Pathological Subtypes Research Articles

Analysis of lipogenic and metabolic subtypes and survival outcome in patients with pancreatic adenocarcinoma.

775 Background: Delayed diagnosis and rapid progression are major drivers of poor survival outcomes for Pancreatic Ductal Adenocarcinoma (PDAC). In previous studies, molecular profiling in tumor tissue has identified Cholesterogenic, Classical, or Exocrine-Like pathological subtypes associated with improved prognosis. Herein, in a clinical trial called Project Survival, we molecularly and clinically characterized a prospective PDAC biomarker cohort. This multicenter (n=6) clinical trial (NCT 02781012) of PDAC combined with high-fidelity longitudinal phenotypic characterization and multi-omic profiling was utilized to identify biomarkers with diagnostic and therapeutic utility. The study included assessment of plasma, serum, buffy coat, urine, saliva, and tumor tissue samples and followed 269 PDAC subjects for up to 7 years (Median survival was 700 days, with IQR of 822 days). Methods: We assessed plasma samples to identify circulating biomarkers using proteomics, metabolomics, and lipidomics profiling. Multi-omic comparison of patients with Overall Survival (OS) above the 75th percentile (improved survival) against those with OS below the 25th percentile (poor survival) was performed. Results: We identified distinct panels of proteins, metabolites, and lipids that were associated with patient survival outcomes. Protein biomarkers that were increased in improved survival outcomes were associated with cholesterol metabolism (7/14, p-value = 0.00085) and glycolysis/gluconeogenesis (5/12, p-value = 0.00089), however, protein markers associated with immune surveillance and inflammation were associated with poorer survival. For metabolite biomarkers, 19 metabolites were increased in poorer survivors of which 13/19 were carnitine metabolites, and 42 metabolites were increased in patients with improved survival. Interestingly, only two lipid molecular species of the diacylglyceride family were increased in patients with poorer survival. Conclusions: Project Survival, a prospective biomarker-driven clinical trial identified distinct metabolic and molecular subtypes of patients which characterize survival outcome in PDAC. These subtypes go beyond tumor genomic characterization and align with distinct cholesterogenic and glucogenic phenotypes associated with survival outcomes, which can potentially be leveraged for therapeutic intervention strategies.

Molecular testing stratifies the risk of structural recurrence in high risk differentiated thyroid cancer: a retrospective cohort study

BackgroundHigh-risk differentiated thyroid cancer in 2015 American Thyroid Association risk stratification system (ATA-RSS) exhibits a significantly increased probability of recurrence and poor outcomes. This study aimed to investigate the molecular profiles of high-risk differentiated thyroid cancer and to assess the role of molecular testing in enhancing prognostic risk stratification.MethodsIn a single-center study conducted at Fujian Cancer Hospital, Fujian Province, China, a consecutive cohort of differentiated thyroid cancer patients identified as high-risk under 2015 ATA-RSS criteria were retrospectively assessed, spanning from November 1, 2019, to March 31, 2022. Molecular characterize groups were conducted using an 18-gene next-generation sequencing assay. Patients harboring mutations in the TERT promoter, TP53, or PIK3CA genes were categorized as the high molecular risk group, while all others were assigned to the non-high molecular risk group.ResultsAmong the 108 cases, 32 (29.6%) fell into the high molecular risk group, characterized by a significantly older mean age (57.8 vs. 42.6 years, p < 0.001), larger tumor size (3.1 cm vs. 2.0 cm, p = 0.003), a higher incidence of aggressive pathological subtypes (43.8% vs. 7.9%, p < 0.001), and an increased occurrence of distant metastasis (34.4% vs. 7.9%, p = 0.001). Over a median follow-up period of 32.5 months, this high-risk group demonstrated an elevated risk of local recurrence (32.1% vs. 9.5%, HR: 3.18, 95% CI: 1.15-8.78) and metachronous distant metastasis (38.1% vs. 2.9%, HR: 12.54, 95% CI: 2.60-60.41). Multivariate COX regression analysis confirmed that molecular characterize groups (HR: 5.77, 95% CI: 2.18-15.23, p < 0.001) and tumor size (HR: 1.32, 95% CI: 1.00-1.74, p = 0.047) independently predicted recurrence-free survival.ConclusionATA-RSS high-risk differentiated thyroid cancer often presents with late-hit genetic alterations, which are strongly associated with increased likelihood of structural recurrence. Molecular testing offers a precise approach to recurrence risk stratification in high-risk cases, enabling personalized follow-up and treatment strategies tailored to the specific prognostic profile.

