PubMed Health⌕ Search

Biomedical subjects

William T Creasman

Publications and source records attributed to William T Creasman.

12 recordsLinked to original sources

Should symptomatic menopausal women be offered hormone therapy?

UNLABELLED: Many physicians remain uncertain about prescribing hormone therapy for symptomatic women at the onset of menopause. The American Society for Reproductive Medicine (ASRM) convened a multidisciplinary group of healthcare providers to discuss the efficacy and risks of hormone therapy for symptomatic women, and to determine whether it would be appropriate to treat women at the onset of menopause who were complaining of menopausal symptoms. MAJOR FINDINGS: Numerous controlled clinical trials consistently demonstrate that hormone therapy, administered via oral, transdermal, or vaginal routes, is the most effective treatment for vasomotor symptoms. Topical vaginal formulations of hormone therapy should be preferred when prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy. Data from the Women's Health Initiative indicate that the overall attributable risk of invasive breast cancer in women receiving estrogen plus progestin was 8 more cases per 10,000 women-years. No increased risk for invasive breast cancer was detected for women who never used hormone therapy in the past or for those receiving estrogen only. Hormone therapy is not effective for the treatment of cardiovascular disease and that the risk of cardiovascular disease with hormone therapy is principally in older women who are considerably postmenopause. CONCLUSIONS: Healthy symptomatic women should be offered the option of hormone therapy for menopausal symptoms. Symptom relief with hormone therapy for many younger women (at the onset of menopause) with menopausal symptoms outweighs the risks and may provide an overall improvement in quality of life. Hormone therapy should be individualized for symptomatic women. This involves tailoring the regimen and dose to individual needs.

Aged↗

Serum vascular endothelial growth factor C (VEGF-C) as a specific biomarker for advanced cervical cancer: Relationship to insulin-like growth factor II (IGF-II), IGF binding protein 3 (IGF-BP3) and VEGF-A [corrected].

OBJECTIVES: An early non-invasive diagnosis of cervical cancer and its metastasis can save lives. We have shown that serum IGF-II levels can be effectively used for a specific early diagnosis of cervical cancer. Here, we shall determine if serum levels of vascular endothelial growth factors B and C (VEGF-A [corrected] VEGF-C) associated with vasculogenic and lymphogenic metastasis may be used for an early diagnosis of advanced metastatic cervical cancer and compare these levels with those of the serum IGF-II and IGF-binding protein 3 (IGF-BP3). MATERIAL AND METHODS: (a) Serum levels of IGF-II, IGF-BP3, VEGF-A [corrected] (VEGF(165)) and VEGF-C (ELISA kits) were determined in: 82 controls with normal Pap smears; 29 women with atypical squamous cells of undetermined significance (ASCUS) and normal cervical biopsy; 46 ASCUS and cervical intraepithelial neoplasia (CIN) on biopsy; 8 pre-therapy CIN-I; 23 successfully treated CIN-I; 75 persistent CIN-I; 14 CIN-II/III pre-therapy; 14 successfully treated CIN-II/III; 70 persistent CIN-II/III; 86 pre-therapy cervical cancer; 26 in early grades of cervical cancer; 21 in late grades of cervical cancer; 22 cervical cancer patients in remission; 50 persistent cervical cancer; 18 with ovarian cancer; and 57 with endometrial cancer. (b) Serial serum samples collected over 5 years in 5 women with progressing cervical cancer were also tested. (c) Serum and tissue VEGF-C were enumerated in 20 matched serum (ELISA) and tissue (semi-quantitative immunofluorescent antibody assay) samples from controls, early cervical cancer, late cervical cancer, ovarian cancer and endometrial cancer patients. Student's t test, chi-square analysis and linear regression analysis were used. RESULTS: (a) As anticipated, serum IGF-II levels were elevated as early as ASCUS with CIN on biopsy and continued to be elevated in CIN (all grades; pre-therapy and persistent) and cervical cancer (pre-therapy, early, late and persistent). Serum IGF-II levels were normal in ASCUS with normal biopsy, successfully treated CIN-I, II/III, cervical cancer as well as pre-therapy ovarian and endometrial cancers (therapy efficacy: P < 0.0001 by chi-square analysis). Serum IGF-BP3 showed a significant decrease with advancing disease. Serum VEGF-A [corrected] levels were the highest in pre-therapy, early, advanced and persistent cervical cancer, as well as in ovarian and endometrial cancers. Serum VEGF-C levels, on the other hand, were the highest in late and persistent cervical cancers, but not in ovarian or endometrial cancers. (b) In the 5 women with serial samples, the serum levels of the growth factors showed similar trends. (c) VEGF-C levels in serum and tissue were elevated in cervical cancers especially in advanced grades, while they were normal in serum and tissue from the controls and women with ovarian and endometrial cancers. There was a highly significant positive correlation between VEGF-C and IGF-II and a negative correlation between IGF-BP3 and VEGF-C (P < 0.0001). CONCLUSION: Serum IGF-II up-regulation is specific to cervical cancer and helps in the early diagnosis of malignant proliferation, while serum VEGF-C up-regulation appears to be a unique marker for an early diagnosis of cervical cancer metastasis. VEGF-C and IGF-II systems appear to be interrelated in cervical cancer, contributing to the early malignant cell proliferation and lympho-vascular metastasis. Serum IGF-BP3 and VEGF-A [corrected] appear to be common markers for all gynecological cancers.

