新辅助化疗结合保肢手术治疗骨肉瘤的临床观察

目的 探讨新辅助化疗结合保肢手术治疗骨肉瘤的临床疗效.方法 对23例四肢骨肉瘤患者实施保肢手术,并分别于术前、术后进行辅助化疗.患者出院后加强随访,并对恢复情况进行功能评定.结果 随访期内患者无瘤生存率为69.57%(16/23),术后功能评定优9例、良7例,优良率为69.57%(16/23).结论 新辅助化疗结合保肢手术治疗骨肉瘤患者疗效较好,值得临床推广应用.     

四肢骨肉瘤保肢治疗的疗效观察

目的评价采用保肢和截肢术结合化疗对Ⅱ期四肢骨肉瘤患者的临床疗效。方法分析1996年1月～2007年7月山西医科大学第二医院骨科收治确诊的68例肢体骨肉瘤患者的临床资料,其中48例行保肢术治疗,20例行截肢术。术前、术后均进行化疗。63例患者获随访,随访时间6～63个月,平均38．5个月。将随访时间达3年的53例骨肉瘤患者分为保肢组和截肢组,以3年生存率、局部复发率以及术后的功能恢复评价为指标进行比较。结果在53例肢体骨肉瘤患者中,保肢组3年生存率为51．4％,局部复发率为8％,按照国际保肢协会推荐使用的肿瘤术后功能重建评价系统平均为26分。截肢组3年生存率为50％,局部复发率为6％,术后功能评分平均为12分。统计学检验比较保肢术和截肢术术后3年生存率无显著性差异（P〉0．05）。结论在术前、术后辅助化疗的基础上,保肢组的3年生存率、局部复发率与截肢组相似,并且保肢术后功能恢复满意,故采用保肢术治疗同期肢体骨肉瘤患者疗效优于截肢术。     

Prognostic factors for osteosarcoma of the extremity treated with neoadjuvant chemotherapy: 15-year experience in 789 patients treated at a single institution

BACKGROUND: The evaluation variables influencing systemic and local recurrence and final outcome are extremely important in defining risk-adapted treatments for patients with nonmetastatic osteosarcoma of the extremity. METHODS: A homogeneous group of 789 patients treated at a single institution between March 1983 and March 1999 with different protocols of neoadjuvant chemotherapy, with a minimum followup of 5 years, were retrospectively evaluated in relation to gender, age, serum levels of alkaline phosphatase, tumor site and size of the pathologic fracture, type of surgery, protocol of chemotherapy, surgical margins, and histologic response to preoperative treatment. RESULTS: The 5-year event-free survival (EFS) and overall survival rates were 60.1% and 67.5%, respectively. Upon univariate analysis, EFS was significantly related to the age of patients, serum value of alkaline phosphatase, tumor volume, histologic subtype, type of surgery, surgical margins, histologic response to preoperative treatment, and chemotherapy protocol. Local recurrences (4.8%) were significantly correlated with surgical margins. The 5-year post-recurrence EFS survival was 17% and was significantly lower for patients who had a local recurrence and metastases than for those with metastases only. Patients who had a recurrence only in the lung had a post-recurrence survival rate significantly better than others, correlated with the number of metastatic nodules and the length of the disease-free interval. CONCLUSIONS: Upon multivariate analysis, age < or = 14 years, high serum levels of alkaline phosphatase, tumor volume > 200 mL, a two-drug regimen chemotherapy, inadequate surgical margins, and poor histologic response to treatment maintained independent prognostic values on the outcome of nonmetastatic osteosarcoma of the extremities. These factors must be considered when deciding risk-adapted treatments for osteosarcoma patients.     

Intermediate results and functional evaluation of limb-salvage surgery for osteosarcoma: an intergroup study in Japan

This is a 2-7-year follow-up report by 21 institutes in Japan concerning limb-salvage surgery for osteosarcoma. Between 1980 and 1985, 248 patients with osteosarcoma were treated, and 105 patients had limb-salvage surgery. The percentage of cases treated by limb-salvage surgery increased with each year. The cumulative survival rate was 71% at 5 years in the limb-salvage group, and in the amputation group it was 46%; this indicates that cases for limb-salvage patients, tumor resection was classified this procedure. In limb-salvage patients, tumor resection was classified according to the surgical margin as intralesional excision, marginal excision, wide-with-marginal resection, wide resection, and radical resection. Wide resection was performed in most cases as the method of choice. Local recurrence was seen in 13 cases (12%). The overall functional evaluations by Enneking's system showed that the number of results rated excellent or good was relatively high in the early follow-up period, but this decreased later on, and cases rated fair or poor increased as the years passed. This was mainly due to postsurgical complications (44 cases). We identify a few problems in the functional evaluation system used now and suggest a reform of the system, so that physical and mental factors would be evaluated separately.     

