Surgery for colorectal cancer (CRC) has a high risk of morbidity (20%–40%) and mortality (1%–2%) [
Many host- and disease-related factors have been studied, and some of them are supposed to be predictive for occurrence of SSI. Obesity is a commonly reported risk factor for the development of SSI [
Preoperative anemia (POA) is very common in CRC patients. It has been reported that the prevalence of POA is as high as 23.23% in Chinese CRC patients [
We retrospectively collected the clinical data of 405 patients who underwent elective colorectal surgery for pathologically confirmed colorectal cancer from January 2011 to December 2013 at the department of general surgery, the First Hospital Affiliated to the University of Science and Technology of China in China. This study is approved by the Ethical Committee of Anhui Provincial Hospital.
Eligible criteria for patient selection included pathologically conformed colorectal cancer and undergoing electively palliative or curative colorectal resection. Exclusion criteria were receiving preoperative chemoradiotheray (
All patients received prophylactic antibiotics according to the guideline for clinical application of antimicrobial agents in China [
We collected the following information from medical records: patients’ age, gender, BMI, preoperative Hb, location of cancer (colon or rectum), American Society of Anesthesiologist (ASA) classification, preoperative comorbidity, abdominal surgical history, operative time, estimated blood loss, RBC (red blood cells) transfusion, surgical types (laparoscopy or open surgery), surgical procedure (colon or rectal resection), stoma formation, tumor diameter, and TNM stage. Patients were pathologically categorized by the 7th AJCC/TNM staging system (American Joint Committee on Cancer (AJCC)) [
POA was defined by a Hb level < 12 g/dl [
The primary endpoint was surgical site infection (SSI) rate within 30 days after surgery. SSI was defined by the Center for Disease Control and Definition ((CDC)
Secondary endpoint included surgically related and systemic complications that occurred within 30 days after surgery. Surgically related complications included the complications directly caused by surgery, including bleeding, anastomotic leak, small bowel obstruction, ileus, and stoma stenosis. Systemic complications included pulmonary, cardiac, urinary tract, and neurological problems. There was no death for all patients.
Data were shown as proportion or median (25% quartile–75% quartile). Continuous data was compared using the Mann–Whitney
Among 326 patients with pathologically confirmed CRC, 154 patients (47.2%) were diagnosed with POA. The characteristics of included patients were shown in Table
Preoperative variables.
Clinical features | Total ( |
Anemia group ( |
Nonanemia group ( |
|
---|---|---|---|---|
Patients | 326 | 154 | 172 | |
Age (years) | 0.20 | |||
≤65 years | 197 (60%) | 87 (57%) | 110 (64%) | |
>65 years | 129 (40%) | 67 (43%) | 62 (36%) | |
Gender (male/female) | <0.01 | |||
Males | 191 (59%) | 61 (40%) | 130 (73%) | |
Females | 135 (41%) | 93 (60%) | 42 (27%) | |
BMI (kg/m2) | 0.14 | |||
<25 | 285 (87%) | 139 (90%) | 146 (85) | |
≥25 | 41 (13%) | 15 (10%) | 26 (15%) | |
RBC (×1012/L)† | 4.2 (3.8–4.6) | 3.8 (3.5–4.0) | 4.5 (4.3–4.7) | <0.01 |
Hemoglobin (HB, g/dl) | 12.1 (10.4–13.5) | 10.4 (9.1–11.2) | 13.4 (12.7–14.3) | <0.01 |
Location of cancer | <0.01 | |||
Colon | 141 (43%) | 93 (60%) | 38 (22%) | |
Rectum | 195 (57%) | 61 (40%) | 134 (78%) | |
ASA classification | 0.13 | |||
ASA-1/2 | 309 (6%) | 149 (97%) | 160 (93%) | |
ASA-3 | 17 (89%) | 5 (3%) | 12 (7%) | |
Comorbidities | ||||
Hypertension | 75 (23%) | 48 (31%) | 27 (16%) | <0.01 |
Diabetes | 30 (9%) | 16 (10%) | 13 (7%) | 0.47 |
Cardiac diseases | 14 (4%) | 9 (6%) | 5 (3%) | 0.19 |
Respiratory diseases | 12 (4%) | 4 (3%) | 8 (5%) | 0.33 |
Renal diseases | 2 (0.6%) | 1 (0.7%) | 0 (0%) | 0.47 |
Cerebral diseases | 7 (2%) | 4 (3%) | 3 (2%) | 0.71 |
Abdominal surgical history | 54 (17%) | 25 (16%) | 29 (17%) | 0.52 |
†RBC: red blood cells.
