OBJECT Decompression surgery followed by adjuvant radiotherapy is an effective therapy for preservation or recovery of neurologic function and achieving durable local disease control in patients suffering from metastatic epidural spinal cord compression. The authors examine the outcomes of postoperative image-guided intensity-modulated radiation therapy (IG-IMRT) delivered as single-fraction or hypofractionated stereotactic radiosurgery (SRS) for achieving long-term local tumor control. METHODS A retrospective chart review identified 186 patients with epidural spinal cord compression from spinal metastases who were treated with surgical decompression, instrumentation, and postoperative radiation delivered as either single-fraction SRS (24 Gy) in 40 patients (22%), high-dose hypofractionated SRS (24-30 Gy in 3 fractions) in 37 patients (20%), or low-dose hypofractionated SRS (18-36 Gy in 5 or 6 fractions) in 109 patients (58%). The relationships between postoperative adjuvant SRS dosing and fractionation, patient characteristics, tumor histology-specific radiosensitivity, grade of epidural spinal cord compression, extent of surgical decompression, response to preoperative radiotherapy, and local tumor control were evaluated by competing risks analysis. RESULTS The total cumulative incidence of local progression was 16.4% one year after SRS. Multivariate Gray’s competing risks analysis revealed a significant improvement in local control with high-dose hypofractionated SRS (4.1% cumulative incidence of local progression at 1 year; hazard ratio = 0.12, p = 0.04) as compared to low-dose hypofractionated SRS (22.6% local progression at 1 year; HR = 1). Although univariate analysis demonstrated a trend towards greater risk of local progression for patients that failed preoperative cEBRT (22.2% local progression at 1 year, HR = 1.96, p = 0.07) compared to patients who did not receive any preoperative radiotherapy (11.2% local progression at 1 year, HR = 1), this association was not confirmed with multivariate analysis. No other variable significantly correlated with progression-free survival, including radiation sensitivity of tumor histology, grade of epidural spinal cord compression, extent of surgical decompression, or gender. CONCLUSIONS Postoperative adjuvant SRS following epidural spinal cord decompression and instrumentation is a safe and effective strategy for establishing durable local tumor control regardless of tumor histology-specific radiosensitivity. Patients who received high-dose hypofractionated SRS demonstrated one-year local progression rates less than 5% (95% CI: 0-12.2%), which were superior to the results of low-dose hypofractionated SRS. The local progression rate after single-fraction SRS was less than 10% (95% CI: 0-19.0%).

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Postoperative pain management and opioid consumption following carpal tunnel release (CTR) surgery may be influenced by many variables. To understand factors affecting opioid consumption, a prospective study was undertaken with the hypothesis that CTR performed under local anesthesia (wide awake local anesthesia with no tourniquet [WALANT]) would result in increased opioid consumption postoperatively compared with cases performed under sedation. All patients undergoing open CTR surgery were consecutively enrolled over a 6-month period. Information collected included patient demographics, surgical technique, amount and type of narcotic prescribed, number of pills taken, and type of anesthesia. 277 patients were enrolled (56% women, 44% men). On average, 21 pills were prescribed, and 4.3 pills (median = 2) were consumed. There was no difference in consumption between patients who received WALANT (78 cases) versus (198 cases) sedation (4.9 vs 3.9 pills, respectively) ( = .22). There was no difference in opioid consumption based on insurance type ( = .47) or type of narcotic ( = .85). However, more men consumed no opioids (47%) compared with women (36%) ( < .05) and older patients consumed less than younger patients ( < .05). Opioid consumption following CTR is more influenced by age and gender, and less influenced by anesthesia type, insurance type, or the type of opioid prescribed. Many more opioids were prescribed than needed, on an average of 5:1. Many patients, particularly older patients, do not require any opioid analgesia after CTR.

BackgroundAlthough quiescence (reversible cell cycle arrest) is a key part in the life history and fate of many mammalian cell types, the mechanisms of gene regulation in quiescent cells are poorly understood. We sought to clarify the role of microRNAs as regulators of the cellular functions of quiescent human fibroblasts.ResultsUsing microarrays, we discovered that the expression of the majority of profiled microRNAs differed between proliferating and quiescent fibroblasts. Fibroblasts induced into quiescence by contact inhibition or serum starvation had similar microRNA profiles, indicating common changes induced by distinct quiescence signals. By analyzing the gene expression patterns of microRNA target genes with quiescence, we discovered a strong regulatory function for miR-29, which is downregulated with quiescence. Using microarrays and immunoblotting, we confirmed that miR-29 targets genes encoding collagen and other extracellular matrix proteins and that those target genes are induced in quiescence. In addition, overexpression of miR-29 resulted in more rapid cell cycle re-entry from quiescence. We also found that let-7 and miR-125 were upregulated in quiescent cells. Overexpression of either one alone resulted in slower cell cycle re-entry from quiescence, while the combination of both together slowed cell cycle re-entry even further.ConclusionsmicroRNAs regulate key aspects of fibroblast quiescence including the proliferative state of the cells as well as their gene expression profiles, in particular, the induction of extracellular matrix proteins in quiescent fibroblasts.

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

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Background: Rates of opioid addiction and overdose continue to climb in the United States, increasing pressure on prescribers to identify solutions to decrease postoperative opioid consumption. Hand and upper extremity surgeries are high-volume surgeries with a predilection for inadvertent overprescribing. Recent investigations have shown that preoperative opioid counseling may decrease postoperative opioid consumption. In order to test this hypothesis, a prospective randomized trial was undertaken to determine the effect of preoperative opioid counseling on postoperative opioid consumption. Methods: Eligible patients undergoing outpatient upper extremity surgery were randomized to either receive preoperative opioid counseling or to receive no counseling. Surgeons were blinded to their patient’s counseling status. Preoperatively, patient demographics, surgical and prescription details were recorded. Postoperatively, patients’ pain experience including opioid consumption, pain levels, and satisfaction was recorded. Results: There were 131 total patients enrolled, with 62 in the counseling group and 69 in the control group. Patients receiving counseling consumed 11.8 pills compared to 17.4 pills in the control group ( P = .007), which translated to 93.7 Morphine Equivalent Units (MEU) in the counseling group compared to 143.2 MEU in the control group ( P = .01). There was no difference in pain scores at any time point between groups. Among all study patients a total of 3767 opioid pills were prescribed with approximately 50% left unused. Conclusion: Patients receiving preoperative counseling consumed significantly fewer opioids postoperatively. Inadvertant overprescribing remains high. Routine use of preoperative counseling should be implemented along with prescribing fewer opioids overall to prevent overprescribing.

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