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Biomedical subjects

H Kitchener

Publications and source records attributed to H Kitchener.

At least 19 recordsLinked to original sources

Management of endometrial cancer.

AIM: To review broadly the diagnosis and treatment of endometrial cancer, concentrating on the evidence base. METHODS: The peer reviewed literature has been cited selectively to support the principal themes of the review. RESULTS: A rising incidence of endometrial cancer will continue to present challenges to improve survival particularly for high-risk and advanced disease. Lymphadenectomy and adjuvant radiotherapy are and will be used more rationally as evidence for their effectiveness accumulates. CONCLUSIONS: The area of greatest need in endometrial cancer is now to improve outcomes for women with advanced/recurrent disease.

Combined Modality Therapy↗

Women's experiences of information, psychological distress and worry after treatment for gynaecological cancer.

Sensitive, appropriate patient information is considered to be an important element in the psychological support of patients. Specialist nurses are seen to have a key responsibility for this work. With regard to gynaecological cancer, evidence suggests that women do not get optimum psychological care. This study set out to explore women's experiences of information, psychological distress and worry after treatment for gynaecological cancer. The study was a survey (not an RCT) and 70 patients from two specialist gynaecological oncology centres were interviewed at the time of diagnosis/initial treatment and again at 6 months. The semi-structured schedule included recognised instruments to assess; sources of information, concerns, and psychological distress. Both initially and at 6 months there was evidence of a considerable burden of worry; over half the women had four or more significant concerns related to their illness experience. However, women who had initial support from a clinical nurse specialist at the time of diagnosis experienced a clinically significant reduction in their level of psychological distress 6 months from diagnosis. Hospital linked professional sources of information were well used at the time of diagnosis, but by 6 months many patients were using non-professional sources such as television, magazines and newspapers. This study suggests that support from a clinical nurse specialist may be able to assist psychological recovery. However, to be effective in this area nurses should be skilled and willing to assess the individual's need for help with information, and managing their worry.

Adaptation, Psychological↗

Levels of the DNA adduct, N7-methyldeoxyguanosine, are associated with increased risk of failure of treatment of cervical intraepithelial neoplasia.

OBJECTIVE: To determine whether exposure to methylating agents was a risk factor for treatment failure in women undergoing colposcopic examination. METHODS: Nine hundred fifty-eight women attending for colposcopic examination after abnormal cervical smear test results were recruited into the study cohort. Information on demographic factors, smoking and other risk factors was obtained and a pre-treatment biopsy was taken and stored at -70 degrees C. After follow-up, cases who had treatment failure of cervical intraepithelial neoplasia (CIN) within 2 years following treatment were identified (n = 77) and matched to women with no treatment failure of CIN in this time period (controls, n = 154). DNA was extracted from the pre-treatment biopsies and levels of N7-methyl-deoxyguanosine (N7-MedG), a marker of exposure to methylating agents, were quantified as the ring-opened form of the base damage by a validated immunoslotblot assay. RESULTS: Sufficient DNA for N7-MedG analysis was extracted from 61 subjects corresponding to 20 matched case control pairs. N7-MedG was detected in cervical DNA with levels ranging from non-detected (<0.1 micromol/mol dG) to 4.83 micromol/mol dG. N7-MedG levels were significantly higher in cases (geometric mean 0.99 micromol/mol dG) than controls (0.33 micromol/mol dG; P = 0.01). There were no associations between N7-MedG levels and HPV or smoking status. Log N7-MedG content, after adjustment for HPV status at time of treatment, was found to be significantly associated with increased risk of treatment failure (OR 5.74, 95% CI 1.05-31.23). CONCLUSIONS: The association between pre-treatment levels of DNA damage induced by methylating agents and subsequent treatment failure implicates methylating agent exposure as a causative factor in treatment failure.

Adult↗

Does improving communication and information for women increase attendance at colposcopy in an inner city clinic? A randomised controlled trial.

