目的 探讨多发性骨髓瘤外科治疗的手术指征、方式和效果。方法 总结分析了29例孤立性骨髓瘤和多发性骨髓瘤患者的临床表现及外科治疗情况。本组病例男17例，女12例。年龄38-76岁，平均59.5岁。原发病灶位于脊柱9例，肋骨1例，肱骨2例，股骨上端2例，股骨干4例， 骨盆5例，骶骨6例。这29例患者分别进行了下列外科治疗：行单纯病灶清除12例，其中6例为骶骨骨髓瘤，5例炎骨盆部骨髓瘤；行柱前路病灶清除减压、钛网置和钢板内固定6例； 行脊柱后路病灶清除减压、经椎弓根内固定3例；5例病理性骨折患者分别行肿瘤刮除、骨水泥填充，髓内钉或DHS内固定；3例患者行肿瘤切除，人工假体置换。文章评估了手术后疼痛、神经损害症状、脊柱不稳等症状的改善，生活质量及生存情况。结果 疼痛改善最明显，所有患者均有疼痛减轻。3例截瘫患者，一例由Frankal分级B级变为C级，2例由C级变为D级。术后平均随访1.5年。3例局部复发。结论 对有严重神经功能损害和严重影响患者生存质量的合并症的多发性骨髓瘤患者来说，外科手术治疗是一种有效可行的治疗方法，再结合化疗和放疗，对改善患者的生活质量和延长生存期是非常有意义的。

The INK4A gene, localized to human chromosorme 9p21, encodes P16INK4A, a tumor suppressor that functions at least in part through the inhibition of CDK4, a cyclin-dependet kinase encoded by a gent at 12q13. To examine INK4A gene alterations in uncultured samples of osteosarcoma and the relationship between INK4A adn CDK4 alterations, we ana-lyzed the INK4A and CDK4 genes in 87 specimens from 79 patients. INK4A deletion and CDK4 gene amplification were determined by quantiattive Southern blot analysis. INK4A exon 2 was screened for mutation by polymerase chain reaction and single-strand comformational polymorphism analysis. Methylation at the CpG island in INK4A, associated with loss of p16INK4A expression, was assessed by Southern blot analysis using methylation-sensitive restriction enzymes. INK4A deletion (4/55) or rearrangement (1/55) was found in 5 of 55 cases. No INK4A exon 2 poitnt mutations and methyl-ation were detected. CDK4 gene amplification was found in 6 of 67 samples, but not in tumors with INK4A alteration. Amplification analysis of other genes at 12q13 (GLI, CHOP, HMGI-C and MDM2) in these 6 cases supports the view that CDK4 and MDM2 are independent targets for amplification, with variable amplification of the intervening region comtain-ing HMGI-C. Of 46 patients studied for both INK4A alterations and CDK4 amplification, the tumors in 22% contained one or the other. The prevalence of these alterations, in conjunction with the reported inactivation of RB in up to 80% of cases, suggests that genetic lesions deregulating the G1 to S cell cycle checkpoint may be an almost constant feature in the pathogenesis of osteosarcoma. Int. J. Cancer 80: 199-204, 1999.

High-dose methotrexate is a major component of cur-rent protocols for the treatment of osteosarcoma, but some tumors seem to be resistant. Potential mechanisms of resist-ance include decreased transport throughthe reduced folate carrier (RFC) and increased expression of dihydrofolate reductase (DHFR). To investigate methotrexate resistance, tumors were obtained from 42 patients with high-grade osteosarcoma. RFC and DHFR mRNA expression were studied by semiquantiiative reverse transcription-PCR. The PFC and DHFR genes were studied for deletions and am-plification bySouthern blot. Thirteen of 20 (65%) osteosar-coma samples were found to have decreased RFC expression at the time of intial biopsy. At definitive surgery and re-lapse, 10 of 22 (45%) were found to have decreased RFC expression. Seventeen of 26 (65%) samples with a poor response to chemotherapy had decreased RFC expression, response to chemotherapy had decreased RFC expression, whereas 5 of 14 (36%) samples with a good response had a decrease (p=0.03). None of the samples had an RFC gene deletion. Two of 20 samples (10%) showed increased DHFR expression at inital biopsy. The frequency of increased DHFR expression was significanfly higher inmetastatic or recureent tumors (62%, p=0.014). None of the samples showed evidence of DHFR gene amplification. The high frequency of decreased RFC expression in the biopsy mate-rail suggests that impaired transport of methotrexate is a common mechanism of intrinsic resistance in osteosarcoma. Increased DHFR expression in the pulmonary metastases may be a mechanism of acquired methotrexate resistance or a difference between primary and metastatic lesions.

