Management of gestational trophoblastic disease in developing countries.

In Malaysia, the incidence of molar pregnancy and gestational trophoblastic neoplasia is 2.8 and 1.59 per 1000 deliveries, respectively; the disease is more common among the Chinese compared to the Malays and Indians. While uterine suction is the preferred method of uterine evacuation of hydatidiform mole, complete evacuation was not achieved at the first attempt in 25% of cases. Partial moles comprise 30% of all moles; these need follow up similar to that for complete moles as they are potentially malignant. In the management of invasive moles, chemotherapy should not be withheld in the presence of metastases or failure of regression of hCG. Placental site tumours are rare. Prophylactic hysterectomy and prophylactic chemotherapy are not recommended. However, in those patients with unsatisfactory hCG regression curves indicating 'at risk' in developing gestational trophoblastic neoplasia (GTN), 'selective preventive chemotherapy' appears appropriate. Chemotherapy remains the main modality of treatment for GTN. As tumour bulk and location of disease are important determinants in outcome, we categorized our patients into low, medium- and high-risk groups with survivals of 100, 98 and 61.7% respectively. Surgery and radiotherapy have a limited role.

Clinical usefulness of tumour markers.

Tumour markers are substances related to the presence or progress of a tumour. An ideal tumour marker is (1) detectable only when malignancy is present, (2) specific for the type and site of malignancy, (3) correlates with the amount of malignant tissue present and (4) responds rapidly to a change in tumour size. At present, no tumour marker fulfills all of the above criteria. The first part of the review discusses the clinical usefulness of the commonly requested serum tumour markers, namely, prostate-specific antigen (PSA), CA 19-9, carcinoembryonic antigen (CEA), CA 125, CA 15-3, human chorionic gonadotrophin (hCG) and alpha-foetoprotein (AFP). It is hoped that this review article will decrease the abuse and misuse of these commonly requested serum tumour markers. The second part of the review discusses the clinical usefulness of catecholamines and their metabolites, calcitonin, thyroglobulin, parathyroid hormone, prolactin, adrenocorticotrophic hormone, oestrogen and progesterone receptors, p53, HER-2/c-erbB2, BRCA1 and BRCA2.

Telomerase activation and human papillomavirus infection in invasive uterine cervical carcinoma in a set of Malaysian patients.

AIM: Telomerase activity was studied in invasive uterine cervical carcinoma to assess whether it was activated during cervical malignant transformation and to look for a possible association with human papillomavirus (HPV) infection in a set of Malaysian patients. METHODS: Histologically confirmed invasive cervical carcinoma and benign cervices were assayed for telomerase activity using a commercial telomerase polymerase chain reaction (PCR) enzyme linked immunosorbent assay kit. The same cases were subjected to PCR detection of HPV using type specific (HPV types 6b, 11, 16, and 18) followed by L1 open reading frame (ORF) consensus primers. RESULTS: HPV was detected in 18 (13 HPV-16, one HPV-6b, four only L1 ORF) of 20 invasive cervical carcinoma and one (only L1 ORF) of 19 benign cervices. Raised telomerase activity (A(450 nm) > 0.215) was detected in 11 cervical carcinomas, with A(450 nm) ranging between 0.238 and 21.790 (mean, 3.952) in positive squamous carcinomas, whereas A(450 nm) was only 0.222 in the one positive adenosquamous carcinoma. Five of 11 cervical carcinomas in stage I, three of six in stage II, both in stage III, and the only case in stage IV showed telomerase activation. Increased telomerase activity was noted in five of the 12 lymph node negative, five of the seven lymph node status unknown cases, and the one case with presumed lymph node metastasis. Ten of 18 HPV positive and one of two HPV negative cervical carcinomas showed telomerase upregulation. CONCLUSIONS: Telomerase is activated in invasive cervical carcinoma. Although larger studies are needed, there seems to be no clear association between telomerase upregulation and HPV status, although there is a suggestion of increased telomerase activity in squamous carcinomas and late stage disease.

Chien-Tien Hsu Memorial Lecture. Fertility and gynaecologic malignancies.

