Journal of Surgical Oncology 2009;99:508–512

Blood Loss in Surgical Oncology: Neglected Quality Indicator?

ELIJAH DIXON, MD, FRCSC, FACS,1* INDRANEEL DATTA, MD,1 FRANCIS R. SUTHERLAND, MD, FRCSC,1

AND JEAN-NICOLAS VAUTHEY, MD, FACS2

1Department of Surgery, Foothills Medical Centre, Calgary, Alberta, Canada2Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas

Quality indicators can be defined as ‘‘specific and measurable elements of practice that can be used to assess the quality of care’’. Surgical blood

loss is one of the most significant perioperative predictors of patient outcome. Blood loss is a modifiable quality indicator for oncologic cancer

surgery. Surgical oncologists need to alter their surgical technique to promote bloodless surgery and decrease the variability in reported blood loss

and rates of blood transfusion.

J. Surg. Oncol. 2009;99:508–512. � 2009 Wiley-Liss, Inc.

KEY WORDS: quality indicator; bloodloss; surgical oncology

INTRODUCTION

Quality indicators can be defined as ‘‘specific and measurable

elements of practice that can be used to assess the quality of care’’ [1].

Quality health care has been defined as ‘‘the degree to which health

services for individuals and populations increase the likelihood of

desired health outcomes and are consistent with current professional

knowledge’’ (Institute of Medicine). Quality indicators are important

for quality improvement, to compare performance at hospitals

over time, and as noted by Gagliardi et al. (2005) [1] to ‘‘set priorities

for the organization of medical care’’. This is in contradistinction to

practice guidelines, which are recommendations regarding evidence-

based best practices. Quality medical care as defined by Donabedian

[2] can be thought of as the interplay between structure, process, and

outcome. A good ‘‘quality indicator should define care that is

attributable and within the control of the person who is delivering

the care’’ (structure, process) [3], and is related to outcomes. Quality

indicators can also be divided into broad categories specific to surgical

care including surgical experience, preoperative assessment, patient

discussions, medications, intra-operative care and postoperative care

[4]. They are usually derived from retrospective reviews of medical

records. There are a number of ways to identify quality indicators

including the RAND/UCLA Appropriateness Methodology [1,5–7]

and Delphi processes. Both use best evidence and comprehensive

literature searches to derive a list of candidate quality indicators, along

with panels of experts that score potential quality indicators in the

context of an iterative process using consensus methodology to derive

the final list. To date, there is a paucity of quality indicators in surgical

oncology [1,8].

When McGory et al. (2006) [4] created quality indicators for

colorectal surgery they divided intra-operative indicators into staging

indicators, prevention of complication indicators, oncologic resection

criteria, and issues unique to laparoscopic surgery. Gagliardi et al. [1]

used a similar modified Delphi approach to develop quality indicators

for ovarian cancer. Specific surgical indicators included volume of

ovarian cancer surgery, proportion of cases operated on by gynecologic

oncologists, the percentage of patients who undergo optimal debulk-

ing, and appropriate staging laparatomy with peritoneal biopsies,

diaphragmatic assessment, and extensive lymphadenectomy. These

initial steps at identifying quality indicators are encouraging. Recently,

there have been a number of studies examining the number of lymph

nodes harvested for oncologic resections and their relationship to

outcomes. These studies have shown that there may be an association

with long-term survival and the number of lymph nodes retrieved for

gastric, colorectal, and pancreatic cancer. Strategies to measure quality

indicators and to adjust practice based on them are not well described

or established. In addition, it is clear that many surgeons are still

unaware of standards for many oncologic resections. Helyer et al.

(2007) [9] noted that only 16 out of 206 Ontario surgeons recognized

proximal gastric cancer margins of 5 cm and 15 lymph nodes on

lymphadenectomy as appropriate goals for resection.

To our knowledge the use of surgical blood loss as a quality

indicator in surgery, and specifically surgical oncology has not been

described. This review highlights the evidence for blood loss as a

quality indicator in surgical oncology, and outlines some strategies to

measure it, and to decrease operative blood loss.

