Treatment of recurrent and persistent germ cell tumors with cisplatin, vinblastine, and bleomycin

Four patients were treated with vinblastine, cisplatin, and bleomycin for recurrent or persistent germ cell tumors. In all patients a clinical response was achieved. In 2 patients complete response was attained and they are free of disease following second-look laparotomy. One had a mixed germ cell tumor that persisted as dysgerminoma following primary chemotherapy. The other was a true hermaphrodite with pure dysgerminoma. In patients with endodermal sinus tumor transient response was achieved, but the tumors recurred and the patients died within 6 months.     

Good pregnancy outcome after prenatal exposure to bleomycin, etoposide and cisplatin for ovarian immature teratoma: a case report and literature review

Aim The administration of bleomycin plus etoposide and cisplatin during pregnancy is rare. Materials and methods We describe a case with good pregnancy outcome after exposure to these chemotherapeutic agents at the third trimester of pregnancy. Results and discussion A pregnant woman with stage IIIc immature teratoma underwent surgical staging, and received two cycles of bleomycin, etoposide and cisplatin from the 29th week of pregnancy until delivery. The patient did not have any evidence of recurrence of ovarian cancer for 1.5 years. Her infant did not have any evidence of minor or major malformations, and showed normal neurological development during 1.5 years of follow-up.     

Outcome and prognostic factors in ovarian germ cell malignancies

OBJECTIVES: This study was undertaken to investigate the outcome and prognostic factors in patients with ovarian germ cell malignancies (OGCMs). METHODS: A total of 93 patients with OGCMs were retrospectively reviewed, among whom 84 patients had primary treatment at Chang Gung Memorial Hospital (CGMH) between 1984 and 2003. The other nine patients were primarily treated outside and referred for follow-up (n = 1), adjuvant chemotherapy (n = 4), or salvage therapy after recurrence (n = 4). The clinicopathological and treatment-related characteristics were analyzed for association with the occurrence of tumor persistence/recurrence or death. RESULTS: Of the study patients, 32 had dysgerminoma (DSG), 29 immature teratoma (IMT), 23 endodermal sinus tumor, 7 mixed germ cell tumors, and 1 each had choriocarcinoma and embryonal carcinoma. The median follow-up of survivors was 66 months (range, 12-236 months). The median time to recurrence or progression was 8 months. There were 11 treatment failures with 6 died of cancer. The 5-year survival rate was 97.4% for those primarily treated at CGMH. Histology (DSG/IMT versus non-DSG/IMT) (P < 0.0001) and International Federation of Gynecology and Obstetrics stage (P = 0.001) were significantly associated with treatment failure, while histology (P = 0.0004), salvage high-dose chemotherapy (HD-CT) after primary chemotherapy failed (P = 0.0405), and residual tumor after salvage surgery (P = 0.0014) were significant prognostic factors for overall survival. CONCLUSIONS: Prognosis of OGCMs is excellent if managed with standard treatment initially. Aggressive HD-CT with salvage surgery needs to be applied for recurrent/persistent disease after primary chemotherapy.     

The significance of comprehensive staging surgery in malignant ovarian germ cell tumors

Objective

To evaluate the clinical significance of fertility-preserving comprehensive staging surgery (CSS) in the treatment of malignant ovarian germ cell tumors (MOGCTs).

Methods

A total of 92 cases of MOGCTs were retrospectively reviewed.

Results

Forty-six patients (50%) received CSS, which includes ipsilateral adnexectomy + omentectomy + retroperitoneal lymphadenectomy (appendectomy and multiple biopsies as required). Forty-six patients (50%) received USO, which includes ipsilateral adnexectomy + clinical intraoperative evaluation (including retroperitoneal lymph nodes, great omentum, peritoneal, and contralateral ovary), biopsy of suspicious sites, and excision of all visible lesions. The mean operation time (177.0 vs. 114.8 min; p < 0.0001) and the mean intraoperative blood loss (499.1 ml vs. 112.9 ml; p = 0.04) were significantly higher in the CSS group compared to those in the USO group. The complication rate (17.4% vs 0%, p = 0.003), the relapse rate (10.9% vs 2.2%, p = 0.102) and the mortality rate (4.3% vs 2.2%, p = 0.500) were higher in the CSS group compared to those in the USO group. The difference in complication rate was statistically significant. The overall 5 year survival rates were 92% and 97% in the CSS and USO groups, respectively (p = 0.575). Tumor-free survival rates at 5 years were 87% and 97% in the CSS and USO groups, respectively (p = 0.115).

Conclusions

The benefit of fertility-preserving CSS to MOGCT patients was not greater than that of USO. It is safer and more effective to perform ipsilateral adnexectomy + clinical intraoperative exploration surgery (including retroperitoneal lymph nodes, great omentum, peritoneal, and contralateral ovary), biopsy of suspicious sites, excision of all visible lesions, and adjuvant chemotherapy.     

