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Biomedical Papers of the Medical... Dec 2019Oral squamous cell carcinoma (OSCC) is a growing problem worldwide. Several biological and molecular criteria have been established for making a prognosis of OSCC. One...
Oral squamous cell carcinoma (OSCC) is a growing problem worldwide. Several biological and molecular criteria have been established for making a prognosis of OSCC. One of the most important factors affecting the risk of tumor recurrence and overall prognosis is perineural invasion and bone invasion. Perineural invasion is defined as a tumor spreading and the ability of tumor cells to penetrate around or through the nerve tissue. Perineural invasion can cause the tumor to spread to distant areas from the primary tumor location. One possible explanation for this is the formation of microenvironment in the perineural space which may contain cellular factors that act on both nerve tissue and some types of tumor tissues. Bone invasion by OSCC has major implications for tumor staging, choice of treatment, outcome and quality of life. Oral SCCs invade the mandibular or maxillary bone through an erosive, infiltrative or mixed pattern that correlates with clinical behavior. Bone resorption by osteoclasts is an important step in the process of bone invasion by oral SCCs. Some cytokines (e.g. TNFα and PTHrP) lead to receptor activator of NF-κB ligand (RANKL) expression or osteoprotegerin (OPG) suppression in oral SCC cells and in cancer stromal cells to induce osteoclastogenesis. Oral SCCs provide a suitable microenvironment for osteoclastogenesis to regulate the balance of RANKL and OPG. A more molecular-based clinical staging and tailor-made therapy would benefit patients with bone invasion by OSCC.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Bone Neoplasms; Carcinoma, Squamous Cell; Cytokines; Female; Humans; Male; Middle Aged; Mouth Neoplasms; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Nerve Sheath Neoplasms; Predictive Value of Tests; Prognosis
PubMed: 31435075
DOI: 10.5507/bp.2019.032 -
ANZ Journal of Surgery Sep 2022To present an institution's experience and survival outcomes for patients with head and neck cutaneous squamous cell carcinoma (HNcSCC) and perineural spread (PNS).
AIM
To present an institution's experience and survival outcomes for patients with head and neck cutaneous squamous cell carcinoma (HNcSCC) and perineural spread (PNS).
METHOD
Retrospective study of patients with HNcSCC and PNS treated between January 2010 and August 2020 from the Sydney Head and Neck Cancer Institute database, Sydney, Australia; a high-volume, tertiary, academic head and neck centre. Patient demographics, primary site, involved cranial nerves, treatment modality, loco-regional failure and survival data were obtained.
RESULTS
Forty-five patients were identified, of which 32 patients were male (71%). Mean age at diagnosis was 68.7 years (range 43-90). Median follow-up was 16.1 months (range 1-107). The trigeminal nerve was most frequently involved (n = 30, 66.6%) followed by facial nerve (n = 13, 28.9%). Most patients underwent surgery followed by radiotherapy (n = 33, 73%) and eight received definitive radiotherapy. The median overall survival (OS) was 4.5 years (95% CI 3.71-5.38), median disease-specific survival 5.1 years (95% CI 4.21-5.97) and median disease-free survival (DFS) was 1.7 years (95% CI 1.11-2.22). The estimated 5-year OS and DFS were 45% and 25%, respectively. Patients treated with surgery and adjuvant radiotherapy with a clear proximal nerve margin had favourable DFS (P = 0.035) and trended towards better OS (P = 0.134) compared with patients with an involved nerve margin. Patients treated surgically with involved proximal nerve margins had similar outcomes compared with patients with treated definitive radiotherapy (HR 0.80, 95% CI 0.29-2.22, P = 0.664).
CONCLUSION
The likelihood of achieving a clear proximal nerve margin should be a strong consideration in the selection of appropriate patients for primary surgery.
Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Disease-Free Survival; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Retrospective Studies; Skin Neoplasms; Squamous Cell Carcinoma of Head and Neck
PubMed: 35866314
DOI: 10.1111/ans.17908 -
Frontiers in Oncology 2022Although patients with oral squamous cell carcinoma who develop contralateral neck metastasis (CLNM) have worse survival outcomes than those without CLNM, accurate...
