Genetics and the Gynecologic Patient.

The field of hereditary cancer syndromes and genetic testing for patients and families is a rapidly evolving discipline, with an emphasis on cancer prevention. We review the literature regarding the most common genetic syndromes associated with gynecologic malignancies and discuss the management of these conditions. We also examine the logistic process surrounding cancer genetic testing and identify some perceived barriers.

Molecular Response to Neoadjuvant Chemotherapy in High-Grade Serous Ovarian Carcinoma.

While high-grade serous ovarian carcinoma (HGSOC) is the most common histologic subtype of ovarian cancer, significant tumor heterogeneity exists. In addition, chemotherapy induces changes in gene expression and alters the mutational profile. To evaluate the notion that patients with HGSOC could be better classified for optimal treatment based on gene expression, we compared genetic variants [by DNA next-generation sequencing (NGS) using a 50 gene Ion Torrent panel] and gene expression (using the NanoString PanCancer 770 gene Panel) in the tumor from 20 patients with HGSOC before and after neoadjuvant chemotherapy (NACT).

Characteristics of African American women at high-risk for ovarian cancer in the southeast: Results from a Gynecologic Cancer Risk Assessment Clinic.

Objectives: Describe patient characteristics in African American (AA) women seen for gynecologic cancer related genetic counseling at a large southeastern comprehensive cancer center.

Methods: We reviewed an IRB approved, prospective observational cohort of patients from a Gynecologic Cancer Risk Assessment Clinic. Data evaluated included personal cancer history, family history, frequency of genetic testing, frequency/type of genetic mutations, and frequency of surgical intervention.

Does a standardized preoperative algorithm of clinical data improve outcomes in patients with ovarian cancer? A quality improvement project.

Objective: To evaluate the potential impact of a standardized preoperative algorithm on outcomes of patients with suspected ovarian cancer.

Methods: From January 1 to December 31, 2013, patients with suspected ovarian cancer were triaged to primary debulking surgery or neoadjuvant chemotherapy/interval debulking surgery (NACT/IDS) based on a comprehensive review of preoperative clinical data as part of a quality improvement project. Demographics, surgical, and postoperative data were collected.

Incidence of port site hernias and/or dehiscence in robotic-assisted procedures in gynecologic oncology patients.

Objectives: The incidence of port site hernia and/or dehiscence using bladeless trocars is 0-1.2%. Robotic surgery uses additional port sites and increases manipulation of instruments, raising the concern for more complications.

Treatment of chemotherapy-induced anemia in ovarian cancer patients: does the use of erythropoiesis-stimulating agents worsen survival?

Objective: Considering the paucity of data relating erythropoiesis-stimulating agent (ESA) use to ovarian cancer survival, our objective was to evaluate the effect of ESA as used for the treatment of chemotherapy-induced anemia (CIA) on survival in ovarian cancer patients.

Materials And Methods: A multi-institution retrospective chart review was performed on ovarian cancer patients. Data collection included patient demographic, surgicopathologic, chemotherapy, ESA, and survival data.

Incidence of mechanical malfunction in low-profile subcutaneous implantable venous access devices in patients receiving chemotherapy for gynecologic malignancies.

Objective: The purpose of this study was to investigate the incidence of mechanical complications associated with low-profile subcutaneous implantable venous access devices in gynecologic oncology patients.

Methods: Gynecologic oncology patients with low-profile Port-a-Caths implanted between March 2005 and July 2006 were identified into a computerized database. Patient demographics, operative complications, number of chemotherapy cycles, duration of implantation, and mechanical complications were collected.

Conservative management of postoperative Fever in gynecologic patients undergoing major abdominal or vaginal operations.

Background: To develop a standardized protocol for management of postoperative fever in gynecology patients to decrease unnecessary diagnostic workups and empiric use of antibiotics.

Study Design: A prospective analysis of postoperative gynecology patients identified those who experienced fever (maximum temperature [T(max)] > 100.4 degrees F).

A phase I study of lapatinib in combination with carboplatin in women with platinum sensitive recurrent ovarian carcinoma.

