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Biomedical subjects

W M Gregory

Publications and source records attributed to W M Gregory.

At least 37 records · Page 2Linked to original sources
PubMed1995

Burnout and psychiatric disorder among cancer clinicians.

The prevalence and causes of 'burnout' and psychiatric disorder among senior oncologists and palliative care specialists have been measured in a national questionnaire-based survey. All consultant non-surgical oncologists in the UK were asked to participate. Sources of work-related stress and satisfaction were measured using study-specific questions which were aggregated into factors. Psychiatric disorder was estimated using the 12-item General Health Questionnaire. The three components of 'burnout'--emotional exhaustion, depersonalisation and low personal accomplishment--were assessed using the Maslach Burnout Inventory. Three hundred and ninety-three out of 476 (83%) consultants returned their questionnaires. The estimated prevalence of psychiatric disorder in cancer clinicians was 28%, and this is similar to the rate among British junior house officers. The study group had equivalent levels of emotional exhaustion and low personal accomplishment to those found in American doctors and nurses, but lower levels of depersonalisation. Among cancer clinicians, 'burnout' was more prevalent among clinical oncologists than among medical oncologists and palliative care specialists. Psychiatric disorder was independently associated with the stress of feeling overloaded (P < 0.0001), dealing with treatment toxicity/errors (P < 0.004) and deriving little satisfaction from professional status/esteem (P = 0.002). 'Burnout' was also related to these factors, and in addition was associated with high stress and low satisfaction from dealing with patients, and with low satisfaction from having adequate resources (each at a level of P < or = 0.002). Clinicians who felt insufficiently trained in communication and management skills had significantly higher levels of distress than those who felt sufficiently trained. If 'burnout' and psychiatric disorder among cancer clinicians are to be reduced, increased resources will be required to lessen overload and to improve training in communication and management skills.

Adult↗
PubMed1995

The prognostic significance of DNA flow cytometry in breast cancer: results from 881 patients treated in a single centre.

In this single-centre study of 881 patients, S-phase fraction (SPF) was shown to be a significant prognostic marker in terms of overall survival (OS), relapse-free survival (RFS) and survival after relapse (SAR). Further, SPF had independent prognostic significance when considering a range of other clinicopathological variables, namely tumour grade and stage, nodal status, patient age, tumour size, menstrual status and treatment details. For OS and RFS, SPF was the second strongest predictor of the clinical course of the disease after nodal status, and for SAR it was the strongest prognostic marker. SPF correlated positively with histological grade but was the stronger predictor of survival. The distribution of SPF values was markedly different for the two ploidy classes of tumour, with DNA aneuploid tumours having a significantly higher average SPF. However, SPF retained its independent prognostic ability when DNA diploid and aneuploid tumours were analysed separately, DNA ploidy itself also proved to be an independent prognostic marker but the survival difference between the two ploidy classes was much less than that seen for different levels of SPF. Tumours with several DNA aneuploid populations (multiploid tumours) tended to have a worse prognosis than other aneuploid tumours but this trend did not reach statistical significance. In this and other studies from this centre, SPF has proved to be a robust predictor of clinical outcome in carcinoma of the breast.

Adult↗
PubMed1994

Serum progesterone at the time of surgery and survival in women with premenopausal operable breast cancer.

Serum progesterone and oestradiol levels have been measured in 210 premenopausal women with operable breast cancer on samples taken within 3 days of tumour excision. There was no relation between oestradiol level and time since last menstrual period, nor any effect of oestradiol value on prognosis. However, serum progesterone levels were related to the phase of the cycle as determined by time since last menstrual period. When divided on a basis of levels > 1.5 ng/ml (luteal phase) and < or = 1.5 ng/ml, it was found that there was no difference in survival between the two groups among 117 axillary node negative cases. However, in the 93 patients with positive axillary nodes, higher progesterone levels were associated with significantly better survival. Thus, serum progesterone levels at the time of surgery may affect the prognosis of premenopausal node positive patients with operable breast cancer.

Breast Neoplasms↗
PubMed1994

Acute corneal hydrops in keratoconus.

