Second-look laparotomy in managing epithelial ovarian carcinoma

Fifty-one patients treated for an epithelial ovarian carcinoma underwent a second-look operation (SLO) from August 1979 to December 1984. Previously, an initial laparotomy had been performed for staging and maximum cytoreductive surgery. This was followed by 6 to 12 courses of combination chemotherapy including cisplatin. Findings at SLO and outcome are discussed as regards extent of initial surgery, preoperative assessment and secondary debulking procedure. In this work, the findings at SLO were often predictable, and related to the adequacy of initial surgery and to a clinical complete response. Nevertheless, after incomplete initial cytoreductive surgery, SLO appears the best procedure to assess the status of the peritoneal cavity and the efficacy of chemotherapy. Negative SLO after incomplete initial surgery assessed a complete response rate of 34% induced by the cisplatin-based chemotherapy. Survival rate of patients with a negative SLO was 93% at 3 years, which demonstrated the highly significant value of SLO in prognosis. Conversely, patient survival with positive findings at SLO was very low, whatever resection can be made. As this work and similar studies by others showed that it could improve patient survival, an attempt should be made to a secondary debulk of residual tumor, and it seems interesting to perform further such secondary resections until definite conclusions can be drawn about this procedure.     

Prognostic factors for survival in stage I epithelial ovarian carcinoma

In a retrospective analysis prognostic factors were studied in 204 patients with primary Stage I epithelial ovarian carcinoma (borderline tumors were excluded) treated between 1975 and 1987. Only histologic grade (P = 0.01) and kind of surgery (total abdominal hysterectomy, bilateral salpingo-oophorectomy +/- omentectomy versus unilateral salpingo-oophorectomy, P = 0.02) were found to have a significant influence on survival prognosis (Cox model). All other factors (age, the International Federation of Gynecology and Obstetrics [FIGO] stage, integrity of the capsule, unilaterality versus bilaterality, and histology) were of no prognostic importance. Unilateral salpingo-oophorectomy without any additional staging reduces five-year survival probability (62% versus 84%). Therefore this kind of operation should be abandoned. Furthermore, histologic grade should be a stratification criterion in studies, which will be necessary for proving the value of adjuvant therapy in Stage I epithelial ovarian carcinoma.     

Second-look laparotomy for epithelial ovarian cancer: A reappraisal

Although second-look laparotomy (SSL) has been used in the management of ovarian cancer for over three decades, its current clinical use is limited. On average, over 50% of patients with a clinical complete response are noted to have disease at the time of SLL, emphasizing our lack of accurate noninvasive methods for determining pathologic response. Although findings at SLL have some prognostic significance, there is no definitive evidence that those patients undergoing SLL have improved survival, and even 50% of patients with negative findings at SLL have recurrences. The lack of survival advantage for patients enduring SLL highlights the need to identify consistently effective salvage and consolidation regimens. Few published studies provide definitive evidence regarding efficacy of treatment. Prospective, randomized, controlled trials are needed to evaluate the various therapies available. In general, the performance of SLL should be confined to those patients enrolled in clinical trials.     

卵巢上皮癌的预后影响因素分析

目的:探讨卵巢上皮癌预后的影响因素.方法:回顾分析自2005年1月至2010年12月在陕西省肿瘤医院收治的292例卵巢上皮癌患者的临床资料.采用Kaplan-Meier法分析生存时间,应用Log-rank法进行组别间生存率差异检验,采用OR值对各因素间进行危险度分析.结果:年龄、手术分期、组织学类型、病理分化程度、肿瘤细胞减灭术后残余瘤的大小以及术后化疗疗程数是卵巢上皮癌的预后生存指标.以FIGOⅠ期患者的死亡风险为1,则Ⅱ期、Ⅲ期、Ⅴ期的死亡风险分别为Ⅰ期的3倍、14.7倍、21.8倍;以术后残余瘤直径≤2cm患者的死亡风险为l,则残余瘤直径＞2cm的患者的死亡风险为残余瘤直径≤2cm患者的死亡风险的80.7倍;化疗疗程数＜6疗程的死亡风险为≥6疗程的2.3倍.以高分化患者的死亡风险为l,则中、低分化的死亡风险分别为高分化的2.4倍、3.8倍.结论:FIGO分期,首次肿瘤细胞减灭术后残余瘤的大小、化疗疗程数、病理分化程度是卵巢上皮癌的独立预后因素.因此尽力做到早诊断、早治疗,术后辅以正规、足程的化疗是提高卵巢上皮癌生存率的关键.     