Clinical significance of molecular classification and hereditary phenotypic characteristics in endometrial carcinoma

Objective: To analyze the clinical significance of molecular classification and hereditary phenotype in endometrial carcinoma (EC) based on high throughput sequencing (NGS). Methods: 97 EC samples were collected retrospectively from December 2019 to October 2022 in China-Japan Friendship Hospital. NGS technique was used to analyze the molecular classification, POLE hypermutation, microsatellite high Instability/mismatch repair dysfunction (MSI-H/MMRd), P53 protein abnormality (P53 abn), and non-specific molecular profile (NSMP). Lynch syndrome related genes and BRCA1/2 genes were detected by NGS and their genetic characteristics were analyzed. Results: Of the 97 EC cases, 77 were endometrial adenocarcinoma and 20 were other pathological subtypes. The proportions of the four molecular subtypes were 9.3% (9/97) POLE hypermutation, 16.5% (16/97) MSI-H, 17.5% (17/97) P53 abn and 56.7% (55/97) NSMP, respectively. There were significant differences in age, histological type, lymph node metastasis, pathological stage and other parameters among the four molecular types (P＜0.05). 8.2% (8/97) were multiple molecular typing and four multiple molecular typings detected, including POLEmut-MSI-H, POLEmut-P53abn, MSI-H-P53abn, P53abn-P53abn, which accounted for 1.0% (1/97), 3.1% (3/97), 1.0% (1/97) and 3.1% (3/97), respectively. The consistent rate of MSI-H and MMR protein expression was 92.9% (Kappa=0.818, P＜0.001). The coincidence rate between TP53 gene sequencing and P53 protein expression was 88.9% (Kappa=0.661, P＜0.001). In MSI-H type, 25.0% (4/16) were diagnosed as Lynch syndrome, and 75.0% (12/16) were diagnosed as Lynch like syndrome. 7.2% (7/97) BRCA2 somatic variation was detected, while BRCA1/2 germline variation was not detected in 97 cases. Conclusions: EC molecular classification has feasibility and clinical value. High throughput sequencing can detect low frequency mutations of TP53 gene, suggesting that it can provide more accurate molecular information and more accurate molecular typing effect. It is suggested to further detect Lynch syndrome related genes in patients with MSI-H, so as to carry out genetic management for patients and their families and achieve better therapeutic effect.

Analysis of survival and prognostic factors in appendix adenocarcinoma and mucinous carcinoma.

This study aimed to compare mucinous carcinoma and adenocarcinoma of the appendix in terms of survival and investigate the risk factors influencing survival. The data for this study were retrieved from the SEER database (SEER Research Plus 17 registries). Patients diagnosed with appendix cancer between 2004 and 2019 were included. Demographic data, such as age, gender, marital status, and year of diagnosis, along with oncological variables like stage, surgery, chemotherapy, radiotherapy, and survival time, were extracted from the SEER database. Pathological subtypes were classified as adenocarcinoma (AC) and mucinous adenocarcinoma (MAC) based on the College of American Pathologists guidelines. Patients with other pathological subtypes or missing data were excluded from the study. This study included 4524 patients, with 2118 (46.8%) classified as AC and 2406 (53.2%) as MAC. There was no significant difference in mean age between AC and MAC groups (63.22 ± 14.30 vs. 59.46 ± 14.07, p = 0.483). AC was more common in males, while MAC was more prevalent in females (46.8% vs. 53.2%; 55.6% vs. 44.4%, p < 0.001, respectively). Married status was high in both groups (p = 0.001). While no difference was found in white race distribution, the black race was more prevalent in the AC group (57.1% vs. 42.9%, p < 0.001). Grade 1 tumors were more frequent in the AC group, whereas Grades 2 and 3 were more common in the MAC group (p < 0.001). Stages 1, 2, and 3 were more prevalent in the AC group, while the majority of MAC cases were at Stage 4. Surgery rates were higher in the AC group (98.6% vs. 96.4%, p < 0.001). Chemotherapy was used more frequently in the MAC group (50.9% vs. 40.6%, p < 0.001), while radiotherapy rates were similar in both groups (p = 0.498). The mean follow-up period was 55.70 ± 47.2months. Five- and ten-year survival rates for the MAC group were 64.4% and 50.2%, respectively, higher than the AC group's rates of 54.2% and 39.7% (p < 0.001). The overall risk of mortality was 1.4 times higher in the AC group compared to the MAC group (p < 0.001, HR: 1.377 [CI 95% 1.259-1.507]). While adenocarcinomas and mucinous adenocarcinomas have similar incidences, non-metastatic adenocarcinomas were more frequently observed. In contrast, mucinous adenocarcinomas often exhibited distant metastases. Nevertheless, the survival rate was higher in mucinous adenocarcinomas.

Safety and Efficacy of Anlotinib-based Regimen in Patients with Unresectable or Metastatic Bone and Soft-tissue Sarcomas: A Retrospective Institutional Study.

