Osteosarcoma: A Multifactorial Clinical and Histopathological Study with Special Regard to Therapy and Survival

A multifactorial analysis was performed on all 153 unequivocal cases of genuine osteosarcoma recorded in the Swedish Cancer Registry for the years 1958 through 1968. Cases of so-called parosteal osteosarcoma, soft-tissue osteosarcoma and osteosarcoma secondary to Paget's disease of bone were not included. The osteosarcomas were subclassifiecl as follows: osteoblastic (69 per cent), chondroblastic (19 per cent) and fibroblastic (12 per cent). The overall 5-year survival rate was 22 per cent; 55 per cent for those who had undergone amputation above the joint proximal to the involved skeletal part, 22 per cent for those amputated on the involved skeletal part, 11 per cent for those treated with local extirpation of the tumor, and 1 per cent in cases in which the lesion was not radically removed. Tumors of the femur, humerus and scapula were as malignant as axial tumors. The former carried a 5-year survival rate of 13 per cent, regardless of whether the patients had been treated with exarticulation or amputation on the involved skeletal part. Patients with axial tumors showed a 5-year survival rate of 15 per cent. These survival data suggest that proximal amputation alone might suffice for lesions situated distally to the knee and elbow joints, while tumors in the humerus and femur should be treated with amputation combined with multicytostatic treatment or immunotherapy and axial tumors with local resection and multicytostatic or immunologic treatment.     

Osteosarcoma. A multifactorial clinical and histopathological study with special regard to therapy and survival.

A multifactorial analysis was performed on all 153 unequivocal cases of genuine osteosarcoma recorded in the Swedish Cancer Registry for the years 1958 through 1968. Cases of so-called parosteal osteosarcoma, soft-tissue osteosarcoma and osteosarcoma secondary to Paget's disease of bone were not included. The osteosarcomas were subclassified as follows: osteoblastic (69 per cent), chondroblastic (19 per cent) and fibroblastic (12 per cent). The overall 5-year survival rate was 22 per cent; 55 per cent for those who had undergone amputation above the joint proximal to the involved skeletal part, 22 per cent for those amputated on the involved skeletal part, 11 per cent for those treated with local extirpation of the tumor, and 1 per cent in cases in which the lesion was not radically removed. Tumors of the femur, humerus and scapula were as malignant as axial tumors. The former carried a 5-year survival rate of 13 per cent, regardless of whether the patients had been treated with exarticulation or amputation on the involved skeletal part. Patients with axial tumors showed a 5-year survival rate of 15 per cent. These survival data suggest that proximal amputation alone might suffice for lesions situated distally to the knee and elbow joints, while tumors in the humerus and femur should be treated with amputation combined with multicytostatic treatment or immunotherapy and axial tumors with local resection and multicytostatic or immunologic treatment.     

Osteosarcoma and Ewing's sarcoma--The most frequent malignant bone tumors in children--therapy and outcome

BACKGROUND: Osteosarcoma and Ewing's sarcoma are the most frequent malignant bone tumors in children and young adults with relatively poor overall survival rates. METHODS: Between January 1980 and December 1994, 175 children with osteosarcoma and 64 children with Ewing's sarcoma were treated at the author's institution. 22 children had synchronous metastases, 19 patients had a pathologic fracture. Both groups were treated systemically with chemotherapy regimens (COSS and CESS). Local therapy was amputation or tumor resection and endoprosthetic replacement or biological reconstruction with wide or radical resection margins. In case of Ewing's sarcoma in 35 patients postoperative radiation therapy was done. RESULTS: Five-year overall survival rate for osteosarcoma and Ewing's sarcoma patients is about 63 %, ten-year survival rate for osteosarcoma patients is 60.2 %, for Ewing's sarcoma patients 54.5 %. Prognostic factors significantly influencing overall survival rates are tumor response to chemotherapy (p values = 0.0056 and 0.013, respectively), surgical treatment with adequate resection margins (p value = 0.0001 for osteosarcoma patients) and development of postoperative metastases (p value = 0.0001 for both groups). CONCLUSION: For both groups of malignant bone tumors systemic chemotherapy as well as adequate surgical therapy are necessary to reduce the rates of local recurrences and to achieve better survival rates.     

