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D Luesley

Publications and source records attributed to D Luesley.

At least 19 recordsLinked to original sources
PubMed2003

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↗
PubMed2000

Phase II clinical trials of cisplatin-then-paclitaxel and paclitaxel-then-cisplatin in patients with previously untreated advanced epithelial ovarian cancer.

PURPOSE: To examine the activity and safety of two sequentially scheduled chemotherapy regimens comprising four cycles of paclitaxel (pctx) 200 mg/m2/3 hours then four cycles ofcisplatin (cisDDP) 100 mg/m2, and vice versa, in patients with previously untreated advanced ovarian cancer. PATIENTS AND METHODS: Between January 1994 and February 1996, we recruited 30 patients to the pctx-then-cisDDP regimen and 29 to cisDDP-then-pctx, in parallel phase II trials. RESULTS: Both regimens were predictably active with responses seen in 22 of 30 patients (OR 74%; CR 27%, PR 47%) treated with pctx-then-cisDDP, as against 13 of 21 patients (OR 62%; CR 38%, PR 24%) treated with cisDDP-then-pctx. The OR rate to four cycles of pctx (induction) was 43%, with 27% disease progression; the OR to four cycles of cisDDP (induction) was 57%, with 5% progression. However, progression rates across both induction and consolidation phases were 16% (pctx-then-cisDDP) and 29% (cisDDP-then-pctx). Both regimens were unacceptably neurotoxic. II patients suffering grade 3 sensory neurotoxicity (5 on pctx-then-cisDDP, 6 on cisDDP-then-pctx) and 20 having grade 3 deafness (9 on pctx- then-cisDDP, 11 on cisDDP-then-pctx). CONCLUSION: The activity of these sequential regimens justifies their further development using the less neurotoxic platinum analogue carboplatin, perhaps combining paclitaxel with other platinum non-cross resistant drugs.

Adult↗
PubMed2000

A randomised, prospective, phase III clinical trial of primary bleomycin, ifosfamide and cisplatin (BIP) chemotherapy followed by radiotherapy versus radiotherapy alone in inoperable cancer of the cervix.

BACKGROUND: Phase II studies have shown primary (neo-adjuvant) chemotherapy with bleomycin, ifosfamide and cisplatin (BIP) is active against inoperable cervical cancer. We present here results of a randomised phase III multicentre trial comparing radical radiotherapy with neo-adjuvant BIP chemotherapy followed by radical radiotherapy in patients with inoperable cervical cancer, designed to discover whether this combination might improve survival. PATIENTS AND METHODS: Patients with inoperable cervical carcinoma were randomised to pelvic radiotherapy alone [RT] or two to three cycles of bleomycin 30 units/24-hour infusion, ifosfamide 5 g/m2/24 hours, and cisplatin 50 mg/m2) chemotherapy followed by pelvic radiotherapy (BIP + RT). Randomisation was stratified by stage and radiotherapy centre. RESULTS: One hundred seventy-two eligible women were randomised into this trial; eighty-six to RT and eighty-six to BIP + RT. A total of 190 cycles of chemotherapy were given. Median follow-up for the 47 patients still alive is 9 years with a minimum follow-up of 3 years. Complete or partial response occurred in 51 of 86 (59%) of those randomised to RT and 60 of 86 (69%) of those randomised to BIP + RT. The difference between response rates does not reach statistical significance (chi2 = 2.06, P = 0.15). Median survival is two years with an actuarial survival at five years of 32% (95% confidence interval (95% CI): 25%-39%). There is no significant difference between the treatment groups (chi2log-rank = 0.11, P = 0.74). CONCLUSIONS: This study does not show any survival benefit from the use of neo-adjuvant BIP chemotherapy in advanced cervical cancer.

Adult↗
PubMed1999

Vulvar vestibulitis treated by modified vestibulectomy.

