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Clinical Cancer Research : An Official... Aug 2017Large diameter perineural prostate cancer is associated with poor outcomes. GDNF, with its coreceptor GFRα1, binds RET and activates downstream pro-oncogenic...
Large diameter perineural prostate cancer is associated with poor outcomes. GDNF, with its coreceptor GFRα1, binds RET and activates downstream pro-oncogenic signaling. Because both GDNF and GFRα1 are secreted by nerves, we examined the role of RET signaling in prostate cancer. Expression of RET, GDNF, and/or GFRα1 was assessed. The impact of RET signaling on proliferation, invasion and soft agar colony formation, perineural invasion, and growth was determined. Cellular signaling downstream of RET was examined by Western blotting. RET is expressed in all prostate cancer cell lines. GFRα1 is only expressed in 22Rv1 cells, which is the only line that responds to exogenous GDNF. In contrast, all cell lines respond to GDNF plus GFRα1. Conditioned medium from dorsal root ganglia contains secreted GFRα1 and promotes transformation-related phenotypes, which can be blocked by anti-GFRα1 antibody. Perineural invasion in the dorsal root ganglion assay is inhibited by anti-GFRα antibody and RET knockdown. , knockdown of RET inhibits tumor growth. RET signaling activates ERK or AKT signaling depending on context, but phosphorylation of p70S6 kinase is markedly increased in all cases. Knockdown of p70S6 kinase markedly decreases RET induced transformed phenotypes. Finally, RET is expressed in 18% of adenocarcinomas and all three small-cell carcinomas examined. RET promotes transformation associated phenotypes, including perineural invasion in prostate cancer via activation of p70S6 kinase. GFRα1, which is secreted by nerves, is a limiting factor for RET signaling, creating a perineural niche where RET signaling can occur. .
Topics: Animals; Cell Line; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; HEK293 Cells; Humans; Male; Mice, Inbred C57BL; Mice, SCID; Prostatic Neoplasms; Proto-Oncogene Proteins c-ret; RNA Interference; RNAi Therapeutics; Signal Transduction; Tumor Burden; Xenograft Model Antitumor Assays
PubMed: 28490466
DOI: 10.1158/1078-0432.CCR-17-0528 -
Journal of Orthopaedic Surgery and... Feb 2022The analgesic comparison between perineural and intravenous dexamethasone on interscalene block for pain management after shoulder arthroscopy remains controversial. We... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The analgesic comparison between perineural and intravenous dexamethasone on interscalene block for pain management after shoulder arthroscopy remains controversial. We conduct this meta-analysis to explore the influence of perineural versus intravenous dexamethasone on interscalene block for pain control after shoulder arthroscopy.
METHODS
We have searched PubMed, Embase, Web of science, EBSCO and Cochrane library databases through April 2021 and included randomized controlled trials (RCTs) assessing the effect of perineural and intravenous dexamethasone on interscalene block in patients with shoulder arthroscopy.
RESULTS
Five RCTs were included in the meta-analysis. Overall, compared with intravenous dexamethasone for shoulder arthroscopy, perineural dexamethasone led to similar block duration (SMD = 0.12; 95% CI - 0.12 to 0.35; P = 0.33), pain scores at 12 h (SMD = - 0.67; 95% CI - 1.48 to 0.15; P = 0.11), pain scores at 24 h (SMD = - 0.33; 95% CI - 0.79 to 0.14; P = 0.17), opioid consumption (SMD = 0.01; 95% CI - 0.18 to 0.19; P = 0.95) and incidence of nausea/vomiting (OR = 0.74; 95% CI 0.38-1.44; P = 0.38).
CONCLUSIONS
Perineural and intravenous dexamethasone demonstrated comparable pain relief after shoulder arthroscopy.