POA patients received more RBC transfusion than those without POA (25.9% versus 1.7%,
Intraoperative variables.
Anemia group ( |
Nonanemia group ( |
||
---|---|---|---|
Operative time | 140 (120–180) | 138 (115–180) | 0.90 |
Estimated blood loss | 100 (80–150) | 100 (50–150) | 0.41 |
Perioperative RBC transfusion, |
40 (25.9%) | 3 (1.7%) | <0.01 |
Units of RBC transfusion | 3 (2–6) | 4 (2–4) | <0.01 |
Types of operation, | <0.01 | ||
Laparoscopic surgery† | 60 (39%) | 109 (63%) | |
Open surgery | 94 (61%) | 63 (37%) | |
Surgical procedure, | <0.01 | ||
Colon resection | 93 (60%) | 38 (22%) | |
Rectum resection | 61 (40%) | 135 (78%) | |
Stoma formation, |
36 (23%) | 51 (30%) | 0.20 |
Maximum diameter of cancer (cm) | 0.02 | ||
<4 cm | 47 (31%) | 75 (44%) | |
≥4 cm | 107 (69%) | 97 (56%) | |
T stage, | 0.25 | ||
T1 | 4 (3%) | 6 (4%) | |
T2 | 19 (12%) | 35 (20%) | |
T3 | 98 (64%) | 98 (57%) | |
T4 | 33 (21%) | 33 (19%) | |
Number of nodal harvest | 9 (6–12) | 7 (4–11) | <0.01 |
Patients with nodal metastasis, |
52 (34%) | 70 (41%) | 0.31 |
TNM stage, | 0.58 | ||
I/II | 96 (62%) | 102 (59%) | |
III/IV | 58 (38%) | 70 (41%) |
†Included laparoscopy-assisted and hand-assisted laparoscopic colorectal resection for colorectal cancer (CRC).
Compared to patients without POA, patients with POA had a higher risk of incisional SSI (12% versus 6%,
Postoperative complications between POA and non-POA patients.
POA group ( |
Non-POA group ( |
||
---|---|---|---|
SSI† | 19 (12%) | 13 (8%) | 0.15 |
Incisional SSI | 19 (12%) | 10 (6%) | 0.04 |
Organ space SSI | 4 (3%) | 6 (3%) | 0.75 |
Ileus | 3 (2%) | 6 (3%) | 0.51 |
Small bowel obstruction | 1 (1%) | 0 (0%) | 0.47 |
Anastomotic leakage | 3 (2%) | 5 (3%) | 0.73 |
Bleeding | 2 (1%) | 3 (2%) | 1.00 |
Stoma stenosis | 2 (1%) | 4 (2%) | 0.69 |
Pulmonary problem | 4 (3%) | 2 (1%) | 0.43 |
Cardiac problem | 1 (1%) | 0 (0%) | 0.47 |
Urinary problem | 1 (1%) | 3 (2%) | 0.63 |
Neurologic problem | 0 (0%) | 0 (0%) | NA |
Others | 2 (1%) | 1 (1%) | 0.60 |
Reoperation | 3 (2%) | 7 (4%) | 0.35 |
Postoperative death | 0 (0%) | 0 (0%) | NA |
Number of complications¶ | 47 (31%) | 32 (19%) | |
1 | 20 (13%) | 26 (15%) | 0.58 |
2 | 3 (2%) | 4 (2%) | 1.00 |
3 or more | 3 (2%) | 2 (1%) | 0.67 |
Infectious complications | 23 (15%) | 20 (12%) | 0.39 |
Postoperative hospitalization | 8 (7–10) | 9 (8–11) | 0.14 |
†SSI: surgical site infection; ¶Number of complications, per patient with the number of complications after surgery; POA: preoperative anemia; NA: not available.
Upon univariable analysis, POA and stoma formation were significantly associated with increased risk of incisional SSI (
Univariable analysis of factors linked to incisional SSI†.