OBJECTIVE: A prospective study to evaluate the success of a modified vestibulectomy in treating vulvar vestibulitis. METHODS: Fifty seven consecutive women with vulvar vestibulitis and suitable for surgery based on the criteria: superficial dyspareunia, erythematous vestibular region, positive Q-tip test, symptoms reduced with local anesthetic cream. A modified vestibulectomy with or without a modified Fentons procedure was performed. Response was based on return to normal coitus, 3 months after surgery. RESULTS: Most women suffered from chronic conditions (median duration of symptoms = 18 months). The median age was 28 years (range 18-53). Any infections were treated prior to surgery. All but 4 (7%) had histological abnormalities, mainly non-specific inflammation. In 18% of women who had cervical cytology some abnormality was detected. Mean follow-up time was 12 months (range 2-42). Three women were not evaluable. Complete response to surgery was achieved in 33 (61.1%) of the women, partial response was achieved in 15 (27.8%). Six (11.1%) had persistent symptoms, four of whom has psychosexual problems. CONCLUSION: Presently, surgery remains the most successful intervention for vulvar vestibulitis. Modified surgery which is less destructive seems to afford acceptable results. The completion of randomized studies are needed to recognise the optimum surgical procedure.

Adult↗
PubMed1999

An audit of standards and quality in a teaching hospital colposcopy clinic.

The National Health Service Cervical Screening Programme has issued minimum standards for a colposcopy service that facilitates audit. We have looked at the performance of a teaching hospital colposcopy service by analysing the case notes of 639 women who underwent large loop excision of the transformation zone over a nine-month period in 1995. We found delays in patient assessment and communication of results. There was overtreatment, particularly at first visit, and an excessive number of treatments were performed under general anaesthesia. A worrying number of women failed to have a follow up smear performed, but in those that did we found a reassuring treatment success rate. Our findings led to changes in the structure and functioning of the colposcopy clinic that should improve the detection of significant disease and improve the timeliness of diagnosis and the speed with which we communicate results.

Colposcopy↗
PubMed1999

Serum and tissue antioxidant capacity in cervical intraepithelial neoplasia investigated using an enhanced chemiluminescent reaction.

Depleted antioxidant defence has been implicated in the pathogenesis of cervical neoplasia. We determined the systemic and local antioxidant status of women with this condition. Thirty-four women with varying grades of cervical intraepithelial neoplasia, 25 patients who had been treated successfully with diathermy loop excision, and 56 women who had no evidence of cervical abnormality acted as controls. Total antioxidant capacity of serum and protein-free serum, and of neat and protein-free homogenized cervical punch biopsies were determined using enhanced chemiluminescence. Mean serum antioxidant capacity of patients with current neoplasia and treated patients was not significantly different from that of controls. However, mean antioxidant capacity of homogenized cervical tissue from women with neoplasia was significantly lower than control means (P < 0.005), while results for treated patients were intermediate between those from diseased and normal samples (P < 0.05). The enhanced chemiluminescence technique has potential as a suitable method for measuring total antioxidant capacity of cervical tissue, and warrants further investigations using other tissue types. Significant antioxidant depletion in cervical intra-epithelial neoplasia appears to be confined to the local cervical mucosa.

Adult↗
PubMed1998

A pilot study on early post-operative morbidity and technique of inguinal node dissection in vulval carcinoma.

Inguinal lymphadenectomy is part of the management plan for most cases of vulval carcinoma. The surgical techniques have been modified over the years resulting in less destructive operations. Even so, inguinal lymphadenectomy continues to pose difficulties particularly relating to wound breakdown and lymphocyst formation. Many different methods are described, though none have undergone any comparative assessment regarding morbidity. This small study compares two methods performed on the same patients. The radical procedure included excision of the fascia lata and exposure of the femoral vessels and nerve. The anatomically-directed method was more conservative with surgery directed at removing the nodes as described in anatomical textbooks. Both methods resulted in equal lymph node retrieval, though the subjective short-term morbidity was reduced with the more conservative surgery. This approach did not result in any detrimental outcomes regarding relapse disease, though a randomised trial is required to corroborate these findings.

Carcinoma, Squamous Cell↗
PubMed1997

Community-based post-operative follow-up visit after major surgery for benign gynaecological conditions: a prospective study.

