软组织肉瘤保存肢体的新技术应用

应用广泛切除术及高剂量率后装内照射新技术（Ｂｒａｃｈｙｔｈｅｒａｐｙ），治疗累及重要血管及神经的软组织肉瘤，达到控制预防局部复发，保存肢体功能的目的。５例肢体软组织肉瘤经治疗后均生存，随访未见局部复发及远处转移。作者介绍了保存肢体手术及肿瘤床１９２铱置管内照射的技术，同时建议对以往截肢指征应慎重考虑，只有在各种综合治疗失败情况下才考虑截肢。     

抑癌基因 P~(53)蛋白在78例软组织肉瘤的表达

本研究应用Ｐ５３蛋白单克隆抗体对７８例软组织肉瘤行免疫组化染色，并对各种软组织肉瘤组织中Ｐ５３蛋白的表达进行了分析研究，结果发现全部病例Ｐ５３总阳性率为４３．５％，在脂肪肉瘤（４７．０％）中阳性率较高，而平滑肌肉瘤（７．１４％）中阳性率较低。Ｐ５３蛋白阳性表达与肉瘤组织分化程度有关，分化愈低其阳性率愈高，且在不同类型肉瘤中有一定差别，说明Ｐ５３抑癌基因突变在软组织肉瘤发生发展过程中起着重要作用。     

Histological Changes in Recurrent Soft Tissue Sarcomas: Analysis of 56 Patients

Histological changes in 56 patients with recurrent soft tissuesarcomas (STS) were analysed. The original tumors included 23malignant fibrous histiocytomas, five liposarcomas, four leiomyosarcomas,four synovial sarcomas, four neurogenic sarcomas, four dermatofibrosarcomasand 12 other assorted tumor types. The histo-logical featuresof the recurrent tumors which underwent changes included increasedcellularity, an increased number of mitotic figures, extensionof sclerotic areas and the appearance of a storiform pattern;these were found in 30%, 43%, 41% and 29% of cases, respectively.No case showed a histological change from one subtype to another.A follow-up study revealed increased cellularity and mitoticcounts in the recurrent tumors to be signs of an unfavorableprognosis.     

Epidemiology of Soft Tissue Sarcomas in Karachi South,Pakistan (1995-7)

Introduction: The present study was conducted with the objective of examining epidemiological characteristicsof soft tissue sarcomas (STSs) in Karachi. Patients and methods: Epidemiological data of 96 (63 male and 33female) incident STS cases registered at Karachi Cancer Registry (KCR) for Karachi South (KS), from 1stJanuary 1995 to 31st December 1997, were reviewed. Results: The age standardized rate (ASR) world per100,000 were 3.3 (2.9%) and 2.1 (1.6%) in males and females, respectively, with mean ages of of 41.4 years (95%CI 35.77; 46.97) and 40.2 years (95% CI 31.27; 49.03). The age-specific curves showed a gradual increase in riskfrom the first until the eighth decade in both genders, with the highest peak at 75+ in females and 70-74 years inmales. In males, 8 (12.7%) STS cases were diagnosed in the pediatric age group (0-14), 12 (19.1%) in adolescentsand young adults (15-24 years), 19 (30.1%) in adults 25-49 years of age and 24 (38.1%) in the 50 years+ agegroup. In females the respective frequencies were 11%, 26%, 30% and 33%. The most common histologicaltumor was rhabdomyosarcoma, though the occurrence of the histological subtypes was age-dependent.Rhabdomyosarcomas and Ewing’s sarcomas were more frequent in children and adolescents whereasfibrosarcomas, leiomyosarcomas, liposarcomas, malignant fibrous histiocytomas (MFHs) and schwannomaswere encountered in the elderly. Conclusion: Karachi falls into a high risk region for STS, observed in a relativelyyounger population, with a male predominance, high frequency of rhabdomyosarcoma and advanced stage atdiagnosis. Information on grading and staging remain incomplete for most cases, which negatively affect diseasemanagement and survival.     

