Spatial network characteristics and economic effects of element flow in the Lanxi urban agglomeration.

The spatial characteristics of element flow and its spillover are important topics in economics, sociology, and geography, and significant to the promotion of the coordinated development of urban agglomerations. To study element flow in the Lanxi urban agglomeration and its effect to economic development, the spatial network characteristics and economic spillover effect were studied using the methods of spatial network analysis, the spatial Durbin model, and spatial effect decomposition. The results showed that (1) the scale of element flow in the Lanxi urban agglomeration is in an unbalanced distribution state, the scale of element flow in Lanzhou and Xining is higher than that in surrounding cities, and the connection between surrounding cities is also higher than that between other cities; (2) the network structure of element flow in the Lanxi urban agglomeration is relatively intensive, with Lanzhou and Xining as the center of element concentration, which indicates an obvious 'center periphery' structure, and gradually spreads from the core area to the surrounding areas; and (3) the element concentration level of the Lanxi urban agglomeration has a significant positive spillover effect, which plays a significant role in driving the development of surrounding cities. Other factors, such as the social consumption level, have significant direct effects, whereas the industrial structure and residents' income have significant direct and spillover effects, and are the main factors that affect the coordinated development of the regional economy.

[Clinical Application of Microwave Ablation in Potentially Resectable Colorectal Cancer With Simultaneously Multiple Liver Metastases].

Objective To analyze the clinical efficacy of microwave ablation in the colorectal cancer with simultaneously multiple liver metastases that was initially evaluated as potentially resectable. Methods The patients with potentially resectable colorectal cancer with simultaneous multiple liver metastases treated in the Department of General Surgery of the First Affiliated Hospital of Hebei North University,the Center of Minimally Invasive Therapy in Oncology of Traditional Chinese and Western Medicine in Dongzhimen Hospital of Beijing University of Chinese Medicine,and the Second Department of General Surgery in the Fourth Hospital of Hebei Medical University from October 1,2018 to October 1,2020 were selected in this study.The general data,pathological features,treatment methods,and clinical efficacy of the patients were collected.According to the treatment methods,the patients were assigned into a surgical resection group(conversion therapy+laparoscopic primary resection+hepatectomy)and a microwave ablation group(conversion therapy+laparoscopic primary resection+microwave ablation).The surgical indicators(operation duration,time to first postoperative anal exhaust,hospital stay,etc.)and postoperative complications(anastomotic stenosis,anastomotic hemorrhage,incision infection,etc.)were compared between the two groups.The survival period was followed up,including the overall survival period and disease-free survival period,and the survival curves were drawn to analyze the clinical efficacy of the two treatment regimens. Results A total of 198 patients with potentially resectable colorectal cancer with simultaneous multiple liver metastases were included in this study.Sixty-six patients were cured by neoadjuvant chemotherapy(FOLFOX or FOLFIRI),including 30 patients in the surgical resection group and 36 patients in the microwave ablation group(with 57 tumors ablated).After the first ablation,54(94.74%)tumors achieved complete ablation,and all of them reached no evidence of disease status after re-ablation.The microwave ablation group had shorter operation duration,less intraoperative blood loss,shorter time to first postoperative anal exhaust,shorter time of taking a liquid diet,shorter hospital stay,and lower hospitalization cost than the surgical resection group(all P<0.001).In addition,the microwave ablation group had lower visual analogue scale score(P<0.001)than the surgical resection group.The incidences of complications such as incision infection(P=0.740),anastomotic fistula(P=1.000),and anastomotic stenosis(P=1.000),the overall survival period(P=0.191),and the disease-free survival period(P=0.934)showed no significant differences between the two groups. Conclusions For patients with colorectal cancer with simultaneous multiple liver metastases initially assessed as potentially resectable,laparoscopic primary resection+surgical resection/microwave ablation after conversion therapy was safe,effective,and had similar survival outcomes.Microwave ablation outperformed surgical resection in postoperative recovery,economy,and tolerability,being worthy of clinical promotion.

