Prognostic factors of stage IV epithelial ovarian cancer: a multicenter retrospective study

OBJECTIVE: In the present study, we conducted a multicenter retrospective analysis to elucidate the prognostic factors of stage IV epithelial ovarian cancer. METHODS: In November 1999, 24 Japanese institutions received questionnaires regarding stage IV epithelial ovarian cancer patients. Eligibility criteria included all patients with stage IV epithelial ovarian cancer who were surgically confirmed and initially treated in each institution between January 1990 and December 1997. Data were collected regarding age, performance status, tumor histologic subtype, site of metastasis, preoperative CA125, cytoreductive surgery, residual disease after cytoreductive surgery, and response to primary chemotherapy. Survival analysis and comparisons were performed by univariate and multivariate methods. RESULTS: Two hundred twenty-five patients with stage IV ovarian cancer were identified. The median age of the patients was 54 years. The most common site of extraperitoneal disease was malignant pleural effusion (39.6%). Of the 225 patients who underwent an attempt at surgical debulking, 70 (31.1%) were optimally cytoreduced. Most patients received platinum-based combination chemotherapy for primary chemotherapy. In multivariate analysis, performance status, histology, and residual disease after cytoreductive surgery were independent prognostic predictors of outcome. The overall median survival for optimally debulked patients was 32 months compared to 16 months for suboptimally debulked patients (P < 0.0001, hazard ratio: 0.415). CONCLUSION: Optimal surgical debulking, performance status, and histology appear to be important prognostic factors of survival in patients with stage IV epithelial ovarian cancer.     

卵巢上皮性癌复发的处理

目的 探讨影响卵巢上皮性癌复发的因素及处理方法。方法 对１８９例卵巢癌进行回顾性分析,全部手术切除标本均经病理检查证实。结果 １８９例中,复发３１例。其中１９例为我院施行肿瘤细胞减灭术,残留癌灶直径≤２ｃｍ;１２例为外院施行肿瘤细胞减灭术,达到临床愈后因复发转入我院。复发的３１例初次手术中,Ⅰ、Ⅱ期４例（１２．９％）,Ⅲ、Ⅳ期２７例（８７．１％）。其中１０例手术切净者,平均复发时间为１７．２个月;     

肺耐药蛋白在上皮性卵巢癌中的表达及临床意义

目的 :探讨肺耐药蛋白 (lungresistanceprotein ,LRP)在原发性上皮性卵巢癌(POEC)组织中的表达及其临床意义。方法 :采用免疫组化SP法检测POEC 6 4例、经化疗后二次手术癌组织 2 3例以及良性卵巢肿瘤 2 1例石蜡标本中LRP的表达 ,并分析 6 4例POEC患者的临床病理资料。结果 :6 4例POEC组织中LRP阳性表达 5 3例 ,阳性率82 .8% ;2 3例化疗后癌组织中LRP阳性表达 2 3例 ,阳性率 10 0 % ;2 1例良性卵巢上皮性肿瘤中LRP阳性表达 7例 ,阳性率 33.3%。POEC中LRP的阳性表达率与良性肿瘤中表达率差异有高度显著性 (P <0 .0 1) ;化疗后癌组织中LRP的阳性表达率与初治POEC中的表达率差异有显著性 (P <0 .0 5 )。POEC组织中LRP的表达与患者年龄、组织学类型、细胞分级、临床分期和术后肿瘤残存灶大小无关 (P >0 .0 5 ) ;POEC患者LRP阳性表达组近期化疗疗效明显低于阴性表达组 (P <0 .0 5 ) ;但POEC患者LRP表达与患者术后生存时间无关 (P >0 .0 5 )。结论 :LRP在POEC组织中有较恒定的表达 ,化疗可增加POEC组织LRP表达 ,检测LRP可预测化疗近期疗效 ,指导临床化疗方案的选择。     

Significance of multi-drug-resistant proteins in predicting chemotherapy response and prognosis in epithelial ovarian cancer