Biomarkers, Tumor↗

Breast cancer: the role of hormone therapy.

The possible association of estrogen (E) with or without progestin (P) and breast cancer has been addressed in many studies for several decades. The recent reported prospective double-blind Women's Health Initiative (WHI) study suggests that E + P increases the risk of breast cancer if a woman is an average of 63 years old when she begins replacement therapy. One third of the patients in this study were 70 to 79 years of age when E + P was begun--obviously several decades past menopausal. Retrospective and observational studies suggest protection or no increased risk. The WHI-E only study actually notes a 23% reduction in breast cancer compared with the placebo. It would appear from a review of the literature that if there is an increased risk for breast cancer with E or E + P, it is minimal.

Aged↗

Vaginal cancers.

PURPOSE OF REVIEW: Vaginal neoplasia is one of the rarest of malignancies. Intraepithelial lesions are usually first identified by an abnormal Pap smear in a woman without a cervix. Surgery or ablation of the epithelium is usually highly successful. RECENT FINDINGS: There have not been any findings of significance since 2003 to include in this review. SUMMARY: Invasive cancer is usually located in the upper one-third of the vagina. If staged early, radical surgery can be curative as well as radiation therapy. Like cervical cancer, a more advanced stage is treated with radiation therapy, but with poorer survival rates than cervical cancer.

Carcinoma in Situ↗

Hormone replacement therapy after cancers.

PURPOSE OF REVIEW: The role of female hormones in estrogen-dependent cancers has been debated for years. This is particularly true of breast cancer. Retrospective, case, and cohort control studies usually have suggested no influence. The Women's Health Initiative study in 2002, a prospective double-blind study, noted an increased risk of breast cancer if estrogen plus progesterone was given. In the estrogen-only arm of that study, a decreased (not significant) risk of breast cancer was noted. With this controversy, can estrogen be given safely to a woman who has been treated for breast cancer? The relation between endometrial cancer and unopposed estrogen is well established. With clear-cut evidence of this relation, is there evidence to suggest a role for replacement therapy in women who have been treated for endometrial cancer? RECENT FINDINGS: Several case-control and cohort studies have noted either no increased risk or actually less risk of recurrence in women taking estrogen after therapy after breast cancer. Although the general consensus is that such a recommendation is contraindicated, the data do not support this admonition. The current data suggest that replacement therapy can be given to the woman who has been treated for endometrial cancer. SUMMARY: There seems to be little if any risk in giving hormone replacement therapy to women who have had breast or endometrial cancer. There are no data to suggest that hormone replacement therapy is contraindicated in women who have been treated for cervical or ovarian cancer.

