In the past two decades, allogenic blood transfusion has been associated with multiple complications, and thus treatment strategies to decrease perioperative blood loss are of interest to orthopaedic surgeons treating patients with hypervascular skeletal metastases [8, 9, 13, 18]. Preoperative transarterial embolization has been utilized in the treatment of osseous metastatic disease for several decades with case reports dating back to the 1970s [3, 4, 7, 14, 20, 23]. Since these initial reports, the procedure has gained widespread acceptance and has been applied preoperatively in an attempt to minimize perioperative blood loss and transfusion use in patients with metastatic disease of the long bones [1, 2, 15, 17]. The current study identified a large cohort of patients with metastatic renal cell carcinoma of the femur who underwent prophylactic fixation and compares utilization of blood transfusion between a group of patients who underwent preoperative embolization and a group of patients who did not undergo embolization. In the study population, 69% of patients received no blood transfusions in the first 7 postoperative days. With the numbers available, there was no difference in transfusion percentages between the study groups, with 31% of the control group receiving one or more units of blood and 30% of the embolization group.
There are several limitations of the current study. Given the nonrandomized nature of the study, selection bias may have been introduced, with patients believed most likely to experience high perioperative blood loss being more likely to be included in the embolization group. This would bias the results such that an ability to detect a major reduction in transfusion rates between intervention and control groups would be diminished. The volume of blood transfused cannot be reported as a result of the database design of the study. Specifically, it is possible that the overall volume of blood transfused per patient in the embolization group was lower than in the control group. This is a critically important limitation to the data, and it should be emphasized that the results from the current study would not justify abandonment of preoperative embolization altogether as a strategy to decrease blood loss, especially for patients who are at high risk for perioperative blood loss, perhaps including those with large tumors or low preoperative hemoglobin. Acknowledging this important limitation, the authors believe the key clinical message from the study is that 69% of the patients who had surgery without preoperative embolization received no transfusions at all, suggesting that preoperative embolization may not be mandatory in all patients undergoing prophylactic treatment for renal cell metastases. Unfortunately from this database, we cannot identify the characteristics of the patients who did not receive embolization. This subgroup of the study population emphasizes the need for further research that can delineate which patients are most and least likely to benefit from embolization.
Other clinically important complications and benefits of preoperative embolization such as length and difficulty of surgery cannot be assessed with the current study design. The study cannot identify which patients received radiation or chemotherapy. The current study relies on coding to identify patients, and these codes may have been established by professional coders, not treating physicians. The degree of agreement between coders and treating physicians in this study population has not been reported, and confirmation with chart review is not possible. We could not control for the criteria for using blood transfusions in these patients and it is well known that indications for transfusion have changed over time and likely vary between different physicians and centers. Preexisting medical conditions in addition to surgical blood loss might have influenced the use of transfusion from the surgical procedure or there may have been other reasons for transfusion such as bleeding from other causes. The Medicare database used in this study relies on ICD-9 procedural codes for inpatient procedures, and differentiation between intramedullary nailing and other means of prophylactic fixation is not possible. However, it is assumed that the majority of patients who underwent prophylactic fixation in this study were treated with intramedullary nailing. The database design of the current study limits characterization of patient, tumor, and surgical variables, including preoperative hemoglobin, utilization of curettage intraoperatively, and tumor size, all of which may contribute to transfusion and blood loss in surgical treatment of femur fractures [11, 15, 16, 19]. This implicit limitation further limits the capacity for direct comparisons between the studies.
No difference in the proportion of patients who received transfusions was observed between the embolization group and the control group. Findings from this study are in agreement with those of Pazionis et al. relating to the lack of demonstrated benefit of preoperative transarterial embolization in femoral intramedullary nailing procedures . The extent to which preoperative embolization decreases perioperative blood loss and transfusion remains controversial. Given the widespread acceptance and utilization of transarterial embolization in the treatment of osseous metastatic disease, many studies have not included control groups [1, 20, 21]. There are, however, several studies examining patients with metastatic long bone disease comparing results of transarterial embolization with control groups without transarterial embolization (Table 3) [1, 15, 17]. In their 1989 study, Roscoe et al.  reported a decrease in estimated blood loss in 10 patients with metastatic renal cell carcinoma of the femur who underwent preoperative transarterial embolization relative to 20 historical control subjects at their institution who did not undergo transarterial embolization. The rate of transfusion and mean volume transfused were not reported. Barton et al.  published results from 61 transarterial embolization procedures involving 36 patients with metastatic renal cell carcinoma. In their series, three patients had metastatic disease to the femur. Their overall results demonstrated a reduction in estimated blood loss in the transarterial embolization group compared with 20 historical control subjects from their institution. Neither rate of transfusion nor volume of transfused blood was reported. A recent well-designed, case-control study by Pazionis et al.  compared patients who underwent preoperative transarterial embolization with closely matched control subjects. Notably, the population in their study consisted of patients in whom the use of transarterial embolization was controversial with patients most likely and least likely to benefit from the procedure excluded from their analysis. They noted decreased estimated blood loss, volume of blood transfused, and operative time in the subgroup analysis of 14 patients with femoral disease undergoing open procedures. In the subgroup analysis of 16 patients with femoral disease who underwent femoral nailing, no reduction in transfusion volume was demonstrated .
The clinical utility of the current study is that it demonstrates that preoperative embolization may not be mandatory in the prophylactic treatment of metastatic renal cell carcinoma of the femur. This is demonstrated by the 69% of 1150 patients treated with prophylactic femur fixation who did not receive embolization and received no blood transfusions at all. These data suggest that the determination of whether a patient with renal cell metastases to bone should undergo preoperative embolization should be made on a case-by-case basis. The current study does not identify specific risk factors that should factor into this decision and underscores the need for further research in this regard. A plausible future research design to account for the selection bias and other data limitations that plague the current study as well as the existing literature would be a multicenter retrospective case-control study, which would allow a larger volume of patients than the existing literature and increased patient-specific detail than the current study. Such a study should include pathologic fractures in addition to femurs treated prophylactically. Important variables including tumor size, preoperative hemoglobin and platelet levels, medical comorbidities, and surgical treatment variables could be included in the data set and corrected for in the analysis. Such a study could identify and quantify risk factors that would help to target which patients may benefit most from embolization. Ideally, identification and quantification of these risk factors would allow for creation of a clinically useful scoring system that could be rapidly applied preoperatively to determine which patients are most likely to benefit from preoperative embolization.
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