- Email: [email protected]
Management of a parturient with high-grade osteosarcoma of the proximal femur: a multidisciplinary approach
340
Osteosarcoma in pregnancy
Management of a parturient with high-grade osteosarcoma of the proximal femur: a multidisciplinary approach A.A. Quaye,a K.A. Raskin,b J.L. Ecker,c L.R. Lefferta a b c
Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston, USA Department of Orthopedic Surgery, Massachusetts General Hospital, Boston, USA Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, USA
ABSTRACT Osteosarcoma is the most common primary malignant bone tumor, yet it is exceedingly rare in pregnancy. We present a case of a 33-year-old multiparous woman diagnosed with high-grade osteosarcoma during the third trimester of pregnancy. A plan was formulated to perform cesarean delivery at 33 weeks of gestation under spinal anesthesia, and, in subsequent surgery, radical femoral neck resection with limb salvage and adjuvant chemotherapy. The outcome was a healthy newborn baby boy and a diseasefree mother. This case highlights the benefits of multidisciplinary planning: balancing the needs of the developing fetus with those of the mother, mitigating the risk of pathologic fracture and ensuring timely oncologic therapy. c 2010 Elsevier Ltd. All rights reserved.
Keywords: Osteosarcoma; Pregnancy; Neuraxial anesthesia; Spinal; Epidural
Introduction Osteosarcoma is a proliferative high-grade bone tumor that usually affects children and the adolescent growing skeleton; it is rarely found during pregnancy.1 Three decades ago, amputation was the sole treatment for osteosarcoma and the five-year survival rate was less than 20% due to distant metastatic disease.2–4 With the introduction of early resection and adjuvant chemotherapy, 60–80% of patients with localized disease can be treated with limb salvage surgery and are long-term survivors.2,5,6 Management of the pregnant patient diagnosed with osteosarcoma can be complex given the potential for fetal harm from early oncologic intervention and the risk of pathologic fracture at delivery with associated micro-metastatic disease. We present a woman diagnosed with osteosarcoma of the proximal femur during the third trimester of pregnancy. A multidisciplinary approach was used to determine optimal management for both mother and child.
Case report A 33-year-old previously healthy woman (G3P2) presented to her outpatient obstetric clinic at 16 weeks of gestation with new onset low-back pain. She was diagnosed with sciatica of pregnancy and was managed supportively with physical therapy, chiropractic care, and Accepted March 2010 Correspondence to: A.A. Quaye, Department of Anesthesia and Critical Care, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114-2622, USA. E-mail address: [email protected]
anti-inflammatory agents. As pregnancy progressed, her symptoms worsened; by the third trimester, she had severe left leg pain and could not tolerate weight bearing. Magnetic Resonance Imaging (MRI) of the spine revealed lumbar scoliosis but nothing to explain these symptoms. A subsequent X-ray of the left hip revealed a lytic, destructive lesion measuring 4.5 · 5 cm centered in the left proximal femoral neck contiguously involving the intertrochanteric region and proximal femoral shaft (Fig. 1). She was admitted to an inpatient facility and further characterization by MRI revealed soft tissue breakthrough in the lateral cortex of the femoral neck with significant destruction of cortical bone. There was no acute fracture or joint dislocation (Fig. 2). At 33 weeks she was immediately referred to our orthopedic oncology department and transferred to our institution for further management. A non-contrast CT-guided needle biopsy was performed with lead shielding for fetal protection and subsequent histology revealed malignant spindle tumor cells consistent with high-grade osteosarcoma. We convened a multidisciplinary team comprised of oncologic orthopedists, high-risk obstetricians, obstetric anesthesiologists, neonatologists and nurses to discuss the optimal care of mother and fetus. The patient received a course of betamethasone therapy to optimize fetal lung maturity and immediate delivery was planned in order to expedite oncologic treatment. Due to the high risk of pathological fracture and its potential to compromise limb-salvage, we proceeded with cesarean delivery under neuraxial anesthesia with positioning assistance from the orthopedic team. We decided to delay limb salvage until after delivery to allow the uterine incision to epithelialize, decreasing the risk of wound
A.A. Quaye et al.