Circulating soluble CD30 is associated with renal tertiary lymphoid structures and the progression of IgA nephropathy.

BACKGROUND: Renal tertiary lymphoid structures (TLSs) are involved in renal pathology and prognosis of IgA nephropathy (IgAN). CD30 and its ligands participate in the formation of renal TLSs. However, the relationship between circulating CD30 and renal prognosis is unclear. The objective of this study was to evaluate the relationship between circulating CD30 and prognosis in patients with IgAN. METHODS: We conducted a retrospective study including 351 patients with biopsy proved IgAN. We collected clinical and pathologic features at the time of biopsy and recorded renal follow-up outcomes. Circulating CD30 levels in IgAN patients at the time of biopsy were measured via enzyme-linked immunosorbent assay (ELISA). The association between elevated CD30 levels and the composite endpoint (defined as a ≥ 50 % decline in eGFR from baseline, end-stage renal disease, or death) was investigated using Cox regression analysis. RESULTS: During a median follow-up period of 5.12 years, 44 (12.5 %) patients in the cohort reached the composite endpoint. Kaplan-Meier survival curve analysis revealed a significant association between higher circulating CD30 levels and a poorer renal prognosis (log-rank P < 0.001). Cox regression analysis showed that high CD30 was an independent factor for the composite endpoints in multivariable-adjusted models (HR 3.397, 95 % CI: 1.230-9.384, P = 0.018). These associations were also observed in a subgroup of patients with concomitant renal TLSs formation (10.443, 95 % CI: 1.680-65.545, P = 0.012), proteinuria > 1 g/d (HR 12.287, 95 % CI: 1.499-100.711, P = 0.019), and female patients (HR 22.372, 95 % CI: 1.797-278.520, P = 0.016). CONCLUSION: Elevated level of circulating CD30 is an independent risk factor for renal disease progression in patients with IgAN.

The significance of an immunohistochemical marker-based panel in assisting the diagnosis of parathyroid carcinoma.

PURPOSE: Parathyroid carcinoma (PC) is an endocrine malignancy with a poor prognosis. However, the diagnosis of PC is still a difficult problem. A model with immunohistochemical (IHC) staining of 5 biomarkers has been reported from limited samples for the differential diagnosis of PC. In the present study, a series of IHC markers was applied in relatively large samples to optimize the diagnostic model for PC. METHODS: In this study, 44 patients with PC, 6 patients with atypical parathyroid tumors and 57 patients with parathyroid adenomas were included. IHC staining for parafibromin, Ki-67, galectin-3, protein-encoding gene product 9.5 (PGP9.5), E-cadherin, and enhancer of zeste homolog 2 (EZH2) was performed on formalin-fixed, paraffin-embedded tissue samples. The effects of clinical characteristics, surgical procedure, and IHC staining results of tumor tissues on the diagnosis and prognosis of PC were evaluated retrospectively. RESULTS: A logistic regression model with IHC results of parafibromin, Ki-67, and E-cadherin was created to differentiate PC with an area under the curve of 0.843. Cox proportional hazards analysis showed that negative parafibromin staining (hazard ratio: 3.26, 95% confidence interval: 1.28-8.34, P = 0.013) was related to the recurrence of PC. CONCLUSION: An IHC panel of parafibromin, Ki-67 and E-cadherin may help to distinguish PC from parathyroid neoplasms. Among the 6 IHC markers and clinical features examined, the risk factor related to PC recurrence was parafibromin staining loss.

Allocation of Eavesdropping Attacks for Multi-System Remote State Estimation.

