24 research outputs found
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Novel biologic therapies for the treatment of endometrial cancer
Over the past 20 years, options for patients with recurrent endometrial cancer have included radiation, chemotherapy, and hormonal therapy. None of these options have been shown to greatly impact mortality. We are currently investigating the role of molecular therapeutics for the treatment of this disease. By better understanding molecular pathways that are disregulated, we hope to identify rational biologic targets.
PTEN, a tumor suppressor gene, has been shown to play several roles in tumor suppression, including cell cycle arrest and promotion of apoptosis. The finding of PTEN mutations in 40–50% of endometrial cancers suggests this pathway is important in the pathogenesis of this disease. Loss of PTEN leads to constitutive activation of AKT, which in turn leads to upregulation of the mammalian target of rapamycin (mTOR). Because PTEN‐deficient cancer cells may have upregulated activity of the mTOR, these cells may be sensitive to mTOR inhibition. Our preliminary findings have demonstrated phosphorylated mTOR expression in over 70% of preliminary endometrial cancers and over 50% of recurrent endometrial cancers. In addition, expression of mTOR is present in all endometrial cancer cell lines studies. RAD001 is a novel macrolide, which is being developed as an antiproliferative drug with applications as an immunosuppressor and anticancer agent. In a phase II study, we are currently evaluating RAD001 for the treatment of recurrent endometrioid endometrial cancer.
The epidermal growth factor receptor (EGFR) is overexpressed in the two most common histologic subtypes of endometrial cancer: uterine papillary serous carcinoma (UPSC) and endometrioid endometrial cancer. Overexpression of this receptor has been associated with advanced stage disease and a poor prognosis. Because of this, we hypothesize that targeting this receptor may help stabilize disease in those patients with recurrent disease. We are in the process of initiating a phase II trial evaluating Erbitux (anti‐EGFR antibody) for the treatment of recurrent endometrial cancer.
Finally, we have previously reported that imatinib targeted kinases are overexpressed in endometrial carcinomas, specifically UPSC. In a phase I/II study, we are evaluating the combination of Gleevec and paclitaxel for the treatment of advanced and recurrent UPSC.
We feel that these studies may provide important information that will help improve the survival in the patients with recurrent endometrial cancer. In addition to clinical endpoints, we will be evaluating specific biologic endpoints that may help us to pre‐select patients for specific therapies and identify which agents may work in combination with other cytotoxic or biologic therapies
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Prevalence of high risk non-vaccine type HPV among U.S. women who received Cervarix or Gardasil: NHANES 2009-2014
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Advances in the management of advanced and recurrent uterine papillary serous carcinoma
Uterine papillary serous carcinoma (UPSC) is an aggressive subtype of endometrial cancer that accounts for 5–10% of all cases. Over 50% of the patients with UPSC present with advanced stage disease(1). Among patients with noninvasive uterine disease, 40% have advanced stage UPSC(1); therefore, complete surgical staging is crucial to determine prognosis and treatment(2). Optimal tumor debulking (<1cm) is associated with a better prognosis and improved overall survival(3). After initial surgical staging, patients with high stage UPSC have an improved overall survival if treated with chemotherapy (platinum‐based or paclitaxel‐based therapy)(1). Even with chemotherapy, the disease free interval is approximately 1 year(4–6). The role of radiation in these patients is unclear. Up to 30% of recurrences occur outside of the abdomen and pelvis (unpublished data). While the response rate to chemotherapy in the recurrent setting is up to 80%, the duration of response is approximately 7 months (4–6). Because the disease free interval in the adjuvant setting and the duration of response in patients with recurrent disease is limited, better strategies are needed to treat patients with this disease. We have recently evaluated Her‐2/neu overexpression and amplification in a series of patients with UPSC. Her‐2/neu overexpression was independently associated with a poor prognosis, however the rate of specific gene amplification was only 3%(7). We have found that imatinib‐targeted kinases are overexpressed in UPSC(8). We currently are evaluating imatinib (Gleevec, Novartis) and paclitaxel for the treatment of UPSC in patients with advanced or recurrent disease
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The Diagnosis of Abdomino-Pelvic Tuberculosis by Laparoscopically Assisted Peritoneal Biopsies
Lymphatic ascites following pelvic and paraaortic lymphadenectomy procedures for gynecologic malignancies
Lymphatic ascites is an unusual complication in patients with cancer. In the gynecologic oncology patient population, the most common etiology is operative lymph node dissection. The purpose of this study was to explore the incidence, presenting symptoms, methods of diagnosis and treatment modalities utilized for lymphatic ascites in patients undergoing lymph node dissection for gynecologic cancers.