Midline involvement and perineural invasion predict contralateral neck metastasis that affects overall and disease-free survival in locally advanced oral tongue squamous cell carcinoma.
INTRODUCTION
Although patients with oral squamous cell carcinoma who develop contralateral neck metastasis (CLNM) have worse survival outcomes than those without CLNM, accurate prediction of occult CLNM in clinically negative contralateral neck (contralateral cN0) remains difficult. This study aimed to identify clinicopathological factors that could reliably predict CLNM in patients with locally advanced (clinical T3 and T4a) tongue squamous cell carcinoma (TSCC).
PATIENTS AND METHODS
The medical data of 32 patients with cT3-4a TSCC who underwent curative surgery between 2010 and 2017 were retrospectively analyzed. The correlation of clinicopathological variables with CLNM was examined using logistic regression analysis. The diagnostic performance of significant variables was evaluated using the area under the receiver operating characteristic curves (AUC). Overall survival (OS) and disease-free survival (DFS) were assessed using a Cox proportional hazards model.
RESULTS
CLNM was eventually confirmed in 11 patients (34.4%). Multivariate logistic regression showed that midline involvement [odds ratio (OR) = 23.10, P = 0.017] and perineural invasion (PNI, OR = 14.96, P = 0.014) were independent predictors of CLNM. Notably, the prediction model comprising a combination of midline involvement and PNI exhibited superior diagnostic performance with an even higher OR of 80.00 (P < 0.001), accuracy of 90.3%, and AUC of 0.876. The multivariate Cox hazards model revealed independent significance of CLNM as an unfavorable prognostic factor for both OS [hazard ratio (HR) = 5.154, P = 0.031] and DFS (HR = 3.359, P = 0.038), as well as that of PNI for OS (HR = 5.623, P = 0.033).
CONCLUSION
Our findings suggest that coexisting midline involvement and PNI of the primary tumor is highly predictive of CLNM development, which independently affects both OS and DFS in patients with locally advanced TSCC. Such reliable prediction enables efficient control of CLNM by optimizing management of the contralateral cN0 neck, which will likely contribute to improved prognosis of those patients without unnecessarily compromising their quality of life.
PubMed: 36387194
DOI: 10.3389/fonc.2022.1010252 -
Modern Pathology : An Official Journal... Feb 2023Adenoid cystic carcinoma (AdCC) is an uncommon type of invasive breast carcinoma with a favorable prognosis. However, some cases are aggressive. The study aims to define...
Adenoid cystic carcinoma (AdCC) is an uncommon type of invasive breast carcinoma with a favorable prognosis. However, some cases are aggressive. The study aims to define the clinicopathologic predictors of outcome. Clinical, radiological, and pathologic variables were recorded for 76 AdCC cases from 11 institutions. The following histologic characteristics were evaluated by the breast pathologist in each respective institution, including Nottingham grade (NG), percentages of various growth patterns (solid, cribriform, trabecular-tubular), percentage of basaloid component, tumor borders (pushing, infiltrative), perineural invasion, lymphovascular invasion, necrosis, and distance from the closest margin. Various grading systems were evaluated, including NG, salivary gland-type grading systems, and a new proposed grading system. The new grading system incorporated the growth pattern (percent solid, percent cribriform), percent basaloid morphology, and mitotic count using the Youden index criterion. All variables were correlated with recurrence-free survival. Nineteen (25%) women developed local and/or distant recurrence. Basaloid morphology (≥25% of the tumor) was identified in 20 (26.3%) cases and a solid growth pattern (using ≥60% cutoff) in 22 (28.9%) cases. In the univariate analysis, the following variables were significantly correlated with worse recurrence-free survival: solid growth pattern, basaloid morphology, lymphovascular invasion, necrosis, perineural invasion, and pN-stage. In the multivariate analysis including basaloid morphology, pN-stage, lymphovascular invasion, and perineural invasion, basaloid morphology was statistically significant, with a hazard ratio of 3.872 (95% CI, 1.077; 13.924; P =.038). The NG and the new grading system both correlated with recurrence-free survival. However, grade 2 had a similar risk as grade 3 in the NG system and a similar risk as grade 1 in the new grading system. For solid growth patterns and basaloid morphology, using a 2-tier system with 1 cutoff was better than a 3-tier system with 2 cutoffs. Basaloid morphology and solid growth pattern have prognostic values for AdCC, with a 2-tier grading system performing better than a 3-tier system.
