Impact of Pre-Storage and Bedside Filtered Leukocyte-Depleted Blood Transfusions on Infective Morbidity after Colorectal Resection: A Single-Center Analysis of 437 Patients

Abstract

Background:

Leukocyte-depleted blood transfusions were introduced to reduce transfusion-associated immunomodulation, but the clinical effects of different types of leukocyte depletion have been analyzed rarely. The aim of this survey was to analyze the clinical impact of pre-storage leukocyte-depleted blood transfusions (considered as pre-storage or bedside-filtered) on post-operative complications in patients undergoing elective or urgent colorectal resection.

Methods:

Data were collected retrospectively from the medical records of 437 consecutive patients who underwent colorectal resection from 2005 to 2010. All patients requiring transfusion received pre-storage or bedside-filtered leukocyte-depleted red blood cell concentrates according to availability at the blood bank. The outcomes were measured by the analysis of post-operative morbidity in patients receiving the different types of transfusions or having other potentially predictive risk factors.

Results:

The overall morbidity rate, infective morbidity rate, and non-infective morbidity rate were, respectively, 35.6%, 28.1%, and 21.0%. Two hundred five patients (46.9%) received peri-operative transfusions. On multivariable analysis, leukocyte-depleted transfusion (odds ratio [OR] 3.33; 95% confidence interval [CI] 2.14–5.20; p<0.001) and both pre-storage (OR 2.82; 95% CI 1.73–4.59; p<0.001) and bedside-filtered (OR 4.69; 95% CI 2.54–8.67; p<0.001) transfusions were independent factors for post-operative morbidity. Prolonged operation (p=0.035), American Society of Anesthesiologists score≥3 points (p=0.023), diagnosis of cancer rather than benign disease (p=0.022), and urgent operation (p=0.020) were other independent predictors of post-operative complications. Patients transfused with bedside-filtered blood showed significantly higher rates of infective complications (51.4% vs. 31.8%; p=0.006), but not non-infectious complications (35.7% vs. 32.6; p=0.654) than patients who received pre-storage transfusions.

Conclusions:

Leukocyte-depleted blood transfusions and, in particular, bedside-filtered blood have a significant negative effect on infectious complications after colorectal resection.

Colorectal surgery is associated with substantial postoperative morbidity rates, ranging from 17.7% to 37.2% in the general population and even greater in high-risk patients [1 –6]. Allogenic blood transfusions represent one of the risk factors that has proved to increase post-operative morbidity and, in particular, the incidence of infective complications [7,8]. Indeed, allogenic blood transfusions may create conditions leading to immune downregulation, a condition known in the literature as allogenic blood transfusion–associated immunomodulation (TRIM) [9 –12]. Its impact on the post-operative course is not negligible, considering that the peri-operative transfusion rate in large cohorts of patients submitted to colorectal surgery ranges from 25.7% to 54.9% [11,13,14].

Leukocyte-depleted blood transfusions (LDBT) have been introduced in many countries in recent years to reduce the negative effects of blood transfusions [13,15,16]. When the clinical impact of LDBT is analyzed, great attention should be paid to the modality of leukocyte depletion, which can be performed in a pre-storage or bedside-filtration setting. Compared with bedside-filtered blood, pre-storage LDBT are supposed to be associated with lower TRIM [17 –19], but the clinical influence of the leukodepletion modality (pre-storage vs. bedside filtration) on post-operative morbidity in patients undergoing colorectal surgery has never been investigated.

The aim of this analysis was to determine whether different types of leukodepletion have different impacts on post-operative morbidity after colorectal resection in order to discover whether pre-storage or bedside-filtered LDBT represents an independent risk factor for post-operative complications, either infectious or non-infectious.

Patients and Methods

Patients

Between November 2006 and March 2011, all patients requiring elective or urgent colorectal resection at the Department of General Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy, were enrolled consecutively in the present study. Clinical data were collected and analyzed retrospectively. All operations were performed by one of five surgeons experienced in colorectal surgery. Preparation for operation and surgical procedures followed criteria reported previously [20].