Anlotinib has demonstrated durable clinical benefits in patients with unresectable or metastatic bone and soft-tissue sarcomas. 92 patients treated with chemotherapy combined with or without anlotinib were collected and analyzed. The objective response rate (ORR) and disease control rate (DCR) were analyzed. Long-term survival was assessed using the Kaplan-Meier method, including median progression-free survival (mPFS) and overall survival (mOS). Liposarcoma, synovial sarcoma, and rhabdomyosarcoma were the primary pathological subtypes of the 92 patients. The median age was 46 (range, 11-75) years. The ORR and DCR of the anlotinib-chemotherapy combination used as first-line therapy were 31.9% and 85.1%, respectively. However, the ORR and DCR were only 6.7% and 57.8% in the chemotherapy alone, respectively. Compared with the chemotherapy group, improvements were observed in the mPFS and mOS with anlotinib-based regimen (mPFS, 8.3 vs. 3.0 months; mOS, 59.0 vs. 22.0 months). Anlotinib-associated adverse events were well tolerated and mainly occurred in grades I and II. New anlotinib-related adverse reactions were not noted. Anlotinib-based regimen as a first-line therapy showed a positive effect on the treatment of unresectable or metastatic BSTSs. The anlotinib-associated adverse events were minor and well tolerated.

The benefits of contrast-enhanced ultrasound in the differential diagnosis of suspicious breast lesions.

Contrast-enhanced ultrasound (CEUS) shows potential for the differential diagnosis of breast lesions in general, but its effectiveness remains unclear for the differential diagnosis of lesions highly suspicious for breast cancers. This study aimed to evaluate the diagnostic value of CEUS in differentiating pathological subtypes of suspicious breast lesions defined as category 4 of US-BI-RADS. The dataset of 150 breast lesions was prospectively collected from 150 patients who underwent routine ultrasound and CEUS examination and were highly suspected of having breast cancers. All lesions were pathologically confirmed by US-guided needle biopsy and surgery. The qualitative features and the quantitative parameters of CEUS of these breast lesions were analyzed. The CEUS and biopsy examinations were performed after informed consent. In the qualitative features, crab clam-like enhancement, the presence of more than two enhanced vessels within lesions, and surrounding enriched vessels inserting into lesions were able to differentiate atypical fibroadenomas (FIB) and mass-like non-puerperal mastitis (NPM) from invasive ductal carcinomas (IDC) and ductal carcinomas in situ (DCIS) (p < 0.05). The enlarged scope, irregular shape, and perfusion deficiency were valuable to the differential diagnosis of FIB from the others (p < 0.05). In the four quantitative parameters of CEUS, only the peak intensity (IMAX) contributed to the differential diagnosis between malignant and benign tumors (p < 0.05, ROCAUC: 0.61, sensitivity: 60.4% and specificity: 65.9%, accuracy: 62.1%). However, IMAX did not show any difference in the paired comparison of IDC, DCIS, FIB, and NPM (p > 0.05). The logistic regression analysis results showed that heterogeneous perfusion, crab clam-like enhancement, and partial_ IMAX were independent risk factors for benign and malignant breast lesions (p < 0.05). The area under a receiver operating characteristic of the integrated model was 0.89. In the diagnosis of benign and malignant pathological subtypes of breast lesions, independent risk factors and integrated models had no statistical significance in the diagnosis of IDC and DCISs, FIB, and NPM (p > 0.05). Some qualitative risk features of CEUS can distinguish malignant breast lesions from NPM and atypical FIB with a high score of US-BI-RADS, aiding physicians to reduce the misdiagnosis of suspicious breast lesions in clinical practice.

Post-marketing surveillance data for avelumab + axitinib treatment in patients with advanced renal cell carcinoma in Japan: Subgroup analyses by pathological classification.

Clinical trials have demonstrated the efficacy and safety of avelumab + axitinib in patients with advanced clear cell renal cell carcinoma (ccRCC). However, information is limited regarding the activity of avelumab + axitinib in patients with non-clear cell RCC (nccRCC). In Japan, post-marketing surveillance (PMS) of patients with RCC receiving avelumab + axitinib treatment in general clinical practice was undertaken. We report ad hoc analyses of PMS data according to RCC pathological classification. Of 328 patients with RCC who received ≥1 dose of avelumab and were enrolled between December 2019 and May 2021, 271 (82.6%) had ccRCC, 22 (6.7%) had nccRCC, and 35 (10.7%) had missing or unknown RCC pathology. Among patients with nccRCC, pathological subtypes were papillary in 12 (3.7%), translocation in 3 (0.9%), acquired cystic disease associated in 3 (0.9%), chromophobe in 2 (0.6%), mucinous tubular and spindle cell in 1 (0.3%), and Bellini duct in 1 (0.3%). Among patients with ccRCC or nccRCC, any-grade adverse drug reactions of safety specifications occurred in 140 (51.7%) and 15 (68.2%), and of grade ≥3 in 48 (17.7%) and 6 (27.3%), respectively. The objective response rate in patients with ccRCC or nccRCC was 36.9% and 22.7%, respectively; in patients with papillary tumors, it was 33.3%. Median overall survival was not reached in patients with ccRCC or nccRCC, and 12-month overall survival rates were 86.8% and 76.7%, respectively. Overall, subgroup analyses of PMS data suggest that avelumab + axitinib improved clinical outcomes in nccRCC in addition to ccRCC.

