Prognostic factors of pulmonary metastasectomy for osteosarcomas of the extremities

Background: Factors affecting recurrence and survival after pulmonary resection for metastatic osteosarcomas are controversial. To confirm a role for resection of pulmonary metastases for such tumors, we herein reviewed our institutional experience. Methods: Between 1989 and 2007, 23 patients with pulmonary metastases from osteosarcomas of the extremities underwent pulmonary resection. Various perioperative variables were investigated retrospectively to confirm a role for metastasectomy and to analyze prognostic factors for overall survival and disease-free survival after metastasectomy. Results: Overall survival rate after metastasectomy was 31% at 5 years. Disease-free survival rate was 19% at 5 years after pulmonary resection. On multivariate analysis, patients with less than five pulmonary metastases and patients without pulmonary metastases identified during pre- and postoperative chemotherapy presented significantly favorable overall survival (p = 0.015 and 0.0082, respectively). Furthermore, the number of pulmonary metastases less than five was the only significantly favorable prognostic factor for disease-free survival on univariate analysis (p = 0.0055). Conclusions: Current practice of pulmonary metastasectomy for osteosarcomas in our institution was well justified. The number of pulmonary metastases more than five and the advent of pulmonary metastases during pre- and postoperative chemotherapy seemed relevant to a worse prognosis.     

Location of pulmonary metastasis in pediatric osteosarcoma is predictive of outcome

Background

The 3-year survival after pulmonary metastasectomy for osteosarcoma (OS) is approximately 30%. Resection of metastatic disease can prolong life in pediatric patients with OS. Our objective is to assess the outcome of pediatric patients with pulmonary metastases located centrally as compared with peripheral lesions.

Methods

A retrospective review of patients 0 to 21 years old with a diagnosis of OS with pulmonary metastases on computed tomographic scan between 1985 and 2000 was completed. Demographics, metastasis location, survival, morbidity, and mortality were evaluated.

Results

Of 115 patients who had pulmonary metastasis secondary to OS, there were 96 wedge resections and 13 lobectomy/pneumonectomies in 84 patients. The morbidity of wedge resection was 9% and lobectomy/pneumonectomy was 8%. There were no deaths from surgery. The median survival for patients undergoing lobectomy compared with wedge resection was 0.61 and 1.14 years, respectively, but did not reach statistical significance. The median overall survival for the entire cohort was 0.75 years. The median overall survival after initial detection of metastatic disease was 1.06 years among the patients with peripheral disease, compared with 0.38 years in patients with central disease (P = .008).

Conclusion

Patients with central pulmonary metastases in OS have a very poor prognosis, even after operative treatment, compared with those with peripheral disease. Patients with central lesions may benefit from other nonsurgical treatment options.     

The optimal timing to resect pulmonary metastasis

OBJECTIVE: There is no criterion for the timing of surgical resection of pulmonary metastasis. In this study, we investigated the optimal period for pulmonary metastasectomy. METHODS: Between 2000 and 2005, 68 patients underwent complete pulmonary resection of metastatic cancer. Clinical prognostic factor in multivariate analysis was examined. RESULTS: The interval from pulmonary metastasectomy until subsequent recurrence and the interval from detection of pulmonary metastasis until pulmonary metastasectomy were independent prognostic factors. To investigate the relationship between the two characteristics, the 68 patients were divided into two groups according to the interval from lung metastasectomy until subsequent recurrence. Nineteen patients relapsed within 1 year after pulmonary metastasectomy (group A), while 49 patients did not relapse within 1 year (group B). The interval from detection of pulmonary metastasis until pulmonary metastasectomy was significantly shorter in group A than in group B (2.9 months vs 7.1 months, p=0.01). Based on these results, we divided the patients into two different groups and survival was compared. Significantly shorter survival was observed in the patients who underwent pulmonary metastasectomy within 3 months after detection of pulmonary metastasis (group X, n=35) than in those who underwent the surgery beyond 3 months (group Y, n=33). CONCLUSIONS: There were many cases of early relapse after metastasectomy when the interval from detection of pulmonary metastasis until pulmonary metastasectomy was short. Performing metastasectomy at least three months after detection of pulmonary metastasis may significantly improve the prognosis of patients.     

