here? Were preoperative parameters just compared? Or did multiple factors that may affect anastomotic leakage as the dependent variable analyze?

7. There seems to be a comparison of the anastomotic leakage with different defecation statuses in table 4, which is difficult to understand. According the table 4, why is the total number of patients without fecal incontinence (46 cases) not equal to the total number of patients with intentional defecation (11 cases)?

8. How many of patients had major and minor anastomotic leakage? What is the re-operation rate due to leakage?

9. All patients had the standard mechanical bowel preparation on the day before surgery. So, when did the first defecation postoperatively occur?

10. Leakage was reported in the other 4 of 51 patients after TDT was removed. However, there are again 47 patients in table 6. Where are the remaining 4 patients?

11. The discussion section has generally superficial content. The results of the study were not sufficiently interpreted and discussed. Especially, the association between tumor diameter and fecal volume and its mechanism lack the support of the literature. Therefore, the discussion section should be revised.

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Submitted filename: PONE-D-20-36803_reviewer.pdf

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Submitted filename: Review-Plos One.docx

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28 May 2021

Responses to the reviewer’s comments

We wish to express our appreciation to the reviewers for their insightful comments, which have helped us significantly improve the paper.

Reviewer 1

Reviewer #1: Dear Author. Thanks for your article and precious work. I have some concerns about the methods using for measuring the fecal volume. I dont think if it is possible all fecal volume is passing through tdt. And also in some major studies and metaanalyses fecal volume is not one of the major risk factors. Splenic flexura mobilization, tension free anastamosis with a good blood supply must be the main purposes for a good anastomosis.

Response: As you pointed out, splenic flexura mobilization of the colon or tension-free anastomosis with a good blood supply is important for preventing anastomotic leakage. Therefore, in our facility, we mobilize the descending colon sufficiently and add mobilization of the splenic flexura as needed while confirming a good blood supply to the anastomosis by fluorescence imaging with indocyanine green. In the present study, we did not intend for TDT management to be the only method for preventing anastomotic leakage. We reported the significance of TDT management in addition to these already known methods to prevent anastomotic leakage.

In previous papers, postoperative diarrhea has been reported as a risk factor of anastomotic leakage. However, only a few reports have explored whether or not the fecal volume is a risk factor. In two meta-analyses, the fecal volume was not evaluated as a risk factor of anastomotic leakage, so whether or not the postoperative fecal volume is a major risk factor is unclear. TDT placement has facilitated the evaluation of the postoperative fecal volume in recent years. Therefore, we investigated whether or not the postoperative fecal volume through the TDT was a risk factor of anastomotic leakage.

The TDT was connected to the closed bag immediately after surgery, thus allowing the fecal volume through the TDT to be measured exactly. While measuring the fecal volume that did not pass through the TDT was difficult and the exact fecal volume in the rectum was not measured, we investigated the occurrence of intentional defecation or fecal incontinence as an alternative to determine the unmeasurable fecal volume. We evaluated the associations between anastomotic leakage and intentional defecation/fecal incontinence.

Reviewer 2

Q1. Page 7, line 4 Comment: 51 patients in 3 years means a low volume for colorectal surgery which is a risk factor for anastomotic leakage.

Response: As you pointed out, our total of 51 patients was quite small for the number of cases expected to be accumulated over 3 years. We considered it important to minimize the variation in the patient background. Therefore, the following patients were excluded from this study: those who underwent emergency operation, those who underwent NACRT, those who had ileus before surgery, those operated with an anastomosis method other than DST, those who received diverting stoma and those whose TDT was removed during PODs 1-4. After excluding the above patients, we were left with only 51 target patients, all of who showed little variation in their background.

Q2. Page 8, line 9: Did you have the data for the first gas passing in the postoperative period? If yes do you think adding this information may add value to your study?

Response: As the gas during TDT placement was basically drained through the TDT, the date of the first postoperative gas passage could not be determined. It is thus difficult to add these data to the manuscript.

Q3. Page 10, Line 6: 3 patients who had open surgery should be excluded from the study in order to perform a unique evaluation and a more proper statistal analyses.

Response: The fecal volume from the TDT did not markedly differ between laparoscopic and open surgery (P20 Table6 in the revised manuscript). In addition, had we excluded the two open surgery cases, the sample size in this study would have been even smaller. We therefore feel that these cases should not be excluded.

Q4. Page 11, Line 3: What was the preoperative grade of the tumors for the patients? Especially for the LAR group, why did not patients receieved neo-adjuvant chemo-radio therapy?

Response: We have now added the pathological T/N factors of the patients to Tables 1 and 2. The pathological T stage of 47 patients was T1-3, and that of 4 patients was T4. The pathological N stage of 43 patients was N0, and that of 8 patients was N1-3. The anastomotic leakage rate was not significantly higher in the groups with T4 or N1-3 than in the other groups. Please confirm the revised manuscript (P10-13 patient characteristics, Table 1 and 2 in the revised manuscript). We have also added the No23 reference.