Fig. 1 X-ray of left pelvis-destructive lesion measuring 4.5 · 5 cm centered in the left proximal femoral neck involving the intertrochanteric region and proximal femoral shaft.
341 cant discomfort and was immediately readjusted to a semi-seated position. Despite the visible lumbar scoliosis, the subarachnoid space was easily attained with a 25-gauge Whitacre needle and 1.6 mL hyperbaric 0.75% bupivacaine, 15 lg fentanyl and 0.2 mg preservative free morphine were injected intrathecally. The patient was then carefully rotated to the supine position with left uterine displacement. A T4 sensory level was confirmed and a healthy 2600 g male infant, with Apgar scores of 8 and 9 at 1 and 5 min respectively, was delivered. Upon completion of surgery, the patient’s hip was again manually immobilized as she was transferred to the stretcher. At regular intervals during her recovery, she was evaluated by the orthopedic team who concluded that there was no evidence of fracture or dislocation at the acetabular joint. Two days after delivery, she underwent successful radical resection of the left proximal femur and endoprosthetic bipolar hemiarthroplasty reconstruction. Wound margins were clear of sarcoma. Subsequently, she completed a course of high-dose doxorubicin and cisplatin neoadjuvant chemotherapy and is currently disease free.
Discussion contamination with sarcoma cells if sarcoma positive margins were encountered. The orthopedic team was present to manage patient positioning before, during, and after cesarean delivery. The patient’s hip joint was manually immobilized as she was moved to the right lateral decubitus position for spinal placement. However, she experienced signifi-
Fig. 2 Sagittal MRI of the femoral neck-lytic lesion associated with soft tissue breakthrough of the lateral cortex and destruction of cortical bone.
We present the peripartum management of a parturient with high-grade osteosarcoma of the proximal femur. The occurrence of osteosarcoma in pregnant women is uncommon and the influence of pregnancy on the proliferation of these tumors remains unclear.1 It has been postulated that the hormonal changes which occur during pregnancy can contribute to the growth and recurrence of sarcomas in susceptible individuals; however, there is no clear evidence that pregnancy adversely affects the course of the disease.7 Although sarcomas rarely develop during pregnancy, musculoskeletal pain, especially involving the lower back and pelvic structures, is a common occurrence.8 In most instances, musculoskeletal pain is caused by the gravid uterus exerting mechanical stress on the spine and pelvis along with increased hormonal levels that cause ligamentous laxity and fluid retention.9 Most often, the pain which develops is transient and can be treated conservatively. Unfortunately, due to the high frequency of musculoskeletal pain during pregnancy, diagnosis of rare yet serious conditions including lumbar disc herniation, osteonecrosis and osteogenic sarcomas, can be delayed. It is recommended that if a patient develops radicular pain, or if symptoms worsen despite supportive treatment, more serious etiologies for pain should be investigated as immediate and invasive intervention may be required. MRI is the imaging modality of choice for distinguishing these conditions.9 When the diagnosis of osteosarcoma was made, the decision was made to proceed with cesarean delivery, as
342
Maternal death from ESBL producing E. coli
the size and position of the lesion posed a challenge for labor and vaginal birth. Specifically, any force applied across the joint from flexion, abduction and external rotation put the hip at risk of fracture. It has been reported that pathologic fracture confers an increased risk of local recurrence and decreased rate of survival when compared with patients who have not sustained fracture.10 These considerations influenced our anesthetic approach. Neither general nor neuraxial anesthesia provides a guarantee of perioperative hip stabilization. With general anesthesia, there is a risk of uncontrolled hip movements upon induction before the onset of neuromuscular blockade, and upon emergence, even in the setting of deep extubation. Conversely, neuraxial anesthesia requires repositioning of the patient before, during, and after placement, albeit potentially more controlled, which could cause fracture. Since neither method could be guaranteed to prevent pathologic fracture, we elected for a neuraxial anesthetic, as it is the preferred technique for elective cesarean delivery unless contraindicated.11 Whilst an epidural would have provided a vehicle for both intra- and postoperative pain management, we elected for a spinal anesthetic given the need to monitor lower extremity neurological signs postoperatively. Ideally, pregnancy should not delay oncologic treatment for bone and soft tissue sarcomas as early treatment is necessary to provide the most favorable maternal outcomes.12 It is estimated that 60–80% of patients with localized sarcoma remain cancer free following early resection and neoadjuvant chemotherapy.2,5,6 As our patient was in her third trimester when diagnosed with osteosarcoma, the decision for cesarean delivery before term in order to expedite oncologic treatment posed few risks to both mother and fetus. However, for women diagnosed with malignancies earlier in pregnancy, the decision of when to treat can be more challenging as oncologic treatment in the antepartum period can potentially lead to devastating fetal consequences. There are published reports of patients diagnosed with localized musculoskeletal tumors during pregnancy who underwent surgical treatment and/or chemotherapy before delivery without adversely impacting the fetus.12,13 Ultimately, the decision of when to pursue oncologic treatment should be made on a case by case basis with careful interdisciplinary planning balancing maternal and fetal risks.
