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Biomedical subjects

G L Goldberg

Publications and source records attributed to G L Goldberg.

At least 19 recordsLinked to original sources
PubMed2001

Pattern of lymph node metastases in clinically unilateral stage I invasive epithelial ovarian carcinomas.

PURPOSE: There is controversy regarding the pattern of lymphatic spread in unilateral stage I invasive ovarian carcinomas. The purpose of this study is to describe the incidence and distribution of lymph node (LN) metastases in ovarian carcinomas clinically confined to one ovary. METHODS: Ninety-six patients with disease visibly confined to one ovary were identified. Pathology reports were reviewed to identify metastatic LN involvement, number of involved nodes, and their locations. Patients with gross disease in the pelvis or abdomen or those who had grossly positive LNs removed for debulking were excluded from this review. RESULTS: Fourteen of ninety-six patients (15%) had microscopically positive LNs on pathologic review. All of these 14 patients had grade 3 tumors. Grade 3 tumors were more commonly seen in LN-positive versus LN-negative patients (P < 0.001). Pelvic nodes were positive in 7 patients (50%), paraaortic nodes in 5 patients (36%), and both in 2 patients (14%). Forty-two patients had LN sampling only on the side ipsilateral to the neoplastic ovary, 4 of whom (10%) had LN metastases. Fifty-four patients had bilateral sampling performed, 10 of whom (19%) had LN metastases. Of these 10 patients, isolated ipsilateral LN metastases were seen in 5 (50%) cases. Isolated contralateral LN metastases were seen in 3 (30%) cases, and bilateral metastases were seen in 2 (20%). CONCLUSIONS: In this cohort of patients with clinical stage I ovarian carcinoma with disease limited to one ovary, bilateral LN sampling increased the identification of nodal metastases. Ipsilateral sampling may result in the understaging of patients. Bilateral pelvic and paraaortic LN sampling is recommended to accurately stage ovarian carcinoma.

Aorta, Abdominal↗
PubMed2000

Ovarian carcinoid: management of primary and recurrent tumors.

We present a case of Stage I ovarian carcinoid tumor recurrent in the peritoneal cavity and review the pertinent literature concerning the management of this disease. Based on the data in the gynecologic and general surgery literature, it appears that primary complete cytoreductive surgery usually affords a high cure rate. Reexploration and attempt at complete resection of this slow-growing tumor appears to provide significant and prolonged palliation and is indicated for recurrent disease.

Carcinoid Tumor↗
PubMed1999

Colony-stimulating factor-1 and its receptor do not have a role in the pathogenesis of uterine sarcomas.

OBJECTIVE: Several studies have demonstrated overexpression of the mononuclear phagocytic growth factor colony-stimulating factor-1 (CSF-1) and its receptor (CSF-1R) in breast, ovarian, and endometrial adenocarcinomas, and their expression in each of these cancers is strongly correlated with poor prognosis. In addition to adenocarcinomas, sarcomas that are highly malignant arise at much lower frequency in the uterus. Given the common organ of origin and hormonal environment of the adenocarcinomas, we evaluated the potential role of CSF-1 and CSF-1R in the genesis of these tumors using immunohistochemical methods. RESULTS: Immunohistochemical analysis was performed on 19 archival uterine sarcoma samples. Affinity-purified rabbit anti-CSF-1 antiserum (R52) and human cross-reactive murine anti-c-fms antibody were used. In the 19 cases evaluated for CSF-1 immunoreactivity, 42.1% had staining in less than 25% of the tumor, 36.9% had staining in 25-50% of the tumor, and only 21% had staining in greater than 50% of the tumor. When present, the majority of the CSF-1 immunostaining was associated with the extracellular matrix. There was variable intensity in CSF-1 expression: 52.6% had negative to mild staining, and 47.4% had moderate to strong staining. Immunostaining for the CSF-1R revealed that 52.6% of tumors had expression in less than 25% of cells, 21.0% had expression in 25-50% of the tumor, and 26.4% had staining in greater than 50% of the tumor. There was variable intensity of CSF-1R staining. Slight staining was found in 31.6% of the cases, moderate staining was found in 47.4% of the tumors, and 21.0% of the cases had strong expression. There was no statistically significant correlation between CSF-1 and CSF-1R expression and stage, estrogen/progesterone receptor status, number of mitoses per 10 high-power fields, or disease outcome. In addition, overall expression and intensity of CSF-1 and CSF-1R did not predict tumor virulence or disease outcome. CONCLUSION: In contradistinction to endometrial adenocarcinomas, in which CSF-1/CSF-1R is strongly correlated with tumor progression, CSF-1 and CSF-1R overexpression does not appear to play a role in the growth and differentiation of uterine sarcomas.