Role of metastasectomy for liver metastasis in stage IV anal cancer

IntroductionThere is a paucity of data on the role of metastasectomy for metastatic anal cancer on survival outcomes. We aim to define the role of metastasectomy in stage IV anal cancer.MethodsNational Cancer Database (NCDB) from 2004 to 2014 was accessed to include patients with metastatic anal cancer, excluding adenocarcinoma, neuroendocrine, and ‘other’ histologies. We compared patients undergoing metastasectomy (n = 165) to those who did not have metastasectomy (n = 2093) by age, sex, cancer grade, and site of metastasis, including metastasis to bone, liver, and lung, using chi-square analysis. The primary outcome was overall survival.ResultsPatients had equal distribution of metastatic sites between those who underwent metastasectomy versus no metastasectomy: bone (7.64% vs 4.85%, p = 0.22), brain (0.24% vs 0%, p = 1.0), liver (23.22% vs 29.70%, p = 0.07), and lung (11.85% vs 9.09%, p = 0.38). Survival following metastasectomy was increased at one year (71% vs. 61%, p = 0.016), two years (50% vs. 38%, p = 0.014), and five years (30% vs. 19%, p = 0.025). Median overall survival was increased (23 months vs. 16 months; p = 0.015) for patients with metastasectomy. Survival increases were demonstrated only in the group with liver metastasis undergoing metastasectomy. When stratifying for liver metastases only, median overall survival time was further increased (34 months vs. 16 months; p < 0.0001) following metastasectomy.ConclusionThese results demonstrate a survival benefit for hepatic metastasectomy in stage IV anal cancer. Our findings demonstrate a potential survival benefit in highly select patients with metastatic anal cancer to the liver. These findings support further investigation in a randomized clinical trial to delineate these findings.     

Surgical management and outcome of osteosarcoma patients with unilateral pulmonary metastases

Purpose

The surgical management of osteosarcoma patients with unilateral pulmonary nodules is controversial. The authors reviewed their institutional experience to evaluate the incidence of occult contralateral metastases.

Methods

Data were obtained retrospectively on all consecutive osteosarcoma patients from 1980 to 2002. Eighty-four patients with pulmonary nodules were identified. Forty-one had bilateral disease, and 43 had unilateral involvement by computed tomography (CT) scan.

Results

All 43 patients with unilateral nodules underwent ipsilateral thoracotomies. Fifteen patients had negative exploration findings, and only 1 had pulmonary relapse. Of the 28 patients with metastases confirmed at initial thoracotomies, 14 had extensive pleural or extrapulmonary disease at initial thoracotomy followed by disease progression. The other 14 are separated into early versus late metastases, using 2 years from diagnosis as the cutoff point. Seven of the 9 (78%) patients with early metastases had or subsequently had contralateral disease; 6 were identified at staged contralateral thoracotomy and 1 had relapsed in the unexplored lung a year later. Only 1 of the 5 patients with late unilateral metastases had relapse in the contralateral side.

Conclusions

Our data indicate that there is a high rate of contralateral involvement in osteosarcoma patients with unilateral nodules diagnosed by CT scan. Staged bilateral thoracotomies should be considered in osteosarcoma patients presenting with unilateral pulmonary disease on imaging studies within 2 years of diagnosis.     

