Search PubMed⌕ Search

Biomedical subjects

G D Wilbanks

Publications and source records attributed to G D Wilbanks.

At least 19 recordsLinked to original sources
PubMed2000

Tubal sterilization and risk of cancer of the endometrium.

OBJECTIVE: Surgical sterilization is a common method of contraception among U.S. women. Most surgical sterilizations are tubal ligations, but few studies have investigated their potential impact on endometrial cancer risk. METHODS: A case-control study included 405 women diagnosed with endometrial cancer at 5 U.S. medical centers between 1987 and 1990 and 297 age-, race-, and location-matched controls who were identified by random-digit-dialing. Questionnaires ascertained information on tubal sterilization, and logistic regression models generated odds ratios (ORs) to estimate relative risk. RESULTS: The OR and 95% confidence interval for tubal sterilization, which was reported by 47 cases and 40 controls, was 0.9 (0.6-1.4) before adjustment and 1. 4 (0.8-2.4) after adjustment for age, parity, and oral contraceptive use. Age at surgery, years since surgery, or calendar years of surgery were not associated with endometrial cancer, and associations did not vary according to parity or stage of disease at diagnosis. CONCLUSIONS: Tubal sterilization is not substantially associated with endometrial cancer.

Adult↗
PubMed1999

IL-2 enhances standard IFNgamma/LPS activation of macrophage cytotoxicity to human ovarian carcinoma in vitro: a potential for adoptive cellular immunotherapy.

OBJECTIVE: The objective was to evaluate the enhancement of human peritoneal macrophage cytotoxic in vitro activity by the addition of interleukin-2 (IL-2) to the standard interferon gama (IFNgamma) and lipopolysaccharide (LPS) activation procedure used for cellular adoptive immunotherapy in a human ovarian cancer system. This cytotoxic effect of these activated macrophages was tested on cells from ovarian cancers of various stages, histology type, and grade, both prior to chemotherapy and at recurrence, in ovarian carcinoma cells lines and normal cells. Increased activation of the macrophage may make it a better candidate for intraperitoneal cellular adoptive immunotherapy as a component of ovarian cancer therapy. This was not a study of the mechanism of macrophage killing. METHODS: Ascites specimens were collected from 24 ovarian cancer patients at the time of surgery or by paracentesis. The mononuclear cell fraction was isolated by discontinuous density gradient centrifugation and used as a cellular source of peritoneal macrophages (PMs) and primary cultured ovarian cancer cells. PMs were separated by 1-h adhesion followed by intensive washing to remove floating cells. The floating cells were cultured for 24 h which left the cancer cells attached after unattached cells were removed by washing. These cells formed a monolayer of cancer cells, which could be subcultured in 22 patients. The cells from the third to fifth passages were used as target cells without coculture with other cells. PMs were identified by latex ingestion, and their purity after isolation by adhesion culture was tested by flow cytometry and immunofluorescence. PMs were activated by culturing in the presence of IFNgamma, with or without IL-2, for 18 h followed by the addition of LPS 6 h prior to use as effector cells in cytotoxicity assays. Ovarian cancer cells of both established cell lines and primary cultures were labeled with (51)Cr and utilized as target cells to quantitatively measure PM-mediated cytotoxicity. Ovarian cancer cells were also cocultured with PMs for morphologic observations to provide supporting evidence to the cytotoxicity assays. RESULTS: IL-2 enhances the cytotoxicity of the standard IFNgamma/LPS macrophage activation in this system. Peritoneal macrophages so activated are cytotoxic to autologous and allogenic primary cultured ovarian tumors and to ovarian carcinoma cell lines. The macrophages are cytotoxic to cells both prior to treatment and at recurrence, but the data from the few recurrent patients did reach statistical significance. This cytotoxicity is not MHC associated. Normal cells are minimally affected. CONCLUSIONS: IL-2 augmented the standard IFNgamma/LPS method of activating peritoneal macrophage cell killing of human ovarian cancer cells in this in vitro system. The cell killing occurred with autologous and allogenic tumor cells from patients with primary and possibly recurrent tumors. Activated PMs minimally affected the normal cells tested. This enhanced activation may improve the disappointing results of previous adoptive cellular immunotherapy human trials and should be considered for ovarian cancer clinical trials.

