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Keywords:

  • Gestational trophoblastic disease;
  • hysterectomy;
  • lymphadenectomy

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

We reviewed 25 cases of gestational trophoblastic tumours referred for surgical management from Charing Cross Hospital (the London centre for gestational trophoblastic disease [GTD]) over a 13-year period. The operation performed was total abdominal hysterectomy, with lymph node sampling in 9/25 (36%) women and bilateral salpingo-oophorectomy in 11/25 (44%) women. Radical hysterectomy and unilateral parametrectomy was required in 3/25 (12%) women. Three of 25 (12%) women failed to survive, i.e. the overall rate of survival was 88%. Management by hysterectomy of primary drug-resistant and relapse cases of GTD is a useful and safe adjunct to chemotherapy.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

Gestational trophoblastic disease (GTD) includes a spectrum of cellular proliferation of trophoblast ranging from the various forms of hydatidiform mole (complete and partial) through invasive mole and the malignant trophoblastic tumour choriocarcinomas to placental site trophoblastic tumours (PSTT). Gestational trophoblastic tumours (GTT) is the term used to denote those conditions that require more active intervention, usually chemotherapy, and includes invasive mole, choriocarcinomas and placental site tumours.

One of the main reasons for current treatment success is the inherent chemosensitivity of GTD and GTT. The vast majority of women with GTD will respond to evacuation of the uterus plus or minus chemotherapy if human chorionic gonadotrophin (hCG) levels remain elevated. Chemotherapy produces high cure rates while maintaining fertility, allowing women to have further pregnancies. For the small minority whose hCG levels remain elevated despite chemotherapy, more definitive surgical management may be required, e.g. a total abdominal hysterectomy (TAH).

The main reasons for the successful outcome in women with GTD and GTT are the following:

  • 1
    Registration and follow up of women at risk.
  • 2
    GTD and GTT always produce hCG, allowing screening, monitoring treatment and follow up.
  • 3
    Inherent chemosensitivity of GTD and GTT.
  • 4
    Centralisation of expertise so that treatment can be optimised and further advances made.

The main causes of treatment failure are the following:

  • 1
    Early deaths from initial disease extent at the time of presentation.
  • 2
    Development of drug resistance.
  • 3
    PSTTs behave unpredictably and may not be chemosensitive.

Therefore, surgical management plays an important role after chemoresistance of the tumour during the initial treatment episode. Surgery can also be an important component of salvage treatment (progression of disease after primary treatment) and often may be clearly therapeutic. Surgery plays a significant part in the primary treatment of women with PSTT because PSTT has rather variable chemosensitivity. Hysterectomy is the treatment of choice for PSTT limited to the uterus.

Our objective was to review the role of surgery in the management of GTD and GTT cases referred to the Chelsea and Westminster Hospital and to West London Cancer Centre, Hammersmith Hospital NHS Trust from the London Centre for Trophoblastic Tumours at Charing Cross Hospital, over a 13-year period (March 1993 to January 2006).

NameTo whom referredDate of surgery
AgeWho referredHistology
ParityPast medical historyPostoperative management
Last pregnancyReferring problemPregnancies postsurgery
AddressReferring β-hCGSurvival outcome
Year referredOperation performedLatest β-hCG

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

The data were compiled using the case records from both sites and the clinical treatment and information computer system at Charing Cross Hospital. A prototype data sheet was compiled to obtain the following information (as illustrated below) for each woman:

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

Nine (36%) of the referred cases were choriocarcinomas, six (24%) were PSTT and ten (40%) were hydatidiform moles.

The two main reasons for referral for surgical management were chemoresistance of the tumour during the initial treatment episode and relapse after treatment.

The median age of women at presentation was 38 years (range 23–61 years), and ten women were older than 40 years. Twenty-one of our women were parous and four were nulliparous. The median interval from pregnancy to diagnosis was 34 months (range 4 months to 30 years).

After extensive preoperative imaging to identify nonpelvic disease, the women’s staging was as follows: 14 women were at stage I, three were stage II, six were stage III and two were stage IV.1 In the metastatic group, six women were in high-risk and two were in low-risk group. The lungs were the most common site of metastases. All women with distant metastases had pulmonary disease, and two had liver metastases.

The median serum β-hCG level at diagnosis was 3237 iu/l (range 18–43 694 iu/l), but 11/25 women had β-hCG levels of less than 500 iu/l.

TAH was performed in all 25 women, with lymph node sampling in 9/25 (36%) women and bilateral salpingo-oophorectomy in 11/25 (44%) women. A radical hysterectomy and unilateral parametrectomy were required in 3/25 (12%) women. In some of these cases, selective vessel ligation and ureteric stenting were proved useful. No significant intra or postoperative complications were noted, and all women had normal postoperative recovery.

The final histology reports included eight cases of PSTT, ten of choriocarcinoma, four of hydatidiform mole and three cases with nonviable trophoblast identified.

Postoperatively, 4/25 women did not receive adjuvant chemotherapy, two because their surgical treatment came after the completion of their chemotherapy scheme and two because no viable trophoblast was identified in their surgical specimens.

Despite having a hysterectomy followed by chemotherapy, 3/25 (12%) women, all in the high-risk metastatic group, failed to survive. Their outcome was unrelated to the surgery. The first woman died in June 1994 approximately 15 months after hysterectomy (TAH) for a chemoresistant choriocarcinoma, and she was at FIGO stage IV with lung and liver metastases. The second death was of an HIV-positive woman with choriocarcinoma who underwent a hysterectomy and right pelvic lymphadenectomy for tumour recurrence on the right side of uterus and died 12 months after surgery from chemoresistant disease and lung metastases. The third death occurred approximately 5.5 months after a simple TAH for a chemoresistant PSTT with lung metastases. These were the only three cases where postoperative β-hCG values remained high or even higher than the value before the operation. In all the other cases, β-hCG values dropped to normal levels as shown in Figure 1.

image

Figure 1. HCG responce to chemotherapy and surgery. CO, cyclophosphamide and vinctistine; EMA, etoposide, methotrexate and actmomycin D; EP, etoposide and cisplatin; MTXFA, methotrexate and folinic acid; Rx, treatment.

