Reamer/Irrigator/Aspirator (RIA) and Intramedullary Fixation for Impending Pathologic Femur Fracture
John W. Munz, MD¹, Andrea L. Gale, MD²; Rex A. W. Marco, MD²
¹Department of Orthopaedic Surgery, The University of Texas Health Science Center at Houston; Houston, TX
²Department of Orthopedic Surgery, Houston Methodist Hospital; Houston, TX
Corresponding Author:Rex A. W. Marco, MD. Department of Orthopedic Surgery, Houston Methodist Hospital, 6550 Fannin St., Houston, TX 77030, USA; rexmarco@gmail.com
DOI: 10.18600/toj.010205
INTRODUCTION
Each year in the United States over 1.4 million new carcinomas are diagnosed. It has been estimated that between 50% and 80% of patients will have bony metastases at the time of death [1]. Most metastatic carcinomas to bone will originate in the breast, prostate, lung, kidney, thyroid, and gastrointestinal tract, in decreasing frequency. Pathologic femur fractures are significant sequelae of metastatic carcinomas and multiple myeloma [2].
Once fractures occur, patients suffer increased morbidity and mortality. Although the prognosis for patients with metastatic carcinomas or multiple myeloma continues to improve, survivability remains highly unpredictable. Regardless of treatment, the common objective is to perform one operation that allows immediate weight bearing, yet is durable throughout the patient’s remaining lifetime. Current treatment options include large resections with prosthetic reconstruction, open curettage with cement/allograft/autograft reconstruction, and closed intramedullary stabilization. These operations differ in magnitude and some require extensive recovery and rehabilitation with lengthy hospital stays. Most patients with impending fractures have limited life expectancy, and an extensive postoperative recovery can drastically reduce the quality of remaining life.
For impending pathologic fractures involving the subtrochanteric, diaphyseal, and metadiaphyseal regions of the femur, closed intramedullary fixation has been shown to be a viable and beneficial treatment modality [3-7]. Although having the benefits of immediate weight bearing (load sharing), stabilization of the entire bone, and relative ease in application [8], there are still concerns with this form of treatment. These concerns include spread of tumor down the medullary canal of the femur, pulmonary complications [9], neurologic complications [10,11], hardware failure [5], and lack of tumor debulking. The concerns are especially significant in this particular patient population with multiple systemic abnormalities from metastatic disease.
The purpose of this study was to evaluate the use of the Reamer/Irrigator/Aspirator (RIA; Synthes, Paoli, PA, USA) with intramedullary prophylactic fixation in impending subtrochanteric, diaphyseal, and metadiaphyseal femur fractures. Use of RIA is currently our protocol in management of these lesions. This device is used in place of traditional reamers, taking advantage of its irrigating and suction characteristics. The RIA is used to function as a type of “closed curettage” to aid in tumor debulking while also allowing the use of larger-diameter implants for stabilization. Also, the suctioning capabilities can potentially limit the amount of systemic embolization of fat and tumor, thereby potentially reducing pulmonary sequelae. We present a technique using the RIA in the treatment of impending pathologic femur fractures.
Each year in the United States over 1.4 million new carcinomas are diagnosed. It has been estimated that between 50% and 80% of patients will have bony metastases at the time of death [1]. Most metastatic carcinomas to bone will originate in the breast, prostate, lung, kidney, thyroid, and gastrointestinal tract, in decreasing frequency. Pathologic femur fractures are significant sequelae of metastatic carcinomas and multiple myeloma [2].
Once fractures occur, patients suffer increased morbidity and mortality. Although the prognosis for patients with metastatic carcinomas or multiple myeloma continues to improve, survivability remains highly unpredictable. Regardless of treatment, the common objective is to perform one operation that allows immediate weight bearing, yet is durable throughout the patient’s remaining lifetime. Current treatment options include large resections with prosthetic reconstruction, open curettage with cement/allograft/autograft reconstruction, and closed intramedullary stabilization. These operations differ in magnitude and some require extensive recovery and rehabilitation with lengthy hospital stays. Most patients with impending fractures have limited life expectancy, and an extensive postoperative recovery can drastically reduce the quality of remaining life.