Primary head and neck lymphoid neoplasms in adolescents and young adults: demographics, distribution and survival outcomes.

Primary head and neck lymphoid neoplasms(PHNLN) are described as a series of lymphoid system-derived neoplasms which originally arising from head and neck region. Our study is aimed to present a panoramic view of PHNLN among adolescent and young adult(AYA) patients aged from 15 to 39 years-old. The individual patient information was obtained from Surveillance, Epidemiology and End Results(SEER) database. Male patients outnumbered female patients in most pathological subtypes, with noticeable male predilection observed in Burkitt lymphoma and diffuse large B-cell lymphoma(DLBCL). Classical Hodgkin lymphoma(CHL) accounted for 92.23% of Hodgkin lymphoma. Mature B-cell neoplasms constituted the majority of non-Hodgkin lymphoma(NHL). DLBCL was the most common pathological subtype, followed by follicular lymphoma(FL). Tonsil, salivary glands (especially parotid gland) and nasal cavity were the most three frequent extranodal organs involved. Patients with extranodal involvement exhibited worse prognosis compared to those with lymph node confinement. Patients who suffered from precursor NHL and mature T/NK-cell NHL exhibited prolonged disease-specific survival compared to those with HL, PCN and mature B-cell NHL. AYA patients with absence of other SPM showed dramatic lower risk of death than those with occurrence of SPM. Patients with HL had a favourable survival advantage over those with mature B-cell NHL. Patients with precursor NHL and mature T/NK-cell NHL were at remarkable higher risk of death than those with mature B-cell NHL. Our study elucidated the demographics, distribution of anatomic sites and pathological subtypes, and survival outcomes of PHNLN among AYA population, enhancing comprehension of this rare sort of cancer entities.

Cortically Based Brain Tumors in Children: A Decision-Tree Approach in the Radiology Reading Room.

Cortically based brain tumors in children constitute a unique set of tumors with variably aggressive biologic behavior. Because radiologists play an integral role on the multidisciplinary medical team, a clinically useful and easy-to-follow flow chart for the differential diagnoses of these complex brain tumors is essential. This proposed algorithm tree provides the latest insights into the typical imaging characteristics and epidemiologic data that differentiate the tumor entities, taking into perspective the 2021 World Health Organization's classification and highlighting classic as well as newly identified pathologic subtypes by using current molecular understanding.

Correlation between [18F]-FDG PET/CT findings and pathological subtypes of lung adenocarcinoma presenting as ground-glass opacity.

The aim of this study is to analyze the correlation between [18F]-FDG PET/CT (positron emission tomography/computed tomography) findings and pathological subtypes of lung adenocarcinoma with ground-glass opacity (GGO). 88 patients were included in this study, which underwent [18F]-FDG PET/CT and were finally diagnosed with lung adenocarcinoma. A total of 90 GGO lesions were analyzed. The size and SUVmax of all lesions were measured, the proportion of solid components of GGO in lesions was calculated, and quantitative classification was performed. The above GGO lesions were divided into three groups based on the 2011 IASLC/ATS/ERS lung adenocarcinoma pathological classification, namely good prognosis group, relatively good prognosis group and poor prognosis group. Chi-square test, independent sample t test, and analysis of variance were used for statistical analysis. There was a negative correlation between the SUVmax and quantitative classification value (r = -0.638, P < 0.001). Atypical adenomatous hyperplasia (AAH), acinar predominant adenocarcinoma (APA), lepidic predominant adenocarcinoma (LPA), papillary predominant adenocarcinoma (PPA), and solid predominant adenocarcinoma (SPA) had significant differences in GGO lesion size, SUVmax, and quantitative classification value (F = 3.849, P = 0.019; F = 27.420, P < 0.001; F = 4.353, P = 0.002). There were significant differences in GGO lesion size, SUVmax, and quantitative classification value among the good prognosis group, relatively good prognosis group, and poor prognosis group (F = 5.626, P = 0.011; F = 37.587, P < 0.001; F = 5.119, P = 0.008). GGO lesion size, SUVmax, and quantitative classification value are correlated with different pathological subtypes and can be used toevaluate the prognosis of lung adenocarcinoma with GGO.

Longitudinal Testing of Circulating Tumor DNA in Patients With Metastatic Renal Cell Carcinoma.