Prognostic factors for overall survival in patients with advanced ovarian carcinoma

Twenty-one pretreatment variables were investigated for prognostic influence on survival in 301 previously untreated patients with ovarian carcinoma, stage IIB-IV. Patients were randomized to sequential combination chemotherapy: cyclophosphamide, doxorubicin, 5-fluorouracil, followed by cisplatin and hexamethylmelamine, or to the 3-drug combination alternating with the 2-drug combination every other month. Median overall survivals were 25 and 22 months, respectively, P greater than 0.4. Based on the results from a Cox multivariate stepwise analysis a subset of independent significant prognostic factors was found to include: residual tumor size, performance status, alkaline phosphatase, number of metastases, histological differentiation grade and type. A prognostic index was calculated for each patient and three prognostic categories of patients were determined. The 3-yr survival rates for patients with low-, intermediate-, and high-risk scores were 62, 31, and 7%, respectively. Multivariate analysis thus contributes further information about the disease, and a knowledge of the distribution of such factors across different trials is important when comparing treatment outcome.     

Second-look laparotomy for stage III epithelial ovarian cancer: rationale and current issues

During the past two decades, the initial treatment of an advanced ovarian malignancy has been generally uniform: it begins with an exploratory laparotomy surgically to remove as much tumor as possible (1) and to stage the cancer (2). For the 70% of patients classified as stages III and IV, surgery is then followed by combination chemotherapy. Although opinions differ as to the optimal regimen, the standard involves a platinum-based program (3), recently also including paclitaxel (4). A second-look laparotomy is often performed in all patients who achieve a clinical complete remission, that is the inability to detect disease by physical examination and non-invasive laboratory tests. This surgical procedure is able to detect clinical disease not apparent on computerized axial tomography (CT scan), ultrasound, magnetic resonance imaging (MRI), serum CA-125 levels or physical examination (5–7). Major questions, however, have arisen around the need for such a procedure, and whether one can justify it in terms of an improved outcome or merely as an assessment of prognosis (8–14). We shall review: (i) the technique; (ii) the rationale; (iii) the results that have been reported from its routine application; and (iv) controversial issues, particularly as they relate to the evolution of therapeutic strategies.     

40岁以下妇女卵巢上皮癌的预后因素

目的探讨40岁以下妇女卵巢上皮癌的预后因素.方法1980年1月-1992年12月本院收治40岁以下妇女卵巢上皮癌86例,回顾性分析有关预后因素.结果40岁以下妇女卵巢上皮癌二年生存率79.07%,五年生存率54.65%.按FICO分期Ⅰ期49例,按细胞学分级G1期41例,4例保留卵巢功能者均无复发.逐步COX模型多因素分析显示其细胞学分级、残留灶大小、手术方式是影响预后的独立因素(P＜0.01);但与40岁以上卵巢癌病例,并无差异(P＞0.05).单因素分析显示其病理类型、FIGO分期、细胞学分级、残留灶大小、手术方式是影响预后的重要因素(P＜0.01).结论40岁以下妇女卵巢上皮癌临床分期早,细胞分化好,预后较好,部分Ⅰa、G1期患者可保留生育功能.     

Prognostic factors associated with long-term survival in previously untreated metastatic renal cell carcinoma.

