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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 -
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 -
Current Pain and Headache Reports Jan 2020The purpose of this review is to present an overview of ilioinguinal (IL) neuralgia and evaluate the current literature. (Review)
Review
PURPOSE OF REVIEW
The purpose of this review is to present an overview of ilioinguinal (IL) neuralgia and evaluate the current literature.
RECENT FINDINGS
Treatment of IL neuralgia includes pharmacotherapies, perineural injections, radiofrequency ablation, cryoablation, neuromodulation, and neurectomy. The efficacy of these therapies varies considerably. IL neuralgia is a common pain disorder characterized by pain in the lower abdomen and upper thigh. While various modalities can be used in the treatment of IL neuralgia, the efficacy of these modalities is at times limited. Dorsal root ganglion stimulation exhibits promise in the treatment of IL neuralgia. More research is needed to better address the needs of patients suffering from this disorder.
Topics: Humans; Inguinal Canal; Neuralgia
PubMed: 31960176
DOI: 10.1007/s11916-020-0833-6 -
Annual Review of Pathology Jan 2023Nerves not only regulate the homeostasis and energetic metabolism of normal epithelial cells but also are critical for cancer, as cancer recapitulates the biology of... (Review)
Review
Nerves not only regulate the homeostasis and energetic metabolism of normal epithelial cells but also are critical for cancer, as cancer recapitulates the biology of neural regulation of epithelial tissues. Cancer cells rarely develop in denervated organs, and denervation affects tumorigenesis, in vivo and in humans. Axonogenesis occurs to supply the new malignant epithelial growth with nerves. Neurogenesis happens later, first in ganglia around organs or the spinal column and subsequently through recruitment of neuroblasts from the central nervous system. The hallmark of this stage is regulation of homeostasis and energetic metabolism. Perineural invasion is the most efficient interaction between cancer cells and nerves. The hallmark of this stage is increased proliferation and decreased apoptosis. Finally, carcinoma cells transdifferentiate into a neuronal profile in search of neural independence. The latter is the last stage in neuroepithelial interactions. Treatments for cancer must address the biology of neural regulation of cancer.
Topics: Humans; Neoplasms; Neurons
PubMed: 36323005
DOI: 10.1146/annurev-pathmechdis-031521-023248 -
Anesthesiology Mar 2022The interscalene nerve block provides analgesia for shoulder surgery. To extend block duration, provide adequate analgesia, and minimize opioid consumption, the use of... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
The interscalene nerve block provides analgesia for shoulder surgery. To extend block duration, provide adequate analgesia, and minimize opioid consumption, the use of adjuvants such as dexamethasone as well as the application of perineural liposomal bupivacaine have been proposed. This randomized, double-blinded, noninferiority trial hypothesized that perineural liposomal bupivacaine is noninferior to standard bupivacaine with perineural dexamethasone in respect to average pain scores in the first 72 h after surgery.
METHODS
A total of 112 patients undergoing ambulatory shoulder surgery were randomized into two groups. The liposomal bupivacaine group received a 15-ml premixed admixture of 10 ml of 133 mg liposomal bupivacaine and 5 ml of 0.5% bupivacaine (n = 55), while the bupivacaine with dexamethasone group received an admixture of 15 ml of 0.5% standard bupivacaine with 4 mg dexamethasone (n = 56), respectively. The primary outcome was the average numerical rating scale pain scores at rest over 72 h. The mean difference between the two groups was compared against a noninferiority margin of 1.3. Secondary outcomes were analgesic block duration, motor and sensory resolution, opioid consumption, numerical rating scale pain scores at rest and movement on postoperative days 1 to 4 and again on postoperative day 7, patient satisfaction, readiness for postanesthesia care unit discharge, and adverse events.
RESULTS
A liposomal bupivacaine group average numerical rating scale pain score over 72 h was not inferior to the bupivacaine with dexamethasone group (mean [SD], 2.4 [1.9] vs. 3.4 [1.9]; mean difference [95% CI], -1.1 [-1.8, -0.4]; P < 0.001 for noninferiority). There was no significant difference in duration of analgesia between the groups (26 [20, 42] h vs. 27 [20, 39] h; P = 0.851). Motor and sensory resolutions were similar in both groups: 27 (21, 48) h versus 27 (19, 40) h (P = 0.436) and 27 [21, 44] h versus 31 (20, 42) h (P = 0.862), respectively. There was no difference in opioid consumption, readiness for postanesthesia care unit discharge, or adverse events.
CONCLUSIONS
Interscalene nerve blocks with perineural liposomal bupivacaine provided effective analgesia similar to the perineural standard bupivacaine with dexamethasone. The results show that bupivacaine with dexamethasone can be used interchangeably with liposomal bupivacaine for analgesia after shoulder surgery.
Topics: Adult; Ambulatory Surgical Procedures; Anesthetics, Local; Anti-Inflammatory Agents; Brachial Plexus Block; Bupivacaine; Dexamethasone; Double-Blind Method; Female; Humans; Male; Middle Aged; Pain, Postoperative; Shoulder
PubMed: 35041742
DOI: 10.1097/ALN.0000000000004111 -
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 -
Frontiers in Cell and Developmental... 2022Cancerous invasion of nerves has been reported in a list of malignant tumors as a high-risk pathological feature and marker of poor disease outcome especially in... (Review)
Review
Cancerous invasion of nerves has been reported in a list of malignant tumors as a high-risk pathological feature and marker of poor disease outcome especially in neurotrophic cancers (such as in pancreas and prostate), indicating that although once neglected, nerves could have played a pivotal role in tumorigenesis and cancer progression. In colorectal cancer, perineural invasion, a specific form of tumor-nerve interaction referring to the identification of tumor cells in proximity to the nerve, has been recognized as a strong and independent prognosis predictor; denervation of autonomic nerves and enteric nerves have shown that the existence of these nerves in the gut are accompanied by promoted cancer proliferation, further supporting that nerve is a potential accomplice to shield and nurture tumor cells. However, the precise role of nerve in CRC and the pattern of interaction between CRC cells and nerve has not been unveiled yet. Here we aim to review some basic knowledge of the importance of nerves in CRC and attempt to depict a mechanistic view of tumor-nerve interaction during CRC development.
PubMed: 35223829
DOI: 10.3389/fcell.2022.766653 -
International Journal of Dermatology Jun 2022Squamous and basal cell carcinomas with perineural invasion are typically difficult to treat because of their propensity to metastasize, their aggressive nature, and the... (Review)
Review
Squamous and basal cell carcinomas with perineural invasion are typically difficult to treat because of their propensity to metastasize, their aggressive nature, and the concept of skip lesions. Perineural invasion is an under-recognized and underdiagnosed condition even though the literature points to its high rate of incidence in squamous cell carcinoma and a nonnegligible incidence rate in basal cell carcinoma. Perineural invasion has been linked to higher recurrence rates and poorer prognosis. This review has been written to aid clinicians in identifying and managing the condition as early as possible by describing the clinical and microscopic manifestations of perineural invasion.
Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Humans; Neoplasm Invasiveness; Skin Neoplasms
PubMed: 34370865
DOI: 10.1111/ijd.15817