OBJECTIVES: To clarify the expression of multi-drug-resistant (MDR) markers, GST-pi, c-Jun, P-glycoprotein (Pgp), and MDR-associated protein (MRP) in epithelial ovarian cancer, and to determine whether their expression is predictive of chemotherapy response and patient prognosis. METHODS: Specimens of 58 epithelial ovarian cancer cases obtained at initial surgery were studied immunohistochemically using antibodies. RESULTS: Overall positive rates in the 58 specimens were 58.6% for GST-pi, 44.8% for c-Jun, 27.6% for Pgp, and 22.4% for MRP. The 5-year disease-free survival rate was 26.0% for patients with MRP-positive tumors and 75.2% for those with MRP-negative tumors. The prognosis for those with MRP-positive tumors was significantly poorer (p < 0.05). Patients with GST-pi-positive tumors had a significantly worse prognosis than those with GST-pi-negative tumors (51.9% vs 79.2%, p < 0.05). Multivariate analysis showed that residual tumors 2 cm or larger and MRP expression were independent prognostic factors for chemotherapy resistance. The relative risk of chemotherapy resistance in a patient with a residual tumor 2 cm or larger, positive MRP, and positive GST-pi was 10.6 times greater than the risk in a patient without these factors. CONCLUSION: MRP and GST-pi expression might be potential predictors of the response to standard chemotherapy in epithelial ovarian cancer. Their expression also might contribute to individualizing clinical trials of postoperative chemotherapy.     

Role of salvage cytoreductive surgery in the treatment of patients with recurrent ovarian cancer after platinum-based chemotherapy

OBJECTIVES: The role of cytoreductive surgery, which is well established in the primary treatment for epithelial ovarian cancer, is controversial in recurrent disease. The aim of this study was to assess the clinical benefit of salvage surgical cytoreduction in patients with recurrent ovarian cancer after platinum-based chemotherapy. METHODS: We conducted a retrospective analysis of 46 patients with recurrent epithelial ovarian cancer treated at our department between 1988 and 2003. Twenty-three patients underwent salvage cytoreductive surgery (cytoreductive group), and the other 23 patients were treated without surgery (control group). RESULTS: Patients in cytoreductive group had a median survival of 41.7 months after recurrence, which was significantly longer than control group (18.8 months; P < 0.01). The duration of stay at home and the period oral intake was preserved were significantly longer in the cytoreductive group. In the cytoreductive group, survival was influenced by the residual disease after surgery (residual tumor diameter, <2 cm vs >2 cm; median survival, 50 months vs 35.2 months; P < 0.05). However, the number of recurrent sites (solitary vs multiple) and the lengths of treatment-free intervals after primary treatment (<6 months vs >6 months) showed no significant influence on survival. CONCLUSIONS: The application of cytoreductive surgery might improve the prognosis of patients with recurrent ovarian cancer if the tumor was resectable. Preserved prognoses of platinum-resistant disease with short treatment-free interval demonstrated in this study suggest that the concept of maximum cytoreduction might be introduced in the treatment of recurrent disease in the future.     

铂类与异环磷酰胺联合化疗治疗卵巢复发癌48例临床分析

目的探索卵巢癌二线化疗方案。方法选择曾接受过肿瘤细胞减灭术及多疗程联合化疗、体检或影像学检查有可测得的肿瘤存在、一个月内无化疗史、未接受过放疗、血象及肝肾功正常、病理证实的卵巢上皮性复发癌患者作为治疗对象。用顺铂或卡铂与异环磷酰胺联合化疗,美施钠解毒。结果４８例病人中无完全缓解者;部分缓解１４例（２９２％）;稳定２２例（４５８％）;无效１２例（２５０％）。不同程度毒副反应病人可以耐受。结论顺铂或卡铂与异环磷酰胺联合化疗可作为卵巢上皮性复发癌补救治疗中的主要手段之一,且副反应病人可以耐受。     

卵巢癌新辅助化疗相关问题

卵巢癌的标准治疗方案是以手术为主,术后辅以化疗。能否实现理想的肿瘤细胞减灭术将直接影响患者的预后。而大多数晚期卵巢癌患者的初次肿瘤细胞减灭术难以达到满意。新辅助化疗可以改善晚期卵巢癌患者的术前状态,缩小癌灶,缓解病情,为手术的实施和理想肿瘤细胞减灭术的完成创造有利条件。     

Cisplatin based combination chemotherapy in the treatment of stage III ovarian epithelial tumors of low malignant potential.

