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Journal of Clinical Medicine May 2021(1) Background: Intrahepatic cholangiocarcinoma (ICC) is a rare malignancy. Besides tumor, nodal, and metastatic status, the UICC TNM classification describes further...
(1) Background: Intrahepatic cholangiocarcinoma (ICC) is a rare malignancy. Besides tumor, nodal, and metastatic status, the UICC TNM classification describes further parameters such as lymphangio- (L0/L1), vascular (V0/V1/V2), and perineural invasion (Pn0/Pn1). The aim of this study was to analyze the influence of these parameters on recurrence and survival. (2) Methods: All surgical explorations for patients with ICC between January 2008 and June 2018 were collected and further analyzed in our institutional database. Statistical analyses focused on perineural, lymphangio-, and vascular invasion examined histologically and their influence on tumor recurrence and survival. (3) Results: Of 210 patients who underwent surgical exploration, 150 underwent curative-intended resection. Perineural invasion was present in 41, lymphangioinvasion in 21, and vascular invasion in 37 patients (V1 = 34, V2 = 3). Presence of P1, V+ and L1 was significantly associated with positivity of each other of these factors ( < 0.001, each). None of the three parameters showed direct influence on tumor recurrence in general, but perineural invasion influenced extrahepatic recurrence significantly ( = 0.019). Whereas lymphangio and vascular invasion was neither associated with overall nor recurrence-free survival, perineural invasion was significantly associated with a poor 1-, 3- and 5-year overall survival (OS) of 80%, 35%, and 23% for Pn0 versus 75%, 23%, and 0% for Pn1 ( = 0.027). Concerning recurrence-free survival (RFS), Pn0 showed a 1-, 3- and 5-year RFS of 42%, 18%, and 16% versus 28%, 11%, and 0% for Pn1, but no significance was reached ( = 0.091). (4) Conclusions: Whereas lymphangio- and vascular invasion showed no significant influence in several analyses, the presence of perineural invasion was associated with a significantly higher risk of extrahepatic tumor recurrence and worse overall survival.
PubMed: 34070745
DOI: 10.3390/jcm10112426 -
International Journal of General... 2023Colon cancer is a prevalent gastrointestinal malignancy that often exhibits distant metastasis, hindering the effectiveness of surgical interventions. In addition to...
BACKGROUND
Colon cancer is a prevalent gastrointestinal malignancy that often exhibits distant metastasis, hindering the effectiveness of surgical interventions. In addition to well-known hematogenous and lymphatic metastasis, perineural invasion (PNI) has emerged as a significant mode of distant metastasis in colon tumors. PNI is closely associated with oncologic pain in advanced cancer patients, but the underlying mechanisms and associated biomarkers, which might be the novel therapeutic targets, remain poorly understood.
METHODS
In this study, we employed large databases and bioinformatics methods to identify genes strongly linked to PNI in colon cancer and investigated their involvement in tumor nerve invasion, progression mechanisms, and chemotherapy resistance. Immunohistochemical techniques were utilized to validate the expression of target genes in 384 colon cancer tissues, and their expression was correlated with clinicopathological characteristics and patient survival data in our hospital. Furthermore, we conducted a comprehensive literature review to explore the potential functions of the target genes and their associated genes.
RESULTS
Our screening revealed a significant correlation between neural proliferation differentiation and control-1 (NPDC1) expression and patient prognosis, suggesting a potential association with neural infiltration in colon cancer. Additionally, NPDC1 may promote tumorigenesis, progression, and chemoresistance through various related pathways.
CONCLUSION
Our study provides novel insights into the utility of NPDC1 as a predictive marker for PNI status, disease-free survival, and overall survival in patients with colon cancer, highlighting the prevalence of NPDC1 overexpression in patients with PNI in colon cancer.
PubMed: 37822345
DOI: 10.2147/IJGM.S428590 -
Insights Into Imaging Aug 2016The pterygopalatine fossa (PPF) is a small, clinically inaccessible, fat-filled space located in the deep face that serves as a major neurovascular crossroad between the... (Review)
Review
UNLABELLED
The pterygopalatine fossa (PPF) is a small, clinically inaccessible, fat-filled space located in the deep face that serves as a major neurovascular crossroad between the oral cavity, nasal cavity, nasopharynx, orbit, masticator space, and the middle cranial fossa. Due to its inherent complex location and connections, it can potentially act as a natural conduit for the spread of inflammatory and neoplastic diseases across the various deep spaces in the head and neck. This review aims to acquaint the reader with the imaging anatomy of the PPF, its important communications, and to identify some major pathological conditions that can involve the PPF, especially in conditions where its involvement can have serious diagnostic and therapeutic implications, such as in perineural tumour spread.
