A retrospective clinical audit of cervical smears reported as 'glandular neoplasia'.

The aims of this study were to review the diagnostic pathway of women with smears reported as 'glandular neoplasia' and to outline the management, colposcopy findings, treatment and final histological diagnosis in these women. The design was a retrospective review. A total of 114 women were identified over a 5-year period from the cytology database at the Royal Liverpool University Hospital Cytology Department, whose hospital case notes were available for review. Methods included a review of the case notes for the demographic details, indication for smear, colposcopic findings, investigation and/or treatment procedures, histology, final diagnosis and current disease status. Of 114 smears reported as 'glandular neoplasia', 67 were reported as consistent with cervical glandular intra-epithelial neoplasia (CGIN), six with endocervical adenocarcinoma, 36 with endometrial adenocarcinoma and five with other glandular neoplastic abnormalities. The average age was 46.5 years. 79 (69.3%) smears were routine call/recall and 36 (30.7%) women were symptomatic. The positive predictive value (PPV) for a significant histological abnormality in the CGIN smear group was 80.6% (23.9% invasive carcinomas, 43.3% CGIN and 13.4% CIN) and the PPV of an 'endometrial adenocarcinoma' smear was 86.1%. Smears indicating glandular neoplasia are associated with a high probability of clinically significant lesions, the PPV of a CGIN smear being over 80%. Immediate referral for colposcopy and assessment by an experienced colposcopist is recommended.

Vulvar intraepithelial neoplasia: long term follow up of treated and untreated women.

OBJECTIVE: To investigate the long term outcome of patients with vulvar intraepithelial neoplasia. DESIGN: A retrospective study using information obtained from patient casenotes. SAMPLE: One hundred and thirty-three women with a primary diagnosis of vulvar intraepithelial neoplasia (VIN), identified during a 15-year period. RESULTS: The diagnosis of vulvar intraepithelial neoplasia increased throughout the study period. Human papilloma virus changes were noted in 104 patients (78%); these women were significantly younger than those without (P < or = 0.001). Nineteen (14%) were managed by observation or medical treatment and the remainder by surgical methods. Histological or symptomatic recurrence after surgical treatment occurred in 55 (48%). When disease recurred, it usually did so within four years of treatment. Recurrence was more common following laser vapourisation than after local excision (75% vs 40%; P < or = 0.01). Progression to invasive disease occurred in nine patients (7%), none of whom were in the group being observed. Four deaths occurred in this group, three from gynaecological malignancies of the lower genital tract. CONCLUSION: Patients with vulvar intraepithelial neoplasia require long term follow up, and the risk of invasion may be higher than previously thought. Surgical treatment when required should be by excisional rather than ablative methods in most instances. In selected cases it is also possible to safely manage patients by more conservative methods.

Vulvar intraepithelial neoplasia with superficially invasive carcinoma of the vulva.

OBJECTIVE: To investigate the long-term outcome of patients presenting with vulvar intraepithelial neoplasia (VIN) with superficially invasive carcinoma of the vulva (SICa). DESIGN: A retrospective study using information obtained from patient case notes. SAMPLE: Twenty-six women found at presentation to have VIN in association with superficially invasive carcinoma were identified during a 15-year period. RESULTS: Pruritus vulvae was the most frequent presenting symptom in 18 patients (69%). Sixteen women (61.5%) had multiple symptoms. Features noted at vulvar examination were variable and none were pathognomonic of either VIN or of superficial invasion. All patients had VIN 3 in association with a superficially invasive carcinoma. Histological changes associated with human papillomavirus were found in 19 (73%) women. Half had a co-existent or previous abnormality of the lower genital tract. Local excision was the most frequent initial treatment (n = 9 [35%]). Mean follow up time was 65 months (range 12-174). Disease persisted after primary treatment in five women (19%). Both histological recurrence (of either VIN or SICa) or symptomatic recurrence occurred in 10 patients (38%). All patients who experienced recurrence did so within 36 months of treatment. Overall, 12 patients (46%) relapsed (histological or symptomatic recurrence); the mean time was 18 months. Fourteen patients (54%) were managed satisfactorily by their initial treatment. One patient died of recurrent cervical cancer. Three progressed to frankly invasive disease: two (aged 31 and 39 years) with carcinoma of the vulva and one aged 34 years with carcinoma of the perianal margin. All are alive and well after treatment. One patient had recurrence of superficially invasive carcinoma treated by local excision with no further problems. No episode of metastasis via lymphatic or vascular channels has been seen. CONCLUSIONS: Patients with superficially invasive carcinoma of the vulva may be safely treated by local excisional methods without recourse to lymphadenectomy. Relapse after primary treatment is common, and there appears to be a significant risk of progression to frankly invasive carcinoma.

