上皮性卵巢癌细胞凋亡指数和肿瘤微血管密度与肿瘤复发的关系

目的　研究上皮性卵巢癌细胞凋亡、增殖状态和肿瘤微血管生成及其与肿瘤复发之间的关系。方法　对 1996年 10月至 1999年 10月间 45例上皮性卵巢癌石蜡组织切片采用DNA原位缺口末端标记 (TUNEL)方法,检测细胞凋亡指数(AI);应用FⅧ相关抗原及增殖细胞核抗原 (PCNA),采用SABC法,检测卵巢癌中的肿瘤微血管密度(MVD)及细胞增殖状态(PI)。结果　不同的组织类别,临床分期,组织分级中AI、PI差异无显著性(P>0.05)。卵巢癌中的AI/PI平均值为 0.0621±0.0281,临床Ⅲ ~Ⅳ期肿瘤AI/PI显著低于临床Ⅰ ~Ⅱ期肿瘤(P<0.05);MVD在不同组织类别,不同临床分期中的差异有显著性意义(P<0.05); 6例复发性上皮性卵巢癌中AI/PI与MVD均高于未复发者。结论　上皮性卵巢癌组织中凋亡的发生远低于细胞的增殖,细胞凋亡的相对减少与细胞增殖共同参与了肿瘤的发展。随着卵巢癌的进展,肿瘤血管生成是增多的。复发性上皮性卵巢癌中AI/PI与MVD均高于未复发者。     

小儿造血干细胞移植后出血性膀胱炎的临床特征与危险因素分析

目的 分析小儿造血干细胞移植(HSCT)后出血性膀胱炎(HC)的临床特点，探讨其发病危险因素。 方法 对1998年10月至2004年6月中山大学附属二院儿科完成的52例小儿HSCT后11例HC的临床资料进行回顾分析。 结果 11例HC中轻度(Ⅰ~Ⅱ度)6例，重度(Ⅲ~Ⅳ度)5例；早发性4例，迟发性7例；发病时间为术后+2d至+25d(中位数为+15d)，病程3~60d(中位数为17d)。临床表现均有血尿，其中典型尿频、尿急、尿痛及肉眼血尿7例。HC患儿组中性粒细胞植入时间和血小板植入时间与非HC患儿组比较差异无显著性(P>0.05)。受者移植年龄≥6岁、aGVHD阳性、CMV感染组的HC发生率分别高于年龄<6岁(321%和83%，P<0.05)、GVHD阴性(34.6%和7.7%，P<0.05)、CMV未感染组(62.5%和13.6%，P<0.05)。 结论 小儿HSCT后HC有其自身的临床特征；受者移植年龄≥6岁、aGVHD阳性、CMV感染为其发生的危险因素。     

血清CA125半衰期判定卵巢上皮性癌预后的价值

目的 探讨血清ＣＡ１２５半衰期在卵巢上皮性癌中的预后价值。方法 回顾性分析３０例卵巢上皮性癌患者在化疗过程中血清ＣＡ１２５半衰期值（ｔ１／２）与生存时间的关系。结果 血清ＣＡ１２５半衰期值（ｔ１／２）≤２０天组的中位生存时间为３６个月,ｔ１／２〉２０天组中完全缓解率为２７．３％,两者存在极显著差异（ｐ＝０．００１）。多因素生存分析表明：ＣＡ１２５半衰期和细胞分级、残余瘤灶大小均是独立的预后因素。结     