AP化疗方案联合手术治疗原发性骨肉瘤的临床观察

目的探讨AP化疗方案联合手术治疗四肢原发性骨肉瘤的临床效果。方法回顾2008年1月至2011年11月,收治的四肢原发性骨肉瘤30例,病例资料及随访完整的20例患者纳人本研究,男12例,女8例;年龄9～38岁,平均19岁。发病部位：股骨远端10例,胫骨近端7例,肱骨近端3例。根据Enneking外科分期均为IIB期,术前穿刺活检病理亚型：成骨细胞型8例,成软骨细胞型6例,成纤维细胞型2例,小细胞性2例,毛细血管扩张型2例。20例患者均采用AP化疗方案联合手术治疗。结果随访时间12～55个月,平均35．6个月。20例中,保肢手术病例18例,截肢手术病例2例,手术即时保肢率为90％。7例因肺转移而死亡,其中5例死于术后2年内;2例分别在术后10、12个月复发,复发率为10％,末次随访时1例死亡,1例带瘤生存。Kaplan—Meier分析患者3年总生存率为66％。末次随访时规范化疗组12例中死亡3例,生存率为75％（9／12）;不规范化疗组8例中死亡4例,生存率为50％（4／8）。13例存活并保留肢体的患者末次随访时MSTS评分为23～27分,平均25．3分。结论AP化疗方案联合手术治疗四肢原发性骨肉瘤患者生存率和保肢率尚可,可以作为一种选择性应用的骨肉瘤化疗方案。     

Surgical outcomes and prognostic factors of non-metastatic radiation-induced sarcoma of bone

BackgroundThe survival and prognostic factors in non-metastatic, radiation-induced bone sarcomas of bone have not been described. Moreover, the quantitative data about surgical outcomes and complications after limb-salvage surgery versus amputation are quite limited.MethodsTwenty-five patients with non-metastatic, radiation-induced sarcoma of bone who underwent definitive surgery were analysed. Histological diagnosis was osteosarcoma in 19 and undifferentiated pleomorphic sarcoma in six. The definitive surgery was limb-salvage surgery in 15 patients and an amputation in 10.ResultsThe 5-year overall survival rate (OS) and the 5-year event-free survival rate (EFS) were 53% (95% CI 31%–70%) and 40% (21%–59%), respectively. Patients with wide or radical surgical margins (n = 13) showed significantly better OS compared with those with marginal (n = 8) or intralesional (n = 2) margins (5-year OS, radical or wide = 74%, marginal = 17%, intralesional = 0%, p = 0.044). The risk of local recurrence was significantly higher in the limb-salvage group compared to the amputation group (49% vs 0%, p = 0.011). OS and EFS were not significantly different between limb-salvage group and an amputation group (p = 0.188 and 0.912, respectively).ConclusionsWe believe non-metastatic, radiation-induced sarcoma of bone should be resected with the aim of achieving wide or radical margins. Although limb-salvage surgery was related to higher rates of local recurrence compared with those of the amputation group, OS and EFS were not different among two groups. Surgeons need to discuss the higher risk of local recurrence in limb-salvage surgery.     

Risk factors for local recurrences after limb-salvage surgery for high-grade osteosarcoma of the extremities