Eleven patients diagnosed with Stage III epithelial ovarian tumors of low malignant potential were treated with a combination of cisplatin and cyslophosphamide with or without doxorubicin following primary cytoreductive surgery. Residual disease after initial cytoreduction was macroscopic in nine patients and not observable in two. Eight of the nine patients with macroscopic residual were assessed by second look laparotomy (one refused the procedure), seven showed tumor and one was found to be a complete responder. Of the two patients with no residual disease, one refused second look operation and one had a negative second look. Our findings plus those of other authors suggest that cisplatin based combination chemotherapy is of limited value in the treatment of metastatic ovarian epithelial tumors of low malignant potential.     

Neoadjuvant chemotherapy for advanced ovarian cancer

Neoadjuvant chemotherapy with cisplatin or carboplatin was administered to 29 patients with advanced ovarian carcinoma prior to their undergoing definitive cytoreductive surgery. Twenty-eight patients had ascites, eight had pleural effusion, and 16 had extensive upper abdominal disease on computerized tomography scan. The CA125 response to neoadjuvant chemotherapy was highly predictive of survival ( P <0.0005). A 2-log decrease in CA125 prior to surgery resulted in a median survival of 37 months, while patients with less than a 1-log response in CA125 had a survival of 18 months. Bowel resection after neoadjuvant chemotherapy did not benefit patients, as their survival (17 months) was identical to that of patients who were nonresectable and did not undergo any cytoreductive surgery.
Neoadjuvant chemotherapy offers patients with suboptimal ovarian cancer the same survival as primary cytoreductive surgery with interval debulking, yet with only one operative procedure.     

CA 125 regression: a model for epithelial ovarian cancer response

The rate of decline of CA 125 in effectively treated epithelial ovarian cancer is described by the exponential regression curve CA 125 = EXP [i - s (days after surgery)]. In this equation i, the y-axis intercept, measures initial tumor burden whereas s, the slope of the regression curve, is determined by the extent of cytoreductive surgery and the subsequent response to chemotherapy. Departure from the regression curve uniformly results in progressive disease. In patients whose cancers had been completely removed, we calculated the mean half-life of CA 125 to be 10.4 days (range 4 to 21). In this case s = 0.0835 and characterizes the ideal regression rate. The model predicts that high-dose cisplatin chemotherapy (s = 0.0671) is more effective than low-dose cisplatin (s = 0.0380) (p less than 0.03) in eliminating residual cancer. Because s can be calculated within 2 to 3 months of treatment and then compared with s for the ideal regression curve and with the values of s reported for standard chemotherapy, evaluation of any new treatment protocol can be facilitated with this method.     

Can optimal primary cytoreduction be predicted in advanced stage epithelial ovarian cancer? Role of preoperative serum CA-125 level

The aim of this study was to determine the ability of preoperative serum CA-125 levels to predict optimal cytoreduction in patients with stage III epithelial ovarian cancer. A retrospective review was made of the records of 40 patients with FIGO stage III ovarian carcinoma who underwent primary cytoreductive surgery. A receiver operating characteristic (ROC) curve was used to determine the most useful CA-125 level in predicting optimal versus suboptimal tumour cytoreduction. Twenty-two (55%) patients were optimally cytoreduced (residual disease 500 U/ml. At this threshold, preoperative serum CA-125 level was able to predict optimal versus suboptimal cytoreduction with a sensitivity of 72%, specificity of 73%, positive predictive value of 68%, and negative predictive value of 76%. In the management of patients with advanced epithelial ovarian carcinoma, preoperative serum CA-125 level may help to predict optimal primary cytoreduction and to identify candidates for alternative approaches other than traditional primary cytoreductive surgery, such as neoadjuvant chemotherapy.     

