The Role of Surgery in the Management of Gestational Trophoblastic Neoplasia The Hungarian Experience.

OBJECTIVE: To review the role of surgery in the management of gestational trophoblastic neoplasia (GTN) over the past 38 years in our national trophoblastic disease center. STUDY DESIGN: Between January 1, 1977, and December 31, 2014, 371 patients with low-risk GTN and 190 patients with high-risk GTN were treated with chemotherapy, surgical interventions, or both. The indications for hysterectomy included excision of large uterine tumor masses, uterine hemorrhage or sepsis, or a drug-resistant uterine focus. Metastases were excised due to the presence of drug-resistant foci or complications of disease such as hemorrhage. RESULTS: Over the period of 1977-2014 74 hysterectomies, 15 resections of vaginal metastases, 3 omentectomies, 13 adnexectomies, 9 lung resections, I nephrectomy, 1 lung resection and nephrectomy, and 2 craniotomies were performed among our patients. While hysterectomy was performed in 51 (26.8%) of 190 high-risk patients, hysterectomy was performed in only 23 (6.2%) of 371 low-risk patients (p < 0.01). From 1977-2006 metastases were resected in 18.3% (26/142) and from 2007-2014 in 16.7% (8/48) of high-risk patients. CONCLUSION: In our center surgery, particularly in the form of hysterectomy, still plays a valuable role in the management of both low- and high-risk GTN.

Changes in the management of high-risk gestational trophoblastic neoplasia in the National Trophoblastic Disease Center of Hungary.

OBJECTIVE: To compare the clinical management of patients with high-risk gestational trophoblastic neoplasia (GTN) among the periods of 1977-1990, 1991-2000, and 2001-2012 at the National Trophoblastic Disease Center of Hungary and to assess the efficacy of the FIGO 2000 staging and risk factor scoring system in comparison to the original WHO prognostic scoring system (1983). STUDY DESIGN: We reviewed the medical records of 185 patients with high-risk GTN. From 1977-2000, patients were classified according to the original WHO prognostic scoring system (1983). From 2001-2012, high-risk patients were categorized by the FIGO 2000 system. We assessed the efficacy of MAC and EMA-CO primary combination chemotherapies. For 1977-2006 and 2007-2012 we assessed the efficacy of MAC and EMA-CO primary combination chemotherapies. RESULTS: From 1977-1990, 63 high-risk patients (average, 4-5 patients/year), from 1991-2000, 50 high-risk patients (average, 5 patients/year), and from 2001-2012, 72 high-risk patients (average, 6 patients/year) were treated primarily with combination chemotherapy (MAC and/or EMA-CO and/or CEB). From 1977-2006, 100 high-risk patients received MAC primary combination chemotherapy and 17 cases received EMA-CO. The ratio of primary MAC primarily with and EMA-CO therapy among our high-risk patients was 5.9 (100/17) over the referred period. From 2007-2012, 21 high-risk patients were treated with primary MAC chemotherapy and 16 patients received EMA-CO. The MAC/EMA-CO ratio over this time interval was 1.3 (21/16). CONCLUSION: We attained complete remission in 95.7% of the high-risk patients. During the last 6 years the use of EMA-CO primary combination chemotherapy increased among our high-risk patients, which has resulted in increased efficacy and fewer side effects.

Clinical epidemiology and management of gestational trophoblastic neoplasia in Hungary in the past 34 years.

