Real-Time Single-Walled Carbon Nanotube-Based Fluorescence Imaging Improves Survival after Debulking Surgery in an Ovarian Cancer Model.

Improved cytoreductive surgery for advanced stage ovarian cancer (OC) represents a critical challenge in the treatment of the disease. Optimal debulking reaching no evidence of macroscopic disease is the primary surgical end point with a demonstrated survival advantage. Targeted molecule-based fluorescence imaging offers complete tumor resection down to the microscopic scale. We used a custom-built reflectance/fluorescence imaging system with an orthotopic OC mouse model to both quantify tumor detectability and evaluate the effect of fluorescence image-guided surgery on post-operative survival. The contrast agent is an intraperitoneal injectable nanomolecular probe, composed of single-walled carbon nanotubes, coupled to an M13 bacteriophage carrying a modified peptide binding to the SPARC protein, an extracellular protein overexpressed in OC. The imaging system is capable of detecting a second near-infrared window fluorescence (1000-1700 nm) and can display real-time video imagery to guide intraoperative tumor debulking. We observed high microscopic tumor detection with a pixel-limited resolution of 200 µm. Moreover, in a survival-surgery orthotopic OC mouse model, we demonstrated an increased survival benefit for animals treated with fluorescence image-guided surgical resection compared to standard surgery.

Ovarian cancer: markers of response.

OBJECTIVES: Despite improved knowledge regarding the etiology of ovarian cancer, as well as application of aggressive surgery and chemotherapy, there has been only a modest change in the mortality statistics over the last 30 years. Given these results and the evolution of targeted therapies, there is an increasing need for prognostic and predictive factors to stratify patients for individualized care. Many laboratories have also investigated the specific individual biomarkers correlating them with clinicopathologic characteristics. Unfortunately, the vast majorities of these biomarkers have not proved clinically valuable. In this article, we review published genomic signatures including data generated in our laboratory for their relevance. METHODS: Multiple published expression profiling articles were selected for review and discussion. Genomic studies were separated from those with dichotomized survival data and unsupervised analysis to identify discreet subsets of tumors and studies that generated activated pathways. RESULTS: The identification of prognostic and predictive individual biomarkers has been common. Few of these have been validated. Genomic profiles have been obtained that distinguish short- from long-term survivors. The relevance of these studies to the large number of patients within the extremes remains unclear. Unsupervised clustering studies of ovarian cancers have identified potential subsets of tumors that reflect different clinical behavior. These studies will require large numbers of independent samples for validation. Another approach has been to identify genes that correlate with patient survival as a continuous variable. These genes are then placed into biologic context using pathway analysis. These pathways provide potential therapeutic targets, and those patients whose tumors express these targets may be most effectively treated by using inhibitors specific for the pathway. CONCLUSIONS: There is a major need for prognostic and predictive biomarkers for ovarian cancer. With the development of new genomic technologies, there is an opportunity to identify gene expression signatures that can be used to stratify patients according to their ultimate survival and response to chemotherapy. Large independent sets and robust statistical techniques will be required to fully exploit this approach.

Successful use of magnetic resonance-guided focused ultrasound surgery to relieve symptoms in a patient with symptomatic focal adenomyosis.

OBJECTIVE: To report a successful treatment of symptomatic adenomyosis using magnetic resonance-guided focused ultrasound surgery (MRgFUS). DESIGN: Case study. SETTING: General hospital. PATIENT(S): A 47-year-old premenopausal woman with focal symptomatic adenomyosis. INTERVENTION(S): MRgFUS. MAIN OUTCOME MEASURE(S): Score on the Uterine Fibroids Symptoms Quality of Life (UFS-QOL) questionnaire and the degree of menstrual pain. RESULT(S): Uterine Fibroids Symptoms reduced from 53 to 28 and the degree of menstrual pain reduced from 10 to 5. CONCLUSION(S): For adenomyosis patients who wish to preserve their uterus, MRgFUS may be a promising alternative to hysterectomy. Additional studies of the safety and efficacy of MRgFUS in this indication should be conducted.

Patient selection guidelines in MR-guided focused ultrasound surgery of uterine fibroids: a pictorial guide to relevant findings in screening pelvic MRI.

Uterine leiomyomas (fibroids), the most common benign tumor in women of childbearing age, can cause symptoms including dysmenorrhea, menorrhagia, urinary symptoms, pain and infertility. Hysterectomy is a common approach to treating uterine fibroids, and less invasive surgical approaches such as myomectomy and uterine artery embolization also have been shown to alleviate symptoms. Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is the only totally non-invasive surgical approved method for treating uterine fibroids. In clinical trials, MRgFUS resulted in significant relief of uterine fibroid symptoms. The safe and effective use of MRgFUS is affected by fibroid type and location, position relative to adjacent anatomical structures and the presence of co-existent pelvic disease. Additionally, successful outcomes with MRgFUS have been correlated with the volume of fibroids ablated during the procedure. Thus, selection of patients in whom sufficient fibroid volumes can be treated safely using the MRgFUS system is critical for successful outcomes. The MR images in this pictorial essay provide examples of uterine fibroids for which MRgFUS should be considered and is designed to facilitate the selection of patients for whom MRgFUS is most likely to provide sustained symptom relief.

Studying changes in the incidence, diagnosis and management of GTD: the South Korean model.

OBJECTIVE: To evaluate the changing epidemiologic picture and clinical characteristics of gestational trophoblastic disease (GTD) in South Korea over the past 5 decades. STUDY DESIGN: Patient data were collected from 37 hospitals nationwide, the Korean Research Institute of Trophoblastic Disease registry and CHA University Comprehensive Gynecologic Cancer Center from the years of 1970s through the year 2002. Demographic data, pretreatment evaluation, treatment modality, chemotherapeutic regimen and their results according to the clinical International Federation of Gynecology and Obstetrics classification and World Health Organization prognostic score were analyzed. Management of high-risk gestational trophoblastic tumor (GTT) was reviewed in depth. RESULTS: The nationwide incidence of hydatidiform mole and GTT dropped from 40.0 per 1,000 deliveries and 5.0 per 1,000 deliveries, respectively, in the 1970s to 2.0 per 1,000 deliveries and 0.5 per 1,000 deliveries, respectively, in the 1990s. The rate of decline was slower in 2000-2002. Significant changes were also noted in age distribution, interval between the preceding pregnancy and disease, gravidity and parity, and distribution of low- and high-risk groups of GTT. CONCLUSION: The dramatic improvement in GTD over the past 5 decades in South Korea can be attributed to the following factors: refinement in terminology and classification, advances in pretreatment evaluation, development of effective chemotherapeutic agents, application of multimodal treatment and novel chemoagents for high-risk GTT.