Secondary cytoreductive surgery for isolated nodal recurrence in patients with epithelial ovarian cancer

OBJECTIVES: To evaluate the feasibility and associated survival outcome of secondary cytoreductive surgery in patients with isolated lymph node recurrence of epithelial ovarian cancer. METHODS: Twenty-five patients with epithelial ovarian cancer who underwent secondary cytoreductive surgery for isolated lymph node recurrence were identified from tumor registry databases. Demographic, diagnostic, operative, pathologic, and follow-up data were abstracted retrospectively. Overall survival was calculated using the Kaplan-Meier method. RESULTS: The median age at time of primary surgery for ovarian cancer was 55 years; 72% of patients had FIGO III/IV disease, and all had high-grade tumors. All patients received platinum-based chemotherapy following primary surgery. The median time from completion of primary chemotherapy to nodal recurrence surgery was 16 months (range=6 to 40 months). The distribution of nodal involvement was pelvic=12% (n=3), para-aortic=60% (n=15), inguinal=20% (n=5), peri-cardiac=4% (n=1), and pelvic plus para-aortic=4% (n=1). The maximal nodal tumor diameter ranged from 1.5 cm to 14 cm, with a median of 3.0 cm. Optimal secondary cytoreductive surgery (residual disease 相似文献   

舌下含服硝酸甘油倾斜试验诊断儿童血管迷走性晕厥的价值

目的 探讨舌下含服硝酸甘油倾斜试验(SNHUT)对儿童血管迷走性晕厥(VVS)的诊断价值。 方法 2001年3月至2005年5月在中南大学湘雅二医院儿童晕厥专科就诊或住院的不明原因晕厥(UPS)患儿143例，年龄4~18(12.10±3.03)岁，男58例，女85例。电动倾斜床直立倾斜70°行基础直立倾斜试验(BHUT)，并对其阴性者中的64例在同一角度直接给予舌下含服硝酸甘油片0.2mg，再次评价试验结果。用SPSS 11.0软件进行微机统计学处理。 结果 (1)BHUT阳性率29.4%(42/143)，其中女性占73.8%(31/42)；SNHUT 64例，阳性44例，阳性率为68.7%。SNHUT显著地提高了VVS的检出率。(2)出现阳性结果的时间：BHUT为(21.31±13.24)min，SNHUT为(5.41±4.23)min。(3)反应类型：BHUT及SNHUT阳性患儿共86例，血管抑制型83.7%(72/86)，女性占53.5%(46/86)；心脏抑制型7.0%(6/86)，均为女性；混合型9.3%(8/86)，女性占62.5%(5/8)。(4)副反应：舌下含服硝酸甘油64例，未见明显不耐受现象或其他副反应。 结论SNHUT能提高儿童VVS诊断阳性率，副反应小，使用方便，可在儿科临床推广。     

NLR、PLR联合CA125对上皮性卵巢癌诊断及预后评估的研究

目的 探讨中性粒细胞计数/淋巴细胞计数(NLR)、血小板计数/淋巴细胞计数(PLR)联合CA125对上皮性卵巢癌诊断及预后评估的意义.方法 收集青岛大学附属医院2010年1月至2015年12月收治的236例卵巢上皮性癌及100例卵巢良性肿瘤的病例资料.通过ROC分析,得出NLR、PLR联合CA125对诊断上皮性卵巢癌的...     

Secondary cytoreductive surgery in epithelial ovarian cancer: nonresponders to first-line therapy

Thirty-three patients with progressive or stable epithelial ovarian cancer who underwent secondary tumor-reductive surgery at the University of Texas M. D. Anderson Cancer Center were retrospectively studied. All patients had primary cytoreductive surgery followed by chemotherapy. Lack of response to chemotherapy was clinically documented preoperatively. The tumors of 55% of the patients were secondarily cytoreduced to a greatest diameter of less than 2 cm. Sixty-six percent of the patients required bowel resection. Operative morbidity occurred in 24% of patients, mostly in those with bowel resection. Overall, median survival after secondary surgery was 9.4 months. For patients with residual tumor less than 1 cm, median survival after secondary surgery was 19.5 months, compared with 8.3 months for patients with residual tumor of 1 cm or more (P less than 0.004). Patients with an interval between primary cytoreductive effort and secondary surgery of less than 12 months survived a median of 7.3 months, compared with an 18.3-month median survival for patients with an interval of 12 months or more (P less than 0.004). The present study provided no evidence that secondary surgery is of significant benefit in most patients who have progressive disease during chemotherapeutic treatment of epithelial ovarian cancer.     

