Biomedical subjects

M S Piver

Publications and source records attributed to M S Piver.

At least 37 records · Page 2Linked to original sources

PubMed1999

Laparoscopic management of women with a family history of ovarian cancer.

BACKGROUND AND OBJECTIVE: The safety of laparoscopic surgery in women with a family history of ovarian cancer predicted to have benign disease has not been established. The objective of this study was to evaluate the feasibility and complications of operative laparoscopy and to describe the pathologic findings in this patient population. METHODS: Sixty-two consecutive women with a family history of ovarian cancer who elected prophylactic oophorectomy or had predicted benign adnexal disease were offered laparoscopic surgery. Patient characteristics, details of laparoscopic surgery, operative and postoperative complications, and histopathologic findings were recorded. RESULTS: Laparoscopy was converted to laparotomy in 2 patients (3.2%); 1 patient (1.6%) had an operative vascular complication, and 1 patient (1.6%) had postoperative bleeding. Median (range) estimated blood loss, operative time, and hospital stay were 50 ml (50-1,500), 120 min (60-290), and 1 day (0-9), respectively. Histopathologic findings included normal ovaries (n = 20), corpus luteum cyst (n = 16), follicular cyst (n = 8), endometriotic cyst (n = 7), serous cystadenoma (n = 5), epithelial hyperplasia (n = 4), dermoid cyst (n = 1), and fibrothecoma (n = 1). CONCLUSIONS: Laparoscopic surgery is feasible and safe in women with a family history of ovarian cancer predicted to have benign disease and is associated with low blood loss and short hospital stay. Most ovaries removed are either normal or have benign disease.

Adult↗

PubMed1999

Role of salvage chemotherapy with topotecan and cisplatin in patients with paclitaxel- and platinum-resistant recurrent ovarian or primary peritoneal cancer: a phase II pilot study.

BACKGROUND AND OBJECTIVES: We assessed the role of salvage chemotherapy with topotecan and cisplatin in patients with platinum- and paclitaxel-resistant advanced and recurrent ovarian or primary peritoneal cancer, based on the reported in vivo and in vitro synergism between these two drugs. METHODS: Twenty patients were entered in this phase II trial from November 1997 to November 1998. They received cisplatin at 50 mg/m(2) on day 1 with topotecan at 0.6 mg/m(2) from day 1 to 5 every 28 days. In 70% of patients (14/20), this combination represented at least a third line of therapy. RESULTS: A clinical response rate of 13.3% (two partial responses) was obtained in the 15 patients with evaluable disease. Sixty percent of patients (9/15) had stable disease and 26.7% (4/15) had progression. The median progression-free interval and survival were 4 months and 7 months, respectively. The 20 patients evaluable for toxicity received a mean of four chemotherapy cycles. Dose reductions were required in 45% of patients despite the administration of growth factors. The major dose-limiting toxicity was a 50% occurrence (10/20) of grade 4 thrombocytopenia and 30% (6/20) grade 4 neutropenia. There was one septic death. CONCLUSIONS: These data suggest that combination therapy with topotecan and cisplatin has minimal activity in platinum- and paclitaxel-resistant advanced and recurrent ovarian or primary peritoneal cancer at the doses utilized in this trial.

Adult↗

PubMed1999

Characterization of human ovarian carcinomas in a SCID mouse model.

This study characterizes a murine model which is promising for the study of the growth and natural history of ovarian cancer and for testing of new therapies for its treatment. Intact portions of 20 different human ovarian cancer surgical specimens were implanted in over 60 severe combined immunodeficient (SCID) mice using techniques previously developed in our laboratory. Growth of xenografts was evaluated by gross examination and histopathologic analysis. Confirmation of the human origin of the tumor outgrowth was obtained using in situ hybridization analysis. By histological evaluation, all of the patients' tumors showed evidence of invasive growth in at least 1 of the mice implanted with portions of each surgical specimen and these tumors remained morphologically similar to the parent tumors for a long period of time. Furthermore, 65% (13/20) of the xenografts grew rapidly enough (i.e., reached a diameter of 1-2 cm within 2-6 months) to allow passage to subsequent SCID mice. Among the passaged xenografts, 3 eventually developed metastases in a distribution pattern similar to that of naturally occurring ovarian cancer and 2 developed ascites without evidence of further metastatic spread. Upon evaluation of sera from tumor-bearing mice, human antibodies presumably derived from immunoglobulin-secreting cells present in the original tumor specimen were identified. In support of this, human B cells and plasma cells could be seen within the tumor xenograft for more than 6 months following implantation. In summary, transplantation of surgical specimens from ovarian cancer patients into SCID mice results in an attractive model for the study of the natural history of ovarian cancer and may also be useful for analysis or new experimental therapeutic approaches for the treatment of this disease.