The effect of biopsy on survival of patients with osteosarcoma.

A retrospective study of patients with osteosarcoma was undertaken to determine whether there was a relationship between biopsy and survival. Fifty-seven patients treated at the Karolinska Hospital, Stockholm, between 1938 and 1959 were included in this study, all of whom were less than thirty years old, had a metaphysial osteosarcoma in a long bone but had no pulmonary metastases at the time of diagnosis; all were treated by amputation. No clinical variants of osteosarcoma were included. Twenty-four of the fifty-seven patients had an amputation without a prior biopsy; the others had biopsies before amputation. These two groups were fairly closely matched in age, sex, site and size of tumour, and in the level of amputation; some patients in each group received radiation before operation. Evaluation of these two groups of patients revealed that the performance of a biopsy, with or without a delay of not more than thirty days between the biopsy and the definitive operation, had no adverse effect on survival.     

骨膜骨肉瘤与高度恶性表面骨肉瘤

目的报告表面骨肉瘤的两种少见亚型,即骨膜骨肉瘤和高度恶性表面骨肉瘤的诊治经验。方法回顾 5例骨膜骨肉瘤和 4例高度恶性表面骨肉瘤患者的影像学和病理学特点,并对临床治疗结果进行分析。 5例骨膜骨肉瘤患者,男 1例,女 4例;年龄 28～ 42岁,平均 35岁;肿瘤位于胫骨上段者 4例,股骨下段者 1例。 4例高度恶性表面骨肉瘤患者,男 3例,女 1例;年龄 17～ 23岁,平均 19.25岁; 4例患者肿瘤均位于股骨下段。结果 5例骨膜骨肉瘤均予以广泛切除,除 1例因局部复发行截肢术,现无瘤生存 1年 3个月外,余 4例已无瘤生存 3～ 9年,平均 5年 9个月。 4例高度恶性表面骨肉瘤患者,虽经积极综合治疗,但仅 1例无瘤生存 7年; 1例术后 2年 5个月复发而截肢,现无瘤生存 1年 9个月; 1例于术后 2年 4个月死于肺转移;另 1例在确诊后 3个月死亡。结论骨膜骨肉瘤和高度恶性表面骨肉瘤各具鲜明的影像学和病理学特点,骨膜骨肉瘤恶性程度较低,应采用以局部广泛切除为主的手术治疗,预后相对较好;而高度恶性表面骨肉瘤的生物学行为则与经典的髓内骨肉瘤相似,预后较差,必须采用手术与化疗相结合的综合治疗方法。     

老年骨肉瘤10例治疗总结

目的探讨老年骨肉瘤（≥60岁）的临床特点和治疗效果。 方法回顾性分析2007年1月至2017年3月期间山东大学齐鲁医院骨科收治的≥60岁的骨肉瘤患者10例,女性8例,男性2例,年龄60~76岁,平均（66±6）岁,病变位于股骨5例、踝关节软组织1例、多中心1例、骨盆（Ⅲ区）1例、肱骨1例、距骨1例。确诊后行截肢术2例,截肢术结合化疗2例,广泛切除术1例,广泛切除术结合化疗3例,边缘切除结合放疗1例,单纯化疗1例。 结果10例患者中,4例就诊时病史已超过6个月,2例就诊时已出现肺转移,5例合并基础疾病,2例血清ALP水平升高（>125 U/L）。影像学方面,7例为混合型,1例为溶骨型,1例为成骨型,1例位于软组织。肿瘤组织类型方面,普通型骨肉瘤7例,骨旁骨肉瘤2例,髓内高分化性骨肉瘤1例。10例患者随访3.5~124个月,平均（40±37）个月。1例接受单纯化疗的肺转移患者于明确诊断后3.5个月死亡,另1例肺转移患者接受转移灶射频消融术,随访58个月带瘤生存,1例距骨骨肉瘤复发后行截肢术。其余7例均未出现肿瘤复发或远处转移。 结论老年骨肉瘤临床较为少见,具有不同于青少年骨肉瘤的临床特点和预后,应早期明确诊断,采取适合患者自身情况的治疗方法,以尽可能降低复发和转移的发生率,延长生存期。     