TEACHING POINTS
• The PPF is a small neurovascular junction in the deep face with important to-and-fro connections. • Awareness of anatomy of the PPF and its communications helps to simplify imaging of its pathology. • Perineural tumour spread is clinically the most important pathology in this region.
PubMed: 27230518
DOI: 10.1007/s13244-016-0498-1 -
Journal of Maxillofacial and Oral... Jun 2022Head and neck cancer represents 5-10% of all malignancies. Squamous cell carcinoma (SCC) of the oral cavity represents about 2% of overall malignant neoplasms and 47% of...
The Interrelation Among Triad of Depth of Invasion, Perineural Invasion and Tumor Size in Squamous Cell Carcinoma of Tongue and Floor of the Mouth: An Analytical Appraisal.
BACKGROUND
Head and neck cancer represents 5-10% of all malignancies. Squamous cell carcinoma (SCC) of the oral cavity represents about 2% of overall malignant neoplasms and 47% of the head and neck region Squamous cell carcinoma of tongue has a peculiar behavior of occult and skips metastasis to regional lymph nodes. It occasionally occurs along with floor of the mouth. The purpose of this study is to evaluate the significance of correlation between, depth of invasion of the primary tumor, its proximity with the neurovascular bundle and subsequent perineural invasion and cervical lymph node metastasis in squamous cell carcinoma tongue and floor of the mouth and the sites involving both.
MATERIALS AND METHODS
A total of 108 patients with carcinoma tongue (59), floor of the mouth (20) and involving both together (29) who underwent treatment during January 2015 to June 2017 that were followed up until December 2019 were assessed. Out of 108 patients that were included in the study, 71 patients underwent primary surgery and 37 patients were inoperable (tongue-17, floor of the mouth-9 and involving both together-11).
RESULTS
Perineural invasion was seen in 15 cases of pT1-2 where depth of invasion was less than 1 cm and in 28 cases of pT3-4 where depth of invasion was more than 1cm (-0.075). Skip metastasis was accounted for 61.9% overall.
CONCLUSION
The triad of perineural invasion, depth of invasion and tumor size is interrelated and was responsible for cervical lymph node metastasis and prognosis of the disease. Obtaining clear deep margins of the tumor from the mucosal margin and removal of lympho-fatty tissue at the floor of the mouth is an important aspect which gives the indication about prognostic factors like depth of invasion, tumor size, cervical nodal metastasis and recurrence of the disease. High-grade tumors (T3-4), depth of invasion of tumor at 1 cm or > 1 cm, increase the propensity of perineural invasion highly.
PubMed: 35712423
DOI: 10.1007/s12663-022-01685-7 -
Cancers Nov 2022Pancreatic ductal adenocarcinoma is one of the most threatening solid malignancies. Molecular and cellular mediators that activate paracrine signalling also regulate the... (Review)
Review
Pancreatic ductal adenocarcinoma is one of the most threatening solid malignancies. Molecular and cellular mediators that activate paracrine signalling also regulate the dynamic interaction between pancreatic cancer cells and nerves. This reciprocal interface leads to perineural invasion (PNI), defined as the ability of cancer cells to invade nerves, similar to vascular and lymphatic metastatic cascade. Targeting PNI in pancreatic cancer might help ameliorate prognosis and pain relief. In this review, the modern knowledge of PNI in pancreatic cancer has been analysed and critically presented. We focused on molecular pathways promoting cancer progression, with particular emphasis on neuropathic pain generation, and we reviewed the current knowledge of pharmacological inhibitors of the PNI axis. PNI represents a common hallmark of PDAC and correlates with recurrence, poor prognosis and pain in pancreatic cancer patients. The interaction among pancreatic cancer cells, immune cells and nerves is biologically relevant in each stage of the disease and stimulates great interest, but the real impact of the administration of novel agents in clinical practice is limited. It is still early days for PNI-targeted treatments, and further advanced studies are needed to understand whether they could be effective tools in the clinical setting.
PubMed: 36497277
DOI: 10.3390/cancers14235793 -
American Journal of Veterinary Research Jun 2021To evaluate the effects of using ropivacaine combined with dexmedetomidine for sciatic and saphenous nerve blocks in dogs.
Effects of perineural administration of ropivacaine combined with perineural or intravenous administration of dexmedetomidine for sciatic and saphenous nerve blocks in dogs.