Intraperitoneal cisplatin-based chemotherapy vs. intravenous cisplatin-based chemotherapy for stage III optimally cytoreduced epithelial ovarian cancer.

OBJECTIVE: To compare the survival between intraperitoneal cisplatin-based chemotherapy (IPCT) and intravenous cisplatin-based chemotherapy (IVCT) in stage III epithelial ovarian cancer with minimal residual disease (<1 cm) after primary debulking surgery. METHOD: One hundred and thirty-two patients with stage III epithelial ovarian cancer after optimal primary debulking surgery with minimal residual disease between April 1990 and March 1995 were entered into a randomized clinical trial in which IPCT or IVCT was administered at 3-week intervals. Patients in the IPCT arm received cisplatin-based (100 mg/m(2)) intraperitoneal chemotherapy. Patients in the IVCT arm received cisplatin-based (50 mg/m(2)) intravenous chemotherapy. The tumor response was assessed every 3 months. The hematological toxicity using the South West Oncology Group (SWOG) toxicity criteria was assessed. Catheter complications associated with intraperitoneal chemotherapy were also analyzed. RESULT: The estimated median survival in the IPCT group was 43 months (95% confidence interval, 34-54) and IVCT group was 48 months (95% confidence interval, 37-59). The hazard ratio of death was not statistically significant between IPCT and IVCT (hazard ratio, 1.13; 95% CI, 0.69-1.86; P=0.317). The frequencies of hematological toxic effects were significantly lower in the IPCT group than in the IVCT group. CONCLUSION: Intravenous and intraperitoneal chemotherapy are associated with equivalent survival in patients with minimal residual stage III epithelial ovarian cancer after optimal cytoreductive surgery.     

Impact of second look laparotomy and secondary cytoreductive surgery at second-look laparotomy in ovarian cancer patients

OBJECTIVE: Currently, no prospective study supports or refutes the value of secondary cytoreductive surgery in patients with ovarian cancer. We therefore reviewed the surgical data of patients who underwent second-look laparotomy (SLL) with or without secondary cytoreductive surgery at our department. METHODS: Analysis is based on the data of 179 patients who had FIGO stage II (suboptimally staged), stage III or IV ovarian cancer, who received a platinum-based first-line chemotherapy, who were clinically considered to be tumor-free or had at least a clinically partial response to first-line chemotherapy, and who underwent SLL. In patients with macroscopic tumor the diagnostic SLL was followed by a secondary cytoreductive surgery in order to remove as much tumor as possible. Patients with a positive SLL were given second-line chemotherapy. Survival from SLL until death was considered the primary statistical endpoint. RESULTS: In 78 out of 179 (43.5%) a negative SLL could be confirmed pathologically. Patients with negative findings, with microscopic, and macroscopic disease at SLL had a median survival of 66.6, 57.2, and 19.0 months, respectively (p=0.0001). In patients who underwent a secondary cytoreductive operation and in whom residual tumor was none, less than 2 cm, or more than 2 cm, the median survival was 22.9, 17.8, and 15.5 months, respectively (p=0.325). CONCLUSIONS: The presence of macroscopic tumor at SLL is an adverse prognostic factor whereas the role of secondary cytoreductive surgery at SLL appears to be limited in the routine management of ovarian cancer patients.     

