子宫肉瘤的处理

主要讨论内容：子宫肉瘤的手术方式；子宫肉瘤化疗；子宫肉瘤放疗；子宫肉瘤激素治疗；子宫肉瘤是女性生殖系统少见的恶性肿瘤，约占妇科恶性肿瘤的1％～3％，其病理类型多样，常见的有子宫平滑肌肉瘤(LMS)、子宫内膜间质肉瘤(ESS)和子宫恶性中胚叶混合瘤(MMMT)。由于子宫肉瘤病因不明，早期诊断困难，所以治疗效果也不理想，5年生存率仅约30％。现结合病例对子宫肉瘤的治疗进行讨论。     

女性盆腔肉瘤的治疗进展

肉瘤是一种较为罕见的恶性肿瘤,易复发和远处转移,预后较差,根据女性盆腔肉瘤发生部位不同,主要有子宫、卵巢、宫颈、阴道、外阴和输卵管肉瘤,以手术治疗为主,原则是肿瘤细胞减灭术,对于子宫肉瘤的标准术式为全子宫切除术,对于子宫平滑肌肉瘤,双附件切除并不是其预后的独立影响因素,而对于子宫内膜间质肉瘤及癌肉瘤,标准术式为全子宫+双附件切除术。其次,针对不同类型不同分期的肉瘤,对盆腔淋巴洁清扫仍存有争议,历年来淋巴结清扫对于肉瘤的预后有无帮助也存在争议。盆腔肉瘤其他的辅助治疗手段包括化疗、放疗、激素治疗以及正处于研究阶段的靶向治疗,辅助治疗的选择可以根据不同类型的肉瘤不同的生物学特性来选择,强调个体化治疗是十分重要的。     

子宫内膜间质肉瘤的研究进展

子宫内膜间质肉瘤是一种来源于间叶组织的子宫肉瘤,其肿瘤细胞形似正常增殖期子宫内膜间质细胞,分为低度恶性子宫内膜间质肉瘤、高度恶性子宫内膜间质肉瘤以及子宫外内膜间质肉瘤.子宫内膜间质肉瘤早期即可能发生浸润和转移,因此早期发现、早期诊断和早期治疗对于本病具有重要的意义.但由于子宫内膜间质肉瘤组织细胞具有多分化潜能,镜下表现...     

子宫肉瘤治疗的进展

子宫肉瘤是一组来源于子宫间质。结缔组织或平滑肌的恶性肿瘤,具有多种不同的组织学形态和生物学活性。主要的病理组织学类型有子宫平滑肌肉瘤、子宫内膜间质肉瘤和子宫恶性中胚叶混合瘤。子宫肉瘤临床少见,约占妇科恶性肿瘤的1％－3％「';但5年生存率仅对％左右［'］。如年代以来,国外相继报道了一些较大样本的临床观察,对该病的临床生物学行为及治疗有了进一步了解。现就其治疗的进展综述如下。一、手术治疗手术治疗是子宫肉瘤最主要的治疗方法。手术的范围为全子宫及双侧附件切除术。由于子宫肉瘤目前根据国际妇产科联盟（FIGO）…     

子宫肉瘤诊治及预后的相关因素

子宫肉瘤是一类临床少见的恶性肿瘤,由于缺乏特异性临床表现,因此术前诊断率极低。子宫肉瘤病理分类较复杂,主要包括平滑肌肉瘤、癌肉瘤、子宫内膜间质肉瘤与未分类肉瘤等。近年来,关于子宫肉瘤病理学特征、临床病理分期、治疗与预后因素等方面的研究均取得了很大进展。     

子宫肉瘤治疗新进展

子宫肉瘤是一种少见的子宫恶性肿瘤,恶性程度高,易局部复发及远处转移,预后不佳。手术为主要的治疗方法,强调术后治疗的规范化及个体化。术后放射治疗并不能改善子宫平滑肌肉瘤患者的无瘤生存率和整体生存率,辅助性化疗因能提高子宫癌肉瘤患者的整体生存率而成为标准治疗方案。曲贝替定用于治疗晚期子宫平滑肌肉瘤有效且安全。靶向药物治疗子宫肉瘤仍处于研究探索阶段。     

