59例软组织肉瘤的MRI特征与组织病理分级的关系

背景与目的:软组织肉瘤的边缘部生长方式是影响肿瘤局部复发、转移的重要影响因子。本研究采用MRI检查探讨软组织肉瘤边缘表现与肿瘤病理分级之间的相关关系,以便在术前能对软组织肉瘤的生物学特性进行评估。方法:对59例软组织肉瘤患者进行MRI检查,应用自旋回波(SE)序列,采集T1加权(T1W)、T2加权(T2W)图像。在MRI图像上对软组织肉瘤的肿瘤边界、T2W图像上瘤周高信号征象、瘤周低信号包膜征象进行分析。59例软组织肉瘤均经手术病理证实,根据组织切片表现对软组织肉瘤进行病理分级。结果:软组织肉瘤的病理分级与肿瘤边界的清晰程度有关(P<0.05),60.0%Ⅰ级肿瘤其边界清晰,而60.0%Ⅲ级肿瘤其边界不清楚。Ⅱ级与Ⅲ级肿瘤的瘤周高信号征象、瘤周包膜样低信号征象的出现率差异均无统计学意义(P>0.05)。Ⅰ级肿瘤的瘤周高信号征象、瘤周包膜样低信号征象的出现率均明显不同于Ⅱ、Ⅲ级肿瘤,两者之间差异均具有显著性(P<0.05),Ⅰ级肿瘤瘤周高信号征象、包膜样低信号征象的出现率分别为10.0%、80.0%,而Ⅱ及Ⅲ级肿瘤瘤周高信号征象、包膜样低信号征象的出现率分别为74.4%、15.4%。结论:软组织肉瘤的边缘形态特点与组织病理学分级有关,可在一定程度上反映肿瘤组织的生物学特性。     

Non-invasive MR thermography using the water proton chemical shift

Among various proton magnetic resonance (MR) parameters, such as longitudinal relaxation time, transverse relaxation time, diffusion coefficient and chemical shift, the chemical shift of water protons is recognized as the most reliable indicator of temperature. The chemical shift is the only frequency-based parameter and is independent of the other parameters, which are measured based on the intensity of the MR signal. In this paper, the basic principle and the recent progress in imaging temperature by spectroscopic techniques using the water proton chemical shift are discussed. The advantages of spectroscopic imaging over phase mapping for measuring temperature are that the former can distinguish water resonance from other resonances, and that another resonance can be used as an internal reference to reduce the effects of external magnetic field instability, tissue susceptibility and inter-scan tissue movement or deformation. Methods utilizing various magnetic resonance spectroscopy (MRS) techniques, such as single voxel spectroscopy, conventional magnetic resonance spectroscopic imaging (MRSI), echo planar spectroscopic imaging (EPSI) and line scan echo planar spectroscopic imaging (LSEPSI) are discussed.     

Non-invasive MR thermography using the water proton chemical shift.

Among various proton magnetic resonance (MR) parameters, such as longitudinal relaxation time, transverse relaxation time, diffusion coefficient and chemical shift, the chemical shift of water protons is recognized as the most reliable indicator of temperature. The chemical shift is the only frequency-based parameter and is independent of the other parameters, which are measured based on the intensity of the MR signal. In this paper, the basic principle and the recent progress in imaging temperature by spectroscopic techniques using the water proton chemical shift are discussed. The advantages of spectroscopic imaging over phase mapping for measuring temperature are that the former can distinguish water resonance from other resonances, and that another resonance can be used as an internal reference to reduce the effects of external magnetic field instability, tissue susceptibility and inter-scan tissue movement or deformation. Methods utilizing various magnetic resonance spectroscopy (MRS) techniques, such as single voxel spectroscopy, conventional magnetic resonance spectroscopic imaging (MRSI), echo planar spectroscopic imaging (EPSI) and line scan echo planar spectroscopic imaging (LSEPSI) are discussed.     