In Japan, neoadjuvant chemoradiotherapy (NACRT) for locally advanced rectal cancer is not a standard treatment strategy. While NACRT is occasionally performed, we create diverting stomas in such cases. Patients who received NACRT were therefore excluded in this study. We have now mentioned this in the limitations section; please confirm the revised manuscript. (P27 lines11-16)

Q5. Table 2: LAR known to be more risky for the anastomotıc leakage. Why the high anterior group had more anastomotic leakage when compared to LAR?

Response: In the present study, the anastomotic leakage rate was higher in patients who underwent LAR than in those who underwent HAR. Please see Table 2 in our manuscript (P12).

Q6. Page 22, line 15: The authors should explain other possible rısk factors. Watery diarrhea should not be the only factor that is emphasized repeatedly.

Response: The correlations between the preoperative factors and anastomotic leakage in the present study are shown in Table 2, and the correlations between the risk factors of anastomotic leakage and fecal volume from the TDT are shown in Table 5 (P20 Table 6 in the revised manuscript). However, we did not present the results of the multivariate analysis for risk factors of the four anastomotic leakage incidents that occurred during TDT placement. The multivariate analysis indicated that a large tumor diameter and large total fecal volume from the TDT during the first 5 postoperative days were independent risk factors for anastomotic leakage during TDT placement. We have now mentioned these findings in the manuscript. Please see Table 5 in the revised manuscript (P19).

Q7. Page 23, Line 8: Authors should add a paragraph about the relation between BMI and anastomotic leakage to the discussion which is emphasized at the patients characteristics section.

Response: While a few reports have described the correlation between the BMI and anastomotic leakage, the mechanism underlying the correlation has been unclear, and the evidence level has been low. In the present study, no correlation between the BMI and anastomotic leakage was noted, so we omitted the details of this examination.

Reviewer 3

MAJOR REVISION

The article describes a technically sound scientific research that will benefit in clinical practice. The manuscript is easy to understand and written in standard English. However, the results are not appropriately drawn based on the data presented. The results of the study was not strongly defended in the discussion. Therefore, my additional recommendations are below:

Response: Thank you for your constructive comment. We performed a deeper investigation and revised our manuscript as shown below.

Q1. It is unclear how and where (operating room?, postoperatively in the clinic?, colonoscopically?) the pleats drain was inserted. It should be mentioned in more detail in the patients and methods section.

Response: In our study, all of the TDTs were placed at the last step of the colorectal cancer operation under general anesthesia. We have now mentioned this in the Methods section (P8 lines8-9). Please confirm the revised manuscript.

Q2. In this study, it was stated that TDT is effective in preventing anastomotic leakage. But, it would be more effective to compare the TDT group with a control group without TDT to asses whether it is effectual or not in preventing the leakage.

Response: We began placing TDTs for all patients from January 2016. Before January 2016, TDT placement was only performed for patients considered to be at high risk of anastomotic leakage by the surgeon. In addition, the kind of TDT was not unified. Therefore, selection bias likely occurred, making it difficult to adequately prove the usefulness of a TDT for preventing anastomotic leakage based on an analysis of our hospital data.

Based on the premise outlined in previous reports that TDTs were effective for preventing anastomotic leakage after rectal cancer, we evaluated the correlation between anastomotic leakage and the fecal volume from the TDT.

Q3. In the study, a single dependent group that received TDT for all cases was analyzed. However, analyzed subgroups do not have the clear definitons in the patients and methods section.

Response: In the Methods section, we have defined a subgroup of patients in whom no anastomotic leakage occurred after TDT placement (P9 lines6-9). Please confirm the revised manuscript.

Q4. It was stated that cases were diveded into “high” and “low” subgroups according to tumor diameters estimated 35 mm cut-off value by the ROC analysis in the results section. Firstly, before calculating the cut-off value and creating subgroups, the relationship between tumor diameter and anastomotic leakage should be demonstrated by correlation tests. If a significant association between them was found, it would be more robust to give the cut-off value by ROC analysis.

Response: We have now added a new figure and explanation concerning the correlation between a large tumor diameter and anastomotic leakage before the ROC analysis. The tumor diameter in the patients who experienced anastomotic leakage was significantly greater than that in the patients without anastomotic leakage. Please confirm S1 Figure in the revised manuscript (P37).

Q5. In the present study involving a single dependent group, patients were divided into the other two subgroups as “high” and “low” according to cut-off value for the fecal volume drained from the TDT, and thus patients were distinguished according to the presence of anastomotic leakage. What should be done before determining a cut-off value and creating subgroups is to demonstrate a significant association between fecal volume and anastomotic leakage by using correlation tests.