The prognostic significance of Bcl-2 and p53 expression in ovarian carcinoma.

Advanced ovarian cancer is characterized by poor prognosis and the development of resistance to chemotherapy. We have found that Bcl-2 and p53, two proteins implicated in the control of apoptosis, are differently expressed in the ovarian cell line A2780 and its cisplatin-resistant variant 2780CP, with the resistant line overexpressing both proteins. Transfection of the A2780 cells with a Bcl-2- or p53-expressing plasmid increases resistance to various drugs, including cisplatin, suggesting that Bcl-2 and p53 expression may influence the sensitivity of ovarian cancer cell lines to chemotherapy. Expression of these two proteins in vivo was determined by immunohistochemical staining of ovarian tumor biopsies from 70 patients. We found that Bcl-2 and p53 were expressed in 57 and 61% of specimens examined, respectively. Both p53 and Bcl-2 were found to be independent prognostic indicators of survival in ovarian cancer. Survival was poorer in patients with tumors expressing high levels of p53, whereas expression of Bcl-2 was associated with improved survival.

The influence of diltiazem and nifedipine on the haemodynamic and tubular responses of the rat kidney to renal nerve stimulation.

An investigation was undertaken in the pentobarbitone anaesthetized rat to determine the influence of calcium entry blockade on the haemodynamic and tubular responses of the kidney to renal sympathetic nerve stimulation. Electrical activation of the nerves, at rates causing a 12% reduction in renal blood flow, did not change glomerular filtration rate but significantly reduced urine flow (32%) and absolute (34%) and fractional sodium excretion (33%). Intravenous administration of diltiazem (10 and 20 micrograms/kg/min) and nifedipine (1.0 and 2.0 micrograms/kg/min) caused significant reductions of systemic blood pressure. Stimulation of the renal nerves, to reduce renal blood flow between 15% and 18% in the presence of both low and high doses of diltiazem, caused significant falls in glomerular filtration rate of 9% and 23%, respectively. During the low dose of nifedipine glomerular filtration rate did not change but in animals receiving the higher dose it fell by 17%. The magnitude of the neurally induced changes in urine flow, absolute and fractional sodium excretions were not different at either dose level of diltiazem or nifedipine from that observed in the absence of drugs. Stimulation of the renal nerves at low rates, which did not change renal blood flow, had no effect on glomerular filtration rate but significantly reduced urine flow (38%) and absolute (39%) and fractional sodium excretion (35%). At these low rates of nerve stimulation glomerular filtration rate remained unchanged during the infusion of either dose level of diltiazem. However, during administration of both the low and high doses of nifedipine there were significant reductions of glomerular filtration rate of 20% and 17%, respectively. The magnitude of the neurally induced changes in urine flow, absolute and fractional sodium excretions in the presence of both low and high doses of diltiazem and nifedipine were the same as those observed in the absence of drugs. The results of this study provide no evidence to indicate that the nerve mediated increases in tubular sodium reabsorption, a response involving alpha-adrenoreceptors, is dependent on the movement of calcium into the epithelial cells. The data did not indicate that blockade of calcium entry into cells impaired the ability of the kidney to regulate glomerular filtration rate which appeared to be due to a lack of renal efferent arteriolar vasoconstriction.