浆细胞骨髓瘤相关骨质病变的诊断和外科治疗策略

发布时间：2018-09-01 10:22

【摘要】：背景骨髓中单克隆浆细胞异常大量增殖并分泌单克隆免疫球蛋白造成的恶性肿瘤,称为浆细胞骨髓瘤。在有些国家的血液系统恶性肿瘤中,浆细胞骨髓瘤的发病率可排在第二位,囊括多种类型,而又以多发性骨髓瘤(multiple myeloma, MM)最多见,可发生于全身各处的骨骼。另外,临床上亦有仅累及单一病灶的孤立性骨髓瘤(solitary myeloma, SM,又称为孤立性浆细胞瘤)。病变以中轴骨多见,首先侵犯松质骨,然后逐渐破坏皮质骨。MM发病率较高,约为0.7-3.3/100000,SM仅占所有骨髓瘤的2%,有文献报道2/3的SM将最终进展为MM。而且浆细胞骨髓瘤的发病率随着人口老龄化还在不断增高。浆细胞骨髓瘤分泌的细胞因子会导致破骨细胞的活动加强及成骨细胞活动的减弱,进而引起骨吸收和骨形成失衡,最终导致骨痛、全身弥漫性骨质疏松和骨质破坏、高钙血症及其他骨的相关事件(病理性骨折、脊柱稳定性丧失、脊髓和神经根受压等)等。如果不给予有效的针对治疗,大约50%的病人在疾病发展过程总会出现至少一种骨骼相关事件。病理性骨折等事件的发生将在很大程度上危及患者的生存质量和预期寿命,曾有研究发现出现病理性骨折的浆细胞骨髓瘤患者的死亡率比未出现病理性骨折的患者要高20%。目前对于浆细胞骨髓瘤患者手术治疗的必要性,各种手术方式的适应症,手术对患者生活质量及预后的作用还没有确定的结论。有研究认为对浆细胞骨髓瘤进行手术治疗能够改善患者生存质量,也有研究认为孤立性浆细胞瘤的相关骨病变并不需要外科治疗。目的通过搜集并探讨在山东大学齐鲁医院骨科就诊并接受手术治疗的浆细胞骨髓瘤患者的临床表现、诊断方法、外科治疗指征、手术方式选择及手术后患者的恢复情况,评估不同外科治疗方法的安全性和必要性,系统地分析浆细胞骨髓瘤相关骨骼病变的外科综合治疗方案,为骨科医生对骨髓瘤相关骨骼病变的治疗提供参考,避免误诊、治疗不足和过度。方法对2005年5月至2015年5月于山东大学齐鲁医院骨科就诊并行手术治疗的88名浆细胞骨髓瘤病人进行随访,并回顾性对既往收集到的资料进行分析。其中女性患者39例,男性患者49例,骨科首诊年龄30～84岁(平均60.0岁)。以脊柱病变就诊者78例,以下肢长骨病变就诊者10例(股骨9例,胫骨1例)。最终确诊多发者85例,单发者3例。其中51例为骨科确诊,37例为其他科室浆细胞骨髓瘤确诊后于本中心接受手术治疗。病人就诊的主要症状有颈、腰、背部或下肢疼痛,神经功能损害和病理性骨折。以脊柱病变就诊者中,共有12例合并脊髓功能损害。5例按照Frankel分级可归为B级,其他7例则为C级。这些患者都在本中心接受了外科手术治疗。搜集记录患者术前及术后2周、半年的Oswestry功能障碍评分(ODI)、Frankel分级、Kamofsky评分、视觉模拟评分(Visual Analogue Scale/Score)和Mirel评分等评价手术效果,其中对于VAS、ODI和Kamofsky评分,使用SPSS统计分析软件进行配对t检验。对患者的恢复情况进行定期的随访和评估。结果患者手术后的随访时间最短6个月。20例病人共32个病变的椎体行经皮椎体成形术或者是椎体后凸成形术,共包括胸椎14个,腰椎18个。对于这批病人,术前VAS 4-8分,平均6.45±1.05分,术后两周的评分是0-3分,平均为1.05±0.89,随访至术后半年计算VAS平均值为1.35±0.67；手术前所有患者Oswestry评分计算的平均值是68.1±8.74分,随访术后第二周的平均值降为15.0±8.17,至术后半年再次随访时则至17.1±7.50,这些差异经计算具有统计学意义(p0.01)。行开放手术的患者中,颈椎6例,胸椎37例,腰椎15例。其中49例患者行后路手术,47例为姑息性手术(单纯椎管减压椎弓根钉内固定术),其中又有11例同时行开放椎体成形术,剩余2例单发浆细胞骨髓瘤行后路全椎体分块／整块切除、钛网骨水泥填充、椎弓根钉内固定术；5例行前路椎体次全切除,钛网骨水泥植入,钢／钛板内固定术；4例为前后路联合术。术前平均VAS 6.47±1.23,术后半年为1.32±0.71。术前平均Kamofsky评分39.82±8.48,手术半年后改善为77.76±9.74。这些术后改善在统计学上具有意义(p0.01)。而对于12例有明显脊髓功能损害的患者中,9例患者的Frankel分级手术后半年改善为D级,3例患者改善为E级,根据患者自述疼痛比术前要好转,肌力也有恢复。单发者接受术后局部疼痛等症状消失,截止随访结束未见复发。以股骨病变就诊者9例,Mirel评分均大于9分。7例骨皮质完整者行肿瘤刮除、骨水泥填充、内固定术,2例病变位于股骨近端,1例患者接受人工股骨头置换术,1例则接受全髋假体置换。术后随访时间17～47个月,平均随访时间31.75个月。随访期间患者,1例失访,无二次手术,无死亡病例发生,功能恢复良好。其中以胫骨病变就诊的患者1例,经详细检查确诊为单发病变,行右胫骨骨髓瘤切除、定制假体置换,腓肠肌内侧肌瓣转移术。术后随访12个月,一般情况可,无复发,无远期并发症。结论1、浆细胞骨骨髓瘤是一种血液系统疾病,最常见的受累部位是骨骼,可导致疼痛、病理骨折和脊髓神经功能损害等骨骼相关事件。部分病人到骨科就诊并需要手术治疗,此时,明确诊断、防治骨相关事件是骨科医生的主要工作。2、浆细胞骨髓瘤骨质病变最常累及脊柱,四肢长骨相对少见。3、根据肿瘤累及部位、骨质破坏情况、脊髓神经损害程度、临床表现及全身状况选择合适的手术干预方式。4、对脊柱浆细胞骨髓瘤,单纯病理骨折或濒临骨折,尤其伴有疼痛的患者可进行经皮椎体成形术或经皮椎体后凸成形术治疗,对于合并有脊髓神经损害者或脊柱明显不稳者,行椎管减压和脊柱固定等开放手术十分必要。少数情况下行肿瘤切除术。5、对长骨骨髓瘤,骨折风险较高或已经发生病理性骨折者,邻近关节端者可行假体置换术,位于骨干者可行内固定,骨水泥填充骨质缺损。6、针对多发性骨髓瘤的手术为姑息性手术,并不是以治愈骨髓瘤为目的,是作为一种辅助的治疗方式。
[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.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R733.3

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