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Survival impact of cytoreduction to microscopic disease for advanced stage cancer of the uterine corpus: a retrospective cohort study

Alagkiozidis, Ioannis; Grossman, Allison; Tang, Nancy Z; Weedon, Jeremy; Mize, Benjamin; Salame, Ghadir; Lee, Yi-Chun; Abulafia, Ovadia
OBJECTIVE: To assess the impact of cytoreduction to no gross residual disease (R0) on overall survival (OS) in patients with stage III-IV uterine carcinosarcoma (CS), papillary serous/clear cell (UPSC/CC) and endometrioid carcinoma (EC). METHODS: We retrospectively identified 168 patients who underwent primary surgery for advanced uterine cancer between 1984 and 2009 in two teaching hospitals in Brooklyn, New York. Histology, stage, grade, residual disease (RD), adjuvant therapy, age, race and OS were collected. OS was calculated using the Kaplan-Meier method. Predictive factors were compared using the log-rank test and Cox regression analysis. RESULTS: Our cohort included 54 patients with CS (stage III, n = 32; stage IV, n = 22), 54 patients with UPSC/CC (stage III, n = 20; stage IV, n = 34) and 60 patients with EC (stage III, n = 45; stage IV, n = 15). R0 was achieved in 64% of patients with CS, in 53% of patients with UPSC/CC and in 68% of patients with EC. There was no interaction between histologic subtype and feasibility of complete cytoreduction (p = 0.39). R0 was associated with a median OS of 25 months (95% CI [18, 33]) versus 13 months (95% CI [8, 18]) in patients with gross RD (p = 0.03). This effect was uniform among histologic subtypes. On multivariate analysis, predictors of increased mortality were gross residual disease (HR = 2.0, 95% CI [1.1, 3.7], p = 0.01), stage IV (HR = 1.8, 95% CI [1.1, 3.1], p = 0.02) and age (HR = 1.04 per year of age, 95% CI [1.02, 1.07], p = 0.002). CONCLUSION: Cytoreductive surgery to R0 is associated with improved OS in advanced uterine cancer. This effect is uniform among histologies. There is no interaction between histologic subtype and feasibility of complete cytoreduction.
PMID: 25576762
ISSN: 1743-9159
CID: 1924092

Ex vivo Efficacy of Anti-Cancer Drug PNC-27 in the Treatment of Patient-Derived Epithelial Ovarian Cancer

Sarafraz-Yazdi, Ehsan; Gorelick, Constantine; Wagreich, Allison R; Salame, Ghadir; Angert, Mallorie; Gartman, Charles H; Gupta, Vinita; Bowne, Wilbur B; Lee, Yi-Chun; Abulafia, Ovadia; Pincus, Matthew R; Michl, Josef
OBJECTIVE: Despite an 80% response rate to chemotherapy, epithelial ovarian cancer has the highest case fatality rate of all gynecologic malignancies. Several studies have shown the efficiency of anticancer peptides PNC-27 and PNC-28 in killing a variety of cancer cells selectively in vitro and in vivo. The purpose of this study was to evaluate the efficacy of PNC-27 against human primary epithelial ovarian cancer. METHODS: We established primary cultures of freshly isolated epithelial ovarian cancer cells from patients with newly diagnosed ovarian cystadenocarcinomas. Two cell lines were obtained, one from mucinous cystadenocarcinoma, and the other from high-grade papillary serous carcinoma. The cancerous properties of these cells were characterized in vitro morphologically, by their growth requirements and serum independence. Treatment effects with PNC-27 were followed qualitatively by light microscopy, and quantitatively by measuring inhibition of cell growth using the MTT cell proliferation assay and direct cytotoxicity by measuring lactate dehydrogenase (LDH). RESULTS: PNC-27 inhibits in a dose-dependent manner the growth of and is cytotoxic to human primary cancer cells that had been freshly isolated from two ovarian epithelial cancers. The results further show that the control peptide PNC-29 has no effect on the primary cancer cells. Our results also show that PNC-27 is cytotoxic to cells from long-established and chemotherapy-resistant human ovarian cancer cell lines. CONCLUSION: These findings show, for the first time, the efficacy of PNC-27 on freshly isolated, primary human cancer cells. Our results indicate the potential of PNC-27 peptide as an efficient alternative treatment of previously untreated ovarian cancer as well as for ovarian cancers that have become resistant to present chemotherapies.
PMID: 26663795
ISSN: 1550-8080
CID: 1924062