Immunohistochemical differentiation between ovarian granulosa cell tumors and ovarian carcinomas

Summary Differential diagnosis is a major problem in histopathology of ovarian tumors. Difficulties may arise if the tumor is a poorly differentiated carcinoma or a granulosa cell tumor of the sarcomatoid type. It was the aim of the present study to evaluate the usefulness of immunohistochemistry in differentiating between granulosa cell tumors of the ovary and ovarian carcinomas. We investigated 56 ovarian malignancies (13 granulosa cell tumors, 17 serous, 14 mucinous and 12 poorly differentiated carcinomas) and performed immunohistochemical detection of Vimentin, Keratin, CA125, CA19-9, CEA, S100 and Ber-EP4. Expression of Vimentin was highest and expression of Keratin was lowest in granulosa cell tumors in contrast to carcinomas. CA125 and CA19-9 were not expressed in granulosa cell tumors, whereas the detection rate in carcinomas (except for CA125 in mucinous carcinomas) was high. CEA, S100 and Ber-EP4 do not seem to be useful markers in differential diagnosis. A marker profile of Vimentin, Keratin, CA125 and CA19-9 allows a quite strict differentiation between poorly differentiated ovarian carcinomas and granulosa cell tumors of the ovary.     

Quality of life in long-term survivors of ovarian germ cell tumors: a Gynecologic Oncology Group study

PURPOSE: This report describes the strength and significance of the association between antecedent and mediating variables across four categories of quality of life (QOL) outcomes in 132 disease free women with ovarian germ cell survivors. METHODS: Survivors (n=132) participated in a mailed questionnaire and computer-assisted telephone survey. Participants in four prospective GOG protocols were contacted their treating physician for verbal consent to be approached by investigators at the Indiana University Cancer Center about a quality of life study. Similar patients treated at the MD Anderson Cancer Center were also included. If women verbally consented after being contacted by investigators at Indiana University, an informed consent and questionnaire packet was sent via mail. After return of the written informed consent and background questionnaire, a trained research assistant scheduled a computer-assisted interview to complete data collection. RESULTS: Median follow-up from diagnosis was 10.2 years. Mediating variables of self-efficacy or social support played a significant role (p=0.05 to p=0.001) in all four QOL categories: physical functioning, psychological functioning, sexual functioning, and spiritual functioning. Being a younger age at diagnosis and married were positively related to sexual functioning (p=0.05). Menstrual and gynecological symptoms were inversely related. IMPLICATIONS: Results indicate that clinicians may want to be especially sensitive to identifying a survivor's social support and confidence (self efficacy) in handling issues evolving from treatment since these skills may be related to overall quality of life outcomes.     

卵巢恶性生殖细胞肿瘤保守治疗探讨

目的 探讨卵巢恶性生殖细胞肿瘤（MOGCT）保守治疗对患者存活率、月经和生育功能的影响.方法 1987年1月至2004年10月对天津医科大学总医院妇科共收治MOGCT患者50例中的22例行保守手术,21例行广泛性切除手术,7例行姑息手术,比较3种术式患者的存活率.行保守手术和辅助化疗并存活的MOGCT患者17例（研究组）,随机抽取同期因成熟型畸胎瘤行单侧附件切除术的未绝经患者35例（对照组）与之对照,比较两组治疗后的月经和生育功能.结果 MOGCT占卵巢恶性肿瘤的9.35%,广泛手术和保守手术的存活率分别为74.97%和43.85%（P＞0.05）;研究组和对照组月经紊乱的发生率分别为26.32%和5.71%（P＜0.05）,两组妊娠率分别为83.33%和81.25%,分娩率分别为83.33%和81.25%,均无统计学意义（P＞0.05）.结论 保守手术和辅助化疗对有生育要求的MOGCT患者是安全、有效的,在不影响存活率的前提下,对月经和生育功能无影响.     

复发及未控卵巢恶性生殖细胞肿瘤的治疗

目的 探讨复发及未控的卵巢恶性生殖细胞肿瘤的治疗方法及预后.方法 回顾性分析北京协和医院自1983-2008年收治的复发及未控的卵巢恶性乍殖细胞肿瘤患者17例,总结其初次治疗情况(手术和化疗)及未控或复发后的治疗情况及预后.结果 17例患者均接受了肿瘤切除手术,其中只有4例初次手术时可以明确分期情况.除1例在本院进行初次治疗的患者接受了规范化疗(为初治后复发患者)外.其余l6例在外院进行治疗的患者均未经规范的化疗(均为初治后未控的患者),结果在初次手术后1～8个月再次发现肿瘤生长.有15例患者接受了再次肿瘤切除手术,术后进行了及时规范的化疗.8例患者治疗成功,随诊期间未见肿瘸复发;5例因各种原因放弃治疗;4例失访.结论 卵巢恶性生殖细胞肿瘤规范的初次治疗很重要,即使对于复发及未控的肿瘤,仍应积极进行肿瘤细胞减灭术,术后采用规范的化疗,仍有使肿瘤治愈的可能.     

