Laparoscopic surgery in the treatment of stage I adult granulosa cells tumors of the ovary: Results from the MITO-9 study

Objective

Surgery represents the mainstay of treatment of stage I adult type granulosa cell tumors of the ovary (AGCTs). Because of the rarity and indolent course of the disease, no prospective trials are available. Open surgery has long been considered the traditional approach; oncological safety of laparoscopy is only supported by small series or case reports. The aim of this study was to compare the oncological outcomes between laparoscopic and open surgery in stage I AGCTs treated within the MITO (Multicenter Italian Trials in Ovarian cancer) Group.

Survival analysis of children with stage II testicular malignant germ cell tumors treated with surgery or surgery combined with adjuvant chemotherapy

For children with stage II testicular malignant germ cell tumors(MGCT), the survival is good with surgery and adjuvant chemotherapy. However, there is limited data on surgical results for cases in which there was no imaging or pathologic evidence of residual tumor, but in which serum tumor markers either increased or failed to normalize after an appropriate period of half-life time post-surgery. To determine the use of chemotherapy for children with stage II germ cell tumors, we analyzed the outcomes(relapse rate and overall survival) of patients who were treated at the Sun Yat-sen University Cancer Center between January 1990 and May 2013. Twenty-four pediatric patients with a median age of 20 months(range, 4 months to 17 years) were enrolled in this study. In 20 cases(83.3%), the tumors had yolk sac histology. For definitive treatment, 21 patients underwent surgery alone, and 3 patients received surgery and adjuvant chemotherapy. No relapse was observed in the 3 patients who received adjuvant chemotherapy, whereas relapse occurred in 16 of the 21 patients(76.2%) treated with surgery alone. There were a total of 2 deaths. Treatment was stopped for 1 patient, who died 3 months later due to the tumor. The other patient achieved complete response after salvage treatment, but developed lung and pelvic metastases 7 months later and died of the tumor after stopping treatment. For children treated with surgery alone and surgery combined with adjuvant chemotherapy, the 3-year event-free survival rates were 23.8% and 100%, respectively(P = 0.042), and the 3-year overall survival rates were 90.5% and 100%, respectively(P = 0.588). These results suggest that adjuvant chemotherapy can help to reduce the recurrence rate and increase the survival rate for patients with stage II germ cell tumors.     

Menstrual and reproductive function after treatment with combination chemotherapy for malignant ovarian germ cell tumors

Forty patients who had been treated for malignant ovarian germ cell tumors completed a questionnaire designed to evaluate their menstrual and reproductive function. All patients met the following eligibility criteria: (1) successful treatment with combination chemotherapy, and (2) retention of a normal contralateral ovary and uterus. Median age at diagnosis was 15 years (range, 6 to 29), and median age at the time of interview was 25.5 years (range, 14 to 40). Patients had received a variety of chemotherapeutic regimens, the most common of which was a combination of vincristine, dactinomycin, and cyclophosphamide (N = 28). Since discontinuation of chemotherapy, one patient remains premenarchal, and 27 patients have maintained regular menses. The other 12 patients have had menstrual difficulties, but in only three were the problems considered to be serious. Of the 16 patients who have attempted to become pregnant since completing chemotherapy, 11 have delivered 22 healthy infants, none of whom had major birth defects. Only one patient has had persistent problems with infertility. In summary, it appears that the majority of patients who receive combination chemotherapy for malignant ovarian germ cell tumors can anticipate normal menstrual function and a reasonable probability of having normal offspring.     

The management of stage I nonseminomatous testicular germ cell tumors

Testicular germ cell tumors represent the most common malignancies in young males; 70% of patients with seminomas and 50% of those with nonseminomatous germ cell tumors (NSGCT) have clinical stage I at diagnosis. Lymphovascular invasion, embryonal-cell carcinoma component, absence of yolk sac histology and MIB1 proliferation rate represent predictors of micrometastatic diseasein stage I NSGCT. Therapeutic options following orchiectomy in patients with stage I NSGCT comprise nerve-sparing retroperitoneal lymph node dissection, surveillance or adjuvant cisplatin-based chemotherapy. All available treatment modalities produce excellent results, with a long-term survival of almost 100%. Consequently, therapy-induced toxicity is an important concern in the management of these patients. An individually tailored approach that takes into account the prognostic factor profile as well as the patient's preferences and their ability to comply with each one of the modalities is the key to the management of stage I testicular cancer.     