The role of thrombocytosis in prognostic evaluation of epithelial ovarian tumors

Background  Thrombocytosis has been reported in a variety of solid tumors, including certain gynecologic cancers such as endometrial, vulvar, and cervical cancers. The present study aims to determine the incidence of thrombocytosis in women with epithelial ovarian tumors and to evaluate its association with clinical and pathologic prognostic factors. Material and methods  Between January 2001 and December 2006, 292 patients were diagnosed with epithelial ovarian tumors, and they underwent primary surgical treatment and subsequent platinum-based chemotherapy at the Gynecologic Oncology Department of the study center. The medical records of these patients were evaluated retrospectively. Results  Of the 292 women with epithelial ovarian tumors undergoing primary surgical exploration, 124 (42.5%) had thrombocytosis, indicating platelet counts >400 × 10⁹/l. Patients with thrombocytosis were found to have statistically higher levels of preoperative CA-125 levels, more advanced stage disease, higher grade tumors, and shorter periods of survival. Thrombocytosis is a significant negative prognostic factor for survival in patients with epithelial ovarian tumors. Conclusions  Thrombocytosis is frequently detected in preoperative evaluation of women diagnosed with epithelial ovarian tumors. The data obtained by the previous and present studies suggest that thrombocytosis is associated with factors reflecting a more aggressive tumor biology, and predicting poor survival in women with epithelial ovarian tumors. However, these data are limited by the retrospective nature of the studies and do not confirm a casual relationship between thrombocytosis and tumor behavior. Molecular studies investigating the expression of platelet secretory factors are required to clarify the differences among data provided by the literature.     

Prognostic factor analysis, for patients with no evidence of disease after initial chemotherapy for advanced epithelial ovarian carcinoma

Although the results from chemotherapy for advanced ovarian carcinoma have improved over the past 15 years with the introduction of platinum compounds, there are still a large number of patients who will relapse from complete response (clinical or pathological) to first line therapy, and there is little published data on prognostic factors for survival after relapse. A total of 270 patients from two randomized trials in ovarian carcinoma conducted in Scotland were reviewed and the data from 117 patients who were disease free after first line treatment were analyzed to determine prognostic factors associated with disease-free survival and survival after relapse respectively.
The most important prognostic factors adversely influencing time to relapse were the presence of ascites at presentation and an advanced tumor stage. For time from relapse to death, the most important adverse features were: early relapse, no chemotherapy at relapse, histology other than serous and stage at diagnosis (either stage IC/II or stage III/IV with residual disease 2 cm). From our results, 26% of patients who achieve complete response are alive and disease-free after 5 years, while 56% relapsed within 2 years. Of the patients whose disease-free period following initial complete response extends beyond 600 days, 50% can expect a further period of at least 600 days following relapse and subsequent therapy. Patients with ascites and advanced stage may be suitable for consideration of a more aggressive approach (high dose chemotherapy) once complete response is confirmed, the aim being to improve the disease-free period.     

The search for biomarkers to direct antiangiogenic treatment in epithelial ovarian cancer

Antiangiogenic agents have demonstrated improved progression-free survival in women with primary and recurrent epithelial ovarian cancer (EOC). Biomarkers that predict outcomes in patients treated with antiangiogenic agents are being investigated to rationally direct therapy for women most likely to benefit from these agents. Among the most promising plasma-based biomarkers are vascular endothelial growth factor (VEGF)-A, fibroblast growth factor, platelet-derived growth factor, angiopoietin-2, and VEGF receptor-2. While these biomarkers have been correlated with prognosis, they have not been shown to predict benefit, specifically from anti-VEGF therapy, highlighting the need for alternative biomarkers, including molecular and clinical factors, which may be predictive of outcome in women with ovarian cancer treated with antiangiogenic agents. Biomarkers are currently being investigated as secondary outcomes in several ongoing phase II and phase III clinical trials of antiangiogenic agents in patients with EOC. Molecular techniques, such as microarray analyses, and imaging techniques, such as dynamic contrast-enhanced magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography, are also being explored in this field. In this review, we provide a comprehensive overview of current biomarker research, with an emphasis on angiogenic biomarkers associated with EOC.     

复发性上皮性卵巢癌二线化疗的回顾性分析

目的 探讨复发性上皮性卵巢癌二线化疗的疗效及可行性。方法 回顾性分析51例复发性卵巢上皮性恶性肿瘤，其中32例用顺铂 异环磷酰胺 足叶乙甙方案及顺铂 拓扑替康化疗。结果 二线化疗有效率62．5％；二线化疗后平均生存期13．54个月，明显高于未治疗组。但总生存期无差别。两种化疗方案(PIE化疗组和拓扑替康组)相比对生存期影响无明显差别。结论 顺铂、异环磷酰胺加足叶乙甙及顺铂 拓扑替康联合化疗治疗复发及难治性上皮性卵巢癌有一定疗效，可供临床选用。     