Fertility and gynaecological malignancies have an important relationship. A clear inverse relationship exists between family size and the incidence of ovarian and endometrial cancer. Current methods of fertility control have an influence on subsequent development of various gynaecological malignancies. A slightly increased risk of breast cancer has been reported in current users and those who had used hormonal contraceptives (OCs) within 10 years; this risk declined with time and disappeared after 10 years. Women who started OC before age 20 had a higher relative risk; the disease did not spread beyond the breast in the majority. Most studies found OC to reduce the risk of ovarian and endometrial cancer. The relative risks of squamous cell carcinoma and adenomatous carcinoma of the cervix have been reported to be 1.3 and 1.5, respectively in ever-users of OCs; however, the aetiology of cervical cancer is multifactoral. Several reports suggest the beneficial effect of tubal ligation and breast feeding in reducing the risk of ovarian cancer. Therapy of gynaecological malignancies may have an influence on subsequent fertility. Amenorrhoea developing after treatment of hydatidiform mole may be due to choriocarcinoma, recurrent mole or a normal pregnancy. Choriocarcinoma can also develop after a partial mole. The risk of fetal teratogenicity from chemotherapy is present only if conception occurs during or immediately following the treatment cycles. Fertility is not impaired following chemotherapy. Successful pregnancies have occurred in women who have had widespread GTD including cerebral metastases. In the young patient with gynaecological malignancy preservation of fertility is possible. Fertility-sparing surgery may be safe in early ovarian epithelial cancers and even in advanced germ cell tumours. Recently, the fertility-sparing surgery of radical trachelectomy and pelvic lymphadenectomy has been carried out for early invasive cervical cancer in young women. Gynaecological cancer occurring in pregnancy is uncommon; it presents the clinician with a difficult situation to manage. In most instances the cancer is treated as though the patient is not pregnant; the timing and mode of delivery needs individualization. The overall prognosis for breast cancer complicating pregnancy is poor. Survival in cervical cancers diagnosed antepartum is similar to the non-pregnant patient. Ovarian cancer in pregnancy has a good prognosis because of the early stage at diagnosis.

Management of the pregnant mother with malignant conditions.

A malignancy discovered in pregnancy is often difficult to manage; the optimal maternal therapy has to be balanced with the fetal well-being. Generally, the cancer is managed as though the patient is not pregnant. For the various site-specific cancers, surgery is the main modality of treatment; this should be individualized. Chemotherapeutic agents are highly teratogenic in the first trimester, with some adverse effects when used after 12 weeks' gestation. The overall survival rate for pregnancy-associated breast cancer is poor; the reasons for this are discussed. For cervical cancer, delivery by caesarean section appears to be the method of choice, with significantly better survival rates compared with those who deliver vaginally. Other gynaecological and non-gynaecological malignancies are discussed.

Epidural analgesia in primigravidae in spontaneous labour at term: a prospective study.

OBJECTIVES: To prospectively study the intervention rate, duration of labour, malpositions, fetal outcome, maternal satisfaction, voiding complications and adverse events in healthy primigravidae in spontaneous labour at term following epidural analgesia. METHODS: A prospective randomized study involving 55 patients in the epidural group and 68 in the control pethidine--inhalational entonox group. RESULTS: There were significantly more obstetric interventions (instrumental deliveries) in the epidural group (p < 0.01). The total duration of labour and the duration of the second stage was prolonged in the epidural group (p < 0.01). There were more malpositions at the second stage of labour in the epidural group (p < 0.02). There were no differences in fetal outcome (Apgar scores and Special Care Nursery admissions). Patients in the epidural group were consistently happier with their method of pain relief (p < 0.01). Two patients required blood patches while another 2 patients had persistent backache post epidural analgesia. CONCLUSION: Epidural analgesia in primigravidae in spontaneous labour at term led to an increased instrumental delivery rate, prolonged duration of labour, greater rate of malpositions in the second stage, increased oxytocin requirements but with no difference in fetal outcomes but with happier mothers as compared to the control group.

The acute abdomen and the obstetrician.