骨肉瘤p－糖蛋白表达水平与肺转移

目的 研究骨肉瘤多药耐药性的表达与预后，证实ｐ－糖蛋白（ｐ－ｇｐ）介导骨肉瘤的ＭＤＲ现象，明确ｐ－ｇｐ表达与一年肺转移的关系。方法 采用免疫组化ＬＳＡＢ法，检测８４例骨肉瘤中ｐ－ｇｐ表达，半定量化计量ｐ－ｇｐ的着色强度及阳笥率，通过多因素相关分析和生存分析，探讨骨肉瘤预后的相关因素和高危因素。结果 （１）８４例骨肉瘤ｐ－ｇｐ表达阳性５５．１％，其中以低表达为主，占６５．２％，高表达占３４．８％；（     

99例骨肉瘤肺转移患者随访结果分析

目的 了解骨肉瘤肺转移的预后情况,分析影响预后的因素.方法 回顾2000年1月至2008年7月治疗的99例骨肉瘤肺转移患者的临床资料,并对其预后进行随访,随访时间13～91个月,平均24.45个月.其中男65例,女34例;确诊时年龄7～68岁,平均20.39岁.患者均接受原发部位肿瘤切除治疗,93例患者接受新辅助化疗,6例因经济原因而未行其他辅助治疗.16例患者在就诊时即存在肺转移;47例在接受治疗期间发现肺转移,36例在随访期间发生肺转移.就发病年龄、肺转移数目、肺转移发生时段、合并其他部位的转移、原发肿瘤对化疗的反应、肺转移治疗等有可能影响预后的因素进行统计学分析.结果 从确诊骨肉瘤到发现肺转移时间为0～74个月,平均9.05个月.患者确诊骨肉瘤后的中位生存时间为25个月;累计一年、两年及五年生存率分别为87.4%、56.8%、23.4%.单因素统计分析显示骨肉瘤肺转移影响生存的有效预后因素为肺转移发生的时段及针对肺转移病灶的治疗;多因素统计分析显示肺转移发生的时段是影响预后的独立因素.其他因素如发病年龄、肺转移数目、合并其他部位的转移、原发肿瘤对化疗的反应等不具有统计学意义.结论 转移发生较晚且积极干预的骨肉瘤患者可获得较好的预后.对肺转移瘤进行积极的手术切除和辅助化疗能有效延长骨肉瘤肺转移患者的生存时间.     

43例骨肉瘤患者预后的多因素分析

目的：探讨影响骨肉瘤患者预后的相关因素。方法：回顾性分析2005年3月至2007年3月手术治疗并经病理证实的43例骨肉瘤患者的临床资料,包括性别、年龄、部位、病程、化疗前血清碱性磷酸酶水平、术前化疗、En-neking分期、手术方式及远处转移情况等9项相关因素,采用Kaplan-Meier法计算生存率,应用Log-rank检验行单因素分析,COX检验行多因素分析,研究这些因素与骨肉瘤患者3年生存率之间的关系。采用精确概率Fisher检验研究化疗疗效对骨肉瘤患者预后的影响。结果：43例均获随访,28例存活,15例死亡,生存时间6～65个月,平均39.7个月,中位生存时间42个月,3年总生存率65.1%。单因素分析显示,骨肉瘤预后与部位（P=0.010）、Enneking分期（P=0.002）、手术方式（P=0.000）、远处转移（P=0.002）有相关性;COX多因素分析显示Enneking分期（P=0.028）、手术方式（P=0.001）及远处转移（P=0.007）是影响骨肉瘤患者预后的独立因素。Fisher精确检验显示,尽管术前是否行新辅助化疗对预后影响不明显,但是新辅助化疗疗效的好坏是患者预后的重要影响因素（P=0.007）。结论：骨肉瘤预后与En-neking分期、手术方式及远处转移密切相关,早期发现及充分切除肿瘤是提高骨肉瘤预后可干预措施。     

