Emily Berry

FGFR3-TACC3: A novel gene fusion in cervical cancer.

Cervical cancer epitomizes the success of cancer prevention through the human papillomavirus (HPV) vaccine, but significant challenges remain in the treatment of advanced disease. We report the first three cases of cervical carcinoma harboring an FGFR3–TACC3 fusion, which serves as a novel therapeutic target. The fusion, identified by comprehensive genomic profiling, activates the FGFR pathway that has been implicated in HPV-driven carcinogenesis. One of the patients whose tumor contained the FGFR3–TACC3 fusion was treated with an investigational FGFR tyrosine kinase inhibitor. Concomitant molecular alterations involving the PI3K/AKT/mTOR and RAF/MEK pathways were also identified and suggest other treatment strategies that deserve investigation. This case series highlights the role of comprehensive genomic profiling in the identification of new therapeutic targets and in targeted therapy selection for patients with cervical cancer.

Induction of apoptosis in endometrial cancer cells by psammaplysene A involves FOXO1

OBJECTIVE Endometrial cancer is the most common type of gynecologic cancer in the United States. In this study, we propose that a marine sponge compound, psammaplysene A (PsA) induces apoptosis in endometrial cancer cells through forced nuclear expression of FOXO1. METHODS Ishikawa and ECC1 cells were treated with varying doses of PsA. FOXO1 protein localization was observed using immunofluorescent staining of cells. The effects of PsA on cell viability and proliferation were assessed using a cell viability assay and a BrdU incorporation assay respectively. Cell cycle analysis was performed using flow cytometry. To assess the role of FOXO1 in PsA-induced apoptosis, FOXO1 was silenced in ECC1 cells using siRNA technique, and overexpressed in Ishikawa cells using an adenovirus containing FOXO1 cDNAs. Western blots were used to measure levels of FOXO1 and cleaved PARP proteins. RESULTS Treatment of both ECC1 and Ishikawa cells with PsA caused an increase in nuclear FOXO1 protein, a dramatic decrease in cell viability of approximately 5-fold (p<0.05) and minimal effect on proliferation. Furthermore, treatment of cells with PsA doubled the percentage of cells in the G2/M phase (p<0.05). PsA induced apoptosis in endometrial cancer cells. When FOXO1 was silenced in ECC1 cells and treated with PsA, the incidence of apoptosis decreased. In addition, overexpression of FOXO1 with PsA treatment increased apoptosis. CONCLUSIONS Increasing nuclear FOXO1 function is important for the induction of apoptosis of endometrial cancer cells by PsA.

Sonohysterography and endometrial cancer: incidence and functional viability of disseminated malignant cells

OBJECTIVE The purpose of this study was to evaluate sonohysterography in patients with endometrial cancer and to determine whether (1) transtubal fluid spill occurs during routine sonohysterography, (2) a critical infusion volume for spill exists, or (3) disseminated cancer cells demonstrate viability. STUDY DESIGN At laparotomy, sonohysterography was performed on 16 patients with endometrial adenocarcinoma. Volumes at which tubal spill occurred were recorded. Collected specimens were processed and incubated. After evaluation for viable cells, cytologic analysis was undertaken. RESULTS The median volume that was required for adequate sonohysterography was 8.5 mL. Five patients (31%) had transtubal spill. With an additional saline solution flush, the median total volume for a spill was 20.5 mL. Two patients (12.5%) had viable benign cells that were cultured after routine sonohysterography. One patient (6%) had nonviable carcinoma cells that were identified. CONCLUSION Transtubal spill occurs during sonohysterography. No critical spill volume was identified. A highly diagnostic tool when abnormal bleeding is evaluated, sonohysterography has a low probability of cancer cell dissemination.

A Comparison of Survival and Recurrence Outcomes in Patients With Endometrial Cancer Undergoing Robotic Versus Open Surgery

OBJECTIVE To compare recurrence and survival outcomes in women who underwent either robotic or open surgical procedures to treat endometrial cancer. DESIGN A retrospective chart review (Canadian Tack Force classification II-2). SETTING A single academic institution. PATIENTS A total of 936 patients who underwent surgical staging for endometrial cancer between 2001 and 2013. INTERVENTION Through retrospective chart review, data were collected on patient characteristics, surgical procedures, intraoperative and postoperative complications, histopathology, adjuvant therapies, and recurrence and survival outcomes. Estimated 3-year progression-free survival and 5-year overall survival were calculated using Kaplan-Meier curves. MAIN RESULTS Of the 936 patients who underwent endometrial cancer surgery, 350 had robotic-assisted surgery and 586 had laparotomy. Both groups were comparable in terms of age, race, body mass index, and comorbid conditions. The laparotomy group had significantly more patients with grade 2-3 tumors, nonendometrioid histology, and stage III-IV disease. In a multivariate analysis, operative type was not an independent prognostic factor for intraoperative complications, but robotic surgery was associated with decreased postoperative complications and readmission rate. Median duration of follow-up was 30 months in the robotic cohort and 42 months in the laparotomy cohort. Estimated 3-year progression-free survival was 90.87% for the robotic group and 78.30% for the laparotomy group, and estimated 5-year overall survival was 89.14%for the robotic group and 79.47% for the laparotomy group. In a multivariate analysis, including stage, grade, histology, operative type, and adjuvant therapy, operative type was not an independent prognostic factor for recurrence or overall survival. CONCLUSION Compared with laparotomy, robotic staging for endometrial cancer is associated with less postoperative morbidity without compromising short-term recurrence rates or survival outcomes.