Incisional SSI ( |
No incisional SSI ( |
|||
---|---|---|---|---|
Patients ( | 29 | 297 | ||
POA | Yes | 19 (66%) | 135 (46%) | 0.04 |
No | 10 (34%) | 162 (54%) | ||
RBC transfusion | Yes | 3 (10%) | 33 (11%) | 0.90 |
No | 26 (90%) | 264 (89%) | ||
Age | ≤65 years | 16 (55%) | 181 (61%) | 0.54 |
>65 years | 13 (45%) | 116 (39%) | ||
Gender | Males | 18 (62%) | 173 (58%) | 0.69 |
Females | 11 (38%) | 124 (42%) | ||
BMI | <25 kg/m2 | 23 (79%) | 262 (88%) | 0.17 |
≥25 kg/m2 | 6 (21%) | 35 (12%) | ||
Location of cancer | Colon | 9 (31%) | 122 (41%) | 0.29 |
Rectum | 20 (69%) | 175 (59%) | ||
ASA classification | ASA-1/2 | 27 (93%) | 282 (95%) | 0.67 |
ASA-3 | 2 (7%) | 15 (5%) | ||
Hypertension | Yes | 8 (28%) | 67 (23%) | 0.54 |
No | 21 (72%) | 230 (77%) | ||
Diabetes | Yes | 2 (7%) | 28 (9%) | 0.65 |
No | 27 (93%) | 269 (91%) | ||
Cardiac diseases | Yes | 2 (7%) | 13 (4%) | 0.54 |
No | 28 (93%) | 284 (96%) | ||
Respiratory diseases | Yes | 0 (0%) | 12 (4%) | 0.27 |
No | 29 (100%) | 285 (96%) | ||
Renal diseases | Yes | 1 (4%) | 0 (0%) | 0.09 |
No | 28 (96%) | 296 (100%) | ||
Cerebral diseases | Yes | 0 (0%) | 7 (2%) | 1.00 |
No | 29 (100%) | 290 (98%) | ||
Abdominal surgical history | Yes | 7 (24%) | 47 (16%) | 0.25 |
No | 22 (76%) | 250 (84%) | ||
Types of operation | Laparoscopic surgery | 15 (52%) | 154 (36%) | 0.75 |
Open surgery | 14 (48%) | 163 (64%) | ||
Stoma formation | Yes | 12 (41%) | 24 (8%) | <0.01 |
No | 17 (59%) | 273 (92%) | ||
Surgical resection | Colon resection | 8 (28%) | 123 (41%) | 0.15 |
Rectum resection | 21 (72%) | 174 (59%) | ||
Cancer size(cm) | <4 | 9 (31%) | 113 (38%) | 0.46 |
≥4 | 20 (69%) | 184 (62%) | ||
T stage | T1/T2 | 7 (24%) | 57 (19%) | 0.52 |
T3/T4 | 22 (76%) | 240 (81%) | ||
AJCC-TNM stage | I/II | 22 (76%) | 176 (59%) | 0.08 |
III/IV | 7 (24%) | 121 (41%) |
†SSI: surgical site infection.
Multivariate analysis of risk factors linked to incisional SSI.
OR | 95%CI | ||
---|---|---|---|
Anemia (yes versus no) | 0.03 | 2.44 | 1.09–5.49 |
Stoma formation (yes versus no) | 0.02 | 2.64 | 1.20–5.81 |
High prevalence of anemia has been reported in surgical patients, and POA has been proved to increase occurrences of postoperative mortality and complications in cardiac, gastric and esophageal surgery [
The prevalence of POA greatly varies in CRC patients due to different locations of cancer lesion. Overall rate of CRC-related anemia ranges from 20% to 50% [
Multiple factors contribute to the incidence of cancer-related anemia in CRC patients. Chronic blood loss from tumor mass is the important reason for cancer-related anemia, because cancer patients with anemia always show significantly higher ferritin and hepcidin levels than general peoples, which suggests iron deficiency in these patients [
High prevalence of POA causes great attention of surgeons, and many clinical studies have been conducted to investigate its impact on surgical recovery [
Although increasing evidence suggested that POA was associated with poor outcomes after surgery [
The present study has some limitations. First, this study is retrospective and encounters some inherent bias. In addition, this study could not determine the causality of POA in incisional SSI for CRC patients. Therefore, prospective studies are necessary in the future. Second, the effects of some unknown or unmeasured confounders on the association between POA and incisional SSI could not be ruled out. However, owing to the robust results of this study, it seems that confounding factors that were not included in analysis were unlike to change the results.
In summary, this study suggested that POA (Hb < 12 g/dL) was associated with an increased risk of incisional SSI after elective CRC surgery, and correcting preoperative anemia before surgery should be considered. Prospective high-quality studies were needed to confirm our findings in the future.
All authors declare no conflict of interest.
Liu Liu, Lin Liu, and Zhiqiang Zhu did the study conception and design; Liu Liu and Xiao Wan did the acquisition of data; Liu Liu, Lin Liu, and Qiang Huang did the analysis and interpretation of data; Liu Liu, Lichuan Liang, and Hengbing Dai did the drafting of the manuscript; Lin Liu and Zhiqiang Zhu did the critical revision.
This study was funded by the National Natural Science Foundation of China (81501601) and Natural Science Foundation of Anhui Province of China (1608085QH198).