ABSTRACT
OBJECTIVE: Presence of lung metastases in low-risk gestational trophoblastic neoplasia (GTN) is generally considered not to influence prognosis. However, in a recent study in the Netherlands, GTN patients with lung metastases had a higher recurrence rate and more disease-specific deaths compared with patients without metastases. The aim of the present study was to validate these findings in a different country. DESIGN: Historical cohort study. SETTING: Charing Cross Hospital, United Kingdom. POPULATION: A total of 1040 low-risk GTN patients treated with methotrexate (MTX) between 2002 and 2016 were identified: 65 with lung metastases (group 1) and 975 without metastases (group 2). METHODS: Baseline characteristics, MTX resistance, survival and recurrence rates were recorded and compared between both groups. MAIN OUTCOME MEASURES: MTX resistance, recurrence rate and survival. RESULTS: The occurrence of MTX resistance and median number of MTX courses to achieve remission was significantly higher in patients with lung metastases than patients without metastases (60% versus 38.9%, P = 0.001; and nine versus six courses, P < 0.001). All choriocarcinoma patients (n = 4) with lung metastases developed MTX resistance. The recurrence rate was also higher in group I (9.2% versus 2.7%; P = 0.012). Disease-specific survival was 100% in both groups. CONCLUSIONS: The presence of lung metastases at the start of MTX therapy is associated with increased incidence of MTX resistance and recurrence in low-risk GTN without affecting overall survival, which remains 100%. However, individuals with low-risk choriocarcinoma with lung metastases are likely to become resistant to MTX and primary multi-agent chemotherapy should be considered. TWEETABLE ABSTRACT: The presence of lung metastases appears to increase the risk of recurrence in low-risk GTN, but does not affect overall cure rates and survival.
Subject(s)
Choriocarcinoma , Drug Resistance, Neoplasm/drug effects , Gestational Trophoblastic Disease , Lung Neoplasms , Methotrexate , Adult , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/adverse effects , Choriocarcinoma/drug therapy , Choriocarcinoma/pathology , Cohort Studies , Female , Gestational Trophoblastic Disease/drug therapy , Gestational Trophoblastic Disease/pathology , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/mortality , Lung Neoplasms/secondary , Methotrexate/administration & dosage , Methotrexate/adverse effects , Middle Aged , Neoplasm Staging , Netherlands/epidemiology , Outcome Assessment, Health Care , Pregnancy , Recurrence , Risk Assessment/methods , Risk Assessment/statistics & numerical data , United Kingdom/epidemiologyABSTRACT
OBJECTIVE: Epithelioid Trophoblastic Tumor (ETT) is an extremely rare form of Gestational Trophoblastic Neoplasia (GTN). Knowledge on prognostic factors and optimal management is limited. We identified prognostic factors, optimal treatment, and outcome from the world's largest case series of patients with ETT. METHODS: Patients were selected from the international Placental Site Trophoblastic Tumor (PSTT) and ETT database. Fifty-four patients diagnosed with ETT or mixed PSTT/ETT between 2001 and 2016 were included. Cox regression analysis was used to identify prognostic factors for overall survival (OS). RESULTS: Forty-five patients with ETT and 9 patients with PSTT/ETT were included. Thirty-six patients had FIGO stage I and 18 had stages II-IV disease. Patients were treated with surgery (nâ¯=â¯23), chemotherapy (nâ¯=â¯6), or a combination of surgery and chemotherapy (nâ¯=â¯25). In total, 39 patients survived, including 22 patients with complete sustained hCG remission for at least 1â¯year. Patients treated with surgery as first line treatment had early-stage disease and all survived. Most patients treated with chemotherapy with or without surgery had FIGO stages II-IV disease (55%). They underwent multiple lines of chemotherapy. Eleven of them did not survive. Interval since antecedent pregnancy and FIGO stage were prognostic factors of OS (pâ¯=â¯0.012; pâ¯=â¯0.023 respectively). CONCLUSIONS: Advanced-stage disease and an interval of ≥48â¯months since the antecedent pregnancy are poor prognostic factors of ETT. Surgery seems adequate for early-stage disease with a shorter interval. Advanced-stage disease requires a combination of treatment modalities. Because of its rarity, ETT should be treated in a centre with experience in GTN.
