Stage IV Gestational Choriocarcinoma Diagnosed in the Third Trimester.

BACKGROUND: Gestational trophoblastic neoplasia rarely occurs in term pregnancies. Stage IV choriocarcinoma treated with conventional chemotherapy can result in death as a result of hemorrhagic sequelae at tumor sites. CASE: A 30-year-old woman at 34 weeks of gestation presented with a persistent cough, worsening dyspnea, and vaginal bleeding. Chest radiograph demonstrated innumerable lung nodules, and quantitative ß-hcg concentration exceeded 1.3 million milli-international units/mL. Cesarean delivery was performed for presumed abruption. Placental pathology demonstrated choriocarcinoma, and imaging confirmed stage IV disease with a World Health Organization score of 14. Remission was achieved after two courses of low-dose induction chemotherapy followed by 10 cycles of combination chemotherapy. CONCLUSION: Gestational trophoblastic neoplasia should be considered in a pregnant or postpartum woman presenting with atypical vaginal bleeding. Coexistent pulmonary or neurologic findings may suggest advanced disease.

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.

Mortality rate of gestational trophoblastic neoplasia with a FIGO score of ≥13.

BACKGROUND: Gestational trophoblastic diseases include premalignant (partial and complete hydatidiform moles) and malignant entities referred to as gestational trophoblastic neoplasia. Use of the International Federation of Gynecology and Obstetrics prognostic score is encouraged in cases of gestational trophoblastic neoplasia to predict the potential for the development of resistance to single-agent chemotherapy. An International Federation of Gynecology and Obstetrics score of ≥7 defines a high-risk patient and requires combination chemotherapy. Appropriate and rapid diagnosis, treatment by specialized centers, and reduction of early deaths at the time of chemotherapy initiation have led to significant improvements in survival for patients with high-risk gestational trophoblastic neoplasia. There is a crucial need for the early identification of high-risk patients with gestational trophoblastic neoplasia who have an increased death risk to organize their treatment in highly specialized centers. OBJECTIVES: The purpose of this study was to describe cases of gestational trophoblastic neoplasia that have resulted in death, particularly in a subgroup with an International Federation of Gynecology and Obstetrics prognostic score of ≥13, for whom low-dose etoposide and cisplatin induction chemotherapy recently was shown to reduce early death rate. STUDY DESIGN: We identified 974 patients from the French Center for Trophoblastic Diseases who had a diagnosis of gestational trophoblastic neoplasia from November 1999 to March 2014. Among 140 patients who were at high risk of resistance to single-agent chemotherapy (International Federation of Gynecology and Obstetrics score, ≥7), 29 patients (21%) had a score of ≥13. Mortality rate was estimated with the use of the Kaplan-Meier method. RESULTS: The 5-year overall mortality rate, after the exclusion of placental site trophoblastic tumors and epithelioid trophoblastic tumors, was 2% for patients with gestational trophoblastic neoplasia (95% confidence interval, 1.25-3.13%). High-risk patients had a 5-year mortality rate of 12% (95% confidence interval, 7.49-18.9%). Patients with an International Federation of Gynecology and Obstetrics score of ≥13 had a higher 5-year mortality rate (38.4%; 95% confidence interval, 23.4-58.6%) and accounted for 52% of the deaths in the entire cohort. Early deaths, defined as those that occur within 4 weeks after treatment initiation, occurred in 8 patients of the entire cohort. Six of them had an International Federation of Gynecology and Obstetrics score of ≥13 at presentation, of whom 5 patients had brain and/or liver metastases. CONCLUSION: Gestational trophoblastic diseases with an International Federation of Gynecology and Obstetrics score of ≥13 have an increased risk of early death. We suggest that an International Federation of Gynecology and Obstetrics score of ≥13 becomes a consensual criterion for prediction of patients with gestational trophoblastic neoplasia with increased risk of death, particularly early death. These patients justify treatment in highly specialized gestational trophoblastic disease centers and may benefit from the use of induction low-dose etoposide and cisplatin.

Gestational trophoblastic neoplasia: treatment outcomes from a single institutional experience.