For impending pathologic fractures involving the subtrochanteric, diaphyseal, and metadiaphyseal regions of the femur, closed intramedullary fixation has been shown to be a viable and beneficial treatment modality [3-7]. Although having the benefits of immediate weight bearing (load sharing), stabilization of the entire bone, and relative ease in application [8], there are still concerns with this form of treatment. These concerns include spread of tumor down the medullary canal of the femur, pulmonary complications [9], neurologic complications [10,11], hardware failure [5], and lack of tumor debulking. The concerns are especially significant in this particular patient population with multiple systemic abnormalities from metastatic disease.
The purpose of this study was to evaluate the use of the Reamer/Irrigator/Aspirator (RIA; Synthes, Paoli, PA, USA) with intramedullary prophylactic fixation in impending subtrochanteric, diaphyseal, and metadiaphyseal femur fractures. Use of RIA is currently our protocol in management of these lesions. This device is used in place of traditional reamers, taking advantage of its irrigating and suction characteristics. The RIA is used to function as a type of “closed curettage” to aid in tumor debulking while also allowing the use of larger-diameter implants for stabilization. Also, the suctioning capabilities can potentially limit the amount of systemic embolization of fat and tumor, thereby potentially reducing pulmonary sequelae. We present a technique using the RIA in the treatment of impending pathologic femur fractures.
MATERIALS & METHODS
After obtaining Institutional Review Board approval, we retrospectively reviewed all patients who met study inclusion and exclusion criteria. The inclusion criteria were impending pathologic femur fracture (Mirels score of 9 or greater) due to metastatic carcinoma or multiple myeloma (Table 1) [12], location of impending fracture in the subtrochanteric, diaphyseal, or metadiaphyseal region (Figure 1), and stabilization with intramedullary fixation. We excluded all patients with pathologic fractures, primary bone tumors, and patients with pertrochanteric involvement. Data collected included age, sex, location of lesion, pathology, number of lesions, presence of lung metastasis, presence of brain metastasis, type of pain, estimated blood loss, operative time, implant size, ASA class, Mirels score, intraoperative complications, length of hospital stay, discharge disposition, perioperative complications within 30 days, survival, ambulation method, pain relief (visual analog scale), duration of follow-up, hardware failure, and status of healing. Patients were followed up in clinic at 2, 6, 12, 24 weeks. In cases of absent follow-up, telephone interviews were conducted. All patients per protocol received postoperative radiation therapy.
Operative Technique
All patients were managed using a fracture table for supine positioning with intraop- erative fluoroscopic assistance. Implants included the RIA and the Trochanteric Fixation Nail, TFN (Synthes; Paoli, PA, USA). A closed intramedullary technique was utilized with a standard incision approximately 5 cm proximal to the greater trochanter. Entrance to the intramedullary canal was established with a threaded guide pin under fluoroscopic guidance at an angle 6 degrees off of the tip of the greater trochanter. After entry was gained into the intramedullary canal with a 10-mm entry reamer, a ball-tipped guide wire was passed to the level of the lesion. Prior to placement of the guide wire, a 20-degree bend was placed at the tip of the wire to help facilitate the reaming process. The guide wire was not advanced past the area of concern, but was used to facilitate tumor aspiration with the RIA under fluoroscopic control. Multiple passes of the RIA at the level of the lesion were performed to maximize tumor removal. Care was used not to pass the guide wire extramedullary during the reaming process. After thorough tumor debulking with multiple passes, the guide wire was then passed distally to aid in intramedullary device placement. The selected intramedullary device was then placed in standard fashion with locking into the femoral head, with proper placement confirmed using fluoroscopic guidance. A center-center position in the femoral head was used. Distal interlocking was performed using a free-hand technique. One or two distal interlocking screws were placed (Figure 2). Wound closure was completed in layers to prevent any fluid collection or medullary extravasation. All intramedullary reamings collected during reaming were sent to pathology for cytopathologic evaluation.