Topics: Administration, Intravenous; Analgesics; Arthroscopy; Dexamethasone; Humans; Pain Management; Pain, Postoperative; Randomized Controlled Trials as Topic; Shoulder
PubMed: 35177116
DOI: 10.1186/s13018-022-02952-6 -
Cancers Nov 2021The most common oral cavity cancer is squamous cell carcinoma (SCC), of which perineural invasion (PNI) is a significant prognostic factor associated with decreased... (Review)
Review
The most common oral cavity cancer is squamous cell carcinoma (SCC), of which perineural invasion (PNI) is a significant prognostic factor associated with decreased survival and an increased rate of locoregional recurrence. In the classical theory of PNI, cancer was believed to invade nerves directly through the path of least resistance in the perineural space; however, more recent evidence suggests that PNI requires reciprocal signaling interactions between tumor cells and nerve components, particularly Schwann cells. Specifically, head and neck SCC can express neurotrophins and neurotrophin receptors that may contribute to cancer migration towards nerves, PNI, and neuritogenesis towards cancer. Through reciprocal signaling, recent studies also suggest that Schwann cells may play an important role in promoting PNI by migrating toward cancer cells, intercalating, and dispersing cancer, and facilitating cancer migration toward nerves. The interactions of neurotrophins with their high affinity receptors is a new area of interest in the development of pharmaceutical therapies for many types of cancer. In this comprehensive review, we discuss diagnosis and treatment of oral cavity SCC, how PNI affects locoregional recurrence and survival, and the impact of adjuvant therapies on tumors with PNI. We also describe the molecular and cellular mechanisms associated with PNI, including the expression of neurotrophins and their receptors, and highlight potential targets for therapeutic intervention for PNI in oral SCC.
PubMed: 34885121
DOI: 10.3390/cancers13236011 -
PeerJ 2022Lymphangio vascular invasion (LVI) and perineural invasion (PNI) are associated with survival following resection for gastrointestinal cancer. But the relationship...
Influence of Lymphangio vascular (V) and perineural (N) invasion on survival of patients with resected esophageal squamous cell carcinoma (ESCC): a single-center retrospective study.
BACKGROUND
Lymphangio vascular invasion (LVI) and perineural invasion (PNI) are associated with survival following resection for gastrointestinal cancer. But the relationship between LVI/PNI and survival of esophageal squamous cell carcinoma (ESCC) is still unclear. We aim to demonstrate the prognostic significance of LVI/PNI in ESCC.
METHODS
A total of 195 ESCC patients underwent curative surgery from 2012 to 2018 was collected in the 2nd Affiliated Hospital of Fujian Medical University. All the patients were divided into four groups based on the status of the neurovascular invasion: (1) neither LVI nor PNI (V0N0); (2) LVI alone (V1N0); (3) PNI alone (V0N1); (4) combined LVI and PNI (V1N1). First, the analysis included the Kaplan-Meier survival estimates with the Log rank test were performed to determine median overall survival (OS) in different groups divided according to the clinical factor, respectively. And the association between OS with multi clinical factors was examined using Cox regression analysis. Next, the risk factors for recurrence in patients with V1N1 were analyzed with univariate and multivariate logistic regression analyses, respectively.
RESULTS
The cases in V0N0, V1N0, V0N1, and V1N1 groups were 91 (46.7%), 62 (31.8%), 9 (4.6%) and 33 (16.9%), respectively. The OS in the four groups was different ( < 0.001). The 1-, 3- and 5-year OS in V0N0 group was higher than that in V1N1 group, respectively (1-year OS: 93.4% 75.8%, 3-year OS: 53.8 % 24.2%, 5-year OS: 48.1% 10.5%). The OS in stage I-II for patients with V1N1 was significantly lower than that in the other groups (V0N0, V1N0, V0N1) ( < 0.001). The postoperative adjuvant chemotherapy was a significant impact factor of OS for ESCC patients with V1N1 ( = 0.004). Lymphatic invasion and LVI were significantly prognosis factors associated ( = 0.036, = 0.030, respectively). The ulcerative type is a risk factor for V1N1 occurance ( = 0.040).
CONCLUSIONS
The LVI and PNI are important prognosis factors for ESCC patients. ESCC patients with simultaneous lymphangio vascular and perineural invasion (V1N1) showed worse OS than patients with either lymphangio vascular or perineural invasion alone (V1N0 or V0N1) or none (V0N0). In addition, adjuvant chemotherapy may prolong the OS for ESCC patients with V1N1.