PURPOSE: To establish whether information leaflets and appointment reminders improve attendance for diagnostic colposcopy. DESIGN & SETTING: Randomised controlled trial in an inner city colposcopy clinic. PARTICIPANTS: 500 women newly referred to the colposcopy clinic with abnormal cervical screening smear results were randomly assigned to an intervention or control group using computer-generated numbers. INTERVENTION: 233 women referred for colpoposcopy were sent a comprehensive information leaflet with their appointment details and additionally were sent reminder letters regarding their appointment 7-10 days prior to their appointment date. CONTROL: 267 women were sent the standard basic information prior to their appointment. MAIN OUTCOME MEASURE: Attendance and default rates for diagnostic colposcopy. RESULTS: Default in the intervention arm was 42 out of 233 (18%) compared with 93 out of 267 (35%) in the control arm. CONCLUSION: Improved communication and information in the form of a detailed leaflet and a reminder letter for women with a recently abnormal smear result increased attendance for initial colposcopy assessment.

Adult↗

Management of women who test positive for high-risk types of human papillomavirus: the HART study.

BACKGROUND: Certain types of human papillomavirus (HPV) are the primary cause of almost all cervical cancers. HPV testing of cervical smears is more sensitive but less specific than cytology for detecting high-grade cervical intraepithelial neoplasia (CIN2+). HPV testing as a primary screening approach requires efficient management of HPV-positive women with negative or borderline cytology. We aimed to compare the detection rate and positive predictive values of HPV assay with cytology and to determine the best management strategy for HPV-positive women. METHODS: We did a multicentre screening study of 11085 women aged 30-60 years. Women with borderline cytology and women positive for high-risk HPV with negative cytology were randomised to immediate colposcopy or to surveillance by repeat HPV testing, cytology, and colposcopy at 12 months. FINDINGS: HPV testing was more sensitive than borderline or worse cytology (97.1% vs 76.6%, p=0.002) but less specific (93.3% vs 95.8%, p<0.0001) for detecting CIN2+. Of 825 randomised women, surveillance at 12 months was as effective as immediate colposcopy. In women positive for HPV at baseline, who had surveillance, 73 (45%) of 164 women with negative cytology and eight (35%) of 23 women with borderline cytology were HPV negative at 6-12 months. No CIN2+ was found in these women, nor in women with an initial negative HPV test with borderline (n=211) or mild (32) cytology. INTERPRETATION: HPV testing could be used for primary screening in women older than 30 years, with cytology used to triage HPV-positive women. HPV-positive women with normal or borderline cytology (about 6% of screened women) could be managed by repeat testing after 12 months. This approach could potentially improve detection rates of CIN2+ without increasing the colposcopy referral rate.

Adult↗

Collection devices for obtaining cervical cytology samples.

OBJECTIVES: The false-negative rate of cervical smears varies between 1.5% and 55%. This variation may be partly due to differences in sampling device and technique. The objective of this review was to assess different cervical sampling devices for collecting endocervical cells, which are thought to be a surrogate for detection of abnormal cells and adequate smear rates. SEARCH STRATEGY: We searched the Cochrane Gynaecological Cancer Group trials register and MEDLINE up to July 1997. We also handsearched 16 journals. SELECTION CRITERIA: Randomised and quasi-randomised trials and non-randomised comparative studies comparing cervical smear collection devices in women attending for primary screening, colposcopy following an abnormal smear or colposcopy after treatment. DATA COLLECTION AND ANALYSIS: Two reviewers independently abstracted data. Study quality was assessed. MAIN RESULTS: Thirty-four trials and six observational comparative studies were included. The Ayre spatula was shown to be less effective compared with extended tip spatulas for collecting endocervical cells in eight trials (odds ratio 2.25, 95% confidence interval 2.06 to 2.44). Use of a spatula with the cytobrush was more effective than spatula alone at collecting endocervical cells (odds ratio 3.33, 95% 3.05 to 3.63) and the same effect was present for adequate smear rates (odds ratio 1.51 95% 1.19-1.92). Extended tip spatulas were also superior for the detection of dyskaryosis in seven trials (odds ratio 1.21, 95% confidence interval 1.10 to 1.33). Based on data from two trials and three observational studies, smears that contained endocervical cells were more likely to detect dyskaryosis, particularly in severe disease. The proportion of smears with endocervical cells present increased with increasing severity of the disease. REVIEWER'S CONCLUSIONS: Extended tip spatulas of various designs appear to be better for collecting endocervical cells than the commonly used Ayre spatula. The most effective combination appears to be the cytobrush with an extended tip spatula. The rate of detection of endocervical cells appears to be a valid and convenient surrogate for the ability to detect dyskaryosis and for adequate smear rates. The ability of the extended tip spatula with the cytobrush compared with the extended tip spatula alone to detect disease, needs to be evaluated in a trial.