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Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

Management of trophoblastic disease in the first instance involves evacuation of the uterus. In the presence of persistently elevated β-hCG levels or continuing problems with haemorrhage, further evacuation may be necessary preferably under ultrasound guidance. This should normally be discussed with a GTD centre because of the risk of perforation, haemorrhage or infection. Thereafter, if the β-hCG levels remain elevated, chemotherapy should be instituted. The vast majority of women will respond to these measures because of the inherent chemosensitivity of GTD.

For the small minority whose β-hCG levels remain elevated after chemotherapy, more definitive surgical management may be required, in the form of TAH. Over the 12 years and 10 months of the period reviewed, March 1993 to January 2006, out of 11 213 women who were registered at the Charing Cross Centre for Trophoblastic Disease, 25 were referred to the authors at the Chelsea and Westminster Hospital and latterly at the West London Gynaecological Cancer Centre, Hammersmith Hospital NHS Trust, for surgical management of gestational trophoblastic disease with abdominal hysterectomy. In addition to the 25 cases referred to the authors, other cases have been referred back to the referring surgeons or to Hammersmith Hospital NHS Trust prior to the institution of the West London Gynaecological Cancer Centre. It is, therefore, not possible to give the percentage of overall patients who have required surgery. Many centres have published their experience in the management of GTD by hysterectomy, with an incidence ranging from 1.5 to 35%.2–4

Preoperative assessment should include Doppler flow ultrasonography of the pelvis, computed tomography and/or magnetic resonance imaging (MRI) scans of the chest, abdomen and pelvis and MRI of the head. A β-hCG, full blood count and blood biochemistry measurements should be performed together with the cross-match of 2–6 units of blood. TAH in the presence of choriocarcinoma can prove very taxing. Uterine vascularity may be massively increased, and the uterine arteries may be up to 1 cm in diameter. More troublesome still is the massive enlargement of the uterine venous plexus. This can lead to significant haemorrhage during ureteric dissection, particularly in cases where the tumour has spread into the parametrium. The necrotic nature of the tumour and the vascular enlargement make it difficult to obtain haemostasis, and severe bleeding can ensue. The authors have found it useful in the presence of extrauterine spread to perform ureteric stenting. In women with excessive vaginal bleeding, arterial embolisation may be considered if maintenance of fertility is desired.

Laparotomy is performed, generally via a Pfannenstiel incision, but may require Cherney’s muscle cutting or a midline incision depending on the surgeon’s preference and the size of the uterus. In the presence of huge vessels, the authors have found it useful to commence the procedure by opening the broad ligament, identifying the ureter and dissecting it superiorly as far as the bifurcation of the common iliac artery. Vascular elastic slings can be placed around the internal iliac vessels. These vessels can be temporarily ligated prophylactically or the slings can be left loose until the need arises. These slings have proved useful to the authors in the face of the torrential haemorrhage which can arise. Dissection of the internal iliac arteries is then performed until the origin of the uterine arteries is identified. These are then skeletonised and ligated using either polyglactin ties or surgical clips. The multiple uterine veins are ligated using surgical clips (Liga). If a PSTT is suspected, removal of the pelvic lymph nodes and para-aortic nodes is advisable for gross lymph node disease. In our series, 1/6 (16.6%) women originally referred with PSTT had positive lymph nodes. In the total Charing Cross Hospital series, 3/48 (6.25%) women with PSTT had lymph node involvement. In women with choriocarcinoma, lymph nodes are involved in less than 0.5% (M. Seckl, pers. comm.).

Excessive uterine manipulation should be avoided when possible so as to reduce any possible risk of embolisation with trophoblastic tissue. Some centres use prophylactic chemotherapy at the time of hysterectomy, which is not our policy. Because these women may be haemodynamically unstable, it is recommended that these procedures should be carried out by an experienced surgical team at a specialised centre providing full medical support, including intensive care unit. In our series, no serious intra or postoperative complications were reported.

The majority of women (15/25 [60%]) in our review were women younger than 40 years (i.e. in their childbearing years), and therefore, the psychological impact from the loss of their fertility should not be underestimated. In our women who underwent TAH, 21 were parous and 4 were nulliparous. Two nulliparous women were among those who failed to survive because of chemoresistant disease and lung metastases.

Surgery has also been used in the management of metastatic disease. Localised metastatic disease in the lung can benefit from surgical resection with either lobectomy or partial thoracotomy.5,6 In our series, six women had thoracotomies during their follow-up period because of lung metastases.

In 22/25 women, the operation was therapeutic as shown by the negative or almost negative β-hCG values obtained postoperatively. During the follow up of the remaining three women, we detected significant rise in β-hCG values. Unfortunately, all these three women died within 1 year after the operation. These women had initially presented with metastatic disease, and so in retrospect, they did not benefit from hysterectomy because of the presence of occult metastatic disease at the time of surgery.

Conclusion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

Management of primary drug-resistant and relapse cases of GTT by hysterectomy is a useful and safe adjunct to chemotherapy and has a satisfactory long-term outcome (88% survival).

Hysterectomy may be required for the management of excessive uterine bleeding either at presentation or after the onset of chemotherapy and in the management of chemoresistant disease localised to pelvis. It is the treatment of choice in the management of PSTT confined to the uterus.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References