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Keywords:

  • blood transfusion;
  • nephrectomy;
  • renal cell carcinoma

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Conflict of Interest
  8. References

What's known on the subject? and What does the study add?

  • There is a paucity of population-based analyses of expected outcomes after renal surgery for kidney cancer. Reported blood transfusion rates after nephrectomy show considerable variability, probably as a result of the referral patterns that influence reports from tertiary academic medical centres.
  • With emerging data on the inferior outcomes in patients undergoing allogeneic blood transfusion, we aimed to evaluate the patient, surgeon and hospital factors that influence the receipt of a blood transfusion after nephrectomy. A more detailed understanding of these factors may help in preoperative patient counselling and informed consent.

Objective

  • To examine blood transfusion rates after nephrectomy for renal masses at the population-level.

Patients and Methods

  • We performed a population-based, retrospective observational study using a national discharge abstract database.
  • The study cohort consisted of 10 902 patients who were treated by radical nephrectomy (RN) or partial nephrectomy (PN) for a renal mass between 1 April 2003 and 31 March 2008.
  • The association between blood transfusion and various explanatory variables was examined using the chi-squared test and multivariable logistic regression.

Results

  • The overall blood transfusion rate was 18.1%.
  • Transfusions occurred after 28.2%, 12.7%, 9.2% and 8.6% of open RN, open PN, laparoscopic RN and laparoscopic PN, respectively (P < 0.001).
  • Transfusion rates were found to be strongly associated with age and comorbidity, such that patients aged <50 years with Charlson scores of 0 were transfused 11.2% and 14.5% of the time compared to 28.2% and 40.7% in patients aged ≥80 years with Charlson scores of ≥3, respectively (P < 0.001).
  • On multivariable logistic regression, age (P < 0.001), Charlson score (P < 0.001), procedure type (P < 0.001), surgeon (P < 0.001) and hospital volume quartile (P < 0.001) were all found to be associated with the rate of blood transfusions, whereas year of surgery, sex and income quintile were not.

Conclusions

  • The transfusion rate after nephrectomy in general clinical practice is higher than that reported in the urological literature.
  • Patient and provider factors appear to contribute to the considerable variability that exists in the observed transfusion rate.
  • A more detailed understanding of these factors may help with respect to preoperative patient counselling and informed consent.

Abbreviations
CDI

Charlson Index

CIHI

Canadian Institute for Health Information

DAD

Discharge Abstract Database

FSA

forward sortation area

LPN

laparoscopic partial nephrectomy

LRN

laparoscopic radical nephrectomy

OPN

open partial nephrectomy

ORN

open radical nephrectomy

PBT

peri-operative blood transfusion

PN

partial nephrectomy

pRBC

packed red blood cell

RN

radical nephrectomy

Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Conflict of Interest
  8. References

Each year, almost 75 million units of blood are collected worldwide, with peri-operative blood transfusion (PBT) accounting for ≈15 million units of packed red blood cells (pRBCs) transfused annually in the USA alone [1]. Currently, the indications triggering a PBT remain poorly defined and, although the safety of pRBC transfusion has improved dramatically, major risks remain [2].

Reported blood transfusion rates after nephrectomy show considerable variability, probably as a result of the referral patterns that influence reports from tertiary academic centres. With most of the outcomes data in urological oncology originating from higher volume surgeons and institutions, the paucity of population-based analyses makes current understanding of expected outcomes after renal surgery for kidney cancer susceptible to publication and reporting bias. Only recently has there been a population-based study looking at postoperative complications, blood transfusion rate and length of stay after nephrectomy for renal masses [3]. This dearth of published results is especially true when critically evaluating the outcomes of highly technical procedures, such as laparoscopic partial nephrectomy (LPN) [4].