子宫肉瘤诊治及预后的相关因素

子宫肉瘤是一类临床少见的恶性肿瘤,由于缺乏特异性临床表现,因此术前诊断率极低。子宫肉瘤病理分类较复杂,主要包括平滑肌肉瘤、癌肉瘤、子宫内膜间质肉瘤与未分类肉瘤等。近年来,关于子宫肉瘤病理学特征、临床病理分期、治疗与预后因素等方面的研究均取得了很大进展。     

子宫肉瘤研究进展

子宫肉瘤是发生于女性生殖器官的恶性肿瘤，其发病率低、预后差，主要有异常阴道出血、腹痛、腹部包块等临床表现。血清乳酸脱氢酶、血清中性粒细胞与淋巴细胞比值（NLR）等血清学指标及超声和磁共振成像等影像学检查可协助子宫肉瘤的术前诊断，但目前其诊断仍主要依靠术后病理结果。子宫肉瘤主要有子宫平滑肌肉瘤、子宫内膜间质肉瘤及子宫腺肉瘤3种病理类型。全子宫及双附件切除是标准手术方式，术后可根据不同病理类型及手术分期选择辅助治疗方式。通过查阅国内外文献，综述子宫肉瘤的临床表现、辅助检查、病理特征、治疗及预后等。     

子宫肉瘤研究进展

子宫肉瘤是发生于女性生殖器官的恶性肿瘤,其发病率低、预后差,主要有异常阴道出血、腹痛、腹部包块等临床表现。血清乳酸脱氢酶、血清中性粒细胞与淋巴细胞比值(NLR)等血清学指标及超声和磁共振成像等影像学检查可协助子宫肉瘤的术前诊断,但目前其诊断仍主要依靠术后病理结果。子宫肉瘤主要有子宫平滑肌肉瘤、子宫内膜间质肉瘤及子宫腺肉瘤3种病理类型。全子宫及双附件切除是标准手术方式,术后可根据不同病理类型及手术分期选择辅助治疗方式。通过查阅国内外文献,综述子宫肉瘤的临床表现、辅助检查、病理特征、治疗及预后等。     

子宫肉瘤的分子基础及靶向治疗的研究进展

子宫肉瘤是一种病因不明的异质性肿瘤，主要由起源于子宫平滑肌、子宫内膜间质（或上皮）和非上皮混合成分的肿瘤组成。不同起源的子宫肉瘤具有不同的生物学特性，对治疗的反应也不尽相同。目前，子宫肉瘤的治疗提倡以手术为主的综合治疗，强调根据患者的肿瘤特点个体化选择合适的治疗方式。近年来，随着分子生物学研究的突飞猛进，越来越多的学者把目光投向了分子靶向治疗的领域，大量的研究发现了子宫肉瘤的基因改变、染色体异常以及细胞周期的失控等分子生物学机制，这些研究使人们逐步认清子宫肉瘤发生、发展的内在规律，并揭示着潜在的关键治疗靶点，尽管目前还没有对子宫肉瘤靶向治疗有效的药物出现，但随着研究的不断深入，靶向治疗子宫肉瘤的可能性正在与日俱增。此外，在一些其他软组织肉瘤的治疗中，靶向治疗所获得的成功也为子宫肉瘤的治疗带来了希望。     

子宫肌瘤恶变及腹腔镜下播散的预防

子宫肌瘤临床常见,但子宫肌瘤发生肉瘤变则少见。子宫一旦发生肉瘤,其恶性程度高,易局部复发及远处转移,预后不佳。在早期常无有效的检查手段来进行筛查和鉴别。若将肉瘤当作肌瘤进行腹腔镜下直接旋切,必然导致肿瘤碎屑及细胞播散,引起盆腹腔的广泛转移。因此,如何早期进行鉴别诊断,术中如何避免旋切带来的播散成为治疗的关键。文章就子宫肌瘤,子宫肉瘤鉴别诊断、腹腔镜下肌瘤旋切手术播散的预防研究进行综述。     

