Biomedical subjects
J H Shepherd
Publications and source records attributed to J H Shepherd.
Measurement of urinary beta core fragment of human chorionic gonadotrophin in women with vulvovaginal malignancy and its prognostic significance.
Tumours of the vulva and vagina are rare and there are relatively few studies of circulating markers in these conditions. The urinary measurement of the core fragment of the beta-subunit of hCG has been proposed as a useful tumour marker in non-trophoblastic gynaecological malignancies. This study describe the measurement of urinary beta-core in 50 patients with vulvovaginal malignancy. In contrast to other studies corrections were made for both the effect of urine concentration and the age of the patient. Each patient was followed up for at least 24 months, and at this time their status was correlated with their initial level of urinary beta-core. The sensitivity of beta-core was only 38%, but of those patients with elevated levels 90% had died within 24 months, while only 32% of those with normal levels had died. For both patients at initial presentation and those with recurrent disease, there was a highly significant difference in the survival curve between those with elevated beta-core levels and those with normal levels. This is similar to findings in cervical carcinoma, and suggests that for lower genital tract cancer the measurement of urinary beta-core may be valuable as a prognostic indicator, allowing a more informed approach to treatment and follow-up.
Pelvic extenteration: a review of the Gateshead experience 1974-1992.
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Outpatient vulval biopsy--a note of caution.
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Ovarian cancers related to minimal access surgery.
OBJECTIVE: To review the clinical features of women with ovarian cancer on whom minimal access surgery has been performed and to determine guidelines for the safe use of minimal access surgery for adnexal masses. DESIGN: Postal survey of members of the British Gynaecological Cancer Society (BGCS) and retrospective case review. RESULTS: BGCS consultants used ultrasound scanning (70%) and serum CA-125 estimations (53%) prior to adnexal mass surgery. The membership felt that adnexal masses with solid elements, diameter greater than 8 cm, multi-ocular or bilateral cysts or increased blood flow on Doppler scanning should not be operated on by minimal access surgery. A positive family history was also considered to be a contraindication. A total of 29 cases of ovarian cancer were identified on whom MAS had been performed. The incidence of cases was 4.1% of referrals to a tertiary referral centre (the Royal Marsden Hospital). The median age of patients was 37 years (range 20 to 68 years) and 13 had State I cancers. The mean delay between diagnosis and staging was 6.5 weeks. CONCLUSION: Guidelines on the use of minimal access surgery in the management of adnexal masses need to be agreed. Women who have an ovarian cancer diagnosed whilst having minimal access surgery should have an accepted staging procedure. We do not recommend the routine use of minimal access surgery for the treatment of ovarian cancer outside a trial.
Psychosexual implications of gynaecological cancer.
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The prognostic significance of urinary beta core fragment in premenopausal women with carcinoma of the cervix.
The mortality of premenopausal women with cervical carcinoma has increased in recent decades despite attempts to provide screening. The urinary concentration of the beta core fragment of hCG has been proposed as a sensitive marker in gynecological malignancies, although most studies have not corrected for urine concentration. We measured the urinary concentration of beta core and creatinine in 61 women who developed cervical cancer premenopausally and expressed the concentration of beta core per millimole of creatinine using the 90th percentile of a control group as a cutoff level. While correcting for urinary concentration results in a reduction in sensitivity of the test (67 to 51%), there is improved correlation with prognosis in that after 18 months 81% of women positive for beta core had died, while 80% of women negative for beta core were still alive. Of those initially presenting and dying there was an increase with increasing stage of disease. For patients with initial presentation disease, 11 (79%) of the 14 patients with elevated levels had died compared with 1 of 21 (5%) who were negative for beta core. Urinary beta core fragment may have a major role as a prognostic indicator in cervical carcinoma rather than as a screening or diagnostic marker and enables identification of patients at higher risk of an aggressive disease.
Peroperative radioimmunodetection of ovarian carcinoma using a hand-held gamma detection probe.
