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Biomedicine & Pharmacotherapy =... Nov 2022Perineural invasion (PNI) is the process of neoplastic invasion of peripheral nerves and is considered to be the fifth mode of cancer metastasis. PNI has been detected... (Review)
Review
Perineural invasion (PNI) is the process of neoplastic invasion of peripheral nerves and is considered to be the fifth mode of cancer metastasis. PNI has been detected in head and neck tumors and pancreatic, prostate, bile duct, gastric, and colorectal cancers. It leads to poor prognostic outcomes and high local recurrence rates. Despite the increasing number of studies on PNI, targeted therapeutic modalities have not been proposed. The identification of PNI-related biomarkers would facilitate the non-invasive and early diagnosis of cancers, the establishment of prognostic panels, and the development of targeted therapeutic approaches. In this review, we compile information on the molecular mediators involved in PNI-associated cancers. The expression and prognostic significance of molecular mediators and their receptors in PNI-associated cancers are analyzed, and the possible mechanisms of action of these mediators in PNI are explored, as well as the association of cells in the microenvironment where PNI occurs.
Topics: Male; Humans; Neoplasm Invasiveness; Peripheral Nerves; Head and Neck Neoplasms; Biomarkers; Retrospective Studies; Tumor Microenvironment
PubMed: 36095958
DOI: 10.1016/j.biopha.2022.113691 -
Cancer Communications (London, England) Aug 2021Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignant disease with a unique tumor microenvironment surrounded by an interlaced network of cancer and... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignant disease with a unique tumor microenvironment surrounded by an interlaced network of cancer and noncancerous cells. Recent works have revealed that the dynamic interaction between cancer cells and neuronal cells leads to perineural invasion (PNI), a clinical pathological feature of PDAC. The formation and function of PNI are dually regulated by molecular (e.g., involving neurotrophins, cytokines, chemokines, and neurotransmitters), metabolic (e.g., serine metabolism), and cellular mechanisms (e.g., involving Schwann cells, stromal cells, T cells, and macrophages). Such integrated mechanisms of PNI not only support tumor development, growth, invasion, and metastasis but also mediate the formation of pain, all of which are closely related to poor disease prognosis in PDAC. This review details the modulation, signaling pathways, detection, and clinical relevance of PNI and highlights the opportunities for further exploration that may benefit PDAC patients.
Topics: Carcinoma, Pancreatic Ductal; Humans; Neoplasm Invasiveness; Pancreatic Neoplasms; Signal Transduction; Tumor Microenvironment
PubMed: 34264020
DOI: 10.1002/cac2.12188 -
Anaesthesia Jan 2021Moderate-to-severe postoperative pain persists for longer than the duration of single-shot peripheral nerve blocks and hence continues to be a problem even with the... (Review)
Review
Moderate-to-severe postoperative pain persists for longer than the duration of single-shot peripheral nerve blocks and hence continues to be a problem even with the routine use of regional anaesthesia techniques. The administration of local anaesthetic adjuncts, defined as the concomitant intravenous or perineural injection of one or more pharmacological agents, is an attractive and technically simple strategy to potentially extend the benefits of peripheral nerve blockade beyond the conventional maximum of 8-14 hours. Historical local anaesthetic adjuncts include perineural adrenaline that has been demonstrated to increase the mean duration of analgesia by as little as just over 1 hour. Of the novel local anaesthetic adjuncts, dexmedetomidine and dexamethasone have best demonstrated the capacity to considerably improve the duration of blocks. Perineural dexmedetomidine and dexamethasone increase the mean duration of analgesia by up to 6 hour and 8 hour, respectively, when combined with long-acting local anaesthetics. The evidence for the safety of these local anaesthetic adjuncts continues to accumulate, although the findings of a neurotoxic effect with perineural dexmedetomidine during in-vitro studies are conflicting. Neither perineural dexmedetomidine nor dexamethasone fulfils all the criteria of the ideal local anaesthetic adjunct. Dexmedetomidine is limited by side-effects such as bradycardia, hypotension and sedation, and dexamethasone slightly increases glycaemia. In view of the concerns related to localised nerve and muscle injury and the lack of consistent evidence for the superiority of the perineural vs. systemic route of administration, we recommend the off-label use of systemic dexamethasone as a local anaesthetic adjunct in a dose of 0.1-0.2 mg.kg for all patients undergoing surgery associated with significant postoperative pain.