PURPOSE: To determine the clinical factors associated with the development of acute corneal hydrops and its subsequent outcome. METHODS: The authors identified 147 eyes (124 patients) with acute hydrops from a database of 5242 eyes (2723 patients) with keratoconus. They compared the clinical features of patients in whom hydrops developed with unaffected patients and assessed the progression to penetrating keratoplasty by actuarial methods. RESULTS: Patients in whom acute hydrops developed tended to be younger males who had advanced corneal ectasia and a poor corrected Snellen visual acuity at the diagnosis of their keratoconus (P < 0.001). Acute hydrops also was more common in the presence of severe allergic eye disease (P < 0.001). The development of hydrops was a very significant risk factor for subsequently receiving a penetrating keratoplasty (P < 0.00001) and at the end of the study period 87 (59%) of the 147 eyes had surgery for visual rehabilitation. These eyes had a greater rate of graft rejection than eyes grafted without hydrops (P = 0.02). After resolution of the hydrops, 46 of the 60 unoperated eyes had been refitted with contact lenses, of which 28 (61%) achieved a Snellen visual acuity of 20/40 or better, although a better visual acuity often was present in the contralateral eye. Microbial keratitis developed in two of these eyes after refitting. CONCLUSIONS: Although a penetrating keratoplasty often is indicated for visual rehabilitation after acute corneal hydrops, there is an increased rate of rejection. Only a minority of eyes were re-established in contact lenses after resolution of hydrops, but some patients achieved a functional level of visual acuity such that the procedure could be delayed or avoided.

Acute Disease↗
PubMed1994

Prognostic factors for the progression of keratoconus.

PURPOSE: The progression of keratoconus to a stage where penetrating keratoplasty (PK) is required for visual rehabilitation has considerable implications for affected patients. To assist with counselling, the authors have attempted to identify which factors measurable early in the course of the disease may indicate the likelihood of subsequent surgery. METHODS: The authors reviewed the records of all patients who attended a single center over a 7-year period for contact lens management of their keratoconus. The influence of clinical variables on the time taken for the worst eye to progress to PK was evaluated by actuarial methods and multivariate analysis. RESULTS: Included in the study were 2723 patients with a mean follow-up for unoperated eyes from the first visit of 4.5 years (range, 3 months to 28 years). Data were available for multivariate analysis in 2363 patients. At the end of the study period, 757 eyes (21.6% of all patients) had been grafted. The number of eyes progressing to PK was independently related to both the maximum and minimum keratometry, a corneal cylinder of more than 1.9 mm, the Snellen acuity, the racial group (P < 0.0001), and the age at presentation (P = 0.0006). Sex, laterality, systemic atopic disease, maternal or paternal age at birth, joint hypermobility, and a family history of keratoconus were not statistically related to outcome. Progression to PK in one eye increased the risk of progression in the contralateral eye (P < 0.0001) and a linear model of disease progression is proposed. CONCLUSIONS: Several clinical variables can be measured in patients at the presentation of keratoconus that influence the probability of a subsequent PK.

Adolescent↗
PubMed1994

A controlled trial of adjuvant tamoxifen, with or without prednisolone, in post-menopausal women with operable breast cancer.

A randomised clinical trial has been conducted to compare adjuvant tamoxifen, 20 mg daily, with tamoxifen and prednisolone, 7.5 mg daily, in post-menopausal women with operable breast cancer. There were 254 evaluable patients, of whom 128 were given tamoxifen alone and 126 received tamoxifen and prednisolone. After a median follow-up of 48 months there was no significant difference in relapse-free or overall survival of the two groups. Furthermore, with survival slightly favouring tamoxifen, confidence intervals on the hazard ratio established that a difference in favour of tamoxifen plus prednisolone of even 5% at 5 years was very unlikely (P < 0.02). Thus, despite the relatively small number of patients in this trial, the data clearly establish that prednisolone is not of value as an additional adjuvant agent.

Aged↗
PubMed1994

Expression of sialyl-Tn predicts the effect of adjuvant chemotherapy in node-positive breast cancer.

