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Cancers Jun 2019Perineural invasion (PNI) is defined as the presence of neoplastic cells along nerves and/or within the different layers of nervous fibers: epineural, perineural and... (Review)
Review
Perineural invasion (PNI) is defined as the presence of neoplastic cells along nerves and/or within the different layers of nervous fibers: epineural, perineural and endoneural spaces. In pancreatic cancer-particularly in pancreatic ductal adenocarcinoma (PDAC)-PNI has a prevalence between 70 and 100%, surpassing any other solid tumor. PNI has been detected in the early stages of pancreatic cancer and has been associated with pain, increased tumor recurrence and diminished overall survival. Such an early, invasive and recurrent phenomenon is probably crucial for tumor growth and metastasis. PNI is a still not a uniformly characterized event; usually it is described only dichotomously ("present" or "absent"). Recently, a more detailed scoring system for PNI has been proposed, though not specific for pancreatic cancer. Previous studies have implicated several molecules and pathways in PNI, among which are secreted neurotrophins, chemokines and inflammatory cells. However, the mechanisms underlying PNI are poorly understood and several aspects are actively being investigated. In this review, we will discuss the main molecules and signaling pathways implicated in PNI and their roles in the PDAC.
PubMed: 31248001
DOI: 10.3390/cancers11070893 -
Aesthetic Surgery Journal. Open Forum 2023Treating facial aging with CO lasering or microneedling are cornerstones of facial rejuvenation. Skin rejuvenation utilizing thermal and mechanical treatments have...
BACKGROUND
Treating facial aging with CO lasering or microneedling are cornerstones of facial rejuvenation. Skin rejuvenation utilizing thermal and mechanical treatments have historically been considered too injurious to be combined at a single setting. Autologous nanofat has been shown to deliver wound healing properties. We investigated the safety and efficacy of co-terminus CO lasering and microneedling to resolve fine lines and rhytids in facial skin with addition of autologous nanofat to aid in recovery.
OBJECTIVES
Combination treatments may result in better results with faster recovery. We investigated the safety and efficacy of co-terminus CO lasering and microneedling to resolve fine lines and rhytids in facial skin with addition of autologous nanofat to aid in recovery.
METHODS
Twenty-three patients underwent facial treatment with CO lasering followed by microneedling and application of autologous nanofat (LaMiNa). One volunteer patient had tissue biopsies of treatment areas to demonstrate histologic tissue level changes.
RESULTS
All patients verbally reported no pain (Numerical Rating System 0-10) following procedure and had rapid recovery within an average of 5 days. Pathology results demonstrated that CO and microneedling had persistent epidermal disruption and perineural inflammation at 4 days, while the introduction of autologous nanofat at the time of CO and microneedling resulted in full recovery of epidermis and resolution of perineural inflammation.
CONCLUSIONS
Triple therapy (LaMiNa) with thermal CO remodeling and mechanical microneedling penetration have accelerated and pain-free recovery with the addition of autologous nanofat. Histologic analysis reveals that epidermal recovery is accelerated and perineural inflammation is reduced with the addition of autologous nanofat following skin remodeling from combined CO and microneedling.
PubMed: 37089168
DOI: 10.1093/asjof/ojad028 -
Surgical Neurology International 2020Perineural invasion (PNI) and spread are one of the grimmest prognostic factors associated with primary skin and head-and-neck cancers, yet remain an often confused, and... (Review)
Review
BACKGROUND
Perineural invasion (PNI) and spread are one of the grimmest prognostic factors associated with primary skin and head-and-neck cancers, yet remain an often confused, and underreported, phenomenon. Adding complexity to reaching a diagnosis and treating perineural spread (PNS) is the finding that patients may have no known primary tumor, history of skin cancer, and/or incidental PNI in the primary tumor. These delays in diagnosis and treatment are further compounded by an already slow disease process and often require multidisciplinary care with combinations of stereotactic radiosurgery, surgical resection, and novel treatments such as checkpoint inhibitors.