Preparation of red blood cell concentratesand leukocyte-depletion modality

During the study, donated whole blood was submitted to fractionation by centrifugation, obtaining plasma, buffy coat, and buffy coat-depleted red blood cell concentrates. Most of the buffy coat-depleted packed cells were submitted to leukocyte depletion using pre-storage filters (MacoPharma, Mouveaux, France) within 2 h after donation, obtaining pre-storage LDBT. The rest of buffy coat-depleted red blood cell concentrates were stored, and leukocyte depletion was performed at the time of transfusion (within 42 d from donation) using bedside filters (Fresenius Kabi, Graz, Austria) to yield bedside-filtered LDBT.

Patients who required peri-operative blood transfusions received pre-storage LDBT or bedside-filtered LDBT randomly, according to availability of red blood cell concentrates compatible with patient's blood type at the blood bank, without any correlation with the patient's characteristics.

Hemodynamically important intraoperative blood loss or a low hemoglobin concentration (threshold usually 8 g/dL in the general population and 10 g/dL in the presence of cardiac co-morbidities) were the main indications for blood transfusion.

According to the type of transfusion, patients were divided into three groups: Those not transfused (NT group), those given pre-storage LDBT (PST group), and those receiving bedside-filtered LDBT (BFT group). Patients receiving more than one unit of blood and at least one unit of bedside-filtered LDBT were included in the BFT group. No patient was given whole blood or buffy coat-depleted blood.

Surveillance methods and definition of post-operative morbidity

Post-operative morbidity was defined as complications that contributed to prolonged hospital stay or led to additional procedures. Morbidity was divided into infective and non-infective. An infective complication was defined as presence of general signs of infection (fever, leukocytosis, increasing concentrations of C-reactive protein [CRP]) associated with organ-specific symptoms, and possible detection of specific microorganisms in cultures indicating blood stream infection, sepsis, urinary tract infection, intestinal infection [including Clostridium difficile infection], venous catheter-related infection, surgical site infection [SSI], or other infection).

The diagnosis of SSI was made according to the definitions of the Guidelines of the U.S. Centers for Disease Control and Prevention [21]. An anastomotic leak was not considered a SSI. Post-operative pneumonia was defined as the presence of non-specific signs of infection (fever, leukocytosis, increasing CRP) in association with radiologic demonstration of pulmonary opacity and exclusion of other sites of infection.

Post-operative non-infectious complications, surgical or medical, were defined as any other complication that contributed to a prolonged hospital stay or led to additional procedures (e.g., anastomotic leakage, post-operative ileus or hemorrhage, pulmonary embolism, symptomatic dysrhythmia, myocardial infarction, pleural effusion). Anastomotic leakage was considered in the presence of peritonitis caused by anastomotic dehiscence, leakage of feculent fluid and gas from abdominal drains, and the presence of intra-abdominal fluid collection or abscess around the anastomosis with demonstration of anastomotic leak by endoscopy or contrast study. Post-operative ileus was defined as delayed recovery of bowel function leading to reinsertion of a nasogastric tube or administration of prokinetic agents. Post-operative hemorrhage was defined as bleeding with a decrease in the hemoglobin concentration (>3 g/dL) after the operation that necessitated blood transfusion or re-intervention to stop hemorrhage. Post-operative death was defined as in-hospital death.

For each complication, a severity grade from 1 to 5 was assigned following the Dindo-Clavien classification [22]. If more than one complication occurred in a single patient, all the data related to all the complications were collected, in order to assign a number and a severity score. If more than one complication occurred, the severity score was expressed as the highest grade of complication of that patient.

Factors in post-operative morbidity

The following data were analyzed as risk factors for postoperative morbidity: Age (evaluated as a categorical variable, ≤70 years or >70 years), gender, medical and surgical history, preoperative steroid use, American Society of Anesthesiologists (ASA) score as a categorical variable (<3, ≥3); pre-operative hemoglobin concentration (<11, ≥11 g/dL); pathologic diagnosis (cancer confirmed at definitive pathologic analysis vs. benign diseases), tumor stage (according to Dukes' classification [23]), and pre-operative hospital stay evaluated as a categorical variable (<2 d, ≥2 d). Regarding intra-operative and post-operative course, the following factors were analyzed: Urgent operation, type of colorectal resection detailed as right colon surgery (RCS), left colon surgery (LCS), and rectal surgery (RS), duration of operation (“prolonged operation” was defined as an operation lasting more than the 75th percentile of the examined procedures), need for post-operative intensive care unit (ICU) admission, peri-operative blood transfusions (pre-storage or bedside-filtered LDBT), and surgical wound class (clean-contaminated vs. contaminated or dirty) [24].

