Imaging of chondrosarcomas.

Chondrosarcoma is the commonest primary sarcoma of bone in adults, with a male predominance. Patients are usually between 30 and 70 years old. Clinical symptoms are pain and tenderness with or without a mass, the average durationof symptoms being 1-2 years, but growth may be very slow, especially for pelvic tumours. Chondrosarcomas characteristically produce coalescent cartilage lobules of various size. The center often becomes necrotic or cystic.     

Clinical and histopathological prognostic factors in chondrosarcomas

Purpose. In an attempt to identify clinical and histopathological factors of prognostic importance in chondrosarcomas, 115 cases of malignant and borderline chondromatous tumours were reviewed.Patients/methods. Histopathological features tested for prognostic information as well as reproducibility included cellularity, nuclear pleomorphism, multinucleated cells, mitotic activity and grade. Eleven patients had a biopsy only, and a short survival (median 2.0 years); these were excluded from further analysis. The remaining 104 patients who had received intended curative treatment had a median survival of 14.7 years.Results. In univariate analysis, tumour size, extra-compartmental growth, surgical margin and sex were significantly correlated to recurrence-free survival (RFS); sex was marginally significant while age, site and pathological parameters were not significant. Overall survival (OAS) was likewise found to be independent of pathological features as well as site, size and surgical margin; but age, sex and extra-compartmental growth were statistically significant. However, when the same parameters were entered into a stepwise Cox (multivariate) analysis, only surgical margin, cellularity and pleomorphism were significantly related to RFS; margin, grade, pleomorphism and age to OAS. Overall inter-observer agreement on grade was relatively low: 0.54, with a Kappa value of 0.32. It was not better for the other histological parameters, with the exception of the mitotic count. However, acceptable values were achieved when the material was divided into low-grade (grade I and below) vs high-grade (grade II and III) lesions: overall agreement 0.79, Kappa 0.56.Discussion. Although the grading of chondrosarcomas is in need of improvement, its replacement by semiquantitative evaluation of individual histopathological parameters as performed in this study offers no advantage. Among the clinical parameters, only the adequacy of the surgical treatment and the patient's age appear to be important.     

Surgical treatment of skull base chondrosarcomas

Skull base chondrosarcomas are rare tumors and individual experience with their management is limited. We present a series of such tumors treated at our institution. Particular attention was paid to their extension pattern, choice of surgical approach, and outcome. Twenty-five patients were operated consecutively over a period of 19 years. Their clinical presentation, radiological features,surgical treatment, early and late treatment outcome, as well as survival rate were analyzed. The most frequent initial symptom was abducent palsy. The typical bone destruction of the petrous apex was found in 83%. Chondrosarcomas extended in 92% to the posterior cranial fossa. Total number of surgeries was 39. The operative approach was tailored to each case. The retrosigmoid approach was used in 30.8%, the pterional in 23%, and the transethmoid in 15.4%. Total tumor removal was achieved in 19 of the surgeries. New neurological deficits immediately after surgery appeared in 33.3%.     

Carbon ion radiotherapy of skull base chondrosarcomas

PURPOSE: To evaluate the effectiveness and toxicity of carbon ion radiotherapy in chondrosarcomas of the skull base. PATIENTS AND METHODS: Between November 1998 and September 2005, 54 patients with low-grade and intermediate-grade chondrosarcomas of the skull base have been treated with carbon ion radiation therapy (RT) using the raster scan technique at the Gesellschaft für Schwerionenforschung in Darmstadt, Germany. All patients had gross residual tumors after surgery. Median total dose was 60 CGE (weekly fractionation 7 x 3.0 CGE). All patients were followed prospectively in regular intervals after treatment. Local control and overall survival rates were calculated using the Kaplan-Meier method. Toxicity was assessed according to the Common Terminology Criteria (CTCAE v.3.0) and the Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) score. RESULTS: Median follow-up was 33 months (range, 3-84 months). Only 2 patients developed local recurrences. The actuarial local control rates were 96.2% and 89.8% at 3 and 4 years; overall survival was 98.2%at 5 years. Only 1 patient developed a mucositis CTCAE Grade 3; the remaining patients did not develop any acute toxicities >CTCAE Grade 2. Five patients developed minor late toxicities (RTOG/EORTC Grades 1-2), including bilateral cataract (n = 1), sensory hearing loss (n = 1), a reduction of growth hormone (n = 1), and asymptomatic radiation-induced white matter changes of the adjacent temporal lobe (n = 2). Grade 3 late toxicity occurred in 1 patient (1.9%) only. CONCLUSIONS: Carbon ion RT is an effective treatment for low- and intermediate-grade chondrosarcomas of the skull base offering high local control rates with low toxicity.     