Tumor-informed circulating tumor DNA (ctDNA) has shown promise as a biomarker for treatment response monitoring (TRM) in a variety of tumor types, with the potential to improve clinical outcomes. We evaluated ctDNA status and dynamics during surveillance and as part of TRM with clinical outcomes in both patients with clear cell renal cell carcinoma (ccRCC) and non-clear cell renal cell carcinoma (nccRCC) treated with standard-of-care immunotherapy or targeted therapy regimens. This was a multicenter retrospective analysis of real-world data obtained from commercial ctDNA testing (Signatera, Natera, Inc) in patients with metastatic RCC. Clinical data were collected on International Metastatic RCC Database Consortium (IMDC) risk category, pathologic subtype, and grade. The cohort comprised 92 patients (490 plasma samples) including both clear cell and non-clear cell histological subtypes (ccRCC: 79.3%; nccRCC: 14.1%; unclassified: 6.5%). Most of the patients belonged to the IMDC intermediate-risk category (75%, 69/92). Median follow-up was 10 months (range, 4.2-25.8). ctDNA dynamics were assessed in 56 patients on treatment, and ctDNA status was analyzed in the surveillance cohort (n = 32 patients). Serial ctDNA negativity or clearance correlated with improved progression-free survival (PFS) compared with those who became or were persistently ctDNA positive on therapy (hazard ratio [HR], 3.2; P = .012). In the surveillance cohort, patients with positive ctDNA longitudinally experienced significantly inferior PFS (HR, 18; P = .00026) compared with those who were serially negative. Collectively, we show that serial ctDNA monitoring provides prognostic information for patients undergoing treatment or surveillance, and our findings demonstrate high concordance between ctDNA status/dynamics and subsequent clinical outcomes.

Radiomic signatures of brain metastases on MRI: utility in predicting pathological subtypes of lung cancer.

The pathological sub-classification of lung cancer is crucial in diagnosis, treatment and prognosis for patients. Quick and timely identification of pathological subtypes from imaging examinations rather than histological tests could help guiding therapeutic strategies. The aim of the study is to construct a non-invasive radiomics-based model for predicting the subtypes of lung cancer on brain metastases (BMs) from multiple magnetic resonance imaging (MRI) sequences. One hundred and sixty-one patients of primary lung cancer with synchronous BMs [121 with adenocarcinoma (AD); 40 with small cell lung carcinoma (SCLC)] were enrolled in the study (129 and 32 in the training set and validation set). A total of 960 radiomics features were extracted from multiple MRI sequences [fluid attenuated inversion recovery (FLAIR), diffusion weighted imaging (DWI), contrast-enhanced T1 weighted imaging (CE-T1WI) and contrast-enhanced susceptibility weighted imaging (CE-SWI)] and four clinical features were recorded. Forty-one key features were selected by the least absolute shrinkage selection operator (LASSO). The machine learning (ML) models for predicting AD and SCLC with radiomics features alone and with radiomics features plus clinical features were constructed using classifiers of logistic regression (LR), random forest (RF), support vector machine (SVM) and extreme gradient boosting (XGBoost). The prediction performance of models was evaluated by accuracy (ACC), sensitivity (SEN), specificity (SPE), F1 score and area under the curves (AUC). The AUCs of LR, RF, SVM and XGBoost models were 0.8177 vs. 0.7604, 0.8177 vs. 0.7839, 0.4792 vs. 0.8594 and 0.9062 vs. 0.8750, respectively, when using radiomics features alone and radiomics features plus clinical features. In the best-performing model using XGBoost, combination of conventional MRI sequences and CE-SWI had better sub-classification performance than conventional MRI sequences. Radiomics of BMs from multiple MRI sequences provides high discriminatory performance in predicting AD and SCLC using classifiers of LR, RF and XGBoost, and can serve as a potential useful tool to non-invasively distinguish pathological subtypes of lung cancer.

Diagnostic accuracy of folate receptor-positive circulating tumor cells in differentiating between benign and malignant pulmonary nodules.