PURPOSE: To report the outcomes of gestational trophoblastic neoplasia (GTN) at a single institution and to determine the factors affecting response to chemotherapy and survival. METHODS/PATIENTS: From 1979-2010, we retrospectively reviewed the data of 221 patients treated at our center. GTN Patients were assigned to low-risk (score ≤6) or high-risk (score ≥7) based on the WHO risk factor scoring system. Overall survival (OS) probabilities were estimated using Kaplan-Meier method. Logistic regression was applied to study the impact of different factors on the response to initial therapy. RESULTS: Patients' OS rate was 97 %. Median age at diagnosis was 37 year. 131 (59 %) patients had low-risk and 88 (40 %) cases had high-risk GTN. Complete remission rates to initial chemotherapy in low-risk group were 53 % and 87 % for single-agent methotrexate or dactinomycin, respectively. In high-risk group, 94 % achieved complete remission to initial chemotherapy with etoposide, methotrexate, dactinomycin, cyclophosphamide, and vincristine (EMA-CO). Etoposide, cisplatin, and dactinomycin as primary therapy in high-risk patients was successful in 70 %, while bleomycin, etoposide, and cisplatin (BEP) was successful in 53 % of cases. Salvage chemotherapy, surgical intervention or radiation therapy resulted in overall complete remission of 90 % in low-risk and 73 % in high-risk groups. Factors associated with resistance to initial chemotherapy were advanced-stage III/IV (p = 0.005), metastatic site other than lung or vagina (p = 0.005) and high-risk prognostic score (p = 0.05). OS was significantly influenced by the type of antecedent pregnancy (molar 98 % vs. others 93 %; p = 0.04), FIGO stage (I, II 100 % vs. III, IV 94 %; p = 0.02), score (low-risk 100 % vs. high-risk 92 %; p = 0.01), and site of metastasis (lung/vagina 98 % vs. others 85 %; p = 0.002). CONCLUSIONS: GTNs have excellent prognosis if properly treated at experienced centers. Single-agent dactinomycin seems more effective for low-risk GTN. EMA-CO remains the preferred primary treatment regimen for high-risk group. The excellent outcome reflects the success of salvage therapy.

Brain metastases from gestational trophoblastic neoplasia: review of pertinent literature.

Brain metastasis from gestational trophoblastic neoplasia (GTN) is rare with about 222 cases documented in the literature and an incidence of about 11% in living GTN patients. Brain metastasis from GTN was part of a disseminated disease in 90% of patients, single metastases in the brain - 80% and located in the cerebrum - 90%. Brain metastasis was the only manifestation of metastatic GTN in 11.3% of patients, appeared synchronously with metastatic GTN in other sites of the body - 30.6% and was diagnosed from 0.3 to 60 months after diagnosis of metastatic GTN in other sites (most often in the lung) - 58.1%. Overall, 83.9% of patients with brain metastases from GTN had also lung metastases from GTN. Brain metastases from GTN showed a greater tendency to be hemorrhagic compared to brain metastases from other primaries. In patients with brain metastases from GTN, the best outcome was achieved with multimodal therapy including craniotomy, whole brain radiotherapy, and EP-EMA or EMA-CO chemotherapy. Nonetheless, brain metastasis from GTN is a grave disease with a median survival time from diagnosis of brain metastasis of about 12 months.

Gestational trophoblastic disease in the western region of Saudi Arabia (single-institute experience).

OBJECTIVE: To estimate the prevalence of gestational trophoblastic disease (GTD) in the western region of Saudi Arabia, and to evaluate the success of treatment and the effect of age and risk group on survival. METHODS: Between January 2001 and December 2010, all patients treated for GTD were identified from the King Abdulaziz University Hospital database. Patients with persistent disease were evaluated according to their clinical treatment outcomes. RESULTS: In total, 122 cases of GTD were identified in the database. Of these, 77 (63%) cases were diagnosed and received initial treatment at the study centre, resulting in an incidence of 1.26 cases per 1000 deliveries. The mean (±standard deviation) age of the study participants was 31.52 ± 10.8 years, mean gestational age at diagnosis was 12.42 ± 3.2 weeks, and mean follow-up for each patient was 24 months. There were 20 cases (26%) of persistent GTD after treatment. The majority of patients with low-risk disease were treated with single-agent methotrexate, with an overall success rate of 83%. The overall 5-year survival rate for all patients was 98%. Using the Wilcoxon (Gehan) test, risk group and age (cut-off 40 years) were not found to be significantly associated with survival (p=0.69). CONCLUSIONS: This single-institute study reports the first survival data for GTD for Saudi Arabia. However, the overall incidence of GTD in Saudi Arabia will be defined by establishment of a GTD registry.