Given these factors, coupled with the emerging data on the inferior outcomes in patients undergoing allogeneic blood transfusion, the present study aimed to evaluate the patient, surgeon and hospital factors that may influence receiving a PBT after nephrectomy for renal tumours. A more detailed understanding of these factors may help with respect to preoperative patient counselling and informed consent.

Patients and Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Conflict of Interest
  8. References

Source Data and Study Sample

This was a population-based, retrospective, observational study using administrative data. Data were obtained from the Canadian Institute for Health Information (CIHI) Discharge Abstract Database (DAD). The latter is a national database of all admissions to acute care institutions, and includes all Canadian provinces except Quebec [5]. Laparoscopic procedure codes were only available as of 2003; accordingly, the present study included all acute inpatient records on patients treated by either laparoscopic radical nephrectomy (LRN) or open radical nephrectomy (ORN) or open partial nephrectomy (OPN) from 1 April 2003 to 31 March 31 2008.

The initial study sample included information totalling 35 039 discharge abstracts from April 1998 to 31 March 2008. We restricted the sample to patients aged ≥18 years (which excluded 534 abstracts). We excluded 9926 patients who underwent nephrectomy for an indication other than a renal mass (e.g. urothelial carcinoma, infection, polycystic kidney disease, non-function, etc.). We also excluded data before 2003 because codes on operative approach (i.e. open vs laparoscopic) were not available during that time (which excluded 11 003 abstracts). Finally, we excluded data from two provinces (Manitoba and British Columbia) where the reporting of blood transfusions was not mandatory (which excluded 2674 abstracts), leaving a final study sample of 10 902 discharge abstracts.

Variables

Demographic variables available from the CIHI DAD and analyzed in the study included age, sex and forward sortation area (FSA; the first three digits of the postal code). Age was analyzed as both a continuous and a five-level categorical variable (<50, 50–59, 60–69, 70–79, ≥80). FSA was used as an ecological proxy to estimate income quintile. Median individual income estimates were obtained for each FSA using Canadian 2006 census data and grouped into quintiles [6]. Additionally, given that the numbers of patients varied considerably between provinces, provinces were grouped into regions to allow adequate numbers for comparison. Provincial groupings were created for Atlantic (New Brunswick, Nova Scotia, Newfoundland and Prince Edward Island) and Prairie provinces (Alberta and Saskatchewan), whereas Ontario was analyzed independently. Using the total number of kidney procedures performed during the 5-year observation period, surgeon and hospital volume quartiles were also created for analysis.

CIHI permits a maximum of 25 diagnostic codes per hospitalization file in the DAD (comorbid conditions and complications). In the present study, adjustment of comorbidity was performed using the Deyo adaptation of the Charlson Index (CDI), one of the most commonly used comorbidity measures for administrative data [7, 8]. Furthermore, as is standard for the CDI, patients were not scored for their primary diagnosis, which in this case was kidney cancer [9]. Procedure types were coded as ORN, OPN, LRN and LPN.

There were no missing data for fiscal year, age, sex or CDI category. Provincial region and income quintile were not available in two (8.2 × 10–5%) and 285 (1.2%) patients from the original dataset, respectively.

Statistical Analysis

Blood transfusion rates were estimated by procedure type, as well as by various explanatory variables (i.e. age, Charlson score, fiscal year, sex and provincial region), and compared using the chi-squared test. To adjust for multiple covariates, a multivariable logistic regression analysis was performed to determine the association between variables of interest and the probability of receiving a blood transfusion after surgery. P < 0.05 was considered statistically significant. All analyses were performed using SAS, version 9.2 (SAS Institute Inc., Cary, NC, USA).

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Conflict of Interest
  8. References

Descriptive statistics are provided for the entire patient cohort (Table 1). The absolute number of cases performed annually did not differ appreciably throughout the 5-year observation period. The median patient age was 62 years, with most patients being aged between 50 and 79 years. Over three-quarters of the patient sample lacked significant medical comorbidities (i.e. a Charlson score of 0), with three-fifths of the cohort being men. Most patients (77.8%) underwent RN (8484 patients), with the greater part of these being treated with ORN. Only 5.5% (602 patients) of the cohort underwent LPN.

