Cyclooxygenase-2 expression and prostaglandin E(2) synthesis are up-regulated in carcinomas of the cervix: a possible autocrine/paracrine regulation of neoplastic cell function via EP2/EP4 receptors.

The prevalence of cervical cancer in South African women is reported as being the highest in the world, occurring, on the average, in 60 of every 100,000 women. Cervical cancer is thus considered an important clinical problem in sub-Saharan AFRICA: Recent studies have suggested that epithelial tumors may be regulated by cyclooxygenase (COX) enzyme products. The purpose of this study was to determine whether cyclooxygenase-2 (COX-2) expression and PGE(2) synthesis are up-regulated in cervical cancers. Real-time quantitative RT-PCR and Western blot analysis confirmed COX-2 ribonucleic acid and protein expression in all cases of squamous cell carcinoma (n = 8) and adenocarcinoma (n = 2) investigated. In contrast, minimal expression of COX-2 was detected in histologically normal cervix (n = 5). Immunohistochemical analyses localized COX-2 expression and PGE(2) synthesis to neoplastic epithelial cells of all squamous cell (n = 10) and adenocarcinomas (n = 10) studied. Immunoreactive COX-2 and PGE(2) were also colocalized to endothelial cells lining the microvasculature. Minimal COX-2 and PGE(2) immunoreactivity were detected in normal cervix (n = 5). To establish whether PGE(2) has an autocrine/paracrine effect in cervical carcinomas, we investigated the expression of two subtypes of PGE(2) receptors, namely EP2 and EP4, by real-time quantitative RT-PCR. Expression of EP2 and EP4 receptors was significantly higher in carcinoma tissue (n = 8) than in histologically normal cervix (n = 5; P < 0.01). Finally, the functionality of the EP2/EP4 receptors was assessed by investigating cAMP generation after in vitro culture of cervical cancer biopsies and normal cervix in the presence or absence of 300 nmol/L PGE(2). cAMP production was detected in all carcinoma tissue after treatment with exogenous PGE(2) and was significantly higher in carcinoma tissue (n = 7) than in normal cervix (n = 5; P < 0.05). The fold induction of cAMP in response to PGE(2) was 51.1 +/- 12.3 in cervical carcinoma tissue compared with 5.8 +/- 2.74 in normal cervix. These results confirm that COX-2, EP2, and EP4 expression and PGE(2) synthesis are up-regulated in cervical cancer tissue and suggest that PGE(2) may regulate neoplastic cell function in cervical carcinoma in an autocrine/paracrine manner via the EP2/EP4 receptors.

The value of magnetic resonance imaging in patients with carcinoma of the cervix (a pilot study).

Magnetic resonance imaging (MRI) was performed in 11 patients with untreated squamous carcinoma of the cervix. The MRI stage and clinical stage were both compared with the surgical stage. MRI stage was only accurate in three of the 11 patients (27.3%) while the clinical stage was correct in eight of the 11 cases (72.7%). MRI assessment of parametrial and lymph-node involvement was difficult to interpret. These preliminary findings suggest that MRI is not, at present, a useful adjunct to staging in the evaluation of patients with carcinoma of the cervix.

The influence of initial residual disease on the outcome of second-look laparotomy in patients with carcinoma of the ovary.

Sixty four patients with epithelial ovarian cancer underwent second-look laparotomy. Influencing factors on the outcome of the second-look laparotomy were analysed. Both grade and stage appeared to have an effect on the outcome of the procedure. However, this effect appeared to be dependent on the amount of residual disease after primary surgery. The amount of residual disease appeared to be independently associated with the outcome of second-look laparotomy.

Penile human papillomavirus infection in consorts of women with genital human papillomavirus infection. A pilot study.

A study determined the incidence of human papillomavirus (HPV) on genitalia of male consorts of women with histologically proven genital HPV lesions to be 50%.

Endometrial cytology--the Endo-pap direct endometrial sampler.

A study was designed to assess the clinical characteristics and diagnostic cytological accuracy of an endometrial sampler, the Endo-pap (Monoject; Sherwood Medical, St Louis, Mo., USA), a disposable plastic curette. The Endo-pap was compared with the Accurette (Rolon, Watford, UK), another plastic endometrial sampler used for histological investigation. Microcolpohysteroscopy was also employed as part of the procedure. Fifty symptomatic patients, median age 50 years, were studied; the majority (55.6%) had been referred for postmenopausal bleeding. The Endo-pap yielded adequate specimens in 90% of patients compared with 82% with the Accurette. In 7 patients, endometrial carcinoma was correctly diagnosed with all three diagnostic methods and no false-positive diagnosis was made.

Repeat laparotomy in ovarian carcinoma after primary surgery.