0959-289X/$ - see front matter c 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.ijoa.2010.03.013
There are no published guidelines for the peripartum management of patients diagnosed with osteosarcoma. As such, it is ideal for a multidisciplinary team comprised of oncologic surgeons, obstetricians, obstetric anesthesiologists, neonatologists and nurses to work together to develop a care plan based on factors including the fetal gestational age, the anatomic site and grade of the lesion, and additional maternal comorbidities.
References 1. Merimsky O, Le Cesne A. Soft tissue and bone sarcomas in association with pregnancy. Acta Oncol 1998;37:721–7. 2. Wittig JC, Bickels J, Priebat D, et al. Osteosarcoma: a multidisciplinary approach to diagnosis and treatment. Am Fam Physician 2002;65:1123–32. 3. Marcove RC, Mike´ V, Hajek JV, Levin AG, Hutter RV. Osteogenic sarcoma under the age of twenty-one. A review of one hundred and forty-five operative cases. J Bone Joint Surg Am 1970;52:411–23. 4. Gaffney R, Unni KK, Sim FH, Slezak JM, Esther RJ, Bolander ME. Follow-up study of long-term survivors of osteosarcoma in the pre-chemotherapy era. Hum Pathol 2006;37:1009–14. 5. Fuchs N, Bielack SS, Epler D, et al. Long term results of the cooperative German–Australian–Swiss osteosarcoma study group’s protocol COSS-86 of intensive multidrug chemotherapy and surgery for osteosarcoma of the limbs. Ann Oncol 1998;9:893–9. 6. Ferrari S, Palmerini E. Adjuvant and neoadjuvant combination chemotherapy for osteogenic sarcoma. Curr Opin Oncol 2007;19:341–6. 7. Merimsky O, Inbar M, Issakov J, et al. Gestation-related malignant musculoskeletal tumors. Isr Med Assoc J 2003;5:264–7. 8. Ritchie J. Orthopedic considerations during pregnancy. Clin Obstet Gynecol 2003;46:456–66. 9. Smith MW, Marcus PS, Wurtz LD. Orthopedic issues in pregnancy. Obstet Gynecol Surv 2008;63:103–11. 10. Scully SP, Ghert MA, Zurakowski D, Thompson RC, Gebhardt MC. Pathologic fracture in osteosarcoma: prognostic importance and treatment implications. J Bone Joint Surg Am 2002;84:49–57. 11. Tsen L. Anesthesia for caesarean delivery. In: Chestnut DH, Polley LS, Tsen LC, Wong CA, editors. Obstetric Anesthesia Principles and Practice. 4th ed. Philadelphia: Elsevier Mosby; 2009. p. 521–73. 12. Maxwell C, Barzilay B, Shah V, Wunder JS, Bell R, Farine D. Maternal and neonatal outcomes in pregnancies complicated by bone and soft-tissue tumors. Obstet Gynecol 2004;104:344–8. 13. Nakajima W, Ishida A, Takahashi M, et al. Good outcome for infant of mother treated with chemotherapy for ewing sarcoma at 25 to 30 weeks’ gestation. J Pediatr Hematol Oncol 2004;26: 308–11.