All patients were managed using a fracture table for supine positioning with intraop- erative fluoroscopic assistance. Implants included the RIA and the Trochanteric Fixation Nail, TFN (Synthes; Paoli, PA, USA). A closed intramedullary technique was utilized with a standard incision approximately 5 cm proximal to the greater trochanter. Entrance to the intramedullary canal was established with a threaded guide pin under fluoroscopic guidance at an angle 6 degrees off of the tip of the greater trochanter. After entry was gained into the intramedullary canal with a 10-mm entry reamer, a ball-tipped guide wire was passed to the level of the lesion. Prior to placement of the guide wire, a 20-degree bend was placed at the tip of the wire to help facilitate the reaming process. The guide wire was not advanced past the area of concern, but was used to facilitate tumor aspiration with the RIA under fluoroscopic control. Multiple passes of the RIA at the level of the lesion were performed to maximize tumor removal. Care was used not to pass the guide wire extramedullary during the reaming process. After thorough tumor debulking with multiple passes, the guide wire was then passed distally to aid in intramedullary device placement. The selected intramedullary device was then placed in standard fashion with locking into the femoral head, with proper placement confirmed using fluoroscopic guidance. A center-center position in the femoral head was used. Distal interlocking was performed using a free-hand technique. One or two distal interlocking screws were placed (Figure 2). Wound closure was completed in layers to prevent any fluid collection or medullary extravasation. All intramedullary reamings collected during reaming were sent to pathology for cytopathologic evaluation.
RESULTS
Between April 2007 and May 2009, we used this technique on 8 patients with impending pathologic femur fracture. There were 7 females and 1 male with a mean age of 61.5 years (range 34-74 years). The pathology consisted of one colon, one breast, one renal cell, one squamous cell, and two non-small cell lung carcinomas and two cases of multiple myeloma. The lesion locations included 3 subtrochanteric, 2 diaphyseal, 1 distal third, and 2 entire femoral shaft. Seven of the lesions were lytic, and 1 mixed. All patients presented with rest pain and the average Mirels score was 11 (range 10-12). ASA classification was evenly divided, with 4 patients assigned class 3 and 4 patients given class 4 preoperatively. Pulmonary metastases were present in 6 patients, and brain metastases were present in 5 patients.
Operative time averaged 62.3 minutes (range 31-133 minutes). The estimated blood loss averaged 212.5 ml (range 100-600 ml). Implant diameters ranged from 11-14 mm with RIA diameters ranging from 12-15 mm. No intraoperative complications occurred. Postoperatively, hospital length of stay averaged 9.1 days (range 2-24 days), with discharge disposition to rehabilitation in 3 patients, home in 4, and skilled nursing facility in 1 patient. Perioperative (30-day) complications included chemotherapy reaction, ileus, vaginal bleeding, and thrombocytopenia. No patients had a decline in pulmonary or neurologic status in the perioperative period. Seven patients were allowed full weight bearing immediately postoperatively with assistive devices; the remaining patient was kept partial weight bearing secondary to extensive femoral involvement by 11 separate lesions. Pain relief by visual analog scale averaged 9 preoperatively and was decreased to 2 postoperatively. The patients were followed up for a mean of 24.2 months (range 13-37 months). No implant failures had occurred at most recent follow-up. Overall survival averaged 10.1 months (range 2-23 months). Three patients are currently living with 19.3 months average follow-up, with 5 patients having since died with 4.6 months average follow-up. DISCUSSION
Closed, reamed intramedullary fixation for impending pathologic femur fractures is a powerful tool for achieving immediate stability; however, some important potential concerns exist. The first is the limited amount of tumor debulking that can be accomplished with standard reaming. The RIA technique provides simultaneous reaming, irrigation, and aspiration, which probably provides more tumor removal than standard reaming. More traditional open approaches with curettage and cement augmentation provide the most extensive debulking. However, open curettage requires a more extensive approach, which probably increases the risks of infection, blood loss, and operative time. Admittedly, the exact amount of tumor debulking is not known; however, in this limited series, no implant failures related to local tumor recurrence were noted, compared with reported rates of up to 21%. All patients had radiotherapy postoperatively to the entire femoral field.
Another concern is the potential pulmonary and neurologic dysfunction that can result from reamed instrumentation of the femoral canal. This can in particular be true for patients with preoperative pulmonary compromise of function from metastatic disease. Fat embolism syndrome is typically characterized by mental confusion, hypoxia, and a petechial rash. Previous authors have shown that patients with pathologic femur fractures are at a higher risk for the development of this condition [8]. Other authors have examined venting the canal during intramedullary reaming but the significance in the oncologic population has yet to be elucidated [12-14]. Use of the RIA in animal models has demonstrated lower numbers of pulmonary emboli and lower intramedullary pressures when compared with traditional reaming [15,16]. In our small series, 6 patients had pulmonary metastases and compromised lung function, while 5 patients had brain metastases. No intraoperative, postoperative, or perioperative decline in pulmonary or neurologic function was observed.
