Endometrial cancer recurrence after the use of a uterine manipulator during laparoscopic surgery.

Objective: Minimally invasive surgery (MIS) is the standard approach for the staging and treatment of early-stage endometrial cancer (EC) and often includes use of a uterine manipulator. Uterine perforation is a known risk in this setting, and the impact of perforation and tumor spillage on cancer recurrence is largely unknown. The aim of this study was to assess the association between uterine perforation and/or tumor spillage at the time of MIS for low-grade, early-stage EC on disease recurrence.

Qualitative results from a randomized pilot study of eHealth Mindful Movement and Breathing to improve gynecologic cancer surgery outcomes.

Purpose: Improved management of pain and co-morbid symptoms (sleep disturbances, psychological distress) among women undergoing surgery for suspected gynecologic malignancies may reach a population vulnerable to chronic pain.

Participants: Women undergoing surgery for a suspected gynecologic malignancy.

Method: We conducted a pilot randomized controlled trial of eHealth Mindful Movement and Breathing (eMMB) compared to an empathic attention control (AC).

HIPEC after neoadjuvant chemotherapy is associated with acceptable toxicity and favorable quality of life in newly diagnosed advanced ovarian cancer patients.

Objective: To evaluate toxicity, quality of life and PFS in patients with advanced ovarian cancer who underwent neoadjuvant chemotherapy (NAC) followed by CRS and HIPEC with carboplatin.

Methods: Patients with stage IIIC or IVA epithelial ovarian cancer, who were not candidates for primary CRS, were enrolled in this phase two trial. Patients received 3-6 cycles of NAC with an IV carboplatin doublet followed by CRS with HIPEC (carboplatin 800 mg/m for 90 min).

Beyond Sedlis-A novel histology-specific nomogram for predicting cervical cancer recurrence risk: An NRG/GOG ancillary analysis.

Purpose: The Sedlis criteria define risk factors for recurrence warranting post-hysterectomy radiation for early-stage cervical cancer; however, these factors were defined for squamous cell carcinoma (SCC) at an estimated recurrence risk of ≥30%. Our study evaluates and compares risk factors for recurrence for cervical SCC compared with adenocarcinoma (AC) and develops histology-specific nomograms to estimate risk of recurrence and guide adjuvant treatment.

Methods: We performed an ancillary analysis of GOG 49, 92, and 141, and included stage I patients who were surgically managed and received no neoadjuvant/adjuvant therapy.

Preoperative Circulating Lymphocyte and Monocyte Counts Correlate with Patient Outcomes in Type I and Type II Endometrial Cancer.

Tumor-associated macrophages and tumor-infiltrating lymphocytes are associated with survival in solid malignancies. Given the physiological link to peripheral immune cell counts, we evaluated if peripheral immune cell counts were predictors of outcomes in endometrial cancer. A retrospective study was completed for endometrial cancer cases between 2000 and 2010.

Identification of orally-bioavailable antagonists of the TRPV4 ion-channel.

Antagonists of the TRPV4 receptor were identified using a focused screen, followed by a limited optimization program. The leading compounds obtained from this exercise, RN-1665 23 and RN-9893 26, showed moderate oral bioavailability when dosed to rats. The lead molecule, RN-9893 26, inhibited human, rat and murine variants of TRPV4, and showed excellent selectivity over related TRP receptors, such as TRPV1, TRPV3 and TRPM8.

Serum Calcium and Serum Albumin Are Biomarkers That Can Discriminate Malignant from Benign Pelvic Masses.

Background: Biomarkers that aid in the differential diagnosis of malignant pelvic masses from benign ones prior to surgery are needed in order to triage women with malignant masses to appropriate specialist care. Because high albumin-adjusted serum calcium predicted ovarian cancer among women without evidence of disease, we hypothesized that it might predict cancer among women with pelvic masses that were evident radiographically.

Methods: We studied a cohort of 514 women with pelvic masses who underwent resection at Wake Forest University Baptist Medical Center from July 2009 through June 2013.

Xanthogranulomatous Oophoritis Presenting as an Adnexal Mass and Bowel Obstruction. A Case Report.

Background: Xanthogranulomatous inflammation of the female genital tract is a rare entity. When the gynecological organs are affected, it is particularly unusual for xanthogranulomataus inflammation to involve only the ovary.

Case: A 45-year-old woman with an intrauterine device, long-term exposure to nicotine, and hyperlipidemia presented with an adnexal mass and bowel obstruction.

Type 2 Endometrial Cancer is Associated With a High Density of Tumor-Associated Macrophages in the Stromal Compartment.

Introduction: Tumor-associated macrophages (TAMs) play a pivotal role in orchestrating the microenvironment. The TAMs differentially polarize into M1 or M2 macrophages with distinct actions. The aim of our work is to characterize density, subtype, and location of TAMs in endometrial hyperplasia and cancer.

Surgical risk score predicts suboptimal debulking or a major perioperative complication in patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer.

Background: Patients who present with an advanced ovarian cancer are typically treated with primary debulking surgery (PDS) or neoadjuvant chemotherapy (NAC) followed by interval debulking surgery. The accurate pretreatment identification of patients best suited for PDS versus NAC is challenging. A paradigm for selecting one approach over the other could improve patient outcomes.

Phase II evaluation of phenoxodiol in combination with cisplatin or paclitaxel in women with platinum/taxane-refractory/resistant epithelial ovarian, fallopian tube, or primary peritoneal cancers.

