Maintenance treatment with interferon for advanced ovarian cancer: results of the Northern and Yorkshire gynaecology group randomised phase III study.

A randomised phase III trial was conducted to assess the role of interferon-alpha (INFalpha) 2a as maintenance therapy following surgery and/or chemotherapy in patients with epithelial ovarian carcinoma. Patients were randomised following initial surgery/chemotherapy to interferon-alpha 2a as 4.5 mega-units subcutaneously 3 days per week or to no further treatment. A total of 300 patients were randomised within the study between February 1990 and July 1997. No benefit for interferon maintenance was seen in terms of either overall or clinical event-free survival. We conclude that INF-alpha is not effective as a maintenance therapy in the management of women with ovarian cancer. The need for novel therapeutics or strategies to prevent the almost inevitable relapse of patients despite increasingly effective surgery and chemotherapy remains.

Site specific lymph node metastasis in carcinoma of the cervix: Is there a sentinel node?

Follow-up for at least 5 years was available for 350 cases of stage IB and IIA carcinoma of the cervix managed by radical hysterectomy and pelvic lymphadenectomy. Lymphadenectomy technique mapped the patterns of pelvic lymph node metastasis (LNM). The effects on survival of specific factors relating to the lymphadenectomy (node count, number of positive nodes, site of positive nodes, number of sites positive, location of highest positive node) were determined for 80 women with LNM. The location of metastatic disease did not significantly predict survival. The incidence of LNM was 23% and 47.5% of these women survived 5 years. Only 45% of cases with a solitary LNM survived 5 years and in 45% of these recurrence was outside the pelvis. With the exception of the presacral group, the finding of isolated LNM in any other group with metastasis to the left side of the pelvis conferred the worst prognosis. The pattern of LNM from early stage carcinoma of the cervix is therefore random and the concept of a sentinel node or group is not tenable.

Adenocarcinoma of the cervix: a regional retrospective study.

A retrospective study using data from the Yorkshire Cancer Registry was undertaken to investigate the incidence, characteristics and prognosis of cases of cervical adenocarcinoma in the Yorkshire Region. Three hundred and twenty-six women resident in the Yorkshire Region formed the basis of the study. The overall five year survival for adenocarcinoma of the cervix is 53%. This was influenced by stage, lymph node involvement and differentiation. 37 out of 122 surgically treated patients received inappropriate treatment. There is a need for improved data collection in the treatment of these patients. This lends weight to the argument that cancer of the cervix should be managed in cancer units.

Which cervical sampler? A comparison of four methods.

Four cytology sampling methods were compared in 1063 patients referred for colposcopy with a recent abnormal smear. A dyskaryotic smear of any grade was considered a positive result, though comparisons were limited to cases with a subsequent biopsy confirming CINII or III. There were no differences between the abilities of any of the four methods to detect higher grades of CIN (chi (2)3 = 4.603, P > 0.20). The presence or absence of endocervical cells in a smear was not significantly associated with any variation in success rate (chi (2)1 = 0.959, P > 0.30). The joint analysis of the four methods and the presence/absence of endocervical cells also showed no significant effects (chi (2)7 = 12.768, 0.1 > P > 0.05). In the latter analysis the trend towards a conventional level of significance was accounted for by the Aylesbury spatula giving a relatively high success rate when endocervical cells were present. The suggestion of advantage for the Aylesbury spatula merits further investigation.

Detection and measurement of DNA adducts in the cervix of smokers and non-smokers.

Smoking has been associated, on epidemiologic grounds, with an increased risk of cervical neoplasia. We have investigated this association, using laboratory-based methods. A 32P post-labeling assay was performed on 97 cervical biopsies to detect and measure DNA adducts (additional products formed by the covalent binding of potential chemical carcinogens to nuclear DNA). The specimens were taken from both normal cervices as well as the histologically normal regions of cervices with invasive and intraepithelial neoplasia. A detailed smoking history was obtained from each patient and correlated with an assay of cotinine level in urine. Characteristic smoking-related DNA adducts were found, and a significant difference in their levels was detected between current and non-current smokers (P = 0.017, Mann-Whitney test). There was also a highly significant trend in median adduct levels between the three tissue types (P < 0.002). We conclude that the finding of smoking-related cervical DNA damage is suggestive of a causal association between smoking and cervical neoplasia.