An acute abdomen in pregnancy can be caused by pregnancy itself, be predisposed to by pregnancy or be the result of a purely incidental cause. These various conditions are discussed. The obstetrician often has a difficult task in diagnosing and managing the acute abdomen in pregnancy. The clinical evaluation is generally confounded by the various anatomical and physiological changes occurring in pregnancy itself. Clinical examination is further hampered by the gravid uterus. The general reluctance to use conventional X-rays because of the pregnancy should be set aside when faced with the seriously ill mother. A reluctance to operate during pregnancy adds unnecessary delay, which increases morbidity for both mother and fetus. Such mistakes should be avoided as prompt diagnosis and appropriate therapy are crucial. A general approach to acute abdominal conditions in pregnancy is to manage these problems regardless of the pregnancy.

Large lower segment myoma--myomectomy at lower segment caesarean section--a report of two cases.

Uterine leiomyoma is found in approximately 2% of pregnant women. One in ten women will have complications related to myoma in pregnancy. Myomectomy during pregnancy especially at Caesarean section is much discouraged in the literature. We present here 2 cases of large uterine myoma, situated in the anterior aspect of the lower segment, complicating pregnancy at term. Myomectomy in both instances allowed delivery of the fetus through the lower segment, making vaginal delivery in subsequent pregnancies possible.

Recent trends in histological pattern of cervical carcinoma among three ethnic groups in Malaysia.

OBJECTIVE: To study the trend of different histological types of cervical carcinoma among the 3 major ethnic groups in Malaysia. METHODS: All invasive cervical carcinoma histologically diagnosed for the first time in 1991-1992 and 1996-1997 at the University Hospital, Kuala Lumpur (UHKL) were reviewed for the following parameters; age, ethnic group, histological category. RESULTS: One hundred and twenty-one and 145 cases were diagnosed in 1991-1992 and 1996-1997, respectively. During both periods, squamous was followed by adeno and adenosquamous carcinoma in frequency. Patients' mean ages ranged within the 4th decade for all 3 major histological types. Ethnically, an overall predilection for the Chinese was observed. While squamous carcinomas had declined among the Chinese and Malays, adenocarcinomas were noted to increase. The converse was observed among the Indians. CONCLUSIONS: Ethnically, cervical carcinoma showed a predilection for Malaysians of Chinese descent. A decreasing incidence of squamous with a worrying increasing trend of adenocarcinoma was observed, like in other populations studied.

The management of gestational trophoblastic disease in developing countries such as Malaysia.

Gestational trophoblastic disease is a common gynaecological problem in Malaysia. The incidence of molar pregnancy is 2.8 per 1000 deliveries, being more common amongst the Chinese. The preferred method of evacuation is suction curettage; complete evacuation of the uterus was not achieved at the first attempt in 25 per cent of cases. Partial moles in our centre comprised 30 per cent of all moles. This is potentially malignant and needs follow-up for a complete mole. In the management of an invasive mole, chemotherapy should not be withheld in the presence of metastases and failure of regression of hCG. The role of prophylactic hysterectomy and prophylactic chemotherapy in the management of molar pregnancy is discussed "Selective preventive chemotherapy" in patients at "risk" appears appropriate. Chemotherapy remains the main modality of treatment for gestational trophoblastic tumours (GTT). We categorised our patients into low, medium and high-risk groups; survivals were 100, 98, and 61.7 percent respectively. These patients when categorised according to FIGO staging had survivals of 100, 80, 78.6 and 68.2 per cent respectively for stages 1, 2, 3 and 4 respectively. The reasons for the poor survival in the 'high-risk' group are discussed. Colour doppler blood flow studies are now being carried out; its role needs further evaluation. Surgery and radiotherapy have only a limited role in the management of these cases.

Adjuvant chemotherapy in "high risk" patients after Wertheim hysterectomy--10-year survivals.