单中心四肢骨肉瘤311例预后分析

 目的 探讨单中心四肢骨肉瘤的治疗、预后及生存状况。方法 回顾性分析1998年至2008年间单中心收治的311例四肢骨肉瘤患者的病历资料,记录患者的基本资料、化疗、手术、并发症、肿瘤转移及预后情况,应用Kaplan-Meier、Cox regression 等统计学方法分析各变量与预后生存的关系。结果 311例四肢骨肉瘤患者,男206例,女105例;年龄5～56岁,平均18.6岁;上肢29例,下肢282例。282例获得广泛或根治性手术,保肢手术149例,截肢手术133例。术后64例患者发生各种并发症,其中17例出现2次以上的术后并发症,25例发生肿瘤局部复发。105例获得规范化疗,206例未获得规范化疗,5年生存率分别为57.4%和36.3%。肺转移患者(76例)和无肺转移患者5年生存率分别为16.8%和50.7%。Enneking 分期ⅡB期和Ⅲ期患者5年生存率分别为44.6%和33.1%。选择保肢手术和截肢手术患者的5年生存率分别为56.6%和31.8%,由于截肢患者中有较大的比例施行了不规范化疗以及其他混杂因素导致5年生存率明显降低。Cox回归分析显示化疗不规范和发生肺转移患者预后较差。结论 新辅助化疗联合肿瘤广泛或根治性手术切除可以挽救约60%青少年四肢骨肉瘤患者的生命,肺转移和不规范化疗严重影响患者的预后。     

Metastatic tumor cells detection and anti‐metastatic potential with vesicular stomatitis virus in immunocompetent murine model of osteosarcoma

Sarcomas are associated with a high incidence of lung metastasis, which leads to a high‐risk of cancer death. This study was performed to explore the pre‐clinical theranostic potential of a novel fully functional recombinant vesicular stomatitis virus carrying imaging gene Katushka (rVSV‐K), as virotherapy and circulating tumor cells (CTCs) detection in the syngeneic mouse model of osteosarcoma with spontaneous pulmonary metastases. Recombinant VSV‐K was generated and evaluated in vitro on human and murine osteosarcoma cells. Spontaneous osteosarcoma metastases were established in immune‐competent mice by implanting subcutaneously syngeneic osteosarcoma LM8 cells. The vector was injected into the tumor‐bearing mice via jugular vein either once or repeatedly. To assess effectiveness, primary tumor growth and development of lung metastasis as well as survival were evaluated. We found that rVSV‐K efficiently replicated in and killed all osteosarcoma cell lines in time‐dependent manners. Both single or repeated systemic injections of the virus did not inhibit the growth of the primary tumor, but the repeated administration could effectively suppress the development of lung metastases and was likely responsible for the observed increase in survival. Furthermore, we demonstrated, for the first time, that CTCs in blood samples from syngeneic osteosarcoma‐bearing mice were successfully detected by utilizing rVSV‐K ex vivo. Our results show that repeated systemic injections of rVSV‐K are an effective anti‐metastatic agent against osteosarcoma in immune‐competent mice and this virus to be a useful tool for detection of osteosarcoma CTCs, suggesting that further development of future viral‐based theranostic approach in patients with osteosarcoma is warranted. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2562–2569, 2018.