PURPOSE: To identify prognostic factors (PF) for long-term survival in metastatic renal cell carcinoma (RCC) patients. METHODS: We retrospectively reviewed a metastatic RCC database at the Cleveland Clinic Foundation consisting of 358 previously untreated patients who were enrolled in institutional review board-approved clinical trials of immunotherapy and/or chemotherapy at our institution from 1987 to 2002. In order to identify patient characteristics associated with long-term survival, we compared 226 'short-term' survivors [defined as overall survival (OS) <2 years] with 31 'long-term' survivors (OS >or=5 years). RESULTS: Using logistic regression models, four adverse PF were identified as independent predictors of long-term survival: hemoglobin less than the lower limit of normal, greater than two metastatic sites, involved kidney (left), and Eastern Cooperative Oncology Group (ECOG) performance status (PS). Using the number of poor prognostic features present, three distinct risk groups could be identified. Patients with 0 or 1 adverse prognostic feature present had an observed likelihood of long-term survival of 32% (21/66) compared with 9% (8/91) for patients with two adverse features present and only 1% (1/93) for patients with more than two adverse features. CONCLUSIONS: Independent predictors of long-term survival in previously untreated metastatic RCC include baseline hemoglobin level, number of involved sites, involved kidney, and ECOG PS. Incorporation of these factors into a simple prognostic scoring system enables three distinct groups of patients to be identified.     

Problems with peritoneal cytology in second-look laparotomy performed in patients with epithelial ovarian carcinoma.

BACKGROUND: The recurrence rate of ovarian carcinoma is high even when a second-look laparotomy (SLL) is negative. In the current study, the accuracy of peritoneal cytology as an evaluation method of SLL was examined. METHODS: The positive SLL rate and the diagnostic accuracy of peritoneal cytology were evaluated in 101 patients with epithelial ovarian carcinoma. RESULTS: Twenty-three of the 101 patients (23%) were positive based on SLL. The factors considered to be high risk factors for a positive SLL were advanced disease (Stages III and IV by the International Federation of Gynecology and Obstetrics [FIGO] classification), serous adenocarcinoma, and maximum residual tumor > 2 cm after primary surgery (P < 0.05). Of the 23 patients found to be positive on SLL, peritoneal cytology was positive in 6 patients, in whom the percentage was low (26%). The remaining 17 patients (74%) demonstrated false-negative cytology. Of these 17 patients, the tumor tissues were found to be capsulated completely with connective tissues in all biopsy specimens from 9 patients (53%) and in all but 1 biopsy specimen in 6 patients (35%), together accounting for a capsulation rate of 88%. Conversely, clear exposure of the tumor tissues was observed in at least two biopsy specimens in those patients demonstrating positive cytology (P < 0.01). CONCLUSIONS: Peritoneal cytology in SLL was found to result in a high false-negative rate. One of the reasons for this was considered to be capsulation of the lesions with proliferated connective tissues, which may have been the result of by chemotherapy.     

Prognostic factors in advanced ovarian carcinoma

Nineteen factors were analyzed for prognostic significance in a series of 89 women with advanced (stage III or IV) ovarian carcinoma treated with chemotherapy after initial debulking surgery. Seventy-eight of these women received cyclophosphamide, Adriamycin (Adria Laboratories, Columbus, Ohio), and cisplatin (CAP) treatment, and 11 received cyclophosphamide initially with Adriamycin and cisplatin administered at the time of recurrence. Median survival and remission duration were 25 and 19 months, respectively. Using survival as an end point, significant prognostic factors in univariate analyses included the total residual mass after debulking (P = .0007), largest residual mass after debulking (P = .0008), and stage (P = .0098). Using remission duration as an end point, significant prognostic factors in univariate analyses included total residual mass after debulking (P = .007) and the largest residual mass after debulking (P = .0020). The prognostic variables were then considered as possible predictors of survival in a multivariate analysis using the Cox proportional hazards model resulting in the following expression: lambda i(t)/lambda o(t) = exp(0.5928 (log TRM - 1.8117) + 0.6450 (stage - 0.3827) + 0.6673 (C4 - 0.4198) - 0.8596 (CAP - 0.8642)), where lambda i(t)/lambda o(t) is the risk of dying for a particular patient compared with the average risk of the entire group; log TRM is the log of the volume of the total residual mass in cm3 plus 1.0; stage = 0 if stage III, 1 if stage IV; C4 = 0 if cytologic grade is 1, 2, or 3 and 1 if grade 4; CAP = 0 if treatment is cyclophosphamide and 1 if CAP. Median survival times of patients with relative risk greater than 1 and less than 1 are 43 and 19 months respectively. If this model is confirmed in a prospective study, then it could be used to assign risk and assess treatment options for similar patients at diagnosis.     