Although the primary operative mortality following radical hysterectomy for stage IB and early stage IIA cervical carcinoma is less than 1%, survival is poor in those patients with histological evidence of "risk" features--lymph node metastases, lymphatic vascular tumour permeation and clinically undetected parametrial metastases. In the 7-year period 1983 to 1989, 239 patients with stage IB and early IIA disease had radical hysterectomy and pelvic lymphadenectomy. One hundred and eight patients (45.2%) had various poor prognostic histological features and received adjuvant chemotherapy--70 had cisplatin, vinblastine, bleomycin (PVB), 16 had mitomycin C (MMC) and 22 others received mitomycin C + 5-fluorouracil (5-FU). Although not randomised, the risk factors present in each group were identical. These patients have now been followed up for periods ranging from 8 to 14 years. All recurrences, except one, occurred within 23 months of surgery; in the remaining this occurred 8 years later. This suggests that very close long-term follow-up is needed. Recurrences were markedly higher in the group who refused adjuvant chemotherapy (31.6%). The 10-year survival in patients without risk factors was 97.2%. In those patients with risk factors refusing adjuvant therapy it was 73.7%. The adjuvant chemotherapy group had a better survival of 86.1% (P = 0.001). The 10-year survivals in patients with positive nodes were similar--66.7% in the MMC group and 71.4% in the PVB group. The 10-year survival in patients with squamous cell carcinoma was significantly better (90.3%) in the mitomycin C (and MMC + 5-FU) group compared to the PVB group (80.1%) (P = 0.005). The 10-year survival in patients with adenocarcinoma and adenosquamous carcinoma was significantly better (96.3%) in the PVB group compared to those receiving MMC (and MMC + 5-FU) (57.1%) (P = 0.01). It would, thus, appear that the adjuvant chemotherapy of choice for patients with squamous cell carcinoma would be MMC (and MMC + 5-FU) and for those with adenocarcinoma, the PVB regime.

The management of gestational trophoblastic disease in developing countries such as malaysia.

Gestational trophablastic disease is a common gynaecological problem in Malaysia. The incidence of molar pregnancy is 2.8 per 1000 deliveries, being more common amongst the Chinese. The preferred method of evacuation is suction curettage; complete evacuation of the uterus was not achieved at the first attempt in 25 per cent of cases. Partial moles in our centre comprised 30 per cent of all moles. This is potentially malignant and needs follow-up for a complete mole. In the management of an invasive mole, chemotherapy should not be withheld in the presence of metastases and failure of regression of hCG. The role of prophylactic hysterectomy and prophylactic chemotherapy in the management of molar pregnancyis discussed "Selective preventive chemotherapy" in patients at "risk" appears appropriate. Chemotherapy remains the main modality of treatment for gestational trophoblastic tumours (GTT). We categorised our patients into low, medium and high-risk groups; survivals were 100, 98, and 61.7 percent respectively. These patients when categorised according to FIGO staging had survivals of 100, 80, 78.6 and 68.2 per cent respectively for stages 1, 2, 3 and 4 respectively. The reasons for the poor suvival in the 'high-risk' group are discussed. Colour doppler blood flow studies are now being carried out; its role needs further evaluation. Surgery and radiotherapy have only a limited role in the management of these cases.

Early congenital syphilis--a continuing problem in Malaysia.

Between February 1990 and May 1993, 13 cases of early congenital syphilis (ECS) were managed in the Paediatrics Unit, University Hospital, Kuala Lumpur. Twelve mothers were unbooked with 10 inborn babies. Only one mother had antenatal booking at this hospital but she defaulted antenatal follow-up. Several risk factors associated with ECS were identified: inadequate or no prenatal care (5/13), failure to repeat a serological test for syphilis in the third trimester when it was tested negative at first booking (5/13), sexual promiscuity, substance abuse and a past history of contracting sexually transmitted disease. All 10 mothers who had their serological test repeated at delivery were found to have a positive VDRL and TPHA. Adequate antenatal care early referral of infected, expectant mothers for treatment, and a repeat serological test for syphilis could have prevented these cases of ECS.

Aggressive angiomyxoma of the vulva with an unusual vascular finding.

We report the first documented Malaysian case of aggressive angiomyxoma (AAM) of the vulva. A 56-yr-old woman of Indian ethnic origin presented with a vulval lesion which was clinically mistaken for a Bartholin's cyst. The lesion was surgically excised and a diagnosis of AAM was made histologically. Of particular interest was the finding of foamy and mononuclear inflammatory cells and fibrin in the walls of most of the lesional blood vessels. The patient recovered uneventfully and remains without tumor recurrence at the time of writing 37 mths after initial presentation.

