漿細胞骨髓瘤相關骨質病變的診斷和外科治療策略
發(fā)布時間：2018-09-01 10:22
【摘要】：背景骨髓中單克隆漿細胞異常大量增殖并分泌單克隆免疫球蛋白造成的惡性腫瘤,稱為漿細胞骨髓瘤。在有些國家的血液系統(tǒng)惡性腫瘤中,漿細胞骨髓瘤的發(fā)病率可排在第二位,囊括多種類型,而又以多發(fā)性骨髓瘤(multiple myeloma, MM)最多見,可發(fā)生于全身各處的骨骼。另外,臨床上亦有僅累及單一病灶的孤立性骨髓瘤(solitary myeloma, SM,又稱為孤立性漿細胞瘤)。病變以中軸骨多見,首先侵犯松質骨,然后逐漸破壞皮質骨。MM發(fā)病率較高,約為0.7-3.3/100000,SM僅占所有骨髓瘤的2%,有文獻報道2/3的SM將最終進展為MM。而且漿細胞骨髓瘤的發(fā)病率隨著人口老齡化還在不斷增高。漿細胞骨髓瘤分泌的細胞因子會導致破骨細胞的活動加強及成骨細胞活動的減弱,進而引起骨吸收和骨形成失衡,最終導致骨痛、全身彌漫性骨質疏松和骨質破壞、高鈣血癥及其他骨的相關事件(病理性骨折、脊柱穩(wěn)定性喪失、脊髓和神經根受壓等)等。如果不給予有效的針對治療,大約50%的病人在疾病發(fā)展過程總會出現至少一種骨骼相關事件。病理性骨折等事件的發(fā)生將在很大程度上危及患者的生存質量和預期壽命,曾有研究發(fā)現出現病理性骨折的漿細胞骨髓瘤患者的死亡率比未出現病理性骨折的患者要高20%。目前對于漿細胞骨髓瘤患者手術治療的必要性,各種手術方式的適應癥,手術對患者生活質量及預后的作用還沒有確定的結論。有研究認為對漿細胞骨髓瘤進行手術治療能夠改善患者生存質量,也有研究認為孤立性漿細胞瘤的相關骨病變并不需要外科治療。目的通過搜集并探討在山東大學齊魯醫(yī)院骨科就診并接受手術治療的漿細胞骨髓瘤患者的臨床表現、診斷方法、外科治療指征、手術方式選擇及手術后患者的恢復情況,評估不同外科治療方法的安全性和必要性,系統(tǒng)地分析漿細胞骨髓瘤相關骨骼病變的外科綜合治療方案,為骨科醫(yī)生對骨髓瘤相關骨骼病變的治療提供參考,避免誤診、治療不足和過度。方法對2005年5月至2015年5月于山東大學齊魯醫(yī)院骨科就診并行手術治療的88名漿細胞骨髓瘤病人進行隨訪,并回顧性對既往收集到的資料進行分析。其中女性患者39例,男性患者49例,骨科首診年齡30～84歲(平均60.0歲)。以脊柱病變就診者78例,以下肢長骨病變就診者10例(股骨9例,脛骨1例)。最終確診多發(fā)者85例,單發(fā)者3例。其中51例為骨科確診,37例為其他科室漿細胞骨髓瘤確診后于本中心接受手術治療。病人就診的主要癥狀有頸、腰、背部或下肢疼痛,神經功能損害和病理性骨折。以脊柱病變就診者中,共有12例合并脊髓功能損害。5例按照Frankel分級可歸為B級,其他7例則為C級。這些患者都在本中心接受了外科手術治療。搜集記錄患者術前及術后2周、半年的Oswestry功能障礙評分(ODI)、Frankel分級、Kamofsky評分、視覺模擬評分(Visual Analogue Scale/Score)和Mirel評分等評價手術效果,其中對于VAS、ODI和Kamofsky評分,使用SPSS統(tǒng)計分析軟件進行配對t檢驗。對患者的恢復情況進行定期的隨訪和評估。結果患者手術后的隨訪時間最短6個月。20例病人共32個病變的椎體行經皮椎體成形術或者是椎體后凸成形術,共包括胸椎14個,腰椎18個。對于這批病人,術前VAS 4-8分,平均6.45±1.05分,術后兩周的評分是0-3分,平均為1.05±0.89,隨訪至術后半年計算VAS平均值為1.35±0.67；手術前所有患者Oswestry評分計算的平均值是68.1±8.74分,隨訪術后第二周的平均值降為15.0±8.17,至術后半年再次隨訪時則至17.1±7.50,這些差異經計算具有統(tǒng)計學意義(p0.01)。行開放手術的患者中,頸椎6例,胸椎37例,腰椎15例。其中49例患者行后路手術,47例為姑息性手術(單純椎管減壓椎弓根釘內固定術),其中又有11例同時行開放椎體成形術,剩余2例單發(fā)漿細胞骨髓瘤行后路全椎體分塊／整塊切除、鈦網骨水泥填充、椎弓根釘內固定術；5例行前路椎體次全切除,鈦網骨水泥植入,鋼／鈦板內固定術；4例為前后路聯(lián)合術。術前平均VAS 6.47±1.23,術后半年為1.32±0.71。術前平均Kamofsky評分39.82±8.48,手術半年后改善為77.76±9.74。這些術后改善在統(tǒng)計學上具有意義(p0.01)。而對于12例有明顯脊髓功能損害的患者中,9例患者的Frankel分級手術后半年改善為D級,3例患者改善為E級,根據患者自述疼痛比術前要好轉,肌力也有恢復。單發(fā)者接受術后局部疼痛等癥狀消失,截止隨訪結束未見復發(fā)。以股骨病變就診者9例,Mirel評分均大于9分。7例骨皮質完整者行腫瘤刮除、骨水泥填充、內固定術,2例病變位于股骨近端,1例患者接受人工股骨頭置換術,1例則接受全髖假體置換。術后隨訪時間17～47個月,平均隨訪時間31.75個月。隨訪期間患者,1例失訪,無二次手術,無死亡病例發(fā)生,功能恢復良好。其中以脛骨病變就診的患者1例,經詳細檢查確診為單發(fā)病變,行右脛骨骨髓瘤切除、定制假體置換,腓腸肌內側肌瓣轉移術。術后隨訪12個月,一般情況可,無復發(fā),無遠期并發(fā)癥。結論1、漿細胞骨骨髓瘤是一種血液系統(tǒng)疾病,最常見的受累部位是骨骼,可導致疼痛、病理骨折和脊髓神經功能損害等骨骼相關事件。部分病人到骨科就診并需要手術治療,此時,明確診斷、防治骨相關事件是骨科醫(yī)生的主要工作。2、漿細胞骨髓瘤骨質病變最常累及脊柱,四肢長骨相對少見。3、根據腫瘤累及部位、骨質破壞情況、脊髓神經損害程度、臨床表現及全身狀況選擇合適的手術干預方式。4、對脊柱漿細胞骨髓瘤,單純病理骨折或瀕臨骨折,尤其伴有疼痛的患者可進行經皮椎體成形術或經皮椎體后凸成形術治療,對于合并有脊髓神經損害者或脊柱明顯不穩(wěn)者,行椎管減壓和脊柱固定等開放手術十分必要。少數情況下行腫瘤切除術。5、對長骨骨髓瘤,骨折風險較高或已經發(fā)生病理性骨折者,鄰近關節(jié)端者可行假體置換術,位于骨干者可行內固定,骨水泥填充骨質缺損。6、針對多發(fā)性骨髓瘤的手術為姑息性手術,并不是以治愈骨髓瘤為目的,是作為一種輔助的治療方式。
[Abstract]:Background Malignant tumors caused by abnormal proliferation of monoclonal plasma cells and secretion of monoclonal immunoglobulin in bone marrow are called plasma cell myeloma. In addition, there are solitary myeloma (SM) with a single lesion. Most of the lesions are located in the medial axis bone, invading the cancellous bone first, and then gradually destroying the cortical bone. The incidence of MM is high, about 0.7-3.3/100000, and SM only accounts for all the myeloma. 