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Biomedical subjects

S D Heys

Publications and source records attributed to S D Heys.

At least 55 records · Page 3Linked to original sources
PubMed1998

Treatment of large and locally advanced breast cancers using neoadjuvant chemotherapy.

BACKGROUND: Neoadjuvant (primary) chemotherapy is being used increasingly in the treatment of patients with large and locally advanced breast cancer with the aim of reducing the size of the primary tumor and eliminating micrometastatic disease. Response rates to, compliance with, and survival of patients following neoadjuvant chemotherapy have been variable. We report the results of a consecutive series of 77 patients with breast cancer who received neoadjuvant chemotherapy. METHODS: Seventy-seven patients with locally advanced breast cancers were treated with multimodality therapy comprising up to six cycles of chemotherapy (cyclophosphamide, vincristine, doxorubicin, and prednisolone), radiotherapy, and then surgery. The median follow-up was 54 months. Clinical response rates to therapy and overall survival have been documented. In addition, prognostic factors for survival were identified using the Cox proportional hazards model. RESULTS: The overall objective response rate of the primary tumor to chemotherapy alone was 87% (25% complete and 62% partial responses, UICC criteria). Following radiotherapy the response rate was 90% (52% complete and 38% partial responses). The overall 5-year survival for all patients was 0.48. However, the probability of survival at 5 years was 0.74 in those with a complete response, and 0.36 if there was a partial clinical response, but no patients who had either stasis of disease or progression survived for 5 years. Independent predictors of better survival that were identified were a complete histopathological response after chemotherapy and radiotherapy, a complete clinical response to chemotherapy, and five or six cycles of chemotherapy versus four or less. CONCLUSIONS: Neoadjuvant chemotherapy in patients with large and locally advanced breast cancers can result in satisfactory local control and overall survival rates, especially in patients with a complete clinical or histopathological response after treatment.

Adult↗
PubMed1998

Gamma emission imaging in the management of breast disorders.

Breast cancer is the commonest malignancy to affect women. The malignant process may present clinicians with problems in establishing the diagnosis expeditiously, accurately staging the disease and assessing tumour response to primary systemic chemotherapy. Considerable recent interest has focused on the application of imaging techniques that utilize tumour-specific gamma-ray-emitting radiopharmaceuticals to resolve these problems. The wide availability of gamma camera systems makes single photon-imaging techniques, using radiopharmaceuticals incorporating conventional isotopes, attractive options. However, results concerning the detection of the primary breast cancer and the staging of axillary lymph nodes suggest that these techniques would appear to offer no significant advantages, when compared with those obtained using standard diagnostic methods. Dual gamma-ray-emission imaging by positron emission tomography (PET) may offer an alternative solution. Studies performed show that PET can accurately detect primary breast cancers, stage locoregional lymph nodes and visualize distant tumour metastases. Furthermore, PET may be able to monitor early tumour response to chemotherapy agents. It would appear, therefore, that dual gamma emission might have an important role to play in the management of patients with breast cancer.

Bone Neoplasms↗
PubMed1998

Hypercalcaemia in patients with cancer: aetiology and treatment.

Hypercalcaemia is one of the most common disorders occurring in patients with cancer and may have disabling symptoms. The mechanisms underlying hypercalcaemia associated with malignant disease, the symptoms attributable to and the treatment of this disorder are discussed in this paper.

Humans↗
PubMed1998

Psychosocial aspects of cancer in the elderly.