Background: Improvements in preoperative staging as well as in chemotherapeutic regimens have made limb-salvage surgery a reliable modality of treatment for high-grade osteosarcomas of the extremities, with local recurrences in most series of less than 10% after this type of surgery. The quality of surgical margins and local response to preoperative chemotherapy are known to be the most significant factors in recurrence [1, 8–10, 12], and complications related to the biopsy procedure may also be a significant factor. The study reported here comprised a histopathological analysis of our recurrent cases as part of an effort to identify the impact of each of the factors cited above.Materials and methods: Five hundred fourteen cases of high-grade, non-multicentric osteosarcoma of the extremities were treated at the Istituto Ortopedico Rizzoli between March 1983 and August 1991. In this study we analyzed 23 cases of local recurrence in patients with classic osteosarcoma who underwent limb-salvage procedures.Results: In 15 cases we found correlation between the site of local recurrence and the site where the margins were less than wide. In five cases the recurrence was secondary to complications of the biopsy procedure (hematoma, delayed healing). In one case we suspect a previously undetected skip lesion. In the remaining two cases no clear explanation was found for the recurrence. There was also a statistically significant difference in the time of appearance of recurrences related to the tumor response to chemotherapy.Conclusions: For only two cases of recurrence was there no clear explanation. In one we suspect an undetected skip metastasis, and in the other there were certain factors which may have increased its risk of recurrrence (non diagnostic trochar biopsy followed by an incisional biopsy, fair tumor necrosis, recurrence in a 'problem' anatomical site, i.e., the popliteal space). In the remaining cases the following factors were found to be directly related to the development of a local recurrence: a) the quality of the surgical margins, b) site of the biopsy as well as complications related to the biopsy procedure, c) local response to preoperative chemotherapy.     

新辅助化疗加保肢手术治疗肢体骨肉瘤

目的评价新辅助化疗加保肢手术治疗肢体骨肉瘤的临床疗效。方法选择1994年6月至2002年6月新辅助化疗加保肢手术治疗肢体骨肉瘤17例。达到广泛切除者11例，仅达边缘切除者6例；15例接受过术前化疗的病例切除标本均做多病理切片的坏死率评估。结果17例中无瘤生存超过5年的共有9例(52．9％)，其中截肢术2例(17．6％)，肢体功能评分结果，优7例、良2例、可3例、差5例，优良率为69．9％。结论新辅助化疗加保肢手术是治疗肢体骨肉瘤患者理想的治疗方法，术前有效化疗是保肢术成功的关键。     

Neoadjuvant treatment in osteosarcomas

The dismal prognosis of osteosarcoma of the limbs treated by amputation alone can be improved dramatically by including chemotherapy in an interdisciplinary regimen. Neoadjuvant chemotherapy is commonly used in order to eradicate the micrometastases and to prepare for limb-salvage surgery. To-days conservative surgery is possible in the majority of patients, including young children, and relapse-free survival attains 50-80%. High-dose methotrexate, doxorubicine, cis-platin and ifosfamide are considered the most active drugs against osteosarcoma. However, the best combination of drugs remains controversial with pending questions regarding the number of drugs to give for the preoperative phase of treatment and the value of salvage chemotherapy in poor histological responders. Furthermore long term toxicity of the drugs need to be better assessed. In order to answer these questions, treatment should be administered within the scope of prospective multi-centre trials.     

我国骨肉瘤治疗现状及改进建议——17家骨肿瘤治疗中心1998～2008年资料分析

目的收集17家国内著名的骨肉瘤治疗科室的近5～10年资料,反映我国骨肉瘤治疗现状,阐明促成建立多中心前瞻性研究共识的重要性。方法17家医院2015例骨肉瘤患者,男性58％,女性42％;10—30岁患者占70．7％;肿瘤侵袭膝关节的病例占80％;Ⅱa期病例占1．5％-39．0％,平均10．8％;Ⅱb期病例占54％～100％,平均83％;Ⅲ期病例占2％～15％,平均8％。新辅助化疗病例64．7％～100．0％,平均77．0％,辅助化疗病例8．0％～35．3％,平均18．0％;保肢手术病例50％-100％,平均79％;截肢手术病例3％～50％,平均21％。结果随访2年以上,总生存率（OS）37．5％～77．6％（平均64．0％）;总缓解率（OR）80．0％～94．5％（平均86．0％）;无病生存率（DFS）34．81％～69．7％（平均56．0％）;无复发生存率（RFS）32．2％-81．5％（平均60．0％）。保肢率79％;复发率0．8％～22．0％（平均9．1％）;肺转移率9．0％～42．5％（平均24．8％）。结论我国治疗骨肉瘤的现状显示多学科综合治疗已成为多家治疗中心的共识。建立多中心前瞻性临床治疗研究是需要迫切解决的问题,具体包括规范的诊断、外科分期、化疗药物的选择、化疗疗效的评价、有效的复查机制。     

Analysis of the efficacy and prognosis of limb-salvage surgery for osteosarcoma around the knee

Aim

Limb-salvage surgery has become the standard of care for extremity osteosarcoma. In this study, we investigated the survival and functional outcomes of patients with osteosarcoma around the knee who were treated with limb-salvage surgery.