BACKGROUND. The primary genetic alteration, in > 95% of Ewing sarcomas (ES) is involoed in progression of ES are not well understood. A recent study found loss of the negative cell cyde rcgulator gene INK4A in 8 at 27 FS samples (13%) To confirm these findings and cvaluate their prognostic Significanoe, Lhe authors studied INK4A deletion in 41 ES samples from 39 patiens. METHODS Using Soulthem blot analysis with an INK4A p16 cDNA probe, the control probe and compared with nondeleted eonrol DNA; > 50% signal reduction was scored as evidence of deletion All NS tumor DNA samples previously were confirmed to have EWS rearrangremetnts on the same Soulhum blots, Using a cDNA probe spanning the EWS breakpoint region. RESULTS. Tumors from 7 Datients (18%) showed INK4A deletion indenendent of tasis INK4A was. strong negative facror for disease specific surviat in Univafate CONCLUSIONS. INK4A deletions appear to be the most frequent seeondary molec-ular genetic alteration faund la date in ES. Their possible clinical usefulness in identifying a subset or ES patents with poor prognosis merits systematic prospec tive analysts See related article on pages 783-92.

Bone morphogenetic proteins, which are capable of inducing mesenchymal tissue to form bone in mammals, have been implicated as important in normal skeletal developmetl. The expession of bone morphogenentic proteins and their recep-tors were studied In 36 osteosarcoma speelmens, six Ewing' s sarcomas, 20 synuvial sarcomas, and 20 ehondrcomas by reverse transcriptase-polyme rase chain reaction, and the flndings were co.elated with clinical data. Bane morphogene-tic protein-2, and -4 messages were detected in most sarcoma samples. Bone morphogenetic pratein-6 exprssion was detected in 22 of 32 os-teosarcomas and seven of eight chondrco-mas. Bone morphogenetic protein-7 and recep-tar IB were not detected in sarcoma sumples but were detected in three osteosarcoma cell lines and one malignant fibrous histiocytoma cetlline. Expression of bone morphogenetie protein re-ceptor II was found in 25 of 36 ostesarcomas, eight of 20 chondrosarcomas, four of six Ewing' s sarcomas, and 15 of 20 synovial sarcoma sam-pies. Expression of hone morphngenetic protein type 11 receptor was found to currelate with me-tastasis in osteosarcomas, which suggests that the hone morphogenetic protein pathway may participate in tumor aggressivenss or progres-sion. The expression of bone morphogenetic pro-rein receptor 11 in metastatic synovial sarcoma and dedifferentiated chondrosarcoma Iesions also supports this hypathesis. The current study showed that the ligauds fur hone morphogenetic protein receptors, bone morphagenetic proteins-2, -4, and -6 also are expressed in ostecrcoma and other other sarcoma tissues, indicating a potenlial for autocrine or paracrine growth stimulation in these tumors.

objective To analyse comparatively the relevant data from bone tumor registnies in China, Japan, and the United States. Methods The data of 38 959 histologically confirmed priory bone tumors collected by the Chinese Bone Tumor Registry 1957-1988. 20 272 collected by the Japanese Bone Tumor Registry 1972-1990, and 11087 diagnosed and treated at Mayo Clinic, USA were used for comparative analysis by race, age, sex and skeletal distribution For reliability, we used ratios of different tumors to osteosarcoma for frequency analysis. We also included some data from the SEER 1973-1987 as well as from Memorial Sloan-Kettering Caneer Center, USA Results The relative freqency of oseosarcoma (OS) is higher in China and Japan 1hart in the United $tates. There were only limited number of OS patients aged over 50 years in Chlaese and Japanese groups, which might be due to the lower incidence of OS subsequent to Paget' s disease in Asans. More osteosarcoma occurred in the flat bones in the Americans than in the Chinese and Japanese. The relative frequency of chondrosarcoma (CS) was higher in the Arrlerican group than in the Asian groups. The average age of CS patient was younger in the Chinese than in the Japanese and the Americans. The data confimed the previous report that the incidece of Ewing sarcoma was higher in westem people than in Asians. The data showed that the comparative frequency of cherdoma is higher in the Americans than in the ASianS and that the incidence of giant cell tumor of bone is higher in the Chinese and Japansee than in the Americans. Concluson The findings from this analysis provide useful information for the epdemiolegic study and the clinical digansis of bone tumors.

Objective To observe the in vitro growth inhibitory and apoptois-inducing effcts of paclitaxel on the human osteosarcoma cell line U-2 OS Methods U-2 US cells were treated with vadous concentrations of paclitaxel Proliferatien was determined by cell count in a neubauer eytometer chamber Viability was assessed by trypan blue dye exclusion Paclitaxel-induced morphotogic alterations were visualized using light and transmission electron microsopy. The extent of paclitaxel-induced apoptosis was determined by flow cytometry and immunohistochemical duration (Td T-mediated dUTP nick end labeling technique, TUNEL) Results The cells treated with pacifies[ initially showed G2/M arrest, which was followed by apoptosis. The characteristic apoptotic changes, including nuclear disintegration and chromatin agglomeration, were displayed. Large amounts of micronuclei cells appeared, something not observed in those cells treated with eispiatin and adriamycin for contrast. Also, extensive DNA-cleavage was detected using TUNEL. Conclusion This study demonstrates that pacliaxel has an apoptotic-inducing effect on osteosarcoma cells through the initiation of G2/M arrest and inhibiting mitosis in both a time-depsndent and dose-deoendent manner.

