M1 Stage Research Articles

Construction and Validation of a Prognostic Prediction Model for Gastric Mucinous Adenocarcinoma Based on the SEER Database

This study focused on the development and validation of a prognostic model to predict overall survival (OS) in patients with gastric mucinous adenocarcinoma (GMA), utilizing data from the SEER database. A cohort of 537 GMA patients was analyzed to identify factors affecting survival, using both univariate and multivariate Cox regression analyses on demographic and clinicopathological variables. The analysis led to the creation of a nomogram model. Findings revealed that TNM staging and the administration of radiotherapy or chemotherapy were significant factors impacting survival outcomes. Specifically, patients at stages T4, N3, and M1 faced a notably higher mortality risk, while those who received radiotherapy and chemotherapy experienced a significant reduction in mortality risk. The model's performance, as indicated by C-indices of 0.73 in the training set and 0.66 in the validation set, suggests robust predictive capability. The area under the curve (AUC) analysis confirmed high accuracy in predicting 1-year, 3-year, and 5-year survival rates, and calibration curves displayed strong agreement between predicted and actual outcomes. Decision curve analysis (DCA) demonstrated that the model exhibited significant clinical utility across various thresholds. Overall, this study presents a reliable prognostic tool for individualized risk stratification and clinical treatment in GMA patients. Future work should focus on enhancing the model by incorporating molecular biological data to increase its predictive accuracy and applicability.

Cost-effectiveness of pembrolizumab as an adjuvant treatment of renal cell carcinoma post-nephrectomy in Switzerland

Aims Pembrolizumab has demonstrated significantly prolonged disease-free survival and overall survival (OS) among adult patients post-nephrectomy who have an intermediate-high risk, high-risk, or M1 stage with no evidence of disease (M1 NED) renal cell carcinoma (RCC) with clear cell component. The aim of this study was to evaluate the cost-effectiveness of pembrolizumab for patients with RCC post-nephrectomy versus observation in Switzerland. Materials and methods A previously published Markov model was adapted for the Swiss setting to estimate the cost-effectiveness of adjuvant pembrolizumab versus observation from the Swiss statutory health insurance perspective. Transition probabilities between model states were estimated using survival curves from KEYNOTE-564 (data cut-off: June 14, 2021). Outcomes included costs (2022 Swiss francs [CHF]), quality-adjusted life-years (QALYs), and life-years (LYs), measured over a lifetime horizon. Costs included drug acquisition and administration for adjuvant and subsequent therapy. Both costs and effectiveness were discounted at 3.0% annually. Cost-effectiveness was evaluated at a hypothetical willingness-to-pay (WTP) threshold of CHF 100,000 Sensitivity was assessed through scenario analyses as well as deterministic and probabilistic sensitivity analyses. Results Over a lifetime horizon, the total incremental cost for pembrolizumab versus observation was CHF 59,089, providing incremental gains of 0.90 QALYs (1.07 LYs); the incremental cost-effectiveness ratio was CHF 65,299/QALY. Pembrolizumab was deemed cost-effective versus observation, with a 69.9% probability of cost-effectiveness. Limitations A more recent interim analysis data cut from KEYNOTE-564 with median follow up of 57.2 months has since been published; however, these were not available at the time of analysis. It would likely have minimal impact on transition probabilities from disease-free, and the current approach remains conservative for predicting OS for pembrolizumab. Conclusions As an adjuvant treatment of RCC post-nephrectomy, pembrolizumab was found to be cost-effective versus observation in Switzerland at a WTP threshold of CHF 100,000/QALY. Policy makers should consider pembrolizumab as an adjuvant treatment for patients with RCC post-nephrectomy when making decisions regarding resource allocation.

8080 Factors Affecting Survival of Lymph Node Positive Medullary Thyroid Cancer: A Population-Based Study From Surveillance, Epidemiology, and End Results (SEER) Program