Multiple chondrosarcomas in dyschondroplasia (Ollier's disease)

The relationship between dyschondroplasia (Ollier's Disease) and the possibility of malignant change is well known. The authors describe a patient who developed four primary chondrosarcomas over 11 years. These were treated by local wide excision and, in two sites, prosthetic replacement to preserve the limb. To the authors' knowledge, no patient with more than two primary chondrosarcomas has previously been described.     

Advanced chondrosarcomas: role of chemotherapy and survival

BackgroundThere are limited data about the role of chemotherapy in patients withadvanced chondrosarcomas.MethodsThe medical charts of 180 patients with advanced chondrosarcomas having received chemotherapy in 15 participating institutions between 1988 and 2011 were reviewed.ResultsMedian age was 52 years. Sixty-three percent of patients had conventional chondrosarcoma and 88% had metastatic disease. Combination chemotherapy was delivered in 98 cases (54.5%). One hundred and thirty-one patients (73%) received an anthracycline-containing regimen. Using RECIST, the objective response rate was significantly different according to histological subtype, being 31% for mesenchymal chondrosarcoma, 20.5% for dedifferentiated chondrosarcoma, 11.5% for conventional chondrosarcoma and 0% for clear-cell chondrosarcoma (P = 0.04). Median progression-free survival (PFS) was 4.7 months [95% confidence interval (CI) 3–6.5]. Performance status (PS) ≥2, number of metastatic sites ≥1 and single-agent regimen were independently associated with poor PFS. Median overall survival (OS) was 18 months (95% CI 14.5–21.6). PS, number of metastatic sites and palliative surgery were independently associated with OS.ConclusionsConventional chemotherapy have very limited efficacy in patients with advanced chondrosarcoma, the highest benefit being observed in mesenchymal and dedifferentiated chondrosarcoma. These data should be used as a reference for response and outcome in the assessment of investigational drugs in advanced chondrosarcoma.     

CyberKnife radiosurgery for the management of skull base and spinal chondrosarcomas

The use of CyberKnife (CK) stereotactic radiosurgery (SRS) for the management of central nervous system chondrosarcomas has not been previously reported. To evaluate outcomes of primary, recurrent, and metastatic chondrosarcomas of the skull base and spine treated with CK SRS, a retrospective observational study of 16 patients treated between 1996 and 2011 with CK SRS was performed using an IRB-approved database at Stanford University Medical Center. Twenty lesions (12 cranial, 8 spinal) across six males and ten females were analyzed. The median age at SRS was 51 years and median follow-up was 33 months. Median tumor volume was 11.0 cm³ and median marginal dosages were 22, 24, 26, 27, and 30 Gy for one to five fractionations, respectively. Overall Kaplan–Meier survival rates were 88, 88, 80, and 66 % at 1, 3, 5, and 10 years after initial presentation. Survival rates at 1, 3, and 5 years after CK were 81, 67, and 55 %, respectively. Actuarial tumor control was 41 ± 13 % at 60 months. At 36 months follow-up, tumor control was 80 % in primary lesions, 50 % in recurrent lesions, and 0.0 % in metastatic disease (p = 0.07). Tumor control was 58 % in cranial lesions and 38 % in spinal lesions. Radiation injury was reported in one patient. CK SRS appears to be a safe adjuvant therapy and offers moderate control for primary cranial chondrosarcoma lesions. There appears to be a clinically, albeit not statistically, significant trend towards poorer outcomes in similarly treated metastatic, recurrent, and spinal chondrosarcomas (p = 0.07). Lesions not candidates for single fraction SRS may be treated with hypofractionated SRS without increased risk for radiation necrosis.     