Female↗

Progestagens for endometrial cancer.

OBJECTIVES: Progestagen therapy following primary surgery for endometrial cancer has been advocated to reduce the risk of recurrence. The objective of this review was to assess the effect of adjuvant progestagen therapy in endometrial cancer. SEARCH STRATEGY: We searched the Cochrane Gynaecological Cancer Group trials register and MEDLINE up to May 1999. SELECTION CRITERIA: Randomised trials of progestagen therapy in women who have had surgery for endometrial cancer. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and two reviewers abstracted data independently. MAIN RESULTS: Six trials involving 4351 women were identified. Three trials included women with stage one disease only, whereas three included women with more advanced disease. Based on five trials, overall survival was not improved by adjuvant progestagen therapy (OR 1.05, 95% CI 0.88 to 1.24). Endometrial cancer deaths and relapse of disease appears to be reduced by progestagen therapy OR 0.88 95% CI (0.71-1.1) and 0. 81 95% CI (0.65-1.01) respectively. However, non-endometrial cancer related deaths were more common in women treated with progestagens OR 1.33 (1.02-1.73). REVIEWER'S CONCLUSIONS: Current evidence does not support the use of adjuvant progestagen therapy in the primary treatment of endometrial cancer.

17 alpha-Hydroxyprogesterone Caproate↗

Surgery for cervical intraepithelial neoplasia.

OBJECTIVES: Cervical intra-epithelial neoplasia is treated by local ablation or lower morbidity excision techniques. Choice of treatment depends on the severity of the disease. The objective of this review was to assess the effects of alternative surgical treatments for cervical intra-epithelial neoplasia. SEARCH STRATEGY: We searched the Cochrane Gynaecological Cancer Group trials register and MEDLINE up to July 1997. SELECTION CRITERIA: Randomised and quasi-randomised trials of alternative surgical treatments in women with cervical intra-epithelial neoplasia. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and two reviewers abstracted data independently. MAIN RESULTS: Twenty-three trials were included. Seven surgical techniques were tested in various comparisons. No significant difference in eradication of disease was shown, other than between laser ablation and loop excision. This was based on one trial where the quality of randomisation was doubtful. Large loop excision of the transformation zone appeared to provide the most reliable specimens for histology. Morbidity was lower than with laser conisation, although all five trials did not provide data for every outcome. There were not enough data to assess the effect on morbidity compared with laser ablation. REVIEWER'S CONCLUSIONS: The evidence suggests that there is no obviously superior surgical technique for treating cervical intra-epithelial neoplasia.

Conization↗

Interventions for preventing blood loss during the treatment of cervical intraepithelial neoplasia.

OBJECTIVES: Good surgical technique and other interventions can reduce immediate and long-term blood loss which is a common complication of surgery for cervical intra-epithelial neoplasia. The objective of this review was to assess the effect of interventions to reduce blood loss due to surgery for cervical intra-epithelial neoplasia. SEARCH STRATEGY: We searched the Cochrane Gynaecological Cancer Group trials register. SELECTION CRITERIA: Randomised and quasi-randomised trials of vasopressin, tranexamic acid, haemostatic sutures or Monsel's solution in women who have had surgery for intra-epithelial neoplasia. DATA COLLECTION AND ANALYSIS: Two reviewers independently abstracted data. MAIN RESULTS: Seven trials were included. Vasopressin had a beneficial effect on peri-operative bleeding. Prophylactic tranexamic acid reduced haemorrhage after knife and laser cone biopsy. Packing with Monsel's solution resulted in less peri-operative blood loss and secondary haemorrhages than routine suturing. Elective suturing also appeared to increase the risk of amenorrhoea and dysmenorrhoea. Vaginal packing increased satisfactory colposcopy rates at follow-up and reduced post-surgical stenosis. REVIEWER'S CONCLUSIONS: Bleeding associated with surgery of the cervix appears to be reduced by vasopressin, which is used under local rather than general anaesthetic. Tranexamic acid appears to be beneficial after knife and laser cone biopsy. There are not enough data to assess the effects on primary haemorrhage. There is some evidence that haemostatic suturing has an adverse effect on blood loss, cervical stenosis and satisfactory colposcopy.

Blood Loss, Surgical↗

Dendritic cells infected with recombinant fowlpox virus vectors are potent and long-acting stimulators of transgene-specific class I restricted T lymphocyte activity.