Brain metastasis in gestational trophoblastic neoplasia: an update.

OBJECTIVE: To update the treatment of brain metastases in gestational trophoblastic neoplasia (GTN) at the Brewer Trophoblastic Disease Center, comparing treatment and outcomes from 1995-2009 with those from 1962-1994. STUDY DESIGN: Thirty-seven patients with GTN who had brain metastases at presentation (25, 68%) or who developed brain metastases during treatment (12, 32%) were treated with chemotherapy and brain irradiation at the Brewer Center between 1962 and 2009 (26 prior to 1995 and 11 since 1995). Patients underwent whole brain irradiation (2400-4000 cGy in 200-300 cGy fractions prior to 1995, and 2400-3000 cGy in 200 cGy fractions since 1995) +/- radiosurgery. RESULTS: Of 11 patients with GTN treated for brain metastases since 1995, 7 (64%) are alive, and 4 died. Six (55%) of the 11 patients treated after 1995 were diagnosed with brain metastases during treatment, 3 (50%) of whom were cured, compared to 6 (23%) of the 26 patients treated before 1995, only 1 (17%) of whom was cured. CONCLUSION: The overall survival for all 37 patients with GTN who had brain metastases from 1962-2009 was 51% (19/37): 46% (12/26) before 1995 and 64% (7/11) after 1995. Survival was significantly influenced by symptoms at presentation: 100% (8/8) for asymptomatic patients versus 41% (7/17) for symptomatic patients (p=0.0005). No patient who died had uncontrolled brain metastases. In our experience, therefore, brain metastases in GTN are curable with a combination of systemic multiagent chemotherapy and whole brain irradiation.

Treatment of gestational trophoblastic disease--a 10-year experience.

A retrospective descriptive study about the presence of metastases, epidemiological characteristics and treatment of 104 patients suffering from gestational trophoblastic disease was performed in the period from 1st Jan, 2000 to 31st December, 2010. Of eleven patients who were found to have metastases (10.6%), 72.7% had pulmonary metastases, 27.3 had vaginal, and one patient had both pulmonary and brain metastases. The average age was 33.9. Antecedent molar pregnancy was recorded in 63.6% patients. Invasive mole was more frequent than choriocarcinoma (63.6%). According to the World Health Organization criteria, 7 patients (63.6%) had high risk score (the average World Health Organization score was 8.4). All patients were treated by chemotherapy, the average number of courses being 1.8. Complete remission was achieved in all patients. Treatment of metastatic disease depends on multiple factors. However, combined chemotherapy is the universally accepted treatment. If chemotherapy is individualized and applied on time, the prognosis is good, even in cases with cerebral metastases.

Management of metastatic high-risk gestational trophoblastic neoplasia: FIGO stages II-IV: risk factor score > or = 7.