Sialyl-Tn (STn) is a carcinoma-associated carbohydrate determinant expressed on cancer-associated mucins and has the structure NANA alpha(2-6)alpha GalNAc. Expression of STn in colon and ovarian cancer is associated with a poor prognosis independent of tumour grade, stage or histological type. We have examined 237 cases of primary breast cancer for expression of this antigen using the antibody HB-STn (Dako). The frequency of STn expression was 31% in the whole group, 36% in the node-negative and 28% in the node-positive group. Survival was lower, but not significantly so, in the STn-positive group (P = 0.07), but this effect was highly significant for patients with node-positive disease (P < 0.002), the curves for node-negative disease being coincident (P = 0.31). In node-positive disease the effect was limited to those receiving adjuvant chemotherapy (P = 0.001). In a multivariate (Cox) analysis on the whole group STn staining, combined with adjuvant chemotherapy, showed a highly significant correlation with survival. In STn-negative cases, adjuvant chemotherapy improved survival (relative risk 2.3, 95% confidence intervals 1.4-3.9), whereas adjuvant chemotherapy did not influence survival in patients which expressed STn (relative risk 1.1, 95% confidence intervals 0.6-2.2). Thus, by either direct or indirect mechanisms, STn positivity appears to be a marker of resistance to adjuvant chemotherapy.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1994

Received dose-intensity: a randomized trial of weekly chemotherapy with and without granulocyte colony-stimulating factor in small-cell lung cancer.

PURPOSE: A prospective randomized trial to determine if granulocyte colony-stimulating factor (G-CSF) could increase the received dose-intensity (RDI) of weekly chemotherapy in patients with small-cell lung cancer (SCLC). PATIENTS AND METHODS: Forty patients with SCLC with good prognostic features (all patients with limited disease [LD], and extensive-disease [ED] patients with Eastern Cooperative Oncology Group [ECOG] 0 or 1 and plasma alkaline phosphatase levels < 1.5 times the upper limit of normal) were randomized to receive weekly chemotherapy with or without G-CSF. G-CSF (5 micrograms/kg) was self-administered subcutaneously on days when chemotherapy was not given. Chemotherapy consisted of cisplatin 50 mg/m2 intravenously (IV) on day 1 and etoposide 75 mg/m2 IV on days 1 and 2 alternating weekly with ifosfamide 2 g/m2 IV (with mesna) and doxorubicin 25 mg/m2 on day 1, for a total of 12 courses. Dose modifications (dose reductions and treatment delays) were made according to defined hematologic criteria. RESULTS: Dose reductions were made at some point during treatment in 12 of 17 patients in the control arm and in 11 of 23 patients in the G-CSF arm (P = .20). The proportion of patients experiencing dose reductions due to leukopenia was significantly higher in the control arm (nine of 17) compared with the G-CSF arm (four of 23, P < .04). Cycle delays due to leukopenia were similar in both arms of the study. The RDI was 82% of projected in the control arm (95% confidence interval [CI], 79% to 84%) and 84% in patients receiving G-CSF (95% CI, 82% to 87%) (P value not significant). CONCLUSION: In this randomized trial, G-CSF significantly decreased dose reductions due to neutropenia. However, administration of G-CSF did not decrease dose reductions or treatment delays to a level that would allow an increase in received dose-intensity. Nonhematologic toxicities such as increased creatinine concentration also prevented an increase in the RDI in the G-CSF arm.

Adult↗
PubMed1994

The classification of ductal carcinoma in situ and its association with biological markers.

One hundred five cases of pure ductal carcinoma in situ (DCIS) seen in the Guys Hospital breast unit between 1975 and 1991 were reviewed and reclassified using a modified histologic classification based on cytological features as well as histological architecture. The expression of p53 protein, cerbB2 protein, progesterone receptor, and a proliferation antigen KiS1, all factors reported to be of prognostic significance in invasive ductal carcinoma, was also evaluated using immunohistochemical methods. The mode of presentation of these cases was noted, and its relationship to biological markers and histologic type was also assessed. Good interobserver agreement was achieved by two independent observers using the modified histologic classification. Strong correlation was seen between histologic pattern and biological markers as well as between the individual markers. Poorly differentiated DCIS was associated with a high proliferation rate, the presence of cerbB2 and p53 protein and the absence of progesterone receptors. Well-differentiated DCIS showed the reverse, and the intermediate group showed an intermediate pattern. Paget's disease of the nipple was only seen in association with poorly differentiated DCIS, but no other significant association was noted between mode of presentation and DCIS type.

