Katharine M. Esselen

Genomic aberrations in cervical adenocarcinomas in Hong Kong Chinese women.

Although the rates of cervical squamous cell carcinoma have been declining, the rates of cervical adenocarcinoma are increasing in some countries. Outcomes for advanced cervical adenocarcinoma remain poor. Precision mapping of genetic alterations in cervical adenocarcinoma may enable better selection of therapies and deliver improved outcomes when combined with new sequencing diagnostics. We present whole‐exome sequencing results from 15 cervical adenocarcinomas and paired normal samples from Hong Kong Chinese women. These data revealed a heterogeneous mutation spectrum and identified several frequently altered genes including FAT1, ARID1A, ERBB2 and PIK3CA. Exome sequencing identified human papillomavirus (HPV) sequences in 13 tumors in which the HPV genome might have integrated into and hence disrupted the functions of certain exons, raising the possibility that HPV integration can alter pathways other than p53 and pRb. Together, these provisionary data suggest the potential for individualized therapies for cervical adenocarcinoma based on genomic information.

Patterns of recurrence in advanced epithelial ovarian, fallopian tube and peritoneal cancers treated with intraperitoneal chemotherapy

OBJECTIVES To examine the distribution and outcomes of recurrent disease in patients with ovarian, fallopian tube and peritoneal cancers after optimal cytoreduction and adjuvant intraperitoneal (IP) chemotherapy. METHODS All patients diagnosed with ovarian, fallopian tube, or peritoneal cancer between 2004 and 2009 who underwent optimal cytoreductive surgery and received adjuvant intravenous (IV) and IP chemotherapy with paclitaxel and a platinum-based agent were eligible. Age, performance status, tumor origin, stage, and grade were recorded. First recurrences were identified using CA125 values, radiographic studies, operative notes, and pathology reports. Sites of recurrence were classified as intraperitoneal (IP), extraperitoneal (EP) or distant. Kaplan-Meier estimates and Cox multivariate regression models were used to assess the associations between recurrent disease distribution and progression-free survival (PFS) and overall survival (OS). RESULTS One hundred forty-three patients met the criteria for inclusion. The majority were Stage III (86%) and serous histology (77%). Eighty-four (58.7%) received IV/IP paclitaxel/cisplatin per GOG-172 and 59 (41.3%) received IV/IP paclitaxel/carboplatin. Seventy-two percent completed 6 cycles. Ninety (62.9%) patients manifested a recurrence. One-hundred twelve sites of recurrence were identified with 70 (62.5%) IP and 42 (37.5%) EP and distant sites. Nineteen (21%) recurred in more than one site, i.e. both IP and EP locations. Site of recurrence did not impact OS, however, patients who recurred in multiples sites had significantly worse OS (p<0.001). CONCLUSION Approximately 40% of patients treated with IP chemotherapy have a first recurrence outside the peritoneal cavity. Though site of recurrence did not affect OS those with multi-focal recurrence demonstrate worse survival.

Defining prognostic variables in recurrent endometrioid endometrial cancer: a 15-year single-institution review.

Objective: This study aimed to examine the pattern of recurrence in patients with endometrioid endometrial cancer and to identify clinically important prognostic factors in the recurrent population. Methods: With institutional review board approval, a retrospective review identified 1061 patients who underwent primary surgery and treatment of endometrioid endometrial cancer at our institution from 1994 to 2007. Of this cohort, 77 (7.2%) patients developed a recurrence. Clinical factors were recorded, and Spearman correlation coefficients and &khgr;2 test were used to determine associations between groups. Kaplan-Meier survival estimates and Cox proportional-hazards model were used to determine how prognostic variables affected survival after recurrence (RS) and overall survival (OS). Results: Of 77 patients, site of recurrence was not available in 5 patients. The distribution of recurrence in the remaining 72 patients was as follows: isolated vaginal 18% (13/72), nonvaginal pelvic 12% (9/72), distant 31% (22/72), abdominal 24% (17/72), and nodal 15% (11/72). There was an overrepresentation of advanced stage (P < 0.001) and high-grade (P < 0.003) at presentation in the recurrent group. Median OS was 3.4 years and median RS was 1.3 years. Low-grade tumors, early stage, and those with less than 50% myometrial invasion were associated with a significant OS and RS advantage. Age-adjusted isolated vaginal recurrence presented with a 1.2-year RS survival advantage (P < 0.03). An age-adjusted Cox proportional hazard ratio model incorporating significant prognostic variables demonstrated that the only independent variable associated with worse OS and RS was increased histologic grade with a hazard ratio of 2.31 (95% confidence interval, 1.25-3.97) for RS and 2.44 (95% confidence interval, 1.41-4.62) for OS. Conclusions: Those patients with high-grade histology at the time of initial diagnosis manifest a decreased OS and RS, suggesting that the intrinsic biology of the tumor has the greatest prognostic importance.

