A blinded randomized controlled trial to evaluate the use of botulinum toxin for pain control in breast reconstruction with tissue expanders.

BACKGROUND: Tissue expander placement is a common means of reconstruction after mastectomy. Many patients report significant pain and discomfort with the tissue expansion process. Because placement is subpectoral, it was hypothesized that injection of the pectoralis muscle with botulinum toxin could decrease pain associated with tissue expanders. METHODS: A prospective, randomized, double-blinded controlled trial was used to evaluate the effects of intraoperative injection of 100 U of botulinum toxin into the pectoralis muscle on one side versus placebo on the contralateral side during immediate tissue expander reconstruction after bilateral mastectomy. Patients were enrolled in the study between October 2009 and February 2012. Preoperative and postoperative pain scores, number and volume of tissue expansion, and complications were recorded. The paired t test was used to compare preoperative to postoperative changes in pain between the botulinum toxin and placebo injections. RESULTS: Twenty-three patients were enrolled in the trial. There was no statistically significant difference between preoperative to postoperative changes in the pain scores on the botulinum toxin side compared to the control side at any time point postoperatively. All pain scores trended to zero over time. CONCLUSIONS: Intraoperative injection of the pectoralis muscle with botulinum toxin is not an effective method to improve pain control in tissue expander reconstruction.

Intercellular adhesion molecule-1 mediates murine colon adenocarcinoma invasion.

BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) modulates cell-cell adhesion and is a receptor for cognate ligands on leukocytes. Upregulation of ICAM-1 has been demonstrated in malignant transformation of adenomas and is associated with poor prognosis for many malignancies. ICAM-1 is upregulated on the invasive front of pancreatic metastases and melanomas. These data suggest that the upregulated ICAM-1 expression promotes malignant progression. We hypothesize that the downregulation of ICAM-1 will mitigate tumor progression. METHODS: Mouse colon adenocarcinoma cells (MC38) were evaluated for the expression of ICAM-1 using Western immunoblot analysis. Short hairpin RNA (shRNA) transduction was used to downregulate ICAM-1. Tumor invasion determined via a modified Boyden chamber was used as a surrogate of tumor progression examining MC38 cells, MC38 ICAM-1 knockdowns, and MC38 transduced with vehicle control. The cells were cultured in full media for 24 h and serum-starved for 24 h. A total of 5 × 10(4) cells were plated and allowed to migrate for 24 h using full media with 10% fetal bovine serum as a chemoattractant. Inserts were fixed and stained with crystal violet. Blinded investigators counted the cells using a stereomicroscope. Statistical analysis was performed by analysis of variance with Fischer protected least significant difference and a P value of <0.05 was considered statistically significant. RESULTS: ICAM-1 was constitutively expressed on MC38 cells. Transduction with anti-ICAM-1 shRNA vector downregulated ICAM-1 protein expression by 30% according to the Western blot analysis (P < 0.03) and decreased ICAM-1 messenger RNA expression by 70% according to the reverse transcription-polymerase chain reaction. shRNA knockdown cells had a significant reduction in invasion >45% (P < 0.03). There were no significant differences between the invasion rates of MC38 and MC38 vehicle controls. CONCLUSIONS: Downregulation of ICAM-1 mitigates MC38 invasion. These data suggest that targeted downregulation of tumor ICAM-1 is a potential therapeutic target.

Hemoglobin-based oxygen carrier mitigates transfusion-mediated pancreas cancer progression.

BACKGROUND: Perioperative blood transfusion in pancreatic cancer patients is linked to decreased survival; however, a causal mechanism has not been determined. Previously we have shown that the plasma fraction of stored packed red blood cells (pRBCs) promotes pancreas cancer progression and associated morbidity. We hypothesize these untoward effects will be mitigated by use of a hemoglobin-based oxygen carrier (HBOC). METHODS: Cytokines and growth factors were measured in the plasma fraction from stored pRBCs and in an HBOC via cytokine array followed by formal enzyme-linked immunosorbent assay (ELISA). In an immunocompetent murine model, pancreas cancer progression was determined in vivo by bioluminescence, tumor weight, and number of metastases. RESULTS: Elevated levels of epidermal growth factor (EGF), platelet-derived growth factor BB (PDGF-BB), and regulated upon activation, normal T cell expressed and secreted (RANTES) were present in the plasma fraction of stored pRBCs, but were not found in the HBOC. Intravenous delivery of plasma fraction to mice with pancreatic cancer resulted in increased bioluminescence activity compared with mice that received HBOC. Metastatic events and pancreatic primary tumor weights were significantly higher in animals receiving plasma fraction from stored pRBCs compared with animals receiving HBOC. CONCLUSIONS: Intravenous receipt of the acellular plasma fraction of stored pRBCs promotes pancreatic cancer progression in an immunocompetent mouse model. These untoward events are mitigated by use of an HBOC.