The patient with metastatic lesions can also have other organ systems affected by the disease process. Liver metastases can alter coagulation and fibrinolytic mechanisms by damaging the necessary hepatic synthetic capabilities. Reamed nailing has been shown to potentially further alter these mechanisms [17]. Other authors have found that reaming has a stimulatory effect on the immune system, with the production of inflammatory cytokines that can have a beneficial or deleterious effect on overall outcomes [18-21]. In an animal model, the RIA has been shown to reduce fat emboli and associated systemic imbalances that are harmful after polytrauma [22]. This work, although performed in the trauma setting, could also have an impact on the cancer patient with systemic abnormalities.
The average estimated blood loss and operative times in our small series compare favorably with the previously reported values, ranging from 280-500 ml and 98-125 min in the literature. Our low rate of intraoperative complications is favorable when compared with previously reported rates as high as 45%. The overall average survival of 10.1 months is consistent with this patient population, with more aggressive tissue diagnoses associated with shorter survival time.
Limitations of this study include its retrospective nature and small sample size. Despite the fact that pulmonary complications following reamed intramedullary nailing are well documented in the trauma literature, there are no proven benefits in the literature that tumor debulking will decrease the rate of tumor and fat emboli during the treatment of pathologic fractures. Further development is needed in this area. The benefits of using the RIA could be more adequately documented with the addition of a control group. Furthermore, volumetric analysis of the preoperative images compared to the aspiration retrieved during the time of surgery would provide a better understanding of the efficacy of tumor debulking using the RIA.
Impending pathologic femur fractures are common sequelae of metastatic carcinoma and multiple myeloma. Reamed intramedullary stabilization is an advantageous treatment method to reduce pain and improve ambulatory status. Although relatively safe and common to most treating orthopaedists, complications do exist and must be planned for. In our small series, use of the RIA as an adjuvant therapy appears to be safe and beneficial for potentially reducing pulmonary and neurologic complications. The impending pathologic lesion could present an ideal area of application to further minimize risks in an already compromised patient population. REFERENCES
[1] Landis SH, Murray T, Bolden S, Wingo PA. Cancer statistics, 1998. CA Cancer J Clin. 1998;48:6-29.
[2] Harrington KD. The management of malignant pathologic fractures. Instr Course Lect. 1977;26:147-62.
[3] Sarahrudi K, Greitbauer M. Platzer P, Hausmann JT, Heinz T, Vécsei V. Surgical treatment of metastatic fractures of the femur: a retrospective analysis of 142 patients. J Trauma. 2009;66(4):1158-63.
[4] Nilsson J, Gustafon P. Surgery for metastatic lesions of the femur: good outcome after 245 operations in 216 patients. Injury. 2008;39(4):404-10.
[5] Yazawa Y, Frassica FJ, Chao EY, Pritchard DJ, Sim FH, Shives TC. Metastatic bone disease. A study of the surgical treatment of 166 pathologic humeral and femoral fractures. Clin Orthop. 1990;251:213-9.
[6] Issack PS, Barker J, Baker M, Kotwal SY, Lane JM. Surgical management of metastatic disease of the proximal part of the femur. J Bone Joint Surg Am. 2014;96A:2091-8.
[7] Piccioli A, Rossi B, Scaramuzzo L, Spinelli MS, Yang Z, Maccauro G. Intramedullary nailing for treatment of pathologic femoral fractures due to metastases. Injury. 2014;45: 412-7.
[8] Arvinius C, Parra JL, Mateo LS, Maroto RG, Borrego AF, Stern LL. Benefits of early intramedullary nailing in femoral metastases. Int Orthop. 2014;38:129-32.
[9] Peter RE, Schopfer A, Le Coultre B, Hoffmeyer P. Fat embolism and death during prophylactic osteosynthesis of a metastatic femur using an unreamed femoral nail. J Orthop Trauma. 1997;11(3):233-4.
[10] Gray AC, Torrens L, White TO, Carson A, Robinson CM. The cognitive effects of fat embolus syndrome following an isolated femoral shaft fracture. J Bone Joint Surg Am. 2007;89:1092-6.
[11] Kontakis GM, Tossounidis T, Weiss K, Pape HC, Giannoudis PV. Fat embolism: special situations bilateral femoral fractures and pathologic femoral fractures. Injury. 2006;37 Suppl 4:S19-24.