OBJECTIVE
To evaluate the effects of using ropivacaine combined with dexmedetomidine for sciatic and saphenous nerve blocks in dogs.
ANIMALS
7 healthy adult Beagles.
PROCEDURES
In phase 1, dogs received each of the following 3 treatments in random order: perineural sciatic and saphenous nerve injections of 0.5% ropivacaine (0.4 mL/kg) mixed with saline (0.9% NaCl) solution (0.04 mL/kg; DEX0PN), 0.5% ropivacaine mixed with dexmedetomidine (1 μg/kg; DEX1PN), and 0.5% ropivacaine mixed with dexmedetomidine (2 μg/kg; DEX2PN). In phase 2, dogs received perineural sciatic and saphenous nerve injections of 0.5% ropivacaine and an IV injection of diluted dexmedetomidine (1 μg/kg; DEX1IV). For perineural injections, the dose was divided equally between the 2 sites. Duration of sensory blockade was evaluated, and plasma dexmedetomidine concentrations were measured.
RESULTS
Duration of sensory blockade was significantly longer with DEX1PN and DEX2PN, compared with DEX0PN; DEX1IV did not prolong duration of sensory blockade, compared with DEX0PN. Peak plasma dexmedetomidine concentrations were reached after 15 minutes with DEX1PN (mean ± SD, 348 ± 200 pg/mL) and after 30 minutes DEX2PN (816 ± 607 pg/mL), and bioavailability was 54 ± 40% and 73 ± 43%, respectively. The highest plasma dexmedetomidine concentration was measured with DEX1IV (1,032 ± 415 pg/mL) 5 minutes after injection.
CONCLUSIONS AND CLINICAL RELEVANCE
Results suggested that perineural injection of 0.5% ropivacaine in combination with dexmedetomidine (1 μg/kg) for locoregional anesthesia in dogs seemed to balance the benefit of prolonging sensory nerve blockade while minimizing adverse effects.
Topics: Administration, Intravenous; Anesthetics, Local; Animals; Dexmedetomidine; Dogs; Nerve Block; Ropivacaine; Sciatic Nerve
PubMed: 34032477
DOI: 10.2460/ajvr.82.6.449 -
Cancer Diagnosis & Prognosis 2022Some prognostic factors for pancreatic neuroendocrine neoplasms (PanNENs) have been reported; however, the significance of lymphatic, microvascular, and perineural...
BACKGROUND
Some prognostic factors for pancreatic neuroendocrine neoplasms (PanNENs) have been reported; however, the significance of lymphatic, microvascular, and perineural invasion remains unclear. We aimed to clarify the role of these factors in PanNEN recurrence.
PATIENTS AND METHODS
We analyzed 138 patients who underwent curative pancreatectomy and were pathologically diagnosed with PanNEN. We evaluated the association between clinicopathological factors and the recurrence of PanNENs.
RESULTS
The numbers of patients with lymphatic, microvascular, and perineural invasion were 34 (25%), 43 (31%) and 17 (12%), respectively. Twenty-four patients (17%) had recurrences, and the 3, 5, and 10-year recurrence-free survival (RFS) rates were 88%, 84%, and 76%, respectively. The recurrence sites (with duplication) were mainly the liver (twenty-two patients), followed by the lymph nodes (seven patients), and bone (two patients). In multivariate analyses, grade 2-3 and the presence of microvascular invasion were significant risk factors for RFS (hazard ratio=7.5 and 7.9, respectively). When examining outcomes according to these factors, the 5-year RFS rates of patients with risk scores of 0, 1, and 2 were 100%, 91%, and 32%, respectively (p<0.001). Even in patients with grade 1 (n=97) or limited resection (enucleation, splenic-preserving distal pancreatectomy, central pancreatectomy, and duodenum-preserving pancreatic head resection, n=62), the presence of microvascular invasion was a significant risk factor for RFS (hazard ratio=13.4 and 18.0, respectively).
CONCLUSION
The presence of microvascular invasion is an independent risk factor for recurrence in patients with PanNEN.
PubMed: 35399168
DOI: 10.21873/cdp.10089 -
Head and Neck Pathology Jun 2023Perineural invasion (PNI) is recognized as a poor prognostic factor in oral squamous cell carcinoma (OSCC). However, the prognostic significance of further...