Osteosarcoma in pregnancy
Management of a parturient with high-grade osteosarcoma of the proximal femur: a multidisciplinary approach A.A. Quaye,a K.A. Raskin,b J.L. Ecker,c L.R. Lefferta a b c
Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston, USA Department of Orthopedic Surgery, Massachusetts General Hospital, Boston, USA Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, USA
ABSTRACT Osteosarcoma is the most common primary malignant bone tumor, yet it is exceedingly rare in pregnancy. We present a case of a 33-year-old multiparous woman diagnosed with high-grade osteosarcoma during the third trimester of pregnancy. A plan was formulated to perform cesarean delivery at 33 weeks of gestation under spinal anesthesia, and, in subsequent surgery, radical femoral neck resection with limb salvage and adjuvant chemotherapy. The outcome was a healthy newborn baby boy and a diseasefree mother. This case highlights the benefits of multidisciplinary planning: balancing the needs of the developing fetus with those of the mother, mitigating the risk of pathologic fracture and ensuring timely oncologic therapy. c 2010 Elsevier Ltd. All rights reserved.
Keywords: Osteosarcoma; Pregnancy; Neuraxial anesthesia; Spinal; Epidural
Introduction Osteosarcoma is a proliferative high-grade bone tumor that usually affects children and the adolescent growing skeleton; it is rarely found during pregnancy.1 Three decades ago, amputation was the sole treatment for osteosarcoma and the five-year survival rate was less than 20% due to distant metastatic disease.2–4 With the introduction of early resection and adjuvant chemotherapy, 60–80% of patients with localized disease can be treated with limb salvage surgery and are long-term survivors.2,5,6 Management of the pregnant patient diagnosed with osteosarcoma can be complex given the potential for fetal harm from early oncologic intervention and the risk of pathologic fracture at delivery with associated micro-metastatic disease. We present a woman diagnosed with osteosarcoma of the proximal femur during the third trimester of pregnancy. A multidisciplinary approach was used to determine optimal management for both mother and child.
Case report A 33-year-old previously healthy woman (G3P2) presented to her outpatient obstetric clinic at 16 weeks of gestation with new onset low-back pain. She was diagnosed with sciatica of pregnancy and was managed supportively with physical therapy, chiropractic care, and Accepted March 2010 Correspondence to: A.A. Quaye, Department of Anesthesia and Critical Care, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114-2622, USA. E-mail address: [email protected]
anti-inflammatory agents. As pregnancy progressed, her symptoms worsened; by the third trimester, she had severe left leg pain and could not tolerate weight bearing. Magnetic Resonance Imaging (MRI) of the spine revealed lumbar scoliosis but nothing to explain these symptoms. A subsequent X-ray of the left hip revealed a lytic, destructive lesion measuring 4.5 · 5 cm centered in the left proximal femoral neck contiguously involving the intertrochanteric region and proximal femoral shaft (Fig. 1). She was admitted to an inpatient facility and further characterization by MRI revealed soft tissue breakthrough in the lateral cortex of the femoral neck with significant destruction of cortical bone. There was no acute fracture or joint dislocation (Fig. 2). At 33 weeks she was immediately referred to our orthopedic oncology department and transferred to our institution for further management. A non-contrast CT-guided needle biopsy was performed with lead shielding for fetal protection and subsequent histology revealed malignant spindle tumor cells consistent with high-grade osteosarcoma. We convened a multidisciplinary team comprised of oncologic orthopedists, high-risk obstetricians, obstetric anesthesiologists, neonatologists and nurses to discuss the optimal care of mother and fetus. The patient received a course of betamethasone therapy to optimize fetal lung maturity and immediate delivery was planned in order to expedite oncologic treatment. Due to the high risk of pathological fracture and its potential to compromise limb-salvage, we proceeded with cesarean delivery under neuraxial anesthesia with positioning assistance from the orthopedic team. We decided to delay limb salvage until after delivery to allow the uterine incision to epithelialize, decreasing the risk of wound
A.A. Quaye et al.
