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Biomedical subjects

J H Shepherd

Publications and source records attributed to J H Shepherd.

At least 91 records · Page 5Linked to original sources

Multi-parameter flow cytometric quantitation of the expression of the tumor-associated antigen SM3 in normal and neoplastic ovarian tissues. A comparison with HMFG1 and HMFG2.

SM3 is a monoclonal antibody that reacts with a peptide epitope in the core protein of polymorphic epithelial mucin. Multi-parameter flow cytometry was used to characterize the expression of SM3 and compare it with two related tumor-associated antigens, HMFG1 and HMFG2, in cell suspensions of 44 malignant ovarian tumors, 15 benign ovarian tumors, and 16 normal ovaries. Tumor-associated antigen expression was significantly higher in malignant ovarian neoplasms than in benign neoplasms (P less than 0.001 for all three antigens). SM3 was expressed more specifically in malignant than benign tumors but had a lower affinity than HMFG1 and HMFG2. Multi-parameter flow cytometric evaluation of a panel of monoclonal antibodies can be used to help in choosing the best antibody for immunohistochemistry, imaging, and eventually treatment of ovarian tumors.

Antibodies, Monoclonal↗

Sonographic depiction of postmenopausal endometrium with transabdominal and transvaginal scanning.

The thickness of the endometrium was measured in postmenopausal women by both the transvaginal and transabdominal ultrasound approaches in two separate groups of patients. The first group consisted of 90 women who received a transabdominal scan of the endometrium before dilatation and curettage or hysterectomy for either postmenopausal bleeding or uterine prolapse. The second group consisted of 111 women who underwent a transvaginal scan of the endometrium for similar postmenopausal conditions. Both methods suggested that an endometrial thickness of 5 mm may be used as a cut-off level in the conservative management of patients with postmenopausal bleeding or in a screening program for endometrial carcinoma. Patient acceptance and image quality were better in the group examined transvaginally. The proximity of the transvaginal probe to the endometrium, in the absence of a full bladder compressing the endometrium, revealed a unique group of patients with atrophic endometrium but thick endometrial cavity caused by intracavity fluid. In the presence of uterine fibroids distorting the uterine cavity, transvaginal scanning was better than transabdominal scanning for visualizing the endometrium. The transabdominal full-bladder technique can be of value in detecting asymptomatic bladder pathology.

Journal Article↗

Hormone replacement therapy and survival after surgery for ovarian cancer.

OBJECTIVE: To evaluate whether hormone replacement therapy affects survival in women who have undergone bilateral salphingo-oophorectomy because of epithelial ovarian cancer. DESIGN: Retrospective analysis by review of patients' notes and questionnaires completed by general practitioners to compare the overall survival and disease free survival in patients with ovarian cancer who did or did not receive hormone replacement therapy after diagnosis. Data were analysed by Cox regression, with hormone replacement therapy as a time dependent covariate because patients who received hormone replacement did so at different times after diagnosis. SETTING: Gynaecological oncology unit of Royal Marsden Hospital. PATIENTS: 373 patients aged 50 years or younger who attended the hospital from 1972 to 1988. All of the women had undergone bilateral salpingoophorectomy for epithelial ovarian cancer. In all, 78 had received hormone replacement therapy, starting at a median of four months after diagnosis. INTERVENTION: A questionnaire was sent to the general practitioners of all patients who were not recorded as having received hormone replacement therapy. MAIN OUTCOME MEASURES: Overall survival and disease free survival. RESULTS: There was no significant difference in survival between women receiving hormone replacement therapy and those not receiving it after accounting for the effects of other known prognostic factors (stage of cancer, differentiation of tumour, histological results, and time to relapse). The relative risk of dying in those who received hormone replacement therapy was 0.73 (95% confidence interval 0.44 to 1.20). In addition, there was no significant difference in disease free survival (relative risk in those receiving hormone replacement therapy was 0.90; 95% confidence interval 0.52 to 1.54). CONCLUSIONS: This study shows that hormone replacement therapy is unlikely to have a detrimental effect on the prognosis of patients with ovarian cancer, but this would be shown conclusively only by a randomised controlled trial.

Adult↗

Multiparameter flow-cytometric quantitation of epidermal growth factor receptor and c-erbB-2 oncoprotein in normal and neoplastic tissues of the female genital tract.

A novel multiparameter flow-cytometric method was used to quantify the expression of epidermal growth factor receptor (EGFR) and c-erbB-2 oncoprotein on 85 cryopreserved normal tissues (30 ovary, 29 endometrium, 16 cervix) and 67 carcinomas (31 ovarian, 18 cervical, 15 endometrial, 3 vulvar). Overexpression of the EGFR and c-erbB-2 oncoproteins was found in respectively 3/31 (9%) and 10/31 (32%) ovarian carcinomas, 13/18 (72%) and 7/18 (38%) cervical carcinomas, and 2/15 (13%) and 2/15 (13%) endometrial carcinomas. Oncoprotein expression was significantly higher in the malignant tumors (for all tumor sites) than in the corresponding normal tissues (P less than 0.034 for all combinations). Aneuploid tumors expressed levels of EGFR and c-erbB-2 oncoprotein significantly higher than those of DNA diploid tumors (P = 0.042 and P = 0.048, respectively). Oncoprotein could be detected in nearly all normal tissues: expression was higher in premenopausal than in postmenopausal patients (EGFR, P = 0.07; c-erbB-2, P less than 0.001). The present study supports the idea that EGFR and c-erbB-2 may play an important role in the autocrine, paracrine, and/or endocrine growth control and differentiation of normal tissues. Alteration in the expression of these oncoproteins is probably involved in malignant transformation and tumorigenesis.