Lymphocele.

Lymphocele is a complication which will be familiar to the gynaecological surgeon, particularly the oncologist. It is also well recognised in association with urological pelvic surgery and renal transplantation. Occurrence of lymphocele has been described in relation to surgery in a wide variety of other areas including the mediastinum, axilla, neck, aorta and peripheral vasculature. Clearly many of these examples are unusual occurrences, but they serve to illustrate that this complication will be encountered occasionally by surgeons in any of a number of disciplines.

Decision analysis for best management of mildly dyskaryotic smear.

Should a woman with a mildly dyskaryotic cervical smear be referred for colposcopy or should the smear be repeated? One way to answer this question is to use decision analysis and compare the expected mortality and cost of each policy. Data for each component of the question were obtained from published work worldwide and were supplemented with an audit of mildly dyskaryotic smears in West Yorkshire, UK. 2 out of 1000 women with an initial mildly dyskaryotic smear will develop cancer if a conservative repeat smear policy is adopted in association with five-yearly cervical screening. This number can be reduced to 1.6 per 1000 if cervical screening is offered every three years. A policy of immediate referral for colposcopy is also associated with a subsequent cancer rate of 1.6 per 1000. Therefore, repeating the smear is almost as effective as an immediate referral to a colposcopy unit. Even if a five-yearly cervical screening programme is adopted, 2500 women with a mildly dyskaryotic smear will need to be referred for immediate colposcopy to save 1 additional cancer. A conservative policy is not financially cheaper: an average of six additional smears is required to save each colposcopy referral. Sensitivity analysis shows that the excess cost of the conservative policy increases exponentially as the risk of a subsequent cytological abnormality exceeds 60%. Local cytopathology laboratories should audit their recurrent dyskaryosis rate associated with borderline, mild, and moderate dyskaryosis before accepting the U-turn in the national recommendations.

Cancer of the cervix in women under 40 years of age, a regional survey, 1975-1984.

OBJECTIVE: To review the method and results of treatment of carcinoma of the cervix in women less than 40 years old. DESIGN: Retrospective review of all available case records. SETTING: Yorkshire Regional Health Authority. SUBJECTS: 428 women less than 40 years old treated for stage IB-IV carcinoma of the cervix between 1975 and 1984 inclusive. MAIN OUTCOME MEASURES: Overall survival by stage, effect of age, identifiable factors of prognostic significance, survival, grade 3 morbidity and pattern of recurrence in relation to treatment. RESULTS: The 5-year actuarial percentage survival by stage was 78.4 (IB), 54.4 (II), 18.4 (III) and 0 (IV). Identifiable factors of prognostic importance were stage, nodal metastases (P less than 0.001) and tumour grade (P less than 0.01). CONCLUSION: Primary surgical treatment for young women with early disease allows ovarian conservation and the avoidance of radiotherapy in 80% of them. Such treatment results in less local recurrence, particularly evident in patients with moderate or poorly differentiated tumours and a lower incidence of serious morbidity.

Extraction of DNA from exfoliative cytology specimens and its suitability for analysis by the polymerase chain reaction.

The extraction of DNA from archival exfoliative cytology samples would allow the molecular biological analysis of this readily available material using the polymerase chain reaction (PCR). We have quantitatively and qualitatively studied the extraction of DNA from a variety of cytological preparations. For both fresh and archival cervical smears, overnight incubation with proteinase K produces high yields of high molecular weight DNA, but simply boiling the samples produces DNA suitable for PCR amplification of a single copy gene. Increasing the proteinase K incubation to several days allows the extraction of DNA from fixed and stained archival cytology slides from a variety of sites. The extracted DNA was again suitable for PCR analysis. Fresh and archival cytological material can be utilized for molecular biological study of disease processes using PCR. Archival cytological material is probably the best source of DNA and RNA after stored frozen tissue.

Intra-operative diagnosis of lymph node metastases in gynaecological practice using imprint cytology.