Topics: Humans; Esophageal Squamous Cell Carcinoma; Retrospective Studies; Esophageal Neoplasms; Carcinoma, Squamous Cell; Disease-Free Survival
PubMed: 35256918
DOI: 10.7717/peerj.12974 -
Cancer Jan 2007Men with clinically localized prostate cancer are faced with a wide range of treatment options, and only Gleason grading is universally used as a histopathological... (Review)
Review
Men with clinically localized prostate cancer are faced with a wide range of treatment options, and only Gleason grading is universally used as a histopathological prognostic factor for this disease. The significance of perineural invasion in diagnostic biopsies is controversial. Opinion about whether or not it should influence treatment decisions is currently almost equally divided. To address this, the authors performed a systematic review of studies that examine the association between perineural invasion and prostate cancer recurrence. MEDLINE, Embase, and the Web of Knowledge were searched from January 1990 to December 2005. Outcomes analyzed were the development of biochemical or clinical recurrence. Twenty-one articles on the association of perineural invasion in biopsies and prostate cancer recurrence after radical prostatectomy (n = 10) or radiotherapy (n = 11) were found but none on its significance in the context of watchful waiting. Structured data extraction was performed to allow comparisons between articles and to identify sources of heterogeneity to explain discrepancies in results. The considerable variation in study design, execution, and reporting precluded meta-analysis and quantitative risk estimation, but the weight of evidence suggested that perineural invasion in biopsies was a significant prognostic indicator, particularly in specific patient groups defined by presenting serum prostate-specific antigen levels and biopsy Gleason scores. Immediate treatment rather than watchful waiting may be more appropriate for patients with localized prostatic cancer and perineural invasion. However, the data are limited, and well-designed studies that use predefined stringent protocols are required to provide robust estimates of risk to aid in treatment planning.
Topics: Adenocarcinoma; Adult; Aged; Biopsy; Humans; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Peripheral Nerves; Prognosis; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms
PubMed: 17123267
DOI: 10.1002/cncr.22388 -
Anesthesia, Essays and Researches 2021The effect of perineural versus intravenous (i.v.) dexamethasone (4 mg) when added to levobupivacaine as an adjuvant has not been well studied.
Comparison of Perineural and Intravenous Dexamethasone as an Adjuvant to Levobupivacaine in Ultrasound-Guided Infraclavicular Brachial Plexus Block: A prospective Randomized Trial.
BACKGROUND
The effect of perineural versus intravenous (i.v.) dexamethasone (4 mg) when added to levobupivacaine as an adjuvant has not been well studied.
AIMS
This study was conducted to compare the analgesic efficacy of perineural and i.v. dexamethasone as an adjuvant to levobupivacaine in infraclavicular brachial plexus (ICBP) block.
SETTINGS AND DESIGN
This was a prospective, randomized, double-blind study.
MATERIALS AND METHODS
This study was conducted on 68 patients with the ultrasound-guided ICBP block, randomly allocated into two groups (34 each). Four patients had failed block (2 in each group) that was excluded from the study. Group A received 25 mL of levobupivacaine 0.5% and 1 mL of normal saline for the block and i.v. dexamethasone 4 mg. Group B received 25 mL of levobupivacaine 0.5% with 4 mg of perineural dexamethasone for the block. Postoperative vitals and different block characteristics were assessed.
STATISTICAL ANALYSIS USED
Student's independent sample -test and Chi-square test were used for statistical analysis.
RESULTS
The duration of motor block and analgesia in Group A was 1245.94 ± 153.22 min and 1310.16 ± 151.68 min, respectively. However, in Group B, the duration of motor block and analgesia was 1768.13 ± 309.86 min and 1743.59 ± 231.39 min, respectively, which was more when compared to Group A ( < 0.001). The Visual Analog Scale score of ≥3 in Group A was 37% and in Group B was 9% ( = 0.008). Four cases had delayed regression of motor block in the perineural group.