A critical reassessment of second-look laparotomy in epithelial ovarian carcinoma

Eighty-eight women with epithelial ovarian carcinoma, treated by first-line chemotherapy, achieved a complete clinical response and underwent second-look laparotomy to assess the true pathologic status of their disease. Persistent tumor was found in 50 patients (57%). Thirty-two of these (36%) had obvious gross tumor, whereas, 16 (18%) had microscopic disease. Thirty-eight patients (43%) had no pathologic evidence of persistent ovarian carcinoma. With a follow-up of 6 to 60 months, 30 of these patients (79%) remain without evidence of recurrence. Multivariate logistic regression analysis revealed three covariates that were independently significant in predicting continued disease-free status. These included: the greatest diameter of the largest residual tumor left at the primary operation; histologic features of the tumor; and the diameter of the largest tumor aggregate found at initial operation. A mathematical model based on the most significant covariates was designed to assess the relative risk of any patient having persistent tumor at second-look laparotomy. A comparison of the predicted to actual outcome revealed a sensitivity of the model of 88%, a specificity of 71%, and an accuracy of 77%. Second-look laparotomy represents the basis on which potentially curative second-line salvage therapy can be initiated. With an increasing period of follow-up and with greater numbers of patients, it can potentially document a complete pathologic response to first-line therapy administered with curative intent, and identify patients for additional, adjunctive therapy, who are at risk of recurrence.     

Prognostic factors of secondary ovarian carcinoma

OBJECTIVE: Although the ovaries are common sites of metastases from a variety of primary neoplasms excluding carcinomas of the genital tract, there were few reports concerning survival and prognostic factors. The objective of this study was to assess the clinical factors affecting survival. METHODS: Fifty-three secondary ovarian carcinomas excluding metastases from genital tract carcinoma were registered by the Tokai Ovarian Tumor Study Group from 1989 to 1999. FIGO staging was set without considering the pathologic findings of the lymph nodes and the primary tumors. RESULTS: Twenty-four patients were stage I, 11 were stage II, 16 were stage III, and 2 were stage IV. There were significant differences in the survival curves between the early stages (I and II) and advanced stages (III and IV). The 5-year survival rate for patients without residual tumors was 39.9%, while all patients with residual tumors after surgery died within 33 months. The most frequent primary tumor was large intestinal carcinoma, and the second was gastric carcinoma. The 5-year survival rate for patients with large intestinal primary tumors was significantly better than that with stomach tumors. Multivariate analysis demonstrated that tumor stage and primary tumor sites were significant prognostic factors. CONCLUSION: FIGO staging without considering lymph node involvement and the primary tumor was a significant prognostic factor, and prognostic factors for primary ovarian carcinomas can be applied to secondary ovarian carcinomas. Furthermore, the primary tumor site was also an important prognostic factor for survival.     

Prognostic factors for surgical outcome and survival in 447 women treated for advanced (FIGO-stages III-IV) epithelial ovarian carcinoma

The objectives of this population-based, retrospective study, was to find predictive factors for surgical outcome and long-term survival in 447 patients with epithelial ovarian cancer in FIGO-stages III-IV treated during 1975-1993. The median overall survival rate of this series was 18 months, the 5-year cancer-specific survival rate was 18%, and the 5-year overall survival rate, 16%. In a logistic regression analysis, type of surgeon was the strongest (P=0.006) predictive factor for surgical outcome after the age of the patient. The optimal debulking rate was 36% for gynecologic oncologists, 29% for general gynecologists, 24% for combined gynecologist and obstetrician with the third level of specialization, and 4% for general surgeons. Optimal debulking (no visible tumor or residual tumor <2 cm) was achieved in 26% of the cases. Predictive factors of the outcome of cytoreduction were FIGO-stage (P=0.007), histological subtype (P=0.016), and tumor grade (P=0.046) in univariate analyses. In a Cox multivariate analysis the most important prognostic factor for overall survival was the amount of residual cancer (P=0.000001) before age, grade and stage. Therefore, to achieve optimal surgical outcome and optimal overall survival rate the primary surgery of advanced ovarian cancer should be performed by gynecologic oncologists or by gynecologists specially trained in gynecologic cancer surgery.     

