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Biomedical subjects

D M Dent

Publications and source records attributed to D M Dent.

At least 19 recordsLinked to original sources
PubMed2000

Expression of p53 and p21waf1/cip1 in gastric carcinoma: lack of inter-relationship or correlation with prognosis.

AIMS: The cell cycle regulators p53 and p21waf1/cip1 are expressed variably in human cancers. We investigated their expression in gastric carcinoma and determined their inter-relationship and prognostic significance. METHODS: Immunohistochemistry was used to determine their expression in material from 100 resected specimens of gastric carcinoma, and comparison was then made of the degree of expression between each, with conventional clinicopathological indices and with survival. RESULTS: Positivity was found with p53 (40%) and p21 (75%). There was no significant correlation between the expression of each individual marker, nor between each marker and 5-year survival. There appeared to be an association between p53 expression and lymph node metastases, and a higher frequency of p21waf1/cip1 expression in males. CONCLUSIONS: The expression of p53 and p21waf1/cip1 as detected by immunohistochemistry were of no value in predicting the prognosis of patients with gastric carcinoma.

Biomarkers, Tumor↗
PubMed2000

One-stage immediate breast and nipple-areolar reconstruction with autologous tissue I: a preliminary report.

This preliminary report discusses 7 patients with early breast cancer (mean age, 48 years) who underwent one-stage breast reconstruction. Reconstruction was achieved using a deepithelialized transverse rectus abdominis musculocutaneous (TRAM) flap placed in a pocket created by a skin-sparing mastectomy. Areolar reconstruction is performed by harvesting the areola as a full-thickness graft from the mastectomy specimen, and nipple reconstruction is achieved with a CV flap (in zone II of the TRAM flap), which is deepithelialized and covered with a full-thickness graft from the areola. In all patients a contralateral reduction or mastopexy was performed. Recent evidence suggests that not all patients with early breast cancer have areolar involvement, and that certain prognostic factors can be used to predict the likelihood of tumor involvement. A number of large studies have shown that in patients with early breast cancer, when the tumor is situated more than 5 cm from the nipple-areolar complex, tumor involvement of the nipple-areolar complex is most unlikely. No patients in this study had histological evidence of nipple involvement by cancer. The aesthetic results were very satisfactory in 5 of 7 patients. One patient who developed sepsis of the TRAM flap had an unsatisfactory result. The other complications that occurred were minor and self-limiting. The advantages of single-stage breast reconstruction are financial and psychological. In addition, the patient attains homogenous nipple-areolar reconstruction. Areolar reconstruction is achieved with the best possible option--areola. This preliminary report suggests that in a select group of patients with early breast cancer, when the tumor is more than 5 cm from the nipple-areolar complex, the areola may be preserved. The aesthetic results in these patients was considered satisfactory. However, long-term studies are required to confirm the oncological safety of this technique.

Adult↗
PubMed2000

Breast cancer incidence and determinants of cancer stage in the Western Cape.

OBJECTIVE: To describe the overall and age-specific incidence rates for breast cancer and determinants of the stage of breast cancer at the time of diagnosis in the Western Cape, South Africa. METHODS: Data were derived from a case-control study of the association between injectable progestagen contraceptives and breast cancer conducted over a 4-year period from January 1994 to December 1997. In all, 485 cases were drawn from a study population consisting of coloured and black women under the age of 55 years, who presented with a first occurrence of invasive breast cancer at two tertiary hospitals in Cape Town. A questionnaire was administered and information on a large number of variables was recorded. RESULTS: The 249 cases who were interviewed during the first 2 years of the study constituted the numerator for estimates of incidence rates. The overall incidence rate was 23.1 per 100,000 women per year. The incidence rate for coloured women was 25.6 per 100,000, almost twice that for black women (14.7 per 100,000). The incidence rate in urban areas was 26.6 per 100,000, almost twice that in the rural areas (16.3 per 100,000). Stages 1 and 2 accounted for 57.8% of the cases. Early stage at diagnosis was significantly associated with a higher educational level, membership of a medical aid, residence in an urban area and a positive family history. CONCLUSION: The data suggest that there is scope for improvement in the detection of the disease through education and access to diagnostic measures, particularly in rural and disadvantaged populations.

Adult↗
PubMed1999

Breast tumour cell-induced down-regulation of type I collagen mRNA in fibroblasts.