Animals↗

PubMed1999

Effects of IL-12 on human ovarian tumors engrafted into SCID mice.

OBJECTIVE: The effects of murine interleuken (IL)-12 on the growth of surgical specimen-derived malignant human ovarian tumors engrafted in severe combined immunodeficient (SCID) mice were assessed. The SCID mouse model facilitated the evaluation IL-12's effect on the host innate immune response against human ovarian cancer xenografts. METHODS: Equal portions of specimen-derived human ovarian carcinoma were engrafted subcutaneously into SCID mice. After 7 days, mice were placed into one of two treatment groups: (1) placebo/control or (2) murine IL-12 (0.33 mcg/day intraperitoneally x 20 days). Anti-asialo GM1 was administered on day 0 to 3 mice from the IL-12-treated group. Serial tumor volumes were measured. On day 21, mice from each group were sacrificed, and tumors and spleens were evaluated. Data analysis included chi2 tests, Student t tests, and analysis of variance when appropriate. The entire experiment was repeated for a total of three times with similar results. A total of 45 mice and two different human tumor specimens were utilized. Representative data were reported. RESULTS: IL-12 resulted in mean tumor growth delay and regression when compared to controls (P = 0. 02). Among the IL-12 group, 22% (2/9) developed complete remissions. When anti-asialo GM1 was added prior to IL-12, no tumor growth delay was noted. Splenic weights were higher among IL-12-treated mice compared to controls (P < 0.01). Spleen sections demonstrated expanded white pulp among IL-12-treated mice compared to controls. Histologic evaluation of tumor sections revealed central necrosis among tumors from mice treated with IL-12. Immunohistochemical stains identified increased numbers of NK cells in clusters within tumors from mice treated with IL-12 whereas NK cells were found to be sparsely scattered in control tumors. CONCLUSIONS: Murine IL-12 treatment resulted in significant tumor growth delay and tumor regression in SCID mice engrafted with human ovarian cancer. The data support an immunologic basis for the observed anti-tumor effects and suggest a role for NK cells as part of the effector pool. The current data support the clinical evaluation of IL-12 in the treatment of epithelial ovarian cancer.

Adjuvants, Immunologic↗

PubMed1999

Effects of recombinant human erythropoietin on the antitumor effect of cisplatin in SCID mice bearing human ovarian cancer: A possible oxygen effect.

PURPOSE: Experiments were designed to evaluate the effect of an elevated hematocrit using recombinant human erythropoietin (Epo) on the antitumor response of cisplatin on human ovarian cancer engrafted in mice. METHODS: Forty female severe combined immunodeficient (SCID) mice with large human ovarian cancer xenografts implanted on the gonadal fat pad (GFP) and 40 female SCID mice with small subcutaneous (sq) human ovarian cancer xenografts were placed in one of four treatment groups. Group 1 (controls) received phosphate-buffered saline injections. Group 2 (Epo group) received Epo at 20 units three times per week. Group 3 (cisplatin group) received cisplatin at 5 mg/kg/week. Group 4 (Epo + cisplatin group) received Epo and cisplatin as above. Cisplatin was administered on day 0 for mice bearing large GFP tumors and was injected on days 0 and +7 for mice bearing small sq tumors. Epo injections were started on day -15 and continued until the completion of the experiment. Evaluations of the tumor growth, hematocrits, and performance status were made. The experiments were repeated in 24 SCID mice bearing small sq tumor xenografts with similar results. Representative data were reported. RESULTS: Among mice bearing large GFP tumors, a tumor growth delay was noted in the groups that received cisplatin with or without Epo compared to controls (P < 0.05). However, significant tumor growth delay could not be reached for mice in the Epo + cisplatin group compared to the cisplatin group (P = 0.07). Among mice bearing small sq tumors, a significant improvement in tumor regression was achieved in the Epo + cisplatin group compared to the cisplatin group (P < 0.05). No difference in tumor growth resulted in the Epo group compared to controls. Epo resulted in a 25-35% increase in the hematocrit in both the Epo group and the Epo + cisplatin group (P < 0.01). Mice in the control and in the Epo groups remained healthy. Mice treated with cisplatin developed objective signs of morbidity; however, performance scores for mice in the Epo + cisplatin group remained lower than scores in the cisplatin group. CONCLUSIONS: The data demonstrate a cisplatin-sensitizing effect on human ovarian cancer in SCID mice induced by the pretreatment elevation and maintenance of the hematocrit using Epo. These findings are consistent with an oxygen sensitization of cisplatin. Corroboration of these results may have significant clinical implications for the treatment of solid tumor patients.

