-
Annals of Surgery Jan 2024To develop a prediction model for long-term (≥5 years) disease-free survival (DFS) after the resection of pancreatic ductal adenocarcinoma (PDAC).
OBJECTIVE
To develop a prediction model for long-term (≥5 years) disease-free survival (DFS) after the resection of pancreatic ductal adenocarcinoma (PDAC).
BACKGROUND
Despite high recurrence rates, ~10% of patients have long-term DFS after PDAC resection. A model to predict long-term DFS may aid individualized prognostication and shared decision-making.
METHODS
This nationwide cohort study included all consecutive patients who underwent PDAC resection in the Netherlands (2014-2016). The best-performing prognostic model was selected by Cox-proportional hazard analysis and Akaike's Information Criterion, presented by hazard ratios (HRs) with 95% confidence intervals (CIs). Internal validation was performed, and discrimination and calibration indices were assessed.
RESULTS
In all, 836 patients with a median follow-up of 67 months (interquartile range 51-79) were analyzed. Long-term DFS was seen in 118 patients (14%). Factors predictive of long-term DFS were low preoperative carbohydrate antigen 19-9 (logarithmic; HR 1.21; 95% CI 1.10-1.32), no vascular resection (HR 1.33; 95% CI 1.12-1.58), T1 or T2 tumor stage (HR 1.52; 95% CI 1.14-2.04, and HR 1.17; 95% CI 0.98-1.39, respectively), well/moderate tumor differentiation (HR 1.44; 95% CI 1.22-1.68), absence of perineural and lymphovascular invasion (HR 1.42; 95% CI 1.11-1.81 and HR 1.14; 95% CI 0.96-1.36, respectively), N0 or N1 nodal status (HR 1.92; 95% CI 1.54-2.40, and HR 1.33; 95% CI 1.11-1.60, respectively), R0 resection margin status (HR 1.25; 95% CI 1.07-1.46), no major complications (HR 1.14; 95% CI 0.97-1.35) and adjuvant chemotherapy (HR 1.74; 95% CI 1.47-2.06). Moderate performance (concordance index 0.68) with adequate calibration (slope 0.99) was achieved.
CONCLUSIONS
The developed prediction model, readily available at www.pancreascalculator.com, can be used to estimate the probability of long-term DFS after resection of pancreatic ductal adenocarcinoma.
Topics: Humans; Cohort Studies; Disease-Free Survival; Neoplasm Recurrence, Local; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Prognosis; Retrospective Studies
PubMed: 37450706
DOI: 10.1097/SLA.0000000000006004 -
Journal of Orthopaedic Surgery and... May 2024This study aimed to compare the efficacy of intra-articular prolotherapy (IG) combined with peri-articular perineural injection (PG) in the management of knee... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
This study aimed to compare the efficacy of intra-articular prolotherapy (IG) combined with peri-articular perineural injection (PG) in the management of knee osteoarthritis (KOA).
METHODS
A total of 60 patients with the diagnosis of KOA were included in this double-blinded randomized controlled clinical trials. The inclusion criteria were as follow: (1) 48-80 years old; (2) the diagnose of KOA; (3) the grade 2 and 3 of the Kellgern-Lawrence grading scale; (4) the pain, crepitation, and knee joint stiffness continuing for 3 months at least. The main exclusion criteria were as follow: (1) any infection involving the knee skin; (2) history of any Influencing factors of disease. All patients were divided into three groups and received either IG, PG and I + PG under the ultrasound guidance and the 2, 4 and 8 weeks follow-up data of patients were available. (IG n = 20 or PG n = 20, I + PG n = 20). Visual Analogue Scale (VAS), The Western Ontario McMaster University Osteoarthritis Index (WOMAC) and the pressure pain threshold (PPT) were used as outcome measures at baseline, 2, 4 and 8 weeks.
RESULTS
There were no statistically significant differences in terms of age, sex, BMI, duration of current condition and baseline assessments of pain intensity, WOMAC scores and PPT. After treatment, the improvement of VAS activity, WOMAC and PPT values was showed compared with pre-treatment in all groups (p < 0.05). At 4 and 8 weeks after treatment, the VAS and WOMAC scores of the I + PG were significantly lower than those of the PG or IG, and the difference was statistically significant (p < 0.05). The PPT values of PG and I + PG were significantly improved compared to IG at 2, 4, and 8 weeks after treatment.
CONCLUSION
The ultrasound guided I + PG of 5% glucose seem to be more effective to alleviate pain and improve knee joint function than single therapy in short term. Clinical rehabilitators could clinically try this combination of I + PG to improve clinical symptoms in patients with KOA.
Topics: Humans; Osteoarthritis, Knee; Female; Male; Middle Aged; Injections, Intra-Articular; Prolotherapy; Aged; Double-Blind Method; Treatment Outcome; Aged, 80 and over; Pain Measurement; Ultrasonography, Interventional; Combined Modality Therapy
PubMed: 38705988
DOI: 10.1186/s13018-024-04762-4 -
Journal For Immunotherapy of Cancer Mar 2024The role of CD161 expression on CD8 T cells in tumor immunology has been explored in a few studies, and the clinical significance of CD161CD8 T cells in pancreatic...
BACKGROUND
The role of CD161 expression on CD8 T cells in tumor immunology has been explored in a few studies, and the clinical significance of CD161CD8 T cells in pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study seeks to clarify the prognostic value and molecular characteristics linked to CD161CD8 T cell infiltration in PDAC.
METHODS
This study included 186 patients with confirmed PDAC histology after radical resection. CD161CD8 T cell infiltration was assessed using immunofluorescence staining on tumor microarrays. Flow cytometry and single-cell RNA sequencing were used to evaluate their functional status.
