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Biomedical subjects

J H Shepherd

Publications and source records attributed to J H Shepherd.

At least 109 records · Page 6Linked to original sources

Pelvic exenteration. Has it a role in 1987? A six year experience.

Pelvic exenteration entails extensive radical surgery with evisceration of pelvic organs involved with central recurrence of pelvic cancer. It may occasionally be indicated as a primary surgical procedure. A tumour arising from any pelvic organ may require this surgery but those from the cervix and vulva primarily are particularly amenable to such surgery. Certain ovarian tumours with involvement of the rectum and large pelvic masses not responsive to previous surgery or chemotherapy may also be considered for exenterative type surgery as a type of salvage operation. Strict criteria must be observed to exclude either distal spread or local fixation in the pelvis with consequent lymphatic or vascular involvement. For patients with recurrent cervical cancer, 50% of those referred were rejected at examination under anaesthetic as being inoperable: 20% overall were surgically suitable for the procedure at exploratory laparotomy. The final decision to proceed is made at laparotomy with frozen section assessments to ensure adequate clearance of tumour. Urinary diversion by means of an ileal conduit and also terminal colostomy will be required after total pelvic exenteration. Anterior or posterior exenteration will require diversion only of either the urinary or gastrointestinal tract. Large vulvar tumours may require simultaneous musculocutaneous flaps in order to obtain adequate closure of large defects with satisfactory skin coverage. 52 such procedures have been performed over the last five years. 25 of these have been for extensive ovarian carcinomas as a salvage procedure following previous failed surgery and chemotherapy. A median survival of two years six months as opposed to 10 months in an inoperable but comparable group was obtained. 12 patients with recurrent cervical cancer and 8 with advanced vulvar cancer were also operated on. The mean age was 59 years with a range of 30-76 years. The operative mortality following this extensive and radical procedure was 6% with 3 deaths occurring at 24 hours, one month and three months post surgery. A 20% morbidity occurred with varied complications including haemorrhage (3 patients) and fistulae (2 patients). The overall survival at 3 years was 48% with 75% survival for patients with carcinoma of the vulva and 60% with carcinoma of the cervix. No patients with involved lymphadenopathy survived. With a combined team approach to the careful selection and management of suitable cases, a 50% five year survival may be obtained with patients undergoing pelvic exenteration for advanced pelvic cancer.

Adult↗

Carcinoma in situ of the vulva: 24 years' experience in southwest Florida.

We retrospectively studied 125 patients treated for carcinoma in situ of the vulva from 1961 through 1984, with follow-up ranging from one to 24 years. Patients' ages ranged from 24 to 90 years, with a mean age of 53 years. Multifocal disease was more common in women under age 40. Pruritus was the most common complaint, but 60% of the patients were asymptomatic. Twenty-five patients (20%) had other associated malignancies: carcinoma in situ of the cervix in ten patients, invasive carcinoma of the cervix in six, multifocal carcinoma in situ involving vulva, vagina, and cervix in five, vaginal carcinoma in situ in two, and endometrial carcinoma in two. Sixty-five patients were treated primarily with wide excision, 45 with total vulvectomy, seven with "subtotal" vulvectomy, three with skinning vulvectomy, and three with vulvectomy and bilateral groin node dissection; two patients refused treatment. Fifteen patients had a recurrence--recurrent carcinoma in situ in ten, and invasive carcinoma of the vulva in five. Whether the patient had had total vulvectomy or a lesser procedure appeared to make no difference in the recurrence rate. Thus a well planned excision of vulvar carcinoma in situ appears to be the treatment of choice. All recurrences were in patients over age 40, so although the lesion is histopathologically identical in the younger patients, its biologic behavior seems to be more benign. Since it is possible, however, that invasive disease will ultimately develop in some of the younger patients, careful follow-up is still required.

Adult↗

Silver deposition in the cervix after application of silver nitrate as a cauterising agent.

Large amounts of metallic silver pigment were found in 10 cervical biopsy specimens taken for the histological grading of cervical intraepithelial neoplasia (CIN). The assessment of CIN was made much harder because the pigment obscured the morphological detail of the epithelial cells, and in some it was very difficult to determine whether koilocytosis or CIN I was present. The silver can easily be removed by a simple chemical method.

Adult↗

Verrucous carcinoma of the female genital tract: a review.

The 102 cases of verrucous carcinoma of the female genital tract reported in the world literature have been reviewed. The difficulties in diagnosis of this tumor are discussed; correct diagnosis is heavily dependent on close collaboration between clinician and pathologist, and the provision to the latter of a sufficiently large biopsy specimen. Effective management requires surgical resection, which may at times need to be radical. Radiotherapy and chemotherapy are of doubtful value.