The time from surgery to discharge after major procedures for benign gynaecological conditions continues to fall. This small prospective study was undertaken to assess the postoperative problems encountered by patients after gynaecological surgery for a variety of benign disorders, and the potential of the 6-week surgical follow-up to be performed by the patient's family doctor rather than the hospital. The patients' and doctors' satisfaction with such care was determined. The study showed that follow-up in the community was acceptable to both patient and doctor. When problems arose after discharge most patients ( 50%) contacted their family doctor. At the 6-week visit few had physical problems, though most (58-100% depending on the Group) felt that a 6-week follow-up was required. Six-week postoperative follow-up by the family doctor is acceptable, and could permit more effective use of hospital specialists, though would increase the workload of family doctors.

Journal Article↗
PubMed1997

Sjögren's syndrome in women presenting with chronic dyspareunia.

OBJECTIVE: To identify cases of Sjögren's syndrome among women with chronic dyspareunia who did not already have a diagnosed rheumatological disorder. DESIGN: Prospective recruitment over 12 months. SETTING: Tertiary referral service for the assessment of vulval disease. PARTICIPANTS: Women with chronic dyspareunia who had musculoskeletal symptoms, Raynaud's phenomenon or symptoms of ocular or oral dryness. METHODS: The women underwent a Schirmer tear test and a comprehensive auto-antibody screen including latex fixation test for rheumatoid factor, antinuclear, anti-Ro, anti-La and anti-salivary duct antibodies. A labial salivary gland biopsy and vaginal biopsy were taken for routine histological analysis. MAIN OUTCOME MEASURES: Cases of definite and probable Sjögren's syndrome were identified using the European criteria. RESULTS: Eleven women were assessed for features of Sjögren's syndrome. Four had definite primary Sjögren's syndrome, two had probable primary Sjögren's syndrome and one had probable secondary Sjögren's syndrome. Among these seven women the median duration of vaginal symptoms was seven years (range 0.25-20), of ocular symptoms was one year (range 0.25-2) and of oral symptoms was 1.5 years (range 0-6). In all but one woman dyspareunia presented before ocular or oral symptoms, often by many years. CONCLUSIONS: Although well-recognised as a feature of established Sjögren's syndrome, this study emphasises that chronic dyspareunia can be a presenting feature in these women, antedating the emergence of ocular or oral symptoms by many years. Symptoms of ocular or oral dryness, Raynaud's phenomenon or musculoskeletal symptoms should be sought in women with chronic dyspareunia to identify those who merit further investigation.

Adult↗
PubMed1995

Long-term follow-up of patients with advanced ovarian cancer treated in randomised clinical trials.

The data from two prospective randomised phase III trials that were initiated by the West Midlands Ovarian Cancer Study Group (WMOCSG) in 1981 and 1986, recruiting 167 and 195 patients respectively, have been pooled and the survival patterns of the 362 patients treated for advanced epithelial ovarian cancer within clinical trials in the West Midlands over the 10 year period (1981-91) have been explored. All patients had histologically proven epithelial ovarian cancer and all had residual disease after primary surgery, with the majority having stage III/IV disease. The primary treatment for all patients was debulking surgery followed by platinum-based chemotherapy. Eligible patients were further randomised to undergo a second debulking operation. The main end point, survival, was assessed using Kaplan-Meier curves and the log-rank test. A Cox proportional hazards model identified performance status (P = 0.002), residual disease (P = 0.005) and albumin level (P = 0.04) as independent prognostic factors. A multivariate model to predict survival curves for patients with the best and worst prognoses was developed with predicted 5 year survival of 30% and 3% for those in the best and worst prognostic groups respectively. The identification of clinical interventions to improve outcome is an urgent matter since the prognosis for patients with advanced ovarian cancer remains poor.

Animals↗
PubMed1995

The application of flow cytometric DNA analysis in detecting the presence of malignant cells in ovarian carcinoma peritoneal fluids.