Carcinoma↗

Williams' vulvovaginoplasty after supralevator total pelvic exenteration.

Seven patients had delayed Williams' vulvovaginoplasty after supralevator total pelvic exenteration. Of the three patients who died of carcinoma of the cervix (at 2, 5, and 15 months after vulvovaginoplasty), the first died before having a chance to attempt intercourse, but the other two had reported intercourse on at least two occasions after the reconstruction. One of the patients described the experiences as neither pleasant nor unpleasant but stated that her husband seemed satisfied. The other patient described the experience as satisfactory to both herself and her husband. The remaining four patients are alive with no evidence of recurrent disease at 28, 42, 56, and 106 months after operation. Two of these patients have reported entirely satisfactory sexual relations approximating pre-exenteration frequency, but the remaining two have not had sexual relations since surgery. Both give the main reason for this as lack of opportunity. The Williams' vulvovaginoplasty appears to be a reasonable alternative for vaginal reconstruction in patients who will have and especially who have had exenteration. To improve results, other methods of vaginal reconstruction should continue to be evaluated.

Adult↗

The role of vaginal scan in measurement of endometrial thickness in postmenopausal women.

Transvaginal ultrasound scanning was performed on 111 postmenopausal women. Of these women, 103 had postmenopausal bleeding, and eight were undergoing hysterectomy. Of the 103 women with bleeding, 93 had dilatation and curettage (D&C) and 10 patients were treated conservatively with a repeat scan in six months. A correlation of ultrasound findings and endometrial histopathology was possible in 94 patients. In 59 of these (63%) the endometrium was atrophic and the ultrasound endometrial thickness was 5 mm or less. In 29 (31%) patients the endometrial histology was abnormal and ultrasound endometrial thickness was greater than 5 mm. In six patients the endometrium was atrophic, but the ultrasonic endometrial thickness was apparently greater than 5 mm due to intracavity fluid. We suggest that an endometrial thickness of 5 mm is an appropriate cut-off level for conservative management of patients with postmenopausal bleeding, or in screening for endometrial carcinoma.

Aged↗

Anterior pelvic reconstruction with ileum after cancer treatment.

Ileum has been used to reconstruct the lower urinary tract in 15 patients (10 women, five men) after treatment for bladder or gynaecological cancer. Seven patients had previously received radical pelvic irradiation. Four methods were used: group 1 (five patients): bladder patch after partial cystectomy or bladder augmentation after clam cystotomy for bladder contracture; group 2 (four patients): bladder replacement after subtotal (supratrigonal) cystectomy; group 3 (two patients): ureteric replacement for lower ureteric obstruction or fistula, and group 4 (four patients): complete replacement of bladder and lower ureters after anterior pelvic exenteration, with creation of neovagina from caecum in the two female patients. Review of the results indicates that ileum provides a versatile and safe material for anterior pelvic reconstruction in cancer patients even after previous pelvic irradiation.

Adult↗

The purification and development of a radioimmunoassay for beta-core fragment of human chorionic gonadotrophin in urine: application as a marker of gynaecological cancer in premenopausal and postmenopausal women.

The beta-core fragment of human chorionic gonadotrophin (hCG) is a major part of the immunoreactive hCG-like material found in the urine of normal pregnant women. Patients with non-trophoblastic gynaecological malignancies have been found to have raised levels of urinary beta-core. We describe the purification of beta-core, the preparation of a polyclonal sheep antiserum and the development of radioimmunoassay. The minimum detection limit of this assay was 0.025 micrograms beta-core/l. There was no significant cross-reaction with the free alpha-subunit, hLH, hFSH and hTSH (less than 0.7%), and only partial cross-reaction with intact hCG and free beta-subunit of hCG (6.9 and 18%). Within-assay variability ranged from 2.03 to 12.5% and between-assay variability from 2.25 to 13.4%. The assay was applied to urine samples from 92 normal non-pregnant premenopausal women, 54 normal postmenopausal women and 65 women with active gynaecological disease (47 postmenopausal and 18 premenopausal). In normal premenopausal women the values ranged from less than 0.025 to 0.62 micrograms beta-core/l (median 0.043 micrograms beta-core/l). The values for normal postmenopausal women ranged from less than 0.025 to 0.64 micrograms beta-core/l (median 0.26 micrograms beta-core/l). Postmenopausal women with gynaecological malignancy had values which ranged from less than 0.025 to 4.0 micrograms/beta-core/l (median 0.31 micrograms beta-core/l); premenopausal women in this group had values which ranged from less than 0.025 to 1.15 micrograms beta-core/l (median 0.12 micrograms beta-core/l). On molecular sieve chromatography, the material found in the urine of normal postmenopausal women showed the physicochemical characteristics of authentic beta-core.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Radioimmunoscintigraphy of ovarian tumors using a new monoclonal antibody, SM-3.