The identification of dendritic cells (DC) as the major antigen-presenting cell type of the immune system, combined with the development of procedures for their ex vivo culture, has opened possibilities for tumour immunotherapy based on the transfer of recombinant tumour antigens to DC. It is anticipated that the most effective type of response would be the stimulation of specific, MHC class I restricted cytotoxic T lymphocytes capable of recognising and destroying tumour cells. In order to make this approach possible, methods must be developed for the transfer of recombinant antigen to the DC in such a way that they will initiate an MHC class I restricted response. Here, we demonstrate that murine DC infected with a recombinant fowlpox virus (rFWPV) vector stimulate a powerful, MHC class I restricted response against a recombinant antigen. A rFWPV containing the OVA gene was constructed and used to infect the DC line DC2.4. The infected DC2.4 cells were found to stimulate the T-T cell hybridoma line RF33. 70, which responds specifically to the MHC class I restricted OVA peptide SIINFEKL. The stimulatory ability of the rFWPV-infected DC2.4 cells lasted for at least 72 h after infection and was eventually limited by proliferation of uninfected cells. By comparison, DC2.4 cells pulsed with synthetic SIINFEKL peptide stimulated RF33.70 well initially, but the stimulatory ability had declined to zero by 24 h after pulsing. FWPV infection of DC2.4 up-regulated MHC and costimulatory molecule expression. rFWPV was also found to infect both immature and mature human DC derived from cord blood CD34+ progenitors and express transgenes for up to 20 days after infection. We conclude that rFWPV shows promise as a vector for antigen gene transfer to DC in tumour immunotherapy protocols.

Animals↗

A study of treatment failures following large loop excision of the transformation zone for the treatment of cervical intraepithelial neoplasia.

OBJECTIVE: To examine the long term efficacy of large loop excision of the transformation zone (LLETZ) in the treatment of cervical intraepithelial neoplasia (CIN) and to evaluate the relative diagnostic merits of colposcopy and cytology in the follow up of these women. DESIGN: A retrospective examination of cytology, colposcopy and histology records of the first 1000 women treated with LLETZ in Aberdeen from 1989 to 1991. SETTING: Colposcopy Clinic Aberdeen Royal Infirmary, Grampian Region, Scotland. RESULTS: Nine hundred and seventy-seven women (97.7%) were seen for follow up at least once and 317 were followed for as long as four years. This comprises 2812 woman years of follow up. The incidence of recurrent CIN was 27/1000 woman years and the cumulative rate of recurrence at four years was 10.1 per 100 women. Twenty-eight of the 59 women (47%) with abnormal colposcopy and proven CIN had a concurrent smear that did not show dyskaryosis. CONCLUSIONS: LLETZ is an effective from of treatment for CIN. Colposcopy was useful in the follow up of these women and expedited the treatment of persistent disease. We recommend that any follow up protocol should include a colposcopic assessment and cytological follow up for at least four years following treatment. Further data are required to determine the risk of recurrence beyond this time.

Adolescent↗

Serial quantitation of HPV-16 in the smears of women with mild and moderate dyskaryosis.

The aim of this study was to examine the efficacy of semi-quantitative polymerase chain reaction (PCR) testing in cervical smears as an adjunct to cytological surveillance in a cohort of women with mild or moderate dyskaryosis. The study population comprised a group of 62 women who underwent twelve months of cytological and colposcopic surveillance as part of a larger randomised prospective study of women with mild and moderate dyskaryosis. Semi-quantitative PCR for HPV-16 DNA was carried out on the initial and twelve month study smears before a large loop excision of the transformation zone (LLETZ) was carried out. Smears from a control population which comprised 167 women without a history of abnormal cervical cytology who were attending family planning and general practitioner clinics for routine cervical smears were tested similarly. The presence of high or intermediate levels of HPV-16 DNA on both the initial and twelve month study smear was positively associated with the identification of cervical intraepithelial neoplasia (CIN) grades II or III in the LLETZ specimen (P = 0.01). While the combination of HPV-16 DNA testing with cytology on a repeat cervical smear improved the selection of women with underlying CIN II/III, there was still a false negative rate of 53%. Twenty-nine women had 'low risk' levels of HPV-16 DNA and mild dyskaryosis or less on both repeat smears indicating suitability for surveillance, but in fact 34% of them had CIN II/III. This study supports the finding reported previously of an association between high and intermediate levels of HPV-16 DNA and CIN II/III.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