Glassy cell carcinoma of the cervix: a systematic review and meta-analysis

Guitarte, Camilla; Alagkiozidis, Ioannis; Mize, Benjamin; Stevens, Erin; Salame, Ghadir; Lee, Yi-Chun
OBJECTIVE: The purpose of this study is to summarize the data on the incidence, clinical behavior and overall survival of patients with glassy cell cervical carcinoma (GCCC). METHODS: Twenty-four case series and fifteen case reports identified by searching PubMed database qualified for inclusion in this study. The published cases were combined with data from a retrospective chart review of patients with GCCC in two major teaching hospitals in Brooklyn, NY. RESULTS: A total of 292 cases were collected through our literature and chart review. Median age at diagnosis was 45 years old (range 12-87 years of age). GCCC incidence ranges from 0.2 to 9.3% of all cervical cancers and 2 to 30.2% of cervical adenocarcinomas. The stage distribution is similar to squamous cell carcinoma with 79% of the patients being diagnosed with Stage I or II disease. Most common sites of recurrence for Stage I patients are the vagina and pelvis. In Stage II patients locoregional and distant metastases are equally common. Recurrence rate was higher among patients treated only with surgery (32.7%), as compared to patients treated with surgery followed by radiation (11%) or patients treated with radiation only (10%). Median overall survival (OS) was 25 months (95% CI 8.4-41.6). Overall 5-year survival for all stages is lower when compared to all cervical cancers (54.8% vs 75%). There was no interaction between race and OS (p=0.66). CONCLUSION: GCCC is a rare histologic type of cervical cancer that presents at a younger age, is associated with high risk for distant failure and carries worse prognosis as compared to the squamous cell type. Radiation therapy is associated with decreased risk of recurrence.
PMID: 24503463
ISSN: 1095-6859
CID: 1924102

External validation of a nomogram for predicting survival of women with uterine cancer in a cohort of African American patients

Alagkiozidis, Ioannis; Wilson, Kirstie; Ruffner, Nicole; Weedon, Jeremy; Serur, Eli; Economos, Katherine; Abulafia, Ovadia; Lee, Yi-Chun; Salame, Ghadir
OBJECTIVE: This study aimed to externally validate a nomogram for predicting overall survival of women with uterine cancer in an African American population. METHODS: After the institutional review board approval, data from the uterine cancer database from 2 major teaching hospitals in Brooklyn, NY, were analyzed. The predicted survival for each patient was calculated with the use of the nonogram; the data were clustered in deciles and compared with the observed survival data. RESULTS: High incidence of aggressive histologic types (22% carcinosarcoma, 16% serous/clear cell), poorly differentiated (53% grade 3), and advanced stage (38% stage III or IV) tumors was found in our study population. The median follow-up for survivors was 52 months (range, 1-274 months). The observed and predicted 3-year overall survival probabilities were significantly different (62.5% vs 72.6%, P < 0.001). Similarly, the observed 5-year overall survival probability was significantly lower than the predicted by the nomogram (55.5% vs 63.4%, P < 0.001). The discrepancy between predicted and observed survival was more pronounced in the midrisk groups. CONCLUSIONS: The nomogram is not an adequate tool to predict survival in the African American population with cancer of the uterine corpus. Race seems to be a significant, independent factor that affects survival and should be included in predictive models.
PMID: 24362715
ISSN: 1525-1438
CID: 1890802

Port-site recurrence in a patient undergoing robotic hysterectomy and lymph node dissection for endometrioid adenocarcinoma of the uterus

Alagkiozidis, Ioannis; Zhining, Nancy T; Berulava, Giorgi; Abulafia, Ovadia; Salame, Ghadir
*We present a case of port-site recurrence of endometrioid adenocarcinoma after robotic hysterectomy and staging.*Port-site recurrence is commonly an indicator of multifocal disease with poor prognosis.*Surgical techniques that decrease the risk of this complication should be implemented.
PMCID:3862220
PMID: 24371704
ISSN: 2211-338x
CID: 1924112

Invasive recurrence of serous borderline ovarian tumor as multifocal lymphadenopathy 25 years after initial diagnosis

Alagkiozidis, Ioannis; Dorcelus, Sandy; Somma, Jonathan; Chun, Lee Yi; Salame, Ghadir
We present the case with the latest reported recurrence of low malignant potential ovarian tumor. Borderline ovarian tumors have the potential for delayed recurrence that is not always salvageable surgically. Optimization of surveillance strategies and lifelong follow up is required for these patients.
PMCID:3860968
PMID: 24371646
ISSN: 2211-338x
CID: 1924132

Medical management of recurrent endometrioma with long-term norethindrone acetate