Table 1. Descriptive statistics for the cohort.
VariableFrequencyDid not receive PBTReceived PBT
  1. LPN, laparoscopic partial nephrectomy; LRN, laparoscopic radical nephrectomy; OPN, open partial nephrectomy; ORN, open radical nephrectomy; PBT, peri-operative blood transfusion; PN, partial nephrectomy; RN, radical nephrectomy.

Number of patients10 9028934 (82)1968 (18)
Age (years), mean (median, range)61 (62, 18–95)
Sex, n (% total)   
Female4 309 (39.5)3543 (82.2)766 (17.8)
Male6 593 (60.5)5391 (81.8)1202 (18.2)
Procedure type, n (% total)   
RN8 484 (77.8)6799 (80)1685 (20)
PN2 418 (22.2)2135 (88.3)283 (11.7)
ORN4 762 (43.7)3420 (71.8)1342 (28.2)
LRN3 722 (34.1)3379 (90.8)343 (9.2)
OPN1 816 (16.7)1585 (87.3)231 (12.7)
LPN602 (5.5)550 (91.4)52 (8.6)
Age category (years), n (% total)   
<502 017 (18.5)1792 (88.8)225 (11.2)
50–592 728 (25)2326 (85.3)402 (14.7)
60–693 003 (27.6)2456 (81.8)547 (18.2)
70–802 449 (22.5)1854 (75.7)595 (24.3)
>80705 (6.5)506 (71.8)199 (28.2)
Region, n (% total)   
Atlantic1 913 (17.6)1564 (81.8)349 (18.2)
Ontario6 840 (62.7)5579 (81.6)1261 (18.4)
Prairie2 149 (19.7)1791 (83.3)358 (16.7)
Year of surgery, number of procedures (% total)   
20031 900 (17.4)1549 (81.5)351 (18.5)
20042 041 (18.7)1657 (81.2)384 (18.8)
20052 155 (19.8)1760 (81.7)395 (18.3)
20062 333 (21.4)1933 (82.9)400 (17.1)
20072 473 (22.7)2035 (82.3)438 (17.7)
Charlson comorbidity index score, n (% total)   
08 389 (77)7174 (85.5)1215 (14.5)
11 484 (13.6)1117 (75.3)367 (24.7)
2705 (6.4)451 (64)254 (36)
3324 (3)192 (59.3)132 (40.7)
Surgeon volume in quartiles, n (% total)   
1st1 731 (15.9)1273 (73.5)458 (26.5)
2nd2 050 (18.8)1688 (82.3)362 (17.7)
3rd3 335 (30.6)2828 (84.8)507 (15.2)
4th3 786 (34.7)3145 (83.1)641 (16.9)
Hospital volume in quartiles, n (% total)   
1st2 101 (19.3)1633 (77.7)468 (22.3)
2nd2 813 (25.8)2380 (84.6)433 (15.4)
3rd2 518 (23.1)2051 (81.5)467 (18.5)
4th3 470 (31.8)2870 (82.7)600 (17.3)
Patient income in quintiles, n (% total)   
1st2 168 (20.1)1749 (80.7)419 (19.3)
2nd1 948 (18)1583 (81.3)365 (18.7)
3rd2 044 (18.9)1688 (82.6)356 (17.4)
4th2 230 (20.7)1845 (82.7)385 (17.3)
5th2 410 (22.3)1986 (82.4)424 (17.6)

Overall, 1968 (18%) patients received a PBT. Patients undergoing RN had a greater probability of requiring a blood transfusion than those who underwent PN: 19.9% vs 11.7%, respectively (P < 0.001). Over one-quarter (28.2%) of patients undergoing ORN received a PBT. This transfusion rate decreased steadily, such that 12.7%, 9.2% and 8.6% of patients undergoing OPN, LRN and LPN received a PBT, respectively. The rate of PBT was found to be most strongly associated with patient age and CDI score, such that patients aged <50 years old and with Charlson scores of 0 were transfused 11.2% and 14.5% of the time compared to 28.2% and 40.7% in patients aged ≥80 years and with Charlson scores of ≥3 or more (P < 0.001).