In recent years, the problem of cyber-physical systems' remote state estimations under eavesdropping attacks have been a source of concern. Aiming at the existence of eavesdroppers in multi-system CPSs, the optimal attack energy allocation problem based on a SINR (signal-to-noise ratio) remote state estimation is studied. Assume that there are N sensors, and these sensors use a shared wireless communication channel to send their state measurements to the remote estimator. Due to the limited power, eavesdroppers can only attack M channels out of N channels at most. Our goal is to use the Markov decision processes (MDP) method to maximize the eavesdropper's state estimation error, so as to determine the eavesdropper's optimal attack allocation. We propose a backward induction algorithm which uses MDP to obtain the optimal attack energy allocation strategy. Compared with the traditional induction algorithm, this algorithm has lower computational cost. Finally, the numerical simulation results verify the correctness of the theoretical analysis.

Development and validation of a nomogram model based on pretreatment ultrasound and contrast-enhanced ultrasound to predict the efficacy of neoadjuvant chemotherapy in patients with borderline resectable or locally advanced pancreatic cancer.

OBJECTIVES: To develop a nomogram using pretreatment ultrasound (US) and contrast-enhanced ultrasound (CEUS) to predict the clinical response of neoadjuvant chemotherapy (NAC) in patients with borderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC). METHODS: A total of 111 patients with pancreatic ductal adenocarcinoma (PDAC) treated with NAC between October 2017 and February 2022 were retrospectively enrolled. The patients were randomly divided (7:3) into training and validation cohorts. The pretreatment US and CEUS features were reviewed. Univariate and multivariate logistic regression analyses were used to determine the independent predictors of clinical response in the training cohort. Then a prediction nomogram model based on the independent predictors was constructed. The area under the curve (AUC), calibration plot, C-index and decision curve analysis (DCA) were used to assess the nomogram's performance, calibration, discrimination and clinical benefit. RESULTS: The multivariate logistic regression analysis showed that the taller-than-wide shape in the longitudinal plane (odds ratio [OR]:0.20, p = 0.01), time from injection of contrast agent to peak enhancement (OR:3.64; p = 0.05) and Peaktumor/ Peaknormal (OR:1.51; p = 0.03) were independent predictors of clinical response to NAC. The predictive nomogram developed based on the above imaging features showed AUCs were 0.852 and 0.854 in the primary and validation cohorts, respectively. Good calibration was achieved in the training datasets, with C-index of 0.852. DCA verified the clinical usefulness of the nomogram. CONCLUSIONS: The nomogram based on pretreatment US and CEUS can effectively predict the clinical response of NAC in patients with BRPC and LAPC; it may help guide personalized treatment.

The tumoral microbiome of pancreatic intraductal papillary mucinous neoplasm: A single-center retrospective cohort study.

BACKGROUND AND AIM: Pancreatic intraductal papillary mucinous neoplasm (IPMN) is one of the most common precancerous lesions of pancreatic carcinoma. Studies have found that the tumoral microbiome has an important influence on pancreatic carcinoma. However, the tumoral microbiome of IPMNs has rarely been explored. METHODS: Tumoral microbiome gene sequencing was carried out using 16 specimens of IPMN and 45 specimens of IPMN with associated invasive carcinoma (IPMN-IC) by 2bRAD sequencing for microbiome. The profile of the tumoral microbiome was summarized. Associations of the tumoral microbiome with disease grade, histological subtype, and prognosis were analyzed. RESULTS: A total of 598 species of microbes were identified, comprising 228 genera, 109 families, 60 orders, 29 classes, 14 phyla, and 2 kingdoms. The genus Pseudomonas was detected more frequently and had higher relative abundance in IPMN-ICs; Alcaligenes faecalis was detected with higher relative abundance in IPMNs. Bifidobacterium pseudolongum had a higher relative abundance in the IPMN-IC group, regardless of histological subtype. Moreover, among patients with IPMN-ICs, those with a high relative abundance of B. pseudolongum had better overall survival than those with a low relative abundance. Patients who were positive for Staphylococcus aureus or Mycolicibacillus koreensis had shorter survival. The presence of S. aureus was an independent risk factor for poor prognosis. CONCLUSIONS: There are enriching tumoral microbes in IPMN. The tumoral microbiome of IPMN is different from that of IPMN-IC.