Currently, traditional blood biomarkers such as neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCCA) etc. are mostly elevated in the late stage of tumour, and patients have already lost the chance of tumour eradication when the relevant indexes are found to be elevated. Therefore, there is a need for blood biomarkers with higher sensitivity, better specificity, and better accessibility. Folate receptor-positive circulating tumor cells (FR+CTCs) may have diagnostic value in lung cancer. Nevertheless, there is a scarcity of research exploring the efficacy of FR+CTCs in screening pulmonary nodules for lung cancer. The aims of this study were to differentiate between lung cancer and benign pulmonary nodules using FR+CTCs in conjunction with blood markers and to develop a composite diagnostic model for pulmonary nodules. Based on the inclusion and exclusion guidelines, we retrospectively analysed 1,135 patients with pulmonary nodules who underwent tissue biopsy or surgical resection after FR+CTC testing, assessed the histopathological findings by a specialised pathologist, and collected and compared demographic characteristics, blood markers, imaging and pathological parameters in malignant and benign patients. The random forest model was used to screen for indicators and to establish a composite index of blood biomarkers. The performance of single factors or the integrated model were estimated by applying receiver operating characteristic (ROC) analysis. A total of 612 patients were included in the lung cancer group, predominantly presenting with stage I adenocarcinomas (n=458). The median age was 54 years, and 43.1% of the patients were male. In comparison, 523 patients were included in the benign pulmonary nodules group, with a median age of 53 years and 46.8% male. No significant differences were identified between the two groups with regard to gender or age (P>0.05). The level of FR+CTCs in the lung cancer group was significantly higher than that in the benign nodule group (P<0.001). The white blood cell (WBC) and cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) levels were significantly higher in the lung cancer group than in the benign nodule group (P<0.001 and P=0.01, respectively). FR+CTC level was associated with the pathological subtype (P=0.02), WBC (P<0.001), and lactate dehydrogenase (LDH) level (P=0.01). In both groups, the FR+CTC level was higher in the single-nodule group than in the multiple-nodule group (P=0.002 and P=0.040, respectively). The diagnostic sensitivity and specificity of FR+CTCs for lung cancer at a cutoff of 8.7 FU/3 mL was 61.9% and 75.0%, respectively. Increasing the cutoff to 1.5 times (13.1 FU/3 mL) and 2 times (17.4 FU/3 mL) improved the specificity to 90.8% and 95.6%, respectively. The combination of FR+CTCs with WBC, procalcitonin, and LDH resulted in an area under the curve of 0.976 [95% confidence interval (CI): 0.910-1.000], a sensitivity of 100.0%, and a specificity of 85.7%. FR+CTC was proven to be a viable blood biomarker for aiding in the early detection of lung cancer. The combined model based on FR+CTC showed substantially greater accuracy than did any single biomarker in patients with pulmonary nodules.

CT-based radiomics analysis for prediction of pathological subtypes of lung adenocarcinoma

ObjectiveLung cancer is a leading cause of cancer-related deaths worldwide, and its early and accurate diagnosis is crucial for improving patient survival. This paper developed an artificial intelligence (AI) model based on machine learning combined with radiomics for predicting the pathologic type of ground glass nodules (GGN). It explored its potential and challenges in practical applications. MethodsA total of 179 GGN patients with postoperative pathologically confirmed lung adenocarcinoma from June 2022 to June 2024 were collected from a hospital, including 22 cases of atypical adenomatous hyperplasia (AAH), 61 cases of adenocarcinoma in situ (AIS), 55 cases of invasive adenocarcinoma (IAC), and 41 cases of minimally invasive adenocarcinoma (MIA). Two experienced radiologists outlined the imaging data's regions of interest (ROI). Radiomic features were extracted and selected through normalization, mutual information, Spearman correlation coefficient, recursive feature elimination, and LASSO regression. Different machine learning models were developed and the best model was determined based on classification accuracy. ResultsDifferent machine learning models were trained and tested, and a variety of deep learning models were selected for comparison, among which Random Forest had the highest accuracy of 83.3%, and the AUC value of 0.892(95%CI, 0.846-0.923) in recognizing lung adenocarcinoma types. The AUC values reached 0.92 and 0.94 respectively in diagnosing AIS and IAC. ConclusionRadiomics combined with machine learning models, such as Random Forest, outperform average physician diagnostic accuracy in identifying lung adenocarcinoma types. The model is valuable for early and precise lung adenocarcinoma diagnosis, enhancing clinical decision-making.

Endoscopic Endonasal Approach for Calcified Sellar/Parasellar Region Pathologies: Report of 11 Pituitary Adenoma Cases

Calcification in pituitary adenomas is a rare occurence and its differential diagnosis typically includes other sellar masses.Common calcifications in pituitary adenomas are classified into two morphological forms: capsular(eggshell-like)and multiple small nodular calcifications located within the adenoma.Also,there is a pituitary stone term.This study aims to present the results of calcified pituitary adenoma case series who underwent endoscopic endonasal approach(EEA)and the clinical,histopathological characteristics and surgical outcomes of these cases. This study conducted a retrospective cohort analysis of patients with calcified pituitary adenoma operated on by EEA between August 1997 and February 2024.The inclusion criteria were as follows:proven radiological calcification on pre-operative neuroimaging,intraoperative findings of calcification and definitive histopathological diagnosis of calcification.Among these patients,11 cases were included. The mean follow-up duration was 51.45±37.24 (6-118)months.Based on the pre-operative paranasal sinus computed tomography(CT)scans of patients,nine patients(81.8%)had intratumoral calcification,one(9.1%)had capsular(eggshell like)calcification and one(9.1%)had both intratumoral and capsular calcification.Moreover,stone-like calcifications were observed in four patients(36.4%),soft type calcifications in three(27.3%),hard-type calcifications in three(27.3%)and soft and hard-type calcifications in one(9%).Gross total resection(GTR)was achieved in nine patients(81.8%).Pathologic subtypes included non-functioning(n = 4),prolactin secreting(n = 3),growth hormone secreting adenoma(n = 2)and pituitary apoplexy(n = 2).Ten patients had psammomatous type calcifications and one had extensive ossification and osteoid metaplasia. Pre-operative radiological evaluation,intraoperative classification of calcification,and post-operative histopathological assessments are crucial in the treatment of calcified adenomas.Bases on these findings,the EEA,with its advantages,is an approach that can be effectively used in the management of these calcified adenomas.