Abstract Disclosure: M. Mortagy: None. A. Abdelhameed: None. M. Hegazy: None. Introduction: 50-70% of patients with MTC have positive lymph nodes. The Aim is to identify factors affecting survival of the lymph node positive MTC sub-population. Understanding these factors is important in treating these patients. Methods 1359 patients with lymph node positive MTC who were diagnosed with positive histology or cytology from 1975 to 2020 were extracted from SEER after removing duplicates. Survival analysis was performed, and Kaplan-Meier graph was produced. Univariate and multivariable Cox regression were performed, and respective hazard ratios (HR) were generated. Results: The cohort were 54% males with a median age of 55 years. Median survival: for the cohort was 163 months with survival of 91%, 80% and 74% at 1, 3, and 5 years respectively. Univariate Cox regression was statistically significant for age (HR 1.04), female sex (HR 0.64), T4 stage (HR 2.48), M1 stage (HR 5.43), bone metastasis (HR 4.74), brain metastasis (HR 17.1), liver metastasis (HR 5.41), lung metastasis (HR 5.97), distant lymph node metastasis (HR 6.00), number of positive lymph nodes (HR 1.008), lymph node ratio (HR 4.50), tumor size (HR 1.02), multifocal tumor (HR 0.69), total number of malignant tumors (HR 1.21), not performing total thyroidectomy (HR 6.35), chemotherapy (HR 3.85), radiotherapy after surgery (HR 1.67), beam radiotherapy (HR 2.20), systemic therapy after surgery (HR 0.67). Univariate Cox regression was not statistically significant for grade, treatment delay, total number of benign tumors, race/ethnicity, income, and living in rural areas. Multivariable cox regression was done after inclusion of all significant variables from univariate Cox regression. It was only significant for number of positive lymph nodes (HR 1.03), bone metastasis (HR 0.18), liver metastasis (HR 14.57), multifocal tumor (HR 3.49), total number of malignant tumors (HR 2.66), T4 stage (HR 3.57), M1 stage (HR 3.65), not performing total thyroidectomy (HR 352.43), tumor size (HR 1.03). Conclusion: Number of positive lymph nodes, T4 stage, M1 stage, presence of liver metastasis, presence of multifocal tumor, not performing total thyroidectomy and large tumor size lead to worse prognosis. Age, gender, chemotherapy, and lymph node ratio don’t affect survival. Future research is required to study this group of patients. Presentation: 6/2/2024

Survival in Thyroid Cancer in Sweden From 1999 To 2018.

Thyroid cancer (TC) is diagnosed in several histological types which differ in their clinical characteristics and survival. We aim to describe how they influence TC survival in Sweden. Cancer data were obtained from the Swedish cancer registry between years 1999 and 2018, and these were used to analyze relative survival. Relative survival for all TC improved when analyzed in 10-year periods, and female survival improved more than male survival. Female survival advantage appeared to be present also for specific histological types, although case numbers were low for rare types. Female 5-year relative survival for TC was 100% for follicular, 95.1% for oncocytic, 93.4% for papillary, 89.7% for medullary, and 6.1% for anaplastic cancer. Among the clinical TNM classes, only T4 and M1 stages were associated with decreased survival compared to T1-3 and M0. Anaplastic cancer presented most often at high T and M1 stages, in contrast to other TC. Curiously, the diagnostic age for anaplastic M1 patients was lower than that for M0 patients. Both anaplastic and medullary cancers did not show age-dependent increases in the probability of metastases, in contrast to the main histological types. This could indicate the presence of several types of anaplastic and medullary cancers. The poor survival for anaplastic TC is an extreme contrast to the excellent survival of differentiated TC. As less than 20% of anaplastic cancer patients survived one year, urgent diagnosis and initiation of treatment are important. Facilitated treatment pathways have been instituted in Denmark resulting in improved survival. Anaplastic cancer should be a target of a major research focus.

Role of CENPL, DARS2, and PAICS in determining the prognosis of patients with lung adenocarcinoma.

Non-small cell lung cancer (NSCLC) accounts for about 85% of lung cancers, and is the leading cause of tumor-related death. Lung adenocarcinoma (LUAD) is the most prevalent subtype of NSCLC. Although significant progress of LUAD treatment has been made under multimodal strategies, the prognosis of advanced LUAD is still poor due to recurrence and metastasis. There is still a lack of reliable markers to evaluate the LUAD prognosis. This study aims to explore novel biomarkers and construct a prognostic model to predict the prognosis of LUAD patients. The Genomic Data Commons-The Cancer Genome Atlas-Lung Adenocarcinoma (GDC-TCGA-LUAD) dataset was downloaded from the University of California, Santa Cruz (UCSC) Xena browser. The GSE72094 and GSE13213 datasets and corresponding clinical information were downloaded from the Gene Expression Omnibus (GEO) database. By analyzing these datasets using DESeq2 R package and Limma R package, differentially expressed genes (DEGs) were found. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to analyze possible enrichment pathways. A protein-protein interaction (PPI) network was constructed to explore possible relationship among DEGs by using the STRING database. A survival analysis was performed to identify reliable prognostic genes using the Kaplan-Meier method. A multi-omics analysis was performed using the Gene Set Cancer Analysis (GSCA). The Tumor Immune Estimation Score (TIMER) database was used to analyze the association between prognostic genes and immune infiltration. A Spearman correlation analysis was conducted to examine the correlation between prognostic genes and drug sensitivity. A multivariate Cox regression was used to identify independent prognostic factors. Next, a nomogram was constructed using the rms R package. Finally, the expressions of aspartyl-tRNA synthetase 2 (DARS2) and phosphoribosyl aminoimidazole carboxylase (PAICS) were detected using immunohistochemistry (IHC). We screened out 30 DEGs prior to functional enrichment and PPI network analysis revealing potential enrichment pathways and interactions of these DEGs. Then survival analysis revealed the CENPL, DARS2, and PAICS expression was negatively correlated with LUAD prognosis. Additionally, multi-omics analysis showed CENPL, DARS2, and PAICS expressions were significantly higher in LUAD tissues than normal tissues. CENPL, DARS2, and PAICS were all up-regulated in late stage and M1 stage. Correlation analysis indicated CENPL, DARS2, and PAICS may not be associated with activation or suppression of immune cells. Drug sensitivity analysis revealed many potentially effective drugs and small molecule compounds. Moreover, we successfully constructed a robust and stable nomogram by combining the DARS2 and PAICS expression with other clinicopathological variables. Finally, IHC results showed DARS2 and PAICS were significantly up-regulated in LUAD. The CENPL, DARS2, and PAICS expression was negatively correlated with LUAD prognosis. A prognostic model, which integrated DARS2, PAICS, and other clinicopathological variables, was able to effectively predict LUAD patients prognosis.