肝细胞癌患者1.5T氢质子磁共振波谱分析

背景与目的：磁共振波谱成像是目前唯一能无创性检测活体器官和组织代谢物成分,并进行半定量或定量分析的磁共振成像技术。本研究旨在通过对活体肝脏进行单体素氢质子磁共振波谱（^1H-MRS）扫描,分析健康人肝脏、肝硬化患者再生结节聚集区和肝硬化后肝癌患者肝癌代谢物的变化特点。方法：对20例健康志愿者（对照组）、25例肝硬化（肝硬化组）和23例肝硬化后肝癌（肝癌组）患者行^1H-MRS扫描,观察波谱曲线的特征;测量胆碱复合物（Cho）、脂肪亚甲基（Lip2）峰高及Cho/Lip2比值,并对结果进行记录和比较。结果：波谱检查成功率约为88.2%（60/68）;3个研究组Lip2峰高差异有统计学意义;两两比较,对照组与肝癌组Lip2峰高差异有统计学意义（P＜0.05）,对照组与肝硬化组、肝硬化组与肝癌组Lip2峰高差异均无统计学意义（P＞0.05）;3组人群Cho峰高、Cho/Lip2比值,两两比较,差异均有统计学意义（P＜0.05）。结论：^1H-MRS可无创性反应肝脏的代谢变化,可以为肝细胞癌的诊断及与肝硬化再生结节的鉴别提供相关信息。     

Histopathological outcome of 597 isolated soft tissue tumors suspected of soft tissue sarcoma: a single-center 12-year experience.

BACKGROUND: The aim of this present report was to analyze the patients referred to us with the presumptive diagnosis of soft tissue sarcoma (STS). METHODS: We reviewed all patients referred to us with suspected soft tissue sarcoma (STS) of the extremities or trunk over a 12-year period. RESULTS: We treated 597 patients with soft tissue tumors. Open biopsy revealed soft tissue sarcoma in 318 cases, benign mesenchymal tumor in 124 cases and isolated metastases (ISTM) from carcinomas in 98 patients; other pathologies were found in 57 patients. The primary carcinomas were lung cancer in 26 patients, breast cancer in 19 patients, renal carcinoma in 16 patients, carcinoma of the esophagus in 12 patients, colonic carcinoma in 5 patients, thyroid gland cancer in 6 patients, and in 14 patients carcinoma of unknown primary was diagnosed. CONCLUSIONS: In our collective with soft tissue tumor, 50% of the patients had the diagnosis of soft tissue sarcoma, 20% presented with a metastasis of carcinoma and 20% had a benign tumor. Referring to our results, in patients with the presumptive diagnosis of soft tissue sarcomas, soft tissue metastasis of a primary carcinoma was unexpectedly common, indicating that greater consideration should be given to this differential diagnosis.     

Analysis of telomerase activity and telomere length in bone and soft tissue tumors

Telomerase activation is prevalent in most epithelial tumors, and may be a critical step in cellular immortalization and carcinogenesis. However, telomerase activity in tumors of mesenchymal origin is not well understood. In the present study, we examined telomerase activity in clinical samples from osteosarcoma and soft tissue sarcoma and representative sarcoma cell lines (HOS, OST and Saos2), using the telomeric repeat amplification protocol (TRAP) assay. The cell lines HOS and OST were telomerase-positive, but Saos2 cells lacked telomerase activity and hTERT mRNA expression. Treatment of Saos2 cells with the demethylating agent 5-aza-2'-deoxy-cytidine, alone or together with the histone deacetylase inhibitor tricostatin A, did not induce hTERT mRNA expression. Twenty-six of the 83 sarcoma samples (31.3%) were telomerase-positive [bone sarcoma, 15 of 42 samples (35.7%); soft tissue sarcoma, 11 of 41 samples (26.8%)], whereas neither benign tumors nor normal bone tissue expressed telomerase activity. There was no significant correlation between histological type, tumor staging and telomerase activity. However, patients with telomerase-positive tumors had significantly shorter survival than those with telomerase-negative tumors. There was heterogeneity in telomere length (range, 6-18 kb) among the tumors examined, but there was no significant difference in length between telomerase-positive and -negative tumors. Thus, these mesenchymal tumors comprise heterologous groups, some positive and some negative for telomerase, with long and short telomeres, suggesting multiple carcinogenesis pathways. The present results indicate that telomerase activation is not prevalent in mesenchymal tumors and is not a critical determinant of telomere length, but it may be a prognostic indicator of mesenchymal tumors.     

