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Biomedical subjects

H C Kitchener

Publications and source records attributed to H C Kitchener.

85 records · Page 5Linked to original sources
PubMed1987

Colposcopy in a family planning clinic: a future model?

The first year's experience of a satellite colposcopy clinic in the Glasgow Family Planning Centre was analysed. Establishment of the clinic was supervised by an experienced member of the colposcopy team at the department of gynaecology, Western Infirmary, Glasgow, who trained one of the family planning centre's staff. Close links were thus maintained with the hospital clinic to which patients were referred for treatment. The policy at the new colposcopy clinic was to study prospectively all women in the hospital catchment area whose cervical smears were reported as abnormal. In 58 of 162 such patients there was at least moderate dyskaryosis and the cytologist's recommendation had been referral for colposcopy. In 104 cases the changes were either atypia alone or mild dyskaryosis and a repeat smear was recommended within three to 12 months; 18 of these patients had grade II or III cervical intraepithelial neoplasia on biopsy, and relying on repeat smears would have resulted in an 11.7% false negative rate. If an atypical cytological picture is to be an indication for colposcopy clinics attached to family planning centres may have an important role, given satisfactory training and close links with central specialist colposcopy clinics.

Biopsy↗
PubMed1986

Atypical condylomas of the cervix uteri in Singapore women: a histopathological and immunohistochemical study.

Subclinical flat cervical warts are commonly recognized by means of colposcopy. These warty lesions frequently contain cellular atypia of a varying degree showing all the features of cervical intraepithelial neoplasia (CIN) together with the features of wart virus infection e.g. koilocytosis. Human papillomavirus (HPV) antigens and DNA have been found in these lesions which can be called atypical condylomas. The presence of such markers in lesions regarded as having neoplastic potential implicates HPV in cervical carcinogenesis. We investigated a group of Chinese women in Singapore to see whether this hitherto unstudied group showed HPV markers, in particular, HPV antigens by means of the peroxidase-antiperoxidase (PAP) staining technique. We found that histological warty change and HPV antigens were commoner in early compared with advanced CIN. These results, which are similar to previous studies, suggest that the aetiology of cervical carcinoma is probably no different in Singapore than in the West. They also suggest that HPV infection of the cervix is endemic in non-Western countries as well as in the West and may play a role in cervical carcinogenesis in diverse racial groups.

Antigens, Neoplasm↗
PubMed1984

The presence of RNA complementary to HSV-2 (herpes simplex virus) DNA in cervical intraepithelial neoplasia after laser therapy.

In-situ hybridization of radiolabelled DNA probes to tissue sections detected RNA complementary to HSV-2 (herpes simplex virus) DNA in 65% (22 of 34) biopsies from cervical intraepithelial neoplasia (CIN) and in none of internally paired benign epithelia from individuals before treatment by laser vaporization cone. Laser therapy did not produce an increase in clinical or subclinical HSV infections of the cervix. Of 18 patients with RNA complementary to HSV-2 DNA in CIN biopsies before treatment, in whom treatment was successful, virus transcripts were detected at follow-up in only two of them.

Cervix Uteri↗
PubMed1983

Detection of herpes simplex virus type-2 DNA restriction fragments in human cervical carcinoma tissue.

DNA extracted from eight human cervical carcinomas, one lymph node metastasis and related control tissue was examined for the presence of herpes simplex virus (HSV) DNA sequences. Southern blot transfers of tumour and control DNA were hybridised with radioactively labelled cloned probes representing 70% of the HSV-2 genome. Specific hybridisation to HSV DNA sequences was observed in one of eight carcinoma tissues analysed. Hybridisation of HSV-2 DNA probes to BamHI and XhoI restriction enzyme fragments of tumour cell DNA which co-migrated with authentic HSV-2 viral fragments identified co-linear HSV-2 DNA sequences comprising 3% of the HSV-2 genome, between map coordinates 0.582 and 0.612. The remaining eight tumour and all control tissues analysed, showed no specific hybridisation to any of the probes used at levels of sensitivity which would detect 0.5 copies/cell of HSV-2 DNA restriction fragments of 2 kb or greater.

Base Sequence↗
PubMedDate not supplied

Age-restricted cervical screening: HPV testing at age 50 identifies a high risk group for cervical disease.

