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American Journal of Cancer Research 2024Perineural invasion and neurogenesis are frequently observed in pancreatic ductal adenocarcinoma (PDAC) and link to poor outcome. However, how neural factors affect PDAC...
Perineural invasion and neurogenesis are frequently observed in pancreatic ductal adenocarcinoma (PDAC) and link to poor outcome. However, how neural factors affect PDAC prognosis and the underlying mechanism as well as counteracting therapeutic are still unclear. systematic analysis was performed with PROGgene to identify potential neural factor and its receptor in pancreatic cancer. assays including migration, invasion, 3D recruitment, and gemcitabine resistance were performed to study the effect of neuron-derived neurotensin (NTS) on pancreatic cancer behavior. Orthotopic animal study was used to validate the findings. Gene set enrichment analysis (GSEA) was performed to confirm the results from to . Expression of NTS and its receptor 1 (NTSR1) predicted poor prognosis in PDAC. NTS synthetic peptide or neuron-derived condition medium promoted pancreatic cancer invasiveness and recruitment in 2D and 3D assays. NTS-induced effects depended on NTSR1 and PI3K activation. GDC-0941, a clinically approved PI3K inhibitor, counteracted NTS-induced effects . Inhibition of NTSR1 in pancreatic cancer cells resulted in decreased tumor dissemination and diminished PI3K activation . NTS boosted gemcitabine resistance via NTSR1 in pancreatic cancer. Our results suggest that neural cell-secreted NTS plays an important role in promoting PDAC.
PubMed: 38455426
DOI: 10.62347/UAKN9541 -
Pathology, Research and Practice Oct 2023Pulmonary adenocarcinoma shows different prognosis even in the same pathological subtype and stage. In this study, it is aimed to investigate the relationship between...
BACKGROUND
Pulmonary adenocarcinoma shows different prognosis even in the same pathological subtype and stage. In this study, it is aimed to investigate the relationship between tumour budding and known prognostic values and clinicopathological features in pulmonary adenocarcinoma.
METHODS
In this study, there have been 77 patients diagnosed with primary pulmonary adenocarcinoma. In the evaluation process, the number of budding between 0 and 4 is accepted as low budding (Bd1), the number of budding between 5 and 9 is considered as medium budding (Bd2), and the number of budding above 10 is considered as high budding (Bd3).
RESULTS
According to the findings of the study, it can be seen that there is a statistical difference between tumour budding and stromal fibrosis (p < 0.001). The presence of pleural invasion, lymph vascular invasion and perineural invasion in patients with Bd3 is found to be statistically higher than the patients with Bd1 (p = 0.048) (p = 0.041) (p = 0.029).
CONCLUSIONS
Tumour budding has been associated with pleural invasion, lymph vascular invasion, perineural invasion, and stromal fibrosis. This study is the first to show the relationship between tumour budding and stromal fibrosis in pulmonary adenocarcinomas. The role of tumour budding in lung cancers remains to be clarified.
PubMed: 37748210
DOI: 10.1016/j.prp.2023.154808 -
Journal of Oral and Maxillofacial... May 2024Head and neck osteosarcoma (HNOS) is the most common bone malignancy in the head and neck region, accounting for 10% of all osteosarcoma cases. Perineural invasion (PNI)...
BACKGROUND
Head and neck osteosarcoma (HNOS) is the most common bone malignancy in the head and neck region, accounting for 10% of all osteosarcoma cases. Perineural invasion (PNI) is a notable indication of aggressive tumor behavior, which includes the phenomenon of tumor cells invading any of the 3 layers of the nerve sheath or tumor cells gathering, encircling one-third of the nerve circumference, and infiltrating and metastasizing along the nerve. PNI has been reported in various malignant tumors and is considered to be linked to poor prognosis.
PURPOSE
The study's purpose is to measure the association between PNI and survival outcomes in patients with HNOS.
STUDY DESIGN, SETTING, SAMPLE
This retrospective cohort study focused on HNOS patients who underwent surgery at the Department of Oral and Maxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital School of Medicine, Shanghai Jiao Tong University, from January 1, 2019 to December 31, 2021. Patients who did not undergo complete surgical resection of the tumor, did not receive a conventional osteosarcoma diagnosis, and had positive surgical margins were eliminated.