A number of associations were found between the receipt of a PBT and various explanatory variables after open and laparoscopic surgery for kidney cancer. The variables examined were procedure type, sex, age, region, surgeon and hospital volume, socioeconomic status, year of surgery and CDI score (Table 2). Multivariable logistic regression showed procedure type, patient age, Charlson score, hospital and surgeon volume to be strongly associated with the probability of receiving a blood transfusion.

Table 2. Univariate and multivariate analyses of the probability of receiving a peri-operative blood transfusion stratified by patient and provider variables.
VariableTransfusion rate, n (% total)

Univariable analysis

OR (95% CI)

Overall

P value

Multivariable analysis

OR (95% CI)

Overall

P value

  1. LPN, laparoscopic partial nephrectomy; LRN, laparoscopic radical nephrectomy; OPN, open partial nephrectomy; OR, odds ratio; ORN, open radical nephrectomy; PN, partial nephrectomy; RN, radical nephrectomy.

Procedure type  <0.001 <0.001
RN1685 (19.9)ReferentReferent
PN283 (11.7)OR 0.6 (0.52–0.69)OR 0.54 (0.47–0.61)
ORN1342 (28.2)ReferentReferent
LRN343 (9.2)OR 0.26 (0.23–0.29)OR 0.25 (0.22–0.29)
OPN231 (12.7)OR 0.37 (0.32–0.43)OR 0.38 (0.32–0.45)
LPN52 (8.6)OR 0.24 (0.18–0.32)OR 0.24 (0.18–0.33)
Age category (years)  <0.001 <0.001
<50225 (11.2)ReferentReferent
50–59402 (14.7)OR 1.4 (1.2–1.6)OR 1.26 (1.05–1.5)
60–69547 (18.2)OR 1.8 (1.5–2.1)OR 1.5 (1.26–1.8)
70–80595 (24.3)OR 2.6 (2.2–3)OR 2.1 (1.7–2.5)
>80199 (28.2)OR 3.1 (2.5–3.9)OR 2.5 (1.97–3.12)
Sex OR 1 (0.91–1.1)0.93OR 1.01 (0.91–1.13)0.8
Male1202 (18.2)
Female766 (17.8)
Region  0.002 <0.001
Atlantic349 (18.2)OR 0.94 (0.79–1.1)OR 0.81 (0.68–0.96)
Ontario1261 (18.4)ReferentReferent
Prairie358 (16.7)OR 0.77 (0.67–0.89)OR 0.69 (0.6–0.8)
Surgeon volume in quartiles  <0.001 <0.001
1st458 (26.5)ReferentReferent
2nd362 (17.7)OR 0.6 (0.5–0.7)OR 0.7 (0.6–0.84)
3rd507 (15.2)OR 0.5 (0.4–0.6)OR 0.7 (0.6–0.82)
4th641 (16.9)OR 0.6 (0.5–0.65)OR 0.8 (0.69–0.94)
Hospital volume in quartiles  <0.001 <0.001
1st468 (22.3)ReferentReferent
2nd433 (15.4)OR 0.6 (0.55–0.7)OR 0.79 (0.67–0.93)
3rd467 (18.6)OR 0.8 (0.69–0.9)OR 1.36 (1.14–1.6)
4th600 (17.3)OR 0.7 (0.6–0.84)OR 1.17 (0.99–1.38)
Charlson score  <0.001 <0.001
01215 (14.5)ReferentReferent
1367 (24.7)OR 1.9 (1.7–2.2)OR 1.77 (1.5–2.04)
2254 (36)OR 3.3 (2.8–3.9)OR 2.82 (2.4–3.36)
3132 (40.7)OR 4 (3.2–5.1)OR 3.5 (2.7–4.47)
Patient income in quintiles  0.71 0.61
1st419 (19.3)ReferentReferent
2nd365 (18.7)OR 0.96 (0.8–1.1)OR 0.88 (0.74–1.05)
3rd356 (17.4)OR 0.88 (0.75–1.02)OR 0.95 (0.79–1.13)
4th385 (17.3)OR 0.87 (0.75–1.02)OR 0.89 (0.74–1.06)
5th424 (17.6)OR 0.89 (0.77–1.04)OR 0.92 (0.77–1.1)
Year of surgery  0.30 0.57
2003351 (18.5)ReferentReferent
2004384 (18.8)OR 1.02 (0.87–1.2)OR 1.08 (0.91–1.29)
2005395 (18.3)OR 0.99 (0.85–1.16)OR 1.1 (0.93–1.3)
2006400 (17.1)OR 0.91 (0.78–1.1)OR 1.03 (0.87–1.23)
2007438 (17.7)OR 0.95 (0.8–1.1)OR 1.14 (0.96–1.34)