Clinicopathological and prognostic significance of stromal cell derived factor 2 in the patients with gastric cancer

BackgroundThe stromal cell derived factor 2 (SDF2) relates closely to the occurrence and development of several kind of cancers. There are few studies to investigate the clinicopathological and prognostic significance of SDF2 in gastric cancer (GC) patients.MethodsWe detected SDF2 expression in GC and normal gastric tissues using bioinformatics, western blot and immunohistochemistry. Furthermore, we tested the relationship between SDF2 expression and clinicopathological characteristics and prognosis of GC patients.ResultsBioinformatics, western blot and immunohistochemistry results showed that SDF2 expression in GC tissue was higher than that in normal gastric tissue (P < 0.01). SDF2 expression was associated with Borrmann classification III-IV (χ2 = 6.484, P = 0.011), depth of infiltration T3-T4 (χ2 = 9.140, P = 0.003), positive lymph node metastasis (χ2 = 24.945, P = 0.000) and TNM III-IV stage (χ2 = 9.945, P = 0.002) of GC patients. The Cox regression analysis indicated that distant metastasis M1 stage (HR = 6.026, 95% CI: 1.880-19.318, P = 0.003), TNM III-IV (HR = 1.833, 95% CI: 1.023–3.287, P = 0.042) and SDF2 high expression (HR = 2.091, 95% CI: 1.064–4.108, P = 0.032) were independent risk factors for OS of GC patients. Kaplan-Meier test showed that the OS of GC patients with SDF2 high expression was much poorer than that of GC patients with SDF2 low-expression (χ2 = 22.925, P = 0.000).ConclusionSDF2 expression is high in GC tissue and is correlated with Borrmann classification III-IV, tumor infiltration depth, positive lymph node metastasis and TNM III-IV stage of GC patients. GC patients with SDF2 high-expression have significantly poor OS.

Surgical management and outcomes of T4a papillary thyroid carcinoma: a single-centre study of 602 cases.

This study aimed to investigate the clinical characteristics and risk factors associated with the disease progression of T4a papillary thyroid carcinoma (PTC). In all, 602 patients (230 males; 372 females), aged 8-82 years, with T4a PTC who were admitted for initial surgery between April 2010 and September 2022 were retrospectively analysed. Tracheal invasion was observed in 271 (45.0%), oesophageal invasion in 190 (31.6%), recurrent laryngeal nerve (RLN) invasion in 516 (85.7%), and larynx invasion in 22 (3.7%) patients. The 5-year progression-free survival was 89.8%, and disease-specific survival was 96.0%, with a postoperative disease progression rate of 9.6% (54 patients) and mortality rate of 5.17% (29 patients). Disease recurrence was most likely to occur at the initial surgical site. Age ≥55 years, preoperative vocal cord paralysis, microvascular invasion, trachea invasion, and metastases to >5 cervical lymph nodes were independent risk factors for disease progression in patients with M0 stage. Male sex, preoperative vocal cord paralysis, microvascular invasion, specific pathological type, and laryngeal invasion were associated with an increased risk of disease progression for all T4a patients, while lobectomy, total thyroidectomy, tumour shaving on the RLN surface, total RLN resection, and absence of radioactive iodine therapy were not. Surgery was the primary treatment for patients with stage T4a PTC and most patients had a satisfactory prognosis. Surgeons should comprehensively evaluate each patient before deciding the surgical approach.