CONCLUSIONS
Perineural dexamethasone significantly prolonged the duration of motor block promoted by levobupivacaine in infraclavicular brachial plexus block, reduced pain intensity and rescue analgesia needs in the postoperative period when compared with the intravenous dexamethasone.
PubMed: 34667347
DOI: 10.4103/aer.aer_69_21 -
Pancreatology : Official Journal of the... Jun 2024Perineural invasion (PNI), classified according to its presence or absence in tumor specimens, is recognized as a poor prognostic factor in pancreatic ductal...
BACKGROUND/OBJECTIVES
Perineural invasion (PNI), classified according to its presence or absence in tumor specimens, is recognized as a poor prognostic factor in pancreatic ductal adenocarcinoma (PDAC) patients. Herein, we identified five histological features of PNI and investigated their impact on survival outcomes of PDAC resected patients.
METHODS
Five histopathological features of PNI (diameter, number, site, sheath involvement, and mitotic figures within perineural invasion) were combined in an additional final score (ranging from 0 to 8), and clinical data of PDAC patients were retrospectively analyzed. PNI + patients were stratified in two categories according to the median score value (<6 and ≥ 6, respectively). Impact of PNI on disease-free survival (DFS) and overall survival (OS) were analyzed.
RESULTS
Forty-five patients were enrolled, of whom 34 with PNI (PNI+) and 11 without PNI (PNI-). The DFS was 11 months vs. not reached (NR) (p = 0.258), while the OS was 19 months vs. NR (p = 0.040) in PNI+ and PNI- patients, respectively. A ≥6 PNI was identified as an independent predictor of worse OS vs. <6 PNI + patients (29 vs. 11 months, p < 0.001) and <6 PNI+ and PNI- patients (43 vs. 11 months, p < 0.001). PNI ≥6 was an independent negative prognostic factor of DFS vs. <6 PNI+ and PNI- patients (13 vs. 6 months, p = 0.022).
CONCLUSIONS
We report a PNI scoring system that stratifies surgically-treated PDAC patients in a graded manner that correlates with patient prognosis better than the current dichotomous (presence/absence) definition. However, further and larger studies are needed to support this PNI scoring system.
Topics: Humans; Pancreatic Neoplasms; Male; Female; Aged; Middle Aged; Neoplasm Invasiveness; Retrospective Studies; Carcinoma, Pancreatic Ductal; Prognosis; Disease-Free Survival; Treatment Outcome; Aged, 80 and over; Peripheral Nerves; Adult; Survival Analysis
PubMed: 38514359
DOI: 10.1016/j.pan.2024.03.004 -
British Journal of Anaesthesia Jun 2013Nerve blocks improve postoperative analgesia, but their benefits may be short-lived. This quantitative review examines whether perineural dexmedetomidine as a local... (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
Nerve blocks improve postoperative analgesia, but their benefits may be short-lived. This quantitative review examines whether perineural dexmedetomidine as a local anaesthetic (LA) adjuvant for neuraxial and peripheral nerve blocks can prolong the duration of analgesia compared with LA alone. All randomized controlled trials (RCTs) comparing the effect of dexmedetomidine as an LA adjuvant to LA alone on neuraxial and peripheral nerve blocks were reviewed. Sensory block duration, motor block duration, block onset times, analgesic consumption, time to first analgesic request, and side-effects were analysed.
RESULTS
were combined using random-effects modelling. A total of 516 patients were analysed from nine RCTs. Five trials investigated dexmedetomidine as part of spinal anaesthesia and four as part of a brachial plexus (BP) block. Sensory block duration was prolonged by 150 min [95% confidence interval (CI): 96, 205, P<0.00001] with intrathecal dexmedetomidine. Perineural dexmedetomidine used in BP block may prolong the mean duration of sensory block by 284 min (95% CI: 1, 566, P=0.05), but this difference did not reach statistical significance. Motor block duration and time to first analgesic request were prolonged for both intrathecal and BP block. Dexmedetomidine produced reversible bradycardia in 7% of BP block patients, but no effect on the incidence of hypotension. No patients experienced respiratory depression. Dexmedetomidine is a potential LA adjuvant that can exhibit a facilitatory effect when administered intrathecally as part of spinal anaesthesia or peripherally as part of a BP block. However, there are presently insufficient safety data to support perineural dexmedetomidine use in the clinical setting.