Topics: Anesthesia, Conduction; Anesthetics, Local; Conscious Sedation; Humans; Hypnotics and Sedatives; Nerve Block; Peripheral Nerves
PubMed: 33426668
DOI: 10.1111/anae.15245 -
The Cochrane Database of Systematic... Nov 2017Peripheral nerve block (infiltration of local anaesthetic around a nerve) is used for anaesthesia or analgesia. A limitation to its use for postoperative analgesia is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Peripheral nerve block (infiltration of local anaesthetic around a nerve) is used for anaesthesia or analgesia. A limitation to its use for postoperative analgesia is that the analgesic effect lasts only a few hours, after which moderate to severe pain at the surgical site may result in the need for alternative analgesic therapy. Several adjuvants have been used to prolong the analgesic duration of peripheral nerve block, including perineural or intravenous dexamethasone.
OBJECTIVES
To evaluate the comparative efficacy and safety of perineural dexamethasone versus placebo, intravenous dexamethasone versus placebo, and perineural dexamethasone versus intravenous dexamethasone when added to peripheral nerve block for postoperative pain control in people undergoing surgery.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, DARE, Web of Science and Scopus from inception to 25 April 2017. We also searched trial registry databases, Google Scholar and meeting abstracts from the American Society of Anesthesiologists, the Canadian Anesthesiologists' Society, the American Society of Regional Anesthesia, and the European Society of Regional Anaesthesia.
SELECTION CRITERIA
We included all randomized controlled trials (RCTs) comparing perineural dexamethasone with placebo, intravenous dexamethasone with placebo, or perineural dexamethasone with intravenous dexamethasone in participants receiving peripheral nerve block for upper or lower limb surgery.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included 35 trials of 2702 participants aged 15 to 78 years; 33 studies enrolled participants undergoing upper limb surgery and two undergoing lower limb surgery. Risk of bias was low in 13 studies and high/unclear in 22. Perineural dexamethasone versus placeboDuration of sensory block was significantly longer in the perineural dexamethasone group compared with placebo (mean difference (MD) 6.70 hours, 95% confidence interval (CI) 5.54 to 7.85; participants1625; studies 27). Postoperative pain intensity at 12 and 24 hours was significantly lower in the perineural dexamethasone group compared with control (MD -2.08, 95% CI -2.63 to -1.53; participants 257; studies 5) and (MD -1.63, 95% CI -2.34 to -0.93; participants 469; studies 9), respectively. There was no significant difference at 48 hours (MD -0.61, 95% CI -1.24 to 0.03; participants 296; studies 4). The quality of evidence is very low for postoperative pain intensity at 12 hours and low for the remaining outcomes. Cumulative 24-hour postoperative opioid consumption was significantly lower in the perineural dexamethasone group compared with placebo (MD 19.25 mg, 95% CI 5.99 to 32.51; participants 380; studies 6). Intravenous dexamethasone versus placeboDuration of sensory block was significantly longer in the intravenous dexamethasone group compared with placebo (MD 6.21, 95% CI 3.53 to 8.88; participants 499; studies 8). Postoperative pain intensity at 12 and 24 hours was significantly lower in the intravenous dexamethasone group compared with placebo (MD -1.24, 95% CI -2.44 to -0.04; participants 162; studies 3) and (MD -1.26, 95% CI -2.23 to -0.29; participants 257; studies 5), respectively. There was no significant difference at 48 hours (MD -0.21, 95% CI -0.83 to 0.41; participants 172; studies 3). The quality of evidence is