METHODS
Six patients with metastatic cancer to the cranial nerves who underwent Gamma Knife radiosurgery (GKRS) treatment were chosen for retrospective analysis. This information included age, gender, any past surgeries (both stereotactic and regular surgery), dose of radiation and volume of the tumor treated in the GKRS, date of PNS, comorbidities, the patient follow-up, and pre- and post-GKRS imaging. The goal of the follow-up with radiographing imaging was to assess the efficacy of GKSS.
RESULTS
The clinical course of six patients with PNS is presented. Patients followed variable courses with mixed outcomes: two patients remain living, one was lost to follow-up, and three expired with a median survival of 12 months from date of diagnosis. Patients at our institution are ideally followed for life.
CONCLUSION
Given the morbidity and mortality of PNS of cancer, time is limited, and further understanding is required to improve outcomes. Here, we provide a case series of patients with PNS treated with stereotactic radiosurgery, discuss their clinical courses, and review the known literature.
PubMed: 32874709
DOI: 10.25259/SNI_146_2020 -
American Journal of Cancer Research 2019Perineural invasion (PNI) can be found in a variety of malignant tumors. It is a sign of tumor metastasis and invasion and portends the poor prognosis of patients. The... (Review)
Review
Perineural invasion (PNI) can be found in a variety of malignant tumors. It is a sign of tumor metastasis and invasion and portends the poor prognosis of patients. The pathological description and clinical significance of PNI are clearly understood, but exploration of the underlying molecular mechanism is ongoing. It was previously thought that the low-resistance channel in the anatomic region led to the occurrence of PNI. However, with rapid development of precision medicine and molecular biology, we have gradually realized that the occurrence of PNI is not the result of a single factor. The latest study suggests that PNI of cancer is a continuous and multistep process. A specific peripheral microenvironment, also called the perineural niche, is formed by neural cells, supporting cells, recruited inflammatory cells, altered extracellular matrix, blood vessels, and immune components in the background of carcinoma. Various soluble signaling molecules and their receptors comprise a complex signal network, which achieves the interaction between nerve and tumor. Nerve cells and tumor cells can interact directly or through the opening and closing of the signal transduction pathways and/or the recognition and response of the ligands and receptors. The information is transferred to the targets accurately and effectively, leading to the specific interactions between the nerve cells and the malignant tumor cells. PNI occurs through changes in nerve cells and supporting cells in the background of cancer; change and migration of the perineural matrix; enhancement of the viability, mobility, and invasiveness of the tumor cells; injury and regeneration of nerve cells; interaction, chemotactic movement, contact, and adherence of the nerve cells and the tumor cells; escape from autophagy, apoptosis, and immunological surveillance of tumor cells; and so on. Certainly, exploring the mechanism of PNI clearly has great significance for blocking tumor progression and improving patient survival. The current review aims to elucidate the cellular and molecular mechanisms of PNI, which may help us find a strategy for improving the prognosis of malignant tumors.
PubMed: 30755808
DOI: No ID Found -
American Journal of Stem Cells 2021Most epithelium tissues continuously undergo self-renewal through proliferation and differentiation of epithelial stem cells (known as homeostasis), within a specialized... (Review)
Review
Most epithelium tissues continuously undergo self-renewal through proliferation and differentiation of epithelial stem cells (known as homeostasis), within a specialized stem cell niche. In highly innervated epithelium, peripheral nerves compose perineural niche and support stem cell homeostasis by releasing a variety of neurotransmitters, hormones, and growth factors and supplying trophic factors to the stem cells. Emerging evidence has shown that both sensory and motor nerves can regulate the fate of epithelial stem cells, thus influencing epithelium homeostasis. Understanding the mechanism of crosstalk between epithelial stem cells and neurons will reveal the important role of the perineural niche in physiological and pathological conditions. Herein, we review recent discoveries of the perineural niche in epithelium mainly in tissue homeostasis, with a limited touch in wound repair and pathogenesis.
PubMed: 34849302
DOI: No ID Found -
Journal of Korean Medical Science Jun 2023Interscalene brachial plexus block (ISB) is a common regional technique to manage acute postoperative pain for arthroscopic rotator cuff tear repair. However, rebound... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Interscalene brachial plexus block (ISB) is a common regional technique to manage acute postoperative pain for arthroscopic rotator cuff tear repair. However, rebound pain may compromise its overall benefit. Our aim was to investigate the primary hypothesis that perineural and intravenous dexamethasone have different effects on rebound pain after resolution of ISB for arthroscopic rotator cuff tear repair.