PREDICTOR VARIABLE
The predictor variable is PNI status. The pathological section of the tumor was consistent with any of the PNI features, which was considered PNI-positive.
MAIN OUTCOME VARIABLE(S)
The primary outcome variables were 3-year disease-free survival (DFS) and 3-year overall survival. Secondary outcomes were 3-year tumor local recurrence and 3-year metastasis (MT).
COVARIATES
Covariates were categorized into the following categories: demographic variables (age, sex), clinical variables (tumor region, primary tumor), and treatment variables (chemotherapy, radiotherapy).
ANALYSES
Analytic statistical methods were used for the data analysis. Pearson χ or Fisher's exact test was used to describe the baseline data. Kaplan-Meier is used to calculate survival rates. The Cox regression model was adapted for univariate and multivariate analysis. A P value less than .05 indicated statistical significance.
RESULTS
The study sample comprised 70 patients; 33 (47.1%) were male, and the mean age was 42.2 (standard deviation: 16.7) years. There were 15 (21.4%) cases of PNI. The 3-year DSF rate and OS rate were 67.3% and 82.0%, respectively. PNI-positive resulted in higher risk for MT (P < .01, hazard ratio: 5.95, 95% confidence interval: 1.62-21.86) and negative impact on DFS (P < .01, hazard ratio: 6.35, 95% confidence interval: 2.11-19.17) for HNOS patients.
CONCLUSION AND RELEVANCE
Positive PNI status was associated with decreased DFS and increased risk of MT.
PubMed: 38797510
DOI: 10.1016/j.joms.2024.05.001 -
International Journal of Surgery... Feb 2024Perineural invasion (PNI) of intrahepatic cholangiocarcinoma (ICC) is a strong independent risk factor for tumour recurrence and long-term patient survival. However,...
Noninvasive prediction of perineural invasion in intrahepatic cholangiocarcinoma by clinicoradiological features and computed tomography radiomics based on interpretable machine learning: a multicenter cohort study.
BACKGROUND
Perineural invasion (PNI) of intrahepatic cholangiocarcinoma (ICC) is a strong independent risk factor for tumour recurrence and long-term patient survival. However, there is a lack of noninvasive tools for accurately predicting the PNI status. The authors develop and validate a combined model incorporating radiomics signature and clinicoradiological features based on machine learning for predicting PNI in ICC, and used the Shapley Additive explanation (SHAP) to visualize the prediction process for clinical application.
METHODS
This retrospective and prospective study included 243 patients with pathologically diagnosed ICC (training, n =136; external validation, n =81; prospective, n =26, respectively) who underwent preoperative contrast-enhanced computed tomography between January 2012 and May 2023 at three institutions (three tertiary referral centres in Guangdong Province, China). The ElasticNet was applied to select radiomics features and construct signature derived from computed tomography images, and univariate and multivariate analyses by logistic regression were used to identify the significant clinical and radiological variables with PNI. A robust combined model incorporating radiomics signature and clinicoradiological features based on machine learning was developed and the SHAP was used to visualize the prediction process. A Kaplan-Meier survival analysis was performed to compare prognostic differences between PNI-positive and PNI-negative groups and was conducted to explore the prognostic information of the combined model.
RESULTS
Among 243 patients (mean age, 61.2 years ± 11.0 (SD); 152 men and 91 women), 108 (44.4%) were diagnosed as PNI-positive. The radiomics signature was constructed by seven radiomics features, with areas under the curves of 0.792, 0.748, and 0.729 in the training, external validation, and prospective cohorts, respectively. Three significant clinicoradiological features were selected and combined with radiomics signature to construct a combined model using machine learning. The eXtreme Gradient Boosting exhibited improved accuracy and robustness (areas under the curves of 0.884, 0.831, and 0.831, respectively). Survival analysis showed the construction combined model could be used to stratify relapse-free survival (hazard ratio, 1.933; 95% CI: 1.093-3.418; P =0.021).
CONCLUSIONS
We developed and validated a robust combined model incorporating radiomics signature and clinicoradiological features based on machine learning to accurately identify the PNI statuses of ICC, and visualize the prediction process through SHAP for clinical application.