Stereotactic fractionated radiotherapy for chordomas and chondrosarcomas of the skull base

PURPOSE: To investigate the treatment outcome of patients suffering from skull base chordoma or chondrosarcoma after fractionated stereotactic radiotherapy. METHODS AND MATERIALS: We report 45 patients treated for chordoma or chondrosarcoma with postoperative fractionated stereotactic radiotherapy between 1990 and 1997. Patients had CT and MRI for 3D treatment planning performed under stereotactic guidance. Median dose at isocenter was 66.6 Gy for chordomas and 64.9 Gy for chondrosarcomas. MRI imaging was obtained in intervals after therapy to evaluate local relapse. Survival was calculated according to the Kaplan-Meier method. RESULTS: All chondrosarcomas had achieved and maintained local control and recurrence-free status at follow-up of 5 years. Local control rate of chordomas was 82% at 2 years and 50% at 5 years. Survival was 97% at 2 years and 82% at 5 years. At maximum follow-up of 8 years local control and survival rate of chordomas was 40% (82%). Clinically significant late toxicity developed in one patient. CONCLUSIONS: Our results demonstrate the feasibility of fractionated photon beam therapy and its success in the treatment of skull base tumors. Modern 3D treatment techniques provide superior results compared to conventional techniques. The role of high-precision radiotherapy compared to particle beam therapy in the treatment of these tumors is not yet fully clear and further research is needed.     

EXPRESSION OF THE MULTIDRUG RESISTANCE GENE IN LEUKEMIC CELLS

P-glycoprotein(Pgp; Mr=170,000) to encoded by a family of genes-Multldrug resistance gene. The Pgp has been demonstrated to mediate resistance to multiple structurally dissimilar drugs, which fuctions as an energy- dependent efflux pump so that a cell with high level of mdr expression can more effectively eliminate cytotoxic drugs. In this report, a simplified method for analysis of clinical samples and assess the level of gene expression was set up. Furthermore, by using 32P labelled mdr- 1 cDNA as the probe and RNA dot blotting the mdr-mRNAs from 5 cases of myeloblastic leukemia cells were analysed. It was shown that the level of mdr-1 expression In different myeloleukeic cells was various and reduced In one case after remission. The established method for mRNA analysis could be generalized for evaluating the level of mRNA in clinical samples.     

MTA1在鼻咽癌中的表达及意义

目的探讨MTA1在鼻咽癌中的表达及临床意义.方法应用逆转录-PCR（RT-PCR）技术,检测43例鼻咽癌组织和14例正常鼻咽部组织中MTA1 mRNA的表达. 结果 MTA1 mRNA 在鼻咽癌组织的平均表达水平明显高于鼻咽部正常组织（P〈0.05）.鼻咽癌组织中MTA1 mRNA高表达率与临床分期、T分期和N分期呈正相关关系.结论 MTA1基因过度表达与鼻咽癌浸润和转移密切相关.MTA1 mRNA的过度表达可能是评价鼻咽癌的恶性程度、转移的重要指标.     

Prognostic relevance of cell biologic and biochemical features in conventional chondrosarcomas

BACKGROUND: Conventional chondrosarcoma is the second most common malignant solid tumor of bone, and its management still poses a challenge for the orthopedic surgeon. Currently, tumor grade is the only parameter of prognostic significance besides stage and, possibly, resection margins. Additional independent prognostic markers therefore would be highly valuable for patient management. METHODS: In the current study, the authors evaluated biologic markers for various chondrocytic phenotypes by histochemical and immunohistochemical technology in a large series of clinically well defined cases of enchondromas and conventional chondrosarcomas, each with at least 5 years of clinical follow-up. RESULTS: The authors' results confirm the strong correlation between clinical behavior and cell differentiation as expressed by marker genes. The phenotypes of the tumor cells are the biologic substrate of the histopathologic appearance of the neoplasms and, thus, the biologic basis for classic tumor grading. Collagen Types II and X, as well as the proteoglycan aggrecan, suggest a mature neoplastic phenotype and good prognosis, i.e., low recurrence rate, rare metastasis, and long survival. Conversely, collagen Type I, together with cell spindling, indicates a transition to a more proliferative, so-called "dedifferentiated" phenotype, which clearly is associated with a poorer prognosis. The changes in cellular phenotypes are accompanied by changes in proliferative activity. Thus, low-grade neoplasms showing mainly mature and terminally differentiated (hypertrophic) chondrocytes display only scant proliferation whereas less differentiated chondrosarcomas with biologically dedifferentiated chondrocytes show significantly higher proliferative activity, a feature that is also highly correlated with prognosis. CONCLUSIONS: These data indicate that molecular markers are to a large extent the biologic basis of the conventional grading, rather than representing independent prognostic markers. The authors' results further indicate that COL1 has significant value in the distinction between enchondromas and low-grade chondrosarcomas including these that are histologically similar. Further understanding of chondrocytic phenotypes will be a promising way to provide new tumor markers for better understanding, diagnosis, and treatment of chondroid neoplasms.     