Female↗
PubMed1999

Malignant Brenner tumor mimicking a primary squamous cell carcinoma of the cervix.

An 86-year-old female presented with a necrotic cervical mass that was biopsy-proven squamous cell carcinoma. She had an elevated CA-125 and a pelvic mass. At surgery, this mass was found to be of adnexal origin and contiguous with the cervix. Histology showed a malignant Brenner tumor with abundant squamous differentiation eroding the cervix and simulating a primary cervical malignancy. We describe this case and review the literature on metastatic tumors to the cervix.

Aged↗
PubMed1998

The rectus abdominis myocutaneous flap: modifications, complications, and sexual function.

BACKGROUND: Vaginal, perineal, and pelvic floor reconstruction is being performed with increasing frequency in conjunction with radical pelvic surgery. Although the vertical rectus abdominis myocutaneous flap is ideally suited to such procedures, little information exists regarding risks or complications associated with it. METHODS: A chart review of all patients who underwent this procedure at two institutions was performed, and the results were compared with existing series. Surviving patients were asked to describe their satisfaction with the procedure and their sexual function. RESULTS: Between 1990 and 1997, 22 patients underwent placement of a rectus abdominis myocutaneous flap for vaginal/pelvic floor reconstruction, 21 (95.5%) at the time of pelvic exenteration. Attachment of the graft was complete in 20 patients (90.9%) and partial in 1 (4.5%), and 1 patient experienced complete loss that resulted in total vaginal stenosis. Four patients (18.2%) developed mild vaginal stenosis that was corrected with dilators. Donor site complications included wound separation (above the fascia) in three patients and one delayed abdominal closure. There were no cases of bowel obstruction, dehiscence, hernia, or death. The only statistically significant identifiable risk factors for graft necrosis included prior abdominal surgery and operative time. Thirteen of 22 (59.1%) of the patients are cancer free (median progression free interval, 42.2 months), 11 (84.6%) of whom reported having had vaginal intercourse since surgery. CONCLUSIONS: The rectus abdominis myocutaneous flap can be safely used with excellent results and acceptable morbidity, and in this series it restored sexual function in the majority of cancer survivors. Because previous abdominal surgery (transverse incisions or colostomy) may compromise blood supply to the flap, alternative sites should be considered in such cases.

Adult↗
PubMed1997

Pelvic exenteration for cervix cancer: would additional intraoperative interstitial brachytherapy improve survival?

OBJECTIVE: Improved local control with the addition of brachytherapy to pelvic exenteration for recurrent cervical cancer has been reported to improve survival. We examined the sites of recurrence after pelvic exenteration to determine if these patients might have been salvaged by the improved local control promised by interstitial brachytherapy. We sought to identify risk factors available intraoperatively or perioperatively which might predict decreased local control. METHODS: A retrospective review of 26 patients with recurrent cervical cancer who underwent total pelvic exenteration since 1988 at our institution was performed. RESULTS: Overall, the mean follow-up was 29.5 months (range 6.1-81.6). Of the 26 patients, 14 had no evidence of disease (NED), 1 was alive with disease (AWD), 9 were dead of disease (DOD), and 2 died of unrelated causes (DOC). Seven of 26 patients (27%) had margins < or = 5 mm, of whom 2 were NED, 4 DOD, and 1 AWD. Seven of 26 (27%) patients had lymphovascular involvement (LVI) or perineural invasion (PNI) with clear margins. Three of the seven with LVI or PNI and clear margins were NED, and four DOD. Of the 10 failures, 9 (90%) had close margins, PNI, or LVI. CONCLUSION: Our data reveal that 9 of 14 (64%) patients with close margins, LVI, or PNI were DOD or AWD, and 6 of 9 of those patients suffered local regional failure alone. Brachytherapy has the potential to cure 6 of 14 (43%) patients with these risk factors. Further study of brachytherapy at the time of pelvic extenteration is warranted.