BLOOD LOSS IN SURGERY

Bloodless surgery has been considered mainly in situations where

supplies are limited, for example trauma and war times, or in situations

where patient objections to transfusion may be present as in the case of

Jehovah’s Witnesses [10]. Current evidence suggests allogenic

transfusions are safe with regards to the transmission of infectious

agents, however, liberal use of transfusions may not be beneficial

[10,11]. Although current viral disease transmission risks are low, the

majority occur in the ‘‘window period’’ during which time a blood

donor is infectious but does not present positive on screening tests [12].

The estimated risk of viral infection transmission is approximately 1 in

200,000 for hepatitis B, 1 in 800,000 for hepatitis C, and approximately

1 in 1,400,000 for HIV [12]. Transfusion reactions are more common

with 1 in 8,000 patients developing transfusion-related acute lung

injury and hemolytic transfusion reactions ranging from 1 in 250,000

*Correspondence to: Elijah Dixon, MD, FRCSC, FACS, University ofCalgary, Tom Baker Cancer Centre, 1331-29th Street NW, Calgary, Alberta,Canada T2N 4N2. Fax: 1 403 521 3744.E-mail: elijah.dixon@calgaryhealthregion.ca

Received 15 September 2008; Accepted 29 September 2008

DOI 10.1002/jso.21187

Published online in Wiley InterScience(www.interscience.wiley.com).

� 2009 Wiley-Liss, Inc.

(acute) to nearly 1 in 1,000 (delayed) [12]. Bacterial contamination of

red blood cells is rare (1 in 500,000) with Yersinia enterocolitica being

the most common causative organism. However, platelet contamina-

tion can be as high as 1 in 2,000 [12]. Although much of the research

on Cytomegalovirus (CMV) infection with transfusions has been

completed on patients receiving allogenic bone marrow transplant,

CMV infection is also a concern for the immune-compromised surgical

oncology patient. However, only 10–50% of the blood donor

population is sero-negative for CMV [12]. Consequently, there is a

risk of seroconversion with transfusions. The overall risk of

seroconversion with transfusion may be as high as 1–4% [12].

In 1825, Dr. James Blundell a British physiologist and obstetrician

performed the first successful human blood transfusion [13]. Years

later, Dr. George Crile used blood transfusions intra-operatively. Since

its inception, there have been major advances in transfusion medicine.

In the late 1970s and throughout the 1980s and early 1990s it became

clear that allogenic blood transfusions can cause immunosupression.

This is most evident in the renal transplant and trauma literature. Opelz

and Terasaki (1978) [14] presented a retrospective study of 1,360

cadaveric kidney transplants, they showed there was a significant

improvement in graft survival at 1 and 4 years for recipients who

underwent transfusions. In fact, there was a staggering difference of

almost 30% in graft survival for patients with more than 20 transfusions

as compared to recipients without transfusions [14]. This influenced

subsequent studies looking at deliberate blood transfusions [15].

Salvatierra et al. (1980) [15] used deliberate donor specific blood

transfusions prior to living-related renal transplantation and found

improved graft survival. Also, Glass and colleagues documented a

4 year experience with donor blood transfusions [16] demonstrating

high actuarial 1 year graft survival rates at 93%. These findings were

further validated by Williams et al. (1980) [17] who showed 85% graft

survival at 1 year in patients who received two units of whole blood as

compared to 34% in patients not transfused.

Based on the transplant literature and observations of transfused

trauma patients there is concern regarding the risk of infectious

complications as a result of immunosuppression associated with blood

transfusions in trauma [18,19]. This is controversial as it is difficult to

ascertain whether it is the injury severity that increases the risk of

infection or the required blood transfusions given for resuscitation and

treatment of shock [18].

BLOOD TRANSFUSION AND MECHANISMSOF IMMUNOSUPPRESSION

Although there is evidence indicating immunosuppression results

from blood transfusions, the specific mechanisms are unclear. Most

likely the mechanisms are multi-factorial involving both leukocyte

components with changes in humoral and cell-mediated immunity

[20]. One study noted decreased lymphocyte proliferation with whole

blood transfusion versus leukocyte depleted blood in patients under-

going elective colorectal surgery [21]. They also noted a decrease in

the CD4þ:CD8þ ratio with whole blood transfusion [21]. This

translated to an increased incidence of postoperative infection [21].