Causal Association Between Monounsaturated Fatty Acids and Lung Cancer: A Two-Sample Mendelian Randomization Study.

This study aims to investigate the potential causal relationship between monounsaturated fatty acids (MUFAs) and lung cancer. Genetic data on MUFAs and pathological subtypes of lung cancer were extracted from genome-wide association studies (GWAS). The primary analysis utilized inverse-variance weighted analysis (IVW), with additional methods including the weighted median method, MR-Egger regression method, and weighted model method. Sensitivity analysis was conducted to assess the robustness of the findings. The inverse variance-weighted (IVW) analysis of monounsaturated fatty acids in relation to lung adenocarcinoma yielded an odds ratio (OR) of 1.059 with a 95% confidence interval of 0.960 to 1.168 and a p value of 0.252. Similarly, for lung squamous cell carcinoma, the IVW analysis produced odd ratios of 0.884, 95% confidence intervals of 0.747 to 1.045, and a p value of 0.148. In the case of small cell lung cancer, the odds ratio was 0.936, the 95% confidence interval was 0.751 to 1.166, and the p value was 0.554. It can be concluded that there is no direct causal relationship between monounsaturated fatty acids and the development of lung cancer.

A case report of an individual with Creutzfeldt–Jakob disease characterized by prolonged isolated thalamic lesions and rare MM2-cortical-type pathology

BackgroundDiffusion-weighted magnetic resonance imaging (DWI) is essential for diagnosing Creutzfeldt–Jakob disease (CJD). Thalamic lesions are rarely detected by DWI in sporadic CJD (sCJD) cases with methionine homozygosity at polymorphic codon 129 (129MM) of the prion protein (PrP) gene. Here, we describe an unusual sCJD case, characterized by prolonged isolated thalamic diffusion hyperintensities and atypical brain pathology, in combination with the 129MM genotype.Case presentationA 72-year-old Japanese man developed a mild unsteady gait that had persisted for 1 year. DWI revealed isolated thalamic diffusion hyperintensities. Over the following 4 years, his condition progressed to include ataxia and cognitive decline. Repeated cerebrospinal fluid tests were negative for 14-3-3 protein, total tau protein, and real-time quaking-induced conversion assay. Electroencephalography did not show periodic sharp wave complexes or generalized periodic discharges. Despite these findings, thalamic DWI abnormalities persisted and evolved to include cortical lesions in the later stage of the disease. Genetic testing confirmed a 129MM genotype with no pathogenic PrP gene variants. Brain autopsy identified type 2 pathogenic PrP and the absence of the M2-thalamic prion strain, suggesting an MM2-cortical (MM2C)-subtype of sCJD. Histopathology revealed small vacuoles (sv) and patchy-perivacuolar PrP deposits without large vacuoles (lv). Patchy-perivacuolar deposits are a characteristic feature of the MM2C (lv) subtype and indicate MM2C (lv) pathology. Thus, this case was classified as a rare MM2C (sv + lv) subtype. No PrP protein staining was observed in the thalamus, despite spongiform changes with small vacuoles.ConclusionsThis case underscores the diagnostic challenges of atypical CJD with isolated thalamic abnormalities on DWI. Despite negative cerebrospinal fluid findings and clinical diagnostic criteria, persistent DWI abnormalities and evolving clinical symptoms continued to raise suspicion of CJD. A definitive diagnosis, being the MM2C (sv + lv) subtype of sCJD, was confirmed upon pathological examination. Even when atypical findings, such as isolated thalamic abnormalities, are observed and various tests are negative, if suspicion of CJD cannot be ruled out, it is important to confirm the diagnosis and pathological subtypes via postmortem analysis.