BACKGROUND
Perineural invasion (PNI) is recognized as a poor prognostic factor in oral squamous cell carcinoma (OSCC). However, the prognostic significance of further histologic subcategorization of PNI is inconclusive. In this study, we determined the prognostic relevance of histologic subcategories of PNI and their correlation with the presence of other clinical and pathological parameters METHODS: This is a retrospective study of 207 homogeneously treated OSCC patients with histologically documented PNI from a single center. Univariate and multivariate survival outcomes, namely, local recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS) of patients with various subcategories of PNI,namely- number of foci, size of the involved nerve, extratumoral or intratumoral extent, and intraneural or perineural location-were determined.
RESULTS
Within the histologic subcategories of PNI, tongue primary and presence of lymph node metastasis correlated significantly with the number of nerves involved with PNI. Larger size of involved nerve correlated with advanced tumor stage. Number of foci, extent, and location of PNI were not prognostically significant except size of the involved nerve which showed an inverse correlation with disease outcome as involvement of larger nerves displayed better outcomes in terms of DFS and LRFS but not of OS on multivariate analysis. Addition of adjuvant chemotherapy to radiotherapy emerged as a significant predictor of improved LRFS, DFS, and OS.
CONCLUSIONS
Histologic subcategorization of PNI did not have prognostic relevance in our study. Involvement of even small nerves was associated with poor prognosis. Addition of chemoradiation was seen to improve prognosis.
Topics: Humans; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Mouth Neoplasms; Retrospective Studies; Prognosis; Head and Neck Neoplasms; Neoplasm Invasiveness; Neoplasm Staging; Peripheral Nerves
PubMed: 36480091
DOI: 10.1007/s12105-022-01512-y -
Critical Reviews in Oncology/hematology Apr 2017Perineural invasion is a clear route for cancer cell spread however, the role of nerves in cancer progression is relatively unknown. Recent work would suggest that... (Review)
Review
Perineural invasion is a clear route for cancer cell spread however, the role of nerves in cancer progression is relatively unknown. Recent work would suggest that nerves can actively infiltrate the tumour microenvironment and stimulate cancer cell growth. Therefore, the aim of the present study was to systematically review the identification and associations of perineural invasion and survival in patients with primary operable colorectal cancer. From initial search results of 912 articles, 38 studies were selected. Using H&E stains; five studies including 1835 patients reported on survival stratified by perineural invasion in colon cancer with weighted average detection rates of 26%; eleven studies including 3837 patients reported on rectal cancer with weighted average detection rates of 25% and; sixteen studies including 9145 patients reported on survival stratified by perineural invasion in colorectal cancer with weighted average detection rates of 17%. Using special techniques (S100), six studies including 1458 patients reported on the identification of perineural invasion in colorectal cancer. In comparison to H&E staining alone, the use of immunohistochemistry with S100 increased the detection of perineural invasion to approximately 70%. However, those studies did not examine the relationship with outcomes, so further research is required to establish the clinical significance of perineural invasion detected by immunohistochemistry. In conclusion, perineural invasion deserves special attention for improved prognostic stratification in patients with colorectal cancer. Further work is required to standardise pathology assessment and reporting of perineural invasion, in particular its definition, use of special stains and routine inclusion in pathology practice. Reliable assessment is required for investigations into mechanisms of perineural invasion, its role tumour spread and prognostic value.
Topics: Colorectal Neoplasms; Humans; Male; Neoplasm Invasiveness; Peripheral Nerves; Prognosis
PubMed: 28325252
DOI: 10.1016/j.critrevonc.2017.02.005 -
Case Reports in Dermatological Medicine 2014Importance. Cutaneous and systemic plasmacytosis are rare conditions of unknown etiology with characteristic red-brown skin lesions and a mature polyclonal plasma cell...
Importance. Cutaneous and systemic plasmacytosis are rare conditions of unknown etiology with characteristic red-brown skin lesions and a mature polyclonal plasma cell infiltrate within the dermis. Perineural plasma cell infiltrates may be a histologic clue to the diagnosis of cutaneous plasmacytosis. Observations. Our patient had a five-year history of persistent reddish-brown plaques on the neck and trunk without systemic symptoms. Histologic examination showed dermal perivascular and perineural plasma cells with excess lambda light chain expression. Due to decreased quality of life caused by his skin lesions, he was placed on a chemotherapeutic regimen with bortezomib. Conclusions and Relevance. The patient was diagnosed with cutaneous plasmacytosis based on classic histopathology results with a recently characterized pattern of perineural involvement. Bortezomib therapy was initiated to manage his skin eruption, which has not been previously described as a treatment for this chronic condition.
PubMed: 24839563
DOI: 10.1155/2014/840845