Adult↗
PubMed1993

Patient acceptability and practical implications of pharmacokinetic studies in patients with advanced cancer.

We have studied the practical implications and acceptability to patients of pharmacokinetic studies in 34 women receiving anthracyclines for advanced breast cancer. The following parameters were recorded: age, ECOG performance status, psychological state (Rotterdam Symptom Checklist), cytotoxic drug and dose, number of venepunctures for treatment and sampling, and time when the sampling cannula was removed. Immediately after finishing pharmacokinetic sampling, patients completed a questionnaire which revealed that (i) all patients understood sampling was for research, (ii) 35% of patients experienced problems with sampling, (iii) benefits from participation were perceived by 56% of patients. Of 20 patients later questioned after completion of their treatment course, 40% recalled difficulties with blood sampling. Factors identifying in advance those patients who tolerate pharmacokinetic studies poorly were not identified but the number of venepunctures should be minimised. Patients may also perceive benefits from 'non-therapeutic' research.

Adult↗
PubMed1993

Psychiatric disorder in patients with advanced breast cancer: prevalence and associated factors.

The prevalence of psychiatric disorder and associated factors has been examined in 139 women with advanced breast cancer. Patients completed a self-report assessment of mood, the Hospital Anxiety and Depression Scale (HAD). They were also interviewed to obtain sociodemographic details, UICC performance status and past psychiatric history. Overall, 35 (25%) scored 11 or above (out of a maximum of 21) on either the anxiety or the depression subscales, or both, of the HAD and were therefore probable cases of anxiety and/or depression. These patients are likely to benefit from psychosocial intervention. Clinical anxiety was unrelated to any sociodemographic or disease related factors. Clinical depression was significantly more prevalent amongst patients in the lower socioeconomic classes (P = 0.01) and those with poor performance status (P = 0.007). Depression can be difficult to detect in patients with advanced breast cancer and these factors may be useful indicators to clinicians of patients at high risk of this disorder.

Adult↗
PubMed1993

Advanced breast cancer: use of resources and cost implications.

Little information is currently available on the use of hospital resources and the resulting costs of treating any advanced cancer. Such data may be useful for planning purposes and for calculating the cost effectiveness of measures designed to reduce the incidence of advanced disease (such as the National Breast Screening Programme). A retrospective analysis of the medical records of 50 patients with advanced breast cancer who attended the Guy's Hospital Oncology Unit and who died between October 1988 and December 1990 has therefore been undertaken. For each patient, the duration of in-patient stays and principal indications for admissions were recorded, together with the number of out-patient attendances. Details of endocrine treatment, chemotherapy and radiotherapy were abstracted as were all radiological and laboratory investigations. Costs for each of these activities were calculated. The median duration of advanced disease was 17 months (mean 27 months; range 7 days-12 years). The mean cost of treatment per patients was calculated to be 7,620 pounds (range 317 pounds-27,860 pounds). Mean duration of in-patient stay was 32 days (0-133) and this accounted for 56% of total costs. The large majority (> 80%) of the time spent as an in-patient was for the care of serious illness rather than for specific antitumour treatment. Cytotoxic drugs accounted for 9% of the total cost, compared with 8% for radiotherapy and 13% for laboratory and radiological investigations.

Adult↗
PubMed1993

Spinal cord compression in breast cancer: a review of 70 cases.