Radioimmunoscintigraphy with SM-3 monoclonal antibody produces results similar to those obtained with 123I-labeled HMFG-2. The tumor specificity of SM-3 in vitro is not as marked as that in vivo. SM-3 is, however, much easier to produce in tissue culture and, with the availability of 99mTc labelling, has allowed radioimmunoscintigraphy to be done as an outpatient procedure. This technique has important implications for the continuing management of patients with ovarian cancer.

Adult↗

Retroperitoneal soft tissue sarcomas: a review of the literature.

The English language literature on retroperitoneal sarcomas published between 1981 and 1988 has been reviewed. The histology, different prognostic factors, value of imaging techniques, and need for multidisciplinary management are discussed. Complete surgical excision with tumor-free margins confirmed by histology is essential if long-term survival and local control are to be achieved. In many cases resection of adjacent organs is required as most patients present with advanced, aggressive local disease. The roles of adjuvant radiotherapy and chemotherapy in the treatment of retroperitoneal sarcomas are uncertain and must await further controlled, randomized, prospective studies.

Diagnosis, Differential↗

A pilot study of chemo-radiotherapy in advanced carcinoma of the vulva.

Advanced squamous cell carcinoma of the vulva (FIGO stages III and IV) has a poor cure rate even with exenterative surgery. We report a pilot study of combined pre-operative chemo-radiotherapy (CHT/RT) in all patients with advanced vulval carcinoma presenting to St Bartholomew's Hospital between July 1987 and March 1989. Twelve patients have been treated, of whom nine had primary lesions (four FIGO stage III and five stage IV) and three had recurrent disease after simple or radical vulvectomy. Seven patients were treated with an initial split course of CHT/RT: there was one treatment-related death and the others have all died following recurrence with a median disease-free survival of 5 months (range 3-12) and a median survival of 7 months (range 3-16). Five patients have received a continuous course of CHT/RT: one died before operation with pulmonary metastases, three patients are disease free at 6 to 9 months, and another patient has been treated with only palliative intent. Toxicity was acceptable in the continuous regimen and this treatment seems to have a promising role in the management of advanced carcinoma of the vulva. A review of the literature on combined therapy is presented.

Aged↗

The use of rectus abdominis myocutaneous flaps following excision of vulvar cancer.

Rectus abdominis myocutaneous flaps have been used in 16 women following radical excision of extensive vulvar cancer. In two women the procedure was part of the primary surgery, in 11 for recurrence of vulvar cancer and in three for symptomatic palliation. Fifteen (94%) of the grafts took with primary healing. Thirteen of the 16 patients are alive 6-60 months (median 29 months) after surgery and the three who died benefited from symptomatic palliation. Simultaneous vulvar reconstruction allows good cosmetic rehabilitation and is an important part of the armamentarium for the management of patients with advanced primary or recurrent vulvar carcinoma. This technique offers excellent surgical clearance of massive offensive and painful vulvar tumors.

Adult↗

Tissue preparation for simultaneous flow cytometric quantitation of tumour associated antigens and DNA in solid tumours.

A multiparameter flow cytometric assay for the simultaneous study of tumour associated antigens (TAA) and DNA in fresh solid tumours was devised. Cell suspensions were prepared by disaggregating unfixed solid tumour samples mechanically over a stainless steel mesh. Indirect immunofluorescence was used to identify the TAA, and DNA was stained with propidium iodide. Cell morphology was well preserved, cell clumping was negligible, and high quality indirect immunofluorescence quality indirect immunofluorescence and DNA staining were obtained. The technique is simple, rapid, and reproducible. Multiparameter assays can be developed to study prognostic indicators such as membrane oncoproteins, receptors, and multidrug resistance in solid tumours. With a suitable panel of antibodies the technique might become an aid in the differential diagnosis and biochemical diagnosis of some solid tumours.

Antigens, Tumor-Associated, Carbohydrate↗

Therapeutic considerations in the use of intraperitoneal radiolabelled monoclonal antibodies in ovarian carcinoma.

Eleven patients with ovarian cancer have been treated with a radiolabelled monoclonal antibody directed against human milk fat globule membrane (HMFG2). All patients had Stage III disease and had previously undergone debulking surgery followed by chemotherapy. Although 16 patients have been referred, 5 could not be treated. This paper discusses the criteria for patient selection and treatment, and describes the technical difficulties of this form of therapy and the complications sustained following the intraperitoneal instillation of up to 150 mCi iodine-131 labelled HMFG2. Significant complications included two ileo-cutaneous fistulae and peritonitis in one patient which prevented treatment from being given.

Adult↗