From January 2013 to December 2016, 480 out of 915 patients met the inclusion criteria (Fig. 1), all with CRC and operated in the Colorectal Unit at the Leiria Central Hospital. We excluded procedures for benign disease (n = 243; 26.6%), without anastomosis (n = 72; 7.9%) and for stoma closure (n = 65; 7.1%). Pouch surgery, reintervention or small bowel resection were also not considered.
This cohort (N = 480) is composed mostly by men (n = 287; 59.8%), with colon cancer (n = 353; 73,5%) and a mean age of 70.4 ± 12.57 years. Thirty-seven patients developed AL (7.7%) and the rate decreased gradually each year, from 9.1% in 2013 to 5% in 2016 (Fig. 2). Anastomotic leak was more frequent in men (n = 26; 70.3%), left colectomy and proctectomy (n = 25; 67.5%) and in the laparotomic approach (n = 13; 35.1%) or conversion (n = 5; 13.5%). Clinical characteristics and different surgical approaches are summarised in Tables 1 and 2.
Table 1
– Cohort demographic and clinical characteristics (Leak vs. No leak groups).
|
NO ANASTOMOTIC LEAKAGE (AL)
(N = 443; 92.3%)
|
ANASTOMOTIC LEAKAGE
(N = 37; 7.7%)
|
P VALUE (95% CI)
|
AGE (Mean ± SD)
|
70.25 ± 12.61
|
72.1 ± 12.05
|
0.390 (-2.4 to 6.1)
|
SEX (M/F)
|
261 (58.9%) /182 (41.1%)
|
26 (70.3%) / 11 (29.7%)
|
0.175 (-5.3 to 24.5)
|
ASA SCORE
I – II
III – IV
|
270 (60.9%)
173 (39.1%)
|
24 (64.9%)
13 (35.1%)
|
0.632 (-12.7 to 18.1)
|
STAGE
I
II
III
IV
|
148 (33.4%)
127 (28.7%)
126 (28.4%)
42 (9.5%)
|
9 (24.4%)
13 (35.1%)
12 (32.4%)
3 (8.1%)
|
0.263 (-7.4 to 20.9)
0.411 (-7.6 to 22.9)
0.606 (-9.5 to 20.6)
|
COMORBIDITY
< 2
2 or more
|
350 (79%)
93 (21%)
|
32 (86.5%)
5 (13.5%)
|
0,226 (-6.4 to 17.1)
|
Table 2
Cohort demographic and clinical characteristics (Leak vs. No leak groups).
|
NO ANASTOMOTIC LEAKAGE
NO AL
(N = 443; 92.3%)
|
ANASTOMOTIC LEAKAGE
AL
(N = 37; 7.7%)
|
P VALUE (95% CI)
|
TIMING
Elective
Urgent
|
363 (81.9%)
80 (18.1%)
|
30 (81.1%)
7 (18.9%)
|
0.909 (-9.4 to 16.4)
|
APPROACH
Open
Laparoscopic
Conversion
|
97 (21.9%)
333 (75.2%)
13 (2.9%)
|
13(35.1%)
19 (51.4%)
5 (13.5%)
|
0.067 (-0.7 to 16.7)
0.002 (8.0 to 39.7)
|
PROCEDURES
Right
Left
Rectum
Others
|
202 (45.6%)
128 (28.9%)
84 (19.0%)
28 (6,5%)
|
10 (27.0%)
13 (35.1%)
12(32.4%)
2 (5.5%)
|
0.003 (2.0 to 15.9)
0.427 (-7.1 to 22.8)
0.050 (0.0 to 29.9)
|
COVERING STOMA
Yes
No
|
53 (11.9%)
390 (88.1%)
|
10 (27.1%)
27 (72.9%)
|
0.008 (3.1 to 31.4)
|
Thirty-two patients (86.5%) had AL diagnosis at the first hospital admission and five had the diagnosis deferred. Mean time for AL detection was 6.8 days (day 2 to 17) and was most common on day 5. Twenty-five patients were diagnosed based on clinical criteria, including biomarkers (leukocyte and C-Reactive Protein) having the diagnosis taken place earlier in this sub-group of patients (5.6 ± 2.1 days). These patients had a shorter LOHS (26.1 vs. 40.9 days), which is not statistically significant [(p = 0.073; 95% CI (-1.0 to 34)]. The remaining twelve required additional exams, such as abdomen-pelvic CT scan and/or lower GI endoscopy. CT imaging did not show unequivocal signs of AL in 3 (25%) of the 12 patients scanned. Diagnosis was reached later (8.5 ± 4.2 days), with statistical significance [p = 0.004; 95% CI (0.7 to 4.8)] – Tables 3 and 4.