Animals↗

PubMed1999

Epidemiologic differences between women with borderline ovarian tumors and women with epithelial ovarian cancer.

OBJECTIVE: The aim of this study was to study the relationship between borderline ovarian tumors (BLOT) and epithelial ovarian cancer (EOC) by comparing the epidemiologic features of women with BLOT with those of women with EOC of similar histology. MATERIAL AND METHODS: The epidemiologic features of 32 women with serous and mucinous BLOT were compared with those of 273 women with primary serous or mucinous EOC. We included all women with the documented respective histologic diagnoses admitted to Roswell Park Cancer Institute between 1982 and 1996 who returned a self-administered epidemiologic questionnaire which contained 44 items pertaining to reproductive, contraceptive, medical, social, dietary, occupational, and family histories of cancer. Individual variables between both groups were compared using the Student t test, chi2 analysis, the Mantel-Haenszel test, and the Wilcoxon nonparametric test. Two-tailed P < 0.05 was considered significant. RESULTS: The response rate to the questionnaire was 63% in the BLOT group and 60% in the EOC group. There was no significant difference between the two groups in geographic location, race, education, income, smoking, marital status, age at first pregnancy, age at first birth, history of hysterectomy, history of infertility, history of tubal surgery, use of hormone replacement therapy, or history of diaphragm or intrauterine contraceptive device use. There were no significant differences in family history of malignancy between women with BLOT and those with EOC. Women with BLOT were significantly younger than those with EOC (mean age 47 +/- 14.0 versus 56 +/- 13.7, P < 0.01). There was an apparent difference in oral contraceptive pill use between both groups. However, when we adjusted for age by stratification this difference was not significant (P = 0.089). CONCLUSIONS: The epidemiologic features of women with BLOT are similar to those of women with EOC with the exception of an earlier age of onset. These findings might be consistent with one etiology for both conditions.

Adenocarcinoma, Mucinous↗

PubMed1999

Analysis of failed and complicated laparoscopy on a gynecologic oncology service.

OBJECTIVE: To assess the incidence of and factors that predict failed or complicated operative laparoscopy on a gynecologic oncology service. METHODS: Two hundred four consecutive operative laparoscopies were reviewed. Procedures converted to laparotomy or associated with major operative or postoperative complications were compared with uncomplicated laparoscopies with respect to patient characteristics, details of operative procedure, and length of hospitalization. The influence of patient characteristics, operative findings, and specific procedures on the risk of failed or complicated laparoscopies was estimated. RESULTS: Twenty-five (12. 3%) procedures were either converted to laparotomy or associated with major operative or postoperative complications. Women with failed or complicated laparoscopies had significantly more previous laparotomies and adhesions, greater blood loss, and longer hospital stay than those with uncomplicated laparoscopies (60.0% vs 35.7%, P = 0.03, 68.0% vs 37.4%, P<0.001, 275 ml vs. 132 ml, P = 0.03; and 5. 9 days vs 0.98 days, P< 0.001, respectively). Age, body mass index, parity, menopausal status, preoperative CA-125, appearance of adnexal masses, and complexity of the procedure had no significant influence on failed or complicated laparoscopies. In univariate analysis, history of laparotomy and presence of adhesions and in multivariate analysis only presence of adhesions were predictive of failed or complicated laparoscopies (P = 0.03, <0.001, and 0.006, respectively). CONCLUSIONS: The incidence of failed and complicated laparoscopy is low on a gynecologic oncology service. Presence of adhesions is the only significant independent risk factor predictive of failed or complicated laparoscopy.

Adult↗

PubMed1999

First-line chemotherapy with paclitaxel and platinum for advanced and recurrent cancer of the cervix--a phase II study.