Comparison of 18F-FDG and 68Ga-DOTATATE PET/CT in surgically treated lung carcinoid tumors

Aims: This study aims to compare the efficacy of FDG-18 PET/CT and 68Ga-DOTATATE PET/CT imaging techniques in patients with lung carcinoid tumors, identifying the most appropriate preoperative nuclear medicine technique for diagnosis and staging. Methods: We retrospectively analyzed data from 123 patients who underwent surgery for lung carcinoid tumors at our center between 2009 and 2021. All of the patients were scanned with FDG-18 PET/CT before surgery. In addition to FDG-18 PET/CT, 68Ga-DOTATATE PET/CT scanning was performed in 28 patients: 17 in the preoperative and 11 in the postoperative period. Demographic data, mean higher maximal standard uptake (SUVmax) values of primary mass, lymph nodes and extrathoracic foci, pathologic subtype, and type of surgery were recorded. Compliance with normal distribution for numerical data was assessed using the Shapiro-Wilk test. The Wilcoxon signed-rank test was employed for groups meeting normal distribution to compare continuous numerical variables. The Mann-Whitney U and Kruskal-Wallis tests were used when normal distribution assumptions were unsatisfied. Results: The mean SUVmax value in 68Ga-DOTATATE PET/CT was significantly higher than FDG-18 PET/CT in patients with a lung carcinoid tumor (20 vs 4.4). For 68Ga-DOTATATE PET/CT scan, typical carcinoids had higher mean SUVmax value than atypical carcinoids (26 and 5.6 respectively), and the difference was statistically significant (p=0.002). For that FDG18 PET/CT, on the contrary, the mean SUVmax value was higher in atypical carcinoids than typical carcinoids (5.4 and 3.8, respectively), and the difference was not significant (p=0.126) Conclusion: The SUVmax values from 68Ga-DOTATATE PET/CT and FDG-18 PET/CT in lung carcinoid tumors vary by tumor subtype. 68Ga-DOTATATE PET/CT demonstrates higher SUVmax values in typical carcinoid tumors, indicating its superiority over FDG-18 PET/CT for this subtype. Although 68Ga-DOTATATE PET/CT also shows elevated SUVmax in atypical carcinoid tumors, the difference compared to FDG-18 PET/CT does not reach statistical significance.

Effect of POD24 on the prognosis of follicular and other indolent B-cell non-hodgkin lymphomas.

Indolent B-cell non-Hodgkin lymphomas(B-NHL) encompass a heterogeneous category of lymphomas characterized by a wide range of pathological subtypes. With the application of chemoimmunotherapy with rituximab (R-chemo), the prognosis of patients has improved considerably, with a 10-year survival rate of 60-80%. Despite these advancements, a significant number of patients still experience disease progression during or shortly after initial treatment. Those who progress within the first 24 months (POD24) continue to face a notably worse prognosis. This study aims to explore the significance of POD24 in predicting the prognosis of different subtypes of indolent B-cell NHL through a comprehensive literature review. The investigation extends to examining the existing prognostic assessment tools and evaluating the interrelationship between POD24 and these tools. By synthesizing relevant research findings, this study seeks to contribute to the current understanding of the role POD24 plays in prognostic evaluation and its potential implications in guiding clinical decision-making for patients with indolent B-cell NHL.

GPD1L may inhibit the development of esophageal squamous cell carcinoma through the PI3K/AKT signaling pathway: bioinformatics analysis and experimental exploration.

Esophageal squamous carcinoma (ESCC) is the most prevalent pathological subtype of esophageal cancer (EC). It has the characteristics of significant local invasion, quick disease progression, high recurrence rates, and a dismal prognosis for survival. Phosphatidylinositol 3-kinase/serine-threonine kinase (PI3K/AKT) is a signaling system whose aberrant activation regulates downstream factors, leading to the promotion of cancer development. This study looks at a protein called Glycerol-3-phosphate dehydrogenase 1-like (GPD1L), which strongly affects the development of several cancers. However, its association with ESCC development and its underlying mechanisms are not clear. In this paper, we analyzed six ESCC transcriptome data obtained from the GEO database. We utilized bioinformatics technology and immunohistochemistry to differentially analyze GPD1L levels of mRNA and protein expression in ESCC and normal adjacent tissues. Furthermore, we conducted survival, co-expression, enrichment, immune infiltration and drug sensitivity analysis. Moreover, we further investigated the role and mechanism of GPD1L by Western Blot (WB), Cell Counting Kit-8 (CCK8), wound healing assay, Transwell assay, and flow cytometry. Finally, the addition of IGF-1, the activator of PI3K/AKT, could rescue the inhibitory effect of GPD1L on ESCC. The findings manifest that the expression of GPD1L was low in ESCC, and functional experiments showed that GPD1L promoted apoptosis in vitro while blocking cell migration, invasion, and proliferation. Based on mechanism research, GPD1L's impact on ESCC could be explained by its suppression of the PI3K/AKT signaling pathway's activation. To sum up, our findings imply that GPD1L may impede the initiation and advancement of ESCC via modulating the PI3K/AKT signaling pathway. GPD1L is considered to be a promising therapeutic target and biomarker to diagnose and treat ESCC.