Objective. More than one million people each year in the United States are diagnosed with cancer. Surgery is considered curative, but the perioperative phase represents a vulnerable period for residual disease to spread. Regional anesthesia has been proposed to reduce the incidence of recurrence by attenuating the sympathetic nervous system's response during surgery, reducing opioid requirements thus diminishing their immunosuppressant effects, and providing antitumor and antiinflammatory effects directly through systemic local anesthetic action. In this article, we present a description of the perioperative period, a summary of the proposed hypotheses and available literature on the effects of regional anesthesia on cancer recurrence, and put regional anesthesia in context in regard to its potential role in reducing cancer recurrence during the perioperative period.Methods. A literature review was conducted through PubMed by examining the following topics: effects of surgery on tumor progression, roles of multiple perioperative variables (analgesics, hypothermia, blood transfusion, beta-blockade) in cancer recurrence, and available in vitro, animal, and human studies regarding the effects of regional anesthesia on cancer recurrence.Results. in vitro, animal and human retrospective studies suppport the hypothesis that in certain types of cancer, regional anesthesia may be associated with lower recurrence rates. A few well-planned human randomized clinical trials are currently under way that may provide more solid evidence to substantiate or refute the benefits of regional anesthesia in reducing cancer recurrence.Conclusions. The benefits of regional anesthesia in reducing cancer recurrence have a sound theoretical basis and, in certain cancers, are supported by the existing body of literature. This article outlines the current state of our knowledge on the relationship between cancer progression and regional analgesia.

Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background There is confusion regarding the spread of intraneurally injected local anesthetic agents during regional anesthesia. The aim of this research was to deliberately inject a marker that does not leave the neural compartment into which it is injected, and then to study the longitudinal and circumferential spread and possible pathways of intraneural spread. Methods After institutional review board approval, we intraneurally injected 20 and 5 ml of heparinized blood solution under ultrasound guidance into 12 sciatic nerves in the popliteal fossa and 10 median nerves, respectively, of eight fresh, unembalmed cadavers using standard 22-gauge “D” needles, mimicking the blocks in clinical conditions. Ultrasound evidence of nerve swelling confirmed intraneural injection. Samples of the nerves were then examined under light and scanning electron microscopy. Results Extrafascicular spread was observed in all the adipocyte-containing neural compartments of the 664 cross-section samples we examined, but intrafascicular spread was seen in only 6 cross-sections of two nerves. None of the epineurium, perineurium, or neural components were disrupted in any of the samples. Spread between the layers of the perineurium was a route of spread that included the perineurium surrounding the fascicles and the perineurium that formed incomplete septa in the fascicles. Similar to the endoneurium proper, subepineural compartments that did not contain any fat cells did not reveal any spread of heparinized blood solution cells. No “perineural” spaces were observed within the endoneurium. We also did not observe any true intrafascicular spread. Conclusions After deliberate intraneural injection, longitudinal and circumferential extrafascicular spread occurred in all instances in the neural compartments that contained adipocytes, but not in the relatively solid endoneurium of the fascicles.

Objective To better understand the unexpected spread of contrast medium observed by conventional fluoroscopic X‐ray images during standard neuraxial techniques used in the treatment of pain. The support of 3D reconstruction of MRI images of structures within the lumbar spine was used to better understand the space of Okada. Methods Lumbar facet joint and epidural corticosteroid injections in five patients under fluoroscopic guidance with loss of resistance to air or saline to identify the facet joints or epidural space. Next, in a retrospective study, the authors examined the retrodural space of Okada and the neighboring tissues with 3D reconstruction of spinal MRIs of seven patients without any demonstrable spinal pathology to better understand the characteristics of the space of Okada. Results Contrast medium spread to the ipsilateral and contralateral sides was observed in five patients. The contralateral spread was thought to be through the retrodural space of Okada, which is a potential space between the anterior surface of the vertebral lamina and the posterior surface of the ligamentum flavum. It facilitates communication between the contralateral articular facet joints of the spine. Conclusions This study provides new evidence for the existence of the space of Okada where an unexpected contralateral spread occurred following facet joint and attempted epidural injection. The 3D reconstructions of MRIs may help us better understand the nature of the retrodural space of Okada and its clinical implications.