Management of recurrent epithelial ovarian carcinoma

Despite the standardisation of surgical techniques and significant progress in chemotherapeutics over the last 30 years, advanced epithelial ovarian cancer remains the most lethal gynaecological malignancy in the western world. Although the majority of women achieve a remission following primary therapy, most patients with advanced stage disease will eventually relapse and become candidates for 'salvage' therapy. The chances of a further remission depend on factors such as the 'treatment-free interval', and there are now a large number of chemotherapy agents with activity in ovarian cancer available to the oncologist. Recent randomised studies have reported on survival benefits for chemotherapy in recurrent disease, and therefore careful and appropriate selection of treatments has assumed a greater importance. This article reviews the most current data, and discusses the factors involved in making individualised treatment decisions.     

Comparison between primary peritoneal and epithelial ovarian carcinoma: a population-based study

OBJECTIVE: This study was undertaken to characterize primary peritoneal carcinoma (PPC) compared with ovarian carcinoma (OvC). STUDY DESIGN: Within the framework of a nationwide epidemiologic Israeli study, 95 PPC patients were identified and compared with 117 FIGO stage III-IV epithelial OvC patients matched by age and continent of birth. Data were abstracted from medical records and personal interviews. RESULTS: Our data confirm the similarities between PPC and OvC. A higher rate of abdominal distention, volume of ascites, and malignant cells in ascitic fluid and lower rate of pelvic palpable mass and personal breast cancer history were found in the PPC compared with the OvC group. The overall survival was similar in both groups (30-33 months). In optimally cytoreduced patients, survival was better in the OvC group. Diameter of residual disease was associated with better survival only in the OvC group. CONCLUSION: The clinical differences do not enable a preoperative distinction between the neoplasms.     

晚期卵巢上皮癌以急腹症为首发症状12例分析

目的：探讨以急腹症为首发症状的晚期卵巢上皮癌的临床特点与预后。方法：回顾分析1986年1月至1997年12月我院收治的以急腹症作为首发症状的晚期上皮性卵巢癌12例。结果：中位年龄43岁（34-61岁）。Ⅲa期1例,Ⅲc期10例,Ⅳ期1例。分化1级1例,2级6例,3级5例。术中发现肿瘤破裂8例（其中合并肿瘤扭转2例,肿瘤出血1例）,单纯急腹痛2例,肿瘤性肠梗阻、肠穿孔各1例。5例行全子宫、双附件、大网膜切除,7例行姑息性肿瘤切除。仅2例手术后残留灶直径≤1cm。11例术后接受铂类为基础的联合化疗2-6疗程。生存期＜12月9例,12-23月2例（包括治疗14月后失访1例）,仅1例存活25月。5例（41.7%）有肿瘤家庭史。结论：晚期上皮性卵巢癌以急腹症为首发症状者有明显的肿瘤家族史,预后差。     

Interleukin-7 and suppression of local peritoneal immunity in ovarian carcinoma.

OBJECTIVES: To investigate the epithelial ovarian carcinoma (EOC) secretion of interleukin-7 (IL-7). METHODS: Levels of IL-7 were assayed by enzyme-linked immunoadsorbent assay and IL-7 mRNA, and protein expression in tissues and cell lines were detected by RT-PCR and immunohistochemistry. RESULTS: The median serum IL-7 level in patients with EOC (32 cases; 32.49 pg/ml) was significantly higher than that of patients with benign tumors (16 cases; 7.59 pg/ml) and healthy women (16 cases; 10.64 pg/ml) (P<0.05). The median peritoneal fluid IL-7 level in patients with EOC (17.39 pg/ml) was slightly higher than that of patients with benign tumors (14.09 pg/ml), but not significantly so (P>0.05). There were positive correlations between the serum and peritoneal fluid IL-7 levels in both ovarian cancer and benign group (P<0.05, both). Only two EOC specimens expressed IL-7 mRNA, and no IL-7 protein positive was found in any specimens. CONCLUSIONS: Epithelial ovarian carcinoma cells rarely express IL-7, and IL-7 levels are decreased in the ascitic fluid of patients with EOC.     

