Serum α1-acid glycoprotein in epithelial ovarian cancer

Fifty-six patients with ovarian adenocarcinoma receiving chemotherapy were monitored with serum α₁-acid glycoprotein (AGP) levels. The mean and standard deviation of serum AGP levels for 63 healthy controls were 0.88 ± 0.469 mg/ml. A serum level above 1.80 mg/ml was considered as above normal level. Five patients had evidence of persistent ovarian carcinoma and had elevated AGP levels. Sixteen patients had normal serum AGP levels and had no evidence of persistent ovarian cancer at second-look laparotomy. However, 35 patients had false-negative AGP levels at the time they had persistent tumor. Although the specificity of the AGP level was 100%, the sensitivity was only 12.5% and the overall accuracy 37%. Therefore, it would appear that serum AGP levels are not of value in monitoring patients with ovarian adenocarcinoma.     

IGFBP-4 tumor and serum levels are increased across all stages of epithelial ovarian cancer

Anti-VEGF treatment has proven effective in recurrent ovarian cancer. However, the identification of the patients most likely to respond is still pending. It is well known that the angiogenesis is regulated by several other pro-angiogenic proteins, e.g. the platelet - derived growth factor (PDGF) system and the fibroblast growth factor (FGF) system. These other signaling pathways may remain active or become upregulated during anti-VEGF treatment. The aim of the present study was to investigate if potential changes of PDGF-BB, PDGF-AA, and FGF2 before and during bevacizumab treatment had predictive value for early progression or survival. Furthermore, we wanted to investigate the importance of serum VEGF in the same cohort. This study included 106 patients with chemotherapy-resistant epithelial ovarian cancer who were treated with single agent bevacizumab as part of a biomarker protocol. Patients were evaluated for response by the Response Evaluation Criteria In Solid Tumors (RECIST) and/ or Gynecologic Cancer Intergroup (GCIG) CA125 criteria. Serum samples were collected at baseline and prior to each treatment. FGF2, PDGF-BB, PDGF-AA were quantified simultaneously using the Luminex system, and VEGF-A was measured by ELISA. Eighty-eight baseline samples were avaliable for FGF2, PDGF-BB, PDGF-AA analysis, and 93 baseline samples for VEGF. High baseline serum VEGF was related to poor overall survival. Furthermore, high serum PDGF-BB and FGF2 was of prognostic significance. None of the markers showed predictive value, neither at baseline level nor during the treatment.     

Heterogeneity of antigen expression in advanced epithelial ovarian cancer

Immunohistochemical techniques were used to evaluate the expression of six antigens (CA 125, TAG 72, CA 19-9, OVTL3, DF3, and transferrin receptor) in frozen sections from the primary tumor and metastases of 20 patients with epithelial ovarian cancer. Heterogeneous expression of most antigens was observed within a given tumor nodule, but in each patient the proportion of cells expressing an antigen was similar in the primary tumor and metastases. To explore the stability of the antigenic phenotype of individual cells, we studied CA 125 expression in an ovarian cancer cell line. Cells were separated into CA 125-positive and -negative groups using fluorescence-activated cell sorting. After the two groups of cells were recultured separately, only 38% of cells originally sorted as CA 125 positive still expressed CA 125, whereas 27% of cells sorted as CA 125 negative expressed CA 125. That cells may gain or lose CA 125 expression in culture suggests that expression of CA 125 by ovarian cancer cells is not a stable trait.     

Activity of bevacizumab (rhuMAB VEGF) in advanced refractory epithelial ovarian cancer

BACKGROUND: Angiogenesis is pivotal in the development and progression of ovarian cancer and is an ideal candidate for novel treatment approaches. CASE: A case of advanced, recurrent and refractory serous carcinoma is presented that responded to bevacizumab 15 mg/m2 intravenously every 3 weeks after failing eleventh line cytotoxic chemotherapy and radiation. An objective durable response lasting at least 5 months was documented. CONCLUSION: Bevacizumab has activity in epithelial ovarian carcinoma and larger scale trials are indicated.     