Topics: Female; Humans; Male; Middle Aged; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Machine Learning; Prospective Studies; Radiomics; Retrospective Studies; Tomography, X-Ray Computed
PubMed: 37924497
DOI: 10.1097/JS9.0000000000000881 -
JAMA Dermatology Aug 2023The extent to which major high-risk features of squamous cell carcinomas (SCCs) in organ transplant recipients (OTRs) differ from SCCs in the general population is not...
IMPORTANCE
The extent to which major high-risk features of squamous cell carcinomas (SCCs) in organ transplant recipients (OTRs) differ from SCCs in the general population is not known.
OBJECTIVE
To quantify the relative frequency of perineural invasion, invasion below the dermis, lack of cellular differentiation, and tumor diameter greater than 20 mm in SCCs in OTRs and the general population, by anatomic site.
DESIGN, SETTING, AND PARTICIPANTS
This dual-cohort study in Queensland, Australia, included a cohort of OTRs at high risk of skin cancer ascertained from 2012 to 2015 (Skin Tumours in Allograft Recipients [STAR] study) and a population-based cohort ascertained from 2011 (QSkin Sun and Health Study). The STAR study comprised population-based lung transplant recipients and kidney and liver transplant recipients at high risk of skin cancer recruited from tertiary centers and diagnosed with histopathologically confirmed SCC from 2012 to 2015. The QSkin participants were recruited from Queensland's general adult population, and primary SCCs diagnosed from 2012 to 2015 were ascertained through Medicare (national health insurance scheme) and linked with histopathology records. Data analysis was performed from July 2022 to April 2023.
MAIN OUTCOMES AND MEASURES
Prevalence ratio (PR) of head/neck location, perineural invasion, tumor invasion to/beyond subcutaneous fat, poor cellular differentiation, and tumor diameter greater than 20 mm among SCCs in OTRs vs the general population.
RESULTS
There were 741 SCCs excised from 191 OTRs (median [IQR] age, 62.7 [56.7-67.1] years; 149 [78.0%] male) and 2558 SCCs from 1507 persons in the general population (median [IQR] age, 63.7 [58.0-68.8] years; 955 [63.4%] male). The SCCs developed most frequently on the head/neck in OTRs (285, 38.6%), but on arms/hands in the general population (896, 35.2%) (P < .001). After adjusting for age and sex, perineural invasion was more than twice as common in OTRs as in population cases (PR, 2.37; 95% CI, 1.70-3.30), as was invasion to/beyond subcutaneous fat (PR, 2.37; 95% CI, 1.78-3.14). Poorly vs well-differentiated SCCs were more than 3-fold more common in OTRs (PR, 3.45; 95% CI, 2.53-4.71), and prevalence of tumors greater than 20 mm vs 20 mm or smaller was moderately higher in OTRs (PR, 1.52; 95% CI, 1.08-2.12).
CONCLUSIONS AND RELEVANCE
In this dual-cohort study, SCCs in OTRs had significantly worse prognostic features than SCCs in the general population, reinforcing the necessity of early diagnosis and definitive management of SCCs in OTRs.
Topics: Adult; Humans; Male; Aged; Middle Aged; Female; Cohort Studies; Prognosis; National Health Programs; Carcinoma, Squamous Cell; Skin Neoplasms; Organ Transplantation; Transplant Recipients
PubMed: 37314794
DOI: 10.1001/jamadermatol.2023.1574 -
Journal of Personalized Medicine Jan 2024Ultrasound-guided perineural hydrodissection (HD) is a novel technique that has been found to be effective in providing mechanical release of perineural adhesions and... (Review)
Review
Ultrasound-guided perineural hydrodissection (HD) is a novel technique that has been found to be effective in providing mechanical release of perineural adhesions and decompression of the nerve, reducing inflammation and edema and restoring its physiological function. It has a significant impact on chronic neuropathic pain (20 ± 4 weeks with VAS < 5 or VAS diminished by 2 points after the procedure). Carpal tunnel syndrome (CTS) is a common entrapment mononeuropathy, and its distribution is typically innervated by the median nerve. Patients with mild or moderate CTS may benefit from nonsurgical treatments or conservative therapies. This review was conducted following the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement guidelines. Four investigators assessed each title, abstract, and full-text article for eligibility, with disagreements being resolved by consensus with two experienced investigators. The qualitative assessment of the studies was carried out using the modified Oxford quality scoring system, also known as the modified Jadad score. Furthermore, risk of possible biases was assessed using the Cochrane collaboration tool. The results of this review suggest that US-guided HD is an innovative, effective, well-tolerated, and safe technique (11 out of 923 patients had collateral or side effects after the procedure). However, further studies comparing all drugs and with a larger sample population are required to determine the most effective substance.