Endocrine aspects of human uterine sarcoma: a preliminary study

The biologic effect of estrogen and progesterone in human uterine sarcoma is poorly understood in comparison to that of endometrial adenocarcinoma. In an attempt to elucidate the endocrine status of these tumors, we have investigated the ability of these tumors to synthesize estrogen by measuring the aromatase activity and studied the effect of aromatase inhibitors on the activity. In addition, the effect of estrogen and progesterone on aromatase activity and the growth pattern of these tumors were studied in cell culture and athymic mice systems. Aromatase activities in eight uterine sarcomas ranged from 0.7 to 37 fmol/hr X mg protein, which were within the range or higher than the activity found in normal proliferative endometrium (0.5 to 3 fmol/hr X mg of protein, means = 1.6, n = 10). These results indicate that uterine sarcomas are capable of producing estrogen. However, the enzyme activity showed no correlation with the morphology of tumors or the age of patients. Results from the kinetic studies of aromatase activity in one of the uterine sarcomas indicated that 19-nortestosterone, testolactone, and aminoglutethimide (the most effective one) inhibited aromatase activity. In addition, induction of aromatase activity in two uterine sarcomas was investigated in cell cultures. Progesterone caused an eightfold increase in activity in a sarcoma that was estrogen and progesterone receptor positive but had no effect in a tumor that was estrogen and progesterone receptor negative. The growth rate of two estrogen/progesterone receptor-negative uterine sarcomas was studied in cell culture and in athymic mice. Progestin, but not estrogen, reduced the growth rate in both systems; 30 nmol/L of estrogen had no effect on the growth rate. In summary, we have found that human uterine sarcoma is able to synthesize estrogen. Progesterone is able to induce the aromatase activity in estrogen/progesterone receptor-positive tumors, and progesterone also suppresses the tumor growth rate in estrogen/progesterone receptor-negative tumors. These results suggest that a select group of uterine sarcomas is sensitive to steroid hormone and that progesterone may be potentially beneficial for therapeutic treatment of select uterine sarcomas.     

Prognostic importance of vascular endothelial growth factor and its receptors in the uterine sarcoma

Vascular endothelial growth factor (VEGF) and its receptors play an important role in tumor progression; however, there is no report regarding this factor in uterine sarcoma. Thirty-nine patients with uterine sarcoma, 14 carcinosarcomas, 4 endometrial stromal sarcomas, and 21 leiomyosarcomas, were studied. By immunohistochemical staining, VEGF was not detected in normal uterine smooth muscle, but VEGF receptor-1 (flt-1) and VEGF receptor-2 (flk-1) were observed in 14 and 4 of 14 normal smooth muscles, respectively. Of 39 sarcomas, 25 expressed VEGF, and 38 and 34 sarcomas expressed flt-1 and flk-1 at various intensities, respectively. The staining intensity of VEGF, flt-1, and flk-1 was significantly higher in sarcoma than in normal uterine smooth muscle, but that of phospho-flt-1 (p-flt-1) was significantly lower in sarcoma than in normal uterine smooth muscle. When sarcomas were divided into two groups according to staining intensity, a significant difference in survival curves was observed in only p-flt-1 of leiomyosarcoma (P= 0.008), and in all sarcomas, a lower survival curve was also observed in the high staining intensity group than in the low staining intensity group, although there was no significant difference (P= 0.102). In conclusion, VEGF and its receptors are suggested to be involved in progression of uterine sarcoma, but only the p-flt-1 level significantly affected the survival of leiomyosarcoma patients.     

术前如何鉴别诊断子宫肉瘤与子宫肌瘤

子宫肉瘤是一种少见的子宫恶性肿瘤,恶性程度高,术后复发率高,预后差。由于子宫肉瘤缺乏典型的临床表现、可靠的影像学特征和特异性的肿瘤标志物,准确的术前诊断非常困难。综合考虑多种因素,包括高危因素和临床症状、盆腔超声和MRI以及组织活检病理等,有助于术前鉴别子宫肉瘤与子宫肌瘤。     

Endolymphatic Stromal Myosis Associated with Tamoxifen Use

A case of low-grade endometrial stromal sarcoma (endolymphatic stromal myosis) occurring in a patient who had received tamoxifen citrate for 3 years following surgical treatment for breast cancer is presented. Endometrial adenocarcinomas have been the most frequently reported tumor associated with tamoxifen use. More recently, uterine sarcomas have also been described in association with the use of tamoxifen. This report adds only the second case of a low-grade endometrial stromal sarcoma associated with tamoxifen use. As in the first report, the tumor demonstrated a sex-cord-like pattern of differentiation, an uncommon feature of endometrial stromal sarcomas. This suggests a possible association between tamoxifen use and the subsequent development of low-grade endometrial stromal sarcoma.     