A number of studies have shown that older people are less distressed by the diagnosis of cancer than their younger counterparts. This may be because older people have fewer dependants and they are less likely to suffer financial difficulties and to experience disruption to their daily routine following the diagnosis. It is surprising, therefore, that many elderly patients do not receive the biologically optimal treatment of their disease, even when comorbid medical conditions are taken into account. This appears to reflect an age bias amongst professionals involved in the management of cancer. There is a paucity of studies examining the perspective of elderly patients themselves regarding factors they consider important in their management. Elderly patients with cancer are not an homogeneous group in terms of their views about management. The vast majority of elderly patients, in common with younger patients, consider that giving the most effective treatment for breast cancer is just as important for older patients as it is for younger patients and that, in making a decision about the best treatment for them, the surgeon should only take account of the biological aspects of the disease. Clinicians, therefore, should avoid making assumptions about what patients wish simply on the basis of the age of the patient. Although there is a recent trend towards more elderly patients participating in oncology treatment trials, there is a great dearth of information about the acceptability and effectiveness of psychosocial interventions in elderly patients.

Adaptation, Psychological↗
PubMed1998

The management of cancer of the breast in the elderly.

Breast cancer in older women continues to be a clinical problem and therapeutic challenge. The clinical presentation, biological characteristics and survival rates are comparable between older and younger women with breast cancer. Treatment of breast cancer in older women should aim to ensure satisfactory control of locoregional disease and prolongation of survival, for as long a period as possible. Optimal surgical therapy should be as for younger patients and adjuvant therapies may be required (considering side-effects and benefits). However, randomized trials are required to clarify the role of adjuvant treatments in older patients.

Adult↗
PubMed1998

Staging of the axilla in breast cancer: accurate in vivo assessment using positron emission tomography with 2-(fluorine-18)-fluoro-2-deoxy-D-glucose.

OBJECTIVE: To evaluate the ability of positron emission tomography (PET) with 18F-fluoro-2-deoxy-D-glucose (18F-FDG) to determine noninvasively axillary lymph node status in patients with breast cancer. BACKGROUND: The presence of axillary lymph node metastasis is the most important prognostic factor in women with breast cancer. It signifies the presence of occult metastatic disease and indicates the need for adjuvant therapy. The only reliable way in which this important prognostic information may be obtained is by performing axillary dissection, which may be associated with significant complications and delay in discharge from the hospital. PET with 18F-FDG can visualize primary cancers in the breast and metastatic tumor deposits. METHODS: Fifty patients with untreated breast cancer had clinical examination of their axilla performed (graded as positive or negative), followed by PET of the axilla and midthorax. PET data were analyzed blindly and graded as positive or negative, depending on the presence or absence of axillary nodal metastases. Cytopathologic assessment of the axillary nodes was carried out within 1 week of PET, by fine-needle aspiration cytology in 5 patients and axillary dissection in 45; the excised specimens were examined by a single pathologist. RESULTS: The overall sensitivity of PET in 50 patients was 90% and the specificity was 97%. Clinical examination of the same patients had an overall sensitivity of 57% and a specificity of 90%. In the 24 patients with locally advanced breast cancer (T3, T4, TxN2), PET had a sensitivity of 93% and a specificity of 100%. In T1 tumors (seven patients), the sensitivity and specificity were 100%. PET had a high predictive value (>90%) and accuracy (94%) in staging the axilla. CONCLUSIONS: PET is a sensitive and specific method of staging the axilla in patients with breast cancer. It may obviate the need for axillary surgery in women with small primary tumors, define the women likely to benefit from axillary dissection, or allow radiotherapy to be substituted for surgery, particularly in post-menopausal women.

Adult↗
PubMed1998

Distal procto-colitis, natural cytotoxicity, and essential fatty acids.