年轻妇女卵巢上皮细胞癌预后因素分析

目的　探讨年轻妇女卵巢上皮细胞癌的临床特点、生存率和影响预后的因素。方法回顾分析 1985～ 1997年收治的 4 5 5例卵巢上皮细胞癌患者的临床资料。生存率采用Kaplan Meier方法计算 ,利用Cox风险比例回归模型分析比较影响患者预后的独立因素。结果　≤ 4 0岁组92例 ,>4 0岁 36 3例。≤ 4 0岁组早期、高分化、黏液性癌所占比例明显高于 >4 0岁组 ,浆液性癌、腹水、肿瘤残存所占比例低于 >4 0岁患者 ,差异均有显著性 (P <0 .0 5 )。≤ 4 0岁组和 >4 0岁组的 5年生存率分别为 79.5 %和 2 8.2 % ,差异均有极显著性 (P <0 .0 0 1)。单因素分析两组间同一临床分期、组织类型、分级、肿瘤残存情况等显示 ,在相同情况下 ,≤ 4 0岁患者的生存率明显高于 >4 0岁者。多因素分析显示 ,临床分期、肿瘤残存情况和年龄为影响预后的独立因素。结论　≤ 4 0岁的卵巢上皮细胞癌患者 ,其早期、Ⅰ级、黏液性囊腺癌所占比例高 ,肿瘤残存小 ,腹水少 ,总的 5年生存率高。临床分期、肿瘤残存情况、年龄是影响卵巢上皮细胞癌预后的独立因素。     

Prognostic value of human kallikrein 10 expression in epithelial ovarian carcinoma.

PURPOSE: Human kallikrein 10 (hK10; also known as the normal epithelial cell-specific 1 gene and protein) is a secreted serine protease, which belongs to the human kallikrein family. It has been reported that hK10 is down-regulated in breast and prostate cancer cell lines and that it may function as a tumor suppressor. Recently, we developed a highly sensitive and specific immunoassay for hK10 and found that this protein is abundantly expressed in ovarian tissue. In this study, we measured quantitatively hK10 levels in ovarian cancer cytosolic extracts and evaluated the prognostic value of this biomarker in ovarian cancer. EXPERIMENTAL DESIGN: Specimens from eight normal ovarian tissues, eight ovarian tissues with benign disease, and 182 ovarian tumors were investigated. RESULTS: hK10 concentration in ovarian tumor cytosols ranged from 0 to 84 ng/mg of total protein, with a median of 2.6. This median was highly elevated in comparison with normal and benign ovarian tissues (P < 0.001). A cutoff of 1.35 ng/mg was selected to categorize tumors as hK10 high and hK10 low. With chi(2) test and Fisher's exact test, high concentration hK10 was found to be associated with advanced disease stage, serous histological type, suboptimal debulking, and large residual tumor (>1 cm; all P < 0.05). hK10 status was additionally correlated with clinical outcome, including progression-free (PFS) and overall survival (OS) using the Cox model. In univariate analysis, we found that patients with hK10 high tumors were more likely to die and relapse, in comparison with patients with hK10 low tumors (hazards ratios for PFS and OS were 1.93 and 2.42, respectively; P < 0.05). Although this correlation disappeared after the entire patient population was subjected to multivariate analysis, it remained significant in the subgroup of patients with stage III/IV ovarian cancer (hazards ratios for PFS and OS were 1.98 and 2.12, respectively; P < 0.05). CONCLUSIONS: Our results indicate that hK10 is a new, independent, unfavorable prognostic marker, especially for late-stage ovarian cancer.     

