Cervical cancer still presents symptomatically 20 years after the introduction of a structured national screening programme.

OBJECTIVE: To investigate the pattern of presentation of cervical cancer and to identify the characteristics of women who present symptomatically with cervical cancer. METHODS: A retrospective study of all cervical cancer cases diagnosed over a 4-year period. Details of mode of presentation, stage at diagnosis and cytological/gynaecological history were collated. RESULTS: In total, 148 cases were identified with a median age of 46 years (range, 20-91 years). In this population, 112 (75.7%) women were within the screening age range. Forty-eight (33.6%) were asymptomatic at diagnosis and presented through the colposcopy clinic. All asymptomatic women (100%) had stage I disease at diagnosis, compared with 37.2% of the symptomatic group (P < 0.001). Postmenopausal bleeding was the most common presenting symptom (33%), followed by postcoital bleeding (14.2%), intermenstrual bleeding (12.2%) and increased vaginal discharge (3.4%). The majority of symptomatic women presented through colposcopy, gynaecological oncology or gynaecology clinics (87.6%); however, 6.5% presented through the emergency department. Women who presented symptomatically were significantly older than asymptomatic women (54.9 versus 38.1 years, P < 0.001). Women at risk of social isolation (non-English speakers, alcohol abusers, heavy smokers, receiving treatment for psychiatric disease) were more likely to present with symptoms, through the emergency department and with advanced disease at diagnosis (stage II+) (P < 0.001). CONCLUSIONS: A review of local cervical cancer cases can highlight areas of weakness in a screening programme and can identify populations who are at risk in presenting symptomatically with advanced disease.

A distinctive vulval fibroma of so-called prepubertal type in a postmenopausal patient.

The case of a 65-year-old female patient who has had a large right vulval mass for over 30 years is reported here. The mass was excised, but the hypocellular mesenchymal tumour was difficult to classify histologically. On further specialist assessment, it was found to be identical to the recently recognised distinctive prepubertal vulval fibroma. These are very rarely reported in children, and till now, has never been reported in an adult.

Biodistribution of (111)indium-labeled engineered human antibody CTMO1 in ovarian cancer patients: influence of protein dose.

Thirty-one patients suspected of having ovarian cancer received a single i.v. injection of radiolabeled (100 MBq (111)In) engineered human CTMO1 (hCTMO1) to investigate its potential as an internalizing drug carrier. hCTMO1 is a complementary-determining region-grafted human IgG4 monoclonal antibody recognizing an ovarian carcinoma-associated antigen, the MUC-1-gene product. The amount of radioactivity was determined in tumor tissue, various normal tissues, including liver biopsies, and blood samples obtained at laparotomy, 6 days after injection of either 0.1 or 1.0 mg hCTMO1/kg of body weight. Circulating antigen-15-3 was measurable in all patients before injection, and immune complex formation was already present at the end of infusion. In the 0.1 mg/kg group, most of the radioactivity was bound to immune complexes, whereas in the 1.0 mg/kg group, most was bound to IgG monomers. Increasing the hCTMO1 dose 10-fold did not influence the overall disappearance of (111)In from the blood, but the elimination half-life of (111)indium bound to immune complexes was increased 2-fold. Uptake in tumor tissue 6 days postinjection at the 0.1 mg/kg dose was 7.6 times higher (P = 0.0009) than in normal tissue and 2.5 times higher (P = 0.03) than in blood. At the 1.0 mg/kg dose, the uptake in tumor tissue was 14.0 times higher (P = 0.0003) than in normal tissue and 8.1 times higher (P = 0.0007) than in blood. Liver activity was substantial (23.7 +/- 10.5 and 18.3 +/- 6.7% of the injected dose/kg for the 0.1 and 1.0 mg/kg dose group, respectively). These results are superior to those found with other clinically tested anti-MUC-1 gene product antibodies. hCTMO1 seems to be a suitable carrier for cytotoxic agents in ovarian carcinoma patients; the better uptake results and tumor-to-blood ratios are obtained at the higher dose of 1.0 mg hCTMO1/kg body weight.

Characterisation of a thermophilic L-glutamate dehydrogenase biosensor for amperometric determination of L-glutamate by flow injection analysis.