Health Care Disparities in Hysterectomy for Gynecologic Cancers: Data From the 2012 National Inpatient Sample.

OBJECTIVE: To examine hysterectomies in the United States performed for gynecologic malignancies and identify factors associated with the use of minimally invasive techniques. METHODS: This is a cross-sectional analysis of the 2012 National Inpatient Sample, the largest national all-payer database of hospital discharges. International Classification of Diseases, 9th Revision, Clinical Modification codes for any type of hysterectomy performed for gynecologic malignancy were used to abstract pertinent observations. Weighted multivariable logistic regression models were used to examine the associations between demographic and clinical factors and mode of hysterectomy by cancer diagnosis. RESULTS: In 2012, there were an estimated 46,450 hysterectomies for gynecologic malignancy in the United States. Of these, 28,285 (61%) were performed for uterine, 4,275 (9%) for cervical, 12,370 (27%) for ovarian cancer, and 1,520 (3%) for other gynecologic malignancies. Minimally invasive hysterectomy was used in 50% of uterine, 43% of cervical, and 8.5% of ovarian cancer cases. Black women had decreased odds of undergoing minimally invasive hysterectomy for uterine (adjusted odds ratio [OR] 0.50, 95% confidence interval [CI] 0.40–0.0.63, P<.001) and cervical (adjusted OR 0.56, 95% CI 0.33–0.96, P=.03) cancers. Those without insurance or with Medicaid had decreased odds of undergoing minimally invasive hysterectomy (P<.001) for uterine cancer. As compared with the Northeast, patients in the South (adjusted OR 0.72, 95% CI 0.53–0.98, P=.04) were less likely to undergo minimally invasive hysterectomy for uterine cancer, whereas those in the West more likely (adjusted OR 1.48, 95% CI 1.10–1.99, P=.009). CONCLUSION: Minimally invasive hysterectomy for gynecologic malignancies remained underused in 2012; there were striking racial disparities associated with use of minimally invasive hysterectomy for uterine and cervical cancers. LEVEL OF EVIDENCE: III

Endosalpingiosis as it relates to tubal, ovarian and serous neoplastic tissues: An immunohistochemical study of tubal and Müllerian antigens

OBJECTIVE The origins and clinical significance of endosalpingiosis (ES), ectopic tubal epithelium, are not well understood. These investigations aim to characterize ES as it relates to normal fallopian tube, ovarian surface and serous neoplasms. METHODS A retrospective review of pathology reports from all prophylactic gynecologic surgeries from 2000 to 2010 was performed to assess the frequency of ES. Twenty-one archival specimens of ES, 6 normal fallopian tubes, 9 normal ovaries, 21 serous neoplasms and a commercially available ovarian tissue microarray were subjected to immunohistochemistry (IHC) with 11 tubal and Müllerian antigens. IHC staining was evaluated with a quantitative scoring system and scores were analyzed using MINITAB statistical software. RESULTS ES was noted in 3.5% of pathologic specimens from 464 prophylactic surgeries. The majority of antigens showed no significant differences (p > 0.05) in median IHC scores between ES and normal fallopian tube epithelium (nFTE), while they were significantly different (p < 0.05) from the ovarian surface epithelium (OSE). Median IHC scores were unchanged in ES tissues regardless of the location of ES or the presence of a concurrent serous neoplasm. Three antigens emerged as contemporary tubal and ES biomarkers: phospho-Smad2, BCL2 and FOXJ1. All 3 biomarkers were expressed in ES, nFTE and serous neoplasms, but not in OSE or other tumor types. CONCLUSION This study provides immunophenotypic evidence that ES is more similar to the nFTE than OSE. Further, ES biomarker expression closely resembles serous neoplasms strengthening the growing body of evidence that all Müllerian serous carcinomas arise from tubal-like epithelium.