DNA copy number changes in malignant ovarian germ cell tumors

Malignant ovarian germ cell tumors (OGCTs) include immature teratomas (ITs), dysgerminomas (DGs), endodermal sinus tumors (ESTs), choriocarcinomas, and embryonal carcinomas. Knowledge about the genetic changes associated with malignant OGCT development is sparse. We therefore analyzed 25 OGCTs (12 DGs, 4 ESTs, and 9 ITs) for gains and losses by comparative genomic hybridization. In total, more gains than losses were observed, and the number of alterations ranged from 0-20 per tumor. The average number of changes among DGs, ESTs, and ITs was 10, 6, and 1.4, respectively. The most common changes in DGs were gains from chromosome arms 1p (33%), 6p (33%), 12p (67%), 12q (75%), 15q (42%), 20q (50%), 21q (67%), and 22q (58%); gains of the whole of chromosomes 7 (42%), 8 (42%), 17 (42%), and 19 (50%); and losses from 13q (58%). Two of three DGs with a gonadoblastoma component showed gains of 3p21 and loss of 5p, whereas none of the nine pure DGs had these changes, suggesting that they might be characteristic either of gonadoblastoma or of DG developing from a gonadoblastoma. Gain of 12p and gain from 1q were seen in three of four ESTs, whereas gains from 3p, 11q, and Xp and loss from 18q were each found in two tumors. Five of the ITs revealed changes (range, 1-4 changes/tumor), with gains from 1p, 16p, 19, and 22q each being found in two tumors. We conclude that ovarian DGs and ESTs seem to develop via the same genetic pathways that are already known for testicular germ cell tumors. On the other hand, ITs do not exhibit gain of 12p and also typically show fewer changes than other malignant OGCTs, indicating that they arise via different pathogenetic mechanisms.     

Sequential combination chemotherapy for malignant germ cell tumors of the ovary

Fourteen patients with malignant ovarian germ cell tumors were treated postoperatively with a short-term, sequential regimen combining cisplatin, vincristine, methotrexate, bleomycin, dactinomycin, cyclophosphamide, etoposide, Adriamycin (Adria Laboratories, Columbus, OH), and vinblastine (POMB/ACE/PAV). Two patients had Stage I disease, Five had Stage II, five had Stage III, and two had Stage IV. The histologic diagnosis was immature teratoma in five cases (two cases were Grade 2 and three cases were Grade 3) endodermal sinus tumor in two cases, dysgerminoma in three cases, and mixed germ cell tumors in four cases. The chemotherapy regimen appeared to be highly effective against all histologic types, including advanced stages, with 12 of 14 (86%) overall sustained remissions. The median duration of treatment was 5 months. The toxicity of the regimen, which contained low total doses of cisplatin and bleomycin, was only moderate. After a median follow-up of 53+ months, 13 patients were alive without evidence of disease. The results and toxicity obtained were compared with those from other currently used regimens. Also, some comments on initial surgery and second-look surgery are given.     

Treatment of malignant ovarian germ cell tumor and sex cord tumors

We outline chemotherapy mainly for malignant ovarian germ cell and sex-cord tumors, based on studies in the literature and our own clinical experiences. With both tumors, PEB treatment is standard adjuvant chemotherapy. With regard to the number of dosage courses, 4 courses are regarded as tolerable after incomplete reduction, and 3 courses as adjuvant treatment after complete extraction. This chemotherapy is effective for preservation of fertility in young patients with malignant ovarian germ cell tumor. In both tumors, some cases show chemotherapy resistance. An effective second-line treatment strategy using a new anticancer agent needs to be established for such cases in the future.     