Topics: Female; Humans; Carcinoma, Adenoid Cystic; Breast Neoplasms; Breast; Cell Cycle; Necrosis
PubMed: 36853781
DOI: 10.1016/j.modpat.2022.100006 -
Cancers Feb 2023Perineural invasion (PNI) as the fourth way for solid tumors metastasis and invasion has attracted a lot of attention, recent research reported a new point that PNI... (Review)
Review
Perineural invasion (PNI) as the fourth way for solid tumors metastasis and invasion has attracted a lot of attention, recent research reported a new point that PNI starts to include axon growth and possible nerve "invasion" to tumors as the component. More and more tumor-nerve crosstalk has been explored to explain the internal mechanism for tumor microenvironment (TME) of some types of tumors tends to observe nerve infiltration. As is well known, the interaction of tumor cells, peripheral blood vessels, extracellular matrix, other non-malignant cells, and signal molecules in TME plays a key role in the occurrence, development, and metastasis of cancer, as to the occurrence and development of PNI. We aim to summarize the current theories on the molecular mediators and pathogenesis of PNI, add the latest scientific research progress, and explore the use of single-cell spatial transcriptomics in this invasion way. A better understanding of PNI may help to understand tumor metastasis and recurrence and will be beneficial for improving staging strategies, new treatment methods, and even paradigm shifts in our treatment of patients.
PubMed: 36900158
DOI: 10.3390/cancers15051360 -
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 -
Acta Otorhinolaryngologica Italica :... Apr 2022The aim of this study was to investigate the relationship between differentiated thyroid carcinomas (DTCs), histopathological findings and systemic immune-inflammation...
OBJECTIVE
The aim of this study was to investigate the relationship between differentiated thyroid carcinomas (DTCs), histopathological findings and systemic immune-inflammation index (SII) [neutrophil (N) x platelet (P) / lymphocyte (L)] values.
METHODS
93 patients with DTC were included. N, P and L levels were measured, and the relationship between the SII and histopathological findings was determined. The results were compared with the values of 33 healthy controls.
RESULTS
SII values were significantly higher in the patient group than in the control group (p = 0.000). Tumour pathology diagnosis had no significant effect on SII (p = 0.90). Perineural lymphovascular and capsule invasion and extrathyroidal extension also had no significant effect on SII values. SII was significantly higher in patients with more than one tumour focus (p = 0.01). No significant relationship was determined between tumour diameter and SII.
CONCLUSIONS
SII is higher in patients with DTC compared to the healthy population. High SII values may be associated with multifocality. According to the results of this study, SII does not affect the histological type, perineural, lymphovascular and capsule invasion, or extrathyroidal extension of DTC.
Topics: Blood Platelets; Humans; Inflammation; Lymphocytes; Neutrophils; Prognosis; Retrospective Studies; Thyroid Neoplasms
PubMed: 35612506
DOI: 10.14639/0392-100X-N1665 -
Frontiers in Oncology 2020Adenoid cystic carcinoma of the salivary gland (SACC) is a rare malignant tumors of the head and neck region, but it is one of the most common malignant tumors that are... (Review)
Review
Adenoid cystic carcinoma of the salivary gland (SACC) is a rare malignant tumors of the head and neck region, but it is one of the most common malignant tumors that are prone to perineural invasion (PNI) of the head and neck. The prognosis of patients with SACC is strongly associated with the presence of perineural spread (PNS). Although many contributing factors have been reported, the mechanisms underlying the preferential destruction of the blood-nerve barrier (BNB) by tumors and the infiltration of the tumor microenvironment by nerve fibers in SACC, have received little research attention. This review summarizes the current knowledge concerning the characteristics of SACC in relation to the PNI, and then highlights the interplay between components of the tumor microenvironment and perineural niche, as well as their contributions to the PNI. Finally, we provide new insights into the possible mechanisms underlying the pathogenesis of PNI, with particular emphasis on the role of extracellular vesicles that may serve as an attractive entry point in future studies.
