漿細(xì)胞骨髓瘤相關(guān)骨質(zhì)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(xì)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(xì)胞骨髓瘤。在有些國家的血液系統(tǒng)惡性腫瘤中,漿細(xì)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(xì)胞瘤)。病變以中軸骨多見,首先侵犯松質(zhì)骨,然后逐漸破壞皮質(zhì)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(xiàn)報道2/3的SM將最終進(jìn)展為MM。而且漿細(xì)胞骨髓瘤的發(fā)病率隨著人口老齡化還在不斷增高。漿細(xì)胞骨髓瘤分泌的細(xì)胞因子會導(dǎo)致破骨細(xì)胞的活動加強及成骨細(xì)胞活動的減弱,進(jìn)而引起骨吸收和骨形成失衡,最終導(dǎo)致骨痛、全身彌漫性骨質(zhì)疏松和骨質(zhì)破壞、高鈣血癥及其他骨的相關(guān)事件(病理性骨折、脊柱穩(wěn)定性喪失、脊髓和神經(jīng)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(xiàn)至少一種骨骼相關(guān)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(zhì)量和預(yù)期壽命,曾有研究發(fā)現(xiàn)出現(xiàn)病理性骨折的漿細(xì)胞骨髓瘤患者的死亡率比未出現(xiàn)病理性骨折的患者要高20%。目前對于漿細(xì)胞骨髓瘤患者手術(shù)治療的必要性,各種手術(shù)方式的適應(yīng)癥,手術(shù)對患者生活質(zhì)量及預(yù)后的作用還沒有確定的結(jié)論。有研究認(rèn)為對漿細(xì)胞骨髓瘤進(jìn)行手術(shù)治療能夠改善患者生存質(zhì)量,也有研究認(rèn)為孤立性漿細(xì)胞瘤的相關(guān)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(xué)齊魯醫(yī)院骨科就診并接受手術(shù)治療的漿細(xì)胞骨髓瘤患者的臨床表現(xiàn)、診斷方法、外科治療指征、手術(shù)方式選擇及手術(shù)后患者的恢復(fù)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(xì)胞骨髓瘤相關(guān)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(guān)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(xué)齊魯醫(yī)院骨科就診并行手術(shù)治療的88名漿細(xì)胞骨髓瘤病人進(jìn)行隨訪,并回顧性對既往收集到的資料進(jìn)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(xì)胞骨髓瘤確診后于本中心接受手術(shù)治療。病人就診的主要癥狀有頸、腰、背部或下肢疼痛,神經(jīng)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(shù)治療。搜集記錄患者術(shù)前及術(shù)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(shù)效果,其中對于VAS、ODI和Kamofsky評分,使用SPSS統(tǒng)計分析軟件進(jìn)行配對t檢驗。對患者的恢復(fù)情況進(jìn)行定期的隨訪和評估。結(jié)果患者手術(shù)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(jīng)皮椎體成形術(shù)或者是椎體后凸成形術(shù),共包括胸椎14個,腰椎18個。對于這批病人,術(shù)前VAS 4-8分,平均6.45±1.05分,術(shù)后兩周的評分是0-3分,平均為1.05±0.89,隨訪至術(shù)后半年計算VAS平均值為1.35±0.67；手術(shù)前所有患者Oswestry評分計算的平均值是68.1±8.74分,隨訪術(shù)后第二周的平均值降為15.0±8.17,至術(shù)后半年再次隨訪時則至17.1±7.50,這些差異經(jīng)計算具有統(tǒng)計學(xué)意義(p0.01)。行開放手術(shù)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(shù),47例為姑息性手術(shù)(單純椎管減壓椎弓根釘內(nèi)固定術(shù)),其中又有11例同時行開放椎體成形術(shù),剩余2例單發(fā)漿細(xì)胞骨髓瘤行后路全椎體分塊／整塊切除、鈦網(wǎng)骨水泥填充、椎弓根釘內(nèi)固定術(shù)；5例行前路椎體次全切除,鈦網(wǎng)骨水泥植入,鋼／鈦板內(nèi)固定術(shù)；4例為前后路聯(lián)合術(shù)。術(shù)前平均VAS 6.47±1.23,術(shù)后半年為1.32±0.71。術(shù)前平均Kamofsky評分39.82±8.48,手術(shù)半年后改善為77.76±9.74。這些術(shù)后改善在統(tǒng)計學(xué)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(shù)后半年改善為D級,3例患者改善為E級,根據(jù)患者自述疼痛比術(shù)前要好轉(zhuǎn),肌力也有恢復(fù)。單發(fā)者接受術(shù)后局部疼痛等癥狀消失,截止隨訪結(jié)束未見復(fù)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(zhì)完整者行腫瘤刮除、骨水泥填充、內(nèi)固定術(shù),2例病變位于股骨近端,1例患者接受人工股骨頭置換術(shù),1例則接受全髖假體置換。術(shù)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(shù),無死亡病例發(fā)生,功能恢復(fù)良好。其中以脛骨病變就診的患者1例,經(jīng)詳細(xì)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(nèi)側(cè)肌瓣轉(zhuǎn)移術(shù)。術(shù)后隨訪12個月,一般情況可,無復(fù)發(fā),無遠(yuǎn)期并發(fā)癥。結(jié)論1、漿細(xì)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(dǎo)致疼痛、病理骨折和脊髓神經(jīng)功能損害等骨骼相關(guān)事件。部分病人到骨科就診并需要手術(shù)治療,此時,明確診斷、防治骨相關(guān)事件是骨科醫(yī)生的主要工作。2、漿細(xì)胞骨髓瘤骨質(zhì)病變最常累及脊柱,四肢長骨相對少見。3、根據(jù)腫瘤累及部位、骨質(zhì)破壞情況、脊髓神經(jīng)損害程度、臨床表現(xiàn)及全身狀況選擇合適的手術(shù)干預(yù)方式。4、對脊柱漿細(xì)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(jìn)行經(jīng)皮椎體成形術(shù)或經(jīng)皮椎體后凸成形術(shù)治療,對于合并有脊髓神經(jīng)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(shù)十分必要。少數(shù)情況下行腫瘤切除術(shù)。5、對長骨骨髓瘤,骨折風(fēng)險較高或已經(jīng)發(fā)生病理性骨折者,鄰近關(guān)節(jié)端者可行假體置換術(shù),位于骨干者可行內(nèi)固定,骨水泥填充骨質(zhì)缺損。6、針對多發(fā)性骨髓瘤的手術(shù)為姑息性手術(shù),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(xué)位授予單位】：山東大學(xué)
【學(xué)位級別】：碩士
【學(xué)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(xué)位授予單位】：山東大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2016
【分類號】：R733.3
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相關(guān)碩士學(xué)位論文 前2條
1 張慶宇;漿細(xì)胞骨髓瘤相關(guān)骨質(zhì)病變的診斷和外科治療策略[D];山東大學(xué);2016年
2 曹旭;脊柱漿細(xì)胞骨髓瘤中微血管密度與NF-κB亞型及骨病關(guān)系的探討[D];第二軍醫(yī)大學(xué);2010年
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