Radical hysterectomy and pelvic lymphadenectomy for early invasive cancer of the cervix - 14-year experience.

During a 14-year period, 397 radical hysterectomies and pelvic lymphadenectomies were performed for early invasive carcinoma of the cervix. Twenty-one patients were in stage IA2 with lymphatic/vascular channel permeation (5.2%), 340 in stage IB (85.6%) and 34 in early stage 2A disease (8.5%). Eighteen patients (4.5%) were pregnant. Adenocarcinoma comprised 26.9% of cases. The mean operative time was 4.14 h; the intraoperative blood loss was less than 1.51 in 77.3% patients. There was no operative mortality; one patient died 3 weeks after surgery from clostridium difficile enterocilitis. Eleven patients (2.7%) developed venous thrombosis; severe lymphedema occurred in four (1%). The incidence of uretero-vaginal fistula was 0.2% and that of vesico-vaginal fistula 0.5%. Ovarian metastases were noted in 4.3% of cases with adenocarcinoma. Sixty-six patients had positive nodes (16.6%). Five-year survival in patients with more than 2 positive nodes was 68%. The use of adjuvant chemotherapy in patients with 'high risk' factors resulted in survival rates approaching those without risk factors. Neo-adjuvant chemotherapy was used in 10 patients with large bulky tumors; the results were favorable. Recurrences occurred in 47 patients (11.8%); 36 patients have died (9.1%). Age did not appear to influence survival. The overall 5-year survival was 92.2%.

Hydatidiform molar pregnancy in Malaysian women: a histopathological study from the University Hospital, Kuala Lumpur.

A review of gestational trophoblastic disease diagnosed at the Department of Pathology, University Hospital, Kuala Lumpur from January 1989 to December 1990 using established histological criteria showed 25 complete hydatidiform moles (CHM), 11 partial hydatidiform moles (PHM), 1 invasive mole and 2 choriocarcinoma. The ages of the patients with CHM ranged from 21 to 43 years (mean = 28.5 years) and PHM 20 to 33 years (mean = 27.5 years). The invasive mole occurred in a 42-year-old Malay woman. The two patients with choriocarcinoma were both Chinese and 41 and 46-years old respectively. During the same period, 1,062 non-molar abortions and 13,115 births, inclusive of livebirths and stillbirths were recorded at the University Hospital. The incidence rate of hydatidiform moles was thus estimated to be 1:384 pregnancies. PHM constituted 30% of all molar pregnancies. Hydatidiform moles occurred among the Malays, Chinese and Indians at the rate of 2.43, 2.66 and 3.29 per 1,000 pregnancies respectively. It appears that hydatidiform molar pregnancy has the highest prevalence among the Indians, a finding similar to an earlier Singapore study.

Surgical management of early invasive cancer of the cervix associated with pregnancy.

The simultaneous occurrence of carcinoma of the cervix in pregnancy is uncommon. In a prospective study of 397 patients undergoing type III radical hysterectomy for early invasive cancer of the cervix, 18 were pregnant at the time of surgery; 4 of these were operated after delivery elsewhere. Two others had a type I extrafascial hysterectomy. The incidence was 1 in 4077 deliveries. The clinical and histological characteristics of these patients are presented. Routine speculum examination and cervical cytology in all pregnant patients early in pregnancy are vital for early diagnosis. Bleeding in pregnancy should not automatically be assumed to be caused by pregnancy-related conditions. The strategies in surgical management are discussed. Radical hysterectomy in pregnancy is safe. No major complications were encountered; the mean blood loss was 1.4 liters. The incidence of pelvic node metastases was similar to that seen in nonpregnant patients. The overall 5-year survival rate was 77.7%. Of the 4 patients who died, 3 presented in the puerperium; all succumbed within 27 months. Poor histological prognostic features contributed to the significantly poorer survival in the puerperal patients (P = 0.0445). The 5-year survival in those presenting during the antepartum period (92.8%) was, however, similar to that in the nonpregnant patients. Metastases to the placenta or fetus were not encountered.