Biomedical subjects
Publications and source records attributed to K Clough.
Fine needle aspiration (FNA) and core biopsy (CB) are efficient alternatives to surgical biopsy: FNA provides a sampling of cells and is very cost effective. The main limits are insufficient sampling rate and the impossibility to diagnose invasion. CB allows architectural description and the diagnosis of specific benign and malignant lesions, but is more expensive and time-consuming.
BACKGROUND: To document the role of neoangiogenesis in the progression of breast carcinomas, intratumoral vascular density (ITVD) was assessed and compared to pathologic data and disease outcome in a series of 685 cases. METHODS: Patients were registered between 1981 and 1988 at the Curie Institute. Tumors corresponded to small size (< or = 30 mm) invasive carcinomas, 71% of which were axillary lymph node-negative. In all cases, conservative surgery was the initial therapeutic procedure. The median follow-up was 10.8 years. ITVD was retrospectively determined as the number of immunostained (anti-F8RA/vWF antibody) vessels in an area of 1.2 mm(2). The prognostic value of ITVD regarding overall survival, locoregional recurrence-free, and metastasis-free intervals was assessed in uni- and multivariate analyses. RESULTS: Microvessel count ranged from 5--245 per 1.2 mm(2) field. The median value was 62, and the mean was 67. The median was chosen as a cut point for statistical analysis. ITVD was found to be inversely linked to tumor size (P < or = 0.0001) and histologic grade (P = 0.005), and directly linked to vascular invasion (P = 0.02). In uni- and multivariate analysis, no significant link was found between ITVD and disease outcome, even after adjustment on histologic grade and tumor size. CONCLUSIONS: ITVD was inversely correlated to tumor size and histologic grade in our series of small-size breast carcinomas. No significant link between ITVD and disease outcome was observed. Evaluation of the role of angiogenesis in tumor progression should be based on the discriminative assessment of mature and/or activated vessels.
BACKGROUND: Initial debulking surgery followed by chemotherapy is the current treatment for International Federation of Gynecology and Obstetrics Stage IIIC/IV ovarian carcinoma but has a limited efficacy when optimal cytoreduction is not achieved at the end of the surgical procedure. An alternative treatment for these patients could be neoadjuvant chemotherapy. The purpose of this retrospective study was to report the results of neoadjuvant chemotherapy in operable patients (no medical contraindication to surgery) presenting with primary unresectable tumors. METHODS: Between January 1996 and March 1999, operable patients presenting with Stage IIIC or IV ovarian carcinoma underwent, in six French gynecologic oncology departments, surgical staging to evaluate tumor resectability. When the tumor was deemed unresectable by standard surgery, the patient received three to six cycles of platinum-based neoadjuvant chemotherapy according to the response and the center's usual protocol. Patients were surgically explored after completion of neoadjuvant chemotherapy when the tumor did not progress during treatment. Debulking was performed during this secondary surgery when a response to chemotherapy was observed. RESULTS: Fifty-four patients were treated by neoadjuvant chemotherapy. The first surgical staging procedure was laparoscopy in 33 patients (61%) and laparotomy in 21 patients (39%). The median number of neoadjuvant chemotherapy cycles was 4 (range, 0-6). Forty-three patients (80%) responded to neoadjuvant chemotherapy and then tumors were debulked. Optimal cytoreduction was obtained in 39 patients (91% of the patients who underwent debulking) and with standard surgery in 32 patients (82%). For patients whose tumors were optimally debulked, blood transfusions were administered to 17 patients (43%), median intensive care unit stay was 0 days (range, 0-7 days), and median postoperative hospital stay was 10 days (range, 4-62 days). Median overall survival for the total series was 22 months. Survival was better for patients debulked after neoadjuvant chemotherapy compared with patients with nondebulked tumors (P < 0.001). CONCLUSIONS: Neoadjuvant chemotherapy for primary unresectable ovarian carcinoma leads to the selection of a subset of patients sensitive to chemotherapy in whom optimal cytoreduction can be achieved after chemotherapy by standard surgery in a high proportion of cases. Conversely, aggressive surgery can be avoided in patients with initial chemoresistance, in whom the prognosis is known to be poor regardless of treatment.