Introduction: Chemoresistance is a major limitation in the treatment of ovarian cancer. Phenoxodiol is a novel biomodulator capable of reversing chemoresistance in vitro and in vivo. In this study, we determined the safety and efficacy of intravenous phenoxodiol in combination with cisplatin or paclitaxel in women with platinum/taxane-refractory/resistant ovarian cancers.

Large cell neuroendocrine carcinoma of the cervix: prognostic factors and survival advantage with platinum chemotherapy.

Objective: Large cell neuroendocrine carcinoma of the cervix (LCNEC) is a rare cervical neoplasm associated with poor survival. Our objective was to identify treatments associated with improved survival.

Methods: Relevant data were abstracted from an English literature MEDLINE search, SEER database, and a patient treated at our institution.

The discovery of an orally efficacious positive allosteric modulator of the calcium sensing receptor containing a dibenzylamine core.

The discovery of a series of novel and orally efficacious type II calcimimetics, developed from the lead compound 1, is described herein. Compound 22 suppressed plasma PTH levels relative to vehicle when dosed orally in a rat pharmacodynamic model.

Oxime derivatives related to AP18: Agonists and antagonists of the TRPA1 receptor.

AP18 1 was recently disclosed as an antagonist of the TRPA1 receptor by the research group of Patapoutian. However, no detailed structure-activity relationships around 1 have been disclosed. Thus, a small number of oximes related to AP18 were examined in order to characterize the determinants of TRPA1 activity.

Mining biologically-active molecules for inhibitors of fatty acid amide hydrolase (FAAH): identification of phenmedipham and amperozide as FAAH inhibitors.

The screening of known medicinal agents against new biological targets has been shown to be a valuable approach for revealing new pharmacology of marketed compounds. Recently, carbamate, urea and ketone inhibitors of fatty acid amide hydrolase (FAAH) have been described as promising treatments for pain, anxiety, depression and other CNS-related conditions. In order to find novel FAAH inhibitors, a focused screen of molecules containing potentially reactive moieties or having in vivo effects that are possibly relevant to the biology of FAAH was conducted.

Identification and characterization of novel TRPV4 modulators.

TRPV4, a close relative of the vanilloid receptor TRPV1, is activated by diverse modalities such as endogenous lipid ligands, hypotonicity, protein kinases and, possibly, mechanical inputs. While its multiple roles in vivo are being explored with KO mice and selective agonists, there is a dearth of selective antagonists available to examine TRPV4 function. Herein we detail the use of a focused library of commercial compounds in order to identify RN-1747 and RN-1734, a pair of structurally related small molecules endowed with TRPV4 agonist and antagonist properties, respectively.

Preparation of heteroaryloxetanes and heteroarylazetidines by use of a Minisci reaction.

Introduction of oxetan-3-yl and azetidin-3-yl groups into heteroaromatic bases was achieved by using a radical addition method (Minisci reaction). To demonstrate utility, the process was used to introduce an oxetane or azetidine into heteroaromatic systems that have found important uses in the drug discovery industry, such as the marketed EGFR inhibitor gefitinib, a quinolinecarbonitrile Src tyrosine kinase inhibitor, and the antimalarial hydroquinine.

Preparation of aryloxetanes and arylazetidines by use of an alkyl-aryl suzuki coupling.

The oxetan-3-yl and azetidin-3-yl substituents have previously been identified as privileged motifs within medicinal chemistry. An efficient approach to installing these two modules into aromatic systems, using a nickel-mediated alkyl-aryl Suzuki coupling, is presented.

Neoadjuvant chemotherapy lessens surgical morbidity in advanced ovarian cancer and leads to improved survival in stage IV disease.

Objectives: To compare the survival and peri-operative morbidities of patients with advanced epithelial ovarian cancer (EOC, stage IIIC and IV) who were treated with primary debulking surgery (PDS) followed by adjuvant platinum-based chemotherapy, or neoadjuvant chemotherapy followed by cytoreductive surgery (NAC).

Methods: 172 patients with advanced EOC diagnosed at YNHH (1998-2005) were retrospectively reviewed. 109 patients were treated with PDS and 63 patients were treated with NAC [37 received carboplatin/paclitaxel (CP), 26 received carboplatin/cyclophosphamide (CC)].

Atypical presentations of carboplatin hypersensitivity reactions: characterization and management in patients with gynecologic malignancies.

Objectives: Carboplatin skin testing (ST) can help identify patients with platinum hypersensitivity (PH), however, we have encountered patients who do not immediately test positive yet exhibit subtle or delayed allergy symptoms prior to PH. We describe the "atypical platinum reactions" (APH) of 14 patients and our experience with skin testing and desensitization.

Methods: Retrospective chart review was performed on carboplatin-treated patients.

Inflammatory bowel disease and the lung: is there a link between surgery and bronchiectasis?

Purpose: One-third of patients with inflammatory bowel disease (IBD) has extracolonic manifestations. Inflammatory bowel-associated pulmonary disease is one of the less commonly recognized and more recently described manifestations. Here, we report the experience of our patients with inflammatory bowel-associated bronchiectasis.

TLR-4 signaling promotes tumor growth and paclitaxel chemoresistance in ovarian cancer.

Evidence suggests that an inflammatory profile of cytokines and chemokines persisting at a particular site would lead to the development of a chronic disease. Recent studies implicate bacterial infection as one possible link between inflammation and carcinogenesis; however, the crucial molecular pathways involved remain unknown. We hypothesized that one possible upstream signaling pathway leading to inflammation in carcinogenesis may be mediated by Toll-like receptors (TLR).