First-line chemotherapy of non-seminomatous germ cell tumors(NSGCTs)

Germ cell tumors (GCTs) account for the majority of testicular cancer cases occurring in men of young age and are divided into two main histologic groups, seminomas and non-seminomas. The introduction of cisplatin in the treatment of germ cell tumors was a breakthrough, classifying them among curable diseases. The identification of 3 subgroups of patients with non-seminomatous tumors (good-risk, intermediate and poor-risk), with different profiles concerning prognosis and response to treatment, supported clinical trials aiming to assess different treatment strategies and recommend the most effective and less toxic regimens. This review describes the toxic effects of therapy and the efforts aiming to overcome toxicity and improve treatment efficacy, focusing on the trials which form the basis of current standard treatment of non-seminomatous germ cell tumors.     

Orchidectomy alone in stage I nonseminomatous testicular germ cell tumors

Fifty-four patients with Stage I nonseminomatous testicular germ cell tumors (NSTGCT) were treated from 1982 to 1984. In 1982 and 1983, the orchidectomy was followed by an exploratory laparotomy to conclude the dissemination study. In 1984, laparotomy was performed only if indicated. The mean follow-up was 29 months. A relapse occurred in 11 patients (20%). The relapse rate in patients who underwent exploratory laparotomy was as high as that in patients who did not. All patients treated for relapse by chemotherapy and surgery entered a complete remission for at least 1 year. It proved impossible to establish criteria for prediction of a subsequent relapse. Both serum tumor marker assays and roentgenography are important aids in diagnosing a relapse. With careful follow-up of Stage I NSTGCT patients, a wait-and-see attitude can be adopted until a relapse occurs.     

The role of chemotherapy in early-stage (stage I and II) resectable non-small cell lung cancer

For patients with stage I or II non-small cell lung cancer (NSCLC), surgical resection is considered the standard of care. Although surgery achieves long-term survival in many patients, a significant proportion experience locoregional or distant recurrence. Five-year survival rates after resection for stage I and II NSCLC range from 38% (T3 N0) to 67% (T1 N0). Efforts at improving survival for early-stage NSCLC patients have focused on the use of chemotherapy administered postoperatively (adjuvant) or preoperatively (neoadjuvant or induction) to eradicate micrometastatic disease. The majority of trials examining adjuvant chemotherapy have not found a survival benefit. A meta-analysis examining the role of chemotherapy in the treatment of NSCLC found a 5% absolute improvement in 5-year survival associated with the use of adjuvant cisplatin-based chemotherapy (P =.08). Chemotherapy administered before surgery or definitive irradiation has improved survival rates in patients with stage III NSCLC. The role of induction chemotherapy in stage I and II NSCLC is currently under investigation.     

卵巢恶性生殖细胞肿瘤的诊疗研究现况

卵巢恶性生殖细胞肿瘤相对少见,多发生于年轻女性,除无性细胞瘤外其他均为高度恶性。保留生育功能的手术联合有效的化疗方案明显提高了预后,多数患者治疗后能恢复月经周期并正常妊娠,但复发患者的治疗仍是难点。目前我们就卵巢恶性生殖细胞肿瘤近年来诊断和治疗现况作一阐述。     

Treatment of malignant ovarian germ cell tumors: response to vincristine, dactinomycin, and cyclophosphamide (preliminary report)

From November 1971 to November 1975, 27 patients with malignant germ cell tumors of the ovary (excluding pure dysgerminoma and tumors containing trophoblastic elements) were treated with vincristine, dactinomycin, and cyclophosphamide; 12 patients received other therapy. Fourteen tumors were pure endodermal sinus tumors, two were embryonal carcinomas, 11 were mixed germ cell tumors and 12 were immature teratomas. Of 23 patients with surgically resected disease (Stages I-IIA) only seven have failed. Median follow-up for 16 patients remaining free of disease is 24.5 months. Restaging (second-look) laparotomies were done in 15 patients. Eight were negative. Fifteen of the patients had tumors with endodermal sinus elements. Six of these have failed. Of 16 patients with advanced disease (Stage IIB, III and recurrent), eight have responded to chemotherapy, eight have failed. Median follow-up period for those remaining free of disease is 26.5 months. Six have had negative second-look surgery and one had mature teratoma. Four of eight cases which contained endodermal sinus elements responded to chemotherapy and remain disease-free. Grade 3 hematologic toxicity was seen in eight patients, dose-limiting gastrointestinal toxicity in five patients, dose-limiting neurotoxicity in five patients.     