Methods

We retrospectively reviewed the clinical data for 120 patients with osteosarcoma around the knee who were treated with limb-salvage surgery between 1998 and 2008. The sample included 75 males and 45 females. The mean age of the patients was 18.9 years. Osteosarcoma was diagnosed in the distal femur in 78 patients and in the proximal tibia in 42 patients. Statistical analyses were conducted to process and record the patient data and analyse the surgery's efficacy, prognosis and survival rates.

Results

All patients were followed for 6–144 months (mean of 56.8 months). The overall 5-year survival rate was 61.8%. Lung metastasis developed in 31 patients. Local recurrence developed in 9 patients. The average Musculoskeletal Tumor Society Score (MSTS) was 25.5 points on a 30-point scale. Sixteen patients underwent prosthesis revision and twelve patients underwent amputation. The overall survivorship of the prosthesis based on Kaplan–Meier estimates was 77% at five years and 71% at ten years. There was a higher incidence of extensor lag for the patients with osteosarcoma in the proximal tibia than for those with osteosarcoma in the distal femur (P < 0.01).

Conclusions

Treating osteosarcoma around the knee with limb-salvage surgery can preserve most of the knee's functionality. Attention must be paid to prevent the relatively high incidence of postoperative complications.     

Local and systemic control for osteosarcoma of the extremity treated with neoadjuvant chemotherapy and limb salvage surgery: the Rizzoli experience

Five-hundred and twenty-six patients with non-metastatic osteosarcoma of the extremities treated at Istituto Ortopedico Rizzoli from 1983 to 1995 with neoadjuvant chemotherapy and limb salvage, were retrospectively studied to evaluate the rate of local and systemic control. At a mean follow-up of 9.5 years (3-17), 320 patients remained continuously free of disease and 206 relapsed. The 5-year disease-free survival and overall survival were 64% and 70% respectively. In patients who relapsed, there were 31 local recurrences (6%). The rate of local failures was significantly higher in the 79 patients with inadequate surgical margins (marginal, intralesional, and contaminated margins) than in the 486 patients with wide surgical margins (2.6% vs. 25.0%; P<0.0001). Twenty-nine of the 31 patients (94%) with local recurrence also had metastases and died of the tumor. In comparison with patients who only had a systemic relapse, patients with local recurrences had a higher rate of metastases located in bones (41% vs. 7%; P<0.001), and a worse post-relapse outcome (5-year overall survival: 6% vs. 24%; P<0.04). We concluded that in osteosarcoma of the extremity treated with neoadjuvant chemotherapy: i) limb salvages procedures do not compromise the outcome of patients, provided the achievement of adequate surgical margins; ii) local recurrences are a marker either of the inadequacy of local treatment or of the high local and systemic aggressiveness of the tumor.     

Carboplatin and Doxorubicin in Treatment of PediatricOsteosarcoma: A 9-year Single Institute Experience in theNorthern Region of Thailand

Background: Osteosarcoma is the most common primary bone tumor in childhood and adolescence.Carboplatin, a platinum-derived agent, is used as neoadjuvant chemotherapy for pediatric osteosarcoma becauseof its anti-tumor activity and had low toxicity as compared to cisplatin. Objective: To determine demographic data,prognostic factors and outcome of childhood osteosarcoma treated with a carboplatin-based chemotherapeuticprotocol at Chiang Mai University. Method: A retrospective analysis was conducted on 34 osteosarcoma patientsaged less than 18 years and treated between 2003 and 2011. Results: Overall limb-salvage and amputation rateswere 23.5% and 70.6%, respectively. With the mean follow-up time of 29.5 months (1.5-108.9), the Kaplan-Meieranalysis for 3-year disease-free survival (DFS) and 3-year overall survival (OS) were 20.2±7.7% and 47.1±9.5%respectively. Patients who had initial pulmonary metastasis were at significantly greater risk for developingrecurrence (p=0.02, OR=7; 1.2-40.1) and had a tendency to have lower 3-year OS compared to those withoutinitial pulmonary metastasis (28.1±13%, 63.1±12.3%, respectively, p=0.202). On univariate analysis, age at diagnosis >14 years and patients who were declined surgery were significantly associated with lower 3-year OS (p=0.008 and <0.05, respectively). However, age at diagnosis, sex, tumor size and histological subtypes were not found to significantly affect recurrence or survival. Conclusions: In our study, the survival rate was far lower than those reported from developed countries. These might indicate the ineffectiveness of carboplatin in combination with doxorubicin as frontline treatment of pediatric osteosarcoma, especially in those with initial pulmonary metastasis.Refinement in risk and treatment stratification and dose intensification for pediatric osteosarcoma constitutes a future challenge to improve outcomes, especially in metastatic patients who may need a more intensive regimen.     