Impacts of 18F-FDG PET/CT Parameters on Differential Diagnosis and Outcome of Patients with Primary Invasive Mucinous and Lepidic Predominant Adenocarcinoma of the Lung.

The purpose of this study was to investigate whether 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) parameters have a role in differentiating invasive mucinous lung adenocarcinoma (IMA) from lepidic predominant lung adenocarcinoma (LPA). Additionally, we compared the 18F-FDG-PET/CT features between survivors and non-survivors. Tumors were divided into 2 groups according to CT appearance: Group 1: nodular-type tumor; group 2: mass- or pneumonic-type tumor. Unilateral and bilateral multifocal diseases were detected. Clinicopathological characteristics and PET/CT findings were compared between IMAs and LPAs, as well as between survivors and non-survivors. We included 43 patients with IMA and 14 with LPA. Tumor size (p=0.003), incidence of mass/pneumonic type (p=0.011), and bilateral lung involvement (p=0.049) were higher in IMAs than in LPAs. IMAs had more advanced T, M, and Tumor, Node, and Metastasis stages than in LPAs (p=0.048, p=0.049, and p=0.022, respectively). There was no statistically significant difference in maximum standardized uptake value (SUVmax) between the IMA and LPA (p=0.078). The SUV was significantly lower in the nodular group than in the mass/pneumonic-type group (p=0.0001). A total of 11 patients died, of whom SUVmax values were significantly higher in these patients (p=0.031). Male gender (p=0.0001), rate of stage III-IV (p=0.0001), T3-T4 (p=0.021), M1 stages (p=0.0001), multifocality (p=0.0001), and bilateral lung involvement (p=0.0001) were higher in non-survivor. Although CT images were useful for the differential diagnosis of LPAs and IMAs, SUVmax was not helpful for differentiation of these 2 groups. However, both 18F-FDG uptake and CT findings may play an important role in predicting prognosis in these patients.

Developing survival prediction models in colorectal cancer using epigenome-wide DNA methylation data from whole blood

While genome-wide association studies are valuable in identifying CRC survival predictors, the benefit of adding blood DNA methylation (blood-DNAm) to clinical features, including the TNM system, remains unclear. In a multi-site population-based patient cohort study of 2116 CRC patients with baseline blood-DNAm, we analyzed survival predictions using eXtreme Gradient Boosting with a 5-fold nested leave-sites-out cross-validation across four groups: traditional and comprehensive clinical features, blood-DNAm, and their combination. Model performance was assessed using time-dependent ROC curves and calibrations. During a median follow-up of 10.3 years, 1166 patients died. Although blood-DNAm-based predictive signatures achieved moderate performances, predictive signatures based on clinical features outperformed blood-DNAm signatures. The inclusion of blood-DNAm did not improve survival prediction over clinical features. M1 stage, age at blood collection, and N2 stage were the top contributors. Despite some prognostic value, incorporating blood DNA methylation did not enhance survival prediction of CRC patients beyond clinical features.

P-T evolution of HP migmatitic paragneiss from the Beni Bousera metamorphic unit (internal Rif, Northern Morocco) constrained by phase equilibria modelling and melt reintegration

ABSTRACT The high-pressure (HP) migmatitic paragneiss of the Beni Bousera metamorphic unit (BBMU) from the Beni Bousera Massif underwent granulite-facies metamorphism. They mainly consist of garnet, biotite, kyanite, sillimanite, cordierite, spinel, quartz, plagioclase, K-feldspar, rutile, ilmenite and graphite. These minerals form a sequence of metamorphic assemblages corresponding to five metamorphic events (M1, M2, M3, M4, and M5). The first three events correspond to a latest Carboniferous-earliest Permian metamorphic evolution, while the last two are retrograde and Alpine in age. The p-T conditions of these metamorphic events were estimated using pseudosection calculations in the MnNCKFMASTHO system. Following prograde stage conditions of 9.3–10.9 kbar and 630–665°C (M1 stage), the p-T evolution culminates in melting of the paragneiss which occurred mainly at HP conditions, within the kyanite stability field, at 11.8–14.2 kbar and 820–845°C (M2 pressure-peak); anatexis then continued at high to medium pressure (HMP), within the sillimanite stability field, at 9.9–11 Kbar and 840–860°C (M3 thermal-peak), accompanied by the production of very small proportions of melt. The prograde p-T segment of the inferred clockwise path is characterized by a pressurization related to a post-Variscan collisional event triggered by the closure of the Paleotethys Ocean, and is followed by the exhumation of the granulitic unit to mid-crustal depth, with slight coeval heating. The retrograde Alpine evolution is coeval with the final exhumation of the migmatitic paragneiss and underlying peridotites during back-arc extension related to the westward retreat of the Alpine subduction. It occurred under sub-solidus conditions from 9.5–10.7 kbar and 818–848°C (M4) to 4.9–5.85 kbar and 710–785°C (M5) and corresponds to a near-isothermal and strongly decompressive metamorphic evolution (ΔP ≈ 5 Kbar).