Adult↗
PubMed1997

Continuous low-dose combined hormone replacement therapy and the risk of endometrial cancer.

Hormone replacement therapy (HRT) provides relief of menopausal symptoms, reverses atrophic urogenital changes, prevents osteoporosis, and produces favorable lipoprotein effects. Continuous combined HRT using 2.5 mg of medroxyprogesterone was designed to increase patient compliance by eliminating withdrawal bleeding while at the same time retaining the beneficial effects of HRT. There are limited long-term data, however, regarding the safety of continuous combined HRT. Of concern are reports of endometrial carcinoma arising in women receiving continuous HRT with low-dose progestin. Eight cases of women who developed endometrial carcinoma while on this regimen are presented. The possible increased risk of endometrial cancer associated with this regimen may be related to inadequate progestin dose, prior use of unopposed estrogen, poor patient compliance, use of less effective progestins, less efficient reversal of hyperplasia, and the use of progestin continuously.

Aged↗
PubMed1997

Endometrioid adenocarcinoma of the ovary and long-term tamoxifen therapy: a coincidence or a cause for concern?

In recent years, the extensive usage of tamoxifen in patients with breast cancer has led us to acquire a great deal of knowledge of its effects on various organs in the gynecological system, especially the effect on the endometrium and the increased risk of endometrial cancer. Information on the possible potential carcinogenic effect of tamoxifen on the ovary, however, has been limited, mainly because of the overall low incidence of ovarian carcinoma. In addition, there is the confounding variable posed by the diverse here-ditary breast and ovarian cancer syndromes which tend to occur in a younger age group. Here, we present a case of a postmenopausal woman who was treated for six years with tamoxifen for breast cancer before being diagnosed with endometrioid carcinoma of the ovary. We believe that given the age of the patient and the duration of tamoxifen use, the occurrence of ovarian endometrioid carcinoma may be associated with long-term tamoxifen use.

Aged↗
PubMed1997

Induction of transforming growth factor beta-1 in cervical intraepithelial neoplasia in vivo after treatment with beta-carotene.

Transforming growth factor (TGF) beta1 is a potent growth inhibitor of epithelial cells. Loss of responsiveness to TGF-beta1 and/or loss of TGF-beta1 itself may be important in the progression of cervical intraepithelial neoplasia to invasive cervical cancer. Retinoids have antiproliferative effects on epithelial cells and have been used as chemopreventive and chemotherapeutic agents for several human cancers. There is evidence that retinoids exert their effects by promoting the induction of TGF-beta. The aim of this study was to determine whether the expression of TGF-beta1 was altered in patients enrolled in a clinical trial designed to test the therapeutic efficacy of beta-carotene, a carotenoid metabolized to retinol, in cervical intraepithelial neoplasia. Using an immunohistochemical technique, tissues were stained with two types of antisera that react with the intracellular and extracellular forms of TGF-beta1. Matched cervical biopsies taken from 10 patients before and after treatment with beta-carotene were immunostained simultaneously to allow direct comparison of relative staining intensity. A significant increase in intracellular TGF-beta1 immunoreactivity was noted in cervical epithelial cells in patients with cervical intraepithelial neoplasia after treatment with beta-carotene (P = 0.003). These results demonstrate regulation of a TGF-beta isoform in vivo in humans in response to beta-carotene administered as a chemopreventive agent.

Chemoprevention↗
PubMed1996

Altered expression of transforming growth factor-beta 1 in cervical neoplasia as an early biomarker in carcinogenesis of the uterine cervix.