2%. It has been reported that 2/3 of SM will eventually develop into MM. Moreover, the incidence of plasma cell myeloma is increasing with the aging of the population. Cytokines secreted by plasma cell myeloma will lead to increased activity of osteoclasts and decreased activity of osteoblasts, which will lead to bone resorption and bone formation imbalance, eventually leading to bone pain and systemic diffuse. Diffuse osteoporosis and bone destruction, hypercalcemia and other bone-related events (pathological fractures, loss of spinal stability, compression of the spinal cord and nerve roots, etc.). Without effective treatment, about 50% of patients will always have at least one bone-related event during the course of disease development. Pathological fractures and other events will occur. To a great extent, it endangers the quality of life and life expectancy of patients. Studies have found that the mortality rate of plasma cell myeloma patients with pathological fractures is 20% higher than that of patients without pathological fractures. The quality and prognosis of patients with plasmacytoma have not yet been determined. Some studies have suggested that surgical treatment of plasmacytoma can improve the quality of life of patients. Others have suggested that surgery is not necessary for osteopathy associated with solitary plasmacytoma. To evaluate the safety and necessity of different surgical treatments, to systematically analyze the comprehensive surgical treatment of plasma cell myeloma-related skeletal diseases, and to provide orthopaedics with a view to the treatment of myeloma. Methods From May 2005 to May 2015, 88 patients with plasmacytic myeloma who underwent surgery in the Department of Orthopedics of Qilu Hospital of Shandong University were followed up and analyzed retrospectively. Eighty-five patients were diagnosed as multiple and three as solitary. Of them, 51 were confirmed by orthopedics and 37 were treated by surgery in our center after the diagnosis of plasma cell myeloma in other departments. The main symptoms were pain in the neck, waist, back or lower limbs, neurological impairment, and pathological fractures. Of the patients with spinal lesions, 12 were associated with spinal cord dysfunction. Five were classified as grade B according to Frankel's classification, while the other seven were classified as grade C. All of the patients underwent surgical treatment at the center. Six-month Oswestry dysfunction score (ODI), Frankel score, Kamofsky score, Visual Analogue Scale/Score and Mirial score were used to evaluate the surgical outcomes. The VAS, ODI and Kamofsky scores were matched with paired t-test using SPSS statistical analysis software. The recovery of the patients was followed up and evaluated regularly. The shortest follow-up time was 6 months.20 patients with 32 lesions underwent percutaneous vertebroplasty or kyphoplasty, including 14 thoracic vertebrae and 18 lumbar vertebrae. The average VAS was 1.35 [0.67], the Oswestry score was 68.1 [8.74], the average value was 15.0 [8.17] at the second week of follow-up, and 17.1 [7.50] at the second half year of follow-up. These differences were statistically significant (p0.01). Among the patients undergoing open surgery, 6 had cervical vertebrae, 37 had thoracic vertebrae. 