OBJECTIVE: To review our clinical experience in the treatment of patients with gestational trophoblastic neoplasia (GTN) over the past 34 years in our national trophoblastic disease center. STUDY DESIGN: Between January 1, 1977, and December 31, 2010, 331 patients with low-risk GTN and 174 patients with high-risk GTN (altogether 505) were treated. The patients were directed to the national trophoblastic disease center from all parts of Hungary. The patients were between 14 and 54 years of age, with an average age of 28.7 years. Primary chemotherapy was selected based upon the patient's stage and prognostic score of GTN. RESULTS: Among 237 low-risk patients, 228 (96.2%) achieved remission as a result of primary methotrexate (MTX) therapy. Out of 94 low-risk patients 90 (95.7%) achieved remission as a result of primary actinomycin-D (Act-D) therapy. MTX, Act-D and cyclophosphamide (MAC) as a primary therapy was used in 118 high-risk cases, and 110 (93.2%) patients achieved complete remission. A total of 32 high-risk patients were treated with the etoposide, high-dose MTX/folinic acid, Act-D, cyclophosphamide and vincristine (EMA-CO) regimen, and of 26 primary therapies complete remission was achieved in 21 (80.8%) cases. Primary cisplatin, etoposide and bleomycin (CEB) therapy was successful in 16 of 17 high-risk cases (94.1%). Metastases were found in 47.3% (239/505) of the patients. Hysterectomy was performed in 68 of 505 (13.5%) cases. Chemotherapy, surgical intervention or other supplementary treatments resulted in 100% remission in cases of nonmetastatic and metastatic low-risk disease. Comparison of mean prognostic scores resulted in significant differences between CEB and MAC, CEB and EMA-CO, and MAC and EMA-CO. CONCLUSION: Our data indicate that MTX/folinic acid or Act-D should be the primary treatment in patients with nonmetastatic or metastatic low-risk GTN. Patients with high-risk metastatic GTN should be treated primarily with combination chemotherapy. Our data support the effectiveness of MAC, EMA-CO and CEB regimens. Results also show that patient care under the direction of experienced clinicians serves to optimize the opportunity for cure and minimize morbidity.

30 years' experience in the treatment of low-risk gestational trophoblastic neoplasia in Hungary.

OBJECTIVE: To review the clinical experience in the treatment of patients with low-risk gestational trophoblastic neoplasia (GTN) over the past 30 years in a national trophoblastic disease center. STUDY DESIGN: Between January 1, 1977, and December 31, 2007, 302 patients with low-risk GTN were treated. The patients were directed to our institution from all parts of Hungary. The patients were 14 to 53 years of age with an average age of 28.3 years. Methotrexate (MTX)/folinic acid or actinomycin-D (Act-D) primary chemotherapy was selected based upon the patient's stage and prognostic score of GTN. RESULTS: Among 218 low-risk patients, 210 (96.3%) achieved remission as a result of MTX therapy. In 8 patients (3.7%), MTX-Act-D-cyclophosphamide (MAC) combination chemotherapy was needed to achieve complete remission, in some cases assisted by operation. Among 84 patients, 81 (96.4%) achieved remission as a result of Act-D therapy. In 3 cases (3.6%) complete remission was achieved by MAC combination chemotherapy. We detected metastases in 22.8% (69/302) of our low-risk patients. Chemotherapy, surgical intervention or other supplementary treatments resulted in 100% remission in cases of low-risk nonmetastatic and metastatic disease. CONCLUSION: Our data indicate that MTX/folinic acid or Act-D should be the primary treatment in patients with nonmetastatic or metastatic low-risk GTN. Importantly, patients with resistance to single-agent chemotherapy regularly achieve complete remission with MAC combination chemotherapy. Results show that patient care under the direction of experienced clinicians serves to optimize the opportunity for cure and minimize morbidity.

Primary pulmonary choriocarcinoma: a case report.

BACKGROUND: Primary pulmonary choriocarcinoma (PPC) is an extremely rare clinical entity. In contrast with gestational trophoblastic tumors that show an extreme sensitivity for chemotherapy, extragonadal choriocarcinomas are mostly unresponsive to surgical and chemotherapeutic treatment and are associated with poor prognosis. The reason non-gestational choriocarcinomas behave so differently from gestational tumors is unknown. CASE: In the present case we report a 30-year-old female patient with primary choriocarcinoma of lung localization who was successfully treated with surgical resection and multiple cycles of combination chemotherapy. During her recovery she was followed up by human chorionic gonadotropin (hCG) titer measurement, and after 1 year of close surveillance of beta-hCG levels her disease achieved complete remission. CONCLUSION: Because of the extreme rarity of this malignancy, there are no standardized therapeutic guidelines for treatment. The first choice in treatment of PPC is surgical resection. Postoperatively chemotherapy is indicated immediately, because definitive histologic diagnosis is not essential before chemotherapy since beta-hCG is a reliable tumor marker for choriocarcinoma.