moderate for duration of sensory block and postoperative pain intensity at 24 hours, and low for the remaining outcomes. Cumulative 24-hour postoperative opioid consumption was significantly lower in the intravenous dexamethasone group compared with placebo (MD -6.58 mg, 95% CI -10.56 to -2.60; participants 287; studies 5). Perinerual versus intravenous dexamethasoneDuration of sensory block was significantly longer in the perineural dexamethasone group compared with intravenous by three hours (MD 3.14 hours, 95% CI 1.68 to 4.59; participants 720; studies 9). We found that postoperative pain intensity at 12 hours and 24 hours was significantly lower in the perineural dexamethasone group compared with intravenous, however, the MD did not surpass our pre-determined minimally important difference of 1.2 on the Visual Analgue Scale/Numerical Rating Scale, therefore the results are not clinically significant (MD -1.01, 95% CI -1.51 to -0.50; participants 217; studies 3) and (MD -0.77, 95% CI -1.47 to -0.08; participants 309; studies 5), respectively. There was no significant difference in severity of postoperative pain at 48 hours (MD 0.13, 95% CI -0.35 to 0.61; participants 227; studies 3). The quality of evidence is moderate for duration of sensory block and postoperative pain intensity at 24 hours, and low for the remaining outcomes. There was no difference in cumulative postoperative 24-hour opioid consumption (MD -3.87 mg, 95% CI -9.93 to 2.19; participants 242; studies 4). Incidence of severe adverse eventsFive serious adverse events were reported. One block-related event (pneumothorax) occurred in one participant in a trial comparing perineural dexamethasone and placebo; however group allocation was not reported. Four non-block-related events occurred in two trials comparing perineural dexamethasone, intravenous dexamethasone and placebo. Two participants in the placebo group required hospitalization within one week of surgery; one for a fall and one for a bowel infection. One participant in the placebo group developed Complex Regional Pain Syndrome Type I and one in the intravenous dexamethasone group developed pneumonia. The quality of evidence is very low due to the sparse number of events.
AUTHORS' CONCLUSIONS
Low- to moderate-quality evidence suggests that when used as an adjuvant to peripheral nerve block in upper limb surgery, both perineural and intravenous dexamethasone may prolong duration of sensory block and are effective in reducing postoperative pain intensity and opioid consumption. There is not enough evidence to determine the effectiveness of dexamethasone as an adjuvant to peripheral nerve block in lower limb surgeries and there is no evidence in children. The results of our review may not apply to participants at risk of dexamethasone-related adverse events for whom clinical trials would probably be unsafe.There is not enough evidence to determine the effectiveness of dexamethasone as an adjuvant to peripheral nerve block in lower limb surgeries and there is no evidence in children. The results of our review may not be apply to participants who at risk of dexamethasone-related adverse events for whom clinical trials would probably be unsafe. The nine ongoing trials registered at ClinicalTrials.gov may change the results of this review.
Topics: Anesthetics, Local; Arm; Dexamethasone; Glucocorticoids; Humans; Injections, Intravenous; Leg; Nerve Block; Neuromuscular Blocking Agents; Pain, Postoperative; Randomized Controlled Trials as Topic; Time Factors
PubMed: 29121400
DOI: 10.1002/14651858.CD011770.pub2 -
Cancer Research May 2020Perineural invasion is a common feature of pancreatic ductal adenocarcinoma (PDAC). Here, we investigated the effect of perineural invasion on the microenvironment and...