Muneyyirci-Delale, Ozgul; Anopa, Jenny; Charles, Cassandra; Mathur, Deepali; Parris, Rudolph; Cutler, Jed B; Salame, Ghadir; Abulafia, Ovadia
PURPOSE: Evaluate the efficacy of norethindrone acetate in the resolution of symptoms and regression of recurrent endometrioma. PATIENTS AND METHODS: Retrospective chart review at SUNY Downstate Medical Center of patients with a history of surgical excision of endometrioma (with histological confirmation) and recurrent endometrioma (demonstrated by strict sonographic criterion of endometrioma) who were willing to undergo follow-up. Patients were prescribed norethindrone acetate to be taken daily with follow-up sonograms until cysts regressed. Statistical analysis included Student's t-test and a simple linear regression model to assess cyst regression over time during treatment. RESULTS: Degree of pain was significantly lower on treatment when compared to baseline (P < 0.00001). Cyst size was significantly smaller in as little as 3 months (P < 0.0001). Average rate of regression with continuous treatment was 0.025 +/- 0.015 cm/day. Total mean +/- standard deviation regression time is 10.28 +/- 8.25 months. CONCLUSION: Norethindrone acetate was effective in eradicating symptoms and producing complete regression of recurrent endometriomas. It should be considered for patients who are likely to adhere to a prolonged treatment regimen and comply with recommendations for surveillance with serial sonograms.
PMCID:3325007
PMID: 22505834
ISSN: 1179-1411
CID: 1924122

FIGO staging for carcinosarcoma: can the revised staging system predict overall survival?

Pradhan, Tana S; Stevens, Erin E; Ablavsky, Michael; Salame, Ghadir; Lee, Yi-Chun; Abulafia, Ovadia
OBJECTIVES: The purpose of this study is to detect differences in overall survival between the 1988 FIGO staging and current staging of uterine carcinosarcomas to determine if revised 2009 staging accurately predicts actual patient survival. METHODS: From 1988 until 2010, patients with uterine carcinosarcoma were retrospectively identified from tumor registry records. Patients were grouped in both broad stages (1-4) and all FIGO substages in order to detect differences. Time-dependent receiver operating characteristic curves (ROC) were generated to predict death before the end of the second year post-diagnosis for both the new and revised system. Kaplan Meier estimated median survival time was utilized to compare actual patient survival. RESULTS: Of 112 patients with carcinosarcoma, 37 patients (33%) had FIGO Stage I disease, 15 patients (13.4%) had Stage II disease, 36 patients (32%) were diagnosed as Stage III, and 24 patients (21.4%) had Stage IV disease. 106 of 112 (94.6%) patients underwent lymphadenectomy (pelvic +/- para-aortic). Four patients (3.6%) were downstaged when utilizing broad staging criteria: 2 patients were downstaged from Stage II to I, and 2 patients were downstaged from Stage III to Stage I and II respectively. When looking at substage, the area under the ROC was 0.67 for the former staging system, and 0.65 for the revised staging. Kaplan-Meier estimated median survival time post-diagnosis was 610 days (95% CI [478,930]). CONCLUSION: Based upon our reclassification of 112 patients with uterine carcinosarcoma, the revised FIGO staging system does not predict survival more accurately than former staging. Carcinosarcoma has an overall poor prognosis and better indicators of survival are needed.
PMID: 21889193
ISSN: 1095-6859
CID: 1924152

Large extraluminal leiomyoma of the rectum in a patient presenting with decreasing stool caliber [Letter]

Salame, Ghadir; Sherer, David M; Zinn, Harry L; Abulafia, Ovadia
PMID: 21968499
ISSN: 1550-9613
CID: 1924142

Sonographic Findings of Medullary Thyroid Carcinoma Leading to Diagnosis of Multiple Endocrine Neoplasia Type 2a during Pregnancy

Sherer, David M; Dalloul, Mudar; Salame, Ghadir; Shah, Tana; Serur, Eli; Zinn, Harry L; Abulafia, Ovadia
Multiple endocrine neoplasia (MEN) type 2a (Sipple's syndrome) is characterized by medullary thyroid carcinoma and pheochromocytoma, and in a smaller percentage of cases, multiglandular parathyroid hyperplasia. This autosomal-dominant syndrome is due to a mutation in the rearranged during transfection (RET) proto-oncogene located on chromosome 10cen-10q11.2 and rarely complicates pregnancy. We present an unusual case in a patient with an enlarged thyroid with sonographic findings characteristic of thyroid cancer, which led to diagnosis and subsequent management of RET proto-oncogene-positive MEN type 2a complicating pregnancy.
PMCID:3653543
PMID: 23705087
ISSN: 2157-6998
CID: 1890832