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Biomedical subjects

C Fisher

Publications and source records attributed to C Fisher.

At least 19 recordsLinked to original sources

Detection of premature atherosclerosis by high-resolution ultrasonography in symptom-free hypopituitary adults.

Retrospective analysis suggests that there is increased mortality from vascular disease in hypopituitary adults, but vascular status before death is unknown. High resolution B-mode ultrasonic imaging of both carotid and femoral arteries was therefore done in 34 adult hypopituitary patients on routine replacement therapy and was compared with that in 39 matched controls. Changes were related to risk factors for vascular disease. Carotid intima-media thickness was greater in patients than in controls (mean [SD] 0.74 [0.16] vs 0.65 [0.13] mm, p < 0.02). This difference was seen in middle-aged and elderly patients. More patients than controls had one or more atheromatous plaques (65% vs 41%, p < 0.05). The percentage of individual arteries with a plaque was also higher in patients (32% vs 18%, p < 0.005). In multiple regression analysis, patients' age was the dominant factor determining carotid intima-media thickness. Symptom-free adults with hypopituitarism show an increased prevalence of atherosclerosis.

Adult

Ifosfamide is an active drug for chemotherapy of metastatic cystosarcoma phyllodes.

Metastases from cystosarcoma phyllodes are rare, and treatment generally is ineffective. Four patients were treated with ifosfamide (alone in three and combined with doxorubicin in one). Two patients had complete remissions that lasted 26 and 61+ months. One other patient had a partial response that lasted 13 months. The complete responders were both treated as soon as metastases appeared, when they had only a small volume of disease. This appears to represent a significant improvement on other described regimens for this condition, and further trials of ifosfamide are warranted. Close follow-up of patients at high risk for metastases is suggested.

Adult

The clinical and histologic criteria that predict metastases from cystosarcoma phyllodes.

A retrospective study of 33 patients with cystosarcoma phyllodes was done. Eight of these patients had metastases, and the clinical and histologic criteria predicting the development of metastases were examined. The most reliable predictor was the presence of stromal overgrowth; this appears to be necessary for metastasis to occur. Other useful indicators of clinical behavior were the degree of mitotic activity, nuclear pleomorphism, and infiltrating margins. Based on these data and a literature review, the authors suggest close follow-up of patients whose primary tumors contain areas of stromal overgrowth because, in all series combined, the risk of metastatic spread in such patients was 72% within 5 years. Among these high-risk patients, local recurrence is another indication that metastasis is likely.

Adolescent

Carcinoma in episiotomy scars.

The finding of primary or metastatic carcinoma in an episiotomy scar is a rare event; we report three cases. The first patient presented with an abnormal cervical smear and was found to have a primary squamous cell carcinoma of the vulva in an old, healed episiotomy scar. A second patient, diagnosed as having cervical carcinoma 6 months postpartum, was found to have a metastatic deposit in the episiotomy scar during the staging of her disease. The third patient developed adenocarcinoma metastatic from an endocervical primary in an episiotomy scar that presented as a small nodule at the introitus. These cases exemplify the need for careful inspection and biopsy of any nodular lesions in episiotomy scars as part of the initial assessment and follow-up of patients with premalignant or malignant lesions of the lower genital tract.

Adult

Benign mimics of soft tissue sarcomas.

We reviewed all new patients referred for treatment to the Sarcoma Unit at the Royal Marsden Hospital with a clinical diagnosis of soft tissue sarcoma (STS) during the course of 1 year (1989-1990). Of 118 patients, 65 (55.1%) had primary STS, 26 (22.0%) had recurrent STS, 19 (16.1%) had benign soft tissue tumours and eight (6.8%) had malignant tumours other than STS involving soft tissues and presenting clinically as soft tissue tumours. All patients underwent CT scanning which was used to assist diagnosis, assess operability or for radiotherapy planning. The CT findings of the benign lesions, all clinically suspicious of sarcoma, are discussed. The role of CT in the identification and management of these cases is emphasized.

Arteriovenous Malformations

Preoperative radiotherapy for initially inoperable extremity soft tissue sarcomas.

The results and complications of a combination of preoperative radiotherapy and surgery in the treatment of 70 patients with large or fixed extremity soft tissue sarcomas are reported. Sixty-one patients were referred with a primary tumour and 9 had recurrences. Thirty-three patients had tumours in the thigh and 38 tumours were fixed to neighbouring structures. The mean preoperative dose was 53 Gy (range 21-75). Eleven patients received a postoperative boost to tumour site. Four patients received preoperative intra-arterial Adriamycin. Overall, 42 patients (60%) responded to the radiotherapy, 4 with complete tumour resolution. Eighty per cent of those receiving greater than or equal to 60 Gy responded and a significant correlation between 2 Gy equivalent dose and response was demonstrated (P less than 0.005). The degree of tumour necrosis was increased in 23 of 52 evaluable patients following radiotherapy, although there was no correlation with dose or clinical response. There have been eight local recurrences and 17 deaths after a median follow-up of 2 years. Tumour size less than 10 cm was the only significant factor in the development of local recurrence (P = 0.04). Thirty-six patients developed immediate postoperative complications: 9 major (13%), 13 moderate (19%) and 14 minor (20%). Increasing patient age was the only significant independent factor for the development of complications (P = 0.015). Preoperative radiotherapy will usually permit limb conservation of extremity sarcomas which otherwise would be inoperable or require amputation. However, the increased incidence of wound complications in older patients demands meticulous technique.