Perineural invasion is a common feature of pancreatic ductal adenocarcinoma (PDAC). Here, we investigated the effect of perineural invasion on the microenvironment and how this affects PDAC progression. Transcriptome expression profiles of PDAC tissues with different perineural invasion status were compared, and the intratumoral T-cell density and levels of neurotransmitters in these tissues were assessed. Perineural invasion was associated with impaired immune responses characterized by decreased CD8 T and Th1 cells, and increased Th2 cells. Acetylcholine levels were elevated in severe perineural invasion. Acetylcholine impaired the ability of PDAC cells to recruit CD8 T cells via HDAC1-mediated suppression of CCL5. Moreover, acetylcholine directly inhibited IFNγ production by CD8 T cells in a dose-dependent manner and favored Th2 over Th1 differentiation. Furthermore, hyperactivation of cholinergic signaling enhanced tumor growth by suppressing the intratumoral T-cell response in an orthotopic PDAC model. Conversely, blocking perineural invasion with bilateral subdiaphragmatic vagotomy in tumor-bearing mice was associated with an increase in CD8 T cells, an elevated Th1/Th2 ratio, and improved survival. In conclusion, perineural invasion-triggered cholinergic signaling favors tumor growth by promoting an immune-suppressive microenvironment characterized by impaired CD8 T-cell infiltration and a reduced Th1/Th2 ratio. SIGNIFICANCE: These findings provide a promising therapeutic strategy to modulate the immunosuppressive microenvironment of pancreatic ductal adenocarcinoma with severe perineural invasion.
Topics: Acetylcholine; Animals; Carcinoma, Pancreatic Ductal; Humans; Lymphocytes, Tumor-Infiltrating; Mice; Neoplasm Invasiveness; Pancreatic Neoplasms; Signal Transduction; Tumor Microenvironment
PubMed: 32098780
DOI: 10.1158/0008-5472.CAN-19-2689 -
Clinical Oncology (Royal College of... Dec 2018Postoperative radiotherapy is the standard of care for resected major salivary cancers that are at risk of locoregional recurrence. Of the various histological subtypes,...
AIMS
Postoperative radiotherapy is the standard of care for resected major salivary cancers that are at risk of locoregional recurrence. Of the various histological subtypes, perineural invasion is most common in adenoidcystic carcinomas of the three major salivary glands - parotid, submandibular and sublingual. The clinical target volume (CTV) for these cases must include the relevant cranial nerve pathways at risk. A contouring atlas was devised for delineation of the CTV of the nerves supplying the major salivary glands.
MATERIALS AND METHODS
Using standard anatomy texts and e-anatomy sources the nerves supplying the major salivary glands were identified. Subsequently the pathways of the nerves were drawn on an archived patient's planning computed tomography scan.
RESULTS
The innervation of the major salivary glands has been identified and studied. Both bone and soft tissue CTVs have been delineated. A full set of images and CTVs of all the relevant transverse computed tomography slices has been archived, a number of which are printed in this article.
CONCLUSIONS
Variation in CTV delineation is a recognised problem in a variety of anatomic sites. Guidelines and atlases can standardise practice and may improve the safety and efficacy of therapy. An atlas has been generated to guide clinicians in delineating the CTVs for perineural spread in major salivary gland cancers.
Topics: Humans; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Peripheral Nerves; Practice Guidelines as Topic; Prognosis; Salivary Gland Neoplasms; Tomography, X-Ray Computed
PubMed: 30224202
DOI: 10.1016/j.clon.2018.08.018 -
Polski Merkuriusz Lekarski : Organ... Nov 2018Perineural cyst (Tarlov cyst) is a lesion in a form of fluid-filled sacks, usually located within the nerve root sheath at the posterior root of a spinal nerve, whose... (Review)
Review
Perineural cyst (Tarlov cyst) is a lesion in a form of fluid-filled sacks, usually located within the nerve root sheath at the posterior root of a spinal nerve, whose wall is formed by: endoneurium, peripheral nerve fibers and ganglion cells and areolar tissue. Depending on the studied population, the frequency of lesion occurence was estimated at 1.5- 13.2%, with its significant majority occuring in women. Cyst development may be the result of ischemia, hemorrhage, inflammation or trauma. Cysts are usually asymptomatic theefore they are likely to bo detected accidentally. However, in approximately 1/4 of the cases, the cyst puts so much pressure on the nerve and the neighbouring nerve roots that it becomes symptomatic (causes pain). The presence of clinical symptoms may be an indication for conservative treatment (i.e. analgesics, rehablitation, cyst puncture) or surgery (usually laminectomy).