Evaluation of the diagnostic efficacy of liquid-based cytology obtained via percutaneous ultrasound-guided fine-needle aspiration for pancreatic masses: a large tertiary center's 8-year experience.

PURPOSE: There were limited data on the diagnostic efficacy of liquid-based cytology (LBC) for pancreatic tissues acquired by percutaneous ultrasound-guided fine-needle aspiration (US-FNA). This study aimed to evaluate the diagnostic value of LBC acquired via percutaneous US-FNA for pancreatic tumors compared with LBC combined with smear cytology (SC). METHODS: A retrospective database search (January 2014 and February 2022) was performed for patients who underwent percutaneous US-FNA with both LBC and SC. Clinical and pathological data were collected from 298 patients; eventually, 251 cases met the inclusion criteria. Diagnostic accuracy, sensitivity (SEN), specificity (SPE), positive predictive value (PPV) and negative predictive value (NPV) were compared. Rapid on-site evaluation (ROSE) was not available in all cases. RESULTS: Based on the pancreaticobiliary cytology guidelines published by the Papanicolaou Society of Cytopathology, 224 (89.2%), 13 (5.2%) and 14 (5.6%) cases were diagnosed as malignant, pre-malignant and benign lesions, respectively. The diagnostic accuracy of the LBC + SC (88.5%) was better than that of LBC (87.3%) but without statistical significance (P = 0.125). The SEN, SPE, PPV and NPV were 87.5%, 85.2%, 98.0% and 45.1%, respectively, in the LBC group and 88.8%, 85.2%, 98.0% and 47.9%, respectively, in the LBC + SC group. According to univariate and multivariate analyses, there were no factors have significant association with the diagnostic sensitivity of LBC. CONCLUSIONS: LBC obtained via percutaneous US-FNA provides good diagnostic value for pancreatic lesions and there was no significant difference between the diagnostic accuracy of LBC and LBC + SC when ROSE was unavailable.

The mechanism of linear ubiquitination in regulating cell death and correlative diseases.

Linear ubiquitination is a specific post-translational modification in which ubiquitin is linked through M1 residue to form multiple types of polyubiquitin chains on substrates in order to regulate cellular processes. LUBAC comprised by HOIP, HOIL-1L, and SHARPIN as a sole E3 ligase catalyzes the generation of linear ubiquitin chains, and it is simultaneously adjusted by deubiquitinases such as OTULIN and CYLD. Several studies have shown that gene mutation of linear ubiquitination in mice accompanied by different modalities of cell death would develop relative diseases. Cell death is a fundamental physiological process and responsible for embryonic development, organ maintenance, and immunity response. Therefore, it is worth speculating that linear ubiquitin mediated signaling pathway would participate in different diseases. The relative literature search was done from core collection of electronic databases such as Web of Science, PubMed, and Google Scholar using keywords about main regulators of linear ubiquitination pathway. Here, we summarize the regulatory mechanism of linear ubiquitination on cellular signaling pathway in cells with apoptosis, necroptosis, autophagy, pyroptosis, and ferroptosis. Intervening generation of linear ubiquitin chains in relative signaling pathway to regulate cell death might provide novel therapeutic insights for various human diseases.

Immunogenic cell death-based prognostic model for predicting the response to immunotherapy and common therapy in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is a malignant tumor in the respiratory system. The efficacy of current treatment modalities varies greatly, and individualization is evident. Therefore, finding biomarkers for predicting treatment prognosis and providing reference and guidance for formulating treatment options is urgent. Cancer immunotherapy has made distinct progress in the past decades and has a significant effect on LUAD. Immunogenic Cell Death (ICD) can reshape the tumor's immune microenvironment, contributing to immunotherapy. Thus, exploring ICD biomarkers to construct a prognostic model might help individualized treatments. We used a lung adenocarcinoma (LUAD) dataset to identify ICD-related differentially expressed genes (DEGs). Then, these DEGs were clustered and divided into subgroups. We also performed variance analysis in different dimensions. Further, we established and validated a prognostic model by LASSO Cox regression analysis. The risk score in this model was used to evaluate prognostic differences by survival analysis. The treatment prognosis of various therapies were also predicted. LUAD samples were divided into two subgroups. The ICD-high subgroup was related to an immune-hot phenotype more sensitive to immunotherapy. The prognostic model was constructed based on six ICD-related DEGs. We found that high-risk score patients responded better to immunotherapy. The ICD prognostic model was validated as a standalone factor to evaluate the ICD subtype of individual LUAD patients, which might contribute to more effective therapies.