     

IIB osteosarcoma. Current management, local control, and survival statistics--S?o Paulo, Brazil

Ninety-two patients with IIB osteosarcoma of the extremities were treated with intraarterial (IA) cisplatinum (CDDP) followed by surgery [amputation (61.6%) or resection with endoprosthesis (38.4%)]. Postoperative chemotherapy alternating adriamycin and CDDP was used. The total three-year survival was 62.1%, and the disease-free survival was 41.1%. The pathologic evaluation of the degree of tumor necrosis in response to the IA CDDP showed that in 53.2%, the necrosis was over 90%. The multivariate analysis of prognostic factors has shown that the highest survival was among females with tumors smaller than 15 cm. Patients with lesions equal to or larger than 15 cm were three times as likely to die of the disease. A second, more aggressive study is now underway, in which high dose methotrexate (HDMTX) is preoperatively combined with adriamycin and CDDP. Following operation, ifosfamide is added to the cases with a smaller degree of tumor necrosis, while the other group of patients will continue with HDMTX, in addition to CDDP and adriamycin (these last two drugs are used in both arms). Until now, complete remission has been achieved in 82% and 86%, respectively, with a follow-up examination varying from four to 26 months (average, 14 months). This is of extreme importance, because the majority of the authors' patients have tumors at initial evaluation larger than 10 cm in diameter.     

Intraarterial cisplatin in the management of stage IIB osteosarcoma in the pediatric and adolescent age group

Sixty patients with extremity osteosarcoma were treated with intraarterial cisplatin. This was followed by surgical resection (amputation or limb salvage) and postoperative adjuvant chemotherapy utilizing two different protocols. Seventy-five percent of patients achieved an initial response. Overall disease-free survival was 58%. The number of patients treated with limb-salvage surgery gradually increased to the extent that 80% of newly-registered patients achieved a response and were subjected to limb salvage. Disease-free survival was 48% in amputation and 68% in limb salvage. The only factors found to have prognostic significance in determining disease-free survival were extent of tumor destruction induced by preoperative chemotherapy and tumor size.     

表面骨肉瘤

目的探讨表面骨肉瘤的组织类型、临床、病理及影像学特征。方法回顾性分析经病理证实的表面骨肉瘤19例,其中骨膜骨肉瘤4例,部位分别为胫骨干中上段(3例)和腓骨下段(1例);X线片及CT显示肿物位于骨旁,外缘不规则,可见放射状骨针影;镜下为低度或中度恶性软骨肉瘤样改变。高度恶性表面骨肉瘤2例,肿物均位于股骨内侧;X线片显示肿物以广泛基底附于患骨,混杂骨膜反应;镜下显示高度恶性,似髓内型。去分化骨旁骨肉瘤1例,肿物位于股骨下端;患者曾先后4次手术,术后病理显示高分化组织内出现低分化区。经典骨旁骨肉瘤12例,肿物75%位于股骨下端干骺端后部。结果骨膜骨肉瘤4例均行保肢手术,已无瘤生存1.1～6.5年。高度恶性表面骨肉瘤2例,其中1例拒绝手术,3个月后死于肺及肝转移;另1例应用大剂量化疗及保肢治疗,现已无瘤生存19个月。去分化骨旁骨肉瘤1例,行假体旁复发性肿瘤切除,现已无瘤生存6个月。经典骨旁骨肉瘤的初始治疗均为保肢手术,其中9例随访1.2～9.6年,除1例局部复发、1例死于肺转移外,另外7例均无瘤生存。结论表面骨肉瘤四种组织类型各具有特殊性,应区别对待。骨膜骨肉瘤及经典骨旁骨肉瘤应以局部广泛切除或瘤段切除为主,预后较好;去分化型和高度恶性表面骨肉瘤恶性程度较高,预后较差。保肢或截肢均应配合有     

Extraskeletal osteosarcoma of the hand: the role of marginal excision and adjuvant radiation therapy

Background

Extraskeletal osteosarcoma of the hand is rare, and its optimal modality of local control is not currently known.

Methods

A literature search was performed to identify studies that describe the treatment and outcomes of extraskeletal osteosarcoma. A second literature search was performed to identify studies that describe the treatment and outcomes of extraskeletal osteosarcoma of the hand specifically.