OBJECTIVE: The aim of this study was to assess the role of first-line chemotherapy with paclitaxel and platinum in the treatment of advanced or recurrent cervix cancer. METHODS: Twenty patients with advanced or recurrent cancer of the cervix with no prior chemotherapy and measurable disease were entered in a phase II trial from September 1995 to September 1998. Seventeen patients were treated with paclitaxel at 135 mg/m(2) over 24 h followed by cisplatin at 75 mg/m(2) every 4 weeks. Three patients with impaired renal function were treated with paclitaxel at 135 mg/m(2) over 3 h with carboplatin at 300 mg/m(2). RESULTS: A clinical response rate of 45% was noted (two complete responses and seven partial responses) with a median duration of 6 months (range: 1.5-9). The median progression-free interval and overall survival in patients with a clinical response was 10.5 and 13 months, respectively, compared to 4 (P = 0.015) and 6 months in the nonresponders (P = 0. 14). Seven of nine patients (77.8%) with a clinical response are alive. Patients with recurrences outside the radiation field had twice the response rate (60%) than that of those within the radiated field. The chemotherapy was well tolerated; the most significant toxicity was grade 3/4 neutropenia (55%). No patient had discontinuation of chemotherapy due to toxicity. CONCLUSIONS: First-line chemotherapy with paclitaxel and platinum for advanced and recurrent cervix cancer is promising and deserves consideration for large phase III trials.

Adult↗

PubMed1999

Prognostic significance of p53 and p21(waf1/cip1) immunoreactivity in epithelial cancers of the ovary.

OBJECTIVES: Theprognostic value of p53 expression in epithelial ovarian cancer remains unresolved. We hypothesized that prognosis may relate more to expression of p21(waf1/cip1), the major downstream effector of p53, which can also be induced through p53-independent mechanisms. We therefore studied the relationship of p53 and p21(waf1/cip1) expression in epithelial ovarian cancers to clinicopathological variables and prognosis. METHODS: Fixed, embedded tumors from 85 patients with untreated, primary epithelial ovarian cancer were immunostained with antibodies to p53 and p21(waf1/cip1). Expression was correlated with clinicopathological features and prognosis. Survival curves were calculated by the Kaplan-Meier method and compared using the log-rank test for p53, p21(waf1/cip1), and all combinations of expression of the two markers. RESULTS: Sixty-two percent of tumors expressed p53, and 42% expressed p21(waf1/cip1). There was no correlation between p53 and p21(waf1/cip1) expression. Advanced stage, grade, age >/=50, and p53 expression were associated with worse disease-free survival. Patients whose tumors were p53(+)/waf1(-), however, had a particularly strong association with poorer disease-free survival when compared with other combinations of p53 and p21(waf1/cip1) expression (P = 0.003). Neither p53, nor p21(waf1/cip1), nor combinations of expression were independently related to survival when histology, age, stage, and differentiation were considered. CONCLUSIONS: p53 expression in the absence of p21(waf1/cip1) expression is a better marker of poor prognosis than either p53 or p21(waf1/cip1) expression status alone in univariate analysis. Absence of independent prognostic significance may be related to the paucity of early stage cases in the current study.

Cyclin-Dependent Kinase Inhibitor p21↗

PubMed1999

Perineal talc exposure and subsequent epithelial ovarian cancer: a case-control study.

OBJECTIVE: To evaluate the role of talcum powder use as a risk factor for the development of epithelial ovarian cancer. METHODS: In a case-control study, 499 patients with epithelial ovarian cancer were frequency matched for age at diagnosis (-5 years) with a control population of 755 patients. The odds ratio (OR) for the development of epithelial ovarian cancer was estimated using logistic regression analysis with adjustment for age at diagnosis, parity, oral contraceptive use, smoking history, family history of epithelial ovarian cancer, age at menarche, menopausal status, income, education, geographic location, history of tubal ligation, and previous hysterectomy. RESULTS: Two hundred twenty-one of 462 patients (47.8%) in the study population and 311 of 693 patients (44.9%) in the control population had ever used talcum powder (OR 0.92; 95% confidence interval [CI] 0.24, 3.62). A significant association between duration of talc use and development of epithelial ovarian cancer was not demonstrable for 1-9 years (OR 0.9; 95% CI 0.6, 1.5), for 10-19 years (OR 1.4; 95% CI 0.9, 2.2), or for more than 20 years (OR 0.9; 95% CI 0.6, 1.2). To eliminate the possible confounding variable of surgery for the management of ovarian cancer, we omitted 135 patients in the study population who underwent hysterectomy within 5 years of the diagnosis of ovarian cancer. Within this subgroup of patients, tubal ligation or hysterectomy among talc users still failed to demonstrate an increased risk for the development of ovarian cancer (OR 0.9; 95% CI 0.4, 2.2). CONCLUSION: A significant association between the use of talcum powder and the risk of developing epithelial ovarian cancer is not demonstrable, even with prolonged exposure.