Subject(s)
Trophoblastic Neoplasms/diagnosis , Trophoblastic Neoplasms/therapy , Adult , Databases, Factual , Epithelioid Cells/pathology , Female , Humans , Neoplasm Staging , Prognosis , Trophoblastic Neoplasms/pathologyABSTRACT
INTRODUCTION: The surgical management of girls with masculinized genitalia is gradually changing towards a more conservative approach. Reports on loss of clitoral sensitivity and related impairment of sexual function in women after feminizing genital surgery in childhood have been pivotal in this evolution. An exposed clitoral glans is occasionally seen at follow-up, and while patients may complain of aesthetics, no clitoral discomfort secondary to glans exposure has been reported. A technique has been developed to reconstruct the clitoral hood and the present study reports the preliminary results. OBJECTIVES: To report the novel technique and preliminary results of clitoral hood reconstruction to cover an exposed glans after previous clitoroplasty in patients with congenital adrenal hyperplasia (CAH). PATIENTS AND METHODS: Six female patients (mean age 13, range 4-21 years) with CAH sought medical help for clitoral concerns after previous reduction clitoroplasty. In two of the six patients, the main complaint was clitoral hypersensitivity or even pain. The clitoral glans was completely exposed in all patients, who were subsequently treated with a bi-laminar V-Y clitoral hoodplasty to create a mobile and natural-looking clitoral hood composed of an inner and outer preputial skin layer. RESULTS: Postoperative covering of the glans was complete in five patients, and partial in one. The two patients with pre-operative pain became asymptomatic; all six patients were pleased with the cosmetic postoperative results. CONCLUSION: Clitoral hoodplasty provides simple, yet effective, relief for women with cosmetic concerns or clitoral discomfort after previous feminizing surgery.
Subject(s)
Adrenal Hyperplasia, Congenital/complications , Clitoris/surgery , Disorders of Sex Development/surgery , Genitalia, Female/abnormalities , Plastic Surgery Procedures/methods , Adolescent , Adrenal Hyperplasia, Congenital/diagnosis , Child , Child, Preschool , Cohort Studies , Disorders of Sex Development/etiology , Disorders of Sex Development/physiopathology , Female , Follow-Up Studies , Genitalia, Female/surgery , Humans , Patient Satisfaction , Retrospective Studies , Risk Assessment , Suture Techniques , Treatment Outcome , Urogenital Surgical Procedures/methods , Wound Healing/physiology , Young AdultABSTRACT
BACKGROUND: Gestational trophoblastic disease (GTD) represents a heterogeneous group of disorders. Wide variations in incidence rates are reported worldwide, probably explained by a lack of centralized databases and heterogeneity in case definition. The aim of the present study was to determine the trends in incidence of GTD in the last 20 years with the use of population-based data. PATIENTS AND METHODS: Data on patients with pathologically confirmed diagnosis of GTD between 1994 and 2013 were obtained from PALGA, a nationwide archive containing all pathology reports in the Netherlands. RESULTS: In the 20-year period 6343 cases were registered with GTD, representing an overall incidence rate of 1.67 per 1000 deliveries per year. An initial rise in incidence rate was seen over the first 10 years (0.075 per year, 95% CI 0.040-0.109), followed by a stabilization from 2004 to 2013 (increase per year 0.011, 95% CI -0.017-0.040). Although partial hydatidiform mole (HM) was more common in earlier years, complete and partial HM reached comparable incidence rates of 0.68 and 0.64 per 1000 deliveries respectively from 2009 onwards. In the last decade, unspecified HM diagnosis declined significantly from 0.14 per 1000 deliveries in 2003 to 0.03 per 1000 deliveries (per year -0.011, CI -0.016-0.06), suggesting improved diagnostic analyses. CONCLUSION: After an initial rise in GTD incidence in the Netherlands rates remained steady from 2004 onwards. As pathological confirmation is currently the norm and advanced pathological techniques are now widely available, true steady incidence rates may have been reached.
Subject(s)
Gestational Trophoblastic Disease/epidemiology , Adolescent , Adult , Databases, Factual , Female , Gestational Trophoblastic Disease/pathology , Humans , Hydatidiform Mole/epidemiology , Hydatidiform Mole/pathology , Incidence , Netherlands/epidemiology , Population Surveillance , Pregnancy , Registries , Young AdultABSTRACT
OBJECTIVE: To describe fatal cases of gestational trophoblastic neoplasia (GTN) over four decades and evaluate whether treatment was given according to the protocol and reveal possible implications for future management. DESIGN: Retrospective cohort study. SETTING: The Netherlands. POPULATION: Women who died from GTN from 1971 to 2011. METHODS: Records from the Dutch Central Registry for Hydatidiform Moles and the Working Party on Trophoblastic Disease were used to identify fatal cases of GTN. MAIN OUTCOME MEASURES: Disease extent, risk classification, treatment regimens and cause of death. RESULTS: Twenty-six women died from GTN. In five cases GTN developed after a hydatidiform mole and in 19 cases following term pregnancy. Half of the women died between 1971 and 1980, when women were not yet classified as having low-risk or high-risk disease and were therefore not yet treated accordingly. A major decline in the number of deaths was seen after the first decade, with a further decrease from 1981 to 2011. Early death occurred in nine women. In four of these women, death was treatment-related. Women who died more than 4 weeks after the start of treatment mostly died from metastatic tumour (n = 14). CONCLUSIONS: The yearly number of women who died from GTN decreased considerably over the last four decades. Appropriate risk classification is essential to start optimal initial therapy and to prevent therapy resistance. Women with post-term choriocarcinoma represented a large proportion of the dead women and we propose that these women are considered as having high-risk disease.
