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Biomedical subjects

C D Runowicz

Publications and source records attributed to C D Runowicz.

At least 19 recordsLinked to original sources

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↗

Allelotype of papillary serous peritoneal carcinomas.

OBJECTIVE: Papillary serous peritoneal carcinoma (PSPC) is histologically indistinguishable from papillary serous ovarian carcinoma (PSOC) with a similar clinical presentation, yet may differ in its carcinogenesis. The purpose of this study was to determine the incidence of allelic loss and the frequency of p53 mutation by p53 overexpression in PSPC compared to PSOC. METHODS: An allelotype analysis of 26 patients with PSPC was performed using 39 microsatellite markers from 25 chromosomal arms. Thirty-seven previously studied patients with PSOC served as the comparison. P53 mutations were detected by immunohistochemical protein overexpression. RESULTS: There was significantly less LOH in PSPC than PSOC. Both the number of chromosomes with LOH and the proportion of tumors with allelic loss were less frequent. Significant LOH, defined as >/=30% of informative tumors having loss at a chromosome locus, was seen on 4 chromosome arms in PSPC: 12p, 17p, 17q, and 18q, compared to 18 arms in PSOC: 4q, 5q, 6p, 6q, 9p, 9q, 12p, 12q, 13q, 15q, 16q, 17p, 17q, 18q, 19p, 19q, 22q, and Xq (P < 0.001). The median LOH frequency was higher in PSOC than PSPC, 43% versus 33%, respectively (P = 0.013), and more PSOC tumors had LOH than PSPC tumors, 91% versus 65% (P = 0.042). P53 overexpression was detected in 80% of PSPC tumors. CONCLUSIONS: LOH occurs less frequently in PSPC compared to PSOC. Chromosomal regions with high frequencies of LOH common to PSPC and PSOC, such as 12p, 17p, 17q, and 18q, may harbor tumor suppressor genes important in the carcinogenesis of both malignancies and likely include p53.

Aged↗

The wisdom of hormone-replacement therapy in survivors of ovarian and endometrial cancer.

This article reviews the relationship between estrogen replacement therapy (ERT) and hormone replacement therapy (HRT) in the development of endometrial, ovarian, and breast cancers. The wisdom of HRT in survivors of ovarian and endometrial cancers is reviewed by critically analyzing recent data. Because of methodological limitations in the reported studies, there are no definite data to support the safety of ERT and HRT in survivors of ovarian or endometrial cancer.

Endometrial Neoplasms↗

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↗

Screening for gynecologic malignancies: A continuing responsibility.

Screening for cervical cancer with the Papanicolaou cervical smear has resulted in a decline in incidence and mortality from cervical cancer. Targeting the unscreened population is the next challenge to reduce the incidence of this disease further. Currently, there are no available screening modalities for endometrial or ovarian cancer. Breakthroughs in molecular genetics may result in screening tests for ovarian cancer.

Biomarkers, Tumor↗

Lymphedema: patient and provider education: current status and future trends.

BACKGROUND: The majority of patients schedules for breast surgery or radiation therapy for breast carcinoma do not receive basic information about the risk of lymphedema or its treatment. METHODS: A review of the literature documenting patient and provider education on the risk, prevention and treatment of lymphedema was undertaken. RESULTS: Formal education about lymphedema is not a part of the training of most medical and allied health professionals. Thus, patients do not receive information about the risk, prevention, or treatment of lymphedema. CONCLUSIONS: Educational strategies for patients and providers need to be developed and implemented.

Allied Health Personnel↗

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↗

Conservative management of uterine rhabdomyosarcoma.

BACKGROUND: Rhabdomyosarcomas are rare, malignant tumors derived from primitive myogenic precursors and are the most common soft tissue neoplasms in children and adolescents. We used primary chemotherapy and subsequent removal of the residual polypoid mass to treat an adolescent female with uterine rhabdomyosarcoma. CASE: A 15-year-old white adolescent who presented with a polypoid uterine rhabdomyosarcoma was treated with vincristine, etopside, and ifosfamide, after which the residual polypoid mass was removed. CONCLUSION: Treating adolescent females with a polypoid uterine rhabdomyosarcoma with primary chemotherapy followed by removal of the residual mass preserves reproductive function and should be considered.

Adolescent↗

All-trans retinoic acid and interferon-alpha-2a in patients with metastatic or recurrent carcinoma of the uterine cervix: clinical and pharmacokinetic studies. New York Gynecologic Oncology Group.

BACKGROUND: Recent clinical trials with a combination of interferon (IFN alpha) and 13 cis-retinoic acid resulted in high response rates among women with locally advanced and metastatic carcinoma of the uterine cervix. The authors sought to amplify these observations by employing the isomer of 13 cis-retinoic acid, all-trans retinoic acid (tRA), in combination with IFN alpha. METHODS: Sequential clinical trials were initiated by the New York Gynecologic Oncology Group to test the combination of tRA and IFN alpha in women with metastatic or recurrent carcinoma of the cervix who had failed primary therapy. IFN alpha was administered at 6 MU subcutaneously 3 times per week. In the first trial, tRA was administered at 50 mg/m2 orally 3 times per day on a daily schedule (daily regimen), whereas in the second trial, tRA was administered at the same dose 3 times per day, but only on Days 1-3 each week (intermittent schedule). Clinical outcomes included response to therapy and survival. Plasma pharmacokinetic studies of tRA were performed in both trials to assess the effects of different schedules on plasma levels of the drug. RESULTS: Fourteen women with metastatic or recurrent squamous cell carcinoma of the cervix were enrolled in the daily trial and 12 women in the intermittent trial. There was no clinical activity for either regimen, and both studies were terminated according to an early stopping rule. Because tRA has been reported to induce its own metabolism, plasma levels of tRA were measured on Days 1, 8, and 28. The change in the area under the time versus tRA concentration curve (AUC) was significantly different between the two groups. The average AUC on Day 8 was 14% of that observed on Day 1 for the daily treatment group; in contrast, it was 107% on Day 1 in the intermittent treatment group. In 6 of 8 patients studied in the daily trial, the AUC decreased at least 60% by either Week 2 or Week 4. In contrast, in the intermittent trial, only 3 of 9 patients experienced >60% decrease in plasma levels of the drug at either Day 8 or Day 28. CONCLUSIONS: The combination of tRA + IFN alpha was inactive in patients with advanced carcinoma of the cervix when employed at these doses on either the daily or intermittent schedule. The failure of activity of this regimen did not result from induction of metabolism of tRA, suggesting that intrinsic mechanisms of resistance to tRA at the cellular level may be of greater importance.

Adult↗

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↗

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↗

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↗