Reduced natural killer T-cell function has also been linked with

immunosuppression [19,22]. In fact, a randomized trial by Jensen et al.

[23] measured natural killer T-cell function in three groups of patients;

no blood transfusions, whole blood transfusions, and filtered blood

transfusions (packed red blood cells). They noted a significant decrease

in natural killer T-cell function at 30 days in patients receiving blood

transfusions. Others argue that it is the blood loss that affects

immunity, separate from the affects of the transfusion [24]. This has

been demonstrated in animal models [25]. One study assessed

hemorrhage without tissue trauma or transfusion in a mice model

[25]. The mice were bled to a mean blood pressure of 35 mmHg and

kept at that pressure for 1 hr. Subsequently the proliferative response

of lymphocytes was measured using a mitogen stimulation assay.

Immunosuppression persisted for 5 days. A second aspect of the study

compared hemorrhagic to non-hemorrhagic mice in a sepsis model.

The sepsis model was created on the third day following hemorrhage

by isolating and perforating the cecum of the mice. The mortality

difference was 42% with a 100% mortality for in the group that

suffered hemorrhage versus only 58% of mice in the ‘‘sham’’

hemorrhage group [25]. Clearly, this animal model suggests reduced

immunity with hemorrhage alone [25].

BLOOD LOSS AND TRANSFUSIONS INSURGICAL ONCOLOGY

Research evaluating the affects of blood transfusions in surgical

oncology have shown conflicting results [26]. Some believe there is a

direct increase in cancer recurrence risk with blood transfusions

whereas others suggest transfusions are an indicator of overall poor

outcome irrespective of cancer recurrence [26]. The majority of studies

have been completed on the colorectal cancer population. Busch et al.

(1994) [27] evaluated 420 patients who underwent curative resection

for colorectal cancers. They noted a difference in local recurrence

(20 vs. 3%) indicating higher recurrence for patients receiving blood

transfusions. In addition, they found better disease free survival in

those patients not requiring transfusion (73 vs. 59%). However, Busch

et al. [27] found no difference in 4 year risk of having metastasis. The

same investigators noted no difference in prognosis when comparing

autologous and allogenic blood transfusions [28]. This may be because

autologous transfusions incite the same reaction as allogenic transfu-

sions. Nonetheless, both types of transfusion were associated with a

poorer prognosis. It may also be explained by the complexity of the

operation and other operative factors that led to the transfusion in the

first place [28]. Others have shown that both whole blood and

leukocyte depleted blood transfusions had increased postoperative

ventilation rates and prolonged hospital stay [29]. Another study also

noted a 5 year survival difference with 72.9 and 59.6% (P< 0.001),

respectively for patients not transfused versus those transfused, the

cancer recurrence rate was not significantly different [30]. Further

evidence was provided recently by Miki et al. (2006) [31] who assessed

perioperative allogenic blood transfusions and the relation of cytokine

response to long-term survival in colorectal cancer patients. In this

study patients were categorized into two groups; the first group was

composed of patients who received blood transfusions preoperatively

for chronic anemia and the second group included patients who received

blood transfusions for excessive blood loss intra-operatively [31]. The

group that received transfusions for blood loss had increased interleukin

(IL)-6 and tumor growth factors and a poorer prognosis [31].

There are few other studies available investigating blood transfu-

sions in surgery for malignancy. One study published in 1989 was

completed on breast cancer patients [32]. This group prospectively

evaluated 812 patients with both node positive and negative breast

cancer. Patients requiring transfusions had similar preoperative

hemoglobin levels and hematocrit values indicating transfusions were

required for intra-operative bleeding and not for chronic anemia [32].

Patients with node negative breast cancer who required transfusion had

both decreased disease free intervals and overall survival [32]. These

results were most dramatic in patients who required two or more units

of blood perioperatively where the 5 year overall survival was 85%

(transfused patients) as compared to 93% in patients not transfused

(P¼ 0.04) [32].

The perioperative and long-term effects of blood transfusions

on patients undergoing hepatic resection for colorectal metastases

was retrospectively evaluated by Kooby et al. [33]. They found that

blood transfusions in the perioperative period were associated with

Journal of Surgical Oncology

Blood Loss Surgical Oncology Quality Indicator 509

higher complication rates, longer hospital length of stay, and early

mortality [33].