Effect of cellular DNA content on the prognosis of epithelial ovarian cancers

OBJECTIVE: To assess the cellular DNA status of epithelial ovarian cancers with regard to clinicopathological findings and its effect on prognosis. MATERIALS AND METHODS: Twenty-six consecutive patients with a diagnosis of epithelial ovarian cancer who had been treated by primary surgery and six courses of platinum-based chemotherapy were enrolled in this study. Second-look laparotomy (SLL) was performed in all cases following confirmation of the clinical remission state. Surgical stage, tumor grade, initial tumor volume, residual tumor volume, histopathologic differentiation, and SLL findings were analyzed in correlation with DNA ploidy and DNA index. DNA analysis was performed via DNA flow cytometry through paraffin-embedded tissue specimens. RESULTS: Of 26 patients, flow cytometric studies revealed 16 aneuploidy cases (61.5%). DNA index values ranged from 1.1 to 1.82 (average 1.29 +/- 0.28). The flow cytometry coefficient of variation mean value was set to 6.7. Taking the cutoff value of 1.2 for DNA indices, a fairly good correlation was detected between DNA ploidy and DNA indices (p < 0.001). The aneuploidy incidence was found to be high in advanced and poorly differentiated tumors (p < 0.05). There was statistically more residual tumor volume in aneuploid tumors during primary cytoreductive surgery and also higher recurrence rates following six courses of chemotherapy compared with diploid tumors (p < 0.05). No significant correlation was detected between the histopathologic subtypes and tumor volume (p > 0.05). Residual tumor volumes were larger in cases with DNA indices of 1.2 yielding higher residual tumor volume following surgery and being in good correlation with SLL results (p < 0.05). The mean survival rates of cases with aneuploid tumor and a DNA index of >1.2 were low compared to those with diploid tumors and DNA indices of <1.2 tumors (p < 0.05). CONCLUSION: DNA ploidy and DNA indices are important prognosticators for malignant epithelial ovarian tumors. They should be evaluated together with the patient's clinical status and other prognostic factors.     

Tumor-associated antigen Ca 125 before and during the treatment of ovarian carcinoma

Serum concentrations of Ca 125, a tumor-associated antigen of epithelial ovarian cancer, were measured in 29 ovarian cancer patients before cytoreductive surgery and in 112 patients during and after treatment. Ca 125 levels were increased (greater than 30 IU/mL) in 89.8% of patients with clinically demonstrable ovarian tumors and were negative in 92.1% of clinically disease-free patients. Low levels of Ca 125 were associated with early clinical stages or a minimal tumor burden, and predicted a successful response to treatment and a low recurrence rate. High values indicated advanced disease and a poor response to cytotoxic chemotherapy. In 77% of patients the operation was explorative, with a preoperative Ca 125 level higher than 1000 IU/mL, whereas all the patients with values less than 100 IU/mL could be operated radically. Serum levels of Ca 125 were increased in similar frequency in epithelial, sex cord, and germ cell ovarian malignancies. The assay of Ca 125 seems to be a reliable noninvasive method for monitoring the presence and clinical behavior of ovarian cancer. Preoperative values have prognostic significance in predicting operability and response to chemotherapy.     

Drug sensitivity-related benefit of systematic lymphadenectomy during cytoreductive surgery in optimally debulked stages IIIc and IV ovarian cancer

OBJECTIVE: The purpose of this study is to assess the survival experience following systematic lymphadenectomy (LNX) in conjunction with primary but optimal cytoreductive surgery in advanced epithelial ovarian cancer (OC) patients when followed by intensive chemotherapy. METHODS: This is a retrospective analysis of all women with OC who were treated in our institution between 1992 and 2000. A total of 98 patients with stages IIIc-IV of OC underwent primary cytoreductive surgery which was 'optimal' (<1 cm residual disease). All patients subsequently received postoperative platinum-containing chemotherapy. Group I, consisting of 51 patients underwent LNX; Group II, consisting of 47 patients did not undergo LNX. The percentage of patients failing to respond to chemotherapy in each group was similar. Each group had statistically equivalent age, stage, regimens of chemotherapy performed, and all other known prognostic factors. RESULTS: No survival benefit could be seen in platinum-sensitive patients. However, in patients who failed to respond to chemotherapy, the 2-year progression-free survival (PFS) (42.8% vs. 14.3%) and overall survival (OS) (51.2% vs. 28.8%) was quite different. LNX significantly improved those of drug-resistant patients when optimal cytoreductive surgery was performed [P = 0.008, risk ratio (rr) = 2.675, 95% confidence interval (CI) = 1.251-5.724]. Cox's proportional analysis shows that LNX was one of the three most significant covariate with the tumor grade and the number of postoperative residual lesions. CONCLUSIONS: The results show that LNX might be of benefit in patients who have optimal primary cytoreductive surgery and who do not respond to platinum-based chemotherapy.