Susie Lau

In vitro metformin anti-neoplastic activity in epithelial ovarian cancer

OBJECTIVE Metformin, a commonly used drug in the treatment of type II diabetes, may reduce cancer risk and improve cancer prognosis. We evaluated its effect on epithelial ovarian cancer cell lines. METHODS The OVCAR-3 and OVCAR-4 cell lines were exposed to metformin with and without cisplatin. Cytotoxicity assays were performed in triplicates using the Alamar colorimetric assay. Levels of total and phosphorylated AMPK, p70S6K and S6K were evaluated by Western blotting following exposure to metformin. RESULTS Metformin induces dose- and time-dependent growth inhibition of OVCAR-3 and OVCAR-4 cell lines. Metformin potentiated the effect of cisplatin in vitro. Metformin growth inhibition was partly abolished by the AMPK inhibitor, compound C. Western blotting demonstrated that metformin at cytotoxic concentrations, induced AMPK phosphorylation and decreased p70S6K and S6K phosphorylation, suggesting the mechanism for its anti-proliferative action. CONCLUSION Metformin significantly inhibits the growth of ovarian cancer cell lines and potentiates cisplatin. Further pre-clinical studies are being conducted to determine the applicability of metformin in the treatment of ovarian cancer.

Outcomes and cost comparisons after introducing a robotics program for endometrial cancer surgery.

OBJECTIVE: To evaluate the effect of introducing a robotic program on cost and patient outcome. METHODS: This was a prospective evaluation of clinical outcome and cost after introducing a robotics program for the treatment of endometrial cancer and a retrospective comparison to the entire historical cohort. RESULTS: Consecutive patients with endometrial cancer who underwent robotic surgery (n=143) were compared with all consecutive patients who underwent surgery (n=160) before robotics. The rate of minimally invasive surgery increased from 17% performed by laparoscopy to 98% performed by robotics in 2 years. The patient characteristics were comparable in both eras, except for a higher body mass index in the robotics era (median 29.8 compared with 27.6; P<.005). Patients undergoing robotics had longer operating times (233 compared with 206 minutes), but fewer adverse events (13% compared with 42%; P<.001), lower estimated median blood loss (50 compared with 200 mL; P<.001), and shorter median hospital stay (1 compared with 5 days; P<.001). The overall hospital costs were significantly lower for robotics compared with the historical group (Can

The Meaning‐Making intervention (MMi) appears to increase meaning in life in advanced ovarian cancer: a randomized controlled pilot study

7,644 compared with Can

Comparing indocyanine green, technetium, and blue dye for sentinel lymph node mapping in endometrial cancer.

10,368 [Canadian dollars]; P<.001) even when acquisition and maintenance cost were included (Can

Accuracy of sentinel lymph node detection following intra-operative cervical injection for endometrial cancer: A prospective study

8,370 compared with Can

Phase II study of oral ridaforolimus in women with recurrent or metastatic endometrial cancer

10,368; P=.001). Within 2 years after surgery, the short-term recurrence rate appeared lower in the robotics group compared with the historic cohort (11 recurrences compared with 19 recurrences; P<.001). CONCLUSION: Introduction of robotics for endometrial cancer surgery increased the proportion of patients benefitting from minimally invasive surgery, improved short-term outcomes, and resulted in lower hospital costs. LEVEL OF EVIDENCE: II

Impact of robotics on the outcome of elderly patients with endometrial cancer

Objective: This pilot study aimed to provide supportive evidence for the acceptability and usefulness of the Meaning‐Making intervention (MMi) in patients newly diagnosed with Stage III or IV ovarian cancer, and to provide estimates of parameters needed to design a full‐scale study.

Relationship between body mass index and robotic surgery outcomes of women diagnosed with endometrial cancer.