Volunteering in Honduras: Results and Reflections

According to the GLOBOCAN 2012 data released by the International Agency for Research on Cancer, an estimated 14.1 million new cancer cases and 8.2 million cancer deaths occurred worldwide in 2012. This is an immense increase compared with 2008 statistics, which reported 12.7 and 7.6 million new cases and deaths, respectively. Lowand low-middle–income countries accounted for more than half of the new cancer cases and nearly two thirds of all cancerrelated deaths. The social and economic disparities in cancer prevention and treatment present a disproportionate burden in these low-resource settings. Honduras is a low-middle–income country with a total population of 8.3 million. Cancer accounts for 13% of deaths each year. The most common cancers reported are prostate, gastric, cervix, liver, and breast. The mortality rates from cervix and gastric cancers are among the highest globally, at 18.5 and 8.8%, respectively. There are 24 surgical, eight gynecologic, 13 medical, and four radiation oncologists in Honduras. Hospital General San Felipe (HGSF) is the only public cancer hospital in Honduras that treats underserved patients. Currently, there is only one surgical oncology training program in Honduras. During the 4-year curriculum, residents are taught to provide surgical care for men and women with a wide spectrum of malignancies. Efforts to improve the education and training of residents in surgery and oncology in countries with limited specialists have been growing in the last decade. Medical volunteerism in such countries has become an area of interest for medical students, residents, fellows, and attending physicians from outside of the affected countries, and there are a number of models for providing this assistance. Barriers to successful exchanges between volunteers and in-country physicians include time constraints of the volunteers and infrastructure deficits in low-resource settings that prohibit optimal learning environments. Increasingly, a combination of short-term, hands-on teaching sessions coupled with ongoing Internet-based instruction by volunteers at a distance has emerged as a successful model for supporting incountry physicians to provide increasingly sophisticated medical and surgical care within the limits of available resources. For example, a successful program of surgical training to perform radical hysterectomies in patients with cervical cancer has been implemented in Kenya through collaboration with the Society of Gynaecologic Oncology of Canada. The 2-week intensive program, which is staffed by one expert Canadian surgeon, included seven video didactics, a preand post-test, and seven live surgical sessions with oral and written feedback after each patient case. Short-term follow-up revealed four successful radical hysterectomies by the Kenyan surgeons after the Canadian trainer had left. Similarly, the Central America Gynecologic Oncology Education Program, an initiative that is focused on the education and training of obstetrics and gynecology residents in the prevention and treatment of gynecologic cancers, is a collaboration between the American College of Obstetrics and Gynecology and six Central American countries and includes in-country training trips with US gynecologic oncologists with ongoing distance learning and support. Another option for training physicians from low-resource settings is for these individuals to travel to high-resource settings for training. However, this approach has drawbacks. A recent report suggests that the numbers of physicians emigrating from Sub-Saharan Africa to the US is increasing and will negatively affect low-resource countries, where there is a great need for health care providers. Training of physicians in their respective countries offers the advantage of hands-on training, given that direct patient contact is not allowed during an observership in the United States. In addition, the context of care and the resources available for treatment are different in settings such as Honduras compared with the United States. Despite increasing numbers of medical missions to assist underserved countries, there is still a lack of formalized educational curricula and supervised training in these countries. In this article, we describe the Health Volunteers Overseas (HVO) Oncology Training Program in Honduras, which focuses on providing education, surgical training, and research mentorship to surgical oncology residents, nurses, and other health care providers in Tegucigalpa, Honduras.

The “hook effect” causing a negative pregnancy test in a patient with an advanced molar pregnancy

Highlights • At high hCG levels in molar pregnancies, a “hook effect” can cause an artificially negative value.• Delay in diagnosis of a molar pregnancy due to the “hook effect” can lead to severe complications.• Suspicion of a molar pregnancy should be communicated so a diluted sample is used to quantify hCG.

Cancer survivorship care in the rural community: A mobile model.

38 Background: As survival rates continue to improve, many forms of cancer are now regarded as chronic diseases requiring long-term follow-up. This survivorship phase of care represents a distinct opportunity to improve the health and quality of life for cancer survivors, addressing the lingering medical and psychosocial effects of illness, recurrent or new cancers, and promoting health behavior changes. Evidence-based cancer survivorship programs are typically limited in scope and only found in large cancer centers because they are costly and poorly reimbursed. As a result, UT Southwestern Moncrief Cancer Institute (UTSW-MCI) mobilized its clinic to provide essential survivorship services to the estimated 15,000 underserved cancer survivors in geographically remote areas of North Texas. METHODS UTSW-MCI provides survivorship care to Medicaid-enrolled and uninsured patients within a nine county service area using a custom-built mobile health unit. Staffed with an experienced team of nurses, social workers, dietitians, exercise specialists and physician assistant, services on the mobile clinic include: cancer screening and surveillance; medical management of long-term side effects of treatment; treatment summary and care plans; dietary evaluations and healthy lifestyle education; psychosocial evaluations, care coordination and navigation to financial assistance; and assessments for balance, immobility, range of motion, and safe physical activity. In-house providers with the ambulatory clinic are also able to see patients on the mobile unit using telemedicine. These services include genetic counseling, physician assistant evaluations, and psychological counseling. RESULTS After six months, mobile clinic enrollments represent more than 10% (N = 28) of the survivorship program patient population and nearly 15% (N = 130) of completed encounters, including 28 RN assessments, 26 Social Work evaluations, 21 Dietitian assessments, 53 Exercise sessions, and 3 PA consultations. CONCLUSIONS This innovative survivorship care model addresses barriers that impede access to care to improve both the health of medically underserved cancer survivors and the experience of care while reducing the cost of care without compromising quality.