40~60岁肢体骨肉瘤病人的临床治疗效果与策略

目的 分析40~60岁肢体骨肉瘤病人的临床治疗疗效,总结预后相关因素并探讨治疗策略。方法 回顾性分析2002年4月至2015年10月国内7家骨肉瘤治疗中心收治的确诊为肢体骨肉瘤的62例病人的资料,其中男34例,女28例;年龄范围限定在40~60岁,平均年龄为50.4岁;收集病人一般情况、发病部位、术前穿刺、化疗情况、手术方式、复发转移及生存情况等。以上述因素为变量指标,应用Kaplan-meier法测算生存率,研究这些因素与3年、5年生存率之间的关系。结果 62例肢体骨肉瘤病人中发病于膝关节周围者50例,约占80.6%。62例病人均得到随访,随访12~115个月,平均随访时间为43个月;3年和5年总生存率为80.6％、56.5%;3年和5年无瘤生存率为41.9%、32.3%;5年总生存率：术前化疗组与未化疗组分别为51.5%、62.1%;术后化疗组与未化疗组分别为52.1%、71.4%;术前术后均化疗组与均未化疗组为51.6%,61.3%;保肢手术组和截肢手术组分别为57.1%、53.8%。术后无复发转移、单纯复发、肺转移、多发转移的病人3年生存率分别为89.7%、78.6%、50.0%、73.3%。结论 40~60岁肢体骨肉瘤病人,膝关节周围发病率高于年轻病人,且预后较差,其预后与术前穿刺明确诊断、术后复发转移情况密切相关,其临床治疗应当建立在充分切除肿瘤的基础之上,严格遵照Enneking外科分期,降低肿瘤的复发转移率,以期改善预后。     

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。     

成人骨肉瘤的临床特点及预后影响因素

目的 分析成人骨肉瘤患者的临床与治疗特点,探讨预后相关因素.方法 回顾性总结2003年3月至2005年3月间收治并确诊为骨肉瘤的30例40岁以上成年患者的病例资料,以性别、年龄、肿瘤生长部位、肿瘤大小、血清碱性磷酸酶水平、影像学表现、病理骨折、组织学分级、术前诊断正确性、Enneking外科分期、手术方式、化疗、远处转移13项因素为变量指标,应用Kaplan-Meier法测算生存率,应用Los-rank检验行单因素分析,应用Cox回归模型行多因素分析,检验研究这些因素与3年生存率之间的关系.结果 所有30例患者均得到随访,存活17例,随访时间36～60个月,平均41个月;死亡13例,死亡时间为术后3～35个月,平均16个月,3年生存率56.7%.30例患者中四肢骨20例,中轴骨lO例;血清碱性磷酸酶水平22例正常,8例升高;影像学表现溶骨型17例,混合型8例,成骨型5例.3年生存率与年龄、肿瘤生长部位、血清AKP水平、Enneking外科分期、手术方式、远处转移相关(单因素P值<0.05),其中仅手术方式为独立相关影响因素(多因素P值<0.05),而与性别、肿瘤大小、影像学表现、病理骨折、组织学分级、化疗及术前诊断正确性无相关关系(P>0.05).结论 成人骨肉瘤临床表现较年轻患者更好发于中轴骨,血清AKP水平多正常,影像学多见溶骨型改变.其预后与手术方式密切相关.成人骨肉瘤的治疗应当建立在充分切除肿瘤的基础上,以期改善预后.     