The potential of telemedicine to improve services for patients suffering from coronary heart disease (CHD) was explored. Key issues surrounding the delivery of CHD services in London were identified, such as a shortage of skilled staff, the need for appropriate patient information and problems with waiting times, particularly for diagnostic test results. Telemedicine has the potential to improve service delivery in each of these areas. It is unlikely that some of the targets for CHD service delivery set out by the Department of Health's National Service Frameworks can be met without the use of telemedicine.
The current extension of the indications for adjuvant chemotherapy, which predisposes to early menopause, and the media coverage of the benefits of hormone replacement therapy (HRT) have led patients with a history of breast cancer to seek treatments for estrogen deprivation. In breast cancer survivors, most physicians avoid HRT because of concern regarding the potential promotion of growth of occult malignant cells by estrogens, due to the estrogen dependence of breast cancer. Soy phytoestrogens are being promoted as the 'natural alternative' to HRT and have been available without restrictions for several years as nutritional supplements. In this paper, data on the complex mammary effects of phytoestrogens in epidemiological studies, in in vitro studies, as well as in in vivo studies on animal carcinogenesis are reviewed. The potential benefits and risks of phytoestrogens are analyzed, and the prescription of phytoestrogens to postmenopausal women after breast cancer and the coprescription with the anti-estrogen tamoxifen are discussed. The absence of controlled trials and technical checking of extraction and titration in these preparations on 'free sale' raise a new problem in terms of public health and justify close reasoning and a cautious attitude of physicians, as well as straight information given to women, especially after breast cancer.
The predictive value of ERBB2 amplification/expression to doxorubicin use is controversial. Preoperative chemotherapy, followed by the pathological assessment of tumour response to treatment provide optimal conditions for the evaluation of the predictive value of biological parameters. We report here data on the predictive value of ERBB2 in a series of 54 cases of breast cancer treated by preoperative high-dose anthracycline-based chemotherapy. Our series consisted of 26 women presenting an inflammatory breast cancer (IBC) and of 28 women with poor prognosis primary cancer (PPPC). Patients received a total of four cycles with doxorubicin (75 mg/m(2) for IBC or 70 mg/m(2) for PPPC) and cyclophosphamide (6 g/m(2) for IBC or 1400 mg/m(2) for PPPC), every 21 days. ERBB2 expression was determined by immunohistochemistry (clone CB11) performed on a tumour biopsy taken before chemotherapy. All patients underwent surgery as a second step of treatment, and the tumour response was assessed on pathological specimens. A complete pathological response was observed in 24 of the 54 cases (44%) (95% confidence interval (CI), 31-57). Pathological complete response was positively correlated with high histological grade (P=0. 02) and with the absence of oestrogen (P=0.003) or progesterone (P=0. 02) receptor expression. ERBB2 overexpression was found in 18 of the 54 cases (33%). A complete pathological response was observed in 33% of these cases (6/18). This figure was not significantly different from the 50% rate of complete response observed for tumours with no detectable ERBB2 expression (18/36). In this small series, ERBB2 overexpression was not a significant predictive marker of the pathological response to high-dose doxorubicin-based chemotherapy.
We carried out a study to explore the potential of telemedicine and telecare to improve health-care for the population served by a health centre based in Deptford in south-east London. A wide range of potentially useful telemedicine and telecare applications was identified, nine of which could provide some immediate benefit. Other requiring new approaches to the delivery of care involved some reengineering of services. Some suggestions focused on the need to integrate information technology with service provision. Other suggestions raised strategic questions, the most important of which concerned the routes of access to health-care.
