Feasibility of intraoperative injection of radioactive tracer and blue dye for sentinel lymph node biopsy in vulvar cancer.

OBJECTIVE: The objective of this study was to examine the feasibility and success rate of intraoperative injection of radiotracer and blue dye performed by the surgeon without the use of preoperative lymphoscintigraphy for the detection of sentinel lymph nodes in clinically early stage vulvar cancer. METHODS: All patients with clinically early stage vulvar cancer who underwent attempted sentinel lymph node biopsy using intraoperative injection of Technetium-99 m (99mTc) tracer and blue dye performed by the surgeon after induction of anesthesia at single academic institution from 12/2009 to 5/2022 were identified. Demographic and clinicopathologic variables were collected. Data were compared using descriptive statistics. RESULTS: One hundred sixty-four patients (median age 66.4 years) underwent intraoperative injection of radioactive tracer and dye for sentinel lymph node biopsy. Most patients (n = 156, 95.1%) were white. Squamous cell carcinoma accounted for 138 cases (84.1%), melanoma for 10 (6.1%), extra-mammary invasive Paget's disease for 11 (6.7%), and other histologies for 5 (3%). A majority of cases were stage I disease on final pathology (n = 119, 72.6%). Most patients (n = 117, 71%) had tumors located within 2 cm of the midline and underwent planned bilateral groin assessment, while 47 (29%) had well lateralized lesions and underwent unilateral groin assessment. For the patients undergoing unilateral groin assessment, 44 of 47 (93.6%) had successful unilateral mapping. Of the patients who underwent bilateral groin assessment, 87 of 117 (74.4%) had successful bilateral mapping, and 26 of 117 (22.2%) had successful unilateral mapping. Of the 26 patients who underwent bilateral assessment but only had unilateral mapping, 19 had unilateral mapping to ipsilateral groin but failed contralateral mapping, six had midline lesions with successful mapping to one groin but failed mapping to the other groin, and one had unilateral mapping to the contralateral groin but not ipsilateral groin. The total successful sentinel lymph node mapping rate in this cohort was 86.5% (243/281 total sentinel lymph node attempts). CONCLUSION: In this cohort, the overall success rate of sentinel lymph node mapping and biopsy was 86.5%. The high rate of successful sentinel lymph node mapping supports the use of intraoperative radiotracer and blue dye injection by trained providers.

Unplanned postoperative intensive care unit admission for ovarian cancer cytoreduction is associated with significant decrease in overall survival.

OBJECTIVES: Previous studies have identified age, nutritional status, and hematocrit as risk factors for unplanned ICU admission in gynecologic oncology patients. We sought to identify additional perioperative factors that can be predictive of unplanned ICU admission and its impact on outcomes in women with ovarian cancer undergoing ovarian cancer cytoreductive procedures. METHODS: This was a case-control study of patients with unplanned ICU admission after primary surgery for ovarian cancer from January 2007 to December 2013. Controls were selected in a 2:1 ratio matching for primary surgeon and date of surgery. Clinical data was abstracted and compared between cases and controls using conditional logistic regression. RESULTS: The dataset consisted of 324 patients (108 ICU admissions, 216 controls). On multivariable analysis, failure to optimally cytoreduce (p = 0.001, OR 3.76) and higher EBL (p < 0.001, OR 1.20 per 100 cm3) remained significant predictors of unplanned ICU admission. On multivariable analysis of outcomes, ICU admission was independently associated with increased length of stay (12 days vs. 6 days, p < 0.001), increased number of postop complications (2 vs. 0, p < 0.001), and increased risk of readmission within 30 days (p = 0.041, OR 2.46). Even controlling for debulking status, ICU admission remained associated with a worse median OS (27.3 vs 57.9 months, p < 0.001). CONCLUSIONS: ICU admission for women undergoing cytoreductive surgery for ovarian cancer is associated with a significant decrease in OS and increase in number of postoperative complications. For this inherently high-risk population, this information is critical when counseling patients about peri-operative risks in primary cytoreductive surgery.

Cell-permeable, small-molecule activators of the insulin-degrading enzyme.

The insulin-degrading enzyme (IDE) cleaves numerous small peptides, including biologically active hormones and disease-related peptides. The propensity of IDE to degrade neurotoxic Aß peptides marks IDE as a potential therapeutic target for Alzheimer disease. Using a synthetic reporter based on the yeast a-factor mating pheromone precursor, which is cleaved by multiple IDE orthologs, we identified seven small molecules that stimulate rat IDE activity in vitro. Half-maximal activation of IDE by the compounds is observed in vitro in the range of 43 to 198 µM. All compounds decrease the K(m) of IDE. Four compounds activate IDE in the presence of the competing substrate insulin, which disproportionately inhibits IDE activity. Two compounds stimulate rat IDE activity in a cell-based assay, indicating that they are cell permeable. The compounds demonstrate specificity for rat IDE since they do not enhance the activities of IDE orthologs, including human IDE, and they appear specific for a-factor-based reporters since they do not enhance rat IDE-mediated cleavage of Aß-based reporters. Our results suggest that IDE activators function in the context of specific enzyme-substrate pairs, indicating that the choice of substrate must be considered in addition to target validation in IDE activator screens.