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Biomedical subjects

E J Buxton

Publications and source records attributed to E J Buxton.

At least 19 recordsLinked to original sources

Groin recurrence following Stage 1A squamous cell carcinoma of the vulva.

BACKGROUND: It has been well established that stage 1 squamous cell carcinomas of the vulva with a depth of stromal invasion less than 1 mm have a <1% risk of lymph node involvement. The treatment for these stage 1A tumours has therefore been to perform radical wide local excision without removal of groin nodes. CASE: We present two cases of stage 1A microinvasive cancer of the vulva that presented with groin recurrence 3 months and 3 years following their primary surgery respectively. CONCLUSION: The current management of stage 1A tumours may need to be re-evaluated to include some form of lymph node assessment in view of these rare but nonetheless aggressive tumours.

Carcinoma, Squamous Cell↗

Molecular detection of tumour DNA in serum and peritoneal fluid from ovarian cancer patients.

We have analysed DNA extracted from the serum and peritoneal fluid of 20 ovarian cancer patients for the presence of tumour-specific genetic alterations. The 20 patients included six with stage Ia disease. Using six polymorphic microsatellite loci we were able to detect novel alleles or loss of heterozygosity in 17/20 serum samples and 12/19 peritoneal fluid samples. Tumour-specific abnormalities were detected in the serum of all but one of the stage Ia cases. Half of the occurrences of loss of heterozygosity identified in primary tumour material were detectable in the serum samples. Novel alleles indicative of microsatellite instability were found in 3/6 patients with stage Ia disease but in only 1/14 of patients with more advanced disease. One of the eight patients in the control group displayed abnormalities in her serum DNA. The ease with which tumour-specific alterations were detected in serum and peritoneal samples from ovarian cancer patients, using a panel of only six polymorphic microsatellite markers on four chromosomes, suggests that molecular detection methods could prove useful in the staging, monitoring and screening of this disease.

Alleles↗

Digital imaging colposcopy, image analysis and quantification of the colposcopic image.

OBJECTIVE: To investigate the use of a digital imaging system for colposcopy, its use for image analysis and quantification of the colposcopic features that may predict histological outcome as defined by large loop excision of transformation zone. DESIGN: Prospective programme study of all patients undergoing colposcopy for cytological abnormalities. SETTING: Dudley Road Hospital, Birmingham. SUBJECTS: Fifty consecutive patients having cytological and colposcopic abnormality treated with large loop excision of transformation zone formed the study group. MAIN OUTCOME MEASURES: Pretreatment and colposcopic features correlated with histological diagnosis of excised transformation zone. RESULTS: Index cytology and current smoking status are the most important variables for prediction of histological diagnosis. Other important variables are focality of lesion, surface pattern, intercapillary distance and degree of acetowhiteness. CONCLUSION: Digital imaging colposcopy allows image capture, processing and objective analysis. This methodology holds advantages for basic and clinical research, teaching, diagnostics and clinical audit. The system can act as a quality control tool for colposcopy units. This system should prove invaluable for further quantitative studies, for natural history studies and for those patients with deferred treatment of their cytological and colposcopic abnormalities. The statistical models described may be incorporated into the system and can aid the colposcopist in management of the woman with abnormal cervical cytology and colposcopic abnormality.

Adolescent↗

A pilot study using 99mTc to measure lead and platinum in the human kidney.

A pilot study has been conducted to investigate the hypothesis that the chemotherapeutic drug, cisplatinum, can mobilize skeletal lead. In vivo measurements of lead and platinum in the kidney of chemotherapy patients were performed with the technique of x-ray fluorescence, using 99mTc in a backscatter geometry. The results of the pilot study were inconclusive; the majority of patients exhibited no evidence of kidney lead at the level of system sensitivity, and negligible blood and urine lead levels.

Cisplatin↗

Abnormal cervical cytology following large loop excision of the transformation zone: a case controlled study.