Chen et al. [34] looked at 30 allogenic transfused patients as

compared to 30 autologous transfused patients undergoing gastric

cancer resection with curative intent. They demonstrated a more

substantial drop in T-cell subsets in patients with allogenic transfusions

[34]. Currently there are no large randomized prospective trials

assessing blood transfusions and overall and disease specific mortality

in gastric, breast, lung, prostate, or renal cell cancer, however,

retrospective reviews suggest poorer overall survival with blood

transfusions in these groups [35–39]. Results of large studies

evaluating the effects of blood transfusions in patients undergoing

oncologic resections is shown in Table I.

STRATEGIES TO MEASURE AND MINIMIZESURGICAL BLOOD LOSS

The evidence strongly suggests that significant operative blood loss

along with the accompanying need for blood transfusion in the surgical

oncology patient has major deleterious effects with respect to both

short- and long-term patient outcomes. The exact mechanism leading

to these poor outcomes are likely multi-factorial. High operative blood

loss may be partially explained by technically challenging oncologic

resections, and be a surrogate for locally advanced tumors exhibiting

an aggressive cancer biology. However, high operative blood loss can

also obscure the operative field, and impair the surgeon’s ability

to perform precise anatomic oncologic resections. The technical

challenges resulting from a surgical procedure with high blood loss

along with the immunosuppressive effects of the resulting blood

transfusions combine together to significantly impair the cancer

patient’s outcomes—both in the short- and long-term. Surgical blood

loss is one of the most significant perioperative predictors of patient

outcome that is modifiable and within the control of the cancer

surgeon. For this reason, it is imperative that we as cancer surgeons

measure our perioperative estimated blood loss in a valid manner, and

take measures to minimize surgical bleeding and thereby improve our

patients’ outcomes.

To date, there is very little investigating methods of surgical

oncology measuring and reporting surgical blood loss in a valid and

reproducible manner have been reported. In fact, most assessments of

blood loss are subjective estimations made by either the surgeon or

anesthesiologist [40]. Measurement of sponge weights or the volume of

fluid in suction containers is highly inaccurate and do not account

accurately for irrigation and third space losses. Some surgeons measure

transfusion rates, however, the indication for transfusion can be

variable, particularly depending on surgeon preference and anticipa-

tion of blood loss by the anesthesia team [40]. One better option is to

calculate the estimated blood volume (EBV) preoperatively and then

after surgery and calculate the difference. First described by Gross

in 1983, the EBV is determined using the patient’s height, weight,

and gender [40,41]

EBV ¼height0:781 � weight0:427� �

10; 000� 74:49 � 2:74 for males

2:37 for females

�

Using the EBV the calculated blood loss (CBL) can also be

determined by noting the difference in preoperative and postoperative

hemoglobin values [40]

CBL ¼2EBV Hgpreop � Hgpostop

� �Hgpreop þ Hgpostop

The CBL can also be adjusted based on the number of transfusions

received by adding 450 ml per unit transfused [40]. By using this

calculation of blood loss at our own institution, we identified 65%

greater actual blood loss then our initial estimate [40]. This estimate of

blood loss incorporates transfusions and blood lost at the time of surgery

[40]. In addition, it provides an estimate appropriate for the size of the

patient and is consequently a superior calculation of blood loss.

The measurement of CBL should become routine for all cancer

operations along with the rates of blood transfusion. These measure-

ments should be part of surgical oncology databases. The CBL and

blood transfusion rates for different surgical procedures should be

reported. This will allow comparison between institutions and surgeons,

which will provide the impetus for quality improvement initiatives. The

CBL and rates of blood transfusion for different surgical procedures

are robust quality indicators. They provide a link between processes of

care and outcomes for cancer surgery patients. Importantly, they are

modifiable risk factors for poor short- and long-term outcomes. There

are high degrees of variation in estimated blood loss and rates of blood

Journal of Surgical Oncology

TABLE I. Effect of Blood Transfusions on Oncologic Resections

Author (year) Study design n Tumor type Effect of transfusion Outcome

Frankish et al. (1985) RCT 174 Colorectal No effect No difference in 3 year overall survival

Houbiers et al. (1994)

[41]

RCT 697 Colorectal Negative Lower 3 year survival, higher infection

rate. No difference in cancer

recurrence

Tartter (1992) RCT 339 Colorectal Negative Decreased 5 year survival and increased

tumor recurrence with transfusion

Heiss et al. (1995) RCT 120 Colorectal Negative Increased risk of tumor recurrence with

allogenic blood transfusion

Busch et al. (1993) RCT 475 Colorectal Negative No statistical difference between

allogenic and autologous transfusions.