Case-Control Studies↗

PubMed1999

Laparoscopic surgery in obese women.

OBJECTIVE: To assess the feasibility and complications of operative laparoscopy in women with high body mass indices (BMIs). METHODS: Forty-seven consecutive patients with BMIs exceeding 30 who underwent operative laparoscopy were compared with 160 consecutive patients with BMIs of 30 or less who underwent the same procedure. Patient characteristics, ultrasound features of adnexal masses, and details of operative procedures were compared. Operative and postoperative complications, the percentage of failed laparoscopies, and length of hospital stay were compared between groups. RESULTS: There were no significant differences between groups in terms of age, parity, menopausal status, history of laparotomy, ultrasound features of adnexal masses, complexity of laparoscopic procedures, and the presence and degree of adhesions at the time of laparoscopy. Estimated blood loss, operative times, operative and major postoperative complications, and lengths of hospital stay also did not differ significantly between women with high BMIs and those with low BMIs (180.3 versus 151.4 mL, P = .41; 150.5 versus 146.5 minutes, P = .78; 2.1 versus 1.9%, P = .90; 2.1 versus 1.9%, P = .91; and 2.3 versus 1.9 days, P = .51, respectively). However, women with BMIs exceeding 30 had a significantly higher incidence of procedure conversion to laparotomy (14.9 versus 5.6%, P = .04). CONCLUSION: Operative laparoscopy is safe and feasible in women with high BMIs. Although there is an increased chance of procedure conversion to laparotomy in these women, the morbidity and length of hospitalization associated with the procedure are similar to those among women with low BMIs.

Adolescent↗

PubMed1999

Altered surface and cyst epithelium of ovaries removed prophylactically from women with a family history of ovarian cancer.

Despite intensive investigation, the nature of epithelial ovarian cancer precursors remains controversial. Because women with a strong family history of ovarian cancer have a high probability of developing ovarian cancer themselves, ovaries removed prophylactically from such patients provide an opportunity to identify early neoplastic changes. Ovaries removed from 64 consecutive patients undergoing prophylactic oophorectomy and from 30 women with normal ovaries and no known family history of ovarian cancer were examined by light microscopy for a number of histopathologic features and by image cytometry for abnormalities of the cyst and surface epithelium. All analyses were performed without knowledge of the family history. Seven benign, but no tumors of low malignant potential or malignant epithelial tumors were found in the prophylactic oophorectomy group. There were more cortical inclusion cysts in the prophylactically removed than controls ovaries (P = .016), but no other architectural features differed between the two groups. No abnormalities were found in the surface or cyst epithelium in either group by light microscopy. In contrast, image analysis identified differences in the nuclei between the two groups, indicating that those from the surface epithelium of prophylactically removed ovaries were larger and contained more heterogeneously dense chromatin than those of controls, and that nuclei of the cyst epithelium had more irregular outlines. Ovarian epithelium from prophylactically removed ovaries exhibit abnormalities that are only identified by image analysis, and which might represent early preneoplastic changes. Such ovaries may be useful for identifying early molecular changes in ovarian cancer.

Adult↗

PubMed1999

Classification of IVS1-10T-->C as a polymorphism of BRCA1.