This observational study retrospectively reviewed the charts of patients who underwent lymphadenectomy as part of the surgical management for a gynecologic cancer. Patients that developed postoperative lymphatic ascites between January 2000 and December 2010 were included for analysis. Data extracted from the medical records included tumor pathology, number of harvested lymph nodes, postoperative course, method of diagnosis and treatment.
From a total of 300 surgical staging procedures, 12 patients with lymphatic ascites were identified (4%). The most common reported symptom was leakage of clear fluid per vagina (7, 58%), followed by abdominal distension (4, 33%). The median interval from surgery to development of symptoms was 12.5days (range 0–22days). 5 patients had complete resolution of symptoms with dietary modifications alone while 7 patients required paracentesis. The median time from surgery to resolution of symptoms was 44days (range 9–99).
Lymphatic ascites is an under recognized and infrequently reported postoperative complication. Although it usually resolves spontaneously or with conservative management without sequelae, this condition can significantly prolong postoperative recovery and cause patient discomfort. To our knowledge this is the largest group of patients undergoing gynecologic surgical staging procedures to be reviewed for the occurrence of lymphatic ascites.
► We have reviewed 300 gynecologic staging procedures that include lymphadenectomy and identified 12 patients who developed lymphatic ascites (4%). ► The most commonly reported presenting symptoms of lymphatic ascites were leakage of clear vaginal fluid and abdominal distension. ► The median interval from surgery to development of symptoms was 12.5days
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Clinicopathologic features of early adenocarcinoma of the cervix initially managed with cervical conization
To evaluate the clinicopathologic features of microinvasive adenocarcinoma of the cervix in order to guide the management of patients with this disease.
A retrospective review was conducted of patients diagnosed with early invasive, ≤
5 mm stromal invasion, adenocarcinoma of the cervix by a cervical conization between 1992 and 1999 at our institution. Information was abstracted on tumor histopathologic type, grade, and depth of invasion as well as presence or absence of disease at the margins of conization, lymphovascular spread, and the presence of disease in subsequent pathology specimens including the parametrium and pelvic lymph nodes (PLNs).
Thirty-three patients were identified. The mean age of the patients in the study population was 41.6 years (range, 29–53 years). Fifteen women were age 35 years or younger. Six patients had invasion ≤
1 mm, 9 patients had invasion >
1 mm and ≤
2 mm, 6 patients had invasion >
2 mm and ≤
3 mm, 6 patients had invasion >
3 mm and ≤
4 mm, and 6 patients had invasion >
4 mm and ≤
5 mm.
Three patients were treated with a conization only, 4 patients were treated with a simple hysterectomy, 25 patients were treated with a radical hysterectomy (RH) and PLN dissection (PLND), and 1 patient was treated with a radical trachelectomy and PLND. Ten patients had positive conization margins for invasive cancer, 3 patients had margins positive for adenocarcinoma in situ, 14 patients had negative margins, and in 6 patients the margin status could not be evaluated. Of the 10 patients with positive margins, 5 of 10 (50%) had residual disease in the subsequent surgical specimen. Three patients who underwent definitive management with conization alone originally had positive margins, underwent a second repeat conization, and are included in this group. Of the 16 patients with negative margins, no patient had residual disease in a subsequent surgical specimen. Of the 25 patients who underwent a RH and PLND, none had parametrial involvement and none had PLN involvement. All patients remained without evidence of disease at median follow-up of 30 months.
Historically, the standard management of early invasive adenocarcinoma of the cervix has been controversial, and some clinicians continue to favor radical treatments. Based on the absence of parametrial spread and PLN involvement in early lesions, physicians and patients should consider treatment with conization with negative margins (when future fertility is desired) or simple hysterectomy. Prospective studies are required to document the safety of this approach
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