Role of laparoscopy to evaluate candidates for complete cytoreduction in advanced stages of epithelial ovarian cancer

Abstract.   Deffieux X, Castaigne D, Pomel C. Role of laparoscopy to evaluate candidates for complete cytoreduction in advanced stages of epithelial ovarian cancer. Int J Gynecol Cancer 2006; 16(Suppl. 1): 35–40.
The objective of this study was to evaluate the role of laparoscopy in selecting candidates for complete cytoreduction surgery in epithelial ovarian carcinoma. We performed an explorative laparoscopy in 15 women presenting with advanced ovarian carcinoma, and for whom the preoperative evaluation was considered unsatisfactory, to define the possibility of achieving a complete cytoreduction. We focused on three sites of carcinomatosis: bowel, liver pedicle, and right diaphragmatic dome. Laparoscopic evaluation was successful in all 15 patients. Four patients were considered to have unresectable carcinomatosis because of extensive involvement of the small bowel and therefore had no laparotomy. These women underwent neoadjuvant chemotherapy in the following 2 weeks. Eleven patients were considered to have resectable peritoneal carcinomatosis (PC). Ten women had no macroscopic residual tumor after surgery. A modified posterior exenteration was performed in five patients. The laparoscopic exploration had underestimated the liver pedicle involvement in two patients, but only one had an infracentimetric residual tumor after surgery. Laparoscopy is a reliable method of exploring PC in advanced-stage ovarian cancer. Laparoscopy may obviate the need for unnecessary laparotomy in many cases and may, therefore, contribute to a better quality of life for patients found to have unresectable disease.     

Tamoxifen in patients with advanced epithelial ovarian cancer

Tamoxifen was administered to 30 patients with persistent or recurrent epithelial ovarian cancer following initial plantinum-based chemotherapy. Two complete remissions (lasting 41 months and 12 months, respectively) were documented (6.6%), while 10 patients (33.3%) had stabilization of disease for a mean duration of 11.5 months. Tamoxifen was not associated with any significant toxicity and is a reasonable therapeutic option for patients with persistent or recurrent ovarian cancer, although it is only associated with modest activity. This paper reviews our experience with tamoxifen and summarizes the world literature.     

Interval debulking surgery in advanced epithelial ovarian cancer

Cytoreductive surgery and chemotherapy are the mainstay for the treatment of advanced epithelial ovarian cancer. In order to minimize the tumour burden before chemotherapy, cytoreductive surgery is usually performed first. The importance of the amount of residual disease as the main prognostic factor for patients suffering from advanced disease has been almost universally accepted even in the absence of prospective randomized trials addressing the benefit of cytoreductive surgery. In the last decade, the value of debulking surgery after induction chemotherapy - interval debulking surgery, IDS - has been widely debated, especially after the completion of a prospective randomized study from the EORTC addressing the introduction of a surgical procedure with debulking intent preceded and followed by cytoreductive chemotherapy. The rationale of such a strategy in the context of the primary treatment of advanced ovarian cancer lies in a higher cytoreductibility to the 'optimal' status forwarded, and possibly facilitated, by chemotherapy. The results demonstrated a prolongation of both progression-free survival and median survival in favour of patients randomized to IDS (5 and 6 months, respectively). Multivariate analysis revealed IDS to be an independent prognostic factor which reduced the risk of death by 33% at 3 years and by 48% in subsequent re-evaluation after more than 6 years of observation. Despite the above, results have been questioned by many, leading the GOG to perform a similar study which has been concluded very recently. Nevertheless, the main concern regarding the application of IDS in all instances relates to the morbidity of two major surgical procedures integrated within a short period during which cytotoxic chemotherapy is also administered. Neoadjuvant chemotherapy has been recently proposed to avoid a non-useful surgical procedure in patients considered 'optimally unresectable' after diagnosis of advanced ovarian cancer. Whether or not this newer approach will translate into a longer survival with a better quality of life is going to be addressed by a novel EORTC study. Finally, the concept of a 'chemical' cytoreduction preceding and facilitating a subsequent 'surgical' effort has been recently introduced also in the treatment of recurrent disease. The EORTC has recently initiated a prospective randomized study (LOROCSON - Late Onset Recurrent Ovarian Cancer: Surgery or Not) to validate the importance of such an approach to be balanced with medical treatment alone not only in terms of survival but also as far as quality of life is concerned.     

Cytoreductive surgery in primary advanced epithelial ovarian cancer

Epithelial ovarian cancer is one of the most common malignancy and one of the principal causes of death among gynaecological neoplasm. The majority of patients (about 70%) present with an advanced International Federation of Gynaecology and Obstetrics stage disease. The current standard treatment for these patients consists of complete cytoreduction and combined systemic chemotherapy (CT). An increasing proportion of patients undergoing complete cytoreduction to no gross residual disease (RD) is associated with progressively longer overall survival. As a counterpart, some authors hypothesized the improving in survival could be due more to a less diffused initial disease than to an increase in surgical cytoreduction rate. Moreover the biology of the tumor plays an important role in survival benefit of surgery. It’s still undefined how the intrinsic features of the tumor make intra-abdominal implants easier to remove. Adjuvant and hyperthermic intraperitoneal CT could play a decisive role in the coming years as the completeness of macroscopic disease removal increases with advances in surgical techniques and technology. The introduction of neo-adjuvant CT moreover will play a decisive role in the next years Anyway cytoreduction with no macroscopic residual of disease should always be attempted. However the definition of RD is not universal. A unique and definitive definition is needed.     