Does plastic surgical consultation improve the outcome of patients undergoing radical vulvectomy for squamous cell carcinoma of the vulva

OBJECTIVES To analyze margin status and prognostic factors for complications in patients undergoing vulvectomy for invasive squamous cell cancer (iSCC) with and without plastic-assisted closure. METHODS Demographic and clinical data were collected on 94 patients with iSCC who underwent vulvectomy between 2004 and 2013. All pathology slides were re-reviewed by two gynecologic pathologists. Data were analyzed using XLSTAT-Pro v2014.2.02. RESULTS Of 88 eligible patients, 15 (17%) had plastic-assisted vulvar closure and 73 (83%) did not. There were significantly more patients in the plastics group with recurrent disease (53% v 10%) and history radiation therapy prior to surgery (40% versus 5%). Plastic-assisted closure was associated with larger tumors (3.73 cm versus 2.03 cm, p<0.01) and a higher frequency of adequate margins (53% versus 29%, p=0.06). For tumors≥3.0 cm, plastic-assisted closure was significantly associated with adequate margins (44% versus 6%, p=0.03). Prior radiation use was associated with plastic-assisted closure, larger tumors, older age, and recurrent disease. Complications occurred in 36 patients (41%) and significantly more occurred in those with plastic-assisted closure (67% versus 36%, p=0.04). On multivariate analysis including age, tumor size, recurrent disease, plastic-assisted closure, and history of radiation, only history of radiation therapy was a significant predictor of complications (OR=17, 95%CI 2.05-141.35; p=0.01). CONCLUSIONS Plastic-assisted vulvectomy closure was more often utilized in cases involving past radiation therapy and larger tumors. Plastic-assisted closure significantly increased the frequency of adequate margins in tumors≥3 cm and did not impact complications.

Cost-effectiveness of cervical cancer prevention.

Cost-effectiveness analyses are an important tool for the evaluation and modification of many health care services. Given the variety of screening tests and treatments available for cervical cancer screening and prevention, the costs associated with these options and with their alternatives, and the differences in resources and settings in which these tests are applied worldwide, cost-effectiveness analyses evaluation can be very useful to help determine best practices.

Patterns of recurrence in patients treated with bevacizumab in the primary treatment of advanced epithelial ovarian cancer

Objective The purpose of this study was to compare the distribution of the first site of recurrence in patients with epithelial ovarian cancer (EOC) who received first-line treatment with bevacizumab compared with patients who did not receive bevacizumab. Methods From the Cancer Registry database at our institutions, we identified a group of patients with recurrent EOC who underwent treatment from January 1, 2005, to December 31, 2010. Each patient record was evaluated to classify the site of first recurrence. Correlation between categorical variables was assessed with χ2 test. Results Two hundred ninety-two patients with advanced EOC (stage III or IV) who originally responded to chemotherapy and had a recurrence were identified. Of these, 37 (12.5%) had received postoperative chemotherapy bevacizumab, and 255 (87.5%) did not. Compared with those not treated with bevacizumab, there was a lower incidence of liver recurrence (0% vs 9%; P = 0.05) and a higher rate of lung and/or pleural recurrence (22% vs 5%; P = 0.001) and recurrence at distant sites (22% vs 9%; P = 0.03) in patients who received bevacizumab. There was no difference in the incidence of ascites at the time of recurrence between these groups. Conclusions Patients who received bevacizumab as part of primary treatment for EOC had a higher rate of lung and/or pleural recurrence and a lower rate of liver recurrence. There was no difference in the rate of ascites at the time of recurrence.

Solitary Fibrous Tumor of the Uterus Presenting With Lung Metastases: A Case Report.

We describe the case of an 81-yr-old woman who presented with bilateral pulmonary nodules in the setting of a large uterine mass, concerning for a gynecologic malignancy such as leiomyosarcoma. However, fine-needle aspiration of a lung nodule revealed a spindle cell neoplasm consistent with solitary fibrous tumor (SFT), a rare mesenchymal neoplasm characterized by a patternless architecture of spindle cells and branching ectatic vessels. Total abdominal hysterectomy demonstrated a primary SFT of the uterus. Both the lung lesion and uterine mass were positive for STAT6, a sensitive and specific biomarker for SFT. SFT infrequently metastasizes and only rarely occurs in the uterus. These tumors are considered to have uncertain malignant potential, and the diagnosis of “malignant” SFT requires the presence of >4 mitoses per 10 high-power fields. The uterine SFT we report did not meet this criterion for malignancy, emphasizing that this entity can behave aggressively even without increased mitoses or atypical histology. To our knowledge, this is the first reported case of a uterine SFT with metastasis to the lung. We discuss the differential diagnosis for the finding of multiple pulmonary spindle cell lesions in the setting of a uterine mass.

Participation in global health delivery: Survey results from the Society of Gynecologic Oncology

Highlights • Gynecologic oncologists face multiple barriers in participating in global health.• Several barriers may be addressed at the institutional level.• Most global health experiences involved direct patient care, while only a small proportion involved research.• Gynecologic oncologists receive little structured training in global health.