Study on the Structural Characteristics of Mesh Filter Cake in Drip Irrigation: Based on the Growth Stage of Filter Cake

Mesh filters are frequently employed in water-saving irrigation fields. Studies addressing the method of cake formation and the characteristics of the cake during the mesh filter’s growing phase are still missing. One-way and orthogonal experiments were carried out using mesh filters with 220 μm and 320 μm aperture sizes as the research objects, taking particle concentrations, inlet flow, and growth phases as experimental factors. According to the variation rule of seed pressure drop in the formation process of filter cake, the growth process of filter cake is divided into four stages, which are as follows: slow blockage first and second stages (M1, M2), fast blockage stage (M3), and filter cake filtration stage (M4). Moreover, the size distribution, porosity (ε), pore-to-particle ratio (KP), and median size (d50) of the filter cake were used to represent the structural characteristics. The results show that the growth of filter cake was a process that started with the filling of mesh pores by intercepted particles and progressed to the filling of large-particle skeleton pores by subsequently filtered particles. During this process, the proportion of intercepted particles gradually decreased, while the proportion of filtered particles increased incrementally, and the median size (d50) and porosity (ε) decreased. Meanwhile, the smaller the aperture size of the screen, the smaller the filter cake’s median size (d50) was, but the larger the pore-to-particle ratio (KP) was. As the flow rate increased, the porosity (ε) was augmented in the M1 and M2 stages; however, it decreased in the M3 and M4 stages. The concentration had a minor influence on the filter cake’s porosity. Lastly, the regression model for filter cake porosity under two aperture size conditions was established, based on factors such as flow rate, concentration, and growth stage. The coefficients of determination, R2, for the model were 90.33% and 80.73%, indicating a good fit.

Long term clinical outcomes of cervical cancer patients who were recommended surgery but did not undergo it: A SEER database study

BackgroundThis study analyzed the long-term clinical outcomes of cervical cancer patients recommended surgery but who did not undergo it using the Surveillance, Epidemiology, and End Results (SEER) database. The aim was to identify the subgroups with comparable overall survival (OS) and cancer-specific survival (CSS) through stratified analysis. MethodsCases of cervical cancer were retrieved from SEER database using SEER*Stat software. This included patients in the non-surgery group (recommended surgery but did not undergo it), and a reference surgery group. Propensity score matching balanced differences between the non-surgery and surgery groups. Stratified analysis and log-rank tests were used to identify subgroups within the non-surgery group with comparable OS and CSS to the surgery group. ResultsA total of 30,807 cervical cancer patients were included in the OS and CSS analysis. In the matched cohort (n = 1278), patients in the non-surgery group had significantly lower 5-year CSS (63.2 % vs. 80.1 %, P < 0.001) and 5-year OS (59.0 % vs. 78.0 %, P < 0.001). However, within the matched cohort, there was no statistically significant difference in OS and CSS between the non-surgery and surgery groups in subgroups diagnosed during 2010–2014 (P = 0.064, P = 0.182), 2015–2020 (P = 0.122, P = 0.518), T2 stage (P = 0.139, P = 0.052), T3 stage (P = 0.502, P = 0.317), or with distant metastasis (M1) (P = 0.411, P = 0.520). ConclusionPatients in the non-surgery group generally exhibited lower long-term clinical outcomes compared to those in the surgery group. However, with advancements in non-surgical treatment techniques, particularly notable in patients with T2, T3, and M1 stages, these differences are gradually diminishing.

Effectiveness of magnetic resonance imaging and spiral computed tomography in the staging and treatment prognosis of colorectal cancer.