Statistical analysis

Data were summarized as frequencies and proportions, and differences between groups were evaluated by the χ² test or Fisher exact test, as appropriate. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated by multiple logistic regression models fitted by the method of maximum likelihood. Statistical significance was set at p<0.05. All statistical analyses were done with the R software package.

Results

A total of 437 patients were included. The indications for colorectal resection were cancer in 313 patients (71.6%; 310 colorectal adenocarcinoma, two anal canal carcinoma, one neuroendocrine tumour of the cecum); diverticulitis in 55 patients (12.5%); inflammatory bowel disease in 11 patients (2.5%); intestinal infarction in 11 patients (2.5%); and other benign colorectal disease in the remaining 48 patients (10.9%). Patient characteristics and peri-operative results are summarized in Table 1. The overall post-operative morbidity rate was 35.6%; infective complications accounted for 28.1%, whereas non-infective complications occurred in 21% of patients (Table 2).

Table 1.

Patient Characteristics and Peri-Operative Results

	N° or Median (% or Range)
Age	69 (26.8; 93.2)
Female/male	198 (45.3)/239 (54.7)
American Society of Anesthesiologists score	2 (1; 5)
Site of surgery
Right colon	168 (38.4)
Left colon or rectum	269 (61.6)
Hospital stay (days)
Pre-operative	1 (0; 84)
Post-operative	10 (0; 83)
Total	12 (0; 117)
Operative time (percentile)
<75th (≤3.45 h)	321 (73.5)
≥75th (≥3.45 h)	116 (26.5)
Surgical site class
Clean-contaminated	358 (81.9)
Contaminated or dirty	79 (18.1)
Post-operative intensive care unit stay
No	402 (92.0)
Yes	35 (8.0)
Diagnosis
Cancer	313 (71.6)
Other	124 (28.4)
Dukes' stage
AB	235 (74.1)
CD	82 (25.9)
Urgent operation
No	390 (89.7)
Yes	45 (10.3)

Table 2.

Post-Operative Morbidity

	Patients (%)
Total	173 (35.6)
Infectious complications	123 (28.1)
Surgical site infection	72 (16.5)
Pneumonia	37 (8.5)
Urinary tract infection	17 (3.9)
Sepsis not specified	10 (2.3)
Central venous catheter infection	4 (0.9)
Clostridium difficile diarrhea	1 (0.2)
Non-infectious complications	92 (21.0)
Pleural effusion	29 (7.1)
Dysrhythmia	24 (5.5)
Post-operative hemorrhage	16 (3.6)
Anastomotic leakage	13 (3.0)
Neurologic disorders	10 (2.3)
Post-operative ileus	9 (2.0)
Heart infarction	7 (1.6)
Deep venous thrombosis	3 (0.7)
Pulmonary embolism	3 (0.7)

Univariable analysis showed that patient age >70 years (p<0.001), ASA score ≥3 (p<0.001), diagnosis of benign disease versus cancer (p=0.053), prolonged operation (p=0.026), “contaminated or dirty” surgical site class (p=0.003), urgent operation (p<0.001), and post-operative ICU admission (p=0.003) were significantly related to higher rates of post-operative morbidity. Patients receiving peri-operative transfusions (PST or BFT) had higher post-operative morbidity rates than patients in the NT group (55.6% vs. 25.4%). Among patients receiving LDBT, patients of the BFT group had a higher incidence of post-operative morbidity than patients in the PST group, with rates of 65.7% and 50.4%, respectively (p<0.001). Results of univariable analysis are reported in detail in Table 3.

Table 3.