Identification of immunotherapy biomarkers for improving the clinical outcome of homologous recombination deficiency patients with lung adenocarcinoma.

Homologous recombination deficiency (HRD) is a common molecular signature of genomic instability and has been shown to be a biomarker for targeted therapies. However, there is a lack of studies on the role of HRD changes in lung adenocarcinoma (LUAD) transcriptomics. HRD scores were determined using single nucleotide polymorphism (SNP) array data from LUAD patients from The Cancer Genome Atlas (TCGA) database. Transcriptional data from patients with different scores were analyzed to identify biomarkers associated with HRD. Candidate biomarkers were validated using Gene Expression Omnibus (GEO)-sourced datasets and an immunotherapy cohort. According to the bulk transcriptome and clinical characteristics of 912 LUAD patients and Single-cell RNA-seq of 9 LUAD patients from TCGA and GEO databases, we observed increased MS4A6A expression in HRD tumors; high MS4A6A expression predicted improved survival outcomes. Furthermore, a comprehensive analysis of the tumor immune microenvironment (TIME) revealed a positive correlation between MS4A6A expression and neoantigen loading and immune cell infiltration. Additionally, the immunotherapy cohort confirmed the possibility of using MS4A6A as a biomarker. Collectively, we suggest that MS4A6A is associated with HRD and provide a new perspective toward identifying promising biomarkers for immunotherapy.

Clinicopathological analysis of patients with molecularly confirmed stage I adult granulosa cell tumors and prediction of recurrence.

OBJECTIVE: Adult granulosa cell tumors (AGCTs) are rare malignancies that accounts for approximately 1% of ovarian neoplasms. As there are currently no well-recognized models for predicting relapse-free survival (RFS), we performed a clinicopathological analysis to identify risk factors for AGCT recurrence. METHODS: We investigated 130 patients with pathologically diagnosed AGCT as confirmed by the presence of the characteristic FOXL2 C402G mutation. RESULTS: Most patients had International Federation of Gynecology and Obstetrics stage I disease (n = 122, 95.3%). The 10-year RFS rate was 31.4% (22/70) and mean 10-year RFS was 74.4 (95% CI, 65.2-83.7) months. Ten patients experienced recurrence beyond the 10-year follow-up period. Undergoing fertility sparing surgery, an estrogen receptor-α (ERα) score (>0.25), and a Ki-67 index >15% were independent risk factors for recurrence in patients with stage I disease (bias-corrected C-index: 0.776). We constructed a nomogram with well-fitting calibration plots; the areas under the curve (AUCs) for 5-, and 10-year RFS prediction were 0.883 and 0.906 respectively. A simplified model with 3 predictive factors (ERα score, Ki-67 index, and primary surgical procedure) and 2 risk stratification subgroups (low- and high-risk) was constructed; its AUCs for 5-, and 10-year RFS prediction were 0.825 and 0.850 respectively. Kaplan-Meier survival curves showed significant differences in 10-year RFS between the low- and high-risk groups (p < 0.001). CONCLUSIONS: The type of primary surgical procedure, ERα score, and Ki-67 index are independent predictors of recurrence for patients with stage I AGCT. Our predictive model based on these factors showed good performance.

Development and validation of a nomogram for predicting overall survival of resected N2 non-small cell lung cancer patients undergoing neoadjuvant radiotherapy.