15 cases of lumbar spine were treated by posterior approach, 47 cases by palliative operation (simple spinal canal decompression and pedicle screw internal fixation), 11 cases by open vertebroplasty, the remaining 2 cases by single plasma cell myeloma posterior total vertebral body block / block resection, titanium mesh cement filling, pedicle screw internal fixation; 5 cases by anterior approach; Subtotal vertebrectomy, titanium mesh cement implantation, and steel/titanium plate internal fixation were performed in 4 patients. The average VAS was 6.47 (+ 1.23) before operation and 1.32 (+ 0.71) after operation. The average Kamofsky score was 39.82 (+ 8.48) before operation and 77.76 (+ 9.74) after operation. Among the patients with spinal cord dysfunction, Frankel's grade D was improved in 9 cases and E in 3 cases half a year after operation. According to the patient's self-report, the pain was better and the muscle strength was restored. Seven patients with complete cortex underwent tumor curettage, cementation and internal fixation, 2 lesions located in the proximal femur, 1 artificial femoral head replacement and 1 total hip prosthesis replacement. The follow-up period ranged from 17 to 47 months, with an average follow-up period of 31.75 months. One patient with tibial lesion was diagnosed as a single lesion by detailed examination. The right tibial myeloma was excised, the prosthesis was replaced, and the medial gastrocnemius muscle flap was transferred. The most common site of bone involvement is bone, which can lead to pain, pathological fractures and spinal cord nerve damage and other bone-related events. Some patients go to orthopedics and need surgery. At this time, definite diagnosis, prevention and treatment of bone-related events is the main work of orthopaedics. 2. Plasma cell myeloma osteopathy most often affects the spine, limbs. Long bones are relatively rare. 3. Appropriate surgical interventions are selected according to the site of tumor involvement, bone destruction, degree of spinal cord nerve damage, clinical manifestations and general condition. 4. Percutaneous vertebroplasty or percutaneous kyphoplasty can be performed in patients with spinal plasma cell myeloma, simple pathological fracture or near fracture, especially in patients with pain. Surgical treatment is necessary for patients with spinal cord nerve damage or spinal instability. In rare cases, tumor resection is necessary. 5. For long bone myeloma, the risk of fracture is high or pathological fracture has occurred, prosthesis replacement is feasible at the adjacent end of the joint, and for those located in the backbone. Internal fixation, bone cement filling bone defect. 6. Palliative surgery for multiple myeloma is not for the purpose of curing myeloma, but as an adjuvant treatment.
【學位授予單位】：山東大學
【學位級別】：碩士
【學位授予年份】：2016
【分類號】：R733.3
本文編號：2216902