Univariate Analysis of Prognostic Factors in Morbidity

		Post-operative morbidity (%)
	All (%)	No	Yes	p value
Age
≤70	233 (53.3)	159 (68.2)	74 (31.8)	<0.001
>70	204 (46.7)	105 (51.5)	99 (48.5)
Gender
Female	198 (45.3)	121 (61.1)	77 (38.9)	0.786
Male	239 (54.7)	143 (59.8)	96 (40.2)
Preoperative hemoglobin (g/dL)
≥11	288 (65.9)	177 (61.3)	111 (38.7)	0.783
<11	149 (34.1)	95 (63.2)	54 (36.8)
American Society of Anesthesiologists score
<3	284 (65.0)	192 (67.6)	92 (32.4)	<0.001
≥3	153 (35.0)	72 (47.1)	81 (52.9)
Diagnosis
Cancer	313 (71.6)	198 (63.3)	115 (36.7)	0.053
Other	124 (28.4)	66 (53.2)	58 (46.8)
Dukes' stage
AB	235 (74.1)	139 (59.2)	96 (40.8)	0.500
CD	82 (25.9)	45 (54.9)	37 (45.1)
Urgent operation
No	391 (89.7)	250 (64.1)	141 (35.9)	<0.001
Yes	46 (10.3)	15 (31.1)	31 (68.9)
Site of surgery
Right colon	168 (38.4)	108 (64.3)	60 (35.7)	0.191
Left colon/rectum	269 (61.6)	156 (58.0)	113 (42.0)
Operative time, percentile
<75th (<3.45 h)	321 (73.5)	204 (63.6)	117 (36.4)	0.026
≥75th (≥3.45 h)	116 (26.5)	60 (51.7)	56 (48.3)
Surgical site class
Clean-contaminated	358 (81.9)	228 (63.7)	130 (36.3)	0.003
Contaminated or dirty	79 (18.1)	36 (45.6)	43 (54.4)
Post-operative intensive care unit stay
No	402 (92.0)	251 (62.4)	151 (37.6)	0.003
Yes	35 (8.0)	13 (37.1)	22 (62.9)
Transfusion (LDBT)
No	232 (53.1)	173 (74.6)	59 (25.4)
Yes	205 (46.9)	91 (44.4)	114 (55.6)	<0.001
Pre-storage	135 (30.9)	67 (49.6)	68 (50.4)
Bedside-filtered	70 (16.0)	24 (34.3)	46 (65.7)

LDBT=leukocyte-depleted blood transfusion.

Statistically significant differences are indicated in boldface.

The prognostic factors that were statistically significant in univariable analysis were evaluated in a multi-variable model. In the present study, the risk of developing post-operative morbidity was 3.33 times higher in transfused than in non-transfused patients (CI 95% 2.14–5.20; p<0.001, corrected for operative time, diagnosis of cancer versus other disease, ASA score, and urgent operation).

When different types of transfusion modalities were analyzed individually, the multi-variable model showed that both BFT and PST were independent risk factors for post-operative complications with an OR of 4.69 in the BFT group and 2.82 in the PST group. Other independent risk factors for post-operative morbidity were prolonged operation, benign disease, ASA score ≥3, and urgent operation (Table 4).

Table 4.

Multi-Variable Analysis of Prognostic Factors on Morbidity

	Odds ratio (95% CI)	p value
Pre-storage: LDBT vs. NT	2.82 (1.73–4.59)	<0.001
Bedside filtered: LDBT vs. NT	4.69 (2.54–8.67)	<0.001
Operative time: ≥75th vs. <75th percentile	1.65 (1.04–2.63)	0.035
Diagnosis: Cancer vs. other	0.56 (0.34–0.92)	0.022
ASA score: ≥3 vs. <3	1.68 (1.07–2.63)	0.023
Urgent operation: Yes vs. no	2.38 (1.15–4.95)	0.020

ASA=American Society of Anesthesiologists; CI=confidence interval; LDBT leukocyte-depleted blood transfusion; NT=not transfused.

Specific infective and non-infective post-operative morbidities of each group of patients (NT, PST, and BFT) were analyzed (Table 5). A comparison between the PST and BFT groups revealed that patients transfused with bedside-filtered LDBT showed significantly higher rates of infective complications (51.4% vs. 31.8%; p=0.006) but similar rates of non-infective complications (35.7% vs. 32.6; p=0.654) than patients given pre-storage LDBT.

Table 5.