Adult↗
PubMed1998

Evidence for a common etiology for endometrial carcinomas and malignant mixed mullerian tumors.

OBJECTIVE: To elucidate factors linked to the development of malignant mixed mullerian tumors (MMMT) and determine whether the risk factor profile for these tumors corresponds with that for the more common endometrial carcinomas. METHODS: A multicenter case-control study of 424 women diagnosed with endometrial carcinoma, 29 women diagnosed with MMMT, and 320 community controls was conducted. Review of pathological reports and slides was performed to classify cases by histological type. All participants were asked to respond to a questionnaire which ascertained information on exposure to factors postulated to be linked to the development of uterine tumors. RESULTS: Women with endometrial carcinomas and MMMTs were similar with respect to age and educational attainment. Women diagnosed with MMMTs were more likely than those diagnosed with carcinomas to be of African-American descent (28% vs 4%; P = 0.001). Weight, exogenous estrogen use, and nulliparity were related to risk of both tumor types. Marked obesity was associated with a 4.8-fold (95% CI = 3.0,7.6) increase in risk of carcinoma and a 3.2-fold (95% CI = 1.1,9.1) increase in risk of MMMT development. Use of exogenous estrogens increased the odds of developing carcinomas by 2-fold (95% CI = 1.3,3.2) and that of developing MMMTs by 1.8-fold (95% CI = 0.57,5.5). Nulliparity was associated with a 2.9-fold (95% CI = 1.9,4.8) increase in risk of carcinomas and a 1.7-fold (95% CI = 0.53,5.6) increase in risk of MMMTs. Oral contraceptive use protected against the development of both carcinomas (OR = 0.39; 95% CI = 0.26,0.58) and MMMTs (OR = 0.76; 95% CI = 0.25,2.3). Current smokers were at a reduced risk of developing endometrial carcinomas (OR = 0.34; 95% CI = 0.21,0.55) and MMMTs (OR = 0.57; 95% CI = 0.15,2.3), while former smokers were at an increased risk of MMMT (OR = 2.7; 95% CI = 1.1,6.8) but not carcinoma development (OR = 0.81; 95% CI = 0.56,1.2). CONCLUSION: Results from this study suggest that MMMTs and carcinomas have a similar risk factor profile. This observation is compatible with the hypothesis that the pathogenesis of these two histological types of uterine tumors is similar.

Adult↗
PubMed1998

Analysis of histopathological features of endometrioid uterine carcinomas and epidemiologic risk factors.

A large case-control study was performed to determine whether risk factors for endometrioid carcinoma, the most common type of endometrial cancer, vary according to the histological features of the tumor. Study subjects consisted of 328 women with newly diagnosed endometrioid adenocarcinoma and 320 population-based control subjects. Variables studied included age at menarche, menopausal estrogen use, weight, parity, cigarette smoking, and oral contraceptive use. The risk factor profile for endometrioid carcinomas with and without squamous differentiation was very similar. No striking differences in risk factors were observed between endometrioid cancers with and without adjacent endometrial hyperplasia. Finally, none of the risk factors varied substantially between early-stage and late-stage tumors or low-grade and high-grade tumors. In summary, this study indicates that risk factors for endometrioid carcinomas are not related to the morphological features of the tumor.

Adult↗
PubMed1997

The efficacy and safety of Skinner herpes simplex vaccine towards modulation of herpes genitalis; report of a prospective double-blind placebo-controlled trial.