新辅助化疗结合保肢手术治疗肢体骨肉瘤

目的：评价新辅助化疗结合保肢手术治疗肢体骨肉瘤的临床疗效。方法：选择1995年1月-2003年1月新辅助化疗结合保肢手术治疗的肢体骨肉瘤31例。广泛切除22例，边缘切除9例。所有病例切除标本均做多病理切片的坏死率评估结果：随访2～8年，31例中无瘤生存超过5年19例（61.3％），肿瘤局部复发4例（12.9％）。肢体功能评估优良率为67．7％：结论：新辅助化疗结合保肢手术是治疗肢体骨肉瘤理想的治疗方法，术前有效化疗是保肢术成功的关键。     

95例ⅡB期肢体骨肉瘤生存分析—新辅助化疗结合区域动脉灌注疗效探讨

目的探讨术前新辅助化疗次数、区域动脉灌注化疗对骨肉瘤临床近期疗效及预后的影响。方法术前无远处转移的ⅡB期肢体骨肉瘤随访95例,随机分为新辅助化疗组和术后辅助化疗组。新辅助化疗组51例,其中加用动脉灌注化疗17例。新辅助化疗组术前化疗1．3个疗程,主要药物为MTX、DDP、IFO、EPI,动脉灌注化疗加用顺铂和表阿霉素灌注化疗1次。评价新辅助化疗组、术后辅助化疗组、新辅助化疗组中加用动脉灌注组间的疗效差异。结果随访满2年的79例患者中位生存期为53．0个月（95％CI18．08～87．92）,无病中位生存期为17．0个月（95％CI9．33～24．67）。新辅助化疗组的中位无病生存时间及中位生存时间均高于术后辅助化疗组,两组生存函数差异有统计学意义。加用灌注化疗的患者保肢率81．25％,远高于不加灌注化疗者,差异有统计学意义。结论新辅助化疗的实施提高了ⅡB期骨肉瘤患者的2年无病生存率及总生存率。是改善ⅡB期骨肉瘤患者预后的理想方法。动脉灌注化疗可以增加保肢几率,改善近期疗效,但对患者的远期生存影响无统计学意义。     

热化疗在保肢手术治疗下肢骨肉瘤中的应用

目的 研究术前肢体局部热化疗在手术治疗下肢骨肉瘤中的临床意义。方法 术前一周患肢注入化疗药物然后升温至41．8℃每次60—120rain。一周后行保肢手术治疗。结果 30例下肢骨肉瘤的患者在术前行局部热化疗后疼痛不同程度减轻，术中出血少，易切除并见瘤体缩小有坏死灶。结论 术前热化疗可以减轻患者疼痛，缩小肿瘤体积，有利于手术切除肿瘤，很大程度上保留肢体功能。     

肿瘤型假体机械性重建保肢手术治疗股骨远端骨肉瘤:单中心、回顾性早中期疗效分析

目的 探讨肿瘤型假体在股骨远端骨肉瘤保肢手术中的临床疗效.方法 对42例确诊为股骨远端骨肉瘤患者进行新辅助化疗及瘤段切除肿瘤型假体膝关节重建.结果 42例获15 - 55月(平均32月)随访.短期并发症发生率为11.9％,按Enneking功能评分系统,优19例,良21例,中等2例.2年无瘤生存32例;5年无瘤生存26例,4例带瘤生存,5年总生存率为71.4％.结论 对股骨远端骨肉瘤配合新辅助化疗行肿瘤广泛性切除,应用肿瘤型假体重建膝关节,取得较好的治疗效果.     