Carbon paste wax electrodes incorporating thermophilic L-glutamate dehydrogenase, NADP and a polymeric toluidine blue O (poly-TBO) mediator have been characterised for the amperometric determination of L-glutamate at 313-318 K in a flow injection analysis (FIA) system. The biosensors exhibit good sensitivity, mechanical stability and reproducibilty, unlike carbon paste- or carbon wax-based electrodes under the same conditions. The carbon paste wax electrode responds linearly to L-glutamate up to 40 mM, the detection limit is 0.3 mM and the RSD (n = 10) for 5 mM L-glutamate was 7.6%. The response to some potential interferents has been quantified. Addition of finely ground hexaammineruthenium (III) trichloride ([Ru(NH3)6]Cl3) to the carbon paste wax electrodes decreases the FIA peak width and increases the peak current. The metal complex appears to accelerate the rate of oxidation of NAD(P)H by poly-TBO.

Ectopic prolactin secretion secondary to an ovarian tumour.

UNLABELLED: Ectopic hormone secretion is a well-recognised phenomenon; however, ectopic prolactin secretion is exceptionally rare. Hoffman and colleagues reported the first ever well-documented case of ectopic prolactin secretion secondary to a gonadoblastoma. We report a lady who presented with galactorrhoea and a large ovarian tumour that was found to secrete high levels of prolactin. LEARNING POINTS: Aim of this case report is to highlight the occurrence of this condition.Lack of awareness can often lead to a diagnostic conundrum.

Should women with postcoital bleeding be referred for colposcopy?

This study was to determine the risk of finding significant cervical pathological abnormality in women referred to the colposcopy clinic primarily because of postcoital bleeding. We evaluated the cervical smear history of such women and correlated this with any colposcopic or pathological abnormality. There were 142 women seen over a period of 12 months. The age range of the study population was 16 - 61 years (mean age of 34.1 years). There was no case of lower genital tract invasive neoplasia. Out of the 142 cases, 56 women (39.4%) had normal findings at colposcopy and 44 (31%) were secondary to cervical ectopy. A total of 27 (19%) had cervical intraepithelial neoplasia (CIN) out of which there were 15 (10.6%) cases of high-grade disease (CIN II and CIN III); and, 20 (74%) out of the 27 women with CIN had a recently negative cervical smear (within the previous 36 months). Seven women (4.9%) had benign cervical polyps that were removed during colposcopy. The frequency of finding invasive lower genital tract neoplasia in women with postcoital bleeding is low. However, a good proportion of them would have a diagnosis of cervical intraepithelial neoplasia even with a recently negative cervical smear. Therefore, postcoital bleeding should remain an indication for referral to the colposcopy clinic for a detailed evaluation of the lower genital tract.

Aggressive angiomyxoma of the perineum.

We report the case of perineal aggressive angiomyxoma in a 46-year-old woman presenting as left perineal swelling associated with superficial dyspareunia. Initial clinical examination revealed a 4- to 5-cm cystic mass in the posterior aspect of the left labia majora, not thought to be typical of a Bartholin cyst. A magnetic resonance imaging (MRI) scan revealed a well-defined 2- x 1.5- x 2-cm area posterolateral to the lower vagina on the left but anterolateral to the anal canal extending into the left ischiorectal fossa, with no obvious involvement of the anal sphincter complex. Excision biopsy was performed via an incision in the left labia majus under general anesthesia. Histologic findings were consistent with aggressive angiomyxoma of the vulva. This was confirmed by immunohistochemistry showing spindle cells positive for vimentin with strong nuclear staining for estrogen and progestogen receptors. Postoperative management following discussion at the multidisciplinary gynecological oncology meeting was to perform a repeat MRI scan 6 weeks postoperatively, and treatment with raloxifene was commenced for its antiestrogenic property.

Urological problems and the treatment of gynaecological cancer.

This article reviews the recent literature on urological complications in gynaecological oncology. In particular it focuses on the current controversies in the management of urinary fistulae and reconstruction or urinary diversion after pelvic exenteration.

The effect of circulating antigen on the biodistribution of the engineered human antibody hCTM01 in a nude mice model.

Clinical studies are currently underway to assess the biodistribution and therapeutic potential of the genetically engineered human antibody hCTM01 directed against polymorphic epithelial mucin (PEM) in patients with ovarian carcinoma. The present study was undertaken to assess the effect of circulating PEM antigen on the biodistribution of the anti-PEM antibody in mice bearing MUC-1 transfected adenocarcinoma cell lines. Tumour xenografts were established from three cell lines: 413-BCR, which expressed antigen on the cell surface and also shed antigen into the circulation, E3P23, which expressed the antigen but did not shed into the circulation, and a negative control (410.4 MUCI). Groups of five mice were injected with 1.0 mg/kg antibody, imaged after 72 h and then sacrificed, followed by assay of tissue uptake. The results showed a clear difference in the tumour and liver uptake, with the non-secreting cell line showing almost twice the tumour uptake and approximately 20% of the liver uptake of the secreting cell line.