Both types of transfusion have

increased risk of recurrence

Kooby et al.(2003) Retrospective review 1,351 Hepatic resection

for colorectal

cancer

Negative Transfusion is an independent risk factor

for perioperative mortality, length of

stay and complications.

Crowe et al. (1989) RCT 812 Breast Negative Poorer disease free interval and overall

survival with transfusion in node

negative patients

Ness et al.(1992) Retrospective review 309 Prostate No effect No difference in local recurrence of

prostate cancer

510 Dixon et al.

transfusion in the reported literature for almost all surgical oncology

procedures. This highlights the fact that there are inaccuracies in

the measurement of CBL, and differences in surgical techniques

to minimize blood loss between surgeons and institutions. Surgical

oncologists need to measure them routinely, and take action to decrease

perioperative blood loss and the concomitant blood transfusions that

accompany blood loss. Historically, there has been little discussion

around blood loss and rates of blood transfusion recognizing that it is a

modifiable perioperative quality indicator. This needs to be changed.

Perioperative approaches to minimize blood loss are paramount.

There are strategies to minimize blood loss developed for use in patients

unwilling to accept autologous blood transfusion, as is the case with

patients who are Jehovah’s Witnesses. These can be categorized as

preoperative, intra-operative, and postoperative management strategies

[10]. Preoperative management options include improvement in

hemoglobin levels using both exogenous iron treatment and erythro-

poietin [10,42]. In addition, steps can be taken to reduce the number of

blood tests performed on patients preoperatively and care should be

taken to ensure discontinuation of pharmaceutical agents that can affect

the coagulation cascade [10]. Intra-operative options used regularly

when operating on Jehovah’s Witness patients include reduction in

central venous pressures, the use of electrocautery, tourniquets, and the

mechanical occlusion of major vessels (i.e., Pringle maneuver) [10].

Also, surgeons can employ the use of topical hemostatic agents and

employ the use of autologous blood cell salvage devices and accept

normovolemic hemodilution when significant bleeding is anticipated

[10,42]. Blood cell salvage devices can be used intra-operatively in

Jehovah’s Witness patients only if the circuit remains in continuity with

the patient [42]. Postoperatively, early detection of bleeding complica-

tions, and tolerance of anemia with restrictive use of transfusions are

both possible employable strategies [10,11].

Significant reductions in blood loss are often possible with simple

changes to surgical technique. If the operating surgeon decides that

blood loss will not be accepted, stops all bleeding as it occurs—

including ‘‘minor’’ bleeding from wound edges and the planes of

dissection, this alone will often significantly reduce operative blood

loss, especially in complex procedures with multiple steps (i.e.,

Whipple operation, multivisceral oncologic resections). This takes a

change in surgical approach and affects the conduct of the operation.

This includes minimizing the use of ‘‘blunt’’ dissection by the surgeon,

and instead should be replaced by precise dissection under direct vision

along embryologic tissue planes where possible. Many of these

techniques have been developed in the field of solid organ

transplantation, surgery for, or in the patient with portal hypertension,

and from the living donor hepatectomy operation largely pioneered in

Japan [43]. Careful surgical technique using precise techniques of

dissection with electrocautery aimed at minimizing blood will

significantly reduce bleeding during surgical resections. This attention

to intra-operative surgical technique with careful dissection and

hemostasis, use of electrocautery, and maintenance of normothermia

can reduce the need for transfusions [10].

It is clear that CBL can and should be used as a quality indicator.

Blood transfusions result in immunosuppression and increased

morbidity and may impair long-term oncologic outcomes. Blood loss

is a modifiable quality indicator for oncologic cancer surgery. Surgeons

need to measure and report CBL and rates of blood transfusion.

Surgical oncologists need to alter their surgical technique to promote

bloodless surgery and decrease the variability in reported blood loss

and rates of blood transfusion.

