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Nursing practice in gestational trophoblastic disease

VOL: 96, ISSUE: 40, PAGE NO: 37

Sarah Strickland, BSc, RGN, is clinical nurse specialist in gestational trophoblastic disease, Charing Cross Hospital, London

Trophoblastic cells are the outer layer of cells responsible for finding attachment, food and nourishment from the placenta for the inner cells of the ovum that are going to form the foetus. They produce the pregnancy hormone human chorionic gonadotrophin (HCG).

Trophoblastic cells are the outer layer of cells responsible for finding attachment, food and nourishment from the placenta for the inner cells of the ovum that are going to form the foetus. They produce the pregnancy hormone human chorionic gonadotrophin (HCG).

In gestational trophoblastic disease (GTD), however, the normal regulatory mechanisms controlling the behaviour of trophoblastic tissue is lost. Consequently, this abnormal tissue continues to proliferate and may invade the myometrium, developing a rich blood supply and tumour emboli.

The World Health Organization has classified GTD into five categories (WHO 1983). Two of these are pre-malignant diseases:

- Complete hydatidiform mole;

- Partial hydatidiform mole.

Three are malignant diseases:

- Invasive mole;

- Gestational choriocarcinoma

- Placental site trophoblastic tumour.

Hydatidiform moles
Hydatidiform mole (HM) literally means a shapeless mass of watery vesicles. HM is described as a pregnancy, usually lacking an intact foetus, in which the placental villi are characterised by oedema and trophoblastic cellular proliferation.

Approximately 80% of patients enter remission after uterine evacuation, but 15-20% will develop a malignant form of GTD (Berkowitz and Goldstein, 1989).

The incidence in the UK is approximately 1 in 1,200 pregnancies. In reviewing epidemiological reports, significant risk factors associated with this GTD are advanced maternal age and previous molar pregnancy (Buckley, 1979).

Complete hydatidiform mole

Complete hydatidiform moles (CHMs) possess only paternal chromosomes with no evidence of a foetus (Fig 1) (Lewis, 1993). The uterus is likely to be large for dates, and theca lutein cysts are more common. The cysts, usually multicystic and six to 12cm in size, result from hyperstimulation of the ovaries by high circulating blood levels of HCG.

Partial hydatidiform mole

Partial hydatidiform moles (PHMs) are triploid, two sperm fertilise an egg resulting in 69 chromosomes (Fig 1). There is usually foetal development. Characteristically, the diagnosis of PHM is made after histological review of curettage specimens from presumed incomplete or missed abortions (Berkowitz and Goldstein,1997).

Invasive mole
Complete or partial moles that invade the myometrium are known as invasive moles. CHMs and PHMs differ in their invasive potential and propensity for malignant transformation, with CHMs posing a higher risk. Approximately 15% of patients with CHM and 0.5% of patients with PHM may be expected to develop persistent trophoblastic disease following uterine evacuation (Curry et al, 1975). This means that, despite uterine evacuation, the molar tissue continues to grow. Patients with invasive mole most commonly have metastases in the vagina and lungs (Lurain, 1990).

Gestational choriocarcinoma
Gestational choriocarcinoma (GTD) is a malignancy that arises from trophoblastic tissue of term pregnancies, ectopic pregnancies, spontaneous/induced abortions or molar pregnancies (Berkowitz et al, 1984). It occurs in approximately 1 in 50,000 pregnancies.

The primary symptoms are irregular vaginal bleeding, dyspnoea, neurological symptoms and abdominal pain. Choriocarcinoma invades and metastasizes early, particularly to lungs, brain and liver, so is often widespread at diagnosis. The metastases are highly vascular and cerebral and intestinal haemorrhage may be life-threatening, making early diagnosis critical.

Choriocarcinoma should be considered in any woman of reproductive age with widespread metastases of unknown origin, or cerebral or intra-abdominal haemorrhage. Serum concentrations of human chorionic gonadotrophin should be measured in all such patients (Bower et a1,1995). Cure rates are high, but treatment of choriocarcinoma after a live birth is associated with higher mortality. Eliminating the disease becomes more difficult as time passes.

Placental site trophoblastic tumour
Placental site trophoblastic tumour (PSTT) is a rare manifestation of GTD, which develops at the placental implantation site and will complicate any type of pregnancy (molar and full-term pregnancies). The symptoms can appear from weeks to years after termination of the pregnancy. HCG values are often low and certainly below those of other forms of GTD (Finkler, 1991).