Changes to the present age policy of cervical screening are currently under consideration. We conducted a retrospective matched case-control study and cost analysis study to identify risk factors for the development of an abnormal smear after age 50 and to determine the impact of age-restricted cervical screening on the annual cost of the screening program. All women (229) from an 11-year birth cohort who developed an abnormal smear at age 50 or over were age-matched for two controls with negative smears. Routine screening smears taken between age 48 and 52 were tested for human papillomavirus (HPV) subtypes 16 and 18. Epidemiologic data were collected by postal questionnaire. Changes in costs under a policy of HPV testing and age-restricted screening were assessed. We found that HPV 16 status was the only independently significant risk factor for abnormal cytology after age 50 with an odds ratio of 10.26 (95% CI 1.25-84.11). A policy of early withdrawal from screening at age 50 on the basis of HPV testing would produce net cost savings. These findings suggest that HPV testing could be a valuable means of identifying the small proportion of women still at risk after 50, and of releasing health care resources.

Age Factors↗
PubMedDate not supplied

Clinical practice guidelines: loss of clinical freedom or a coming of age?

When a woman presents to us with gynecological cancer our duty is to offer the most effective means of treatment; that which maximizes the potential for cure at the same maintaining or improving quality of life. For the majority of our patients we are able to contemplate cure but for many, particularly those with advanced ovarian cancer, this will not be possible although we can provide the prospect of several years of survival. In an international context our ability to provide optimal care depends largely on the healthcare resources which are affordable, and although in many parts of the world these are very limited, the same principles apply. This series of articles will put the spotlight on effective care in gynaecological oncology following an evidence based theme. The articles will be informative, punchy and provocative. The first of these contributions looks at clinical guidelines: what are they for, how do we produce them and is there any evidence that they do any good?

Evidence-Based Medicine↗
PubMedDate not supplied

Assessing economics of treatments for gynecological cancer where clinical effectiveness meets value for money.

During the last 10 years, the management of gynecological cancer has been undergoing a great deal of change. This is due to a drive to reduce ineffective treatment and associated morbidity while at the same time maximizing the benefits of currently available treatment. The foundation for this approach has been high-quality clinical trials which have been performed in increasing numbers. These trials can provide strong evidence that treatments are equivalent or that a new drug adds superiority to previous treatment. The access that women have to the most effective forms of treatment often depends on the availability of healthcare resources and their affordability within the healthcare system. Healthcare decision makers increasingly require not just clinical effectiveness of treatments but also cost-effectiveness to be demonstrated. While health economic methods have been applied to many forms of cancer treatment and screening, there have been very few rigorous economic studies performed in gynecological cancer. This article discusses how economic analysis can be incorporated into clinical trials and how it can provide the sort of value for money determination that payers of healthcare are now requiring. Economic analysis may add a little to the cost of trials, but in the end, it may increase access to treatment by convincing decision makers of cost-effectiveness.

Clinical Trials as Topic↗
PubMedDate not supplied

Stage- and CA125-related survival in patients with epithelial ovarian cancer treated at a cancer center.

Current accepted prognostic indicators in ovarian cancer include performance status, surgical (FIGO) staging, and residual disease after operation. Here we present data from a prospective analysis of patients with ovarian cancer treated at the Christie Hospital. We confirm the independent prognostic effects of FIGO staging, performance status, and residual disease in our group of patients and furthermore show that CA125 levels at presentation to the oncology service are of independent prognostic significance (P= 0.02). We present survival data and show that the 3-year, cancer-specific survival for stage I disease is 90%. We postulate that this good survival may in part be due to the use of computed tomography scanning at presentation to allow accurate staging. Further clinical trials are needed to test whether combinations of surgical, histologic, biochemical, and radiologic parameters can be used to identify a population with such a good prognosis that adjuvant therapy is not required.

Adenocarcinoma↗
PubMedDate not supplied

Prime-boost vaccination strategy in women with high-grade, noncervical anogenital intraepithelial neoplasia: clinical results from a multicenter phase II trial.