Radioimmunoscintigraphy (RIS) can be used in the preoperative localisation of ovarian carcinoma to demonstrate uptake of radiolabelled monoclonal antibodies into neoplastic tissue. The tissue uptake of radiotracer was evaluated at laparotomy in 16 patients with suspected ovarian cancer who had preoperative RIS using technetium-99m-labelled monoclonal antibodies SM3 and H17E2. A gamma detection probe (gamma DP) was used to measure uptake in possible tumour deposits at operation and also the uptake in tissues resected for histology. The percentage uptake of the initial injected dose of radiotracer was also measured in resected tissues. Activity was found to be significantly higher in malignant than in non-neoplastic tissue by all three methods of evaluation. The gamma DP used peroperatively yielded a 82% sensitivity with a 72% specificity for an uptake ratio of 1.5:1. When tissue was examined immediately after resection, for a 100% specificity the sensitivity was 64%. In vitro measurements of monoclonal antibody uptake by tissue similarly gave a 65% sensitivity with a 100% specificity. Peroperative and immediate post-operative measurements of tissue radioactivity can be performed quickly and conveniently, and in some cases may be of benefit in the localisation of tumour at laparotomy and in providing extra information when tissue is examined by frozen section.
Multicentric carcinoma of the genital tract.
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Wound recurrence by implantation of a borderline ovarian tumour following laparoscopic removal.
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Expression of c-erbB-2, c-myc, and c-ras oncoproteins, insulin-like growth factor receptor I, and epidermal growth factor receptor in ovarian carcinoma.
AIMS: To assess whether the overexpression of five dominant oncogene encoded proteins is crucial to the pathogenesis of ovarian carcinoma and whether this provides any useful prognostic information. METHODS: The expression of the insulin-like growth factor 1 receptor (ILGFR 1), epidermal growth factor receptor (EGFR), and the c-erbB-2, c-ras, and c-myc products was studied by multiparameter flow cytometry in 80 patients with epithelial ovarian cancer for whom long term follow up was available. RESULTS: Overexpression of ILGFR 1, EGFR, c-erbB-2, c-ras and c-myc was found in, respectively, nine of 80 (11%), 10 of 80 (12%), 19 of 80 (24%), 16 of 80 (20%) and 28 of 80 (35%) ovarian carcinomas. The levels of expression of ILGFR 1, EGFR, c-erbB-2 and c-ras were significantly higher in the tumours of patients with recurrent or persistent disease after chemotherapy than in the tumours of patients at initial presentation (p < 0.02). Multivariate analysis showed that residual tumour (p < 0.001), FIGO stage (p = 0.002), EGFR overexpression (p = 0.030) and previous chemotherapy (p = 0.034) were independent variables for predicting survival. CONCLUSIONS: Overexpression of these oncoproteins only occurs in a small proportion of ovarian carcinomas but may have an important role in the progression of the disease.
Serum placental-type alkaline phosphatase activity in women with squamous and glandular malignancies of the reproductive tract.
AIM: To investigate serum placental-type alkaline phosphatase (PLAP-type) activities in women with squamous and glandular malignancies of the reproductive tract using an immunoradiometric assay. METHODS: PLAP-type immunoreactivity was measured in 180 women with non-ovarian malignancies of the reproductive tract and the values were compared with those from 334 controls. The cases comprised 18 vulval, nine vaginal, 103 cervical, 46 endometrial, and five fallopian tube cancers. RESULTS: Serum PLAP-type activities were no different from controls in patients with squamous cell tumours. Women with adenocarcinoma of the cervix, endometrium, and fallopian tube had increased values: women with endometrial cancer had a median value nearly four times greater than that of controls. There was no direct correlation between PLAP-type activities and stage of disease in patients with endometrial cancer, but values reverted to normal after treatment. CONCLUSIONS: Serum PLAP-type measurements are of no value in the management of patients with squamous cell tumours of the female reproductive tract. Raised activities can, however, be found in glandular tumours, in particular endometrial cancer where serum PLAP-type measurements may be of value in predicting remission.