Clinical outcome and prognostic factors in 100 cases of uterine sarcoma: experience in Helsinki University Central Hospital 1990-2001

ObjectiveUterine sarcomas are rare malignant gynecological tumors with poor prognosis. In this study clinical data on all uterine sarcoma patients treated at Helsinki University Central Hospital (HUCH) between 1990–2001 were retrospectively evaluated.MethodsMedical records were reviewed and data collected on all uterine sarcomas treated during a 12-year period at HUCH. Kaplan–Meier survival curves were generated and those variables found to be statistically significant in univariate analysis were examined by multivariate analysis using Cox's proportional hazards regression model.ResultsOne hundred patients met the study requirements: 40 cases were diagnosed as carcinosarcomas, 39 as leiomyosarcomas and 21 as endometrial stromal sarcomas. First-line treatment was surgery in 98% of the patients. Seventy-eight of the patients were treated by means of adjuvant therapy. A complete response was achieved in 80% and a partial response in 4% of the cases. The 2-, 5- and 10-year overall survival rates were 62%, 51% and 38% and disease-specific survival rates were 64%, 56% and 44% (all sarcomas). In multivariate analysis, stage, age, tumor size and parity were proven to have independent influences on overall survival, and stage, tumor size and parity also independently influenced disease-specific survival.ConclusionsIn this study, survival rates were better than in nearly all previous retrospective studies of uterine sarcomas. It seems that higher parity could have a negative influence on survival in cases of uterine sarcoma.     

Microsatellite instability in uterine sarcomas

Abstract. Amant F, Dorfling CM, Dreyer L, Vergote I, Lindeque BG, Van Rensburg EJ. Microsatellite instability in uterine sarcomas.
Studies have shown a 15–30% frequency of microsatellite instability in endometrial cancer. In addition, we found a 21% frequency of microsatellite instability in endometrial cancer. Our aim was to investigate the presence of microsatellite instability and loss of heterozygosity in uterine sarcomas. The records of 69 women referred to Kalafong Academic and Pretoria Academic Hospital with a primary diagnosis of uterine sarcoma were reviewed. At histological review of 43 cases with a primary diagnosis of leiomyosarcoma, diagnosis of mitotically active leiomyoma was made in 21. Diagnosis of carcinosarcoma was made in 21 cases and endometrial stromal sarcoma in five. In all cases, genomic DNA was extracted from normal myometrium and tumor and analyzed for microsatellite instability and loss of heterozygosity. High-frequency microsatellite instability was absent in leiomyosarcoma, endometrial stromal sarcoma, and mitotically active leiomyomas and was observed in 1 (5%) carcinosarcoma. Loss of heterozygosity for chromosome 11 was present in 8/48 (17%) of uterine sarcomas, equally distributed between leiomyosarcomas (4/22 = 18%) and carcinosarcomas (4/21 = 19%). There was no loss of alleles in endometrial stromal sarcoma nor mitotically active leiomyomas. In conclusion, it is suggested that tumor suppressor genes may play a role in the tumorigenesis of uterine mesenchymal cells, whereas mismatch repair genes contribute to the carcinogenesis of endometrial cancer.     

Mutational analysis of the PTEN gene in human uterine sarcomas

OBJECTIVE: Uterine sarcomas are rare, lethal cancers, and little is known about their molecular etiology. The PTEN gene is located on chromosome 10q23.3, a region that displays frequent loss of heterozygosity in human uterine sarcomas. PTEN mutations have been described in 40% to 60% of uterine adenocarcinomas. To determine whether the PTEN gene is involved in the pathogenesis of uterine sarcoma, we analyzed deoxyribonucleic acid from uterine sarcomas and cell lines. STUDY DESIGN: Single-strand conformation analysis and direct sequencing of deoxyribonucleic acid were used to screen for PTEN mutations. RESULTS: Silent polymorphisms were detected in 2 of 36 primary uterine sarcomas. A 4-base pair deletion and a point mutation producing a stop codon were identified in 1 cell line. CONCLUSIONS: Mutational inactivation of PTEN does not play a major role in uterine sarcoma tumorigenesis, and another gene or genes on chromosome 10q may be implicated as a cause of these cancers. Differences in the molecular alterations underlying the development of uterine sarcomas and adenocarcinomas are significant.