Mutations inactivating the tumor suppressor gene BRCA1 may be responsible for disease for up to 80% of familial ovarian cancer cases. In this syndrome, tumorigenesis classically initiates from an inherited mutation in one allele followed by somatic deletion of the normal allele. Sequencing of BRCA1 amplified from genomic DNA of lymphocytes and microdissected ovarian tumor cells of a familial ovarian cancer patient revealed three, rare heterozygous DNA variations (2418delA, 233G-->A, and IVS1-10T-->C) in both tumor and constitutional (lymphocyte) DNA. Thus, both copies of BRCA1 were retained in tumor. Haplotype analysis of the patient and four siblings assigned 2418delA to one copy of BRCA1 and 233G-->A and IVS1-10T-->C to the other. The DNA change, 2418delA, is considered a mutation that inactivated one BRCA1 allele because it caused a frameshift and generation of a premature stop codon, resulting in synthesis of a truncated peptide as evidenced by an in vitro protein truncation test. The DNA variation, 233G-->A, does not result in an amino acid change, and is considered a benign polymorphism. IVS1-10T-->C is a unique BRCA1 change that occurs in the last nucleotide of a consensus sequence for a branch site critical for RNA splicing. Therefore, we investigated whether IVS1-10T-->C deleteriously affected BRCA1 splicing or expression, and thereby inactivated the other BRCA1 allele. Using the technique of reverse transcription-polymerase chain reaction (PCR) with RNA isolated from lymphoid cell lines of the patient and of controls, no evidence was found that IVS1-10TC abnormally disrupted mRNA splicing or caused the absence of BRCA1 mRNA. Thus, IVS1-10T-->C is not harmful to BRCA1 function, and is classified a benign polymorphism. Retention of the normal BRCA1 allele in the tumor with the heterozygous germline BRCA1 mutation, 2418delA, indicated that mutational inactivation of both BRCA1 alleles was not required for tumorigenesis. It is possible that the normal allele may be functionally inactivated by a nonmutational mechanism.

BRCA1 Protein↗

PubMed1999

Gemcitabine salvage chemotherapy for patients with gynecologic malignancies of the ovary, fallopian tube, and peritoneum.

The efficacy and toxicity of gemcitabine salvage chemotherapy was evaluated in 27 heavily pretreated patients with recurrent and progressive ovarian, fallopian tube, or peritoneal cancer. At least one platinum-based chemotherapeutic regimen had failed in each patient. The median number of previous chemotherapy regimens and cycles of chemotherapy was 4 and 23, respectively. A total of 124 cycles of gemcitabine were delivered (median, 3 cycles). Hematologic toxicity included four patients with grade 3/4 thrombocytopenia and two patients with grade 3/4 neutropenia. Thrombocytopenia and neutropenia resulted in eight dose reductions and a single 1-week treatment delay. Nonhematologic side effects were well tolerated and largely self-limiting. No complete responses were observed. Three patients (11%) demonstrated partial responses to therapy. The duration of response was 7 months for two of the responders and 5 months for the third responder. Stable disease was observed in 14 patients (52%), in whom the median progression-free interval was 5 months. In conclusion, among heavily pretreated patients, gemcitabine has limited antitumor activity in platinum-resistant carcinomas of the ovary, fallopian tube, and peritoneum. The role of gemcitabine in the treatment of gynecologic malignancies of the ovary, fallopian tube, and peritoneum will be determined by studies that define the efficacy of multiagent regimens of chemotherapy that include gemcitabine and by studies that include patients who have been less heavily pretreated.

Adult↗

PubMed1999

p53, c-erbB, and Ki-67 expression in ovaries removed prophylactically from women with a family history of ovarian cancer.

Prophylactically removed ovaries from 64 women were compared with those from 30 women with no known family history of ovarian cancer for expression of the p53 tumor suppressor protein, the c-erbB-2 oncoprotein, and for the proliferation antigen Ki-67. All analyses were performed without knowledge of the family history. Ki-67 was expressed in rare nuclei in both the surface and cyst epithelial cells, whereas p53 was expressed in rare nuclei only in cyst epithelial cells. Neither the proportion of positive cases nor the intensity of staining differed between groups. c-erbB2 was not expressed in surface or cyst epithelium in any case from either group. Nuclei of granulosa and granulosa lutein cells expressed both Ki-67 and p53. In conclusion, increased expression of p53, c-erbB2, and Ki-67 was not found in the epithelium of prophylactically removed ovaries, suggesting that increased expression occurs later in the development of carcinoma or invasive tumor evolves too quickly to identify expression of these proteins in preinvasive epithelium.

Adult↗

PubMed1999

Expression of the hyaluronan receptor, CD44S, in epithelial ovarian cancer is an independent predictor of survival.