Diagnosis of PSTT is variable: an alert pathologist may make a diagnosis on dilatation and curettage or on a hysterectomy specimen. Others maybe identified as PSTT due to resistance to chemotherapy instigated on suspicion of hydatidiform mole.

It has been found that PSTT which is extremely rare, does not respond to chemotherapy as favourably as other GTDs.

Diagnosis and treatment
Patients with a molar pregnancy may present with vaginal bleeding and the main differential diagnosis is of threatened or incomplete abortion. An ultrasound will then provide a diagnosis of GTD on the basis of characteristic grape-like vesicles and the absence of a foetus.

GTD is nearly always curable if appropriately managed; in most cases, fertility can be preserved. Most important is a rapid diagnosis so that treatment may be administered promptly. Analysis of large groups of patients with these rare diseases has allowed treatment intensity to be adjusted so that each patient receives the minimum required (Seckl and Newlands,1997).

Initial management
The initial management of the patient with a molar pregnancy is evacuation of the uterine cavity by dilatation and curettage (D&C). If there is molar tissue detected in the uterine cavity after the initial evacuation a second D&C may be indicated.

Once the diagnosis has been confirmed on histology, the patient needs to be registered for follow-up to determine whether or not the molar tissue is going to die out spontaneously or persist (Bagshawe, 1986). In the UK a nationwide service has been established. Patients are registered at three reference laboratories for serial HCG estimations, based at Dundee, Sheffield and the Charing Cross Hospital in London. Between 7% and 8% of patients registered on the hydatidiform mole follow-up require chemotherapy.

Chemotherapy
Indications for intervention with chemotherapy in patients with hydatidiform mole are shown in Box 1. Most patients with choriocarcinoma will require chemotherapy (Seckl and Newlands, 1997). Box 2 shows prognostic factors.

At Charing Cross Hospital, a prognostic scoring system is used to subdivide the patients into low and high risk. They then receive the appropriate chemotherapy regimen. Patients are admitted for the first three weeks of either therapy, principally because the tumours are highly vascular and may bleed profusely in this early period of treatment.

Serial serum HCG estimations are used to follow the disease's response to therapy. The HCG should fall to normal, <5. Therapy should then continue for a further six weeks to avoid relapse.

On completion of chemotherapy, patients need to be followed-up regularly for life with HCG estimations to confirm that their disease is in remission. Patients are advised not to get pregnant until 12 months after completing their chemotherapy. This minimises the potential capacity to produce foetal malformation from the treatment and avoids confusion between a new pregnancy or relapsed disease as the cause of a rising HCG. When a patient becomes pregnant it is important to confirm by ultrasound that the pregnancy is normal (Seckl and Newlands, 1997).

Fertility
The outcomes of subsequent pregnancies following chemotherapy are, thankfully, usually successful. Importantly, there is no increase in the incidence of congenital malformations.

Prognosis
All patients in the low-risk group can be expected to be cured of their GTD (Bagshawe et al, 1986). For high-risk patients, survival has progressively improved and is currently 86% (Bower et al, 1997).

The number of deaths from choriocarcinoma can be reduced by a greater awareness of the possibility that multiple metastases in a woman with an undiagnosed primary of childbearing age may be due to choriocarcinoma. The simple measurement of the HCG level in such individuals is a very strong indicator of choriocarcinoma and could help to hasten referrals for life-saving chemotherapy (Seckl and Newlands, 1997).

Sex and contraception
During treatment, sexual intercourse may take place, provided this does not cause or aggravate any bleeding. Pregnancy should be avoided until one year after treatment has finished. The patient and partner need to use a condom together with a spermicidal preparation. No other form of contraception is permissible.

Once the HCG has reached normal levels (below 5) the patient can use a hormonal preparation. An intrauterine device (coil) can be fitted six weeks after the end of treatment. The diaphragm will need to be refitted after treatment as the size of the cervix may have altered.

Nursing care and support
Admission for three weeks means leaving family at home, possibly including young children. Sexual relations may suffer. Fear, self-blame, spousal blame and guilt often follow. The woman expresses loss of sexual desire, which can continue after treatment has finished. This can be due to fear of pregnancy within the first year.

The partner may feel blame for the molar pregnancy and, because he is supporting the woman, often feels unable to express his own fears.

For women on high-risk chemotherapy, the intensity of treatment can be debilitating. Alopecia, fatigue and nausea impact significantly on these women who are young and often have small children to care for.

It is vital that nurses who care for these patients have knowledge of the disease. It is important to emphasise that despite the short-term difficulties, the long-term outlook is excellent.

At the end of treatment, these women will need encouragement to re-establish their normal lifestyle and relationships with their families.

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