[12] Mirels H. Metastatic disease in long bones: a proposed scoring system for diagnosing impending pathologic fractures. Clin Orthop. 1989;249:256-64.
[13] Dalgorf D, Borkhoff CM, Stephen DJ, Finkelstein J, Kreder HJ. Venting during prophylactic nailing for femoral metastases: current orthopedic practice. Can J Surg. 2003;46:427-31.
[14] Roth SE, Rebello MM, Kreder H, Whyne CM. Pressurization of the metastatic femur during prophylactic intramedullary nail fixation. J Trauma. 2004;57(2):333-9.
[15] McHale S, Yariagadda R. A simple technique to improve venting the femur. Ann R Coll Surg Engl. 2014;96:311-2.
[16] Husebye EE, Lyberg T, Opdahl H, Laurvik H, Røise O. Cardiopulmonary response to reamed intramedullary nailing of the femur comparing traditional reaming with a one-step RIA reaming system: an experimental study in pigs. J Trauma. 2010;69(4):E6-14.
[17] Husebye EE, Lyberg T, Madsen JE, Eriksen M, Røise O. The influence of one step reamer-irrigator-aspirator technique on the intramedullary pressure in the pig femur. Injury. 2006;37(10):935-40.
[18] Robinson CM, Ludlam CA, Ray DC, Swann DG, Christie J. The coagulative and cardiorespiratory responses to reamed intramedullary nailing of isolated fractures. J Bone Joint Surg Br. 2001;83:963-73.
[19] Giannoudis PV, Smith RM, Bellamy MC, Morrison JF, Dickson RA, Guillou PJ.. Stimulation of inflammatory system by reamed and unreamed nailing of femoral fractures. J Bone Joint Surg Br. 1999;81B:356-61.
[20] Morley JR, Smith RM, Pape HC, MacDonald DA, Trejdosiewitz LK, Giannoudis PV. Stimulation of the local femoral inflammatory response to fracture and intramedullary reaming: a preliminary study of the source of the second hit phenomenon. J Bone Joint Surg Br. 2008;90B:393-9.
[21] Giannoudis PV, Harwood PJ, Loughenbury P, Van Griensven M, Krettek C, Pape HC. Correlation between IL-6 levels and the systemic inflammatory response score: can an IL-6 cutoff predict a SIRS state? J Trauma. 2008;65:646-52.
[22] Pape HC, Zelle BA, Hildebrand F, Giannoudis PV, Krettek C, van Griensven M. Reamed femoral nailing in sheep: does irrigation and aspiration of intramedullary contents alter the systemic response? J Bone Joint Surg Am. 2005;87A:2515-22.
Between April 2007 and May 2009, we used this technique on 8 patients with impending pathologic femur fracture. There were 7 females and 1 male with a mean age of 61.5 years (range 34-74 years). The pathology consisted of one colon, one breast, one renal cell, one squamous cell, and two non-small cell lung carcinomas and two cases of multiple myeloma. The lesion locations included 3 subtrochanteric, 2 diaphyseal, 1 distal third, and 2 entire femoral shaft. Seven of the lesions were lytic, and 1 mixed. All patients presented with rest pain and the average Mirels score was 11 (range 10-12). ASA classification was evenly divided, with 4 patients assigned class 3 and 4 patients given class 4 preoperatively. Pulmonary metastases were present in 6 patients, and brain metastases were present in 5 patients.
Operative time averaged 62.3 minutes (range 31-133 minutes). The estimated blood loss averaged 212.5 ml (range 100-600 ml). Implant diameters ranged from 11-14 mm with RIA diameters ranging from 12-15 mm. No intraoperative complications occurred. Postoperatively, hospital length of stay averaged 9.1 days (range 2-24 days), with discharge disposition to rehabilitation in 3 patients, home in 4, and skilled nursing facility in 1 patient. Perioperative (30-day) complications included chemotherapy reaction, ileus, vaginal bleeding, and thrombocytopenia. No patients had a decline in pulmonary or neurologic status in the perioperative period. Seven patients were allowed full weight bearing immediately postoperatively with assistive devices; the remaining patient was kept partial weight bearing secondary to extensive femoral involvement by 11 separate lesions. Pain relief by visual analog scale averaged 9 preoperatively and was decreased to 2 postoperatively. The patients were followed up for a mean of 24.2 months (range 13-37 months). No implant failures had occurred at most recent follow-up. Overall survival averaged 10.1 months (range 2-23 months). Three patients are currently living with 19.3 months average follow-up, with 5 patients having since died with 4.6 months average follow-up. DISCUSSION
Closed, reamed intramedullary fixation for impending pathologic femur fractures is a powerful tool for achieving immediate stability; however, some important potential concerns exist. The first is the limited amount of tumor debulking that can be accomplished with standard reaming. The RIA technique provides simultaneous reaming, irrigation, and aspiration, which probably provides more tumor removal than standard reaming. More traditional open approaches with curettage and cement augmentation provide the most extensive debulking. However, open curettage requires a more extensive approach, which probably increases the risks of infection, blood loss, and operative time. Admittedly, the exact amount of tumor debulking is not known; however, in this limited series, no implant failures related to local tumor recurrence were noted, compared with reported rates of up to 21%. All patients had radiotherapy postoperatively to the entire femoral field.