This study investigated the modulation of type I collagen gene expression in normal fibroblasts by breast tumour cells. Northern analysis of total RNA extracted from stages I, II and III breast tumour tissue revealed that collagen mRNA levels were elevated in stage I tumours compared to the adjacent normal breast tissues, whereas they were decreased in stages II and III breast tumours. This aberrant collagen gene expression was confirmed by non-radioactive RNA:RNA in situ hybridization analysis of 30 breast carcinomas which localized the production of type I collagen mRNA to the stromal fibroblasts within the vicinity of the tumour cells. In order to determine whether the tumour cells were directly responsible for this altered collagen production by the adjacent fibroblasts, breast tumour cell lines were co-cultured with normal fibroblasts for in vitro assessment of collagen and steady-state collagen RNA levels. Co-culture of tumour cells and normal fibroblasts in the same dish resulted in down-regulation of collagen mRNA and protein. Treatment of the fibroblasts with tumour-cell conditioned medium also resulted in decreased collagen protein levels but the mRNA levels, however, remained unaltered. These results suggested that the tumour cells either secrete a labile 'factor', or express a cell surface protein requiring direct contact with the fibroblasts, resulting in down-regulation of collagen gene expression. Modulation of the ECM is a common characteristic of invading tumour cells and usually involves increased production of collagenases by the tumour cells or stromal fibroblasts. This study showed that tumour cells were also able to modulate collagen mRNA production by stromal fibroblasts, which may facilitate tumour cell invasion and metastasis.

Blotting, Northern↗
PubMed1999

Factors leading to local recurrence or death after surgical resection of phyllodes tumours of the breast.

BACKGROUND: Local recurrence and death from metastases are occasional, but consistent, themes in reports of patients with phyllodes tumours. Factors that might contribute to these outcomes were sought. METHODS: Data from 38 patients with a phyllodes breast tumour were reviewed retrospectively, reclassifying the pathological material using the Pietruszka and Barnes criteria. RESULTS: At a median of 12 months, nine patients had developed a local recurrence and four had died from metastases. Following local excision in 24 patients (for diagnosis in 13, for 'fibroadenoma' in nine and for phyllodes tumour in two patients), 13 had no further surgery and five had local recurrence (three of eight benign tumours, two of two malignant tumours). Wide local excision or mastectomy in 18 patients was followed by four recurrences (one of eight borderline tumours, three of ten malignant tumours). All patients with recurrence had margin involvement on histological examination, but not all patients with margin involvement developed recurrence. Lack of statistical correlation between local recurrence and age, delay, size, grade or type of surgery was confounded by selection bias for more extensive surgery for malignant tumours. Death correlated with size (P = 0.05) and grade (P = 0.03) of tumour. CONCLUSION: Inadequate preoperative diagnosis ('fibroadenoma' or failure of triple assessment) frequently led to local excision with positive margins. Without revision this often resulted in local recurrence. Local recurrence of any grade was usually followed by further recurrence. Death was related to tumour size and histological grade, confirming these as prognostic factors.

Adolescent↗
PubMed1999

Fragmentation pattern of mucins in normal and diseased gastric mucosae: a glycoprotein fractionates with gastric mucins purified from mucosal scrapings of cancer and peptic ulcer patients.

BACKGROUND/AIMS: Gastric cancer, a fatal malignancy, is prevalent in the Western Cape region of South Africa. The aim of this study was a biochemical characterisation of gastric mucins in this disease, compared with gastric ulceration and controls from transplant donors. METHODS: Mucins were extracted in a denaturing medium (to prevent endogenous proteolysis) and purified by caesium chloride density gradient ultracentrifugation. Analysis of mucin was by gel filtration, SDS-PAGE and Western blotting methods. RESULTS: All samples of mucin when analysed by gel filtration were found to contain polymeric glycoprotein together with varying amounts of lower-molecular-weight glycoprotein. SDS-PAGE and Western blot analysis showed that diseased stomachs had glycopeptides of a wider range in size and antigenicity with a greater number of smaller fragments immunoreactive to monoclonal antibodies 2-12M1 and 9-13M1. We identified by SDS-PAGE a glycoprotein which co-fractionates in a caesium chloride density gradient with mucins isolated from gastrectomy specimens resected for carcinoma and peptic ulceration and which was absent from mucins of the transplant donor control group. This neuraminidase-sensitive glycoprotein resisted dissociation from mucin during purification in a 3.5 M CsCl density gradient but was partially separable by Sepharose 2B gel chromatography and heat treatment (100 degrees C, 2.0 min) in SDS. Chemical analysis of the glycoprotein by HPLC favours it being an N-linked glycoprotein. Its non-ideal electrophoretic properties make its exact size estimation difficult and we ascribe to it a broad size range of Mr approximately 55-65 kD. CONCLUSION: We conclude that mucins from diseased stomachs were more degraded than those from donors and that the diseased mucosa reproducibly secretes a Mr approximately 55-65 kD glycoprotein, the role of which needs to be established.

Adenocarcinoma↗
PubMed1996

Illness experiences and health recovery behaviors of patients in southern Appalachia.

The purpose of this exploratory study was to gain a better understanding of the influences of Appalachian culture and rural living on illness experiences and health recovery behaviors. The study sample consisted of 257 randomly selected adult patients admitted to medical-surgical units in eight hospitals in West Virginia. Patients completed interviews in the hospital and by phone and in their homes 1 month after hospital discharge. In addition, 203 nurses and 79 physicians completed a values survey and decisional control questions. The triangulation of quantitative and qualitative data suggested that culture, age, gender, and rural residence affected responses to illness and recovery. Traditional values and roles persisted in this population and influenced health behaviors. The findings of this study support the need for culturally sensitive care and for innovative education programs to reduce health risks.