Results

The role of adjuvant radiation for extraskeletal osteosarcoma is not well defined. All cases in the literature describing treatment of extraskeletal osteosarcoma of the hand utilized amputation, and none of the patients described received radiation therapy. However, there are multiple reports showing excellent local control, minimal toxicity, and superior functional outcome with limb conservation and radiation rather than amputation of the hand in pediatric and adult soft tissue sarcoma.

Conclusion

For extraskeletal osteosarcoma of the hand, we recommend a treatment approach with the goal of preservation of form and function using limb-sparing surgery and planned postoperative radiation.     

413例骨肉瘤化疗、手术和预后的10年随访研究

目的对骨肉瘤的化疗、手术及预后进行随访研究,探讨骨肉瘤治疗中影响患者预后、生存及医生治疗决策的因素。方法回顾性调查1998年1月-2008年1月单一骨肿瘤治疗中心注册的413例骨肉瘤患者的病例资料,记录患者的基本情况、手术情况、化疗情况以及随访和预后情况,比较规范化疗和未规范化疗患者局部复发、肺转移率以及生存率的差异,分析骨肉瘤治疗中存在的问题。结果 413例患者中,随访〉5个月352例,失访率14.8%;随访〉12个月251例,失访率39.2%;随访〉60个月216例,失访率47.7%。321例行手术治疗,其中截肢手术165例,保肢手术156例。126例完成规范化疗,287例由于各种原因没有完成规范化疗或未进行化疗。不规范化疗患者肺转移发生率、5年总生存率及5年总无瘤生存率均低于规范化疗患者,差异具有统计学意义（P〈0.05）。结论骨肉瘤的临床治疗存在患者就诊迟、完成规范化疗比例小、保肢率低、失访率高等问题。重视并解决这些问题对骨肉瘤患者的预后有重要意义。     

Nonmetastatic osteosarcoma of the extremity with pathologic fracture at presentationLocal and systemic control by amputation or limb salvage after preoperative chemotherapy

To determine whether a pathologic fracture in osteosarcoma of long bones has prognostic importance, and limb salvage can be safely performed in such cases, we reviewed the surgical treatment and oncologic results in 46 patients with nonmetastatic osteosarcoma of the extremity and pathologic fracture at presentation who had been treated in our Institution with neoadjuvant chemotherapy, between 1983 and 1999. Neoadjuvant chemotherapy was given according to 6 consecutive protocols. Surgery consisted of limb salvage (34 patients), amputation (11 patients) and rotationplasty (1 patient). The average follow-up was 11 (320) years. 28 patients remained continuously disease-free, 17 patients relapsed and 1 died of chemotherapy-related toxicity. Despite the high rate of limb salvage, only 2 local failures occurred, 1 after amputation and 1 after limb salvage. The 5-year disease-free survival and overall survival rateswere 59% and 65%, respectively, with no differences between amputated and resected patients. These results are similar to those obtained in 689 contemporary patients having an osteosarcoma without a pathologic fracture treated in our Institution, and using the same protocols for chemotherapy. We conclude that with neoadjuvant chemotherapy, osteosarcoma patients presenting with a pathologic fracture can be surgically treated like those with no fracture, and that limb salvage procedures do not increase the risk of local recurrence or death of these patients.     

The tumor--immunological significance of splenectomy for cancer therapy

In animal experiment, 5 X 10(5) MH-134 tumor cells were transplanted s.c. on the back of the C3H/He mice. Three, seven, 14 and 21 days after tumor transplantation, splenectomy or sham operation were performed and the tumor growth and survival days were examined in each group. As the results, the tumor growth was inhibited and the survival days prolonged not only in the group splenectomized three days but also 21 days after tumor transplantation. Clinically, the effect of splenectomy in combination with immunotherapy on cell-mediated immunity and the survival rates were studied in the gastric cancer patients of upper and middle stomach with 90 cases of stage III and 48 cases at stage IV, totalling 138 cases who underwent total gastrectomy during 1965 and 1981. Immunotherapy was conducted with immunomodulator levamisole at a daily dose of 150 mg, three consecutive days every other week. As a result, splenectomy was not effective for advanced gastric cancer at stage III and in the patients spleen should be retained for immunotherapy. Splenectomy for gastric cancer at stage IV, particularly in combination with immunotherapy, produced augmentation of cell-mediated immunity and longer survival as well. Complications caused by splenectomy were small.     