Spinal cord compression (SCC) is a relatively uncommon but frequently disabling complication of metastatic breast cancer. We have conducted this retrospective study of 70 patients with SCC secondary to breast cancer with the aims of determining risk factors for its development and predictors of outcome. Median age at diagnosis of breast cancer was 51 years with median time to SCC 42 months. All patients had radiological evidence of bone metastases at the time of SCC, and only five were not known to have bone metastases prior to SCC. The most frequent symptom of SCC was motor weakness (96%) followed by pain (94%), sensory disturbance (79%) and sphincter disturbance (61%). Ninety-one percent of patients had at least one symptom for more than a week. Radiotherapy (RT) was given as primary treatment in 43 cases, whilst 21 had decompressive surgery and seven of these went onto have postoperative radiotherapy. Six patients were deemed too unwell for either modality. Following treatment, 96% of those who were ambulant before therapy maintained the ability to walk. In those unable to walk, 45% regained ambulation, with RT and surgery being equally effective. Median survival following SCC was 4 months, with no significant difference between those treated by RT or surgery. The most important predictor of survival was ability to walk after treatment, followed by time from diagnosis of breast cancer to SCC. We conclude that the majority of patients have warning symptoms of SCC and that nearly all will have evidence of spinal bone metastases before compression occurs. The results suggest that earlier diagnosis and intervention could improve outcome. There was no evidence of benefit from surgery over radiotherapy as primary treatment, survival in both treatment groups being poor.

Adult↗
PubMed1993

Chemotherapy of advanced breast cancer: outcome and prognostic factors.

The outcome for 758 consecutive patients who had received one or more chemotherapy regimens for recurrent or metastatic breast cancer is presented. The response rate following first line treatment was 34%. Median duration of response was 7.8 months, median time to progression was 3.7 months and median survival was 7.9 months. The only factor predicting for response, of factors recorded at presentation and at initiation of chemotherapy, was the use of anthracycline based regimens, though this may reflect the patient selection policy. Initial disease free interval, presence of liver metastases and use of anthracyclines were significantly related to time to progression. Several factors related to survival following first chemotherapy, but anthracycline usage showed only a very weak correlation. One third of patients (249/758) received two or more chemotherapy regimens. The response rate (16%) and median time to progression (2.3 months) were significantly worse than for first line treatment. The outcome after third line chemotherapy was very similar to that observed following second line treatment. Achievement of an objective response with first line chemotherapy predicted for second response, but with insufficient power to be of use in selecting patients for subsequent chemotherapy. Time to progression following first line chemotherapy did not influence that after second line treatment.

Adult↗
PubMed1993

A randomized trial comparing single-agent carboplatin with carboplatin followed by radiotherapy for advanced ovarian cancer: a North Thames Ovary Group study.

PURPOSE: To determine in a randomized trial of advanced ovarian carcinoma whether consolidation therapy with whole-abdominal radiotherapy (RT) after chemotherapy improves survival and disease-free survival compared with the continued chemotherapy. PATIENTS AND METHODS: Two hundred fifty-four patients with advanced epithelial ovarian cancer (stages IIB to IV) were entered onto a study of five monthly courses of 400 mg/m2 of carboplatin. One hundred seventeen patients with residual disease of 2 cm or less at second-look laparotomy or laparoscopy were then randomized to receive consolidation therapy, either five further courses of carboplatin at the same dosage or whole-abdominal RT (24 Gy). There was no control arm. RESULTS: Chemotherapy was well tolerated and was usually administered on an outpatient basis. Myelosuppression that was sufficient to delay chemotherapy occurred in only 3% of 1,418 courses analyzed. The main toxicity of carboplatin was nausea and vomiting, but this was easier to control than that with cisplatin. Although RT was well tolerated in the majority of the 58 patients, one patient who had been found to have multiple adhesions at second-look surgery developed fecal fistulae post-RT that resulted in the patient's death from peritonitis. Median survival for the whole group from date of surgery was 25 months. No statistical difference was found in either survival or disease-free survival between those patients who received consolidation chemotherapy and those who were treated with abdominal RT. Prognostic factors used to assess survival were stage, histology, amount of residual disease after primary surgery, and presence of tumor at second-look surgery. CONCLUSION: There seems to be no significant advantage for consolidation whole-abdominal RT compared with the continuation of the same chemotherapy in the management of advanced epithelial carcinoma of the ovary, even when no macroscopic residual disease is apparent at second-look surgery.

Adolescent↗