Patient satisfaction with daycase laparoscopy.

A prospective audit was performed on all patients preselected for daycase surgery over a 3-month period. The aim of the study was to evaluate patient acceptability and satisfaction with laparoscopy performed as a daycase procedure. Patients completed standard questionnaires before operation and at 4 weeks after surgery. Questions included satisfaction with daycase surgery, subjective pain experience, time taken to resume normal activities, adequacy of analgesia and necessity to call general practioners. Analysis of results revealed that 69% of patients were satisfied with day surgery laparoscopy. However there were highly significant differences (P less than 0.001) between resumption of normal activity, pain experienced and length of stay between patients satisfied and dissatisfied with daycase surgery. This study suggests that guidelines for daycase procedures may be overambitious as 31% of patients already pre-selected, were dissatisfied with daycase surgery.

An immunoscintigraphic evaluation of the engineered human monoclonal antibody (hCTMO1) for use in the treatment of ovarian carcinoma.

OBJECTIVE: To assess the safety and targeting ability of the engineered human antibody (hCTMO1) in women with ovarian carcinoma. DESIGN: The monoclonal antibody labelled with Indium-111 was administered to women with suspected primary or recurrent ovarian carcinoma six days pre-operatively. The first group of women was given a dose of 0.1 mg per kg body weight of radiolabelled antibody. A second group of women received 1 mg per kg body weight and finally a third group was given 1 mg per kg body weight of unlabelled antibody followed one hour later by 0.1 mg per kg body weight of radiolabelled antibody. All the women were then imaged using a gamma camera one hour and up to 96 hours after injection. PARTICIPANTS: Fourty-four women in whom there was a high suspicion of primary ovarian carcinoma on the basis of ultrasound or CT imaging and serum CA125 and those in whom there was a suspicion of recurrent ovarian carcinoma after being treated for histologically confirmed carcinoma. SETTING: The Queen's Medical Centre, Nottingham and University Hospital Vrije Universiteit, Amsterdam, The Netherlands. RESULTS: At the low dose of antibody the sensitivity for detection of ovarian carcinoma was 70%. After increasing the dose of antibody and also after pre-dosing with unlabelled antibody the sensitivity increased to 100%, but there was a large number of false positive results at the higher dose, and therefore the specificity was low. The liver and bone marrow were the organs with the highest activities. CONCLUSION: The genetically engineered antibody hCTMO1 is safe for use in women. This antibody effectively targets ovarian carcinoma and has greater potential as a vector for therapeutic use than as a diagnostic agent.

Biodistribution of 111In-labelled engineered human antibody CTM01 (hCTM01) in ovarian cancer patients: influence of prior administration of unlabelled hCTM01.

mAb hCTM01 binds a carcinoma-associated antigen, the MUC1 gene product. The antigen is also present in the circulation, and administration of 111In-labelled hCTM01 results in the formation of immune complexes with enhanced accumulation in the liver. To avoid the unwanted effect of circulating radioactive immune complexes, a strategy to remove the circulating antigen was investigated using a split-dosage schedule. Eleven patients suspected of having ovarian carcinoma were injected with 1 mg/kg unlabelled hCTM01, 1 h before receiving 0.1 mg/kg 111In-labelled hCTM01 (100 M Bq). The amount of radioactivity was determined in resected tumour tissue, various normal tissues and blood samples obtained at laparotomy 6 days postinjection (p.i.). In all patients, the circulating antigen decreased to its nadir after the unlabelled antibody infusion and immune complex formation was demonstrated. Uptake in tumour deposits 6 days p.i. was 11.1 times higher than in normal tissues (P < 0.0001) and 5.9 times higher than in blood (P < 0.0001). 111In activity in liver tissue was comparable to 111In uptake in tumour tissue, and considerably lower than previously reported in patients not pretreated with unlabelled antibody. The split-dosing strategy would appear to be advantageous for use of hCTM01 as a specific carrier for the delivery of cytotoxic agents to patients with ovarian cancer.