Rapid detection of metastatic melanoma in lymph nodes using proton magnetic resonance spectroscopy of fine needle aspiration biopsy specimens

Accurate staging of patients with primary cutaneous melanoma includes assessment of regional lymph nodes for the presence of micrometastatic disease. Sentinel lymph node biopsy is highly accurate but is an invasive surgical procedure with a 5-10% complication rate, and requires labour-intensive and expensive histological examination to identify disease. A rapid, accurate and cost-effective non-surgical technique able to detect micrometastatic deposits of melanoma in regional lymph nodes would be of great benefit. Fine needle aspiration biopsies and tissue specimens were obtained from lymph nodes from 18 patients undergoing node resection for metastatic melanoma and five patients undergoing radical retropubic prostatectomy. One-dimensional proton magnetic resonance spectroscopy was undertaken at 360 MHz (8.5 T). Lymph nodes were cut into 3 mm thick slices and embedded. Four sequential 5 microm tissue sections were cut from each block and stained, with haematoxylin and eosin, for S100 protein, for HMB45, and again with haematoxylin and eosin, respectively. Proton magnetic resonance spectroscopy distinguished between benign and malignant lymph node tissue (P < 0.001, separate t-test) and benign and malignant lymph node fine needle aspiration biopsy (P < 0.012) based on the ratio of the integrals of resonances from lipid/other metabolites (1.8-2.5 p.p.m. region) and 'choline' (3.1-3.3 p.p.m. region). In conclusion, one-dimensional proton magnetic resonance spectroscopy on a simple fine needle aspiration biopsy can distinguish lymph nodes containing metastatic melanoma from uninvolved nodes, providing a rapid, accurate and cost-effective non-surgical technique to assess regional lymph nodes in patients with melanoma.     

NMR in cancer. XI. Application of the NMR malignancy index to human gastro-intestinal tumors

One hundred two specimens of human gastro-intestinal tissue taken from eighty-seven individuals were inspected by proton magnetic resonance techniques (at 22.5 Megahertz). The purpose of the study was to evaluate the diagnostic capabilities of the nuclear magnetic resonance (NMR) technique with regard to the diagnosis of malignancy. The combination of two NMR parameters (spin-lattice ((T1) and spin-spin ((T2)) relaxation times) into a malignancy index yielded complete discrimination between the two populations of tissue. The mean and standard deviations obtained were 2.004 +/- 0.342 for normal tissue, and 3.266 +/- 0.642 for malignant specimens. In addition, the NMR technique indicated that histologically normal tissue taken adjacent to the malignancy was pathologically "involved". Analysis of the electrolyte and water content of such tissues confirms this abnormality.     

Nuclear magnetic resonance in cancer, XII: Application of NMR malignancy index to human lung tumours.

Sixty specimens of human lung tissue from 52 individuals were inspected at 22.5 MHz by proton magnetic resonance techniques. The purpose of the study was to evaluate the diagnostic capabilities of the nuclear magnetic resonance (NMR) technique for the diagnosis of malignancy. The combination of two NMR parameters (spin-lattice (T1) and spin-spin (T2) relaxation times) into a malignancy index yielded 3 cases of overlap between the two populations of tissue. The mean and standard deviations obtained were 1.966 +/- 0.262 for normal tissue, and 2.925 +/- 0.864 for malignant specimens. In addition, analysis of the electrolyte and water content of the tissues confirm that factors other than specimen water content influence the relaxation time.     