Splenectomy during primary and secondary cytoreductive surgery for epithelial ovarian carcinoma

Scarabelli C, Gallo A, Campagnutta E, Carbone A. Splenectomy during primary and secondary cytoreductive surgery for epithelial ovarian carcinoma. Int J Gynecol Cancer 1998; 8 : 215–221.
Splenectomy is occasionally indicated to achieve optimal cytoreduction during surgery for epithelial ovarian cancer. Between January 1989 and December 1996, 40 epithelial ovarian cancer patients underwent splenectomy: 14 patients during primary surgery and 26 during secondary cytoreductive surgery. Splenectomy was performed for tumor reduction in 34 patients (85 %) and for iatrogenic injury in six patients (15%). The spleen was removed because of parenchymal splenic metastases in nine patients (22.5 %), significant hilar and/or capsular disease in 10 patients (25 %), and perisplenic disease in 15 patients (37.5%). The histopathological diagnosis of the resected spleens showed microscopic hilar disease in four patients who had the spleen removed because of iatrogenic injury and no disease in only two patients. Splenectomy could be carried out with an acceptable morbidity. Left-sided pleural effusion was the most frequent complication. The estimated two-year survival rate for patients who underwent splenectomy during primary surgery with no residual disease and <2 cm intraperitoneal residual disease was 83% and 42%, respectively. Nine of these patients (64.3%) had recurrent disease. The median time to recurrence was 11 months (range 5–18). The estimated two-year survival rate for patients who underwent splenectomy during secondary surgery with no residual disease and <2 cm intraperitoneal residual disease was 78% and 24%, respectively. The estimated three-year survival rate was 0% for all these patients. The results of the present study show that splenectomy, if necessary to achieve optimal debulking, should be considered in previously untreated patients with no intraperitoneal residual disease and in patients with late (>1 year) recurrent disease.     

Expression of GLUT-1 in epithelial ovarian carcinoma: correlation with tumor cell proliferation, angiogenesis, survival and ability to predict optimal cytoreduction

Objective

GLUT-1 is involved at various steps in the processes of tumor progression. The objective of this study was to examine the relationship between GLUT-1 expression and tumor proliferation and angiogenesis in epithelial ovarian carcinoma.

Materials and methods

Specimens from 213 patients with epithelial ovarian carcinoma were evaluated by immunohistochemistry for GLUT-1, Ki-67, and vascular endothelial growth factor. Tumor microvessel density was assessed with CD34 immunostaining. We investigated the relationships between GLUT-1 expression and clinicopathologic characteristics, tumor angiogenesis (tumor MVD and vascular endothelial growth factor expression), and tumor proliferation (Ki-67). The effect of GLUT-1 expression on patient survival and on the volume of residual disease after cytoreduction was determined.

Results

There was a significant positive correlation between expression of GLUT-1, Ki-67, and microvessel density. In univariate survival analysis, high GLUT-1 expression, high Ki-67 expression and high tumor microvessel density showed a significant impact on patient survival (p = 0.0001). In multivariate analysis including patients with all tumor stages, after controlling for age, race, stage, grade, MVD, and the 3 markers (GLUT-1, Ki-67 and VEGF), only age (HR 1.5; 95% CI 1-2.3), stage (HR 3.6; 95% CI 1.8-7.5) and grade (HR 2.3; 95% CI 1.2-4.5) retained their significance as independent poor prognostic factors. Tumors simultaneously overexpressing GLUT-1 and Ki-67 were less likely to be optimally cytoreduced as compared to tumors overexpressing only one or neither of those two markers (OR: 3.8, p = 0.01).

Conclusion

Expression of GLUT-1 correlates with tumor proliferation and microvessel density in epithelial ovarian carcinoma. In addition, patients with rapidly proliferating advanced stage tumors overexpressing GLUT-1 have a lesser chance for optimal cytoreduction.     