The activity of taxanes compared with bleomycin, etoposide, and cisplatin in the treatment of sex cord-stromal ovarian tumors

OBJECTIVE: We compared the efficacy and side effects of taxanes, with or without platinum, to bleomycin, etoposide, and cisplatin (BEP) in treating sex cord-stromal ovarian tumors. METHODS: We conducted a retrospective review of all patients with sex cord-stromal ovarian tumors seen at our institution from 1985 to 2002. Eligible patients were those who underwent pathologic confirmation, clinical evaluation, and treatment with a taxane or BEP for initial or recurrent disease. RESULTS: Of 222 patients identified, 21 received BEP for new (n = 11) or recurrent disease (n = 10); 44 received a taxane during 48 treatment episodes (four patients on two occasions each) for new (n = 11) or recurrent disease (n = 37). Newly diagnosed patients treated with BEP vs. taxanes had no significant difference in response rate (Fisher's exact test, P = 1), progression-free survival (PFS) (log-rank test, P = 0.213), or overall survival (log-rank test, P = 0.994). Among patients treated for recurrent measurable disease, the response rate was higher for BEP-treated (71%) than for taxane-treated patients (37%), but this was not statistically significant. In all patients treated for recurrent disease, there was no significant difference in failure to progress at chemotherapy completion between BEP- (70%) and taxane-treated patients (62%) or in median PFS (11.2 vs. 7.2 months). The presence of platinum in taxane-containing regimens correlated with response. Taxane-related side effects included neutropenia (n = 6), anemia (n = 1), thrombocytopenia (n = 1), myelodysplasia (n = 1), and hypersensitivity (n = 1). BEP-related side effects included pulmonary fibrosis (n = 3) and neutropenia (n = 2). CONCLUSIONS: Taxanes demonstrated activity against sex cord-stromal tumors of the ovary and may be less toxic than BEP. Taxane and platinum combination chemotherapy warrants further investigation in this disease.     

卵巢恶性生殖细胞肿瘤合并肺转移15例临床分析

目的 探讨卵巢恶性生殖细胞肿瘤(MOGCT)合并肺转移的临床特点、诊断、出现肺转移时间、治疗及预后.方法 对北京协和医院1982年1月至2010年12月收治的15例MOGCT合并有肺转移患者的临床资料进行回顾性分析.结果(1)临床特点:患者平均发病年龄为(23±11)岁(6 ～48岁).首发临床表现以腹部疼痛和不规则阴道流血为主,分别为8、4例.原发灶位于卵巢左、右侧者分别为8、6例,双侧者1例.转移灶仅为肺者12例,其他3例为多部位转移.(2)诊断:15例患者中,单纯性卵巢非妊娠性绒毛膜癌(绒癌;NGOC)9例,含有绒癌成分的卵巢混合性生殖细胞肿瘤3例(包括卵巢成熟性畸胎瘤合并绒癌1例、卵黄瘤为主伴绒癌及胚胎癌成分1例、绒癌伴无性细胞瘤1例),不含绒癌成分的卵巢恶性生殖细胞肿瘤3例(包括内胚窦瘤2例、未成熟性畸胎瘤1例).其中,仅1例于术前明确诊断.(3)出现肺转移时间:12例NGOC或含绒癌成分的混合性生殖细胞肿瘤患者中,11例在初始治疗的过程中即出现肺转移,1例为肿瘤复发后出现肺转移;3例不含绒癌成分的卵巢恶性生殖细胞肿瘤患者,均为肿瘤复发后在疾病晚期出现肺转移.(4)治疗:15例MOGCT合并有肺转移患者均采用手术联合化疗的综合治疗,平均化疗疗程数为16个(5 ～ 43个).(5)预后:10例(10/15)完全缓解,其病理类型均为NGOC或含绒癌成分的混合性生殖细胞肿瘤;3例患者在治疗过程中病情进展死亡(1例NGOC,1例内胚窦瘤,1例未成熟性畸胎瘤),2例肿瘤进展(1例NGOC,1例内胚窦瘤)放弃治疗后失访.结论 MOGCT发生肺转移以含绒癌成分者多见.MOGCT合并肺转移患者给予手术联合化疗的结合治疗,多数可获完全缓解,病理类型为NGOC或是含绒癌成分的混合生殖细胞肿瘤肺转移患者的预后远较其他类型的恶性生殖细胞肿瘤合并肺转移者为好.     