Antineoplastic Agents, Hormonal↗

Is lymph vascular space involvement an independent prognostic factor in early cervical cancer?

OBJECTIVE: To determine whether lymph vascular space involvement (LVSI) in women with early cervical carcinoma is an independent prognostic factor. METHODS: The literature was reviewed using Medline and known literature to determine if LVSI is an independent risk factor as determined by multivariant analysis with survival being the end point in patients undergoing radical hysterectomy and pelvic lymphadenopathy. RESULTS: A total of 25 articles were identified that satisfied the evaluation criteria. Only three (12%) identified LVSI as an independent risk factor while 88% and 61% of those evaluated, noted lymph node metastasis and tumor size/depth of invasion to be significant risk factors for survival. CONCLUSIONS: Using LVSI as the sole determining factor for consideration of post radical hysterectomy radiotherapy appears questionable.

Female↗

Prognosis of papillary serous, clear cell, and grade 3 stage I carcinoma of the endometrium.

OBJECTIVE: The purpose of this study was to evaluate patients with uterine papillary serous carcinoma (UPSC), clear cell (CC), and grade 3 endometrioid (G3) surgically stage I endometrial cancer. METHODS: The 25th Annual Report (AR) of FIGO was used to identify patients with endometrial cancers who were surgically staged. For comparison, all cancers reported were evaluated with particular interest in patients with stage I UPSC, CC, and G3. Incidence, substage, post-surgical treatment, and survival were identified. RESULTS: Of 5694 endometrial cancer patients reported to the AR, 3996 (70%) were surgically stage I. There were 148 UPSC, 59 CC, and 325 with G3 lesions. UPSC and CC represent 5.2% of all stage I cancers while 8.1% are G3. Although there were greater number of UPSC, CC, and G3 with extrauterine disease, about 50% of UPSC and CC were stage I. This compares to 81% for G1, 68% for G2, and only 42% for G3. There were more IA cancers with UPSC and CC than G3 (22%, 33%, and 17%, respectively). Survival (5 years) for UPSC and CC was 72% and 81%, respectively, compared to 76% for G3 lesions. Postoperative radiation improved survival somewhat (6-8%) but the difference was not significant. CONCLUSION: UPSC and CC histotypes when diagnosed as stage I have a better survival than commonly perceived and equal to G3 endometrioid cancers. Postoperative radiation improves survival but not significantly so. The role of chemotherapy has not been defined.

Adenocarcinoma↗

Circulating levels of insulin-like growth factor-II and IGF-binding protein 3 in cervical cancer.

OBJECTIVE: We aimed to further document that elevated levels of circulating insulin-like growth factor II (IGF-II) are associated with cervical cancer and to test the hypothesis that there may be an inverse association between IGF-II and IGF-binding protein 3 (IGF-BP3). METHODS: Serum IGF-II and IGF-BP3 levels were measured, using ELISA kits (Diagnostic Systems Laboratories), in 23 controls; 16 ASC-US with normal biopsies; 14 ASC-US with advanced CIN; 2 pretherapy CIN-I; 8 successfully treated CIN-I; 24 persistent CIN I; 14 pretherapy CIN II/III; 10 posttherapy CIN II/III with normal biopsies; 18 persistent CIN-II/III; 7 with pretherapy cervical cancer; 19 with posttherapy cervical cancer under remission; 15 with posttherapy persistent/recurrent cervical cancer; 10 with persistent ovarian or endometrial cancer; and 3 with endometrial or vulvar with cervical cancer. Student's t test and linear regression analysis were used. RESULTS: Compared to controls (493 +/- 90 ng/ml) and women with other gynecological cancers, serum IGF-II levels were significantly increased in women with ASC-US, with advanced CIN on biopsy (P < 0.0001), persistent CIN-I (993 +/- 262 ng/ml; P < 0.0001), pretherapy advanced CIN (1086 +/- 240; P < 0.0001), pretherapy cervical cancer patients (1746 +/- 318 ng/ml; P < 0.0001) and posttherapy persistent/recurrent CIN (1094 +/- 300; P < 0.0001); and cervical cancer (1395 +/- 189; P < 0.0001). After therapy, the IGF-II levels returned to normal in both CIN and cervical cancer patients under remission. Elevated serum IGF-II levels had 100% sensitivity and 87% specificity for cervical cancer and 81% sensitivity and 82% specificity for CIN. The levels of IGF-BP3 were significantly reduced in women with CIN before and after therapy (P < 0.0001) and in cervical cancer patients before and after therapy (P < 0.001). There was an inverse relationship between serum IGF-II and BP-3 levels (P < 0.01). Decreased serum IGF-BP3 levels had a sensitivity of 72% and specificity of 75% for cervical cancer and 81% sensitivity and 83% specificity for CIN. When both markers were considered together the sensitivity was 72% and specificity 84% for cervical cancer, while for CIN, the sensitivity was 57% and specificity 81%. CONCLUSION: Serum IGF-II may be a reliable marker for early diagnosis and monitoring therapy efficacy (sensitivity and specificity of 100% versus normal controls), while IGF-BP3 levels can be reliably used to predict prognosis.