BACKGROUND: Transforming growth factor-beta 1 (TGF-beta 1) is a potent growth inhibitor of epithelial cell growth, but can also stimulate stromal cell growth. Loss of responsiveness to TGF-beta 1 or loss of TGF-beta 1 itself may be important in the progression of cervical intraepithelial neoplasia (CIN) to invasive cervical carcinoma. METHODS. To examine the expression of TGF-beta in early stages of malignant transformation of the uterine cervix, paraffin embedded tissue samples from 11 patients with normal cervical epithelium, 15 with CIN I-III, 12 with microinvasive, and 18 with invasive squamous cell carcinoma were examined using an immunohistochemical technique. Tissues were immunostained with polyclonal antibodies that react with intracellular and extracellular forms of TGF-beta 1. RESULTS: Percent positive staining for the intracellular form of TGF-beta 1 was 100% for normal epithelium, 73.3% for CIN, and 44.1% for invasive carcinomas, (P = 0.002). Percent positive staining for the extracellular form of TGF-beta 1 was 63.6% for stroma underlying normal epithelium, 60% for stroma associated with CIN, and 94.1% for stroma surrounding invasive cancer (P = 0.007). CONCLUSIONS: Decreased expression of intracellular TGF-beta 1 in neoplastic epithelium and increased expression of extracellular TGF-beta 1 in stroma associated with invasive cervical carcinoma suggest that an early event in the neoplastic transformation of cervical epithelia] cells may involve the loss of TGF-beta 1. Tumor progression may be indirectly promoted by TGF-beta 1 secreted into or produced by supporting stromal elements.

Biomarkers, Tumor↗
PubMed1996

Mature results of a phase II trial of concomitant cisplatin/pelvic radiotherapy for locally advanced squamous cell carcinoma of the cervix.

PURPOSE: Patients with locally advanced squamous cell carcinoma of the cervix have a poor prognosis when treated by standard radiotherapy (RT) alone. Factors such as large tumor volume or nodal disease result in pelvic and distant treatment failures. Cisplatin (CDDP), a known radiosensitizer with documented activity in squamous cell carcinomas, was used in a phase II prospective study to evaluate the efficacy of combined chemo/radiotherapy in locally advanced squamous cell carcinomas of the cervix. METHOD: CDDP was administered (20 mg/m2) daily X 5 at 21-day intervals with concomitant external beam and intracavity RT. Standard RT was delivered at 1.8-2.0 Gy/day, 5 fractions per week for 5 weeks. Intracavitary cesium insertions were planned to treat point A to approximately 80 Gy. RESULTS: Fifty-nine patients were enrolled from March 1986 to July 1990. Four patients were voluntarily withdrawn, leaving 55 patients evaluable for response. Of these, 16 were Stage IB/IIA, 11 were Stage IIB, 24 were Stage III, and 4 were Stage IV. The median age of patients enrolled was 47 years (range 27-79). Median follow-up time was 65 months (range 60-113). Histopathologic confirmation of node status was available in 33 patients, of whom 45.5% (15/33) had nodal metastases. Overall response was 96% (CR = 87%, PR = 9.0%) and 3.6% had progressive disease during treatment. Forty-six patients were evaluable at 5 years for overall and disease-free survival. Calculations were based on Kaplan-Meier product limit estimates. The 5-year survival was 73% for Stage IB/IIA, 60% for Stage IIB, 67% for Stage III, and 25% for Stage IV. The disease-free survival at 5 years was 73% for Stage for IB/IIA, 50% for Stage IIB, 67% for Stage III, and 25% for Stage IV. Hematologic toxicity was severe but tolerable. No treatment-related deaths occurred. CONCLUSION: Concomitant CDDP/RT is a safe and tolerable method of treating patients with locally advanced squamous cell carcinoma of the cervix. Our data suggest a benefit in both disease-free and 5-year survival, particularly notable among patients with Stage III disease.

Adult↗
PubMed1996

Pregnancy and cervical infection with human papillomaviruses.