Univariable Analysis of Effect of Transfusions on Post-Operative Morbidity

		Transfusion
	All (%)	NT (%)	PST (%)	BFT (%)	p value ^a
Post-operative morbidity
No	264 (60.4)	173 (74.6)	67 (49.6)	24 (34.3)	<0.001
Yes	173 (35.6)	59 (25.4)	68 (50.4)	46 (65.7)	0.036
Infectious complications
No	315 (71.9)	188 (81.0)	92 (68.2)	34 (48.6)	<0.001
Yes	123 (28.1)	44 (19.0)	43 (31.8)	36 (51.4)	0.006
No. of infectious complications in same patient
0	315 (71.9)	188 (81.0)	92 (68.2)	34 (48.6)	<0.001
1	106 (24.2)	41 (17.7)	35 (25.9)	30 (42.9)
2	16 (3.7)	3 (1.3)	8 (5.9)	5 (7.1)	0.028
3	1 (0.2)	0 (0.0)	0 (0.0)	1 (1.4)
Grade of infectious complications
0	315 (71.9)	188 (81.0)	92 (68.2)	34 (48.6)
1	45 (10.3)	20 (8.6)	14 (10.4)	11 (15.7)	<0.001
2	62 (14.2)	22 (9.5)	21 (15.6)	19 (27.1)
3	9 (2.0)	1 (0.4)	5 (3.7)	3 (4.3)	0.048
4	3 (0.7)	1 (0.4)	2 (1.5)	0 (0.0)
5	4 (0.9)	0 (0.0)	1 (0.7)	3 (4.3)
Non-infectious complications
No	346 (79.0)	209 (90.1)	91 (67.4)	45 (64.3)	<0.001
Yes	92 (21.0)	23 (9.9)	44 (32.6)	25 (35.7)	0.654
No. of non-infectious complications in same patient
0	346 (79.0)	209 (90.1)	91 (67.4)	45 (64.3)	<0.001
1	73 (16.7)	20 (8.6)	33 (24.4)	20 (28.6)
2	16 (3.7)	3 (1.3)	8 (5.9)	5 (7.1)	0.565
3	3 (0.7)	0 (0.0)	3 (2.2)	0 (0.0)
Grade of non-infectious complications
0	346 (79.0)	209 (90.1)	91 (67.4)	45 (64.3)
1	31 (7.1)	11 (4.7)	15 (11.1)	5 (7.1)	<0.001
2	38 (8.7)	6 (2.6)	20 (14.8)	12 (17.1)
3	10 (2.3)	4 (1.7)	3 (2.2)	3 (4.3)
4	8 (1.8)	2 (0.9)	3 (2.2)	3 (4.3)	0.793
5	5 (1.1)	0 (0.0)	3 (2.2)	2 (2.9)

P value in open cells refers to all three groups; p value in shaded cells refers to comparison of PST and BST. Statistically significant differences indicated in boldface.

NT=non-transfused; PST=pre-storage transfused; BFT=bedside-filtered transfusion.

Discussion

In the present study on multi-variable analysis several parameters proved to be independent factors for increasing postoperative morbidity: ASA score ≥3, prolonged operation, benign disease versus cancer, urgent setting, and both PST and BFT. Among these risk factors, ASA score≥3, prolonged operation, and urgent operation are well-known risk factors for post-operative morbidity and death after colorectal resection [5,14,25,26]. Given that cancer patients are supposed to have impaired immune competence [27], it could be surprising that patients with cancer showed a significantly lower incidence of post-operative complications than patients without cancer (36.7% vs. 46.8%, respectively; OR 0.56; p=0.022). These results can be explained easily, in that patients without cancer were operated on more frequently in an urgent setting and in contaminated/dirty conditions, both predictors of post-operative morbidity in this analysis.

Although only LDBT were administered in this study, blood transfusion was an independent risk factor for post-operative morbidity, with the risk of complications being 3.33-fold higher in transfused patients (p<0.001). It may be argued that transfused patients had poorer outcomes because of anemia and not because of transfusion per se, but as low pre-operative hemoglobin concentrations had no significant influence on morbidity (p=0.783), this explanation seems unlikely.