Prognostic effects of doctor-associated diagnostic delays in osteosarcoma

Introduction  In this retrospective study, we evaluated to what extent diagnostic delays impact prognosis in osteosarcoma. Materials and methods  The authors identified 26 osteosarcoma patients who had undergone inappropriate procedure-associated diagnostic delays of more than 45 days after surgery, calculated overall survival rates, and analyzed clinicopathologic characteristics. Results  Initial clinical impressions were of a benign bone tumor in 15 patients, fracture in 8, and infection in 3. After initial inappropriate procedures, primary surgeons failed to send a tissue sample to a pathologist for definite diagnosis in 12 cases, and pathologists made incorrect diagnoses in the other 14. The average doctor-associated diagnostic delay after inappropriate surgery for these 26 patients was 10.5 months. Following referral to our institute, 22 underwent both surgery and chemotherapy and the remaining 4 patients underwent chemotherapy only. Four of the 26 patients were alive at last follow-ups. Estimated 5- and 10-year overall survival rates were 26 and 10%, respectively. Conclusions  The present study shows that doctor-associated diagnostic delay superimposed on an inappropriate primary procedure has a significant detrimental effect on overall survival in osteosarcoma. This study demonstrates that surgeons and pathologists should spare no effort to minimize diagnostic errors and delays.     

骨肉瘤预后个体化预测模型列线图的建立

 目的 通过对骨肉瘤患者的临床、病理学、影像学及随访资料进行预后因素分析,建立骨肉瘤预后预测模型列线图,并验证其准确度。方法 收集1998至2008年确诊且符合入组标准的235例骨肉瘤患者组成建模组,2009年的55例骨肉瘤患者组成验证组。单因素生存分析采用Kaplan-Meier法绘制生存曲线,Log-rank法进行统计学分析;应用Cox比例风险模型进行多因素分析,确定独立预后因子;然后应用R软件建立预测模型列线图,内部验证运用Bootstrap法,外部验证运用验证组,一致性指数（C-index）用来评价模型准确度,并绘制出列线图预测和实际观察的五年生存率校准曲线。结果 建模组和验证组五年总体生存率分别为46.1%±6.7%和61.8% ±12.9%。多因素分析结果显示,病理性骨折、入院时碱性磷酸酶水平、肿瘤大小、肿瘤分期和术后化疗次数是独立预后因素。校准曲线显示列线图预测与实际观察的五年生存率有很好的一致性。列线图预测五年生存率的C-index为0.74（95%CI,0.70~0.78）,明显高于Enneking分期系统。应用验证组进行外部验证,列线图、Enneking分期和美国癌症联合委员会（AJCC）分期系统的C-index分别为0.71、0.54和0.56,提示列线图比Enneking分期及AJCC分期的预后预测准确性更高。结论 成功建立的预测骨肉瘤患者总体生存列线图能实现个体化预测,且与其他预后预测系统相比更直观、准确。     

Growth patterns of osteosarcoma predict patient survival

Introduction  In this retrospective study, we assessed tumor growth patterns as visualized on MR images, and examined whether tumor growth patterns correlate with clinicopathologic variables. In addition, we also evaluated the relationship between patient outcome and tumor growth pattern in the whole study cohort and in subsets of AJCC IIA and IIB patients. Materials and methods  We retrospectively reviewed 347 patients with Enneking stage IIB and AJCC stage II osteosarcoma that was treated with surgery and neoadjuvant chemotherapy at our institute. Patients were divided into three groups based on tumor growth pattern, namely, concentric, eccentric, and longitudinal groups. Fisher’s exact test was performed to analyze correlations between tumor growth patterns and clinicopathological variables. Five-year metastasis-free survival and overall survival were evaluated using univariate and multivariate analyses. Results  In terms of tumor growth patterns, 225 patients (64.8%) had a concentric, 71 (20.5%) an eccentric and 51 (14.7%) a longitudinal tumor. Eccentric tumors were usually small and responded well to chemotherapy, whereas concentric tumors were large and responded poorly. The prognostic significances of tumor growth patterns were confirmed by univariate and multivariate analyses. Among AJCC stage IIA patients, no survival difference was found according to growth pattern, whereas in AJCC stage IIB patients, longitudinal tumors were associated with significantly better survival than concentric tumors. Conclusions  Tumor growth pattern was found to be an independent prognostic factor in stage II osteosarcoma. Moreover, longitudinally growing tumors were associated with better survival in AJCC stage IIB patients. Our results suggest that tumor growth pattern could be used as an indicator of risk-adapted therapy when combined with other prognostic factors. Each author certifies that his institution has approved or waived approval for the human protocol for their investigation, and that all investigations conformed to the ethical principles of research.     