BACKGROUND AND AIMS With the debate over extent of lymphadenectomy in endometrial cancer, sentinel lymph node (SLN) mapping may provide a focused approach to evaluate the most relevant lymph nodes (LN) while minimizing the complications. We evaluated SLN mapping using filtered technetium(99), indocyanine green (ICG), and blue dye. METHODS Prospective evaluation of 100 patients who underwent SLN mapping by using submucosal and deep stromal cervical injections of technetium(99), ICG, and blue dye as part of the staging for endometrial cancer. RESULTS 286 SLNs were mapped (2.9 per patient) in 92% of patients. The bilateral detection rate was 76%. ICG had a significantly higher SLN detection rate than blue dye in both overall (87% vs 71%, respectively; p=0.005) and bilateral (65% vs 43%, respectively; p=0.002) detection, but similar SLN detection rates compared to technetium(99) in both overall (87% vs 88%, respectively; p=0.83) and bilateral (65% vs 71%, respectively; p=0.36) detection. In eight cases, the SLN was in the para-aortic area and in 14 cases in the pre-sacral, hypogastric vein, or parametrial area. In nine cases, the SLN was positive for metastasis, and in seven cases the SLN was the only positive node. One SLN was falsely negative. No complications or anaphylactic reactions occurred. CONCLUSION Intra-operative SLN mapping using cervical injection is feasible in patients with endometrial cancer and yields adequate detection rates. It allows mapping of SLNs in areas (pre-sacral, hypogastric vein, parametrial) not routinely sampled. Given the poorer performance of blue dye, surgeons may omit its use if a combination of ICG and technetium(99) is used.

Outcome and quality of life in a prospective cohort of the first 100 robotic surgeries for endometrial cancer, with focus on elderly patients.

OBJECTIVE The objective of this study is to evaluate the detection rate and diagnostic accuracy of sentinel lymph node (SLN) mapping using intra-operative cervical injection of filtered 99mTc-sulfur colloid (99mTc-SC) and patent blue in patients with endometrial cancer. METHODS Prospective evaluation of the first 100 endometrial cancer patients undergoing SLN mapping using cervical injection of patent blue combined with filtered 99mTc-SC in the operating room was done. Patients underwent robotic-assisted lymphatic mapping with frozen section, hysterectomy, BSO, and completion bilateral lymphadenectomy (including para-aortic nodes in grade 2 and 3 tumors). RESULTS At least one SLN was detected in 92% of patients; in 66 of these (72%) bilateral SLN were detected, and in 15 cases the SLN was in the para-aortic area. Eleven percent of all patients had lymph node metastases, and 4 of which had pre-operative grade 1 tumor. The SLN was the only positive node in 44% of the cases with positive nodes. Sensitivity was 89% with 1 false negative result, yielding a negative predictive value of 99% (95% CI 93-100). Specificity was 100% (95% CI 94-100), and positive predictive value was 100% (95% CI 60-100). No complications or anaphylactic reactions were noted. CONCLUSIONS Intra-operative SLN biopsy, using cervical injection of patent blue and filtered 99mTc-SC in endometrial cancer patients is feasible and yields adequate detection rates.

Initial Evaluation and Referral Guidelines for Management of Pelvic/Ovarian Masses

OBJECTIVE The phosphatidylinositol-3 kinase/serine-threonine kinase PI3K/AKT pathway is postulated to be central to cancer cell development. Activation of this pathway is believed to promote angiogenesis, protein translation and cell cycle progression. A large percentage of endometrial carcinomas have demonstrated mutations within this regulation pathway which result in constitutional activation. The downstream effector protein mammalian target of rapamycin (mTOR) acts as a critical checkpoint in cancer cell cycling and is a logical target for drug development. The efficacy and tolerability of the oral mTOR inhibitor ridaforolimus were evaluated in this study. METHODS This phase II study evaluated the single agent tolerability and activity of oral ridaforolimus administered at a dose of 40mg for 5 consecutive days followed by a 2day break, in women with recurrent or metastatic endometrial carcinoma who had received no chemotherapy in the metastatic setting. RESULTS 31 of 34 patients were evaluable. Three partial responses (8.8%) were observed with response duration ranging between 7.9 and 26.5months. An additional 18 patients showed disease stabilization (52.9%) for a median duration of 6.6months. Response rates were not affected by previous chemotherapy exposure. No correlation was found between response and mutation status. CONCLUSION Oral ridaforolimus was reasonably tolerated and demonstrated modest activity in women with recurrent or metastatic endometrial cancers. Potential synergy between mTOR inhibition, angiogenesis and hormonal pathways warrants ongoing evaluation.