A randomised, placebo-controlled, multi-centre trial of intracellular subunit herpes simplex virus (HSV) type 1 vaccine NFU.Ac.HSV-1(S-)MRC (Skinner vaccine) was conducted at three medical centres in the United States. Subjects with documented herpes genitalis of at least 1-year duration and a history of six or more genital HSV recurrences in the 12 months prior to study entry were randomised to receive vaccine or placebo at 0, 1 and 2 months. Vaccination induced significant neutralising, enzyme-linked immunosorbent assay and lymphocyte transformation response to HSV-1 antigen. The frequency of recurrences was reduced in the vaccinated female patients at both 3 and 6 months following vaccination with an overall reduction in patients of both sexes which did not reach statistical significance. Recurrence severity was reduced as measured by decreased number of lesions and associated symptoms per recurrence (P = 0.04). The data suggest that clinical manifestations of latent HSV genital infection may be modified by therapeutic immunisation.

Adult↗
PubMed1997

Intrauterine device use and endometrial cancer risk.

BACKGROUND: Because intrauterine devices (IUD) invoke acute and chronic inflammatory responses in the endometrium, it is possible that prolonged insertion of an IUD could induce endometrial cancer. METHODS: We examined the relation between use of an IUD and endometrial cancer risk using data from a multicentre case-control study involving 405 endometrial cancer cases and 297 population controls. RESULTS: A total of 20 (4.9%) cases and 34 (11.4%) controls reported any use of an IUD. After adjustment for potential confounders, IUD use was not associated with an increased risk of endometrial cancer (RR = 0.56 for ever use; 95% CI: 0.3-1.0). Little reduction in risk was observed among women who last used an IUD within 10 years of the index date (RR = 0.84; 95% CI: 0.3-2.4) but risk was decreased among women who used an IUD in the more distant past (RR = 0.45; 95% CI: 0.2-1.0). Risk did not vary consistently with number of years of IUD use or with years since first use. Risk was not increased among women who used inert devices (RR = 0.46; 95% CI: 0.3-3.6) or those who used devices containing copper (RR = 1.08; 95% CI: 0.1-3.6). CONCLUSION: These data are reassuring in that they do not provide any evidence of an increased risk of endometrial cancer among women who have used IUD.

Adult↗
PubMed1997

Risk factors and hormone levels in patients with serous and endometrioid uterine carcinomas.

We performed a multi-institutional, incident case-control study of 328 endometrioid and 26 serous carcinomas to assess whether risk factors and circulating hormone levels in women with serous carcinoma differ from the expected profile for endometrial carcinoma We also evaluated exposures potentially related to endometrial cancer risk, anthropometric measurements, and circulating levels of sex hormones and related carrier proteins. Histopathologic specimens were reviewed without knowledge of the other data. As expected, a statistically significant association was observed for high body mass index (BMI) (relative risk, 3.5) and use of menopausal estrogens (relative risk, 2.4) in the endometrioid carcinoma cases, whereas serous carcinomas were not strongly associated with these factors. Smoking and oral contraceptive use decreased risk for both tumor types. For five of six sex hormones tested, age-adjusted mean serum levels in patients with serous carcinoma were significantly lower than those in women with endometrioid carcinoma. After adjustment for BMI, these differences were narrowed, but levels of albumin-bound estradiol and estrone remained significantly lower in the serous cases. Age and BMI-adjusted levels of sex hormone-binding globulin were significantly higher in patients with serous carcinoma than in women with endometrioid carcinomas. In conclusion, risk factors and sex hormone levels in patients with uterine serous carcinoma seem to differ from those in women with endometrioid carcinoma, suggesting that there may be at least two different pathways of endometrial carcinogenesis.

Age Factors↗
PubMed1996

Case-control study of endogenous steroid hormones and endometrial cancer.