PubMed: 38392587
DOI: 10.3390/jpm14020154 -
Cells Jan 2024The neurobiology of tumors has attracted considerable interest from clinicians and scientists and has become a multidisciplinary area of research. Neural components not... (Review)
Review
The neurobiology of tumors has attracted considerable interest from clinicians and scientists and has become a multidisciplinary area of research. Neural components not only interact with tumor cells but also influence other elements within the TME, such as immune cells and vascular components, forming a polygonal relationship to synergistically facilitate tumor growth and progression. This review comprehensively summarizes the current state of the knowledge on nerve-tumor crosstalk in head and neck cancer and discusses the potential underlying mechanisms. Several mechanisms facilitating nerve-tumor crosstalk are covered, such as perineural invasion, axonogenesis, neurogenesis, neural reprogramming, and transdifferentiation, and the reciprocal interactions between the nervous and immune systems in the TME are also discussed in this review. Further understanding of the nerve-tumor crosstalk in the TME of head and neck cancer may provide new nerve-targeted treatment options and help improve clinical outcomes for patients.
Topics: Humans; Head and Neck Neoplasms; Cell Transdifferentiation; Nerve Tissue
PubMed: 38334648
DOI: 10.3390/cells13030256 -
Biomedicines Sep 2023Thick cutaneous melanomas (Breslow depth > 4 mm) are locally advanced tumors, generally associated with poor prognosis. Nevertheless, these tumors sometimes display...
Thick cutaneous melanomas (Breslow depth > 4 mm) are locally advanced tumors, generally associated with poor prognosis. Nevertheless, these tumors sometimes display unpredictable behavior. This study aims to analyze clinical and histopathological features that can influence the prognosis of thick melanomas. This is a retrospective study on 94 thick primary cutaneous melanomas diagnosed between 2012 and 2018 that were followed-up for at least five years to assess disease progression and survival. We evaluated the age, gender, tumor location, histological subtype, Breslow depth, Clark level, resection margins, mitotic index, the presence/absence of ulceration, necrosis, regression, microsatellites, neurotropism, lymphovascular invasion, and the pattern of tumor-infiltrating lymphocytes, and their association with disease progression and survival. By conducting univariate analysis, we found that progression-free survival (PFS) was significantly associated with female gender, the superficial spreading melanoma (SSM) subtype, mitotic index, necrosis, microsatellites, and perineural invasion. Overall survival (OS) was significantly associated with female gender, Breslow depth, SSM subtype, necrosis, microsatellites, and perineural invasion. Through multivariate Cox proportional hazards regression, we found that the only factors associated with PFS were Breslow depth, necrosis, microsatellites, and perineural invasion, while the factors associated with OS were Breslow depth, necrosis, microsatellites, and perineural invasion. Certain histopathological features such as Breslow depth, necrosis, microsatellites, and perineural invasion could explain differences in disease evolution. This is one of the first studies to demonstrate an association between necrosis and perineural invasion and outcomes in patients with thick melanomas. By identifying high-risk patients, personalized therapy can be provided for improved prognosis.
PubMed: 37892990
DOI: 10.3390/biomedicines11102616 -
Clinical Oncology (Royal College of... Oct 2023Perineural invasion (PNI) is a special type of metastasis of several cancers and has been reported as being a factor for poor prognosis in colorectal carcinoma. However,... (Meta-Analysis)
Meta-Analysis
AIMS
Perineural invasion (PNI) is a special type of metastasis of several cancers and has been reported as being a factor for poor prognosis in colorectal carcinoma. However, investigations of PNI in only rectal cancer and a comprehensive analysis combining meta-analyses with real-world case studies remain lacking.