There have been six randomized controlled trials (RCTs) evaluating morbidity after colorectal surgery in patients transfused with LDBT versus buffy coat-depleted transfusions. Four of the studies demonstrated significantly reduced morbidity in patients receiving LDBT [10,13,28,29]; two of them showed similar morbidity in the groups, but both found a trend toward a lower rate of complications after LDBT [16,30]. It is remarkable that in both RCT and non-randomized trials the leukodepletion modality was mostly the bedside-filtered type or not specified. Similarly, several studies demonstrated that in open heart surgery, leukoreduction curtailed postoperative multiple organ dysfunction syndrome, infections, and the short-term mortality rate [31,32].

In the present analysis, the authors investigated whether the type of leukocyte-depletion modality affected post-operative morbidity. Indeed, the multi-variable model evidenced that bedside-filtered and pre-storage-filtered LDBT had ORs for complications of 4.69 and 2.82, respectively, compared with non-transfusion. Consequently, administration of BFTs is associated with significantly greater post-operative morbidity; indeed, it was the most powerful risk factor for post-operative morbidity in the patients enrolled in the present study.

Previous in vitro studies proved that white blood cell (WBC) reduction by bedside filtration appears inadequate compared with pre-storage filtration [33,34]. Furthermore, as it is performed shortly after blood donation, pre-storage depletion has proved to be effective in removing leukocytes before cytokine production and release of bioactive substances (histamine, 2-eosinophil cationic protein, eosinophil protein X, myeloperoxidase, and plasminogen activator inhibitor-12) contained in intracellular WBC granules. By contrast, bedside leukocyte filtration is performed just before the transfusion and can occur even several days after the donation, therefore after production and release of cytokines and bioactive substances normally contained in WBCs and related to TRIM [17 –19].

In the present study, NT, PST, and BFT resulted in different outcomes for total, infectious, and non-infectious morbidity. In detail, when a direct comparison of the PST and BFT groups was performed, the difference between the two groups appeared remarkable for the infectious complication rate (31.8% vs. 51.4%, respectively; p=0.006), whereas the non-infectious complication rates were similar (32.6% vs. 35.7%; p=0.654). Consequently, the statistical significance in the non-infective complications in the NT, PST, and BFT groups should be attributed mostly to the difference between transfused and non-transfused patients. Moreover, analyzing the number and the grade of infectious complications, patients of the BFT group had a higher number (p=0.028) and greater severity (p=0.048) of infectious complications than patients in the BFT group; for non-infectious morbidity, this trend was not confirmed (Table 5).

These outcomes are consistent with the rationale of the study, because the strongest TRIM related to bedside filtration should affect the infectious more than the non-infectious complications, because non-infectious morbidity appears related more to the surgical intervention than to the host's immune function. A meta-analysis demonstrated an association between BFT and post-operative infection; this result was not confirmed for PST [32]. In trauma patients, several retrospective studies demonsted that the use of pre-storage leukoreduction is associated with a reduction in infectious complications [35,36].

To the authors' knowledge, this is the first study with direct comparison of the incidence of post-operative complications in patients undergoing colorectal surgery who received transfusions of pre-storage or bedside-filtered LDBT.

The only RCT investigating the effect of different types of leukoreduction in surgical patients dealt with open heart surgery; it showed that infectious complication rates did not differ in patients transfused with pre-storage or post-storage LDBT [31]. These results appear in contrast with the ones obtained in the present study. Nevertheless, cardiac and colorectal surgery differ in several risk factors for infectious complications, and in particular for SSI, which represents the most common infectious complication of colorectal surgery. For instance, the bacterial contamination class usually is “clean” in heart surgery, whereas in colorectal surgery, it ranges from “clean-contaminated” to “dirty.” Moreover, the contaminating bacterial flora is different in the two types of surgery.

Because the results of this survey showed that the leukodepletion modality is of paramount importance for the outcome of patients undergoing colorectal resection, great attention should be paid to which type of transfusion is administered in this setting. Even if pre-storage leukodepletion is expensive, its use should be expanded in order to reduce post-operative morbidity and costs related to prolonged hospital stays and post-operative interventional procedures.