Subject(s)
Gestational Trophoblastic Disease/mortality , Guideline Adherence , Adult , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cause of Death , Choriocarcinoma/mortality , Choriocarcinoma/pathology , Choriocarcinoma/therapy , Cohort Studies , Combined Modality Therapy , Cyclophosphamide/therapeutic use , Dactinomycin/therapeutic use , Etoposide/therapeutic use , Female , Gestational Trophoblastic Disease/pathology , Gestational Trophoblastic Disease/therapy , Humans , Hydatidiform Mole/mortality , Hydatidiform Mole/pathology , Hydatidiform Mole/therapy , Hysterectomy , Methotrexate/therapeutic use , Middle Aged , Neoplasm Metastasis , Netherlands/epidemiology , Practice Guidelines as Topic , Pregnancy , Retrospective Studies , Risk Assessment , Treatment Outcome , Uterine Neoplasms/mortality , Uterine Neoplasms/pathology , Uterine Neoplasms/therapy , Vincristine/therapeutic useABSTRACT
Hydatidiform mole is the most frequently-occurring gestational trophoblastic disease (GTD). Patients with GTD have elevated human chorionic gonadotrophin (HCG) produced by the trophoblast. After evacuation of the mole, weekly serum HCG determinations can be used to assess whether the trophoblast is persisting or regressing based on the standardised normal Nijmegen serum HCG regression curve. The serum HCG pattern is used to establish the diagnosis 'persistent trophoblastic disease'. Treatment with monochemotherapy in the form of methotrexate is the treatment of choice. For about 80% of women with a persistent trophoblastic disease following a molar pregnancy this treatment will lead to a complete remission of the disorder. If resistance to methotrexate occurs then a combined therapy is indicated. A recently developed, and as yet unvalidated, normogram for the serum HCG level during methotrexate treatment might in the near future be able to identify patients with methotrexate resistance at an early stage. Hysterectomy or curettage may be indicated as part of therapy in selected patients. The incidence of choriocarcinoma after a live birth is estimated at 1 in every 40,000 full-term pregnancies. These patients have a high risk for resistance to methotrexate (75%). Treatment of these patients with primary combination therapy at a specialised medical centre is then indicated.
Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Chorionic Gonadotropin/blood , Gestational Trophoblastic Disease/blood , Hydatidiform Mole/blood , Methotrexate/therapeutic use , Adult , Choriocarcinoma/blood , Choriocarcinoma/epidemiology , Drug Resistance , Female , Gestational Trophoblastic Disease/diagnosis , Gestational Trophoblastic Disease/therapy , Humans , Hydatidiform Mole/diagnosis , Hydatidiform Mole/therapy , Hysterectomy , PregnancyABSTRACT
Routine screening for maternal immunization in a 36-year-old woman revealed an alloimmunization against the high-incidence Vel antigen during a second pregnancy. Because of the development of immunoglobulin G-type anti-Vel, the infant developed haemolytic disease of the newborn, with severe jaundice and reticulocytosis. Phototherapy was needed to reduce hyperbilirubinaemia.
Subject(s)
Erythroblastosis, Fetal/etiology , Isoantibodies/immunology , Adult , Blood Group Antigens/immunology , Erythroblastosis, Fetal/immunology , Female , Humans , Hyperbilirubinemia/therapy , Immunoglobulin G , Infant, Newborn , Phototherapy , PregnancyABSTRACT
A couple was investigated for subfertility. Haemochromatosis was suspected when the 36-year-old man had failure of ejaculation, fatigue and limited facial hair growth. Haemochromatosis was confirmed by an iron saturation of 102% (normal range: 20-45), a highly elevated serum ferritin concentration of 5468 mg/1l (normal range: 18-280) and highly elevated liver enzymes. Molecular genetics showed homozygous C282Y mutation of the HFE gene. Due to consequent venesection therapy, levels of ferritin and transferrin decreased and liver enzymes normalized. However luteinizing hormone and follicle stimulating hormone failed to increase to normal levels. Treatment with gonadotropins was then applied, which corrected ejaculation and semen characteristics. His partner failed to become pregnant with ovulation stimulation and intrauterine inseminations. After two unsuccessful IVF procedures she became pregnant in the third procedure. Haemochromatosis should be considered and iron studies performed if subfertility due to an endocrine disorder is being investigated. Deposition in the pituitary or the gonads of the HFE-mutated patients leads to hypogonadism. Most of the patients with C282Y mutation are homozygous (85-90%), but the majority of the carriers will not develop the disease. Deficiency of hepcidin, an important regulator for the iron metabolism, was suspected in our patient, based on the early onset of his disease and the low serum levels of hepcidin. The age at diagnosis and the start of venesections is critical for reversal of organ damage. Aggressive venesection can restore hypothalamic-pituitary-gonadal function, preventing further organ damage. But with increasing disease progression venesection will not restore azoospermia or the failure to ejaculate.