BACKGROUND: It has been suggested that identified risk factors for endometrial cancer operate through a single etiologic pathway, i.e., exposure to relatively high levels of unopposed estrogen (estrogen in the absence of progestins). Only a few studies, however, have addressed this issue directly. PURPOSE: We assessed the risk of developing endometrial cancer among both premenopausal and postmenopausal women in relation to the circulating levels of steroid hormones and sex hormone-binding globulin (SHBG). The independent effect of hormones was assessed after adjustment for other known risk factors. METHODS: The data used in the analysis are from a case-control study conducted in five geographic regions in the United States. Incident cases were newly diagnosed during the period from June 1, 1987, through May 15, 1990. The case patients, aged 20-74 years, were matched to control subjects by age, race, and geographic region. The community control subjects were obtained by random-digit-dialing procedures (for subjects 20-64 years old) and from files of the Health Care Financing Administration (for subjects > or = 65 years old). Additional control subjects who were having a hysterectomy performed for benign conditions were obtained from the participating centers. Women reporting use of exogenous estrogens or oral contraceptives within 6 months of interview were excluded, resulting in 68 case patients and 107 control subjects among premenopausal women and 208 case patients and 209 control subjects among postmenopausal women. The hormone analyses were performed on blood samples obtained from case patients or from hysterectomy control subjects before surgery. The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by use of an unconditional logistic regression analysis after we controlled for matching variables and potential confounders. All P values were two-sided. RESULTS: High circulating levels of androstenedione were associated with 3.6-fold and 2.8-fold increased risks among premenopausal and postmenopausal women, respectively, after adjustment for other factors (P for trend = .01 and < .001, respectively). Risks related to other hormone fractions varied by menopausal status. Among postmenopausal women, a reduced risk was associated with high SHBG levels and persisted after adjustment was made for obesity and other factors (OR = 0.51; 95% CI = 0.27-0.95). High estrone levels were associated with increased risk (OR = 3.8; 95% CI = 2.2-6.6), although adjustment for other risk factors (particularly body mass index) diminished the effect (OR = 2.2; 95% CI = 1.2-4.4). Albumin-bound estradiol (E2), a marker of the bioavailable fraction, also remained an important risk factor after adjustment was made for other factors (OR = 2.0; 95% CI = 1.0-3.9). In contrast, high concentrations of total, free, and albumin-bound E2 were unrelated to increased risk in premenopausal women. In both premenopausal and postmenopausal groups, risks associated with obesity and fat distribution were not affected by adjustment for hormones. CONCLUSION: High endogenous levels of unopposed estrogen are related to increased risk of endometrial cancer, but their independence from other risk factors is inconsistent with being a common underlying biologic pathway through which all risk factors for endometrial cancer operate. IMPLICATIONS: Further research should focus on alternative endocrinologic mechanisms for risk associated with obesity and body fat distribution and for the biologic relevance of the increased risk associated with androstenedione in both premenopausal and postmenopausal disease.

Adult↗
PubMed1996

Interferon-alpha and all-trans-retinoic acid reversibly inhibit the in vitro proliferation of cell lines derived from cervical cancers.

Interferon and retinoic acid are active agents for the treatment of cervical cancer, but their mechanisms of action are unclear. Results of [3H]thymidine uptake assays showed that exposure to pharmacologic concentrations of interferon-alpha (IFN-alpha) and all-trans-retinoic acid (RA) for 72 hr inhibited growth of the cervical cancer cell lines ME-180, 283, SiHa, C33-A, 621, CaSki, HeLa, and B132, CaSki and SiHa cells continuously exposed to IFN-alpha or RA or both for 9 days developed resistance to growth inhibition, and growth resumed at a rate comparable to control after removal of agents. Similar assays showed no significant difference in effects of RA and its cis isomer. Assays for lactate dehydrogenase release revealed no significant lysis of any cell line following exposure to IFN-alpha, RA, or their combination. In organotypic culture, cells grew in a pattern histologically similar to carcinoma in situ, and exposure to IFN-alpha and RA for 14 days yielded no change in this pattern. Immunohistochemical analysis showed no change in cytokeratin expression by cells in organotypic or monolayer culture. The major in vitro effect of IFN-alpha and RA on cervical cancer cell lines appears to be reversible inhibition of proliferation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

All-trans-retinoic acid inhibits the proliferation of cell lines derived from human cervical neoplasia.