Another concern is the potential pulmonary and neurologic dysfunction that can result from reamed instrumentation of the femoral canal. This can in particular be true for patients with preoperative pulmonary compromise of function from metastatic disease. Fat embolism syndrome is typically characterized by mental confusion, hypoxia, and a petechial rash. Previous authors have shown that patients with pathologic femur fractures are at a higher risk for the development of this condition [8]. Other authors have examined venting the canal during intramedullary reaming but the significance in the oncologic population has yet to be elucidated [12-14]. Use of the RIA in animal models has demonstrated lower numbers of pulmonary emboli and lower intramedullary pressures when compared with traditional reaming [15,16]. In our small series, 6 patients had pulmonary metastases and compromised lung function, while 5 patients had brain metastases. No intraoperative, postoperative, or perioperative decline in pulmonary or neurologic function was observed.
The patient with metastatic lesions can also have other organ systems affected by the disease process. Liver metastases can alter coagulation and fibrinolytic mechanisms by damaging the necessary hepatic synthetic capabilities. Reamed nailing has been shown to potentially further alter these mechanisms [17]. Other authors have found that reaming has a stimulatory effect on the immune system, with the production of inflammatory cytokines that can have a beneficial or deleterious effect on overall outcomes [18-21]. In an animal model, the RIA has been shown to reduce fat emboli and associated systemic imbalances that are harmful after polytrauma [22]. This work, although performed in the trauma setting, could also have an impact on the cancer patient with systemic abnormalities.
The average estimated blood loss and operative times in our small series compare favorably with the previously reported values, ranging from 280-500 ml and 98-125 min in the literature. Our low rate of intraoperative complications is favorable when compared with previously reported rates as high as 45%. The overall average survival of 10.1 months is consistent with this patient population, with more aggressive tissue diagnoses associated with shorter survival time.
Limitations of this study include its retrospective nature and small sample size. Despite the fact that pulmonary complications following reamed intramedullary nailing are well documented in the trauma literature, there are no proven benefits in the literature that tumor debulking will decrease the rate of tumor and fat emboli during the treatment of pathologic fractures. Further development is needed in this area. The benefits of using the RIA could be more adequately documented with the addition of a control group. Furthermore, volumetric analysis of the preoperative images compared to the aspiration retrieved during the time of surgery would provide a better understanding of the efficacy of tumor debulking using the RIA.
Impending pathologic femur fractures are common sequelae of metastatic carcinoma and multiple myeloma. Reamed intramedullary stabilization is an advantageous treatment method to reduce pain and improve ambulatory status. Although relatively safe and common to most treating orthopaedists, complications do exist and must be planned for. In our small series, use of the RIA as an adjuvant therapy appears to be safe and beneficial for potentially reducing pulmonary and neurologic complications. The impending pathologic lesion could present an ideal area of application to further minimize risks in an already compromised patient population. REFERENCES
[1] Landis SH, Murray T, Bolden S, Wingo PA. Cancer statistics, 1998. CA Cancer J Clin. 1998;48:6-29.
[2] Harrington KD. The management of malignant pathologic fractures. Instr Course Lect. 1977;26:147-62.
[3] Sarahrudi K, Greitbauer M. Platzer P, Hausmann JT, Heinz T, Vécsei V. Surgical treatment of metastatic fractures of the femur: a retrospective analysis of 142 patients. J Trauma. 2009;66(4):1158-63.