PubMed: 33014792
DOI: 10.3389/fonc.2020.01493 -
Asian Journal of Surgery Dec 2022Pancreatic neuroendocrine tumors (P-NETs) are highly heterogeneous with wide spectrum of biological behaviors and growth patterns. Here, we aimed to assess the impact of...
BACKGROUND/OBJECTIVE
Pancreatic neuroendocrine tumors (P-NETs) are highly heterogeneous with wide spectrum of biological behaviors and growth patterns. Here, we aimed to assess the impact of tumor grading on P-NETs prognosis and survival outcomes.
METHODS
Patients with P-NET were recruited to determine correlations between grades and clinicopathological factors, survival outcomes and prognostic factors.
RESULT
A total of 152 patients with P-NETs were enrolled. G1 P-NET were associated with significantly lower rates of perineural invasion, lymphovascular invasion, lymph node involvement and distant metastasis. The pancreatic head was the most common location of P-NETs. The 1-year, 5-year and 10-year overall survival rates of the patients were 94.4%, 89.1% and 78.8%, respectively. Majority of pancreatic neuroendocrine carcinoma (P-NEC) were unresectable (90.9%), and P-NECs patients had poor survival rates (1-year, 20% and no 5-year). Male sex, tumor size ≥2.5 cm, perineural invasion, lymph node invasion, metastasis, and advanced stage were significantly associated with poorer survival outcomes. Tumor grade and sex were independent survival predictors. Moreover, tumor grade was the most powerful prognostic factor.
CONCLUSIONS
Tumor grade, sex, perineural invasion, tumor size, lymph node involvement, metastasis, and stage are survival predictors for patients with P-NETs. Tumor grade is the most powerful independent prognostic factor.
Topics: Humans; Male; Infant, Newborn; Neuroendocrine Tumors; Pancreatic Neoplasms; Retrospective Studies; Prognosis; Neoplasm Grading
PubMed: 35246343
DOI: 10.1016/j.asjsur.2022.01.094 -
Balkan Medical Journal Nov 2022Extramural venous invasion is an independent predictor of poor outcome in colorectal cancer, whereas the significance of the intramural component of venous and lymphatic...
BACKGROUND
Extramural venous invasion is an independent predictor of poor outcome in colorectal cancer, whereas the significance of the intramural component of venous and lymphatic and perineural invasion is unclear.
AIMS
To evaluate the prognostic impact of intramural components for venous, lymphatic, and perineural invasions and the relation of these invasion patterns with clinicopathological features in patients with colon cancer.
STUDY DESIGN
A retrospective cross-sectional study.
METHODS
The analysis included 626 patients with colon cancer in stages II and III. All patients were divided into four categories (no invasion, intramural invasion only, extramural invasion only, or both intramural and extramural invasions) for vascular invasion, lymphatic invasion and perineural invasion. The primary outcomes were 5-year disease-free and overall survival.
RESULTS
Right-sided (for vascular invasion, 24.7% vs. 33.9%, = 0.007; for perineural invasion, 34.5% vs. 41.5%, = 0.034) and dMMR tumors (for vascular invasion, 13.5% vs. 33.5, < 0.001; for perineural invasion, 25% vs. 41.4%, = 0.004) exhibited less venous and perineural invasion. Compared with no invasion, presence of intramural invasion only, did not exert any effect on disease-free or overall survival for vascular invasion, lymphatic invasion, and perineural invasion. Multivariate analyses revealed that the presence of both intramural and extramural invasion was independently associated with poor disease-free and overall survival for venous (hazard ratios: 2.39, = 0.001; hazard ratios: 2.46, = 0.001), lymphatic (hazard ratios: 2.456, < 0.001; hazard ratios: 2.13, = 0.02) and perineural invasion (hazard ratios: 2.99, < 0.001; hazard ratios: 2.68, < 0.001), respectively.
CONCLUSION
Our data strongly advocates the importance of reporting intramural and extramural components of invasion since the presence of intramural invasion alone may not be considered as a high-risk factor for systemic recurrence.
Topics: Humans; Colonic Neoplasms; Cross-Sectional Studies; Neoplasm Invasiveness; Neoplasm Staging; Retrospective Studies
PubMed: 36317726
DOI: 10.4274/balkanmedj.galenos.2022.2022-6-94