Longitudinal Perioperative Pain Assessment in Head and Neck Cancer Surgery.

OBJECTIVE: To evaluate perioperative pain in patients undergoing major head and neck cancer surgery and identify associations between preoperative and postoperative pain characteristics. METHODS: Patients undergoing head and neck surgery with regional/free tissue transfer were enrolled. Preoperative pain and validated screens for symptoms (neuropathic pain, anxiety, depression, fibromyalgia) were assessed. Postoperatively, patients completed a pain diary for 4 weeks. RESULTS: Twenty-seven patients were enrolled. Seventy-eight percent had pain prior to surgery, and for 38%, the pain had neuropathic characteristics. Thirteen patients (48%) completed at least 2 weeks of the postoperative pain diary. Patients with moderate/severe preoperative pain report significantly greater pain scores postoperatively, though daily pain decreased at a similar linear rate for all patients. Patients with more severe preoperative pain consumed greater amounts of opioids postoperatively, and this correlated with daily postoperative pain scores. Patients who screened positive for neuropathic pain also reported worse postoperative pain. CONCLUSION: Longitudinal perioperative pain assessment in head and neck patients undergoing surgery suggests that patients with worse preoperative pain continue to endorse worse pain postoperatively and require more narcotics. Patients with preoperative neuropathic pain also report poor pain control postoperatively, suggesting an opportunity to identify these patients and intervene with empiric neuropathic pain treatment.

D-penicillamine combined with inhibitors of hydroperoxide metabolism enhances lung and breast cancer cell responses to radiation and carboplatin via H2O2-mediated oxidative stress.

D-penicillamine (DPEN), a copper chelator, has been used in the treatment of Wilson's disease, cystinuria, and rheumatoid arthritis. Recent evidence suggests that DPEN in combination with biologically relevant copper (Cu) concentrations generates H2O2 in cancer cell cultures, but the effects of this on cancer cell responses to ionizing radiation and chemotherapy are unknown. Increased steady-state levels of H2O2 were detected in MB231 breast and H1299 lung cancer cells following treatment with DPEN (100µM) and copper sulfate (15µM). Clonogenic survival demonstrated that DPEN-induced cancer cell toxicity was dependent on Cu and was significantly enhanced by depletion of glutathione [using buthionine sulfoximine (BSO)] as well as inhibition of thioredoxin reductase [using Auranofin (Au)] prior to exposure. Treatment with catalase inhibited DPEN toxicity confirming H2O2 as the toxic species. Furthermore, pretreating cancer cells with iron sucrose enhanced DPEN toxicity while treating with deferoxamine, an Fe chelator that inhibits redox cycling, inhibited DPEN toxicity. Importantly, DPEN also demonstrated selective toxicity in human breast and lung cancer cells, relative to normal untransformed human lung or mammary epithelial cells and enhanced cancer cell killing when combined with ionizing radiation or carboplatin. Consistent with the selective cancer cell toxicity, normal untransformed human lung epithelial cells had significantly lower labile iron pools than lung cancer cells. These results support the hypothesis that DPEN mediates selective cancer cell killing as well as radio-chemo-sensitization by a mechanism involving metal ion catalyzed H2O2-mediated oxidative stress and suggest that DPEN could be repurposed as an adjuvant in conventional cancer therapy.