[Abstract]:Background Malignant tumors caused by abnormal proliferation of monoclonal plasma cells and secretion of monoclonal immunoglobulin in bone marrow are called plasma cell myeloma. In addition, there are solitary myeloma (SM) with a single lesion. Most of the lesions are located in the medial axis bone, invading the cancellous bone first, and then gradually destroying the cortical bone. The incidence of MM is high, about 0.7-3.3/100000, and SM only accounts for all the myeloma. 2%. It has been reported that 2/3 of SM will eventually develop into MM. Moreover, the incidence of plasma cell myeloma is increasing with the aging of the population. Cytokines secreted by plasma cell myeloma will lead to increased activity of osteoclasts and decreased activity of osteoblasts, which will lead to bone resorption and bone formation imbalance, eventually leading to bone pain and systemic diffuse. Diffuse osteoporosis and bone destruction, hypercalcemia and other bone-related events (pathological fractures, loss of spinal stability, compression of the spinal cord and nerve roots, etc.). Without effective treatment, about 50% of patients will always have at least one bone-related event during the course of disease development. Pathological fractures and other events will occur. To a great extent, it endangers the quality of life and life expectancy of patients. Studies have found that the mortality rate of plasma cell myeloma patients with pathological fractures is 20% higher than that of patients without pathological fractures. The quality and prognosis of patients with plasmacytoma have not yet been determined. Some studies have suggested that surgical treatment of plasmacytoma can improve the quality of life of patients. Others have suggested that surgery is not necessary for osteopathy associated with solitary plasmacytoma. To evaluate the safety and necessity of different surgical treatments, to systematically analyze the comprehensive surgical treatment of plasma cell myeloma-related skeletal diseases, and to provide orthopaedics with a view to the treatment of myeloma. Methods From May 2005 to May 2015, 88 patients with plasmacytic myeloma who underwent surgery in the Department of Orthopedics of Qilu Hospital of Shandong University were followed up and analyzed retrospectively. Eighty-five patients were diagnosed as multiple and three as solitary. Of them, 51 were confirmed by orthopedics and 37 were treated by surgery in our center after the diagnosis of plasma cell myeloma in other departments. The main symptoms were pain in the neck, waist, back or lower limbs, neurological impairment, and pathological fractures. Of the patients with spinal lesions, 12 were associated with spinal cord dysfunction. Five were classified as grade B according to Frankel's classification, while the other seven were classified as grade C. All of the patients underwent surgical treatment at the center. Six-month Oswestry dysfunction score (ODI), Frankel score, Kamofsky score, Visual Analogue Scale/Score and Mirial score were used to evaluate the surgical outcomes. The VAS, ODI and Kamofsky scores were matched with paired t-test using SPSS statistical analysis software. The recovery of the patients was followed up and evaluated regularly. The shortest follow-up time was 6 months.20 patients with 32 lesions underwent percutaneous vertebroplasty or kyphoplasty, including 14 thoracic vertebrae and 18 lumbar vertebrae. The average VAS was 1.35 [0.67], the Oswestry score was 68.1 [8.74], the average value was 15.0 [8.17] at the second week of follow-up, and 17.1 [7.50] at the second half year of follow-up. These differences were statistically significant (p0.01). Among the patients undergoing open surgery, 6 had cervical vertebrae, 37 had thoracic vertebrae. 