OBJECTIVE: This investigation was undertaken to assess whether pregnancy represents a risk factor for human papillomavirus (HPV) infection which is independent of age and other known HPV risk factors. METHODS: One hundred eighty-nine women were enrolled from the outpatient clinics of a large municipal hospital. The subjects completed a self-administered questionnaire and underwent a gynecological examination which included a cervicovaginal lavage. Lavage samples were assessed for the presence of HPV DNA by restriction enzyme analysis and Southern blot hybridization. Statistical significance was assessed by the chi 2-test. Logistic regression was used to assess the association between pregnancy and HPV while controlling for the effect of other risk factors. RESULTS: The prevalence odds ratio (POR) for the association of pregnancy and HPV infection was 2.2 (95% C.I. 1.1-4.5). The prevalence of HPV increased with increasing gestational age (HPV prevalence of 18.9% among non-pregnant women vs. 27.3% in those in the first 12 weeks of pregnancy and 39.7% in those who were past the 12th week of pregnancy). Although statistical significance was not achieved in a multivariate model which controlled for age, race/ethnicity, education, age at first coitus, number of sexual partners within the last year and parity, the POR associated with the current pregnancy (POR = 2.1) was not substantially changed by correcting for these risk factors, suggesting that these factors were not significant confounders of the association between pregnancy and HPV infection. CONCLUSION: Current pregnancy is associated with a modestly increased prevalence of cervical HPV infection. This association appears to be independent of age and other major HPV risk factors.

Adolescent↗
PubMed1996

Laparoscopic surgery in patients with a ventriculoperitoneal shunt. A case report.

BACKGROUND: Ventriculoperitoneal shunts have afforded many patients the opportunity to expect a normal lifespan. Since laparotomy is more likely to be associated with adhesion formation, potentially reducing the functional capacity of ventriculoperitoneal shunts, laparoscopy may be a preferable surgical alternative. CASE: A 64-year-old woman presented with a pelvic mass requiring surgical evaluation to rule out ovarian cancer. She had a ventriculoperitoneal shunt. Diagnostic laparoscopy was performed without complication. However, due to the significant adhesions from previous surgery, the mass could not be safely evaluated, and the procedure was completed by laparotomy. CONCLUSION: This is the first report of laparoscopy for a pelvic mass in an adult with a ventriculoperitoneal shunt. Laparoscopy is preferable to laparotomy for the replacement or repair of ventriculoperitoneal shunts. Also, laparoscopy should be considered for other problems requiring surgical intervention.

Female↗
PubMed1996

Squamous cell carcinoma in mature cystic teratoma in a young woman: a diagnostic and management dilemma.

Mature cystic teratomas of the ovary are one of the most common ovarian neoplasms found in reproductive age women. The most common type of malignancy associated with ovarian mature cystic teratomas is squamous cell carcinoma. The frequency of this type of malignant degeneration is age related and is most common in the fifth and sixth decade of life. A case of a squamous cell carcinoma which developed in a mature cystic teratoma in a 25-year-old female is presented and issues regarding the diagnosis and management of this rare complication are discussed.

Adult↗
PubMed1996

Plasma levels of beta-carotene, lycopene, canthaxanthin, retinol, and alpha- and tau-tocopherol in cervical intraepithelial neoplasia and cancer.

Epidemiological studies continue to identify an association of dietary antioxidant micronutrients in cancer prevention. A number of case-control and cohort studies have demonstrated a relationship between high intake of foods rich in carotenoids, tocopherols, and vitamin C with a reduced risk of certain human malignancies. The purpose of this study was to investigate the comparative plasma levels of a profile of known dietary antioxidants, namely, beta-carotene, lycopene, canthaxanthin, retinol, alpha-tocopherol, and tau-tocopherol. The target population was women with a histopathological diagnosis of cervical intraepithelial neoplasia (CIN) or cervical cancer and a control group. All women resided in the same catchment area (Bronx Borough, New York City) and were of similar inner-city socioeconomic backgrounds representing a fairly homogenous population group. A cross-sectional sample of 235 women was recruited with informed consent. Plasma nutrient levels were measured by reverse-phase high pressure liquid chromatography under study codes. The mean plasma levels of carotenoids (beta-carotene, lycopene, and canthaxanthin), as well as alpha-tocopherol, were significantly lower in women with CIN and cervical cancer. In contrast, the mean plasma level of tau-tocopherol was higher among patients with CIN, while the mean plasma level of retinol was comparable among the groups. There were significant linear trends for all three carotenoids and quadratic trends for alpha- and tau-tocopherol with the degree of cervical histopathology. Plasma beta-carotene concentrations in cigarette smokers were significantly lower regardless of cervical pathology, whereas plasma lycopene and canthaxanthin levels were significantly lower in smokers with CIN. The findings of a decrease in all plasma antioxidant nutrient levels except tau-tocopherol in women with CIN and cancer suggest a potential role for antioxidant deficiency in the pathogenesis of CIN and carcinoma of the cervix, which requires further investigation.

