Mechanisms of Action by Which Local Anesthetics Reduce Cancer Recurrence: A Systematic Review.

BACKGROUND: Surgery in concert with anesthesia is a key part of the management of advanced-stage cancers. Anesthetic agents such as opioids and volatile anesthetics have been shown to promote recurrence in preclinical models, whereas some animal models have shown that the use of lidocaine may be beneficial in reducing cancer recurrence. The purpose of this article is to review the current literature to highlight the mechanisms of action by which local anesthetics are thought to reduce cancer recurrence. METHODS: A systematic review was conducted using the PubMed (1966 to 2018) electronic database. Search terms included "lidocaine," "ropivicaine," "procaine," "bupivicaine," "mepivicaine," "metastasis," "cancer recurrence," "angiogenesis," and "local anesthetics" in various combinations. The search yielded 146 total abstracts for initial review, 20 of which met criteria for inclusion. Theories for lidocaine's effect on cancer recurrence were recorded. All studies were reviewed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. RESULTS: Numerous mechanisms were proposed based on the local anesthetic used and the type of cancer. Mechanisms include those that are centered on endothelial growth factor receptor, voltage-gated sodium and calcium channels, transient receptor melanoplastin 7, hyperthermia, cell cycle, and demyelination. CONCLUSIONS: In vivo models suggest that local anesthetic administration leads to reduced cancer recurrence. The etiology of this effect is likely multifactorial through both inhibition of certain pathways and direct induction of apoptosis, a decrease in tumor migration, and an association with cell cycle-mediated and DNA-mediated effects. Additional research is required to further define the clinical implications.

Systematic Review of Radiofrequency Ablation and Pulsed Radiofrequency for Management of Cervicogenic Headaches.

PURPOSE OF REVIEW: Cervicogenic headache (CHA) is a secondary headache which has a source in the upper cervical spine. Many traditional analgesic choices lack good efficacy in managing the associated pain. As a result, in management of CHA, radiofrequency ablation (RFA) or pulse radiofrequency (PRF) has been tried with success. Our study investigated the use of RFA and PRF for the management of CHA. RECENT FINDINGS: In the present investigation, a review of the literature was conducted using PubMed (1966 to February 2017). The quality assessment was determined using The Cochrane Risk of Bias. After initial search and consultation with experts, 34 articles were identified for initial review and 10 articles met inclusion for review. Criteria for inclusion were primarily based on identification of articles discussing cervicogenic headaches which were previously treatment resistant and occurred without any other pathology of the craniofacial region or inciting event such as trauma. This systematic review demonstrated that RFA and PRFA provide very limited benefit in the management of CHA. At present, there is no high-quality RCT and/or strong non-RCTs to support the use of these techniques, despite numerous case reports which have demonstrated benefit. This review is one of the first to provide a comprehensive overview of the use of RFA and PRF in the management of CHA.

The Relationship Between Regional Anesthesia and Cancer: A Metaanalysis.

BACKGROUND: Some studies have suggested using epidural analgesia after cancer surgery to reduce metastasis. This article examines the relationship between regional anesthesia (RA) and cancer metastasis in an array of cancers. METHODS: We conducted a review of the literature using PubMed and included 67,577 patients across 28 studies in a metaanalysis, evaluating the hazard ratios (HRs) of overall survival, recurrence-free survival, and biochemical recurrence-free survival. RESULTS: We found no benefit to RA as it relates to cancer. The HR was 0.92 for overall survival, 1.06 for recurrence-free survival, and 1.05 for biochemical recurrence-free survival. Despite the overall analysis showing no benefit, we found some benefit when we evaluated only the randomized trials. However, we found no significant benefit of RA when we evaluated the cancers (gastrointestinal, prostate, breast, and ovarian) individually. CONCLUSION: This metaanalysis shows that RA has no overall survival, recurrence-free survival, or biochemical recurrence-free survival benefit. However, some individual studies have shown significant benefit in terms of cancer recurrence. Further, RA reduces the use of opioids, which has led to some secondary benefits. Further studies are needed to establish the benefits of RA as it relates to cancer.

Does Opioid Use Cause Angiogenesis and Metastasis?

Objective: To provide a comprehensive overview of the potential for morphine to lead to angiogenesis and metastasis. Background: Morphine is often the treatment of choice for severe cancer-related pain. Small studies have been emerging that indicate that opioids may influence angiogenesis and metastasis, but this has not yet been comprehensively synthesized. Purpose: To highlight morphine's relationship with angiogenesis and metastasis in in vitro models. Method: A review of the literature was conducted using PubMed (1966 to 2015) and Cochrane Library (1987 to 2015) electronic databases. The search, as well as consultation with experts, yielded 84 articles for initial review, 12 of which met inclusion for review. Possible theories of the underlying etiology of the metastasis and angiogenesis were recorded. Results: All studies were assessed using the PRISMA checklist. Conclusion: This systematic review demonstrates that morphine has a potential causal relationship with angiogenesis and metastasis. This is likely due to multiple etiologies, including immunosuppressive, pro-inflammatory, and pro-angiogenetic.

Current state of concussion prevention strategies: a systematic review and meta-analysis of prospective, controlled studies.