MATERIALS AND METHODS
First, articles from 2000 to 2020 concerning the relationship between PNI and rectal cancer prognoses and clinical features were meta-analysed. Subsequently, we carried out a retrospective analysis of 312 rectal cancer cases that underwent radical surgery in the real world. The incidence of PNI and the relationship between PNI and prognosis, as well as clinicopathological factors, were investigated.
RESULTS
The incidence of PNI was 23.09% and 33.01% in the meta-analysis and clinical cases, respectively. PNI occurred as early as stage I (2.94%). Moreover, neoadjuvant therapy significantly reduced the PNI-positive rate (20.34% versus 26.54%). Both meta-analysis and real-world clinical case studies suggested that PNI-positive patients had poorer prognoses than PNI-negative patients. We established an effective risk model consisting of T stage, differentiation and lymphovascular invasion to predict PNI in rectal cancer.
CONCLUSION
PNI is a poor prognostic factor for rectal cancer and could occur even in stage I. Additionally, neoadjuvant therapy could sufficiently reduce the PNI-positive rate. T stage, lymphovascular invasion and differentiation grade were independent risk factors for PNI and the risk model that included these factors could predict the probability of PNI.
Topics: Humans; Retrospective Studies; Incidence; Neoplasm Invasiveness; Prognosis; Rectal Neoplasms; Carcinoma; Neoplasm Staging
PubMed: 37263883
DOI: 10.1016/j.clon.2023.05.008 -
The Journal of Urology Oct 2023We assessed the prognostic significance of quantification of perineural invasion on prostate biopsy.
PURPOSE
We assessed the prognostic significance of quantification of perineural invasion on prostate biopsy.
MATERIALS AND METHODS
We quantified actual perineural invasion foci in the entire prostate biopsy specimens from 724 patients and compared corresponding radical prostatectomy findings and long-term oncologic outcomes.
RESULTS
No perineural invasion was detected in 524 (72.4%) prostate biopsies, whereas 1 (n=129; 17.8%), 2 (n=40; 5.5%), 3 (n=18; 2.5%), 4 (n=7; 1.0%), and 5-10 (n=6; 0.8%) perineural invasion foci were present in other cases. We confirmed a higher risk of recurrence after radical prostatectomy in patients with perineural invasion on prostate biopsy than in those with no perineural invasion ( < .001). Remarkably, recurrence-free survival was comparable between those with 0 vs 1 perineural invasion ( = .9) or 2 vs ≥3 perineural invasions ( = .3). Nonetheless, multifocal perineural invasion per prostate biopsy (vs single perineural invasion; < .001) and >1 perineural invasion per 10-mm tumor (vs ≤1 perineural invasion; = .008) were associated with worse outcomes. Interestingly, in a subgroup outcome analysis of single vs multifocal perineural invasions per prostate biopsy, there was a significant difference in patients showing perineural invasion involving only 1 of the sextant sites. In multivariable analysis, both multifocal perineural invasion/case (HR=5.48, < .001) and >1 perineural invasion/10-mm tumor (HR=3.96, < .001) showed significance for recurrence. Meanwhile, compared with CAPRA (Cancer of the Prostate Risk Assessment) score alone (0.687/0.685), Harrell's C index/AUC for predicting 5-year recurrence-free survival was gradually increased when 1 (0.722/0.740), 2 (0.747/0.773), or 3 (0.760/0.792) point(s) were additionally assigned to multifocal perineural invasion.
CONCLUSIONS
Multifocal perineural invasion and >1 perineural invasion per 10-mm tumor on each prostate biopsy were thus found to be associated with poorer prognosis, as independent predictors, in men with prostate cancer undergoing radical prostatectomy.
Topics: Male; Humans; Prostate; Neoplasm Invasiveness; Prostatic Neoplasms; Biopsy, Large-Core Needle; Prostatectomy; Biopsy; Risk Assessment
PubMed: 37433144
DOI: 10.1097/JU.0000000000003618