The role of preoperative serum cancer antigen 125 in malignant ovarian germ cell tumors

Objective

To determine the role of preoperative serum cancer antigen 125 (CA 125) in malignant ovarian germ cell tumors (MOGCTs).

复发性耐药性卵巢恶性生殖细胞肿瘤的治疗

恶性生殖细胞肿瘤治疗关键是规范化,包括手术切除肿瘤、手术病理分期、术后规范化疗,强调及时、足量、正规,可争取90%以上甚至100%的持续缓解率。初次化疗不规范,病情可能持续不缓解或复发。对于复发性恶性生殖细胞肿瘤,再次肿瘤细胞减灭术有减轻瘤负荷的作用,为术后的化疗奠定基础。复发性卵巢恶性生殖细胞肿瘤术后的二线化疗也至关重要。化疗药物应个体化,化疗的疗程数也强调个体化,有阳性肿瘤标志物的患者治疗应持续至肿瘤标志物降至正常后2个疗程。无阳性的肿瘤标志物的患者治疗应持续4~6个疗程。无性生殖细胞瘤和未成熟畸胎瘤对再次化疗或手术仍有效,预后好。卵黄囊瘤则效果很差。卵巢胚胎癌及原发绒癌很少见,治疗经验少。     

Prognostic determinants in patients with uterine and ovarian clear cell carcinoma: A SEER analysis

Introduction

The purpose of this study is to analyze and compare the demographics, treatment, and survival rates in patients with uterine clear cell carcinoma (UCCC) and ovarian clear cell carcinoma (OCCC).

Methods

The Surveillance, Epidemiology and End Results (SEER) program data for all 18 registries from 1988 to 2010 was reviewed to identify women with OCCC and UCCC. Demographic and clinical data were compared, and the impact of tumor site on survival was analyzed using the Kaplan–Meier method. Factors predictive of outcome were compared using the Cox proportional hazards model.

Results

The final study group consisted of 5421 women with clear cell histopathology. 3631 (67%) had OCCC and 1790 (33%) had UCCC. The mean age at diagnosis was 56 (± 12) years for women with OCCC and 67.7 (± 12.0) years for UCCC (P < 0.001). Patients with OCCC had a higher rate of late stage disease (38.9% vs. 21.2%; P < 0.001). Over the entire study period, after adjusting for known variables, there was no significant difference in cancer specific mortality between UCCC and OCCC, HR 1.05 (0.92–1.19). In the subset analysis by staging, in women with localized disease there was an improved survival in UCCC compared to OCCC. In contrast, in women with distant disease there was an increased mortality in women with UCCC.

Conclusion

In the entire population, there was no significant difference in cancer related mortality between the groups. However, in women with localized disease, UCCC had improved survival, but increased mortality in distant disease compared to OCCC.     

维生素E琥珀酸酯诱导卵巢癌细胞SKOV3凋亡的研究

目的探讨维生素E琥珀酸酯(Vitamin E Succinate,VES)对人卵巢腺癌细胞系SKOV3的生物学效应及机制.方法依培养基中有无加VES,将培养的SKOV3细胞分为对照组和实验组,通过MTT比色法检测VES对该细胞系杀伤率的影响;通过光学显微镜、透射电镜观察及流式细胞仪分析检测凋亡;利用caspase-3荧光检测探讨VES作用、SKOV3细胞的作用机制.结果VES处理SKOV3细胞后,细胞存活率明显降低,光镜下见明显形态学改变,电镜下见各个时期的凋亡细胞,流式细胞仪测定发现典型的凋亡峰,活性caspase-3荧光强度增加.结论VES能诱导卵巢腺癌SKOV3凋亡并可能通过激活caspase家族实现.     

Multidisciplinary management of malignant ovarian germ cell tumours

Objectives

Malignant ovarian germ cell tumours (MOGCT) are rare cancers of young women. Limited prospective trials exist from which evidence-based management can be developed. This review summarizes the available literature concerning MOGT in order to provide the clinician with information relevant to their multidisciplinary management.

Methods

MEDLINE was searched between 1966 and 2010 for all publications in English where the studied population included women diagnosed with malignant ovarian germ cell tumours.

Results

The majority of patients can be cured with fertility-preserving surgery with or without combination chemotherapy. Long term survival approaches 100% in early stage disease and is approximately 75% in advanced stage disease. Most studies suggest that the treatment has little, if any, effect on future fertility and limited data suggest that there is no adverse effect on the future quality of life.

Conclusion

MOGCTs are rare tumours of young women the majority of which can be successfully treated with fertility-preserving surgery with or without chemotherapy with preservation of reproductive function. Minimisation of chemotherapy in good prognostic groups and improved treatment in resistant and relapsed MOGCT are important goals for the future. Further studies are needed to quantify the late adverse effects of treatment in long term survivors.