四肢、躯干恶性肿瘤的术腔加热化疗研究

自１９８９年１月至１９９６年１月,作者应用手术腔加热灌注化疗四肢,躯干恶性肿瘤７１例,其中恶性（Ⅲ级）骨巨细胞瘤２６例,恶性骨母细胞瘤３例,恶性成软骨细胞瘤１例,骨肉瘤１４例,软骨肉瘤７例,尤文氏肉瘤２例,纤维肉瘤２例,滑膜肉瘤８例,神经纤维肉瘤２例,恶性纤维组织细胞瘤５例,血管肉瘤１例。手术腔内加热温度４３℃～４５℃,顺铂２００ｍｇ。加热时间６０分钟。获访６８例,结果复发率为５．７％,转移率为１４．７％,死亡率为１６％,生存率为８４％,５年生存率为７１．４３％。作者认为,术中加热化疗对防止或减少非早期转移肿瘤的局部复发和转移是有明显效果的,对早期即发生转移的肿瘤来说,同样可以减少因肿瘤细胞残留所引起的术后复发和转移,而对术前已发生转移的病灶则无作用。     

Nonmetastatic osteosarcoma of the extremity with pathologic fracture at presentation: local and systemic control by amputation or limb salvage after preoperative chemotherapy

To determine whether a pathologic fracture in osteosarcoma of long bones has prognostic importance, and limb salvage can be safely performed in such cases, we reviewed the surgical treatment and oncologic results in 46 patients with nonmetastatic osteosarcoma of the extremity and pathologic fracture at presentation who had been treated in our Institution with neoadjuvant chemotherapy, between 1983 and 1999. Neoadjuvant chemotherapy was given according to 6 consecutive protocols. Surgery consisted of limb salvage (34 patients), amputation (11 patients) and rotationplasty (1 patient). The average follow-up was 11 (3-20) years. 28 patients remained continuously disease-free, 17 patients relapsed and 1 died of chemotherapy-related toxicity. Despite the high rate of limb salvage, only 2 local failures occurred, 1 after amputation and 1 after limb salvage. The 5-year disease-free survival and overall survival rates were 59% and 65%, respectively, with no differences between amputated and resected patients. These results are similar to those obtained in 689 contemporary patients having an osteosarcoma without a pathologic fracture treated in our Institution, and using the same protocols for chemotherapy. We conclude that with neoadjuvant chemotherapy, osteosarcoma patients presenting with a pathologic fracture can be surgically treated like those with no fracture, and that limb salvage procedures do not increase the risk of local recurrence or death of these patients.     

The treatment of soft-tissue sarcomas of the extremities: prospective randomized evaluations of (1) limb-sparing surgery plus radiation therapy compared with amputation and (2) the role of adjuvant chemotherapy.

Between May 1975 and April 1981, 43 adult patients with high-grade soft tissue sarcomas of the extremities were prospectively randomized to receive either amputation at or above the joint proximal to the tumor, including all involved muscle groups, or to receive a limb-sparing resection plus adjuvant radiation therapy. The limb-sparing resection group received wide local excision followed by 5000 rads to the entire anatomic area at risk for local spread and 6000 to 7000 rads to the tumor bed. Both randomization groups received postoperative chemotherapy with doxorubicin (maximum cumulative dose 550 mg/m2), cyclophosphamide, and high-dose methotrexate. Twenty-seven patients randomized to receive limb-sparing resection and radiotherapy, and 16 received amputation (randomization was 2:1). There were four local recurrences in the limb-sparing group and none in the amputation group (p1 = 0.06 generalized Wilcoxon test). However, there were no differences in disease-free survival rates (71% and 78% at five years; p2 = 0.75) or overall survival rates (83% and 88% at five years; p2 = 0.99) between the limb-sparing group and the amputation treatment groups. Multivariate analysis indicated that the only correlate of local recurrence was the final margin of resection. Patients with positive margins of resection had a higher likelihood of local recurrence compared with those with negative margins (p1 less than 0.0001) even when postoperative radiotherapy was used. A simultaneous prospective randomized study of postoperative chemotherapy in 65 patients with high-grade soft-tissue sarcomas of the extremities revealed a marked advantage in patients receiving chemotherapy compared with those without chemotherapy in three-year continuous disease-free (92% vs. 60%; p1 = 0.0008) and overall survival (95% vs. 74%; p1 = 0.04). Thus limb-sparing surgery, radiation therapy, and adjuvant chemotherapy appear capable of successfully treating the great majority of adult patients with soft tissue sarcomas of the extremity.     