INTRODUCTION: Currently, the prognosis of resected N2 non-small cell lung cancer patients undergoing neoadjuvant radiotherapy is poor. The goal of this research was to develop and validate a novel nomogram for exactly predicting the overall survival (OS) of resected N2 NSCLC patients undergoing neoadjuvant radiotherapy. METHODS: The data applied in our research were downloaded from the Surveillance, Epidemiology, and End Results (SEER) database. We divided selected data into a training cohort and a validation cohort using R software, with a ratio of 7:3. Univariate Cox regression and multivariate Cox regression were utilized to select significant variables to build the nomogram. To validate our nomogram, calibration curves, receiver operating characteristic curves (ROC), decision curve analysis (DCA), and Kaplan-Meier survival curves were employed. The nomogram model was also compared with the tumor-node-metastasis (TNM) staging system by utilizing net reclassification index (NRI) and integrated discrimination improvement (IDI). RESULTS: Eight variables-age, sex, operative type, LN removed number, chemotherapy, AJCC stage, M stage, histology-were statistically significant in the multivariate Cox regression analysis and were selected to develop our nomogram. Based on ROC curves, calibration curves, and DCA analysis, our novel nomogram demonstrated good predictive accuracy and clinical utility. Using Kaplan-Meier (KM) survival curves and log-rank tests, the risk stratification system was able to stratify patients based on their estimated mortality risk. The nomogram performed better than the TNM staging system based on the NRI and IDI indexes. CONCLUSIONS: We developed and validated a nomogram to predict prognosis of resected N2 NSCLC patients undergoing neoadjuvant radiotherapy. Using this nomogram, clinicians may find this nomogram useful in predicting OS of targeted patients and making more appropriate treatment decisions.

An anoikis-based gene signature for predicting prognosis in malignant pleural mesothelioma and revealing immune infiltration.

INTRODUCTION: Malignant pleural mesothelioma (MPM) is an aggressive, treatment-resistant tumor. Anoikis is a particular type of programmed apoptosis brought on by the separation of cell-cell or extracellular matrix (ECM). Anoikis has been recognized as a crucial element in the development of tumors. However, few studies have comprehensively examined the role of anoikis-related genes (ARGs) in malignant mesothelioma. METHODS: ARGs were gathered from the GeneCard database and the Harmonizome portals. We obtained differentially expressed genes (DEGs) using the GEO database. Univariate Cox regression analysis, and the least absolute shrinkage and selection operator (LASSO) algorithm were utilized to select ARGs associated with the prognosis of MPM. We then developed a risk model, and time-dependent receiver operating characteristic (ROC) analysis and calibration curves were employed to confirm the ability of the model. The patients were divided into various subgroups using consensus clustering analysis. Based on the median risk score, patients were divided into low- and high-risk groups. Functional analysis and immune cell infiltration analysis were conducted to estimate molecular mechanisms and the immune infiltration landscape of patients. Finally, drug sensitivity analysis and tumor microenvironment landscape were further explored. RESULTS: A novel risk model was constructed based on the six ARGs. The patients were successfully divided into two subgroups by consensus clustering analysis, with a striking difference in the prognosis and landscape of immune infiltration. The Kaplan-Meier survival analysis indicated that the OS rate of the low-risk group was significantly higher than the high-risk group. Functional analysis, immune cell infiltration analysis, and drug sensitivity analysis showed that high- and low-risk groups had different immune statuses and drug sensitivity. CONCLUSIONS: In summary, we developed a novel risk model to predict MPM prognosis based on six selected ARGs, which could broaden comprehension of personalized and precise therapy approaches for MPM.

Pancreatic ductal adenocarcinoma with synchronous and metachronous hepatic metastasis predicted by contrast-enhanced ultrasound.