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Conflict of Interest
  8. References

Although it is almost 200 years since the first successful human blood transfusions took place [10], contemporary knowledge regarding the indications and complications of allogeneic blood transfusion remains poorly defined. Even less certain is the critical threshold at which blood transfusion should be performed in the peri-operative period. Although the increase in oxygen transport capacity afforded by the transfusion of pRBCs can be critical in situations of life-threatening anaemia, their benefit in terms of decreased morbidity and mortality remains largely unproven. Several large clinical trials have shown significant detrimental effects stemming from the use of a liberal vs a more restrictive transfusion strategy in critically ill patients.

In the largest and perhaps most widely cited clinical trial evaluating pRBC transfusion thresholds, the Transfusion Requirement in Critical Care investigators prospectively randomized over 800 critically ill adults with haemoglobin values <9 g/dL to one of two transfusion groups [11]. The ‘restrictive’ group received pRBC transfusions only when the haemoglobin concentration fell <7 g/dL, whereas the ‘liberal’ group was transfused to maintain a haemoglobin level >10 g/dL. The primary outcome variable of 30-day mortality did not differ between these two groups (18.7% in restrictive group vs 23.3% in liberal group, P = 0.10). Additionally, there was a significant increase in cardiac and pulmonary complications noted among patients in the liberal transfusion group. Moreover, among patients who were objectively less critically ill and/or aged <55 years, a restrictive transfusion policy showed a significant reduction in 30-day mortality. There are two other large, prospective observational studies in critically ill patients [12, 13] reporting similar results.

The overall pRBC transfusion rate for patients in the present study was 18.1%, with over one-quarter (28.2%) of patients undergoing ORN requiring at least one unit of pRBCs after surgery. The transfusion rate decreased steadily, with 12.7%, 9.2% and 8.6% of patients requiring pRBC transfusion after OPN, LRN and LPN, respectively. It is not surprising that patients in this series undergoing ORN had a higher rate of PBT considering the current indications for ORN would be tumours not deemed to be amenable to laparoscopic resection, which are in theory more complex and have the potential for higher blood loss. What is somewhat unexpected is the actual transfusion rate of 28.2% for those patients undergoing ORN because this is well above the rates reported in the urological literature [14, 15]. A recent study by Jeong et al. [14] compared LRN and ORN for clinical stage T2 or less RCC. The reported rates of blood transfusion for ORN and LRN were 4.3% and 3.6%, respectively. It should be noted, however, that 88% of these tumours were pT1a or pT1b, which may have contributed to the lower rate of blood transfusion compared to that of the present study. In another recent study, Tan et al. [15] used linked Surveillance, Epidemiology and End Results–Medicare data to compare the effectiveness of laparoscopic vs ORN for patients with RCC. The overall rate of blood transfusion between ORN and LRN was 4.2% and 1.9%, respectively, again significantly lower than the rates reported for the cohort in the present study.