Subject(s)
Erectile Dysfunction/etiology , Hemosiderosis/complications , Infertility, Male/etiology , Phlebotomy , Adult , Ejaculation/drug effects , Ejaculation/physiology , Erectile Dysfunction/therapy , Ferritins/blood , Follicle Stimulating Hormone/blood , Gonadotropins/therapeutic use , Hemosiderosis/genetics , Hemosiderosis/therapy , Humans , Hypogonadism/etiology , Hypogonadism/therapy , Infertility, Male/therapy , Liver/enzymology , Luteinizing Hormone/blood , Male , Testosterone/bloodABSTRACT
OBJECTIVE: To investigate whether a desire for pregnancy changed after etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine (EMA/CO) treatment for gestational trophoblastic disease and whether the incidence of infertility and adverse pregnancy outcome differed from the general population. DESIGN: A cohort study was performed. Data were collected from hospital records and questionnaires. SETTING: The study was carried out in referral hospitals in The Netherlands. POPULATION: All women registered by the Dutch Working Party on Trophoblastic Disease and treated with EMA/CO were included. METHODS: A questionnaire was sent to all surviving patients treated with EMA/CO from 1986 until 1997. Women who underwent a hysterectomy were excluded from the study. MAIN OUTCOME MEASURE: Pregnancy outcome and pregnancy wish after chemotherapy. RESULTS: Fifty patients were treated with EMA/CO. In 86%, a complete remission was achieved. A questionnaire was sent to 33 patients. Response rate was 82% (27/33). After EMA/CO, 18 of the patients experienced a regular menstrual cycle. Three patients had an amenorrhoea. Fourteen patients had a pregnancy wish. Twelve patients conceived; 21 pregnancies occurred. Sixteen pregnancies were term deliveries. Two pregnancies ended in a miscarriage and two congenitally abnormal children were delivered prematurely. CONCLUSION: After EMA/CO, 86% of women with a pregnancy wish achieved pregnancy. However, women can be so anxious about a new pregnancy that they refrain from it. A causative relation between the two congenitally abnormal children and EMA/CO cannot be determined because of the small sample. The rate of miscarriages is not higher than in the general population. We can reassure patients that pregnancy after EMA/CO has a high probability of success and a favourable outcome. To diminish the fear of getting pregnant in some patients, psychosocial care should be considered in addition to medical care.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hydatidiform Mole/psychology , Motivation , Pregnancy/psychology , Uterine Neoplasms/psychology , Adult , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Anxiety/etiology , Attitude to Health , Cohort Studies , Cyclophosphamide/administration & dosage , Dactinomycin/administration & dosage , Etoposide/administration & dosage , Female , Humans , Hydatidiform Mole/drug therapy , Methotrexate/administration & dosage , Middle Aged , Netherlands , Pregnancy Outcome , Prognosis , Uterine Neoplasms/drug therapy , Vincristine/administration & dosageABSTRACT
This prospective, randomized, 'blind' study with guinea-pigs was performed to assess the possible benefit of 6% dextran 70 (molecular weight 70 000) in the prevention of post-operative intra-abdominal adhesions and recurrent adhesions after adhesiolysis. In 50 guinea-pigs lesions for inducing adhesions were applied at the end of the uterine horn. On the right side a strip lesion was made and on the left side an end-to-end anastomosis was performed after section. Before closing the peritoneum 20 ml 6% dextran 70 (N = 25) or saline (N = 25) were introduced into the peritoneal cavity. A second laparotomy 4 weeks later showed no differences in adhesion formation in the animals treated with 6% dextran 70 and saline. In the animals with adhesions adhesiolysis was performed and 6% dextran 70 or saline was left in the peritoneal cavity. Again no beneficial effect of dextran was seen. The end-to-end procedure appeared to be far more suitable for producing adhesions than was the strip lesion.