The technique of imprint cytology has been described for the assessment of malignancy and correlates well with histology. Despite the simplicity, speed and excellent cellular detail the technique has still not been fully appreciated. We describe the value of the technique applied to intra-operative diagnosis of lymph node metastases in gynaecological malignancy. Four hundred and seventy five lymph nodes were examined using imprint cytology followed by routine histology. The technique of imprint cytology was found to have a zero false negative rate, 0.6% false positive rate and an accuracy of 99.3%. We advocate the consideration of this technique for the evaluation of cases with gynaecological malignancy as an alternative to frozen section histology.

The value of pre-operative intracavitary radiotherapy in patients treated by radical hysterectomy and pelvic lymphadenectomy for invasive carcinoma of the cervix.

Two hundred and twenty-four patients with invasive carcinoma of the cervix treated by radical surgery have been studied retrospectively to determine the impact of pre-operative intracavitary radiotherapy. Pre-operative radiotherapy made no difference to survival, the incidence of local recurrence, distant metastasis or complications.

A prospective trial of computed tomography in the staging of ovarian malignancy.

Thirty patients, thought clinically to have ovarian tumours, were studied prospectively by pre-operative computed tomographic (CT) scans of the abdomen and pelvis. In six patients (20%) small metastases in mesentery, omentum and on subdiaphragmatic peritoneum were not detected by the scans. CT did not improve the accuracy of staging or assist the surgeons by drawing their attention to disease which they might otherwise have missed. Although CT gives an elegant demonstration of anatomy, it is not an alternative to extended laparotomy in patients with ovarian tumours.

Cervical smear histories of 500 women with invasive cervical cancer in Yorkshire.

The smear histories of 312 women with cancer of the cervix have been determined. Eighty nine women had had at least one negative smear reported in the 10 years before a diagnosis of cancer and 14 had had more than one negative smear. Fifty six of the 89 women had had a negative smear in the three years preceding the diagnosis of cancer. The highest number of negative smears (61) reported was among the 115 women aged under 45. Fifty eight slides reported as negative were submitted to independent review; 13 were subsequently reported as negative, 11 as unsatisfactory, and 34 as abnormal. These findings may in part explain why in this region there has been a disappointing reduction in the incidence of clinically invasive cervix cancer, and our findings may also apply elsewhere. Nevertheless, the confirmed negative smears chiefly occurred within three years of clinical cancer, particularly in the younger women, and this finding suggests that these women may have a short preinvasive phase.

Postoperative deep vein thrombosis: identifying high-risk patients.

A prospective study was carried out to confirm the validity of a predictive index for patients at risk of developing deep vein thrombosis. The index, which correctly identified nine out of 10 patients and incorrectly identified seven out of 52 patients as being at risk, is based on five variable--namely, the euglobulin lysis time, serum concentration of fibrin-related antigen, age, percentage overweight for height, and presence of varicose veins. Thus a population of patients at particularly high risk of developing postoperative deep vein thrombosis may be identified preoperatively by means of this index, so that prophylaxis may be used more rationally.

Prophylaxis of postoperative deep vein thrombosis: selective use of low-dose heparin in high-risk patients.

Administration of prophylactic low-dose subcutaneous heparin to prevent postoperative deep vein thrombosis is expensive, entails treating many patients unnecessarily, and causes some side effects. By using a predictive index a population of patients who are at particularly high risk of developing postoperative deep vein thrombosis may be identified preoperatively. Prophylaxis was given only to these patients, resulting in an incidence of deep vein thrombosis of 3.8% compared with 16.1% in previous studies in which no specific prophylaxis was given. By limiting prophylaxis to the group of patients identified by the predictive index as being at high risk of developing postoperative deep vein thrombosis results may be obtained that are as good as those expected from treating the whole population. Thus many patients are saved from exposure to low-dose subcutaneous heparin.

Amniocentesis with and without ultrasound guidance.

The increasing use of amniocentesis requires that the technique be made as safe as possible. The results of 284 amniocenteses done under ultrasound control are presented and compared with the results of 140 amniocenteses performed without ultrasound control. The use of ultrasound guidance increased the success rate from 80 to 99.6 per cent and decreased the incidence of feto-maternal haemorrhage from 8.5 to 2.8 per cent. The incidence of blood-stained amniotic fluid was reduced from 43.5 to 17.6 per cent. The clinical significance of these findings is discussed and the results interpreted as indicating that amniocentesis done with ultrasound guidance is a safer and less traumatic procedure.