Topics: Adjuvants, Anesthesia; Adrenergic alpha-2 Receptor Agonists; Anesthetics, Local; Brachial Plexus; Dexmedetomidine; Humans; Nerve Block
PubMed: 23587874
DOI: 10.1093/bja/aet066 -
Thoracic Cancer May 2021Although perineural invasion is a well known prognostic factor used in several cancers, its prognostic role in esophageal squamous cell carcinoma remains controversial....
BACKGROUND
Although perineural invasion is a well known prognostic factor used in several cancers, its prognostic role in esophageal squamous cell carcinoma remains controversial. Here, we investigated the prognostic role of perineural invasion in surgically treated esophageal squamous cell carcinoma.
METHODS
We retrospectively reviewed the medical records of 316 patients who underwent esophagectomy and lymph node dissection for esophageal squamous cell carcinoma between 2007 and 2016.
RESULTS
Overall, 287 men (mean age: 62.73 ± 7.97 years) were included in the study. The median follow-up period was 35.97 ± 30.99 months, perineural invasion was confirmed in 25 patients, and three-year overall and disease-free survival were significantly lower in the perineural invasion group than in the no-perineural invasion group (75.9% vs. 40.0%, p < 0.001; 70.3% vs. 21.6%, p < 0.001). Cumulative incidences of locoregional recurrence and distant metastasis over three years were higher in the perineural invasion group (13.8% vs. 9.6%, p = 0.009 and 52.8% vs. 14.6%, p < 0.001). On performing multivariable analysis, perineural invasion, pathological stage, incomplete resection, and neoadjuvant therapy were adverse risk factors for disease-free survival. The concordance index increased when perineural invasion was included in the model (0.712 vs. 0.723). On subgroup analysis, perineural invasion demonstrated a prognostic value in node-negative patients (79.4% vs. 35.7%, p = 0.012).
CONCLUSIONS
Perineural invasion was found to be an adverse risk factor for disease-free survival in surgically treated patients with esophageal squamous cell carcinoma. Close observation and individualized adjuvant therapy may be helpful for patients with perineural invasion.
Topics: Esophageal Squamous Cell Carcinoma; Female; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Prognosis; Retrospective Studies; Risk Factors
PubMed: 33811752
DOI: 10.1111/1759-7714.13960 -
BMC Gastroenterology Sep 2023Pancreatic cancer is a fatal tumor, and the status of perineural invasion (PNI) of pancreatic cancer was positively related to poor prognosis including overall survival...
BACKGROUND
Pancreatic cancer is a fatal tumor, and the status of perineural invasion (PNI) of pancreatic cancer was positively related to poor prognosis including overall survival and recurrence-free survival. This study aims to develop and validate a predictive model based on serum biomarkers to accurately predict the perineural invasion.
MATERIALS AND METHODS
The patients from No.924 Hospital of PLA Joint Logistic Support Force were included. The predictive model was developed in the training cohort using logistic regression analysis, and then tested in the validation cohort. The area under curve (AUC), calibration curves and decision curve analysis were used to validate the predictive accuracy and clinical benefits of nomogram.
RESULTS
A nomogram was developed using preoperative total bilirubin, preoperative blood glucose, preoperative CA19-9. It achieved good AUC values of 0.753 and 0.737 in predicting PNI in training and validation cohorts, respectively. Calibration curves showed nomogram had good uniformity of the practical probability of PNI. Decision curve analyses revealed that the nomogram provided higher diagnostic accuracy and superior net benefit compared to single indicators.
CONCLUSION
The present study constructed and validate a novel nomogram predicted the PNI of resectable PHAC patients with high stability and accuracy. Besides, it could better screen high-risk probability of PNI in these patients, and optimize treatment decision-making.
Topics: Humans; Nomograms; Pancreatic Neoplasms; Area Under Curve; CA-19-9 Antigen
PubMed: 37723476
DOI: 10.1186/s12876-023-02819-y