Background: Contrast-enhanced ultrasound (CEUS) has proven valuable in diagnosing benign and malignant pancreatic diseases, but its value in evaluating hepatic metastasis remains to be further explored. This study investigated the relationship between CEUS features of pancreatic ductal adenocarcinoma (PDAC) and concomitant or recurrent liver metastases after treatment. Methods: This retrospective study included 133 participants with PDAC who were diagnosed with pancreatic lesions with CEUS at Peking Union Medical College Hospital from January 2017 to November 2020. According to the CEUS classification methods in our center, all the pancreatic lesions were classified as either with rich or poor blood supply. Additionally, quantitative ultrasonographic parameters were measured in the center and periphery of all pancreatic lesions. CEUS modes and parameters of the different hepatic metastasis groups were compared. The diagnostic performance of CEUS was calculated for diagnosing synchronous and metachronous hepatic metastasis. Results: The proportions of rich blood supply and poor blood supply were 46% (32/69) and 54% (37/69), respectively, in the no hepatic metastasis group; 42% (14/33) and 58% (19/33), respectively, in the metachronous hepatic metastasis (MHM) group; and 19% (6/31) and 81% (25/31), respectively, in the synchronous hepatic metastasis (SHM) group. The wash-in slope ratio (WIS ratio) between the center of the lesion and around the lesion and peak intensity ratio (PI ratio) between the center of the lesion and around the lesion had higher values in the negative hepatic metastasis group (P<0.05). In predicting synchronous and metachronous hepatic metastasis, the WIS ratio had the best diagnostic performance. The sensitivity (SEN), specificity (SPE), accuracy (ACC), positive predictive value (PPV), and negative predictive value (NPV) were 81.8%, 95.7%, 91.2%, 90.0%, and 91.7%, respectively, for MHM; and 87.1%, 95.7%, 93.0%, 90.0%, and 94.3%, respectively, for SHM. Conclusions: CEUS would be helpful in image surveillance for synchronous or metachronous hepatic metastasis of PDAC.

Expression of PD-L1 and VISTA in Intraductal Papillary Mucinous Neoplasm With Associated Invasive Carcinoma of the Pancreas.

Early detection and treatment of invasive carcinoma arising in association with intraductal papillary mucinous neoplasm (IPMN), which is biologically and (epi)genetically distinct from conventional pancreatic ductal adenocarcinoma, provide an opportunity to improve the prognosis of this lethal disease. Despite the successful application of programmed death (ligand) 1 (PD-[L]1)-blocking strategies in numerous cancers, the immune microenvironment of IPMN with associated invasive carcinoma remains elusive. Here, we investigated CD8+ T cells, CD68+ macrophages, PD-L1, and V-domain immunoglobulin suppressor of T-cell activation (VISTA) in 60 patients with IPMN with associated invasive carcinoma using immunohistochemistry, explored their correlations with clinicopathologic variables and prognosis, and compared them with those in 76 patients with IPMN without invasive carcinoma (60 low-grade and 16 high-grade lesions). Using antibodies against CD8, CD68, and VISTA, we evaluated tumor-infiltrating immune cells in 5 high-power fields (×400) and calculated the corresponding mean counts. PD-L1 with a combined positive score of ≥1 was regarded as positive, and VISTA expression on tumor cells (TCs) was deemed positive when ≥1% of TCs showed membranous/cytoplasmic staining. A reduction of CD8+ T cells and an increase of macrophages were observed during carcinogenesis. Positive PD-L1 combined positive score and VISTA expression on TCs were 13% and 11% in the intraductal component of IPMN with associated invasive carcinoma, 15% and 12% in the associated invasive carcinoma, and 6% and 4% in IPMN without an invasive carcinoma, respectively. Interestingly, the PD-L1 positivity rate was the highest in a subset of associated invasive carcinomas (predominantly gastric-type-derived) and was associated with higher counts of CD8+ T cells, macrophages, and VISTA+ immune cells. Accumulation of VISTA+ immune cells was observed in the intraductal component of IPMN with associated invasive carcinoma compared with that of low-grade IPMN, whereas in intestinal-type IPMN with associated invasive carcinoma, the number of these cells decreased during the transition from the intraductal component to the associated invasive carcinoma. Survival analysis revealed that a higher number of macrophages predicted poorer prognosis. In conclusion, our results might help in individualized immunotherapeutic strategies for these patients.