Matrix metalloproteinase expression in high grade soft tissue sarcomas

Soft tissue sarcomas comprise a heterogeneous group of mesenchymal tumors with varying biological behavior ranging from indolent tumors with no or minimal metastatic risk to aggressive and frequently metastasizing tumors. Among the more common aggressive adult soft tissue sarcomas are malignant fibrous histiocytoma, synovial sarcoma and liposarcoma. Matrix metalloproteinases are enzymes which perform a homeostatic role in mesenchymal tissue and function in both tumorigenesis and metastasis. The objectives of this study are to determine the presence and relative quantity of matrix metalloproteinases (MMPs) -1, -2, -8, -9, and -13; extracellular matrix metalloproteinase inducer (EMMPRIN); and tissue inhibitors of matrix metalloproteinases (TIMP)-1 and -2 in high grade soft tissue sarcoma tumor specimens using real-time PCR. The second objective is to determine if a relationship exists between quantity of EMMPRIN, MMPs, and TIMPs expressed in tumor tissue and disease-free survival. One hundred and forty patients diagnosed with high grade soft tissue sarcomas between 1995-2003 were identified. Tissue blocks and histologic slides were acquired for 41 specimens. Tumor specimens included 29 malignant fibrous histiocytomas, 3 liposarcomas and 11 synovial sarcomas. RNA was extracted and RT-PCR was performed in triplicate. No significant differences were found between the three types of high grade soft tissue sarcomas studied and the expression of MMPs. Interestingly, no relationship was found between high or low levels of MMPs when compared with disease-free survival. Our data support other research which finds variable correlation between MMP expression in soft tissue sarcomas and disease-free survival. We assert that the difference in correlation between MMP expression in carcinomas and sarcomas and disease-free survival is based on the vast phenotypic and genotypic difference between the cells of origin.     

磁共振功能成像在脑肿瘤诊断中的应用

目前,MRI因软组织分辨率高、无辐射及多平面成像等优势已成为脑肿瘤疾病的一种常规检查手段。近年来,随着磁共振技术的发展及磁场强度的增加,一些新的MR功能成像技术已开始越来越多的应用于临床,如磁共振波谱、脑功能成像、灌注成像、磁敏感加权成像、弥散张量成像等,主要用于脑肿瘤之间及脑肿瘤与非肿瘤性疾病的鉴别、肿瘤的分级、指导外科术式的选择、放疗方案的制订等。     

HER-2/neu overexpression detected by immunohistochemistry in soft tissue sarcomas

Sarcomas currently represent 1% of adult malignancies and 15% of pediatric malignancies. To determine the prevalence of HER-2/neu overexpression by the histologic type and to identify a possible predictive role in patients with sarcoma, we performed a retrospective study on subjects with a biopsy-proven diagnosis of a soft tissue sarcoma. HER-2/neu overexpression was evaluated using immunohistochemistry (IHC) performed on paraffin-embedded specimens. An IHC score of 2+ or greater was considered positive for overexpression. Two hundred seventy-three patients with soft tissue sarcoma were identified (164 females, 109 males) with a mean age of 56 (range: 1-93). The most common tumors identified were malignant fibrous histiocytoma (MFH) (18.3%), dermatofibrosarcoma (DFS) (16.1%), leiomyosarcoma (13.2%) and carcinosarcomas (CS) (7.3%). Of the 273 specimens, 29 (10.6%) revealed HER-2/neu overexpression. CS, MFH, and DFS specimens showed the highest incidence of HER-2/neu overexpression (40%, 26%, and 18.2%, respectively). The incidence of HER-2/neu overexpression was found to be significantly higher in patients with a survival of less than 8 months (p = 0.035). This demonstrates that HER-2/neu overexpression is preferentially seen in certain soft tissue sarcomas, and when present is associated with a poorer prognosis in patients with sarcoma. Further studies would delineate whether HER-2/neu overexpression renders sarcomas chemoresistant and thus adversely affects outcome. In addition, there may be a role for Herceptin (trastuzumab) alone, or in combination with conventional therapy, in patients with CS, MHF, and DFS.     