When comparing the transfusion rates after OPN vs LPN, we found an absolute lower rate of PBT after LPN of 4.1%, which reached statistical significance (P < 0.001). The rate of PBT after LPN in the cohort in the present study (8.6%) was on a par with the largest reported case series of LPN, with 12.5% of these patients requiring blood transfusion [16]. In perhaps one of the largest reported series comparing OPN and LPN, Gill et al. [17] found LPN to be associated with decreased operative blood loss. However, when comparing transfusion rates between these two groups, no significant difference was found, with 4.5% and 5.1% of patients requiring PBT after LPN and OPN, respectively. It should be noted, however, that the group of patients undergoing OPN had a larger percentage of tumours that were >4 cm, centrally located and ultimately found to be malignant. We suggest that this selection bias was a predominant factor for ultimate PBT in the group in the present study as well and may not necessarily be related to the operative approach selected.

The CIHI DAD allowed the surgical outcome of PBT for kidney cancer to be studied on a large scale. Using multivariable logistic regression, age, Charlson score, procedure type, surgeon and hospital volume quartile were found to be strongly associated with the rate of blood transfusions, whereas year of surgery, sex and income quintile were not.

Interest in the regionalization of care has led to numerous studies in the last decade investigating the impact of hospital case volume on surgical outcomes [18]. A number of other studies have examined the relationship between surgeon and hospital volume vs outcomes after surgery for kidney cancer. Consistent with the findings of the present study, these studies have highlighted the positive relationship between high surgeon and/or hospital volume and decreased complication rates, including PBT [19, 20].

An important question in urological oncology is whether PBT has a negative impact on recurrence and survival in patients undergoing extirpative procedures for urological malignancy. A number of studies in both the general surgery and surgical subspecialty literature have addressed this issue with conflicting results [21-25]. The putative mechanism by which PBT is considered to negatively impact oncological outcomes revolves around immunosuppression, referred to as transfusion-associated immunomodulation [26]. The transient immunosuppression afforded by allogeneic blood transfusions may lead to reduced tumour surveillance and thus increase the metastatic potential of the primary tumour [27].

There are only two studies available in the urological literature investigating the association between PBT and cancer recurrence after definitive treatment [28, 29]. Both studies were retrospective reviews for consecutive patients who underwent radical prostatectomy in the USA and Europe. When controlling for stage, medical comorbidities, amount of blood transfused and allogeneic vs autologous blood, both studies found no difference in biochemical recurrence or overall survival amongst the groups of men investigated. It should be noted, however, that these were both non-randomized, observational studies, making it difficult to control for potential confounders that may have a significant impact on oncological outcomes.

Although the sample size of almost 11 000 subjects is robust, the present study is not without its limitations. As with any administrative data set, the results are subject to variability in the coding of complications such as blood transfusion. Additionally, the data set included information up until the fiscal year 2008. Subsequently, there has been a steady application of robotic PN for renal masses and this would certainly have an impact on a more contemporary cohort. Another important limitation is the lack of patient (preoperative haemoglobin values), intra-operative variables (complications, estimated blood loss) and tumour information, all of which could have had a significant impact on rates of PBT.

In conclusion, the transfusion rate after nephrectomy in general clinical practice is higher than that reported in the urological literature. Patient and provider factors appear to contribute to the considerable variability that exists in the observed transfusion rate. More specifically, in the present study, we observed that older patients and those with higher comorbidity had a greater probability of receiving a PBT, whereas those operated on by high volume surgeons and at high volume hospitals had a lower probability of receiving a PBT. A more detailed understanding of these factors may help with respect to preoperative patient counselling and informed consent.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Conflict of Interest
  8. References