Retrospective Analysis of 498 Primary Soft Tissue Sarcomas in a Single Turkish Centre

Background: Soft tissue sarcomas (STS) must be managed with a team involving pathologists, radiologists,surgeons, radiation therapists and medical oncologists. Treatment modalities and demographic charasteristics ofTurkish STS were analysed in the current study. Material-Methods: Primary adult STS followed between 1999-2010 in Cukurova University Medical Faculty Department of Medical Oncology were analzied retrospectivelyResults: Of the total of 498 patients, 238 were male and 260 female. The most seen adult sarcomas wereleomyosarcoma (23%). Localization of disease was upper extremity (8.8%), lower extremity (24.7%), head-neck8.2%, thoracic 8%, retroperitoneal 5.6%, uterine 12.4%, abdominal 10%, pelvic region 3.6 and other regions10%. Some 13.1% were early stage, 10.2% locally advanced, 8.2% metastatic and 12.2% recurrent disease.Patients were treated with neoadjuvant/adjuvant (12%) or palliative chemotherapy (7.2%) and 11.4% patientsdid not receive chemotherapy. Surgery was performed as radical or conservative. The most preferred regimen wasMAID combination chemotherapy in the rate of 17.6%. The most common metastatic site was lung (18.1%). Theoverall survival was 45 months (95%CI 30-59), 36 months in men and 55 months in women, with no statisticallysignificant difference (p=0.5). The survival rates were not different between the group of adjuvant and palliativechemotherapy (respectively 28 versus 18 months) (p=0.06), but radical surgery at 37 months was better than22 months for conservative surgery (p=0.0001). No differences were evident for localization (p=0.152). Locallyadvanced group had higher overall survival rates (72 months) than other stages (p=0.0001). Conclusion: STScan be treated successfully with surgery, chemotherapy and radiotherapy. The survival rates of Turkish peoplewere higher in locally advanced group; these results show the importance of multimodality treatment approachand radical surgery.     

Pathology of Soft Tissue Sarcomas

Sarcomas are a rare, complex group of childhood and adult neoplasms with differentiation towards mesenchymal tissue, which may arise almost anywhere in the body. Although pathologically diverse, they frequently exhibit similar clinical presentations and radiological features. Correct histopathological diagnosis is therefore crucial, but there is overlap between histological patterns of malignant tumours, between benign and malignant lesions, and with non-mesenchymal tumours. Immunohistochemistry and molecular genetic techniques, the latter to detect tumour-specific alterations, add significantly to histological interpretation, but several groups of tumours still lack reliable immunohistochemical markers or reproducible genetic changes. The classification of sarcomas is incomplete and continues to evolve, and although the biology of many remains relatively poorly understood, our increasing insight into molecular events occurring in these tumours is certain to aid future diagnosis and therapy. This paper aims to give a broad overview of several of the main soft tissue sarcomas from a clinicopathological perspective, discussing laboratory diagnosis and the use and limitations of ancillary investigations, including recent developments in molecular diagnosis.     

Time dependent dynamics of wound complications after preoperative radiotherapy in Extremity Soft Tissue Sarcomas

AimsThe purpose of the study was to investigate the time dependent dynamics of wound complications and local control after preoperative radiotherapy (RT) in Extremity Soft Tissue Sarcomas (ESTS).Patients & methodsIn this retrospective cohort study, all patients treated for an extremity sarcoma with pre-operative radiotherapy followed by surgery were identified from a prospectively maintained database. A wound complication (WC) was defined as any local complication of the surgical area requiring intervention, hospital readmission or significant extension of the initial admission period.ResultsA total of 191 preoperatively irradiated ESTS patients were included in this study. WC was seen in 31% of the patients (n = 60). WC started after a median time of 25 days from surgery, with a median duration of 76 days. Adiposity, smoking and a lower extremity or superficial tumor localization were significantly correlated with an increased WC rate. Risk factors for a duration of WC ≥ 120 days are early development of WC (≤21 days after surgery) and smoking. Local control rates after 1, 3 and 5 years were 99%, 93% and 93%, respectively.ConclusionApproximately one-third of patients selected for preoperative RT develops a WC, typically in smoking, adipose patients with superficial tumor localizations in the lower extremity. Based upon the well-established superior long-term functional outcome, maintained excellent local control rates and the temporary nature of the WC issue, preoperative RT remains our preferred treatment. Although, in patients at high risk of WC, post-operative RT might be considered.     