Most ovarian carcinomas present at advanced stage, principally as the result of dissemination to peritoneal sites. Standard CD44 (CD44S) is the principal receptor for hyaluronic acid, and in vitro and animal studies have suggested that the attachment of ovarian carcinoma cells to the peritoneal mesothelium involves the interaction between CD44S on ovarian carcinoma cells and hyaluronic acid on mesothelial surfaces. We, therefore, analyzed a series of ovarian carcinomas for the expression of CD44S by immunohistochemistry to see whether expression of this receptor by tumor cells correlated with clinicopathological factors and measures of patient outcome. Fifty-six fixed, paraffin-embedded primary epithelial ovarian tumors were immunostained with antibody to CD44S. Membrane staining was considered positive, and results were correlated with stage, grade, age, histology, and survival. Twenty-two (39%) tumors were positive for CD44S. There was no correlation between CD44 expression and histological type, grade, age, or stage. However, CD44 expression was significantly associated with survival in both univariate (P = 0.003) and multivariate (P = 0.006) analyses. These results support a role for CD44S expression in the spread of ovarian epithelial cancer and suggest that expression of this molecule is a significant independent predictor of survival in women with this disease.

Age Factors↗

PubMed1998

Laparoscopic-assisted application of interstitial brachytherapy for locally advanced cervical carcinoma: results of a pilot study.

PURPOSE: To assess the efficacy of diagnostic laparoscopy at the time of interstitial brachytherapy in patients with FIGO Stages IIB-IVA cervical carcinoma, who were not candidates for conventional brachytherapy after completion of whole pelvic radiation. MATERIALS AND METHODS: Six patients with FIGO Stages IIB-IVA cervical carcinoma completed whole pelvic radiation (WPR) and were assessed for the placement of conventional intracavitary brachytherapy. Three patients (Stage IIB) received 50.40 Gy WPR and three (Stage IIIA-VA) received 61.20 Gy WPR. Because distorted vaginal anatomy precluded the placement of standard intracavitary brachytherapy equipment, interstitial therapy was selected. To minimize the risk of source misplacement, needles were placed with laparoscopic guidance. 192Iridium was utilized as a source of radiation. RESULTS: A total of 98 needles were placed under direct laparoscopic guidance. The median interstitial brachytherapy tumor dose was 20.00 Gy (range 19.00-41.20 Gy). Eleven perforations in the pelvic peritoneum and/or bladder were identified intraoperatively in 5 of the 6 patients, leading to immediate repositioning of needles. No acute or short-term morbidity related to the procedure was appreciated. CONCLUSION: Interstitial brachytherapy offers an alternative for intracavitary radiation therapy for selected patients, in whom adequate placement of intracavitary afterloading equipment is precluded by abnormal pelvic geometry. Historically, the placement of interstitial sources has been a procedure that was performed without visualization of the pelvic cavity. A major concern is direct injury to pelvic viscera and intestine. The use of diagnostic laparoscopy at the time of placement of interstitial brachytherapy may avert potential complications from misapplication of interstitial sources. Longer follow-up is required to substantiate these results.

Adult↗

PubMed1998

Importance of lymph node metastases in primary peritoneal carcinoma.

BACKGROUND AND OBJECTIVES: The incidence and significance of lymph node involvement in patients with primary peritoneal adenocarcinoma (PPA) are unknown. The aim of the current study is to report on the incidence and significance of clinically or surgically detectable lymphadenopathy in women with PPA. METHODS: The study is a retrospective clinical review of patients with the confirmed diagnosis of PPA treated at Roswell Park Cancer Institute between 1982 and 1996. Patients with clinically or surgically detectable lymphadenopathy confirmed on histologic examination to be secondary to metastases from PPA were identified and compared to patients with negative lymph nodes with regard to clinicopathologic characteristics, treatment, response to treatment, and survival. RESULTS: Seventy-two patients with PPA were identified. Pelvic and periaortic lymph node biopsies or sampling were performed in 35% of the patients. In 8/72 patients (11%), lymphadenopathy was one of the presenting clinical or surgical findings. The clinicopathologic features, treatment, response to first-line chemotherapy, and estimated median overall survival were not different in patients with or without lymph node involvement (71.4% vs. 69.7%, P = 1.0, and 21.5 vs. 23.5 months, P = 0.14). CONCLUSIONS: Lymph node involvement is not an infrequent occurrence in patients with PPA and does not seem to be of adverse prognostic significance.

Adenocarcinoma↗