Fig. 1 X-ray of left pelvis-destructive lesion measuring 4.5 · 5 cm centered in the left proximal femoral neck involving the intertrochanteric region and proximal femoral shaft.
341 cant discomfort and was immediately readjusted to a semi-seated position. Despite the visible lumbar scoliosis, the subarachnoid space was easily attained with a 25-gauge Whitacre needle and 1.6 mL hyperbaric 0.75% bupivacaine, 15 lg fentanyl and 0.2 mg preservative free morphine were injected intrathecally. The patient was then carefully rotated to the supine position with left uterine displacement. A T4 sensory level was confirmed and a healthy 2600 g male infant, with Apgar scores of 8 and 9 at 1 and 5 min respectively, was delivered. Upon completion of surgery, the patient’s hip was again manually immobilized as she was transferred to the stretcher. At regular intervals during her recovery, she was evaluated by the orthopedic team who concluded that there was no evidence of fracture or dislocation at the acetabular joint. Two days after delivery, she underwent successful radical resection of the left proximal femur and endoprosthetic bipolar hemiarthroplasty reconstruction. Wound margins were clear of sarcoma. Subsequently, she completed a course of high-dose doxorubicin and cisplatin neoadjuvant chemotherapy and is currently disease free.
Discussion contamination with sarcoma cells if sarcoma positive margins were encountered. The orthopedic team was present to manage patient positioning before, during, and after cesarean delivery. The patient’s hip joint was manually immobilized as she was moved to the right lateral decubitus position for spinal placement. However, she experienced signifi-
Fig. 2 Sagittal MRI of the femoral neck-lytic lesion associated with soft tissue breakthrough of the lateral cortex and destruction of cortical bone.
We present the peripartum management of a parturient with high-grade osteosarcoma of the proximal femur. The occurrence of osteosarcoma in pregnant women is uncommon and the influence of pregnancy on the proliferation of these tumors remains unclear.1 It has been postulated that the hormonal changes which occur during pregnancy can contribute to the growth and recurrence of sarcomas in susceptible individuals; however, there is no clear evidence that pregnancy adversely affects the course of the disease.7 Although sarcomas rarely develop during pregnancy, musculoskeletal pain, especially involving the lower back and pelvic structures, is a common occurrence.8 In most instances, musculoskeletal pain is caused by the gravid uterus exerting mechanical stress on the spine and pelvis along with increased hormonal levels that cause ligamentous laxity and fluid retention.9 Most often, the pain which develops is transient and can be treated conservatively. Unfortunately, due to the high frequency of musculoskeletal pain during pregnancy, diagnosis of rare yet serious conditions including lumbar disc herniation, osteonecrosis and osteogenic sarcomas, can be delayed. It is recommended that if a patient develops radicular pain, or if symptoms worsen despite supportive treatment, more serious etiologies for pain should be investigated as immediate and invasive intervention may be required. MRI is the imaging modality of choice for distinguishing these conditions.9 When the diagnosis of osteosarcoma was made, the decision was made to proceed with cesarean delivery, as
342
Maternal death from ESBL producing E. coli
the size and position of the lesion posed a challenge for labor and vaginal birth. Specifically, any force applied across the joint from flexion, abduction and external rotation put the hip at risk of fracture. It has been reported that pathologic fracture confers an increased risk of local recurrence and decreased rate of survival when compared with patients who have not sustained fracture.10 These considerations influenced our anesthetic approach. Neither general nor neuraxial anesthesia provides a guarantee of perioperative hip stabilization. With general anesthesia, there is a risk of uncontrolled hip movements upon induction before the onset of neuromuscular blockade, and upon emergence, even in the setting of deep extubation. Conversely, neuraxial anesthesia requires repositioning of the patient before, during, and after placement, albeit potentially more controlled, which could cause fracture. Since neither method could be guaranteed to prevent pathologic fracture, we elected for a neuraxial anesthetic, as it is the preferred technique for elective cesarean delivery unless contraindicated.11 Whilst an epidural would have provided a vehicle for both intra- and postoperative pain management, we elected for a spinal anesthetic given the need to monitor lower extremity neurological signs postoperatively. Ideally, pregnancy should not delay oncologic treatment for bone and soft tissue sarcomas as early treatment is necessary to provide the most favorable maternal outcomes.12 It is estimated that 60–80% of patients with localized sarcoma remain cancer free following early resection and neoadjuvant chemotherapy.2,5,6 As our patient was in her third trimester when diagnosed with osteosarcoma, the decision for cesarean delivery before term in order to expedite oncologic treatment posed few risks to both mother and fetus. However, for women diagnosed with malignancies earlier in pregnancy, the decision of when to treat can be more challenging as oncologic treatment in the antepartum period can potentially lead to devastating fetal consequences. There are published reports of patients diagnosed with localized musculoskeletal tumors during pregnancy who underwent surgical treatment and/or chemotherapy before delivery without adversely impacting the fetus.12,13 Ultimately, the decision of when to pursue oncologic treatment should be made on a case by case basis with careful interdisciplinary planning balancing maternal and fetal risks.