Table 3
AL DIAGNOSIS
|
• TIMING (Days):
• Mean (SD)
• Median
• Mode
|
6.8 (2.2)
6
5
|
• 1ST EPISODE - N (%)
|
32 (86.5%)
|
• DEFERRED (Readmission) - N (%)
|
5 / (13.5%)
|
Table 4
|
CLINIC (BIOMARKERS/ REOPERATION)
(N = 25; 64.9%)
|
OTHERS
(CT SCAN ± ENDOSCOPY)
(N = 12; 35.1%)
|
P VALUE (95% CI)
|
TIMING – Days
Mean ± SD
Median
Max
Min
|
5.7 ± 2,1
5
7
3
|
8.5 ± 4.2
8
21
4
|
0.004
(0.7 to 4.8)
|
LOHS – Days
Mean ± SD
Median
Max
Min
|
26.1 ± 10.9
21
97
15
|
40.9 ± 41.5
38
165
23
|
0.073
(-1.0 to 34)
|
Six patients were managed non-operatively and four needed an image-guided drainage of intraabdominal collections (one by transrectal access). Twenty-four out of 31 patients (64.8%) were submitted to anastomotic takedown and Hartmann’s procedure, and six (16.2%) underwent refashion of the anastomosis with covering stoma. Twelve (32.4%) out of the 37 patients required ICU admission and fifteen (40.5%) received parenteral nutrition. Over 34.9 months of follow up, 20 out of 37 patients (54.1%) maintained bowel continuity, including preserved primary or refashioned anastomosis (n = 10; 27%) and Hartmann reversal status (n = 10; 27%). The main causes for not closing the stoma were patient refusal and morbidity (n = 10) and cancer dissemination (n = 4). The causes for secondary anastomotic failure were stenosis (n = 2) and local recurrence (n = 1) - Fig. 3.
Concerning morbidity, the rate of complications was significantly higher in the AL-patient group. Based on the Clavien-Dindo classification, 26 out of the 37 patients (70.2%) had grade III and IV complications, vs. 34 patients in the group who had no AL (7.7%) (Table 5). Mean LOHS was significantly higher in the AL cohort [(10.5 vs. 31.3 days - < 0.0005 (14.9 to 21.9)].
Table 5
Postoperative complications according to the Clavien-Dindo classification (Leak vs. No leak group).
|
NO ANASTOMOTIC LEAKAGE (AL)
(N = 443; 92.3%)
|
ANASTOMOTIC LEAKAGE
(N = 37; 7.7%)
|
P VALUE (95% CI)
|
LOHS – days
Mean (range)
Median
|
10.5 (3-138)
7
|
31.3 (15–165)
27
|
< 0.0005 (14.9 to 21.9)
|
MORBIDITY – n (%)
Clavien-Dindo I
Clavien-Dindo II
Clavien-Dindo III
Clavien-Dindo IV
|
39 (8.8 %)
47 (10.6 %)
16 (3.6%)
18 (4.1 %)
|
2 (5.4%)
1 (2.7%)
18 (48.6 %)
8 (21.6%)
|
0.395 (-5.8 to 9)
0.059 (-0.3 to 11.3)
< 0.0005 (30.2 to 59.5)
< 0.0005 (8.5 to 34.5)
|
REOPERATION – n (%)
(W/in 12 months)
|
27 (6.1%)
|
31 (83.8%)
|
< 0.0005 (6 to 89.4)
|
30-DAY MORTALITY – n (%)
Elective
Overall
|
8 (1.8 %)
21 (4.7 %)
|
5 (13.5 %)
8 (21.6 %)
|
< 0.0005 (5.1 to 26.9)
< 0.0005 (8.1 to 32.9)
|
FOLLOW-UP - months
|
35.7
|
34.9
|
0.818 (-4.7 to 3.9)
|
In the first year, need for reoperation and 30-day mortality were more significant in AL-patient group, 83.8% vs. 6.1% (p < 0.0005; 95%CI 6 to 89.4) and 21.6% vs. 4.7% (p < 0.0005; 95%CI 8.1 to 32.9), respectively. Considering the elective cohort, 30-day mortality rate was higher in the AL group (13.5% vs. 1.8%). Furthermore, mortality was lower in the second biennium (2015-16) in both groups (with and without AL), 27.2% vs. 15.5% (p = 0.417; 95%CI -17.6 to 34.9) and 6.1% vs. 2.3% (p = 0.049; 95%CI – 0.1 to 7.8), respectively.
Concerning the impact of AL on the overall survival (OS), with an average follow-up of 47.4 ± 23.2 months, patients without AL had a 5-year OS (in all stages) of 63.3%, versus 52.9% in the AL-patients group. Comparing Kaplan-Meier's survival curves, the Gehan-Breslow-Wilcoxon test shown statistical significance in OS between the groups (50 ± 6.6 vs. 62.4 ± 1.5 months; p = 0.009) – Fig. 4.
Regarding the morbidity analysis, the 5-year OS was 55.6, 50, 63.6 and 0% for the patient group with AL complications, versus 76.3, 69.7, 59.7 and 10.5% in the patient group without AL. Comparing Kaplan-Meier's survival curves, the Gehan-Breslow-Wilcoxon test shown significant differences in survival time between the two groups (p = 0.005), at the different stages (Fig. 5).
Colon cancer patients who developed AL had a significant lower 5-year OS, 50%, versus 66.3% (p = 0.002). This significant difference was not observed in the AL rectal cancer cohort, as the 5-year OS was 55.6% versus 65%, in the no-AL cohort (p > 0.05) - (Fig. 6).