Topics: Female; Humans; Male; Tarlov Cysts
PubMed: 30531671
DOI: No ID Found -
Journal of Neurological Surgery. Part... Apr 2016The perineural space is a compartment located between the nerve axons, supporting cells and tissues, and the epineural fibrous sheath. Tumor cells invade this space in... (Review)
Review
The perineural space is a compartment located between the nerve axons, supporting cells and tissues, and the epineural fibrous sheath. Tumor cells invade this space in response to a complex interplay of trophic factors in the local microenviroment. This attraction of tumor cells to nerves is referred to as neurotropism. The perineural space provides a conduit for tumor spread beyond the primary site of tumor occurrence. Perineural tumor growth is of two types: perineural invasion, affecting small unnamed nerves; and perineural spread, affecting larger, named nerves and presenting with clinical symptoms related to the involved nerve. Both forms of perineural tumor growth represent an adverse prognostic feature and are an essential element of the histopathologic reporting of malignancies of the head and neck region. Perineural spread is associated with decreased overall survival. Endoneurial invasion frequently accompanies perineural spread. The epineurium is more resistant to invasion and represents an important barrier to tumor spread. Immunohistochemical stains such as broad-spectrum keratin can aid in defining the proximal extent of perineural tumor spread.
PubMed: 27123388
DOI: 10.1055/s-0036-1571837 -
Operative Orthopadie Und Traumatologie Feb 2020The so-called ankle block represents a local anesthesia form which enables easy performance of all surgical procedures of the foot and ankle. (Review)
Review
OBJECTIVE
The so-called ankle block represents a local anesthesia form which enables easy performance of all surgical procedures of the foot and ankle.
INDICATIONS
Interventions distal to the medial and lateral malleoli.
CONTRAINDICATIONS
Acute and chronic infections in the area of injection; allergy to the local anesthesia.
SURGICAL TECHNIQUE
All five sensory foot nerves are blocked. The two deep lying nerves, the tibial nerve and the deep fibular nerve, can be directly anesthetized perineurally using anatomical landmarks. The other three nerves are subcutaneously infiltrated near their branches.
RESULTS
The success rate ranges from 88 to 94%; smaller areas may also be further blocked intraoperatively. The ankle block is a cost-effective procedure which can also be performed without problems in multimorbid patients due to its minor side effects.
Topics: Ankle; Foot; Humans; Nerve Block; Tibial Nerve; Treatment Outcome
PubMed: 31940050
DOI: 10.1007/s00064-019-00634-x -
Abdominal Radiology (New York) Feb 2018Pancreatic ductal adenocarcinoma continues to be a highly lethal disease, despite advances in modern medicine. Curative surgical options continue to carry significant... (Review)
Review
Pancreatic ductal adenocarcinoma continues to be a highly lethal disease, despite advances in modern medicine. Curative surgical options continue to carry significant morbidity and offer little improvement in overall 5-year survival. Currently, imaging plays an essential role in the pre-operative evaluation of patients who are undergoing evaluation for resection. However, some pancreatic cancers have particularly aggressive biology, despite appearing resectable by conventional imaging criteria. Imaging biomarkers that serve as surrogates for tumors with such aggressive phenotype have been recently described, namely duodenal invasion and extrapancreatic perineural invasion. In this pictorial review, we will summarize key concepts of extrapancreatic perineural invasion, describe its association with a poor prognosis, and highlight the role of imaging in its detection.
Topics: Adenocarcinoma; Carcinoma, Pancreatic Ductal; Contrast Media; Humans; Imaging, Three-Dimensional; Iopamidol; Neoplasm Invasiveness; Pancreatic Neoplasms; Peripheral Nervous System Neoplasms; Prognosis; Radiographic Image Interpretation, Computer-Assisted; Tomography, X-Ray Computed
PubMed: 28980054
DOI: 10.1007/s00261-017-1343-9