Histological studies of the effect of intra-operative irradiation on osteosarcoma

At the Department of Orthopaedic Surgery of Kyoto University Hospital, intra-operative radiotherapy by the high dose electron irradiation has so far been used in treating patients with osteosarcoma. The dose distribution was calculated by CT-number so that the focus was subject to at least 80% of the irradiation doses and the surgically opened lesion was irradiated with 5,000 rad of 12-26 MeV electron beams. In order to accurately assess its therapeutic effect, histological studies were conducted on 9 patients who underwent en bloc resection or amputation following irradiation treatment for osteosarcoma. Method The excised specimen was sagittally cut in half and was fixed in 10% neutral buffered formalin. The specimen was cut into 5 mm thick sections corresponding to CT cross sections. At the border region between irradiated and non-irradiated fields, specimens were prepared using sagittal sections to compare the histological findings of both fields. After all specimens were carefully macroscopically examined and then photographed with soft-X-ray film, some of them were prepared as non- delimed specimens in polyester resin and were observed by contact microradiography and fluorescent microscopy. The remaining specimens after deliming in Plank - Rychlo solution were sliced to 4-8 micron thick for study as large specimen stained with hematoxylin and eosin. Four patients had been administered tetracycline 3 days preoperatively. Results Histologically the changes of the specimens were evaluated using the Oohoshi and Shimosato 's criteria for the histological effects of irradiation. In two of the 9 patients, who had received unidirectional irradiation, the survival of Grade 2a-2b tumor tissue was observed in the superficial layers both inside and outside the periosteum. Six patients who were irradiated from both sides or three directions, showed complete necrosis in extremely small areas of Grade 2b-3 change of tumor cells. Only one of these 9 patients had a local recurrence after the irradiation. Marked fluorescence was observed in the recurrent tissue by tetracycline labeling, but no fluorescence was observed in any of the other cases in the tumorous tissues which had fallen within the range of irradiation. These findings strongly suggest that intra-operative irradiation is extremely effective in controlling local osteosarcoma lesion in the extremities.     

Telangiectatic osteosarcoma of the extremity: Neoadjuvant chemotherapy in 24 cases

Between April 1990 and December 1994, we treated 24 patients with telangiectatic osteosarcoma (TO) of the extremities with neoadjuvant chemotherapy using 2 protocols. Surgery consisted of limb salvage in 21 patients and amputation or rotation plasty in 3. The histologic response to chemotherapy was good (90% or more tumor necrosis) in 23 patients, of whom 12 had total necrosis. With a mean follow-up of 74 (60-96) months, 20 patients remained continuously free of disease and 4 relapsed with lung metastases. There were no local recurrences. Comparing these results to the ones achieved in 269 contemporary patients with conventional osteosarcoma of the extremities using the same protocols for chemotherapy, we found a significantly better histologic response to chemotherapy (96% vs 68% of good histologic response; p = 0.004) and disease-free survival (83% vs 55%; p = 0.01) in the TO group. We conclude that TO, once considered a lethal tumor, seems to be even more sensitive to chemotherapy than conventional osteosarcoma, and that most of these patients may be cured without amputation.