Radiotherapy for chordomas and low-grade chondrosarcomas of the skull base with carbon ions

PURPOSE: Compared to photon irradiation, carbon ions provide physical and biologic advantages that may be exploited in chordomas and chondrosarcomas. METHODS AND MATERIALS: Between August 1998 and December 2000, 37 patients with chordomas (n = 24) and chondrosarcomas (n = 13) were treated with carbon ion radiotherapy within a Phase I/II trial. Tumor conformal application of carbon ion beams was realized by intensity-controlled raster scanning with pulse-to-pulse energy variation. Three-dimensional treatment planning included biologic plan optimization. The median tumor dose was 60 GyE (GyE = Gy x relative biologic effectiveness). RESULTS: The mean follow-up was 13 months. The local control rate after 1 and 2 years was 96% and 90%, respectively. We observed 2 recurrences outside the gross tumor volume in patients with chordomas. Progression-free survival was 100% for chondrosarcomas and 83% for chordomas at 2 years. Partial remission after carbon ion radiotherapy was observed in 6 patients. Treatment toxicity was mild. CONCLUSION: These are the first data demonstrating the clinical feasibility, safety, and effectiveness of scanning beam delivery of ion beams in patients with skull base tumors. The preliminary results in patients with skull base chordomas and low-grade chondrosarcomas are encouraging, although the follow-up was too short to draw definite conclusions concerning outcome. In the absence of major toxicity, dose escalation might be considered.     

Dedifferentiated peripheral chondrosarcomas. A report of seven cases

Peripheral dedifferentiated chondrosarcoma (CS) is an exceedingly rare variant of the highly malignant entity of dedifferentiated chondrosarcoma. Only five such cases have previously been reported. Seven cases are analyzed and evaluated for the presentation and natural history of this highly malignant lesion when it arises in a tumor that was previously an osteochondroma. Both peripheral and central dedifferentiated chondrosarcomas are high-grade malignant lesions and require wide or radical surgical margins for adequate treatment. Despite adequate resection, survival is poor; five of the seven cases presented herein died of metastatic spread of their disease. These cases of the peripheral variant of dedifferentiated chondrosarcoma occurred in patients who were younger than patients with central dedifferentiated chondrosarcomas and may be present with longer duration of symptoms because they occur in previously long-standing benign osteochondromas. As such, they may be easily overlooked clinically and radiographically. Therefore, careful histologic analysis of all cartilage lesions arising on the surface of bone is essential to prevent overlooking foci of high-grade sarcomatous dedifferentiation.     

set基因在人结直肠腺癌中表达的研究

目的探究set基因在人类结直肠腺癌组织中的表达情况及其表达水平与临床病理特征之间的关系。方法 通过半定量PCR检测set基因在39例结直肠腺癌组织与自身对照的正常结直肠组织中的mRNA表达,免疫组织化学检测SET蛋白在9例结直肠腺癌患者癌组织及其自身对照的正常结直肠组织中的表达。结果 (1)set基因在26例结直肠腺癌组织中的mRNA表达水平高于其自身对照正常结直肠组织,占总数的66.7%的,其中6例患者set基因在结直肠腺癌组织中的表达水平是其在正常癌旁组织中表达水平的2倍以上,最高达22倍(P<0.05)。(2)免疫组织化学显示,SET蛋白在结肠腺癌和癌旁组织细胞核中均表达,其中8例患者的癌组织SET蛋白表达水平明显高于癌旁组织(P<0.05)。结论 set基因在结肠癌中的表达上调,可能与结直肠腺癌发病有关。