Adult↗
PubMed1996

Analysis of MDR1 expression in normal and malignant endometrium by reverse transcription-polymerase chain reaction and immunohistochemistry.

The purpose of this study was to quantitate the expression of human MDR1 mRNA levels in normal endometrium and in endometrial carcinoma and to determine the association of MDR1 levels with prognostic indicators. Endometrial samples from 43 postmenopausal patients with endometrial carcinoma and 38 patients (controls) with benign disease undergoing hysterectomy were snap-frozen. MDR1 levels were determined by quantitative reverse transcription-PCR (RT-PCR) and compared to sensitive and resistant cell lines. Immunohistochemistry was done with MM4.17, an anti-MDR1 antibody, on paraffin sections, and the results were compared to those obtained from RT-PCR. Data was analyzed using the Kruskal-Wallis and Bonferroni tests, setting the P value at 0.05. In both postmenopausal endometrial tissue and tumors, MDR1 expression was localized to the epithelial cell layer. Comparison of immunohistochemistry and RT-PCR results demonstrated a correlation of 80%. In control patients, MDR1 expression was significantly higher in postmenopausal endometrium (n = 15) than in the proliferative premenopausal endometrium (n = 15; P = 0.0024). MDR1 expression in all tumors was lower than that measured in the postmenopausal controls. Between each tumor group, there was no significant difference in the MDR1 levels observed. MDR1 expression was significantly lower in patients with high nuclear grade (n = 18) tumors when compared to patients with low nuclear grade (n = 14; P = 0.04) tumors. Comparison of MDR1 levels with multiple prognostic indicators for endometrial cancer was only significant for nuclear grade. The data indicate that MDR1 expression is not a major component of the drug resistance observed in primary endometrial tumors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Promising new therapies in the treatment of advanced ovarian cancer.

Advanced stage ovarian cancer is the most lethal gynecologic cancer. Despite initial response rates of 60-80% with platinum-based chemotherapy, more than 75% of women with this malignancy die of complications associated with this disease. There is a pressing need to find new chemotherapeutic agents for patients with advanced ovarian cancer. Phase II studies have identified paclitaxel as the most active drug in ovarian cancer since the introduction of cisplatin in the 1970s. Phase III studies will define the role of paclitaxel as initial therapy. Camptothecins (topotecan, CPT-11, 9-amino-camptothecin) inhibit topoisomerase I. CPT-11 and topotecan have shown activity in Phase II trials. Gemcitabine, a pyrimidine antimetabolite, has shown activity in Phase II trials. Other promising drugs (docetaxel, treosulfan) are under investigation. Modulation of drug resistance is being explored in Phase I/II studies. Clinical trials have been initiated with buthionine-sulfoximine, an inhibitor of glutathione biosynthesis, which decreases the ability of resistant cells to inactivate platinum compounds and alkylating agents. Cyclosporin has been shown to increase cisplatin cytotoxicity. Phase I trials have demonstrated the feasibility of combining cyclosporin and cisplatin. Phase II trials of cyclosporin analogs (PSC 833) and paclitaxel in refractory ovarian cancer are ongoing. Promising leads in drug development should provide new therapies for patients with ovarian cancer. Further research in the modulation of drug resistance may identify new mechanisms or strategies with which to prevent the emergence of drug resistance.

Antineoplastic Agents↗