Telangiectatic osteosarcoma: the St. Jude Children's Research Hospital's experience

BACKGROUND: Telangiectatic osteosarcoma (TOS) is a rare subtype of osteosarcoma (OS). The authors reviewed their experience with TOS to characterize its histologic, radiologic, and clinical features. METHODS: The authors reviewed records, pathology material, and imaging studies from all patients with TOS who were treated between 1978 and 2005 and compared their outcomes with the outcomes of patients with all other subtypes of high-grade osteosarcoma (OS). RESULTS: Among 323 patients with OS, 22 patients (6.8%) had TOS. Two additional patients who were treated in Chile on a recent OS trial were included. The median age at diagnosis of the 24 patients was 15.7 years. Four patients (17%) had metastatic disease, and 9 of 21 patients (43%) had pathologic fractures. Only 5 patients (who were treated after 1994) underwent limb-salvage surgery. Estimates of 5-year event-free survival (58.3% +/- 11.9%) and overall survival (66.8% +/- 11.6%) were similar to those for patients with other OS subtypes (P > or = .85). The absence of local disease progression and chemotherapy with > or =3 agents that were active against OS were correlated with improved outcome (P < or = .005). The presence of a pathologic fracture was not associated with surgery type or patient outcome. CONCLUSIONS: TOS was associated with a high rate of pathologic fracture. With multimodality therapy, the outcome of patients with TOS was similar to that of patients with other high-grade OS subtypes. The absence of local disease progression and chemotherapy with > or =3 active agents were associated with a favorable outcome.     

软组织肉瘤动脉灌注新辅助化疗后的保肢治疗

目的探讨术前动脉内灌注化疗对软组织肉瘤的疗效及在保肢治疗中的意义。方法28例肢体软组织肉瘤,其中恶性纤维组织细胞瘤18例,滑膜肉瘤3例,脂肪肉瘤6例,原始神经外胚层肿瘤（PNET）1例。术前均给予选择性肿瘤供血动脉灌注化疗2-3周期,化疗药物为阿霉素／顺铂和异环磷酰胺。化疗后均行保肢手术治疗。结果28例术前化疗后均有疼痛缓解、皮温降低、肿胀减轻、瘤体不同程度缩小、边缘变清楚及关节活动度增加。化疗后均行肿瘤广泛切除术,术中获得良好的外科切除界限。随访6-46个月,平均25个月。2例死亡,1例局部复发行截肢术。术后12个月后采用MSTS93评分系统评分为24-29分,平均为27分。28例3年生存率为92.9％,初次保肢率100％,最终保肢率89.3％。结论肢体软组织肉瘤术前动脉灌注新辅助化疗是一种有效的保肢治疗方法。     

Preoperative cisplatin for initial treatment of limb osteosarcoma: its local effect and impact on prognosis

PURPOSE: The significance of preoperative cisplatin (CDDP) as a single agent has not been assessed in terms of its effect on prognosis. The purpose of this multi-institution study was to assess the local effect of preoperative CDDP as a single agent as well as its impact on the prognosis of limb osteosarcoma. PATIENTS AND METHODS: The study group comprised 44 patients with stage IIB limb osteosarcoma who were treated with single-agent CDDP as initial preoperative chemotherapy. Two to five courses of CDDP (mean 2.4 courses) were administered intravenously and/or intraarterially as an initial preoperative treatment. The mean dose of CDDP was 3.0 mg/kg (2.5-3.4 mg/kg). The effect of the treatment was evaluated clinically and histologically. RESULTS: The clinical and histological response rates to preoperative CDDP were 56.8% and 47.6%, respectively. The survival rate was 59.1% among all patients in the study, 64.0% among those with a grade III or IV clinical response, and 52.6% among those with a grade I or II clinical response, with no significant differences between the groups. The survival rate was 70% among patients with a grade III or IV histological response, and 54.5% among those with a grade I or II histological response, with no statistical differences between the groups. CONCLUSIONS: We consider that CDDP is a useful chemotherapeutic agent for preoperative induction therapy for osteosarcoma because of the excellent local effect observed. Good responders to preoperative CDDP showed a better survival rate, but a correlation between the local response to CDDP and the survival rate was not demonstrated statistically. Systemic multidrug chemotherapy should follow preoperative CDDP to diminish the microscopic foci of metastatic disease.