Colorectal cancer (CRC) is a prevalent cancer type in clinical settings; its early signs can be difficult to detect, which often results in late-stage diagnoses in many patients. The early detection and diagnosis of CRC are crucial for improving treatment success and patient survival rates. Recently, imaging techniques have been hypothesized to be essential in managing CRC, with magnetic resonance imaging (MRI) and spiral computed tomography (SCT) playing a significant role in enhancing diagnostic and treatment approaches. To explore the effectiveness of MRI and SCT in the preoperative staging of CRC and the prognosis of laparoscopic treatment. Ninety-five individuals admitted to Zhongshan Hospital Xiamen University underwent MRI and SCT and were diagnosed with CRC. The precision of MRI and SCT for the presurgical classification of CRC was assessed, and pathological staging was used as a reference. Receiver operating characteristic curves were used to evaluate the diagnostic efficacy of blood volume, blood flow, time to peak, permeability surface, blood reflux constant, volume transfer constant, and extracellular extravascular space volume fraction on the prognosis of patients with CRC. Pathological biopsies confirmed the following CRC stages: 23, 23, 32, and 17 at T1, T2, T3, and T4, respectively. There were 39 cases at the N0 stage, 22 at N1, 34 at N2, 44 at M0 stage, and 51 at M1. Using pathological findings as the benchmark, the combined use of MRI and SCT for preoperative TNM staging in patients with CRC demonstrated superior sensitivity, specificity, and accuracy compared with either modality alone, with a statistically significant difference in accuracy (P < 0.05). Receiver operating characteristic curve analysis revealed the predictive values for laparoscopic treatment prognosis, as indicated by the areas under the curve for blood volume, blood flow, time to peak, and permeability surface, blood reflux constant, volume transfer constant, and extracellular extravascular space volume fraction were 0.750, 0.683, 0.772, 0.761, 0.709, 0.719, and 0.910, respectively. The corresponding sensitivity and specificity values were also obtained (P < 0.05). MRI with SCT is effective in the clinical diagnosis of patients with CRC and is worthy of clinical promotion.

Upregulation of the tumor suppressor gene LIN9 enhances tumorigenesis and predicts poor prognosis of lung adenocarcinoma

BackgroundLIN9, a gene associated with various cancers, is considered a tumor suppressor. However, the role of LIN9 in lung adenocarcinoma (LUAD) remains unknown. In this study, we aimed to assess the role of LIN9 in the occurrence and prognosis of LUAD. MethodsUsing three-tier HTSeq count RNA sequencing data from The Cancer Genome Atlas, we assessed LIN9 expression for the LUAD dataset using the DESeq2 R package and RT-qPCR experiments. Biological functions were assessed using gene set enrichment analysis (clusterProfiler and GOplot). The expression of LIN9 and the infiltration of immune cells were assessed by Single-sample gene set enrichment analysis. We conducted correlation study using clinical characteristics and receiver operating characteristic curve analysis. The predictive value of LIN9 was determined using univariate and multivariate Cox regression as well as Kaplan-Meier analysis. Additionally, functional studies were conducted to validate its role in the progression of LUAD. ResultsExpression of LIN9 was significantly elevated in LUAD, primarily influencing cell cycle, division, and signaling pathways. High LIN9 expression correlated positively with the infiltration of Th2 cells and inversely with that of plasmacytoid dendritic cells. Furthermore, LIN9 was associated with older age and advanced clinical stages, posing risks to overall, progression-free, and disease-specific survival. LIN9 served as a good diagnostic marker, particularly in females, patients aged over 65, and those with clinical N1–3 and M1 stages. Elevated LIN9 expression enhanced proliferation, migration, and invasion of LUAD cells. ConclusionHigh LIN9 expression potentially contributes to LUAD occurrence through cell cycle regulation and chromosomal modification. It promotes the malignant characteristics of LUAD cells and holds prognostic value for affected patients.

Efficacy of chemoradiotherapy in elderly patients with stage IV inoperable head and neck cancer.

This study aimed to compare the efficacy of chemoradiotherapy (CRT) with radiotherapy (RT) alone for elderly patients (≥ 65 years) with stage IV inoperable head and neck cancer (IV-HNC). Elderly patients diagnosed with inoperable IV-HNC from 2010 to 2015 were identified using the SEER database. Then, we performed a 1:1 propensity-score matched (PSM) analysis to reduce treatment selection bias, and the prognostic role of CRT was investigated using Kaplan-Meier analysis, log-rank test, and Cox proportional hazard models. The main outcome was overall survival (OS), and the secondary outcome was cancer-specific survival (CSS). A total of 3318 patients were enrolled, of whom 601 received RT alone and 2717 received CRT. Through PSM, 526 patients were successfully matched, and balances between the two treatment groups were reached. In the matched dataset, multivariable Cox analysis revealed that CRT was associated with better OS (HR = 0.580, P < 0.001) and CSS (HR = 0.586, P < 0.001). Meanwhile, subgroups of patients with IV-HNC (younger age, male sex, being married, black race, grade I-II, oral cavity site, T3-T4 stage, N0-N1 stage, M1 stage) were inclined to benefit more from CRT treatment. Furthermore, the survival benefit of CRT was more pronounced in patients aged 65 to 80 years, but was absent in patients aged 80 years or older. This study indicated that CRT resulted in better survival than RT alone in elderly patients with inoperable IV-HNC, especially for those subpopulations that benefit more from CRT treatment.