The purpose of this study was to determine whether all-trans-retinoic acid (RA) can inhibit the growth of cervical neoplastic cells by inducing differentiation or by increasing the secretion of transforming growth factor-beta (TGF-beta). Normal and HPV DNA-positive cervical cells (2 cell lines derived from cervical intraepithelial neoplasia (CIN), 2 HPV DNA-transfected cell lines, and 6 cervical carcinoma cell lines) were treated with RA (1 to 1000 nM), and both total viable cell count and [3H]thymidine incorporation were used to evaluate proliferation. In vitro differentiation was evaluated in organotypic (collagen gel raft) cultures with hematoxylin/eosin staining, and using specific immunostaining for fillagrin and cytokeratin 10. TGF-beta 1 and TGF-beta 2 secretion were measured with specific SELISAs. One-way analysis of variance and t tests were performed. RA causes a dose-dependent (P<0.05) growth arrest of comparable magnitude in normal ectocervical cells, in HPV DNA-transfected cell lines, in CIN-derived cell lines, and in four of six carcinoma cell lines. Endocervical cells and two carcinoma cell lines are unaffected. In vitro differentiation is decreased in CIN cells and is unchanged in carcinomas treated with RA as compared to control. Secretion of either TGF-beta 1 or TGF-beta 2 is significantly increased (P<0.05) in response to RA, both in RA-sensitive and in RA-resistant cells. RA induces growth inhibition in cervical neoplastic cell lines, including cervical carcinoma cells. This does not appear to be the result of increased differentiation or of increased TGF-beta secretion.

Cell Count↗
PubMed1996

A bleomycin/ifosfamide/cisplatin regimen exhibits poor activity against persistent or recurrent squamous gynecologic cancers.

Persistent or recurrent squamous malignancies of the female genital tract are usually incurable by conventional therapy, and results of single agent chemotherapy have been disappointing. We undertook this study to confirm a previously reported response rate of 69%, using a regimen of bleomycin 30U, ifosfamide 5g/m2 with mesna 6g/m2, and cisplatin 50 mg/m2 (BIP) for recurrent cervical cancer. This regimen was used to treat persistent or recurrent squamous cancers in women with cervical cancer (n = 11), vaginal cancer (n = 1) and vulvar cancer (n = 1). Results were reviewed retrospectively and toxicities graded according to the criteria of the Gynecologic Oncology Group. No complete responses were seen. One patient had a partial response (10%, 95% confidence interval 0-28%). Five patients (50%), exhibiting stable disease during therapy with BIP, progressed after cessation of therapy. Of 9 women with symptoms after one cycle. Significant toxicities included neutropenic fever (3 grade 3, 3 grade 4), emesis (1 grade 3), confusion (2 grade 4), vaginal bleeding (2 grade 3), and renal failure (1 grade 3). Eight patients were transfused with a total of 28 units of red cells. After 23 months of follow-up, all patients were dead of disease. Mean survival was 10 months. Toxicity associated with this regimen can be significant, and results appear no better than those reported with single agent therapy.

Adult↗
PubMed1995

Smoking, obesity, and survival in squamous cell carcinoma of the vulva.

One hundred thirty-six patients with invasive squamous cell carcinoma of the vulva were studied retrospectively to determine prognostic factors for survival. In the regression analysis, three variables were statistically significantly related to survival: smoking history, tumor size, and node status. Smokers had a 6.3 times greater risk than nonsmokers, node positivity imparted an 8.3 times greater risk than node negativity, and for each 1-cm increase in the size of the tumor, the risk of death increased by 46%. A relative decrease in survival in smokers was observed, despite a younger age and fewer positive nodes at diagnosis compared to nonsmokers. Increased surveillance in these patients may be warranted.