目的 探讨骶骨肿瘤治疗的有效途径。方法 回顾1996年7月～2001年12月119例间骶骨肿瘤的治疗结果及经验.手术时平均年龄为57岁（18～80）；男性72例，女性47例。其中，脊索瘤52例、骨巨细胞瘤16例、神经纤维瘤5例、转移瘤23例、骨髓瘤9例、骨母细胞瘤2例、动脉瘤样骨囊肿5例、骨肉瘤3例、软骨肉瘤4例。采用后方人路例，前后路联合切口36例。29例接受第23次手术的患者，16例术前接受过放疗。结果3例死于围手术期并发症，多数转移瘤及骨髓瘤死于术后1～3年。3例骨肉瘤中2死亡，带瘤生存1例。4例软骨肉瘤术后均反复科长发，3例死亡，带瘤生存1例。52例脊索瘤中，3例死于转移性脊索瘤，3例死于肿瘤反复复发所致衰竭。在其余46例患者中，31例无瘤生存平均随访时间为3年半，没有月光瘤局部复发迹象。15例脊萦瘤患者均出现局部复发。双侧S3以上神经根基本保全的患者中， 术后膀胱控尿功能及大便控制基本正常，2例仅保全S1神经根或更高位神经根的患者，均出现膀胱控尿功能 及大便控制能力受损，术后长期放置尿管，均未接受结肠造瘘手术。结论 骶尾部肿瘤的最佳治疗为广泛的手术切除术后国用辅助放化疗可降低度复发率，但会影响二次手术的显露及术后切口愈合。即使是肿瘤较大的患者，切除范围要达到S1或S2水平，后方人路仍能完成手术，对于动肪瘤样骨囊肿、骨巨细胞瘤或肿瘤巨大者，建议彩前后路联合人路，结扎双侧髂内动脉或临时阻断腹主动脉，减少术中出量。通过恰当的切创造的辅助放化疗可以有产地缓解症状，控制肿瘤的生长。

目的：脊柱转移瘤可引起顽固性疼痛及脊髓压迫，其外科治疗仍存在许多争议，探讨脊柱转移瘤外科治疗的临床效果。方法：自1998年7月～2001年7月，北京大学人民医院骨髓肿瘤科手术治疗脊柱转移瘤患者62例，包括颈椎转移6例，胸椎转移37例，腰椎转移19例。无明显神经系统受累者19例：出现神经系统受损者43例，三个脊椎节段者5例。结果：62例患者中，58例（94%）术后疼痛得到缓解。43例有神经功能损害的患者中，33例术后麻痹状改善。25例术前膀胱及直肠功能受损的患者中，术后12例膀胱及直肠功能明显改善。术前Frankel A、B级的患者，5例术后恢复到E级或D级，9例改善为C或D级。结论：从肢体功能减退到完全瘫痪所经历的时间是了重要的预后因素，在48h内完全瘫痪为预后不良的重要因素：膀胱和直肠功能的完全丧失也提示预后不良。甲状腺癌和乳腺癌的脊柱转移一般预后较好，肺癌和肝癌的脊柱转移通常存活期较短。

目的：将切除的肿瘤骨去除瘤组织、经灭活处理后植回原位，重建骨骼的缺损。方法：1997年7月～2000年12月，对24例长骨恶性肿瘤患者施行了广泛切除加灭活骨移植物复合假体重建骨缺损的治疗。其中成骨肉瘤17例，骨转移癌7例。肿瘤广泛切除后，清除瘤骨上所有的肿瘤组织，开槽打通髓腔，再经200g/L高渗盐水浸泡30min，体积分数95%的酒精浸泡20min,然后植回原位。13例采用灭活肿瘤患者术前均行两个周期的规范化疗。结果：所有患者均获随访，中位访时间为2.5年。术后1例患者发生灭活骨与宿主骨接合下的连接失败。2例患者在术后6个月～2年内局部复发，1例接受了肿瘤再切除治疗、另1例接受了截肢手术。无一例发生灭活骨的疲劳性骨折。术后6个月时重建关节的功能评分均在25分以上。结论：应用自体灭活骨代替同种异体移植物进行复合移植重建骨缺损的优点包括：（1）相对于同种异体骨，除低了骨连接部的不愈合率；（2）降低了局部感染率；（3）造价低；（4）经过平均2.5年的随访，未发现灭活骨有异体骨移植常见的骨吸收现象。体外实验证实200g/L高渗盐水对骨的渗透力较强，肯有良好的灭活效果。与酒精联合应用进一步降低了局部复发率。全部病例中只有2例局部复发，占9%，达到国际上对保肢术规定的局部复发率的要求。