REFERENCES

1. Gagliardi AR, Fung MF, Langer B, et al.: Development of ovariancancer surgery quality indicators using a modified Delphiapproach. Gynecol Oncol 2005;97:446–456.

2. Donabedian A: The quality of care. How can it be assessed? Jama1988;260:1743–1748.

3. Marshall M, Campbell C, Hacker J, et al.: Quality indicators forgeneral practice. London: Royal Society of Medicine; 2002.

4. McGory ML, Shekelle PG, Ko CY: Development of qualityindicators for patients undergoing colorectal cancer surgery.J Natl Cancer Inst 2006;98:1623–1633.

5. Gagliardi AR, Fleshner N, Langer B, et al.: Development ofprostate cancer quality indicators: a modified Delphi approach.Can J Urol 2005;12:2808–2815.

6. Gagliardi AR, Simunovic M, Langer B, et al.: Development ofquality indicators for colorectal cancer surgery, using a 3-stepmodified Delphi approach. Can J Surg 2005;48:441–452.

7. Malin JL, Asch SM, Kerr EA, et al.: Evaluating the quality ofcancer care: development of cancer quality indicators for a globalquality assessment tool. Cancer 2000;88:701–707.

8. Porter GA, Skibber JM: Outcomes research in surgical oncology.Ann Surg Oncol 2000;7:367–375.

9. Helyer LK, O’Brien C, Coburn NG, et al.: Surgeons’ knowledgeof quality indicators for gastric cancer surgery. Gastric Cancer2007;10:205–214.

10. Goodnough LT, Shander A, Spence R: Bloodless medicine:clinical care without allogeneic blood transfusion. Transfusion2003;43:668–676.

11. Hebert PC, Wells G, Blajchman MA, et al.: A multicenter,randomized, controlled clinical trial of transfusion requirementsin critical care. Transfusion Requirements in Critical CareInvestigators, Canadian Critical Care Trials Group. N Engl JMed 1999;340:409–417.

12. Goodnough LT: Risks of blood transfusion. Crit Care Med2003;31:S678–686.

13. Baskett TF: James Blundell: the first transfusion of human blood.Resuscitation 2002;52:229–233.

14. Opelz G, Terasaki PI: Improvement of kidney-graft survival withincreased numbers of blood transfusions. N Engl J Med1978;299:799–803.

15. Salvatierra O Jr, Vincenti F, Amend W, et al.: Deliberate donor-specific blood transfusions prior to living related renal trans-plantation. A. new approach. Ann Surg 1980;192:543–552.

16. Glass NR, Miller DT, Sollinger HW, et al.: A four-year experiencewith donor blood transfusion protocols for living-donor renaltransplantation. Transplantation 1985;39:615–619.

17. Williams KA, Ting A, French ME, et al.: Peroperative blood-transfusion improve cadaveric renal-allograft survival in non-transfused recipients. A. prospective controlled clinical trial.Lancet 1980;1:1104–1106.

18. Agarwal N, Murphy JG, Cayten CG, et al.: Blood transfusionincreases the risk of infection after trauma. Arch Surg1993;128:171–176 discussion 176–177.

19. Hill GE, Frawley WH, Griffith KE, et al.: Allogeneic bloodtransfusion increases the risk of postoperative bacterial infection:a meta-analysis. J Trauma 2003;54:908–914.

20. Nielsen HJ: Detrimental effects of perioperative blood trans-fusion. Br J Surg 1995;82:582–587.

21. Jensen LS, Hokland M, Nielsen HJ: A randomized controlled studyof the effect of bedside leucocyte depletion on the immunosup-pressive effect of whole blood transfusion in patients undergoingelective colorectal surgery. Br J Surg 1996;83:973–977.

22. Borleffs JC, Marquet RL, de By-Aghai Z, et al.: Kidneytransplantation in rhesus monkeys. Matching for D/DR antigens,pretransplant blood transfusions, and immunological monitoringbefore transplantation. Transplantation 1982;33:285–290.

23. Jensen LS, Andersen AJ, Christiansen PM, et al.: Postoperativeinfection and natural killer cell function following blood trans-fusion in patients undergoing elective colorectal surgery. Br JSurg 1992;79:513–516.