软组织多形性细胞肉瘤标记特点研究

作者采用免疫组化技术对43例软组织多形性细胞肉瘤进行了多种抗体（α－AT、α－ACT、VM、DM、MG、S-100、SMA）标记，结果提示，除DM、MG及SMA对肌源性肿瘤有较大的特异性外，大多数抗体在不同组织类型的多形性细胞肉瘤中存在着交叉反应。作者认为，由于软组织肿瘤的多分化潜能，其组织类型的确定仍应主要依靠形态学特征，而免疫络化标记只能作为辅助的诊断依据。     

Frequent p53 Gene Mutations in Soft Tissue Sarcomas Arising in Burn Scar

Squamous cell carcinoma (SCC) is the commonest malignancy that arises in burn scars, which frequently contain p53 mutations. Soft tissue sarcoma (STS) also develops, though less frequently, in burn scars. p53 gene mutations were analyzed in paraffin-embedded specimens from 5 patients with STS (4 males and 1 female) that had arisen in a burn scar, by means of polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) followed by direct sequencing. Age at burn injury ranged from 2 to 10 (median 3) years, and STS developed with a latent period ranging from 29 to 79 (median 60) years. Histologically, all were malignant fibrous histiocytoma. The PCR-SSCP revealed aberrant bands in 4 (80%) of 5 cases. Direct sequencing revealed a total of 11 mutations in these 4 cases: 1 case had a single mutation, 1 had 2 mutations, and 2 had 4 mutations. Every tumor had at least 1 mutation that changed an amino acid, which may have provided the selection pressure for expansion. Thus, there is a high frequency of p53 gene mutations in STS appearing in burn scars. p53 mutations were also frequent in pyothorax-associated lymphoma (PAL), a lymphoma that develops in patients with long-standing pyothorax, so p53 mutations might be frequent in malignancies that develop in chronic inflammatory sites.     

Long-Term Treatment Results in Soft Tissue Sarcomas of the Thoracic Wall Treated with Pre-or-Postoperative Radiotherapy - a Single Institution Experience

Objective: To evaluate the long term results among patients with soft tissue sarcoma of the thoracic wall.Materials and Methods: Twenty-six patients who were treated with pre-or postoperative radiotherapy betweenDecember 1980-December 2007, with a diagnosis of soft tissue sarcoma of the thoracic wall were retrospectivelyevaluated. Results: The median age was 44 years (14-85 years) and 15 of them were male. A total of 50% ofpatients were grade 3. The most common histologic type of tumor was undifferentiated pleomorphic sarcoma(26.9%). Tumor size varied between 2-25 cm (median 6.5 cm). Seventeen of the cases had marginal and 9 hadwide local resection. Four cases received preoperative radiotherapy and 22 postoperative radiotherapy. Six ofthe patients with large and high grade tumors received chemotherapy. Median follow-up time was 82 months(9-309 months). Local recurrence and metastasis was detected in 34.6% and 42.3% of patients, respectively. Fiveyearlocal control (LC), disease-free survival (DFS), overall survival (OS), and disease-specific survival (DSS)were 62%, 38%, 69%, and 76% respectively. On univariate analysis, the patients with positive surgical marginshad a markedly lower 5-year LC rate than patients with negative surgical margin, but the difference was notsignificant (43% vs 78%, p=0.1). Five-year DFS (66% vs 17%) and DSS (92% vs 60%) rates were significantlyworse for the patients who had high grade tumors (p=0.01, p=0.008 respectively). Conclusions: Tumor gradeand surgical margin are essential parameters for determining the prognosis of thoracic wall soft tissue sarcomaboth in our series and the literature.     

软组织肉瘤局部切除加组织间照射治疗──附10例报告

１０例侵犯主要血管、神经和骨的肢体局部晚期软组织肉瘤，经局部切除加后装放射治疗并随访６～２４个月，除１例因肺、脑转移死亡，１例肺转移带瘤生存外，余８例均无局部复发或远处转移，仅１例切口延迟愈合。作者介绍了瘤床置管、后装（１９２）铱放射治疗的方法和注意事项，认为该法可有效控制局部晚期软组织肉瘤复发，并能较满意保留肢体功能。     

现代影像诊断学在累犯血管的软组织肉瘤外科治疗中的应用

目的:探讨现代影像学在软组织肉瘤累犯血管的诊断价值和对外科治疗的指导意义.方法:4例软组织肉瘤手术前、后均行影像学检查.结果:平均随访6个月,肿瘤无复发.现代影像学诊断血管被侵犯后的手术干预率为87.5%.结论:CT、MRI、DSA对诊断软组织肉瘤是否侵犯血管有重要价值,并能评价受累程度,从而指导外科治疗.     