Characterization of the Hoof Bacterial Communities of Active Digital Dermatitis Lesions in Feedlot Cattle.

Digital dermatitis (DD) is a costly hoof infection, causing lameness and pain in feedlot cattle. DD lesions can develop nonlinearly through a series of clinical stages, which can be classified by Dopfer's M-stage scoring system. This widely adopted lesion scoring system recognizes five DD stages, where M1 (early lesion), M2 (acute ulcerative lesion), and M4.1 (chronic proliferative lesion with new developing lesion) are considered active but separate stages of the disease. This study assessed the skin surface microbiota of the active DD lesions of feedlot cattle. The DD lesions from three commercial feedlots were swabbed and then scored according to Dopfer's M-stage scoring system. Swab samples were collected from 12 M2- and 15 M4.1-stage lesions. A total of 21 control swab samples from healthy contralateral feet (DD control) were classified as stage M0. An additional six skin swabs (M0) were collected from completely healthy (CH control) cattle with no lesions. The bacterial communities of active DD lesions (M2 and M4.1) and healthy skin (M0) were profiled using 16S amplicon sequencing. Diversity analyses showed that the hoof bacterial communities of M2 and M4.1 lesions were each distinct from those of M0 skin. However, the bacterial communities between the two active lesion stages were not different from each other. A significant increase in the relative abundance of Spirochaetota and Fusobacteriota and an overall decrease in bacterial diversity contributed to the altered bacterial communities in M2 and M4.1 lesions compared to those of healthy skin (M0). Although stages M2 and M4.1 are considered clinically different stages, the lesion-associated bacterial community is similar between the two active stages.

Treatments and prognostic outcomes of combined hepatocellular-cholangiocarcinoma with distant metastasis: an analysis based on SEER data.

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare liver cancer with a poor prognosis, often diagnosed at an advanced stage. The management of cHCC-CCA with distant metastasis remains challenging, and prognostic factors are not well-defined. This study aimed to investigate prognostic factors and treatment outcomes for cHCC-CCA patients with distant metastasis. Retrospective analysis was conducted using data from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database. Patients with distant metastasis [stage M1, according to the American Joint Committee on Cancer (AJCC) 7th edition] between January 2010 and December 2020 were included. Their characteristics, clinical profiles, and prognostic information were evaluated. Cox multifactorial survival analysis and Kaplan-Meier survival curves were used for statistical analysis. A total of 130 patients were included, with 78 (60%) receiving chemotherapy. Cox multivariate survival analysis revealed worse prognosis for Black individuals compared to White individuals (P<0.05). The median overall survival was 2 months for Black patients and 5 months for White patients. Chemotherapy significantly improved patient prognosis (P<0.05), while lung metastasis emerged as an independent risk factor (P<0.05). Kaplan-Meier survival curves confirmed the impact of lung metastasis and chemotherapy on overall survival. Patients with lung metastasis had lower survival rates (P<0.05), and those receiving chemotherapy had higher survival rates (P<0.05). Subgroup analysis based on age showed lower survival rates in patients aged 75 years or older compared to those below 75 years. Chemotherapy showed significant beneficial effects on the prognosis of patients below 75 years old, but no significant difference was observed in patients aged 75 years or above. Chemotherapy improves the prognosis of cHCC-CCA patients with distant metastasis, especially for those under 75 years old. Black race and lung metastasis are poor prognostic factors.

Different prognosis in cutaneous early-onset and late-onset Merkel cell carcinoma: a population-based retrospective study.

Merkel cell carcinoma (MCC) is a rare and highly aggressive form of skin cancer. However, there is limited research on the clinicopathological features of early-onset MCC (EOMCC) and the differences between EOMCC and late-onset MCC (LOMCC). Our objective was to evaluate the clinicopathological features and cancer-specific survival (CSS) of EOMCC. Our cohort study analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2018, to December 31, 2020. Data from 1941 patients who were diagnosed with primary cutaneous MCC were included. We then divided the patients with MCC into two groups: those with EOMCC (526 patients) and those with LOMCC (1415 patients). CSS is used as the primary outcome. The EOMCC group exhibited trends toward advanced tumor progression, an expanded surgical scope, increased lymph node retrieval, intensified radiotherapy, greater utilization of systemic therapy, and a better prognosis. Multivariate analysis revealed that LOMCC (HR 3.305 [2.002-5.456], P < 0.001), advanced T stage (HR 1.430 [1.139-1.797], P = 0.002), advanced N stage (HR 1.522 [1.221-1.897], P < 0.001), M1 stage (HR 2.587 [1.480-4.521], P < 0.001), and radiation (HR 0.586 [0.410-0.837], P = 0.003) were significantly associated with CSS. Among these factors, EOMCC/LOMCC was most strongly associated with CSS, indicating that LOMCC is an independent risk factor for CSS. Interestingly, we found that regional EOMCC and localized or in situ LOMCC had almost completely overlapping survival curves (Plog-rank = 0.620). Additionally, we observed that the TNM staging + age model was a more accurate predictor of CSS among MCC patients than using TNM staging alone. We found that EOMCC has distinct clinicopathological features compared to LOMCC. EOMCC is associated with better CSS. The combination of TNM staging and age was more accurate for predicting patient outcomes than TNM staging alone.