OBJECTIVES: Recently, it has been postulated that patients with ulcerative colitis have altered natural cytotoxicity, in particular natural killer (NK) and lymphokine-activated killer (LAK) cell activities. These cellular mechanisms have been postulated to play an etiological role in the pathogenesis of the disease process. We have shown previously that the essential fatty acids (EFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) specifically inhibit natural cytotoxicity. Our aim was to evaluate the role of omega-3 EFA in the modulation of natural cytotoxicity and disease activity in patients with distal procto-colitis. METHODS: In this pilot study patients were randomized into two groups. Each patient received either fish oil extract (EPA, 3.2 g, and DHA, 2.4 g) (n = 9) or sunflower oil (placebo) (n = 9) daily in a double-blind manner for 6 months. Monthly assessments of disease activity (clinical and sigmoidoscopic scores) and histological evaluation of mucosal biopsies were carried out. Also, the circulating levels and activities of NK and LAK cells, using flow cytometric analysis (CD16+ CD56+) and in vitro 51 chromium release assays (K562), respectively, were monitored. RESULTS: After 6 months' supplementation with EFA, there was improvement in the clinical activity compared with pretreatment evaluation. There was significant reduction in the sigmoidoscopic and histological scores in the EFA group compared with the placebo group. Essential fatty acid supplementation for 6 months also induced significant reduction in the circulating numbers of CD16+ and CD56+ cells and the cytotoxic activity of NK cells, compared with the placebo group. CONCLUSIONS: This pilot study has demonstrated that omega-3 fatty acids can suppress natural cytotoxicity and reduce disease activity in patients with distal procto-colitis. These findings suggest a therapeutic strategy for managing patients with inflammatory bowel disease.

Adult↗
PubMed1998

Potentiation of the response to chemotherapy in patients with breast cancer by dietary supplementation with L-arginine: results of a randomised controlled trial.

Patients with large primary breast cancers are being treated with neo-adjuvant chemotherapy. Studies in animals have shown that responses to chemotherapy can be increased by dietary manipulation of tumour cell metabolism. Also dietary supplementation with the amino acid L-arginine, resulted in an increase in tumour metabolic activity expression of the nuclear activation antigen, Ki67, in patients with breast cancer. Therefore, we have carried out a randomised, double blind, placebo controlled trial to determine if L-arginine supplementation is beneficial in patients with breast cancer, undergoing neo-adjuvant chemotherapy. 96 patients were randomised to receive L-arginine (30 g/day) for three days (n = 48) or placebo (n = 48) prior to undergoing chemotherapy (doxorubicin, cyclophosphamide, vincristine, prednisolone), 6 pulses at 21-day intervals. Clinical and pathological responses were assessed in both groups of patients following completion of chemotherapy. The clinical response rate was 77% (23% complete and 54% partial responses) in the L-arginine treated group, compared with 71% (15% complete and 56% partial) in the placebo group of patients (p = ns). However, in patients with tumours less than 6 cm in initial diameter, there was a significant increase in the better histopathological responses in the L-arginine group, when compared with the placebo group of patients (88% vs 52%, p = 0.04). This may have important implications for clinical practice.

Adenocarcinoma↗
PubMed1998

Acute phase proteins in patients with large and locally advanced breast cancer treated with neo-adjuvant chemotherapy: response and survival.

Seventy-seven patients with locally advanced breast cancer were treated with multimodality therapy comprising of six pulses of neo-adjuvant chemotherapy (doxorubicin, cyclophosphamide, vincristine and prednisolone) at 21-day intervals, followed by surgery (breast conservation or mastectomy) with appropriate axillary surgery, radiotherapy and adjuvant tamoxifen. The serum concentrations of acute phase proteins, C-reactive protein (CRP), á-1-anti-trypsin, albumin and transferrin were measured in serum taken prior to commencement of treatment. Patients were followed up for a median of 31 months and their clinical and histological responses and overall survival recorded. Univariate analyses revealed that tumour stage (p=0.01), clinical lymph node status (p=0. 02) and pre-treatment levels of serum albumin (p=0.002) and á-1-anti-trypsin (p=0.06) predicted overall survival. Using the Cox proportional hazards model reduced pre-treatment levels of serum albumin (p<0.00001), progressive lymph node involvement with tumour (p<0.005), and advancing tumour stage (p<0.01) were independent prognostic indicators for a poorer survival in patients with locally advanced breast cancer receiving neo-adjuvant chemotherapy.

Acute-Phase Proteins↗
PubMed1998

Serum albumin: a prognostic indicator in patients with colorectal cancer.