Adaptation, Psychological↗
PubMed1996

A re-evaluation of isotope screening for skeletal metastases in node-negative breast cancer.

OBJECTIVE: To determine the accuracy and cost-effectiveness of skeletal scintigraphy in women with early, node-negative (T1-2N0M0) breast cancer. DESIGN: Retrospective, where scintigraphic prediction of metastases was compared with the criterion standard of radiological confirmation during a follow-up of 5 - 10 years. SETTING: Tertiary referral breast clinic at Groote Schuur Hospital. PATIENTS: Six hundred and seventy-three women with clinical T1-2N0M0 breast cancer who had skeletal scintigraphy between 1974 and 1987, and who had been followed up for more than 5 years. INTERVENTIONS: Initial skeletal scintigraphy, annual follow-up with radiological examination of symptomatic areas. MAIN OUTCOME MEASURES: Correlation of the sites indicated by scintigraphy with the initial presence or later development of metastases at 1 - 10 years, and the cost. RESULTS: Five hundred and sixty-one (83.4%) scans were normal, 35 (5.2%) indicated benign processes, and 77 (11.4%) were suggestive or diagnostic of metastatic disease, with radiological confirmation in 3 (initial detection rate 3/673, 0.44%; accuracy rate 3/77, 3.9%). Of the remaining 74 abnormal scans without radiological confirmation of metastases, 62 has a focus at a single site, and 45 were of low intensity and equivocal, with no apparent explanation. The cumulative sensitivity for predicting site of metastases at 1 year was 33% (3/9) and the positive predictive value 4.0% (3/75). At 10 years the sensitivity was 5.0% (3/60) and the positive predictive value 5.0% (3/65). The total cost of screening was calculated to be R323 460.00, suggesting that the cost for each patient in whom metastases were detected was R64 629.00. CONCLUSION: While scintigraphy may be of value in symptomatic or more advanced disease, screening of node-negative women had a minimal detection rate, was expensive and cannot be supported.

Bone Neoplasms↗
PubMed1996

Mastectomy with axillary clearance versus mastectomy without it. Late results of a trial in which patients had no adjuvant chemo-, radio- or endocrine therapy.

OBJECTIVE: Long-term outcome of comparison of mastectomy with axillary clearance to mastectomy without it. DESIGN: Second analysis of a terminated prospective randomised trial. SETTING: The Breast Clinic, Groote Schuur Hospital, Cape Town. PATIENTS: Ninety-five women aged under 76 years with stages 1 and 2 (T1-2 NO-1 MO) breast cancer. INTERVENTIONS: Radical mastectomy (mastectomy and formal axillary dissection with pectoral muscle excision) or simple mastectomy (mastectomy without axillary dissection if nodes were not clinically palpable, or local excision of the nodes if they were). OUTCOME MEASURES: Loco-regional recurrence and survival. RESULTS: Whereas initial analysis at 40 months had showed more axillary recurrences (P = 0.056) in the simple mastectomy group (leading to the termination of the trial), this difference has disappeared at 10 years (P = 0.113). There was no difference in rate of recurrence at all other sites, time to recurrence, or survival rates at 40 months or at 10 or 25 years. CONCLUSIONS: Full axillary clearance offered no better long-term loco-regional control or survival. Early analysis and marginally significant differences in axillary recurrence prompted premature termination of this trial.

Adult↗
PubMed1995

Non-operative management of breast masses diagnosed as fibroadenoma.

A 7-9-year study was undertaken in 99 female patients (median age 20 years), 56 of whom had single and 43 multiple fibroadenomas (total 279). Thirty-four women with 58 masses (21 per cent) were lost to follow-up. Twenty-eight women with 73 masses (26 per cent) subsequently underwent excision at a median of 10 (range 3-59) months for single and 38 (1-110) months for multiple fibroadenomas (P = 0.03), with histological confirmation in 71 and other benign disease in two cases. There was resolution of 107 masses (38 per cent of those entered into the study, 72 per cent of those not lost or excised), leaving 41 persisting masses (15 per cent of those entered into the study, 28 per cent of those not lost or excised). The actuarial probability of disappearance was 0.46 at 5 years and 0.69 at 9 years (Kaplan-Meier analysis). There was no difference in the rate of resolution when 56 single lesions were compared with 223 multiple lesions, or when 192 lesions measuring 2 cm or less in diameter were compared with 87 greater than 2 cm. Resolution was significantly more frequent in women aged 20 years or less than in those who were older (P < 0.01). Non-operative management remains a safe approach in selected women and should be followed by resolution of half of fibroadenomas at 5 years.

Adolescent↗