OBJECTIVE: To compare flow cytometric detection of malignant cells with standard cytological evaluation in patients with ovarian carcinoma. SETTING: The City Hospital Trust, The Women's Hospital and CRC Trials Unit, Birmingham. SUBJECTS: Forty-three patients with histologically proven ovarian carcinoma and positive cytology, and a control population of 20 patients undergoing surgery for benign gynaecological conditions. METHODS: Prospective, blinded study examining ascitic fluid or peritoneal washings obtained at primary surgery by flow cytometric DNA analysis and cytological examination. RESULTS: Flow cytometry detected aneuploid cells in 27/43 (63%) of malignant and 7/20 (35%) of benign fluid specimens. In malignant samples the mean aneuploid count was 38.5% (range 1-98%) with a mean S-phase fraction of 5.2% (range 0-33.9%). In benign specimens the mean aneuploid count was 30.4% (range 14.5-66.4%). Based on these results, the overall sensitivity of cytometric detection of malignant cells was 71.4%, specificity 65%, with a positive predictive value of 85.1%. False positivity was found mainly in patients with benign ovarian cysts. Further examination revealed four false negative and four false positive results, where the peritoneal fluid and ovarian tissue DNA ploidy status concurred. Assuming such results to be correct increased the sensitivity of the test to 88.5% and specificity to 85%. CONCLUSIONS: Although flow cytometry can glean information beyond the capabilities of cytological assessment, using the premise that aneuploid cells alone indicate malignancy, it remains secondary to cytology in the detection of malignant cells in peritoneal fluids.

Adult↗
PubMed1995

Prospective randomized trials on cytoreduction in ovarian cancer.

Ovarian cancer remains the main cause of death from gynaecological malignancy in England and Wales. Since the reports by Griffiths et al. in the 1970s that optimal cytoreduction to less than or equal to 1.5 cm is associated with an increase in survival there has been a gradual trend towards more radical surgery aimed at maximal tumour reduction. Since these first reports many others have made similar observations, so that now maximal surgical endeavour aimed at cytoreduction is almost standard practice. However, the majority of these reports are based on retrospective analysis, small numbers, poor standardization of treatment and other methodological inconsistencies. To date, no prospective randomized trials have been completed to confirm Griffiths's findings. The authors propose the case for a randomized trial before accepting a new and potentially morbid procedure as standard practice.

Female↗
PubMed1995

Pathology and management of vulval pain and pruritus.

Vulval pain and pruritus are symptoms associated with benign or malignant diseases. The paucity of information regarding aetiological factors confounds a logical approach to successful therapeutic and preventative strategies. Research continues to address the possible relationship between human papillomavirus and benign, premalignant and malignant vulval conditions. Although present in many conditions, oncogenesis caused by human papillomavirus has yet to be proven as a cause of vulvar premalignant and malignant diseases. The natural history and management of these and benign disorders have been reported during the period of review. Some of the new findings may alter present concepts and practices.

Female↗
PubMed1994

Cigarette smoking and histological outcome in women with mildly dyskaryotic cervical smears.

OBJECTIVE: To determine which patient related variables, available at the point of referral, predict the presence of high grade intraepithelial neoplasia when the smear result is mild dyskaryosis with or without co-existent koilocytosis. DESIGN: Multivariate analysis of prospective programme trial. SETTING: Academic Department Colposcopy clinics at Dudley Road Hospital, Birmingham, UK. SUBJECTS: One hundred and sixty-seven women, whose worst ever cervical smear was mild dyskaryosis with or without koilocytosis, referred to colposcopy clinics. All the women had complete data sets, as determined by the format of an ongoing programme, and all were treated by diathermy loop excision of the cervical transformation zone. MAIN OUTCOME MEASURES: Age, parity, contraceptive practice, smoking habit, duration of abnormal cytology and the grade of histology in the excised transformation zone. RESULTS: Forty-seven out of 78 (60%) smokers, compared with 18 out of 73 (25%) nonsmokers, had high grade disease. The other variables considered in the analysis were not significant or very weakly associated with histological grade when analysed in a univariate analysis. Stepwise logistic regression identified cigarette smoking as a powerful independent predictor of high grade disease. CONCLUSION: These data suggest a strong association between smoking and high grade intraepithelial neoplasia in a population of women whose worst ever smear report was mild dyskaryosis. Smoking is a variable that could be built into models to facilitate referral for colposcopic assessment.

Adolescent↗