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Conservative treatment of multifocal breast cancer is still very controversial. This retrospective study concerns 56 patients with stage I or II multifocal breast cancer who underwent conservative treatment at the Institut Curie from January 1983 to December 1989. These patients (group 1) were matched with 132 patients with multifocal lesions treated by mastectomy (group 2). Surgical treatment consisted of a single wide lumpectomy followed by external radiotherapy. Adjuvant systemic therapy and regional nodal irradiation were administered as indicated by current protocols. The actuarial 5-year overall survival rate was 94% 6 in group 1, and 90% 6 in group 2 (NS). The actuarial 5-year ipsilateral breast recurrence rate was 11% 8 in group 1, and 11% 5 in group 2 (NS). In group 1 patients, the ipsilateral breast recurrence rate was related neither to type of multifocality nor to presence of intra ductal breast carcinoma, nodal status, tumor margins, radiotherapy boost, or distance between tumors. Consequently, conservative treatment of multifocal breast cancers which can be completely removed by a single lumpectomy seems, when technically feasible, an alternative to mastectomy.
A heterohybridoma cell line producing the human monoclonal antibody (MoAb) MDT.1 has been established. The heavy chain of MoAb MDT.1 is encoded by the VH gene segment V4-34 (previously designated VH4-21), and the light chain is encoded by the V kappa 1-L12a gene segment, both in germline configuration. MDT.1 has reactivity against lipid A, double- and single-stranded DNA, red blood cell associated i antigen, and ganglioside antigens. In a panel of tumour cell lines, MDT.1 reacted specifically with melanoma cells and other tumour cells of neuroectodermal origin. Cellular recognition appears to be via tumour-associated ganglioside antigens, and may involve the minimal essential epitope NeuNac alpha 2-->3Gal beta 1-->-4Glc-. Binding to ganglioside antigen is inhibited by the monoclonal anti-idiotypic antibody 9G4. Since the 9G4 idiotope is located in framework region 1 (FWR1) of V4-34-encoded antibodies, this region is likely to be involved, either directly or indirectly, in ganglioside binding. The complementarity-determining region 3 (CDR3) of MDT.1 is arginine rich, with five out of 12 residues being arginine and these residues are candidates for interaction with the negatively charged ganglioside. The ability of MoAb MDT.1 to recognise ganglioside antigens is associated with potentially useful anti-tumour activity.
This study was designed for the histopathological, cellular and biochemical characterization of a skin lesion removed surgically from a young male several months after accidental exposure to cesium-137, with an emphasis on expression of transforming growth factor beta1 (TGFB1) and tumor necrosis factor alpha (TNFA) and the occurrence of apoptosis. Under a hypertrophic epidermis, a highly inhomogeneous inflammatory dermis was observed, together with fibroblastic proliferation in necrotic areas. Immunostaining revealed overexpression of TGFB1 and TNFA inside the keratinocytes of the hypertrophic epidermis as well as in the cytoplasm of the fibroblasts and connective tissue of the mixed fibrotic and necrotic dermis. Inside this dermis, the TUNEL assay revealed areas containing numerous apoptotic fibroblasts next to areas of normal viable cells. Overexpression of TGFB1 was found in the conditioned medium and cellular fractions of both hypertrophic keratinocytes and fibrotic fibroblasts. This overexpression lasted for at least three passages in tissue culture. The present observations were consistent with the central role of TGFB1 in the determination of chronic radiation-induced damage to the skin and a significant involvement of TNFA. In addition, programmed cell death appeared to take place during the remodeling of the mixed fibrotic and necrotic tissue.