Objectives: To determine the maximum tolerated dose (MTD), spectrum of toxicities, clinical activity, and pharmacokinetics of carboplatin given in combination with lapatinib in women with a first recurrence of platinum sensitive epithelial ovarian carcinoma.

Methods: Patients with measurable, platinum sensitive recurrent epithelial ovarian carcinoma were eligible. Cohorts of 3-6 patients were to receive up to 6 cycles of intravenous carboplatin AUC of 6 every 21 days in combination with escalating dosages of oral lapatinib (starting at a dose of 750 mg daily).

Lynch syndrome in women less than 50 years of age with endometrial cancer.

Objective: To estimate the frequency of mismatch repair deficiencies associated with hereditary nonpolyposis colorectal cancer, or Lynch syndrome, in women less than age 50 with endometrial cancer.

Methods: Consecutive patients less than age 50 diagnosed with endometrial adenocarcinoma were identified. Available pathologic specimens were freshly sliced, and protein expression for MLH1, MSH2, MSH6, and PMS2 was evaluated by immunohistochemistry.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its therapeutic potential in breast and gynecologic cancers.

Objective: The relationship between the apoptotic pathway and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising area of scientific interest for cancer researchers. TRAIL-receptor-activating agents have demonstrated favorable in vitro and in vivo activity for the treatment of several malignancies including breast and gynecologic cancers.

Methods: This article reviews the available peer-reviewed literature and our own institution's experience with specific TRAIL-receptor-activating agents.

Diagnostic loop electrosurgical excisional procedure for discrepancy: do preoperative factors predict presence of significant cervical intraepithelial neoplasia?

Objective: Although pathological discrepancy between Pap smear and biopsy is an accepted indication to perform a diagnostic loop electrosurgical excision procedure (LEEP), this procedure is not without complications. Our objective was to determine the incidence of cervical intraepithelial neoplasia (CIN) 2,3 and patient factors that increase the likelihood of detecting CIN 2,3.

Materials And Methods: We performed a retrospective chart review of patients who underwent a diagnostic LEEP for pathological discrepancy at a university-based colposcopy clinic.

Efficacy of anti-death receptor 5 (DR5) antibody (TRA-8) against primary human ovarian carcinoma using a novel ex vivo tissue slice model.

Objectives: The purpose of this study was to evaluate the cytotoxicity of a death receptor 5 (DR5) targeting monoclonal antibody (TRA-8) in primary ovarian cancer specimens utilizing a tissue slice technique that allows for assessment of anti-tumor activity in a three-dimensional ex vivo model.

Methods: Nineteen primary ovarian tumor specimens were obtained at the time of cytoreductive surgery and tumor slices were prepared with the Krumdieck tissue slicer. Tumor slices were incubated with TRA-8 for 24 h and a dose-response curve was established for each specimen using non-linear modeling, with IC50 values used as the parameter of TRA-8 sensitivity.

Autoclave sterilization of instruments used on women with cervical neoplasia is an effective method of eradicating residual human papillomavirus DNA: a polymerase chain reaction-based evaluation.

Objective: To determine whether autoclave sterilization eradicates human papillomavirus (HPV) DNA on specula and instruments used to treat women with cervical neoplasia.

Methods: Specula and instruments used in two referral colposcopy clinics were evaluated to determine the PGMY9/11 primer system's ability to amplify residual HPV DNA. Each speculum and instrument was sampled with a Dacron swab and stored in PreservCyt solution (Cytyc Corporation, Marlborough, MA) at 4 degrees C.

The honeymoon is over.

Background: The importance of a broad differential diagnosis is highlighted by a complex patient case.

Case: A young woman returned from her honeymoon complaining of activity-limiting pain. The evaluation revealed multiple constitutional symptoms, a breast mass, a large pelvic mass, pulmonary abnormalities, an external iliac venous thrombosis, and lytic bone lesions.

Bowel resection at the time of primary debulking for epithelial ovarian carcinoma: outcomes in patients treated with platinum and taxane-based chemotherapy.