Isolated subcutaneous metastasis of osteosarcoma 5 years after initial diagnosis

The pediatric malignancies most likely to metastasize to the skin are neuroblastoma, leukemia, and rhabdomyosarcoma. Cutaneous and subcutaneous metastases from osteosarcoma are extremely rare, with only a few cases reported in pediatric patients with multifocal synchronous osteosarcoma. We describe the case of a 19-year-old woman with a single subcutaneous nodule of the abdominal wall that, on histologic evaluation, proved to be a metastatic high-grade osteosarcoma 5 years after her initial diagnosis.     

骶骨原发骨肉瘤的外科治疗效果评价

目的:评价骶骨原发骨肉瘤的外科治疗效果。方法:回顾性分析2000年6月~2013年12月在我院接受肿瘤切除重建手术的26例骶骨原发骨肉瘤患者资料。其中男15例,女11例;中位年龄28岁(12~68岁)。分析本组患者的手术方式、总体与无进展生存时间以及功能状态。采用卡方检验比较整块切除和分块切除术后复发率。Kaplan-Meier法计算总体生存率,比较整块切除和分块切除组的总体生存率及无进展生存率。结果:16例患者接受整块切除术,10例接受分块切除术。出血量3435.3±1529.0ml(400~6600ml),手术时间6.8±2.4h(3~12h)。无围手术期致死性并发症发生。8例(30.7%)出现伤口并发症,经再次手术治疗后愈合良好。3例保留至少单侧S3及以上神经根的患者,术后大小便功能基本正常;7例保留至少单侧S2及以上神经根的患者中,术后膀胱控尿功能及大便控制部分受损,但均可自行排尿排便;仅保留至少单侧S1以上神经根的6例患者,术后均留置尿管,行自主膀胱功能锻炼,半年后均可拔除尿管,经定时挤压腹部排尿,此类患者均有不同程度的大便困难,但未做结肠造瘘。9例行全骶骨切除的患者均切断双侧S1神经根,5例患者术后出现足的跖屈肌力减弱,但可借助双拐或支具下地行走。术后随访6~87个月(29.7±19.7个月)。13例(50%)患者术后出现远处转移,10例患者(38.5%)出现局部复发(其中5例为局部复发合并远处转移)。术后1年生存率为92.3%,5年生存率为38.7%。整块切除者复发率为3/16(18.8%),分块切除者复发率为7/10(70%),分块切除复发率较整块切除高(P=0.015)。中位生存时间整块切除者为24个月,分块切除者为18个月,总体生存率无统计学差异(P=0.22);中位无进展生存时间整块切除者为19个月,分块切除者为8个月,整块切除者的无进展生存率高于分块切除者(P=0.04)。结论:对于骶骨原发骨肉瘤,整块切除术的局部控制率及无进展生存率优于分块切除术;部分病例可获得长期生存,但5年整体生存率仍较低。     

Use of radiotracer labeling of pulmonary nodules to facilitate excisional biopsy and metastasectomy in children with solid tumors

Purpose

Excision of suspected pulmonary metastases in children is challenging in the setting of multiple nodules or nodules that are small, deep, or soft. This study describes preoperative technetium macro-aggregated albumin (Tc 99m MAA) localization of pulmonary lesions to aid in intraoperative identification and resection.

Appearance of lung metastasis from osteosarcoma 21 years after initial treatment

This report describes a case of metastasis to the lung 21 years after the initial treatment of primary osteosarcoma in a 79-year-old man. The osteosarcoma was in the right femur and had resulted in amputation. The patient presented with painless hematuria, and a workup revealed a squamous cell carcinoma of the urinary bladder with invasion into the perivesicular fat. The patient received radiation therapy. Follow-up computed tomography of the chest revealed a nodule measuring 21 × 14 mm in the right upper lobe of the lung. Repeated transbronchial lung biopsies and needle biopsies were unsuccessful, so wedge resection of the right upper nodule was performed by video-assisted thoracic surgery to obtain a definitive diagnosis. The final pathological diagnosis was consistent with metastasis from the primary osteosarcoma removed 21 years earlier.     