BACKGROUND: The early diagnosis of nonpalpable breast lesions is a medical challenge because of the low specificity of different radiologic modalities. Fine-needle aspiration cytology (FNAC) assisted by a stereotactic guidance is an adjunctive diagnostic approach in the management of these lesions. The primary purpose of this article was to assess the diagnostic accuracy of FNAC in patients with nonpalpable breast lesions. METHODS: Three hundred and seventy-one lesions from 357 patients (all female) underwent FNAC using the stereotactically guided technique. Of these cases, 243 lesions from 238 patients subsequently were acquired by surgical excisional biopsies and formed the basis of this study. Statistical analyses of the cytologic and the histologic diagnoses of these cases were performed. RESULTS: Histologically, 107 lesions (44%) were benign and 136 lesions (56%) were malignant. Of the 136 malignant lesions, cytology was concordant in 73 lesions (53.7%), suspicious in 15 lesions (11.0%), false-negative in 12 lesions (8.8%) (benign), and unsatisfactory in 36 lesions (26.5%). Among the 107 benign lesions, cytology was concordant with histology in 75 lesions (70.1%), whereas 4 lesions (3.7%) and 28 lesions (26.2%) were cytologically suspicious and unsatisfactory, respectively. No false-positive cytologies were found in the current series. CONCLUSIONS: The current prospective study indicates that mammography combined with FNAC provides an accurate and practical diagnostic approach for the majority of nonpalpable lesions. Patients with unsatisfactory and false-negative lesions should undergo excisional biopsy.
BACKGROUND: The value of ultrasound-guided fine-needle aspiration cytology (FNAC) in the diagnosis of nonpalpable breast lesions remains a subject of debate. To determine the accuracy of this procedure in these lesions, a comparative analysis with open surgical biopsy in 188 patients was performed. METHODS: Six hundred and fifty-four nonpalpable breast lesions detected by ultrasound in 585 patients were subjected to FNAC. Of these, 198 lesions (30.3%) from 188 patients were surgically excised. RESULTS: Histologically, 105 lesions (53%) were malignant and 93 (47%) were benign. Among carcinomas, 65 cases (61.9%) were concordant, whereas 21 cases (20%) were suspicious, 12 cases (11.4%) were false-negative (benign), and 7 cases (6.7%) were unsatisfactory for diagnosis. Among benign lesions, 80 cases (86%) were concordant, whereas 5 cases (5.4%) were suspicious, and 8 cases (8.6%) were unsatisfactory. No false-positive diagnoses were made. The sensitivity of the FNAC method was 87.8%, the specificity was 94.5%, and the positive predictive value was 94.6%. CONCLUSIONS: These results indicate that, with the exception of random microcalcified lesions, ultrasound-guided FNAC is a valuable and reliable technique in the diagnosis of nonpalpable breast lesions.
To document whether c-erbB-2 over-expression or p53 accumulation in tumour cells was predictive of response to chemo- or radiotherapy, we analyzed a population of patients with breast cancer assigned to neo-adjuvant therapy (median follow-up: 54 months). T2/T3-N0N1b-M0 tumours (329 cases) were treated either by FAC chemotherapy or by radiotherapy before surgery, and the clinical response was classified as complete or incomplete. Expression of c-erbB-2 and p53 was retrospectively evaluated by immunohistochemistry. Proliferation rate was assessed by means of MIB-1 antibody and by S-phase fraction. A complete response to chemotherapy was observed in 38/167 patients (23%). Complete response rate was 20% in c-erbB-2-negative tumours, and rose to 31% in tumours with c-erbB-2 over-expression, but this trend was not statistically significant. There was no correlation between p53 staining and response to treatment, whereas chemosensitivity was found correlated with histological grade and S-phase. A complete response to radiotherapy was observed in 64 of the 156 evaluable patients (41%). Complete response rate was 41% in c-erbB-2- or p53-negative tumours, 54% in tumours with c-erb-B-2 over-expression, and 44% in tumours with p53 accumulation. There was no correlation between response to radiotherapy and histological grade or proliferative rate. No prognostic value was found for c-erbB-2 or p53 expression, whereas the 5-year survival rate was 85% for patients presenting a tumour with a low proliferating index (MIB-1 < 10%), and 68% for patients presenting a tumour with a high proliferative index. In multivariate analysis, node status (RR = 2), MIB-1 immunostaining (RR = 2), and tumour size (RR = 1.8) were found to be associated with survival. These results indicate that c-erbB-2 or p53 expression is not significantly associated with tumour response to neo-adjuvant chemo/radiotherapy in our series of breast cancers.