15 cases of lumbar spine were treated by posterior approach, 47 cases by palliative operation (simple spinal canal decompression and pedicle screw internal fixation), 11 cases by open vertebroplasty, the remaining 2 cases by single plasma cell myeloma posterior total vertebral body block / block resection, titanium mesh cement filling, pedicle screw internal fixation; 5 cases by anterior approach; Subtotal vertebrectomy, titanium mesh cement implantation, and steel/titanium plate internal fixation were performed in 4 patients. The average VAS was 6.47 (+ 1.23) before operation and 1.32 (+ 0.71) after operation. The average Kamofsky score was 39.82 (+ 8.48) before operation and 77.76 (+ 9.74) after operation. Among the patients with spinal cord dysfunction, Frankel's grade D was improved in 9 cases and E in 3 cases half a year after operation. According to the patient's self-report, the pain was better and the muscle strength was restored. Seven patients with complete cortex underwent tumor curettage, cementation and internal fixation, 2 lesions located in the proximal femur, 1 artificial femoral head replacement and 1 total hip prosthesis replacement. The follow-up period ranged from 17 to 47 months, with an average follow-up period of 31.75 months. One patient with tibial lesion was diagnosed as a single lesion by detailed examination. The right tibial myeloma was excised, the prosthesis was replaced, and the medial gastrocnemius muscle flap was transferred. The most common site of bone involvement is bone, which can lead to pain, pathological fractures and spinal cord nerve damage and other bone-related events. Some patients go to orthopedics and need surgery. At this time, definite diagnosis, prevention and treatment of bone-related events is the main work of orthopaedics. 2. Plasma cell myeloma osteopathy most often affects the spine, limbs. Long bones are relatively rare. 3. Appropriate surgical interventions are selected according to the site of tumor involvement, bone destruction, degree of spinal cord nerve damage, clinical manifestations and general condition. 4. Percutaneous vertebroplasty or percutaneous kyphoplasty can be performed in patients with spinal plasma cell myeloma, simple pathological fracture or near fracture, especially in patients with pain. Surgical treatment is necessary for patients with spinal cord nerve damage or spinal instability. In rare cases, tumor resection is necessary. 5. For long bone myeloma, the risk of fracture is high or pathological fracture has occurred, prosthesis replacement is feasible at the adjacent end of the joint, and for those located in the backbone. Internal fixation, bone cement filling bone defect. 6. Palliative surgery for multiple myeloma is not for the purpose of curing myeloma, but as an adjuvant treatment.
【學位授予單位】：山東大學
【學位級別】：碩士
【學位授予年份】：2016
【分類號】：R733.3
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