METHODS
Patients aged ≥ 20 years scheduled for elective arthroscopic rotator cuff tear repair under general anesthesia with preoperative ISB were included. The participants were randomized to receive dexamethasone either perineurally (perineural group) or intravenously (intravenous group). In the perineural group, patients received ISB with 12 mL of 0.5% ropivacaine containing 5 mg of dexamethasone; simultaneously, 1 mL of 0.9% normal saline was administered intravenously. In the intravenous group, patients received ISB with 12 mL of 0.5% ropivacaine; simultaneously, 1 mL of dexamethasone 5 mg was administered intravenously. The primary outcome was the difference in the pain score (0-10 on numeric rating scale) between before and after ISB resolution. The secondary outcomes were the incidence of rebound pain; onset, duration, and intensity of rebound pain; time to the first analgesic request; and pain-related sleep disturbance.
RESULTS
A total of 71 patients were randomized to either perineural group (n = 36) or intravenous group (n = 35). After block resolution, pain scores increased significantly more in the perineural group (mean ± standard deviation, 4.9 ± 2.1) compared to the intravenous group (4.0 ± 1.7, = 0.043). The duration of ISB was more prolonged in the perineural group (median [interquartile range], 19.9 [17.2-23.1] hours) than the intravenous group (15.1 [13.7-15.9] hours, < 0.001). The incidence of rebound pain and pain-related sleep disturbance during the first postoperative week was significantly higher in the perineural group than in the intravenous group (rebound pain: 44.4% vs. 20.0%, = 0.028; sleep disturbance: 55.6% vs. 25.7%, = 0.011). The duration and intensity of rebound pain were similar between the two groups.
CONCLUSION
Although perineural dexamethasone provided longer postoperative analgesia, intravenous dexamethasone was more beneficial in reducing pain increase after ISB resolution, incidence of rebound pain, and pain-related sleep disturbance.
TRIAL REGISTRATION
Clinical Research Information Service Identifier: KCT0006795.
Topics: Humans; Brachial Plexus Block; Ropivacaine; Anesthetics, Local; Rotator Cuff Injuries; Pain, Postoperative; Arthroscopy; Dexamethasone
PubMed: 37337808
DOI: 10.3346/jkms.2023.38.e183 -
The Eurasian Journal of Medicine Jun 2020Spinal hematoma following neuraxial or perineural techniques is a rare but severe complication that can potentially lead to catastrophic consequences. The aim of this... (Review)
Review
Spinal hematoma following neuraxial or perineural techniques is a rare but severe complication that can potentially lead to catastrophic consequences. The aim of this review is to analyze all reported cases of neuraxial or perineural bleeding after performance of a locoregional technique since the last guidelines update in 2018. We included articles indexed by MEDLINE, Scopus, and Google Scholar. We analyzed the patient's age, surgical procedure, pre-operative anticoagulant and antiplatelet therapy, type of anesthetic procedure, vertebra level of the procedure, diameter and point type of the needle, hematoma type (spinal, subdural, epidural), signs and symptoms, time to imaging, and time to treatment and outcome. During our bibliographic research, we identified 5637 unique articles that were eligible according to our protocol criteria, identifying 18 separate cases of neuraxial bleeding. Although clinicians are usually aware of antiplatelet and anticoagulant perioperative management, a careful post-procedural observation and a detailed patient education are also imperative for the early detection of the symptoms of spinal cord ischemia.
PubMed: 32612433
DOI: 10.5152/eurasianjmed.2019.19212 -
Journal of Neurological Surgery. Part... Apr 2016Head and neck malignancies with orbital involvement present difficult decisions to the treating physician. When the spread is perineural, the challenges are greater due... (Review)
Review
Head and neck malignancies with orbital involvement present difficult decisions to the treating physician. When the spread is perineural, the challenges are greater due to the incipient nature of the spread and the fact that the orbit can also be involved by centrifugal spread from the non-ophthalmic branches of the trigeminal nerve. The disease is often misdiagnosed and the subsequent delay in treatment results in worse outcomes. This article discusses the evaluation of the eye and the many facets of orbital involvement by perineural spread of malignancy including the treatment of complications.