Various prognostic factors for survival have been identified in patients with colorectal cancer. However, although it has been suggested that the pre-treatment serum albumin concentration is a prognostic indicator in certain malignant diseases (melanoma, prostate cancer, leukaemia), its value in patients with colorectal cancer remains unclear. This study investigated the prognostic value of serum albumin in this patient group. A total of 431 patients presenting to the Professorial Surgical Unit between 1972 and 1985 were analysed in this study. Using the Cox proportional hazard model, age, tumour stage (Dukes' stage) and tumour differentiation were shown to be independent prognostic factors for survival in patients with localized colorectal cancer. In addition, the pre-treatment serum albumin concentration was found to be an independent prognostic indicator. This is the first such documentation for patients with 'curable' colorectal cancer.

Adult↗
PubMed1997

Apoptosis in colorectal carcinoma occurring in patients aged 45 years and under: relationship to prognosis, mitosis, and immunohistochemical demonstration of p53, c-myc and bcl-2 protein products.

The aim of this study was to ascertain whether apoptotic counts have prognostic significance in colorectal cancer and if such counts are related to the expression of proteins implicated in cell cycle regulation. Material from a cohort of patients aged 45 years or less with colorectal carcinoma was re-examined to determine apoptotic and mitotic counts by light microscopy, in addition to assessing p53, c-myc, and bcl-2 protein status by immunohistochemistry. The apoptotic index in the 74 patients who were alive or who had died of colorectal carcinoma ranged from 1.2 per cent to 12.3 per cent and exhibited independent prognostic significance, with high counts predicting better survival (P = 0.02). Mitotic counts were not related to survival, despite a close correlation with apoptosis (r = 0.85). Tumours regarded as not staining with the CM1 antibody for p53 protein demonstrated higher apoptotic counts, compared with those that stained (medians 5.2 and 4.0 per cent, respectively; P = 0.03), but p53 expression was found not to be related to survival. The 68 tumours which stained for c-myc appeared to exhibit higher mitotic counts than those that did not. bcl-2 was detected in only four tumours. The latter two proteins exhibited no apparent relationship to the apoptotic index or survival. Although these results indicate a potential role for apoptotic counting in prognostic prediction in colorectal tumours, this is an uncommon group of patients who exhibited some atypical features. The likelihood of a proportion of cases arising within hereditary non-polyposis colorectal cancer syndrome may limit the application of the findings to a more general population with cancer of the colon and rectum. Further work is required, including critical measurement of reproducibility and assessment of the relative impact of this parameter compared with 'traditional' prognostic markers.

Adolescent↗
PubMed1997

The psychological and psychiatric effects of rIL-2 therapy: a controlled clinical trial.

It has been suggested that recombinant interleukin-2 (rIL-2) may cause pyschological and psychiatric problems, although the effects of rIL-2 on its own have not been well documented. To evaluate these effects, 17 patients with advanced colorectal cancer took part in a randomised, parallel group study of rIL-2 with chemotherapy (5-fluorouracil and leucovorin) versus chemotherapy alone. Patients were assessed regularly by means of various psychometric tests including the Hospital Anxiety and Depression Scale, the Mood Rating Scale, the Mini-Mental State Examination, the Digit Symbol Substitution Test, the Trail-Making Test and the Benton Revised Visual Retention Test. Rigorous discontinuation criteria were applied to ensure that the effect of time-related variables did not influence the results. Compared with patients who were given chemotherapy alone, patients receiving immunochemotherapy reported reduced energy, impaired confidence, higher depressed mood and more confusion. Immunochemotherapy was rated as more distressing than chemotherapy alone and patients reported a greater incidence of appetite impairment, weight loss, poor concentration and fever. Cognitive assessments indicated that brain dysfunction can be caused by rIL-2. Compared with the control group, patients receiving immunochemotherapy showed significant impairment on Trail Making Test B and the Digit Symbol Substitution Test. One patient developed repeated transient psychotic episodes associated with rIL-2 infusions and another regularly became confused. These effects were not due to sleep deprivation or pyrexia. Treatment with rIL-2 should not be discarded on psychosocial grounds, although in each case the psychological morbidity and adverse effects on quality of life need to be balanced carefully against potential therapeutic benefits.