OBJECTIVES: To determine factors that may predict cytological outcome at 6 months following large loop excision of transformation zone (LLETZ) for cervical intra epithelial neoplasia (CIN) and to investigate the outcome in women with continuing cytological abnormality. DESIGN: Case controlled retrospective study. SETTING: Dudley Road Hospital, Birmingham and Midland Hospital for Women. SUBJECTS: Fifty-eight women with abnormal follow up cytology and a control group of 116 women. MAIN OUTCOME MEASURES: The relation between pretreatment and treatment factors and cytological outcome, and the relation between cytology and histology in women who had biopsies for persistent abnormal cytology. RESULTS: Univariate and stepwise logistic regression analysis showed that the number of sectors of atypical transformation zone (lesion size) and the excision margin status of the large loop excision specimen are of prognostic importance for the prediction of cytological abnormality at the 6 month follow up visit. Sixteen women have undergone further cervical biopsy. Of the five cases of persistent CIN, four had cytological changes showing moderate or severe dyskaryosis. Of the 11 women with koilocytosis or normal histology, 10 had mild dyskaryosis or borderline changes on their follow up cytology. CONCLUSION: Lesion size and excision margin status are important correlates of follow up cytology when treating patients for CIN with LLETZ. All women with abnormal cervical cytology at follow up should undergo colposcopic assessment. Excision biopsy is indicated if follow up cytology shows moderate or severe dyskaryosis, especially if still present 12 months after treatment.

Age Factors↗

Is stage I epithelial ovarian cancer overtreated both surgically and systemically? Results of a five-year cancer registry review.

OBJECTIVE: To review the incidence of Stage I epithelial ovarian carcinoma in the West Midlands region and to identify prognostic factors that have a significant effect on survival. DESIGN: A retrospective review of all Stage I ovarian cancer patients registered from 1.1.80 to 31.12.84. SETTING: West Midlands Regional Cancer Registry. POPULATION: 457 patients with Stage I ovarian cancer--373 with epithelial ovarian carcinoma. MAIN OUTCOME MEASURES: Survival at censor date of 30.6.89. RESULTS: 28% developed recurrent disease, and the overall 5-year survival of the group was 70%. Univariate analysis of all possible prognostic factors showed that stage, adjuvant chemotherapy, histological grade and type, surgical rupture of the tumour, intact capsule histologically, clinical finding of ascites and the performance of peritoneal washings were significantly associated with survival. Adequate surgical staging as defined by FIGO was not significantly associated with survival. A multivariate analysis based on the Cox proportional hazard model identified histological grade, adjuvant chemotherapy, patient age and peritoneal washings as having independent prognostic effects. Surprisingly adjuvant chemotherapy and peritoneal washings had negative effects on survival. CONCLUSIONS: Although a retrospective review has limitations, it would appear that adequate surgical staging and adjuvant chemotherapy confer no benefit in terms of survival in Stage I disease.

Adolescent↗

Experience with bleomycin, ifosfamide, and cisplatin in primary and recurrent cervical cancer.

The unfavorable prognosis for patients with advanced and bulky early stage cancer of the cervix may be improved by initial neoadjuvant cytoreductive chemotherapy. In a phase II study using ifosfamide in combination with cisplatin/bleomycin (BIP) in advanced and recurrent cervical cancer, we demonstrated a response rate of 69%. To determine whether this high response rate was a result of patient selection, and to assess the influence of combination chemotherapy on survival in patients with recurrent disease, a retrospective analysis of five phase II studies of bleomycin, ifosfamide, and cisplatin combinations was performed. The type of chemotherapy regimen (BIP v others) was the most significant factor in determining the likelihood of response. Combination chemotherapy did not appear to confer a survival advantage in patients with recurrent disease. The BIP regimen produced rapid responses with acceptable toxicity, and had potential for use as neoadjuvant therapy prior to radical radiotherapy in patients with advanced and bulky early stage disease. In an initial pilot study of this approach, 13 of 19 patients (68%) with primary inoperable disease had significant tumor regression prior to radical local radiotherapy. Interim analysis of the first 66 patients entered into a randomized study evaluating this approach has shown complete clinical tumor resolution after radical radiotherapy in 24 of 32 patients (75%) treated with up to three cycles of BIP prior to radiotherapy compared with 19 of 34 patients (56%) treated with radiotherapy alone. There has been no evidence that neoadjuvant chemotherapy enhances the acute toxic effects of pelvic radiotherapy. Therefore, this approach has potential to improve therapeutic outcome in patients with poor-prognosis primary disease.

Adult↗

The effect of ethnic origin on the rate of spontaneous late mid-trimester abortion.

