A Randomized Single-Blinded Study Comparing Preoperative with Post-Mastectomy PECS Block for Post-operative Pain Management in Bilateral Mastectomy with Immediate Reconstruction.

BACKGROUND: Ultrasound-guided pectoralis muscle blocks (PECS I/II) are well established for postoperative pain control after mastectomy with reconstruction. However, optimal timing is unclear. We conducted a randomized controlled single-blinded single-institution trial comparing outcomes of block performed pre-incision versus post-mastectomy. METHOD: Patients with breast cancer undergoing bilateral mastectomy with immediate expander/implant reconstruction were randomized to receive ultrasound-guided PECS I/II either pre-incision (PreM, n = 17) or post-mastectomy and before reconstruction (PostM, n = 17). The primary outcome was the average pain score using the Numerical Rating Score during post-anesthesia care unit (PACU) and inpatient stay, with the study powered to detect a difference in mean pain score of 2. Secondary outcomes included mean pain scores on postoperative day (POD) 2, 3, 7, 14, 90, and 180; pain catastrophizing scores; narcotic requirements; PACU/inpatient length of stay; block procedure time; and complications. RESULT: No significant differences between the two groups were noted in average pain score during PACU (p = 0.57) and 24-h inpatient stay (p = 0.33), in the 2 weeks after surgery at rest (p = 0.90) or during movement (p = 0.30), or at POD 90 and 180 at rest (p = 0.42) or during movement (p = 0.31). Median duration of block procedure (PreM 7 min versus PostM 6 min, p = 0.21) did not differ. Median PACU and inpatient length of stay were the same in each group. Inpatient narcotic requirements were similar, as were length of stay and post-surgical complication rates. CONCLUSION: Intraoperative ultrasound-guided PECS I/II block administered by surgeons following mastectomy had similar outcomes to preoperative blocks. TRIAL REGISTRATION: This trial is registered with Clinical Research Information Service (NCT03653988).

Inhibitors of hydroperoxide metabolism enhance ascorbate-induced cytotoxicity.

Pharmacological ascorbate, via its oxidation, has been proposed as a pro-drug for the delivery of H(2)O(2) to tumors. Pharmacological ascorbate decreases clonogenic survival of pancreatic cancer cells, which can be reversed by treatment with scavengers of H(2)O(2). The goal of this study was to determine if inhibitors of intracellular hydroperoxide detoxification could enhance the cytotoxic effects of ascorbate. Human pancreatic cancer cells were treated with ascorbate alone or in combination with inhibitors of hydroperoxide removal including the glutathione disulfide reductase inhibitor 1,3 bis (2-chloroethyl)-1-nitrosurea (BCNU), siRNA targeted to glutathione disulfide reductase (siGR), and 2-deoxy-D-glucose (2DG), which inhibits glucose metabolism. Changes in the intracellular concentration of H(2)O(2) were determined by analysis of the rate of aminotriazole-mediated inactivation of endogenous catalase activity. Pharmacological ascorbate increased intracellular H(2)O(2) and depleted intracellular glutathione. When inhibitors of H(2)O(2) metabolism were combined with pharmacological ascorbate the increase in intracellular H(2)O(2) was amplified and cytotoxicity was enhanced. We conclude that inclusion of agents that inhibit cellular peroxide removal produced by pharmacological ascorbate leads to changes in the intracellular redox state resulting in enhanced cytotoxicity.

Specific down-regulation of annexin II expression in human cells interferes with cell proliferation.

The protein-tyrosine kinase substrate annexin II is a growth regulated gene whose expression is increased in several human cancers. While the precise function of this protein is not understood, annexin II is proposed to be involved in multiple physiological activities, including DNA synthesis and cell proliferation. Targeted disruption of the annexin II gene affects calcium signaling, tyrosine phosphorylation and apoptosis, indicating the important physiological role of this protein. We used a transient co-transfection assay to regulate annexin II expression in human HeLa, 293 and 293T cells, and measured the effects of annexin II down regulation on DNA synthesis and proliferation. Transfection of cells with an antisense annexin II vector results in inhibition of cell division and proliferation, with concomitant reduction in annexin II message and protein levels. Cellular DNA synthesis is significantly reduced in antisense transfected cells. Replication extracts made from antisense transfected cells have significantly reduced efficiency to support SV40 in vitro DNA replication, while the extracts made from sense transfected cells are fully capable of replication. Our results indicate an important role of annexin II in cellular DNA synthesis and cell proliferation.