RESULTS
We observed significant associations between tumor-infiltrating CD161CD8 T cells and clinicopathological factors, such as tumor differentiation, perineural invasion, and serum CA19-9 levels. Patients with higher tumor-infiltrating CD161CD8 T cell levels had longer overall survival (OS) and recurrence-free survival (RFS) than those with lower levels. Multivariable analysis confirmed tumor-infiltrating CD161CD8 T cell as an independent prognostic indicator for both OS and RFS. Notably, a combination of tumor-infiltrating CD161CD8 T cell and CA19-9 levels showed a superior power for survival prediction, and patients with low tumor-infiltrating CD161CD8 T cell and high CA19-9 levels had the worst survival. Furthermore, lower tumor-infiltrating CD161CD8 T cells were associated with a better response to adjuvant chemotherapy. Finally, we identified tumor-infiltrating CD161CD8 T cells as a unique subtype of responsive CD8 T cells characterized by increased levels of cytotoxic cytokines and immune checkpoint molecules.
CONCLUSION
CD161CD8 T cells exhibit elevated levels of both cytotoxic and immune-checkpoint molecules, indicating as a potential and attractive target for immunotherapy. The tumor-infiltrating CD161CD8 T cell is a valuable and promising predictor for survival and therapeutic response to adjuvant chemotherapy in PDAC. Further research is warranted to validate its role in the risk stratification and optimization of therapeutic strategies.
Topics: Humans; CD8-Positive T-Lymphocytes; CA-19-9 Antigen; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Prognosis
PubMed: 38531664
DOI: 10.1136/jitc-2023-008694 -
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 -
Actas Dermo-sifiliograficas 2023Atypical fibroxanthoma and pleomorphic dermal sarcoma (PDS) are rare mesenchymal tumors. Due to the low incidence of PDS and a historically confusing nomenclature,... (Observational Study)
Observational Study
BACKGROUND AND OBJECTIVE
Atypical fibroxanthoma and pleomorphic dermal sarcoma (PDS) are rare mesenchymal tumors. Due to the low incidence of PDS and a historically confusing nomenclature, little is known about the true aggressiveness of this tumor. The aim of this study was to investigate clinical and histologic risk factors for recurrence in PDS.
MATERIAL AND METHODS
Retrospective, observational, bicentric study of 31 PDSs diagnosed and treated at Hospital Clínico Universitario de Valencia and Instituto Valenciano de Oncología in Valencia, Spain, between 2005 and 2020. We described the clinical and histologic features of these tumors and performed univariate analysis and multivariate Cox regression analysis.
RESULTS
In the univariate analysis, tumor recurrence (P<.001), necrosis (P=.020), lymphovascular invasion (P=.037), perineural invasion (P=.041), and mitotic count (<18 vs ≥18 mitoses per 10 high-power fields) (P=.093) were associated with worse disease-free survival. In the multivariate Cox regression analysis, mitotic count and lymphovascular invasion retained their significance as predictors of worse disease-free survival (P<.05).
CONCLUSIONS
PDS is an aggressive tumor in which a high mitotic count (≥18) and lymphovascular invasion are associated with a higher risk of recurrence and worse disease-free survival. Necrosis and perineural invasion are also probably linked to increased tumor aggressiveness.
Topics: Humans; Bone Neoplasms; Necrosis; Neoplasm Recurrence, Local; Prognosis; Retrospective Studies; Sarcoma; Skin Neoplasms
PubMed: 37088288
DOI: 10.1016/j.ad.2023.04.018 -
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 Cellular and Molecular... Sep 2023The pancreatic stellate cells (PSCs) play an important role in the development of pancreatic cancer (PC) through mechanisms that remain unclear. Exosomes secreted from...
The pancreatic stellate cells (PSCs) play an important role in the development of pancreatic cancer (PC) through mechanisms that remain unclear. Exosomes secreted from PSCs act as mediators for communication in PC. This study aimed to explore the role of PSC-derived exosomal small RNAs derived from tRNAs (tDRs) in PC cells. Exosomes from PSCs were extracted and used to detect their effects on PC cell proliferation, migration and invasion. Exosomal tDRs profiling was performed to identify PSC-derived exosomal tDRs. ISH and qRT-PCR were used to examine the tRF-19-PNR8YPJZ levels and clinical value in clinical samples. The biological function of exosomal tRF-19-PNR8YPJZ was determined using the CCK-8, clone formation, wound healing and transwell assays, subcutaneous tumour formation and lung metastatic models. The relationship between the selected exosomal tRF-19-PNR8YPJZ and AXIN2 was determined by RNA sequencing, luciferase reporter assay. PSC-derived exosomes promoted the proliferation, migration, and invasion of PC cells. Novel and abundant tDRs are found to be differentially expressed in PANC-1 cells after treatment with PSC-derived exosomes, such as tRF-19-PNR8YPJZ. PC tissue samples showed markedly higher levels of tRF-19-PNR8YPJZ than normal controls. Patients with PC exhibiting high tRF-19-PNR8YPJZ expression had a highly lymph node invasion, metastasis, perineural invasion, advanced clinical stage and poor overall survival. Exosomal tRF-19-PNR8YPJZ from PSCs targeted AXIN2 in PC cells and decreased its expression, thus activating the Wnt pathway and promoting proliferation and metastasis. Exosomal tRF-19-PNR8YPJZ from PSCs promoted proliferation and metastasis in PC cells via AXIN2.
Topics: Humans; Pancreatic Stellate Cells; Cell Line, Tumor; Cell Movement; Pancreatic Neoplasms; Exosomes; Cell Proliferation; MicroRNAs; Axin Protein
PubMed: 37488774
DOI: 10.1111/jcmm.17852 -
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