Popliteal lymph node metastasis of tibial osteoblastic osteosarcoma

INTRODUCTION

We report a case with lymph node metastasis of osteosarcoma, which is a rare entity in comparison to hematogeneous lung or bone metastasis.

PRESENTATION OF CASE

Twenty-seven years old male patient referred to our clinic complaining of ongoing left knee pain and swelling since one month without a history of prior trauma. Magnetic resonance imaging (MRI) revealed a mass of malignant nature which causes more prominent expansion and destruction of the bone distally with periosteal reaction. A lymphadenomegaly 16 mm × 13 mm in diameter was also present in the popliteal fossa having the same signal pattern with the primary lesion. Thirteen weeks following the first referral of the patient, wide resection and reconstruction with modular tumor prosthesis was performed. Popliteal lymph node was excised through the same incision. Pathologic examination of the resected speciman reported osteoblastic osteosarcoma. The lymph node extirpated from the popliteal fossa was reported to be a metastasis of the primary tumor.

DISCUSSION

Osteosarcoma of the long bones is the most common primary malignant bone neoplasm of both childhood and adulthood. Osteosarcomas commonly metastasize hematogeneously to the lungs and bones. Lymph node metastasis is a rare entity. Similar studies report rates between 2.3% and 4%. It is not clearly explained, how lymph node metastasis in osteosarcoma occurs despite lack of lymphatic drainage in normal cortical and spongious bone.

CONCLUSION

Lymph node metastasis of osteosarcoma is a rare entity and metastatic patterns could not be clearly explained. On the other hand, the effects of lymph node metastasis on prognosis are also not clearly defined and further studies are needed.     

基于生物信息学分析骨肉瘤肺转移的关键基因和功能鉴定

目的：采用生物信息学的方法筛选骨肉瘤肺转移的差异表达基因,并探讨其功能及调控网络。方法：从GEO 数据库 (http://www.ncbi.nlm.nih.gov/gds) 中筛选数据集 GSE14359, 使用 GEO2R 在线工具筛选差异表达基因(differentially expressed gene,DEG);在线 HMMD 数据库(http://www.cuilab.cn/hmdd)下载骨肉瘤疾病相关的 miRNA,FunRich 软件预测靶基因,与 DEG 取交集,获得目标基因;根据靶向关系形成 miRNA-mRNA 关系对,数据导入 Cy-toscape 可视化;DAVID 对目标基因行 GO 和 KEGG 通路富集分析;STRING 构建 PPI 网络,Cytoscape 可视化,Cyto-Hubba 插件筛选中枢基因,在线网站进行表达和生存分析。结果：共鉴定出 704 个 DEG,由 477 个上调基因和 227 个下调基因组成。FunRich 预测出 mRNA 7 888 个,两者交集,获得目标基因 343 个。KEGG 富集分析显示:目标基因主要参与焦点粘连、细胞外基质(extracellularmatrix,ECM)受体相互作用、肿瘤坏死因子(trmor necrosis factor,TNF)信号通路、PI3K-Akt 信号通路、白细胞介素-17(interleukin 17,IL-17)信号通路、MAPK 信号通路。获得 10 个中枢基因(CC-NB1、CHEK1、AURKA、DTL、RRM2、MELK、CEP55、FEN1、KPNA2、TYMS),CCNB1、DTL、MELK 和预后不良高度相关。结论：该研究确定的关键基因和功能通路可能有助于了解骨肉瘤肺转移癌发生和进展的分子机制,并提供潜在的治疗靶点。