Thirty-two patients with malignant ovarian disease were referred after primary surgery to the Gynaecological Oncology Unit of Groote Schuur Hospital, Cape Town. All 32 patients underwent a re-laparotomy with a view to accurate staging and possible cytoreductive surgery. On referral, 24 patients (75%) had stage I or II disease and the remaining 8 patients (25%) had stage III and IV disease. Twenty-seven patients (81%) had ovarian malignant disease of epithelial origin while the remaining 5 patients (19%) had ovarian disease of nonepithelial origin. Five (20.8%) of a total of 24 patients with stage I or II disease had their disease stage raised after repeat laparotomy. The overall success rate of cytoreductive surgery, i.e. less than 2 cm residual disease, was 58%.

Tumour marker CA125 levels in a variety of benign and malignant conditions.

The levels of tumour marker CA125 were established in 515 patients with a variety of benign and malignant conditions. With a specificity of 60.3% and an overall sensitivity for malignant tumours of 54% (extra-ovarian serous papillary carcinomas 100%), it is the most reliable tumour marker at present available for epithelial ovarian cancer and is of considerable value in the management of this condition when considered in conjunction with other clinical measurements.

The long-term effects of radiation therapy on patients with ovarian dysgerminoma.

A retrospective chart review and questionnaire study was undertaken to look at the long-term effects of radiation therapy in ovarian dysgerminoma patients. Forty-three patients and 55 controls responded to a questionnaire that detailed bowel, bladder, thyroid, menstrual, reproductive, sexual, and growth function. Statistically significant differences in the number of bowel movements were noticed when comparing patients with controls. The authors noticed no significant differences between cases and controls in bladder function. No thyroid disorders were attributable to mediastinal radiation therapy. Most patients with intact uteri bleed monthly on hormonal replacement. Three patients with a remaining ovary and uterus resumed menstrual function after substantial doses of abdominopelvic radiation therapy. No patients have conceived. The authors noticed a slight increase in dyspareunia in the treated group, but most patients were satisfied with their sexual function. One premenarchal patient exhibited a growth disorder.

Maternal phenylketonuria: comparison of two treated full term pregnancies.

This case report documents the fetal outcome of two full term pregnancies in a patient with phenylketonuria (PKU). She was treated with a low phenylalanine diet preceeding and during both pregnancies. During her first full term pregnancy she was not able to maintain the rigid diet, and this pregnancy resulted in the delivery of a growth-retarded, microcephalic boy. In her second pregnancy the patient maintained the diet until her delivery at full term. Maternal blood phenylalanine levels remained with two exceptions below 600 mumol/l throughout pregnancy and an infant of normal weight and head circumference was born.

DNA cytometry of pure dysgerminomas of the ovary.

The value of DNA cytometry for predicting the malignant potential of pure dysgerminomas of the ovary was investigated. Feulgen-thionin DNA image cytometry and propidium iodide DNA flow cytometry were performed in isolated nuclei from paraffin-embedded tissue of 25 dysgerminomas. Nineteen were in clinical stage Ia1, and six were in stage III (two in IIIa and four in IIIb). Eight patients showed recurrences during a 5-year follow-up period and one patient died of the disease. The DNA index (DI; the modal DNA value compared with that of normal cells) of the tumor cells was computed from the image and flow DNA histograms. Comparable DI values, ranging from 1.29 and 3.23, were found with both types of cytometry. No correlation was found with the clinical stage or the recurrence state. Furthermore, it was striking that, although values were found strongly deviating from the normal diploid content (DI = 1.0) suggesting an unfavorable prognosis, the survival rate was relatively high. It can be concluded that prediction of the clinical course of pure dysgerminomas by DNA cytometry does not seem feasible.

The natural history of carcinoma of the cervix in young women.

Invasive carcinoma of the cervix was treated in 1,522 patients over a 10-year period at Groote Schuur Hospital. Data for each patient included place of residence, pathological characteristics of the tumour, nodal spread, histological evidence of human papillomavirus (HPV) infection, disease stage, treatment type, treatment complications, site of recurrence and survival time. Patients aged under 35 years comprised 11.6% of the total patient group. A retrospective cohort study compared women aged under 35 years of age at the time of entry into the study and women aged 35 years or more. In all, 82 eligible young patients were compared with random sample of 82 eligible older patients. Contingency tables, life tables and proportional hazards analysis were used where appropriate. There was no significant difference across the two age groups in the incidence of non-squamous tumours, or in the grades of squamous tumours. Similarly there was no evidence of differences in lymph node involvement or HPV infection. Young patients appeared to enter the study at significantly earlier stages of the disease, and a greater proportion of them underwent surgical treatment (diff = 36.4% +/- 13.5%). In both groups treatment complications were less frequently observed after surgery than after radiotherapy. Sites of tumour recurrence were similar in both groups, and there was no apparent difference in survival times.