[4] Nilsson J, Gustafon P. Surgery for metastatic lesions of the femur: good outcome after 245 operations in 216 patients. Injury. 2008;39(4):404-10.
[5] Yazawa Y, Frassica FJ, Chao EY, Pritchard DJ, Sim FH, Shives TC. Metastatic bone disease. A study of the surgical treatment of 166 pathologic humeral and femoral fractures. Clin Orthop. 1990;251:213-9.
[6] Issack PS, Barker J, Baker M, Kotwal SY, Lane JM. Surgical management of metastatic disease of the proximal part of the femur. J Bone Joint Surg Am. 2014;96A:2091-8.
[7] Piccioli A, Rossi B, Scaramuzzo L, Spinelli MS, Yang Z, Maccauro G. Intramedullary nailing for treatment of pathologic femoral fractures due to metastases. Injury. 2014;45: 412-7.
[8] Arvinius C, Parra JL, Mateo LS, Maroto RG, Borrego AF, Stern LL. Benefits of early intramedullary nailing in femoral metastases. Int Orthop. 2014;38:129-32.
[9] Peter RE, Schopfer A, Le Coultre B, Hoffmeyer P. Fat embolism and death during prophylactic osteosynthesis of a metastatic femur using an unreamed femoral nail. J Orthop Trauma. 1997;11(3):233-4.
[10] Gray AC, Torrens L, White TO, Carson A, Robinson CM. The cognitive effects of fat embolus syndrome following an isolated femoral shaft fracture. J Bone Joint Surg Am. 2007;89:1092-6.
[11] Kontakis GM, Tossounidis T, Weiss K, Pape HC, Giannoudis PV. Fat embolism: special situations bilateral femoral fractures and pathologic femoral fractures. Injury. 2006;37 Suppl 4:S19-24.
[12] Mirels H. Metastatic disease in long bones: a proposed scoring system for diagnosing impending pathologic fractures. Clin Orthop. 1989;249:256-64.
[13] Dalgorf D, Borkhoff CM, Stephen DJ, Finkelstein J, Kreder HJ. Venting during prophylactic nailing for femoral metastases: current orthopedic practice. Can J Surg. 2003;46:427-31.
[14] Roth SE, Rebello MM, Kreder H, Whyne CM. Pressurization of the metastatic femur during prophylactic intramedullary nail fixation. J Trauma. 2004;57(2):333-9.
[15] McHale S, Yariagadda R. A simple technique to improve venting the femur. Ann R Coll Surg Engl. 2014;96:311-2.
[16] Husebye EE, Lyberg T, Opdahl H, Laurvik H, Røise O. Cardiopulmonary response to reamed intramedullary nailing of the femur comparing traditional reaming with a one-step RIA reaming system: an experimental study in pigs. J Trauma. 2010;69(4):E6-14.
[17] Husebye EE, Lyberg T, Madsen JE, Eriksen M, Røise O. The influence of one step reamer-irrigator-aspirator technique on the intramedullary pressure in the pig femur. Injury. 2006;37(10):935-40.
[18] Robinson CM, Ludlam CA, Ray DC, Swann DG, Christie J. The coagulative and cardiorespiratory responses to reamed intramedullary nailing of isolated fractures. J Bone Joint Surg Br. 2001;83:963-73.
[19] Giannoudis PV, Smith RM, Bellamy MC, Morrison JF, Dickson RA, Guillou PJ.. Stimulation of inflammatory system by reamed and unreamed nailing of femoral fractures. J Bone Joint Surg Br. 1999;81B:356-61.
[20] Morley JR, Smith RM, Pape HC, MacDonald DA, Trejdosiewitz LK, Giannoudis PV. Stimulation of the local femoral inflammatory response to fracture and intramedullary reaming: a preliminary study of the source of the second hit phenomenon. J Bone Joint Surg Br. 2008;90B:393-9.
[21] Giannoudis PV, Harwood PJ, Loughenbury P, Van Griensven M, Krettek C, Pape HC. Correlation between IL-6 levels and the systemic inflammatory response score: can an IL-6 cutoff predict a SIRS state? J Trauma. 2008;65:646-52.
[22] Pape HC, Zelle BA, Hildebrand F, Giannoudis PV, Krettek C, van Griensven M. Reamed femoral nailing in sheep: does irrigation and aspiration of intramedullary contents alter the systemic response? J Bone Joint Surg Am. 2005;87A:2515-22.