Foxp3在卵巢上皮性癌组织中的表达及其与预后相关性的研究

目的:探讨Foxp3在卵巢上皮性癌组织中的表达及其与预后的相关性。方法:选取2003年1月至2007年12月在上海交通大学医学院附属仁济医院诊治的卵巢上皮性癌患者的组织标本,用免疫组化法测定Foxp3在卵巢良性上皮性肿瘤、交界性上皮性肿瘤和恶性上皮性肿瘤组织中的表达,并比较卵巢上皮性癌相关的临床指标及病理学因素。结果:Foxp3在卵巢上皮性癌中阳性表达率为56.7%(17/30),显著高于卵巢良性上皮性肿瘤(0%,0/10)和交界性卵巢肿瘤(20%,2/10)(P=0.001,P<0.05)。Foxp3的表达与组织学分级显著相关(P=0.004)。Foxp3(+)与Foxp3(-)患者的生存曲线差异接近统计学差异水平(P=0.057)。结论:Foxp3表达升高与卵巢癌的预后不良存在相关趋势。     

Novel expression of CD11b in epithelial ovarian cancer: Potential therapeutic target

Objective

The objective of this study was to determine the expression, and effect of targeting CD11b with a monoclonal antibody in ovarian cancer cells.

Supracervical hysterectomy in patients with advanced epithelial ovarian cancer

OBJECTIVE: To assess whether supracervical hysterectomy (SCH) is a reasonable alternative to total abdominal hysterectomy in patients with advanced ovarian cancer. METHODS: We reviewed the records of patients with advanced ovarian cancer who underwent a SCH at one institution between 1993 and 2004 and a similar cohort who underwent total abdominal hysterectomy (TAH) at the same institution during the same period. Patients without complete surgical staging done at the institution were excluded. Independent-sample t tests, Fisher exact test, and log rank tests were used for statistical analysis. RESULTS: The study included 47 patients who underwent SCH (mean age, 59.6 years) and 190 who underwent TAH. There were no significant differences between the two groups in age (P=.51), preoperative CA 125 level (P=.55), or receipt of taxane-based and platinum-based chemotherapy (P=.84). Although limited by sample size, there were no significant differences between the two groups in rates of intraoperative complications (4 of 47 in the SCH group, or 8.5%, compared with 7 of 190 in the TAH group, or 3.7%; P=.24), vaginal or cervical recurrence (5 of 47 in the SCH group, or 10.6%, compared with 22 of 190 in the TAH group, or 11.6%; P=1.00), or in progression-free survival (SCH of 1.01 years compared with TAH of 1.19 years; P=.64) or overall survival (SCH of 3.28 years compared with TAH of 3.36 years; P=.12). CONCLUSION: Supracervical hysterectomy may be a reasonable alternative to TAH in patients with advanced ovarian cancer. LEVEL OF EVIDENCE: II.     

Cisplatin-paclitaxel-cyclophosphamide with G-CSF in primary advanced epithelial ovarian cancer

INTRODUCTION: In an attempt to increase survival, we performed a prospective trial of high-dose cisplatin-paclitaxel-cyclophosphamide with granulocyte colony-stimulating factor (G-CSF) for three cycles followed by carboplatin-paclitaxel for three cycles after cytoreduction of primary advanced epithelial ovarian cancer. MATERIALS AND METHODS: Thirty consecutive women with Stage 3 or 4 invasive primary epithelial ovarian cancer were treated with cytoreductive surgery. Postoperatively patients received 100 mg/m(2) of cisplatin, 200 mg/m(2) of paclitaxel, and 500 mg/m(2) of cyclophosphamide IV q 21 days x 3 cycles with 300 microg of G-CSF daily x5 beginning the first day following chemotherapy. This was followed by carboplatin AUC-5 and 135 mg/m(2) of paclitaxel IV q 21 days x3. All administration was outpatient and paclitaxel was administered over 3 h. RESULTS: Eighty percent of tumors were Stage 3C, 77% were serous, and 60% were Grade 3. Maximum cytoreduction to <2 cm was performed in 96%. Median follow-up is 30 months. Sixty-three percent of patients developed recurrence. Currently 50% of patients are alive with no evidence of disease. Estimated mean survival is 61 months and estimated mean progression-free survival is 29 months. No patient developed thrombocytopenia, neutropenic sepsis, significant neuropathy, or renal toxicity. CONCLUSION: This treatment regimen resulted in minimal toxicity and, following aggressive cytoreduction, produced good progression-free and overall survival.