Identification of prognostic markers in bone sarcomas using proton-decoupled phosphorus magnetic resonance spectroscopy

It has been hypothesized that the (31)Phosphorus ((31)P) nuclear magnetic resonance spectrum from certain tumors may provide prognostic information. The goal of the present study was to identify prognostic metabolic markers by using proton-decoupled phosphorus magnetic resonance spectroscopic imaging ((31)P MRSI). Twenty patients with bone [osteogenic (OS) and Ewing's (ES) and/or primitive neuroectodermal tumor (PNET)] sarcoma, treated with chemotherapy and surgery or with chemotherapy alone, underwent (31)P MRSI studies pre- and post-therapy. The studies were performed on a 1.5 Tesla General Electric (GE) clinical scanner equipped with a stand-alone proton decoupler and a dual (1)H/(31)P surface coil pair. The limited sensitivity of the (31)P nucleus required that a large soft tissue component of the disease be located within 10 cm (maximum distance) of the body surface and the use of a highly sensitive coil placed near the skin surface. Proton decoupling and nuclear Overhauser enhancement were used to improve the spectral resolution and signal:noise ratio. Baseline (31)P spectral features and metabolic changes with treatment were compared with treatment outcome. The patients were categorized depending on survival as event-free survivors or those who died. The pretreatment nucleoside triphosphate:inorganic phosphate (NTP:P(i)) ratio, an index of tumor bioenergetic status, was significant (P = 0.003) in differentiating event-free survivors versus those who died. The pretreatment NTP:P(i) was higher in patients who were destined to undergo a durable event-free survival compared with those who died. The results are promising, although a prospective study is necessary for confirmation. (31)P MRSI appears to be a useful tool for the prediction of survival before therapy in bone sarcomas.     

软组织肉瘤的分子靶向治疗研究进展

软组织肉瘤是一类起源于间叶组织的罕见恶性肿瘤，在中国，软组织肉瘤的发病率为1.15/10万人每年，且呈上升趋势。根据世界卫生组织分类，这种恶性肿瘤包含了超过100种不同的组织学亚型，许多分子畸变普遍存在于一些特定的亚型中，但很少有可用于治疗的靶点。软组织肉瘤的一线治疗方案仍然局限于传统的外科手术和化疗，而不是利用分子标志物作为靶点进行治疗。随着对不同组织学亚型发病潜在的分子、基因组机制的了解，促进了软组织肉瘤靶向治疗的发展。将对目前研究较多的软组织肉瘤亚型的靶向治疗进展作一综述。     

Evaluation of total choline from in-vivo volume localized proton MR spectroscopy and its response to neoadjuvant chemotherapy in locally advanced breast cancer

Results of the proton magnetic resonance spectroscopy carried out on normal, benign breast disease and locally advanced breast cancer patients are presented. The in-vivo MR spectra of malignant breast tissue of patients (n = 67) suffering from infiltrating ductal carcinoma are dominated by the water resonance, while the spectra of the unaffected contralateral breast tissue of these patients are mainly dominated by resonance arising from lipids which is similar to the spectra of normal breast tissue obtained from volunteers (controls, n = 16). In addition to the water and lipid peaks, in majority of the patients (approximately 80%) the water suppressed spectra showed a resonance at 3.2 ppm due to choline containing compounds (TCho) before treatment. In patients receiving neoadjuvant chemotherapy, absence/reduction in choline was observed in 89% of the patients. TCho was also observed in 2 of 14 benign lesions. The sensitivity and specificity of in-vivo MRS in detecting TCho in malignant tumours was 78% and 86%, respectively. Observation of TCho before treatment and its disappearance (or reduction) after treatment may be a useful indicator of response of locally advanced breast cancer to neoadjuvant chemotherapy.     