The significance of atypia within teratomatous metastases after chemotherapy for malignant germ cell tumors

The completely resected teratomatous metastases of 55 patients who had been treated with cisplatin-based combination chemotherapy for non-seminomatous germ cell tumors were reviewed to see if cellular atypia had an effect with respect to recurrent disease. The degree of atypia of the epithelial and mesenchymal elements was assessed on the basis of the cytologic features and mitotic activity. Twenty-three percent of the cases contained high-grade epithelial elements, whereas high-grade mesenchymal elements occurred in 18% of the cases; in addition there were nine cases classified as showing frankly malignant teratomatous elements. The presence of cytologically disturbing epithelial and mesenchymal elements (which, however, lacked an invasive malignant pattern) correlated with an increased incidence of recurrent teratoma compared to less atypical teratomatous elements (23% vs. 6% for epithelial elements, and 18% vs. 9% for mesenchymal elements, respectively). This difference, however, was not statistically significant (P greater than 0.05). There was no correlation between teratomatous atypia and recurrent, non-teratomatous germ cell tumor. The presence of an invasive malignant pattern did identify patients at significantly increased risk for recurrent teratoma-derived tumor. The authors conclude that cytologic atypia in the absence of invasion is not sufficient justification for altering the usual therapeutic strategies for patients with teratomatous metastases.     

Wait-and-see policy in clinical stage I non-seminomatous germ cell tumors of the testis

Thirty-three patients with a non-seminomatous germ cell tumor of the testis in clinical stage I were treated only by orchidectomy. The very careful follow-up--with tumor marker assays every 3 weeks, chest X-rays every 6 weeks and CT-scans of the lungs and retroperitoneum every 3 months--revealed metastases in 7 of the patients (21%). All these relapses were diagnosed within 6 months of the orchidectomy. Para-aortic node metastases were found in 5 of the 7 patients, with additional inguinal node metastases in 1 and additional lung metastases in 1; 2 patients had only lung metastases. Six of the 7 patients with a relapse were given chemotherapy (PVB); 1 patient refused chemotherapy. In view of residual disease a surgical excision was performed; it revealed necrosis as well as mature teratoma. All 33 patients are still alive, the post-orchidectomy follow-up period being 12-38 months.     

Survival and reproductive function after treatment of malignant germ cell ovarian tumors.

PURPOSE: Germ cell ovarian tumors are curable. The possible sequelae of chemotherapy on long-term survivors are still unknown, but these patients may expect normal lives. The aim of this study was to evaluate the outcome and reproductive function in a population of women treated since 1982. MATERIALS AND METHODS: Between 1982 and 1996, 169 women with malignant germ cell ovarian tumors were seen (70 dysgerminomas, 28 endodermal sinus tumors, 24 mixed tumors, and 47 immature teratomas). Seventy-one had advanced or recurrent disease. Fertility-sparing surgery was performed in 138 (81%) women, 81 of whom received postoperative chemotherapy. RESULTS: With a median follow-up of 67 months, the survival rate was 94% for dysgerminoma, 89% for endodermal sinus tumors, 100% for mixed types, and 98% for immature teratoma. For women who were treated conservatively, the survival rate was 98%, 90%, 100%, and 100%, respectively. Two women had adnexal recurrences, and both received salvage treatment. After treatment, all but one postpubertal woman had recovery of menses within 9 months. During follow-up, 12 untreated and 20 treated patients had 55 conceptions. We recorded 40 pregnancies at term, six terminations, and nine miscarriages. Four malformations were observed: one in 14 conceptions of patients who had not received chemotherapy and three in 41 conceptions of treated patients. CONCLUSION: Irrespective of subtype and stage, conservative surgery should become the standard approach to treating most patients with malignant ovarian germ cell tumors. Fertility seems to be only marginally affected by treatments. Miscarriages are in the expected range for the general population. The malformation rate is slightly higher than in the general population, but no significant difference was seen between patients who did and did not receive chemotherapy.