Contamination resulting from aerosolized fluid during laparoscopic surgery.

BACKGROUND AND OBJECTIVES: Aerosolized droplets of blood can travel considerable distances on release of intra-abdominal pressure during laparoscopic surgery. This creates an environmental hazard for members of the surgical team. This study describes and provides a method of measurement of aerosolized blood contamination during evacuation of the pneumoperitoneum in laparoscopic surgery. METHODS: Samples were measured by removing a trocar from the abdomen while a pneumoperitoneum of 15 mm Hg was present. A white poster board was placed 24 inches above the incision to catch the released blood spatter. By use of machine vision, luminol fluorescence, and computerized spatial analysis, data from the boards were recorded, analyzed, and scored based on the distance, size, and quantity of particulate contamination. RESULTS: We analyzed 27 boards. Spatter was present on every board. The addition of luminol to the boards increased the amount of visible spatter. Most tests created <1000 blood spatters. Fluids are typically ejected as a fine mist. Every test included at least 1 blood spatter. The range of the average blood spatter size was 0.53×10(-3) to 7.11×10(-3) sq in. The amount of spatter detected did not show any apparent correlation with the patient's body mass index, the estimated blood loss, or the type of operation performed. CONCLUSIONS: Evacuation of the pneumoperitoneum during laparoscopic surgery results in consistent contamination. Most blood spatter is not visible to the naked eye. Our results suggest that all surgical participants should wear appropriate protective barriers and conscious measures should be undertaken to prevent environmental contamination during pneumoperitoneal evacuation.

Evasion mechanisms to Igf1r inhibition in rhabdomyosarcoma.

Inhibition of the insulin-like growth factor 1 receptor (Igf1r) is an approach being taken in clinical trials to overcome the dismal outcome for metastatic alveolar rhabdomyosarcoma (ARMS), an aggressive muscle cancer of children and young adults. In our study, we address the potential mechanism(s) of Igf1r inhibitor resistance that might be anticipated for patients. Using a genetically engineered mouse model of ARMS, validated for active Igf1r signaling, we show that the prototypic Igf1r inhibitor NVP-AEW541 can inhibit cell growth and induce apoptosis in vitro in association with decreased Akt and Mapk phosphorylation. However, drug resistance in vivo is more common and is accompanied by Igf1r overexpression, Mapk reactivation, and Her2 overexpression. Her2 is found to form heterodimers with Igf1r in resistant primary tumor cell cultures, and stimulation with Igf2 leads to Her2 phosphorylation. The Her2 inhibitor lapatinib cooperates with NVP-AEW541 to reduce Igf1r phosphorylation and to inhibit cell growth even though lapatinib alone has little effect on growth. These results point to the potential therapeutic importance of simultaneous targeting of Igf1r and Her2 to abrogate resistance.

Functional evaluation of therapeutic response for a mouse model of medulloblastoma.

Medulloblastoma is an aggressive childhood cerebellar tumor. We recently reported a mouse model with conditional deletion of Patched1 gene that recapitulates many characteristics of the human medulloblastoma. Qualitative symptoms observed in the mouse model include irregular stride length, impaired cranial nerve function and decreased motor coordination and performance. In our current study, several quantitative behavioral assays including a mouse rotarod, a forced air challenge, a screen inversion test, a horizontal wire test, and stride length analysis were evaluated to determine the most sensitive and cost-effective functional assay for impaired neuromotor behavior associated with disease progression. Magnetic resonance imaging (MRI) was used to confirm and monitor tumor growth and as an anatomical biomarker for therapeutic response. Wild type mice or medulloblastoma-prone, conditional Patched1 knockout mice were observed by behavioral assays and MRI from postnatal weeks 3-6. Bortezomib treatment was administered during this period and therapeutic response was assessed using cerebellar volumes at the end of treatment. Of the behavioral tests assessed in this study, stride length analysis was best able to detect differences between tumor-prone mice and wild type mice as early as postnatal day 37 (P=0.003). Significant differences between stride lengths of bortezomib treated and control tumor-bearing mice could be detected as early as postnatal day 42 (P=0.020). Cerebellar volumes measured by MRI at the end of treatment validated the therapeutic effects seen by behavioral tests (P=0.03). These findings suggest that stride length analysis may serve as one of the more sensitive and cost-effective method for assessing new therapeutic compounds in this and other preclinical model of brain tumors.