OBJECTIVE: To evaluate treatment of metastatic high-risk gestational trophoblastic neoplasia (GTN), including durable complete response rates to chemotherapy, factors affecting response to therapy, and overall survival. STUDY DESIGN: Forty women with metastatic high-risk GTN (International Federation of Gynecology and Obstetrics [FIGO] stages II-IV, score > or = 7) completed treatment between 1986 (when EMA-CO became the standard chemotherapy for high-risk disease) and 2009, including 26 who were treated primarily and 14 who were treated secondarily. Patients who had incomplete responses or developed resistance to EMA-CO or other methotrexate-containing regimens were treated with drug combinations employing etoposide and a platinum agent with or without bleomycin or ifosfamide. Adjuvant radiotherapy and surgery were used in selected patients. Clinical response and survival as well as factors affecting outcomes were analyzed retrospectively. RESULTS: The overall survival rate was 90% (36 of 40): 92% (24/26) for primary treatment and 86% (12/14) for secondary treatment. Twenty-one patients (53%) had durable complete clinical responses to initial treatment, 15 patients (37%) developed resistance to initial chemotherapy but were subsequently placed into lasting remission with platinum-based chemotherapy with or without surgery and 4 patients (10%) died of widespread metastatic disease. Durable complete clinical response to initial chemotherapy was significantly influenced by FIGO stage (II and III, 63%, vs. IV, 31%, p = 0.05) and risk factor score (< 12, 71%, vs. > or = 12, 32%, p < 0.02). Survival was also significantly associated with both FIGO stage (II and III, 100%, vs. IV, 69%, p < 0.01) and score (< 12, 100%, vs. > or = 12, 79%, p < 0.05). CONCLUSION: The use of EMA-CO chemotherapy as primary treatment and platinum-based chemotherapy along with surgical excision of resistant disease as secondary treatment for patients with metastatic high-risk GTN resulted in a survival rate of 90%. All patients who died had FIGO stage IV and risk factors scores > or = 12.

Vaginal metastases complicating gestational trophoblastic neoplasia.

OBJECTIVE: To evaluate the clinical experience and outcomes of patients with gestational trophoblastic neoplasia (GTN) complicated by vaginal metastases. STUDY DESIGN: A retrospective descriptive study of patients with vaginal metastases from GTN treated at the University of the Philippines-Philippine General Hospital (UP-PGH) Trophoblastic Disease Section from 1998 to 2008. RESULTS: Vaginal metastases were present in 46 (11%) of the 424 patients treated for GTN. The majority of the patients (69.6%) were stage III, 19.6% were stage II and 10.9% were stage IV. Thirty-six patients (78.3%) were high-risk patients with World Health Organization scores of > 7. Eleven patients (24%) had bleeding vaginal lesions on initial consultation, and transfusion of packed red blood cells was necessary in all of these patients. Interventions to control bleeding included vaginal packing with methotrexate solution (5/11 or 46%), ligation of bleeders with bilateral internal iliac artery ligation (4/11 or 36%), over sewing of bleeding vaginal lesions (2/11 or 18%), ligation of vaginal bleeders (3/11 or 27%), vaginal packing only (6/11 or 54%), methotrexate infiltration of vaginal mass (1/11 or 9%) and external beam radiation (1/11 or 9%). Of the 37 patients who were given chemotherapy, 26 (70%) had complete remission. CONCLUSION: Prognosis with vaginal metastasis mainly depends on disease extent. Favorable response to chemotherapy was observed in low-risk patients with pretreatment hCG of < 100,000 mIU/mL and metastases confined to the vagina and/or pelvic area only.

Metastasis of gestational trophoblastic neoplasia to the spinal canal: a case report.

BACKGROUND: Spinal canal metastasis secondary to gestational trophoblastic neoplasia (GTN) is a rare condition. CASE: A 21-year-old female presented with symptoms of cauda equina compression by an extradural metastasis from GTN. The patient received multiagent chemotherapy combined with intrathecal methotrexate administration. Her neurologic symptoms improved remarkably after the cessation of chemotherapy. During the 21-month follow-up period, she was asymptomatic and has shown overall improvement in well-being. CONCLUSION: Spinal canal metastasis of GTN is a possibility that must be considered in young women with a history of hydatidiform mole who have neurologic symptoms or signs, which were improved completely by chemotherapy alone in this case.

Gestational trophoblastic tumor with liver metastasis after misoprostol abortion.