Both surgeons and anesthesiologists should be more careful and restrictive with the use of peri-operative blood transfusions because it is clear that post-operative morbidity is strongly affected by any type of transfusion, pre-storage LDBT included. Clinical and surgical tactics should be developed to reduce the need for blood transfusion, as this might improve surgical outcomes. This fact is important during colorectal resection, because the wall of the colon is breached, and bacterial contamination of the surgical field can represent a direct potential source of infectious complications. If an allogenic transfusion obviously is indicated, pre-storage LDBT should be preferred. It is remarkable that these data should be confirmed in a randomized trial, and the impact of the leukodepletion modality on long-term survival and on tumor recurrence should be evaluated in specific populations with colorectal cancer.

Conclusions

The present study demonstrated that both pre-storage and bedside-filtered LDBT are independent risk factors for postoperative complications after colorectal resection. Bedside-filtered LDBT showed a significantly more negative impact on post-operative morbidity than pre-storage LDBT; consequently, the leukodepletion modality is an important prognostic factor for post-operative infective morbidity, and if a transfusion is strictly indicated, pre-storage LDBT should be preferred.

Footnotes

Author Disclosure Statement

The authors declare no conflicts of interest. No funding was received for this study.

References

Koch

, Antolovic

, Reissfelder

et al. Leucocyte-depleted blood transfusion is an independent predictor of surgical morbidity in patients undergoing elective colon cancer surgery: A single-center analysis of 531 patients. Ann Surg Oncol, 2011; 18:1404–1411.

Bokey

, Chapuis

, Fung

et al. Postoperative morbidity and mortality following resection of the colon and rectum for cancer. Dis Colon Rectum, 1995; 38:480–486.

Longo

, Virgo

, Johnson

et al. Risk factors for morbidity and mortality after colectomy for colon cancer. Dis Colon Rectum, 2000; 43:83–91.

Stillwell

, Buettner

, Siu

et al. Predictors of postoperative mortality, morbidity, and long-term survival after palliative resection in patients with colorectal cancer. Dis Colon Rectum, 2011; 54:535–544.

Staib

, Link

, Blatz

, Beger

. Surgery of colorectal cancer: Surgical morbidity and five- and ten-year results in 2400 patients: Monoinstitutional experience. World J Surg, 2002; 26:59–66.

Richards

, Platt

, Anderson

et al. The impact of perioperative risk, tumor pathology and surgical complications on disease recurrence following potentially curative resection of colorectal cancer. Ann Surg, 2011; 254:83–89.

Amato

, Pescatori

. Perioperative blood transfusions for the recurrence of colorectal cancer. Cochrane Database Syst Rev, 2006; CD005033.

Duffy

, Neal

. Differences in post-operative infection rates between patients receiving autologous and allogeneic blood transfusion: A meta-analysis of published randomized and nonrandomized studies. Transfus Med, 1996; 6:325–328.

Heiss

, Mempel

, Jausch

. Beneficial effect of autologous blood transfusion on infectious complications after colorectal cancer surgery. Lancet, 1993; 342:1328–1333.

10.

Jensen

, Andersen

, Christiansen

. Postoperative infection and natural killer cell function following blood transfusion in patients undergoing elective colorectal surgery. Br J Surg, 1992; 79:513–516.

11.

Busch

, Hop

, Hoynck van Papendrecht

et al. Blood transfusions and prognosis in colorectal cancer. N Engl J Med, 1993; 328:1372–1376.

12.

Vamvakas

, Blajchman

. Deleterious clinical effects of transfusion-associated immunomodulation: Fact or fiction? Blood, 2001; 97:1180–1195.

13.

Jensen

, Kissmeyer-Nielsen

, Wolff

, Qvist

. Randomised comparison of leucocyte-depleted versus buffy-coat-poor blood transfusion and complications after colorectal surgery. Lancet, 1996; 348:841–845.

14.

Ferjani

, Griffin

, Stallard

, Wong

. A newly devised scoring system for prediction of mortality in patients with colorectal cancer: A prospective study. Lancet Oncol, 2007; 8:317–322.

15.

Williamson

, Murphy

, Llewelyn

et al. Leucocyte-depleted blood in prevention of post-operative infections following elective orthopaedic and cardiac procedures. Vox Sang, 2002; 83,Suppl 1:457–460.

16.

Titlestad

, Ebbesen

, Ainsworth

et al. Leukocyte-depletion of blood components does not significantly reduce the risk of infectious complications: Results of a double-blinded, randomized study. Int J Colorectal Dis, 2001; 16:147–153.