25 years' experience in the treatment of gestational trophoblastic neoplasia in Hungary.

OBJECTIVE: To review our clinical experience in the treatment of gestational trophoblastic neoplasia (GTN) over the past 25 years in our national trophoblastic disease center. STUDY DESIGN: Between January 1, 1977, and December 31, 2001, we treated 355 patients with GTN. The patients were between 14 and 53 years of age, with an average of 28.3. Primary chemotherapy was selected based on the patient's stage of gestational trophoblastic tumor (GTT) and prognostic score. RESULTS: We found metastases in 49.3% (175 of 355) of our patients. Of 173 patients, 162 (93.2%) achieved remission as a result of methotrexate therapy. In 11 patients (6.8%) complete remission was achieved by combination chemotherapy, in some cases assisted by operation. Of 68 patients, 63 (92.6%) achieved remission as a result of actinomycin D therapy, and 5 (7.4%) achieved complete remission by combination chemotherapy. Chemotherapy, surgical intervention or other supplementary treatments resulted in 100% successful therapy in cases of nonmetastatic and low-risk metastatic disease. CONCLUSION: According to our experience, methotrexate/folinic acid or actinomycin D should be the primary treatment in patients with nonmetastatic or low-risk metastatic GTN. Patients with resistance to single-agent chemotherapy regularly achieve remission with combination chemotherapy.

Alloimmune and autoimmune background in recurrent pregnancy loss - successful immunotherapy by intravenous immunoglobulin.

PROBLEM: Immunotherapies [leukocyte immunization, intravenous immunoglobulin (IVIG)] introduced to treat women with recurrent spontaneous abortions (RSA) have still controversial results in most clinical trials. A selection of these patients would be advantageous for higher efficacy. METHOD OF STUDY: A complex immunological panel assay was offered to patients with reproductive failure without any other known cause. We focused here on the cellular immunological parameters. RESULTS: High cytotoxic T lymphocyte precursor frequency and cell-mediated cytotoxic activity and a rather high natural killer cell activity were found in alloimmune RSA patients. Thirty-two patients were investigated by immunological assays and in 78% of the women an alloimmune background could be defined. The efficacy of IVIG treatment was 96% in this group. CONCLUSIONS: The novel cellular immunological assays proved to be favourable for the indication of RSA patients and showed the usefulness of this selection process for effective immunotherapy.

How long should patients be followed after molar pregnancy? Analysis of serum hCG follow-up data.

OBJECTIVE: We analyzed human chorionic gonadotropin (hCG) follow-up data of patients with molar pregnancy. Women often do not complete recommended post-disease screening. Our purpose was to determine if continuing follow up of uncomplicated molar cases beyond attaining undetectable hCG levels is necessary for detecting relapse of gestational trophoblastic disease. STUDY DESIGN: One hundred fifty patients treated at Hungarian National Health Center were analyzed. Those who developed persistent disease before hCG had become undetectable were excluded from further analysis (n=24; 16%). RESULTS: Among 126 uncomplicated cases, 72 patients (57%) completed follow up, and 54 (43%) discontinued their protocol before it had been completed. Of 120 patients who achieved at least one undetectable hCG level, none had any evidence of relapse. CONCLUSION: In uncomplicated hydatidiform mole, our analysis indicates that once undetectable serum hCG levels are attained, relapse is unlikely. Although further monthly checks are advisable, the likelihood of recurrence appears very low.