PubMed: 27123389
DOI: 10.1055/s-0036-1582239 -
Frontiers in Neuroanatomy 2023Neuropathic pain arises from damage or disorders affecting the somatosensory system. In rats, L5 nerve injury induces thermal and mechanical...
Neuropathic pain arises from damage or disorders affecting the somatosensory system. In rats, L5 nerve injury induces thermal and mechanical hypersensitivity/hyperalgesia. Recently, we demonstrated that applying resiniferatoxin (RTX) directly on uninjured L3 and L4 nerves alleviated thermal and mechanical hypersensitivity resulting from L5 nerve injury. Herein, using immunohistochemistry, Western blot, and qRT-PCR techniques, we reveal that perineural application of RTX (0.002%) on the L4 nerve substantially downregulated the expression of its receptor (Trpv1) and three different voltage-gated ion channels (Nav1.9, Kv4.3, and Cav2.2). These channels are found primarily in small-sized neurons and show significant colocalization with Trpv1 in the dorsal root ganglion (DRG). However, RTX treatment did not affect the expression of Kv1.1, Piezo2 (found in large-sized neurons without colocalization with Trpv1), and Kir4.1 (localized in satellite cells) in the ipsilateral DRGs. Furthermore, RTX application on L3 and L4 nerves reduced the activation of c-fos in the spinal neurons induced by heat stimulation. Subsequently, we investigated whether applying RTX to the L3 and L4 nerves 3 weeks before the L5 nerve injury could prevent the onset of neuropathic pain. Both 0.002 and 0.004% concentrations of RTX produced significant analgesic effects, while complete prevention of thermal and mechanical hypersensitivity required a concentration of 0.008%. Importantly, this preventive effect on neuropathic manifestations was not associated with nerve degeneration, as microscopic examination revealed no morphological changes. Overall, this study underscores the mechanisms and the significance of perineural RTX treatment applied to adjacent uninjured nerves in entirely preventing nerve injury-induced neuropathic pain in humans and animals.
PubMed: 38099210
DOI: 10.3389/fnana.2023.1306180 -
Cells Apr 2023Tertiary lymphoid structures (TLSs) mediate local antitumor immunity, and interest in them significantly increased since cancer immunotherapy was implemented. We...
Tertiary Lymphoid Structures (TLSs) and Stromal Blood Vessels Have Significant and Heterogeneous Impact on Recurrence, Lymphovascular and Perineural Invasion amongst Breast Cancer Molecular Subtypes.
BACKGROUND
Tertiary lymphoid structures (TLSs) mediate local antitumor immunity, and interest in them significantly increased since cancer immunotherapy was implemented. We examined TLS- tumor stromal blood vessel interplay for each breast cancer (BC) molecular subtype related to recurrence, lymphovascular invasion (LVI), and perineural invasion (PnI).
METHODS
TLSs were quantified on hematoxylin and eosin stain specimens followed by CD34/smooth muscle actin (SMA) double immunostaining for stromal blood vessel maturation assessment. Statistical analysis linked microscopy to recurrence, LVI, and PnI.
RESULTS
TLS negative (TLS-) subgroups in each BC molecular subtype (except to Luminal A) have higher LVI, PnI, and recurrence. A significant rise in LVI and PnI were observed for the HER2+/TLS- subgroup ( < 0.001). The triple negative breast cancer (TNBC)/TLS- subgroup had the highest recurrence and invasion risk which was also significantly related to tumor grade. PnI but not LVI significantly influenced recurrence in the TNBC/TLS+ subgroup ( < 0.001). TLS-stromal blood vessel interrelation was different amongst BC molecular subtypes.
CONCLUSION
BC invasion and recurrence are strongly influenced by TLS presence and stromal blood vessels, especially for HER2 and TNBC BC molecular subtypes.
Topics: Humans; Triple Negative Breast Neoplasms; Tertiary Lymphoid Structures; Neoplasm Invasiveness; Breast
PubMed: 37190085
DOI: 10.3390/cells12081176