Diurnal variation of urinary "hCG beta subunit core fragment" production evaluated in patients with gynecological neoplasms.
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Reconstructive procedures in benign and malignant gynecological surgery.
The management of female cancers may involve radical surgery and radiotherapy, which results in damage to or loss of the pelvic organs and female genitalia. New procedures have been developed and applied in gynecological oncology, allowing reconstruction of continent bladders, of new vaginas (both for cosmesis and function), and preserving fecal continence. The use of a range of plastic procedures have enabled the restoration of the external appearances, which leads to improved recovery and a better quality of life.
Urinary chorionic gonadotropin subunits and beta-core in nonpregnant women. A study of benign and malignant gynecologic disorders.
BACKGROUND: The presence of urinary excretion products of human chorionic gonadotropin (hCG) has been proposed as a tumor marker. To ascertain the clinical value in gynecologic cancers, the authors studied 612 nonpregnant women. METHODS: Three different assays in four clinical groups were compared: no disease, benign disease, malignant disease, and complete remission of previously treated malignant disease. The assays were for the urinary beta-core, "total" beta-hCG, and free alpha-subunit. RESULTS: Measurement of the alpha-subunit was of no obvious clinical value. In some patients with benign disease, hCG metabolites were elevated. In the 141 patients with active gynecologic malignancy the sensitivity of the total beta-hCG assay was 47% and that of the beta-core assay was 36%. The specificities were 80.3% and 90.4%, respectively. Advanced cancers generally had higher levels of total beta-hCG and beta-core. Squamous cell and poorly differentiated cervical tumors had higher levels of total beta-hCG than did adenocarcinomas and well-differentiated cervical tumors. Invasive, serous, endometrioid, and germ cell ovarian tumors had higher total beta-hCG, beta-core, and alpha-subunit levels than did borderline, mucinous, and clear cell ovarian tumors. Six of 16 patients with disease in complete remission had elevated levels. CONCLUSION: The excretion of hCG and its metabolic fragments is a common event in gynecologic cancer, but sensitivity and specificity are low, and there is little consistent relationship between tumor stage and histologic type.
Reconstruction of the abdominal wall with a latissimus dorsi musculocutaneous flap: a case of a massive abdominal wall metastasis from a cervical cancer requiring palliative resection.
A 49-year-old woman presented with a huge abdominal mass. At laparotomy, a 36-cm diameter semisolid, semicystic mass from the abdominal wall was removed. The peritoneal defect was covered by a mesh and a free latissimus dorsi myocutaneous flap. Histology showed a poorly differentiated squamous cell carcinoma consistent with metastatic tumor from a cervical primary. Surgery has a finite palliative role to extirpate a tumor mass of this size if reconstruction and some form of closure can be achieved.
The measurement of urinary beta core fragment in conjunction with serum CA125 does not aid the differentiation of malignant from benign pelvic masses.
The urinary concentration of the renal metabolite of the beta subunit of human chorionic gonadotropin (beta core) has been proposed as a tumor marker in certain nontrophoblastic malignancies including those of the female genital tract. A previous study investigated the use of urinary beta core in conjunction with serum CA125 in distinguishing malignant from benign pelvic masses and showed that the combined test improved the overall sensitivity to 88%; this was greater than that for either test alone. However, the cutoff levels used to distinguish normal from abnormal were approximately six times greater than those generally used for CA125 and four to five times lower than those used for beta core in our laboratory. Furthermore there was no recognition of the possible difference in normal levels of beta core between pre- and postmenopausal women. We have examined a similar group of cases using our cutoff levels for urinary beta core of 0.36 ng/ml in premenopausal women and 0.48 ng/ml in postmenopausal women and 35 u/ml for CA125. We show that measurement of CA125 is substantially more sensitive that that of beta core and that the combination of beta core with CA125 does not improve the overall sensitivity of the test. However, there was a small improvement in positive predictive value if both tests were positive (97.5%) and of specificity when one or the other test was negative (98.5%).
Zollinger-Ellison syndrome caused by a mucinous cystadenocarcinoma of the ovary.
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