PURPOSE: To determine whether the prognosis of invasive cancers of the uterine cervix is related to the type of human papillomavirus (HPV) associated with the tumor. PATIENTS AND METHODS: Two hundred ninety-seven patients with invasive cervical cancer were prospectively registered from 1986 to 1994. HPV typing was performed on DNA extracted from frozen tumor specimens by means of Southern blot hybridization (SBH) and polymerase chain reaction (PCR) techniques. The median follow-up was 38 months. RESULTS: HPV sequences were detected in 246 patients (83%): 150 patients had HPV16, 31 patients had HPV18, and 14 patients had one of the intermediate-oncogenic-risk HPV types (HPV31, 33, 35, 52, 58). In 51 patients, HPV type remained undetermined, and in 51 patients, no viral sequences were found. No significant associations were observed between virologic data and tumor stage or node status. The 5-year disease-free survival (DFS) rate was 100% for patients with intermediate-risk HPV-associated tumors, 58% for patients with HPV16-positive tumors, and 38% for patients with HPV18-positive tumors (P = .02). In multivariate analysis, patients with HPV18-associated tumors had a relative risk (RR) of death 2.4 times greater (95% confidence interval [CI], 1.29-4.59) than that for patients with HPV16, and 4.4 times greater (95% CI, 3.48-5.32) than that for patients with a tumor associated with a viral type different from HPV16/18. CONCLUSION: The prognosis for invasive cancers of the uterine cervix is dependent on the oncogenic potential of the associated HPV type. HPV typing may provide a prognostic indicator for individual patients and is of potential use in defining specific therapies against HPV-harboring tumor cells.
From January 1, 1983 to December 31, 1990 two hundred and six patients with an invasive, non metastatic endometrial carcinoma were first treated at Institut Curie. Initial tumoral staging (TNM) was as follows: stage Ia: 48%, stage Ib: 31%, stage II: 15% and stage III-IV: 6%. Total hysterectomy or colpohysterectomy was performed in 186 cases, with a bilateral oophorectomy in 180 cases. Bilateral limited pelvic lymphadenectomy was performed in 116 cases. Brachytherapy was performed in the pre-operative setting in 25 cases, in the post-operative setting in 134 cases. Only five patients had brachytherapy alone, because of poor medical condition. External irradiation was exclusive in 15 cases and added to surgery for 68 patients. Median follow-up is 61 months (8-122 months). Five-year survival rate is 77% (71-83%); 5-year specific survival rate is 81% (75-87%). Independent prognostic factors for survival in multivariate analysis (Cox regression model) are tumoral stage (p < 0.0001), ovarian involvement (p < 0.0001), histologic node involvement (p = 0.005) and grade (p = 0.01). For local relapse, independent risk factors in the same analysis are ovarian involvement (p = 0.0004), tumoral stage (p = 0.01), age (p = 0.02) and histologic involvement of cervix (p = 0.04). For distant failure, independent risk factors are histologic node involvement (p = 0.0001), tumoral stage (p = 0.002) and grade (p = 0.003).
Having carried out four cases of vaginal caesarean section the authors describe the technique they used. The advantages of the operation are: it is simple and can be carried out quickly, future obstetric behaviour is not compromised. It is important to avoid two complications of the operation: haemorrhage and injury to the bladder. These are reduced if the vertical incision in the cervix is made in the midline and long enough. The ideal indications for the operation are absence of cervical dilatation, or the occurrence of severe maternal haemorrhage during the operation to terminate a pregnancy, or while the uterine contents are being expelled towards the end of the second trimester. It is disputable whether there is a place for vaginal caesarean operation when the fetus is alive, in view of the recent studies on fetal prognosis.