Preoperative computed tomography-based tumoral radiomic features prediction for overall survival in resectable non-small cell lung cancer.

Objectives: The purpose of this study was to evaluate whether preoperative radiomics features could meliorate risk stratification for the overall survival (OS) of non-small cell lung cancer (NSCLC) patients. Methods: After rigorous screening, the 208 NSCLC patients without any pre-operative adjuvant therapy were eventually enrolled. We segmented the 3D volume of interest (VOI) based on malignant lesion of computed tomography (CT) imaging and extracted 1542 radiomics features. Interclass correlation coefficients (ICC) and LASSO Cox regression analysis were utilized to perform feature selection and radiomics model building. In the model evaluation phase, we carried out stratified analysis, receiver operating characteristic (ROC) curve, concordance index (C-index), and decision curve analysis (DCA). In addition, integrating the clinicopathological trait and radiomics score, we developed a nomogram to predict the OS at 1 year, 2 years, and 3 years, respectively. Results: Six radiomics features, including gradient_glcm_InverseVariance, logarithm_firstorder_Median, logarithm_firstorder_RobustMeanAbsoluteDeviation, square_gldm_LargeDependenceEmphasis, wavelet_HLL_firstorder_Kurtosis, and wavelet_LLL_firstorder_Maximum, were selected to construct the radiomics signature, whose areas under the curve (AUCs) for 3-year prediction reached 0.857 in the training set (n=146) and 0.871 in the testing set (n=62). The results of multivariate analysis revealed that the radiomics score, radiological sign, and N stage were independent prognostic factors in NSCLC. Moreover, compared with clinical factors and the separate radiomics model, the established nomogram exhibited a better performance in predicting 3-year OS. Conclusions: Our radiomics model may provide a promising non-invasive approach for preoperative risk stratification and personalized postoperative surveillance for resectable NSCLC patients.

Solid Pseudopapillary Neoplasms of the Pancreas: Clinicopathologic Analysis and a Predictive Model.

Solid pseudopapillary neoplasms (SPNs) of the pancreas are rare. They are considered low-grade malignancies, and a small percentage of patients experience recurrence or metastasis. It is critical to investigate associated biological behavior and identify patients at a risk of relapse. This was a retrospective study of 486 patients with SPNs who were diagnosed between 2000 and 2021. Their clinicopathologic features, including 23 parameters and prognoses were analyzed. Six patients (1.2%) presented with synchronous liver metastasis. A total of 21 patients experienced recurrence or metastasis postoperatively. The overall and disease-specific survival rates were 99.8% and 100%, respectively. The 5- and 10-year relapse-free survival (RFS) rates were 97.4% and 90.2%, respectively. Tumor size, lymphovascular invasion, and the Ki-67 index were independent predictors of relapse. Furthermore, a Peking Union Medical College Hospital-SPN risk model was built to evaluate the risk of relapse and compared it with the American Joint Committee on Cancer tumor staging system (eighth edition, 2017). Risk factors included 3 parameters: tumor size (>9 cm), lymphovascular invasion status (presence), and Ki-67 index (>1%). Risk grades were available for 345 patients, who were divided into 2 groups: (1) low risk (n = 124) and (2) high risk (n = 221). The group with no risk factors was designated as low risk and had a 10-year RFS of 100%. The group associated with 1 to 3 factors was designated as high risk, with a 10-year RFS of 75.3%. Receiver operating characteristic curves were generated, and the area under the curve was 0.791 for our model and 0.630 for the American Joint Committee on Cancer with respect to the cancer staging system. We validated our model in independent cohorts and demonstrated a sensitivity of 98.3%. In conclusion, SPNs are low-grade malignant neoplasms that rarely metastasize, and the 3 selected pathologic parameters can be used to predict their behavior. A novel Peking Union Medical College Hospital-SPN risk model was proposed for routine application to guide the patient counseling in clinical practice.