Carcinoma, Papillary↗

Kinetic analysis and probability mapping applied to the detection of ovarian cancer by radioimmunoscintigraphy.

Kinetic analysis with probability mapping is an objective method of serial image analysis applicable to radioimmunoscintigraphy. The technique is described and subjected to clinical testing by comparing the prediction of biopsy histology from the probability map in patients coming to operation. In those with ovarian cancer undergoing second-look laparotomy after completing full courses of chemotherapy, the prediction of histology in 108 biopsy sites was 45 true positives and 38 true negatives, sensitivity 80%, specificity 73%, accuracy 77% p less than 0.001. In patients with tumors less than 2 cm diameter, 41 biopsy sites were predicted with a specificity of 78% and an accuracy of 76%, p less than 0.01. The technique is reducing the need for second-look laparotomy in patients with subclinical and subradiological disease. Such disease is suitable for intraperitoneal radioimmunotherapy.

Adult↗

Localization of radioiodine conjugated to the monoclonal antibody HMFG2 in human ovarian carcinoma: assessment of intravenous and intraperitoneal routes of administration.

The localization of i.p. injected, radioiodine conjugated monoclonal antibody HMFG2 was studied in 18 patients with ovarian carcinoma. Patients were injected i.p. at time points up to 168 h before laparotomy, at which time tumor, ascites, normal tissue, and blood samples were removed and the contained radioactivity measured. In the first 10 patients, localization was compared with that of a simultaneously injected irrelevant (nonspecific) antibody (UJ13A) of the same immunoglobulin class and, in the subsequent 8 patients, with HMFG2 administered i.v. After i.p. injection, HMFG2-radioiodine was found in concentrations of 0.0001-0.0030% of the injected amount per gram in solid tumor, 0.0363-0.02560%/g in ascites, 0.0003-0.0017%/g in blood, and 0.001-0.0012%/g in normal tissue. Tumor:normal tissue ratios of 0.9-10.0 and tumor:blood ratios of 0.3-4.0 were seen up to 168 h after injection. Localization of the HMFG2 conjugate was consistently greater than that of the irrelevant antibody. For solid tumor, the i.v. route of administration resulted in consistently higher absolute levels of HMFG2 conjugate uptake but tumor:blood and tumor:normal tissue ratios were similar. On the other hand the i.p. route of administration offered consistent advantages of 4- to 71-fold over the i.v. route when HMFG2 conjugate localization on ascites cells was examined. Ascites:normal tissue and ascites:blood ratios of up to 512 and 448, respectively, were achieved. After i.p. injection, radioiodine was cleared from the body exponentially with a half-life of 50 h. Maximum circulating blood levels of 8.6 +/- 2.0% injected activity were seen at 48 h and these then decreased with a t 1/2 value of 38 h. Over 80% of injected activity was cleared in the urine as nonprotein bound iodine by 168 h.

Antibodies, Monoclonal↗

Patterns of expression of a tumor associated antigen, defined by the monoclonal antibody HMFG2, in human epithelial ovarian carcinoma. Comparison with expression of the HMFG1, AUA1 and F36/22 antigens.

Binding to the antigen defined by the monoclonal antibody HMFG2 was demonstrated in more than 94% of human epithelial ovarian carcinomas by the indirect immunoperoxidase technique. The extent of the expression of this antigen related to tumor differentiation; well-differentiated tumors expressed more antigen than poorly differentiated tumors. Marked variation of tumor grade and antigen expression was demonstrated in individual tumors and this may be a limiting factor in the use of radioisotope linked HMFG2 for tumor therapy. A similar prevalence was found in the expression of the antigens defined by the monoclonal antibodies HMFG1 and F36/22; whereas the AUA1 antigen was demonstrated in 68% of cases. The patterns of expression of the HMFG1, HMFG2, and F36/22 antigens suggest that they may be related antigens.

Antibodies, Monoclonal↗

Intraperitoneal xenografts of human epithelial ovarian cancer in nude mice.

Using continuous human ovarian cancer cell lines, i.p. xenografts were successfully established in nude mice from four of four attempts. When primary tumor material was used, xenografts grew in 8 of 10 attempts. From these eight, three passageable xenograft cell lines have been established. To our knowledge, this is the first report published of such xenografts. I.p. xenografts closely mimic the clinical behavior of human ovarian cancer, and those developed from primary tumor material maintain close morphological similarity to the parent primary tumor. When expression of placental alkaline phosphatase and the tumor associated antigens defined by the monoclonal antibodies HMFG1, HMFG2, AUA1, and F36/22 by these models was determined, those i.p. xenografts derived from primary tumor material exactly matched the original tumor, while none of the xenografts derived from the cell lines expressed these antigens. These models will be useful for investigating the biology and treatment of ovarian cancer.