The effect of ethnic origin on perinatal outcome is well recognized. An effect on the rate of spontaneous abortion has not been previously documented, to our knowledge. We report the results of a retrospective survey of late mid-trimester abortions (20 to 26 weeks gestation) at Dudley Road Hospital, Birmingham, England. The aims of the study were to document the rate of spontaneous late mid-trimester abortion by ethnic origin and to define any differences in these groups, both medically and as a result of histological examination of the abortus, that might account for observed differences. Over an 18-month period, during which 6508 infants beyond 26 weeks gestation were delivered, 30 late mid-trimester spontaneous abortions occurred (13 black, 10 white, 7 Asian). Abortion rates per 1000 deliveries were 12.9 for blacks, 3.6 for whites, and 2.7 for Asians. The differences between ethnic groups were statistically significant (chi 2 = 17.4; P = .0002). The black women experiencing spontaneous mid-trimester abortion were of higher mean parity and were more likely to have undergone a previous therapeutic termination. Review of pathology reports revealed more cases of chorioamnionitis and fetal pneumonia in this group. Although these results should be interpreted with caution, a relationship clearly exists between ethnic origin and late mid-trimester loss. Further study is warranted to establish the cause.

Abortion, Spontaneous↗

Out-patient peritoneal lavage cytology in the detection of residual epithelial ovarian cancer.

Peritoneal lavage fluid cytology was performed in 87 out-patients with histologically proven epithelial ovarian cancer undergoing primary management. A total of 246 peritoneal lavages were attempted, usually with temporary cannulae (n = 229). From these, 184 samples were obtained, of which 156 (85%) were suitable for cytological analysis. The sensitivity of peritoneal lavage fluid cytology in 67 patients with known residual disease was 57% whereas serum CA 125 levels were elevated in 58 (87%). Pre- and post-treatment peritoneal lavage fluid cytology had prognostic value, but this was less than that of serum CA 125 measurements.

Adult↗

Colposcopically directed punch biopsy: a potentially misleading investigation.

OBJECTIVE: To determine the relation between the histology of an initial colposcopically directed punch biopsy and a subsequent diathermy loop excision biopsy of the transformation zone, and the effect of lesion size on this relation. DESIGN: Prospective observational study of loop diathermy excision biopsies of the cervical transformation zone. SETTING: Academic unit colposcopy clinics at The Birmingham and Midland Hospital for Women and Dudley Road Hospital, Birmingham. SUBJECTS: 243 women managed by colposcopy and directed punch biopsy followed by loop diathermy excision. OUTCOME MEASURES: The histology of the punch biopsy and the excised transformation zone and the size of the abnormal lesion. RESULTS: In 132 (54%) of the 243 women the histology of the punch biopsy and loop excision specimen did not agree. In 62 (47%) of these 132 women a more severe lesion was found in the excised transformation zone, including three unsuspected adenocarcinoma in situ and one stage Ia1 cancer. In 39 (41%) of the 96 women in whom a lesion of CIN 3, or greater severity, was found in the loop excision specimen, the paired punch biopsy had suggested a lesion of lesser severity. In small area lesions, the punch biopsy was more likely to show more severe disease than the loop excision specimen (P = 0.0014). CONCLUSIONS: The results suggest that directed punch biopsy is an inadequate endpoint by which to judge the severity of an epithelial lesion. The findings have important implications for patient management and the design of trials and cast doubt on the results of studies using punch biopsy as an endpoint.

Biopsy↗

Loop diathermy excision of the cervical transformation zone in patients with abnormal cervical smears.

OBJECTIVE: To determine the efficacy and morbidity of fine loop diathermy excision of the cervical transformation zone as applied to the management of outpatients with abnormal cervical smears. DESIGN: Prospective programme trial with six month follow up. SETTING: Two hospital based colposcopy clinics. PATIENTS: 616 Patients aged 16-60 with abnormal cervical smears. INTERVENTIONS: After colposcopic and cytological assessment excision of the cervical transformation zone by fine loop diathermy under local anaesthesia in the outpatient department. MAIN OUTCOME MEASURES: Time to complete the treatment, immediate morbidity in terms of discomfort and bleeding, and cytological and colposcopic findings at six months. RESULTS: Treatment was completed in a mean of 3.47 minutes (SD 1.99). Immediate morbidity was minimal, and histological specimens were adequate in over 90% of cases. Almost two thirds of patients were treated at their first visit to the clinic. 58 Patients (9.4%) failed to attend for follow up at six months and one had had a hysterectomy. Of the 557 patients who attended for colposcopic and cytological follow up at six months, 506 (91%) were normal cytologically and 19 (3.4%) had histologically confirmed persistence of cervical intraepithelial neoplasia. The overall confirmed failure rate of the technique was 4.4%. CONCLUSION: Loop diathermy excision is an effective treatment with low morbidity and is an appropriate modality for patients with abnormal cervical smears.

Adolescent↗

A phase II study of ifosfamide in endometrial cancer.