Second-look laparotomy in the management of patients after radical surgery for ovarian cancer

BACKGROUND: Radically excised ovarian cancers present an unsolved problemwith regard to the value of routine second-look operation. Thisstudy presents the outcome of second-look operations in an effortto help elucidate this problem PATIENTS AND METHODS: Twenty-eight patients who underwent radical surgery for ovariancancer stage IC-IIIA were given adjuvant chemotherapy with cyclophosphamide500 mg/m² i.v., adriamycin 40 mg/m² i.v. and 5-fluorouracil500 mg/m² i.v., all administered on days 1 and 8 every 4 weeksuntil achievement of a cumulative adriamycin dose of 400 mg/m².It was planned that second-look laparotomy would be performed10-12 months after the primary operation. RESULTS: Four of 28 patients (14.3%) had positive findings at second-looklaparotomy. Two of these 4 patients had only microscopic disease,and after second-line chemotherapy including cisplatin one ofthem is clinically free of tumor 50 months after the primaryoperation. Two of 28 patients had clinical recurrences beforethe planned second-look operation. Four of the 22 patients (18.2%)with negative secondlook operations developed recurrent diseasewithin a median time of 12 months later. The 5-year survivalrate for all 28 patients was 67%. CONCLUSION: Although a small group of patients may benefit from a strategythat includes delayed second-look operation, we conclude thatthis should not be a routine procedure in the management ofpatients who undergo radical surgery for ovarian cancer. ovarian cancer, second-look operation     

124例上颌窦癌预后因素分析

目的探讨上颌窦癌的临床病理特征与预后的关系。方法124例上颌窦癌中放疗40例，手术治疗18例，放疗＋手术治疗66例。生存率计算采用Kaplan-Meier法，生存率差异比较采用Logrank检验，多因素分析采用Cox模型。结果5年总生存率、癌症相关生存率和无进展生存率分别为32.5％、37．4％和27．2％。单因素分析显示，肿瘤位置、病理类型、T分期、淋巴结转移情况、临床分期和治疗方式与癌症相关生存（CSS）和无进展生存（PFS）均有相关性；而年龄仅与CSS相关，而与PFS无关。多因素分析显示，病理类型、T分期、临床分期和治疗方式是影响预后的独立因素。结论T分期和临床分期是影响上颌窦癌预后的重要因素。对113～T4期即使淋巴结阴性上颌窦鳞癌，予以颈部预防性照射也是必要的。上颌窦癌的最佳治疗模式仍有待进一步研究。     

Prognostic factors in epithelial ovarian cancers--clinical significance of morphologic indicators

The main factors influencing prognosis (staging, histologic classification and grading, lymphocyte infiltration etc.) in 110 patients with epithelial ovarian cancers were analysed by life table technique to obtain 5 year cumulative survival rate. Multivariate statistical analysis (Cox Model) was used in 88 patients in order to find out the most important prognostic factor. The results showed that degree of lymphocyte infiltration in the tumor was the most important; the next was clinical factors; moreover, the amount of residual tumor was more significant than staging. Specimen from reoperation revealed less lymphocyte infiltration than that from the first operation. The degree of lymphocyte infiltration as an expression of the local host defence can be used as a good prognostic indicator.     

Prognostic factors in stage IV ovarian carcinoma treated with platinum-based regimens

Eight factors were analyzed for prognostic significance in univariate analyses in a series of 76 women with stage IV ovarian carcinoma treated with combination chemotherapies including cisplatin or carboplatin. The clinical objective and pathologic complete response rates were 51.2% and 27.3%, respectively. Median overall survival and progression-free survival were 15 and 7 months, respectively. No variables reached statistical significance. Trends toward better survival were noted for grades 1 and 2 for the adriamycin-containing regimen. Using progression-free survival as an end point, significant prognostic factors included complete clinical or pathologic response. Our data confirm that the standard approach is unlikely to modify the clinical outcome of stage IV ovarian cancer. New treatment modalities including high-dose-intensity regimens and neo-adjuvant chemotherapy delivered before surgery could improve clinical results. Moreover, biologic characterization of ovarian tumors may provide information to design specifically targeted treatment.