Immunotherapy: A New (and Old) Approach to Treatment of Soft Tissue and Bone Sarcomas

Soft tissue and bone sarcomas are a rare and heterogeneous form of cancer. With standard of care treatment options including surgery, radiation, and chemotherapy, the long‐term survival is still low for high‐risk soft tissue sarcoma patients. New treatment strategies are needed. Immunotherapy offers a new potential treatment paradigm with great promise. Immunotherapy of soft tissue sarcomas dates back to Dr. Coley's first use of toxins in the late 1800s. A variety of strategies of immunotherapy have been tried in soft tissue and bone sarcomas, including various vaccines and cytokines, with limited success. Results of these early clinical trials with vaccines and cytokines were disappointing, but there are reasons to be optimistic. Recent advances, particularly with the use of adoptive T‐cell therapy and immune checkpoint inhibitors, have led to a resurgence of this field for all cancer patients. Clinical trials utilizing adoptive T‐cell therapy and immune checkpoint inhibitors in soft tissue and bone sarcomas are under way. This paper reviews the current state of evidence for the use of immunotherapy, as well as current immunotherapy strategies (vaccines, adopative T‐cell therapy, and immune checkpoint blockade), in soft tissue and bone sarcomas. By understanding the tumor microenviroment of sarcomas and how it relates to their immunoresponsiveness, better immunotherapy clinical trials can be designed, hopefully with improved outcomes for soft tissue and bone sarcoma patients.

Implications for Practice

Immunotherapy is a promising treatment paradigm that is gaining acceptance for the management of several cancers, including melanoma, renal cell carcinoma, prostate cancer, and lung cancer. There is a long history of immunotherapy in the treatment of soft tissue and bone sarcomas, although with little success. It is important to understand past failures to develop future immunotherapy treatment strategies with an improved possibility of success. This article reviews the history of and current state of immunotherapy research in the treatment of soft tissue and bone sarcomas, with particular regard to vaccine trials, adoptive T‐cell therapy, and immune checkpoint blockade.     

Fluorescence in Situ Hybridization (FISH) for Differential Diagnosis of Soft Tissue Sarcomas

Introduction:Soft tissue sarcomas are rare tumors comprising 1 percent of solid malignancies. The latest editionof WHO soft tissue pathology lists 94 benign and malignant soft tissue tumors. Many of these show a large degreeof morphological overlap. Immunohistochemistry has been shown to be reliable in many cases for differential diagnosisof lesions, although cytogenetic tests are considered the gold standard for many entities.Fluorescence in-situ hybridization(FISH) is a cytogenetic technique that uses fluorescent probes that bind to only those parts of the chromosome whichhave a high degree of sequence complementarity. Many soft tissue tumors show recurrent genetic mutations that arenow being used as diagnostic markers. Knowledge of the molecular identity allows prediction of behavior, prognosisand treatment response. Objective:The aim of this study was to identify genetic mutations in soft tissue sarcomas usingFISH testing and to assess correlations with histological diagnosis. Material and methods:A total of 25 cases of differentsoft tissue sarcomas diagnosed on histology with the help of immunohistochemical staining and for which FISH studieswere requested were included in this study. Three pathologists with a special interest in soft tissue sarcomas reviewedthe cases. FISH tests for EWS, the X:18 translocation, FOXO1 and MDM2 were respectively applied for 8 cases ofEwing sarcoma, 8 cases of synovial sarcoma, 2 cases of rhabdomyosarcoma and 7 cases of dedifferentiated liposarcomaand atypical lipomatous tumors/well differentiated liposarcomas. Results:EWS gene fusion was detected in 7 out of8 cases of Ewing sarcoma and the X:18 translocation was positive in 3 of the 8 cases of synovial sarcoma. FOXO1was not detected in either of the two rhabdomyosarcomas. MDM2 by FISH was detected in only one out of 5 cases ofatypical lipomatous tumors and 1 out of 2 dedifferentiated liposarcomas. Conclusion: FISH is a useful adjunct in thediagnostic assessment of different types of soft tissue sarcomas. It is easy to set up, is relatively inexpensive and hasthe ability to diagnose sarcomas with great accuracy, especially in cases which can not be accurately classified evenafter thorough histological and immunohistochemical evaluation. It may play a very important role in the accuratediagnosis and correct management of patients.