Background: Our goal was to determine the morbidity, disease-free survival, and overall survival of patients with bowel resection at primary cytoreductive surgery for advanced epithelial ovarian carcinoma in the era of platinum and taxane chemotherapy.

Study Design: We performed a retrospective study of patients undergoing bowel resection at the time of primary cytoreduction for advanced epithelial ovarian carcinoma, who subsequently received platinum and taxane chemotherapy, from 1996 to 2001. Data collected included demographics, stage, histology, debulking status, surgical morbidity, recurrence, and survival.

Role of chemotherapy for patients with recurrent platinum-resistant advanced epithelial ovarian cancer: A cost-effectiveness analysis.

Background: Current chemotherapy in platinum-resistant ovarian cancer patients has demonstrated minimal to no improvements in survival. Despite the lack of benefit, significant resources are utilized with such therapies. Therefore, the objective in the current study was to assess the cost-effectiveness of salvage chemotherapy for patients with platinum-resistant epithelial ovarian cancer (EOC).

Efficacy and toxicity of the novel chemotherapeutic agent KW-2170 in recurrent epithelial ovarian cancer.

Objectives: KW-2170 is a novel DNA intercalating agent whose mechanism of action is similar to doxorubicin HCl, yet is associated with less cardiac toxicity. The objective of this study was to evaluate the activity and toxicity of this novel chemotherapeutic agent in patients with recurrent ovarian carcinoma.

Methods: A prospective phase II trial was performed in patients with persistent or recurrent epithelial ovarian or primary peritoneal carcinoma and measurable disease.

Traumatic diaphragmatic rupture: a rare cause of postoperative shortness of breath.

Background: Shortness of breath is a common symptom reported by patients after gynecologic procedures. Delayed traumatic diaphragmatic rupture is a rare cause of shortness of breath.

Case: This report describes the diagnosis and management of a patient with a delayed presentation of a ruptured right hemidiaphragm after a laparotomy for a pelvic mass.

Management strategies for stage IB2 cervical cancer: a cost-effectiveness analysis.

Objective: To assess the potential effectiveness and medical costs of three common strategies to manage Stage IB2 squamous cell carcinoma of the cervix (CXCA).

Methods: A decision analysis model compared three strategies to manage Stage IB2 CXCA: (1) radical hysterectomy with pelvic and para-aortic lymphadenectomy followed by tailored chemoradiation therapy for high-risk patients (RHYST); (2) primary chemoradiation therapy for all patients (CTRT); and (3) neoadjuvant chemotherapy followed by radical hysterectomy and tailored chemoradiation therapy for high-risk patients (NAC).

Results: RHYST was the least expensive strategy with a cost of 284 Million (M) per 10,000 women and a 5-year disease free survival (5-DFS) of 69%.

Retrospective analysis of weekly topotecan as salvage therapy in relapsed ovarian cancer.

Objective: To retrospectively investigate the safety and efficacy of weekly topotecan in heavily pretreated patients with ovarian cancer.

Methods: Data were collected by retrospective review of patient records. Eligible patients had received > or =2 prior regimens for ovarian cancer before treatment with weekly topotecan.

The impact of aborted radical hysterectomy in patients with cervical carcinoma.

Objective: To determine the impact of an aborted radical hysterectomy on morbidity and overall survival in patients undergoing surgical treatment for early stage cervical carcinoma.

Methods: Following IRB approval, a computerized database identified 304 women treated with radical surgery for early stage cervical carcinoma from 1994 to 2000 of which 23 (8%) had an aborted radical hysterectomy.

Results: Of the 23 patients, 17 patients had a IB(1) lesion, 4 patients had a IB(2) lesion, and 2 patients had a IIA lesion.

Complications of indwelling venous access devices in patients with gynecologic malignancies.

Objective: The purpose of this study was to evaluate the complication rates associated with indwelling venous access devices in patients with gynecologic malignancies.

Methods: Following IRB approval, a computerized database identified women that had indwelling access devices placed for chemotherapy from March 1999 to June 2001. A retrospective chart review identified 116 venous access devices that were placed in 104 patients.