Insulin-like growth factor-I receptor activation blocks doxorubicin cytotoxicity in sarcoma cells

More than 80% of patients with extremity sarcoma ultimately develop metastases to pulmonary sites. Doxorubicin alone or in combination with other chemotherapeutic agents may result in partial or complete tumor response for sarcoma pulmonary metastases. Regardless of the response, there has been no proven survival benefit from cytotoxic chemotherapy in the treatment of localized or metastatic soft tissue sarcoma. Insulin-like growth factor-I receptor (IGF-I-R) activation may contribute to resistance to chemotherapy in mesenchymal neoplasia. IGF-I-R activation by its ligand decreases in vitro cytotoxic response of sarcoma to doxorubicin, the most active agent against soft tissue sarcoma in adults. Furthermore, IGF-I-R is frequently overexpressed in soft tissue sarcoma and may predict poor response to traditional chemotherapy. The effect of doxorubicin on a human soft tissue sarcoma cell derived from a dedifferentiated lung metastasis was evaluated using titrated doxorubicin doses with and without exogenous IGF-I (100 ng/ml). Western blot analysis was performed to evaluate levels of phosphorylated IGF-I-R under control and experimental conditions. In vitro proliferation assays were performed. Nuclear activation through IGF-I receptor mediated pathways prior to exposing sarcoma cells to doxorubicin altered the pattern of response to doxorubicin with enhanced mitogenesis (>2-fold) and blunted doxorubicin cytotoxicity (>10% change in IC50). These data suggest that activation of IGF-I receptor in sarcoma cells is a potential mechanism for tumor resistance to doxorubicin. Inhibition of IGF-I receptor activation represents a novel approach to enhance the degree and duration of response to traditional chemotherapy against soft tissue sarcoma.     

31P magnetic resonance spectroscopic profiles of neoplastic human breast tissues

Phosphorus-containing metabolites of human breast tissues from malignant, benign, and noninvolved breast parenchymal specimens were examined by using techniques of perchloric acid extraction and 31P magnetic resonance spectroscopy. Twenty-four separate resonances arising from the established phosphorylated metabolites of high-energy- and low-energy-phosphate intermediary metabolism were identified and quantitated. Subsequent to magnetic resonance spectroscopic analysis, the data from the three tissue groups were compared and contrasted on a statistical basis by using Scheffé simple and complex contrast procedures. Theories of tumor metabolism and biochemical interactions were invoked, including the tissue high-energy-/low-energy-phosphate modulus, the phosphomonoester/Pi ratio, and 10 other metabolic indices. The data demonstrated the ability of 31P magnetic resonance spectroscopy to differentiate among the three tissue groups. Both benign and malignant tumors demonstrated comparable Warburg effects. Phosphomonoester metabolism was shown to be altered in neoplastic tissues relative to the noninvolved tissues. Phosphocreatine was elevated in benign tumors. This elevation in phosphocreatine plus a parallel elevation in an uncharacterized phosphate resonating at a chemical shift of 3.66 delta permits the important differentiation between malignancy and benignancy in human breast disease. The tissue energy modulus indicated that benign tissue is relatively more aerobic than noninvolved tissue and significantly more aerobic than malignant tissue.     

Clinical applications of proton MR spectroscopy in oncology

Proton magnetic resonance spectroscopy (H1-MRS) has been increasingly receiving more attention from radiologists, neurosurgeons, radiation and medical oncologists in the "in situ" clinical evaluation of human tumors. The utilization of H1-MRS, especially in human brain tumors, coupled to both routine magnetic resonance imaging (MRI) and functional MRI techniques provides greater information concerning tumor grading and extension and characterization of the normal surrounding tissue than what is possible with any other imaging technique alone. In this paper, we will review the current status of proton MR spectroscopy with emphasis on its clinical utility to diagnose tumors, its utility in planning surgical and radiation therapy interventions, and in its use in monitoring tumor treatment.     

Head and neck sarcoma: report of a case treated by intensity-modulated radiation therapy

We report on a 71-year-old woman with parapharyngeal sarcoma. Surgery could not be performed because of the size and location of the tumor. After failure of four cycles of chemotherapy, intensity-modulated radiation therapy (IMRT) achieved complete clinical response and partial magnetic resonance imaging response (80%) at 24 months of follow-up. The results of radiotherapy, especially IMRT, for nonresectable head and neck soft tissue sarcoma are discussed.