Response of combination platinum and gemcitabine chemotherapy for recurrent epithelial ovarian carcinoma

OBJECTIVE: It has been postulated that gemcitabine inhibits DNA repair, and platinum resistance is due to increased DNA repair activity. The addition of gemcitabine to platinum-based agents may have synergistic tumoricidal activity. METHODS: Retrospective chart review of all patients with recurrent, persistent, or progressive fallopian tube or ovarian carcinoma treated with a platinum-based compound and gemcitabine from 2001 to present was performed. RESULTS: Twenty-nine patients on second to eight line chemotherapy met inclusion criteria. The median age was 53 years. Twenty-two patients received cisplatin and gemcitabine, and 7 patients received carboplatin and gemcitabine based on results of chemoresistance assays or prior chemorelated toxicities. The intent to treat was with six cycles of gemcitabine (1000 mg/m(2)) and either cisplatin (75 mg/m(2)) or carboplatin (AUC 5) day 1 and gemcitabine only on day 8 of a 21-day cycle. The median number of cycles administered was six. There were 20 grade 3 and 4 toxicities and 63% of patients by cycle 6 needed erythropoietin marrow support and 19% needed GCSF support by cycle 4. Twenty-one patients required discontinuation of day 8 that most commonly occurred at cycle 4. Eleven (38%) had CR, 5 (17%) had PR, 6 (21%) had SD, and 7 (24%) had PD, which is a 55% overall response. Nineteen of 29 patients (66%) showed platinum resistance to initial therapy. Of those, four (21%) had CR, four (21%) had PR, six (32%) had SD, and five (26%) with PD, which demonstrates a 42% overall response rate for this particular subset of patients. CONCLUSIONS: Adjuvant combination platinum-based agent with gemcitabine is a very effective and well-tolerated treatment for recurrent fallopian tube or ovarian carcinoma; even in those who exhibit initial platinum resistance.     

The results of treatment of epithelial ovarian cancer after centralisation of primary surgery. Results from North Jutland, Denmark

OBJECTIVE: The study was performed to evaluate the results of treatment of ovarian carcinoma after the introduction of centralised primary surgery in the County of North Jutland, Denmark. METHOD: Prospective study of consecutive cases of ovarian cancer undergoing primary surgical treatment at the Gynecologic Oncologic Center after the introduction of centralised primary surgery. Results of treatment recorded up to the date of last examination or death. RESULTS: From 1999 to 2002, 107 patients with primary epithelial ovarian cancer underwent primary surgery at the Gynecologic Oncologic Center, Aalborg. This corresponds to 95.5% of patients with invasive carcinoma in the County of North Jutland. All patients with Stage I to Stage IIIB disease had a complete, macroscopically radical cytoreduction performed. In patients with Stage III and IV invasive tumors, the optimal debulking rate was 79.5%, and, in Stage IIIC and IV, the optimal debulking rate was 78.2%. Intra-operative and post-operative complications were generally few. Post-operative death, defined as death within 30 days after surgery, was observed in 4 cases (3.7%). After primary surgery, platinum-based chemotherapy was given in most cases. For Stage I to IV invasive cancer, the median survival was 46 months. In patients with Stage IIIC and IV disease, the median survival was 32 months. In optimally debulked Stage IIIC and IV disease, the median survival was 41 months. CONCLUSIONS: The results indicate a survival benefit after introduction of centralised primary surgery. Compared to existing national and regional data on survival in ovarian cancer, the results indicate an increase in median survival for all stages of approximately 15 months. Centralisation of primary surgery to centres with the necessary expertise may be the most significant way to increase survival in ovarian cancer in Denmark.     

Cytoreductive surgery in the primary management of advanced epithelial ovarian carcinoma: a topic for debate

While there is no doubt that surgical resection of early stage ovarian cancer can be curative, the effect of cytoreductive surgery on the prognosis in advanced disease is less certain. A recent EORTC study does suggest that intervention debulking surgery might improve survival and this requires urgent confirmation. Extensive cytoreductive surgery, removing bowel, parts of the urinary tract or lymph nodes, may have little impact on the survival of women with advanced disease and can result in substantial morbidity. Discretion and experience are required in determining the appropriate radicality of tumor resection to avoid predictable impairment of quality of life.