OBJECTIVE: The aim of the current review was to systematically identify, evaluate and synthesise trials that examine concussion prevention via equipment, educational programmes and training programmes. DATA SOURCES: PubMed and EBSCO host (CINAHL, MEDLINE, SPORTDiscus). ELIGIBILITY CRITERIA FOR SELECTING STUDIES: The electronic databases PubMed and EBSCO were searched using the phrases: concussion prevention equipment, concussion prevention training and concussion prevention education. Included studies utilised a prospective study design to evaluate the preventative effect of: (1) equipment, (2) training or (3) educational programmes on the incidence of concussions in comparison to a control group. DATA EXTRACTION: Demographic data and intervention methods were recorded. Intervention and control group concussion rates and superficial head injury rates were extracted and combined using random-effects relative risk meta-analysis. RESULTS: 14 studies evaluated interventions of novel protective equipment. One prospective investigation evaluated an educational programme. The relative risk of concussion for participants enrolled in the interventional arms of trials was not significantly different from that in standard practice arms (RR=0.78, 95% CI 0.55 to 1.11, χ2=1.8, p=0.17; I2=85.3%, 95% CI 71.5% to 90.8%). The relative risk of concussion for participants wearing protective equipment (ie, headgear, full face shields) relative to their counterparts wearing standard or no equipment, calculated from seven available reports, showed no effect of intervention (RR=0.82, 95% CI 0.56 to 1.20, χ2=1.06, p=0.30; I2=86.7%, 95% CI 73.3% to 91.8%). The relative risk of superficial head injury for participants wearing protective equipment relative to their counterparts, calculated from three reports, showed a significant risk reduction (RR=0.41, 95% CI 0.31 to 0.56, χ2=34.13, p<0.0001; I2=53.1%, 95% CI 0% to 85.2%). CONCLUSIONS: Prospective controlled studies indicate that certain protective equipment may prevent superficial head injury, but these items are suboptimal for concussion prevention in sport.

Risk of Secondary Injury in Younger Athletes After Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis.

BACKGROUND: Injury to the ipsilateral graft used for reconstruction of the anterior cruciate ligament (ACL) or a new injury to the contralateral ACL are disastrous outcomes after successful ACL reconstruction (ACLR), rehabilitation, and return to activity. Studies reporting ACL reinjury rates in younger active populations are emerging in the literature, but these data have not yet been comprehensively synthesized. PURPOSE: To provide a current review of the literature to evaluate age and activity level as the primary risk factors in reinjury after ACLR. STUDY DESIGN: Systematic review and meta-analysis. METHODS: A systematic review of the literature was conducted via searches in PubMed (1966 to July 2015) and EBSCO host (CINAHL, Medline, SPORTDiscus [1987 to July 2015]). After the search and consultation with experts and rating of study quality, 19 articles met inclusion for review and aggregation. Population demographic data and total reinjury (ipsilateral and contralateral) rate data were recorded from each individual study and combined using random-effects meta-analyses. Separate meta-analyses were conducted for the total population data as well as the following subsets: young age, return to sport, and young age + return to sport. RESULTS: Overall, the total second ACL reinjury rate was 15%, with an ipsilateral reinjury rate of 7% and contralateral injury rate of 8%. The secondary ACL injury rate (ipsilateral + contralateral) for patients younger than 25 years was 21%. The secondary ACL injury rate for athletes who return to a sport was also 20%. Combining these risk factors, athletes younger than 25 years who return to sport have a secondary ACL injury rate of 23%. CONCLUSION: This systematic review and meta-analysis demonstrates that younger age and a return to high level of activity are salient factors associated with secondary ACL injury. These combined data indicate that nearly 1 in 4 young athletic patients who sustain an ACL injury and return to high-risk sport will go on to sustain another ACL injury at some point in their career, and they will likely sustain it early in the return-to-play period. The high rate of secondary injury in young athletes who return to sport after ACLR equates to a 30 to 40 times greater risk of an ACL injury compared with uninjured adolescents. These data indicate that activity modification, improved rehabilitation and return-to-play guidelines, and the use of integrative neuromuscular training may help athletes more safely reintegrate into sport and reduce second injury in this at-risk population.

Is current medical education adequately preparing future physicians to manage concussion: an initial evaluation.

OBJECTIVES: In 2010, there were 2.5 million hospitalizations, emergency room visits, or deaths associated with concussions in the United States.[1] Knowledge deficits exist among physicians regarding concussion management, which can lead to severe repercussions, including poor patient outcomes, poor patient satisfaction, and potential medical-legal issues. While concussion is a prevalent condition evaluated in the medical field, medical students continue to have a knowledge deficit regarding concussion diagnosis, prognosis, medical management, and return to play guidelines. METHODS: Medical students from a mid-western medical school completed a survey on concussion diagnosis, prognosis, medical management, and return to play guidelines. RESULTS: The response rate was 40%. The data suggests that the vast majority of medical students are able to define concussion; however, most reported never having a lecture dedicated to concussion during medical school and also lacked clinical experience with acute concussion and post-concussive syndrome. There are clear areas of deficiency as noted by the inability of students to correctly identify symptoms and appropriate management of concussion. CONCLUSION: The current study indicates that at an individual, mid-western, top 50 medical school, current medical trainees may not be adequately educated to identify and manage concussion. Future research is warranted to determine the optimal guidelines to educate future physicians as it pertains to concussion diagnosis, management, prognosis, and return to play guidelines.