Around 32% of all patients with endometrial carcinoma relapse after primary therapy. The outlook for these patients is poor. Ifosfamide (IFX) has activity in a number of gynaecological malignancies and was selected for evaluation in this disease. The aims of this study were to assess the activity and toxicity of IFX in recurrent endometrial carcinoma no longer amenable to radical local treatment. In all, 16 evaluable patients with symptomatic advanced metastatic or recurrent disease entered a phase II study of this drug. Patients received IFX (5 g/m2) as a 24-h infusion, with mesna (8 g/m2) given during and for 12 h following IFX to prevent urothelial toxicity. Treatment was repeated every 21 days. Two patients showed evidence of response [one complete response (CR) of 3 months and one partial response (PR) lasting 5 months]. Most patients experienced nausea and vomiting, and WHO grade 3/4 alopecia invariably occurred after two or more cycles. Four patients developed severe (grade 3/4) IFX/mesna CNS toxicity, and four other patients had mild (grade 1/2) CNS toxicity. Significant myelosuppression was seen in 3/41 cycles. Haematuria was uncommon and invariably mild. There were two toxic deaths (one due to grade 4 CNS toxicity and one due to septicaemia). IFX has activity in endometrial carcinoma, but responses are of limited duration and toxicity is considerable.

Adenocarcinoma↗

Phase II studies of ifosfamide alone and in combination in cancer of the cervix.

A series of phase II studies using ifosfamide (IFX) as a single agent and in combination with cisplatin and bleomycin (BIP) in advanced and recurrent cervical cancer have been coordinated at the West Midlands CRC Clinical Trials Unit (Birmingham, UK). The aims of these studies were to identify single agents and combination regimens that may be of value for palliation and have potential for use as neoadjuvant and adjuvant therapy at the time of primary treatment. A total of 79 patients with disease non-amenable to radical local therapy were treated with single-agent IFX or the BIP combination. In 30 patients treated with single-agent IFX, 10 objective responses (30%) were seen, with 1 complete response. In 49 patients treated with BIP, 34 objective responses (69%) were seen, with 10 complete responses (20%). Toxicity included alopecia, nausea and vomiting, myelosuppression, infection, reduction in renal function and disturbance of consciousness. These data indicate that IFX is highly active in cervix cancer and, in combination with bleomycin and cisplatin, can be used for effective palliation and cytoreduction in greater than 70% of patients. IFX-containing regimens have potential for use as neoadjuvant and adjuvant therapy in patients at high risk of recurrence with conventional treatment. These hypotheses are currently being tested in prospective randomised trials.

Adult↗

The potential for adjuvant therapy in early-stage cervical cancer.

Adjuvant therapy may potentially improve prognosis in women with early-stage cervical cancer who are at high risk of relapse after primary therapy. Patients with lymph node involvement at surgery are at high risk of recurrence and may benefit from adjuvant therapy, but many patients are treated with radical radiotherapy. At present there is no method of accurately identifying patients at high risk of recurrence in the latter group. A retrospective analysis of 141 surgically managed cases with stage I/II a cervical cancer is presented. The study aims were to characterize patients at high risk of relapse, identify independent prognostic variables predicting for relapse and, using these variables, develop a model, that would accurately predict high-risk patients. Univariate analysis identified depth of invasion, substage, lymph node involvement, lymphatic and blood vessel invasion and tumour differentiation as significant prognostic variables. After stratification for depth of invasion, which did not conform to the proportional hazards assumption implicit in the Cox model, Cox regression analysis showed substage, lymphatic and vascular invasion and histological tumour type to be independent prognostic variables. Using these variables, classification models were constructed that would be applicable to patients treated with either surgery or radiotherapy. Applying the models to 110 cases with greater than 18 months follow-up, 11/18 (61%) and 11/19 cases (58%) predicted as being at high risk of relapse have developed recurrence. Highly active chemotherapy is now available for this disease. We have demonstrated that combined bleomycin, ifosfamide and cisplatin (BIP) is one of the most active regimens in this disease. BIP produces cytoreduction in around 70% of patients with recurrent and primary advanced disease. Responses are achieved rapidly and acute radiotherapy toxicity is not enhanced by giving chemotherapy prior to radical local radiotherapy. A multicentre, prospective randomized trial testing the role of BIP as adjuvant therapy in patients with positive nodes at radical hysterectomy is now in progress. A complementary study testing the role of adjuvant chemotherapy in high-risk patients treated with radical radiotherapy is in preparation.

Adenocarcinoma↗