Biomarkers, Tumor↗

Expression of cyclooxygenase-2 in cervical, endometrial, and ovarian malignancies.

OBJECTIVE: This study was undertaken to compare the presence of cyclooxygenase-2 (COX-2) levels between normal and malignant cervix, endometrium, and ovary. STUDY DESIGN: Semiquantitative immunofluorescent assays for COX-2 were performed on sections of cervical squamous cell carcinoma (n = 12), endometrial adenocarcinoma (n = 13), and ovarian serous adenocarcinoma (n = 9). Levels of immunofluorescence for each sample were objectively measured, categorized as high, moderate, or negative expression and compared with normal cervical (n = 14), endometrial (n = 15), and ovarian (n = 13) tissue with the Fisher exact test. RESULTS: Normal cervical tissue expressed COX-2 more frequently than cervical cancer (50% vs 23%), but the difference was not significant (P =.247). COX-2 was rarely present in normal endometrium (7%) and normal ovarian epithelium (0%) and was usually present in endometrial adenocarcinoma (69%, P <.001) and ovarian serous cystadenocarcinoma (89%, P <.001). CONCLUSION: In this cohort, COX-2 expression is significantly more common in endometrial adenocarcinoma and ovarian serous cystadenocarcinoma, but not in cervical squamous carcinoma, compared with normal tissue.

Adenocarcinoma↗

Phase II trial of pyrazoloacridine in recurrent platinum-sensitive ovarian cancer: a Gynecologic Oncology Group study.

OBJECTIVES: Acridine compounds are believed to exhibit anti-cancer cytotoxic effects because of interactions with both DNA and RNA. Pyrazoloacridine (PZA) (NSC No. 366140) is a 9-methoxyacridine compound that has demonstrated activity in some patients with solid tumors. The Gynecologic Oncology Group (GOG) performed a phase II trial of PZA to determine the response rate of this agent in patients with recurrent platinum-sensitive ovarian cancer. METHODS: Patients with recurrent ovarian cancer who experienced a progression-free interval of greater than 6 months after response to platinum-based chemotherapy are defined as platinum sensitive by the GOG and were eligible for this trial. PZA was administered at a dose of 750 mg/m2 intravenously over 3 h every 3 weeks. RESULTS: Among 42 evaluable patients, there was 1 (2.4%) complete response and 9 (21.5%) partial responses, including 1 patient who had a partial response after 10 courses of treatment. The major toxicity was neutropenia; severe thrombocytopenia was infrequent. CONCLUSION: PZA demonstrates moderate activity in this chemotherapy-sensitive population, with manageable hematologic toxicity. Due to its unique mechanism of action and preclinical activity against hypoxic and noncycling cells, PZA should be considered for evaluation in combination with other active agents.

Acridines↗