Adult↗
PubMed1995

Recurrence patterns and complications in endometrial adenocarcinoma with cervical involvement.

BACKGROUND: Cervical involvement in endometrial carcinoma is a diverse entity, and the optimal management of these patients is not well understood. METHODS: Recurrence patterns and complications in 202 patients with histologically confirmed endometrial carcinoma with cervical involvement were retrospectively studied. RESULTS: The 5-year actuarial survival rate for all patients was 65%. Recurrences were documented in 80 (40%) of the patients, and the overall long-term survival rate in this group was 4%. Patients treated with radical hysterectomy (n = 33) had a 6% isolated pelvic recurrence rate and the lowest serious complication rate among the five treatment groups despite having the highest frequency of risk factors for recurrence among any of the groups studied. Patients treated with extrafascial hysterectomy alone (n = 37) had a 14% pelvic recurrence rate and very few complications. When radiotherapy preceded extrafascial hysterectomy (n = 37), the frequency of pelvic recurrences was 30%, and 19% experienced serious gastrointestinal or genitourinary tract complications. When radiotherapy followed extrafascial hysterectomy (n = 68), the pelvic recurrence rate was 24%, and 13% experienced serious complications. Overall, 24% of patients (49 of 202) had isolated pelvic recurrences, whereas 10% (21 of 202) had isolated distant recurrences and 5% (10 of 202) were simultaneously diagnosed with both pelvic and distant recurrences. CONCLUSIONS: This large data base suggests that older conventional forms of therapy, particularly those using preoperative radiotherapy, subject the patient to significant morbidity over a 5- to 10-year period and, in terms of local control, are not necessarily superior to therapeutic modalities using primary surgical evaluation, such as radical hysterectomy. Consideration of primary surgery should be given in the appropriate situation, and radical hysterectomy should be considered when gross cervical involvement is encountered and intraoperative exploration does not show obvious extrauterine disease.

Actuarial Analysis↗
PubMed1994

Prognostic indicators of survival in advanced endometrial cancer.

Advanced endometrial cancer represents 14% of all stages but 54% of all deaths attributed to endometrial cancer. From 1973 to 1990, the charts of 137 patients with endometrial cancer (Stage III and IV) treated by the section of Gynecologic Oncology at Rush Medical College were retrospectively reviewed. The log rank method was used for univariate analysis and Cox proportional hazards regression was used for multivariate analysis. The patients were stratified as follows: Stage III, 92 (67.2%), Stage IV, 45 (32.8%); Grade 1, 15 (10.9%), Grade 2, 47 (34.3%), Grade 3, 67 (48.9%); adenocarcinoma, 93 (67.9%), adenosquamous, 18 (13.1%), adenoacanthoma, 2 (1.5%), clear cell, 1 (0.7%), papillary serous, 23 (16.8%). Using univariate analysis, median survival was 1.71 years for Stage III versus 0.68 years for Stage IV. Median survival based on treatment was as follows: radiotherapy (RT) only (n = 16), 0.89 years, surgery only (n = 36), 0.75 years, preoperative RT+surgery (n = 7), 2.5 years, surgery+postoperative RT (n = 56), 2.63 years, and other treatments (hormonal only n = 12, chemotherapy only n = 1, and no treatment n = 9), 0.6 years. Patients with vaginal extension survived a median of 0.82 years, versus 2.49 years without this factor (P = 0.002). Patients with clinically apparent parametrial involvement survived a median of 0.70 years versus 2.65 years without this factor (P = 0.0003). Multivariate analysis was possible via a surgical database (n = 99). Age > 60 (P = 0.01), parametrial involvement (P = 0.04), and abdominal metastases (P = 0.003) were significant prognostic indicators. Papillary or clear cell histology, advanced grade, and mode of treatment were not significant. Patients with abdominal metastases or parametrial extension of tumor have a significant decrease in mean survival.

Age Factors↗