Adolescent

Popliteal vein entrapment in the normal population.

The aim of this study was to determine the incidence and severity of popliteal vein compression by full knee extension in the normal population. The popliteal veins in 100 healthy volunteers (200 limbs) with no history of previous deep vein thrombosis (DVT) or venous obstruction were examined using duplex scanning with the knee slightly flexed and then fully extended. Knee extension produced complete obstruction in 17 subjects and severe obstruction (< 50% decrease in diameter) in a further 10 subjects. Thirteen subjects had unilateral compression and 14 bilateral. The 27 subjects were tested for functional venous outflow obstruction with air plethysmography. In flexion, the outflow fraction was normal (> 40%) in all subjects. With the knee fully extended, severe or complete venous obstruction (outflow fraction < 10%) was found in eight subjects. Moderate obstruction (outflow fraction 10-40%) was found in all the remaining 19 subjects. When digital compression of the long saphenous vein was performed, these subjects also demonstrated severe outflow obstruction. Although the incidence of symptoms of functional venous obstruction is rare in the general population, these findings have important implications for venous stasis for patients on the operating table and in those having prolonged bed rest. Studies investigating the association between popliteal vein compression and postoperative deep venous thrombosis are needed.

Adult

The role of electron microscopy in the diagnosis of tumours of the head and neck.

A four-year study was undertaken to determine the value of electron microscopy in the diagnosis of head and neck tumours. During this period 80 samples were submitted for examination, of which 69 contained assessable tumour. Electron microscopy made a major contribution to the diagnosis in 25 cases (36 per cent). Areas in which ultrastructural examination was of diagnostic significance included the precise categorization of apparently undifferentiated carcinoma and the identification of melanomas. Little diagnostic benefit was gained from electron microscopic examination of thyroid, lymphoid or salivary gland neoplasms. The value of electron microscopy in relation to immunohistochemistry is discussed.

Carcinoma, Squamous Cell

Surveillance following orchidectomy for stage I testicular seminoma.

An analysis of the primary tumour histopathology was performed on 103 patients managed by orchidectomy and surveillance for stage I seminoma. Patients have been followed for 14-141 months (median 62 months) after orchidectomy. Seventeen patients relapsed, the probability of remaining relapse free at 5 years being 82% (95% confidence intervals, 74%-88%). No patients died of progressive germ cell tumours. The only significant histological factor predicting relapse was the presence of lymphatic and vascular invasion. Four of 42 patients with neither lymphatic or vascular invasion recurred, nine of 53 patients with either lymphatic or vascular invasion recurred and three of eight cases with both lymphatic and vascular invasion recurred (P = 0.05-trend). Though initial recurrence was usually of moderate volume and confined to para-aortic nodes, eight patients were treated with chemotherapy either because of the extent of their initial relapse (four cases), or because of subsequent relapse (four cases). In view of the difficulties of identifying patients at risk and of detecting early relapse, surveillance for stage I seminoma should remain a research protocol.

Adult

Angiomyofibroblastoma of the vulva. A benign neoplasm distinct from aggressive angiomyxoma.

Aggressive angiomyxoma of pelvic soft parts is a rare lesion with a high risk of recurrence. We report 10 cases of angiomyofibroblastoma, a hitherto uncharacterized benign tumor of the vulva histologically mimicking aggressive angiomyxoma. All patients had a vulval mass, often clinically diagnosed as a Bartholin's cyst. There was no recurrence after excision. The tumors were well circumscribed, measuring 0.5-12 cm in maximum dimension. They were characterized by alternating hypercellular and hypocellular edematous zones in which abundant blood vessels (predominantly of the capillary type) were irregularly distributed. Spindled, plump spindled, and oval stromal cells were aggregated around the blood vessels, sometimes forming solid compact foci, or were loosely dispersed in the hypocellular areas. Their nuclei were bland, but rare ones were enlarged and hyperchromatic in four cases. Some cells had abundant eosinophilic hyaline cytoplasm and eccentrically placed nuclei. Mitotic figures were absent or very sparse. Scattered throughout were thin, wavy strands or thick bundles of collagen. Mast cells were readily seen in eight cases. Immunohistochemically, the stromal cells were reactive for vimentin and desmin, but not cytokeratin, muscle-specific actin, alpha-smooth muscle actin, or S-100 protein. Ultrastructural studies showed well-developed rough endoplasmic reticulum, Golgi apparatus, abundant intermediate filaments, and pinocytotic vesicles in the stromal cells. Angiomyofibroblastoma can be distinguished from aggressive angiomyxoma by its circumscribed borders, much higher cellularity, more numerous blood vessels (which lack prominent hyalinization), frequent presence of plump stromal cells, minimal stromal mucin, and rarity of erythrocyte extravasation.