Animals↗

The use of myocutaneous flaps following radical excision of the external genitalia.

Myocutaneous and fascio-cutaneous flaps have enabled single stage combined surgical resections and reconstructive procedures to be carried out for locally advanced, non-metastatic carcinoma of the external genitalia. The need for delayed repair procedures with their associated morbidity and prolonged hospital stay is minimised. Functional loss resulting from the removal of the supporting muscle is rarely a problem.

Adenocarcinoma↗

Tumour-associated monoclonal antibodies for the diagnosis and assessment of ovarian cancer.

A tumour-associated radiolabelled monoclonal antibody (HMFG 2) was used to investigate 51 patients who were referred with a pelvic mass and suspected ovarian cancer or recurrent disease. The day before operation the 123I-labelled antibody was injected and the patients then underwent radioimmunoscintigraphy immediately and again 4 and 22 h after the injection. An exploratory laparotomy with appropriate surgery was then performed and the tumours were staged. Tumours were positively imaged 3 min-22 h after injection in all the patients with ovarian cancer, with a mean 0.6% of the injected antibody taken up by the tumour. The presence of HMFG antigen on the tumour was confirmed by immunoperoxidase staining of the surgically-removed tissues. Of the 51 patients, 39 proved to have ovarian cancer. The accuracy of diagnosis and detection of primary and metastatic malignant disease was 95% when correlating pre-operative radioimmune scan findings and laparotomy findings. The procedure is minimally invasive, apparently without side-effects and offers information for tumour detection as an adjunct or alternative to existing methods.

Antibodies, Monoclonal↗

Role of needle biopsy in the investigation of gynecologic malignancy.

Three methods were used to investigate and evaluate patients with primary and persistent/recurrent pelvic malignancy in the gynecologic oncology services at two medical centers. The 22-gauge Chiba needle was utilized with fluoroscopic guidance to perform fine needle aspiration (FNA) of pelvic and paraaortic lymph nodes that appeared abnormal on lymphangiography (LAG). The Tru-cut needle was used to obtain tissue samples from beneath the surface epithelium of the cervix, vaginal vault and parametrium. A disposable, hand-held syringe and 20-gauge needle were used to aspirate supraclavicular and inguinal lymph nodes and cul-de-sac nodules. One hundred thirty-eight patients were evaluated, with positive results in 66 (47.8%). Surgical exploration was used to further investigate 16 negative results that did not correlate with LAG and/or clinical presentation. The sensitivity and predictive value of a negative result for the three methods was Chiba needle FNA/LAG, 62.1% and 65.6%; Tru-cut needle biopsy, 94.4% and 93.5%; and hand-held syringe and needle, 87.5% and 66.7%, respectively. All three techniques proved to be safe, uncomplicated and rapid methods of assessing gynecologic tumor spread. Positive results from these techniques can often replace surgical exploration, with a considerable savings in patient morbidity and hospitalization, and permit additional treatment to proceed without delay. Negative results still require surgical validation.

Biopsy, Needle↗

A phase II study of tamoxifen in ovarian cancer.

A phase II study of tamoxifen was conducted in 22 patients with stage III and IV ovarian cancer who had failed chemotherapy and who had evaluable disease. Tamoxifen was administered at a dose of 20 mg twice daily continuously until evidence of progression. Twenty-one patients had progression of disease within 3 months and one patient had stable disease for 6 months. There were no objective responses to this treatment.

Adult↗

A prospective study of 123I-labeled monoclonal antibody imaging in ovarian cancer.

Thirty patients presenting with a pelvic mass were entered into a prospective study on the use of radioimmunoscintigraphy with the 123I-labeled monoclonal antibody HMFG2. The imaging data was obtained without knowledge of the clinical data and compared with subsequent surgical findings. A false-positive diagnosis of ovarian cancer was made in five of ten patients subsequently shown not to have ovarian cancer; thus the technique cannot be used as a screening test. A true-positive diagnosis was made in 19 out of 20 patients shown subsequently to have ovarian cancer. In 18 of these patients the distribution of uptake closely fitted the surgical findings. Methods of improving these results are described. In conclusion, radioimmunoscintigraphy is of no use in determining whether a pelvic mass is due to ovarian cancer, but has benefit in the evaluation of chemotherapy and may, in the future, prevent the need for second-look operations in some circumstances.

Antibodies, Monoclonal↗