Antimetabolites, Antineoplastic↗
PubMed1997

The management of patients with advanced cancer (III).

In this third article in the series, the management of patients with symptoms arising as a consequence of metastatic disease involving peripheral nerves, the spinal cord and the brain are discussed. In particular, pain, spinal cord compression and symptoms due to either raised intracranial pressure or specific neurological deficits may substantially impair the quality of life in patients with advanced cancer. Pain control, using both medical and surgical treatments, are discussed. The principles underlying the diagnosis and treatment of metastases to the vertebral column and spinal cord, as well as intracranial deposits, are outlined.

Analgesia↗
PubMed1997

The management of patients with advanced cancer (II).

In this second article in the series, obstruction of hollow viscera in patients with advanced malignant disease is discussed. The obstruction of such structures can be associated with the development of painful and incapacitating symptoms, often in patients who have a limited life expectancy. This obstruction may be caused by the primary tumour, compression from adjacent tumour-draining lymph nodes, the presence of metastases distant from the site of the primary tumour or to adhesions within the abdominal compartment (usually as a result of previous surgery). The organs most often affected are the oesophagus, the intestine (small and large), the biliary tree and the genito-urinary tract. Obstruction of each of these organs and its management is discussed in more detail below.

Cholestasis↗
PubMed1997

Modulation in vitro of human natural cytotoxicity, lymphocyte proliferative response to mitogens and cytokine production by essential fatty acids.

Essential fatty acids (EFA) have been shown in animal studies to have a differential effect on various aspects of immune reactivity. However, there have been few studies in humans. Therefore, we elected to investigate the effects of a variety of EFA [gamma-linolenic acid (GLA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] in vitro on human blood lymphocyte reactivity, cytokine secretion and natural cytotoxicity. The proliferative response to polyclonal mitogens (phytohaemagglutinin, pokeweed mitogen, concanavalin A), as measured by [3H]thymidine incorporation into newly synthesized lymphocytes, was inhibited (P < 0.05) by all EFAs tested, in a dose-dependent manner (3-15 micrograms/ml). The greatest inhibition of proliferation was caused by EPA and DHA. Similarly, EPA, DHA and GLA significantly reduced cytotoxic activity [expressed as lytic units, using 51 chromium-release assays natural killer (NK) (K562 cells) and lymphokine-activated (LAK) (Daudi cells) cells] (P < 0.05) in a concentration-dependent manner (5-50 micrograms/ml), without affecting cell viability. EPA and DHA exhibited greater suppression than GLA. Furthermore, the inhibition of cell proliferation and suppression of natural cytotoxicity was associated with marked decrease in cytokine [interleukin-1 (IL-1), IL-2, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma)] production in vitro. Our findings demonstrate that EFAs (GLA, EPA, DHA) have the potential to inhibit significantly various aspects of human lymphocyte cell-mediated and humoral immune reactivities.

Cell Culture Techniques↗
PubMed1997

The value of peri-operative nutrition in the sick patient.

In summary, therefore, the provision of TPN to malnourished patients in the pre-operative period reduces the incidence of post-operative complications, but does not affect post-operative mortality. It is likely that the provision of nutrition by the enteral route is as effective as that by the parenteral route, and may have the extra benefit of resulting in a reduction in infectious complications when compared with patients receiving TPN. Furthermore, the use of enteral nutritional support in the post-operative period may also reduce both septic and major complications, but does not alter mortality. The use of specific combinations of nutrients appears to offer the greatest promise in the use of peri-operative nutritional support. The initial studies reported to date demonstrate reductions in post-operative morbidity, but again there are no benefits on mortality. However, further studies to determine the optimal combinations of nutrients for use in patients in the peri-operative period are urgently required.

Enteral Nutrition↗