The objective of this study was to determine the clinical effectiveness of a prime-boost human papillomavirus (HPV) vaccine regimen. A nonrandomized phase II prime-boost vaccine trial was conducted. Women with biopsy-proven anogenital intraepithelial neoplasia (AGIN) 3 were vaccinated with three doses of a recombinant fusion protein comprising HPV 16, E6/E7/L2 (TA-CIN) followed by one dose of a recombinant vaccinia virus encoding HPV 16 and 18 E6/E7 (TA-HPV). Clinical responses were evaluated by serial photographs, symptomatology, and biopsies before and after vaccination. Twenty-nine women were vaccinated; 27 with vulval intraepithelial neoplasia 3 and 2 with vaginal intraepithelial neoplasia grade 3. Clinical responses were seen in five women (17%), with one complete and five partial responses. Fifteen women (62%) had symptomatic improvement. No serious adverse effects were recorded. This is the first trial of a prime-boost vaccination regimen using heterologous HPV vaccines (TA-CIN followed by TA-HPV) in the management of AGIN. Since the prime-boost approach in this cohort offered no significant advantages over single TA-HPV vaccination, there are no further studies planned using this protocol. Future studies are warranted to define responders to immunotherapy.

Adult↗
PubMedDate not supplied

Pattern of failure and long-term morbidity in patients undergoing postoperative radiotherapy for cervical cancer.

The objective of this study was to assess treatment outcomes in a large case series of cervical cancer patients undergoing postoperative radiotherapy in a single center. Case notes of women referred to the Christie Hospital during 1985-1997 for postoperative adjuvant radiotherapy for cervical cancer were reviewed. Of 478 women eligible for analysis, 282 (58.9%) underwent radical hysterectomy and 196 (41.1%) had nonradical hysterectomy. The disease-specific 5-year survival for the study population is 70.1%, with a 5-year risk of developing any recurrence of 30.5% and a 5-year grade 3 morbidity rate of 3.9%. Survival was significantly higher, ie, 80.9% vs 62.7% (P = 0.0001) and recurrence was significantly lower, ie, 18.6% vs 38.8% (P < 0.00005) in the group of women who had adjuvant radiotherapy following a nonradical hysterectomy compared with radical surgery. Thirty percent of women having "radical" surgery had positive resection margins and required postoperative adjuvant pelvic radiotherapy. Women with node-positive disease, who received adjuvant radiotherapy, had a high rate of distant metastases. These women would receive chemoradiotherapy now as primary treatment because of the risk of developing distant metastases. If, despite staging investigations, surgery reveals node-positive disease, then these women should receive adjuvant chemoradiotherapy. Survival was better in women who had nonradical surgery due to smaller volume disease when cancers were unsuspected and hence will have been cured by surgery alone. Multidisciplinary team working, as recommended by national guidelines from 1999, should allow better patient selection for treatment.

Adenocarcinoma↗
PubMedDate not supplied

Spontaneous evolution of human papillomavirus infection in the uterine cervix.

BACKGROUND: Little is known about the natural history and the malignant potential of low-grade cervical intraepithelial neoplasia associated with human papillomavirus (HPV) infection. Cervical cancer remains the second most frequent cause of death in women across the world. Epidemiologic and molecular studies have shown that human papillomavirus (HPV) is associated with cervical carcinogenesis. In this prospective study we examined the behavior of low-grade cervical intraepithelial lesions associated with HPV infection over a 6-year period. MATERIAL AND METHODS: During 1992, women with Papanicolaou smears reporting koilocytotic atypia (HPV effect) with or without grade 1 cervical intraepithelial neoplasia (HPV +/- CINI, low grade squamous intraepithelial lesions, LgSIL), along with colposcopic impression of LgSIL were included to the study. Between 1992 and 1998 all women underwent repeat Papanicolaou smears, colposcopic evaluation and HPV DNA testing every six months. HPV typing of cervical scrapes was done by PCR. RESULTS: A total of 330 women completed at least 6 years of follow up. Among women with high-risk HPV types (16/18), the presence of dysplasia (grade 1 cervical intraepithelial neoplasia) was significantly correlated with the progression of the lesion; 29% of cases with HPV + CINI (15 out of 75) progressed to more severe lesions versus only 9% of cases with HPV infection (18 out of 225), P < 0.001, chi-square test. The incidence of histologically confirmed progressive lesions was significantly greater in women with mild dysplasia (18 out of 75, 24%) compared to women without dysplasia (13 out of 255, 5%), P < 0.001, chi-square test. CONCLUSIONS: In our study HPV typing was not predictive of the evolution of low-grade intraepithelial lesions associated with HPV infection. Standard cytologic screening and colposcopy are the most effective means of monitoring low-grade lesions.

Cervix Uteri↗