Adult

Abnormalities of epidermal differentiation associated with expression of the human papillomavirus type 1 early region in transgenic mice.

The promoter region of a keratin 6 (K6) gene was used to regulate expression of the early region of human papillomavirus type 1 (HPV-1e) in transgenic mice. In one line of mice the K6-HPV1e transgene was transcribed in several regions of the skin, the predominant transcript being a 1.1 kb RNA including the E4 open reading frame, and E1-E4 protein was detected in the upper suprabasal layers of the skin in paws and tail. A 1.7 kb RNA corresponding to the E6/E7 transcript was also prominent in tails of homozygous transgenic animals. In young homozygous transgenic mice the epidermis of the tail showed dysplasia and hyperplasia of the suprabasal layers with both hyperkeratosis and focal parakeratosis in the stratum corneum. A similar though milder phenotype was also observed sporadically in hemizygous transgenics. Analysis of the pattern of mouse keratins present in the affected tail skin showed strong up-regulation of the endogenous keratins 6 and 16 throughout the basal and suprabasal layers, suggesting a positive feedback mechanism for the strong transgene activation. Expression of the major differentiation-specific keratins 1 and 10 was repressed. The pattern of E1-E4 expression and the perturbation of normal epithelial differentiation parallel many of the characteristics of HPV-1 warts or verrucae, suggesting that HPV transgenic mice could be useful for analysis of the interactions of HPV gene products with cellular regulatory pathways within an otherwise normal epithelium.

Animals

Chylous ascites in Kaposi's sarcoma: a case report.

We report a case of a patient with Kaposi's sarcoma (KS), massive chylous ascites and chylous pleural effusions. This association has not been reported previously. The pathogenesis of chylous effusions is discussed with respect to KS.

Chylous Ascites

Peripheral nerve sheath differentiation in malignant soft tissue tumours: an ultrastructural and immunohistochemical study.

Thirteen soft tissue sarcomas with ultrastructural evidence of nerve sheath differentiation were investigated by immunohistochemistry. Three arose in a major nerve or nerve trunk and four patients had von Recklinghausen's neurofibromatosis. Ultrastructurally, 10 cases showed variable differentiation towards Schwann cells, two resembled perineurial cells and one tumour had features suggestive of both cell types. Immunostaining for S-100 protein was positive in eight Schwann cell tumours, negative in the other two Schwann cell tumours and negative in those with perineurial-like cells. No cases demonstrated epithelial membrane antigen, so that the existence of perineurial cells in malignant nerve sheath tumours remains immunohistochemically unsubstantiated; it may be that the perineurial-like cells are merely incompletely differentiated Schwann cells, with nerve sheath differentiation manifesting a continuous spectrum. Leu 7 was detected in four Schwann cell tumours, three of which were ultrastructurally well differentiated. Cytokeratin and desmin were demonstrated only in an undifferentiated pleomorphic area of one Schwann cell tumour. Electronmicroscopy can aid diagnosis by revealing nerve sheath differentiation in malignant soft tissue tumours without demonstrable S-100 protein.

Adolescent

Proliferating cell nuclear antigen and S phase fraction in endometrial stromal sarcoma.

AIMS: To investigate the value of immunohistochemical staining for the cell cycle protein proliferating cell nuclear antigen (PCNA) and flow cytometric S phase fraction in determining prognosis in endometrial stromal sarcoma, graded according to mitotic count. METHODS: Seventeen endometrial stromal sarcomas from 13 patients treated at the Royal Marsden Hospital were analysed. Serial 5 microns sections were cut for haematoxylin and eosin and immunohistochemical staining for PCNA, performed using the murine monoclonal antibody PC10. PCNA positivity was expressed as a percentage of the total number of cells (PCNA index). Flow cytometric analysis was performed on nuclei extracted from paraffin wax sections. RESULTS: In the five patients who died of disease within five years, PCNA index varied between < 1% and 60% (mean 21%) and S phase fraction ranged from 11.3 and 20.1 (mean 13.8). Four patients who were apparently cured showed PCNA indices ranging from < 1% to 5% (mean 1.75%) and S phase fraction ranging from 1.4 to 3.5 (mean 2.3); and three patients alive with disease showed PCNA indices ranging from 1% to 15% (mean 8.6%) and S phase fraction ranging from 1.4 to 3.5 (mean 2.3). One patient who died from indolent local disease after nine years showed a PCNA of 1 or less and an S phase fraction of 0.9. CONCLUSIONS: PCNA staining was variable and therefore not a reliable prognostic indicator, but a high PCNA index was only found in those patients dying of disease within five years. A stronger association was seen between S phase fraction and prognosis; this also correlated well with histological grade determined by mitotic count. In individual borderline cases that are between low and high grade categories, these procedures may be useful.

Antigens, Neoplasm