0959-289X/$ - see front matter c 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.ijoa.2010.03.013
There are no published guidelines for the peripartum management of patients diagnosed with osteosarcoma. As such, it is ideal for a multidisciplinary team comprised of oncologic surgeons, obstetricians, obstetric anesthesiologists, neonatologists and nurses to work together to develop a care plan based on factors including the fetal gestational age, the anatomic site and grade of the lesion, and additional maternal comorbidities.
References 1. Merimsky O, Le Cesne A. Soft tissue and bone sarcomas in association with pregnancy. Acta Oncol 1998;37:721–7. 2. Wittig JC, Bickels J, Priebat D, et al. Osteosarcoma: a multidisciplinary approach to diagnosis and treatment. Am Fam Physician 2002;65:1123–32. 3. Marcove RC, Mike´ V, Hajek JV, Levin AG, Hutter RV. Osteogenic sarcoma under the age of twenty-one. A review of one hundred and forty-five operative cases. J Bone Joint Surg Am 1970;52:411–23. 4. Gaffney R, Unni KK, Sim FH, Slezak JM, Esther RJ, Bolander ME. Follow-up study of long-term survivors of osteosarcoma in the pre-chemotherapy era. Hum Pathol 2006;37:1009–14. 5. Fuchs N, Bielack SS, Epler D, et al. Long term results of the cooperative German–Australian–Swiss osteosarcoma study group’s protocol COSS-86 of intensive multidrug chemotherapy and surgery for osteosarcoma of the limbs. Ann Oncol 1998;9:893–9. 6. Ferrari S, Palmerini E. Adjuvant and neoadjuvant combination chemotherapy for osteogenic sarcoma. Curr Opin Oncol 2007;19:341–6. 7. Merimsky O, Inbar M, Issakov J, et al. Gestation-related malignant musculoskeletal tumors. Isr Med Assoc J 2003;5:264–7. 8. Ritchie J. Orthopedic considerations during pregnancy. Clin Obstet Gynecol 2003;46:456–66. 9. Smith MW, Marcus PS, Wurtz LD. Orthopedic issues in pregnancy. Obstet Gynecol Surv 2008;63:103–11. 10. Scully SP, Ghert MA, Zurakowski D, Thompson RC, Gebhardt MC. Pathologic fracture in osteosarcoma: prognostic importance and treatment implications. J Bone Joint Surg Am 2002;84:49–57. 11. Tsen L. Anesthesia for caesarean delivery. In: Chestnut DH, Polley LS, Tsen LC, Wong CA, editors. Obstetric Anesthesia Principles and Practice. 4th ed. Philadelphia: Elsevier Mosby; 2009. p. 521–73. 12. Maxwell C, Barzilay B, Shah V, Wunder JS, Bell R, Farine D. Maternal and neonatal outcomes in pregnancies complicated by bone and soft-tissue tumors. Obstet Gynecol 2004;104:344–8. 13. Nakajima W, Ishida A, Takahashi M, et al. Good outcome for infant of mother treated with chemotherapy for ewing sarcoma at 25 to 30 weeks’ gestation. J Pediatr Hematol Oncol 2004;26: 308–11.