Recurrence patterns following nephrectomy for renal cell carcinoma in a Danish nationwide cohort.

This study aimed to characterize the demographic and clinical features of patients with renal cell carcinoma (RCC) post-surgery for localized or locally advanced disease in a national Danish cohort, with a specific focus on describing recurrence patterns in a subgroup aligned with the adjuvant KEYNOTE-564 trial classification. This was a retrospective analysis of the Danish Renal Cancer (DaRenCa) database. Eligible subjects were individuals with an RCC diagnosis between January 2014 and December 2017 who subsequently underwent radical or partial nephrectomy. Variables of interest were demographic and clinical characteristics, rates and sites of recurrence. Recurrence rates were also assessed in a subpopulation stratified using the risk classifications of the KEYNOTE-564 trial. A total of 2164 RCC patients were identified. Most patients (84.8%) had non-metastatic RCC (stage M0). A recurrence was observed in 250 of the M0 patients (13.6%). Patients with a recurrence were older, male, had a higher tumour stage, had undergone radical nephrectomy and had a higher Leibovich score. The majority (74.8%) of M0 patients had recurrence at distant metastatic sites. A total of 392 patients were stratified by the KEYNOTE-564 risk classification: 335 intermediate-high risk, 17 high risk and 40 M1 NED (metastatic with no evidence of disease). Recurrence was observed in 37.0%, 88.2% and 27.5% of these risk groups, respectively. This study elucidates the rates and determinants of post-surgical RCC recurrence in Denmark, underscoring the potential of adjuvant immunotherapy in refining therapeutic strategies, identifying suitable beneficiaries and minimizing overtreatment risks in RCC care.

Decade-long insights into transperineal prostate biopsy in a west China population: Temporal trend, targeted and repeat biopsies, and pathological characterization.

e17004 Background: Despite advances in prostate cancer (PCa) detection, the need for improving diagnostics and in-depth assessment of the latest prostate biopsy (PBx) techniques through extensive, longitudinal studies remains critical. Methods: Data from 10,378 PBx involving 10,038 patients were retrospectively examined. We detailed the yearly changes in PBx numbers and patient diagnoses, the real-world efficacy of PI-RADS scoring, MRI-targeted biopsy (MRI-TBx), and repeat PBx. We also outlined the detection rates and the clinical profiles of non-adenocarcinoma (non-AC) PCa. Results: A consistent annual increase in PBx was witnessed, with the positive rate climbing to approximately 55%. There was a gradual decline in median age, PSA levels, and M1 stage proportion among PCa patients, suggesting an earlier diagnosis trend. However, compared to Western populations, our center's patients had a significantly higher incidence of M1 stage (34% vs. 6%, P&lt;0.001) and, within the M0 category, presented with older age and elevated baseline PSA levels. Integrating MRI-TBx into the 12-core systematic biopsy (SBx) led to a numerical improvement in PCa detection and enhanced ISUP grading accuracy. Merging MRI-TBx with a 6-core SBx achieved a median clinically significant PCa (csPCa) detection rate of 39.76% in men with PSA&lt;20ng/mL, similar to that of MRI-TBx with a 12-core SBx (40.36%). Furthermore, we identified 1,455 men with non-AC PCa, occurring less in localized cases (about 15%) but more in metastatic cases (over 50%), and exhibiting more aggressive characteristics compared to adenocarcinoma-only cases. Besides, among the 305 individuals undergoing repeat PBx, 62 csPCa cases were identified, all of which exhibited lower positive cores, ISUP grading, and M1 stage incidence than men diagnosed by initial PBx. Conclusions: Analyzing a decade's worth of PBx data from one of the largest Asian cohorts offered pivotal insights into the evolving epidemiology and clinical profiles of PBx, which are essential for shaping future diagnostic approaches for PCa.