17.

Nielsen

, Edvardsen

, Vangsgaard

et al. Time-dependent histamine release from stored human blood products. Br J Surg, 1996; 83:259–262.

18.

Nielsen

, Reimert

, Pedersen

et al. Time-dependent, spontaneous release of white cell- and platelet-derived bioactive substances from stored human blood. Transfusion, 1996; 36:960–965.

19.

Vamvakas

, Blajchman

. Prestorage versus poststorage white cell reduction for the prevention of the deleterious immunomodulatory effects of allogeneic blood transfusion. Transfus Med Rev, 2000; 14:23–33.

20.

Degrate

, Garancini

, Misani

et al. Right colon, left colon, and rectal surgeries are not similar for surgical site infection development: Analysis of 277 elective and urgent colorectal resections. Int J Colorectal Dis, 2011; 26:61–69.

21.

Mangram

, Horan

, Pearson

et al. Guideline for prevention of surgical site infection 1999. Hospital Infection Control Practices Advisory Committee. Infect Control Hosp Epidemiol, 1999; 20:250–278.

22.

Dindo

, Demartines

, Clavien

. Classification of surgical complications: A new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg, 2004; 240:205–213.

23.

Dukes

. The classification of cancer of the rectum. J Pathol Bacteriol, 1932; 35:323.

24.

Culver

, Horan

, Gaynes

et al. Surgical wound infection rates by wound class, operative procedure, and patient risk index. National Nosocomial Infections Surveillance System. Am J Med, 1991; 91:152S–157S.

25.

Fazio

, Tekkis

, Remzi

, Lavery

. Assessment of operative risk in colorectal cancer surgery: The Cleveland Clinic Foundation colorectal cancer model. Dis Colon Rectum, 2004; 47:2015–2024.

26.

Hendry

, Hausel

, Nygren

et al. Enhanced recovery after surgery study group: Determinants of outcome after colorectal resection within an enhanced recovery programme. Br J Surg, 2009; 96:197–205.

27.

Dillman

, Koziol

, Zavanelli

et al. Immunoincompetence in cancer patients: Assessment by in vitro stimulation tests and quantification of lymphocyte subpopulations. Cancer, 1984; 53:1484–1491.

28.

Skånberg

, Lundholm

, Haglind

. Effects of blood transfusion with leucocyte depletion on length of hospital stay, respiratory assistance and survival after curative surgery for colorectal cancer. Acta Oncol, 2007; 46:1123–1130.

29.

Tartter

, Mohandas

, Azar

et al. Randomized trial comparing packed red cell blood transfusion with and without leukocyte depletion for gastrointestinal surgery. Am J Surg, 1998; 176:462–466.

30.

Houbiers

, Brand

, van de Watering

et al. Randomised controlled trial comparing transfusion of leucocyte-depleted or buffy-coat-depleted blood in surgery for colorectal cancer. Lancet, 1994; 27,344:573–578.

31.

van de Watering

LMG

, Hermans

, Houbiers

JGA

et al. Beneficial effect of leukocyte depletion of transfused blood on post-operative complications in patients undergoing cardiac surgery: A randomized clinical trial. Circulation, 1998; 97:562–568.

32.

Vamvakas

. White-blood-containig allogenic blood transfusion and postoperative infection or mortality: An updated meta-analysis. Vox Sang, 2007; 92:224–232.

33.

Ledent

, Berlin

. Inadequate white cell reduction by bedside filtration of red cell concentrates. Transfusion, 1994; 34:765–768.

34.

Sprogoe-Jakobsen

, Saetre

, Georgsen

. Preparation of white cell-reduced red cells by filtration: Comparison of a bedside filter and two blood bank filter systems. Transfusion, 1995; 35:421–426.

35.

Phelan

, Gonzalez

, Patel

et al. Prestorage leukoreduction ameliorates the effect of aging on banked blood. J Trauma, 2010; 69:330–337.

36.

Friese

, Sperry

, Phelan

, Gentilello

. The use of leukoreduced red blood cell products is associated with fewer infectious complications in trauma patients. Am J Surg, 2008; 196:56–61.