24. Busch OR, Hop WC, Marquet RL, et al.: Prognostic impact ofblood transfusions on disease-free survival in colorectal carci-noma. Scand J Gastroenterol Suppl 1993; 20021–20023.

25. Stephan RN, Kupper TS, Geha AS, et al.: Hemorrhage withouttissue trauma produces immunosuppression and enhances sus-ceptibility to sepsis. Arch Surg 1987;122:62–68.

Journal of Surgical Oncology

Blood Loss Surgical Oncology Quality Indicator 511

26. McAlister FA, Clark HD, Wells PS, et al.: Perioperativeallogeneic blood transfusion does not cause adverse sequelae inpatients with cancer: a meta-analysis of unconfounded studies. BrJ Surg 1998;85:171–178.

27. Busch OR, Hop WC, Marquet RL, et al.: Blood transfusions andlocal tumor recurrence in colorectal cancer. Evidence of anoncausal relationship. Ann Surg 1994;220:791–797.

28. Busch OR, Hop WC, Hoynck van Papendrecht MA, et al.: Bloodtransfusions and prognosis in colorectal cancer. N Engl J Med1993;328:1372–1376.

29. Skanberg J, Lundholm K, Haglind E: Effects of blood transfusionwith leucocyte depletion on length of hospital stay, respiratoryassistance and survival after curative surgery for colorectalcancer. Acta Oncol 2007;46:1123–1130.

30. van de Watering LM, Brand A, Houbiers JG, et al.: Perioperativeblood transfusions, with or without allogeneic leucocytes, relateto survival, not to cancer recurrence. Br J Surg 2001;88:267–272.

31. Miki C, Hiro J, Ojima E, et al.: Perioperative allogeneic bloodtransfusion, the related cytokine response and long-term survivalafter potentially curative resection of colorectal cancer. ClinOncol (R Coll Radiol) 2006;18:60–66.

32. Crowe JP, Gordon NH, Fry DE, et al.: Breast cancer survival andperioperative blood transfusion. Surgery 1989;106:836–841.

33. Kooby DA, Stockman J, Ben-Porat L, et al.: Influence oftransfusions on perioperative and long-term outcome in patientsfollowing hepatic resection for colorectal metastases. Ann Surg2003;237:860–869. discussion 869–870.

34. Chen G, Zhang FJ, Gong M, et al.: Effect of perioperativeautologous versus allogeneic blood transfusion on the immune

system in gastric cancer patients. J Zhejiang Univ Sci B 2007;8:560–565.

35. Fong Y, Karpeh M, Mayer K, et al.: Association of perioperativetransfusions with poor outcome in resection of gastric adeno-carcinoma. Am J Surg 1994;167:256–260.

36. Hyman NH, Foster RS Jr, DeMeules JE, et al.: Blood transfusionsand survival after lung cancer resection. Am J Surg 1985;149:502–507.

37. Little AG, Wu HS, Ferguson MK, et al.: Perioperative bloodtransfusion adversely affects prognosis of patients with stage Inon-small-cell lung cancer. Am J Surg 1990;160:630–632.discussion 633.

38. Manyonda IT, Shaw DE, Foulkes A, et al.: Renal cell carcinoma:blood transfusion and survival. Br Med J (Clin Res Ed) 1986;293:537–538.

39. Moores DW, Piantadosi S, McKneally MF: Effect of perioperativeblood transfusion on outcome in patients with surgically resectedlung cancer. Ann Thorac Surg 1989;47:346–351.

40. Sutherland F, Mackenzie S, Bathe O, et al.: Measuring blood lossduring hepatectomy. HPB (in press).

41. Gross JB: Estimating allowable blood loss: corrected for dilution.Anesthesiology 1983;58:277–280.

42. Gohel MS, Bulbulia RA, Slim FJ, et al.: How to approachmajor surgery where patients refuse blood transfusion(including Jehovah’s Witnesses). Ann R Coll Surg Engl 2005;87:3–14.

43. Fujita S, Kim ID, Uryuhara K, et al.: Hepatic grafts from livedonors: donor morbidity for 470 cases of live donation. TransplInt 2000;13:333–339.

Journal of Surgical Oncology

512 Dixon et al.