Response: We have now added a new figure and explanation concerning the correlation between the fecal volume from the TDT and anastomotic leakage before the ROC analysis. The maximum fecal volume from the TDT during POD 1-5 in patients who experienced anastomotic leakage during TDT placement was significantly greater than that in patients without anastomotic leakage during TDT placement (Fig. 1a). The total fecal volume from the TDT during POD 1-5 in patients who experienced anastomotic leakage during TDT placement was significantly greater than that in patients without anastomotic leakage during TDT placement (Fig. 1b). Please confirm the revised manuscript (P15 lines 10-18).

Q6. Table 2 shows the preoperative factors associated with anastomotic leakage. What is the statistical method used here? Were preoperative parameters just compared? Or did multiple factors that may affect anastomotic leakage as the dependent variable analyze？

Response: Table 2 shows the difference in the background characteristics between the anastomotic leakage-positive group and the anastomotic leakage-negative group. However, this result alone was not enough to exclude confounding factors when risk factors for anastomotic leakage during TDT placement were evaluated.

Therefore, we performed a multivariate analysis of the risk factors of anastomotic leakage during TDT placement. We have now added a new table and appropriate explanation. The multivariate analysis indicated that a large tumor diameter and large total fecal volume from the TDT during the first 5 postoperative days were independent risk factors for anastomotic leakage during TDT placement (P19 Table 5 in the revised manuscript). Please confirm the revised manuscript.

Q7. There seems to be a comparison of the anastomotic leakage with different defecation statuses in table 4, which is difficult to understand. According the table 4, why is the total number of patients without fecal incontinence (46 cases) not equal to the total number of patients with intentional defecation (11 cases)?

Response: In this study, the defecation of watery stool which did not pass through the TDT occurred in 16 of 51 patients in spite of TDT placement after surgery. Of the 16 patients, 11 had intentional defecation, and 5 had fecal incontinence. There was no overlap between the 11 patients and the 5 patients. We evaluated the correlation between anastomotic leakage and intentional defecation in the 11 positive and 40 negative patients and the correlation between anastomotic leakage and fecal incontinence in the 5 positive and 46 negative patients.

Q8. How many of patients had major and minor anastomotic leakage? What is the re-operation rate due to leakage?

Response: In the present study, of the eight instances of anastomotic leakage, major leakage occurred in two patients, and minor leakage occurred in six patients. Re-operation for anastomotic leakage was performed in the 2 major leakage patients (3.9%). Of the four anastomotic leakages during TDT placement, major leakage occurred in two patients, and minor leakage occurred in two patients. All instances of anastomotic leakage after TDT removal were minor leakages. We have now mentioned this in the Results section of the revised manuscript (P13 lines 5-10).

Q9. All patients had the standard mechanical bowel preparation on the day before surgery. So, when did the first defecation postoperatively occur?

Response: We found it difficult to define the first defecation, as all of the patients had TDTs placed for at least the first 5 postoperative, and watery stool was drained through the TDT. The first defecation, which we defined as ‘intentional defecation’ during TDT placement, occurred in two patients on POD 1, four patients on POD 2, one patient on POD 3, two patients on POD 4 and one patient on POD 5.

Q10. Leakage was reported in the other 4 of 51 patients after TDT was removed. However, there are again 47 patients in table 6. Where are the remaining 4 patients?

Response: Table 6 (Table 7 in the revised manuscript) shows the results of the subgroup analysis for 47 patients, excluding the 4 with anastomotic leakage during TDT placement. Please confirm the Methods section of the manuscript (P9 lines6-9).

Q11. The discussion section has generally superficial content. The results of the study were not sufficiently interpreted and discussed. Especially, the association between tumor diameter and fecal volume and its mechanism lack the support of the literature. Therefore, the discussion section should be revised.

Response: We have now added a comment concerning the association between the tumor diameter and fecal volume in the Discussion (p25 lines9-14) as follows:

“[…] a large tumor can cause stenosis of the bowel, resulting in bowel preparation not providing sufficient elimination of the intestinal contents and contents therefore being left in the bowel after laxative administration. In addition, a large postoperative fecal volume was considered to occur due to a large amount of watery stool being moved into the rectum upon the release of the stenosis by surgery and the restart of intestinal peristalsis.”

Again, we appreciate all the insightful comments. Thank you for taking the time and energy to help us improve the paper.

Submitted filename: Response to Reviewers.docx

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4 Jul 2022

Significance of information obtained during transanal drainage tube placement after anterior resection of colorectal cancer

PONE-D-20-36803R1

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18 Aug 2022

PONE-D-20-36803R1

Significance of information obtained during transanal drainage tube placement after anterior resection of colorectal cancer

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