BACKGROUND: Early elective medical abortion is performed frequently in different countries of the world. Serious complications like gestational trophoblastic neoplasia (GTN) are uncommon and mostly nonmetastatic. High risk metastatic GTN following medical abortion is a rare event which may occur coincidentally. CASE: A 26 year-old-woman, gravida 2 para 1, 6 weeks after misoprostol abortion presented with sever nausea, vomiting, and right upper abdominal pain. Human chorionic gonadotropin (hCG) level was 2,500,000 mIU/ml and metastatic work up revealed multiple liver metastases. She totally received nine cycles of EMA-CO (ethoposide- methotrexate- actinomycin- cyclophosphamide, vincristine) regimen for treatment and consolidation. Six months after treatment she is in complete remission. CONCLUSION: Follow up of patients after medical abortion by means of single serum hCG measurement is highly recommended for early diagnosis of complications including gestational trophoblastic tumor. EMA-CO regimen seems to be an effective and safe treatment for liver metastatic gestational trophoblastic neoplasia.

Patients with presenting unusual manifestations with gestational trophoblastic neoplasm: case series and review of literatures.

Early recognition of gestational trophoblastic neoplasms (GTN) will maximize the chances of cure with chemotherapy but some patients present with many different symptoms months or even years after the causative pregnancy making diagnosis difficult. Clinicians should be aware of the possibility of GTN in any reproductive age woman with bizarre central nervous system symptoms, gastrointestinal symptoms or radiographic evidence of metastatic tumor of unknown primary origin. We reported two cases of metastatic gestational trophoblastic neoplasms with bizarre pulmonary symptoms, one patient with small bowel metastasis, and two patients with brain metastasis presenting with unusual manifestations.

Usefulness of low-dose CT in the detection of pulmonary metastasis of gestational trophoblastic tumours.

AIM: To determine whether a low-dose spiral chest computed tomography (CT) examination could replace standard-dose chest CT in detecting pulmonary metastases in patients with gestational trophoblastic tumour (GTT). MATERIALS AND METHODS: In a prospective investigation, 67 chest CT examinations of 39 GTT patients were undertaken. All the patients underwent CT examinations using standard-dose (150 mAs, pitch 1, standard reconstruction algorithm) and low-dose (40 mAs, pitch 2, bone reconstruction algorithm) protocols. Two radiologists interpreted images independently. A metastasis was defined as a nodule within lung parenchyma that could not be attributed to a pulmonary vessel. The number of metastases detected with each protocol was recorded. The size of each lesion was measured and categorized as <5, 5-9.9, and > or = 10 mm. Wilcoxon's signed rank test was used to assess the difference between the numbers of lesion detected by the two protocols. RESULTS: The CT dose index (CTDI) for the standard-dose and low-dose CT protocols was 10.4 mGy and 1.4 mGy, respectively. One thousand, six hundred, and eighty-two metastases were detected by standard-dose CT, and 1460 lesions by the low-dose protocol. The numbers detected by low-dose CT were significantly less than those detected by standard-dose CT (Z=-3.776, p<0.001), especially for nodules smaller than 5mm (Z=-4.167, p<0.001). However, the disease staging and risk score of the patients were not affected by use of the low-dose protocol. CONCLUSION: Low-dose chest CT can be used as a staging and follow-up procedure for patients with GTT.

Treatment of metastatic gestational trophoblastic neoplasia.

Treatment of persistent gestational trophoblastic neoplasia (GTN) has been one of the success stories of modern day chemotherapy; however, occasional patients with metastatic disease still die. A potential difficulty in assessing published studies is that patient groups can be selected for treatment differently according to how risk categories are defined. The involvement of a specialist team from the outset is essential. Patients with low-risk metastatic GTN are treated successfully with single-agent chemotherapy using methotrexate or dactinomycin. Patients with high-risk metastatic disease receive combination chemotherapy regimens from the start. Worldwide experience has been accrued by use of regimens devised and tested by large centres. The high response rate and good long-term survival, as well as the tolerable acute and cumulative toxic effects, associated with use of etoposide, methotrexate and dactinomycin, alternating with cyclophosphamide and vincristine, make this protocol, or one of its variants, the current initial treatment of choice for patients. In view of the success of these regimens difficulty would be encountered in mounting a worthwhile randomised controlled trial; however, further well-designed studies are needed of novel approaches in very-high-risk and multiresistant disease.